PMID- 6239899 TI - Production of target-specific effector cells using hetero-cross-linked aggregates containing anti-target cell and anti-Fc gamma receptor antibodies. AB - Rabbit anti-2,4-dintrophenyl (DNP) antibodies or their F(ab')2 fragments were chemically cross-linked to the anti-mouse Fc gamma R monoclonal antibody 2.4G2 or to its Fab fragment. P388D1 cells were incubated with heteroaggregates between 2.4G2 and anti-DNP (anti-Fc gamma R X anti-DNP) and washed. The resulting cells lysed 2,4,6-trinitrophenyl chicken erythrocytes (TNP CRBC) in a hapten-specific manner. The lysis was inhibited by free hapten but was resistant to inhibition by immune complexes. Other cells coated with antibody heteroaggregates also mediated lysis of TNP-modified target cells. For example, mouse resident peritoneal exudate cells (PEC) lysed TNP CRBC and bacillus Calmette-Guerin-activated PEC lysed both TNP CRBC and TNP tumor targets. Human neutrophils, when incubated with heteroaggregates containing the anti-human neutrophil Fc gamma R antibody 3G8 and anti-DNP also lysed TNP CRBC and TNP-modified tumor cells. To test whether linkage to Fc gamma R was required for lysis, F(ab')2 fragments from the anti KdDd monoclonal antibody 34-1-2 were cross-linked to anti-DNP F(ab')2 fragments. P388D1 cells (which express Kd and Dd) were then incubated with these heteroaggregates and washed, and their abilities to form conjugates and lyse TNP CRBC were compared with those of P388D1 cells treated with anti-Fc gamma R X anti DNP. In both cases, P388D1 cells formed conjugates. However, only the cells treated with anti-Fc gamma R X anti-DNP mediated lysis to a significant extent. We conclude that heteroaggregates containing anti-Fc gamma R and anti-target cell antibodies can be used to create potent effector cells against red cell and tumor targets and that bridging of effectors with target cells directly to Fc gamma R on effector cells is required for lysis. PMID- 6239900 TI - Functional heterogeneity in allospecific cytotoxic T lymphocyte clones. I. CTL clones express strong anti-self suppressive activity. AB - Five out of five allo-specific cytotoxic T lymphocyte (CTL) clones tested strongly suppressed the development of CTLs directed against the H-2 haplotype of the CTL clone and independent of the H-2 specificity recognized by the CTL clone. This was shown by including 100-1,000 cells from the five clones in one way mixed lymphocyte reaction (MLR) cultures in which the stimulator cells were of the same H-2 type as the CTL cells. When these cultures were assayed for cytotoxicity against the stimulator cell haplotype, the cytotoxic activity was decreased in a CTL cell dose-dependent manner by 50 to more than 90%. Suppression was usually not observed in MLR cultures where the CTL-H-2 type was identical with the responder cells or was different from both the responder or stimulator cells. Suppression was demonstrated not to be due to "cold" target inhibition at the time of cytotoxicity assay. Even if the added CTL were completely removed after 48-72 h of culture, significant suppression was obtained. Suppressive ability did not appear to be correlated with the level of allo-specific cytotoxic activity present in the CTL clones, but might involve direct killing of MLR precursor cells by cells in the added CTL clones. The suppression observed here, which is anti-self from the point of view of the added CTL clone, appears to be triggered by precursor cells in the MLR responder population recognizing MHC determinants on cells from the added CTL clone. This peculiar type of suppression, in which the regulator regulates on being recognized, has been christened the veto phenomenon and may play a role in maintenance of self tolerance. PMID- 6239901 TI - Resting and sensitized T lymphocytes exhibit distinct stimulatory (antigen presenting cell) requirements for growth and lymphokine release. AB - Previous studies have shown that unprimed or resting T lymphocytes will grow and release lymphokines when stimulated by dendritic cells (DC). We now have examined the stimulatory requirements for antigen-primed or blast-transformed T cells. The latter were derived from dendritic/T cell clusters that developed during the primary mixed leukocyte reaction (MLR). The specificity of the blasts was established by a binding assay in which most T cells aggregated small B lymphocytes of the appropriate haplotype within 2 h at 4 or 37 degrees C. Since unprimed T cells did not aggregate allogeneic B cells, we suggest that DC induce T lymphocytes to express additional functioning receptors for antigen. Lyt-2-T blasts did not grow or release interleukin 2 or B cell helper factors unless rechallenged with specific alloantigen, whereupon growth (generation time of 14 18 h) and lymphokine release rapidly resumed. The blasts could be stimulated by allogeneic macrophages, B cells, and B lymphoblasts, whereas the primary MLR was initiated primarily by DC. responsiveness appeared restricted to the I region of the major histocompatibility complex, and varied directly with the level of Ia antigens on the stimulator cells. The interaction of B cells and T blasts was bidirectional. The T blasts would grow and form B cell helper factors, while the B cells grew and secreted antibody. However, the efficacy of T cell-mediated antibody formation was enhanced some 10-fold by the addition of specific antigen. Therefore, responses of resting helper T cells, then, are initiated by antigen plus DC. Once sensitized, T blasts interact independently with antigen presented by other leukocytes. PMID- 6239902 TI - In vivo and in vitro characterization of specific hyporeactivity to skin xenografts in mixed xenogeneically reconstituted mice (B10 + F344 rat----B10). AB - Mixed xenogeneically reconstituted mice (F344 rat + C57BL/10Sn----C57BL/10Sn), which specifically retain F344 tail skin xenografts, were studied for the specificity of such hyporeactivity and for in vitro reactivity and immunocompetence. Survival of mixed reconstituted animals was excellent, without evidence for graft vs. host disease. Donor-type tail skin grafts were specifically prolonged (mean survival time = 80 d) in comparison with normal controls and syngeneically reconstituted animals. In vitro, such animals manifested specific hyporeactivity by mixed lymphocyte reaction and cell-mediated lympholysis to F344 rat and B10 cells, with normal response to third-party rat (Wistar-Furth) and mouse (B10.BR). Examination of lymphoid tissues with a fluorescence-activated cell sorter revealed low levels, if any, of donor-type cells detectable. This system offers a model for investigation of xenogeneic transplantation tolerance. PMID- 6239903 TI - Identification of soluble Fc receptors in mouse serum and the conditioned medium of stimulated B cells. AB - We have evaluated the expression of surface Fc gamma 2b/gamma 1R by lipopolysaccharide (LPS)-activated murine spleen cells, the release of soluble Fc gamma 2b/gamma 1R by activated spleen cells, and the presence of circulating Fc gamma 2b/gamma 1R in mouse serum. LPS activation of murine spleen cells and a cloned B cell line, BCL-1 CW 13.20-3B3, resulted in a 5-10-fold increase in surface Fc gamma 2b/gamma 1R and the concominant appearance in the culture medium of a soluble molecule that is antigenically related to the Fc gamma 2b/gamma 1R. The increase in cell-associated and soluble Fc gamma 2b/gamma 1R after LPS activation is attributable primarily to B cells. Circulating Fc gamma 2b/gamma 1R was also detected in normal mouse serum at a concentration of 10(-9) to 10(-8) M. Levels of circulating Fc gamma 2b/gamma 1R increase with the age of the animals, and were low in adult germ-free mice and elevated in young mice with certain autoimmune diseases. The circulating Fc gamma 2b/gamma 1R bound to IgG-Sepharose, and was partially purified by affinity chromatography on 2.4G2 Fab-Sepharose. After radiolabeling and immunoprecipitation with rabbit anti-Fc gamma 2b/gamma 1R serum, one component of Mr 48,000, was detected. PMID- 6239904 TI - Shape and depth perception from parallel projections of three-dimensional motion. AB - Parallel projections of dots on the surface of a transparent sphere rotating about a vertical axis provide strong impressions of depth and spherical shape. The hypothesis was tested that these impressions are the result of three perceptual heuristics: (a) The sinusoidal projected velocity function of each dot in the horizontal dimension tends to be perceived as a rotary motion in depth; (b) the projected velocity gradient in the vertical dimension is perceived as curvature in depth; and (c) the simultaneously visible fields of dots moving in opposite directions are perceived as surfaces separated in depth. When each factor was varied independently, all three significantly affected judgments of spherical shape and depth. Similar results were obtained with cylinders. The first factor was more important for shape judgments; the second was generally more important for depth judgments. These results, together with those of earlier studies in which these factors led to similar effects for different stimuli and transformations, suggest that these are general principles applicable to the perception of structure from both rigid and nonrigid motion. PMID- 6239905 TI - Event-related brain potentials reveal similar attentional mechanisms during selective listening and shadowing. AB - The properties of linguistic attention were examined by recording event-related brain potentials (ERPs) to probe stimuli mixed with dichotically presented prose passages. Subjects either shadowed (repeated phrase by phrase) or selectively listened to one passage while ERPs were recorded from electrodes overlying midline sites, left-hemisphere speech areas, and corresponding areas of the right hemisphere. Mixed with each voice (a male voice in one ear, a female voice in the other) were four probe stimuli: digitized speech sounds (but or /a/ as in father) produced by the same speaker and tone bursts at the mean fundamental and second formant frequencies of that voice. The ERPs elicited by the speech probes in the attended ear showed an enhanced negativity, with an onset at 50 ms-100 ms and lasting up to 800 ms-1,000 ms, whereas the ERPs to the second formant probes showed an enhanced positivity in the 200 ms-300 ms latency range. These effects were comparable for shadowing and selective listening conditions and remained stable over the course of the experiment. The attention-related negativity to the consonant-vowel-consonant probe (but) was most prominent over the left hemisphere; other probes produced no significant asymmetries. The results indicate that stimulus selection during linguistic attention is specifically tuned to speech sounds rather than simply to constituent pure-tone frequencies or ear of entry. Furthermore, it appears that both attentional set and stimulus characteristics can influence the hemispheric utilization of stimuli. PMID- 6239906 TI - Sensitization of the visual field. AB - Three experiments investigated the identification or localization of a letter that was displaced from the fixation point by 1 degree-3 degrees. The subject's task was to identify a fixated letter and identify (Experiment 1) or localize (Experiments 2 and 3) the displaced letter. On uncued trials, the displaced letter could appear at any of eight locations on any of three rings surrounding the fixated letter; on cued trials, the ring containing the displaced letter was specified. The results indicated that cuing improved subjects' identification and localization of the displaced letter. Invalid cuing (Experiment 3) produced costs comparable in magnitude to the benefits. The distance of the target from the cued ring determined cost, but costs were unaffected by the appearance of a target within the presumed beam of attention. It was proposed that attention should be viewed as a general, rather than feature-specific, resource that can be voluntarily allocated to multiple regions of the visual field. PMID- 6239907 TI - Functionally specific articulatory cooperation following jaw perturbations during speech: evidence for coordinative structures. AB - In three experiments we show that articulatory patterns in response to jaw perturbations are specific to the utterance produced. In Experiments 1 and 2, an unexpected constant force load (5.88 N) applied during upward jaw motion for final /b/ closure in the utterance /baeb/ revealed nearly immediate compensation in upper and lower lips, but not the tongue, on the first perturbation trial. The same perturbation applied during the utterance /baez/ evoked rapid and increased tongue-muscle activity for /z/ frication, but no active lip compensation. Although jaw perturbation represented a threat to both utterances, no perceptible distortion of speech occurred. In Experiment 3, the phase of the jaw perturbation was varied during the production of bilabial consonants. Remote reactions in the upper lip were observed only when the jaw was perturbed during the closing phase of motion. These findings provide evidence for flexibly assembled coordinative structures in speech production. PMID- 6239908 TI - A genetic analysis of defective plasmid formation by N-deficient phage lambda chromosomes. AB - Plasmid formation by N- derivatives of lambdoid phages has been reinvestigated with transducing phages carrying the trp, lac and gal genes of Escherichia coli. Transduction by lambda N- cI- derivatives was inefficient and short-lived in each case, under both selective and nonselective conditions. Mutant-operators were introduced to relieve possible auto-repression by the cro gene product. Such N defective phage genomes were able to propagate continually as plasmids, although without selection they were gradually lost from the carrier cells. Plasmid formation remained inefficient, however. The entire chromosome of N- phages can be expressed by transcription that leaks through the serially arranged Rho dependent terminators. Some functions so expressed are deleterious to the plasmid state and cause the instability of lambda N- plasmids. PMID- 6239909 TI - Adenovirus type 12 early region 1 proteins: a study of their subcellular localization and protein-protein interactions. AB - Subcellular fractionation of rat and human cells transformed by the adenovirus type 12 (Ad-12) EcoRI-C DNA fragment showed that the 41000 mol. wt. (41K) E1a and 52K E1b proteins were present in the nucleus and cytoplasm at approximately equal concentrations. The 18K E1b protein was associated with the nuclear, mitochondrial, lysosomal and membrane fractions. The 41K E1a protein was also associated with various cytoskeletal structures (probably microtubules and 10 nm filaments) in Ad-12-transformed cells. The Ad-12 E1 41K and 52K proteins have been partially purified from transformed and infected cells. Using these preparations the 52K protein has been shown to exist under non-reducing conditions and probably in vivo as a 100K dimer stabilized by intermolecular disulphide bonds. The 41K protein bound strongly to histones H1 and H4 but much more weakly to H2A, H2B and H3. It did not interact with other comparable basic proteins or with the cytoskeletal components actin, tropomyosin and calmodulin. Although the 41K E1 a protein bound to histones in vitro it is probable that such an interaction may not occur in vivo as very little of the adenovirus protein co purified with chromatin from transformed cells. None of the Ad-12 E1 proteins showed any ATPase or protein kinase activity. PMID- 6239910 TI - Increased rate of suicide among patients with Huntington's disease. AB - The proportion of deaths attributed to suicide was examined among 506 deceased individuals with diagnosed or suspected Huntington's Disease from New England USA. Comparison of this proportion with that of the general population indicated that the odds of a death being due to suicide in the Huntington's disease group is 8.2 times that of the Massachusetts population for persons aged 50 to 69 yr, but no difference appears in the 10 to 49 yr age group. Among the 157 Huntington's disease patients for whom cause of death was known, the corresponding odds estimates are 23.0 for the 50 to 69 yr age group and 2.7 for the 10 to 49 yr age group. More than half of the suicides occurred in individuals who showed early signs of the illness but who had not been diagnosed, suggesting that suicide may occur more frequently in the early stages of the illness. PMID- 6239911 TI - Motor behaviour modifications after a stroke in a patient with Huntington's disease. PMID- 6239912 TI - Plasma membrane Ca2+ transport, and Ca2+ handling by intracellular stores: an integrated picture with emphasis on regulation. PMID- 6239913 TI - Angioplasty of supraaortic arteries. PMID- 6239914 TI - Early diagnosis of pulmonary osteoarthropathy in neoplastic disease. PMID- 6239916 TI - Dentist? Physician? Doctor? PMID- 6239915 TI - Static ergonomic strength testing in evaluating occupational back pain. AB - Quantitatively describing work limitation due to occupational back pain is difficult. Static ergonomic strength testing (SEST) was employed as part of a multidisciplinary evaluation program for occupational back pain, providing a quantitative description of lift ability in several positions. Comparison of intrasubject with intersubject variation confirmed that SEST did truly measure a personal characteristic. The expected degree of intrasubject variability is independent of the degree of impairment and provides a guide for detecting inadequate subject efforts. The technique allows worker-specific work restriction limitations to be recommended. PMID- 6239917 TI - Flow velocity patterns of the lower limb arteries investigated by a pulsed Doppler ultrasound flowmeter. A study in healthy control subjects. PMID- 6239918 TI - Measurement of pulsatile flows and variable volumes by bolus injection of indicator in a model of the pulmonary circulation. AB - The reliability and accuracy of the bolus injection-dye dilution technique were assessed for a physiological range of frequencies (13-49 min-1) and stroke volumes (60-160 ml) on a glass model where flows and volumes varied as a preset function of time (n = 320). We found that the technique overestimates flow by about 8% with a 95% confidence interval of +/- 10% for one measurement. Mean transit times are accurate within a +/- 7% confidence interval for one measurement. In a time-dependent flow and volume system this technique measures the mean volume as related to time with fluctuations up to +/- 30% around the mean. Results are independent of time and site of injection. The double injection single sampling technique gives results that are equivalent to those obtained by single injection and sampling of dye. PMID- 6239919 TI - Prediction of compliance with an over-the-counter acne medication. AB - As part of a larger study investigating treatment compliance with an over-the counter acne medication, 28 undergraduates were administered the Health Belief Questionnaire (HBQ), the Self-Consciousness Scale (SCS), and a Self-Efficacy Scale (SES). Stepwise regression analyses were performed with these scales as the predictors and the following measures as criterion variables: compliance rate, change in acne severity, change in number of acne lesions, dropout, and satisfaction. Results indicate that the HBQ significantly predicted outcome on a number of measures and was a better predictor than self-consciousness or self efficacy. PMID- 6239921 TI - Physiopathologic changes during anesthesia administration for gynecologic laparoscopy. AB - The physiopathologic effects of CO2 pneumoperitoneum on the respiratory and cardiovascular systems were studied in seven patients during gynecologic laparoscopy and volume-controlled ventilation. The CO2 pneumoperitoneum and Trendelenburg position induced a statistically significant decrease in CTL and a significant increase in CVP, PaCO2 and PACO2. PMID- 6239920 TI - Steroid metabolism in corpora lutea of the western spotted skunk (Spilogale putorius latifrons). AB - The present study reports steroid metabolism by corpora lutea (CL) obtained from skunks with diapausing embryos ('delay' CL) and with activated embryos (activated CL). CL from both reproductive periods were incubated with various radioactive precursors. Control incubations without any tissue or with 50 microliter of packed skunk blood cells were also conducted simultaneously. Incubation of skunk CL with [3H]-pregnenolone for 3 h resulted in 36% of the precursor accumulating as progesterone. Metabolism of [3H]dehydroepiandrosterone (DHEA) to androstenedione proceeded with approximately the same amount of product accumulating (34-46%) as was observed in the conversion of pregnenolone to progesterone. These results suggest that delta 5 isomerase, 3 beta-hydroxysteroid dehydrogenase, is the most prominent enzyme in skunk CL. Metabolism of [3H]pregnenolone to 17 alpha-hydroxypregnenolone and [3H]progesterone to 17 alpha hydroxyprogesterone occurred at low rates (1-7%), suggesting the presence of C21 steroid 17 alpha-hydroxylase in skunk CL. Aromatase activity, as estimated by measuring accumulation of oestradiol-17 beta from [3H]testosterone, was demonstrated in activated CL. These results suggest that skunk CL appear to metabolize steroids in a manner similar to CL of other mustelids such as the ferret and American badger. PMID- 6239922 TI - The pathogenesis of immune dysregulation in systemic lupus erythematosus. A troika. PMID- 6239923 TI - Location of tophi at Cushing's striae. PMID- 6239924 TI - Toxic pustuloderma--a new entity? PMID- 6239925 TI - Comparison of Fc gamma-receptors isolated from normal human serum and peripheral blood lymphocytes. AB - In this study, Fc gamma-receptors were isolated from normal human peripheral blood lymphocytes by prolonged incubation at 37 degrees C and purified by affinity chromatography using Sepharose 4B combined with heat-aggregated IgG. These labile Fc gamma R-receptors were shown to be functionally active with an apparent molecular weight of 60 K. Serum Fc gamma-receptor like molecules were also isolated and were shown to be of similar molecular weight. In addition, a high molecular weight (greater than 19S) serum IgG-binding protein was found. The basic sub-unit structure of this molecule was also 60K suggesting that the Fc gamma-receptor may exist in a polymeric or complexed form in normal human serum. PMID- 6239926 TI - Beta-2-microglobulin concentrations correlate with helper T cell counts in blood of homosexual men. PMID- 6239927 TI - Gratuitous induction. AB - We describe a novel mode of SOS induction, called gratuitous indirect induction, which is elicited when the maintenance of an intact lambda miniF introduced into a recipient was inhibited by a resident plasmid or by mutations in miniF that impaired partition or replication. Gratuitous induction required the presence of the lynA locus on miniF and was dependent on the host recA and lexA alleles. To account for gratuitous induction, we postulate that impairment of the normal co regulation between partition and replication of miniF affects lynA functions whose disturbance leads to the production of an SOS signal. PMID- 6239928 TI - Recombinational hotspot activity of Chi-like sequences. AB - Chi sites, consisting of the nucleotide octamer 5' G-C-T-G-G-T-G-G 3', stimulate coliphage lambda recombination mediated by the Escherichia coli RecBC recombination pathway. In a sensitive genetic assay using phage lambda crosses, three of four Chi-like sequences tested, namely 5' A-C-T-G-G-T-G-G 3', 5' G-T-T-G G-T-G-G 3' and 5' G-C-T-A-G-T-G-G 3', had about 6%, 11% and 38% of full Chi activity, respectively. We conclude that certain Chi-like sequences manifest a spectrum of recombinational hotspot activities and may account for RecBC-mediated generalized recombination of lambda lacking Chi sites. PMID- 6239929 TI - Subnormal expression of cell-mediated and humoral immune responses in progeny disposed toward a high incidence of tumors after in utero exposure to benzo[a]pyrene. AB - Pregnant mice were exposed to 150 micrograms benzo[a]pyrene (BaP) per gram of body weight during fetogenesis (d 11-17 of gestation) and the progeny were assayed for humoral and cell mediated immune responses at different time intervals after birth. Immature offspring (1-4 wk) were severely suppressed in their ability to produce antibody-(plaque-) forming cells (PFC) against sheep red blood cells (SRBC) and in the ability of their lymphocytes to undergo a mixed lymphocyte response (MLR). Lymphocytes from these progeny showed a moderate to weak capacity to inhabit production of colony-forming units (CFU) in host spleens following transfer with semiallogeneic bone marrow (BM) cells into lethally X irradiated recipients syngeneic to the BM (in vivo graft-versus-host response, GVHR). A severe and sustained suppression in the MLR and the PFC response occurred from the fifth month up to 18 mo. The in vivo GVHR, also subnormal later in life, was not as severely suppressed as the other two parameters. Tumor incidence in the BP-exposed progeny was 8- to 10-fold higher than in those encountering corn oil alone from 18 to 24 mo of age. These data show that in utero exposure to the chemical carcinogen BaP alters development of components needed for establishing competent humoral and cell-mediated functions of the immune apparatus and leads to severe and sustained postnatal suppression of the defense mechanism. The immunodeficiency exhibited, particularly in the T-cell compartment (MLR, GVHR), before and during the increase in tumor frequency, may provide a favorable environment for the growth of nascent neoplasms induced by BaP. PMID- 6239930 TI - Ultrasonic refraction by the rectus abdominis muscles: the double image artifact. AB - Using a real-time mechanical sector scanner in a transverse plane of section, the authors noticed that a double image of an intrauterine gestational sac or an intrauterine contraceptive device can be obtained when the transducer is passed over the midline of the abdomen. It was suggested that this is caused by refraction of the sound passing through the medial edges of both rectus abdominis muscles. The authors were able to reproduce this artifact in vitro using isolated human cadaver rectus muscles and imaging a single object in a water bath. PMID- 6239931 TI - The relationship between blood pressure and left ventricular muscle volume in normal children and adolescents--the Shimane Heart study. AB - Blood pressure (BP) and left ventricular muscle volume (LVMV) were measured in 408 children and adolescents aged 9-15 years. LVMV was determined by M-mode echocardiography. Lean body weight was approximately calculated using body weight, upper arm circumference and triceps skin fold thickness. Lean-BSA was obtained by substituting lean body weight for body weight in the formula for BSA. Subjects were divided into the high and the low BP percentile groups according to their BP percentile values. LVMVI (= LVMV/BSA) and lean-LVMVI (= LVMV/L-BSA) were compared between the two groups. LVMVI and L-LVMVI were larger in the high BP percentile group than in the low one. Regression lines of LVMV to BSA were also compared between the two groups. Regression lines of the high BP percentile group were located in a higher position than those of the low percentile group. These results suggest that LVMV are larger in the high BP percentile group than in the low percentile group even if their BSAs are equal. We concluded that left ventricular hypertrophy has been already initiated in the pre-hypertensive stage of human beings as observed in spontaneously hypertensive rats. PMID- 6239932 TI - Analysis of current source of the heart using isomagnetic and vector arrow maps. AB - Vector arrow maps and isomagnetic maps were constructed with a second derivative SQUID (superconducting quantum interference device) gradiometer in normal subjects and in various pathological conditions to study the inverse problem of electromotive forces and to determine whether the magnetocardiogram (MCG) provides different information from the electrocardiogram (ECG). The current sources deduced from these maps corresponded well with the activation sequences in normal and pathologic conditions reported previously. As second derivative gradiometer measures of the spatial differentiation of the magnetic field, these maps reflected well the current sources close to the anterior chest, namely the right ventricle and right atrium. In addition, it was possible to better localize the sources with this detector than with the ECG or first order gradiometer, suggesting that the isomagnetic and vector arrow maps obtained with the second derivative gradiometer were useful for solving the inverse problem. The MCG also provided different information from the ECG, so use of the MCG in addition to the ECG might be helpful in determining current sources more accurately. PMID- 6239933 TI - Analysis of structural proteins from biopsied human myocardium with special emphasis on methodology. AB - An analytical procedure for the quantitative determination of the structural proteins from a biopsied human cardiac muscle weighing approximately 1 mg was described to be applicable in clinical studies in 20 patients with various heart diseases. The principle of the method is glycerinization of heart muscle and analysis by SDS gel electrophoresis. In 6 control heart muscles obtained from patients having almost normal hearts, the pattern of the structural proteins was similar to that of the normal canine heart. Myosin heavy chain-actin ratio ranged 1.26 +/- 0.44. In 5 cases with secondary cardiac hypertrophy, the pattern of the structural proteins was the same as that of the control heart. In 4 cases with hypertrophic cardiomyopathy, an increase in myosin heavy chain was observed in 2 cases, while myosin heavy chain and alpha-actinin decreased in another 2 cases. Hypertrophy and severe disarray of myofibrils were noted in the former, and atrophy and degradation were done in the latter in electron microscopy. In 5 cases with dilated cardiomyopathies, the relative contents of myosin heavy chain and alpha-actinin was reduced in all cases together with atrophy and degradation of myofibrils. PMID- 6239934 TI - [Changes of hormone receptor status in various treatment for human breast cancer and DMBA tumor of the rat]. AB - Estrogen receptor (ER) and progesterone receptor (PgR) were measured by sucrose gradient centrifugation before and after various therapies, such as radiation, chemotherapy and hormone therapy. The subjects were 18 advanced or recurrent human breast cancers and 51 DMBA-induced mammary tumors of female SD rats. Changes of hormone receptors and the relationship between receptor levels and the effects of the therapies were examined. Changes of tumor cellularity were also studied in human breast cancers. Some ER-positive tumors changed into ER-negative and others did not. Most ER-negative tumors did not change in ER status. In the responsive cases, receptor levels tended to decline more remarkably and the cellularity of human breast cancer decreased. PMID- 6239935 TI - [A case of adrenocortical carcinoma with Cushing's syndrome presenting unusual urinary 17-ketosteroid fractionation]. AB - A patient with adrenocortical carcinoma with Cushing's syndrome is presented. This case seems to be most characterized by its very unusual urinary 17 ketosteroid (KS) fractionation, since markedly increased etiocholanolone was not accompanied by increments of either DHEA or androsterone. Determination of the plasma adrenocorticosteroids of the patient revealed normal DHEA and DHEA-S levels, moderately increased 17-OH-pregnenolone, and markedly increased 11 deoxycortisol. Therefore, it seems plausible that the unique 17-KS fractionation of this patient would have ensued as a result of remarkably decreased C17-20 lyase activity sufficient to nullify the increased 17-OH-pregnenolone and that markedly increased etiocholanolone might have been converted from 11 deoxycortisol. PMID- 6239936 TI - [Immuno- and enzyme histochemical study on mycosis fungoides]. PMID- 6239937 TI - [Spinal deformity and back pain in spinal osteoporosis]. PMID- 6239938 TI - Electrophoretic variants of blood proteins in Japanese. I. Phosphoglucomutase-2 (PGM2). PMID- 6239939 TI - [Sensor technology to control artificial organs]. PMID- 6239940 TI - [A study of glomerular C3b-receptor: the physicochemical characteristics and the changes in glomerulonephritis]. PMID- 6239941 TI - Scanning electron microscopic study on glomerular lesions in MRL/MpJ lpr mice. PMID- 6239942 TI - [Percutaneous transluminal coronary angioplasty (PTCA)]. PMID- 6239943 TI - [Questions and answers on rehabilitation. 9. Self-sufficiency of a child and the role of his parents]. PMID- 6239944 TI - Lysis of fresh human tumor cells by autologous large granular lymphocytes and T lymphocytes: two distinct killing activities induced by coculture with autologous tumor. AB - The specific and natural killer (NK)-restricted nature of autologous tumor killing by blood lymphocytes was studied in patients with carcinomatous pleural effusions. Large granular lymphocytes (LGL) and small T-lymphocytes were isolated by centrifugation on discontinuous Percoll density gradients. Tumor cells freshly isolated from pleural effusions of cancer patients were classified according to their susceptibility to purified LGL from normal donors in a 4-hour 51Cr release assay. Of 15 NK-sensitive tumors, 14 were lysed by fresh autologous LGL, whereas only 2 were killed by T-cells. Neither LGL nor T-cells were cytotoxic to NK resistant autologous tumor. LGL and T-cells were then cultured in vitro with autologous tumor cells for 6 days. In 13 of 15 autologous mixed lymphocyte-tumor cultures (MLTC) NK-sensitive tumor-cultured LGL maintained their autotumor killing activity, whereas LGL cultured alone lost the activity. Depletion of high affinity sheep erythrocyte-rosetting cells from Percoll-purified LGL resulted in an enrichment of effector cells. LGL from autologous MLTC were able to kill NK susceptible allogeneic effusion tumor and K562 as were fresh LGL. No lysis of NK resistant autologous tumor was observed with cultured LGL. In contrast, activation of T-cells in autologous MLTC resulted in the generation of autotumor killer cells in 10 of 15 NK-sensitive and 3 of 6 NK-resistant tumor samples. However, cultured T-cells were incapable of killing allogeneic tumor and K562. In autologous MLTC T-cells proliferated in response to autologous tumor, whereas no proliferation was observed in the culture of LGL. The enrichment of blasts from cultured T-cells on discontinuous Percoll gradients induced an augmentation of autotumor cytotoxicity, with no reactivity in blast-depleted, small, resting T lymphocytes. These results indicated that 2 distinct types of autotumor recognizing lymphocytes, LGL and T-cells, are present in the peripheral blood of cancer patients. PMID- 6239945 TI - A comparison of the effects of various anesthetic agents on selected criteria during postoperative recovery. PMID- 6239946 TI - [Renovascular hypertension 1984]. PMID- 6239947 TI - [Giant lipoma of the anterior mediastinum simulating heart disease]. PMID- 6239948 TI - [Morphological study of the myocardium of monkeys after anti-orthostatic hypokinesia]. AB - By histological, morphometric and gravimetric methods the hearts of 7 monkeys exposed to head-down tilt at -6 degrees were examined (2 monkeys were exposed to head-down tilt for 7 days and 5 monkeys were exposed to hypokinesia for 7 days and then to head-down tilt for 12 days; 4 additional monkeys were used as controls). During head-down tilt the heart weight increased due to blood pooling in the Thebesian vessels which was in turn associated with blood redistribution and accumulation in the vessels and parenchymal organs of the upper body. During 7- and 12-day head-down tilt myocardiocytes of the papillary muscles of the ventricles were not enlarged, and the number of functioning capillaries in the papillary muscles diminished. PMID- 6239949 TI - Sexuality education for the visually and hearing impaired child in the regular classroom. AB - With more than two million handicapped children being "mainstreamed" into the regular classroom, teachers are confronted for the first time with assisting visual- and hearing-impaired children. Sensory-impaired children usually will demonstrate a deficiency in psychosocial-sexual adjustment, and teachers may doubt their ability to help in this area. These children have the same emotional and social needs as others, and their maladjustment is due usually to a lack of sufficient information concerning their sexuality. With a better understanding and an early recognition of the impediments these individuals experience in acquiring sexuality information, teachers can modify their methods of presentation and provide opportunities and assistance in the child's psychosocial sexual adjustment. PMID- 6239950 TI - Utilization of general case programming for teaching health education behaviors to students with severe handicaps. AB - Students with severe handicaps are acquiring safety behaviors through the implementation of systematic instruction. Absent from this instruction is the inclusion of generalization strategies. Included in this article is a procedure for selecting representative teaching examples to promote optimal generalization. This procedure is referred to as general case programming. The steps of this strategy are delineated using an example of applying an adhesive bandage to a cut. PMID- 6239951 TI - School health education for the chronically impaired individual. AB - Educators often find themselves confronted with the need to address health related problems of chronically impaired students. Specific needs often are demonstrated by chronically impaired individuals. The roles and responsibilities of the classroom teacher with respect to meeting these needs are discussed. In addition, suggestions about how these concerns can be addressed through existing classroom health instruction are offered. Teachers can use the health curriculum to compliment the efforts of parents and health-care providers in informing, supplementing, and reinforcing disabled students' knowledge, attitudes, and skills. In this way, chronically impaired children can be assisted to meet present and future health needs in a manner conducive to optimal growth and development. PMID- 6239952 TI - The effects of intergroup cooperation and intergroup competition on ingroup and outgroup cross-handicap relationships. PMID- 6239953 TI - EKG of the month. Anteroseptal myocardial infarction. PMID- 6239954 TI - Steroid sulfatase and 17 beta-hydroxysteroid oxidoreductase activities in mouse tissues. AB - The metabolism of estrone sulfate and dehydroisoandrosterone sulfate to the free, unconjugated steroids, estrone and dehydroisoandrosterone, was demonstrated in more than thirty different tissues from male and female BALB/c mice. The activity of steroid sulfatase, when expressed per mg tissue, was greatest in both the pituitary gland and the adrenal glands. The pituitary gland, however, had the lowest capacity for hydrolysis of steroid sulfates while the liver had the greatest capacity. 17 beta-Hydroxysteroid oxidoreductase activity also was demonstrated in all mouse tissues by the formation of estradiol-17 beta when using estrone sulfate as the substrate. The highest apparent activity for 17 beta hydroxysteroid oxidoreductase was found in lung tissue, and the greatest capacity to form estradiol-17 beta from estrone sulfate was found in liver, lungs, kidneys and testes. This study demonstrates that the majority of mouse tissues have steroid sulfatase and 17 beta-hydroxysteroid oxidoreductase activities. PMID- 6239955 TI - Skeletal changes in childhood acute lymphoblastic leukemia: correlation with the presence of the cALL antigen. AB - We studied the occurrence of the radiolucent metaphyseal bands in pretreatment skeletal X-rays and the phenotype of leukemic cell in 66 children with non-T, non B ALL. A striking correlation was found between the expression of the CALLA on the leukemic cell and the occurrence of the early metaphyseal bands. We speculate that the bands might reflect an ongoing anti-leukemic reaction which may have been in progress before the disease became clinically manifest and which is associated with relatively favorable prognosis after even a modest chemotherapy. PMID- 6239956 TI - Cyclosporin A and the immune response to transplantation antigens. AB - Cyclosporin A (CsA) is a promising new immunosuppressive agent with considerable clinical potential. In addition to its ability to prolong allografts and possibly induce transplantation tolerance, this agent appears capable of selectively affecting different T lymphocyte subpopulations. Thus, Cyclosporin A may not only be a useful drug in clinical transplantation, but it may also become an important immunologic probe allowing the dissection of complex cellular interactions involved in the immune response. PMID- 6239957 TI - Limiting dilution analysis of IL-2 production: studies of age, genotype, and regulatory interactions. AB - We have previously described a limiting dilution method for estimating both the frequency of mouse T helper cells that can respond to alloantigens by producing Interleukin-2 (IL-2) and the amount of IL-2 produced by each responding cell (together with its progeny). At these very low cell concentrations, the amount of IL-2 produced per cell is remarkably higher (30-300 X) than the amounts generated under conventional, high density, culture conditions. We show here that cells cultured at intermediate densities "regulate" the amounts of IL-2 produced, so that the IL-2 concentration becomes independent of helper cell dose. The much higher level of IL-2 produced at very low concentrations therefore probably represents the loss, by dilution, of a regulatory cell that is less frequent than the IL-2 producing cells themselves. We show also how limiting dilution methods can be applied to KLH-responsive IL-2 secreting cells, and to questions about the effects of genotype and age on IL-2 production (Key words: Interleukin-2, helper T cells, aging, suppressor cells). PMID- 6239958 TI - The effect of sequential multiple grafting of syngeneic newborn thymus on the immune functions and life expectancy of aging mice. AB - Enhancement of the immune functions and extension of the mean life expectancy were successfully performed in aging mice by sequential multiple grafting of syngeneic newborn thymus. In the first experiment, 2-month-old female C57BL/6 mice were grafted with either syngeneic newborn thymus or newborn spleen every 2 months, 5 or 6 times. A significant enhancement of T cell dependent immune functions were observed in the group sequentially grafted with newborn thymus, in comparison to that grafted with multiple sequential newborn spleen or with a single newborn thymus and that without a graft. In the second experiment, the same sequential grafting protocol was performed in middle aged mice at monthly interval for 4-5 consecutive months and the immune functions and survival rate were compared between the experimental and control groups. The immune functions were only partially rejuvenated, but an extension of the mean remaining life expectancy was observed in the experimental group (312 +/- 38 days) as compared with control (214 +/- 42 days), although maximal life-span was the same in both groups (1100 days). PMID- 6239959 TI - Age changes in size and number of muscle fibers in human minor pectoral muscle. AB - Micromeasuring studies have been made on the senile changes of the surgically resected minor pectoral muscles in 200 Japanese females of various ages (26-80 years). The microscopic differentiation between type I (red) and type II (white) fibers were made by the histochemically demonstrated myosin-ATPase activity with frozen sections and also by the immunohistochemical demonstration of beta-enolase in the paraffin sections with indirect antibody method. The decrease with age in weight of the muscle was not markedly observed. Muscle fibers of type I were significantly decreased in number and increased in size after 60 years of age. However, size of muscle fibers of type II decreased gradually after 40 years of age. However, size of muscle fibers of type II decreased gradually after 40 years of age. Total volume of type I muscle fibers was not changed according to age, on the contrary, that of the type II fibers decreased significantly after 60 years of age. PMID- 6239960 TI - [Familial keratosis punctata palmaris et plantaris associated with multiple lipomas]. PMID- 6239961 TI - The low back pain syndrome. Diagnostic impact of high-resolution computed tomography. AB - This article focuses on low back pain which is directly related to the spinal axis and its supporting structures (spondylogenic back pain). This type of back pain is particularly prominent in our society, is frequently managed surgically, and has benefited from most advanced diagnostic imaging with computed tomography. PMID- 6239962 TI - Interventional radiology. AB - Interventional radiology is defined as a radiologic subspecialty and the services provided are tabulated in this article; those services relevant to internists are described in greater detail. This article is intended as a survey, and the authors encourage the reader to consult the references provided for a more in depth review. PMID- 6239963 TI - [Antagonistic properties of Propionibacterium strains isolated from acne lesions]. PMID- 6239964 TI - Evidence for diabetes-induced alterations in the sulfation of heparin sulfate intestinal epithelial cells. AB - 35S-heparan sulfate (HS) metabolism by intestinal epithelial cells isolated from streptozotocin-diabetic and control rats was studied. In diabetic cells, a greater amount of 35S-radioactivity was incorporated into HS, however specific radioactivity of this polysaccharide was decreased. Studies into the distribution of sulfate residues in HS after selective deamination of the glucosamine units within the glycosaminoglycan (GAG)-chain, demonstrated that O-sulfate groups are preferentially located in relatively small deamination products: tetrasaccharides and disaccharides. A lower amount of radioactivity related to N-sulfate groups was found in HS from diabetic cells compared to that of control cells demonstrating that, in diabetes, less glucosamine residues within HS chains are subjected to N-sulfation. An increase in the percentage of 35-sulfate and in the percentage amount of uronic acid in tetrasaccharides of HS of diabetic cells indicated that a greater number of tetrasaccharides were generated by deaminative degradation of this HS. Since a decrease in the specific activity of uronic acid in disaccharides as in tetrasaccharides from HS of diabetic cells was observed, it is clear that the degree of O-sulfation of this HS is reduced. It is suggested, that "in vivo" changes in HS metabolism in diabetic intestinal epithelial cells lie in a disturbance in the degree of N- and O-sulfation of disaccharide units within the HS macromolecule. PMID- 6239965 TI - "The highest attainable standard": common goals of MCH and MR/DD professionals. PMID- 6239966 TI - Integration of bacteriophages lambda and phi 80 in wild-type Escherichia coli at secondary attachment sites. I. Formation of secondary lysogens. AB - The family of lambdoid phages displays a varying specificity of integration into the host chromosome. The lambda phage DNA failed to get inserted at the secondary site(s) of the gal operon (frequency less than 2.6 X 10(-8) in the presence of the primary (normal) att site. By contrast, phi 80 and the lambda att80 hybrid (lambda X phi 80) became integrated into wild-type Escherichia coli at at least two secondary att sites of the btuB locus, and the latter near purE and purC as well (frequency 2 X 10(-3)-10(-4). The integration of phi 80 and lambda att80 into btuB occurred with about the same frequency as in cells in which the normal insertion site had been deleted (0.7-4.0 X 10(-6). An analysis of the secondary lysogens with the prophage in btuB showed them to be polylysogens; the additional prophage(s) was found at the primary att site. We also failed to observe the integration into other loci of phi 80 and lambda att80 with the formation of secondary monolysogens (frequency less than 0.0035 at MOI = 10(-3) or 10). It is presumed that these prophages become integrated at secondary att sites only if the primary site is occupied. PMID- 6239967 TI - Transduction of multi-copy plasmid pBR322 by bacteriophage Mu. AB - The temperate bacteriophage Mu transduces the 4363 bp multi-copy plasmid pBR322 at frequencies similar to those of chromosomal markers. Plasmid transducing particles contain DNA molecules of Mu DNA length. Plasmid DNA is transduced as a head-to-tail oligomer that becomes circularized in the recipient cell. The rec system of the donor strain participates in oligomer formation and the rec system of the recipient strain is required for oligomer circularization. Possible mechanisms that may explain the origin of plasmid transducing particles are discussed. PMID- 6239968 TI - Hemostasis: the balance concept of procoagulant and inhibitor systems and use of the serial thrombin time (STT). AB - The balance concept between the procoagulant and inhibitor systems allows a perspective to better diagnose opposite hemostatic mechanisms, especially hemorrhagic tendencies as a result of intravascular consumption coagulopathy from pathologic fibrinolysis. Concepts presented are intended to provide a base for following the ever changing patient therapeutic response in the course of these sometimes fulminant conditions. A concise description of the Serial Thrombin Time test (STT) is presented as a rapid quantitative test for the differentiation of opposing mechanisms affecting hemostasis. Typical patient cases are presented to demonstrate the use of the STT in diagnosis, selection of therapeutic agents, and management of hemorrhagic episodes. Presented are cases of disseminated intravascular coagulation, primary fibrinolysis, coronary thrombosis, and hemophilia. PMID- 6239969 TI - Mixed lymphocyte culture (MLC) test and living related donor kidney transplantation. PMID- 6239970 TI - [Small intestine function in strongyloidiasis in the residence of a temperate zone]. PMID- 6239971 TI - [Range of the flight dispersion of Anopheles pulcherrimus Theo B]. PMID- 6239972 TI - [Infection of Dermacentor niveus Neum., 1897 ticks with the rickettsial causative agents of human and animal diseases on the territory of a preserve in the Amu Darya flood plane]. PMID- 6239973 TI - [Ecology and the mite fauna of house dust]. PMID- 6239974 TI - Is Libman-Sacks endocarditis an immune complex disease? PMID- 6239975 TI - Another case of back pain. PMID- 6239976 TI - [Prevalence of periodontal pathology and the need for treatment in a group of handicapped adult subjects]. PMID- 6239977 TI - Genetic analysis of clear-plaque mutations induced in bacteriophage lambda by 9 aminoacridine. AB - Clear-plaque mutations were induced in the cI and cII genes of lambda by treating lysogenic cells with 9-aminoacridine (9AA). Mapping of the mutations revealed that there were two hot spots for 9AA mutagenesis in cI, and one strong hot spot in cII. The hot spots in cI mapped close to 1 of the 3 runs of 4 G/C base-pairs and near the only run of 5 G/Cs, respectively, in this gene. Of 36 cI mutations tested, at most one mapped near a run of 6 A/T base-pairs. By analogy, the sequence responsible for the strong hot spot in cII may be the run of 6 G/Cs in this gene. PMID- 6239978 TI - DNA-DNA and DNA-protein crosslinking and repair in Neurospora crassa following exposure to nitrogen mustard. AB - A new method was developed for the analysis of DNA-protein crosslinks in Neurospora crassa. The formations of DNA-protein and DNA-DNA crosslinks were assayed following exposure of spheroplasts to HN2. Both types of crosslink were detected and were found to be repaired during recovery. Moreover a mutant sensitive to HN2 was defective in the removal of both types of crosslink. PMID- 6239979 TI - Sister-chromatid exchanges and chromosomal aberrations in lymphocytes of male albino rats treated with an alkylating agent, apholate (NSC 26, 812; ENT 26, 316). AB - A lymphocyte culture system was used to study the frequency of chromosomal aberrations and SCEs at various time intervals after an intraperitoneal injection of apholate (0.5 mg/kg b.w.) in male albino rats. Treatment with apholate increased the frequency of chromosomal aberrations significantly (P less than 0.001). The majority of chromosomal aberrations were single chromatid breaks, although other aberrations were also present. The distribution of chromatid breaks was non-random and the large chromosomes were affected to a greater extent. SCEs frequency in lymphocytes of apholate-treated rats was more than 5 fold higher in comparison to controls. The highest number of chromosomal aberrations and SCEs/rat was recorded at 48 h post-treatment, after which there was a gradual decline in both SCE and chromosomal aberration frequency. The results indicate that apholate is a mutagenic compound and it may also be carcinogenic. PMID- 6239980 TI - [Transformation reactions of special metals in organisms and in the environment. 2. Abiotic methylation reactions of mercury, especially by methyltin compounds and humic and fulvic acids]. AB - Following a literature survey concerning abiological methylation reactions including transmethylation of mercury we present the results of transmethylation experiments. Model experiments in aqueous solution show an instantaneous methylation of mercuric chloride by mono-, di-, and trimethyltin chloride, the dimethyl compound having the highest rate of formation. The same is valid for similar experiments with soils, in which influences of the kind of soil also play a certain role. The methylation experiments of HgCl2 with humic and fulvic acids isolated from soil yielded positive results only in some few of the extracts and only with humic acid fractions. PMID- 6239981 TI - Dandruff and seborrheic dermatitis. PMID- 6239982 TI - [Laparoscopic findings in healthy women]. PMID- 6239983 TI - Circulating immune complexes (CIC) in connective tissue diseases (CTD). PMID- 6239984 TI - Assessment of reticuloendothelial system function in man using receptor-specific probes. PMID- 6239985 TI - Treatment of immune complex diseases. PMID- 6239986 TI - In situ formation of immune complexes in renal disease. PMID- 6239987 TI - Experimental allergic encephalomyelitis in mice: adoptive transfer of disease is modulated by the presence of natural suppressor cells. AB - Normal, untreated syngeneic recipients of lymphocytes from mice with experimental allergic encephalomyelitis (EAE) do not generally express adoptively transferred disease. Cell transfer of EAE is more successful when syngeneic recipients are treated with cyclophosphamide (CY) prior to the injection of donor cells. Normal, untreated recipients that do not develop EAE after receiving EAE donor lymphocytes are also unresponsive to subsequent encephalitogenic challenge. Those CY-treated recipients that fail to develop EAE after cell transfer do develop EAE after subsequent challenge. After reconstitution with normal splenic lymphocytes, CY-treated recipients do not develop EAE after subsequent challenge. These findings suggest the presence of an intrinsic natural suppressor cell subpopulation in naive mice which modulate the expression of adoptively transferred T lymphocytes. PMID- 6239988 TI - Brain tumors and plasmin inhibitors. AB - Four different intracranial neoplasms inhibited purified plasmin in an in vitro assay. The greatest inhibition (80%) was observed with extracts of a parasagittal meningioma that had invaded and completely occluded the sinus. Significant inhibition (greater than 40%) was also observed with extracts prepared from a glioma surgically removed from a patient who had suffered three thromboembolic episodes during the preceding several months. Lesser (less than 30%) inhibition was obtained with extracts from two other patients who had no evidence of thromboembolic complications. This report constitutes the first demonstration of plasmin inhibition activity in association with brain tumors. Further studies will be required to test the hypothesis that certain intracranial tumors may escape host antitumor fibrinolytic activity by producing plasmin inhibitors and that plasmin inhibitors may play a role in the thromboembolic complications frequently seen in patients with intracranial neoplasms. PMID- 6239989 TI - Effects of photoradiation therapy on normal rat brain. AB - Laser photoradiation of the brain via an optical fiber positioned 5 mm above a burr hole was performed after the injection of hematoporphyrin derivative (HpD) in 33 normal rats and 6 rats with an intracerebral glioma. Normal rats received HpD, 5 or 10 mg/kg of body weight, followed by laser exposure at various doses or were exposed to a fixed laser dose after the administration of HpD, 2.5 to 20 mg/kg. One control group received neither HpD nor laser energy, and another was exposed to laser energy only. The 6 rats bearing an intracranial 9L glioma were treated with HpD, 5 mg/kg, followed by laser exposure at various high doses. The temperature in the cortex or tumor was measured with a probe during laser exposure. The rats were killed 72 hours after photoradiation, and the extent of necrosis of cerebral tissue was measured microscopically. In the normal rats, the extent of brain damage correlated with increases in the dose of both the laser and the HpD. In all 6 glioma-bearing rats, the high laser doses produced some focal necrosis in the tumors but also damaged adjacent normal brain tissue. We conclude that damage to normal brain tissue may be a significant complication of high dose photoradiation therapy for intracranial tumors. PMID- 6239990 TI - Psychosocial criteria for patient selection: review of studies and concepts for understanding chronic back pain. AB - Eighteen studies on psychosocial aspects of back pain are reviewed. Among six studies trying to differentiate pain of organic and functional origin, only two studies claim to be able to make such a distinction. Psychological disturbance- studied with a variety of instruments--proved to be an important factor affecting the reporting and measurement of pain (eight studies). Low disturbance can predict good outcome in both organic and functional pain (six studies). Psychological disturbance, however, seems to be equally the consequence and the cause of pain, and pain relief reduces psychological disturbance. Thus, the dichotomy of organic vs. psychogenic pain must be dismissed, and a holistic, interactive systems model must be advocated. Factors causing acute back pain should be differentiated from those leading to chronicity. A model for understanding the evolution of chronicity and a checklist for possible factors promoting chronicity are presented. PMID- 6239991 TI - A controlled double-blind study comparing binedaline and imipramine in the treatment of endogenous depression. AB - 50 hospitalized endogenously depressed patients (age 20-60 years, HAM-D greater than or equal to 18) were treated daily with 3 X 50 mg imipramine or 3 X 100 mg binedaline. Clinical and laboratory assessments were done before and on days 1, 3, 5, 15 and 30 of treatment. Mean Hamilton and Zung scores were statistically significant lower on day 30 when compared with pretreatment scores. No psychiatric, clinical or statistical differences were noted between the two groups. The efficacy of the clinical global impression scale was slightly higher in the binedaline groups. Frequency of side effects (specially anticholinergic) was lower in the binedaline group. CONCLUSION: binedaline is equally effective as imipramine, but with less side effects. PMID- 6239992 TI - [3 programs of collective intervention]. PMID- 6239994 TI - Back pain: how health education affects patient compliance with treatment. PMID- 6239993 TI - Medicine Adverse Reactions Committee: eighteenth annual report, 1983. PMID- 6239995 TI - [Confidentiality and social psychiatric service]. PMID- 6239996 TI - [Social medicine evaluation of women employed while pregnancy]. PMID- 6239997 TI - [Violence against children--also a problem for physicians]. PMID- 6239998 TI - [Climatic cures at the ocean in childhood]. PMID- 6239999 TI - [Mental handicaps from the genetic viewpoint]. PMID- 6240000 TI - [Pediatric audiology, prevention and economics]. PMID- 6240001 TI - [Halogenated hydrocarbons--an environmental problem]. PMID- 6240002 TI - [Trends in suicide mortality in Austria]. PMID- 6240003 TI - [Serologic diagnosis and prevention of viral hepatitis]. PMID- 6240004 TI - [Passive smoking from the medical viewpoint--results of a discussion among experts]. PMID- 6240005 TI - Lens cortex irrigation/aspiration in extracapsular cataract extraction. AB - There are many good methods of removing lens cortex during extracapsular cataract extraction in use today. Features of some of these are presented. Flow volume of irrigation solution and depth of the anterior chamber are discussed, and it is recommended that adequate flow volume be used to maintain a comfortably deep anterior chamber during irrigation and aspiration. PMID- 6240006 TI - Studies on the involvement of melatonergic mechanism in intraocular pressure regulation. AB - It has been reported that diurnal changes in intraocular pressure (IOP) may be related to the fluctuation of melatonin levels in the eye. In order to test this hypothesis, effects of methysergide, tranylcypromine, and p-chlorophenylalanine (PCPA) on IOP recovery were studied in rabbits infused with hypertonic saline. Methysergide, a serotonin blocker at receptor sites, did not affect IOP recovery, presumably because it did not affect melatonin synthesis. Tranylcypromine, a monoamine oxidase inhibitor which preserves serotonin and eventually increases the level of melatonin in tissues, facilitated IOP recovery. PCPA, known to inhibit serotonin synthesis and to lower the melatonin level in tissues, markedly delayed IOP recovery. These results indicate that a chemical which decreases melatonin content in the eye also lowers the IOP and vice versa. It is suggested that some melatonergic mechanism is involved in the circadian rhythm of IOP. PMID- 6240007 TI - Vernal conjunctivitis in the hyperimmunoglobulinemia E syndrome. AB - Hyper-IgE syndrome (HIE) appears to be related to an immunoregulatory imbalance characterized by severe deficiency of suppressor T cells, elevated levels of IgE antibodies, and repeated infection of various organ systems. We report the association of HIE syndrome in two definite cases and one probable case of vernal conjunctivitis. This association suggests that T cell-mediated imbalance may be one factor in the pathogenesis of vernal conjunctivitis. PMID- 6240008 TI - Immunohistochemical and ultrastructural studies on the exenterated orbital tissues of a patient with Graves' disease. AB - The exenterated orbital contents obtained post mortem from a 47-year-old man who had an eight-month history of treated hyperthyroidism and a two-month history of visual complaints were examined histopathologically, immunohistochemically, and by electron microscopy. All of the extraocular muscles were massively enlarged, due to early diffuse endomysial fibrosis, mucopolysaccharide deposition, and a predominantly perivascular lymphocytic and plasmacytic infiltration. Histochemical stains revealed that the intramuscular mucopolysaccharides were weakly sulfated and polycarboxylated, establishing that they were products of fibroblastic activation rather than derived from mast cells. Subsarcolemmal deposits in the myofibers were shown by electron microscopy to be collections of glycogen rosettes with intermixed lipid deposits. These inclusions were interpreted as secondary phenomena due to abnormal muscle energetics from restrictions in contractility, and not as evidence of a primary degeneration of the extraocular muscle fibers themselves. The sarcomeric organization of the striated muscle cells was undisturbed, and therefore the pathologic changes occurred int he interstitial space of the endomysium. A monoclonal antibody specific for neurofilaments (antibody 4.3 F9) revealed, in comparison with normal controls, a preferential loss of large-type axons of the proximal segment of the orbital portion of the optic nerve as well as in the intracanalicular portion. The axonal loss was associated with a mildly increased number of astrocytes as demonstrated by an antibody against glial fibrillary acidic protein. The meninges of the optic nerve, the orbital fat, and the tendons of the extraocular muscles were uninflamed. The foregoing findings are compatible with a compressive optic neuropathy mediated by the massively swollen extraocular muscles impinging upon the optic nerve at the orbital apex. PMID- 6240009 TI - [Injuries in an agroindustrial region of intensive development and exploitation of irrigation systems in the steppes]. PMID- 6240010 TI - Rehabilitation of hearing-impaired adults. AB - Hearing loss produces a communication handicap which is not always predictable from audiometric results. Handicap questionnaires can be useful for identification of potential rehabilitation candidates. Hearing aids have been improved but cannot be expected to compensate for all the speech perception problems associated with sensorineural hearing loss. Other communication aids can be used to reduce hearing handicap. Effective use of devices often requires more instruction than is currently available. A comprehensive rehabilitation program takes into account individual circumstances and provides for a variety of services in addition to provision of aids. PMID- 6240011 TI - Liquid crystal thermography in the evaluation of chronic back pain: a comparative study. AB - This research involves the relative value of liquid crystal contact thermography (LCT) as compared to the physical examination, myelography, electromyography and CT scanning in the examination of 155 chronic low back pain patients. Thermograms were interpreted by two independent examiners as positive for nerve root compromise. Results demonstrate excellent interobserver reliability when used for this specific purpose and respectable correlations with the physical examination and EMG studies were obtained. Somewhat less correlation was found between LCT and the diagnostic procedures of CT scanning and myelography, especially in the postoperated patient. Liquid crystal contact thermography shows some promise as an adjunctive diagnostic tool in the assessment of chronic back pain patients with radicular symptoms, especially where further surgery is contemplated and the more structural tests of CT scanning and myelography may be falsely positive as a result of previous back surgery. PMID- 6240012 TI - Biochemical surface components of Brugia pahangi microfilariae. AB - The sheath and cuticle of microfilariae of Brugia pahangi were examined by electron microscopy and the presence of various proteins, carbohydrate and enzymes sought. The epicuticle of microfilariae consists of a pentalaminate structure (24.0 +/- 1.4 nm), a cortex (13.7 +/- 3.6 nm) and a basal zone (27.8 +/ 4.8 nm) which is often banded in appearance. The pentalaminate layers are not continuous at the base of the interannular grooves. The sheath and the epicuticle of B. pahangi stained positively with concanavalin A and saccharated iron oxide. The sheath of approximately 50% of microfilariae showed activity for acid phosphatase, 5' nucleotidase and peroxidase, but not for ATPases, alkaline phosphatase or esterase. No enzymes were detected in the epicuticle although the cortex and basal layers of the cuticle did show enzymic activity. Structures beneath the cuticle in the main body of the worms contained considerable enzymic activity. Microfilariae directly isolated from the blood of infected cats were found by immunochemical means to carry serum proteins on their sheaths but not on their cuticles. These studies extend the definition of the outer structures of microfilariae and confirm that they significantly differ in morphology and enzyme content from typical mammalian cell membranes. PMID- 6240013 TI - Isolation and antigen analysis of surface tegument membranes from schistosomula of Schistosoma mansoni. AB - The outer tegument membranes of Schistosoma mansoni schistosomula have been removed by mechanical disruption in a hypotonic salt solution and partially purified by differential and sucrose density gradient centrifugation. Fractionation was monitored by measuring increase in specific activity of bound [125I]wheat-germ agglutinin (WGA), alkaline phosphatase and calcium-stimulated ATPase. Two-dimensional IEF/SDS polyacrylamide gel electrophoresis was used to analyse the peptide composition of the isolated membranes and to compare and contrast with lactoperoxidase/glucose oxidase surface labelled peptides. At least 35 surface-labelled peptides were resolved on the two-dimensional maps: all were also present in the membrane material recovered from the sucrose gradient. Western blot analysis demonstrated a marked heterogeneity in the antibody response of infected human patients to individual membrane antigens. The antigenic profile of membranes isolated from cercariae, 18 and 96 h schistosomula were compared using Western blots: some minor differences were observed between the three preparations. PMID- 6240014 TI - [Lipid composition and ATPase activity of the myocardial sarcoplasmic reticulum in experimental hyperlipoproteinemia]. PMID- 6240015 TI - [Inv(9)(qh): a risk factor in Down's syndrome]. PMID- 6240016 TI - [Factors predisposing to chromosome pathology]. PMID- 6240017 TI - Characteristics and functional capacities of human cord blood granulocytes and monocytes. AB - Cord blood phagocytic cells were characterized with respect to cytochemical activities, Fc gamma and C3b receptors, and capacity to phagocytose and kill various species of bacteria. The percentages of peroxidase-positive granulocytes and monocytes from neonates and adults were comparable; the percentage of esterase-positive cord-blood monocytes was about two-thirds of that of adults' blood monocytes. The numbers of cord blood and adults' monocytes with Fc gamma and C3b receptors were similar. Phagocytic and intracellular killing capacities of cord blood granulocytes and monocytes were investigated for Staphylococcus aureus, Escherichia coli, Streptococcus pyogenes, and group B Streptococcus type III. The rates of phagocytosis and intracellular killing by granulocytes from newborns proved to be comparable to the corresponding values for granulocytes from adults. Cord blood monocytes phagocytosed E. coli, S. aureus, and S. pyogenes at a normal rate, and killed ingested E. coli and S. pyogenes intracellularly at the same rate as adults' monocytes did. However, S. aureus was killed at a much lower rate by cord blood monocytes than by monocytes from adults. Phagocytic activity for group B Streptococcus was impaired and killing of these bacteria by cord blood monocytes was virtually nil. The latter finding might partially explain the frequent streptococcal infections in newborns. PMID- 6240018 TI - Episodic secretion of hormones and the diagnostic value of single blood estimates. III. Testosterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulphate, cortisol. AB - The episodic fluctuation of serum testosterone, androstenedione, dehydroepiandrosterone (DHA), dehydroepiandrosterone sulphate (DHAS) and cortisol levels was analysed to determine the reliability of a single blood estimate in characterizing the mean value of a 4 h period. Radioimmunoassay of the steroids was performed in sera of 8 apparently healthy women in various phases of the menstrual cycle in 10 min intervals between 08 and 12 h a.m. Reliability criteria of the methods used were comparable to those in common use. The within-person fluctuation of individual values was determined by the coefficient of variation of single estimates, and the methodological error of the single estimates was characterized with the maximum increment from the mean at 95% confidential limits. A maximum deviation of 30.8, 28.6, 37.0, 25.0 and 61.2%, respectively, found in the above order of steroids, suggests several hormone estimations to be necessary for judging hormone availability in a subject. PMID- 6240019 TI - Societal activities and the handicapped: an informal look. PMID- 6240020 TI - Discrimination of computer-synthesized speech. AB - The effects of learning on the discrimination of computer-synthesized speech was assessed by presenting 100 computer-produced monosyllabic words to 2 groups of 15 adult subjects. One group's errors were corrected while the other group's errors were uncorrected. A comparison of errors on the first 50 vs the second 50 presentations showed significant improvement for corrected group only. It was concluded that the discrimination of computer-synthesized monosyllables can be improved with correction of errors but is still about 14% poorer than the discrimination of human speech. PMID- 6240021 TI - Myocardial necrosis in the newborn. PMID- 6240022 TI - [Chest roentgenogram in early stage after total correction of tetralogy of Fallot]. PMID- 6240023 TI - The oestrogenic Fusarium toxin (zearalenone) in hay as a cause of early abortions in the cow. AB - In this study, the occurrence of a series of early abortions in a herd of cattle kept at an experimental station in North Savo has been described, the cause of which has evidently been hay feed in which the toxin zearalenone had formed. Several early abortions occurred in this particular herd 30-90 days after artificial insemination had been performed. It was proved by means of a liquid chromatograph test that the hay contained 10 ppm zearalenone, and a biological experiment with rats gave a clear indication of its oestrogenic strength by means of the chloroform extract obtained with the hay. Early abortions ceased to occur after feeding with the suspected feed was discontinued. The cows were on heat again 2-23 days after the early abortions had occurred, though they subsequently experienced difficulties in becoming pregnant. PMID- 6240024 TI - Evaluation of five-year use of sealants. PMID- 6240025 TI - Organization and structure of the mouse interleukin-2 gene. AB - We have cloned a chromosomal DNA segment which covers the entire sequence for the murine interleukin-2 gene and analysed the structure of the gene. The coding regions are separated into four blocks by three introns each of which is located similarly to the corresponding human gene. The exon sequences can be aligned perfectly with the previously cloned cDNA sequence. Of particular interests is the presence of sequences within the 5'-flanking region which are highly conserved between mouse and man. The conserved region which spans more than 400 base pairs may play a role in the regulation of IL-2 gene expression. PMID- 6240026 TI - Balloon catheterisation. PMID- 6240027 TI - Learn from experience. PMID- 6240028 TI - [Non-hematologic adverse effects of cytostatic drugs]. PMID- 6240029 TI - Benefits of reducing--revisited. AB - The major premise by which weight reduction is used as a medical therapy is the fact that obesity is a primary risk factor in the onset and severity of many medical diseases. Hypertension, coronary artery disease, adult onset diabetes mellitus, complications of major abdominal and thoracic surgery, cancer of the breast and colon, and degenerative joint disease are prevalent diagnoses. The data to support weight reduction use as a medical therapy derive primarily from studies of cardiovascular disease. These studies show lowering of blood pressure and reduction of risk factors for glucose intolerance, angina, and hyperlipidaemia. The magnitude of weight loss (percent reduction in excess body weight) is important; 10 per cent reduction is a firm threshold in obese patients (greater than 130%- less than 200% ideal body weight). Success at achieving this medical therapy is most frequent using very low calorie diets which average 30 40% reduction of excess body weight. Mild and moderate hypertension will respond in 90% of patients. Type II diabetes mellitus patients can become free of exogenous insulin requirement. Response to general anaesthesia and control of respiratory distress syndrome will improve if preoperative weight loss is achieved. Improved cardiovascular fitness and relief of exertional dyspnoea are other clinically important outcomes of very low calorie diet therapy. A high priority exists to investigate the use of comprehensive professional weight control therapy as medical treatment. PMID- 6240030 TI - [High-amplification electrocardiography of cardiac micropotentials]. PMID- 6240031 TI - [Rush desensitization to respiratory allergens]. AB - Rush desensitization was introduced in 1930 and has been renewed by the advent of standardized, freeze-dried allergens of known and constant quality. It consists of giving rapidly progressive doses of allergens, followed by further injections of maintenance doses. In spite of relatively numerous adverse reactions--but not more than with the conventional method using the same aqueous preparations in the same doses--rush desensitization has proved very useful by providing rapid protection. Its effectiveness against allergy to pollens has been demonstrated by a controlled clinical trial and by responses to challenge tests performed before and after treatment. A decrease in skin reactivity has been noted soon after the maintenance dose is reached. Rush desensitization is accompanied by very slight changes in specific IgE levels and by a moderate but statistically significant increase in specific IgG levels. This method constitutes a suitable alternative to conventional immunotherapy in a substantial number of cases and probably involves different immunoprotective mechanisms. PMID- 6240032 TI - [Ovarian insufficiency in congenital galactosemia]. AB - Primary ovarian failure was observed in 2 sisters aged 17 and 4 years respectively presenting with congenital galactosaemia. The diagnosis of ovarian failure, clinically suggested in the older girl by the absence of puberty, was confirmed in both cases by a massive increase of baseline and post-stimulation plasma gonadotrophins. The elder sister had extremely low plasma oestradiol levels, and her ovaries were reduced to two strips of fibrous stroma almost devoid of follicles. In both cases the other endocrine glands seemed to be normal. Since the younger girl had received a galactose-free diet from birth, exogenous galactose toxicity could be ruled out. It appears from an analysis of the other 5 published reports that a metabolite of endogenous galactose is responsible for the ovarian lesions. The toxic effects of this metabolite may begin during intra-uterine life or after-birth. PMID- 6240033 TI - [Hepatic metastases. Value of chemotherapy by the intra-arterial route]. AB - Forty-three patients with metastatic liver cancer were treated with multiple chemotherapy by the intra-arterial route. Metastases originated from primary cancer of the breast (16) or colon (10), melanoma (7) and miscellaneous tumours (10). In 35 patients chemotherapy was administered by selective catheterization of the hepatic artery via the axillary artery; it usually (31 cases) consisted of doxorubicin (60 mg/m2) and mitomycin (10 mg/m2) injections, and continuous infusion of 5-fluorouracil (1 g/24 or 72 hours). In 14 patients (10 responders to the above method and 4 new cases), a catheter with subcutaneous chamber was implanted surgically so that chemotherapy could be continued through the chamber. Blood toxicity was usually moderate. The main complication of injections through the catheter (114) or through the chamber (60) was thrombosis. However, except for 1 lethal cerebral thrombosis, the others (axillary artery 3, hepatic artery 5) were unattended by functional symptoms. Transient biochemical signs of hepatic cytolysis were frequent after each course. Hepatic insufficiency was severely aggravated in 2 cases. Painful digestive disorders were relieved by symptomatic treatments. Four complete responses, 16 partial responses, 8 stabilizations and 10 failures were observed; 5 patients died soon after one single course of intra arterial therapy. The high response rates (greater than 50%) in metastases from cancer of the breast and colon, and chiefly the 3 complete responses obtained in patients with mammary carcinoma were most encouraging, bearing in mind that one of these 3 patients had not responded to intravenous chemotherapy. PMID- 6240034 TI - [Diffusion of fosfomycin into the cerebrospinal fluid in purulent meningitis]. AB - Cerebrospinal fluid levels of fosfomycin were measured in 10 patients with bacterial meningitis. Fosfomycin 200 mg/kg/day was administered in three 4-hour intravenous infusions. The antibiotic was associated with amoxicillin in 9 patients and with cefotaxime in one. Cerebrospinal fluid was obtained on the 2nd and 5th days of treatment, 2 hours after the end of the infusion. The mean CSF fosfomycin levels were 31 mg/l on the 2nd day and 37.2 mg/l on the 5th day. These levels were higher than the MIC 90 for most bacteria encountered in meningitis. Fosfomycin could be used to treat some cases of bacterial meningitis, but always in association with another antibiotic. PMID- 6240035 TI - [Mechanisms of allograft rejection]. AB - Recent studies have considerably altered our understanding of allograft rejection mechanisms. The new approaches concern rejection targets, effector mechanisms, the triggering of the immune response and the genetic control of the immune response. Rejection targets now regarded as most important are antigenic epitopes such as "tissue specific" antigens, vascular endothelium antigen, skin Epa antigen and the minor histocompatibility antigen H-Y. Effector mechanisms seem to be restricted almost to the lymphocyte Th helper subset rather than to the Tc cytotoxic subset. The triggering of the immune response is mainly effected by certain cells, e.g. dendritic cells and Langerhans cells, or by lymphokines, such as interleukin 2. Finally, the genetic control of the response to alloantigens, previously demonstrated for less complex systems, is now known to exist in allograft rejection. PMID- 6240036 TI - [Use of intraluminal dilatation catheters in the surgical treatment of pulmonary atresia with intact septum]. AB - Despite considerable progress in surgery and intensive care and the advent of prostaglandins, pulmonary atresia with intact ventricular septum remains a severe heart disease. The authors describe a technique of pulmonary valve plasty across the right ventricule, using dilatation balloon catheters for peripheral arteries. This technique proved successful after a 4 to 12 months follow-up in 2 out of 4 neonates who underwent surgery. It is fast, causes little damage to the right ventricle and could be improved by using catheters specifically designed for this type of surgery. PMID- 6240037 TI - [Drug-induced oxalic lithiasis from pyridoxilate]. PMID- 6240038 TI - [Demyelinating encephalopathy during the development of breast cancer. Value of nuclear magnetic resonance]. PMID- 6240039 TI - [The string test in the diagnosis of typhoid fever]. PMID- 6240040 TI - [Hyperglycorrhachia in acute monoblastic leukemia with meningeal localization]. PMID- 6240041 TI - [Realistic nasal provocation tests]. PMID- 6240042 TI - [Role of endorectal echography in the diagnosis and surveillance of anorectal tumors]. PMID- 6240043 TI - [Voluntary poisoning with captopril]. PMID- 6240044 TI - [An infection with Chlamydia trachomatis can conceal another infection]. PMID- 6240045 TI - [Retrospective evaluation of an algorithm for the etiological diagnosis of hypercalcemia]. AB - Aetiological diagnoses obtained by means of an algorithm were retrospectively compared with those made in the Internal Medicine Department of the La Pitie Hospital, Paris, in 22 cases of hypercalcaemia (24 causes detected). These cases covered all the usual causes of the disease. The algorithm produced no erroneous diagnosis. In 2 cases it would not have resulted in a precise diagnosis, but in all other patients the diagnosis obtained by this method was in agreement with the clinical diagnosis. Proposals are put forward for an improved version of the algorithm that would provide more rapid diagnoses and avoid the risk of a "no diagnosis" answer. PMID- 6240046 TI - [Prevalence of antinuclear antibodies in hypertensive diabetics treated with acebutolol]. AB - Acebutolol may induce the development of antinuclear antibodies and, exceptionally, of a lupus-like syndrome. The purpose of this study was to evaluate the prevalence of antinuclear antibodies in hypertensive diabetics under long-term treatment with acebutolol. Seventy-eight normal subjects, 75 diabetics under antidiabetic therapy only, and 75 hypertensive diabetics who received acebutolol in mean doses of 478 +/- 242 mg/day for at least one year were investigated. The 3 groups were comparable with regard to age and sex. Antinuclear antibodies were detected in 18.6% of diabetics under acebutolol, as against 3.8% and 1.3% respectively of subjects in the other groups (p less than 0.01). There was no correlation between the levels of antinuclear antibodies and the dosage or duration of acebutolol treatment. None of the sera tested contained antinative DNA antibodies, and none of the hypertensive diabetics exhibited signs of lupus-like syndrome. PMID- 6240047 TI - [Incidence of antinuclear antibodies during treatment with acebutolol. A 1-year prospective study in 45 hypertensive patients treated by monotherapy]. AB - Determinations of antinuclear antibodies (ANA) were performed before treatment, then every 3 months for one year, in 45 hypertensive patients treated with acebutolol alone in daily doses equal or superior to 800 mg. Non significant ANA titers (1/10 to 1/40) were detected before treatment in 8.8% of the patients. After one year of treatment, 15.5% of the patients were found to have antinuclear antibodies. In 4 (8.8%) female patients (3 of whom were ANA-negative before treatment) the ANA titers were above 1/40. Treatment was discontinued in one of these due to the occurrence of bronchospasm. No lupus-like syndrome was observed during the course of the study. Prolonged prospective studies with acebutolol alone would be required to determine whether in the long term the incidence of significant ANA titers remains at the 8.8% level or increases. PMID- 6240048 TI - [Autoimmunity induced by drugs. Immunological characteristics and etiopathogenic hypotheses]. AB - Drug-induced autoimmune diseases have two immunological peculiarities. Firstly, some autoantibodies are present, which are virtually never seen in spontaneous human diseases and may be regarded as specific. This applies to antimitochondria antibody type 3 (anti M3) in the lupus-like syndrome caused by Venocuran, to antimitochondria antibody type 6 (anti M6) in iproniazide-induced hepatitis, to anti-insulin antibody found after treatment with methimazole, and to anti liver/kidney microsome antibody type 2 (anti LKM2) associated with hepatitis induced by tielinic acid. Secondly, a search for other autoantibodies shows that the immune disorder is much more limited than in spontaneous autoimmune diseases. Thus, contrary to myasthenia and idiopathic autoimmune haemolytic anaemia, we never found autoantibodies specifically directed against the thyroid, the stomach or the adrenal gland during treatment with D-penicillamine and alpha-methyldopa. Only some hypotheses may account for these peculiarities. Cross-reaction between drug and autoantigen may occur, but the fact that the antigen-antibody reaction is not inhibited by the drug or its metabolites does not support this explanation. Much more attractive is the "T-cell bypass" theory, according to which autoreacting suppressor T-cells are circumvented by helper T-cells stimulated by the drug-modified autoantigen. In this case, the autoimmune reaction would indicate to which body substance the drug is bound, thus making it immunostimulant, and not a structural similarity between the drug and the autoantigen. PMID- 6240049 TI - [Continuous positive pressure in the treatment of sleep apnea syndromes]. AB - Continuous positive airway pressure as a long-term home treatment for sleep apnea syndromes would seem to present irreconcilable requirements; it must be simple and comfortable to use during sleep and it must be relatively inexpensive. The device described in this paper includes a compressor, an individually molded nose mask and a water column. Improvements are still in progress, but, as it stands, it enables sleep apnea patients to be successfully treated at home. PMID- 6240050 TI - [Cancer of the kidney with cardiac metastasis. Value of bidimensional echography]. PMID- 6240051 TI - [Absolute and relative increase in Leu-11b+ cells in patients with systemic scleroderma]. PMID- 6240052 TI - [Value of the assay of carbohydrate antigen in the study of digestive cancers]. PMID- 6240053 TI - [Cardiac arrest. One cause can conceal another]. PMID- 6240054 TI - [Emergency destruction of the bundle of His by endocavitary electric shock. Apropos of a case of refractory supraventricular tachycardia in a respiratory insufficiency patient]. PMID- 6240055 TI - [Peptichemio treatment of a patient with terminal stage myeloma]. PMID- 6240056 TI - [Paraplegia due to aortic rupture]. PMID- 6240057 TI - [Efficacy of dexamethasone in the treatment of hyperthyroidism caused by amiodarone]. PMID- 6240058 TI - [Monoclonal gammopathy in systemic lupus erythematosus]. PMID- 6240059 TI - [Spontaneous hematoma of the brain stem disclosing hemophilia]. PMID- 6240060 TI - [Experience in organizing the sanatorium treatment of patients with ocular tuberculosis]. PMID- 6240061 TI - [Comparative analysis of the relationship between tuberculosis mortality and the type of tuberculosis facility]. PMID- 6240062 TI - Evidence for linkage between the loci coding for the binding protein for the fourth component of human complement (C4BP) and for the C3b/C4b receptor. AB - Three pedigrees informative for the segregation of genetic variants of the binding protein for the fourth component of complement (C4BP) and C3b/C4b receptor (C3bR) have been identified. There were 10 informative meioses with no recombinants, indicating a close linkage between the loci encoding C4BP and C3bR, C4BP and C3bR [maximum lod (logarithm of odds of linkage) score: 2.4 at recombinant fraction = 0.0]. In addition, in the four unrelated individuals who were doubly heterozygous (C4BP*1, C4BP*2, C3bR*A, C3bR*B), the infrequent allele C4BP*2 segregated together with the uncommon allele C3bR*B, supporting the hypothesis of linkage between C4BP and C3bR and suggesting that linkage disequilibrium exists between these particular alleles. We conclude that the loci encoding C3bR and C4BP, two functionally related molecules, are linked. PMID- 6240063 TI - Molecular, mechanistic, and functional aspects of the plasma membrane calcium pump. PMID- 6240064 TI - Modulation of hypercalcemia by dichloromethane diphosphonate and by calcitonin in a model of chronic primary hyperparathyroidism in rats. PMID- 6240065 TI - Aspects of laser light scattering from skin tissue with application to laser Doppler blood flow measurement. AB - Studies of both intensity and Doppler shifted linewidths of light scattered from skin tissue have been made using photon correlation spectroscopy and optical fibre techniques. Measurements as a function of the separation of input and detecting fibre positions show characteristic features. These features are interpreted in terms of the positions of the scattering red blood cells and the tissue structure. Evidence is given for an interpretation of the differences in the scattered light for scattering from superficial vessels including capillary loops and from deeper lying larger vessels and shunts. Measurements using various laser wavelengths are discussed. The results of this study are important in the development of laser light scattering instruments for the measurement of peripheral blood flow and microcirculation. PMID- 6240066 TI - Action spectra for hematoporphyrin derivative and Photofrin II with respect to sensitization of human cells in vitro to photoinactivation. PMID- 6240067 TI - [Serum testosterone determination in the antiandrogen therapy of sexual deviations with cyproterone acetate (preliminary report of experiences)]. AB - Total testosterone concentrations in the serum of patients treated with antiandrogens were measured by means of an industrially produced radioimmunological testosterone assay kit (VEB Sachsisches Serumwerk Dresden). Antiandrogen therapy using cyproterone acetate (Androcur) leads to a reduction in serum testosterone concentration which is significant at the p less than 0.01 level. The data suggest that testosterone concentrations vary inversely with increasing Androcur dosage; they are around 7 nmol/l at the doses conventionally administered. The testosterone concentrations obtained under depot-Androcur treatment suggest that intervals between injections should be less than 10 days. PMID- 6240068 TI - Effects of antiandrogen treatment on the sexuality of women with hyperandrogenism. AB - Although one can reasonably infer that antiandrogens are likely to have a marked negative impact on female sexual responsiveness, the side effects of cyproterone acetate (CPA) treatment in hirsute women have been neglected in previous studies. The purpose of this study was to investigate the psychosexual situation of 61 hirsute women before and under hormonal treatment. 21% of the hirsute women were diagnosed as having been sexually dysfunctional before starting hormonal treatment. 44% of the women under antiandrogen treatment reported that their sexual enjoyment was impaired due to the hormonal treatment. Taking into account only those women living in a stable partnership, the percentage goes up to 61%. The conclusion from these results is to give a more detailed account of the possible side effects to the women involved in CPA treatment. PMID- 6240069 TI - Autosomal dominant polycystic kidney disease: symptoms and clinical findings. AB - In 259 subjects at risk to have inherited autosomal dominant polycystic kidney disease (PKD), the frequency of symptoms consistent with urinary tract infection, haematuria, back and abdominal pain, hypertension, renal stones, and end-stage renal failure was evaluated. The diagnosis of PKD was made in 140 of these subjects (54 per cent). At the time of the study, 36 per cent of males and 7 per cent of females with PKD were asymptomatic, normotensive, and denied any previous problems. In patients younger than 30 years, 66 per cent of males but only 11 per cent of females were asymptomatic. In female patients, urinary tract infection (69 per cent) and hypertension (61 per cent) were the most frequent clinical manifestations. In contrast, in males with PKD, these problems were present in only 19 per cent and 42 per cent, respectively. Frequency of other clinical manifestations was similar in women and men with PKD. End-stage renal failure was present in 5 per cent of the 81 patients younger than age of 40, in 33 per cent of the 27 patients 40-49 years old, and in 47 per cent of the 32 patients aged 50 years or more. Physical examination was unreliable in estimating kidney size in most patients, particularly in early stages of the disease. Hypertension and symptoms such as haematuria and back pain, but not urinary tract infections, correlated well with renal size measured by radiograms. PMID- 6240070 TI - Effect of placement technique on the density of composite restoration in vitro. PMID- 6240071 TI - [Effect of a tortoise spleen extract on the functional state of liver mitochondria in irradiated mice]. AB - A study was made of the effect of a drug prepared from a spleen extract of Testudo horsfieldi on energy metabolism and lipid composition of liver mitochondria of irradiated mice (2.06 X 10(-1) C/kg). It was shown that the decompensated low-energy state of liver mitochondria of the exposed mice was changed into the state of the compensated low-energy shift: the physicochemical properties of lipid microenvironment of mitochondria proteins were partially restored. PMID- 6240072 TI - [Biosynthesis and biodegradation of GM2 ganglioside]. PMID- 6240073 TI - [beta-N-acethylhexosaminidase from Streptococcus pneumoniae]. PMID- 6240074 TI - [Skin changes in persons exposed to asbestos]. PMID- 6240075 TI - [Case of an occupational disease incorrectly diagnosed]. PMID- 6240076 TI - [Biology of T-cells studied using monoclonal antibodies. I. Subpopulations of T cell and monoclonal antibodies]. PMID- 6240077 TI - Changing views of the hazards of recombinant DNA manipulation and the regulation of these procedures. PMID- 6240078 TI - [Leakage of gaseous 125I from a Na125I solution through a plastic film]. AB - Leakage of gaseous 125I from the various kinds of plastic film bags packing Na125I solution was determined. The polyethylene bag was permeable to the gaseous 125I and active charcoal could not prevent the leakage. The laminated plastic bags composed of polyethylene terephthalate and polyethylene was slightly permeable, and the leakage decreased either in the presence of active charcoal or with the use of doubly packed bags. Leakage of 125I from the various kinds of container for the Na125I solution was also determined. PMID- 6240079 TI - [New clinical data on an old disease: renal abscess]. PMID- 6240080 TI - [Postoperative ulcer]. PMID- 6240081 TI - [Intestinal angiodysplasia]. PMID- 6240082 TI - [Hemorrhagic gastric cancer (clinical aspects and its treatment]. PMID- 6240083 TI - [Different indications for surgical treatment in relation to the clinical form of gonarthrosis]. PMID- 6240084 TI - [Microsurgery on the peripheral nerves]. PMID- 6240085 TI - [Side-to-side choledochoduodenal anastomoses in benign lesions of the biliary tract]. PMID- 6240086 TI - [Surgical treatment of sliding hiatal hernias (a technical variant)]. PMID- 6240087 TI - [An unusual etiological factor in traumatic rupture of the rectus abdominis]. PMID- 6240088 TI - [Perforating wound of the left ventricle undergoing emergency treatment]. PMID- 6240089 TI - [Recent injuries of the lower cervical spine]. PMID- 6240090 TI - [Lumbar stenosis with scoliosis. Symptomatologic study and surgical treatment of 39 cases]. AB - In 39 cases of narrowed lumbar spinal canal associated with a scoliosis, the authors have studied the role played by deviation of the spine and the origin of the narrowing. It seemed that central stenosis with intermittent claudication was more frequent when a scoliosis was present. In more than half of the cases, the level of the compression was at the junction of the curves. After failure of conservative treatment, the surgical procedure performed was the same as in straight spines. The results were satisfactory in 90 p. 100 as regards root involvement and intermittent claudication. However 7 patients had increased low back pain after surgery, 3 of them being disabled. In young patients with curves of more than 30 degrees with noticeable rotation, straightening with arthrodesis appeared to be worthwhile rather than simple posterior laminectomy. In other cases a posterior liberation of the cord associated with limited posterolateral fusion is indicated. PMID- 6240092 TI - [Laparoscopic aspects of neuroblastoma localized in the liver]. PMID- 6240091 TI - [Therapeutic indications in scoliosis of Duchenne muscular dystrophy. Apropos of 10 cases]. AB - Ten patients suffering from Duchenne muscular dystrophy were followed up for more than 7 years. The diagnosis was determined by biopsy. Progress of the disease was severe and all patients died before the age of 18. The average angle of the scoliosis at the end of this development was 73 degrees. The maximum vital capacity was 1198 ml. The authors conclude that neither the use of a brace nor adaptation of a wheelchair are helpful. Surgical treatment is hazardous when the curve is greater than 23 degrees. The indications for such treatment are based on the importance of the degree of pulmonary restriction and on early signs of severe progress of the scoliosis. PMID- 6240093 TI - [Functional muscular abdominal distension]. PMID- 6240094 TI - [Rehabilitation of the handicapped caught between content programming and economic justification]. AB - Notwithstanding the wide socio-cultural scope of theoretical social policy, those, at any rate, who are involved in practical social policy making time and again face the task of providing an economic justification for their respective programmes; the field of rehabilitation of the disabled is no exception to this rule. An economic justification of rehabilitation service provision would however imply their flexibility within economic development: content programming continuity and economic justification will clash as the economic situation changes. Maintaining, or honouring, present rehabilitation service programming will jeopardize economic justification, whereas orientation of rehabilitation practice toward economic justifiability would imply the need to abandon redemption of present content programming. This entails a normative dilemma between rehabilitation content programming, or goal-setting, on the one hand, and its economic-functional, theoretical justification as reflecting given economic circumstances on the other. This normative dilemma gives rise to critically re consider current practice in, and the rank accorded to, economic justification in rehabilitation service provision. PMID- 6240095 TI - [Bildschirmtext-Btx (the interactive videotex information system of the West German Postal Service): a medium for rehabilitation? Decision-making aids for the user]. AB - The rapid development of new electronic information technologies is outlined, which are definitely going to affect existing social and economic structures. The new medium Bildschirmtext Btx (the interactive videotex information system of Deutsche Bundespost) will, in the opinion of the author, radically change many aspects of our life, as had been the case with telephone and television. The question is therefore raised as to the part Btx might have in the field of communication among those involved in rehabilitation. The contribution explains what Btx is and how it works. Examples are given to illustrate the wide scope of possible applications, which make Btx a useful tool in rehabilitation as well. Besides, the question as to the cost involved is answered. In the opinion of the author this new Btx communication technology holds great potential to become the "medium in rehabilitation". PMID- 6240096 TI - On the mechanisms of the inhibition of calcium sequestering activity of liver microsomes in bromotrichloromethane intoxication. AB - The mechanisms by which the in vivo intoxication with BrCCl3 inhibits the calcium sequestration activity of liver microsomes were studied. The initial rate of Ca2+ transport is inhibited by nearly 50% in the intoxicated rats as compared to the controls; this indicates that the active transport of Ca2+ is markedly affected by the intoxication. The microsomal ATPase activities both in the presence and in the absence of Ca2+ were not decreased at all in the intoxicated animals. However, the Ca2+-dependent extra ATP-hydrolysis shows a different kinetics in the BrCCl3-poisoned rats with respect to the controls. The release of Ca2+ from Ca2+-loaded liver microsomes is higher in the intoxicated animals. It seems therefore that the increased permeability of the membrane to Ca2+ contributes to some extent to the haloalkane-induced inhibition of the calcium sequestration activity of liver microsomes. PMID- 6240097 TI - [Left ventricular function prior to and after transluminal coronary angioplasty (TCA)]. PMID- 6240098 TI - [Unsuccessful percutaneous transluminal coronary recanalization in coronary embolism]. PMID- 6240099 TI - Absence of left ventricular hypertrophy in thyrotoxic patients without congestive heart failure. An echocardiographic study. PMID- 6240100 TI - [Children at risk, handicapped children: early and pragmatic assistance]. PMID- 6240101 TI - [Percutaneous transluminal angioplasty in a patient with coronary arteriosclerosis]. PMID- 6240102 TI - [The cost of lumbago. A study at Fribourg in 1983]. PMID- 6240103 TI - [Surgical treatment of acne]. PMID- 6240104 TI - [ECG Quiz No. 26. What is your diagnosis?]. PMID- 6240105 TI - [Morphologic and functional transformation of muscle fibers induced by training]. PMID- 6240106 TI - [Diagnosis of peripheral arterial insufficiency in the amateur athlete with claudication and the detection of "the isolated iliac artery stenosis syndrome in young bicyclists with no risk factors" with the Doppler and rolling carpet tests]. PMID- 6240107 TI - [The family physician and the sick driver]. PMID- 6240108 TI - [Behavior of T lymphocytes, T helper and T suppressor, in multiple sclerosis. Preliminary report]. PMID- 6240109 TI - Fine-Needle aspiration biopsy of bone lesions in the spine: diagnostic value. AB - Fine-needle aspiration biopsy was performed in 92 patients with back pain and a lesion confirmed via x-ray of the spine. In 31 patients in whom x-ray findings had suggested spondylitis, fine-needle aspiration biopsy showed the presence of a tumour in three patients. Of 61 patients with radiographic findings suggestive of malignancy, 26 had benign unspecific lesions, and 35 patients had neoplastic lesions. There were four false negative cytological reports and one false positive report. Additional ESR determination was of no clinical value. There were no complications. Fine-needle aspiration biopsy of bone lesions is recommended as an easy, safe and very often a valuable diagnostic complement. PMID- 6240110 TI - [Comparative study of the action of fenoterol and of the fenoterol- ipratropium association on static pulmonary volumes and PaO2]. PMID- 6240111 TI - M-mode echocardiography in hypertensive heart disease. AB - Left ventricular hypertrophy (LVH) is both a target organ response to hypertensive vascular disease and a factor that might be responsible for other cardiovascular events. Therefore we studied by means of echocardiography 41 patients with untreated hypertension classified into 4 groups according to electrocardiographic and chest X-ray LVH criteria. The patients in group IV had in addition a history of coronary disease. Thirty-seven patients (92%) presented concentric LVH and 4 patients combined LVH and dilatation. Five patients from group IV presented impairment of interventricular septum or posterior wall motion. Thirty-seven patients (92%) had increased left ventricular mass (p less than 0.01). Ejection fraction was normal in groups I, II and III but significantly decreased (p less than 0.001) in group IV. We conclude that LVH is part of the natural evolution of hypertensive vascular disease. Echocardiography proved to be the most indicated method for the assessment of cardiac dimensions and function in hypertensive heart disease. PMID- 6240112 TI - Terminology, definitions and diagnostic criteria in digestive endoscopy. With the collaboration of the members of the Terminology Committee of the World Society of Digestive Endoscopy/OMED. PMID- 6240113 TI - Demonstration of a helper factor(s) with T-cell-replacing activity in synovial fluid. AB - Cell-free synovial fluid (SF) obtained from patients with rheumatoid arthritis contains a helper factor(s) capable of augmenting the generation of plaque forming cells (PFC) in pokeweed mitogen (PWM)-stimulated normal peripheral blood mononuclear cells (PBMC). This helper factor behaves like a polyclonal B-cell activator, in that it triggers the formation of IgM, IgG, and IgA PFC. However, SF has little or no effect on the proliferation of PWM-activated PBMC. Furthermore, SF was capable of replacing T cells for PWM-induced differentiation but not proliferation of enriched human blood B lymphocytes. No helper factor or T-cell-replacing activity was found in SF from patients with traumatic synovitis. Fractionation of SF containing helper activity on staphylococcal protein A column indicated that the activity is induced by biologically active molecules distinct from materials that preferentially bind to protein A such as IgG immune complexes. We conclude that the present activity has striking similarities to the recently described B-cell differentiation factor that is produced by specifically activated T-cell lines in vitro. PMID- 6240114 TI - [Atripeptins]. PMID- 6240115 TI - Molecular markers of platelet activation. PMID- 6240116 TI - Platelet-released proteins as molecular markers for the activation process. AB - The desire to have a specific, sensitive marker for platelet activation was originally thought to lie in the development of RIAs for BTG and PF4. Although this wish has not been denied, the interpretation of the information obtained from such an analysis has proved far less rewarding. The principal challenge of these procedures is based upon the lack of a cause and effect relationship between a given disease and platelet activation, coupled with the differential clearance rate and mechanism for each of the discussed proteins. Thus, we have seen that the renal clearance rate and mechanism for each of the discussed proteins. Thus, we have seen that the renal clearance of a patient should be noted prior to interpreting the elevation of BTG. Similarly, since PF4 is removed from the circulation so rapidly, its plasma values tend to be lower than BTG by a factor of 5, although the significance of the BTG to PF4 ratio is questioned. Administration of heparin results in a heparin-induced increase in plasma PF4 levels but not for BTG, and this PF4 increase can be as great as 20-fold. PF4 and BTG values are also directly increased by pressure increases. Taken individually, these mediators each compromise the ability to correlate the significance of platelet protein increases with any single pathologic condition. When viewed collectively, an analysis of platelet-released proteins is best interpreted as an indication that the functional integrity of the platelet has been perturbed; the direct relationship of disease processes to platelet release is far from certain and is simply documented by the use of such described procedures. The final note of caution for these assays is to be found in the recent summary analysis of the standardization of both BTG and PF4. In this study, considerably greater variation among laboratories was noted for PF4 than was seen for BTG, and the study directors concluded that comparisons of results between laboratories should be regarded as unreliable due mainly to the use of different standards for each protein in a given laboratory. The final note of caution for these assays is to be found in the recent summary analysis of the standardization of both BTG and PF4. In this study, considerably greater variation among laboratories was noted for PF4 than was seen for BTG, and the study directors concluded that comparisons of results between laboratories should be regarded as unreliable due mainly to the use of different standards for each protein in a given laboratory. PMID- 6240117 TI - Laboratory application of radioimmunoassay in the quantitation of molecular markers of hemostatic activation. PMID- 6240118 TI - Loss and grief: handicapped children and their families. PMID- 6240119 TI - [Teaching methods of the physical examination of patients]. PMID- 6240120 TI - [Training of dental hygienists]. PMID- 6240121 TI - [Functional activity of thymic subpopulations]. PMID- 6240122 TI - [Clinical manifestations of lymphoproliferative disorders of thymic origin]. PMID- 6240123 TI - Fibrinolysis: molecular mechanism and pathophysiological aspects. PMID- 6240124 TI - Workers' compensation: coverage, benefits, and costs, 1982. AB - Workers' compensation provides medical care and income maintenance protection to workers disabled from work-related injury or illness. This program is of considerable interest to the Social Security Administration (SSA) from several perspectives. For example, since 1965 Social Security Disability Insurance (DI) benefits and workers' compensation payments have been integrated. Information on the experience under workers' compensation provides a framework for examining questions concerning gaps and overlaps in the Nation's social insurance system. In addition, since December 1969 SSA has administered claims filed through 1973 under part B of the Black Lung program--the program providing income maintenance protection to coal miners disabled by pneumoconiosis. The workers' compensation experience reported here consists of information on benefits for work-related injury and disease, including data on the combined benefits paid under the entire Federal Black Lung program administered by the Labor Department and SSA. PMID- 6240125 TI - Depression in the geriatric population--implications for the dental practitioner. PMID- 6240126 TI - Nasogastric intubation--oral and perioral care. PMID- 6240127 TI - Adrenal insufficiency: report of case. PMID- 6240128 TI - A fixed-removable prosthesis for use in handicapped individuals. PMID- 6240129 TI - [Use of graded bicycle ergometry as a method for the objective evaluation of the efficacy of reflexotherapy in the early stages of hypertension]. AB - Graded bicycle ergometry was used to evaluate the efficacy of pathogenetic auriculo-paravertebral reflexotherapy (RT) in 24 patients with stages IB and IIA of essential hypertension (EH). After RT was completed the subjective symptomatology, central hemodynamics, and heart work improved. The increment of the minute volume of the circulation in response to graded exercise decreased, especially in patients with stage IB of EH. These patients also showed a reduction in the heart rate. The total peripheral vascular resistance dropped both at rest and after exercise. After RT the patients with stages IB and IIA of EH manifested a decrease in the loading heart index and intensity of the functioning of the structures, with that decrease being more demonstrable in patients with stage IIA EH, which attested to the lowering of heart muscle oxygen consumption. The decreased intensity of the functioning of the structures in patients with stage IB EH points to the diminution of myocardial hyperfunction marking the hyperkinetic circulatory pattern in these patients. PMID- 6240130 TI - Positioning of the cerebral palsy patient to facilitate dental treatment. PMID- 6240131 TI - Cardiovascular birth defects and antenatal exposure to female sex hormones: a reevaluation of some base data. AB - A re-evaluation of the base data as reported by Heinonen et al. from the Drug Epidemiology Unit of the Boston Collaborative Perinatal Project (CPP) was undertaken in order to examine particularly three matters which were not fully considered in the publication. These were, first, the timing of administration of sex hormones during the index pregnancy, which is relevant to determining whether any statistical association reported between sex hormone exposure and malformations could be causal; second, the incidence of serious maternal vaginal bleeding in early pregnancy, which could be an indication of threatened abortion, which in turn is associated with an increased malformation rate, and in addition is an indication for sex hormone administration; and third, the incidence of malformations or other adverse outcome in previous pregnancies, which, if present, might play a material role in the risk of malformation in the index pregnancy. Examination of the records of the 19 cases described by Heinonen et al. as hormone-exposed/cardiac-malformed revealed that no preparation containing hormone was administered in two patients, that five cases were given hormones too late in the index pregnancy to have any effect on cardiac organogenesis (which by general consensus begins on day 19 and ends at the latest on day 50 of gestation), that two cases were given hormones too early and two cases had Down's Syndrome. Thus eight children were exposed to hormones during the critical period of cardiac organogenesis, out of 17 actual hormone takers (47%). The description of vaginal bleeding did not allow any conclusions regarding differential rates of threatened abortion. It was found that the incidence of major malformations was 17% in the index group and 4% in the non-malformed group. This suggests that the hormone-exposed patients who gave rise to children with cardiac malformations were a highly selected group. The re-evaluation therefore reveals that the incidence of exposure to sex hormones during the critical period of cardiac organogenesis was not significantly different statistically in those women whose children had cardiac lesions as compared to those without such lesions. It is suggested that the result of this re-evaluation should direct the attention of epidemiologists to the quality of their base data. Re-examination of the base data of the Boston CPP does not support their reported association between the exposure to female sex hormones during pregnancy and the occurrence of cardiac malformations. PMID- 6240132 TI - Federal workers' disability program and the private physician. PMID- 6240133 TI - A method to minimize platelet activation during platelet isolation. PMID- 6240134 TI - Dentists' nightmare: that aching back! PMID- 6240135 TI - Optimum cell numbers for mixed lymphocyte responses in hanging-drop microcultures. AB - The conditions required for optimum mixed lymphocyte culture (MLC) responses in hanging-drop (HD) microcultures in Terasaki trays have been investigated. Compared with conventional (200 microliter) MLC, HD-MLC required 5-10 times fewer cells, and 10% of the amount of culture medium and 3H-thymidine label. Peak uptake of label in HD-MLC was mutually responder-stimulator concentration dependent. Differences in response to related and unrelated lymphocytes indicate that HLA-D determinants are detected in HD-MLC. PMID- 6240136 TI - [Dental morbidity in schoolchildren with varying states of health]. PMID- 6240137 TI - [Hygienic instruction and the education of children in a Pioneer camp]. PMID- 6240138 TI - [Up-to-date forms and methods of health education work for the pedodontist]. PMID- 6240139 TI - [Organization of prophylactic work in the Pedodontics Department of the Klaipeda Dental Polyclinic, Lithuanian SSR]. PMID- 6240140 TI - [Outlook for the development of pedodontics in the USSR]. PMID- 6240141 TI - [Epidemiological characteristics of maxillodental anomalies in children living in the northern European part of the USSR]. PMID- 6240142 TI - [Results of the local prevention of dental caries in schoolchildren]. PMID- 6240143 TI - [100th anniversary of the S. M. Kirov Leningrad State Order of Lenin Institute for the Advanced Training of Physicians and the 60th anniversary of the Department of Forensic Medicine]. PMID- 6240144 TI - [Symptomatic atlanto-axial dislocation in Down's syndrome]. PMID- 6240145 TI - [A uterine guide to gynecologic laparoscopy]. PMID- 6240146 TI - [Allergy to penicillin: a practical guide for the general practitioner]. PMID- 6240147 TI - Primary biliary cirrhosis--phenotypic characterization of immunocompetent cells in peripheral blood and liver tissue. AB - Circulating T-cell subsets have been characterized in 18 patients with primary biliary cirrhosis (PBC) using a simple immunoenzymatic staining method on stored and prefixed cell samples. Furthermore, a double immunoenzymatic method was used to study T-cell subsets and their relationship to HLA-DR+ cells in frozen sections of liver biopsies from 12 patients with PBC. In 10 cases blood and liver samples were taken simultaneously from the same patient. Patients with PBC of early histological stage showed an elevated absolute number of helper/inducer T cells (Leu 3a+) and reduced relative percentages of suppressor/cytotoxic T-cells (Leu 2a+) compared with healthy subjects resulting in an elevated helper/suppressor ratio. Liver biopsies in PBC were dominated by helper inducer phenotype T-cells in all cases irrespective of histological stage, penicillamine treatment or the relative levels of circulating T-cell subsets. A relatively high amount of HLA-DR+ cells were seen, several of these in close approximation to T cells. PMID- 6240148 TI - The presence of normal levels of serum immunoreactive insulin-like growth factor 2 (IGF-2) in patients with Down's syndrome. AB - The present study was performed to further investigate the levels of somatomedins in Down's syndrome (DS). The results show that the serum levels of immunoreactive insulin-like growth factor 2 (RIA-IGF-2) in patients with DS is within the normal adult range. No age variation among the patients was observed. Since we earlier reported a deficiency of immunoreactive insulin-like growth factor 1 (IGF-1) in DS patients, present study showing normal RIA-IGF-2 levels suggests a selective deficiency of IGF-1 in DS. PMID- 6240149 TI - Prostatic origin of fucosyl transferase in human seminal plasma--a study on healthy controls and on men with infertility or with prostatic cancer. AB - Fucosyl transferase was recovered in soluble form in human seminal plasma. The enzyme had very little activity, as it was structurally bound to prostasomes, which are membrane-surrounded organelles in seminal plasma. The fucosyl transferase activity was recorded on Sephadex G200 chromatography of seminal plasma (supernatant after ultracentrifugation) in one single peak coinciding with that of prostate-specific acid phosphatase. Studies on healthy men and on men with prostatic cancer suggest a prostatic origin of fucosyl transferase activity; two of the men with prostatic cancer displayed 50-95% decreased activities. Antiandrogenic therapy in another man with cancer resulted in substantial reductions in seminal plasma contents of fucosyl transferase, ATPase, acid phosphatase and fructose suggesting a role of testosterone in their secretions. PMID- 6240150 TI - The effect of previous endocrine therapy on responses to a single dose of an LHRH analogue. AB - Serum concentrations of gonadotropins, testosterone and dehydrotestosterone were determined in patients receiving conventional endocrine therapy for advanced metastatic adenocarcinoma of prostate. The effect over 4 h of a single dose of a long acting analogue of LHRH was determined in these patients and compared to the response in patients receiving the analogues as first choice of treatment. Oestrogen therapy was found to suppress basal and stimulated gonadotropins and testicular androgens. Cyproterone therapy only partially reduced basal hormone concentrations and the response to the LHRH analogue was delayed. Orchidectomy resulted in elevated gonadotropins and an exaggerated response to the analogue. As patients who relapse while failing conventional therapy, may subsequently be treated by further endocrine manipulation, precise determination of their endocrine status should predict any expected benefit. Patients previously treated with stilboestrol are unlikely to respond to orchidectomy or LHRH analogue. PMID- 6240151 TI - [Experience with the restorative treatment of locomotor injuries at an outpatient rehabilitation center]. AB - The article analyzes the experience with the treatment of 960 trauma patients in the restoration department of the out-patient clinic and makes an assessment of some organizational and clinical aspects of its activities. High percentage of favorable results (95,9%) was shown by late follow-up of the patients after injuries. Bad results were found in 4,1% of cases, 5,4% of the patients had temporary invalidism. A conclusion is made that the efficiency of the treatment in the restoration department may be improved by eliminating some problems of organizational character. PMID- 6240152 TI - [Department and Clinic of Hospital Surgery for Interns of the 1st Pavlov Leningrad Medical Institute. An interview with Academician of the Academy of Medical Sciences of the USSR F. G. Uglov (by E. I. Zaitsev)]. PMID- 6240153 TI - Parasitological, serological and clinical effects of continuous graded levels of Dictyocaulus viviparus inoculations in calves. AB - To investigate the parasitological, serological, clinical and growth effects of continuous graded levels of Dictyocaulus viviparus inoculations in calves an experiment was carried out with 10 groups of 5 calves each. Calves were inoculated twice a week during a period of ten weeks. The range of the doses was 10-2560 infective larvae (L3) per inoculation. The results were analysed by linear and curvilinear regression of various traits on infection level. It is concluded that: A continuous exposure of calves to L3 of D. viviparus was followed by a continuous larval excretion at all levels; Results of the ELISA technique gave a very good reflection of the level of infection; Clinical signs and weight loss were evident before the parasitological and serological results were positive; The serological parameter and the parasitological parameters were mainly linearly related to the level of infection. The clinical parameters were mainly cubically related to the level of infection. PMID- 6240154 TI - Purification and properties of gene 18 product of bacteriophage T3. AB - Two noncapsid proteins of T3 and T7 phage, the products of gene 18(gp18) and gp19, are required for DNA packaging. By using in vitro complementation for DNA packaging as an assay system, T3 gp18 was purified to near homogeneity from an extract prepared cells infected with a mutant of gene 19(19- extract). The purified gp18 consisted of a single polypeptide having a molecular weight of 10,000, and was eluted as dimers and higher multimers from Sephadex G-75 columns. T7 gp18 was purified by the same procedures as that for T3 gp18 and behaved in the same manner as T3 gp18 throughout all purification steps. Gp18 from either T3 or T7 phage complemented both T3 and T7 18- extract for DNA packaging. These results indicate that, in contrast to gp19 [H. Fujisawa and M. Yamagishi (1981) Prog. Clin. Biol. Res. 64, 239-252], gp18 does not have specificity for T3 or T7 DNA during the in vitro packaging reaction. T3 gp18 was purified from extract containing functional gp19. The gp18 copurified with the gp19 activity. Gp18 and gp19 activities were stable when they were copurified but were unstable when purified separately. These results suggest that gp18 and gp19 function as a complex in the DNA packaging process. The gp18-gp19 preparation had a prohead stimulated, DNA-dependent ATPase activity. PMID- 6240155 TI - [Local immunity of the upper respiratory tract in patients with acute leukemia]. AB - The paper discusses the data on secretion of immunoglobulin and lysozyme in the upper respiratory tract of patients with acute leukemia. The data were used in the evaluation of certain biological preparations intended for prevention of infectious complications. PMID- 6240156 TI - [Organization of the health care of patients with breast cancer]. AB - The paper discusses the 5-year experience of operation of cancer control service provided at a hospital department with a capacity of 50 beds as well as the results of two out-patient mammological screenings conducted by the Dispensary staff. Coordination of this work yielded a unified approach to the diagnosis and treatment of precancer and cancer of the breast. It also ensured continuity in application of procedures of therapy and prophylactic medical examination in the entire cancer control service of the Region. As a result, early diagnoses of breast cancer have become more reliable and treatment of precancerous lesions has improved. PMID- 6240157 TI - [Activity of non-specific T-suppressors regulating the proliferation of B- and T lymphocytes in patients with fibroadenomatosis, breast cancer and stomach cancer]. AB - A decrease in proliferative rate of blood-circulating lymphocytes in response to LPS and PHA was registered in patients with fibroadenomatosis and cancer of the breast and stomach cancer. The said cells preincubated with Concanavalin A showed a weak inhibitory action on B-cells. The inhibition of T-cell proliferation by lymphocytes either remained unchanged or became less apparent in stage II breast cancer and slightly increased in stage III gastric cancer. Since no correlation was established between proliferative levels of T- and B-lymphocytes, two separate subpopulations of non-specific lymphocytes (T-T and T-B) were suggested. PMID- 6240158 TI - [Niacin metabolism in the rat after administration of large doses of folic acid]. AB - Administration to rats of large doses (500 mg per kg bw) of folic acid did not exert any effect on daily excretion of N'-methyl nicotinamide with urine on days 10, 15 and 20 of experiment and raised 1.5-fold the content of nicotinamide nucleotides in the blood by day 20 of experiment as compared with respective parameters in the control animals. The content of nicotinamide nucleotides in the liver increased 1.37-and 1.81-fold on days 15 and 20 of experiment, respectively. PMID- 6240159 TI - [Prevention of dermatitis and eczema in industrial enterprises]. PMID- 6240160 TI - [Effect of splenin on the blood T-lymphocyte count in workers in the manufacture of amino acids and antibiotics]. PMID- 6240161 TI - [New data in the study of slow virus infections]. PMID- 6240162 TI - [Diagnostic difficulties in renal cancer (2 cases of clear-cell carcinoma)]. PMID- 6240163 TI - [Measurement of urinary flow velocity and peak flow rate in the detection of subvesical obstructions in boys]. AB - Urinary flow velocity and urinary peak flow rate were measured in 41 boys. Using combined urodynamic and radiological methods 23 boys showed proximal and/or distal urethral obstruction, whilst 18 boys had no signs of subvesical obstructions. The peak flow rate alone does not discriminate reliably between the normal and abnormal population. Many boys with normal flow rates showed subvesical obstruction on measurement of the peak urinary velocity. In spite of the fact that flow velocity determination alone only partially discriminated between the different groups, in combination with uroflowmetry it proved to be a valuable secondary non-invasive parameter. The flow velocity vs. flow rate diagram is shown to be a good tool for the urodynamic classification of boys with subvesical obstruction. PMID- 6240164 TI - Cellular immune findings in Lyme disease. AB - From 1981 through 1983, we did the first testing of cellular immunity in Lyme disease. Active established Lyme disease was often associated with lymphopenia, less spontaneous suppressor cell activity than normal, and a heightened response of lymphocytes to phytohemagglutinin and Lyme spirochetal antigens. Thus, a major feature of the immune response during active disease seems to be a lessening of suppression, but it is not yet known whether this response plays a role in the pathophysiology of the disease. PMID- 6240165 TI - [Effectiveness of hand-protective salves in urea contamination]. PMID- 6240166 TI - [Internal versus topical tetracycline therapy of acne]. AB - The study comprised 49 patients suffering from acne who were treated over a period averaging 4.7 +/- 1.2 months with tetracyclines administered either orally (1000 mg daily for 5 days, then 250 mg daily) or locally (2% alcoholic solution). Randomization was carried out by means of random numbers. The percentage of pustules among the total acne efflorescences was chosen as clinical parameter for the efficacy of the antibiotic therapy. After treatment, both collectives showed the same significant decline of pustulation. The therapy was finally evaluated on a six-point scale both by the doctor and the patient. In total, there could not be detected any significant difference in the evaluation of local and oral medication. PMID- 6240167 TI - [Determination of the size of the right atrium in patients with pulmonary hypertension using 2-dimensional echocardiography]. AB - Normal values for right atrial area and tricuspid annular diameter and their percentage shortening measured from the two-dimensional echocardiographic four chamber view are now available. In this study right atrial size of patients with pulmonary hypertension is evaluated and the results compared with the M-mode findings of the right ventricle in order to detect pulmonary hypertension. Hemodynamics and echocardiograms of 60 patients (mean age 57 +/- 10 years) with mitral stenosis III-IV NYHA and concomitant pulmonary hypertension were examined. 20 patients in group I with atrial fibrillation had additional functional tricuspid incompetence. Unlike the 20 patients in group II, who had atrial fibrillation, the remaining 20 in group III were still in sinus rhythm. The mean pulmonary artery pressure was 44.1 +/- 9.3 mmHg in group I, in group II 33.9 +/- 6.3 mmHg (grp. I vs. grp. II p less than 0.001) and in group III 33.2 +/- 7.1 mmHg (grp. II vs. grp. III ns). The end-systolic index of the right atrial area in group I was 19.6 +/- 5.7 cm2/m2 and thus significantly greater than in group II with 10.6 +/- 2.3 cm2/m2 (p less than 0.001) and in group III with 9.1 +/- 2.5 cm2/m2 (p less than 0.001). The maximal diameter of the tricuspid annulus measured 24.6 +/- 5.5 mm/m2 in group I, 18.9 +/- 3.5 mm/m2 in group II (grp. I vs. grp. II p less than 0.001) and 20.2 +/- 2.2 mm/m2 in group II (grp. I vs. grp. II p less than 0.001) and 20.2 +/- 2.2 mm/m2 in group III.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 6240168 TI - [Extraction of a broken intracoronary PTCA guide wire perforating the circumflex artery, using a Dotter retrieval catheter]. AB - Coronary artery perforation is a rare but potentially lethal complication during percutaneous transluminal coronary angioplasty (PTCA). To avoid pericardial tamponade, it has been suggested that perforating wires or balloons should not be withdrawn and that the patient should be transferred immediately to surgery. We report a case with a perforating and broken intracoronary guide wire which was successfully extracted using a Dotter intravascular retriever catheter. The only consequence was a small pericardial effusion not requiring pericardial puncture. Thus, emergency surgery is not inevitable after coronary artery perforation caused by thin intracoronary guide wires. PMID- 6240170 TI - [T-lymphocyte subpopulation in the peripheral blood of patients with psoriasis]. PMID- 6240169 TI - Dose rate dependence of radiation induced IgG membrane receptor alteration [1]. AB - Mouse lymph node lymphocytes are irradiated at different dose rates and the B cell receptors to anti IgG are tested. The expression of receptors is inhibited by irradiation. It is shown that the effectivity of irradiation increases with decreasing dose rate suggesting that membrane damage may be important for situations of chronic irradiation or implant radiotherapy. PMID- 6240171 TI - [Trichophyton gallinae as a causative agent of trichophytosis in birds and humans]. PMID- 6240172 TI - [Staphylococcal and toxic "burned skin" syndromes]. PMID- 6240173 TI - [Effect of industrial oils of Apsheron on the sebaceous-hair system of the skin in workers]. PMID- 6240174 TI - [Enzymes and iontophoresis]. PMID- 6240175 TI - [Hydrothermal baths of Spa, acid-base equilibrium and blood oxygen as seen by the clinician]. PMID- 6240176 TI - [Manual medicine: an ancient discipline with a future]. PMID- 6240178 TI - [Electric currents used for dielectrolysis]. PMID- 6240177 TI - [Manual medicine and the extremities: treatment principles]. PMID- 6240179 TI - [Properties of unidirectional currents]. PMID- 6240180 TI - [Accidents and complications in iontophoresis: their prevention]. PMID- 6240181 TI - [Contact eczema and drug ionization]. PMID- 6240182 TI - Human immunoregulation. An overview. PMID- 6240184 TI - [Chromosome aberrations in human cultured lymphocytes induced by neocarzinostatin]. PMID- 6240185 TI - The Accessible Housing Society. PMID- 6240183 TI - Influence of streptozotocin- and alloxan-induced diabetes on the metabolism of glycosaminoglycans. AB - GAG metabolism was investigated in rats with experimentally induced diabetes. In comparison to control animals, the uptake of 35S-sulfate was diminished in tissues of diabetic animals. Streptozotocin-induced diabetes showed a significant decrease in the content of GAG fractions except that of non-sulfated GAG in liver and kidney which was unchanged as compared to the control group. In rats rendered diabetic by alloxan, non-sulfated GAG increased appreciably in liver and kidney whereas highly sulfated GAG remained unchanged. In the skins of alloxan-diabetic rats both total and sulfated GAG decreased significantly. The activities of liver beta-glucuronidase, beta-N-acetyl glucosaminidase and cathepsin D were significantly increased in rats treated with streptozotocin and alloxan. In streptozotocin-diabetic rats, renal beta-glucuronidase and beta-N-acetyl glucosaminidase activities were reduced while cathepsin D activity was similar to that of controls. The renal beta-N-acetyl glucosaminidase and cathepsin D activities of alloxan-treated rats were not significantly different from normal but their beta-glucuronidase was significantly increased. In the spleen of streptozotocin-diabetic rats all the enzymes were increased except beta-N-acetyl glucosaminidase which remained unaltered. Increased excretion of uronic acid was observed in diabetic groups. These results collectively indicate that both streptozotocin- and alloxan-induced diabetes altered the synthesis and catabolism of GAG. PMID- 6240186 TI - Histochemical fiber composition of lumbar back muscles in the rabbit. AB - The present study of the back muscles of the rabbit, using enzyme histochemical techniques and stereological methods, was undertaken with the view to gaining a better understanding of the fiber-type make-up of the lumbar musculature of this animal. The muscles considered were the multifidus, sacrospinalis and the intertransversarii between levels L5 and L6. Gross examination reveals that the multifidus and the sacrospinalis form the bulk of the lumbar musculature and that these muscles appear white. Between and deep to these two muscles are the red intertransversarii. Histochemically the multifidus and the sacrospinalis are also similar in their fiber-type composition, mostly types IIA and IIB and the percentage of connective tissue that they contain. The intertransversarii, in contrast, are for all practical purposes composed of only type-I fibers. The intertransversarii contain significantly more connective tissue than the other two muscles. It may be concluded that the bulk of the lumbar musculature of the rabbit is phasic while the intertransversarii, containing only type-I fibers and a high percentage of connective tissue, are postural muscles. PMID- 6240187 TI - Interaction of thermally aggregated human IgG with bacteria. AB - Ninety-three bacterial strains, representing 16 Gram-positive and Gram-negative species, were tested for quantitative binding of 125I-labelled monomeric and thermally aggregated human IgG. Aggregated IgG bound to all bacterial species studied, in contrast to monomeric IgG, which interacted only with S. aureus, group A, C and G streptococci, viz. bacteria possessing previously described IgG Fc receptors. A positive correlation was observed between binding of monomeric IgG and the uptake of thermally aggregated IgG (r = 0.92). Monomeric IgG inhibited effectively the binding of monomeric IgG but only partially the uptake of aggregates. Absorption with bacteria revealed that only a fraction of aggregated IgG could interact with bacteria lacking specific IgG-Fc receptors. A human group G streptococcus strain (G-148), tested with increasing amounts of immunoglobulin, was capable of binding at least ten times as much aggregates as monomeric IgG, implying binding to separate binding sites. These data indicate that polymeric IgG produced by thermal aggregation of human polyclonal IgG can interact with bacterial surface components found in most pathogenic microorganisms. This interaction seems to be less specific than the binding to previously described IgG-Fc receptors. PMID- 6240188 TI - Change in surface area of zimeldine dihydrochloride hydrate on storage. PMID- 6240189 TI - Cardiopulmonary blood volume during acute blood pressure elevations in dogs. AB - During aortic blood flow obstructions and angiotensin infusion blood may be accumulated in the heart and the lungs because of retention or redistribution of blood from compliant regions. We measured the cardiopulmonary blood volume (CPBV) when left ventricular systolic pressure was raised by about 50 mmHg by angiotensin infusion and by balloon inflation in the ascending and descending thoracic aorta, at control inotropy and during isoproterenol infusion, in 6 anesthetized, closed-chest dogs. CPBV was calculated from determinations of cardiac output (thermodilution) and the interventricular mean transit time of ascorbate (polarographic determination). Angiotensin always increased CPBV, but the rise was greater at high than at control inotropy (16.5 +/- 4.4% and 5.1 +/- 1.2%). Balloon inflation in the descending thoracic aorta increased CPBV similarly at high and control inotropy (11.1 +/- 2.4% and 16.6 +/- 4.0%) whereas CPBV was unaltered or fell during inflation in the ascending aorta at both inotropic levels. Right and left ventricular end-diastolic pressures rose only during angiotensin infusion and balloon inflation in the descending thoracic aorta. By balloon inflation, cardiac output only fell during blood flow obstruction in the ascending aorta. Thus, an increase in CPBV during these interventions is not due to retention but is caused by redistribution of blood towards the heart. PMID- 6240191 TI - Suppressive influence of surgical stress on the graft-versus-host reaction in mice. AB - The influence of surgical stress on the local graft-versus-host reaction (GVHR) in F1 mice was studied. Skin incision 1 day prior to injection of parental spleen cells produced impairment of popliteal lymph node enlargement; however, this effect was not observed when GVHR was induced 3 and 5 days after operation. Strong GVHR suppressive activity of spleen cells was observed three hours after leg amputation before a decrease in thymus weight became evident. The GVHR suppressive activity declined by six hours later, but a second peak of 60% inhibition was observed after 24 h. This suppressive activity completely disappeared by treatment with anti-Thy 1.2 and complement. This shows that the GVHR is suppressed by surgical stress, and that this suppression is due to suppressor T lymphocytes. PMID- 6240190 TI - The dopamine D-1 antagonist SCH 23390 inhibits apomorphine but not pergolide induced rotation. PMID- 6240192 TI - Venous volume in offspring of hypertensive patients. AB - Twenty normotensive healthy male offspring of hypertensive patients were compared to 20 adequate controls regarding venous volume, the effect of ouabain on venous volume and signs of left ventricular hypertrophy. Among offspring there were slightly increased amplitudes in the orthogonal ECG as compared to controls but the differences were not statistically significant. Using a plethysmographic technique we found a significantly lower venous volume of the forearm in the offspring than in controls. There was, however, no effect of ouabain on the venous volume. The decreased venous distensibility among normotensive offspring might be an early manifestation of essential hypertension. PMID- 6240193 TI - On the normal scalar ECG. A new classification system considering age, sex and heart position. AB - 472 randomly selected men and women from the city of Lund were examined for disease in the heart, lungs and for hypertension. 163 men and 194 women who had no symptom or sign of disease were accepted for the further study. The prevalence of various exclusion criterias, such as symptoms and signs of heart disease, lung disease and other diseases which may possibly affect the ECG are reported as well as the distribution of blood pressures in the sample. A computer-averaged standard 12-lead ECG (leads aVL, I, -aVR, II, aVF, III, V1-V6) was recorded. All measurements of ECG-deflections have been made visually using a magnifying glass (6 times). ST-segments were classified according to the Punsar code by independent visual observers as well as by the computer. The mean frontal QRS axis shifted to the left with advancing age, but the shift was statistically significant only in men. In both men and women there was a leftward shift of the mean frontal QRS-axis with increased weight, increased chest circumference and increased obesity index. The normal range of axis was found to be 0 degrees to 90 degrees in men and +15 degrees to 90 degrees in women. The problems concerning the definition of the electrical heart position is discussed. The concept of a Q axis is introduced as an alternative way to indicate electrical heart position. There is a statistical significant relationship between the Q-axis and the QRS axis in the frontal plane, although this relationship is not always apparent in the individual ECG. The presence or absence of a Q-wave in an individual lead was used to denote a lead as being a left ventricular lead or not. Using the Q-wave as a marker of heart position in the individual lead is more practical than to use the QRS-axis or the transitional zone. Duration and amplitude of the Q-wave have been measured. The upper limit of normal duration exceeded 0.03 s in leads aVL and aVF in men but not in women. The R-wave amplitudes proved to vary with age and heart position in men. In women variation of the R-wave amplitude was found with heart position but not with age.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 6240194 TI - Predictive value of radiculography in patients with lumbago-sciatica. A prospective study (Part II). AB - One hundred patients with symptoms of lumbo-sacral root compression were prospectively and consecutively assigned to operation based alone on clinical findings. A preoperative myelogram was performed in all patients and described without a knowledge of the clinical features. All patients were explored for the clinically and myelographically relevant disc. When the myelogram was normal (16 patients) both lower lumbar interspaces were exposed. In 58 patients a herniated disc was revealed at surgery. Only "myelographic herniation" with indentation of the contrast column was accompanied by a high frequency of disc herniation at surgery (73-87%). In cases with normal myelograms only 5% had a disc herniation. The severity of the myelographic finding was clearly correlated to the frequency of positive surgical findings and good outcomes. The preoperative radiculogram gives a high degree of certainty in the preoperative evaluation whether a surgical lesion is present or not and reveals a precise prediction of the outcome of surgery. PMID- 6240195 TI - Acne: an approach to therapy for the pediatrician. PMID- 6240196 TI - Clinical disorders associated with T cell subset abnormalities. AB - Monoclonal antibodies have been used to enumerate T cell subsets in many different diseases, only a portion of which have been reviewed here. These studies have increased our understanding of T cell immunoregulation in these diseases. In the future, other diseases will similarly be analyzed regarding their immunoregulatory T cell defects. That different investigators have reported conflicting results regarding the same disease is not unexpected. Different patients at different stages of the same disease may not always have the same T cell abnormalities. Patient subgroups with different etiologies and prognoses may well have different T cell subsets. Many of the diseases described in this chapter with decreased T suppressor-cytotoxic cell number and function are associated with autoimmune or autocytotoxic disorders. The lack of T cell suppressor activity may result in a lack of regulation of both autoantibody production and autocytotoxic activity. Increased T cell suppressor-cytotoxic cell numbers have been found in certain viral infections, such as EBV, CMV, and HBV. Other viral agents may produce similar changes in T cell subsets as the immune system attempts to clear and combat these agents. These virus-induced changes in the immune system may be responsible for the transient immunosuppression observed in several of these illnesses. Decreased T helper cell number has been observed in transient hypogammaglobulinemia of infancy. This common pediatric problem seems to result from an immature or delayed development of T helper cell activity. The disease is a transient one, and return to normal gammaglobulin synthesis occurs with the return of normal T helper cell numbers. Increased T helper cell number seems to occur in diseases with excessive immune activity, such as sarcoidosis and granuloma annulare. This excessive activity of T helper cells may be responsible for the disease manifestations. In the future, one can expect more studies regarding T cell subset abnormalities in a wide variety of diseases. Cure and therapy of many diseases may be monitored in the future by T cell subset abnormalities. This will be a most exciting area in the future for pediatrics. PMID- 6240197 TI - Implantable infusion pumps. PMID- 6240198 TI - Treatment of abdominal wall eventrations associated with abdominoplasty techniques. AB - An experimental and clinical study using alloplastic materials (Marlex and Prolene mesh) for repairing large defects of the abdominal wall is reported. A defect was created in the experimental model to simulate an anatomical disarrangement of the musculo-aponeuroticfascial complex of the abdominal wall and the surgical correction of this deformity. Macroscopic and microscopic observations of the operated area were done to demonstrate the good integration of the surrounding tissues with the mesh. In a clinical study, 16 patients, presenting large eventrations of the abdominal wall, were surgically treated using Marlex or Prolene mesh to reinforce the abdominal wall. Two techniques of abdominoplasty, vertical and horizontal, were performed on these patients, according to the location of previous scars. The advantages of using alloplastic materials to reinforce the abdominal wall and the cosmetic results of both abdominoplasty techniques are discussed. PMID- 6240199 TI - First-trimester prenatal diagnosis of Tay-Sachs disease. AB - The prenatal diagnosis of Tay-Sachs disease was made in two at-risk fetuses by the analysis of chorionic villi obtained at 9 and 11 menstrual weeks, respectively. The diagnoses were based on the absence of beta-hexosaminidase A activity as determined by: (1) specific enzyme assays, (2) anion-exchange chromatography, and (3) cellulose acetate gel electrophoresis. The enzymatic diagnoses were confirmed on fetal tissue as well as by ultrastructural demonstration of the first-trimester fetal neuropathology. Optimal assay conditions for beta-hexosaminidase A in chorionic villi were established for the prenatal diagnosis of Tay-Sachs disease. Importantly, it was noted that a small amount of decidua or maternal blood could lead to misdiagnosis. Thus, extreme care must be taken in the preparation of chorionic villi for Tay-Sachs as well as other prenatal metabolic diagnoses. PMID- 6240200 TI - Genetic polymorphisms among Bukharan and Georgian Jews in Israel. AB - Bukharan and Georgian Jews have lived in central Asia for many centuries. Approximately 30,000 Bukharan and 37,000 Georgian Jews lived in their respective countries within the USSR between 1920 and 1960. Genetic markers of blood--blood groups, isoenzymes, HLA antigens, and gamma and kappa chain allotypes--were tested in blood samples from 113 Bukharan and 134 Georgian Jews living in Israel. Estimates of inbreeding were low: alpha = 0.0088 for Bukharan and alpha = 0.0011 for Georgian Jews. G6PD deficiency was relatively rare in Bukharan (2.2%) and in Georgian Jews (6.0%), when compared to other Jews in the area. Both populations showed frequencies of some markers similar to that of other Jewish populations, but frequencies of several markers were extremely high or low. Bukharan Jews showed very high frequencies of B(0.243), cDe (0.122), JkA (0.705), HLA-A29 (0.167), A30 (0.116) and B7 (0.124), and AcPA (0.451) and very low ones of O(0.518), CDe(0.422), AcPB (0.513) and GLO1 (0.140). Very high frequencies in Georgian Jews were observed for cDE (0.189), HLA-A3 (0.194), Bw35 (0.300) and GLO1 (0.367). Yet the greatest difference between both populations was in African characters. While in Bukharan Jews Fy was very frequent (0.146) and cDe was the highest observed among Jews (0.122), neither of these markers was detected among the Georgian Jews tested. Yet, another African character, the Gm1,5,10,11,13,14,17,26 haplotype, occurred in both populations (0.028 and 0.042 in Bukharan and Georgian Jews, respectively). Distance measures for Bukharan, Georgian, Iranian, Cochin, and Libyan Jews based on 13 polymorphic loci showed the greatest distance between Cochin Jews and the other populations and the smallest distance between the Georgian and Iranian Jews. PMID- 6240202 TI - Mental development of adults with Down syndrome. AB - Measures of cognitive, verbal, and functional performance obtained at widely separated time periods were examined for adults with Down syndrome. Comparisons of first and last test profiles for Raven Coloured Progressive Matrices, Peabody Picture Vocabulary Test, and Adaptive Functioning Index (Social Education) Test all demonstrated significant increases over a mean time span of 5 years. These increases could not be attributed to year of entry into program, history of institutionalization, or age of the individuals. The findings indicate that mental development of adults with Down syndrome continues well into the third and fourth decade of life. PMID- 6240201 TI - Depression and anorexia nervosa of persons with Down syndrome. AB - The manifestations of major depression in three adults with Down syndrome, one of whom also suffered from anorexia nervosa, were described. The clinical manifestations depended on patient's developmental level, particularly on verbal language skills. Behavioral and vegetative symptoms predominated when the retardation was more severe, whereas in the higher functioning patient affective symptoms were more readily recognizable. The overall findings indicate that major depression in persons with Down syndrome may be more frequent than previously assumed and that it can be diagnosed with standard diagnostic DSM III criteria, modified according to the patient's developmental level. PMID- 6240203 TI - Serving profoundly mentally retarded persons: staff attitudes and job satisfaction. AB - Direct-care and professional staff members who served profoundly and multiply disabled persons in 13 small community settings or in a large specialty hospital generally expressed positive attitudes regarding their jobs and resident care. Further, staff members who worked with the most disabled residents did not differ from employees serving profoundly but relatively less impaired persons. Hospital direct-care staff, however, seemed to endorse more "normalized" interpersonal relationships with residents, even though the hospital might be considered a "more restrictive" setting. It therefore appears that normalization of the physical and interpersonal environments may be somewhat independent in facilities serving profoundly disabled persons. PMID- 6240204 TI - Facilitating visual discrimination learning of moderately and severely mentally retarded children through illumination of stimuli. AB - The effectiveness of illuminating the positive stimulus after a correct response in visual discrimination training of moderately and severely mentally retarded children was investigated. An economical unit for illumination of stimuli was designed for purposes of the present investigation and for possible use in nonspeech communication training of mentally retarded children. In Experiment 1, the illumination of black stimuli on white backgrounds failed to facilitate discrimination learning. In Experiment 2, however, illumination of white stimuli on black backgrounds facilitated discrimination learning. The findings in the second experiment support the use of changes in illumination as an attention influencing feature of nonspeech communication keyboards for retarded children. PMID- 6240205 TI - Immune complex disease complicating diabetic glomerulosclerosis. AB - We report immunopathologic findings observed in renal biopsies of 18 patients with diabetic glomerulosclerosis and associated glomerulonephritis. 10 patients had nodular and 8 patients diffuse diabetic glomerulosclerosis. Focal proliferative glomerulonephritis (4 patients), membranous glomerulonephritis (3 patients), postinfectious glomerulonephritis, Henoch-Schonlein nephritis, IgA nephropathy of Berger (1 patient each), and mesangiopathic glomerulonephritis (8 patients) were the superimposed conditions. In patients with diabetic renal disease, a rapid loss of renal function or an atypical urinalysis could be the expression of a superimposed immune complex disease. Because of functional and biochemical alterations, the glomeruli of diabetic patients may be more susceptible to immune-mediated injury. PMID- 6240207 TI - [Urinary plasmin in late pregnancy toxicosis]. PMID- 6240206 TI - Placental products induce suppressor cells of graft versus host reaction. AB - Cells from mice alloimmunized in the presence of placental extract were coinjected with cells from mice conventionally alloimmunized in the footpad of virgin female recipients. The contralateral footpad received a control twice the dose of cells from alloimmunized mice. Cells from the popliteal lymph nodes were harvested on day 3, and pulsed in vitro for measurement of proliferative capacity with 3H thymidine. The response of lymph nodes was compared (homo- vs contralateral). The cells from mice alloimmunized with placental extract in conjunction with alloantigens displayed a marked suppressive capacity of the local graft versus host (GVH) potential of cells from mice conventionally alloimmunized. It is suggested that this local GVH assay represents a quick, objective assay for suppressor-cell induction by placental products. PMID- 6240208 TI - [Dehydroepiandrosterone sulfate and serum immunoreactive estriol in biologically prolonged pregnancy]. PMID- 6240209 TI - [Bilateral pneumothorax following laparoscopy]. AB - A case of laparoscopy is presented with postoperative large subcutaneous emphysema and bilateral pneumothorax. As a result of careful control, conservative treatment, and consequent oxygen administration, this life threatening phenomena disappeared within a short time. Preventive measures for complications of diagnostic laparoscopy are discussed and established to lower the anaesthetic risk of this widely practised procedure. PMID- 6240210 TI - [Comparative study of atracurium and alcuronium for the intubation of older patients in halothane anesthesia]. AB - Intubation conditions, onset time (time from the end of the injection until the maximum twitch depression (1 Hz) of the adductor pollicis muscle) as well as changes in blood pressure and pulse rate were studied in a randomized double blind study of 40 male patients (average age 69-70 years) anaesthetized with halothane following atracurium (ATR) 0.33 mg X kg-1 or alcuronium (DAN) 0.1 mg X kg-1. An additional group received succinylcholine (SCH) 1.0 mg X kg-1. Intubation conditions at the end of the onset time were slightly and significantly better after ATR than following DAN, in each case, however, distinctly worse than after SCH. The onset time amounted to 115.0 s after ATR and 125.0 s following DAN (48.6 s after SCH). Neither ATR nor DAN showed statistically significant effects on blood pressure or pulse. One bronchospastic reaction which responded to therapy was observed per group. ATR proved to be comparable to DAN in respect to effectiveness and safety. PMID- 6240212 TI - [Evaluation of curarization]. PMID- 6240211 TI - Purification of the Neurospora crassa plasma membrane H+-ATPase by high-pressure liquid chromatography in the presence of sodium dodecyl sulfate. AB - Current methods for purifying the Mr 100,000 H+-ATPase from the plasma membrane of fungi and higher plants rely on detergent solubilization followed by density gradient centrifugation. The procedure yields catalytically active enzyme of high purity but takes several days, and the yields are low. For chemical studies on the primary structure of this enzyme, an alternative more rapid procedure was sought. In this paper a method which uses a high-performance gel filtration column in the presence of sodium dodecyl sulfate to purify nanomole quantities of the enzyme in only 30 min is described. With this procedure the enzyme was isolated free of other protein contaminants, as judged by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Gel filtration was performed on a high pressure liquid chromatograph equipped with a diode array spectrophotometric detector, allowing spectral analysis of the membrane proteins. An ultraviolet absorption spectrum of the plasma membrane Mr 104,000 H+-ATPase revealed an absorption peak at ca. 275 nm that is consistent with its content of aromatic amino acids. PMID- 6240213 TI - A pulsed phase measurement ultrasonic flowmeter for medical gases. AB - Pneumotachometers are used to measure instantaneous flowrate in the respiratory gas streams. The presently available devices suffer from lack of linearity, slow response times, and gas density sensitivity. A new design of an ultrasonic gas flowmeter is presented in this paper: We investigate the acoustic characteristics of ring and piston shaped transducers, and describe a sampling method to avoid the error due to reflection. A microcomputer is used to overcome the 360 degrees detection ambiguity problem associated with phase detection technique. This design has been tested in clinical settings and has been shown to give linear response, independent of gas density, and to have a wide dynamic range. PMID- 6240214 TI - Familial Richner-Hanhart syndrome: genetic, clinical, and metabolic studies. AB - The genetic, clinical, and metabolic studies of two familial cases of Richner Hanhart syndrome (type II hypertyrosinemia are described and the findings compared with other familial cases of palmo-plantar keratoderma. The clinical pictures are identical except that in the latter there are not ocular symptoms and the tyrosine levels are not raised. One of the two patients examined was treated with a diet low in tyrosine and phenylalanine with immediate improvement in clinical symptomatology and complete disappearance of the dendritic keratitis. PMID- 6240215 TI - [Cutaneous tuberculosis simulating acne conglobata: scrofuloderma]. PMID- 6240216 TI - Circulation, bone scans, and tetracycline labeling in microvascularized and vascular bundle implanted rib grafts. AB - The circulation in microvascularized rib grafts has been compared with that in conventional rib grafts and in those augmented by a direct vascular bundle implantation into the bone grafts. A new experimental model has been designed to correlate vascular perfusion, bone scan patterns, tetracycline labeling, and histological findings in these bone grafts. Posterior microvascularized rib grafts were found to have a circulatory pattern identical to that of the normal rib. Failed microvascularized rib grafts were revascularized more slowly than conventional rib grafts. Vascular bundles implanted into rib grafts remained patent and increased the rate of revascularization. The stripping or preservation of periosteum had no observable effects on the rate or pattern of conventional rib graft revascularization. The circulation in rib grafts was accurately reflected in technetium 99 bone scans, as was the patency of the anastomoses of microvascularized rib grafts and of implanted vascular bundles. In contrast, tetracycline labeling was repeatedly observed in avascular areas of bone grafts and, therefore, is not a reliable indicator of bone graft circulation. PMID- 6240217 TI - The vascular pattern and viability of microvascularized rib grafts based on periosteal circulation--an experimental study. AB - Previous reports have stressed the importance of the nutrient blood supply in rib grafts transferred by microvascular anastomoses. In the present experimental study, we have demonstrated that a rib graft transferred by microvascular anastomoses based on periosteal vessels can survive; vascular clearing studies demonstrated that the vascularity of these grafts extends not only into the cortex but the medulla as well. The relative facility of harvesting these grafts (compared with those based on nutrient vessels) should make them the favored choice. Technetium bone scintigraphy proved accurate in the assessment of both vascular pattern and microanastomotic patency. Tetracycline labeling did not correlate well with the patency of a rib graft's pedicle blood supply. PMID- 6240218 TI - [Angioplasty of arteries. Our experience in 450 cases]. PMID- 6240219 TI - [Percutaneous transluminal angioplasty. Preliminary experience apropos of 35 cases]. PMID- 6240220 TI - PTA in peripheral arteries. PMID- 6240221 TI - Immunological typing of acute lymphoblastic leukaemia patients in Singapore--a preliminary experience. AB - Six new patients with acute lymphoblastic leukaemia (ALL) have been studied with a battery of cell surface marker assays. These included T cell enumeration, B cell enumeration, monoclonal antibody studies for T cell subsets, (T helper cells, T suppressor cells and mature peripheral total T cells), HLA--DR (Ia-like antigens) and common ALL antigen. Three patients were found to have common ALL, 2 had null cell ALL and one had T cell ALL. Cytochemical studies on these 6 patients demonstrated a positive correlation between E rosette positivity and focal paranuclear staining with acid phosphatase. There appeared to be no correlation between FAB morphology and immunological subtype in the 6 patients studied. PMID- 6240222 TI - A subpopulation of lymph node B-CLL cells expresses the common acute lymphoblastic leukemia antigen. AB - Tumoral lymph nodes (LN) from 7 B-CLL patients were studied with a panel of monoclonal antibodies and in situ immunohistochemical technique. The large majority of LN B-CLL cells carried the phenotype slg+ BA-1+OKIal+ and was admixed with variable numbers of helper/inducer and suppressor/cytotoxic T-cells. In each of the LN studied, regularly distributed, scattered J5+TdT-BA-3- small lumphoid cells were observed, showing no topographical predilection, nor tendency to cluster. J5+ small lymphoid cells may represent pre-B cells which have entered the LN and proliferate and mature in situ, giving rise to a leukemic sIg+OKIal+BA 1+J5- population. This would explain the early generalized LN involvement in B CLL, and is in agreement with cell-kinetic and compartment in B-CLL LN. Alternatively, J5+ small lymphoid cells may represent a subset of LN B-CLL cells which have acquired the common acute lymphoblastic leukemia antigen during some transformation. PMID- 6240223 TI - Comparative trial of norfloxacin and trimethoprim-sulfamethoxazole in the treatment of women with localized, acute, symptomatic urinary tract infections and antimicrobial effect on periurethral and fecal microflora. AB - Forty-three women with acute, symptomatic urinary tract infections were randomized to receive either norfloxacin (400 mg) twice daily or trimethoprim sulfamethoxazole (160-800 mg) twice daily for 10 days. Of the 43 patients, 7 (16%) had low-count bacteriuria and pyuria and were included in the evaluation. Escherichia coli was isolated in 72% of the infections, whereas coagulase negative staphylococci were isolated in 14%. All isolates were susceptible to the assigned study drug. The MICs for 90% of the strains susceptible to norfloxacin and trimethoprim-sulfamethoxazole were less than or equal to 2 and less than or equal to 0.8-16 micrograms/ml, respectively. The cure rates for norfloxacin and trimethoprim-sulfamethoxazole were 95 and 90%, respectively. There were 17 patients with presumptive upper tract infections; only 1 of these relapsed after therapy. The effects on the periurethral flora were similar in both groups, but the infecting organism was eradicated from the fecal flora in 93% of the patients treated with norfloxacin and in 57% of the patients treated with trimethoprim sulfamethoxazole. More early reinfections occurred in the trimethoprim sulfamethoxazole group, with resistant organisms appearing in urine and in the periurethral and fecal flora in all cases. Three patients in each group experienced adverse clinical effects, but these were more severe in the trimethoprim-sulfamethoxazole group. No adverse hematological or biochemical changes were noted. From these results, we concluded that norfloxacin is at least as effective as trimethoprim-sulfamethoxazole in the therapy of acute, symptomatic urinary tract infections in women. PMID- 6240224 TI - In vitro activities of the spectinomycin analog U-63366 and four quinolone derivatives against Neisseria gonorrhoeae. AB - The in vitro activities of the new spectinomycin analog U-63366 and four new quinolone derivatives, rosoxacin, norfloxacin, ofloxacin, and ciprofloxacin, were compared with those of penicillin, tetracycline, thiamphenicol, cefotaxime, ceftriaxone, and spectinomycin against 222 beta-lactamase-negative and 25 beta lactamase-positive Neisseria gonorrhoeae strains. U-63366 was more active than spectinomycin, inhibiting 90% of the strains at a concentration of 2 mg/liter. Among the quinolone derivatives, ciprofloxacin was the most active compound in vitro (90% MIC, 0.002 mg/liter), followed by ofloxacin (90% MIC, 0.008 mg/liter), norfloxacin (90% MIC, 0.015 mg/liter), and rosoxacin (90% MIC, 0.03 mg/liter). PMID- 6240225 TI - Effect of mild heat treatment on the ATPase activity and proteolytic sensitivity of myosin subfragment-1. AB - The K+-EDTA-activated ATPase activity of chymotryptic myosin subfragment-1 (S-1) decreased by 85-90% when S-1 was incubated over a 2-h period at 35 degrees C. Addition of F-actin, ATP, or ATP analogs, such as ADP or PPi, to S-1 before incubation at 35 degrees C prevented the loss of ATPase activity. The decrease in ATPase activity was also accompanied by changes in tryptic sensitivity. Instead of the normal peptide pattern--which is comprised of three heavy chain fragments (27K, 50K, and 20K)--only two fragments (27K and 20K) appeared on the sodium dodecyl sulfate-gel electrophoregram after limited tryptic digestion of thermally treated S-1. Addition of any ligand--e.g. ATP, ADP, pyrophosphate, or actin- which prevented the loss of ATPase activity during incubation at 35 degrees C also prevented the observed change in the tryptic peptide pattern of S-1. Tryptic digested S-1, whose heavy chain has been cleaved to 27K, 50K, and 20K fragments, also lost its ATPase activity upon mild heat treatment. The heat-treated trypsin digested S-1 was subjected to a second tryptic digestion, which resulted in the disappearance of the 50K fragment, while the 50K fragment of tryptic S-1 not subjected to heat treatment was not susceptible to additional tryptic hydrolysis. The results indicate that the structural changes, that take place specifically in the 50K region of S-1 upon mild heat treatment, lead to both the loss of the ATPase activity and the changed tryptic sensitivity of S-1. PMID- 6240226 TI - Purification of the phosphofructokinase regulatory factors. AB - In this paper, the existence and purification of two species of phosphofructokinase regulatory factor activity are reported. The purification procedure included liver homogenization and ultracentrifugation, a 93 degrees C heat step on the supernate, precipitation with ammonium sulfate, DEAE-cellulose column chromatography, and Sephadex G-75 (fine) chromatography. Two discrete regions of factor activity were eluted from the DEAE-cellulose column with a 0 to 0.5 M linear NaCl gradient. The lesser anionic fraction was not significantly retarded by DEAE-cellulose at pH 7.6, and was referred to as factor A. The more anionic form, factor B, eluted at about 0.2 M NaCl. The presence of two active fractions was confirmed by separation of factor activity (prior to DEAE-cellulose chromatography) into two discrete species by preparative isoelectric focusing on granulated gel. The isoelectric points were approximately 7.0 for factor B and 8.5 for factor A. Factor A and factor B exhibited quite different elution volumes, i.e., apparent molecular weights, when applied to a Sephadex G-75 column. Rechromatography on a Sephadex G-75 column was used for further purification and estimation of native molecular weight. The gel filtration method yielded a molecular weight of 13,800 +/- 1,800 for factor A. Factor A activity eluted as a symmetrical protein peak of constant specific activity, suggesting a homogeneous preparation. For factor B, the absorption at 280 nm and activity profile did not directly overlap. When the peak absorbance at 280 nm was considered, a molecular weight range of 39,000 +/- 4,000 was found, and on the basis of activity the molecular weight range was 36,000 +/- 4,000. After the final Sephadex G-75 chromatographic step, sodium dodecyl sulfate (SDS) polyacrylamide slab gel electrophoresis of each SDS-treated factor preparation indicated that factor A, after visualization by silver staining, was homogeneous, with a subunit molecular weight of approximately 12,000. The factor B preparation consisted of two major polypeptides (11,000 and 18,000). The data appeared to support the conclusions that factor B was a dimer of the 18,000-Da subunit, and that the major contaminant was a tetramer of the 11,000-Da subunit. PMID- 6240227 TI - Properties of the phosphofructokinase regulatory factors. AB - The work presented herein describes many of the physiological properties of the phosphofructokinase regulatory factors. Factor activity can be separated into two discrete fractions, which were designated factor A and factor B, based on their respective charges. A preparation containing both factor A and factor B did not protect the following key carbohydrate-metabolizing enzymes from thermal inactivation: glucokinase, glucose-6-phosphatase (solubilized or nonsolubilized forms), pyruvate kinase, glucose-6-P dehydrogenase, muscle-type phosphofructokinase, or the minor liver phosphofructokinase isozyme. Factor activity in this sample was found to be Pronase sensitive, irreversibly precipitated by trichloroacetic acid, reversibly precipitated by adjusting the sample to a pH of 3.0, and stable to heating at 98 degrees C for 20 min. Distribution studies indicated that factor activity was found only in the soluble cell fraction and not in the mitochondrial or nuclear fractions. Factor activity was retained by 12,000-14,000 molecular weight cut-off (MWCO) dialysis tubing, and not retained by 50,000 MWCO dialysis tubing. These studies indicate that fructose-2,6-P2, calmodulin, or insulin-generated mediator are not associated with factor activity. Although fructose-2,6-P2 did not, both factor preparations protect the major liver phosphofructokinase isozyme (liver PFK) from inactivation by lysosomal extracts. In the diabetic rat, the activities of both factors are greatly reduced but return to near normal levels after 48 h of insulin administration. These data suggest that factor B had little or no effect on the kinetic properties of liver PFK. However, factor A was a K-type activator with respect to fructose-6-P, increasing both the Km and Ki for ATP, and slightly increasing the Vm. PMID- 6240229 TI - Phosphofructokinase from foot muscle of the whelk, Busycotypus canaliculatum: evidence for covalent modification of the enzyme during anaerobiosis. AB - Phosphofructokinase (PFK) was purified from foot muscle of aerobic and anaerobic (24 h of anoxia) whelks, Busycotypus canaliculatum. Fructose-6-P kinetics were sigmoidal at pH 7.0 with affinity constants, S0.5, of 2.18 +/- 0.10 (nH = 2.5 +/- 0.1) and 2.48 +/- 0.13 mM (nH = 2.7 +/- 0.1) for the enzyme from aerobic verus anaerobic muscle. Affinity for ATP, like that for fructose-6-P, did not differ for the two enzymes (0.031 +/- 0.003 for the aerobic vs 0.041 +/- 0.007 mM for the anaerobic enzyme), but S0.5 for Mg2+ was significantly different for the two enzymes (0.060 +/- 0.006 vs 0.130 +/- 0.020 mM). Whelk muscle PFK was activated by NH+4, Pi, AMP, ADP, and fructose-2,6-P2.NH+4 and fructose-2,6-P2 were less effective activators of PFK from anoxic muscle, with apparent Ka's 1.6- and 3.5 fold higher for the anaerobic vs aerobic enzyme. Activators decreased S0.5 for fructose-6-P and reduced nH. With the exception of fructose-2,6-P2, the effects of activators on S0.5 were the same for the enzyme from aerobic and anaerobic muscle; fructose-2,6-P2 at 2.5 microM reduced S0.5 by only 3.3-fold for the anaerobic enzyme compared to 5.5-fold for the aerobic enzyme. ATP was a strong substrate inhibitor of PFK; the enzyme from anaerobic muscle showed greater ATP inhibition, with I50's 1.5- to 2.0-fold lower than those for the aerobic enzyme. The kinetic differences between PFK from anaerobic versus aerobic foot muscle (stronger ATP inhibition and decreased sensitivity to activators for the anaerobic enzyme) were consistent with kinetic differences reported for the phosphorylated versus dephosphorylated forms, respectively, of PFK in other systems. Treatment of PFK from anaerobic muscle with alkaline phosphatase resulted in a decrease in the Ka for fructose-2,6-P2 to a level similar to that of the aerobic enzyme. The physiological stress of anoxia may, therefore, induce a covalent modification of PFK. PMID- 6240228 TI - The effect of deoxymannojirimycin on the processing of the influenza viral glycoproteins. AB - Deoxymannojirimycin (dMM) was tested as an inhibitor of the processing of the oligosaccharide portion of viral and cellular N-linked glycoproteins. The NWS strain of influenza virus was grown in MDCK cells in the presence of various amounts of dMM, and the glycoproteins were labeled by the addition of 2 [3H]mannose to the medium. At levels of 10 micrograms/ml dMM or higher, most of the viral glycopeptides became susceptible to digestion by endoglucosaminidase H, and the liberated oligosaccharide migrated mostly like a Hexose9GlcNAc on a calibrated column of Bio-Gel P-4. This oligosaccharide was characterized as a typical Man9GlcNAc by a variety of chemical and enzymatic procedures. Deoxymannojirimycin gave rise to similar oligosaccharide structures in the cellular glycoproteins. In both the viral and the cellular glycoproteins, this inhibitor caused a significant increase in the amount of [3H]mannose present in the glycoproteins. Deoxymannojirimycin did not inhibit the incorporation of [3H]leucine into protein in MDCK cells, nor did it affect the yield or infectivity of NWS virus particles. However, its effect on mannose incorporation into lipid-linked saccharides depended on the incubation time, the virus strain, and the cell line. Thus, high concentrations of dMM showed some inhibition of mannose incorporation into lipid-linked oligosaccharides with the NWS strain in a 3-h incubation, but no inhibition was observed after 48 h of incubation. On the other hand, the PR8 strain was much more sensitive to dMM inhibition, and mannose incorporation into lipid-linked oligosaccharides was strongly inhibited when the virus was raised in chick embryo cells, but less inhibition was observed when this virus was grown in MDCK cells. Nevertheless, in these cases also, the major oligosaccharide structure in the glycoproteins was the Man9GlcNAc2 species. PMID- 6240231 TI - [Social injustice in relation to illness and death]. PMID- 6240230 TI - Studies on the role of polymorphonuclear leukocyte granule elastase in Arthus reaction. AB - In the present study, attempts were made to clarify the role of an elastase-like enzyme in Arthus reaction by using rabbit-peritoneal polymorphonuclear leukocytes (PMNs). It was first confirmed that the injection of large amounts of PMNs with antibody can increase tissue damage in reversed Arthus reaction. The five various fractions, which were intact PMNs, whole homogenate, granule fraction, nuclei and cell debris, and membrane extract, were prepared from rabbit-peritoneal exudate. Each fraction was intracutaneously injected into the abdominal wall of rabbit. It was of particular interest that the tissue damage induced by membrane extract occurred earlier and was more severe than that caused by the others. Furthermore, membrane extract possessed remarkably higher caseinolytic and elastinolytic activities than the others. The membrane extract was partially purified by Sephadex G-100 column chromatography. The protein concentration of the elastase like enzyme solution was 3.64 mg/ml, and its specific activity was 195 caseinolytic units and 0.45 elastinolytic units per milligram of protein. The cutaneous reaction by membrane extract was dependent on the concentration of this elastase-like enzyme and could be strongly inhibited by Elastatinal. From these results, the authors suggest that an elastase-like enzyme which originates in PMN granules is the key enzyme that promotes the severity of tissue damage in Arthus reaction. PMID- 6240232 TI - [Echocardiography in the evaluation and pre- and postoperative follow-up of chronic aortic insufficiency]. AB - In chronic aortic regurgitation (CAoR) is difficult to determine the moment in which volume overload produces the myocardial deterioration which originates symptoms. We pretend to demonstrate the utility of echocardiography in defining the correct timing of operative correction in CAoR with pre- and post-operative comparison. Thirteen patients with CAoR (systolic ventricular-aortic gradient less than 20 mmHg) in whom the aortic valve was replaced were studied with an average of 13.7 months of follow-up. Two patients died immediately after surgery. Those remaining had a decrease in cardiomegaly grade and moved into functional class I. The echocardiogram revealed a significant reduction (P less than 0.01) in diameters of the left ventricle. The ejection fraction increased (P less than 0.05) in the post-operative period. Fractional shortening (FS) and mean velocity of circumferential shortening showed no significant change. The index end systolic diameter over normalized velocity of the posterior wall IESD/NVPW) decreased considerably and the mean velocity of circumferential relaxation (Vcfr) increased (P less than 0.001) after surgical treatment. The preoperative ESD/NVPW index and Vcfr correlated well with the left ventricular end-diastolic pressure (r = 0.891 and r = -0.885, respectively). There was no difference in the course of those patients with diminished FS. The ESD/NVPW index and the Vcfr allowed a better evaluation of the residual volume, of the Frank-Starling law and of distensibility as an expression of the ventricular function. Consequently we conclude these indices are useful to establish the best moment for pre-operative catheterization in patients with CAoR. PMID- 6240233 TI - [Cardiovascular manifestations in mixed connective tissue disease in adults]. AB - Twenty two patients with mixed connective tissue disease (MCTD) were studied with noninvasive cardiovascular techniques. Fifty percent of the cases presented cardiovascular abnormalities which in order of importance were: pericarditis with effusion (28%), myocarditis (14%) and one case; myocardial infarction. Complications of less importance were: supraventricular and ventricular premature beats, enlargement of left and right cardiac chambers, septal hypertrophy and type A paradoxical septal movement. We consider that patients with MCTD should have a routine cardiological evaluation. PMID- 6240234 TI - [Beneficial effects of coronary transluminal angioplasty on resting left ventricular systolic function]. AB - Resting left ventricular systolic function was studied by cardiac catheterisation before and 6 months after effective transluminal coronary angioplasty (TCA) to evaluate the myocardial effects of this procedure. The global left ventricular systolic function was assessed by measuring ventricular volumes, the ejection fraction, the mean velocity of circumferential fibre shortening (m VCF) and mean normalised systolic ejection rate (MNSER). The regional function was studied by dividing the left ventricle into 8 regions using the Stanford radial model and measuring the percentage shortening and velocity of circumferential fibre shortening (VCF). These parameters were obtained from selective left ventriculography filmed at 100 frames/second in the RAD plane. Left ventricular function was analysed from the whole of systolic ejection and then sequentially during each third of systole (early-mid-and end systole). The 10 patients studied had an average age of 45 years. Coronary angiography was performed for unstable angina (6 cases), stable angina (3 cases) and post-infarction angina (1 case). Except for 1 patient with associated LAD and right coronary disease they all had single vessel disease. TCA was performed on the LAD artery in 8 cases, on a dominant left circumflex artery in 1 case and on a right coronary artery in 1 case. The efficacy was demonstrated by angiographic reduction of the degree of stenosis (85 to 25 p. 100 immediately after TCA, and 30 p. 100 at control angiography at 6 months), and by a reduction of more than 40 p. 100 in the average transstenotic pressure gradient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 6240235 TI - [Cost of a coronary transluminal angioplasty compared with a single coronary bypass. Economic effects]. AB - The authors discuss the financial incidence of transluminal coronary angioplasty (TCA) compared to isolated coronary bypass surgery (CBS). The study was limited to 1982 (76 cases of TCA) and compares two groups: successful TCA (17 consecutive cases: group I); isolated CBS (18 cases: group II). The following parameters were studied in each group: average length of hospital study, credits received from the Department of Social Security, hospital expenditure. Hospital expenditure was classified under 6 headings: personnel, material, investigations, drugs, hospital costs and administration costs. The results expressed as the mean per patient were: in group I: hospital stay, 10 days; Social Security reimbursement, 10 813 FF; hospital expenditure, 10 586 FF. In group II: hospital stay, 18 days (including 4 days in the ICU); Social Security reimbursement 46 656 FF; hospital expenditure, 28 955 FF. The hospital costs of personnel were relatively small (especially for TCA). The economies realised by reutilising catheters designed for single usage were significant: the use of guide wires, catheters and balloon catheters falls from 1.64, 1.9 and 0.1 per patient to 0.47, 0.53 and 0.05 respectively, a saving of 5 068 FF per TCA and 385 168 FF per year. Compared to costs in the United States (4 773 and 14 952 dollars) TCA and CBS is much cheaper in France.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 6240236 TI - [Wolff-Parkinson-White syndrome and cardiopathies]. AB - Forty-nine cases of Wolff-Parkinson-White syndrome (WPW) were diagnosed out of 10 750 patients with cardiac disease (0.45 p. 100), 24 cases out of 3 761 congenital malformations and 25 cases in the 6 989 patients with acquired heart disease. Right ventricular pre-excitation was recorded in 31 cases; 13 in the lateral zone, 12 in the posterior paraseptal zone and 6 in the anterior paraseptal zone. Left ventricular pre-excitation was recorded in 18 cases: 8 in the lateral zone, 5 in the anterior paraseptal and 5 in the posterior paraseptal zones. WPW and congenital heart disease: Out of 20 cases of Ebstein's anomaly, 5 cases of WPW were observed: 4 right posterior and 1 right lateral pre-excitations. Out of 218 cases of hypertrophic obstructive cardiomyopathy, 7 cases of WPW were observed, 4 of which were congenital. Three cases of WPW were recorded in 699 patients with ventricular septal defects. Out of 1 348 cases of atrial septal defect, 5 cases of pre-excitation were recorded, including 3 right posterior pre-excitations associated with an ostium primum defect. Pre-excitation was also observed in isolated cases of corrected transposition of the great arteries, supravalvular aortic stenosis, aortic incompetence and patent ductus arteriosus. Pre-excitation and acquired heart disease: Five cases of pre-excitation were recorded out of 305 cases of dilated cardiomyopathy (1.62 p. 100). Eleven cases of pre-excitation were recorded in a total of 3 471 cases of valvular heart disease (0.31 p. 100): 9 in rheumatic valve disease and 2 in mitral valve prolapse. Nine cases of pre excitation were observed in 2 850 cases of coronary artery disease. Intermittent Wolff-Parkinson-White syndrome: Ventricular pre-excitation masks the ECG changes of complete right bundle branch block in Ebstein's anomaly, complete left bundle branch block in aortic incompetence and dilated cardiomyopathy, and the in complete right bundle branch block often seen in mitral valve prolapse. The characteristic appearances of WPW depend on the zone of pre-excitation. Right ventricular hypertrophy observed in ventricular septal defect with pulmonary stenosis and mitral stenosis may be masked by right lateral pre-excitation. Changes of inferior wall myocardial infarction may be masked by left anterior wall pre-excitation. On the other hand, the effects of WPW on left ventricular hypertrophy are variable, high amplitudes of the resultant forces seeming to depend on late and isolated activation of one of the left ventricular walls. PMID- 6240237 TI - [M-mode and two-dimensional echocardiography of 7 cases of cardiac amyloidosis]. AB - Although rare, cardiac amyloidosis is the commonest cause of infiltrative myocardiopathy. The diagnosis may be suspected clinically in patients with mainly right ventricular failure of sudden onset. The aim of this study was to assess the diagnostic value of M-Mode and 2D echocardiography in this condition. Seven cases of cardiac amyloidosis were studied. Biventricular hypertrophy, usually more severe on the left side with reduction in size of the left ventricular chamber, was observed in all cases. Parameters of systolic and diastolic function were abnormal. A significant pericardial effusion was demonstrated in 3 patients. 2D echocardiography also allows evaluation of the myocardial structure: in 3 cases the whole of the left ventricular myocardium seemed granular, sparkling and abnormally echogenic. In patients with cardiac failure these appearances are very suggestive of amyloidosis, especially when the ECG shows low voltage complexes and pathological Q waves. In 3 other patients, this abnormal echogenic myocardial appearance was observed only in the interventricular septum, which is much less suggestive of cardiac amyloidosis. In conclusion, in patients with cardiac failure with cardiomegaly and a low voltage ECG, echocardiographic findings of hypertrophic cardiomyopathy (only rarely with dilatation) and hypokinetic wall motion are suggestive of cardiac amyloidosis, especially when the myocardium has a granular, sparkling appearance. PMID- 6240238 TI - [Pulsus alternans: alternation of relaxation parameters]. AB - Pulsus alternans was observed during transluminal coronary angioplasty of the left anterior descending artery in a 48 year old man. Analysis of left ventricular pressures (Millar catheter) showed alternation of the parameters of relaxation. After the strong beats there was a lengthening of the relaxation constant T (78.8 +/- 3.9 ms compared to 72.9 +/- 4.4 ms, p less than 0.001), a widening of the negative deflection of dp/dt without a significant variation in amplitude and the point of minimal diastolic pressure was delayed. The first weak beat occurred after the longest constant of relaxation T and the lowest negative deflection of dp/dt. Regression of pulsus alternans was accompanied by a progressive decrease of T and an increase in amplitude and narrowing of the negative deflection of dp/dt. The increase in the constant of relaxation T and widening of the negative dp/dt, more apparent after the weak beats, could be signs of left ventricular asynchronism. PMID- 6240239 TI - Chitosomes from the wall-less "slime" mutant of Neurospora crassa. AB - Cell-free extracts from the wall-less slime mutant of Neurospora crassa and the mycelium of wild type exhibit similar chitin synthetase properties in specific activity, zymogenicity and a preferential intracellular localization of chitosomes. The yield of chitosomal chitin synthetase from slime cells was essentially the same irrespective of cell breakage procedure (osmotic lysis or ballistic disruption)--an indication that chitosomes are not fragments of larger membranes produced by harsh (ballistic) disruption procedures. The plasma membrane fraction, isolated from slime cells treated with concanavalin A, contained only a minute portion of the total chitin synthetase of the fungus. Most of the activity was in the cytoplasmic fraction; isopycnic sedimentation of this fraction on a sucrose gradient yielded a sharp band of chitosomes with a buoyant density = 1.125 g/cm3. Approximately 76% of the total chitin synthetase activity of the slime mutant was recovered in the chitosome band. Because of their low density, chitosomes could be cleanly separated from the rest of the membranous organelles of the fungus. Apparently, the lack of a cell wall in the slime mutant is not due to the absence of either chitosomes or zymogenic chitin synthetase. PMID- 6240240 TI - Sex-dimorphic behavior in childhood subsequent to prenatal exposure to exogenous progestogens and estrogens. AB - Thirteen boys and 15 girls with a history of prenatal exposure to medroxyprogesterone acetate only and 22 boys and 15 girls with exposure to a variety of progestogens and estrogens singly or in combination were studied at age 8-14 years in comparison to closely pair-matched, unexposed controls. This report concerns the findings on sex-dimorphic behavior as assessed by separate interviews with the child and his/her mother. Hormone-exposed boys and controls differed little, while in girls prenatal sex hormone treatment seemed to be associated with some degree of increased stereotypic femininity. PMID- 6240241 TI - Effects of prenatal hormone exposure versus pregnancy complications on sex dimorphic behavior. AB - The existing literature on human subjects indicates demasculinization as an effect of prenatal exposure to various exogenous sex hormones, except for 19-nor progestogens. For the samples described in Ehrhardt et al. (1984), the current study examines whether the demasculinization can be explained by pregnancy complications. Corresponding covariates were constructed. In order to permit parametric analysis, the primary rating scales used previously were factor analyzed and aggregated to form cluster scales where feasible. The factor analysis also demonstrated the existence of a general factor of sex-dimorphic behavior. Subsequent case-control comparisons by t test and by analysis of covariance for the general-factor and cluster scales showed that pregnancy complications do not explain the modest demasculinization effects of prenatal hormone exposure observed in females. A few paradoxical results emerged in males, likely to be due to chance. PMID- 6240242 TI - Multiple actions of steroids and their antagonists. AB - Our scientific language is often misleading. We speak, for example, of virilizing progestins when we should be speaking of "dihydrotestosterone-like" progestins because genital virilization is normally brought about by DHT. We speak of the anti-libidinal properties of antiandrogens as though we knew that their mechanism of action was through the blockage of androgen receptors; some of these agents are antiestrogenic and progestational as well. Until we know the mechanism of action of androgens, estrogens, antiandrogens, antiestrogens, aromatase inhibitors, and reductase inhibitors we should be cautious in our terminology. All hormones and their antagonists have multiple effects. PMID- 6240244 TI - Cardiac hypertrophy in the dog and rat induced by oxfenicine, an agent which modifies muscle metabolism. AB - Oxfenicine (S-4-hydroxyphenyl glycine) has been shown to protect the rat and dog heart from experimentally induced myocardial ischaemia probably as a result of its ability to divert myocardial metabolism from fatty acid to carbohydrate utilization with a consequent reduction in oxygen consumption. When various dose levels of oxfenicine were administered to dogs for periods of up to 1 year and rats for periods of up to 2 years, dose-related increases in cardiac weight were observed. No increases in cardiac weight were observed in the rat after only 3 months of treatment but increases were observed in the dogs after a similar treatment period. Macroscopic, light, histochemical and electron microscopic examination of the myocardium revealed that the increase in heart weight was due to uniform myocardial fibre hypertrophy involving all cardiac chambers. Individual muscle fibres were increased in size but there was no clear disproportion of mitochondria and myofibrils. Although intracellular lipid was increased, vacuolated lysosomal structures were only occasionally observed. No histochemical differences in lysosomal enzyme activity were observed between the treated and the control rats. The structural changes were fully compatible with myocardial hypertrophy due to the decreased energy forming capacity of heart muscle resulting from inhibition of fatty acid oxidation by oxfenicine. PMID- 6240243 TI - Nature of N-nitrosodimethylamine demethylase in hepatic microsomes of rats. AB - The nature of enzymes involved in demethylation of N-nitrosodimethylamine (NDMA) was investigated in hepatic microsomes of rats. Compared to the other cytochrome P-450-dependent enzymes. NDMA demethylase had anomalous properties as reported in the literature. However, kinetic analysis suggested a qualitative change in NDMA demethylase induced by phenobarbital (PB) and 3-methylcholanthrene (MC) pretreatment. The inhibition of demethylase by alpha-naphthoflavone in MC-treated microsomes also suggested that cytochrome P-450 species induced by MC are active in demethylating NDMA. The enhancement of NDMA demethylase activity by metyrapone in PB-treated microsomes was greater than in non-treated ones, and was not observed in MC-treated ones. The result is almost the same as in acetanilide hydroxylation, depending on cytochrome P-450. Pyrazole, tranylcypromine, and aminoacetonitrile, which are selective inhibitors of NDMA demethylation, interacted with cytochrome P-450 species to produce type-II spectra, and typical type-II compounds (aniline, imidazole, and nicotinamide) were inhibitors of the NDMA demethylation. Tranylcypromine irreversibly inhibited microsomal monoamine oxidase [EC 1.4.3.4], but not NDMA demethylase. Semicarbazide (a copper- and pyridoxal-containing amine oxidase [EC 1.4.3.6] inhibitor) had no effect on demethylation. From these results it is concluded that NDMA demethylation depends only on cytochrome P-450-dependent monooxygenases. PMID- 6240245 TI - [Surgical experience with patients undergoing coronary angioplasty]. PMID- 6240246 TI - [A new model of the pivoting disc prosthesis: initial experiences]. PMID- 6240247 TI - Preparing the pediatric patient for urological X-rays. PMID- 6240248 TI - Play therapy for the hospitalized child. PMID- 6240249 TI - Hematuria revisited. PMID- 6240251 TI - Hypospadias and postoperative nursing care. PMID- 6240250 TI - Utilization of a new flexible catheter guide system. PMID- 6240252 TI - Ly 2 positive cytotoxic T lymphocytes, whether specific or non-specific in lytic activity, may express a large, granular, vacuolated lymphocyte morphology. AB - Cytotoxic clones consisting entirely of large, vacuolated granular lymphocytes (LGL) are produced with high frequency when individual purified mature Ly 2+ T cells are cultured at limit dilution in the presence of concanavalin A and irradiated spleen filler cells. Similar cells are produced in cultures of Ly 2- T cells but in lower proportion, the level of granular lymphocytes amongst the largely non-cytotoxic, Ly 2- L3T4+ product cells being only 20%. A proportion (15%) of LGL are also found in conventional mixed lymphocyte cultures. In the limit-dilution cultures of Ly 2+ T cells the LGL originate from the single precursor cell and not from the irradiated filler cells. They bear the markers expected of active cytotoxic T lymphocytes (Thy 1++; PNA++; Ly 1+; Ly 2++; L3T4 ). Their DNA and chromosome complement appear normal. The granules within the cells are heterogeneous in form, and some resemble in ultrastructure those described in certain cytotoxic, suppressor and NK-cell lines. The granules do not show mast cell staining characteristics. The LGL are not phagocytic. Although LGL are associated with nonspecific cytotoxicity late in culture, the first granular cells appear early (day 3) and dominate in the clones at times when cytolysis is specific. LGL appear to be the normal morphological form of cytotoxic T lymphocytes when grown under these conditions. PMID- 6240253 TI - Autoantibody-specific suppressor cells are elicited by membrane components of rat RBC independently of circulating autoantibodies but TNP-specific suppressors are not elicited by TNP-rat RBC. AB - Erythrocyte autoantibodies and autoantibody-specific suppressor cells are elicited in mice injected with rat erythrocytes. Here it is shown, first, that modified rat erythrocytes elicit suppressor cells independently of autoantibody production. Haemoglobin-free membranes of rat erythrocytes, but not soluble lysates of rat erythrocytes, elicited autoantibodies and suppressor cells. Solubilization of these rat erythrocyte membranes with solutions of Triton-X-114 produced membrane fractions which induced autoantibody-specific suppression in the absence of detectable autoantibody production. These results are compatible with the view that the activation of suppressor cells in this model involves recognition of structures on the rat erythrocytes. Secondly, trinitrophenyl (TNP) was attached to rat erythrocytes in various doses in attempts to make the immunogenicity of TNP similar to that of the cross-reactive determinants on rat and mouse erythrocytes, to determine whether TNP-specific suppressor cells were produced. The results show that at various doses of TNP, including those at which antibody production to TNP could not be detected, rat erythrocytes coated with TNP induced autoantibody-specific suppressor cells but not suppressor cells with specificity for antibodies to TNP. PMID- 6240255 TI - Nurse & the Law. Most heinous of crimes. Part III. PMID- 6240254 TI - Promoting effect of beer and ethanol on anti-tumour cytotoxicity: unaffected growth of a transplantable rat tumour. AB - The effects of beer and alcohol (4.8% ethanol v/v) were studied on (i) the growth of a syngeneic colonic carcinoma transplantable in male D/A rats, (ii) levels of blood B and T-lymphocyte classes, (iii) antibody-dependent cellular cytotoxicity (ADCC), and (iv) direct lymphocyte anti-tumour cytotoxicity. Beer and alcohol had no effect on tumour growth, but led to significant increases in non-specific anti tumour cytotoxicity in the levels of blood lymphocytes labelled by the monoclonal antibody OX/8 (cytotoxic/suppressor cells) and in the levels of total T lymphocytes; ADCC was not affected. It is concluded that alcohol stimulates non specific cell-mediated immunity (CMI) but that it either does not affect tumour growth or that the increased CMI is compensatory for a tumour-growth stimulatory effect of alcohol. PMID- 6240256 TI - The velocity of sound in human blood. PMID- 6240257 TI - Balloon angioplasty of a superior mesenteric artery occlusion in a patient with angiodysplasia of the caecum. PMID- 6240258 TI - Lymphocyte subclasses in pregnancy induced hypertension. AB - Peripheral blood lymphocyte subclasses were studied by flow cytofluorimetry and monoclonal antibodies in 21 women with Pregnancy Induced Hypertension (PIH), 20 healthy women in their third trimester of pregnancy and in 20 nulliparous, nonpregnant women. The cells were stained with the monoclonal antibodies OKT3, OKT4 and OKT8 to define total T cells, T helper cells (Th) and T suppressor cytotoxic cells (Ts/c) respectively. B lymphocytes were defined by their surface immunoglobulin. Absolute numbers of total T cells and Ts/c cells were significantly decreased (p less than 0.05) in patients with PIH compared to either control group. The proportion of B lymphocytes was significantly (p less than 0.01) increased and absolute numbers were marginally increased. These findings reflect an immune disturbance which may be of prime importance in the pathogenesis of this disease. PMID- 6240259 TI - [Lungworms in sheep in Hesse: incidence of Dictyocaulus filaria and protostrongylids as well as seasonal dynamics of larval excretion under various management systems]. PMID- 6240261 TI - Localization of the complement-component-C3b-binding site and the cofactor activity for factor I in the 38kDa tryptic fragment of factor H. AB - Trypsin treatment of human factor H (H160) [enzyme/substrate ratio 1:100 (w/w), 30 min, 37 degrees C] generated a 38 kDa (H38) and a 142 kDa (H142) fragment linked by disulphide bonds (H38/142). The fragments were purified by reduction with 2-mercapto-ethanol, gel filtration on a Sephadex G-200 column and affinity chromatography with monoclonal anti-(factor H) antibody coupled to Sepharose 4B. This monoclonal antibody bound to a site in the 38 kDa fragment. To localize the C3b binding site in factor H we used two enzyme-linked immunosorbent assays (e.l.i.s.a.). For the first test, e.l.i.s.a. plates were coated with C3b; H160, H38/142, H38 and H142 were added, and their binding was monitored by goat anti (factor H) and peroxidase-labelled rabbit anti-goat antibodies. Only intact factor H bound to the C3b-coated plates. For the second test, e.l.i.s.a. plates were coated with comparable amounts of factor H or its fragments, and C3b was offered at several dilutions. In contrast with the results from the first assay, C3b bound to intact factor H, H38/142 and H38 but not to H142, thus characterizing H38 as the fragment carrying the C3b-binding site. To identify the fragment responsible for the cofactor activity of factor H (cleavage of fluid phase C3b by factor I), 125I-C3b was incubated with either H38 or H142 and factor I. H142 had no cofactor activity, whereas H38 had the same cofactor function as intact H. To further investigate the relationship between the C3b-binding site and the site of factor H essential for its cofactor activity, we made use of monoclonal antibodies directed against the H38. Those antibodies inhibiting the binding of C3b to H160 also inhibited the cofactor function, whereas those without effect on the C3b binding also did not interfere with the cofactor activity. This suggests that the C3b-binding site and the site essential for the cofactor activity of factor H are both localized in the 38 kDa tryptic fragment of factor H in close proximity or are identical. PMID- 6240260 TI - Differences in tissue expressions of enzyme activities in interspecific sunfish (Centrarchidae) hybrids and their backcross progeny. AB - The extent of naturally occurring variations of enzyme locus expression was determined for three tissues (liver, muscle, and eye) in two species of sunfish (Centrarchidae), the green sunfish (Lepomis cyanellus) and the redear sunfish (L. microlophus). The genetic basis for species differences in tissue enzyme specific activities of malate dehydrogenase (EC 1.1.1.37), lactate dehydrogenase (EC 1.1.1.27), phosphoglucomutase (EC 2.7.5.1), and glucosephosphate isomerase (EC 5.3.1.9) was investigated by determining enzyme specific activities in the tissues of the reciprocal F1 hybrids and of their backcross progenies. The specific activities for most enzymes in hybrids were intermediate between those of the parental species. Significant differences in enzyme specific activity were detected among the F1 progeny as well as those of backcrosses. Variations in specific activity levels in one tissue were often independent of variations in specific activities in a different tissue. However, the changes in the specific activities of different enzymes within the same tissue were often positively correlated. The tissue glucosephosphate isomerase activity differences appear not to be due to different functional contributions of the glucosephosphate isomerase allelic isozymes. Cluster analysis of distributions of specific activities revealed no simple Mendelian pattern of inheritance for control of tissue enzyme activity. Our results suggest a polygenic control of tissue enzyme specific activity levels. PMID- 6240262 TI - Quantification of liver and kidney phosphofructokinase by radioimmunoassay in fed, starved and alloxan-diabetic rats. AB - A newly developed specific radioimmunoassay was used to quantify phosphofructokinase protein directly and independently of assayable activity in liver and kidney cytosol of normal fed, starved and alloxan-diabetic rats. In the fed state, liver phosphofructokinase concentration was 0.096 microM and the kidney enzyme was 0.086 microM (mumol/kg of tissue). In the starved state (24h), liver and kidney phosphofructokinase concentrations decreased by 30%. Prolonged starvation up to 72h did not further decrease enzyme concentration. In liver, total enzyme content during starvation declined by more than 50%, secondary also to a decrease in liver weight. In the alloxan-diabetic rats, there was a 22% decrease in enzyme protein concentration in liver and kidney. Total enzyme content per liver actually decreased much more (46%), because diabetes also resulted in a decrease in liver size. In conjunction with assayable activity measurements, the results of the radioimmunoassay allowed us to calculate the apparent specific activity of the enzyme. The specific activity of the kidney enzyme was 2-3 times that of the liver. Little or no change in specific activity of the liver or kidney enzyme occurred as a result of starvation or chemically induced diabetes. Tissue enzyme concentrations of phosphofructokinase unequivocally reconcile the ultimate results of changing rates of synthesis and degradation and are useful data in the design of spectrophotometric, kinetic, aggregation-disaggregation and other studies. PMID- 6240263 TI - Interaction with protein SH groups could be involved in adriamycin cardiotoxicity. AB - The use of the antineoplastic agent adriamycin is limited by its cardiotoxicity. The mechanism of cardiotoxicity has been investigated through the study of adriamycin effects on a number of heart enzymes. Adriamycin inhibited the activity of NADP-isocitrate dehydrogenase, malic enzyme, and 6-phosphogluconate dehydrogenase, three enzymes that have in common the presence of reactive SH groups involved in activity. Adriamycin action was prevented by the presence of proteins or dithioerythrol and mimicked by dithiobis dinitrobenzoate. It is suggested that adriamycin effects are due to interaction with enzyme SH groups by a product of adriamycin metabolism. PMID- 6240264 TI - [Sulfated macromolecules in connective tissue and their metabolism]. AB - Sulfated macromolecules are one of the major constituents of the extracellular matrix of connective tissue. The degree of sulfation is responsible for the physico-chemical properties of the extracellular matrix. Especially the fixed charged groups contribute to the reversible compressibility of the cartilage. The sulfation may play also a role in the regulation of metabolic pathways. The derivatives of sulfate are formed by the help of specific sulfotransferases, transferring the "active" sulfate group from PAPS to the macromolecules. Too low an activity of certain sulfotransferases is responsible for some types of spondyloepiphyseal dysplasia, and too low a concentration of PAPS leads to dwarfism. The sulfate groups of the macromolecules are degraded by specific sulfatases. A genetically caused deficiency in one of these enzymes (mucopolysaccharidoses) is frequently associated with skeletal deformities. The amount and composition of proteoglycans is altered in the ontogenesis. Similar alterations are associated with ageing and arthrotic processes, being difficult to differentiate. The characterization of the alterations in degenerative joint diseases, especially, is important for ethiopathogenetic studies. The most widely used methods for the determination of sulfated macromolecules and particularly analytical parameters of the sulfate metabolism are described. PMID- 6240266 TI - Plasmin cleaves human beta-casein. AB - Plasmin cleaves isolated human beta-casein to form specific fragments in a manner similar to the generation of gamma 1-, gamma 2-, and gamma 3-caseins from the bovine homologue. Identification of a protein previously isolated from human milk as a specific plasmin cleaved portion of beta-casein indicates that endogenous plasmin is active in whole milk. These findings suggest that protease activity should be considered in casein quantitation or isolation of components from human milk. PMID- 6240265 TI - Fetal calf serum and epidermal growth factor prevent the inhibitory action of a chalone-like growth inhibitor for Ehrlich ascites mammary carcinoma cells in vitro. AB - A growth inhibitor for the Ehrlich ascites mammary carcinoma, purified from bovine mammary gland, is antagonized by very low concentrations of epidermal growth factor (2-16 X 10(-10) M) or fetal calf serum (0.001-0.1%). Thus, epidermal growth factor and the compounds in fetal calf serum have the same effect as earlier described for insulin and proinsulin [1-3]. PMID- 6240267 TI - Adrenocortical cytochrome P-450 responsible for cholesterol side chain cleavage (P-450scc) is phosphorylated by the calcium-activated, phospholipid-sensitive protein kinase (protein kinase C). AB - Purified bovine adrenocortical cytochrome P-450scc (specific for cholesterol side chain cleavage in the inner mitochondrial membrane) was selectively phosphorylated in vitro by a Ca2+-activated, phospholipid-sensitive protein kinase (protein kinase C) preparation, whereas cyclic AMP dependent and two cyclic nucleotide independent kinases were ineffective. Cytochrome P-450scc incorporated a maximum of 4 mol of phosphate in the presence of protein kinase C within 15 min at 30 degrees C, with apparent Km and Vmax of 0.14 mumol and 0.76 pmol/min, respectively. Serine and threonine were the two target aminoacids phosphorylated in a ratio of about 1:1. In the presence of 1 microM Ca2+, a mixture of phosphatidylserine and diolein (or a potent tumor promoter phorbol ester) was required for optimal cytochrome P-450scc phosphorylation. In addition, purified inner mitochondrial membrane preparations from adrenocortical mitochondria were found to contain protein kinase C activity. These findings, together with the previous demonstration that activators of protein kinase C such as a potent phorbol ester activates steroidogenesis of intact adrenocortical cells, suggest that phosphorylation of P-450scc should be examined for its possible role in the regulation of adrenocortical functions. PMID- 6240268 TI - Docosahexaenoic acid (22:6, n-3) is metabolized to lipoxygenase reaction products in the retina. AB - Docosahexaenoic acid (22:6, n-3), a major component of retinal phospholipids, is a substrate for active lipoxygenation in intact canine retinas incubated in vitro with [U-14C]docosahexaenoic acid. The major lipoxygenase reaction product was identified by high performance liquid chromatography and gas chromatography-mass spectrometry as 11-hydroxy-4,7,9-(trans)13,16,19 docosahexaenoic acid. Other mono and di-hydroxy derivatives also were detected. The synthesis of these compounds was inhibited by the antioxidant and lipoxygenase inhibitor, nordihydroguaiaretic acid, but was not inhibited by indomethacin or esculetin. PMID- 6240269 TI - NAD (P) H-dependent reduction of nicotinamide N-oxide by an unique enzyme system consisting of liver microsomal NADPH-cytochrome C reductase and cytosolic aldehyde oxidase. AB - NAD (P) H-dependent reduction of nicotinamide N-oxide was investigated with rabbit liver preparations. Microsomes, microsomal NADPH-cytochrome c reductase or cytosolic aldehyde oxidase alone exhibited no nicotinamide N-oxide reductase activity in the presence of NADPH or NADH. However, when the microsomal preparations were combined with the cytosolic enzyme, a significant N-oxide reductase activity was observed in the presence of the reduced pyridine nucleotide. The activity was enhanced by FAD or methyl viologen. Cytosol alone supplemented with NADPH or NADH exhibited only a slight, but when combined with microsomes, a significant N-oxide reductase activity. Based on these facts, we propose a new electron transfer system consisting of NADPH-cytochrome c reductase and aldehyde oxidase, which exhibits nicotinamide N-oxide reductase activity in the presence of the reduced pyridine nucleotide. PMID- 6240270 TI - The effect of benzyl beta-D-xyloside on keratan sulphate synthesis in ox articular cartilage. AB - Cartilage from adult bovine hock joints was incubated with [3H]galactose or [35S]sulphate in the presence of benzyl beta-D-xyloside. Radioisotope incorporation into proteoglycan was inhibited by the xyloside; the magnitude of this inhibition depended on the concentration of xyloside used. With 0.2mM xyloside radioisotope incorporation into keratan sulphate was not altered but inhibition was observed at xyloside concentrations of 1.0mM or higher. The decrease in radioisotope incorporation into keratan sulphate in the presence of 1.0mM benzyl beta-xyloside was directly related to a reduction in the average length of the keratan sulphate chains. This effect of beta-xyloside on keratan sulphate biosynthesis was markedly different from its effect on chondroitin sulphate biosynthesis. PMID- 6240271 TI - [Effect of procaine, nicotinoylprocaine and butacaine on mammalian cells in culture]. AB - The tertiary amines, procaine and nicotinoylprocaine, cause an increase in the specific activities of two glycohydrolases, alpha-fucosidase and beta-N acetylhexosaminidase, which are involved in membrane metabolism. The specific activity of alkaline phosphatase, a plasma membrane enzyme, is lowered in muscle cells after addition of procaine or nicotinoylprocaine to the culture medium. The specific activities of two transferases, aspartate-amino-transferase and creatine phosphokinase, are increased by 10(-5) mol/l butacaine. A combined addition of butacaine and nicotinoylprocaine causes less effects on the transferases. The specific activities of neutral alpha-glucosidase and beta-N-acetylhexosaminidase are scarcely influenced by butacaine alone. Only butacaine and nicotinoylprocaine together lead to an increase of the activities of these hydrolases. These results suggest two different mechanism of action at least concerning these substances: 1. a specific binding of tertiary amines and 2. a coordinated mechanism on the membrane fluidity. PMID- 6240272 TI - [Developmental pediatrics: the new pediatrics. Notes on its development]. PMID- 6240273 TI - [Causes of visual deficiency in children]. PMID- 6240275 TI - [Health and population]. PMID- 6240274 TI - [Home accidents in children under 5 years of age in Trujillo, Peru]. PMID- 6240276 TI - [Congenital cardiopathies in Down's syndrome]. PMID- 6240277 TI - [Cosmetic acne and a test of comedogenicity]. AB - A comedogenic test was carried out on the internal ear canal of four adult, masculine, albino rabbits, using butter of cacao and linseed oil, both known to be present in various cosmetic products. Histologic observation after 14 days showed follicular hyperkeratosis conferming the validity of this test. PMID- 6240278 TI - [Histopathological study on the fetus of Sanfilippo B disease]. PMID- 6240279 TI - [A case of Down syndrome with "moyamoya" disease: a consideration on fibromuscular dysplasia]. PMID- 6240280 TI - Measurement of platelet life-span in normal subjects and patients with myeloproliferative disease with indium oxine labelled platelets. AB - The use of 111Indium oxine as a platelet label for the performance of platelet life-span studies has been examined. Platelet life-span in normal subjects varied between 8 X 10 and 10 X 36 d. Patients with primary thrombocythaemia had clearly reduced platelet life-span whether or not they presented with vascular occlusion and this abnormality persisted after reduction of the platelet count to normal by busulphan therapy. Patients with similarly elevate platelet counts due to chronic granulocytic leukaemia or after splenectomy had platelet life-span values in the normal range. Plasma beta-TG levels could not be used to predict platelet life span in these groups of patients. Measurement of platelet life-span using 111Indium labelled platelets is a useful technique in the examination of platelet function in occlusive vascular disease. PMID- 6240281 TI - The effect of exogenous hormones on the resistance of the early pregnant human cervix. AB - The force required to dilate the cervix to a diameter of 8 mm (cervical resistance index) has been measured in 355 patients undergoing suction termination in the first trimester of pregnancy. The cervical resistance index (CRI) was significantly lower in multigravid patients compared with primigravid patients. Prior treatment with prostaglandin E2 pessaries produced a consistent reduction in CRI in multigravidae but not in primigravidae. The effect of the prostaglandin was more pronounced on the compliance of the cervical tissue than on the diameter of the cervical canal. Treatment with pessaries of oestradiol, progesterone and medroxy-progesterone acetate produced no changes in the CRI. PMID- 6240282 TI - [Dependence of ADP-ribosylation of histones of chicken liver nuclei on the intranuclear content of NAD]. AB - The dependence of ADP-ribosylation of chicken liver nuclear histones on NAD concentration in the nuclei was studied under conditions of stimulation of coenzyme synthesis by the nicotinamide and nicotinic acid as well as upon addition of various concentrations of the [Ado-U-14C]NAD nuclei to the incubation mixture. In the first case, the rate of [Ado-U-14C]NAD incorporation into the histones was decreased due to the dilution of the label by the de novo synthesized NAD. The amount of the latter formed under effects of nicotinic acid and nicotinamide increased, correspondingly, from 2,2 X 10(-5) mmol up to 4.1 X 10(-5) and 7.0 X 10(-5) mmol per mg of nuclear protein. The incorporation of [Ado U-14C]NAD into the histones decreased from 12.0 X 10(-8) mmol after incubation of liver slides with nicotinic acid and nicotinamide down to 8.0 X 10(-8) and 7.0 X 10(-8) mmol, respectively. With a rise in the concentration of exogenous [Ado-U 14C]NAD, the level of ADP-ribosylation of nuclear histones increased, the plot [14C]NAD incorporation at the labeled coenzyme concentration of 25 X 10(-7) mM/mg of histone had a plateau. Changes in the labeled substrate concentration brought about corresponding changes in the average length of the histone-linked poly-(ADP ribose) chain. PMID- 6240283 TI - [Antifibrinolytic effect of heparin]. AB - The effect of heparin on non-stabilized fibrin hydrolysis by plasmin was investigated. Using analytical centrifugation in the presence of heparin, the existence of a high molecular weight fraction (sedimentation coefficient 17S) was demonstrated. Electrophoretic analysis revealed the presence of less degradable early, intermediate and late fibrin hydrolysis products. It is concluded that the molecular mechanisms of these effects are due to the direct action of heparin on the fibrin-monomer molecule which provides for the inhibition of peptide side chains localized between residues 15 Gly-53 Lys in the NH2-terminal part of the B beta-chain. The universal mechanisms underlying the anti-fibrinolytic activity of high molecular weight inhibitors of fibrin polymerization and aggregation are discussed. PMID- 6240284 TI - Distribution of steroid sulfotransferase in the male hamster reproductive tract. AB - Steroid sulfotransferase activity has been assayed in cytosol extracts obtained from the male hamster reproductive tract. Dehydroisoandrosterone and desmosterol were used as substrates in the presence of phosphoadenosine phosphosulfate-35S as sulfate donor. No significant sulfotransferase activity was found in the testis. In the epididymis, a severalfold increase in activity was found in the tissue from the caput to the caudal regions. A lower but significant activity was detected in the vas deferens. The enzyme appears to be secreted into the luminal fluid while little activity is associated with the spermatozoa. This increase in activity along the epididymis is undoubtedly responsible for the accumulation of sterol sulfates reported previously. In view of the fact that sterol sulfates are potent and specific inhibitors of acrosin, as reported for the porcine and confirmed herein for hamster acrosin, the epididymal production of steroid and sterol sulfates may represent a protective mechanism against the premature release of proteolytic activity within the male reproductive tract. PMID- 6240285 TI - Voltage-dependence of Ca2+ uptake and ATP hydrolysis of reconstituted Ca2+-ATPase vesicles. AB - Ca2+-ATPase from sarcoplasmic reticulum was reconstituted into phospholipid/cholesterol (9:1) vesicles (RO). Sucrose density gradient centrifugation of the RO vesicles separated a light layer (RL) with a high lipid/protein ratio and a heavy layer (RH). RH vesicles exhibited a high rate of Ca2+-dependent ATP hydrolysis but did not accumulate Ca2+. RL vesicles, on the other hand, showed an initial molar ratio of Ca2+ uptake to ATP hydrolysis of approximately 1.0. Internal trapping of transported Ca2+ facilitated studies over periods of several minutes. Ca2+ transport and ATP hydrolysis declined concomitantly, reaching levels near 0 with external Ca2+ concentrations less than or equal to 2 microM. Ca2+ uptake was inhibited by the Ca2+ ionophore A23187, the detergent Triton X-100, and the metabolic inhibitor quercetin. Ca2+ transport generated a transient electrical potential difference, inside positive. This finding is consistent with the hypothesis that the Ca2+ pump is electrogenic. Steady state electrical potentials across the membrane were clamped by using potassium gradients and valinomycin, and monitored with voltage-sensitive dyes. Over a range of +50 to -100 mV, there was an inverse relationship between the initial rate of Ca2+ uptake and voltage, but the rate of ATP hydrolysis was nearly constant. In contrast, lowering the external Ca2+ concentration depressed both transport and ATP hydrolysis. These findings suggest that the membrane voltage influences the coupling between Ca2+ transport and ATP hydrolysis. PMID- 6240286 TI - Human red blood cell hemolysis in a turbulent shear flow: contribution of Reynolds shear stresses. AB - Various previous models used in studying red blood cell (RBC) hemolysis in turbulent shear flows are reviewed from a fluid dynamic point of view. The effect of turbulent shear stress (Reynolds shear stress, tau R) on RBC hemolysis is investigated utilizing a submerged axisymmetric jet flow field. A detailed survey of the flow field is made with a laser Doppler anemometer system to obtain contour maps of the mean velocity distributions, relative turbulence intensities, and tau R distributions in the field prior to conducting the experiment of sampling and analyzing the cells free-hemoglobin in the field. A new two-point sampling technique, developed in this laboratory, allows collections of RBC samples from selected locations in the flow field so that a relationship between the local shear stress level and the cell damage may be established. The threshold level of tau R responsible for incipient hemolysis is found to be approximately 400 Newtons per square meter (N/m2), below which a sublethal region of zero hemolysis is observed. PMID- 6240287 TI - [An unusual form of laparoschisis. Contribution to the embryological study of the umbilical region]. AB - The authors report one case of laparoschisis with special anatomic peculiarities: it was not defect on the abdominal wall, the intestinal evisceration go through a cordonnal defect who was distand of the normal abdominal wall and umbilicus. This observation re-opens the whole question of the abdominal wall deformities and all the embryologic theories are discussed. PMID- 6240288 TI - The epidemiology and toxicology of TCDD. PMID- 6240289 TI - Human effects of TCDD exposure. PMID- 6240291 TI - The effect of bronchodilator drugs on breath-holding capability in asthma. AB - A method of assessing the relationship between maximum voluntary breath-holding time (BHT) and the partial pressure of end-tidal carbon dioxide (PETCO2) during hyperoxic carbon dioxide rebreathing is described. The resulting index is referred to as the breath-holding capability (BHC). BHC and the maximum rate of early inspiratory pressure fall at the mouth while breathing oxygen at rest (RHdP/dtmax) were measured in normal and asthmatic subjects before and after treatment with nebulized solutions of salbutamol and ipratropium bromide. BHC was low in asthmatics when their airflow resistance was high and rose when the airflow resistance fell as the result of treatment; RHdp/dtmax was high in the asthmatics before treatment and fell after bronchodilator drugs were administered. The fall in respiratory drive which followed bronchodilatation in the asthmatic subjects cannot be solely explained in terms of the resulting fall in viscous and elastic work of breathing. Vagal afferent signals arising in the airways might play a part in modifying respiratory drive in such circumstances. PMID- 6240290 TI - Determination and measurement of human exposure to the dibenzo-p-dioxins. PMID- 6240292 TI - The individuality of chest wall motion in tetraplegia. AB - We have studied the motion of the chest wall in eight supine tetraplegic subjects using optical contour mapping. Measurements were obtained during quiet breathing, exaggerated breathing, during the course of a deep inspiration and during static inspiratory efforts. The pattern of motion showed a high degree of individual variability which did not appear to be related to the age of the patient, the duration of injury or the presence of intercostal muscle spasticity. By contrast, it did appear to be related to the presence of bony rib cage stiffness, and possibly the action of the neck accessory muscles. The pattern of rib cage motion in tetraplegia is more complex than conventionally thought. PMID- 6240293 TI - M. Evangeline Jordon, pioneer in pedodontics. PMID- 6240294 TI - The role of carbohydrates on cell recognition. Endogenous lectins. Proceedings of an international meeting. Aussois (France), March 1984. PMID- 6240295 TI - What lectins and carbohydrates are made for? PMID- 6240296 TI - Coordination between enzyme specificity and intracellular compartmentation in the control of protein-bound oligosaccharide biosynthesis. AB - This laboratory has developed schemes for the control of biosynthesis of N- and O glycosyl oligosaccharides based on studies in cell-free systems of glycosyl transferase substrate specificities. These schemes are based on assumptions that may not be universally correct. For example, we have ignored the possible compartmentation of reactions in different cells or in different organelles within a cell. Recent evidence has indicated that the Golgi apparatus has at least three functionally distinct regions (cis, medial and trans). The addition of galactosyl and sialyl residues to the antennae of complex and hybrid N-glycans probably occurs entirely within the trans-cisternae while the N acetylglucosaminyl-transferases which initiate these antennae appear to be located in a denser region of the Golgi (cis and/or medial cisternae). We have constructed a modified scheme for the biosynthesis of the antennae of N-glycans. This scheme combines our substrate specificity data (H. Schachter, S. Narasimhan, P. Gleeson and G. Vella, 1983, Can. J. Biochem. Cell Biol., 61, 1049-1066) with compartmentation data. It provides a basis for understanding the control of glycoprotein synthesis in normal tissues and in certain lectin-resistant mutant cell lines. PMID- 6240297 TI - Estimating glycoprotein carbohydrate chain structures by lectin reactivities in polyacrylamide gels. AB - Complex mixtures of cellular glycoproteins contain a myriad of different carbohydrate chains that cannot be easily analyzed without rigorous purification of each individual glycoprotein. We have analyzed the carbohydrate chains in complex mixtures of cellular glycoproteins by separation using sodium dodecyl sulfate polyacrylamide gel electrophoresis and interacting the gels with several 125I-labeled lectins. By use of in situ chemical modifications of the glycoproteins after their electrophoretic separation together with the known carbohydrate-binding specifities of several lectins, it has been possible to estimate glycoprotein carbohydrate chain structures. As an example we have examined the cellular glycoproteins of a ovary-colonizing metastatic variant of B16 melanoma and report the types of carbohydrate chains that are found on various melanoma glycoproteins. PMID- 6240298 TI - Localization of soluble endogenous lectins and their ligands at specific extracellular sites. AB - Soluble lectins of chicken, rat, frog, and the cellular slime mold, Dictyostelium discoideum, were purified and specific antibodies raised against these proteins were used to immunohistochemically localize the lectins in and around the tissues in which they were synthesized. Within cells, some of these soluble lectins (chicken-lactose-lectin-II in intestinal goblet cells, discoidin II in prespore cells) appear to be concentrated within vesicles whereas others (e.g., rat beta galactoside lectin in pulmonary alveolar and smooth muscle cells) appear to be free in the cytoplasm. All of these lectins are eventually secreted to extracellular sites in developing or adult tissues. The sites include mucin (chicken-lactose-lectin-II in intestine); developing extracellular matrix (chicken-lactose-lectin-I in muscle; Xenopus laevis lectin in blastula stage embryos); slime (discoidin I); developing spore coat (discoidin II); and a specialized extracellular matrix, elastic fibers (rat beta-galactoside lectin in lung). In cases where this has been studied in detail (discoidin I, discoidin II, and chicken-lactose-lectin-II), the lectin is associated with a complementary extracellular ligand, at least transiently. Lectin-ligand interactions presumably confer specialized properties in these particular extracellular domains. PMID- 6240299 TI - Inhibition of the endocytic pathway for asialoglycoprotein catabolism. AB - Rat hepatocytes in primary culture bind, internalize and eventually degrade asialoglycoproteins. This process is mediated by a specific receptor in the hepatocyte plasma membrane. The endocytic pathway by which ligand molecules are translocated to lysosomes has been examined by the development of biological assays capable of distinguishing ligand populations at various points in the process. Inhibitors have been identified that perturb particular transitions that define the endocytic pathway. In the present paper, inhibition by the bacterial tripeptide leupeptin is compared to the effect of colchine plus cytochalasin B. The latter combination impedes intracellular segregation of ligand and receptor while leupeptin inhibits intralysosomal proteolysis. However, evidence is presented to indicate that the inhibitory effects colchine plus cytochaasin B consists of at least two components. One component is independent of the presence of ligand whereas the other is observed only when ligand is present together with the drugs. PMID- 6240300 TI - Semliki Forest virus penetration from endosomes: a morphological study. AB - The low pH dependent membrane fusion reaction responsible for the delivery of the Semliki Forest virus genome into the host cell for replication was visualized by electron microscopy. In order to increase the frequency at which fusion images could be detected a reversible inhibitor, ammonium chloride, was used to synchronize endosomal acidification, and 20 degrees C incubation was employed to concentrate virus particles into the endosomal compartment. PMID- 6240301 TI - Uptake of neoglycoproteins via membrane lectin(s) of L1210 cells evidenced by quantitative flow cytofluorometry and drug targeting. AB - The presence and the sugar specificity of membrane lectins on the cell surface of mouse L1210 leukemia cells were demonstrated by using various neoglycoproteins (glycosylated serum albumin) substituted with fluorescein or methotrexate. Neoglycoproteins were prepared by reaction of glycosidophenylisothiocyanates with bovine serum albumin. The binding of neoglycoproteins to L1210 cells depends on the nature of the carried sugar and on the number of bound sugar residues per neoglycoprotein molecule. The best results were obtained with fucosylated serum albumin containing 25 +/- 5 residues of fucose. The amount of cell-associated fluorescein-labeled neoglycoproteins was several fold higher at 37 degrees C than at 4 degrees C suggesting a specific endocytotic process. The membrane lectin mediated endocytosis was further demonstrated by showing that the cell-associated fluorescence upon cell incubation in the presence of fluorescein-labeled neoglycoproteins at 37 degrees C increased several fold after addition of monensin, a proton/sodium ionophore known to raise the pH of endosomes and lysosomes. The analysis of fluorescein-labeled neoglycoproteins association to the L1210 cells were achieved by quantitative flow cytofluorometry after standardization with calibrated polystyrene sulfonate beads carrying various amounts of 1-(fluoresceinylthioureido)-4,8-diazalicosane. In addition, the cytotoxicity of neoglycoprotein-bound methotrexate was shown to be related to the presence and to the nature of the carried sugar: fucosylated serum albumin was shown to be the most efficient neoglycoprotein carrier, and to have a cytotoxicity close to that of anti L1210 cell IgM monoclonal antibody carrying methotrexate. PMID- 6240302 TI - An endogenous carbohydrate-binding agglutinin of BHK cells. Purification, specificity and interaction with normal and ricin-resistant cell lines. AB - Several lectin-like activities were detected on the surface of unfixed, viable BHK cells by reaction with FITC-labelled glycosylated albumin derivatives. A prominent surface staining was obtained with the beta-lactosyl, beta-N acetylgalactosaminyl, alpha-mannosyl and beta-N-acetylglucosaminyl derivatives. Endogenous lectin-like activities were also detected in BHK cell homogenates by haemagglutination of glutaraldehyde-fixed rabbit erythrocytes. Haemagglutinating activity was purified by chromatography of sodium deoxycholate-extracts of BHK cell microsomal fractions on Sepharose 4B and asialofetuin-Sepharose 4B. A purified agglutinin was eluted from the latter column with 0.2 M thiodigalactoside. The haemagglutination mediated by the purified factor was inhibited by thiodigalactoside, N-acetylgalactosamine, galactosyl-beta 1-4-N acetylglucosamine and several glycoproteins. The purified agglutinin agglutinated trypsinised, fixed normal BHK cells more readily than several ricin-resistant cell lines. By contrast, a mannose-binding lectin from rabbit serum reacted equally well with normal and mutant cells. These results are in general agreement with models of cell-cell adhesion involving the interaction of surface located lectins with carbohydrate sequences of normal BHK cell surface glycoproteins. PMID- 6240303 TI - The mannose 6-phosphate receptor: function, biosynthesis and translocation. AB - This report summarizes studies concerning the role of the lysosomal protein: Man 6-P receptor and describes some recent data on its biosynthesis and cellular translocation. The receptor functions both in the Golgi apparatus (or GERL) and on the cell surface where it binds lysosomal proteins and mediates their transport to lysosomes. Consistent with its dual role, the receptor in several cell types has been localized to the plasma membrane and Golgi cisternae, to clathrin-coated structures at both locations, and to vesicles characteristic of endosomes or CURL. Biosynthetic studies have shown that the receptor undergoes several post-translational modifications including the processing of its asparagine-linked oligosaccharides, phosphorylation of serine residues, and unknown modifications required for acquisition of immunoreactivity and functional activity. Cellular pools of mature receptor readily mix as evidenced by rapid labeling of intracellular receptor by exogenously added receptor antibodies. Degradation of the receptor occurs non-lysosomally and is perhaps mediated by extracellular Man-6-P-containing hydrolases. A working hypothesis for the mechanism of Man-6-P receptor function that is consistent with these observations is presented. PMID- 6240304 TI - Mannose-specific oligosaccharide recognition by mononuclear phagocytes. AB - Glycoproteins terminating in mannose are recognized by receptors on macrophages. The mannose receptor is expressed by a variety of macrophages but expression is closely regulated. Activated macrophages, for example, express little mannose receptor activity. Kinetic and fractionation experiments suggest that cell surface mannose receptors recycle to and from an acidic, pre-lysosomal compartment. Preliminary evidence suggests that the mannose receptor is a large polypeptide and that it is structurally related to the mannose binding protein found in serum. The mannose receptor may, among other possibilities, regulate the extracellular levels of lysosomal hydrolases. PMID- 6240305 TI - GalNAc/Gal-specific rat liver lectins: their role in cellular recognition. AB - By investigating the presence and distribution of GalNAc/Gal-specific receptors on liver cells in vitro and in vivo, we provided evidence that the hepatocyte is not the only liver cell expressing receptor activity but that receptors of similar specificity are found on liver macrophages and also on endothelial cells. The receptor distribution in the plasma membrane is strinkingly different between the three cell types, as judged from the binding pattern of colloidal gold particles coated with asialofetuin or lactosylated serum albumin. Binding to hepatocytes occurs as single particles statistically distributed, binding to liver macrophages in a clustered arrangement all over the cell membrane and binding to endothelial cells also in a clustered arrangement but restricted to coated pits only. The different receptor distribution results in different binding and uptake abilities. Whereas hepatocytes bind and take up molecules and small particles (5 nm) only, the clustered receptor arrangement of endothelial cells and macrophages enables them to effectively bind and ingest larger particles. Ligands larger than 35 nm can be taken up by the macrophages only. The different receptor arrangement results also in different capacities of cell contact formation. Although in vitro liver macrophages and hepatocytes can both bind desialylated cells the macrophage needs much less galactosyl groups exposed on erythrocytes to establish stable contacts than the hepatocyte. The contacts formed by hepatocytes stay reversible for 30 min at 37 degrees C, whereas the contacts formed by the liver macrophages become irreversible after 10 min at 37 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 6240306 TI - The recognition of red blood cells by macrophages: role of phosphatidylserine and possible implications of membrane phospholipid asymmetry. AB - The recognition of phosphatidylserine (PS) by macrophages was investigated using inside-out (IO) red blood cell (RBC) ghosts and RBC displaying PS in their surface membranes. This was accomplished by employing unmodified pathologic sickle RBC which contain endogenous PS in their outer membrane leaflet, and RBC modified by the transfer of an exogenous fluorescent PS analog. Proper insertion of exogenous PS was confirmed by monitoring the degree to which cell-associated lipid fluorescence was dequenched following transfer of 1-acyl-2-[(N-4-nitro benzo-2-oxa-1,3 diazole) aminocaproyl] phosphatidylserine (NBD-PS) from a population of self-quenched donor vesicles. Inside-out RBC ghosts were endocytosed approximately 3 times faster than were right side-out control populations. Similarly, using NBD-PS vesicles at concentrations at which dilution of all the cell-associated analog in the recipient RBC could be unequivocally confirmed, we observed that the uptake of NBD-PS treated RBC by macrophages was significantly increased over that of control RBC populations. Fluorescence and electron microscopic observations revealed the formation of typical RBC macrophage rosettes that were morphologically distinct from opsonized RBC macrophage rosettes. Enhanced RBC binding to macrophages was also obtained with deoxygenated reversibly sickled cells (RSC); the enhancement correlated with increased exposure of outer leaflet PS in these cells. These findings suggest that PS is recognized by macrophages and that its exposure in the outer leaflet of RBC may have significant pathophysiologic implications. PMID- 6240307 TI - Carbohydrates as recognition determinants in phagocytosis and in lectin-mediated killing of target cells. AB - Carbohydrate-lectin interactions serve as the basis of recognition by phagocytic cells of particles and of various target cells. Such interactions occur in the following systems: between sugars on the surface of the phagocytic cells and lectins on the surface of other cells--the best studied example is the binding of mannose-specific Escherichia coli and related organisms via their surface lectins to oligo-mannose residues on macrophages; between lectins on the surface of phagocytic cells and sugars on particles or other cells--phagocytosis of zymosan and of sialidase-treated erythrocytes, mediated respectively by mannose-specific and galactose-specific lectins on macrophages, belongs to this category; by extracellular lectins that form bridges between sugars on both types of cell--as shown by enhancement of phagocytosis of staphylococci by wheat germ agglutinin, and by lectin-dependent killing of target cells by macrophages. These interactions may play an important role in the activities of phagocytic cells in vivo. They may provide an initial host defense mechanism immediately after microbial infection, operate in tissues where phagocytic activity is poor, and participate in tumor rejection. PMID- 6240308 TI - The role of carbohydrate in heterotypic cell-cell recognition: lymphocyte-high endothelial cell interaction as a model system. AB - The studies reviewed here demonstrate that the interaction of lymphocytes with HEV is one of the most approachable models available for the study of heterotypic cell-cell recognition mechanisms. Lymphocyte-HEV interaction is mediated by specific lymphocyte surface receptors recognizing, by as yet unknown mechanisms, determinants expressed by specialized high endothelial cells in lymphoid tissues and sites of chronic inflammation. Both the lymphocyte and endothelial cell surface elements of the interaction are precisely regulated, controlling the traffic of lymphocyte subsets through particular lymphoid organs and into sites of inflammation. Considerable progress, reviewed here, has been made in defining and characterizing the lymphocyte surface molecules mediating this cellular interaction. By contrast, the nature of the endothelial cell determinants recognized by migrating lymphocytes remains a mystery. Future experiments must be designed to identify these endothelial cell determinants, and to examine critically a proposed role of carbohydrate in lymphocyte-HEV interaction. PMID- 6240310 TI - European Tissue Culture Society (ETCS). 32nd meeting, Milan, September 10-13, 1984. Abstracts. PMID- 6240309 TI - Binding of bacteria in lymphocyte subpopulations: role of lectin-carbohydrate interactions. AB - Bacteria have been found to bind to lymphocyte subpopulations in a highly reproducible manner. Some of these bacteria such as B. melitensis and a strain of E. coli binds to mammalian B. cells. The binding of B. melitensis and other bacteria is due, at least in part, to lectins on lymphocytes interacting with the carbohydrates on the LPS or LTA of the bacteria. These receptors for bacteria give some indications regarding the functional potential of the cells, suggesting the possibility that the receptors identified by bacteria are used in cellular interactions with normal or malignant cells. PMID- 6240311 TI - Susceptibility to antimicrobials of Neisseria gonorrhoeae isolated in Singapore: implications on the need for more effective treatment regimens and control strategies. AB - The antimicrobial susceptibility of gonococci isolated in Singapore has been studied over several years. In 1983, the prevalence of penicillinase producing Neisseria gonorrhoeae (PPNG) was 33.5% and 64% of non-PPNG isolates had minimum inhibitory concentrations (MICs) of penicillin of greater than or equal to 0.5 mg/l. After a control programme, the isolation of the gonococcus from prostitutes was reduced and there was improvement in its susceptibility to antimicrobials. The incidence of PPNG strains was stabilised with a change in the treatment regimen. An influx of foreign prostitutes, however, had an unfavourable impact on these variables. Countries in South East Asia have a high prevalence of PPNG and non-PPNG strains that have reduced susceptibility to antimicrobials. In view of increased air travel the problem should be seen from a global perspective. Better treatment regimens and control strategies are urgently needed. PMID- 6240312 TI - Endogenous infection in mice with streptozotocin-induced diabetes. A feature of bacterial translocation. AB - Slc:ddY mice that received a single intraperitoneal injection of 200 mg/kg streptozotocin (STZ) were examined for persistency of diabetes (changes of indigenous bacterial floras, and bacterial translocation. Significant diabetes (increase in plasma glucose and decrease in insulin) was recognized 2 weeks after the injection, and persisted for 12 weeks. The numbers of aerobic gram-negative bacilli, staphylococci (including micrococci), and streptococci in caecal and oral floras were significantly increased, but the numbers of anaerobic bacteria in caecal flora were hardly changed. Bacterial translocation of indigenous bacteria to the mesenteric lymph node, lung, or kidney was detectable in some mice 2 weeks after the injection. The incidence of bacterial translocation in these STZ-treated mice then increased; infection caused by several organisms, e.g., Klebsiella pneumoniae, Staphylococcus epidermidis, streptococci, or Lactobacillus sp., occurred in lung, liver, spleen, kidneys, and mesenteric lymph node. No indigenous bacteria were cultured from these organs of control mice. This endogenous infection may have been due to the over population of several bacterial strains caused by disruption of indigenous floras along with depression of immunological function. PMID- 6240313 TI - Genetic linkage of the Huntington's disease gene to a DNA marker. AB - Recombinant DNA techniques have provided the means to generate large numbers of new genetic linkage markers. This technology has been used to identify a DNA marker that coinherits with the Huntington's Disease (HD) gene in family studies. The HD locus has thereby been mapped to human chromosome 4. The discovery of a genetic marker for the inheritance of HD has implications both for patient care and future research. The same approach holds considerable promise for the investigation of other genetic diseases, including Dystonia Musculorum Deformans. PMID- 6240315 TI - [Laparoscopic diagnosis of primary carcinoma of the liver]. PMID- 6240314 TI - Cardiac performance and myocardial blood flow in pigs with compensated right ventricular hypertrophy. AB - Compensated right ventricular hypertrophy (RVH), defined by a greater than 100% RV weight increase compared to 17 normal animals, was created in 17 young pigs by pulmonary arterial banding. RVH was associated with significant elevations (p less than 0.001) in RV peak dP/dt, RV stroke work, RV minute work and RV rate pressure product compared to normal animals matched by body weight. RV peak dP/dt showed a positive correlation (p less than 0.001) with RV peak systolic pressure in normals; however, this relationship was lost in banded animals since progressively higher RV pressures were not associated with concomitant increases in RV peak dP/dt, thus, suggesting an intrinsic difference between right and left ventricles when working at systemic arterial pressures. Time to RV peak dP/dt became progressively longer (p less than 0.05) as RV weight increased in the RVH animals. When indices of cardiac work were normalized for RV weight, the RVH group could not be distinguished from normals suggesting that the performance per unit weight of RV muscle in RVH was unchanged. Total RV blood flow, measured by radioactive microspheres, closely followed (p less than 0.001) increases in RV mass in banded animals. Blood flow . g-1 muscle in RV and septal right side were unaltered in RVH; however, regional perfusion of the left ventricle (p less than 0.001) and septal right side were unaltered in RVH; however, regional perfusion of the left ventricle (p less than 0.001) and septal left side (p less than 0.02) increased significantly. There were regional variations in RV perfusion which were maintained in compensated RVH; stress (isoprenaline infusion) caused significant increases in blood flow to all regions of the heart in normal and RVH animals (p less than 0.001), but relative regional distribution was maintained. Our observations suggest a relationship between myocardial work and blood flow in RVH such that RV perfusion . g-1 is elevated to meet haemodynamic requirements once RV regional work . g-1 become greater than normal. PMID- 6240316 TI - The calcium hypothesis of cystic fibrosis. AB - Data have been presented which suggests that various CF cell types show evidence of alterations in calcium homeostasis. The significance of these observations and the exact nature of the putative calcium defect in CF remains to be elucidated. It must also be determined whether this possible defect is primary, or is secondary or tertiary to some more basic lesion. The data reviewed suggests that altered calcium homeostasis may play some focal role in the aetiology or the pathogenesis of CF. PMID- 6240317 TI - Effect of trifluoperazine, compound 48/80, TMB-8 and verapamil on ionophore A23187 induced calcium transients in human red cells. AB - A transient increase of cellular calcium was induced by addition of the divalent cation ionophore A23187 to human red cells in the absence or presence of drugs. The peak height of the calcium transient was increased about five times at pH 6.9 and up to eighteen times at pH 7.4 by trifluoperazine (0.30 mM), and two to three times at pH 6.9 by compound 48/80 (0.89 mg/ml), 8-(N,N-diethylamino)octyl-3,4,5 trimethoxybenzoate (TMB-8, 2.13 mM) and verapamil (1.81 mM). The time-dependent changes of cellular calcium were analysed by the aid of a pump-leak model based partly on the calcium dependent parameters obtained from calcium ATPase experiments, partly on the A23187 induced calcium fluxes determined in experiments with ATP depleted cells. The transient increase of cellular calcium induced within few minutes after the addition of ionophore A23187 could be explained satisfactorily by the model both in the absence and presence of the four drugs, whereas the final level of cellular calcium in the drug experiments was more difficult to predict from the pump-leak model. Comparison of experimental and model calcium transients suggested that trifluoperazine and TMB 8 affected both pump and leak, whereas compound 48/80, probably due to low membrane-permeability, mainly affected the leak and verapamil affected the pump only. PMID- 6240319 TI - Experience with a technique for coronary angioplasty of bifurcational lesions. AB - To decrease the risk of iatrogenic side branch occlusion during coronary angioplasty of bifurcational lesions, we evaluated a technique in which two over the-wire dilatation systems are positioned within the stenosed coronary artery and the side branch in jeopardy. The technique was used in eight patients undergoing angioplasty for a lesion in the left anterior descending or circumflex artery located near a large side branch. Successful dilatation of the major vessel lesion was achieved in all eight patients, and dilatation within the side branch was successful in all three patients whose lesion involved the side branch ostium. In one patient, dilatation within the major vessel led to partial closure of the side branch and the prepositioned guide wire facilitated prompt dilatation of the iatrogenic closure. There were no complications associated with use of the additional dilatation system. The technique appears to provide an efficacious method to perform safe coronary angioplasty in selected patients with bifurcational lesions. PMID- 6240318 TI - Effect of in vivo changes in phospholipid composition on liver microsomal calcium transport. AB - We recently reported that the phospholipid composition of mouse liver microsomes could be altered in vivo by a combination of dietary choline deprivation and administration of the methylation inhibitors periodate-oxidized adenosine and cycloleucine (D.M. Boyle & W.L. Dean (1982) Biochim. Biophys. Acta 688, 667-670). We have now determined the effect of this in vivo change in phospholipid composition on 7 microsomal enzyme activities and 2 cytochromes. The specific contents of cytochromes b5 and P-450 were unaffected by the treatment. Similarly, NADH-cytochrome c reductase, cytochrome P-450 reductase, cyclohexane hydroxylase and Mg2+-ATPase were not significantly altered. In addition, the phospholipid/protein ratio was not changed. In contrast, Ca2+-ATPase and Ca2+ transport rates were reduced by more than 60%. This result suggests that the mouse liver microsomal Ca2+-ATPase is extremely sensitive to the phospholipid composition of the membrane in which it is embedded and that one mode of control of calcium metabolism in liver cells could be at the level of membrane phospholipid composition. PMID- 6240320 TI - A simple technique for location of the coronary stenotic lesion in percutaneous transmural coronary angioplasty. AB - We have developed a technique (grid) for location of the stenotic coronary lesion in percutaneous transluminal coronary angioplasty (PTCA). It is simple, economical, and easy to use with no risk to the patient. Utilization of this technique provides for quick and accurate positioning of the balloon catheter in the coronary lesion during PTCA. PMID- 6240321 TI - [Disability due to diseases of the locomotor system in the Kosice-Vidiek District]. PMID- 6240322 TI - Effects of pH and ligands on the metals-catalyzed hydrolysis of clioquinol conjugates. PMID- 6240323 TI - Studies on metal-catalyzed hydrolyses of clioquinol conjugates in the rabbit body following intravenous injection of Cu(II)- or Fe(III)-gluconic acid complex system. PMID- 6240324 TI - [Research on Chinese drug compounds. I]. PMID- 6240325 TI - [Clinical efficacy of huxindan in patients with sick sinus syndrome]. PMID- 6240326 TI - [Clinical research on the hemostatic effect of rhubarb on peptic ulcer with acute bleeding]. PMID- 6240327 TI - [Retinal vein occlusion treated by bian zheng bian bing]. PMID- 6240328 TI - [Clinical analysis of 84 cases of glomerulonephritis treated with Tripterygium wilfordii]. PMID- 6240329 TI - [Clinical analysis of 10 refractory cases of idiopathic nephrotic syndrome in children treated with combined traditional Chinese medicine and western medicine]. PMID- 6240330 TI - [Hemodynamics and radial sphygmogram in hypertensive patients with different pathological conditions based on the differentiation of symptoms according to traditional Chinese medicine]. PMID- 6240331 TI - [Biological activities of Astragalus polysaccharides]. PMID- 6240332 TI - [Protective effect of qi-xue injections on rat liver damage induced by cortisone acetate--analysis of the stereometrical quantitation of ultrastructure]. PMID- 6240333 TI - [Treatment of ulcerative colitis with disodium cromoglycate enemas and Chinese medicine]. PMID- 6240334 TI - [Application of xuejie in oral and maxillofacial surgery]. PMID- 6240335 TI - [Interpreting the term "qi" in traditional Chinese medicine and the translation of Chinese medical terms]. PMID- 6240336 TI - [Development of medical English and the translation of Chinese medical terminology]. PMID- 6240337 TI - [Advances in the research on pyoderma treated by Chinese herbal drugs or combined traditional Chinese and western medicine in the last 30 years]. PMID- 6240338 TI - [Progress in the experimental research on the function of huo xue hua yu of Leonurus heterophyllus Sweet]. PMID- 6240339 TI - [Prospects for combined traditional Chinese medicine and western medicine in the treatment of acute abdomen]. PMID- 6240340 TI - [A preliminary study on catgut embedding at point sanyinjiao to induce ovulation]. PMID- 6240341 TI - [Clinical observations on 36 cases of viral myocarditis treated with Epimedium grandiflorum Moor and vitamin C]. PMID- 6240342 TI - [Treatment of acute bacillary dysentery with traditional Chinese medicine and western medicine combined--analysis of 117 cases]. PMID- 6240343 TI - [The relation between blood rheology and the differential diagnosis of chronic hepatitis and liver cirrhosis in Chinese medicine]. PMID- 6240344 TI - [Effect of single and combined Chinese drugs on hematopoietic cells]. PMID- 6240345 TI - [Effect of Salvia miltiorrhiza root on calcium deposition in experimental fracture healing]. PMID- 6240346 TI - [Experimental study on the effect of dried and prepared notoginseng on serum lipids]. PMID- 6240347 TI - [Effect of Salvia miltiorrhiza on mesenteric microcirculatory blood flow in the dog measured by the Doppler effect of laser light]. PMID- 6240348 TI - [Effect of Viscum coloratum (Kom) Nakai on changes in the cyclic nucleotides in ischemic myocardium]. PMID- 6240349 TI - [Electron microscopic observation on experimental myocardial atherosclerotic changes induced by shi xiao powder]. PMID- 6240350 TI - [A comparative study on the effect of 20 herbs activating blood circulation and decreasing blood stasis on the obstruction of experimental microcirculation]. PMID- 6240351 TI - [Antifungal activity of volatile oils in Litsea cubeba and its main constituent citral]. PMID- 6240352 TI - [Effect of Rheum palmatum L. on blood rheology in normal subjects]. PMID- 6240353 TI - [Clinical experience in the treatment of bronchial asthma]. PMID- 6240354 TI - [Treatment of peripheral vascular diseases with Chinese medicine]. PMID- 6240355 TI - [Study on the chemical composition and pharmacological effect of Ligusticum wallichii Franch]. PMID- 6240356 TI - [Purine metabolism in Schistosoma japonicum]. PMID- 6240357 TI - [Parasitism of human hair follicle mites and its relation to the histopathology of rosacea]. PMID- 6240358 TI - The renin-angiotensin system and hypertensive left ventricular hypertrophy in the rat. AB - The relationship between left ventricle-to-body weight ratio (LV/BW), mean arterial pressure (MAP, the average of 12 h of intra-arterial monitoring in conscious animals) and plasma renin activity (PRA) was assessed at 12 weeks after unilateral clipping or sham operation in twenty-four one-kidney rats and twenty six two-kidney rats. The degree of hypertension and left ventricular hypertrophy were similar in one-kidney and two-kidney groups. There was a close linear relationship between LV/BW and MAP which was similar in one-kidney and two-kidney rats. PRA was significantly elevated only in two-kidney rats and was not related to the degree of hypertrophy after accounting for the effect of PRA on MAP. These data suggest that activation of the renin-angiotensin system does not contribute directly to myocardial hypertrophy in rats with renal-clip hypertension. PMID- 6240359 TI - Hydralazine and lupus nephritis. AB - Renal involvement is uncommon in the hydralazine induced systemic lupus erythematosus syndrome. Six women with hypertension are described who developed an immune complex glomerulonephritis after taking 50-300 mg hydralazine daily for 6 months to 7 years. Associated features were anemia (100%), hypocomplementemia (50%), a positive antinuclear antibody test (100%) and antibodies to double stranded DNA (66%). All patients were slow acetylators and four had HLA-DR 4 genotype. Renal function deteriorated in all cases. Cessation of hydralazine combined with immunosuppressive therapy resulted in amelioration of the disease. It is likely that the patients had a hydralazine induced lupus glomerulonephritis, or alternatively had an unmasking of an inherent tendency to idiopathic lupus nephritis by hydralazine. PMID- 6240360 TI - [Communication by patients with late amyotrophic lateral sclerosis--a document creating system by input of muscular action potentials]. PMID- 6240361 TI - [Correlation between histological and biochemical findings in 6-aminonicotinamide induced spinal paralysis of rats and effect of TRH treatment]. PMID- 6240362 TI - [Untoward side effects of acetylsalicylic acid]. PMID- 6240363 TI - [Various clinical uses of dibromotyrosine in endocrine and inflammatory pathology of the thyroid]. PMID- 6240364 TI - [Use of cefuroxime in infective pluriorgan pathology. Observations on 60 cases]. PMID- 6240365 TI - [Evaluation of platelet aggregation in patients treated with ticlopidine]. PMID- 6240366 TI - [Premenstrual syndrome. Physiopathology, clinical aspects and therapy]. PMID- 6240367 TI - [Organ transplantation: results and new methods]. PMID- 6240368 TI - [Circadian variability of hydrosaluretic and antihypertensive effects of a single daily 25 mg. dose of chlorthalidone]. PMID- 6240369 TI - [Evaluation of the hemodynamic effects of acute infusion and short-term treatment with creatine phosphate]. PMID- 6240370 TI - [Clinical evaluation of metolazone in edematogenic syndromes]. PMID- 6240371 TI - [Idiopathic hypereosinophilic syndrome: diagnosis and therapy]. PMID- 6240372 TI - [Eating behavior and obesity]. PMID- 6240374 TI - Lichenoid drug reactions to chlorpropamide and tolazamide. AB - Many medications, including gold, antimalarials, quinidine, and thiazide diuretics have been implicated in lichenoid drug reactions. Chlorpropamide and tolazamide are sulfonylurea oral hypoglycemic agents, neither of which has previously been implicated in cutaneous lichenoid reactions. We report a case of lichenoid drug reaction related to both chlorpropamide and tolazamide. PMID- 6240373 TI - Dermatitis due to transdermal therapeutic systems. PMID- 6240375 TI - [Investigation of the method of double contrast examination of the colon]. PMID- 6240377 TI - [The angiographic evaluation of rejection of renal transplants]. PMID- 6240376 TI - [A hypotonic double-contrast examination of the stomach using 70 mm fluorography]. PMID- 6240378 TI - [X-ray diagnosis of 140 cases of intracranial aneurysm with emphasis on analysis of cerebral angiograms]. PMID- 6240379 TI - [Vertebral arteriographic changes in tumors of the cerebellopontine angle]. PMID- 6240380 TI - [Carotid arteriography in the diagnosis of nasopharyngeal cancer (an analysis of 21 cases)]. PMID- 6240381 TI - [Mediastinal tumor of vascular origin (a report of five cases)]. PMID- 6240382 TI - [Evaluation of the diagnostic capability of a counter table for solitary round shadows in the lung field]. PMID- 6240383 TI - [An analysis of radiologic signs of typical pulmonary calcification in 8 cases of paragonimiasis]. PMID- 6240384 TI - [Diagnostic problems concerning injury of occipito-atlanto-axial segment]. PMID- 6240385 TI - [Chest x-ray of severe steam burns of the respiratory tract]. PMID- 6240386 TI - [Problems in the design of an electric source for X-ray machines]. PMID- 6240387 TI - [The pathology and evolution of the X-ray signs of the bone and cartilage in Kaschin-Beck disease]. PMID- 6240388 TI - [Evolution of the X-ray signs and classification of Kaschin-Beck disease]. PMID- 6240389 TI - [Advances of pathologic research in Kaschin-Beck disease]. PMID- 6240390 TI - [Experiment in vitro with assessment of barium sulphate preparations]. PMID- 6240391 TI - The laminin receptor and basement membrane dissolution: role in tumour metastasis. AB - Tumour invasion and metastasis is a complex process involving multiple interactions of tumour cells with host cellular and extracellular elements. Metastasizing tumour cells traverse basement membranes at many stages in the metastatic cascade. Immunohistology studies demonstrate that the basement membranes are defective in all human malignant epithelial neoplasms studied to date. The basement membrane is absent in regions of microinvasion and adjacent to actively invading tumour cells. In contrast, benign neoplasms retain a continuous basement membrane. This distinction may have diagnostic value in surgical pathology. Tumour cells are hypothesized to traverse basement membranes by a three-step process: attachment, local degradation of the basement membrane by type IV collagenase and other proteases, and locomotion. The first step may be mediated in part by specific cell surface receptors which bind to laminin in the basement membrane. The laminin receptor has been purified from a series of different human carcinomas. The receptor has an Mr of 67 000 and a binding coefficient of 2 nM. The content of unoccupied receptors is markedly augmented in invasive human breast cancer compared to benign controls. PMID- 6240392 TI - The regulation of basement membrane formation and cell-matrix interactions by defined supramolecular complexes. AB - Several constituents of basement membranes, including type IV collagen, laminin, heparan sulphate proteoglycan and nidogen, form a defined supramolecular complex that is an obligatory intermediate in the formation of this matrix. We have named this defined supramolecular complex the 'basement membrane matrisome'. Matrisome structures composed of other collagens, proteoglycans and glycoproteins may participate in the formation of other extracellular matrices. Cells show specific interactions with components of the extracellular matrix. We discuss studies that indicate that melanoma cells can express receptors for both laminin and fibronectin. However, these receptors are expressed in a reciprocal fashion, depending on the exposure of the cell to these proteins. Binding of either fibronectin or laminin to the cells elicits a distinct phenotype. This represents a mechanism in which cellular activity can be regulated by extracellular matrix factors during development and in repair. PMID- 6240393 TI - [An experimental study on umbilical cord vessels as arterial grafts]. PMID- 6240394 TI - [A study of the relation between energy transduction ATPase of mitochondrial membranes and experimental silicosis]. PMID- 6240395 TI - Experimental maternal phenylketonuria: an examination of two animal models. AB - Two satisfactory rat models of maternal phenylketonuria (PKU) have been developed. Continuous subcutaneous infusion into pregnant rats from the 9th-20th day of gestation of either (1) phenylacetate (PA), to elevate plasma levels of unconjugated PA to 0.25-0.60 mumol/ml, or (2) a nontoxic dose (0.2 mumol/g/day) of p-chlorophenylalanine (pClPhe) with L-phenylalanine (Phe), to elevate plasma Phe levels at least 10-fold (1.7-2.3 mumol/ml) and unconjugated PA to at least 0.2 mumol/ml, produced the syndrome of untreated maternal PKU: spontaneous abortion, mortality rate greater than normal among the newborn, retarded growth of fetal body and brain, and a learning deficit among the progeny. From the plasma of rats infused with only pClPhe, a metabolite was isolated and identified as p-chlorophenylacetic acid. This compound, at a concentration greater than 0.15 mumol/ml plasma was found to retard fetal body and brain growth. In the pregnant rat, plasma levels of unconjugated PA, in the range observed in some PKU individuals on a normal diet, effectively induced a simulation of maternal PKU. The results of this investigation support our contention that PA, which is produced in excessive amounts in clinical PKU, is the primary cause of the brain dysfunction. PMID- 6240396 TI - The anecdotal antidotes. AB - The author reviews obscure or unusual antidote recommendations, emphasizing antidotes or antidote uses that are not generally acknowledged or that have little experimental or clinical confirmation of their efficacy. Also included are unusual uses of well known antidotes. Among the antidotes considered are naloxone, physostigmine, folate, Prussian blue, n-acetylcysteine, cimetidine, subcutaneous magnesium salts, nicotinamide, and thioctic acid. PMID- 6240397 TI - Low back pain. Evaluation and treatment in the emergency department setting. AB - The author outlines the most common clinical syndromes causing back pain, including degenerative disc disease, disc herniation syndrome, and cauda equina syndrome. Also discussed are specific guidelines regarding the need for immediate orthopedic and neurosurgical consultation or admission to the hospital. PMID- 6240398 TI - Percutaneous transluminal angioplasty for treatment of renal artery stenosis in children. AB - Angioplasty was carried out in four children with hypertension and renal artery stenosis, including one patient with neurofibromatosis and one patient with multiple arterial stenoses. Two patients did not respond. In the patient with neurofibromatosis the stenosis persisted unchanged despite multiple balloon inflations. In one patient hypertension persisted despite successful dilatation, and was probably related to longstanding contralateral kidney disease. Two patients had excellent blood pressure response to dilatation. One of these patients required redilatation of bilateral recurrent stenoses. PMID- 6240399 TI - Haemodynamics and durability of mitral bioprostheses--an in vitro study. AB - The haemodynamic characteristics and durability of mitral bioprostheses were evaluated and compared in vitro in a pulse duplicator and in a fatigue test system. Porcine xenografts were shown to be the most stenotic of all bioprostheses, studied at rates simulating both rest and exercise; on the other hand the new generation of biological valves showed a clear improvement in haemodynamics compared with the standard porcine and pericardial prostheses so far used clinically. Durability tests performed at a rate of 1600 to 1800 beats per minute and with a closing pressure ranging from 80 to 100 mmHg showed that the Ionescu-Shiley and Edwards pericardial xenografts last significantly longer than the Hancock and Carpentier Edwards porcine valves and Hancock pericardial bioprosthesis. Correlation between the mode of failure of pericardial and porcine valves in vitro and in vivo clearly demonstrates that a major role in valve failure is played by mechanical stress. This can be either a consequence of the continuous trauma sustained by the tissue hitting against the bare dacron cloth of the sewing ring during the movements of the cusps. or a result of fatigue occurring and the bending points of the leaflets. The results of this study underline the importance of a continued in vitro evaluation of both haemodynamics and durability of bioprostheses, since some of the pericardial valves which had the best haemodynamic performance showed the worst resistance to fatigue-induced failure. A careful selection of the tissue, modification of the stent design and avoidance of a dacron covered frame are suggested to improve long-term durability of biological prostheses. PMID- 6240400 TI - Gamma camera detection of 99mTC-plasmin in the diagnosis of deep-vein thrombosis. AB - 99mTc-Plasmin scintigraphy of suspected vein thrombosis registered by a gamma camera was compared with phlebography. The results indicate that the plasmin test can be an alternative method to phlebography. The plasmin test registered by a gamma camera has a high sensitivity but relatively low specificity; this agrees with the results of previous investigations regarding registration with a single detector. PMID- 6240401 TI - Improved lesion detection with dimethyl-amino-diphosphonate: a report of two cases. AB - In two patients with metastatic disease more lesions were detected on scintigraphs obtained with the 'low uptake' bone-scanning agent dimethyl-amino diphosphonate. The results in these two patients provide practical support for the suggestion that bone-scanning agents with low uptake in normal bone, but high tumour-to-normal bone ratios, will allow better delineation of focal bone abnormalities. PMID- 6240402 TI - Extraosseous 99mTc-MDP uptake in mediastinal thyroid goiter: two case reports. AB - Two cases of retrosternal multinodular goiter are described in which 99mTc-MDP concentrated. The possible etiology of this unexpected finding is briefly discussed in addition to the differentiation from other mediastinal tumors which may potentially accumulate 99mTc-MDP. PMID- 6240403 TI - Neuraminidase deficiency presenting as non-immune hydrops fetalis. AB - A newborn infant with oedema, ascites and hepatosplenomegaly is described. In ascites fluid foamy macrophages were found, in a liver biopsy cytoplasmic inclusions and membrane-bound vacuoles were seen. Furthermore the child excreted excessive amounts of sialic acid-rich oligosaccharides in the urine, and therefore a neurovisceral degenerative disorder was assumed. The diagnosis of sialidosis was confirmed by enzymatic assay in cultured fibroblasts, in which a complete deficiency of the lysosomal enzyme neuraminidase could be demonstrated. After recurrent septicaemias the child became dystrophic and died at the age of 6 months. Our case is compared with sialidosis observed by other authors, the wide phenotypic diversity within this biochemical defect is emphasised. The occurrence of hydrops fetalis in lysosomal storage diseases is discussed. PMID- 6240405 TI - Safety, tolerability and efficacy of PN 200-110, a new calcium antagonist in patients with angina and coronary heart disease. AB - The safety, tolerability and efficacy of PN 200-110, a new calcium antagonist with minimal negative inotropic effects, were studied in twelve patients with stable angina pectoris and coronary artery disease. The study design was single blind and placebo-controlled and increasing doses of the drug were used on consecutive days to investigate a dose response relationship. Eleven patients completed the trial. Response to the drug was evaluated using symptom limited cycle ergometric exercise. PN 200-110 in all three tested doses of 2.5 mg, 5.0 mg and 10.0 mg significantly increased the resting heart rate (p less than 0.02) and the exercise time to the onset of angina pectoris (p less than 0.02). Doses above 2.5 mg did not appear to improve the exercise parameters evaluated. Four patients had side effects probably due to PN 200-110 but these were mild and included dizziness, headache and flushing. There were no abnormal results from haematological and biochemical screening or from urine testing. We conclude that PN 220-110 can be given safely to patients with coronary artery disease without producing deleterious effects on blood pressure either at rest or during exercise. PMID- 6240404 TI - Cyclosporin A in orthotopic porcine liver transplantation. Long-term survival after short-term treatment. AB - The aim of this study was to evaluate the efficacy of cyclosporin A (CyA) in prolonging graft survival after orthotopic porcine liver transplantation in mixed lymphocyte culture (MLC) mismatched couples. CyA was given intramuscularly for a period of 21 days, starting on the day before transplantation. In order to study the fate of the graft, frequent liver biopsies and blood samples were taken after transplantation. 4 pigs received CyA at a dose of 10 mg/kg/day, and 10 animals were treated with 20 mg/kg CyA per day. In the low-dose group 1 pure plasma cellular rejection was noted, while the grafts of 2 pigs showed a transient plasma cellular infiltration in the portal tract. By doubling the dose, only 1 out of 10 animals rejected the liver graft. The livers of the other 9 animals did not show any noteworthy histological sign of rejection, and also the liver function tests were normal. Total serum bile acids and routine liver function tests remained undisturbed in animals that accepted the MLC-mismatched graft and increased in cases of rejection. No nephrotoxicity was noted due to CyA treatment. The main complications encountered were infections leading to death in 4 CyA-treated pigs, while the liver graft was functioning well. Short-term treatment with CyA can overcome the rejection of a MLC-mismatched porcine liver graft and induces a state of long-term acceptance. PMID- 6240406 TI - Long-term suppressor cell lines. I. Demonstration of suppressive function. AB - Suppressor T cell (Ts) lines have been generated and maintained in culture for over one year. Cells from these lines suppress proliferation by primed lymph node cells and antibody production by primed spleen cells. Ts were originally obtained from either spleens of mice rendered tolerant to human gamma globulin (HGG) or short-term cultures of normal spleen cells. Ts from these two sources have previously been shown to exhibit antigen specificity in that only HGG-specific immune responses were suppressed. Prolonged culture of Ts, however, leads to 2 events: an enrichment for suppressive activity in the cultures; and a polyclonal activation of Ts which is demonstrated by the acquired ability of Ts cell lines to regulate responses to antigens other than HGG. Ts cell lines still contain HGG specific Ts which can be isolated by their capacity to bind to HGG-coated plates. Only HGG-specific immune responses are suppressed by the HGG-binding Ts. PMID- 6240408 TI - Protection of the classical and alternative complement pathway C3 convertases, stabilized by nephritic factors, from decay by the human C3b receptor. AB - Formation and function of the classical (C4b,2a) and alternative (C3b,Bb) complement pathway C3 convertases are regulated by the intrinsic lability of the enzymes, extrinsic decay by C4bp and H, cleavage of C4b and C3b by I, and by the inhibitory action of the C3b receptor molecule (CR1). Binding of C4 nephritic factor (C4Nef) to C4b and of C3 nephritic factor (C3Nef) to C3b stabilizes the C3 convertases and bypasses inactivation by C4bp, H and/or I. In the present study, binding of C4Nef to the classical C3 convertase was found to prevent decay of C4b,2a by inputs of CR1 that were at least 15 times the amount of CR1 which inactivated 50% unstabilized classical pathway C3 convertase sites in 2.5 min. CR1 could however inhibit lysis of C4b,2a(C4Nef)-bearing cells in a dose dependent manner. The latter inhibitory effect was directed at the interaction of C5 with the C5 convertase, most likely at C5 binding to cell-bound C3b. In an analogous manner to C4Nef in the classical pathway, stabilization of alternative pathway C3b,Bb convertase sites by C3Nef resulted in a relative protection of C3 convertase sites from decay by CR1. Thus, C4Nef and C3Nef can bypass all mechanisms susceptible to regulate function of the classical and alternative pathway C3 convertases. Because CR1 is essential for degradation of C3b bound to immune complexes in whole blood, stabilization of C4b,2a and C3b,Bb by C4Nef and C3Nef may alter in vivo processing of immune complexes in patients with nephritic factors. PMID- 6240407 TI - Long-term suppressor cell lines. II. Suppressor-target interactions. AB - Long-term nonhybridized murine suppressor T cell (Ts) lines, some of which have been in culture for over one year, are genetically restricted in their ability to suppress proliferation of primed lymph node cells (LNC). The genetic restriction maps to the I region of the major histocompatibility complex and resides in either the I-A, I-E or I-J locus. Suppressive activity is only slightly decreased following irradiation of the Ts with 2000 rds. The target for suppressive activity expressed by Ts cell lines is the helper T cell as suggested by experiments in which LNC proliferation was maximally suppressed when Ts were present early in the assay culture. The identity of the target cell was confirmed by experiments in which Ts were shown to suppress the anti-human gamma globulin plaque-forming cell response resulting from co-culture of primed B cells with cloned human gamma globulin-specific helper T cells. PMID- 6240409 TI - T-lymphocyte subsets in pleural fluids: discrimination according to traditional and monoclonal antibody-defined markers. AB - T-lymphocyte subpopulations in pleural fluid and in peripheral blood from 17 patients admitted for pleural effusion were identified by E-rosette formation and delineated by monoclonal antibodies OKT3 (peripheral T-cells), OKT4 (helper/inducer cells), and OKT8 (suppressor/cytotoxic cells). We studied 13 patients with specified pleural diseases (tuberculosis, malignancies, connective tissue diseases, congestive heart failure) and 4 patients with non-specified pleural diseases. Our findings showed that the percentage of T-cells increases in pleural fluid versus peripheral blood whatever the diagnosis is, and that these T cells are predominantly helper/inducer cells. Moreover, a recently described T lymphocyte subpopulation, which expresses neither T3 nor other monoclonal antibody-defined markers, seems to be concentrated in the pleural fluid, especially in tuberculosis and malignant effusions. Although T-lymphocyte delineation seems to fail to aid in etiological diagnosis of pleurisy, such determinations could provide informations about local pathogenic mechanisms. PMID- 6240410 TI - [Action of a vitamin complex with oxidative-reductive properties on the course of acute myocardial hypoxia and ischemia]. AB - Experiments on mice with simulated isobaric hypoxia and anoxia have demonstrated marked antihypoxic action of a complex of vitamins with electron-acceptor activity (ascorbic acid, riboflavine mononucleotide, lipoic acid, nicotinamide). In dog experiments, the complex of vitamins reduced metabolic acidosis in the ischemia zone as shown by the lactate release test and increased the collateral coronary circulation. The protective action of the drug recorded in hypoxia and regional myocardial ischemia is regarded as linked with the ability of the vitamin complex to raise the conjugation of oxidation and phosphorylation in the mitochondria of a pathologically altered myocardium, as well as with its membrane stabilizing action and inhibition of lipid peroxidation. PMID- 6240411 TI - [Blood acid-base status in the adaption of mono- and dizygotic twins to alpine conditions]. PMID- 6240412 TI - [Genotypic conditionality of the body reaction to autonomotropic agents in normoxia and alpine hypoxia]. PMID- 6240413 TI - [Contractile characteristics of developing fast and slow muscles during colchicine blockade of axoplasmic transport in their nerves]. AB - Within a month after colchicine application to the sciatic nerve of a newborn rat, deviation from the normal development occurred in contractile and histochemical properties of fast (extensor digitorum longus) and slow (soleus) muscles. The data obtained revealed the importance of neurogenic agents of neurotropic control transported from pericarions of motoneurons for differentiating skeletal muscle fibers. PMID- 6240414 TI - [Simultaneous vessel catheterization and placement of the transducer of an electromagnetic flowmeter on the portal vein of the cow]. PMID- 6240415 TI - [Cortical mechanisms of sensorimotor coordination in the cat]. AB - A review of works by fellows of the Lab.of Sensory-motor Systems Physiology of the Ukhtomsky Physiological Institute on neurophysiological investigation into the role of sensory-motor cortex in organization of movements. PMID- 6240416 TI - The effect of idiotype-specific and anti-ACA-1 sera on T cell subpopulations responding to H-2 antigens. AB - A xenogeneic anti-CBA-anti-C57BL/6 idiotype-specific serum reacted specifically only with CBA anti-C57BL/6 T cells. It inhibited T killers, T lymphocytes proliferating in one-way MLC and T cells which take part in the rejection of the cardiac allografts. However, it did not affect T suppressors and T MIF producers. Another antiserum, directed against ACA-1 (activated cell antigen), inhibited T killers of various specificities, but not T suppressors or T MIF producers. These results allow us to suggest that (1) the idiotype-like structures of T suppressors and T MIF producers differ from those of other T cell subpopulations responding to H-2 antigens; (2) ACA-1 is expressed on the surface of T killers, but not on T suppressors or T MIF producers; (3) T cells producing MIF form a separate subpopulation. PMID- 6240417 TI - T helper cell inclusion into the mathematical model of immunological tolerance. AB - The experimentally observed recovery from tolerance to HSA in chickens is much slower than the values calculated by means of the simple mathematical model of B cell tolerance. The model assumes that tolerance is due to elimination or irreversible inactivation of immunocompetent cells reactive to the tolerated antigen, and that the recovery from tolerance is caused by the differentiation of new immunocompetent cells. Even when two collaborating B cell populations reactive to HSA were considered, the calculated recovery from tolerance was much slower than the observed one. Therefore, T helper cell tolerance was suspected and included into the mathematical model. The experimental data agreed best with the calculated values of the recovery from tolerance to HSA obtained with a T cell lifespan of 200 days. On the other hand, when two T helper cell populations cooperated with B cells in anti-HSA antibody production, the curve best fitting the experimental data corresponded to the T cell lifespan of 60 days. PMID- 6240418 TI - [Clinical and controlled evaluation after 2 years of an enamel-dentin adhesive and a microfilled composite in the treatment of cervical lesions]. PMID- 6240419 TI - [Treatment of handicapped children in ambulatory care in North America]. PMID- 6240420 TI - Ontogeny of T-cell mitogen response in Lewis rats: II. Early appearance and loss of suppressor activity. AB - Spleen cells from rats 2 to 132 days old were cultured with 1-125 micrograms/ml Concanavalin A (Con A). At high doses of Con A, the high spontaneous thymidine uptake of spleen cells from rats 15 to 21 days old was suppressed, whereas spleen cells from younger rats showed no suppression of spontaneous mitogenesis at equally high Con A doses. Removal of either plastic-, nylon wool-, or carbonyl iron (cFe) adherent cells not only removed suppression of background by high Con A doses, but also allowed mitogenic responses at adult levels in normally unresponsive 15 to 21 day old pups. Low doses of X-irradiation did not cause a similar loss of suppression. We suggest that although there is an influx of ConA responsive cells into the rat spleens at 15 to 16 days, the mitogen responses of these cells are suppressed by an adherent cell population which is activated by high doses of Con A. PMID- 6240422 TI - Doppler assessment of the fetoplacental circulation in normal and growth-retarded fetuses. AB - The Pulsatility Index (PI) of Doppler flow signals from umbilical arteries was used to study flow resistance of the placental villous circulation. A preliminary reference curve of PI values in normal pregnancy was composed from 23 healthy women examined every 2 wk from the 16th postmenstrual week until delivery. The gestational age-related decrease of PI values reflects a reduction of flow resistance in the placental villous circulation. In small-for-date fetuses significantly increased PI values were found, indicating that this simple technique may permit an early diagnosis of compromised fetoplacental circulation, even several weeks to months before fetal growth retardation is clinically presumed. PMID- 6240421 TI - 2' Deoxycoformycin and human hemopoietic cells in culture. PMID- 6240424 TI - [Mechanism of erythrocyte destruction during immunization]. PMID- 6240423 TI - Biochemical derangements in ischemic myocardium: the role of carnitine. AB - The most important biochemical derangements in ischemic myocardium are the decrease of energy rich phosphates (ATP and phosphocreatine) and intracellular acidosis, both of which contribute to a rapid loss of the contractile function. How and to which extent the alterations of carbohydrate and lipid metabolism are involved in these derangements is briefly discussed. In conditions of oxygen restriction the synchronism between the cytosolic and mitochondrial phase of carbohydrate metabolism is disrupted and beta-oxidation of long chain fatty acids is prevented. Consequently less ATP and more lactate is produced and fatty acids accumulate together with their activation products, acyl CoA in particular. In ischemia free carnitine is also decreased and the carnitine dependent functions (acyl transfer across mitochondrial membrane and pyruvate and alpha ketoglutarate dehydrogenase stimulation) impaired. The meaning of the altered carnitine dependent functions is considered together with the possible (demonstrated and supposed) metabolic effects of carnitine administration in cardiac ischemia. PMID- 6240425 TI - [Population genetic studies of hemoglobinopathies in Uzbekistan. Report 1. Prevalence of hemoglobinopathies in 5 districts of the Uzbek S.S.R]. PMID- 6240427 TI - [Problems in the planning of free blood donation]. PMID- 6240426 TI - ["Rocket" immunoelectrophoresis for identification of Bart's hemoglobin]. PMID- 6240428 TI - Physical assessment of the elderly patient. PMID- 6240429 TI - Musculoskeletal back pain among dentists. PMID- 6240430 TI - Liquid microfills: a solution to Class IV problems. PMID- 6240431 TI - Monoclonal antibody-defined B cell subsets in aging humans and Down's syndrome. AB - Peripheral blood from aging and young humans and patients with Down's syndrome, and from age- and sex-matched controls, was studied for the proportions of surface immunoglobulin (SIg+) bearing and monoclonal antibodies FMC1, and FMC7 defined B lymphocytes and B lymphocyte subsets using fluorescent-activated cell sorter. In aging humans, the proportion of SIg+ and FMC1+ (that detect all B lymphocytes) were comparable to simultaneously studied healthy young controls. However, FMC7+ (that detects a subset of B cells) B cells were significantly (p less than 0.05) increased when compared to young subjects. In aging subjects, the proportions of FMC7+ B cells were comparable to their FMC1+ B cells, whereas in young subjects FMC7+ B cells were a subset of FMC1+ B cells. In Down's syndrome, a phenomenon similar to aging humans was observed, that is the proportions of FMC7+ were increased when compared to age- and sex-matched controls and were comparable to their own FMC1+ B cells. This study demonstrates the abnormality of B lymphocytes in human aging and Down's syndrome. The significance of these findings is discussed. PMID- 6240432 TI - [Radiation doses to the population of the Cheliabinsk region due to roentgenodiagnostic examinations]. PMID- 6240433 TI - [Activities of a coniotuberculosis center]. PMID- 6240434 TI - [Advanced training of factory physicians in the organization and application of therapeutico-preventive measures in occupational hygiene]. PMID- 6240435 TI - [Real and false risks of injectable hormonal contraception]. PMID- 6240436 TI - Ultrasonic screening in predicting the time of ovulation. AB - A consistent sign of imminent ovulation in the graafian follicle has been observed by ultrasonic screening. The sign is the appearance of a double contour along the follicle wall, with the wall losing its clear appearance. This is an important sign which can be used in all programs in which the exact timing of ovulation is important, in order to receive the best possible results in treatment of infertility. PMID- 6240437 TI - Ruptured berry aneurysms: a clinical, pathological and forensic review. AB - A retrospective autopsy survey of 583 cases of ruptured berry aneurysm over a period of 25 years with reference to incidence, circumstances and predisposing factors. Over half of the deaths occurred in the 50-80 year age group, the overall male/female ratio being 2:3, the aneurysms being predominately on the middle and anterior cerebral arteries. Most deaths occurred in the home environment without precipitating factors, one fifth being sudden and unexpected in nature. There was no connection between physical trauma and ruptured aneurysm and no instance of a criminal or civil charge. Autopsy and dissection of the cerebral vessels is vital to diagnosis, particularly when deaths are unexpected in nature. PMID- 6240438 TI - [Prevention of perinatal transmission of hepatitis B virus infection by HB-Ig and HB-vaccine]. PMID- 6240439 TI - Protein kinase C, a coupling element between stimulus and secretion of basophils. AB - Protein kinase C plays a crucial role in the transmission and control of secretory cell membranal signals. This Ca2+ and phospholipid dependent kinase have been isolated and partially purified from histamine secreting rat basophilic leukemia cells (RBL-2H3 line). The tumor promoter 12-O-tetradecanoyl phorbol-13 acetate ester (TPA) directly activated this isolated enzyme. In the intact RBL 2H3 cells, TPA did not significantly affect free intracellular Ca2+ ions concentration or induce secretion. However, at low concentrations it synergistically enhanced secretion induced either by antigen or ionophore. Significantly, at TPA concentrations exceeding 25 ng/ml both the increase in cytosolic free Ca2+ and the ensuing degranulation were inhibited. The synergism between TPA and the ionophore reaches saturation. These findings suggest that free cytosolic Ca2+ and kinase C-mediated protein phosphorylation are synergistically involved in the mediation of the cellular response. Moreover, kinase C appears to play a dual role both in the activation and termination of secretion. The latter is most probably achieved by closure of the Ca2+ channels in the cells. PMID- 6240440 TI - Lymphocyte subpopulations in chronic Chagas' disease. AB - Monoclonal antibodies of the Orthoclone series were used to identify total T lymphocytes (OKT3) and their helper-inducer (OKT4) and cytotoxic-suppressor (OKT8) subsets in 25 patients with chronic Chagas' disease and 25 healthy controls. No significant difference in the number of total T cells (OKT3+) circulating in the peripheral blood of patients and controls was found. However, in contrast to normal subjects, chagasic patients show quantitative alterations in both helper (OKT4+) and suppressor (OKT8+) T cell subsets. The chagasic patients have abnormal helper/suppressor ratios, with low and high values scattered around the mean. Surprisingly, high ratios were found within females while almost all males have low ratio values. These findings suggest that the putative immunoregulatory disfunctions in patients with chronic chagasic cardiomyopathy may involve both helper and suppressor T cell subsets. PMID- 6240441 TI - Response of rat soleus muscle to tenotomy: a correlative histochemical and biochemical study. PMID- 6240442 TI - Contribution of vasopressin and the sympathetic nervous system in the early phase of high sodium one-kidney renal hypertension. AB - This study assessed the contributions of the sympathetic nervous system and arginine vasopressin to the onset of one-kidney, one-wrap (1K1W) renal hypertension in rats fed a high sodium diet. Two weeks before renal wrap or sham wrap, rats were given a high sodium diet and water ad libitum. At 3 days postwrap, resting mean arterial pressure (MAP) was significantly greater in renal wrapped rats. The contributions of the sympathetic nervous system and vasopressin to blood pressure (BP) were assessed by ganglionic blockade and vascular vasopressin receptor antagonism, respectively. Depressor responses to ganglionic blockade were significantly greater in the normotensive rats as compared to the hypertensive rats. Administration of vasopressin antagonist caused a significant fall in pressure only in wrapped rats. In addition, enhanced pressor responses to bolus injections of vasopressin were observed in hypertensive rats. These results indicate that during this phase of the hypertension there is an activation of the vasopressin pressor system without an increase in neurogenic function. Equalization of arterial pressure occurred only when both systems were blocked, regardless of the order of blockade, which indicated that the sympathetic nervous system and vasopressin interact to maintain the hypertension. Comparison of depressor responses to the blocking agents revealed that the interaction is compensatory in nature since the contributions of the sympathetic nervous system and vasopressin to the maintenance of arterial pressure were greater when the other system was blocked. PMID- 6240443 TI - Brief historical background and principal nature of process. AB - After a brief outline of the historical background, the biological principle of structural tissue adaptation to alterations in load is discussed with special reference to the cardiovascular system. It is stressed that adaptive changes of cardiac and vascular design to local load are rapid, precise, and, on the local level, highly appropriate. However, in hypertension, when they affect the entire systemic resistance section (structural autoregulation), as well as some major "barostats," an upward structural resetting of the entire pressure equilibrium occurs. Further, by way of the consequent vascular resistance vessel hyperreactivity, a positive feedback interaction is established with functional pressure effects and thus tends to further escalate the pressure rise. For these reasons the "normal" structural factor becomes of key importance for the initiation, maintenance, and gradual aggravation of chronic high pressure states. PMID- 6240444 TI - Structural adaptation in borderline hypertension. AB - Animal studies have shown that the cardiovascular system adapts to blood pressure elevation very early in the development of hypertensive disease. This discussion is concerned with structural adaptation in mild or borderline hypertension in humans. A literature review is given, followed by some preliminary data from a current hemodynamic follow-up study on young individuals with mild blood pressure elevation. Hand blood flow at maximal vasodilatation was studied plethysmographically, the baroreceptor reactivity was investigated by analyzing heart rate after intravenously administered angiotensin, and the left ventricle wall thickness was evaluated with M-mode echocardiography. The results indicate that the resistance vessels, the high-pressure baroreceptors, and the left ventricle of the heart are structurally modified even in very mild blood pressure elevation. PMID- 6240445 TI - Circulatory changes in muscle and skin arteries in primary hypertension. AB - This review deals with circulatory adjustments occurring in the limb arteries of hypertensive patients. Measurements of regional blood flow are mandatory, because conclusions drawn from calculated total peripheral resistance often are not applicable to local vascular beds. Limb arteries, which can be followed by easy and noninvasive methods, often are the first choice for study of regional circulation. In this discussion, a few historic studies are cited first; next, the data available on skeletal muscle (forearm and calf) and skin (finger) circulation are reviewed, to show that flow through both muscle and skin is increased in mild and moderate hypertension, while there is a trend to lower values in more severe hypertension. Our own data are derived from 51 untreated patients showing mild to moderate hypertension, matched to 23 normotensive subjects. Flow is measured simultaneously with an ECG-triggered venous occlusion plethysmograph at calf and finger. At rest, calf and finger blood flows are significantly higher and calculated resistance is lower in hypertensive subjects; during reactive hyperemia, blood flow remains higher in hypertensive subjects but calculated resistance increases up to values that are higher, compared to normotensive control subjects; these data are compatible with structural changes in the vascular wall. PMID- 6240446 TI - Regression of structural cardiovascular changes by antihypertensive therapy. AB - Left ventricular (LV) hypertrophy is the structural adaptation of the heart in response to chronic LV pressure load. Studies in spontaneously hypertensive rats (SHR), which represent a model of genetically determined arterial hypertension, reveal that cardiac hypertrophy can be controlled by long-term blood pressure normalization with the use of various antihypertensive agents, such as arterial vasodilatators (hydralazine), converting enzyme inhibitors (captopril), beta receptor blockers (metoprolol), antiadrenergic substances (alpha-methyldopa, guanethidine), and calcium antagonists (nifedipine, felodipine). Additional drug specific effects modulate the mechanical effect of LV systolic unloading on cardiac hypertrophy: after a combined treatment with metoprolol and hydralazine, LV hypertrophy was quantitatively lower than after single hydralazine therapy, although blood pressure had been lowered to the same extent. LV collagen concentration remained unchanged when medical treatment prevented the development of myocardial hypertrophy. However, when therapy was begun after hypertrophy had been completely established, reversal of hypertrophy was associated with an increased LV collagen concentration. In concentric LV hypertrophy with normal systolic wall stress, LV function was not impaired. Consequently, antihypertensive therapy could not improve LV function in this condition. However, in the case of LV dilatation with increased systolic wall stress, LV systolic unloading by antihypertensive therapy could considerably improve LV pumping function. Preventive studies reveal that chronic blood pressure control can prevent cardiac dysfunction in SHR, as frequently is seen in the later phase of untreated arterial hypertension in humans. PMID- 6240447 TI - Reversal of cardiac hypertrophy in humans. AB - Reversal of left ventricular (LV) hypertrophy has definitely been proved to follow effective blood pressure control in hypertensive patients. This reduction in cardiac mass does not depend solely on blood pressure levels as measured in routine follow-up; it varies markedly with the type of drug used and even among patients treated with the same antihypertensive agent. The factors influencing the degree of regression of hypertrophy include stability of blood pressure control (entailing diurnal variations and response to stress), neurohumoral disturbances or fluid retention induced by the antihypertensive drug, and the presence of associated cardiac disease, as well as individual variations such as genetic background and possibly age. LV performance at rest was not depressed by the reduction in cardiac mass but remained normal in relation to changes in LV end-systolic stress. PMID- 6240448 TI - Regression of cardiovascular structural changes by antihypertensive treatment. Functional consequences and time course of reversal as judged from clinical studies. AB - Echocardiographic studies have shown a decrease in left ventricular (LV) wall thickness and an improvement in LV function during antihypertensive treatment. A reduction in LV mass parallels the reduction in LV wall thickness during the first year of antihypertensive treatment, but thereafter favorable changes in LV wall thickness, cardiac output, and total peripheral resistance may be recorded in spite of a constant LV mass. The reason for this is that LV mass is defined by LV wall thickness and LV end-diastolic diameter, and that LV mass may stay unchanged if LV wall thickness decreases when LV diameter increases. This pattern of change is to be expected since LV distensibility and, hence, LV end-diastolic diameter may increase when LV wall thickness decreases. The effect of treatment may thus be divided into two main phases--an initial phase with a reduction in LV mass and a reduction in cardiac output and no change in total peripheral resistance--and a second phase with a constant LV mass but an increase in cardiac output to the pretreatment level again and a concomitant decrease in total peripheral resistance. The increase in stroke volume and cardiac output during this second phase of treatment is mainly dependent on an increase in end diastolic volume, most likely explained by improved LV compliance when LV wall thickness decreases. The concomitant decrease in total peripheral resistance is mainly explained by reversal of structural vascular changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 6240449 TI - Early versus late onset of therapy. Experiences from animal studies. AB - Established primary hypertension is characterized by an "upward structural resetting," that encompasses all pressure-exposed cardiovascular sections. This also affects several of the dominating barostat mechanisms, such as those based on the cardiovascular baroreceptors and volume receptors and on the renal excretory function. One major long-term goal in antihypertensive treatment, therefore, is to achieve reversal and, if possible, normalization of this structural resetting, the more so because such reversal would also interrupt the positive feedback interaction with functional excitatory mechanisms. It is, however, very difficult to analyze precisely the rate and extent of structural cardiovascular reversal in humans, and also whether some antihypertensive drugs are in these respects more efficient than others. In this respect, model therapy studies in rat primary hypertension offer several advantages, thanks to the greatly compressed time scale, uniform material, and easily controlled conditions. This facilitates the elucidation of such important problems as the relative merits of early versus late treatment and optimal duration and intensity of treatment, as well as which drug actions are most efficient in normalizing cardiovascular design. The relatively few rat model studies of structural cardiovascular reversal so far performed are outlined briefly. It is concluded that extended studies along these lines would be of great value in clarifying some general principles of antihypertensive treatment that are also likely to be relevant to primary hypertension in humans. PMID- 6240450 TI - Humoral trophic influence on cardiovascular structural changes in hypertension. AB - Since the early development of structural cardiovascular change in spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP) indicated the involvement of non-pressure-dependent factors in this process in hypertension, smooth muscle cells (SMC) from the aorta of SHR, SHRSP, and normotensive Wistar-Kyoto rats (WKY) were investigated under tissue culture conditions free from blood pressure and humoral factors in vivo. By the observation of such factors as growth rate and DNA or protein synthesis vascular SMC from these rats with genetic hypertension were proved to have intrinsically greater growth activity independently of blood pressure. Although serum from SHR and SHRSP had no specific stimulative effect on SMC growth, circulating epinephrine may accelerate cardiovascular structural changes because isoproterenol added to the culture media enhanced ornithine decarboxylase (ODC) activity. Moreover, SMC from SHR and SHRSP showed greater thymidine incorporation than those from WKY even in response to lower extracellular Na+ concentration. Local nutritional conditions of SMC, which were proved to have a great effect on the morphology and structure of cultured SMC, may be a basic determinant of the development of hypertension induced structural vascular changes or lesions. PMID- 6240451 TI - Myocardial cell hypertrophy or hyperplasia. AB - Growth of the vertebrate heart during embryonic and fetal life is characterized by hyperplasia of myocardial cells; these cells increase in number to a value characteristic for each species. Shortly after birth myocardial cells lose the capability of dividing, and further growth of the heart is due to myocardial cell hypertrophy and nonmuscle cell hyperplasia. This process, which is referred to as hypertrophic growth, results in a 30- to 40-fold increase in volume of individual myocardial cells during normal postnatal growth and maturation. The transition from hyperplastic to hypertrophic growth is related to formation of binucleated myocardial cells as a result of karyokinesis without cytokinesis. The molecular mechanism of this transition is uncertain. The response of the heart to increased metabolic demands or to an increased workload depends on the age of the animal at the time the stress is imposed. Increased myocardial workloads due to systemic hypertension, chronic hypoxia, or carbon monoxide exposure in fetal or early neonatal life lead to cardiac enlargement by causing an increased rate of hyperplasia of myocardial cells or continuation of hyperplasia beyond the normal period of hyperplastic growth. In contrast, imposition of increased loads on the hearts of older animals results in cardiac hypertrophy due to enlargement of myocardial cells and hyperplasia of nonmuscular components. In addition to cellular enlargement, structural remodeling of the myocardial cells, including alterations in the relative proportions of cellular organelles and in the ultrastructure of individual organelles, occurs during the development of hypertrophy in the adult heart.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 6240452 TI - Functional dynamics of the left ventricle in hypertensive hypertrophy and failure. AB - In essential hypertension ventricular function is determined primarily by the degree of hypertrophy (myocardial factor) and by the organic complications in the coronary artery (coronary factor). Ventricular function is inversely correlated with ventricular size and systolic wall stress, inasmuch as ventricular function diminishes when these two variables increase. Even the young hypertensive heart of normal size with no angiographic abnormalities appears to be prone to ischemia, because the coronary reserve is seriously limited even in the absence of coronary stenosis. Unlike ventricular distensibility, myocardial compliance may be normal even in the presence of pronounced myocardial hypertrophy. As myocardial compliance decreases, systolic wall stress increases and ventricular function is reduced. The hypertensive heart, the most common form of an irregular hypertrophy of the ventricular wall, is found in 14% of such cases. Analysis of the degree of hypertrophy shows that the hypertrophy can be inappropriately high (high mass-to-volume ratio, reduced wall stress), appropriate, or inappropriately low (normal mass-to-volume ratio, increased wall stress). Digitalis glycosides, together with antihypertensive measures, are indicated for the dilated hypertensive heart; beta-receptor blockers are sound medication for the compensated hypertensive heart both with and without coronary stenoses. The following discussion includes classification of hypertensive heart disease based on the cardiac complications following hypertension. PMID- 6240453 TI - Synthesis of collagen in cardiac and vascular walls. AB - Collagen synthesis and content have been shown to be elevated in the arterial wall and heart of hypertensive animals. These increases in collagen synthesis and content have been implicated in the maintenance of raised blood pressure. Inhibitors of collagen synthesis, beta APN and 3,4-dihydroproline, were shown to delay the onset of hypertension and reverse established hypertension. Therapeutic intervention with antihypertensive drugs resulted in a decrease in arterial collagen synthesis and a reversal of cardiac hypertrophy. In some instances (i.e., DOCA-salt), chronic administration of antihypertensive drugs caused a restructuring of the arterial wall and resulted in an apparent remission of the hypertensive disease. PMID- 6240454 TI - The inhomogeneity and appropriateness of the myocardial response to stress. AB - Myocardial hypertrophy, with high morbidity and mortality, is a natural outcome of hypertensive heart disease. The increase in myocardial mass is associated with a cellular and subcellular reorganization of the myocytes. The following study uses rapid myothermal techniques to assess the contribution of the major intracellular changes to the adaptive hypertrophic process in various heart models. Pressure overload and thyrotoxic hypertrophy were produced in the rabbit. In the rat, hypertrophy was produced by constricting the renal artery (Goldblatt hypertensive rat) or by using the spontaneously hypertensive rat strain. Atrophy was produced by administration of propylthiouracil in the drinking water. The V1/V3 myosin isoenzyme ratio was decreased in the pressure overload, Goldblatt, and propylthiouracil animals. This was associated with a decrease in total activity-related heat, initial heat, and tension-dependent heat per tension time integral. The tension-independent heat was decreased in the pressure overload, while the time to peak tension was increased. The economy of the metabolic recovery process was unchanged in the pressure overload and Goldblatt preparations. In the propylthiouracil preparation the recovery processes became uneconomical. The spontaneously hypertensive rat exhibited mild cardiac hypertrophy but in all other respects the heart was unchanged from the normal animals. The thyrotoxic hearts had a high V1/V3 myosin isoenzyme ratio, which was associated with a high total activity-related heat, initial heat, and tension dependent heat per tension time integral. The tension-independent heat was reduced in the thyrotoxic preparations. The appropriateness of each of the intracellular changes is evaluated in terms of the demands made on the heart. PMID- 6240455 TI - Functional consequences of structural adaptation of the heart in hypertension. AB - Extent of myocardial shortening is inversely related to afterload. Maintenance of normal stroke volume (SV) in hypertension will therefore require elevation of cardiac performance. The question of whether left ventricular hypertrophy, which develops during chronic hypertension, enhances or depresses cardiac function has been examined experimentally. Cardiac function curves have been constructed and maximal cardiac output has been determined during rapid volume load in intact animals or in isolated perfused hearts from spontaneously hypertensive rats (SHR) and from normotensive rats. When preload, afterload, heart rate, and contractility are controlled, maximal performance is enhanced in the SHR heart, and its ability to increase contractility on elevations in afterload (homeometric autoregulation) is reset in proportion to the increase in arterial blood pressure. Although a reduced volume compliance of the SHR left ventricle has not been documented, its diastolic properties will still be influenced by the increased wall thickness. The reason is that a higher pressure is required to induce a given diastolic wall stress when wall thickness/radius ratio is increased according to Laplace's law. Since wall stress in turn determines the extent of myocardial shortening, maintenance of normal stroke volume in SHR calls for increased diastolic pressures or increased inotropic stimulation. The structural adaptation of the heart to hypertension will thus enhance its systolic performance, but will influence its diastolic properties so that secondary adjustments are required to enhance ventricular filling or the inotropic state of the heart, or both. PMID- 6240456 TI - The coronary circulation in hypertensive heart disease. AB - This study analyzes and compares systemic and coronary hemodynamics in patients with essential hypertension in relation to hypertrophic heart disease of nonhypertensive origin. Left ventricular function (as assessed from the cardiac index, stroke volume index, ejection fraction, mean velocity of circumferential fiber shortening, mean normalized systolic ejection rate, and isovolumic indexes) may be normal in patients with hypertensive hypertrophy, even with a large increase in muscle mass and in the presence of concomitant coronary artery disease. Left ventricular function is impaired when regional contraction abnormalities or ventricular dilatation, or both, occur and is inversely related to both cardiac size and systolic wall stress. Coronary blood flow (+ 18%), coronary resistance (+ 38%), and myocardial oxygen consumption (MVO2) (+ 21%) are increased in essential hypertension. Coronary reserve is reduced even in hypertensive hypertrophy without evidence of coronary artery disease. MVO2 per mass unit was directly correlated with systolic wall stress per cross-sectional area of the left ventricular wall. Coronary reserve may remain normal in both moderate and excessive hypertrophy, provided systolic wall stress and hence the myocardial oxygen consumption are not increased. It is concluded that the appropriateness of left ventricular hypertrophy, as a result of mass-to-volume ratio and stress, is a major determinant of left ventricular performance, of coronary blood flow, and of myocardial oxygen consumption. PMID- 6240457 TI - Influence of ambient temperature and drug treatments on brain oedema induced by impact injury on skull in rats. AB - The progression and persistence of oedema development following impact-injury on closed skull was studied in anaesthetised as well as in unanaesthetised rats. The degree and rate of oedema development, following trauma, was aggravated in anaesthetised hypothermic animals but was reduced/or delayed by maintenance of body temperature at euthermic level. In general, the unanaesthetised animals showed a greater accumulation of oedema fluid than the corresponding anaesthetised group. The development of oedema corresponded more or less with the accumulation of 5-HT level in plasma and brain. This development of oedema was completely prevented following pretreatment with p-CPA, indomethacin paracetamol and aminophylline in unanaesthetised animals; whereas these drugs were able only to partially reduce the oedema development in euthermic anaesthetised animals. On the other hand the cyproheptadine pretreatment aggravated the oedema development which was more pronounced in unanaesthetised animals. The probable mechanism of the action of these drugs has been discussed. PMID- 6240458 TI - Effects of some drugs on islet function in catfish. AB - Blood glucose variations and concomitant bioptical cytopathological changes in the pancreatic islets following treatment with certain drugs were studied in the catfish. Glucose loading produced a dose-related hyperglycemia, maximum within 3 hr, while alloxan caused a biphasic rise in glucose level without induction of permanent diabetes. Streptozotocin elicited a monophasic hyperglycemic state at a lower dose and biphasic response at higher doses. Glybenclamide produced hypoglycemia in normal and sham-operated fish; the depancreatized animals were unresponsive to this treatment. In all the cases, normoglycemic values were restituted within 4 days of the treatment. The beta-cells of the islets underwent varying histopathological changes with signs of regenerative activity. A depletion in heavy metal (zinc) in these cells was also evident after treatment with streptozotocin. PMID- 6240459 TI - Comparative effects of etodolac, indomethacin, and benoxaprofen on icosanoid biosynthesis. AB - Etodolac (Ultradol) is a new tetrahydropyrano-indole derivative which has shown pronounced analgesic and antiinflammatory properties. Its effects on the different pathways of metabolism of arachidonic acid have been studied and compared to the effects of indomethacin and benoxaprofen. All three drugs tested inhibited the cyclooxygenase activity of the parenchyma as assessed by inhibition of LTB4- and LTD4-induced contraction. However, the activity of human polymorphonuclear leukocyte 5-lipoxygenase and of human platelet 12-lipoxygenase was inhibited only by very high concentrations (1 X 10(-4) M and over) of these compounds, whereas nordihydroguaiaretic acid (NDGA) was active at concentrations 100 times lower. In the Schultz-Dale reaction of the guinea pig trachea, etodolac, benoxaprofen, and indomethacin produced increases of the myotropic contractile activity of the tissues sensitized to ovalbumin. Our results do not lend support to the hypothesis that the mechanism of action of these antiinflammatory drugs is linked to the inhibition of lipoxygenases. PMID- 6240461 TI - The elderly are at risk. PMID- 6240460 TI - Deficiency in C3b receptors on neutrophils of patients with chronic granulomatous disease and hyperimmunoglobulin-E recurrent infection (Job's) syndrome. AB - C3b receptor (CR1) expression by neutrophils (PMNs) and erythrocytes (Es) from patients with chronic granulomatous disease (CGD) or with hyper-IgE, frequent infection (Job's) syndrome was compared with that of control subjects. The control subjects consisted of one group of patients with infections and a second group of normal, healthy individuals. Three quantitative assays were used: rosette formation with C3b-coated cellular intermediates (EAC43b), binding of radiolabeled monoclonal anti-CR1 ([125I]anti-CR1) to PMN surfaces, and binding of the antibody to nonidet P-40 (NP-40) extracts of PMNs and Es in an immunoradiometric assay. Rosette formation by the PMNs of five male CGD patients was about 50% of that of paired normal control subjects, whereas the rosette formation of three female CGD patients was similar to that of the control subjects. Surface binding of [125I]anti-CR1 to PMNs of 10 CGD patients was about half that of the normal subjects (mean percent binding was 2.33% for the CGD patients vs. 3.86% for the normal subjects, giving a difference of -1.53 +/- 0.22%, P less than 0.001 by the paired-sample t test). The degree of PMN binding was similarly low for both the male and the female CGD patients. Conversely, the binding of anti-CR1 to the PMNs of 11 infected control patients appeared to be similar to that of the normal subjects (4.51% for the patient vs. 4.21% for the paired normal subjects). The infected control group originally included four Job's syndrome patients, and when this subgroup was analyzed separately, their PMNs were shown to bind significantly less anti-CR1 than did the PMNs of the normal subjects (P less than 0.01 by the paired-sample t test). In contrast, the other infected control patients showed higher-than-normal levels of anti-CR1 binding (P less than 0.05). When compared to that of the normal subjects, the total CR1 quantitated in PMN extracts was also lower than normal in CGD patients (P less than 0.01 and in the PMN extracts of eight Job's syndrome patients tested (P less than 0.01). The PMNs of the other infected control subjects were not significantly different from those of the normal subjects in total CR1 expression. Extracts of Es from Job's syndrome patients also had fewer than normal CR1 (P less than 0.02). On the other hand, CR1 levels in E extracts from the CGD patients and the other control patients were similar to those in the normal control subjects. Quantitations of C3, C4, and factor B were normal in CGD.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 6240462 TI - Hospitals and the provision of care to the aged: a cluster analysis. AB - As the American population ages, the hospital industry will undergo substantial restructuring to meet the increased demand for geriatric and long-term care services. Understanding this important trend, however, has been inhibited by limited research and the vast range of services that currently exists. This investigation develops empirically a classification schema of hospitals that reflects the mix of geriatric services they provide. The study also identifies the organizational and environmental characteristics of hospitals providing these geriatric service categories. Factor analysis, clustering, and analysis of variance were performed on a sample of 416 hospitals. Seven distinct groupings of hospitals that differed systematically on geriatric service mix and other contextual factors were identified. PMID- 6240463 TI - Medical expenditures of terminal cancer patients during the last year of life. AB - To measure the patterns of medical expenditures under conventional modes of cancer care for the terminally ill, we examined Blue Cross and Blue Shield Plan claims records for care during the 12 months preceding the deaths of 1,054 nonelderly patients diagnosed as having breast, colon-rectal, or lung cancer. Expenditures averaged +21,219 for the terminal year and grew exponentially as death approached, with +6,161 (29%) being spent in the final month alone. We found very few significant differences in spending or utilization by diagnosis, age, or sex of the terminal patient, but sizable differences by state of residence and between nonmetropolitan and metropolitan area residents. Our findings represent a baseline against which experience under new hospital payment strategies and alternative delivery systems might be compared. PMID- 6240464 TI - Utilization and charges for terminal cancer patients in Rhode Island. AB - A population-based sample of 2,104 terminal cancer patients who died in Rhode Island during 1980-1981 was created by merging death certificates, the claims of Medicare and non-Medicare health insurance beneficiaries served by Blue Cross and Blue Shield of Rhode Island, and records of the state's only hospice. The data collected included utilization and charges for services rendered by hospitals, nursing homes, home health agencies, physicians, and outpatient clinics. Regression analysis of charges during the last month and six months revealed significant differences for age and hospice: Six-month charges were found to be inversely related to age (+151 for each year of age), and the charges for the last month of care for decedents who received hospice care were 43.5% lower than the charges for conventional care. PMID- 6240465 TI - An evaluation of hospices in the New York State Hospice Demonstration Program. AB - In response to a New York State legislative directive, the study reported herein was undertaken to evaluate the use of hospice care within the state's Hospice Demonstration Program. Twelve hospice programs, each providing one of three different models of hospice care, were studied. The community-based programs were found to be considerably less costly than both the hospital-based scattered-bed programs and the hospital-based autonomous-unit programs. The costs of all three programs, however, were less than the costs of conventional terminal care. Although satisfaction with all three models was high, it was higher for both kinds of hospital-based programs than for the community-based programs. PMID- 6240466 TI - Health insurance under competition: would people choose what is expected? AB - To determine relative preferences for different cost-sharing options, we asked a 17% random sample of 2,754 nonunion employees to compare health insurance policies that differed in the level of 1) deductible amount, 2) coinsurance rate, 3) coinsurance limit, 4) maximum liability, and 5) price. Using conjoint analysis, we derived preference curves for each of the five components and measured preferences for the compromise between more coverage and the corresponding price increase. In contrast to other studies, our findings suggest that under fair market prices, respondents would choose policies with greater coverage for catastrophic illness, and they would as likely choose cost-sharing policies that contain incentives to reduce utilization as they would choose policies without these incentives. PMID- 6240467 TI - Why do women physicians work fewer hours than men physicians? AB - Because of the large public investment in medical education, it is important to understand why women physicians work significantly less than men physicians. National survey data on office-based private practice physicians were used to estimate (using two-stage least squares technique) hours and weeks worked for men and women physicians separately. Contrary to conventional wisdom, shorter work weeks for women physicians are not the result of child care responsibilities. Nor would higher earnings encourage women physicians to work longer hours. Instead, we found significant work reductions among married women physicians (but not men), implying subordination of careers by women where combined family incomes are high. PMID- 6240468 TI - An analysis of hospital case mix, cost, and payment differences for Medicare, Medicaid, and Blue Cross Plan patients using DRGs. AB - To increase our understanding of case mix as a major contributor to variability in hospital costs, we examined the relationship among case mix, resource consumption, and payments for all Medicare, Medicaid, and Blue Cross Plan patients discharged from 28 hospitals in New York State. Case mix differences among the three payers were found to contribute to differences in overall average cost per case, although residual differences in costs existed at the DRG level. Medicare and Medicaid payments more often covered the actual costs of their patients than did Blue Cross Plan payments. Our results indicate the importance of payer-specific data in the design of effective and equitable reimbursement and cost containment strategies. PMID- 6240469 TI - Differences in the direct costs of public and private acute inpatient psychiatric services. AB - This exploratory study examined differences in the direct costs of acute inpatient psychiatric services in seven public county-operated specialty hospital units and six private community general hospital units in Wisconsin. There were no significant or substantial differences in measures of severity of patients between the public and private systems. Direct costs per stay and per day were significantly lower in the private units, although charges may have been higher in the private units. These differences in costs appear to be the result of private units having a significantly higher average daily census, more goal emphasis for cost containment, and more psychiatrist influence on how the unit was run. Our findings suggest that mental health system managers examine opportunities for achieving economies of scale and that they set and manage goals for efficiency. PMID- 6240470 TI - Experiences on the efficacy and safety of nalidixic acid, oxolinic acid, cinoxacin and norfloxacin in the treatment of urinary tract infections (UTI). AB - The purpose of this study was to determine the effectiveness and tolerability of norfloxacin, cinoxacin and oxolinic acid in the treatment of urinary tract infections (UTI) in comparison to nalidixic acid. 125 patients were given the drugs in the appropriate doses for 10-14 days and 30 patients were treated for six weeks. Clinical, bacteriological, hematological and chemical checks were made on all patients before and after treatment. It was found that norfloxacin, cinoxacin and oxolinic acid are safe and effective against Escherichia coli, Klebsiella and Proteus, the commonly encountered organisms in urinary tract infections. The cure rate for norfloxacin was 93%, for cinoxacin 83%, for oxolinic acid 80% and for nalidixic acid 70% in the short course. However, these differences were not statistically significant. Oxolinic acid, cinoxacin and norfloxacin have the advantage over nalidixic acid of being administered only twice daily. PMID- 6240471 TI - The skin and diabetes mellitus. PMID- 6240472 TI - Fixed drug eruptions. A study of 20 occurrences in Singapore. AB - Twenty occurrences of fixed drug eruptions (FDE) were studied. Of these, 12 were due to tetracyclines and 4 were due to analgesics (3 from pyrazolone derivatives and 1 from acetylsalicylic acid). Sixteen of the patients had less than 10 lesions each. The lips were affected in eight instances, and therefore seem preferentially involved. At presentation, seven patients were unaware of a drug relationship to their condition. A comparison of six reported series (including this one) revealed that the causative drugs varied over the years 1956-1983 as well as by region. PMID- 6240473 TI - World-wide control of hepatitis B. PMID- 6240474 TI - An epidemiological study of Hirschsprung's disease. AB - All newly diagnosed cases of Hirschsprung's Disease among children born in Baltimore City and County, Maryland and diagnosed within the Baltimore Standard Metropolitan Area during 1969 through 1977 were identified. Using hospital records and death certificates, 33 cases were ascertained. An overall incidence rate of 18.6 per 100 000 livebirths was found, similar to that reported by others. A high male to female ratio (4.32:1) was found; the ratio for non-whites to whites was 1.67:1. Non-white males had the highest rate, 37.6 per 100 000 livebirths. These findings plus the fact that 9% of these children were also diagnosed as having Down's Syndrome, were evidence that the aetiology of Hirschsprung's Disease may be partially genetic. Among environmental factors studied, there was no time trend and no relationship with socioeconomic status found. Among whites, there was a larger percentage of children who were the first births of mothers aged 30 and above, a result previously reported for children with neural tube defects. Very little is known about micro-environmental factors in relation to Hirschsprung's Disease and this would seem to be the area for future emphasis in research. PMID- 6240475 TI - [Thrombolytic therapy of acute heart infarct]. PMID- 6240476 TI - Liquid crystal contact thermography in the clinical evaluation of traumatic low back pain. PMID- 6240477 TI - Lack of effect of exercise on platelet activation and platelet reactivity. AB - The effects of brief maximal exertion on platelet activation and reactivity have been studied in normal subjects. Although initial studies in seven subjects showed apparent exercise-induced platelet activation and enhanced platelet reactivity, these findings could not be confirmed in 13 subjects studied subsequently. There was no change in the platelet aggregate ratio, platelet fluorescent granule number or the plasma platelet factor 4 (PF4) or beta thromboglobulin, although transient and significant increases in the platelet count and plasma heparin neutralizing activity (HNA) occurred. These results were reproducible in subjects studied more than once. It is postulated that in vitro platelet activation, most likely associated with blood collection, explained the initial results. It is concluded from the subsequent studies that in normal subjects brief maximal exercise causes neither platelet activation nor altered platelet reactivity but does cause a transient increase in the platelet count. The increase in HNA with exertion, without any accompanying increase in the PF4, demonstrates that these assays measure different substances and that the increase in HNA following exertion is most unlikely to be derived from platelets. PMID- 6240478 TI - Muscle glycogen repletion after exercise in trained normal and diabetic rats. AB - We hypothesize that training results in a faster and greater repletion of glycogen in skeletal muscles of normal and diabetic rats. Normal male Sprague Dawley rats (100-140 g) were divided into two groups--one to train by treadmill running for 10 wk and the other to remain sedentary. Forty-eight hours after the last training session the rats of both groups were exercised to exhaustion. One subgroup of each was fed oral glucose (3 g/kg) at exhaustion and killed 60 min later. The other was killed at exhaustion. The glycogen concentration of soleus, plantaris, and red and white gastrocnemius was determined in all rats. The trained group had higher glycogen levels after glucose feeding in all muscles (P less than 0.002) and repleted their muscle glycogen more rapidly (P less than 0.05). However, in diabetic rats (45 mg streptozotocin/kg body wt) the trained and sedentary rats have similar glycogen levels and glycogen repletion rates in all muscles. Compared with the normal trained rats, the diabetic trained rats had slower glycogen repletion rates (P less than 0.05). PMID- 6240479 TI - Yersinia enterocolitica infection-vagaries. PMID- 6240480 TI - Review and update on open fractures. PMID- 6240481 TI - Cancer prevention and public health. PMID- 6240482 TI - The neurocutaneous syndromes: diagnosis and management for the primary care pediatrician. PMID- 6240483 TI - Intraoperative assessment of aortoiliac stenosis: role of papaverine-induced hyperemia. PMID- 6240484 TI - Arkansas Medical Society Membership Roster December 1, 1984. PMID- 6240485 TI - Chemical confirmatory tests for ochratoxin A, citrinin, penicillic acid, sterigmatocystin, and zearalenone performed directly on thin layer chromatographic plates. AB - Published tests have been improved and a new procedure is described for chemical confirmation of mycotoxins directly on thin layer plates. After extraction and preliminary cleanup chromatography with n-hexane or chloroform, the mycotoxins ochratoxin A, citrinin, penicillic acid, sterigmatocystin, and zearalenone were easily separated by thin layer chromatography (TLC) using toluene-ethyl acetate 90% formic acid (6 + 3 + 1) developing solvent. In chemical confirmatory methods, the developed chromatogram was exposed to vapors of pyridine, acetic anhydride, or a mixture, or the mycotoxins were over-spotted. With this treatment, ochratoxin A, citrinin, penicillic acid, and zearalenone were converted to new fluorescent compounds, and observed under 365 nm light after re-chromatography with the same developing solvent. Sterigmatocystin was confirmed chemically using TLC plates impregnated with 0.6N H2SO4 or 10% oxalic acid in methanol. The described procedures are satisfactory for confirming mycotoxins present in standards, artificially contaminated grain samples (barley, corn, oat, rye, and wheat), and extracts from both fungal cultures and naturally contaminated grain samples. PMID- 6240486 TI - Brief report: replicability of factors in children's report of parent behavior (CRPBI) among orthopedically disabled and nondisabled adolescents. PMID- 6240487 TI - Observations on the mechanism of skin tumor promotion by phorbol esters. AB - Data from three different sorts of experiments that were designed to provide additional information on the mechanism of tumor formation are presented. The aim of the first approach was to obtain further evidence for the possible relevance of the induction of ornithine decarboxylase (ODC) activity to tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA) in mouse skin. The irreversible inhibitor of ODC activity, alpha-difluoromethylornithine, not only prevented ODC activity in a dose-dependent manner following skin application, it also prevented skin tumor promotion by TPA. Because in tumor promotion experiments TPA must be applied repetitively in order to elicit tumors, the effect of various time intervals between two or more applications on ODC induction and polyamine levels was investigated. Double applications at intervals greater than 48 hr led to a larger induction of ODC than after a single application. In contrast, at intervals of 24 hr or less, the first application caused a refractory state; the second application did not induce ODC activity even at times after ODC activity had returned to the very low, control activity. The aim of the third approach was to more directly determine the function of TPA in the promotion process by identifying the receptor(s) for TPA and to ascertain the function of the receptor(s). A receptor was purified from the particulate protein fraction of mouse brain and it was found that divalent calcium and phosphatidylserine were essential for the maintenance of binding activity during purification. Furthermore the receptor copurified with protein kinase C; it may be that a TPA receptor is protein kinase C and that TPA activates phosphorylating activity. PMID- 6240488 TI - Membrane interaction and modulation of gene expression by tumor promoters. AB - Phorbol ester tumor promoters bind to specific cellular receptors (probably protein kinase C) and modulate membrane structure and function and gene expression of target cells. Using cell culture systems, we are studying the interaction of phorbol esters with the cellular membrane and subsequent modulation of gene expression. Our recent results can be summarized as follows: 1) specific binding of phorbol esters to mammalian cells can be inhibited by a human placental factor, which we have partially purified and characterized. 2) Phorbol ester tumor promoters reversibly inhibit intercellular communication, as measured by electrical coupling and dye transfer between cultured cells, suggesting that they inhibit both ionic and molecular transfer between cells. 3) In vitro transformation of Balb/c 3T3 cells results in blockage of intercellular communication between normal and transformed cells, indicating that blocked intercellular communication may play a role in cell transformation. 4) 12-O Tetradecanoylphorbol-13-acetate (TPA) can continuously inhibit differentiation and globin gene expression in Friend erythroleukemia cells, without affecting their growth rate, for about 3 years. Both globin gene expression and terminal differentiation of Friend cells occur again upon removal of TPA from culture medium during such long-term culture. PMID- 6240489 TI - Phorbol ester receptors-insights into the initial events in the mechanism of action of the phorbol esters. AB - Specific phorbol ester receptors are found in the particulate fraction of cells. In addition, cytosol contains a phorbol ester apo-receptor, which requires phospholipids for reconstitution. The apo-receptor corresponds to protein kinase C, and the quantitatively major membrane receptor appears to be a protein kinase C-phospholipid complex. The ability to reconstitute the phorbol ester apo receptor into different lipid domains permits analysis of the role of the lipid domain in phorbol ester receptor function. Studies reviewed here indicate that diacylglycerols competitively inhibit phorbol ester binding, consistent with their being the postulated endogenous phorbol ester analogs. Highly lipophilic phorbol esters only inhibit effectively if incorporated into the lipid phase, indicating that the membrane dissolved form of the ligand can be recognized. The binding affinity of [3H]phorbol 12,13-dibutyrate for holo-receptor depends markedly (greater than 20-fold range) on the phospholipid environment, and heterogeneous phorbol ester binding (i.e., curved Scatchard plots) can be generated by use of heterogeneous lipid environments in the reconstitution. The possible existence of other phorbol ester receptors in addition to protein kinase C-phospholipid complexes remains to be resolved. PMID- 6240490 TI - Structure of the cell wall proteogalactomannan from Neurospora crassa. I. Purification of the proteoheteroglycan and characterization of alkali-labile oligosaccharides. AB - Proteoheteroglycan (PHG) was prepared from Neurospora crassa cells by extraction with hot water followed by cetyltrimethylammoniumbromide fractionation. The polymer was purified by DEAE-cellulose chromatography followed by gel filtrations. The PHG was fractionated into five subfractions containing carbohydrate (65-88%), protein (19-36%), and a trace amount of phosphate (0.3 1.9%). The sugar compositions of the fractions were similar to each other (D mannose, 47-60%, D-galactose, 35-50%, D-glucose, 2-5%) while the fractions showed significant heterogeneity in molecular size. Mild alkali treatment of the PHG in the presence of sodium borohydride yielded three kinds of reduced oligosaccharides. Structural studies using a methylation-GC-MS method, and proton and carbon NMR indicated that the tetrasaccharide fragment is beta-D-Galf(1-5) beta-D-Galf(1-2)-alpha-D-Manp(1-2)man nitol, the trisaccharide is beta-D-Galf(1 2)-alpha-D-Manp(1-2)mannitol, and the disaccharide is alpha-D-Manp(1-2)mannitol. PMID- 6240491 TI - Structure of the cell wall proteogalactomannan from Neurospora crassa. II. Structural analysis of the polysaccharide part. AB - The native proteoheteroglycan (PHG) from mycelia of Neurospora crassa contain two kinds of carbohydrate chains differing structure. The oligosaccharides containing mannose and galactofuranose are attached by O-glycosidic linkages to serine or threonine residues in the protein (J. Biochem. 96, 1005-1011, 1984). The second kind of carbohydrate chain is a polysaccharide containing mannose and galactofuranose as the main sugar components. The results of structural studies with methylation and NMR analyses on the native PHG and some of its specifically degraded products obtained on partial acid hydrolysis and acetolysis indicate that the polysaccharide moiety of the PHG has an (alpha 1-6) linked mannan backbone with mainly (alpha 1-2) linked side chains, each of which consists of 2 to 5 mannose units, and most of the mannosyl side chains bear beta galactofuranosyl residues linked to the 2 positions of the mannosyl nonreducing terminals. The galactofuranose residues are linked with each other by (beta 1-5) bonds. PMID- 6240492 TI - Calcium releasing action of quercetin on sarcoplasmic reticulum from frog skeletal muscle. AB - The release of Ca by quercetin from the sarcoplasmic reticulum has been claimed to be a result of the well-known inhibition of Ca2+-ATPase activity, or to be due to an intrinsic property of quercetin. To get a clearer understanding of the effect of quercetin, we examined it using fragmented sarcoplasmic reticulum (FSR) from bullfrog skeletal muscle. The rapid phase of Ca release (hereafter simply referred to as "Ca release") from loaded FSR was almost completed within 5 s after addition of quercetin in the presence of ATP. It cannot be ascribed to the inhibition of Ca2+-ATPase activity on the basis of following findings. First, when Ca uptake was driven by carbamylphosphate, no or little Ca release was observed in marked contrast to a stronger reduction in the rate of Ca uptake. Secondly, procaine reverses the Ca releasing action of quercetin, whereas it show a synergistic action in the inhibition of Ca2+-ATPase activity. Thirdly, HFSR released more Ca than LFSR, while the Ca2+-ATPase activities of both fractions were inhibited to a similar extent. The Ca release by quercetin is enhanced by ATP or beta, gamma-methylene adenosine triphosphate, and decreased by procaine or a high concentration of Mg2+. In the presence of 2.5 mM caffeine, the amount of Ca2+ released by quercetin was decreased, and the dose-effect relationship was shifted to higher doses of quercetin. This indicates that quercetin and caffeine probably overlap in the site(s) of the action, but that quercetin is dissimilar from halothane in the mode of its Ca-releasing action. PMID- 6240493 TI - [Induction of suppressor cells by antigen-pulsed macrophage-like cell line (J 774, P 388 D1)]. PMID- 6240494 TI - Ophthalmoplegic migraine with proximal posterior cerebral artery vascular anomaly. AB - We report herein the unique finding of a small perimesencephalic vascular anomaly in a patient with a partial oculomotor nerve palsy and a 25-year history of recurrent ophthalmoplegic migraine. PMID- 6240495 TI - Ophthalmoplegic migraine. AB - A 5-year-old girl developed severe periocular pain lasting 4 days. As the pain subsided, a right oculomotor palsy developed which slowly resolved without aberrant regeneration over a 2 1/2-month period. A classic history and normal high-resolution CT scan were essential in making the diagnosis of ophthalmoplegic migraine. This is a rare disorder classically requiring normal cerebral angiography for diagnosis. With the advent of high-resolution CT scanning, angiography may no longer be indicated in the typical case. PMID- 6240496 TI - Cecocentral scotomas in gliomatosis cerebri. AB - A previously healthy 69-year-old white male presented with slowly progressive, painless loss of vision in both eyes. Bilateral cecocentral scotomas were found, and this was his only chief complaint for 9 months. Signs of progressive neurologic dysfunction ensued, and the patient was followed through a complete neuropathologic study at postmortem examination. To our knowledge, this is the only reported instance of pathologically confirmed gliomatosis cerebri with an initial presentation of bilateral chronic cecocentral scotomas. PMID- 6240497 TI - Paraneoplastic retinopathy. AB - Paraneoplastic retinopathy appears to represent a nonmetastatic remote effect of carcinoma and is characterized by rapid visual deterioration accompanied by narrow arterioles seen on ophthalmoscopic examination and an extinguished electroretinogram. This syndrome has been described in postmenopausal women, and it is possible that it represents an autoimmune disorder. Corticosteroid therapy may arrest the visual deterioration. PMID- 6240498 TI - Papilledema and dural sinus obstruction. AB - We present two cases of meningioma obstructing the posterior sagittal sinus, producing elevated intracranial pressure and papilledema by impairing cerebral venous drainage. In both patients, this mechanism was not recognized preoperatively and resulted in optic atrophy and significant visual loss. PMID- 6240499 TI - Cerebral infarction and subdural hematoma. Advantage of nuclear magnetic resonance imaging in cerebral ischemia. AB - Visual hallucinations were the initial complaints in a patient with a posterior cerebral artery occlusions who fell and sustained bilateral subdural hematomas. In addition to poor vision, the patient experienced formed visual hallucinations of the epileptic type in the hemianopic field. The hemianopia was dense with macular sparing. CAT scans, which were done pre- and postoperatively, showed no abnormalities in the temporal and occipital lobes to explain the "epileptic visual hallucinations" and macular sparing. The NMR scan showed low-density changes in those areas. At the time that the NMR scan was done, most of the patient's deficits, including the hemianopia and hallucinations, had resolved. PMID- 6240500 TI - Ischemic optic neuropathy following secondary intraocular lens implantation. AB - Ischemic optic neuropathy occurred 10 days after secondary implantation of an intraocular lens in an otherwise healthy 50-year-old man who had undergone two other previously successful cataract operations. General anesthesia was used and postoperative intraocular pressures were normal. Postcataract extraction ischemic optic neuropathy is compared and contrasted to nonarteritic ischemic optic neuropathy occurring in phakic patients. PMID- 6240501 TI - Neurilemmoma of the frontal-ethmoid sinus simulating a mucocele. A case report. AB - A 48-year-old black female had a 1-year history of increasing proptosis and headache. Sinus films and CT scan demonstrated an expansive soft tissue mass in the right frontal-ethmoid sinus with lateral displacement of the medial orbital wall, consistent with a mucocele. Resection revealed a solid tumor which was identified pathologically as a neurilemmoma. To our knowledge, this is the first published report of a frontal-ethmoid neurilemmoma presenting solely with proptosis, and also mimicking a mucocele. PMID- 6240502 TI - Optic neuritis or ophthalmic artery aneurysm? Case presentation with histopathologic documentation utilizing a new staining method. AB - An elderly woman was admitted to the hospital with a presumptive diagnosis of optic neuritis following abrupt loss of vision in her left eye. Noninvasive studies were unrevealing, and she was put on a course of prednisone. Further visual loss 2 weeks later prompted a second course of prednisone therapy. Six years later the patient died from cardiac arrest. The autopsy revealed an aneurysm arising from the origin of the left ophthalmic artery. Selected brain specimens were histologically examined by application of a newly developed staining technique capable of identifying degenerated axons in human brain tissue even after long survival periods. We traced degeneration from the site of compression at the left optic nerve to five primary visual nuclei. Furthermore, transsynaptic cellular changes were observed in the lateral geniculate nucleus. PMID- 6240503 TI - Neuro-ophthalmology in the recent European literature. Part III. Heredodegenerations, stroke, pain, and diagnostic techniques. PMID- 6240504 TI - Domiciliary dental care for handicapped elderly people. PMID- 6240505 TI - [Specific aldosterone reception by the cytoplasm of the kidney tubule cells in rats with neurogenic dystrophy]. PMID- 6240506 TI - Preparative purification of the subunits of chloroplast and Rhodospirillum rubrum coupling factors by flat-bed electrofocusing in granulated gels. AB - A rapid method for the preparative purification of the subunits of oligomeric proteins like chloroplast and Rhodospirillum rubrum coupling factors is presented. It involves the dissociation of the protein in urea and the separation of its subunits by isoelectric focusing in flat-beds of Sepharose CL-4B or Sephadex G-75 superfine, in the presence of urea and in an overnight run. Using this procedure in the pH range 5-7, we have purified to homogeneity the alpha, beta and delta subunits of chloroplast coupling factor, as well as the alpha and beta subunits of Rhodospirillum rubrum coupling factor. The full separation of the gamma and epsilon subunits of chloroplast coupling factor, which focused at the same pH, was achieved by gel filtration high-performance liquid chromatography. PMID- 6240507 TI - Use of a cloned bacteriophage gene to disrupt bacteria. AB - A plasmid, pUH51, was constructed, which contains the lysis gene E of bacteriophage phi X174, subjected to the regulatory region of the lac operon, as well as the lac repressor gene. This plasmid can readily replicate in any strain of E. coli and mediates lysis of the bacteria after induction of the cloned phi X174 gene E. Taking advantage of these properties, plasmid pUH51 was used as a tool for gentle disruption of E. coli. At cell concentrations below 5 X 10(10)/ml, the efficiency of this method, as measured by release of beta galactosidase from the cells, exceeded the efficiency of conventional methods for cell breakage. PMID- 6240508 TI - Clinical significance of left ventricular hypertrophy in dilated cardiomyopathy: an echocardiographic follow-up of 50 patients. AB - To evaluate the significance of left ventricular (LV) hypertrophy in patients with dilated cardiomyopathy (DCM), 50 patients seen between 1976 and 1983 were studied echocardiographically. We categorized the patients as four groups according to the degree of LV dilatation or hypertrophy. Group consisted of 17 patients with mild to moderate LV dilatation without hypertrophy (LV end-systolic I dimension: Ds less than 60 mm, LV wall thickness at end-systole: WTs less than 15 mm). Group II, 12 with mild to moderate LV dilatation and hypertrophy (Ds less than 60 mm, WTs greater than or equal to 15 mm). Group III, eight with marked LV dilatation and hypertrophy (Ds greater than or equal to 60 mm, WTs greater than or equal to 15 mm), and Group IV, 13 with marked LV dilatation without hypertrophy (Ds greater than or equal to 60 mm, WTs less than 15 mm). Twenty patients had LV hypertrophy and 30 patients were without LV hypertrophy at the start of this study. New York Heart Association functional classes, cardiothoracic ratio and ECG findings at the first study did not show any statistically significant differences among the four groups. During the prospective follow-up of 2.7 years in average, eight patients died of congestive heart failure including five of Group IV, and three of Group I who had progressive LV dilatation. Three patients of Group I, II and III died suddenly. Ambulatory ECGs showed life-threatening ventricular arrhythmias in all 32 patients studied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 6240509 TI - [Non-invasive estimation of transmitral pressure gradient and mitral valve area in mitral stenosis by an ultrasonic pulsed Doppler technique]. AB - We attempted to estimate transmitral pressure gradient and mitral valve area (MVA) noninvasively in mitral stenosis (MS) by a bi-directional pulsed Doppler flowmeter combined with an electronic two-dimensional echocardiograph. Eleven patients with MS in sinus rhythm were studied by cardiac catheterization. Fifteen healthy subjects (H) served as normal control. The pulsed Doppler flowmeter operated with a carrier frequency of 2.5 MHz, a pulse repetition rate of either 5 KHz or 10 KHz and a sample volume of 1 X 3 X 3 mm. The velocity of transmitral central flow was measured by this system, monitoring audible Doppler sounds and cardiac images which depict the anatomic location of the sampling site. The Doppler signal was analyzed by a sound spectrograph. In estimating the transmitral pressure gradient and MVA, we employed a Doppler parameter (half time) defined as the time for instantaneous maximal blood flow velocity to reduce to one-half from its rapid inflow peak, which is independent of the angle between the ultrasonic beam and blood flow. Transmitral pressure gradient (delta P100) was measured as the pressure gradient between either left atrial or pulmonary capillary pressure and left ventricular pressure at the point after 100 msec from the nadir of left ventricular early diastolic pressure [( LA or PC--LVDP]100). MVA was obtained using a Gorlin's formula. The transmitral blood flow velocity in both MS and healthy groups revealed a narrow frequency band pattern with two peaks, R and A, in diastole. The former peak occurred during rapid inflow phase and the latter following atrial contraction. In the healthy group, the descent rate of R wave was increased than that in the MS group. The square root of the pressure gradient also reduced linearly with transmitral flow velocity in the MS group. Thus in the MS group, the transmitral velocity was directly proportional to the square root of the pressure gradient as described by a Bernoulli theorem, and the half time was proportional to the transmitral velocity. The square of the half time (delta t2) was highly correlated with delta P100 (r = 0.97), and the inverse of the half time (delta t-1) was correlated with MVA (r = 0.76). There was no significant correlation between delta P100 and diastolic descent rate of anterior mitral leaflet (DDR). The present study indicates that the half time is useful in estimating transmitral pressure gradient and MVA in mitral stenosis. PMID- 6240510 TI - [Pathophysiology of asymmetric septal hypertrophy with special reference to the response to isoproterenol administration]. AB - To investigate the pathophysiological significance of asymmetric septal hypertrophy (ASH), echocardiograms were recorded in 25 patients with hypertension (HT) (12 with ASH, 13 with symmetric hypertrophy (SH), 19 patients with hypertrophic non-obstructive cardiomyopathy (HNCM) (eight with ASH, 11 with SH), and 12 patients with hypertrophic obstructive cardiomyopathy (10 with ASH and two with SH). In eight patients with ASH, 12 patients with SH and eight normal controls, echocardiograms were also recorded during intravenous infusion of 0.02 mu/kg/min of isoproterenol. There were no significant differences in end diastolic dimension (EDD), end-systolic dimension (ESD), percent fractional shortening (%FS), interventricular septal excursion (IVSE) and posterior wall excursion (PWE) between patients with ASH and patients with SH. Among patients with ASH, interventricular septal thickness (IVST) and its ratio to posterior wall thickness (IVST/PWT) were significantly larger in HOCM than in others. Before isoproterenol infusion, there was no significant difference in the normalized peak rate of change of left ventricular dimension during systole (pVs) between ASH and SH, and between ASH and NC. However, 5 min after isoproterenol infusion, pVs was significantly greater in ASH (7.0 +/- 2.4/sec) than in SH (4.9 +/- 1.3/sec) and in NC (4.5 +/- 1.1/sec) (p less than 0.05 and p less than 0.05, respectively). This study suggests that ASH is related to hyperfunction of the catecholamine-beta receptor system. PMID- 6240511 TI - [Cardiodynamic effects of right bundle branch block. I. The effects of right bundle branch block on right ventricular function in the hearts with normal and hypertrophied right ventricles]. PMID- 6240512 TI - [The effects of right bundle branch block on left ventricular function in the canine hearts with normal and hypertrophied right ventricle]. PMID- 6240513 TI - [Histopathology of postoperative respiratory failure in congenital heart disease with Down's syndrome]. PMID- 6240514 TI - Medical malpractice--1985. PMID- 6240515 TI - Law students/liability/compensation. PMID- 6240516 TI - [An experimental study of periodontal wound healing in streptozotocin-induced diabetic rats]. PMID- 6240517 TI - Legal issues in the medical assessment of physical impairment by third-party physicians. PMID- 6240518 TI - Acute locked facet syndrome and its treatment by manipulation under local periarticular anesthesia--Part I: Clinical perspective and pilot study proposal. AB - The clinical features of prolapsed intervertebral disc and facet joint pain are described and the condition referred to as "acute locked facet joint syndrome" is differentiated. Treatment by manipulation, with and without epidural or general anesthesia are considered, and a clinical trial of manipulation under local periarticular anesthesia is proposed. PMID- 6240519 TI - The ABO, MN, phosphoglucomutase1 (PGM1) and 6-phosphogluconate dehydrogenase (PGD) types in Chiang Mai population. PMID- 6240520 TI - Terrestrial passage theory of the moon illusion. AB - Theories of the celestial, or moon, illusion have neglected geometric characteristics of movement along and above the surface of the earth. The illusion occurs because the characteristics of terrestrial passage are attributed to celestial passage. In terrestrial passage, the visual angle subtended by an object changes discriminably as an essentially invariant function of elevation above the horizon. In celestial passage, by contrast, change in visual angle is indiscriminable at all elevations. If a terrestrial object gains altitude, its angular subtense fails to follow the expansion projected for an orbital course: Angular diminution or constancy is equivalent to distancing. On the basis of terrestrial projections, a similar failure of celestial objects in successive elevations is also equivalent to distancing. The illusion occurs because of retinal image constancy, not--as traditionally stated--despite it. PMID- 6240521 TI - Selective attention and the organization of visual information. AB - Theories of visual attention deal with the limit on our ability to see (and later report) several things at once. These theories fall into three broad classes. Object-based theories propose a limit on the number of separate objects that can be perceived simultaneously. Discrimination-based theories propose a limit on the number of separate discriminations that can be made. Space-based theories propose a limit on the spatial area from which information can be taken up. To distinguish these views, the present experiments used small (less than 1 degree), brief, foveal displays, each consisting of two overlapping objects (a box with a line struck through it). It was found that two judgments that concern the same object can be made simultaneously without loss of accuracy, whereas two judgments that concern different objects cannot. Neither the similarity nor the difficulty of required discriminations, nor the spatial distribution of information, could account for the results. The experiments support a view in which parallel, preattentive processes serve to segment the field into separate objects, followed by a process of focal attention that deals with only one object at a time. This view is also able to account for results taken to support both discrimination based and space-based theories. PMID- 6240522 TI - Paired-associate learning and priming effects in amnesia: a neuropsychological study. AB - Despite severe deficits of recall and recognition, amnesic patients can exhibit normal priming effects. Amnesic patients have also been reported to perform well on tests of paired-associate learning that involve related word pairs (e.g., table-chair). The present study investigated the role of priming effects in paired-associate learning. Experiment 1 illustrated the distinction between the memory impairment of amnesic patients and their intact priming ability. Amnesic patients were markedly deficient in learning unrelated word pairs, despite exhibiting normal priming as measured by a word-completion test involving the same words. In Experiment 2A, amnesic patients showed good paired-associate learning for related word pairs, though control subjects still performed significantly better. In addition, the good performance by amnesic patients was short-lived, and performance fell to baseline after a 2-hr delay. Control subjects performed well above baseline at all delay conditions. Experiment 2B showed that the forgetting of related word pairs by amnesic patients followed the same time course as the decay of word priming. Experiment 3 showed that amnesic patients were as good as control subjects at learning related word pairs when incidental learning and test procedures were used (a word-association test). The advantage of control subjects over amnesic patients in Experiments 2A and 2B could therefore be attributed to the explicit learning instructions that are standard in paired-associate tests. Finally, Experiment 4 showed that amnesic patients exhibited normal priming when they were asked to "free associate" to words (e.g., child) that were semantically related to previously presented words (e.g., baby). The results indicate that both priming effects and paired-associate learning of related word pairs depend on activation, a process that is preserved in amnesia. Activation can account for the findings of good performance by amnesic patients on tests of word priming (Experiments 1 and 2B), related paired associates (Experiments 2A and 2B), and word association (Experiments 3 and 4). Activation is a transient phenomenon presumed to operate on and facilitate access to preexisting representations. Control subjects can establish new associations and can strengthen preexisting associations by engaging processes that are impaired in amnesia. As a result, when explicit learning instructions are used to test paired-associate learning of related word pairs, control subjects can learn better and can remember longer than can amnesic patients (Experiments 2A and 2B).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 6240523 TI - Individual differences in loudness processing and loudness scales. AB - Parameters of the psychophysical function for loudness (a 1000-Hz tone) were assessed for individual subjects in three experiments: (a) binaural loudness summation, (b) temporal loudness summation, and (c) judgments of loudness intervals. The loudness scales that underlay the additive binaural summation closely approximated S. S. Stevens's (1956) sone scale but were nonlinearly related to the scales that underlay the subtractive interval judgments, the latter approximating Garner's (1954) lambda scale. Interindividual differences in temporal summation were unrelated to differences in scaling performance or in binaural summation. Although the exponents of magnitude-estimation functions and the exponents underlying interval judgments varied considerably from subject to subject, exponents computed on the basis of underlying binaural summation varied less. The results suggest that interindividual variation in the exponent of magnitude-estimation functions largely reflects differences in the ways that subjects use numbers to describe loudnesses and that the sensory representations of loudness are fairly uniform, though probably not wholly uniform, among people with normal hearing. The magnitude of individual variation in at least one measure of auditory intensity processing, namely, temporal summation, seems at least as great as the magnitude of the variation in the underlying loudness scale. PMID- 6240524 TI - Regulation of prolactin and its role in gallinaceous bird reproduction. AB - There are major changes in circulating luteinizing hormone (LH), prolactin (PRL), estrogens (E), and progesterone (P) in relation to the onset of reproduction, egg laying, incubation, and care of young. LH levels increase in the prelaying period, followed some days later by increased circulating levels of E, P, and PRL. Levels of these hormones tend to stabilize during egg laying with periodic ovulatory cycle changes. Around the onset of incubation PRL levels increase, while LH, E, and P levels fall. During incubation PRL reaches very high levels, falling sharply when incubation is terminated. Stimulatory effects of hypothalamic neurotransmitters, peptides, and ovarian steroids on PRL secretion have been shown. The prelaying increase is dependent on E and P and the high levels of incubation require a functional serotonergic system. The causal relationships and roles of PRL in incubation of gallinaceous birds are, however, still unclear. PMID- 6240525 TI - One dimensional thin-layer cellulose chromatographic separation of dermatan-, heparan-, chondroitin- and keratan sulfate. PMID- 6240526 TI - Development of fiber types in human fetal muscle. An immunocytochemical study. AB - Human fetal muscles have been studied using immunocytochemical methods with antibodies directed against different myosin isoforms. We show that fiber type differences can be detected as early as 15-16 weeks of gestation. At this time it would appear that both the heavy and light chains characteristic of slow myosin are found in some myotubes. PMID- 6240527 TI - Active force and sensory response of single isolated cat muscle spindles in vitro. AB - Active tetanic tension developed by stimulation of a nerve innervating single isolated muscle spindles of the cat was measured. The maximum tetanic force varied among spindles, ranging from 2.3 to 8.5 mg. For four spindles, the maximum tetanic force was converted into the force per unit cross-sectional area of nuclear chain and nuclear bag fibers. The results are discussed in terms of structural and functional complexities of the intrafusal fibers. The length tension diagram of single isolated spindles showed maximum tetanic tension occurring at a spindle length longer than 1o, which was defined as the length beyond which passive tension starts to develop. This result, which appears to be different from the corresponding diagram for extrafusal muscle, is discussed in relation to the existing reports on the mechanical properties of intrafusal fibers. Spindle sensory response vs. tetanic tension was analyzed for single isolated spindles with two independent nerve supplies, one containing sensory and the other containing fusimotor axons. The results suggest that the static discharge rate of sensory endings may be linearly related, within the range examined, to the tetanic plateau tension of intrafusal fibers. PMID- 6240528 TI - Surgically induced immunologic alterations in the child. AB - Surgery is generally believed to be an immunodepressant. This assumption is based, in part, upon studies of compromised patients undergoing major operation. Similar studies in normal adults following elective procedures are contradictory and little information is available regarding the pediatric surgical patient. This paper presents a study of immune function in children undergoing elective operation. Fifty healthy preoperative children (mean age: 20 months) were randomly selected. Ninety-five percent underwent inguinal herniorrhaphy. Operative time averaged 45 minutes (range: 30 to 90 minutes). Anesthesia consisted of Halothane and Nitrous Oxide in all cases. Approximately 2.5 cc of heparinized blood and 0.5 cc of serum were obtained immediately prior to and 2 hours following operation. Half of the children underwent assays of neutrophil function including absolute count, random migration, chemotaxis, phagocytosis, and bacterial killing. Serum was examined for opsonization of Staphylococcus aureus using the chemiluminescence method. The remaining children underwent lymphocytic quantitation including absolute count, total T cells, total B cells, T-helper cells, T-suppressor cells, and T-helper/suppressor ratio. Absolute neutrophil count increased 2.4 times preoperative values (P less than 0.01). There were, however, no significant alterations in neutrophil functional capabilities. Similarly, there was no alteration in serum opsonic capacity. There was a significant decrease in absolute lymphocyte count (6560-4013, P less than 0.01) postoperatively, and T cells, T-helper, T-suppressor, and B cells were all significantly affected (P less than 0.01 to 0.02). There was no change in the T helper/suppressor ratio.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 6240529 TI - Immunodepression secondary to malnutrition: assay by lymphocyte subset analysis using monoclonal antibodies and the cell sorter. AB - It has been well documented that the hospitalized child frequently is malnourished, and the considerably greater morbidity and mortality of such children, in large part, is due to the associated secondary immunodepression. To assess the mechanism of such immunodepression in acute and chronically malnourished subjects, we chose an experimental murine model of malnutrition. Immune function was assayed by lymphocyte subset population and mixed lymphocyte culture (MLC) assessment, determining whether an alteration of the T helper (TH) to T suppressor-cytotoxic (TS-C) lymphocyte ratio is the mechanism that produces immunoincompetence in malnutrition. Ten-week-old A/J mice were rendered acutely or chronically malnourished by graded protein restriction using a 2.5% protein diet. These animals were studied before and after protein depletion with the fluorescent activated cell sorter (FACS) and the MLC. FACS cell populations were defined by the monoclonal antibodies to THY 1.2, LYT 1 (TH), and LYT 2 (TS-C) antigens. MLC reactivity was assessed with A/J v C 57 BL/6 mouse lymphocytes and expressed as a stimulation index (S.I.). Results are expressed in Table 1, and suggest that these malnourished animals were significantly immunodepressed as measured in the MLC reaction. However, the mechanism of this depression is not mediated by an inversion of the TH/TS-C ratio. These data contrast with those previously reported for the immunodepression of the burned or traumatized patient in which the TH/TS-C ratios are reversed; these data suggest that a different, as yet to be elucidated, mechanism exists for the immunodepression of malnutrition. PMID- 6240530 TI - Forensic aspects in pediatric dentistry. PMID- 6240531 TI - Dental care for the institutionalized retarded individual. PMID- 6240532 TI - Studies on pharmacological activation of human serum immunoglobulin G by chemical modification and active subfragments. III. Mechanism of anti-ulcerous action of alkylated light chain (Fr. I-L). AB - The effects of a new anti-ulcer agent Fr. I-L, a reduced and carboxamide methylated light chain of human immunoglobulin G, on defensive factors in gastric mucosa were studied. Fr. I-L increased the mucopolysaccharide contents (hexosamine, uronic and sialic acids) in the gastric mucosa of intact rats and inhibited the decrease of mucopolysaccharide contents in the gastric mucosa of rats with phenylbutazone-induced gastric ulcers. The activation of the biosynthesis of mucopolysaccharides by Fr. I-L was suggested by tracing the incorporation of 35SO4(2-) into the gastric mucosa. The administration of aspirin or phenylbutazone caused an increase of mucopolysaccharase activity in the gastric mucosa and the concomitant administration of Fr. I-L blocked the elevation of the enzyme activities. Fr. I-L also showed inhibitory activities on the local fibrinolysis and lipid peroxidation in the gastric mucosa. PMID- 6240533 TI - Inhibition of adenosine triphosphatase in vitro by silver nitrate and silver sulfadiazine. AB - Inhibition of adenosine triphosphatase (ATPase) by silver nitrate (AgNO3) in vitro was studied in microsomal fractions or tissue homogenates of canine brain and kidney, and human kidney. In microsomal fractions, AgNO3 was an indiscriminate inhibitor of ouabain-sensitive (Na+ + K+ ATPase) and ouabain insensitive (Mg2+ ATPase) activities with 50% inhibition obtaining at concentrations on the order of 10(-7) to 10(-6)M. The enzyme was protected by cysteine. Changing the concentrations of Na+, K+, H+, Mg2+ and ATP did not alter the fractional inhibition of Na+ + K+ ATPase by a constant concentration of AgNO3. An aqueous suspension of silver sulfadiazine had an inhibitory potency similar to AgNO3. It was concluded that silver gives a different pattern of Na+ + K+ ATPase inhibition than other metallic inhibitors of the enzyme so far examined. PMID- 6240534 TI - Mathematical basis for the measurement of absolute and fractional cardiac output with diffusible tracers by compartmental analysis methods. AB - Using compartmental analysis methods, a mathematical basis is given for the measurement of absolute and fractional cardiac output with diffusible tracers. Cardiac output is shown to be the product of the blood volume and the sum of the rate constants of tracer egress from blood, modified by a factor reflecting transcapillary diffusibility, the transfer fraction. The return of tracer to the blood and distant (intracellular) events are shown to play no role in the solution. Fractional cardiac output is the ratio of the rate constant of tracer egress from blood to an organ, divided by the sum of the egress constants from blood. Predominantly extracellular ions such as sodium or bromide are best suited for this technique, although theoretically any diffusible tracer whose compartmental model can be solved may be used. It is shown that fractional cardiac output is independent of the transfer fraction, and therefore can be measured accurately by tracers which are not freely diffusible. PMID- 6240535 TI - Determination of the partition coefficient and acid dissociation constants of iodochlorhydroxyquin by an improved partition method. AB - A simple and precise method for determining partition coefficients was developed utilizing a disposable injector. The method was used to determine the partition ratio of iodochlorhydroxyquin between n-decane and phosphate-buffered saline, pH 7.4. The partition ratio was found to be 1750 with a coefficient of variation of 3%. Moreover, it was found that iodochlorhydroxyquin did not associate in n decane at a concentration less than 1 X 10(-3) M. The acid dissociation constants and the partition coefficient of the undissociated species were determined. These values corresponded well with the values obtained from spectrophotometric methods. PMID- 6240536 TI - The after-effects of stretch and fusimotor stimulation on the responses of primary endings of cat muscle spindles. AB - These experiments explore the after-effects of repetitive movements and dynamic fusimotor stimulation on the responses of primary endings of soleus muscle spindles in the anaesthetized cat. If immediately following a series of conditioning stretch and shortening movements, the muscle was held at the stretched length for 3 s before being returned to its rest length, the subsequent response to a brief dynamic fusimotor tetanus given during a slow test stretch produced only a small increase in spindle firing. If, on the other hand, the muscle was returned to its rest length immediately after the movements, the fusimotor tetanus evoked a much larger afferent burst. This difference in the size of the burst could only be observed if the fusimotor tetanus was given soon after onset of the test stretch. If it was delayed and given at a time when the test stretch passed through the length at which the muscle had been held stretched after the movements, there was no difference in the size of the afferent burst. If following the movements the muscle was held stretched for less than 3 s, the response to the subsequent tetanus was not fully depressed. Once the depressed condition had been achieved, the muscle had to be left undisturbed for up to half an hour before the response had recovered its original fully undepressed size. Conditioning repetitive stimulation of the fusimotor fibre was just as effective as using alternating movements in producing the effects. If the test tetanus, which was normally ten shocks in 50 ms, was made longer, the change in size of the impulse burst became a change in latency of onset of the response to the tetanus. Holding the muscle stretched at the end of the conditioning movements/tetanus produced a delay in onset of the response to the test tetanus without significantly altering its size. These observations have been interpreted as arising from development of stable cross-bridges between actin and myosin filaments in the intrafusal fibres. During repetitive movements or fusimotor stimulation, stable bridges become detached and during the subsequent 3 s they re attach, at the length at which the muscle is being held after conditioning.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 6240537 TI - Gold vs D-penicillamine double blind study and followup. AB - We undertook a controlled random double-blind comparing gold and penicillamine. Of the 50 patients with rheumatoid arthritis entered into the study, 34 completed the protocol. We found no significant differences in the clinical results, laboratory variables, or toxicity. Longterm followup of 55 months revealed that a significant number of patients were no longer on either drug. The notable exceptions were those who were felt to be in remission from either drug, and remained on gold, or penicillamine. No toxicity from penicillamine involving known immunological aberration has thus far been encountered. PMID- 6240538 TI - Provision of dental care for elderly handicapped people. A community dental officer's view. PMID- 6240539 TI - Depressed effector activity of OKT4+ and OKT8+ T cell subsets in lectin-dependent cell-mediated cytotoxicity to HEP-2 cells in patients with systemic lupus erythematosus. AB - The role of OKT4+ and OKT8+ T cell subsets was studied in depressed lectin dependent cell-mediated cytotoxicity (LDCC) against adherent HEp-2 target cells by peripheral blood mononuclear cells (PBMC) from patients with active systemic lupus erythematosus (SLE). LDCC activity was evaluated by detachment from the monolayer of 3H-TdR-prelabelled HEp-2 cells in a 24 hr assay at 50:1 effector target cell ratio in the presence of 25 micrograms/ml concanavalin A (Con A). Decreased levels of LDCC were performed by all studied effector cell populations of SLE patients, including both OKT4+ and OKT8+ T cell fractions. LDCC by isolated OKT8+ T cells was superior to that by OKT4+ and unfractionated T lymphocytes from all healthy and SLE subjects. This suggests that the defect of LDCC activity in SLE did not affect the inherently higher LDCC effector activity of OKT8+ to OKT4+ cells. In parallel studies a reduced proliferation of PBMC in response to Con A and failure of OKT8+ T cells to suppress Con A-induced blastogenesis was observed in patients with SLE. PMID- 6240540 TI - Guidelines to dental management of the patient under dialysis. PMID- 6240541 TI - Growth and metamorphosis of the rectus abdominis muscle in Rana pipiens. AB - Cross sections through the middle segment of the anuran rectus abdominis muscle were analyzed morphometrically at nine stages of development, from early larval life through full maturity. The numbers, sizes, and relative distributions of twitch and slow muscle fibers, newly differentiated fibers, degenerating fibers, and satellite cells were determined at each stage. The data indicate that the muscle increases slowly in size and fiber content during early larval life. New fibers appear to form primarily along the medial margin of the muscle. During mid larval stages, when thyroid hormone levels are rising, new fibers form throughout the medial portion of the muscle. At a slightly later stage, fibers in the lateral region of the muscle begin to degenerate. Structurally normal presynaptic elements are present on both degenerating fibers and the empty basal laminae of fibers that had been removed by phagocytes. Both fiber formation and fiber loss slow during midmetamorphic climax, at the time when thyroid hormone levels reach a peak in anurans and begin to decline. Degenerating fibers appear within the body of the muscle at the end of metamorphosis. By the end of the second postmetamorphic month, neither degenerating nor newly differentiated fibers are present. The muscle continues to grow through adult life primarily by fiber hypertrophy. PMID- 6240542 TI - Unchanged myosin kinase activity in hypertrophied rat heart. AB - The decrease in myosin ATPase activity observed in cardiac hypertrophy induced by cardiac overload has been related to an isoenzymic redistribution of myosin. To test the hypothesis of an additional regulation of myosin ATPase through light chain phosphorylation, we measured the myosin kinase activity together in sham operated and 50% to 100% hypertrophied rat hearts. The myosin kinase were purified approximately 600 fold with 6% yield by ion exchange chromatography and calmodulin-affinity chromatography. The presence of very important levels of proteolytic activity in the rat heart resulted in a partial loss of the myosin kinase calmodulin-dependency. The major component from both myosin kinase purified fractions was a 63 kdaltons protein. The protein content was identical in myosin kinase purified fractions from sham-operated and hypertrophied hearts. The calmodulin-dependent activity of myosin kinase, assayed in the presence of 0.1 mM Ca2+ and 10(-6) M calmodulin (about 6.6 nmol P X min-1 X mg-1), was identical in sham-operated and 50% to 100% hypertrophied hearts. Thus, myosin kinase specific activity, in these conditions, was unchanged in rat heart chronic hypertrophy. This result suggests that no direct functional relationship exists between the enzymatic properties of myosin and myosin kinase during the chronic phase of cardiac hypertrophy. PMID- 6240543 TI - Cardiac norepinephrine and intrinsic properties of isolated hypertrophied hearts from DOCA hypertensive rats. AB - Alterations in cardiac norepinephrine (NE) levels often accompany cardiac hypertrophy. The present study addresses the question of whether such differences in endogenous NE might be responsible for hypertrophy-dependent differences in acutely measured mechanical and metabolic properties of isolated rat heart preparations. Hypertrophied hearts (H) of deoxycorticosterone acetate hypertensive rats and normal hearts (N) of sham-treated rats were perfused in Langendorff fashion with atrial tissue removed. Assessment of ventricular NE after 3 to 5 min indicated that the concentration was lower in H than N but total content of the left ventricle was not significantly different. Assessment of ventricular NE after three hours suggested that some washout or depletion of NE occurred in H but not N. Mechanical and metabolic characteristics of the isovolumic preparation were determined. When compared to N, H had greater spontaneous ventricular beating rates and, when paced with field stimuli, higher systolic pressures, longer relaxation times and mechanical refractory periods, and greater oxygen consumption. When the latter was normalized for ventricular mass and systolic pressure, H utilized less oxygen/g/100 mmHg pressure than N. Elimination of the acute effects of endogenous NE by either blockade (propranolol) or depletion (reserpine) eliminated the difference in ventricular automaticity between H and N, but did not influence the other differences (or similarities) between H and N. We conclude that aside from changes in ventricular automaticity, hypertrophy-dependent alterations in cardiac mechanical and metabolic properties are not likely to be a result of differing acute influences of endogenous norepinephrine. PMID- 6240544 TI - Dracunculiasis in Igbon, Oyo State, Nigeria. AB - Studies conducted between 1978 and 1979 to determine the prevalence and site of guinea-worm transmission in Igbon, Nigeria, showed that in less than 5 years of the introduction of dracunculiasis into this community, the infection rate had reached over 75% among the economically active group. Multiple infections were rampant and the frequency of occurrence of severe incapacitation was correspondingly high as reflected by prolonged and excessive absenteeism from schools, inability to engage in farming, trading and domestic work. The peak of transmission occurred in November which coincided with the retreat of rain and the abundance of Thermocyclops nigerianus in the two adjacent ponds where active transmission occurred. While ignorance was primarily responsible for annual transmission, secondary infection resulting from unsanitary methods of local treatment, seemed to be the major cause of prolonged and severe incapacitation. PMID- 6240546 TI - Phase II study of oral administration of 5'-deoxy-5-fluorouridine (5'-DFUR) for solid tumors. AB - A phase II trial of 5'-deoxy-5-fluorouridine (5'-DFUR), a new fluorinated pyrimidine analog which has been demonstrated to have potential superiority over 5-FU and tegafur for chemotherapy of murine tumors, was performed in patients with advanced non-small cell carcinoma of the lung and metastatic pulmonary tumors. 5'-DFUR at a dose of 800 mg/m2 was given per os every day for more than four weeks. None of 15 evaluable patients with non-small cell carcinoma of the lung and 15 evaluable patients with metastatic pulmonary tumors showed a complete or partial response. Toxic effects of 5'-DFUR included anorexia (29%), diarrhea (26%), nausea (23%), vomiting (10%), leukocytopenia (10%), general fatigue (10%), liver disorder (6%) and thrombocytopenia (6%). PMID- 6240545 TI - Altered immunologic function and nitrogen metabolism associated with depression of plasma growth hormone. AB - The specific role of endogenous growth hormone in regulating nitrogen metabolism during surgical stress and infection remains unclear. We have studied splanchnic amino acid uptake and plasma concentrations in patient groups exhibiting growth hormone hypersecretion or relative growth hormone depression in response to stress. Splanchnic amino acid uptake was similar in both groups although plasma levels were significantly higher in the presence of depressed growth hormone production suggesting increased net peripheral proteolysis. In association with this latter observation. T lymphocyte subset analysis revealed a greater incidence of depressed helper to suppressor cell ratios in the presence of depressed growth hormone suggesting a greater impairment of cellular immunity. PMID- 6240547 TI - [Problems on diagnosis, treatment and prevention of hepatitis type B]. PMID- 6240548 TI - [HBV-related antigens and genetic engineering]. PMID- 6240549 TI - [Fundamental studies on the measurement of skin blood flow by a periflux laser doppler flowmeter and its clinical application]. PMID- 6240550 TI - [Studies on a serum immunosuppressive factor in multiple myeloma]. PMID- 6240551 TI - [T cell function in psoriasis. Analysis of T cell helper function in psoriasis]. PMID- 6240553 TI - [Effects of feeding on portal blood flow in patients with chronic liver diseases. Quantitative measurements using an ultrasonic duplex system composed of an electronic B-mode scanner and pulsed Doppler flowmeter]. PMID- 6240552 TI - Combination therapy of murine tumors with a degraded D-manno-D-glucan (DMG) from Microellobosporia grisea, and cyclophosphamide. AB - DMG, a degraded D-manno-D-glucan with a host-mediated antitumor activity did not significantly enhance nor inhibit the development of suppressor cells for either the antibody-forming response or the delayed hypersensitivity reaction to sheep red blood cells. Cyclophosphamide (CY), which inhibited the generation of suppressor cells, was combined with DMG in treatment of murine syngeneic tumors to obtain a higher antitumor activity. The antitumor activity of the combination against MH134 hepatoma was synergistically higher than that of either component alone. A marked antitumor effect of the combination treatment against MM46 mammary carcinoma was also shown. High levels of antitumor delayed hypersensitivity reactions were observed with this combination therapy. The possible roles of DMG and CY in this combination therapy are discussed. PMID- 6240554 TI - [Studies of reciprocal relation between NK cell activities and interferons in asbestosis]. PMID- 6240556 TI - [Development of high-frequency ultrasonic Doppler flowmeters]. PMID- 6240555 TI - [Review of the environmental control system for the severely handicapped]. PMID- 6240557 TI - [Postoperative erythroderma after cardiac operation--with special reference to pathological findings]. PMID- 6240558 TI - [Transluminal balloon dilatation of the coronary arteries]. PMID- 6240559 TI - [Results of using percutaneous transluminal coronary angioplasty in patients with stable and unstable angina pectoris and acute myocardial infarct]. AB - Transcutaneous transluminal coronary angioplastics (TTCA) was performed in 28 coronary heart disease patients (8 patients had stable and 5 others labile angina, 15 presented acute myocardial infarction, AMI). The patients with AMI received intracoronary thrombolytic treatment prior to TTCA. Successful dilatation was performed in one patient with narrowing of the main trunk of the left coronary artery, in 14 of 21 patients with the stenosis of the anterior interventricular branch and in 5 of 6 patients with the narrowing of the right coronary artery. In three cases TTCA was carried out in the presence of the occluded coronary artery, with two patients benefiting from the operation. In 5 patients with AMI in whom an attempt to dilate the lumen of the coronary artery was unsuccessful, emergency surgery for aorto-coronary shunting was conducted. This operation was also performed in the planned order in 2 angina patients. In 7 patients the failure of TTCA was explained by the impossibility to pass the dilatary sound through the stenosis of the coronary artery and in 1 case by the failure to enter the ostium of the left coronary artery with the guiding catheter. PMID- 6240560 TI - [Mortality rate among men aged 40-59 based on the data of intravital screening]. AB - The article compares the results of the screening of 3820 males aged 40 to 59 years, representative of the open population, and the mortality rate over a 6 year-follow-up. Mortality was the highest in males in whom angina pectoris was combined with "ischemic" codes on the ECG and the lowest in subjects without CHD symptoms and without codes of left ventricular hypertrophy. The study showed a fairly high prognostic value of the epidemiologic method of CHD diagnosis. PMID- 6240561 TI - [Urgent problems in the effective prevention of cardiovascular diseases]. PMID- 6240562 TI - [Dilatation (congestive) cardiomyopathy: clinical aspects, diagnosis and treatment]. AB - Clinical and electrocardiographic manifestations of congestive cardiomyopathy are considered on the basis of observations of 25 patients with this pathology of the myocardium. No clinico-electrocardiographic signs specific for this disease were found. Most characteristic were cardiomegaly, congestive cardiac failure and various disturbances of rhythm and conductivity. Thromboembolic complications in the lung and kidney vessels are frequently found. Cardiac glycosides, saluretics and vasodilators were employed in the treatment of patients with congestive cardiomyopathy but the prognosis was usually poor. PMID- 6240563 TI - [Use of percutaneous transluminal coronary angioplasty in treating acute myocardial infarct patients]. AB - Transcutaneous transluminal coronary angioplastics was performed in 8 patients with acute myocardial infarction. In five patients dilatation of the coronary artery was carried out after intracoronary thrombolytic therapy and in the 3 others without the preliminary infusion of streptokinase. The method proved effective in 6 out of the 8 patients: the diameter of stenosis of the coronary artery decreased on the average from 70.4 +/- 3.9 to 23.5 +/- 12.9%, the area of stenosis reduced from 91.1 +/- 2.3 to 40.8 +/- 12.9%. Control angiography conducted in 4-5 weeks showed that in all five patients examined, the effect of the dilatation persisted. An improvement of the contractile function of the left ventricle was also observed. PMID- 6240564 TI - [Hemosorption in the treatment of patients with immune complex lesions of the lungs]. PMID- 6240565 TI - [Device for drawing together wound edges]. PMID- 6240566 TI - [Surgical treatment of postoperative ventral hernia with multiple defects of the abdominal wall]. PMID- 6240567 TI - [Diagnosis of closed abdominal injuries]. PMID- 6240568 TI - Stimulation of growth hormone secretion with human growth hormone releasing factors (GRF1-44, GRF1-40, GRF1-29) in normal subjects. AB - Peptides of different chain lengths (GRF1-44, GRF1-40, GRF1-29) were given as a 50 micrograms i.v. bolus to five normal volunteers. Blood was collected before and until 120 min after GRF injection. No serious side effects were recorded. All GRF peptides led to a clearcut and significant increase of GH levels compared to placebo controls with the maximum occurring 15-30 min after GRF injection. There was no significant difference in the maximal GH increase after the different GRF peptides. When GRF1-44 was administered to five normal subjects over 2 days in 6- and 18-h intervals, respectively, significant increase of GH levels were recorded after each injection compared to placebo controls. Again, there was no significant difference between the maximal GH rises during the different tests. These findings show that the short GRF1-29 peptide may be used for diagnosis and therapy. In addition, in contrast to continuous infusion and administration of GRF in short intervals, GRF application in 6-h intervals leads to adequate GH responses. PMID- 6240570 TI - [Role of clinical seminars in physician training]. PMID- 6240569 TI - [Experience in teaching internal diseases in a single department]. PMID- 6240571 TI - [Main stages in the development of internal medicine in Uzbekistan]. PMID- 6240573 TI - Zimelidine distribution in a sudden death. AB - The occurrence of zimelidine, a new experimental antidepressant, in a sudden death is presented. Tissues were extracted with n-butyl chloride. Quantitation was done by capillary gas chromatography with a nitrogen/phosphorus detector. Drug confirmation was obtained by gas chromatography and mass spectrometry. Blood concentrations of zimelidine and its metabolite norzimelidine were 0.71 and 2.2 mg/L respectively. Concentrations of the drug and metabolite are also given for the urine, liver, bile, and brain. PMID- 6240572 TI - The pathogenicity of Salmonella mbandaka in specific pathogen free rabbits. AB - Salmonella mbandaka was isolated from the lungs of three rabbits that developed a peracute disease and died three to eight weeks following extensive experimental manipulation. To examine the pathogenicity of this rare serotype, clinically normal, S. mbandaka-carrier rabbits were subjected to either corticosteroid immunosuppression alone or corticosteroid immunosuppression with a minor surgical procedure. Acute or peracute salmonellosis developed in one of two rabbits immunosuppressed only, and in three of four rabbits immunosuppressed and surgically manipulated. Stressful experimental procedures may precipitate episodes of clinical salmonellosis in rabbits harboring this organism. Salmonella mbandaka, should be considered a zoonotic agent in the laboratory environment. PMID- 6240574 TI - Glucocorticosteroid response modifying factors. PMID- 6240576 TI - Genetic study of high longevity index populations. AB - Five-year multidisciplinary study of longevity in the Georgian SSR made it possible to select two populations (Abkhazian and Imeretian), in which indices of longevity were much higher, than the average level for the rural population of the whole region. The distribution of polymorphic systems of red cell enzymes (adenilate kinase, esterase D, phosphoglucomutase I, acid phosphatase, 6 phosphogluconate dehydrogenase, glyoxalase I, lactate dehydrogenase, adenosine deaminase, glutamate pyruvate transaminase, phosphoglycolate phosphatase, phosphohexose isomerase) and serum proteins (haptoglobin, Gc-component and transferrin) was studied for genetic analysis of these populations. The results indicate that for all the studied loci the observed genotypic frequencies in both populations are distributed according to Hardy-Weinberg equilibrium. The genetic comparison of the studied populations with some other neighbouring populations did not reveal any genetic peculiarities and the both populations concord with the scheme of anthropological types of Hither Asia. The study of age-related changes of gene frequencies and heterozygosity showed some age-related fluctuations of genetic indices in all age groups, but the heterogeneous nature of these deviations indicate that they may be the result of random genetic processes. PMID- 6240575 TI - A role for T cell helper factors in antibody responses to "T-independent" antigens. AB - Plaque-forming cell responses were assessed in unprimed mouse spleen cells after stimulation in vitro with SRBC or "T-independent" type 2 (DNP-Ficoll or DNP liposomes) or type 1 (TNP-LPS or DNP-liposomes containing lipid A) antigens. Rigorously T cell depleted, Sephadex G-10 passed spleen cells were almost completely unresponsive to all these antigens. In every case, responsiveness could be restored by adding supernates from concanavalin A stimulated spleen cells (Con A SN). Experiments in which supernates containing interleukin 1 (IL-1) from the P388D1 cell line, interleukin 2 (IL-2), and a non-IL-2 T cell replacing factor (IL-X) were mixed showed that optimal responses to all the above antigens could only be obtained if both IL-2 and IL-X were present. IL-2 was the only factor that had any effect alone. IL-2 restored responsiveness to different degrees depending on the antigen. This ranged from about 3% (for SRBC) to about 70% (for TNP-LPS) of the optimal response. The P388D1 supernate enhanced responsiveness only if IL-2 and IL-X were present, and only with the T independent type 2 antigens. These results demonstrate that at least some examples of both type 1 and 2 "T-independent" antigens actually require nonspecific factors one of which, IL-2, is clearly T cell derived, to stimulate antibody production by B cells. PMID- 6240577 TI - [Evaluation of the efficacy of benzoyl peroxide at high concentrations. Therapeutic and microbiological study]. PMID- 6240578 TI - Learning to be contingent: retarded children's responses to their mothers' requests. PMID- 6240580 TI - Laser recannalization of atheromatous vessels using fiber optics. AB - A laser endoscope was devised using optic fibers in order to provide a means of visualization and removal of atheromatous plaques from arteries in cadavers and experimental animals. Atheromatous plaques were satisfactorily lased off in a few seconds, although contraction of lased vessels was observed. A self-focusing fiber was shown to provide laser access to and visualization of the body via a single optic fiber of feasibly less than 0.2 mm diameter. PMID- 6240581 TI - [Raising a healthy child in the 1st year of life]. PMID- 6240579 TI - [Disorders of B cell activation in splenectomized patients]. AB - Using a reverse hemolytic plaque assay as the effector system, we studied in vitro B-lymphocyte function in 12 patients after posttraumatic splenectomy as well as in 25 normal individuals. The time interval between the splenectomy and the immunological studies varied between 2 days and 7 years. Compared to normal individuals, the splenectomized patients had markedly elevated numbers of spontaneous immunoglobulin-secreting cells and severely decreased responses to the polyclonal activator pokeweed mitogen, indicating an in vivo polyclonal B cell activation. A tendency towards normalization of these abnormalities, especially the high spontaneous ISC levels, could be observed during the time interval extending up to 7 years after splenectomy. In order to characterize the mechanism responsible for the altered immune response in splenectomized patients, in vitro experiments were performed with separated lymphocytes. These revealed an impaired T-helper cell capacity as well as an intrinsic B-cell defect. Marker analysis with monoclonal antibodies revealed normal proportions with the exception of OKT 4 positive and B 1 positive cells that identify T-helper/inducer and peripheral B-cells, respectively. We conclude that immune dysfunction in peripheral blood lymphocytes of splenectomized patients involves mainly the OKT 4 positive cell population. PMID- 6240582 TI - [Organization of the work in a consulting room for healthy child rearing]. PMID- 6240584 TI - [Health education work on the district level]. PMID- 6240583 TI - [Dispensary observation of frail children in the 1st year of life]. PMID- 6240585 TI - [Oil-induced acne in workers in the automobile industry]. AB - A group of 211 workers exposed to oils and coolants at automaton machining underwent dermatological examinations and a detailed anamnesis. The oil acne was found in 68% of the workers. PMID- 6240587 TI - Isotype specificity and heterogeneity of Fc gamma-receptors on guinea pig splenic B and T lymphocytes. AB - The isotype specificity of Fc-receptors for IgG (Fc gamma-Rs) on normal guinea pig splenic B and T cells was determined by a rosette assay using sheep erythrocytes sensitized with either homologous IgG1 or IgG2 anti-sheep erythrocyte antibody [EA(IgG1) or EA(IgG2)]. Approximately 70% of the lymphocytes in the highly purified B-cell fraction could form rosettes with EA(IgG2), and 55% of the cells with EA(IgG1). Inhibition experiments with soluble complexes of IgG1 or IgG2 antibody with ovalbumin demonstrated that approximately 20% of the EA(IgG2) rosette-forming B cells bore the Fc gamma-R monospecific for IgG2, whereas 80% of the cells had two distinct Fc gamma-Rs simultaneously; one monospecific for IgG2 and the other bispecific for IgG1 and IgG2. The existence of a B cell bearing the Fc gamma-R monospecific for IgG1 was not definitively demonstrated in the B-cell fraction. In the T cell-enriched fraction, approximately 40% of the cells could form rosettes with EA(IgG2). The EA(IgG1) rosette-forming cells, however, comprised only 6% of the total cells, indicating that most of the EA (IgG2) rosette-forming T cells bear essentially the Fc gamma R monospecific for IgG2 alone. The results obtained revealed that guinea pig splenic lymphocytes bear two distinct Fc gamma-Rs, which are not equally distributed on the B- and T-cell populations and also on their respective subsets. PMID- 6240588 TI - The aetiology of SMON may involve an interaction between clioquinol and environmental metals. AB - Clioquinol can increase the penetration of metallic cations through cellular membranes by forming lipophilic metal-chelates. It is suggested that the pathogenesis of SMON may involve an accumulation of injurious metals in nervous tissues due to facilitated uptake by complex formation with clioquinol. The Japanese have been more heavily exposed to metals by environmental pollution than the inhabitants of other countries, which may explain the prevalent occurrence of SMON in Japan. PMID- 6240586 TI - RecA protein--promoted lambda repressor cleavage: complementation between RecA441 and RecA430 proteins in vitro. AB - Induction of prophage lambda occurs in recA441 mutant lysogens after a shift to 42 degrees C in the presence of adenine. If the synthesis of RecA441 protein is maintained at a low basal level by the presence of a second mutation in the recA441 gene, recA453, induction of prophage lambda is prevented. The ability to induce prophage lambda is restored by the introduction, on a transducing phage, of a second recA gene carrying the recA430 mutation; by itself, the RecA430 protein is devoid of activity against the lambda repressor (Rebollo et al. 1984). In order to explain how the RecA430 protein might complement the RecA441 protein to provide lambda repressor cleavage in a recA453-441 (recA430) diploid lysogen, we characterized the cleavage reaction catalysed by a mixture of these proteins in vitro. Our results suggest that, in the presence of dATP, the RecA441 and RecA430 proteins form mixed multimers on single-stranded DNA, in which the RecA441 protein molecules enhance the DNA binding affinity of RecA430 protein molecules, but RecA430 protein molecules support no cleavage of the lambda repressor. Although the effects of the RecA430 and single-strand binding (SSB) proteins are similar in vitro, we show that the SSB protein cannot substitute for the RecA430 protein in restoring lambda repressor cleavage in a recA453-441 lysogen. Comparison of the stimulatory effect of long single-stranded DNA with that of (dA)14 oligonucleotides on the RecA441 protein-directed cleavage of the lambda repressor in the presence of various nucleoside triphosphates (NTPs) indicates that the cooperative binding of the RecA441 protein to single-stranded DNA stabilizes the RecA protein-DNA complexes so that they remain intact long enough to support cleavage of the lambda repressor. We conclude that the low basal level of the RecA441 protein in a recA453-441 cell is sufficient to cleave the lambda repressor, under conditions where a normal basal level of RecA430 protein is also present allowing the formation of mixed multimers on single stranded DNA regions normally present in the cell. PMID- 6240589 TI - An electro-ocular switch for communication of the speechless. AB - The designed EOG switch was based on the principle of the detection of the saccadal velocity producing a pulse above a certain selected value of the saccadal derivative. The EOG transducer is preferable above an eye switch designed on the infrared limbus-pupil reflection method because of two reasons, namely in its use for vertical eye movements and because of its low costs when composed with operational amplifiers (741) or with IC's. AC-coupling between the differential amplifier and the main amplifier excludes the effects of the well known DC-drift during EOG recording on switching. An optocoupler at the output of the switch serves for the safety of the non-vocal handicapped during the communication process with the Handiwriter. Experience is obtained with the EOG switch connected with the Handiwriter system by one quadriplegic CVA patient and one quadriplegic ALS patient. A possible group of patients as candidates for using the EOG switch has been indicated in the discussion. PMID- 6240591 TI - [Root resorption. II. Pathological rhizolysis]. PMID- 6240593 TI - Analysis of the structure and function of the receptor for immunoglobulin E. PMID- 6240592 TI - [Quantitative kinetic model of ATP hydrolysis-synthesis by membrane H+-ATPase]. AB - A mathematical model of fermentative reactions of synthesis-hydrolysis of ATP by H+-ATPase, coupled to the charge transport across the membrane has been constructed. Quantitative calculations of the rate of hydrolysis--synthesis of ATP were performed. The nature of the membrane electrochemical gradient delta mu H+ is discussed. PMID- 6240595 TI - Modulation of Fc receptor mediated functions by split products of C3. PMID- 6240594 TI - Complement C3 receptors: structure and function. AB - Significant progress has been made during the past few years toward elucidating the structure and function of various C3 receptors. Better understanding of the biochemical basis of the immune adherence phenomenon has been achieved. The availability of polyclonal and monoclonal antibodies to C3 receptors allowed more accurate studies of the cellular distribution of these receptors. Finally, advances in our knowledge of the functional properties of the C3 receptors and their relationship to specific cell surface molecules was facilitated by recognition of a patient deficient in various receptor-mediated functions. All together these developments will soon make it possible to describe in detail the molecular events involved in the modulation of complement receptor coupled cell functions. PMID- 6240597 TI - Hybridoma 2.4G2: dissociation of the B-lymphocyte-triggering activity from the monoclonal anti-Fc IgG receptor antibody. AB - Previously, we have reported that monoclonal antibody specific for mouse Fc IgG receptors (Fc gamma R) [purified by affinity chromatography using goat F(ab')2 anti-rat Ig linked to Sepharose from supernatants of hybridoma 2.4G2] can induce both proliferation and antibody secretion of normal B-lymphocytes in the absence of T-lymphocytes. The current studies have shown that the B-cell-triggering activity is associated with a substance produced by 2.4G2 which can be distinguished from the 2.4G2 antibody by several criteria: (1) different preparations of 2.4G2 antibody with identical binding capacity for Fc gamma R differ markedly in their ability to trigger B-lymphocytes; (2) the B-lymphocyte triggering substance and the anti-Fc gamma R antibody can be separated using insolubilized monoclonal mouse anti-rat kappa-antibody columns; and (3) the B lymphocyte-triggering substance has a mol. wt of less than 50,000, while the 2.4G2 antibody has a mol. wt of 160,000. The B-lymphocyte-triggering moiety produced by the 2.4G2 hybridoma may be a previously undescribed lymphokine. PMID- 6240596 TI - Role of C3b receptors in the enhancement of interleukin-2-dependent T-cell proliferation. AB - The mechanism by which the complement system influences immune responses to T cell-dependent antigens has not yet been clarified. That is why we studied the effect of the third complement component (C3) on different T-cell-dependent processes using well-defined mouse T-cell lines. While C3 did not influence the interleukin-2 (IL-2) production of the ST2/K-9 helper T-cells, the IL-2-dependent proliferation of the ST1 line was shown to be dose-dependently enhanced by C3. It is proved that neither the haemolytic activity of C3 nor the C3a fragment had any role in the process. The effect of C3 on the IL-2-dependent T-cell growth is even more enhanced (up to five-fold) when using polymerised C3. When the ST1 cell line is cultured in the presence of the cross-linked ligand, T-cells formed 80% less rosettes with red blood cells coated with antibody and mouse or human C3b. It is strongly suggested that C3--particularly when aggregated--exerts its enhancing effect on the growth of IL-2-dependent cell lines by binding to C3b receptors present on such T-cells. PMID- 6240598 TI - Induction of Fc receptors and immunoglobulin-binding factors in T-cell clones. PMID- 6240599 TI - [Bronchial asthma in childhood. Therapy with fenoterol and ipratropium bromide powder]. AB - In a double blind randomized study during a period of 2 weeks we compared the therapeutic effectiveness and side effects of IK-6-Inhaletten (0.1 mg Fenoterol + 0.04 mg Ipratropiumbromide) and SCH 1000-Inhaletten (0.2 mg Ipratropiumbromide) in 39 children (4-14 years) suffering from mild, moderate or severe asthma bronchiale. All measurements were performed with a whole body plethysmograph. In contrast to SCH 1000-inhalation after inhalation of IK-6-Inhaletten, we found a good improvement of the total airway resistance Rtot, the specific airway resistance SRaw and the forced exspiratory volume FEV1. Especially SRaw was significantly diminished compared to the less effective SCH 1000-inhalation. IK-6 inhalation allowed to decrease the amount of bronchospasmolytic therapy in our group of patients. We did not observe any severe side effects after inhalation of IK-6 or SCH 1000. In summary, we recommend the application of the IK-6-Inhaletten in children suffering from mild and moderate asthma bronchiale. PMID- 6240590 TI - Interactions of bacteriophage and host macromolecules in the growth of bacteriophage lambda. PMID- 6240600 TI - On the 80th anniversary of Professor Benedict Menkes. PMID- 6240601 TI - The role of the cerebrospinal fluid during embryonic development. A biochemical study. AB - The total protein content and the protein fractions were determined in the blood serum and the cerebrospinal fluid (CSF) of chick embryos and foetuses between the 4th and 20th day of incubation and of 2-day-old chickens (by Lowry's method and by polyacrylamide gel electrophoresis respectively). The main results were the following: The total protein content of the CSF increased from 1.8 mg/ml on day 4 to 3.1 mg/ml on day 10. After a slight decrease to 2.6 mg/ml on day 12 no further changes were detected. In the blood serum the total protein content was 4.3 mg/ml on day 4 and 4.7 mg/ml on day 9. Beginning with day 10 it increased constantly to 23.2 mg/ml on day 2 after hatching (daily rate 1-1.2 mg/ml). It results that the "protein barrier" between blood and CSF begins to function after 10-12 days of incubation. Of the protein fractions determined, the light fraction I in the CSF represents 50 per cent of the similar blood serum fraction (on day 10). As to the heavy fractions XI-XIV, their concentration in the CSF represents, beginning with day 10, 51 per cent of the similar blood serum fraction (until the end of the period investigated). It results that the "protein barrier" has an active, selective character. Some comparative aspects with literature data are discussed. PMID- 6240602 TI - Increased autophagocytosis induced by colchicine in rat sympathetic neurons. AB - The effect of colchicine was followed up in the superior cervical ganglion of rats. An increase was observed in the number of autophagocytosis vacuoles in the neurons, especially three and four hours after the intraperitoneal injection of colchicine (0.05 mg/100 g.b.w.). These vacuoles presented very various ultrastructural characters due to their different content and stage of degradation. Their high number is explained by the action of colchicine upon cytoplasmic microtubules, the secondary inhibition of the intracellular movement, and the blockage or reduction of the fusion of primary lysosomes with the autophagic vacuoles, which are continuously formed in the neuron cytoplasms, as well as in other cells. PMID- 6240604 TI - Particular ultrastructural aspects in some splenectomized cases of hairy cell leukemia. AB - Some peculiar ultrastructural aspects of hairy cells obtained from the examination with SEM and TEM are presented. Images of erythrocyte rosette formation around hairy cells in spleen as well as some additional data on the biogenesis of ribosome-lamellae complexes are reported. Some considerations on the origin of hairy cells are added. PMID- 6240603 TI - The epidermoid (squamous cell) carcinomas of the lung. A histopathological analysis of 2,150 diagnosed cases. AB - A histopathological analysis of 2,150 cases of lung epidermoid (squamous cell) carcinomas, diagnosed between March 1949 and December 1983, was performed. The ratio men/women was 14.9:1. The study included 851 lung surgical specimens (199 pulmonectomies, 456 lobectomies and 196 segmentectomies, atypical resections and lung biopsies). 1,103 bronchial biopsies of inoperable cases, 91 peripheral lymph node biopsies, 19 pleuroparietal biopsies, and 86 autopsies. Immature, unkeratinized forms were found in 471 cases, a low tendency to keratinization in 830 cases, and mature, well keratinized forms in 849 cases. Necrosis of neoplastic tissue occurred in 332 cases (15.5 per cent). The most frequent metastases were found in hilar and mediastinal lymph nodes: 71 surgical specimens and autopsies. In the ensemble of histodiagnosed cases of lung carcinomas (between 1949 and 1983), the epidermoid carcinomas of the lung, which presented an incidence of about 55 per cent 15 years ago, have decreased to 36 per cent in the last five years. Differentiating criteria between immature forms of epidermoid, cylindrocubic and macrocellular carcinomas of the lung were established. The importance of epidermoid metaplasia of bronchial epithelium and of intraepithelial proliferations in the histogenesis of epidermoid carcinomas of the lung is discussed in the light of experimental data. PMID- 6240605 TI - Gastrobiopsy in the diagnosis of gastric stump carcinomas. AB - An endoscopic and histopathologic observation made on 152 cases with gastric symptoms occurring 5-35 years of free interval after gastric resection revealed a gastric stump carcinoma in 14 (9 per cent) of the cases. Research pointed out that previous duodenal ulcer prevailed as compared to the gastric one, and the stomal located carcinomas co-existed with severe dysplasia of the gastric mucosa in six cases. PMID- 6240606 TI - Influence of negative air ions on liver regeneration. AB - Partial hepatectomy led to an increased oxygen consumption over the whole respiratory cycle. Association of partial hepatectomy with negative aeroionotherapy determined a decrease of oxygen consumption as compared with the partially hepatectomized animals. Negative air ionization in controls determined a decrease of oxygen consumption at the level of the NAD+ dependent enzymes. On the other hand, neither partial hepatectomy, nor negative air ionization altered the oxidative phosphorylation of mitochondria. PMID- 6240607 TI - Improvement of complement fixation test antigen for the diagnosis of Mycoplasma hyopneumoniae infection. AB - Several attempts were made to develop a complement fixation test antigen which is useful and practicable for the diagnosis of mycoplasmal pneumonia of swine. For the preparation of antigen, Mycoplasma hyopneumoniae was grown in broth medium containing horse serum for 14 days by shaking culture. Anticomplementary activity of antigen was eliminated by addition of complement and heating at 56 degrees C for 30 minutes. Storage of this antigen at 4 degrees C or at room temperature for 12 months had no significant effect on antigen titer. In the complement fixation test with this antigen, complement-fixing antibodies could be detected up to 41 weeks after experimental inoculation by KIO4 treatment of serum. They were demonstrated in 81.4% of 296 sera collected at slaughterhouses in five prefectures. PMID- 6240608 TI - [Endemic aphthous stomatitis in mentally handicapped persons]. PMID- 6240610 TI - [New possibilities in the treatment of hepatic metastasis of colo-rectal carcinomas]. PMID- 6240609 TI - Molindone compared to haloperidol in a guinea-pig model of tardive dyskinesia. AB - Molindone was compared with haloperidol in animal models of tardive dyskinesia. Treatment with molindone for 14 days at 3, 6, 20 and 40 mg/kg, enhanced the stereotyped behavioral response induced by apomorphine and increased the numbered of D-2 dopamine receptors in the striatum (Bmax) labelled by high affinity (Kd = 40 pmol) binding or [3H] spiroperidol in the guinea-pig. Molindone at 1 mg/kg, caused no behavioral supersensitivity or change in the binding of dopamine receptors. Chronic administration of haloperidol (0.1, 0.5 and 5.0 mg/kg) also increased both the behavioral response to apomorphine and the number of dopamine receptors. Haloperidol, at 0.02 and 0.004 mg/kg, had no effect. Molindone potentiated dopaminergic activity in animal models in a similar way to other neuroleptics, suggesting that its use may also result in tardive dyskinesia. PMID- 6240611 TI - Actions of excitatory amino acids and kynurenic acid in the primate hippocampus: a preliminary study. AB - Orthodromic evoked potentials of CA1 pyramidal cells were studied in superfused slices of marmoset hippocampus. N-methylaspartate, quinolinic acid and quisqualic acid depressed the responses, but only the former two compounds appeared to be antagonized by 2-amino-5-phosphonovalerate. Kynurenic acid also reduced the orthodromic evoked responses but had no effect on antidromic potentials, the blocking action therefore probably resulting from an interference with synaptic transmission. The study reveals receptors for N-methylaspartate, quisqualate, quinolinate and kynurenic acid in the primate hippocampus broadly comparable with those previously studied in non-primate vertebrates. PMID- 6240612 TI - [Effect of epinephrine on the microvascular blood flow in the tongue of rabbits using Laser Doppler Flowmeter]. PMID- 6240613 TI - [Significance of forms of selected infectious enteritis]. PMID- 6240614 TI - [Minimal requirements of vision in lifeguards]. PMID- 6240615 TI - [Sports and exercise therapy in rehabilitation--an empirical survey of requirements for sport teachers]. PMID- 6240616 TI - [Technical health equipment of the health office--a report of experiences]. PMID- 6240617 TI - [Cooperation of the public health physician and the medical psychology examination station in the evaluation of driving ability]. PMID- 6240618 TI - [Public health problems in the disinfection of drinking water with ultraviolet equipment]. PMID- 6240619 TI - [Possibility of error in the use of disinfectants]. PMID- 6240620 TI - [Thoughts on health education]. PMID- 6240621 TI - Blue Cross and Blue Shield of Michigan's efforts to change practice patterns. PMID- 6240622 TI - [Economic effectiveness of the rehabilitative management of invalids with sequelae of crural bone fractures]. PMID- 6240623 TI - Control and persistence mechanisms of viral infections. PMID- 6240624 TI - Immune-recognition of Schistosoma mansoni primary sporocysts may require specific receptors on Biomphalaria glabrata hemocytes. AB - Cellular interactions, leading to cell-mediated cytotoxicity when Biomphalaria glabrata hemocytes encapsulate Schistosoma mansoni sporocysts, have been investigated. Rabbit antibodies (IgG), when bound to antigens on sporocyst surfaces, prevent the normal cytoadherence (CA) of hemocytes from both susceptible and resistant host snails. Since interference with CA occurs with even fixed sporocysts, the effect is not due to IgG stimulated modulation of the parasite surface. Using two antisera with some overlapping specificities, and quantitative immunofluorescent antibody technique (QIFAT), we determined the concentrations of IgG needed to place equivalent amounts of IgG on the sporocysts. At these concentrations, CA was affected differentially, implying that interference was due to the specific antigens bound, and not due simply to the presence of IgG. Also with QIFAT we determined how much F(ab')2 and IgG from anti-sporocyst serum were needed to block an equivalent amount of antigenic determinants from access by whole FITC labelled IgG. Sporocysts whose surface antigens were equally blocked were equally unadherent for hemocytes, supporting the notion that the nature of obscured antigens, and neither the Fc portion nor the larger size of intact IgG protein, was responsible for the effect on CA. These surprising results imply a role for specific antigen binding sites on snail hemocytes. PMID- 6240625 TI - Role of cellular immunity in protection against Trypanosoma cruzi in mice. AB - The importance of antibodies in the maintenance of immunity against Trypanosoma cruzi in mice is emphasized by the failure of either immunization or transfer of immune T cells to afford B cell suppressed mice complete protection against a lethal infection. Both procedures did, however, significantly prolong survival indicating a contributory role for T cells other than simply as helper cells in antibody production. The complete protection afforded intact mice following transfer of immune T cells can be attributed to a significant T cell-mediated augmentation of IgG antibody production. PMID- 6240626 TI - [Level of parasitic contact in colonies of the little suslik in the semideserts of western Kazakhstan]. AB - Field experiments were conducted during the settling of young animals of Citellus pygmaeus in four areas 4 to 13.6 hectares in size. From 3 to 6 animals were caught in each area and labeled by administering radioactive substance (0.5 micrograms of glycine 14C or methionine 35S) and colouring hair on the head. In a day or two labeled sousliks were caught again and in 6-7 days a total catching of animals and collection of ectoparasites from their hair and burrows done. In al, 942 sousliks were caught in the experimental areas and 2624 specimens of fleas of different species and 2305 ticks of R. schulzei collected. The average number of fleas which were labeled on one little souslik for a day was 0.1 to 2.3. The number of labeled fleas in the above areas coincided with the number of fleas infected with plague in the areas of epizootia. The level of parasitic contact in settlements of little souslik cannot provide the development of plague epizootia by transmission of the agent through fleas. PMID- 6240627 TI - [Biology of mosquito Aedes impiger (Culicidae) and its possible role as a phenological indicator]. AB - The biology of Aedes impiger Walk. from the polar region of the European part of the USSR has been studied and literary data have been summarized. Its biological peculiarities such as rapid and simultaneous development of larvae and pupae, a short period of seasonal activity, long daily activity, the presence of autogeny and long obligate diapause provide a distinct localization of the active period of the life cycle within a season. A. impiger develops quicker than other spring species of mosquitoes, emerges the first and can serve as phenoindicator for specification of developmental periods and mass emergence of bloodsucking mosquitoes. PMID- 6240628 TI - [History of parasitology in Leningrad]. AB - The paper reports the initial stages of the formation of ecological parasitology in the Leningrad University in thirties. A special attention is paid to the activities of A. A. Philipchenko (1884-1940) whose role has been little known up to now. PMID- 6240629 TI - [Relation between blood potassium and sodium concentrations, ATPase activity and ATP level in patients with burns]. PMID- 6240630 TI - Myocardial excitation-contraction coupling in the fetus of alloxan-diabetic rabbit. AB - This study was conducted to investigate myocardial excitation-contraction coupling in the fetus of the diabetic rabbit (FDM). On day 14 of gestation, diabetes was induced in pregnant rabbits by alloxan injection. On day 28 of gestation, mechanical function of the fetal myocardium was determined in the isolated arterially perfused heart preparation. At 1.5 mM [Ca2+]o (control), the force of myocardial contraction in FDM was not significantly different from that in the control fetus. At higher [Ca2+]o, developed tension and maximal rate of tension development [+dT/dt (max)] in FDM were significantly greater than in the control fetus. High [Ca2+]o caused significant increases in resting tension and half-relaxation time (toxic effects) in the control fetus, but not in FDM. Perfusion with lanthanum (known to displace sarcolemma-bound Ca2+ and block sarcolemmal Na-Ca exchange) decreased developed tension and +dT/dt (max) and increased resting tension and these effects in FDM were significantly less than in the control fetus. Perfusion with manganese (known to displace Ca2+ from intracellular sites) also decreased developed tension and +dT/dt (max) and increased resting tension, and these effects were similar in the two groups. The myofibrillar ATPase activities at various calcium concentrations were not different between the two groups. The rates of Ca2+ uptake by mitochondria and sarcoplasmic reticulum were similar in the two groups. These data suggest that in FDM the inotropic effect of Ca2+ is greater and the toxic effect of Ca2+ is less than in the control fetus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 6240631 TI - [60 years of child health services in Uzbekistan]. PMID- 6240632 TI - Preliminary validity study of the pain disability index. PMID- 6240633 TI - Lipid intermediates in chronically volume-overloaded rat hearts. Effect of diffuse ischemia. AB - Tissue contents of intermediates of fatty acid metabolism were determined in isolated volume-overloaded rat hearts, 3 months after creation of an aorto-caval fistula. In the absence of any modification of blood carnitine, tissue levels of total carnitine were reduced by 33% in overloaded hearts compared to normal hearts. Total tissue CoA was unchanged. Fifteen minutes of whole-heart ischemia (i.e. a 50% reduction in coronary flow) did not increase levels of long-chain acyl esters of CoA and carnitine of the overloaded myocardium, in the presence of glucose as the only exogenous substrate. This was associated with lower than normal levels of long-chain acyl carnitine under normoxic conditions. The addition of exogenous palmitate (1.5 mM) resulted in an ischemia-induced accumulation of long-chain acyl-CoA and acyl carnitine in the overloaded heart although to a smaller extent than in the normal heart under similar perfusion conditions. PMID- 6240634 TI - Biomechanical significance of the correct length of lower limb prostheses: a clinical and radiological study. AB - The length of the lower limb prosthesis was compared with the length of the contralateral lower extremity in 113 Finnish war-disabled amputees by a radiological weight bearing method developed by the author. Considering a shortening of 10 mm for above-knee prostheses and of 5 mm for below-knee prostheses as tolerance limits, the length of the prosthesis was acceptable only in 17 cases (15% of the total group). In 79 cases (70%) the prosthesis was up to 47 mm too short and in 17 cases (15%) up to 40 mm too long. Chronic pain symptoms of low back, hip and knee correlated significantly with the lateral asymmetry caused by incorrect length of the prosthesis. Independently of the side of amputation, the unilateral sciatica and chronic hip pain occurred mainly on the long leg side. Physical activity of the lower limb amputees seemed to correlate with the suitability of the length of the prosthesis, and was unrelated to the length of the amputation stump. PMID- 6240635 TI - Evolutionary coorigin of the RNA polymerase sigma factor and the lambda repressor inferred from gene nucleotide sequence homologies. AB - The lambda phage cI gene and E. coli rpoD gene encoding the lambda repressor and sigma factor, respectively, were aligned with each other based on the internal homologies found in the rpoD gene. Statistical evaluations for these intragenic and intergenic base sequence homologies in the corresponding alignments have conclusively demonstrated that the rpoD gene must have evolved by repeated gene duplications from a primitive gene closely similar to and co-ancestral to the cI gene. PMID- 6240637 TI - Children's dental treatment in general and pedodontic practices. PMID- 6240636 TI - Syntheses of 18F-labeled pyrimidines and their usefulness for tumor imaging. AB - 18F-Labeled 5-fluorouracil(FUra), 5-fluoro-2'-deoxyuridine(FdUrd) and 5 fluorouridine(FUrd) were synthesized with high radiochemical purities. Biodistribution of the 18F-pyrimidines in tumor-bearing rats, mice or a rabbit was examined. Blood clearance of the 18F-pyrimidines was very rapid. The kidney and liver showed the high uptake and rapid clearance which was due to the metabolism and excretion. The 18F-concentration in the tumor was due to the metabolism and excretion. The 18F-concentration in the tumor was also high and clearance was very slow compared with those in other organs. Tumor uptakes of 18F FdUrd were also shown by positron emission tomography and autoradiography. Biodistributions of the 18F-FdUrd and radio-deoxythymidine(dThd) were different between several organs, but similar distribution patterns in the tumor were observed by autoradiography. PMID- 6240638 TI - Impact of the ADA Special Committee on the Future of Dentistry report on pedodontic education. PMID- 6240639 TI - Implications of the American Academy of Pedodontics Future of Dentistry report for pedodontic educators. PMID- 6240641 TI - The American Board of Pedodontics examination: an evolving instrument (1949-84). PMID- 6240640 TI - Case history: a bottleneck, hang-up, or just a put-off? PMID- 6240642 TI - Early prenatal sonographic appearance of rare thoraco-abdominal eventration. AB - Fetal ventral wall malformations may be diagnosed prenatally with ultrasound. These include omphalocele, gastroschisis, or even thoracic defects with or without ectopia cordis. It is important whenever such a defect is found to carefully define the full extent of the lesion prior to parental counselling. Described and illustrated here is the prenatal diagnosis with real-time ultrasound at 17 weeks gestation of a rare thoraco-abdominal ventral wall defect including omphalocele, bifid sternum, diaphragmatic aplasia, and pericardial aplasia with incomplete ectopia cordis. The technique is described and the importance of the complete, accurate delineation of anatomic malformations is emphasized. PMID- 6240643 TI - [How to evaluate a conduction disorder?]. PMID- 6240644 TI - [Hairy cell leukemia: study of the development of 211 cases]. AB - Large series of patients with hairy cell leukaemia have only recently been published. The 211 cases reported here provide useful information on the clinical presentation, prognostic factors, evolution and management of this uncommon disease. At presentation, 28% of the patients had no spleen enlargement, and only 20% had severe pancytopenia. However, severe neutropenia (less than 0.5 X 10(9)/l) was present in 32% of the cases. Prognosis was primarily related to the degree of peripheral cytopenia, usually corrected by splenectomy, but it was poor in both non-splenomegalic and splenectomized patients with persistent anaemia and neutropenia, and it is in these patients that other treatments should be tested. PMID- 6240646 TI - [Established caustic stenosis of the esophagus in children. Closed-thorax esophagectomy with in situ colonic esophagoplasty]. AB - Replacement of the oesophagus with a colonic graft brought up to a retrosternal or intrathoracic position is usually performed in children with undilatable oesophageal stenosis resulting from caustic burns. However, incidents associated with the oesophagus remaining in situ regularly raise the problem of concomitant or delayed oesophagectomy and therefore thoracotomy. A one-stage surgical technique is described, which includes closed-thorax oesophagectomy and colonic oesophagoplasty in situ in the oesophageal bed. The 3 patients operated upon by this method made an uneventful recovery. PMID- 6240645 TI - [Determination of anti-native DNA antibodies by immunofluorescence on Crithidia luciliae. Correlation between renal involvement and the presence of high-avidity anti-native DNA antibodies in lupic disease]. AB - Low avidity native DNA - anti-native DNA complexes dissociate at alkaline pH and in high molarity solutions. This property was used to modify the indirect immunofluorescence reaction on Crithidia luciliae in order to assay high avidity anti-native DNA antibodies resistant to alkaline and strongly saline solutions. Assays were performed in the sera of 36 patients (31 women and 5 men) with systemic lupus erythematosus (SLE). Seventeen of these patients had histologically significant lupus nephritis (WHO types III, IV and V) and 19 had no renal, urinary or biochemical abnormalities. The mean titer of total anti native DNA antibodies was similar in both groups, but the titer of high avidity anti-native DNA antibodies was significantly higher in patients with lupus nephritis. The percentage of patients with high avidity antibodies was 87% in the group with renal involvement and 28% in the group with no kidneys involvement. Thus, lupus nephritis should be feared when anti-native DNA antibodies with high dissociation constant are found in the sera of SLE patients. PMID- 6240647 TI - [Lymphocyte subpopulations (T4-T8) in postoperative peritonitis]. PMID- 6240648 TI - [Iatrogenic femoral arteriovenous fistulas]. PMID- 6240649 TI - [Original technic of locoregional antibiotic prevention in abdominoperineal amputation of the rectum using gentamicin beads]. PMID- 6240650 TI - [Uselessness of Holter recording for the study of emboligenic cardiac arrhythmia after a cerebral ischemic accident of suspected emboligenic origin]. PMID- 6240651 TI - [Immunoglobulin A deposits in the dermal vessels in alcoholic hepatopathies]. PMID- 6240652 TI - [Microangiopathy and involvement of dermal connective tissue in young subjects with or without direct cardiovascular or diabetic antecedent]. PMID- 6240653 TI - [Intestinal pseudo-occlusion and treatment with cisplatin]. PMID- 6240654 TI - [Erythema annulare centrifugum in an infant. Effect of disodium cromoglycate in a drinkable solution]. PMID- 6240655 TI - [Monitoring diabetic nephropathy by the determination of microalbuminuria]. PMID- 6240656 TI - [Isoniazid inactivation in 2 ethnic groups]. PMID- 6240657 TI - [Rehabilitation of patients with chronic nonspecific diseases of the lungs at a rural outpatient clinic]. PMID- 6240658 TI - [Vocational rehabilitation of rural patients with tuberculosis in a sanatorium]. PMID- 6240659 TI - Some basic problems of proton-ATPase: chairman's introduction. PMID- 6240660 TI - On the structure and genetics of the proton-conducting F0 of the ATP synthase. PMID- 6240661 TI - Bacterial flagellar rotation and its chemotactic control. PMID- 6240662 TI - A review of clinical trials of lithium in neurology. AB - Lithium has been put to clinical trials in no less than fifteen neurological disorders. They are Huntington's chorea, tardive dyskinesia, spasmodic torticollis, Tourette's syndrome, L-dopa induced hyperkinesia and the "on-off" phenomenon in parkinsonism, organic brain disorders secondary to brain-injury, drug induced delusional disorders, migraine and cluster headache, periodic hypersomnolence, epilepsy, meniere's disease and periodic hypokalemic paralysis. This paper gives a brief summary of the clinical trials with lithium salts reported in the literature. There are encouraging results on the use of lithium in cluster headaches, cyclic form of migraine and hypomanic mood disorders due to organic brain disorders. The trials with lithium and amitriptyline in tardive dyskinesia needs independent confirmation. The effect of lithium on seizure disorders needs to be addressed too. PMID- 6240663 TI - Regeneration of rhodopsin and isorhodopsin in rod outer segment preparations: absence of effect of solvent parameters. AB - Regeneration of rhodopsin and isorhodopsin from bleached bovine rod outer segment suspensions and 11- or 9-cis retinal occurs at similar rates (second-order rate constants of 1000 M-1s-1 and 900 M-1s-1, respectively) and to a similar extent (maximal regeneration at pH 5.5-7.0). Formation of both pigments follows pseudo first order kinetics in an excess of retinal at pH 7.0. These results suggest that the mechanisms of regeneration are similar for the 11-cis and 9-cis retinal isomers. Solvent ionic strength, buffer concentration, viscosity, and polarity have no significant effect on the rate of pigment formation, providing further evidence that the retinal binding site in bleached bovine rod outer segments is well protected from the hydrophilic environment. PMID- 6240664 TI - Positron emission tomography of the brain: new possibilities for the investigation of human cerebral pathophysiology. AB - In the foregoing an overview of positron emission tomography has been presented. Its theoretical, technical, and methodological implications, as well as its clinical applications have been outlined. The emphasis has been on the quantitative aspects of the method and its usefulness is investigating normal and pathological functions of brain tissue. Although the potential of this new research technique is obvious, many theoretical and practical difficulties still need to be solved. Nevertheless it provides an opportunity to bridge the gap between basic experimental research and clinical medicine. PMID- 6240665 TI - Normal and abnormal determinants of dopamine receptor ontogeny in the central nervous system. PMID- 6240666 TI - Anti-phospholipase proteins. PMID- 6240667 TI - Identification of C3b as the major serum protein that stimulates prostaglandin and thromboxane synthesis by macrophages. AB - We have previously reported that heterologous, homologous and autologous sera, all stimulated rabbit alveolar macrophages to synthesize prostaglandins (PG). Gel permeation chromatography of serum showed multiple fractions possessing this stimulatory activity, with the major one at 150-160K daltons. In the present study, we have shown that: (a) Fresh rabbit serum stimulated PG release by macrophages. (b) Serum depleted of C3 and C5 lost its stimulatory activity. (c) Trypsinized serum, sera activated by aggregated IgG and zymosan, partially purified C3, C5 and the C3, C5 preparation or purified C3 activated by zymosan, all stimulated PG release by macrophages with the following order of potency: activated C3, C5 = activated C3 = zymosan-activated serum greater than trypsinized serum = aggregated IgG-activated serum greater than partially purified C3, C5 = serum. PGE2 was the predominant PG synthesized by stimulated macrophages. However, thromboxane (TX) production seemed to be more selectively enhanced i.e., increase in TX production was more pronounced than the increase in PGE release. To further identify the active complement component, we blocked the C3b receptor (C3 b R) by preincubating macrophages with anti-C3bR, and showed that subsequent treatment with activated C3 and C5 failed to elicit any PG release. This pretreatment with anti-C3bR had no inhibitory effect on subsequent zymosan stimulation of PG release. Thus we concluded that C3b was the major serum protein that stimulates PG synthesis by macrophages. PMID- 6240668 TI - [Contact allergy to the rubber cure accelerator, thiohexam]. PMID- 6240669 TI - [Malherbe's calcifying epithelioma of the skin of the arm at the site of Di-Per Te vaccination]. PMID- 6240670 TI - [Antiandrogens in dermatological therapy. I. Mechanism of action of antiandrogens with special reference to the skin]. PMID- 6240672 TI - [Our experience in the diagnosis and treatment of colorectal cancer]. PMID- 6240671 TI - Measurement of 24-hour whole-body retention of Tc-99mMDP with a thyroid uptake probe: quantitative assessment of metabolic and metastatic bone diseases. AB - A new method for the measurement of 24-hour whole-body retention (WBR) of Tc 99mMDP, using a thyroid uptake probe with a normal scintigraphic dose was established. Its clinical significance was evaluated in 106 subjects over 20 years old with various bone disorders, including metabolic and metastatic bone diseases. Reproducibility of 24-hour WBR in 10 patients was very good (y = x - 0.3, r = 0.996). The 24-hour WBR of Tc-99mMDP in healthy subjects was 30.4% +/- 4.6%. The WBR values for patients with chronic renal failure, metastatic bone disease, osteomalacia and hyperthyroidism were 98.4% +/- 3.0%, 44.0% +/- 8.0%, 50.7% +/- 2.8% and 39.4% +/- 6.5%, respectively, which were significantly higher when compared with the healthy group. However the WBR of the steroid-induced osteoporotic group was significantly lower (17.3% +/- 5.4%), suggesting the possibility of being able to differentiate osteoporotic patients from healthy subjects. For assessment of the value of 24-hour WBR, simultaneous bone imaging was essential so as to be able to exclude the effects of arthropathy and/or fracture, which were often found in the older age group. PMID- 6240674 TI - [Anastomotic procedure and reflux esophagitis following total and upper pole gastrectomies]. PMID- 6240673 TI - [Surgical risk to chronic liver patients]. PMID- 6240675 TI - [Complexity of the lesions in a case of biliary lithiasis]. PMID- 6240676 TI - [Stomach diverticula. Apropos 2 cases]. PMID- 6240677 TI - [Posttraumatic right-sided diaphragmatic hernia]. PMID- 6240678 TI - [Subarachnoid anesthesia with pethidine and the hierarchy of pain intensity]. PMID- 6240680 TI - [Diagnostic and treatment problems in acute cholecystitis]. PMID- 6240679 TI - [Consequences of using naloxone in morphine anesthesia]. PMID- 6240681 TI - [Diagnostic and treatment problems due to nonspecific inflammatory tumor of the colon]. PMID- 6240682 TI - [Paradoxical symptomatology of rupture of the lateral meniscus]. PMID- 6240683 TI - [Emboligenic risk of varicose thrombophlebitis]. PMID- 6240684 TI - [Emergency therapeutic solutions in cardiopericardial wounds]. PMID- 6240685 TI - [Osteosynthesis with an elastic rod as an alternative in treating fractures of the pelvic limb]. PMID- 6240686 TI - [Reflux gastritis after Soupault-Bucaille reconversion. A special surgical solution]. PMID- 6240688 TI - [Hepatic artery variants--surgical implications]. PMID- 6240689 TI - [Effect of halogenated inhalational anesthetics on human liver mitochondrial function]. PMID- 6240687 TI - [Cicatriceal stenosis of the terminal ileum, a rare complication of closed abdominal injury]. PMID- 6240690 TI - [Multiple synchronous cancers of the colon and rectum]. PMID- 6240691 TI - [Etiopathogenic and therapeutic aspects of peritonitis cases with delayed hospitalization]. PMID- 6240692 TI - [Anatomico-clinical and therapeutic aspects of colonic volvulus concomitant with volvulus of the small intestine]. PMID- 6240693 TI - [Diagnostic and treatment problems in traumatic ruptures of the parenchymatous abdominal organs (liver and spleen) in children]. PMID- 6240694 TI - [Indications for Zanoli's method in treating fractures of the tibial plateau]. PMID- 6240695 TI - [Septic complications secondary to radiation treatment in uterine neoplasms]. PMID- 6240696 TI - [Our experience in the combined treatment of thyroid cancer]. PMID- 6240697 TI - [Gardner syndrome associated with a periampullary tumor. Presentation of a case]. PMID- 6240698 TI - [Acute mitral insufficiency from bacterial endocarditis after cholecystectomy]. PMID- 6240699 TI - [Our experience in the therapy of pain]. PMID- 6240700 TI - [Radial keratotomy]. PMID- 6240701 TI - [Risk factors in central arterial occlusion of the retina]. PMID- 6240702 TI - [Terminal thrombotic glaucoma]. PMID- 6240703 TI - [Reparative surgical procedure in palpebral coloboma by a tarsal substitute with a teflon artificial artery]. PMID- 6240704 TI - [Our experience in the argon treatment of eye lesions]. PMID- 6240705 TI - [Posterior vitrectomy in nontraumatic vitreous hemorrhage]. PMID- 6240706 TI - [Use of the Francois technic in glaucoma and cataract]. PMID- 6240707 TI - [Instrument for the extraction of nonmagnetic intravitreous foreign bodies]. PMID- 6240708 TI - [Hypertensive uveitis. IV. Treatment]. PMID- 6240709 TI - [Intraocular foreign bodies. The experience of the Baia Mare Ophthalmology Section in treating nonmagnetic intraocular foreign bodies]. PMID- 6240710 TI - [Prophylactic iridectomy in closed-angle glaucoma]. PMID- 6240712 TI - [Chronic retinal venous obliteration in glaucoma]. PMID- 6240711 TI - [Spontaneously healed retinal detachment after the extraction of an undiagnosed intraocular foreign body]. PMID- 6240713 TI - [Current findings on auricular cholesteatoma]. PMID- 6240714 TI - [Our experience with surgery for cysts and fistulae of the thyroglossal tract]. PMID- 6240715 TI - [Current clinico-therapeutic findings in nasal polyps]. PMID- 6240716 TI - [Indications for surgical treatment and the choice of the operative procedure in chronic sphenoethmomaxillary sinusitis. A viewpoint]. PMID- 6240717 TI - [Rhinosinusitis in children. Clinical aspects and therapeutic features]. PMID- 6240718 TI - [Incidence of chronic suppurative otomastoid complications at the Coltea ENT Clinic in 1976-1980]. PMID- 6240719 TI - [Deafness and the radiologic aspect of the mastoid in chippers using pneumatic hammers on steel and iron castings]. PMID- 6240720 TI - [Bilateral cholesteatoma with the tympanum intact and bilateral facial paralysis]. PMID- 6240721 TI - [Malignant melanoma of the external auditory canal treated by cryotherapy]. PMID- 6240722 TI - [Spastic dysphonia]. PMID- 6240723 TI - [The risk of infection with hepatitis B virus in dentistry]. PMID- 6240724 TI - [Various observations on the procedures for polymerization of acrylic dentures and the impact of non-compliance]. PMID- 6240725 TI - [Indications for the examination of intermaxillary relations in the light of occlusal relations]. PMID- 6240727 TI - [The incidence of dentomaxillary anomalies in collectives of pre-school children]. PMID- 6240726 TI - [Activator appliances in the treatment of anomalies in the transverse plane]. PMID- 6240728 TI - [Dental changes in endocrine diseases]. PMID- 6240729 TI - [The Wunderer activator]. PMID- 6240730 TI - [The inhibitory effect of chlorhexidine digluconate on various enzyme activities in vitro]. PMID- 6240731 TI - [The bacteriostatic activity of Geranium species]. PMID- 6240732 TI - [A comparative study of the clinical, electrical and radiologic methods of measuring the length of root canals]. PMID- 6240733 TI - [Viscero-cranial dysmorphism and dento-periodontal dysmorphism in acromegalia]. PMID- 6240734 TI - [The concept of neuromuscular occlusion. II. The apparatus and its function]. PMID- 6240735 TI - [Aspects of treatment using semi-physiognomic bridges]. PMID- 6240737 TI - [10 years' activity, 10 courses dedicated to the continuous advancement of the cadre of specialists striving to improve the health status of the population in our country]. PMID- 6240736 TI - [Calcium, inorganic phosphates and nucleotides in the saliva of patients with periodontal diseases and gingivitis]. PMID- 6240739 TI - [Hyperthyroidism, Down's syndrome and ferropenic anemia]. PMID- 6240738 TI - [Contribution of laparoscopy and hepatic biopsy to the diagnosis of the fever-of unknown-origin syndrome]. PMID- 6240740 TI - [Percutaneous transluminal angioplasty in aortic coarctation in the adult]. PMID- 6240742 TI - Soluble suppressor of T cell proliferation in primary in vitro response to murine minor histocompatibility antigens. AB - Normal mouse lymphocytes are not capable of mounting a primary cytotoxic T cell response to Mls encoded, non H-2, allodeterminants, although a strong lymphoproliferative response is observed in primary MLR between Mls incompatible cells. In this study it is reported that in the supernatant of primary cultures between AKR macrophages and CBA/H lymphocytes (H-2 identical, incompatible for Mls and other minor antigens) a suppressor of T cell proliferation in MLR is detected. By contrast, a suppressor is not detected in supernatants from primary cultures between BALB/C macrophages and CBA/H lymphocytes (H-2 incompatible, Mls identical), B10.BR macrophages and CBA/H macrophages and CBA/H lymphocytes (syngeneic) suggesting that the production of the suppressor factor occurs only when an Mls incompatibility exists. The suppressive activity of the Mls incompatible culture supernatant upon MLR between incompatible macrophages and lymphocytes is neither antigen specific nor Mls or H-2 restricted, nor is it due to an irreversible toxic effect on T lymphocytes or macrophages. The inhibition of T cell proliferation could be explained by inhibition of IL 2 production, by blocking its union to T cells or by a combination of both effects. Our findings could help explain previous observations that lymphocytes from mice preimmunized with Mls incompatible cells have a depressed proliferative response as well as depressed cytotoxicity against alloantigens. PMID- 6240741 TI - [Quantification (by nomograms) of physiopathological parameters in an experimental model of passive anaphylaxis caused by immune complexes]. AB - Pharmacological changes in a model of passive anaphylaxis by immune complexes in mice have been studied. The results have been evaluated by nomograms to overcome the difficulties observed when using classical criteria as 50% lethal dosis or 50% infective dosis in experimental models which do not allow serial dilutions of the reagents. Mean lethal time, maximal pathogenic capacity and relative survival time can be easily determined, allowing the comparison of the immunopharmacologic protection for each administration schedule. By these criteria, we have observed a different degree of anaphylactic reaction depending on the genetic background of the hosts as well as a protection against anaphylactic shock using the antiserotoninic cyproheptadine and, to a lesser extent, by the platelet antiaggregant ticlopidine. PMID- 6240743 TI - [Dilatation and hypertrophy of cardiac cavities. Anatomo-electrocardiographic correlation]. PMID- 6240744 TI - [Dubin-Johnson syndrome. Enzyme histochemical study of the liver]. PMID- 6240745 TI - The economist and rehabilitation. PMID- 6240746 TI - Disability: the view from social policy. PMID- 6240747 TI - Reconceptualizing disability: a political science perspective. PMID- 6240748 TI - The phenomenology of disability: implications for vocational rehabilitation. PMID- 6240749 TI - [Effect of SCH 1000 on bronchial hyperreactivity compared to that of fenoterol]. AB - The hyperreactivity-modulating effect of SCH 1000 and fenoterol was tested in two groups of 10 patients. The drugs were administered at random, in simple blind fashion. Baseline pulmonary function was in the range of predicted values for all patients. One group received 80 micrograms of SCH 1000. When the drug was inhaled after carbachol challenge, pulmonary function returned to normal values in all patients. When the drug was inhaled before challenge, a shift to the right of the dose-effect curves was observed in all patients but 1. The other group received 800 micrograms of fenoterol. When the drug was administered after carbachol challenge, all 10 patients returned to baseline within 10 min. When it was given before carbachol challenge, a shift to the right of the dose-effect curves was observed in 9 patients out of 10. SCH 1000 and fenoterol induced an effective protection against carbachol, increasing the PD20 and shifting the dose-effect curves to the right in most of the asthmatics. In 2 patients, 80 micrograms of SCH 1000 or 800 micrograms of fenoterol seemed too low in order to achieve a complete protective effect. PMID- 6240750 TI - [The study of ideal patients for percutaneous transluminal coronary angioplasty]. PMID- 6240751 TI - Ventilatory responses and blood gases in susceptible and resistant rats to high altitude. AB - On exposure to a stimulated altitude of 5500 m (18 000 ft), the Hilltop (H) strain of Sprague-Dawley rats develops signs of chronic mountain sickness (CMS) (severe polycythemia, severe pulmonary hypertension and right ventricular hypertrophy) associated with a high mortality rate. In contrast, the Madison (M) strain of Sprague-Dawley rats remains healthy with less severe cardiopulmonary and hematological responses. We tested the hypothesis that hypoventilation in the H rats relative to the M rats, leading to greater alveolar hypoxia or hypoxemia, could account for the different hematological and cardiopulmonary responses between the two strains. Ventilatory responses and blood gases were compared under normoxia and acute and chronic hypoxia in fully awake and unrestrained animals of the two strains. There were no differences in VE, Pao2, PaCO2, pHa, P vO2, PvCO2 and pH-v under either acute or chronic hypoxia between the two strains of rats. It is concluded that relative hypoventilation does not contribute to altitude susceptibility in H rats. PMID- 6240752 TI - The role of pulmonary vascular responses to chronic hypoxia in the development of chronic mountain sickness in rats. AB - A strain of Sprague-Dawley rat obtained from Hilltop Labs, Scottsdale, PA (H rats), develops more severe pulmonary hypertension, right ventricular hypertrophy, and polycythemia than a strain obtained from Madison, WI (M rats), following exposure to simulated high altitude. We sought to determine whether differences in pulmonary vascular responses to chronic hypoxia could explain the differing high altitude susceptibilities of the two strains. Vasoconstrictor responses to hypoxia and angiotensin II were tested in blood perfused lungs isolated from rats of both groups exposed to stimulated high altitude (4 to 5 weeks, 0.5 atm), or from sea level controls. Pressure-flow curves, serving as an index of 'passive' vascular resistance, were also determined in the isolated lungs. Vasoconstrictor responses to hypoxia were blunted in high altitude rats of both the H and M strains compared to sea level controls, and the H sea level rats had blunted vasoconstrictor responses to hypoxia compared to the M sea level rats. Vasoconstrictor responses to angiotensin II were similar among the groups and were unaffected by chronic high altitude exposure. Pressure-flow curves were greater in both high altitude groups than in the sea level groups, and those of the H high altitude rats were slightly greater than those of the M high altitude rats. Thus, differences in vasoconstrictor responses to hypoxia do not explain the greater pulmonary hypertension of H high altitude rats. However, greater 'passive' vascular resistance, probably due to more extensive structural remodeling of pulmonary vessels, does appear to contribute to the greater pulmonary hypertension of the H rats. PMID- 6240753 TI - [Diphosphonates in the treatment of hypercalcemia]. AB - The diphosphonates (DP) represent a new class of therapeutic agents, the main property of which is to block bone resorption, irrespective of its stimulus. Apart from their remarkable results in Paget's disease of the bone, DP are very effective in the treatment of hypercalcaemia the osseus origin of which is nearly always essential. In malignant hypercalcaemia, EHDP, C12 MDP and APD, the three DP tested in man, cause a fall in serum calcium in a few days when administered intravenously. The latter two preparations are also effective when given orally. DP are also valuable in controlling hypercalcaemia in primary hyperparathyroidism. Research is under way to determine the role of DP in the prevention of malignant osteolysis, as distinct from the effects of chemotherapy. PMID- 6240754 TI - [Infrared spectra of dental restorative composite resins for posterior teeth and their bonding agents]. PMID- 6240755 TI - [Coronary thrombolysis in acute myocardial infarction]. AB - The effect of early perfusion after intracoronary infusion of urokinase (PTCR) in patients with acute myocardial infarction was assessed. Coronary perfusion was reestablished in 7 of 10 patients receiving intracoronary urokinase. We compared the recanalized group after intracoronary urokinase (n = 7) with the standard therapy group (n = 32). Left ventricular end-diastolic pressure, cardiac index, angiographic ejection fraction, radionuclide ejection fraction, defect score by Thallium-201 scintiscan and regional ejection fraction by the left ventriculogram, measured at about one month after the onset of acute myocardial infarction, were compared according to the site of the main coronary lesion (right coronary artery or left anterior descending coronary artery). No statistically significant differences between the recanalized group after the administration of intracoronary urokinase and the control group were found at each coronary lesion. On the other hand, the comparison between two patients with and without PTCR, who matched the clinical and coronary angiographic findings, showed that PTCR on acute myocardial infarction might be of value. However, evaluation of the long-term effects of coronary thrombolysis on survival and myocardial function will require controlled randomized trials of a large number of patients. PMID- 6240756 TI - Relationship between pathogenesis and immune regulation mechanisms in histoplasmosis: a hypothetical approach. AB - The cellular immune response may be the principal mechanism of defense against infection with Histoplasma capsulatum. Subsequently, regulation of cell-mediated immunity could be fundamental to the outcome of disease. Suppressive phenomena present in the host before infection or brought about by fungal components-would explain the various courses of infection. The fact that high titers of antibodies are associated with a poor cellular response suggests that antibodies may have a role as "regulatory molecules" in histoplasmosis. Antibodies may modulate the expression of the cellular response either by direct inhibition or by activation of the suppressor cell population, thereby interfering with the infectious process. PMID- 6240757 TI - The mammalian muscle spindle and its central control. PMID- 6240758 TI - Level of the A, B and H blood group glycosyltransferases in red cell membranes from patients with malignant hemopathies. AB - Eight patients (4 suffering from acute myeloid leukemia) exhibiting a loss of ABO red cell antigens, as seen by a mixed-field reaction pattern in agglutination tests, were selected and examined for the level of the A, -B, -H blood group glycosyltransferases within membranes prepared from erythrocyte subpopulations (A or B positive and A or B negative red cells). A or B enzyme activities were largely decreased in membranes which had lost A or B antigens (A or B negative subpopulations) but were within normal level in membrane from cells which had not lost A or B antigens (A or B positive subpopulations). The H enzyme level which was frequently low in the serum was within normal limits in the membrane preparations examined. Since A or B negative subpopulations were normally glycosylated in vitro into A or B reactive structures, the results demonstrate that loss of A or B antigens is related to some alteration of the blood group gene products rather than to significant abnormalities of the membrane precursors. PMID- 6240759 TI - [Handi village. A village unlike others. And after...where do I go?]. PMID- 6240760 TI - Congenital deficiencies in alpha 2-antiplasmin. PMID- 6240761 TI - Placental trophoblastic membrane surface receptors to some maternal plasma proteins. PMID- 6240762 TI - Recent progresses in the phenotypic and functional characterization of human cytolytic T lymphocytes. AB - Over the past several years, a number of major advances have been made in our understanding of the phenotypic and functional heterogeneity of human T lymphocytes. Most of these advances have resulted from: 1. the availability of monoclonal antibodies directed to T cell surface antigens; 2. the development of sensitive microassays to measure lymphocyte function in vitro; 3. the refining of T cell cloning technology. The most relevant studies in delineating how human T cell functions have been based on the analysis of T cell clones with specific cytolytic activity. These studies allowed the recent molecular definition of structures serving as specific antigen receptor on T cells as well as the understanding of the role of accessory molecules involved in specific receptor activity such as T3, T8 and T4 antigens. The development of microculture conditions allowing clonal proliferation of all human T lymphocytes, whether resting or activated, has provided a major tool for the precise definition of the frequency and subset distribution of T cells with different functional capabilities. Studies along this line have shown that precursors of cytolytic T lymphocytes (CTL-P) represent about one third of peripheral blood human T lymphocytes; in addition, all T8+ were CTL-P, whereas CTL-P were relatively rare among normal T4+ lymphocytes. As much as 20% cytolytic T lymphocytes were found to be capable to release interleukin-2 and B cell growth factor, thus indicating that cytolytic and helper function may be associated at the single cell level. PMID- 6240763 TI - Alterations of both responder T cells and stimulator non-T cells are responsible for abnormal mixed lymphocyte reaction in aged humans. AB - The autologous and allogeneic mixed lymphocyte reactions of 15 young and 15 aged human adults were compared. Both autologous and allogeneic mixed lymphocyte reactions were significantly reduced in the aged group. T cells from aged adults displayed a reduced proliferative response to non-T cells of either aged or young adults. T cells from young adults also showed a reduced proliferative response to non-T cells from aged adults. Sera from aged adults, showing depression of autologous and allogeneic mixed lymphocyte reaction, did not exert any inhibitory effect on the autologous and allogeneic mixed reaction of lymphocytes from young donors. These data suggest that depression of mixed lymphocyte reaction in aged humans probably reflects intrinsic abnormalities of both responder T cells and stimulatory non-T cells. PMID- 6240764 TI - Effect of ipratropium bromide on nasal mucociliary transport. AB - Ipratropium bromide is a parasympatholytic drug. After application to the nose, the nasal mucociliary transport time was measured using the method of the saccharin test. This compound did not cause any changes in the nasal mucociliary transport function. PMID- 6240765 TI - Determination of urinary mucopolysaccharides in Graves' disease. AB - Urinary mucopolysaccharides (u MPZ) were determined in 114 patients with thyroid diseases. The values were elevated in 95.8% of patients with Graves' disease with infiltrative ophthalmopathy, and in 66.6% of patients with Graves' disease without clinically manifest infiltrative ophthalmopathy; in the second group of patients we consider that there is a subclinical infiltrative ophthalmopathy. In conclusion, the determination of u MPZ can be considered as a criterion for the diagnosis of Graves' disease in patients with hyperthyroidism without clinically manifest infiltrative ophthalmopathy; in a number of these cases, infiltrative ophthalmopathy may become clinically manifest. For that reason, increased u MPZ can represent a criterion for an eventual delay of an ablative therapy in Graves' disease. It is not a significant statistic difference (p greater than 0.1) between the values of u MPZ in patients with Graves' disease with clinically manifest ophthalmopathy and in those with subclinical infiltrative ophthalmopathy. The thyroid functional status does not influence in any way the values of u MPZ (p greater than 0.1). There is no correlation between the degree of eye protrusion and the values of u MPZ (r = = -0.05) PMID- 6240766 TI - Note on the pathology of the basal nucleus of Meynert in degenerative brain disorders. PMID- 6240767 TI - [Abdominal wall hematoma as a severe complication of anticoagulation. Clinical picture and ultrasonic diagnosis]. AB - In 4 women patients aged over 60 years under anticoagulation, abdominal pain, which was in part clearly localizable, and signs of acute bleeding suddenly occurred. All were under treatment with marcoumar, while one was also in the transitional phase from parenteral to oral therapy with heparin. Initially, apart from pain on pressure, there were no local signs of bleeding. In the acute stage it was impossible to distinguish clinically between abdominal wall bleeding and intraperitoneal bleeding. Ultrasound provided the diagnosis of abdominal wall bleeding in all cases. All of them were successfully treated by conservative means. PMID- 6240768 TI - [Echocardiographic follow-up study of former top athletes with typical sports heart]. PMID- 6240769 TI - Current cutaneous drug reaction patterns in Singapore. PMID- 6240771 TI - Age and capacity devaluation: a replication. AB - This study replicates and extends an earlier study of disabled men based on 1966 national survey data which supported the hypothesis of capacity devaluation among older persons who considered themselves disabled, by finding that age was related to self-reported severity of work disability independent of several measures of functional capacity loss and prior job requirements. We analyzed data from a 1972 national survey of disabled persons in the U.S. aged 20-64 for women as well as men, utilizing more comprehensive and direct measures of capacity loss and prior work situation. Cross-tabular and logit analyses largely confirm the finding in the earlier study and extend them to disabled women: age independently affected self-perceived severity of work disability. Capacity devaluation among the near aged occurred particularly among less incapacitated blue-collar men but its occurrence was not greater among those with more specific exertional requirements in the prior job. The results generally support the conclusion that older persons with work limitations devalue their residual capacities for work. Older persons' evaluations of their work abilities appear to be influenced by social expectations of declining capacities with age and by social sanctions permitting premature withdrawal from work for reasons of health. PMID- 6240770 TI - Disabled persons in Poland. AB - It is generally considered that disability is an important social problem. This was expressed for example by the decision of the United Nations Organisation to nominate 1981 as the International Year of the Disabled. The number of disabled is one of the main problems. For social planning, the proper allocation of goods and resources for changes in the attitudes of society towards disability it is necessary to identify the prevalence, distribution and composition of the disabled. Prior to the 1978 Census, in Poland there was no information available on disability except the number of disabled persons legally classified by the Medical Board for Disability and Employment receiving disability pension, as well as the average amount of such pension, the number of disability certificates issued annually, the number of employed and the number employed in co-operatives for the disabled. The social criterion--major social role associated with psycho physical state--was the main concept of the investigation on the frequency of disability in 1978 Census. Methodology used in this study of disability was based on the U.S. experience gained from the 1970 NC, as well as on the NCHS Survey of psychophysical causes of permanent limitation of social role performance and locomotion, performed since 1957. It should be explained, however, that the scope of disability investigated in NCHS Survey and in Polish Census is exactly the same and much wider than in U.S. Censuses. The Polish National Census revealed that there are 2,485,001 disabled persons in Poland, i.e. 7.1% of the total population. The urban population constituted 57.7% and the inhabitants of rural areas 42.5% of the total population.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 6240772 TI - [Selection of workers at a factory sanatorium]. PMID- 6240773 TI - [Features of children's perception of the hospital environment (deontologic and psychological aspects]. PMID- 6240774 TI - [Improving the health status of medical students]. PMID- 6240775 TI - [Improvement in medico-sanitary services to cattle-breeders on the range]. PMID- 6240776 TI - [150th anniversary of the 1st children's hospital in Russia]. PMID- 6240777 TI - [Development of Soviet public health in the Uzbek SSR (on the 60th anniversary of the formation of the UzSSR)]. PMID- 6240778 TI - [Increasing the efficiency of the hospital bed supply]. PMID- 6240779 TI - [Duration of patient stay in a department of intensive therapy and resuscitation]. PMID- 6240780 TI - [Consultative-diagnostic services of medical school specialists]. PMID- 6240781 TI - [Organization of socialist competition in a specialized hospital]. PMID- 6240782 TI - [Materials on the history of the sanitary organization of the Lower Volga Region]. PMID- 6240783 TI - [Realization of the research target program on the problem of "lung cancer" in the RSFSR]. PMID- 6240784 TI - Introductory address: gonorrhea today. AB - The counterattack to the resurgence of one of the commonest infectious diseases, gonorrhea, still consists of epidemiologic measures, correct clinical and microbiological diagnosis, and effective treatment. Few antibiotics effective against Neisseria gonorrhoeae fulfill the criteria of the World Health Organization (i.e., the antibiotic should be effective, safe, free from side effects, capable of aborting simultaneously acquired or coexisting infection with Treponema pallidum or Chlamydia trachomatis, should entail a low incidence of postgonococcal urethritis, and should not be the sole antibiotic used for other, more serious conditions). Therefore, current attention is focused on the use of thiamphenicol for the treatment of uncomplicated urogenital, rectal, and oropharyngeal gonorrhea caused by both beta-lactamase-producing and non-beta lactamase-producing Neisseria gonorrhoeae. PMID- 6240785 TI - Thiamphenicol in the treatment of gonococcal infections: a comparative trial with penicillin and spectinomycin. AB - The efficacy of thiamphenicol for treatment of uncomplicated gonococcal infection was compared with that of penicillin and spectinomycin in 370 women confined in the clinic to preclude reinfection before evaluation of treatment. Thiamphenicol (2.5 g perorally) was highly effective against beta-lactamase-producing Neisseria gonorrhoeae, but the failure rate in infections with non-beta-lactamase-producing N. gonorrhoeae was high. This rate was not, however, significantly higher than that for beta-lactamase-producing strains. The failure rate with thiamphenicol was significantly higher than that with spectinomycin (2 g im) in the treatment of infections due to beta-lactamase-producing N. gonorrhoeae but was essentially similar to that observed with aqueous procaine penicillin G (4.8 X 10(6) units im) plus probenecid (1 g perorally) among non-beta-lactamase-producing N. gonorrhoeae. Therefore thiamphenicol may be used as an alternative therapy for gonorrhea, especially for infections due to beta-lactamase-producing strains. PMID- 6240786 TI - Comparison of thiamphenicol and spectinomycin in the treatment of uncomplicated gonorrhea in men. AB - Thiamphenicol (2.5 g perorally) was compared with spectinomycin (2.0 g im) in the treatment of uncomplicated gonococcal urethritis in men. Patients were selected on the basis of cultures positive for Neisseria gonorrhoeae and were randomly assigned to one of the treatment regimens. Test-of-cure cultures were done three to five days after treatment. Beta-lactamase activity of every isolate was tested. In the group treated with thiamphenicol, 152 patients were followed; 63 (41.4%) failed to be cured, while the spectinomycin regimen gave a cure rate of greater than 95%. Penicillinase-producing strains gave a greater rate of failure than non-penicillinase-producing strains. The strains of N. gonorrhoeae isolated in Seoul had high minimal inhibitory concentrations of various antibiotics. About 48% of strains had a MIC of greater than or equal to 2 micrograms of thiamphenicol/ml. Hematologic examinations, repeated on days 0, 3-5, 10, and 30 of treatment, revealed no appreciable toxicity following the thiamphenicol regimen. PMID- 6240787 TI - Single-dose treatment of uncomplicated gonorrhea in men with intramuscular and oral thiamphenicol. AB - Each of 200 men with uncomplicated gonococcal urethritis was randomly assigned to a group receiving one of two therapeutic regimens. Group A received 2 g of spectinomycin intramuscularly. Group B received 2.5 g of thiamphenicol, with 500 mg administered intramuscularly just after oral administration of 2 g. Of the 89 patients in group A who completed the study, 32 were infected with penicillinase producing Neisseria gonorrhoeae, 49 with non-penicillinase-producing N. gonorrhoeae, and eight with gonococcal strains not tested for penicillinase production. Infection was cured in all 89 patients. Of the 91 patients in group B who completed the study, 33 were infected with penicillinase-producing N. gonorrhoeae, 54 with non-penicillinase-producing N. gonorrhoeae, and four with gonococcal strains not tested for penicillinase production. Infection was cured in 86 (94.5%) of the 91 patients. Thus, the single-dose regimen of thiamphenicol was effective against uncomplicated infections caused by either penicillinase producing or non-penicillinase-producing strains of N. gonorrhoeae. PMID- 6240788 TI - [Dental care for the bed-ridden aged]. PMID- 6240789 TI - [Compositions of various visible light-cured composite resins and elutions of residual monomer from these cured resins]. PMID- 6240790 TI - [Role of the hereditary factor in the genesis of chronic bronchitis]. AB - Comparison of proband concordance of the phenotypic correlation coefficients according to the proneness to disease derived on analysis of the groups of mono- and dizygote twins born in 1930-1959 in the city of Yerevan presenting with chronic non-obstructive and chronic obstructive bronchitis revealed a substantial role of hereditary factors in the development of these patterns of chronic bronchitis. The inheritance coefficients calculated on the basis of the data obtained for chronic non-obstructive and chronic obstructive bronchitis point to the contribution of genetic factors to chronic bronchitis proneness among the population of the city of Yerevan. PMID- 6240791 TI - [Interrelation of autoimmune and immune complex pathology: the current status of the problem]. PMID- 6240792 TI - [Obesity as a current social problem]. AB - The increasing prevalence of overweight and obesity, the classification of the population whose age is the most favourable for working activities as patients, considerable prevalence of the disease among children and young people, the disease progress and severe complications make obesity one of the most important problems today. The development of obesity and complications is mainly caused by energy imbalance which gets aggravated in subjects manifesting lipid metabolism pathology. Disorders in the character and rhythm of nutrition are most remarkable in cases of obesity complicated by cardiovascular pathology, diseases of the hepatobiliary system, diabetes mellitus, and so forth. Taking into consideration the significance of the problem of obesity the Institute of Nutrition, Academy of Medical Sciences of the USSR, developed a program of measures whose realization will favour the solution of the Food Program. PMID- 6240793 TI - [Correlations between nonspecific suppressor activity of mononuclear cells and IgE levels in patients with pollinosis]. AB - The total IgE level and some indicators of nonspecific suppressor activity (NSA) (the amount of theophylline-sensitive sells and the activity of Con A-induced spontaneous and short-lived suppressors) were studied in 36 pollinosis patients with high sensitivity to timothy dust, confirmed by the data of the allergological anamnesis, the data of skin and provocative tests with timothy allergen, and by the presence of allergen-specific IgE antibodies. The IgE level ranged from 23 to 2925 KU/1. Preincubation of mononuclear cells with theophylline did not lead to a significant diminution of the number of E-RFC. The majority of patients demonstrated the activity of all the above-indicated suppressors upon the use of mitogens at several concentrations. Correlation of the NSA with the IgE magnitudes showed disagreement in all the cases with the exception of the test with short-lived suppressors (a variant of the test culture with Con A) where in one group of patients (11 examinees), a direct relationship was found, whereas in the other one (10 examinees), a reverse relationship. It is concluded that the test forms of NSA of lymphoid cells do not play an essential role in the maintenance of the total IgE level in pollinosis patients. PMID- 6240794 TI - [Creative legacy of N.S. Molchanov in the field of pulmonology (on his 85th birthday)]. PMID- 6240795 TI - [Complex medical rehabilitation of patients with rheumatic heart disease at the sanatorium stage using radon baths from a local source and homologous immunoglobulin]. AB - The paper discusses the efficacy of rehabilitation of 108 patients with rheumatic fever with the use of radon baths, of them in 36 in conjunction with homologous immunoglobulin. The patients were treated in a local balneological hospital. Balneotherapy has been shown to have a beneficial effect on the humoral and cellular immune response, and on factors of the body non-specific resistance in patients with unstable clinicolaboratory characteristics after the treatment for protracted rheumocarditis with minimal activity and latent course. The number of relapses and intercurrent infections were found to be decreased, and the working ability to be improved. The most pronounced effect was recorded in a group of patients who received radon baths and homologous immunoglobulin. PMID- 6240796 TI - [ECG characteristics in patients with idiopathic hypertrophic subaortic stenosis]. AB - The ECG data on 111 patients aged 2-61 years with idiopathic hypertrophic subaortal stenosis are provided. Of these, 18 patients were examined over time (during 1 to 6 years). The ECG data were considered depending on the clinical disease progress, the patients' age, and the intracardiac and echocardiographic findings. PMID- 6240797 TI - [The cardiovascular system in patients with chronic renal failure (echocardiographic data)]. AB - Based on the study of the echocardiography data in 44 patients with chronic renal failure it has been shown that the incidence and the degree of left ventricle hypertrophy is related to the duration of arterial hypertension, increased cardiac output, and metabolic abnormalities. Echocardiographic studies made over time revealed a progressive deterioration of myocardial contractility. Pericarditis that ensues promotes the deterioration of left ventricle contractility and aggravates heart insufficiency. The diastolic murmur of aortal regurgitation should be differentiated as pertaining to infectious endocarditis or to relative insufficiency of the aortal valve. Two-dimensional echocardiography favours differentiation of left ventricle myocardial hypertrophy, makes it possible to locate the fluid in the pericardium more accurately, and to evaluate the treatment efficacy for pericarditis. PMID- 6240798 TI - [Contact allergy in chronic venous insufficiency: therapeutic consequences from the dermatologic viewpoint]. PMID- 6240799 TI - [Immunological aspects of drug exanthema]. PMID- 6240800 TI - Fractionation and characterization of urinary heparan sulfate excreted by patients with Sanfilippo syndrome. AB - Urinary heparan sulfates (HS) from two siblings with mucopolysaccharidosis (MPS) III-B were fractionated by chromatography with Dowex 1 and Sephadex G-50. Their Mr ranged from 1600 to 8000, and 95% of them were included in the region less than 5000. Fractions with lower Mr contained larger amounts of O-and N-sulfates. The chemical analysis and deaminative cleavage of HS suggested that an intact HS molecule was composed of some blocks rich in GlcNAc and GlcUA and other blocks rich in GlcNS, IdUA and O-sulfate. GlcNAc-UA-GlcNS-UA-GlcNAc-UA-GlcNAc was found to be a major oligosaccharide of HS with Mr less than 1800. Trisaccharides, GlcNAc-GlcUA-aMan and GlcNAc-IdUA-aMan, were released from the nonreducing end of HS-oligosaccharides by deaminative cleavage. They carried 0-3 moles of ester sulfate. GlcNAc-IdUA-aMan was more sulfated than the other. The release of significant amounts of nonsulfated trisaccharide conform to the enzyme defect in this disease. Urinary HS obtained from another patient with MPS III were examined by the same way. Although the patient was not examined enzymatically, the structure of urinary GAG suggested a defect of alpha-N-acetylglucosaminidase in the patient. PMID- 6240801 TI - Androgen and FSH synergistically stimulate lipoprotein degradation and utilization by ovary granulosa cells. AB - Androgen can directly modulate the induction of steroidogenic enzymes by FSH (follicle stimulating hormone) in ovary granulosa cells. In studies of its mechanism of action, we examined the androgen effect on granulosa cell interaction with lipoproteins, the physiologic source of cholesterol. After granulosa cells were cultured for 48 hours with and without androgen and/or FSH, the cells were incubated for 24 hours with 125I-lipoproteins [human high density lipoprotein (HDL), rat HDL, or human low density lipoprotein (LDL)]. The media were then analyzed for lipoprotein protein coat degradation products (mainly 125I monoiodotyrosine) and progestin [mainly 20 alpha-dihydroprogesterone (20 alpha DHP)]. In the absence of FSH and androgen, 2 X 10(5) granulosa cells degraded basal levels of all three lipoproteins, but produced no measurable 20 alpha-DHP. The addition of 10(-7) M androstenedione (A), testosterone (T), or 5 alpha dihydrotestosterone (DHT) had no effect on lipoprotein protein degradation or 20 alpha-DHP production. FSH alone stimulated lipoprotein protein degradation by 50 to 300% while the addition of androgen synergistically augmented the FSH stimulated 20 alpha-DHP production as well as protein coat degradation of all three lipoproteins. DHT and T were both effective, indicating that androgens themselves, and not estrogen products, were responsible for the effect on lipoprotein protein degradation and 20 alpha-DHP production. The addition of a 10 fold excess cyproterone acetate (an anti-androgen) inhibited the effect of T, suggesting that the action of T was mediated by the granulosa cell androgen receptor. Androgen and FSH also synergistically stimulated the production of 3H progestin when the granulosa cells were incubated with either 3H-cholesterol ester core labeled human HDL or similarly labeled human LDL. This report demonstrates that androgen, in combination with FSH, augments the steroidogenic pathway of the granulosa cell from the degradation of lipoprotein and utilization of the cholesterol ester core, to the production of progestin product. PMID- 6240802 TI - Plasma levels of levonorgestrel, gestodene, norethisterone and cyproterone acetate on single-dose subcutaneous administration in oily solution in the rat, beagle and rhesus monkey. AB - This report describes the pharmacokinetics of levonorgestrel, gestodene, norethisterone and cyproterone acetate following subcutaneous administration of oily solutions in the rat, beagle dog and rhesus monkey. The plasma levels of the progestogens were measured by means of specific radioimmunoassays. Half-lives calculated for the disposition process of a particular metabolically unchanged drug in plasma revealed marked differences in different animal species. Furthermore, comparison of the different progestogens showed large variations in this parameter in all the animal species. It became obvious that there are physico-chemical properties as well as metabolic rate limitations effecting the release and elimination of synthetic progestogens administered in oily solution. The results are compared with the half-lives of these progestogens administered intravenously as reported previously. A prolongation of half-life as a result of the depot effect of subcutaneous administration was demonstrated for all the progestogens in the rat, the beagle dog and the rhesus monkey. PMID- 6240804 TI - [The beginnings of organic chemistry and today's neo-vitalism. On the 100th anniversary of Friedrich Wohler's death on 23 September 1982]. PMID- 6240803 TI - Early steroid metabolism by chick blastoderm in vitro. AB - Yolk free blastoderms of chick embryo were incubated 3 or 22 hours with labeled pregnenolone, progesterone, 17-hydroxyprogesterone, dehydroepiandrosterone, androstenedione, testosterone and estradiol-17 beta. Metabolites and unconverted substrates were found both in the incubation medium and in the cells. Enzymes responsible for identified conversions were: 17 alpha-hydroxylase, 17-20 desmolase, delta 5 3 beta- and 3 alpha-hydroxysteroid dehydrogenase, 17 beta hydroxysteroid dehydrogenase and 5 alpha- and 5 beta-reductase. The results suggest that the steroid metabolizing enzyme activities found may reflect a more general ability of early embryonic cells. PMID- 6240805 TI - [Suggestion and its significance in the history of medicine]. PMID- 6240806 TI - [Constraint--delusion--depression--melancholy: decomposition of normal ways of existence]. PMID- 6240807 TI - [Pettenkofer's theory of health economics, a milestone in the development of public health services]. PMID- 6240808 TI - [Do we need bio-ethics?]. PMID- 6240809 TI - [Awareness of history in the medicine of the Age of Romanticism]. PMID- 6240810 TI - [Homo patiens. On medical anthropology of sorrow and compassion]. PMID- 6240811 TI - [The structure of living matter. Novalis' "Fragments on Physiology"]. PMID- 6240812 TI - Being healthy down through history. PMID- 6240813 TI - [Ethics and medical thinking in the Arabic Middle Ages]. PMID- 6240814 TI - ["A word on the effect of the scientific museum on humane education" (G. A. Goldfuss 1821)]. PMID- 6240815 TI - [The public hospital as a scientific educational institution. Karl Wilhelm Stark (1787-1845) and his first plans for an academic teaching hospital from the year 1839--claims and reality]. PMID- 6240816 TI - [The historical as a principle in medicine]. PMID- 6240817 TI - [Basic tenets in Karl Jaspers' psychiatric practice]. PMID- 6240818 TI - Morphological identification of simulium sanctipauli and S. yahense in Liberia and comparison of results with those of enzyme electrophoresis. AB - Simulium sanctipauli and S. yahense have been incriminated as the main vectors of Onchocerca volvulus in the rain-forest zone of Liberia. An accurate identification of the females of the two species which breed in different types of water-courses but are morphologically similar is essential for a proper study of their epidemiological importance and the planning of control measures. Various external characters were examined for their diagnostic value by the comparison of identifications using these characters and those based on enzyme electrophoresis (phosphoglucomutase, trehalase). It was shown that the females of the two species can be separated reliably by the use of external morphological characters. The occasional finding in the same fly of phosphoglucomutase variants typical for each species indicated the possible occurrence of natural hybridization between S. sanctipauli and S. yahense. PMID- 6240819 TI - Characterization of the inflammatory cells in progressing tumor-like alveolar hydatid cyst. 2. Cell surface receptors, endocytosed immune complexes and lysosomal enzyme content. AB - Alveolar hydatid cysts (LCM) grow progressively and contribute significantly to the morbidity of hydatid-hosts. To examine whether modifications in immune effector parameters correlate with the pattern of LCM growth, in vivo experiments were carried out in C57BL/6J mice infected intraperitoneally with LCM. Immigrant peritoneal and intra-LCM leukocytes were tested for the loss of cell surface receptors, membrane-bound and internalized immune complexes (ICs) and lysosomal enzyme contents during the restrictive and progressive growth phases of the LCM. The proportion of Fc and C3b receptor-bearing intra-LCM leukocytes decreased 2 fold and 31 to 72% of the leukocytes contained ICs during the progressive phase of the LCM. Acid phosphatase and beta-glucuronidase activities of macrophages declined sharply during the restrictive phase but they gradually increased as the infection progressed. IC-mediated dysfunction of effector leukocytes and modulation of antibody dependent cell cystolysis mechanism are discussed in murine hydatidosis. PMID- 6240820 TI - [Removal of nitrous oxide from delivery rooms]. PMID- 6240821 TI - Distribution of ciprofloxacin in the dog prostate and various tissues. AB - The distribution in the dog prostate and other tissues of ciprofloxacin, a quinoline carboxylic acid derivative, was investigated in an experimental model. The concentrations in prostatic tissue, prostatic interstitial fluid (PIF), and prostatic secretion (PS) were lower than the corresponding plasma (P) concentrations, as would be expected for an acidic compound. The experiments were carried out under steady state conditions during intravenous infusion in one group of dogs and following gastric administration in another group. During steady state the ciprofloxacin concentrations were significantly higher in PS than in PIF, and the median PS/P ratios were significantly higher than the PIF/P ratios. These concentrations and ratios were compared with those of two other quinoline carboxylic acid derivatives, rosoxacin and norfloxacin. The concentrations of ciprofloxacin in prostatic tissue, PIF, PS, and urine were several times higher than the minimum inhibitory concentrations for most gram negative pathogens that cause bacterial prostatitis and urinary tract infections. Clinical trials of ciprofloxacin in these diseases are therefore indicated. PMID- 6240822 TI - [Remote results of the treatment of patients with adhesions in the abdominal cavity]. AB - 149 patients were operated upon for the adhesive process in the abdominal cavity. The antirecidivation treatment was performed after operation (intraperitoneal injection of prolonged proteolytic enzymes with hydrocortisone, trypsin electrophoresis). The enzyme therapy was associated with the antiinflammatory and antiallergic treatment. Long-term results were studied in 93 patients within the period from 2 to 10 years. Good results were obtained in 77% of the patients. PMID- 6240823 TI - Induction of intradermal skin reactions in the bovine by fractionated proteins of Hypoderma lineatum. AB - Protein species found in crude extracts of Hypoderma lineatum (Villers) 1st instar gullet-stage larval homogenates were fractionated by chromatography and further identified by conventional polyacrylamide gel electrophoresis (PAGE) and SDS/PAGE techniques. Seven major fractions were resolved by ion exchange chromatography. Conventional PAGE of the crude antigen preparation revealed a minimum of 14 protein species, while SDS/PAGE revealed 3 major protein species. The ability to elicit cutaneous reactivity by isolated proteins was determined by the intradermal skin test. An immediate-type hypersensitivity reaction was elicited in the skin of vaccinated and previously infested animals by the components of the 4 protein fractions tested. Only one protein fraction, fraction 4, elicited an apparent delayed reaction at 48 h in vaccinated and previously infested animals. A non-specific background reaction was elicited in control animals by the fractionated proteins and was most notable between 1- and 4-h post injection. PMID- 6240824 TI - [Radon steam bath therapy of patients with stage IIB hypertension at the Khodzha Obi-Garm health resort]. PMID- 6240825 TI - [Treatment of patients with ischemic heart disease and concomitant duodenal ulcer at the Dzhermuk health resort]. PMID- 6240827 TI - [Results and prospects of development of scientific research at the Kazakh Division, Institute of Nutrition, U.S.S.R. Academy of Medical Sciences]. PMID- 6240826 TI - [Metal content of food products from different regions of the country]. PMID- 6240828 TI - [Experience with the complex operation of public health and social service organs and institutions in preventing and reducing disability]. PMID- 6240829 TI - [Therapeutic plasmapheresis (review of the literature)]. PMID- 6240830 TI - [Case of cholecystocutaneous fistula]. PMID- 6240831 TI - [Treatment of hypertensive hyperuricemic patients with a new beta blocker diuretic combination]. AB - The antihypertensive activity of two fixed beta-blocker combinations was compared in a randomized double-blind study. 18 patients with degree I or II hypertension and hyperuricaemia were treated with a once daily dose for 4 weeks. 9 patients received 200 mg celiprolol. HCl +25 mg chlorthalidone, and 9 patients were treated with 100 mg atenolol + 25 mg chlorthalidone. Both substances produced a similar reduction in blood pressure and heart rate. There was a significant rise in the serum uric acid level in both treatment groups. PMID- 6240832 TI - Women with disabling health conditions: the significance of employment. AB - This study investigated employment status, desire to return to work, and health outlook among 148 women and 184 men with major disabling health conditions. Disabled women's need for job retraining and the importance of improved employer education about disability were recurrent themes during the interviews. No significant differences were found in women's and men's return to work or in desire for job retraining following disability onset. Perceived health status was significantly higher among employed women than among non-employed women, and the data suggest that employment contributes to improved health outlook among disabled women. PMID- 6240833 TI - Immunosuppression following excision of burn eschar and syngeneic grafting in major thermal trauma. AB - Recent reports have suggested that very early excision (less than 24 hours post burn) and primary closure of burn wounds might circumvent the immunosuppression which follows severe thermal trauma. The total body surface are (TBSA) involved in burn injuries of human subjects at risk for significant post-burn immunosuppression is large enough to require grafting. In the present study cell mediated immunity was measured via one-way allogeneic mixed lymphocyte reactions (MLR) in mice subjected to full-thickness scald wounds over 25-30 percent TBSA followed by escharectomy and syngeneic full-thickness skin grafting. A significant decrease in the proliferative capability of T-cells could be demonstrated on days five and seven post-treatment in unburned grafted animals (day five, 30.7 percent; day seven, 24.8 percent) over untreated normals. T-cells from animals burned but not excised also showed significant hyporesponsiveness (day five, 33.2 percent; day seven, 26.1 percent normal MLR). Animals undergoing both burning and excision showed even more profound immunosuppression (day five, 18.3 percent to 23.7 percent; day seven, 7.4 percent to 11.6 percent normal MLR). Surgical incision without excising the skin did not suppress cell-mediated immunity (day five, 90.8 percent; day seven, 90.4 percent normal MLR). When T cells from treated animals of each group (with the exception of the incision control group) were added to normal MLR cultures, significant (greater than 50 percent) cell-mediated suppression by suppressor T-cells could be demonstrated. This study showed that the trauma of excision and grafting alone results in depression of cell-mediated immunity. These data call into question the ability of very early excision and grafting to alter the immunosuppression which follows severe thermal trauma. PMID- 6240834 TI - [Current diagnostic value of laparoscopy]. PMID- 6240835 TI - [A rehabilitation complex--the hotel station. An ambulatory rehabilitation program for very severely disabled persons]. PMID- 6240836 TI - [Use of a special mechanization device--possibilities for patients with decreased efficiency and for rehabilitation patients]. PMID- 6240837 TI - [Etiopathogenetic aspects of psoriatic arthritis with special reference to immunologic factors]. AB - On 21 patients with psoriasis and 22 with psoriatric arthritis examinations for the recognition of the immune regulation were performed and the results were compared with those of healthy control persons and patients with rheumatoid arthritis. The psoriatric arthritis shows humoral as well as cellular disturbances of immune regulations which in the group comparison with the psoriasis and the rheumatoid arthritis partly have communities, but partly also have differences. With regard to size and distinction of the disturbances the patients with rheumatoid arthritis have the highest degree of severity. With the help of the techniques used by us systemic cellular disturbances of the immune regulations could not be proved in the psoriasis. The psoriatic arthritis to a certain extent occupies a medium position. But a clear coordination of these disturbances into the pathogenetic process is not yet possible. PMID- 6240838 TI - [Lymphocyte subpopulations in psoriatic arthritis]. AB - 17 and 20 patients, respectively, with psoriasis-arthritis were examined by means of the SE-, ME-, EA- and stable rosette test and the results were compared with the results in healthy control persons. In these cases in the patients with psoriasis-arthritis a significant increase of the B-cells carrying the ME receptor was objectified. This result is explained in the sense of an antigen stimulation. PMID- 6240839 TI - [Current findings on drug eruptions]. AB - Drug eruptions are the result of a systemic application of medicaments. They depend on immunologic and non-immunologic mechanisms. With the exception of a few medicaments, skin tests with drugs are not very reliable. Patch-tests may only be recommended with regard to a macular or a maculo-papular rash, because cell mediated immunologic mechanisms are involved. The most valuable in vitro test is still the lymphocyte transformation test. New in vitro test procedures, e.g. based on lymphokines, are under investigation. Regarding the clinical practice, drug eruptions brought about by antibiotics, cytostatics, modern anti-rheumatics and anti-inflammatory agents, some psychotropics, as well as newer cardiovascular drugs are of special interest. All these important groups of drugs are constantly expanding. Thus the dermatologist has to reckon with their cutaneous side effects. PMID- 6240840 TI - [Double-blind group comparison of topical meclocycline, erythromycin and placebo in the treatment of papulo-pustulosa acne]. AB - Ten institutions participated in a controlled clinical trial in order to evaluate the efficacy of topical meclocycline and erythromycin in comparison to placebo with regard to papulopustular acne. Both drugs had been incorporated in the same galenic formulation that served as placebo. The vehicle employed in this study guaranteed equally favorable drug relies for both preparations. At the end of the trial, 419 patients could be evaluated for efficacy. As impartial criterion for evaluation, the number of inflammatory lesions on the right side of the face was counted before and after three months of treatment. In addition, we recorded the patients' and physicians' overall judgment at the end of the study. As compared with placebo, meclocycline as well as erythromycin brought about statistically significant improvement already after two months of treatment. After three months, the results were statistically very highly significant (p less than 0.001). At any time of the study, there could not be demonstrated any difference between the two groups treated with meclocycline and erythromycin. PMID- 6240841 TI - [New technic for guidable balloon dilatation of coronary vessel stenoses]. AB - A new technique for steerable balloon dilatation is described. In contrast to the usual procedure the stenosis is first crossed by a long wire only. To minimize injuries to the vessel wall the wire is equipped with a thickened ball-shaped tip. After the stenosis has been crossed and the wire tip sufficiently advanced the balloon catheter is inserted over the long wire. If necessary the balloon catheter can be removed and another inserted without repeat crossing. If an occlusion is caused by the process of dilatation a perfusion catheter can be advanced distal to the occlusion. Perfusion can be performed with the aid of a simple syringe-tap system because the cross sectional area of this catheter is much larger than a single lumen of the double-lumen balloon catheter. This procedure even allows the dilatation of branching stenoses through the same guiding catheter whereas for the usually performed "kissing balloon" technique two guiding catheters are required. Preliminary experience with 80 patients has shown that crossing of stenoses is facilitated by the new technique because steering of the guide wire and display by contrast medium injections are unhindered. If required the balloon catheter can be changed for another one without difficulty. In the case of an occlusion the lesion can be crossed again without any risk and repeat dilatation or coronary perfusion can be performed. PMID- 6240842 TI - [Occurrence and predictability of progression of high grade coronary vessel stenoses to occlusions]. AB - The aim of this study is to evaluate the incidence and time of occlusions of high grade coronary stenoses and to discover risk factors for the prediction of impending occlusions. At the time of scheduled angioplasty, on average within 4.5 months of the first diagnostic angiogram, 35 (6.5% of 650) vessels were already occluded. Another 5 patients had died on the waiting list and 2 had suffered a non-fatal infarction. In comparison to patients without progression of stenoses of a similar location and severity, special risk for the occurrence of occlusions was found in cases with collaterals, after infarctions (history, ECG, angiogram), and with multivessel disease. The prevalence of atherogenic risk factors was also higher. There are no clear differences between both groups as far as age, sex, nature and duration of symptoms, angiographic morphology of stenoses and waiting time for angioplasty are concerned. The stenotic vessels of the 7 patients who died or suffered infarctions had no collaterals. Thus coronary angioplasty should be performed immediately after the diagnostic angiogram. This leads to an increase in the success rate in patients with impending coronary occlusion. The spontaneous risk, however, of these patients in suffering sudden cardiac death or non-fatal infarction is low. On the other hand acute infarction and sudden death in the group of patients without detectable signs of impending occlusions can only be prevented by shortening the waiting time for angioplasty. PMID- 6240843 TI - [New noninvasive procedures for evaluation of heart and vascular diseases]. PMID- 6240844 TI - [A system for the prevention and organization of the control of pyoderma, mycoses and occupational dermatoses in miners of the Don basin]. PMID- 6240845 TI - [Current problems in the selection of dermatological patients for sanatorium health resort treatment]. PMID- 6240846 TI - [Haxthausen's syndrome (climacteric keratosis palmaris et plantaris)]. PMID- 6240847 TI - [Side effect of dimexide]. PMID- 6240848 TI - Cystic ovaries in a pre-term newborn infant. AB - Oestrogen-producing ovarian cysts in a very pre-term infant led to swelling of the labia majora and of the lower abdominal wall. Following surgical removal of the left ovary the serum concentration of oestradiol decreased temporarily. Less than 2 weeks after surgery several new cysts appeared in the right ovary. Treatment with medroxyprogesterone acetate resulted in disappearance of these cysts. Simultaneously the serum concentration of oestradiol fell to a normal level. PMID- 6240849 TI - Where should spina bifida children go to school? AB - Children with spina bifida who attend ordinary schools are usually found to be less severely handicapped than their PH school counterparts. This study looked at thirty-eight pairs of children born since the introduction of selective surgery and matched for chronological age, one attending an ordinary school and the other PH schools. There was no difference between the two groups for IQ, reading ability or visual motor skills, although PH school children were significantly poorer on number work. Ordinary school children were less likely to need aids for locomotion, to have valves, and to be incontinent, although, as a group, they had a lower self-concept. Results of an analysis on the main discriminating factors indicated that all but two of the PH school children exhibit similar characteristics as those successfully attending ordinary schools. This suggests that the majority of post-selection spina bifida children could be integrated into ordinary schools. PMID- 6240850 TI - The employment of adults with spina bifida. AB - Information on employment was obtained from 157 adults with spina bifida aged 18 26 years. Ninety were given an additional interview, 43% had been employed at some time, but only 19% currently. They mainly did routine, non-manual work for average working hours, but below average pay. They enjoyed their jobs, principally for the social contact, and were well accepted by employees and work mates. Unfortunately, job retention was poor. The 81% who were unemployed largely hoped to find a job, but suitable ones were not available. They considered that they should have more help to find jobs. Their days were mainly spent at home or at day centres. They had no doubts that being unemployed had many disadvantages, of which the principal one was lack of social contact, but financial hardship was also mentioned. PMID- 6240851 TI - Psycho-social achievement in the latency-aged child with spina bifida within the family structure. AB - This project aims: 1) to appraise the psycho-social development of a sample of latency-aged spina bifida children upon entry to school; 2) to learn about the social influences that promote or impede the child's development, and 3) to identify ways that psycho-social intervention can be useful to families in which there is a congenitally disabled child. A longitudinal, observational case study was conducted over a six month period. This approach provided information on the impact of social influences, disability, and trauma on the child's development. The results indicate that a delay in reaching the important physical milestones of independent locomotion and continence hinders the achievement of standard psycho-social developmental goals; it does not exclude their achievement. By the sixth month in first grade, all of the children had adapted satisfactorily to school. Thus, the difference between the able-bodied and the spina bifida child was not one of kind, but one of degree. Spina bifida was found to put no ceiling on the child's psycho-social development. PMID- 6240852 TI - [Diagnostic procedure in osteoporosis]. AB - Osteoporosis is a very important differential diagnosis in chronic back pain. Early diagnosis of osteoporosis remains difficult, as an initial loss of skeletal mass cannot be recognized in X-ray pictures. A clear assessment can only be reached by the application of different non-invasive quantitative methods of bone mineral determination. So far as possible bone mineral content should be measured at an axial and a peripheral site of the skeleton. Crush fractures of vertebrae indicate an advanced calcipenic osteopathy. During the diagnostic procedure of osteoporosis other metabolic osteopathies (e.g. the different forms of hyperparathyroidism and osteomalacia) must be excluded by laboratory examinations or sometimes even by bone histology. If other generalised osteopathies can be excluded one has to look for etiological factors of a possible form of secondary osteoporosis because some of these allow a specific therapeutic approach. In about 80% no disturbances of calciumphosphorous metabolism can be detected, which means that a diagnosis of primary (idiopathic) osteoporosis must be made. In primary and secondary forms of osteoporosis the actual skeletal status and the activity of the osteoporotic process should be defined before beginning a differentiated treatment. PMID- 6240854 TI - [Levels of sodium, potassium, chloride, inorganic phosphate, calcium, glucose, uric acid, urea N and creatinine in the saliva of healthy children with low and high caries activity]. PMID- 6240853 TI - [Amino acids in saliva]. PMID- 6240855 TI - [Incidence of yeasts in the oral cavity in reference to signs of inflammation, the wearing of a removable denture and oral hygiene]. PMID- 6240856 TI - [Effect of antimycotic therapy of denture stomatitis on the bacterial flora of the oral cavity]. PMID- 6240857 TI - [Extreme dystopia of canines or premolars in the mandible caused by intraosseous migration]. PMID- 6240858 TI - [Scintigraphic control study after endosseous implantation of sintered bio vitroceramic]. PMID- 6240859 TI - [Effect of water content on the marginal stability of composites. 2]. PMID- 6240860 TI - [Scanning electron microscopic study of the in vivo solubility of the smear layer]. PMID- 6240861 TI - [Overall surface area of occlusal contacts in static occlusion in dental models]. PMID- 6240862 TI - [Treatment and prognosis of crowding in cheilognathopalatoschisis with special reference to the Vienna concept]. PMID- 6240863 TI - [Juvenile periodontitis]. PMID- 6240864 TI - [Experimental animal studies on the effect of the size and position of the tongue on mandibular growth]. PMID- 6240865 TI - [Inhibitor hemophilia in oral surgery]. PMID- 6240866 TI - [Histochemical-morphometric studies of skeletal muscles in advanced arterial circulation disorders of the extremities]. AB - Biopsies of M. gastrocnemius and Nervus suralis of 12 patients with advanced disturbances of circulation were examined by means of morphometrical and histochemical methods. The histological picture of a neurogenic atrophy of the muscle fibres with partially strong hypertrophy of the slow-twitch fibres was found. The main reaction patterns and the pathogenetic mechanisms are discussed. Alterations in the ratio of type I and type II fibres are described. Fiber type disproportions, i.e. more than 75% type I fibres, may suggest that in hypoxia the type II fibres are more intensely damaged than type I fibres. There are correlations between pathological fibre distribution and the success of vasosurgical treatment. PMID- 6240868 TI - [Substrate property of organic substances in the treatment of drinking water]. AB - A method for the determination of the bacterial growth rate as parameter for the biodegradability of organics in water is described. The increase of the number of bacteria during incubation is measured by turbidity (12 degrees forward scattering) and total cell number counted in the microscope. The method allows to define the influence of water treatment steps (ozone, activated carbon filtration) on the growth rate being a decisive criterion on regrowth problems in distribution systems. PMID- 6240867 TI - [Behavior of submerged skin for the replacement of the anterior abdominal wall in the rat]. AB - 28 albino rats underwent resection of the anterior abdominal wall which was replaced by burried autogenous cutis. Within 8 weeks a firm fibrous plate developed which prevented cicatricial herniation. PMID- 6240869 TI - [In vitro fertilization program in therapy of the sterile marriage. International status and personal experiences]. AB - A review is given about in vitro fertilization (IVF/ET) and embryo transfer in the treatment of sterile couples. Programmes of in vitro fertilization of successful international groups are analysed and discussed, especially the improvements of the method. These international reports were the basis of the programme of in vitro fertilization at women's hospital of the Wilhelm Pieck University at Rostock. The organization of the programme depends on local conditions. Treatment is performed in some so-called IVF-series. The results of the first and second series with 52 patients are reported. The only pregnancy during the second series was an ectopic pregnancy. PMID- 6240870 TI - [Pregnancies caused by in vitro fertilization in cycles, stimulated with human hypophyseal gonadotropin and chorionic gonadotropin]. AB - In a program of in vitro fertilization, laparoscopies for oocyte aspiration were performed on 35 patients receiving human pituitary gonadotropin (hPG) and human chorionic gonadotropin (hCG). Of the 122 preovulatory oocytes which were recovered from these patients, 44 (36%) were fertilized and cleaved, and were transferred. 144 immature oocytes were collected, and attempts were made to mature these in vitro. 40 oocytes (28%) could be fertilized and cleaved, and were transferred. Eight pregnancies resulted from 32 embryo transfers (25%), and 22,9% from laparoscopies, respectively. Of the eight pregnancies, there were three preclinical abortions and two clinical abortions, and three patients are well along in the pregnancy. Among the three patients there is one twin pregnancy. PMID- 6240872 TI - [A transportation vehicle for laparoscopically obtained follicular specimens]. AB - Structure, function and first results with a vehicle for transportation were described. This apparatus allows to store laparoscopic harvested follicular fluids for a while in constant temperature and in air condition with 5% CO2 in compressed air. Simultaneously the follicular fluids were transported in this vehicle from operating theatre to the laboratory. PMID- 6240871 TI - [In vitro fertilization and embryo transfer. Personal experiences in the introduction of laboratory methodology]. AB - Our laboratory technique includes recovery and handling with gametes outside the body, in vitro fertilization, culture of embryos, and finally embryo-transfer. Time-table, culture media and technique of the cultivation as well as laboratory devices are described and than compared with informations about methods from other teams. The necessity of transport of the follicle fluids from operating theatre to laboratory is given caused by local conditions. All dates about number of oocytes (73), quantities of preovulatory oocytes (47) and cleavage rates (55%) are descended from 30 laparoscopic oocyte recoveries of the 2. in vitro fertilization program of the university woman hospital in Rostock, January and February 1984. PMID- 6240873 TI - [Focal nature of tularemia along the course of the Irtysh-Karaganda Canal]. AB - The results of the epizootological survey of the track of the Irtysh-Karaganda canal for tularemia for the period of 1971-1982 are presented. Out of 928 fecal samples from mouse-hunting birds, 16 contained the specific antigen. From Arctic shrews a strain of Francisella tularensis was isolated. PMID- 6240874 TI - [Determination of groups at risk for acute intestinal infections by a population questionnaire]. AB - Questionnaires were distributed in 3308 families divided into two groups: group 1 with no cases of acute intestinal infections and group 2 where such cases were registered. Information contained in the questionnaires was processes by means of computers bzsm-6. The analysis of the data on the occurrence of characteristics indicating the quality of water supply and water consumption (25 characteristics), sewage and sanitation (12 characteristics), living conditions (19 characteristics) showed that the living conditions of the families in group 2 were worse than those of the families in group 1. The occurrence of these characteristics in the families of patients with acute intestinal infections and in the families of carriers were mostly the same, and the existing differences in such characteristics as "fishing", "use of water from ponds for house-hold purposes" proved to be nonessential. The population of the city was divided into four risk groups with regard to the possibility of contacting infection, depending on the conditions of water supply, water consumption and sewage in different housing areas: the group registered as stable on account of sanitary and hygienic conditions, the groups of usual, increased and maximum risk. PMID- 6240875 TI - [Immunoepidemiological characteristics of the duration of a meningococcal carrier state]. AB - The duration of meningococcal carriership in children and adults in the foci of infection and outside such foci and the immunological characteristics relating to group-specific meningococcal antigens A, C, X, Y and Z at different periods after the detection of the infective agent in the nasopharynx have been studied. Carrier state has been shown to last, on the average, 11 days. The duration of the release of meningococci from the nasopharynx has proved to be influenced by the epidemic situation in a given group. Differences in the time course of the immunological reorganization of the body in response to antigenic challenge in prolonged and short-term carrier state have been detected. These data suggest that rapid immune response to meningococcal antigens in the process of short-term carrier state is probably one of the factors preventing the prolonged colonization of the nasopharynx by the infective agent. PMID- 6240876 TI - [Antigenic anachronism of influenza viruses A(H2N2) in Leningrad in 1980. II. The laboratory characteristics of influenza A/Leningrad/80 viruses]. AB - As indicated by the results of the hemagglutination inhibition (HAI) test, influenza viruses A/Leningrad/80 contain hemagglutinin (HA), similar to that of virus A/Singapore/1/57 (H2N2). Neuraminidase contained in viruses A/Leningrad/80 belongs to serological subtype N2 and is similar to that of virus A/Singapore/1/57 (H2N2). No differences in the polypeptide composition of the virus-induced proteins of viruses A/Leningrad/527/80, A/Leningrad/549/80, A/Leningrad/553/80 and virus A/Singapore/1/57 used as reference have been detected in the study of their electrophoretic mobility in polyacrylamide gel, as well as the mobility of duplexes obtained by the hybridization of the virion and complement RNA of viruses A/Leningrad/553/80 and A/Singapore/1/57. The results of the HAI test with antisera to purified HA indicate that virus A/Leningrad/549/80 contains HA similar to that of viruses A(H2N2) isolated in 1957, but not in 1964. The HAI test with the sera of polecats having the infection permits the differentiation of viruses A/Leningrad/80 from epidemic viruses A(H2N2) isolated in 1957-1965, including reference virus A/Singapore/1/57. In relation to the latter, the isolates of 1980 are older antigenic mutants. The isolates of 1980 are distinguished from virus A(H2N2), isolated in 1975 from the system of persisting influenza infection in a tissue culture, by mutation in NS-gene and the properties of RNA-polymerase. The authenticity of the isolation of viruses A(H2N2) in Leningrad in 1980 has been proved. PMID- 6240877 TI - [Incidence of infectious diseases in children in the 1st 7 years of life]. AB - The dynamics of changes in the occurrence of infectious diseases in 1180 children during the first 7 years of life has been studied. The possibility of dividing children into groups with rare and frequent occurrence of diseases as early as during the first years of life has been demonstrated. The group of children falling ill frequently determines, to a considerable extent, the morbidity level in infectious diseases among children of the corresponding age group. PMID- 6240878 TI - [Pathogenesis of experimental thyrotoxic myopathy]. AB - The data obtained in mice with experimental thyrotoxic myopathy included a decrease in the median diameter of the muscle fibers by 17.1 per cent and various focal degenerative changes in less than 20 per cent of the muscle fibers; a statistically significant elevation in the activity of alpha-glycerophosphate dehydrogenase, as well as a reduction in phosphorylase activity and glycogen levels. There was also a significant diminution in the median diameter of the motor terminal plates, a decrease in cholinesterase activity and intensified collateral ramification of the distal axons. The major cause of the muscular weakness and structural changes in the skeletal muscles in thyrotoxic myopathy seems to lie in lowered cAMP concentrations and a weakened cAMP-dependent regulation of protein kinase. PMID- 6240879 TI - Effect of progestogen (Depo-Provera) on annulate lamellae in endometrial carcinoma. AB - The authors studied electron microscopically the effect of a large dose of medroxyprogesterone acetate (Depo-Provera) on the fine structure of endometrial carcinoma, with special regard to the annulate lamellae of the cells. Following treatment in one-third of their cases of highly-differentiated endometrial carcinoma the glandular epithelial cells were found to show a marked regression. After using a large dose of progestogen, the oestrogen-dependent annulate lamellae 'disappeared' from the cytoplasm of the cells. This phenomenon may be one of the morphological manifestations of subcellular oestrogen-progesterone antagonism. PMID- 6240881 TI - [Malignant tumors of extrahepatic bile ducts]. AB - In connection with increased incidence of extrahepatic bile duct cancer, clinicalpathological characteristics, treatment and prognosis of this particular tumor are revised on the basis of data obtained from patients series observed by the authors and from those of the reference. PMID- 6240880 TI - Hysteroscopic evaluation of intrauterine progesterone contraceptive system as a treatment for abnormal uterine bleeding. AB - Intrauterine Progesterone Contraceptive System has been used in twenty patients aged 45 to 52, affected by dysfunctional uterine bleeding due to glandular hyperplasia (6 cases), focal glandular hyperplasia (8 cases), cystic hyperplasia (4 cases) and adenomatous hyperplasia (2 cases). Hysteroscopy and endometrial biopsy were performed every two months after insertion of IPCS. Complete regression or clear improvement were observed in all cases. The question if regression may be considered permanent or temporary remains to be answered. PMID- 6240882 TI - Changes in skin blood flow and temperature during spinal analgesia evaluated by laser Doppler flowmetry and infrared thermography. AB - Changes in skin blood flow and skin temperature during spinal analgesia and "sham" spinal analgesia were studied using laser Doppler flowmetry and skin temperature measurements on patients scheduled for transurethral resection. Infrared thermography was also used. During "sham" spinal analgesia skin blood flow decreased 17.7% +/- 37% (s.d.) and skin temperature fell 0.05 degrees C +/- 0.6 (s.d.) degree C. The height of the blockade was T10 or above in all cases. Using the laser Doppler technique with measuring points from the clavicle to T12, a tendency towards increased skin blood flow was seen in six cases out of 20 at T10 (significant elevations in 3/20) and in 14 cases out of 20 at T12 (significant elevations in 7/20). Skin temperature measurements and thermography showed a tendency towards cooling in the thoraco-abdominal region in the vast majority of the cases and a marked temperature elevation in the foot only. No differences between hyperbaric and glucose-free solutions for spinal analgesia were noticed. The conclusion of this study is that during spinal analgesia the extent of sympathetic blockade is less than the extent of analgesia. PMID- 6240883 TI - Muscle fiber type differentiation and satellite cell populations in normally grown and neonatally denervated muscles in the rat. AB - To examine the neural influence upon fiber type differentiation in developing muscles, newborn rats were subjected to sciatic nerve dissection, and the denervated extensor digitorum longus (EDL) (white) and soleus (red) muscles were examined in chronologic sequence by means of histochemistry and electron microscopy. The skeletal muscles in the newborn rats were undifferentiated (type 2C fibers seen on ATPase staining) and contained numerous myotubes. In the controls, the type 2C fibers started to differentiate at around 5 days and had almost completed type differentiation by 30 days in EDL and by 90 days in soleus muscles. On the other hand, none of the fibers in the neonatally denervated muscles developed into well differentiated type 1 and 2 A fibers, but both the EDL and soleus showed long-lasting type 2C and 2B populations. The satellite cells in the denervated EDL and soleus muscles decreased in number at the same rate as in the control muscles with maturation. The absence of a neural supply in the developing muscles induced a delay in muscle fiber type differentiation but did not influence the satellite cell populations in either EDL or soleus muscles. PMID- 6240884 TI - Visually evoked potential (VEP) acuity: testability in a clinical pediatric population. AB - The visually evoked potential (VEP) elicited by pattern response is used to assess the visual acuity of preverbal infants in research situations, but few reports indicate the percentage of patients successfully completing the tests (testability). Data are presented to illustrate the testability of acuity assessed by VEPs with clinical populations of preverbal and neurologically handicapped children. 166 referrals in a 9-month period to an electrodiagnostic clinic indicated that 75% of the referrals less than 3 years old, and 87% of the neurologically handicapped referrals were testable. The testability of VEP acuity is as great or greater than other procedures for examining the visual functions of non-verbal or unco-operative patients. PMID- 6240886 TI - Radionuclide scintimetry for diagnosis of complications following femoral neck fracture. AB - A scintimetric study using Tc-99m MDP was made of 54 patients with delayed union, nonunion, or late segmental collapse of the femoral head, 4-92 months after femoral neck fracture. In radiographically verified collapse, the radionuclide uptake ratio between the femoral head on the fractured and on the intact side (HHR) was significantly higher than in fractures resulting in delayed union or nonunion. On the basis of scintimetric and radiographic findings, the patients with healing disturbances could be divided into three groups, characterized by the following features: Satisfactory post-reduction position of the fracture without subsequent redisplacement and a high HHR, which as a rule turned out to be delayed union; The same radiographic pattern but with a lower HHR, which in most cases resulted in nonunion; Inadequate reduction or early redisplacement of the fracture with a high HHR, which resulted in nonunion. The fractional precision in discriminating between different types of disturbed fracture healing by means of skeletal scintimetry was 0.86 in this study. This non-invasive and technically simple method would therefore be a valuable complement to radiography in the assessment of healing, more than 4 months after fracture of the femoral neck. PMID- 6240885 TI - Ectopic bone after hip replacement. Excision and free fat transplants in four cases. AB - In four patients ectopic bone formed after total hip replacement was replaced with free fat transplants. One year later the patients were free from pain, and hip flexion had increased by 60 degrees on average. Ectopic bone was completely absent in one patient, and markedly reduced in the remaining three patients. Bone scintigraphy was found to be a sensitive technique to reveal early ectopic bone formation. Fat transplantation seems to be a satisfactory complement in the treatment of ectopic bone. PMID- 6240887 TI - Comparison of skeletal and bone marrow radionuclide scintimetry of femoral neck fracture. AB - Twenty-six patients with late complications following femoral neck fracture were examined with both skeletal and bone marrow radionuclide scintimetry. There was no correlation between the methods with respect to the quantitative assessment of femoral head vascularity based on different uptake ratios comparing the fractured and the intact side. Skeletal scintimetry always had good image quality and permitted reliable differentiation between nonunion of the fracture and late segmental collapse, in contrast to bone marrow scintimetry which gave poor image quality. Skeletal scintimetry thus seems superior to bone marrow scintimetry for assessment and differential diagnosis of late complications following femoral neck fracture. It is emphasized that the physiological mechanisms for radionuclide uptake must be taken into account when comparing scintimetric studies using different tracers. PMID- 6240888 TI - The laser Doppler: a non-invasive measure of cochlear blood flow. AB - The present investigation demonstrates the utility of the laser Doppler flowmeter to provide a measure of cochlear blood flow dynamics. Cochlear and cutaneous blood flow were compared with arterial blood pressure during and following exposure to Angiotensin II, 5% carbon monoxide, 100% oxygen, mannitol, and saline. The observations indicate that: 1) cochlear blood flow generally parallels cutaneous blood flow; however, 2) when cutaneous beds vasoconstrict (e.g., AII, alpha-agonists), cochlear blood flow parallels blood pressure; and, 3) under the influence of agents that affect peripheral and central circulation (5% CO, 100% O2), cochlear blood flow may dissociate from cutaneous blood flow and blood pressure. The implications of these findings are discussed in terms of local control mechanisms that may be involved in the inner ear vasculature. PMID- 6240889 TI - Longitudinal study of calcium metabolism in male puberty. II. Relationship between mineralization and serum testosterone. AB - Height velocity, bone mineral content (BMC), serum concentrations of alkaline phosphatase (AP), testosterone, dehydroepiandrosterone (DHEA) and androstenedione (A-dione) were determined as a part of a longitudinal study of calcium metabolism in normal male puberty. The time of maximal increase (Tm) in concentrations was calculated for 20 boys from a curve-fitting analysis program. Highly significant correlations were found between Tm testosterone and Tm BMC (r = 0.73, p less than 0.001); Tm AP and Tm BMC (r = 0.68, p less than 0.001). The mean difference in time between Tm testosterone and Tm BMC was 4.7 months and between Tm AP and Tm testosterone 0.7 month. Our data indicate a very close relationship between testosterone, osteoblastic activity, and mineralization in normal male puberty, whereas the adrenal androgens do not seem to have a major influence on the mineralization at the male puberty growth spurt phase. PMID- 6240890 TI - Premature thelarche--natural history and sex hormone secretion in 68 girls. AB - Data obtained during long-term follow-up of 68 girls with premature thelarche were analysed. In 85% onset was before the age of 2 years, in 30.8% being present at birth. In 44.1% there was a regression after 3 2/12 +/- 2 8/12 years (SD). Basal levels of plasma FSH and response to LH-RH were significantly higher than prepubertal controls (1.93 +/- 1.56 vs. 0.8 +/- 0.1 mU/ml and peaks 12.3 +/- 5.4 vs. 7.9 +/- 1.0 mU/ml respectively; p less than 0.001). Twenty-seven of 52 patients tested had increased plasma estradiol and in 27 of 40 patients tested, urocytograms or vaginal smear showed estrogenization. Basal levels of LH and response to LH-RH were prepubertal. The girls with premature thelarche were significantly taller than normal controls of the same age (p less than 0.001). These results suggest that premature thelarche is an incomplete form of precocious sexual development probably due to derangement in the maturation of the hypothalamo-pituitary-gonadal axis which results in a higher than normal secretion of FSH, as well as a defect in the peripheral sensitivity to the sex hormones. PMID- 6240891 TI - Neonatal cerebral blood flow velocity I. An in vitro validation of the pulsed Doppler technique. AB - A combined pulsed and continuous Doppler instrument was used to assess flow velocities in an in vitro model designed to simulate small deeply lying arterial vessels. Diameters of the model vessels, depth under the transducers and the pulsatile flow patterns were chosen to simulate the corresponding conditions that can be expected when cerebral blood flow velocities are measured with this technique through the anterior fontanel in newborn infants. Computer analysis of the space average velocity signal from the pulsed Doppler mode, showed that the area under this curve, which corresponds to distance, was closely correlated to true flow over a wide range of flows in vessels of different diameters. This variable is suggested to be the closest estimate of true flow, when the diameter of the vessel under study cannot be accurately measured. PMID- 6240892 TI - Nine-year follow-up of infants weighing 1 500 g or less at birth. AB - A nine-year follow-up of 116 children born consecutively in 1971-74 with a birthweight of 1 500 g or less showed that 59 had died. Of those who were alive, four had severe motor and/or mental handicaps and three were blind because of retrolental fibroplasia. The low birthweight children without severe handicaps were found to have impaired motor function, speech defects and impaired school achievement more often than the controls. There was a significant correlation between the test results at the age of five and nine years, which indicates that children with school failure can be recognized and early remedial treatment started before school or on starting school. PMID- 6240893 TI - [Two new formulae for evaluating effectiveness of drug combinations and revision of Burgi's and Jin's modified Burgi's formula]. PMID- 6240895 TI - Modification of effects of repetitive restraint stress on brain biogenic amines by L-tyrosine. PMID- 6240896 TI - [Effects of injection of morphine into the head of the caudate nucleus on activities of neurons of the nucleus raphe magnus in rats]. PMID- 6240899 TI - [Anti-arrhythmic action of total flavones of Choerospondias axillaris fructus]. PMID- 6240900 TI - [Effects of oral diltiazem on left ventricular function in patients with coronary disease]. PMID- 6240901 TI - [Effects of tetrandrine on seven vascular smooth muscles]. PMID- 6240902 TI - [Effect of diethyllipoamide on DNA damage and repair of gamma-irradiated mouse bone marrow cells]. PMID- 6240904 TI - [Effect of potassium deficiency on magnesium metabolism of rats]. PMID- 6240903 TI - [Effect of gossypol acetic acid on the induction of sister chromatid exchange of spermatogonial cell in mice]. PMID- 6240905 TI - [Metabolic changes in phospholipids in animals fed with low selenium]. PMID- 6240907 TI - [Resin hemoperfusion for acute pentobarbital poisoning in rats and rabbits]. PMID- 6240908 TI - [Body retention of 169Yb-citrate and its excretion by 4 chelating agents]. PMID- 6240909 TI - [Penetration of 169Yb-citrate through intact and abraded skins]. PMID- 6240910 TI - Mechanisms of transport and assembly of myelin proteins. AB - The present study was carried out in order to obtain further information regarding the mechanism of transport and assembly of myelin proteins in different subcellular fractions isolated from brain slices incubated in vitro with radioactive amino acids under different experimental conditions. It was found that proteolipid protein (PLP) showed a lag in the entry into the myelin membrane, while basic and Wolfgram proteins appeared to be inserted in this structure immediately after their synthesis. Addition of 500 microM colchicine to the incubation medium blocked the transport of PLP, while the entry of the other proteins was not affected. Pulse-chase experiments using cycloheximide suggest that a precursor-product relationship between microsomes, fraction SN4 and myelin exists only for PLP. The results obtained allow us to draw the following conclusions: The delay in the entry of PLP into myelin membrane is probably due to the time required for its transport towards the final site of assembly; the microtubular network of the oligodendroglial cell is directly involved in the transport of PLP; basic and probably Wolfgram proteins follow a route which clearly differs from that of PLP; delivery of myelin proteins from the site of synthesis towards their site of deposition depends, at least, on two different mechanisms of intracellular transport. PMID- 6240911 TI - Amino acid sequences around the cystine residues in alpaca growth hormone. AB - Half-cystine peptides were isolated from the enzymatic digest of reduced and carbamidomethylated alpaca growth hormone. From their amino acid composition and determination of the end terminal residues we propose the amino acid sequence around the two disulphide bridges, partially based on homology with other mammalian growth hormones. The proposed sequence is identical to that of equine growth hormone and very similar to those of rat, bovine and ovine hormones. PMID- 6240912 TI - Pseudocooperative effects in reactivation of membrane-bound enzymes with phospholipids. AB - The kinetic mechanism for reactivation of membrane-bound enzymes by lipids is analyzed on the basis of multiple equilibriums between the enzyme (which is assumed to contain n identical, non-interacting binding sites) and the lipid. The rate equations derived when only the fully occupied enzyme species ELn (or ELn and the next most highly occupied species ELn-1, ELn-2,..., ELn-i) is catalytically active can fully account for the apparent positive cooperativity observed in the plots of enzyme activity as a function of phospholipid concentration. A general equation for the cases in which more than one lipid species are simultaneously present in the reaction medium is presented which allows to test whether the binding sites are indeed non-interacting, as well as whether the active species have the same catalytic constant (kcat), regardless the nature of the lipid bound to the binding sites. This analysis demonstrates that, in addition to apparent positive cooperativity, more complex curves resembling mixed cooperativity may be obtained with simple systems when interaction between protein subunits (i.e., association-dissociation equilibriums) are present. Finally, some theoretical problems and pitfalls in the interpretation of the experimental results will be discussed. PMID- 6240913 TI - Increased carbon tetrachloride-stimulated chemiluminescence in the in situ liver of barbital-treated mice. AB - Mice treated with barbital (0.1% in the drinking water) during 15 days showed a 63% increased endoplasmic reticulum mass. The carbon tetrachloride-stimulated chemiluminescence of the in situ liver was 51% increased after barbital treatment. Hydroperoxide-stimulated chemiluminescence of liver homogenates and microsomal suspensions were increased by 140 and 92%, respectively, in the barbital-treated mice. Spontaneous liver chemiluminescence (109 cps/cm2) was found unchanged after barbital treatment. Superoxide dismutase, catalase and glutathione peroxidase activities were 109, 61 and 103%, respectively, increased after barbital treatment. The results are consistent with a primary role of cytochrome P 450 in the biotransformation of CCl4, which initiates a radical chain reaction leading to the production of powerful oxidizing species. Apparently, superoxide dismutase, catalase and glutathione peroxidase are synthetized in a coincident manner with respect to cytochrome P 450. PMID- 6240914 TI - Basic and acidic hydrophilic residues involved in the interaction between protomers of the bovine growth hormone dimer. AB - Reactivity of histidine and arginine residues--as well as of carboxyl-groups--in the covalently stabilized dimer of bovine growth hormone, was studied in comparison with their reactivity in the monomeric form. Results obtained by reaction of histidine and arginine residues with ethoxyformic anhydride and cyclohexanedione, respectively, were similar for both proteins. The reactivity of two carboxyl-groups towards a soluble carbodiimide becomes impaired in the dimer, thus suggesting that their location is within the protomer interaction area. PMID- 6240915 TI - Lack of correlation between liver RNA polymerase I and ornithine decarboxylase activities after re-feeding of protein-depleted mice. AB - When mice fed on a protein-depleted diet are restored to the normal diet (re feeding), there is a 2-fold increase in liver RNA polymerase I activity. The results obtained with pactamycin; an inhibitor of protein synthesis, suggest the presence of short-lived proteins which are required for inducing an activated state of transcription. To gain an insight on whether ornithine decarboxylase (ODC)--the first enzyme in polyamine biosynthesis--is the labile protein that regulates rRNA synthesis, we have investigated the correlation between liver ODC and RNA polymerase I activities under different nutritional conditions. We have also studied the effects of alpha-difluormethylornithine (alpha-DFMO)--a specific ODC inactivator--on rRNA transcription. The results indicate that, after re feeding, there is an abrupt increase in ODC activity that rapidly declines, while RNA polymerase I is still increasing. On the other hand, alpha-DFMO--which inhibits the elevated activity of ODC--has not effect on rRNA transcription. PMID- 6240916 TI - Hydrophobic residues involved in the interaction between protomers of the bovine growth hormone dimer. Methionine and tyrosine residues. AB - The bovine growth hormone dimeric form covalently stabilized by cross-linking with dimethyl suberimidate (DMS) and the hormone modified by DMS without forming covalent links with other hormone molecules (DMS-bGH) were oxidized with chloramine-T at molar-ratios of 2 and 50 with respect to methionine content. The extent of oxidation undergone by each methionine residue, estimated on the purified tryptic peptides, closely resembled that obtained for the native hormone, thus suggesting that methionine residues are not involved in the protomers interaction area. Evaluation of the reactivity of tyrosine residues toward tetranitromethane indicated that, in both the covalent dimer and DMS-bGH, tyrosine residues 35, 174 and 142 are the more susceptible to undergo reaction. Net charges can be induced in the iodotyrosine residues in the iodinated hormone, by setting the pH at 10.5. At this pH, dissociation of a fraction of uniformly iodinated hormone was observed in the derivatives containing 2 or more iodine atoms, indicating that tyrosine residues might integrate the contact area between protomers. PMID- 6240917 TI - Breakdown of proteins from mouse liver subcellular fractions. Effect of nutritional changes. AB - The rapid restoration of liver protein mass observed in protein-depleted mice when they are fed with an adequate diet is quantitatively explained by a large decrease in the average rate of breakdown of total liver proteins. This study was performed in order to know whether this inhibition of breakdown affects in the same way all the protein constituents of the tissue, or only affects a group of these proteins belonging to a particular subcellular fraction. Subcellular fractions were obtained by differential centrifugation. The relative rates of breakdown of their proteins were estimated by the conservation of radioactivity in these proteins previously labelled by the administration of NaH14CO3 to mice. The results obtained indicated: 1) a general decrease in the rate of breakdown of proteins of subcellular fractions from re-fed livers compared with livers of protein-depleted mice; 2) a decrease of breakdown of proteins from cytosol in re fed mice which is higher as lower is the molecular weight of the proteins subunits. PMID- 6240918 TI - Characteristics of insulin receptors in a clonal line of rat pituitary tumor cells in culture. AB - The presence of insulin binding sites in a clonal line of cells from rat pituitary tumor (GH1 cells) is described. The binding of insulin was a reversible and specific process. Binding of 125I-insulin to GH1 cells was inhibited by unlabeled insulin and to a minor extent, by proinsulin and desalanine insulin in direct proportion to their biological activities. Trypsin abolished the insulin binding to the cells. Twelve hours incubation of cells with insulin (5 microM) reduced in a 45% of the number of binding sites for the hormone. 125I-insulin bound to GH1 cells dissociated with a t 1/2 of 8 min. At 24 C labeled insulin was degraded by GH1 cells. No degradation was detected at 6 C. Unlabeled insulin inhibited most of the degradation of 125I-insulin, suggesting that degradation resulted from a saturable process. At steady-state, radioactive degradation products as well as 125I-insulin were recovered from GH1 cells. PMID- 6240919 TI - Growth hormone radioimmunoassay using monoclonal antibodies: a useful method to avoid human chorionic somatomammotropin interference in serum samples. AB - The suitability of several monoclonal antibodies for specific radioimmunoassay of serum human growth hormone was tested. Sera from pregnant women with high human chorionic somatomammotropin levels were used. From both theoretical and experimental considerations, some specifications were recommended in order to select appropriate monoclonal antibodies for clinical determinations. PMID- 6240920 TI - Effects of amino acid and serum deprivation on protein synthesis and degradation in cultured Chinese hamster ovary cells. PMID- 6240921 TI - Chronic low-back pain and depression: an epidemiological survey. AB - The author evaluated the presence of depression among 64 male workers at an engineering factory, suffering from chronic low-back pain (19 organic cases and 45 idiopathic cases). Moreover, the frequency of depressive spectrum disorders was assessed among their first degree relatives. No significant differences emerged between organic and idiopathic cases. PMID- 6240922 TI - Plasmapheresis and cold sensitivity of immunoglobulin molecules. II. A study of macroglobulinemia polyclonalis spuria and immune complex disease. AB - The indications for plasmapheresis in the different hyperviscosity syndromes are discussed on the basis of data on relative serum viscosity at 13 and 37 degrees C. Beside monoclonal macroglobulinemia there are conditions with a high content of polyclonal IgM and also of IgG and IgA where hyperviscosity is a dominant symptom. The importance of what may be called macroglobulinemia polyclonalis spuria is stated and a number of patients belonging to this type are discussed. Polyclonal increase in IgG, even at high levels, usually does not cause severe hyperviscosity. Case histories of patients with rheumatoid disease and marked hyperviscosity constitute one group. Another is formed by diseases leading to the development of immune complexes. Such complexes are usually caused by binding of polyclonal IgG to monoclonal IgM, but other combinations are also known. A number of clinical examples of these different disease conditions, some probably indicating intense plasmapheresis, are analyzed. The limited value of plasmapheresis alone without cytostatic treatment is stressed as regards hyperviscosity. Another indication is removal of noxious protein components. PMID- 6240923 TI - Paternal and maternal transmission in Huntington's disease. PMID- 6240924 TI - Gene A protein interacting with recombinant plasmid DNAs containing 25-30 b.p. of the phi X174 replication origin. AB - Synthetic oligodeoxyribonucleotides, DNA ligase and DNA polymerase were used to construct double-stranded DNA fragments homologous to the first 25, 27 or 30 b.p. of the 30 b.p. origin region of bacteriophage phi X174 (nucleotides 4299-4328 of the phi X174 DNA sequence). The double-stranded DNA fragments were cloned into the kanamycin resistance gene of pACYC177 (AmpR, KmR). Transformants were picked up by antibiotic selection and filter-hybridization using one of the oligodeoxyribonucleotides as a probe. Approximate lengths of the inserts were determined by restriction enzyme analysis. Exact length and orientation of each insert was determined by DNA sequencing. Plasmid DNA with an insert homologous to the first 25 b.p. of the phi X174 origin is not nicked by the gene A protein. However, plasmid DNA containing the 27 b.p. fragment in either orientation is nicked by the gene A protein, as well as plasmid DNAs containing the first 28 b.p. or the complete 30 b.p. conserved origin region of the isometric phages. PMID- 6240925 TI - Fidelity of DNA replication in vitro. PMID- 6240926 TI - Replication of phi X174 DNA by calf thymus DNA polymerase-alpha: measurement of error rates at the amber-16 codon. PMID- 6240927 TI - Initiation of DNA synthesis on single-stranded DNA templates in vitro promoted by the bacteriophage lambda O and P replication proteins. AB - The bacteriophage lambda O and P protein replication initiators, in conjunction with six purified Escherichia coli replication proteins, replicate the single stranded chromosomes of phages M13 and phi X174 to a duplex form. Several discrete steps are involved in this DNA synthesis reaction. In an ATP-dependent step that precedes priming, the lambda O and P proteins interact with the Escherichia coli dnaJ and dnaK proteins to transfer the bacterial dnaB protein onto DNA coated with single-stranded DNA binding protein. This creates a stable prepriming intermediate, isolable by gel filtration, that is rapidly primed and replicated upon the addition of primase and DNA polymerase III holoenzyme. Each of the eight proteins required for this nonspecific single strand replication reaction also have physiological roles in the replication of the bacteriophage lambda chromosome in vivo. We propose a scheme for the lambda O and P protein dependent initiation of DNA synthesis that may be relevant to strand initiation events occurring during lambda DNA replication. PMID- 6240929 TI - 5-Hydroxytryptamine releasing activity in culture supernatants of guinea pig lymphocytes. AB - 5-Hydroxytryptamine (5-HT) is not only involved in anaphylactic reactions but also in delayed-type hypersensitivity (DTH) reactions. Supernatants of cultivated guinea pig spleen lymphocytes were investigated for possessing 5-HT releasing activity. Both fractionated supernatants of mixed lymphocytes unspecifically stimulated by Concanavalin A (Con A) and fractionated supernatants of non stimulated mixed lymphocytes decrease the 5-HT content of rabbit thrombocytes. Fractions of a molecular weight smaller than 12,500 daltons are more effective than fractions of a higher molecular weight range. The 5-HT releasing activity of the supernatants is discussed in comparison to a cell migration stimulating activity. PMID- 6240928 TI - Effects of the H2-receptor agonist dimaprit on lymphocyte responsiveness in vitro. AB - The histamine H2-agonist dimaprit was found to increase the response of rat spleen cells to the T-cell mitogen Concanavalin A, when present at concentrations of 10(-5) and 10(-4)M. Higher concentrations of dimaprit were cytotoxic. The enhanced response seemed to be associated with an inhibitory effect of dimaprit on T-suppressor cell activity rather than with a direct mitogen-like stimulation of lymphocyte proliferation or with an interference with monocyte/macrophage functions. The stimulatory effects of dimaprit were not reversed by the H2 receptor antagonist, cimetidine, nor by the beta-receptor antagonists metoprolol and H 35/25. Addition of the H1-receptor antagonist, mepyramine, further increased the stimulatory effect of dimaprit on lymphocyte responsiveness. PMID- 6240930 TI - Comparative effects of long term treatment with etodolac, naproxen and ibuprofen on articular and bone changes associated with adjuvant arthritis in rats. AB - The effect of prolonged treatment with etodolac (8 mg/kg) on the articular and bone pathology at the tibiotarsal joint associated with adjuvant arthritis in the rat has been studied and compared to the effects produced by treatment with naproxen (8 mg/kg) and ibuprofen (50 mg/kg). Drug effects were assessed by radiologic and histopathologic examinations. The effects on hindpaw edema, hindleg function, and body weight gain were also evaluated. Treatment was initiated on day 16 after adjuvant injection and continued for 28, 56 or 84 days. The degree of relapse which occurred after a 28 day period without treatment following 28 or 56 days of treatment was also assessed. Etodolac prevented the progression of the disease. Further, it appeared to diminish the incidence and severity of the lesions already present on day 16 before drug treatment began. All the parameters measured were improved and there was good agreement between the radiologic and histopathologic assessments of joint damage. At the doses used, the onset of drug activity was more rapid with etodolac than with either of the other two drugs. By comparison naproxen and ibuprofen inhibited the progression of joint damage, but neither drug consistently decreased the magnitude of the joint damage below that of day 16. With all three drugs there was less resurgence of disease symptoms when treatment was stopped after 56 days rather than 28 days of drug administration. PMID- 6240932 TI - Alveolar lymphocytes in the follow-up of sarcoidosis. AB - Bronchoalveolar lavage (BAL) was performed in a group of 25 patients with pulmonary sarcoidosis in order to monitor variations in alveolar lymphocytes (AL) in comparison to the clinical evolution of the disease. Two BAL were performed in each patient, the second 6-12 months after the first (8.9 +/- 3, M +/- SD). Twelve patients were classified as improved and 13 as unimproved on the basis of a score of changes in the clinical picture, x-ray, respiratory function, immunological and biochemical tests. There was a significant decrease (p less than 0.001) of the percentage of AL in 66% of cases in the improved group, but not in the unimproved group, where, on the contrary, it was possible to observe an increase in the percentage of AL in 46% of these cases (n.s.). In 9 of 11 patients followed for 1-5 years with at least 3 BAL, AL behaviour correlated with clinical evolution. On the basis of the parameters studied, it was possible to show a correlation between lymphocytes, alveolitis and clinical evolution, especially in patients with an improved course. While a single BAL does not seem to be sufficient to show the course of the disease, repeated long-term washings allow a more accurate staging of sarcoidosis and can give early warning of relapses even when the conventional parameters (clinical, radiological and functional) are unchanged. Our aim was to look for a simpler parameter, which could be used routinely by even unspecialized laboratories, who are not able to type lymphocytes. PMID- 6240931 TI - Differential effects of pharmacologic agents on the reverse passive Arthus reaction in guinea pigs. AB - Five different pharmacologic agents were examined for their effects upon edema, hemorrhage, and vascular infiltration by neutrophils in the reverse passive Arthus reaction (RPAR) in guinea pigs. Two agents, colchicine (3.0 mg/kg p.o.) and ibuprofen (100 mg/kg p.o.) significantly inhibited all three parameters of RPAR. Cobra venom factor (100 units/kg i.p.) inhibited edema and hemorrhage but it did not inhibit neutrophil infiltration. Aminophylline and sulfinpyrazone (100 mg/kg p.o.) inhibited only hemorrhage; they did not inhibit edema or neutrophil infiltration. The results from these studies with five chemically or biologically unrelated pharmacologic agents suggest that the RPAR in guinea pigs can be separated into its basic components (edema, hemorrhage, and neutrophilic infiltration) by selective inhibitors. Inhibition of edema and hemorrhage, or hemorrhage alone of the two-hour RPAR in guinea pigs is not dependent upon inhibition of neutrophilic infiltration. PMID- 6240933 TI - [Age-dependence of adenosine deaminase activity in mouse lymphocytes from the spleen and thymus]. AB - The ADA activity was determined in splenocytes and thymocytes of female CBA-mice in dependence on the age of the animals. The investigations were carried out in period of 0 to 120 weeks, the enzyme activities of corresponding cells of animals in the age of 6 weeks served as controls. Whereas the ADA activity of splenocytes did not change during the time of investigations (P = 5%; not significant in analysis of variance), the enzyme activity of thymocytes was diminished significantly in all animals older than 14 weeks. The ratio of the ADA-activities in splenocytes and thymocytes was 1:2 at the beginning of the investigations and 1:1 after 120 weeks. PMID- 6240934 TI - [Effect of carrageenan, galactose and 2,4-dinitrophenol on leukocyte phagocytosis of Staphylococcus aureus and E. coli]. AB - The influence of carrageenan (0.1, 0.05 and 0.01%), galactose (1 X 10(-1), 1 X 10(-2) and 5 X 10(-2) mol/l) and 2,4-dinitrophenol (5 X 10(-4), 1 X 10(-4), 5 X 10(-5) and 1 X 10(-5) mol/l) on the phagocytosis of Staphylococcus aureus SG 511 and E. coli 04/K31 by polymorphonuclear neutrophil granulocytes was studied. At the same time the capacity of the germs to grow and multiply in presence of different concentrations of the analysed compounds was tested. The phagocytosis of Staphylococcus aureus SG 511 was not inhibited by carrageenan, galactose and 2,4-dinitrophenol, but an influence on the phagocytosis of E. coli 04/K31 could be clearly demonstrated (0.1 and 0.05% carrageenan, 1 X 10(-1) mol/l galactose, 5 X 10(-4) and 1 X 10(-4) mol/l 2,4-dinitrophenol). The multiplication of Staphylococci and E. coli was not influenced by all three compounds. PMID- 6240935 TI - Anti-dsDNA antibodies in sera of patients without systemic lupus erythematosus. AB - 133 sera of patients without systemic lupus erythematosus (SLE) have been analyzed by an ultramicro ELISA for antibodies to dsDNA. 14 sera (10.5%) had antibody concentrations greater than 120 mU/ml ("positive"). Additionally, 29 sera (21.5%) had antibodies within the range 60 . . . 120 mU/ml ("borderline"). Pathogenetic significance is discussed briefly. PMID- 6240936 TI - Further studies on the application of the micromethod of phagocytosis using cadmium microcrystals as phagocytosis particles. AB - The use of Cd microcrystals together with a monolayer technique using small quantities of whole blood offers several advantages for routine studies of phagocytosis. The original method by Miler was especially minimized with regard to the necessary quantity of serum. Homologous serum was replaced by heterologous guinea-pig serum and the method was simplified by the omission of opsonization. A comparison of the stimulatory effect of inactivated and native serum as well as the inhibition of phagocytosis by trypan blue allows us to characterize Cd phagocytosis as complement-dependent. PMID- 6240937 TI - [A further confirmation of the high idiotypic specificity of carp anti-human myeloma protein sera]. AB - Previous investigations about the specificity of carp anti-idiotypic sera could be confirmed by comparison with corresponding antisera of guinea pigs. 3 carp antihuman myeloma-protein sera rendered as idiotypic specific after an appropriate absorption were tested in the passive hemagglutination inhibition test. They showed no difference to the parallel tested guinea pig antisera. It can be assumed that between fish antibodies and antibodies of mammals no functional difference exists in respect of antigen binding. On the other hand mammals exhibit a higher extent of structural antibody heterogeneity. PMID- 6240938 TI - [Characterization of a series of monoclonal antibodies against human T cells]. AB - A set of 6 monoclonal antibodies is characterized reacting only with human T cells but not with B lymphocytes. The antibody BL-T1 binds to the E receptor, being there on all mature T cells and on the majority of thymocytes. All respectively the majority of peripheral T cells but only subpopulations of thymocytes are recognized by the monoclonals BL-T2, BL-T3, BL-T4 and BL-T5. For identification and quantification of mature human T cells especially the antibody BL-T2 is suitable. The antigen recognized by BL-E1 is missing on peripheral B lymphocytes but expressed not only on T cells but also on erythrocytes, monocytes and a fraction of granulocytes. The monoclonals discussed are compared with the monoclonals for identification of leucocyte differentiation antigens (cluster of differentiation) characterized on the 1st Int. Workshop on Human Leucocyte Differentiation Antigens (Paris, 1982). PMID- 6240939 TI - Therapeutic percutaneous renal artery occlusion with a detachable balloon. AB - Bilateral nephrectomy is sometimes required for the control of severe hypertension or nephrotic syndrome. Surgical intervention in a patient with uncontrollable hypertension or the malnutrition and anasarca of nephrotic syndrome is associated with increased risk for the development of operative complications. We report 2 hemodialysis patients, 1 with uncontrollable hypertension and 1 with nephrotic syndrome, who were successfully treated with percutaneous renal infarction. Inflatable and detachable balloons were placed in each renal artery by percutaneous arterial catheterization. Neither patient experienced any significant complication from the procedure. PMID- 6240940 TI - Differences in the mean fat cell diameter of males between 1 and 48 months of age. AB - The mean fat cell diameter was determined from measurements of abdominal adipose cells, obtained during inguinal hernia repair, of 126 white and 95 black males ranging in age from 1 through 48 months of age. The mean diameters of black and white subjects did not differ significantly, suggesting that differences in fatness among adults of these two ethnic groups have their origin beyond the age range of this study. The mean fat cell diameter increased through the 6-8 month age group, decreased until the end of the first year, and then levelled off through 48 months of age. Comparison of this curve with those for the triceps, subscapular, abdominal, and suprailiac skinfolds of the same subjects showed generally parallel courses except for the triceps, which continued to increase in size after the means of fat cell diameters and the other skinfolds had levelled off. Our data indicate that changes in body fatness on the trunk at least in the first 4 years of life may be accounted for by changes in fat cell size. PMID- 6240941 TI - [Survey of local anesthesia for the mandibular first molar]. PMID- 6240942 TI - [Anesthetic management in mentally handicapped patients for dental procedures]. PMID- 6240943 TI - [Diagnostic value of laparoscopy in patients with infertility and oligomenorrhea]. PMID- 6240944 TI - The structure of the shell membrane, the development and structural change of the amnion and chorioallantoic membrane during hatching in the goose. PMID- 6240945 TI - [Histochemical and morphometric studies of the cranial tibial muscle in dogs of different dynamic aptitudes (greyhound, German shepherd and fox terrier)]. PMID- 6240946 TI - Equine limb anatomy: peroneus tertius muscle relationships. PMID- 6240947 TI - On the histochemistry of the seminiferous tubules and their terminal segments in the ram testis. PMID- 6240948 TI - Some observations on the morphology of the pigeon's seminiferous epithelium cells. PMID- 6240949 TI - Arteria maxillaris of the donkey (Equus asinus). PMID- 6240950 TI - [Arterial vascularization of the porcine thymus in the 2d half of the prenatal period]. PMID- 6240951 TI - Anatomic study of the veins and the arteries of the penis of the camel (Camelus dromedarius). PMID- 6240952 TI - [Histological studies of retroperitoneal lymphatic vessels in Cebus apella]. PMID- 6240953 TI - Colonization and persistence of Escherichia coli in axenic and monoxenic turkeys. AB - Sites of colonization and persistence of virulent (O78) and avirulent (O2) Escherichia coli were determined in 3-week-old axenic turkeys. Colonization of O78 in turkeys infected with Streptococcus faecalis was also determined. Colonization and persistence of E coli in the intestinal tract and lung were not correlated with virulence. Both serotypes persisted in high titer in crop, ileum, ceca, colon, and lung. Persistence of E coli in the liver was positively correlated with virulence, although both serotypes were recovered from the liver in the absence of bacteremia, indicating possible intestinal translocation of E coli to the liver. A reduction in intestinal colonization and translocation of O78 was determined in monoxenic turkeys infected with S faecalis. In contrast, S faecalis had no effect on lung titers of O78. Air sacculitis, pericarditis, and pneumonia were observed in axenic and monoxenic turkeys infected with O78. Bacteremia was detected in a turkey exposed to O78. PMID- 6240954 TI - Effects of local anesthetics on healing of abdominal wounds in rabbits. AB - The influence of lidocaine and bupivacaine on the breaking strength and histopathologic appearance of wounds in the ventral abdominal midline (linea alba) of rabbits was studied. In control rabbits, group 1 (n = 24), skin and subcutaneous tissues were incised, permitting direct infiltration of the linea alba with normal saline solution. The linea alba was then incised, and wound margins were apposed in layers, using absorbable suture material. Group 2 rabbits (n = 24) were given 0.5% lidocaine, group 3 rabbits (n = 24) were given 2% lidocaine, and group 4 rabbits (n = 24) were given 0.5% bupivacaine, rather than saline solution. Eight rabbits from each group were killed 6, 12, and 18 days after wounding. Eight 1.0-cm wide transverse strips were removed from the abdominal wall of each rabbit. Two strips were used for histopathologic evaluation and 6 were tested for failure, using a mechanical testing device. Breaking strengths in group 1 averaged 0.66 kg, 1.35 kg, and 1.57 kg at 6, 12, and 18 days, respectively. None of the test groups had significantly different (P greater than 0.05) breaking strength results as compared with that in controls. The histopathologic appearance of tissues infiltrated with local anesthetics did not vary consistently from that of tissues infiltrated with normal saline solution. Local infiltration of lidocaine and bupivacaine does not alter substantially the healing of midline abdominal incisions in rabbits. PMID- 6240955 TI - The production of alpha-cyclodextrin by enzymatic degradation of starch. AB - The maximum concentration of alpha-cyclodextrin for the enzymatic degradation of starch is limited to about 13.5 g X 1(-1). By addition of decanol, the equilibrium of the reaction system can be shifted towards an alpha-cyclodextrin yield of 50% even at high substrate concentrations. The main variables of the decanol process--pH, temperature, substrate quality, substrate, and enzyme concentration--have been studied. The cyclodextrin-glycosyltransferase from Klebsiella pneumoniae M5 al can preferentially be employed at pH 6 to 8, temperatures of 40 to 50 degrees C and a decanol concentration of 0.1 kg-1 starch. The dextrose equivalent of starch is important with respect to the maximum achievable starch concentration, but not with respect to the reaction. Under process conditions, the rate of alpha-cyclodextrin evolution is limited by the enzymatic reaction and not by mass transfer of decanol into the aqueous phase. PMID- 6240956 TI - [Cutaneous lesions induced by long-term use of hydroxyurea]. AB - The authors report 3 cases of patients having myeloid chronic leukemia presenting skin changes after long-term hydroxyurea therapy. Some of these side effects are already known; such as dryness, pigmentation, spontaneous necrotizing ulceration and chromonychia with longitudinal pigmented bands. Two new signs are described: a band-like erythema on the dorsum of the fingers and toes, as in dermatomyositis and a plantar keratoderma which interpretation is difficult in such a context. The hydroxyurea's imputability is discussed. These lesions altogether are very suggestive of skin changes after hydroxyurea therapy. The occurrence of such phenomena is quite frequent. PMID- 6240957 TI - [A case of dermatosis papulosa nigra in a white man]. PMID- 6240958 TI - [Eruption of fleshy nodules during treatment with isotretinoin]. PMID- 6240959 TI - Recurrent macromastia after subcutaneous mastectomy. AB - Management of sudden unrelenting breast growth in a young woman included use of antiestrogen hormone therapy and subcutaneous mastectomy. Later, massive breast growth again occurred during pregnancy, requiring a repeat postpartum subcutaneous mastectomy. The dramatic response to a specific antiestrogen agent and the subsequent massive regrowth of breast tissue after subcutaneous mastectomy suggests that breast tissue is extremely sensitive to circulating hormones in certain patients with macromastia. The unusual nature of this patient's recurrent macromastia warrants this review of reports of similarly affected patients and discussion of general concepts in the medical and surgical management of the disorder. PMID- 6240960 TI - A controlled comparison of the Pomeroy resection technique and laparoscopic electrocoagulation of the tubes. AB - The Pomeroy resection technique and laparoscopic electrocoagulation of the tubes are compared in a controlled study. Information was obtained during the patients' stay in hospital and at three and 12 months after operation. There were no significant differences between the study groups concerning age, social group, parity, contraceptive practices or age of the children. The surgery time, stay in hospital, periods of postoperative discomfort and sick leave were shorter in the laparoscopy group, and there were fewer postoperative complaints than in the laparotomy group. No differences in the impact on postoperative bleeding patterns were demonstrated. PMID- 6240961 TI - Diagnostic importance of immunological markers in lymphoma involving the central nervous system. AB - In an elderly woman, lymphoma involved the central nervous system and unusual nonlymphoreticular sites. Cerebrospinal fluid cell surface marker studies revealed a clone of malignant B cells. Studies of peripheral blood demonstrated a systemic disturbance of immune regulation similar to Epstein-Barr virus infections and the acquired immunodeficiency syndrome. PMID- 6240962 TI - In vitro activity and human pharmacokinetics of teicoplanin. AB - The in vitro activity of teicoplanin, a new antibiotic related to vancomycin, was determined against 456 gram-positive cocci. The activity of teicoplanin in comparison with that of vancomycin was similar against staphylococci but 4 to 40 times higher against enterococci and beta-hemolytic and viridans streptococci. The single-dose pharmacokinetics of teicoplanin were studied in six healthy volunteers after administration of 3 and 6 mg/kg intravenously and of 3 mg/kg intramuscularly. The kinetic parameters after both intravenous doses were very similar. The curves for concentration in plasma for the 3- and 6-mg/kg intravenous doses showed a triexponential decline with elimination half-lives of 47.3 and 44.1 h, respectively. The percentages of the doses recovered in urine (0 to 102 h) were 43.2 and 44.1%, respectively. The areas under the plasma curves were dose related: 256.5 and 520.9 micrograms/h per ml, respectively. The bioavailability of teicoplanin after injection of 3 mg/kg intramuscularly was 90%, and the peak level was 7.1 micrograms/ml. The mean levels in plasma 24 h after the 3-mg/kg doses were 2.1 and 2.3 micrograms/ml, respectively, and the mean level in plasma 24 h after the 6-mg/kg intravenous dose was 4.2 micrograms/ml. PMID- 6240964 TI - Glycogen synthesis by cell-free extracts from the dimorphic yeast Candida albicans. AB - A particulate glucosyltransferase prepared from budding and filamentous cultures of Candida albicans used uridine diphosphate glucose as sole glucosyl donor in a reaction (measured by following the incorporation of [14C]-glucose from UDP [14C] glucose into polymer) stimulated by glucose-6-phosphate and inhibited by adenosine triphosphate and guanosine triphosphate. The radiolabelled reaction product was solubilized by alpha-amylase, and, on oxidation with periodate followed by reduction with borohydride and acid hydrolysis, yielded erythritol and glycerol in the ratio of 4 to 1. The radiolabelled glucosyl residues were attached to an endogenous acceptor of high molecular weight. PMID- 6240963 TI - Teicoplanin, a new antibiotic from Actinoplanes teichomyceticus nov. sp. AB - Teicoplanin, a new glycopeptide antibiotic belonging to the same family as vancomycin, inhibits cell wall synthesis in Bacillus subtilis; the inhibition is accompanied by an intracellular accumulation of UDP-N-acetyl-muramyl pentapeptide. A cell-free system from Bacillus stearothermophilus, capable of synthesizing peptidoglycan, is 50% inhibited by teicoplanin at 40 micrograms/ml and 100% inhibited at 100 micrograms/ml; suppression of peptidoglycan synthesis is accompanied by parallel accumulation of the lipid intermediate. Teicoplanin binds to cell walls and forms a complex with N,N'-diacetyl-L-lysyl-D-alanyl-D alanine. The association constant of this complex is 2.56 X 10(6) liters mol-1, calculated by spectrophotometric titration. The mechanism of action of teicoplanin is discussed in comparison with those of other inhibitors of cell wall biosynthesis, namely, vancomycin, ristocetin, and gardimycin. PMID- 6240965 TI - Effects of gross motor activities on the severe self-injurious tantrums of multihandicapped individuals. AB - The present study assessed the effects of gross motor activities on the self injurious tantrums of three multihandicapped subjects. The tantrums did not seem related to specific environmental events and were rather infrequent, yet very severe. The study was carried out according to a withdrawal (ABAB) design. During baseline, the subjects executed routine activities that required minimal physical effort. During treatment, they performed gross motor activities that required considerable physical effort. These activities were designed to provide a wide variety of sensory (e.g., tactile, proprioceptive) input, but without tiring the subjects excessively. They were implemented when the subjects were in a quiet state. The results showed that concomitant with treatment, all subjects had a definite decline in the rate of self-injurious tantrums. Two subjects also exhibited a reduction in the duration of the tantrums. PMID- 6240966 TI - Bone and joint symptoms in Paget's disease. AB - Fifty patients with Paget's disease of bone were reviewed with regard to the basis of their symptoms and the long-term results of treatment. Twenty-four patients (48%) presented with pain localised within bone, while 17 (34%) presented with symptoms of degenerative joint disease. Three patients presented with bone pain and arthritis and the remaining six with fractures, ataxia, or painless deformity. Symptomatic osteoarthritis of the hip (OA) developed in 25 patients (50%) with approximately half developing radiological changes identical to those of idiopathic OA. Among the other patients those with coxa vara tended to show medial (rather than superior) joint space narrowing and severe Paget's disease on both sides of the joint. Arthritic pain, stiffness, and reduced mobility in other joints (knee, ankle, and wrist) were associated clinically with bone deformity adjacent to the affected joint and radiologically with distorted articular surfaces and narrowed joint spaces; sclerosis, subarticular cyst formation, and osteophytosis were usually absent. Fifteen patients were treated with calcitonin for bone pain alone; all claimed long-term 'good to complete' relief. By contrast, none of the 14 with arthritic symptoms responded to calcitonin when assessed retrospectively. Results of surgical and other medical treatment were analysed. Careful clinical evaluation is a prerequisite for optimal treatment in Paget's disease. PMID- 6240967 TI - Lack of an effect of drugs acting at histamine receptors on norepinephrine induced relaxation of porcine coronary arteries. AB - The effects of selective histamine receptor stimulation on relaxation to norepinephrine (NE) were determined in four sizes of spirally cut porcine coronary arteries. The four sizes of porcine coronary artery were designated very large (greater than 4.0 mm o.d.), large (1.5-2.5 mm o.d.), medium (0.8-1.2 mm o.d.), and small (less than or equal to 0.5 mm o.d.). Histamine, dimaprit, 2 pyridylethylamine, and histamine plus either mepyramine or metiamide did not alter the concentration-response curve to NE. Thus histamine receptor stimulation does not change relaxations of porcine coronary arteries to NE. PMID- 6240968 TI - [Data on the echocardiogram, pressure profile during exertion, and ambulatory blood pressure measurements in borderline arterial hypertension]. AB - Comparative study is performed between echocardiographic measurements (TM), exercise test blood pressure profile (ETP) and ambulatory blood pressure load (BPL) in 26 borderline hypertensive subjects (19 males, 7 females). An abnormal ETP is found for 15 subjects (57 p. 100), an abnormal BPL for 10 subjects (38 p. 100). The diastolic interventricular septum thickness (IVS) and the diastolic posterior wall thickness (PWT) are abnormal (greater than 11 mm) for 6 and 3 subjects. Patient with pathologic ETP or/and BPL have greater IVS and PWT than other subjects (p less than 0,001). A good correlation is found between individual activity systolic blood pressure or 24 hours systolic blood pressure means values and PWT, IVS or left ventricular mass. These 3 examinations lead to a better assessment of cardiovascular strain and allow a better diagnosis and therapeutic approach in borderline hypertensive patients. PMID- 6240969 TI - [Effect of experimental myocardial hypertrophy on coronary microcirculation in the rat]. AB - Effects of cardiac hypertrophy on coronary capillary density and volume have been studied in two models: systemic hypertension (1c. 2K Goldblatt model, n = 27), and volume overload (aorto-caval fistula, n = 27) compared to a control group (n = 27). Studies have been performed at 1 month, 3 and 6 months. Subendocardial and subepicardial coronary capillaries have been visualized by in injection of fluorescein-labeled dextran (FITC). The body weights were not significantly different in the three groups. The heart weight was the same in hypertensive model and fistula. Goldblatt model was associated with a high blood pressure and an increase in left ventricular wall thickness, whereas fistula was associated with a lower blood pressure and no difference in wall thickness as compared to controls. No difference in subepicardial capillary density was found in the three groups, whereas the subendocardial capillary density was decreased in the two models of cardiac hypertrophy (-25%). Capillary area and mean perimeter, were increased in fistula, due to vasodilatation, and decreased in Goldblatt model in relation to vasoconstriction. PMID- 6240970 TI - [Binding of aldosterone to its receptors along the nephron of the normal and spontaneously hypertensive rat]. AB - The specific binding of aldosterone has been investigated using an autoradiographic method, on isolated tubular segments of kidneys from spontaneously hypertensive (SHR) and normotensive (KWR) Okamoto rats, and normotensive Wistar (NWR) rats. A low, mineralocorticoid, concentration of aldosterone (2 X 10(-9) M) was used. In proximal tubules, almost no specific labelling was found in the three groups. In the cortical ascending limb, a specific nuclear labelling was present and equivalent in the three groups. In the distal (DCT) and cortical collecting (CCT) tubule, the specific labelling was double in SHR and KWR than in NWR. This higher binding capacity occurs in target segments for aldosterone, and coincides with the increased sodium reabsorption in the distal structures of Okamoto rats, previously reported by our laboratory. The relations between these observations and the altered membrane permeability described in hypertensive disease is discussed. PMID- 6240971 TI - An office protocol for treating patients with hypertensive disease. PMID- 6240972 TI - A directory of dental services for the disabled. PMID- 6240973 TI - Deacylation rate constants of acylated human and porcine plasmins. AB - Deacylation rate constants, k3, were measured for the human acyl-plasmins which contain in the acyl portion, RCO, the R groups methyl, cyclohexyl, p-nitrophenyl, isobutyl, trans-isopropenyl, phenyl, alpha-naphthyl, anisoyl and p guanidinophenyl. Values of k3 were also determined for the porcine acyl-plasmins which have R = methyl, cyclohexyl, phenyl, anisoyl and p-guanidinophenyl. In general, for both the human and porcine acyl-plasmins, k3 decreased as the electron-donating ability of the acyl group increased. At 25 degrees C, the human acyl-plasmin with R = methyl has the highest k3, 1.06 +/- 0.05 X 10(-2) s-1, and the porcine acyl-plasmin with R = p-guanidinophenyl the lowest k3, 1.4 +/- 0.1 X 10(-6) s-1. PMID- 6240974 TI - An experimental study on the effects of the MORA on football players. PMID- 6240975 TI - Cranio-cervico-mandibular dysfunction: an overview and hopeful aid to the general dentist. PMID- 6240976 TI - The interaction of IgG with Fc gamma receptors on human neutrophils. AB - The interaction of IgG with Fc gamma receptors on human PMN was studied by investigating the capacity of IgG and some of its fragments to mediate and inhibit, respectively, binding of immune complexes to these receptors and the subsequent activation of the cells. Fragments included Fab/Fc which is monovalent but contains the complete Fc region, Facb (divalent, C gamma 3 domains removed), Fc, pFc' (a C gamma 3 dimer) and a peptide corresponding to the greater part of one C gamma 2 domain (amino acids 278 through 333) including the carbohydrate side chains. F(ab')2 and Fab served as controls. The results indicate that human IgG interacts with human PMN Fc receptors predominantly through its C gamma 2 domains, while binding of rabbit IgG involves additional sites in C gamma 3. The C gamma 2 binding site on human IgG appears to be located between those for C1 and protein A and to contain lysine residues. For its correct exposure the C gamma 2 domains must be kept in the native conformation, in which both the hinge disulfide bridges and the carbohydrate moieties are involved. A role of the sugars in the actual binding, on the other hand, can be excluded. PMID- 6240977 TI - Phagocytosis of immune complexes by human neutrophils and monocytes: relative importance of Fc and C3b receptors. AB - Human neutrophils and peripheral blood monocytes were studied for their Fc- and C3b-receptors after incubation of the cells with two types of immune complexes (IgG or F(ab')2. Immune complexes can bind to and activate phagocytes via Fc- and C3b-receptors. On mononuclear phagocytes an additional receptor is found that is able to interact directly with F(ab')2-complexes. C3b- and Fc-receptors can mediate ingestion of appropriately opsonized particles, C3b-receptors being at least as efficient as Fc-receptors. The extents of cell activation and phagocytosis in vitro depend on a number of variables, like complex size, ligand (antibody, C3b) density on the surface of opsonized particles, receptor number etc., which are not controlled in most studies and thus may explain the discrepant results reported in the literature. With the in vitro results obtained here, we cannot fully explain in vivo data obtained by various groups, where F(ab')2 antibodies yielded full protection against different types of infections. Therefore, great caution must be applied in all attempts to extrapolate in vitro data to the actual situation in vivo. PMID- 6240978 TI - Acyl-CoA synthetase and the peroxisomal enzymes of beta-oxidation in human liver. Quantitative analysis of their subcellular localization. AB - The presence of acyl-CoA synthetase (EC 6.2.1.3) in peroxisomes and the subcellular distribution of beta-oxidation enzymes in human liver were investigated by using a single-step fractionation method of whole liver homogenates in metrizamide continuous density gradients and a novel procedure of computer analysis of results. Peroxisomes were found to contain 16% of the liver palmitoyl-CoA synthetase activity, and 21% and 60% of the enzyme activity was localized in mitochondria and microsomal fractions respectively. Fatty acyl-CoA oxidase was localized exclusively in peroxisomes, confirming previous results. Human liver peroxisomes were found to contribute 13%, 17% and 11% of the liver activities of crotonase, beta-hydroxyacyl-CoA dehydrogenase and thiolase respectively. The absolute activities found in peroxisomes for the enzymes investigated suggest that in human liver fatty acyl-CoA oxidase is the rate limiting enzyme of the peroxisomal beta-oxidation pathway, when palmitic acid is the substrate. PMID- 6240980 TI - Influence of inorganic phosphate on the kinetic properties of yeast phosphofructokinase. AB - Yeast phosphofructokinase is effectively activated by inorganic phosphate. In the absence of other allosteric stimulators, inorganic phosphate increases the maximum activity of the enzyme only. In the presence of the activators AMP and fructose 2,6-bisphosphate inorganic phosphate causes changes in the maximum activity and the enzyme affinity to fructose 6-phosphate. Inorganic phosphate augments the sensitivity of phosphofructokinase to the activators AMP and fructose 2,6-bisphosphate and increases the respective maximum activities. The extent of activation of the enzyme by inorganic phosphate prevails at low levels of fructose 6-phosphate and high ATP concentrations. PMID- 6240979 TI - Difference in glucose sensitivity of liver glycolysis and glycogen synthesis. Relationship between lactate production and fructose 2,6-bisphosphate concentration. AB - Incubation of isolated rat hepatocytes from fasted rats with 0-6 mM-glucose caused an increase in [fructose 2,6-bisphosphate] (0.2 to about 5 nmol/g) without net lactate production. A release of 3H2O from [3-3H]glucose was, however, detectable, indicating that phosphofructokinase was active and that cycling occurred between fructose 6-phosphate and fructose 1,6-bisphosphate. A relationship between [fructose 2,6-bisphosphate] and lactate production was observed when hepatocytes were incubated with [glucose] greater than 6 mM. Incubation with glucose caused a dose-dependent increase in [hexose 6 phosphates]. The maximal capacity of liver cytosolic proteins to bind fructose 2,6-bisphosphate was 15 nmol/g, with affinity constants of 5 X 10(6) and 0.5 X 10(6) M-1. One can calculate that, at 5 microM, more than 90% of fructose 2,6 bisphosphate is bound to cytosolic proteins. In livers of non-anaesthetized fasted mice, the activation of glycogen synthase was more sensitive to glucose injection than was the increase in [fructose 2,6-bisphosphate], whereas the opposite situation was observed in livers of fed mice. Glucose injection caused no change in the activity of liver phosphofructokinase-2 and decreased the [hexose 6-phosphates] in livers of fed mice. PMID- 6240981 TI - Inhibition of glucokinase in hepatocytes by alloxan. AB - The effect of alloxan on glucokinase in isolated rat hepatocytes was studied. Exposure of hepatocytes to alloxan (3 mM) at 30 degrees C for 5 min produced a marked inhibition (77%) of glucokinase activity and altered slightly the phosphofructokinase activity (32% inhibition). Pyruvate kinase and glucose 6 phosphate dehydrogenase, however, were not inhibited at all. Alloxan induced a concentration-dependent inhibition of glucokinase activity with a detectable inhibition at an alloxan concentration of 1 mM. The inhibition of glucokinase activity by alloxan was protected by the simultaneous presence of 15 mM hexose such as D-glucose, 3-O-methylglucose, or D-mannose. D-Galactose showed no protective effect. These results suggest that alloxan may exert its cytotoxic action through the inhibition of glucokinase activity not only in the liver but also in the pancreatic islets, since liver and islet glucokinases are known to be quite similar in various properties. PMID- 6240982 TI - Caffeine-induced reorganization of DNA replicating system occurs on or near nuclear matrix in HeLa cells. AB - Since caffeine reorganizes the DNA replicating system, with several consequences, we studied the effect of caffeine on the DNA replication which normally occurs on or near the nuclear matrix in a variety of eukaryotic cells. When HeLa cells, treated with or without the DNA-damaging agent, neocarzinostatin, were postincubated in the presence or absence of caffeine and then pulse-labeled with [3H]thymidine, the DNA remaining tightly associated with the matrix was enriched in the newly synthesized DNA at the same level as that seen in untreated cells. The nuclear matrix-bound DNA polymerase alpha activity was also the same in these cells. Therefore, in the presence of caffeine, DNA replication, with or without DNA damage, also occurs on or near the nuclear matrix, as is the case in normal DNA replication. PMID- 6240983 TI - Bacteriophage phi X 174 A protein binds in vitro to the phage phi X 174 DNA by a phosphodiester bond via a tyrosine residue. AB - Nuclease digestion of the phi X 174 A* protein covalent complex with /P32/ - phi X 174 phage DNA results in the transfer of 32p-label to the protein. Acid hydrolysis of the 32p-labelled A* protein yields (4)0-phosphotyrosine. PMID- 6240984 TI - Effect of patent ductus arteriosus on lower extremity blood flow velocity patterns in preterm infants. AB - We used a 20-MHz, range-gated, pulsed Doppler device to measure noninvasively femoral artery blood flow velocity patterns in 24 preterm infants with patent ductus arteriosus (PDA). Mean spatial flow velocity and its temporal average were recorded by illumination of the entire flow stream. Peak systolic forward flow velocity (Vs), peak diastolic retrograde flow velocity (VD), mean flow velocity (Vf), and the peak to peak-mean velocity ratio, (VS-VD)/Vf, were determined serially in each patient. The changes in the femoral flow velocity pattern preceded or coincided with other evidence of ductal left to right shunting. Prior to PDA closure, (VS-VD)/Vf averaged 14.1 and Vf averaged 4.4 cm/sec; after ductal closure, (VS-VD)/Vf fell to 3.7 (P less than .001) and Vf rose to 9.1 cm/sec, more than twice the preclosure value (P less than .001). Large diastolic reverse flow velocity vectors and low mean velocity correlated with large left to right PDA shunts estimated from other methods of assessment. The noninvasive femoral artery Doppler approach detects patency of the ductus early in life, reflects left to right shunting in diastole, and emphasizes the impact of the PDA on systemic blood flow. PMID- 6240985 TI - [Glucose 1,6-diphosphate in the erythrocytes of various species of mammal]. AB - Red blood cells from human, pig, cow, rabbit, rat and sheep were investigated for the occurrence of phosphoglucomutase multiple forms, G1,6P2 level, PGM, PRM and G1,6P2 synthetic activities. In all cases a species specific pattern of PGM isoenzymes was detected by starch gel electrophoresis. G1,6P2 mean values range from 33 to 122 nmol/ml RBC for pig and rabbit erythrocytes, respectively. The study of the correlation between the biphosphate content and the occurrence of the three measured enzymatic activities indicates a possible role of PRM activity (property of PGM2 isoenzymes) in the erythrocytic G1,6P2 catabolism. PMID- 6240986 TI - [Degradative pathways of glucose 1,6-diphosphate in human erythrocytes]. AB - In this study human erythrocytes have been incubated with various effectors most of which able to decrease the G1, 6P2 content. By using haemolysates and partially purified phosphoglucomutase isoenzymes we provide evidence that the G1, 6P2 decrease can be attributed to the ability of phosphoglucomutase PGM2 isoenzymes to mutate various sugar monophosphates. These isoenzymes, phosphorylated by G1, 6P2, may transfer the phosphate group to monophosphate sugars thus releasing the respective bisphosphate. PMID- 6240987 TI - Effects of antidepressants on skilled performance. AB - Effects of amitriptyline 50 mg, desipramine 100 mg, and zimelidine 200 mg alone and in combination with ethanol 0.8 g/kg were investigated in healthy, male volunteers. Amitriptyline increased body sway and impaired tracking as well as information processing. It had an additive deleterious pharmacodynamic interaction with ethanol. Desipramine and zimelidine were free of adverse effects on performance and did not have significant interactions with ethanol. The dose of ethanol used in the present study did not inhibit biotransformation of the antidepressants. PMID- 6240988 TI - Structural mapping of chloroplast coupling factor. AB - Fluorescence resonance energy transfer measurements have been used to investigate the spatial relationships between the nucleotide binding sites and the gamma subunit of the H+-ATPase from chloroplasts and the orientation of these sites with respect to the membrane surface. Fluorescent maleimides reacted covalently at specific sulfhydryl sites on the gamma-subunit served as energy donors. One sulfhydryl site can be labeled only under energized conditions on the thylakoid membrane surface (light site). The two gamma-sulfhydryls exposed after catalytic activation served as a second donor site (disulfide site). In one set of experiments, the nucleotide analogue 2'(3')-(trinitrophenyl)adenosine triphosphate, selectively bound at each of the three nucleotide binding sites of the solubilized coupling factor, was used as an energy acceptor; in another, octadecylrhodamine with its acyl chain inserted in the vesicle bilayer and the rhodamine fluorophore exposed along the membrane surface was the energy acceptor. The distance between the sulfhydryl and disulfide sites was also obtained by sequentially labeling the sites with coumarin (donor) and fluorescein (acceptor) maleimide derivatives, respectively. The results indicate that all three nucleotide sites are approximately equal to 50 A from the light-labeled gamma sulfhydryl. Two of the nucleotide sites are very far from the gamma-disulfide (greater than 74 A), while the third site, which binds nucleotides reversibly under all conditions, is 62 A from this sulfhydryl. The light-labeled sulfhydryl and disulfide sites are about 42-47 A apart. Finally, the distance of closest approach between the membrane surface of the reconstituted system and the gamma disulfide is 31 A.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 6240989 TI - Effect of skeletal muscle myosin light chain 2 on the Ca2+-sensitive interaction of myosin and heavy meromyosin with regulated actin. AB - A low-speed centrifugation assay has been used to examine the binding of myosin filaments to F-action and to regulated actin in the presence of MgATP. While the cross-linking of F-actin by myosin was Ca2+ insensitive, much less regulated actin was cross-linked by myosin in the absence of Ca2+ than in its presence. Removal of the 19000-dalton, phosphorylatable light chain from myosin resulted in the loss of this Ca2+ sensitivity. Readdition of this light chain partially restored the Ca2+-sensitive cross-linking of regulated actin by myosin. Urea gel electrophoresis has been used to distinguish that fraction of heavy meromyosin which contains intact phosphorylatable light chain from that which contains a 17000-dalton fragment of this light chain. In the absence of Ca2+, heavy meromyosin which contained digested light chain bound to regulated actin in MgATP about 10-fold more tightly than did heavy meromyosin which contained intact light chain. The regulated actin-activated ATPases of heavy meromyosin also showed that cleavage of this light chain causes a substantial increase in the affinity of heavy meromyosin for regulated actin in the absence of Ca2+. Thus, the binding of both myosin and heavy meromyosin to regulated actin is Ca2+ sensitive, and this sensitivity is dependent on the phosphorylatable light chain. PMID- 6240990 TI - Human erythrocyte phosphoglucomutase: comparison of the kinetic properties of PGM1 and PGM2 isoenzymes. AB - Kinetic properties of PGM1 and PGM2 phosphoglucomutase "primary" isoenzymes from human erythrocytes were studied. The two enzyme forms share a "ping-pong" kinetic mechanism and show similar Km for substrate (glucose 1-P) and cofactor (glucose 1,6-P2). Micromolar concentrations of fructose 1,6-P2 and glycerate 2,3-P2 inhibit both PGM1 and PGM2 isoenzymes to a similar extent. The sole PGM2 form is affected by ribose monophosphates (ribose 1-P and ribose 5-P) that act as mutase inhibitors vs. glucose 1,6-P2 and as apparent activators vs. glucose 1-P. The interaction between PGM2 isoenzyme and ribose monophosphates is discussed in the light of the ability of this form to also display phosphoribomutase activity. PMID- 6240991 TI - [Isolation and characteristics of actin-like proteins in liver mitochondria]. AB - Using affinity chromatography on DNAase I-Sepharose, an actin-like protein was isolated from rat liver mitochondria and purified 60-fold. SDS electrophoresis in polyacrylamide gel revealed that the protein migrated with muscle actin and thus had the molecular weight of 42 000 Da. Evidence for the actin-like nature of the mitochondrial protein could be obtained from the fact that the protein inhibited the activity of pancreatic DNAase I which, similar to the smooth muscle protein, was less conspicuous than that of its muscle counterpart. Unlike striated muscle actin but similar to the smooth muscle protein, the mitochondrial actin weakly stimulated the Mg-ATPase activity of rabbit skeletal muscle myosin. After manyfold washing of the mitochondria with isotonic isolation media, the content of the actin-like protein remained unchanged, which indirectly points to the presence of insignificant cytoplasmic actin contaminations. During isoelectrofocusing, the mitochondrial actin-like protein yielded two forms, i. e., beta- and gamma-isoactins, whose ratio was 8:1. The pI values for the beta- and gamma-isoforms were 5.52 and 5.59, respectively. The identical position of the absorption spectra (260 nm) and fluorescence excitation spectra (around 280 nm) maxima of the actin-like protein and smooth and skeletal muscle actins testify to their homology. PMID- 6240992 TI - [Several peculiarities of the purine-base fixation of the substrate in the active sites of myosin Ca2+-ATPase]. AB - A comparative study of kinetic parameters (Km and V) of hydrolysis by heavy meromyosin of several synthetic ATP analogs with substituents at positions N(1) and N(C6) of the purine ring was carried out. Analysis of changes in the Km values suggests that the purine base of ATP is fixed in the active center due to the formation of a hydrogen bond between N1 and the proton donor group of the protein as well as between the 6-NH2-amino group of the nucleotide and the proton acceptor group of the protein. It was shown that the rate of catalytic conversion of the substrate is determined by the mode of binding of its purine ring. Depending on the properties of the substituent radical, the latter either prevents the binding by causing little or no increase in the rate of hydrolysis or causes the displacement of the whole substrate molecule in the active center, which leads to the deceleration of hydrolysis. PMID- 6240993 TI - [Interaction of heavy and light chains of plasmin with fibrinogen E and D fragments]. AB - It was demonstrated that plasminogen and the plasmin heavy chain form a complex with an immobilized fibrinogen fragment E. The E-fragment interacts, in its turn, with the immobilized heavy chain; this interaction is provided for by the lysin binding sites of the plasminogen molecule. The plasmin light chain having no lysin binding sites is specifically absorbed on the immobilized fragment D, whereas the D-fragment--on the immobilized light chain. The elution is caused by arginine or benzamidine; 6-aminohexanoic acid does not affect this interaction. It is assumed that the interaction of plasminogen and plasmin with fibrin is provided for not only by the lysine binding but also by the benzamidine binding sites of the plasminogen molecule. PMID- 6240994 TI - Inhibition of human placental progesterone synthesis by danazol in vivo. AB - In vivo, a single dose of 1000 mg danazol was given orally to pregnant volunteers (n = 8) prior to a therapeutic abortion (8th-12th week of gestation). Changes in serum progesterone and estradiol were evaluated both by analysis of percentage values related to initial concentrations or statistically by a Kruskal-Wallis test comparing absolute steroid concentrations. Following treatment (n = 8), a significant decrease in mean plasma progesterone of about 20% was observed within 2-4 hours; progesterone levels varied between 80-120% during 24 hours in controls (n = 10); individual serum estradiol decreased up to 30% of control values 2 hours after danazol application. Changes in estradiol in controls versus tests were not statistically significant (p less than 0.05) when absolute estradiol concentrations were compared. Only a slight (10-20%) decrease in mean serum DHAS was found between 2 to 6 hours following danazol treatment. This study demonstrates the inhibitory activity of danazol on the human maternal and fetal steroidogenesis in vivo. The possible sites of action of danazol are discussed. PMID- 6240995 TI - Plasminogen activator and nuclear androgen receptor in rat prostate tumors after treatment with D-Trp-6-LH-RH. AB - Plasminogen activator and nonspecific proteolytic activity in transplantable squamous cell rat prostate tumor 11095 were measured by a fluorometric method. Prostate tumors which regressed after treatment with D-Trp-6-LH-RH had 10-fold lower concentrations of plasminogen activator(s) per mg of protein, and considerably higher levels of nuclear androgen receptor. On the other hand, there were no significant changes in nonspecific proteolytic activity in tumor tissue between untreated and D-Trp-6-LH-RH treated rats. The prostate tumor had at least three different plasminogen activator-like bands, as determined by polyacrylamide gel electrophoresis with plasminogen as substrate. The decreased activity of plasminogen activator(s) and considerably higher levels of nuclear androgen receptors correlate with the regression of prostate tumors induced by the treatment of rats with D-Trp-6-LH-RH. PMID- 6240996 TI - Comparative microscopic study of cardiotoxicity and skin toxicity of anthracycline analogs. AB - Golden hamsters were submitted, three times a week during 4 weeks, to i.p. administration of an antracenedione, mitoxantrone (MTX), and 12 different anthracyclines, adriamycin (ADM), detorubicin (DTR), daunorubicin (DNR), 4'-epi adriamycin (e-ADM), rubidazone (RBZ), aclacinomycin (ACM), N trifluoroacetyladriamycin-14-valerate (AD-32), tetrahydropyranyl-adriamycin (THP ADM), N-L-leucyl-daunorubicin (l-DNR), carminomycin (CAM), rubicyclamin (RBC) and N-trifluoroacetyl-adriamycin-14-9-hemiadipate (AD-143), at doses equivalent to 3/4 those which are optimally oncostatic on murine L1210 leukemia. The electron microscopic (EM) study of the myocardium showed that all studied drugs are cardiotoxic, but with different degree of cardiotoxicity. The histopathological study of the skin detect degenerative lesions with different degree of alopecia. According to the degree of their cardiotoxicity, skin toxicity, and general toxicity or mortality, all drugs studied are classified into 3 groups: 1st group, ADM, DNR, 1-DNR and RBZ, causing very severe cardiac alterations and alopecia (grade 2-3), and very high mortality, 2nd group, e-ADM, DTR, CAM RBC and MTX, with less severe cardiac alterations, and alopecia (grade 1-2), and always high mortality, and 3rd group, ACM, THP-ADM, AD-32 and AD-143, causing less severe myocardial alterations (grade 1-2), without alopecia (grade 0), and extremely low mortality and general toxicity. PMID- 6240997 TI - Preparation of a cell-free translation system from a wild-type strain of Neurospora crassa and translation of pyruvate kinase messenger RNA. AB - A cell-free in vitro translation system exhibiting high activity has been developed from wild-type Neurospora crassa mycelium. The isolation is simple and fast, and the homogenization does not appear to affect the activity of mycelial proteases and nucleases. This system is capable of supporting efficient translation of exogenously added homologous RNA as demonstrated by the experiments with PK-specific mRNA. In addition, it translates heterologous RNA efficiently, shown by the translation of globin mRNA. We did not examine the Neurospora lysate for post-translational modification activity. The procedure used for the preparation of Neurospora cell-free extracts should be readily applicable to the other filamentous fungi. PMID- 6240998 TI - Proteases in human tumors. AB - We carried on an investigation of proteases associated to human tumors by immunohistological techniques. Most of our work dealt with the plasmin system (plasminogen, its two activators and the two plasmin inhibitors, a 2 antiplasmin and a 2 macroglobulin). We found an antigen reacting with anti plasminogen serum in all the 30 colorectal adenocarcinomas we studied by immunofluorescence. This antigen was mainly plasminogen, as we could not detect active plasmin by a histochemical technique on sections of the same tumors. However it is likely that plasminogen present at the surface of tumor cells and on the contour of tumor foci, mainly in invasive areas, can be converted into plasmin, which in turn plays an important role in the degradation of basement membrane antigens. This makes easier tumor invasiveness and release of isolated tumor cells, ready for metastasizing. Plasmin action is likely of short duration and within short range, as this enzyme is rapidly neutralized by its inhibitors, both present at high concentration in the peritumoral stroma. Cathepsin B was characterized by immunoperoxidase method in many colorectal tumors. However our results are preliminary, so we cannot draw any conclusion on the role of this enzyme in tumor invasiveness. PMID- 6240999 TI - Cell cycle mutants of mammalian cells in culture. Present interest and limits to the study of thermodependent mutants. AB - Mammalian variants with a defect altering the cell cycle progression have been selected, characterized to different extents and preliminary genetic analysis has been carried out. The difficulties encountered in their study are discussed below. Up to now, they have limited the genetic approach to the cell cycle. PMID- 6241000 TI - Culture of chondrocytes in medium supplemented with fetal calf serum or a serum substitute: Ultroser G. AB - Fetal calf serum and a serum substitute, Ultroser G, were compared for their effects on the growth curves, clonal growth and cell cycle progression of rabbit chondrocytes in primary culture and during at least three cell passages and included a screen for the maintenance of cartilage-like differentiation i.e. the presence of type II collagen. Proliferation was also compared with another serum substitute, Nu-Serum. Ultroser G is shown to be equivalent to fetal calf serum as far as chondrocyte proliferation is concerned, clonal growth is improved and biosynthesis of type II collagen is maintained in primary culture. PMID- 6241001 TI - [Effect of prolactin on the secretion of milk casein: metabolism of arachidonic acid]. AB - Mammary gland fragments were incubated in the presence of prolactin and arachidonic acid which stimulate casein secretion. The effects of these stimuli in the presence of agents that influence arachidonic acid metabolism were investigated. Chloroquine, a blocker of phospholipase A2 activity, decreased prolactin but not arachidonic acid stimulation of casein secretion. Phospholipase A2 markedly stimulated casein secretion. Nordihydroguaiaretic acid (NDGA), an antioxidant that inhibits lipoxygenase, blocked the stimulating effect of prolactin and arachidonic acid. Ultrastructural studies indicated that phospholipase A2-induced stimulation of secretion was comparable to that of prolactin but that arachidonic acid-induced stimulation did not involve the same Golgi membrane modifications. These studies suggest that prolactin and phospholipase A2 stimulate secretion by a common way, and that arachidonic acid interferes with secretion by metabolic products of the lipoxygenase pathway. PMID- 6241002 TI - Opposite effects of glucocorticoid on estrogen-induced growth and differentiation of quail oviduct: demonstration by sequential treatments. AB - Control of the development and functions of avian oviduct is monitored by four classes of steroid hormones, including glucocorticoids. The effects of dexamethasone (DEX), a synthetic glucocorticoid, were studied via sequential treatments with estradiol benzoate, paying special attention to changes in estrogenic oviduct responses involving DNA synthesis and cell proliferation, ovalbumin accumulation and cell differentiation. DEX exerted an antagonistic effect upon estrogen stimulation when administered separately before or after estradiol benzoate (EB). Given before EB, DEX was more strongly antagonistic for DNA synthesis than when given simultaneously with EB. Administered after EB, DEX reversed EB-induced cell proliferation: the DNA content declined and the oviduct regressed. In the same way, protein and ovalbumin synthesis was inhibited and delayed by first intervention of DEX, and accelerated catabolism of ovalbumin and proteins was observed when DEX followed EB. DEX, which was ineffective alone, but synergistic on ovalbumin synthesis when given concomitantly with EB, prevented or dissipated the estrogenic effects, cell proliferation and secretory process when administered in sequential treatments. PMID- 6241003 TI - The cytoplasmic matrix of the human spermatozoon: cross-filaments link the various cell components. AB - This transmission electron microscopic study demonstrated a periodic arrangement of short cross-filaments in all the cytoplasmic layers of the human spermatozoon. These filaments were connected with adjacent cellular components (of the same type or not) thus appearing to link the sperm structures to one another. The filaments of the peripheral cytoplasm, those of the perinuclear space and those between the cytoskeletal structures of the flagellum were 3 to 5 nm, 7 to 9 nm and 2 to 4 nm wide respectively. These cross-links displayed a 14 to 20 nm periodicity and measured 6 to 35 nm in length, depending upon their location. They were associated with electron dense patches on the outer acrosomal membrane. Plasma membrane swelling was associated with a disruption of the cortical filaments on the inside surface of the membrane. This suggested a relation between the normal morphology of the plasmalemma and the cross-filaments. In altered sperm heads, a particular modification of the perinuclear space was found consisting of an aggregation of the cross-filaments into repeated bundles. Many of the morphological characteristics of these cross-filaments could be compared to similar cytoskeletal structures as known in somatic cells. The data of this study suggest that this filamentous network may play an essential role in the maintenance of the topographical relations between the various organelles which may be especially necessary due to the kinematics of this cell. PMID- 6241004 TI - Follicle cell tubular system in the prawn Macrobrachium rosenbergii: a route for exchanges between haemolymph and vitellogenic oocytes? AB - The epithelial cells of the ovary follicles have been studied in the prawn Macrobrachium rosenbergii using electron microscope and horseradish peroxidase. A network of circumvoluted and anastomosed tubules, measuring about 0.15 micron in diameter, communicates with the extracellular spaces. This tubular network is a structure which extensively increases the permeability of the follicular epithelium. PMID- 6241005 TI - [Micrometric in situ marking apparatus for an object on a microscope grid. Application of observation of serial sections]. AB - A device for the precise localization (better than 0.5 micron) of an object on a grid has been developed and connected to the translation system of an electron microscope. Applied to biological thin sections, this device enables to easily find and to observe a selected microcrystal projection obtained by the grid sectioning technique. Moreover, low dose observations on ribbons of ultrathin sections can be made because the information is repeated in the successive sections of the ribbon: With the device the position of the selected object is determined at high dose in one section and low dose measurement is made on the following section. PMID- 6241006 TI - Dynamics of zona pellucida formation by the mouse oocyte. An autoradiographic study. AB - The dynamics of the synthesis of the mouse oocyte zona pellucida was studied using light microscope autoradiography after intrabursal injection of (3H) fucose. Zona accretion occurred continuously from the inside, demonstrating that the oocyte itself elaborated all the raw material of the zona. The duration of zona synthesis corresponded to that of the oocyte growth phase. Zona secretion stopped one week before ovulation and there was no renewal of its material. PMID- 6241007 TI - Monoclonal antibodies binding to nuclear structures and axons in adult avian dorsal root ganglia. AB - Four monoclonal antibodies raised against embryonic chick dorsal root ganglia (5) recognize epitopes in neuronal and supporting cell nuclei, and in axons and contiguous cytoplasmic elements in some neurons of the adult chicken. Binding, analyzed at the ultrastructural level, is to reaction sites on the nuclear matrix, nucleolar complex, nuclear bodies, and filamentous elements in axons and some perikaryal regions. PMID- 6241008 TI - Marathon medicine and introduction. PMID- 6241009 TI - Wheelchairs and marathon road racing. PMID- 6241010 TI - Activity of muscle spindles, motor cortex and cerebellar nuclei during action tremor. AB - Repeated electrode penetration of the dentate and interpositus nuclei in a rhesus monkey transformed an 11-13 Hz physiologic tremor into a much larger action tremor at 5-7 Hz. This tremor was associated with muscle spindle spike train modulation and reflexly evoked tremor modulation of interpositus and motor cortex neurons as well as electromyogram (EMG). No tremor modulation was observed in spike trains recorded from dentate. The timing relationships of the spindle, EMG, and interpositus tremor discharges suggest that the interpositus plays a direct role in tremor suppression. Dentate, by contrast, may function indirectly by setting optimal transcortical long loop reflex dynamics concerned with intended voluntary movement. PMID- 6241011 TI - [Genetic heterogeneity and the diagnosis of hepatic glycogenoses]. AB - Glycogen storage diseases constitute a highly heterogeneous group of disorders, because of the many complex enzyme systems involved in glycogen metabolism, and also because of the diversity of molecular defects connected with gene mutations. To illustrate these features, the authors studied four types of liver glycogen storage diseases, respectively caused by deficiencies of glucose-6-phosphatase, debranching enzyme, phosphorylase and phosphorylase kinase. In each case, the role and functional characteristics of the enzyme system are described, as well as the bioclinical aspects of the deficiency. The only reliable way of diagnosing glycogen storage disease is by assaying the activity of the enzyme concerned. Assay procedure must take account of various factors, especially the progress made in understanding the nature and mechanism of action of enzyme systems, the possible tissular heterogeneity of the deficiency and the functional characteristics of certain enzymes. PMID- 6241012 TI - [Induction of thymidine kinase synthesis by 5-androstene-3 beta,17 beta-diol in the uterus of the immature rat]. AB - In uteri from immature female rats, thymidine kinase activity was largely increased by administration of 5-androstene-3 beta, 17 beta-diol. Kinetic studies showed that the enzyme activity reached its maximum level 30 h after hormone administration. That increase in thymidine kinase activity was dose-dependent and could be related to the synthesis of new molecules of enzyme. Moreover, it was exclusively observed in target-organs for estrogens. It was concluded that 5 androstene-3 beta, 17 beta-diol which results from the metabolism of dehydroepiandrosterone had estrogen-like properties with regard to the induction of thymidine kinase. PMID- 6241013 TI - [Effects of nifedipine and verapamil on body temperature in cats]. AB - Nifedipine and verapamil injected into the cerebral ventricles of unanaesthetized cats produced a longlasting rise in the body temperature. The hyperthermic effect of nifedipine and verapamil were not dose-dependent. The hyperthermic effect of verapamil was preceded by a shortlasting fall in the body temperature, which was not dose-dependent. Calcium antagonists, nifedipine and verapamil also produced mydriasis, tachypnoea, dyspnoea, ataxia, tremor and muscular weakness. These symptoms were inconsistent and of slight intensity. In agreement with the theory of ionic set point controlling the body temperature, the most probable explanation is that calcium antagonists, nifedipine and verapamil produced changes in the body temperature by acting on sodium and calcium fluxes in the posterior hypothalamus. PMID- 6241014 TI - [Promoting effect of portacaval anastomosis in experimental hepatic carcinogenesis]. AB - A promoting effect of portocaval anastomosis in a triphasic model of rat hepatocarcinogenesis is demonstrated since after initiation and selection premalignant lesions and hepatocellular carcinomas increase. This demonstrates that chronic administration of an exogenous compound is not the only way to promote cancer development. PMID- 6241015 TI - [Enzymatic and immunologic study of the role of the thyroid hormone in the formation of the internal mitochondrial membrane during postnatal development of the rat]. AB - Hypothyroidism induces an increase of liver D-beta-hydroxybutyrate dehydrogenase activity. Injection of thyroid hormone reverses the phenomena. The use of monospecific antibody raised against the purified enzyme indicates that there was not an increase of apoenzyme biosynthesis. The thyroid hormone negative control is due to a metabolism alteration of the membrane phospholipids which are directly involved in the apoenzyme activity. The highest difference is observed with 20 days old rats. Opposite effects were obtained on succinate cytochrome c reductase. PMID- 6241016 TI - [Variations in circulating levels of prolactin and growth hormone during physical exercise in man: influence of the intensity of the workout]. AB - In trained subjects, circulating PRL and GH increase significantly after a 20 minutes exercise on ergometer bicycle performed either at submaximal or maximal intensity. The magnitude of PRL response appeared to be similar for both kinds of exercise, but the increase in GH level is higher after maximal exercise than after submaximal one. PMID- 6241017 TI - [In vitro study of delta 6- and delta 5-desaturations of linoleic and dihomo gamma-linolenic acids during the development of arterial hypertension as a function of age in spontaneously hypertensive rats (SHR) as compared to normotensive rats (WKY)]. AB - delta 6- and delta 5-desaturations of linoleic [1(14)C] or dihomo-gamma-linolenic [2(14)C] acids are partially inhibited, in vitro, in liver microsomes of spontaneously hypertensive rats (SHR) comparatively to normotensive rats (WKY). The inhibition is more light when the animals are young and the blood hypertension not well established. These results are particularly important, for these desaturations are fundamental steps in the biosynthesis of prostaglandins precursors, prostaglandins and their original fatty acids being involved in blood pressure regulation. PMID- 6241018 TI - [Quantitative approach to the interactions of D-beta-hydroxybuturate dehydrogenase with phospholipids]. AB - Depending on the basis of the technique used, an estimation of 2 to 6 lecithin molecules are required for reactivation of purified D-beta-hydroxybutyrate apodehydrogenase (apoBDH). 60 to 70 mitochondrial phospholipid molecules are necessary for insertion of one BDH polypeptide chain where 16 molecules would be in direct interaction with the enzyme. Results show off the cofactor role of lecithin and also the requirement of an amphiphilic environment, essential for the enzyme function. PMID- 6241019 TI - [Placental fatty acids in the guinea pig during pregnancy]. AB - Prostaglandins are involved in different stages of reproduction. In respect to the placental metabolism of prostaglandins in the Guinea pig, we have studied the composition of Guinea pig placenta in free and total fatty acids. The arachidonic and dihomo-gamma-linolenic acids, precursors of prostaglandins of series 2 and 1, and the linoleic acid were quantified at different gestational ages using a gas chromatography capillary column technique. Only the linoleic acid shows a significant increase at the end of gestation. PMID- 6241020 TI - [Fatty acids in normal and pathological stratum corneum of humans]. AB - Fatty acids of triacylglycerols and free fatty acids have been studied in normal and hyperkeratotic human plantar stratum corneum. The results emphasize a decrease of long-chain fatty acids (greater than C18) in the hyperkeratotic tissues. Possible explanation for these findings are discussed in relation to the fatty acids metabolism in living epidermis. PMID- 6241021 TI - [Evolution of the regional blood deficit and energy metabolism after induction of transient cerebral ischemia by occlusion of the vertebral and carotid arteries in the rat]. AB - A transient brain ischemia of 10 min duration was produced in rats by electrocautery of the vertebral arteries and reversible occlusion of the carotid arteries. Ischemia reduced blood flow to 10-18% of the control values in forebrain structures (cortex, striatum, thalamus) and to 25-50% in the mesencephalon, cerebellum and brain stem. In these last structures, after 30 min of recirculation, the flow rates returned to normal values but a 20-35% reduction of blood flow was present in the forebrain structures, indicating that the development of the postischemic hypoperfusion was related to the severity of the preceding ischemia. After 30 min of recirculation, there was a near complete recovery of the high energy compounds but a residual metabolic dysfunction was evidenced by an increase in lactate/pyruvate ratio and an elevation of the glucose content, suggesting a depression of cerebral metabolism which may account for the brain hypoperfusion. PMID- 6241022 TI - [Inhibitory effects of Celiptium on thymidine kinase synthesis induced in the uterus by 17 beta-estradiol]. AB - Inhibitory effects of Celiptium on the thymidine kinase synthesis induced by oestradiol-17 beta in the rat uterus. In the rat uterus, the synthesis of thymidine kinase specifically induced by oestradiol-17 beta was inhibited by Celiptium. The synthesis was totally inhibited when the drug was administered before the oestrogen and partially when it was administered after. These facts suggested that Celiptium was competitive to the acceptor sites for oestradiol receptors and inhibited the expression of the thymidine kinase gene. PMID- 6241023 TI - [Immunoenzymatic detection of circulating antitumor antibodies in the rat: development of a quantitative technic and its use in rats bearing grafted colonic tumors]. AB - In order to study the humoral immune response of rats against a colonic tumor, we developed an immuno-enzymatic technique for quantitating specific anti-tumoral antibodies. This technique which uses a monolayer of intact cancer cells as antigen produces objective and reproducible results. Applied to eleven rats carrying grafted colon carcinomas, it allowed the characterization of three different types of evolution of the concentration of circulating antibodies. PMID- 6241024 TI - [Effect of temperature on diacetoxyscirpenol production and on sporulation in a liquid culture of Fusarium sambucinum]. AB - F. sambucinum grown for 14 days on peptone supplemented Czapek medium produced higher amount of diacetoxyscirpenol at + 15 degrees C than at + 25 degrees C or at temperature kept successively at + 15 degrees C (day) and + 5 degrees C (night). There was no correlation between the spores number and the toxin level, but toxin synthesis began only with sporification and then continued until the 14th day. PMID- 6241025 TI - [Determination of acetylcholine by inhibition of the specific binding of tritiated cis-methyldioxolane: application to the study of the effects of acetylcholine accumulation in a murine neuroblastoma culture]. AB - The radioreceptor assay for acetylcholine (ACh) is based on the ability of the ACh to compete with the specific binding of [3H] cis-methyldioxolane to muscarinic receptors of rat cerebral cortex membranes. The technique described was used to measure ACh levels in NS 20 cells treated with an organophosphorus compound. The down regulation of muscarinic acetylcholine receptors of neuroblastoma cells observed is probably related to ACh accumulation. PMID- 6241026 TI - [The repair of DNA damage induced in human lymphocytes by gamma rays and fast neurons]. AB - When Go human lymphocytes are exposed either to gamma-rays or to d(50)-Be neutrons and then immediately incubated in presence of cytosine arabinoside, the frequency of chromosomal aberrations which is normally observed after radiation exposure only is sharply increased. This enhancement of the aberrations, particularly the dicentrics, is, however, less marked when cytosine arabinoside is administered at longer intervals of time after irradiation. For gamma-rays, the treatment with cytosine arabinoside has no effect on the dicentrics yield when given 5 h after irradiation, indicating that the repair is completed within the 5 h after irradiation and that the lesions are not anymore available to produce exchange aberrations. For d(50)-Be neutrons, the time of repair takes approximately 5 h after a dose of 2.0 Gy, whereas it appears to be shorter (3 h) after a dose of 0.5 Gy. PMID- 6241027 TI - [Relative biological effectiveness of weak doses of neutrons for the production of dicentric chromosomes in human lymphocytes]. AB - The induction of dicentric chromosomes in G0 human lymphocytes has been used to determine the Relative Biological Effectiveness (RBE) of low doses of d(16 MeV) Be, d(33 MeV)-Be and d(50 MeV)-Be neutrons. Comparison of the dose-response curves obtained for neutrons with that found for gamma-rays indicates that RBE increases with decreasing neutron dose and with decreasing neutron energy, from d(50 Mev)-Be to d(16 MeV)-Be neutrons. The maximum RBE value at low doses has been evaluated by the linear components of the dose-response curves. It is equal to 14.0, 6.2 and 4.7 for the d(16 MeV)-Be, d(33 MeV)-Be and d(50 MeV)-Be neutrons respectively, when compared with the effects produced by the gamma-rays from 60 Co. PMID- 6241028 TI - [Serotonin receptors in the frontal cortex of the rat. Influence of supralethal irradiation]. AB - The density of the frontal cortex serotonin-2 receptors was determined after a supralethal irradiation (20 Gy) in Wistar rat. Using spiperone as ligand, we observed an important decrease in the density of serotonin-2 receptor and an increase in the dissociation constant receptor-ligand, 3 days after exposure. PMID- 6241029 TI - [Effect of age on the chromosomal radiosensitivity of bone marrow erythrocytes in the mouse]. AB - The frequency of cells with micronuclei has been determined in bone marrow polychromatic erythrocytes of 7 days, 12 weeks or 15 months old mice. This was also carried out in mice exposed to different doses of whole-body X-irradiation 30 hours before. Significantly more micronuclei were found in old control mice. The increase in micronuclei induced by irradiation, was not influenced by age. PMID- 6241030 TI - [Inhibition by methyl mercury chloride and mercuric chloride of the in vitro polymerization of microtubules]. AB - Mercury was tested at the same concentration but under two different forms, organic CH3HgCl and inorganic HgCl2, in order to compare its relative inhibitory effect on in vitro microtubules polymerization. Induced by GTP and glycerol 8 M, tubulin polymerization was completely inhibited by HgCl2 10(-3) M while a 75.8% inhibition was measured for CH3HgCl2 10(-3) M. PMID- 6241031 TI - [Changes in the global electromyogram during static exercise; effect of age]. AB - In normal man, the EMG changes in forearm muscles holding a tension of 30% maximal voluntary strength for 5 minutes are: (1) an increase of integrated EMG, (2) a slight decrease of the median frequency of the EMG power spectrum. These changes are largely reduced with age. PMID- 6241032 TI - [Incorporation of androgens at the time of cell differentiation of the prostatic epithelium in the rat]. AB - The appearance of androgen binding sites and acid phosphatase and esterase activities in the rat prostatic epithelium during the normal development was studied by means of steroid autoradiography and enzyme histochemistry. The incorporation of androgen into the prostatic epithelium began immediately before the lumen formation in the prostatic buds and the onset of their functional differentiation. PMID- 6241033 TI - [Organotypic culture of the genital tubercle of the fetal rat: induction of the os penis by testosterone]. AB - Genital tubercles of male and female fetal rats were cultured in vitro with or without testosterone. The mesenchyme of the genital tubercles of both sexes can be differentiated into two cartilages corresponding to the two segments of the os penis only in the presence of testosterone. PMID- 6241034 TI - [Analgesic anesthesia in children less than 10 years old (combination of dextromoramide and a relaxant)]. PMID- 6241035 TI - Mucin synthesis. The action of pig gastric mucosal UDP-GlcNAc:Gal beta 1 3(R1)GalNAc-R2 (GlcNAc to Gal) beta 3-N-acetylglucosaminyltransferase on high molecular weight substrates. AB - Membrane preparations from pig gastric mucosa were shown to transfer [14C]GlcNAc from UDP-[14C]GlcNAc to blood group A-negative porcine submaxillary mucin previously subjected to mild acid hydrolysis to remove terminal sialyl and fucosyl residues. O-Glycosyl oligosaccharides were removed from enzyme product by alkaline borohydride treatment and, after purification, were subjected to high resolution proton nuclear magnetic resonance spectroscopy and methylation analysis. Two trisaccharide products were detected: [14C]GlcNAc beta 1-3Gal beta 1-3GalNAcOH and Gal beta 1-3[( 14C]GlcNAc beta 1-6)GalNAcOH. We have previously reported the in vitro synthesis of the latter compound, a branched trisaccharide, by UDP-GlcNAc:Gal beta 1-3GalNAc-R (GlcNAc to GalNAc) beta 6-N acetylglucosaminyltransferase from canine submaxillary glands. However, this is the first report of the in vitro synthesis of the linear trisaccharide GlcNAc beta 1-3Gal beta 1-3GalNAc. Pig gastric mucosal beta 3-N acetylglucosaminyltransferase catalyzed the formation of this trisaccharide by incorporation of GlcNAc into the terminal Gal of Gal beta 1-3GalNAc-alpha-R when R was a polypeptide from either mucin or antifreeze glycoprotein, but not when R was o-nitrophenyl. We have previously reported the in vitro synthesis by pig gastric mucosa of the tetrasaccharide GlcNAc beta 1-3Gal beta 1-3(GlcNAc beta 1 6)GalNAc-alpha-R when R was o-nitrophenyl or benzyl. We show in this report that pig gastric mucosa can synthesize this tetrasaccharide in vitro when R is a polypeptide from either porcine submaxillary mucin or antifreeze glycoprotein. Pig gastric mucosa therefore contains a beta 6-N-acetylglucosaminyltransferase capable of converting Gal beta 1-3GalNAc-alpha-R to Gal beta 1-3(GlcNAc beta 1 6)GalNAc-alpha-R and one or more beta 3-N-acetylglucosaminyltransferases which can add GlcNAc in beta 1-3 linkage to a terminal Gal residue to form either GlcNAc beta 1-3Gal beta 1-3GalNAc-alpha-R or GlcNAc beta 1-3Gal beta 1-3(GlcNAc beta 1-6)GalNAc-alpha-R where R is the polypeptide backbone of either mucin or antifreeze glycoprotein. PMID- 6241036 TI - The ATPase complex of Escherichia coli. AB - The ATPase (ATP synthase) complex of Escherichia coli is composed of an extrinsic membrane protein (ECF1), which contains the active site for ATP formation and hydrolysis, and is attached to ECF0, a transmembrane protein through which protons move to or from the active site on ECF1. ECF1 is composed of five subunits (alpha-epsilon) with a stoichiometry of alpha 3 beta 3 gamma delta epsilon. The stoichiometry of the three subunits (a-c) of ECF0 is probably a1b2c10-15. In addition to 3 mol tightly bound adenine nucleotide/mol ECF1, three other "exchangeable" nucleotide binding sites can be detected. These sites are still present in the alpha and beta subunit defective ECF1 of uncA401 and uncD412 mutants, although some changes in the tightness of binding are evident. The active sites of ECF1 require normal alpha and beta subunits and may be present at alpha beta subunit interfaces. Hydrolysis of ATP requires cooperative interactions between alpha and beta subunits. At low concentrations of ATP, in the absence of added divalent cations, hydrolysis of this substrate can occur at a single site without release of the product. This is consistent with alternating or sequential site mechanisms for ATP hydrolysis or synthesis. Predictions of secondary and tertiary structures from the known primary amino acid sequences of polypeptides a, b, and c have led to the following conclusions. Polypeptide a forms six or seven transmembrane alpha helices. The amino-terminal sequence of polypeptide b spans the membrane, but most of the protein is exposed on the cytoplasmic surface of the membrane where it can be cleaved by proteases in vitro.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 6241037 TI - Effect of ozone on prophage induction in different strains of Escherichia coli K 12 lysogenic for lambda. AB - Ozone was tested for its effect upon induction of lambda prophage in two different strains of Escherichia coli K-12. Based on the induction index and when compared to ultraviolet light, ozone appeared to be a weak, if any at all, inducer of the lytic cycle in E. coli. This is in agreement with other studies which have suggested that this agent is a weak inducer of the SOS functions. PMID- 6241038 TI - Aminoglutethimide in the treatment of advanced breast cancer. PMID- 6241039 TI - Opsin-immunoreactive outer segments of photoreceptors in the eye and in the lumen of the optic nerve of the hagfish, Myxine glutinosa. AB - Opsin-immunoreactive sites in the eye and optic nerve of the hagfish, Myxine glutinosa, were studied by use of light-microscopic pre- and postembedding peroxidase-antiperoxidase or avidin-biotin-peroxidase techniques, and the immuno electron-microscopic protein A-gold method. At the light-microscopic level, a strong opsin immunoreaction was obtained on the outer segments of the photoreceptor cells with sheep and rat antibodies against bovine (rhod)opsin. These outer segments were located in the marginal photoreceptor space and in follicles of the retina, as well as in the tubular lumen of the optic nerve. Ultrastructurally, two classes of outer segments can be distinguished; most of them exhibited a strong antiopsin reaction, while certain elements lacked immunoreactivity with the antisera employed. The protein A-gold particles marked opsin-immunoreactive sites on the photoreceptor membranes. The presence of opsin immunoreactive material in the retina and optic nerve of the hagfish strengthens the view that this primitive eye lacking a cornea, lens and vitreous body is engaged in light perception. The morphological similarity between the eye and pineal tissue is discussed in connection with the absence of a pineal organ in this species. PMID- 6241040 TI - [Orthotopic cardiac allotransplantation in the neonatal goat]. PMID- 6241041 TI - [Studies on thymic peptide factors. III. Isolation, purification, biochemical property and E-rosette activity in vitro of porcine thymic factors]. PMID- 6241042 TI - [Effects of aclacinomycin B on biological macromolecular contents and synthesis of L1210 cells]. PMID- 6241043 TI - [Diagnosis of autoimmune thyroiditis]. PMID- 6241044 TI - [Correlative cardioelectrical signal studies based on time and frequency domains- an analysis of ECG waves]. PMID- 6241045 TI - [Auditory myogenic response in normal subjects]. PMID- 6241046 TI - [Significance of classification of acute and chronic types of aplastic anemia (retrospective analysis)]. PMID- 6241047 TI - [Effects of epidural anesthesia in patients with different pulmonary reserves]. PMID- 6241048 TI - [Characterization of Plasmodium yoelii antigens by monoclonal antibodies. II. In vivo assay of the protective effect of monoclonal antibodies]. PMID- 6241049 TI - [Neurohumoral regulation of renin-angiotensin system. II. Effect of electro stimulation of central gray and intraventricular injection of angiotensin II on the plasma cyclic nucleotide content in cats]. PMID- 6241050 TI - [Effect of excitation of the peripheral ends of the abdominal vagus on the release of spleen catecholamines in cats]. PMID- 6241051 TI - [Mutagenicity of bis(2,3-epoxy-cyclopentyl) ether]. PMID- 6241052 TI - [Studies on viral immunotherapy of ascitic tumors in mice. I. Results of treatment with virus on Ehrlich and S180 ascitic tumor cells]. PMID- 6241053 TI - [Effects of pyquiton on pulmonary S. japonicum egg granulomas in sensitized mice]. PMID- 6241054 TI - [Brain herniation (temporal lobe) into the mastoid cavity]. PMID- 6241055 TI - [Inhibitory effect of N-4-aminosulphonylphenyl-retinamide and other 2 new retinoids on malignant change of forestomach dysplasia in mice]. PMID- 6241056 TI - [Isolation of normal human serum IgG subclasses]. PMID- 6241057 TI - [Detecting HBeAg and anti-HBe by ELISA]. PMID- 6241058 TI - [Comparison studies on levels of CIC, complement C and its breakdown product C3c in chronic bronchitis and systemic lupus erythematosis]. PMID- 6241059 TI - [Purification and characterization of DNA polymerase alpha from Ehrlich ascites cells]. PMID- 6241060 TI - [Preparation and characterization of mouse monoclonal antibodies against human C3]. PMID- 6241061 TI - [Cloning of Adr HBV genome and its surface antigen gene]. PMID- 6241062 TI - [Myotonic muscular dystrophy (clinical and electromyographic studies of 21 cases)]. PMID- 6241063 TI - [Muscle biopsy in polymyositis; report of 20 cases]. PMID- 6241064 TI - [Normal pressure hydrocephalus--report of 4 cases]. PMID- 6241065 TI - [Surgical management of secondary deformities of cleft lip and nose]. PMID- 6241066 TI - [A comparative study on rapid and slow loading of gossypol in the treatment of gynecological diseases]. PMID- 6241067 TI - [Clinical phase II trial of a new antineoplastic drug--glyciphosphoramide]. PMID- 6241068 TI - [Echocardiographic evaluation of cardiac function in acute myocardial infarction patients and its recent prognosis]. PMID- 6241069 TI - [Subclinical cerebral cysticercosis and Biltricide (praziquantel)]. PMID- 6241070 TI - [Isolation and preliminary analysis of surface membrane antigen from adult worm of Schistosoma japonicum]. PMID- 6241071 TI - [Preparation of CT-HRP with domestic and foreign materials and comparison of their labeling effect]. PMID- 6241073 TI - [Normal pulmonary artery pressure in China]. PMID- 6241072 TI - [Synthesis of the 14C labelled anticancer agent: N,N-bis(beta-chloroethyl)-N',N" di(carboethoxy-[14C] methyl)-phosphorotriamide]. PMID- 6241075 TI - [Synthesis of DL-[15N] proline]. PMID- 6241074 TI - [Primary structural analysis of a case with Hb Queens]. PMID- 6241076 TI - [Effect of indirubin on SCE frequencies of BM cells in chronic myeloid leukemia]. PMID- 6241077 TI - [Determination of heritable reciprocal translocation]. PMID- 6241078 TI - [State of hepatitis B virus DNA and stability of expression of HBsAg in transformed pC-3-1 cells]. PMID- 6241079 TI - [Studies on E-receptors II. Purification of E-receptors with affinity chromatography]. PMID- 6241081 TI - [Detection of antibody to type B influenza virus in pig populations in China]. PMID- 6241080 TI - [Studies on endotoxin of Leptospira: I. Extraction of lipopolysaccharides from Leptospira interrogans serovar Lai and analysis of their chemical and biological properties]. PMID- 6241082 TI - [A study of the antitumor action of glyciphosphoramide]. PMID- 6241083 TI - [Radioprotective mechanism of a preparation extracted from TFB. I. Effects on the hemopoietic system in mice]. PMID- 6241084 TI - [Effect of a combined use of propranolol and nifedipine on experimental myocardial infarct size]. PMID- 6241085 TI - [Identification of monoclonal antibodies against human IgA]. PMID- 6241086 TI - [Detection of mouse-specific IgG to TKM with ELISA]. PMID- 6241087 TI - [Studies on growth conditions of EHF virus in primary rat lung cell culture]. PMID- 6241088 TI - [Visual, auditory and somatosensory pathway involvement in Charcot-Marie-Tooth disease]. PMID- 6241089 TI - [Preliminary observation on methyl-prednisolone in the treatment of SLE]. PMID- 6241090 TI - [Preliminary observation of the effect of thymosin on myasthenia gravis]. PMID- 6241091 TI - [Intracranial hemorrhage following open heart surgery (report of 4 cases)]. PMID- 6241092 TI - [Secretin test and its applications]. PMID- 6241093 TI - [Radioimmunoassay of T3, T4, T3u, FTI and TSH in diagnosis of thyroid diseases]. PMID- 6241094 TI - [Effects of variation in dietary sodium intake on plasma catecholamines in normal subjects]. PMID- 6241095 TI - [Extraction of the core and matrix proteins and preparation of antisera from type A influenza virus]. PMID- 6241096 TI - [Effects of endotoxin on activity of erythrocyte acetylcholinesterase]. PMID- 6241097 TI - [Histopathological and histochemical studies on toxic effect of brodifacoum in mouse liver]. PMID- 6241098 TI - [Some characteristics of the study of Chinese traditional medicine]. PMID- 6241099 TI - [Seasons for collecting Chinese drugs]. PMID- 6241100 TI - [Taiwan Province to reprint "The appearance of metals, stones, insect, herbs and woods", a picture scroll painted in the late Ming dynasty]. PMID- 6241101 TI - [Botanical origin of the Chinese drug lu-xian-cao]. PMID- 6241103 TI - [The determination of the microscopic constant and physicochemical identification of the leaves of a species of da-qing]. PMID- 6241102 TI - [The medicinal portion of leaves of the purple perilla available on the market and the quantitative determination of its volatile oil content]. PMID- 6241104 TI - [Preliminary study of cotton seed processing]. PMID- 6241105 TI - [Mildew of tortoise-plastron gelatin and 3 other Chinese medicinal herbs]. PMID- 6241106 TI - [Advances in the past decade and prospects of quality standards of Chinese traditional medicinal preparations]. PMID- 6241107 TI - [Chemical constituents of flower-buds of Panax ginseng--isolation and identification of ginsenoside-Rb3 and ginsenoside-Rc]. PMID- 6241108 TI - [Chemical constituents of hairy young horn of Capreolus capreolus--isolation and identification of fat-soluble constituents]. PMID- 6241109 TI - [GC/MS analysis of volatile oils from Chinese Asarum species. II. Asarum sieboldii form. seoulense, A. forbesii, A. inflatum, A. magnificum var. dinghugense and A. caudigerum var. cardiophyllum]. PMID- 6241110 TI - [The scolicidal action of bing-lang and other Chinese medicines against Echinococcus granulosus protoscoleces for screening in vitro]. PMID- 6241111 TI - [Effect of several Chinese drugs on platelet aggregation in the rabbit]. PMID- 6241112 TI - [Effect of soyasaponin on hyperlipemia of rabbits induced by Adeps suillus and on the endurance to anoxia in mice under normal pressure]. PMID- 6241113 TI - [A course in English on Chinese materia medica. (15)Li Shi-Zhen--a great physician and herbalist]. PMID- 6241114 TI - [Spontaneous hemoperitoneum]. AB - The authors report their experience of 11 cases of hemoperitoneum due to hemorrhagic endoabdominal neoformation, diagnosed through laparoscopy, and the diagnosis of which was confirmed by the biopsy under the sight. They describe the casuistry observed: 4 hepatic neoplasms (11,9%); 4 ovary neoplasmus (12,1%); 1 neuroblastoma (10%); 2 ovary endometriosic cysts (16,6%). They, at last, emphasize the usefulness of laparoscopy as an investigating mean offering a sure diagnostical reliability. PMID- 6241115 TI - Follow-up after successful transluminal angioplasty. Report of the initial Cleveland Clinic experience. PMID- 6241116 TI - [Systemic disorders of patients in dental practice. Significance of the problem and effect on treatment planning]. PMID- 6241117 TI - Plasmapheresis therapy in immunologically mediated rheumatic and renal diseases. PMID- 6241118 TI - Pathophysiology of pregnancy-induced hypertension. PMID- 6241119 TI - Chronic anovulation. PMID- 6241120 TI - Formation and function of the classical and alternative pathways of complement. PMID- 6241121 TI - Relationships among the complement, kinin, coagulation and fibrinolytic systems in the inflammatory reaction. PMID- 6241122 TI - Changes in the distribution of laminin, fibronectin, type IV collagen and heparan sulfate proteoglycan during colony formation by chick retinal pigment epithelial cells in vitro. AB - Retinal pigment epithelial cells isolated by non-enzymatic means from 8 day old chick embryos were grown as explants on glass coverslips in culture. Retinal pigment epithelial cells grown in this way form colonies in which three zones, each containing cells with distinctly different morphology, pigmentation, adhesion pattern and cytoskeletal organization, can be distinguished (Turksen et al., 1983). Using specific antisera against laminin, fibronectin, type IV collagen, and heparan sulfate proteoglycan, we have found differences in the distribution of these basement membrane components in the three zones of each colony. When cells were stained with laminin, type IV collagen and fibronectin antibodies, extensive filamentous arrays were observed on the substratum side of the cells. In contrast to type IV collagen which was deposited to a similar degree in all three zones of each colony, laminin and fibronectin were most prominent in the central zone in which the packed cuboidal differentiated cells are located. In contrast to the other components, the heparan sulfate proteoglycan appeared to be associated primarily with the cell surface. Our results support the general view that basement membrane components could influence cell shape through an effect on the cytoskeleton, and play a role in the maintenance and expression of the differentiated state. Thus retinal pigment epithelial cells might provide a very useful model system for studying the interactions between the cytoskeleton and extracellular matrices and the biosynthesis of the BM components in epithelial cells. PMID- 6241123 TI - In vivo and in vitro testing of gloves for protection against UV-curable acrylate resin systems. AB - In vitro data demonstrated that the permeation of a UV-curable urethane acrylate resin system through glove materials was greatest for latex and neoprene gloves and less for two nitrile gloves. Permeation in vitro for the resin system took longer than 480 min. Individual components of the resin permeated faster when tested separately than when in the formulated system. In vivo 48-h patch test data suggested that neither nitrile glove would be adequate for worker protection, but the in vivo test exaggerated the duration of contact between resin, glove, and skin. Both nitrile gloves provide adequate protection under use conditions, provided the gloves were not re-used within 8 h. PMID- 6241125 TI - Buphenine sensitivity. PMID- 6241124 TI - Occupational dermatoses in Singapore. AB - A study of occupational dermatoses is described. 97% of 389 cases were contact dermatitis, of which 66.3% were irritant and 33.7% allergic, in both male and female workers. Cutting oils, solvents and flux from the engineering and electronic industries were the commonest irritants, and chromate from cement in the construction industry was the commonest allergen. The other occupational allergens were rubber chemicals and epoxy resin. The construction industry was the largest source of occupational dermatoses cases seen; possible preventive measures are discussed. PMID- 6241126 TI - Benzoyl peroxide contact allergy in leg ulcer patients. PMID- 6241127 TI - Occupational contrast media dermatitis: meglumine diatrizoate. PMID- 6241128 TI - Eczematous drug reaction from phenobarbitone. PMID- 6241129 TI - Occupational dermatitis in a butcher. PMID- 6241130 TI - Occupational dermatitis caused by snackbar meat products. PMID- 6241131 TI - Contact allergy to benzoxonium chloride (Bradophen). PMID- 6241132 TI - Determination of contribution of arteriovenous fistula to total cardiac output by Doppler computer. PMID- 6241133 TI - Echocardiographic aspects of cardiac hypertrophy and dilatation in normo- and hypertensive hemodialyzed patients. PMID- 6241134 TI - Left ventricular morphology and function in mild to moderate essential hypertension. AB - 150 males with mild to moderate essential hypertension [EH] were examined echocardiographically and the findings in the left ventricle [LV] were compared with those in 20 normotensive men. Increased LV wall thickness and LV mass was found in 81% and 67% of hypertensives respectively in contrast with a complete absence of LV hypertrophy in normotensives. The former showed also a tendency to the concentric type hypertrophy, which can be considered a characteristic feature of the 2nd stage [WHO] EH. There was an almost uniform incidence of asymmetric septal hypertrophy in the two groups [12 vs. 10%]. Decreased LV end-systolic wall stress in EH was a sign of compensatory myocardial hypertrophy without LV dilatation. The hypertensives exhibited a normal or slightly elevated systolic LV function. On the other hand, some indirect indices of LV properties [peak rate of LV relaxation and left atrial dimension] were indicative of diastolic function impairment. A slight but significant correlation between the degree of LV hypertrophy and systemic blood pressure at rest was found in a part of hypertensive patients. The study indicates that mild to moderate EH leads to some changes in LV morphology and function, which can be easily recognized by echocardiography. PMID- 6241135 TI - Distribution of T-lymphocyte subsets in patients with vascular diseases. AB - The distribution of T-lymphocyte subsets was studied in patients with myocardial infarction, peripheral arterial disease and thrombophlebitis. The percentage of SRBC-rosette forming active - E[A] and total - E[T] lymphocytes in patients and healthy controls was not different. A significant increase in the percentage and number of theophylline-resistant - E[Thr] and T[M] - helper cells was found in patients with myocardial infarction or with thrombophlebitis, and a moderate elevation was observed in patients with peripheral arterial disease. No difference between patients and controls could be shown in the percentage and number of theophylline-sensitive E[Ths] and T[G] - suppressor cells. The imbalance of T-lymphocyte subsets is thought to be the consequence of sensitization against vascular tissues during vascular diseases. PMID- 6241136 TI - Opsin-induced experimental autoimmune retinitis in rats. AB - Experimental autoimmune retinitis has been induced in Lewis rats by injection of opsin in mycobacterial adjuvant and Hemophilus pertussis adjuvant. Clinical, histopathological and immunological parameters of the disease are reported. Two types of opsin were prepared from purified bovine retina outer segments, one type in Triton X-100 and the other in lithium dodecyl sulfate. Both preparations were free from S-antigen. Dodecyl sulfate-denaturated-opsin displayed lower antigenicity and pathogenicity than Triton-opsin. Triton-opsin (250 micrograms) induced moderate to severe non-granulomatous uveitis (predominantly retinitis) in 70% of the Lewis rats at the end of the second week after injection. The photoreceptor cell layer was destructed within a few days. This group displayed high responses to opsin in the lymphocyte transformation test. In view of observed histological features, the possible early involvement of vasoactive factors is discussed. Low opsin doses (50 or 100 micrograms) seldomly induced severe retinitis, while the incidence of mild pathology was low. Lewis rats appeared to be more susceptible for the development of experimental autoimmune retinitis than Wistar rats. PMID- 6241137 TI - Morphology of haemorrhagic shock, systemic immunocomplex reaction and systemic anaphylactic reaction. A comparative study. AB - Diagnosis and pharmacological control of shock represent the problems of everyday public health practice. Our experimental approach using three different shock models contributes to further elucidation of the pathogenesis of haemorrhagic shock as well as shock developing during systemic anaphylactic reaction (SAR) and systemic immunocomplex reaction (SIR). It could help to explain why adequate diagnosis and application of mostly proved and commonly used therapeutic procedures may fail under some conditions. For the future, based on our and other experimental data obtained in particular by techniques of electron microscopy, it will be perhaps possible to consider some new interpretations of findings occurring in humans who died in shock reactions and in those with a suspicion of clinically diagnosed shock respectively. PMID- 6241138 TI - [Homology of the amino acid sequences between histones H3 and H4 and regulatory proteins]. PMID- 6241139 TI - [Genes of DNA methylase EcoK: their cloning and expression]. PMID- 6241140 TI - [Diseases caused by atypical mycobacterial]. AB - Infections having atypical mycobacteria are occurring more frequently for 2 main reasons. First there are the disturbances of the immunity system, whether due to the acquired immune deficiency syndrome (AIDS) or the result of therapeutic measures taken against malignant processes, other diseases or after organ transplantation. Second, travel and free-time activities increase the risk of an infection. In many cases such infections become localized on the skin, but can also develop changes in the lungs, depending on the patient's occupation. For this reason we provide a review of the new literature on the microbiology of mycobacteria as well as on the symptoms of diseases of the skin and other organs which are caused by atypical mycobacteria, such as swimming pool granuloma or Buruli ulcer. PMID- 6241141 TI - Primary and secondary sites of occupational contact dermatitis. AB - Patterns of distribution of allergic contact dermatitis follow a certain order in time. The disease starts at a given site, most often as a unilateral acrodermatitis and, should it become chronic, spreads locally. The subsequent pattern of distribution varies depending on the primary site and the type- occupational or otherwise--of the disease. In this study data collected two decades ago are confronted with the more recent ones relating to 1055 cases of occupational allergic contact dermatitis. Examination of this material brought to light no essential difference between the older and more recent patterns of distribution of secondary sites. The incidence, however, of certain multiple localizations and of the primary or secondary involvement of the face has diminished. PMID- 6241142 TI - [Allergic contact eczema caused by isothiazolin-3-one derivatives]. AB - Observations concerning contact dermatitis to derivatives of isothiazolin-3-one are reported. A systematic review of the literature of previously published cases is reported. A verified contact dermatitis to benzisothiazolin-3-one of a laborer in a rubber factory is discussed. Another case of occupational dermatitis concerns an allergy to a commercial product, containing 2-n-octyl-4-isothiazolin 3-one as a preservative and utilized by shoe factory workers. Additionally, cases of an allergy to cosmetic preparations, containing a mixture of 5-chloro-2-methyl 4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one, are elaborated. PMID- 6241143 TI - Hyperkeratosis palmoplantaris with periodontosis. "Papillon-LeFevre syndrome". Report of three cases in the same family. PMID- 6241144 TI - [Method of assessing the functional activity of tumor-associated suppressor cells]. AB - A relatively simple and easily reproducible method is presented for testing the activity of tumour-associated suppressor cells in the syngeneic system. It includes adoptive transfer and radioactive assay of the inhibition degree of the specific proliferative response to tumour cells of syngeneic recipients. PMID- 6241145 TI - [Surface phenotype and suppressor function of the blood lymphocytes in multiple myeloma]. AB - Surface phenotype of peripheral blood lymphocytes was studied in 18 patients with myeloma by combined rosette-forming and immunofluorescent methods. A high content of B lymphocytes with the identical type of immunoglobulin, and a decreased level of T lymphocytes were revealed. The increased activity of spontaneous and Con A induced suppressor activity and cytochemical changes of some intracellular hydrolytic enzymes were found in lymphocytes of patients with myeloma. PMID- 6241146 TI - Aerobic capacity of severely disabled Indians. PMID- 6241147 TI - Cellular distribution of three mammalian Ca2+-binding proteins related to Torpedo calelectrin. AB - Addition of Ca2+ to post-microsomal fractions of bovine adrenal or liver produced a sedimentable complex of membrane vesicles and cytoplasmic proteins. Proteins with apparent mol. wts. 70 000, 36 000 and 32 500 were solubilized from this complex by Ca2+ chelation. The 36 000 mol. wt. protein (p36) was immunoprecipitated by an antiserum specific for pp36, a major substrate for Rous sarcoma virus src-gene tyrosine kinase. This protein was present in many mesenchymal cells and associated with membrane cytoskeleton of bovine fibroblasts in a Ca2+-dependent manner. The 70 000 and 32 500 mol. wt. proteins were widely distributed in established cell lines, but were not clearly associated with cell organelles in tissue sections, nor retained in cytoskeleton preparations. On immunoblots p36 reacted strongly with antibodies produced against the electric fish protein Torpedo calelectrin and the similar Ca2+-binding properties and subunit mol. wts. of these proteins suggests that they might be functionally related. Since Torpedo calelectrin, p70, p36 and p32.5 were bound by lipid vesicles or microsomal membranes at micromolar free Ca2+ concentrations, regulated association with intrinsic membrane components may be involved in the functions of these widespread proteins. PMID- 6241148 TI - Kinetics of internalisation and degradation of surface-bound interferon in human lymphoblastoid cells. AB - The binding of iodinated human interferon-alpha 2 (IFN-alpha 2) was studied on the human T cell line, Molt 4. After its initial binding to cells, the IFN is transferred to a trypsin-resistant compartment before appearing in the medium as TCA-soluble material, while the total cell-associated IFN declines to one-third of its maximum value after 3 h incubation. The Na+/H+ ionophore monensin did not prevent intracellular accumulation of IFN but did completely inhibit its breakdown. We interpret our results as evidence for receptor-mediated internalisation of IFN followed by intracellular breakdown. PMID- 6241149 TI - All eight unassigned reading frames of mouse mitochondrial DNA are expressed. AB - Animal mitochondrial DNA contains genes for 13 potential polypeptides of significant size. Five of these genes have been assigned to distinct proteins and eight remained unassigned reading frames (URFs). Short peptides corresponding to URF protein sequences were synthesized chemically. Antibodies raised to these synthetic peptides were used to establish the existence of all eight URF proteins in mouse tissues and cells by the complementary techniques of immunoperoxidase staining, protein blotting and immunoprecipitation. Immunoperoxidase staining of thin-sectioned, freeze-substituted tissue may prove generally useful for the identification of gene products for which no formal genetic data exist. Furthermore, the ability to determine the cellular and tissue distribution of such proteins may provide the first insight into their function. PMID- 6241150 TI - Different Z DNA forming sequences are revealed in phi X174 RFI by high resolution darkfield immuno-electron microscopy. AB - The specific interaction between left-handed Z DNA sequences in negatively supercoiled bacteriophage phi X174 replicative form I (RFI) DNA and anti-Z DNA immunoglobulin G (IgG) was investigated by high resolution darkfield immuno electron microscopy. DNA-antibody complexes were formed and maintained under optimal binding conditions, purified by column chromatography, and visualized after uranyl acetate staining without using aldehyde fixation, shadowing, or second antibody. Bivalent anti-Z DNA IgGs bound to RFI molecules, thus forming intramolecular bridges. They could also oligomerize separate molecules by intermolecular linking of Z DNA sequences. At relatively low ionic strength and low temperature, high affinity anti-Z IgG was retained at certain loci even after restriction endonuclease cleavage of the DNA. In these cleaved molecules some superhelices could be visualized in the loops generated by the bivalent IgG. To our knowledge this is the first example of polypeptide stabilization of local superhelical strain in a cut molecule. Z DNA sequences in phi X174 RFI DNA were mapped. Alternating tracts of purines and pyrimidines starting at nucleotides 763, 1027, 1714, 2146, 2363, 3504, 4161, 4911 and 5345 occur within the nine different anti-Z IgG binding sites which were expressed with varying frequencies (53-3%) on the molecules. Usually, a limited number of sites (generally less than or equal to 2) exists on any one molecule. The formation of multiple Z sites (at the extracted superhelix density) in a given molecule is probably non-cooperative due to relaxation of torsional stress by the B----Z transition. Z sites occur in several different genes, including regions where transcription is attenuated and, in one case, in front of a promoter of transcription. PMID- 6241151 TI - Pitfalls in the diagnosis of neuroblastoma by 99mTc-MDP scintigraphy: a case report. AB - A routine bone scan was performed on an infant presenting with abdominal mass. Initially, the stasis of activity in the right ureter, which was compressed by a large abdominal meningocoele, was mistaken for activity in a neuroblastoma. A subsequent kidney scintigram led to the correct interpretation. The misinterpretation of abdominal 99mTc-MDP accumulation can be prevented by the correlation of bone and kidney scintigrams. In this way, the correct site of the radiopharmaceutical concentration can be assessed, and the damage caused by any kind of abdominal mass to the compressed urinary tract and kidney can be assessed. PMID- 6241152 TI - Controversy in Medicine Debate: the defect in rheumatoid arthritis is inherent to the lymphocyte. PMID- 6241153 TI - Plasma dehydroepiandrosterone, dehydroepiandrosterone sulphate and androsterone sulphate levels and their interaction with plasma proteins in rheumatoid arthritis. AB - Female patients with rheumatoid arthritis (RA) in Steinbrocker's II and III rating scale have been examined. They were without steroid treatment at least six months before observation. Plasma protein picture showed hypoalbuminaemia and hyperglobulinaemia. There was no difference relative to controls either in the total (free + protein bound) plasma dehydroepiandrosterone (D) level, or in its distribution with plasma proteins. In the age group of 18 to 45 years, a statistically significant decrease have been observed in the total plasma dehydroepiandrosterone sulphate (DS) level without any change in its distribution in protein binding. Furthermore, low androsterone sulphate (AS) levels were found irrespective of the age of patients. The results gave further information on the pathomechanism resulting in an abnormal androgen hormone pattern of blood and a low metabolite excretion, observed previously in patients with RA:. PMID- 6241154 TI - [Epithelial attachment in implantology (biological tolerance of the materials]. PMID- 6241155 TI - [Experimental evaluation of composite material restorations, using 2 different types of bonding resins]. PMID- 6241156 TI - T cell subsets and macrophages in lichen planus. In situ identification using monoclonal antibodies and histochemical techniques. AB - Skin lesions from 6 patients with lichen planus were studied for the presence of T cells and T cell subsets using monoclonal antibodies and indirect immunoperoxidase technique. Small numbers of Leu-2a-reactive suppressor-cytotoxic cells were present early in the basal cell layer in 2 patients with recent lesions. The analysis of T cell subsets revealed the predominance of anti-pan-T cell (Leu-1)- and Leu-3a-reactive helper-inducer cells in 4 patients with older active lichen planus lesions. Significant numbers of suppressor-cytotoxic cells were observed in the papillary dermis and within the epidermis associated with hydropic degeneration of the basal cell layer. Activated T lymphocytes with focal acid phosphatase activity, together with activated histiocytes-macrophages with strong diffuse activity of acid phosphatase and non-specific esterase, were identified in the dermis and within the epidermis. These findings suggest that a cytotoxic immune process directed against the basal cell layer of the epidermis is the dominant pathogenic event in lichen planus. PMID- 6241157 TI - Characterization of cellular infiltrates in skin lesions of atopic eczema by means of monoclonal antibodies. AB - Frozen skin biopsies from 3 acute and 3 chronic lesions of atopic dermatitis were examined by means of various ortho-monoclonal antibodies (OKT3, 4] not equal to-- -4, OKT6, OKT8; OKIa and OKM1) in an indirect immunofluorescence technique. The results show that both T helper (T4) and T suppressor cytotoxic (T8) lymphocytes are present in the inflammatory infiltration which predominantly contained Ia mononuclear cells. Despite the absence of double staining procedure, the observations suggest that T4 cells predominate over T8 cells in the acute lesions whereas the reverse tendency is noted in the chronic lesions. T8 cells are found mainly in the superficial dermis or even in the epidermis; by contrast, T4 cells tend to be more deeply located in the dermis. The lesions are characterized by a dramatic increase in the number of Langerhans cells (OKT6, OKIa+) that are found not only in the epidermis but also in the dermis. PMID- 6241158 TI - Non-traumatic removal of the nail and simultaneous treatment of onychomycosis. AB - There are no doubt a great many therapeutic recommendations for the treatment of onychomycoses. However, as so often, it soon becomes evident that the number of therapeutic regimens appear to indicate a wide range of therapeutic possibilities, but the rates of cure actually achieved are in complete contrast to these. The prerequisite for treatment is the identification of the causative fungi on direct microscopic examination and in culture to avoid the use of antifungals in changes of the nails other than onychomycoses. Another very important prerequisite for systematic treatment is the removal of as much fungus infected nail material as possible, or else bioavailability at the site of infection cannot, or only hardly, be guaranteed. In our investigations into the treatment of onychomycosis we studied the use of bifonazole (1%)-urea ointment and the therapeutic possibilities in connection with its application. PMID- 6241159 TI - Treatment of sebopsoriasis. A clinical trial--an etiological approach. AB - 1% Bifonazole cream and gel were used for the local therapy of sebopsoriasis and psoriasis in a pilot study with 20 patients. 3 of the 9 patients with psoriasis and 9 of the 11 patients with sebopsoriasis had improved markedly. The mechanisms of the effectiveness of this therapy will be discussed together with the results of some provocation tests with bacterial antigens. PMID- 6241160 TI - Bifonazole--a synopsis of clinical trials worldwide. Status and outlook. AB - A synopsis is given on the results of 97 clinical trials of efficacy and tolerability involving a total of 3,443 patients in more than 20 countries all over the world. They were carried out with bifonazole cream 1%, solution 1%, gel 1% and powder 1%. 49% of the patients treated suffered from dermatophytosis, 30% from cutaneous candidosis and 21% from pityriasis versicolor. The therapeutic efficacy and the tolerability proved good for the indications studied when administered once daily for a treatment period of 2 or 3 weeks. PMID- 6241161 TI - Bifonazole: patch-test trials on local tolerance. AB - Negative test reactions were obtained when 410 eczema patients (129 with allergic contact dermatitis) were tested using occlusion technique with bifonazole in yellow vaseline in the concentrations of 1, 4, 16 and 32%. The latter concentration is 32 times greater than the concentration used therapeutically. Thus bifonazole is not a primary irritant, when applied to the skin under occlusion, nor were any cross reactions observed with allergens previously known. PMID- 6241162 TI - Effect of cimetidine on T lymphocytes in a patient with giant benign gastric ulcer. AB - In view of the findings that Cimetidine, used in the treatment of gastric ulcers, blocks histamine-type 2 receptors, which are also present on T suppressor lymphocytes, a study was carried out in a 65-year-old male suffering from giant benign gastric ulcer and in parallel for control purposes in a healthy male of the same age. T suppressor cells obtained from peripheral blood of the patient were tested prior to institution of treatment with Cimetidine and 21, 62 and 100 days thereafter using 3 different tests - theophylline sensitivity, monoclonal antibodies OKT4 and OKT8 and as a functional test a local xenogeneic graft-versus host reaction (GVHR). The number and percentage of T suppressor cells, which were high before treatment, showed a significant decrease after two months of treatment and this was paralleled by a decrease in suppressor activity and reversal of the functional activity of the T cells from negative to normal. Helper cells were normal before and after treatment. At the same time the patient showed a marked clinical improvement, with healing of the ulcer evidenced by endoscopy. It is suggested that Cimetidine may effect healing by influencing immune mechanisms. PMID- 6241163 TI - Evacuating immobile patients using stairwell slides. PMID- 6241164 TI - Inhouse staff program relieves "back" breaking problems. PMID- 6241165 TI - Study of isovolumic relaxation in man. AB - Although isovolumic relaxation time is relatively short, occupying less than 10% of the total cardiac cycle, study of its duration and of pressure and wall movement changes occurring in it have shed considerable light on the normal synchronous pattern of left ventricular function and its loss in disease. These observations have indicated the importance of diastolic as well as systolic events in determining overall cardiac function, and have stressed the requirement for a more versatile intellectual framework for interpreting these observations than the conviction that all ventricular disease is simply the result of "depressed contractility". PMID- 6241166 TI - [Arrhythmogenic dysplasia of the right ventricle. Description of a case]. AB - A 43 year old man was admitted to our Clinic because of recurrent episodes of palpitation. The electrocardiogram showed incomplete right bundle branch block, frequent ventricular extrasystoles with left bundle branch block morphology and negative T waves in the precordial leads. Two dimensional echocardiography showed marked right ventricular dilatation and right ventricular radionuclide angiography located the enlargment in the infundibulum. Arrhythmogenic right ventricular dysplasia was then suspected. Cardiac angiography excluded the other most common causes of right ventricular dilatation and confirmed the diagnosis. Arrhythmogenic right ventricular dysplasia should thus be regarded as a possible cause of ventricular arrhythmias of unknown etiology. PMID- 6241167 TI - The capacity of antigen-presenting cells is fully preserved in childhood cancer patients. AB - T cells from 19 out of 25 childhood cancer patients showed impaired proliferative responses to purified protein derivatives (PPD)-pulsed antigen-presenting cells (APC) although all of the patients had been immunized with BCG. To test whether such low responsiveness of T cells results from the dysfunction of T cells or from that of APC, the experiment was designed to assess the proliferative response of T cells from patients or their parents to PPD-pulsed APC from patients or parents. These combinations seem to be suitable to assess the activity of T cells or APC since at least partial identity of HLA-D/DR antigens is required for T cell-APC interactions. Although T cells from patients who showed low responsiveness to PPD failed to respond even to PPD-pulsed APC from parents, T cells from parents were able to respond to PPD-pulsed APC from patients as well as to autologous APC. These observations strongly suggest that the low responsiveness to PPD in childhood cancer patients results from the dysfunction of T cells, and the capacity of APC is fully preserved. In other words, it appears that the capacity of APC is not impaired by chemotherapy, neoplastic cells, or other factors. Suppressor T cells appeared not to be involved in such dysfunction of T cells. PMID- 6241168 TI - Cellular immune response in liver of patients with chronic hepatitis B. Electron microscopic observation of lymphocyte subsets by the immunoperoxidase method using monoclonal antibodies. AB - The morphological association between lymphocytes and hepatocytes was studied at the light and electron microscopic levels by the peroxidase-labeled antibody method using mouse monoclonal antibodies against Leu-1, Leu-2a, Leu-3a, Leu-7 and Leu-10 antigens in liver biopsy specimens from patients with chronic hepatitis B. Leu-1 + cells (T cells), especially Leu-2a + cells (cytotoxic/suppressor T cells), infiltrated mostly in periportal areas with piecemeal necrosis and in parenchymal areas with focal necrosis. By double staining techniques, Leu-2a + cells were often seen in contact with hepatocytes containing membranous hepatitis B surface and/or core antigens in patients with chronic active hepatitis. At the ultrastructural level, Leu-2a + cells frequently occupied the sinusoid and also migrated into both the space of Disse and between hepatocytes. Furthermore, they often showed intimate surface-contact with hepatocytes having hepatitis B surface and/or core antigens, and, occasionally, injured hepatocytes were surrounded by several Leu-2a + cells. In contrast, Leu-3a + cells, Leu-7 + cells and Leu-10 + cells sometimes appeared in the sinusoid, but seldom in the space of Disse and between hepatocytes. These findings suggest that cytotoxic T lymphocytes may be associated with the necrosis of hepatocytes in chronic hepatitis B. PMID- 6241169 TI - Nucleotide sequence of the gene, protein purification and characterization of the pSC101-encoded tetracycline resistance-gene-repressor. AB - The nucleotide sequence of the pSC101-encoded tetracycline repressor gene (tetR) was confirmed. The deduced amino acid sequence is compared to that of other repressor proteins. To overproduce the repressor protein, tetR was placed under the control of bacteriophage lambda promoter pL. Tet repressor protein was purified to homogeneity and shown to bind specifically to two tet operators and also to tetracycline (Tc). The inducer function of Tc is demonstrated by the loss of the specific binding between the tet operator DNA and the Tet repressor-Tc complex. PMID- 6241170 TI - Cloning the complete human adenine phosphoribosyl transferase gene. AB - We have isolated a clone from a human genomic lambda library which cross hybridises with the cloned hamster adenine phosphoribosyl transferase gene (aprt). After restriction mapping and further hybridisation to the hamster gene, a series of putative human aprt-containing fragments has been isolated and tested for ability to transform adenine phosphoribosyl transferase-deficient (aprt-) strains of Chinese hamster ovary (CHO) cells to APRT proficiency. Transforming activity was detected in a 48-kb lambda clone, the 17.4-kb EcoRI insert, and an 8.6-kb HincII fragment. Smaller fragments have thus far shown no transforming activity. Transformants appear to be stable for the APRT+ phenotype, and human aprt DNA sequences are present in the hamster transformants. The 8.6-kb HincII fragment has been subcloned and the insert mapped. Nonrepetitive regions of this subclone have been identified, and should prove valuable for chromosome walking studies on human chromosome 16, familial studies of a human aprt- trait, the analysis of restriction fragment length polymorphisms (RFLPs) in the area surrounding the aprt gene, and the fine structure mapping of the mutations induced by chemical carcinogens and alkylating agents. PMID- 6241171 TI - [Effectiveness of a balanced diet in a dispensary for coal miners]. PMID- 6241172 TI - [Hygienic estimation of the working conditions of drift miners during underground geological prospecting in the highland districts of Kirghiz]. PMID- 6241173 TI - [Sanitary-bacteriological characteristics of industrial areas for processing shrimp meat]. PMID- 6241174 TI - [Attitude of patients to prenatal diagnosis based on the example of families with Down's syndrome children]. PMID- 6241175 TI - Synthesized speech rate and pitch effects on intelligibility of warning messages for pilots. PMID- 6241176 TI - Implantable telemetry in biomedical research. PMID- 6241177 TI - The production of interleukin 2 as a measure of reactivity in mixed lymphocyte culture. AB - Interleukin 2 (IL2) produced in vitro in mixed lymphocyte cultures was measured by induction of growth in cells dependent on IL2 for proliferation. The amount of IL2 in early cultures (24 and 48 hours) clearly differentiated the degree of HLA D locus identity between various individuals. Very low amounts of IL2 were produced in cultures between HLA-D identical subjects. The use of IL2 measurement offers a method in the early culture phase for predicting the T cell proliferation which is dependent on the presence of IL2. PMID- 6241178 TI - Disability prevalence in an urban community in relation to socio-economic conditions. PMID- 6241179 TI - The dental management of medically compromised patients. AB - There is an increasing population of apparently well, but in fact medically compromised people in the community. Most will require dental treatment at some stage and will usually seek it away from a hospital environment. In a recent survey of a general dental practice in Australia it was found that up to 55 per cent of some age groups had concurrent medical problems. Thus there is a real risk that adverse interactions between medical conditions and dental treatment may occur--on some occasions, even fatal ones. It is not possible for any one individual to know the details of all medical conditions, their treatment and the possible interactions with dental treatment. However, by the application of some sound general principles the risks of any potential interactions can be evaluated. The essential steps are: knowledge of the medical history of all patients; knowledge of the potential interactions; and knowledge of the management of medical emergencies. These principles will be discussed and illustrated by examples of medically compromised patients who may experience common or potentially serious sequelae as a result of dental treatment. PMID- 6241180 TI - Epidermolytic palmo-plantar keratoderma. AB - An 11-year-old girl who at 9 1/2 months was diagnosed as having keratoderma of the palms and soles, present since birth, developed typical granuloma annulare at the age of 11 years. To the authors' knowledge, this is the first report of epidermolytic palmo-plantar keratoderma associated with granuloma annulare. There was no known family history of keratoderma. A review of the literature revealed three other patients without family history, although most of the patients have had multiple family members with the same problem. Many skin conditions can be associated with epidermolytic hyperkeratosis. The authors believe that epidermolytic palmo-planter keratoderma is a distinct form of palmo-plantar keratoderma rather than a type of ichthyosis. PMID- 6241181 TI - Differential cellular response of resistant and susceptible rodents to the early stages of infection of Taenia taeniaeformis. PMID- 6241182 TI - [The diabetic patient in the dental office]. PMID- 6241183 TI - Distribution of S1-nuclease sensitive sites and double-strand breaks in gamma irradiated lambda-DNA. AB - Double-strand breaks and regions with unpaired bases (S1-nuclease sensitive sites) are formed in the DNA of gamma-irradiated lambda-phages. The frequency of both events was determined in the various fragments produced after digestion with a restriction enzyme (Eco RI). The results show that both types of radiation damage are randomly distributed in the DNA molecule. There is no hint that the S1 sites are formed in preferred regions of the lambda-genome. PMID- 6241184 TI - Hospitals for the disabled. AB - Current policy in the United Kingdom is that disabled people under the age of 65 who require hospital care because of their disability are cared for in hospitals and wards separate from geriatric patients. A number of Young Disabled Units have opened during the past 15 years but have been subject to criticism. This survey suggests that much of the criticism is justified--many units are badly designed, poorly staffed, and have ineffective operational policies. However, some units are attempting to provide a therapeutic and stimulating environment and by emulating them Young Disabled Units may find a useful and uncontroversial role in the spectrum of services for the disabled. PMID- 6241185 TI - International Classification of Impairments, Disabilities and Handicaps: exercises in its application in a hospital medical record. AB - The principles and philosophies of the WHO International Classification of Impairments, Disabilities and Handicaps were enthusiastically espoused by all staff of a large rehabilitation hospital. It was universally seen as an accurate and standardized way of recording and reporting a patient's functional state and opened up opportunities for research between causation and consequences of diseases, the relations of impairments to handicaps, and so on. In short, it promised a hard data base about disability, which presently has been studied only anecdotally, or by large random community samples. The joy of the principle turned into torment when the attempts to apply the system to current and past medical records were made. Retrospective codification of existing records was found to be virtually impossible. Recorded data were patchy, insufficiently precise to translate into IDH codes and the codifier had to make so many value judgements, interpretations and guesses to squeeze what was written on the record into IDH codes. A totally new and disciplined way of making notations in medical records would be required to make this method applicable, and such a discipline presents challenges to the medical administrator which dwarfs the production of the WHO manual.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 6241186 TI - Observations on immune mechanisms in otitis media with effusion. AB - In this brief review of recent advances in immunological reactivity in otitis media, I have neither attempted to review the field from a historical perspective, nor attempted a critical analysis of the current status and future frontiers of this area. I have, rather, reviewed 5 areas that are being pursued in our laboratory and compare our investigations with those being performed throughout the country and abroad. It is my sincere hope that investigations into these areas will continue and will lead to potentially fruitful and meaningful data that will eventually unravel the mystery of persistent OME. PMID- 6241187 TI - Intraoperative monitoring and use of the internal shunt during carotid endarterectomy. AB - Carotid endarterectomy can be an effective form of therapy in stroke prevention in patients with carotid artery disease. A perioperative stroke is not only a devastating complication but negates the beneficial effects of the procedure. Careful attention to detail will prevent embolization during carotid endarterectomy and thus avoid the most common cause of perioperative cerebral infarction. The maintenance of adequate cerebral perfusion during carotid endarterectomy can be provided with the use of a shunt during carotid cross clamping. This is necessary in approximately 15% of patients. Different approaches to the use of a shunt during carotid endarterectomy are discussed with their merits and disadvantages. Assessment of the technical results prior to completion of the operation should be an integral part of the procedure. The available methods, with their inherent limitations, are briefly discussed. PMID- 6241188 TI - [13-cis-retinoic acid. Low dosage oral use in acne papulopustulosa. Results of a multicenter study]. AB - Successful treatment of acne conglobata with 13-cis-retinoic acid (isotretinoin, Ro 4-3780) has already been reported in this journal [25, 36]. The aim of the present study was to treat severe forms of papulopustular acne, unresponsive to conventional therapy, with low doses of 13-cis-retinoic acid to obtain good results with few side effects. A total of 191 patients from 14 departments of dermatology in the Federal Republic of Germany received 13-cis-retinoic acid under open randomized conditions in parallel dose groups of 0.05, 0.1, and 0.2 mg/kg body weight for 20 weeks in order to establish efficacy and tolerance. All inflammatory and non-inflammatory skin lesions were counted. The intensity of seborrhea was graded by using a scale. Adverse effects as well as laboratory values were registered. After 20 weeks of treatment a 79% (0.05 mg), 80% (0.1 mg), and 84% (0.2 mg) decrease in the number of inflammatory skin lesions was seen. Fourteen patients in the lowest dose group were considered to be dropouts. The decrease in non-inflammatory skin lesions was less marked and amounted to between 49% and 69%. A significant reduction of seborrhea could be observed in all patients. The main side effect was dryness of the skin and mucous membranes, which was, however, of low intensity. The elevation of triglyceride and cholesterol levels reported with higher doses of 13-cis-acid, especially in patients with high-risk factors, were not encountered in this study. PMID- 6241189 TI - Long-term follow-up of hip arthrodesis performed in young patients. PMID- 6241190 TI - Lead induced histochemical changes in the testes of rats. PMID- 6241191 TI - Spenolimycin, a new spectinomycin-type antibiotic. I. Discovery, taxonomy and fermentation. AB - Spenolimycin, a new spectinomycin-type antibiotic, was discovered in the fermentation broth of a new actinomycete named Streptomyces gilvospiralis sp. nov. strain AB634D-177. Although a small amount of spectinomycin is coproduced by strain AB634D-177, the culture is different from other known spectinomycin producing actinomycetes. Spenolimycin was obtained by conventional submerged culture in 14-liter fermentors with a peak antibiotic titer of 140 micrograms/ml. PMID- 6241192 TI - Spenolimycin, a new spectinomycin-type antibiotic. II. Isolation and structure determination. AB - A new water-soluble, basic antibiotic has been isolated from the fermentation beers of Streptomyces gilvospiralis sp. nov. The structure of the antibiotic has been deduced from spectral studies and confirmed by chemical degradation to spectinomycin. This structure, 3'-O-methylspectinomycin-3',4'-enol ether has led to the name spenolimycin. PMID- 6241193 TI - Spenolimycin, a new spectinomycin-type antibiotic. III. Biological properties. AB - Spenolimycin is a new spectinomycin-type antibiotic isolated from Streptomyces gilvospiralis sp. nov. In vitro, it was active against a wide variety of aerobic Gram-positive and Gram-negative bacteria and Neisseria gonorrhoeae. It was two to four-fold more active against N. gonorrhoeae than spectinomycin. Spenolimycin was effective in the standard mouse protection test against Escherichia coli, Klebsiella pneumoniae and Streptococcus pneumoniae. PMID- 6241194 TI - Effect of purified zearalenone on early gestation in gilts. AB - Purified zearalenone (Z) was added to the diet of gilts from d 2 to 15 postmating. Gilts received either 0, 5, 15, 30, 60 or 90 ppm Z (three to five gilts per dose) in 1.8 kg of feed daily. Serum concentrations of progesterone and estradiol-17 beta were determined weekly. On d 13 to 15 and 40 to 43 postmating, blood samples were drawn from a cannula at 20 min intervals for 4 h and analyzed for luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin (PRL). Gilts were killed 40 to 43 d postmating and embryonic development was assessed. Treatment with 5, 15 or 30 ppm Z had no effect on embryonic development when compared with 0 ppm. No fetuses were present in gilts fed 60 to 90 ppm Z, but two gilts given 60 ppm Z had remnants of fetal membranes in the uterus. The histologic appearance of reproductive tract tissues from the gilts given 60 ppm Z was similar to that from pregnant gilts. Tissues from gilts given 90 ppm Z appeared to be stimulated by both estrogen and progesterone. Serum concentrations of progesterone were decreased at 2, 3 and 6 wk postbreeding in gilts fed 60 and 90 ppm Z. Serum concentrations of estradiol-estradiol-17 beta were decreased at 4 wk postbreeding in gilts fed 60 and 90 ppm Z.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 6241195 TI - Using mini peak flow meter. A simple airway monitor in respiratory medicine. PMID- 6241196 TI - Mechanical properties of fast and slow skeletal muscle with special reference to collagen and endurance training. AB - The mechanical properties of the slow soleus and the fast rectus femoris muscle under passive stretching were studied in endurance trained, untrained and lathyritic rats, aged 3 months. The soleus muscle with more abundant and cross linked collagen had higher ultimate tensile strength and tangent modulus compared to the fast rectus femoris muscle which, on the other hand, had higher maximum strain. The inhibition of collagen cross-linking by lathyrism resulted in decreased tensile strength and stiffness, especially in the soleus muscle, whereas endurance training showed the opposite effects. It is supposed that the properties of collagen partly explain the capacity of slow muscles to maintain posture and to perform prolonged dynamic work. The effects of training on the tensile properties further indicate the close relationship between intramuscular collagen and the endurance capacity of muscles. PMID- 6241197 TI - Intestinal stomal dilatation. AB - Dilatation of 23 surgically created gastrointestinal tract stomata in 21 patients has been performed using angioplasty techniques. A success rate of 44% was achieved in nine patients with gastric stapling and Marlex mesh wrapping of the greater curve stoma. In 13 patients with gastric stapling, and either sutured gastro-gastrostomy or roux-en-y gastro-jejunal bypass, a success rate of 77% was achieved. In one patient with a jejunostomy, stenosis dilatation was also successful. PMID- 6241198 TI - Cross-mesh radiopaque grid for localization of segmental coronary artery disease during transluminal angioplasty. AB - A simple, inexpensive radiopaque cross-mesh grid has been devised to assist in localization of coronary artery lesions for placement of balloon catheters during percutaneous transluminal coronary angioplasty. The grid is made of radiopaque lines encased in a flexible plastic. In use this grid is placed on the patient's chest and provides multiple landmarks without obscuring vascular detail. The grid has been in use here for more than six months and has proven to be a helpful tool. PMID- 6241199 TI - [Post-traumatic eventration in the child. Apropos of 3 cases]. PMID- 6241200 TI - Resolution of RS-abscisic acid and the separation of abscisic acid metabolites from plant tissue by high-performance liquid chromatography. AB - Attempts to resolve the enantiomers of racemic abscisic acid (ABA) by high performance liquid chromatography on a chiral stationary-phase column were unsuccessful. However, reduction of RS-methyl ABA (RS-Me-ABA) with sodium borohydride generates a new chiral centre and one of the two isomeric products, the RS-Me-1',4'-cis-diol of ABA, was separated into its enantiomers by high performance liquid chromatography on an optically active Pirkle column. High performance liquid chromatography on a mu Bondapak C18 column separated the metabolites and conjugates of [2-14C]ABA fed to tomato shoots. The resolution method was used to measure the relative proportions of R and S enantiomers in the free acid liberated from conjugates of ABA. PMID- 6241201 TI - The assessment of subjective tension levels among several muscle groups: the tension mannequin. AB - The present paper introduces the Tension Mannequin, a self-report questionnaire on which tension levels of various muscle groups are rated. In Experiment 1 this instrument was administered to 44 normal adults preceding and following relaxation training. Questionnaire results revealed that subjects used three tension level ratings across muscles. Only 14% of the sample rated all muscle groups identically. Pre-training correlations between the individual muscle ratings and a general rating of tension suggested that the general rating was made by averaging tension in various muscle sites. The questionnaire appeared to be sensitive to the effects of relaxation training since pre- and post comparisons of all muscle groups were significantly different. Experiment 2 investigated whether the questionnaire would differentiate subjects suffering at least three tension headaches per week from those reporting less than three. Results revealed that the frequent headache group had greater subjective tension in the forehead and neck. A case example illustrates how the Tension Mannequin revealed the importance of back discomfort to a patient's experience of tension headaches and general tension. PMID- 6241202 TI - The epidemiology of depression. An update on sex differences in rates. AB - Data from the New Haven, CT, Standard Metropolitan Statistical Area, site of the NIMH Epidemiologic Catchment Area (ECA) study, a multi-site collaborative community survey of psychiatric disorders is presented. The 6-month prevalence rates based on the Diagnostic Interview Schedule (DIS) interview and the DSM-III found that major depression was more frequent in women than men (2.4:1). The sex ratios for bipolar disorder were about equal. The sex ratios for major depression were fairly consistent at different time periods retrospectively assessed. There appeared to be a birth cohort effect with cohort's born after 1936 having an earlier age of onset and higher rates of major depression but not a change in sex ratios. These findings must be considered in light of the methodologic limitations of retrospective recall. PMID- 6241203 TI - Do the diagnostic criteria determine the sex ratio in depression? AB - The 1-year prevalence rates and sex ratio of dysphoric mood, brief (BDE, less than 2 weeks) and extensive (EDE, greater than or equal to 2 weeks) depressive episodes and major depression (RDC, DSM-III) from an epidemiologic study are presented. Factors influencing the sex ratio are analyzed: subjective suffering from EDE, social and work impairment were found to an equal degree in both genders. Factors favoring female preponderance: women report more symptoms, men most probably forget symptoms, frequency and length of less recent depressions more readily, women see a physician or proceed to self-medication much more often. Consequently, the identical minimum symptom number for both genders is questioned and occupational impairment suggested as an alternative case-defining criterion. PMID- 6241204 TI - Sex-related differences in depression. Familial evidence. AB - After a description of threshold models of familial transmission based on an underlying continuous liability distribution, family data from the NIMH-CRB Collaborative Psychobiology of Depression Program-Clinical are described. No sex differences are found for bipolar illness, whereas female relatives have an increased rate of primary unipolar illness when compared to male relatives. This effect persists when relatives are classified according to recurrence, current illness, onset within the last 10 years, and treatment. Moreover, a cohort effect is present in the data and indicates a sex ratio close to one in the young cohort (less than or equal to 25). We considered the transmission of illness from parent to offspring by using survival analysis to examine the proportion of ill brothers and sisters of probands according to the affection status of parents. A maternal effect is found, with the mother having a greater influence on the liability of offspring of either sex. This is at odds with the notion that males and females have identical liabilities, but females have a lower threshold reflecting acknowledgement of more symptoms, etc. However, the mean difference in liability between the sexes may be due to systematic biological/cultural differences, with parental transmission contributing to variation about their means. PMID- 6241205 TI - Personality and gender-related differences in depression. AB - Seventy recovered female nonbipolar depressed patients and 32 recovered males were individually matched for age, sex and marital status with never mentally ill control subjects. Difference scores on personality scales indicative of interpersonal dependency, learned helplessness, and other features were compared for female patients and their matched controls, vs male patients and their controls. The difference between patients and controls was not less for females than for males. Thus the hypothesis that the higher prevalence of depression in women is due to the fact that their general personality features resemble those associated with a predisposition to depression was not supported. PMID- 6241206 TI - Gender differences in antidepressant and activating drug effects on self perceptions. AB - Gender difference in neuropharmacologic responsivity have received surprisingly little attention in clinical research. In view of well-known gender differences in the prevalence of depression, we wondered whether men and women would respond differently to antidepressants or to an activational drug known to predict antidepressant response. Using clorgyline and D-amphetamine in 2 small samples, we illustrated several methodological approaches for examining possible gender linked differences in the effects of these drugs on self-perceptions. Gender linked differences in cognitive-perceptual processes may, in turn, be linked to differences in encoding or consolidating information about our experiences into our self-image for later recall. PMID- 6241207 TI - The present status of unilateral ECT. Some recommendations. PMID- 6241208 TI - The relationship of EEG sleep to vital depression. AB - EEG sleep and clinical characteristics of 111 depressed inpatients with primary unipolar depression were examined in relation to several proposed definitions of endogenous depression (RDC criteria; DSM-III melancholia; and Nelson-Charney criteria). While each of these clinical schema demonstrated specific relationships to the EEG sleep findings in the overall group, the group with DSM III melancholia showed definite REM sleep abnormalities, especially with REM activity and distribution. Further studies with sleep, neuroendocrine, and neurochemical measures are indicated in order to confirm the biologic 'substrate' of melancholia or vital depression. PMID- 6241209 TI - Decreased erythrocyte membrane elevations in patients with a major depressive episode. AB - Washing of erythrocytes from healthy volunteers in an isotonic sodium chloride solution at pH 5.6 results in the occurrence of plasma membrane elevations as observed in freeze-etch electron microscopy. This is prevented by anion permeability inhibiting agents. In the absence of these agents a reduced number of elevations was found in 23 of 36 patients with a major depressive episode. This reduced capacity to form membrane elevations was positively correlated with a genetic vulnerability, defined as an admission to a psychiatric hospital in first-degree relatives. PMID- 6241210 TI - The dexamethasone suppression test in acute mania. AB - The dexamethasone suppression test was administered to 40 newly admitted manic patients. Twenty-four patients (60%) had abnormal escape from suppression. There was no correlation of DST results with sex, age, age of onset, family history of affective disorder, psychosis during index episode, or duration of hospitalization. DST non-suppressors were significantly more likely than suppressors to be discharged on lithium alone. PMID- 6241211 TI - A double-blind comparison of fluvoxamine, imipramine and placebo in depressed patients. AB - In a placebo-controlled, double-blind study of 91 out-patient depressives, the anti-depressant effect of fluvoxamine, a selective serotonin uptake inhibitor was compared to that of imipramine. Overall drug effects were relatively weak but analyses in selected sub-groups showed both active drugs superior to placebo. Effects of fluvoxamine were more marked in non-situational depressives and it did not improve sleep while effects of imipramine were more marked in retarded depressives and on retardation ratings, suggesting that fluvoxamine may have a different pattern of clinical effects. Side effects of Fluvoxamine were predominantly gastrointestinal and it did not produce postural hypotension or anticholinergic side-effects. PMID- 6241212 TI - The implications of DSM-III personality disorders for patients with major depression. AB - We studied 78 inpatients with DSM-III major depression. Forty-one (53%) had a concurrent personality disorder (PD) according to a detailed structured interview for DSM-III personality disorders. The patients with depression plus PD differed from patients with depression alone on numerous measures. The PD patients had earlier onset; higher HRS scores; poorer social support; more life stressors; more frequent separation and divorce; more frequent nonserious suicide attempts, less frequent dexamethasone nonsuppression; poorer response to antidepressant medication; and higher risk for depression, alcoholism and antisocial personality among first-degree relatives. The PD subgroup shares many attributes with Winokur's subtype of depression spectrum disorder and Akiskal's character spectrum disorder. An attempt to identify a subgroup of personality disorders which might be an atypical affective disorder was inconclusive. However, patients in DSM-III cluster III were similar to the patients with no-PD on the dexamethasone suppression test, response to treatment, and familial risk for depression and antisocial personality. PMID- 6241213 TI - Parental bonding in bipolar affective disorder. AB - When the Parental Bonding Instrument was administered to 58 bipolar affective disorder patients and 100 general practice patients no difference was found in reports of parental characteristics. Among the female patients there was an association between poor parental bonding and increased number of hospitalisations. PMID- 6241214 TI - Vasoactive intestinal polypeptide decreased in cerebrospinal fluid (CSF) in atypical depression. Vasoactive intestinal polypeptide, cholecystokinin and gastrin in CSF in psychiatric disorders. AB - Vasoactive intestinal polypeptide (VIP), cholecystokinin (CCK) and gastrin in the cerebrospinal fluid (CSF) were studied in patients with endogenous depression, non-endogenous depression, mania, schizophrenia and a control group. All patients were classified according to ICD-9 and the group of depressions was further classified according to the Newcastle Rating Scales for depression (Carney et al. 1965) (N-I). In the group of non-endogenously depressed patients, CSF-VIP levels (median 16 pmol/l) were found to be significantly lower than those of controls (median = 32 pmol/l) and endogenous depressives (36 pmol/l). In the non endogenous group, it appeared that the low CSF-VIP was due to a group of patients who, during a past or present depressive episode, had been diagnosed as suffering from endogenous depression. Moreover, this group was clinically characterized by 'dysphoric/hysterical features', 'reversed diurnal variation' (i.e. worse in the evening), and 'lack of clearly circumscribed episodes'. In many aspects this group seems similar to the atypical depressives described as monoamine oxidase inhibitor responders. Concerning CSF-CCK and CSF-gastrin, no significant differences between the examined groups were demonstrated. PMID- 6241215 TI - Treatment of bipolar affective illness with zimeldine, a 5-HT uptake inhibitor. AB - A small group of patients who had been successfully treated with lithium for a number of years were treated with zimeldine in order to determine whether this antidepressant could be substituted for lithium in patients with a bipolar affective illness. The proposed treatment period of 6 months was not reached by any patient due to depression, hypomania, mania or unusual adverse symptoms. The results of this pilot study suggest that bipolar patients being treated with lithium should not then be treated by antidepressants including those which are potent and selective inhibitors of 5-HT uptake. PMID- 6241216 TI - [Laparoscopy in the diagnosis and treatment of adnexal torsion]. AB - 13 uterine adnexal torsions were diagnosed by means of laparoscopy between June 1978 and October 1982. Laparoscopy is an opportunity for the adnexae to be untwisted, and gives precision to estimate the severity of the damage of the adnexae and to elucidate the aetiology. In ten patients, the treatment was performed by means of laparoscopy Three patients underwent immediate laparotomy: two for necrosis of the adnexae, one for a mucinous cystadenoma. The post operative course was always uneventful. A second look laparoscopy was performed to check the anatomical recovery of primary severe ischaemic lesions (4 cases). The usefulness of laparoscopy in diagnosing torsion of the uterine adnexae is now well established. We can also treat by means of laparoscopy. Contra-indications to this management are necrosis of the adnexae and organic tumours. PMID- 6241217 TI - Investigations on the age-dependence of T-lymphocyte subpopulations and lymphocyte reactivity. AB - The percentage T-lymphocyte subpopulations were determined with the aid of radioactively-labelled monoclonal antibodies to the antigens of total T lymphocytes and to suppressor T-lymphocyte surface antigens and the responsiveness of the lymphocytes in the presence of ConA and PHA was investigated in groups of 8 subjects aged either between 20 and 30 years or over 75 years. It was found that there was no difference with respect to the response of the lymphocytes to the plant mitogens ConA and PHA. The percentage of suppressor T-lymphocytes, on the other hand, was significantly reduced in the older subjects, whilst the percentage of total T-lymphocytes did not differ significantly from the percentage in younger subjects. These results are discussed in connection with published data. PMID- 6241218 TI - [Clofezone and oxyphenbutazone excluded from dental use]. PMID- 6241219 TI - [Clinical evaluation of a gingival massage agent (LPD) on gingivitis and marginal periodontitis using a double blind method]. PMID- 6241220 TI - [The oral health status and the detectable dental needs of totally blind persons]. PMID- 6241221 TI - [Transcutaneous measurement of blood flow in arteriovenous fistulae caused by hemodialysis using Doppler ultrasound]. AB - Blood flow measurement in arterio-venous fistulae can be performed with a duplex ultrasound system which combines echography and C. W. Doppler. This method is very useful to follow up the patency of the fistulae and his consequence on the cardiac function. The exploration consists in two steps: a qualitative study of the Doppler spectrum to detect a possible decrease of the arterial diastole flow which traduce a severe stenosis; the evaluation of the blood flow in ml/min. The blood flow in ml/mn is a good parameter for the follow-up of the fistulae; moreover in case of high blood flow values, it is very useful to guide the surgical therapy. PMID- 6241222 TI - [Ultrasound measurement of portal blood flow. Initial results in the study of hemopathies]. AB - Portal blood volume was non invasively evaluated with pulsed Doppler ultrasound coupled with automatic, water path echotomography (U. I. Octoson). This measurement was successful in 18 from 24 normal volunteers, the portal flow values being 14.25+ or -4.5 ml/min/kg. The portal blood flow measurement was possible in 16 from 17 patients with hemopathy. Portal flow volume was greatly increased in 11 cases (more than 23 ml/min/kg), in connection with splenomegalia. It was moderately high in 3 cases, from whom 1 without splenomegalia and 1 splenectomised. Portal flow was normal in 1 case and was reduced in 1 case (with high splenic blood flow, in a patient with portal hypertension due to portal vein compression by adenopathy). Portal blood flow increase seems to be connected with splenomegalia. Manometric portal hypertension seems to be more clearly connected with hepatic invasion by hemopathy. PMID- 6241223 TI - [Simultaneous use of ultrasound and pulsed Doppler with spectrum analysis of frequency in diseases of the cervical and cerebral vessels. Initial results]. AB - Preliminary results of the use of the ultrasound Duplex Scanner are reported and correlated with angiographic findings. The main interest of this examination resides in its application in cases of atheromatous obstruction of cervical vessels to the brain: definition of type of obstruction: occlusion or stenosis; assessment of hemodynamic alterations: modification of frequency spectrum, of pulsed Doppler signal to 5 degrees as defined by Strandness as a function of extent of narrowing of arterial lumen. Pre-occlusive lesions may be difficult to distinguish from an occlusion. In contrast, minor anomalies: plaque producing little or no stenosis, calcifications, appear to be simpler to detect than by angiography. In intracranial vascular malformations: arteriovenous fistulas and particularly intracranial angiomas of a certain size, this examination provides data on the increase in diameter and acceleration of flow in vessels supplying the malformation. In cases of brain death, the ultrasound Duplex Scanner demonstrates absence or marked reduction in internal carotid artery flow, whereas flow is normal in the external carotid arteries in the absence of collapse. Confirmation of reliability of this non-invasive exploratory procedure requires further evidence of correlations. PMID- 6241224 TI - [Ultrasound in the study of fetoplacental circulation]. AB - Exploration of fetal vessels is performed with a duplex system which combines a real-time linear imaging system 3.5 MHz and a pulsed Doppler (2.5 MHz). The transducers of the imaging and Doppler systems are associated in the same probe. Umbilical and aortic circulation have been investigated on 100 pregnancies. The umbilical artery Doppler spectrum shows an important diastolic flow which increases all along the pregnancy. A decrease of this flow occurs when the placental circulatory resistances increase. In case of severe hypertension one can note a decrease or the disappearance of the diastolic flow related to the existence of vascular placental defects (infarctus). This was observed in pathological pregnancies with hypotrophy or fetal death. The placental resistances can be quantified with the Pourcelot index R = A - D divided by A, where A is the maximum systolic amplitude and D the maximum end diastolic amplitude, both measured on the umbilical artery spectrum. Fetal blood flow measurements were performed with the same device. The mean value of the blood flow is about 170 ml/min/kg in the aorta and 120 ml/min/kg in the umbilical arteries at the end of the pregnancy. The possibility to record simultaneously fetal aorta and inferior vena cava enable us to detect abnormal heart rate such as the atrioventricular block. PMID- 6241225 TI - The causes of fixed drug eruption. PMID- 6241226 TI - Calcium antagonist binding sites in the rat brain: quantitative autoradiographic mapping using the 1,4-dihydropyridines [3H]PN 200-110 and [3H]PY 108-068. AB - An in vitro autoradiographic technique has been used for the quantitative mapping of calcium antagonist binding sites (CABS) in the rat brain, using the 1,4 dihydropyridines [3H]PN 200-110 and [3H]PY 108-068 as ligands. CABS were distributed throughout the brain in a highly heterogeneous fashion. The highest densities of CABS were observed in the olfactory bulb, hippocampus and parts of the amygdala. The neocortex was also rich in CABS. The basal ganglia, thalamus and hypothalamus presented intermediate levels of CABS while low densities of sites were seen in areas such as the cerebellum, pons and white matter tracts. The distributions of CABS in brain does not correlate with indexes of brain blood flow, regional glucose utilization or the distributions of receptor binding sites for drugs and neurotransmitters analyzed until now. No correlation exists between CABS distribution and that of any neurotransmitter or brain enzyme described so far. The heterogeneous distributions of CABS is suggestive of a neuronal localization, an idea supported by lesion experiments. PMID- 6241227 TI - Repeated treatment with antidepressant drugs increases the behavioural response to apomorphine. AB - The effect of repeated treatment (twice a day for 14 days) with antidepressant drugs (AD): imipramine, amitriptyline, zimelidine, citalopram and mianserin on the behavioural response to apomorphine in rats (open field test) was investigated. AD studied, given alone in a single dose or repeatedly, do not change the rats behaviour. A repeated but not single-dose treatment with AD facilitates the behaviour stimulation induced by apomorphine. This facilitation is observed 2 hours after the last dose of imipramine, zimelidine, citalopram and mianserin but 72 hours after the last dose of amitriptyline. The results presented suggest that the AD given repeatedly are able to increase the responsiveness of the brain DA system, probably the mesolimbic one. PMID- 6241228 TI - Cell to cell interactions of Capnocytophaga and Bacteroides species with other oral bacteria and their potential role in development of plaque. PMID- 6241229 TI - Effects of the association of conventional rats with Actinomyces viscosus Nyl and Bacteroides gingivalis W83. PMID- 6241230 TI - Mediators of bacterial virulence in chronic adult periodontitis. PMID- 6241231 TI - Suspected periodontopathic organisms alter in vitro proliferation of endothelial cells. PMID- 6241232 TI - Phenotypic studies of cells from periodontal disease tissues. PMID- 6241233 TI - Abnormal leukocyte motility in patients with early-onset periodontitis. PMID- 6241234 TI - T lymphocyte subsets in the inflamed gingiva of human adult periodontitis. PMID- 6241235 TI - Local and systemic production of immunoglobulins to periodontopathogens in periodontal disease. PMID- 6241236 TI - A study of antibodies and opsonic activity in human crevicular fluid in relation to periodontal disease. PMID- 6241237 TI - The relationship of antibody response categories to clinical parameters of periodontal disease. PMID- 6241238 TI - Specific serum antibody levels and periodontal destruction. A double blind correlation analysis in Red Cross blood donors. PMID- 6241239 TI - Diagnostic potential of chromogenic substrates for rapid detection of bacterial enzymatic activity in health and disease associated periodontal plaques. PMID- 6241240 TI - The relationship of complement cleavage in gingival fluid to periodontal diseases. PMID- 6241241 TI - Determination of periodontal disease activity by a bone resorption assay. PMID- 6241242 TI - Non-steroidal anti-inflammatory drug treatment of periodontitis in beagles. PMID- 6241243 TI - Immunohistological localization of collagen (I and III) and fibronectin in inflamed and non-inflamed gingival connective tissue and sulcular fluid of beagle dogs. PMID- 6241245 TI - The role of epithelial-mesenchymal interactions in epithelial migration and differentiation. PMID- 6241244 TI - Fibroblast subtypes in the periodontium. A possible role in connective tissue regeneration and periodontal reattachment. PMID- 6241246 TI - Cell migration attachment and orientation in vitro are enhanced by partial demineralization of dentine and cementum and inhibited by bacterial endotoxin. PMID- 6241247 TI - New attachment formation on citric acid and non-citric acid treated roots. PMID- 6241248 TI - Induction of hyperpyrexia by dihydrocurvularin, a metabolic product of Penicillium gilmanii. AB - The previously reported rise in rectal temperature that follows the intravenous injection of the mixture of metabolic products (extractable with ether from the Czapek Dox medium on which Penicillium gilmanii has grown) is due to a single compound, dihydrocurvularin. Intravenous injection of 1-10 micrograms of dihydrocurvularin into rabbits causes a rise of at least one degree in rectal temperature of rabbits in 2-8 h. The degree of temperature rise depends more on the individual rabbit than on the quantity of dihydrocurvularin injected. Treatment with lipopolysaccharide abolishes the ability of dihydrocurvularin to cause a rise in rectal temperature. Treatment with dihydrocurvularin, however, does not abolish the ability of lipopolysaccharide to induce a temperature response or a leukocytosis. Rabbits respond to repeated treatment with dihydrocurvularin with a rise in rectal temperature that is indistinguishable from that observed on their first injection. Treatment with dihydrocurvularin does not affect differential counts or the concentration of leukocytes or red blood cells in the circulatory system. PMID- 6241249 TI - A study of the relationship between muscle length, tension-time area and stiffness in cat areflexic soleus. AB - The relationship between muscle length and both tension-time area and stiffness were studied in the isolated cat soleus muscle during tetanic isometric contraction at different stimulus rates. The results show that: The area subtending the tension curve remains constant in a range of 8-10 mm of muscle length, for stimulation frequencies between 15 and 66 Hz. The muscle stiffness, measured using different amplitude stretches, remains constant over changes in muscle length of 10 mm. The stiffness is higher for smaller stretches than for larger ones. The data therefore show an approximately constant tension-time area and no significant changes in stiffness for variations in muscle length that exceed the physiological length variations during quiet standing. These results are discussed in the context of postural mechanisms. PMID- 6241250 TI - Research on what? PMID- 6241251 TI - Primary actinomycosis of the anterior abdominal wall (a case report). PMID- 6241252 TI - Study of cancer of the breast in Burma. PMID- 6241253 TI - Quantitative receptor autoradiography: application to the characterization of multiple receptor subtypes. AB - In vitro autoradiographic techniques combined with computer assisted microdensitometry were used to analyze the characteristics and distribution of multiple recognition sites for the neurotransmitters acetylcholine (M1 and M2) and serotonin (5-HT1A and 5-HT1B). For this purpose, binding competition experiments were performed using non-subtype selective 3H-labeled ligands and selective unlabeled compounds. Consecutive tissue sections were incubated in the presence of increasing concentrations of displacers. By using this approach, maximal densities of binding sites, as well as competition profiles of several drugs could be analyzed and quantified in microscopic brain areas. Our results reveal the presence of brain structures enriched in one class of muscarinic or serotonergic-1 recognition sites. This provides a tool for better characterization of the proposed "subtype-selective" ligands and suggests physiological functions for these receptor subtypes. It is concluded that quantitative autoradiographic techniques provide a level of anatomical and pharmacological information on neurotransmitter receptor subtypes, which is difficult to attain using membrane binding studies. PMID- 6241254 TI - Lasers in medicine and surgery. AB - The laser produces an intense beam of pure monochromatic light. The wavelength of the light determines its effects on body tissues, and this defines the clinical role of each laser. The carbon dioxide laser is absorbed by water and it is used as a high precision, bloodless, 'light scalpel'. The blue/green argon laser beam is absorbed by structures which have its complementary colour red, and it can coagulate vessels through the without damage to clear, normal tissues. The neodymium: YAG laser is deeply absorbed in the tissues, and is used both for vessel coagulation and thermal tissue destruction. The tunable dye laser is used to photoactivate intra-tumour haematoporphyrin derivative in the treatment of many forms of malignant disease by photoradiation therapy. Lasers should only be used when they offer significant advantages over established conventional techniques, and this paper attempts to define the areas in which lasers offer these advantages. PMID- 6241255 TI - A non-invasive CSF flowmeter. AB - A new non-invasive method for quantitative measurement of cerebrospinal fluid (CSF) flow in the ventriculo-peritoneal shunt tubing, used in hydrocephalus, has been developed. It is an implantable device which produces a bubble in the shunt tubing by electrolysis. This bubble is then detected in the tubing by an electrode arrangement using electric impedance or ultrasonically using a Doppler probe. The energy for electrolysis is supplied by extracorporeal high-frequency transmission. The CSF flow rate is calculated by the velocity of bubble flow in the tubing. CSF flow rates, ranging from 0.01 to 1.00 ml/min, have been measured in animal experiments with statistically good accuracy. In 11 clinical cases a flow range of between 0.01 and 1.93 ml/min have been observed. PMID- 6241256 TI - The use of microcomputers for psychological assessment of physically disabled adults. AB - Many severely physically disabled people are unable to be psychologically assessed by conventional methods because of the severity of impairment, yet the information gained from such assessment can be very valuable in the planning of programmes to improve the individual's condition. We are developing a microcomputer-based system to enable severely disabled people to be psychologically assessed and this paper reports on the system developed for this purpose. PMID- 6241257 TI - Immobilized IgG-aggregate-induced cytolytic activity of lymphocytes from patients with rheumatoid arthritis. AB - T-depleted lymphocytes can lyse nonsensitized target cells subsequent to interacting with immobilized IgG-aggregate, while T cells from healthy individuals can suppress this cytolytic response. In the present study we have compared the activity of non-T effector cells and T suppressor cells from the peripheral blood of healthy individuals with that of cells from the peripheral blood and synovial fluids of patients with rheumatoid arthritis (RA). Unlike peripheral blood lymphocytes (PBL) from healthy donors, which were never lytic without removing T suppressor cells, PBL from RA patients were occasionally active without removing T cells; lymphocytes from joint fluids were almost always active. The lytic response of RA joint fluid lymphocytes could be suppressed by T cells from autologous or healthy donor peripheral blood, thus suggesting that the suppressor cell which regulates this lytic mechanism might be defective or absent in joint fluids of RA patients. PMID- 6241258 TI - Occurrence of developmental morphological defects in permanent teeth of mentally retarded children. AB - A group of 9- to 11-year-old mentally retarded children (n = 92) and randomly selected healthy controls of the same age (n = 67) were psychologically tested for mental performance and examined for developmental morphological defects in their permanent teeth. About twice as many teeth with developmental defects in crown morphology were found in the retarded children as in healthy children. In retarded children, the frequency of defective dental crowns increased with the severity of mental retardation, as measured in terms of IQ. Owing to modifying factors that affect IQ, however, this trend can be questioned. PMID- 6241259 TI - Selenium and glutathione peroxidase in plasma and erythrocytes of Down's syndrome (trisomy 21) patients. PMID- 6241260 TI - Maternal influence on the task behaviour of young Down's syndrome children. AB - Twenty-one Down's syndrome children (mean CA 45.5 months, SD 12.4; mean MA 24.8 months, SD 7.5) and 13 control children (mean CA 39.9 months, SD 11.6) played with a box which had 10 doors each secured by a different locking device. There were two conditions, one in which their mothers were free to interact with them and one where maternal involvement was restricted. Results showed that mental age was significantly associated with measures of competence and organization. When MA was partialled out as a covariate, group differences remained for the competence measures, relocking behaviours, and aimless actions. The involvement of the mother had a significant effect only in decreasing the aimless actions of the Down's syndrome children. PMID- 6241261 TI - Selective auditory preferences and the use of automated equipment by severely, profoundly and multiply handicapped children. AB - Using automated equipment, contingent responding and auditory preferences were examined in 15 severely, profoundly and multiply handicapped children (CMAs 3-20 months) and 2 non-handicapped children at ages 5.0 and 9.5 months. 15 children showed contingent responding; prolonged responding was shown by the profoundly handicapped group. Where auditory preferences were apparent, they were the same as those seen in Down's syndrome and non-handicapped groups at the same developmental level. Children at the 5 months developmental level and less, had difficulty in making choice responses. Implications for intervention are discussed. PMID- 6241262 TI - Long poly(A) tracts in the human genome are associated with the Alu family of repeated elements. AB - Long poly(dA).poly(dT) tracts (poly(A) tracts), regions of DNA containing at least 20 contiguous dA residues on one strand and dT residues on the complementary strand, are found in about 2 X 10(4) copies interspersed throughout the human genome. Using poly(dA).poly(dA) as a hybridization probe, we identified recombinant lambda phage that contained inserts of human DNA with poly(A) tracts. Three such tracts have been characterized by restriction mapping and sequence analysis. One major poly(A) tract is present within each insert and is composed of from 28 to 35 A residues. In each case, the poly(A) tract directly abuts the 3' end of the human Alu element, indicating that the major class of poly(A) tracts in the human genome is associated with this family of repeats. The poly(A) tracts are also adjacent to A-rich sequences and, in one case, to a polypurine tract, having the structure GA3-GA3-GA4-GA6-GA5-GA4. We suggest that repetitive cycles of unequal crossing over may give rise to both the long poly(A) and polypurine tracts observed in this study. PMID- 6241263 TI - Structural comparison of purified dynein proteins with in situ dynein arms. AB - Using the quick-freeze deep-etch technique, we describe the structure of outerarm dynein proteins from Chlamydomonas and Tetrahymena after adsorption to a mica surface, after high-salt dissociation, and after glutaraldehyde fixation, and compare these images to the configuration of outer arms bound to microtubules. After adsorption to mica, the extracted dyneins from both organisms look like three-headed "bouquets", as reported for Tetrahymena by Johnson & Wall (1983b). High magnification images demonstrate that each head carries a slender "stalk" and a long "stem", and that small subunits decorate the stems and create a "flowerpot" domain at the base of the bouquet. Exposure to high salt induces this trimer to dissociate into a two-headed species and a single-headed species; it also stimulates the decorative elements to dissociate from the stems. Dynein is thus constructed on the same general plan as myosin, with large globular heads, narrow stems and additional small subunits that associate with the stems. The splayed-out image of the bouquet appears to be a distortion arising during adsorption to mica since, after brief glutaraldehyde fixation, the three heads remain closely associated as vertices of a triangular unit. In situ, the three heads also adopt this trigonal configuration. Two of the three are visible from the exterior of the axoneme and constitute the bilobed rigor head we described previously (Goodenough & Heuser, 1982). The third head faces the interior of the axoneme where, we propose, it forms the "hook" of the outer arm as seen in thin section. We further propose that the decorative elements associated with the stem coalesce to form the two outer-arm "feet" seen in situ, and that at least one of the in vitro stalks is equivalent to the in situ stalk, which extends from the head to the B microtubule. Deep-etch images of stretched axonemes, partially extracted axonemes, and dynein-decorated brain microtubules indicate that each outer arm, as traditionally viewed, is a hybrid of two dynein molecules: its two feet derive from one molecule, whereas its trigonal head derives from the molecule located distally. The resultant overlapping configuration creates the diagonal "linkers" seen in situ, which correspond to the in vitro stems. Thus, a row of dynein arms is essentially a dynein polymer that extends from the tip to the base of a doublet microtubule, each head riding on its neighbor's feet like a row of circus elephants.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 6241264 TI - Mutations that alter the DNA binding site for the bacteriophage lambda cII protein and affect the translation efficiency of the cII gene. AB - The efficiency of translation of the cII gene of bacteriophage lambda is greatly reduced by the cII3059 mutation, a GUU----GAU (Val----Asp) change in the second cII codon. Mutations in the third and fourth codons of the cII gene, called ctr mutations, reverse this translation deficiency. Lambda cII3059 ctr-1, which has a GCA----ACA (Ala----Thr) change in the fourth cII codon, produces about half the normal level of cII activity in liquid cultures, and lambda cII3059 ctr-2 and lambda cII3059 ctr-3, which have identical CGT----CGC changes in the third codon, produce normal levels of cII activity in liquid culture. Since the cII protein of ctr-3 has the same primary sequence as that of lambda cII3059, the cII- phenotype of lambda cII3059 can be explained entirely by the deficiency of translating cII mRNA. We propose that ctr mutations increase translation efficiency by destabilizing a stable stem structure which can be formed by cII mRNA. The ctr mutations lie in an overlapping regulatory region which contains, in addition to sequence elements that influence the rate of cII translation, a region to which cII protein binds to activate transcription from the PRE promoter. The ctr-1 mutation alters the cII recognition sequence from 5'-T-T-G-C-N6T-T-G-C-3' to 5'-T T-G-C-N6T-T-G-T-3', but has no effect on PRE activity. Since a C----T change in the first (5'-proximal) T-T-G-C sequence (to yield 5'-T-T-G-T-N6T-T-G-C) greatly lowers cII binding affinity, cII protein must not recognize the two T-T-G-C sequences in an identical manner. PMID- 6241265 TI - Transcription-dependent localization of U1 and U2 small nuclear ribonucleoproteins at major sites of gene activity in polytene chromosomes. AB - The location and dynamics of small nuclear ribonucleoproteins (snRNPs) were studied in salivary gland polytene chromosomes of Chironomus tentans by immunofluorescence with specific snRNP antibodies. Monoclonal antibody against the snRNP Sm antigens reacted at all sites of transcription (puffs and Balbiani rings). The amount of snRNP immunofluorescence was strictly dependent on transcription, increasing in parallel with gene activation and decreasing upon repression. Identical patterns of localization and transcriptional dependence were observed with antibodies specific for U1 or U2 snRNPs. These latter results show that the involvement of U1 and U2 snRNPs in transcription-related processes involves a high proportion, rather than small subsets, of active gene loci. In addition, the colocalization of U1 and U2 snRNPs at loci known to contain only one messenger RNA transcription unit (e.g. Balbiani ring 2) raises the possibility that both of these snRNPs interact with the same transcript. Finally, the lack of immunofluorescence at repressed loci indicates that snRNPs are not structural components of the chromatin (DNP) fiber, and also shows that unused snRNPs are not stored in chromatin. These latter points, and the growing evidence for the involvement of U1 snRNP in splicing, suggest that nascent pre-mRNA is the major chromosomal binding site for snRNPs. PMID- 6241266 TI - Effects of metal-containing drugs taken simultaneously with clioquinol upon clinical features of SMON. AB - In order to explore the effects of metals upon the subsequent onset of several clinical events in SMON, a retrospective cohort study was attempted. Study subjects were 216 "exposed" patients and 149 "unexposed" patients. "Exposure" was defined as the simultaneous ingestion of metal-containing drugs with clioquinol before the onset of neurological disorders. These two cohorts were identified from 531 patients among 832 patients, collected by the nationwide survey in 1975 and 1976. Effects provoked by ingestion of five metals (alminum, calcium, magnesium, copper and bismuth) were evaluated by relative risks with and without adjustment of the total amount of clioquinol ingested. Adjusted relative risks were estimated by maximum likelihood method. Significance of relative risk was determined by its 95% confidence interval. Following major findings emerged from the present analysis. (1) Simultaneous ingestion of Al-, Ca-, Mg-, Cu- or Bi containing drugs with clioquinol significantly reduced the risk of developing motor disturbances. (2) Risk of developing visual disturbances were favorably modified by Al-containing drugs. (3) Clinical severity was significantly reduced by ingestion of Al-, Ca-, Mg- or Bi-containing drugs. (4) About 2-fold increase in risk of unfavorable clinical course was demonstrated by Al-containing drugs. (5) Onset of both green-fur on the tongue and relapse appeared unrelated to the metal-containing drugs ingested. (6) Combined ingestion of two kinds of metal containing drugs with clioquinol appeared to yield more favorable effects than single ingestion of metal-containing drugs. (7) Al- or Bi-containing drugs demonstrated the strongest association with clinical features of SMON, followed by the drugs containing Mg or Ca. Cu-containing drugs had little association. PMID- 6241268 TI - [Scintigraphic investigation of the clavicular bone area in patients with psoriasis]. PMID- 6241267 TI - Inhibition of glucose reabsorption induced by 6-aminonicotinamide in the rat kidney. AB - The relationship between natriuresis and glucosuria produced by administration of 6-aminonicotinamide (6-AN), was investigated in the rat. After intraperitoneal administration of 6-AN (75 mg/kg), urine was collected at intervals of 2 hours using a metabolic cage for assays. Sodium and glucose were excreted maximally into the urine at 2 to 4 and at 4 to 6 hours, respectively, after the administration of 6-AN, with a time delay being recognized between sodium and glucose in the peaks of their urinary excretions. This dissociation of the patterns on the urinary excretion between sodium and glucose led to the following conclusion that the natridiuresis induced by 6-AN was not mainly ascribed to the osmotic diuresis for glucose, but to the direct effect on the sodium transport in the kidney. Furthermore, additional experiments were carried out by loading animals with glucose after administration of 6-AN. The tolerance for glucose in the body was clearly depressed in rats in the 6-AN group, while no significant difference in the renal threshold concentration for glucose was shown in either group. The renal tubular transport maximum for glucose was also depressed in the 6-AN group. It is, accordingly, speculated that the glucosuria induced by 6-AN was not only due to the hyperglycemia, but also due to the decreased capacity of the renal tubular reabsorption for glucose. PMID- 6241269 TI - Inhibitory effect of 6-aminonicotinamide on the renal transport of para aminohippurate in the rat. AB - In this study, we investigated the effect of 6-aminonicotinamide (6-AN), a typical potent inhibitor of the pentose phosphate pathway, on the renal transport of para-aminohippurate (PAH) in the rat. The contents of adenosine-triphosphate (ATP) and 6-phosphogluconate (6-PG) in the kidney were measured at intervals of 2 hours after the administration of 6-AN (75 mg/kg body weight, i.p.). It was found that the 6-PG content in the kidney rapidly increased and reached a plateau at the fourth hour after the administration, with this level being maintained up to the eighth hour. In contrast, the ATP content was found to remain normal up to the sixth hour, after which it significantly decreased as time elapsed. Furthermore, additional experiments were carried out by loading the rat with a high concentration of PAH solution at 6 hours after the administration of 6-AN. The renal tubular secretion maximum for PAH was significantly depressed in the 6 AN group in comparison to the control. These results suggest that this depression in renal PAH secretion capacity was partially due to the inhibition of the pentose phosphate pathway in the kidney, but not due to the change of renal ATP level. PMID- 6241270 TI - [Selected problems of surgical treatment of ischemic heart disease]. PMID- 6241271 TI - Analysis of immune status of hemodialyzed adults: association with prior transfusions. AB - Peripheral blood leukocytes of 29 hemodialyzed adults, 19 transfused and 10 nontransfused, were studied using immunofluorescent staining with monoclonal antibodies and in vitro measurement of natural killer (NK) cell activity. When compared with control subjects, the absolute number of leukocytes in transfused hemodialyzed patients was significantly reduced (P less than 0.01), as were the absolute numbers of OKT11+ cells (P less than 0.01), and OKT4+ cells (P less than 0.0001). The percent representation of OKT11+ and OKT4+ cells was also significantly lower among transfused hemodialyzed patients (P less than 0.01 and 0.001, respectively), and this loss of OKT4+ cells resulted in a decrease in the ratio of OKT4+/OKT8+ cells (P less than 0.01). The absolute number of Leu-7+ cells was also decreased in the transfused group (P less than 0.05). A decrease in in vitro NK cell activity was present in both transfused and nontransfused hemodialyzed subjects. Whether these differences in peripheral blood lymphocytes were induced by the erythrocyte transfusions could not be determined; however, if they reflect changes in central lymphoid tissues, then these results may help explain the prolonged survival of renal allografts in transfused individuals. PMID- 6241272 TI - Evidences that endogenous 5-hydroxytryptamine participates in the contractile response to morphine in the rat isolated colon. PMID- 6241273 TI - [Value of a relaxing incision and compensation of the aponeurotic defect with ampoxen in an operation for hernia]. PMID- 6241274 TI - Sensitivity of pathway rate to activities of substrate-cycle enzymes: application to gluconeogenesis and glycolysis. AB - In a study of metabolic regulation, it is frequently useful to consider the degree to which an enzyme can influence the rate of its pathway. The most productive expression of rate-controlling influence is the fractional change in pathway rate per fractional change in enzyme activity (called control strength or sensitivity coefficient). We have developed a system for considering how a substrate-cycle enzyme's control strength depends on its flux and reaction order and on related features of other enzymes of its pathway. We have applied this system to the gluconeogenic pathway of rat liver and the glycolytic pathway of bovine sperm, where enough fluxes and reaction orders have been published to allow valid estimates of several control strengths. In normal fed animals where gluconeogenesis is slow and unidirectional substrate-to-product and product-to substrate fluxes are comparable, all substrate-cycle limbs have very high and similar control strengths regardless of their flux rates and positions in the pathway. The activity of a step affects all substrate-cycle control strengths similarly as it affects unidirectional end-to-end fluxes relative to net rate. Control strengths of non-substrate-cycle enzymes are negligible compared to those of substrate cycles. In fasting animals, on the other hand, where unidirectional Pyr----Glc flux is much greater than Glc----Pyr flux, upstream enzymes (near Pyr) have a regulatory advantage over downstream enzymes (near Glc). In this circumstance, control strength of each substrate-cycle enzyme is inversely related to rate limitingness between its substrate and the pathway substrate. Because the Pyr/PEP cycle is significantly rate limiting, the control strength of the Pyr----PEP limb is much greater than that of pyruvate kinase and all downstream enzymes. In the glycolytic pathway of bovine sperm, strong product inhibition of hexokinase detracts greatly from its rate limitingness and control strength, which are very small despite its position at the beginning of the pathway and its large free energy. Because the glucose-transport-hexokinase segment is not rate limiting, phosphofructo 1-kinase has almost as much control strength as it would have as the first enzyme of the pathway, and because the F6P/FDP cycle is only moderately rate limiting, Fru-1,6-P2ase and enzymes further downstream have substantial control strengths. When glycolysis is accelerated by stimulation of phosphofructo 1-kinase, control strength shifts from phosphofructo 1-kinase and all downstream enzymes to the transporthesokinase segment.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 6241275 TI - Adsorption of peripheral enzymes to membrane anchor proteins. AB - The character of the isotherms of specific adsorption of peripheral enzymes to dimeric anchor proteins embedded in the membrane has been analysed. The situations are discussed when adsorption corresponds to the stoichiometry of one or two molecules of peripheral enzyme per dimeric binding site. The corresponding expressions describing the competitive interrelationships between peripheral enzymes adsorbed to the same binding sites have been derived. The experimental data on the adsorption of glycolytic enzymes to erythrocyte membranes are used for the illustration of the theoretical predictions. The physiological role of enzyme self-association which leads to the formation of enzyme oligomers of unlimited length is discussed. It is assumed that under in vivo conditions the association sites of such enzymes are saturated through interactions with anchor proteins of subcellular structures and with the enzymes of the corresponding metabolic pathways. Therefore the linearly associating enzymes play the key role in the formation of multienzyme complexes attached to subcellular structures. The significance of 6-phosphofructokinase adsorption to erythrocyte membranes in the formation of the complex of glycolytic enzymes is discussed. PMID- 6241276 TI - [Dermatitis caused by mexiletine]. PMID- 6241277 TI - [Idiopathic hypogammaglobulinemia of late appearance: a T-lymphocytes disease?]. PMID- 6241278 TI - [Keratosis palmaris and visceral cancer]. AB - The authors describe the clinical and histological characteristics of palmar keratose associated to visceral cancer. Their clinical forms are small and numerous keratotic rings, large papulae, 4 to 8 mm., scarce two or three lesions and multiple punctiform depressions. The histology shows a compact orthokeratotic hiperkeratosis accompanied in a variable way to an epidermic depression. In a strict sense it is not a paraneoplase, it is a clinic visceral cancer marker. It is suggested to name it oncogenic lenticular acrokeratose. PMID- 6241279 TI - [Nickel sensitivity in an atopic patient]. AB - A case of atopic dermatitis with it's classics signs in face and extremities, with an eight years evolution is reported. It was treated with corticoids (local and systemic) with no favorable results. In the allergic investigation it was found a sensibilization to nickel. She was cured by eliminating the nickel from her diet and from the objects in contact. Clinic and etiopathogenic considerations between allergic dermatitis by contact to nickel in the atopic and the non-atopic are made. PMID- 6241280 TI - Activation of polyunsaturated fatty acids by rat tissues in vitro. AB - The conversion of labeled palmitic, linoleic, arachidonic and docosahexaenoic acids to their respective acyl CoA's was studied in homogenates and microsomes of rat tissues. The highest activity, both in homogenates and microsomes, was seen in liver and heart. There was moderate activity in retina, brain, lung, kidney and testes and the lowest activity was found in spleen. Docosahexaenoic acid was activated much less actively in heart tissue than the other fatty acids. In all tissues examined, the highest activation was observed with arachidonic acid and the lowest with docosahexaenoic acid. Except for liver, those tissues that contained high levels of docosahexaenoic acid also had the highest activation capacity for this fatty acid. PMID- 6241282 TI - [Training is the main thing in the work of paramedical personnel]. PMID- 6241281 TI - [Nursing care for premature infants in the polyclinic]. PMID- 6241283 TI - [Album of the activities of a council of paramedical workers]. PMID- 6241284 TI - [Training of paramedical personnel in the specialty of instructor of therapeutic physical exercise]. PMID- 6241285 TI - [Assessment of student work in medical colleges]. PMID- 6241286 TI - Cell separation on cellular monolayers. PMID- 6241287 TI - Suicide of lymphoid cells. PMID- 6241288 TI - Multiple genes control particulate phosphofructokinase of yeast. AB - Mutants of Saccharomyces cerevisiae lacking the particulate phosphofructokinase define at least four unlinked genes, PFK2, PFK3, PFK4 and PFK5. A structural role of PFK2 is indicated. Mutations in the other three have pleiotropic effects. PMID- 6241289 TI - Alzheimer's disease and malnutrition: a new etiological hypothesis. AB - The author proposes an etiological hypothesis for Alzheimer's disease (malnutrition with or without malabsorption); this may explain clinical and biological phenomena which occur in this disease. A search through the literature revealed that all people suffering from Down's syndrome (and who all develop Alzheimer's disease from forty years of age) also suffer from malnutrition. This hypothesis may explain the anatomical and neurobiochemical perturbations and the inefficacy of choline. Consequent nutritional treatment of the disease is proposed. PMID- 6241290 TI - Hodgkin's disease: five steps from autoimmunity to cancer. AB - A five-step hypothesis on the pathogenesis of Hodgkin's disease (HD) is presented. Weak immune suppressor activity gives a predisposition for the development of the disease, after which a non-specific immune stimulation can initiate a self-perpetuating uncontrolled stimulation between interdigitating cells (IDCs), macrophages and helper T lymphocytes (TH). The disease spreads to other lymph nodes through the secretion of humoral factors and by migration of cells. The response of the suppressor branch of the immune system is delayed, and comes from areas not yet involved in the disease, primarily from the spleen and bone marrow. Treatment will result in the predominance of the suppressor activity and allow calming of the disease. In a terminal phase, a possible neoplastic transformation of the chronically stimulated immune cells may give rise to frequent extranodal localizations and a rapid progression of the disease. PMID- 6241291 TI - [Allergic diseases in the cosmetics industry]. PMID- 6241292 TI - Lack of spontaneous and inducible natural killer cell activity in human bone marrow: presence of adherent suppressor cells. AB - Human bone marrow cells collected from ribs of patients undergoing thoracotomy had low or no natural killer (NK) cell activity against K562 in a 4-hour chromium release assay. In vitro overnight treatment with interferon or interleukin 2 of bone marrow cells resulted in no induction or augmentation of NK cell activity. In the presence of adherent bone marrow cells interferon was unable to enhance NK cell activity of blood lymphocytes, although the baseline level of NK cell activity was not suppressed. These results suggest that adherent bone marrow cells regulate the development of active NK cells and that bone marrow components do not provide a favorable environment for the functional differentiation of NK cells. PMID- 6241294 TI - Late Dacron graft failure: two cases. PMID- 6241293 TI - Systemic administration of human leukocyte interferon to melanoma patients. III. Increased helper:suppressor cell ratios in melanoma patients during interferon treatment. AB - Malignant melanoma patients treated with human leukocyte interferon (IFN-alpha) displayed increased natural killer (NK) cytotoxicity to K562 targets within the first 2 weeks of therapy. This study explored the possibility of T-cell regulation of this NK response, as evidenced by a variation in T-cell subpopulations. T-cell subset levels were studied in 9 patients who received daily doses of IFN-alpha over a period of 42 days. Five monoclonal antibodies to T-cell surface markers were used: Leu 1 (pan-T), Leu 2a (T suppressor/cytotoxic), Leu 3a (T helper/inducer), HNK-1 (Leu 7, a marker for NK cells), and B73.1 (an antibody against the Fc receptor on NK/K cells). Percentages of these markers were measured on days 0, 3, 7, and 21 of treatment. Percentages of Leu 1-positive cells and Fc-receptor-positive cells remained relatively constant throughout treatment in all patients. A trend toward a decrease in suppressor cells and an increase in helper cells peaking on day 7 and returning to earlier values by day 21 was found in 5 patients. The increase in NK cytotoxicity was not reflected consistently in proportions of HNK-1-positive cells or Fc receptor-bearing cells within the first week of therapy. The most significant finding was an increase in the helper:suppressor cell ratio peaking on day 7 and returning to pretreatment values by day 21. This increase was seen in every patient studied. The average pretreatment Leu 3a:Leu 2a ratio was 0.67 increasing to an average value of 1.47 on day 7 (p less than 0.005). Leu 3a:Leu 2a ratios returned to pretreatment values, in parallel to NK activity, despite continuation of interferon therapy. PMID- 6241295 TI - Regulation of phosphofructokinase in rat submandibular gland. PMID- 6241296 TI - [The dental anamnesis of patients with somatic fixation]. PMID- 6241297 TI - [Lumbosciatica caused by spondylolisthesis. Results of the surgical treatment by facetolaminectomy and interbody arthrodesis by the posterior approach in a series of 66 cases]. AB - 66 patients with spondylolisthesis were reviewed after surgical procedure with a follow-up period of more than a year postoperatively. The indication for the operation was disabling sciatica in all patients. 4 patients had undergone prior excision of the herniated disc. All the patients underwent a removal of the loose posterior element as suggested by the Gill procedure and intervertebral body fusion using a posterior surgical approach. The surgical procedures with only one regressive neurological complication are described. The results are considered from a clinical and anatomo-radiological point of view. In this series 86.5 percent of 66 patients became sciatica-free. 62 percent of the total series rated the end result as excellent or good. 92.4 percent of the patients demonstrated bony fusion between the two grafted vertebrae. The benefits of posterior laminectomy with interbody fusion are also attractive for spondylolisthesis with sciatica. PMID- 6241298 TI - [Questionnaire method of evaluating the effectiveness of the treatment of pain]. AB - A Polish version of pain questionnaire for pain intensity definition has been prepared after an inquiry study on the "pain glossary" which showed that in the Polish language a large number of words are used for characterization of pain. These words contain information about pain intensity understandable for the studied population. The authors describe this questionnaire and discuss a preliminary evaluation of its usefulness for assessing the effectiveness of pain management. The presented questionnaire makes possible evaluation of pain intensity in several indices whose values correlate significantly with each other. In comparative investigations a significant correlation has been found also between the indices of pain intensity in the questionnaire and the index in the 24-hour observation card. The mean differences of pain intensity scores calculated before and after the treatment differed significantly in definite categories of verbal evaluation of treatment effectiveness. This justifies the conclusion that the questionnaire may be useful for evaluating treatment effectiveness by a method not depending on the utterances of the patients. PMID- 6241299 TI - Effect of some serotoninergic agents on the rectal temperature of the domestic fowl (Gallus domesticus). AB - The information currently available in the literature on the effects of serotonergic drugs on thermoregulation in the avian species is very scanty. Therefore, it was the objective in this project to study the influence of 5 hydroxytryptamine (5-HT), 5-hydroxytryptophan (5-HTP), benserazide, carbidopa (Mk 486), citalopram, cyproheptadine, methysergide, xylamidine, p-chlorophenylalanine (PCPA) and lysergic acid diethylamide (LSD-25) on the rectal temperature of young chicks. 5-hydroxytryptamine (0.8 mg/kg), produced significant dose-dependent hypothermia in young chicks. Similarly, 5-HTP (16 mg/kg) profoundly lowered the rectal temperature of young chicks. The hypothermic effect of 5-HTP was potentiated by benserazide (1.25-2.5 mg/kg). Pretreatment with carbidopa (50 mg/kg) potentiated 5-HTP induced hypothermia. Citalopram (5 mg/kg) significantly potentiated hypothermia induced by 5-HT. Pretreatment with PCPA (200 mg/kg, 24 hr previously) alone resulted in hyperthermia while the hypothermic effect of 5-HTP (16 mg/kg) was antagonised by pretreatment with PCPA. Cyproheptadine (1.25 mg/kg) antagonised the hypothermic effect of 5-HT (0.1 and 0.8 mg/kg). The antagonistic effect was weak when the chicks were pretreated with larger doses of cyproheptadine (i.e. 2.5-10 mg/kg). The hypothermia induced by 5-HT (0.8 mg/kg) was antagonised by smaller doses of methysergide (0.125-1.0 mg/kg) but potentiated by larger doses of methysergide (2.0 and 4.0 mg/kg). Xylamidine (1-2 mg/kg) alone induced hyperthermia and effectively antagonised hypothermia induced by 5-HT (0.8 mg/kg). D-Lysergic acid diethylamide (2.5-10 micrograms/kg) alone induced hypothermia. The interaction between LSD and 5-HT was dose-dependent and biphasic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 6241300 TI - Striatal dopamine receptors in Alzheimer-type dementia. AB - Dopamine D1 and D2 receptors were studied in putamen of post-mortem brains from controls and patients with Alzheimer-type dementia (ATD). A significant reduction in dopamine D2 receptors was observed in ATD, whereas dopamine D1 receptors were unchanged. Neurochemical markers of striatal acetylcholine and GABA-containing neurones were also within the normal range. The results are consistent with a loss of D2 receptors located on cortico-striatal neurones in putamen of some ATD patients. In contrast, markers of intrinsic neurones may remain unchanged. PMID- 6241301 TI - The disabled and living--starting a new life. PMID- 6241302 TI - [Therapy effect of intrathecal, nerve stem and pain pressure point electroacupuncture in severe refractory back and leg pains]. PMID- 6241303 TI - [Preventing the spread of hepatitis B infection during dental treatment]. PMID- 6241305 TI - [Organization of rehabilitation treatment of traumatologic patients]. PMID- 6241304 TI - [Prognostic value of serum CEA and therapy-induced nonspecific CEA levels in metastasizing breast carcinoma]. AB - In 57 patients with metastasized breast carcinoma, serum CEA levels (CEA-Ria-Kit, Abbot) were correlated with the clinical course under endocrine or cytostatic therapy. In 20 patients, CEA was determined at intervals of 1 to 3 days over the first 4 weeks of treatment and in 21 patients at intervals of 1-3 weeks. In 16 patients, CEA was determined prior to treatment. The clinical development was judged according to the program of UICC. We found pretreatment CEA values higher than 25 ng/ml serum mostly in patients with liver involvement and in patients with progression under the following therapy. In 22 patients, progress or remission of the disease were correlated with CEA increase or decrease of more than 20% during the first 8 weeks. In 11 patients, we found no correlation between CEA and clinical course. From the remaining 8 cases, CEA levels were out of the measuring range in 6 patients, in 2 patients we were unable to interpret the clinical course doubtlessly. There were no short-termed CEA alternations after the start of the treatment rendering a possible early estimation of the therapy effect. In 5 of 23 patients treated with methylprogesteronacetate and aminoglutethimide a continuous CEA increase developed despite clinical remission. This was not found in 10 patients treated with cytostatic chemotherapy. The pretreatment CEA is a useful prognostic parameter in patients with metastasizing breast cancer. CEA should be determined weekly in patients with increasing CEA levels under therapy and monthly in patients with decreasing CEA levels. The possibility of a tumor-independent CEA rise as a side-effect of treatment must be taken into consideration. PMID- 6241306 TI - [Dentin adhesive resins: new application and clinical results in conservative therapy (1: Cavex Clearfil adhesive resin)]. PMID- 6241307 TI - [Heredity and atrophic dystrophic periodontal diseases]. PMID- 6241308 TI - [Current aspects of laparoschisis. Apropos of 22 cases]. AB - Study about 22 gastroschisis observed 17 years along allows to the authors to point out the elements of amelioration of prognostic and decrease of mortality. Antenatal diagnosis allows the hysterotomy at the end of gestation avoiding traumatic or infectious risks. Reanimation and transport are very important to bring the neonate in good conditions to the pediatric surgeon. The choice of surgical technics is only between primitive parietal closure or progressive reintegration (Schuster). Intestinal atresia must be cured in the same time, if possible. Finally, perisurgical nursing, antibiotherapy and recent parenteral nutrition method improved the prognosis. During the last 15 years, mortality has fallen from 80% to 10%. PMID- 6241309 TI - Effects of changes in preoptic temperature on stretch response of muscle spindle endings in the cat's soleus muscle. AB - The effects of changing the temperature in the preoptic region on the stretch responses of primary and secondary endings of the muscle spindle in the soleus muscle was investigated in urethane anesthetized cats. The local temperature of the preoptic region was controlled by implanting water perfused thermodes (32 42.5 degrees C). A standard ramp and hold stretch stimulus was repeatedly applied to the soleus muscle during changes of preoptic temperature from normal to hypo- or hyperthermic values. During each stretch the instantaneous firing rate was recorded and the static firing frequency and the dynamic index were electronically determined according to Crowe and Matthews (1964). Of a total of 76 investigated muscle spindle afferents, the stretch responses of 49 (65%) were altered by changing preoptic temperature. The static stretch response was increased in all cases during cooling, whereas during preoptic heating the static stretch response increased in about half of the afferents and decreased in the rest. Increase in the static stretch response during both cooling and heating was usually combined with the appearance of spontaneous discharges at rest. With regard to the static stretch response, primary and secondary muscle spindle endings responded similarly to cooling and heating. Two types of preoptic temperature effects on the stretch responses of primary endings were observed. In the majority of afferents only the static stretch response was augmented during cooling, whereas the peak response was little changed resulting in a decrease of the dynamic index ('static' response type).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 6241310 TI - [Sodium content of erythrocytes in patients with arterial hypertension and in healthy persons]. PMID- 6241311 TI - [Electrocardiographic diagnosis of left-ventricular hypertrophy in arterial hypertension]. PMID- 6241312 TI - [Efficacy of a controlled program of oral hygiene in a group of handicapped patients: preliminary report]. PMID- 6241313 TI - Down's syndrome and Alzheimer's dementia: defining an association. AB - The typical neuropathological features of Alzheimer's disease, plaques and tangles, appear in virtually all patients with Down's Syndrome after the age of 40. Clinically, changes in cognitive performance and behavior appear to correlate with these neuropathological changes, although a satisfactory operational definition of dementia in a context of mental retardation is not available. It is unknown whether the cholinergic losses in the nucleus basalis, which are a feature of early onset Alzheimer's disease, also occur late in Down's syndrome. Two family studies have supported a greater than expected incidence of Down's cases among relatives of probands dying with Alzheimer-type dementia, but the association is not strong. It is noteworthy that in both studies, phenotypically normal carriers of the rare 15/21 translocation had severe early onset dementia, although this translocation is responsible for less than 0.4 per cent of Down's cases. An increased incidence of dementia among carriers of the more common 14/21 translocation has not been reported. In any case, it is proposed that a gene product originating from the long arm of chromosome 21 (21q) is necessary for Alzheimer-type pathology, since a segregating gene could not be responsible for the 100 per cent incidence of these changes among 21q trisomics. PMID- 6241315 TI - Epilepsy and its prejudice. Teachers' knowledge and opinions: are they a response to psychopathological phenomena? AB - 150 teachers, 75 from a group of basic schools and 75 from a group of schools on an advanced level were asked to respond to a questionnaire consisting of 194 items in order to find out about their actual state of knowledge, opinions and prejudices against epileptics. 45 stereotype statements had to be rated for 'epilepsy', 'insanity', and 'heart disease'. A ranking order of 6 disorders- 'insanity', 'depression', 'epilepsy', 'heart disease', 'amputation of a leg', and 'diabetes mellitus' had to be established. Teachers' knowledge of epilepsy proved to be somewhat diffuse but in good keeping with reality and they showed an interest in more information and research. Some of their prejudices could be attributed to old ideologies while the acquaintance with epileptics enhanced their knowledge of their real needs. Teachers' confusions went along with the controversies in medical research. PMID- 6241316 TI - [Early benefits to handicapped children from the dentist? A new aspect of dentistry]. PMID- 6241314 TI - Role of serotonin in memory: facilitation by alaproclate and zimeldine. AB - The effects of alaproclate and zimeldine on memory retrieval were examined in male Swiss-Webster mice using a one-trial inhibitory avoidance task. All drugs were administered IP prior to the retention test 24 h after training. Both drugs were found to facilitate memory retrieval significantly in a dose- and time dependent fashion that could not be explained in terms of non-specific effects of the drug (illness, lack of motility, etc.) at the time of the test. The temporal effects of alaproclate and zimeldine on memory closely followed their course of concentration of the drug within the blood stream. The facilitation of retrieval induced by alaproclate and zimeldine was blocked by the putative serotonergic receptor agonist quipazine but not blocked by the antagonist cyproheptadine. Pretreatment with quipazine alone in a group of animals trained to a shock level which normally results in high levels of suppression was not sufficient to produce memory impairment, suggesting that quipazine was probably antagonizing the facilitative effects of alaproclate and zimeldine directly, rather than overriding the facilitation through an indirect action on retrieval in general. The present results lend further support to the suggestion that serotonin plays a significant role in memory. PMID- 6241317 TI - Serotoninergic influences on sexual differentiation of the rat brain. PMID- 6241319 TI - [Dopamine receptors]. PMID- 6241318 TI - Hormonal organization of sex differences in play fighting and spatial behavior. PMID- 6241320 TI - [Nickel hypersensitivity]. PMID- 6241322 TI - [Biochemistry of glaucoma and cataract. A documentary study]. PMID- 6241321 TI - [Spectinomycin in the treatment of complications of gonorrhea in men]. PMID- 6241323 TI - [Heredity in strabismus]. PMID- 6241324 TI - [Practical considerations of peripheral inflammation of the fundus oculi]. PMID- 6241325 TI - [Use of Healon in ophthalmologic surgery]. PMID- 6241326 TI - [Treatment of macular holes]. PMID- 6241327 TI - [Early results following trabeculectomy at the Cluj-Napoca Ophthalmological Clinic]. PMID- 6241328 TI - [Photic injury to the retina in eye surgery]. PMID- 6241329 TI - [Combination of surgical procedures in treating retinal detachment--the results]. PMID- 6241330 TI - [Sphenoidal meningioma invading the orbit]. PMID- 6241331 TI - [Tolosa-Hunt syndrome]. PMID- 6241332 TI - [Microradiographic aspects of massive bone allografts in man]. AB - Two stored frozen massive bone allografts were implanted after resection of femoral and tibial tumours in two patients. Eighteen and thirty months later the authors had the opportunity to make a microscopic examination of the grafts. The cortical bone grafts were incorporated by the classic "creeping substitution." The repair of the cortical transplant was very incomplete and showed large resorption cavities. The newly-formed living bone was not fully mineralized. These phenomena related only to the outer area of the cortical bone, the dead intra-cortical area being left unaffected by the process. Cancellous bone graft repair was faster and more efficient. PMID- 6241333 TI - [Bone and skin vascularization of the lower 4th of the leg]. AB - The authors have studied the vascular network of bone and skin in the lower third of the leg by injection of methyl methacrylate in 31 cadavers. The vascular supply of the bone is given by metaphyseal and epiphyseal arteries branching from the main trunks. Different types of vascular network are described. The vascular supply of the skin is given by a subaponeurotic plexus with branches crossing in areas which can be considered as radiating vascular hili. These hili should be preserved during surgical operations. Conclusions are given concerning the security of the surgical approaches at the lower third of the leg. PMID- 6241334 TI - [Chiari's osteotomy. Difficulties in the realization of biomechanical goals. Apropos of 32 operations]. AB - The authors have made an anatomical study on cadavers to determine more precisely the mechanical goal of Chiari osteotomy and its achievement. They note that the procedure aims to improve the lateral and anterior coverage of the femoral head, to suppress subluxating forces and to medialize the hip to decrease the tension of the gluteus medius. The line of osteotomy must allow rotation of the lower fragment of the iliac bone beneath the upper part, the axis of rotation being the symphysis pubis. The ideal line of osteotomy should be conical and as vertical as possible but leaving the sacro iliac joint unimpaired. Its achievement is made easier by a pre-operative drawing in which the following points should be respected. The sagittal displacement should be calculated on a true antero posterior radiograph in which the direction of the axis of the pubic symphysis can be appreciated. The correct position of the guide pins should be determined by the location of its point of entry and exit and not by its obliquity which may be misleading. Medialization should be obtained by abduction of the thigh and not by pressure on the greater trochanter to avoid total pelvic translation. Thirty eight patients have been operated on and followed up for more than one year. Twenty one results were satisfactory. PMID- 6241335 TI - [Postero-internal menisco-capsular disinsertions associated with chronic instabilities of the knee caused by rupture of the anterior cruciate ligament]. AB - Posterior menisco-capsular tears of the medial compartment of the knee can be considered as a complication of rupture of the anterior cruciate ligament and the consequent medial instability. The lesion is more a capsular lesion than a true meniscal one and it is related to an excessive stress on the oblique fibres of the ligament of Hughston attached to the meniscus. The diagnosis is based on arthrography made with meticulous technique. The lesion must be differentiated from true meniscal tears because it can be sutured. One hundred and twenty five such lesions have been operated on and reviewed after a follow-up of an average of two years. The technique must be very precise to prevent any secondary lesion due to surgery and to avoid any plaster cast immobilisation. The results have been satisfactory in 69 p. 100. They should be improved with more accurate surgical technique and with more precise indications. PMID- 6241336 TI - [Extensive excision of the upper end of the femur in children with motor handicap of cerebral origin]. AB - The authors have resected the upper part of the femur on 17 occasions in 12 teenagers suffering from spastic paraplegia or quadriplegia. The patient had no hope whatsoever of walking. The hips were dislocated and painful. This type of procedure is justified by failure of other procedures aiming to stabilise the hips in spastic patients. It was performed by a double approach-anterior and posterolateral. The quality of post-operative care is very important. After an average follow-up of 3 years the results were satisfactory in 8 patients. Three had post-operative complications of pain, increased spasticity and secondary fracture of the femur. The indications must be considered because secondary bone formation may take place and decrease the quality of the result. The main goal is to diminish pain and increase comfort. PMID- 6241337 TI - [An unknown after surgical lengthening of the femur in children: spontaneous postoperative parasitic lengthening]. AB - The authors have studied overgrowth or diminished growth seen in 54 femora lengthened surgically by a one-stage procedure between 1963 and 1979. Thirty six cases were of poliomyelitis. An overgrowth was regularly seen of the order of 2.5 p. 100- that is 11 mm on average. This stimulation of growth by lengthening was not related to age. It was more marked where there was severe involvement. In contrast, in 13 cases of congenital femoral abnormalities and 5 cases of miscellaneous diseases (Ollier's disease, neurofibromatosis, sequelae of septic arthritis) overgrowth or diminished growth have been observed. This phenomenon was not constant and could not be predicted. PMID- 6241338 TI - [Surgery in failure of nucleolysis of lumbar disk hernia]. AB - The authors have reviewed 206 cases of sciatica treated by Chemonucleolysis. Thirty-two had to be operated on later. This treatment was more frequently needed at L4/L5 level than at the lumbosacral level. Most of the failures of Chemonucleolysis were related to lateral spinal stenosis (13 cases). In 4 cases it was due to disc extrusion either at the time of the Chemonucleolysis (2 cases) or appearing later (2 cases). Nine failures were due to subligamentous disc herniation. Two cases were operated on for the onset of sciatica at another level, repeated treatment with Chemonucleolysis being contra-indicated. In 3 cases, the surgical exploration did not discover the cause of the sciatica. The surgical cases were not impeded by the preceding Chemonucleolysis and no adhesions were found. The results were similar to those observed after primary surgery - about two-thirds of satisfactory results. They were better when a herniation at another level was found or in cases of disc extrusion than in cases of spinal cord stenosis or sub-ligamentous herniae. They were poor when the cause of the sciatica was not found. PMID- 6241339 TI - [Irreducible closed luxation of the distal interphalangeal joint. Apropos of 2 cases]. AB - Two irreducible dislocations of the distal digital interphalangeal joint have been seen by the author. One was dorsally displaced with interposition of the extensor tendon, and the other was a palmar displacement with interposition of the flexor tendon. Both cases were successfully treated by open reduction. A review of the literature confirms the rarity of this condition. PMID- 6241340 TI - [Ligamentoplasty using the peroneus brevis in the treatment of chronic instabilities of the ankle. Long-term review]. AB - Sixteen cases in which a ligamentoplasty using the peroneus brevis have been followed up for more than 8 years. In half of the cases dorsi-flexion of the ankle was diminished and the subtaloid joint was stiff. There was no anterior drawer sign of the talus. No case of progressive degenerative arthritis of the ankle joint was seen. PMID- 6241341 TI - Adverse health effects and exposure to polychlorinated biphenyls. PMID- 6241342 TI - Signaling of ankle joint position by receptors in different muscles. AB - Plots were made of multiunit activity versus ankle joint position for receptors in each of the 12 muscles crossing the cat ankle joint, except peroneus tertius, by recording from populations of afferent fibers in muscle nerves. The discharge was measured 15 or 30 sec after terminating the movements that altered the position of the joint. These recordings were dominated by large-spike activity that would be expected to originate mainly from primary spindle endings. Seven of the 12 muscles also cross other joints. Their responses at a given ankle joint position were so altered by changes in the position of the knee or toe joints that they could not reliably signal the position of the ankle joint. As judged from multiunit recording, receptors in each of the five muscles specific to the ankle joint were influenced by more than one axis of ankle joint displacement. Single-unit recording from dorsal root filaments was used to determine whether primary or secondary spindle receptors in soleus and tibialis anterior could selectively signal one axis of ankle joint rotation. Individual soleus receptors were tested both on the flexion-extension axis and with a combined adduction eversion movement. For 38 of the 70 soleus receptors examined (54%), firm adduction-eversion produced a level of activity greater than that caused by 10 degrees of flexion, and for 77% the level of activity was greater than that caused by 5 degrees of flexion. For 168 of the 184 tibialis anterior receptors studied (91%), firm abduction-inversion produced a level of activity greater than that caused by 10 degrees of extension. Thus few receptors were found that responded exclusively to one axis of rotation. One way in which the position of the ankle joint could be specified in the face of multiaxial receptor activity is by examining the receptor discharge from more than one muscle. A suggestion for how the nervous system might do this is given in the discussion. PMID- 6241343 TI - [Technic of percutaneous transluminal angioplasty]. PMID- 6241344 TI - [Bases of percutaneous transluminal angioplasty and its mechanism of action]. PMID- 6241345 TI - [Indications and results of percutaneous transluminal angioplasty in arteriopathy of the extremities]. PMID- 6241346 TI - [Mid-term functional results of percutaneous transluminal angioplasty in arteriopathy of the lower extremities]. PMID- 6241347 TI - [Anatomo-radiological study and evaluation of percutaneous transluminal angioplasty in arteriopathy of the lower extremities]. PMID- 6241350 TI - [Dental service for the handicapped (5)]. PMID- 6241349 TI - [Dental services for the handicapped (4)]. PMID- 6241348 TI - Prevalence of cardiac and aortic enlargement in rheumatoid arthritis and its relationship to some characteristics of the patients. A radiological and clinical study. AB - The chest radiographs of 309 patients with rheumatoid arthritis (RA) were compared with those of 309 controls matched for sex and age. Cardiac enlargement was more frequent in RA females than in controls (P less than 0.05) and the frequency of aortic shadow enlargement was higher in RA patients aged greater than or equal to 60 years than in controls (P less than 0.05). Both cardiac and aortic enlargement was significantly related to several parameters of the severity and the activity of RA, corticosteroid therapy, and elevated blood pressure. A high mortality was present in patients with aortic enlargement and in patients with ECG signs of myocardial ischaemia. PMID- 6241351 TI - [Dental services for the handicapped (6)]. PMID- 6241352 TI - [Infrared rays for the management of occupational diseases of dentists and para dental staff]. PMID- 6241353 TI - [Oral examination of 1 1/2 -year-old infants]. PMID- 6241354 TI - [Caries activity tests]. PMID- 6241355 TI - [Dental care status in adult handicapped patients. A study in the Kristianstad district in 1983]. PMID- 6241356 TI - [Composite dental filling materials]. PMID- 6241357 TI - Quantitation of human protein S in the plasma of normal and warfarin-treated individuals by radioimmunoassay. AB - Protein S was purified from human plasma and used to raise monospecific antibodies. A double antibody equilibrium radioimmunoassay was constructed and met all the requirements for a sensitive, accurate and specific determination of Protein S. The sensitivity of the assay was between 8-250 ng of Protein S/ml and the coefficient of variation was 2-6% within assays and 13-19% between assays. Complement C4b-binding protein or Protein C did not effect the measurement of Protein S. Complete competition with parallel slopes of inhibition was seen among purified Protein S and plasma from normal and warfarin-treated individuals indicating immunochemical identity and validating the measurement of Protein S in plasma. The concentration of Protein S in normal plasma (n=24) was 23.4 +/- 4.42. micrograms/ml and in plasma from warfarin-treated individuals (n=24) was 12.6 +/- 3.92 micrograms/ml. Thus, a common feature of individuals undergoing warfarin therapy is the reduction of approximately 50% in the concentration of each of the vitamin K-dependent proteins. PMID- 6241358 TI - An autopsy case of Marfan syndrome with histochemical studies on the cardiovascular system. PMID- 6241359 TI - Significance of the delta 5 and delta 4 steroidogenic pathways in the hamster preovulatory follicle. AB - Isolated hamster granulosa cells and theca from preovulatory follicles were incubated in vitro for 2 and 6 h in the absence/or presence of LH and steroid substrates. The purpose of the experiments was to determine, in theca, the relative activities of the delta 5 and delta 4 pathways under controlled conditions, and to compare the ability of granulosa cells and theca to form progesterone from exogenous pregnenolone. The results of the experiments show that the delta 5 pathway in theca predominates before and up to 2 h after LH stimulation. The delayed effect of LH after 2 h is a switch from delta 5 to delta 4 as the major metabolic pathway. Progesterone formation from exogenous pregnenolone is 7 to 10 times greater in unstimulated granulosa cells than in theca. Acute effects of LH lead to increased conversion of exogenous pregnenolone to progesterone in granulosa cells but not theca. LH does, however, acutely stimulate the thecal conversion of DHEA to androstenedione. The longer term effect of LH in both cell types is to increase pregnenolone conversion to progesterone. PMID- 6241360 TI - An origin for the bone text of the 'five-figure series'. PMID- 6241361 TI - [New findings on the medicine of the Copts]. PMID- 6241362 TI - [G. B. Morgagni and his ideas on methodology in medicine]. PMID- 6241363 TI - [History of pneumonia]. PMID- 6241364 TI - Descartes' methodological transformation of Homo sapiens into Homo faber. PMID- 6241365 TI - [New knowledge on the problem of Paracelsus' Spuria]. PMID- 6241366 TI - Antibiotic resistance of Neisseria gonorrhoea in Curacao. AB - Beta lactamase producing Neisseria gonorrhoea strains are only occasionally found in Curacao; of the non beta lactamase producing strains isolated from civilians a high percentage was moderately to highly resistant to penicillin and moderately resistant to tetracyclin. These percentages were even high in the case of gonococcal strains isolated from prostitutes. Strains which are resistant to spectinomycin were not found. These findings may warrant considering the use of alternative antibiotics in the treatment of gonococcal infections in this community. PMID- 6241367 TI - [Development and regulation of ketogenesis in isolated hepatocytes in the newborn rabbit]. PMID- 6241368 TI - [Laparoscopic operations on the stomach]. AB - On the basis of an analysis of 297 laparoscopic interventions on the stomach fulfilled in 266 patients (laparoscopic puncture gastrostomy, laparoscopic ablation of polyps and foreign bodies of the stomach) it was shown that they can be used as sparing methods of the surgical treatment of some diseases of the esophagus, stomach, pancreas. PMID- 6241369 TI - [Organization of roentgenoradiological services in the RSFSR and the role of the Moscow Research Roentgenoradiologic Institute in their improvement]. PMID- 6241370 TI - [Scientific research in military medicine as a factor in improving therapeutic and diagnostic services in sanatoria]. PMID- 6241371 TI - [History of the Smolensk military hospital]. PMID- 6241372 TI - [Total activity and distribution of multiple forms of lysosomal glycosidases in subfractions of human leukocytes]. AB - Activities of N-acetyl-beta-D-hexosaminidase, beta-D-galactosidase, alpha-D mannosidase and alpha-L-fucosidase were studied in granulocytes and agranulocytes of human blood. Hexosaminidase exhibited the highest activity in the both leukocyte fractions. At the same time, activities of hexosaminidase and galactosidase were higher in a granulocytes. Activity of mannosidase was higher in granulocytes. Activity of fucosidase was similar in the both subfractions. The following results were obtained after isoelectric focusing of hexosaminidase and fucosidase isoenzymes in polyacrylamide gel. Only one form, hexosaminidase A, was found in granulocytes, whereas two enzyme forms--hexosaminidase A (main component) and hexosaminidase B (minor fraction) were noted in agranulocytes. From 4 to 5 isoenzymes of fucosidase, detected in various human and animal tissues, were observed in the both leukocyte subfractions. Specific properties of the lysosomal hydrolases activity and of their isozyme spectra in the leukocyte subfractions are discussed. PMID- 6241373 TI - [Biochemical diagnosis of sialidosis in a child with a "cherry spot" in the fundus oculi as the main clinical symptom of the disease]. AB - Biochemical study of a 6 years old child with decreased visus and cherry red spot but without any somatic and mental abnormalities was carried out. Leukocyte lysosomal hydrolases exhibited a distinct deficiency of neuraminidase activity in the child and a decrease of the enzyme activity in the parents of the child. The neuraminidase activity in leukocytes of mother and father constituted 37% and 53% of the control values, respectively; these data enabled to consider the parents as heterozygotes. Excretion of total sialylolygosaccharides with urine was increased 4-5-fold in the patient as compared with suitable controls. It was concluded that the patient studied was affected by sialidosis of the type I. PMID- 6241374 TI - [Effect of vasopressin on energy metabolism of the brain in adult and aged rats]. AB - Content of adenosine phosphate, creatine phosphate, Pi, lactate and ATPase activity were studied in brain of 8-10- and 25-27-months old rats. Content of ATP and ADP and the Na+, K+-ATPase activity were decreased while the level of Pi was increased in rat brain cortex during ageing. Administration of vasopressin caused an increase in lactate, Pi and Na+, K+-ATPase activity, whereas creatine phosphate decreased in the adult rat hypothalamus. Changes in energy metabolism were more pronounced in old rats: simultaneously with the decrease in creatine phosphate and more marked, as compared with adults, increase in Pi and lactate, the content of ATP decreased, ADP and AMP - increased and the Na+, K+-ATPase was distinctly activated in stem and brain cortex. PMID- 6241375 TI - [Interrelations of lysosomal enzymes of leukocytes in patients with cicatricial stenosis of the larynx]. AB - Activities of acid and alkaline phosphatases, cathepsin B, leucine aminopeptidase, N-acetyl-beta-D-hexosaminidases, beta-D-galactosidase and beta-D glucuronidase were studied in leukocytes of two groups of patients with normal and pathological healing of wounds after surgical treatment of scar stenosis of larynx. Analysis of the enzymatic activity, calculated by means of Student's test using the data of a single estimation of the activity in leukocytes before surgical treatment, did not exhibit any distinct differences in these two groups of patients. The study of interrelationship between the activities of individual enzymes by means of principles of regression analysis enabled to show that the enzymes studied were in the positive regressive relation. Pattern of enzymatic activity in leukocytes of patients with pathological wound healing was distinctly different from that of patients with normal healing in the shape of regression and, especially, in relaxation of the interrelations between phosphatases and other enzymes. The principle of regression enabled to evaluate the prognosis of postoperative development of wound healing using the preliminary estimation of enzymatic activity in leukocytes of patients with scar stenosis of larynx. PMID- 6241376 TI - [Ca2+-dependent phosphorylation and ATPase activity of cardiac muscle myosin in experimental myocardial infarction]. AB - An ATPase activity of myosin was decreased in the ischemic zone of myocardium within 24 hrs after experimental infarction in dogs. The intensity of Ca2+ dependent phosphorylation of the myosin preparation was also decreased and the rate of phosphorylation in the light chain (with molecular mass 18,000) was increased. These alterations found in the ATPase properties and phosphorylation of myosin are important for studies of pathogenetic alterations in myofibril contractile function in acute ischemia of myocardium. PMID- 6241377 TI - [Intestinal function in pipe rolling workers suffering from the lumbosacral pain syndrome]. PMID- 6241378 TI - [Electrocardiographic indices in diagnosing focal myocardial dystrophy]. PMID- 6241379 TI - [A 72-year-old female patient with severe cardiac decompensation and paraproteinemia]. PMID- 6241380 TI - [Possibilities of systemic fibrinolysis in acute myocardial infarct]. AB - Recanalisation of the infarct-related coronary artery could be achieved in 60 to 80% of patients with acute myocardial infarction by means of systemic fibrinolysis, if the interval between the onset of symptoms and the admission to therapy was less than 3 (maximal 6) hours. Fibrinolytic therapy should be combined with an exact conventional treatment in form of sedation, analgesia, oxygen delivery and optimisation of hemodynamics and metabolism with nitroglycerin, calcium antagonists and beta-blockers. Coronary angiography should be performed as soon as possible to decide about further therapy like percutaneous transluminal coronary angioplasty, coronary bypass surgery or medical treatment. PMID- 6241381 TI - [General aspects of the significance of percutaneous transluminal angioplasty for the therapy of renovascular hypertension]. PMID- 6241382 TI - [Modification of acute toxicity of selected pesticides by humic acids]. PMID- 6241383 TI - [Coronary heart disease. Surgical development in the last 10 years--status of possibilities in West Germany]. AB - This article addresses both the operative facilities for coronary bypass surgery in the Federal Republic of Germany and the surgical progress made in this field during the past 10 years. Like in many other countries, there is a continuing critical discrepancy between the number of patients offered for treatment and those operated upon. The reasons for this lack of facilities is explained. Recent moves by the respective Ministries and the public insurance system, however, have raised the expectation that this problem will be eliminated by the end of the decade. Progress in coronary surgery which is well mirrored by our own experience has undergone substantial changes in regards to patients selection and surgical approaches used. There has been a sharp increase in emergency coronary surgery. The proportion of combined procedures on the coronary arteries and myocardium or peripheral vessels has risen to approximately 10 while the rate of reoperation has not yet exceeded 5%. Resection of left ventricular aneurysms has largely been limited to patients with additional coronary stenoses and/or ventricular tachycardia. Complete revascularization (3.2 peripheral coronary anastomoses per patient) has become the rule and circular sequential vein bypass the preferred method for achieving this aim. On the basis of our experience it may be prognosticated that mammary artery bypass and open endarterectomy also of the left coronary system will play an increasing role in the near future. PMID- 6241384 TI - Seven years of coronary angioplasty. AB - The use and development of coronary angioplasty since 1977 is discussed. Initially applied to uncomplicated cases, coronary angioplasty is now successfully used in patients with multiple stenoses and distal vessel locations. Success rates have improved with increasing experience and developments in catheter technology; while this technique will probably still mainly be applied to patients with a new onset of angina pectoris and localized disease, further developments should extend its application. PMID- 6241385 TI - [Frequency of recurrence following successful balloon dilatation of coronary artery stenoses]. AB - In 333 (94%) out of 356 patients, who underwent successful TCA between October 1977 and June 1983, follow-up angiograms were performed. A total of 439 follow-up angiograms taken at 1-48 (on average 5.6) months after successful angioplasty were analysed. Restenosis rate was 12% if defined as remaining luminal widening of less than 20% compared to the situation before angioplasty. Its rate was 16% if defined as loss by at least 50% of the initial increase in luminal diameter. Restenosis rate was 17% if according to the international registry of the NHLBI defined as either loss by at least 50% of the initial increase in luminal diameter or as an increase in post-TCA-stenosis by at least 30%. When excluding those patients with restenosis who underwent repeat TCA and those with dilatation of an aortocoronary bypass stenosis the restenosis rate was reduced to 15.4%. In these two subgroups restenosis rate was 33% and 45%, respectively. Several factors may be responsible for the observed relatively low restenosis rate: Selection of patients Technique of TCA Medical treatment during and after TCA Reduction of risk factors, compliance of patients Unknown factors. Chronical medical treatment with high doses of acetylsalicylic acid, nitrates, and calcium blockers are considered most likely to be responsible for this result. PMID- 6241386 TI - [Transluminal angioplasty--unstable angina, fresh infarct]. AB - Transluminal coronary angioplasty is successfully used in stable and unstable angina. Out of 107 patients admitted with unstable angina 28% were treated medically, 24% operatively and 48% by angioplasty. In a total of 116 patients the stenosis diameter was enlarged from 75.0 +/- 11.0% obstruction to 25.1 +/- 16.4% (improvement 49.9 +/- 16.5%) without differences between concentric and eccentric or right and left coronary stenosis. In 11 out of 22 patients with total coronary occlusion of recent origin the vessel was reopened by the balloon and enlarged to a resting stenosis of 22.3 +/- 16.4%. There were no differences in the success- and the complication rate between stable and unstable angina. After successful thrombolysis residual stenoses greater than 50% are dilated during the same session. In a randomized prospective study 51 patients were dilated immediately (group I) and 48 patients (group II) treated conservatively. In group I the reinfarction- and the cardiac death-rate was two patients compared to seven patients in group II. After four weeks there was one reocclusion (3%) compared to five (17%) and a residual stenosis of 31.9 +/- 24.4% versus 78.0 +/- 15.2%. Angioplasty can be used with good results and a low complication rate in unstable angina and following successful thrombolysis. PMID- 6241387 TI - [Short intravenous infusion of streptokinase in acute myocardial infarct]. AB - A brief review is given about the results obtained with high-dose brief-duration intravenous streptokinase infusion in patients with evolving myocardial infarction. Feasibility and efficacy of the intracoronary and systemic approaches are compared. Coronary clot lysis occurs as frequently with the intravenous approach as with intracoronary application if treatment is initiated early. A longer clot lysis time often will be more than compensated by the earlier initiation of the intravenous therapy. Therefore, intravenous thrombolysis might be more effective in the salvage of at-risk myocardium. After intravenous thrombolysis coronary angiography should be performed on an elective basis 1-3 weeks after the acute infarction. At this time, about 60% of the patients have had a diameter stenosis of the infarct-related coronary artery of less than 65%. It appears that in these patients late reocclusion or reinfarction is a rare event, while it is frequent in patients with a more severe residual stenosis. Coronary angioplasty may be advisable in these latter patients. PMID- 6241388 TI - Fine structure of muscle spindles in the woodpecker (Dendrocopus major) and Quail (Coturnix coturnix japonica). PMID- 6241389 TI - [A topo-optical polarization method of activation of lymphocyte chromatin in the diagnosis of drug allergy]. PMID- 6241390 TI - [Effectiveness of the complex treatment of rubromycosis with griseofulvin, placental suspension and pentoxyl]. PMID- 6241392 TI - [Treatment of rosacea at a department of medical cosmetology]. PMID- 6241391 TI - [Humoral and cellular immunity in patients with drug-induced disease]. PMID- 6241393 TI - [Use of microtests for the early detection of syphilis]. PMID- 6241394 TI - [50th anniversary of the Turkmenistan Scientific Research Institute of Skin Diseases]. PMID- 6241395 TI - The wellbeing of the elderly. Approaches to multidimensional assessment. PMID- 6241396 TI - [Accident and compensation neuroses. Abnormal mental reactions and developments after accidents]. PMID- 6241397 TI - [Fc IgG carrying T lymphocytes in healthy adults and patients following kidney transplantation]. AB - In 28 healthy adults aged 19 to 52 years, normal values of the TG lymphocytes amount to 17.8 +/- 2.3% and 253.1 +/- 96.1 per microliters respectively and the non TG/TG ratio to 4.72 +/- 0.82. When compared with normal controls, patients on dialysis had a disturbed non TG/TG ratio (4.72 +/- 0.82 vs. 6.00 +/- 1.94, p less than 0.05). During the first posttransplant month the total TG cell count was significantly reduced, but the relative TG cell count did not significantly differ from the normal as well as praeoperative TG cell count. In connection with rejection crises we could not observe any changes in the TG subset. Beside this general dynamics we observed two different kinds of changes of the non TG/TG ratio in the individual posttransplant course. Either the non TG/TG ratio were lower than praetransplant or higher. In 9 out of 9 cases the lowering of the non TG/TG ratio (that means a relative or absolute increase of Fc-IgG receptor bearing T cells) were connected with a good graft function. In 4 out of 6 cases a postoperative increase of the non TG/TG ratio were connected with an early graft failure. A change of T subsets for the benefit of TG cells which includes suppressor cells seems to be favourable with regard to the graft survival. Therefore, we think the determination of the prae- and posttransplant non TG/TG ratio is of some prognostic value. PMID- 6241398 TI - [Professor Kuwatas' theory of the triangular structure of the marginal edge of metal-ceramic crowns]. PMID- 6241399 TI - [Psychogenically-induced lumbar pain]. AB - Diseases of the column and some psychic disturbances (e.g. neuroses) form the causes of transitory or chronic invalidity. From a psychological point of view, the lumbar region plays an important role in the polarisation of certain psychological conflicts: sexuality, aggressiveness, depression, frustration, exaggerated submission, etc. In consideration of this sensitivity of the lumbar region to certain psychic disturbances we have subjected a great number of women and men to a special neurological and clinical examination. Only in one per cent of the patients operated on no organic change was found, which underlines the importance and necessity of an appraisal of the personality of the patients with chronic, psychically caused pain. When this appraisal of the personality is omitted, diagnostic errors may occur that cannot be made good again. PMID- 6241400 TI - [Action of dicaine on the efficiency of plasmid transformation and transfection in Escherichia coli K12]. AB - The action of tetracaine hydrochloride, a local anesthetic, on the effectiveness of plasmid transformation and transfection in variants of E. coli K-12 has been studied. The concentrations of tetracaine hydrochloride used in the experiment (0.002 M) affect the level of the synthesis of most proteins in the outer membrane of these bacteria. This seems to be one of the causes of changes in the effectiveness of plasmid transformation and transfection in E. coli K-12. PMID- 6241401 TI - [Data on the inoculation coverage against diphtheria, pertussis and tetanus of children in the 1st 3 years of life]. AB - Selective analysis revealed the insufficient coverage of children aged up to 3 years with immunization against diphtheria, pertussis and tetanus in Baku, as well as lagging behind the established vaccination schedule. The absence of the prophylactic immunization of children during first 3 years of their life was mainly due to such medical contraindications as acute respiratory diseases, neurological diseases and various dermal manifestations. At the same time no sparing methods of immunization were used. PMID- 6241402 TI - [Epidemiological characteristics and the importance of carriers of the surface antigen of the hepatitis B virus (HBsAg)]. AB - The occurrence of HBsAg carriership in Leningrad has been found to be 1.4% according to the results of countercurrent immunoelectroosmophoresis (CIEO) and 2.1% according to the results of the passive hemagglutination (PHA) test. In children HBsAg occurs with higher frequency: 1.9% according to the results of CIEO and 3.4% according to the results of the PHA test. The latter test reveals HBsAg carriers more completely, especially in women who have usually less pronounced antigenemia than men. Most of chronic HBsAg carriers are patients with chronic forms of hepatitis B (chronic active hepatitis and chronic persistent hepatitis); frequently they become the source of infection among their relatives under the conditions of family contacts. A complex of antiepidemic measures is necessary in the foci of chronic HBsAg carriership. PMID- 6241403 TI - [Tularemia on the Kola Peninsula]. AB - In 1982 Francisella tularensis was isolated for the first time on the Kola Peninsula from rodents caught in the environs of Kirovsk and Nickel. This fact confirmed the suggestion concerning the existence of the natural foci of tularemia on the Kola Peninsula. PMID- 6241404 TI - [Staphylococcal induction of suppressors of macrophage phagocytic activity]. AB - During experimental infection caused by S. aureus, strain Smith, the formation of suppressors of the phagocytic activity of macrophages was induced in the peritoneal cavity and the spleen of intact and infected mice. Thus, in the cultivation of macrophages of the infected mice together with nonadhering cells of the peritoneal exudate of the infected animals the phagocytic index was 0.75 +/- 0.09; in the presence of splenocytes of the infected mice the phagocytic index for macrophages of the intact and infected animals was 0.64 +/- 0.12 and 0.89 +/- 0.04, respectively. Splenocytes of the intact mice, when cultivated together with macrophages of the infected mice, enhanced phagocytic activity during the first hours of cultivation and suppressed it after prolonged cultivation (12 hours); the phagocytic index was 1.37 +/- 0.18 and 0.82 +/- 0.03, respectively. PMID- 6241405 TI - [Ultrastructural aspects of testicular interstitial cells in the bat (Vesperugo savi)]. AB - The fine structure of the testicular interstitial cells (Leydig cells) was studied in the bat (Vesperugo savi) during the seasons in connection with his peculiar spermatogenesis activity and biologic cycle. Such cells have ultrastructural aspects similar to those delineated for the other species. Only the smooth endoplasmatic reticulum, mitochondria and lipid droplets changes their morphologic features during the year. In fact in the summer-autumn season there is an intense spermatogenesis. The Leydig cells show more developed smooth endoplasmatic reticulum and lipid droplets of different size of peripheral electron-density. During the winter-spring season there is not spermatogenesis. The testicular interstitial cells have a poor smooth endoplasmatic reticulum and numerous bodies like lipofuscin pigments. When the bat wakes from his lethargic sleep, the ultrastructural aspects of Leydig cells are the prove of a smaller synthesis activity. These results confirm the dependence of testicular interstitial cells from the spermatogenic cycle. PMID- 6241406 TI - [The fine structure of spermatozoa from Chiroptera]. AB - The fine structure of hibernating bat spermatozoa (Vesperugo savi and Rinolophus f.e.) has been studied by SEM and TEM, during their prolonged storage in female reproductive tract. The main morphological aspects of sperm portions: head, neck, middle piece, principal piece and terminal piece have been described. The Author besides comparisons with other mammalian species and Chiroptera, suggests some typical ultrastructural features of these Chiroptera, as the complete absence of vacuoles in the nuclear chromatin and corrugated structures in the post-acrosomal zone. Moreover electron-dense material in the subacrosomal space and three mitochondria in the neck were observed. Two areas of fusion between outer dense fibers 3 and 8 and the inner ends of the respective longitudinal columns of the fibrous sheath and asymmetrical arrangement of the outer dense fibers of the principal piece were found. PMID- 6241407 TI - [Weight increase and chronic experimental poisoning by tobacco smoke in the albino rat. Effect of protection with mineral waters]. AB - The Authors refer to the results of an experiment conducted on albino rats chronically intoxicated with tobacco smoke. Several groups of animals were contemporaneously protected, by drinking or by inhaling or by both methods, by a beneficial sulphureous water with a varying sulphydrometric degree, and in one experiment, by inhaling a hypertonic salso-bromo-iodic water. In all cases, it was possible to observe that in the adopted experimental conditions, the chronic intoxication from tobacco smoke slowed the weight increase of albino rats subjected to intoxication and not protected, both as regards non-intoxicated animals and as regards intoxicated animals protected by one of the studied waters. There were no statistically significant differences between the weight increase of the animals protected by the drinking or inhaling methods while protection via both methods resulted statistically more efficacious than protection by one single method. PMID- 6241408 TI - [Retrospective study of 50 cases of spinal meningioma]. AB - The clinical history prior to surgery of 50 consecutive cases of spinal meningioma was reviewed. The following features turned out to be particularly interesting: a 7:1 female to male ratio; the symptoms began after the sixth decade in no less than 66% of patients; only 36% were correctly diagnosed as having spinal tumor at the first clinical examination; the average duration of symptoms was 16 months prior to surgery. Such findings are discussed and compared with those of the previous reports. PMID- 6241409 TI - [Malignant centro-facial granuloma. Clinical contribution]. AB - The mid-face malignant granuloma represents an exceptionally rare disease. Its etiology is unknown and the prognosis is dismal. Characteristics pathological features are represented by granulomatous, ulcerative and lesions, with a destroying tendency. The AA., in reporting a recently observed case of the disease, stress the difficulties encountered in the diagnosis and analyze its clinical course typically showing relapsing episodes. Therapeutic strategies adopted in the various phases of the disease are discussed. PMID- 6241410 TI - [Sacral herpes zoster: a cause of urination and defecation disorders]. AB - A case of sacral herpes zoster associated with alteration of urination and defecation is presented. The pathogenetic mechanisms of these unusual complications are discussed. PMID- 6241411 TI - [Ultrasound in the study of the functional dynamics of the female genitalia]. AB - The Authors have carried out this survey aiming at having at their disposal biometric indexes to be used in the dynamic and functional study of the female genitalia, since the purely anatomic data cannot be correlated white absolute certainty to the ultrasound data. The survey has been carried out on 42 women of an age between early childhood and late menopause. The patients in their fertile age were examined every other day, from the 10th day of the menstrual cycle; women in menopause or in their pre-puberal age were examined only once, to a total of 158 scans. In each woman the linear and volumetric measurement of the uterus, ovary, ovarian follicle and of the tube has been studied. The results were in conformity with those already reported in the literature. PMID- 6241412 TI - [The ambulatory ECG in the evaluation of coronary insufficiency]. AB - To assess the diagnostic value of continuous ambulatory ECG in exercise angina pectoris, 49 males (mean age 52, 1 years), with exercise ischemic ECG changes and positive coronary angiography were evaluated. Ischemic ST-changes were detected by ambulatory ECG in 47% of those patients; most of these ST segment displacements were asymptomatic and a lot of them occurred at rest. In order to assess the specificity of ambulatory ECG, 90 healthy subjects (47 males and 43 females, mean age 43,6 years), were also evaluated 8.9% of these subjects developed ischemia like episodes of ST segment deviation. We conclude that in exercise angina pectoris the ambulatory ECG allows to recording silent ST segment changes, in spite of a poor diagnostic sensitivity. The low specificity of ST segment depression recorded by ambulatory ECG must be also emphasized. PMID- 6241413 TI - [Volumetric growth of the gestational sac: reliability and clinical limits]. AB - Thanks to the continuous progress of the ultrasound scanning in obstetrics it is now possible to see the gestation sac already the 5th week of the pregnancy. Aiming to simplify the methods, of the past, the authors suggest the utilisation of a very simple but at the same time extremely accurate methodology to measure the volume of the gestational sac. The comparison between the data which have been obtained with this study and those reported in the literature showed a substantial uniformity, though the results came from different procedure. At the end of the study, the uses of this parameter as well as its application in the solution of that particular problem in the ultrasound diagnosis which is the "blighted ovum" are explained. PMID- 6241415 TI - [Laryngeal plasmacytoma. Observations on a clinical case]. AB - Extramedullary solitary plasmocytoma (E.S.P.) is an undoubtedly rare neoplasm for the head and neck areas and even more for the larynx. The Authors take a case observed by them as a starting point for remarking its symptomatology and unforeseable development as well as various and unsteady histopathology. Afterwards they dwell upon the differential diagnosis with the multiple myeloma and the plasmacell granuloma. Such diagnosis is mainly suggested by the histopathological investigation with the support of clinical, blood and radiologic tests. The preferential treatment and the need of a long-term and careful follow-up are the suggested. PMID- 6241414 TI - [Limitations in opening the mouth after temporal craniotomy. Observations on 3 clinical cases]. AB - The authors describe 3 cases of mouth-opening limitations and dyskinesia of the remaining mandibular movements, of different degrees of severity, arisen following a cicatricial retraction of the temporal muscle, caused by neurosurgical accesses to the underlying encephalic regions. Having kept in mind the afflictions that could cause an analogous symptomatology, the authors stop to consider which is the most suitable kind of treatment (surgical or rehabilitative) in these specific cases. For both kinds of treatment, corresponding to the specific indications, they propose techniques confirmed by their personal experiences. PMID- 6241416 TI - [Neurofibroma of the tongue: a clinical case]. AB - The Authors report a case of neurofibroma of the tongue, observed by them. Its peculiarities and the differential diagnosis with neurinoma and other affections are discussed, mostly pointing out its rarity, epidemiological data and histogenesis. After a review of the literature concerning these forms, the Authors dwell upon the histopathologic characters of neurofibroma, the peculiarities of the case reported by them, considering the real rareness of an isolated report of neurofibroma, typical element of Recklinghausen's disease. PMID- 6241417 TI - [A case of lipoma in a pharyngeal site]. AB - The Authors describe a clinical case of lipoma examined by them in a retropharyngeal site. Reports published in literature show the extreme rarity of a pharyngeal localization of lipomas. The symptomatology and numerous differential diagnoses are examined. Of the instrumental diagnostic examinations, the stratigraphy of the pharynx and CAT were decisive in identifying the benign nature of the neoformation. In the clinical case described, needle biopsy did not produce any decisive diagnostic elements. In agreement with other Authors, the therapy of choice to be followed is a surgical procedure. PMID- 6241418 TI - [Stress in internal medicine. Introduction to the subject]. PMID- 6241419 TI - Twin studies of disease heritability based on medical records: application to acne vulgaris. AB - Establishment of the Kaiser-Permanente Twin Registry permitted the study of disease heritability in twins based on review of the twins' medical records. The records of 930 pairs of twins were reviewed. Based on previous questionnaires, 342 pairs were MZ, 345 were DZ and 243 were of unknown zygosity. Because of the age distribution of these twins and the time period in which they received care, conditions of youth, such as acne vulgaris were most reliably studied. Heritability of acne was assessed in three ways; all indicated a substantial genetic influence. Certain problems with twin studies using medical records became apparent: 1) Zygosity information is often lacking; 2) Differing times and durations of observation of the two twins in each pair must be accounted for; 3) Categorization by diagnosis is difficult and strict criteria for diagnosis may be impractical; 4) Patients' behavior that affects assessment of disease concordance must be considered; 5) The order in which records are reviewed may influence apparent concordance. PMID- 6241420 TI - Cytogenetic findings in moderate and severe mental retardation. A study of an institutionalized population of 1991 patients. AB - The cytogenetic data of a large scale study in an institutionalized population of 1991 moderately and severely mentally retarded patients are presented. In 21.3% of these patients a chromosomal aberration was diagnosed (14.9% Down syndrome patients and 3.5% "other chromosomal anomalies"). A fragile X screening was performed in 354 males, and was found to be positive in 57 (16.1% positive). Different chromosomal variants were present in another 6% of this population. Detailed results are presented on the different groups of chromosomal aberrations. PMID- 6241421 TI - [Pathogenesis of cardiac hypertrophy: the role of noradrenaline]. PMID- 6241422 TI - Nonsurgical reperfusion in evolving myocardial infarction. PMID- 6241423 TI - Prions: novel infectious pathogens. PMID- 6241424 TI - [Inhibitory effects of aromatic retinoic acid analog, administered alone or in combination with mitomycin C, on the in vitro growth of rat bladder carcinoma cells]. AB - The effects of an aromatic retinoic acid analog (Ro 10-9359), its metabolite (Ro 10-1670) and mitomycin C (MMC) on the in vitro growth of rat bladder carcinoma cells, BC50-TC were examined. The growth of the cells treated with 10(-4) M of either of the retinoids for 1 hour was not inhibited. The growth of the cells was inhibited by 37% and 93%, respectively, by the 3-day treatment with Ro 10-9359 and Ro 10-1670, at the concentration of 5 X 10(-5) M. The retinoids given in combination with MMC produced additive effects. Slight synergism was suggested at high concentrations of the retinoid. The fact that the retinoids exhibited anti tumor activity in vitro might preclude indirect effects from being the only factor in the inhibition of the tumor growth in vivo, but the fact that antagonism with MMC did not occur in vitro whereas it did in vivo suggests that the indirect effects of the retinoid might be more important in mediating the anti-tumor effects. Regardless of the mechanism of action, care should be taken when prescribing retinoids with MMC or other cytotoxic agents. PMID- 6241425 TI - [Induction of immunologic tolerance to transplantation antigens using conditioning of the lymphocyte genome of the recipient with ribonucleic acid from the donor]. AB - The phenomenon of specific immunosuppression which we call "immunologic tolerance" constitutes the final result common to diverse processes partially known. The study of the phenomena inter or intra cellular involved in the divese mechanisms of production, however constitutes a field which is quite obscure. The explanation of these phenomena could offer us some fundamental knowledge towards the better understanding and subsequent manipulation of the process. This present project of investigation proposes to study the possibility of transferring one of these states of tolerance which is better established as is the spontaneous tolerance to the proper antigens of an animal (donor) to a second animal (receptor) genetic and for that reason, antigenically different, through an informational molecule such as the ribonucleo acid (RNA) extracted from the donor animal. This hypothesis is based theoretically on the following points: 1) The state of "self-immunologic tolerance" is probably an active and dynamic phenomenon, in which one can determine the presence of lymphocytes with receptors for proper antigens, without establishing in normal conditions an efferent phase of the immunologic answer, which determines an effect on this antigen. 2) The effective immunologic reactivity (allergic answer) of a determined animal is transferable to a second non-sensitized animal through RNA from the first animal. In this study we present the results of the conditioning of the allogenic reactivity of one strain of mice, through the exposition of the same to RNA extracted from one congenic-resistent strain with respect to first.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 6241426 TI - Current concepts on the relationship between immunodeficiency and allergy. AB - The relationship between immunodeficiency and atopy represent one of the most significant yet at the same time one of the least understood phenomena in medicine today. This paper will therefore attempt to review the present state of knowledge. Current data focusing on the role of histamine as a negative feed-back regulator of the immune system will also be summarized. It has recently become evident that although several lines of evidence have documented abnormal suppressor T cell functions or numbers in the atopic state, the exact mechanism, however, is not clear yet. It would be important to assess whether the disturbed T cell activity is primary or secondary to the other findings in the atopic diathesis. PMID- 6241427 TI - The fetus as an allograft: evidence for antiidiotypic antibodies induced by pregnancy. AB - We tested sera from 20 women [9 parous, 8 with no children, and 3 with abortion(s)] for inhibition in mixed lymphocyte culture (MLC). In these experiments, the responder (wife) lymphocytes were treated with autologous serum and rabbit complement and then tested for responses against stimulator cells from the husband and from third-party allogeneic donors. The results demonstrate that antibodies capable of inhibiting responses of wife's lymphocytes to husband's cells in MLC are present in sera from parous women, but not in women without children and in women with abortion(s). The MLC-inhibiting activity in parous women sera was in the IgG fraction. The results from immunofluorescence and absorption experiments suggest that the inhibition in MLC was due to antibodies directed against recognition sites on wife's T lymphocytes against husband's alloantigens. These observations suggest that antiidiotypic antibodies against husband-specific idiotypes on wife's lymphocytes could be induced by pregnancy and that maternal tolerance to fetus may be attributable to a similar mechanism occurring in vivo. PMID- 6241428 TI - Rat pregnancy induces two suppressor cell activities. AB - Pregnancy in rat is able to stimulate two suppressor cell activities. One is specific to the paternal histocompatibility antigens and it resides in the T lymphocyte population. The second is nonspecific and is of non-T nature. The use of various methods for pseudopregnancy and deciduoma installation has allowed the demonstration of two inducing circuits: (a) the presence of fertilized ova in the female genital tract and (b) the progestation hormonal status. PMID- 6241429 TI - Rat pregnancy immunoregulatory circuits are progestation hormonal status, decidual tissue, embryo-trophoblast and late pregnancy changes dependent. AB - We have tested the spleen cells of rats for their reactivity to mating and unrelated (third party) strain alloantigens during pregnancy, pseudopregnancy, and traumatic deciduoma installation. By cytotoxic T-lymphocyte assays, after 7 day one-way mixed lymphocyte cultures (MLC), we detected the presence of many immunoregulatory circuits among rat pregnancy and postpartum. They are progestation hormonal status, decidual tissue, embryo-trophoblast, late-pregnancy parturition-associated changes, and lactation-hormonal-status dependent. PMID- 6241430 TI - Seminal plasma abrogates the postcoital T cell response to spermatozoal histocompatibility antigens. AB - The T-cell responses to spermatozoal histocompatibility antigens were studied in the uterine regional lymph nodes of female rats by a specific cytoadhesion assay. The antigenic challenge was introduced either by artificial insemination with syngeneic or allogeneic epididymal spermatozoa or coitus. The uterine regional T cell response to allogeneic spermatozoa following artificial insemination was measureable after 2 days and continued undiminished until day 5. In contrast, the measurable response to allogeneic coital challenge peaked on day 3 and disappeared by days 4-5. Since the difference between the two stimuli involved the presence of seminal plasma, these results indicate a possible immunoregulatory (suppressive) effect of seminal plasma on the cellular immune reaction of the female to the male alloantigens after mating. PMID- 6241431 TI - Immune-mediated migration of neutrophils into the uterine lumen of guinea pigs. AB - Metritis was elicited by intrauterine infusion of tuberculin or killed Campylobacter fetus ssp. venerealis into vaccinated guinea pigs and lipopolysaccharide or immune complexes into normal animals. The local inflammatory response to intrauterine infusion of antigens, lipopolysaccharide, and immune complexes was determined by changes in differential cell counts in the uterine lavage fluid and by histopathological examination of uterine tissue. The percentage of neutrophils was significantly (p less than 0.01) greater in uterine lavage fluid collected at 4 hr after infusion of tuberculin into animals vaccinated locally (intrauterine) with M. tuberculosis than in animals vaccinated parenterally (subcutaneously). In contrast, the local response to infusion with C. fetus ssp. venerealis was approximately the same in animals vaccinated intrauterine and subcutaneously with Campylobacter. The systemic response, measured by the delayed type hypersensitivity cutaneous reaction to intradermal injection of tuberculin, was significantly (p less than 0.01) greater in animals vaccinated subcutaneously than intrauterine. Similarly, the concentration of Campylobacter antibody in the serum of animals vaccinated subcutaneously was significantly (p less than 0.01) greater than in guinea pigs vaccinated intrauterine. The intrauterine infusion of immune complexes, composed of C. fetus ssp. venerealis and corresponding antibody, into the uterus of normal guinea pigs stimulated neutrophil migration into the uterine lumen. Infusion of lipopolysaccharide also stimulated neutrophil migration into the uterine lumen. A correlation between an increased percentage of neutrophils in uterine lavage fluid and infiltration of the uterine epithelium with neutrophils was observed. PMID- 6241432 TI - A combined assay of three lysosomal marker enzymes: acid phosphatase, beta-D glucuronidase, and beta-N-acetyl-D-hexosaminidase. AB - A simplified and rapid method for simultaneous activity measurements of three lysosomal marker enzymes, acid phosphatase, beta-glucuronidase, and beta-N-acetyl D-hexosaminidase is described. The incubation is carried out in a single test tube and stopped by adding an alkaline sodium dodecyl sulfate solution, thus avoiding centrifugations and allowing for higher Triton X-100 concentrations in the incubation media. Two products of the beta-glycosidases (phenolphthalein and 2-nitrophenolate) are measured spectrophotometrically at the respective wavelengths (555 and 420 nm), and one of the acid phosphatase products is quantitatively determined by measuring inorganic phosphate. PMID- 6241433 TI - A method for the determination of total, free, and 5-fluorodeoxyuridylate-bound thymidylate synthase in cell extracts. AB - A radiochemical assay for thymidylate synthase (EC 2.1.1.45, dTMP synthase), which permits the accurate determination of total, free, and 5-fluoro-2' deoxyuridylate (FdUMP)-bound enzyme in cells exposed to the 5-fluoropyrimidine anticancer agents, is described. The total intracellular concentrations of dTMP synthase (free plus FdUMP-bound enzyme) in extracts from CCRF-CEM leukemic cells incubated with 5-fluoro-2'-deoxyuridine were determined following dissociation of the covalent dTMP synthase-5,10-methylenetetrahydrofolate-FdUMP ternary complex in the presence of the substrate, 2'-deoxyuridine-5'-monophosphate. The addition of substrate prevented reformation of the ternary complex during the dissociation procedure, and allowed complete recovery of FdUMP binding sites in cells exposed to a high concentration of 5-fluoro-2'-deoxyuridine. After removal of the substrate by charcoal adsorption, the concentration of total FdUMP binding sites was determined by titration of the enzyme with a saturating concentration of [6 3H]FdUMP and 5,10-methylenetetrahydrofolate. The concentration of FdUMP-bound dTMP synthase was then calculated as the difference between the total and free (without prior ternary complex disruption) enzyme values. The high sensitivity of this assay coupled with its ability to accurately quantitate both free and FdUMP bound dTMP synthase in cells exposed to a wide range of fluoropyrimidine concentrations should make it useful for a variety of experimental and clinical studies. PMID- 6241434 TI - A rapid-filtration technique for membrane fragments or immobilized enzymes: measurements of substrate binding or ion fluxes with a few-millisecond time resolution. AB - The construction and use of a filtration system with milliseconds time resolution is described here. This apparatus allows measurements of substrate binding to immobilized enzyme or ion fluxes through membrane vesicles to be performed over a very large time scale, from 10 ms to seconds. The main advantage of this system compared to the widely used quench-flow technique is that it does not require the use of an inhibitor. Following adsorption of the enzyme in an adequately chosen filter, the reaction is allowed to proceed within the filter during a forced filtration of a buffer containing the reactive substrate (or of a washing solution in the case of efflux measurements). The design allows the duration of filtration and buffer flux to be finely and reproducibly controlled. This paper illustrates the use of this rapid-filtration system for time-resolved measurements of calcium binding and transport by sarcoplasmic reticulum Ca-ATPase and of the initial phase of ADP transport by the ADP/ATP carrier of intact mitochondria. PMID- 6241435 TI - A one-step enzymatic assay for sucrose with sucrose phosphorylase. AB - A one-step, enzymatic assay for sucrose using sucrose phosphorylase is described. Sucrose phosphorylase, which is now commercially available, was isolated from Leuconostoc mesenteroides strain B-1200 and partially purified by ammonium sulfate precipitation. Samples containing 5 to 80 nmol of sucrose are mixed with potassium phosphate, NAD, sucrose phosphorylase, and two commercial enzymes, phosphoglucomutase and NAD-accepting glucose-6-phosphate dehydrogenase. After 30 min incubation at room temperature, absorbance at 340 nm is proportional to initial sucrose content. A 20-fold molar excess of glucose or a twofold excess of fructose have no effect on the assay, while a fourfold excess of fructose interferes with the assay by decreasing absorbance ca. 20%. This assay was designed to provide a rapid method for determining sucrose in studies of sugar transport by plants. To test the assay, corn pedicel extracts were assayed enzymatically and by high-pressure liquid chromatography. Estimates of sucrose content made by the two methods were equivalent, and exogenous addition of sucrose to these samples resulted in the expected increase in apparent sucrose content. PMID- 6241436 TI - [Pseudoscleroderma and sclerodermiform states]. AB - Pseudo-scleroderma should not be confused with true scleroderma, the prognosis of which is unpredictable and often serious. Progressive acrosclerosis must be differentiated from Raynaud's disease, congenital or hereditary disorders of unknown aetiology: Werner's syndrome, acrogeria and progeria; Rothmund-Thomson's syndrome, Steinert's disease, phenylketonuria, disorders of glycogen metabolism; metabolic disorders: mutilating acropathies, scleromyxoedema, porphyria cutanea tarda; occupational and iatrogenic disorders: acroosteolysis, toxic epidermic syndrome (Spain), scleroderma-like change induced by bleomycin, chronic graft versus-host disease; and leprosy. Acute diffuse scleroderma should not be confused with Buschke's scleroedema, sclerema neonatorum, systemic amyloidosis and scleroderma-like changes in hypothyroidism. Linear pseudo-scleroderma is suggested by the following scleroderma-like conditions: facial hemiatrophy, acrodermatitis atrophicans, melorheostosis, pseudo-scleroderma after corticosteroid injection, and cutaneous lesions in carcinoid syndrome. Scleroderma in plaque must be differentiated from hypodermitis sclerotisans, panatrophy and localized lipoatrophies, hypodermitis after vitamin K injection, basal cell carcinoma, necrobiosis lipoidica, vitiligo, chronic radiodermatitis, cutaneous lymphatic invasion. Scleroderma-like changes after drug injection (vitamin B12, progestin), anetoderma barely resemble morphea guttata. PMID- 6241437 TI - [Incidence and severity of cutaneous adverse effects of drugs]. AB - The frequency of adverse cutaneous reactions to drugs is generally overestimated in important prospective studies. Nevertheless, the responsibility of some drugs considered as allergenic (Allopurinol, nonsteroidal anti-inflammatory drugs) appears to be underestimated. The type of eruption, its topography and duration are the most important criteria of severity. In the Geneva University Clinic of Dermatology, adverse cutaneous reactions to drugs occurred (mean of 6 years) in 1,2 p. 100 of all outpatients and in 4,4 p. 100 of all inpatients. The disease was severe in 9 p. 100 of patients hospitalized for adverse cutaneous reaction to drugs. PMID- 6241438 TI - [Drug eruptions caused by noncorticoid anti-inflammatory agents]. AB - Non-steroidal anti-inflammatory drugs (NSAI) may elicit various kinds of cutaneous side effects. The commonest ones are non-specific erythematous eruptions, sometimes with a phototoxic distribution, and urticaria. Vasculitis and severe bullous eruptions (Stevens-Johnson's syndrome and Toxic Epidermal Necrolysis) are rare but may have severe outcomes. The overall incidence of cutaneous reactions is about the same for all NSAI, 1 to 3 p. 100, during the clinical studies performed before marketing the drug, but this increases afterwards (up to 45 p. 100 for Benoxaprofen). Drugs with long half-lives may carry a higher risk for severe cutaneous reactions. NSAI are now the main cause of drug induced TEN. Urticarial reactions seem related to pharmacological phenomena while the pathogenic events leading to other kinds of skin reactions remain unknown. An hypersensitivity reaction is postulated. The therapeutic value of corticosteroids for the severe cutaneous side effects of drugs is still controversial. PMID- 6241439 TI - [Drug eruptions caused by lithium salts]. AB - The systemic complications of therapy with lithium are well known, but toxidermia has only been recognised since 1968. The carbonate (Teralithe) is the lithium salt which is mainly responsible, leading to minor dermatoses: oedema, pruritus, alopecia, urticaria, purpura, allergic vasculitis, pretibial ulceration. Some more specific conditions have been individualised by their severity and rarity: acne form eruptions, seborrheic dermatitis, follicular keratoses and psoriasis like dermatosis as well as true psoriasis induced or aggravated by lithium. The authors review the literature and discuss the pathogenesis of these toxidermias. The cause of some dermatoses can be explained, especially the allergic vasculitis and psoriasis lesions. The underlying mechanism of most of these conditions remains unknown, but excessive tissue concentrations of the drug probably play an important role in inducing these complications. PMID- 6241440 TI - [Skin manifestations observed during treatment with penicillamine and its derivatives]. AB - Many forms of toxidermia are observed during D-penicillamine therapy. The exact type seems to depend on the pathology for which the drug was prescribed; pemphigus during rheumatoid arthritis, perforating serpiginous elastoma in Wilson's disease, cystinuria... The two physiopathogenic mechanisms discussed, an autoimmune reaction and a direct action of D-penicillamine on the skin, would seem to be complementary. PMID- 6241441 TI - [Cutaneous paraneoplastic syndromes]. AB - The authors list the really significant paraneoplastic cutaneous syndromes: acanthosis nigricans, paraneoplastic acrokeratosis, acquired ichthyosis (and eventually the "explosive" onset of seborrheic warts) and a special type of desquamative circinate erythema (erythema gyratum repens). The possible paraneoplastic character of other conditions is also discussed: dermatomyositis, necrosing vasculitis, autoimmune bullous conditions and pruritus "sine materia". PMID- 6241442 TI - Biochemical study of pentachlorophenol workers. PMID- 6241443 TI - [Pityrosporum ovale in keratotic lesions of seborrheic areas]. AB - The Pityrosporum ovale (PO) is demonstrated in various percentages of the keratotic lesions of the seborrheic areas depending upon the techniques. The accumulation of horny material most probably enhances the multiplication of the yeast and makes its demonstration easier. The PAS technique prevails upon the mycological ones (77 p. 100 versus 50-65 p. 100). PO proliferates only in the keratin layer; there are isolated spores, small clusters or even large stratified colonies. On the other side the prevalence of PO does not differ significantly whatever the ultimate diagnosis of seborrheic keratosis, actinic keratosis, naevocellular nevus or vial wart. Its multiplication within the keratin layer of the lesions does not make any difference as far as the lymphocytic infiltration of the dermis is concerned. PMID- 6241444 TI - [Brazilian pemphigus in a child in French Guyana. Discussion on the clinical polymorphism and epidemiology of the disease]. AB - The observation in French Guyana of pemphigus foliaceus having long mimicked eczema or psoriasis and turning 5 year later as an exudative erythroderma, points out the clinical polymorphism of the disease. Several clinical features are analysed that might support the hypothesis of autonomy of the Brazilian type: such as for example joint involvement. But the main point concerns epidemiology since this disease seems to spread out from the classical endemic Brazilian provinces to northern countries as socio-economical conditions improve in the south. PMID- 6241445 TI - Calcium antagonists and cardiovascular disorders. AB - All calcium antagonists have the ability to decrease the symptoms and signs in some patients with ischemic heart disease and help lower the blood pressure in hypertensive persons, but in clinical doses nifedipine does not exhibit antiarrhythmic properties, although these are an important part of the action of verapamil, diltiazem and some substances with a similar chemical structure. In certain disorders beta-adrenergic blocking drugs are useful adjuncts, and under some circumstances, particularly variant angina and supraventricular arrhythmias, specific calcium antagonists are the drugs of choice. More data are needed to define the role of calcium antagonists during cardiopulmonary bypass, in the protection of the ischemic myocardium, in the management of hypertrophic cardiomyopathy and in specific cases of primary pulmonary hypertension. When used with an appropriate sense of perspective and careful observation, calcium antagonists provide useful additional means of helping selected patients suffering from particular cardiovascular diseases. PMID- 6241446 TI - Foetal protection against abortion: is it immunosuppression or immunostimulation? PMID- 6241447 TI - The mechanism of survival of the fetal allograft. PMID- 6241448 TI - How did your mother not reject you? PMID- 6241449 TI - Humoral keystones in the gestational voussoir. PMID- 6241450 TI - Local suppressor cells and the success or failure of the "foetal allograft". PMID- 6241451 TI - Speculations on how Ia antigens (Ir genes) influence the specificity of the immune response. AB - A model based on different molecular requirements for triggering helper T cells and B cells to proliferate and differentiate is developed. This model offers an explanation for the differing specificity of the T-cell and B-cell receptor repertoires in responding to foreign protein antigens. In addition, it addresses the central paradox in understanding the mechanism by which class II MHC molecules regulate the immune response, namely the problem of how one or a few Ia molecules influence the specificity and degree of immune response to many different complex protein antigens. PMID- 6241452 TI - On the phenomena accompanying the absence of immune rejection of the conceptus by the pregnant mother. PMID- 6241453 TI - The synaptonemal complex in genetic segregation. PMID- 6241454 TI - Glycosylation mutants of animal cells. PMID- 6241455 TI - Trisomy in man. PMID- 6241456 TI - [Histochemical study of the rat placenta after experimental administration of a psychotropic drug during pregnancy]. PMID- 6241457 TI - [Policy guidelines and practical considerations for the development of technology at the Instituto Nacional de Cardiologia de Mexico]. AB - In order to face the current economical problems of the country, our Institute has intensified its efforts to replace the imports of medical goods by developing its own medical technology. This article summarizes what we have achieved in this field and describes the rules to be followed in the future. We describe the program on the designing and development of heart valve prosthesis together with an hydraulic-electrical system to test them. In the field of computed instruments, we have developed a system of "synchronos color pictures" to be applied in nuclear medicine. In the field of electrocardiography; an EKG paste, a computed program for automatic EKG interpretation and a "filter" of the 60 cycle interference. The Institute is engaged in the designing of a sophisticated EKG machine at low cost, and EKG tracing simulator for teaching purposes. These programs have been shared with others institutions of the country. PMID- 6241458 TI - [Effects of several anti-arrhythmia agents on excitability and conduction depressed by digitalis agents]. AB - Digitalis intoxication is characterized by the appearance of most of the types of severe arrhythmias described and also by important disturbances of cardiac excitability and impulse propagation. Most of the antiarrhythmic agents that are used in the treatment of these conditions also depress excitability and impulse propagation. These characteristics are frequently responsible of severe complications. The purpose of this paper is to determine the type of interactions that exist between digitalis and some antiarrhythmic agents, and compare them with the effects of magnesium. The experiments were done in several groups, of dogs anesthetized with pentobarbital and with the chest open. Excitability, conduction time and functional refractory period were determined using the classical methods. The protocol used consisted in the comparison of the actions of toxic doses of digitalis on excitability and conduction times of the atrial and ventricular tissues, under control conditions and in the presence of therapeutic doses of procainamide, lidocaine and magnesium. The results showed that procainamide worsened the depression of excitability and conduction produced by digitalis intoxication, while lidocaine does not add to the digitalis effects and in some cases it produces a partial improvement of these parameters. Magnesium completely reverts the effects on excitability and conduction. These results provide us with rational pharmacological bases for the treatment of digitalis intoxication and suggest that magnesium could be very useful in the management of patients with severe digitalis intoxication. PMID- 6241459 TI - [Hemodynamic study in hypertensive cardiopathy under ischemia induced by atrial stimulation in the absence of fixed coronary obstructions]. AB - With the purpose to study the haemodynamic changes that occur with myocardial ischaemia induced by atrial pacing (AP) in hypertensive heart disease, we studied 7 patients with such condition, all of them with a long time history of systemic hypertension, electrocardiographic signs at rest of left ventricular hypertrophy and ST-segment depression, at least of 0.5 mm. All the patients showed normal coronary arteries in angiocardiogram. AP was started 10 beats above the basal heart rate with increments of 10 beats every 2 minutes until a ST-segment depression at least of 2 mm was obtained which occurred in all the cases studied. After every 2 minutes of AP a simultaneous 12-leads electrocardiogram recording and left ventricular and aortic pull-back pressure were obtained. At the desired end point the AP was abruptly stopped and the same parameters were registered at 3, 5, 10 and 15 minutes until recovery. During AP the left ventricular systolic pressure (LVSP) did not show any significant change, with the exception of a patient who experienced angor pectoris during the proceeding. The left ventricular end-diastolic pressure (LVEDP) increased in 3.4 +/- 1.7 mmHg, change that was statistically significant (p less than or equal to 0.01) but not hemodynamically important since only in one patient it increased above the normal levels (from 13 mmHg basal to 17 mmHg during AP). In contrast, LVEDP markedly rose above normal when AP was stopped. It is concluded that neither LVEDP nor LVSP play an important role in the genesis of the ST segment depression seen in these patients. It is showed that, similar as in patients with obstructive coronariopathy, these cases work on a depressed Starling curve during AP and its recovery for what is thought that the functional meaning of ischaemia for both entities is similar no matter that their pathogenetic mechanisms are different. PMID- 6241460 TI - [Pneumonitis caused by hypersensitivity to the antigen(s) of pigeons. I. Clinical study]. AB - We studied twenty six patients with hypersensitivity pneumonitis due to pigeon antigens (pigeon breeder's disease). This insidious illness, causes an interstitial lung disease, with restrictive pattern and also pulmonary hypertension. Most of the cases showed circulating antibodies against pigeon serum proteins, polyclonal hypergammaglobulinemia and rheumatoid factor. Treatment based on avoidance of pigeon droppings and glucocorticoids gave good results. PMID- 6241461 TI - [Mitral valve replacement in children with a Bjork-Shiley prosthesis]. AB - This report documents our experience with mitral valve replacement in children. Between 1978 and 1982, 30 replacements have been performed in patients under 15 years of age. Twenty seven patients (90%) with rheumatic heart disease and 3 (10%) had congenital disease. Their functional capacity prior to operation was as follows: Nine patients fell into class II, 18 into class III and 2 into class IV. Preoperative cardiac catheterization, was undertaken in 26 patients, the mean pulmonary arterial wedge pressure was 27.4 +/- 8 mmHg, the pulmonary artery mean pressure was 48 +/- 20 mmHg, the left ventricular end diastolic pressure was 11.7 +/- 5.6 mmHg. One child died in the operative period. Twenty six patients (90%) have been followed for a mean period of 22.7 months. Late mortality occurred in three patients (11%). Bacterial endocarditis, thromboembolism and valve maldisfunction were not present. The post operative NYHA functional class was as follows: twenty two children fell into class I, and one patient fell into class II. The actuarial survival rate 5 years after operation was 79%. We believe that the Bjork-Shiley prosthesis offer excellent results in children when repair of the natural valve is not possible. PMID- 6241462 TI - [Chagasic heart disease in Mexico. 1st case diagnosed by positive xenodiagnosis]. AB - We describe the first case of chronic Chagas heart disease in Mexico, in whom the illness was corroborated by means of the "xenodiagnosis". The patient had changing bundle branch block and also A-V block that required insertion of a pacemaker. This disease is seldom seen in Mexico. PMID- 6241463 TI - [Effects of orthostatism on heart rate and arterial pressure in sedentary subjects and in those in good physical condition]. AB - Heart rate (HR), Systolic (SBP), Diastolic (DBP), and Mean Blood Pressures (MBP), were evaluated during a resting sitting and during upright moveless positions, in fifty seven highly trained runners with a maximal oxygen consumption equal or superior to 55 ml/kg. min. (VO2 max greater than or equal to 55 ml/kg . min., group I), and in fifty seven sedentary untrained men (group II). During sitting position the members of group I, had a significantly lower DBP and MBP than the members of group II. In the members of group II the assumption of upright posture did not produce significant changes in blood pressure, whereas subjects of group I showed a significantly drop in SBP, DBP and MBP. The results of this investigation indicated that in human, vigorous physical activity produce lower values of arterial blood pressure, and might be of value in the prevention of high blood pressure. On the other hand, the observed responses in group I during orthostatism, reveal a different regulation of the cardiovascular system. Changes in sympathetic and parasympathetic nervous system, venous compliance and plasma volume are designated as responsible of observed differences. This finding might also support the tendency to faintness reported by some authors in athletes. PMID- 6241464 TI - [Marfan syndrome and echocardiography]. AB - We report the echocardiographic features of nine patients with Marfan syndrome. Six men and three women. Average age: twenty nine years. Sixty six per cent had aneurysmatic enlargement of the aortic root. One hundred per cent of the cases had aortic insufficiency, enlargement of the left ventricular diameter, decrease of the ejection fraction, and decrease in circunferential shortening; mitral prolapse, (in 6) and signs of high pulmonary artery pressure (in 4 cases). Hemodynamic studies performed in 46 per cent of the patients correlated well with the echocardiographic features. Autopsy performed in the patients who died, corroborated the cardiovascular abnormalities. We conclude that the use of the echocardiogram is a useful non-invasive technique for the early evaluation of the cardiovascular features in the Marfan syndrome. PMID- 6241465 TI - [Automatism: an intrinsic property of cardiac tissues]. AB - Automaticity is an intrinsic property of some types of cardiac tissues, like the nodes and the conducting fibers. Automatic cells are characterized by the appearance, during diastole, of a slow depolarization which is capable of reaching threshold and generate an action potential. This depolarization is the so-called slow diastolic depolarization, or pacemaker potential. Tissues with automaticity do not have the same intrinsic firing frequency, which determines the existence of a true pacemaker; normally this role is assumed by the sinus node and several latent, or subsidiary pacemakers. The latter do not give any manifestation, because, since they have a slower firing frequency than that of the true pacemaker, the impulses generated by the latter will activate them before they can reach threshold. The ionic mechanisms that originate the pacemaker potential are just some of the processes that constitute the electrophysiological properties of the cardiac cell membranes. The mechanism includes the slow inactivation of an outward current combined with a constant inward current. Recently published evidence suggests that the pacemaker potential could be the resultant of an inward current that is slowly activated during the final part of the repolarization, but these data are still controversial and difficult to interpret. The factors that regulate heart rate modify the electrophysiological characteristics of the membrane by means of three major mechanisms: the slope of the pacemaker potential, the voltage of the threshold potential and, the maximum diastolic potential. Some of the most important factors that modulate heart rate include the neurotransmitters of the automatic nervous system, the plasmatic levels of some ions, like potassium and calcium, and changes in the intrinsic properties of the membrane, like the influence of heart rate on the activity of the sodium pump. PMID- 6241466 TI - [Evaluation of pulmonary arterial hypertension by phonoechocardiography and Doppler]. AB - We discuss the value of the non-invasive methods such as phonomecanocardiography, echocardiography and Doppler in the assessment of pulmonary arterial hypertension (PAH) The phonocardiographic record, the yugular phlebogram and the precordiogram, have a good correlation with the systolic pressure of the pulmonary artery. The two-dimensional echocardiogram is the technique of choice to determine the state of the pulmonary artery bandages after surgery and is also useful in cases of pulmonary thromboembolisms. The most reliable non-invasive method to determine the severity of the PAH is the Doppler study of the outflow tract of the right ventricle and pulmonary artery. PMID- 6241467 TI - [Influence of sympathomimetic drugs on immediate intradermal reactions induced by allergens]. PMID- 6241468 TI - The Pk-3 gene determines both the heart, M1, and the kidney, M2, pyruvate kinase isozymes in the mouse; and a simple electrophoretic method for separating phosphoglucomutase-3. AB - We have found that in mice carrying Pk-3r, an allele leading to loss or activity of kidney pyruvate kinase, the activity of heart pyruvate kinase is also diminished. Electrophoretic studies on tissues from mice carrying Pk-3r and/or Pk 3b, an allele determining an electrophoretically detectable variant, show that Pk 3 affects the expression of both the heart, M1, and the kidney, M2, pyruvate kinase isozymes. These results, together with linkage data, indicate that both isozymes are determined by the same structural gene, Pk-3. We also report a simple method for separating phosphoglucomutase-3 (PGM-3) by electrophoresis on cellulose acetate plates. PMID- 6241469 TI - Influence of B and Pl on UDPG:Flavonoid-3-O-glucosyltransferase in Zea mays L. AB - The influence of the genetic constitution at the B and Pl loci on UDPG:flavonoid 3-O-glucosyltransferase activity is described. More than a 90% reduction in activity is found when either B or Pl was present in the homozygous recessive condition. A positive correlation between quercetin-3-O-glucoside and pelargonidin-3-O-glucoside production is observed for all genotypes tested. Changes in UFGT activity during plant development are described for R-r B Pl plants. PMID- 6241470 TI - Analysis of decreased autologous mixed lymphocyte reaction of cord blood lymphocytes: with special reference to production of and response to interleukin 2 (IL-2). PMID- 6241471 TI - Changes in delayed-type hypersensitivity and helper function activities of T cell lines and clones during long-term culture. PMID- 6241472 TI - [Elimination of endemic goiter in students in the Lerma valley, Salta, Argentina]. PMID- 6241473 TI - [Prescription and dispensation of sulfonamides, urinary antiseptics and antiparasitics in Concepcion, Chile]. PMID- 6241474 TI - [Diagnosis and treatment. What do patients know?]. PMID- 6241475 TI - [Anthrax in 2 communities in Zacatecas, Mexico]. PMID- 6241476 TI - [Multidisciplinary focus for health research in Cuba]. PMID- 6241477 TI - Alternatives to amalgam alloys: 1. PMID- 6241478 TI - Competition between anaerobic covalent linkage of neocarzinostatin chromophore to deoxyribose in DNA and oxygen-dependent strand breakage and base release. AB - Treatment of poly(dA-dT) X poly(dA-dT) with the nonprotein chromophore of neocarzinostatin in the presence of sulfhydryls resulted in both direct and alkali-dependent base release, indicative of DNA sugar oxidation. Covalent chromophore-DNA adducts were also formed. Under anaerobic conditions, base release was strongly inhibited; however, adduct formation was not inhibited and in some cases was markedly enhanced. In the presence of dithiothreitol, anoxia increased adduct formation by a factor of 2, and a particularly stable adduct species was formed, which was recovered from nuclease digests of the treated DNA as a highly fluorescent compound with structure chromophore-d(TpApT). Acid hydrolysis of chromophore-d(TpApT) released free adenine base and both 3'dTMP and 5'dTMP, leaving a compound that contained only chromophore and the deoxyadenosine sugar. These results conclusively confirm that the chromophore forms a covalent adduct with deoxyribose in DNA. Thus, even in the absence of oxygen, activation of the chromophore by sulfhydryls results in the formation of a species capable of reacting with deoxyribose. Several other adduct species were also formed, some of which were nonfluorescent and relatively hydrophilic, but all of which were produced in increased amounts under anoxia. This inverse relation between sugar oxidation and adduct formation suggests that the two lesions share a common precursor. In the presence of other thiols, the effects of anoxia were somewhat different. With glutathione, anoxia markedly enhanced adduct formation, but the total adduct formed was considerably less than with dithiothreitol. With 2 mercaptoethanol, anoxia had no effect on total adduct formation, but the distribution of adduct species was altered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 6241479 TI - Chemical evidence for probably nonequivalent beta subunits in F1 adenosinetriphosphatase. AB - Mitochondrial F1 adenosinetriphosphatase (MF1) was allowed to react with 7-chloro 4-nitro-2,1,3-benzoxadiazole (NBD-Cl) until its NBD label to MF1 molar ratio (n) reached approximately 2.6. The labeled enzyme was then separated and subsequently allowed to react with dithiothreitol (DTT) in a controlled way to have its covalent label partially removed. At various stages of removal of its covalent label, the enzyme was separated and assayed for its value of n and the ratio (r) of specific ATPase activity of the DDT-treated enzyme to that of the unlabeled control sample. Most of the experimental values of r turned out to be significantly higher than the theoretical maximum values for models of the enzyme with three equivalent beta subunits, which have been shown to be equal to (1 - n/3)3 for three alternating sites and (1 - n/3)2 for two alternating sites. On the other hand, the observed values of n and r are consistent with a model of the enzyme based on nonequivalent beta subunits, with one active catalytic site and two latent catalytic sites that normally have only regulatory function. Possible complication in the interpretation of data due to a significant amount of nonspecific labeling by NBD-Cl has also been examined and discussed. In addition, the NBD label has been used, after its transfer from the essential Tyr to the essential Lys, as an internal fluorescent probe to monitor protein conformation change at the active site of MF1. Experimental data show that the binding of adenine nucleotide at the latent site(s) can cause conformational change at the active site and presumably in this way regulate the catalytic property of the active site. PMID- 6241480 TI - Evidence for a nucleotide binding site on the isolated beta subunit from Escherichia coli F1-ATPase. Interaction between nucleotide and aurovertin D binding sites. AB - The nucleotide binding capacity and affinity of the isolated beta subunit from Escherichia coli F1-ATPase have been studied with radiolabeled ADP and ATP by an equilibrium dialysis technique. Each mole of beta subunit in the presence of EDTA bound 1 mol of ADP or ATP with Kd values of 25 microM and 50-100 microM, respectively. At a saturating concentration, aurovertin enhanced the affinity of ADP or ATP for the isolated beta subunit by 3-6-fold. The Kd values for the binding of ADP or ATP were also assessed through the enhancing effect of ADP on [14C]aurovertin binding (Issartel, J.-P., Klein, G., Satre, M., & Vignais, P.V. (1983) Biochemistry 22, 3485-3492); the Kd values determined by this approach were several times lower than in the absence of aurovertin, in agreement with results obtained by direct titration with radiolabeled ADP or ATP. PMID- 6241481 TI - Cloning and expression in Escherichia coli of the TL-DNA gene 4 of Agrobacterium tumefaciens under the control of the PR promoter of bacteriophage lambda. AB - A plasmid was constructed that directs expression of the TL-DNA gene 4 protein in E. coli. The different steps of the construction were as follows: i) a region of gene 4 encoding the amino-terminal portion of the protein was fused in frame to DNA encoding an enzymatically active carboxy-terminal fragment of beta galactosidase. The hybrid gene was poorly expressed from the upstream lambda PL promoter carried by the vector. ii) in order to generate an efficient procaryotic ribosome binding site, a DNA fragment carrying the lambda PR promoter with the nearby Shine-Dalgarno (SD) sequence of gene cro was placed in front of the gene 4 lacZ fusion. A recombinant plasmid, termed pGV793, that expressed efficiently a fused protein 4-beta-galactosidase was identified among the Lac+ clones. DNA sequencing analysis showed that pGV793 carried a hybrid ribosome binding site composed of the cro SD sequence, a five bp sequence and the ATG codon of gene 4. Plasmid pGV793 directed the synthesis of three polypeptides of molecular weight 132 Kd, 126 Kd and 122 Kd that carried beta-galactosidase antigenic determinants. The largest polypeptide had the expected size for the hybrid protein. The fusion proteins which accounted for about 0.5% of the total cellular proteins were purified by immunoadsorption using anti-beta-galactosidase antiserum. iii) the complete gene 4 coding sequence was reconstituted, with the lambda PR promoter in place. The resulting pGV822 plasmid expressed a polypeptide whose molecular weight 27 Kd corresponded to the expected size for the gene 4 product. The pI was about 7. PMID- 6241482 TI - Immunocytochemical localization of beta-hexosaminidase and electron-microscopic characterization of human fibroblasts following treatment with monensin and nigericin. AB - Immunocytochemical localization of beta-hexosaminidase in cultured human skin fibroblasts was performed in the presence or absence of the Na+/K+ ionophores monensin and nigericin. In the presence of monensin, beta-hexosaminidase accumulated in the periphery of swollen vesicles in the paranuclear region of fibroblasts from normal individuals and from patients with mucolipidosis II. Nigericin-treated cells had more extensive vacuolization of the cytoplasm and the localization of the enzyme was more diffuse within these vacuoles. Morphological studies at the ultrastructral level indicated that a perturbation of the Golgi region occurred during ionophore treatment. These findings suggest that beta hexosaminidase in ionophore-treated fibroblasts is trapped in a time- and dose dependent manner in the paranuclear region presumed to be the swollen cisternae of the Golgi region, or adjacent vesicles derived from the Golgi region. Furthermore, fibroblasts are more sensitive to perturbation by nigericin than by monensin at similar concentrations and exposure times. These data support biochemical findings that the two ionophores differentially inhibit the transport of lysosomal enzymes in the Golgi region. PMID- 6241483 TI - Correlation between changes in cell adhesion and the ratio of N- to O-linked glycopeptides during chick embryo development. AB - After treatment with trypsin, chick embryo fibroblasts exhibited an age-related difference in their capacity to readhere to the substratum, since 8-day-cells readhered more rapidly than 16-day-cells. Treatment with tunicamycin altered embryo cell readhesion to the substratum in varying degrees, depending on the duration of drug treatment and of readhesion assay. The effect of tunicamycin was not toxic and was totally reversible with time after its removal. These results indicated that embryo cell readhesion involved trypsin-sensitive cell surface glycoproteins. During embryo development, the glycosylation of cell surface glycoproteins altered markedly. The ratio of N-linked to O-linked glycan chains dropped from 80/20 in 8-day-cells to 55/45 in 16-day-cells, indicating that the relative labelling of O-linked glycan chains increased during embryo development. This result was confirmed by alkaline treatment of radiolabelled glycan chains, and by the fact that tunicamycin treatment reduced 14C-glucosamine incorporation by greater than or equal to 80% in 8-day-cells but only 60% in 16-day-cells. Marked changes were observed during embryo development in the structure of the N linked glycan chains; concanavalin A-Sepharose chromatography showed that these changes concerned the glycopeptides containing complex type carbohydrate chains. The ratio of tri- plus tetra-antennary chains to bi-antennary chains increased about 2.5-fold between the 8th and 16th day of development. A correlation was noted between embryo cell readhesion to the substratum and N-glycosylation of cell surface glycoproteins. The N-linked glycoconjugates played a crucial part in cell readhesion. The possible role of O-linked structures in such readhesion is discussed. PMID- 6241484 TI - Specific binding and biological effects of tumor promoting phorbol esters on sponges. AB - Sponges grown in the presence of 12-O-tetradecanoyl phorbol-13-acetate (TPA) show deep alterations of their structure and development. Their aquiferous system (flagellated cells and canals) is largely altered and the tissues show an unusually high cell density. This focalized effect of TPA on the aquiferous system seems specific and is reversible at low concentrations (100 ng/ml). A toxic, non-specific effect is also noted, particularly at high concentrations (5000 ng/ml). Using 3H-phorbol-12, 13-dibutyrate (3H-PDBu), we demonstrate a class of specific binding sites for phorbol esters in the homogenates of sponges. These binding sites have high affinity (Kd = 26.0 nM) for PDBu and at saturation about 20 pmoles of 3H-PDBu is bound per mg protein of sponge homogenates. The binding of 3H-PDBu was inhibited by other phorbol esters and their congeners, and there was a good correlation between their potency in binding inhibition and their tumor promoting activity. It is concluded that sponges have a class of specific saturable and high affinity receptors for phorbol esters and that there is a very high conservation of these receptors during evolution. Such specific binding may be responsible for subsequent biological effect of TPA on sponges. PMID- 6241485 TI - [Study of a lysis medium stabilizing microfilaments and microtubules in vitro and in vivo]. AB - Determination of experimental conditions which allow the evaluation of the variations in the ratio of non polymerized and polymerized forms of actin and tubulin during the reorganization of the cytoskeletal cell system is of most valuable importance. In order to prepare cell homogenates which would reflect the in vivo situation, we tested in vitro a lysis medium which stabilized both microfilaments and microtubules, which were determined by DNase inhibition assays and colchicine binding assays respectively. This lysis medium containing 10 mM potassium phosphate, 1mM magnesium chloride, 5 mM EGTA, 1 M hexylene glycol, 1% Triton X-100, pH 6.4, used at 4 degrees C a) diffused rapidly into the cells; b) did not denature actin and tubulin; c) did not displace the equilibrium between non polymerized and polymerized forms of actin and tubulin, allowing biochemical assays on cell homogenates; d) blocked the evolution of the cytoskeletal system and permitted structural studies; e) and allowed the decoration of microfilaments by heavy meromyosin. PMID- 6241486 TI - Effects of an extract of human brain containing growth factor activity on the proliferation of human vascular endothelial cells in primary culture. AB - Lesions of vascular human EC play an important role in the development of thrombi and atherosclerosis. The factors which control the repair of vascular lesions are not well known. In addition, they are difficult to study because vascular EC from large vessels are fastidious cells to grow in tissue culture. We have investigated some of the factors that may be important in human umbilical vein EC growth in primary culture. Because of reported species differences in EC culture, we have decided to culture human EC only in the presence of biological culture reagents of human origin. Human umbilical vein EC, at low seed density, can be grown to confluency on a human FN matrix or on human ECM providing the medium is supplemented with a high concentration (30%) of human serum. The optimal proliferation of EC (even when seeded at clonal density) is obtained if HBE is added. HBE cannot completely replace serum, but EC proliferate to a similar extent whether they are grown on FN or on ECM in the presence of 30% human serum of 10% human serum plus HBE. Thus, HBE contains a growth factor activity for human EC which stimulates cell growth and DNA replication. Further work is needed to purify HBE and to compare it to other endothelial cell growth factors isolated from bovine brain and bovine eye. PMID- 6241487 TI - Testosterone-induced nuclear changes in the rat uterine luminal epithelium. A stereological study. AB - Testosterone administration to the spayed immature female rat produces significant changes in the nuclear ultrastructure of the uterine epithelial cells. In general, these changes increase when a higher dose is used. The most intense changes occur in the nucleolus: volume density and volume increase; volume increases in all nucleolar compartments; granular and vacuolar volume density increase; fibrillar center number increase, but a reduction of their individual volume is observed. Condensed chromatin volume density and volume decrease. Nuclear volume, nuclear envelope surface, and nuclear body volume density and frequency remain almost the same. The surface density of the interface between condensed and dispersed chromatin, fibrillar centers and fibrillar component, and condensed chromatin and fibrillar component, show significant variations even with a small dose of testosterone (0.5 mg). Such a dose is unable to change the volume density of condensed chromatin or fibrillar centers. Correlations between our results and biochemical or other morphological data are discussed. PMID- 6241488 TI - Pituitary adenomas: patterns of hPRL and hGH secretion as revealed by high resolution immunocytochemistry. AB - Seven human pituitary adenomas obtained by transphenoidal surgery were investigated for the intracellular localization of PRL and GH, using the protein A-gold immunocytochemical technique. Among the seven cases two were prolactinomas, two were GH-secreting adenomas and three were mixed PRL and GH secreting adenomas. When PRL or GH were revealed, immunoreactivity was found in the cellular compartments involved in protein secretion, RER, Golgi apparatus and secretory granules of corresponding secreting cells. An increasing gradient in the intensity of labeling was observed from the RER to the Golgi and to the granules which may correspond to the increasing concentration of the proteins occurring along their secretory pathway. In addition, crinophagy or destruction of secretory granules by the lysosomal system was observed for both secretory cells. Cells displaying simultaneously PRL and GH reactivity were never found, neither in pure nor in mixed adenomas demonstrating that in the different adenomas studied, secreting cells have retained their specificity and differentiation for the secretion of a single hormone. PMID- 6241489 TI - Localization of thymulin (FTS-Zn) in mouse thymus. Comparative data using monoclonal antibodies following different plastic embedding procedures. AB - The distribution of thymulin (FTS-Zn) was studied in thymuses from normal mice (OF1) or autoimmune mice (NZB). Thymulin localization was investigated using immunocytochemical techniques on sections of GMA and epon-embedded mouse thymuses. Two monoclonal antibodies were used: anti-synthetic thymulin and anti intracellular thymulin. In the immunofluorescence assay, GMA sections allowed a more subtle localization of thymulin in the cytoplasm of epithelial cells (with a vacuolar pattern) compared to the epon sections (with a homogeneous fluorescence in the cytoplasm). In both cases, the number of labeled cells was greater in the medullary region than in the cortex of the thymus. At the electron microscopic level, immunolabeling of epon ultrathin sections showed ferritin distributed in some of the epithelial cell vacuoles. The two monoclonal antibodies revealed similar distributions of thymulin in the thymus. The results obtained in this study confirm that the amount of thymulin is greater in the epithelial cells of normal compared to autoimmune thymuses. PMID- 6241490 TI - Changes in organization and microtubule assembly activity of the centrosome during lymphocyte stimulation. AB - Changes in the organization of centrosomes in mouse splenic T lymphocytes stimulated by concanavalin A (con A) were examined by electron microscopy of serial sections. In both resting and stimulated lymphocytes the single centrosome consists of a pair of centrioles, satellite bodies, and pericentriolar material. In resting cell centrosomes the satellite bodies are preferentially associated with, and appear to be attached by short stalks to, one of the centrioles. The satellite bodies are the primary sites of microtubule termination in the resting cell centrosome. During stimulation by con A there is a several-fold increase in microtubule content. This is correlated with an overall increase in centrosome size, an apparent increase in the size and in the number of satellite bodies, and a redistribution of satellite bodies to occupy a position between the two centrioles. Increased numbers of microtubules are detected terminating on the satellite bodies and in the pericentriolar material of the stimulated cell centrosome. Microtubule assembly from centrosomes in vitro was assessed by electron microscopy using detergent-permeabilized lymphocytes that had been pretreated to remove endogenous microtubules and supplied with purified bovine brain tubulin. These studies indicate that satellite bodies are major sites of microtubule assembly in both resting and stimulated cell centrosomes and show that the centrosomes of stimulated cells assemble more microtubules in vitro than resting cell centrosomes. This parallels the increase in microtubule content in intact lymphocytes stimulated by con A and suggests that the changes in centrosome organization and microtubule assembly capacity that occur during stimulation are causally related. PMID- 6241491 TI - Relationships between cytoplasmic microtubular complex, DNA synthesis and cell morphology in mouse embryonic fibroblasts (effects of age, serum deprivation, aphidicolin, cytochalasin B and colchicine). AB - Aging, aphidicolin, serum deprivation and cytochalasin B induce a decrease in the rate of DNA synthesis, an increase in cell flattening (cell surface increase) and an extension of the cytoplasmic microtubular complex (CMTC). Age and experimental conditions affect the protein content of the cell, but there is no relationship between cell morphology and cell protein content. Serum deprivation, aphidicolin and cytochalasin B are more effective on DNA synthesis and cytoplasmic actin complex (CAC) of late than of early fibroblasts. Despite these facts, the cell morphology of late cells is fairly stable and is not affected by experimental conditions, which exert an "aging effect" upon the cell morphology in earlier cultures. Colchicine acts upon the CMTC, cell morphology and DNA synthesis at all ages of the cultures. It also induces disruption of the CAC, the intensity of the disruption depending on both the length of the treatment and the age of the culture: the sensitivity of the actin-microfilaments to colchicine increases with the mitotic age of the cells. We suggest that the microtubular integrity is needed, but not sufficient, to preserve the organization of the CAC into microfilaments. We propose a logical model comprising feedback loops between the number of the mitotic cycles, the rate of DNA synthesis, the extention rate of the plasma membranes and CMTC in normal fibroblasts. CMTC is associated, in this model, with the expression of negative or positive controls, depending on the grade of its extension (Fig. 9). PMID- 6241492 TI - Slanted centriole and transient anchoring apparatus during spermiogenesis of an Oligochaete (Annelida). AB - An electron microscopic analysis of Tubifex tubifex (Annelida, Oligochaeta) spermiogenesis has revealed the presence of a slanted basal body during the early stages: the centriole has the shape of a cylinder obliquely cut at one extremity. In these stages an anchoring apparatus is also present, similar to the one of primitive spermatozoa, and disappearing in the mature sperm. The slanted centriole in cross section gives images of "incomplete" centrioles similar to the ones reported in the literature and interpreted as images of centriologenesis. The transient anchoring apparatus is interpreted as a rudimentary organelle used during spermiogenesis to maintain the centriole in a correct position. This function in the mature spermatozoon is performed by the mitochondria. PMID- 6241494 TI - [Societe de Biologie Cellulaire de France. 2d annual convention. Paris, 17-19 September 1984. Abstracts]. PMID- 6241493 TI - S-antigen immunoreactivity in retinal rods and cones and pineal photosensitive cells. AB - The S-antigen is a protein of photoreceptors, mainly known for its autoantigenic properties in mammals, which is widely distributed in the retina of vertebrates and in photoreceptor organs of invertebrates. Using three monoclonal antibodies specific for different epitopes of S-antigen, this study complements our previous data on retinal rods and cones and presents new results on the photosensory cells of the pineal complex. Immunoreactivity was found in (i) retinal rods and cones, (ii) cone-like and modified photoreceptor cells, and pinealocytes of the pineal organ of vertebrates, (iii) cone-like photoreceptors of the frontal organ of the frog and of the third eye of the lizard. According to the species and the antibody used, some differences were found at the level of the cellular compartments of the pineal photoreceptor cells. PMID- 6241495 TI - Anchorage of the nucleolus in the pore complex-lamina by a DNA-bearing structure masked in situ in rat liver nuclei. AB - We have developed a method by which nuclear shells containing nucleoli can be isolated from membrane-depleted rat liver nuclei. This method involves the removal of the internal chromatin. This chromatin is expelled from the nuclear shell using combinations of low and high ionic strength buffers. The expelled internal part is subsequently digested with DNase I or micrococcal nuclease. Examination by electron microscopy of the nuclear and the nucleolar structures at various steps of the isolation procedure shows that the nucleoli are anchored in the peripheral lamina by a pedicle that is continuous with an intranucleolar network. This network is masked in situ by nucleolar granules. The pedicle and the network which support the nucleolar DNA are composed mainly of non-histone proteins insoluble in 2M NaCl. PMID- 6241496 TI - [Identification of anesthetics and adjuvants by infrared and ultraviolet spectrophotometry]. PMID- 6241497 TI - [Oxygen-nitrous oxide mixing flowmeter with safety feature]. PMID- 6241498 TI - [To diminish the anesthetic risk tied to the use of nitrogen oxide]. PMID- 6241499 TI - [Combined flunitrazepam-fentanyl and curare in emergency internal surgery]. PMID- 6241500 TI - Preservation of ischemic myocardial tissue with an antagonist of vasoconstrictor eicosanoids. AB - A new antagonist of the vasoconstrictor eicosanoids, L-640,035, was studied in a standardized model of myocardial ischemia (MI) in anesthetized cats. This eicosanoid antagonist was not found to exert any overt hemodynamic action in cats subjected to a sham myocardial ischemia protocol. However, the antagonist markedly reduced the S-T segment of the electrocardiogram when administered 30 min after permanent occlusion of the left coronary artery. Moreover, circulating activities of the marker enzyme creatine kinase (CK) were markedly attenuated by L-640,035 3-5 h after the onset of MI. This was verified by cardiac biopsies 5 h post-MI since myocardial CK activities decreased much less in treated MI cats than in MI cats receiving only the vehicle for L-640,035 (i.e., ethanol). The active metabolite of the antagonist in biological fluids (i.e., L-636,499) markedly antagonized the vasoconstrictor actions of endoperoxide and thromboxane analogs, but not of noneicosanoids in isolated perfused coronary arteries. PMID- 6241501 TI - Regional isolation-perfusion: an experimental percutaneous approach tested and compared with arterial occlusion-infusion. AB - A percutaneous approach was developed for the performance of regional isolation perfusion, a surgical chemotherapeutic procedure for the intraarterial treatment of neoplasms. This technique was compared with percutaneous transcatheter arterial occlusion-infusion concerning local and systemic drug levels. Floxuridine (FUDR) was administered into a femoral artery of adult mongrel dogs, first by arterial occlusion-infusion, and 4 weeks later by regional isolation perfusion of the opposite hind limb. Local and systemic plasma samples and local muscle specimens were collected for determination of FUDR levels. Results indicated not only that regional isolation-perfusion could be accomplished percutaneously, using balloon catheters, but also that the technique produced significantly greater local tissue FUDR levels (P less than 0.05) than those achieved with arterial occlusion-infusion. PMID- 6241502 TI - Blind and target liver biopsy in the diagnosis of malignant liver diseases--a comparison. PMID- 6241503 TI - Small nuclear RNA-protein complex anchors on the actin filaments in bovine lymphocyte nuclear matrix. AB - When the nuclear matrix from bovine lymphocytes was digested by RNase-depleted trypsin, the bulk of the matrix proteins, except actin, were hydrolyzed. The digestion left rapidly sedimented spherical structures (trypsin-treated nuclear matrix), which mainly were composed of actin (Nakayasu, H. and K. Ueda. Exp. Cell Res. 143, 55-62, 1983). Almost all the small nuclear RNAs of the original nuclear matrix remained associated with these actin spheres after trypsin digestion. By sonication, the small nuclear RNPs (snRNPs) in both untreated and trypsin-treated nuclear matrices were solubilized in association with proteinous filaments of various size. The sedimentation pattern of these snRNP complexes was not changed by the digestion of the bulk of the proteins. The snRNP complex was adsorbed on rabbit muscle myosin-Sepharose then eluted by the addition of 5 mM ATP. We concluded that snRNPs are associated with actin filaments in the nuclear matrix of bovine lymphocytes. PMID- 6241504 TI - Heparan sulfate enhances growth of transformed human cells. AB - Previous studies showed that cell surface heparan sulfate (HS) is involved in density-dependent growth regulation of normal human cells. In this study the effects of HS on proliferation of transformed cells were studied in vitro. Exogenously added HS prepared from normal tissues (rat kidney and bovine kidney) enhanced growth of transformed human and animal cells (gamma ray- or virus transformed WI-38, and HeLa cells and chemically induced mouse hepatoma cells), but inhibited that of normal human and animal cells (WI-38, 3T3, and rabbit liver cells). HS was less effective on growth of both normal and transformed human cells at higher cell density. Although the exogenous HS did not bind to cells tightly, HS was found to affect cell growth not by modulation of growth-related substances in the medium, but through contact with the cell surface. HS preparation from tumour cells (mouse hepatoma cells) exerted similar effects on cell growth. Heparin, structurally similar to HS, inhibited growth of both normal and transformed human cells. These findings suggest that: 1. HS plays a particular function in contact regulation of cell proliferation. 2. Transformation-related changes in the structure of HS molecules do not much affect the function of HS. 3. The cellular transformation, however, is accompanied by alteration in the growth-regulating system sensitive to extracellular HS. PMID- 6241505 TI - Study of the in vitro activity of norfloxacin and other drugs on amoxicillin resistant uropathogenic isolates. AB - The in vitro activity of a quinolinecarboxylic acid compound, norfloxacin, was compared with those of amikacin, carbenicillin, cefazolin, cefoxitin, gentamicin, nalidixic acid, and oxolinic acid against 243 Gram-positive and Gram-negative amoxicillin-resistant (MIC 800 greater than or equal to micrograms/ml) uropathogenic isolates. Norfloxacin showed remarkable activity against the majority of the bacteria tested. Ninety percent of strains of Staphylococcus aureus, Streptococcus faecalis, Citrobacter freundii and Serratia spp. were inhibited by 3.12 micrograms/ml or less. Among the Gram-negative urinary isolates, only a few Enterobacter, Escherichia coli, Klebsiella, Proteus and Pseudomonas aeruginosa strains required norfloxacin levels between 12.5 and 25 micrograms/ml. The MBC was within one dilution of the MIC for 100% of the Gram positive strains and 95% of the Gram-negative isolates against norfloxacin and aminoglycosides. Norfloxacin had a markedly higher inhibitory index than all other antimicrobial agents for Gram-positive cocci and Gram-negative bacteria. From its in vitro activity, norfloxacin appears to be a potentially valuable agent for the treatment of serious urinary tract infections. PMID- 6241506 TI - Comparative in vitro activity of norfloxacin and four other chemotherapeutics against urinary gram-negative isolates. AB - Three hundred seventy-five Gram-negative bacterial strains were isolated from urine specimens of as many patients affected by symptomatic or asymptomatic urinary tract infections. Susceptibility of bacteria to five chemotherapeutics (norfloxacin, oxolinic acid, pipemidic acid, nalidixic acid and nitrofurantoin) was studied determining minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of each compound by a miniaturized dilution broth method. Norfloxacin, a quinoline carboxylic acid compound structurally related to nalidixic acid, showed a much higher antibacterial activity against all bacterial strains under examination including Pseudomonas sp. The best activity of norfloxacin was expressed either by lower MICs and lower MBCs with respect to those of the other compounds, or by a low MBC/MIC ratio, which represents an important advantage in clinical practice. PMID- 6241507 TI - Modulation of fluoropyrimidine cytotoxicity by methotrexate or 5 methyltetrahydrofolate in human leukemia cells in vitro. AB - The effects of methotrexate, 5-fluorouracil, 5-fluoro-2'-deoxyuridine on the growth of human leukemic T-lymphoblasts, CCRF-CEM, were determined as a function of drug concentration and exposure time. Substantial inhibition of cell growth (greater than or equal to 90%) was obtained with short duration of exposure (4 h) for MTX (ED90 = 4.3 microM). 5-fluorouracil was a relatively ineffective cytotoxic agent for exposure of short duration (4 h). Only exposure of 24 and 72 h resulted in cell growth inhibition greater than or equal to 90% with this drug. In terms of a ED90, 5-fluoro-2'-deoxyuridine was about 190- and 1300-fold more active than 5-fluorouracil for 24 and 72 h exposures, respectively (0.4 vs 75 microM and 0.01 vs 26 microM). Sequential exposure to methotrexate (4 h) and 5 fluorouracil during the last 2 h of methotrexate exposure resulted in synergistic inhibitory effects on cell growth. Antagonistic inhibitory effects on cell growth of methotrexate and 5-fluoro-2'-deoxyuridine combinations were observed independently of drug concentrations. Pretreatment (4h) with 5 methyltetrahydrofolate, the reduced folate to which leucovorin is rapidly converted in vivo, potentiated cell growth inhibitory effects of subsequently administered 5-fluorouracil or 5-fluoro-2'-deoxyuridine. These results provide information on scheduling of methotrexate or reduced folates and fluoropyrimidines that might have potential importance in the development of clinical trials designed for patients with leukemia and lymphoma. PMID- 6241508 TI - [General status and academic developments at the Chinese Medicinal Research Center]. PMID- 6241509 TI - [Progress in the research of deficiency-syndrome complexes and diseases of the aged in the past two years]. PMID- 6241510 TI - [Effect of an essence-restoring decoction on retarding the aging process--report of 62 cases]. PMID- 6241511 TI - [Effect of qing court shoutao pill in slowing down aging]. PMID- 6241512 TI - [Changes in the level of peripheral lymphocyte acid-naphthyl acetate esterase in patients with deficiency syndromes and its clinical significance]. PMID- 6241513 TI - [Effect of various herbs and acupuncture on Oddi's sphincter in the human]. PMID- 6241514 TI - [Effect of stimulating the neiguan point with a needle on hyperlipidemia- clinical analysis of 72 cases]. PMID- 6241515 TI - [Nail-fold and tongue-tip microcirculation in children with acute glomerulonephritis and treatment with huo xue hua yu]. PMID- 6241516 TI - [Therapeutic results in 529 cases of pneumonia in children]. PMID- 6241517 TI - [Anticonvulsants used for controlling induced seizures during the treatment of schizophrenia with lactoni Coriariae]. PMID- 6241518 TI - [Aplastic anemia treated with combined Chinese traditional medicine and western medicine--analysis of 46 cases]. PMID- 6241519 TI - [Treatment of chronic osteomyelitis with combined traditional Chinese medicine and western medicine--analysis of 104 cases]. PMID- 6241520 TI - [Biphasic regulating function of evil-dispersing drugs viewed from the effect of da cheng qi tang on vascular permeability]. PMID- 6241521 TI - [Development of a new phase in research of combined Chinese and western medicine on psychoses]. PMID- 6241522 TI - [Pharmacological effect of Puerarie thomsonii and its clinical use]. PMID- 6241523 TI - [Present status and prospect of research in traditional Chinese medicine and western medicine in life expectancy experiments]. PMID- 6241524 TI - [Sensory disease spreading along the nerve conduction route--report of 80 cases]. PMID- 6241525 TI - [Treatment of schizophrenia with a method of activating blood circulation and relieving stasis of the blood and changes in blood rheology]. PMID- 6241526 TI - [Short-term effect of 23 cases of leukopenia treated with Chinese huo xue hua yu drugs]. PMID- 6241527 TI - [Aplastic anemia treated with combined traditional Chinese and western medicine- clinical analysis of 52 cases]. PMID- 6241528 TI - [Renal disease and function of the spleen and stomach]. PMID- 6241529 TI - [Endoscopic studies of chronic atrophic gastritis before and after medical treatment--report of 60 cases]. PMID- 6241530 TI - [Treatment of allergic rhinitis by injecting Magnolia lilifora Desr. into the hypomucosa of the inferior turbinates]. PMID- 6241531 TI - [Treatment of nasal sinusitis with qin jie tang and changes in IgG levels]. PMID- 6241532 TI - [Relation between symptom-sign differentiation of diabetogenous bladder dysfunction and urine dynamics]. PMID- 6241533 TI - [Clinical analysis of 30 cases of glossy tongue and observations on the exfoliated cells of the tongue by imprints]. PMID- 6241534 TI - [Clinical and experimental study of the tongue in children with true or false symptom-complex]. PMID- 6241535 TI - [Treatment of cerebral thrombosis with Litsea cubeba (Zour) pers]. PMID- 6241536 TI - [Experimental research on the yin-yang theory of traditional Chinese medicine. I. Effect of monkshood, bark of the Chinese Cassia tree and Liu wei di huang fang on arterial pressure in the experimental hypertensive rat]. PMID- 6241537 TI - [Effect of extracts of radix Paeoniae rubrae and its derivatives on platelet aggregation and oxidative phosphorylation of mitochondria]. PMID- 6241538 TI - [Effect of alcoholic extract of prepared radix Polygoni multiflori on preventing atherosclerosis in Japanese quail]. PMID- 6241539 TI - [Treatment of functional uterine hemorrhage with combined traditional Chinese and western medicine]. PMID- 6241540 TI - [Problems of the co-application of Chinese drugs and western drugs]. PMID- 6241541 TI - [Pharmacological studies of a Chinese medicinal herb--Carthamus tinctorius]. PMID- 6241542 TI - Biologically active complement (C5)-derived peptides and their relevance to disease. AB - In man and in most mammals, activation of the complement system via either the classical or the alternative pathway results in the generation of biologically active peptides. The most active peptides are C5a and C5a des Arg generated by cleavage of the alpha-chain of native C5. C5a is a potent anaphylatoxin and can induce human polymorphonuclear leukocytes to migrate in a directed fashion, to degranulate, to undergo a burst of oxidative metabolism and to aggregate. Upon generation C5a is converted in serum and plasma to C5a des Arg with loss of the noxious anaphylatoxin activity. C5a/C5a des Arg play important roles in host defenses against bacterial infections and possibly in the mediation of some pathologic lesions such as the leukocyte infiltration seen in the lungs during acute respiratory distress syndrome. PMID- 6241543 TI - Congenital malformations in diabetic animal models--a review. PMID- 6241544 TI - Mechanisms of rat pancreatic islet allograft rejection. AB - Since the mechanisms of rat islet allograft rejection are unknown, metabolic, histologic, and immunologic parameters were characterized during rejection. Syngeneic intraportal islet transplants in diabetic Lewis rats normalize glucose values without islet cellular infiltrates; after Wistar-Furth allografts, glucose values rapidly return to diabetic levels and infiltration of islets by mononuclear cells occurs. Using lymphocyte proliferative assays, allogeneic islets induce a 3-fold stimulation of lymphocytes derived from nondiabetic allograft recipients. Using cytotoxicity assays, cell-mediated cytotoxicity of allogeneic islet target cells although inefficient is 2-fold greater in diabetic allograft recipients than in syngeneic recipients. Antibody-dependent cellular cytotoxicity is not observed, whereas 14 days after allotransplantation, complement-dependent antibody-mediated cytotoxicity is elevated. These data suggest that islet allograft rejection using metabolic, histopathologic and immunologic methods is associated primarily with cell-mediated cytotoxicity related to histocompatibility antigens. PMID- 6241545 TI - Immunomodulation of streptozotocin-induced diabetes in mice by a lipopolysaccharide. PMID- 6241546 TI - Effect of acid etching on the human tooth enamel: improvement of its clinical application. PMID- 6241547 TI - Biocompatibility test of microfilled resins and composites for core use in vitro. PMID- 6241548 TI - Mapping and properties of the gam and sot genes of phage mu: their possible roles in recombination. PMID- 6241549 TI - Analysis of the regulation of the transposition functions of bacteriophage mu by using gene fusions. PMID- 6241550 TI - Substrate and enzyme requirements for in vitro site-specific recombination in bacteriophage mu. PMID- 6241551 TI - Inversion of DNA in vivo and in vitro by gin and pin proteins. PMID- 6241552 TI - Comparative analysis of invertible DNA in phage genomes. PMID- 6241553 TI - Programming of DNA rearrangements involving mu prophages. PMID- 6241554 TI - RecF and RecBC function during recombination of nonreplicating, UV-irradiated phage lambda DNA and during other recombination processes. PMID- 6241555 TI - The mechanism of the chi-cos interaction in RecA-RecBC-mediated recombination in phage lambda. PMID- 6241556 TI - DNA interactions during bacteriophage lambda site-specific recombination. AB - Extensive research on site-specific recombination has provided many details, particularly with respect to the protein-DNA interactions. However, very little is known about the molecular mechanism of recombination during synapsis and strand exchange. Presumably, these steps of recombination involve various forms of DNA-DNA, DNA-protein, and protein-protein interactions. One stage at which DNA DNA interactions may be occurring is at the level of synapsis where the recombining DNAs are juxtaposed. In this paper we have presented evidence that homology-dependent DNA interactions do occur within the overlap region before strand exchange. This interaction is presumably at the synaptic stage of recombination. Furthermore, we have demonstrated that the homology-dependent interactions require that only one strand of attB have homology to attP. Another stage in recombination at which DNA-DNA interactions could occur is during strand exchange where complementary strands from the recombining parents are paired and resealed. We have also presented evidence that homology-dependent DNA interactions occur during strand exchange prior to the resealing of the strands and that disruption of this interaction results in nonreciprocal recombination. Taken together, these results suggest that DNA-DNA interactions during reciprocal site-specific recombination occur during at least two stages in the reaction. PMID- 6241557 TI - The role of specialized nucleoprotein structures in site-specific recombination and initiation of DNA replication. PMID- 6241558 TI - Lambda integrative recombination: supercoiling, synapsis, and strand exchange. AB - We have presented the first results of three ongoing experiments on the biochemical mechanism of lambda site-specific recombination. First, we have shown that under the tension induced by negative supercoiling, a segment of attP and attR undergoes a transition to a novel conformation. The basis for detecting this new structure implies that it contains unpaired bases, perhaps arising as a result of the transition of an inverted repeat to a cruciform structure. Since the segment undergoing transition lies outside the homologous core region, the unpairing of DNA that we have detected cannot be directly involved in synapsis. It will be of interest to learn whether recombination proteins alter this conformational change, possibly to extend its effect into the core region. Second, we have demonstrated that replacing phosphate groups in attachment site DNA with phosphorothioates interferes with recombination. Our first experiments indicate that the effect depends on locating phosphorothioates precisely at the site of recombination crossover. We take this to mean that interference is primarily at the step of breakage and reunion; we plan to exploit this inhibition in an attempt to trap synaptic intermediates in recombination. Finally, we have found that the rare cleavage of attP DNA by Int can involve either one or both strands of the duplex. This indicates that the degree of coordination between Int action at the two halves of the core region can be variable. Although we do not know whether this variability affects binding of Int, breakage of DNA, or resealing of broken strands, our data suggest that this variability can be regulated by sulfhydryl reagents. PMID- 6241559 TI - Effects of hormonal contraceptives on milk volume and infant growth. WHO Special Programme of Research, Development and Research Training in Human Reproduction Task force on oral contraceptives. AB - WHO conducted a three-centre study in Hungary and Thailand to evaluate the effects of hormonal contraception on lactation and infant growth. Women choosing oral contraceptives were randomly assigned to a combined oral contraceptive containing 30 micrograms ethinyl estradiol and 150 micrograms levonorgestrel (N = 86) or a progestin-only preparation containing 75 micrograms dl-norgestrel (N = 85). Identical packaging and treatment schedules allowed double-blind observation. One-hundred-and-eleven women using no contraception or non-hormonal methods acted as controls. In the two Thai centres 59 women using depot medroxyprogesterone acetate formed an additional comparison group. All subjects were healthy women with normal deliveries, whose infants had normal birth weights and satisfactory growth in the neonatal period. Breast milk volume was determined by pump expression using standardized procedures. Information was obtained on nursing frequency and supplementation, infant growth and morbidity. Pretreatment observations at 6 weeks post-partum were used as a baseline, and subjects were followed-up at 9, 12, 16, 20 and 24 weeks post-partum. Women using combined oral contraceptives had a decline in milk volume within 6 weeks of initiating treatment, whereas no significant decrease was observed in the other treatment groups. After 18 weeks of treatment, combined oral contraceptive users experienced a 41.9% decline in milk volume, compared to 12.0% with progestin-only minipills and 6.1% in the non-hormonal controls. The prevalence of complementary feeding and withdrawals due to inadequate milk supply were comparable in the four treatment groups. However, data were not available on the daily amounts of complementary feeds. There were no significant differences in growth of infants between treatment groups. Thus, women may have compensated for declines in milk volume by more supplementary feeding or by more prolonged and intense suckling episodes. We conclude that 30 micrograms estrogen-containing combined oral contraceptives impair milk secretion, but in the selected healthy group of mothers and children studied with the prevailing level of supplementary feeding, this did not adversely affect infant growth. PMID- 6241561 TI - Laparoscopic sterilization in a free-standing clinic: a report of 1,092 cases. AB - The five-year experience of 1,092 laparoscopic tubal sterilizations performed in a free-standing clinic in the U.S. with no anesthesiologist under local anesthesia is reviewed. The current technique of the Hasson "open" method and bipolar cauterization is felt to minimize major mishaps and is acceptably comfortable to the patient. PMID- 6241560 TI - Long-term follow-up of children breast-fed by mothers receiving depot medroxyprogesterone acetate. AB - A long-term follow-up study compared development and health of 128 breast-fed children whose mothers had received depot-medroxyprogesterone acetate (depot-MPA) while lactating and 142 control children whose mothers had used mechanical contraceptives or no contraceptives or had undergone sterilization. The children, who were approximately 4-1/2 years old at follow-up, showed no ill effects on their growth and development and health status from exposure to depot-MPA. Depot MPA-treated mothers lactated significantly longer than controls and also had greater parity than controls. These factors apparently contributed to a difference in weight at follow-up. Compared with the Sempe-Pedron standard, more of the depot-MPA group were underweight and more controls were overweight. PMID- 6241562 TI - Fibrinopeptide A plasma levels during low-estrogen oral contraceptive treatment. AB - In a group of healthy women taking oral contraceptives containing 30 micrograms ethinylestradiol combined with two different progestogens (desogestrel and gestoden), Fibrinopeptide A (FPA) plasma levels were evaluated both before and after 3, 6 and 9 months of therapy. FPA levels, which represent an index of thrombin action in vivo, were also determined in untreated subjects during the follicular and the luteal phases of the menstrual cycle. While no modifications of FPA levels were found during the menstrual cycle, a significant increase of this peptide was observed during oral contraceptive treatment. These data suggest that low-dose oral contraceptives, by enhancing the rate of conversion of fibrinogen to fibrin by thrombin, increase the risk of venous thrombosis. Since some mechanisms which compete with the thrombin activity are also increased by oral contraceptives, the significance of this change in the induction of thrombosis cannot be completely clarified. PMID- 6241563 TI - Tiapride versus placebo: a double-blind comparative study in the management of Huntington's chorea. AB - A double-blind, placebo-controlled, crossover trial was carried out in 29 patients with Huntington's chorea to evaluate the effectiveness and tolerance of high doses of tiapride in the management of neurological symptoms. Patients were allocated at random into 3 groups to receive 3 g tiapride daily for two periods of 3 weeks either preceded, interrupted or followed by a 3-week period on placebo. Patients were assessed on entry and at the end of each treatment period using a battery of tests designed to measure choreatic movements, motor skills, recognition and reaction times, and mental state. Twenty-three patients completed the trial; only 2 of the 6 drop-outs withdrew because of drug-related side effects (sedation and extrapyramidal signs). The results showed that tiapride treatment significantly improved choreatic movements and motor skills and these findings were supported by the objective psychometric measurements. Overall evaluation of effectiveness by the physician and patients indicated the significant superiority of tiapride over placebo. Treatment was generally well tolerated and although there were significantly more reports of sedation and extrapyramidal signs whilst patients were receiving tiapride, these effects were rated as mild in most cases and did not interfere with treatment. PMID- 6241564 TI - Mitral valve disease and dysphagia. AB - Eighty patients were studied to determine whether dysphagia (delayed transit through oesophagus) occurs in the presence of an enlarged left atrium. Twenty-six patients (group A), with no enlargement of the left atrium but undergoing open heart surgery, were randomly selected as controls. Group B (N = 54) consisted of patients undergoing mitral valve surgery with varying degrees of left atrial enlargement. All patients were requested to swallow, in the standing position, a barium filled capsule or barium filled Slow K tablets. If there was no hold up in the oesophagus the procedure was repeated with the patient seated. When hold up occurred the patient was screened at 5, 10 and 15 min. No hold up was found in any patient in the control group (N = 26). 50% of patients with left atrial enlargement had some degree of hold up, the incidence and duration of which correlated with the size of the atrium. Hold up was just as likely to occur with a capsule or with a 'slow K' tablet. When hold up lasted for more than 15 min, water did not flush away the 'stuck' medicament, but a bolus of solid food did. PMID- 6241565 TI - Competitive inhibition of [3H]spiperone binding to D-2 dopamine receptors in striatal homogenates by organic calcium channel antagonists and polyvalent cations. AB - The specific binding of [3H]spiperone (30 pM) to D-2 dopamine receptors in homogenates of the rat corpus striatum, as defined by the D-2 antagonist haloperidol (100 nM), was displaced by organic calcium channel antagonists and by polyvalent cations. Both classes of agents were able to totally displace [3H]spiperone binding by an apparently competitive mechanism in that the dissociation constant was increased while the density of binding sites was unchanged. The rank order of inhibition potency for the cations was Zn2+ greater than Cd2+ greater than La3+ greater than Cu2+ greater than Ni2+ greater than Co2+ greater than Mn2+ greater than Mg2+, Ca2+ greater than Ba2+. Of the organic calcium channel antagonists, D600 and verapamil were the most potent displacers of [3H]spiperone binding (IC50 values both 2.0 microM), while diltiazem possessed an IC50 of 33 microM. Nicardipine (IC50 6.0 microM) was the only 1,4 dihydropyridine to inhibit [3H]spiperone binding. The results suggest that sites labelled by [3H]spiperone also bind organic calcium channel antagonists and polyvalent cations. PMID- 6241566 TI - Perhexiline directly inhibits arterial myosin phosphorylation and stimulates cardiac myofibrillar ATPase activity. PMID- 6241567 TI - Identification of the enantiomers of SK&F 83566 as specific and stereoselective antagonists at the striatal D-1 dopamine receptor: comparisons with the D-2 enantioselectivity of Ro 22-1319. PMID- 6241568 TI - The involvement of subtypes of the 5-HT1 receptor and of catecholaminergic systems in the behavioural response to 8-hydroxy-2-(di-n-propylamino)tetralin in the rat. AB - The centrally active 5-HT receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) has a high affinity for the 5-HT1A subtype of the 5-HT1 recognition site in cerebral membranes and, in the rat, induces most aspects of the '5-HT behavioural syndrome' including hyperlocomotion, head weaving, a flat body posture and reciprocal forepaw treading. The mechanism of action of 8-OH-DPAT in producing these effects has been investigated. Consistent with an involvement of catecholaminergic neurons, reserpine dose-dependently reduced hyperlocomotion and head weaving, and most components of the syndrome were reduced by prazosin, haloperidol and sulpiride. However, reserpine did not block forepaw treading or the flat body posture, allowing pharmacological analysis of these behaviours in the absence of intact monoaminergic systems. Under these circumstances blockade by the selective 5-HT2 receptor antagonist, ketanserin, and by haloperidol was not seen, and only the flat body posture was significantly reduced by prazosin, rendering a key role for 5-HT2 receptors, alpha 1-adrenoceptors and dopamine receptors unlikely. In contrast, both behaviours in the reserpinised rat were inhibited stereospecifically by pindolol and by spiperone, which interact with 5 HT1 and 5-HT1A recognition sites. The residual behavioural effects of 8-OH-DPAT in reserpinised rats may, therefore, reflect the consequences of stimulation of the putative 5-HT1A receptor. PMID- 6241569 TI - A reduction of the tone of 5-hydroxytryptamine neurons decreases utilization rates of striatal and hypothalamic enkephalins. AB - The administration of drugs such as fenfluramine, p-chlorophenylalanine or 5,7 dihydroxytryptamine, which lower brain 5-hydroxytryptamine content, increases the enkephalin content of hypothalamus and striatum. None of these treatments changes proenkephalin mRNA content. On the basis of these results, we propose that 5 hydroxytryptamine does not increase the biosynthesis of enkephalin, but might increase the content of the neuropeptide by reducing peptide utilization. PMID- 6241570 TI - [Increasing survival of skin transplants by the treatment of transplants with hematoporphyrin derivative and visible light]. PMID- 6241571 TI - Lysosomal transport of cystine and other small molecules. PMID- 6241572 TI - Processing of precursors of mitochondrial proteins. PMID- 6241573 TI - The calelectrins: new and ubiquitous Ca2+-regulated proteins with a possible role in cytotic processes. PMID- 6241574 TI - Mechanisms of streptozotocin- and alloxan-induced damage in rat B cells. AB - In studies to evaluate possible inhibitors of the B-cell toxin, streptozotocin, the superoxide scavenger, superoxide dismutase, did not prevent or reduce the toxic effects of streptozotocin as determined by loss of insulin secretion from rat pancreatic B cells in monolayer culture. However, 1,1-dimethyl urea, a scavenger of the hydroxyl radical, did afford significant protection. Both scavengers diminished the cytotoxic effects of alloxan. The inhibitors of poly (ADP-ribose) synthetase, 3-aminobenzamide and nicotinamide, also were effective in attenuating alloxan- and streptozotocin-induced B-cell toxicity. Tests of the hydroxyl-scavenging ability of the three streptozotocin antagonists revealed that 3-aminobenzamide, nicotinamide and 1,1-dimethyl urea were effective scavengers of this free radical. Conversely, 1,1-dimethyl urea, although not as potent as 3 aminobenzamide or nicotinamide, was found to inhibit poly (ADP-ribose) synthetase. These data indicate that these chemicals most likely attenuate alloxan-induced toxicity by scavenging the hydroxyl radical and diminish streptozotocin-induced toxicity by inactivation of the poly (ADP-ribose) system. PMID- 6241575 TI - [Phage-typing in the surveillance of hospital infections: tests on strains of Staphylococcus aureus]. AB - The sensitivity of 44 coagulase positive Staphylococcus aureus strains to antibiotics has been determined. They have been isolated from in-patients and staff in a piedmontese hospital. It has been possible to obtain the phage typing of 26 of these strains: 4 have been attributed to group I, 3 to group II, 13 to group III and 6 to the "miscellanea". Some correlations have been established considering the data obtained by the laboratory and through epidemiologic research. PMID- 6241576 TI - [Dynamics of external respiration and gas exchange in combined body exposure to hypoxia and hypercapnia]. PMID- 6241577 TI - [Study of lymphocyte subpopulations in 2 cases of ankylosing spondylitis]. PMID- 6241578 TI - Isolation of sigma-28-specific promoters from Bacillus subtilis DNA. AB - Sigma-28-RNA polymerase is a minor form of RNA polymerase found in vegetative cells of Bacillus subtilis which utilizes promoter sites distinct from those recognized by the major RNA polymerase. We have isolated a collection of cloned B. subtilis DNA segments that contain in vitro promoter sites for sigma 28-RNA polymerase by screening a bacteriophage lambda library of B. subtilis genomic fragments. At least nine new sigma 28-specific promoter sites have been identified in this collection, and four have been partially mapped for further study. Our strategy employed a mix of RNA probes prepared by in vitro transcription with sigma 28-RNA polymerase of total B. subtilis DNA EcoRI and HindIII fragments. Over 70% of the unique clones identified contain sigma 28 specific promoter sites, suggesting that the method may have general application for identification of promoter-containing sequences. The efficiency with which sigma 28-specific promoters are detected is consistent with there being a relatively small number of such sites in the B. subtilis genome of which twelve have been cloned. PMID- 6241579 TI - CII-dependent activation of the pRE promoter of coliphage lambda fused to the Escherichia coli galK gene. AB - Using a cloning vector designed for the study of prokaryotic promoters by fusion to the Escherichia coli galactokinase gene (galK), we have constructed a plasmid in which the lambda pRE promoter controls galactokinase expression. A galK- host containing this plasmid has a Gal- phenotype since transcription from pRE requires activation by the lambda CII protein. When CII protein is provided by a prophage, galactokinase is synthesized at a rate dependent on the concentration of CII protein. A second plasmid was constructed in which the pRE promoter from phage 21 controls galactokinase expression. Transcription of the galK gene in this plasmid requires the phage 21 CII protein. Using this system, we demonstrate that the lambda and 21 pRE promoters are highly selective for their corresponding CII proteins. However, a cross-reaction between 21 pRE and the lambda CII protein was observed. In addition, we transferred the pRE-galK fusion unit from the plasmid to a phage, and then to the host chromosome in single copy. Galactokinase expression in this single copy pRE-galK system is also dependent on CII protein, which may be provided from a multicopy plasmid. The high concentration of CII protein provided by the plasmid results in maximal expression of the pRE-galK transcription unit. In this second system low levels of CII activity from CII- mutants are amplified and can be readily detected. PMID- 6241581 TI - Sequence analysis of a region from the early right operon in phage P22 including the replication genes 18 and 12. AB - A comparison of a 3000-bp sequence of Salmonella phage P22, coding for gene c1 and the replication genes 18 and 12, with the analogous cII-O-P region of coliphage lambda permits the localization of transcriptional signals, an oop RNA species, and the origin of replication (ori) within gene 18. Gene c1 and the amino terminal region of gene 18 show homology to the respective lambda genes. In the ori domain of the replicator proteins the homology to phi 82 is most pronounced. Of two lambda:repP22 hybrids (lambda with replication genes of P22) analysed, one codes for a hybrid O/18 protein with 30 N-terminal amino acids coded for by lambda. Gene 12 is nonhomologous to its lambda counterpart (gene P), but closely related to dnaB of Escherichia coli. A ren gene is missing, whereas two open reading frames (ORFs) distal to gene 12 are almost identical to those in the lambda nin region. We try to account for the occurrence and location of highly conserved sequences among the lambdoid phages by assigning them a role in recombinational reassortment of functional units during the evolution of this phage family. PMID- 6241580 TI - Molecular characterization of the qa-4 gene of Neurospora crassa. AB - The qa-4 gene of Neurospora crassa encodes 3-dehydroshikimate dehydratase, which catalyzes the third step of the quinic acid (qa) catabolic pathway. The enzyme has previously been purified and characterized as a monomer of approx. 37 kDal. The nucleotide sequence of the qa-4 gene is presented here and the amino acid composition and tentative NH2-terminal sequence confirm the identification of the coding region within the qa-4 DNA sequence. There are no introns in the qa-4 coding region. By S1 nuclease mapping and primer extension analysis three distinct regions of transcription initiation were identified. Heterogeneity was also observed in the 3' ends of qa-4 mRNA. 5' and 3' untranslated regions of the qa-4 gene were compared with the corresponding regions in other Neurospora genes. Genomic blot analysis of twenty previously isolated qa-4 mutants revealed that two mutants, MC150 and MC191, have restriction patterns altered from wild type. In each strain the alteration occurs in the 3' half of the qa-4 coding region. PMID- 6241582 TI - Structural organization of the ori site of phage P22; comparison with other lambdoid ori sites. AB - The homologous DNA regions of phages P22, lambda and lambdoid coliphages, which code for the amino-terminal portion of genes 18 or O, contain the ori signal. Both the lambdoid and P22 ori regions can be divided into sections, A, B and C. The four direct repeats with internal rotational symmetry of section A in P22 are less regularly organized than in the corresponding signals of the phi 80 and lambda ori sites and show greatest homology to coliphage phi 82. Section B is rich in adenines in the l strand, and section C can be recognized in the P22 ori by the occurrence of overlapping inverted repeats. The latter region is not homologous to the structurally similar section C, 'EcoRI-loop', of the lambdoid coliphages. The results further define the specificity determinants of lambdoid O protein-ori interactions and demonstrate the evolutionary relationship between these functional units. PMID- 6241583 TI - [Migration of Sr-90 and Mn-54 from soil and irrigation water to agricultural crops grown in different types of soil]. PMID- 6241584 TI - [Smoking as a negative health factor]. PMID- 6241585 TI - [Substantiation of measures for improving working conditions of postal workers]. PMID- 6241586 TI - [Working conditions and physiological reactions of adolescent machine operators during primary cotton cultivation]. PMID- 6241587 TI - The role of the Nursing Board of Hong Kong. PMID- 6241588 TI - [Cervical intradural-extradural neuroma--laminectomy and removal of tumor]. PMID- 6241590 TI - Paediatric CAPD in Hong Kong. PMID- 6241589 TI - Fluids, electrolytes and metabolic care of the paediatric patient. PMID- 6241591 TI - Short-course chemotherapy for tuberculosis. PMID- 6241592 TI - [The nature of the pancreas gland]. PMID- 6241593 TI - Florence NIghtingale, and Nursing in Hong Kong. PMID- 6241594 TI - Demographic trends of Down's syndrome in Egypt. PMID- 6241595 TI - Cell surface antigen marking the stages of murine T cell ontogeny and its functional subsets. PMID- 6241596 TI - Heterogeneity of accessory cells. PMID- 6241597 TI - Heterogeneity of macrophages and dendritic cells as accessory cells. AB - A number of different antigens was used to define the functional limits of Ia bearing murine dendritic cells and macrophages in the processing and presentation of antigens for T cell activation. The results show considerable functional overlap as well as differences attributable to known properties of the cells. Thus both cell types could present soluble antigens up to the size of polymeric flagellin (M.W. in millions) about equally well. The nonphagocytic dendritic cells were most effective at inducing mixed leukocyte reactions in accordance with their high constitutive level of Ia expression. On the other hand, splenic macrophages were three to nine times better than dendritic cells at presenting particulate, heat-killed Corynebacterium parvum organisms to T cells lines, and small activated macrophages from bone marrow cultures were three times better again than splenic macrophages. Large activated bone marrow macrophages were not effective antigen presenters probably because of nonspecific suppression. These observations are consistent with the phagocytic and lysosomal activities of macrophages that enable them to ingest and process particulate antigen efficiently. Nevertheless, the capacity of dendritic cells and the dendritic-like line, P388.AD.4, to present particulate bacterial antigens suggests that these cells could either do the processing extracellularly or pick up soluble antigenic moieties shed from the bacteria and antigen processing macrophages. Glutaraldehyde fixation of C. parvum presumably stopped antigen shedding, since it produced a greater reduction of the T cell response with dendritic cells and P388.AD.4 as presenting cells than with macrophage presenters. Alternatively, the fixation could make the bacteria less "digestible" to dendritic cells than to macrophages. More characterization of the fate of antigens following encounter with accessory cells is necessary to distinguish between these possibilities. PMID- 6241598 TI - The presentation of cell surface alloantigens to T cells. PMID- 6241599 TI - Accessory cells and T cell activation. The relationship between two components of macrophage accessory cell function: I-A and IL1. AB - Accessory cells are required for the activation of helper T cells. We have examined two characteristics of accessory cells, their expression of I-A, and their ability to release IL1. We provide evidence that these two properties are related, and postulate that membrane I-A molecules participate in the pathway leading to IL1-release. Experimental results are described relating I-A to IL1 release as follows: 1. In vitro-educated Ly1 T cells stimulate IL1-release from M phi; this process is H-2-restricted and blocked by anti-I-A antibodies. 2. H-2 restriction between T cells and M phi is overcome in the presence of ConA, but this unrestricted interaction is also blocked by anti-I-A. 3. LPS stimulation of IL1-release is blocked by anti-I-A. These findings suggested an active role for I A molecules on IL1-producing cells. We next describe a series of experiments designed to assess the requirements for I-A versus IL1 during T cell activation. In a number of experimental systems, T cells demonstrated a requirement for I-A recognition, but none that could not also be satisfied by IL1: 1. Generation of helper T cells in allogeneic chimeras. 2. Proliferation of KLH-primed lymph node cells. 3. Proliferation of KLH-primed lymph node cells from chronically anti-I-A suppressed mice. 4. Proliferation of GAT-primed lymph node cells from nonresponder mice. These findings suggest that for many kinds of T cells (not necessarily all) the apparent requirement for I-A-recognition is primarily involved in stimulating IL1-release from accessory cells. PMID- 6241600 TI - Selection of the delayed hypersensitivity T effector and T suppressor cell response by antigen-presenting macrophages. AB - The T effector lymphocytes of delayed type hypersensitivity reactions (TDH) are regulated by a complex T suppressor (Ts) cell circuit. Induction of TDH cells requires Ia+ adherent cells as antigen-presenting cells. Little is known about the antigen presentation of the induction of Ts cells. We describe an experimental model in which TDH and Ts cells are induced separately by different antigen-presenting macrophages grown from bone marrow stem cells. Bone marrow derived macrophages grown in L cell-conditioned medium for various periods and labeled with 2,4-dinitrobenzene sulfonic acid differ in their ability to induce TDH and Ts cells in vitro. The functional activity of the two T subpopulations was assessed in vivo by epicutaneous challenge or sensitization with 2,4 dinitrofluorobenzene of mice receiving the in vitro educated cells. Ear swelling or suppression of swelling was recorded. It could be shown that 5-7 day bone marrow-derived DNP-labeled macrophages preferentially induced Thy 1+ Lyt 1+ antigen-specific TDH cells; 7-10 day old antigen-presenting bone marrow-derived macrophages induced preferentially Thy 1+ Lyt 2+ antigen specific Ts cells. Characterization of various phenotypic markers revealed different surface antigen expression and functional differences such as MIF responsiveness or transglutaminase activity on the two macrophage populations. These data support the concept that activation of the Ts regulatory circuit may require antigen presentation by specialized antigen presenting cells, characterized by certain surface and functional markers and different from those inducing preferentially TDH cells. PMID- 6241601 TI - Macrophages as regulatory cells in mitogen induced spleen cell proliferation. 1. Macrophages as suppressor cells. AB - In this study the effect of alveolar (AC) or peritoneal (PC) lavage cells from Lewis rats on the mitogen induced proliferation of syngeneic spleen cells was investigated. When total spleen cells were stimulated with PHA (5 micrograms/ml) or ConA (6 micrograms/ml), the addition of AC or PC and of their adherent (A) or non-adherent (NA) fractions had dose dependent suppressive effects. After passing the spleen cells through a Sephadex G-10 column, the eluted cells responded poorly to the mitogens. Addition of low numbers (2 X 10(3) = 1%) AC or NA-AC improved this response, whereas higher concentrations (5 or 10%) of these cells or any concentration of A-AC, PC, A-PC or NA-PC showed either none or a suppressive effect. The cells which strongly suppress mitogen induced lymphocyte proliferation have macrophage morphology, are adherent, esterase positive, bear Fc receptor for IgG and bind ganglioside coated erythrocytes. NA-AC were further separated into Ia-depleted (Ia-) and Ia-enriched (Ia+) population. The Ia+ fraction contained 80 to 90% Ia bearing cells, supported the mitogen induced stimulation of Sephadex G-10 depleted spleen cells and was ineffective in suppression. Interestingly, these cells did not bind ganglioside treated sheep erythrocytes. On the other hand, the Ia-negative NA-AC fraction and particularly the A-AC population strongly expressed the "ganglioside receptor" as well as typical macrophage markers like Fc receptors, latex-phagocytosis and non-specific esterase. Therefore, the "ganglioside receptor" may be a useful marker to define suppressor macrophages. PMID- 6241602 TI - The antigen-presenting function of human Langerhans cells. PMID- 6241603 TI - The Langerhans cell, as a representative of the accessory cell system, in health and disease. AB - Cell surface receptors and antigens present on Langerhans' cells (LC) suggest a close relationship between LC and interdigitating cells (IDC) in lymph node sections or lymphoid dendritic cells (LDC) in cell suspensions. One of the reported differences is that Fc receptors (FcR) which are present on LC, are absent on LDC. This difference can at least partly be explained by a laboratory artefact: FcR on murine LC are irreversibly modulated by the Ig that contaminates the bovine albumin commonly used for gradients. Furthermore, the demonstration of FcR on murine LC requires prolonged exposure to EA at 4 degrees C. A significant percentage of nonadherent, low density, Ig- lymph node cells also express such FcR. These cells can stimulate syngeneic mixed lymphocyte reactions as can LC isolated from epidermis. Consideration of LC as cutaneous representatives of the accessory cell system led to an investigation of their numbers in epidermal sheets of patients with acquired immunodeficiency syndrome (AIDS). A marked reduction in Ia+, ATPase+, OKT6+ LC was found as compared to controls, suggesting that accessory cell deficiency may play a role in the extreme immunodeficiency seen in AIDS patients. PMID- 6241604 TI - Veiled cells--"dendritic cells" of the peripheral lymph. AB - The veiled cells (VC) of afferent lymph can be classified with dendritic cells (DC) of tissues on the basis of morphology, surface markers, cytochemical staining and function. VC form a population of cells, shown to carry antigens, in transit from the peripheral tissues to the paracortical areas of the lymph nodes. They can stimulate lymphocyte proliferation with antigens in vitro when added as less than 1% of the mononuclear cell population. They may initiate responses to foreign antigens such as keyhole limpet haemocyanin and 1-fluoro-2,4 dinitrobenzene (DNFB) and to alloantigen in the mixed leucocyte reaction or during grafting. VC may also be involved in antigen presentation in inflammatory and autoimmune diseases. PMID- 6241605 TI - Thymus independence, kinetics and phagocytic ability of interdigitating cells. PMID- 6241606 TI - [Thost-Unna syndrome. Clinical and therapeutic contributions]. PMID- 6241607 TI - [Phytophotodermatitis caused by fig tree]. PMID- 6241608 TI - [Our experience in the cure of rosacea with metronidazole]. PMID- 6241609 TI - Pathogenesis of meningitis: experimental studies on the molecular basis of Haemophilus influenzae infection. AB - The successful development and implementation of rational strategies for the prevention of bacterial meningitis should be facilitated by acquiring a more detailed knowledge of its pathophysiology. We have used a biologically relevant rat model of meningitis in conjunction with classical microbial genetics and recombinant DNA technology to investigate the molecular basis of Haemophilus influenzae pathogenicity. These studies aim to define how specific bacterial genes mediate the potential of H. influenzae to colonize the nasopharynx, disseminate within the blood stream and invade the central nervous system. By identifying the state or stages in the pathogenic sequence for which the determinant is critical, this approach should also provide insight into the relevant host defense mechanisms which determine resistance or susceptibility. An understanding of the genetic basis of H. influenzae pathogenicity may develop basic knowledge relevant to the treatment and prevention of bacterial meningitis. PMID- 6241610 TI - Relationship between radiological and clinical variables in spondylolysis. AB - A clinical and radiological follow-up investigation with at least 20 years observation time was made of 255 persons with lumbar spondylolysis with or without spondylolisthesis. The main purposes were to study the relationship between clinical and radiological features and to look for radiological and other variables of prognostic value. There was a clear positive correlation of symptoms and functional impairment during the observation period to disc degeneration and vertebral slipping at follow-up, as well as to a decrease in lumbar index at the time of diagnosis. Individual factors and radiological signs at the time of diagnosis were shown to have prognostic value for the course of the disease. The risk factors for severe symptoms and need for treatment were more than 10 mm of vertebral slipping, low lumbar index, increased lumbar lordosis, lysis in the fourth lumbar vertebra and early onset of symptoms. PMID- 6241611 TI - Workers' compensation. A psychiatric follow-up study. AB - In a follow-up survey of 106 settled workers' compensation cases which involved some degree of psychiatric impairment, there was found to be a high prevalence of cases in which the settlement correlated with no improvement in the patient's subjective feelings of well-being, and no improvements in employment status. There was also a large percentage of cases in which the individual continued to operate at a less adaptive level of functioning, as judged by the evaluating clinician. PMID- 6241612 TI - Follow-up studies of personal injury litigants. PMID- 6241613 TI - The role of column switching in analysing complex samples. AB - Our objective in using column switching is primarily to achieve the desired separation in the minimum analysis time. Complimentary to this aim is the need for sample and column cleanup followed by column re-equilibration. Finally, all operations should be capable of automation. Fundamental to column switching methodology is the concept of Zone cutting, where part of the chromatogram is transferred to another column. This forms the basis of sample cleanup and is a very versatile and powerful methods. Multiple zone cutting is also possible to further increase to scope of cleanup or to minimise analysis time. Zone cutting is also complimentary to the techniques of trace enrichment and recycling. Examples will be given involving the use of these techniques in the analysis of complex matrices such as urine, plant extracts, wine and serum. The latter will be used to propose a novel approach to the quantitative analysis of anti convulsants in serum using hexobarbital as internal standard. PMID- 6241615 TI - The use of [99mTc]methylene diphosphonate sequential scanning of experimental animals in evaluating the efficiency of wound healing in radical mastoidectomy. PMID- 6241614 TI - HLA specificities, lymphocyte subsets, and mitogenic response in Henoch-Schonlein purpura nephritis. AB - The present study failed to show a significant association of Henoch-Schonlein Purpura Nephritis (HSPN) with any of the HLA specificities tested. No abnormalities pertaining to in vitro lymphocyte blastogenesis to various nonspecific mitogens (PHA, PWM, ConA) were detected during the clinical remission of HSPN. During the active phase, HSPN patients developed significant lymphocytosis. The absolute numbers of OKT4+ cells (helper cells) were significantly increased but absolute numbers of OKT8+ cells (suppressor cells) were not altered. PMID- 6241616 TI - Behavioral management in dentistry. PMID- 6241617 TI - Limited licensure. PMID- 6241618 TI - [Treatment of inguinal hernia using Shouldice's technic]. AB - The very high frequency of recurrence of inguinal hernia after surgical repair during the 30s led Earl Shouldice to devote his efforts to the study of this affection. In 1945 he opened an institution for the purpose of treatment of hernia, and since then a total of 130,000 operations have been performed. Progressive advances in the techniques used have enabled the relapse rate to be reduced to less than 1%, and the procedure used at the present time is described. PMID- 6241619 TI - Enzymatic assay procedures that employ high-performance liquid chromatography: competition between phosphoribosyltransferases for a common substrate. AB - A survey of the phosphoribosyltransferase (PRTase) activities in yeast has been accomplished using reversed-phase high-performance liquid chromatographic assay procedures. The following bases were observed to be utilized during phosphoribosyl pyrophosphate (PRibPP)-dependent nucleotide syntheses: adenine, xanthine, hypoxanthine, guanine, uracil, orotate, nicotinamide, nicotinate and quinolinate. Gradient elution procedures have also been perfected that allow the separation of the two following sets of PRTase assay components: (1) adenosine monophosphate, nicotinate mononucleotide, orotate, adenosine triphosphate, nicotinate, adenosine diphosphate, inosine monophosphate and hypoxanthine, and (2) nicotinate mononucleotide, nicotinamide mononucleotide, adenosine triphosphate, nicotinate, adenosine diphosphate and nicotinamide. Separation 1 has been employed to examine the PRibPP allocation among the hypoxanthine PRTase, orotate PRTase and nicotinate PRTase catalyzed reactions, whereas separation 2 has been employed to define the role that ATP plays in the nicotinamide PRTase catalyzed reaction along with the allocation of nicotinamide between the reactions catalyzed by nicotinamide PRTase and nicotinamide deamidase. PMID- 6241620 TI - Effect of synthetic human pancreatic growth hormone-releasing factors on plasma growth hormone concentrations in lactating cows. AB - Two fragments of human pancreatic growth hormone-releasing factor, hpGRF-(1-24) NH2 and hpGRF(1-29)-NH2, were administered to lactating dairy cows in separate experiments. Each experiment involved a 4 X 4 Latin square with treatments being intravenous administration of saline (controls) or three doses of releasing factor (500, 1000, and 2000 micrograms). Administration of the 24-amino acid fragment increased plasma growth hormone concentration from baseline 3 ng/ml to peak 14 ng/ml within 10 min. Growth hormone concentrations returned to baseline by 60 min post treatment. The 29-amino acid fragment resulted in greater responses in both peak concentration (30 ng/ml) and persistency (greater than 240 min). Relationships between dose of releasing factor and response in growth hormone release (as measured by area under the response curve) were not consistent in most cows. Responses of concentrations of growth hormone in blood plasma that result from intravenous injection of up to 2000 micrograms of growth hormone-releasing factor (1-29) would not be sufficient to increase milk yield of cows. PMID- 6241621 TI - Hydrophobic interaction chromatography of Micrococcus lysodeikticus F1-ATPase. A method to detect conformational flexibility of the molecule. AB - Hydrophobic interaction chromatography of purified ATPase from Micrococcus lysodeikticus (E.C. 3.6.1.3.), a complex oligomeric protein, induces extensive conformational changes in it. In this report, we describe some physicochemical properties of the enzyme forms obtained. They can be summarized as follows. (1) The subunit stoichiometry of the enzyme is altered by the absorption and desorption process since most of the forms obtained are defective in gamma and delta subunits. An important reduction in the molar proportion of alpha subunit is also observed; (2) the fluorescence spectra of the different forms show progressive tyrosine residues which roughly correspond to the extent and strength of the interaction existing before elution of the enzyme; (3) circular dichroism measurements reveal changes of the secondary structure of the F1-ATPase undergoing an increase in alpha-helical content; (4) the ordered, active forms eluted from the hydrophobic chromatography columns are less stable than the native protein, as shown by dialysis experiments. These results while supporting the use of hydrophobic chromatography as a simplified model of membrane-membrane protein interaction, also indicate the need for caution in its application to the purification of complex membrane proteins. PMID- 6241622 TI - Left ventricular mass and function before and after antihypertensive treatment. AB - We have studied the effect of blood pressure control upon left ventricular mass and function. Twenty hypertensive patients without clinical or electrocardiographic signs of cardiac involvement were given sequentially: placebo for two weeks; captopril (250 mg/day) for eight weeks; and captopril (125 mg/day), alone or combined with chlorthalidone (25 mg/day), for eight weeks. M mode echocardiography was performed at the end of placebo period, after eight and after 16 weeks active treatment. Blood pressure was significantly reduced (p less than 0.01) by therapy, the maximum decrease being observed at the end of the study. Similarly, interventricular septal thickness, posterior wall thickness and left ventricular mass index showed a significant reduction (P less than 0.01 at the eighth and P less than 0.001 at the 16th week), while no changes were detected in left ventricular function. Furthermore, both wall stress index at end diastole and end-systolic stress were significantly lowered by treatment (at the 16th week P less than 0.01 and P less than 0.001, respectively). Baseline systolic blood pressure was inversely correlated with the ratio of the left ventricular radius to posterior wall thickness (r = -0.97, P less than 0.001) but no relation was found between post-treatment fall in either systolic or diastolic blood pressure and left ventricular mass index. After treatment more patients showed normal left ventricular wall thickness in relation to systolic blood pressure. We conclude that in uncomplicated hypertensive patients captopril, either alone or combined with chlorthalidone, can reverse left ventricular hypertrophy by decreasing both septal and posterior wall thickness.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 6241623 TI - Correlations and otherwise between blood pressure, cardiac mass and resistance vessel characteristics in hypertensive, normotensive and hypertensive/normotensive hybrid rats. AB - We have measured heart weight and properties of 150-200 microns mesenteric resistance vessels from spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), two kidney, one clip Goldblatt renal hypertensive (RHR) and outbred Wistar rats, as well as in SHR/WKY F2-hybrid rats. All rats were 14-weeks-old. In the SHRs, WKYs, RHRs and Wistars the mean blood pressures (measured intra-arterially) were, respectively: 136, 111, 164 and 100 mmHg. In the SHR/WKYs the systolic blood pressures (measured regularly over a two-week period by the tail cuff method) were normally distributed between the values obtained from control SHRs and WKYs. Relative heart weight and resistance vessel media thickness/lumen diameter ratio correlated (P less than 0.001) with blood pressure between SHRs, WKYs, RHRs and Wistars; however, no significant correlation was seen in SHR/WKYs. By contrast, the calcium sensitivity of the resistance vessel noradrenaline response did correlate (P less than 0.01) with blood pressure in the SHR/WKYs, but did not correlate between the pure strains (calcium sensitivity of the SHR and Wistar vessels was similar, but higher than that of the WKY vessels; induction of renal hypertension did not affect calcium sensitivity). The results suggest that although the cardiac enlargement and increased resistance vessel media/lumen ratio of 14-week SHRs may be advantageous for these animals, these structural abnormalities may not be primary causes of the hypertension. Furthermore, the results indicate that it is the WKYs which are abnormal in having a low calcium sensitivity of their resistance vessels, but suggest also that this reduced sensitivity may be associated with mechanisms which help to keep the WKYs normotensive. PMID- 6241625 TI - [Cardiodynamic effects of right bundle branch block III. The effects of right bundle branch block on cardiac function of the heart with right ventricular hypertrophy in the varied right ventricular afterload by pulmonary artery debanding and hypoxia]. PMID- 6241624 TI - Regression of structural cardiovascular changes by antihypertensive therapy in spontaneously hypertensive rats. AB - Trophic adrenergic influences may in part potentiate the pressure dependent development of structural cardiovascular changes in hypertension. Regression of such changes by antihypertensive treatment should therefore be most successful if adrenergic blocking drugs are used. In the present study spontaneously hypertensive rats (SHR) received either alpha-methyldopa, metoprolol, felodipine, a new vasodilating Ca2+-antagonist, or metoprolol and felodipine in combination for 10 weeks. Their left ventricles were weighed and resistance vessel design was analysed using a haemodynamic technique. Arterial pressure (MAP) was equally reduced by metoprolol and felodipine. Despite their different modes of action cardiovascular design was also equally affected. The combined regimen reduced average MAP more than either drug alone. It also caused more pronounced regression of cardiovascular structural changes. Methyldopa lowered MAP less than either metoprolol or felodipine and had only modest effects on cardiovascular design. Thus, the extent of MAP reduction, regardless of which therapeutic regimen is used to induce it, determines the extent of regression of structural cardiovascular changes during antihypertensive treatment. PMID- 6241626 TI - Neuroblastoma originating from soft tissue at the crus and its radiological feature--a case report. PMID- 6241627 TI - Dynamics of Ia-expressing cells and T lymphocytes of different subsets during experimental allergic neuritis in Lewis rats. AB - Inflammatory cells were characterized by immunohistochemistry, utilizing monoclonal antibodies against cell surface antigens in frozen sections of sciatic nerves and nerve roots of Lewis rats, sacrificed during the course of experimental allergic neuritis. Large numbers of Ia-expressing irregular macrophage-like/dendritic cells, as well as W 3/13 reactive T lymphocytes of both W 3/25 reactive helper and ox8 reactive suppressor/cytotoxic phenotypes were seen within afflicted peripheral nervous tissue at the start of clinical symptoms and at the height of the disease. T lymphocytes of both helper and suppressor/cytotoxic phenotypes decreased concomitant with clinical recovery. During this period demyelination was still extensive and Ia-expressing macrophage like/dendritic cells were abundant. PMID- 6241628 TI - The anatomy and fibre type composition of the human adductor pollicis in relation to its contractile properties. AB - We have examined the anatomy and fibre type composition of the human adductor pollicis in muscles taken post mortem. Histochemical staining of muscle fibres showed that type I fibres predominated in all cases with a mean occurrence of 80%. This composition is similar to that of the soleus muscle and unlike that of the quadriceps which has approximately equal proportions of the two fibre types. Comparing the contractile characteristics, however, the adductor pollicis has similar properties to the quadriceps and both are quite distinct from those of the slowly contracting soleus muscle. The lack of correlation between fibre composition, as revealed by histochemical staining, and contractile properties in these muscles must mean that fibres of the same type from different muscles do not necessarily have the same contractile speed. The results also suggest that the type I fibres of the human adductor pollicis are faster than those of both the soleus and quadriceps muscles. PMID- 6241629 TI - Observations on the innervation of human extraocular muscles. AB - The innervation of human extraocular muscles (EOM) was studied using a comprehensive histological and histochemical approach. In contrast to previous concepts, we have demonstrated that the coarse felderstrucktur muscle fibers are singly innervated by en plaque endings and that the fine and granular fibrillenstruktur fibers are multiply innervated by en grappe endings. Each of the fine and granular fibers is innervated by a single thin axon that travels along the fiber and sends collaterals to the en grappe endings. These findings may provide a new basis for the correlation of morphological and physiological properties of EOM. PMID- 6241631 TI - Effects of medroxyprogesterone acetate on submandibular salivary gland of female mice. PMID- 6241630 TI - Observations in studies of quantitative kinetics of tritium labelled hematoporphyrin derivatives (HpDI and HpDII) in the normal and neoplastic rat brain model. AB - Increasing interest has developed in the use of the photodynamic agent, Hematoporphyrin derivative (HpD) for photoradiation therapy (PRT) as adjunctive therapy of malignant glial tumors of the brain. HpD, injected systemically, is preferentially taken up and retained by neoplastic tissue. Early studies of such uptake have largely relied on gross fluorescence as evidence of tissue uptake. In this study HpD was labelled with a tritiated radioisotope (3H) in order to quantify tissue uptake in visceral and in normal and neoplastic brain tissues in a rat brain model. 3H-HpD was injected intravenously at a 10 mg/kg dose into 30 Sprague-Dawley rats (Group A) without tumors in order to clarify method. Separately, 3H-HpD of like dosage was injected into 20 Fischer-344 rats (Group B), 5 control and 15 with a 9L gliosarcoma implanted in the left anterior cerebral cortex. Post injection sacrifice occurred at 6, 24 and 48 hours. From the Sprague-Dawley group multiple somatic and cerebral specimens were assayed. Differential areas within the brain showed no significant difference in uptake. The tumor area, peritumoral margin, and distant uninvolved areas of the Fischer 344 9L rats were likewise assayed. Definite uptake of normal visceral and cerebral tissue occurred with a markedly higher uptake differential in tumor areas. Such differential was relatively consistent from trial to trial, but multiple separate values obtained in the respective study groups were often unreliabe in their reproducibility and at variance with previously reported tissue level studies. These findings implied an instability of 3H-HpD, subsequently confirmed chromatographically as contamination probably due to time related degradation and exchange. Therefore, 3H-HpD appears to inherently carry such a risk for contamination. The compound Photofrin II (HpDII) represents a chromatographic fraction of HpD (HpDI), currently considered its most photodynamically active and purest component. Tritiated Photofrin II was used for quantification. An assay was performed with 5 Fischer-344 9L brain tumor rats (Group C), sacrificed at 24 hours. Photofrin II provided results more reliably reproducible. Contamination, degradation, and exchange of 3H-Photofrin II did not appear to occur. Neoplastic brain levels of the Photofrin II isotope were higher than in the HpD studies, and highly fluorescent. Normal brain values were consistently minimal and without fluorescence. The differential tumor/brain ratio in Photofrin II was consequently much higher. The isolated active substrate of HpDI and HpDII (Photofrin II) appears to be the compound DiHematoporphyrin Ether (DHE).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 6241632 TI - Dynamic radionuclide study in Paget's disease before and after (Asu1,7) E calcitonin treatment. PMID- 6241634 TI - Measurement of cardiac output by the thermodilution method in conscious spontaneously hypertensive rats. AB - The usefulness of the thermodilution method for measuring cardiac output (CO) was evaluated in awake rats by comparison with electromagnetic flowmetry. CO was measured in 3- and 6-month-old conscious spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). The correlation co-efficient between CO obtained by the two methods was 0.66 (p less than 0.01). Although CO values obtained by the thermodilution technique tended to be overestimated in comparison with those determined by electromagnetic flowmetry, this method was shown to be useful for measuring CO in unanesthetized rats because of its technical simplicity. Left ventricular mass (LVM) and the ratio of CO to LVM were significantly greater in SHR than in WKY at both ages and CO/LVM increased with increasing age in SHR. The ratio of heart work (HW) to body weight (HW/BW) was increased only in 3-month-old SHR compared with WKY and there was no difference in HW/LVM in 3- and 6-month-old SHR compared with age-matched WKY. The present results suggest that the development of cardiac hypertrophy in SHR is an adaptation to the increased HW due to high afterload. PMID- 6241633 TI - [Endoluminal angioplasty for atheromatous stenoses of supra-aortic trunks. The brachiocephalic arterial trunk, subclavian arteries]. AB - The authors are reporting their experience about percutaneous transluminal angioplasty in atheromatous stenosis of proximal supra-aortic arteries. In this series of 12 patients, with an 6 months follow-up, vertigo was the main clinical symptom (6 cases), and it must be pointed out that 5 of these 6 patients also underwent a proximal angioplasty of one or the two of their vertebral arteries at the same time. Two subclavian steal syndromes, one arterial insufficiency of an upper limb, one transient cerebral ischaemia, and two asymptomatic cases were also treated by the same procedure. For diagnosis as well as for follow-up, the authors are emphasizing the value of hemodynamic results of Doppler recording. As for the technics itself, it mainly derives from the PTA of the lower limbs arteries. The results in this series appear to be good from an hemodynamic point of view, with neither morbidity, nor mortality. PMID- 6241635 TI - Dilated cardiomyopathy. An echocardiographic follow-up of 50 patients. AB - To evaluate the significance of left ventricular (LV) hypertrophy in dilated cardiomyopathy (DCM), 50 patients seen between 1976 and 1983 were studied echocardiographically. Patients were classified into 4 groups according to the degree of LV dilatation and LV hypertrophy. Group I consisted of 17 patients who had mild to moderate LV dilatation without LV hypertrophy (LV end-systolic dimension: Ds less than 60 mm, LV wall thickness at end-systole: WTs less than 15 mm). Group II consisted of 12 patients who had mild to moderate LV dilatation with LV hypertrophy (Ds less than 60 mm, WTs greater than or equal to 15 mm). Group III consisted of 8 patients who had marked LV dilatation with LV hypertrophy (Ds greater than or equal to 60 mm, WTs greater than or equal to 15 mm). Group IV consisted of 13 patients who had marked LV dilatation without LV hypertrophy (Ds greater than or equal to 60 mm, WTs less than 15 mm). Twenty patients had LV hypertrophy and 30 patients were without LV hypertrophy at the beginning of this study. New York Heart Association functional classes, cardiothoracic ratio and ECG findings during the first study did not show statistically significant difference among 4 groups. During a follow-up period averaging 2.7 years, 8 patients died of congestive heart failure (CHF), including 5 of Group IV patients and 3 of Group I patients who had progressive LV dilatation. Three patients without signs of CHF expired suddenly; they were in Groups I, II and III during the initial study. Ambulatory ECG studies showed complex ventricular arrhythmias in all 32 patients studied. In conclusion, LV wall hypertrophy in DCM may be an important factor to predict their prognosis regarding CHF death. Sudden and unexpected death could occur in any patient with DCM and intensive antiarrhythmic therapy is important. PMID- 6241637 TI - [Indication for angiography of the coronary and major vessels for the diagnosis of cardiovascular diseases. b. The present status of medical imaging technology- NMR]. PMID- 6241636 TI - Echocardiographic picture in diabetes mellitus. AB - The results of echocardiographic examination of 23 diabetics are presented. Significantly increased left ventricular posterior wall thickness and mass and elevated ratio of wall thickness to chamber radius were found in the group of diabetic patients without coronary artery disease and hypertension. The interventricular septum thickness was significantly increased only in the diabetics with hypertension. The possible causes of these findings may be the presence of microangiopathy at the periphery of the coronary circulation or the presence of PAS-positive substances with resulting interstitial fibrosis. PMID- 6241638 TI - [Blood flow measurement: a. Laser Doppler measurements of the blood flow]. PMID- 6241639 TI - [Blood flow measurement: b. Pulsed ultrasonic doppler blood flow measurement]. PMID- 6241640 TI - [Clinical significance of myocardial biopsy]. PMID- 6241642 TI - [Concepts of occupational diseases]. PMID- 6241641 TI - [Clinical utility of pulsed Doppler flowmetry in patients with liver cirrhosis]. PMID- 6241643 TI - [Effects of nifedipine on left ventricular systolic and diastolic functions in left ventricular hypertrophy]. PMID- 6241644 TI - [Four cases of diffuse bone metastasis with increased uptake in 99mTc-MDP bone scintigraphy]. PMID- 6241645 TI - [Binding of 67Ga to heparan sulfate and its sulfate contents]. PMID- 6241646 TI - Superoxide dismutase activity in diabetic rat retina. AB - We investigated the changes in superoxide dismutase activity in the retina, cornea, lens, blood, liver and kidney of streptozotocin-induced diabetic rats. Superoxide dismutase activity decreased in the retina; however, no changes were found in the cornea, lens, blood, liver and kidney. Electrophoretic studies showed no qualitative alteration of the enzyme protein in the diabetic rat retina. The present results show that superoxide dismutase activity decreased in the diabetic rat retina, and that superoxide reacted with unsaturated fatty acids of the retinal cells resulting in an increase of lipid peroxide contents. Superoxide dismutase may play a regulatory role in diabetic retinopathy. PMID- 6241647 TI - [Contact-sensitivity to p-tert-butylphenol formol (PTBP resin)]. AB - A revision of the sensitivities produced by PTBP resin is made, taking into account professional and consumers points of view. Fifteen cases of sensitivity to the resin are reported. PMID- 6241648 TI - Antibacterial efficacy of norfloxacin, trimethoprim-sulfamethoxazole, and gentamicin in experimentally-infected normal and streptozotocin-induced diabetic mice. AB - Systemic bacterial infections due to Escherichia coli MB 2884, Proteus mirabilis MB 3125 and Klebsiella pneumoniae MB 4005 were well controlled by treatment with norfloxacin both in normal and streptozotocin-induced diabetic mice. similar observations were made when trimethoprim-sulfamethoxazole was used against susceptible pathogens. Systemic infection due to Pseudomonas aeruginosa MB 4700 was well controlled by norfloxacin and gentamicin in normal mice; this infection was more refractory to treatment by both drugs in diabetic animals. These observations suggest that norfloxacin may be an effective drug in the treatment of bacterial infections which may occur under diabetic conditions, and further investigation is warranted. PMID- 6241649 TI - In vitro effect of pH and glucose concentration on the antibacterial activity of norfloxacin in urine. AB - The in vitro effect of pH and glucose concentration on the antibacterial activity of norfloxacin in urine was studied. Norfloxacin effectively inhibited the growth of four gram-negative pathogens in urine in vitro at pH values of 6.0, 7.0, and 8.0. The antibacterial activity of norfloxacin in urine was reduced severalfold at pH 6, but minimum inhibitory concentrations (MICs) at this pH remained clinically significant. Glucose at concentrations of 200 mg/dl and 400 mg/dl (simulating glucosuria of diabetes) did not significantly affect the antibacterial activity of norfloxacin when tested against clinical isolates of Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, or Pseudomonas aeruginosa. Norfloxacin appears to be a highly effective antibiotic in vitro under conditions which simulate normal and diabetic states. PMID- 6241650 TI - Physio-anatomical changes in cardiac hypertrophy. PMID- 6241651 TI - [Epizootiology and natural foci of zoonotic cutaneous leishmaniasis at the Tedzhen Oasis]. PMID- 6241652 TI - [Effectiveness of ammonia in the disinfection of biological wastes in foci of ascariasis]. PMID- 6241653 TI - [Role of the rhizosphere of plants in the self-purification of the soil in irrigated agricultural fields of helminth eggs]. PMID- 6241654 TI - [50 years' work of the Rostov Research Institute of Medical Parasitology of the Ministry of Public Health of the RSFSR]. PMID- 6241655 TI - [Sensitivity of sandflies (Diptera, Psychodidae, Phlebotominae) to DDT in a focus of visceral leishmaniasis in the Azerbaijan SSR]. PMID- 6241656 TI - [Effectiveness of examining young children for helminthiases]. PMID- 6241657 TI - [General and immunologic prevention of hepatitis B with special reference to the problem of dentists]. PMID- 6241658 TI - Neurotoxic effects of copper: inhibition of glycolysis and glycolytic enzymes. AB - The effects of Cu2+ on glycolysis and several glycolytic enzymes were studied in rat brain extracts in vitro. At concentrations reportedly found in Wilson's disease, Cu2+ significantly inhibited lactate production from glucose or glucose 6-phosphate in rat brain postnuclear supernatant with an IC50 of about 3 microM. Cu2+ also inhibited several glycolytic enzymes. Amongst the latter, Cu2+ was most effective in inhibiting hexokinase (IC50 for Cu2+ = 7 microM), moderately effective in inhibiting pyruvate kinase (IC50 for Cu2+ = 56 microM), but least effective in inhibiting lactate dehydrogenase (IC50 for Cu2+ = 300 microM). These results suggest that inhibition of brain glycolysis may have pathophysiological importance in copper poisoning and in Wilson's disease. PMID- 6241659 TI - [Development of ventricular arrhythmia in myocardial infarct as a function of ventricular kinetics. Study using echocardiography and dynamic electrocardiography]. PMID- 6241660 TI - [Evaluation of capillary flowmeters for the intravenous administration of fluids]. PMID- 6241661 TI - Alternative tracers to 18F for estimating bone blood flow. PMID- 6241662 TI - False positive bone scan due to rib fractures following cardiac resuscitation. PMID- 6241663 TI - New vistas on bone scintigraphy. PMID- 6241664 TI - Radionuclide bone scanning in the diagnosis and management of condylar hyperplasia. AB - Four patients with maxillo-mandibular facial dysharmony and four controls were evaluated by 99Tcm-MDP (methyl diphosphonate) scintiscanning. The scintiscans in all patients with dysharmony showed positive uptake of the tracer indicating the increased degree of activity in the condylar region of the mandible. The significance of this is discussed. PMID- 6241665 TI - Comparison of 99Tcm-MDP static and dynamic methods of obstructive nephropathy detection using transit times analysis as a reference: a pilot study. PMID- 6241666 TI - [Eye injuries in the Mordovian ASSR in 1977-1981]. PMID- 6241667 TI - [Dislocation of the lacrimal point]. PMID- 6241668 TI - [AIDS patients--a hazard in the environment?]. PMID- 6241669 TI - [Treatment of patients at risk in the dental office: diabetes mellitus, hyperthyroidism]. PMID- 6241670 TI - [Scintigraphy with 99mTc-methylene diphosphonate for the detection and localization of rhabdomyolysis]. AB - In 24 patients with biochemically proven rhabdomyolysis 34 scans with 99mTc-MDP were performed to detect regional as well as generalized myolysis. When performing the scan within 10 days after the maximum of myolysis, scintigraphic detection was possible in 95% of the patients, but after 20 days in none. Regional tracer accumulation in muscles was more frequent (89%) than generalized diffuse accumulation (31%). Predominantly muscles of the thigh, the buttocks and the upper arm were involved. Diffuse tracer accumulation in both kidneys occurred in 75% of patients with significant renal dysfunction. The results show that in addition to regional muscle damage generalized myolysis may be detected by scintigraphy with 99mTc-MDP. In cases of regional muscle damage scintigraphy proved to be more sensitive than clinical signs. PMID- 6241672 TI - Characterization and localization of atriopeptin in rat atrium. AB - An antiserum specific for atriopeptin was used to characterize and localize atriopeptin-like immunoreactive material in rat atrium by radioimmunoassay and immunohistochemical techniques. The antiserum recognizes atriopeptin I, atriopeptin III, and alpha-human atrial natriuretic polypeptide, but does not recognize met-enkephalin, cholecystokinin, dynorphin A, bradykinin, substance P, or beta-endorphin. A high content of atriopeptin was found in crude extracts of rat atria, as compared to ventricles, and the atriopeptin-like immunoreactive material was found to be located exclusively in granules within atrial cardiocytes. Fractionation of the immunoreactive material by gel filtration and reverse-phase HPLC revealed the presence of multiple atriopeptins. PMID- 6241671 TI - Atrial natriuretic factor (ANF) binding sites in brain and related structures. AB - Visualization of [125I]ANF binding sites in rat brain by an autoradiographic technique demonstrated that these sites are highly localized in areas such as the olfactory bulb, subfornical organ, area postrema and nucleus tractus solitarius. This distribution suggests that certain cardiovascular effects of ANF could be centrally mediated and that the existence of brain ANF-related peptides should be considered. Finally, moderate densities of [125I]ANF binding sites are found in the rat and guinea pig eye while low densities are seen in pituitary and pineal gland. PMID- 6241673 TI - [Percutaneous angioplasty of the renal artery]. PMID- 6241674 TI - Fluorescence of HpD for tumor detection and dosimetry in photoradiation therapy. PMID- 6241675 TI - Photofrin II levels by in vivo fluorescence photometry. PMID- 6241676 TI - HpD photodetection of bladder carcinoma. PMID- 6241677 TI - Picosecond fluorescence of hematoporphyrin derivative, its components and related porphyrins. PMID- 6241678 TI - A new diagnostic system for malignant tumors using hematoporphyrin derivative, laser photoradiation and a spectroscope. PMID- 6241679 TI - A trial manufacture of a motor-driven laser light scattering optic for whole bladder wall irradiation. AB - The detection of CIS of the bladder by fluorescence endoscopy with hematoporphyrin derivative (HpD) and argon ion laser was performed using a video monitoring system coupling with an image intensifier; however, it was difficult because of the reflecting light of the excitation light. Whole bladder wall photoradiation therapy was carried out in 3 patients with multicentric CIS of the bladder, using argon-dye laser light (630 +/- 1.6 nm) of 5 to 25 J/cm2. The anticancer effect of this therapy was followed by urinary cytology and clusters of vacuolated cancer cells were observed for 2 days after the therapy. PMID- 6241680 TI - Integral dye-laser irradiation of photosensitized bladder tumors with the aid of a light-scattering medium. PMID- 6241681 TI - The analysis and some chemistry of haematoporphyrin derivative. PMID- 6241682 TI - The structure of the active component of hematoporphyrin derivative. PMID- 6241683 TI - Chemical studies with hematoporphyrin derivative in bladder cell lines. PMID- 6241684 TI - Photosensitizer-protein conjugates: potential use as photoimmunotherapeutic agents. PMID- 6241685 TI - Photodynamic inactivation of cultured bladder tumor cells: a preliminary study of the effects of porphyrin aggregation. AB - This study was designed to determine the influence, if any, of intracellular porphyrin aggregation upon in vitro photosensitivity. HpD uptake conditions were manipulated in such a way as to yield three experimental groups, each containing equal levels of cellular porphyrins but having different porphyrin aggregation status. Aggregation status was determined through comparison of the spectral properties of intact cells. Subsequent exposure to red light resulted in a family of survival curves which generally corresponded to cellular HpD fluorescence yields and optical densities (indicators of aggregation status). These data suggest that porphyrin aggregation within the cell may be partially responsible for the observed differential photosensitivity following various uptake conditions. PMID- 6241686 TI - Multicellular spheroids as an in vitro model system for photoradiation therapy in the presence of Hpd. PMID- 6241687 TI - Membrane photosensitization by hematoporphyrin and hematoporphyrin derivative. AB - HPD-A, the putative active biologic component of HPD, photosensitized lysis of large phosphatidylcholine liposomes and lipid peroxidation in small liposomes with oxygen enhancement ratios from 4 to 5. Unambiguous proof was obtained that this damage was mediated by singlet oxygen. Spectral data indicates that HPD-A localizes in a heterogeneous environment in the large liposomes and within the membrane bilayer of the small liposomes. The latter was accompanied by a shift of the Soret band from 364 nm to 398 nm and a 2-3 fold increase of the fluorescence. The presence of human serum albumin protected the large liposomes from photosensitized damage by HPD-A and inhibited the diffusion of HPD-A into the small liposomes. In connection with photoradiation therapy, these findings suggest that aggregated HPD-A and the more fluorescent, disaggregated HPD-A may act as photodynamic sensitizers after localization, and that binding of HPD-A to serum protein protects the aggregated form and inhibits photodynamic damage to membranes. However, protein photooxidation is feasible in the protein-bound state. PMID- 6241688 TI - Chemical and biochemical determinants of porphyrin localization. PMID- 6241689 TI - Porphyrin-sensitized photoinactivation of cells in vitro. PMID- 6241690 TI - Cellular binding of hematoporphyrin derivative (HpD) in human bladder cancer cell line: KK-47. AB - In vitro cellular uptake or binding of hematoporphyrin derivative (HpD) was investigated by comparing the optical properties; absorption spectra, fluorescence spectra, fluorescence lifetime and fluorescence polarization, of HpD in KK-47 cells derived from a human bladder carcinoma, organic and micellar solutions. In addition, the relationship between the mode of cellular HpD uptake and photodynamic cellular inactivation by argon-dye laser was studied using a clonogenic assay system. HpD molecules may weakly bind to the cell membrane within approximately 2 hrs after incubation in HpD-containing medium, and then major HpD molecules may slowly be distributed throughout the cytoplasm as a dimer form for 4 hrs after incubation in HpD-free medium. The intracellular binding loci were found to be the mitochondria and nuclear membrane by subcellular fractionation and fluorescence microscopic studies. The loci may be relatively hydrophilic on the basis of the polarity-dependence data on the fluorescence polarization. An exponential cellular photoinactivation curve was observed in relation to increasing concentrations of HpD and to intracellular strong-binding of dimeric HpD. PMID- 6241691 TI - Examination of action spectrum, dose rate and mutagenic properties of hematoporphyrin derivative photoradiation therapy. PMID- 6241692 TI - Parameters of hematoporphyrin derivative tumor cell killing efficiency: decomposition of hematoporphyrin derivative at high power densities. AB - Hematoporphyrin derivative (HpD) tumor cell killing efficiency has been evaluated as a function of power density, optical spectrum, HpD concentration, and HpD preparation using trypan blue exclusion assay. Cell survival curves for Mayo Clinic HpD and for Photofrin were equivalent at all concentrations and power densities for both violet and red light. Survival curves for red light demonstrated a two-fold increased cellular killing efficiency at higher densities (160 mW/cm2). However, for violet light an irreversible and marked decrease in cellular killing efficiency was found as the power density was increased. This phenomena of decreased cellular killing efficiency of violet light at high power densities is consistent with a process of photo-decomposition of HpD and is most pronounced at low concentrations (less than 25 micrograms/ml). PMID- 6241693 TI - Uptake and localization of HPD and "active fraction" in tissue culture and in serially biopsied human tumors. PMID- 6241694 TI - Fluorescing cells in sputum after parenteral HpD. AB - Cells exfoliated into sputum were examined for fluorescence after the intravenous injection of HpD. Malignant and non-malignant cells were seen to fluoresce up to 9 days post injection of HpD. Not all exfoliated squamous cell cancer cells or non-malignant cells fluoresced. Implications are discussed relative to imaging diagnostic fluorescence bronchoscopy and photoradiation therapy of obstructing endobronchial cancers and bronchial carcinoma in situ. PMID- 6241695 TI - Hematoporphyrin derivative and pulse laser photoradiation. PMID- 6241696 TI - Tissue distribution of 3H-hematoporphyrin derivative and its main components, 67Ga and 131I-albumin in mice bearing Lewis lung carcinoma. PMID- 6241697 TI - Effects of hematoporphyrin (HPD) and a chemiluminescence system on the growth of transplanted tumors in C3H/HeJ mice. AB - Photoradiation therapy is emerging as a promising technique for combating cancer. Fundamentally, this approach consists of two steps: hematoporphyrin derivative (HPD) is used to selectively sensitize cancer cells to visible light; after an appropriate time interval, light is introduced into the tumor via a laser-fiber optic system to trigger the cytotoxic action of HPD. The present investigation was initiated to determine the therapeutic potential of HPD in combination with a chemiluminescent activator in treating mice which had been transplanted with tumors. PMID- 6241698 TI - Dose effect relationships in a mouse mammary tumor. PMID- 6241699 TI - Documentation of radioactive contaminants in tritium labeled hematoporphyrin derivative. PMID- 6241700 TI - Studies on the mechanism of tumor destruction by photoradiation therapy. PMID- 6241701 TI - Phototoxicity of brain tissue in hematoporphyrin derivative treated mice. AB - Photoradiation therapy conditions which have been used to treat subcutaneous and breast tumors are lethal when applied to the head of mice. Treatment of control mice with laser light at 631 nm over an energy density range of 0-90j/cm2 had no measurable effect but mice photosensitized with 5 mg HPD/kg 72 hrs prior to laser treatment showed a threshold for brain damage at 56j/cm2, above which the mice developed cerebral edema and died. Laser treatment caused the same rate and magnitude of temperature rise in both control and HPD-photosensitized mice. Moreover, studies using mice whose brain temperature was kept below 37 degrees C during laser treatment showed a greater phototoxicity than mice without temperature regulation. Therefore, temperature rise in cerebral tissue was not associated with phototoxicity in the brain. In contrast the oxygen consumption rate in a brain cell suspension from an HPD-treated mouse was only 54% of that from a control mouse following treatment with laser light. This observation, when taken with supporting data from other investigations, suggests that one mechanism for the phototoxic response in brain tissue is oxygen deprivation resulting from mitochondrial damage. PMID- 6241702 TI - 64Cu labelling of hematoporphyrin derivative for non-invasive in-vivo measurements of tumour uptake. PMID- 6241703 TI - Destructive effect of photoradiation on the microcirculation of a rat mammary tumor growing in "sandwich" observation chambers. PMID- 6241704 TI - Photoradiation therapy of Lewis lung tumors in mice with low optical dose rat and high HpD-dose. AB - Lewis Lung carcinomas in B6D2 mice have been treated by photoradiation therapy (PRT). All irradiations were performed at 630 nm. The optical power levels were typically varied from 45-100 mW with a radiation duration of 60 min. This gave an optical energy of 160-360 J delivered through a centrally inserted optical fiber into the tumor during treatment. The optical power density and the temperature were monitored during exposure. After treatment the animals were observed for at least two days before sacrifice. Biopsies have been taken for the histological follow-up. The experimental series were composed of non-treated controls and treated cases with variations in the chemical and optical dose scheme. Only the high (50 mg/kg) Hematoporphyrin derivative (HpD)-dose gave curative response from the tumors. The low dose (5 mg/kg) gave no significantly different response from the control case by visual observation; however, histologically there was some difference. PMID- 6241705 TI - Porphyrin:protoporphyrin:plasma protein interaction--the metabolic basis for the tumor localization of hematoporphyrin derivative--a preliminary report. PMID- 6241707 TI - Optimal photodynamic band of red light in hematoporphyrin derivative (HPD) photoradiation therapy of cancer. PMID- 6241706 TI - A comparative study of 28 porphyrins and their abilities to localize in mammary mouse carcinoma: uroporphyrin I superior to hematoporphyrin derivative. AB - Hematoporphyrin derivative (HPD), a complex mixture of porphyrins has been used clinically as a tumor localizer both for diagnostic and therapeutic purposes. Relative lack of tumor specific uptake limits widespread clinical application. In an attempt to circumvent this problem, we studied 28 porphyrins with widely differing properties using a transplantable KHJJ mammary carcinoma in the mouse (Balb C) as a tumor model. Twenty hours after porphyrin (P) administration, the tumor, skin and gastrointestinal tract were excised and the latter lavaged with physiologic saline. Tissue porphyrin content was assessed visually by red U.V. fluorescence, and by quantitative fluorometric extraction, and photodynamic activity was evaluated in vivo using a tuneable dye laser emitting red light (615 640 nm). (1) Of the five porphyrins which were taken up by tumor tissue, i.e. HPD (photofrin), photofrin II, meso-tetra (4-carboxyphenyl) porphine (TCPP), tetra sodium-meso-tetra (4-sulfonatophenyl) porphine (TPSS), and uroporphyrin I (UROP I), skin and intestinal fluorescence also was marked with the notable exception of those mice receiving UROP I. (2) UROP I clearly was superior to HPD in this study in that the tumor to skin porphyrin content ratio was more than seven times greater than the ratio observed with both HPD and photofrin II, (3) As no measureable UROP was present in the gut, the tumor:intestinal P ratio under conditions of assay was for practical purposes infinity. (4) Photodynamic necrosis in the tumors of UROP I treated animals was similar to that seen following treatment with HPD. We conclude that UROP I appears the most specific tumor localizing porphyrin yet studied. This specificity suggests major potential clinical application both as a diagnostic marker for early mucosal cancer, and in photoradiation therapy. Moreover, the prolonged photocutaneous side effects as seen with HPD are unlikely. PMID- 6241708 TI - Multidisciplinary approach to phototherapy of human cancers. PMID- 6241709 TI - Phototherapy in malignant brain tumors. PMID- 6241710 TI - HpD photodynamic therapy for obstructing lung cancer. AB - Twenty-two patients with endobronchial cancer of the lungs have been treated with photoradiation therapy (PRT) employing a set protocol of 3.0 mg/kg hematoporphyrin derivative (HpD) administered intravenously 72 hours prior to red light (630 nm) illumination via a bronchoscope. Twenty patients showed a complete response. Of these, nineteen had large obstructing endobronchial tumors; one had a small mucosal lesion. Only one patient with an obstructing tumor showed a partial response. The one showing no response had an endobronchial mass that consisted of fibrous tissue, not tumor, as shown on three separate bronchoscopic biopsies. PMID- 6241711 TI - Indications of photoradiation therapy in early stage lung cancer on the basis of post-PRT histologic findings. PMID- 6241712 TI - Photoradiation therapy in the treatment of advanced carcinoma of the trachea and bronchus. PMID- 6241713 TI - Gynecologic uses of photoradiation therapy. PMID- 6241714 TI - Photoradiation of choroidal malignant melanoma. PMID- 6241715 TI - Photoradiation therapy of bladder tumors. AB - Photoradiation therapy (PRT), in which hematoporphyrin derivative (HpD) is activated by an argon-dye laser, was performed on 46 superficial bladder tumors in 9 patients. It was suggested there is little or no thermal cell killing effect of laser irradiation from a study of the heating effect of the beam intensity. A fluorospectrophotometric study of biopsies from tumors and normal mucosa revealed preferential HpD localization in malignant tissues. In tumors less than 1 cm in diameter treated with 150 mwatts per cm2 for 5 minutes there were 2 with complete remission (CR) and 5 with no change (NC), whereas with 200 mwatts per cm2 or more for the same time there were 15 CR and 5 with partial remission (PR). Concerning the accumulated energy intensity of light, in tumors 1 cm in size or less, treatment with 100-250 joules per cm2 obtained CR in 5 of 6 tumors. From these results, it was suggested that the light intensity should be 300 mwatts per cm2 for 5-10 minutes or more and the total light dose should be 100 joules per cm2 or more in tumors up to 2 cm in size. There was no CR in tumors more than 2 cm in size. No early side effects were seen from administration of HpD. Sensitivity to sunlight was seen in 4 cases. PMID- 6241716 TI - The use of hematoporphyrin derivative (HpD) in the localization and treatment of transitional cell carcinoma (TCC) of the bladder. PMID- 6241717 TI - Photoradiation of malignant tumors presensitized with hematoporphyrin derivative. PMID- 6241718 TI - A teaching program for oncology patients considering and receiving hematoporphyrin sensitization and photoradiation. PMID- 6241719 TI - Imaging fluorescence bronchoscopy for localizing early bronchial cancer and carcinoma in situ. AB - A system of imaging fluorescence bronchoscopy instrumentation and methods has been devised that has succeeded in localizing very small (1 X 2 mm) areas of bronchial mucosal cancer, in individuals with radiologically occult lung cancer (positive sputum cytology for malignant cells and a negative chest X-ray). These areas were located solely by their fluorescence, and were visibly normal on white light examination. The detection of lung cancer in individuals with radiologically occult lung cancer depends upon adequate methods of sputum collection and processing. Proving that fluorescing areas show "true positive" fluorescence depends upon accurate brush and forceps biopsies, providing adequate cytological and biopsy material. The entire system of the diagnosis and localization of early or pre-invasive lung cancer (while still confined to a bronchus) rests on skilled cytopathology methods and interpretation, not only skilled fluorescence bronchoscopic examination and adequate instrumentation. PMID- 6241721 TI - Cisplatin-induced tubular injury studied by water-soluble synthetic polymers. AB - Accumulation of a synthetic water-soluble polymer, poly-alpha, beta-[N(2 hydroxyethyl)-D,L-aspartamide-co-N(4-hydroxyphenethyl )- D,L-aspartamide] in the cells of kidney proximal tubules was used as an indicator for the functional localization of Cisplatin (CDDP) induced tubular injury in rats. Tubular accumulation of polymer was examined using 131I and fluorescence labelling for quantitative as well as morphological evaluation. It was found that reabsorption of the polymer, in which mainly the epithelium of proximal convolutions is involved, remains unaffected upon CDDP treatment in the course of one to six days after the drug administration. This finding supports on the functional level the morphological localization of CDDP injury into the straight segment of the proximal tubule. PMID- 6241720 TI - [Comparative studies on the bioavailability of various drug forms of phenylbutazone and clofezone (Perclusone)]. AB - The bioavailability (BA) of phenylbutazone and clofezone preparations had been determined in patients suffering from rheumatic diseases. Clofezone is a compound preparation of phenylbutazone and clofexamide, with which the phenylbutazone portion amounts to 49%. In spite of an equivalent dosage (0.4 g phenylbutazone or 0.8 g clofezone, resp.) significant differences in the phenylbutazone-serum level profile had partly been stated after the application of different kinds of the preparation of both the drugs. The oral administrations (phenylbutazone dragees, Perclusone capsules) resulted in a prompt resorption; the plateau values of the phenylbutazone concentration in serum had already been completed after 2-3 h. The resorption from suppositories was decreased. The serum level maximum with phenylbutazone suppositories occurred after 6 h, with Perclusone suppositories after 24 h only. Compared to the phenylbutazone i.v. injection, the phenylbutazone dragees proved a complete substance uptake into the systemic circulation, whereas a relative BA of 65% has been determined for Perclusone capsules. The BA of the phenylbutazone suppositories amounted to 67%, those of the Perclusone suppositories to 41%. PMID- 6241722 TI - The ultrastructure of mammary explants from virgin ovariectomized goats during hormone-induced lactogenesis. AB - The effect of insulin (I), cortisol (F) and prolactin (P) on the ultrastructural morphology of epithelial cells of cultured mammary explants from virgin ovariectomized (OV-X) goats were studied. The epithelial cells showed little structural organization and were devoid of fat droplets and secretory protein granules at zero time of culture. The cytoplasm contained few profiles of smooth and rough endoplasmic reticulum and the Golgi apparatus was rudimentary. After being cultured in Waymouth's medium without added hormones the epithelial cells were indistinguishable from epithelial cells of uncultured explants. The addition of I induced changes mainly in the appearance of nucleoli. The nucleoli were enlarged and fibrillogranular areas with light spaces were observed. The most obvious cytological changes of epithelial cells of explants cultured in the presence of I and F are translocation of the nucleus into the basal cytoplasm, increase of rough endoplasmic reticulum, an increase in the size of the Golgi apparatus, presence of one or two lipid droplets and in some cells vacuoles with protein granules were present. Mitochondria were more abundant. The epithelial cells of explants cultured in the presence of I, F and P were characterized by the polarization of organelles within the cytoplasm and by the formation and release of protein granules and small and large fat droplets. The cell nucleus was in the basal cytoplasm, the Golgi apparatus was supranuclear. The rough endoplasmic reticulum was extensively developed and formed large sacs. Golgi vacuoles contained protein granules.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 6241723 TI - Effect of triiodothyronine or etiroxate on DNA synthesis in intact and regenerating liver. AB - An increase in liver DNA synthesis (p less than 0.01) was found in rats with an intact liver 24 h after the administration of a single dose of triiodothyronine (200 micrograms/kg i.g.) Statistically significant stimulation of DNA synthesis was also found in rats given triiodothyronine (p less than 0.01) or etiroxate (p less than 0.05) for 3 days at 24-hour intervals. When a single dose of triiodothyronine was administered immediately after partial hepatectomy (65-70% resection of the liver), increased stimulation of DNA synthesis (p less than 0.01) was found 24 h after the operation. Etiroxate partly inhibited DNA synthesis (p less than 0.05). In rats given triiodothyronine at 24-h intervals, starting at the time of partial hepatectomy, DNA synthesis 72 h after the operation was double the value in the control group. Marked stimulation of DNA synthesis by triiodothyronine (p less than 0.01) and an increase in the total DNA content of the liver (p less than 0.05) were likewise found 48 h after partial hepatectomy if the hormone was administered once, 24 h after the operation. The increase in the two indicators after the administration of etiroxate was not statistically significant. PMID- 6241724 TI - Nutritional dependence of the incidence of selenite-induced cataracts in rats. AB - The protective effect of premature weaning on the incidence of selenite-induced cataracts in young rats can be abolished by the timely administration of the main components of nourishment, including water. The results suggest that water which is a common factor of all supplemented nutrients could play an important role in the development of selenium cataract. PMID- 6241725 TI - Effect of food synchronization on the circadian rhythm of bone marrow and thymus lipids in rats. AB - Young male Wistar rats reared under standard laboratory conditions with a 12:12 h light:dark regimen were fed ad libitum or were allowed access to food for only 2 h in the first half of the light or the dark part of the day. In rats fed ad libitum, marked circadian oscillation of the bone marrow triacylglycerol and phospholipid concentration and oscillation of the same fractions in the thymus were found. The restricted feeding time raised the triacylglycerol concentration in the bone marrow, but did not noticeably affect the time course of the circadian curves. The mean lipid values in the thymus of animals with a shortened feeding time did not alter, but the acrophase of the two basic fractions shifted. PMID- 6241726 TI - Proceedings of the Czechoslovak Physiological Society. Abstracts. PMID- 6241727 TI - Serum beta-hexosaminidase and alpha-L-fucosidase in relation to glycosylated hemoglobin in juvenile "diabetes mellitus". PMID- 6241728 TI - Biology of human megakaryocytes: recent developments. PMID- 6241729 TI - An assessment of regional versus systemic thrombolytic treatment of peripheral and coronary artery thrombosis. PMID- 6241730 TI - [Bronchial cancer in anthracosilicosis and silicosis. Study of workers in coal fields in Wallonia]. AB - This study was carried out between 1973 and 1982 on the proportional mortality by lung cancer of a group of workers living either in Brussells or in Wallonia and receiving compensation for silicosis or anthrasilicosis. The majority of patients suffered from anthrasilicosis (more than 96%) and had been exposed to the risk of pneumoconiosis in one of the four coal fields in Wallonia. If, in 13,822 deaths studied the proportional mortality from lung cancer had grown by 0.56% per year reaching 3.7% in 1973 and 9.3% in 1982, it remained below that for a similar Belgian population matched for age and sex. No correlation could be found between the occurrence of this tumour and one or other radiological category as defined by the international classification of pneumoconiosis in 1980. In addition the severity of pneumoconiosis, either from a radiological or functional view, hardly had any influence on the genesis of lung cancer. Finally, the localisation of the tumour and the different histological types do not differ from that reported in the literature among the general population. On the other hand a significant rise in proportional mortality from lung cancer between 1973 and 1982 (p less than 0.001) seemed to be related to two factors, smoking habitis (89.1% of subjects dying from lung cancer were smokers at the moment of death against 68.5% of smokers among other causes of death), and above all the progressive aging of the population of pneumoconioties receiving compensation, the cross section 50-69 rose from 53.17% in 1973 to 73.8% in 1982. PMID- 6241732 TI - [Hemispheric asymmetry in mental diseases]. PMID- 6241731 TI - [Regulation of integrative recombination in bacteriophage lambda]. PMID- 6241733 TI - [Electrocardiographic aspects of acute cerebrovascular diseases]. PMID- 6241734 TI - [Risk factors for nonembolic cerebral ischemic accidents in young adults]. PMID- 6241735 TI - [Residual serum activation time in diagnosing ischemic cerebrovascular diseases]. PMID- 6241737 TI - [Information supplied by vestibular tests (spontaneous and provoked with electronystagmographic recording) in the diagnosis of otoneurological and neurological lesions]. PMID- 6241736 TI - [A combined recuperative treatment plan in multiple sclerosis]. PMID- 6241738 TI - [Clonazepam in the treatment of tardive dyskinesia]. PMID- 6241739 TI - [Cerebrovascular ischemic accidents occurring within an 8-month interval in monozygotic (univitelline) twin brothers (clinical demonstration of the biochemical and cytogenetic distinctiveness)]. PMID- 6241740 TI - [Dynamic clinico-psychological study of a factory worker group with an increased risk of developing neuroses]. PMID- 6241742 TI - [Philippe Pinel (1745-1826)]. PMID- 6241741 TI - [Onset modalities of schizophrenia in young people]. PMID- 6241743 TI - [Interleukins as modulators of the immune system]. PMID- 6241744 TI - Short-term effects of desogestrel and ethinyloestradiol on serum proteins in women. AB - The effects of the new progestagen desogestrel on the changes induced by ethinyloestradiol (EE) on the serum levels of sex hormone binding globulin (SHBG), transcortin, ceruloplasmin and haptoglobin were studied in healthy female volunteers. Desogestrel (0.125 mg or 0.250 mg) administered in combination with 0.050 mg EE was compared with 0.050 mg EE alone. After 7 and 14 days the three regimens induced similar changes in the serum levels of transcortin, ceruloplasmin and haptoglobin. Desogestrel at a dose level used in oral contraceptives did not inhibit the EE-induced increase in SHBG capacity while its influence on this parameter at twice the clinical dosage (0.250 mg) used was still minor. It can be concluded that with respect to the parameters studied desogestrel in the clinical dosage used has no detectable oestrogenic or androgenic effect. PMID- 6241746 TI - Cardiac failure without cardiomegaly. PMID- 6241745 TI - The role of alcohol abuse in working disability in patients with low back pain. AB - The prevalence of alcohol problems was investigated in 50 patients with chronic low back pain, and compared to an age, sex, civil status, and income matched control group. Alcohol abuse was significantly more frequent among the male low back patients. Within the patient group the use of analgesics and sedatives was not related to the degree of alcohol consumption. Alcohol problems were not found to influence the rehabilitation process negatively, probably because the rehabilitation programme was not directed to the back only. Such problems therefore should not discriminate against inclusion in a rehabilitation programme. PMID- 6241747 TI - The effect of acute alcohol withdrawal on the serum potassium and total body potassium in heavy drinkers. AB - In a group of 20 patients with heavy alcohol intake a relation was found between withdrawal symptoms and fall in serum potassium. Total body potassium (TBK) was measured in all subjects and was lower in the group of subjects who displayed symptoms than in the group who did not. The subgroup of the four most severe reactors had a mean TBK value significantly less than the 'non-reactor' group. The minimum serum potassium levels observed for all subjects in the four day period following alcohol withdrawal correlated with their TBK values. We suggest that the mechanism for the serum potassium fall might be overactivity of the Na-K pump caused by ethanol consumption. There was also an association between withdrawal reaction and abnormal liver function and a transient rise in serum phosphate in the more severely reacting subjects. PMID- 6241748 TI - [The mechanisms of antagonistic action of prostaglandin E1 against As2O3-induced hypothermia]. PMID- 6241749 TI - Patient evaluation of a cognitive behavioral group program for patients with chronic low back pain. AB - Traditional approaches to curing patients with chronic benign pain have had only limited success. Rehabilitation becomes therefore more important and in recent years management programs have been developed to achieve this goal. This study was based on the hypothesis that a program can be more effective with its structure according to the comments of patients with respect to the various components of the program. After testing this hypothesis we conclude that such subjective evaluation of treatment is an important factor which merits receiving more attention than previous work has suggested. PMID- 6241750 TI - Platelet aggregation, beta-thromboglobulin and platelet factor 4 in diabetes mellitus and in patients with vasculopathy. AB - We have studied 155 subjects, 48 normals, 36 diabetics without complications, 44 with complications and 27 patients with macroangiopathy. beta-Thromboglobulin (beta-TG) and platelet factor 4 (PF4) are elevated in the patients groups. There is no correlation between the plasma levels of beta-TG and the stages of either retinopathy or macroangiopathy or nephropathy. The difference is more marked between normals and diabetics with neuropathy (p = 0.026). The aggregation response to ADP and platelet activating factor (PAF) is enhanced at lower stimulator concentration. Using the beta-TG, PF4 and aggregation values the discriminant analysis allows a distinction of several subgroups especially with nephropathy and neuropathy (Table 6). PMID- 6241751 TI - Abnormal haemostasis and blood viscosity in malignant hypertension. AB - We have previously shown abnormalities of haemostasis suggestive of intravascular coagulation in patients with malignant hypertension, a condition associated with retinopathy and renal fibrin deposition. To determine whether such abnormalities are specific to malignant hypertension, we have measured several haemostatic and haemorheological variables in 18 patients with malignant hypertension (Group 1), 18 matched healthy controls (Group 2), and 18 patients with non-malignant hypertension (Group 3) matched for renal pathology, blood pressure and serum creatinine with Group 1. Both Groups 1 and 3 had increased mean levels of fibrinogen, factor VIIIc, beta-thromboglobulin, plasma viscosity and blood viscosity (corrected for haematocrit); and decreased mean levels of haematocrit, antithrombin III and platelet count. Mean levels of fast antiplasmin and alpha2 macroglobulin were elevated in Group 1 but not in Group 3. We conclude that most blood abnormalities are not specific to malignant hypertension; are also present in patients with non-malignant hypertension who have similar levels of blood pressure and renal damage; and might result from renal damage as well as promoting further renal damage by enhancing fibrin deposition. However increased levels of fibrinolytic inhibitors in malignant hypertension merit further investigation in relation to removal of renal fibrin. PMID- 6241752 TI - Agglutination of formalin-fixed, platelet-type von Willebrand's disease platelets by human von Willebrand factor. AB - The interaction of platelets and von Willebrand factor (vWF) in platelet-type von Willebrand's disease (vWD) was characterized using formalin-fixed platelets from the patients. Formalin-fixed patient platelets were agglutinated directly by human vWF in normal plasma and type IIB vWD plasma, but not in type IIA vWD plasma. In the presence of a small amount of normal vWF, ristocetin-induced agglutination of patient platelets was enhanced with low concentrations of ristocetin. Wheat germ agglutinin and EDTA inhibited vWF-induced agglutination, although EDTA had no effect on ristocetin (plus vWF)-induced agglutination. These results demonstrate that vWF-induced agglutination of platelet-type vWD platelets is independent of active platelet metabolism but requires divalent cations, and suggest that platelet membrane glycoprotein I (GPI) would be involved in this agglutination. PMID- 6241753 TI - The use of functional and quantitative assays to study glycoprotein Ib in platelets stored under various in vitro conditions. AB - There is much evidence to suggest that platelet membrane glycoprotein Ib is involved in the haemostatic function of platelets and it has been suggested that loss of this glycoprotein may occur during in vitro storage of platelet concentrates. In this study two quantitative radioimmunoassays were developed to measure the content of glycoprotein Ib in platelets stored under a range of conditions used in blood banks. One assay involved the use of iodinated Maclura pomifera lectin and the other the binding of a monoclonal antibody (AN51) specific for glycoprotein Ib. The results showed that there was no significant reduction in the glycoprotein Ib content of platelets under the storage conditions used. These results suggest that any loss of haemostatic effectiveness which occurs on in vitro storage of platelet concentrates is not attributable to a selective loss of glycoprotein Ib from the platelet surface. PMID- 6241754 TI - Exercise-induced platelet activation in myocardial infarction survivors with normal coronary arteriogram. AB - Platelet activation may participate in the pathophysiology of myocardial infarction occurring in patients with normal coronary arteriogram. We investigated this possibility in a series of 9 such patients (group A) during a standardized bicycle exercise test as myocardial infarction had occurred in all of them during or soon after strong physical exercise. Twelve patients with effort-induced angina and coronary atherosclerosis (group B) and eleven healthy subjects (group C) served as test groups. Peripheral venous blood was collected by separate venipuncture before, at peak exercise and during recovery. As a sensitive index of activation, the shape of the circulating platelets was examined with a phase contrast microscope after instantaneous fixation of the whole blood. The percentage of non strictly disc-shaped platelets with one or more thin pseudopods was determined. Simultaneously, the plasma levels of platelet factor 4 (PF4) and of beta-thromboglobulin (beta-TG) were measured. At rest, there was no significant difference in the platelet morphology nor in the plasma levels of platelet specific proteins between the three groups. During exercise, a significant change in platelet shape occurred in group A and B patients and not in the healthy subjects. This platelet activation was not related to myocardial ischemia since it occurred to a similar extent in group B patients who developed electrocardiographic changes and in group A patients who did not. There was no detectable release of platelet proteins during exercise in any group. PMID- 6241755 TI - Progressive exposure of E-neoantigen associated with degradation of crosslinked fibrin by plasmin in vitro. AB - Fragment E-neoantigen (Eneo) is a specific marker of structural and conformational changes associated with the degradation of fibrinogen and its related proteins. In this study Eneo expression was followed during the plasmin degradation of crosslinked (XL) fibrin in vitro, utilizing double antibody radioimmunoassay. Eneo was progressively exposed as degradation proceeded and its expression was associated with the liberation of high molecular weight fragments from XL-fibrin, their degradation into fragments DD and E, and the partial degradation of fragment E itself. An isolated protein fraction containing early high molecular weight fragments (MW greater than 360 000 d) and a fraction containing fragments YY and DY expressed approximately 170 times and 15 times less Eneo per protein respectively compared to the fragment E standard. XL-fibrin fragment E isolated from 1-hr plasmin digest expressed approximately 8 times less Eneo than fragment E isolated from 24-hr digest, indicating increased exposure of Eneo during fragment E degradation. Eneo expression of this terminal fragment E was comparable to fibrinogen fragment E. As expected, fragment DD had no Eneo immunoreactivity. PMID- 6241756 TI - [Contribution of echocardiography in hypertensive cardiopathies]. PMID- 6241757 TI - A noninvasive diagnostic method for aortic regurgitation by detecting carotid blood flow with bidirectional Doppler ultrasound. AB - This paper reports a safe, noninvasive and accurate method for estimating aortic regurgitation. It is possible to detect some quantitative features of the disease from the velocity information obtained from the common carotid artery with the bi directional velocimeter (model F1) developed by the authors. The diastolic murmur over the aortic region is a quantitative feature of the disease. With the theory of quantification I, both qualitative and quantitative variables were processed. A prediction formula was obtained to assess the degree of aortic regurgitation. The results of such predictions in 15 normal subjects and 25 patients are given. All the patients underwent retrograde aortography or operation to provide comparison with the ultrasonic measurements. PMID- 6241758 TI - Epidural opiates and degenerative back pain. PMID- 6241759 TI - Stress fractures in athletes. PMID- 6241760 TI - [Diagnosis of malignant lymphomas (review of the literature)]. PMID- 6241761 TI - [Use of amopen foaming tablets in treating chronic endometriosis in cows]. AB - Pharmaceutic studies were carried out with a total of 89 cows affected with chronic endometritis, following up the biopharmacokinetic and therapeutic effect of amopen foaming tablets that contained amoxicillin trihydrate at the rate of 30,000 and 45,000 IU. Andreev's catheter was used to introduce the tablets into the uterus. It was found that the use of 600,000 IU amoxicillin developed therapeutic concentrations within the uterus up to the 48 h-72nd hour. Amoxicillin persisted in the blood serum up to the sixth hour. It was not eliminated by milk. The therapeutic effect with such cows (in which the causative organisms were susceptible to amoxicillin) to which the amopen tablets were introduced into the uterus (14 t. x 630,000 IU) three to four times at 48-hour intervals was shown to be 76 per cent. The use of 5 tablets of 45,000 IU at the 24th hour after the last insemination of cows that failed to conceive, exhibiting no symptoms of inflammation, raised the conception rate by 24.1 per cent. PMID- 6241762 TI - [Problems of surgical treatment of giant postoperative ventral hernias]. PMID- 6241763 TI - [Perivesical hematoma as a rare cause of excretory anuria]. PMID- 6241764 TI - Studies on the induction of aryl hydrocarbon(benzo[a]pyrene) hydroxylase in Neurospora crassa, and its suppression by sodium selenite. AB - Six fungal species were grown in the presence of benzo[a]pyrene (BP); four showed benzo[a]pyrene hydroxylase (aryl hydrocarbon hydroxylase, AHH) activity. Penicillium sp. and Neurospora crassa metabolized BP to a limited extent. N. crassa AHH activity was induced by BP, the major product of metabolism being 3 hydroxy-BP. Both induction of AHH activity and metabolism of BP were suppressed by sodium selenite in the growth medium. Two polypeptides, unique to BP-grown cells, were revealed by two-dimensional electrophoretic separation of [35S]methionine-labelled proteins in N. crassa cell extracts. In selenium-grown cells the synthesis of BP-specific polypeptides was severely inhibited. PMID- 6241765 TI - Dependence on membrane lipids of the effect of vanadate on calcium and ATP binding to sarcoplasmic reticulum ATPase. AB - The affinity of the sarcoplasmic reticulum transport ATPase for calcium and ATP is not affected by lipid deprivation while vanadate binding is completely abolished. Lipid substitution restores vanadate binding as well as the vanadate induced disappearance of the enzyme's high affinity calcium and nucleotide binding sites. Nucleotide binding is simultaneously restored with the displacement of vanadate from the enzyme following the occupation of its low affinity calcium binding sites. PMID- 6241766 TI - Inhibitors of calmodulin-dependent phosphorylation simultaneously inhibit calcium uptake and calcium-dependent ATPase activity in skeletal muscle sarcoplasmic reticulum and transiently induce calcium release. AB - Under adequate experimental conditions calmodulin antagonists like compound 48/80 do not dissociate calcium uptake from the calcium-dependent ATP hydrolysis of skeletal muscle sarcoplasmic reticulum membranes but simultaneously inhibit both processes. Apart from the agent's pump inhibiting effect, they interact with the caffeine sensitive calcium channel in the sarcoplasmic reticulum causing a rapid transient calcium release. PMID- 6241767 TI - Immunogenicity of HBV vaccine in healthy Chinese children. AB - The immunogenic response of healthy Chinese children to three different doses of hepatitis B virus (HBV) vaccine was compared. One hundred susceptible children received two doses of 10, 20 or 40 micrograms a month apart. A month following the first dose 33% of all the children had antibodies. The response rate rose to 78% a month later and 99% four months later. Ninety percent of the 100 children still had antibody at 12 months after vaccination was initiated. The response rate, antibody levels and persistence of antibody were directly related to the dose of vaccine and inversely to the age of children. No adverse reactions were observed. PMID- 6241768 TI - Hepatitis B vaccines. PMID- 6241769 TI - Elimination of serum proteins and potential virus contaminants during hepatitis B vaccine preparation. AB - As first generation hepatitis B vaccines are derived from human plasma, detailed information is required concerning the elimination of hepatitis B virus and other potential transmissible infectious agents during vaccine preparation. To demonstrate the safety of a hepatitis B vaccine, the efficiency of each of the six main steps used in the preparation process to remove or destroy pathogens was determined for representatives of major groups of animal viruses. Infectivity of all the tested viruses was reduced 10(5)-fold to a factor of 10(9)-fold by the first and last steps, namely PEG fractionation and formalin treatment. The four successive zonal ultracentrifugations decreased virus infectivity by at least 10(7)-fold. Five of these steps tend also to purify the hepatitis B surface antigen (HBsAg) which increases the HBsAg: protein ratio by at least 10(5)-fold. Considering the high degree of purity obtained, checked on each batch, it is concluded that the procedure consistently eliminates any potential virus with a ide safety margin. PMID- 6241770 TI - HBV-vaccination in recipients of kidney allografts. AB - Recipients of renal transplants were vaccinated with 20 ng hepatitis B surface antigen aluminium-adsorbed vaccine in order to gauge their resistance to hepatitis B infection, to which these patients are at high risk. The patients were given three 40 micrograms doses of the vaccine over a period of six months and their antibody titres were measured. Only 9% of patients developed antibodies to hepatitis B and it was established that if possible all patients should receive at least one injection of hepatitis B vaccine prior to surgery. PMID- 6241771 TI - [Hematological methods of occupational screening and detection of latent sensitization in patients with occupational dermatoses]. PMID- 6241772 TI - In vitro antibacterial activity of three new quinolone derivatives: rosoxacin, norfloxacin, pefloxacin. AB - The in vitro activities of rosoxacin, norfloxacin and pefloxacin against 480 bacterial strains were studied. MIC90s of norfloxacin and pefloxacin were less than or equal to 2 micrograms/ml for E. coli, Klebsiella sp., E. cloacae, Proteus sp. and Staphylococcus sp., less than or equal to 8 micrograms/ml for C. freundii, Providencia sp., S. faecalis, and non fermentative Gram-negative bacteria, while they were of 32 micrograms/ml for S. marcescens. Rosoxacin exhibited a lower activity with MIC90s 2 to 16 fold higher against Enterobacteriaceae and P. aeruginosa. Ninety per cent of isolates resistant to nalidixic-acid appeared susceptible to norfloxacin and pefloxacin with MIC less than or equal to 16 micrograms/ml. PMID- 6241773 TI - Enterotoxigenicity of Staphylococcus intermedius strains isolated from dogs. AB - Dogs (n = 100) were examined for the presence of enterotoxigenic Staphylococcus intermedius. Enterotoxigenic strains were isolated from the nasal cavities of 43 (43.0%) out of 100 dogs. Of the 50 enterotoxigenic strains isolated, 23 (46.0%) produced enterotoxin A, 17 (34.0%) enterotoxins A and C, 8 (16.0%) enterotoxin C, and only two (4.0%) enterotoxins A and B. The amount of enterotoxin produced on semisolid brain heart infusion medium by the 17 enterotoxin A producing strains of S. intermedius was 10-160 ng per ml. Enterotoxin A production by S. intermedius strains was ony one tenth to one hundredth of that of S. aureus strains from staphylococcal food poisoning outbreaks. PMID- 6241774 TI - Characterization of coagulase-negative staphylococci from patients with a malignancy compared with those from other sources. AB - 170 strains of coagulase-negative staphylococci isolated from different patient groups have been characterized: 74% were Staphylococcus epidermidis, 18% S. haemolyticus and 7% S. simulans. There were no differences in rates of isolation of the various species from patients with and without a malignancy. Phage typing was not a useful epidemiological tool, but biotyping was possible using the API Staph system. Slime production, a characteristic said to predispose to colonization of catheters, was found to be most common in S. epidermidis strains. PMID- 6241775 TI - [Telethermography in the diagnosis of rheumatic diseases]. PMID- 6241776 TI - [Syndrome of the glenoid ridge in sports medicine]. PMID- 6241778 TI - Suppressor cell induction factor: a new mediator released by stimulated human lymphocytes and distinct from previously described lymphokines. PMID- 6241777 TI - [The acquisition of bipedal gait, evidence of humanization]. PMID- 6241779 TI - [Transmission electron microscopy study of the nasal cilia]. AB - The authors draw the attention on the existence of dyskinetic and immotile cilia in patients with chronic respiratory infections of unknown origin. The study of the ultrastructure of the ciliae is done by a transmission electron microscope. It is very important to make a difference between primary and acquired anomalies. Furthermore, the authors emphasize the importance of early diagnosis in view of a treatment. PMID- 6241780 TI - [Hemodynamic effects of changes in the heart rate]. AB - The effects of the variations in heart rate (HR) within the range of 80 and 180 beats/min were studied in open-chest dogs with complete AV block. Left ventricular systolic pressure (LVSP) and the maximal velocities of development (+P) and fall (-P), left ventricular end diastolic pressure (LVEDP), cardiac output (CO) and duration of ejection (DE) were recorded and analyzed. Contractility was assessed by the force developed by an isometric segment of the left ventricular wall (DT) and the maximal velocities of rise (+T) and fall (-T). Stroke volume (SV), stroke work (SW), stroke power (SP), +P/-P and +T/-T ratios, the time constant of LV pressure fall during isovolumic relaxation (T tau), and mean rate of ejection of left ventricle (MRE) were calculated from the precedent data. LVSP, LVEDP and -P did not show any statistically significant difference, while +P fell by 10 +/- 5% and 16 +/- 4% at 160 and 180 beats/min, respectively. +P/-P ratios were 1.25 +/- 0.07 at 80 beats/min; 1.08 +/- 0.06 at 140 beats/min (P less than 0.01); 1.03 +/- 0.05 at 160 beats/min (P less than 0.01) and 1.02 +/ 0.06 at 180 beats/min (P less than 0.01). CO remained unchanged and due to this SV fell significantly when HR increased. DT, +T, -T, +T/-T and T (tau) were unchanged. DE fell significantly at 120, 140, 160 and 180 beats/min with respect to the initial HR. SW fell significantly at every HR studied. MRE was 147 +/- 13 ml/sec at 80 beats/min and 100 +/- 8 and 93 +/- 7 ml/sec at 160 and 180 beats/min, respectively (P less than 0.01 with respect to control). SP was 161.7 +/- 19.3 g X m X sec-1 at 80 beats/min, and 122.3 +/- 13.2 and 103.8 +/- 9.2 g X m X sec-1 at 160 and 180 beats/min, respectively (P less than 0.01 with respect to control). We may come to the following conclusions: 1) When HR changed in our experimental conditions, CO remained unchanged and due to this the SV fell significantly, showing the difficulty of the heart pump to regulate the CO by itself. 2) The process of relaxation is not affected within the used HR range. 3) In our experiments the inotropic effect due to increments of heart rate ("Bowditch staircase phenomenon") was not detected. However, it might become evident in preparations with more depressed contractility. PMID- 6241781 TI - Suppressive effect of acetylsalicylic acid on erythropoietin-responsive cells in mice. AB - The time-response curve for RBC-59Fe uptake following i.p. injections of 3 doses of 5 mg of acetylsalicylic acid (ASA) at 4 hour interval into normal, nonpolycythemic mice, shows a maximal depression (35% of normal) at 3 days after ASA with return to almost normal values by 7 days. The effect is dose-related, showing a plateau with doses of ASA above 5 mg/4 hr. The shape of the time response curve indicates that the more mature cells in the erythron are not affected by ASA and that the major effect of the drug must be on earlier erythroid cells. Administration of ASA prior to administration of erythropoietin (Epo) into post-hypoxic polycythemic mice depresses the incorporation of 59Fe into erythrocytes. The depression of radioiron uptake is similar when ASA is given prior to or simultaneously with Epo. When ASA is given 24 hr after injection of Epo, suppression is less marked. These results suggest a suppressive effect of the drug on the erythropoietin-responsive cells (ERC). PMID- 6241782 TI - Varying responses of ovum transport in mice related to dose and time of administration of oestradiol. AB - The dose-response relationships between exogenous oestradiol and ovum transport in mice and the effect of treatment on different days of pregnancy were reinvestigated in detail. In addition, serum levels of oestradiol were measured, and their correlation with the various responses was examined. Control animals injected with vehicle alone had the majority of ova in oviductal loops 1 and 2; 3 and 4; or 6 and 7 on days 1, 2, or 3 of pregnancy, respectively. On day four, the majority of ova were found in the uterus. Varying the dose or time of administration of oestradiol determined qualitatively different responses. A single sc injection of oestradiol 5 micrograms or less on day 1 produced scattering of the embryos along the oviduct on day 3 and their accumulation in loops 7 and 8 on day 4, suggesting an increased randomness of the direction of propulsive forces, as well as decreased luminal permeability of the tubo-uterine junction. Doses of 25 and 125 micrograms injected on day 1 caused accelerated transport of ova, some of which entered the uterus as early as 8 hr after treatment. The predominant effect following injection of 1 micrograms on day 2 or days 1 and 2 was acceleration, indicating that oestradiol given on day 2 has opposite effect to and can counteract that of oestradiol given on day 1. Following injection of 25 or 125 micrograms, but not 5 micrograms, on day 1, plasma oestradiol remained significantly elevated through day 2, indicating that tube-locking results from high levels of plasma oestradiol restricted to day 1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 6241783 TI - Changes in plasma aldosterone levels and renin activity after bilateral superior cervical ganglionectomy in two strains of rats. AB - Superior cervical ganglionectomy (SCGx) of Wistar rats brought about a significant increase of plasma renin activity (PRA) 9 or 15 days later, an effect not observed 48 days after surgery. The same surgical procedure performed in Chbb Tom rats did not result in significant modification of PRA. In both strains of rats immobilization stress induced a 2.3-3.3-fold increase of PRA regardless of whether the animals had intact superior cervical ganglia. The injection of the angiotensin-converting enzyme inhibitor captopril to SCGx Wistar rats at the time of elevated PRA induced a severe hypotension, while it did not affect blood pressure in sham-operated animals. In both strains of rats SCGx resulted in depressed circulating aldosterone levels at all studied times after surgery. PMID- 6241784 TI - Evaluation of liver function after thioacetamide treatment of partially hepatectomized rabbits. AB - A group of male rabbits was partially hepatectomized, while another group was administered intraperitoneally with aqueous thioacetamide (TAA) solution (2 mg/kg body weight/alternate day) after partial hepatectomy (PH). The blood samples of animals of both groups were collected on day 10, 15, 20, 30, 60 and 90 following PH and used for various haematological and biochemical analyses. The haemoglobin content decreased significantly within 10 days of PH and gained significant increase 3 months after. An abrupt increase was, however, recorded after TAA treatment. All the enzymatic activities remained unchanged except for that of lactate dehydrogenase (LDH), which was elevated 87% during the first 10 days of PH. The serum glutamate pyruvate transaminase (SGPT) activity was raised 2.8 times. It was only two months after the operation that the alkaline phosphatase (AP) and LDH activities showed signs of inhibition. The only enzyme affected by TAA treatment after the PH was AP activity, which was inhibited drastically within 15 days after operation. It was concluded that, except for the AP activity and bilirubin and urea content, that essentially decreased in the presence of TAA during the first 15-20 days of experimental period, all the other haematological and biochemical parameters got normalized more quickly in the presence of TAA. PMID- 6241785 TI - Ventricular fibrillation threshold in the three-toed sloth (Bradypus tridactylus). AB - The ventricular fibrillation threshold (VFT) can be defined as the minimum electrical value able to trigger fibrillation. The objective was to determine the threshold fibrillatory current in the three-toed sloth, animal which may show spontaneous defibrillation. Ten specimens were used (average weight 3.9 kg, SD 0.28). Two electrodes of the spoon type were laterally applied to the ventricles, stimulating with a nonsynchronized train of rectangular pulses, variable amplitude, until fibrillation was established. Applied voltage and current were displayed on a storage oscilloscope. The average VFT current was 2.3 mA/g of heart (SD 0.4). Each threshold was obtained as the mid-range value between the maximum current which did not fibrillate and the minimum one which did fibrillate. Out of 98 fibrillations, 40% showed spontaneous reversal before 60 sec of fibrillation were completed. Beyond that time, electrical defibrillation was instituted. Three puppies (average weight 5.2 kg, SD 1.4) yielded an average VFT of 0.59 mA/g of heart (SD 0.14) using the same procedure. When the two VFT were compared (unpaired "t"-test), a significant difference was found (t 6.35; p less than 0.001), concluding that sloths would appear as more difficult to fibrillate than dogs of comparable body size. PMID- 6241786 TI - Hypothermia induced by systematically administered epinephrine in the rat. PMID- 6241787 TI - A high-pressure-liquid-chromatography method for the determination of corticosterone in rat plasma. AB - A high-pressure-liquid-chromatography (HPLC), isotope dilution method for the determination of corticosterone in rat plasma is reported. Main characteristics of the technique are: efficient separation of the steroid from 18-HO-DOC and 11 deoxycortisol; two easy pre-purification steps consisting of an acetone extraction-deproteinization and fractionation on Sephadex LH-20; a sensitivity of 5 ng per injection and the possibility of determining 25 ng corticosterone in approximately one milliliter rat plasma. PMID- 6241788 TI - A time-course study of submandibular kallikrein, blood glucose and insulin of alloxan-diabetic and streptozotocin-diabetic rats. AB - A time-course study was carried out of the levels of submandibular kallikrein, serum insulin and blood glucose of rats rendered diabetic by alloxan or streptozotocin. The permanent hyperglycemia seen one day after treatment and the subsequent relative changes in the levels of blood glucose recorded over the following nine days were in agreement with previous observations. A significant reduction in the concentration of submandibular kallikrein did not become apparent until ten days following the injection of alloxan or streptozotocin. Thus the enzyme would not appear to have played either a causal or a preventative role in the production of the hyperglycemic state. Furthermore, in disagreement with previous speculation, the submandibular gland had not compensated for the deficiency of insulin with an increase in production of kallikrein. The fall in the level of serum insulin had preceded the decrease in submandibular kallikrein. However, administration of exogenous insulin over a period of three days did not bring about an increase in the concentration of submandibular kallikrein of the diabetic rats. Thus insulin would not seem to be involved in controlling the level of kallikrein in the submandibular gland. PMID- 6241789 TI - Cisplatinum: a review, with special reference to cellular and molecular interactions. PMID- 6241790 TI - Regression of left ventricular hypertrophy after aortic valve replacement. PMID- 6241791 TI - [Role of positive emotions and emotion-positive brain structures in the regulation of the process of gestation]. PMID- 6241792 TI - [Activity of natural killer cells and the rosette-forming function of peripheral blood lymphocytes in physiological pregnancy]. PMID- 6241793 TI - [Use of integral rheography of the body in obstetrics for the quantitative evaluation of cardiac output]. PMID- 6241794 TI - [Unconjugated estriol levels in the blood of pregnant women with acquired heart defects]. PMID- 6241795 TI - [Echocardiographic characteristics of changes in cardiac chambers in pregnant women with combined mitral valve diseases with predominance of stenosis]. PMID- 6241796 TI - [Folic acid and vitamin B 12 levels in the blood of healthy pregnant women and in patients with anemia of various degrees of severity]. PMID- 6241797 TI - [Use of adrenergic beta receptor blockaders for labor induction]. PMID- 6241798 TI - [Regional blood flow during pregnancy]. PMID- 6241799 TI - [Blood hormone levels in threatened abortion]. PMID- 6241800 TI - [Electroimpulse test as a method for the diagnosis of threatened abortion and to evaluate the effectiveness of treatment]. PMID- 6241801 TI - [Treatment of women habitually aborting]. PMID- 6241802 TI - [Experience with the management of premature labor]. PMID- 6241803 TI - [Effect of induced abortion on the state of the cervix uteri in nulliparae]. PMID- 6241804 TI - [Various aspects of termination of pregnancy by the vacuum-aspiration method]. PMID- 6241805 TI - [Ultrasonic examination in the placental stage]. PMID- 6241807 TI - [Comparative evaluation of various hemostatic indicators in different types of general anesthesia during surgical treatment of patients with uterine myoma]. PMID- 6241806 TI - [State of the breasts in patients with uterine myoma studied by the thermovisual method]. PMID- 6241808 TI - [Value of a rational work schedule for female industrial workers in the prevention of pregnancy complications]. PMID- 6241809 TI - [Clinico-bacteriological characteristics of endometritis after cesarean section]. PMID- 6241810 TI - [Fractionation of seminal and spermatozoal membrane proteins using polyacrylamide gel electrophoresis]. PMID- 6241811 TI - [Premature labor]. PMID- 6241812 TI - [Is meconium admixture in the amniotic fluid a sign of fetal distress?]. PMID- 6241813 TI - [Epilepsy and pregnancy]. PMID- 6241814 TI - [Rehabilitative treatment of climacteric patients after surgical treatment of uterine myoma]. PMID- 6241815 TI - [Habitual abortion of chromosomal etiology]. PMID- 6241816 TI - The isolation of large quantities of undamaged cellular organelles and cytosolic enzymes using a low-shear continuous tissue homogenizer. AB - There is often a need to isolate large quantities of subcellular components such as membrane-coated organelles (e.g., nuclei, lysosomes, and mitochondria), cell membranes, and soluble (cytosolic) proteins. Instruments which can homogenize relatively large masses of tissue, primarily those with rapidly rotating blades and cylinders, are excessively vigorous, often resulting in damaged and/or low yields of the subcellular components. This paper describes procedures for obtaining high yields of undamaged subcellular components using a continuous bulk tissue homogenizer which performs with low shear (the low-shear continuous homogenizer or LSC). This homogenizer is simple in operation, durable and can be used with a variety of tissues. Fibrous tissues are more difficult to homogenize using this instrumentation and require a premincing to small pieces (0.2 to 1.0 cm diam) followed by filtration through 2-4 mesh (two to four apertures per inch). Methods for bulk preparations with enhanced recoveries of undamaged nuclei, and a typical soluble multimeric enzyme, phosphofructokinase, are presented. Electron microscope views of the homogenates show the preserved state of the other subcellular components. The LSC homogenizer requires less physical effort with no "hands on" operation and thus is safer. This homogenizer requires less homogenization time compared to the smaller, hand-held Potter-Elvehjem-type homogenizers. Operations requiring low temperature can be performed at room temperature as long as the continuously passing homogenate solutions are kept chilled. PMID- 6241817 TI - Immunoregulation in multiple sclerosis. PMID- 6241818 TI - Suppressor T cells in MS: do changes in numbers vary with clinical activity? PMID- 6241819 TI - The failure of monoclonal antibody-defined lymphocyte subsets to monitor disease activity in patients with multiple sclerosis. PMID- 6241820 TI - [Treatment of prostatic cancer with an LH-RH agonist: the D Trp6 LH-RH. Preliminary results in 30 cases]. AB - Thirty patients with advanced prostatic cancers (8 stage C, and 22 stage D) were treated for at least three months with D Trp6 LH-RH, a powerful LH-RH agonist. In all the cases in which the testosterone levels had been normal before treatment, the treatment led to a decline to the levels observed after castration. In seven cases, the drop was preceded by a rise in the first few days of treatment. Twenty two patients reacted favorably to the "medical castration" resulting from LH-RH agonists (11 improved and 11 remained stable). The improvements were mainly noted in patients who had not undergone previous treatment. Four deaths were registered in patients already at an advanced stage. Two of these patients presented with visceral metastases in circumstances such that a sudden deterioration due to the agonists cannot be excluded. PMID- 6241822 TI - [Post-thrombolysis intracoronary angioplasty in acute evolving myocardial infarction]. PMID- 6241821 TI - [Effects of administration of a single dose of iprafen (l puff) compared with those of a single dose of ipratropium bromide (40 mcg.) and of fenoterol (100 mcg.)]. PMID- 6241823 TI - Antigen-specific response among T lymphocytes following intestinal administration of alloantigens. AB - The kinetics of T lymphocyte responses to mucosally presented antigen and the appearance of antigen-reactive T cells in mucosal and systemic tissues have been investigated by measuring secondary mixed lymphocyte culture reactivity after intestinal administration of alloantigens. The data indicate that T lymphocytes in the intestine are able to respond to mucosally presented alloantigens, and that following immunisation the T cell reactivity occurs first in Peyer's patches then sequentially in mesenteric lymph nodes, thoracic duct lymph, gut lamina propria and distant mucosal sites. The response was mucosally restricted and the ultimate location of antigen-reactive cells is influenced by site of antigen administration. Evidence is also presented for the existence of systemic nonreactivity to mucosally presented antigens. PMID- 6241824 TI - The relation between technical variation and the mean in the mixed lymphocyte reaction in the rat. AB - Technical variation is a linear function of the incremental mean in the mixed lymphocyte reaction (MLR) and is independent of the immune status of the responders and the gene dose of the stimulators. Logarithmic transformation of the absolute count/control mean makes technical variation independent of the mean. We recommend that this transformation be used before parametric analysis of the data. PMID- 6241825 TI - Effect of an iron-chelating agent on lymphocyte proliferation. AB - The effect of the iron-chelating agent desferrioxamine on lymphocyte proliferation has been studied. Desferrioxamine at concentrations of 15 microM totally inhibited the proliferation of Concanavalin A-stimulated lymphocytes, whereas iron-saturated desferrioxamine was ineffective. Other metal salts, however, had little or no effect on the inhibition induced by this drug. Desferrioxamine was more effective at suppressing proliferation of T lymphocytes than B lymphocytes and additionally suppressed mixed lymphocyte cultures and the generation of cytotoxic T cells. PMID- 6241826 TI - Nickel sensitivity among patients with contact dermatitis: a study at a Bangkok general hospital. PMID- 6241827 TI - Practical approach to vasculitis. PMID- 6241828 TI - Enhancement of cytostatic activity of macrophages against MOPC-315 tumour cells by combined cyclophosphamide administration and immunisation with glutaraldehyde treated tumour cells. PMID- 6241829 TI - H-2 compatibility required for tolerance induction in contact sensitivity to DNFB in allogeneic bone marrow murine chimeras. PMID- 6241830 TI - Immunology of BCG vaccine. PMID- 6241831 TI - Ultrastructure of a temperature-induced Balbiani ring in Chironomus thummi. AB - A Balbiani ring-like structure (T-BR III) is induced at the right telomere on chromosome III by a 35 degrees C heat-shock. The location of T-BR III was identified in 3 micron-semithin sections that were afterwards resectioned to obtain ultrathin sections. These were stained either by uranyl acetate-lead citrate or PTA. The puff appeared composed of different structures: small compact chromatin bodies, loose chromatin with an apparently fibrillar organization, and granules. The granules, 200-250 A in diameter, appeared either in linear arrays or in a clustered form. The three components described above were interspersed within the T-BR without a compartmentalized organization. EDTA preferential ribonucleoprotein staining technique evidenced an EDTA-positive material within the T-BR that corresponded to 200-250 A granules as well as apparently fibrillar structures. However, EDTA did not completely stain some clustered granules. Neither free nor clustered granules were found in T-BRs formed in the presence of actinomycin D. The significance of the different T-BR structures in relation to the transcriptional activity of the puff is discussed. PMID- 6241832 TI - Intra-individual length heterogeneity of Rana esculenta mitochondrial DNA. AB - Mitochondrial DNA extracted from Rana esculenta oocytes appears heterogeneous in size. The length of these molecules varies continuously from 18,700 bp to 19,700 bp. Each animal is heteroplasmic and can be characterized by the range of the variation (400-700 bp) and the extreme sizes of the various molecules it carries. The variable region of the genome has been localized between the coding region and the replication origin area. PMID- 6241833 TI - Changes in protein synthesis and in RNA poly A+ population after treatment of Dictyostelium amoebae by 5-bromo-2'-deoxyuridine. AB - Incorporation of 5-bromodeoxyuridine (5-BUdR) into nuclear DNA severely interrupts the life cycle of Dictyostelium discoideum after the first generation of growth. Loose cellular aggregates are then formed, but no spore or stalk cells are detectable and no other morphological transformations are observed. The perturbation of gene expression in the life cycle has been studied at the protein level by two-dimensional gel electrophoresis after pulse labelling with 35S methionine and also by changes in the patterns of polysomal messenger RNA population. The latter was monitored by hybridisation studies using specific cDNA probes for "vegetative" and "18 hr" messenger RNAs. In the presence of 5-BUdR major anomalies in polypeptide synthesis were observed after the loose aggregation stage. Some vegetative polypeptides, including actin, which are normally abundant only during growth to the aggregation stage, are oversynthesised during the period 12-24 hr after starvation. In this same interval the normal decline in the abundance of vegetative mRNA species was not observed. In marked contrast virtually half the normal "18 hr-specific polypeptides" were poorly synthesised. Likewise, the normal increase in abundance of the corresponding "18 hr-specific" poly A + RNA species in the polysomes did not occur. No major alteration in the timing of the appearance of new macromolecules during the cell cycle was observed in spite of extensive modification of gene expression by the incorporation of 5-BUdR into genomic DNA. PMID- 6241834 TI - Modulation of CALLA and HLA-DR on a non T non B leukemic cell line by lipid treatment. AB - The relationship between membrane lipid fluidity and expression of HLA-DR and cALL (CALLA) antigens was studied in a human non T non B acute lymphoblastic leukemia cell line (Reh). The membrane fluidity was modulated by treatment with cholesteryl hemisuccinate or phospholipids (e.g. egg lecithin) and monitored by fluorescence polarization. HLA-DR and CALLA expression was measured in an indirect immunofluorescence test with a Fluorescence Activated Cell Sorter (FACS 440), on 24, 48, 72 and 96 hour-cultured cells. Significant antigenic modulation was obtained with cholesteryl hemisuccinate treatment on 48 hour-cells where a slight increase in HLA-DR and a marked decrease in CALLA were observed. In contrast no antigenic modification was observed on lecithin-treated cells. PMID- 6241835 TI - Cellular localization of class I (HLA-A, B, C) and class II (HLA-DR and DQ) MHC antigens on the epithelial cells of normal human jejunum. AB - HLA class I and class II (HLA-DR (human I-E equivalent) and DQ (human I-A equivalent] antigens were localized by immunofluorescence technique on thin frozen sections of normal human jejunum using a panel of monomorphic monoclonal antibodies. HLA class I (A, B and C) and HLA-DR molecules were found in the basolateral membrane of enterocytes; HLA-DR were also detected in a patchy distribution in the apical part of enterocytes; HLA-DQ molecules (the human equivalent of the murine I-A molecular subset) were not detected on normal enterocytes. All three molecules were detected on the membrane of lymphocytes and monocytes present in the lamina propria. PMID- 6241836 TI - Role of carbohydrates in rat leukemia cell-liver macrophage cell contacts. AB - The mechanism by which macrophages recognize tumor cells is still unknown. We have studied interactions between rat liver macrophages and rat L 5222 leukemia cells. These tumor cells, but not normal leukocytes or erythrocytes, adhere to freshly isolated macrophages in vitro. Binding of tumor cells by macrophages can be inhibited by N-acetyl-D-galactosamine, D-galactose and more potently by glycoproteins with terminal N-acetyl-D-galactosamine or D-galactose residues. Tumor cell adhesion is calcium-dependent. The relevant leukemia cell membrane structures which bear terminal beta-D-galactosyl or related residues have been determined as trypsin- and pronase-sensitive, and hence may presumably be glycoproteins. The tumor cell receptor on liver macrophages appears to be a lectin with the carbohydrate specificity N-acetyl-D-galactosamine greater than D galactose greater than L-fucose. PMID- 6241837 TI - Intercellular junctions in the hepatopancreas of the lobster Nephrops norvegicus. AB - The hepatopancreas of the lobster has recently been found to be a rich source of material from which to isolate arthopod gap junctions biochemically (Finbow et al., 1983a; 1984). It has therefore been studied here to assess the features of these intercellular junctions and any others that may be present, in vivo. The tissue consists of columnar epithelial cells which possess apical microvilli and basal infoldings. In thin sections the lateral borders of these cells are characterized by desmosomes and smooth septate junctions as well as by gap junctions. The desmosomes exhibit no apparent freeze fracture profile but the septate junctions display parallel rows of ridges or aligned intramembranous particles (IMPs) with complementary grooves on the other membrane half; these IMPs shift in their preferential fracturing plane depending on whether the tissue has first been fixed, always remaining on the EF if unfixed. The IMPs or connexons, of which the gap junctions are composed, fracture onto the E face, leaving complementary pits on the P face, regardless of whether the tissue is fixed or not. At the base of the pancreatic cells, the lateral borders are thrown into interdigitating folds which display endocytotic profiles and possible internalization of junction-bearing membranes. This phenomenon, which is readily visualized both after tracer incubation and in replicas, may represent junctional degradation relating to membrane turnover. PMID- 6241838 TI - Three-dimensional reconstruction of innermost chorion layer from Drosophila melanogaster. AB - A low-resolution three-dimensional structure of the crystalline innermost chorion layer (ICL) has been calculated from electron microscope images of tilted negatively stained crystals. The isolated ICL is a single layer, about 12 nm thick and appears to be made up of two types of subunits, each approximately 3 nm in diameter, arranged regularly as groups of four heterodimers in space group C222. Linking density between these groups of subunits, maintaining the integrity of the layer, appears to be confined mainly to the outer surfaces of the ICL. PMID- 6241839 TI - [Effect of anti-inflammatory drugs on transformation of human T-lymphocytes to blast-like cells induced by PHA and on one-way mixed lymphocyte reaction]. PMID- 6241840 TI - [Arrhythmia following cardiac surgery]. PMID- 6241841 TI - The organization of dental care for groups of medically handicapped children. PMID- 6241842 TI - Qualitative and quantitative measurements of adenosine triphosphatase changes in the brain of mice during low- and high-dose treatment with alpha-chlorohydrin. PMID- 6241843 TI - Autoregulation of the electrogenic sodium pump. AB - The dependence of electrogenic sodium pump activity on changes in the cell volume of Helix pomatia neurons with different levels of intracellular sodium ion concentration was studied. Hypertonic solutions caused hyperpolarization of the membrane and increased membrane resistance in cells with a low sodium content (low-sodium cells; LSC). The activity of the electrogenic sodium pump in hypertonic solutions was increased compared to the activity in hypotonic solutions in LSC and decreased in cells with a high sodium content (high-sodium cells; HSC). The concentration of ouabain which led to maximal inhibition of active 22Na efflux from the neurons was 10(-4) M. Lower concentrations of ouabain (10(-8) M and lower) did not inhibit the sodium pump but stimulated it. The swelling of neurons in hypotonic solutions was accompanied by an increase in the number of binding sites for ouabain, while shrinking in hypertonic solutions led to the opposite effect--a decrease in binding sites. An increase in the number of binding sites also took place in normal isotonic potassium-free solutions compared with normal Ringer's solution. Two saturable components of ouabain binding were detectable in all solutions examined. gamma-Aminobutyric acid (GABA) and acetylcholine (ACh) increased the number of ouabain binding sites on the membrane. The results suggest that there are two opposite mechanisms by which cell volume changes can modulate the pump activity. One of them depends on the intracellular sodium ion concentration and causes pump activation in hypertonic solutions in LSC and saturation in HSC, while a second mechanism mediates the activating effect of cell swelling on the sodium pump in HSC. In addition, there may be a negative feedback between the pump activity and the number of functioning pump units in the membrane. PMID- 6241844 TI - [Epidemiological survey of viral hepatitis among a hospital staff]. PMID- 6241845 TI - Hemostatic disorders in 25 patients with limited and uncomplicated thyroid and breast cancer: prophylactic and therapeutic considerations. AB - In order to evaluate the efficacy of an anticoagulant treatment in neoplasia, we have looked for the existence and the possible role of hemostatic unbalance in patients affected by limited and uncomplicated thyroid and breast cancer by examining hemostasis in 25 patients. Our data allowed us to evidentiate an accelerated and increased fibrinoformation associated with the presence of plasminogen's activation inhibitor which overlaps the increased plasminogen's activators. We evidentiated also an increase of platelet functions in vitro and of their activation in vivo. These findings support the hypothesis of a possible role played by hemostasis alterations in the pathogenesis of thromboembolic complications, cancer growth and/or metastatization, and justify prophylactic and therapeutic anticoagulation. PMID- 6241846 TI - Clinical trial of combined hormone therapy (MAP + TAM) for metastatic breast cancer. AB - High dose MAP (medroxyprogesterone acetate) and TAM (tamoxifen) were administered orally to 31 postmenopausal patients with advanced breast cancer. CR (complete remission) was achieved in 1 (3%) and PR (partial remission) in 11 (32%) patients for a median duration of 12 months. The treatment was well tolerated and in no instance was interrupted because of toxicity. This study does not support the hypothesis that the combination of MAP and TAM gives better results than the single agents. PMID- 6241847 TI - In vitro activity of pefloxacin compared to that of quinolones and other antimicrobial agents. AB - Pefloxacin is a new methyl-4-piperazinyl quinolone. It had MIC90 values of less than 0.01 to 0.8 micrograms/ml for the majority of Escherichia coli, Klebsiella, oxytoca, Citrobacter, Providencia, Enterobacter cloacae, Enterobacter aerogenes, Morganella and Proteus mirabilis. It inhibited ampicillin, cephalexin and nalidixic acid resistant isolates of these species. Against Pseudomonas the pefloxacin MIC90 was 3.1 micrograms/ml. Staphylococcus aureus had a MIC50 of 0.4 micrograms/ml and a MIC90 of 0.8 micrograms/ml and S. faecalis had a MIC90 of 3.1 micrograms/ml. Pefloxacin inhibited Salmonella spp., Salmonella typhi, Shigella spp., Yersinia, Aeromonas, toxigenic E. coli at concentrations of less than 0.05 to 1.6 micrograms/ml, including ampicillin and trimethoprim resistant strains. There was a minimal difference in MIC and MBC values in broth or serum, but major changes in MIC and MBC values occurred in acid urine. Increase in MIC values occurred with repeated transfer in broth or urine. PMID- 6241848 TI - Oral route administration of medroxyprogesterone acetate (MAP) at high doses in the treatment of advanced breast cancer: clinical results. AB - Twenty-six patients with metastatic breast cancer were treated with high dose medroxyprogesterone acetate (MAP) p.o. according to currently available pharmacokinetic data (2000 mg/day b.i.d. for 30 days, 1000 mg/day for the following 60 days). Objective response (WHO criteria) was obtained in seven patients (CR + PR = 27%), with good results on visceral and soft tissue localizations; performance status improvement and/or pain relief was obtained in twenty-three (88%). Oral high dose MPA seems to be an effective and well tolerated palliative treatment in advanced breast cancer. PMID- 6241849 TI - The effect of high dose medroxyprogesterone acetate on water and salt metabolism in advanced cancer patients. AB - Ten advanced cancer patients (both with hormone-sensitive and non-hormone sensitive tumors) were treated with high dose medroxyprogesterone acetate (MAP, greater than 500 mg/day). We determined body weight, lean body mass, blood pressure, sodium blood level, urinary excretion, and exchangeable sodium pool by the 22Na method before and after treatment. These data seem to exclude a fluid retentive effect for high-dose MAP. PMID- 6241851 TI - Human and rat atrial natriuretic polypeptides (hANP & rANP) purification, structure and biological activity. PMID- 6241850 TI - Evaluation of progress using the context input process and product model. AB - Most evaluations of programme effectiveness are based on process data (the data generated by the programme) and used for internal monitoring and service development. Context (the ecology of therapeutic systems), input (the identification of what is in fact different between two therapeutic systems) and product (the consequence of different inputs, taking account of context) evaluations are rarely, if ever, produced. In this paper (using input and product evaluations) the progress of twelve Down's syndrome and twelve multiply handicapped children attending, over a period of 18 months, two different therapeutic systems operated by the New Zealand Society for the Intellectually Handicapped (Auckland Branch/outside Auckland Branches) is assessed. The progress of the Auckland children is significantly better in a number of areas than for those outside Auckland. This improvement in progress can be attributed to input differences that reflect the Auckland Branch's policy of service development. The most important determinants of a successful programme are not staff/student ratios, time in class or specialist assistance, all of which favour the outside Auckland groups, but the degree of structure, detail of programmes and assessments, and quality of parent contact in which Auckland seems superior. The results for the Down's syndrome group compare favourably with those from other Down's syndrome programmes. PMID- 6241852 TI - Biological activity of a synthetic alpha-human atrial natriuretic polypeptide in anesthetized dogs. PMID- 6241853 TI - Effects of high and low molecular weight atrial natriuretic factor in the isolated kidney. PMID- 6241855 TI - T-inducer lymphocytes, leukapheresis and the pathogenesis of rheumatoid arthritis. PMID- 6241854 TI - Lymphapheresis in rheumatoid arthritis. The clinical and laboratory effects of a limited course of cell depletion. AB - Five patients with active rheumatoid arthritis refractory to conventional therapy were treated with a limited course of lymphapheresis--6 procedures during a two week in-hospital stay. Statistically significant improvements in assessments of rheumatoid activity were apparent by 2 weeks following lymphapheresis and persisted for 10-12 weeks. An average of 2.08 X 10(10) lymphocytes were removed from the patients and lymphopenia appeared in the 4 in whom the average daily rate of removal exceeded 1 X 10(9). However, the results of laboratory testing indicate that immuno-suppression, as based on evaluations of skin test reactivity to delayed hypersensitivity antigens and on the proportion of T cells following lymphapheresis, was not required for therapy to be deemed effective. PMID- 6241856 TI - Defective expression of OKT4 antigen on the cell surface of helper T lymphocytes in a patient with systemic lupus erythematosus. AB - OKT-monoclonal antibodies directed to total T-cells (OKT3), inducer/helper (OKT4) or suppressor/cytotoxic (OKT8) T-cells recognize developmental antigens on human T-cells. We report here an 18 year old male patient with systemic lupus erythematosus who had a prominent decrease in the proportion of OKT4-reactive T cells in his peripheral blood, although the proportion of OKT3- and OKT8-reactive T-cells were essentially normal. His peripheral blood lymphocytes (PBL) responded well to stimulation by phytohemagglutinin-P (PHA) or concanavalin-A (Con A), which are stimulators for OKT4-reactive T-cells or for both subsets. Furthermore, helper T-cell function for B-cell proliferation was demonstrable in the patient's T-cells which lacked both OKT4 and OKT8 antigens. Trypsinization of PBL from healthy individuals abrogated detection of the OKT4 antigen, and a complete recovery of the antigen was observed after 6 days of culture of the treated PBL. The OKT4 antigen, however, could not be expressed on the patient's PBL after this treatment and incubation. In addition, the patient's serum could not block the recovery of OKT4 antigen on trypsinized T-cells from healthy individuals. The decrease in the percentage of OKT4-reactive T-cells was relatively stable in the patient, while his clinical disease activity and medications were variable. Taken together, these results suggest a defective expression of OKT4 antigen on the helper T-cell subset in this patient. PMID- 6241857 TI - Saturable, high-avidity monocyte receptors for monomeric IgG and Fc fragments increase in SLE and lyme disease. AB - We have devised an assay for quantifying high-avidity Fc receptors for monomeric IgG on peripheral blood monocytes. In the development of a radiolabelled ligand for the assay, we found that Fc fragments offer several advantages over 7S-IgG. Compared to the latter ligand, the fragments interacted more cleanly with a single high-avidity binding site, appeared to have easier access to this site, and, since they showed no binding to Millipore filters, their use made possible a wash procedure that was convenient and rapid, thus minimizing loss of specifically bound ligand. Application of the assay to a study of ten normal controls, five patients with SLE, and three patients with Lyme disease demonstrated that normal monocytes bear approximately 10,000 high-avidity binding sites per cell. In contrast, patient monocytes bore significantly more Fc receptors; on average their cells had about 40,000 such sites per cell (P = 0.01) and sometimes as many as 100,000 sites per cell. Both normal and patient monocytes bound IgG or Fc fragments with an apparent association constant (KA) of approximately 10(8) M-1. The majority of patients with active SLE and Lyme disease had serum C1q-binding material compatible with the presence of circulating immune complexes. This study shows that these putative circulating immune complexes do not necessarily lead to a reduction in the number of Fc receptors on peripheral blood monocytes. Rather, the data suggest that in the course of immune mediated diseases, either monocytes are activated in vivo to express greater numbers of Fc receptors, or a subset of monocytes bearing more Fc receptors is expanded. PMID- 6241859 TI - Hypogammaglobulinaemia in systemic lupus erythematosus: report of a case with evidence for spontaneously activated T suppressor cells. AB - A patient with hypogammaglobulinaemia associated with systemic lupus erythematosus (SLE), a healthy HLA-A, B, C, D-identical and mixed lymphocyte culture (MLC)-negative sibling, and two mutually HLA-A, B, C, D-identical siblings were investigated. Blood mononuclear cells from the patient contained a high proportion of T lymphocytes with the suppressor/cytotoxic phenotype, and in vitro no development of Ig-secreting cells was observed in response to pokeweed mitogen (PWM) or to Epstein-Barr virus (EBV), as opposed to cell cultures from the siblings. In cell cultures from the two healthy HLA-identical siblings, T lymphocytes as well as monocytes/macrophages (M phi's) could be replaced with corresponding cells from the sibling without major alterations of the pokeweed mitogen (PWM)-induced B cell response. In PWM-stimulated co-cultures of B cells from the patient with healthy HLA-identical T cells, moderate numbers of IgM secreting cells developed, but not IgG- or IgA-secreting cells. T cells from the patient co-cultured with healthy HLA-identical B cells suppressed their Ig secretion; this effect was abolished by irradiation of the T cells. The in vitro generation of T suppressor cells by concanavalin A (ConA) was normal. No evidence for abnormal suppressor function of monocytes/macrophages was obtained. Thus in this patient, spontaneously activated T suppressor cells as well as defective B cells were associated with hypogammaglobulinaemia. PMID- 6241858 TI - Sjogren's syndrome presenting with hypereosinophilia, lymphopenia and circulating immune complexes. AB - Although mild peripheral eosinophilia is a common finding in Sjogren's syndrome (SS), severe eosinophilia with a clinical picture simulating hypereosinophilic syndrome is extremely rare. We report a 24 year old male with SS presenting with swelling of the parotid glands, redness and irritation of the eyes, polyarthralgias and polyarthritis, weight loss, exertional dyspnea, malaise, erythematous and urticarial skin lesions and enlarged lymph nodes. Laboratory tests showed hypereosinophilia (34%, total 3800/mm3), lymphopenia (2%, total 220/mm3), a positive RA factor (1:2560) and decreased C3 and C4. Biopsy of an enlarged submaxillary gland was consistent with SS. A Schirmer test showed decreased tear production. Salivary glands showed a marked decrease in uptake of radioactive (Tc99) dye. Circulating immune complexes (CIC) were markedly elevated by both C1q binding and Raji cell assays. T-cell subsets showed OKT3 = 63%, OKT4 = 32% and OKT8 = 16%. "Histamine trap" in vivo test for CIC revealed fluorescence in upper dermal blood vessels with IgM, C1q, C3 and fibrin. Biopsies of the liver, bone marrow and skin revealed eosinophilic infiltration. A notable response to therapy with high doses of corticosteroids was seen with recurrence of symptoms and laboratory abnormalities after the therapy was stopped. In conclusion, we present a case of SS which is remarkable for the age and sex of the patient, extreme hypereosinophilia, marked lymphopenia, and CIC. PMID- 6241860 TI - Helper (OKT4)/suppressor (OKT8) ratios in the peripheral blood and synovial fluid of patients with rheumatoid arthritis. AB - Lymphocyte subsets in the peripheral blood of 10 patients with RA were studied using monoclonal antibodies. The mean percentages of total T, T helper, T suppressor and TAR in the peripheral blood of RA patients were not different from those observed in normal controls. In the synovial fluid the mean percentages of T suppressor cells were present in increased numbers associated with a decreased number of autorosette T cells. We conclude that patients with rheumatoid arthritis present distinct immunoregulatory abnormalities in the synovial fluid not present in the peripheral blood. These changes may be related to the immune abnormalities present and related to the etiology of RA. PMID- 6241861 TI - Immunological studies of the arthritis of acne conglobata and hidradenitis suppurativa. AB - The etiology and pathogenesis of acne arthritis and the arthritis of hidradenitis suppurativa remain unknown. Some patients have an asymmetrical pauciarticular arthritis compatible with the 'reactive' peripheral and central forms of Reiter's syndrome, whereas others have a symmetrical polyarthritis/polyarthralgias syndrome. The cutaneous disease is clinically manifest as acne conglobata or hidradenitis of axilla or groin. We determined human leukocyte antigens (HLA), levels of immunoglobulins, C3, C4 and circulating immune complexes from six patients with acne arthritis. Four of six patients had HLA antigens of B7 Creg group (B7, BW22, B27, BW40, BW42) and all six possessed DRW4. Isolated elevations of immunoglobulins, C3 and C4 were observed. Immune complexes were elevated uniformly. These observations suggest that immunogenetic mechanisms may play a role in the systemic manifestations of these skin diseases. PMID- 6241862 TI - Suppressor cell deficiency and elevated circulating immune complexes in familial Mediterranean fever. PMID- 6241863 TI - [Late observations of changes in Concise fillings in children and adolescents]. PMID- 6241865 TI - [Computed tomography in the diagnosis of hepatic cavernous hemangioma with a report of 20 cases]. PMID- 6241864 TI - [Evaluation of the maintenance of repaired fractured tooth crowns in children using composite materials and Palavit 55]. PMID- 6241866 TI - [Studies on 102 normal roentgenograms of the thoracic duct (discussion of lymphangiographic criteria for the diagnosis of thoracic duct obstruction)]. PMID- 6241867 TI - [Radiologic anatomy of the hilar angle of the right lung]. PMID- 6241868 TI - [Radiological observation on pulmonary edema due to phosgene poisoning]. PMID- 6241869 TI - [Gray scale ultrasonic manifestations of breast tumors (an analysis of 71 cases)]. PMID- 6241870 TI - [Radiological diagnosis of Budd-Chiari syndrome (report of 12 cases)]. PMID- 6241871 TI - [Radiologic diagnosis of multiple foci carcinoma of the esophagus (report of four cases)]. PMID- 6241872 TI - [Roentgen anatomy and normal variations of the celiac artery (analysis of 96 cases)]. PMID- 6241873 TI - [Measurement of the extrahepatic bile duct diameter by ERCP in normal Chinese subjects]. PMID- 6241874 TI - [X-ray diagnosis of malignant meningioma and meningeal sarcoma (an analysis of 23 cases)]. PMID- 6241875 TI - [Angiographic observation on traumatic intracranial hematoma & its complications]. PMID- 6241876 TI - [Tuberous sclerosis (a report of 10 cases)]. PMID- 6241878 TI - [TPS isodose curve in the treatment of nasopharyngeal carcinoma]. PMID- 6241877 TI - [X-ray diagnosis of non-ossifying fibroma of the bone (analysis of 30 cases)]. PMID- 6241879 TI - [Advances in radiation technics]. PMID- 6241880 TI - [The X-ray tomography machine and its application]. PMID- 6241881 TI - [Preliminary study on a new variant of a platelet aggregation defect]. PMID- 6241882 TI - Effect of angiotensin II on secretion of adrenal androgens. AB - To assess the effect of angiotensin II (A II) on the secretion of human adrenal androgens (AA), plasma dehydroepiandrosterone (DHEA), DHEA sulfate (DS) and delta 4-androstenedione (delta 4-A) were measured in eight normal men 60 and 120 min after stimulation of endogenous A II by a bolus injection of 40 mg frusemide, and the direct effect of A II on the secretion of adrenal androgens was examined in cultured human adrenocortical cells in the presence of a low concentration of ACTH. The administration of frusemide led to a significant increase in the plasma DHEA and DS concentration as well as plasma renin activity (PRA) and aldosterone concentration (PAC), but did not change plasma cortisol and delta 4-A. In the culture of human adrenocortical cells, 10(-9)-10(-5) M A II or 10(-13) M ACTH alone did not stimulate the secretion of DHEA, DS and delta 4-A, while 10(-7) and 10(-5) M A II in the presence of 10(-13) M ACTH caused a significant increase in DHEA and DS secretion with no change in delta 4-A. These results suggest that the activated renin-angiotensin system stimulates the secretion of adrenal androgens by a direct effect of A II on adrenal cortical cells. PMID- 6241883 TI - Symposium on biology of cardiac overload. 7-9 July 1983, Jouy-en-Josas, France. PMID- 6241884 TI - Distribution of myosin isozymes in human atrial and ventricular myocardium: comparison in normal and overloaded heart. AB - We have prepared monoclonal antibodies specific for either atrial or ventricular myosin and defined the isomyosin composition of myocardium in normal and overloaded human hearts. In the atrial myocardium, normal isozymic pattern was V1 dominant which converted to being V3 dominant in an overloaded condition. In contrast, normal isomyosin pattern of the ventricular myocardium was exclusively V3 dominant, and only a small change in the proportion of isomyosin was observed in an overloaded condition. From this, we conclude that isozymic changes in cardiac myosin could occur in the human heart to meet increased work induced by cardiac overload. However, the physiological importance of these isomyosin redistributions in human myocardium seems to be much greater in the atrium than in the ventricle, since larger amounts of V1 isomyosin which could be transformed to V3 isomyosin were present in the atrial myocardium. PMID- 6241885 TI - Characterization and distribution of myosin variants in normal and pathological human hearts. AB - Hybridomas were prepared from mice immunized with myosin from the enlarged left ventricle of a 53-year-old female bearing an obstructive cardiomyopathy. With several different experimental approaches using anti-myosin antibodies, at least two subpopulations of atrial and at least two subpopulations of ventricular myosin were detected, characterized and located in normal human hearts. The human atrium and human ventricle each contained small zones of myosin variation which were scattered, but probably not randomly distributed, within a large area of myocardium whose cellular distribution of myosin was constant. Recent applications of the same approach to the study of the regional variations of the different myosin forms within two pathological human hearts are discussed. PMID- 6241886 TI - Contractile protein transitions in human cardiac overload: reality and limitations. AB - Attention has focused on possible defects at the level of the contractile proteins in myocardial hypertrophy and failure. In small mammals such as the rat and rabbit, myofibrillar and myosin ATPases are depressed in situations of decreased contractility. Converse increases in enzymic activity together with enhanced contractility are seen in the hyperthyroid state. The molecular basis for these changes in enzymic activity is now known to result from transitions in three heavy chain isoenzymes of myosin, V1, V2 and V3 which possess different ATPase activities. Transitions in isoenzyme composition occur during hypertrophy, thyrotoxicosis and development in the myocardium of small mammals. In larger animals such as the rhesus monkey, baboon, cow and in particular, man, only V3, the lowest ATPase isoenzyme can be detected in the normal ventricle and this is the only form present throughout development. Confirmation of the lack of developmental transitions in myosin heavy chains expressed in man is also obtained by sensitive peptide mapping techniques. Changes in myosin heavy chain isoenzymes in large mammals as an explanation of depressed contractile function cannot therefore be made on the presently available evidence. Indeed, evidence for lowered ATPase activities in the failing human myocardium is equivocal. Evidence is however provided for transitions in light chain isoenzymes of myosin in situations of cardiac overload. Caution should be exercised in using small animals as models of myocardial hypertrophy and failure in man. PMID- 6241887 TI - The hypertrophied myocardium accumulates the MB-creatine kinase isozyme. AB - Myocardial hypertrophy was produced in the dog by volume overload, secondary to hypertension, and pressure overload to left or right ventricles and in the rat by pressure overload to the left or right ventricles, by elevating thyroxine-levels and secondary to spontaneous hypertension in order to test whether there are changes in the creatine kinase system in hypertrophied heart. Although there was little or no change in total creatine kinase activity, there were changes in the distribution of the creatine kinase isozymes. In the dog, a 4-10-fold increase in the tissue content of MB-creatine kinase was observed for heart chambers with a 40-90% increase in the ratio of ventricular weight to body weight. In the rat, MB creatine kinase also accumulated in hypertrophied ventricles. For the spontaneously hypertensive rat, the correlation between increased fetal creatine kinase isozymes and increased ratio of ventricular weight to body weight was excellent (r approximately 0.92). During the transition from compensated hypertrophy to failure in the spontaneously hypertensive rat, there is a 50% decrease in mitochondrial creatine kinase activity. P-31 NMR magnetization transfer experiments suggest that flux through the creatine kinase reaction is 3 fold lower than normal in these failing hearts. These results show that there are changes in the distribution of the creatine kinase isozymes in hypertrophied heart and suggest that one of these changes characterizes compensated hypertrophy (increased fetal-type creatine kinase isozymes) while another characterizes the transition to failure (decreased mitochondrial creatine kinase). PMID- 6241888 TI - Cardiac alterations at the myofibrillar level: is a redistribution of the myosin isoenzyme pattern decisive for cardiac failure in haemodynamic overload? AB - Cardiac muscle physiology, cardiac dynamics and energetics of normotensive and hypertensive rats [Goldblatt II, spontaneously hypertensive rats (SHR)] are analyzed in the light of the question of whether a shift in the isoenzyme pattern of myosin in favour of the isoenzyme VM-3--i.e., transformation towards a slower muscle--is the essential factor for manifestation of cardiac insufficiency under chronic haemodynamic overload. Earlier investigations on chemically skinned myocardial preparations with homogeneous VM-3 and VM-1 patterns revealed that the decrease in unloaded shortening velocity attributable to extreme redistribution of the isoenzyme pattern can amount to approx. 40% whereas isometric tension development at the myofibrillar level is not significantly reduced. Findings from old normotensive and spontaneously hypertensive rates show that even substantial prevalence of VM-3 permits adequate ventricular pumping function. The decrease in the systolic parameters observed in later stages of chronic pressure overload may be attributed primarily to regressive alterations (fibrosis, structural dilatation). Under chronic haemodynamic overload, experimentally imposed isoenzyme redistribution towards a faster myocardium (small thyroxine doses) as well as transformation towards a slower muscle (thyrostatic treatment) affects the time parameters of contraction and oxygen consumption more than left ventricular work capacity. Signs of congestive heart failure are absent. It is concluded that mere transformation of myocardium towards a more slowly functioning muscle should not be considered the cause of cardiac failure in the rat model although this adaptive process may have detrimental consequences under certain conditions. PMID- 6241889 TI - Aortic pressure, substrate utilization and protein synthesis. AB - An increase in aortic pressure from 60 to 120 mmHg in Langendorff perfused hearts increased oxygen consumption, glucose utilization, pyruvate oxidation and protein synthesis. These changes were not prevented by insertion of a ventricular drain that prevented intraventricular pressure development. Arrest of the heart with tetrodotoxin markedly reduced oxygen consumption; under these conditions an elevation of aortic pressure did not increase oxygen consumption. Elevation of aortic pressure in arrested-drained preparations supplied either glucose or pyruvate as oxidizable substrate increased protein synthesis to a comparable extent. Energy availability, as assessed by measurements of the creatine P/creatine ratio, increased as aortic pressure was raised in hearts provided glucose, but not pyruvate, suggesting that greater energy availability was not the factor linking higher aortic pressure to faster rates of synthesis. These results focus attention on stretch of the ventricular wall, as the mechanical factor responsible for the effects of aortic pressure on several metabolic activities of the heart. PMID- 6241890 TI - Pyrimidine nucleotide metabolism in cardiac hypertrophy. AB - Cardiac hypertrophy was induced in rats either by isoprenaline treatment or by experimental abdominal aortic stenosis. In both models, the UTP content increased in the hypertrophying heart, while the ATP level remained depressed. The rate of net synthesis of uracil nucleotides, estimated by phosphate incorporation into alpha-phosphate groups, was largely increased during the first stage of hypertrophy (X 3.6 and 2.6, respectively). At identical stages of hypertrophy, the rate of synthesis of ribosomal RNA, measured after continuous intracardiac infusion of 3H-uridine, was increased by 1.6 and 2.5 times. A comparison of the changes in time course of the levels of UTP and RNA and their turnover suggests that the metabolism of uracil nucleotides and that of ribosomal RNA are closely interrelated. The increase in the rate of synthesis of pyrimidine is interpreted as an adaptational change in nucleotide metabolism in response to the increased requirement of precursors for RNA synthesis. The possible limiting role of pyrimidine nucleotides in the hypertrophic process is discussed. PMID- 6241891 TI - Cardiac contractile protein synthesis: does the pattern change in stress? PMID- 6241892 TI - Cardiac myosin heavy chain isozymic transitions during development and under pathological conditions are regulated at the level of mRNA availability. AB - We have shown that the level of two ventricular MHC mRNAs, fetal and adult, can account for the observed isozymic transitions of the myosin protein during normal development and under pathological conditions. Moreover, these MHC mRNAs are encoded by two genes that are linked in the genome, less than 5 kilobases apart and are organized according to their developmental expression. The fact that the two ventricular MHC genes are very closely related at the nucleotide sequence level, and yet respond in opposite direction to the same stimulus, makes these genes an excellent model in which to study the possible mechanisms involved in the gene switching. PMID- 6241893 TI - Myosin heavy chain mRNA during the development and regression of myocardial hypertrophy. AB - RNA synthesis increases during the development and decreases during the regression of pressure-overload induced myocardial hypertrophy. Until now, we have been unable to determine whether these events actually reflected changes in the messenger RNAs for the myosin heavy chain mRNA in the total RNA extracted from rat heart during the development and regression of hypertrophy. We found that the amount of MHC mRNA increased in proportion to the overall increase in total RNA during the development of hypertrophy. However, upon relief of pressure overload, MHC mRNA decreased to a much greater degree than did total RNA. This is probably related to a sudden cessation of synthesis and the rapid degradation of mRNA. We conclude that the development and regression of myocardial hypertrophy is a function of changes in the mRNA for contractile proteins. PMID- 6241894 TI - Isomyosins, microtubules and desmin during the onset of cardiac hypertrophy in the rat. AB - Chronic overloading of the rat heart induces a cascade of adaptational events which compensate for the increase in work. Two of these have been extensively described: a qualitative event with an isomyosin change leading to an improved efficiency and a quantitative event resulting in cardiac hypertrophy. By means of immunofluorescence, we investigated if elements of the cytoskeleton, i.e. microtubules and intermediate filaments, could be triggers for these adaptational mechanisms. Studies of overloaded heart were performed in young rats with aortic stenosis or adult rats with aortic insufficiency. Cardiac myocytes were isolated and labelled by immunofluorescence with antibodies raised against V1 or V3 isomyosin, desmin or tubulin. The aim of the work was to visualize: when and where the shift in the expression of isomyosins occurs within the myocytes; the eventual changes in the pattern of intermediate filaments of desmin and/or of microtubules during the adaptation of myocytes to overload. We observed: that the shift from the high (V1) to low (V3) ATPase isomyosin occurred in a population of myocytes soon after stenosis; that changes in the pattern of microtubules occurred soon after induction of hypertrophy; no changes in the distribution or intensity of the staining of desmin. PMID- 6241895 TI - The ultrastructure of myocardial hypertrophy: why does the compensated heart fail? AB - Several qualitative features of the ultrastructure of pressure overload and thyrotoxic myocardium are unique markers of the type and quantity of increased work the heart has been required to perform. Furthermore, they are reminiscent of features of normally growing myocytes, implying that the changes in the hypertrophied cell are the consequence of normally present capacities for adaptation to a demand for increased myocardial work. Thyrotoxic myocardium has two features which distinguish it from normal and pressure overloaded hearts: the mitochondria are large and have a peculiar fragile or lacey appearance. Many myocytes show considerable disorganization of sarcomeric myofilaments. Pressure overloaded hearts have smaller and more numerous mitochondria than the normal myocyte. Their sarcomeres have thicker Z bands than controls. Double intercalated discs are also a feature of these myocytes. Several features of hypertrophied myocytes are seen in both types of hypertrophy: RER and ribosomes on the external nuclear membrane. There are polyribosomes aligned along the long axes of thick filaments, presumably involved in myosin synthesis or transformation within the cell. There are areas of sarcomerogenesis both under the sarcolemma and within the cell at the intercalated disc. These are characterized by fragments of myofilaments, polyribosomes and rough endoplasmic reticulum. Quantitatively, myocyte composition is transiently disturbed but, like that of normally growing hearts, returns to control values as the adaptation to stress is negotiated. PMID- 6241896 TI - Overall myocardial energetics in physiological conditions and in acute volume overloading. AB - Left ventricular heat production (PH,lv) was compared with myocardial O2 consumption (P met O2) and mechanical parameters in intact anaesthetized dogs before and after acute volume overload induced by a perfusion of LMW dextran. From myocardial blood flow and coronary arterio-venous temperature differences, the coronary heat loss was determined. Thermodilution techniques were used to estimate the ratio between heat carried away by the coronary system and total heat production as the left ventricular volumes. Compared with P met O2, PH,lv bore a linear correlation. Heat production per beat was highly correlated to mean systolic wall force, midwall circumferential length, midwall fibre shortening and mean circumferential shortening rate (MCSR). Mechanical efficiency computed from heat production (EH) appeared to be very close to the efficiency computed from oxygen consumption (EO). Acute overload was characterized by a very large increase in both stroke volume and MCSR. The dramatic increase observed in heart external power was accompanied by a moderate increase in PH,lv and mechanical efficiency. Nevertheless, the changes in efficiency appeared to be strongly dependent upon the changes observed in heart rate (HR). When HR was increased, the heat production per beat was moderately decreased and efficiency was drastically improved. Conversely, dogs in which HR remained stable exhibited a marked increase in the energetic cost of each beat, with efficiency being practically unmodified. Thus, since myocardial energetics is involved in acute volume overload, two possible means of adaptation may be considered: (a) tachycardia may alleviate the energetic cost of each beat, thus improving heart mechanical efficiency and (b) conversely, if HR remains stable, it may do so at the expense of the energetic cost of the myocardium for each beat, with efficiency not actually being enhanced. PMID- 6241897 TI - Myocardial cell nucleus in cardiac overloading in the rat. AB - The myocardial cell nucleus was studied in the rat during its normal growth and under different types of heart overloading. Under overloading of short duration, a disappearance of condensed chromatin and an increase in the nucleolus and nucleolonema were interpreted as representing cell overactivity. With isoproterenol overloading, a first stage of cell necrosis and of its consequences on chromatin and nucleolus was followed by the process of cell repair and overactivity. With overloading of long duration, several different nuclear aspects were encountered: (a) enlarged and distorted nuclei as possible supports of polyploidy; (b) a partial coupling between two adjacent nuclei, interpreted either as nuclear fusion or amitosis; (c) segregation of different proteins, probably due to cell damage. The number of nuclei per myocyte was high (90%) in the adult. It decreased (80%) two days after isoproterenol overloading, as well as in heart hypertrophy of 6-9-months duration. Nuclear size increased under isoproterenol overdosage of 48-h duration. The amount of nuclear DNA also increased two days after isoproterenol overdosage, particularly in mononucleated cells. PMID- 6241898 TI - A myothermal analysis of the myosin crossbridge cycling rate during isometric tetanus in normal and hypothyroid rat hearts. AB - Hypertrophied rabbit heart papillary muscles (thyrotoxicosis), with a high V1/V3 myosin isoenzyme ratio and contractile protein ATPase activity, have a high velocity of unloaded shortening and a decrease in the myothermal economy of isometric twitch force development and dissipation; in hypertrophied hearts (pressure overload) with a low V1/V3 isoenzyme ratio and ATPase activity, the converse was found to be true (Am J Cardiol 1979; 44:947-953; Fed Proc 1982; 41:192-198). In the present study the confounding problem of internal shortening, which takes place during force development and dissipation in the isometric twitch, is minimized by carrying out measurements of the rate of heat liberation during the plateau phase of tetanic force maintenance. The studies are further extended to another species (rat) where the V1/V3 myosin isoenzyme ratio is altered by treating the animal with propyl thiouracil added to the drinking water (PTU); here the contractile protein alteration occurs with myocardial atrophy rather than hypertrophy. High resolution, rapid temperature measurements are made in tetanically stimulated isometrically contracting rat heart papillary muscles from normal (high V1/V3 ratio) and PTU treated (low V1/V3 ratio) rats to assess the relationship between contractile protein performance (crossbridge cycling rate) in the intact muscle and that under controlled conditions in isolated myofibrils. In papillary muscles from the normal heart the crossbridge cycling rate (+/- SEM) during force maintenance was 6.53 (+/- 1.73) cycles/second compared with 3.13 (+/- 0.24) and 0.53 (+/- 0.17) cycles s-1 in the myofibril at high and low ionic strength, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 6241899 TI - Electrophysiologic properties of hypertrophied myocytes isolated from rats with renal hypertension. PMID- 6241900 TI - Protective effects of cardioplegia on diastolic function of hypertrophied rat hearts after hypothermic ischaemic arrest. AB - This study was undertaken to assess the effects of hypothermia and chemical cardioplegia on the functional recovery of hypertrophied non-failing rat hearts subjected to an extended period of global ischaemia. Left ventricular hypertrophy was produced by constriction of the abdominal aorta. Hearts were studied an average of 8 weeks following this procedure. Sham-operated animals served as controls. Twenty-nine isolated isovolumic perfused rat heart preparations were then subjected to 2 h of ischaemic arrest at 15-18 degrees C followed by 45 min of normothermic reperfusion. In one series of hearts (8 sham, 8 hypertrophied), myocardial protection consisted of hypothermia alone. In another series (6 sham, 7 hypertrophied), repeated infusions of cardioplegic solution at 30-min intervals throughout arrest were added to hypothermia. Hypothermia alone resulted in a similar preservation of contractility as evidenced by the recovery of dp/dtmax/left ventricular (LV) systolic pressure after 45 min of reperfusion (91.6 +/- 5.9% of control values in sham vs 78.6 +/- 6.5% in hypertrophied hearts). Conversely, the recovery of compliance was much more impaired in hypertrophied hearts as indicated by a significantly higher percentage of increase in post-ischaemic LV diastolic pressure (DP) (at 45 min of reperfusion: 243.8 +/- 27.5% of control values vs 167.1 +/- 23.8% in sham, P less than 0.05). The addition of cardioplegia improved the preservation of contractility in both groups but its major effect was to normalize the recovery of compliance in hypertrophied hearts so that post-ischaemic LVDP values were no longer different from those recorded in normal hearts (at 45 min of reperfusion: 102.1 +/- 32.8% vs 98.5 +/- 14.2% of pre-ischaemic values respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 6241901 TI - Relaxation of mammalian heart muscle during chronic cardiac overload. AB - Cardiac relaxation was studied in rat papillary muscle during hypertrophy induced by different chronic volume and/or pressure overload (aortic insufficiency, aorto caval fistula, aortic stenosis, spontaneously hypertensive rat). Maximum velocity of lengthening did not depend upon the degree of cardiac hypertrophy, but rather on the type of chronic overload. Cardiac hypertrophy did not modify the load sensitivity of relaxation, whatever the type and stage of chronic overload, although, during acute hypoxia, the load sensitivity disappeared both in normal and in hypertrophied heart muscle. PMID- 6241902 TI - Myocardial function structure and collagen in the spontaneously hypertensive rat: progression from compensated hypertrophy to haemodynamic impairment. PMID- 6241903 TI - Reversal of left ventricular hypertrophy and improvement of cardiac function in man by nifedipine. AB - The effects of long-term (mean 3.9 months) pharmacotherapy of hypertensive and normotensive hypertrophy (hypertensive heart disease, hypertrophic non obstructive cardiomyopathy) as well as of advanced cardiac disease due to coronary artery disease and dilatative cardiomyopathy by large doses of nifedipine (mean 120 mg/day-1) were analyzed with regard to systolic blood pressure, to left ventricular function and to the hypertrophy degree of the ventricle. Nifedipine, in addition to conventional and maintained antihypertensive and cardiac therapy, lowers blood pressure in hypertensive patients, whereas hypotensive effects in the normotensive patients were absent. Nifedipine enhances left ventricular function in all patient groups significantly, i.e. in normotensive hypertrophic non-obstructive cardiomyopathy, in hypertensive heart disease and especially in heart disease due to coronary artery disease and dilatative cardiomyopathy. Significant regression of septal and of global hypertrophy was found in hypertrophic non-obstructive cardiomyopathy and in hypertensive heart disease. These results indicate, that long-term nifedipine treatment may be beneficial for left ventricular function in all patient groups and for hypertrophy regression in established left ventricular hypertrophy due to hypertrophic, non-obstructive cardiomyopathy and due to hypertensive left ventricular hypertrophy. It is concluded that long-term nifedipine treatment improves left ventricular function and leads to regression of established ventricular wall hypertrophy in hypertrophic non-obstructive cardiomyopathy and in hypertensive heart disease. PMID- 6241904 TI - Correlation of myosin isoenzyme alterations with myocardial function in physiologic and pathologic hypertrophy. AB - To explore the interactions of physiologic and pathologic hypertrophy, four groups of hearts were studied in an isolated working rat heart apparatus. Cardiac contractile proteins were also evaluated. The groups were hearts of female control sedentary rats; rats subjected to a 10-week swimming programme; rats with renal hypertension; and hypertensive rats subjected to a 10-week swimming programme. The swimming programme in normotensive female rats caused a 30% cardiac hypertrophy, in hypertensive animals 46% hypertrophy, and in combined hypertension and swimming 70% hypertrophy. Ca2+-myosin ATPase activity and actin activated myosin ATPase were elevated in hearts of swimmers, depressed in hearts of hypertensive sedentary animals and similar to control values in hearts of hypertensive swimmers. Myosin V1 isoenzyme content was increased in hearts of swimmers, depressed in hearts of hypertensives, but normal in hearts of hypertensive swimmers. Reciprocal relationships were seen with the V3 isoenzyme. Stroke work, mean velocity of circumferential fibre shortening, and per cent fractional shortening at the midwall showed increased values for hearts of swimmers, depressed values for hearts of hypertensives, and normal values or values above the control for hearts of hypertensive swimmers. Myocardial flow measured with microspheres was increased in the left ventricle of swimmers, depressed in hearts of hypertensives and still depressed in hypertensive swimmers, but significantly higher than in the hypertensives alone. The correlation of actin-activated ATPase activity and of fractional shortening was linear among the four groups. These studies demonstrate that physiologic and pathologic hypertrophy in the rat have distinctly opposite effects on contractile proteins and contractile performance. When one type of hypertrophy is superimposed on the other the effects are additive. PMID- 6241905 TI - Left ventricular isomyosins in normal and hypertrophied rat and human hearts. AB - Regulation of rat cardiac contractility by changes in the expression of a particular form of myosin (V1-V3) has been demonstrated with a pressure overload. Previous reports of the effect of a volume overload have been controversial. Therefore, we measured the isomyosin composition and mechanical function in the same papillary muscles from rat hearts subjected to a chronic volume overload (aortic insufficiency, AI). A marked change in isomyosin composition from V1 to V3 occurred. Contractility, as assessed by shortening velocity Vmax, was also significantly decreased, and this decrease was correlated with the isomyosin transformation. The changes in isomyosin composition and speed of contraction with AI are thus similar to changes induced by aortic stenosis. Little experimental evidence exists for involvement of such changes in the regulation of human cardiac contractility. Using immunoglobulins highly specific for V1 and V3 in autopsy samples we have observed that the human left ventricle is mostly composed of a V3 isoform (HV3) and that small amounts (1 to 15%) of a V1 type (HV1) are present in foetal and some adult hearts. This HV1 is absent from the left ventricles of patients with valvular disease, assessed at the time of valve replacement (N = 30, samples provided by Dr P. Menasche). Myosin Ca2+-stimulated ATPase activities were not significantly different between normal and hypertrophied hearts. These data demonstrate the heterogeneity of human ventricular myosin, which is composed of V1 and V3 isomyosins, as in other mammalian species. Isomyosin shifts from V1 to V3 are possible in man, but they are quantitatively small and without noticeable influence on overall ATPase activities. PMID- 6241906 TI - Myosin isoenzymes in human hypertrophic hearts. Shift in atrial myosin heavy chains and in ventricular myosin light chains. AB - The myosin light chain complement and proteolytic peptide patterns of myosin heavy chains were studied by two-dimensional and one-dimensional electrophoretic techniques respectively, in a total of 57 samples from ventricular and atrial tissues of normal and hypertrophied human hearts. Hypertrophies were classified haemodynamically as due to pressure-overload and volume-overload. In addition to the occurrence of ventricular light chains in hypertrophied atria we also observed the atrial light chain-1 (ALC-1) in hypertrophied ventricular tissues. On average over 6% of total light-chain-1 comprised ALC-1 in pressure-overloaded ventricles and around 3% in volume-overloaded ventricles. In single cases of pressure-overload ALC-1 amounted up to over 20% of total light chain-1. With regard to the myosin heavy chains limited digestion by two different proteinases produced over 200 clearly resoluble peptides. The absence of any detectable differences in the peptide patterns between myosin heavy chains from normal and hypertrophic tissues of left or right ventricle is in line with the findings of J. J. Schier and R. S. Adelstein (J Clin Invest 1982; 69: 816-825). In atrial tissues however, reproducible qualitative differences in the peptide patterns indicated that during hypertrophy a different type of myosin heavy chains becomes expressed. No differences were seen between the myosin heavy chains from normal left and right atria. PMID- 6241907 TI - Myosin changes in hypertrophied human atrial and ventricular myocardium. A correlated immunofluorescence and quantitative immunochemical study on serial cryosections. AB - Two antigenically distinct types of myosin heavy chain, referred to as alpha and beta, have been identified in autoptic and bioptic specimens of human heart using specific antimyosin antibodies. By immunofluorescence heavy chain alpha was present in all atrial myocytes and in a variable number of ventricular myocytes. Heavy chain beta was present in all ventricular myocytes and in a number of atrial myocytes. Ventricular hypertrophy in patients with aortic stenosis, systemic hypertension or tetralogy of Fallot was characterized by an almost complete absence of fibres reactive with anti-alpha. A striking decrease in alpha chain reactivity and a parallel increase in beta chain reactivity was apparent in the hypertrophied left atria of patients with mitral stenosis. To quantify these myosin changes a novel procedure was developed whereby myosin was extracted from single cryosections serial to those processed for immunofluorescence and the relative amount of alpha and beta heavy chain was determined by enzyme immunoassay. Heavy chain alpha was less than 5% in most normal ventricular specimens and disappeared completely under the effect of pressure overload. On the other hand heavy chain beta was generally undetectable in the left atrial myocardium but increased up to 90% in biopsies of hypertrophied atria. PMID- 6241908 TI - [Effect of adaptation to a hot climate on thermoreceptor function]. PMID- 6241909 TI - [Strategy for mental adaptation to Antarctic conditions]. PMID- 6241910 TI - [Correlation between electrocardiographic and echocardiographic findings in chronic aortic insufficiency]. AB - Echocardiographic indices of left ventricular volume and mass and electrocardiographic indices of left ventricular hypertrophy have evaluated in 25 patients with chronic aortic regurgitation and in 10 normal subjects. When the patients with aortic regurgitation were subdivided in three groups with increasing evidence of left ventricular hypertrophy, the echocardiographic measures of left ventricular dimension and mass were also found to be increased, with statistically significant differences between patients and controls and among the three groups of patients as well. A specially constructed cumulative electrocardiographic index of left ventricular hypertrophy (Sokolow and Lyon's index plus Lewis' index plus strain pattern) is correlated with the left ventricular end-diastolic diameter (r = 0.65; P less than 0.001), cross-sectional area (r = 0.65; p less than 0.001) and mass (r = 0.75; p less than 0.001) better than the isolated electrocardiographic indexes. PMID- 6241911 TI - [The pressure-dimension curve and midwall stress. Use of a combined hemodynamic echocardiographic method and correlation with contrast ventriculography]. AB - An invasive (left ventricular pressure recording) and a noninvasive technique (M mode echocardiography) were combined during the hemodynamic study of 15 patients with various degrees of left ventricular impairment, in order to provide left ventricular function parameters independent from contrast studies. Left ventricular pressure, dimension and wall thickness changes were continuously digitized on a computer system, which was able to derive the ventricular pressure dimension loop and to calculate the midwall equatorial stress at end-diastole and peak-systole. The parameters derived from the loop (diastolic work, net systolic work, cycle efficiency) and midwall meridional and circumferential stresses were compared with the results of contrast ventriculography and with the wall hypertrophy index. Diastolic work appeared to be correlated with the systo diastolic volume change; systolic work correlated with the ejection fraction; the cycle efficiency was inversely correlated with both end-diastolic and end systolic volumes and directly correlated with the hypertrophy index. Midwall stress, both end-diastolic and peak-systolic, was strongly and positively correlated with ventricular volumes, while it decreased with increasing hypertrophy. Systolic stress increased with decreasing ejection fraction. The combined echo-pressure technique, through the evaluation of the pressure dimension loop and the calculation of wall stress, can generate data of left ventricular function that allow a more complete assessment of left ventricular impairment. PMID- 6241912 TI - [Relation between asymmetrical hypertrophy of the interventricular septum and plasma levels of catecholamines in normotensive chronic uremic patients undergoing hemodialysis treatment]. AB - Sympathetic-adrenergic activity has been evaluated in 23 chronic uremic, normotensive patients on regular hemodialysis, 7 of which (30.4%) with M-mode and bidimensional echocardiographic finding of asymmetric septal hypertrophy. The sympathetic function has been assessed by measuring arterial plasma norepinephrine and epinephrine levels before and after postural activation, just before and after dialysis. After dialysis, standing caused a significant increase of plasma norepinephrine levels in patients with asymmetric septal hypertrophy in comparison with patients without asymmetric septal hypertrophy and with the control non uremic group. Moreover, a significant decrease in blood pressure and a sharp heart rate increase were noted in the patients without asymmetric septal hypertrophy, whereas mean blood pressure and heart rate were unchanged in the patients with asymmetric septal hypertrophy. These results suggest that increased plasma norepinephrine concentration may have a role in the development of interventricular septal hypertrophy. PMID- 6241913 TI - [Josamycin in the treatment of acne]. PMID- 6241914 TI - Growth of the young heart: influence of nutrition and stress. AB - Newborn rat pups reared in litters of 4 and 16 inhaled up to 500 ppm carbon monoxide for 14 days, while others in litters of equal size remained in room air. Body weight, combined ventricle weight, hemoglobin concentration, hematocrit, and myocardial DNA content were measured. Differences in hemoglobin concentration and hematocrit between the four groups of pups were small. Cardiomegaly resulting from CO-stress was intensified in pups from small, as opposed to large litters. Relative combined ventricle weight was unaltered by change in litter size in the absence of CO-stress, although combined ventricle weight and body weight were increased with small litter size. Ventricular DNA content, indicative of cellularity, was increased in small litters and with CO-stress. Exacerbated postnatal anemia is not responsible for the differential effects of litter size and stress on the heart. PMID- 6241915 TI - Heterogeneity of beta-thalassemia in Azerbaidzhan. AB - Globin chain synthesis, RNA and DNA of beta-thalassemic patients from Azerbaidzhan were analyzed. A beta-mRNA deficiency was found in beta + thalassemic reticulocytes. In one case of beta +-thalassemia, it was possible to study nuclear and cytoplasmic RNA from spleen erythroid cells. The alpha/beta mRNAs sequence ratio was 5 in the nuclear and cytoplasmic RNAs. In patients with beta o-thalassemia a different level of beta-globin mRNA was demonstrated. Gene mapping analysis indicated that the general organization of the beta-globin gene was normal in the investigated cases of beta-thalassemia. PMID- 6241916 TI - Enzyme activities of hepatic glucose utilization in the fed and fasting genetically obese mouse at 4-5 months of age. AB - Activities of key enzymes in hepatic glucose utilization were compared between obese (C57BL/6J ob/ob) mice, their lean controls and outbred Swiss albino mice in the fed condition and during fasting. As liver hyperplasia and hepatocyte hypertrophy were present in the ob/ob mice at 4-5 months of age and changes in hepatic cellularity did occur with fasting, enzyme activity was expressed on the basis of protein, DNA, and wet weight. In the fed state, activities of glucokinase + hexokinase (glucose phosphorylating capability), phosphofructokinase and pyruvate kinase were significantly greater in livers of ob/ob mice when compared to those of the lean control. Glucokinase + hexokinase activities in livers of ob/ob mice remained significantly higher throughout the 48 h fast yet the activities of hepatic phosphofructokinase and pyruvate kinase, when expressed per g wet wt or mg protein, decreased so that a statistical difference from the fasted lean control was no longer detected. When expressed per 100 g body weight, hepatic glucokinase + hexokinase as well as phosphofructokinase and pyruvate kinase activities in obese mice were higher both in the fed and fasted states when compared to lean controls in the comparable nutritional condition. This increased capacity of key enzyme activities in hepatic glucose utilization can be attributed to liver hyperplasia found in ob/ob mice in both the fed and fasted condition. While higher hepatic glucose phosphorylating capability was maintained during fasting, the elevated specific activities of hepatic phosphofructokinase and pyruvate kinase in the obese mouse in the fed state decreased with starvation to values found in the lean control. PMID- 6241917 TI - Amelioration of streptozotocin-induced diabetes in the rat by exercise-training: role of muscle glycogenolytic and glycolytic enzyme activity. AB - Streptozotocin-induced insulin deficient rats allowed to run at will had significantly (P less than 0.001) lower mean (+/- SEM) plasma glucose levels (12.1 +/- 0.9 vs 22.6 +/- 1.7 mM/l) than did equally insulin deficient sedentary rats. Muscle glycogen phosphorylase and synthase activities were similar in exercise-trained and sedentary diabetic rats, and were unchanged from control values. In contrast, muscle phosphofructokinase activity was reduced (P less than 0.001) in sedentary rats with insulin deficiency, and the defect was significantly reversed (P less than 0.01) when such rats were allowed to run spontaneously. These results are consistent with the view that the ability of exercise-training to attenuate the magnitude of hyperglycemia in streptozotocin induced insulin deficiency is associated with an effect on a key regulatory enzyme in the glycolytic pathway. PMID- 6241918 TI - [Demonstration of C3-binding circulating immune complexes using Raji, conglutinin and anti-C3 assays--a critical review]. AB - There remains no doubt at the present time, that the appearance of circulating immune complexes in illness accompanying vasculitis and for glomerulonephritis correlates with the severity of disease. Moreover, immune complexes are of diagnostic importance where infections with a chronic development or neoplastic diseases are concerned. The choice of IC test system should incorporate their essential biological functions and identify those IC that activate the complement cascade both by the classical and the alternative route. The detection of IC bound C3 cleavage products (C3b, C3bi, C3d) represents the key to identification of a wide range of IC. Of the presently available methods Raji cell test, conglutinin- and anti C3-IC assay, on critical appraisal, the anti C3-IC assay represents the most applicable way of defining complement binding IC. The advantage of this system is that appreciable disturbances and limitations that influence other systems do not affect the antigen-antibody reaction which is the core of the anti C3 assay. PMID- 6241919 TI - [The C3 activating capacity in human serum--measured as monocyte mediated chemiluminescence]. AB - Phagocytosing monocytes form activated oxygen species which can be detected by the luminol-mediated chemiluminescence (CL). C3b-coated particles yield enhanced CL-signals due to their binding to the monocytes' C3b-receptor. Thus, the zymosan induced monocyte-CL in a medium containing fresh or heat-inactivated serum provides a means of measuring in sera the capacity to activate C3. PMID- 6241920 TI - [Long-term changes in the immune system following cytostatic polychemotherapy in patients with testicular tumors in remission]. AB - Patients who received combination chemotherapy for metastatic nonseminomatous testicular cancer showed a decreased Con A induced suppressor cell function. Additionally 15% of the patients who received ifosfamid had a decreased IgM-serum concentration, an increased number of macrophages and a decreased proliferation rate in MLC. PMID- 6241921 TI - Wheat germ agglutinin decreases expression of the T8 antigen on human peripheral mononuclear cells. AB - We examined dynamics of expression of the human T-suppressor specific antigen, T8, following interaction of peripheral lymphocytes with wheat germ agglutinin (WGA). Cells were incubated at 37 degrees C with or without WGA (15 micrograms/ml) for 18 hrs, washed sequentially with N-acetylglucosamine (to remove bound WGA) and plain medium, then analyzed by flow cytometry for binding of lectins and monoclonal antibodies OKT8(T-suppressor specific) and OKT3 (pan-T specific). WGA pretreatment induced an overall 65% reduction in WGA binding and concomitant 30% reduction in percentage of T8+ cells. Furthermore, residual T8+ cells showed 50% reduction in T8 expression. Taking into account reductions in both percentages of T8+ cells and also antigen densities, WGA reduced T8 expression by greater than 60% overall. By contrast, binding of OKT3 and the lectins, concanavalin A (con A) and Ricinus communis agglutinin (RCA-I), was unaffected by WGA. The decreased T8 expression could not be explained by residual cell bound WGA and was fully reversible within 48 hours of removal of cells from WGA-containing medium. Therefore, WGA caused downregulation of T8 antigen expression. The effect of WGA was time- and concentration-dependent. Downregulation did not occur at 4 degrees C nor in the presence of azide, thereby demonstrating a requirement for cellular metabolism. The data suggest that WGA may bind to the T8 antigen, and they provide the possibility that similar downregulation of T8 by WGA may underlie certain of the in vitro immunoregulatory effects of this lectin. PMID- 6241922 TI - Identification of proliferating lymphocyte subpopulations in microcultures by surface marker and autoradiography. AB - A micromethod is described which allows subpopulation classification of proliferating (3H thymidine incorporating) cells, previously stimulated in microcultures. The technique is based on transferring 1,000 to 5,000 cells from microcultures to poly-L-lysine coated multispot slides. The cells are then stained for surface markers using the immuno-peroxidase method, combined with subsequent autoradiography. PMID- 6241923 TI - Dissociation of stimulatory capacity in mixed lymphocyte reaction and proliferative responses to pokeweed mitogen among peripheral blood non-T cells. AB - The stimulatory capacity in mixed lymphocyte reaction (MLR) and responsiveness to pokeweed mitogen (PWM) by peripheral blood non-T cells were studied. E rosette- and adherent cell-depleted lymphocytes were divided into low, medium and high density populations using discontinuous Percoll gradient. Low density non-T cells were potent stimulators in both autologous and allogeneic MLR despite low proliferative response to PWM. In contrast, those with medium density showed weaker stimulation in autologous though not in allogeneic reactions and underwent strong blastogenesis in PWM cultures. Non-T cells with high density had low MLR stimulatory capacity and yet manifested the highest stimulation indices on PWM stimulation. These findings suggest that functional characteristics of non-T cells may be separable on the basis of cell density. PMID- 6241924 TI - Prevention and treatment of virus hepatitis B. PMID- 6241925 TI - Clinical effects of nickel. PMID- 6241926 TI - Medical and toxicological aspects of occupational nickel exposure in the Federal Republic of Germany--clinical results (carcinogenicity, sensitization) and preventive measures (biological monitoring). AB - In recent years reports on nickel-related diseases in the Federal Republic of Germany have been increasingly frequent. As a result, medical scientific institutions were called upon to clarify both the occupational medical and clinical, as well as the toxicological aspects of the situation. The main clinical finding was the increased incidence of malignant neoplasias in the respiratory tracts, in particular after many years of nickel exposure in refineries. Between 1967 and 1981, seven malignant neoplasms were legally recognized as occupation-related. Additionally, in the last two years, the existence of nickel-induced malignant neoplasms has been suspected in 16 cases, and the statutory procedure for the recognition of occupational diseases instituted. Our overview presents occupational-medical and clinical aspects. Among allergic nickel-induced conditions, eczematous skin diseases predominate. In addition, case reports of asthma have been published. Statistical evaluations showed that up to 17% of all occupational allergies may be related to occupational exposure to nickel. In this situation, preventive measure are of particular importance. To estimate exposure levels, both the measurement of the agent at the workplace and the quantitative determination of nickel in biological material can be used. The measurement of nickel excretion by the kidney has proved particularly useful in occupational medicine. In addition to clinical surveillance, it is recommended that this measurement should be performed on exposed persons at regular intervals. PMID- 6241927 TI - Human exposure to nickel. AB - In order of abundance in the earth's crust, nickel ranks as the 24th element and has been detected in different media in all parts of the biosphere. Thus, humans are constantly exposed to this ubiquitous element, though in variable amounts. The average natural nickel exposure from food in the past has probably been somewhat, but not much, below current levels. Nickel is a useful metal, particularly in various alloys, in batteries and in nickel-plating. Nickel compounds are used especially as catalysts and pigments. In nickel-producing or nickel-using industries, about 0.2% of the work force may be exposed to considerable amounts of airborne nickel. In addition, nickel release, e.g., into cutting oils, and skin contact with nickel-containing or nickel-plated tools and other items may add to an occupational nickel hazard. Occupational exposures may lead to the retention of 100 micrograms of nickel per day. Environmental nickel levels depend particularly on natural sources, pollution from nickel manufacturing industries and airborne particles from combustion of fossil fuels. Absorption from atmospheric nickel pollution is of minor concern. Vegetables usually contain more nickel than do other food items; high levels have been found in legumes, spinach, lettuce and nuts. Certain products, such as baking powder and cocoa powder, have been found to contain excessive amounts of nickel, perhaps related to nickel leaching during the manufacturing process. Soft drinking-water and acid beverages may dissolve nickel from pipes and containers. Leaching or corrosion processes may contribute significantly to the oral nickel intake, occasionally up to 1 mg/day. Scattered studies indicate a highly variable dietary intake of nickel, but most averages are about 200-300 micrograms/day. In addition, skin contact to a multitude of metal objects may be of significance to the large number of individuals suffering from contact dermatitis and nickel allergy. Finally, nickel alloys are often used in nails and prostheses for orthopaedic surgery, and various sources may contaminate intravenous fluids. Thus, human nickel exposure originates from a variety of sources and is highly variable. Occupational nickel exposure is of major significance, and leaching of nickel may add to dietary intakes and to cutaneous exposures. Preventive efforts should mainly be directed towards adequate control of these exposure sources. PMID- 6241928 TI - Effect of ascorbic acid and some reducing agents on N-nitrosopiperidine metabolism by liver microsomes. AB - The effect of ascorbic acid on the oxidation of N-nitrosopiperidine by a microsomal preparation obtained from guinea-pig liver has been examined. The metabolites from the oxidation of N-nitrosopiperidine were found to be 5 hydroxypentanal (about 1.93%), N-nitroso-3-hydroxypiperidine (about 0.02%), and N nitroso-4-hydroxypiperidine (about 0.15%). With microsomes separated from the liver of guinea-pigs pretreated with phenobarbital and 3-methylcholranthrene, the yields of N-nitroso-3-hydroxypiperidine and N-nitroso-4-hydroxypiperidine were found to decrease upon increasing the concentration of ascorbic acid in the reaction mixture. In the presence of small amounts of ascorbic acid, the yields of these compounds with untreated liver microsomes apparently increased, while the presence of larger amounts of ascorbic acid caused a decrease in the yields of these metabolites. In contrast with the yields of N-nitroso-3 hydroxypiperidine and N-nitroso-4-hydroxypiperidine, that of 5-hydroxypentanal decreased with increasing amounts of ascorbic acid. PMID- 6241929 TI - Genetic and biochemical factors affecting the induction of bacteriophage lambda by N-nitroso compounds. AB - As part of our effort to validate a biochemical (prophage) induction assay (BIA) as a screening test for carcinogens, we have tested more than 100 N-nitroso compounds. An enzyme, beta-galactosidase, is induced as an indirect consequence of DNA damage to the host, as part of the 'SOS' response. Besides the obvious practical importance of detecting this class of carcinogen, there is the question of the mechanism by which these compounds work. Mutagenesis by one compound, N methyl-N'-nitro-N-nitrosoguanidine, is known to proceed by both SOS (recA) dependent and SOS-independent pathways. Mispairing due to O6 alkylation of guanine is thought to be responsible for the SOS-independent pathway; however, there has been little consideration of recA-dependent functions, of which phage induction is one. Although nitrosamides could be detected as phage inducers in our assay, N-nitrosamines in the presence of rat liver 9 000 X g supernatant usually gave no response. We found that the use of several mutant strains, particularly a lexA mutant, in combination with hamster liver 9 000 X g supernatant, allowed us to detect most N-nitrosamines reasonably well, in either a spot test or a quantitative tube assay. Induction in a lexA strain was most unexpected, since this mutation usually diminishes the expression of SOS functions induced by ultra-violet light. Because the genetic and biochemical conditions that favour phage induction are different from those that favour mutagenesis, it seems likely that the lesions in DNA leading to the two biological end-points are different. PMID- 6241930 TI - A phase 1 study of recombinant interferon-gamma given intravenously by portable mini-pump: a preliminary report. AB - Recombinant interferon-gamma was given to patients with tumours by a six-hour intravenous infusion using a portable mini-pump, to assess the side-effects of the drug. At present, 11 patients have been treated; 2 adenocarcinoma of the ovary, 3 squamous carcinoma of the bronchus, 1 adenocarcinoma of the breast, 1 adenocarcinoma of the stomach, 1 Hodgkin's lymphoma, 1 case of two primaries, adenocarcinoma of the breast and ovary, and 1 adenocarcinoma of unknown origin. Two patients received 1 X 10(6) units/m2/infusion, four received 3 X 10(6) U/m2/inf., three received 6 X 10(6) U/m2/inf. and two received 9 X 10(6) U/m2/inf. Two further dose levels will be used in the future; 27 and 51 X 10(6) U/m2/inf. Three 6-hour infusions a week were given for a four week period. The major side-effects of gamma-interferon were dose-related pyrexia with rigors to which there was no tachyphylaxis, acute and chronic tiredness, nausea with or without vomiting, headache, backache and myalgia. There was also a dose-dependent immediate but mild and transient decrease in the total white cell count. All effects have been transient, and none have been severe. We have also noticed that intravenous infusions by mini-pumps are tolerated far better by the patients than conventional drip systems, and we feel mini-pumps are the ideal way to give intravenous infusions. PMID- 6241931 TI - In situ subpopulations of lymphocytes in human colorectal carcinomas. AB - Subpopulations tumour-infiltrating lymphocytes were studied in 13 patients with colorectal carcinoma using cryostat immunohistochemistry. Murine monoclonal antibodies (MAB) to the surface phenotype of lymphocyte subpopulation were used in an indirect immunoperoxidase method to demonstrate T (MAB OKT3), T helper (MAB OKT4), T suppressor (MAB OKT8) and B lymphocytes (MAB B1). Langerhans cells were demonstrated using MAB OKT6. All cells reacting with each monoclonal antibody were more prevalent in the stroma of the tumour than within the sheets of malignant cells. In both these areas, OKT8-positive cells were significantly more numerous than OKT4-positive cells, as estimated quantitatively by point counting on a fixed grid. In uninvolved areas of normal mucosa, OKT4-positive lymphocytes were in the majority. OKT6-positive cells were present in large numbers within tumour cells and in close association with lymphoid aggregates. The presence of large numbers of OKT8-positive cells in situ in human colorectal carcinomas may be a cellular mechanism in favour of tumour growth. OKT6-positive cells in situ suggest that mechanisms for antigen processing and presentation are well represented in human colorectal carcinomas. PMID- 6241932 TI - Unique calcium-dependent hydrophobic binding proteins: possible independent mediators of intracellular calcium distinct from calmodulin. AB - Calcium-dependent regulation of cellular processes is mediated by specific intracellular proteins. A newly described set of proteins isolated from chicken gizzard with Mr of 67 X 10(3), 35 X 10(3), 33 X 10(3) and 30 X 10(3) also express a hydrophobic site in the presence of calcium. These proteins are isolated from several other cellular tissues and are termed calcimedins. These proteins differ from calmodulin in isoelectric point, DEAE-cellulose binding characteristics and heat stability. The calcimedins do not activate calmodulin-dependent cyclic nucleotide phosphodiesterase but do activate a hepatic microsomal Ca2+ -ATPase system. Hence, the possibility is opened that calcium regulation of cellular processes is mediated by calcium-binding proteins in addition to calmodulin. PMID- 6241935 TI - [Current status of pulsed Doppler method]. PMID- 6241934 TI - Decreased aldosterone receptor affinity in aortic cells from the Fischer 344 rat. AB - The Fischer 344 rat strain represents a uniform population that is immune to salt induced hypertension and resistant to mineralocorticoid hypertension. We have compared aldosterone binding in aortic cells cultured from salt-resistant Fischer 344 rats to that from salt-sensitive Wistar-Kyoto controls for aldosterone binding. Aortic smooth muscle cells of both strains contain two classes of aldosterone binding sites: corticoid receptor I with high affinity and low capacity and corticoid receptor II with low affinity and high capacity. The corticoid receptor I of Fischer 344 rats has a significantly (P less than 0.001) lower affinity than that of age and sex-matched Wistar-Kyoto controls, but the binding capacity was the same. There was no difference between the strains in the affinity or binding capacity of corticoid receptor II. These results indicate that mineralocorticoid binding may be important in susceptibility and resistance to hypertension and support the contention that mineralocorticoids regulate blood pressure in part by direct action on vascular smooth muscle cells. PMID- 6241936 TI - [Measurement of aortic blood flow and its clinical application]. PMID- 6241937 TI - [Symposium on mechanisms of host defense from fundamental and clinical medicine. 4. Significance of autologous mixed lymphocyte reaction-activated immune circuits for maintaining normal immune homeostasis in humans]. PMID- 6241933 TI - Iodination of myofibrils and myosin. AB - The relative reactivity of the tyrosine side chains in the proteins of skeletal muscle myofibrils was determined using iodination techniques. The destruction of ATPase activity of myofibrils and myosin by lactoperoxidase and chloramine-T iodination could be prevented by the attachment of cysteamine to the sulphydryl groups prior to the iodination reaction and subsequent regeneration with thioglycolate or dithiothreitol. Iodination using 1,3,4,6-tetrachloro-3 alpha, 6 alpha-diphenylglycoluril did not require cysteamine treatment for retention of full enzymatic activity. The specific activity of the different proteins varied markedly with desmin, troponin-T, and tropomyosin having the highest labelling with all three iodination procedures. In contrast the myosin light chains had low specific activity when labelled in myofibrils or intact myosin. The isolated light chains, however, were much more highly iodinated. It appears that iodination may be a useful technique for examining protein-protein interactions in the myofibril. PMID- 6241938 TI - [Symposium on mechanisms of host defense from fundamental and clinical medicine. 5. Genetic control of immune response in humans and its clinical significance]. PMID- 6241939 TI - [Comparative studies on characteristic structures of sensory and motor mechanisms in the stomatognathic system of the pangolin, Manis aurita (Mammalia). Part 1. Masticatory muscle and their spindle supply in the pangolin]. PMID- 6241940 TI - A programme for the construction of a lambda phage. AB - Infection of a sensitive host by the lambdoid coliphages can cause death of the bacterial cell by lysis or can lead to a lysogenic cell, with the viral DNA stably integrated into the host chromosome. These alternative responses both require the coordination of several host and phage functions, and lambda infection follows a well controlled developmental plan. The lytic and lysogenic pathways of lambdoid infection are reviewed, with emphasis on the variety of control mechanisms involved in the commitment to a particular pathway. PMID- 6241941 TI - A flavone with antiinflammatory activity from the roots of Rhus undulata. PMID- 6241942 TI - [Quantitative determination of gallotannin in Paeoniae Radix]. PMID- 6241943 TI - Intravenous "conscious" sedation in periodontal surgery. A selective review and report of 1,708 cases. PMID- 6241944 TI - [Suppressor activity of OKT4+17+ cells from patients with adult T-cell leukemia]. PMID- 6241945 TI - [Alteration of lymphocyte surface markers in patients with hemophilia]. PMID- 6241946 TI - [T cell function in psoriasis--analysis of T cell suppressor function in psoriasis]. PMID- 6241947 TI - Electrophoretic variants of blood proteins in Japanese. II. Phosphoglucomutase-1 (PGM1). PMID- 6241948 TI - [Occupational cervicobrachial disorder (OCD) of nursery school teachers based on subjective symptoms related to OCD]. AB - To clarify the association of occupational cervicobrachial disorder (OCD), with labor conditions, and personal situation, a questionnaire study was conducted among nursery school teachers. The questionnaire was composed of subjective symptoms related to OCD (neck, shoulder, back and arm stiffness/pain), labor conditions, and whether or not the teacher had a child of her own under the age of two. Data of 793 subjects were analyzed. The results were as follows: The mean age and working period of 793 subjects were 27.6 (+/- 4.9) and 5.5 (+/- 3.2) years, respectively. Of them, 38.5% complained of right shoulder stiffness every day during the prior month, 26.5% neck stiffness, 18.8% arm stiffness, 9.6% back pain, 7.8% shoulder pain and 3.9% arm pain. The complaint rates on the left side were similar to those on the right side. The complaint rates of these subjective symptoms increased with the duration of the working period. The complaint rates of shoulder, neck and arm stiffness increased earlier than those of back stiffness, shoulder or arm pain. The complaint rates of these symptoms were highest among teachers in charge of children less than one-year-old and those in charge of four-year olds. Teachers in charge of three-year-old children had the lowest complaint rates. Subjects complaining of neck, shoulder and arm stiffness on every day worked under less favorable conditions than those without such complaints. When subjects having no children of their own under the age of two were matched in their ages and length of work history with those who have such children, the complaint rates of the two groups did not differ statistically for any of the subjective symptoms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 6241949 TI - [Studies on health hazards among cooks providing school lunch service. Report 1. The influence of working conditions in central and school kitchens prevalence of health hazards]. AB - Since the School Lunch Law was enacted in 1954, the school lunch program in Japan has seen rapid development, mainly in compulsory schools. Eighty-four percent of all pupils in compulsory schools are fed lunch, and nearly half of the meals are provided by the central kitchen system. There has been much criticism of the central kitchen system concerning the quality of the meals. Recently, it has been demonstrated that many cooks suffer from musculo-skeletal symptoms in their necks, shoulders, arms and lower backs. This paper discusses the relationship between the cooking work load and health hazards by comparing the tasks of cooks in the central kitchen system with those of cooks in individual school kitchens. All the female cooks in one prefecture were queried by a mail survey method. The respondents totalled 1,428 (response rate 68%). Of this number, 186 work in 15 central kitchens (group C) and the other 1,242 work in 401 school kitchens (group S). In addition physical examinations were carried out on cooks who registered serious complaints in the questionnaires and on those who wanted to undergo the examination. The results are as follows: The work load in the central kitchens is greater than that in the school kitchens. Both groups C and S complained of cervicobrachial symptoms and low-back pain as frequently as other workers already reported to be in a high risk of these hazards. Group C suffer from these hazards more frequently and seriously than group S. Group C assigned "carrying heavy objects" as a cause of low-back pain and cervicobrachial symptoms more frequently than group S. This was related to the difference in numbers of meals served by groups C and S. As a result of the physical examination, serious cases of cervicobrachial disorders and/or low-back pain were found more frequently among cooks who had serious complaints than among other examinees. It was concluded that these results demonstrated a positive relationship between the cooking work load and the development of health hazards. Therefore, if we wish to protect cooks from these hazards, it is not advisable to maintain the current central kitchen system. PMID- 6241950 TI - [Studies on health hazards among cooks providing school lunch service. Report 2. An analysis of factors associated with the development of health hazards]. AB - The previous report revealed that the musculoskeletal symptoms of cooks are related to their working conditions, but the cause and effect relationship was not clarified. In the present report, the relationship between some causative factors and the health hazards is analyzed epidemiologically. The subjects were chosen from the cooks mentioned in the previous report. The results are as follows: A clear relationship was not observed between age and health hazards. A dose-response relationship was observed between the cumulative duration of cooking work and the subjective symptoms. An antecedent-consequent relationship was also shown between the cooking work and the health hazards. Another dose response relationship was observed between the amount of cooking work and the subjective symptoms. The frequency of "carrying heavy objects" assigned as a cause of development of the hazards, especially of low-back pain, increased in accordance with the number of meals served in each kitchen. It was observed that the improvement of cooking equipment enabled the incidence of symptoms to decline, but the elevation of working speed due to mechanization could still be hazardous. As a result of the physical examination, a similarity was observed between the cooking work and the clinical findings in comparison with ticket vending machine operators. It is concluded that these results demonstrate a cause and effect relationship between cooking work and the development of health hazards. PMID- 6241951 TI - Effects of elevated-hematocrit levels on pulmonary circulation in conscious sheep. AB - We investigated the effects of stepwise hematocrit (Ht) increase on pulmonary circulation in conscious sheep (n = 7). The Ht was increased by an isovolumic exchange transfusion of blood with centrifuged red cells. By increasing the Ht values, both systemic (PSA) and pulmonary artery pressures (PPA) were increased, with the degree of PPA increment greater than that of PSA. Cardiac output (CO) was slightly decreased by increasing the Ht. Also, A-V difference values of blood oxygen tension were reduced with elevation of the Ht values. The ratio of the right ventricular work rate (RVW) to the left one (LVW), RVW/LVW, was shown to increase remarkably with increased Ht. This increase was considered to be supporting evidence for the right ventricular hypertrophy in high altitude acclimatization. A strong positive correlation was observed between Ht and blood viscosity. It was thus confirmed that Ht effect was greater in pulmonary circulation than in systemic circulation. PMID- 6241952 TI - Detection of terminal complement components in experimental immune glomerular injury. AB - Complement mediates glomerulonephritis by inflammatory cell-dependent and non inflammatory cell-independent effects on glomerular permeability. The latter may involve terminal components of the complement system. We examined several models of immunologic renal injury in the rat by immunofluorescence (IF) for terminal complement components C5, C6, C7, and C8 in glomeruli using antisera to human C5 8, which cross-react with the analogous rat complement components. Rats with the heterologous and autologous phases of passive Heymann nephritis (PHN) had proteinuria and 1 to 2+ capillary wall deposits of heterologous or rat IgG, rat C3, and C5-8. Complement depletion with cobra venom factor (CVF) significantly decreased proteinuria in both models and prevented deposition of all complement components. Rats with active Heymann nephritis had similar deposits of rat IgG and C5-8. Rats with anti-GBM nephritis and aminonucleoside nephrosis had severe proteinuria which was not affected by CVF treatment and deposits of C5-8 were absent. The presence of terminal complement components in immune deposits in experimental glomerular disease correlates with a functional role for complement in mediating glomerular injury. These data support the hypothesis that the terminal complement pathway may be a major mediator of some types of immune glomerular injury. PMID- 6241953 TI - Folk medicine in Tonga. A study of the use of herbal medicines for obstetric and gynaecological conditions and disorders. AB - We report on a study of the role of traditional medicinal practices in two communities in the South Pacific Kingdom of Tonga, with particular emphasis on obstetric and gynaecological complaints of women and the traditional practitioners consulted by them. Data on the nature and frequency of obstetric and gynaecological complaints, patterns of consultations and preferences for the type of practitioner, Western or traditional, were collected from housewives. The nature, range and extent of expertise possessed by traditional practitioners were also assessed. The results indicate that reliance on traditional medicine is rapidly declining in favour of Western medicine. This seems to be due to urbanisation, increased acceptance of Western values and a lack of availability of traditional practitioners in sufficient numbers. However, self-administration of herbal remedies was still common, especially in rural areas, and might even be on the increase. The practitioners treated a variety of obstetric and gynaecological complaints using 60 plant species which were collected and identified. PMID- 6241954 TI - Schistosomal glomerular disease (a review). AB - In this review paper schistosomal glomerulopathy is defined as an immune-complex disease. The disease appears in 12-15 per cent of the individuals with hepatosplenic schistosomiasis. Portal hypertension with collateral circulation helps the by pass of the hepatic clearance process and the parasite antigens can bind to antibodies in the circulation and be trapped in the renal glomerulus. Chronic membranous-proliferative glomerulonephritis is the most common lesion present and the nephrotic syndrome is the usual form of clinical presentation. The disease can be experimentally produced, and schistosomal antigens and antibodies, as well as complement, can be demonstrated in the glomerular lesions. Specific treatment of schistosomiasis does not seem to alter the clinical course of schistosomal nephropathy. PMID- 6241955 TI - The pathophysiology of movement disorders. AB - This review concentrated on the more recent findings of investigations into the functional anatomy and pathophysiology of movement disorders. Attempts were made to provide explanations for rigidity, bradykinesia, and tremor. What little is known of the pathophysiology of chorea, tics, and dystonia is discussed. Greater information is available to allow pathophysiologic classification of different types of myoclonus. PMID- 6241956 TI - Molecular genetics, basal ganglia disorders, and the clinical neurologist. AB - The emphasis of this article is on gene mapping, clinical neurogenetics, genetic factors in common disease, and classification of the hereditary disorders of the basal ganglia. This was influenced by the recent assignment for the Huntington's disease gene to chromosomes 4 by Gusella, Wexler, and Conneally and the fact that several comprehensive reviews of the genetics of basal ganglial disease have recently been published. PMID- 6241957 TI - [Obstetrical and perinatal risks in elderly pregnant women]. PMID- 6241958 TI - The helminths of various antelope species from Natal. AB - Helminth parasites were collected from 2 bushbuck, Tragelaphus scriptus, 2 red duiker, Cephalophus natalensis, 1 oribi, Ourebia ourebi, and 4 reedbuck, Redunca arundinum, that died or were culled in various parts of Natal. One trematode genus, 1 cestode genus and 12 nematode species were recovered. Haemonchus contortus. Ostertagia harrisi, Trichostrongylus capricola, Trichostrongylus vitrinus, Cooperia rotundispiculum and Setaria scalprum are new parasite records for the red duiker. Trichostrongylus colubriformis is a new parasite record for the oribi and Longistrongylus schrenki, Trichostrongylus falculatus, Trichostrongylus colubriformis and Dictyocaulus viviparus are recorded from the reedbuck for the first time. An unidentified paramphistome was also recovered from the reedbuck. PMID- 6241959 TI - [Mechanisms of demyelination--acute and chronic relapsing experimental allergic encephalomyelitis]. PMID- 6241960 TI - [Mucopolysaccharidoses and disorders of glycoprotein metabolism]. PMID- 6241961 TI - [Huntington's disease--review on neuroscientific approaches]. PMID- 6241962 TI - [Fibronectin in cell, developmental, and neural biology]. PMID- 6241963 TI - [Therapeutic trial of medroxyprogesterone acetate in severe fibrocystic breast disease]. PMID- 6241964 TI - [Epidemiology of backache: results of education]. PMID- 6241965 TI - [Studies of the kinetics of bone concentration of mdp-tc 99m in Paget's disease and various treatment methods]. AB - We did 27 bone scintiscans in 20 patients, 15 of whom had Paget's disease. Early variations of isotopic activity were analyzed in the pagetic bone, and in normal bone and muscle tissue using 3 parameters: A1 or the period of maximum activity obtained when the isotope was first injected into the circulation, A2 or the isotopic activity at 30 minutes, and P or slope of the curve in the change of activity between 15 and 30 minutes. These scintigraphic parameters, which seem to reflect the importance of the vascular phase (parameter A1) and of the metabolic activity of the bone (parameter A2/A1 and P) proved to be a good guide in following the course of Paget's disease. In 6 patients with Paget's disease who were treated with calcitonin (5 cases) or by etidronate disodium (1 case), we compared the changes in these isotopic parameters with the clinical and laboratory findings before and after treatment. We were able to note a good correlation between the clinical course of the illness and the scintiscans in most cases. PMID- 6241966 TI - [Antibacterial activity of norfloxacin and pipemidic acid in a randomized double blind study]. PMID- 6241967 TI - Arsenic and old taxa: subspeciation and drug sensitivity in Trypanosoma brucei. AB - Resistance to the trypanocidal drugs atoxyl and tryparsamide was traditionally considered to be a diagnostic feature of rhodesian sleeping sickness and, consequently, of Trypanosoma rhodesiense. In examining the tryparsamide sensitivity of 13 isoenzymically defined stocks of the subgenus Trypanozoon, typical West African stocks showed no greater drug sensitivity than did those of East and Central Africa. The greatest resistance to tryparsamide was shown by two stocks isolated in the Ivory Coast. There was no evidence of strain differences in drug sensitivity to melarsoprol (Mel B) among 26 tested populations; none the less, differential melarsoprol sensitivity was evident in clones from a single mixed population. By contrast, isoenzymically defined West African stocks appeared to be less sensitive to pentamidine and diminazene aceturate (Berenil) than were typical East African stocks. Drug sensitivity was measured in a novel in vivo test designed to minimize the influence of host-parasite interactions, in particular trypanosome penetration of drug-inaccessible sites and host-antibody induced remission of parasitaemia. Drug effect was expressed as the DS0.1, the dose required to suppress parasitaemia to 0.1% of that in untreated control mice. PMID- 6241968 TI - Noninvasive and invasive blood flowmetry in hemodialyzed patients with high blood flow fistulas. PMID- 6241969 TI - Repeatable access blood flow (ABF) measurement. PMID- 6241970 TI - Effects of a tetrafluoroethylene glow discharge on patency of small diameter dacron vascular grafts. PMID- 6241971 TI - Exercise-induced ventricular dysfunction: reversible by hemodialysis. PMID- 6241972 TI - Methods available for plasma component removal. PMID- 6241973 TI - Percutaneous transluminal coronary angioplasty: seven years' experience. PMID- 6241974 TI - [Exercise test with thallium 201 scintigraphy for the early evaluation of coronary angioplasty in one-vessel disease]. PMID- 6241975 TI - Chronic active hepatitis (CAH). The diagnostic and prognostic value of laparoscopy. PMID- 6241976 TI - Characteristics of lymphocyte and macrophage reactivity in otitis media with effusion. AB - On the basis of our observations and previously published data, it is proposed that in at least certain forms of chronic otitis media with effusion there is a relative predominance of macrophage--monocyte cells which are actively immunosuppressive for the proliferative response to mitogens and specific antigens, as well as for the synthesis of specific immunoglobulins. Such immunological hypo-responsiveness may be related to the pathogenesis of chronic otitis media with such effusions. PMID- 6241977 TI - The role of microorganisms in experimental eustachian tube obstruction. PMID- 6241978 TI - Immunological and biochemical properties of tonsillar lymphocytes. AB - No significant differences were found between hyperplastic tonsillitis and recurrent tonsillitis in the intensity of cell-mediated immune response of tonsillar T cells, the ratio of T cell subsets, the ratio of Tac-positive cells, and the stimulation index determined after incubation in the presence of TCGF alone. However, the proportion of the cells in phase S+G2+M, the ratio of OKT9 positive cells to total tonsillar lymphocytes, and the amount of polyamines (especially putrescine) were greater in hypertrophied tonsils than in the tonsils with recurrent tonsillitis. Some characteristics of recurrent tonsillitis are discussed from these differences. Comparison of tonsillar lymphocytes from children vs. adults produced similar results. The proportion of cells in phase S+G2+M, the ratio of OKT9, and the amount of polyamines were greater in tonsils of children. In addition, differences in the function of tonsillar and peripheral lymphocytes from the patient are also discussed. PMID- 6241979 TI - The adolescent back. A field survey of 370 Finnish schoolchildren. AB - In this study, dealing with the early diagnosis and prevention of back pains, adolescent postural faults especially in the sagittal plane were examined with a standardized physical examination technique suitable for use in schools; the strength and flexibility of muscles affecting the back were investigated; neck and/or back symptoms were screened; and the association of background factors and the findings of the physical examination with symptoms was evaluated. The material consisted of a total of 370 11, 13, 15 and 17-year-old comprehensive and senior secondary school pupils from a small suburban municipality, selected by random sampling. The subjects were quite evenly distributed in terms of different age and sex groups. The physical examination of the back, with evaluation of symptoms, took place in the autumn of 1981 in the premises of school health care, and 58 of the examined subjects were referred on the basis of symptoms and/or findings to an X-ray examination of the thoracic and/or lumbar spine. The X-rays were taken in the spring of 1982. 1 Back pain history. Relation between present neck and/or back symptoms, background variables and findings in physical examination. 7.6% of the subjects reported previous neck and/or back symptoms that had interfered with their school work or leisure activities. Present, mainly mild neck and/or back symptoms were reported by 19.7%. Girls reported symptoms more often than boys (p less than 0.05), and the occurrence of symptoms increased with age (p less than 0.001). Roughly one third of the subjects had frequent symptoms. Pains were most often localized in the low back (p less than 0.001) and were most frequently associated with sitting or physical activities. Most subjects who had suffered from previous symptoms also reported symptoms at the time of the study. These more chronically symptomatic subjects accounted for 6.2% of the total material. 2.9% of siblings under 11 years, 8.0% of siblings 11-17 years, and 13.7% of siblings over 17 years of age had at some time prior to the study complained of recurrent neck and/or back symptoms. Of mothers, 19.0% and of fathers, 15.4% reported neck and/or back symptoms that were continual and/or reduced working ability. The mother (p less than 0.01) and/or the father (p less than 0.05) of a subject reporting frequent symptoms, also reported neck and/or back symptoms.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 6241980 TI - The effect of cell size and capillary spacing on myocardial oxygen supply. AB - Recently, we collected basic morphometric data from normal and hypertrophic rat hearts: median and mean values of the cell diameter and of the intercapillary distance as well as their variabilities. In the present communication we used these data, first for analysis of the effect of the heterogeneity of capillary spacing on the myocardial tissue PO2. Comparison of tissue PO2 histograms calculated for a situation in which the capillaries are evenly distributed as in the Krogh model, with a situation based on the same capillary but variable intercapillary distances clearly demonstrates the importance of heterogeneity of the capillary spacing as a separate oxygen determinant. This is even more important in the hypertrophic hearts which are characterized by longer and more variable intercapillary distances. In the second part, we compared the classical Krogh model with a model of concentric diffusion in which the oxygen consumption was either uniform or divided into two zones of distinctive rates. Oxygen profiles calculated for the Krogh model with excentric diffusion were similar to those derived for the two models of concentric diffusion. PMID- 6241981 TI - Amino acid composition and characteristic indices of bovine seminal plasma in case of infection of semen by mycoplasmas. PMID- 6241982 TI - Cross-reactions between Mycobacterium avium and Mycobacterium paratuberculosis strains in complement fixation and gel precipitation tests. PMID- 6241983 TI - Pathological studies in chicken embryos and day-old chicks experimentally infected with Salmonella typhimurium and Staphylococcus aureus. PMID- 6241984 TI - Rapid analytical method for the quantitative determination of trichothecene toxins in food and feeds. PMID- 6241985 TI - Occurrence of mycotoxins in feeds, animal organs and secretions. PMID- 6241986 TI - Comparison of the structure of Sarcocystis cuniculi of the European rabbit (Oryctolagus cuniculus) and Sarcocystis leporum of the cottontail rabbit (Sylvilagus floridanus) by light and electron microscopy. PMID- 6241987 TI - In vitro cultivation of Trypanoplasma strains isolated from pike and leech (preliminary report). PMID- 6241988 TI - Reverse radioimmunoassay for separation of iodothyronines (research notes). PMID- 6241989 TI - Substrate and inhibitor specificity of a transient, soluble proteolytic activity from sheep rumen. PMID- 6241990 TI - An outbreak of Morel's disease (a contagious sheep disease accompanied by abscess formation) in Hungary. PMID- 6241991 TI - Occurrence of trypsin inhibitors in colostrum, meconium, and faeces of different species of ungulates and carnivores. PMID- 6241992 TI - Rapid determination of monensin and nigericin in medical premixes and in growth promoting feed preparations. PMID- 6241993 TI - [Donors and receptors of biologically labile methyl groups: characterization with a nicotinamide-trigonelline system]. AB - The problem of transmethylations, the genesis of the labile methyl groups, the chemical structure of a transmethylating active substance are briefly explained and discussed. A methodology to characterize quickly the substances donor and acceptor of methyl groups is here described: it utilizes the ox crystalline lens in the presence of nicotinamide. The methodology is based on the irreversible system nicotinamide-trigonellinamide, by means of the vitamin B1 as catalyst. PMID- 6241994 TI - [Therapy of severe acne and acne rosacea with oral 13-cis-retinoic acid (Isotretinoin)]. AB - Forty patients suffering of different forms of acne (papulo-pustular, nodulo cystic, conglobata, rosacea), all in severe conditions and non-responding to other treatments, have been administered 13-cis-retinoic acid p.o. The treatment resulted in a complete and ultimate healing in 31 pts (77.5%) and a marked amelioration in the remaining 9 cases. The initial drug dosage was 40 mg/die (an average of 0.66 mg/kg/die) but it was reduced along the treatment to 2.5 mg/die, a still effective dose. The average treatment duration was 24 weeks (range: 12 to 40). The tolerance was generally excellent, but some adverse effect have been recorded, mainly localized in the skin and mucosa. Increases of total serum cholesterol (66% of the cases) and of triglyceride (72%) level have been observed. This effect was reversible at the end of the treatment. As a conclusion we can confirm that the 13-cis-retinoic acid is the most effective drug for the pharmacotherapy of severe acne. PMID- 6241995 TI - Impaired immune regulation in children and adolescents with hemophilia and thalassemia in Israel. AB - The immune function was assessed in 22 children, adolescents and young adults with asymptomatic hemophilia, and 15 with thalassemia, in Israel. Five patients with hemophilia and two with thalassemia were found to be severely abnormal, having cutaneous anergy, very low T-helper cells, elevated T-suppressor cells, inverted T-helper/suppressor ratio, reduced response to mitogens and antigens, and nonfunctional NK cells. Four of the five hemophilia patients exhibited profound lymphopenia also. Decreased T-helper and mildly elevated T-suppressor cells with inverted T4/T8 ratio were observed in the hemophiliacs as a group. In the severe group, the reduction in T-helpers and T4/T8 ratio was more pronounced. The thalassemics as a group were found to have increased numbers of T-suppressor cells with decreased T-helper cells in those with intact spleen only. Both groups studied were found to have elevated IgG levels and low natural killer (NK) activity and normal response to mitogens. Cutaneous anergy was found to be a reliable indication for severe T-cell dysfunction and may serve as an early indication of impending AIDS. These results indicate that patients with hemophilia and with heavily hypertransfused thalassemia may be at increased risk of AIDS as they approach adolescence. PMID- 6241996 TI - [Reactive arthritis: an entity or a borderline]. PMID- 6241997 TI - The presence, synthesis and disposition of quinolinic acid in the central nervous system: developmental studies. PMID- 6241998 TI - Immunologic abnormalities among male homosexuals in New York City: changes over time. PMID- 6241999 TI - An acquired immunodeficiency syndrome among Haitians: an update. PMID- 6242000 TI - Pediatric acquired immunodeficiency syndrome. AB - Approximately 40 to 50 infants and children with similar epidemiologic, clinical, and laboratory features of AIDS have been described. The occurrence of significant numbers of patients with PAIDS in geographic areas that are associated with similar risk factors and clinical features of AIDS suggests a common cause. Immunologic evaluation reveals hypergammaglobulinemia, decreased or absent antibody responses after immunization, normal to decreased T-cell numbers, decreased helper/suppressor cell ratios, and abnormal results of functional studies of T-cells. None of the patients described has the clinical or laboratory features of well-established congenital immunodeficiency disorders. No consistent viral agent has been documented except for antibody to ARV and HTLV III. The frequent finding of T-cell abnormalities in the mothers of infants with PAIDS is in contrast to the absence of such abnormalities in the mothers of infants with congenital immunodeficiency disorders. Future studies in PAIDS should be directed toward uncovering the etiology and risk factors as well as determining the response to treatment with various methods of immunologic reconstitution. PMID- 6242001 TI - Immunologic studies of the acquired immune deficiency syndrome: relationship of immunodeficiency to extent of disease. AB - Immunologic and conventional laboratory studies were done in 135 previously untreated subjects including 28 (20.7%) symptom-free homosexuals and 74 (54.8%) with ARC and 33 (24.5%) with AIDS. More than half of all patients had abnormal percentages of lymphocytes, percentages of T3+ cells, percentage and absolute number of T4+ cells, percentage of T8+ cells, T4/T8 ratio, monocyte adherence, and serum thymosin alpha 1. Most immune variables worsened with progressive disease. Low lymphocyte 5'nucleotidase increased suppressor cell activity, and impaired IL-2 and alpha interferon production and response suggest diminished mature and increased immature peripheral blood and tissue T cells. These findings suggest approaches to staging, prognostication, and treatment for AIDS. PMID- 6242003 TI - Autoantibodies to T cells in adult and pediatric AIDS. PMID- 6242002 TI - AIDS in hemophilia. PMID- 6242004 TI - Immunological studies in patients with acquired immune deficiency syndrome. PMID- 6242005 TI - Soluble factors inhibitory for T-cell-dependent immune responses in patients with the acquired immune deficiency syndrome and its prodromes. AB - Supernatants from PBMC obtained from certain patients with AIDS or its prodrome were capable of depressing pokeweed mitogen-driven immunoglobulin production and the proliferative response of T cells to specific antigen. These soluble suppressor factors (SSF) were present in uniquely high concentrations, and were the product of an interaction of T lymphocytes with adherent cells. T-cell independent functions were not modified by soluble suppressor factors. Restoration of immunoglobulin synthesis in SSF-treated cultures was realized by addition of reducing agents such as 2-mercaptoethanol, suggesting inhibitory mechanisms possibly related to that of Con A-induced soluble immune response suppression, and perhaps offering clues to clinically applicable substances capable of modifying such responses. A relationship between SSF-AIDS and a human retrovirus LAV/HTLV III, linked etiologically to AIDS and its prodromes, is suggested by studies of SSF-like substances released by human T-T cell hybridomas derived from LAV+ patients. PMID- 6242006 TI - Comprehensive immune evaluation of seventy-eight hemophiliacs. PMID- 6242007 TI - Immune derangements in asymptomatic male homosexuals in Israel: a pre-AIDS condition? AB - We have described several immune derangements found in a clinically asymptomatic group of 117 male homosexuals (MHS) in Israel. These consisted of a marked decrease in TH and TS cells, decreased NK and allogeneic response, and increased levels of acid labile alpha-interferon and circulating immune complexes (CIC). Most of these alterations were found in approximately 40% of the subjects, with no simple correlation between them. Since Israel is a low incidence area for AIDS and related syndromes, it is suggested that this situation reflects a common situation among asymptomatic MHS in general, although the reasons for these impairments are not clear. This situation may therefore explain susceptibility of the male homosexual for developing AIDS, given the appropriate circumstances, environment, and genetic background. PMID- 6242008 TI - A longitudinal study of cellular immunity in male homosexuals in London. PMID- 6242009 TI - T-cell ratios: sperm and asialo GM1 antibody levels in New York City prostitutes. PMID- 6242010 TI - Characteristics of a seminal plasma inhibitor of sperm motility. PMID- 6242011 TI - Scanning transmission electron microscopy of dynein arms. PMID- 6242012 TI - [Arteriovenous fistula formation: report of 72 cases]. PMID- 6242013 TI - Reversal of impaired renal function in rats with streptozotocin-induced diabetes by transplantation of isolated pancreatic islets: failure in preventing the progress of glomerulosclerosis. PMID- 6242014 TI - Cells involved in autologous rosette formation in mice. I. Two different subpopulations of thymocytes regulating autologous rosette formation. AB - In the studies on mouse thymocyte subpopulations--non-glass-adherent (NAL) cortisone-sensitive (HCS), and glass-adherent (GAL) cortisone-resistant (HCR) thymocytes the existence of precursors for helper and suppressor cells of the autologous rosette formation was demonstrated. A proline-rich polypeptide (PRP), an immunoregulator induced differentiation of helper and suppressor cells from NAL and GAL cells, respectively. These cells elevate or inhibit formation of autologous rosette by thymocyte subpopulations in vitro. Helper activity was abolished by treatment with monoclonal anti-Lyt 1,1 antibodies and suppressor activity was totally inhibited after treatment with monoclonal anti-Lyt 2,1 antibodies. PMID- 6242015 TI - [Studies of phosphorylation in rat mast cells (fourth report)--isolation of calcium-activated, phosphatidylserine and diacylglycerol-dependent protein kinase]. PMID- 6242016 TI - Allergic contact dermatitis to dimer acid product--a flexibilizing epoxy resin hardener. PMID- 6242017 TI - [Effects of a treatment with a thymus extract (thymostimulin) in acute viral hepatitis B in drug-dependent patients]. AB - The authors carried out a controlled therapeutic trial with Thymostimulin in 43 drug addicts affected by acute type B anti-Delta negative viral hepatitis. Both clinical and immunological picture seem to improve following treatment. PMID- 6242018 TI - [Left ventricular hypertrophy in older hypertensives: electro- and echocardiographic correlations]. PMID- 6242019 TI - [Tetralogy of Fallot associated with atrioventricular septal defect: clinical experience in 11 patients]. PMID- 6242020 TI - [Glycolytic metabolism in Tawa sarcoma cells: regulation of phosphofructokinase activity by its substrate]. PMID- 6242021 TI - [Experimentally induced diabetes in spontaneously hypertensive rats (SHR) (I)]. PMID- 6242022 TI - Experience with an LHRH analogue in the management of relapsed progressive prostatic cancer. AB - Seventeen patients with advanced progressive prostatic cancer who had relapsed or failed to respond to conventional endocrine therapy with oestrogens, orchiectomy or antiandrogens were treated with the LHRH analogue, ICI 118630. No significant objective tumour responses were seen, though 11 of 15 patients who presented with symptomatic metastatic bone pain had rapid short-term pain relief. The lack of objective clinical response seen in this study indicates no justification for the use of LHRH analogues in this group of patients. Though a significant subjective response was seen there was no added advantage over regular analgesics. PMID- 6242023 TI - Tongue movements--brainstem mechanisms and clinical postulates. AB - Specific excitatory and inhibitory influences on protrusive (P) and retrusive motoneurons in the hypoglossal nucleus of cat have been documented. Stimuli delivered to peripheral branches of the auriculotemporal nerve which innervate the temporomandibular joint activate both genioglossus (GG) single units and synaptically-evoked responses in P motoneurons. Similarly, stimuli delivered to the glossopharyngeal (IX) and superior laryngeal nerves activate P motoneurons. Any one of these three stimuli may contribute to the various responses in which the GG muscle is known to participate. In contrast, stimuli applied to the tongue itself (lingual and IX nerves) result in a retrusive tongue movement. These brainstem mechanisms suggest specific therapy regimens for the treatment of skeletal open-bite malocclusions where resting tongue posture appears to be a primary etiological factor. PMID- 6242024 TI - A study of jaw reflexes of the awake cat during mastication and locomotion. AB - This paper reports on experiments on the jaw opening reflex carried out while awake unrestrained cats were eating or walking on a treadmill. It is shown that the jaw opening reflex response to low intensity stimulation diminished in all phases of the masticatory cycle. The response to higher threshold afferents, however, is phase modulated so that the largest responses occur during the jaw closing phase. This is in accord with the need for increased protection of the soft tissues in this phase of the movement. In contrast, the digastric reflex amplitude does not change when the cat passes from quiet standing to walking on the treadmill. Evidence is presented that the electromyographic activity of the jaw closing muscles increases during upwards movement of the head during walking and decreases as the head falls. These data support the hypothesis that the myotatic reflex in the elevator muscles plays a role in stabilizing the mandible during locomotion. PMID- 6242025 TI - Interaction of periodontal and jaw elevator spindle afferents in the cerebellum- sensory calibration. AB - Electrical stimulation of low threshold, fast afferents in the inferior alveolar nerve produce very short latency synaptic field potentials in the cerebellar cortex anterior lobe typical of mossy fibre inputs. The afferents concerned are from periodontal receptors, some of which project directly without relay. Muscle afferents do not show this direct projection. The functional significance of this arrangement is discussed, bearing in mind the parallel with the direct projection of some first order vestibular afferents. It is suggested that the specialisation seen may be the basis for sensory calibration of spindle inputs by means of periodontal afferents. PMID- 6242026 TI - Brainstem mechanisms for feeding in birds: interaction or plasticity. A functional-anatomical consideration of the pathways. AB - Starting from a functional-anatomical analysis of the feeding apparatus of a bird, some expectations are formulated regarding the organization of the neuronal systems controlling the activity of this feeding apparatus. The organization of the premotor-motor system of the jaw muscles, of the exteroceptive system conveying tactile sense from tongue and beak to the brain and of the proprioceptive system of the jaw muscles is discussed. An attempt is made to relate specific structural features of these systems to their function in the control of the different feeding patterns of birds. PMID- 6242027 TI - [Transluminal coronary angioplasty (apropos of 135 cases)]. PMID- 6242028 TI - [Neurochemistry of lipids in the nervous system, fatty acids in particular. Neurotoxicologic prospects]. AB - Each membrane in the brain is constituted of peculiar fatty acids which are related to its biological function. The nervous system is a highly lipid-rich tissue, essentially represented by fatty acids. The brain is able to synthetize both saturated and mono-unsaturated fatty acids independently of the chain length. The nature, the localization, the biochemical mechanisms and the regulation process of synthesis have been studied at the cellular and subcellular level. The fate of fatty acids, particularly their function of precursor in the synthesis of lipids, has been analysed. However the fact all the fatty acids are not synthetized in situ, strongly suggests that they have a seric origin. The seric fatty acids are eventually synthetized in the liver or can originate from diet. Malnutrition (pre- or post-natal) causes serious abnormalities in the brain fatty acids composition. The alimentary origin of poly-unsaturated fatty acids being absolute, the relative quantities of fatty acids of the w3 and w6 series must be precisely determined. The poly-unsaturated fatty acids control the membrane fluidity, and therefore their metabolic activities. PMID- 6242029 TI - [Value of the perifusion of fragments of rat thyroid for the dynamic study of thyroid secretion under TSH and theophylline]. AB - With the technique of rat thyroid fragment perifusion the kinetics of T4 response to various stimuli can be studied with precision. The response is rapid and brief with theophylline and TSH, which activate membrane adenylcyclase; with the optimal concentrations, however, it is prolonged because only these concentrations can induce the secretion of a more slowly releasable pool of T4. PMID- 6242030 TI - [Importance of the excretion of triiodothyronine (T3) in normal infants and children]. AB - Serum concentrations of thyroxine (T4) and triiodothyronine (T3) are higher in normal neonates and children than in adults, having a thyroxine to triiodothyronine ratio close to 50. T3 excretion is almost as high as that of T4 (T4 to T3 ratio from 0.6 to 0.8 in children). This amount of excreted T3 represents a loss of about 1/10 of the theoretical daily production rate of the hormone. PMID- 6242032 TI - [Origin of the secondary peristalsis of the esophagus in sheep]. AB - Manometric and electromyographic methods were used for investigating oesophageal motor activity in conscious sheep. A contraction wave, the so-called "secondary peristalsis", was readily evoked by means of the fast inflation of a rubber balloon distending the oesophagus. This peristaltic wave travels onto the cardia at the same speed as the primary deglutitive peristalsis (28 m X sec-1, approximately). In that particular species, whose oesophageal muscular coat is all along entirely made of striated fibers, secondary peristalsis is always initiated at the origin of the cervical oesophagus, whatever the site, cervical or thoracic, of the distension. PMID- 6242031 TI - [Natriuria during immersion of brief duration]. AB - During immersion in sitting position to the neck of 10 normal adult males, natriuria is significantly increased even after pretreatment with captopril (2 mg X kg-1, p.o.). Inhibition of the renin-angiotensin-aldosterone cascade does not completely block the mechanisms causing natriuria during immersion. PMID- 6242033 TI - [Blood serotonin and histamine in sheep with endemic scrapie: initial results]. AB - The whole blood histamine levels of sheep without clinical scrapie but living in infected farms, control, and scrapie infected sheep are not significantly different. By contrast whole blood serotonin is decreased both in sheep living in infected farms and in scrapie-infected sheep as compared to controls. Thrombopenia may account for the hyposerotoninemia of sheep living in infected farms except those genetically linked to scrapie-infected sheep for which, as for scrapie-infected sheep, platelet serotonin appears also to be diminished. Whole blood serotonin determination might therefore be useful to detect sheep living in infected farms (these sheep probably play an important role in scrapie infection) and perhaps also humans with high susceptibility to Creutzfeldt-Jakob disease. PMID- 6242034 TI - [Seasonal cycles of plasma testosterone and cortisol in the wild rabbit (Oryctolagus cuniculus algirus Loche) of Zembra Island, studied in its natural biotope and in captivity]. AB - Annual variations in plasma testosterone and cortisol levels were determined in male wild rabbits caught monthly in their natural biotope (Zembra island). For comparison, a group of warrens was hold in semi-captivity close to Tunis. In both conditions plasma testosterone concentrations were low from January to September and peak values were observed in October. Captive warrens exhibited a clear cut annual rhythm in plasma cortisol levels also and ether stress resulted in a very large increase of cortisolemia. In rabbits caught in ther habitat however, cortisol concentrations were always extremely high throughout the year, probably due to stressing conditions. Interestingly, wild rabbits of Zembra island appear to subsist from a very remote past without any contact with other strains. As to Zembra, it is a hardly get-at-able, uninhabited island which is a part of a strictly protected natural reserve and constitutes a fairly useful and valuable ecosystem. PMID- 6242035 TI - [Effect of an acidic sulfated polysaccharide on whole blood coagulability. In vivo study in rats]. AB - Armatan, an acid sulphated polysaccharide isolated from a red marine seaweed Asparagopsis armata (Harv.), increases the coagulation time of the rat plasma in vivo assays. This property presents, with administration, time and dose, some variations. Among the three ways studied, subcutaneous injection gives more interesting results than the others. At high concentrations (10, 20 and 50 mg/kg), intravenous administration induces plasma and organic (liver-spleen) diseases. PMID- 6242036 TI - [Demonstration of hormonal actions on Escherichia coli K 12 by potentiometry in the presence of lipoic acid; correlation with measurements of microbial growth and glucose consumption]. AB - The action of hormones on Escherichia coli K 12 was followed by potential-time measurements in the presence of lipoic acid (LA), photometric determinations of growth and glucose titrations. Bovine growth hormone (5 to 60 IU/1) increased O2 consumption. The (10 IU/1) insulin-facilitated transport of LA was stimulated by glucose. Adrenaline (0.5 to 15 mg/l) increased more glucose and O2 consumption than growth. PMID- 6242037 TI - [Gynecologic celioscopy. Anesthesia technic and prevention of complications]. PMID- 6242038 TI - [Complications of spinal anesthesia]. PMID- 6242039 TI - [General anesthesia and Huntington chorea]. PMID- 6242040 TI - [Prevention of occupational diseases]. PMID- 6242041 TI - [Tetany crisis in the dental office: what to do?]. PMID- 6242042 TI - [Circumstances of development of pain syndrome in patients with spondylolisthesis and spondylolysis]. PMID- 6242043 TI - [Economic aspects of hand injuries in municipal workers in Lodz]. PMID- 6242044 TI - The long wire technique--a new technique for steerable balloon catheter dilatation of coronary artery stenoses. AB - A new technique for steerable balloon dilatation is described. In contrast to the usual procedure the stenosis is first crossed by a long wire only. To minimize injury of the vessel wall the wire is equipped with a thickened ball-shaped tip. After the stenosis has been crossed and the wire tip has been advanced far enough, the balloon catheter is inserted over the long wire. If necessary, the balloon catheter can be removed and another one can be inserted without repeat crossing. If an occlusion is caused by the process of dilatation a perfusion catheter can be advanced distal to the occlusion. Perfusion can be performed by help of a simple syringe-tap system because the cross sectional area of this catheter is much larger than a single lumen of the double lumen balloon catheter. This procedure even allows the dilatation of branching stenoses through the same guiding catheter whereas for the usually performed 'kissing balloon' technique two guiding catheters are required. Preliminary experience with 80 patients has shown that crossing of stenoses is facilitated by the new technique because steering of the guide wire and display by contrast medium injections are unhindered. If required, the balloon catheter can be changed for another one without difficulty. In case of occlusion, the lesion can be crossed again without any risk and repeat dilatation or coronary perfusion can be performed. PMID- 6242045 TI - Electro-vectorcardiographic features of double-chambered right ventricle. AB - Twelve patients with double-chambered right ventricles were investigated to determine the significance of the electrocardiogram and vectorcardiogram in the evaluation of this condition. Two subgroups of individuals having various forms of obstruction to right ventricular outflow with and without intracardiac shunting were utilized as controls. The electrocardiogram of patients with double chambered right ventricle had a characteristic appearance identifiable as a right ventricular hypertrophy pattern seen best in the extreme right precordial leads V4R-V3R with tendency to normalization of pattern in V1 which contrasted with the pattern in both control subgroups. The vectorcardiogram in all 8 cases of double chambered right ventricle in which this study was performed exhibited homogeneity of loop appearance and direction best identifiable in the horizontal plane by a prominent terminal orientation of the loop rightward and posteriorly. Both control subgroups exhibited heterogeneity of loop conformation, significantly more initial right-anterior force and less right-posterior force than the double chambered right ventricle group. The electro-vectorcardiographic findings with double-chambered right ventricle were predictable for this abnormality and appear to have significant diagnostic importance. PMID- 6242046 TI - Two-dimensional echocardiography and radionuclide angiocardiography in pulmonary hypertension. AB - In precapillary pulmonary hypertension two-dimensional echocardiography documents anatomo-functional alterations of valvular and cavitary structures of the heart in real time. It supplies useful information on ventricular interdependence and on the motion of the interventricular septum. In the same kind of pathology first pass or equilibrium radionuclide angiocardiography has been used for the calculation of the ejection fraction of the right ventricle, both at rest and during exercise, breathing either air or pure oxygen. The Authors think that these two methods are complementary. For this reason they decided to associate them and they report here their preliminary experience. Their first observations seem to show that the association of the two techniques is useful in the study of the dimensions and shape of the two ventricles and for the visualisation of even regional abnormalities in motion of the interventricular septum. PMID- 6242047 TI - Behaviour of epoxide hydrolase, glutathione S-transferase, alcohol dehydrogenase, and aldehyde dehydrogenase, respectively, under the influence of carbon disulfide studies with rats in vivo and in vitro. AB - High concentrations of carbon disulfide in rat liver preparations do not change the activities of glutathione S-transferase, alcohol dehydrogenase, or aldehyde dehydrogenase and exert a slightly augmenting effect (not significant) on the activity of epoxide hydrolase. Carbon disulfide administered orally to rats in a high dose enhances the activity of hepatic epoxide hydrolase slightly (not significant), but has no influence on hepatic glutathione S-transferase in the cytosol and in microsomes. The results obtained in vitro and in vivo permit the assumption that occupational CS2-exposure does not appreciably inhibit the activities of epoxide hydrolase and glutathione S-transferase. The in-vitro findings with alcohol dehydrogenase and aldehyde dehydrogenase support the view held in the literature that the alcohol intolerance observed after occupational CS2-exposure ("Antabuse syndrome"-like reaction) is due to an inhibition of aldehyde dehydrogenase by CS2-metabolites of the thiocarbamate type. PMID- 6242048 TI - [Injectable contraception using depot progestagens]. PMID- 6242049 TI - [Laparoscopy in the puerperium]. PMID- 6242050 TI - [Immunological characterization of unusual plasmacytic tumor cells in a disseminated non-Hodgkin's lymphoma]. AB - Using monoclonal antibodies and heterosera, tumor cells from a disseminated neoplasia were characterized that could not be classified by conventional histology. The large, sometimes multinucleated tumor cells expressed Ia antigens and were positive for immunoglobulins both at the surface and intracellularly (mu, delta, kappa). This tumor was infiltrated by a large number of T cells that comprised about two thirds of the total cell number eluted from the tumor and predominantly were of the suppressor/cytotoxic phenotype. This tumor can be defined as a lymphoma of the B cell lineage with an unusual differentiation exhibiting both Ia antigens and surface immunoglobulins in addition to plasmacytoid markers. PMID- 6242051 TI - Role of 5-HT on increased permeability of blood-brain barrier under heat stress. AB - Exposure of young rats (9-10 wks) to chronic summer heat (36 degrees C) or acute heat (38 degrees C 4hr) increased the BBB permeability to Evans blue albumin complex (MW 68,000) and 131I-sodium (MW 154) in different brain regions which correlated well with the increased level of 5-HT in plasma and brain. This increased permeability of BBB and the increased 5-HT level were prevented by pretreatment with p-CPA, indomethacin and diazepam. Cyproheptadine and vinblastine pretreatment however, prevented only the increased permeability of BBB, the plasma and brain 5-HT level continued to remain high. These results indicate a probable role of 5-HT as one of the factors leading to the increased permeability of BBB in young rats following heat stress. PMID- 6242053 TI - Effect of low dose X-irradiation on alloantigen sensitized and unsensitized lymphocytes. PMID- 6242052 TI - The clinical pharmacology of appetite suppressant drugs. AB - One way of gaining a greater understanding of the central mechanisms underlying hunger and the regulation of feeding behaviour in humans is to examine the actions and interactions on hunger and food intake of drugs with known or presumed pharmacological modes of action. To this end we have undertaken a number of studies which fall into three main categories: the mechanisms by which amphetamine anorexia is induced; the possible role of endogenous opioids in feeding; the action of amino acids thought to be involved in the regulation of feeding. In this field the potential for cross-fertilization between basic scientists working with laboratory animals and clinical scientists working with human subjects exists. For example, the clinical pharmacologist has been able to test out hypotheses on human subjects which could only have been developed using laboratory animals. Furthermore, using human subjects it is possible to extend the field of inquiry into an exploration of the subjective dimensions of appetite and hunger. PMID- 6242054 TI - Surgical treatment of renovascular hypertension. PMID- 6242055 TI - Studies on interaction between coagulation factor X and plasmin. PMID- 6242056 TI - [Effect of polishing on the staining of composite resins with various staining agents]. PMID- 6242057 TI - Freeze-fracture of sensory nerve endings in cat muscle spindles. AB - Sensory nerve endings and intrafusal muscle fibres of cat muscle spindles were examined by freeze-fracture electron microscopy. The purpose of the study was to reveal intramembranous specializations that might be associated with the mechanosensory transducer system. Nerve ending membranes were found to contain high concentrations of intramembranous particles (greater than 7500 per micron2) in a range of sizes, but no localized aggregations or non-random arrangements were observed. Nerve ending membranes directly apposed to the surfaces of intrafusal muscle fibres did not appear to be strikingly different from non interface membranes, although some differences in particle concentrations could be detected. The membranes of endings on nuclear bag and nuclear chain muscle fibres differed slightly in the numbers of particles and their distributions to protoplasmic or external fracture faces. It was concluded that intramembranous elements of the mechanoelectric transducer system may be dispersed over the whole surface of a sensory ending, rather than localized to smaller domains. PMID- 6242059 TI - [Immunological studies on renal transplantation. IV. Studies on the mode of action of cyclosporin A]. PMID- 6242058 TI - [Immunological studies on renal transplantation. III. Experimental studies on the immunosuppressive action of cyclosporin A]. PMID- 6242060 TI - [A new analytical method for uroflowmetric studies of men with low voiding volumes due to obstructing diseases of the lower urinary tract]. PMID- 6242061 TI - [Value of radiological measurements of the cardiovascular silhouette in men with hypertension. Radiologico-morphological correlation]. PMID- 6242062 TI - The method and results of rehabilitation of patients with low back pain syndrome. PMID- 6242063 TI - [Characteristics of Propionibacterium strains isolated from patients with acne juvenilis and from healthy persons]. PMID- 6242064 TI - [Role of exercise therapy in the prevention of lumbosacral backache in textile industry workers]. AB - Direct and remote effects of therapeutic exercises on the low-back pain syndrome in cotton-industry workers have been estimated. The treatment was applied to fifty-five patients aged from 30 to 58 (mean age--45) with chronic pain-syndrome, who were submitted to a series of exercises and everyday gymnastics. In the course of treatment the following results were obtained: retreatment of low-back pains, increasing of spines mobility (activity), increasing of abdomen-muscle strength. One-year follow-up demonstrated sickness absenteeism decrease by 66%, as compared to a period of the same duration prior to treatment. PMID- 6242065 TI - [Continuous venous infusion via capillary flowmeters]. PMID- 6242066 TI - Release of disaggregatory prostanoids into circulation by nicotinic alcohol, nicotinic acid and nicotinamide. AB - Nicotinic alcohol, nicotinic acid and nicotinamide caused disaggregation of platelet clumps formed on collagen strip superfused with blood of anaesthetized cats. This effect was completely blocked by pretreatment of cats with 50 mg/kg of acetyl salicylic acid. Disaggregatory substance formed in cat's blood disappeared when blood had been passed through silicone coil warmed to 37 degrees C for 15 min. None of the tested substances had any disaggregatory activity when applied directly on collagen strip. It is postulated that the effect of nicotinic acid derivatives is mediated by prostacyclin which they release. PMID- 6242067 TI - [Intercellular cooperation in the physiological immunologic response; clinicians on the facts and hypotheses]. PMID- 6242069 TI - [Time series analysis of tidal volume and inspiratory and expiratory duration]. PMID- 6242068 TI - Isolation of in vitro synthesized covalently closed circular double-stranded DNA by selective denaturation and filtration. AB - Based upon their resistance to irreversible denaturation, covalently closed circular (CCC) DNA (non-nicked, double-stranded circular molecules) can be purified by alkaline denaturation, neutralization, and filtration through a nitrocellulose membrane. This procedure offers a simple means of isolating in vitro synthesized CCC DNA molecules. The preparations of molecules obtained by this method consisted of 91-97% CCC DNA and contained no detectable inhibitors of biological activity or enzymatic digestion. PMID- 6242070 TI - [Absenteeism due to backache in a shipyard]. PMID- 6242071 TI - [Handicapped patients in a provincial dental clinic]. PMID- 6242072 TI - [Inguinal hernia in women: a complication of pregnancy or labor. Apropos of 160 cases of surgically treated hernias]. AB - The authors undertook a computerised retrospective study of 10 years of hernia surgery. Analysis of the specific characteristics of hernias in women provided numerical data concerning a number of classical data and in particular revealed the role of multiple gestation (more than 3 pregnancies) in the aetiology of inguinal hernias. Results of different surgical techniques are reported: herniorrhaphy procedures (e.g. the MacVay operation which should perhaps be abandoned to give way to the Shouldice procedure) retain a wide role in women. The Dacron mesh prosthesis, with an additional risk of infection of 0.5 to 3.7% offers long term reliability (98.5% cure rate) which cannot be hoped for with any herniorrhaphy procedure when repairing the most difficult hernias. The authors suggest that gynaecologists and obstetricians should continue the study or physiopathological mechanisms causing hernias since they alone would be capable of undertaking such a prospective study. PMID- 6242073 TI - Topical clindamycin versus oral tetracycline and placebo in acne vulgaris. AB - Eighty-seven patients with moderate to severe acne were included in an 8-week randomized double-blind study to compare the efficacies of topically applied clindamycin phosphate 1% b.i.d., oral tetracyclines 500 mg b.i.d. and placebo. Patients were examined every 2 weeks and inflammatory lesions, i.e. papules and pustules were counted in the same area at each examination. Clindamycin phosphate demonstrated a highly significant 72% decrease of inflammatory lesions, as did tetracyclines with a 57% decrease, but not placebo (12%). Clindamycin phosphate was superior to tetracycline. No significant side effects were seen, in particular, no skin side effects. PMID- 6242075 TI - Causes, prediction and prevention of back pain at work. AB - Pain in the back and lower limbs due to lumbar disorders has a multifactorial etiology, and there is no clear relationship between the morbid pathological change observed and the symptoms experienced. Of the precipitating factors, unaccustomed heavy work, postural fatigue, and injury are common. "Back injury," however, embodies a variety of phenomena, few of which can readily be distinguished either in national statistical data or in previous epidemiologic studies. Thus the causal relationship between back pain and work is far from clear, a difficulty compounded by the prevalence of back symptoms in all groups of the population. There are few epidemiologically established methods for identifying people who are susceptible to a first attack of back pain, though, once back pain has been reported, recurrence may be predicted. Selection of the preventive approach depends on reliable information about the prevalence of back pain/discomfort, the back injury rate, sickness absence, etc; about accidents, work stoppages, job turnover, or any other pointers to the design of the workplace or work practices; and about the resulting losses of productivity and the costs of the remedy. Though the decisions are up to management, the quality of the information required is mainly an occupational health responsibility. PMID- 6242074 TI - Impact of topical clindamycin and systemic tetracycline on the skin and colon microflora in patients with acne vulgaris. AB - In a double-blind study on 20 patients with acne vulgaris, 10 patients were treated with topical clindamycin and 10 patients with oral tetracycline for eight weeks. The skin and colon microflora were determined before, during and up to eight weeks after treatment. All patients improved markedly to the same extent. Topical clindamycin caused no changes in the colon flora, whereas oral tetracycline significantly suppressed the numbers of colon bacteria and four patients were colonized by new tetracycline resistant bacteria. In patients receiving tetracycline, 40% of the skin bacteria became resistant during therapy, while the corresponding figure for clindamycin was 60%. The skin flora was normalized in most patients after the treatment had stopped. PMID- 6242076 TI - Cardiac pathology in 47 patients with beta thalassaemia/haemoglobin E. AB - Autopsy protocols and heart slides of 47 patients with beta thalassaemia/haemoglobin E disease were reviewed. All but 1 patient had cardiac hypertrophy, accompanied by dilatation in 17; 5 of 9 patients (56%) with right ventricular and 11 of 22 patients (50%) with biventricular hypertrophy had chronic pulmonary thromboembolism. Cardiac iron deposition while present in 15 patients (32%) was very slight, in contrast to the amount of iron in their liver and pancreas. Four patients had fibrinous pericarditis, 2 with rheumatic heart disease. Twelve patients had chronic pericardial changes, 7 with adhesive pericarditis. The effects of cardiac pathology on the morbidity and mortality of patients with beta thalassaemia/haemoglobin E disease were discussed. PMID- 6242077 TI - [Uroflowmetry in the diagnosis of urination pathology in women. Preliminary report]. PMID- 6242078 TI - New organization of curative assistance for patients suffering from septicaemia. PMID- 6242079 TI - [Pelvic instability. Changed treatment of pelvic instability in the last year]. PMID- 6242080 TI - [Pelvic instability. Prejudice will disappear in time with added knowledge]. PMID- 6242081 TI - [Pelvic instability. We have written from our own experience]. PMID- 6242082 TI - Prognostic factors in adult patients with acute leukemia. AB - An analysis of prognostic factors was performed on a series of 50 adult patients with acute leukemia, treated in our department in the Tokai university Hospital between July, 1975 and June, 1980. The diagnosis was made in all cases on the basis of May-Grunwald-Giemsa-stained smears of peripheral blood and bone marrow. The patients were treated with two successive protocols. One course of induction chemotherapy consisted of 40 units/kg/day of neocarzinostatin, 1.2-1.6 mg/kg/day of cytosine arabinoside, 0.6-0.8 mg/kg/day of daunorubicin and 0.8-1.6 mg/kg/day of prednisolone on days 1-4 for acute nonlymphocytic leukemia, and the other consisted of 0.04 mg/kg/day of vincristine on day 1, 0.6-0.8 mg/kg/day of daunorubicin on days 1-4, 0.8-1.6 mg/kg/day of prednisolone on days 1-4 for acute lymphocytic leukemia. Consolidation and intensification therapies were given every 1-2 months after complete remission, and the protocols were basically the same as those of the induction therapy. Maintenance therapy consisted of 1.2-1.6 mg/kg/day of cytosine arabinoside, twice a week or 2 mg/kg/day of 6 MP orally. Risk factor leading to poor prognosis of acute leukemia were considered to be (1) advanced age (older than 50 years, P less than 0.05), (2) M5 (monocytic leukemia), (3) thrombocytopenia (less than 50,000 cmm-1), and (4) chromosome abnormalities of blast cells. PMID- 6242084 TI - A potential second messenger role for arachidonic acid: activation of Ca2+ dependent protein kinase. AB - A widely distributed Ca2+- and phospholipid-dependent protein kinase, protein kinase C, may play a major role in cellular regulation. We now report that arachidonate can directly activate protein kinase C from human neutrophils. Activation was Ca2+-dependent and was enhanced by diolein, but did not require phosphatidylserine. Arachidonate enhanced the apparent affinity of the kinase for Ca2+ in the presence of phosphatidylserine. Other unsaturated, but not saturated, fatty acids also activated protein kinase C. These results suggest a novel means of leukocyte activation and cellular regulation: arachidonate, which is released by ligand-receptor interactions in neutrophils and many other cell types, could function as a second messenger via activation and modulation of protein kinase C. PMID- 6242083 TI - Norfloxacin and silver norfloxacin in the treatment of Pseudomonas corneal ulcer in the rabbit. AB - Norfloxacin is a new synthetic antibiotic with a broad spectrum of activity against gram-positive and gram-negative bacteria, and is more effective than the aminoglycosides against P aeruginosa. In this study norfloxacin was particularly effective in treatment of P aeruginosa infection of the rabbit cornea, and caused no toxicity in normal rabbit eyes after prolonged administration. The addition of silver to norfloxacin enhances its antipseudomonal activity, and broadens its spectrum to include antifungal activity. In this study, silver norfloxacin appears to be the most effective antibiotic against P aeruginosa corneal ulcer in the rabbit. Because of its broad antibacterial spectrum, silver norfloxacin may be useful in the initial treatment of bacterial corneal ulcer before the identity of the bacteria is known. Because of its low toxicity in topical administration, and its antifungal and antibacterial activity, silver norfloxacin may be helpful in prophylaxis against infection in chronic corneal ulcers. PMID- 6242085 TI - CR1 deficiency in patients with Hansen's disease. PMID- 6242086 TI - Ligand effects on actin activated ATPase of cardiac and skeletal muscle myosin: the functional role of the light chain isozymes of subfragment-1. PMID- 6242087 TI - [Hodgkin's disease and the liver. Study of 50 biopsies]. AB - A study of 50 liver biopsies (LB) is presented from a series of 45 patients with Hodgkin's disease as diagnosed by node biopsy in 40, by laparoscopic liver biopsy (LLB) or surgery in 5, with a simultaneous positive bone marrow study in one case. A total of 34 LLB and 16 blind liver biopsies were carried out For diagnosis of the disease the LB was positive in 2/7 or 28.5%. In order to establish the clinical status as a pre-treatment staging procedure in 30 cases, the biopsy was useful in 10% of the cases; whereas during the evolution of the disease in order to establish restaging in 13 patients, positivity was observed in 1 case (7.6%). In 7/34 with laparoscopic changes of the hepatic surface, invasion was later determined by LLB, surgery or autopsy in 71%, whereas with a normal surface infiltration was only established in 18.5% In 12 patients with liver invasion as demonstrated by LLB, laparotomy or autopsy, alkaline phosphatase was increased in 91.6%. We consider that the elevated number of false negatives (58.3%) is due fundamentally to the single biopsy technique performed some years ago with the Vim-Silverman needle instead of the procedure in use at present o repeated biopsies in both lobes when possible. Our experience of 50 LB in these 45 patients has been most useful in arriving at a diagnosis in 2, determining a change in stage on 3 occasions, demonstrating peritoneal and spleen involvement in 2 cases in addition to revealing other hepatic alterations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 6242088 TI - Functional differentiation of rabbit peritoneum. Investigations in vitro. PMID- 6242089 TI - [Huntington chorea: psychological and informative aspects (study of a family over 7 generations)]. PMID- 6242090 TI - [Address delivered by the Rector of the Pomeranian Medical Academy at the inauguration of the academic year 1983-84]. PMID- 6242092 TI - [Usefulness of thin-needle aspiration biopsy in stomatological surgery]. PMID- 6242091 TI - [Evaluation of renal maturity in full-term and premature neonates]. PMID- 6242093 TI - [Effect of ultraviolet rays on levels, biosynthesis and inactivation of histamine in rabbits]. PMID- 6242094 TI - [Effect of ultraviolet irradiation on adrenaline and noradrenaline levels in the plasma, adrenal glands, brain stem and myocardium of rabbits]. PMID- 6242095 TI - [A clasp fixed in incisions on the buccal side of deciduous teeth]. PMID- 6242096 TI - [Possibilities of preventing fissure caries of first molars in children 6 to 7 years of age]. PMID- 6242097 TI - [Effect of the topical use of acidulated fluoride solutions on selected parameters of the masticatory system of school children from areas with optimal and trace concentrations of fluorides tap water]. PMID- 6242098 TI - [Experimental studies on the regeneration of autotransplants in dogs with splenic injuries]. PMID- 6242099 TI - [Results of treatment of chronic exudative inflammation of the knee joint by isotope synoviorthesis using P-32 in the light of our studies]. PMID- 6242100 TI - [Effect of piracetam (Nootropil) on the bioelectric function of the brain in cases of low-voltage EEG and in patients with epilepsy]. PMID- 6242101 TI - [Use of homologous vaccine in Pseudomonas aeruginosa infection of the urinary tract in rats]. PMID- 6242103 TI - Sibs of children with chronic conditions: counseling considerations. PMID- 6242102 TI - Cerebrospinal fluid and peripheral blood lymphocyte subpopulations in multiple sclerosis. Evaluation by means of monoclonal antibodies (a preliminary note). AB - We are investigating peripheral blood and cerebrospinal fluid lymphocyte subpopulations in multiple sclerosis patients by monoclonal antibodies directed at T-helper, T-suppressor and total mature T-cell subsets. Patients affected by other neurological diseases are also being studied as a control population. Antibodies' selectivity together with careful cell handling, allowed us a detailed study even of small lymphocyte numbers usually recovered from multiple sclerosis cerebrospinal fluid. First results point to a marked increase in T helper population, with a helper/suppressor imbalance in MS patients' cerebrospinal fluid, but not in peripheral blood. No difference could be detected between cerebrospinal fluid and peripheral blood lymphocyte subpopulations in control patients. Further work is now needed to achieve more complete and significative results. PMID- 6242104 TI - [Pharmacognosy study of the Chinese herb drugs bai-jie-teng and hin-bu-huan]. PMID- 6242106 TI - [Application of paper chromatography and thin layer chromatography to the preparation of Chinese medicines in hospitals]. PMID- 6242105 TI - [Comparative experiment on the quality of realgar]. PMID- 6242107 TI - [Sapogenins from rootlets of Panax notoginseng]. PMID- 6242108 TI - [Analysis of bile acids]. PMID- 6242109 TI - [Constituents of Sichuan astragalus]. PMID- 6242110 TI - [Active constituents of Leontopodium leontopodioides]. PMID- 6242111 TI - [Effect of xao-ke-zheng fang on blood sugar levels of alloxan diabetic rabbits]. PMID- 6242112 TI - [Preliminary observations on the blocking effect of herba asari decoction on nerve conduction]. PMID- 6242113 TI - [Cultivation technics for Codonopsis pilosula]. PMID- 6242114 TI - [Evaluation of the postgraduate education program organized by the Division of Pediatric Dentistry of Polish Dental Association in Warsaw]. PMID- 6242115 TI - [The clinical pattern of Down's syndrome]. PMID- 6242116 TI - [2-year clinical follow-up after application of Concise Enamel Bond System for sealing defects in the occluding surfaces of teeth]. PMID- 6242117 TI - Laboratory decontamination and destruction of carcinogens in laboratory wastes: some haloethers. PMID- 6242118 TI - Immune complexes and lymphocyte subset in secondary stage pityriasis rosea. PMID- 6242119 TI - Development of rapid ELISA for early serodiagnosis of dracunculiasis. PMID- 6242120 TI - Distribution of "intrastrand annealing" sequences in lambda bacteriophage genome. AB - Our computer programme which is originally developed for calculating distribution of folding structures in single stranded nucleic acids was applied for analysis of lambda phage DNA. We found that we have to choose an optimum condition of calculation depending upon what kind of structures we are looking for, for example secondary structure of transcripts or clover-leaf structures in the double stranded DNA molecules. In one calculation condition, the lambda genome was divided into two distinct regions, i.e., capsid genes with high folding probabilities. In this condition, the clover-leaf structure previously indicated in the replication origin was not detected. Calculation in the condition which included annealings with higher free energies (lower stabilities) revealed the presence of the clover-leaf structure in the DNA replication origin in the middle of the gene O. PMID- 6242121 TI - [Evaluation of the pelvioureteral function through an impedance urine bolus metry]. AB - New equipment based on field gradient principle for measurement of cross sectional area of ureteral urine bolus has been developed. Inside the probe consisted of a Fr.4 ureteral catheter, there are 4 ring impedance electrodes and a bipolar ring ureteromyographic electrode. Ex vivo experiments has proved high values in reliability and reproducibility of obtained cross sectional area of urine bolus through an impedance method. Following results have been obtained through animal and clinical experiments. As urine bolus passed through the impedance electrodes, impedance represented the cross sectional area of urine bolus. The ureteral activity corresponded to the increase of urine flow changed as follows, ureteral peristaltic frequency increased, cross sectional area of urine bolus increased, length of urine bolus increased, during maximum diuresis, peristaltic activity diminished and continuous flow presented through ureteral column. It will be useful method for experimental or clinical evaluation of ureteral function. PMID- 6242122 TI - [Actinomycosis of the abdominal wall--report of a case]. PMID- 6242123 TI - Ciprofloxacin (BAY O 9867). Comparative in vitro activity study. PMID- 6242124 TI - [Ritter's disease--staphylococcal toxic-necrotic epidermatitis]. PMID- 6242125 TI - [Morphological characteristics of virions as basic criteria of bacteriophage classification]. PMID- 6242126 TI - [Siderophores--the carriers of the iron ion]. PMID- 6242127 TI - [Drugs most frequently causing shock and skin diseases in Poland]. PMID- 6242128 TI - [Morphologic and scintigraphic correlations in the cranial localization of neuroblastoma. Study of 29 cases]. PMID- 6242129 TI - [Study on posture. Various suggestions. VI]. PMID- 6242130 TI - [Simple exploratory flowmeters in the preoperative evaluation of pulmonary function]. PMID- 6242131 TI - [Prevention of subacute bacterial endocarditis in dental practice]. PMID- 6242132 TI - [Prevention of viral hepatitis in the field of dentistry]. PMID- 6242133 TI - Serum thymic factor in active dermatomyositis. PMID- 6242135 TI - PGM1 subtypes in the Polish population. AB - Frequency of PGM1 subtypes in the sample of the Polish population numbering 197 subjects was determined by the method of isoelectric focusing. Ten subtypes were encountered. Frequencies of genes were calculated from the subtype distribution with the following results: for PGM1+1 0.698, for PGM1-1 0.058, for PGM2+1 0.180 and for PGM2-1 0.064. PMID- 6242134 TI - [Comparative evaluation of the bronchospasmolytic action of fenoterol and iprafen]. PMID- 6242136 TI - [Evaluation of T suppressor activity in systemic lupus erythematosus]. AB - Con A induced suppressor cell activity was evaluated in 10 patients with Systemic Lupus Erythematosus and in 20 normal subjects. The suppressor activity, calculated according to Shou et al. (1976), was markedly reduced in SLE patients (mean value 45.2% vs 72.9% P less than 0,01). No statistical difference was evidentiated between the patients with mild and those with severe disease, though the last ones showed the lowest values. Low degree of suppression was found related to low hemolytic complement activity (P less than 0.02) but not to anti DNA antibody titre or immune complex presence. PMID- 6242137 TI - [Follicular dendritic cells]. PMID- 6242138 TI - Treatment needs for medically handicapped children in the north district of Manchester. PMID- 6242139 TI - [Cardiac performance in dialysis patients]. PMID- 6242140 TI - [Reduction of left ventricular hypertrophy by beta-blocker treatment in essential hypertension]. PMID- 6242141 TI - The fluid silicone prosthesis. AB - Injected fluid silicone serves as a soft prosthetic device and is an effective alternative to surgery in the management of corns and calluses. The material can relieve pain in weightbearing scars, reduce the incidence of recurring neuropathic ulcers, and protect skin at points of bony pressure. Augmenting subcutaneous tissue reduces both the vertical forces that cause direct pressure and the shear stresses imposed on plantar skin during horizontal acceleration or deceleration. The only significant side effect has been fluid migration, which is asymptomatic upon weightbearing and is seen only rarely when small amounts are implanted. Histologic examination of long-term biopsy and necropsy specimens has revealed no adverse tissue response. The safety and efficacy of injectable silicone as a soft-tissue implant in the foot have not been confirmed by the Food and Drug Administration, and pending completion of authorized investigation, the material is not available. Successfully completed studies, federal approval, and proper use could provide relief for millions of people who suffer from these common foot disorders. PMID- 6242142 TI - The handicapped child. AB - In the cases presented in this article only the broad aspects were considered. Special references were made to those signs and symptoms which are usually apparent on physical examination. The purpose of these discussions is to alert the podiatric clinician to the possibility of underlying associated systemic disease for further follow-up. The major diagnostic considerations concern involvement of the lower extremities and possible treatment of these disorders. PMID- 6242143 TI - Pain-related correlates of MMPI profile subgroups among back pain patients. AB - The MMPI profiles of 96 male and 218 female patients attending a back pain clinic in a private university-affiliated, orthopedic hospital were analyzed by a hierarchical clustering procedure. The clustering procedure produced four male and four female profile subgroups. The subgroups were compared with one another on the basis of patients' responses to the Cornell Medical Index and revised McGill Pain Assessment Questionnaire. Within the male and female patient cohorts it was found that profile subgroups featuring elevated clinical scales showed greater disruptions of daily activities than did subgroups with relatively unelevated profiles. However, profile subgroups with elevations primarily on the neurotic triad scales reported greater affective disturbance and disruption of daily activities than did subgroups with elevations on both the neurotic triad and relatively psychotic scales. In addition, profile subgroups with subclinical elevations on the neurotic triad scales appeared to have adjusted to their pain experience more poorly than did subgroups that featured scores on nearly all clinical scales that were within one standard deviation of the mean. Suggestions are provided for the use of the MMPI in assessing chronic pain patients and future research regarding cluster analyses of patients' MMPI profiles. PMID- 6242144 TI - Comparison of two analogue measures for assessing and teaching assertiveness to physically disabled elderly: an exploratory study. PMID- 6242145 TI - [Biochemical structure of myelin in the central nervous system]. PMID- 6242147 TI - Hepatitis B vaccine: clinical experience. AB - Hepatitis B virus (HBV) infections occur world-wide and more than 200 million people have been estimated to be chronic carriers of HB surface antigen (HBsAg). Long-term chronic carriage of HBsAg has been associated with an increased risk of chronic active hepatitis (CAH), cirrhosis and hepatocellular carcinoma (HCC). In Western countries, the prevalence of HBV infection is low in the general population. Only particular subgroups, for the most part adults, are at risk of such infections: health care workers, haemodialysis patients, transfusion patients, drug abusers and homosexuals. In Asia and tropical Africa, however, the prevalence of HBV infection is relatively high. Transmission occurs mainly during the perinatal period and infancy. Infection at a young age often results in the chronic carrier state. A hepatitis B vaccine has been developed in France and has been demonstrated to be safe, immunogenic, and effective in preventing HBV infection. Extensive experience from clinical trials now makes it possible to recommend vaccination strategies in terms of target populations and of optimal schedules. This paper reports the results of hepatitis B vaccination and, in particular, presents an overview of the vaccination experience in newborns and children. PMID- 6242146 TI - Analysis of membrane and cytosolic phorbol ester receptors. AB - Specific phorbol ester receptors are found in the particulate fraction of cells. In addition, cytosol contains a phorbol ester apo-receptor, which requires phospholipids for reconstitution. The apo-receptor corresponds to protein kinase C, and the quantitatively major membrane receptor appears to be a protein kinase C-phospholipid complex. The ability to reconstitute the phorbol ester apo receptor into different lipid domains now makes it possible to begin elucidation of the role of the lipid domain in phorbol ester action. Studies reviewed here indicate that diglycerides competitively inhibit phorbol ester binding, consistent with their being the postulated endogenous phorbol ester analogues. Highly lipophilic phorbol esters inhibit effectively only if they are incorporated into the lipid phase, indicating that it is the membrane-dissolved form of the ligand which is recognized. The binding affinity of 3H-phorbol 12,13 dibutyrate for holo-receptor depends markedly (greater than 20-fold range) on the phospholipid environment, and heterogeneous phorbol ester binding (i.e., curved Scatchard plots) can be generated by use of heterogeneous lipid environments in the reconstitution. The possible existence of other phorbol ester receptors in addition to protein kinase C-phospholipid complexes remains to be resolved. PMID- 6242148 TI - Hepatitis B vaccine in developing countries: problems and prospects. AB - Hepatitis B vaccines are highly immunogenic. To determine the efficacy of low doses and of the intradermal route of vaccination, 197 Nigerian children were given 3 monthly doses of Hevac B. Of these, 96 had 2 micrograms subcutaneously and 101 had 2 micrograms intradermally. One month after completing the schedule, 82.3% and 74.3% of the respective groups had become anti-HBs positive without adverse side-effects. In the second part of the study, 50 chronic HBsAg carriers were vaccinated. Compared to placebo-treated carriers, no effect was demonstrated with regard to HBsAg clearance or anti-HBs production. Immune complexes were not attributable to Hevac B. No untoward effects were noted. Booster vaccination of 50 initial non-responders resulted in the development of significant levels of anti-HBs in 20 (40%) of the recipients. None of the 'non-responders' developed clinical or virological evidence of HBV infection. It is concluded that low-dose vaccination is effective and that the intradermal route may be useful in developing countries. PMID- 6242149 TI - [Vaccination of the newborn against hepatitis B in Burundi]. AB - Vaccination against hepatitis B is carried out at birth in the Bujumbura Hospital in Burundi. The vaccination protocol comprises only two injections, the first being given during the first 48 hours after birth and the second two months later. A booster is given at the age of one year. The results of this vaccination programme are compared with those obtained in a control population. At the time of the booster, 82% of vaccinated subjects had anti-HBs antibodies, compared with 3% of control subjects. Six months after the second injection, all vaccinated subjects had anti-HBs antibodies. PMID- 6242150 TI - Immune response to hepatitis B vaccine in infants and newborns: control trial in an endemic area (Senegal). AB - In 1978 it was suggested that hepatitis B (HB) vaccine should be used to prevent the early hepatitis B surface antigen (HBsAg) carrier state in children. Immunization was effected by 3 injections of HB vaccine at one-month intervals followed by a booster injection after one year. Children in a control group were immunized with DT-polio vaccine according to the same schedule. The anti-HBs response of the children to HB vaccination was studied in relation to their hepatitis B virus (HBV) serum markers prior to immunization. Of the seronegative children, 70.5% responded to immunization after 2 injections of 5- g doses of HB vaccine and 94% after the third injection. The efficacy of the vaccine was demonstrated by comparison of HB events after one year in 309 seronegative children immunized with HB vaccine and 252 seronegative children immunized with DT-polio vaccine, and after two years in 101 and 119 children, respectively. The incidence of the HBsAg carrier state was reduced by 80% in susceptible children. In order to eliminate the perinatal transmission occurring in newborns with HBsAg positive mothers, a study of immunization at birth has been instituted. A total of 86 newborns responded to the vaccination as well as older children, irrespective of the HBV status of their mothers. After one year, the incidence of the HBsAg carrier state was reduced by 80%. In Africa, immunization teams have a limited amount of time to devote to each rural community. The immunogenic effect of 2 doses of HB vaccine given at an interval of 2 or 6 months has therefore been investigated. All were given a booster dose one year after the first injection of vaccine. No difference was observed in the seroconversion rate or in the anti-HBs titres as between the two protocols. These results demonstrate that 2 doses of 5 micrograms of HB vaccine are sufficient to obtain a high immunogenic effect in infants. In addition, an investigation was carried out on the immune response to HBsAg and tetanus toxoid antigen when administered simultaneously to children as HB vaccine and DT-polio vaccine. The immune response was at least equal to that observed after administration of these vaccines separately. PMID- 6242151 TI - Use of hepatitis B virus vaccine in Africa: rationale and practical approaches for effective utilization. AB - This report considers the following questions: (1) Should hepatitis B virus (HBV) vaccine be used in Africa, if and when adequate supplies become available at an affordable cost? (2) Who should receive the vaccine and when? (3) What type of HBV vaccine should be used? Answers to these questions are suggested based on a review of available knowledge of the epidemiology of HBV infections in Africa, the role of HBV in the etiology of hepatocellular carcinoma and cirrhosis, and the utilization of various currently available and experimental HBV vaccines. PMID- 6242152 TI - The influence of self-ascribed handicapped status on the positive and negative affect of the elderly. AB - Recently, Stock and Okun found that self-ascribed handicapped elders, relative to self-ascribed nonhandicapped elders, had significantly lower mean scores on six measures of subjective well-being. Using the same data base, in the present study, we examined whether self-ascribed handicapped status accounted for variance in positive and negative affect, net of intra- and interpersonal resources, and social status. On the bivariate level, self-ascribed handicapped status was related significantly to positive and negative affect. However, it did not account for more than 2 percent of the variance in either. As anticipated, self-ascribed handicapped status was not a significant predictor of positive and negative affect when social status and intra- and interpersonal resources were statistically controlled. Contrary to expectations, social status was a unique predictor of positive and negative affect. PMID- 6242153 TI - A link between transport and plasma membrane redox system(s) in carrot cells. AB - Carrot (Daucus carota L.) cells grown in suspension culture oxidized exogeneous NADH. The NADH oxidation was able to stimulate K+ (86Rb+) transport into cells, but it did not affect sucrose transport. N,N'-Dicyclohexyl-carbodiimide, diethylstilbestrol, and oligomycin, which only partially inhibited NADH oxidation, almost completely collapsed the K+ (86Rb+) transport. Vanadate, which is less effective as an ion transport inhibitor, was less effective in inhibiting the NADH-driven transport of K+ (86Rb+). p-Fluormethoxycarbonylcyanide phenylhydrazone inhibits the K+ transport over 90% including that induced by NADH. The results are interpreted as evidence that a plasma membrane redox system in root cells is closely associated with the ATPase which can drive K+ transport. Because of the inhibitor effects, it appears that membrane components common to the redox system and ATPase function in the transport of K+. PMID- 6242155 TI - [Pre-ejection flow in the left ventricular outflow tract elucidated by pulsed Doppler technique]. AB - Pulsed Doppler technique has elucidated the blood flow towards the cardiac base in the left ventricular (LV) outflow tract prior to onset of ejection flow. This pre-ejection flow (PE flow) is observed immediately after the beginning of atrial contraction and it lasts until immediately after completion of mitral closure. This study was designed to clarify the mechanism and physiological significance of PE flow by investigating the temporal relationship between PE flow and cardiac dynamics and by examining its velocity distribution in the LV outflow tract. Observations were made for 21 healthy subjects (H), 12 patients with atrial fibrillation (Af), three with first degree AV block and two with second degree AV block of the Wenckebach type. A Doppler-Echocardiograph (Hitachi Medico EUB-10B) was used, and PE flow was detected in all subjects. The Doppler frequency, which corresponded to blood flow velocity, increased when the sampling site was near the tip of the anterior mitral valve leaflet as opposed to the upper portion of the LV outflow tract. Results of the temporal analysis of PE flow were as follows: The PE flow pattern was monophasic both in H and patients with Af. Its peak appeared 0.18 +/- 0.05 (mean +/- SD) sec after the beginning of the P wave and 0.02 +/- 0.02 sec after the Q wave in H, but 0.06 +/- 0.01 sec after the Q wave in Af. In first degree AV block, the PE flow consisted of two peaks. The interval between the first PE flow peak and the beginning of the P wave was constant and nearly 0.2 sec apart. It was nearly the same as in H. The second peak occurred 0.05 sec after the Q wave as in Af. In second degree AV block of the Wenckebach type, the first peak occurred at constant interval following the P wave, while the second peak related to left ventricular contraction and disappeared when an atrial contraction failed to initiate a ventricular response. These findings indicate that PE flow consists of two components with different mechanisms. 1) The first component is caused by the atrial blood inflow turning up from the apex towards the cardiac base. This flow component may participate in closure of the anterior mitral leaflet. 2) The second component consists of a rise in LV pressure due to LV contraction, and achieves complete closure of the mitral leaflets. We conclude that PE flow with its atrial and ventricular components contributes to closure of the mitral leaflets. PMID- 6242154 TI - [The heart in acromegaly: an echocardiographic study]. AB - Clinical examinations including echocardiography were performed for 14 acromegalic patients (five men and nine women, whose mean age was 48.6 years). Three of these had hypertension (HT) above 160/95 mmHg, three had diabetes mellitus (DM). Their cardiac sizes and functions were correlated with the durations of disease and plasma growth hormone (GH) levels. The incidences of HT and DM were also evaluated. Three of 14 patients (22%) had increased cardiothoracic ratios (greater than 55%). Electrocardiographic abnormalities were noted in three patients including two with left ventricular hypertrophy (LVH) and one with interventricular conduction defects with abnormal Q waves. By echocardiography (Table 2), nine patients (64%) were judged to be normal. The remaining five patients (36%) had abnormal echocardiograms. These included LVH (sums of the interventricular and posterior wall thicknesses greater than or equal to 25 mm) in two (25 mm in Case 10, 30 mm in Case 11), increased left ventricular end-diastolic dimension (EDD greater than or equal to 55 mm) in one (72 mm in Case 14) and both abnormalities in two patients (Cases 12 and 13). Two patients (Case 13 and 14), whose %FS were 17% and 22%, respectively, had definite evidence of congestive heart failure. Two patients (Case 11 and 13) met the diagnostic criteria for asymmetric septal hypertrophy. One patient with echocardiographic LVH and another who had increased EDD with LVH had histories of HT (Case 11 and 12). Plasma GH levels in patients with LVH were greater than 100 ng/ml (Cases 10 and 11). The left ventricular hypertrophy and/or increased EDD observed in these patients seemed related to the duration of acromegaly but not to the presence of DM. Myocardial biopsy of the right ventricle in two patients with congestive heart failure disclosed myocardial hypertrophy, myocardial fiber disarray, interstitial fibrosis and large nuclei. PMID- 6242156 TI - [Magnetocardiography: a comparison with electrocardiography]. AB - Magnetocardiogram (MCG) was recorded for normal subjects and patients with right or left ventricular hypertrophy using a second derivative superconducting interference device (SQUID) gradiometer and the results were compared with those of electrocardiogram (ECG). MCG with a second derivative gradiometer localized current sources more easily than did ECG. Therefore, the waveforms of the MCG varied more than ECG dependent on recording sites. The current source near the anterior chest wall was detected readily, as this gradiometer measures the spatial differentiation of the magnetic field. In normal subjects, dipoles located on the right and directed to the right and superiorly, apparently of right ventricular origin, appeared earlier and were more clear than with the ECG. In addition, in patients with right ventricular overloading, MCG reflected an increased force to the right more clearly. In patients with left ventricular hypertrophy, MCG showed the T wave inversion more frequently than did ECG. The electromotive forces deduced from isomagnetic and vector arrow maps were in good agreement with the excitation sequences of previous reports. MCG could detect multiple dipoles by these maps, especially opposing dipoles which were difficult to detect by ECG or isopotential maps. These results suggested that MCG provides information different from ECG. Thus, the use of MCG in addition to ECG might be helpful in determining the current sources more accurately. PMID- 6242157 TI - [Percutaneous transluminal coronary angioplasty and intra-operative angioplasty]. AB - Percutaneous transluminal coronary angioplasty (PTCA) was reviewed with respect to its history, principles, indications and complications. We also reported our experiences with this technique. PTCA was useful in selected cases, but we encountered eight complications among 90 procedures; namely, coronary spasm, coronary dissection and recurrent stenosis. Since 1980 we have used this transluminal angioplasty for 16 patients during aorto-coronary bypass grafting surgery. We also discussed preliminary results in the use of this newly developed technique. PMID- 6242158 TI - Human in vitro fertilization and embryo transfer at the University of Texas, Houston. AB - The current clinical and laboratory protocols of the in vitro fertilization program at the University of Texas at Houston are described and detailed. Most patients treated have tubal disease, with a limited number of couples having male factors. Clomiphene citrate (50 mg/day, cycle days 5-9) with or without added menopausal gonadotropins is the principle agent for enhanced follicular recruitment. Follicular development is monitored primarily with daily ultrasonography, and human chorionic gonadotropin (hCG) is given when the largest follicle reaches or exceeds 20-mm mean diameter. The culture media used are modifications of Ham's F-10. Mature oocytes are preincubated for 5 hr before insemination with 50,000 motile sperm per oocyte. Using these protocols, the clinical pregnancy rate is 11.6% per laparoscopy (11/95) and 16.2% per embryo transfer (11/68). PMID- 6242160 TI - Organization and computerized analysis of in vitro fertilization and embryo transfer programs. AB - The in vitro fertilization experience of one of the earliest successful programs is presented based on three different center types: (I) large hospital university, (II) private gynecological office, and (III) egg-embryo transfer from and to centralized laboratory. A computerized analysis of systems I and II for 1982 is presented. No statistically different results were found between system I and system II. System III was abandoned because of unsatisfactory results. PMID- 6242159 TI - Factors influencing the success of in vitro fertilization for alleviating human infertility. AB - The program for in vitro fertilization at Bourn Hall began in October 1980. Various types of infertility have been treated during this time using the natural menstrual cycle or stimulation of follicular growth with antiestrogens and gonadotrophins. Follicular growth and maturation are assayed by urinary estrogens and LH, monitored regularly during the later follicular stage. Many patients had an endogenous LH surge; others needed an injection of HCG to induce ovulation. All oocytes were recovered by laparoscopy. Wide variations occurred in the time interval between the start of the LH surge and oocyte recovery and between oocyte recovery and insemination. Embryos taken between the one- and the eight-cell stage were replaced into their mother, no standard procedure being adopted for all patients. The results of all treatments including patient's responses during the follicular and luteal phases, oocyte recovery, fertilization, cleavage, replacement, implantation, abortion, and birth and the effect of factors such as replacing two or more embryos, maternal age, and previous obstetric history are described in detail. The incidence of implantation after embryo replacement improved from 16.5% initially to 30% currently. More than 118 babies have been born, and many pregnancies are continuing. PMID- 6242161 TI - In vitro fertilization and embryo transfer program in Clamart, France. AB - Our in vitro fertilization and embryo transfer program really began in September 1980. Yet attempts to collect oocytes had been performed since 1978, and the first in vitro fertilizations were obtained in May 1979. The first pregnancy was obtained in April 1981, but it ended on the 12th week by a spontaneous abortion of a 45,X fetus. We have distinguished two periods in our program. The initial phase was from September 1980 until November 1982: ovulation monitoring of 365 cycles, spontaneous or stimulated, 276 laparoscopies, and 121 embryos transfers were performed, and 12 early pregnancies obtained (4.3% per laparoscopy and 9.9% per embryo transfer). Seven normal healthy infants were born (five boys and two girls); four cases were limited to biochemical pregnancies and one spontaneous abortion (yet described) was observed. The second and actual phase, December 1982 June 1983, is described more precisely: ovulation monitoring of 329 cycles, after stimulation protocols with clomiphene citrate and human menopausal gonadotropin, 230 laparoscopies, and 162 embryos transfers have been performed and have led to 34 pregnancies (14.8% per laparoscopy and 20.9% per embryo transfer). Eighteen of these 34 pregnancies are actually in progress (more than 12 weeks), 9 were limited to an increase in plasma human chorionic gonadotropin, and 7 cases ended in spontaneous abortions between 6 and 12 weeks. PMID- 6242162 TI - In vitro fertilization and embryo transfer program, Department of Obstetrics and Gynecology, University of Adelaide at the Queen Elizabeth Hospital, Woodville, South Australia. AB - A review is presented summarizing the in vitro fertilization experience at the University of Adelaide, Australia. Initial attempts utilizing the normal cycle were unsuccessful in obtaining a pregnancy. Since 1982 the overall ongoing pregnancy rate has been 21% per embryo transfer, 16% per laparoscopy, and 12% per treatment cycle. A detailed description of presently utilized methodology is presented. PMID- 6242164 TI - University of Chicago in Vitro Fertilization Program at Michael Reese Hospital and Medical Center. PMID- 6242163 TI - Implementation of an in vitro fertilization program. AB - The establishment of an in vitro fertilization program is described. Organization of the physical laboratory, media formulation, and preliminary mouse embryo culture are discussed. Parameters of patient eligibility, ovarian stimulation, and laparoscopy are also defined. At the conclusion of Phase I, 17 patients were induced; 10 went to laparoscopy, and at least one four-cell embryo was returned to 7, resulting in one continuing pregnancy. PMID- 6242165 TI - Laparoscopic or ultrasonically guided follicle aspiration for in vitro fertilization? AB - Ultrasonically guided follicular aspiration is presented as an alternative method to laparoscopy for oocyte harvesting. The method is described in detail and compared to laparoscopic oocyte pickup. The success rate of this technique reached in 1984 compared to that of laparoscopic oocyte pickup was the same: the oocyte recovery rate was 93%, the fertilization rate was 58%, and the pregnancy rate was 13% (normal ongoing pregnancies per treatment cycle). Ultrasonically guided follicular aspiration is shown to be superior to laparoscopic oocyte recovery as far as ovarian accessibility and complication rate are concerned. PMID- 6242166 TI - Dental treatment of patients with myasthenia gravis. PMID- 6242167 TI - Phenotypic heterogeneity in Huntington disease. AB - Two Huntington disease (HD) pedigrees are presented which differ according to mean and distribution of the age at onset, the effect of paternal transmission on the age at onset, presence of manic-depressive symptoms, and type of presenting symptoms. Together with previous reports, the data suggest clinical heterogeneity between HD kindreds which may imply some kind of genetic heterogeneity, most likely subsequent mutation at a single HD locus. The possibility of genetic heterogeneity has important consequences, both in research, and in the counseling and care of families and patients with differing manifestations of the disease. PMID- 6242168 TI - Primeval cells: possible energy-generating and cell-division mechanisms. AB - It is proposed that the first entity capable of adaptive Darwinian evolution consisted of a liposome vesicle formed of abiotically produced phospholipidlike molecules; a very few informational macromolecules; and some abiogenic, lipid soluble, organic molecule serving as a symporter for phosphate and protons and as a means of high-energy-bond generation. The genetic material had functions that led to the production of phospholipidlike materials (leading to growth and division of the primitive cells) and of the carrier needed for energy transduction. It is suggested that the most primitive exploitable energy source was the donation of 2H+ + 2e- at the external face of the primitive cell. The electrons were transferred (by metal impurities) to internal sinks of organic material, thus creating, via a deficit, a protonmotive force that could drive both the active transport of phosphate and high-energy-bond formation. This model implies that proton translocation in a closed-membrane system preceded photochemical or electron transport mechanisms and that chemically transferable metabolic energy was needed at a much earlier stage in the development of life than has usually been assumed. It provides a plausible mechanism whereby cell division of the earliest protocells could have been a spontaneous process powered by the internal development of phospholipids. The stimulus for developing this evolutionary sequence was the realization that cellular life was essential if Darwinian "survival of the fittest" was to direct evolution toward adaptation to the external environment. PMID- 6242169 TI - [Necessity for total trichloride compound measurement in screening tests for workers exposed to trichloroethylene or 1,1,1,-trichloroethane]. AB - In 9 series of physical examinations legally required for trichloroethylene (TCE) workers, levels of urinary total trichloride compounds (TTC) were revealed to be generally high in 323 specimens, including 250 male ones, collected from a medium sized company. Sixty four specimens (19.8%), including 56 male ones (22.4%), exceeded 300 mg/l which are regarded to correspond to the threshold limit for TCE in the air of the work site. Four specimens had over 900 mg/l. In all 323 specimens, however, no abnormalities were found with respect to specific gravity of blood, hemoglobin concentration and urinary tests. TTC concentration values increased in specimens in the last 4 physical checkups, compared with the values measured in the first 5. The cause of this increase seemed to be related to increases in the number of products and the hours of overtime work. Symptoms felt by these workers gradually subsided as they were continuously exposed to TCE for more than 2 or 3 years. Some workers of long service had a tendency toward addiction to TCE. In the legally required environmental monitoring of TCE, and other harmful organic solvents, the 8 workplaces fell into either classification 1 or 2, indicating that the environmental conditions are not harmful. More importantly, the above evaluations did not take into account long hours of overtime put in by those workers. Turning to the checkups of 1,1,1 trichloroethane workers, the results of legally required physical checkups and environmental monitoring were almost the same as those for TCE.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 6242170 TI - [Bronchial asthma due to inhaled chloroplatinate]. AB - Platinum and its compounds have characteristics that make them excellent oxygen sensors, and in recent years they have come to be used in large amounts in the manufacture of internal combustion engines. Recently, there have been detected among workers engaged in making platinum oxygen sensors, dermatitis and bronchial asthma which appear to be ascribable to exposure to chloroplatinate. This is a study of their etiology from the viewpoint of industrial hygiene and clinical medicine. The results obtained are as follows: Platinum-induced allergic disorders developed in a worker who applies about 50% chloroplatinate to zirconia porcelain. Although the concentration of platinum in the air was 2 microgram/m3 or less as determined by ACGIH, the worker was directly exposed to the dried powder of ammonium chloroplatinate with relatively high concentration; while the exposure was intermittent and topical, it resulted in aspiration of the powder. Bronchial asthma observed in 2 of 16 workers (12.5%) was reactive in a skin drop test with 1% chloroplatinate, and typical bronchial asthma was induced in an environmental provocation test carried out in a room where platinum sensors are made. Parameters obtained from periphero-hematological and immuno-serological tests were within the normal range. The main symptoms revealed by physical examination of workers exposed to chloroplatinate contact dermatitis in 11 (78.6%), pharyngeal irritation in 6 (42.9%), nasal obstruction in 2 (14.3%), frequent sneezing, coughing, and sputum in one each.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 6242171 TI - An orthopedic ethnography in rural Nepal. PMID- 6242172 TI - [Periodontal conditions in patients with trisomy 21: review of the literature]. PMID- 6242173 TI - [Dento-periodontal pathology in a group of adult patients with Down's syndrome]. PMID- 6242174 TI - [Histologic evaluation of the characteristics of tissue biocompatibility of 4 materials used in endodontics]. PMID- 6242175 TI - [Orthodontic treatment in patients with hemophilia. Preliminary note]. PMID- 6242176 TI - [Minor oral surgery in heart disease patients in drug therapy or patients with previous surgical therapy]. PMID- 6242177 TI - [Focal diseases of orodental origin]. PMID- 6242178 TI - [Preincubation in trypticase soy agar for counting Staphylococcus aureus in chlorinated pool water]. PMID- 6242179 TI - Chronic pain: a chronic dilemma. PMID- 6242180 TI - Peripheral and coronary angioplasty. PMID- 6242181 TI - Renal angioplasty. PMID- 6242182 TI - [Bone scintigraphy in total isoelastic hip prosthesis. Proposal of a semiquantitative analysis]. AB - The authors present a method of semiquantitative analysis of bone scintigraphy in the study of the evolution of total hip prosthesis and analyse the course of remodelling processes in a group of patients who showed no post surgical complication after total isoelastic hip arthroplasty without cement. The authors will use data worked out as terms of comparison in the study of those patients who present, after surgery, a symptomatology difficult to be evaluated in order to discriminate the cases where the symptoms indicate the beginning of a pathologic process (loosening and/or infection). PMID- 6242183 TI - [Primary aspects of radiological examination in prosthetic therapy. I. Control of clinical preparations and adaptation of abutment crowns]. PMID- 6242184 TI - [Fluorides still in current use]. PMID- 6242186 TI - [Report of 2 cases of dentin dysplasia]. PMID- 6242185 TI - [Space maintenance appliances]. PMID- 6242188 TI - [A combined maxillary prosthetic restoration of apparent simplicity]. PMID- 6242187 TI - [The early orthodontic treatment in a group of preschool children]. PMID- 6242189 TI - [Efficiency and preventive effect of topical fluorides applied with a custom designed device]. PMID- 6242190 TI - [Restoring the functional morphology of teeth in the lateral arch with various fillings]. PMID- 6242191 TI - [The value of arsenic in the emergency treatment of dental pulp inflammation]. PMID- 6242192 TI - [The neuromuscular occlusion concept. I. Considerations on the mandibular neuromuscular position]. PMID- 6242193 TI - [Anterior guide bar and restoration of anterior edentulousness]. PMID- 6242194 TI - [Exploration of pulp pathology using radionuclides]. PMID- 6242195 TI - [The role of computers in modernizing concepts and diagnostic methodologies in acute pulp inflammation]. PMID- 6242196 TI - [Immunologic studies in chronic marginal periodontopathies]. PMID- 6242197 TI - [Values and limits of cytological examinations in the pathology of the oro maxillofacial region]. PMID- 6242198 TI - [The value of sialography in diagnostic verification and surgical management of tumors of the parotid gland]. PMID- 6242199 TI - [Echography in the diagnosis of parotid tumors]. PMID- 6242200 TI - [Use of lasers in dentistry and maxillofacial surgery]. PMID- 6242201 TI - [Kinesiographic analysis of the mandible in occlusal dysfunction]. PMID- 6242202 TI - [Final equilibration in the treatment of dento-maxillary anomalies]. PMID- 6242203 TI - [Variation in blood sugar in diabetic patients (insulin-dependent) after loco regional anesthesia with vasoconstrictors]. PMID- 6242204 TI - Laparoscopically disclosed findings of insidious portal hypertension in a hepatitis B surface antigen carrier. AB - In a 37 year-old male, a chronic asymptomatic carrier, laparoscopic examination disclosed a thickening capsule of the liver with a whitish gray hue and congestive branches of the portal vein scattered on the thickened hepatic capsule. The congestive branches of the portal vein stood out in bold relief against the whitish gray hue and they were suggestive of portal hypertension. The subserosal vein of the gallbladder was also congested and the spleen was enlarged. These findings were related to insidious portal hypertension, though no manifestations of portal hypertension could be detected clinically. Moreover, no early history of liver disease or very few abnormal laboratory findings could be found in this case. The histology of the biopsied liver showed markedly proliferated fibrous tissue, especially in the portal areas, as well as somewhat thick septal formation. To date, many laparoscopic findings of portal hypertension were given, but this is the first report of laparoscopically detected findings in which congested branches of the portal vein were scattered and stood out in bold relief against the thickened hepatic capsule. PMID- 6242205 TI - Two cases of acute poststreptococcal glomerulonephritis superimposed on rheumatoid arthritis. AB - Recently, the rheumatoid factor (RF) has been postulated to play a role in the development of acute poststreptococcal glomerulonephritis (APSGN). However, there are few reports in which APSGN is superimposed on rheumatoid arthritis (RA). Two patients are reported in this paper who showed atypical renal histopathological findings as APSGN. It was suggested that renal histopathological finding might become different from those of typical APSGN when it is superimposed on RA. PMID- 6242206 TI - Diagnosis of osteomyelitis of mandible by 99mTc-MDP and 67Ga citrate imaging. AB - Osteomyelitis of the mandible is one of the most intractable inflammations occurring in the oral cavity. However, the recent increased incidence of subacute cases of this disease resulting probably from inappropriate use of antibiotics caused difficulties in diagnosis and management of this disease. By means of diagnostic imaging using 99mTc-MDP and 67Ga citrate, we obtained useful information for evaluation of the expansion of lesional involvement and the degree of progression, and also for prediction of the prognosis in six cases of osteomyelitis which presented different patterns of morbidity. PMID- 6242207 TI - Metabolism of tritiated C19 steroids by Shionogi mouse mammary tumors. AB - In the present report, the metabolism of dehydroepiandrosterone, 5-androstene-3 beta, 17 beta-diol and androstenedione has been studied in two different Shionogi tumors, one is androgen-dependent ("androgen sensitive") and grows in intact male mice and the other is apparently androgen-independent ("androgen insensitive") since the cells continue to grow in castrated antiandrogen (Flutamide) treated male animals. Our data clearly show that both the sensitive and insensitive tumors contain 3 beta-hydroxysteroid delta 5-delta 4 isomerase which causes the transformation of C19 steroids into potent androgenic steroids. However, the androgen sensitive tumor is able to convert 5-androstene-3 beta, 17 beta-diol into 2-hydroxyestrogens while the rate of conversion is extremely low in the insensitive tumor. Most interestingly, the production of 5 alpha-reduced steroids observed in both tissues was clearly higher in insensitive tumor homogenates. PMID- 6242208 TI - [Effect of activators and inhibitors of SH groups on purified phosphofructokinase activity in hemolysates and intact erythrocytes]. PMID- 6242209 TI - [Two new formulae for evaluating the effectiveness of drug combinations and the revision of Burgi's and Jin's modified Burgi's formulae]. PMID- 6242210 TI - [Effect of l-stepholidine on rotational behavior in rats]. PMID- 6242211 TI - Modification of the effects of repetitive restraint stress on brain biogenic amines by L-tyrosine. PMID- 6242212 TI - [Effects of the injection of morphine into the head of the caudate nucleus on the activities of neurons of the nucleus raphe magnus in rats]. PMID- 6242213 TI - [Effect of puerarin and analogues of daidzein on adrenoceptors]. PMID- 6242214 TI - [Contraction of rabbit pulmonary artery by isoproterenol]. PMID- 6242215 TI - [Central and cardiac histamine receptors involvement in the anti-arrhythmic effect of cimetidine]. PMID- 6242217 TI - [Effects of oral diltiazem on left ventricular function in patients of coronary disease]. PMID- 6242218 TI - [Effects of tetrandrine on seven vascular smooth muscles]. PMID- 6242220 TI - [Effect of gossypol acetic acid on induction of sister chromatid exchange of spermatogonial cell in mice]. PMID- 6242221 TI - [Effect of potassium deficiency on the magnesium metabolism of rats]. PMID- 6242222 TI - [Metabolic changes of phospholipids in animals fed with low selenium]. PMID- 6242223 TI - Effect of aqueous extracts of Acanthopanax senticosus on parathion toxicity in mice. PMID- 6242227 TI - Resonance in frequency spectrum of brain evoked potential. PMID- 6242224 TI - [Resin hemoperfusion for acute pentobarbital intoxication in rats and rabbits]. PMID- 6242228 TI - Analysis of electroencephalographic activity new model of the method of spontaneous and evoked activity summation in EEG. PMID- 6242229 TI - [Protease inhibitors and antifibrinolytic therapy]. PMID- 6242230 TI - Demonstration of lysogeny in stable L-forms of Staphylococcus aureus. PMID- 6242231 TI - The role of anthropometric measures on the musculoskeletal system of workers performing heavy physical work. PMID- 6242232 TI - Comments on the reliability of muscle activity comparisons in EMG biofeedback research with back pain patients. AB - The underlying assumption in comparing muscle activity levels in back pain research is the reliability of the documented biological record. Surface-recorded EMG data are often used as "objective" indicators in treatment outcome studies. The present paper questions the reliability of this somatic measure. Three sources of error variance that interfere with the reliability of the recorded biological signal are discussed: movement of the body, replacement of electrodes, and electronic equipment instability. It is argued that surface-recorded EMG activities of the back are unreliable and unsuited for comparing the efficacy of a back pain treatment program. PMID- 6242235 TI - [Left ventricular hypertrophy of experimental cor pulmonale in the rabbit]. PMID- 6242234 TI - [Surgical treatment of soft tissue sarcoma of the anterior abdominal wall]. PMID- 6242233 TI - [Effects of hepatitis B vaccine in neonates: induction of an anti-HBs immune response and interruption of maternal HBsAg transmission]. PMID- 6242236 TI - [Laparotomy by the Cohen method]. PMID- 6242237 TI - [Comparison of the course of healing of abdominal wall wound after skin suturing with ordinary single sutures and continuous intradermal suture]. PMID- 6242238 TI - Psychiatric problems affecting dental care of the elderly. PMID- 6242239 TI - Down's syndrome associated with absent patellae: a case report. PMID- 6242240 TI - [Orodental complications in alcoholism]. PMID- 6242241 TI - Dysfunctional grieving related to childbearing loss: a descriptive study. PMID- 6242242 TI - Local anesthetics: a new class of partial inhibitors of mitochondrial ATPase. AB - The following characteristics are reported for mitochondrial ATPase prepared by the chloroform extraction method: (1) The pH optimum for enzyme activity is at 8.0. (2) The neutral anesthetic benzocaine inhibits the enzyme at all pH values. (3) Reciprocal plots of 1/v versus 1/[ATP] show that inhibition by lidocaine, tetracaine, dibucaine, and chlorpromazine is noncompetitive; slope and intercept replots are hyperbolic, showing that the inhibition is partial rather than complete. PMID- 6242244 TI - Relationships of inosine triphosphate and bicarbonate effects on F1 ATPase to the binding change mechanism. AB - Two interesting previously reported properties of mitochondrial F1 ATPase have been confirmed and have been examined by 18O exchange measurements to assess if they are consistent with sequential participation of catalytic sites during ATP hydrolysis. These are the ability of HCO3- to increase reaction rate with apparent loss of cooperative interaction between subunits and the ability of ITP to accelerate the hydrolysis of a low concentration of ATP. The effect of HCO3- was tested at concentrations of ATP lower than previous measurements. The activation disappeared when ATP was reduced to 0.1 microM. The HCO3- activation at higher ATP concentrations did not change the extent of reversal of the cleavage of tightly bound ATP at the catalytic site, as measured by the average number of water oxygens incorporated with each Pi formed when 5 or 10 microM ATP is hydrolyzed. The data are consistent with sequential site participation with HCO3- acceleration of ADP departure after a binding change that stops 18O exchange and loosens ADP binding. When ITP concentration was lowered during net ITP hydrolysis by F1 ATPase an increase in water oxygen incorporation into Pi formed is observed, as noted previously for ATP hydrolysis. The acceleration of the cleavage of a constant low concentration of [gamma-18O]ATP by concomitant hydrolysis of increasing concentrations of ITP was accompanied by a decrease in water oxygen incorporation with each Pi formed from the ATP. These results add to evidence for the binding change mechanism for F1 ATPase with sequential participation of catalytic sites. PMID- 6242243 TI - Temperature dependence of mitochondrial oligomycin-sensitive proton transport ATPase. AB - The temperature dependence of the oligomycin-sensitive ATPase (complex V) kinetic parameters has been investigated in enzyme preparations of different phospholipid composition. In submitochondrial particles, isolated complex V, and complex V reconstituted in dimyristoyl lecithin vesicles, the Arrhenius plots show discontinuities in the range 18-28 degrees C, while no discontinuity is detected with dioleoyl lecithin recombinant. Van't Hoff plots of Km also show breaks in the same temperature interval, with the exception of the dioleoyl-enzyme vesicles, where Km is unchanged. Thermodynamic analysis of the ATPase reaction shows that DMPC-complex V has rather larger values of activation enthalpy and activation entropy below the transition temperature (24 degrees C) than those of the other preparations, while all enzyme preparations show similar free energies of activation (14.3-18.5 kcal/mol). The results indicate that temperature and lipid composition influence to a different extent both kinetic and thermodynamic parameters of ATP hydrolysis catalyzed by the mitochondrial ATPase. PMID- 6242245 TI - Decavanadate is responsible for vanadate-induced two-dimensional crystals in sarcoplasmic reticulum. AB - Two-dimensional protein crystals of the calcium pump protein of sarcoplasmic reticulum (SR) from fast skeletal muscle were induced using Na3VO3 as first described by Dux and Martonosi. These crystals exhibit repeat rows approximately 11 nm apart which contain discrete units with approximately 7 nm repeats. Four different methods of sample preparation for electron microscopy, i.e., negative staining, freeze-drying, freeze-fracturing, and thin-sectioning electron microscopy, each give complimentary repeat units. The SR-membrane crystals exhibit surface structure by the freeze-drying technique and row-like structures on the normally smooth outer face of normal SR. The formation of the membrane crystals is dependent on the pH and concentration of the vanadate. Only conditions favoring the presence of decavanadate yield crystals. At low concentrations and neutral pH, decavanadate is unstable and with time converts to smaller oligomers and the monomer. The presence of membrane crystals was correlated with the life span of the decavanadate. Membrane crystals were obtained in the SR membrane from fast twitch muscle from light and heavy SR, referable to longitudinal and terminal cisternae as well as from reconstituted SR. Canine cardiac SR did not crystallize under these conditions. PMID- 6242246 TI - The oligomycin sensitivity conferring protein (OSCP) of beef heart mitochondria: studies of its binding to F1 and its function. AB - The binding of "oligomycin sensitivity conferring protein" (OSCP) to soluble beef heart mitochondrial ATPase (F1) has been investigated. OSCP forms a stable complex with F1, and the F1 X OSCP complex is capable of restoring oligomycin- and DCCD-sensitive ATPase activity to F1- and OSCP-depleted submitochondrial particles. The F1 X OSCP complex retains 50% of its ATPase activity upon cold exposure while free F1 is inactivated by 90% or more. Both free F1 and the F1 X OSCP complex release upon cold exposure a part--probably 1 out of 3--of their beta subunits; whether alpha subunits are also lost is uncertain. The cold treated F1 X OSCP complex is still capable of restoring oligomycin- and DCCD sensitive ATPase activity to F1- and OSCP-depleted particles. OSCP also protects F1 against modification of its alpha subunit by mild trypsin treatment. This finding together with the earlier demonstration that trypsin-modified F1 cannot bind OSCP indicates that OSCP binds to the alpha subunit of F1 and that F1 contains three binding sites for OSCP. The results are discussed in relation to the possible role of OSCP in the interaction of F1 with the membrane sector of the mitochondrial ATPase system. PMID- 6242248 TI - A protein activator of the plasma membrane Ca++-ATPase of heart sarcolemma. AB - A detergent extract of dog or beef heart sarcolemmal vesicles was prepared and found to have a stimulatory effect on the Ca++-ATPase of plasma membranes from human erythrocyte and cardiac sarcolemma. A procedure is described which enriches the activating fraction. The protein nature of the preparation is illustrated by its sensitivity to boiling and to the proteolytic enzyme(s) trypsin and chymotrypsin. SDS polyacrylamide gels indicate that the protein(s) involved have a molecular weight of 56 and 60 kDa. The sarcolemmal activator can stimulate the Ca++-ATPase activity of the isolated enzyme more than 100% in the presence of saturating amounts of calmodulin. The activation is calcium dependent, being greatest at approximately 10 microns Ca++, free, but does not change the Km for Ca++. A possible physiological role for the activator is discussed. PMID- 6242247 TI - Biogenesis of mitochondria: defective yeast H+-ATPase assembled in the absence of mitochondrial protein synthesis is membrane associated. AB - We have investigated the extent to which the assembly of the cytoplasmically synthesized subunits of the H+-ATPase can proceed in a mtDNA-less (rho degree) strain of yeast, which is not capable of mitochondrial protein synthesis. Three of the membrane sector proteins of the yeast H+-ATPase are synthesized in the mitochondria, and it is important to determine whether the presence of these subunits is essential for the assembly of the imported subunits to the inner mitochondrial membrane. A monoclonal antibody against the cytoplasmically synthesized beta-subunit of the H+-ATPase was used to immunoprecipitate the assembled subunits of the enzyme complex. Our results indicate that the imported subunits of the H+-ATPase can be assembled in this mutant, into a defective complex which could be shown to be associated with the mitochondrial membrane by the analysis of the Arrhenius kinetics of the mutant mitochondrial ATPase activity. PMID- 6242249 TI - Serum hexosaminidase as a possible biomarker for human cancer. AB - The levels of total serum hexosaminidase and of its heat stable isozyme (beta hexosaminidase) were determined in the sera of subjects bearing ovarian and other female genital cancers and of control subjects. The assays were carried out on a double blind basis. Total hexosaminidase levels were significantly elevated in sera of subjects with female genital cancers and in subjects with ovarian cancer. Levels of beta-hexosaminidase were elevated in all subjects with genital cancer. The hexosaminidase assay may be a convenient biomarker for human cancer since earlier studies have shown that total and beta-hexosaminidase levels are elevated in sera of most cancer patients studied. PMID- 6242250 TI - Chromosomal damage induced in human lymphocytes by medroxyprogesterone acetate treatment for precocious puberty. PMID- 6242252 TI - Synthesis and transport of the precursor for the beta-subunit of rat liver F1 ATPase. AB - The synthesis and intracellular transport of the beta-subunit of rat liver F1 ATPase was studied in a cell-free system, using free polysomal mRNA from rat liver and isolated rat hepatocytes. The beta-subunit of rat liver F1-ATPase is synthesized as a larger precursor form in rabbit reticulocyte lysate and then transported into isolated mitochondria in the absence of protein synthesis. In pulse experiments at 37 degrees C, the precursor of the beta-subunit reached a plateau 30 min after the pulse. The labeled mature beta-subunit appeared in the particulate fraction (containing mitochondria) after a time lag and increased almost linearly with time up to 40 min. PMID- 6242251 TI - [Changes in the central and peripheral nervous system in cows after laparotomy]. AB - Two sexually mature cows were used for the studies in which operations were performed, consisting in cutting the abdominal tunics at a length of 30 cm in the left iliac region. The cows were kept alive for 21 days after the operation. Then they were slaughtered, taking the following material for studies: The spinal cord, bilateral spinal ganglions, bilateral subvertebral sympathetic ganglions and autonomous ganglions of abdominal and pelvic cavities. The material was embedded in paraffin and cut into 15 n sections, which were stained with methylene blue according to Nissel. Regressive changes in cells of many nervous centres due to the operations performed were found. They were found in: spinal ganglions of the lumbar and sacral segment, nuclei of spinal grey matter (nucleus motorius, nucleus dorsalis, nucleus intermediomedialis, nucleus intermediolateralis) in the lumbar and sacral segment and in the sympathetic subvertebral ganglions of the lumbar and sacral segment. Degeneration changes of the cells were observed only on the operated side. PMID- 6242253 TI - Treatment of metastatic gastric cancer by combined radiation and hyperthermia (report of two cases). AB - Two patients with metastatic carcinoma of the stomach on the abdominal wall were treated by radiotherapy using cobalt-60 gamma-ray or megavoltage electrons combined with hyperthermia induced with a Thermotron (8 MHz). The total dosage was 44 Gy fractionated into 11 doses (twice a week), by cobalt-60 gamma-ray and 10 hyperthermia treatments for patient 1, and 32 Gy fractionated into eight doses (twice a week) given by megavoltage electrons and five hyperthermia treatments for patient 2. In patient 1, the shrinkage of the tumor was more than 50%. No tumor cells were observed histologically at the end of treatment. In patient 2, the tumors completely disappeared. These results encourage us in the use of radiotherapy combined with hyperthermia for rather radioresistant adenocarcinoma. PMID- 6242254 TI - [Hirsutism secondary to congenital adrenal hyperplasia caused by a 21-hydroxylase deficiency of late onset. A clinical case]. PMID- 6242255 TI - [Clinical, endoscopic and histopathological study in patients with schistosomiasis mansoni]. PMID- 6242256 TI - [Percutaneous transluminal coronary angioplasty (PTCA)]. PMID- 6242257 TI - [National comparative survey on dental care of the handicapped. Results and comment]. PMID- 6242258 TI - [Dental treatment in patients at risk for heart arrythmias: evaluation of the use of Holter electrocardiographic monitoring]. PMID- 6242260 TI - Role of the cervical and lumbar proprioceptors during stepping. An electromyographic study of the muscular activities of the lower limbs. AB - To obtain evidence of the role of the cervical and lumbar proprioceptors during stepping, the following investigations were carried out. 1) 10 normal, healthy subjects and vertiginous patients, particularly those with lumbar pain, were examined. 2) Fukuda's stepping test was first carried out, followed by two modified stepping tests, i.e., stepping after fixing the waist with a corset and after fixing the neck with a collar. 3) Electromyograms (EMGs) of the gastrocnemius muscles of the extensor of the lower limbs were analysed as regards the foot contact with the ground. The following results were obtained. In the original way of Fukuda's stepping test, normal subjects tended to show EMG discharges from the gastrocnemius muscles before foot contact with the ground, whereas in the modified stepping tests, the generation of EMG discharges was delayed, especially in the test requiring fixing of the waist with a corset. The results of these stepping tests were reversed in the vertiginous patients, particularly in those with lumbar pain. We conclude that the lumbar proprioceptors participate especially in the smooth performance of stepping by promoting the anticipatory activity of the extensor of the lower limbs. PMID- 6242259 TI - Beta thalassemia and heart disease: three decades of gradual progress. PMID- 6242261 TI - Insulin binding and degradation in short time incubation at 37 C. AB - Studies on insulin-receptor binding in a short time incubations at 37 C have shown that neither internalization nor receptor-mediated insulin degradation are demonstrable during the first minutes. In the present study insulin receptor binding at 37 C in short time incubation periods was studied in mouse hepatocytes, simultaneously determinating the proportion of degradation due to the cell activity. Degradation in the incubation buffer after cell separation was abolished during the experiment (900 sec) by a careful wash of the cells. 7.5 cells/ml were incubated with a tracer concentration (14.17 pM) of 125I-insulin and a pharmacological concentration (16.6 microM) of native insulin plus tracer. In the case of tracer insulin, 50% binding was reached in 55 sec and steady state in 160 sec. Once reached, steady state persisted along the experimental time. Binding follows a second order kinetics with k+1: 5 649 X 10(6) M-1 sec-1. In the presence of pharmacological insulin there is competitive inhibition of the tracer which reduces to zero the percent of binding. Binding increases along the time taking positive values, and the slope of binding versus time intersects the abscissa at 102 sec (r: 0.864). As long as binding of the tracer takes place, no degradation occurs until 635 sec, when a degradation slope abruptly appears (r: 0.722). Dissociation studies were followed previous incubation at 37 C during 200 sec with tracer and pharmacological doses. Specific dissociation follows a monoexponential kinetics with k-1: 3 067 X 10(-3) sec-1 and t 1/2: 226 sec. Eighty percent of bound insulin is dissociated with no changes in the slope (r: 0.820), thus suggesting that insulin-receptor binding in the present experimental conditions is basically a reversible process. No degradation was observed during dissociation, which demonstrates that insulin-receptor binding does not degrade insulin if internalization is not performed. At steady state, competitive inhibition curves showed two components: high and low affinity. Doses of 1.66 microM produce a 98% inhibition in the binding of 125I-insulin. The high affinity slope shows two components in the physiological range of insulin concentrations. The first one of very high affinity has a dissociation constant Ko: 7 075 X 10( 10), and a binding capacity of 1.5 X 10(-10). This study demonstrates that, with physiological concentrations of insulin, internalization is the only mechanism of insulin degradation in mouse-hepatocytes. PMID- 6242262 TI - Liver cells binding with high insulin doses at 37 C. AB - Insulin binding and receptor mediated insulin degradation were studied in isolated rat hepatocytes under physiological conditions (37 C, 100% oxygen, Krebs improved Ringer III with glutamate, pyruvate and fumarate, 150 mg% glucose, 1% bovine albumin). 10(6) rat hepatocytes/tube were incubated with various doses of insulin. Steady state binding with low insulin doses (0.05, 0.5 and 66 ng/tube) was reached in 15 minutes, that state being kept for the rest of the experimental time (75 min). Receptor mediated degradation (Kap) at 15 minutes was 0.0479 min 1, including doses of 5 000 and 50 000 ng/tube. Direct correlation was found between degradation and low doses of insulin, being the slope value equal to Kap. Intracellular accumulation of insulin was found at pharmacological concentrations of insulin (5 000 and 50 000 ng/tube) from the first 15 minutes. That accumulation was dose and time dependent. At 75 minutes, with a 0.2 microM insulin concentration, at least 53% of insulin was estimated as insulin accumulated in the cell, since it was not filtrable with acid medium on Sephadex G 50 superfine. When Triton or dodecyl sulphate were used to solubilize the cells, insulin recovery was complete after binding. Intracellular accumulation, however, was not demonstrated at the first two minutes. Binding studies with 16.67 microM insulin in the presence of degradation inhibitors, such as 2 mM N ethylmaleimide and 5 mM tetracaine hydrochloride, demonstrated that intracellular accumulation of the hormone occurs when degradation is blocked. On the contrary, after trypsin digestion of receptors, degradation was not observed, while increases in binding were abolished, resembling non-specific binding. Under the experimental conditions reported here, neither intracellular accumulation of insulin nor extracellular release of insulin degradation products can be demonstrated at 2 minutes; insulin accumulation is dose dependent, and it is suggested by the fact that the velocity of insulin internalization exceeds its velocity of degradation. PMID- 6242263 TI - Respiratory changes after intraarterial acetylcholine and abdominal concussion. AB - In 50 dogs anesthetized with chloralose the respiratory changes produced by intraarterial acetylcholine (ACh) and after an abdominal blow, were studied. Intraarterial ACh produced expiratory apnea when it was injected in the superior and inferior mesenteric artery, splenic and left gastric artery. This apnea disappeared when the splanchnic nerves were severed and disappeared or decreased after atropine sulfate was injected. The duration of the apnea coincides with the contraction of the gut smooth muscle recorded, with a small balloon placed in the jejunum or in the ileum. The ACh did not produce respiratory changes when it was injected in the hepatic artery and pulmonary trunk. In the peripheral arteries, especially in the subclavian, ACh injection produced a respiratory stimulation which could be caused by the pain which accompanied the muscular contraction. After a blow in the abdominal wall, an expiratory apnea was also obtained, similar to that observed by the injection of ACh in the gastrointestinal arteries. This apnea disappeared when splanchnic nerves were severed or when atropine sulfate was injected. Smooth muscle contraction was also observed, suggesting that the expiratory apnea was originated in the smooth muscle receptors. PMID- 6242264 TI - [Experimental porphyria induced by chlorinated hydrocarbons. Studies of porphyrinogen carboxy-lyase in the experimental model of human cutaneous delayed porphyria]. AB - The present work tries to elucidate if the strong decrease of porphyrinogen carboxy-lyase (PCL) observed in the experimental porphyria caused by hexachlorobenzene (HCB) is due to the presence of an inhibitor or to a modification of the protein structure of the enzyme. For this purpose: a) cross assays and heating ones were performed in order to look for the existence of a compound, that present in porphyric animals, would be responsible for the decrease of PCL activity found in them; b) the effect in vitro of HCB, HCB metabolites and other related compounds was studied to find the inhibitor of PCL activity and to look for a relation structure-inhibitory effect; c) hepatic PCL from porphyric and normal rats was purified, and enzyme properties were comparatively studied looking for structural differences between the enzymes obtained from both animal lots. The results indicate that: a) the heat deproteinized porphyric liver preparation produces an inhibition on the normal preparation, but it is smaller than the decrease produced in vivo by the HCB on this enzyme activity, thus other reasons may explain this behavior of PCL in intoxicated animals; b) the HCB had no effect on PCL activity, the phenolic compounds exhibited inhibitions of variable extent that were increased by the presence of electrophilic substituents on the benzenic ring. Pentachlorophenol, the main HCB metabolite, produced inhibition in the in vitro assays, but at doses that were not physiologically significant; thus, it seems not to be the inhibitor found in the heating assays; c) purification of 110 times for the hepatic PCL of both porphyric and normal rats was obtained. Incubation conditions, the effect of salts and chelating agents, the chromatographic behavior in DEAE-cellulose and Sephadex G-100 columns, were comparatively studied with both enzymatic preparations. The effect of sodium diethyldithiocarbamate, sodium pyrophosphate, dithiothreitol, temperature, pH and O2, as well as the chromatographic behavior, would suggest that structural differences in the PCL of porphyric animals may exist; the presence of a thermostable inhibitor could also contribute to the decrease of PCL activity due to HCB. PMID- 6242265 TI - Increase in transmitter release from motor nerve terminals induced by some pyridine derivatives. AB - The effects of 4-nitropyridine (4-NP), 4-aminopyridine-N-oxide (4-AP-N-O), 4 hydroxypyridine (4-HP), 2,6-diaminopyridine (2,6-DAP), 2,4-dihydroxypyridine (2,4 DHP) and pyridine on isolated sciatic nerve-sartorius muscle preparations were studied by means of intracellular and extracellular recording techniques. In junctions treated with (+) tubocurarine, 4-NP, 4-AP-N-O, 4-HP and 2,6-DAP reversibly increased the amplitude and the latency of end-plate potentials (EPPs) and induced repetitive EPPs in response to single nerve impulses. As shown by extracellular focal recordings, the increase in latency of EPPs was due to a prolongation of the minimum synaptic delay, while the appearance of repetitive EPPs was the result of repetitive firing of motor nerve terminals. 4-NP, 4-AP-N O, 4-HP and 2,6-DAP increased dose-dependently the quantal content of EPPs, while 2,4-DHP and pyridine were found to be inactive. Comparison of the apparent rank order of potency in increasing quantal transmitter release indicates that the relative activity of the different pyridine derivatives studied is unrelated to their pK values. Spontaneous quantal transmitter release in resting junctions was unaffected by 4-NP, 4-AP-N-O, 4-HP and 2,6-DAP when applied at concentrations that enhanced evoked transmitter release. 4-NP differed from the other pyridine derivatives by producing in high concentrations a time-dependent increase in miniature end-plate potential frequency and a depolarization of the muscle fibres. In addition, 4-AP-N-O, 4-HP and 2,6-DAP were found to have no effect on MEPP frequency accelerated by increasing the external K+ concentration. In conclusion the data presented strongly suggest that 4-NP, 4-HP, 4-AP-N-O and 2,6 DAP facilitate evoked transmitter release from motor nerve terminals by a presynaptic action that seems related to an increased calcium influx secondary to the blockade of potassium channels in the nerve terminal. PMID- 6242266 TI - Insulin processing. Its correlation with glucose conversion to CO2. AB - Insulin-receptor binding, insulin degradation and biologic response (14C-glucose conversion into 14CO2) were studied in adipocytes of control (CG), fasted (FG-88 hr) and hyperinsulinic rats (HG-exogenous hyperinsulinism). The number of cells normalized to 3.5 X 10(5) cells/tube in all three groups. Insulin binding and degradation were studied at 5, 15, 30, 60 and 120 minutes of incubation with 3.5 X 10(-11) M, 6.66 X 10(-11) M, 1.0 X 10(-9) M, 6.66 X 10(-9) and 6.66 X 10(-6) M insulin. The net increments of 14CO2 taken into account (delta U-14C-glucose converted into 14CO2) ranged from the basal value to 10(6) microU in each case (30, 60 and 120 minutes). Quantitative analysis of results was performed with the Terris and Steiner degradation equation (formula; see text) (IR). Differences in insulin binding, comparing the three groups, lacked statistical significance, though FG data were systematically plotted above those of CG, occurring the opposite with HG. Degradation studies showed HG to have values statistically higher than the controls, while FG values were lower. HG also showed higher amounts of 14CO2, with basal levels more elevated than CG, while FG showed the inverse behavior. 14CO2 increased in the three groups along the 120-minutes incubation period (30, 60 and 120 minutes). Receptor-mediated degradation at 30 minutes, when binding is in steady state, showed a Kap value very close to that found by linear regression for the 2 and 10 microU doses (Kap min-1 CG: 0.1654, FG: 0.0824, HG: 0.5045; slope values for the 2 and 10 microU doses CG: 0.2181, FG: 0.0824, HG: 0.3718). The degradation velocity, considered as function of IR, was constant in each group at 30, 60 and 120 minutes. Since Kap values in the FG and HG indicate differences in their degradation velocities, this constant can be considered as indicative of the metabolic situations under study. At the same time, the biologic response (14C-glucose conversion into 14CO2) depends as well on the metabolic conditions. Glucose consumption and Kap value were then compared. All the groups showed linear correlation between the binding dependent velocity of degradation (Kap) and the net conversion of U-14C-glucose into 14CO2 at 30, 60 and 120 minutes, with ordinate close to zero (30 min: 0.1539; 60 min: 0.3812; 120 min: 0.1311). The slope increased along the incubation period, indicating that 14CO2 accumulation is time dependent.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 6242267 TI - [Argentinian Association of Experimental Pharmacology. 25th annual meeting. Abstracts of scientific communications. La Falda, Cordoba, 2-5 November 1983]. PMID- 6242268 TI - Chalones and specific growth factors in normal and tumor growth. PMID- 6242269 TI - [A case of percutaneous transluminal angioplasty of renovascular hypertension in a solitary kidney]. AB - The patient was a 18-year-old woman. Past history included right nephrectomy for right congenital hydronephrosis when she was an infant of 40 days. On examination, her blood pressure was 220/140 mmHg, and plasma renin activity was 4.2 ng/ml/hr. The selective renal arteriogram showed fibromuscular dysplasia of the left main renal artery, and a diagnosis of renovascular hypertension in the solitary kidney with an aberrant artery was made. Treatment with orally-active inhibitor of angiotensin I converting enzyme, Captopril, was started. Her blood pressure became normal after oral administration of Captopril, but her renal function deteriorated. Therefore, percutaneous transluminal angioplasty was performed twice resulting in effective dilatation of the stenotic portion of the left main renal artery. Thereafter, her blood pressure fluctuated between 170/120 and 140/70 mmHg. Eight months later, her blood pressure is now being controlled with mild antihypertensive treatment. PMID- 6242270 TI - Nutritive value of slaughter by-product meals. PMID- 6242271 TI - Efficacy of lasalocid sodium against mycoplasmas (preliminary communication). PMID- 6242272 TI - Correlations between the titres of natural and immune antibodies to sheep erythrocytes in inbred mouse strains. PMID- 6242273 TI - Sexual dimorphism of long bone growth in cattle. PMID- 6242275 TI - Occurrence of new monogeneans of Far-East origin on the gills of fishes in Hungary. PMID- 6242274 TI - Production of T-2 toxin and related trichothecenes on different media. PMID- 6242276 TI - Fine structure of the process of oocyst wall formation of Eimeria maxima (Apicomplexa: Eimeriina). PMID- 6242277 TI - Effect of pH and temperature on four dehydrogenase enzymes of Haemonchus contortus. PMID- 6242278 TI - Effect of thyrotropin (TSH) treatment on the vitamins A and E and lipid-peroxide status of domestic fowl. PMID- 6242279 TI - Occurrence and some characteristics of the IgG receptors of the small intestinal mucosa: in vitro experiments. PMID- 6242280 TI - Studies on the availability, transport and utilization of oxygen in low- and high flow septic shock in calves. PMID- 6242281 TI - Effect of periparturient lipid mobilization on serum total carotene and vitamin A concentrations in cattle. PMID- 6242282 TI - Study of the mutagenic effect of Redentin on various species of animals. PMID- 6242283 TI - Acute infusion of hCG and thyroid hormone pattern before and after bilateral orchiectomy. AB - An acute infusion of 5000 IU of hCG was given to a group of 10 elderly men affected by prostatic carcinoma prior to and 1 month after castration to evaluate the possibility of any aspecific effect on thyroid hormones. No significant change was documented for TT4 and TT3, and a significant increase in fT4 occurred only in the presurgical experiment. From these results the authors conclude that the thyroid movement documented may be correlated to the decreased binding capacity of thyroxine-binding globulins promoted by the increase in Te levels. PMID- 6242284 TI - [Current assistance and rehabilitative trends, in dentistry, for individuals with handicaps]. PMID- 6242285 TI - Multiple phenotypic divergence of mammary adenocarcinoma cell clones. II. Sensitivity to radiation, hyperthermia and FUdR. AB - We have shown that, with in vitro passage, subclones derived from clonal cell populations of 13762NF mammary adenocarcinoma undergo phenotypic drift and diversification in their cellular properties. Here we examine whether phenotypic divergence of 13762NF cell clones extends to therapeutic treatments used in eliminating mammary tumors and whether the apparent rates of phenotypic divergence vary for different treatments. Six subclones isolated from low passage clone MTF7 (T11; tissue culture passage 11) cells were compared to a similar number of subclones isolated from high passage clone MTF7 (T35; tissue culture passage 35) cells. Subclones derived from clone MTF7 (T11) were relatively homogeneous (not significantly different) in their inherent sensitivities to ionizing radiation, extrapolation coefficients and quasithreshold dose values (Do = 1.61-1.99 Gy; n = 0.89-3.42; Dq = 0-2.34). When the MTF7 (T11) subclones were examined for their sensitivities to 45 degrees C hyperthermic treatment, the inherent sensitivities and dose-response curve parameters (Do = 5.24-10.05 min; n = 1.08-10.47; Dq = 0.78-12.31) were heterogeneous (significantly different). In addition, the MTF7 (T11) subclones were heterogeneous (significantly different) in their sensitivities and dose-response curve parameters to 5-fluoro-2' deoxyuridine (FUdR) treatment (slope = -0.70 to -1.59; y-intercept = 1.31 X 10(2) to 47.80 X 10(2]. The LD50 values for FUdR ranged from 14-150 nM for the MTF7 (T11) subclones. At high passage MTF7 (T35) subclones were heterogeneous in their dose-response parameters to ionizing radiation (Do = 1.17-2.05 Gy; n = 0.80 41.18; Dq = 1.79-4.94), hyperthermia (Do = 3.57-6.32 min; n = 2.08-13.54; Dq = 3.68-9.30) and FUdR (slope = -0.77 to -0.93; y-intercept = 4.64 X 10(2) to 8.83 X 10(2); LD50 = 50-160 nM). The results indicate that clonal cells diverge for distinct phenotypic properties at differing rates to form heterogeneous cell populations with unique sensitivities to various therapeutic treatments. PMID- 6242286 TI - [2-year clinical studies after application of Nuva-Seal sealing material]. PMID- 6242287 TI - Effects of nicotinamide on cardiac A-V conduction and function of sinus node in isolated hearts. PMID- 6242288 TI - M-mode echocardiographic features of children with Keshan disease. A preliminary observation of 106 cases. PMID- 6242289 TI - The metabolism of pyrimidine and purine in Schistosoma japonicum. PMID- 6242290 TI - [A preliminary report on hepatic artery embolization in the treatment of primary liver cancer]. PMID- 6242291 TI - [Some problems concerning the histological diagnosis of gliomas of the brain by CT scan]. PMID- 6242292 TI - [CT diagnosis of acoustic tumor]. PMID- 6242293 TI - [Percutaneous puncture biopsy of the lung (report of 100 cases)]. PMID- 6242294 TI - [Roentgen diagnosis of gastric volvulus (an analysis of 98 cases)]. PMID- 6242295 TI - [Roentgen diagnosis of gastric linear ulcers]. PMID- 6242296 TI - [Postoperative roentgen studies of 127 cases of congenital hypertrophic pyloric stenosis]. PMID- 6242297 TI - [The cocooned small intestine (report of 3 cases)]. PMID- 6242298 TI - [Plain film and tomographic study of the sella turcica in 100 cases of gigantism and acromegaly]. PMID- 6242299 TI - [Diffuse idiopathic skeletal hyperostosis (DISH) with X-ray analysis of 30 cases]. PMID- 6242300 TI - [Roentgen study of the skeletal system in Kaschin-Beck disease]. PMID- 6242301 TI - [X-ray manifestations of the bone in myxedematous endemic cretinism]. PMID- 6242302 TI - [Ossifying fibroma of the long bones (report of 14 cases)]. PMID- 6242303 TI - [Primary benign chondroid tumor of soft tissue with review of the literature and report of two cases]. PMID- 6242305 TI - [Quantitative and qualitative analysis of radiographic magnification]. PMID- 6242304 TI - [An analysis of the treatment of Cushing's disease by 60-cobalt (73 cases)]. PMID- 6242306 TI - [Management of radiographic technics]. PMID- 6242307 TI - [Clinical applications of x-ray tomography]. PMID- 6242308 TI - [Preliminary study of the determination of T gamma and T mu cells in the peripheral blood in oral and maxillofacial carcinomas]. PMID- 6242309 TI - [Immunologic function disorder in tuberculosis]. PMID- 6242310 TI - [Continuous measurement of cardiac output during ergometer exercise using an ultrasonic pulsed Doppler flowmeter]. AB - A method for determining cardiac output was developed, which provided the product of the absolute blood flow rate at the aortic arch (as measured non-invasively from the suprasternal notch by an ultrasonic pulsed Doppler flowmeter: UPDF) and the cross-sectional area of the aorta at that level, as estimated from two dimensional echograms. Using this method, non-invasive continuous measurements of cardiac output were made during bicycle ergometer exercise. The results were summarized as follows: Resting cardiac output values obtained by this method correlated reasonably well with those by the thermodilution method (correlation coefficient r = 0.76). Eight healthy male volunteers exercised for 2 min on a bicycle ergometer at 250 kpm/min, and serial cardiac outputs were determined by this method for five of these subjects during and after the loading. The cardiac output curves thus obtained clearly demonstrated abrupt increases in cardiac outputs initially, followed by rapid returns to resting cardiac output levels after the end of exercise. We intend to conduct additional studies for larger groups of subjects to further evaluate and to establish this method for use in cardiac examinations. PMID- 6242311 TI - Hepatitis B: another look at prevaccination screening. PMID- 6242312 TI - Characterization of rabbit masseter muscle fibers. AB - Myosins of histochemically distinguishable single fibers of rabbit masseter muscle--type 1, 2A, 2B, and slow fibers--have been characterized by gel electrophoresis under dissociating (sodium dodecyl sulfate) and nondissociating (inorganic pyrophosphate) conditions, and by analysis of peptide maps of the heavy chains following limited proteolytic degradation. Type 2B fibers contain more LC3 homodimer than type 2A fibers; peptide maps of their heavy chain are different although the two myosins comigrate on pyrophosphate gel electrophoresis. Slow fiber myosin migrates more slowly than fast myosin and has a distinct peptide map. Differences were also found among fibers of the same histochemical type but originating in different muscles. In adductor magnus 2B myosin the LC1 + LC3 heterodimer band is the strongest, while in masseter 2B myosin the heterodimer is the weakest. Statistical considerations suggest that in masseter there is a mechanism preferentially forming the homodimers. More work is needed to determine the mechanism by which phenotypical differences occur among various fiber types in the same muscle and between corresponding fiber types in different muscles. PMID- 6242313 TI - Brominated vegetable oil myopathy: inhibition at multiple sites. AB - Skeletal muscle lipid storage was induced by feeding rats brominated vegetable oil (BVO). The defect was examined by measuring radioactive substrate oxidation, intermediates of fatty acid oxidation, and activities of oxidative enzymes. One- and U-[14C] palmitate and 1-[14C] pyruvate oxidation were reduced in muscle after four doses of BVO. Inhibition of U-[14C] palmitate oxidation occurred after two doses. Short chain acylcoenzyme A(CoA) derivatives accumulated in the muscle. Several enzymes of beta-oxidation were significantly reduced, with the greatest reduction in 3-ketoacyl-CoA thiolase. The inhibition probably affected multiple sites of CoA and CoA-derivative metabolism. PMID- 6242314 TI - The interaction of unregulated actin and myosin in avian muscular dystrophy. AB - The presence of an altered form of the heavy chain component of myosin subfragment-1 (S-1) in avian dystrophic pectoral muscle was confirmed by Triton urea-acetic acid polyacrylamide gel electrophoresis. The potential functional significance of this altered form of S-1 was evaluated by measuring the ATPase activity of the unregulated acto-S-1 complex using all possible pairwise combinations of actin and S-1 from normal (N) and dystrophic (D) muscle. (NN, DD, ND, DN, where the first letter designates the actin and the second letter the S 1). With conventionally purified actin and S-1, NN not equal to DD not equal to ND not equal to DN, implying both N actin not equal to D actin and N S-1 not equal to D S-1 functionally. An alternate purification scheme for actin resulted in preparations from normal and dystrophic muscles of actin Mg-polymers with the same rheology (viscosity vs shear rate) and critical concentration for polymerization. When these actins were combined with more highly purified preparations of S-1, the adenosine triphosphatase (ATPase) activity of the acto-S 1 complex did not vary with changes in the pairwise composition and responded similarly to variation of the actin or adenosine triphosphate (ATP) concentration. In experiments with actin activation of intact myosin, no differences were observed between myosin from normal vs dystrophic muscle. The different isozymes of myosin present in normal and dystrophic chicken pectoral muscles are functionally equivalent as ATPases in their interactions with unregulated actin. PMID- 6242315 TI - Thromboscintigraphy with 99Tcm-plasmin: a new diagnostic method in deep venous thrombosis of the legs. PMID- 6242316 TI - [Aorto-arteriography of the limbs after transcutaneous puncture of vascular prosthesis made of a plastic material. The technic and safety of the procedure]. PMID- 6242317 TI - [Hepatitis B and professional groups with high risks of exposure]. PMID- 6242318 TI - [Dental changes in children with Down's syndrome]. PMID- 6242319 TI - [New dentin adhesives and their clinical application]. PMID- 6242320 TI - [Immunotherapy of malignant tumors with subpopulations of T lymphocytes]. AB - During tumor growth specific suppressor cells and non-specific macrophages increase, while helper T cells decrease, preventing the production of an adequate immunological reaction. This immunosuppression can be subdued transferring specific helper cells, that contribute to the production of effector cytotoxic lymphocytes, cooperate with B lymphocytes to produce anti-tumor antibodies, and induce the accumulation of macrophages, lymphocytes, null cells and granulocytes in the tumor zone. The experiments have been done with sarcomas induced in the BN rat by Moloney virus and methylcholanthrene, respectively. It is possible that the experimental model may be applied to human tumors. PMID- 6242321 TI - The physiology of phytochrome action. PMID- 6242322 TI - A possible role for Ca2+ in mediating phytochrome responses. PMID- 6242323 TI - On the mechanism of ATP synthesis in oxidative phosphorylation. PMID- 6242324 TI - Membrane ATPase activation on infection of E. coli K (lambda) cells with phage T4rII mutants. PMID- 6242325 TI - Photophysiological functions of visual pigments. AB - In order to gain a fundamental understanding of functions of a visual pigment, i.e., photoreception and phototransduction, it is essential to elucidate the molecular structure of visual pigment, its photochemical behavior and connection of the pigment to the molecular physiological amplification mechanism for excitation of a visual cell. A rhodopsin, a rod visual pigment, is composed of an 11-cis-retinal bound with an apo-protein, opsin, through a protonated Schiff base. Competitive inhibition of beta-ionone on regeneration of rhodopsin from an 11-cis-retinal and cattle opsin demonstrated the existence of a hydrophobic linkage between the beta-ionone ring of the retinal and the hydrophobic region of opsin. Owing to these two linkages, the 11-cis-retinal is fixed in an opsin cleft. As a result, it is endowed with new physiological functions as a chromophore of rhodopsin; the change of 11-cis-retinal (lambda max = 369 nm, epsilon = 26,400) to rhodopsin (lambda max = about 500 nm, epsilon = 40,600) brings not only a spectral shift from near ultraviolet to visible regions and an intensification of the molecular extinction coefficient, but also an increase of a quantum yield of 11-cis-retinal to all-trans form. High quantum yield of rhodopsin suggests rapid formation of the first photoproduct. Study of the first photoproduct was accelerated by the finding of bathorhodopsin, which was formed by irradiation at liquid nitrogen temperatures. The change of rhodopsin to bathorhodopsin has been inferred to be due to a photoisomerization of the chromophore from 11-cis to a twisted all-trans form. This isomerization hypothesis has been verified by the following experimental results. Irradiation of 7-cis- and 9-cis-rhodopsins at liquid nitrogen temperature produced the same bathorhodopsin as that from 11-cis-rhodopsin, indicating that the chromophore of bathorhodopsin should be in all-trans or transoid form. 7-Membered-rhodopsin, in which the rotation of 11-12 double bond of the retinylidene chromophore is locked, did not form bathorhodopsin by excitation of picosecond laser photolysis. This fact indicates that bathorhodopsin is a product formed by photoisomerization of the chromophore. Rhodopsin showed a positive circular dichroism (CD) in the visible while bathorhodopsin showed a remarkable negative CD. The reversal of the sign of CD indicates that not only large conformational change of the retinylidene chromophore occurs during the conversion of rhodopsin to bathorhodopsin, but also the direction of twist of the chromophore reverses. It is inferred that the chromophore of bathorhodopsin is a twisted trans form.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 6242326 TI - Role of subunit interactions in the self-assembly of oligomeric proteins. AB - In oligomeric proteins, the native conformation and its functional properties depend on the interactions which exist between the different chains. The role of these subunit interactions can be studied using either the unfolded state or the native state as a starting point. During the folding process, the properties which appear following a bimolecular reaction are related to the formation of an association area. Similarly, the properties which are lost upon partial dissociation of the native state are related to the association area which is disrupted. Four examples are presented in this article: phosphofructokinase and aspartokinase-homoserine dehydrogenase from E. coli are studied through their folding process, and fatty acid synthetase from B. ammoniagenes and reptilian ovomacroglobulin are studied through their dissociated forms. In all cases, the function of the protein is a sensitive index of the formation of the subunit interactions, and can be more conveniently measured than other size/shape parameters. The extrapolation from the folding of small proteins to the assembly of large and complex structures can be reasonably achieved by admitting that subunit interactions are coupled to the subtle adjustments required by the protein to exert its biological function. PMID- 6242327 TI - Cytophysiological studies on the effects of amphenone 'B' and dexamethasone on the pars distalis and interrenal gland of Rana cyanophlyctis (Schn.). AB - Amphenone 'B' treatment resulted in the hypertrophy and degranulation of the B3 cells of the pars distalis and stimulation of interrenal cells, whereas administration of dexamethasone caused regression of B3 and interrenal cells. Following 15-day cessation of amphenone or dexamethasone treatment, there was no recovery in the B3 or the interrenal cells. The results suggest that B3 cells are the probable source of ACTH and there exists a relationship between the pituitary and interrenal gland of the frog, R. cyanophlyctis. PMID- 6242328 TI - The autologous mixed lymphocyte reaction: a basic immune regulatory mechanism. International workshop, Erlangen, West Germany, October 14 and 15, 1982. PMID- 6242329 TI - Cellular interactions in the human T-T autologous mixed lymphocyte reaction. AB - Human peripheral blood T cells and T cell subsets were studied for the proliferative response in the autologous mixed lymphocyte reaction (AMLR) upon stimulation with mitogen- or AMLR-activated T cells and T cell subsets. T cells exhibited a vigorous proliferative response when stimulated with autologous activated T cells but not with unactivated T cells. The stimulatory capacity of activated T cells in the T-T AMLR was inhibited by prior treatment with 7.2 anti DR monoclonal antibody in the absence of complement A BUdR and light experiment clearly demonstrated that T cells responding to activated T cells in the AMLR were distinct from those responding in allogeneic MLR. Further analysis with OKT4+ and OKT8+ T cell subsets demonstrated that OKT8+ T cells were the major responder upon stimulation with PHA-activated T cells. In contrast, OKT4+ T cells were the major responder in the T-T AMLR, when AMLR-activated T-cells were used as stimulators. T cells activated in T-T AMLR (PHA-activated T cells as stimulators) demonstrated suppressor activity against the proliferative response of autologous responder T cells. This study demonstrates that distinct subsets of T cells respond in the T-T AMLR and express suppressor activity. PMID- 6242331 TI - Fetal calf serum augmentation during cell separation procedures accounts for the majority of human autologous mixed leukocyte reactivity. AB - In the present experiments, we have observed that cells separated using techniques that provide no xenoantigen exposure to stimulator cells do not participate in the autologous MLR. However, exposure of separated cells in general and stimulator cells in particular to fetal calf serum does lead to autologous MLR. These data confirm the previous observations of Huber et al. that the human autologous MLR is primarily due to xenoproteins absorbed to stimulating cells during the separation procedures and indicate that a reassessment of human autologous MLR studies will be needed. PMID- 6242330 TI - Role of B cells in the stimulation of syngeneic mixed lymphocyte responses. AB - Two different approaches were used to examine the role of B cells in the stimulation of syngeneic MLR. The relative inability of spleen and peritoneal exudate cells from B cell deficient mice, treated with anti-mu from birth, to serve as stimulator cells in SMLR was previously shown in SJL mice and confirmed in BALB/c mice in the present studies. Preincubation of cells from anti-mu treated mice with serum Ig does not enhance their ability to stimulate. Upon stimulation with normal spleen cells responses from anti-mu treated mouse T cells are not deficient. Responses of thymus cells from neonates and from adult cortisone-treated mice are also much higher when the splenic stimulator cells come from normal rather than from anti-mu treated mice. The deficiency of the stimulator cells from anti-mu treated mice is in the high density cell population as obtained after BSA gradient fractionation of collagenase treated lymph node or spleen fragments. Low density populations from anti-mu treated and normal mice stimulate equally well. Addition of exogenous IL-2 to the cultures enhances the syngeneic MLR to all stimulator populations and allows stimulation by spleen cells from anti-mu treated mice. It is concluded that, while B cells represent the major stimulator cell population in whole spleen cell suspensions, other accessory cells (dendritic cells?) are more efficient, possibly synergize with B cells by producing IL-1, but usually represent only a minor subpopulation. The other approach concerns the effectiveness of SMLR stimulation by several tissue culture, cloned B lymphoma cell lines, and by a transplantable BALB/c B lymphoma. Of the five stimulating lymphoma cell lines only one stimulates approximately as well in the absence as in the presence of polyethylene glycol. These latter cells (A20.1.11) can also stimulate T cell proliferation and IL-2 production in the absence of Ia+ accessory cells in the responding population and, therefore, either produce their own IL-1 or are able to bypass the requirement for this lymphokine. PMID- 6242332 TI - Responder cells in the human autologous mixed lymphocyte reaction (AMLR). Characterization and interactions in healthy individuals and patients with systemic lupus erythematosus. AB - In the course of a primary AMLR, purified T4 cells, but not purified T8 cells, proliferate to the non-T cell stimuli; however, in the presence of T4 cells or helper factors secreted by T4 cells, also T8 lymphocytes are able to proliferate in the AMLR. These observations together with findings on immunoregulatory capacities of AMLR-activated T cells suggest that the AMLR represents a model inducer circuit. In patients with SLE, our preliminary data indicate a deficient response of T4 cells upon stimulation with non-T cells. In addition, in occasional patients activation of T8 lymphocytes may be defective as well. In one patient with a low T4/T8 ratio, elimination of excess T8 cells increased the AMLR dramatically when compared to unfractionated T cells. Thus, the AMLR using unfractionated T cells may not necessarily represent the intrinsic capacity of SLE T cells to respond to the non-T stimulus. Our data suggest that immune regulation in SLE is deficient on the inducer cell level; moreover, individual patients may have additional abnormalities, supporting the concept of the heterogeneity of SLE. PMID- 6242333 TI - The magnitude of the autologous mixed lymphocyte reaction itself is regulated. PMID- 6242334 TI - Impaired AMLR in autoimmunity. AB - A defective AMLR and impaired production and response to Interleukin 2 (IL-2) occur as a common feature of disease in several autoimmune-susceptible strains of mice and in patients with various autoimmune and lymphoproliferative disorders. We have studied the functional significance of these abnormalities and the cellular mechanism responsible by measuring specific antigen-induced proliferation following in vivo immunization with TNP25-KLH in three autoimmune strains bearing the lpr gene. The lpr mice manifest a decreased response in this assay system. Mixing experiments, in which T cells and macrophages from lpr mice and their normal congenic partners are allowed to interact, demonstrate that the defect resides with the responding Lyt 1+ T cells and not with lpr antigen presenting macrophages. Flow cytofluorometry analysis using monoclonal antibodies to Thy 1.2, Lyt 1 and Lyt 2 reveals an abnormal distribution of these T cells reflecting a low antigen density on the cell surface. The actual number of Lyt 1+ cells is not diminished, but the pattern is displaced. These results suggest that the decreased AMLR, decreased IL-2 production, and decreased antigen-induced proliferation are not due to deficient numbers of responding cells but rather to functional impairment. PMID- 6242335 TI - Immunoregulatory aspects of in vivo syngeneic mixed lymphocyte reactions. AB - In vivo manifestations of two types of murine syngeneic MLR have been described. For the first, neonatal thymic cells that normally replicate in the presence of lymphoid non-T cells were observed to induce splenomegaly 4 days after injection into x-irradiated adult mice. The second instance of S-MLR occurring in vivo involves the induction of suppressor cells in popliteal lymph nodes that drain the site of deposition of syngeneic splenic cells. The suppressor cells were seen to be capable of inhibiting formation of CTLs to allogeneic or hapten-modified syngeneic lymphoid cell targets. The suppressor cells were seen to appear within 3 days and to remain detectable at 7 days following injection of the spleen cells. Whole spleen cell populations as well as nylon wool adherent and non adherent subpopulations were equally competent to induce suppression. Adult thymus cells were less able and lymph node cells as well as haptenated spleen cells were unable to trigger suppression. The possible site of action of the suppressor cells upon the CTL system has been discussed. PMID- 6242336 TI - Studies on the autologous MLR in primary biliary cirrhosis: evidence that the autologous MLR is a negative feedblock response stimulated by activated B cells. AB - Patients with primary biliary cirrhosis (PBC) were found to have diminished suppression of pokeweed mitogen (PWM)-stimulated immunoglobulin synthesis by in vitro cultures containing autologous T and B cells. The possibility that this abnormality is due to a defect of autologous cell-cell interactions was suggested by the finding that patients with PBC have a significantly diminished proliferative response in the autologous mixed lymphocyte reaction (MLR). In studies of normal lymphocytes, it was found that T cells activated in the autologous MLR have the capacity to suppress PWM-stimulated immunoglobulin synthesis, but do not have augmented helper function. Furthermore, when T cells were activated with lymphoblastoid B cells, augmented suppressor activity was observed. These findings suggest that the autologous MLR represents a negative feedback loop in which activated B cells initiate a suppressor T cell pathway. The defect in the autologous MLR in patients with PBC may account for the diminished suppressor cell function observed in this disease. PMID- 6242337 TI - Autologous mixed lymphocyte reactions in rheumatoid arthritis. Characterization of stimulator cells and the recognition unit for autoantigens on the responder cells. AB - Reduced lymphocyte responses were detected in the peripheral blood (PB) of patients with rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA) in the autologous mixed lymphocyte reaction (AMLR) using irradiated non-T cells as stimulator cells and T cells as responder cells. The AMLR responses of synovial tissue (ST) and of synovial fluid (SF) lymphocytes were normal. Dendritic cells both from the peripheral blood (PB), ST and SF were very potent stimulators in the AMLR and in vivo activated, HLA-DR positive T cells both from ST and SF were able to stimulate autologous PB T-cells in both RA and JRA patients. A rabbit antiserum produced against a fragment comprising the variable heavy (VH) chain region of an IgG3 human myeloma protein (Kup) reacted with peripheral blood T cells and inhibited the AMLR responses. Thus, VH antigens are integral parts of the T cell receptor for autologous HLA-DR (Ia) antigens. PMID- 6242338 TI - Ontogenic aspects of the syngeneic mixed leukocyte reaction. PMID- 6242339 TI - Mechanisms of help and suppression in the AMLR: studies in normal and NZB mice. PMID- 6242340 TI - T cell clones and hybridomas as probes for the analysis of the syngeneic mixed leukocyte reaction. AB - We have prepared short term T cell lines, long term T cell lines from soft agar colonies, and SMLR specific T cell hybridomas. Analysis of these populations has shown that the SMLR responsive T cell population is not specific for a foreign serum component, but rather represents a T cell population which can be polyclonally activated by self-Ia antigens. It is likely that some antigen specific cells are found within this autoreactive subpopulation. PMID- 6242341 TI - Analysis of interleukin 2 receptor sites on activated T cells. AB - Earlier work has shown that upon polyclonal or antigen-specific activation murine T cells become susceptable to the affect of the T helper cell product Interleukin 2 (IL-2) leading to clonal expansion of activated T cells. It has been suggested that T-cells, as a result of mitogenic or antigenic triggering, express on their surface receptor sites for IL-2. The aim of the present investigation was to analyse the putative IL-2 receptors by quantitative absorption studies. The following results were obtained: activated T cells, triggered by cell antigen or Con A as well as cells of a CTL-clone, but neither LPS-activated B cells nor tumour cells absorbed IL-2; IL-2 was absorbed in a doses dependent fashion until saturation of the absorbing cells; IL-2 absorption occurred within minutes and was temperature-dependent; data comparing activated T cells versus gluteraldehyde treated activated T cells in repeating absorptions suggested that with gluteraldehyde-treated cells only absorption of IL-2 by the exposed IL-2 receptors is measured, while metabolically active cells seem to assay, besides of the mere binding of IL-2, also an enzymatic event, which probably follows binding of IL-2 to its receptor. The capacity to absorb IL-2 was trypsin-sensitive but insensitive to treatment with neuraminidase. PMID- 6242342 TI - The developmental biology of the syngeneic mixed lymphocyte reaction. AB - The syngeneic mixed lymphocyte reaction (SMLR) is the proliferative response of T lymphocytes cultured with non-T lymphocytes. Normal mouse serum supports proliferative activity in the SMLR comparable to levels observed when fetal calf serum is used. Thus, the SMLR does not appear to be a response to xenogeneic antigens. The ontogeny and senescence of the SMLR was also studied. The SMLR is impaired in mice less than 4 weeks of age but attains adult levels of activity at 4 weeks of age. The SMLR is also impaired in 24-month-old mice. These impairments were observed regardless of the source of serum used in the cultures. Finally, monoclonal antibodies have been developed which identify a subpopulation of spleen cells which respond in the SMLR. In indirect immunofluorescence these antibodies stain 50-80% of cells activated in the SMLR, but only 5-8% of spleen cells or cells activated in the allogeneic MLR. These antibodies block the proliferative response in the SMLR but do not interfere with the response to alloantigens or PHA. PMID- 6242343 TI - Analysis of lymphokine producing T helper cells at the clonal level. AB - The quantitative representation of alloreactive helper T lymphocytes (HTL) within murine Lyt 1+2- cells has been analysed by the limiting dilution approach. Using three different experimental protocols evidence is presented that the HTL limiting the overall generation of both T help and IL-2 production may be distinct from the actual HTL providing T help or producing IL-2. While the former most likely represents the T inducer cell occurring at a frequency of about 1/2000 within Lyt 1/2- cells, the frequency of the latter is estimated to be about 1/200-1/500. PMID- 6242344 TI - Characterization of cytotoxic cells generated in the autologous mixed lymphocyte reaction. PMID- 6242345 TI - Autologous reactive T cell clones and T-T hybrids. PMID- 6242346 TI - Autorosette forming cells: phenotypic analysis, specificity and role in the autologous mixed lymphocyte reaction. AB - The phenotype of autorosette forming cells (A-RFC) in the peripheral blood of normal subjects was analyzed. Using a fluorescent technique in which the rosetting cells are labeled with different monoclonal antibodies directed against various cell surface antigens, we demonstrated that A-RFC are T cells, the majority of which belong to the helper/inducer subset. Nevertheless, about 10% of the A-RFC bear the Leu 2a antigens, which are specific for cytotoxic/suppressor T cells. On the other hand, no autorosettes were identified by OKT6 or anti-DR antibodies. When autologous and allogeneic red blood cells were added simultaneously to lymphocytes, 78% mixed rosettes were formed, suggesting a lack of specificity in autorosette formation. A functional role for A-RFC in the autologous mixed lymphocyte reaction (A-MLR) is demonstrated by the fact that the removal of A-RFC from the responder population abrogated the proliferative response in A-MLR. Therefore, despite their non restriction, A-RFC may represent an autoreactive T cell subset. PMID- 6242347 TI - Role of distinct domains of Ia antigens in autologous and allogeneic mixed lymphocyte reactions. AB - Murine monoclonal antibodies (MoAb) to distinct determinants of human Ia antigens and low doses of prednisone induce different effects on the autologous mixed lymphocyte reaction (MLR), stimulated by PHA-T cells or by non-T cells, and on allogeneic MLRs. These results suggest that distinct domains of Ia antigens and/or mechanisms are involved in these types of MLRs. PMID- 6242348 TI - Suppressor cells and immunoregulation. AB - We have described a model system of immunoregulation in which gene products associated with both the major histocompatibility complex and the heavy-chain immunoglobulin gene complex guide a series of cellular interactions. The Igh genetic restrictions may represent the use of internal images of antigen and idiotype as suppressor-T cell receptors. The data indicate that the T-cell and B cell Igh products are distinct. The T cell-derived idiotype-like determinants are used for suppressor-T cell communications. The MHC restrictions generally involve the I-J subregion. These restrictions are imposed by the presentation of antigen or suppressor factor by specialized populations of I-J bearing accessory cells. The role of MHC products in the induction of suppressor cells has several homologies with the mechanisms responsible for the induction of H-2-restricted helper cells. First, I-region products on specialized presenting cells determine the specificity and genetic restrictions of the T cells. Thus, recognition of antigen in the context of I-A and I-E products is required for helper-T cell induction, and similarly the various suppressor-T cell subsets recognize antigen or suppressor factor presented in the context of I-J subregion-encoded antigens. Furthermore, the data suggest that the suppressor cells bear receptors for self I J products. As an additional analogy between suppressor and helper cells, we have shown that in H-2-heterozygous F1 animals at least two populations of suppressor cells can be induced, one specific for each parental H-2 haplotype. The NP and ABA suppressor-cell pathways consist of multiple cellular elements, including at least three and possibly four distinct T-cell populations and two or more distinctive accessory cell populations. These are summarized in Figure 1. The specific soluble suppressor factors produced by each suppressor-T cell subset are involved in cellular communication processes. The terminal phases of the suppressor-cell cascade are antigen dependent but involve nonspecific bystander effects. In this review we have indicated the numerous homologies between the data in the hapten systems studied in our laboratories and the various other suppressor-cell models previously described in the literature. PMID- 6242349 TI - Antigen-presenting function of the macrophage. AB - The functional significance of multiple cells--among lymphoid and nonlymphoid cells--capable of having Ia molecules on their membranes must be critically addressed. Ia is absolutely required before a cell can interact with helper T cells, but it is not clear whether the presence of this protein is all that is needed for antigen presentation. Indeed, at present, except for the macrophage, few cells have been studied for antigen presentation using a wide range of protein antigens, either soluble or particulate. On the basis of the studies discussed in the first section, it appears that the recruitment of most helper-T cell clones takes place by APC that can internalize and process the protein antigens, be they soluble or part of the structure of microorganisms. The fact that helper T cells are programmed to recognize antigen in the context of Ia, and therefore on an APC such as the macrophage, forces recognition of antigens that are altered or processed. Indeed, proteins in their native state may not remain membrane-bound for long periods; the T cells, therefore, have the opportunity to recognize the altered fragments. To this issue is added the requirement for the T cell receptor to interact with Ia molecules. The available information, therefore, leads one to conclude that APC deficient in their capacity to internalize and process proteins will not be able to present them. The finding that small peptides from a previous catabolism of proteins can be presented without further handling implies that APC with limited processing capacity could be involved in presentation of such small peptides. The different Ia-positive APC of the lymphoid organs may interact to different extents with protein antigens and collaborate with each other to bring about an effective stimulation of the clones of helper T cells. The macrophage, being the most ubiquitous cell and the one capable of interacting with many proteins, is our candidate as the major APC involved in the recruitment and enlargement of clones T cells. The observations that macrophages can release proteins partially altered implies that there may be cooperativity among the various APC. Data for this have been obtained. Most likely B cells will be found to have a limited capacity to present all antigens because of their inherent difficulties in internalizing large particulate materials. In such instances, B cells may interact with the solubilized proteins released by the macrophages. The same may apply to the Langerhans/dendritic cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 6242350 TI - Studies on the resistance to tolerance induction against human IgG in DDD mice. V. Insignificant contribution of suppressor cells to the age-related change in tolerogen susceptibility. PMID- 6242351 TI - Hepatic arterial streptozocin: a clinical pharmacologic study in patients with liver tumors. AB - Hepatic arterial infusions of streptozocin (STZ) were compared with peripheral venous infusions administered for 3 h at a dose rate of 0.5 or 1.0 g/m2 . h in five patients with liver-predominant neoplastic disease. Peripheral venous plasma STZ levels were measured during and for 3 h after completion of all infusions. Steady-state was achieved at 2 h and the elimination half-life was 35-40 min, the total body clearance was 400 ml/min, and the volume of distribution of STZ was 20 22 liters in these patients. Comparison of steady-state drug levels demonstrated minimal hepatic extraction (mean 5%). Assuming a hepatic arterial blood flow of 100-200 ml/min with a total body clearance of 400 ml/min, hepatic arterial administration of STZ can be expected to result in a three- to sixfold greater exposure of tumor in the liver compared with the intravenous route. Toxicity was minimal and two patients had evidence of response. PMID- 6242353 TI - Plain chest radiography of rheumatic heart disease. AB - This well-illustrated article considers the role of plain film examination of the adult patient with valvular heart disease caused by rheumatic heart disease. As stressed in Dr. Elliott's article in this symposium, the importance of interpreting anatomic information within the physiologic framework provided by assessing the pulmonary vasculature cannot be overemphasized. PMID- 6242352 TI - Chemotherapeutic sensitivity of acute lymphoblastic leukemia cells in culture: correlation with clinical efficacy on donor patients. AB - The establishment of permanent acute lymphocytic leukemia (ALL) lines of different phenotypes permits the study of their sensitivity to chemotherapeutic agents. The sensitivity of four ALL cell lines, two T-cell lines and one each of B- and non-T/non-B cell lines, to eight chemotherapeutic agents was studied by means of clonogenic assay. Response data were analyzed by two criteria--one based on concentrations obtainable from the elimination phase and the other based on peak concentration--both derived from pharmacokinetic studies in man. The overall correlation between the two criteria was good and only in 5 of 32 occasions were there major discrepancies. A retrospective analysis of the clinical course of the four donor patients showed that although the one set of criteria gave a positive correlation of asparaginase response in vivo, the other positively correlated the daunorubicin response, but not vice versa. No new cut-off line could be drawn to satisfy completely in vitro/in vivo correlation for all the drugs. Although the possibility exists that a leukemic cell line may not actually be predictive of chemotherapeutic responsiveness in the donor patients, our data indicate a need to reexamine the in vitro system in predictive testing of antileukemic agents. PMID- 6242354 TI - Exercise testing in lower-extremity arterial occlusive disease. AB - Exercise tolerance testing has wide application in the detection and quantitation of lower-extremity claudication. Serial follow-up after operative or nonoperative therapy permits an accurate, objective assessment of the course of the disease in each limb. Unmasking of occult aortoiliac disease, identification of pseudoclaudication, and assessment of the relative contribution of other systemic disorders in exercise limitation are further advantages of this technique. Routine exercise tolerance testing has merit for the initial and subsequent evaluations when symptoms of leg pain are produced solely by exercise. PMID- 6242355 TI - [Effect of retinoic acid and retinoid on proliferation and differentiation of human carcinoma cell line (Eca109) in vitro]. PMID- 6242356 TI - [Effects of benzo(a)pyrene metabolites from rat liver S9 fraction on sister chromatid exchange frequency of lymphocytes]. PMID- 6242357 TI - [Vitamin B12 plays an important role in biosynthesis of chuangxinmycin]. PMID- 6242358 TI - [Studies on morphology, buoyant density of virus-like particles in duck sera and disease background of duck liver]. PMID- 6242359 TI - [Comparative studies on multiplication inhibition activity of human IFN on measles and SSPE viruses]. PMID- 6242360 TI - [Neurohumoral regulation of renin-angiotensin system. I. Effects of electro stimulation of midbrain central grey and intraventricular injection of angiotensin II on release of angiotensin II from the blood-perfused cat kidney]. PMID- 6242361 TI - [Sphygmographic analysis in cerebral thrombosis]. PMID- 6242362 TI - [Clinico-pathological features of carcino-sarcoma of the esophagus (report of 4 cases)]. PMID- 6242363 TI - [Cochlear pathology in chronic intracochlear implantation in cats]. PMID- 6242364 TI - [Sensitivity prediction from the acoustic reflex (SPAR): comparison of 4 methods]. PMID- 6242365 TI - [Effect of 5-HT and anisodamine in endotoxic shock]. PMID- 6242366 TI - [Histochemical changes of ornithine carbamyl transferase in the developing rat liver]. PMID- 6242367 TI - [Preliminary observation on induction of chromosome aberrations and SCE of human peripheral lymphocytes in vitro with microwave]. PMID- 6242369 TI - [Epstein-Barr virus early antigen induction in Raji cells by Chinese medicinal herbs]. PMID- 6242370 TI - [Clinical application of peripheral angiography (report of 250 cases)]. PMID- 6242368 TI - [Organization of alpha-globin genes in Chinese with HbH diseases in Guangdong Province]. PMID- 6242372 TI - [Studies on the original plant of Swertia patens, an herbal drug of the Yi tribe]. PMID- 6242371 TI - [Polyostotic fibrous dysplasia with endocrinological changes]. PMID- 6242373 TI - [Comparison between the chemical constituents of tortoise plastron and tortoise shell]. PMID- 6242374 TI - [Comparison of the chemical constituents of Aristolochia moupinensis and Aristolochia fangchi]. PMID- 6242375 TI - [Polyacrylamide gel-disc electrophoresis of tiger bone--a new method of identifying tiger bones]. PMID- 6242376 TI - [Studies of the processing of dan-shen--the effect of various processing methods on the water-soluble phenolic constituents of dan-shen]. PMID- 6242377 TI - [Theoretical studies on the processing of mirabilite]. PMID- 6242378 TI - [Variation of the amount of chuan-xiong-qin in a decoction of Ligusticum wallichii mixed with other drugs]. PMID- 6242379 TI - [Thin-layer chromatographic determination of opium constituents in compound camphor tinctures]. PMID- 6242380 TI - [Diterpenoids of Rabdosia lasiocarpa]. PMID- 6242381 TI - [New trends in research on active alkaloid constituents occurring in Chinese medicinal herbs for cardio-cerebrovascular diseases]. PMID- 6242382 TI - [Sapogenins in the flower buds of Panax notoginseng]. PMID- 6242383 TI - [TLC densitometry of chlorogenic acid in Artemisia scoparia]. PMID- 6242384 TI - [The active constituents of Swertia patens]. PMID- 6242385 TI - [A study on the best method of compounding and preparing liu-wei-jian]. PMID- 6242386 TI - [The effect of d-catechin on the rheology of blood in patients with coronary heart disease]. PMID- 6242387 TI - [Tissue culture of qinghao]. PMID- 6242388 TI - Report of the AFCR Public Policy Committee: Current issues in pubic policy. PMID- 6242389 TI - Simplified method for purification of mouse beta 1H. AB - A simple three-step method was described for purification of murine beta 1H, one of the essential regulatory proteins of complement system. The method consists of heparin-Sepharose affinity chromatography; gel filtration on a Sepharose 6B column, and DNA-cellulose affinity chromatography. By this method over 10 mg of beta 1H can be purified by more than 200-fold from 100-ml of EDTA serum of various strains. Overall yield of beta 1H was about 45%. The purified beta 1H was homogeneous as judged by SDS-polyacrylamide gel electrophoresis and immunoelectrophoresis. The purified mouse beta 1H showed physicochemical properties very similar to those described for human beta 1H: mouse beta 1H is a beta-globulin consisting of a single polypeptide chain of molecular weight of 160,000. Purified mouse beta 1H retained its functional activity as the essential cofactor for the cleavage of fluid-phase human C3b by the human C3b inactivator. Immunization of rabbits with the purified mouse beta 1H resulted in the production of the potent and monospecific antibody. PMID- 6242390 TI - Inhibition of the complement activation by an adrenal androgen, dehydroepiandrosterone. AB - The effect of dehydroepiandrosterone (DEA), an adrenal androgen successfully used for preventing attacks in hereditary angioneurotic edema (HANE) patients was studied on the activation of classical and alternative complement pathway. The steroid inhibited both the spontaneous and immune activation of the classical complement pathway (CP), the former effect, however, was found to be more marked than the latter one. DEA exerted its inhibiting effect most probably by interfering with the internal activation of C1. Because DEA rendered HANE patients symptom free but induced only a slight increase in their serum C1-INH level, our present findings suggest that inhibition of CP activation may have a significance in the therapeutic effect of DEA and possibly of other androgens as well. PMID- 6242391 TI - Phagocytosis by human monocyte-derived macrophages. Independent function of receptors for C3b (CR1) and iC3b (CR3). AB - Human monocytes and monocyte-derived macrophages were examined for their ability to bind and ingest C3-coated sheep erythrocytes (E). Greater than 90% of monocytes and macrophages formed rosettes with EC3b and EC3bi prepared with 15,000-20,000 molecules of C3 per E. Binding of EC3b to the monocyte or macrophage surface was inhibited by rabbit anti-C3b receptor (CR1), but was not inhibited by two different monoclonal anti-C3bi receptor (CR3) antibodies. EC3bi rosette formation was inhibited by monoclonal anti-CR3, but not by anti-CR1. Monocytes and macrophages did not form rosettes with similarly prepared EC3d,g or EC3d. Macrophages cultured for 7 days, but not freshly isolated monocytes, phagocytosed both EC3b and EC3bi. This ability was a consequence of macrophage maturation, as no external stimuli were present during in vitro culture. Experiments directed to determine if EC3b was converted to EC3bi before ingestion suggested that macrophage CR1 and CR3 mediated phagocytosis independently. No evidence was obtained that during the phagocytosis assay, macrophage factor I converted EC3b to EC3bi. The number of E bound or ingested by monocytes and macrophages was dependent on the number of molecules of C3b or iC3b bound per E. Monocytes and macrophages did not require the presence of either Ca++ or Mg++ for rosette formation with EC3b, whereas both divalent cations were required for optimum rosette formation with EC3bi. The presence of divalent cations was required for macrophage phagocytosis of EC3b and EC3bi. For ingestion of EC3b, Mg++ alone was sufficient, and the addition of Ca++ did not increase the number of EC3b ingested. For ingestion of EC3bi, both Ca++ and Mg++ were required for optimal phagocytosis, and their effect was concentration dependent and additive. PMID- 6242392 TI - Demonstration by X-ray microprobe analysis of relationship between chondrocytes and tertiary surface structure of hyaline articular cartilage. AB - Blocks of hyaline cartilage from the femoral condyles of five young adult beagles dogs were quench-frozen in nitrogen slush at 63 K. The free cartilage surfaces of blocks from three animals were examined in the secondary electron mode; the remaining specimens were cut by cryoultramicrotone (approximately 188 K) tangential to the surface to expose midzone cartilage which was examined in the backscattered electron mode. A random array of gently convex prominences was apparent at the free cartilage surfaces. When X-ray emissions were recorded from tissue immediately below these elevations, the spectra proved to be similar to those derived from midzone chondrocytes. These spectra revealed high count rates for the X-rays characteristic of P and K. By contrast, in areas of free surface remote from these prominences, and in midzone intercellular matrix, larger count rates for the X-rays characteristic of Na, S. Cl and Ca were detected. The evidence supports the hypothesis that the elevations seen on the non-loaded articular cartilage of disarticulated mammalian synovial joints are the surface representations of superficial chondrocytes. PMID- 6242393 TI - The effect of vitamin A deficiency and fluoride on glycosaminoglycan metabolism in bone. AB - The effects of fluoride intake and vitamin A deficiency on glycosaminoglycan metabolism in vivo were investigated. Weanling female rats were fed either a vitamin A deficient diet ad libitum, a vitamin A supplemented diet pair-fed to the deficient animals, or the vitamin A supplemented diet ad libitum. Additionally, each vitamin A dietary group was divided into three subgroups with the animals receiving water containing 0, 10 or 50 ppm fluoride. The results showed that the groups receiving 10 and 50 ppm fluoride at all dietary levels of vitamin A had significantly higher in vivo 35SO4 incorporation in both the epiphyseal and diaphyseal regions of the bone than the animals receiving 0 ppm fluoride. The vitamin A deficient animals incorporated significantly less 35SO4 into glycosaminoglycans in the epiphyseal and diaphyseal regions of the bone compared to the pair-fed, vitamin A sufficient animals for all three fluoride receiving groups. There was no interaction between fluoride intake and dietary vitamin A levels on 35SO4 incorporation into glycosaminoglycans. Fluoride either increased sulfation or turnover of glycosaminoglycans. PMID- 6242394 TI - Elastolytic activity of peripheral blood monocytes. AB - Human peripheral blood monocytes have been purified by Ficoll-Hypaque density gradient centrifugation and adherence to plastic dishes, and assayed for elastolytic activity using insoluble [3H]elastin. Approximately 5-10 micrograms of elastin are solubilized at pH 7.5 per mg protein per h. The specific activity in monocytes varies between 3 and 15% of that of neutrophils obtained at the same time from the same subjects. The enzymatic activity derives principally from monocytes. Lymphocytes purified by Sephadex G-10 gel filtration chromatography exhibit only trace elastolytic activity, while neutrophils comprise 1% or less of the cell population. Monocyte elastolytic activity is inhibited by alpha-1 antitrypsin and Succinyl-Ala-Ala-Pro-Val-chloromethylketone indicating that it is a serine-type protease. When extracts of monocytes are analyzed by gel filtration, the elastolytic activity appears in large molecular weight forms; however, these forms are not observed when extracts of monocyte lysosomes are analyzed. Such variation in forms is also seen with neutrophil extracts. Monocytes are a source of elastolytic activity for various physiologic and pathologic actions in the lung and other organs. PMID- 6242395 TI - Stabilization of pericardial tissue by glutaraldehyde. AB - The effect of glutaraldehyde on pericardial tissue has been studied with special reference to the degree of chemical modification, thermal stability and enhancement of the resistance to proteolytic digestion. The nature of the cross links depends on time and reagent concentration. At least two populations of lysine and hydroxylysine residues can be distinguished on the basis of their reactivity against the aldehyde. The appearance of these families is not dependent on the structural integrity of the tissue. The time course of the tissue modification is not modified by removing lipids and proteoglycans from the biomaterial. Highest thermal stability is obtained by long-term modification at low reagent concentration. PMID- 6242396 TI - Extracellular matrix (ECM) proteoglycans produced by cultured bovine corneal endothelial cells. AB - The nature of the proteoglycan(s) (PG) found in the extracellular matrix (ECM) layer produced by cultured bovine corneal endothelial (BCE) cells is analyzed. The PG(s) account for approximately 5 to 6% of the dry weight of the ECM, regardless of the amount of extracellular soluble PG available in the medium. A 4 M guanidinium chloride (GuCl) extract of ECM was separated on a dissociative cesium chloride (CsCl) gradient (1.25 g/cm3 starting density). Results showed one main peak of PG substance(s) comprising 91% of the total labelled substance and uronic acid, banding at a specific buoyant density of 1.29 g/cm3. The molecular weight of this major PG(s) as estimated by gel filtration on Sepharose CL-4B ranged from 0.5 to 0.7 X 10(6). Further chemical analysis of the main PG(s) band revealed a protein moiety accounting for 45% of the weight and carbohydrates glycosaminoglycans (GAG) accounting for the remaining 55%. Analysis of the GAG chains (over the entire gradient) showed a composition, based on the susceptibility of the PG substance(s) to degrading enzymes, of 50% heparan sulfate, 43.5% dermatan sulfate, and 6.5% chondroitin 4- and 6-sulfate chains. BCE cell cultures grown in the presence of beta-D-xyloside produced an ECM lacking more than 90% of the GAG content found in the control ECM. The medium soluble GAG chains, produced in vast excess in cultures grown in the presence of beta-D-xyloside, are composed mainly of chondroitin 4- and 6-sulfates. PMID- 6242397 TI - Collagen fibril diameters and glycosaminoglycan content of skins--indices of tissue maturity and function. AB - Samples of anatomically and functionally distinct regions of the skin of a variety of altricial and precocial animals were taken at various stages of development from birth to beyond maturity. The glycosaminoglycan (GAG) content and composition of the tissues were determined by chemical analysis and the collagen fibril diameters measured by transmission electron microscopy. The fibril diameters of the skins of two fish and a bird were also assessed for comparison. Analysis and comparison of the data collected show that there was a significant correlation between collagen fibril diameter distribution, GAG type and amount, and functional load-bearing of the various skins, and that the variations in the biochemical and physical composition of the tissues at different stages of development could be related to both their post-conceptual maturity and their prospective functional loading. PMID- 6242398 TI - The urinary excretion of heparan sulfate by juvenile- and adult-onset diabetic patients. AB - The daily urinary excretions of total polymeric glycosaminoglycans and of polymeric heparan sulfate have been measured in the urine of juvenile-onset and adult-onset diabetics of both sexes and in those of normal controls. The results indicate that diabetic patients excrete more polymeric heparan sulfate than their controls, either in an absolute amount or as a percentage of the total glycosaminoglycans excreted. These results suggest that in the course of diabetes there is an increased degradation of heparan sulfate to large oligosaccharide fragments. These are excreted before being completely degraded to monosaccharides and inorganic sulfate. PMID- 6242399 TI - Synthesis and sulfation of glycosaminoglycans in fibroblasts from a patient with Lowe's syndrome. AB - Glycosaminoglycans of cultured normal skin fibroblasts and fibroblasts of a patient with Lowe's syndrome were labelled for 72 h with either [14C]-glucosamine or with 35SO4. For each culture, the incorporation was measured in total glycosaminoglycans per culture and in the glycosaminoglycans isolated from the intracellular, pericellular and extracellular pools. The synthesis of the sulfated glycosaminoglycans in the three pools and the total 35SO4 incorporation in the glycosaminoglycans of the two types of cultures were strictly comparable. However, Lowe's intracellular glycosaminoglycans were less sulfated than the corresponding normal ones. Undersulfated glycosaminoglycans were present in the pericellular pool of Lowe's cells, while hypersulfated ones were present in their extracellular pool. Degradation of the different pools with chondroitinases indicated that hyposulfated chondroitin 4- and 6-sulfates are present on the cell surface of Lowe's cells, where an increased amount of normally sulfated heparan sulfate may be demonstrated. This abnormal distribution of pericellular glycosaminoglycans in Lowe's cells has been described already. However, the demonstration that the total incorporation of 35SO4 is normal in Lowe's cells does not support the possibility that this abnormal distribution is the consequence of excessive hydrolysis of the phosphosulfate bond of adenosine 3' phosphate 5'-phosphosulfate. PMID- 6242400 TI - Comparison of the thermal stabilities and solubilities of human hypertrophic scar, normal scar and normal skin collagens. AB - The thermal stability and solubility profiles of human hypertrophic scar collagen have been measured and compared with those of the collagens present in human normal scar, human normal skin and a lathyritic dermal tissue. The thermal stability profiles of the hypertrophic scar collagens were found to be very similar to each other and to closely resemble that of lathyritic collagen but differ significantly from those obtained with the other dermal collagens. The hydrothermal solubility profiles did not, however, show a clear distinction between normal and hypertrophic scars. PMID- 6242401 TI - Huntington disease: estimation of heterozygote status using linked genetic markers. AB - The recent finding of a closely linked DNA marker to the Huntington Disease gene allows the opportunity for prenatal and preclinical diagnosis. The methodology for using these markers for prediction in late age of onset disorders is discussed. Since these methods are both difficult and complex for the majority of genetic counselors, a simple solution is suggested. This involves using the well known linkage program LIPED and running it twice for a given consultand, once assuming he carries the gene and once that he is homozygous normal. This will allow accurate predictions for counselors with limited backgrounds in pedigree analysis. PMID- 6242402 TI - [Detecting handicaps]. PMID- 6242403 TI - Vaccination against hepatitis B virus infection in neonates. AB - The efficacy of hepatitis B virus vaccine to prevent the vertical transmission of hepatitis B virus (HBV) in infants born to HBsAg carrier mothers was assessed in 20 mother-infant pairs. A dose of 10 micrograms of HBV vaccine was injected intramuscularly at 0, 30 and 180 days after birth to newborn infants. Neither local nor systemic reaction was observed after the administration of HBV vaccine. The incidence of persistent HBsAg carrier infants born from e-antigen positive HBsAg carrier mothers in HBV vaccine treated group was only 37.5% at one year of age as compared to 85.7% in the untreated control group. Anti-HBs developed in 88.2% of infants after the third dose of HBV vaccination with a mean anti-HBs titer of 1733.1 IU/l. It is concluded that HBV vaccine was effective and safe in reducing the rate of vertical transmission of HBV from the HBsAg carrier mothers to their infants. The vaccine was also immunogenic since almost 90% of the immunized infants were able to produce anti-HBs antibody in high titer after the third dose of vaccination. PMID- 6242405 TI - Typing coagulase-positive staphylococci of different origin with Blouse and Meekins' phages. AB - Making use of four experimental Blouse and Meekins' (I) phages 06, 40, 58, and 93, derived from Staphylococcus intermedius strains of canine origin, 631 strains of three coagulase-positive staphylococcal species were typed. The typability was in a great extent dependent on the origin of the tested strains. Of 310 S. aureus strains 23 (7%) at RTD and 45 (15%) at 100 X RTD were typable, all without exception of C biotype from cows and sheep. Of 281 S. intermedius strains 208 (74%) at RTD and 14 (5%) at 100 X RTD were lyzed with the above-mentioned I phages. The typability of the isolates in the nine groups from buzzards, pigeons, rooks, dogs, wild ducks, pheasants, foxes, horses, and mink ranged from 59 to 90%. No special relationship was recorded between the origin of the strains and the phage patterns. When testing 135 S. hyicus subsp. hyicus strains nearly one fifth (19%) of them were typable, for the most part at RTD. On the contrary, all 36 S. hyicus subsp. chromogenes strains were resistant to the used phages. The usefulness of the I phages for classificatory aims was discussed. PMID- 6242404 TI - Electroencephalography in diffuse encephalopathies. PMID- 6242406 TI - Semantic memory content in permastore: fifty years of memory for Spanish learned in school. AB - Retention of Spanish learned in school was tested over a 50-year period for 733 individuals. Tests of reading comprehension, recall, and recognition vocabulary and grammar were administered together with a questionnaire to determine the level of original training, the grades received, and rehearsals during the retention interval in the form of reading, writing, speaking, or listening to Spanish. Multiple regression analysis shows that retention throughout the 50-year period is predictable on the basis of the level of original training. The great majority of subjects rehearse so little that the data reveal no significant rehearsal effects. The analysis yields memory curves which decline exponentially for the first 3-6 years of the retention interval. After that retention remains unchanged for periods of up to 30 years before showing a final decline. Large portions of the originally acquired information remain accessible for over 50 years in spite of the fact the information is not used or rehearsed. This portion of the information in a "permastore" state is a function of the level of original training, the grades received in Spanish courses, and the method of testing (recall vs. recognition), but it appears to be unaffected by ordinary conditions of interference. The life-span frequency distribution of learned responses is discontinuous; one portion of the response distribution has life spans of 0-6 years, the other portion, life spans in excess of 25 years, and no responses have life spans of 6-25 years. This suggests a discrete transition into a permastore state during the extended period of original training. Analysis of successive relearning processes over extended time periods is deemed essential for an understanding of the acquisition of permanent semantic memory content. PMID- 6242407 TI - On the pretense theory of irony. AB - We propose a pretense theory of irony based on suggestions by Grice and Fowler. In being ironic, the theory goes, a speaker is pretending to be an injudicious person speaking to an uninitiated audience; the speaker intends the addresses of the irony to discover the pretense and thereby see his or her attitude toward the speaker, the audience, and the utterance. The pretense theory, we argue, is superior to the mention theory of irony proposed by Sperber and Wilson. PMID- 6242408 TI - How normal and retarded individuals monitor and regulate speed and accuracy of responding in serial choice tasks. AB - These experiments investigate whether or not differences in the way that retarded and nonretarded individuals monitor and regulate speed and accuracy of responding contribute to the slower and more variable performance of retarded subjects on choice reaction time (RT) tasks. Rabbitt (1979, 1981) suggested that efficient choice RT performance is mediated by subjects tracking increasingly faster RT bands on successive trials until, by making and recognizing errors, they discover those very fast RT levels that should be avoided and those safe bands, just above typical error levels, that should be tracked. Experiments 1A and 1B established that most retarded subjects detect their errors as efficiently as nonretarded controls, a finding that excludes the possibility that retarded subjects do not monitor accuracy efficiently but achieve comparable levels of accuracy by consistently responding within very slow RT bands that minimize likelihood of errors. Experiment 2 showed that while a qualitatively similar trial-by-trial tracking mechanism mediates the performance of both groups, retarded subjects are less efficient at constraining RTs within very fast, but safe, bands. Increasing error probabilities at longer RTs suggest that momentary fluctuations in stimulus discriminability and/or attention are factors affecting RT variability in retarded subjects. The RT patterns for various sequences of correct responses initiated and terminated by errors suggest that the effective past experience (EPEX) guiding trial-by-trial RT adjustments of retarded subjects is short and inadequate, and it was argued that this can account for much of the remaining RT variability contributing to retarded-nonretarded differences. Not only does a short EPEX increase variability by giving rise to long error-free sequences of slower than average RT but also, when combined with occasional specified random fluctuations, it suggests why retarded subjects can achieve, but not sustain, RT levels maintained by nonretarded subjects. PMID- 6242409 TI - Holistic and analytic modes of processing: the multiple determinants of perceptual analysis. AB - With the use of the criterion of privileged axes, a set of experimental studies establishes that analytic processing of saturation and brightness, prototypical integral dimensions, does sometimes occur. Still, it is less frequent and less successful than analytic processing of separable dimensions. The studies identify several factors that influence whether or not analytic processing occurs. Among them are the following: (a) stimulus factors, in addition to the choice of dimensions (e.g., the magnitude of dimensional differences); (b) task factors (e.g., the degree to which analytic processing is encouraged by instructions or by implicit task demands, the amount of time available for processing); and (c) subject factors (e.g., the amount of experience that the perceiver has had with the stimuli in tasks that encourage stimulus analysis). PMID- 6242410 TI - Measuring efficiency of selection from briefly exposed visual displays: a model for partial report. AB - In the proposed model for partial report, performance reflects the number of targets in a short-term memory buffer. The total number of items (targets, distractors, or extraneous noise) entering the buffer is independent of the number of targets and distractors in the stimulus. Entrance is determined by selective sampling according to a Luce (1959) ratio rule. The model was tested in a variety of conditions with partial reports based on brightness, color, shape, or alphanumeric class. With three parameters, the model accounted for 99% of the variance with number of targets and number of distractors in data obtained by averaging across conditions. Parameter K (number of items entering the buffer) showed little variation with the selection criterion, and estimates for parameter epsilon (total impact of extraneous noise with impact per target as the unit) were rather small. Estimates for parameter alpha (impact per distractor with impact per target as the unit) varied widely across conditions. Parameter alpha is a measure for the efficiency of selecting targets rather than distractors. PMID- 6242411 TI - Are lexical decisions a good measure of lexical access? The role of word frequency in the neglected decision stage. AB - Three experiments investigated the impact of five lexical variables (instance dominance, category dominance, word frequency, word length in letters, and word length in syllables) on performance in three different tasks involving word recognition: category verification, lexical decision, and pronunciation. Although the same set of words was used in each task, the relationship of the lexical variables to reaction time varied significantly with the task within which the words were embedded. In particular, the effect of word frequency was minimal in the category verification task, whereas it was significantly larger in the pronunciation task and significantly larger yet in the lexical decision task. It is argued that decision processes having little to do with lexical access accentuate the word-frequency effect in the lexical decision task and that results from this task have questionable value in testing the assumption that word frequency orders the lexicon, thereby affecting time to access the mental lexicon. A simple two-stage model is outlined to account for the role of word frequency and other variables in lexical decision. The model is applied to the results of the reported experiments and some of the most important findings in other studies of lexical decision and pronunciation. PMID- 6242412 TI - Processing stages in overlapping tasks: evidence for a central bottleneck. AB - This article examines the attentional limits responsible for task slowing in the overlapping task (refractory period) paradigm. Five experiments are reported in which stimulus factors were manipulated in visual search tasks performed in isolation or temporally overlapping with another task. Bottleneck models suggest that second-task slowing is caused by postponement of "attention-demanding" stages of the second task, while earlier "automatic" stages proceed unhindered. A prediction was derived from this class of models, namely that in the overlapping task condition the effect of second task factors that slow automatic stages should be reduced, whereas the effect of factors slowing later nonautomatic stages should be unchanged. The data (Experiments 1-4) exhibit such a pattern and suggest that encoding and comparison stages of the second task, but not response selection, occur in parallel with work on the first task. The absence of overadditive interactions in these experiments, and also the effects of manipulating first-task factors in Experiment 5, seems to argue against capacity sharing as the source of the slowing in this task combination. Some implications of these results for attention theory are discussed. PMID- 6242413 TI - Motion direction identification in random cinematograms: a general model. AB - The cinematograms of 12 two-state elements arranged in the clock positions in space and in a sequence of adjacent 100-ms frames in time were used as stimuli. Some positions in each frame (or all 12 of them) could be labeled as "domain" ones, and every element that was T frames and S positions (clockwise or counterclockwise) apart from a domain element could repeat the latter's state with probability P. The probability of the rotation direction identification was obtained as a function of T, S, P, number of frames, and the domain positions selection scheme. A generalized version of the reversed phi phenomenon was obtained: if P less than .5, then the psychometric value lies below .5 level. All the data can be accounted for by a simple model according to which the choice of direction is based on the counts of the different types of dipoles, each type being characterized by the probability and the weight of its count: In most situations all dipoles but the shortest ones (connecting the neighboring elements of successive frames) can be ignored. PMID- 6242414 TI - Dependence, independence, and emergence of word features. AB - The degree to which a letter is perceived to be an e rather than a c is a function of the central, horizontal bar, which can be made to be more or less present in any given stimulus. By this means, word-form stimuli were produced through the independent, continuous manipulation of e versus c and of r versus h in two word frames (wat-- and --ase) yielding stimuli that ranged between water and watch in the former instance and between erase and chase in the latter. The identification probabilities for these stimuli were well accounted for in each case by a version of a fuzzy propositional model that is based on the assumption of independent features, indicating that the manipulated features within each word frame were not perceptually interdependent. However, the probabilities differed systematically between the two stimulus matrices; this means that there must be some other kind of higher order effect involved in identification. The hypothesis that the interaction was due to an emergent word envelope feature was rejected on the basis of the model analysis. PMID- 6242415 TI - Selective adaptation of monocular and binocular neurons in human vision. AB - Psychophysical techniques were used to examine how subpopulations of visual neurons varying in their ocular dominance interacted in determining performance on a visual task. Using an asymmetric alternating adaptation of the left and right eyes, we manipulated the sensitivity of monocularly driven neurons while keeping the sensitivity of binocularly driven neurons constant. Relative threshold elevations were measured in the left eye, right eye, and both eyes of five observers following different ratios of alternating adaptation. It was found that whereas monocularly measured aftereffects varied monotonically as a function of the adaptation duration of the measured eye, the magnitude of the binocularly measured aftereffect remained constant regardless of how the adaptation was divided between the two eyes. This suggests that neurons differing in their ocular dominance pool their activity in determining sensitivity to a test target. PMID- 6242416 TI - Word shape's in poor shape for the race to the lexicon. AB - Current models of fluent reading often assume that fast and automatic word recognition involves the use of a supraletter feature corresponding to the envelope or shape of the word when it is printed in lowercase. The advantages of mixed case over pure case and of pure lowercase over pure uppercase have often been taken as evidence favoring the word-shape hypothesis. Alternative explanations for these phenomena are offered. Experiment 1 shows that previous demonstrations of word-shape effects during proofreading are better described as individual letter effects. Experiments 2-4 explore the possibility that word shape facilitates lexical access through uncertainty reduction. In all three experiments performance on words with rare shapes is compared to those with common shapes. There were no effects of shape frequency in either tachistoscopic recognition or lexical-decision tasks. This was true regardless of the degree to which the visual shape cue was supplemented by the nonvisual factors of familiarity and expectancy. Possible reasons why fluent readers ignore word shape are discussed within the framework of a model that assumes that automatic word recognition is mediated by the activation of abstract letter identities. PMID- 6242418 TI - Visually perceiving distance: a comment on Shebilske, Karmiohl, and Proffitt (1983). AB - Shebilske, Karmiohl, and Proffitt (1983) interpret their data as showing that (a) the reference tonus level of the extraocular muscles controlling vergence is affected by everyday conditions of close viewing, and (b) this naturally induced phoria affects the visual perception of distance under natural viewing conditions. We note that these interpretations do not fully concur with the data presented--for example, the second conclusion favorably conflates partial results from two separate experiments--and we identify a number of confoundings that reduce the likelihood that the reported inaccuracies in distance judgments were due to variations in efference. PMID- 6242417 TI - Evidence against late selection: stimulus quality effects in previewed displays. AB - Strong late-selection theories of visual attention assert that when multiple stimuli belonging to familiar categories are presented, their identities are computed automatically and tagged for their locations. When selection by location is required, the identities are said to be retrieved without any need to repeat the perceptual processing. Five experiments designed to test this account are reported. All included a condition in which a display of eight characters was previewed for several hundred ms; a bar probe then designated one character the target for speeded classification. Stimulus factors that slow the character encoding process were manipulated. If selection is late, then such factors should have no effect in this condition because the probe occurs after automatic encoding is complete. There was no evidence of any such reduction in these factors' effects on reaction times or errors. The results were unchanged when catch trials with postdisplay masks were included, to discourage any optional delay of encoding. Several possible accounts are considered of how the strong late-selection model may be wrong, even if parallel encoding occurs in various situations. PMID- 6242419 TI - Efferent factors in natural event perception can be rationalized and verified: a reply to Turvey and Solomon. AB - Contrary to the view that ambient light information unequivocally specifies phenomenal events, recent research suggests that natural event perception is determined by processes that pick up and combine visual and motor information. This thesis is challenged by Turvey and Solomon (1984). The present article responds to their misgivings by elaborating empirical methods and theoretical arguments of past work. A control experiment is also presented on pointing measurements of distance illusions related to esophoric shifts of eye convergence that are induced by near work. The soundness of both the empirical methodology and the theoretical arguments in support of the original thesis is upheld. PMID- 6242420 TI - Chemosensitivity tests by a miniclone technique. AB - A modified miniclone method has been adopted to tissue culture testing of sensitivity to cytostatic drugs. The technique permits detailed microscopic clonal analysis of multiplication of single cells under conditions of 100% plating efficiency of certain selected established tumor lines or normal cells. Three different response parameters were distinguished--cytolysis, cytostasis and replicative capacity of cell fraction capable of multiplication. Notable differences were found among the five drugs tested--adriamycin, alkeran, BCNU, platinol and streptozocin. PMID- 6242421 TI - Diagnostic specificity of the monoclonal anti-CALLA antibody VIL-A1 in leukemia and malignant lymphoma. AB - VIL-A1 is an anti-CALLA antibody which binds efficiently and exclusively to CALLA positive cells. When the cell type specificity of VIL-A1 is studied in acute leukemias and lymphomas, results show that in those leukemias which could be characterized by cytochemical and morphological methods, VIL-A1 reactivity was specific for cells of lymphoid origin. It can therefore be assumed that VIL-A1 positive AUL cells (in this case 4 out of 9 patients) are also lymphoid in origin. In no case were AML blasts found to be positive with this antibody. Seventy-four per cent of the 88 ALL patients were positive (L1 + L2) whereas none in the L3 subgroup were positive, and 48% of CML patients in blastic crisis were positive. Of the low grade non-Hodgkin malignancies, only CB/CC was positive, distinguishing it from the CC type which was negative. Of the high grade lymphomas IB was found to be negative, while the others showed a heterogeneous picture which was not related to other immunological parameters. PMID- 6242422 TI - A comparative study on glucagon effect between McArdle disease and Tarui disease. AB - Pretreatment with glucagon relieved patients with McArdle disease from muscular symptoms during exercise and enhanced exercise performance, though it did not produce any improvement in patients with Tarui disease. The difference in glucagon effect between the two diseases was clearly demonstrated in the bicycle ergometer exercise tests. In addition, the semi-ischemic forearm exercise tests performed after glucagon injection showed that increased lactate production was significantly induced by exercise in McArdle disease, but it was not the case in Tarui disease. In McArdle disease, the augmentation in exercise-induced lactate production was also observed after administration of glucose, or glucose plus insulin, but it was neither observed after administration of insulin alone nor after arginine or epinephrine administration. These findings suggest that the beneficial effect of glucagon in McArdle disease is due to the enhanced utilization of circulating glucose through the muscular glycolytic pathway realized in the coexistence of hyperglycemia and hyperinsulinemia. PMID- 6242423 TI - [The significance of medical history in the dental management of children]. PMID- 6242424 TI - [Patients with glucose 6-phosphate dehydrogenase (G-6-PD) deficiency and their dental treatment]. PMID- 6242425 TI - [Phenylketonuria in children: problems of special interest to the dentist]. PMID- 6242426 TI - [The inheritance of caries/Cooley's disease]. PMID- 6242427 TI - [Histopathological study of changes in tissues adjacent to the dental pulp during restoration with composite materials using traditional technics and using controlled polymerization with infrared 904 nm. laser light]. PMID- 6242428 TI - [Evaluation of water absorption by a composite, Adaptic, polymerized with 904 nm. laser light, in relation to normal polymerization]. PMID- 6242429 TI - [Evaluation of the hardness of a composite, Adaptic, polymerized with 904 nm. laser light, in relation to normal polymerization]. PMID- 6242430 TI - [Evaluation of the wear of a composite, Adaptic, polymerized with 904 nm. laser light, in relation to normal polymerization]. PMID- 6242432 TI - [The role of orthopantomography in dentistry in thalassemia (I)]. PMID- 6242431 TI - [Experimental studies and comparison using optical microscopy of the adhesion of a composite that is autopolymerized and controlled polymerized using 904 nm. laser light (Adaptic)]. PMID- 6242433 TI - [Oral characteristics of Mediterranean anemia and adequate prevention (II)]. PMID- 6242434 TI - [Epidemiological ideas for the organization of tertiary prevention]. PMID- 6242435 TI - [The absence of the internal arms of dynein as a cause of the immotile cilia syndrome]. AB - Two children aged 9 and 8 years respectively presenting upper and lower respiratory tract infections from early childhood are presented. In both, nasal mucociliary transport was impaired (greater than 30 min) and electron microscopic examination showed cilia devoided of the inner dynein arms. This ciliary defect is one of those recognized as a cause of the Immotile Cilia Syndrome but is very rare, having been described only once in a boy affected with Kartagener's syndrome, which in turn has been reclassified in the Immotile Cilia Syndrome. Therefore the absence of inner dynein arms observed by us in the respiratory cilia of these two children clearly indicated that similarly to many other genetic disorders the immotile cilia syndrome may be determined by many defects in the axonemal structure. PMID- 6242436 TI - [Proposal for hepatologic functional diagnosis in children]. PMID- 6242437 TI - The neuropsychology of facial expression: a review of the neurological and psychological mechanisms for producing facial expressions. PMID- 6242438 TI - [The reporting of exotic diseases in the Pedro Kouri Institute of Tropical Medicine in 1982]. PMID- 6242439 TI - Lay concepts and strategies for handling symptoms of disease. A sample of adult men and women experiencing back pain symptoms. AB - A population sample of 60 men and women who had experienced back pains were interviewed in-depth with semi-structured techniques. Though two thirds of the sample had symptoms of severe or moderately severe character, less than half had any current contact with doctors. Interviews were taped and analysed qualitatively. Results show that almost all respondents continually develop ideas and concepts about their disease built upon the experiences and experiments of everyday activities over a long period, rather than upon medical information. Most respondents subscribed to a multifactorial view of the disease and some had quite sophisticated models of processes leading to symptom emergence. However, models almost invariably were of the "black-box type", specifying influences and outcomes but being blank on what was going on inside the body. Most respondents preferred not to see themselves as ill. They were nevertheless concerned with disease concepts and causes because correct disease modelling would give them information on the likely future development of symptoms, i.e. prognostic information, which in turn reduced anxiety and strengthened their mental and practical control of illness. Control of illness was practiced in several ways. We identified four main types of strategy towards illness: Ignoring/neclecting symptoms of disease. Routine treatment during symptom periods (professional/self care). Preventive behaviour. Permanent change or modification of life situation. Roughly half of respondents were strategy-two users. The current concept and policy of individual health responsibility is discussed in light of the results. PMID- 6242440 TI - Selected papers presented at the XIIth Symposium of the European Society of Osteoarthrology on the Biology of the Cartilage. Debrecen, Hungary, August 15-17, 1983. PMID- 6242441 TI - Professor Istvan Krompecher 1905-1983. PMID- 6242442 TI - Regulatory aspects of glycosaminoglycan biosynthesis. AB - The control of glycosaminoglycan biosynthesis was investigated by studying the kinetic and regulatory properties of some enzymes involved in the formation of UDP-sugar precursors: UDP-N-acetylglucosamine 4'-epimerase, catalyzing the interconversion of hexosamine precursors and UDP-glucose dehydrogenase and UDP glucose 4'-epimerase, utilizing UDP-glucose for the formation of uronic acid and galactose precursors. The study was carried out in tissues with different glycosaminoglycan production: bovine cornea, producing both chondroitin sulfate and keratan sulfate, and newborn-pig epiphysial-plate cartilage, producing mostly chondroitin sulfate. The biosynthesis of hexosamine precursors appeared to be regulated by the value of the NAD/NADH ratio. This control mechanism regulated also the activities of both UDP-glucose dehydrogenase and UDP-glucose 4' epimerase and, therefore, it could correlate the biosynthesis of glycosaminoglycan precursors with the redox activity of the cell. At the level of UDP-glucose utilization two other control mechanisms were demonstrated: the different affinities of UDP-glucose dehydrogenase and UDP-glucose 4'-epimerase for UDP-glucose in tissues with different glycosaminoglycan production and the cellular concentration of UDP-xylose. This sugar-nucleotide inhibited UDP-glucose dehydrogenase, but did not affect the UDP-glucose 4'-epimerase activity; therefore, and increase of its cellular concentration may result in a decreased chondroitin sulfate synthesis and in an increased keratan sulfate formation. PMID- 6242443 TI - Application of new techniques to separation of proteoglycan aggregates from normal and destabilized rabbit articular cartilages. AB - Proteoglycans were prepared from rabbit articular cartilages by classical techniques employing 4.0 M guanidine. HCl by transport ultracentrifugation techniques on the purified proteoglycans, present. A new method of extracting the cartilage with 0.4 M guanidine. HCl in the presence of highly purified collagenase is presented. The same yield of proteoglycans on extraction of normal cartilage was obtained as with the classical technique, but a larger proportion of intermediate and large aggregates was obtained with the new than with the classical methodologies. The osteoarthritic cartilage was obtained from 6 month old animals, 3 months after a partial medial meniscectomy had been performed. The profile of proteoglycans from osteoarthritic cartilage consisted predominately of monomers, and a small content of aggregates spread over intermediate and large size ranges. It is postulated that by the methods of extraction, the profile of proteoglycan aggregates present in vivo is more faithfully reproduced than obtained by the classical methodologies. PMID- 6242444 TI - The association of a newly discovered protein, called chondrocalcin, with cartilage calcification. AB - A newly identified calcium binding protein called chondrocalcin with two subunits of molecular weight approximately 35 000 has been studied in bovine, rat and human cartilage matrix using a monospecific polyclonal antibody. Although it is present in small amounts in non-calcifying cartilage, it occurs in local high concentrations wherever cartilage calcification is observed, namely in the calcifying part of the growth plate and in calcified articular cartilage. Immunoelectron microscopy revealed that it is present in exactly the same discrete sites where mineral is first detected. Thus it may act as a nucleating agent for apatite formation. It is deposited in the same sites where unusual local high concentrations of proteoglycan and link protein are detected by immunoelectron microscopy. Chondrocalcin may bind either directly or indirectly to these molecules. Its occurrence within hypertrophic chondrocytes immediately prior to its extracellular appearance suggests that it is synthesised and released by these cells. Its absence from osteoid during intramembranous calcification indicates a selective involvement in endochondral calcification. PMID- 6242445 TI - Current concepts about the collagen components of cartilage tissue. PMID- 6242446 TI - The importance of minor collagenous chains in the articular cartilage. AB - This is a review of the present knowledge on the newly-described minor cartilage collagens. The authors deal with the nomenclature, methodology, structure and function of the minor collagens based on both literary data and their own results. The authors were the first to describe the occurrence of minor collagens in adult human articular cartilage and the change of the minor collagen content with age and osteoarthrosis [25]. The methods used by different groups for fractionation of minor collagens are different. As the recommended pepsin digestion used for solubilization of these collagens gives different results for the size of one of the minor collagens called M-collagen, special attention should devoted to the method used. The differential salt fractionation of pepsin solubilized collagen was found the best. In this case the molecular structure of the M-collagen remained intact. In the neutral salt extraction technique recommended recently by Burgeson et al. [5], yield of collagen from sample is high, M-collagen is degraded. The greatest solubilization of collagen was achieved by the cyanogen bromide technique. The mixture of peptides from different proteins, however, requires further fractionation. The authors propose to investigate minor collagens in tissue samples obtained from biopsies and in synovial fluid. PMID- 6242447 TI - Changes in collagen metabolism--another look at osteoarthrosis. AB - Collagen types I and III were isolated from osteoarthrotic cartilage. Immunofluorescence study has shown that these two collagen types are present in the deep layers of cartilage. Additional staining for fibronectin revealed the presence of the cell-adhesive protein in osteoarthrotic cartilage. Neither collagen type I and type III nor fibronectin were found in control cartilage. A passive haemagglutination assay determined anticollagen antibodies (against types I, II and III) in sera of some osteoarthrotic patients. PMID- 6242448 TI - Regulation of DNA synthesis in articular cartilage. PMID- 6242449 TI - The significance of cell contacts for the differentiation of the skeletal blastema. AB - Isolated limb bud cells from day-11 and day-12 mouse embryos served to investigate the significance of adhesion and contact formation for triggering cartilage differentiation in the blastema. In monolayer culture at low cell density, fibroblastlike cells developed which produced collagen type I and pro III as well as fibronectin. In mass culture at high cell density, however, cartilage tissue formed whose matrix contained collagen type II and cartilage specific proteoglycans. Other experiments showed that the existence of an overgrowth phenomenon and a cartilage-inducing factor is not the reason for differentiation differences. An increased adhesion tendency and the occurrence of gap junctions speak for changes in the cell membrane during blastema formation. These notions are supported by investigations using fluorochrome-labelled lectins which show that sugar chains with terminal galactosyls only exist during the blastemal stage. It is assumed that adhesion gives the signal for chondrogenesis. The differentiation signal is then stabilized and passed on through cellular communication via gap junctions. After the onset of chondrogenesis, the cell membrane changes again and the gap junction-containing segments are incorporated and disaggregated. PMID- 6242451 TI - Mechanisms of cartilage precursor replacement by bone in the mammalian skeleton. AB - The initiation of the endochondral process in ontogenesis is preceded by structural and metabolic preparation of the cells of cartilage anlages of the skeleton as well as the satellite cells of the vascular terminations adjoining the cartilage. In the cartilage anlage, due to a progressive specific biosynthesis, the macromolecular chondroitin-protein complexes capable of binding a large amount of water, are accumulated. As a result the volume of a swelling chondrocyte increases twentyfold or more and a high hydrostatic tension is created within it. At the same time the metabolic situation within the cartilage favours a local concentration, near the hypertrophic chondrocytes, of the perivascular cells possessing an increased resorptive function. The resorption of the cartilage partition walls by these cells leads to the opening of swollen chondrocytes. The blood cells and the cells of the blood capillaries themselves are engulfed through the resulting crater into the emptied lacuna. In the lacuna the conditions of stasis are created which promote local redistribution of the supplied cells and reutilization of the cartilage destruction products. The perivascular cells concentrated along the remnants of the cartilaginous matrix are gradually differentiated into preosteoblasts and osteoblasts. The endosteal bony laminae are built on the remnants of the cartilaginous matrix. The perivascular cells of the apical zone of a lacuna retain their clastic function and continue spreading of the endochondral process on the adjacent chondrocytes. In the course of the successive destruction of hypertrophic chondrocytes, the system of vessels is formed in the endochondral centre, according to the sinusoid pattern. PMID- 6242450 TI - Induction of heterotopic and orthotopic cartilage and bone formation in mice. AB - Heterotopic cartilage, bone and bone-marrow formation was achieved in mice by transplantation of a variety of xenogeneic established cell lines, by the transitional epithelium or by implants of demineralized bone matrix. The pattern and the sequence of events were always the same, regardless of the inducer used; viz., hyaline cartilage appeared 6-7 days after implantation, and endochondral bone formation followed. However, in cases of allogeneic implants of transitional epithelium into species other than the mouse, an intramembranous osteogenesis was the main mode of bone formation. When the yield of induced bone was high enough, a true myelopoiesis developed after three weeks. Heterotopically-induced bones had a relatively short life-span. Periosteal membranes of bones at the sites of sarcomes induced by M-MSV responded with rapid and extensive proliferation, with subsequent bone and, sometimes, hyaline cartilage deposition. This phenomenon was observed in long and cranial bones. However, bone induced heterotopically by demineralized bone matrix did not respond in such a way to the presence of M-MSV induced sarcoma, suggesting that the connective tissue-encapsulated heterotopic bone was not a functioning periosteum. M-MSV-induced sarcoma also stimulates proliferation of elastic cartilage. PMID- 6242452 TI - Contributions of light and electron histochemical techniques to the study of proteoglycan function in cartilage. PMID- 6242453 TI - Heterogeneity of proteoglycan particles in thin sections and replicas of human articular cartilage. AB - Proteoglycans were studied in articular cartilage of human femoral condyles. On the basis of the histochemical data obtained by means of light microscopy (AB + CEC MgCl2; pre-incubation with hyaluronidase or with chondroitinase ABC), the proteoglycan concentration as well as the keratan sulfate-chondroitin sulfate ratio seemed to increase proportionally to the articular cartilage depth. AB proteoglycan particles of various shapes (filament-like or leaf-like) and sizes (10 nm or 16-18 nm), depending on the articular cartilage depth and on the histochemical conditions (as above), were visualized in thin sections. Similar heterogeneity of elongated non-collagen particles was shown in replicas of fresh freeze-fractured and deep-etched specimens. An interpretation of the distribution and nature of articular cartilage proteoglycans was made by comparing the obtained morphological findings. PMID- 6242454 TI - The effect of agarose and dexamethasone on the nature and production of extracellular matrix components by elastic cartilage chondrocytes. AB - Chondrocytes isolated enzymatically from rabbit ear cartilage, were cultivated in vitro in the presence of 2% agarose or 0.1 mumol/l dexamethasone. Freshly isolated chondrocytes suspended in either Eagle's medium or 2% agarose were auto transplanted intramuscularly. Samples were then examined by light microscopy and transmission electron microscopy. The cells cultivated in vitro rapidly formed confluent multiple overlapping layers filled with a loose matrix consisting of single collagen fibres, proteoglycans and scarce elastic fibres. The number and maturity of the elastic fibres increased substantially after dexamethasone was added. The chondrocytes in intramuscular transplants produced a larger amount of intercellular matrix with many elastic fibres than those cultured in vitro. Addition of agarose to in vitro and in vivo systems selectively suppressed the elastin production but did not diminish the production of elastic fibre microfibrils and other matrix components. This made cultures and transplants of elastic chondrocytes resemble rather hyaline cartilage than the original tissue. It seems that the lack of elastin in the matrix does not result simply from inhibition of elastin secretion or increased elastolysis. It may be related to a reversible change of genetic expression of elastic cartilage chondrocytes under the influence of agarose. PMID- 6242455 TI - A biological and morphological comparison of cartilage cells in various kinds of lesions. AB - Cartilage is an important tissue, biologically and morphologically intermediate between connective tissue and bone. Much of the current knowledge on the biology of cartilage is still hypothetical, particularly that on the reproduction of mature cartilage cells. The existence of cartilage, and its formation, are dependent on certain conditions of metabolism, which for the most part differ strongly from those under which connective tissue or bone are produced, though these tissues are often closely related morphologically. One of the greatest problems in this field of human pathology is the total lack of correspondence between the micromorphology of most cartilaginous tumours and their biological properties, especially malignant proliferation. Thus cartilage lesions, particularly cartilaginous tumours, call for special, often unconventional methods, for even a superficial assessment. It appears that for evaluation of especially the biological properties of cartilage cells, the submicroscopic appearance of the nucleus is of special importance. A suitable model for the study of biological and morphological correlations of cartilage is the ossification of the cartilaginous skeleton, the appearance and existence of cartilage-cells in tissue cultures, and the behaviour of cartilaginous tissue under specific biomechanical conditions. PMID- 6242456 TI - The calcified-noncalcified cartilage interface: the tidemark. AB - Tidemark is an interface which may better be defined by biochemical methods than by morphology. It originates, by chondrocyte activity, between calcified and noncalcified cartilage layers of any kind, hyaline or fibrous, in areas exposed to either loading (joint) or pulling (insertion). In the articular cartilage it appears with skeletal maturation, in other localizations it is age-independent. It should be regarded as a special instance of a broader phenomenon of the calcification/mineralization front. Inside the joint cartilage its changes reflect the slow remodelling of the calcified layer and its inapparent shift towards the surface of the articular cartilage. In the marginal transitional zone of the joint, tidemark smoothly passes into the periosteum. Chondrocytes on both sides of the tidemark are positive for alkaline phosphatase and the positive reaction continuously goes on to the periosteum. PMID- 6242457 TI - Early response of cartilage to abnormal factors as seen in the meniscus of the dog knee after cruciate ligament section. AB - Ultrastructural changes in the medial meniscus of the knee were studied following section of the anterior cruciate ligament in 7 dogs. As compared with the contralateral control knee, collagen fibrils became abnormally widely spaced and disoriented from 1 month after operation and amorphous material on the (femoral) articular surface increased in thickness. In superficial cells, granular endoplasmic reticulum and Golgi membranes were more profuse and lipid droplets increased in number from 1 week. Both superficial and deeper cells were very active at 1 and 2 months after operation and the nuclear fibrous lamina had increased in thickness. Some cell degeneration occurred in the superficial zone from 1 month. At 15 months both matrix and cells appeared to have returned to normal. These changes are compared with those in articular cartilage after cruciate ligament section and with the effects of intravenous papain on cartilage. PMID- 6242458 TI - Quantitative morphological and biochemical investigations on the effects of physical exercise and immobilization on the articular cartilage of young rabbits. AB - The effects of physical exercise and immobilization on the knee joint articular cartilage of young rabbits (2.5 to 5 months of age) were investigated by quantitative histology, semiquantitative stereomicroscopy and scanning electron microscopy as well as biochemical methods, during a period of 8 weeks. Physical exercise increased the cell size in all zones of the uncalcified cartilage without notable concomitant change in the cell density. It also increased the volume density of the cells in the intermediate and deep zones. Increased striation of the cartilage surface was observed after 1 week's running period, suggesting superficial appearance of collagenous fibres and depletion of the proteoglycans on account of the exercise. However, after 4 to 8 weeks of running the increase of the striated surface was no longer significant. At the same time the proteoglycan content increased with preponderance of keratan sulfate-rich proteoglycans. Immobilization of the knee joint decreased slightly the cell size but increased the cell density in the superficial zone. Immobilization caused derangement of the smoothness of the articular surface already at the end of the 1st week with superficial splitting of the surface. Reduction of the cartilage matrix proteoglycans and collagen was observed after 1 week's immobilization. In the whole femoral surface, but not in the weight-bearing area of tibial lateral condyle, the proteoglycan content was replenished with chondroitin sulfate-rich molecules by the end of the 8th week after immobilization. Both physical exercise and immobilization caused significant intracondylar remodelling of the articular cartilage. PMID- 6242459 TI - Comparative assessment of articular cartilage and synovial membrane in experimental haemarthrosis. AB - The changes in articular cartilage and synovial membrane of the knee joints were studied in two groups of rabbits and Wistar rats with experimental haemarthrosis, electron microscopically. Hamarthrosis was produced in group 1 by a single autologous blood injection, in group 2 by intraarticular fracture of the femoral condyles. Samples were taken from the intact articular cartilage, the menisci and the infrapatellar portion of the synovial membrane 12 h to 20 days after intervention. Blood resorption occurs only in the synovial membrane. Fragmentation of erythrocytes and erythrocytophagy by synovial macrophages is documented. The different stages of intracellular digestion of erythrocyte fragments are traced down. Synovial fibroblasts do not participate in erythrocytophagy, although they disclose morphological signs of enhanced functional activity. The findings show changes in the matrix and chondrocytes within the articular cartilage and menisci, and presence of free erythrocytes and lipoprotein complexes amidst the collagen fibres of the matrix. The chondrocytes are poor in cell organelles, while the intracytoplasmic filaments, lipid droplets and glycogen granules are augmented in number. There is no evidence of erythrocytophagy by cartilage cells. On single blood injection in the joint, the ensuing changes are reversible, and the normal synovial membrane structure is restored much quicker than the articular cartilage. PMID- 6242460 TI - Changes in the cartilage proteoglycans in relation to age and osteoarthrosis. AB - Changes in the extracellular components of various connective tissues with time and continuous use, as well as within experimentally-induced and human pathological conditions, were studied by morphological, chemical and biochemical methods. Osteoarthrotic lesions were produced surgically by implantation of polyethylene sheets, by continuous compression of the knee joint, and by intraarticular papain injection. Results of the model experiments showed that, irrespective of the method used for the production of experimental cartilage lesions, the alterations are strikingly similar. Within connective tissues a gradual deterioration takes place, as measured by marked differences in the histological and histochemical patterns. The degradative changes occur primarily in the matrix, resulting in a significant decrease in proteoglycan content. Under conditions of stress, in young animals, chondrocytes seem to revert to the chondroblastic state, showing mitotic figures, and are capable of producing matrix much more rapidly than is normally seen. This increased activity might be regarded as a nonspecific "feed-back" response of cells, leading to a reparative normalization of the various destructive tissue alterations. PMID- 6242461 TI - Comparison of the nature and frequency of medical problems among patients in general, specialty and hospital dental practices. PMID- 6242462 TI - Dentistry and the handicapped--a persistent dilemma. PMID- 6242463 TI - Public assistance--general information for the dental practitioner. PMID- 6242464 TI - Wear in three different composite resins. PMID- 6242465 TI - Complement ligand-receptor interactions that mediate biological responses. PMID- 6242466 TI - Regulation of B-cell growth and differentiation by soluble factors. AB - The B-lymphocyte family of cells presents one of the most remarkable opportunities for the detailed study of regulation of growth and differentiation. Some members of this cell population have the property that they may be stimulated by ligand-receptor interactions, together with the sequential action of a series of lymphokines, to progress from the resting state, through several rounds of proliferation, and then to differentiate to immunoglobulin secretion. Other cells in this group participate in cognate cellular interactions with helper T cells in which the recognition of both antigen and a class II MHC molecule on the B-cell surface is key to activation. The differentiation of these cells is also controlled by soluble products. We have reviewed our developing knowledge of the biochemistry and mode of action of the lymphokines that act upon B cells. These include distinct growth and differentiation factors. Among these are the BCGFs of mice and humans and the various TRFs, which include molecules often described as differentiation factors. The next several years should witness major progress in understanding the physicochemical properties of the B cell specific factors, their time and nature of action, and the nature of their receptors. In addition, we can anticipate a major effort to understand the intracellular events that flow from the action of specific growth and differentiation factors that act upon B cells. Such information should lead to a new physiologically-based pharmacology for manipulation of antibody responses in human disease and in responses to vaccines. In addition, the fuller understanding of the nature and mode of action of the various growth and differentiation factors should make long-term growth of cloned B cells a procedure that can be routinely used in immunological laboratories for the precise study of the biology of responses by homogeneous populations of B lymphocytes. PMID- 6242467 TI - T-lymphocyte clones. AB - To date, the most successful uses of T-cell clones have been in the demonstration that a single type of cell can perform multiple functions. However, their potential usefulness is enormous, and the study of cell interactions using clonal populations has just begun. The development and study of more cloned populations will surely lead to a clearer analysis of cellular interactions in the immune system. The use of T-cell clones and hybridomas to analyze T-cell receptors and/or factors is well under way, and will continue to be an area of intense investigation. Molecular biologists will undoubtedly make more extensive use of T cell clones in the future, both as a source of cloning material and as transfection recipients. The most exciting area for development, from a medical point of view, is the potential for use of these cell lines or their products in immunotherapy and in providing a mechanism for specifically modulating the immune response. PMID- 6242468 TI - [Electrocardiographic picture of the left atrial involvement is independent of the form and consequence of atrial enlargement. Bidimensional echocardiographic study]. PMID- 6242469 TI - [Severe pulmonary arterial hypertension in a drug-addict: etiopathogenetic considerations]. PMID- 6242470 TI - Morphologic observations in coronary arteries, aortocoronary saphenous vein bypass grafts, and infant aortae following balloon angioplasty procedures. AB - Morphologic observations following transluminal balloon angioplasty are summarized from eight adult patients undergoing coronary or saphenous vein bypass graft angioplasty and from an infant with aortic valve stenosis angioplasty. Possible mechanisms of dilation injury and complications of balloon bursting are discussed. PMID- 6242471 TI - Coronary artery dissections. AB - Isolated spontaneous coronary artery dissections are rare and usually occur in women, the majority of whom are less than 40 years of age. Coronary artery dissection may also be caused by an extension of aortic dissection, especially in Marfan's syndrome. Iatrogenic coronary artery dissections are extremely rare, especially those secondary to coronary catheterization. The consequences of dissection may be fatal; therefore, early recognition and prompt therapy may be lifesaving. PMID- 6242473 TI - Effect of adaptation to a hot climate on the state of temperature reception. PMID- 6242472 TI - Cold vasodilatation in persons chronically exposed to low positive temperatures. PMID- 6242474 TI - Molecular weight characterization of virgin and explanted polyester arterial prostheses. AB - The macromolecular properties of 17 virgin commercial arterial prostheses and a series of explanted prostheses, both manufactured from poly(ethylene terephthalate) (PET) yarns, have been studied by gel permeation chromatography (GPC) and by differential scanning calorimetry (DSC). Only small differences were found between the average molecular weights and the degree of crystallinity of the unused reference grafts. A broadening of the DSC curves was observed for the prostheses containing texturized yarns compared with those made solely from flat, untexturized yarns. This broadening may be due to greater heterogeneity of the crystal sizes caused by the texturizing process and to the use of two or more different yarns with dissimilar thermal histories in the same prosthesis. Average molecular weights of the explant series were significantly lower than those of the corresponding reference grafts but almost time independent. The polydispersity index and the degree of crystallinity of the explants remained constant as a function of time. These results are discussed in regard to others available in the literature. PMID- 6242475 TI - Cytocompatibility of albuminated polyester fabrics. AB - An alternative to the usual technique of preclotting porous textile vascular prostheses prior to surgical implantation is to render them impermeable to blood by impregnation with a cross-linked albumin filler matrix. This material subsequently becomes the foundation for cellular development. The compatibility of such impregnated fabrics with newly formed endothelial cells has been evaluated by an in vitro organotypic culture method. This technique enables the characterization and numeration of cells that develop on blood contact surfaces and enables determination of their rate of development. Woven, knitted, and velour fabrics were evaluated following coating with albumin and either storage in Tyrode solution or 40% ethanol or desiccation by critical point drying. Preclotted cardiovascular repair fabrics prepared according to conventional surgical protocol served as controls. The identification of the newly formed cells was confirmed histologically. The most extensive and rapid cellular development was observed on the woven fabric and is believed may have resulted from the smoother surface topography of this substrate. Good cellular development was noted particularly on fabrics which had been stored in Tyrode solution. Ethanol had a deleterious effect on the apparent compatibility. PMID- 6242476 TI - Morphological characteristics of tendon cells cultured on synthetic fibers. AB - Filamentous carbon is currently being used as an implant material for tendon and ligament repair in humans. This material acts as a scaffold for the organization of new fibrous tissue growth. Primary cultures of rat tendon fibroblast cells (1 degrees RTF cells) were grown on carbon, Dacron, polyethylene and Nylon fibers in vitro. The morphological characteristics of these cells were examined. The process of cell migration from tendon explant to fiber substrate was similar for all four materials. Three morphological categories of cells were observed on these materials. (1) spherical dividing cells, (2) spindle-shaped migrating cells, (3) sheath-like migrating or stationary cells. The morphological characteristics and orientational behavior of cultured fibroblasts on these fiber materials were strongly influenced by the diameters of the fibers and by fiber surface characteristics such as longitudinal striations. The possible mechanisms of cell response to substrate geometric configuration are discussed along with the clinical significance of these experiments. PMID- 6242478 TI - An oriented phase-II trial of D-Trp6-LH-RH in patients with prostatic carcinoma. AB - An oriented phase II trial of D-Trp6-LH-RH was conducted according to Gehan's statistical method on 25 patients suffering from prostatic carcinoma. LH and testosterone serum levels decreased rapidly. Pain disappeared during the third month in 14 out of the 21 patients and markedly decreased in 5. Prostatism completely regressed in 10 out of the 22 subjects presenting it and markedly decreased in 9. Prostate hypertrophy regressed, as shown by ultrasonography, in 84% and by more than 50% in 37% of the patients. The overall regression rate of bone scintigraphy images was 43%; a regression of more than 50% was only registered in 12.5% of the patients; this may be explained by the long time which is necessary before bone image disappearance occurs. Prostatic acid phosphatase levels regressed in 75% and by more than 50% in 66.7% of the patients. PMID- 6242477 TI - Inhibition of the growth of some hormone dependent tumors by D-Trp6-LH-RH. AB - We have investigated the effects of chronic administration of D-Trp6-LH-RH on the growth of various hormone dependent tumors in rats and mice. Treatment of male Copenhagen F-1 rats bearing the Dunning R-3327H prostate adenocarcinoma with 25 micrograms of D-Trp6-LH-RH bid for 21 days significantly reduced tumor weight and volume as compared to controls. Serum LH, prolactin and testosterone levels in Copenhagen F-1 rats bearing Dunning tumors were significantly decreased after treatment with D-Trp6-LH-RH. Administration of D-Trp6-LH-RH in doses of 25 micrograms/day for 21 days to mice bearing the MXT mammary carcinoma significantly decreased tumor weight and volume. In rats bearing the MT/W9A mammary adenocarcinoma, D-Trp6-LH-RH, at a dose of 25 micrograms bid for 28 days significantly decreased tumor weight and volume. Administration of D-Trp6-LH-RH in a dose of 25 micrograms/day, 3-18 days after inoculation with the tumor, inhibited the growth of the prolactin (PRL) and ACTH-secreting pituitary tumor 7315a in female Buffalo rats. In three experiments D-Trp6-LH-RH (30-60 micrograms/day) decreased tumor weight and/or volume of the Swarm chondrosarcoma. Regression of these hormone-dependent tumors in rats and mice in response to chronic administration of D-Trp6-LH-RH suggests that this compound can be used for treatment of prostate cancer and breast cancer, and also considered for the development of a new endocrine therapy for chondrosarcomas, osteosarcomas, pituitary tumors and other hormone-dependent neoplasias. The demonstration of the successful use of LH-RH agonists for the palliative management of stage C and D prostate cancer has already shown that this treatment could be employed instead of surgical orchiectomy or estrogen therapy. Preliminary clinical trials suggest that agonists of LH-RH might also be of help in the treatment of breast cancer in premenopausal women. PMID- 6242479 TI - Nutrition and Down's syndrome. PMID- 6242480 TI - Down's syndrome: nutritional intervention. AB - Down's Syndrome patients are known to be of short stature, prone to infections, autoimmune disease, hypothyroidism, leukaemia, heart defects and later Alzheimer's disease. They tend to have older mothers, like Alzheimer's disease patients. The latter tend to have sibs with either Down's Syndrome or lymphoma/leukaemia. Evidence, looking at 28 Down's Syndrome patients, suggests that multiple food allergies, gluten-gliadin sensitivity or intolerance are causing a coeliac disease-like picture with a malabsorption state for essential vitamins, minerals and severe autoimmune disease. It is hoped that missed gluten gliadin sensitivity or intolerance with or without coeliac disease will be considered as a cause of abnormal oogenesis and spermatogenesis resulting in trisomy 21 and other aneuploidies. The mechanism most likely is low B1 interfering with sufficient release of cAMP for normal meiosis. Alternatively exorphins and peptides from foods may suppress prostaglandin E1 synthesis, or food sensitivities may alter toxic metal absorption mechanisms, which are thought to play a role in the development of Alzheimer's disease. Adequate vitamin/mineral supplementation, especially B1, prior to conception and in the first trimester is recommended for mothers at risk for DS, especially older mothers and a gluten free diet for those with coeliac disease or gluten-gliadin sensitivity/intolerance. Hopefully this will prevent conception of a DS child, or prevent heart defects/stigmata if one is conceived. DS children should be investigated for the above and commence a food allergy free diet with relevant supplements to meet their needs as early as maximum development. PMID- 6242481 TI - [Polymorphism of phosphoglucomutase in two breeds of West African cattle]. PMID- 6242482 TI - [Mucopolysaccharide measurement in Candida albicans infections of the oral cavity]. PMID- 6242484 TI - Involvement of the invertible G segment in bacteriophage mu tail fiber biosynthesis. AB - The orientation [G(+) or G(-)] of the invertible G segment of bacteriophage Mu DNA determines the host range specificity of the phage particles. In this study the hypothesis that the G segment genes are involved in synthesis of Mu tail fibers has been tested. Serum blocking power (SBP) assays demonstrated that among Mu late gene mutants only those defective in genes S or U encoded by the G segment were defective in G(+) SBP and that they lacked the same antigens. Electron microscopy of lysates produced by inversion-defective gin mutants (isolated by their inability to complement a hin inversion-defective mutant of the Salmonella phase variation segment) showed that G(+) phages with amber mutations in S or U made tail-fiberless particles with contracted tail sheaths. Inversion of G to the G(-) orientation or suppression of the amber mutations restored the normal phage particle morphology. These experiments demonstrate that genes S and U are required for Mu G(+) tail fiber biosynthesis and/or attachment. PMID- 6242483 TI - Rheumatoid non-lymphoid synovial cells and the induction of mixed leukocyte reactions. Low-density preparations containing Ia+ macrophages and dendritic cells are less stimulatory than peripheral blood non-T cells. AB - Interactions of autologous or allogeneic T cells with non-lymphoid synovial cells were investigated to study the mechanisms of T-cell activation in rheumatoid arthritis. The synovial cell fraction obtained by Percoll gradients contained an average of 31% cells positive for monocyte antigens and 62% intensely Ia-positive cells. Tissue cultures demonstrated large numbers of cells with a dendritic morphology. Mixed leukocyte reaction (MLR) cultures between these synovial cell preparations and autologous or allogeneic peripheral blood T cells as responder cells revealed low T-cell responsiveness with an average of 3900 dpm or 17 800 dpm, respectively, in contrast to 16 900 dpm or 79 600 dpm, using rheumatoid peripheral blood non-T cells (P less than 0.01), despite equivalent amounts of Ia antigens on both stimulator populations, as determined by cell-sorter analysis. The addition of indomethacin to these synovial cell/T cell co-cultures resulted in an enhancement of T-cell responsiveness; however, this increase did not reach statistical significance due to large test variations. Co-cultures of non lymphoid synovial cells and PHA-stimulated autologous T cells induced a marked inhibition of T-cell proliferation that could partially be reversed by the addition of indomethacin. The reduction of monocyte-antigen-positive cells by depletion of iron phagocytic cells did not result in a significant enhancement of T-cell responsiveness. These data demonstrate that the majority of non-lymphoid synovial cells, despite the presence of large amounts of Ia-antigens, are not potent inducers of T-cell proliferation and strong suppressing cells in polyclonal T-cell activation. These effects do not appear to reside in the macrophage fraction alone and can only partly be attributed to the action of prostaglandins. PMID- 6242485 TI - Tumorigenicity of adenovirus-transformed rat cells and expression of class I major histocompatibility antigen. AB - The expression of class I major histocompatibility antigens was studied in six syngeneic adenovirus 12 (Ad12)-transformed LIS rat cell lines of varying tumorigenicity. The concentration of MHC class I product was estimated by indirect immunofluorescence staining of viable cells in suspension with specific antibody and cytofluorographic analysis, and by sensitivity to killing by allogeneic cytolytic T cells (CTLs) elicited by immunization with spleen cells in vivo and in mixed lymphocyte reactions in vitro. None of the rat cell lines examined was devoid of MHC class I antigen. When compared to syngeneic Ad2 transformed cells or fibroblasts, the average intensity of fluorescence of Ad12 transformed lines was lower, suggesting that the concentration of MHC class I antigen is somewhat lower in Ad12-transformed cells. Sensitivity to killing by both in vivo and in vitro induced allogeneic CTLs, however, was not markedly lower with Ad12-transformed cells and correlation was not found between tumorigenic potential in vivo and sensitivity to allogeneic T-cell killing in vitro. PMID- 6242487 TI - [Studies on peripheral lymphocytes from patients with rheumatic fever and juvenile rheumatoid arthritis. Subpopulations of T-cells, B-cells, IgG-Fc receptor (+) cells and in vitro lymphocyte transformation to several mitogens]. PMID- 6242486 TI - An experimental study on immune complex induced arthritis in rabbits--reference to macrophages and M-type cells of the synovium. PMID- 6242488 TI - [M mode echocardiographic elements in the evaluation of left ventricular impedance in hypertrophic cardiomyopathy]. PMID- 6242489 TI - [Echocardiographic indications in the diagnosis of hypertrophic myocardiopathy. Diagnostic contribution of a retrospective study of 82 cases]. PMID- 6242490 TI - [Desmoid tumors (apropos of a clinical case)]. AB - The authors, starting from a case of desmoid tumour of abdominal wall, they had the opportunity to observe, discuss its possible etiopathogenetic factors, and confirm the validity of operation as the only therapy. PMID- 6242491 TI - Effectiveness of intensive care of very low birth-weight infants. AB - Perinatal/neonatal intensive care can be evaluated in terms of its efficacy, effectiveness and efficiency. There is good experimental evidence from randomized controlled clinical trials that intensive-care interventions in the perinatal period are efficacious in reducing perinatal/neonatal mortality and fetal/neonatal morbidity. The effectiveness of intensive care programs in large populations has not been tested experimentally. However, population surveys show that perinatal/neonatal mortality is declining and it is likely that this is due in large part to improved perinatal care. Moreover, low birth-weight infants born in Level 3 hospitals have a lower neonatal mortality rate than LBW infants born in hospitals that are less well staffed and equipped. The true size of the reduction in fetal/neonatal mortality that is attributable to perinatal interventions is difficult to estimate from the experience of referral hospitals because of selection bias (both postnatal and prenatal). Thus, the size of the reduction in mortality resulting from the intensive care of VLBW infants is quite striking in hospital-based studies, but more modest in area-based studies. The efficiency of perinatal interventions in reducing death and disability takes into consideration both the health outcomes and the costs attributable to perinatal intensive care. Although neonatal intensive care saves lives, it is doubtful that the rate of handicap in very low birth-weight infants has been much affected. The immediate and long-term costs of neonatal intensive care are high, but a systematic economic evaluation has not yet been published. PMID- 6242492 TI - Mouse trisomy 16 as an animal model of human trisomy 21: a new approach for studying the pathogenesis of Down syndrome. PMID- 6242493 TI - The history of Huntington's chorea. PMID- 6242494 TI - DNA and Huntington's chorea. PMID- 6242495 TI - Affective psychopathology in Huntington's disease: the Johns Hopkins hypothesis and German psychiatry. PMID- 6242496 TI - Argon-laser coagulation of the scleral spur (L.S.S.C.) in primary open-angle glaucoma and pigment glaucoma. PMID- 6242497 TI - Elderly men as caretakers of wives. PMID- 6242498 TI - [Arterial hypertension in childhood. The current panorama and its challenge]. PMID- 6242499 TI - [Theory and practice of functional orthodontic treatment in infants and young children with Down's disease]. PMID- 6242500 TI - [Contribution of experimental carcinogenesis to the pathogenesis of colorectal cancer in man]. PMID- 6242501 TI - [Acute spinal epidural infections due to common pathogens. 23 cases]. AB - Twenty-three cases of acute spinal epidural infection due to common pathogens were retrospectively studied. Pain is not always present initially and usually appears 15 to 32 days after the primary infection, which is only found in one half of the cases. When established, the condition is characterized by spinal rigidity, signs of infection, and compression of the cord or cauda equina. The diagnosis is confirmed by surgery, radiology (myelographic blockade, spondylodiscitis) or the finding of pus in the epidural space at lumbar puncture. A frequently delayed diagnosis explains the poor prognosis of these infections. Treatment should always include an antibiotic active against staphylococci, which are by far the most common pathogens. The indications for surgery are discussed in the light of published data compared to the authors' own experience. PMID- 6242502 TI - [Cancer of the thyroid in children. 14 cases]. AB - Fourteen cases of thyroid gland carcinoma in children (mean age: 10 years) were reviewed. Scintigraphy showed a cold nodule in 10 and diffuse heterogeneous uptake indicating undifferentiated carcinoma in 3. The clinical risk of these tumours resides in alterations of the thyroid gland and in lymph node involvement. The favourable long-term prognosis in children justifies a conservative surgical treatment. Pulmonary metastases respond well to radioactive iodine. TSH secretion must be completely suppressed by continuous hormonal treatment. Anticancerous irradiation is fraught with potential dangers. PMID- 6242503 TI - [Changes in plasma prostaglandins in normal subjects in an orthostatic position. Comparison with the response of the renin-aldosterone system]. AB - Changes in blood pressure, plasma concentrations of PGE2, PGF2 alpha, G-keto-PGF1 alpha, thromboxane B2, aldosterone and plasma renin activity were evaluated in 13 normotensive subjects passing from supine to upright position. Orthostatism resulted in slight elevation of blood pressure and increase of all plasma prostaglandins (except PGE2), plasma aldosterone and plasma renin activity. A positive correlation was found in supine position between systolic arterial pressure and thromboxane B2 level (p less than 0.001). In upright position, however, blood pressure did not correlate with any of the hormones assayed. Orthostatism is a powerful stimulant of renin and aldosterone secretion but not so much of prostaglandin secretion. Basal arterial pressure is significantly influenced by thromboxane A2. PMID- 6242504 TI - [Contribution of iodinated cisternography to craniocerebral computed tomography]. AB - Computerized tomography is usually adequate to explore supratentorial lesions of the skull and brain. However, it is often inadequate for a detailed analysis of lesions of the base of the skull and their anatomical rapports. Opacification of the subarachnoid spaces by means of a contrast medium (computerized cisternography) has proved extremely useful in such cases. The contrast media utilized are tri-iodized, water-soluble compounds which are well tolerated. The technique and anatomical data of the method are described, and its applications in different fields of tumoral and non-tumoral pathology are discussed. PMID- 6242505 TI - [Chemotherapy of isolated hepatic metastases. Use of a subcutaneous reservoir for intra-arterial infusions]. PMID- 6242506 TI - [Shock following periarticular infiltration of methylprednisolone acetate]. PMID- 6242507 TI - [Acute sinoatrial deficiency in a hypertensive patient under treatment. Role of indomethacin]. PMID- 6242508 TI - [Can inapparent food intolerance play a role in lipoid nephrosis?]. PMID- 6242509 TI - [Isolated papilledema during anticoagulant treatment. Rapid recovery after withdrawal of fluindione]. PMID- 6242510 TI - [Echographic thickening of the gallbladder wall in a child. Adverse effects of umbilical catheterization]. PMID- 6242511 TI - [Association of Vogt-Koyanagi disease, Gougerot-Sjogren syndrome and erythema nodosum]. PMID- 6242512 TI - [Angioplasty of renal arteries in the treatment of renovascular hypertension. Our experience in 63 cases]. AB - Percutaneous transluminal angioplasty for treatment of renovascular hypertension was performed on 63 patients during a 5 years period. No compliance related to this procedure set in. At follow-up, the clinical results were shown to be positive in 85.7% of the cases. PMID- 6242513 TI - [Strategy for the use of hepatitis B vaccine in the United Kingdom, France and Italy]. PMID- 6242514 TI - [The nucleus of the cardiac myocyte in ventricular hypertrophy. Ultrastructural study]. AB - This study reports the nuclear alterations during ventricular hypertrophy of human heart. The nuclear length is increased while its diameter remains normal. A large spectrum of morphological alterations was observed: increased foldings and convolutions of the membrane; irregular shape of the nuclei, some of them being dumbbell-shaped; intranuclear pseudo-inclusions; intranuclear tubules. These alterations are related to excessive synthesis of membrane during nuclear growth. PMID- 6242515 TI - [Proceedings of our studies on cellular immunity]. PMID- 6242516 TI - Enterotoxigenic Staph aureus of different phage groups as seen in Manipal. PMID- 6242518 TI - Realtime bloodflow imaging system utilizing auto-correlation techniques. PMID- 6242517 TI - [Treatment of prostatic cancer]. PMID- 6242519 TI - Doppler spectral broadening and anomalous vessel wall movement in the study of atherosclerosis of the carotid arteries. AB - In this paper the hypothesis is presented that a combination of Doppler spectral broadening techniques with quantification of the relative movement between the atherosclerotic plaque and the artery wall can be used to investigate the development and progression of the plaque. PMID- 6242520 TI - Non-invasive and quantitative measurement of volume flow-rate at internal and external carotid and vertebral arteries. AB - A non-invasive and quantitative system to measure the volume flow-rate, velocity and diameter in the internal and external carotid arteries and vertebral artery was developed. It was verified from the model experiment and clinical applications that this system could provide quite useful flow informations in small and sinuous artery within 8% error. PMID- 6242521 TI - Application of statistical techniques to data obtained from Doppler ultrasound examination of the extracranial arteries. AB - Techniques of increasing sophistication are being used to analyse the data obtained from continuous wave Doppler Ultrasound examination of patients with suspected arterial disease in the extracranial circulation. This study was carried out in order to compare the results of using relatively simple parameters such as the A/B ratio and the Index of Circulatory Resistance, ICR, and more recent techniques such as Principal Component Analysis on the changes apparent in the common carotid arterial waveform, particularly in the presence of disease in the internal carotid artery. This information was obtained from patients undergoing angiography so that the Doppler ultrasound results could be compared directly with an invasive assessment of the arteries under study. The signals obtained were processed off line using a Kay Sonograph Spectrum Analyser. The resulting maximum frequency envelope was further processed using a statistics package on a 2970 ICL computer. The A/B and ICR values were calculated manually. The preliminary results, calculated from 105 comparisons between Doppler ultrasound and angiography, suggest that techniques, such as Principal Components Analysis, are best able to cope with the waveform changes obtained in this study. PMID- 6242522 TI - Evaluation of cerebral blood flow in the normal neonate by Doppler spectrum analysis. AB - Continuous wave Doppler ultrasound has seldom been applied to the evaluation of the cerebral circulation of the newborn infant. Twenty-five term infants were studied and records taken from the common carotid and anterior cerebral arteries during the first week of life using a bidirectional Doppler instrument. The best Doppler signals obtained were audiofrequency analysed and sonagrams recorded. Analysis of the carotid sonagrams revealed a mean Pulsatility Index (PI) on the first day of life of 0.98 compared to 0.88 on Day 2 (p less than 0.001). An unexpected finding was the absence of continuous carotid blood flow in the majority of infants in the first hours of life. The PI on subsequent days did not differ significantly from Day 2. The PI of the anterior cerebral arteries on Day 1 was significantly elevated (p less than 0.001) compared to Day 2 and subsequent days. The significance of these findings and their importance in the further evaluation of pathological cerebral states in the neonate, especially birth asphyxia and intracranial haemorrhage are discussed. PMID- 6242523 TI - Doppler waveform analysis and percutaneous dilatation of arteries in ischaemia of the lower limb. AB - Percutaneous transluminal dilatation of narrowed atheromatous arteries using the inflatable Gruntzig catheter is becoming an accepted non-surgical treatment for patients with disabling intermittent claudication of the lower limb. The use of doppler ultrasound to study limb blood flow in a group of patients having aortic or iliac dilatation is described. PMID- 6242525 TI - An objective feature extraction technique applied to the Doppler waveforms from the groin: a prospective study. AB - A group of 80 patients presenting with lower limb ischaemia were classified according to their arteriographic findings. The maximum frequency envelope from the Doppler waveforms obtained from the common femoral artery were retrospectively analysed using a mathematical feature extraction technique, principal component analysis (PCA). Two of the three coefficients uniquely describing each waveform were plotted and classified according to their arteriographic groupings. The best separating planes were then defined. Twenty eight new patients were subsequently prospectively assessed using the principal components and separating planes defined in the previous study. The results were compared with the arteriographic findings and showed that PCA represents a significant improvement in diagnostic accuracy when compared with other techniques. PMID- 6242524 TI - Differential diagnosis of arterial disease of the lower limb using Doppler ultrasound. AB - Doppler arterial waveforms from the femoral and ankle arteries of 55 normal control subjects and 76 arteriopaths were analysed for Laplace transform coefficients, delta and omega omicron, and pulsatility index (PI). At the femoral artery delta was superior to PI in accurately detecting mild and moderate aortoiliac stenosis, as assessed from arteriograms. In the femoropopliteal segment, the ratio of omega omicron from femoral to ankle level compared favourably with PI damping factor in the detection of occlusive disease. The Laplace transform system provides a helpful diagnostic method in lower limb arterial disease. PMID- 6242526 TI - Studies of the blood flow pattern in the left and right ventricular outflow tract using pulsed Doppler echocardiography. AB - In this paper, we reported that the main blood flow velocity in the LVOT and RVOT manifests characteristic variations with Doppler echocardiography. The volume over-load in the right heart changed the blood flow velocity pattern and the site of peak velocity in RVOT. And then, that in the left heart changed the blood flow velocity pattern and the site of peak flow in LVOT. We found a small "a" wave, which caused Ia on PCG can be recognized in LVOT during the isovolumic contraction phase. The small "a" wave and "a/H" ratio are useful criteria for detecting the changes of left ventricular contractility. There were linear correlate plot between EDP or peak-dP/dT and "a" or "a/H" in cases of HCM and IHD significantly. PMID- 6242527 TI - Detection and analysis of blood flow in aortic dissection with two-dimensional echo Doppler technique. PMID- 6242528 TI - New approach to noninvasive assessment of blood flow in the major arteries in the abdomen by two-dimensional Doppler echography. PMID- 6242530 TI - Population genetic studies of PI, Tf, Gc and PGM1 subtypes among various caste groups in North India. AB - Approximately 500 blood samples from various endogamous groups in north India have been subjected to isoelectric focusing to reveal genetic variation at the PI, Tf, Gc and PGM1 loci. The average heterozygosity per locus varies from 40% to 60% and the gene frequency data reflects considerable variation among the caste groups studied. The Nei genetic distances calculated from the 4 loci demonstrate that Khatri, Arora and Rajput are strongly clustered together and genetically they are closer to Brahmin than to Vaish and Scheduled Castes. Vaish emerge as a unique group showing maximum genetic distances with all other caste groups. The comparison of the present populations with our own data from two south Indian populations indicates that the tribal population of Soliga is distinct from the non-tribal populations, but the non-tribal south Indian series clusters closely with the main caste populations in north India. PMID- 6242529 TI - Analysis of the portal vein flow with two-dimensional echo-Doppler method. AB - Blood flow of the portal vein was non-invasively studied in healthy and diseased humans with the combined use of the ultrasonic pulsed Doppler technique and real time two-dimensional echography. In addition, the influence of food intake to the portal flow was assessed. PMID- 6242531 TI - Typology of the respiratory muscles in normal men and in patients with moderate chronic respiratory diseases. AB - Histochemical muscle fibre composition was studied in biopsies from the diaphragm, the external and internal intercostal muscles in the fifth intercostal space and horizontal and vertical parts of the serratus in 8 subjects with normal lung function and in 18 patients with abnormal lung function (6 restrictive and 12 obstructive). Muscle fibres were classified as type I (slow twitch) or type II (fast twitch) on the basis of their myofibrillar ATPase pH lability. All the muscles studied showed a mosaic pattern with the two fibre types. In every respiratory muscle, the percentage of type I fibres was higher than 50%. There was no significant difference between the three groups (normal, restrictive and obstructive) for each of the six muscles studied. The fibre diameters were similar for all types and muscles (range of means: 41-63 micron), except for the diaphragm in which the diameters of type I and type II fibres were significantly higher in the normal subjects as compared to the obstructive and restrictive patients. Moreover, there was a significant linear correlation between the diameter of the diaphragmatic fibres and vital capacity and FEV1. A low "atrophy factor" was found for each muscle studied with a large intra-individual variation. The results support the idea that the increased respiratory loading due to disease do not hypertrophy the respiratory muscles and suggest that the effect of the disease on the respiratory muscles is more related to the increased mechanical impedance of the respiratory system rather than to the changes in thoracic configuration. PMID- 6242533 TI - [Production of anti-idiotypic monoclonal antibodies that recognize the receptor for murine gamma interferon]. AB - In this work we consider the possibility to produce a monoclonal antibody against murine interferon gamma receptor using an approach based on the anti-idiotypic network theory of Jerne. We have found a rat monoclonal antibody (C-28) directed against the combining site of AN-18, a rat monoclonal antibody neutralizing murine interferon gamma activity, that is able to bind interferon receptor. PMID- 6242532 TI - Psychosomatic dermatology. PMID- 6242534 TI - [Antibiotic susceptibility and phage typing of Staphylococcus aureus isolated from healthy carriers]. PMID- 6242535 TI - [Cytotoxicity mediated by T lymphocytes. Current status in humans]. PMID- 6242536 TI - [First-trimester fetal diagnosis of alpha-thalassemia]. PMID- 6242537 TI - [Genome cloning of the vaccinia virus, Tiantan strain]. PMID- 6242538 TI - [Studies on expression of the human IFN-alpha D genome in mouse L cells]. PMID- 6242539 TI - [Studies on the mechanism of antitumor action of Dian III]. PMID- 6242540 TI - [Effects of diamines and their derivatives on ornithine decarboxylase activity in mouse sarcoma 180 in vivo]. PMID- 6242541 TI - [Biosynthesis of CPSI from the liver of normal rats and and diethylnitrosamine fed rats in rabbit reticulocyte lysate cell-free system]. PMID- 6242543 TI - [Inhibitory action of retinoic acid and N-(4-carboxyphenyl)-retinamide on the biosynthesis of DNA, RNA and protein in Ehrlich ascites carcinoma]. PMID- 6242542 TI - [Studies on mechanism of the antiplatelet effect of sodium ferulate--effect on TXA2/PGI2 balance]. PMID- 6242544 TI - [Histofluorescence changes in noradrenaline of rat tissue due to the effect of E. coli endotoxin]. PMID- 6242545 TI - [Heritable translocation assay in mice after prolonged and TEM treatment]. PMID- 6242546 TI - [Animal reservoirs of epidemic hemorrhagic fever--experimental studies and identification of the specificity of rat lung antigens. Cooperative Research Group for Epidemic Hemorrhagic Fever]. PMID- 6242547 TI - [Clinical manifestations of the reactive immunoblastic proliferation of lymph nodes]. PMID- 6242548 TI - [Studies on SCE frequencies in peripheral blood lymphocytes with a HOAP regimen]. PMID- 6242549 TI - [One-stage reconstruction of the penis with a composite iliac crest and lateral groin skin flap]. PMID- 6242550 TI - [Prevention and treatment of DIC complicating Wirstroemia chamaedaphen Meisn. administration for mid-term labor induction]. PMID- 6242551 TI - [Observation on the effect of dietary instruction for diabetes mellitus at an outpatient clinic]. PMID- 6242552 TI - [Method for measuring the pulmonary artery pressure with a right cardiac catheter in rats]. PMID- 6242553 TI - [A simple and rapid method for concentrating influenza viruses]. PMID- 6242554 TI - [Application of spline function in biomedical research]. PMID- 6242555 TI - Abnormalities of fibrinolysis in essential hypertension. AB - A highly-standardized plate method was used to study fibrinolytic profiles in 14 patients with essential hypertension and 245 normotensive healthy control subjects. Compared with the normotensive group, the group with essential hypertension showed a defect in fibrinolysis, as evidenced by a significant increase in the mean level of inhibitor of plasminogen activation, and a subset of the hypertensive patients also showed a significant decrease in the mean level of vascular plasminogen activator. There were no significant differences between the two groups in relation to plasma fibrinogen level, total fibrinolytic activity and plasmin inhibitor. The alterations in inhibitor of plasminogen activation and vascular plasminogen activator in the patients with essential hypertension may reflect a defect in the fibrin-clearing mechanism and, perhaps, contribute to the vascular complications of hypertension. PMID- 6242556 TI - Natriuretic response to atrial natriuretic factor enhanced by angiotensin II and vasopressin. AB - The effect of angiotensin II (ANG II) and arginine vasopressin (AVP) on the natriuretic response to partially purified high molecular weight atrial natriuretic factor (ANF) was examined in anaesthetized rats. ANG II and AVP were infused continuously at equipressor doses. Rats receiving ANG II and AVP showed five- to sevenfold greater natriuretic responses to bolus injections of ANF than controls. A significantly smaller augmentation of the natriuretic response to ANF was produced by equipressor does of norepinephrine and epinephrine, suggesting that the potentiation by ANG II and AVP were not entirely due to increased mean arterial pressure (MAP). Decreased MAP in rats receiving infusions of saralasin and hydralazine did not diminish the natriuretic response to ANF. The results suggest that the ANG II and AVP augmentation of the ANF-induced natriuresis is mediated partly through increased MAP and partly by interacting with the renal action of ANF. PMID- 6242557 TI - Atriopeptins: bioactive peptides derived from mammalian cardiac atria. AB - Mammalian atria possess bioactive peptides that are natriuretic-diuretic and potent relaxants of vascular and nonvascular smooth muscle. Characterization of the biological activity of rat atrial extracts indicates two major peaks, having apparent molecular weight of 20,000-30,000 (atriopeptigen) and less than 10,000 (atriopeptins). The amino acid sequence of atriopeptins I, II and III have been determined, and it has been found that their structures are only slightly different. Atriopeptin I (twenty-one amino acid residues); ser-ser-cys-phe-gly gly-arg-ile-asp-arg-ile-gly-ala-gln-ser-gly-leu-gly- cys- asn-ser) relaxes intestinal but not vascular smooth muscle strips, and is natriuretic. Atriopeptins II and III (23 and 24 residues; the 21-sequence of I with the addition of phe-arg or phe-arg-tyr at the C-terminus, respectively) relax intestinal and vascular smooth muscle strips and are potent natriuretics. Since atriopeptigen and the atriopeptins exhibit similar biological effects the possibility of a precursor-product relationship was tested. Mild proteolytic digestion (1IU/ml trypsin) of atriopeptigen activates this peptide and reduces its apparent molecular weight. Examination of whether the atria of Krebs perfused isolated hearts released the bioactive atrial peptides revealed the presence in the cardiac effluent of a trypsin-labile substance that was natriuretic-diuretic and a smooth muscle relaxant. To determine which form of the atrial peptide (e.g. atriopeptigen or atriopeptin) is released by the atria the cardiac effluents were concentrated and partially purified. The cardiac effluent contained a substance(s) similar to atriopeptin, but did not appear to possess the less active high molecular weight peptide, atriopeptigen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 6242558 TI - Antihypertensive and aldosterone-lowering effects of synthetic atrial natriuretic factor in renin-dependent renovascular hypertension. AB - A 24-amino acid residue synthetic atrial natriuretic factor (ANF) antagonizes angiotensin II-induced vascular contractility and aldosterone production in isolated blood vessels and adrenal cells, respectively. To determine the significance of these effects in vivo, the blood pressure and aldosterone responses to synthetic ANF were evaluated in rats with two-kidney, one clip hypertension (n = 5) and in sham-operated controls (n = 4). In the latter, ANF caused a slight fall in mean blood pressure (-7 +/- 3%) and inconsistent changes in plasma renin and aldosterone. In hypertensive rats, ANF decreased blood pressure by 31 +/- 7 mmHg (17 +/- 3%), comparable to the effect of the angiotensin antagonist saralasin (31 +/- 4 mmHg). Plasma renin activity increased from 48 +/- 15 to 79 +/- 23 ng/ml/h. Despite this, ANF caused marked suppression of plasma aldosterone (from 97 +/- 28 to 20 +/- 8.9 ng/100 ml). These results show that ANF can exert potent antihypertensive and aldosterone-lowering effects in vivo, at least when the renin-angiotensin system is stimulated. PMID- 6242559 TI - Atrial natriuretic factor: purification of active peptides, cloning of cDNA and determination of structures of active peptides and precursors. AB - Four peptides possessing both natriuretic and smooth muscle relaxant activities were purified from rat heart atrium and their amino acid sequences were determined. All contained a common sequence which contains a macro-ring structure formed by 17 amino acid residues and a disulphide bridge. The major atrial peptide in the atrium was identified as that containing 31 amino acid residues. The cDNA of the atrial peptide precursor was cloned and its nucleotide sequence determined. The amino acid sequence of the precursor deduced from the nucleotide sequence contained 152 residues and a potential signal peptide sequence characteristic of secretory polypeptides. PMID- 6242560 TI - Human atrial natriuretic polypeptides (hANP): purification, structure synthesis and biological activity. AB - In the present survey for natriuretic factors in human atrial extract, conducted by using in vitro assay for the relaxant activity of chick rectum, three distinct human atrial natriuretic polypeptides (hANP) (alpha-, beta- and gamma-hANP), differing in molecular weight (alpha, 3000; beta, 6000, gamma, 13 000 daltons) have been purified and sequenced. gamma-hANP, of 13 000 daltons, has been identified as a 126-residue peptide which carries the whole sequence of alpha hANP of 28-amino acids at the C-terminus, while beta-hANP has been proved to be an antiparallel dimeric form of alpha-hANP. Synthetic alpha-hANP at a dose of 0.2 nmol induces diuresis and natriuresis as well as hypotension, when injected into assay rats [1]. Natriuretic activity of beta- and gamma-hANP was estimated to be about one-fifth or less on molar base than that of alpha-hANP. PMID- 6242561 TI - Characterization of synthetic atrial natriuretic factor: vasodilator profile and decreased vascular sensitivity in hypertensive rats. AB - Synthetic atrial natriuretic factor (ANF) relaxed agonist-induced tone in rabbit aortic rings as well as intrinsic, myogenic contractions in the isolated rabbit facial vein (IC50s = 0.1 to 5 nM). Tissues depolarized by high levels of K+ were refractory to ANF. A similar profile was obtained with extracts of rat atria and with sodium nitroprusside (NaNP) but not other vasodilators. Aortas from spontaneously hypertensive rats (SHR) were significantly less sensitive to the relaxant effects of ANF (and NaNP) than were aortas from Wistar-Kyoto (WKY) rats. However, atrial extracts from SHR were more effective than WKY rat atrial extracts in relaxing normotensive aortic rings. Radioimmunoassay analysis confirmed a small increase in ANF immunoreactive material in SHR compared with WKY rat atria. The similar vascular profile for both ANF and NaNP suggests that these agents share a common mechanism of action. A reduced end organ responsiveness in SHR may lead to an increased atrial content of ANF in these animals. PMID- 6242562 TI - Biochemical alterations in cardiac hypertrophy. AB - In both two-kidney, one clip renal hypertensive rats (RHR) and spontaneously hypertensive rats (SHR) with myocardial hypertrophy, inotropic responsiveness to adenylate cyclase mediated agonists, such as isoproterenol and glucagon is decreased, as is the responsiveness to phenylephrine acting via alpha 1 adrenergic receptors. However, defects in the excitation response pathway differ in the two hypertensive models. In SHR beta-adrenergic receptors are decreased, alpha 1 receptors increased, cyclase activity is unchanged but c-AMP stimulated protein kinase is decreased. In RHR beta-receptors are increased, alpha 1 receptors decreased, adenylate cyclase activity decreased due to decreased nucleotide regulatory protein activity, and microsomal cAMP stimulated protein kinase is increased. We conclude that, although functional changes in hypertensive cardiac hypertrophy are similar, the underlying biochemical alterations are different. The shift in balance between alpha- and beta adrenergic pathways may be a compensatory mechanism and play a role in the pathophysiology of cardiac hypertrophy. PMID- 6242563 TI - Vasopressin induces endothelium-dependent relaxations of cerebral and coronary, but not of systemic arteries. AB - Vasopressin causes relaxations of isolated basilar and left circumflex coronary arteries of the dog. After removal of the endothelium the inhibitory effect of vasopressin is abolished in the basilar and reduced in the coronary arteries. By contrast, vasopressin causes contractions of femoral arteries, which are not affected by the removal of endothelium. Indomethacin, nordihydroguaiaretic acid, atropine, propranolol and cimetidine do not reduce the inhibitory effect of vasopressin in basilar arteries. However, the V1-vasopressinergic antagonist d(CH2)5Tyr(Me)AVP blocks the vasopressin-induced relaxations, indicating that the effect of the hormone on the endothelium is mediated by activation of specific V1 vasopressinergic receptors. PMID- 6242565 TI - Effect of prolonged exercise on plasma catecholamines. PMID- 6242564 TI - Immunoregulatory factors in pregnancy: essential or irrelevant in the maintenance of the fetoplacental allograft? PMID- 6242566 TI - An unusual case of fatal macrophagic pneumonia in a 12-days old infant, caused by a gram-negative Legionella-like microorganism. PMID- 6242567 TI - Pulmonary adiaspiromycosis of some free living small mammals in the north Moravian region: pathologic findings and experimental-biological observations. PMID- 6242568 TI - The role of various factors in the appearance and in further development of myocardial lesions. PMID- 6242569 TI - [Fatty tissue necrosis of the breast with ring calcifications]. PMID- 6242570 TI - Crohn's disease, serum immunodepressive factors and circulating immune complexes. PMID- 6242571 TI - [The prognosis for children with cardiomegaly]. PMID- 6242572 TI - Effect of bioclimatological factors on the origin of myocardial infarction. PMID- 6242573 TI - Partial epiglottectomy. PMID- 6242574 TI - The scalogram of the school-achievement test. PMID- 6242575 TI - [Histogenesis of the heart conduction system in human embryos and fetuses. The differentiation of the atrioventricular (His) bundle]. PMID- 6242576 TI - Monte Carlo verification of the scalogram model. PMID- 6242577 TI - [Cerebrospinal fluid findings in encephalomalacia]. PMID- 6242578 TI - [Cerebrospinal research in the diagnosis of encephalomalacia]. PMID- 6242579 TI - [Myocardial lesion in collagen diseases]. PMID- 6242580 TI - Diffuse carcinomatosis of the spine and neurocranium. PMID- 6242581 TI - [Coincidence of 2 different brain tumors]. PMID- 6242583 TI - [Ultrastructure of the cellular elements in the internodal junctions of the heart conduction system in human embryonic and fetal hearts]. PMID- 6242582 TI - [Interactions of antiepileptics]. PMID- 6242584 TI - [Initial results of the determination of HDL-cholesterol in patients with cerebrovascular strokes and multiple sclerosis (the significance of the ratio between HDL-cholesterol and total cholesterol)]. PMID- 6242585 TI - [Abnormal values of the immunological parameters in dystrophia myotonica. The results of complex research on the members of 3 generations of a family]. PMID- 6242586 TI - Biochemical analysis of articular environment in diseases of motor apparatus. PMID- 6242587 TI - Development of the conduction system of human embryonic and fetal heart: differentiation of internodal connection. PMID- 6242588 TI - Some methodical aspects of the evaluation of anti-inflammatory drugs in experimentally induced oedemas of the rat hind paw. PMID- 6242589 TI - Tissue distribution of chloroquine and hydroxychloroquine in rats. PMID- 6242590 TI - Proof of calcium in rat testicles after single and repeated ischemia. PMID- 6242591 TI - Electron microscopic study on the development of hydronephrotic changes in the kidney of rabbit. PMID- 6242592 TI - Experimental hydronephrotic atrophy of the kidney in light microscopy. PMID- 6242593 TI - Simple synthesis of (leucine5)-enkephaline. PMID- 6242595 TI - Chemical analysis of inorganic components in human submandibular calculi. PMID- 6242594 TI - Determination of antioxidants of the diphenylamine type in butadiene-styrene rubber (BSR). PMID- 6242596 TI - Changes in leukocyte level in peripheral blood after destruction of mammillary nuclei of the hypothalamus. PMID- 6242597 TI - Objective evaluation of analgesic effect of drugs in laboratory animals by a new methodological approach. PMID- 6242598 TI - Demonstration of mitogenic and antimitotic factors in human serum using chicken embryos as testing system. PMID- 6242599 TI - 85 years of the hospital "Na Tabulovem vrchu" and 35 years of its change into a faculty hospital. PMID- 6242600 TI - [Angiocardiographic demonstration of PFC (Persistent Fetal Circulation) syndrome in 7 newborn infants]. PMID- 6242601 TI - Our experiences with X-ray diagnosis of renal pseudotumours. PMID- 6242602 TI - Present state and possibilities of the medical use of chlorococcal algae. PMID- 6242603 TI - Application of communist education in medicine, in particular in psychiatry. PMID- 6242604 TI - Teaching and organization of legal medicine in Czechoslovakia. PMID- 6242605 TI - Reflection of changes in level of excitability of the central nervous system under stress in some physiological functions of an organism. Review. PMID- 6242606 TI - [Problems in team work in the health system from the viewpoint of responsibility]. PMID- 6242607 TI - The problem of human geohelminthoses and the prospects for their biological control. PMID- 6242608 TI - Number of unknown and incorrectly answered questions in a set of tested subjects. III. PMID- 6242609 TI - Verification of the assumption of independence and identical distribution of responses in the record of the school-achievement test. I. PMID- 6242611 TI - Verification of the assumption of independence and identical distribution of responses in the record of the school-achievement test. II. PMID- 6242610 TI - Thirty-five years of the Faculty of Medicine at the reestablished University in Olomouc. PMID- 6242613 TI - Ultrastructural changes of neurons in the spinal cord of hibernating bat. PMID- 6242612 TI - Entropy relations in the variables of the school-achievement test. PMID- 6242614 TI - Antimitotic effect of serum from patients with digestive tract cancer on equivalent chicken embryo tissues. PMID- 6242616 TI - Immunoglobulin D determination in healthy population and in some pathological conditions. PMID- 6242615 TI - Increased serum lysozyme as a marker of intestinal disorders with presumed immunological background. PMID- 6242617 TI - [Oxygenation curves in enzymopathic hemolytic anemias]. PMID- 6242618 TI - Experimental uveitis in rabbits induced with BSA and horseradish peroxidase. PMID- 6242619 TI - [Knowledge of group psychotherapy in the Psychiatric Clinic in Olomouc]. PMID- 6242620 TI - Controlled thermolysis of spinal ganglion for relief of intractable metameric pain. PMID- 6242621 TI - Molecular mechanisms of the biological activity of quaternary benzophenanthridine and protoberberine alkaloids. PMID- 6242622 TI - Nonesterified fatty acids in the brain structures--the effect of convulsive activity. PMID- 6242623 TI - The effect of antiepileptic drugs on nonesterified fatty acids in the brain structures during convulsive state. PMID- 6242625 TI - The hundred-point test lattice of rectangular shape with hexagonal point distribution for volumetry. PMID- 6242624 TI - School-achievement test in evaluation of the students' knowledge of the antibiotic therapy. Comparative study. PMID- 6242626 TI - [Scanning electron microscopic research on the stapes. Characteristics of the structure of its head, neck and crura]. PMID- 6242627 TI - The relation between proteolytic activity and ovicidal activity of mutants of Verticillium chlamydosporium. PMID- 6242628 TI - Morphological changes in myocytes of rats exposed to local irradiation of the head with supralethal doses. PMID- 6242629 TI - Chemotaxonomy of plants of the genus Papaver L. XCI. PMID- 6242630 TI - Morphological changes of the coronary arteries of rats with their heads irradiated with supralethal doses. PMID- 6242631 TI - [Effect of morphine on the white blood cells]. PMID- 6242632 TI - Vegetative segregation and arthrosporogenesis in Trichophyton mentagrophytes. PMID- 6242634 TI - [A new hypothesis on the immune surveillance of tumors]. PMID- 6242633 TI - Nonspecific alpha-naphthyl acetate esterase (ANAE) as a T-lymphocyte marker in rabbits. PMID- 6242635 TI - [Functional interpretation of lymph node reactions]. PMID- 6242636 TI - [Current status and potentials of chromatographic methods in drug determination in biological material]. PMID- 6242637 TI - Isoquinoline alkaloids in local periodontal disease therapy (preliminary notice). PMID- 6242638 TI - Vitamin A level in patients with chronic periodontal disease. Preliminary notice. PMID- 6242639 TI - Contribution to indication of total therapy with vitamin E in chronic periodontal disease (pilot study). PMID- 6242640 TI - Immunosuppressive therapy of experimental uveitis. PMID- 6242641 TI - The effect of corticosteroids on experimental uveitis. PMID- 6242642 TI - Application of N-acetylamino-6-hexanoic acid in osteosynthesis of open fractures. PMID- 6242643 TI - Environmental control of sporogenesis in Trichophyton mentagrophytes. PMID- 6242644 TI - [Residual lung volumes in patients with acute myocardial infarct]. PMID- 6242645 TI - [Nitroglycerin in patients following acute myocardial infarct]. PMID- 6242646 TI - The clinical spectrum of thrombocytosis. PMID- 6242647 TI - Orientational examination schema of interoreflex (autonomic) functions. PMID- 6242648 TI - Mutual relations of some interoreflex (so-called autonomic) and psychological parameters. PMID- 6242649 TI - Tetanic syndrome during year seasons. I. Ischemic and hyperventilation tests. PMID- 6242650 TI - Tetanic syndrome during year seasons. II. Stimulation electromyography. PMID- 6242651 TI - [The place and value of electrogustometry in otolaryngological research methods]. PMID- 6242652 TI - Attempts of inducing dimorphism in Trichophyton rubrum. PMID- 6242653 TI - [Reaction of the palatal tonsils after the application of a He-Ne laser]. PMID- 6242654 TI - [Effect on microbial growth of the He-Ne laser]. PMID- 6242655 TI - [Clinical aspects of skin spinaliomas in the area of the face and ears]. PMID- 6242656 TI - [Our experiences with Schobel's laterofixation]. PMID- 6242657 TI - [Functional and anatomical results of tympanoplasty using a fibrin glue]. PMID- 6242658 TI - The bone age in children with congenital heart disease. PMID- 6242659 TI - Lung and heart affection in rheumatoid arthritis. PMID- 6242661 TI - Aggressivity of children towards parents. PMID- 6242660 TI - Choriocarcinoma in pregnancy. Case report. PMID- 6242662 TI - [Female sexual reactivity and partner interaction]. PMID- 6242663 TI - [Educational problems of marriage and planned parenthood in the Czechoslovak SSR]. PMID- 6242664 TI - Contribution to the problem of professional decay of the teeth and periodontium. Part I--Methods. PMID- 6242665 TI - Contribution to the problem of professional decay of the teeth and periodontium. Part II--Results. PMID- 6242666 TI - [Morphometry of dental tissues]. PMID- 6242667 TI - Number of effective distractors of the school-achievement test item. PMID- 6242668 TI - Isolation, cultivation and identification of Cryptococcus neoformans from pigeons. PMID- 6242669 TI - Discrimination indices in the school-achievement test. Difference between average scores. PMID- 6242670 TI - Discrimination indices in the school-achievement test. Difference between score distributions. PMID- 6242671 TI - Problems of the skin resistance measuring in randomly chosen and so-called active points of the skin. PMID- 6242672 TI - The effect of piracetam on nonesterified fatty acids (NEFA) in rat brain during insulin hypoglycemia. PMID- 6242673 TI - The effect of nicotinamide on nonesterified fatty acids in the brain structures during painful stress. PMID- 6242674 TI - Effect of some drugs, experimental stress and estrus on unstable and fixed conditioned alimentary motor reflexes in cats. Part III. PMID- 6242675 TI - [Enzyme activity in the human embryonic and fetal intestinal wall]. PMID- 6242676 TI - CT scan and neuropsychological correlates of Alzheimer's disease and Huntington's disease. AB - "Cortical" and "subcortical" dementia syndromes differ in areas of primary neuropathology and clinical characteristics. Conventional CT scan interpretation, visual inspection of pictures, has not been useful in studying dementia. Recent studies of the digitally stored CT attenuation values have found systematic variations with normal aging and aphasia subtypes. In this study of numerical CT scan information in four Alzheimer's Disease and two Huntington's Disease patients, a double dissociation of frontal and temporal lobe density values was found, and a significant correlation was found between left temporal lobe density and verbal ability measures in the Alzheimer's Disease patients. PMID- 6242677 TI - [Glycopeptidases releasing intact N-linked oligosaccharides from glycopeptides]. PMID- 6242679 TI - The use of radioimmunoassays in obstetrics and gynecology. Proceedings of the 3rd symposium organized on the occasion of the 35th anniversary of the liberation of Czechoslovakia by the Soviet Army. Olomouc, May 1980. PMID- 6242678 TI - [Acquired immunodeficiency syndrome]. PMID- 6242680 TI - [Follow-up of the effect of prolactin-lowering substances]. PMID- 6242681 TI - Evaluation and treatment of hyperprolactinaemia in women of childbearing age. PMID- 6242682 TI - [Carbohydrate metabolism in normo- and hyperprolactinemic sterile patients and the possible treatment of sterility in juvenile diabetes mellitus with bromocriptine (Parlodel-Sandoz)]. PMID- 6242683 TI - Therapeutic effect of bromocriptine in anovulatory women with normal prolactin levels. PMID- 6242684 TI - [Changes in prolactin levels during anesthesia in gynecological operations]. PMID- 6242685 TI - [Insulin RIA for the determination of disorders of glucose metabolism in women taking steroid contraceptive preparations]. PMID- 6242686 TI - [The value of biochemical parameters in the prenatal diagnosis of intrauterine fetal retardation]. PMID- 6242687 TI - Gonadotropins in seminal plasma and blood serum and testosterone in blood serum of males treated for infertile marriage. PMID- 6242688 TI - [Steroid hormone receptor level in endometrial carcinoma]. PMID- 6242689 TI - Follow-up of prolactin levels in patients with breast cancer metastases treated by cryohypophysectomy. PMID- 6242690 TI - [Serum estetrol levels following i.v.administration of dehydroepiandrosterone sulfate in late pregnancy]. PMID- 6242691 TI - [RIA demonstration of primary prostaglandins in the decidua]. PMID- 6242692 TI - [Monitoring of at-risk pregnancies through E3 and HPL]. PMID- 6242693 TI - [Clinical value of radioimmunological HPL findings in the long-term care of threatened abortion]. PMID- 6242694 TI - [Clinical indications for the purposeful monitoring of at-risk pregnancies using radioimmunological HPL determinations]. PMID- 6242695 TI - [Radioimmunological assessment of the placental lactogen concentration in threatened abortion]. PMID- 6242696 TI - Dynamic follow-up of hCG in threatened premature labour. PMID- 6242697 TI - Preparation and evaluation of antisera to oxytocin. PMID- 6242698 TI - [The radioimmunological assay of progesterone in the diagnosis of corpus luteum insufficiency]. PMID- 6242699 TI - LH, FSH, estradiol and progesterone levels after discontinuation of hormonal contraception. PMID- 6242700 TI - Specificity of lymphocytotoxic antibodies in AIDS and pre-AIDS patients. AB - The number of T helper and T suppressor cells (determined with monoclonal antibodies) and the presence of serum lymphocytotoxic antibodies with T helper and T suppressor specificities were determined in 3 AIDS and 10 pre-AIDS patients and in 6 healthy homosexual and 17 healthy heterosexual controls. The 13 patients were 8 homosexuals and 5 drug addicts. Lymphocytotoxic antibodies were detected in all of the symptomatic individuals (AIDS and pre-AIDS) but in only 1 (6%) of the healthy heterosexual controls. Lymphocytotoxic antibodies in the patients ranged in titer from 125 to 625. The antibodies were detected at 15, 20, and 37 degrees C, but the reactivity at 37 degrees C was 20 to 40% lower than at 15 degrees C. All of the patients' antibodies reacted with both T helper and T suppressor cells, but in 9 sera the reaction was higher with the T helper and T (p less than 0.05). No correlation could be found between the patients' level of T helper lymphocytes or T helper/T suppressor cell ratios and their levels of lymphocytotoxic antibodies (p greater than 0.1). Sera of 7 patients and 3 of 9 healthy heterosexual controls reacted with non-T mononuclear cells (B cells plus monocytes). The degree of cytotoxicity with these cells did not correlate with the levels of lymphocytotoxic antibodies to T cells. PMID- 6242701 TI - Comparison of ADCC and NK activities of peripheral blood mononuclear cells from patients at risk for acquired immune deficiency syndrome (AIDS). AB - Numerous cellular immune defects have been described in patients with acquired immune deficiency syndrome (AIDS). These include anergy, reduced numbers of helper T cells, and decreased effectiveness of natural killer (NK) cells. In this study, we have measured the lytic activity of antibody-dependent cellular cytotoxic (K) cells using a recently described 51Cr release assay in patients clinically displaying lymphadenopathy syndrome (LAD). We then compared ADCC activity with NK activity, T helper/T suppressor ratios and NK cell number in these same patients. Our results indicate that a reduction of ADCC activity can occur in patients with LAD. In our study, patients that showed reduced ADCC activity also showed reduced NK cell function. Other individuals in this study had reduced NK function while ADCC values remained within the normal range. The degree of reversal of the T helper/T suppressor cell ratio was not a useful indicator of cellular immune function as measured by these assays in that individuals with very low ratios often had normal cytotoxic cell function while some patients with ratios in the normal range had decreased cytotoxicity. The percentage of NK cells as determined by HNK-1 monoclonal antibody also did not prove useful in defining potential cytotoxic activities. PMID- 6242702 TI - Transfusion induced acquired immunodeficiency syndrome (AIDS) with Kaposi's sarcoma in a patient with congenital factor V deficiency. AB - The first instance ever reported of transfusion induced AIDS with Kaposi's sarcoma in a non-homosexual patient is presented in detail. Our experience in this case supports the theory that a transfusion induced viral agent or agents which may affect the immunoregulatory mechanism could be the underlying cause. The rarity of patients such as ours suggests that other, so far undescribed, factors must be playing an essential role in the development of this rare form of cancer in high risk groups represented by patients with AIDS. Further studies are needed to ascertain the mechanisms whereby the different expressions of this syndrome are manifested in such patients. PMID- 6242703 TI - Cytogenetic diseases. PMID- 6242704 TI - The biochemical basis of gangliosidoses. PMID- 6242705 TI - The relationship of cimetidine to 5-hydroxytryptamine tissue levels in stress ulceration in the rat. AB - We studied the effect of cimetidine on 5-hydroxytryptamine (5-HT) levels in various tissues in restrained rats. Sixty male Sprague-Dawley rats, divided into four groups, received four intraperitoneal injections at 6-hour intervals in doses determined by body weight. Group I (control) was injected with saline (1 ml/300 gm) and was not restrained. Group II was injected with saline (1 ml/300 gm) and restrained for 18 hours beginning 1 hour after the first injection. Group III was injected with cimetidine (100 mg/kg) and was not restrained, whereas Group IV was injected with cimetidine (100 mg/kg) and restrained according to the schedule for Group II. The rats were killed and their stomachs were collected and graded for ulceration. 5-Hydroxytryptamine levels in the antrum and fundus of the stomach, the colon, the liver, and rectus abdominis muscle were determined by spectrophotofluorometry. Cimetidine prevented an increase in 5-HT in the antrum and protected against ulceration. As 5-HT levels in other tissues were not altered by restraint-induced stress, the phenomenon may be specific to the antrum. The protection against ulceration and elevated 5-HT levels conferred by cimetidine was comparable to that of vagotomy in similar models. PMID- 6242708 TI - [Prosthetic replacement of the suprarenal inferior vena cava: experimental model]. PMID- 6242706 TI - Inhibition of tumor cell metastasis by modulation of the vascular prostacyclin/thromboxane A2 system. AB - The interaction between metastasizing tumor cells and the hemostatic system of the host has been implicated in successful tumor cell dissemination. Prostacyclin (PGI2) decreases metastasis from tail vein injected B16 amelanotic melanoma (B16a) cells when administered 15 min prior to tumor cells. This effect is potentiated by a phosphodiesterase inhibitor. Initial trapping of 125I Udr labelled tumor cells in pulmonary vascular beds is unaltered by PGI2 but retention time is decreased. PGI2 decreases retention time even when administered 60 min post tumor cells. Structurally unrelated thromboxane (TX) synthetase inhibitors and a TXA2 receptor antagonist also reduce metastasis from tail vein injected B16a cells. Furthermore, one inhibitor, 1-(7-carboxyheptyl)imidazole, when injected intraperitoneally reduced spontaneous metastasis from subcutaneous B16a and Lewis lung carcinoma tumors. These results suggest that selective manipulation of PGI2 and TXA2 can reduce the hematogenous spread of tumor cells. PMID- 6242709 TI - [Flow selector valve for low pressure liquid chromatography]. PMID- 6242711 TI - Topically administered clindamycin in the treatment of acne vulgaris and other dermatologic disorders. AB - Clindamycin is a macrolide antibiotic that has been used orally and topically in the treatment of acne vulgaris. Unfortunately, oral administration is associated with pseudomembranous colitis in up to 10% of patients; consequently, it is no longer a generally accepted form of acne therapy. Topical application is an effective, safer alternative. Topical formulations may be extemporaneously prepared or purchased as a pre-mixed hydroalcoholic solution. Adverse effects associated with topical preparations are few and mostly minor. Topical clindamycin is also used in the treatment of erythrasma, rosacea, periorificial facial dermatitis, and folliculitis. PMID- 6242707 TI - Phenotypic drift and heterogeneity in response of metastatic mammary adenocarcinoma cell clones to adriamycin, 5-fluoro-2'-deoxyuridine and methotrexate treatment in vitro. AB - Rat 13762 mammary adenocarcinoma cell clones of differing spontaneous metastatic potentials were tested for their sensitivities to Adriamycin, 5-fluoro-2' deoxyuridine (FUdR) and methotrexate in vitro. Cells were treated 4 hours with a single dose of drug, and colony formation was used to assay cell survival. Dose response curves and survival parameters were calculated for local tumor-derived clones MTC and MTF7 and lung metastasis-derived clone MTLn3. The logarithmic curves were analyzed (slope and y-intercepts) for statistical comparisons. Heterogeneous sensitivities to Adriamycin and FUdR were observed, but there was no difference in the sensitivities of the clones to methotrexate cell killing. We could not find correlations between drug response and clonal origin, passage number or metastatic properties. The sensitivities of the clones to Adriamycin and FUdR changed upon in vitro passage, although drift in Adriamycin sensitivity during growth in culture was not statistically significant. The results demonstrate that clonal heterogeneity exists within the 13762 tumor and its metastases in their inherent responses to chemotherapy agents, and in the absence of host selective pressures tumor cells can spontaneously and reproducibly drift in their sensitivities to certain chemotherapeutic drugs. PMID- 6242712 TI - Studies in radiosensitizing effects of misonidazole and SR-2508 on C3H/He mouse mammary tumors. AB - The radiosensitizing efficacy of SR-2508, a new 2-nitroimidazole, which is less neurotoxic than misonidazole (MISO) was studied using transplantable mammary carcinoma of C3H/He mice. Tumor responses to treatments were evaluated by growth delay time assay. In single irradiations, the enhancement ratios of 0.5 mmole/kg of MISO and 1.5 mmole/kg of SR-2508, which were equitoxic to C3H/He mice, were 1.42 and 1.84 respectively. In fractionated irradiations with three fractions over two days or five fractions over four days, the enhancement ratios of 1.5 mmole/kg of SR-2508 were 1.40 and 1.34 respectively. On the other hand the enhancement ratios of MISO at the above mentioned dose in respective fractionated irradiations were 1.15 or 1.11. SR-2508 is considered promising as a hypoxic cell radiosensitizer for clinical use. PMID- 6242713 TI - [Facial paralysis occurring in chronic evolutive otitis]. PMID- 6242714 TI - [Viewpoints on the rehabilitation of deaf children]. PMID- 6242716 TI - [Etiopathogenic, clinical and therapeutic considerations in 2 cases of Melkersson Rosenthal syndrome]. PMID- 6242715 TI - [Scleroderma and its pathological manifestations in the ENT area]. PMID- 6242717 TI - [Maxillary paradental cyst appearing 26 years after radical maxilloethmoidal treatment]. PMID- 6242718 TI - [Reilly's neuroautonomic disorders of dentogenic origin]. PMID- 6242719 TI - [Results of treating ear suppurations with propolis]. PMID- 6242720 TI - [Complications of the combined treatment of malignant nasal and sinus tumors]. PMID- 6242721 TI - [Pathological tracheobronchial changes in esophageal neoplasms]. PMID- 6242722 TI - [Changes in the activity of oxidoreductases in tumors and peritumorous tissues. II]. PMID- 6242723 TI - [Serous otitis with a closed tympanum]. PMID- 6242724 TI - The amyloid deposits in Alzheimer's disease: their nature and pathogenesis. PMID- 6242725 TI - Experiences with the combined use of Mydocalm + Donalgin in the treatment of patients suffering from lumboischialgia. PMID- 6242726 TI - Disorders of glycogen metabolism of muscle. AB - This review will briefly outline the major steps of glycogen metabolism in muscle and the role of glycogen as a source of energy in different types of exercise. There are nine specific enzyme defects of glycogen metabolism or glycolysis affecting muscle. Each of the nine glycogenoses will be discussed in terms of typical and variant clinical presentation, genetic transmission, muscle biopsy and biochemical findings. The proposed pathophysiology of the various symptoms and signs will be presented and the many unsolved problems in this area will be discussed. PMID- 6242727 TI - [Prevention of caries of the first permanent molar using fissure sealants]. PMID- 6242728 TI - Chronic ruminative vomiting: a comparison of four treatment procedures. AB - An experimental analysis of a case of chronic ruminative vomiting in a 15-year old, profoundly retarded, Down's syndrome boy addressed the consequences of vomiting in the postmealtime environment. The experiment compared four treatments in each hour-long session using a multiple reinforcement schedule with order of the following procedures counterbalanced over days in a Latin square design: differential reinforcement of any behaviors other than vomiting (DRO) in which periods of no vomiting were followed by reinforcement and vomiting postponed reinforcement; differential reinforcement of specific behaviors alternative to vomiting (DRI) in which conjoint periods of no vomiting and sustained toy play were followed by reinforcement and the lack of either postponed reinforcement; extinction plus reinforcement of alternative behavior in which vomiting was ignored but toy play was reinforced; extinction in which vomiting was ignored. Data revealed an orderly dual cyclical pattern of vomiting throughout the day, with increased vomiting in the morning and immediately following food ingestion. Postluncheon treatments emphasizing reinforcement of alternative behavior were more successful in decreasing vomiting than DRO or extinction alone. PMID- 6242729 TI - Automatic category search and its transfer. AB - Experiments examined practice and transfer effects in consistently mapped (CM) and variably mapped (VM) semantic search. Experiment 1a examined improvements in reaction time in detecting words from a category as a function of the number of exemplars (4-12) in the category. All CM conditions showed improvement, but there was no significant effect of the number of exemplars. Experiment 1b examined the extent to which training on a subset of exemplars transferred to untrained members of the category. Results showed substantial positive transfer (60%-92%) to untrained exemplars from the trained category. The transfer was better if there were more exemplars in the training set. Experiment 2a showed practice reduced resource sensitivity in CM category search but did not benefit VM category search. Experiment 2b showed that under high workload, untrained exemplars of the trained CM category were detected when first presented to exhibit substantial positive transfer (70%). We conclude that many of the practice effects observed for CM category search take place at either the category level or the category feature level. We suggest that practice results in context activation of the category node or category features. This context activation hypothesis is evaluated with respect to major phenomena relating to automatic and controlled processing. PMID- 6242730 TI - Choice, similarity, and the context theory of classification. AB - Medin and Schaffer's (1978) context theory of classification learning is interpreted in terms of Luce's (1963) choice theory and in terms of theoretical results obtained in multidimensional scaling theory. En route to this interpretation, quantitative relationships that may exist between identification and classification performance are investigated. It is suggested that the same basic choice processes may operate in the two paradigms but that the similarity parameters that determine performance change systematically according to the structure of the choice paradigm. In particular, when subjects are able to attend selectively to the component dimensions that compose the stimuli, the similarity parameters may tend toward what is optimal for maximizing performance. PMID- 6242731 TI - Conceptual masking: the effects of subsequent visual events on memory for pictures. AB - Three experiments studied the effects of voluntary and involuntary focus of attention on recognition memory for pictures. Experiments 1 and 3 tested the conceptual-masking hypothesis, which holds that a visual event will automatically disrupt processing of a previously glimpsed picture if that event is new and meaningful. Memory for 112-ms pictures was tested under conditions where the to be-ignored 1.5-s interstimulus interval contained a blank field; a repeating picture; a new picture; a new, nonsense picture; or a new, inverted picture each time. The blank field, repeating picture, and new, nonsense picture did not disrupt memory as much as a new, meaningful picture, supporting the conceptual masking hypothesis. Experiment 2 studied voluntary attentional control of encoding by instructing subjects to focus attention on the brief pictures, all pictures, or the long pictures in a sequence. Recognition memory for pictures of both durations showed a striking ability of observers to process pictures selectively. The possible role of these effects in visual scanning are discussed. PMID- 6242732 TI - Intact retention in acute alcohol amnesia. AB - Research on alcohol amnesia has focused on memory processes that are disrupted during intoxication. The present experiment examined the possibility that certain memory processes might be resistant to the amnesic effects of alcohol. Intoxicated and sober subjects studied a list of 29 words. They were then given one of three different retention tests: free recall, identification of degraded words based on the procedure used by Warrington and Weiskrantz (1970), and yes/no recognition. As expected, free recall was significantly impaired by alcohol intoxication. In contrast, in the identification test, intoxicated subjects benefited to the same degree as sober subjects from prior exposure to the items. The two groups did not differ in immediate recognition memory. The results of the free-recall and identification tasks are similar to findings with chronic amnesic patients and suggest that perceptual fluency is not affected by alcohol, whereas elaborative processes supporting recall are particularly sensitive to disruption during intoxication. The failure to find recognition impairment at the level of intoxication used in this study distinguishes temporary alcohol amnesia from chronic amnesia. PMID- 6242733 TI - A retrieval account of the long-term modality effect. AB - When to-be-remembered (TBR) word pairs are separated by distractor activity, recall of the last few audibly presented pairs is greater than recall of the last few visually presented pairs. The effect is found even after a considerably long distractor-filled retention interval. Five experiments disconfirm echoic storage, short-term storage and long-term storage accounts of these effects, as well as demonstrating that the effect is not an artifact of differential use of a recency first output strategy. The data are generally consistent with the proposition that retrieval is disrupted by modality-specific similarity between to-be remembered items and distractor information. PMID- 6242734 TI - The information that amnesic patients do not forget. AB - The performance of three kinds of amnesic patients and control subjects was assessed using four methods for testing memory: free recall, recognition, cued recall, and word completion. Whereas amnesic patients were impaired on free recall, recognition, and cued recall, they were normal on word completion. Moreover, performance on the word-completion test declined at a normal rate reaching chance after about 120 min. The word-completion test resembled the cued recall test in that the initial letters of previously presented words were given as cues. It differed from cued recall only in the instructions, which directed subjects away from the memory aspects of the test and asked them to complete each three-letter cue with the first word that came to mind. The present results offer an explanation of conflicting findings that have been obtained with amnesic patients on tests of the cued-recall type. The results are considered in terms of a process (activation or procedural learning), which is spared in amnesia and not dependent on the integrity of the damaged brain regions. PMID- 6242735 TI - Cognitive arithmetic: comparison of operations. AB - Adults' performance of simple arithmetic calculations (addition, multiplication, and numerical comparison) was examined to test predictions of digital (counting), analog, and network models. Although all of these models have been supported by studies of mental addition, each leads to a different prediction concerning relations between the times required for addition, multiplication, and numerical comparison. Pairs of single-digit integers were presented and reaction times (RTs) for adding, multiplying, and comparing the stimuli were collected. A high correlation between RT for addition and multiplication of the same digits was obtained. This result is consistent with a network model, but presents difficulties for both analog and counting models. A "ties" effect of no increase in RT with increases in problem size for doubles such as 2 + 2 has been found in previous studies of addition using verification procedures, but was not found with the production task employed in the present study. Instead, a different kind of ties effect was found. Reaction time for both addition and multiplication of ties increased more slowly with problem size than did RT for non-tie problems. This ties effect, and the finding that probability of making errors contributes independently of problem size to RT support a distinction between location and accessibility of information in a network. PMID- 6242736 TI - Representation of linear orders. AB - Two binary classification tasks were used to explore the associative structure of linear orders. In Experiment 1, college students classified English letters as targets or nontargets, the targets being consecutive letters of the alphabet. The time to reject nontargets was a decreasing function of the distance from the target set, suggesting response interference mediated by automatic associations from the target to the nontarget letters. The way in which this interference effect depended on the placement of the boundaries between the target and nontarget sets revealed the relative strengths of individual interletter associations. In Experiment 2, students were assigned novel linear orders composed of letterlike symbols and asked to classify pairs of symbols as being adjacent or nonadjacent in the assigned sequence. Reaction time was found to be a joint function of the distance between any pair of symbols and the relative positions of those symbols within the sequence. The effects of both distance and position decreased systematically over 6 days of practice with a particular order, beginning at a level typical of unfamiliar orders and converging on a level characteristic of familiar orders such as letters and digits. These results provide an empirical unification of two previously disparate sets of findings in the literature on linear orders, those concerning familiar and unfamiliar orders, and the systematic transition between the two patterns of results suggests the gradual integration of a new associative structure. PMID- 6242737 TI - Processing category terms in context: instantiation and the structure of semantic categories. AB - The present study sought to determine if semantic categories processed in context are encoded as particular exemplars. In Experiment 1 we replicated previous results on an extended and modified set of stimuli by showing that when subjects read sentences containing a category term in a context designed to bias encoding toward an atypical exemplar, the atypical exemplar serves as a better retrieval cue than a typical exemplar. In Experiment 2 we tested whether these cued-recall results were due to processes operating at encoding or retrieval. The pattern of semantic interference obtained in a modified Stroop paradigm clearly contradicted the position that readers routinely encode general terms as examples, or "instantiations." In particular, there was significant color-naming interference when typical exemplars served as targets even when preceded by sentences designed to bias encoding toward an atypical exemplar. No significant color-naming interference was generated to atypical exemplars. Experiment 3 ruled out the possibility that differences between the cued-recall and Stroop results in the first two experiments were due to encoding strategy differences. It was concluded that assigning a referent to a category term is not a routine activity in sentence encoding and that processing category terms entails activation of summary representations. PMID- 6242738 TI - Memory as a function of attention, level of processing, and automatization. AB - The relationships between long-term memory (LTM) modification, attentional allocation, and type of processing are examined. Automatic/controlled processing theory (Schneider & Shiffrin, 1977) predicts that the nature and amount of controlled processing determines LTM storage and that stimuli can be automatically processed with no lasting LTM effect. Subjects performed the following: (a) an intentional learning, (b) a semantic categorization, (c) a graphic categorization, (d) a distracting digit-search while intentionally learning words, and (e) a distracting digit-search while ignoring words. Frequency judgments were more accurate in the semantic and intentional conditions than the graphic condition. Frequency judgments in the digit-search conditions were near chance. Experiment 2 extensively trained subjects to develop automatic categorization. Automatic categorization produced no frequency learning and little recognition. These results also disconfirm the Hasher and Zacks (1979) "automatic encoding" proposal regarding the nature of processing. PMID- 6242739 TI - Representation of serial order in speech: evidence from the repeated phoneme effect in speech errors. AB - Previous research has shown that slips of the tongue involving the exchange of phonemes (e.g., left hemisphere----left hemisphere) are often characterized by a repeated phoneme next to the exchanging ones (the vowel /epsilon/ in the above example is next to both of the exchanging sounds, /l/ and /h/). Two experiments, which elicited slips of the tongue under controlled conditions, revealed that repeated sounds in a speech plan are contributory causes of phoneme exchanges, anticipations, and perseverations. In addition, it was found that repeated sounds induce the misordering of sounds that are not adjacent to the repeated ones, as well as those that are adjacent to the repeated ones. An analysis of a collection of natural slips also supported the conclusion that repeated sounds cause nonadjacent sounds to slip. The results are seen as inconsistent with serial order theories that propose a linear structure of sounds held together by contextual influences between adjacent phonemes. PMID- 6242741 TI - Global and local control of choice behavior by cyclically varying outcome probabilities. AB - Subjects asked to simulate decision makers in a competitive bidding situation chose repeatedly between two alternatives; reward probability varied according to a sine wave function of time for one alternative but was held constant over time for the other. Learning functions for choice probability exhibited the wavelike pattern predicted by a statistical learning model. However, on later transfer trials, when success probability was independent of subjects' choices, their choice behavior continued to follow a wavelike function rather than approaching the constant .5 level predicted by the learning model. A possible basis in memory for the transfer performance was revealed in subjects' sketches of the remembered pattern of variation in reward probabilities. It is concluded that choice performance is controlled by a mixture of local feedback, in a manner described by the learning model, and more global information encoded in an abstract memory representation, with the balance of the influence shifting toward the latter when local feedback becomes uninformative. PMID- 6242740 TI - Induction of category distributions: a framework for classification learning. AB - We present a framework for classification learning that assumes that learners use presented instances (whether labeled or unlabeled) to infer the density functions of category exemplars over a feature space and that subsequent classification decisions employ a relative likelihood decision rule based on these inferred density functions. A specific model based on this general framework, the category density model, was proposed to account for the induction of normally distributed categories either with or without error correction or provision of labeled instances. The model was implemented as a computer simulation. Results of five experiments indicated that people could learn category distributions not only without error correction, but without knowledge of the number of categories or even that there were categories to be learned. These and other findings dictated a more general learning model that integrated distributional representations based on both parametric descriptions and stored instances. PMID- 6242742 TI - Odor recognition: familiarity, identifiability, and encoding consistency. AB - The investigation examined the association between the perceived identity of odorous stimuli and the ability to recognize the previous occurrence of them. The stimuli comprised 20 relatively familiar odorous objects such as chocolate, leather, popcorn, and soy sauce. Participants rated the familiarity of the odors and sought to identify them. At various intervals up to 7 days after initial inspection, the participants sought to recognize the odors among sets of distractor odors that included such items as soap, cloves, pipe tobacco, and so on. The recognition response entailed a confidence rating as to whether or not an item had appeared in the original set. At the time of testing, the participants also sought to identify the stimuli again. The results upheld previous findings of excellent initial recognition memory for environmentally relevant odors and slow forgetting. The results also uncovered, for the first time, a strong association between recognition memory and identifiability, rated familiarity, and the ability to use an odor label consistently at inspection and subsequent testing. Encodability seems to enhance rather than to permit recognizability. Even items identified incorrectly or inconsistently were recognized at levels above chance. PMID- 6242743 TI - Talk is getting cheap. PMID- 6242744 TI - Radiography of persons with developmental disabilities. AB - This article is a proposal to provide guidelines for the radiographer confronted with the patient who is mentally retarded or developmentally disabled. Criteria for an informal evaluation are identified, as well as special methods of positioning and immobilization. PMID- 6242745 TI - The higher nervous activity. XXVIII. Parietal lobes of human cerebral hemispheres. PMID- 6242746 TI - Toenail disorders. AB - The nail unit provides clues to neoplasms and systemic disease. It also may be prominent as a site for fungal and bacterial infections. Primary dermatologic disorders present a broad spectrum of nail changes. The complete physician, regardless of his field, needs to be alert to the often significant manifestations of the abnormal nail as a signal to important pathology. PMID- 6242747 TI - Occupational dermatoses. PMID- 6242749 TI - Objects, parts, and categories. AB - Concepts may be organized into taxonomies varying in inclusiveness or abstraction, such as furniture, table, card table or animal, bird, robin. For taxonomies of common objects and organisms, the basic level, the level of table and bird, has been determined to be most informative (Rosch, Mervis, Gray, Johnson, & Boyes-Braem, 1976). Psychology, linguistics, and anthropology have produced a variety of measures of perception, behavior, and communication that converge on the basic level. Here, we present data showing that the basic level differs qualitatively from other levels in taxonomies of objects and of living things and present an explanation for why so many measures converge at that level. We have found that part terms proliferate in subjects' listings of attributes characterizing category members at the basic level, but are rarely listed at a general level. At a more specific level, fewer parts are listed, though more are judged to be true. Basic level objects are distinguished from one another by parts, but members of subordinate categories share parts and differ from one another on other attributes. Informants agree on the parts of objects, and also on relative "goodness" of the various parts. Perceptual salience and functional significance both appear to contribute to perceived part goodness. Names of parts frequently enjoy a duality not evident in names of other attributes; they refer at once to a particular appearance and to a particular function. We propose that part configuration underlies the various empirical operations of perception, behavior, and communication that converge at the basic level. Part configuration underlies the perceptual measures because it determines the shapes of objects to a large degree. Parts underlie the behavioral tasks because most of our behaviors is indirect toward parts of objects. Labeling appears to follow the natural breaks of perception and behavior; consequently, part configuration also underlies communication measures. Because elements of more abstract taxonomies, such as scenes and events, can also be decomposed into parts, this analysis provides a bridge to organization in other domains of knowledge. Knowledge organization by parts (partonomy) is contrasted to organization by kinds (taxonomy). Taxonomies serve to organize numerous classes of entities and to allow inference from larger sets to sets included in them. Partonomies serve to separate entities into their structural components and to organize knowledge of function by components of structure. The informativeness of the basic level may originate from the availability of inference from structure to function at that level. PMID- 6242748 TI - Comparison of the nature and frequency of medical problems among patients in general, specialty and hospital dental practices. PMID- 6242750 TI - Three gradients and the perception of flat and curved surfaces. AB - Researchers of visual perception have long been interested in the perceived slant of a surface and in the gradients that purportedly specify it. Slant is the angle between the line of sight and the tangent to the planar surface at any point, also called the surface normal. Gradients are the sources of information that grade, or change, with visual angle as one looks from one's feet upward to the horizon. The present article explores three gradients--perspective, compression, and density--and the phenomenal impression of flat and curved surfaces. The perspective gradient is measured at right angles to the axis of tilt at any point in the optic array; that is, when looking down a hallway at the tiles of a floor receding in the distance, perspective is measured by the x-axis width of each tile projected on the image plane orthogonal to the line of sight. The compression gradient is the ratio of y/x axis measures on the projected plane. The density gradient is measured by the number of tiles per unit solid visual angle. For flat surfaces and many others, perspective and compression gradients decrease with distance, and the density gradient increases. We discuss the manner in which these gradients change for various types of surfaces. Each gradient is founded on a different assumption about textures on the surfaces around us. In Experiment 1, viewers assessed the three-dimensional character of projections of flat and curved surfaces receding in the distance. They made pairwise judgments of preference and of dissimilarity among eight stimuli in each of four sets. The presence of each gradient was manipulated orthogonally such that each stimulus had zero, one, two, or three gradients appropriate for either a flat surface or a curved surface. Judgments were made were made for surfaces with both regularly shaped and irregularly shaped textures scattered on them. All viewer assessment were then scaled in one dimension. Multiple correlation and regression on the scale values revealed that greater than 98% of the variance in scale values was accounted for by the gradients. For the flat surfaces a mean of 65% of the variance was accounted for by the perspective gradient, 28% by the density gradient, and 6% by the compression gradient. For curved surfaces, on the other hand, a mean of 96% of the variance was accounted for by the compression gradient, and less than 2% by either the perspective gradient or the density gradient.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 6242751 TI - On gradients and texture "gradients". AB - Texture gradients, systematic variations in image texture due to perspective projection of surface texture, provide information about the shape and disposition of surfaces relative to a viewer. Although this three-dimensional information is usually described in terms of mathematical relationships involving gradients of image properties (Cutting & Millard, 1984), the perceptual processes that derive this information need not necessarily measure or register these gradients explicitly (Stevens, 1981). It is difficult to conclude, therefore, that the perception of, say, flatness or curvature derives from processes that capitalize on these gradient relationships, per se. The difficulty becomes most apparent when attempting to formalize the perceptual computations and the spatial information that is made explicit. PMID- 6242752 TI - Awareness of the response after feedback training for changes in heart rate and sudomotor laterality. AB - What is the relation between the ability to control visceral responding on a biofeedback task and the ability to report behaviors actually contributing to this performance? Subjects received biofeedback training for unidentified visceral responses and then gave written reports about what they had done to control the feedback displays. Independent judges were given these reports and, on the basis of knowledge about activities known to contribute to visceral activity, were asked to determine the visceral responses for which the subjects had been trained. The reports of subjects who succeeded at bidirectional control of heart rate (Experiment 1) or sudomotor laterality (Experiment 2) showed awareness of behaviors related to feedback as assessed by this procedure, whereas the reports of subjects who failed at bidirectional control did not. Subsequent experiments indicated that these results did not depend on a learning strategy that might have been specific to the initial studies. These findings call into question the view that people are unaware of what they have done to produce the response after training on biofeedback tasks. Earlier studies reporting lack of awareness in biofeedback are discussed in light of factors that affect the measurement of biofeedback learning and response awareness. PMID- 6242753 TI - Resolving 20 years of inconsistent interactions between lexical familiarity and orthography, concreteness, and polysemy. AB - Numerous word recognition studies conducted over the past 2 decades are examined. These studies manipulated lexical familiarity by presenting words of high versus low printed frequency and most reported an interaction between printed frequency and one of several second variables, namely, orthographic regularity, semantic concreteness, or polysemy. However, the direction of these interactions was inconsistent from study to study. Six new experiments clarify these discordant results. The first two demonstrate that words of the same low printed frequency are not always equally familiar to subjects. Instead, subjects' ratings of "experimental familiarity" suggest that many of the low-printed-frequency words used in prior studies varied along this dimension. Four lexical decision experiments reexamine the prior findings by orthogonally manipulating lexical familiarity, as assessed by experiential familiarity ratings, with bigram frequency, semantic concreteness, and number of meanings. The results suggest that of these variables, only experiential familiarity reliably affects word recognition latencies. This in turn suggests that previous inconsistent findings are due to confounding experiential familiarity with a second variable. PMID- 6242754 TI - Accuracy of feeling-of-knowing judgments for predicting perceptual identification and relearning. AB - The feeding of knowing refers to predictions about subsequent memory performance on previously nonrecalled items. The most frequently investigated type of subsequent performance has been recognition. The present research explored predictive accuracy with two new feeling-of-knowing criterion tests (in addition to recognition): relearning and perceptual identification. In two experiments, people attempted to recall the answers to general-information questions such as, "What is the capital of Australia?", then made feeling-of-knowing predictions for all nonrecalled answers, and finally had a criterion test to assess the accuracy of the feeling-of-knowing predictions. Experiment 1 demonstrated that perceptual identification can be employed successfully as a criterion test for the feeling of knowing. This opens a new way for metamemory research via perception. Moreover, the feeling-of-knowing accuracy for predicting perceptual identification was not significantly correlated with the feeling-of-knowing accuracy for predicting recognition, in accord with the idea that these two tests assess memory differently. Experiment 2 demonstrated that relearning performance can also be predicted by feeling-of-knowing judgments. Both experiments showed that there is a positive relationship between the feeling of knowing and the amount of time elapsing before a memory search is terminated during recall. Further analyses showed that this relationship is substantial for nonrecalled items for which the person did not guess an answer (omission errors), but the relationship is null or negative for nonrecalled items that the person guessed incorrectly (commission errors). Several theoretical mechanisms that may underlie the feeling of knowing are proposed. PMID- 6242756 TI - Selective inhibition of adenovirus type 2 early region II and III transcription by an anisomycin block of protein synthesis. AB - The transcription of adenovirus type 2 genes proceeds through a broad three-phase program. From 1 to 4 h postinfection six early transcription units (EIa, EIb, EII, EIII, EIV, and the promoter-proximal segment of the late transcription unit) are activated. From 4 to 6 h postinfection transcription of the early genes is depressed. After the onset of viral DNA replication at approximately 6 h postinfection, the transcript from the late promoter is antiterminated, and this transcript dominates viral RNA synthesis. The early activation period also proceeds through a series of stages; early regions EIa and EIV are activated first, followed by early region EII. We show that in the presence of anisomycin, a stringent inhibitor of protein synthesis, nuclear RNA and cytoplasmic polyadenylated RNA from regions EIa and EIV accumulate at normal rates, whereas RNAs from regions EII and EIII do not accumulate. We also show that failure to accumulate RNAs from regions EII and EIII is due to reduction of the rate of transcription by greater than 90%. We conclude that the regulation of the promoters for early regions EII and EIII is distinct from the mechanism that operates on the other early transcription units. The promoters for early regions EII and EIII diverge and lie approximately 500 nucleotides apart. We examined the structure of viral chromatin in this region early during infection by mild DNase I digestion in isolated nuclei and indirect end labeling with a DNA probe near these promoters. In control, drug-free cells where EII and EIII are transcribed and in anisomycin-treated cells where EII and EIII are not transcribed we detect the same regular DNase I pattern. We suggest that regulation of EII and EIII is not mediated through a change in gross chromatin structure, but rather by a viral effector, possibly a product of region EIa. PMID- 6242755 TI - Genetics of the mammalian oxidative phosphorylation system: characterization of a new oligomycin-resistant Chinese hamster ovary cell line. AB - The properties of a new type of oligomycin-resistant Chinese hamster ovary (CHO) cell line (Olir 2.2) are described in this paper. Olir 2.2 cells were approximately 50,000-fold more resistant to oligomycin than were wild-type CHO cells when tested in glucose-containing medium, but only 10- to 100-fold more resistant when tested in galactose-containing medium. Olir 2.2 cells grew with a doubling time similar to that of wild-type cells both in the presence or absence of oligomycin. Oligomycin resistance in Olir 2.2 cells was stable in the absence of drug. In vitro assays indicated that there was approximately a 25-fold increase in the resistance of the mitochondrial ATPase to inhibition by oligomycin in Olir 2.2 cells, with little change in the total ATPase activity. The electron transport chain was shown to be functional in Olir 2.2 cells. Olir 2.2 cells were cross-resistant to other inhibitors of the mitochondrial ATPase (such as rutamycin, ossamycin, peliomycin, venturicidin, leucinostatin, and efrapeptin) and to other inhibitors of mitochondrial functions (such as chloramphenicol, rotenone, and antimycin). Oligomycin resistance was expressed codominantly in hybrids between Olir 2.2 cells and wild-type cells. Cross resistance to ossamycin, peliomycin, chloramphenicol, antimycin, venturicidin, leucinostatin, and efrapeptin was also expressed codominantly in hybrids. Fusions of enucleated Olir 2.2 cells with wild-type cells and characterization of the resulting cybrid clones indicated that resistance to oligomycin and ossamycin results from a mutation in both a nuclear gene and a cytoplasmic gene. Cross resistance to efrapeptin, leucinostatin, venturicidin, and antimycin results from a mutation in only a nuclear gene. PMID- 6242757 TI - Detection of three-dimensional structure in moving optical patterns. AB - Three experiments examined parameters affecting human observers' ability to detect the global three-dimensional (3D) organization of a random-dot display corresponding to the polar projection of a rotating sphere. Results indicate that the detection of 3D structure is critically dependent on the detectability of motion, is disrupted by increased redundant information specifying the two dimensional location of points in the display, and undergoes a rapidly increasing resistance to the disruptive effects of noise with increasing numbers of frames. These results, in conjunction with earlier findings, are inconsistent with existing theories concerning the perception of three-dimensionality in moving displays, in that they indicate a high degree of visual sensitivity to stimulus organizations with unique topological representations. PMID- 6242758 TI - Does rate of processing determine ease of target detection? AB - In a complex target identification task, Krumhansl (1982) reported that ease of target detection was inversely related to the exposure duration of contextual elements in the display. This relationship held at brief exposures of the contextual elements. However, in Krumhansl's design, brightness and duration covaried. Hence, the results cannot be ascribed unambiguously to the effect of duration alone. In the present two experiments, brightness and duration were varied independently. The outcome showed that brightness differences were both a necessary and a sufficient condition for producing the relationships observed by Krumhansl. In fact, when brightness was equalized across all durations the relationship was reversed. Although unable to account for the effects of duration, Krumhansl's formal model remains viable as a predictor of the effects of brightness. PMID- 6242759 TI - Emergent features, attention, and object perception. AB - The perceptual processing of arrows and triangles and of their component angles and lines was explored in a number of different tasks. The results suggest that some analysis of shapes into simpler parts occurs preattentively, because these parts can recombine to form illusory conjunctions when attention is divided. The presence of "emergent features," such as closure or arrow junctions, was inferred from predicted correlations in the pattern of performance across tasks and across individual subjects. Thus triangles (for most subjects) and arrows (for some subjects) behave as if they had a perceptual feature that is absent from their parts and that mediates parallel detection in search and easy texture segregation. For some subjects, circles could apparently supply the additional feature (presumably closure) required to form illusory triangles from their component lines, whereas for other subjects circles had no effect. The fact that triangle lines can form illusory conjunctions with another shape makes it unlikely that triangles are perceived holistically and strengthens the interpretation that relies on emergent features. PMID- 6242760 TI - The pretreatment weighting technique. AB - A common procedure that is frequently used in perceptual studies interested in group differences (e.g., young vs. aged) involves initially equating all subjects in a pretreatment condition by differentially weighting the subjects on a particular stimulus dimension. The experimental treatment of interest is then introduced to these equal-baseline groups. The present article questions the general validity of this procedure by focusing on the critical assumption that the pretreatment weighting and the experimental treatment are independent. A research example is included demonstrating that differentially weighting individuals in order to produce equal-baseline performance may, in fact, provide the basis for later performance differences under the experimental treatment. PMID- 6242761 TI - On the relationship between stimulus intensity and duration of visible persistence. AB - Stimulus intensity and duration of visible persistence have been found to vary directly in some studies but inversely in others. Hawkins and Shulman (1979) have proposed that this inconsistency can be resolved by separating the studies that employed a decrement-threshold measure of persistence (Type I measure) from those that measured the total duration of persistence (Type II measure). They suggested that Type I measures yield an inverse relationship, whereas Type II measures yield a direct relationship between intensity and persistence. Hawkins and Shulman's model is incomplete in ways that are easily remedied. However, the model is totally contradicted by the experimental evidence. A new resolution of the inconsistent results is proposed in terms of retinal afterimages. PMID- 6242762 TI - Searching for conjunctively defined targets. AB - It has recently been proposed that in searching for a target defined as a conjunction of two or more separable features, attention must be paid serially to each stimulus in a display. Support for this comes from studies in which subjects searched for a target that shared a single feature with each of two different kinds of distractor items (e.g., a red O in a field of black Os and red Ns). Reaction time increased linearly with display size. We argue that this design may obscure evidence of selectivity in search. In an experiment in which the numbers of the two distractors were unconfounded, we find evidence that subjects can search through specified subsets of stimuli. For example, subjects told to search through just the Os to find the red O target do so without searching through Ns. Implications of selective search are discussed. PMID- 6242763 TI - Attention in the processing of complex visual displays: detecting features and their combinations. AB - The distinction between operations in visual processing that are parallel and preattentive and those that are serial and attentional receives both theoretical and empirical support. According to Treisman's feature-integration theory, independent features are available preattentively, but attention is required to veridically combine features into objects. Certain evidence supporting this theory is consistent with a different interpretation, which was tested in four experiments. The first experiment compared the detection of features and feature combinations while eliminating a factor that confounded earlier comparisons. The resulting priority of access to combinatorial information suggests that features and nonlocal combinations of features are not connected solely by a bottom-up hierarchical convergence. Causes of the disparity between the results of Experiment 1 and the results of previous research were investigated in three subsequent experiments. The results showed that of the two confounded factors, it was the difference in the mapping of alternatives onto responses, not the differing attentional demands of features and objects, that underlaid the results of the previous research. The present results are thus counterexamples to the feature-integration theory. Aspects of this theory are shown to be subsumed by more general principles, which are discussed in terms of attentional processes in the detection of features, objects, and stimulus alternatives. PMID- 6242764 TI - Automatic and expectancy-based priming effects in a digit naming task. AB - In a voice reaction time task, subjects named target digits that were horizontally flanked by noise digits or by a neutral symbol (#). For the control subjects, the noise digits were uncorrelated with the target digit, whereas for three experimental groups, the value of the noise digit predicted the target digit by an arithmetic rule (target = noise, target = noise + 1, target = noise - 1) on 75% of the trials. Patterns of reaction time facilitation and inhibition relative to the control condition among the four subject groups illustrated differing time courses of involuntary and expectancy-based priming. For prediction rules requiring an arithmetic transformation (expect N = 1 and expect N - 1), responses to predicted targets were slowed by response competition at short stimulus-onset asynchrony (SOAs) but greatly facilitated by expectancy at longer SOAs. PMID- 6242765 TI - Time course of visual information utilization during fixations in reading. AB - College students read short texts from a cathode-ray tube as their eye movements were being monitored. During selected fixations, the text was briefly masked and then it reappeared with one word changed. Subjects often were unaware that the word had changed. Sometimes they reported seeing the first presented word, sometimes the second presented word, and sometimes both. When only one word was reported, two factors were found to determine which one it was: the length of time a word was present during the fixation and the predictability of a word in its context. The results suggested that visual information is utilized for reading at a crucial period during the fixation and that this crucial period can occur at different times on different fixations. The pattern of responses suggested that the first letter of a word is not utilized before other letters and that letters are not scanned from left to right during a fixation. PMID- 6242766 TI - Effects of perceptual quality on the processing of human faces presented to the left and right cerebral hemispheres. AB - Three experiments examined the effects of stimulus duration, retinal eccentricity, and visual noise on the processing of human faces presented to the left visual field/right hemisphere (LVF-RH) and right visual field/left hemisphere (RVF-LH). In Experiment 1 observers identified which of 10 similar male faces was presented on a screen. The single face was presented for 10, 55, or 100 ms at 1 degree, 4 degrees, or 9 degrees of visual angle to the left or right of fixation. Decreasing stimulus duration and increasing retinal eccentricity lowered face recognition. The effect of duration was the same for LVF-RH and RVF-LH trials, but the detrimental effect of increasing retinal eccentricity was larger on LVF-RH trials than on RVF-LH trials. In Experiment 2 observers indicated whether a single face from this same set was a member of a memorized set of five positive faces. The probe face on each trial was presented alone or embedded in visual noise. Visual noise increased the error rate more on LVF-RH trials than on RVF-LH trials. This effect was replicated in Experiment 3, which also required observers to make a much easier discrimination between male and female faces. In the male/female task visual noise tended to impair performance more on RVF-LH trials than on LVF-RH trials, opposite the effect for the male/male task. These results are discussed in terms of hemispheric asymmetry for global versus local features of faces, the level of feature analysis demanded by a task, and the level of feature analysis most disrupted by perceptual degradation. PMID- 6242767 TI - [Non-phosphorylative transglycosylation in extracts from white and red muscles of carp (Cyprinus carpio L.)]. AB - The enzymatic, nonphosphorylative reaction of transglycosylation in extracts from white and red muscles of the carp was studied. Amylomaltase (EC 2.4.1.25) activity was assayed using p-nitrophenyl-N-maltoside as substrate and the amount of p-nitrophenyl-N-maltotrioside was assumed as a measure of the enzyme activity. The pH and temperature optimum of the reaction was examined. In both types of muscles significant differences in transglycosylative activity and its decrease immediately after prolonged transport of carps were found. PMID- 6242768 TI - The immunological approach to the enigma of sarcoidosis. PMID- 6242769 TI - Respiratory disability in workers' compensation claimants. AB - This study was designed to examine whether claimants for compensation for work related respiratory impairment due to chronic airflow obstruction exhibited greater symptoms of disablement than other patients with similar obstruction. It also sought evidence of bias, either towards or against the claimants, by the medical examiners. One hundred and twenty-eight subjects (68 claimants) with chronic asthma, chronic bronchitis, and emphysema were studied. There was a reasonable concordance of subjective judgements between patients and medical examiners in 81% of the disabled workers, and in 90% of the other medical group. Similarly, impairment of lung function (FEV1/VC ratio) in both groups was comparable at most levels of subjective disability. It was concluded that, in contrast to some previous reports, claimants for compensation for work-related chronic obstructive airway diseases did not tend to exaggerate their disabilities. This does not imply that the claimants' ailments were necessarily occupation-related. PMID- 6242770 TI - Guidelines on contraception. AFFPA Medical Task Force. The Australian Federation of Family Planning Associations. PMID- 6242771 TI - Microalbuminuria predicts mortality in non-insulin-dependent diabetics. AB - Forty-four non-insulin-dependent diabetics (NIDD), all with urine negative to Albustix, were studied in 1966/67. By the end of 1980, 17 had died, all but two from cardiovascular causes. All causes of mortality and time to death were significantly related in univariate analyses to age and to the overnight urinary albumin excretion rate (AER), but not to systolic and diastolic blood pressure levels or to duration of diabetes when the latter was corrected for age. Age and duration were highly correlated with each other. In multivariate analyses age and AER were independent predictors of both mortality and time to death, with AER having the greater degree of significance. Thus subclinically elevated albumin excretion rates ('microalbuminuria') indicate a substantially increased mortality risk in non-insulin-dependent diabetes. PMID- 6242772 TI - Continuous subcutaneous insulin infusion as a treatment option: a perspective after seven years of research applications. PMID- 6242773 TI - Technological aspects of CSII. PMID- 6242774 TI - Starting pump therapy. PMID- 6242775 TI - Problems and safety of continuous subcutaneous insulin infusion. PMID- 6242776 TI - Pump therapy in children. PMID- 6242777 TI - Continuous subcutaneous insulin infusion (CSII): therapeutic options. PMID- 6242778 TI - Need stable diabetics mix their insulins? AB - Ten insulin-dependent diabetics taking twice-daily mixtures of soluble and isophane insulin were studied in a double-blind crossover trial to examine the effect on their glycaemic control of a fixed-mixture preparation (containing either 50% soluble, 50% isophane or 30% soluble, 70% isophane) given in the same total dose as each patient's usual mixture. The mean (+/- S.E.M.) of eight daily blood glucose determinations when the patients' usual mixtures were pre-mixed by the hospital pharmacy was 7.6 +/- 0.7 mmol/l, 7.8 +/- 0.8 mmol/l when the fixed mixture preparation was used and 8.0 +/- 0.5 mmol/l when the patients drew up and mixed the insulins themselves. Individual glucose profiles on each of the three regimens expressed as mean modified log 'M' indices were 1.26 +/- 0.14, 1.29 +/- 0.16 and 1.37 +/- 0.14, respectively. Thus, the patients studied were as well controlled on a fixed-mixture preparation as on their usual 'tailormade' insulin regimens. PMID- 6242779 TI - Growth hormone response to hyperinsulinaemia in insulin-dependent diabetics. Comparison of patients with and without retinopathy. AB - Growth hormone levels were measured in glucose clamp studies on 13 insulin dependent diabetic patients with retinopathy and 9 age, sex, and weight matched patients without retinopathy. Four non-diabetic subjects were used as controls. The glucose was kept constant at 12 +/- 0.85 mmol/l (mean +/- S.D.) in the diabetic groups, and at 6 mmol/l in the non-diabetic controls. Insulin was infused at sequential rates of 0.3, 1.0, and 10 mU/kg/min. Basal levels of growth hormone were not significantly different in those with and without retinopathy (5.7 +/- 4.9, 9.4 +/- 10.6 mU/l p = 0.21). Growth hormone levels were compared in each group during a 60 minute steady state period for each insulin infusion rate. At all 3 infusion rates, the diabetics with retinopathy produced a rise in growth hormone, while the non-diabetics did not (1.24 +/- 0.6 mU/l). The patients with retinopathy produced more growth hormone than those without at each infusion rate (12.2 +/- 11.5 vs. 2.8 +/- 5.1, p = 0.03; 10.6 +/- 11.1 vs. 1.6 +/- 1.7, p = 0.02; 19.7 +/- 20.6 vs. 4.2 +/- 4.8, p = 0.03). These data confirm that insulin alone can stimulate growth hormone secretion in insulin-dependent diabetics with retinopathy. Evidence is provided indicating that patients with retinopathy produce more growth hormone than those without. PMID- 6242780 TI - Diabetes Outward Bound Mountain Course, Eskdale, Cumbria. AB - Following a successful first British Diabetic Association/Outward Bound Mountain Course in 1981, biannual courses were established for insulin-treated diabetic patients. These mentally and physically demanding courses are intended to encourage young diabetic patients to take active exercise whilst learning how to manage their diabetes under varied conditions. Careful medical supervision and expert instruction with minute attention to safety and constant alertness for hypoglycaemia is essential. This paper details the experience gained during the first three courses. PMID- 6242781 TI - Harnessing resources. PMID- 6242782 TI - The manufacture of diabetic footwear. PMID- 6242783 TI - The adolescent diabetic. PMID- 6242784 TI - Predicting the need for insulin therapy in late onset (40-69 years) diabetes mellitus. AB - A six-year prospective study of 144 newly diagnosed, symptomatic diabetic patients aged 40-69 years showed that 21 (15%) required insulin therapy, commencing 1-61 months after diagnosis. The plasma insulin response to oral glucose was assessed at the time of diagnosis. All 12 patients with very low peak insulin response (less than or equal to 6 mU/l) required insulin therapy. Thirty six patients had an intermediate insulin response (greater than 6 less than or equal to 18 mU/l); of these, 7 with a mean weight 88% (range 73-96%) of average body weight required insulin, while 29 with a mean weight 117% (range 98-158%) of average body weight, did not. Ninety-six patients had a peak insulin response (greater than 18 mU/l); 2 patients whose weights were 96% and 100% of average body weight, required insulin, while the remainder did not. Consideration of initial body weight and peak insulin response provides a useful prediction of the eventual need for insulin. PMID- 6242785 TI - Prostaglandin E1 accelerates subcutaneous insulin absorption in insulin-dependent diabetic patients. AB - The powerful vasodilator, prostaglandin E1 (PGE1), was added to Actrapid insulin to try to accelerate the early phase of subcutaneous insulin absorption through increasing injection site blood flow. Actrapid insulin alone (6U) and insulin containing PGE1 (7.5 X 10(-6) M) were injected on different days into 13 fasting insulin-dependent diabetics. With the insulin/PGE1 mixture, increases in both free and total plasma insulin concentrations were greater at all times up to 120 minutes after injection than with insulin alone, with significant differences in the first 40 minutes. With insulin/PGE1 the area under the total plasma insulin curve increased significantly more rapidly between 80 and 120 minutes. Plasma glucose concentrations fell consistently more rapidly with insulin/PGE1 than with insulin alone although the differences were small (mean fall +/- S.E.M. at 120 minutes: 4.9 +/- 0.5 mmol/l vs 4.0 +/- 0.6; p = 0.02). Addition of local hyperaemic agents to short-acting insulin preparations could be therapeutically useful in hastening insulin entry to the circulation at mealtimes. PMID- 6242786 TI - Newly diagnosed, insulin-dependent diabetes mellitus in elderly patients. AB - Over a two-year period 398 out of 1776 new referrals to a diabetic clinic were newly diagnosed diabetic patients aged 65 years and over. Initial treatment of this group was diet--122 (31%), diet plus oral hypoglycaemic agents--232 (58%) and diet plus insulin--41 (10%). Sixteen (39%) of the group treated initially with insulin died within 3.5 years of diagnosis compared with 21% of the 345 patients treated with diet +/- oral hypoglycaemic agents who were followed for this time. Twenty-five patients treated initially with insulin survive but 8 have stopped insulin and are treated with diet +/- oral hypoglycaemic agents, and a further 5 had a period of 6-24 months on oral therapy. Twelve patients have been treated with insulin continuously but of these only 3 are clearly insulin dependent. These data suggest that true dependence on insulin is uncommon in patients aged 65 years or over at diagnosis. PMID- 6242787 TI - Pancreatic cancer and diabetes mellitus. AB - In a series of 6,500 patients with diabetes mellitus there were 37 cases of primary carcinoma of the pancreas which significantly exceeded the expected number for the patient years at risk in both males and females (p less than 0.01). There was no evidence that pancreatic cancer was more common in patients with long-standing diabetes. The increased incidence of pancreatic cancer in diabetic patients is probably the result of patients presenting with the symptoms of diabetes as long as four years before the cancer becomes manifest. An underlying pancreatic tumour should be suspected when an elderly diabetic proves difficult to control and loses weight despite adequate treatment. PMID- 6242788 TI - Diabetes and insurance: a survey of patient experience. AB - A survey of 186 diabetic patients examined their collective experience of life and motor insurance. Some form of life insurance policy had been obtained by 150 patients, with a combined total of 204 policies, 107 of which had been agreed before the diagnosis of diabetes. Most patients had declared diabetes to the insurer but 12 patients had been refused acceptance. Only 15 patients sought alternative quotations. The premium had been loaded by 10-40% for 36 patients because of diabetes, and 48 required a medical report. Of 147 diabetic drivers, 95 (65%) had declared diabetes either to the Licensing authority, or to the motor insurer, but only 62 (42%) had informed both. Fourteen patients had been refused motor insurance cover by individual companies, and 36 patients were aware of having had their premium increased, but only 16 patients had sought alternative quotations. Major differences in attitude with regard to diabetes as a risk factor for insurance are evident, and patients should be advised to approach several companies when seeking insurance cover. PMID- 6242790 TI - The need for a new professional body; is there a role for the BDA? PMID- 6242789 TI - Medical staff in training to become consultant physicians with an interest in diabetes. AB - A census in 1982 of 44 registrars and 66 senior registrars each of whom intends to become a 'consultant with an interest in diabetes' revealed that the training posts are geared to produce the 11 consultants appointments per year which currently become available. However, on top of this 'ladder' are 26 senior registrars who are already due for a consultant post. This backlog would appear to be a permanent feature unless extra new consultant posts become available. A newly appointed senior registrar can anticipate an average of 6 years before a consultant appointment. The majority of junior staff approved the current regulations and training programmes, although 87% felt that they received insufficient guidance. PMID- 6242791 TI - The use of fixed-mixture insulins in the treatment of diabetes. PMID- 6242792 TI - Normoglycaemic re-entry and diabetic complications. PMID- 6242793 TI - Aldose reductase inhibition in diabetes. PMID- 6242794 TI - Fructosamine (glycosylated protein) and the diagnosis of diabetes. PMID- 6242795 TI - Continuous intraperitoneal insulin infusion in the management of severely brittle diabetes--a metabolic and clinical comparison with intravenous infusion. AB - We report a comparison of continuous intraperitoneal insulin infusion (CIPII) and continuous intravenous insulin infusion (CIVII) in 6 diabetic patients in whom severe hyperglycaemia and ketoacidosis could not be prevented with subcutaneous or intramuscular insulin. In the short term both methods were equally effective in maintaining glycaemic control. Blood glucose, glycerol, and 3-hydroxybutyrate levels were normal but lactate and pyruvate levels remained elevated with both treatments. Insulin requirements were significantly lower on CIPII than CIVII (70 vs 113 U/day, p less than 0.01). Intraperitoneal insulin delivery was associated with near physiological peripheral plasma insulin profiles in 3 patients. In the longer term CIVII was associated with frequent septicaemia and thrombosis, and was successful in preventing hospitalization for 6 months or more in only one patient. Despite technical problems with CIPII complications were less serious and hospital admission due to metabolic decompensation was prevented for 6 months or more in 3 patients. When subcutaneous insulin delivery is unsuccessful in the management of brittle diabetes, CIPII should be considered rather than CIVII because it is more likely to be successful and less likely to cause serious complications. PMID- 6242796 TI - Insulin receptor assays--clinical application and limitations (2). PMID- 6242797 TI - Lawrence lecture. Lines to legumes: changing concepts of diabetic diets. PMID- 6242798 TI - Seven years experience of home management in pregnancy in women with insulin dependent diabetes. AB - Fifty-eight of a consecutive series of 75 pregnancies in women with insulin dependent diabetes went into the third trimester. Diabetes was managed by home blood glucose monitoring and women were not routinely admitted at any stage before delivery. The mean number of in-patient days before delivery was 15 for the whole series but has been reduced to 9 during the past four years. Each woman performed an average of 171 blood glucose measurements during her pregnancy. Mean blood glucose (including post-prandial levels) fell significantly from 7.9 mmol/l in the first trimester to 7.3 in the second and 6.4 in the third. Mean percentage of haemoglobin A1 was within the normal range in the second and third trimesters. The cesarean section rate was high at 66% but there were no perinatal deaths. Three infants had congenital abnormalities. We conclude that home blood glucose monitoring is a safe and effective way of managing pregnant diabetic women as out patients. The cost of meters and sticks is repaid many times over in the saving of hospital costs. In addition, home blood glucose monitoring is popular with the patients and many choose to continue it after delivery. PMID- 6242800 TI - Development of scales to measure perceived control of diabetes mellitus and diabetes-related health beliefs. AB - A series of scales was designed to measure perceived control of diabetes and diabetes-related health beliefs with a view to predicting treatment preferences and individual differences in response to the treatments. Scale development is described and the psychometric properties examined with responses from 286 insulin requiring adult diabetic patients. Patients were significantly more likely (p less than 0.001) to attribute responsibility for their diabetes control to themselves rather than to their medical advisors or to other factors. For most of the patients the benefits of treatment were perceived substantially to outweight any barriers (p less than 0.001). Compared with their perceptions of vulnerability to disorders unrelated to diabetes, patients thought that they were more vulnerable to such diabetes related complications as eye, kidney and foot problems (p less than 0.001) but not to heart disease. PMID- 6242799 TI - Evidence for a central abnormality in the regulation of growth hormone secretion in insulin-dependent diabetes. AB - To assess pituitary and hypothalamic function in diabetes, 100 micrograms growth hormone releasing factor 1-44 was administered to 10 normal subjects at fasting plasma glucose (5.2 +/- 0.1 mmol/l, mean +/- S.E.M.), 10 insulin-dependent diabetics while euglycaemic (6.4 +/- 0.3 mmol/l), and 10 while hyperglycaemic (13.1 +/- 1.3 mmol/l). Six of the diabetics participated in both parts of the study. The normal subjects and euglycaemic diabetics produced similar peaks in growth hormone (118.2 +/- 37.6 vs 105.2 +/- 23.9 mU/l, p = 0.69). The peak growth hormone level was reached between 30 and 45 minutes in all the normal subjects, but varied between 15 and 75 minutes in the diabetics. While all normal subjects suppress their growth hormone response to releasing factor when hyperglycaemic, not all the diabetics did so, and the suppression did not reach statistical significance on comparison of euglycaemic and hyperglycaemic diabetics (105.2 +/- 23.9 vs 64.7 +/- 19.4 mU/l, p = 0.2). Comparison of results from those diabetics studied at both euglycaemia and hyperglycaemia again showed no significant difference (140.8 +/- 30.9 vs 90.2 +/- 27.7 mU/l, p = 0.22). These results suggest a central, possibly hypothalamic, abnormality to account for the disruption of growth hormone regulation in diabetes. PMID- 6242801 TI - Pharmacokinetics of human insulin zinc suspension (recombinant DNA) in normal man: a comparison with porcine insulin zinc suspension. AB - A single dose crossover study in 10 fasting, non-diabetic men compared the 24 hour profiles of blood glucose, plasma insulin, and C-peptide following a single subcutaneous injection of either human insulin zinc suspension crystalline (recombinant DNA), or highly purified porcine insulin zinc suspension (mixed), in a standard dose of 0.2 U/kg. Both insulins produced moderate hypoglycaemia within 3 hours which persisted for 24 hours after administration. The rate of fall of blood glucose was similar from 0-3 hours but was significantly lower after the porcine insulin at 4 and 7 hours (p less than 0.05). Mean plasma insulin values were higher after porcine insulin between 2 and 6 hours (p less than 0.05) and a biphasic pattern was observed following injection of both insulins. Plasma C peptide declined after each insulin was administered, and was significantly lower between 2 and 7 hours after porcine insulin. The duration of the hypoglycaemic action of human crystalline insulin (recombinant DNA), assessed by blood glucose measurements and C-peptide suppression, was equivalent to porcine insulin zinc suspension (mixed) (Monotard MC, Novo) over 24 hours. PMID- 6242802 TI - Continuous blood glucose monitoring: a preview. PMID- 6242803 TI - BM strips: how accurate are they in general wards? AB - In order to test the accuracy of BM Test Glycemie 20-800 strips when used in general wards, simultaneous BM strip results were obtained for 183 emergency out of-hours plasma glucose requests. The results were considered accurate if the value obtained by the Emergency Biochemistry Laboratory (using a Beckman II glucose analyser) was within one strip-range on either side of the stated BM strip value. Fifty-nine (32.2%) of the BM strip results were considered inaccurate by this definition, and in 22 of these inaccurate results the differences were large enough to have led to inappropriate management if this was based on the BM strip result alone. The reasons for these inaccuracies are not clear, but it is suggested that improved training of ward staff and formal quality control schemes may help to improve results. PMID- 6242804 TI - Young diabetics: memories, current lifestyles and attitudes. AB - Eighty-six subjects aged 22.3 +/- 2.3 years (mean +/- S.D.), who attended one clinic as diabetic children, filled in a questionnaire designed to evaluate their present health and lifestyles, as well as discover their childhood memories. About two-thirds (66.3%) had unhappy recollections particularly of such irritating routines as urine testing, injections, and special food programmes. Only 6% complained that future complications were not discussed with the child at the appropriate time, but with the exception of blindness, childhood knowledge of diabetic complications was poor. Around two-thirds (66.4%) left school with some examination result; 44.2% went into further education, while 19.8% entered into a trade. These attainments were comparable to those of local school leavers. As young diabetic adults, 62.8% were employed; 22.1% were students or housewives with no other occupations. PMID- 6242805 TI - Right off diabetes. PMID- 6242806 TI - Diabetic education: a physician's view--who, what, where, when and how. PMID- 6242807 TI - Identification card for pump treated patients. PMID- 6242808 TI - The point of no-return for the diabetic kidney is beyond clinical proteinuria. PMID- 6242809 TI - Comparison of glucose control using U80 and U100 strength insulin. PMID- 6242810 TI - Mixed insulins and insulin regimens. PMID- 6242812 TI - What high-risk personnel need to know about the hepatitis B vaccine. PMID- 6242811 TI - Jaw wiring for obesity in insulin-dependent diabetes. PMID- 6242813 TI - The insulin receptor--its function and its fate (2). PMID- 6242814 TI - Pancreatic endocrine-exocrine function in diabetes: an old alliance disturbed. PMID- 6242815 TI - A feasibility study of the use of continuous subcutaneous insulin infusion in a diabetic clinic: patients' choice of treatment. AB - Insulin-treated diabetic patients attending a busy diabetic clinic were approached to determine their interest in using continuous subcutaneous insulin infusion (CSII) via a portable pump. Three hundred and eighty-two patients were offered the choice of CSII, intensified conventional therapy (ICT) or continuation of less intensified treatment. One hundred and sixteen patients (30.4%) chose CSII, 169 (44.2%) chose ICT, 97 (25.4%) chose the less intensive regimen. Those choosing CSII represented a broad cross section of the clinic population, though older patients with a longer duration of diabetes tended to continue with less intensified therapy. There were no differences between groups in the level of blood glucose control or the prevalence of complications at the outset of the study. Of 104 patients not previously using CSII, 86 have so far commenced the therapy. Twenty-seven (32.6%) of these discontinued within one year, 23 doing so in the first three months of treatment. Metabolic control, assessed by glycosylated haemoglobin, was significantly improved in the CSII group after three months and in the other treatment groups by six months. Glycosylated haemoglobin levels achieved with CSII were significantly lower at three and six months when compared with the other treatments. PMID- 6242816 TI - Insulin action and pharmacokinetics in insulin treated diabetics during the third trimester of pregnancy. AB - Insulin action and pharmacokinetics were compared, using the euglycaemic insulin clamp technique, in seven insulin-treated diabetics during the third trimester of pregnancy and one to three weeks post-partum. At an insulin infusion rate of 1 mU/kg/min, insulin mediated glucose disposal was significantly greater (p less than 0.02) following delivery (1.194 +/- 0.138 mmol/m2/min) than in pregnancy (0.761 +/- 0.072 mmol/m2/min) and the rate of decline in insulin mediated glucose disposal, at the end of the insulin infusion, was significantly greater (p less than 0.02) following delivery (24.78 +/- 4.22 mumol/m2/min2) than in pregnancy (15.17 +/- 2.00 mumol/m2/min2). The metabolic clearance rate, distribution space and pharmacological half-life of insulin were not significantly altered by pregnancy. These findings show that the third trimester of pregnancy is associated with steady state insulin resistance accompanied by a reduced rate of insulin deactivation, but normal insulin pharmacokinetics. PMID- 6242817 TI - The Whitehall Study: ten year follow-up report on men with impaired glucose tolerance with reference to worsening to diabetes and predictors of death. AB - Two-hundred and four men with a defined degree of impaired glucose tolerance derived from the Whitehall Survey and its pilot study were enrolled in a therapeutic trial and followed for ten years. For the first five years of the trial approximately half the group received 50 mg phenformin daily and the other half an identical placebo. For the whole ten years of the trial approximately half the group were recommended a diet in which carbohydrate intake was limited to 120 g/day, while the other half was recommended a qualitative limitation of sugar intake. 60 men (29.4%) worsened to diabetes during the follow-up period. The major independent predictor of worsening was the baseline blood glucose level (glucose tolerance). High baseline plasma triglyceride levels and low baseline systolic blood pressure levels were also independent predictors of worsening, though of lower significance (0.01 less than p less than 0.05). Obesity, measured as body mass index, was not a significant risk factor. Thirty-nine men died, with 19 deaths ascribed to coronary heart disease (CHD). Baseline blood pressure significantly predicted both all causes and CHD mortality. All causes mortality rates were higher in the less obese. Allocation to drug or diet therapy did not significantly affect mortality rates or the proportions worsening to diabetes. PMID- 6242818 TI - Plasma C-peptide levels identify insulin-treated diabetic patients suitable for oral hypoglycaemic therapy. AB - Plasma C-peptide levels were measured fasting and 2 h after an oral glucose load in 37 insulin-treated diabetic patients to assess their clinical value in identifying any noninsulin-dependent diabetic patients. All subjects were changed from insulin to oral hypoglycaemic therapy and followed for 3 months. Twenty patients (group A) completed the trial without requiring insulin and 17 (group B) required restabilization on insulin due to deteriorating metabolic control. Fasting and 2 h C-peptide levels were significantly higher in group A (0.11 +/- 0.09 and 0.17 +/- 0.12 nmol/l; mean +/- S.D.) compared with group B (0.02 +/- 0.03 and 0.02 +/- 0.03 nmol/l) (p less than 0.002 and p less than 0.002). The fasting C-peptide levels at 3 months (0.28 +/- 0.14 nmol/l) were also significantly higher than the fasting levels at the beginning of the study (p less than 0.002). Fasting and 2-h glucose levels were lower in group A (11.0 +/- 3.7 and 17.6 +/- 5.2 mmol/l) than in group B (14.4 +/- 6.2 and 23.1 +/- 5.9 mmol/l; p less than 0.05 and 0.02, respectively). The differences in glycosylated haemoglobin and fasting glucose levels at the start of the study and after 3 months of oral therapy were not statistically significant. Although C-peptide values overlapped in groups A and B, they were of greater value in identifying patients suitable for oral therapy than any single clinical criterion, and thus may help in identifying insulin-treated diabetic patients who may be treated with oral therapy without deterioration in metabolic control. PMID- 6242819 TI - Urinary insulin excretion rate: an index of free insulinaemia in insulin dependent diabetics. AB - In 25 insulin-dependent diabetics, 14 managed by conventional insulin injection treatment (CIT) and 11 treated by continuous subcutaneous insulin infusion (CSII), there was a highly significant correlation between urinary insulin excretion rate (IER) per 1.73 m2 and mean serum free insulin concentration (r = 0.73, p less than 0.001), measured over a 24 h period. Urinary IER and mean daily serum free insulin levels were significantly higher in diabetics than in non diabetics. CSII-treated patients had significantly lower mean 24 h plasma glucose levels than CIT-treated patients despite similar values of urinary IER and mean daily serum free insulin in the two groups. Urinary IER may be a useful indicator of average insulinaemia in large scale studies, avoiding the problems of multiple blood sampling and immunoassay in the presence of anti-insulin antibodies. PMID- 6242820 TI - Diagnostic value of the Valsalva ratio reduction in diabetic autonomic neuropathy: use of an age-related normal range. AB - A curvilinear age-related normal range for the Valsalva ratio is presented. Application of this range was used to identify abnormalities in ratios obtained from 59 patients with diabetes mellitus aged 16-60 years. It was found that 35 had normal, 6 had borderline and 18 had abnormal results. Comparison with other autonomic function tests of the cardiovascular and pupillary systems showed that abnormalities of the Valsalva ratio correlated most highly with the sinus arrhythmia test results. Repeat measurements of ratios in healthy and diabetic subjects yielded coefficients of variation of 15.4% and 10.5% respectively. PMID- 6242821 TI - Assay of microalbuminuria using gel electroimmunoassay. AB - The possibility of using electroimmunoassay as a technique for assessing microalbuminuria in the diabetic population has been studied. The method was found to be precise (given inter-batch coefficients of variation of 5.7% and 5.8% at levels of 16 mg/l and 23 mg/l respectively), showed adequate sensitivity, and produced results which correlated well (r = 0.971) with these obtained from a routine radioimmunoassay procedure. It is concluded that electroimmunoassay provides a reliable alternative to more sophisticated techniques in the non specialized laboratory dealing with only moderate numbers of specimens. PMID- 6242822 TI - A simple diabetic clinic information and audit system. AB - A simple method for managing the records of a diabetic clinic in a District General Hospital is described. It is based on a modified manual system in which selected items of data are recorded in a computer system. This provides a Diabetic Register, information for patient and clinical management and for research projects. It simplifies the management of the clinic, is easily used by medical staff inexperienced in the use of computers and causes minimal increase in the clinic workload. PMID- 6242823 TI - Diabetes mellitus: diagnostic criteria. Recommendations of the European Diabetes Epidemiology Study Group (EDESG) concerning the Second Report of the WHO Expert Committee on Diabetes Mellitus. PMID- 6242824 TI - Computer based learning and assessment for diabetic patients. AB - A comparatively inexpensive microcomputer-based system of programmed diabetic instruction is described, matched to an interactive knowledge assessment questionnaire with or without prescriptive feedback. This provides an educational and assessment package for newly diagnosed and established diabetics, with additional analytical potential. The system is well accepted, demonstrates major areas of defective knowledge and allows cost-effective handling of large numbers of patients. PMID- 6242825 TI - Diabetes under your control: microcomputer quiz--a pilot study. PMID- 6242826 TI - Diabetic versus diabetes. PMID- 6242827 TI - Cellular and extracellular siderophores of Aspergillus nidulans and Penicillium chrysogenum. AB - Aspergillus nidulans and Penicillium chrysogenum produce specific cellular siderophores in addition to the well-known siderophores of the culture medium. Since this was found previously in Neurospora crassa, it is probably generally true for filamentous ascomycetes. The cellular siderophore of A. nidulans is ferricrocin; that of P. chrysogenum is ferrichrome. A. nidulans also contains triacetylfusigen, a siderophore without apparent biological activity. Conidia of both species lose siderophores at high salt concentrations and become siderophore dependent. This has also been found in N. crassa, where lowering of the water activity has been shown to be the causal factor. We used an assay procedure based on this dependency to reexamine the extracellular siderophores of these species. During rapid mycelial growth, both A. nidulans and P. chrysogenum produced two highly active, unidentified siderophores which were later replaced by a less active or inactive product--coprogen in the case of P. chrysogenum and triacetylfusigen in the case of A. nidulans. N. crassa secreted coprogen only. Fungal siderophore metabolism is varied and complex. PMID- 6242829 TI - The handicapped child and his family. PMID- 6242828 TI - Heat-sensitive mutant strain of Neurospora crassa, 4M(t), conditionally defective in 25S ribosomal ribonucleic acid production. AB - A heat-sensitive mutant strain of Neurospora crassa, 4M(t), was studied in an attempt to define its molecular lesion. The mutant strain is inhibited in conidial germination and mycelial extension at the nonpermissive temperature (37 degrees C). Macromolecular synthesis studies showed that both ribonucleic acid (RNA) and protein syntheses are inhibited when 4-h cultures are shifted from 20 to 37 degrees C. Density gradient analysis of ribosomal subunits made at 37 degrees C indicated that strain 4M(t) is deficient in the accumulation of 60S ribosomal subunits in that the ratio of 60S/37S subunits was 0.29:1 compared with 1.6:1 for the parental strain. This phenotype was shown to be the result of a slow rate of processing of, and a deficiency in the amount of, the immediate precursor to 25S ribosomal RNA (the large RNA of the 60S subunit) in the sequence of events constituting the production of mature ribosomal RNAs from the primary transcript of the ribosomal deoxyribonucleic acid, the precursor ribosomal RNA molecule. Analysis of polysomes suggested that the heat-sensitive gene product might function in both the assembly and the function of the 60S ribosomal subunit, since there was a smaller proportion of newly made 60S subunits synthesized at 37 degrees C in the polysome region of the gradients than in the monosome-plus-subunit region. The ribosomal RNA processing defect is apparently responsible for the observed defects in germination and macromolecular synthesis at 37 degrees C, but the precise molecular lesion is not known. On the basis of these results, the heat-sensitive mutant allele in the 4M(t) strain is considered to define the rip1 (ribosome production) gene locus. PMID- 6242830 TI - The newly handicapped adolescent. PMID- 6242831 TI - Towards independence. PMID- 6242832 TI - Sexual and genetic counselling. PMID- 6242833 TI - Major legal/ethical challenges in the care and treatment of the mentally retarded. PMID- 6242834 TI - Major morphological effects of a regulatory gene: Pgm1-t in rainbow trout. AB - We have investigated the morphological effects of a genetic locus, Pgm1-t, that affects the expression of a phosphoglucomutase locus (Pgm1) in liver of rainbow trout (Salmo gairdneri). We have previously shown that embryos with liver Pgm1 expression hatch earlier than those without liver Pgm1 expression. We predicted that this difference in developmental rate should cause a reduction in meristic counts in the more rapidly developing fish with liver Pgm1 expression. Eight meristic (countable) characters in nine full-sib groups segregating for the presence or absence of liver Pgm1 expression are in agreement with this prediction. In eight of the nine families, there is a significant difference in the multivariate distribution of the eight meristic counts between full sibs with and without liver Pgm1 expression. This separation in multivariate space is based on a tendency for lower meristic counts in fish with liver Pgm1 expression. The magnitude of these morphological differences is similar to that between two subspecies of cutthroat trout (Salmo clarki) that show substantial genetic divergence at structural loci encoding enzymes (Nei's D = 0.34). These data support the view that small changes in the developmental process caused by genetic differences at regulatory genes can have large effects on morphology. PMID- 6242835 TI - Autoantibody probes for mammalian gene expression. PMID- 6242837 TI - [Experimental studies on the embryotoxic effect of phosphamidon on the epithelium of convoluted kidney tubules. II. Histological and histochemical studies]. PMID- 6242836 TI - Do platelets have anything to do with diabetic microvascular disease? AB - It has been postulated that abnormal platelet and endothelial function may contribute to microangiopathy in diabetes mellitus. If this proposal is correct, alterations in platelet and endothelial function should be found before the appearance of vascular disease in insulin-dependent patients and in animal models of diabetes mellitus. This appears to be the case for the following: platelet aggregation, increased platelet production of the proaggregatory prostaglandin metabolite thromboxane, decreased endothelial production of the antiaggregatory prostaglandin prostacyclin, and decreased platelet survival. Insulin therapy will return some of these findings to normal. Platelet-plasma interactions that promote platelet aggregation and increased plasma levels of the platelet-specific protein beta-thromboglobulin have been reported in insulin-dependent diabetic patients who have not manifested vascular complications as well as in those with vascular complications. It has now been demonstrated in animal models that platelet microthrombi are found in small retinal vessels after months of experimental diabetes. Collectively, these findings demonstrate that alterations in platelet and endothelial function that favor thrombosis occur early in the diabetic state and may contribute to microvascular disease. There are several ongoing studies of antiplatelet agents in diabetic vascular disease that will provide clinical evidence bearing on the major postulate. Until these and other studies are completed, the platelet-endothelial story remains an attractive hypothesis in the genesis of diabetic microvascular disease. PMID- 6242838 TI - [Research of periodontal disease in the infirmaries for severely disabled patients in Miyagi prefecture]. PMID- 6242839 TI - [Flow characteristics of Bis-GMA composite resin]. PMID- 6242841 TI - Influence of ethanol and acetaldehyde on fibrinolytic system (examinations in vitro). PMID- 6242842 TI - Biological response to a musculo-tendinous prosthesis in the rabbit. PMID- 6242843 TI - Preclinical evaluation of knitted radiation graft copolymer elastomeric vascular prostheses. PMID- 6242844 TI - Lambda exonuclease. PMID- 6242845 TI - New pharmacological aspects of the bronchodilating activity of procaterol. AB - The selectivity of procaterol for beta 2-adrenoceptors vs beta 1-adrenoceptors in animals has been already described. In these studies the ability of procaterol to protect guinea-pig against bronchoconstriction induced by various spasmogens such as histamine, LTC4 and acetylcholine is demonstrated. The results obtained both in anaesthetized animals and in perfused lungs clearly show that procaterol antagonizes not only the direct effect of the bronchoconstrictors quoted above but also their ability to activate arachidonic acid metabolism and to augment the generation of TXA2. Procaterol (0, 3-3 micrograms/Kg i.v.) is more potent than salbutamol in protecting passively sensitized guinea-pig from massive bronchoconstriction following antigen challenge: a phenomenon which is paralleled by an increment of the circulating TXA2. The possibility that the adenylate cyclase-stimulating properties of procaterol may explain its antiasthmatic activity is discussed. PMID- 6242846 TI - Catecholamine and cortisol responses to sufentanil-O2 and alfentanil-O2 anaesthesia during coronary artery surgery. AB - The effects of alfentanil-O2 and sufentanil-O2 anaesthesia on plasma catecholamines and cortisol were investigated in 32 patients undergoing coronary artery bypass grafting operations. After lorazepam-atropine premedication and pancuronium pretreatment, alfentanil was given to 16 patients at a rate of 3 mg.min-1 and sufentanil was given to 16 patients at 300 micrograms.min-1 until the patients were unconscious; at this time they were given succinylcholine and were intubated. After intubation an amount of alfentanil or sufentanil equal to the dose producing unconsciousness was infused over the next 30 min, at which time the operation began. Additional alfentanil or sufentanil were given whenever systolic arterial blood pressure increased more than 15 per cent of preanaesthetic values. Arterial blood samples were obtained for epinephrine, norepinephrine and cortisol assay and cardiovascular dynamics were recorded prior to anaesthetic induction, 5 min after tracheal intubation, immediately prior to and five min after incision, ten min after maximal sternal spread, just prior to beginning and after 30 and 60 min of bypass and at the end of operation. Cardiovascular dynamics were little changed throughout anaesthesia and operation. Plasma epinephrine and norepinephrine were not significantly changed until bypass. During bypass both hormones became increased and remained increased at the end of operation. Plasma cortisol decreased after incision and remained decreased until the end of operation. These data indicate that alfentanil-O2 and sufentanil-O2 anaesthesia produce similar changes in plasma catecholamines and cortisol as does fentanyl-O2 anaesthesia and hormonal effects are, therefore, not an explanation for any advantages the newer narcotics may have over fentanyl. PMID- 6242847 TI - [Genetic control of mixed lymphocyte culture]. AB - Eighteen healthy families were HLA typed with highly specific cytotoxic antisera; 10 of them were also HLA-DR typed. All of them were tested in the mixed lymphocyte culture. Two different methods of mixed lymphocyte culture-with respect to the number of cells used-were compared. The influence of D and DR antigens on mixed lymphocyte culture is discussed. A rather rare finding was that two unrelated people were homozygous for DR, but not for D and, hence, different with respect to their D and DR antigens. Seven individuals, among them two pairs of identical siblings, were found to be homozygous for HLA-D and HLA-DR. The possibility of using them as typing cells for the alleles of the HLA-D locus was discussed. PMID- 6242848 TI - Discrimination of 2 types of suppressor T cells by cell surface phenotype and by function: the ability to regulate the contrasuppressor circuit. AB - Contrasuppression is an immunoregulatory T cell activity that augments immune responses by interfering with suppressor T cell function. Since contrasuppression appears to play a role in autoimmunity, hyperimmunity, and recovery from induced general unresponsiveness (such as appears following burn trauma), an understanding of how contrasuppression is controlled may have profound implications for understanding immune regulation as well as for manipulating immune responses. Further, since inhibition of contrasuppressor function would appear as suppression, identifying cells able to perform this function would describe at least two modes of suppression in immune regulation, and allow a synthesis of regulatory T cell circuits not previously possible. In the studies described, we have sought to identify distinct lymphocyte subpopulation(s) having the specialized activity of regulating the cells of the contrasuppressor circuit. Two experimental systems have been previously examined. In the first, cells regulating the appearance of contrasuppressor effector T cells generated in cultures of neonatal spleen cells have been characterized. In the second, cells producing a contrasuppressor inducer factor derived from antigen-stimulated Ly-2 T cells have been studied, as well as their cellular targets. Regulation of contrasuppressor T cell activation in both systems by various cell populations was characterized by means of antisera against cell surface differentiation antigens. Our studies demonstrate that an I-J+, Ly-1,2 cell whose activity is not apparent before 1-2 weeks postbirth appears in adult T cell populations and regulates the generation of contrasuppressor cells in neonatal cell cultures. This adult cell can be removed with a low concentration of a monoclonal anti-T cell reagent. Removal of these T cells from adult populations allows the generation of an adult contrasuppressor effector cell indistinguishable from the one found in neonatal spleen by means of the spleen cell culture system. Adult antigen-primed Ly-2 T cells, used for the production of suppressor factor, contain a cell sensitive to the monoclonal antibody that normally prevents the dominance of contrasuppression over suppression. We refer to this cell as a "level 2" suppressor because after its removal contrasuppression is found, and after this contrasuppression is eliminated by selective antiserum treatment suppression is observed. This indicates that a "level 1" suppressor exists, but effector factors mediating this suppression are significantly more susceptible to contrasuppression than are those of "level 2" suppressor cells. Our findings demonstrate two types of suppressor cell circuits PMID- 6242849 TI - A cloned, antigen-specific, Ia-restricted Lyt-1+,2- T cell with suppressive activity. AB - The correlation between cell surface antigen phenotype and function is one of the cornerstones of modern cellular and clinical immunology. It is based on the collective experience of many investigators examining populations of T cells. The availability of cloned lines of T cells now allows us to ask whether all cells sharing cell surface antigen phenotype are functionally equivalent. We have examined a large number of antigen-specific, self-Ia recognizing, cloned Lyt-1+,2 T cell lines for their ability to help B cells proliferate and secrete antibody in response to antigen. All of these lines induced antigen-specific, Ia restricted B cell proliferation. One line did not induce antibody secretion. This line, indeed suppressed the plaque-forming cell response of B cells helped by any of the other cloned T cell lines tested. Suppression in this system had all the characteristics of classical T cell help, apart from the ultimate outcome. That is, the suppressor cell acted upon the B cell in a manner that was antigen specific, Ia-restricted, and required hapten-carrier linkage. We interpret our results as supporting the basic paradigm of an association of cell surface antigen phenotype with function, with an important proviso. Not all Ly1, Ia restricted T cells may be capable of helper function, and some in fact may be suppressive. Experimental conditions favoring the generation of such cells, or disease states in which such cells reside within the Ly1 or T4+ subset, may give rise to disparities between phenotype and function similar to that observed here at the clonal level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 6242850 TI - Enhancement of B lymphocyte secretory differentiation by a Ly 1+,2-,Qa-1+ helper T cell subset that sees both antigen and determinants on immunoglobulin. AB - The question of how many helper T cells are required for producing optimal antibody responses and what function each of the candidate helper cells performs are subjects of intense interest (and controversy) to the majority of immunologists. Our manuscript directly demonstrates for the first time that B cell clone growth and secretory differentiation are controlled by two distinct classes of helper T cells which can be discriminated from one another by profiles of their expressed cell surface alloantigens. There is a significant amount of inferential evidence that two types of helper T cells are required to interact with B cells and antigen in order to induce maximal antibody responses. In all reports, classical MHC-restricted, carrier-specific helper T cells (TH 1) had to interact with hapten-specific B cells via carrier-hapten bridges before the second helper cell (TH 2) could act. In contrast to the TH 1 cells, TH 2 cells have been reported neither to be MHC-restricted nor to require carrier-hapten bridges in their interaction with hapten-specific B cells. That certain isotype-, allotype-, or idiotype-expressing portions of the antigen-induced antibody response are preferentially enhanced in the presence of and depleted in the absence of the appropriate TH 2 cells has led to the suggestion that such TH 2 cells interact with B cells through receptors specific for determinants expressed on B cell surface immunoglobulin molecules. That TH 2 cells recognize autologous immunoglobulin determinants is also indirectly supported by their reported absence in appropriately immunized mice which were deficient in the relevant immunoglobulin during ontogeny [e.g. all TH 2 cells in anti-mu-treated mice; T15 specific TH 2 cells in (CBA/N X BALB/c)F1 male Xid mice which lack T15+ B cells]. It has been suggested that TH 2 cells recognize not only autologous immunoglobulin determinants but also "nominal" antigen since they have been reported to be dependent on antigen priming and reexposure to the priming antigen. However, to establish firmly that a TH 2 cell expresses receptors for both antigen and Ig determinants, one must isolate that helper cell by virtue of its receptor for one of these two moieties and show that the isolated cell has receptors for the other. We have done this, as well as showing that the Ig recognizing, carrier-immune T cell selectively enhanced B cell secretory differentiation while having no effect on clonal expansion.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 6242851 TI - Idiotype-specific T cell suppression of light chain mRNA expression in MOPC-315 cells is accompanied by a posttranscriptional inhibition of heavy chain expression. AB - Earlier studies have shown that idiotype-specific T suppressor cells can directly inhibit the biosynthesis and subsequent secretion of immunoglobulin from the BALB/c myeloma, MOPC-315. This suppression is highly specific and does not affect nonimmunoglobulin protein synthesis in these cells. The selective character of this suppression suggested a transcriptional or translational mechanism of control. Therefore, we analyzed suppressed MOPC-315 cells for the expression of light and heavy chain mRNAs. Since the events that occur in a B cell subsequent to reception of suppressive signals from T cells are presently unknown, these experiments address a fundamental aspect of B cell regulation. Another important aspect of these studies is that they deal with a suppressor T cell that clearly operates directly upon the antibody-secreting cell. This system involves regulation of a B cell differentiative function without influencing the B cell clonal size. We have employed the trinitrophenyl (TNP)-specific myeloma, MOPC 315, because it provides a source of monoclonal B cells which in earlier studies have been shown to be responsive to idiotype-specific and TNP-antigen-specific immunoregulatory signals. The idiotype-specific T cells were generated by hyperimmunizing BALB/c mice with the myeloma protein bearing the 315 idiotype, in complete Freund's adjuvant. Poly A+ mRNA was isolated from MOPC-315 cells following coculture with either normal or idiotype-immune T cells. The mRNA was analyzed using hybridization techniques and cDNA probes specific for alpha or lambda 2 light chain constant regions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 6242852 TI - Helper functions of antigen-induced specific and autoreactive T cell colonies. AB - Helper T cells have been distinguished on the basis of whether they provide carrier-specific or nonspecific helper functions. In previous experiments we determined that the predominant class of helper T cell in populations of primed lymph node cells is a nonspecific helper T cell unable to provide carrier specific signals. Initial induction of nonspecific helper T cells in vitro requires restimulation with the immunogen. This suggested that such T cells may express antigen-specific receptors. In this case they would constitute a unique subpopulation distinct from T cells with identical antigen-specificity that are able to provide carrier-specific help. Alternatively, the requirement for antigen restimulation might reflect a role for antigen-specific T cells in the recruitment of T cells with unrelated specificity. To distinguish between these possibilities we have characterized the specificity and function of helper T cell colonies selected from primed lymph node cells. We report here isolation of autoreactive as well as antigen-specific helper T cells. All antigen-specific T cell colonies provide carrier-specific help in the presence of the homologous hapten-carrier conjugate. Only autoreactive T cells are limited to providing nonspecific helper function. Although selection of autoreactive T cells is initially dependent on antigen restimulation in vitro, activation of an established autoreactive T cell line requires restimulation with MHC-syngeneic spleen cells but does not require restimulation with either the immunogen or fetal calf serum. These results suggest that nonspecific helper T cells induced in the course of a normal immune response to randomly chosen foreign antigens are autoreactive. Such T cells may serve to enhance proliferation and maturation to immunoglobulin secretion of B cells activated by limiting numbers of carrier specific helper T cells. The demonstration of large numbers of precursors to MHC specific autoreactive T cells in antigen-primed populations raises important issues concerning regulation of the expansion of autoreactive T cells in vivo. PMID- 6242853 TI - The IgE antibody system: mature, peripheral B lymphocytes exert regulatory influences on the IgE systems of self-reconstituting, sublethally irradiated mice. AB - Previous studies have documented clear biological differences, such as sensitivity to moderate doses of irradiation, between B lymphocytes of the IgE type and B lymphocytes of other immunoglobulin isotypes. The present experiments were originally designed to explore such differences further by comparing the abilities of B lymphocytes derived from various IgE responder phenotypes, which differ among various inbred mouse strains, to reconstitute in a positive way the ability of sublethally irradiated recipient mice (of syngeneic or semisyngeneic type) to mount specific immune responses of the IgE antibody class. This was an important question with regard to delineating fully underlying differences in IgE responder phenotypes among different mouse strains, since heretofore most of the emphasis in experimentally defining such differences has focused on differences in T cell function, rather than B cell function. The experimental approach chosen to address this question seemed logical for two reasons: 1) it was our expectation that following exposure to the dose of irradiation employed (700 rads), individual mice would only slowly repopulate peripheral lymphoid tissues with their own stem cell products, and hence the expression of IgE responsiveness observed could be expected to reflect the responsiveness of the donor B cell population transferred into such recipients; and 2) since recipient mice were carrier-primed one week prior to irradiation in order to create a pool of radioresistant carrier-specific helper T cells, one could expect that this amplified pool of helper T cells would hasten the development of antibody production by the transferred donor B cells. PMID- 6242854 TI - Acquisition of paralytic activity by inducer cells. AB - Clones of inducer cells activated by antigen and class II major histocompatibility complex (MHC) gene products synthesize large amounts of several distinct mRNA species not detected in other activated cell types, including antigen-activated suppressor or killer cell clones. Although inducer cells continued to synthesize and secrete peptides at about the same rate for 5 days after activation by adherent cells and antigen, they expressed a new set of mRNAs approximately 3 days after activation. We therefore tested the functional activity of purified Ly1 cells at different days after activation by adherent cells and antigen. We wished to find out (a) whether there was a qualitative or quantitative change in the level of inducer activity, and if so, (b) whether this functional change was an intrinsic property of Ly1 cells or, rather, was dependent on signals from the cellular environment, in particular from adherent antigen-presenting cells. We incubated purified Ly1 cells and splenic adherent cells for 1-7 days in vitro, and tested inducer activity in cultures containing highly purified B cells and sheep erythrocytes (SRBC). Anti-SRBC plaqueforming cells were counted 5 days later. We found that inducer cells that have been incubated with adherent cells in culture for more than 72 h (a) did not induce B cells to produce antibody, and (b) prevented virgin but not immune B cells from receiving T-helper signals. We term this latter phenomenon "paralysis." Acquisition of the ability to paralyze virgin B cells required an I-E gene regulated interaction between inducer cells and in vitro-activated adherent cells. This interaction did not require antigen and was associated with transition from Ly1:Qa1- to Ly1:Qa1+ cell-surface phenotype. Taken together these findings indicate that (a) interactions between inducer cells and adherent antigen-presenting cells result first in classical inducer ("helper") activity and later in expression of paralytic activity and (b) sequential expression of these inducer activities depends on two distinct signals, supplied by resting and activated adherent cells, respectively. The signal supplied by autologous activated adherent cells is regulated by I-E gene products and is independent of corecognition of foreign proteins. The physiologic significance of this paralytic inducer activity in the prevention of potentially harmful immune reactions to foreign microbial agents is discussed. PMID- 6242855 TI - Biologically active molecules regulating the IgE antibody system: biochemical and biological comparisons of suppressive factor of allergy (SFA) and enhancing factor of allergy (EFA). AB - Studies in recent years directed at unraveling the complex regulatory mechanisms controlling IgE antibody production have demonstrated the existence of soluble factors that exert selective regulatory effects on the IgE antibody system. In addition, the demonstration of IgE-specific Fc receptors (FcR epsilon) on B and T lymphocytes, especially after exposure to high concentrations of IgE either in vivo or in vitro, has provided increasingly strong indications of an important role for such cells in the overall control of the IgE system. In our own laboratory, we have been studying soluble regulatory factors known as suppressive factor of allergy (SFA) and enhancing factor of allergy (EFA), which were initially identified by their selective, and opposing, regulatory effects on in vivo IgE responses in inbred mice. More recently, in an in vitro system in which it is possible to induce the de novo expression of FcR epsilon on lymphocytes cultured in the presence of monoclonal IgE, we reported that concomitant exposure of such cultured cells to SFA selectively blocked the induction of FcR epsilon expression. In the present study, we have extended these investigations by making a direct comparison between certain biological properties and biochemical characteristics of SFA and EFA. We found that SFA and EFA can be distinguished biochemically on the basis of size, SFA falling in the range of 30,000 daltons or so, and EFA falling in the range of 15,000 daltons. In examining their biological properties, we unexpectedly found that although SFA-enriched and EFA-enriched fractions exert dramatically distinct biological effects on in vivo IgE antibody synthesis (as implied by their names), the two respective active fractions are totally indistinguishable in their inhibitory effects on IgE-mediated induction of FcR epsilon + lymphocytes in vitro when intact spleen cell populations are exposed to monoclonal IgE. That the active entities in SFA and EFA responsible for inhibition of FcR epsilon induction do not exhibit IgE-binding properties was shown by the fact that adsorption on IgE-coupled affinity columns had no appreciable effect on their inhibitory capacities. This distinguishes these molecules from the IgE-binding factors described by Ishizaka and colleagues. Moreover, as previously documented for SFA, we found that EFA neither possesses immunoglobulinlike determinants nor binds to other immunoglobulin class molecules. Finally, chromatographically fractionated EFA was shown to exert its enhancing activity on in vivo IgE antibody production across strain barriers, thereby ruling out any genetic restriction on its functional capacity. A similar absence of genetic PMID- 6242856 TI - B cell-deprived mice lack functional expression of certain T suppressor cell subsets. AB - The generation of functionally active immunoregulatory T lymphocytes has been shown to depend upon the interaction of a number of different immune cell types during development. In order to understand and perhaps manipulate immunoregulatory T cell interactions, it is important to identify the nature and role of these cell types in the immunoregulatory T cell pathway. We have investigated the role of Ig+ B cells in the generation of suppressor T lymphocytes in the immune response to SRBC. Our approach was to suppress the expression of Ig+ B cells in experimental mice by continuously treating these animals with a rabbit anti-mu-chain antiserum. These animals were simultaneously tested for their ability to make suppressor T cell responses as measured by the ability to produce or accept SRBC-specific suppressor T cell factors. This particular approach, neonatal suppression with anti-mu-chain antibody, has been previously shown to be an effective means of depleting animals of Ig+ cells, while having little or no effect on a number of different T cell-mediated responses, including T cell mediated allograft rejection and delayed-type hypersensitivity responses in vivo as well as the generation of MLR and CTL responses to alloantigens and conventional I-A recognizing T helper cell responses in vitro. Our results indicate that anti-mu-treated mice lack the ability to produce both Ly1 and Ly2 cell-derived suppressor factors when immunized with the relevant antigen SRBC. Further, while the T cells from anti-mu treated mice were capable of generating a T helper cell response to SRBC in vitro, these T cells no longer responded to suppressor cell signals from either the Ly1 or Ly2 T cell-derived suppressor factors. The ability to produce or accept suppressor cell signals was traced to the lack of an I-J+ Ly1 T cell absent in anti-mu-treated mice. This cell produces an I-J+ antigen nonspecific molecule which imparts Igh-V linked genetic restrictions to both the Ly1 and Ly2 T cell derived suppressor factors. The results alter our view on immune regulation by suggesting that both the induction and effector phase of suppressor T cell activity to SRBC is dependent upon an antigen nonspecific Ly1 I-J+ T cell which is distinct from the antigen recognizing I-J- T cells required for antigen specific suppression. This I-J+ T cell, which imparts an Igh-linked restriction to the suppressor factors, is critically dependent on Ig+ B cells to reach a functionally active state.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 6242857 TI - Induced differentiation of a B cell lymphoma with known antigen specificity. AB - We have previously described a murine B-cell lymphoma, CH12, the cells of which bear surface IgM reactive with sheep erythrocytes (SRbc) and which could differentiate to secrete hemolytic antibody. The question addressed in this paper was whether differentiation of CH12 cells could be influenced by interaction with regulatory T cells and antigen. If so, we wanted to know whether the conditions required differed from those known to govern similar interactions with normal B cells. We had two reasons for wanting to answer these questions. First, we wondered whether CH12 could be used as a clonal population of indicator cells to study the regulation of B cell differentiation and, second, we wanted to know the extent to which these neoplastic cells were still responsive to normal regulatory signals. The first addresses a major difficulty which must be faced in studies of normal B cell differentiation: to what extent is the interpretation limited by heterogeneity of the B cells used? The second relates to the nature of neoplasia and the possibility that neoplastic cells might be rendered harmless by inducing terminal differentiation. CH12 is one of a series of transplantable B cell lymphomas which arose in B10.H-2aH-4b p/Wts (2a4b) mice, following intense immunization with SRbc. It is a monoclonal tumor, all the cells of which bear membrane IgM(kappa) of a single idiotype, reactive with sheep and chicken Rbc and with bromelain-treated autologous mouse Rbc. The cells express KkAkEk and Dd antigens appropriate to the H-2a haplotype. During the latter stages of growth in vivo or in vitro, a small proportion (less than 3%) of the cells differentiate to secrete hemolytic antibody as measured by the Cunningham assay for plaque forming cells (PFC). We cultured CH12 cells for 3 or 4 days, together with antigen and spleen cells from primed animals, and assayed for PFC induction. Differentiation was induced by spleen cells from SRbc primed 2a4b mice in the presence of SRbc or ChRbc but not rabbit or human erythrocytes. Activity was depleted by treatment of the spleen cells with anti-Thy-1 or anti-Lyt-1 but not anti-Lyt-2 plus complement. Helper cells could also be induced by priming 2a4b mice with ChRbc but not rabbit or human Rbc. Neither of these last two would induce differentiation of CH12, even when both homologous antigen and SRbc were present in the cultures.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 6242858 TI - Mechanisms involved in the Ir-gene control of T suppressor cell response to lactate dehydrogenase B. AB - It has now been widely accepted that the immune response (Ir)-gene control of T helper (Th)-cell responses reflects the influence of class II major histo compatibility complex (MHc) molecules on T-cell specificity. This influence can either be exerted during T-cell ontogeny and result in class II allele-dependent differences in the T-cell repertoire, or manifests itself during the immune response as a restricted capacity of class II molecules to associate with foreign antigens in a form recognizable by Th cells. Depending on the level at which class II Mhc molecules act, the cause of nonresponsiveness to certain antigens can be either the absence of the relevant clones from the T-cell repertoire (as a result of Mhc-dependent positive or negative selection mechanisms), or the incapability of a particular class II molecule to form a complex with a foreign antigen on the surface of antigen presenting cells (APC). It is well known that T suppressor (Ts)-cell responses can also be under Ir-gene control, as reflected in the Mhc-dependence of Ts cell-generation in response to certain antigens. However, the mechanisms involved in this Ir-gene control are less well understood. We have used here the immune response to lactate dehydrogenase B (LDHB) as a model to explore the mechanisms causing absence of suppression ("Ts cell nonresponsiveness"). The LDHB system is suitable to investigate this question, because the LDHB-specific Ts cells are Mhc-restricted, and only two allelic forms, b and k, of the E beta class II polypeptide can serve as restriction elements for Ts-cell generation; mouse strains not expressing these molecules are Ts-cell nonresponders. We applied here the methods previously used to analyse nonresponsiveness of Th cells to the Ts-cell response. The approach was to generate LDHB-specific Ts cells in vitro, by presenting the antigen on Mhc disparate APC (allorestricted Ts cells). The results have demonstrated that Ts cells from two representative Ts-responder strains can be generated in the context of several but not all allogeneic E molecules. The non-responsiveness observed in certain allogeneic T cell-APC combinations could not be explained by defective antigen presentation. Thus, these cases of Ts-cell nonresponsiveness, similar to Th-cell nonresponsiveness, might have resulted from the absence of the relevant T-cell clones from the repertoire of the strain tested.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 6242859 TI - T helper cells required for the in vitro primary antibody response to SRBC are neither SRBC-specific nor MHC-restricted. AB - These studies address the specificity of the T cells which normally function in the in vitro primary immune response. It is generally accepted that SRBC specific, MHC-restricted T helper cells become activated both in vivo and in vitro by seeing erythrocyte antigens presented in the context of the MHC antigens of an antigen-presenting cell. At this point, the in vivo and in vitro systems differ. In vivo, the interaction between SRBC-specific B cells and the activated T helper cells is itself also MHC-restricted, whereas in vitro, the T cell-B cell interaction is not MHC-restricted, and may be factor-mediated. It is the first phase of the in vitro response, and actually the specificity of the T cells which function in the in vitro primary response that we are questioning, in these studies. The experimental approach was to deplete antigen-specific T helper cell activity by passage of T cells through irradiated mice in the presence of a high dose of antigen, and collecting thoracic duct cells one day later. Using this protocol, we have confirmed that removal of SRBC-specific T cells ablates the adoptive transfer in vivo response to SRBC. However, the same negatively selected T cell populations were just as potent as control T cells in supporting the in vitro response to SRBC. We confirmed that the T cells removed respond to SRBC in an MHC-restricted manner by removing from an F1 T cell population the cells able to respond to SRBC in association with one parental haplotype. These T cells nonetheless provided equal help for both parental B cell populations in vitro. These experiments show that the MHC-restricted antigen-specific T cell which is required for the in vivo response is not required in the primary in vitro response to erythrocytes. The significance of this is twofold. Firstly, this demonstrates clearly that different T cells are functioning in vitro vs. in vivo. Singer and his colleagues have shown that different B cell subpopulations (Lyb5+ vs. Lyb5-), with differing MHC-restriction requirements, are preferentially activated in vivo and in vitro. Our data says that another difference between the in vivo and in vitro SRBC response is that different T cells are working in the two systems. Understanding exactly which B cell and T cell subpopulations are working within the model system (in vivo or in vitro) that an investigator chooses is obviously of critical importance.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 6242860 TI - The expression of idiotypic determinants on suppressor T cells is independent of T cell Igh genotype. AB - To investigate the role played by immunoglobulins in the display of idiotope-like determinants by T cells, we investigated whether T cells transferred to congenically athymic mice would display the idiotypes of the nude host or of the T cell donor Igh genotype. 4-Hydroxy-3-nitrophenyl hapten (NP)-specific first order suppressor T cells (Ts1) from Ighb-bearing mice display the NPb idiotype. Mature peripheral T cells from Igh congenic mice were used for reconstitution of nude mice in acute transfers. Before analyzing the idiotypic properties of the T cells in this system, we verified, using Thy-1 congenic strains, that the suppressor T cells induced were effectively derived from the transferred T cells and not from the host. The following strains of mice were selected for these studies: C57BL/6 (Ighb), B6.Ighn, and C57BL nu/nu. The NP-specific suppressor T cells generated in C57BL nu/nu mice reconstituted with T cells derived from Igh congenic B6.Ighn donors were investigated. Suppressor T cells were induced by i.v. administration of 10(4) NP-coupled B6.Ighn adherent cells. Six days later, the spleen cells from the reconstituted nude mice were treated with anti-NPb antibodies and complement before being transferred to C57BL/6 recipients immediately prior to antigen priming. Treatment with anti-idiotypic reagents depleted suppressor cell activity, which indicates that the suppressor cells obtained from C57BL/6 mice or C57BL nu/nu mice that have been reconstituted with B6.Ighn T cells bear NPb idiotype-related determinants. The data further demonstrate that the idiotype-related determinants expressed on NP-specific Ts1 are controlled not by the Ighn genotype of the T cell donor, but by the genotype of the C57BL nu/nu (Ighb) recipient host. In agreement with these findings, we further verified that the NP-specific suppressor T cells generated in C57BL nu/nu mice reconstituted with B6.Ighn mature T cells display the operational Igh restrictions of C57BL/6 mice and not of B6.Ighn mice. These experiments demonstrate how idiotypic elements expressed on the immunoglobulins of the host influence the specificity of the antigen receptor on T cells. Normally, Ts1 from B6.Ighn mice lack the NPb idiotype-related determinants and their suppressive activity is operationally restricted by the Ighn allotype. However, mature B6.Ighn T cells selected to respond to NP in C57BL nu/nu recipients display idiotype-related determinants and restriction specificities characteristic of the C57BL (Ighb) host. Thus, the environment in which Ts1 are induced and selected affects the Ts1 repertoire. How can we account for this phenomenon? PMID- 6242861 TI - Selection of thymocyte MHC restriction specificity in vitro. AB - The thymus is critical for the generation of mature T cells with restricted specificity for major histocompatibility complex (MHC) molecules of thymic genotype. The mechanism by which this T cell commitment to self-MHC gene products occurs in vivo prior to the exposure to foreign antigens is unknown. When thymocytes are cocultured with irradiated syngeneic accessory cells, a proliferation of cells specific for self-Class II MHC molecules is observed. This in vitro response is of interest in the context of the physiologic events that occur in the thymus. However, the functional significance of these in vitro proliferating cells, as well as their relationship to antigen-specific, MHC restricted T cells, has not been defined. Further, whether this in vitro response is capable of influencing the MHC specificity of the thymocytes is unknown. In the work reported here, cells obtained from these cultures were tested for their ability to help a primed B cell antibody response. This approach allowed an analysis of function, antigen and MHC-restriction specificity, and the behavior of these cells upon transfer in vivo. Potent T-helper function was obtained from such cultures for an antigen-dependent, hapten-specific B cell response. When F1 thymocytes were cultured with F1 accessory cells, the T-helper cells recovered could help B cells of both parental MHC haplotypes. However, if the same F1 thymocytes were first cultured with parental accessory cells, they subsequently cooperated only with the corresponding parental or F1 B cells. This MHC restriction was determined by the MHC genotype of the accessory cell in primary culture. Monoclonal antibody blocking studies demonstrated that Ia molecules were critical to this process. Suppression did not account for the observed restrictions. The effector specificity of the T-helper cells could be mapped to the I-A subregion. On adoptive transfer to lethally irradiated hosts, the helper cells could localize to peripheral lymphoid organs. These cells retain their in vitro-imposed restriction specificity even when transferred back to and primed in an F1 environment. Using this experimental protocol, carrier antigen-specific, MHC-restricted priming of these thymic T-helper cells could be detected. These results demonstrate that one can select and amplify functional T-helper cells from cultures of thymocytes whose precise MHC-restriction specificity is determined in vitro. PMID- 6242862 TI - Limiting dilution cultures reveal latent influenza virus-specific helper T cells in virus-primed mice. AB - Although lymphokine producing helper T cells are suspected to play an important role in the development of anti-viral cytotoxicity, they have not previously been demonstrable in influenza virus-primed mice unless the mice have first been pretreated with cyclophosphamide. It has been assumed that cyclophosphamide pretreatment was required to block the activities of suppressor cells which would otherwise interfere with helper T cell priming. We have developed a limiting dilution assay (LDA) for estimating influenza virus-specific T cell precursors for IL-2 secretion ("pHTL"), and have found that equal numbers of pHTL develop in virus-primed mice regardless of cyclophosphamide pretreatment. This result suggests that the cyclophosphamide-sensitive regulatory cells do not act in vivo to prevent helper cell priming, but rather act in vitro to oppose expression of helper cell activity. Comparison of helper cell function in conventional (high density) cultures and in LDA cultures reveals an Lyt-2+ cell which prevents development of cytotoxic function in conventional assays, but which fails to affect the outcome of the LDA experiments. We found that the pHTL population consists almost entirely of Lyt-2- cells, and that mice primed with the Type A strain, PR/8, develop pHTL responsive to a wide range of influenza viruses, including a Type B strain. Both results modify conclusions suggested by conventional assay methods. Since the LDA experiments seem to be relatively resistant to regulatory interactions which can influence the outcome of standard assay cultures, they can supply information about the characteristics of the pHTL itself that would otherwise be difficult to obtain. PMID- 6242864 TI - [Lactobacillus in the digestive tract and food of long-lived persons in Abkhazia]. PMID- 6242865 TI - [Early adenovirus proteins]. PMID- 6242866 TI - Acupuncture of Yanglao (S.I. 6) point in the treatment of lumbar pain. PMID- 6242867 TI - A morphological study on the receptors of acupuncture points. PMID- 6242868 TI - The lambda and P22 phage repressors. AB - The lambda cI repressor and the P22 c2 repressor contain two structural domains. In both proteins, the N-terminal domains mediate operator recognition and positive control of transcription, and the C-terminal domains mediate subunit oligomerization and recognition of the recA protein. In some cases, structural, biochemical, and genetic studies implicate particular repressor side chains in these processes. PMID- 6242869 TI - Stability distribution in the phage lambda-DNA double helix: a correlation between physical and genetic structure. AB - Statistical analyses on the positional correlation of physical-stability and base sequence distribution maps with genetic map are made for the whole DNA (48502 bases) of lambda-phage. The susceptibility to a double-helix unfolding perturbation and the fraction of the transient opening of a particular region of the double helix are adopted to define this physical stability. The principal features obtained are: A) The DNA double strand of protein coding regions is found to have homostabilizing propensity around a defined stability which is characteristic to each individual gene. B) The stability of the double helix in non-protein coding region fluctuates, on average over the whole region, more than that in protein coding region. C) Boundary regions of protein coding and non protein coding regions are regions of high stability-fluctuation. Stability especially fluctuates at the protein-coding-region side of the boundary. Contrary to the quiet feature of the interior part of protein coding region rather noisy part exists at its edge. D) One frequently opening region coincides with the attaching site for the site specific recombination between phage and bacterial DNA. There are two possible ways to explain the noisy feature in the stability distribution in non-protein coding regions: 1) The region has been used as the locus of recombination as evolution took place. Thus DNAs which were homostabilized around a different value characteristic to each individual DNA, have been joined there many times, so that the noise has accumulated as a remnant of evolutional history; and/or 2) the base-composition homogenizing or double helix homostabilizing mechanism does not work in unneeded region such as non protein coding region or introns. Since corresponding characteristics have been found in our previous analyses on other viral and globin-gene DNAs, the rules mentioned above may be comprehensively extended to other DNAs. PMID- 6242870 TI - [Analysis of speech disorders in handicapped children and adolescents]. PMID- 6242871 TI - Studies of murine lymphocyte alloantigens Ly-7.2. AB - The Ly-7.2 alloantigen has previously been defined by an alloantiserum and shown to be expressed on T and B cells; it is now studied for its distribution on responder and stimulator cells in the mixed lymphocyte reaction, on cells responding to mitogens and on mitogen-induced blast cells. In the mixed lymphocyte reaction, the responder cells were Ly-7.2+; stimulator cells were Ly 7.2-. The Ly-7.2 antigen also had an unusual distribution on cells responding to mitogens: leucoagglutinin-responsive cells were Ly-7.2-, concanavalin A Ly-7.2+, pokeweed mitogen Ly-7.2+/-, and lipopolysaccharide Ly-7.2-, i.e., Ly-7 can distinguish between subpopulations of T cells which respond to mitogens (phytohaemagglutinin and concanavalin A). Ly-7.2 was present on approximately 60% of blast cells induced by all mitogens indicating that both Ly-7.2+ and Ly-7.2- cells could be activated to become Ly-7.2+. Further characterization of concanavalin A and leucoagglutinin-stimulated Ly-7.2+ and Ly-7.2- T blast cells with anti-Ly-2.1 and anti-Ia. 17 monoclonal antibodies demonstrated the presence of several T lymphocyte subsets as both Ly-7+ and Ly-7- blast cells contained Ly 2+, Ly-2-, Ia+ and Ia- cells. Ly-7.2 therefore has a heterogenous distribution on normal and activated T and B cell subpopulations, and is a potentially important antigenic marker for studies of lymphocyte differentiation and function. PMID- 6242873 TI - Access to care on wheels. PMID- 6242872 TI - Opening the door to dental care in Chicago. PMID- 6242874 TI - Sit-down four-handed dentistry: a response to Resolution 38. PMID- 6242876 TI - Sedation and general anesthesia in periodontal surgery. PMID- 6242875 TI - Oral contraceptives and periodontal health. PMID- 6242877 TI - Siderophores of bacteria and fungi. AB - Siderophore-mediated iron assimilation systems are widely distributed in bacteria and fungi. The systems are comprised of low molecular weight ferric-ion specific ligands (siderophores) and cognate cell-bound receptor and utilization components. Most siderophores are classed chemically as hydroxamic acids or catechols; expression of both types is regulated by iron. Of the various siderophore systems present in E. coli, the enterobactin and aerobactin genes, encoded on the chromosome and pColV respectively, have been the most intensively studied to date as regards their molecular genetics. PMID- 6242878 TI - Leprosy vaccine. PMID- 6242879 TI - A clinical case history. Papillon-Lefevre disease. PMID- 6242880 TI - Pre- and postnatal development and ageing of the heart. Ultrastructural results and quantitative data. PMID- 6242881 TI - A new human T-cell differentiation antigen: unexpected expression on chronic lymphocytic leukemia cells. AB - Monoclonal antibody 10.2 reacts with a monomorphic antigen expressed on the surface of virtually all thymocytes, as well as thymus-dependent lymphocytes in the peripheral blood and bone marrow. In contrast, antibody 10.2 did not react with normal peripheral blood B cells, monocytes, or the non-T-cell fraction of bone marrow. This complement fixing IgG2a antibody also reacted with established leukemic T-cell lines, but not with cell lines of either normal or malignant B cell origin. Similarly, when tested against acute leukemia blasts, the 10.2 antibody reacted with those from patients with T-cell acute leukemia, but not with those from patients with acute null cell or non-lymphocytic leukemia. An unexpected exception to this pattern was the reaction of 10.2 antibody with leukemic cells from patients with B-cell type chronic lymphocytic leukemia. Immune precipitates formed with 10.2 antibody and detergent lysates of radiolabeled T-cells contained three polypeptides with molecular weights of 65 000, 55 000, and 50 000 daltons. It has not been determined whether all three of these polypeptides contain the 10.2 antigenic determinant, or whether these proteins represent a multimeric antigen complex. PMID- 6242882 TI - Ly-m11: the H-3 region of mouse chromosome 2 controls a new surface alloantigen. AB - Spleen cells from an SJL mouse immunized with B10.S spleen cells were fused with the nonsecretor myeloma line NS.1. One established hybrid cell line continuously secreted antibody that recognized a new antigenic specificity, tentatively called "Ly-m11." This newly found antigen is detectable on nearly 100 percent of spleen and lymph-node cells, 70 percent of bone-marrow cells, and 20 percent of thymus cells by direct cytotoxicity assays, and on the cells derived from kidney and liver. Strains that are Ly-m11 (+) include C57BL/6, C57BL/10J, B10.S, C57BR/cdJ, C57L/J, and C57BL/KsJ. Other mouse strains so far tested are Ly-m11 (-). The strain distribution pattern distinguished Ly-m11 from any known murine lymphocyte alloantigens, but it follows the H-3 alpha haplotype which is defined by skin transplantation. Linkage tests of nine congenic strains of H-3 and/or H-13/alpha loci and five recombinant inbred lines including CXB, BXH, AKXL, SWXL, and BXD revealed no recombinations between H-3 and Ly-m11 loci on chromosome 2. This newly discovered Ly-m11 alloantigen could itself constitute a minor histocompatibility antigen detectable by serological means. PMID- 6242883 TI - Genetic definition of a further gene region and identification of at least three different histocompatibility genes in the rat major histocompatibility system. AB - Two new recombinant haplotypes of the rat major histocompatibility system, RT1, have been detected in [LEW.1A (RT1a) x LEW.1W (RT1U)] x LEW.1N(RT1n) segregating hybrids. Recombinant r3 carries the RT1.A region (determining classical transplantation antigens) and the RT1.B region (determining strong mixed lymphocyte reactivity and genetic control of antipolypeptide immune responsiveness) of the RT1a parent, bur rejects RT1a skin grafts. Recombinant r4 carries the A and B regions of the RT1u parent, but rejects RT1u skin grafts. The two histocompatibility genes detected are allelic to each other. The relevant locus, designated as H-C, maps to the B-region side of the RT1 system and appears to mark a third RT1 gene region, RT1.C. Availability of haplotypes r3 and r4 allowed the definition of a histocompatibility locus in the B region, H-B. The products of H-C, H-B and of the previously described H-A gene vary in antigenic strength. PMID- 6242884 TI - H-2-controlled polymorphism of the gamma chain of Slp (sex-limited protein). AB - A genetic polymorphism detected by the O'Farrell two-dimensional technique (isoelectric focusing and SDS-PAGE) of the murine sex-limited protein (Slp) is described and shown to map to the H-2 complex. The Slp charge variation was found to be in the gamma chains. Inbred strains carrying the H-2w7 and H-2wr7 haplotypes, which are derived from a wild mouse, had Slp-gamma chains with pI = 6.55 (Slp-1b). All other inbred strains, bearing H-2j,H-2s,H-2p,H-2d,H-2u, as well as three additional Slp-constitutive wild females captured in Chile, had Slp gamma chain with pI = 6.71 (Slp-1a). PMID- 6242885 TI - Identification and genetics of horse lymphocyte alloantigens. AB - Six hundred horses were tested with lymphocytotoxic antisera derived from 550 parous mares and 58 antisera produced by alloimmunization with horse blood cells. Seven equine lymphocyte specificities were identified using correlation analysis of the test data, absorption analysis and lysostripping. These specificities are expressed on lymphocytes and platelets, but not on red blood cells (RBC). Therefore, these specificities do not appear to be products of any of the eight known blood group systems of the horse. The distribution of these specificities in 113 Thoroughbred horses and 57 Arabian horses is presented. Two specificities are subtypic to two other specificities reported here. Family studies indicated that all of these specificities are products of one genetic system. However, it is not clear whether the system consists of one or more loci. PMID- 6242886 TI - Restimulation properties of human alloreactive cloned T-cell lines. Dissection of HLA-D-region alleles in population studies and in family segregation analysis. AB - Alloactivated human lymphocytes were cloned by limiting dilution. After 1 month in culture with T-cell growth factor several clones incorporated tritiated thymidine when stimulated with the appropriate allogeneic cells. Specificity of restimulation of two primed lymphocyte clones, designated 12-2 and 12-8, was studied in detail after varying periods of culture (up to 50 days). Clone 12-2 cells were stimulated only by cells expressing the HLA-Dw antigens of the original priming cells (Dw3); furthermore, this primed lymphocyte reagent specifically recognized antigens associated with only one of the three distinct Dw3-bearing haplotypes from an informative family (KOH). Clone 12-8 cells, on the other hand, failed to recognize Dw3 antigens in the random panel or on homozygous typing cells (including the original priming cell), but were strongly restimulated by certain cells expressing Dw4 antigens. In addition, within family KOH, these restimulating products segregated with another one of the three Dw3 bearing haplotypes but with none of the three Dw4-bearing haplotypes. These two clones exemplify a hitherto unknown precision in cellular typing of the HLA-D region. Clone 12-2 allows the discrimination of a probably rare and as yet undetected HLA-Dw3 subtypic specificity. Clone 12-8, on the other hand, apparently identifies an allelic system segregating with HLA but distinct from the HLA-D determinants definable by HTC-typing. PMID- 6242887 TI - Retention of specific proliferative capacity of cloned human T cells alloactivated against HLA-D alleles. PMID- 6242888 TI - Rat kappa-chain allotypes. III. Serological and genetic analysis of RI-1b cross reactivity in Australian Rattus. AB - The presence of rat kappa-chain allotype specificities (RI-1a and b) has been studied in 13 subspecies of the seven native Australian species of Rattus. RI-1a reactivity was not detected among these rats. On the other hand, extensive cross reactivity was seen with RI-1b, some sera cross-reacting totally (R. leucopus cooktownensis), some not at all (R. colletti), and the remainder showing at least two distinct levels of partial cross-reactivity, confirming the existence of multiple specificities for RI-1b. Three subspecies show polymorphism with respect to RI-1b cross-reactivity (R. sordidus, R. colletti, and R. l. leucopus) and in one case (leucopus) breeding studies have indicated that there is allelic inheritance of this trait. The segregation of RI-1b reactivity has been studied in crosses and backcrosses made between species differing in their RI-1b reactivity, and the results are consistent with the existence of codominant alleles at a single locus. The fact that these species differ extensively in their karyotype opens the door to possible chromosomal localization of this and other genetic traits. PMID- 6242889 TI - Expression of the I-E target antigen for T-cell killing requires two genes. AB - The H-2Ik region encodes at least two different target antigens for unrestricted T-cell mediated killing. The first is controlled by the I-A region alone and the second depends on a pair of alleles, one located to the left of I-B (presumably in I-A) and the other to the right of I-J (presumably in I-E). Hence, effector cells nominally specific for a product of the I-E region do not kill target cells with the same I-E region as the stimulator unless the I-A region is also shared. Some effectors specific for H-2Ik, such as A.TH anti-A.TL and B10.A(4R) anti B10.A(2R), cross-react with B10.A(3R) and B10.A(5R) target cells. A product of the H-2b haplotype was shown to complement products of the H-2d or H-2k haplotypes in forming this cross-reactive determinant. The results are consistent with recent biochemical data on the component chains of Ia antigens. PMID- 6242890 TI - Serological detection of H-2K- and H-2D-gene products. I. Principal difference between T and B lymphocytes in expression of H-2D-encoded alloantigens. AB - Using the fluorescence-activated cell sorter (FACS II), we have analyzed the expression of H-2K- and H-2D-gene products on the membrane of various cellular components of the murine immune system. Using this serological technique we show a basic difference between T and B lymphocytes. Whereas all cellular components analyzed--hydrocortisone-resistant thymocytes, splenic T and B lymphocytes, macrophages and bone-marrow cells--expressed H-2K-subregion-encoded alloantigens at a high density, it seems that the high density expression of H-2D-encoded alloantigens is restricted mainly to B cells and to macrophages. Hydrocortisone resistant thymocytes, splenic T lymphocytes and bone-marrow cells, on the other hand, showed significant expression of the H-2D alloantigens only at low membrane density. These results, then, provide evidence for the existence of an imbalance in serologically detectable expression of H-2K- and H-2D-region-gene products on the cell membrane of various cells comprising the murine immune system. PMID- 6242891 TI - Interaction of H-2Db with mutant histocompatibility gene H (KH-11) in the mouse. AB - The detectable presence of H (KH-11)b, a mutant non-H-2 histocompatibility gene, was previously shown to depend upon the simultaneous presence, in the skin-graft donor, of both the mutant gene and the H-2b haplotype. The experiments reported here demonstrate that H-2Db is the essential element of H-2b for this interaction. Of two H-2Db histocompatibility mutations, H-2bm13 can replace H-2Db in this interaction, but H-2bm14 cannot. PMID- 6242892 TI - Expression of major histocompatibility antigens on human thymocytes studied using monoclonal antibodies. PMID- 6242894 TI - [The morphological study of blood stains]. PMID- 6242895 TI - The role of the pathologist in homicide investigation. PMID- 6242893 TI - Dimethonium, a divalent cation that exerts only a screening effect on the electrostatic potential adjacent to negatively charged phospholipid bilayer membranes. AB - Calcium and other alkaline earth cations change the electrostatic potential adjacent to negatively charged bilayer membranes both by accumulating in the aqueous diffuse double layer adjacent to the membrane and by adsorbing to the phospholipids. The effects of these cations on the electrostatic potential are described adequately by the Gouy-Chapman-Stern theory. We report the results of experiments with ethane-bis-trimethylammonium, a cation that has been termed "dimethonium" or "ethamethonium" in analogy with hexamethonium (hexane-1,6-bis trimethylammonium) and decamethonium (decane-1,10-bis-trimethylammonium). We examined the effect of dimethonium on the zeta potential of multilamellar vesicles formed from the negative lipid phosphatidylserine (PS) and from 5:1 phosphatidylcholine/phosphatidylserine mixtures in solutions containing 0.1, 0.01 and 0.001 M sodium, cesium, or tetramethylammonium chloride. We also examined the effect of dimethonium on the conductance of planar PS bilayer membranes and the 31P NMR signal from sonicated PS vesicles formed in 0.1 M NaCl. We found no evidence that dimethonium adsorbs specifically to bilayer membranes. All the results, except for those obtained with vesicles of low charge density formed in a solution with a high salt concentration, are consistent with the predictions of the Gouy-Chapman theory. We conclude that dimethonium, which does not have the pharmacological effects of hexamethonium and decamethonium, is a useful divalent cation for physiologists interested in investigating electrostatic potentials adjacent to biological membranes. PMID- 6242896 TI - The role of the pathologist in homicide investigation. Reply for Great Britain. PMID- 6242897 TI - The toxicology of fire deaths. PMID- 6242899 TI - The use of the computer in response to disaster. PMID- 6242898 TI - The role of universities in police training. PMID- 6242900 TI - Lightning deaths in Singapore. PMID- 6242901 TI - Detecting bloodstains by microphotometry. PMID- 6242903 TI - Regional organisations in forensic medicine and sciences: an essential for communication. PMID- 6242902 TI - Computer-aided skull-face superimposition by analytical procedures. PMID- 6242904 TI - Sudden cardiac death. A post mortem study. Part II. Myocardial infarction with and without coronary artery pathology. PMID- 6242905 TI - Intoxications mortelles de "sniffers" par des solvants volatils: identification par chromatographie en phase gazeuse couplee a la spectrometrie infra-rouge par transformee de Fourier [Fatal poisonings in sniffers of volatile solvents: identification by gas-phase chromatography coupled to infrared spectrometry with a Fourier transform]. PMID- 6242906 TI - Violence in the Greek family. Past and present. PMID- 6242907 TI - Study of cathepsin A and D activities and Ca, Mg, Cu, Zn, Fe, Na and K levels in pig skin as a tool for the differential diagnosis between vital and postmortem skin wounds. PMID- 6242908 TI - Possible false confessions. PMID- 6242909 TI - The dating of pulmonary emboli. PMID- 6242910 TI - Features of forensic fiction--fact or fantasy. PMID- 6242911 TI - Study of free fatty acids pericardial fluid behaviour in relation to different causes of death. PMID- 6242912 TI - A physician's death presumably related to torture. Difficulties of medico-legal expertise. PMID- 6242913 TI - Aminopeptidase and cathepsin A activity in vitreous humour in relation to causes of death. PMID- 6242914 TI - Medical liability in a large French hospital. A ten years study. PMID- 6242915 TI - Murder by fright. PMID- 6242916 TI - Sudden cardiac death (except coronary diseases). PMID- 6242917 TI - Suicide in a general hospital: medical liability. PMID- 6242919 TI - The cancer patient and his doctor: deontological and psychopathological aspects of the relationship. PMID- 6242918 TI - To be or not to be. PMID- 6242920 TI - Portuguese law and paternity questions. PMID- 6242921 TI - The pathological aspects of the Yorkshire "ripper" case. PMID- 6242922 TI - Death by road traffic accidents. PMID- 6242923 TI - Clinical forensic medicine in the Medico-Legal Institute of Porto. PMID- 6242924 TI - Biochemical timing of wounds in forensic pathology. PMID- 6242926 TI - Human rights and medicine. PMID- 6242925 TI - Kinetics of changes in alpha-esterase levels and their use in differential diagnosis of open skin wounds. PMID- 6242927 TI - The Danish Medico-Legal Council. PMID- 6242928 TI - Approach to the volumetric estimation of the lesions around the path of bullets. PMID- 6242929 TI - Elementary approach to the graphical memorisation of ballistic data. PMID- 6242930 TI - The infrared determination of writing sequence of ball-point pen strokes. PMID- 6242932 TI - The role of the forensic pathologist in the detection of torture. PMID- 6242931 TI - Fatal adverse reactions to drugs. PMID- 6242933 TI - Undergraduate medico-legal education in the United Kingdom. PMID- 6242935 TI - The importance of autopsy in major disasters. PMID- 6242934 TI - The expert witness. The pathologist and his evidence. PMID- 6242936 TI - Rare injury patterns in air plane crashes. PMID- 6242937 TI - Timing of wounds. An introductory review. PMID- 6242938 TI - "The role of the pathologist in homicide investigations". PMID- 6242939 TI - Symposium on the role of the pathologist in homicide investigation. PMID- 6242940 TI - The role of the pathologist in homicide investigation. PMID- 6242941 TI - Morphology of wounds and traffic accident reconstruction. PMID- 6242942 TI - The role of the pathologist in homicide investigation. PMID- 6242943 TI - Symposium on the role of the pathologist in homicide investigation. PMID- 6242944 TI - The role of the pathologist in homicide investigation. PMID- 6242945 TI - Symposium on the role of the pathologist in homicide investigation. PMID- 6242946 TI - Piroxicam: what's new? PMID- 6242947 TI - Pharmacology of collagen. PMID- 6242948 TI - Oxicams--a novel family of non-steroidal anti-inflammatory drugs. PMID- 6242949 TI - A comparison of the pharmacokinetics of piroxicam with those of plain and slow release indomethacin. A crossover study. PMID- 6242950 TI - Comparative steady state pharmacokinetic study of piroxicam and flurbiprofen in normal subjects. PMID- 6242951 TI - The steady-state pharmacokinetics of piroxicam: effect of food and iron. PMID- 6242952 TI - A double blind cross-over comparison of piroxicam and indomethacin in the treatment of rheumatoid arthritis. PMID- 6242953 TI - Comparison of piroxicam with naproxen in rheumatoid arthritis: a double-blind, cross-over, multicentre study. PMID- 6242954 TI - Piroxicam in the treatment of rheumatoid arthritis. PMID- 6242955 TI - A double-blind cross-over comparison of piroxicam mane and piroxicam nocte in osteoarthritis. PMID- 6242956 TI - A double-blind comparison of piroxicam mane with piroxicam nocte in patients awaiting hip and/or knee joint replacement. PMID- 6242957 TI - Piroxicam and naproxen in osteoarthritis: a clinical comparison. PMID- 6242958 TI - A single-blind cross-over comparison of fenbufen 600 mg nocte and piroxicam 20 mg nocte in osteoarthritis. PMID- 6242959 TI - Time of onset and duration of activity of piroxicam in rheumatoid arthritis: a placebo controlled study. PMID- 6242961 TI - Concentrations of tolmetin in plasma and synovial fluid after a single intake in patients with rheumatoid arthritis. PMID- 6242960 TI - Long-term follow-up in the treatment of rheumatoid arthritis with levamisole. PMID- 6242962 TI - The treatment of gout with azapropazone: clinical and experimental studies. PMID- 6242963 TI - Azapropazone--twice or four times daily? PMID- 6242964 TI - Double-blind controlled evaluation of benoxaprofen for treatment of coxarthrosis and gonarthrosis. PMID- 6242965 TI - Persistent dendritic swelling following transient brain ischemia in the rat. PMID- 6242966 TI - Effects of endorphins, enkephalins, certain analogues, and morphine sulfate on brain function and behavior of monkeys: a role in schizophrenia, epilepsy, and analgesia? PMID- 6242967 TI - Sialidosis with partial B-galactosidase deficiency (galactosialidosis). PMID- 6242968 TI - Chemical stimulation to deep forebrain nuclei in parkinsonism and epilepsy. PMID- 6242969 TI - New advances on the regulation of growth hormone (GH) secretion. PMID- 6242970 TI - Teaching neuropsychiatry in New Orleans. PMID- 6242971 TI - Metabolic probes for localization of functional activity in the central nervous system. PMID- 6242972 TI - Stress induced changes in rat hippocampal cholinergic system. PMID- 6242973 TI - Chorea acanthocytosis: clinical pathological and biochemical aspects. PMID- 6242974 TI - Cerebral metabolism with positron emission tomography and 0-15 radiopharmaceuticals. PMID- 6242975 TI - Basal ganglia glucose metabolic and single neural unit activity in experimental hemiplegia. PMID- 6242976 TI - The brain. PMID- 6242977 TI - Changed turnover of monoamines in limbic nuclei in response to stimulation and lesion of the anterior vermal cortex of the cerebellum: studies in cat and rat. PMID- 6242978 TI - Evoked metabolic responses in the limbic-striate system produced by stimulation of anterior thalamic nucleus in man. PMID- 6242979 TI - Idiopathic hypersomnia: a study of 187 personally observed cases. PMID- 6242980 TI - [Periodic hypersomnia--The Kleine-Levin syndrome and its problems. A review of recent cases]. PMID- 6242983 TI - Paradoxical sleep in psychiatric disorders and narcolepsy. PMID- 6242984 TI - The place of sleep disorder centers in the evaluation and treatment of chronic insomniacs. PMID- 6242985 TI - Sleep patterns in extrapyramidal disorders. PMID- 6242986 TI - The circadian rhythm embraces the variability that occurs within 24 hours. PMID- 6242989 TI - Variances in delta activity in patients with brain tumor in each sleep stage-with special reference to computerized topographic display of delta activity and CT scan. PMID- 6242990 TI - International Journal of Neurology is devoted to pathology of the peripheral nerve. PMID- 6242996 TI - Polyneuropathy during perhexiline maleate therapy. PMID- 6242992 TI - Thiamine deficiency neuropathy, a reappraisal. PMID- 6243001 TI - Fine structural investigation of the ontogenetic development of different types of synapses in the nigra an pallidum of the rat. PMID- 6243005 TI - History of neurology in Japan. PMID- 6243011 TI - The initial episode of asthma. PMID- 6243012 TI - When the patient with asthma fails to respond. PMID- 6243013 TI - Adrenergic bronchodilators, old and new. PMID- 6243014 TI - Theophylline therapy. PMID- 6243015 TI - Single-entity sustained theophylline therapy for the pre-school child. PMID- 6243016 TI - Corticosteroids for childhood asthma: systemic and topical treatment. PMID- 6243017 TI - Asthmatic child at home, school, and play: a conference summary. PMID- 6243018 TI - Antidepressants said poisoning threat to children. PMID- 6243019 TI - Toxic-shock syndrome: a case report--I. PMID- 6243020 TI - Toxic-shock syndrome: a case report--II. PMID- 6243021 TI - Herpes simplex, metaherpes: secondary invasive infection of the cornea. PMID- 6243022 TI - Mycoplasma pneumoniae infections. PMID- 6243023 TI - An introduction: contemporary topics in infection control. PMID- 6243024 TI - Infection control series: I. Skin manifestations of selected infectious diseases. PMID- 6243025 TI - Infection control series: II. Total parenteral nutrition and infection. PMID- 6243026 TI - Solitary adult eosinophilic granuloma of bone: report of four cases and review of literature. PMID- 6243027 TI - Infection control series: III. Clinical application of aminoglycoside drug levels. PMID- 6243028 TI - Infection control series: IV. Pneumococcal vaccine in the prevention of pneumonia: establishing an immunization program for patients in hospital. PMID- 6243029 TI - Patient acceptance of an integrated psychiatric/medical unit. PMID- 6243030 TI - Polymyalgia rheumatica and giant cell arteritis. PMID- 6243032 TI - Arnold Klebs and Harvey Cushing at the 1st International Neurological Congress at Berne in 1931. PMID- 6243037 TI - The Erb-Goldflam disease. PMID- 6243040 TI - Clinical statistics of myasthenia gravis in Japan. PMID- 6243043 TI - Central effects of vasopressin in man. PMID- 6243044 TI - Neurophysiological aspects of centrally acting peptides. PMID- 6243048 TI - Medicine and air supremacy. PMID- 6243049 TI - Aeromedical research at Yale. Effects of high altitudes studied in decompression chamber. PMID- 6243050 TI - Developmental anomalies-varience in the expressivity and pattern of affected organs. PMID- 6243051 TI - [The first permanent molar in orthodontics]. PMID- 6243052 TI - [Effect of orkomin on the dynamics of the external respiration function in acute pneumonia]. PMID- 6243054 TI - The role of the academic, voluntary and statutory bodies in the profession--a point of view. PMID- 6243053 TI - Compartmental arthroplasty for gonarthrosis. PMID- 6243055 TI - Eye protection in the dental surgery. PMID- 6243056 TI - Biochemical analysis of various cool drinks with regard to enamel erosion, de- and remineralization. PMID- 6243057 TI - Fruit, fruit juices and dental caries. PMID- 6243058 TI - Implantation cysts as a standardized method of testing root canal cements. PMID- 6243059 TI - [The handling of amalgam]. PMID- 6243060 TI - The palatal ruga pattern in six southern African human populations, part I: A description of the populations and a method for its investigation. PMID- 6243061 TI - [Stable osteosynthesis of unstable per- and subtrochanteric femoral fractures using the 130 degrees double-T plate]. AB - Operative treatment of instable inter- and subtrochanteric fractures with a new 130 degrees-double-T-plate allowed, in spite of high-risk patients (age x=81 to 84 years, multimorbidity 92%), full maximum load by the third day after operation and a shorter time of hospitalization of 22.5 days. Mortality rate came up to 9%. Load experiments showed that the double-T-profiled 130 degrees-plate with increased lateral moment of resistance could support a weight five times greater than that supported by 130 degrees-implants with transversal blades or DHS screws. In addition, the double-T (I-Beam) profiled 130 degrees-angled-plate had a resistance to bending two-and-a-half times greater than the hip compression screw from Pohl and has demonstrated its marked clinical success. Follow-up made in 256 patients for 6 to 66 months after double-T-plate osteosynthesis showed good results in 82.2% of the patients satisfied with the outcome of surgery, 13.9% needed two crutches and found the result achieved poor. Only 3.9% of all patients achieved no walking capability. PMID- 6243062 TI - [Clinico-experimental evaluation on the use of sulprostone, new PGE2 derivative. I. Interruption of pregnancy in the first trimester]. PMID- 6243063 TI - The treatment of fractured enamel adjacent to an amalgam restoration: a case report. PMID- 6243064 TI - Treatment of cleft lip and palate. Part IV: Cleft lip and palate cases, presenting at a late age. PMID- 6243065 TI - Structure-activity studies of aplysiatoxin-type tumor promoters. AB - The cellular activities and responses of aplysiatoxin in vitro and in vivo are very similar to those of the diterpene 12-O-tetradecanoylphorbol-13-acetate (TPA) and the indole aklaloids teleocidin B and lyngbyatoxin A. Even though aplysiatoxin, TPA, and teleocidin B are chemically and structurally quite distinct from one another, all three compounds produce essentially the same plethora of biological effects by apparently binding to the same receptor on the cell membrane, the so-called phorboid receptor. Several aplysiatoxin-type compounds have been studied in three test systems for evaluating potential tumor promoting activity, viz. mouse ear skin for irritation, murine dorsal skin for the induction of ornithine decarboxylase (ODC) activity, and an epidermal particulate fraction of dorsal mouse skin for the inhibition of specific binding of [3H]-TPA. Some of the compounds were tested in a 30-week two-step carcinogenesis experiment in mice. In most cases the results of the 30-week test correlated with the activities of the three preliminary tests. The overall study indicated that the hydroxyl groups on C-3, C-20, and C-30 are essential for maximum activity. Inspection of Dreiding models showed that the oxygens on C-27, C-3, and C-30 of aplysiatoxin are aligned with the oxygens on C-3, C-4, and C-20 of TPA, respectively. The latter oxygens are in functional groups that are known to be necessary for the high activity of TPA. PMID- 6243066 TI - The dental manpower situation in South Africa. PMID- 6243067 TI - Chlamydia trachomatis in Pap smears. PMID- 6243068 TI - [Bad news for tooth restoration. Comment on J. Wurz, M. Johner and O. Pohler's "Tooth rebuilding with nonprecious metal-containing screws and posts" (Schweiz, Mschr. Zahnheilk. 89: 1162, 1979)]. PMID- 6243069 TI - [Radiography in the problem of implantation]. PMID- 6243070 TI - [Clinical evaluation of the biological action of a toothpaste]. PMID- 6243071 TI - The impacted maxillary canine. PMID- 6243072 TI - [Rational antibiotic therapy in dentistry]. PMID- 6243073 TI - The current state and prospects of radiation protection in CSSR. PMID- 6243074 TI - Experiences with bone scanning in differential diagnosis of local bone lesions. AB - Because some primary tumours often metastasize to the skeleton, their early detection is essential for further therapy and prognosis. Radiographic examination is not sufficiently sensitive for early detection of bone metastases, because it can reveal the typical sign of metastases--decalcification--only after loss of 30-50% of the original amount of calcium from bone tissue (18). Bone scanning with bone-seeking radiopharmaceuticals represents a viable technique for early detection of bone lesions, especially early metastatic disease. The indication for this examination is undoubtedly in breast cancer, cancer of prostate, lung, thyroid gland, hypernephroma, melanoma, plasmocytoma and malignant lymphomas. After good clinical experience of the authors with bone scanning in detection of secondary bone tumours in known primary localisations (9, 14, 15, 10), they tried to elaborate in this paper indicative criteria for bone scanning in patients with suspicious secondary tumourous lesions by unknown primary localisations. PMID- 6243075 TI - Phage typing of South Indian M. tuberculosis strains by "surface" and "overlay" method. PMID- 6243076 TI - Bladder evacuating capacity after renal transplantation. AB - Using the radioisotope method, we examined the residual bladder volume in 30 persons without kidney and urinary tract disease, 71 patients with recurrent urinary tract infections and 56 renal transplant patients. The results showed significantly higher bladder volumes in patients with urinary tract infection than in transplant patients without urinary tract infection, non-transplant patients with urinary tract infections and subjects without urinary tract disease. Increased residual bladder volume, which is a manifestation of disturbed bladder evacuating capacity, is not related to age, the length of the postoperative period, the presence of vesicoureteral reflux, or the pretransplantation level of diuresis. The results suggest that the major factor responsible for the disturbed evacuating capacity is the degree of bladder wall injury sustained on neo-ureteral implantation. Functional disturbances render the bladder prone to bacterial invasion of the lower urinary tract and recurrent urinary tract infection. PMID- 6243077 TI - Preprosthetic program for the amputee. PMID- 6243079 TI - [Dental hygiene in orthodontics]. PMID- 6243078 TI - [Retroperitoneal tuberculous abscess]. PMID- 6243080 TI - [Iatrogenic cases of death]. PMID- 6243081 TI - The child under the stress of hospitalization and surgery. PMID- 6243082 TI - The use of membrane vesicles in transport studies. AB - Transport-competent plasma membrane vesicles isolated from mammalian cells provide a system to investigate mechanisms and regulation of nutrient and ion transport systems. The characteristics of membrane vesicle systems to study transport in erythrocytes, renal and epithelial membranes, Ehrlich ascites cells, and mouse fibroblasts are discussed. Studies of Na+-stimulated and Na+ independent amino acid and glucose transport in these systems are evaluated, with emphasis on experimental verification of concepts stated in the Na+ gradient hypothesis. Nucleoside, phosphate, and calcium transport systems in plasma membrane vesicles from mouse fibroblast cultures are discussed. Also, current biochemical approaches to investigate mechanisms of regulation of nutrient transport systems by hormones or cellular proliferative state are described. PMID- 6243083 TI - Physical chemical studies of the structure and function of DNA binding (helix destabilizing) proteins. AB - Binding of proteins to DNA is fundamental to the mechanisms of replication, recombination and gene expression. The specific molecular features of DNA recognized by complementary features of the three-dimensional structure of the DNA binding proteins are under intensive investigation. Two large classes of DNA binding proteins have emerged. One class includes enzymes such as the RNA polymerases and restriction endonucleases and the nonenzymatic repressor proteins which recognize unique sequences present in only one or a few copies per genome. A second group is made up of non-sequence-specific DNA binding proteins which bind to DNA at high density and modulate subsequent enzymatic transformations of the DNA. Among the latter group are those proteins originally termed "unwinding proteins", which have in common a higher affinity for single-stranded than for double-stranded DNA and thus promote the melting of double-stranded DNA. They are better termed helix-destabilizing proteins to distinguish them from the enzymes which "unwind" the helix by making and breaking phosphodiester bonds. Because the helix-destabilizing proteins form complexes with all single-stranded DNA regardless of base sequence, the molecular details of complex formation have been much more accessible to direct physicochemical measurements. Structural conclusions derived with techniques which include chemical modification, ultraviolet spectroscopy, circular dichroism, NMR, and X-ray diffraction will be reviewed. The following proteins will be discussed in detail; the gene 32 protein of bacteriophage T4, the gene 5 protein from bacteriophage fd, and the helix destabilizing protein from E. coli. The largest amount of specific structural information is available for the gene 5 protein and specific models for this protein and its complexes with DNA based on NMR and X-ray diffraction data are presented. A number of other helix-destabilizing proteins from both prokaryotes and eukaryotes have been described and a survey of these will be given. Some of the basic molecular features of DNA-protein interactions emerging from studies of the helix-destabilizing proteins are likely to be shared by the more highly specific binding proteins like the RNA polymerases and repressors. Properties of some of these more complex systems which suggest this will be discussed. PMID- 6243084 TI - Herpes: scourge of the seventies. PMID- 6243085 TI - Identification of type A and type C virus particles in BF murine osteosarcoma. AB - Two types of virus particles, intracisternal type A and extracellular type C with budding, were detected in the same cells of BF osteosarcoma, its cultured cell lines, and their BFO tumors in CBA mice. The type C particles were approximately 100 microns in diameter. The buoyant density of the virions was 1.16g/ml in sucrose and 1.07 g/ml in Ficoll. A 72S RNA was demonstrated by gel electrophoresis, but no DNA was detected. Reverse transcriptase activity was also demonstrated in detergent-treated virions. Thus, the particles seem to be RNA virus. Cellular transformation and focus formation were observed after rat and mouse embryo cell monolayers were infected with the virus. The same kind of osteosarcoma was produced by inoculation of cloned transformed cells (BFOSV) of CBA embryo cells into CBA mice. Thus, the virus seems to be an oncornavirus. PMID- 6243086 TI - Effect of methotrexate on 5-phosphoribosyl 1-pyrophosphate levels in L1210 leukemia cells in vitro. PMID- 6243088 TI - Ott F. E. Muhlbock 1906--1979. PMID- 6243087 TI - Detection of antibodies cross-reactive with type C RNA tumor viral p30 protein in human sera and exudate fluids. AB - Human sera and human exudate fluids were surveyed for the presence of antibodies cross-reacting with a type C viral protein with a molecular weight of 30,000 (p30). Antibodies cross-reactive with type C viral p30 were concentrated by means of affinity chromatography using Sepharose beads to which disrupted Simian sarcoma virus or Rauscher murine leukemia virus p30 had been coupled. Eluates obtained from the affinity beads were tested for activity against Rauscher murine leukemia virus p30, Simian sarcoma virus p30, and endogenous feline virus RD-114 p30 by radioimmunoprecipitation. Of 57 eluates tested, 29 showed activity against type C viral p30. A number of eluates were also tested for anti-p30 activity by a visual microcytotoxicity assay. Of 11 eluates positive in the radioimmunoprecipitation assay, five were also positive in the microcytotoxicity assay. PMID- 6243089 TI - Analysis of transcription during type C viral induction using cell permeabilization techniques. AB - The reversible cell permeabilization procedure of Castellot et al. has been applied to chemical induction of endogenous type C virus from mouse cells. This procedure has provided a direct demonstration of the alpha-amanitin sensitivity of viral transcription in intact cells at concentrations known to inhibit RNA polymerase II. PMID- 6243090 TI - Effects of thioacetamide treatment on nuclear envelope nucleoside triphosphatase activity and transport of RNA from rat liver nuclei. AB - An in vitro system was used for investigating transport of rapidly labeled RNA from liver nuclei isolated from control and thioacetamide-treated rats. An enhanced transport was observed in preparations from thioacetamide-treated animals. Analysis of transport at various temperatures indicated that it proceeded as an energy-requiring process, even in the absence of an exogenously added energy source, and was related to hydrolysis of high-energy nucleoside triphosphate esters. In control preparations, a nucleoside triphosphatase (NTPase) is present in nuclear envelopes, and this TNPase activity appears to be intimately related to in vitro RNA transport. Nuclear membranes were isolated from purified nuclear preparations taken from control and thioacetamide-treated rats and were examined for NPTase activity. The NTPase activity was significantly greater in the preparations from thioacetamide-treated animals. These observations indicate that an early change associated with carcinogen exposure is an enhanced NTPase activity. This may underlie the enhanced RNA transport observed in vitro. PMID- 6243091 TI - Growth of human breast carcinomas in nude mice and subsequent establishment in tissue culture. AB - Thirty-two malignant human breast tumors were implanted s.c. in female nude mice. Seven tumors survived for two passages, and four were established into permanent transplantable tumor lines. The transplantable tumors have retained the histopathology of the original tumor throughout passaging in the nude mice. In addition, two of the transplantable tumors have low concentrations of estrogen receptor. Tissue culture of the original tumor specimens upon receipt resulted in epithelial outgrowth in 15 of 32 primary cultures. However, no permanent cell lines were established. Attempts to culture 23 tumors frozen with dimethyl sulfoxide upon receipt were unsuccessful. In contrast, establishment of cell strains was successful with tumor specimens cultured following passage in the nude mice; three cell strains were initiated from two of the transplantable tumors. PMID- 6243092 TI - Effects of growth hormone and glucagon on ornithine decarboxylase activity and adenosine 3',5'-monophosphate levels in isolated rat hepatocytes. PMID- 6243093 TI - Effects of the calcium ionophore A23187 on dispersed bovine parathyroid cells. PMID- 6243094 TI - Effects of prolactin on testicular regression and recrudescence in the golden hamster. AB - Transfer of adult male hamsters from a long to a short photoperiod causes testicular atrophy, which is accompanied by decreases in testicular LH receptors and in plasma PRL and testosterone levels. A decrease in plasma gonadotropin levels is also frequently observed. When the decline in peripheral PRL concentration is prevented by transplantation of homologous pituitary(ies) under the kidney capsule, testicular atrophy is delayed and incomplete. This appears to be due to the maintenance of testicular LH receptors by PRL secreted from the grafts and probably also to the stimulation of GSH release from the in situ pituitary. In hamsters maintained in a long photoperiod, ectopic pituitary homografts can increase testicular LH receptor levels, concentrations of testosterone and FSH in the plasma, and the weights of the testes and the seminal vesicles. In contrast to the findings obtained in rats and mice, chronic hyperprolactinemia in the male hamster does not inhibit gonadotropin release or interfere with copulatory behavior. These findings are consistent with our earlier suggestion that PRL plays an important part in the regulation of gonadal function in the male hamster but indicate that testicular atrophy in a short photoperiod cannot be explained solely by a reduction in PRL release. PMID- 6243096 TI - Progestin receptors in rat brain: distribution and properties of cytoplasmic progestin-binding sites. AB - Putative progestin receptors have been characterized in brain and pituitary tissue from untreated and estrogen-primed ovariectomized-adrenalectomized rats. The properties of these sites appear indistinguishable from those of cytoplasmic progestin receptors from the uterus: 1) sedimentation coefficient of 7S, which is reduced by half in the presence of 0.3 M KCl; 2) specificity of binding which strongly favors synthetic and natural progestins as opposed to glucocorticoids, androgens, and estrogens; 3) a dissociation constant for binding the synthetic progestin [3H]R5020 (17 alpha, 21-dimethyl-19-norpregna-4, 9-diene-3,20-dione) of 0.3 nM; and 4) similar rates of formation and dissociation of the [3H]R5020 receptor complexes. In these respects, the estrogen-inducible and noninducible receptors of the brain also appear to be indistinguishable from each other. Estrogen induction of progestin receptors is apparent in uterus (6-fold), pituitary (8-fold), mediobasal hypothalamus (4-fold), and preoptic area (4-fold), all estrogen receptor-containing areas. The corticomedial amygdala does not show an estrogen effect on progestin receptor levels even though it contains estrogen receptor sites. The midbrain of the rat doeogen-insensitive receptors in the brain is relatively low and of the same order of magnitude as in nonstimulated hypothalamus, preoptic area, and pituitary, yet variations are seen among the estrogen-insensitive structures, with lowest levels occurring in cerebellum (6-7 fmol/mg protein) and highest levels occuring in cerebral cortex (approximately 25 fmol/mg protein). These findings are discussed in relation to the actions of progesterone which do and do not require estrogen priming and in relation to intracranial progesterone implantation studies. PMID- 6243095 TI - Progestin receptors in the brain and pituitary of the bonnet monkey (Macaca radiata): differences between the monkey and the rat in the distribution of progestin receptors. PMID- 6243097 TI - Comparison of the response characteristics of four lipogenic enzymes to 3,5,3' triiodothyronine administration: evidence for variable degrees of amplification of the nuclear 3,5,3'-triiodothyronine signal. PMID- 6243098 TI - Prolactin regulation of casein gene expression: possible mediators. PMID- 6243099 TI - Epinephrine inhibits thyrotropin-stimulated adenosine 3',5'-monophosphate accumulation in cat thyroid tissue. PMID- 6243100 TI - Studies on the irreversible nature of prolactin binding to receptors. AB - Studies on hormone-receptor interactions generally assume that the formation of a hormone-receptor complex is a reversible process. This assumption has been examined directly in three experiments using liver membrane receptor preparations from pregnant rats and ovine PRL (oPRL). In Exp 1, Receptors were preincubated with a range of concentrations of oPRL at 23 C for periods up to 60 min, washed thereafter to remove free oPRL, and subsequently incubated with [125I]iodo-oPRL (23 C) to determine specific binding. Preincubation of receptors (0.25 mg membrane protein) with oPRL (5 ng) for periods as brief as 10 min reduced subsequent binding of [125I]iodo-oPRL to receptor, suggesting incomplete dissociation of oPRL even after 30 h. In Exp 2 after preincubation for 30 min with oPRL and subsequent incubation with [125I]iodo-oPRL for 19 h, membranes were washed, and the dissociation (23 or 37 C) of [125I]iodo-oPRL from the hormone receptor complex in the presence or absence of 1000 ng oPRL was studied. After 48 h, only 35-50% of the [125I]iodo-oPRL dissociated from the hormone-receptor complex even in the presence or excess oPRL, indicating a heterogeneity of binding sites (i.e. 50-65% irreversible; 35-50% reversible). When pregnant rat serum was used in place of oPRL or when rabbit mammary glands were used instead of rat livers to prepare receptor preparations, results were similar to those described above, except for the nearly complete dissociation (90%) obtained at 37 C using rabbit mammary gland receptors. In Exp 3 after incubation (10 min, 2 h, or 15 h) of rat liver receptors with [125I]iodo-oPRL plus various amounts of oPRL, the hormone-receptor complex could be completely dissociated with 5 M MgCl2, restoring binding affinity and capacity of receptor to their original values. Labeled oPRL dissociated by MgCl2 treatment from such a complex is capable of binding to fresh receptor. These data strongly suggest that the PRL receptor interaction, particularly the rat liver receptor interaction with PRL under usual in vitro conditions, is not reversible to a significant degree. This is not due to hormone or receptor damage but to a significant number of binding sites (50-65%) in the receptor preparation which are not reversible except under extreme conditions. PMID- 6243101 TI - The effect of unit gravity sedimentation on adrenal steroidogenesis by isolated rat glomerulosa and fasciculata cells. PMID- 6243102 TI - The development of steroidogenic capability and responsiveness to gonadotropins in cultured neonatal rat ovaries. PMID- 6243103 TI - Facilitatory actions of guanidine on synaptic transmission in mammalian brain slices. PMID- 6243104 TI - K+ and Na+ activation of cerebellar 5'-nucleotidase. PMID- 6243105 TI - Entamoeba histolytica: nucleic acid precursors affecting axenic growth. PMID- 6243106 TI - Entamoeba histolytica: isolation of ferredoxin. PMID- 6243107 TI - An enzymatic alteration secondary to adenylyl cyclase deficiency in the cr-1 (crisp) mutant of Neurospora crassa: nicotinamide adenine dinucleotide (phosphate) glycohydrolase overproduction. PMID- 6243108 TI - Saturation kinetics applied to in vitro effects of low prostaglandin E2 and F 2 alpha concentrations on ion transport across human jejunal mucosa. PMID- 6243109 TI - Hepatitis A and B virus markers in immune serum globulin. PMID- 6243110 TI - Comparison of methionine-enkephalin and morphine in the stimulation of gastric acid secretion in the dog. AB - In dogs with Heidenhain pouches and gastric fistulas, we studied acid secretion in response to systemic or portal infusion of methionine-enkephalin (met enkephalin), enkephalin-analog, or morphine. All these opiate compounds caused a dose-dependent increase in acid secretion under basal conditions and resulted in a significant rise in pentagastrin- or histamine-induced acid secretion. The stimulation by opiates of gastric secretion was accompanied by an increase in the mucosal blood flow but without any significant change in serum gastrin concentration. Gastric acid stimulation by met-enkephalin and morphine was strongly inhibited not only by naloxone, an opiate antagonist, but also by blockers of H2-receptors (metiamide) or cholinergic receptors (atropine), suggesting a cooperative interaction between opiates and other stimuli of parietal cells. The gastric stimulation by met-enkephalin and its analog, but not by morphine, was markedly reduced by portal administration of these compounds, indicating a marked inactivation of opiate peptides by hepatic transit. This study shows that enkephalin and morphine stimulate gastric acid secretion by a gastrin-independent mechanism sensitive to atropine and H2-blocker and probably involving opiate receptors. PMID- 6243112 TI - Endogenous opiates and gastric acid secretion. PMID- 6243111 TI - Studies on gastrin secretion in vitro from cultures of rat pyloric antrum: effects of agents modifying the microtubular-microfilament system. AB - The purpose of the present study was to examine the effects of microtubular microfilament (MT-MF) modifying agents on gastrin release from antral mucosal cells maintained for 3 days under tissue culture conditions. Gastrin levels in the media, determined by radioimmunoassay, were monitored at hourly intervals for 6-8-hr periods. Colchicine, 1 mM, produced mild depression in media gastrin levels and completely inhibited dcAMP-theophylline-induced gastrin release. Ethyl alcohol depressed secretion of gastrin. Conversely, colchicine at 0.01 mM, significantly increased levels of gastrin. Gastrin levels were also significantly increased by tetracaine, 1 mM, and by deuterium oxide, 75% and 37.5%. Cytochalasin D had little effect on resting gastrin levels. Results of these experiments indicate response of gastrin-producing cells maintained under these conditions to a number of test agents; that the secretory responses of gastrin cells to the MT-MF modifying agents are similar to those of other endocrine cells in which concommitant changes in the MT-MF system have been studied, providing support for the proposal that this system is involved in the sequence of intracellular events which leads to gastrin secretion. PMID- 6243113 TI - Conflicts and frustration influencing nurses from other countries. PMID- 6243114 TI - Problems foreign nurses encounter in passing psychiatric nursing on U.S. exams for licensure. PMID- 6243115 TI - Trends in general and psychiatric nursing education in selected foreign countries. PMID- 6243116 TI - Taxonomy for development of perceptual skills. PMID- 6243117 TI - The issue of change: its relationship to teaching foreign nurse students. PMID- 6243118 TI - Preparing women's health care nurse practitioners. PMID- 6243119 TI - Group process-success in one graduate nursing program. PMID- 6243120 TI - A nursing clinic: the challenge for student learning opportunities. PMID- 6243121 TI - The problem of communication in a summer workshop for foreign nurses. PMID- 6243123 TI - Identification of DNA sequence changes leading to loss of transforming ability in polyoma virus. PMID- 6243122 TI - Modulation of somatostatin receptors by thyrotropin-releasing hormone in a clonal pituitary cell strain. PMID- 6243124 TI - Partial purification and characterization of reticulocyte phosphatase with activity for phosphorylated peptide initiation factor 2. AB - An enzyme fraction containing phosphatase activity for phosphorylated eukaryotic peptide initiation factor 2 (eIF-2) has been isolated from rabbit reticulocytes and partially characterized. The enzyme efficiently catalyzes release of phosphate from the small subunit of eIF-2 (eIF-2 alpha) that has been phosphorylated by the hemin-controlled repressor. It is shown to restore activity of this phosphorylated eIF-2 for binding of methionyl-tRNAf to 40 S ribosomal subunits in a partial reaction of peptide initiation. The enzyme fraction also has phosphatase activity for eIF-2 phosphorylated in its largest subunit and for the 100,000-dalton peptide associated with the eIF-2 alpha kinase activity of the hemin-controlled repressor. The phosphoprotein phosphatase has been isolated by a procedure involving precipitation with ethanol at room temperature and has an apparent molecular weight in the order of 76,000. Its phosphatase activity for eIF-2 alpha is stimulated about 3-fold by optimal concentrations of Mn2+, but is not stimulated by Ca2+ or Mg2+. The enzyme is strongly inhibited by Fe2+ and by purine nucleoside diphosphates. PMID- 6243125 TI - Inhibition of pyridoxal kinase by the pyridoxal-gamma-aminobutyrate imine. PMID- 6243126 TI - Surface structure changes of rat adipocytes during lipolysis stimulated by various lipolytic agents. A scanning electron microscopic study. AB - A qualitative and quantitative electron microscopic study was performed on rat adipocytes during stimulation of lipolysis by various agents. Scanning electron microscopy of control cells revealed a spherical cell with a textured glycocalyx surface exhibiting small irregular projections. Globular surface evaginations or protrusions measuring 8-18 muM in diameter were seen on cell hemispheres, and there was an average of one protrusion for every two hemispheres examined. Distribution analysis showed that 60 percent of the hemispheres had no protrusions, and 25, 10, and 5 percent of the hemispheres had one, two or three protrusions, respectively. Thin-section and freeze- fracture electron microscopy of the protrusions showed a small triglyceride droplet surrounded by a thin cytoplasmic rim that was continuous with the main cytoplasmic matrix. The glycocalyx coating and plasma membrane extended from the cell surface onto, and over, the protrusion. Scanning microscopy of cells stimulated by lipolytic agents, including epinephrine, adrenocorticotropic hormone, theophylline, and dibutyryl cyclic AMP, revealed a dose-dependent increase in the number of protrusions per cell hemisphere. Maximal concentrations of lipolytic hormones cuase an average 2.5-fold increase in the number of protrusions per hemisphere without changing the average size of the protrusions. Only 40 percent of the stimulated cell hemispheres exhibited no protrusions; over 15 percent of the cells contained three or more; and a number of the protrusions were multilobulate. Insulin prevented the increase in the number of protrusions and the change in distribution caused by the lipolytic hormones but did not prevent the increase caused by theophylline and dibutryl cyclic AMP. The data suggest that the protrusions are a structural feature of the cell and may be related to the lypolytic pathway. These observations may help explain some of the discrepant biochemical data relating to hormonal stimulation of lipolysis. PMID- 6243127 TI - Adrenocorticotropin deficiency: correction of hyponatremia and hypoaldosteronism with chronic glucocorticoid therapy. AB - A 36-yr-old woman with a chronic wasting illness associated with hyponatremia and hypotension proved to have secondary adrenal insufficiency and low levels of GH and PRL. TSH, LH, and FSH responses remained normal. Aldosterone excretion was markedly reduced (0.74 microgram/day) before replacement therapy was started, but normal renin and aldosterone responses to sodium restriction were observed after 6 months of corticosteroid treatment. These responses were maintained after acute steroid withdrawal despite the continued absence of ACTH. Chronically adequate glucocorticoid levels were necessary to maintain a normal aldosterone response in this patient. If there is also a pituitary factor required for this response, it does not appear to be ACTH. PMID- 6243128 TI - Estriol-3-glucuronide and estriol-16-glucuronide in amniotic fluid during normal pregnancy. PMID- 6243129 TI - Lack of response of serum somatomedin to hyperprolactinemia in humans. AB - Because animal experiments have suggested that PRL might regulate the serum somatomedin (SM) concentration, the effect of sustained hyperprolactinemia on the serum SM level was studied in patients with proven pituitary microadenomas. PRL was determined by RIA. SM was measured on the same sample by a human placental membrane radioreceptor assay in which all SMs cross-react. The mean serum SM (+/ SE) in 16 females with elevated PRL levels from 68--21,000 ng/ml was 0.97 +/- 0.08 U/ml. This was not statistically different from that of 29 normal women, (P greater than 0.2). The mean SM for the 3 male patients with serum PRL levels from 570--5,050 ng/ml was in the lower range for normal males. There was no correlation in either group between the serum SM and PRL levels. These results indicate that PRL is not a major regulator of the serum SM concentration in man. PMID- 6243130 TI - Plasma beta-endorphin responses to somatostatin, thyrotropin-releasing hormone, or vasopressin in Nelson's syndrome. AB - To elucidate the regulation of secretion of beta-endorphin in Nelson's syndrome, both ACTH and beta-endorphin were measured using RIA. We found that beta endorphin and ACTH were secreted concomitantly in responses to the administration of lysine-8-vasopressin and TRH. Conversely, the administration of somatostatin to this patient reduced the secretion of both beta-endorphin and ACTH. Thus, beta endorphin is probably secreted cooredinately with ACTH in patients with Nelson's syndrome. PMID- 6243131 TI - Beta-Adrenergic receptors and catecholamine-sensitive adenylate cyclase of the human placenta. AB - Beta-Adrnergic receptor and beta-adrenergic sensitive adenylate cyclase were demonstrated in membrane fractions of human placenta. Placental membranes from normal term pregnancies bound the beta-adrenergic antagonist ( )[3H]dihydroalprenolol to a single saturable class of sites (Kd = 2.31 +/- 0.23 nM; n = 9; maximal capacity, 112 +/- 9 fmol/mg). Competition for binding was stereoselective for (-)isomers of propranolol, and beta-adrenergic agonists displayed competition for the placental receptor in the order (-)isoproterenol greater than (-)epinephrine greater than (-)norepinephrine, typical of a beta 2 type receptor. Beta-Adrenergic receptor was present in placental tissue as early as 10 weeks gestational age, and binding capacity decreased slightly with advancing gestation. [3H]Dihydroalprenolol binding was coupled to epinephrine stimulated adenylate cyclase activity throughout gestation. The subcellular distribution of both beta-adrenergic receptors and epinephrine-stimulated adenylate cyclase suggest their localization primarily in nonbrush border membrane fractions, presumably from plasma membranes more closely related to the fetal rather than to the maternal circulation. Epinephrine-sensitive adenylate cyclase was not present in purified brush border preparations which were directly exposed to maternal blood in the intervillous space. PMID- 6243132 TI - Latent ability to produce human chorionic gonadotropin in response to dibutyryl adenosine 3',5'-monophosphate in the BeWo-NBC trophoblastic cell line. PMID- 6243133 TI - Pregnancy-specific beta-1-glycoprotein in trophoblastic disease. PMID- 6243134 TI - Modulation of homologous receptor concentrations: a sensitive radioassay for human growth hormone in acromegalic, newborn, and stimulated plasma. PMID- 6243135 TI - Decreased adrenal responsiveness in hypothermic patients. AB - We have performed ACTH simulation tests in a total of 14 subjects who were hypothermic at the time of initial presentation. Plasma cortisol values were measured before and 1 h after an iv dose of 25 U synthetic ACTH. The cortisol response was depressed in these subjects, with a mean rise of 32% and an absolute mean rise of 5.0 microgra/dl. There appeared to be a temperature threshold effect, with only minimal responses observed below 32 C. A subgroup of 5 patients with sluggish responses to ACTH while hypothermic (mean cortisol rise, 12.5%) were retested after warming and responded normally (mean rise, 166%). Thus, ACTH stimulation tests may be misleading in the hypothermic patient and should be performed only after body temperature has returned to normal. PMID- 6243136 TI - Alpha-Subunit in sera of choriocarcinoma patients in remission. PMID- 6243137 TI - Variant human phosphoribosylpyrophosphate synthetase altered in regulatory and catalytic functions. AB - An inherited, structurally abnormal and superactive form of the enzyme 5 phosphoribosyl 1-pyrophosphate (PP-ribose-P) synthetase (EC 2.7.6.1) has been characterized in fibroblasts cultured from a 14-yr-old male (S.M.) with clinical manifestations of uric acid overproduction present since infancy. PP-ribose-P synthetase from the cells of this child showed four- to fivefold greater than normal resistance to purine nucleotide (ADP and GDP) feedback inhibition of enzyme activity and hyperbolic rather than sigmoidal inorganic phosphate (Pi) activation in incompletely dialyzed extracts. Excessive maximal velocity of the enzyme reaction catalyzed by the mutant enzyme was indicated by: enzyme activities twice those of normal at all concentrations of Pi in chromatographed fibroblast extracts; normal affinity constants for substrates and for the activator, Mg2+; and twofold greater than normal activity per immunoreactive enzyme molecule. The mutant enzyme thus possessed deficient regulatory and superactive catalytic properties, two mechanisms previously demonstrated individually to underlie the excessive PPRribose-P and uric acid synthesis of affected members of families with superactive PP-ribose-P synthetases. Increased PP-ribose-P concentration (4-fold) and generation (2.7-fold) and enhanced rates of PP-ribose-P dependent purine synthetic reactions, including purine synthesis de novo, in S.M. fibroblasts confirmed the functional significance of this patient's mutant enzyme. Diminished stability of the variant PP-ribose-P synthetase was manifested in vitro by increased thermal lability and in vivo by deficiency of enzyme activity at Pi concentrations greater than 0.3 mM in hemolysates and by an accelerated, age-related decrement in enzyme activity in lysates of erythrocytes separated by specific density. Despite the diminished amount of PP-ribose-P synthetase in the S.M. erythrocyte population, S.M. erythrocytes had increased PP-ribose-P concentration and increased rates of incorporation of [14C]adenine and hypoxanthine into acid-soluble nucleotides during incubation at 1 mM Pi. These findings provided further confirmation of the extent to which PP-ribose-P synthesis is modulated in the normal cell at physiological Pi concentration by purine nucleotide inhibition of PP-ribose-P synthetase. The activity and kinetic characteristics of PP-ribose-P synthetase from fibroblasts of the mother of patient S.M. indicated that this woman was a heterozygous carrier of the enzyme defect expressed in hemizygous manner by her son. PMID- 6243138 TI - Alpha adrenergic contributions to dysrhythmia during myocardial ischemia and reperfusion in cats. AB - Alpha compared to beta adrenergic contributions to dysrhythmias induced by left anterior descending coronary occlusion and by reperfusion were assessed in chloralose-anesthetized cats (n = 96). Alpha receptor blockade with either phentolamine or prazosin significantly reduced the number of premature ventricular complexes during coronary reperfusion (321 +/- 62-14 +/- 10 premature ventricular complexes, P less than 0.001), abolished early ventricular fibrillation (from 25% in controls to 0%), and prevented the increase in idioventricular rate seen with coronary reperfusion. However, beta-receptor blockade was without effect. Ventricular dysrhythmias induced by coronary occlusion alone (without reperfusion) were attenuated markedly by alpha-receptor blockade under conditions in which perfusion (measured with radiolabeled microspheres) within ischemic zones was not affected. Alternative sympatholytic interventions including pretreatment with 6-hydroxydopamine to deplete myocardial norepinephrine from 8.8 +/- 1.4 to 0.83 +/- 0.2 ng/mg protein and render the heart unresponsive to tyramine (120 microgram/kg) attenuated dysrhythmias induced by both coronary occlusion and reperfusion in a fashion identical to that seen with alpha-receptor blockade. Although efferent sympathetic activation induced by left stellate nerve stimulation increased idioventricular rate from 66 +/- 6 to 144+/- 7 beats/min (P less than 0.01) before coronary occlusion, this response was blocked by propranolol but not by phentolamine. In contrast, during reperfusion the increase in idioventricular rate induced by left stellate nerve stimulation (to 203 +/- 14) was not inhibited by propranolol but was abolished by phentolamine (79 +/- 10). Intracoronary methoxamine (0.1 microM) in animals depleted of myocardial catecholamines by 6-hydroxydopamine pretreatment did not affect idioventricular rate before coronary occlusion. However, early after coronary reperfusion, methoxamine increased idioventricular rate from 33 +/- 7 to 123 +/- 21 beats/min (P less than 0.01). Thus, enhanced alpha-adrenergic responsiveness occurs during myocardial ischemia and appears to be primary mediator of the electrophysiological derangements and resulting malignant dysrhythmias induced by catecholamines during myocardial ischemia and reperfusion. PMID- 6243139 TI - Calcium transport in the pars recta and thin descending limb of Henle of the rabbit, perfused in vitro. AB - Unidirectional calcium flux (JCa) in the superficial pars recta and thin descending limb of Henle (DLH) was examined by the isolated tubule microperfusion technic using 45Ca as the isotopic tracer. In the pars recta sequential measurements of lumen-to-bath flux (JlbCa) and bath-to-lumen flux (JblCa) revealed: JlbCa 22.4 +/- 4.18, JblCa 7.97 +/- 1.95, and calculated net efflux of calcium (JnetCa 13.0 +/- 1.74 peq min-1 mm-u. To measure JnetCa directly, 45Ca of identical specific activity was used to bathe and perfuse the tubule. These studies revealed: JlbCa 14.1 +/- 1.33, JnetCa 11.2 +/- 1.15, and calculated JblCa 2.91 +/- 0.49 peq min-1 mm-1. The addition of ouabain (10 microM) resulted in a rise in potential difference and a fall in water absorption, but not a statistically significant change in JnetCa. Tubules studies at 25 degrees C bath temperature, showed no significant JnetCa, and upon heating the bath to 37 degrees C, showed JnetCa of 3.75--5.00 peg min-1 mm-1. Unidirectional and net efflux studies in six DLH showed no significant transport of calcium. These studies demonstrate substantial active absorption of calcium by the superficial pars recta, which is not inhibitable by ouabain but is inhibited by lowering bath temperature to 25 degrees C. No significant calcium transport was found in the DLH using identical technics. PMID- 6243140 TI - Partial purification and characterization of a peptide with growth hormone releasing activity from extrapituitary tumors in patients with acromegaly. AB - Growth hormone (GH)-releasing activity has been detected in extracts of carcinoid and pancreatic islet tumors from three patients with GH-secreting pituitary tumors and acromegaly. Bioactivity was demonstrated in 2 N acetic acid extracts of the tumors using dispersed rat adenohypophyseal cells in primary monolayer culture and a rat anterior pituitary perifusion system. The GH-releasing effect was dose responsive and the greatest activity was present in the pancreatic islet tumor. Small amounts of activity were also found in two other tumors (carcinoid and small cell carcinoma of lung) unassociated with GH hypersecretion. Each of the tumors contained somatostatin-like immunoreactivity but the levels did not correlate with the net biologic expression of the tumor. Sephadex G-75 gel filtration indicated the GH-releasing activity to have an apparent molecular size of slightly greater than 6,000 daltons. The GH-releasing activity was adsorbed onto DEAE-cellulose at neutral pH and low ionic strength, from which it could be eluted by increasing ionic strength. The GH-releasing activity was further purified by high pressure liquid chromatography using an acetonitrile gradient on a cyanopropyl column to yield a preparation that was active at 40 ng protein/ml. Partially purified GH-releasing activity, from which most of the bioactive somatostatin had been removed, increased GH release by pituitary monolayer cultures to five times base line. Enzymatic hydrolysis studies revealed that the GH-releasing activity was resistant to carboxypeptidase, leucine-aminopeptidase, and pyroglutamate-amino-peptidase but was destroyed by trypsin and chymotrypsin, indicating that internal lysine and/or arginine and aromatic amino acid residues are required for biologic activity and that the NH2-terminus and CO9H-terminus are either blocked or not essential. The results provide an explanation for the presence of GH-secreting tumors in some patients with the multiple endocrine neoplasia syndrome, type I, and warrant the addition of GH-releasing activity to the growing list of hormones secreted by tumors of amine precursor uptake and decarboxylation cell types. PMID- 6243141 TI - Mechanisms of antibody-dependent cellular cytotoxicity: the use of effector cells from chronic granulomatous disease patients as investigative probes. AB - The present study characterized the antibody-dependent cellular cytoxicity (ADCC) of leukocyte effector cells (neutrophils, lymphocytes, and monocytes) from normal subjects and from chronic granulomatous disease (CGD) patients. CGD phagocytic cells (neutrophils and monocytes) had depressed ADCC activity against antibody coated human erythrocyte (HRBC) targets in suspension cultures indicative of abnormal intracellular postphagocytic killing. However, when phagocytosis was prevented by using a monolayer of antibody-coated HRBC targets, CGD monocytes, neutrophils, and lymphocytes exhibited normal ADCC activity. Similarly, antibody coated HRBC targets in suspension could be lysed normally by CGD effector cells when phagocytosis was inhibited by the addition of in vitro colchicine. Extracellular lysis of autologous antibody-coated lymphoid cell targets in suspension was mediated normally by CGD effector cells. Thus, standard ADCC against HRBC targets in suspension is predominantly indicative of postphagocytic killing and, as such, is dependent upon a normal post-phagocytic respiratory burst of oxidative metabolism which is deficient in CGD neutrophils and monocytes. Extracellular killing of sensitized targets does not appear to be dependent upon the generation of hydrogen peroxide (H2O2) ANd/or superoxide (02-) and is normal in CGD neutrophils and monocytes. Hence, by employing CGD leukocytes as investigative probes in ADCC, fundamental mechanisms of intracellular vs. extracellular expression of cytotoxicity have been delineated. PMID- 6243144 TI - Beta adrenergic receptors in lymphocyte subpopulations. AB - To further evaluate the potential utility of lymphocyte beta adrenergic receptor assays in the study of receptor alterations in human disease, we studied highly purified populations of B and T lymphocytes in peripheral blood to see if differences existed in the concentration or affinity of beta adrenergic receptors and catecholamine-responsive cAMP levels. The mean number of receptors present in particulate fractions of B cells did not differ significantly from the number found in T cells. Similarly, no significant difference in the dissociation constant for (-)[3H]dihydroalprenolol was found. Cyclic adenosine monophosphate (cAMP) accumulation in whole lymphocytes as measured by radioimmunoassay was comparable, although a tendency toward lower basal and stimulated levels in the T cells was evident. The data suggest that differences observed in concentrations of beta adrenergic receptors or catecholamine-responsive cAMP accumulation in lymphocytes from patients with varying illnesses are not likely to be due to differences in the proportions of circulating B and T lymphocytes. PMID- 6243142 TI - Effect of heparin and heparin fractions on platelet aggregation. AB - Porcine intestinal mucosal heparin induced aggregation of platelets in citrated platelet-rich plasma and enhanced platelet aggregation and serotonin secretion induced by other agents. This action of heparin was blocked by substances that elevate platelet cyclic AMP and by EDTA but not by inhibitors of platelet cyclooxygenase. The effect was not inhibited by apyrase or by N-amylthio-5'-AMP and therefore did not require the action of ADP, nor was there activation of platelet phospholipase. Platelet aggregation by heparin required a plasma cofactor different from the cofactor required for ristocetin. Fractionation of heparin yielded preparations that varied in molecular weight and, within a given molecular weight fraction, in affinity for antithrombin III. Fractions of high molecular weight (average 20,000) were more reactive with platelets than were fractions of low molecular weight (7,000). Anticoagulant activity did not parallel the platelet reactivity of heparin fractions. Among high molecular weight fractions, preparations of high or low antithrombin affinity were equally active in induction of platelet aggregation. In low molecular weight fractions, there was an inverse relationship between platelet reactivity and anticoagulant activity in normal platelet-rich plasma, but, in platelet-rich plasma depleted of antithrombin, low molecular weight fractions of high and low antithrombin affinity reacted equally with platelets. These results suggest that formation of an antithrombin-heparin complex protected platelets from aggregation by heparin. Selection of heparin fractions of low molecular weight and high antithrombin affinity may improve anticoagulant therapy and development of thromboresistant heparin-coated artificial materials. PMID- 6243143 TI - Evidence that proteases are involved in superoxide production by human polymorphonuclear leukocytes and monocytes. AB - The possible participation of proteases in superoxide (O2-) production by human polymorphonuclear leukocytes (PMN) and monocytes was explores using various protease inhibitors and substrates. Protease inhibitors of serine proteases and synthetic inhibitors that modify the active site of serine proteases. Substrates used were synthetic substrates of the chymotrypsin type as well as trypsin type of protease. All these inhibitors and substrates inhibited O2- oroduction by human PMN and monocytes induced by cytochalasin E and concanavalin A, though PMN were more sensitive to these inhibitors and substrates than monocytes. Inhibition appeared rapidly even when the inhibitors were added at the same time as the stimulants, during the "induction time of O2-production" or at the time of maximum O2- production, whereas much greater inhibition was observed when the cells were preincubated with the inhibitors. These observations suggest that enzymatically active serine proteases are essential for these phagocytic cells to initiate and maintain the O2- production in response to the stimuli. The inhibitory effect of the inhibitor and substrate for chymotrypsin type protease was greater than that of those substances for trypsin-type protease. Macromolecular inhibitors also inhibited the O2- production. These findings suggest that the serine proteases involved in the O2- production by human PMN and monocytes are similar to chymotrypsin rather than trypsin, and are possibly located at the cell surface membrane. PMID- 6243145 TI - Pituitary adenomas in old age. AB - Pituitaries obtained at unselected autopsies of 152 men and women over 80 years of age, dying of different diseases, have been investigated histologically by using various staining procedures, including the immunoperoxidase technique. In 20 pituitaries, 22 adenomas were found providing evidence that these tumors are common in aging subjects. In 9 adenomas out of 17 cases, the immunoperoxidase technique revealed the presence of prolactin, indicating that prolactin-producing adenomas constitute the most frequently occurring pituitary tumor type in old age. The presence of growth hormone was demonstrated in one adenoma which also contained prolactin. No storage of ACTH, FSH, LH or TSH was found in the tumors. The biologic behavior of pituitary adenomas disclosed as incidental findings in old age remains to be elucidated. These neoplasms may have a slower growth rate, but more work is required to establish whether they differ from those found in younger age groups. PMID- 6243146 TI - Aspects of free radical reactions in biological systems: aging. AB - The role of free radicals and lipid peroxidation is reviewed with regard to the aging process. Free radicals are produced during mitochondrial respiration, during the autooxidation of a variety of biological molecules and chemicals, during irradiation damage, and are found as environmental pollutants. Free radicals induce lipid peroxidation which results in membrane damage, increased disulfide/sulfhydryl ratios, and accumulation of aging pigments. Superoxide dismutase, glutathione peroxidase, vitamin E, vitamin C, and selenium are of importance with respect to free radical and lipid peroxide quenching. During aging, the levels of vitamin C appear to decline in the human, guinea pig, and the mouse. Synthetic antioxidants, added to the diets of mice, have been noted to extend the lifespan and mean half-survivale times. PMID- 6243147 TI - Mechanisms of recovery from viral infections: destruction of infected cells by neutrophils and complement. AB - Highly enriched populations of bovine neutrophils (PMN) were able to destroy herpesvirus-infected cells when in the presence of C. This mechanism of cytotoxicity was termed C-dependent neutrophil-mediated cytotoxicity (CDNC). To demonstrate CDNC required viable PMN, an active source of C, and a target cell expressing viral antigens. Noninfected cells were not susceptible to lysis. Several approaches were used to exclude the presence of antibody as an explanation for the cytotoxicity observed. In a comparison of the effectiveness of different cell types at mediating CDNC, PMN were more effective than macrophages, and lymphocytes were without activity. The results was discussed in terms of the possible in vivo significance of the neutrophil as a cell type capable of mediating recovery from infection, since if a mechanism similar to CDNC occurs in vivo, this could play a role in defense before the time when protective levels of antibody and immune cells are generated. PMID- 6243148 TI - Physical properties of cytomegalorvirus immune complexes prepared with IgG neutralizing antibody, anti-IgG, and complement. AB - Human cytomegalovirus (CMV) strain AD 169 was reacted with IgG antibody (ab) from a CMV-infected renal transplant patient. A portion of he virus was neutralized, but infectious CMV-ab complexes that could be neutralized by adding rabbit anti human IgG (A-IgG) or complement (C) were also generated. The immune complexes were examined, and the following observations were made: 1) CMV ab sufficient to cause 94% neutralization did not induce measurable changes in virion size or density. 2) The CMV-ab complexes increased slightly in size after reaction with A IgG. 3) C increased the size and density of CMV-ab complexes to a greater degree than A-IgG. Virus aggregation did not occur with ab alone or with ab + A-IgG. However, clumping may have occurred in the presence of ab + C. 4) C also damaged virus envelopes, rendering viral DNA sensitive to DNase. 5) CMV-ab complexes absorbed to host cells as efficiently as native CMV. A-IgG or C partially inhibited complex attachment to the cells and increased the rate of release of cell-attached CMV. These findings suggest that virus neutralization may occur in a multistage process by more than one mechanism depending on the immune reagents employed. The physical changes in virus particles caused by A-IgG or C may be contributing factors in the neutralization process. PMID- 6243149 TI - The in vitro effects of Bordetella pertussis lymphocytosis-promoting factor on murine lymphocytes. V. Modulation of T cell proliferation by helper and suppressor lymphocytes. PMID- 6243150 TI - Induction of prostaglandin E release from macrophages by colchicine. AB - Rat peritoneal macrophages released high amounts of prostaglandin E (PGE) when treated in vitro with 10(-7) to 10(-4) M colchicine. PGE production occurred after a lag period of 4 hr and proceeded at a constant rate for more than 24 hr. Lymphocytes could not be stimulated to PGE release by colchicine. Disaggregation of microtubules appeared to be an essential event, since lumicolchicine was inactive and addition of heavy water (D2O) abolished colchicine-induced PGE formation. Cytochalasin B (5 microgram/ ml) did not interfere with PGE production by colchicine during the initial 12 hr, but thereafter it gave rise to an activity capable of degrading or converting newly synthesized PGE. Although details of the mechanisms by which colchicine in association with disrupted microtubules may induce PGE release remain unclear, these observations suggest that components of the cytoskeleton may efficiently influence the biosynthesis of prostaglandins. PMID- 6243151 TI - Neutrophil-platelet interaction mediated by myeloperoxidase and hydrogen peroxide. PMID- 6243152 TI - Neonatal susceptibility to MHV3 infection in mice. II. Role of natural effector marrow cells in transfer of resistance. AB - Protection of newborn mice against MHV3 infection requires the transfer of several cell populations originating from adult syngeneic donors: adherent spleen cells, T lymphocytes, and a third population present in the nonadherent spleen cell fraction, in peritoneal exudates, and in bone marrow cells (M cells). M cells were found to be sensitive to short-term incubation at 37 degrees C and to preincubation with anti-bone marrow antiserum, mitomycin C, puromycin, and aggregated Ig, the latter suggesting the presence of Fc receptors. They were resistant to silica particles but were sensitive to irradiation with x-rays as well as with 89Strontium. Nonadherent spleen cells, however, behaved differently from M cells toward x-irradiation since they were radio-resistant, suggesting that M cells are precursors that require further differentiation or division to participate in MHV3 resistance. Effector M cells responsible for MHV3 resistance display, therefore, some similarities with natural killing cells. They might belong to a group of effector cells operative in regulatory processes or anti tumor surveillance but also may be defense mechanisms against infectious diseases. PMID- 6243153 TI - Viral inhibition of lymphocyte mitogenesis. I. Evidence for the nonspecificity of the effect. AB - We have investigated the mechanism(s) whereby virus particles, when co-incubated with lymphocytes, are able to abrogate mitogen- and alloantigen-driven cell proliferation. Our data indicate that this inhibition is entirely nonspecific with regard to its induction; similar results can be obtained by using any of several different types of infectious virus particles or viruses whose infectivity had been destroyed by irradiation with ultraviolet light. Furthermore, we show that plasma membranes vesicles, which approximate viruses in size, and which are derived from normal cells, can also impede lymphocyte proliferative responsiveness. In the mixed lymphocyte culture (MLC) reaction, the inhibitory effect is apparently due to the action of viruseith virus can inhibit the mitogen-induced proliferation of resh syngeneic spleen cells, even if added to the latter at a ratio as low as 1:250. These results suggest that virus particles induce the activation of suppressor lymphocytes which in turn act on those cells which would otherwise be responsive in mitogenesis assays and in the MLC. PMID- 6243154 TI - Tissue content of adenosine 3':5'-monophosphate and properties of its binding proteins in human neuroblastoma and ganglioneuroma. PMID- 6243155 TI - Modulation of human hematopoiesis by prostaglandins and lithium. PMID- 6243156 TI - Surface redistribution and release of antibody-induced caps in entamoebae. AB - Polyspecific antibodies bound to Entamoeba induced surface redistribution of membrane components toward the uroid region. Capping of surface antigens was obtained with a single layer of antibodies in E. histolytica and E. invadens. This surface segregation progressed to a large accumulation of folded plasma membrane that extruded as a defined vesicular cap. A spontaneous release of the cap at the end of the capping process took place. These released caps contained most of the antibodies that originally bound to the whole cell surface. Two thirds of radiolabeled antibodies bound to the surface of E. histolytica were released into the medium in 2 h. Successive capping induced by repeated exposure of E. invadens to antibodies produced conglomerates of folded surface membrane, visualized as stacked caps, in proportion to the number of antibody exposures. These results indicate the remarkable ability of Entamoeba to rapidly regenerate substantial amounts of plasma membbrane. The properties of surface redistribution, liberation of caps, and plasma membrane regeneration, may contribute to the survival of the parasite in the host during infection. PMID- 6243157 TI - Tuberculoma of the anterior optic pathways. Case report. AB - A tuberculoma, encasing the anterior optic pathways in a neoplastiform growth, was found in a 25-year-old man complaining of severe visual loss, diabetes insipidus, and sexual impotence following tuberculous meningitis. Following biopsy and anti-tuberculosis treatment, a satisfactory restoration of sight in one eye allowed the patient to resume an almost normal life. PMID- 6243158 TI - Screw-type mouth gag for prevention and treatment of postoperative jaw limitation by fibrous tissue. AB - Treatment of a severe tethering of the mandible by surgery and subsequent exercise of the jaw with a newly devised mouth gag, consisting of two blocks of acrylic resin with a screw expander between them, is described. The mandible was gradually forced to open and was retained in the opened position by rotating the screw against the resistance of scar contraction without much pain. Possible development of trismus after excision of a tumor in the lower retromolar area because of surgical injury to the medial pterygoid muscle and postoperative scarring was avoided by means of the appliance. PMID- 6243159 TI - Adenovirus infection and pertussis-like syndrome. PMID- 6243160 TI - Progression of nephroblastomatosis to Wilms tumor. PMID- 6243161 TI - Cystathioninuria and its origin in children with hepatoblastoma. PMID- 6243162 TI - Autonomic neuropathy complicating rheumatoid arthritis. PMID- 6243163 TI - Primary herpes simplex infection following mouth-to-mouth resuscitation. PMID- 6243164 TI - Pharmacologic antagonism of beta adrenergic blockade in dogs. II. Hemodynamic effects of simultaneous intravenous infusion of isoproterenol and dopamine during chronic propranolol administration. AB - Chronic beta adrenergic blockade was induced in eight dogs with 240 to 360 mg of oral propranolol dailty for 2 to 6 weeks. Beta blockade was confirmed by a minimal heart rate response to isoproterenol, 0.06 micrograms/kg/min, in a pentobarbital-anesthetized, open-chest preparation. Subsequent to confirmation of beta blockade, hemodynamic effects of isoproterenol and dopamine were examined individually and in combination. A desirable balance of arterial pressure and cardiac output was achieved by combining isoproterenol, 0.2 to 2.0 micrograms/kg/min, with dopamine, 5 to 20 micrograms/kg/min. This combination increased mean arterial pressure (109 +/- 9 versus 81 +/- 7), cardiac output (4.3 +/- .5 versus 2.8 +/- .3 L/min) and heart rate 156 +/- 4 versus 120 +/- 7) (p less than 0.05). The hemodynamic effects of combined isoproterenol-dopamine were superior to the effects of either drug alone and suggest a method for effective circulatory support of man during chronic beta adrenergic blockade. PMID- 6243165 TI - Hypothyroidism in workers exposed to polybrominated biphenyls. PMID- 6243166 TI - Treatment of SVC syndrome. PMID- 6243167 TI - The neurotoxicity of the rat poison vacor. A clinical study of 12 cases. AB - Oral ingestion of a new rat poison that antagonizes nicotinamide metabolism, N-3 pyridylmethyl-N'-p-nitrophenyl urea (PNU, Vacor), is known to cause diabetes mellitus. I describe neurologic complications of PNU ingestion in 12 patients 19 to 50 years of age who swallowed between 0.39 and 7.02 g of PNU. One died within a day, and five died of chronic complications 40 to 182 days after taking the poison. Apart from the acute hyperglycemic ketoacidosis, the clinical presentation was variable, but orthostatic hypotension, gastrointestinal hypomotility, peripheral neuropathy, and encephalopathy were typical. The peripheral, autonomic, and central-nervous dysfunction could develop either acutely or other several days. It is possible that nicotinamide, given parenterally within minutes, prevents toxicity, but the cases discussed in this paper indicate that the neurologic deficits may progress despite later nicotinamide administration. Neurologic improvement took many months. Full recovery was uncommon, and the orthostatic, hypotension tended to persist. PMID- 6243168 TI - Remission of cerebellar dysfunction after pneumonectomy for bronchogenic carcinoma. PMID- 6243169 TI - Converting-enzyme inhibition and glomerular filtration rate in essential hypertension. PMID- 6243171 TI - Suppression of ACTH by cortisol in dexamethasone-nonsuppressible Cushing's disease. PMID- 6243170 TI - The use of lithium carbonate to reduce infection and leukopenia during systemic chemotherapy. AB - To investigate whether lithium ameliorates the infectious complications that accompany systemic chemotherapy, we studied 45 patients with small-cell bronchogenic carcinoma receiving combination chemotherapy and radiation therapy. Twenty received lithium carbonate, and 25 received no additional therapy. Control subjects experienced more days with neutropenia than the lithium-treated group (2.17 days per 100 patient-days vs. 0.29), more severe febrile episodes (seven patients vs. one patient), more days hospitalized with fever and neutropenia (1.92 per 100 patient-days vs. 0.18), and more infection-related deaths (five vs. none). Infection-free survival was significantly longer in the lithium-treated group than in controls (P less than 0.05). Delay in subsequent chemotherapy was longer (P less than 0.01) and the number of dose reductions greater (P less than 0.01) in the control group. For both leukocytes and neutrophils, the first cycle nadir, mean of all treatment nadirs, and the lowest nadir observed during treatment were significantly higher in the lithium group. Mean mid-cycle monocyte counts were greater in the lithium group (P less than 0.05) and correlated with concurrent serum lithium levels (rs = 0.74, P less than 0.05). We believe that lithium carbonate shows promise as a means of lowering the risk of infection among patients receiving cytotoxic therapy. PMID- 6243172 TI - Case 36-1979: adenocarcinoma of unknown origin. PMID- 6243173 TI - Lymphoma after thymus transplantation. PMID- 6243174 TI - Dihydroergocryptine binding and alpha-adrenoreceptors in smooth muscle. PMID- 6243175 TI - Dihydroergocryptine binding and alpha-adrenoreceptors in smooth muscle. PMID- 6243176 TI - Formation of SV40 specific and H-2 restricted target cell antigen by somatic cell fusion. PMID- 6243177 TI - (-)Baclofen decreases neurotransmitter release in the mammalian CNS by an action at a novel GABA receptor. PMID- 6243178 TI - Is prostacyclin a physiologically important circulating anti-platelet agent? PMID- 6243179 TI - Evolution and gene transfer in purple photosynthetic bacteria. AB - A concern voiced in connection with recent sequencing of cytochrome c from the Rhodospirillaceae or purple non-sulphur photosynthetic bacteria is that molecular information might be of little use in deciphering bacterial phylogeny because of the possibility of lateral transfer of genes and the consequent scrambling of the genetic record. This could be true for many proteins, of course, but the immediate question is, is it true for cytochroms available for comparison? The evidence suggests that this is probably not so. The disagreement between cytochrome c sequences and the standard taxonomy of the Rhodospirillaceae in Bergey's Manual is not a problem. That reference, as its title indicates, is a manual of determinative rather than evolutionary bacteriology. Its goal is a reproducible system for identification of bacteria. If one claims that these determinative categories also have phylogenetic or evolutionary meaning, this is an assertion that must be proven. The argument outlined below suggests that molecular traits may eventually become more a dependable basis for classification of the Rhodospirillaceae than is gross morphology. PMID- 6243180 TI - Do genealogical patterns in purple photosynthetic bacteria reflect interspecific gene transfer? AB - It is generally thought that interspecific (lateral) transfer of genes is so extensive among bacteria that it is difficult, and perhaps impossible, to determine their phylogenetic relationships. Ambler and coworkers reflect this in their suggestion that the relationships seen among cytochrome c sequences of the Rhodospirillaceae are merely the result of a haphazard lateral transfer of the particular gene, and give no indication of the true bacterial phylogenies. However, if comparative analysis of several unrelated macromolecules yields essentially the same phylogenetic tree, then that pattern is extremely unlikely to reflect the lateral transfer of genes. We have also determined 16S ribosomal RNA catalogues for many of the Rhodospirillaceae in investigated by Ambler et al. and here we use these two sets of data to compare molecular phylogenies for these bacteria. PMID- 6243181 TI - Mental nerve neuropathy: a complication of sickle-cell crisis. AB - Anesthesia of the mental nerve, a rare complication of sickle-cell disease, has been reported. This is the first documented and reported case occurring in the United States. A review of the basic pathophysiology of the disease has been presented. PMID- 6243182 TI - Early detection of childhood malignancies. PMID- 6243183 TI - Pain: its physiology and rationale for management. Part I. Neuroanatomical substrate of pain. AB - Pain, one of man's most worrisome afflictions, is also one of neurobiology's most challenging problems. Even its definition is beset with controversy. The origin and current resolution of this controversy are presented in this paper, but the major purpose of Part I is to review the anatomical substrate of the peripheral and central nervous systems involved in pain. Structural and functional characteristics of pain receptors and their afferent fibers are described, with emphasis upon current hypotheses regarding putative neural transmitters and possible mechanisms for signal transduction. Hitherto unrecognized details of the cytoarchitecture, anatomical organization, and circuitry of the dorsal horns are reviewed. The paper concludes with a consideration of the major components of the ascending and descending systems of subserving pain. PMID- 6243184 TI - Pain: its physiology and rationale for management. Part III. Consequences of current concepts of pain mechanisms related to pain management. AB - Part III of this review describes the impact that acupuncture, our drug culture, and the gate-control theory have had on our progress in elucidating pain mechanisms and in treating pain syndromes. Whether an analgesis is produced by morphine, acupuncture, or electrical stimulation of an appropriate brain region, the analgesia can be blocked by naloxone, a morphine antagonist. This observation, among others, suggests that similar effector mechanisms involving endogenous opiates serve all three types of analgesia. Although the gate-control theory must continually be revised to accord with new information, it has been a major impetus for stimulating fruitful research. PMID- 6243185 TI - Evaluation of transcutaneous electrical nerve stimulation for pain relief in peripheral neuropathy. PMID- 6243186 TI - Intrapetrous carotid artery branches: pathological application. AB - Small intrapetrous internal carotid branches, including the vidian and periosteal arteries, may enlarge in response to hypervascular lesions affecting the posterosuperior nasopharnyx or base of the skull. Periosteal artery hypertrophy indicates extension of lesions, usually neoplasms, to the carotid canal. Vidian artery hypertrophy may occur with either neoplasms or collateral arterial demand between intracranial and extracranial circulations. Such collateral routes may have special relevance when interventional embolization procedures are being considered. PMID- 6243187 TI - Hepatomas seen on follow-up angiograms in patients with liver cirrhosis. AB - Four cases of hepatoma seen on follow-up angiograms of patients with liver cirrhosis are described. Hepatic angiography is the most useful method of detecting a hepatoma complicating liver cirrhosis, and it should be repeated following any minimal change in the serum alpha-fetoprotein level or when the radionuclide image suggests hepatoma, since a small hepatoma may be resectable. PMID- 6243188 TI - Calmodulin plays a pivotal role in cellular regulation. AB - The role of calcium ions (Ca2+) in cell function is beginning to be unraveled at the molecular level as a result of recent research on calcium-binding proteins and particularly on calmodulin. These proteins interact reversibly with Ca2+ to form a protein . Ca2+ complex, whose activity is regulated by the cellular flux of Ca2+. Many of the effects of Ca2+ appear to be exerted through calmodulin regulated enzymes. PMID- 6243189 TI - Antibodies to cerebroside sulfate inhibit the effects of morphine and beta endorphin. AB - Morphine and beta-endorphin inhibit the shaking response of pentobarbital anesthetized rats to ice water. Stereotaxically guided administration of antibodies to cerebroside sulfate into the periaqueductal gray region, the most sensitive brain region in which to demonstrate inhibition of this response, antagonizes the effect of morphine and beta-endorphin. These results suggest that cerebroside sulfate may be an integral component of an opiate receptor in rat brain. PMID- 6243190 TI - Human rotavirus type 2: cultivation in vitro. AB - A strain of type 2 human rotavirus (Wa) was grown to relatively high titer through 14 passages in primary cultures of African green monkey kidney (AGMK) cells. This passage series was initiated with virus that had been passaged 11 times serially in newborn gnotobiotic piglets. In contrast, virus present in the stool of patient Wa as well as virus from the first, second, or third passage in piglets could not be propagated successfully in African green monkey kidney cells. Prior to each passage in cell culture, the virus was treated with trypsin and the inoculated cultures were centrifuged at low speed. Cultivation of a type 2 human rotavirus should aid attempts to characterize this virus and to develop a means of immunoprophylaxis for a serious diarrheal disease of human infants. PMID- 6243191 TI - Morphologic types of breast cancer: age, bilaterality, and family history. AB - Morphologic type is not generally included in the study of cancer risk factors. In breast cancer, attention is being given to age at diagnosis. In this study cases were analyzed by morphologic type as well as age at diagnosis for occurrence of bilateral disease and for family history of breast cancer. Of the morphologic types which were more frequent in younger patients--lobular in situ, medullary, and intraductal comedo--only lobular in situ had an increased frequency of bilaterality (fourfold increase). Of these, only patients with intraductal comedo reported familial breast cancer more frequently than the average. Lobular infiltrating carcinoma is diagnosed more frequently in elderly patients and is associated with 2.6 times more bilaterality and increased familial risk. Diagnosis at age 45 to 54 is also associated with increased bilaterality, but the diagnosis of lobular carcinoma has much stronger association with bilaterality than early age at diagnosis. Because of the high risk of bilaterality in lobular neoplasia and in those with a family history of cancer occurring before the menopause, bilateral biopsies and subsequent screening for malignancy should be done in these women. PMID- 6243192 TI - Delayed presentation of testicular tumors. AB - Germ cell testicular tumors constitute a highly lethal group of neoplasms. Although recent diagnostic and therapeutic developments have altered the prognosis in this disease, delay in diagnosis and occasional mismanagement of patients continue to inhibit further improvement in survival. A ten-year retrospective study of germ cell tumors of the testis at West Virginia University Medical Center confirms confirms the need for patient education and physician awareness of the potential seriousness of all testicular masses. A high index of suspicion and an aggressive approach to management are advocated to improve long term survival. PMID- 6243193 TI - Gross appearance of carcinoma of the main hepatic duct and its prognosis. AB - Twenty-three patients with carcinoma of the hepatic hilus, including the upper one-third of the extrahepatic bile duct, were treated by surgical resections. Gross appearances of this lesion are classified into polypoid, nodular, schirrhous constricting and diffusely infiltrating types. Each type has a different resectability and prognosis from the macroscopic point of view. The cell type in all patients was adenocarcinoma. Operation was curative in 100 per cent of four patients with the polypoid type. The chance for survival was definitively better for patients with this type than with the other three. Preoperative percutaneous transhepatic cholangiography as well as endoscopic retrograde cholangiography and celiac angiography can provide an excellent index to the resectability of the tumor and prognosis. Our experience suggests that gross appearance of the tumor may be valid as a prognostic factor in the treatment of the lesion. PMID- 6243194 TI - Mammary tumors from BALB/c mice with a reported high mammary tumor incidence have acquired new mammary tumor virus DNA sequences. PMID- 6243195 TI - Absence of subviral particles and assembly activity in HeLa cells infected with defective-interfering (DI) particles of poliovirus. PMID- 6243196 TI - Effect of the diterpene ester TPA on Epstein-Barr virus antigen- and DNA synthesis in producer and nonproducer cell lines. PMID- 6243197 TI - Enhanced survival of ultraviolet-irradiated herpes simplex virus in human cytomegalovirus-infected cells. PMID- 6243198 TI - Isolation and characterization of a unique C57BL B-tropic virus. PMID- 6243199 TI - RNA from unique and repetitive DNA sequences of Herpesvirus saimiri. PMID- 6243200 TI - In vitro synthesis of structural and nonstructural proteins of Sendai and SV5 viruses. PMID- 6243201 TI - Viral genome synthesis in BHK 21 cells persistently infected with Sendai virus. PMID- 6243202 TI - Pulmonary changes after primary irradiationfor early breast carcinoma. AB - The clinical records and radiographs of 37 patients with carcinoma of the breast (stages I and II) treated with primary radiation therapy without mastectomy were reviewed. In 10 patients, there was a radiographic pattern of increased radiopacity in the lung underlying the treated breast. The margins of the lesion corresponded to those of the tangential radiation ports with a well defined posterior border noted on the lateral chest radiograph. Apical fibrosis (secondary to supraclavicular irradiation) was demonstrated in six other patients. No patient had symptoms referable to the radiation injury. With the increasing use of radiation therapy as initial treatment for early stage carcinoma of the breast, it is important to recognize these radiation changes in the lungs and distinguish them from infection or recurrent tumor. PMID- 6243204 TI - Herpes simplex infection after needle aspiration of a lymph node. PMID- 6243203 TI - Metabolic studies in a child with a pancreatic insulinoma. AB - An 8-year-old boy with a convulsive disorder for 3 1/2 years remined seizure free for 20 months while being treated with phenytoin (diphenylhydantoin) sodium, and then he had a relapse. He first demonstrated hypoglycemia when he fasted prior to being placed on a ketogenic diet. An oral glucose tolerance test indicated fasting and postglucose hypoglycemia and substantial hyperinsulinemia. Somatostatin infusion resulted in a modest increase in plasma glucose levels and a decrease in serum insulin concentrations. A discrete pancreatic mass was demonstrated preoperatively by celiac angiography that on surgical extirpation, proved to be a benign intrapancreatic insulinoma. Evaluation for islet cell tumors is of importance in children with seizure disorders unresponsive to anticonvulsant medication. Furthermore, somatostatin may be useful preoperatively in maintaining normal blood glucose concentrations in patients with islet cell adenomas. PMID- 6243205 TI - The Chediak-Higashi syndrome; the nature of the giant neutrophil granules and their interactions with cytoplasm and foreign particulates. I. Progressive enlargement of the massive inclusions in mature neutrophils. II. Manifestations of cytoplasmic injury and sequestration. III. Interactions between giant organelles and foreign particulates. AB - Defective bactericidal functioning of polymorphonuclear leukocytes (PMNs) from patients with the Chediak-Higashi syndrome (CHS) has been related in previous reports to a failure of the giant granules characteristics of the disorder to participate in degranulation after uptake of foreign particulates by neutrophils. However, the reason massive CHS inclusions do not fuse with and discharge their contents into phagocytic vacuoles has not been defined. The problem is particularly puzzling because it has been postulated that the hugh organelles in CHS neutophils originate by fusion of small azurophilic granules in promyelocytes and myelocytes. The present series of investigations into the cytopathology of the CHS has employed electron microscopy and ultrastructural cytochemistry to characterize the progressive enlargement of the hugh bodies in mature PMNs, their interaction with cytoplasmic constituents resulting in various manifestations of cell injury, and their response to foreign particulates. Each study clarifies abnormal features of the giant organelles essential to the understanding of their role in the defective bactericidal function of CHS neutrophils. The first report demonstrates that most of the hugh inclusions in PMNs are not primary lysosomes. The interaction and fusion of giant azurophilic granules with each other, with normal-sized primary and secondary granules, and with cytoplasmic components converts the massive primary granules into huge secondary lysosomes. Transformation to secondary hysosomes represents a critical alteration in the state of the giant granules that underlies their damaging influence on the cytoplasm and loss of reactivity wtih phagocytic vacuoles. PMID- 6243206 TI - Replication of murine cytomegalovirus in reproductive tissues. AB - Murine cytomegalovirus (MCMV) was found in preproductive tissues of newborn mice acutely infected with this virus. Using 3H-labeled complementary RNA (cRNA) probe made from MCMV DNA, viral genetic material clearly occupied ovarian stromal cells surrounding the follicular region but not cells of the follicle or cells in the outer tunic layers. In the testes, squamous epithelial cells external to the tunica albuginea harbored viral genetic material. The immaturity of germ line cells in testes of one-week-old mice precluded identification of these cells or examination of their involvement. The presence of viral DNA in reproductive tissue during acute infection raised the possibility that the ovary and/or testes might act as a reservoir for latent virus later in life of adult mice. Hybridization kinetics analysis of DNA isolated from ovaries and testes of 5- and 6-month-old mice latently infected with MCMV suggested that the viral genome was present in both organs. PMID- 6243207 TI - Pancreatic polypeptide as screening marker for pancreatic polypeptide apudomas in multiple endocrinopathies. AB - Prospective screening was carried out in 12 members of three families with multiple endocrine adenopathies, type I (MEA,I) and in 14 patients with no multiple endocrine adenopathies with and without other endorcinopathies. Elevated basal and responsive (after a meal) plasma concentrations of a relatively new candidate-hormone, human pancreatic polypeptide (hPP), were associated with pancreatic apudoma tumors in three asymptomatic patients with multiple endocrine adenopathies, type I. Two of these patients had excision of the tumors that resulted in normal plasma hPP concentrations postoperatively. Both tumors contained hPP predominantly by immunocytochemistry; one, a pure pancreatic polypeptide apudoma, was studied extensively demonstrating also by radioimmunoassay a high content of hPP and negligible amounts of insulin, glucagon, somatostatin, vasoactive intestinal polypeptide and gastrin. In this patient plasma concentrations of other polypeptides including insulin, glucagon, somatostatin, vasoactive intestinal polypeptide, gastrin, parathyrin, thyrocalcitonin, prolactin, corticotropin, growth hormone, thyrtropin and amine, serotonin, were within normal limits. The other patient, after excision of an hPP detected pancreatic mixed hPP-gastrinoma, also became eugastrinemic postoperatively. Normal basal plasma hPP concentrations, but with exaggerated hPP responses to a meal in 11 patients, were associated with various combinations of islet cell hyperplasia, antral G cell hyperplasia with moderate hypergastrinemia and parathyroid hyperplasia. The patients with multiple endocrine adenopathies who have demonstrated this type of increased hPP response to a meal have not been operated on but are at risk for islet hyperplasia. Four of the 12 patients with multiple endocrine adenopathies, type I, with both normal basal and normally responsive hPP concentrations have no evidence as yet of pancreatic involvement. PMID- 6243208 TI - Pain: theory, research and nursing practice. PMID- 6243209 TI - Myeloid bodies in patients without clinical Fabry's disease. AB - Electron microscopy of renal biopsy specimens obtained from three patients revealed typical laminated electron-dense bodies (myeloid bodies) previously believed to be diagnostic of Fabry's disease. None of the patients manifested clinical features characteristic of this disorder, and in one patient leukocyte alpha-galactosidase levels were normal. In comparison with patients with either the heterozygous or homozygous expression of Fabry's disease, in our patients the myeloid bodies were much fewer in number. These observations suggest that the findings of occasional myeloid bodies in renal biopsy specimens should be interpreted with caution. PMID- 6243210 TI - Cystadenoma of the pancreas with cytomegalovirus infection in a female infant. AB - Cystadenoma of the pancreas, principally a disease of adult women, was found in a female infant. This benign, nonfunctional tumor is usually amenable to surgery and a cure is to be expected after extirpation. The pathogenesis of this mass is unknown, but the finding of a cytomegalovirus infection in an excretory duct at the tumor base in this case leads us to speculate that obstruction of the excretory duct is a possible cause. PMID- 6243211 TI - Primary virus isolation by a satellite laboratory. AB - A hospital-based satellite laboratory designed to isolate viral pathogens frequently found in renal transplant and hematology-oncology patients was compared with a system based on isolation by a state-wide reference laboratory. The hospital-based laboratory identified 12 viral isolates from the total 97 clinical specimens submitted. The hospital-based laboratory identified seven viral isolates from the first 50 clinical specimens, whereas the statewide reference laboratory identified six isolates from identical paired specimens. The average time from specimen collection to reporting results for the 97 specimens was 9.2 days for the hospital laboratory, as compared with 11.2 days for the first 50 duplicate specimens sent to the state laboratory. The cost per clinical specimen was $18.10, which compares favorably with costs for routine aerobic bacteriology. The use of a satellite laboratory system for primary viral isolation appears to provide rapid, accurate, and accessible viral diagnosis at an affordable cost. PMID- 6243212 TI - Analytical subcellular fractionation of rabbit alveolar macrophages with particular reference to the subcellular localisation of pyridine nucleotide dependent superoxide-generating systems and superoxide dismutase. AB - Normal and Bacillus Calmette-Guerin (BCG) vaccine-induced rabbit alveolar macrophage homogenates were fractionated by isopycnic density gradient centrifugation. Superoxide dismutase-inhibitable NAD(P)H-dependent nitro-blue tetrazolium reductase was found localised to endoplasmic reticulum and mitochondria. The normal macrophages tended to contain more of this activity than the BCG-induced macrophages. Two superoxide dismutases were found: cyanide sensitive superoxide dismutase was predominantly present in the cytosol, with a small proportion in mitochondria; cyanide-resistant superoxide dismutase was found confined to mitochondria. Neither differed in specific activity betw-en the normal and BCG-induced macrophages. PMID- 6243213 TI - The effects of calcium ionophore A23187 on interstitial cell steroidogenesis. AB - The present study was performed to evaluate the effects of calcium ionophore A23187 on adenosine 3',5'-monophosphate (cyclic AMP) and testosterone production in rat interstitial cells. Interstitial cells were incubated in Krebs-Ringer solution with varying amounts of luteinizing hormone, pregnenolone, or A23187. Cyclic AMP and testosterone were measured in the incubation medium after 4 h incubation. A23187 (0.01--10 microgram/ml) caused progressive increases of cyclic AMP formation (from 0.18 +/- 0.02 (S.E.) pmol/10(6) cells for the control of 0.42 +/- 0.02 pmol/10(6) cells, P less than 0.025), while testosterone production remained unaltered. When varying amounts of A23187 were added concomitantly with luteinizing hormone (5 IU/l), A23187 inhibited luteinizing hormone-induced steroidogenesis in a dose-dependent manner, but it had no effect on luteinizing hormone-induced cyclic AMP formation. When pregnenolone (10(-6) M) was added to the cells, testosterone formation increased from 1.50 +/- 0.22 to 8.46 +/- 1.65 ng/10(6) cells. A23187 (1 microgram/ml) had no discernable effect on the conversion of pregnenolone to testosterone. The main effect of increased cytosol calcium on steroidogenesis seems to be at the steps beyond adenylate cyclase cyclic AMP. These results suggest that calcium is important for the conversion of cholesterol to pregnenolone, while the steps beyond pregnenolone are relatively independent of Ca2+. PMID- 6243214 TI - Regulation of ovarian 17 beta-hydroxysteroid dehydrogenase activity by gonadotropin. AB - Serum testosterone levels are elevated prior to the lutropin surge, and decline abruptly following the release of endogenous lutropin. To investigate this phenomenon, the activity of 17 beta-hydroxysteroid dehydrogenase, the enzyme directly related to testosterone production from androstenedione, was measured. This was done in immature rats in which follicular maturation and ovulation were induced by pregnant mare serum gonadotropin administration. It appears that the effect of the gonadotropin on the enzyme activity is sharply divided into two phases that match with the follicular and the luteal phases. One day following gonadotropin administration, there was already a 7.67-fold increase in the original activity which further increased 48 h following hormone administration. At the peak of the lutropin surge, when follicular development is at its maximum, a 18.44-fold increase was measured. The activity fell abruptly 10 h following ovulation, at a time when fresh corpora lutea are already present in the ovary. It seems that the elevation of serum testosterone followed by its abrupt decline, is directly related to the increased and decreased ovarian 17 beta-hydroxy steroid dehydrogenase activity. The possible importance of the observed changes to the mechanism of the onset of puberty are discussed. PMID- 6243215 TI - Gonadotropin-releasing hormone receptor binding in bovine anterior pituitary. AB - Synthetic gonadotropin-releasing hormone (GnRH) was monoiodinated at a high specific radioactivity with 125I. The iodinated hormone retained full biological activity as assessed by the release of luteinizing hormone in vitro from bovine anterior pituitary tissue slices. Specific binding of 125I-labeled gonadotropin releasing hormone of high affinity and low capacity was obtained using dispersed bovine anterior pituitary cells. The binding had sigmoid characteristics, compatible with the presence of more than one binding site. The subcellular fraction responsible for binding was identified with the plasma membranes. However, significant binding also occurred in the secretory granules fraction. The plasma membranes were solubilized with sodium dodecyl sulfate. Using gonadotropin-releasing hormone covalently coupled to a solid phase, a protein was purified by an affinity technique from the solubilized plasma membrane preparation which possessed similar binding propperties as plasma membranes, both intact and solubilized. The protein migrated as a single component on polyacrylamide gel in sodium dodecyl sulfate and the estimated molecular weight was 60 000. The character of the gonadotropin-releasing hormone concentration dependence binding as well as association kinetics were multiphasic and suggested the presence of more than one binding site. When analyzed by the Hill plot, the Hill coefficient of all binding curves was always greater than one which is compatible with positive cooperativity. This was further supported by the dissociation studies where the dissociation rate was inversely proportionate to both the gonadotropin-releasing hormone concentration and the time interval during which the gonadotropin-releasing hormone-gonadotropin-releasing hormone receptor protein complex was formed. Using difference chromatography, aggregation of the purified gonadotropin-releasing hormone receptor protein was demonstrated to occur upon its exposure to gonadotropin-releasing hormone. The formed macromolecular complexes bound preferentially 125I-labeled gonadotropin-releasing hormone. It is concluded that a single receptor protein is responsible for gonadotropin-releasing hormone binding in the bovine anterior pituitary. It is a part of the plasma membranes. Its interaction with gonadotropin-releasing hormone provokes transitions of the protein into different allosteric forms and this may be related to the biological effect of gonadotropin-releasing hormone on gonadotropin secretion. PMID- 6243216 TI - Preparation of immobilized phosphodiesterase from calf spleen and its use in oligonucleotide analysis. AB - The phosphodiesterase from calf spleen (EC 3.1.4.18) was immobilized on several supports. Some properties of the most suitable enzyme support system--calf spleen phosphodiesterase bound to agarose-Concanavalin A--were investigated, e.g., pH dependence, influence of ionic strength of the buffer medium, and Zn2+-ion inhibition. The immobilized spleen phosphodiesterase showed about 60% of the activity of the free enzyme; the activity toward several oligonucleotide test substrates was unchanged for two months. PMID- 6243217 TI - Auer-bodies in acute lymphocytic leukemia (ALL) PMID- 6243218 TI - Characterization by immunoperoxidase of the lymphocytes with bundle-shaped tubular (BST) inclusions in human normal peripheral blood. AB - In six normal subjects, no surface immunoglobulins were detected on blood lymphocytes containing bundle-shaped tubular (BST) inclusions, after incubation with anti-human IgM peroxidase-labeled Fab'2 fragments. These Fab'2 fragments from pepsin-digested sheep anti-human immunoglobulins revealed human mu kappa, and lambda chains. These results suggest that the BST inclusions do not belong to B lymphocytes but belong to T cells and/or a third lymphocyte population, including K cells and precursors of T and B cells. PMID- 6243219 TI - Activity and activation of the granulocyte superoxide-generating system. PMID- 6243220 TI - Heterosynaptic stimulation modulates the duration of post-tetanic potentiation at an Aplysia synapse without affecting other aspects of synaptic transmission. AB - Repetitive stimulation of an axon in the right visceropleural connective to the abdominal ganglion of Aplysia californica produces post-tetanic potentiation (PTP) of a unitary monosynaptic EPSP recorded from cell R15. PTP decays within one half hour following cessation of repatitive stimulation. Stimulation of the left visceropleural connective speeds the rate of decay of PTP, but does not affect the amount of potentiation which is developed or the size of the non potentiated EPSP. The effect of heterosynaptic left connective stimulation is similar to the previously reported effects of low doses of serotonin but different from the effects of heterosynaptic branchial nerve stimulation. As previously reported, branchial nerve stimulation causes a reduction in the size of the EPSP, and can also speed the rate of decay of PTP. Effects of branchial nerve and left connective stimulation are blocked by SQ10,631, a serotonin antagonist. The left connective effect on the rate of decay of PTP, like the serotonin effect, appears to be mediated by a cyclic nucleotide. The data are consistent with the existence of two separable serotonergic receptors presynaptic to the homosynaptic pathway; one receptor mediates a change in the rate of decay of PTP, one mediates a change in the size of the EPSP. The possible physiological significance of heterosynaptic control of PTP is considered. PMID- 6243221 TI - Guanosine triphosphate: an endogenous compound in the rabbit cerebellar cortex which couples the beta-adrenergic receptor to adenylate cyclase. AB - The guanyl nucleotides GTP and GDP are endogenous factors in the rabbit cerebellum which contribute to the in vitro coupling of the beta-adrenergic receptor to adenylate cyclase. Repeated washing of the particulate material removes these endoactivity to beta-adrenergic agonists. The endogenous GTP and GDP, isolated by high pressure liquid chromatography, mimic the ability of the supernatant both to restore the coupling of receptor and enzyme and to increase basal enzyme activity. The effectiveness of GDP reflects its conversion to GTP during the assay. GTP does not affect either the number of [3H]dihydroalprenolol binding sites or the affinity of these sites for L-isoproterenol; furthermore, GTP does not cause a shift in activation affinity of enzyme activity for isoproterenol. Thus, the guanyl nucleotides are endogenous constituents of the mammalian brain which are essential for the functional 'coupling' of beta adrenergic receptors to adenylate cyclase. PMID- 6243222 TI - Bicyclic phosphates increase the cyclic GMP level in rat cerebellum, presumably due to reduced GABA inhibition. AB - Isopropyl bicyclic phosphate (IPTBO) (0.06 mg/kg i.p.) increased the content of cyclic GMP in rat cerebellar cortex 4-fold. Pretreatment with the nicotinamide antagonist 3-acetylpyridine (3-AP) 65 mg/kg i.p. 48 h before), which destroys the climbing fibers, did not antagonize the induced increase. In contrast, GABA (15 mumol intraventricularly) and muscimol (3 mumol and 10 mumol i.p.) abated the IPTBO induced increase of cyclic GMP. The Na+-independent receptor binding of GABA to synaptosomal membranes, as well as uptake and release of GABA in synaptosomes, were unaffected by IPTBO, but the binding of dihydropicrotoxinin to brain membranes was blocked by IPTBO (IC50 = 1 X 10(-6) M). Glutamate (3.75 or 7.5 mumol intraventricularly) increased the level of cyclic GMP in the cerebellum, but the glutamate level in the cerebellum was not affected by IPTBO (0.06 mg/kg). The present results suggest that the elevation of cerebellar cyclic GMP caused by the bicyclic phosphates is not due to activation of the climbing fibers but rather due to a GABA antagonistic effect. The mechanism of action of the bicyclic phosphates is possibly similar to that of picrotoxinin. PMID- 6243223 TI - A fluorescent analogue of propranolol does not label beta adrenoceptor sites. PMID- 6243224 TI - Picrotoxin block of a depolarizing ACh response. PMID- 6243225 TI - Effect of membrane polarization and synaptic activity on the timing of antidromic invasion. AB - The latency from the stimulus (S) to the IS and SD components of the antidromic spike was measured in motoneurones and spinocerebellar tract cells following displacement of the membrane potential either by current pulses or by synaptic potentials. Changes in the latency to the SD spike (S-SD delay) were mainly caused by changes in the IS-SD delay and varied from 10 to 100 musec per mV change in membrane potential, depending on the initial value of the IS-SD delay. Changes in the S-IS delay were also observed and these changes could, especially in spinocerebellar cells, give a significant contribution to the change in the total delay. EPSPs shortened the S-SD delay as efficiently as current-evoked depolarizations of similar magnitude while IPSPs were often more effective in prolonging the delay than current-evoked hyperpolarizations. This difference was related to the larger conductance increase during IPSPs than during IPSPs and to the longer IS-SD delays at hyperpolarized potentials. The presented data contribute to the understanding of the method which uses extracellular recording of antidromic latency changes as an indirect measure of intracellular membrane potential changes. Our results show that the recording of antidromic latency changes is a particularly sensitive method for detecting inhibition of neurones. PMID- 6243226 TI - Separate serotonin and dopamine receptors modulate the duration of post-tetanic potentiation at an Aplysia synapse without affecting other aspects of synaptic transmission. AB - We have studied the effect of the biogenic amines, serotonin and dopamine, on post-tetanic potentiation (PTP) at an identified synapse in the abdominal ganglion of Aplysia californica. We found that: (1) 10(-7) M perfused serotonin doubles the rate constant of decay of PTP. The effect is specific in that neither the size of the non-potentiated (isolated) EPSP nor the amplitude of PTP is affected. As reported previously, higher doses of serotonin will also increase the amplitude of PTP and decrease the size of the isolated EPSP; (2) 5 X 10(-7) M dopamine in the perfusate increases the rate constant of decay of PTP by about 50%. The effect is also specific in that neither PTP amplitude nor the size of the isolated EPSP is affected; (3) SQ10,631, a serotonin antagonist, blocks the effect of perfused serotonin on PTP decay rate. It does not antagonize the dopamine effect. SQ10,631 also slows the endogenous decay of PTP in some preparations which exhibit an unusually fast PTP decay rate, suggesting a naturally occurring source of serotonin within the ganglion capable of affecting the rate constant of PTP decay; (4) (+)-butaclamol, a dopamine antagonist, blocks the effect of dopamine on the rate constant of PTP decay, whereas (-)-butaclamol has little effect. Butaclamol does not block the effect of serotonin on the rate constant of PTP decay; (5) phosphodiesterase inhibitors potentiate the effect of serotonin on the rate constant of PTP decay, and cyclic AMP analogues mimic the effect of the biogenic amines, suggesting that the aminergic modulation of the rate of decay of PTP is coupled with activation of adenylate cyclase and accumulation of cyclic AMP; and (6) the evidence presented is consistent with the hypothesis that serotonin and dopamine are capable of specifically modifying the rate of change in the efficacy of transmitter release which underlies PTP. It also suggests that the two biogenic amines operate separately and in parallel via presynaptic receptor mechanisms. PMID- 6243227 TI - Demonstration of stereospecific opiate binding in the nervous tissue of the marine mollusc Mytilus edulis. PMID- 6243228 TI - Evidence that substance P is a neurotransmitter of baro- and chemoreceptor afferents in nucleus tractus solitarius. PMID- 6243229 TI - Hippocampal alpha- and beta-adrenergic receptors: comparison of [3H]dihydroalprenolol and [3H]WB 4101 binding with noradrenergic innervation in the rat. AB - The relationship of alpha- and beta-adrenergic receptors to the noradrenergic innervation of the rat hippocampal formation was studied with histofluorescent, biochemical, and radioligand binding methods. The dentate gyrus received a major portion of the innervation and contained twice the norepinephrine content of the hippocampal gyrus. However, the density of beta-adrenergic receptors, determined by [3H]dihydroalprenolol (DHA) binding, was approximately equal in both gyri. By contrast, a presumed alpha-adrenergic binding site was relatively concentrated in the dentate gyrus, roughly correlating with the distribution of the noradrenergic innervation. Although a significant concentration of beta-adrenergic receptors in the pyramidal cell layer had been suggested in previous studies with fluorescent analogs of propranolol, direct microchemical measurements of [3H]DHA binding in stratum pyramidalis and stratum radiatum showed that beta-adrenergic receptors were uniformly distributed in the hippocampal gyrus. These data, demonstrating a ubiquitous distribution of beta-adrenergic binding in a brain region with a well defined noradrenergic input, suggest that a portion, perhaps a majority, of beta adrenergic receptors are not associated with noradrenergic nerve terminals. PMID- 6243230 TI - Effect of cyclic nucleotide derivatives on the release of ACh from cortical slices of the rat brain. AB - Atropine (5 nM to 5 muM), but not D-tubocurarine or hexamethonium, enhanced the release of acetylcholine (ACh) from rat brain cortical slices exposed to high K+. The enhancement was dose-dependent, and it could be partially antagonized by oxotremorine (50-500 muM) or by dibutyryl or 8-bromo-cyclic GMP (1 mM), but not by tetrodotoxin (200 nM) or by dibutyryl cyclic AMP (1 mM). The effects of oxotremorine and the cyclic GMP derivatives were not due to diminished ACh synthesis, since these compounds did not influence the reduction of tissue ACh resulting from treatment with K+ and atropine. These results suggest that cyclic GMP may mediate the regulation of ACh release by presynaptic muscarinic receptors. PMID- 6243231 TI - Pharmacological identification of acetylcholine and glutamate excitatory systems in the dentate gyrus of the rat. AB - The responses of dentate granule cells to medial septum (MS) and perforant path (PP) stimulation were examined in urethane anaesthetized rats. MS and PP stimulation evoked an orthodromic activation of granule cells which was correlated with the negative transient of the characteristic field potential elicited from each site. The effects of electrophoretic application of acetylcholine (ACh) and glutamate (Glu) were examined on granule cells identified in this manner. The excitatory action of ACh but not that of Glu was antagonized by atropine. Glutamate diethylester (GDEE) blocked the excitation produced by Glu but not ACh. The synaptically evoked excitation elicited by MS was blocked by atropine but unaltered by GDEE whereas the PP excitatory response was blocked by GDEE and unaltered by atropine. The results of this study indicate that two discrete excitatory systems are present in the dentate gyrus of the rat: a cholinergic system originating in the medial septum and a glutamate mediated system originating in the entorhinal cortex. PMID- 6243232 TI - The fine structure of large intensely fluorescent catecholamine-containing bodies in aged mouse brain. PMID- 6243233 TI - Adenosine and related compounds do not affect nerve terminal excitability in rat CNS. PMID- 6243234 TI - GABA receptor binding in cultured mammalian spinal cord neurons. PMID- 6243235 TI - Substance P involvement in the expression of gut dependence on opiates. PMID- 6243237 TI - Correlation of elevated C1q binding activity and carcinoembryonic antigen levels with clinical features and prognosis in bronchogenic carcinoma. AB - The presence of immune complexes and carcinoembryonic antigen (CEA) was investigated in 50 patients with bronchogenic carcinoma at the time of and/or following diagnostic or definitive surgery. Immune complexes were measured by the C1q binding test and CEA by the Z gel method and elevations defined as values in excess of 2 S.D. above the normal mean, greater than or equal to 9.2% for C1q binding activity (C1q-BA) and greater than or equal to 5.0 ng/ml for CEA. The overall incidence of elevated values was 30.7% for C1q-BA and 34.2% for CEA. There was a greater incidence of elevated values of C1q-BA among patients with clinically evident disease. The differences with respect to CEA elevation were not significant due to the fact that 6 of 9 samples with elevated CEA values obtained from patients with no evident disease were in fact associated with the presence of clinically undetectable disease in these patients. Elevation of C1q BA and CEA beyond the immediate postoperative period was predictive of a significantly shorter median survival time. The most significant differences in survival time were seen between patients with normal values for C1q-BA and CEA and those with elevations of one or both parameters, 6.0 vs. 19.5 months (p less than 0.001). Elevation of either parameter during the immediate pre- and postoperative period was not predictive of a poor survival. In terms of clinical application, it appears that CEA estimation had the best predictive value but that the addition of C1q-BA measurement may provide additional prognostic information, particularly in patients who do not have elevated CEA values. PMID- 6243236 TI - Role of somatic afferents in autonomic system control of the intestinal motility. AB - (1) In anesthetized (chloralose-urethane) rats, strong mechanical stimuli which were applied to the abdominal skin always inhibited motility of the small intestine. This reflex is referred to as an 'inhibitory cutaneo-intestinal reflex'. Similar stimuli applied to the skin of the upper chest, neck, forepaws, or hindpaws, however, evoked the opposite effect, which is referred to as a 'facilitatory cutaneo-intestinal reflex'. (2) By recording the activity of efferent sympathetic nerves to the small intestine and by transecting intestinal sympathetic or parasympathetic nerves we found that the inhibitory cutaneo intestinal reflex was largely due to an increase in intestinal sympathetic efferent activity, and that the facilitatory cutaneo-intestinal reflex was due to decrease in the intestinal sympathetic efferent nerve activity; both changes reflexly evoked. (3) The inhibitory cutaneo-intestinal reflex was shown to be a propriospinal reflex which was caused by excitation of group IV (unmyelinated) cutaneous afferent nerve fibers. On the other hand, the facilitatory cutaneo intestinal reflex seemed to be mediated through supraspinal pathways, and was evoked by excitation of mainly group III (A-delta group) cutaneous afferent nerve fibers. (4) Interaction between the cutaneo-intestinal reflex and intestino intestinal reflex was demonstrated. (5) The possibility of a dorsal root reflex contribution to cutaneo-intestinal reflex was eliminated. (6) Significance of the cutaneo-intestinal reflex in neural control of the gastro-intestinal tract was discussed. PMID- 6243238 TI - Epithelioid sarcoma and synovial sarcoma in the same knee. AB - A patient who had had a synovial sarcoma removed from the soft tissues adjacent to his knee subsequently developed an epithelioid sarcoma on the opposite side of the same joint. The epithelioid sarcoma metastasized to lymph nodes, invaded blood vessels and produced death 16 years after it was first discovered. The unique association of these two tumors may be an interesting coincidence or may have some relevance to the histogenesis of epithelioid sarcoma. PMID- 6243239 TI - Malignant fibrous histiocytoma: a retrospective study of 167 cases. AB - A retrospective study of 167 patients with soft-tissue malignant fibrous histiocytoma of the trunk, extremities, and retroperitoneal region revealed twice as many deeply situated tumors as superficial tumors. Malignant fibrous histiocytoma may be subclassified into fibrous, giant-cell, myxoid, and inflammatory variants. The fibrous variant accounted for two-thirds of the lesions. The prognosis is no different among the histologic subtypes. The depth of the tumor significantly affects survival, and three important groups were identified: superficial tumors, superficial tumors that recur in deep locations, and deeply situated tumors. The group with superficial tumors that subsequently did not recur in deep locations had a significantly better 4-year survival rate than did the other two groups (65% versus 34% and 40%, respectively). Patients with distally located tumors had a better 5-year survival rate than did patients with proximally located tumors (73% versus 28%). Local recurrence was found in 51% of patients who had a "complete" excision. Patients with superficial tumors had a higher local recurrence rate (71%) than did those with deep tumors (41%). Few patients with retroperitoneal tumors were long-term survivors; the 5-year survival rate was 14%. PMID- 6243240 TI - Malignant inflammatory histiocytoma (inflammatory fibrous histiocytoma): report of a patient with four lesions. AB - A patient with four subcutaneous inflammatory fibrous histiocytomas is presented. Three of these tumors developed synchronously. The neoplasms were examined by light and electron microscopy and were composed of well differentiated histiocytes, multinucleated histiocytes, and less differentiated cells. The ultrastructural findings support the histiocytic nature of this particular tumor. PMID- 6243241 TI - Malignant Mullerian mixed tumors of the uterus: a study of 21 cases. AB - In a study of 21 malignant Mullerian mixed tumors of the uterus seen at The New York Hospital from 1957 to 1977, we found an unexpectedly high incidence (67%) of heterologous tumors which we attribute to an assiduous search for striated cells. Four patients, all of whom had had heterologous tumors, were free of tumor 3 1/2 to 17 years after diagnosis. The tumors were confined to the corpus and exhibited no more than moderate myometrial invasion. The heterologous element was rhabdomyosarcoma in three cases and osteosarcoma in one. Fifteen cases were treated in the last decade as compared with six in the previous decade. PMID- 6243242 TI - A randomized combined modality trial in small cell carcinoma of the lung: comparison of combination chemotherapy-radiation therapy versus cyclophosphamide radiation therapy effects of maintenance chemotherapy and prophylactiv whole brain irradiation. AB - A randomized trial of combined modality therapy employing combination chemotherapy (cyclophosphamide (CTX) and methotrexate (MTX), CTX, MTX and Vincristine (VCR) and CTX, VCR and high-dose MTX with citrovorum rescue) and radiation therapy was compared to cyclophosphamide and radiation therapy in 258 patients with pulmonary small cell carcinoma. Patients were also rendomized: 1) to determine the effects of prophylactic whole brain irradiation; and 2) to establish the effects of maintenance chemotherapy. Survival, frequency of response and site of relapse were different in patients with limited disease (LD) (disease confined to lung, mediastinum and supraclavicular lymph nodes) when compared with disease spread beyond these sites (extensive disease) (ED). No survival advantage was seen in LD when combination chemotherapy was employed, although the frequency of complete remission was greater with three drugs than with one or two drugs (40% vs. 32%). In ED frequency of response was greater for three drugs than for one and two drugs (60% vs. 40%), but there was no survival advantage. The median survival time for complete responders was similar for limited or extensive disease (12.1 months), but 23.8% were alive at 24 months with LD compared to none with ED. Maintenance chemotherapy significantly prolonged survival by 16.8 months with 33% alive at 24 months compared to 9% who were unmaintained. Prophylactic while brain irradiation prevented brain metastases with only 4% developing this complication as compared to 18% of control subjects, but did not influence survival. PMID- 6243243 TI - Phase II study of 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU, NSC No. 409962) with amphotericin B in bronchogenic carcinoma. AB - Eighteen patients with unresectable bronchogenic carcinoma were treated with amphotericin B (7.5 mg/m2 on day 1, 15 mg/m2 on day 2, and 30 mg/m2 on days 3 and 4) plus BCNU (250 mg/m2 on day 4 following amphotericin B) with courses of therapy repeated every 8 weeks. All patients had metastatic disease, and 5 had received prior chemotherapy. Antitumor responses were observed in 8 patients. Six patients had partial responses (greater than 50% decrease in tumor area): 1 of 3 with small cell undifferentiated carcinoma, 1 of 4 patients with large cell undifferentiated carcinoma, 2 of 7 patients with adenocarcinoma, and 2 of 4 patients with epidermoid carcinoma. Two patients had objective improvement (25- 50% decrease in tumor area): 1 with small cell undifferentiated carcinoma and 1 with epidermoid carcinoma. The median duration of remission was 3 months. The median duration of survival was 7 months for patients achieving partial response, and only 2 months for other patients. Myelosuppression was the dose limiting toxicity. One patient died with hepatocellular dysfunction, possibly related to BCNU. Transient hypotension was observed in 2 patients. We conclude that amphotericin B plus BCNU produced an encouragingly high response rate in patients with bronchogenic carcinoma, and that a randomized phase III trial is warranted to determine whether amphotericin B enhances the antitumor effects of nitrosoureas or other known antitumor agents. PMID- 6243244 TI - A myoepithelial cell line established from a human pleomorphic adenoma arising in minor salivary gland. AB - Transformed cells were isolated by using tissue culture techniques from a human pleomorphic adenoma. They revealed ultrastructurally myoepithelial and intercalated ductal cells as the neoplastic cell components that arose in the minor salivary gland of the palate. All transformed clones were demonstrated by electron microscopic examination to be only one type of cells having fine structures similar to myoepithelial cells with typical myofibrils in the cytoplasm. Of five clones isolated, one clone with stable growth was inoculated into nude mice, resulting in a production of myoepithelioma with mucinous substance. In addition, these cloned cells and myoepithelioma cells derived from one clone were found to express viral particles in the intercellular spaces. These findings indicate that a human myoepithelial cell line carrying tumorigenicity is established from the pleomorphic adenoma. PMID- 6243245 TI - A study of the cellularity and ultrastructure of congenital mesoblastic nephroma. AB - This study reported 10 cases of congenital mesoblastic nephroma (CMN) from Children's Hospital of Pittsburgh: five were the typical fibromatous lesion, two were the cellular variant, and three had both components. Six cases occurred in infants less than one week of age. The degree of cellularity had no correlation with patient or tumor size. Three- to 10-year follow-ups of nine patients showed neither local recurrence nor metastasis. One infant died of generalized bleeding post nephrectomy. Ultrastructural study of seven cases showed mesenchymal cells with varying degrees of fibroblastic and/or myofibroblastic differentiation. PMID- 6243246 TI - Neuroendocrine carcinoma of the paranasal sinus: a morphological and endocrinological study. AB - Four cases of small cell carcinoma of the paranasal sinuses were studied histologically, ultrastructurally, and endocrinologically. All tumors showed features of undifferentiated carcinoma with alveolar patterns but without acinar or squamous differentiation and contained cells possessing endocrine-type small secretory granules, which were indistinguishable from non-neoplastic neurosecretory granules. The three cases also possessed a small number of microtubules, and in one of these fine cytoplasmic filaments were observed. One case showed elevated plasma levels of cortisol and adrenocorticotropic hormone associated with adrenocortical hyperplasia and Crooke's changes of the pituitary gland. Another case showed hypercalcemia with bone metastasis, hypercalcitonemia with a high content of calcitonin in the tumor tissue, calcitonin-positive tumor cells, and C-cell hyperplasia of the thyroid. It was concluded that all four cases should be called neuroendocrine carcinoma, which might be related to neoplasms derived from amine precursor uptake and decarboxylation cell series rarely encountered in the paranasal sinuses. PMID- 6243247 TI - Increased incidence of brain metastases in sarcoma patients. AB - Eleven cases of brain metastases that developed in 114 sarcoma patients are presented. Two of 11 patients presented with brain metastasis at the time of diagnosis and the other nine developed them later. The high incidence of brain metastases in patients with rhabdomyosarcoma (26%) and malignant fibrous histiocytoma (27%), two types of tumor which supposedly metastasize rarely to the brain, is remarkable. The increased incidence of brain metastases may be related to longer survival of sarcoma patients and to the inability of AMN and other drugs used in the treatment of sarcomas to cross the blood-brain barrier. Preventive treatment of brain metastases with drugs active in the CNS or with radiotherapy following the diagnosis of pulmonary metastases, could be useful, especially in patients with rhabdomyosarcoma and malignant fibrous histiocytoma. PMID- 6243248 TI - Antagonism between phorbol myristate acetate and butyric acid on isoproterenol elevation of cyclic adenosine 3':5'-monophosphate and their effects on beta adrenergic receptors in mouse epidermis. AB - Butyric acid enhanced adenosine 3':5'-monophosphate accumulation in both untreated and isoproterenol-stimulated epidermis. A single treatment with 17 nmol of the potent tumor promoter, phorbol myristate acetate (PMA), inhibited cyclic adenosine 3':5'-monophosphate accumulation in isoproterenol and in butyric acid stimulated epidermis. beta-Adrenergic receptors in mouse epidermis were measured by the binding of L-[3H]dihydroalprenolol. The apparent dissociation constant was 52 nM, and 33 fmol L-[3H]dihydroalprenolol were bound per microgram DNA. An increase in receptors was induced in vivo with 200 nmol butyric acid. The induction exhibited a 2-fold maximum at 72 hr and a decline to control values at 120 hr. PMA had no effect on the number or availability of the beta-receptors, nor did it affect the butyric acid induction. The biochemical antagonism between PMA and butyric acid on the beta-adrenergic responsiveness of mouse epidermis may be a result of opposing actions on the coupling of beta-receptors to adenyl cyclase. The alteration in the function of membrane receptors involved in cell metabolism may be responsible for some of the biological effects of PMA and other promoters. PMID- 6243249 TI - Selective killing of transformed cells by exploitation of their defective cell cycle control by polyamines. PMID- 6243250 TI - Inhibition by prostaglandin synthesis inhibitors of the induction of epidermal ornithine decarboxylase activity, the accumulation of prostaglandins, and tumor promotion caused by 12-O-tetradecanoylphorbol-13-acetate. PMID- 6243251 TI - Mammary tumorigenesis in 7,12-dimethybenzanthracene-treated C57BL x DBA/2f F1 mice. PMID- 6243252 TI - Activation of cyclic nucleotide phosphodiesterase from isolated human peripheral blood lymphocytes by mitogenic agents. PMID- 6243253 TI - Separation in distinct subpopulations by elutriation of liver cells following exposure of rats to N-nitrosomorpholine. AB - N-Nitrosomorpholine, administered with drinking water to SD rats at the daily dose of 2.4 mg/kg for 7 weeks, induces persisting changes in the hepatocytes as shown by electron microscopy and cytochemistry. In situ, the hepatocytes exhibit a heterogeneous reaction for glucose-6-phosphatase activity. Cells of large diameter, frequently deficient in this enzyme, contain a well-developed rough and/or smooth endoplasmic reticulum. Adult rat hepatocytes from control and N nitrosomorpholine-treated rats were isolated by enzymatic perfusion. Isolated cell populations in both experimental models were composed of a few contaminating sinusoidal cells; small, intermediate, and large hepatocytes; and doublets or triplets of undissociated cells. Five distinct hepatic subpopulations were separated by elutraition or counterflow centrifugation and analyzed by morphological, morphometric, and cytophotometric methods. Fraction I is composed of small (16 to 18 micrometers) diploid hepatocytes; Fractions II and III consist of homogeneous populations of tetraploid cells (mean diameters, 20.5 and 22.4 micrometers); Fraction IV is enriched with large octoploid cells whose mean diameters reach 25.2 micrometers; and Fraction V contains large cells and cell aggregates. The counterflow centrifugation shows the higher proportion of hypertrophied and polyploid hepatocytes, obtained after carcinogen treatment, in the elutriated Fractions IV and V. The structural integrity of hepatocytes is not affected by the process of elutriation. Large hepatocytes, up to 30 micrometers in diameter, exhibit an abundant smooth endoplasmic reticulum, frequently disposed at the periphery of the cell where it forms a network of anastomosing tubules. Moreover, some of these cells present well-developed rough endoplasmic cisternae, closely associated in large fields. Under the scanning electron microscope, elutriated hepatocytes from control rats show numerous regularly distributed microvilli covering the entire cell surface, whereas hypertrophic hepatocytes from N-nitrosomorpholine-treated rats offer heterogeneous cell surfaces, characterized by the presence of patches of short, closely packed microvilli. PMID- 6243254 TI - Effect of prolactin on lactalbumin production by normal and malignant human breast tissue in organ culture. AB - To determine whether lactalbumin production by normal and neoplastic human mammary tissue is under the same control, the effect of prolactin treatment was studied in organ culture. Of 9 premenopausal normal breast samples, 6 produced lactalbumin in culture, and all 6 responded to prolactin treatment over 4 days. One biopsy of pregnant breast tested also responded to prolactin treatment, producing 200 times more lactalbumin in culture than did normal breast. Two of 4 normal postmenopausal biopsies produced lactalbumin, and one increased synthesis and release after prolonged exposure to prolactin. Of 10 scirrhous carcinomas, 6 produced lactalbumin, but none responded to prolactin treatment. In 2 premenopausal patients, normal breast tissue responded to different concentrations of prolactin, which were without effect on malignant tissue from the same breast. In summary, lactalbumin production in the samples that we have studied can be stimulated in normal but not in malignant breast tissue. This may indicate an absence or deficiency of prolactin receptors in malignant tissue. PMID- 6243255 TI - A thymus-dependent serum factor induces maturation of thymocytes as evaluated by graft-versus-host reaction. PMID- 6243256 TI - Prostaglandin E2 rather than lymphocyte-activating factor produced by activated human mononuclear cells stimulates increases in murine thymocyte cAMP. PMID- 6243257 TI - A fluorometric determination of sphingomyelinase by use of fluorescent derivatives of sphingomyelin, and its application to diagnosis of Niemann-Pick disease. AB - We synthesized fluorescent derivatives of sphingomyelin (N-acyl sphingosylphosphocholine) and used them as substrates for several sphingomyelinases. The following five fluorescent probes, each attached to the terminal carbon atom of the fatty acyl residue, were introduced into sphingomyelin: dansyl, pyrene, carbazole, 4-chloro-7-nitrobenz-2-oxa-1,3-diazole, and anthroic acid. We compared the rates at which the fluoro- and radiolabeled sphingomyelins were hydrolyzed. They were the same with the following three spingomyelinases: (a) a purified enzyme from Staphylococcus aureus; (b) at Triton X100-treated extract of human brain (assayed at pH 7.4 in the presence of Mg2+; and (c) aqueous extracts of brain lysosomes, skin fibroblasts, and amniotic cells, assayed at pH 5.0. Homogenates of skin fibroblasts of a patient with Niemann-Pick disease had practically no activity when assayed at pH 5, with fluorosphingomyelin as substrate. When fluorosphingomyelin was mixed in various proportions with natural sphingomyelin, enzymes from each of the three sources hydrolyzed the two substrates at equal rates. The fluorosphingomyelins can be used to estimate with great sensitivity the sphingomyelinase activity in extracts of tissues or cells, in tears, and probably in hair follicles, as well as diagnose Niemann-Pick disease, either pre- or post-natally PMID- 6243258 TI - Seasonal variation of vitamin D3 and 25-hydroxy vitamin D3 in human serum. PMID- 6243259 TI - Delayed recurrent massive thromboembolism through a vena caval clip after pulmonary embolectomy. AB - A case of recurrent massive pulmonary embolization through a modified Miles' clip two weeks after successful emergency pulmonary embolectomy is reported. Vena caval ligation is probably a safer alternative in these critically ill patients. PMID- 6243260 TI - Bronchial adenoma. Clinicopathologic study and results of treatment. AB - Among 1,700 primary tumors of the lung, there were 53 cases of bronchial adenoma (3.1 percent); 38 (72 percent) of the 53 were typical carcinoids, and the remaining 15 were of a higher grade of malignant neoplasm. There was a slight predominance of female patients, and the age of greatest incidence was between 30 and 50 years (31/53; 58 percent). The most frequent localization was in the main bronchi and in the left bronchial tree. In cases of higher grades of malignant neoplasm, extensive bronchopulmonary resections were performed, while in the less active and less metastatic carcinoids, partial resections were generally performed, using bronchoplastic techniques, sleeve resections, and grafts, except in those cases in which bronchial obstruction had produced extensive and irreversible lesions. Survival at five and ten years after surgery is presented. PMID- 6243261 TI - Peripheral neuropathy associated with ethambutol. AB - A woman developed peripheral neuropathy and optic neuritis while receiving ethambutol in the retreatment of drug-resistant pulmonary tuberculosis. There was prompt improvement in peripheral neuropathy and the ocular symptoms following the withdrawal of the drug. The clinical events in this case suggest that occasionally symptoms of peripheral neuropathy may precede the development of optic neuritis by several months, and thus serve as a warning for the subsequent development of the more serious visual toxicity. PMID- 6243262 TI - Acute vestibular dysfunction in childhood. Central vs. peripheral. AB - Acute, vestibular symptoms in childhood are primarily caused by acute labyrinthitis (end organ dysfunction) or central nervous system diseases such as neoplasia involving the pons or cerebellar nuclei or infection manifested by pontine encephalitis. The evaluation, treatment, and prognosis of end organ versus central disease is so different that the ability to make a bedside, presumptive diagnosis provides an important advance. Both patients presented here had a central vestibulopathy. By paying particular attention to the character of the nystagmus and past pointing, the Romberg test, and the details of the vertiginous history, central disease was the presumptive diagnosis prior to invasive procedures. The neurophthalmological clues are reviewed to demonstrate their value in making more accurate diagnoses in children with acute vestibular dysfunction. PMID- 6243263 TI - Cerebrospinal fluid levels of cyclic nucleotides in non-neoplastic hydrocephalus: preliminary report. AB - Cerebrospinal fluid levels of cyclic nucleotides in children with hypertensive communicating hydrocephalus secondary to leptomeningitis were investigated. 3':5' cAMP and 3':5'-cGMP values were uniformly increased in pre-operative findings, suggesting a "passive" behaviour of the blood brain barrier after the inflammatory lesion. After ventriculo-peritoneal shunt, the mean ratio between the two nucleotides gradually became negative, with a marked increase of cGMP levels, probably related to selective barrier damage. In patients with shunt obstruction, the altered cAMP/cGMP ratio showed a gradual regression towards normal, due to a decrease in the cGMP level. The important role of endocranial pressure changes in the "second messenger" turnover is stressed. PMID- 6243264 TI - Synthesis of collagen by human fibroblasts and their SV40 transformants. PMID- 6243265 TI - Abnormal adrenal responses to adrenocorticotropic hormone in hyperandrogenic women. AB - The plasma concentrations of testosterone (T), dehydroepiandrosterone (D), androstenedione (A), pregnenolone (delta 5P), progesterone (P), 17 hydroxypregnenolone (17-delta 5P), 17-hydroxyprogesterone (17-P), 11 deoxycortisol (S), and cortisol (F) were measured before, and 30 and 60 minutes after, a bolus intravenous injection of 25 units of adrenocorticotropic hormone (ACTH) in nine normal women and in fifteen patients with a variety of manifestations of androgen excess. Patients with androgen excess demonstrated significantly higher mean baseline levels of T, D, A, delta 5P, 17-delta 5P, and 17-P. After a bolus intravenous injection of 25 units of ACTH, higher-than-normal increments were noted for the following steroids: delta 5P (one patient), 17 delta 5P (one patient), D (two patients), P (one patients), 17-P (two patients), and S (two patients). Following ACTH injections, the ratios of increments in plasma steroid pairs were computed to estimate the efficiency of several adrenal enzymes, and evidence suggesting partial deficiency of 3 beta-hydroxysteroid dehydrogenase delta 4-5 isomerase (five patients) and 11 beta-hydroxylase (five patients) was found. In addition, 6 of the 15 patients with androgen excess exhibited an abnormally high increment in D relative to the increment in F. The data show that apparent abnormalities in adrenal steroid biosynthesis are a frequent occurrence in patients with hyperandrogenism. PMID- 6243267 TI - Control of thymidine incorporation in mucosal explants from patients with chronic ulcerative colitis. PMID- 6243266 TI - Effect of phenolphthalein on in vitro rabbit ileal electrolyte transport. PMID- 6243268 TI - Hepatic osteodystrophy: outlook good but some problems unsolved. PMID- 6243270 TI - Influence of exogenous glucocorticoids and ACTH on experimental adrenal autografts. AB - Minced adrenal autografts under the renal capsule in adrenalectomized rats were studied by means of serial plasma corticosterone determination and histologic examination. The effect of daily treatment with dexamethasone with or without daily porcine adrenocorticotropic hormone (ACTH) gel was determined. Control autografted rats regained normal corticosterone levels by the 2nd week and at 80 days showed full regeneration of adrenal grafts. Dexamethasone treatment completely suppressed corticosterone and resulted in striking atrophy persistent at 80 days. Porcine ACTH plus dexamethasone resulted in full regeneration with cellular hypertrophy exceeding that of controls, but the corticosterone levels in samples drawn just before the scheduled ACTH injections were very low because the effect of ACTH gel lasted only 12 hr and endogenous ACTH was suppressed. Plasma levels at 40 days were 22.8 +/- 5.9 (SD) for controls, 3.8 +/- 6.1 for dexamethasone, and 5.1 +/- 4.8 for dexamethasone plus porcine ACTH. The results indicate that ACTH is necessary for the optimal regeneration of implanted adrenal autografts. PMID- 6243269 TI - Beta-adrenergic receptors in ciliary processes of the rabbit. AB - Identification and characterization of beta-adrenergic receptors were attempted in particulate membrane fractions derived from isolated ciliary processes (CP) of rabbit eyes. High-affinity binding sites for 125I-hydroxybenzylpindolol (125I HYP), a beta-adrenergic antagonist, were identified in particulate membrane fractions of homogenized CP that were recovered from discontinuous sucrose density gradients. Adenylate cyclase activity was recovered in the same fraction as the 125I-HYP binding sites. The dissociation constant of 125I-HYP for the high affinity site is 0.25 nM, with a minimum capacity of about 35 fmol/mg of protein. Adrenergic agonists and antagonists, including timolol, 1-alprenolol, d,1 propranolol, 1-isoproterenol, 1-epinephrine, and phentolamine, were examined for their ability to displace 125I-HYP from its binding site. The results were consistent with the identification of the high-affinity 125I-HYP binding sites as beta-adrenergic receptors. This is the first report which identifies by ligand binding techniques beta-adrenergic receptors in CP exclusive of iridial or other uveal tissue and supports the possibility of direct action of beta-adrenergic agents on the formation of aqueous humor. PMID- 6243271 TI - Effect of norepinephrine and isoproterenol on in vitro detrusor muscle contractility and cyclic AMP content. AB - Norepinephrine, isoproterenol, and the phosphodiesterase inhibitor, theophylline, caused relaxation of in vitro dog detrusor strips associated with significant increases in detrusor cyclic AMP content. Bethanechol-induced detrusor contractions and alpha-adrenergic detrusor contractile responses to norepinephrine after propranolol were not associated with changes in cyclic AMP. Cyclic nucleotide metabolic pathways exist in detrusor muscle and offer another investigative approach to bladder dysfunction. PMID- 6243272 TI - Degenerative myelopathy in a cat. AB - Degenerative myelopathy was diagnosed in a 6-year-old cat that had progressive ataxia, posterior paresis, and loss of conscious proprioception over a period of 8 months. Corticosteroid therapy did not alleviate clinical signs, and the cat was euthanatized. Microscopic examination of the spinal cord revealed diffuse degeneration of myelin attended by marked astrocytosis. The degenerative changes were most marked in the thoracolumbar segment. The cause of the degenerative lesions was not apparent. PMID- 6243273 TI - Mechanism of the adenylate cyclase reaction. Stereochemistry of the reaction catalyzed by the enzyme from Brevibacterium liquefaciens. AB - Adenylate cyclase from Brevibacterium liquefaciens (ATCC 14929) catalyzes the formation of the RP-diastereomer of adenosine 3':5'-cyclic monophosphorothioate from the SP-diastereomer of adenosine-5'-(1-thiotriphosphate). The reaction catalyzed by this adenylate cyclase proceeds with inversion of configuration at phosphorus, indicating that the cyclization reaction is direct and does not involve formation of an adenylated enzyme intermediate. PMID- 6243274 TI - Independent actions of gonadotropin releasing hormone upon cyclic GMP production and luteinizing hormone release. AB - Gonadotropin releasing hormone (GnRH) and its potent analog [D-Ser(tBu)6]des Gly10-GnRH N-ethylamide elevate pituitary cyclic GMP levels while stimulating gonadotropin release in cultured pituitary cells. Addition of mycophenolic acid to pituitary cell cultures decreased basal and GnRH-induced cGMP production to undetectable levels, but did not reduce basal or GnRH-stimulated luteinizing hormone (LH) release. Elevation of endogenous cGMP levels by sodium nitroprusside, or addition of cGMP or its potent derivatives, was also without effect on basal or GnRH-stimulated LH release. These findings demonstrate that the elevation of intracellular cGMP during GnRH action does not mediate the release of LH by pituitary cells. PMID- 6243275 TI - A stable Thermus thermophilus iron-sulfur protein containing only one binuclear and one tetranuclear cluster. PMID- 6243276 TI - Oxidation-reduction properties and complexation reactions of the iron-molybdenum cofactor of nitrogenase. AB - The interactions of the iron-molybdenum cofactor, FeMoco, isolated from acid treated Azotobacter vinelandii molybdenum-iron protein (Av1) with EDTA and thiophenol in N-methylformamide solution have been reinvestigated. Our studies show that EDTA alone is sufficient to eliminate the EPR signal of dithionite reduced FeMoco. Neither light/5-deazaflavin nor carbon monoxide are required, which implies that this EPR-silent form of FeMoco does not correspond to the EPR silent, substrate-reducing state of Av1. As EDTA-treated FeMoco does not regain EPR activity on addition of sodium dithionite or thiophenol, it is apparently distinct from the EPR-silent form of either dye-oxidized FeMoco or dye-oxidized Av1. Thiophenol sharpens the EPR signal of dithionite-reduced FeMoco and shifts the g = 3.3 feature to g = 3.6. This shift is complete at 1:1 ratio of thiophenol/Mo atom, while the EDTA effect requires about 40 molecules/Mo atom. Thiophenol and EDTA probably affect different sites of FeMoco. The binding of either reactant does not affect the activity of FeMoco as measured by its ability to reconstitute extracts of A. vinelandii mutant UW45. PMID- 6243277 TI - Binding of peptide substrates and inhibitors of angiotensin-converting enzyme. Importance of the COOH-terminal dipeptide sequence. PMID- 6243278 TI - Partial inactivation of cytochrome c oxidase by nonpolar mercurial reagents. AB - Purified beef heart cytochrome c oxidase is inactivated to the extent of 35 to 50% by the nonpolar mercurial reagents mercuric chloride and ethylmercuric chloride. The inactivation is complete within 5 min. In titrations of activity, the plateau level of inactivation is attained at added ethylmercuric chloride:heme a ratios of about 1:1. Up to 3 mercury atoms/heme a are bound to the oxidase, although only the first of these affects its enzymatic activity. Incubation of the ethylmercury-modified oxidase with sulfhydryl compounds reverses the inactivation, with 2,3-dimercaptopropanol being most effective of the reagents tested. Spectrophotometric and polarographic assays of enzymatic activity show that Km values for the native and the ethylmercury-modified enzymes are practically indistinguishable, and that the partial inactivation observed for the latter is reflected exclusively in a lower value of Vmax compared to that of the native enzyme. Based on these results, we propose that ethylmercuric chloride reacts with a single crucial--SH group per heme a, and that electron transfer processes in the modified product are partially inhibited. PMID- 6243279 TI - Fluorescence studies of the sodium and potassium transport adenosine triphosphatase labeled with fluorescein mercuric acetate and anthroylouabain. PMID- 6243280 TI - Dissociation of the actin.subfragment 1 complex by adenyl-5'-yl imidodiphosphate, ADP, and PPi. AB - The ability of adenyl-5'-yl imidodiphosphate (AMP-PNP), ADP, and PPi to dissociate the actin.myosin subfragment 1 (S-1) complex was studied using an analytical ultracentrifuge with UV optics, which enabled the direct determination of the dissociated S-1. At mu = 0.22 M, pH 7.0, 22 degrees C, with saturating nucleotide present, ADP weakens the binding of S-1 to actin about 40-fold (K congruent to 10(5) M-1), while both AMP-PNP and PPi weakens the binding about 400 fold (K congruent to 10(4) M-1). This 10-fold stronger dissociating effect of AMP PNP and PPi compared to ADP correlates with our data showing that the binding of AMP-PNP and PPi to S-1 is about 10-fold stronger than the binding of ADP. In contrast, the binding constants of ADP, AMP-PNP, and PPi to acto.S-1 are nearly identical (K congruent to 5 x 10(3) M-1). At 4 degrees C, AMP-PNP has only a 3 fold stronger dissociating effect than ADP and, similarly, our data suggest that the binding of AMP-PNP and ADP to S-1 is quite similar at 4 degrees C. AMP-PNP and PPi are, therefore, somewhat better dissociating agents than ADP, but the difference among these three ligands is quite small. These data also show that actin and nucleotide bind to separate but interacting sites on S-1 and that the S 1 molecules bind independently along the F-actin filament with a binding constant of about 1 x 10(7) M-1 at 22 degrees C and physiological ionic strength. PMID- 6243281 TI - The crystal structure of cytochrome c peroxidase. PMID- 6243282 TI - Mechanism of desensitization of adenylate cyclase in lutropin. GTP-dependent uncoupling of the receptor. AB - Lutropin-sensitive adenylate cyclase ((EC 4.6.1.1) ATP pyrophosphate-lyase (cyclizing)) in purified rat ovarian plasma membranes is stimulated by lutropin 2 to 3-fold in the absence, but 15- to 20-fold in the presence of GTP or p(NH)ppG. Following 10 to 15 min of incubation at 30 degrees C in the presence of lutropin, enzyme activity declined (50%) in the presence of GTP but not in the presence of p(NH)ppG. This desensitizing process induced by lutropin and GTP is not seen if NaF is also included in the incubation medium. The desensitized state of the enzyme persists at 4 degrees C in membranes washed free of the incubation medium. In this state the enzyme is characterized by: (i) a reduced response to lutropin even in the presence of p(NH)ppG; (ii) its response to NaF is not different from that of untreated enzyme; (iii) it reconverts to a fully responsive state following incubation (10 min, 30 degrees C) in GTP-free medium, a process accelerated by p(NH)ppG; (iv) the receptor content as well as the stability of the receptor.hormone complex does not differ from that of untreated fully responsive enzyme. It is proposed that desensitization results from a GTP dependent, hormone-stimulated reaction that leads to impaired coupling of the enzyme system. The desensitized state induced is transient and may revert to a responsive one under specified conditions. PMID- 6243283 TI - Studies on the phosphorylation and dephosphorylation of L-type pyruvate kinase by the catalytic subunit of cyclic AMP-dependent protein kinase. PMID- 6243284 TI - Structure of the divalent cation.nucleotide complex at the active site of phosphoribosylpyrophosphate synthetase. AB - When Mg2+ was used as the activating cation, the phosphoribosylpyrophosphate synthetase (EC 2.7.6.1) of Salmonella typhimurium showed absolute specificity for the A(S) enantiomer of adenosine 5'-O-(1-thiotriphosphate), which gave a Km of 72 +/- 10 microM and a Vmax of 111 +/- 5 mumol/min/mg. The corresponding values for ATP were 46 +/- 3 microM and approximately 107 mumol/min/mg. Under the same conditions the B(R) isomer was a linearly competitive inhibitor (Ki = 54 +/- 11 microM) with respect to ATP. When Cd2+ replaced Mg2+, the two isomers reacted at comparable rates (Vmax (A)/Vmax (B) approximately equal to 0.8). This change in specificity suggests that the alpha-phosphate of ATP is liganded to a divalent cation during catalysis. Adenosine 5'-O-thiomonophosphate was 34-fold more effective as a product inhibitor when Cd2+ replaced Mg2+, while the effectiveness of AMP was not altered. This result suggests a divalent cation bridge between the enzyme and the alpha-phosphate of nucleotides. The results of these and previously published experiments enable us to propose a structure and stereochemical configuration for the divalent cation.ATP complex at the active site of phosphoribosylpyrophosphate synthetase. PMID- 6243285 TI - Affinity purification of newly phosphorylated protein molecules. Thiophosphorylation and recovery of histones H1, H2B, and H3 and the high mobility group protein HMG-1 using adenosine 5'-O-(3-thiotriphosphate) and cyclic AMP-dependent protein kinase. PMID- 6243286 TI - Sodium-dependent neutral amino acid transport in native and reconstituted membrane vesicles from Ehrlich cells. PMID- 6243287 TI - Structure, spacing, and phasing of nucleosomes on isolated forms of mature simian virus 40 chromosomes. AB - Mature Simian virus 40 (SV40) chromosomes were isolated from infected CV-1 monkey cells by a hypotonic extraction method that not only allowed replicating viral chromosomes to faithfully continue DNA replication in vitro, but also was found to assemble nascent DNA into nucleosomes with a structure and arrangement typical of native viral chromosomes. Detailed analysis of the DNA and nucleoprotein products from micrococcal nuclease and DNase I digestion of mature viral chromosomes assembled in intact cells showed that the structure of SV40 and CV-1 cellular nucleosomes was the same. Furthermore, the histone composition of viral chromosome was indistinguishable from that of its host. In contrast to the identity in nucleosome structure, nucleosome spacing on isolated SV40 chromosomes was not as regular as on cellular chromatin. When 1% of the DNA was solubilized by micrococcal nuclease, as many as 20 cellular DNA bands were clearly resolved by gel electrophoresis, but only 6 to 7 viral DNA bands were observed and they were broader and less well resolved. In addition, micrococcal nuclease digested SV40 chromosomes at a faster initial rate and to a greater extent than CV-1 chromatin present in the same tube. Either BglI or EcoRI restriction endonuclease cut a single site in 30% of the SV40 chromosomes which suggested that viral nucleosomes were not located in a unique phase with respect to DNA sequence, but appeared to be randomly spaced around the genome. Viral chromosome structure was basically unaltered in hypotonically extracted chromosomes exposed to 200 or 600 mM NaCl and in isotonically extracted chromosomes prepared in the presence of Triton X-100 and EDTA. These results confirm and extend our previous data on the arrangement of SV40 nucleosomes inside isolated nuclei and demonstrate that the structure of viral chromosomes was not altered by the isolation procedures employed. The data are consistent with a model in which an average of 22 nucleosomes, randomly distributed around the SV40 genome, are separated by non nucleosomal spacer regions which account for about 20% of the total DNA. PMID- 6243288 TI - The beta-adrenergic receptor of live human polymorphonuclear leukocytes. PMID- 6243289 TI - Poliovirus increases phosphatidylcholine biosynthesis in HeLa cells by stimulation of the rate-limiting reaction catalyzed by CTP: phosphocholine cytidylyltransferase. PMID- 6243290 TI - An increase in cytoplasmic CTP accelerates the reaction catalyzed by CTP:phosphocholine cytidylyltransferase in poliovirus-infected HeLa cells. AB - Poliovirus increases phosphatidylcholine biosynthesis in HeLa cells by stimulation of the reaction catalyzed by CTP:phosphocholine cytidylyltransferase (Vance, D.E., Trip, E.M., and Paddon, H.B. (1980) J. Biol. Chem. 255, 1064-1069). The mechanism for the virus effect has been investigated. An assay for the cytidylyltransferase which mimics the physiological conditions within the cell was developed. The enzyme activity was not changed at 3 h but was stimulated more than 2-fold at 4 and 5 h after infection with poliovirus. Enzyme activity was stimulated by addition of CTP to the assay. At 0.10 mM CTP the difference in activities from poliovirus- and mock-infected cells was abolished. Mg2+ inhibited the cytidylyltransferase activities and eliminated the differences between the two activities at a concentration of 0.05 mM. However, the endogenous amount of Mg2+ in the postmitochondrial supernatants was the same for infected and mock infected cells. The addition of CDP-choline or PPi inhibited the cytidylyltransferase activity but had no effect on the relative differences in activities from infected and mock-infected cells. Measurement of CTP in the postmitochondrial fraction showed no differences at 3 h but was elevated 2- to 3 fold in poliovirus-infected cells at 4 and 5 h. It appears that the cytidylyltransferase reaction is faster in poliovirus-infected HeLa cells because of an increase of CTP in the cytoplasmic compartment. Moreover, it appears that the concentration of CTP in the cytoplasm can determine the rate of phosphatidylcholine biosynthesis in HeLa cells. PMID- 6243291 TI - Effect of two inhibitors of anion transport on the hydrolysis of glucose 6 phosphate by rat liver microsomes. Covalent modification of the glucose 6-P transport component. PMID- 6243292 TI - Enzymatic activities in cultured human lymphocytes that dephosphorylate dolichyl pyrophosphate and dolichyl phosphate. AB - Enzymatic activities which dephosphorylate dolichyl phosphate (Dol-P) and dolichyl pyrophosphate (Dol-P-P) have been observed in membranes from cultured human lymphocytes. Neither activity requires divalent metals. Dol-P phosphatase is inhibited by inorganic phosphate but not by other phosphate-containing compounds. Dol-P-P phosphatase is inhibited by bacitracin but not by phosphate containing compounds including the methylene analogue of pyrophosphate. These reactions are similar to those previously found in the cycle of bacterial wall peptidoglycan biosynthesis. A chemical synthesis of [32P]Dol-P and [32P]Dol-P-P is reported. PMID- 6243293 TI - Investigations on the association of phosphatidylserine synthase with the ribosomal component from Escherichia coli. AB - The CDP-1,2-diacyl-sn-glycerol (CDP-diacylglycerol):L-serine O phosphatidyltransferase (EC 2.7.8.8, phosphatidylserine synthase) of Escherichia coli is the first enzyme in the pathway committed to the biosynthesis of the major lipid in E. coli, phosphatidylethanolamine. The enzyme is unique among the phospholipid biosynthetic enzymes due to its high affinity for ribosomes in crude extracts. We report here investigations which define the nature of this in vitro affinity for ribosomes. Phosphatidylserine synthase can be dissociated from ribosomes in the presence of various inorganic salts at high ionic strength. Dissociation was also brought about by cellular levels of the polyamine spermidine. These results suggest the interaction of the enzyme with ribosomes in vitro is primarily ionic in nature, and polyamines may prevent this interaction in vivo. In the presence of nonionic detergent-lipid substrate mixed micelles under assay conditions the enzyme is also dissociated from ribosomes. Dissociation does not occur in the presence of detergent alone or in the presence of lipids which are not substrates or products of the enzyme. This dissociation by lipid substrate indicates the enzyme is not associated with ribosomes during catalysis. PMID- 6243294 TI - Regulatory subunit of the type I cAMP-dependent protein kinase as an inhibitor and substrate of the cGMP-dependent protein kinase. AB - The regulatory subunit of the type I cAMP-dependent protein kinase (Rt) serves as a substrate for the phosphotransferase reaction catalyzed by cGMP-dependent protein kinase (Km = 2.2 microM). The reaction is stimulated by cGMP when RI . cAMP is the substrate, but not when nucleotide-free RI is used. The cGMP dependent protein kinase catalyzes the incorporation of 2 mol of phosphate/mol of RI dimer in the presence of cAMP and a self-phosphorylation reaction to the extent of 4 mol of phosphate/mol of enzyme dimer. In the absence of cAMP, RI is a competitive inhibitor of the phosphorylation of histone H2B (Ki = 0.25 microM) and of the synthetic peptide substrate Leu-Arg-Arg-Ala-Ser-Leu-Gly (Ki = 0.15 microM) by the cGMP-dependent enzyme. Nucleotide-free RI also inhibits the intramolecular self-phosphorylation of cGMP-dependent protein kinase. The inhibition of the phosphorylation reactions are reversed by cAMP. The catalytic subunit of cAMP-dependent protein kinase does not catalyze the phosphorylation of RIand does not significantly alter the ability of RI to serve as a substrate or an inhibitor of cGMP-dependent protein kinase. These observations are consistent with the concept that the cGMP- and cAMP-dependent protein kinases are closely related proteins whose functional domains may interact. PMID- 6243295 TI - Conformation changes of actin during formation of filaments and paracrystals and upon interaction with DNase I, cytochalasin B, and phalloidin. AB - Spin labels attached to rabbit muscle actin became more immobilized upon conversion of actin from the G state to the F state with 50 mM KCl. Titration of G-actin with MgCl2 produced F-actin-like EPR spectra between 2 and 5 mM-actin filaments by electron microscopy. Higher concentrations of MgCl2 produced bundles of actin and eventually paracrystals, accompanied by further immobilization of spin labels. The effects of MgCl2 and KCl were competitive: addition of MgCl2 to 50 mM could convert F-actin (50 mM KCl) to paracrystalline (P) actin; the reverse titration (0 to 200 mM KCl in the presence of 20 mM MgCl2) was less complete. Addition of DNase I to G- or F-actin gave the expected amorphous electron micrographic pattern, and the actin was not sedimentable at (400,000 x g x h). EPR showed that the actin was in the G conformation. Addition of DNase I to paracrystalline actin gave the F conformation (EPR) but the actin was "G" by electron microscopy. Phalloidin converted G-actin to F-actin, had no effect on F actin, and converted P-actin to the F state by electron microscopy but maintained the P conformation by EPR. Cytochalasin B produced no effects observable by EPR or centrifugation but "untwisted" paracrystals into nets. Since actin retained its P conformation by EPR in two states which were morphologically not P, we conclude that the P state is a distinct conformation of the actin molecule and that actin filaments aggregate to form bundles (and eventually paracrystals) when actin monomers are able to enter the P conformation. PMID- 6243296 TI - Characterization and purification of a calcium-sensitive ATP diphosphohydrolase from pig pancreas. AB - An ATP diphosphohydrolase (EC 3.6.1.5) from the pancreas of the pig has been characterized and purified. The enzyme which has an optimum pH between 8 and 9 is specific for diphospho- and triphosphonucleosides. The Km values for ADP and ATP are 7.4 and 7.3 x 10(-4) M, respectively, and the purified enzyme has specific activities of 13 and 15.2 mumol of Pi/min/m of protein, respectively. It requires calcium or magnesium ions and it is insensitive to ATPase inhibitors, namely oligomycin, ouabain, and ruthenium red, and to levamisole, an inhibitor of alkaline phosphatase. Denaturation experiments, by heat and trypsin treatments, indicated that only one enzyme is involved. This is confirmed by the solubilization and purification process and by polyacrylamide gel electrophoresis. A 270-fold purification was obtained by centrifugation and successive column chromatography on Sepharose 4B and Affi-Gel blue. It is a glycoprotein with a molecular weight of 65,000 as estimated by polyacrylamide gel electrophoresis. PMID- 6243297 TI - Initiation of poly(ADP-ribosyl) histone synthesis by poly(ADP-ribose) synthetase. AB - Initiation of poly(ADP-ribosyl) histone synthesis was achieved in vitro using an apparently homogeneous preparation of poly(ADP-ribose) synthetase. When poly(ADP ribose) was synthesized in the presence of DNA and increase amounts of histone H1, increasing portions (up to about 55%) of the product were found associated with the histone, judging from solubility in 5% HClO4 and sodium dodecyl sulfate polyacrylamide gel electrophoresis. Most of the polymers were directly attached to the histone protein and not produced by elongation from pre-existing ADP ribose; the cohesive end of poly(ADP-ribose), isolated as ribose 5-phosphate with snake venom phosphodiesterase digestion, was labeled almost quantitatively with [ribose (NMN)-14C]NAD. The poly(ADP-ribose) . histone linkage was labile in mild alkali and neutral NH2OH, suggesting that the same bond, probably ester, was formed in this system as in crude chromatin or isolated nuclei. Elongation of a histone-bound monomer into a polymer by this enzyme was previously demonstrated (Ueda, K., Kawaichi, M., Okayama, H., and Hayaishi, O. (1979) J. Biol. Chem. 254, 679-687), but initiation of ADP-ribose chains on histone has never been shown with a purified enzyme. This appeared to be due to the low concentrations of histone so far used. These findings indicated that a single enzyme catalyzes two different types of reaction, i.e. an attachment of ADP-ribose to histone and its elongation into a polymer. PMID- 6243298 TI - A biologically active, three-fragment complex of horse heart cytochrome c. PMID- 6243299 TI - Identification of regions of the catalytic subunit of (Na-K)-ATPase embedded within the cell membrane. Photochemical labeling with [3H]adamantane diazirine. PMID- 6243300 TI - Interaction between pyridoxal kinase and pyridoxine-5-P oxidase, two enzymes involved in the metabolism of vitamin B6. PMID- 6243301 TI - Modification of the 5' end of mRNA. Association of RNA triphosphatase with the RNA guanylyltransferase-RNA (guanine-7-)methyltransferase complex from vaccinia virus. AB - Purified RNA guanylyltransferase . RNA (guanine-7-)methyltransferase complex from vaccinia virus contains RNA triphosphatase activity. The latter activity, which removes the gamma-phosphate from triphosphate-ended polyribonucleotides, co chromatographed with the capping and methylating enzyme complex on seven different ion exchange or affinity columns and co-sedimented with the complex on a glycerol gradient. On a molar basis, the RNA triphosphatase was about 100 times more active than the associated RNA guanylyl-transferase. When the purified enzyme complex was incubated with poly(A) containing a 5'-triphosphate, removal of the gamma-phosphate preceded capping. Furthermore, there was no significant difference in the rate or extent of capping 5'-diphosphate- or 5'-triphosphate ended poly(A). Physical association of the three enzymatic activities appears to be an efficient mechanism for carrying out the following successive steps in cap formation: (formula: see text). PMID- 6243302 TI - Fluoride stimulation of adenylate cyclase is dependent on the guanine nucleotide regulatory protein. PMID- 6243303 TI - A cAMP-dependent phosphorylated motility protein in bovine epididymal sperm. AB - A putative cAMP-dependent protein kinase substrate associated with the cAMP stimulation of bovine sperm motility has been identified. Optimum conditions for a linear, concentration-dependent incorporation of [32P]ATP into phosphoproteins of an epididymal sperm sonicate by cAMP-dependent protein kinase are described. The motility state of the sperm was reduced by incubation at 37 degrees C and reactivated with theophylline. Endogenous levels of cAMP correlated with the motility state of the sperm. The phosphorylation state of phosphoproteins was frozen by addition of NaF (100 mM final concentration). After sonication and removal of endogenous nucleotides, 32P incorporation into phosphoprotein varied inversely with motility. The inverse relationship results from the procedure monitoring the capacity for incorporation of 32P into dephosphorylated cAMP dependent protein kinase substrates. Over 70% of the cAMP-dependent label was in the soluble fraction. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed one cAMP-dependent phosphoprotein from the soluble fraction which had an inverse correlation with motility. This 55,000-dalton protein did not bind [3H]cholchicine (tubulin) or [3H]cAMP (REGULATORY SUBUNIT OF PROTEIN KINASE). These data indicate the existence of a cytosolic phosphorylated motility protein. PMID- 6243304 TI - The role of the guanine nucleotide exchange reaction in the regulation of the beta-adrenergic receptor and in the actions of catecholamines and cholera toxin on adenylate cyclase in turkey erythrocyte membranes. AB - Several changes were noted in the characteristics of the turkey erythrocyte beta adrenergic receptor and in the kinetic properties of adenylate cyclase following pretreatment of erythrocyte membranes with isoproterenol and GMP, and thorough washing to remove these agents. The changes include modifications in the binding of agonist (isoproterenol) and in revelation of marked effects of GTP on agonist binding; reduction in the lag in Gpp(NH)p activation of adenylate cyclase; short lived activation by GTP which is lengthened by treatment with cholera toxin and NAD prior to pretreatment with isoproterenol and GMP. Treatment with cholera toxin also shortened the lag in activation by Gpp(NH)p and increased the steady state levels of activation by both Gpp(NH)p and GTP. The following conclusions can be drawn: (i) catecholamines, in the presence of a guanine nucleotide, stimulate the exchange of bound and exogenous nucleotide; (ii) the exchange reaction is involved in both the activation of adenylate cyclase and in the reciprocal effects of hormone and guanine nucleotides on each other's binding: (iii) the beta-adrenergic receptor and nucleotide regulatory components are linked in turkey erythrocyte membranes; (iv) both cholera toxin and catecholamines, although by different mechanisms, stimulate the exchange reaction at the nucleotide regulatory sites. PMID- 6243305 TI - Glomus tumor of the coccygeal region. Case report. PMID- 6243306 TI - Intertrochanteric osteotomy for osteoarthritis. A long-term follow-up. AB - The results of 757 intertorchanteric osteotomies for osteoarthritis of the hip carried out between 1958 and 1970 were reviewed. After osteotomy the joint space in two thirds of the hips was increased and a similar proportion experienced relief of pain lasting at least five years. However, the effect of the osteotomy declined after some ten years; only a quarter of the hips had a lasting "good result" as defined in this investigation. The best results were obtained in active patients under 70 years of age with unilateral hip disease in which a fair range of movement had been preserved despite some shortening and where the radiographs showed loss of joint space with a break in Shenton's line. In this study a displaced osteotomy fixed with a spline emerged as the most successful surgical technique. PMID- 6243307 TI - Degranulating stimuli decrease the neagative surface charge and increase the adhesiveness of human neutrophils. AB - Chemotactic factors decrease the negative surface charge of neutrophils (polymorphonuclear leukocytes [PMN]) and this has been speculated to be important in PMN margination and aggregation in vivo. PMN adherence and aggregation are also enhanced by degranulation of lysosomal enzymes. To further assess the possible relationship between degranulation, surface charge, adherence, and aggregation, human peripheral blood PMN (isolated by Hypaque-Ficoll and dextran sedimentation) were exposed to the secretagogues ionophore A23187, phorbol myristate acetate, concanavalin A, and chemotactic factors (partially purified C5a or the synthetic peptide f-met-leu-phe) plus cytochalasin B. Surface charge was measured in a cytopherometer. After incubation of PMN with secretagogues, PMN surface charge was decreased to a greater extent than incubation of PMN with chemotactic factors. The decreased surface charge induced by f-met-leu-phe plus cytochalasin B required both extracellular calcium and magnesium. The ionophore A23187-induced surface charge changes were dependent on extracellular calcium but not magnesium whereas the phorbol myristate acetate effect was only partially dependent on Ca(++) and Mg(++). The surface charge changes induced by secretagogues were related to both the amount of lysozyme released and to the increased adhesiveness of cells to plastic surfaces. These observations indicate exocytosis of lysosomal granule contents is associated with decreases in neutrophil surface charge, and there appears to be a correlation between decreases in surface charge and facilitation of neutrophil aggregation and adhesiveness. However, a causal relationship between these events has not been established, and the relationship may be simply temporal. PMID- 6243308 TI - Relationship between secretion of platelet Factor 4 and thrombin generation during in vitro blood clotting. AB - We have studied the effects of both impaired prothrombin activation and direct inhibition of thrombin on the platelet release reaction in clotting blood to determine the role of thrombin in this process. In blood from two patients with congenital Factor V deficiency, prothrombin activation during spontaneous in vitro clotting was delayed and decreased. Secretion of platelet Factor 4 was also delayed and was detected only after thrombin formation was initiated. Addition of a small amount of normal plasma to the patients' blood in vitro corrected the abnormalities in both thrombin formation and the platelet release reaction in parallel fashion. A delay in the onset of secretion of platelet Factor 4 was also observed when thrombin generated in normal blood during spontaneous in vitro clotting was inhibited by either purified hirudin or anti-thrombin Fab. These observations suggest that thrombin is the essential stimulus for platelet secretion during in vitro blood clotting. The effect of inhibitors of the platelet release reaction on prothrombin activation during in vitro blood clotting was also studied. When either prostacyclin or the combination of prostaglandin E(1) and N(6)O(2')-dibutyryl cyclic AMP was added, secretion of platelet Factor 4 was inhibited 85-95%. We were unable to detect any inhibition of initiation of prothrombin activation or inhibition of that part of thrombin generation associated with clotting. These results indicate either that the platelet release reaction may not be required for the initiation of prothrombin activation or only a very limited amount of secretion may be necessary for normal generation of thrombin to occur. PMID- 6243309 TI - Carbenicillin and penicillin G inhibit platelet function in vitro by impairing the interaction of agonists with the platelet surface. AB - Carbenicillin or penicillin G administered in large doses can cause a bleeding diathesis as a result of platelet dysfunction. These antibiotics also inhibit platelet aggregation in vitro, although several-fold larger concentrations of drug are required to demonstrate this effect. We wondered whether these antibiotics might impair platelet function by interfering with the initial step of platelet activation: the binding of agonists to their specific receptors on the platelet surface.Platelet aggregation and [(14)C]serotonin release induced by epinephrine were competitively inhibited by carbenicillin and penicillin G in vitro. At antibiotic concentrations that inhibited platelet function by more than 80%, the affinity of platelet alpha-adrenergic receptors for the alpha-adrenergic antagonist, [(3)H]dihydroergocryptine, and for epinephrine was reduced twofold by carbenicillin and sixfold by penicillin G (P < 0.01). Platelet aggregation and [(14)C]serotonin release stimulated by ADP were also competitively inhibited by these antibiotics. In addition, carbenicillin reduced the incorporation of an ADP affinity label, 5'-p-fluorosulfonylbenzoyl [(3)H]adenosine, into its binding protein in platelet membranes. Moreover, both carbenicillin and penicillin G impaired the interaction of von Willebrand factor with platelets as evidenced by their inhibition of the agglutination of formalin-fixed platelets by ristocetin, snake venom, or bovine factor VIII. These studies demonstrate that carbenicillin and penicillin G inhibit platelet function in vitro by impairing the interaction of several agonists with their specific receptors on the platelet surface membrane. If this were mechanism operative in vivo, it could account for the hemorrhagic as well as the potential antithrombotic effects of these antibiotics. PMID- 6243310 TI - Mechanisms of photodynamic inactivation of herpes simplex viruses: comparison between methylene blue, light plus electricity, and hematoporhyrin plus light. AB - Herpes simplex virus (HSV) types 1 and 2 have been inactivated in vitro using low concentrations of methylene blue (MB), light (lambda) plus electricity (E), or hematoporphyrin derivative (HPD) plus lambda. Both techniques introduce single strand interruptions into viral DNA, but do not make double strand ruptions into viral DNA, but do not make double strand breaks. MB, lambda plus E-treated virions adsorb normally to and penetrate susceptible cells, whereas HSV inactivated with HPC and light does not. This difference is emphasized by the induction of new viral and cell DNA synthesis after infection with MB, lambda plus E-treated virions, whereas only cell, DNA but no HSV DNA, is made subsequent to HPD and lambda exposure. These observations reflect disparate mechanisms of viral inactivation. A block(s) in viral maturation, subsequent to viral DNA synthesis, occurs as a result of treatment with MB, lambda and E, whereas HPD plus lambda-treated particles fail to enter a susceptible cell, and therefore do not initiate an infection. PMID- 6243311 TI - The impact of streptozotocin-induced diabetes mellitus on cyclic nucleotide regulation of skeletal muscle amino acid metabolism in the rat. AB - The impact of diabetes on cyclic nucleotide-associated mechanisms regulating skeletal muscle protein and amino acid metabolism was assessed using epitrochlaris preparations from streptozotocin-induced diabetic rats. 1 nM epinephrine inhibited alanine and glutamine release from control preparations, but no inhibition was observed from diabetic preparations with <0.1 mM. 10 nM epinephrine stimulated lactate production from control muscle but stimulation in diabetic preparations was observed only at 0.1 mM. Serotonin inhibited amino acid release and stimulated lactate production equally in control and diabetic muscle. 0.1 mM epinephrine increased cyclic (c)AMP levels by 360% in control muscles, but these levels were increased only 83% in diabetic muscle. Basal-, fluoride-, and serotonin-stimulated adenylyl cyclase activities were equal in membrane preparations of diabetic and control muscle, but epinephrine-stimulated adenylyl cyclase was reduced by 60% in diabetic muscle. Carbamylcholine stimulation of alanine and glutamine release was blunted in diabetic preparations. Carbamylcholine increased cGMP levels in control but not in diabetic muscle. In diabetic muscle, guanylyl cyclase activity was 65% of control and the stimulation of cyclase activity by sodium azide was less in diabetic than control preparations. Added cGMP stimulated alanine and glutamine release from control, but not from diabetic muscle. These data suggest a loss of adrenergic and cholinergic responsiveness in diabetic muscle. Because amino acid release also showed a decreased responsiveness to added cAMP and cGMP, the presence of other derangements in the mechanism(s) of cyclic nucleotide regulation of muscle amino acid metabolism also seems likely. PMID- 6243312 TI - Iodothyronine release from the perfused canine thyroid following cessation of stimulation: rapid decline of triiodothyronines in comparison with thyroxine. AB - The kinetics of thyroid secretion after termination of stimulation by 100 muU/ml bovine thyroid stimulating hormone (TSH) or 5 mM cyclic AMP (cAMP) were studied using perfused canine thyroid lobes. All experiments were performed as paired comparisons, one thyroid lobe acting as a control continuing to receive infusion of the stimulator. 2.5 h after termination of TSH infusion, the secretion of thyroxine (T(4)), 3,5,3'-triiodothyronine (T(3)), and 3,3',5'-triiodothyronine (rT(3)) was not significantly different from that of the control lobes. After cessation of cAMP infusion, the secretion of T(4) continued unaffected for approximately 40 min. Then a gradual decline in T(4) release occurred. The secretion of T(3) and rT(3) decreased somewhat earlier leading to a transient phase with increases in the T(4):T(3) and T(4):rT(3) ratios in the thyroid effluent. The persistently high secretion of iodothyronines despite cessation of TSH infusion is most likely the result of a continued stimulation by receptor bound TSH. Because the clearance of intracellular cAMP is rapid and the concentration of cAMP used for stimulation in these experiments only exceeded the concentration necessary for eliciting a secretory response modestly, it is reasonable to assume that stimulation of colloid droplet formation stopped shortly after termination of cAMP infusion. The bulk of iodothyronines secreted thereafter thus originated from continued hydrolysis of thyroglobulin engulfed by the follicular cells during the preceding cAMP infusion. The pattern of an earlier decline in secretion of T(3) and rT(3) than of T(4) from this intracellular pool of thyroglobulin points to a more rapid liberation of triiodothyronines than of thyroxine from thyroglobulin during intracellular hydrolysis. PMID- 6243314 TI - Human gingival collagenase in periodontal disease: the release of collagenase and the breakdown of endogenous collagen in gingival explants. AB - Collagen degradation in different stages of gingival inflammation was examined. Higher collagenolytic activity and nonspecific protease activity were found in the severely inflamed gingiva, as compared to mildly inflamed or healthy gingiva. This was shown by electrophoretic studies and measurement of peptide-bound hydroxyproline in the culture. PMID- 6243315 TI - Identification of collagenase in cultured blood mononuclear cells. AB - Mononuclear cells isolated from peripheral whole blood were fractionated by erythrocyte-rosetting into T cells and non-T cell subpopulations which were tested for collagenase-producing capacity. Mononuclear cells and purified T lymphocytes, as well as non-T (B) lymphocytes, produced collagenase during serum free culture. Removal of the macrophages from the non-T cells did not affect collagenase production by lymphocytes. PMID- 6243313 TI - Calcium-dependent action of osmolality on adenosine 3',5'-monophosphate accumulation in rat renal inner medulla: evidence for a relationship to calcium responsive arachidonate release and prostaglandin synthesis. AB - When urea and NaCl are employed as the major solutes of high osmolality buffers, the cyclic AMP (cAMP) content of oxygenated slices of rat renal inner medulla increases three- to fivefold as osmolality is decreased from 1,650 to 305 mosM. Incubation of slices in Ca2+-free media containing 2 mM EGTA largely abolished this action of osmolality on cAMP, whereas exclusion of Mg2+ or 5+ from the incubation media was without effect. Addition of Ca2+ to Ca2+-deprived inner medulla incubated at 750 mosM (175 mM Na+, 380 mM urea) significantly increased tissue cAMP and media prostaglandin (PG)E accumulation. Ca2+ also stimulated the release of 14C-fatty acid from Ca2+-deprived slices prelabeled with [14C]arachidonate, but not from those labeled with [14C]palmitate. The divalent cation ionophore A23187 enhanced the actions of Ca2+ to increase tissue cAMP, media PGE accumulation, and the release of [14C]-arachidonate from prelabeled inner medulla. By contrast, when slices were incubated at 1,650 mosM (365 mM Na+, 900 mM urea) in the presence or absence of A23187, all of these actions of Ca2+ were markedly suppressed or abolished. Addition of exogenous arachidonate increased tissue cAMP and media PGE at both 750 and 1,650 mosM, whereas palmitate and stearate had no effect on cAMP at either osmolality. The actions of Ca2+ and arachidonate to increase cAMP and PGE accumulation were abolished by the cyclo oxygenase inhibitors, indomethacin and meclofenamate. They were also abolished by exclusion of molecular O2, which serves as cosubstrate with arachidonate in prostaglandin synthesis. At maximally effective concentrations, exogenous PGE2 and arachidonate produced similar increases in inner medullary cAMP. The maximal effects of the two agents on cAMP were not additive, but were expressed in the absence of Ca2+ at both 750 and 1,650 mosM. However, in marked contrast to the O2-dependent action of arachidonate, PGE2 increased cAMP in the presence or absence of O2. Comparison of the separate actions of urea and NaCl indicated that suppression of Ca2+-responsive [14C]arachidonate release, PGE, and cAMP accumulation at 1,650 mosM reflected primarily an effect of urea, whereas hypertonic NaCl, mannitol, and sucrose alone stimulated inner medullary cAMP and PGE accumulation by a pathway which did not require extracellular Ca2+. Analogous to the actions of hypertonic urea, tetracaine and mepacrine inhibited the actions of Ca2+ plus A23187 to stimulate [14C]-arachidonate release, PGE, and cAMP accumulation. Inhibition of PGE and cAMP accumulation by tetracaine and mepacrine was also overcome by arachidonate. The results suggest that high osmolaity media with urea as a major solute reduces inner medullary cAMP content, at least in part, through effects on Ca2+-dependent prostaglandin synthesis. Inhibition of PGE synthesis, in turn, may be the result of osmotic suppression of Ca2+ dependent release of arachidonate, the availability of which is often rate limiting to prostaglandin generation. PMID- 6243316 TI - Isocyanato urethane methacrylates derived from hydroxyethyl methacrylate. AB - Isocyanato urethane methacrylates were synthesized from five diisocyanates and hydroxyethyl methacrylate. They may be homopolymerized or copolymerized with other methacrylates by the usual free radical methods of initiation and have potential as adhesion-promoting agents for dentin. PMID- 6243317 TI - Effect of fluoride on polymorphonuclear leukocyte myeloperoxidase. PMID- 6243318 TI - Characterization of autonomic receptors in isolated human parotid acinar cells. AB - Isolated human parotid acinar cells have been used for the in vitro characterization of the muscarinic cholinergic and alpha- and beta-adrenergic receptors of these cells. The agonist-antagonist interactions at the receptor level were studied, and the role of the receptor-activated cellular systems in the process of secretion was characterized. PMID- 6243319 TI - Multiple granular-cell tumors. AB - Granular-cell tumors are uncommon dermal tumors. Recent studies favor a neural, Schwann-cell derivation. Approximately 10% of cases have multiple lesions and a like percentage have tender lesions. We report a case of multipe (9) small, dermal tumors in which tenderness was associated with perineural infiltration. The need for therapy is discussed. PMID- 6243320 TI - Tachyphylaxis to inhaled isoproterenol and the effect of methylprednisolone in dogs. AB - Acute tachyphylaxis can be induced to inhaled isoproterenol (ISO) in anesthetized, closed-chested mongrel dogs. The responsiveness to ISO measured as the percent reduction in methacholine-induced bronchoconstriction was decreased significantly (p less than 0.01) after a 1-hr period of repeated ISO inhalations (ISO-loading). Intravenous administration of methylprednisolone (1 mg/kg) reversed the decrease in responsiveness to ISO. PMID- 6243321 TI - IgE antibodies in TDI workers. PMID- 6243322 TI - Cyclic nucleotide losses during tissue processing for immunohistochemistry. PMID- 6243323 TI - Reliability and specificity of membrane adenosine triphosphatase localizations. AB - The main development in ATPase cytochemistry in recent years is the development of three methodologically independent approaches to the localization of Na+, K+ ATPase. These methods in general support one another well and have led to significant insights into the mechanisms of bulk cation transport at several important sites. The area most in need of development is now the problem of specific localization of divalent ion-dependent ATPases at the plasma membrane. The value of the traditional Wachstein-Meisel methods appears to be very limited, and progress will depend on the introduction of more specific techniques. PMID- 6243324 TI - Autoradiographic localization of tritiated ouabain-sensitive sodium pump sites in ion transporting epithelia. AB - The freeze-dry autoradiographic method devised originally by Stirling (J Cell Biol 53:704, 1972) to localize Na+ pump sites with (3H)ouabain is reviewed. Biochemical, physiological, and autoradiographic data are discussed which establish that ouabain binding to intact tissue conforms to rigid criteria for high Na+ pump specificity. Among these are that glycoside binding exhibits saturation kinetics, ligand dependence, and close correlation with degrees of inhibition of Na+-K+-ATPase and Na+ transport. Moreover, localization of Na+ pump sites by this technique shows a cell and membrane specificity which mirrors that obtained by cytochemical and immunocytochemical methods. In addition to resolving cell-specific patterns of localization in heterogeneous tissues, the demonstration of Na+-K+-ATPase by these techniques indicates that Na+ pumps are distributed uniformly along plasmalemmal surfaces and are restricted to the basolateral interface in reabsorptive and secretory epithelia despite the opposing polarity of net transepithelial electrolyte transport. PMID- 6243325 TI - Cytochemical localization of acid phosphatase and trimetaphosphatase activities in exocrine acinar cells. AB - Acid phosphatase activity, a lysosomal marker, is commonly demonstrated using the Gomori technique with cytidine 5'-monophosphate or beta-glycerophosphate as substrate. Using this lead capture method on mouse and rat exorbital lacrimal, parotid, and pancreatic acinar cells, reaction product was localized in GERL, forming secretory granules, and secondary lysosomes. However, a different cytochemical localization was observed for inorganic trimetaphosphatase, another lysosomal enzyme. When the technique for trimetaphosphatase activity, a metal chelation method, was applied to exocrine acinar cells, reaction produce was conspicuously absent from GERL and forming secretory granules, but was present in secondary lysosomes, occasionally in Golgi saccules, and in previously unreported basal elongated lysosomes. The differences in the localization of the two enzymatic activities emphasizes the importance of employing more than one substrate where possible, and raises questions concerning the mechanism of delivery of acid hydrolases to secondary lysosomes. PMID- 6243326 TI - Comparison of media and methods for counting Clostridium perfringens in poultry meat and further-processed products. AB - A Most Probable Number (MPN) method involving Differential Reinforced Clostridial Medium followed by streaking on Willis & Hobbs medium was compared with direct plating of samples on Tryptose-Sulphite-Cycloserine agar without egg yolk, and two forms of Oleandomycin-Polymyxin-Sulphadiazine-Perfringens agar, one being prepared from a commercial, dehydrated product. With skin samples taken from chicken carcasses at different stages of processing, the three direct plating media gave similar counts of Cl. perfringens whereas results obtained with the MPN method were consistently lower. Although counts of Cl. perfringens from various further processed products were usually less than 10/g, the three plating media showed similar specificity for this organism. All media supported good growth of reference strains of Clostridium perfringens but it was found that physiologically similar species, including Cl. absonum, Cl. paraperfringens and Cl. perenne also grew uninhibited in these media and produced colonies identical with those of Cl. perfringens, thus indicating the need for confirmatory tests for Cl. perfringens when examining natural samples. PMID- 6243327 TI - Comparison of antibody responses and virus shedding following administration of trivalent oral poliomyelitis vaccines prepared either in monkey or human diploid cell substrates. AB - Nineteen (22.9%) of 83 sera collected before vaccination from adult volunteers aged 21-64 years were without neutralizing antibody to poliomyelitis at levels of 0.15 i.u./ml for types I and II and 0.1 i.u./ml for type III. Some correlations were found between the history of previous vaccination and the presence of antibody but these were not well defined. Vaccination with a single dose of trivalent oral polio vaccine elicited fourfold or greater antibody responses to one or more poliomyelitis types in 53 (63.9%) volunteers, the percentage antibody resposnes being inversely related to the titre of antibody present before vaccination. Types I, II or III poliomyelitis virus were recovered from 76.8% of faecal samples collected 1 week after vaccination. The percentage recovery progressively declined thereafter until virus was recovered from 10.5% of samples collected 6 weeks after vaccination. Type for type, the titres and percentages of antibody responses and virus shedding in faeces were similar following trivalent oral poliomyelitis vaccines whether prepared in monkey or human diploid cell substrates. Some change in reproductive capacity temperature (r.c.t./40) marker was found in faecal isolates from volunteers vaccinated with monkey kidney and human diploid grown vaccines but no change in 'd' marker was found. PMID- 6243328 TI - Inactivation of viruses in municipal effluent by chlorine. AB - The influence of pH and temperature on the efficiency of chlorine inactivation of two unrelated picornaviruses in a typical urban wastewater effluent was examined. Temperature, unlike pH, had relatively little effect on the rate of inactivation. The pH effect was complex and the two viruses differed. The f2 coliphage was more sensitive to chlorine at low pH, but at all values there was a threshold above which additional chlorine resulted in very rapid inactivation. The amount of chlorine required for this was less at low than at high pH, although at pH values above 7 the extent of inactivation was about the same. There was no apparent correlation between pH and rate of inactivation of poliovirus but there was a suggestion that at a pH close to the isoelectric point of the virus it was less sensitive to chlorination. PMID- 6243329 TI - Tumor cell lipid composition and sensitivity to humoral immune killing. I. Modification of cellular lipid and fatty acid content by metabolic inhibitors and hormones. PMID- 6243330 TI - Elicitation of anti-Sendai virus cytotoxic T lymphocytes by viral and H-2 antigens incorporated into the same lipid bilayer by membrane fusion and by reconstitution into liposomes. AB - We have investigated the minimal molecular requirements for elicitation of anti Sendai virus cytotoxic T lymphocytes (CTL), and the minimal molecular requirements for the recognition and lysis processes associated with anti-Sendai virus CTL-target cell interactions. This report demonstrates a) that the hemagglutinin-neuraminidase and/or fusion glycoproteins of Sendai virus can elicit anti-Sendai virus CTL and b) that these glycoproteins and H-2 antigens must be within the same membrane lipid bilayer for effective elicitation of anti Sendai-virus CTL and for effective recognition and lysis of target cells by anti Sendai virus CTL. PMID- 6243331 TI - The suppression of Epstein-Barr virus infection in vitro occurs after infection but before transformation of the cell. AB - It has been demonstrated that T cells from humans can suppress the transformation of EBV-infected B cells in vitro. In this paper, studies are presented on the mechanism of the suppression. The T cells do not act against the virus itself nor the infection process. They appear to suppress the outgrowth of B cells after they are infected but before they are transformed. The T cells are much less effective in suppressing the outgrowth of the B cells once the latter have transformed (24th post-infection). The significance of these observations to EBV infection and other forms of T cell-mediated anti-EBV immunity is discussed. PMID- 6243332 TI - T cell-mediated immunity to oncornavirus-induced tumors. I. Ly phenotype of precursor and effector cytolytic T lymphocytes. AB - Regression of tumor induced by murine sarcoma virus (MSV) is accompanied by the formation of specific cytolytic T lymphocytes (CTL). Selection of T-cells sets by Ly phenotype determination allows separation of T sets involved in the cytolytic reaction. After MSV inoculation we demonstrate that a) Ly123+ cells contain precursors of CTL, b) direct cytolysis is mainly mediated by Ly23 cells, 3) cytolytic memory is divisible into "early" memory, carried by Ly23 cells, and "late" memory, which reverts to an Ly123 precursor population, and d) Ly1 cells are required to induce anti-MSV antibody formation. PMID- 6243333 TI - T cell-mediated immunity to oncornavirus-induced tumors. II. Ability of different T cell sets to prevent tumor growth in vivo. AB - These studies demonstrate that two different types of protective immunologic reactions are generated in mice after inoculation with M.MSV. Type I protection, mediated by Ly1 cells, prevents MSV-induced sarcomas but has no effect on the growth of MLV+ lymphomas. This anti-MSV protection reflects induction of antivirion antibody and delayed type hypersensitivity reaction. Type II protection is mediated by Ly23 cells and prevents the growth of an MLV+ lymphoma, but has little or no protective effects against MSV-induced sarcomas. This "type II" reaction is directly related to CTL activity. The implications of these two protective reaction are discussed. PMID- 6243334 TI - An enzyme-linked immunoassay for the detection of antibodies to the mouse mammary tumor virus: application to human breast cancer. AB - An enzyme-linked immunoassay (ELISA) was developed, using the mouse mammary tumor virus (MMTV) fixed to wells of a microtiter plate, for the determination of antibodies to MMTV. The intensity of the final color change was dependent upon virus or viral antibody concentration. MMTV antibody was readily detectable in sera diluted as much as 1 : 2800. Fixed MMTV bound antibodies to an internal viral protein (p 28) as well as to viral envelope components (gp 52, gp 34), demonstrating that the virus was rendered permeable by our procedure. Applying this assay to human sera, significant differences (P less than 0.005) in IgG binding to MMTV were detected between sera of breast cancer patients, benign breast disease patients and healthy individuals. 26% of breast cancer-derived sera contained MMTV binding antibody; 10% of benign sera or 8% of normal sera were also positive. The reactivity of human IgG with MMTV was blocked by prior incubation of the virus with antisera to gp 34 or, to a lesser extent, with gp 52. The results demonstrate that MMTV antibodies can be quantitated by this simple, rapid and inexpensive procedure. PMID- 6243335 TI - Epidermal cyclic AMP is not decreased in psoriasis lesions. AB - The cyclic AMP level in epidermis of psoriatic patients was reappraised with a highly sensitive radioimmunoassay method in conjunction with an improved skin biopsy technique to avoid any artificial rise of cyclic AMP due to ischemia. Local intradermal injection before biopsy was avoided, since even saline injection caused a clear-cut ischemia effect. The results concur with our previous study: i.e., on a tissue dry weight or protein basis, the cyclic AMP level in the involved epidermis is 20% higher than that in the uninvolved spidermis of psoriatic patients, and on a DNA basis, there was no significant difference. The cyclic AMP level in normal epidermis from non-psoriatic subjects is the same as that in the uninvolved epidermis of psoriatic patients. Such characteristics in psoriatic lesions as the increased mitosis, incomplete, differentiation and increased glycogen content cannot be simply related to a cyclic AMP deficiency. PMID- 6243336 TI - Electron microscopic observations of concentric lamellar bodies within mesenchymal cells of anagen hair dermal papilla. AB - The presence of 2 forms of the concentric lamellar bodies was observed in the mesenchymal cells within dermal papilla of normal scalp anagen hairs. They are those composed of agranular membrane arrays in association with beta-glycogen particles (glycogen bodies) and those of smooth-surfaced endoplasmic reticulum (smooth-surfaced lamellar bodies). On rare occasions these 2 forms of the concentric lamellar bodies were simultaneously present within the same cells. Transitional forms between the smooth-surfaced lamellar bodies and phagosegresomal granules were also encountered. PMID- 6243337 TI - Reasons for optimism in childhood cancers. PMID- 6243338 TI - Attempts to induce interferon production by IdUrd induction and EBV superinfection in human lymphoma lines and their hybrids. AB - Inducers of the Epstein-Barr virus (EBV) cycle, 5-iodo-2-deoxyuridine (IdUrd), phorbol myristate acetate (TPA) and sodium butyrate were tested for their ability to induce EBV-determined antigens, early antigen (EA) and virus capsid antigen (VCA), and to stimulate interferon (IF) production in a variety of EBV-carrying lymphoid cell lines. IdUrd and TPA induced IF production to various extents in the different lines, whereas sodium butyrate did not. There was no relationship between induction of the EBV cycle and production of IF; the two appear to be independent characteristics. Superinfection with the transforming B95-8 virus substrain of EBV induced IF production, whereas superinfection with the abortively cytopathic, non-transforming P3HR-1 substrain had little or no IF inducing effect, in spite of its highly potent effect on virus antigen (particularly EA) synthesis. Analysis with specific antisera against IF showed that IF preparations produced by three different lymphoid cell lines in response to IdUrd treatment were composed of a mixture of the Le and F antigenic types, with the latter forming a minor species. In contrast, no detectable F interferon was present in spontaneously produced IF preparations from Namalwa cells, or after induction with B95-8 virus. PMID- 6243339 TI - Expression of the genome of defective interfering pseudorabies virions in the presence or absence of helper functions provided by standard virus. AB - The synthesis of virus RNA and proteins in cells infected with two populations of defective virions [Pr(1)53 and Pr(2)53] which vary in the overall composition of their DNA, but which share some structural and biological characteristics, have been examined. The experiments were done under two sets of conditions: (1) at high multiplicity of infection. In this case, practically all the cells in the cultures were co-infected with defective and infectious virions; (2) at low multiplicity of infection. In this case, 75% of the cells in the cultures were infected with defective virions only and 25% were co-infected with defective and infectious virions. The relative abundance of RNA classes complementary to different regions of the virus genomes that were synthesized under various conditions of infection were determined by the Southern (1975) technique; the synthesis of virus proteins was determined by polyacrylamide gel electrophoresis (PAGE). In cells co-infected with standard and defective virions, RNA complementary to the regions that are reiterated in the defective genomes is present in larger amounts than in cells infected with standard virions alone, indicating that the genomes of the defective virions are transcribed. Furthermore, the transcriptional controls that operate normally in the infected cells also operate in cells co-infected with standard and defective virions. The over-abundant accumulation of transcripts of some regions of the virus genome in cells co-infected with defective virions is not necessarily accompanied by an overproduction of some virus proteins. No difference in the PAGE profiles of the proteins synthesized was detected in cells co-infected with PR(1)53 and standard virions. However, cells co-infected with standard and Pr(2)53 overproduced three polypeptides. Transcription of the virus genome is detectable in cells infected with Pr(2)53 alone but not in cells infected with Pr(2)53 alone. Virus protein synthesis is also detectable under these conditions in Pr(2)-, but not in Pr(1) infected cells. Thus, despite the similarities in the biological characteristics of the two populations of defective virions described previously, similarities with respect to the expression of their genomes were not found. PMID- 6243340 TI - Persistent Theiler's murine encephalomyelitis virus infection in mice depends on plaque size. AB - Theiler's murine encephalomyelitis virus (TMEV) is an enteric pathogen of mice which causes acute and chronic neurological disorders in the natural host. When brain-derived stocks of TMEV isolates are adapted to cell culture they predominantly form either large or small plaques. In this study the type of central nervous system (CNS) infection (acute versus chronic) and the associated disease occurring in mice inoculated intracerebrally with large and small plaque strains of TMEV was investigated. Large and small plaque strains of TMEV were found to vary in virulence, type of neurological disease produced and ability to establish persistent CNS infection in mice. Two large plaque strains, GDVII and FA viruses, were highly virulent, produced acute encephalitis, but were cleared from the nervous systems of surviving animals. Therefore, it appears that these large plaque variants do not cause persistent CNS infection in mice. In contrast, five small plaque strains, DA, WW, TO4, Yale and BeAn8386 viruses, were relatively avirulent, usually produced no illness during the first month after inoculation, but readily established persistent CNS infection in mice. Persistently infected mice later developed demyelinating disease. Having identified strains of TMEV that differ regarding their ability to persist, we now hope to be able to exploit this difference in elucidating the basic mechanism(s) of TMEV persistence. PMID- 6243341 TI - Biochemical aspects of variation in foot-and-mouth disease virus. AB - The biochemical basis for variation in foot-and-mouth disease virus (FMDV) has been explored by analysis of the virus RNA and the virus-induced and structural proteins of three isolates of the virus. Two of the isolates were from serotype A and the third was from serotype O. Hybridization studies of the RNAs showed greater than 80% homology between the two type A viruses and about 65% homology between the two type A viruses and the virus of type O. The ribonuclease T1 maps of the three viruses gave distinct patterns typical of FMDV, but did not show that any two of the three viruses were more closely related. The virus-induced primary translation products, P88, P52 and P100 isolated from infected cells, were compared by tryptic peptide analysis. Combinations of 3H- and 14C-leucine labelled polypeptides were hydrolysed with trypsin and resolved on an ion exchange column. Much greater differences were found in P88 than in P52 or P100, indicating that the major variation occurs in the region of the genome coding for the structural proteins. Similar analysis of combinations of the structural proteins of the three viruses showed that there were differences in VP1, VP2 and VP3 and these results were supported by those obtained by PAGE analysis of the Staphylococcus aureus V8 protease cleavage products. PMID- 6243342 TI - Influence of input multiplicity of infection on the antiviral activity of interferon. AB - The antiviral activity of interferon was shown to be dependent on the input m.o.i. Cells could not be protected against the cytopathogenic effect of vaccinia, herpes, Echo or vesicular stomatitis virus at m.o.i. greater than 1. At a m.o.i. of less than or equal to 1, cells could be protected but the amount of interferon necessary to yield protection was inversely related to the m.o.i. When protection was afforded, it was only transient. The duration of the antiviral effect of interferon was also inversely related to the m.o.i. The dependence of the antiviral effect on the m.o.i. could not be explained by assuming the viruses to be mixtures of subtypes with different interferon sensitivity. Also, selection by interferon treatment of interferon-insensitive subtypes could not be shown. The greater antiviral effect of interferon at low m.o.i. was probably not caused by induction of interferon by the infecting virus. A direct inactivation by the virus of the antiviral effect of interferon could not be demonstrated. These results indicate that when interferon-treated cells are infected, they will not survive the infection. The only result of the interferon treatment will be to inhibit virus replication to some extent, leading only to a delay in cell death. PMID- 6243343 TI - A plaque assay for feline panleukopenia virus. AB - Plaque formation with representative strains of feline panleukopenia virus (FPV) has been obtained using a permanent line of feline kidney cells under agarose overlay. FPV-infected cells appear as white plaques after neutral red staining. Plaque size is determined by the extent of cell division in the infected monolayer. FPV assay by the plaque procedure is rapid and gives infectivity titres which exceed those determined by the common inclusion body and immunofluorescent assays of FPV by a factor of about 100 and 10, respectively. Moreover, the plaque assay offers an effective means for the quantification of neutralizing antibodies in feline sera as well as for the detection of heat stable substances in bovine sera which strongly interfere with replication of the virus. PMID- 6243344 TI - Persistent infection of a cell line of mouse origin after cell fusion by u.v. inactivated Sendai virus. AB - A cell line derived from Sendai virus-induced fusion of human adenocarcinoma and CBA mouse embryo cells had Sendai virus antigen (detected by immunofluorescence), together with bi-armed marker chromosomes, in 100% of the cells. After repeated passage, antigen-free cells carrying the same marker chromosomes appeared in the culture. Acrylamide gel analysis showed that all the Sendai virus antigens of antigen-positive cells were normal with the exception of the M protein. Antigen negative cells contained no virus proteins and could be superinfected with wild type virus, when all virus proteins appeared. PMID- 6243345 TI - DNA synthesis and multinucleation of mouse cells infected with SV40 in the presence of cytochalasin B. AB - DNA synthesis and nuclear division of mouse cells, BALB/3T3, infected with SV40 were studied and were compared with those of SV40-transformed mouse cells, mKS-A TU-7. Both SV40-infected and SV40-transformed cells behaved similarly in the presence of cytochalasin B and differently from normal noninfected cells, BALB/3T3. The chemical inhibited cytokinesis of all the cell groups but the nuclear division was inhibited only in the case of non-infected BALB/3T3. With SV40-infected BALB/3T3, multinucleation occurred with the increase of input m.o.i. by SV40. SV40-infected BALB/3T3 could enter the second S phase after release from double thymidine block in the presence of cytochalasin B, while BALB/3T3 could not enter the second S phase. In bi- or multinucleated cells of SV40-infected BALB/3T3, asynchrony of DNA synthesis among nuclei in a cell was evident, as was the case with mKS-A TU-7. PMID- 6243346 TI - Comparison of foldback sequences of herpes simplex virus types 1 and 2 DNA. AB - The DNAs of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) were separately denatured and allowed to renature briefly. The intrastand foldback structures that resulted from base pairing of inverted repeated sequences on otherwise single-stranded (ss) DNA were visualized in the electron microscope. The two genomes were found to contain similar size classes of small duplex stem DNA sequences. However, HSV-2 DNA appeared to possess an additional, larger size class of foldback structures not found on HSV-1 DNA. Both HSV DNAs were found to contain stem-plus-loop structures; the larger stem-plus-loop structures of the two genomes had similar stem lengths but dissimilar loop lengths. Thus, a comparison of the genomes of HSV-1 and HSV-2 showed that they possessed similar size classes of foldback sequences. PMID- 6243347 TI - Host antigens on avian oncoviruses: evidence for virus envelope antigens related to specific chicken erythrocyte membrane antigens. AB - Avian sarcoma viruses (ASV) of subgroups A to D, produced by chick embryo fibroblasts (CEF), are inactivated to a high degree by rabbit antisera to the membrane antigens of adult chicken and chick embryo erythrocytes, notably by antisera to an antigen of embryo erythrocytes, which is lost by adult erythrocytes and to another antigen specific to the latter erythrocytes. Contrary to virus inactivation by anti-CEF serum reported earlier, virus inactivation by the antisera to these two age-specific antigens does not require complement and is not paralleled by virolysis but by aggregation of virions. The two antigens related, or identical, to the age-specific erythrocyte membrane antigens thus shown to be present on the virus envelope do not pre-exist, or pre-exist only in a low amount, on the CEF membrane, since the virus-inactivating capacity of their antisera is not removed by absorption with CEF. Their appearance on the virus does not depend on cell transformation but only on infection, since both antigens are found on a ts ASV mutant produced at restrictive temperature by untransformed CEF and the virus-inactivating capacity of their antisera is removed by absorption with CEF infected with Rous-associated virus (RAV-1). These findings suggest that infection of CEF by avian oncoviruses may elicit the appearance, or enhance the expression at the cell surface of antigens characteristic of another cell type which may contribute to the formation of specific virus budding sites. PMID- 6243348 TI - Ultrastructural study of rotavirus replication in cultured cells. AB - A systematic ultrastructural analysis of the replication cycle of the simian rotavirus SA11 in permissive MA104 cells was performed under reproducible conditions. At 8 h p.i., small areas of viroplasm were seen adjacent to swollen vesicles of the rough endoplasmic reticulum (rer) containing a few 80 to 90 nm virus particles. At later times, the size and number of these inclusions increased and the rer contained large numbers of the 80 to 90 nm particles as well as 52 to 65 nm particles. Infected cells eventually lysed, releasing progeny virus. Other cytological alterations included virus particles sequestered in lysosome-like bodies, 15 to 20 nm tubular structures in the nucleus and/or cytoplasm, convoluted membranes within the rer, filament bundles associated with virus particles, and mitochondria containing 1 to 5 virus particles. In addition, SA11 replication was studied in several less permissive cell lines. The results were similar to those with MA104 cells except that a smaller percentage of the cells were productively infected. PMID- 6243349 TI - Cervical radiculomyelopathy caused by deposition of calcium pyrophosphate dihydrate crystals in the ligamenta flava. Case report. AB - A case of cervical radiculomyelopathy caused by multiple calcified nodules in the ligamenta flava is presented. Roentgenological examination of the cervical spine showed radiopaque nodular lesions, 7 x 7 x 5 mm in size, located in the paramedian portion of the posterior spinal canal. The nodules were removed surgically and they were confirmed to be calcifications of ligamenta flava. Microscopic examination of the nodules with the polarized light revealed extensive deposition of crystals. By x-ray diffraction study, the crystal was determined as calcium pyrophosphate dihydrate (CPPD: Ca2P2O7 . 2H2O). Although CPPD deposition in the cartilage has been known as pseudo-gout syndrome, deposition in the ligament has been reported only in a few cases. This is the first case with radiopaque calcified nodules in the ligamenta flava causing spinal cord compression, the composition of which proved to be CPPD. PMID- 6243350 TI - Interobserver variability in the interpretation of myocardial images with Tc-99m labeled diphosphonate and pyrophosphate. PMID- 6243351 TI - Re: Technetium-99m-pyrophosphate bone scans in hyperparathyroidism. PMID- 6243352 TI - A study of irradiated bone. Part II. changes in Tc-99m pyrophosphate bone imaging. AB - Quantitative Tc-99m pyrophosphate bone imaging was carried out in locally irradiated and control areas of New Zealand albino rabbits to determine the potential role of bone imaging in assessing the time course of radiation effects in bone and surrounding tissues. In vitro Tc-99m tissue assays, and serial radiographs. from the irradiated and contralateral limbs were obtained at regular intervals over the first 12 mo following irradiation for comparison with quantitative results from the camera studies. The autoradiographic localization of TcPPi was also studied in the x-irradiated and contralateral bones of the rabbits. The results show that TcPPi bone imaging is a sensitive in vivo indicator of early radiation effects upon vasculature and bone remodeling. The findings suggest that the quantitative bone-imaging technique may be useful in the evaluation of the effects of treatment modalities on the skeleton. PMID- 6243353 TI - The bifocal diverging collimator: a means of simultaneous biplane imaging of the heart during equilibrium radionuclide ventriculography. AB - We have constructed a bifocal diverging collimator (BDC), capable of simultaneously recording two views of the heart 50 degrees apart on each half of a standard imaging field. In this study, simultaneous two-view blood-pool scans using the BDC were compared with the same two separate views obtained using an all-purpose parallel-hole collimator (PHC), assessing left-ventricular ejection fraction and regional wall motion in 20 patients undergoing contrast left ventriculography (CV). Ejection fraction by BDC correlated closely with PHC (r = 0.94) and with CV (r = 0.88). Regional wall motion was scored qualitatively on a five-point scale from 3 (normal) to--1 (dyskinesis) with an 88% agreement between BDC and PHC and PHC for segment scores. The percentages for agreement between BDC and CV, and between PHC and CV, were identical, 79%. A single blood-pool scan acquisition using a new BDC provides information about global and regional left ventricular function in two planes, comparable with that of a PHC. PMID- 6243354 TI - Cellular response to respiratory viruses with particular reference to children with disorders of cell-mediated immunity. PMID- 6243355 TI - Vitamin D deficiency in a calcium-supplemented very low-birth-weight infant. PMID- 6243356 TI - Maturation of sympathetic neurotransmission in the rat heart. I. Ontogeny of the synaptic vesicle uptake mechanism and correlation with development of synaptic function. Effects of neonatal methadone administration on development of synaptic vesicles. PMID- 6243357 TI - Maturation of sympathetic neurotransmission in the rat heart. II. Enhanced development of presynaptic and postsynaptic components of noradrenergic synapses as a result of neonatal hyperthyroidism. PMID- 6243358 TI - Attenuation of the effect of punishment by thyrotropin-releasing hormone: comparisons with chlordiazepoxide. PMID- 6243359 TI - Kinetic studies on the interaction between botulinum toxin type A and the cholinergic neuromuscular junction. AB - Botulinum toxin-induced paralysis of neuromuscular transmission involves at least three steps. There is an initial binding step that is nontoxic, a translocation step that is nontoxic and a subsequent lytic step that produces blockade of transmission. In the absence of nerve stimulation, the binding step has a half time of similar to or approximately 12 min and a rate constant of similar to or approximately 0.058 . min-1. The binding step does not require calcium or nerve stimulation, and it has a low temperature dependence (Q10 similar to or approximately 1.6). In the absence of nerve stimulation, the translocation step has a half-time of similar to or approximately 4.9 min and a rate constant of similar to or approximately 0.141 . min-1. Translocation requires physiological concentrations of calcium. In the virtual absence of nerve stimulation (1 x 10( 2) Hz), the lytic step has a half-time of similar to or approximately 55 min and a rate constant of similar to or approximately 0.013 . min-1. The lytic step requires calcium, is facillitated by nerve stimulation and has a high temperature dependence by nerve stimulation and has a high temperature dependence (Q10 similar to or approximately 4.2). These data are used to propose a model for botulinum toxin interaction with the cholinergic nerve terminal. PMID- 6243360 TI - The effect of acute administration of an angiotensin converting enzyme inhibitor, captopril (SQ 14,225), on experimentally induced thirsts in rats. AB - In order to assess the role of angiotensin in the genesis of certain types of thirst, rats were administered the angiotensin converting enzyme inhibitor, captopril, in an attempt to block the increased water intake induced either by water deprivation or by i.p. administration of hypertonic saline. Water deprivation for 24 hr resulted in an increased water intake. Acute administration of 50 mg of captopril per kg i.p. at 45 or 60, but not at 15 or 30, min before return of water to the dehydrated rats significantly attenuated the drinking response. Rats administered 1% b.wt. i.p. of 0.25, 0.50, 0.75 or 1.00 M NaCl solution increased proportionately their water intake. Acute administration of 35 mg of captopril per kg b. wt. i.p. 15 min before loading with NaCl solution at any of the above concentrations had no effect on the increased thirst induced. These findings suggest that hypertonic saline-induced thirst is not mediated by angiotensin II receptors while water deprivation-induced thirst may involve both osmoreceptors and angiotensin II receptors. PMID- 6243361 TI - Inotropic actions of diacetyl monoxime in cat ventricular muscle. PMID- 6243362 TI - Sodium-potassium-activated adenosine triphosphatase activity as a measure of neuronal membrane characteristics in ethanol-tolerant mice. AB - (Na+-K+) activated adenosine triphosphatase of mouse synaptosomal membranes is inhibited by high concentrations of ethanol. When membranes were obtained from mice made tolerant to and physically dependent on ethanol by chronic exposure to an ethanol-containing liquid diet, the enzyme was resistant to the inhibitory effects of ethanol. Arrhenius plots of synaptosomal (Na+-K+) activated adenosine triphosphatase from control animals revealed that ethanol added in vitro lowered the transition temperature and altered the Arrhenius activation energies of this enzyme. Enzyme from ethanol-tolerant animals had a lower transition temperature than that from control animals, and ethanol added in vitro had no effect either on transition temperature or on activation energy of enzyme from ethanol-tolerant animals. The occurrence of lowered transition temperature and resistance to ethanol-induced alterations in transition temperature of the enzyme from ethanol tolerant animals most likely reflects changes in membrane composition. Changes in Arrhenius plots correlated in time with resistance to the inhibitory effects of ethanol on (Na+-K+) activated adenosine triphosphatase activity and the time course of disappearance of these effects was similar to that of the disappearance of functional tolerance to ethanol. The resistance to the effects of ethanol on membrane function may be related to ethanol tolerance evidenced by behavioral and physiological measurements. PMID- 6243363 TI - Strength and biocompatibility of polymethacrylate-silica composite dental implant materials. AB - A study was made of the strength properties of several composite dental implant materials composed of silica microspheres (6%, 24%, and 48% by weight) and PMMA. Prepared specimens of the materials were tested for compressive strength and tensile strength as a function of the curing methods. Compressive strength was reduced only slightly when the 6% mixture was used, as compared to 100% PMMA, but the compressive strengths of the 12% and 24% mixtures were reduced by approximately 30% when compared to 100% PMMA. The compressive strengths of these materials were reduced even further after curing in a microwave oven, and the tensile strengths decreased to a greater degree. The 6% mixture was reduced by 38% in the heat-cured specimens and was reduced by 27% in the microwave-cured specimens. Tooth replica implants were placed in baboons and the peri-implant tissues were studied histologically after 6 months. Inflammation was minimal. Peri-implant alveolar bone was viable and active, and both connective tissue and epithelial attachment to the implant surface was evident. PMID- 6243364 TI - Chlorination or reduced nicotinamide adenine dinucleotides by myeloperoxidase: a novel bactericidal mechanism. PMID- 6243365 TI - Nucleolar budding and formation of nuclear bodies in cultured thyroid cells stimulated by thyrotropin, dibutyryl cyclic AMP, and prostaglandin E2. PMID- 6243366 TI - A rapid method for visualization of single-stranded genomic RNAs of animal viruses. PMID- 6243367 TI - Nodular renal blastema, renal dysplasia and duplicated collecting systems. AB - The association of nodular renal blastema, renal dysplasia and duplicated collecting systems may represent more than a histopathological observation. Based on the "double hit" theory of oncogenesis, the appearance of this histologic pattern in kidneys with other developmental alterations may account for an increased risk of neoplasia. PMID- 6243368 TI - Pagetoid lesions associated with carcinoma of the bladder. AB - Three cases of pagetoid infiltrations by a transitional cell carcinoma are reported. The theories of histogenesis of extramammary Paget's disease are reviewed and discussed. Evidence from these cases suggests that the lesion develops because of the intraepithelial migration of cells. PMID- 6243369 TI - Genitourinary pathology in urban male Blacks of South Africa. AB - A 10-year study of genitourinary cancer in black urban male subjects in South Africa shows that all tumors of the genitourinary tract are rare except for nephroblastoma, which has a similar incidence to other population groups throughout the world. Carcinoma of the bladder is rare despite the endemicity of Bilharzia and, although carcinoma of the prostate is not infrequent in patients up to the seventh decade, after that the incidence is lower than in other population groups in which the rate increases steeply. In accord with other black groups throughout the world tumors of the testis are excessively rare. The comparative infrequency of carcinoma of the penis is ascribed to the relatively high rate of circumcision. PMID- 6243370 TI - Simple cysts of the kidney in children. AB - We discuss 5 children with simple renal cysts, 2 of whom were diagnosed initially as having a Wilms tumor or mesoblastic nephroma. The most common presenting feature of this lesion is a palpable mass, especially in the infant or younger child. In older children characteristic radiographic features can suggest a correct preoperative diagnosis. However, distinguishing a simple cyst and a solid tumor with necrotic degeneration may not be possible in the infant and younger child, and surgical exploration is indicated. PMID- 6243371 TI - Complex connections link brain, pituitary. PMID- 6243372 TI - Urine calcitonin levels in patients with bronchogenic carcinoma. AB - We demonstrated previously that high serum calcitonin values in bronchogenic carcinoma are useful clinically as a parameter of progress of the disease and response to therapy. After developing a procedure for the measurement of calcitonin in urine, we studied serum and urine levels in 41 patients with lung cancer, using both a carboxyl terminus and a midportion recognizing antiserum. In general, midportion antiserum was more useful. Urine calcitonin measurements alone were superior to serum in terms of numbers of patients having increased values with one or both antisera (76% vs 46%). When both antisera were used to assay both serum and urine, 90% of patients had abnormal values. Once a tissue diagnosis has been established, the radioimmunoassay of urinary calcitonin offers a new dimension to the utility of this hormone as a marker for bronchogenic carcinoma. PMID- 6243373 TI - Neurological dysfunction of the bladder in workers exposed to dimethylaminopropionitrile. AB - Neurogenic bladder dysfunction, characterized by hesitancy, need to strain, decreased stream, and increased duration of urination, developed in 104 (63%) of 166 employees working in the manufacture of polyurethane foam. Highest rates of illness (69%) occurred in production workers, and no illness occurred in office or warehouse workers. Onset of the epidemic coincided with introduction of a catalyst, dimethylaminopropionitrile (DMAPN), and monthly case incidence rates increased as DMAPN use increased. Outbreak ceased abruptly when DMAPN use was stopped. Of eight patients who underwent neurourologic testing during recovery, seven lacked either detrusor reflex or normal sensation of bladder filling; seven had a subclinical sensory abnormality; three had prolonged sacral-evoked responses; and two of these three had limb motor neuropathies. Dimethylaminopropionitrile is unique among known neurotoxins in producing urinary symptoms more frequently than limb nerve symptoms. PMID- 6243374 TI - An epidemic of urinary retention caused by dimethylaminopropionitrile. AB - An epidemic of urinary retention among workers in a polyurethane manufacturing plant was discovered in the spring of 1978. The most severely affected workers had neurogenic bladders confirmed by cystometrograms and mild sensory peripheral neuropathy. A survey of the plant disclosed increased incidence of urinary retention, muscle weakness, paresthesia, insomnia, and sexual dysfunction in exposed workers. A catalyst containing dimethylaminopropionitrile was identified as the probable causative agent, and after its removal no new cases occurred. PMID- 6243375 TI - Transformation of human leukocytes with Epstein-Barr virus after cellular exposure to chemical or physical mutagens. AB - Assays that quantitate leukocyte transformation were used to determine the effect of two chemical and two physical mutagens on Epstein-Barr virus (EBV)-induced transformation of human umbilical cord leukocytes (HUCL). After treatment of HUCL with methyl methanesulfonate (MMS). UV light, or X-rays, lymphocyte transformation by EBV displayed a typical "survival" curve usually associated with agent toxicity in dividing cell populations. Viral transformation showed increasing resistance to each of these agents if the lymphocytes were treated after virus infection. No enhancement of viral transformation was detected following MMS, X-ray, or UV treatment. In contrast, after sublethal doses of N methyl-N'-nitro-N-nitrosoguanidine (MNNG) were administered, HUCL were more readily transformed by exogenous EBV. Also, in direct contrast to the other mutagens tested, EBV-induced transformation became markedly more sensitive to MNNG when leukocytes were treated after virus infection. Neither chemicals nor radiation alone was capable of initiating HUCL transformation, nor could infectious EBV be routinely recovered from transformed HUCL treated with MNNG or radiation. These results suggest that MNNG enhanced transformation by predisposing leukocytes toward transformation during EBV infection. PMID- 6243376 TI - Common pathway for tumor cell uptake of gallium-67 and iron-59 via a transferrin receptor. AB - We studied the tumor uptake of [67Ga]citrate, [59Fe]citrate, and 125I-labeled transferrin (TF) by the in vitro growth form of EMT-6, a sarcoma-like mammary tumor of BALB/c mice. In analyzing the binding experiments, we developed a new mathematical model based on a formulation originally used to express the interaction of hormones with specific tissue receptors. The uptake of both carrier-free 67Ga and 59Fe by tumor cells was mediated by kinetically identical TF receptors. We also studied teric acid extracts of the stroma of EMT-6 tumors grown both in vivo and in vitro. Chromatography of these extracts on Sephacryl S 200 SF demonstrated that the cellular stroma contained specific TF-binding macromolecules. On the basis of these findings, we proposed the "transferrin receptor hypothesis" for the mechanism of 67Ga uptake by tumors. According to this view, a tumor-associated TF receptor is the functional unit responsible for the affinity of gallium for certain neoplasms. This receptor was also active in the uptake of iron by tumors. PMID- 6243377 TI - Inhibition of N-2-fluorenylacetamide-induced mammary tumorigenesis in rats by dietary polybrominated biphenyls. AB - Female SD rats were maintained for approximately 1 year on diets containing 300 ppm N-2-fluorenylacetamide (2-FAA), 50 ppm polybrominated biphenyls (PBB), or a combination of these chemicals (PBB + 2-FAA). Ingestion of 2-FAA significantly reduced the average survival time of the rats; this effect was virtually blocked by the simultaneous ingestion of PBB. Simultaneous ingestion of PBB also significantly reduced the overall incidence of 2-FAA-induced tumors during the examination period. The lower incidence of tumorigenesis was accompanied by an increase in the latency time for tumor induction; tumors were found in 100% of the animals given 2-FAA after 29 weeks of carcinogen ingestion, whereas only 50% of the PBB + 2-FAA-fed animals had tumors at the end of the experiment (53 wk of carcinogen ingestion). PBB significantly reduced the incidence of 2-FAA-induced tumors at nonhepatic locations (mammary gland and ear duct) but did not affect the incidence of hepatic tumors to a statistically significant extent. PBB ingestion did not significantly increase the incidence of tumors when compared with controls; 1 tumor was found in 1 of 12 rats fed 50 ppm PBB for 57 weeks, and no tumors were detected in 8 controls. PMID- 6243378 TI - Moloney murine sarcoma virus oncogenesis in T-lymphocyte-deprived mice: biologic and immunologic studies. PMID- 6243379 TI - Cytomegalovirus: development and progression of cytopathic effects in human cell culture. AB - Cytopathic effects of cytomegalovirus infection were studied in human cell cultures at various time intervals. Cells derived from human embryonic thyroid, skin-muscle, and lung were infected with five different strains of cytomegalovirus at multiplicities of infection of approximately 5 plaque forming units per cell. Under these conditions, cell rounding and early cytoplasmic inclusions were first apparent at 5 hours postinfection, whereas nuclear inclusions were first observed as a homogenous eosinophilic bead at 24 hours postinfection. Cytoplasmic and nuclear inclusions underwent extensive morphogenesis through 96 to 120 hours postinfection. Development of nuclear inclusions included the formation of distinctive beadlike subunits, which increased in size from their first appearance at 48 to 72 hours postinfection and underwent apparent contraction and breakup after 96 hours postinfection. While the cytopathology induced by various cytomegalovirus strains studied was generally similar, the kinetics of their development was different and independent of both the multiplicities of infection and the source of the fibroblastic cells. Such cytomegalovirus strain-associated differences in cytopathology could result from variances in biologic characteristics of the strains studied. PMID- 6243380 TI - Histoculture of human breast cancers. AB - Breast cancers from 53 patients were explanted in culture, and 39 with two-year or more follow-up and documentable tissue forms of cancer in culture (histoculture) are the subject of this report. Clinicopathologic findings have been correlated with dynamic aspects of the cancers in short-term histocultures, including cell cohesiveness, yield and survival time of the cancer cells in culture, emigration of macrophages from the explants, and the occurrence of special interactions of lymphocytes with cancer cells. The outstanding finding was the association of special lymphocyte-cancer cell interactions with a more favorable prognosis; six of seven patients (86%) with infiltrating ductal cancer showing lymphocyte congregation, emperiopolesis, or other special activity were tumor-free survivors. Additional findings were: 1) patients having four or fewer lymph nodes positive for cancer had a survival rate of 50%, but this fell to 20% when emigrating macrophages were not present in the cancer cultures; 2) eight of the 12 patients (67%) having discoid histoculture survival time of less than one week were tumor-free, as opposed to three of eight patients (27%) where tumor survival in vitro was greater than one week. The reverse was true for nondiscoid, poorly cohesive colonies of cancer; 3) the combination of tumor-negative lymph nodes and low in vitro cancer yield was associated with the best patient survival rate, 64%. However, the combination of negative nodes and high in vitro yield was linked to the worst patient survival (20%). Although the overall study does not permit definitive conclusions, there is an undeniable potential for the use of histocultures in the evaluation of human cancers. Expanded studies are warranted, including larger numbers of tumors and cultures, and longer patient follow-up periods. PMID- 6243381 TI - Comparison of lobectomy and wedge resection for carcinoma of the lung. AB - To evaluate comparatively lobectomy and wedge resection for carcinoma of the lung, we reviewed retrospectively 1,000 consecutive cases of lung cancer at a Veterans Administration Hospital. Of these cases, 252 were operable; 199 were resectable. Thirty-three patients underwent resection of their lesion as primary treatment. The indications for wedge resection were (1) insufficient pulmonary reserve, (2) resectable cerebral metastasis, (3) frozen-section results reportedly benign. One hundred twelve patients underwent standard lobectomy procedures. Of these patients, 40 were comparable to those patients undergoing wedge resection on the basis of age, histopathological examination, tumor size and location, and the presence of metastatic disease. One, 2, and 5 year survival rates were 85%, 58%, and 26%, respectively, for wedge resection and 75%, 55%, and 25%, respectively, for lobectomy. The operative mortality rate was 0% for wedge resection and 5% for lobectomy. These results indicate that for the patient with a peripheral lung carcinoma and no evidence of metastatic disease a wedge resection offers comparable survival rates with minimal risk of death. PMID- 6243382 TI - The adrenal cortex: physiological function and disease. PMID- 6243383 TI - The effect of elevated prolactin levels on plasma 1,25-dihydroxyvitamin D and intestinal absorption of calcium. AB - Because of evidence in experimental animals that prolactin stimulates production of 1,25-dihydroxyvitamin D, we evaluated several indices of calcium metabolism in patients who had hyperprolactinemia due to functioning pituitary adenomas and in normal age-matched controls. Plasma levels of 1,25-dihydroxyvitamin D in hyperprolactinemic patients were in the normal range (15 to 24 pg/ml versus 15 5o 75 pg/ml in controls). Intestinal absorption of calcium, plasma levels of immunoreactive parathyroid hormone, and serum values for calcium, phosphorus, and alkaline phosphatase were similar in patients and controls. We conclude that prolactin probably has no effect on plasma 1,25-dihydroxyvitamin D levels or calcium metabolism in man. PMID- 6243384 TI - [Viruses and gastroenteritis (author's transl)]. AB - In recent years it has been demonstrated that a group of viruses, Rotavirus for the children and Norwalk agent for adults, are a highly significant cause of acute gastroenteritis during the months of winter ("winter vomiting disease"). The Rotavirus was identified by Bishop et al. as a double-stranded RNA virus that can be isolate from faeces of children with acute gastroenteritis. Viral gastroenteritis is an autolimitate disease, although under certain conditions it may even lead to severe disease and death by profound dehydration and electrolyte imbalance; it is characterized by nausea, vomiting, diarrhea and others minor symptoms. This entity only affects children between 3 months and 6 years of age, with a little prevalence for the males. Breast-fed babies are commonly thought to be less likely than artificial-fed babies to suffer from infective diarrhea. Rotavirus infection is also known to occur in parents of infected children, but in this situation the symptoms are generally mild or absent and they needn't medical attention. The Rotavirus invade mainly the epithelium of the proximal intestine where they make a cytopatic and physiologic alteration (deficience in Na and K-ATPsa activity) that determines a disturbances of water and electrolyte transport across the epithelium thus contribute to the diarrhea. The best methods for detecting this type of viral gastroenteritis are electron microscopy and, specialy, the complement fixation test. In this moment we have not specific therapy for this new disease but because its epidemiological importance it must be in all clinical minds. PMID- 6243385 TI - Carcinoid apudoma arising in a glomus jugulare tumor: review of endocrine activity in glomus jugulare tumors. AB - Previous reports of endocrine activity of glomus jugulare tumors have been of pheochromocytomas but not carcinoid apudomas. This paper is to alert the otolaryngologist to the presence of carcinoid apudomas in glomus jugulare tumors. A patient with a long history of explosive diarrhea, facial flushing, and violent headaches, the symptom of carcinoid syndrome, was cured after removal of his large glomus jugulare tumor. The diagnosis of carcinoid syndrome is made with a good history and confirmed with a 24 hour urine collection for 5 Hydroxy indole acetic acid (5 Hiaa). a series of patients treated at the Johns Hopkins Hospital for glomus jugulare tumors is reviewed for the presence of endocrine activity and the literature on endocrine active glomus jugulare tumors is presented. Preoperative evaluation for the presence of both pheochromocytoma and carcinoid apudoma is recommended for all patients with glomus jugulare tumors. PMID- 6243386 TI - The neuroendocrine nature of the glomus cells: an experimental, ultrastructural, and histochemical tissue culture study. AB - Although the carotid body is an established chemoreceptor, there is considerable evidence also for its possessing a secretory function. While adrenergic neuroendocrine cells of neuroectodermal derviation exist in the central and autonomic nervous systems, the exact histogenesis of the mammalian carotid body is unsettled. The normal human carotid body and glomus jugulare tumor have been grown in tissue culture and their constituent cells have been observed to transform from epithelial to neuronoid appearing cells with extensive dendritic processes. This conversion has been further enhanced by the addition of nerve growth factor, a polypeptide specific for neural tissue. Electron microscopy confirmed that these culus cell. Histofluorescence revealed that these in vitro cells continued to synthesize and store biogenic monoamines in culture. Comparison of the morphologic, ultrastructural and histochemical features of the glomus cell with established neuroendocrine cells (central nervous system neurons, sympathetic ganglia cells, chromaffin cells) shows striking similarities. On the basis of these findings it is concluded that the glomus cell is a modified neuron of neural crest origin. The embryology, electron microscopy and histochemistry of the carotid body and related glomera and their tumors are reviewed. PMID- 6243387 TI - Skull base approach to glomus jugulare. AB - The skull base approach to the jugular bulb provides a better opportunity to preserve facial nerve function. Specifically, this applies to glomus jugulare tumors. Adequate exposure to remove even an extensive glomus jugulare tumor may be obtained by the skull base approach, working between the VIIth nerve left in its bony sheath and the lateral process of the first cervical vertebra. PMID- 6243388 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 10-1980. PMID- 6243389 TI - Malignant melanoma and small-cell carcinoma of the lung. PMID- 6243390 TI - Somatomedins (first of two parts). PMID- 6243391 TI - Sexual transmission of hepatitis A in homosexual men: incidence and mechanism. AB - We performed monthly examinations and serologic tests for antibody to hepatitis virus A (anti-HA) in a study of 57 heterosexual men and 102 homosexual men followed prospectively for a mean of 8.9 months and 6.1 months, respectively. The initial prevalence of anti-HA was 30 per cent in homosexual men and 12 per cent in heterosexual men P less than 0.01). The annual incidence of hepatitis A in susceptible (seronegative) homosexual men was 22 per cent, whereas no heterosexual men acquired hepatitis A. Diaries concerning sexual behavior kept by homosexual men showed that the acquisition of hepatitis A virus infection contact. Hepatitis A should be considered one of the enteric infections that appear to be sexually transmitted among homosexual men. PMID- 6243392 TI - Sustained remission of Nelson's syndrome after stopping cyproheptadine treatment. PMID- 6243393 TI - Pain, enkephalin and acupuncture. PMID- 6243394 TI - Transformation and tumorigenesis. PMID- 6243395 TI - Regulation of acetylcholinesterase appearance at neuromuscular junctions in vitro. AB - The appearance of acetylcholinesterase (AChE) at newly formed nerve-muscle synapses depends on synaptic transmission. Synapses form when cultures are grown in the presence of acetylcholine receptor antagonists, but AChE does not accumulate at these synapses. The important component of transmission seems to be muscle activity. Treatment with dibutyryl cyclic GMP mimics muscle activity, directly inducing synaptic AChE appearance. PMID- 6243396 TI - Interactions between the carbohydrate chains of hyaluronate and chondroitin sulphate. AB - Hyaluronic acid-derivatised beads spontaneously agglutinate with chondroitin sulphate-derivatised beads although neither bead type shows any self agglutination. The interaction between hyaluronate and chondroitin sulphate is specific for these two glycosaminoglycans and appears to occur between their carbohydrate chains. PMID- 6243397 TI - Met-enkephalin circulates in human plasma. AB - The physiological roles of Met-enkephalin and Leu-enkephalin are still unknown. They may act as neurotransmitters in the central and peripheral nervous systems. Met-enkephalin has been detected in several species in a variety of tissues including brain, spinal cord and gut using bioassays, opiate receptor assays and radioimmunoassays (RIA). It has also been detected in human gut immunocytochemically and in human brain and cerebrospinal fluid by opiate receptor assay and RIA. However, all reported assays show some degree of cross reaction with Leu-enkephalin and unequivocal differentiation between the two enkephalins and the larger endorphins has not always been possible. Thus the existence of Met-enkephalin in human tissues and fluids remains in doubt. Using a highly specific RIA, we have now obtained evidence that Met-enkephalin-like material circulates in the plasma of normal subjects and may be secreted by the adrenal gland. Chromatographically the material exists in plasma mainly as the intact pentapeptide and not as the biologically inactive degradation product Gly Gly-Phe-Met as would be expected from metabolic studies. PMID- 6243398 TI - GABA and picrotoxinin receptors in clonal nerve cells. PMID- 6243399 TI - Antibody response to Moloney type C virus-induced tumours. PMID- 6243400 TI - Noradrenaline and cyclic AMP--independent growth stimulation in newt limb blastemata. AB - Adult newts regenerate functional limbs after amputation. This process normally depends on the trophic influence of nerves on the regenerating limbs, particularly in the early stages before differentiation of the regeneration blastema, when it stimulates growth by maintaining high rates of macromolecular synthesis. The sequence of biochemical events involved is unknown, but it has been suggested that intracellular cyclic AMP may be a second messenger within the blastema. Many studies have indicated that the neural agent(s) involved might be protein. The recent finding that blastemata contain high levels of catecholamines, however, has implicated noradrenaline (NA) as the neurotrophic agent, and suggested that it works via stimulation of beta-adrenergic receptors on the blastemal cells, thereby raising the intracellular concentrations of cyclic AMP. To test this hypothesis we studied the ability of NA alone and in combination with alpha-and beta-adrenergic antagonists to increase cyclic AMP levels and to mimic the effects of nerves by maintaining high rates of protein synthesis and high mitotic indices (MI) in denervated blastemata in organ culture. We find that although NA raises cyclic AMP levels through a beta adrenergic effect, it does not maintain high rates of protein synthesis or high MI in cultured blastemata. It is unlikely therefore, that this hypothesis applies. PMID- 6243401 TI - Coding potential and regulatory signals of the polyoma virus genome. AB - The complete DNA sequence of the A2 strain of polyoma virus has been determined. It consists of 5,292 base pairs. The sequence is analysed in terms of its coding potential and sites of possible functional significance or structural interest. The polyoma virus genome is compared with those of related tumour viruses, simian virus 40 and BK virus. PMID- 6243402 TI - Different components of black widow spider venom mediate transmitter release at vertebrate and lobster neuromuscular junctions. PMID- 6243403 TI - Modulation of nicotinic receptors by opiate receptor agonists in cultured adrenal chromaffin cells. AB - Morphological, physiological and pharmacological evidence indicates that opioid peptides, which in the brain are located intraneurally, may function as neurotransmitters. Similar evidence is not yet available for the opioid peptides that are stored in chromaffin cells of adrenal medulla and in axon terminals located in adrenal medulla and sympathetic ganglia. The present report contributes evidence suggesting that the opioid peptides which are stored in the axon terminals of the splanchnic nerves located in adrenal medulla may function as neuromodulators of the acetylcholine receptors located on chromaffin cells that are involved in catecholamine release. We support this functional role of the opioid peptides by showing that primary cultures of chromaffin cells of bovine medulla contain opiate receptors. When these receptors are occupied by specific agonists, the number of nicotinic receptors and the amount of catecholamine released by maximal doses of nicotine are reduced. Thus, like in other neuronal systems also in adrenal medulla, the action of opioid peptides is inhibitory. The specificity of this action is in part supported by the inability of opiate receptor agonists to reduce the Ca2+-dependent release of catecholamines elicited by K+ ions. PMID- 6243404 TI - Induction of interferon in AKR mice by murine leukaemia viruses. AB - A high percentage of AKR mice develop spontaneous leukaemia which has shown to be associated with the early expression of ecotropic murine leukaemia virus (MuLV) and the subsequent expression of xenotropic as well as polytropic MuLVs. Generally, mice infected with any one of several groups of viruses, including MuLVs, have been shown to produce interferon (IF). However, we report here that AKR mice produce no IF, despite that fact that infectious, endogenous MuLV is expressed in these mice from birth. PMID- 6243405 TI - Serum 1,25-dihydroxycholecalciferol in anephric, haemodialyzed and kidney transplanted patients. Effect of vitamin D3 supplement. AB - The serum levels of 25-hydroxycholecalciferol (25-OHD3) and 1,25 dihydroxycholecalciferol[1,25-(OH)2D3] were measured simultaneously in nephrectomized patients on maintenance haemodialysis, in haemodialyzed patients with preserved kidneys who were receiving different vitamin D supplement, and in patients who had undergone renal transplantation. The results indicate that the production of 1,25-(OH)2D3 can be stimulated in patients with minimal residual renal excretory function by increasing the serum levels of 25-OHD3. Successful renal transplantation was followed by a rise in serum 1,25-(OH)2D3 concentrations. PMID- 6243406 TI - Hypothalamic-pituitary evaluation in patients with galactorrhea-amenorrhea and hyperprolactinemia. AB - Twenty-two women with galactorrhea and/or amenorrhea were evaluated. Thyroxine (T4), thyroid-stimulating hormone (TSH), and visual fields were normal. Hyperprolactinemia (22 to 440 ng/ml) was present in 19 patients. Evidence of tumor was found in 73.7% of the woemn, whereas 26.3% were classified as functional. Three patients with empty sella syndrome showed normal prolactin levels (12.2 to 18.5 ng/ml). There was a significant negative correlation between prolactin levels and follicle-stimulating hormone (FSH) (P less than 0.05), but not between prolactin and luteinizing hormone (LH) levels. Hypocyloidal polytomography was better than plain x-ray films in detecting early prolactin secreting pituitary tumors (14 patients). Pituitary testing using an insulin tolerance test showed a statistically significant difference in human growth hormone (hGH) reserve between tumor and functional groups (P less than 0.0005), and none for the cortisol response. The 17-hydroxycorticoid response to metyrapone was impaired in the tumor patients (group 1). Serum prolactin levels showed various degrees of suppression with L-dopa (9.3 to 98.8%), with no significant difference between the various groups. PMID- 6243407 TI - Cerebral metastatic choriocarcinoma: intensive therapy and prognosis. AB - Choriocarcinoma is known to be sensitive to chemotherapy. Remission rates of 70% are reported for patients with metastatic disease. The Southeastern Regional Trophoblastic Disease Center of Duke University has reviewed its experience with the treatment of cerebral metastases from choriocarcinoma. Fourteen patients were identified as having cerebral metastases from a group of more than 500 patients with gestational trophoblastic disease (GTD) other than primary hydatidiform mole. The remission rate of 50% (7/14) was achieved by vigorous, multiagent chemotherapy and combined cerebral irradiation therapy. This series of patients is reviewed with regard to diagnosis, details of multiagent chemotherapy with cerebral irradiation, complications, and survival. The key factors for successful outcome seem to be early diagnosis and vigorous therapy. PMID- 6243408 TI - Krukenberg carcinoma of the ovary with bone marrow involvement. Report of 2 cases and review of the literature. AB - Krukenberg carcinoma of the ovary accounts for 1 to 3% of ovarian neoplasms. The nature and behavior of this particularly virulent tumor remain unclear. In this paper, 2 cases are presented of Krukenberg carcinoma metastatic from the gastrointestinal tract; in both bone marrow involvement was detected early in the course of the disease. The histopathology of the tumor is described. A comprehensive review of the literature in English is provided, and therapeutic approaches to the disease are discussed. PMID- 6243409 TI - Clinicopathologic review of 118 granulosa and 82 theca cell tumors. AB - The clinical course and histologic features of 118 granulosa cell tumors and 82 theca cell tumors were reviewed. Although the 2 cell types are related, important differences exist in their behavior. Theca cell tumors (TCTs) are virtually benign, while granulosa cell tumors (GCTs) exhibit less malignant activity than most ovarian carcinomas. Characteristically detected at an early stage, GCTs may recur locally years after the initial diagnosis. Survival figures depend on tumor stage. Recurrence of GCTs is associated with a high mortality rate. The cornerstone of treatment is total abdominal hysterectomy and bilateral salpingo oophorectomy, regardless of age. Adjuvant radiation or chemotherapy may be helpful when lesions are higher than stage lai. Therapy for recurrence usually requires operative excision combined with radiation, chemotherapy, or both. PMID- 6243410 TI - Mucinous carcinoma of the endometrium. AB - Three cases of mucinous carcinoma of the endometrium are presented. These can be distinguished anatomically from endocervical carcinomas and histochemically from endometrial clear cell carcinomas. Clinically these patients do not differ significantly from others with endometrial carcinoma, but the tumors produce large amounts of extracellular and intracellular neutral and acid mucopolysaccharides. Mucinous carcinoma is regarded as a morphologic variant of endometrial carcinoma. PMID- 6243411 TI - Nongonococcal bacterial septic arthritis. An update on diagnosis and management. AB - Nongonococcal septic arthritis, particularly if caused by Staphylococcus aureus or Gram-negative bacilli, presents major dilemmas to the primary care physician. Patients with this disorder require prolonged regimens of parenteral antibiotics in high doses and intensive serial radiographic investigation for coexistent osteomyelitis. For patients with pyoarthrosis caused by Gram-negative bacilli, use of combination synergistic chemotherapy is recommended. PMID- 6243412 TI - Role of interferon in the antiviral state elicited by selected interferon inducers. PMID- 6243413 TI - Phosphonoacetic acid induced persistence of varicella-zoster virus in cell culture. PMID- 6243414 TI - Photodynamic inactivation of herpes simplex virus by hematoporphyrin derivative and light. PMID- 6243415 TI - Effect of n-butanol on Na+, K+-ATPase. AB - The effect of n-butanol on the activity of Na+, K+-ATPase has been found different at different temperatures. Below the phase-transition temperature, n butanol has a stimulating effect provided the concentration is not higher than 0.3 M. But if the activity is determined above the phase-transition temperature, n-butanol has an inhibitory effect. The p-nitrophenyl phosphatase activity has been found to be inhibited by n-butanol even at comparatively low temperatures. This is in accord with the finding that the Arrhenius plot for p-nitrophenyl phosphatase did not show any break. It is suggested that at lower temperatures the conformational change involved in the transport of Na+, K+ ions may be the rate-limiting factor in the overall reaction, and n-butanol may be used as a probe for perturbation of the membrane to elucidate the mechanism of Na+, K+ ATPase. PMID- 6243416 TI - Selective inhibition of glycoprotein and membrane protein of vesicular stomatitis virus from interferon-treated cells. AB - A 200-fold inhibition in the titer of infectious vesicular stomatitis virus (VSV) was produced in cultures of Ly cells treated with 30 reference units of interferon per milliliter. Virus particle production, as measured by VSV particle associated transcriptase, or nucleocapsid protein was inhibited by a maximum of tenfold. The glycoprotein and membrane protein content was reduced in VSV derived from interferon-treated cells. Thus interferon-treated cells may have produced VSV particles with low infectivity, which may be related to the reduced amount of glycoprotein incorporated into such particles. These findings resemble those reported in interferon-treated cells infected with murine leukemia viruses. PMID- 6243417 TI - Postsynaptic transmission block can cause terminal sprouting of a motor nerve. AB - Sprouting of mouse soleus motor nerve terminals can be evoked by daily intramuscular injections of purified alpha-bungarotoxin. This finding supports the hypothesis that an important stimulus to terminal sprouting in partial denervation and presynaptic nerve blockade is a product of inactive muscle fibers. PMID- 6243418 TI - Amino acid acylation: a mechanism of nitrogen excretion in inborn errors of urea synthesis. AB - Treatment of a patient deficient in carbamyl phosphate synthetase with benzoate or phenylacetic acid resulted in an increase in urinary nitrogen, which could be accounted for by the respective amino acid acylation product, hippurate or phenylacetylgultamine. Benzoate treatment of four hyperammonemic comatose patients led to clinical improvement and a return of plasma ammonium levels toward normal. PMID- 6243419 TI - Cell growth with trans fatty acids is affected by adenosine 3',5'-monophosphate and membrane fluidity. AB - Two positional isomers (9 and 11) of trans octadecenoates did not support growth on glucose of an Escherichia coli mutant that requires unsaturated fatty acids. However, the trans fatty acids provided sufficient fluidity to produce much higher cell yields when the concentration of adenosine 3',5'-monophosphate was raised. The effectiveness of the trans acids rose from 0 to 1 cell per femtomole to 15 to 20 cells per femtomole as the concentration of adenosine 3',5' monophosphate was increased. The corresponding cis positional isomers supported high yields (35 to 40 cells per femtomole) independent of supplementation. The enhanced growth with adenosine 3',5'-monophosphate supplementation is not due to an increased uptake and incorporation of the trans isomers relative to the cis isomers, since the 9-trans isomer was incorporated more rapidly than the 9-cis isomer into the membrane phospholipids under all growth conditions and represented 21 +/- 2 mole percent of the acids. The finding that cells growing with trans fatty acid isomers have a higher requirement for adenosine 3',5' monophosphate may indicate that some fatty acids can alter the metabolic regulation normally exerted by the cyclic nucleotide. PMID- 6243420 TI - DNA gyrase and the supercoiling of DNA. AB - Negative supercoiling of bacterial DNA by DNA gyrase influences all metabolic processes involving DNA and is essential for replication. Gyrase supercoils DNA by a mechanism called sign inversion, whereby a positive supercoil is directly inverted to a negative one by passing a DNA segment through a transient double strand break. Reversal of this scheme relaxes DNA, and this mechanism also accounts for the ability of gyrase to catenate and uncatenate DNA rings. Each round of supercoiling is driven by a conformational change induced by adenosine triphosphate (ATP) binding: ATP hydrolysis permits fresh cycles. The inhibition of gyrase by two classes of antimicrobials reflects its composition from two reversibly associated subunits. The A subunit is particularly associated with the concerted breakage-and-rejoining of DNA and the B subunit mediates energy transduction. Gyrase is a prototype for a growing class of prokaryotic and eukaryotic topoisomerases that interconvert complex forms by way of transient double-strand breaks. PMID- 6243421 TI - Testing for cancer risk. PMID- 6243422 TI - Genes and cancer: the story of Wilms tumor. PMID- 6243423 TI - [Slow IBR infections: a critical approach]. PMID- 6243424 TI - Egg production in relation to the results of a long term serological survey of 73 flocks of fowl. AB - Seventy-three flocks of fowl were tested at regular intervals for the presence of precipitins to fowl adenovirus (AV) and infectious bronchitis virus (IBV), haemaggluinating inhibiting antibodies to BC in 14 virus, and of agglutinins to Mycoplasma gallisepticum (M.g.) and Mycoplasma synoviae (M.s.). In all the eight flocks affected with Egg Drop Syndrome (EDS '76), egg production problems were associated with increasing numbers of BC14 virus reactors and AV reactors. In flocks showing production problems other than EDS'73 without any apparent cause, the average percentage of AV reactors increased significantly after the rearing period; this was not true of IBV reactors. BC14 reactors were either absent or present only once, in small numbers and with low titres, during the test period. The average percentage of AV reactors did not increase after the rearing period either in normally producing flocks or in flocks with production problems for which other diseases or dietary errors plausibly accounted for these problems. All this suggests a pathogenic role of AV in production problems. One can conclude from the high percentage of reactors in all groups of flocks that subclinical IBV infections are common. The percentage of IBV reactors during the laying period of flocks with EDS'76 was significantly higher than that of normally producing flocks. It is therefore suggested that subclinical IBV infection could be among the factors causing stress, acting as a trigger for EDS'76. All M.g.-infected flocks showed production problems; M.s. infections could not be related to egg production disturbances. PMID- 6243425 TI - Investigations on live vaccines against infectious bursal disease of chicks. AB - Four live virus vaccines against Infectious Bursal Disease (IBD) were studied with regard to their safety, immune response and applicability. None of the vaccines caused clinical symptoms or had an adverse impact on bodyweight. Differences between these vaccines were observed in their effect on the Bursa/Bodyweight Ratio and the severity of the microscopical lesions of the bursa Fabricii. The immunosuppressive effect of IBD vaccination at one day of age on the response to Newcastle disease vaccine applied was rather low. Three of the four vaccines induced antibodies associated with protection against challenge. Vaccination of SPF rearing chickens by drinking water at an age of 15 weeks produced an antibody response (Agar Gel Precipitin Test) whereas at 15 weeks produced an antibody response (Agar Gel Precipitin Test) whereas at an age of 23, 32 and 60 weeks it did not. Chickens of all age groups responded serologically to an intramuscular vaccination. A correlation was found between the immunological response and the effect of the vaccines on the bursa Fabricii. PMID- 6243426 TI - Phenotypic heterogeneity among temperature-sensitive mutants of Rous sarcoma virus. Studies with inhibitors of protein synthesis. PMID- 6243427 TI - Effect of sulfhydryl reagents on the infectivity of vesicular stomatitis virus. PMID- 6243428 TI - Assembly of membrane glycoproteins studied by phenotypic mixing between mutants of vesicular stomatitis virus and retroviruses. PMID- 6243429 TI - Physical mapping of herpes simplex virus type 1 ts mutants by marker rescue: correlation of the physical and genetic maps. PMID- 6243430 TI - Studies on the activity of DNase associated with the replication of the Epstein Barr virus. PMID- 6243431 TI - Transformation parameters of chicken embryo fibroblasts infected with the ts34 mutant of avian erythroblastosis virus. PMID- 6243432 TI - Induction of viral DNA synthesis in clonal derivatives of a permissive cell line transformed by a temperature-sensitive polyoma virus. PMID- 6243433 TI - Kinetics and location of poliovirus macromolecular synthesis in correlation to virus-induced cytopathology. PMID- 6243434 TI - Generation of defective interfering particles in picornaviruses. PMID- 6243435 TI - The genomic RNA of avian reticuloendotheliosis virus REV. PMID- 6243437 TI - Cell-free translation of avian erythroblastosis virus RNA yields two specific and distinct proteins with molecular weights of 75,000 and 40,000. PMID- 6243436 TI - Hematopoietic cell transformation by reticuloendotheliosis virus: characterization of the genetic defect. PMID- 6243438 TI - In vitro translation of avian erythroblastosis virus RNA: identification of two major polypeptides. PMID- 6243439 TI - The expression of SV40 large T-antigen in embryonal carcinoma--SV40 transformed somatic cell hybrids. PMID- 6243440 TI - Tubular carcinoma of the breast: association with multicentricity, bilaterality, and family history of mammary carcinoma. AB - Seventeen tubular carcinomas occurred among 211 consecutive mastectomies (7.6%). The relative frequencies of multicentric involvement in the ipsilateral breast (56%), history of bilateral mammary cancer (38%) (P less than .01), and family history of mammary cancer in a first-degree relative (40%) (P less than .05) were all significantly greater in patients with tubular carcinomas than among patients with other carcinomas studied in a review of serial subgross examined mastectomy specimens. Patients with tubular carcinomas also tended to be somewhat younger (56 vs. 59 years) than those with other forms of mammary cancer. These features suggest that tubular carcinoma may be a histologic marker for a subpopulation of patients with mammary carcinomas strongly associated with multicentricity, bilaterality, and familial history of mammary carcinoma. PMID- 6243441 TI - Signet-ring cell carcinoma of the breast: a clinicopathologic study of 24 cases. AB - Twenty-four cases of signet-ring cell carcinoma of the breast are presented. These represented 4.5% of 535 cases of surgically treated breast cancer at Indiana University Medical Center. Twelve cases were associated with ductal carcinoma, nine with lobular carcinoma, one with colloid carcinoma, and four were pure signet-ring cell carcinoma. The mortality rate, incidence of axillary lymph nodal metastases, and number of involved lymph nodes were greater in cases of signet-ring cell carcinoma than with other forms of mammary carcinomas without signet-ring cells. It is proposed that signet-ring cell carcinoma can manifest as a pure lesion or as a variant of ductal, lobular, or colloid carcinoma, and that it is an aggressive histologic variant of mammary carcinoma. PMID- 6243442 TI - A study of variability in cytologic diagnoses based on pulmonary aspiration specimens. AB - Reproducibility of cytologic diagnoses of malignancy and accuracy and variability of diagnoses of malignant cell types were assessed in a study of pulmonary aspirates from 100 patients. Original cytologic diagnoses were positive for 60 of the 80 patients who had malignancy (true-positive rate 75%). No false-positive diagnosis was made. Original cytologic diagnoses were negative for 15 of the remaining 20 patients (true-negative rate 75%). In "blindly" reviewing the slides, the pathologist who had made the original diagnoses (Observer A) and another pathologist (Observer B) confirmed the 60 original positive diagnoses. Observer A added four cases, Observer B 11 cases to the positive category. Cell types of original positive cytologic diagnoses and those of subsequent histologic diagnoses agreed for 23 of 33 malignancies (70%). Although two observers increased the proportion of positive cytologic diagnoses, the percentages of agreement with respect to histologic malignant cell types remained similar. For cytologic specimens, intraobserver agreement as to malignant cell types was 83% (50 of 60); interobserver agreement was 80% (48 of 60). PMID- 6243443 TI - Supranormal 25-hydroxyvitamin D and subnormal 1,25-dihydroxyvitamin D: their role in X-linked hypophosphatemic rickets. AB - Serum 25-hydroxyvitamin D (25-OH-D) and 1,25-dihydroxyvitamin D (1,25-(OH)2D) and bone mineral content by the photon-absorption technique were determined in eight patients with X-linked hypophosphatemic rickets treated for at least 24 months with oral sodium phosphate and high-dosage ergocalciferol (vitamin D2). Mean 25 OH-D2 level was 129.5 +/- 67.5 ng/mL (mean +/- SD); the level of 25-OH-D3 was 10.5 +/- 5.8 ng/mL. These values were significantly higher than in normal subjects (total 25-OH-D mean of 27 +/- 10 ng/mL). Serum 1,25-(OH)2D was 16.9 +/- 8.5 pg/mL (mean +/- SD) in the eight patients, significantly lower than 47 +/- 16 pg/mL in 27 age-matched controls. Values indicative of significant demineralization were found in seven of the eight phsophate-treated patients, who had no radiologic evidence of rickets. These results suggest that any theory of the pathogenesis of this disorder must account for inappropriate renal vitamin D metabolism and for renal hyperphosphaturia. The failure of high-dosage oral phosphate and ergocalciferol to fully correct demineralization may suggest a role for calcitriol (1,25-(OH)2D3) as a therapeutic agent. PMID- 6243444 TI - Treatment of metastatic gestational trophoblastic neoplasms. A brief review of developments in the years 1968 to 1978. PMID- 6243445 TI - Acute pulmonary edema associated with molar pregnancies: a high-risk factor for development of persistent trophoblastic disease. PMID- 6243446 TI - Keratopathy after oral administration of tilorone hydrochloride. AB - Two patients given tilorone HCl orally for varying periods of time had clinical and histopathologic ocular changes. Retrospective study of 14 cancer patients who were taking tilorone HCl orally revealed that three patients had similar ophthalmic findings accompanied by the appearance of blue halos around pinpoint light sources. Examination revealed a diffuse clouding of the epithelium sometimes associated with subepithelial infiltrates. Abnormalities seen histologically included cloudy swelling of the epithelium and cytoplasmic inclusions. By electron microscopy these were found to be myelinoid bodies. Gas chromatography and mass spectrophotometry showed that tilorone HCl was present in the cornea and conjuctiva. Visual acuity was not affected and these changes were slowly reversible with the cessation of therapy. Biomicroscopic and conjunctival cytologic examination may serve to indicate the drug's storage and potential damage in the body. PMID- 6243447 TI - Electric currents, bone remodeling, and orthodontic tooth movement. I. The effect of electric currents on periodontal cyclic nucleotides. AB - Osteogenesis has been found to occur in response to the application of electric currents to bone. The objective of this experiment was to study the effects of D.C. electric currents on periodontal tissues in cats. Cyclic nucleotides, compounds known to be involved in cellular activation, were studied by immunohistochemistry in the involved tissues. Three groups of three young adult cats each were treated for 1, 3, and 7 days, respectively, by a device delivering 15 microamperes of direct current to bone osteoblasts and PDL cells stained intensely for cAMP and cGMP were observed adjacent to the cathode and anode, and bone apposition was found near the cathode. These results suggest that electric stimulation enhances cellular enzymatic phosphorylation activities in periodontal tissues and may be a potent tool in accelerating alveolar bone turnover. PMID- 6243448 TI - Electric currents, bone remodeling, and orthodontic tooth movement. II. Increase in rate of tooth movement and periodontal cyclic nucleotide levels by combined force and electric current. AB - Piezoelectric currents in mechanically stressed bone were implicated in the activation of bone cells. The objectives of this experiment were to determine the usefulness of exogenous electric currents in accelerating orthodontic tooth movement and to study the effect of electric-orthodontic treatment on periodontal cyclic nucleotides. Maxillary canines were tipped in five cats by 80 g force. Two groups of five cats each were treated by an electric-orthodontic procedure to one maxillary canine for 7 and 14 days, respectively. Teeth treated by force and electricity moved significantly faster than those treated by force alone. Enhanced bone resorption was observed near the anode (PDL compression site), while bone formation was pronounced near the cathode (PDL tension site). Staining for cyclic nucleotides was increased when electric stimulation was added to the mechanical force. These results suggest that orthodontic tooth movement may be accelerated by the use of locally applied electric currents. PMID- 6243449 TI - Do tricyclic antidepressants enhance adrenergic transmission? An update. PMID- 6243450 TI - Altered distribution of pulmonary ventilation and blood flow following induction of inhalation anesthesia. PMID- 6243451 TI - Immunoglobulin E and A levels in atopic and anaphylactic children. AB - Seventy-six children between 18 months and 12 years of age were included in this study. Sixty-one were atopic and 15 had anaphylaxis due to bee stings or drugs. Immunoglobulins: A, G. M and E were determined and evaluated with respect to age and diagnosis. IgA levels were lower in atopic children between six and ten years than in normals. IgE levels were high in both atopic and anaphylactic patients but higher in the atopic than in the anaphylactic group. The results are discussed, focusing on the question of basic immunologic impairment in allergy. PMID- 6243452 TI - Studies with a hydrophobic, spin-labeled virucidal agent. AB - A spin-labeled virucidal agent was synthesized, purified, and tested for its activity against the enveloped bacterial virus phi6 and herpes simplex virus. This compound, designated BPN, inactivated greater than 99% of phi6 and herpes simplex virus in vitro at concentrations as low as 0.1 mM. Detailed studies were carried out on the mechanism of inactivation of phi6 by BPN. These studies revealed that treatment of phi6 by BPN specifically removes a single envelope protein that is considered to be responsible for adsorption of the virus to the host cell. Related experiments with the phi6 host, Pseudomonas phaseolicola strain HB10Y, showed that this organism is insensitive to the effects of BPN. The basis for the differential sensitivity of phi6 to BPN, in comparison to the host cell, was investigated by electron spin resonance techniques. It was found that, for phi6, HB10Y, and their extracted phospholipids, BPN is localized in the hydrocarbon zones of the membrane bilayer. However, in the case of phi6, the rotational mobility of BPN is much reduced in comparison to that in HB10Y and the phospholipid preparations. Furthermore, an Arrhenius plot of rotational correlation time (tau(c)) showed a marked discontinuity in slope at 31 degrees C in the case of phi6, but not for the other samples studied. This suggests a strong interaction between the phi6 envelope proteins and the lipid domains in which BPN is localized. Calculations based on the known lipid and protein composition of phi6 indicate that there is an absence of "free-lipid" pools in the viral envelope. It is suggested that BPN localizes in free-lipid pools of cell membranes, where its presence is of little or no consequence, but that in phi6 the BPN perturbs the hydrophobic interactions between phospholipids and proteins in the envelope. PMID- 6243453 TI - Aminoglycoside-resistant mutation of Pseudomonas aeruginosa defective in cytochrome c552 and nitrate reductase. AB - A gentamicin-resistant mutant of Pseudomonas aeruginosa PAO503 was selected after ethyl methane sulfonate mutagenesis. The strain, P. aeruginosa PAO2401 had increased resistance to all aminoglycosides tested but exhibited no change for other antibiotics. The mutation designated aglA (aminoglycoside resistance) was 50% cotransducible with the 8-min ilvB,C marker on the P. aeruginosa chromosome. It showed a marked reduction in cytochrome c(552) and nitrate reductase (Nar) and a change in terminal oxidase activity. Cytochrome c(552) is a component of the P. aeruginosa Nar. No changes in succinate and reduced nicotinamide adenine dinucleotide dehydrogenases, ubiquinone content, Mg(2+)/Ca(2+) membrane adenosine triphosphatase, and energy coupling of electron transport to adenosine 5' triphosphate synthesis were detected. Transport of gentamicin and dihydrostreptomycin was impaired in PAO2401, but transport of proline, arginine, glutamine, glucose or the polyamine spermidine was not reduced. Ribosomes of PAO2401, and PAO503 bound dihydrostreptomycin equally well, and cell extracts did not inactivate gentamicin or dihydrostreptomycin. Strain PAO2401 is resistant to gentamicin and dihydrostreptomycin because of impaired transport of these compounds. The transport studies indicate a selective coupling of dihydrostreptomycin and gentamicin transport with terminal electron transport. This conclusion was supported by results from another mutant (PAO417-T2) with increased Nar activity, enhanced dihydrostreptomycin and gentamicin transport and a reduction in resistance to these drugs. These results are discussed in relation to a refined model for aminoglycoside transport and briefly relative to plasmid mediated aminoglycoside resistance. PMID- 6243454 TI - Transplantation of insulinoma into the diabetic Syrian hamster. AB - Syrian hamsters were rendered diabetic with intraperitoneal streptozotocin and were maintained in the diabetic state for a minimum of 14 days. A hamster islet cell tumor was transplanted subcutaneously with a prompt return of water intake (38 +/- 9.1 ml/day to 7.1 +/- 2.2 ml/day, mean +/- SD), urine glucose (4.8 +/- 0.84 g/day to less than 250 mg/day), urine output (37.4 +/- 10.9 ml/day to 7.6 +/ 2.1 ml/day), blood glucose (297 +/- 31.9 mg/dl to 87.6 +/- 28 mg/dl), and weight gain (1.0 to 0.8 g/day) to normal control levels. Histologic examination of the engrafted tumors revealed a well encapsulated tumor with no evidence of metastatic disease. The transplanted insulinomas maintained well differentiated histologic features without evidence of necrosis. Immunopathologic studies failed to reveal any evidence of either humoral or cell mediated immunity directed toward the allograft. Each animal was successfully transplanted with a 1 mm tumor explant. A single rodent tumor donor provided adequate material for engraftment for five recipients. The transplanted insulinomas maintained full functional and enzymatic capabilities. Similar studies utilizing the hamster insulinoma engrafted into the athymic nude mouse showed amelioration of the same diabetic symptomatology. Many of the technical difficulties encountered with whole organ and isolated islet transplantation encourages development of a more practical model. These experimental results suggest an alternative method for supplying the diabetic with an endogenous insulin source. PMID- 6243455 TI - Clinically occult breast cancer. Multicentricity and implications for treatment. AB - Two hundred thirty-two biopsies have been performed for nonpalpable mammary lesions, detectable by mammography, but not clinically apparent. Sixty-two malignancies were demonstrated within this group, including thirty invasive ductal cancers, seven minimally invasive ductal cancers, 20 noninvasive ductal cancers, and five lobular carcinomas-in situ. When mastectomy specimens were examined for evidence of multifocal cancer in quadrants other than that in which the primary was located, 39.6% of the breasts examined demonstrated evidence of multifocal cancer ductal or lobular, invasive or non-invasive. These findings suggest that any therapeutic procedure for invasive or noninvasive ductal cancer which does not include total mastectomy may leave behind foci of cancer which may be a threat to the patient. PMID- 6243456 TI - Echocardiographic diagnosis of a right ventricular metastatic tumor. AB - Clinical and echocardiographic studies were done in a patient with a secondary right ventricular tumor. Stationary cardiac tumors produce differential diagnostic problems not associated with mobile cardiac tumors. In spite of limitations of specificity, positive diagnostic features do exist. This report emphasizes the usefulness as well as technical difficulties in assessing the presence of a secondary right ventricular tumor echocardiographically. PMID- 6243457 TI - Zoster immune globulin. PMID- 6243458 TI - The vitamin craze. PMID- 6243459 TI - The glucagonoma syndrome. Report of a case. AB - A 73-year-old man had diabetes mellitus, diarrhea, weight loss, and a rash of several years' duration. The rash, termed necrolytic migratory erythema, was the most characteristic feature and eventually suggested the diagnosis of a glucagon secreting tumor of the pancreas. Diabetic ketoacidosis also developed in our patient, a previously unrecognized occurrence with this syndrome. PMID- 6243460 TI - Electromyographic feedback: effect on voluntary muscle contractions in paretic subjects. AB - To evaluate the efficacy and function of emg feedback (emgFB) in muscle reeducation, skeletal muscle contractions with and without emgFB were compared under controlled experimental conditions in human subjects with paresis due to brain damage (n=6) or peripheral nervous system damage (n=6). Each subject was instructed to produce 12 sustained 30-second contractions of a muscle below functional strength, 6 contractions in each of 2 sessions. EmgFB was provided in half the trials, alternating with nonfeedback trials. Emg activity during each trial was quantitified and the data analyzed statistically. By the 2nd session, emg activity was significantly greater during voluntary muscle contractions attempted with emgFB for both subject categories. This differential developed over the 1st 10 seconds of the muscle contraction and remained relatively constant until the end of the 30-second trial period. Response to emgFB was not closely linked to type of injury, duration of injury, or age. These results indicated a substantial and positive response to such feedback. PMID- 6243461 TI - Collagenase in human cornea: immunologic localization. AB - Collagenase has been localized in human corneas using immunocytochemical techniques employing a specific antiserum to human skin collagenase. The enzyme was found in vivo in ulcerating corneas, whereas in corneas obtained from a variety of nonulcerative conditions, no immunologic evidence of the enzyme was seen. Corneal collagenase was present only in the stromal portion of the cornea, suggesting that cells from this tissue are the source of the enzyme. The localization of collagenase to the corneal stroma was reproduced by placing either ulcerating or nonulcerating corneas in tissue culture, indicating that the organ culture system may represent a model that duplicates some conditions present in corneal disease. PMID- 6243462 TI - Primary tumors of the external and middle ear. Benign and malignant glandular neoplasms. AB - Glandular neoplasms represented 14% of primary tumors of the external and middle ear at the University of Minnesota. Although the collective term "ceruminoma" has been used in the past, four distinctive histopathologic patterns were recognized among our 12 cases: adenoma (four cases), pleomorphic adenoma (one case), adenoid cystic carcinoma (two cases) and adenocarcinoma (five cases). The prognosis correlated with these subgroups. A thorough review of the English literature also tended to support the rationale for the subclassification of so-called ceruminomas. The prevailing histogenetic view is that these tumors are derived from the modified apocrine glands of the auditory canal, the ceruminous glands. In some instances, these tumors may originate from ectopic salivary gland tissue. PMID- 6243463 TI - Pathologic quiz case 1. PMID- 6243464 TI - Effect of naloxone and morphine on guinea pig tonic immobility. PMID- 6243465 TI - Studies of serum immunoglobulin binding to synovial fibroblast cell cultures from patients with rheumatoid arthritis. AB - Using a sensitive 125I-protein A (PrA) binding assay to detect cell surface IgG, we have studied seven different synovial fibroblast cell cultures from patients with rheumatoid arthritis (RA). When these cultures were incubated in the presence of serum from 18 autologous and allogeneic RA patients (all seropositive), we were unable to detect significant IgG binding. Since IgM rheumatoid factor (RF) can block PrA binding, sera were absorbed with aggregated IgG to remove RF without affecting the results. Similar studies on three cell lines with seven rheumatoid sera were performed by antibody-dependent cell mediated cytotoxicity. No significant cytotoxicity was observed. Since antibodies to collagen are present in rheumatoid sera, several cultures were incubated with ascorbic acid (12.5 microgram/ml) to optimize synthesis of cell surface collagen. These culture conditions did not affect serum immunoglobulin binding by the 125I PrA assay. Thus, we can find no evidence for a direct humoral immune mediation of synovial proliferation in rheumatoid arthritis. These data do not support the hypothesis that the inflammatory process within the synovium of RA patients is an immunologic response to a fibroblast-associated antigen in the synovial membrane. PMID- 6243466 TI - Failure to detect type-C virus p30-related antigen in systemic lupus erythematosus: false-positive reaction due to protease activity. PMID- 6243467 TI - [Cytomegalic inclusion disease. Report of a case in a newborn]. AB - A clinical case of this disease in a newborn is reported. The clinical signs and laboratory results were typical and were confirmed by pathological studies. The modern literature stresses the high frequency of this disease, specially in the U.S.A. and England, where reports reach 4% in pregnant women and 1% of newborns with cytomegalic inclusion disease. We do not know its frequency in Mexico. PMID- 6243468 TI - [Subtotal pancreatectomy as treatment of acute hypoglycemia of the newborn]. AB - The most frequent causes of hypoglycemia in the newborn are reviewed and the pertinent diagnosis procedures in order to establish its etiology are discussed apropose of a case of nesidioblastosis. Physiological considerations are made around the pancreatic insulin response to two stimuli: I.V. glucose and glucagon, used in the present case. The indication of subtotal pancreatectomy in the cases of severe hypoglycemia is re-examined. PMID- 6243469 TI - 5'-Nucleotide phosphodiesterase: features of the substrate binding site as deduced from specificity and kinetics of some novel substrates. AB - Phosphonate monoesters and phosphate diesters with systematically varied substituents and leaving groups were synthesized and tested as substrates for homogeneous 5'-nucleotide phosphodiesterase from bovine intestine. The enzyme was shown to hydrolyze phosphorothioate and phosphonoamidate compounds but at significantly lower rates than comparable oxy compounds. The effects of bulk and structure of the ester or phosphonate substituents were also investigated. Dibenzyl phosphate, an ester of an aliphatic alcohol, was a poor substrate. The enzyme did not hydrolyze aliphatic monoesters of phosphonates, regardless of bulk. Kinetic parameters of several nitrophenyl phosphonomonoesters and phosphodiesters are presented. The results suggest that synthetic nonnucleotide substrates can bind in two different modes, only one of which is productive. Incidence of nonproductive binding, with consequent kinetic effects, is increased by increasing the symmetry of the substrates. PMID- 6243471 TI - Synthesis of dicytidylyl-(3'-5')-1,2-di(adenosin-N6-yl)ethane and dicytidylyl-(3' 5')-1,4-di(adenosin-N6-yl)butane: covalently joined terminals of two transfer ribonucleic acids and their behavior toward snake venom phosphodiesterase. AB - The chemical synthesis of the tital bridged trinucleoside diphosphates 3e and 3f along with the corresponding dinucleoside phosphates 3c and 3d is described. Bridged nucleosides 3a and 3b gave on treatment with triethyl orthoformate in the presence of p-toluenesulfonic acid in dimethylformamide the cyclic orthoesters 2a and 2b. Condensation of 2a and 2b with N,2',5'-O-triacetylcytidine 3'-phosphate (1) using dicyclohexylcarbodiimide in pyridine afforded after deblocking and chromatographic separation products 3c-f. The latter were readily degraded with pancreatic RNase, but 3c and 3e were completely resistant toward snake venom phosphodiesterase whereas 3d and 3f were digested to the extent of 65 and 43%, respectively. The major product of degradation of 3f with phosphodiesterase was compound 3d resulting from the combined action of phosphodiesterase and contaminating phosphomonoesterase. The results are explained in terms of stacking of terminal bridge nucleoside units in 3c-f. The implications of these findings for the function of snake venom phosphodiesterase are discussed. PMID- 6243470 TI - Adenosine cyclic 3',5'-monophosphate dependent protein kinase: active site directed inhibition by Cibacron Blue F3GA. AB - Cibacron Blue F3GA, the polycyclic blue chromophore of Blue Dextran 2000, inhibits the catalytic subunit of bovine brain protein kinase. The rate of inactivation exhibits a hyperbolic dependence on the dye concentration. This suggests that an enzyme-dye complex forms prior to inactivation. Protein and peptide substrates or MgATP protects the enzyme against dye inactivation. Kinetic measurements show that the dissociation constant is approximately 100 micro M and the maximal rate of inactivation is 0.13 min-1 at 22 degree C. Inactivation is temperature and time dependent. Exhaustive dialysis, gel filtration, or the addition of substrate fails to reactivate inhibited enzyme. The failure to reverse the inhibition suggests that the dye forms a covalent complex with the enzyme. Denaturation by sodium dodecyl sulfate also fails to dissociate the dye from enzyme. The hyperbolic kinetics, moreover, suggest that the dye functions as an active site directed reagent. The holoenzyme is resistant to Cibacron Blue inactivation. Addition of cAMP converts the enzyme to a form susceptible to inhibition. In agreement with our previous studies, these results also suggest that the regulatory subunit shields, either physically or functionally, the active site of the catalytic subunit. PMID- 6243472 TI - Urea denaturation of horse heart ferricytochrome c. Equilibrium studies and characterization of intermediate forms. PMID- 6243473 TI - Fidelity of fractionated deoxyribonucleic acid polymerases from human placenta. PMID- 6243474 TI - A reaction involving protein sulfhydryl groups, a bound spin-label, and K3Fe(CN)6 as a probe of sulfhydryl proximity in myosin. PMID- 6243475 TI - Influence of the mouse major histocompatibility complex, H-2, on liver adenylate cyclase activity and on glucagon binding to liver cell membranes. AB - The major histocompatibility complex of mice, the H-2 complex, regulates the steady-state level of adenosine cyclic 3',5'-monophosphate (cAMP) in liver. This effect of H-2 may be due to an effect on hormone binding to receptors. Here we show that liver membranes from animals of different H-2 types differ in their sensitivity to glucagon stimulation of adenylate cyclase and in the affinity of their receptors for glucagon. No H-2-associated differences are seen in basal, NaF-stimulated, or GMP-PNP-stimulated adenylate cyclase. PMID- 6243476 TI - Effect of chemical perturbation with NaSCN on receptor-estradiol interaction. A new exchange assay at low temperature. AB - When 0.5 M sodium thiocyanate is added to uterine cytosol previously labeled with excess [3H]-17 beta-estradiol, no change can be detected in the steady-state cytosol concentration of [3H]estradiol-receptor complex for at least 20 h at 4 degrees C. However, the rate of exchange of bound estradiol in the presence of NaSCN was found to be substantially higher than that in the absence of the chaotropic salt. In the presence of NaSCN, the dissociation rate of the complex increases about 10-fold (K-1 SCN = 1.10 x 10(-2) min-1 vs. K-1 = 1.07 X 10 ( 3)min-1) while the rate of association increases about 2-fold (K1 SCN = 1.2 X 10(7) min-1M-1 vs.K1= 7.4 X 10(6) min-1 M-1). The Kd changes 6.4-fold (Kd SCN = 9 X 10(-10) M vs. Kd = 1.4 x 10(-10 M) with no decrease in the number of binding sites as shown by Scatchard plots of saturation experiments. This effect of NaSCN can be exploited to assay preformed estrogen-receptor complex by exchange with [3H]estradiol at low temperature. When the sample containing preformed complex is incubated overnight (16 h) at 4 degrees C with excess [3H]estradiol in the presence of 0.5 M NaSCN, there is a quantitative exchange of nonlabeled for estradiol without loss of binding sites. Hormonal steroids other than estrogens do not interfere, and the exchange estradiol is bound with high affinity. Precision, accuracy, and linearity of the method are highly satisfactory. PMID- 6243477 TI - Stereochemical course of a phosphokinase using a chiral [18O]phosphorothioate. Comparison with the transfer of a chiral [16O,17O,18O]phosphoryl group. AB - Synthetic adenosine 5'-O-[3-18O,3-thio]triphosphate having the R configuration at the gamma-phosphorus has been used as a substrate in the reaction catalyzed by glycerol kinase. The product sn-glycerol 3-[18O]phosphorothioate has been isolated, and the configuration at phosphorus has been determined by ring closure to the two diastereoisomeric cyclic 2,3-phosphorothioates of sn-glycerol and analysis of the 18O content of each diastereoisomer. The structural identity of these diastereoisomers has been determined by correlation with one of the corresponding diastereoisomers of the cyclic 2,3-phosphorothioate of D-glycerate, whose crystal structure is reported here. From these experiments it is evident that glyc:rol kinase catalyzes the transfer of a thiophosphoryl group with inversion of the configuration at phosphorus, in gratifying agreement with the result from the transfer of a chiral [16O,17O,18O]phosphoryl group [Blattler, W. A., & Knowles, J. R. (1979) J. Am. Chem. Soc. 101, 510]. PMID- 6243478 TI - Structural mapping of rabbit muscle phosphofructokinase. Distance between the adenosine cyclic 3',5'-phosphate binding site and a reactive sulfhydryl group. AB - The cAMP binding site of rabbit muscle phosphofructokinase has been labeled with the fluorescent molecule 5'-(p-fluorosulfonylbenzoyl)-2-aza-1,N6-ethenoadenosine. The most reactive sulfhydry- group of this modified enzyme, which is catalytically active, has been labeled with 7-chloro-4-nitrobenzo-2-oxa-1,3 diazole and with N-]4-(dimethylamino)-3,5-dinitrophenyl]maleimide. The calculated distances between the cAMP binding site and the most reactive sulfhydryl group, as determined by resonance energy transfer measurements, are 31 and 26 A, respectively, for the two sulfhydryl group labels. Both steady-state and fluorescent -ifetime techniques were used to measure the energy transfer efficiencies in 50 mM potassium phosphate (pH 8.0) and 1 mM ethylenediaminetetraacetic acid, and a value of 2/3 was assumed for the donor acceptor orientation factor. If the difference in calculated distances is attributed to a difference in the orientation factor for the two donor-acceptor ,airs, the actual distance between the cAMP ligand binding site and the most reactive sulfhydryl group on phosphofructokinase is shown to be 28 +/- 6 A. PMID- 6243479 TI - Interaction of opioid peptides with model membranes. A carbon-13 nuclear magnetic study of enkephalin binding to phosphatidylserine. AB - The binding of enkephalin to phosphatidylserine has been studied, by using 13C NMR, as a model for interactions with components of biological receptors. Chemical shifts, line widths and spin-lattice relaxation times were measured for peptides enriched to 90% in 13C. The pKa values of the terminal amino and carboxyl groups were determined from the pH dependence of the 13C chemical shifts. Interaction of (2-[2-13C]glycine) methionine-enkephalin, (3-[2-13C] glycine)methionine-enkaphalin, and (3-[2-13C]glycine)methionine-enkephalinamide with phosphatidylserine (PS) was studied as a function of pH. Salt and morphine antagonism to binding was manifest. Binding was shown to be pH dependent, exhibiting a maximum under slightly acidic conditions. Whereas the -NH3+ group of enkephalin is essential for binding, the data suggest that neither the tyrosyl hydroxyl group nor the COO- group is involved. Binding affects the 13C spin lattice relaxation times most strongly; the chemical shifts and line widths of the 13C-enriched material show little perturbation in the presence of PS. The internal flexibility of the peptides is decreased, on binding to model membranes, by 1 order of magnitude. Dissociation constants have been measured as 4 X 10(-1) M and 2.6 X 10(-3) M for enkephalin and enkephalinamide, at pH 6.3 and 6.4, respectively. PMID- 6243480 TI - Enzyme asymmetry in hepatic microsomal vesicles. Criteria for localization of lumenal enzymes with proteases. AB - Chymotrypsin inactivation of lysophosphatidic acid acyltransferase activity in detergent-disrupted rat liver microsomes, but not in intact microsomes, falsely indicated a lumenal location for the enzyme. Inhibition by several other proteases in the absence of detergent showed that lysophosphatidic acid acyltransferase activity is located on the cytoplasmic surface of microsomes. Chymotrypsin inactivation did not occur in vesicles disrupted by nitrogen cavitation unless deoxycholate was present, suggesting that deoxycholate exposes a cryptic chymotrypsin cleavage site. Criteria for localization of lumenal microsomal enzymes should include studies using several proteases and/or employ more than one method of microsomal disruption. PMID- 6243481 TI - Spontaneous and detergent-induced vesiculation of thymocyte plasma membranes. AB - An analog of lysophosphatidylcholine (1-dodecyl-propanediol-3-phosphocholine) which does not impair membrane-bound enzymes was used for the induction of shedding of membrane vesicles from intact calf thymocytes. Without liberation of intracellular enzymes such as lactate dehydrogenase (EC 1.1.1.27) the shedded membranes contained 15--25% of the total activity of the plasma membrane enzymes alkaline phosphatase (EC 3.1.3.1), nucleotide pyrophosphatase (EC 3.1.4.1) and gamma-glutamyl transferase (EC 2.3.2.2). Membrane-free supernatants only exhibited trace activities of these enzymes. Without further purification, the specific enzyme activities in shedded membranes were of the same order of magnitude as in purified plasma membranes prepared after nitrogen cavitation of thymocytes. Small amounts of membrane vesicles which showed a different composition could be removed without detergent. These membranes exhibited a 3 fold lower specific activity of the gamma-glutamyl transferase while that of the alkaline phosphatase and nucleotide pyrophosphatase was similar as in detergent induced membrane vesicles. Distinct differences also were found in the protein pattern. The content of total cholesterol and phospholipid in vesicles shed spontaneously or after detergent treatment was nearly identical, however, significant differences were found in the fatty acid composition of the main phospholipids. The content of polyunsaturated fatty acids (linoleic and arachidonic acid) increased in the order: spontaneously shedded membranes, detergent induced vesicles, conventional purified plasma membranes. These results are discussed in terms of the heterogeneous composition of areas of the thymocyte plasma membrane. PMID- 6243482 TI - Mechanism of action of Clostridium perfringens enterotoxin. Effects on membrane permeability and amino acid transport in primary cultures of adult rat hepatocytes. AB - Purified enterotoxin from the bacterium Clostridium perfringens rapidly decreased the hormonally induced uptake of alpha-aminoisobutyric acid in primary cultures of adult rat hepatocytes. At 5 min after toxin addition the decrease in alpha aminoisobutyric acid uptake appeared not due to increased passive permeation (estimated with L-glucose) or to increased alpha-aminoisobutyric acid efflux. When short uptake assay times were employed a depression of alpha-aminoisobutyric acid influx was observed in toxin-treated hepatocytes. The depression of alpha aminoisobutyric acid influx was correlated with a rapid increase in intracellular Na+ (estimated using 22Na+) apparently effected by membrane damage. In contrast, the uptake of cycloleucine in the presence of unlabeled alpha-aminoisobutyric acid (assay for Na+-independent amino acid uptake) by hepatocytes treated with toxin for 5 min was decreased to only a small extent or not at all depending upon experimental design. At later times, C. perfringens enterotoxin increased the exodus of L-glucose, 3-O-methylglucose and alpha-aminoisobutyric acid from pre loaded cells indicating that the toxin effects progressive membrane damage. When enterotoxin was removed by repeated washing after 5--20 min the decay of alpha aminoisobutyric acid uptake ceased and appeared to undergo recovery towards the hormonally induced control level. The degree of recovery of alpha-aminoisobutyric acid uptake was inverse to the length of time of exposure to toxin. Adding at 10 min specific rabbit antiserum against C. perfringens enterotoxin without medium change also reversed the effect of toxin on increased intracellular 22Na+, and on the exodus (from preloaded cells) of alpha-aminoisobutyric acid, L-glucose, and 3 O-methylglucose. PMID- 6243483 TI - Boundary lipids and protein mobility in rhodopsin-phosphatidylcholine vesicles. Effect of lipid phase transitions. AB - Purified rhodopsin from bovine retina has been incorporated into phospholipid bilayers. Dimiristoylphosphatidylcholine, dipalmitoylphosphatidylcholine, dioleylphosphatidylcholine and egg phosphatidylcholine were used as host lipids, with ratio of lipid to protein of 120 : 1 (mol to mol). In order to probe the lipid-protein interface specifically, a spin-labeled fatty acid was covalently bound to rhodopsin via an isocyanate reacting group. A spin-labeled phospholipid was used to probe the bulk lipidic phase while a tightly bound maleimide spin label was used to obtain the protein rotational correlation time by the saturation transfer technique. The following results were obtained: (1) The kinetics of reduction by ascorbate of the spin-labeled fatty acid covalently bound to rhodopsin demonstrate that the alkyl chain attached to the protein is positioned in the membrane in the same way as the alkyl chains of a phospholipid. (2) The EPR spectra of the latter shows two components: a strongly immobilized component and a weakly immobilized component. The ratio of the two depends upon the temperature and on the nature of the phospholipids. (3) The signal of the weakly immobilized component is compared to that obtained in the corresponding pure lipids. The latter signal, assumed to represent non-bounded lipids, indicates a sharp transition at the phospholipid phase transition with dimytristoylphosphatidylcholine or dipalmitoylphosphatidylcholine. The former signal (corresponding to the lipid-protein interface) indicates only a broad transition extending over 7 degrees C with dipalmitoylphosphatidylcholine and almost no transition with dimyristoylphosphatidylcholine. (4) In a similar way, the rotational correlation time of the protein only changes progressively when the phase transition occurs. Our interpretation of the data can be summarized as follows: The immobilized component seen by the EPR technique in the hydrophobic environment of this intrinsic protein very probably reflects protein-protein contacts and thus corresponds to hindrance of the labeled chains, when they are trapped between neighbouring proteins. Below the phase transition lipid segregation whould increase the probability of protein contact. However, over a certain range of temperature, the contact with the protein interface probably at the same time prevents the non-segregated phospholipids from feezing. The differences in the results obtained with the various phosphatidylcholines above their transition temperature suggest that the solubility of rhodopsin in bilayers depends not only on the fluidity of the lipids, but also, to some extent, on the phospholipid chain length. PMID- 6243484 TI - Lipid domain formation and ligand-induced lymphocyte membrane changes. AB - Spectral parameters of spin-labelled phosphatidylcholine, ceramide and cerebroside in the plasma membranes of human blood lymphocytes were measured before and after treatment with various ligands, which included concanavalin-A and phytohemagglutinin. It was found that ligand treatment led to a significant decrease in order of the hydrocarbon chains of the phospholipids. This was accompanied by a clustering of the labelled spingolipids, as estimated by spin spin interaction, and an increase in the order of their hydrocarbon chains. In the untreated cells the cerebroside fatty acid chain was more ordered than that of the phosphatidylcholine. It was considered that the decrease in phospholipid order was brought about by the sequestration of the more rigid sphingolipids into the patches and caps formed by receptor-ligand complexes. The significance of these changes in lipid distribution and ordering is discussed in relation to the activation of membrane enzyme systems by mitogenic ligands. PMID- 6243485 TI - Inhibition of synthesis of ribosomal proteins and of ribosome assembly after infection of L cells with vesicular stomatitis virus. AB - The effect of infection of mouse L cells by vesicular stomatitis virus on the synthesis of ribosomal proteins was investigated using two-dimensional polyacrylamide gel electrophoresis to analyze the ribosomal proteins. It was found that the synthesis of nearly all of the cytoplasmic ribosomal proteins examined was inhibited by infection and mostly to the same extent. Analysis of the ribosomal proteins extracted from intact ribosomes indicated that infection also reduces the incorporation of all the ribosomal proteins tested into assembled ribosomes. The inhibition of ribosome assembly was greater than the inhibition of synthesis of ribosomal proteins, suggesting that some other factor was also limiting the assembly of ribosomes. As shown in this report, infection also inhibits ribosomal RNA production. Thus, the decreased assembly of ribosomes in infected cells probably results from the inhibition of synthesis of both ribosomal proteins and ribosomal RNA. PMID- 6243486 TI - Large-scale purification of two forms of active lac operator from plasmids. AB - A practical procedure is described for obtaining milligram quantities of a small (29 nucleotide) Eco RI restriction fragment of DNA containing the Escherichia coli lac operator. A yield of 10--15 mg of operator is obtained from 1 kg of wet cell paste. The resultant operator is shown to be homogeneous and competitively active in filter assays. Two separable but interconvertible forms of lac operator exist in solution, probably linear duplex and hairpin isomers. Only the presumed linear form is active in binding lac repressor by competition assay, but the two isomers are interconvertible by heating to 80 degrees C. The methods described here should be generally applicable for purifying other restriction fragments from plasmids. PMID- 6243487 TI - Mitochondrial biogenesis during fungal spore germination. Purification, properties and biosynthesis of cytochrome c oxidase from Botryodiplodia theobromae. AB - 1. Cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1) was purified from the mycelial fungus Botryodiplodia theobromae by sodium cholate and ammonium sulfate solubilization, ammonium sulfate fractionation, and DEAE cellulose chromatography. The purified enzyme contained 6--7 nmol heme a/mg of protein. The specific activity of the purified enzyme was 2.1--2.3 . 10(3) k (min 1) per mg of protein with 15 mumol ferrocytochrome c and at pH 5.9 and optimal phosphate and Tween 80 concentrations (65 mM and 0.1%, respectively). The Km for ferrocytochrome c was determined to be 1.2--1.3 . 10(-5) M, while at infinite substrate concentration the enzyme catalyzed the oxidation of about 60 mumole of ferrocytochrome c/min per mg of protein. Sedimentation behavior and kinetic evidence suggest that the purified enzyme exists as aggregates of the single molecule. The purified B. theobromae cytochrome c oxidase with its 428 nm Soret absorption maximum may be similar if not identical to oxygenated forms of the enzyme from other fungal species. 2. The purified enzyme was shown by sodium dodecyl sulfate polyacrylamide gel electrophoresis to consist of seven polypeptides with the following respective molecular weights: I, 41 000; II, 28 000; III, 19 000; IV, 14 800; V, 12 800; VI, 11 500; and VII, 9300. Biosynthesis studies showed that the three highest molecular weight polypeptides of the enzyme were synthesized on mitochondrial ribosomes, and the four smaller polypeptides were products of cytoplasmic ribosomes. PMID- 6243488 TI - Phospholipid composition and ultrastructure of A549 cells and other cultured pulmonary epithelial cells of presumed type II cell origin. AB - In order to assess the usefulness of A549, L-2, and AK-D cell lines as model systems for alveolar type II cells, we compared their phospholipid composition to that of fibroblasts grown under similar conditions. The percentage of disaturated phosphatidylcholine and phosphatidylglycerol, key phospholipids of purified surface-active material, was the same in epithelial cells and fibroblasts. When A549 cells were maintained in serum-free media for two days, ultrastructural examination showed an increase in cytoplasmic lamellar inclusions but there was no change in the percentage of disaturated phosphatidylcholine or phosphatidylglycerol. Because the lipid content of these cultured cells was very different from that of freshly isolated rat type II cells, we conclude that their suitability as model cell systems for type II cells is questionable. PMID- 6243489 TI - Spin-labelling of phosphorylase b using a paramagnetic 1-fluoro-2,4 dinitrobenzene derivative. AB - Phosphorylase b (1,4-alpha-D-glucan:1,6-alpha-D-glucan 6-alpha glucosyltransferase, EC 2.4.1.1) can be specifically spin-labelled at a site essential for the catalytic action of the enzyme. A paramagnetic analogue of 1 fluoro-2,4-dinitrobenzene was synthesized and used as a dinitrophenylating agent. Reaction of phosphorylase b with the paramagnetic probe combined with the thiolysis method, leads to spin-labelling of a single -NH2 group (0.75 groups per subunit) with concomitant loss of 50% of the catalytic activity. Dinitrophenylation does not change the sedimentation profile of the enzyme. The ESR spectrum of modified phosphorylase b indicates that the attached label has rather limited segmental mobility and its environment is slightly hydrophobic. Small but subtle conformational changes induced by ligands in this critical site of the macromolecule can be directly detected by the spin-label. Also, sulfhydryl group modification of the spin-labelled enzyme with 5,5'-dithiobis(2-nitrobenzoic acid) has a pronounced effect on the resonance spectrum. PMID- 6243490 TI - Micrococcus radiodurans surface exonuclease. Dimer to monomer conversion by ionizing radiation-generated aqueous free radicals. AB - Micrococcus radiodurans possesses an exonuclease firmly bound to a middle cell wall membrane layer. Aqueous OH. radicals generated chemically or by ionizing radiation cause the immediate release of this enzyme into the surrounding medium. The enzyme is located in a hydrophobic site and can also be released by aqueous n butanol. When extracted by this solvent it is a non-covalently linker dimer and has a molecular weight of 260 000 as determined by gel filtration. When released by radiation generated OH. radicals, the enzyme initially appears in solution as the dimer but is rapidly split by further aqueous radical attack into two 130 000 molecular weight subunits. Hydroxyl radicals are most effective but reducing radicals are also able to monomerize the enzyme. Only the released dimer enzyme is subject to free radical monomerization. Bound dimer enzyme is not split prior to release. No detectable loss of activity or change in catalytic properties accompanies the free radical cleavage of the enzyme. Both subunits of the dimer enzyme possess a tightly bound metal ion (probably Ca2+) required for activity. The monomer but not the dimer enzyme will bind to an anion exchanger. The monomer is susceptible to loss of its metal ion, and consequent inactivation, when exposed to the exchanger in the absence of Ca2+. Besides providing information on some of the immediate non-lethal effects of ionizing radiation, the behavior of this enzyme system demonstrates a potential cellular mechanism by which internally or externally generated free radicals could be utilized by the cell to control various enzymic reactions. PMID- 6243491 TI - 1H-NMR and rosonance Raman spectra of octaethylporphyrinatoiron(III) perchlorate and its mono imidazole adduct. AB - The 1H-NMR spectra and the resonance Raman spectra of intermediate spin complex, octaethylporphyrinatoiron (III) perchlorate (OEP-Fe(III)ClO4) and its mono imidazole adduct have been recorded and analyzed. The perchlorate complex was determined to be an intermediate-spin state (S = 3/2) in dichloromethane. The mono imidazole and 2-methylimidazole adducts of OEP-Fe(III)ClO4 were of the high spin state in dichloromethane, which is a good model for the ferrihemoproteins such as metmyoglobins. The spin state of OEP-Fe(III)ClO4 varies the polarity of solvent from typical high-spin (S = 5/2) to typical low-spin (S = 1/2) state including intermediate-spin state (S = 3/2). The resonance Raman studies of the intermediate-spin complex in various solvents indicate that the complex is a plausible model to reproduce anomalous physico-chemical properties of the ferricytochrome c' at physiological condition. PMID- 6243492 TI - Electron spin relaxation of the electron paramagnetic resonance spectra of cytochrome c. AB - The progressive power saturation of the electron paramagnetic resonance (EPR) spectrum of ferricytochrome c has been investigated in order to determine the spin-lattice relaxation time of the center. We have generalized the usual saturation treatments to include the effects of extended sample size and anisotropic g values as well as derivative spectra. We find that the results are consistent with a T7 power law in the temperature range 6--25 K. At temperatures above 25 K the relaxation time is too short for successful power saturation. Observation of the linewidth shows that the relaxation behavior continues as a first-order Raman process to 50 K. PMID- 6243494 TI - A comparison between adenylate cyclase solubilized from normal and Rous sarcoma virus-transformed chicken embryo fibroblasts. AB - The specific activity of adenylate cyclase in membrane preparations obtained from Rous Sarcoma virus-transformed chicken embryo fibroblasts is two to four times lower than that found in untransformed membranes. Adenylate cyclase was solubilized from normal and transformed membranes in order to evaluate the influence of the membrane phase on the properties of the enzyme. Adenylate cyclase in normal and transformed membranes differed in specific activity, V for ATP, activation entropies, sensitivity to Ca2+, and stability at 37 degrees C. Solubilization with Brij 96 abolished or greatly reduced these differences. These data suggest that the differences between adenylate cyclase activities in normal and transformed chicken embryo fibroblasts are due either to differential modulation of enzyme activity by an effector which requires intact membranes for its effects, or indirect effects due to altered membrane properties. PMID- 6243493 TI - The isolation and purification of cytochrome c1 from bovine heart. AB - A large-scale isolation method for cytochrome c1 from beef heart is presented, based in principle on the procedure of Yu et al. (Yu, C.A., Yu, L. and King, T.E. (1972) J. Biol. Chem. 247, 1012--1019). Optimal solubilization of cytochrome c1 from succinate-cytochrome c oxidoreductase was achieved with 15% beta mercaptoethanol, 1.5% cholate, 0.5% deoxycholate in 8% saturated ammoniun sulphate. The protein is purfied to a higher degree by chromatography on DEAE cellulose and Ultrogel AcA 44. The method is reproducible and gives highly purified cytochrome c1 with a yield from succinate-cytochrome c oxidoreductase of 40%. The purified cytochrome c1 contains 32 nmol of heme/mg protein and has a spectral heme-to-protein ratio (Ared417nm/Ax276nm) of 2.7. Reduced cytochrome c1 is oxidized very rapidly by ferricytochrome c (k = 3 . 10(7) M-1 . S-1 at 10 degrees C, 100 mM potassium phosphate (pH 7.0) and 1% Tween 20). Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate shows that the isolated protein consists of one peptide, with a molecular weight of 31 000, carrying the chromophore. In the presence of 1% sodium cholate or 1% Tween 80, cytochrome c1 is in the monomeric state, whereas at lower concentrations of detergent the protein aggregates. The aggregation of cytochrome c1 is found to be reversible. PMID- 6243495 TI - Oxidation by superoxide of tocopherols dispersed in aqueous media with deoxycholate. AB - alpha-Tocopherol dispersed in aqueous media with deoxycholate was found to be oxidized, at a physiological pH, by a xanthine-xanthine oxidase system. This reaction was completely inhibited by the addition of superoxide dismutase, whereas catalase and mannitol (scavenger of hydroxyl radical) did not affect the reaction. This finding indicates that the oxidation of alpha-tocopherol is caused by O2. The reaction product formed was identified as 8 alpha-hydroxy-alpha tocopherone by thin-layer chromatography and ultraviolet spectroscopy. The product was found to change spontaneously to alpha-tocopherol quinone. beta-, gamma-, and delta-tocopherol dispersed with deoxycholate also reacted with O2. The reaction of tocopherols dispersed in the micellar form may be considered as a model of in vivo reaction of tocopherols, since tocopherols are present in tissues largely in the membranes, where O2 is known to be generated. PMID- 6243496 TI - Studies on the nature of interaction between follicle-stimulating hormone and the testicular receptors. AB - Two previous reports from this laboratory showed that the binding of 125I-labeled human choriogonadotropin and 125I-labeled human luteinizing hormone to rat testicular receptors is partially irreversible and the binding parameters obtained from Scatchard analysis of the data can be drastically altered simply by changing the reaction volume of the binding assays (Chen, C.J.H., Lindeman, J.G., Trowbridge, C.G. and Bhalla, V.K. (1979) Biochim, Biophys. Acta 584, 407--435; Bhalla, V.K., Trowbridge, C.G., Chen, C.J.H., Lindeman, J.G. and Rojas, F.J. (1979) Biochim, Biophys. Acta 584, 436--453). It is reported herein that the binding reaction between follicle-stimulating hormone and testicular receptors displays very similar characteristics. The results support the previous conclusion that receptor concentrations fluctuate in the membranes and that the extent of their loss from tissue membranes in vitro is dependent upon time and temperature of incubation, the volume of buffer present, and the quantity of hormone used. PMID- 6243497 TI - Bone remodelling induced by physical stress is prostaglandin E2 mediated. PMID- 6243498 TI - Biochemical studies of taste sensation. IX. Enhancement of L-[3H]glutamate binding to bovine taste papillae by 5'-ribonucleotides. AB - The interaction of the taste substance monosodium L-glutamate with taste receptors has been investigated. Binding of L-[3H]glutamate was measured to preparations of bovine circumvallate (taste) papillae (type I preparation) and to control tongue epithelial preparations (type II preparation) devoid of taste receptors. Binding is operationally defined using a membrane filtration assay. Substantially greater binding occurred to the type I preparation than to the type II preparation, and the binding to the type I preparation showed evidence of saturation. The apparent Kd of L-glutamate was estimated to be in the range of 20 -30 mM. The unique taste effect of L-glutamate was considered to depend importantly on its demonstrated synergism in combination with certain 5' ribonucleotides. A several-fold enhancement of binding of L-[3H]glutamate occurred in the presence of certain 5'-ribonucleotides. 5'-GMP, 5'-IMP and 5'-UMP each increased the binding of L-[3H]glutamate, while 5'-XMP, 5'-AMP and 5'-CMP did not. None of these nucleotides affected the lower level of binding to the type II preparation. Neither the free bases, adenine and guanine, their nucleosides nor their di- or triphosphonucleotides were effective in increasing L [3H]glutamate binding to the type I preparation. The nucleotide specificity of the glutamate binding enhancement therefore shows a marked similarity with the nucleotide specificity in evoking the synergistic taste effect in humans. PMID- 6243499 TI - Lumped and population stochastic models of skeletal muscle: implications and predictions. AB - Lumped models of skeletal muscle have been assumed a) in the design of experiments and the interpretation of experimental findings, b) in theoretical studies. In this paper, a population model that takes into account the differing properties and separate (independent) activation of motor units is presented as the most appropriate for muscle. A realistic (for muscle) transformation, population leads to lumped model, resulting in the lumping of motor unit neural signals or system responses, is proposed. On this basis, the possibility of modelling muscle as a single system is examined; and the consequences of treating muscle as a lumped system, in experiments or theoretical studies, are discussed. Also, the advantages of lumping, in models of muscle, are reviewed. Predictions of a computer population model, together with actual recordings from a hand muscle, are used to confirm the results of the analysis. PMID- 6243500 TI - Enzyme formation during solid-substrate fermentation in rotating vessels. AB - Aspergillus awamori NRRL 4869 was cultured on the solid substrate, wheat bran, in a modified Rollacell apparatus to produce alpha-galactosidase and invertase. The swivel cap on the elongated bottle permits the introduction of air while the bottle rotates. Parameters of air flow rate (0.05-0.2 liter/kg/min), rpm (0.15-15 rpm), and weight of solids (150 and 300 g) were varied. At low air flow rates (0.05 liter/kg solids/min), alpha-galactosidase production was minimal independent of the rotation rate. At 0.15 rpm and 0.2 liter/kg solids/min air flow rate, invertase production ceased after five days; whereas alpha galactosidase production continued. The modified Rollacell can be a useful apparatus for studying solid-substrate cultures. PMID- 6243501 TI - The myeloid progenitor cell--its value in predicting hematopoietic recovery after autologous bone marrow transplantation. PMID- 6243502 TI - A potential role for hypochlorous acid in granulocyte-mediated tumor cell cytotoxicity. PMID- 6243503 TI - Pain sensitivity and opioid activity in genetically and experimentally hypertensive rats. AB - Pain sensitivity was studied in renal and DOCA-salt hypertensive rats, and in two strains of rats derived from the same parental strain for their sensitivity (H) or immunity (N) to hypertension induced by DOCA-salt treatment. Experimentally hypertensive rats, and H and N rats were less sensitive to painful stimuli than their appropriate controls, as assessed in the hot-plate and paw pinch tests. Naloxone reversed this hypoalgesia in both experimentally and genetically hypertensive rats while it did not affect blood pressure in any rat-type tested. Opioid activity was measured with the radioreceptor assay in several brain regions and pituitary gland of both experimentally and genetically hypertensive rats. Experimentally hypertensive rats had a 45% higher level of opioid activity in the spinal cord compared to control. Rats of the H and N strains both exhibited higher levels of opioid activity in the spinal cord, hypothalamus and pituitary. It is suggested that control systems for blood pressure and pain sensitivity are closely associated in the rat. PMID- 6243504 TI - GABA receptors in bovine cerebral blood vessels: binding studies with [3H]muscimol. AB - [3H]Muscimol, a potent GABA agonist used to label GABA receptor sites in brain and invertebrate striated muscle, was found to bind specifically to sites in a crude membrane fraction prepared from bovine cerebral blood vessels. Specific [3H]muscimol binding was saturable of high affinity (Kd = 41 nM), and was selectively inhibited by GABA, specific GABA agonists, and the antagonist bicuculline with potencies similar to what has been found for GABA receptors in mammalian brain. GABA and several GABA agonists including muscimol have been reported to dilate isolated cerebral arteries, but not peripheral blood vessels. The pharmacology of the [3H]muscimol binding site correlated well with that of the vasodilatory response. No significant specific [3H]muscimol binding was detected in aorta and mesenteric arteries. The characteristics of the cerebrovascular muscimol binding site thus are indicative of a physiologically relevant GABA receptor associated with cerebral blood vessels. These findings suggest a direct role for GABA in cerebral vascular function. PMID- 6243505 TI - Muscle spindle function in organophosphorus neuropathy. AB - The contribution of muscle spindle dysfunction to the neurological signs o delayed organophosphorus neuropathy was investigated in the hindlimbs of cats intra-arterially injected with 2 mg/kg of diisopropylfluorophosphate (DFP). In this model of a delayed peripheral neuropathy, the animals exhibit a peculiar high-step gait and a sluggish response to noxious stimuli. These signs initially appear 14 days and are maximum 21--28 days after DFP administration. The position sensitivities of secondary but not primary soleus muscle spindles were depressed at 14 days after DFP. At 21 days after DFP, both primary and secondary endings had attenuated position sensitivities and significantly elevated thresholds. Spindle function was normal at 56 days after DFP exposure. The onset, peak and recovery of soleus muscle spindle dysfunction corresponded to those in alpha motor axons, indicating the mixed sensory motor nature of organophosphorus neuropathy. Thus, impairment of both sensory and motor functions contributes to the neurological signs of this neuropathy. PMID- 6243506 TI - Small cell carcinoma of the lung: experience with six-drug regimen. PMID- 6243507 TI - Methotrexate with citrovorum factor rescue: reduced chemotherapy toxicity in the management of gestational trophoblastic neoplasms. AB - The comparative systemic toxicity of methotrexate (MTX) with citrovorum factor rescue (CF), MTX alone and actinomycin-D (Act-D) in the treatment of gestational trophoblastic neoplasms (GTN) was evaluated in the present study. Treatment with MTX-CF was associated with only a 4% incidence (1 of 25 patients) of hepatic and/or hematologic toxicity and total absence of either a generalized rash or marked alopecia. In contrast, both MTX alone and Act-D were associated with a 48% incidence (12 of 25 patients) of hepatic and/or hematologic toxicity. Actinomycin D also induced a generalized rash and marked alopecia in 24% (6 of 25 patients) and 52% (13 of 25 patients) of the patients respectively. We found that MTX-CF is the least toxic single agent chemotherapeutic regimen in the management of GTN. PMID- 6243509 TI - Chordoid sarcoma: ultrastructural evidence supporting a synovial origin. AB - A case of chordoid sarcoma which presented as a painful mass on the dorsum of the right hand in a 72-year-old man was studied by light and electron microscopy. The tumor was composed of lobules separated by thin connective-tissue bands. At the periphery of the lobules, the cells were epithelioid in appearacne and there were numerous nests of clear cells. From the periphery, stellate and spindle shaped cells were radially oriented and formed a loose cobweb arrangement in an abundant loose ground substance. Distinctive ultrastructural features included pseudoacinar formation, microvilli, long cytoplasmic filopodia (often with complex interdigitations), numerous desmosomes, partial basal lamina, scanty endoplasmic reticula, and numerous intracytoplasmic filaments 80--100 A in width. We believe these ultrastructural features indicate a synovial origin of this uncommon neoplasm. PMID- 6243508 TI - Immunohistochemical localization of glial fibrillary acidic protein in human glial neoplasms. AB - The presence and distribution of glial fibrillary acidic protein in fixed, paraffin embedded tissue were studied in 85 human intracranial neoplasms, using the peroxidase-anti-peroxidase method. In some cases, indirect immunofluorescence of frozen sections was used as well. In normal tissue, only the cell processes and perikarya of fibrous astrocytes were stained. Immunostaining was also observed in the following glial neoplasms: astrocytomas (all varieties), astroblastoma, subependymal giant cell astrocytoma, subependymoma, glioblastoma multiforme and ependymoma. The astrocytic elements of mixed gliomas and of medulloblastomas undergoing glial differentiation were likewise strongly stained. In contrast, oligodendrogliomas, meningiomas, pituitary adenomas, sarcomas, lymphomas and metastatic carcinomas were negative. Either a perikaryal or a diffuse fibrillary staining pattern was observed. Combination of the two patterns occasionally occurred. The perikaryal staining was prominent in gemistocytic astrocytomas and in astroblastomas. A distinct negative correlation existed between the degree of anaplasia and the intensity of immunostaining. PMID- 6243510 TI - Focal acinar cell dysplasia in human pancreas. AB - A series of 108 prospectively collected human pancreata were evaluated histologically for the presence of acinar cell and ductal lesions. Foci of dysplastic acinar cells were present in 44% of the series. Some of the focal acinar cell abnormalities were similar to atypical acinar cell nodules which have been described in carcinogen-treated experimental animals. The incidence of nodules was higher among patients with a history of heavy cigarette smoking than among nonsmokers, and among patients with a history of alcohol abuse than among abstainers. The presence of dysplastic acinar cell nodules in a pancreas seemed unrelated to the presence of cancer in other sites, or diabetes. Ductal epithelial abnormalities were more frequent than focal acinar cell dysplasia. PMID- 6243511 TI - Hypertrophic pulmonary osteoarthropathy and metastases from a malignant fibrous histiocytoma. AB - Malignant fibrous histiocytoma is a recently accepted member of the mesenchymal group of tumors. Hypertrophic pulmonary osteoarthropathy is rarely seen with metastatic lung disease but when it occurs it is most frequently described with sarcomatous tumor metastases. In the case reported here, this phenomenon developed with pulmonary metastases from a malignant fibrous histiocytoma, indicating that this tumor resembles other sarcomas in giving rise to this unusual clinical syndrome. PMID- 6243512 TI - Ossifying tumor of infantile kidney: report of two cases. AB - Two patients, both male infants, presented with hematuria and were found to have small calcified intrarenal masses interpreted as calculi radiographically. These were found at surgery to be firmly adherent to parenchyma. Dense, stone-like cores, after decalcification, were found to be composed of bone, while the periphery was composed of uniform, undifferentiated cells. We believe these tumors were derived from urothelium rather than the metanephros, and that they represent yet another benign variant of pediatric renal tumors. PMID- 6243513 TI - Biosynthesis in vitro of mono- and di-sialosylgangliosides from gangliotetraosylceramide by cultured cell lines and young rat brain. Structure of the products, and activity and specificity of sialosyltransferase. AB - Incubations in vitro of GA1, labeled with 3H in the terminal D-galactopyranosyl group, with nonradioactive CMP-NeuNAc in the presence of homogenates of C21 rat brain glial cells, NIE mouse neuroblastoma cells, 3T3 mouse fibroblasts, SV 40 transformed 3T3 cells, chick embryo fibroblasts, Rous sarcoma virus-transformed chick embryo fibroblasts, and 9-day old rat brain resulted in all cases in the formation in high yield of GM1b, in which the neuraminidase-labile NeuNAc group is linked at O-3 of the terminal D-galactosyl residue, as shown by permethylation studies. No trace of the naturally occurring neuraminidase-stable GM1a was detected in any case. In addition, with NIE cells, and normal and RSV-transformed chick embryo fibroblasts, a disialosylganglioside (GD1) differing from GD1a and GD1b, and bearing only one substituent at O-3 of the terminal D-galactopyranosyl residue was formed. It was also biosynthesized from GM1b and CMP-NeuNAc by NIE and chick embryo cells but not by C21 cells, or rat brain. However, C21 cells and rat brain were capable of synthesizing GD1a from GM1a. Periodate oxidation degraded both NeuNAc groups in GD1 to a 7-carbon fragm:nt, indicating lack of substitution at O-8. GM1b could not be detected as a natural product in rat brain. PMID- 6243514 TI - Production of neutralizing antibody to rabies and vesicular stomatitis viruses by hybrid cell lines. PMID- 6243515 TI - In vitro killing of tumor cells by soluble products of activated guinea pig peritoneal macrophages. PMID- 6243516 TI - Molecular requirements for trinitrophenyl recognition by antihapten cytotoxic T lymphocytes. PMID- 6243517 TI - A requirement for three cell types for in vitro generation of specific secondary cell-mediated cytotoxic response against SV40-induced tumor-associated antigens in mice. PMID- 6243518 TI - Atenolol: once-daily cardioselective beta blockade for angina pectoris. AB - The physiology, pharmacokinetics and efficacy of atenolol, a cardioselective beta adrenergic blocking agent, were evaluated in 10 patients with stable angina pectoris in a single-blind, dose-ranging study. After a 1-month control placebo period, atenolol was administered once daily at dosages of 25, 50, 100 and 200 mg for 2-week periods. All patients had fewer anginal attacks and consumed fewer nitroglycerin tablets than mg for 2-week periods. All patients had fewer anginal attacks and consumed fewer nitroglycerin tablets than during the placebo period. Twenty-four-hour ambulatory ECG recordings showed a decrease in mean hourly heart rate throughout the dosing period, with preservation of diurnal variation. Maximal, symptom-limited, treadmill exercise tests performed 3 hours after drug ingestion showed significantly increased exercise time and decreased double products for all doses, but especially with 100-mg and 200-mg doses. Exercise time 24 hours after drug ingestion continued to show a decrease in maximum heart rate and double product, with 100-mg and 200-mg doses again being most effective. Atenolol serum levels correlated with percent reduction in exercise heart rate and increased exercise time. Serum levels rose linearly, with an average elimination half-life of about 10 hours after chronic oral dosing. Thus, atenolol was an effective antianginal agent and suppressed resting and exercise-stressed heart rate for 24 hours after ingestion when given in a 100-mg or 200-mg dose once daily. PMID- 6243520 TI - Estimation of the specific activity of radiolabeled corticotropin and insulin by precipitation. PMID- 6243519 TI - False-negative results for urinary phenothiazines and imipramine in Forrest's qualitative assays. AB - When a series of patients' urine samples supplemented in vitro with chlorpromazine or imipramine was assayed with the Forrest qualitative assays, we observed an occasional false-negative result, which we found was attributable to interference by ascorbic acid. It interferes with the reagent, not with the analytes, in both assays. We easily eliminated this interference with the phenothiazine test by using an anion-exchange resin. Eliminating the interference with the assay for imipramine, however, is more difficult; false-negative results can be obtained even after ion-exchange chromatography if the imipramine concentration is less than 50 mg/L. PMID- 6243521 TI - Association of a lymphocyte purine enzyme deficiency (5'-nucleotidase) with combined immunodeficiency. PMID- 6243522 TI - A retrospective analysis of renal abnormalities detected on bone scans. PMID- 6243523 TI - Uptake of Tc-99m-PIPIDA in pulmonary metastases from a hepatoma. AB - Metastatic pulmonary nodules from a well-differentiated hepatoma were well demonstrated by a Tc-99m-labeled hepatobiliary imaging agent. Uptake of this type of radionuclide by metastases from a primary hepatic malignancy has not previously been reported. Such radiopharmaceuticals may prove useful in the future as imaging agents for primary hepatobiliary tumors. PMID- 6243524 TI - Sensitivity and specificity of Tc-99m-pyrophosphate myocardial scintigraphy for the detection of acute myocardial infarction. AB - Tc-99m-pyrophosphate myocardial scintigraphy was performed on 1,077 patients admitted to the Coronary Care Unit. Results of scintigraphy were compared to the diagnosis as established by ECG, enzymes, and clinical findings to determine the sensitivity and specificity of scintigraphy for the diagnosis of acute myocardial infarction (AMI). Scintigrams were graded according to the intensity of myocardial radioactivity and the distribution pattern of activity as either diffuse or localized. In a coronary care unit, a scintigram of positive intensity grade is 92% sensitive and 68% specific for the diagnosis for AMI. A localized pattern of myocardial radioactivity is 66% sensitive and 93% specific for AMI. With a localized pattern of the highest intensity, the sensitivity is 28% with a specificity of 99.8% for AMI. Therefore, a myocardial scintigram of normal intensity grade excludes the diagnosis of AMI with a 92% probability. A localized pattern is a strong indicator of an AMI and a localized pattern of the greatest intensity is very specific for AMI. PMID- 6243525 TI - Peripheral resistance to the cellular action of insulin in obese diabetic subjects in vivo. AB - 1. The concentrations of adenosine 3': 5'-cyclic monophosphate (cyclic AMP) in human adipose tissue were studied after intravenous insulin administration (0.3 unit/kg body weight) in obese diabetic and obese non-diabetic subjects. 2. The declines in plasma glucose, glycerol and free fatty acids in the two groups after insulin were similar if allowances were made for the fasting hyperglycaemia in the diabetic subjects. 3. Insulin in vivo lowered the concentrations of cyclic AMP in adipose tissue from non-diabetic subjects. 4. Insulin administration in vivo did not alter the tissue concentrations of cyclic AMP in adipose tissue of obese diabetic subjects. This lack of effect of insulin provides evidence for tissue resistance in vivo to the action of insulin in diabetes mellitus. PMID- 6243526 TI - Preventive mental health--now! PMID- 6243527 TI - Decreased renal function in association with administration of 1,25 dihydroxyvitamin D3 to patients with stable, advanced renal failure. AB - A controlled study of the effects of 1,25-dihydroxycholecalciferol (1,25[OH]2D3) and vitamin D3 (D3) was performed in 18 non-dialyzed patients with chronic renal failure (CRF) (creatinine clearance below 35 ml/min) and mild renal osteodystrophy. After 6 months observation of the spontaneous course, the patients were randomly allocated to 6 months oral treatment with either 1,25(OH)2D3 or D3 in initial daily doses of 1 and 100 microgram, respectively, combined with 0.5 g calcium (Calcium Sandoz). 1,25(OH)2D3 had a fast normalizing effect on the biochemical changes of calcium metabolism. D3 had similar, but less pronounced effects. The percent fall in creatinine clearance was greater during than before treatment in all patients on 1,25(OH)2D3 (p less than 0.01) and in 7 of 9 patients on D3 treatment (n.s.). Deterioration of renal function is a major limitation to clinical use of 1,25(OH)2D3 (and D3) in non-dialyzed patients with CRF. In fact, the decreased formation of 1,25(OH)2D3 seen in CRF might protect renal function through the abnormalities in mineral metabolism. PMID- 6243528 TI - Controlled trial of the effects of 1,25-dihydroxycholecalciferol in patients treated with regular dialysis. AB - In a double-blind controlled study, 15 patients received 1,25 dihydroxycholecalciferol (1,25[OH]2D3) (0.5-1.5 microgram/day) and 16 patients received vitamin D3 (D3) (400-1,200 IU/day). The patients receiving 1,25(OH)2D3 had a rise in mean serum calcium concentration from 9.05 +/- 0.15 to 10.25 +/- 0.20 mg/dl (p less than .001) with a return to 9.37 +/- 0.16 (p less than .001) in the post-control period; however, hypercalcemia (greater than 11.5 mg/dl) occurred in 5 of 15 patients. Likewise, patients who received 1,25(OH)2D3 but not those given D3 had a reversible decrease in immunoreactive parathyroid levels. 9 of 12 patients given D3 had serial iliac crest bipsies showing histologic deterioration, while 6 of 7 patients who received 1,25(OH)2D3 were improved or unchanged (p less than 0.025). Bone mineral and calcium content decreased in patients on D3 (p less than .05) but not in those on 1,25(OH)2D3. We conclude that the administration of 1,25(OH)2D3 to dialysis patients: (1) has a calcemic effect. (2) decreases levels of immunoreactive parathyroid hormone, and (3) is associated with histologic improvement in bone disease. PMID- 6243529 TI - Hepatoma presenting as a single cavitary lung mass. AB - A patient who had had a lobectomy for a large cavitary lung mass died one month later. An autopsy was performed and pathologic review of surgical and postmortem specimens confirmed that the original lung lesion was metastatic hepatoma. Excavating solitary metastases from primary adenocarcinomas represent the rarest form of cavitary metastatic lesion, and this is the first report of hepatocellular carcinoma presenting as a single cavitary lung mass. PMID- 6243530 TI - Inhibitory effects of aminoglycoside antibiotics on reduction of cytochrome c from Candida krusei. AB - Five aminoglycoside antibiotics (AGAs)--kanamycin (KM), bekamycin (AKM), dibekacin (DKB), ribostamycin (RSM) and paromomycin (PRM)--were studied for their effects on the nonenzymic reduction of cytochrome c by FeSO4 (Yamabe's system). Their inhibitory activity was in the order: DKB greater than AKM greater than KM greater than RSM greater than PRM. As this order correlated closely with that of the antibacterial activity of AGAs, Yamabe's system has proved useful in predicting the latter activity. Divalent metal ions other than Fe2+ enhanced the AGA-dependent inhibition of Yamabe's system in the order: Cu2+ greater than Mn2+ greater than Zn2+ greater than Co2+ greater than Ni2+ greater than. This order was similar to that of stability constants with general chelators except for the low positions of Ni2+ and Co2+. These findings suggested a metal chelation with free or bound Fe2+ for the action mechanism of AGAs on Yamabe's system and the bacterial growing system. The antagonistic effects of exogenous Fe2+ on the antibacterial activity against Staphylococcus aureus and Escherichia coli as measured by the agar dilution method supported this concept. A dual relationship of molecular structure with chelating and antibacterial activities demonstrated the importance of high molecular basicity in a potent AGA. However, the combination effect of pipemidic acid (stimulator on Yamabe's system) with KM was different from that with 1,10-phenanthroline (inhibitor on Yamabe's system) as measured by Dye's method using Pseudomonas aeruginosa. PMID- 6243531 TI - Controlled clinical trial comparing intra-incisional cephaloridine and Polybactrin Spray. AB - 300 patients undergoing various operations were randomly allocated to receive, intra-incisionally, just before skin suture, either a solution of 1 g cephaloridine or Polybactrin aerosol. An equal number of patients were allocated to each group, and various factors likely to influence the incidence of wound infections were evenly distributed. 13 wound infections (9.8%) developed in the cephaloridine group and 28 (20.1%) in the Polybactrin group (p less than 0.02). In the former group, the infections were milder and there were 44 fewer patient days of hospitalisation. The difference in infection rates for 'potentially contaminated and contaminated' operations was greater (p less than 0.01), in favour of cephaloridine. Other differences are discussed and some reasons for the superiority of cephaloridine over other agents (e.g., povidone-iodine, ampicillin) are advanced. PMID- 6243532 TI - Effect of metoclopramide on interdigestive myoelectric activity in the conscious dog. AB - The effect of two-hour infusions of metoclopramide at five different doses on interdigestive intestinal electrical activity was studied in four conscious fasting dogs. Spike activity during the infusions was quantitatively compared with activity during preceding and following periods of saline infusion. The effect of the drug was the enhancement of spike activity during migrating myoelectric complexes (MMC) without disruption of the fasting pattern; the effect was most marked in the proximal small intestinal and diminished distally. As in other published studies with metoclopramide, its effects were variable and not dose dependent. The enhancement of the MMC by an exogenous stimulus, not previously reported, provides indirect evidence for cholinergic mediation of cyclical motor activity, and also suggests a rational basis for therapy. PMID- 6243533 TI - Ontogenetic determinants of behavioral responses to morphine in rats. AB - Male Sprague-Dawley rats ranging in age from 20 to 110 days were injected with two doses of morphine sulphate, and examined for behavioral activation and catalepsy. Behavioral activation increased with age, while sensitivity to catalepsy declined. Ontogenetic and pharmacological responses suggest possible separate mediation of activation and catalepsy. PMID- 6243534 TI - Laboratory Verification of "heavy" and "light" users of cannabis. PMID- 6243535 TI - A possible role of catecholamines and (Na+ + K+)ATPase in the ethanol withdrawl syndrome. AB - Chronic ethanol intoxication leads to an increase in the intracellular Na+/K+ ratio. It is suggested that this derangement is counteracted by catecholamines via an activation of (Na+ + K+)ATPase. This hypothesis is discussed in relation to the symptomatology of ethanol withdrawal. PMID- 6243536 TI - Neutralization of the effect of delta 9-tetrahydrocannabinol on barbiturate sleeping time by specific active immunization. AB - Adult mice were actively immunized with delta 9-tetrahydrocannabinol-bovine serum albumin (delta 9-THC-BSA) conjugate. Control animals were immunized with BSA alone. While the administration of pentobarbital and delta 9-THC to control animals resulted in the well known prolongation of the barbiturate sleeping time, in mice immunized with delta 9-THC-BSA conjugate this effect was almost completely neutralized. PMID- 6243537 TI - In vivo and in vitro properties of anti-delta 9-tetrahydrocannabinol antibody. AB - An immune serum to cannabinoids was produced in rabbits. It was tested in vitro by immunoprecipitation, hemagglutination and hemagglutination-inhibition tests. In vivo, when passively transferred into mice, it prevented the effect of delta 9 tetrahydrocannabinol on the barbiturate sleeping time. PMID- 6243538 TI - Examination of interspecies differences in renal and skeletal receptor binding and adenylate cyclase stimulation with human calcitonin. PMID- 6243539 TI - Isolation of viable rat ventral prostate epithelial and nonepithelial cells. AB - A procedure is described for the dispersion, partial purification, and identification of epithelial and nonepithelial cells from the rat ventral prostate, the latter based in part upon the ability of cells to bind androgen. Since initial efforts to mechanically disrupt prostatic tissue at 2 C lysed many cells, minced rat prostates were exposed to collagenase at 37 C and further dispersed by repetitive pipetting and passage through a tissue sieve. Washed cells in culture medium were centrifuged through an isokinetic Ficoll gradient from which three visible fraction (1, 2, and 4) and a less definite fraction 3 were harvested. Characterically, fraction 1 contained cellular debris; fraction 2 contained round nucleated cells, fewer elliptically shaped cells, red blood cells, and rare free cell nuclei; fraction 3 contained somewhat larger elliptical and round cells; and fraction 4 contained larger round and elliptically shaped cells. These were epithelial cells, as judged by electron microscopy. Isolated prostate cells from rats castrated for 24 h were incubated with [3H]testosterone; 80-90% of the retained radioactivity, the majority of which was dihydrotestosterone, was associated with washed cells from fraction 4. Similar results were obtained after in vivo administration of labeled androgen and subsequent analysis of radioactivity in cells from these fractions. Histochemically and enzymatically demonstrable formalin-insensitive acid phosphatase was increased in bands 3 and 4, which were enriched in epithelial cells. Many cells in fractions 2-4 were viable before and after exposure to Ficoll, as estimated by their ability to exclude trypan blue, incorporate radioactive uridine into RNA, generate cell monolayers during 1-4 weeks of culture, and actively metabolize androgens. Compared to fraction 4, cells from fraction 2, considered to be enriched in nonepithelial cells, actively metabolized but bound much less [3H]testosterone and its metabolites. A number of epithelial cells in fraction 4 isolated from prostates dissociated at 2 C were associated with typical-C-type RNA viruses. PMID- 6243540 TI - The interaction of castration and adrenalectomy on pituitary responses to loss of target gland negative feedback in the male rat. PMID- 6243541 TI - Relationships between thyroid hormone and glucocorticoid effects in GH3 pituitary cells. AB - The interrelationships between thyroid hormone and cortisol actions were investigated in GH3 pituitary tumor cells. When GH3 cells were grown in thyroid hormone-deficient medium, cortisol did not affect the concentration of TRH receptors. Both thyroid hormones and TRH normally decrease the number of TRH receptors, and cortisol inhibited down-regulation by both hormones. TRH caused a greater increase in PRL synthesis when TRH receptors were high in the presence of cortisol and T3 than when TRH receptors were low (T3 alone). In the presence of cortisol, higher concentrations of T3 were required to decrease TRH receptors, while lower concentrations were necessary to stimulate GH synthesis. Cortisol and T3 alone stimulated GH synthesis 6- and 10-fold, respectively, while together they caused an 830-fold increase. In contrast, T3 did not alter the inhibition of PRL synthesis by the glucocorticoid. Cortisol did not significantly affect the amount of [125I]T3 bound to nuclei from cells incubated in thyroid hormone deficient or T3-supplemented medium (approximately 100 and approximately 25 fmol/mg cell protein). The data suggest that cortisol modifies thyroid hormone action at a step subsequent to T3 receptor binding. PMID- 6243542 TI - Stimulation of ornithine decarboxylase activity by insulin in developing rat brain. AB - Insulin administered ip or intracisternally (ic) increased the activity of ornithine decarboxylase (ODC) in whole brains and brain parts of neonatal rats. Maximal stimulation of activity occurred 4-5 h after ip administration. At the highest doses, insulin stimulated ODC activity by up to 5- and 8-fold after ip and ic injection, respectively. The same amount of insulin given ic caused greater increases in activity than when given ip. Insulin stimulated ODC activity in 2-day-old and in 17- to 60-day-old rats but not in 5- or 9-day old neonates or 80-day-old adults. When insulin-induced hypoglycemia was prevented by giving dextrose, the stimulation of ODC activity was approximately the same as that in animals receiving insulin without dextrose. This indicates that insulin-induced stimulation of brain ODC activity was not caused by insulin-induced hypoglycemia or physiological responses to hypoglycemia. Since ODC is considered an indicator of growth stimulation, these results suggest that insulin or insulin-like peptides have a role in the regulation of brain development. PMID- 6243543 TI - Stimulation of guanosine 3',5'-monophosphate accumulation in anterior pituitary glands in vivo by synthetic luteinizing hormone-releasing hormone. AB - The in vivo effect of an iv injection of synthetic LHRH on cAMP and cGMP concentrations in the anterior pituitary gland of pentobarbital (31.5 mg/kg BW) injected proestrous rats and ovariectomized estradiol (10 micrograms)-primed rats was studied. At a specific time after an injection of LHRH or saline (as the control), the animals were sacrificed by microwave irradiation to the head. LHRH (100 ng/100 g BW) injection in the proestrous rat caused a significant increase in the cGMP level from 10-20 min associated with an increase in the serum LH level, whereas it exerted no effect on cAMP. No changes were observed in saline injected animals. In the ovariectomized estradiol-primed rat, LHRH (50 ng/100 g BW) injection performed under ether anesthesia also induced a significant elevation of cGMP level, after 5-10 min, in parallel with an elevation of serum LH level. Saline injection caused no change in cGMP. cAMP concentrations were increased 5-10 min after either LHRH or saline injection. These results suggest the involvement of a guanylate cyclase-cGMP mechanism in the mediation of LHRH action in the pituitary. PMID- 6243544 TI - Changes in adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate concentrations in the anterior pituitary and hypothalamus during the rat estrous cycle and effects of administration of sodium pentobarbital in proestrus. PMID- 6243545 TI - Thyrotropin-releasing hormone-receptor interaction in GH3 pituitary cells. AB - The interaction between TRH and GH3 pituitary tumor cells was studied in monolayer cultures or membrane-containing fractions. In intact cells, the apparent dissociation constant (Kd) was approximately 10 nM, and the total number of binding sites was approximately 1.4 pmol/mg protein at temperatures of 0-37 C. In broken cell preparations, the number of sites occupied at saturating TRH concentrations was reduced by half when the temperature was increased from 0 to 30 C. Linear Scatchard plots were obtained under all conditions. The rate of dissociation of TRH was temperature dependent, and first order plots were nonlinear. The half-times for dissociation at 0 C were over 240 min in cells and membranes, while at 37 C, the half-time values were 24 min (cells) and less than 0.5 min (membranes). Identical dissociation kinetics were obtained by dilution alone or dilution with excess unlabeled hormone. When cultures which had been incubated with TRH were lightly fixed with glutaraldehyde, dissociation at 37 C became immeasurably slow. However, TRH dissociated immediately when sodium dodecyl sulfate, ethanol, or acetone was added, indicating that the tripeptide was not covalently coupled to cell proteins. The data indicate that binding of TRH to high affinity GH3 receptors is not cooperative, and that the majority of TRH bound after short incubations is dissociable. PMID- 6243546 TI - Calcium dependence of steroid and guanine 3',5'-monophosphate induction of germinal vesicle breakdown in Rana pipiens oocytes. PMID- 6243547 TI - Oxytocin receptors and parturition. I. Control of oxytocin receptor concentration in the rat myometrium at term. AB - Rat myometrium exhibited a marked rise in the concentration of oxytocin (OT) receptors during parturition. The elevation began several hours before labor, was maximal during labor, and declined several hours later. In the perinatal period, the change in OT receptor concentration was proportional to the ratio of plasma estradiol to progesterone levels. Several hours before the increase in OT receptor concentration, there was a proportional increase in estrogen receptor concentration in both the cytosol and nuclear fractions of the myometrium. In view of the known action of estrogens in increasing the concentration of OT receptors in rat uterus, we propose that the following sequence of events occurs in the initiation of labor in the rat. The decline in serum progesterone permits estradiol to stimulate the synthesis of estrogen receptors in the myometrium. This increased concentration of estrogen receptors and their occupancy by estradiol stimulates the appearance of more OT receptors, which then trigger labor by interacting with circulating OT. PMID- 6243548 TI - Oxytocin receptors and parturition. II. Concentrations of receptors for oxytocin and estrogen in the gravid and nongravid uterus at term. AB - It has been postulated that intrauterine volume plays a role in the timing of parturition. In previous studies we found that the onset of parturition in the rat was associated with marked increases in the concentrations of receptors for estrogen and oxytocin in the myometrium. To determine the effects of intrauterine volume on the concentrations of these myometrial receptors, we compared receptor levels in gravid and nongravid uterine horns from unilaterally pregnant rats at or near the time of parturition. Myometria from gravid horns contained substantially greater concentrations of DNA and protein per horn than did myometria from the contralateral nongravid horns. The amounts of receptors per horn for estrogen in the nuclear and cytosol fractions and for oxytocin were 7.5, 5.2, and 4.5 times greater, respectively, in myometria from gravid horns. However, the concentration of receptors per cell was the same in gravid and nongravid horns at or near parturition. These results suggest that uterine stretch causes hyperplasia and hypertrophy of the myometrium, indicative of more DNA and protein per gravid horn than nongravid horn. The sharp rise in concentration per cell of receptors for estrogen and oxytocin occurring about the time of labor, however, appears to be induced by hormonal and not physical factors. PMID- 6243549 TI - Oxytocin receptors and parturition. III. Increases in estrogen receptor and oxytocin receptor concentrations in the rat myometrium during prostaglandin F2 alpha-induced abortion. PMID- 6243550 TI - Adenosine 3',5'-monophosphate-independent protein kinase activities in the bovine adrenal cortex cytosol. PMID- 6243551 TI - Release of growth hormone from purified somatotrophs: interrelation between Ca++ and adenosine 3',5'-monophosphate. AB - cAMP is thought to be an essential intracellular mediator in the release of GH from somatotrophs. Ca++ is required in the incubation medium to elicit GH release in vitro. We have carried out studies using a purified preparation of rat somatotrophs to see whether the Ca++ requirement procedes or follows the accumulation of cAMP induced by prostaglandin E2 (which increases adenylate cyclase activity) and 3-isobutyl-1-methylxanthine (a phosphodiesterase inhibitor). Incubation of somatotrophs in low Ca++ medium (less than 85 microM) abolished the release of GH induced by the two secretagogues, while the increase in intracellular cAMP was actually augmented. Thus, Ca++ is required in the incubation medium to express the action of intracellular cAMP. PMID- 6243552 TI - Ascorbic acid transport by isolated bovine adrenal cortical cells. AB - Viable, ACTH-sensitive, bovine adrenal cortical cells have the ability to accumulate [1-14C]ascorbic acid. Transport of the vitamin displays saturation kinetics (Km = 16.6 microM), requires Ca2+, and is inhibited maximally by ACTH at the same concentrations of the hormone necessary for maximal stimulation of steroidogenesis. Despite the transport of quantities of radioactive ascorbate amounting to approximately 25% of the total intracellular pool, no change in the ascorbate concentration in the cells can be detected by chemical methods. Transport of the vitamin is apparently a membrane carrier-mediated exchange process, since although intracellular ascorbate concentrations are 60- to 90-fold higher than those in the incubation medium, accumulated label can only be displaced when the cells are incubated in the presence of unlabeled ascorbic acid or metabolic inhibitors. Furthermore, ACTH fails to deplete ascorbic acid from [1 14C]ascorbate-loaded cells. It is hypothesized that the vitamin exists in two pools only one of which can be depleted by ACTH. This ACTH-depletable pool is no longer present in the isolated cell. In fact, as much as 66% of the ascorbic acid is lost from rat adrenals incubated for 15 min post adrenalectomy. The remaining pool of adrenal ascorbate is not depleted by ACTH and is also maintained against a concentration gradient. PMID- 6243553 TI - A mechanism for adenosine 3',5'-monophosphate regulation of vasopressin secretion. AB - The actions of cAMP released from neurohypophysial tissue may have an important role in regulating calcium fluxes and determining the state of activation of the neurosecretory nerve endings. PMID- 6243554 TI - Binding of thyroid hormones in vivo by hepatic nuclei of Rana catesbeiana tadpoles. AB - Thyroid hormone is essential for amphibian metamorphosis, and tadpoles develop responsiveness to exogenous T4 and T3 during the premetamorphic stage of development. The present studies were performed to investigate the receptors concerned with the initiation of this response. Premetamorphic tadpoles (stages VII-XV of Taylor and Kollros) were injected ip with [125I]T3 or [125I]T4 (0.001 10 nmol/tadpole). Twenty-four hours later, liver and serum were obtained, and organic 125I in liver nuclei and serum (shown to be unchanged hormone) was measured. Saturable binding sites for both T3 and T4 were present in the liver nuclei. Analysis of binding data indicated for T3 a mean value for Kd of 1.6 x 10(-12) M (moles of free T3 per liter plasma) and a mean value for maximum binding capacity of 0.1 ng/mg DNA. For T4, the mean Kd was 3.9 x 10(-15 M, and the mean maximum binding capacity was 0.5 ng/mg DNA. It was estimated that a significant fraction of these sites was not normally occupied by endogenous hormone. Properties of the T3-binding sites were similar in tadpoles at stages X and XV. Stable T4 and the acetic and propionic acid analogs of T3 competed with [125I]T3 for the sites almost as readily as did stable T3. The acetic acid analog of T4, D-T4, 3,5-diiodothyronine, and rT3, less active analogs, were relatively poor competitors. Binding of T3 to saturable but not to non-saturable nuclear binding sites was reduced in tadpoles kept at 4 C. On the basis of these findings, it is suggested that these nuclear binding sites are thyroid hormone receptors. PMID- 6243555 TI - Neural lobe of pituitary modulates corticotropin release in the rat. AB - The hypothesis was tested that the neural lobe of the pituitary may modulate the release of anterior pituitary hormones. The neural lobe of anesthetized lactating rats was electrically stimulated at 30 Hz (5 sec on and 5 sec off) for 3 min while taking blood samples for RIA of ACTH. Plasma ACTH increased within 3 min by 22 +/- 9% (average +/- SEM; P less than 0.025) in intact rats and by 38 +/- 17% (P less than 0.025) in rats where the nerve supply to the median eminence and neural lobe was interrupted. Electrical stimulation of the anterior pituitary was ineffective. No significant changes in plasma ACTH were observed in rats with coagulated hypophysial portal vessels or in Brattleboro rats with congenital diabetes insipidus. Apparently, neither peripheral plasma vasopressin (estimated at 150 microU/ml maximum) nor intermediate lobe ACTH could account for the observed rise in ACTH. Results suggest a vasopressin dependent modulation of ACTH release by the neural lobe, mediated either by axon collaterals to the median eminence or by a vascular interconnection between posterior and anterior pituitaries. PMID- 6243556 TI - Purification and characterization of mammary myoepithelial and secretory cells from the lactating rat. AB - Myoepithelial and secretory cells from the mammary gland of the lactating rat have been isolated, purified, and characterized. Mammary tissue was dissociated with collagenase into basket-like networks of myoepithelial cells and single secretory cells. Because of their larger size, the myoepithelial cell networks could be separated from other mammary and blood cells by differential centrifugation. Isolated secretory cells were purified by isopycnic centrifugation in 25% bovine serum albumin. The purified myoepithelial and secretory cells were viable, as shown by the incorporation of 32P into distinct macromolecules that were separable by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Both myoepithelial and secretory cells retained their characteristic morphology after isolation and purification, as shown by light, transmission, and scanning electron microscopies. The isolated myoepithelial cells were unique and, thus, distinguishable from other mammary cells in a number of respects; they 1) contracted in response to the addition of oxytocin, 2) bound [3H]oxytocin specifically, 3) accounted for the content of alkaline phosphatase and [Na+ + K+]ATPase in mammary tissue, and 4) reacted specifically with antiserum prepared against purified myoepithelial cells. The purified secretory cells were unique in possessing glucose-6-phosphate dehydrogenase activity. The different cell markers not only gave independent estimates of the purity of the cell fractions, but they also may be helpful in identifying mammary cells in stages of differentiation and neoplastic transformation. PMID- 6243557 TI - Studies on cyclic nucleotides in the adrenal gland. X. Effects of adrenocorticotropin and prostaglandin on adenylate cyclase activity in the adrenal cortex. AB - Effects of ACTH and prostaglandin E1 (PGE1) on adenylate cyclase activities in the zona glomerulosa (the capsular fraction) and the zona fasciculata-reticularis (the decapsulated fraction) from rat adrenocortical glands have been studied. Stimulation by ACTH of adenylate cyclase activity was observed in both the capsular and decapsulated fractions in a similar dose-dependent manner. PGE1 only stimulated adenylate cyclase activity in the capsular fraction. The maximal stimulations induced by ACTH and PGE1 were additive on the capsular enzyme. A prostaglandin antagonist, polyphloretin phosphate failed to inhibit ACTH stimulation of adenylate cyclase at a concentration which completely blocked the effect of PGE1. [3H]PGE1 bound to subcellular fractions of both the capsular and decapsulated fractions of the gland. These results suggest that the capsular fraction possesses receptors for PGE1 coupled to the adenylate cyclase system which are distinct from those for ACTH. On the other hand, PGE1 receptors in the decapsulated fraction seem not to be coupled to the adenylate cyclase system. PMID- 6243558 TI - Augmentation by chlorpropamide of 1-deamino-8-D-arginine vasopressin-induced antidiuresis and stimulation of renal medullary adenylate cyclase and accumulation of adenosine 3',5'-monophosphate. AB - The effect of chlorpropamide was determined in Brattleboro diabetes insipidus (DI) rats that were injected with 1-deamino-8-D-arginine vasopressin (dDAVP). Chlorpropamide augmented the antidiuretic responses to 0.78 and 1.56 ng dDAVP but not to larger doses. In an effort to explain this observation we investigated the effect of chlorpropamide on renal medullary adenylate cyclase activation by dDAVP and on phosphodiesterase activity. We found that the injection of chlorpropamide increased adenylate cyclase activation by dDAVP added in vitro to renal medullary cell membrane preparations from Brattleboro DI rats but had no effect on phosphodiesterase activity. When kidneys from Brattleboro DI rats, treated and not treated with chlorpropamide, were perfused in vitro, we found that 10(-4) M dDAVP increased the concentration of cAMP in comparison to untreated and chlorpropamide-treated groups, and that chlorpropamide plus dDAVP resulted in a greater concentration of renal cAMP than was found with dDAVP alone. We believe that treatment with chlorpropamide increases dDAVP-stimulated renal medullary adenylate cyclase activity without altering phosphodiesterase activity and that this leads to increased renal cAMP concentrations. This, in turn, causes an augmented antidiuresis in response to dDAVP. PMID- 6243559 TI - Effects of antibody to renal plasma membrane on urinary excretion of adenosine 3',5'-monophosphate and phosphate induced by parathyroid hormone infusion in rats. AB - Studies were made on the effects of pretreatment of rats with antibody to renal cortical plasma membrane (anti-RPM) on the urinary excretion of cAMP and phosphate induced by infusion of parathyroid hormone (PTH). With PTH infusion, the increase in the urinary excretion of cAMP and phosphate were not parallel. Infusion of 1-40 mg anti-RPM inhibited PTH-induced increase in urinary phosphate excretion but not the increase in urinary cAMP. Infusion of 100 mg of anti-RPM inhibited PTH-induced increases in the excretion of both substances. Infusion of nonimmunized rabbit immunoglobulin (IgG; normal IgG) did not affect PTH-induced increases in the excretion of either cAMP or phosphate. In vitro in isolated renal tubules, with 10 mg/ml anti-RPM, the increases in cAMP content induced by PTH were significantly less than those seen with lower concentrations of this antibody or with normal IgG. PMID- 6243560 TI - Effects of high potassium diet on angiotensin II receptors and angiotensin induced aldosterone production in rat adrenal glomerulosa cells. PMID- 6243561 TI - Pituitary-adrenal response in neonatal rats. PMID- 6243562 TI - Action of detergents on 3H-dihydroergokriptine binding and localization of alpha adrenoceptors in synaptosomal membranes. AB - 3H-dihydroergokriptine (3H-DHE) binding was carried out in synaptosomal membranes from basal ganglia of the cat. A single type of binding site with Kd 3.7 nM, Hill number = 0.95 and Bmax = 1000 pmol/g protein was found. 3H-DHE bound to alpha adrenoceptors and not to serotonin or dopamine receptors. At very low concentrations, some detergents enhanced binding, but at higher concentrations of those used (Triton X-100, Nonidet P-40, deoxycholate and digitonin), inhibited the binding of 3H-DHE. After binding to the membrane protein, the 3H-DHE-receptor complex was stable to the action of Triton X-100. At concentrations of Triton X 100. At concentrations of Triton X-100 (0.1--0.2%). in which only the presynaptic membrane disintegrated, the 3H-HDE specific radioactivity was reduced. With a more drastic treatment that disintegrated the postsynaptic membrane, 3H-DHE binding was further reduced. These results suggest that alpha-adrenergic receptors may be localized at both the pre- and postsynaptic membranes of central synapses. PMID- 6243563 TI - Synaptic transmission of vasoconstrictor nerves in rabbit basilar artery. PMID- 6243564 TI - Inhibitory action of adenosine and adenosine analogs on neurotransmission in the olfactory cortex slice of guinea pig - structure-activity relationships. AB - The postsynaptic potential (PSP) was recorded from thin slices of the olfactory cortex of the guinea pig. Application of adenosine and adenine nucleotides such as 5'-ATP, 5'-ADP and 5'-AMP in the incubation medium, depressed the amplitude of the PSP without altering the presynaptic fiber potential. The other purine and pyrimidine derivatives had no inhibitory effect. The inhibitory action of adenosine and adenine nucleotides on the PSP were manifest at concentrations of 5 microM-1 mM. Adenosine, 5'-ATP, 5'-ADP and 5'-AMP were equipotent in evoking depression of PSPs. Inhibition occurred within 10-20 sec after administration of the agents and the depressant effect disappeared rapidly after the removal of the compounds from the medium. Theophylline reversed and prevented the inhibition produced by adenosine and adenine nucleotides. To test the structure-activity relationships of these compounds, adenosine analogs and adenine nucleotide derivatives were applied to the medium. The 6-aminopurine riboside (adenosine radical) was found to be essential for inhibitory action on the PSP. Among adenosine analogs, the presence of at least one hydrogen atom in the amino group at the 6-position of the purine, and the OH group at the 2'-position of the ribose was essential for inhibitory activity. PMID- 6243565 TI - The effects of amrinone on contractility, Ca2+ uptake and cAMP in smooth muscle. AB - Amrinone, a known positive inotropic agent in the heart, was found to cause a dose-dependent (10--100 micrograms/ml) inhibition of norepinephrine (NE) or high K+-induced contractions of rabbit aorta. Amrinone also inhibited carbachol or high-K+-induced contractions of guinea-pig taenia coli. Neither total tissue 45Ca uptake nor the rate of 45Ca uptake induced by 80 mM K+ in rabbit aorta was altered by pretreatment with amrinone. On the other hand, a similar pretreatment with amrinone inhibited NE (10(-6) or 10(-5) M) induced tissue 45Ca uptake. Amrinone (100 micrograms/ml) caused about a 70% increase in cAMP concentration over resting levels. It is concluded that amrinone causes a nonspecific inhibition of smooth muscle contractility by acting probably at multiple sites to decrease the availability of Ca2+ required for activation. One or more of these mechanisms may involve cAMP. PMID- 6243566 TI - Di-isopropyl phosphofluoridate-induced antinociception: possible role of endogenous opioids. AB - Di-isopropyl phosphofluoridate (DFP, 0.1--1.5 mg/kg, s.c.) produced antinociception in rats as measured by the hot plate test. Naloxone reduced DFP induced antinociception but did not affect the attenuated locomotor activity or hypothermia produced by DFP. Animals rendered tolerant to the antinociceptive action of morphine failed to exhibit cross tolerance to the antinociceptive action of DFP. Morphine- and DFP-induced antinociceptive states were antagonized by MR 2266 and GPA 1843, the (-)-isomers of 5,9 alpha-Diethyl-2-(3-furylmethyl) 2'-hydroxy-6, 7-benzomorphan and -2-allyl-2'-hydroxy-9 beta-methyl-5-phenyl-6, 7 benzomorphan hydrochloride, respectively; the corresponding (+)-isomers, MR 2267 and GPA 1847, did not antagonize the antinociceptive state produced by DFP or morphine. These results suggest that DFP-induced antinociception may be mediated via the release of endogenous opioids; however, this could occur at sites different from those concerned with morphine tolerance. PMID- 6243567 TI - Paradoxical effect of naloxone on nitrous oxide analgesia in man. AB - The effect of naloxone on nitrous oxide analgesia in man has been investigated. The paradoxical response so obtained indicates the possibility of a dural system mediating the pain response in man. These results support previous animal experiments indicating that nitrous oxide analgesia is mediated by the opiate receptors. PMID- 6243568 TI - Decreased number of beta-adrenoceptors in cerebral cortex of hypothyroid rats. AB - The influence of thyroid hormone deficiency on beta-adrenoceptors in the rat cerebral cortex was investigated using the 3H-dihydroalprenolol binding assay. The maximal number of binding sites (Bmax) and the dissociation constants (KD) were determined in the brain tissue from euthyroid animals and from rats made hypothyroid by feeding 6-propyl-2-thiouracil. Hypothyroidism resulted in a 37% decrease in beta-adrenoceptor density (Bmax). The dissociation constants (KD) of both groups were not significantly different. PMID- 6243569 TI - Adrenergic receptors of cerebral microvessels. PMID- 6243570 TI - Transformation is an alternative to normal skeletal muscle development. PMID- 6243571 TI - Senescent human diploid cells (WI-38). Attempted induction of proliferation by infection with SV40 and by fusion with irradiated continuous cell lines. PMID- 6243572 TI - Role of silicon in diatom metabolism. X. Polypeptide labelling patterns during the cell cycle, silicate starvation and recovery in Cylindrotheca fusiformis. PMID- 6243573 TI - The purification of a respiratory oxidase complex from Escherichia coli. PMID- 6243574 TI - Ligand-induced change in the radius of gyration of cAMP receptor protein from Escherichia coli. PMID- 6243575 TI - A rapid procedure for purifying a restriction endonuclease from Thermus thermophilus (Tth I). PMID- 6243576 TI - Protection against exonuclease III digestion. A new way to investigate protein DNA interactions. PMID- 6243577 TI - Amino acid sequences of active-site histidine peptides from rabbit muscle phosphoglycerate mutase. PMID- 6243578 TI - Folic acid increases the cAMP binding activity of Dictyostelium discoideum cells. PMID- 6243579 TI - Role of different regions of ribosomal proteins L7 and L10 in their complex formation and in the interaction with the ribosomal 50 S subunit. PMID- 6243580 TI - Calcium uptake by cytochrome oxidase vesicles. PMID- 6243581 TI - A fluorescent 3'-ADP-analog: interaction with oxidative phosphorylation and the adenine nucleotide carrier. PMID- 6243582 TI - Rat mammary gland ATP-citrate lyase is phosphorylated by cyclic amp-dependent protein kinase. PMID- 6243583 TI - Rapid reversible inactivation of fructose-1,6-bisphosphatase in Saccharomyces cerivisiae by glucose. PMID- 6243584 TI - Cell cycle-dependent alterations of the two types of ribonucleases H in L5178y cells. PMID- 6243585 TI - On the fidelity of transcription by Escherichia coli RNA polymerase. PMID- 6243587 TI - The precocious appearance and activation of an adenylate cyclase in a rapid developing mutant of Dictyostelium discoideum. PMID- 6243586 TI - 5'-nucleotidase--adenylate cyclase relationships in mouse thymocytes. A re evaluation of the effects of concanavalin A on cyclic AMP levels. PMID- 6243588 TI - (D-Ala2, N-Val5) enkephalinamide and (D-Met2, N-Val)5 enkephalinamide. Two potent agonists of opiate and enkephalin receptors. PMID- 6243589 TI - Molecular forms of acetylcholinesterase in the chick visual system. Collagenase released 21.5 S and 16.5 S species. PMID- 6243590 TI - The presence of a Na+ATPase activity associated with mammalian brain microsomal fractions. PMID- 6243591 TI - Isolating the elusive islet. AB - The lack of a technique that allows mass isolation of intact, viable human islets is part of the reason that islet transplantation has not become available to the human diabetic. This report outlines the history of islet isolation and presents two new technical modifications that have been developed in the dog. Many of the current problems in islet isolation are presented, including the difficulty in obtaining enough human pancreatic tissue with minimal warm-ischemia time; inadequate distention of the pancreas to provide sufficient disruption for maximal enzymatic reaction to release intact islets; inefficient chopping methods; the use of collagenase of variable composition; different digestion methods for obtaining isolated islets; and inefficient methods for separating and purifying the islets from the ductal, acinar, and fibrous components. The first new modification involves distention of the dog pancreas through the venous system of the gland rather than the ductal system. This results in improved intralobular disruption, which improved the yield of isolated dog islets by permitting more efficient collagenase digestion. The second new modification eliminates the concept of isolating intact islets: the dog pancreas is digested by trypsin to a single-cell preparation that is partially purified by Ficoll gradients; further purification of the endocrine cells results from selective aggregation using rotational culture. This process produces pseudoislets that contain all the islet cell types and can be kept in culture for up to 4 wk, releasing their hormones in response to appropriate stimuli. These modifications may assist in the struggle to isolate the elusive human islet for safe and effective islet transplantation in the diabetic patient. PMID- 6243592 TI - Human colonic adenylate cyclase. Stimulation of enzyme activity by vasoactive intestinal peptide and various prostaglandins via distinct receptor sites. AB - The effects of meclofenamic acid on basal and hormone-stimulated adenylate cyclase in human colonic mucosa were tested. It is shown that meclofenamic acid is a relatively specific inhibitor of the stimulatory action of prostaglandins on the level of mucosal adenylate cyclase. This compound did not inhibit significantly the effects of vasoactive intestinal peptide (VIP) on the human enzyme system. VIP18-28 did not act as a partial agonist and did not inhibit the response to the intact VIP. Our studies suggest the existence of distinct receptor sites for both secretagogues (VIP and prostaglandins) in human colonic mucosa. PMID- 6243593 TI - Asking patients to switch clinics. PMID- 6243594 TI - Chromatographic and electrophoretic characterization of melanocyte-stimulating substances in the duck pituitary. PMID- 6243595 TI - Control of juvenile hormone biosynthesis during the reproductive cycle of a viviparous cockroach. III. Effects of denervation and age on compensation with unilateral allatectomy and supernumerary corpora allata. PMID- 6243596 TI - Recurrence of metastatic trophoblastic disease after negative, plasma human chorionic gonadotropin beta-subunit assay. PMID- 6243597 TI - Actinomycin D toxicity in the treatment of trophoblastic disease: a comparison of the five-day course to single-dose administration. PMID- 6243598 TI - Tumor antigenicity and the immune system in gynecological cancer: a review. PMID- 6243599 TI - Effect of cyclic adenosine-3',5'-monophosphate on the simultaneous synthesis of beta-galactosidase and tryptophanase in Escherichia coli. AB - When inducing simultaneously beta-galactosidase and tryptophanase in a batch culture either the synthesis of tryptophanase or of both enzymes is decreased due to an insufficient cAMP concentration. The addition of this nucleotide can overcome this decrease. In a continuous culture both enzymes are synthesized at the maximum rate, as the amount of cAMP produced during carbon limitation of growth is probably sufficient for the simultaneous synthesis of both enzymes. In the beta-galactosidase hyperproduction mutant cultivated continuously the level of beta-galactosidase markedly decreases when tryptophanase is simultaneously induced. Also this decrease is caused by cAMP insufficiency and can be overcome by increasing its concentration. cAMP is thus an important regulatory factor of both enzymes and becomes a limiting factor in their simultaneous synthesis; a competition for this regulatory compound apparently occurs and probably also a different mutual affinity of the regulatory complex with the promoter site of the enzyme operons is involved. PMID- 6243600 TI - Streptococcal extracellular NAD+ nucleosidase. Characterization of changes occurring during purification. AB - Purification of streptococcal extracellular NAD+ nucleosidase is associated with changes of kinetic properties. A high-molecular weight component is required for a full activity of the enzyme. The component is not produced by bacteria and is present in the Todd-Hewitt cultivation medium, the beef-heart extract serving primarily as its source. In its effect on the enzyme this component can be replaced with bovine albumin. It follows from the time relationship of the NAD decomposition that the mechanism of the studied enzymic reaction is not hydrolytic. In addition to nicotinamide, a product of polymeric character is formed. PMID- 6243601 TI - Transport of basic amino acids and regulation of aspartate kinase activity in thialysine and L-canavanine resistant strains of Serratia marcescens. AB - Growth of Serratia marcescens was not inhibited by high concentrations of L lysine and its structural analogues, L-cancavanine and S-(2-aminoethyl)-L cysteine (thialysine). This insensitivity was not caused by deficient transport of basic amino acids, unlike in mutant strains of Escherichia coli having the same properties. The tested strains showed a lack of regulation at the aspartate kinase level toward L-lysine and thialysine. The data indicate great intraspecific variability for aspartate kinase regulation in S. marcescens. PMID- 6243603 TI - [Tabular instructions for differential diagnosis of polyneuropathies (author's transl)]. AB - Following a brief review of the nosological system a comprehensive table containing diseases in which polyneuropathies can occur is presented. The tables list the typical neurological syndrome, affections of other organ systems, diagnostical aids from history, clinical course and additional findings and finally the most important differential diagnoses and specific treatment. A list of diseases which show similar accentuation of polyneuropathy is added. PMID- 6243602 TI - Isolation of spermatozoa in vaginal contents by centrifugation in a colloidal silica gradient. AB - Human spermatozoa were separated from vaginal contents with epithelial cells by density gradient centrifugation in colloidal silica coated with polyvinylpyrrolidone. In this procedure spermatozoa were collected at a density range of 1.130 - 1.142 g/ml by centrifugation at 35 000 g for 1 h. PMID- 6243604 TI - The ultrastructure of benign and malignant fibrous histiocytomas. AB - Five benign histiocytomas of varying pattern and three malignant fibrous histiocytomas have been studied ultrastructurally. An essentially biphasic pattern of histiocytes and fibroblasts was present. In addition fibrohistiocytes, myofibroblasts and undifferentiated cells were present in some of the tumours. The histogenesis of this group of tumours is discussed. The value of electron microscopy in establishing the diagnosis in difficult cases is emphasized, but it is not considered useful in distinguishing benign from malignant cases. PMID- 6243605 TI - Cytophotometric investigation of the Feulgen-DNA content of cell nuclei of fibrous histiocytomas. AB - The cytophotometric determination of the Feulgen-DNA content of cell nuclei was performed on 72 fibrous histiocytomas. From the histograms, three variants of this neoplasm could be delineated and there was a fairly good correlation between the type of histogram and prognosis. With the exception of the benign dermal fibrous histiocytomas there was no correlation with the histological sub-types. PMID- 6243606 TI - Assessing the community care of chronic psychotic patients. AB - The placements, activity levels, and hospital admissions of 263 of the most severely mentally ill patients in a county continuing care program were studied over an 18-month period. The findings showed a major shift of patients from local locked facilities to independent living and a 33-per-cent drop in county hospital psychiatric admissions. But activity levels of many of the patients were well below therapists' expectations, with almost half doing little or nothing at 18 months. The authors conclude that essential services were provided for this group, but that their integration into the community was hampered by insufficient recreational and vocational activities. PMID- 6243607 TI - Building a network of aftercare services. AB - When a state hospital in New York began returning long-term psychiatric patients to community living in Westchester County in 1974, the staff of the hospital, local community mental health providers, administrators of a private proprietary home for adults that received many of the patients, and local citizens worked to develop an integrated system of aftercare services. The local mental health council served as the umbrella group for the coordination of the various providers and consumers. The council's aftercare committee investigated several troubling aspects of the deinstitutionalization process including patient selection, the program and staffing of the home, transportation for residents, the physical structure of the home, and its licensing. The authors report the committee's findings and resolutions of some of the problems, and discuss some of the financial difficulties of residents in the home. While some problems remain, the authors feel that the council structure was a crucial element in facilitating a coordinated network of aftercare services. PMID- 6243608 TI - Acute diarrheal infections in infants I. Bacterial and viral causes. PMID- 6243609 TI - Human red cell galactose-1-phosphate uridylyltransferase (EC 2.7.7.12). Electrophoretically determined polymorphism in Denmark and its use in paternity cases. AB - The electrophoretically detectable phenotypes of human red cell galactose-1 phosphate uridylyltransferase (GALT) were determined in 2,074 unrelated Danes. The gene frequencies were: GALT1 = 0.9233 and GALT2 = 0.0767. The segregation of phenotypes in 765 mother-child pairs was consistent with autosomal codominant inheritance. One apparent mother-child incompatibility with respect to phenotypes was observed which, however, appeared to be due to the segregation of a silent gene. The results of an investigation of 248 paternity cases are reported, and the application of the GALT polymorphism to paternity cases is discussed. PMID- 6243610 TI - Adjuvant effects of amorphous silica and of aluminium hydroxide on IgE and IgG1 antibody production in different inbred mouse strains. AB - The adjuvant effects of an amorphous silica (Aerosil) and of A1(OH)3 on primary and secondary IgE and IgG1 immune responses to small doses of OA were studied comparatively in BALB/c, C57BL, DBA/1, AKR, DBA/2 and SJL inbred mouse strains. During the primary response, all mouse strains produced both IgG1 and IgE antibodies when antigen was given with A1(OH)3, whereas only DBA/1, BALB/c and DBA/2 mice produced IgG1 and/or IgE antibodies when Aerosil was used as the adjuvant. A booster effect, higher than that obtained by A1(OH)3, was induced by Aerosil in all mouse strains. The adjuvant effect of Aerosil was more selectively directed to the production of IgE antibody. PMID- 6243611 TI - A multivariate factor analysis of the high plasma concentration of cyclic AMP in patients with chronic renal failure. AB - The concentration of cyclic AMP which is known as an intracellular mediator of hormone action increased in the plasma of patients with chronic renal failure (CRF). In the present study, the plasma concentration of cyclic AMP significantly correlated not only with serum, creatinine, and urea levels, but also with plasma PTH and glucagon in patients with CRF. Furthermore, plasma concentrations of PTH and glucagon correlated with the serum creatinine concentration to a significant extent. To discuss the cause of the increased cyclic AMP concentration in plasma of patients with CRF, multivariate analyses were carried out on the obtained clinical data from patients and normal subjects. In the factor analysis on the clinical data from 61 subjects, cyclic AMP, creatinine and BUN correlated with the first factor and PTH correlated with the second factor. The cumulative contribution ratio by the second factor was 76%. The results of the cluster analysis indicated that cyclic AMP, creatinine, and BUN formed a cluster and PTH glucagon made another cluster. These results suggest that the elevated plasma concentration of cyclic AMP in patients with CRF was mainly introduced not by overproduction but by the retention of cyclic AMP due to the decreased renal function. PMID- 6243612 TI - Peripheral neuropathy in dialysis patients. PMID- 6243613 TI - Improvements of motor response by means of hypnosis in patients with peripheral nerve lesions. PMID- 6243614 TI - Angiographic variant in juvenile nasopharyngeal angiofibroma. AB - A 17-year-old male with juvenile nasopharyngeal angiofibroma was found, on preoperative evaluation, to have a normal selective angiogram of the internal and external carotid artery system. Possible explanations for this variant include an atypical blood supply from the vertebral artery system, the thyrocervical trunks, or from an ascending pharyngeal artery that branched low from the external carotid artery. PMID- 6243615 TI - Noradrenergic inhibitory innervation of canine airways. AB - The inhibitory innervation of canine airways was examined in isolated trachealis strips and helical strips of airways having outside diameters of 5 and 1.5 mm. Exogenous norepinephrine (10-8 M to 10-3 M) did not alter resting tone but relaxed airways contracted by 10-5 M histamine. Relaxations produced by norepinephrine were antagonized by 10-6 M propranolol, demonstrating the presence of beta-adrenergic receptors. Trans-ural electric stimulation also inhibited contractions produced by histamine. These electrically induced relaxations were blocked by tetrodotoxin and were reduced in magnitude by propranolol, indicating the involvement of a sympathetic neural mechanism. The inhibitory response to electric stimulation was attenuated in airways from catecholamine-depleted dogs and abolished in four of nine catecholamine-depleted airways pretreated with propranolol. Exogenous tyramine (10-5 M) also relaxed histamine-induced contractions, and this effect was blocked by propranolol or catecholamine depletion. The study showed that beta-adrenergic receptors from the trachea to 1.5-mm airways are innervated and that this sympathetic system constitutes the primary inhibitory innervation of airway smooth muscle in the dog. PMID- 6243616 TI - Analysis of rebreathing measurements of pulmonary tissue volume in pulmonary edema. AB - A rebreathing method (usood volume (VTPC) was evaluated in 13 dogs. In seven, pulmonary edema was induced by oleic acid injection. Six dogs served as controls. Values of VTPC calculated by three algorithms were compared to postmortem lung water. The first algorithm uses the C18O intercept to determine time 0 and all data to construct the alveolar disappearance curves. The second uses the beginning of inspiration as time 0. The last uses data only during the last third of expiration. The best correlation (r = 0.90) between VTPC and total lung water was obtained utilizing the first algorithm. In the control animals, mean VTPC was 188 ml, and in the edema dogs was 278 ml. Mean VTPC for all dogs was 96 +/- 14% of total lung water using the first algorithm. Another algorithm (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 44: 782-795, 1978) was evaluated inthe edema dog group. This method gave values of VTPC 53% higher than those obtained by the first algorithm. PMID- 6243617 TI - Bluetongue and epizootic hemorrhagic disease virus isolation from vertebrate and invertebrate hosts at a common geographic site. AB - One serotype of bluetongue virus (BTV) and two serotypes of epizootic hemorrhagic disease virus (EHDV) were isolated from vertebrate and invertebrate hosts on a farm in Colorado. The isolations were from blood samples collected a week apart from a dairy heifer with stomatitis and laminitis; EHDV serotypes 1 and 2 were isolated from the first blood sample, and BTV serotype 13 and EHDV serotype 1 were isolated from the second. Antibodies to EHDV and BTV were detected in the serum from this heifer. Both EHDV serotypes and BTV serotype 13 were isolated from pools of female biting gnats (Culicoides variipennis) that had not had a recent blood meal. The BTV insect isolate was biologically transmitted by female gnats from an infected donor sheep to a recipient host sheep. Culicoides variipennis was the predominant insect collected during three nights of light trap captures at the farm. PMID- 6243618 TI - Carbamyl phosphate synthetase A of Neurospora crassa. AB - Carbamyl phosphate synthetase A of Neurospora crassa was partially purified from mitochondrial extracts. It is an extremely unstable enzyme (t 1/2 = 45 min at 25 detrees C) made up of two unequal subunits. The native enzyme has a molecular weight of approximately 175,000, and the large subunit has a molecular weight of about 125,000. Both the native enzyme and its large subunit are quite asymmetric, as revealed by slow sedimentation in sucrose gradents (7.3S and 6.6S, respectively). The small subunit has not been identified physically as a separate entity. The denaturation of the native, glutamine-dependent activity is correlated with dissociation of subunits, the larger of which retains a more stable, ammonia-dependent activity. Neither substrates nor any other agents except glycerol or polyethylene glycol appreciably stabilized the glutamine dependent activity. Kinetic studies showed the native enzyme to have a Km for glutamine of about 0.16 mM, and a Km for NH4Cl of about 16 mM, at the optimal pH, 8.0. The enzyme, using either N donor, has a K+ requirement for activity, for which NH4+ can substitute. The glutamine leads to glutamate reaction, which requires the small subunit, also requires the large subunit and all reaction substrates for optimal activity. Other evidences of subunit interaction are the greater activity of the native enzyme, as opposed to the large subunit, with low concentrations of adenosine 5'-triphosphate-Mg2+, and in the stimulation of the ammonia-dependent activity of the native enzyme by glycine. Curiously, although the enzyme's role in biosynthesis is confined to the arginine pathway, it is completely indifferent to arginine or its precursors as feedback effectors or activators. The enzyme is compared with carbamyl phosphate synthetases of other organisms. PMID- 6243619 TI - Mechanism of the antibiotic action pyocyanine. AB - Exposure of Escherichia coli growing in a rich medium to pyocyanine resulted in increased intracellular levels of superoxide dismutase and of catalase. When these adaptive enzyme syntheses were prevented by nutritional paucity, the toxic action of pyocyanine was augmented. The antibiotic action of pyocyanine was dependent upon oxygen and was diminished by superoxide dismutase and by catalase, added to the suspending medium. Pyocyanine slightly augmented the respiration of E. coli suspended in a rich medium, but greatly increased the cyanide-resistant respiration. Pyocyanine was able to cause the oxidation of reduced nicotinamide adenine dinucleotide, with O2- production, in the absence of enzymatic catalysis. It is concluded that pyocyanine diverts electron flow and thus increases the production of O2- and H2O2 and that the antibiotic action of this pigment is largely a reflection of the toxicity of these products of oxygen reduction. PMID- 6243620 TI - Precursor in cotranslational secretion of diphtheria toxin. AB - By extracellular labeling of peptides of intact Corynebacterium diphtheriae, followed by fractionation of the cells and chain completion by isolated polysomes, it is shown that diphtheria toxin is formed and secreted cotranslationally by membrane-bound polysomes; free polysomes from none. Moreover, when the chains on these polysomes were completed in vitro, in the absence of membrane they were found to include not only diphtheria toxin of a molecular weight of 62,000, but also a larger precursor of a molecular weight of 68,000. The precursor was identified by several properties: immune precipitation; conversion into toxin fragments A and B; adenosine diphosphate ribosyl transferase activity after activation with trypsin; and cleavage to 62,000 daltons by membrane enzymes. The precursor yields an N-terminal A fragment with a broadened molecular weight distribution, compared with that from authentic toxin, thus supporting the expectation that the extra segment of the precursor is N terminal. PMID- 6243621 TI - Regions of broad-host-range plasmid RK2 which are essential for replication and maintenance. AB - The sites of cleavage on the map of the broad-host-range plasmid RK2 (56 kilobases) were determined for the BglII, PstI, and SmaI restriction enzymes, and the determinants for tetracycline and ampicillin resistance were localized. The cleavage sites were clustered at or near the drug resistance genes. To localize regions required for plasmid replication and maintenance in Escherichia coli, we deleted nonessential regions of RK2 by partial digestion with the restriction endonuclease HaeII to produce small derivatives. The smallest stable replicon obtained contained five HaeII fragments of RK2 which total 5.4 kilobases. These fragments were derived from three regions of RK2 that are separated from each other by antibiotic resistance genes. One of these HaeII fragments (0.75 kilobases) has the properties expected of the origin of replication. The outer four fragments, located in two separate regions of RK2, were found to provide, in trans, functions that permit the replication of the HaeII fragment carrying the origin of the replication. These results indicate that at least two plasmid encoded genes, capable of acting in trans, and a replication origin are required for RK2 replication and maintenance. PMID- 6243622 TI - Characterization of chimeric plasmid cloning vehicles in Bacillus subtilis. AB - Restriction endonuclease cleavage maps of seven chimeric plasmids that may be used for molecular cloning in Bacillus subtilis are presented. These plasmids all carry multiple antibiotic resistance markers and were constructed by in vitro molecular cloning techniques. Several of the antibiotic resistance markers were shown to undergo insertional inactivation at specific restriction endonuclease sites. Kanamycin inactivation occurred at the BglII site of pUB110 derivatives, erythromycin inactivation occurred at the HpaI and BclI sites of pE194 derivatives, and streptomycin inactivation occurred at the HindIII site of pSA0501 derivatives. A stable mini-derivative of pBD12 was isolated and characterized. By using these plasmids, we identified proteins involved in plasmid-coded kanamycin and erythromycin resistance. The properties and uses of these chimeric plasmids in the further development of recombinant deoxyribonucleic acid technology in B. subtilis are discussed. PMID- 6243623 TI - Deoxyribonucleic acid restriction and modification systems in Salmonella: chromosomally located systems of different serotypes. AB - With the use of four different phages, Salmonella strains representing 85 different serotypes were examined to determine their restriction-modification phenotype. They fell into one of three groups on this basis: group 1, those which lacked the common LT system; group 2, those in which only the LT system could be recognized; and group 3. those which possessed the LT system and at least one other system shown with some serotypes to be closely linked to serB. The specificity of the serB-linked restriction-modification system was unique for each serotype, but different strains of the same serotype expressed the same specificity. Two of the systems were shown to behave in genetic crosses as functional alleles of the S. typhimurium SB system. It is possible that these serB-linked restriction-modification systems constitute a large multiallelic series of genes extending throughout the Salmonella genus and Escherichia coli. We suggest that the division of the Salmonella into the three restriction modification groups may be significant in defining a "biological grouping" of the different serotypes within the genus which may ultimately be useful in describing the Salmonella species. From the genetic relatedness between the genes of some of the Salmonella restriction-modification systems with those of the E. coli systems, we deduce that the restriction endonuclases produced by the Salmonella serB-linked systems are of type 1. Determination of the nucleotide sequences of the recognition sites of the restriction endonucleases of selected Salmonella systems should further our understanding of specificity with these enzymes. PMID- 6243624 TI - Site-specific recombination between plasmids of Staphylococcus aureus. AB - Anomalous recombination between two similar but nonidentical, naturally occurring penicillinase plasmids, pI258 and pI524, leading to duplication and deletion of the beta-lactamase locus, is described. Physical mapping of these plasmids by heteroduplex and restriction analysis revealed that the beta-lactamase loci were homologous and in inverted orientation with respect to one another and that their respective locations were separated by a short region of homology. This intervening region of homology included one copy of a segment that was repeated on pI524 in inverted orientation at a distance of 2.2 kilobase pairs and contained a recognition sequence for a site-specific, rec-independent recombination function that caused reversible inversion of this segment on pI524. It is proposed that site-specific, intermolecular recombination involving this repeated sequence was responsible for the observed results. PMID- 6243625 TI - Purine-containing compounds, including cyclic adenosine 3',5'-monophosphate, induce fruiting of Myxococcus xanthus by nutritional imbalance. AB - Induction of Myxococcus xanthus fruiting by a number of different purine containing compounds, including cyclic adenosine 3',5'-monophosphate, is defective in a mutant resistant to 2,6-diaminopurine. Furthermore, the purine induced fruiting of wild-type cultures is uniquely blocked by a low concentration of added glycine. These results imply that different purine-containing compounds induce fruiting through a single mechanism involving nutritional imbalance. PMID- 6243627 TI - Genetic analysis of Escherichia coli mutants defective in adenylate kinase and sn glycerol 3-phosphate acyltransferase. AB - Complementation analysis with independently isolated plA and adk (adenylate kinase) mutants of Escherichia coli showed that all the mutants belong to the same complementation group. The results suggest that the adk (plsA) locus is the structural gene for adenylate kinase. PMID- 6243626 TI - Isolation and properties of calmodulin from Dictyostelium discoideum. AB - A calcium-dependent regulatory protein (calmodulin) was purified from vegetative amoebae of Dictyostelium discoideum. The properties of Dictyostelium calmodulin are similar but not identical to those of bovine brain calmodulin. Calmodulin activity was not detected in extracts of Saccharomyces cerevisiae or Escherichia coli. PMID- 6243628 TI - A stable plasmid carrying the yeast Leu2 gene and containing only yeast deoxyribonucleic acid. AB - The plasmid pSLe1 is a deletion derivative of the yeast-Escherichia coli hybrid plasmid pJDB219, obtained by HindIII digestion, ligation, and transformation directly into Saccharomyces cerevisiae. pSLe1 has only yeast sequences; it contains one of the inverted repeated sequences of plasmid 2muDNA and the LEU2 gene. pSLe1 is stably maintained in yeast cells without selective pressure. pSLe1 is about half as large as 2muDNA, but pSLe1 does not displace the normal 2muDNA. PMID- 6243629 TI - Cluster of mrdA and mrdB genes responsible for the rod shape and mecillinam sensitivity of Escherichia coli. AB - Two closely linked genes, mrdA and mrdB, located at ca. 14.2 min on the Escherichia coli chromosomal linkage map, seen to be responsible for the normal rod shape and mecillinam sensitivity of E. coli. The product of mrdA was concluded to be penicillin-binding protein 2, because mrdA mutations caused formation of thermosensitive penicillin-binding protein 2. The product of the mrdB gene is unknown. At 42 degrees, C, mutation in either of these genes caused formation of spherical cells and mecillinam resistance. Both mutations was recessive, and complementation, as detected in +-/-+ meroheterodiploids having the wild-type phenotype, provided strong evidence that the two mutations are in different complementation groups. P1 transduction suggested that the most plausible gene order is leuS-mrdA-mrdB-lip. The rodA mutation reported previously seems to be similar to the mrdB murations, but the identities of the two have not yet been proven. PMID- 6243630 TI - In vitro synthesis of Escherichia coli carbamoylphosphate synthase: evidence for participation of the arginine repressor in cumulative repression. AB - A deoxyribonucleic acid-directed in vitro system for the synthesis of Escherichia coli carbamoylphosphate synthase has been developed, and its properties have been studied. The system uses the deoxyribonucleic acid of a lambda phage carrying the car genes (lambdadcarAB) as template and mediates the synthesis of both subunits of the enzyme. This newly synthesized enzyme exhibits the properties of native carbamoylphosphate synthase. A study of the in vitro synthetic capacities of S-30 extracts from strains containing either a mutated or the wild-type allele of gene argR supports earlier suggestions, based on in vivo evidence, that the argR product is involved in cumulative repression of carbamoylphosphate synthase by arginine and the pyrimidines. Repression in vitro is as efficient as in vivo. In keeping with such observation it is shown that in vitro synthesis of carbamoylphosphate synthase is repressed by partially purified arginine repressor. Evidence was obtained which indicates that arginine repression of carbamoylphosphate synthase mainly operates at the level of transcription. This was based on the design of an in vitro transcription system for gene carA, the structural gene for the light subunit of carbamoylphosphate synthase. This system also allowed us to demonstrate that free arginine is the corepressor involved in carbamoylphosphate synthase repression. The present in vitro approaches, in addition to the information they have already provided, open new possibilities for further investigations on the mechanism of cumulative repression and, in particular, on the participation of pyrimidine end products in this regulatory mechanism. PMID- 6243631 TI - Cloning of replication, incompatibility, and stability functions of R plasmid NR1. AB - The region of R plasmid NR1 that is capable of mediating autonomous replication was cloned by using EcoRI, SalI, and PstI restriction endonucleases. The only EcoRI fragment capable of mediating autonomous replication in either a pol+ or a polA host was fragment B. SalI fragment E joined in native orientation with the part of SalI fragment C that overlapped with EcoRI fragment B, and also two contiguous PstI fragments of sizes 1.6 and 1.1 kilobases from EcoRI fragment B mediated autonomous replication. When these individual SalI fragments were cloned onto plasmid pBR313 or the individual PstI fragments were cloned onto plasmid pBR322, none of these single fragments could rescue the replication of the ColE1 like vectors in a polA host, even in the presence of a compatible "helper" plasmid derived from a copy mutant of NR1. In contrast to the results reported for closely related R plasmid R6, EcoRI fragment A of NR1 could not rescue the replication of ColE1 derivative RSF2124 in a polA(Am) mutant or in a polA(Ts) mutant at the restrictive temperature. Although capable of autonomous replication, EcoRI fragment B of NR1 (or smaller replicator fragments cloned from it by using other restriction enzymes) was not stably inherited in the absence of selection for the recombinant plasmid. When EcoRI fragment B was ligated to EcoRI fragment A of NR1, the recombinant plasmid was stable. Thus, EcoRI fragment A contained a stability (stb) function. The stb function did not act in trans since EcoRI fragment B was not stably inherited when a ColE1 derivative (RSF2124) ligated to EcoRI fragment A was present in the same cell. A cointegrate plasmid consisting of EcoRI fragment B of NR1 ligated to RSF2124 was also not stably inherited, whereas only EcoRI fragment B was unstable when both RSF2124 and EcoRI fragment B coexisted as autonomous plasmids in the same cell. The incompatibility gene of NR1 was shown to be located within the region of overlap between SalI fragment E and the PstI 1.1-kilobase fragment. A copy mutant of NR1 (called pRR12) was found to have greatly reduced incompatibility with NR1; this Inc- phenotype is cis dominant. PMID- 6243632 TI - Regulation of acetylcholine receptor by cyclic AMP. AB - In primary cultures of chick 11-day embryonic tissue a number of phosphodiesterase inhibitors were found to elevate acetylcholine receptor levels. Of these agents, Ro20-1724 was the most effective, elevating surface receptor content by 2-fold after 48 h of treatment. 8-Br-cAMP and cholera toxin, a natural activator of adenylate cyclase, mimicked the effect of Ro20-1724, while 8-Br-cGMP and dibutyryl cGMP had no effect. Cholera toxin, 8-Br-cAMP, and Ro20-1724 all increased the insertion rate of new receptor into the surface membrane without altering degradation. The enhanced insertion appears related to an actual increase in synthesis since total acetylcholine receptor was elevated by exposure to cholera toxin. In contrast, no change in creatine phosphokinase activity, myosin heavy chain content, or [35S] methionine incorporation into total cellular protein was observed during cholera toxin treatment. These results suggest that cAMP plays a role in the regulation of acetylcholine receptor. PMID- 6243633 TI - Dansylcadaverine inhibits internalization of 125I-epidermal growth factor in BALB 3T3 cells. AB - The binding and internalization of 125I-epidermal growth factor (125I-EGF) was studied in cultures of BALB 3T3 cells using a novel method that involved removal of cell-surface hormone by treatment with acetic acid under conditions that did not remove internalized hormone. In control cultures, 125I-EGF initially bound to its receptor on the plasma membrane and then was rapidly internalized. After 30 min, only 15% of the cell-bound hormone remained on the surface. In contrast, cultures treated with dansylcadaverine retained 82% of the cell-bound hormone on the cell surface. We propose that dansylcadaverine inhibits EGF internalization by preventing it from clustering in clathrin-coated pits. PMID- 6243634 TI - Isolation and chemical characterization of the major envelope glycoprotein of avian myeloblastosis virus. PMID- 6243635 TI - Affinity chromatographic purification and properties of flavokinase (ATP:riboflavin 5'-phosphotransferase) from rat liver. AB - Flavokinase (ATP:riboflavin 5'-phosphotransferase, EC 2.7.1.26) has been purified to apparent homogeneity from rat liver by affinity chromatography using flavinyl agarose beads (agarose-OCH2CONH(CH2)2NHCO(CH2)/N10-7,8-dimethylisoalloxazine). The specific activity of the pure enzyme is 9,900 units (nmol of FMN formed/h at 37 degrees C)/mg of protein, and reflects a one-step, 7000-fold purification. Flavokinase thus obtained, unlike previous preparations from mammalian sources, is free from contaminating phosphatase and FAD synthase. The purified enzyme rapidly loses activity upon storage but is stabilized by riboflavin and thiol protecting reagents. The apparent molecular weight, estimated by gel filtration on Sephadex G-100 and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, is 28,000 +/- 1,000. Flavokinase phosphorylates and/or is inhibited by a large number of riboflavin analogs; however, the physiologically important 8 alpha (amino acid)riboflavins are poorly accommodated. The strongly preferred phosphate donors are ATP and dATP. Both Zn2+ and Mg2+, as well as several other divalent cations, activate flavokinase, but Zn2+ yields greatest activity (1.8 times that with Mg2+). The pH optimum for activity with either Zn2+ or Mg2+ is approximately 9.3; at pH 7.0, the activity is 40% of that at the pH optimum. PMID- 6243636 TI - Inhibition by low density lipoproteins of mitogen-stimulated cyclic nucleotide production by lymphocytes. PMID- 6243637 TI - A high affinity agonist . beta-adrenergic receptor complex is an intermediate for catecholamine stimulation of adenylate cyclase in turkey and frog erythrocyte membranes. PMID- 6243638 TI - The chicken transferrin gene. Restriction endonuclease analysis of gene sequences in liver and oviduct DNA. AB - The organization of the chicken transferrin gene and its surrounding sequences was determined by a comparison of the restriction map of the cloned structural gene (double-stranded cDNA) with the map of the transferrin gene in genomic DNA. This analysis reveals a complex arrangement of the transferrin gene in which structural sequences are interrupted by a minimum of 6 intervening sequences, and span at least 10 kilobases in genomic DNA. Furthermore, comparison of the DNA from individual chickens of the same breed indicates considerable allelic diversity in the restriction sites for Eco RI, HindIII, and Bam HI. Quantitation of the number of transferrin genes by saturation hybridization confirms that both liver and oviduct DNAs contain only 1 transferrin gene/haploid complement, and, in addition, comparison of the restriction patterns obtained with DNA from these two tissues, as well as erythrocyte DNA, does not reveal any difference in the structural organization of the gene. We conclude that the distinct tissue specific transcriptional regulation of this gene by steroids and iron levels in the oviduct and liver cannot be explained either by a multiplicity of genes or by somatic reorganization of the gene. PMID- 6243639 TI - Characterization of a Mg2+-stabilized state of the (Na+ and K+)--stimulated adenosine triphosphatase using a fluorescent reporter group. AB - A Mg2+-induced change of the (Na+ and K+)-stimulated adenosine triphosphatase (Na+,K+)-ATPase) from Electrophorus electricus was investigated by kinetics and fluorescence techniques. Binding of Mg2+ to a low affinity site(s) caused inhibition of (Na+,K+)-ATPase activity, an effect which was antagonized by both Na+ and ATP. Mg2+ also caused inhibition of K+-dependent dephosphorylation of the enzyme without inhibiting either (Na+)-ATPase activity or Na+-dependent phosphorylation. Mg2+ also induced a 5 to 6% enhancement in the fluorescence intensity of enzyme labeled with the fluorescent sulfhydryl reagent, 2-(4 maleimidylanilino)naphthalene-6-sulfonate. As in the case of Mg2+ inhibition of activity, the affinity for Mg2+ as an inducing agent for this effect was significantly reduced by both Na+ and ATP, suggesting that the same change was being monitored in both cases. The Mg2+ effect was reduced by both Na+ and ATP, suggesting that the same change was being monitored in both cases. The Mg2+ effect was reduced in magnitude by ouabain and prevented by oligomycin, specific inhibitors of the enzyme. In addition, K+ (and cations that substitute for K+ in supporting activity) induced a 3 to 4% enhancement in fluorescence intensity in the presence of Na+, Mg2+, and ATP, although the K+ and Mg2+ effects appeared to be different on the basis of their excitation spectra. The K+ effect was inhibited by ouabain and occurred with a rate greater than the rate of turnover of the enzyme, permitting its involvement in the catalytic cycle. PMID- 6243640 TI - Linkage between self association and catalytic activity of Escherichia coli carbamyl phosphate synthetase. PMID- 6243641 TI - Apparent constants for the interaction of regulatory and catalytic subunit of cAMP-dependent protein kinase I and II. PMID- 6243642 TI - The role of calcium in the control of adrenal adenylate cyclase. Enhancement of enzyme activation by guanyl-5'-yl imidodiphosphate. PMID- 6243643 TI - Secretion of chondroitin SO4 by monolayer cultures of chick embryo chondrocytes. AB - Monolayer cultures of chick embryo tibial chondrocytes incorporate 35SO42- into chondroitin SO4 which is rapidly secreted from the cells into two extracellular pools. Part of the extracellular chondroitin SO4 is recovered in a soluble form in the culture medium, and the remainder is associated with the cell matrix from which it is released by isotonic trypsinization. At 38 degrees C labeled chondroitin SO4 appears in the cell matrix fraction within 5 min after addition of 35SO42- and in the culture medium fraction 15 min after 35SO42- is added. The intracellular pool of labeled chondroitin SO4 reaches a steady state level of 150 to 200 pmol of bound SO4 per 10(6) cells in 60 min, while the cell matrix and medium fractions increase at rates of 3 and 1 nmol of bound SO4 per h per 10(6) cells, respectively. After 4 h of labeling, less than 20% of the newly synthesized cell-associated chondroitin SO4 is in the intracellular fraction. By labeling cells for 15 min at 25 degrees C 80% of the cell-associated chondroitin 35SO4 is obtained in the intracellular fraction. This material is chased without lag into both the cell matrix fraction and the medium fraction. A mixture of NaF and NaCN, both at 30 mM, lowers the cellular ATP level to 15% of normal and blocks secretion of the intracellular chondroitin SO4 into both extracellular fractions. Colchicine at 10(-6) M gives a partial inhibition of both synthesis and secretion of chondroitinSO4. Sucrose density gradient sedimentation analysis of the intracellular chondroitin SO4 and the two extracellular fractions shows that all three fractions contain both a heavy and light proteoglycan fraction. The intracellular light proteoglycan fraction is secreted preferentially into the culture medium where it represents 30% of the total culture medium pool. The ratio of 6-sulfated GalNAc to 4-sulfated GalNAc in the heavy proteochondroitin SO4 fraction is approximately twice that found for the light fraction. PMID- 6243644 TI - Comparative study of oxygen and carbon monoxide binding by hemoglobin. PMID- 6243645 TI - Phosphatidic acid accumulation in the membranes of Escherichia coli mutants defective in CDP-diglyceride synthetase. AB - CTP-phosphatidic acid cytidylyltransferase (CDP-diglyceride synthetase) is a key enzyme in the biogenesis of membrane phospholipids in Escherichia coli. Using a modification of a previously described autoradiographic screening procedure (Raetz, C. R. H. (1975) Proc. Natl. Acad. Sci. U.S.A. 72, 2274-2278), we have isolated six mutant strains in which the specific activity of the synthetase is 1 to 10% that of the wild type, as judged by in vitro assays. The synthesis of dCDP diglyceride, as well as CDP-diglyceride, is defective in these organisms. The mutations responsible for the enzyme defects (designated cds) all map in the same location near minute 4 on the chromosome. Although none of the mutants obtained are temperature-sensitive for growth, all of them exhibit significantly elevated levels of phosphatidic acid in vivo. The highest increase is observed in the mutant GL60, in which phosphatidic acid constitutes about 5% of the membrane lipid, in contrast to 0.2% in typical wild type strains. The accumulation of phosphatidic acid occurs primarily at the expense of phosphatidylglycerol and cardiolipin, but the total lipid-to-protein ratio of GL60 is nearly normal. In vivo labeling of GL60 with 32Pi suggests that the increased phosphatidic acid pool is the result of a partial metabolic block early in the phospholipid pathway, but that most of this expanded pool is nonetheless available for de novo synthesis. PMID- 6243646 TI - Electrostatic interactions in cytochrome c. The role of interactions between residues 13 and 90 and residues 79 and 47 in stabilizing the heme crevice structure. PMID- 6243647 TI - Protein effects on the activity of guanosine 3':5'-monophosphate-dependent protein kinase. PMID- 6243648 TI - Loss of choleragen receptors and ganglioside upon differentiation of 3T3-L1 preadipocytes. AB - 3T3-L1 preadipocytes differentiate in culture into cells having the enzymatic and morphological characteristics of adipocytes. Differentiation is accompanied by a decrease in total cellular ganglioside content; the ganglioside level is 1.8 to 2.5-fold higher in undifferentiated than in differentiated cells. Gangliosides GM3 and GD1a constitute a majority of total cell gangliosides in both cell types, while ganglioside GM1, the putative choleragen receptor, constitutes less than 5%. Differentiation results in a 75 to 85% decrease in ganglioside GM1. An inverse correlation exists between the percentage of adipocytes in the cell population and: 1) total ganglioside and ganglioside GM1 content, and 2) surface ganglioside GM1 as estimated by choleragen binding or fluorescent staining of bound choleragen. Nondifferentiating 3T3-C2 control cells do not exhibit changes in total ganglioside, ganglioside GM1, or choleragen binding that are observed with 3T3-L1 cells. PMID- 6243649 TI - Increased fluidity and loss of temperature and Ca2+/Mg2+ sensitivity in nuclear membranes upon removal from the membrane-associated nuclear matrix proteins. PMID- 6243650 TI - Binding of cholecystokinin to high affinity receptors on isolated rat pancreatic acini. AB - The binding of cholecystokinin (CCK) to its receptors on isolated rat pancreatic acini was investigated employing high specific activity, radioiodinated CCK (125I BH-CCK), prepared by the conjugation of 125I-Bolton-Hunter reagent (125I-BH) to CCK. Binding was specific, time-dependent, reversible, and linearly related to the acinar protein concentration. After incubation for 30 min at 37 degrees C, the 125I-BH-CCK both in the incubation medium and bound to acini remained intact, as judged by gel filtration and trichloroacetic acid precipitation studies. Scatchard analysis was compatible with two classes of binding sites on acini: a very high affinity site (Kd, 64 pM) and a lower affinity site (Kd, 21 nM). 125I BH-CCK binding to acini was competitively inhibited by CCK and four of its analogues in proportion to their biological potencies but not by unrelated hormones. Stimulation of amylase secretion by CCK and inhibition of 125I-BH-CCK binding by the same analogues carried out under identical conditions revealed a correlation (r = 0.99) between binding potency and amylase secretion. Stimulation of amylase secretion by CCK closely paralleled the occupancy of the high affinity CCK binding sites. It is concluded that the high affinity CCK binding sites most likely are the receptors mediating the stimulation of amylase secretion by CCK. PMID- 6243651 TI - Loss of beta-adrenergic receptor-guanine nucleotide regulatory protein interactions accompanies decline in catecholamine responsiveness of adenylate cyclase in maturing rat erythrocytes. PMID- 6243652 TI - Correlation between membrane potential changes and superoxide production in human granulocytes stimulated by phorbol myristate acetate. Evidence for defective activation in chronic granulomatous disease. PMID- 6243653 TI - Regulation of liver phosphorylase phosphatase by glutathione disulfide. AB - The mechanism of inactivation of rabbit liver phosphorylase phosphatase by glutathione disulfide (GSSG) was investigated. The catalytic subunit of phosphorylase phosphatase was inactivated by GSSG and other disulfides. Inactivation by GSSG was a concentration-dependent process and resulted in the formation of an inactive, stable enzyme species. The inactivated enzyme could be reactivated by addition of various sulfhydryl compounds, including glutathione (GSH). Homogeneous phosphorylase phosphatase contains, per mol of catalytic subunit (Mr = 33,000), two sulfhydryl groups, one of which reacted with GSSG to form inactive enzyme. Binding studies with [glycine-2-3H]GSSG revealed simultaneous incorporation of 3H radioactivity into the catalytic subunit and stoichiometric loss of catalytic activity. Treatment of the 3H-labeled enzyme with GSH was accompanied by release of 3H radioactivity from the enzyme and restoration of enzyme activity. The results suggest that inactivation of phosphorylase phosphatase by GSSG results from the formation of a mixed disulfide between GSSG and one of the two sulfhydryl groups in the catalytic subunit. PMID- 6243654 TI - D-Mannitol oxidation in the land snail, Helix aspersa. AB - Respiration by mitochondrial preparations from hepatopancreas tissue of the land snail Helix aspersa is stimulated by D-mannitol. The rate of mannitol-stimulated respiration is approximately one-half that given by succinate, the most effective substrate thus far tested with these preparations. Mannitol-stimulated respiration is cyanide-insensitive but is not inhibited by salicylhydroxamate. The product of the membrane-bound mannitol-oxidizing activity was shown to be D mannose by thin layer chromatography, high voltage electrophoresis of the germanate and borate complexes, gas chromatography of the trimethylsilyl derivative, low resolution mass spectrometry of the trimethylsilyl derivative, and by an enzymatic method dependent upon phosphomannose isomerase. The reaction mannitol + O2 leads to mannose is stoichiometric; however, it is not known whether O2 is the immediate electron acceptor. The activity in Helix mitochondria is thus unique among most alditol-oxidizing enzymes in not being pyridine nucleotide linked and in acting on carbon 1 rather than carbon 2. PMID- 6243655 TI - Transient state kinetic studies of Ca2+-dependent ATPase and calcium transport by cardiac sarcoplasmic reticulum. Effect of cyclic AMP-dependent protein kinase catalyzed phosphorylation of phospholamban. PMID- 6243656 TI - Transcription of adenoviral genetic information in isolated nuclei. Characterization of viral RNA sequences synthesized in vitro. AB - The virus-specific RNA sequences synthesized in nuclei isolated from adenovirus type 2-infected HeLa cells comprise a fraction of the total RNA similar to that observed with RNA made in vivo. By 16 h after infection, for example, some 25% of the RNA made in isolated nuclei is transcribed from adenoviral DNA. Only 10 to 15% of the adenoviral RNA sequences synthesized in nuclei isolated during the late phase of infection are transcribed by form III RNA polymerase. This RNA, whose synthesis is resistant to 0.5 microgram/ml, but sensitive to 200 microgram/ml of alpha-amanitin, sediments at about 5 S in denaturing sucrose gradients and must, therefore, represent the virus-associated RNAs. The remainder of the sequences are transcribed by form II RNA polymerase and sediment as several RNA species in denaturing sucrose gradients. The largest of these exhibits the size, 55 to 60 S, expected of a complete transcript of the major, adenoviral transcriptional unit expressed during the late phase. Hybridization of RNA 32P-labeled in nuclei isolated during the late phase of infection to restriction endonuclease fragments of adenoviral DNA immobilized on nitrocellulose filters suggests that sequences of this transcriptional unit are indeed transcribed in vitro. To make a detailed assessment of the fidelity of transcription in isolated nuclei, transcription reactions were performed in the presence of 5-mercuricytidine 5'-triphosphate and the RNA mercurated in vitro separated from endogenous RNA by chromatography on sulfhydryl-agarose columns by a stringent procedure. After demercuration, RNA made in nuclei isolated 20 h following adenovirus type 2 infection was hybridized to the separated strands of restriction endonuclease fragments of 32P-labeled adenovirus type 2 DNA. Such RNA is complementary to the r strand of adenoviral DNA from 16.6 units to a point to the right of 98.3 units. These sequences comprise the major transcriptional unit expressed during the late phase (Fig. 1). It is therefore clear that the fidelity of transcription of adenoviral DNA by form II RNA polymerase is preserved in isolated nuclei. Two 1-strand transcriptional units, those of the IVa2 and ts36 genes (see Fig. 1) are also active at 20 h after infection. The results of similar analysis of RNA made in nuclei isolated 4 and 12 h after infection are also presented and discussed in terms of the mapping of individual transcriptional units within the type 2 adenoviral genome and the temporal regulation of adenoviral gene expression during productive infection. PMID- 6243657 TI - Effect of triiodothyronine on the synthesis and degradation of the small subunit of renal cortical (Na+ + K+)-adenosine triphosphatase. PMID- 6243658 TI - Characterization of a cyclic AMP-binding protein from bakers' yeast. Identification as a regulatory subunit of cyclic AMP-dependent protein kinase. PMID- 6243659 TI - The purification and properties of chicken liver RNase: An enzyme which is useful in distinguishing between cytidylic and uridylic acid residues. AB - A heat-stable endoribonuclease isolated from chicken liver has been purified to homogeneity as evidenced by the presence of a single protein band upon polyacrylamide gel electrophoresis. The enzyme can, in limit digests of 5 S rRNA and 5.8 S rRNA, dinstinguish between cytidylic and uridylic acids bonds at a ratio of 61:1 and, therefore, may be useful in RNA sequence analysis. The means by which the enzyme hydrolyzes substrate is unusual in that kinetic data do not support a simple formation and breakdown of an enzyme . substrate complex. Rather, the existence of a second complex, consisting of 2 mol of substrate and one of enzyme, derived from the initial enzyme . substrate complex, is postulated. In common with the other endonucleases, enzyme activity is inhibited by free poly(A) or tracts of the polypurine present at the 3'-terminus of RNA. Reversal of inhibition and restoration of activity may be achieved by the addition of low concentrations of spermidine to reaction mixtures. PMID- 6243660 TI - RNA priming of DNA replication by bacteriophage T4 proteins. AB - Bacteriophage T4 DNA replication proteins have been shown previously to require ribonucleoside triphosphates to initiator new DNA chains on unprimed single stranded DNA templates in vitro. This DNA synthesis requires a protein controlled by T4 gene 61, as well as the T4 gene 41, 43 (DNA polymerase), 44, 45, and 62 proteins, and is stimulated by the gene 32 (helix-destabilizing) protein. In this paper, the nature of the RNA primers involved in DNA synthesis by the T4 proteins has been determined, using phi X174 and f1 DNA as model templates. The T4 41 and "61" proteins synthesize pentanucleotides with the sequence pppA-C(N)3 where N in positions 3 and 4 can be G, U, C, or A. The same group of sequences is found in the RNA at the 5' terminus of the phi X174 DNA product made by the seven T4 proteins. The DNA product chains begin at multiple discrete positions on the phi X174 DNA template. The characteristics of the T4 41 and "61" protein priming reaction are thus appropriate for a reaction required to initiate the synthesis of discontinuous "Okazaki" pieces on the lagging strand during the replication of duplex DNA. PMID- 6243661 TI - Interaction between DNA gyrase and its cleavage site on DNA. PMID- 6243662 TI - Endocrine effects of naloxone-induced opiate receptor blockade. PMID- 6243664 TI - Glucocorticoid and partial mineralocorticoid deficiency associated with achalasia. AB - A number of patients with ACTH unresponsiveness resulting in glucocorticoid deficiency with normal mineralocorticoid activity have been described. This could be due to an inherited defect within the adrenal gland causing primary unresponsiveness to ACTH or to an inherited progressive degenerative process. The association of achalasia, lack of lacrimation, and glucocorticoid deficiency in two pairs of siblings with normal mineralocorticoid activity has been recently reported. Our case describes an 8.8-yr-old female with glucocorticoid insufficiency, partial mineralocorticoid deficiency, achalasia, and evidence of decreased lacrimation. Sodium depletion produced hyponatremia, and she was unable to increase her plasma aldosterone levels sufficiently, although PRA was markedly elevated. Our case may be part of a progressive degenerative process, possibly affecting both the autonomic nerve structures and the adrenal gland, leading not only to glucocorticoid deficiency but also to abnormal mineralocorticoid secretion. PMID- 6243663 TI - New studies of the 11 beta-hydroxylase and 18-hydroxylase enzymes in the hypertensive form of congenital adrenal hyperplasia. AB - Studies in four children with congenital adrenal hyperplasia due to 11 beta hydroxylase deficiency provide evidence for two separate 11 beta-hydroxylating systems in the adrenal zona fasciculata and zona glomerulosa. In addition, these studies support the proposal that the adrenal 11 beta- and 18-hydroxylating activities are related and may involve the same enzyme protein and catalytic site. In the untreated or poorly treated state, despite elevation of deoxycorticosterone (DOC) and tetrahydrodeoxycorticosterone, urinary free 18 hydroxy-DOC was in the low normal range and did not increase normally with ACTH. PRA and urinary free 18-hydroxycorticosterone (18-OHB), tetrahydroaldosterone (TH Aldo), and pH 1 aldosterone were suppressed in the untreated and ACTH periods. Glucocorticoid administration suppressed plasma ACTH, and urinary tetrahydro-DOC and free DOC excretion decreased to the normal range. Concomitantly, there was a rise in PRA accompanied by parallel increase in urinary 18-OHB, urinary TH Aldo, and pH 1 aldosterone. While on dexamethasone, a low sodium diet (10 meq/day) resulted in prompt sodium retention, with a further rise in PRA and urinary 18 OHB, TH Aldo, and pH 1 aldosterone. These studies indicate the presence of both an 11 beta- and an 18-hydroxylase deficiency in the zona fasciculata and normal 11 beta- and 18-hydroxylase function in the zona glomerulosa, suggesting that these two enzymatic functions are related and that separate enzyme systems are present in the two zones. PMID- 6243665 TI - Interaction of crude and pure chorionic gonadotropin with the thyrotropin receptor. PMID- 6243666 TI - Common clinical indices of thyroid hormone action: relationships to serum free 3,5,3'-triiodothyronine concentration and estimated nuclear occupancy. PMID- 6243667 TI - Effects of physiological infusion of epinephrine in normal humans: relationship between the metabolic response and beta-adrenergic binding. AB - In normal humans, infusion of epinephrine for 4 h increased plasma epinephrine to 411 +/- 38 pg/ml but had no significant effect on palsma insulin or glucagon levels. Epinephrine produced a prompt 45% rise in glucose output (P less than 0.01) and a 120% rise in FFA (P less than 0.001), both of which declined to basal levels by 60-90 min. Glucose clearance decreased by 25% (P less than 0.005) and remained suppressed for 4 h. The binding of [125I]hydroxybenzylpindolol to lymphocytes was unchanged after epinephrine infusion. We conclude that in normal humans 1) physiological increments in epinephrine have a persistent effect in decreasing glucose clearance but only transiently increase hepatic glucose output and FFA levels and 2) this refractoriness of liver and adipose tissue to epinephrine occurs without a concomitant decrease in beta-adrenergic binding to lymphocytes. PMID- 6243668 TI - Adrenocorticotropin release by tryptophan in man. AB - Previous work from this laboratory indicated significant elevations of cortisol after the administration of tryptophan. The current investigation was designed to confirm this observation and study the effect of this agent on ACTH. Cortisol rose 12.4 +/- 5.2 microgram/dl (mean +/- SD) in 10 of 12 tests (P less than 0.02). Responding patients had rises of ACTH averaging 101.8 +/- 45.8% (range, 40 159 pg/ml) above baseline. The time course of the ACTH change closely paralleled that of cortisol, and there were significant correlations between the rises of the two substances (r = 0.81; P less than 0.01). The current data strongly suggest that tryptophan administration stimulates ACTH release, possibly through activation of the central serotonergic nervous system. Review of the literature suggests the possibility that ACTH stimulation only occurs at high plasma tryptophan (and presumably brain serotonin) concentrations, with ACTH inhibition occuring at lower levels. PMID- 6243669 TI - The role of the beta-adrenergic mechanism in the hypergastrinemia of hyperthyroidism. PMID- 6243670 TI - [3H]Spiperone binding to human anterior pituitaries and pituitary adenomas secreting prolactin, growth hormone, and adrenocorticotropic hormone. PMID- 6243671 TI - Mineralocorticoid unresponsiveness with severe neonatal hyponatremia and hyperkalemia. AB - An infant with severe neonatal hyponatremia and hyperkalemia is described. Although marked elevations of urinary 17-hydroxycorticosteroids suggested an 18 dehydrogenase aldosterone biosynthetic defect, the infant proved to have mineralocorticoid unresponsiveness, or pseudohypoaldosteronism. Dietary sodium supplementation and ion exchange resin administration resulted in normalization of serum electrolytes and urinary 17-hydroxycorticosteroids. ACTH infusion produced natriuresis, suggesting the need for additional sodium supplementation during the stress of illness, with a resultant increase in ACTH secretion. Determinations of the relative amounts of urinary 18-hydroxy and aldosterone metabolites appear necessary for early definitive diagnosis of the disorder. PMID- 6243672 TI - Enzyme-linked immunosorbent assays adapted for serotyping of human rotavirus strains. AB - Five enzyme-linked immunosorbent assay systems were adapted for serotyping human rotavirus strains and were compared with a sensitive complement fixation test in terms of specificity and sensitivity. The assays differed mainly with regard to the antibody systems involved in the double sandwich. Serotype differentiation of 34 rotavirus strains was achieved by determining a neutralization endpoint titer, either with a constant antiserum-varying antigen dilution method or vice versa. The procedure which proved to be highly specific and sensitive was one with two type-specific hyperimmune sera (enzyme-linked immunosorbent assay system 5) instead of only one, as in the four other systems. PMID- 6243673 TI - Variable susceptibility of mice to group B coxsackievirus infections. AB - Laboratory strains of group B coxsackievirus serotypes 1 to 6 were inoculated intraperitoneally into newborn mice of differing genetic backgrouns. Of the four genetic strains investigated, C3H mice appeared to be resistant to all six serotypes, whereas BALB/c mice were most susceptible. Swiss mice and a random bred Swiss strain (COH) were intermediate in susceptibility. The findings underscore the fact that clinical isolation attempts and experimental studies involving group B coxsackieviruses must take into account both the virus strain used and the genetic background of the host. For clinical isolation of these viruses, the BALB/c mouse may be the most suitable of th strains tested. PMID- 6243674 TI - Differentiation of cytomegalovirus antigens by their reactivity with various classes of human antibodies in the indirect fluorescent antibody test. AB - Human sera containing immunoglobulin G (IgG), IgA, and IgM antibodies were tested by immunofluorescence for reactivity with cytomegalovirus-infected cell cultures and with early antigens of cytomegalovirus produced by treating the infected cultures with either bromodeoxyuridine or cytosine arabinoside. IgG antibody but not IgM antibody reacted with early antigens produced in bromodeoxyuridine treated infected cultures. This observation on a small sample of sera suggested that a positive IgM reaction with an infected, nontreated culture and a negative reaction with a bromodeoxyuridine-treated infected culture may indicate a positive specific IgM reaction for cytomegalovirus, even in the presence of IgM rhematoid factor. The hyothesis requires further testing. The different classes of antibody did not all react or did not react to the same extent with early antigens produced in infected cells blocked with cytosine arabinoside or bromodeoxyuridine. This observation indicates that different antigens were being produced as a result of the two treatments. PMID- 6243675 TI - Adrenergic mechanisms for the effects of epinephrine on glucose production and clearance in man. AB - THE PRESENT STUDIES WERE UNDERTAKEN TO ASSESS THE ADRENERGIC MECHANISMS BY WHICH EPINEPHRINE STIMULATES GLUCOSE PRODUCTION AND SUPPRESSES GLUCOSE CLEARANCE IN MAN: epinephrine (50 ng/kg per min) was infused for 180 min alone and during either alpha (phentolamine) or beta (propranolol)-adrenergic blockade in normal subjects under conditions in which plasma insulin, glucagon, and glucose were maintained at comparable levels by infusion of somatostatin (100 mug/h), insulin (0.2 mU/kg per min), and variable amounts of glucose. In additional experiments, to control for the effects of the hyperglycemia caused by epinephrine, variable amounts of glucose without epinephrine were infused along with somatostatin and insulin to produce hyperglycemia comparable with that observed during infusion of epinephrine. This glucose infusion suppressed glucose production from basal rates of 1.8+/-0.1 to 0.0+/-0.1 mg/kg per min (P < 0.01), but did not alter glucose clearance. During infusion of epinephrine, glucose production increased transiently from a basal rate of 1.8+/-0.1 to a maximum of 3.0+/-0.2 mg/kg per min (P < 0.01) at min 30, and returned to near basal rates at min 180 (1.9+/-0.1 mg/kg per min). Glucose clearance decreased from a basal rate of 2.0+/-0.1 to 1.5+/-0.2 ml/kg per min at the end of the epinephrine infusion (P < 0.01). Infusion of phentolamine did not alter these effects of epinephrine on glucose production and clearance. In contrast, infusion of propranolol completely prevented the suppression of glucose clearance by epinephrine, and inhibited the stimulation of glucose production by epinephrine by 80+/-6% (P < 0.001). These results indicate that, under conditions in which plasma glucose, insulin, and glucagon are maintained constant, epinephrine stimulates glucose production and inhibits glucose clearance in man predominantly by beta adrenergic mechanisms. PMID- 6243676 TI - Estrogen dependence of a gonadotropin-induced steroidogenic lesion in rat testicular Leydig cells. AB - Leydig cells isolated from the testes of rats treated with intravenous exogenous gonadotropin (hCG) or subcutaneous gonadotropin-releasing hormone (GnRH) show markedly decreased luteinizing hormone (LH) receptors and a partial block in testicular 17,20 desmolase activity. In contrast, Leydig cells from animals with equivalent degrees of LH receptor loss induced by subcutaneous hCG treatment show no change in 17,20 desmolase activity. These findings indicated that the acuteness of gonadotrophic stimulation, rather than the extent of LH receptor loss, was responsible for the steroidogenic lesion. A role of estradiol in the enzymatic block produced in vivo by acute elevation of circulating gonadotropin (intravenous hCG or GnRH-stimulated endogenous LH) was suggested by rapid elevations of testicular 17beta-estradiol within 30 min after intravenous hCG, whereas more gradual increases in estradiol occurred 4-8 h after subcutaneous hCG. The inhibitory effect of endogenous estrogen on testicular steroidogenesis was confirmed by the ability of an estrogen antagonist (Tamoxifen) to prevent the reduction of testosterone responses caused by intravenous hCG and subcutaneous GnRH. In addition, Tamoxifen significantly increased the number of LH receptors in Leydig cells from both control and gonadotropin-desensitized animals. These findings indicate that the acute elevations of intratesticular estrogen produced by treatment with hCG or GnRH are responsible for the steroidogenic lesion seen in gonadotropin-desensitized Leydig cells. These results also suggest that locally produced estrogens contribute to the regulation of testicular LH receptors and 17,20 desmolase activity. PMID- 6243677 TI - Epinephrine-induced insulin resistance in man. AB - Endogenous release of epinephrine after stress as well as exogenous epinephrine infusion are known to result in impaired glucose tolerance. Previous studies of man and animals have demonstrated that this effect of epinephrine results from inhibition of insulin secretion and augmentation of hepatic glucose production. However, the effect of epinephrine on tissue sensitivity to insulin, and the relative contributions of peripheral vs. hepatic resistance to impaired insulin action, have not been defined. Nine young normal-weight subjects were studied with the insulin clamp technique. Plasma insulin was raised by approximately 100 muU/ml while plasma glucose concentration was maintained at basal levels by a variable glucose infusion. Under these conditions of euglycemia, the amount of glucose metabolized equals the glucose infusion rate and is a measure of tissue sensitivity to insulin. Subjects received four studies: (a) insulin (42.6 mU/m(2).min), (b) insulin plus epinephrine (0.05 mug/kg.min), (c) insulin plus epinephrine plus propranolol (1.43 mug/kg.min), and (d) insulin plus propranolol. During insulin administration alone, glucose metabolism averaged 5.49+/-0.58 mg/kg.min. When epinephrine was infused with insulin, glucose metabolism fell by 41% to 3.26 mg/kg.min (P < 0.001). After insulin alone, hepatic glucose production declined by 92% to 0.16+/-0.08 mg/kg.min. Addition of epinephrine was associated with a delayed and incomplete suppression of glucose production (P < 0.01) despite plasma insulin levels >100 muU/ml. When propranolol was administered with epinephrine, total glucose metabolism was restored to control values and hepatic glucose production suppressed normally. Propranolol alone had no effect on insulin-mediated glucose metabolism. These results indicate that epinephrine, acting primarily through a beta-adrenergic receptor, markedly impairs tissue sensitivity to an increase in plasma insulin levels, and that this effect results from both peripheral and hepatic resistance to the action of insulin. PMID- 6243678 TI - Cerebral atrophy following ACTH therapy. AB - In a study of 15 patients with infantile spasms and Lennox syndrome 4 (26.7%) showed no cerebral atrophy and 11 (73.3%) showed mild ventricular and sulcal enlargement before ACTH therapy. Ventricular and sulcal enlargement increased soon after ACTH therapy in most patients. Cerebral atrophy was reversible at over 1 month after ACTH therapy. However, in three instances, cerebral atrophy was not reversible, and one patient with infantile spasms had chronic subdural effusion, which appeared to be a complication of treatment with ACTH. Patients on ACTH therapy should be carefully monitored. PMID- 6243679 TI - Computed tomography in primary hepatocellular carcinoma. AB - Abdominal computed tomography was performed on seven patients with primary hepatocellular carcinoma. The liver appeared normal in one patient, while in the other six patients the tumor was identified as an area of decreased attenuation. In four cases, the tumor was seen better following intravenous administration of a contrast agent, and, in two of these cases, it was not seen on the precontrast scans. In only one case was the hepatoma better seen on the precontrast examination, and it could still be identified following contrast enhancement. Hepatomegaly and an irregular hepatic contour were other findings in these patients. PMID- 6243680 TI - Immunocytochemical characterization of ACTH-like immunoreactivity in cerebral nerves and in endocrine cells of the pituitary and gastrointestinal tract by using region-specific antisera. AB - The development and use of region-specific antisera for characterizing pituitary and extrapituitary ACTH immunoreactivity are described. The pituitary corticotrophs and melanotrophs, as well as a system of cerebral nerves, contain antigenic determinants, indistinguishable from those of true, pituitary ACTH [1 39]. The distributional patterns of cerebral nerves, most probably containing ACTH [1-39], is of interest in view of documented behavioral effects of ACTH fragments, as well as the possible interaction between ACTH and certain opioid peptides. Studies on antropyloric gastrin cells, previously reported to contain immunoreactive ACTH-like material indicate that the main form of immunoreactive peptide stored in these cells contains only part of the ACTH [1-39] sequence. Its relation to fragments of the ACTH molecule, as well as to yet unknown (hormonal) peptides, is discussed. PMID- 6243681 TI - 5'-Nucleotidase activities in cultured rat liver epithelial and fibroblast cells. AB - Cell cultures of adult rat liver produced two distinct morphologic cell types: epithelial cells polygonal in shape and growing in nests of closely apposed cells, and fibroblast cells stellate in shape with little cell-cell contact at low density growth, but aligning in parallel arrays at high density. These two morphologic variants displayed dramatic differences in histochemically demonstrable 5'-nucleotidase activities. Fibroblast cells exhibited great activity throughout the cytoplasm with no concentration of activity in the cell membrane. The lesser activity in epithelial cells was concentrated on the cell membrane. The importance of this finding to the interpretation of data derived from experiments with whole liver homogenates is discussed. PMID- 6243682 TI - Use of osmium-ferrocyanide treatment for improved lysosomal acid trimetaphosphatase reaction and subcellular detail in thyroid follicular cells. AB - The histochemical reaction for acid trimetaphosphatase in addition to secondary tissue treatment with an osmium-ferrocyanide mixture was used to study lysosomes and phagolysosomes in the mouse thyroid gland. The osmium-ferrocyanide postfixation enhanced reaction product localization, reduced diffuse reaction, and improved membrane contrast. In addition, the ultrathin tissue sections did not require heavy metal staining, thus eliminating potential stain artifacts due to precipitation. In view of the improved tissue preservation and enzyme localization, it is suggested that osmium-ferrocyanide postfixation be used after the acid trimetaphosphatase method. PMID- 6243683 TI - Immunohistochemical localization of cyclic GMP in goldfish retina. AB - The immunocytochemical procedure for cyclic GMP (cGMP) localization has been modified by the development of: 1) an anti-cGMP antibody depleted control serum and 2) a tissue preadsorption procedure that greatly reduces nonspecific fluorescence. cGMP remaining associated with tissue sections following prolonged exposure to aqueous buffer was determined, by extraction and measurement by radioimmunoassay, to be approximately 38% of the initial cGMP content. Application of this improved immunohistochemical procedure to goldfish retinas reveals the highest concentrations of cGMP to be associated with the cone inner segments and nuclei of the photoreceptors. This retinal distribution of cGMP is in good agreement with that independently determined by microdissection studies. The validity of this procedure is therefore strengthened and cautions to its application and interpretation are outlined. PMID- 6243684 TI - An improved method for the collection of serial cells for electron microscopic analysis of their immunocytochemical stain. AB - A technique to find serial views of cells stained for more than one hormone is described. As the number of stains employed is increased, there is less probability that matching views for all stains will be found. We have found a set of 6 series (including 2 sections per grid and 3 alternating stains) to be optimal for recognition of morphology and collection of a significant number of cells. PMID- 6243685 TI - Histochemical evaluation of lymphocytes in hypogammaglobulinemia. Decreased number of 5'-nucleotidase-positive cells. AB - With the use of a histochemical technique, 5'-nucleotidase activity was examined in peripheral blood lymphocytes from patients with primary hypogammaglobulinemia. Our current study demonstrates that the decrease in 5'-nucleotidase activity in congenital agammaglobulinemia, previously demonstrated by a radiochemical assay, is associated with a reduction in the number of cells containing 5'-nucleotidase rather than with a decrease of the enzyme activity per cell. Both sheep erythrocyte rosette-forming and nonrosette-forming PBMs have reduced percentages of 5'-nucleotidase-containing cells in subjects with the enzyme deficiency. The reduced percentage of 5'-nucleotidase-containing mononuclear cells in patients with congenital agammaglobulinemia was evident in both monocyte-contaminated and monocyte-depleted cell preparations. PMID- 6243686 TI - Inhibition of platelet function by antithrombotic agents which selectively inhibit low-Km cyclic 3',5'-adenosine monophosphate phosphodiesterase. PMID- 6243687 TI - Dibutyryl cyclic AMP does not influence glomerular collagen or basement membrane production in vitro. AB - Glomeruli isolated from normal rat renal cortex were incubated for 3 hr with radiolabeled proline in the presence or absence of dibutyryl cyclic AMP. Following incubation, glomerular basement membranes were purified with osmotic lysis followed by selective solubilization of the cell membranes and intracellular proteins with detergents. This technique permitted quantitative recovery of radiolabeled membranes synthesized under different incubational conditions. Dibutyryl cyclic AMP did not affect the incorporation of radioactive precursor glomerular basement membrane (control = 14.72 +/- 1.08 cpm/microgram of membrane protein; cyclic AMP = 14.43 +/- 1.13). Nondialyzable [14C]protein and hydroxy[14C]proline were also measured in the media and in the various glomerular cell fractions obtained during isolation of the basement membranes. Protein ([14C]proline) and collagen (OH[14C]proline) secretion into the media in incubations with cyclic AMP did not differ from that in control incubations. OH[14C]proline content was greatest (congruent to 23% in the water-soluble fraction recovered after osmotic lysis, but significant amounts of OH[14C]proline were also associated with the detergent-solubilized cell fractions. Dibutyryl cyclic AMP had no effect on either glomerular protein or collagen synthesis in these experiments. The results suggest that total glomerular basement membrane production in mixed cell populations is not modulated via a cyclic AMP- coordinated mechanism but do not exclude the possibility that cyclic AMP modulates the amount or kind of collagen synthesis by individual glomerular cell types. PMID- 6243688 TI - Effect of aging and cellularity on lipolysis in isolated mouse fat cells. AB - The effects of age and cellularity on lipolysis have been investigated in isolated epididymal fat cells from both Swiss albino mice and Sprague-Dawley rats. No significant lipolytic response to glucagon could be demonstrated with adipocytes from either young or old mice, while glycerol output was increased by this hormone with fat cells from young rats. Larger adipocytes from older mice showed significantly greater isoproterenol-stimulated lipolysis than those from younger animals if the glycerol output was expressed on a per cell basis. However, the lipolytic response per cell appeared to be equivalent in young and old rat adipocytes with either isoproterenol or ACTH-(1-24). In a complete aging study, relationships between body weight, epididymal fat pad weight and cellularity were examined covering the life span of the mouse. ACTH-(1-24)- and dibutyryl cyclic AMP-stimulated lipolysis increased with age and cell size but fell at senescence when adipocyte size diminished. Although an effect of aging per se cannot be ruled out with the experimental techniques used in the present study, a dominant influence of adipocyte size on the lipolytic process was demonstrated. PMID- 6243689 TI - Cardiac rehabilitation in a family practice setting. AB - In January 1978, a cardiac rehabilitation program was begun at Fort Ord, California. The program is unique in being designed and run by family physicians. In the Medical Intensive Care Unit, the patient with a myocardial infarction is started on a graduated exercise program and a structured course concerning heart disease. Eight weeks after the infarction, the patient is asked to join an out patient exercise class meeting three times a week. The patient's progress is followed by serial treadmill and blood tests. After training for six months, the patients have shown an increase in exercise tolerance and a decrease in incidence of readmission for cardiac disease. Most importantly, the patients have become actively involved in their own treatment. PMID- 6243690 TI - [Apudomas in OrL Apropos of 6 cases (with 1 chemodectoma and 1 carcinoid tumor of the larynx); criticism of the apudoma concept]. PMID- 6243691 TI - Innervation, synaptic physiology, and ultrastructure of three muscles of the second maxilla in crayfish. PMID- 6243692 TI - Multiple innervation of Purkinje cells by climbing fibers in the cerebellum of the adult staggerer mutant mouse. AB - Intracellular recordings from Purkinje cells (PC) in the cerebellum of adult staggerer mutant mice revealed that the orthodromic response of PCs to juxtafastigial (JF) stimulation closely resembled a climbing fiber response (CFR). However, for most of the PCs studied, these responses were graded in a stepwise manner when the stimulus strength was increased. The underlying excitatory synaptic potentials (EPSPs) had the typical shape of EPSPs mediated through climbing fibers (CFs), but their size fluctuated in discrete steps, the highest one reaching the firing level. In the same PCs, the size of the spontaneous EPSPs fluctuated in a similar fashion and the frequency of each step was in the range of CF-mediated EPSPs. These results strongly suggest that in staggerer mice several CFs synapse with each PC instead of a single CF as in normal adults. Furthermore, the activation through some of these CFs does not reach the firing level of the corresponding PC. PMID- 6243693 TI - Changes in glycoprotein metabolism in the cerebral cortex following first exposure of dark-reared rats to light. PMID- 6243694 TI - Differential regulation by guanine nucleotides or opiate agonist and antagonist receptor interactions. PMID- 6243695 TI - Effect of organophosphorus insecticides on the oxidative processes in rat brain synaptosomes. PMID- 6243696 TI - Relationship between the actions of calcium ions, opiods, and prostaglandin E1 on the level of cyclic AMP in neuroblastoma x glioma hybrid cells. PMID- 6243697 TI - Neurochemical characteristics of myelin-like structure in the chick retina. PMID- 6243698 TI - 2',3'-Cyclic nucleotide 3'-phosphohydrolase and lipids of myelin from multiple sclerosis and normal brains. PMID- 6243699 TI - Chronic hypoxia in rats: alterations of striato-nigral angiotensin converting enzyme, GABA, and glutamic acid decarboxylase. PMID- 6243700 TI - Effects of neomycin on calcium and polyphosphoinositide metabolism of guinea pig synaptosomes. PMID- 6243701 TI - Peripheral sympathetic function in patients with a polyneuropathy. AB - Abnormal peripheral vasoconstrictor responses to inspiration were found in the finger tips of 11 out of 20 patients with a suspected polyneuropathy, most of whom had no clinical evidence of autonomic involvement. Among these 11 patients the neuropathy involved both motor and sensory fibers in 9, sensory fibers alone in 1, and autonomic fibers alone in another; it was accompanied by electrical changes suggestive of axonal degeneration in 9 patients, and by normal findings in 1, while the remaining patient was not investigated electrophysiologically. In addition to conventional electrophysiological tests of somatic motor and sensory function, it is suggested that peripheral vasomotor function be evaluated when patients with a polyneuropathy are being investigated, in order to identify the spectrum of nerve fibers that are involved and thereby characterize the disorder more fully. PMID- 6243702 TI - The effect of dietary protein on the biological activity of cholecalciferol and its metabolites in the rachitic rat. AB - Rats maintained on low-protein rachitogenic diets show increased intestinal calcium transport, serum inorganic phosphate and increased endochondral calcification responses to calciferol, 25-hydroxycholecalciferol (25-OH-CC) and 1,25-dihydroxycholecalciferol (1,25-(OH)2CC). Because enhanced responses are observed with 1,25-dihydroxycholecalciferol as well as its precursors, it is unlikely that the effect of dietary protein is mediated by a change in the calciferol-25-hydroxylase and the 25-hydroxycholecalciferol-1 alpha-hydroxylase. Instead, it appears that either metabolism of 1,25-dihydroxycholecalciferol or its activity in the target organs is affected. PMID- 6243703 TI - The response of cyclic nucleotide content in liver and brown fat of rats weaned to different diets. AB - Rats were weaned on the 18th or 30th postnatal day to a high-fat, high carbohydrate or atherogenic diet. Twenty-four hours later, hepatic levels of cyclic guanosine 3',5'-monophosphate (cyclic GMP) and adenosine, 3',5'-cyclic monophosphate (cyclic AMP) were found to be higher in male animals aged 31 days fed the high-fat than those fed the high-carbohydrate diet. Prematurely weaned rats (day 18) reacted in the same way. However, feeding either diet resulted in higher hepatic cyclic nucleotide levels than found in rats kept with the dam. The atherogenic diet was least effective in raising these levels. After a 24-hour fast, cyclic nucleotide levels in liver and brown fat were elevated and hepatic levels could not be lowered by 6 hours of feeding the high-fat or atherogenic diet. In male 40-day-old rats, however, feeding for 2 hours was sufficient to lower these levels, more so with a high-carbohydrate than a high-fat diet. Since blood levels of glucagon are high, and those of insulin are low in 18-day-old rats that are not weaned and since their hepatic cyclic nucleotide levels are low, it is suggested that other factors, in addition to blood hormone levels, play a role in regulating cyclic nucleotide levels. PMID- 6243704 TI - Alcoholic thrombocytopenia: a brief review. PMID- 6243705 TI - The use of seclusion rooms and physical restraints in the treatment of psychiatric patients. PMID- 6243706 TI - Self-disclosure: a variable in the nurse-client relationship. PMID- 6243707 TI - Working with a dependent client in therapy: a clinical paper. PMID- 6243708 TI - Primary mental health care: an innovative model. PMID- 6243710 TI - Concept of wellness. PMID- 6243709 TI - A working concept of intellectualization. PMID- 6243711 TI - Calcium pyrophosphate dihydrate crystal deposition. PMID- 6243712 TI - Urachal carcinoma: diagnosis by computerized axial tomography. AB - A case of mucin-producing adenocarcinoma of the urachus is reported. Preoperative diagnosis was established by computerized axial tomography. The embryology, histogenesis, signs, symptoms, diagnostic criteria and treatment are discussed. PMID- 6243713 TI - Indicator bacteria and Salmonella in food-processing and domestic effluent. PMID- 6243714 TI - Topical ether and herpes simplex labialis. AB - In a double-blind, placebo-controlled study, 51 patients with recurrent herpes simplex labialis were treated with topical ether or placebo within 24 hours of onset of a lesion. There was no noteworthy difference between groups given ether and placebo in progression of lesions, healing time, duration or intensity of pain, and duration or quantity of virus excretion. The ether also failed to reduce appreciably lesion virus titer, even when lesions were cultured immediately after topical application. Despite these results, 75% of the patients receiving ether and 77% of those receiving placebo reported effective reduction of the severity and duration of lesions. The marked placebo effect in the treatment of recurrent herpes infection helps to emphasize the need for objective measurements and placebo-controlled studies. PMID- 6243715 TI - Association of herpes simplex thymidine kinase gene with chromosome No. 18 in transformed human cells. AB - The herpes simplex virus type-2 (HSV-2)-transformed human cell line HB-2-3 was fused with thymidine kinase (TK)-deficient mouse cells [LM(TK-)], and 12 independent hybrids were isolated with the use of the HAT (hypoxanthine, amethopterin, and thymidine)-ouabain selection system. Discontinuous polyacrylamide gel electrophoresis studies demonstrated that the HSV-2-specific TK was the selected enzyme in the hybrids. Isoenzyme analysis and karyotyping were used in the analysis of the hybrids for the presence of human chromosomes. All 12 hybrids contained human chromosome No. 18 and the enzyme peptidase A, which is encoded by a gene on this chromosome. Hybrids were exposed to bromodeoxyuridine (BrdUrd) as a means of selection for cells that had lost HSV-2 TK activity. Isoenzyme and karyotyping data obtained from 33 BrdUrd-resistant sublines were consistent with the hypothesis that the HSV-2 TK gene is associated with chromosome No. 18 in the HB-2-3 cell line. PMID- 6243716 TI - Inhibition of chemically induced carcinogenesis of canine cells in vitro by infection with mouse xenotropic type C virus. AB - C57L mouse xenotropic type C virus infection inhibited N-methyl-N'-nitro-N nitrosoguanidine (MNNG)-induced in vitro transformation of embryo cells from inbred beagles. Treatment with MNNG induced in vitro neoplastic transformation in uninfected canine cells but not in C57L virus-infected canine cells; the C57L virus-infected canine cells not treated with MNNG also remained untransformed. In this dog cell system, preinfection with a C57L mouse xenotropic type C virus inhibited in vitro neoplastic transformation induced by MNNG. PMID- 6243717 TI - Further studies on inhibition of Epstein-Barr virus release by bovine serum: partial purification and characterization of the inhibitor. AB - The antivirus release factor (AVRF) was extracted from adult bovine serum and was partially purified in three steps by 1) ammonium sulfate precipitation, 2) Sephadex G-200 chromatography, and 3) DEAE-Sephadex chromatography, procedures that together increased specific activity 160 times. In molecular sieve chromatography, AVRF was found in fractions close to IgM. The AVRF activity was sensitive to KIO4 (0.04 M) but not to trypsin (0.1%), UV irradiation, ethyl ether, and heating at 56 degrees C for 30 minutes. The AVRF neither neutralized infectivity of Epstein-Barr virus (EBV) from the P3HR-1 cell line nor inhibited intracellular virus yields at concentrations that inhibited release of virus into culture fluid. Cellular release of two other strains of EBV (QIMR-WIL and B95-8) was also inhibited by AVRF. Electron microscopic examination of P3HR-1 cells cultured in the presence of AVRF revealed peculiar interacytoplasmic vacuoles containing many mature virus particles with tail-like structures. PMID- 6243718 TI - Prevention of paralysis and suppression of lymphoma in wild mice by passive immunization to congenitally transmitted murine leukemia virus. AB - Lake Casitas wild mice were passively immunized as newborns with antiserum to congenitally transmitted murine leukemia virus. Immunization with immunoglobulin having a high neutralizing titer to ecotropic virus and a low titer to amphotropic virus correlated with the complete prevention of paralysis and a slight (25%), but statistically insignificant, reduction in the incidence of lymphoma. Occurrence of other tumor types and total mortality rate were not affected by immunization. PMID- 6243719 TI - Human lymphocyte blastogenesis responses to mouse mammary tumor virus. PMID- 6243720 TI - Leukocyte migration inhibition among breast cancer patients in response to various oncogenic viruses. AB - The direct leukocyte migration inhibition (LMI) test was done with leukocytes from healthy women and from patients with primary operable breast cancer, benign breast disease, or head and neck cancer. Purified preparations of murine mammary tumor virus (MuMTV), Mason-Pfizer monkey virus (MPMV), and murine leukemia virus (MuLV) were used. For each virus, the lowest 10th percentile of the LMI responses of controls was used to discriminate positive from negative responses. Leukocytes from 46 of 94 (49%) breast cancer patients responded to MuMTV, which was significantly different from each of the other test groups: Positive reactions were observed in only 9 of 67 (13%) healthy persons, 2 of 32 (6%) patients with benign breast tumors, and 2 of 20 (10%) patients with head and neck cancer. Although leukocytes from 29% of the breast cancer patients responded to MPMV, this response did not significantly differ from that observed in healthy women (14%), in patients with benign disease (20%), or in patients with head and neck cancer (20%). The leukocytes from the breast cancer patients were not reactive to MuLV. LMI tests to both MuMTV and extracts of MCF-7 cultured breast cancer cells were done in 36 breast cancer patients and 40 healthy women simultaneously. Of the breast cancer patients, 75% responded to MuMTV and/or MCF-7 antigen as compared to 18% of the controls (P less than 0.005). These data suggest that leukocytes from breast cancer patients are presensitized to MuMTV and antigen(s) present in MCF-7 breast cancer cell line, but not to MPMV or MuLV. PMID- 6243721 TI - Characterization of lymphoma-derived cell lines: comparison of cell lines positive and negative for Epstein-Barr virus nuclear antigen. I. Physical, cytogenetic, and growth characteristics. AB - Sixteen lymphoid cell lines were derived from patients with undifferentiated lymphoma of Burkitt's or non-Burkitt's type. They were obtained directly from tumor biopsies, from serous effusions, or from bone marrow. In 10 of the cell lines, the Epstein-Barr virus (EBV) nuclear antigen (EBNA) was undetectable; the remaining 6 lines were EBNA-positive (EB-pos). Of the 16 lines, 15 were aneuploid, with detectable chromosome "14q+ markers (11 had +8;14 translocations). These 15 lines, which included the EBNA-negative (EB-neg) lines, were believed to be of tumor cell origin. The remaining line consisted predominantly of diploid cells derived from normal lymphocytes, but some cells of tumor origin were present. Four EB-pos cell lines derived from EB-neg tumors had an aneuploid karyotype consistent with an origin from tumor cells (including no.8;14 translocation in two), which suggested that either tumor cells were infected with EBV in vitro or a tiny fraction of EB-pos tumor cells (or potential tumor cells) present in vivo gave rise to the predominant cell of the line. EB neg B-cell lines and EB-pos cell lines established from undifferentiated lymphomas differed greatly. EB-neg lines had consistently smaller electronic mean cell volumes and narrow-angle light scatter than did EB-pos lines. This finding correlated with a lower nuclear:cytoplasmic ratio in EB-pos lines. EB-neg lines also had higher saturation cell densities than did EB-pos lines under standard culture conditions. The data indicate either that EBV influences the morphologic and physiologic characteristics of lymphoid cell lines or that EB-neg B-cell lines and EB-pos cell lines are derived ultimately from different lymphocyte subpopulations or that both may apply. PMID- 6243722 TI - Characterization of lymphoma-derived cell lines: comparison of cell lines positive and negative for Epstein-Barr virus nuclear antigen. II. Surface markers. AB - Fifteen of 16 lymphoma-derived cell lines and the Faji and P3HR1 cell lines were characterized with regard to certain surface markers, particularly immunoglobulins, complement receptors, Epstein-Barr virus (EBV) receptors, and Fc receptors. Ten lines positive for EBV nuclear antigen (EB-pos) were stained weakly or not at all by antihuman immunoglobulin fluorescein isothiocyanate conjugates, whereas EBV nuclear antigen negative (EB-neg) cell lines stained brightly. EB-pos lines frequently manifested Fc receptors, particularly for 7S antibody, whereas EB-neg lines did not. Receptors for the C3b component of complement and for EBV, which correlated significantly with each other, were expressed to a much lesser extent by EB-neg lines than by EB-pos lines. These findings are pertinent to an understanding of the infrequent association of this virus with American undifferentiated lymphomas of the Burkitt's and non-Burkitt's types. PMID- 6243723 TI - Differential expression of two distinct endogenous retrovisus genomes in developing tissues of the domestic cat. PMID- 6243724 TI - [Disorder of calcium membrane transport as a common link in the pathogenesis of different forms of cardiac insufficiency]. PMID- 6243725 TI - [Mucopolysaccharide storage diseases. I. Clinical aspects and diagnosis]. PMID- 6243726 TI - Ultrastructural and cytochemical correlates of myocardial protection by cardiac hypothermia in man. AB - We report observations on ultrastructural and cytochemical changes in the myocardium after hypothermic protection in 21 patients who underwent cardiac operation. Two general categories of hypothermic protection were studied. (1) topical cooling during anoxic arrest and moderate general hypothermia (10 patients with aortic valve replacement, Group 1) and (2) intermittent perfusion during moderate general hypothermia combined with topical cooling (11 patients with multiple valve replacement, Group II). Transmural left ventricular biopsies were taken at the start of the cardiopulmonary bypass and shortly after the end of aortic cross-clamping. In Group I (cross-clamp time, 51 +/- 12 minutes) only minor pathologic changes of the myocardial fine structure were found, with no differences among the left ventricular layers. In most mitochondria, structure remained intact but the mitochondrial granules disappeared. Cytochrome-c-oxidase activity was unchanged. In Group II (total cross-clamp time, 83 +/- 16 minutes) the subendocardium was well preserved. Slight subcellular damage comparable with that of resulting from topical cooling was seen in all hearts even after a total cross-clamp period of 106 minutes. Cytochrome-c-oxidase activity was unchanged. In the subepicardium, however, a positive correlation was found between the severity of ultrastructural damage and total cross-clamp time (p less than 0.05). Matrix clearing, damage to the cristae and the mitochondrial membranes, and nuclear abnormalities occurred when the aorta was cross-clamped for morethan 60 minutes. Cytochrome-c-oxidase activities decreased in these samples. It is concluded that: (1) no significant subcellular injury was found in hearts cooled topically during 1 hour of anoxic arrest; and (2) in hearts protected by intermittent perfusion during moderate general hypothermia and additional external cooling, the subendocardium was well preserved for anoxic periods of up to 106 minutes. However, after 60 minutes of aortic cross-clamping subcellular damage increased progressively in the subepicardium. PMID- 6243727 TI - Mucoepidermoid and adenoid cystic carcinomas of the esophagus. AB - Four case reports of patients with tumors of the esophagus resembling those of salivary gland origin are presented with a review of the cases published to date. These tumors arise in the submucosal glands in the esophagus and are histologically similar to adenoid cystic and mucoepidermoid carcinomas of the salivary glands. The mucoepidermoid variety occurs more frequently in men than in women, and the adenoid cystic carcinomas are equally distributed between the sexes. In most of the cases reported the tumors were resectable but the overall survival rate is poor and is similar to the rates found with the more frequent squamous cell cancer of the esophagus. PMID- 6243728 TI - Interrelationships among insulin, glucagon, and gastric inhibitory polypeptide in insulinoma. AB - The interrelationships of serum insulin, glucagon, and gastric inhibitory polypeptide were examined in 13 patients with insulinoma during fed and fasted states. Compared with normal subjects, patients with insulinoma had significantly lower glucose and higher insulin levels during both the fed and the fasted states. Although glucagon concentration was higher at the completion of the fast in patients with insulinoma compared with normals, no significant differences were apparent during the fed state. No difference was noted in gastric inhibitory polypeptide either during the fed state or at the termination of the fast. Under the conditions of the study, no direct suppressive effect of insulin on glucagon or gastric inhibitory polypeptide secretion was apparent. In addition, as opposed to that in normals, the insulinotropic effect of glucagon did not appear to be blunted by hypoglycemia in most of the patients. After glucagon injection, all symptomatically hypoglycemic patients experienced an amelioration of symptoms and restoration of the plasma glucose into the normal range. PMID- 6243729 TI - Impairment of brain neurotransmitter receptors in aged rats. AB - Dopamine and gamma-aminobutyric acid (GABA) receptor functions have been measured in various brain areas of aged rats. [3H] Spiroperidol binding is decreased in various dopaminergic brain areas, particularly in striatum and tuberculum olfactorium. In striatum the number of binding sites for [3H] spiroperidol is similar in both groups of animals, while the affinity is reduced in senescent rats. Moreover, in the pituitary a 50% increase of [3H] spiroperidol binding was detected in the group of senescent animals. On the other hand, [3H] GABA binding is significantly decreased in substantia nigra and hypothalamus of aged rats, while it is unmodified in cerebral cortex, cerebellum, striatum and nucleus accumbens. PMID- 6243730 TI - Regulation of heme metabolism during senescence: activity of several heme containing enzymes and heme oxygenase in the liver and kidney of aging rats. PMID- 6243732 TI - Local IgA-class antibodies against respiratory viruses in middle ear and nasopharyngeal secretions of children with secretory otitis media. AB - The presence of antibodies against some important respiratory viruses in the middle ear and nasopharyngeal secretions of 52 children with secretory otitis media (SOM) was investigated in order to find out about the role of these viruses in the development of SOM. The method employed was a sensitive radioimmunoassay test. Antibodies to adeno, syncytial, and parainfluenza 3 viruses were detected in about 50%, 50% and 20% of the patients, respectively. In eight patients the middle ear secretion/nasopharyngeal secretion titer ratio of antibodies to one virus was selectively increased in comparison with the other viruses tested, indicating an active local production of specific antibodies in the middle ear. Further studies are required to determine the cause of such an active antibody synthesis and its possible role in the etiopathogenesis of SOM. PMID- 6243731 TI - A decision analysis approach to the swine influenza vaccination decision for an individual. PMID- 6243733 TI - Stimulation of glucose-6-phosphatase by polyamines is a membrane-mediated event. PMID- 6243734 TI - [Arthroscintigraphy in the diagnosis of recurrences after early synovectomy of the knee joints in rheumatoid arthritis]. PMID- 6243735 TI - [Visualization of the kidneys in skeletal scintigraphy with pyrophosphate-99mTc in lymphogranulomatosis]. PMID- 6243736 TI - Characterization of the inhibitory effect of somatostatin upon insulin and glucagon release in the isolated perfused canine pancreas: evidence for interaction with calcium. AB - Somatostatin is a potent inhibitor of insulin and glucagon release from the isolated perfused canine pancreas. The present investigation was undertaken to characterize the pancreatic effects of somatostatin by studying its ability to influence insulin and glucagon release from the same perfusion preparation in response to various well-known stimuli and modulators. Somatostatin inhibited insulin and glucagon release in all test situations chosen but one. Thus, somatostatin inhibits pancreatic hormone secretion irrespective of whether it is modulated by (1) a primary initiator of insulin release--glucose (1.3 or 8.3 mM), leucine (4.1 mM), tolbutamide (2.6 mM); (2) a potentiator of insulin release, i.e., a substance that requires the presence of glucose--arginine (1 mM); (3) substances known to increase the level of cyclic AMP (cAMP) in the islets- glucagon (2 ng/ml), cAMP (1 mM), theophylline (1 mM); (4) an autonomic agent- epinephrine (2 ng/ml), acetylcholine (10 microM); or (5) alpha and beta adrenergic antagonists--phentolamine (1 microM), propranolol (1 microM). In contrast, high Ca++ concentrations (4.8 and 8.2 mM) abolished the inhibitory action of somatostatin on both insulin and glucagon release. These findings lend support to the hypothesis that somatostatin acts at a stage of secretory processes, possibly related to Ca++ inactivation, late in the chain of events leading to hormone release. PMID- 6243738 TI - Chronic dialysis for uremia. PMID- 6243737 TI - Feline oncogenic viruses. PMID- 6243739 TI - Active transport of sodium and potassium ions: mechanism, function, and regulation. PMID- 6243740 TI - Basic science for clinicians. PMID- 6243741 TI - Collagenase in idiopathic pulmonary fibrosis. PMID- 6243742 TI - Experimental germ-cell tumors. PMID- 6243743 TI - Expression of herpesvirus-induced antigens in human cervical cancer. PMID- 6243744 TI - (ADP-ribose)n participates in DNA excision repair. AB - Chromatin proteins are covalently modified by at least five different processes; in no case has the precise physiological function been established. One of these post-synthetic, covalent modifications is effected by the enzyme poly(ADP-ribose) polymerase, which uses the coenzyme NAD+ to ADP-ribosylate chromatin proteins. The modification consists largely of mono(ADP-ribose), but long, homopolymer chains of (ADP-ribose) are also present. Various physiological functions have been suggested for (ADP-ribose)n. Here we demonstrate that one function of (ADP ribose)n is to participate in the cellular recovery from DNA damage. Specific inhibitors of poly(ADP-ribose) polymerase prevent rejoining of DNA strand breaks caused by dimethyl sulphate and cytotoxicity is enhanced thereby. The rejoining of strand breaks is prevented also by nutritionally depleting the cells of NAD. PMID- 6243745 TI - Cellular site of opiate dependence. AB - Experiments on whole animals, guinea pig isolated ileum, individual neurones in situ and cultured neuroblastoma--glioma hybrid cells indicate that opiate dependence and associated tolerance develop within neurones bearing specific opiate receptors (opiate-sensitive neurones). The essential change appears to be an hypertrophy of the cyclic AMP system, in response to inhibition by opiate of a neuronal adenylate cyclase. PMID- 6243746 TI - Evidence for two populations of excitatory receptors for noradrenaline on arteriolar smooth muscle. AB - We have recorded the responses of arteriolar smooth muscle cells to iontophoretically applied noradrenaline. Records of both muscle movement and muscle membrane potential were made. We found that two distinct types of response could be detected, depending on the position of the noradrenaline micropipette. One type of response consisted of a localised constriction near the noradrenaline source: this effect could be abolished by the alpha-antagonist phentolamine and was not associated with a change in arteriolar membrane potential. The other type of response was a depolarisation similar to the excitatory junction potentials (e.j.ps) produced by sumpathetic nerve stimulation. These observations suggest that there are two populations of receptors for noradrenaline on arterioles, and could explain the paradoxical failure of alpha-antagonists to block neuromuscular transmission at some sutonomic end organs such as the vas deferens, arteries and arterioles. PMID- 6243747 TI - A novel fragment of the corticotropin-beta-lipotropin precursor. PMID- 6243748 TI - Sequence of the human insulin gene. AB - The human insulin gene contains two intervening sequences, one is within the region transcribed into the 5'-untranslated segment of the mRNA and the other interrupts the C-peptide encoding region. A comparison of the human with the rat insulin genes indicates potential regulatory regions in the DNA segment preceding the gene and suggests that the ancestral form of the insulin gene had two intervening sequences. PMID- 6243749 TI - Synaptic mechanisms involved in responses of chromaticity horizontal cells of turtle retina. PMID- 6243750 TI - Metastatic potential correlates with enzymatic degradation of basement membrane collagen. PMID- 6243751 TI - Phorbol ester-mediated stimulation of the synthesis of mouse mammary tumour virus. PMID- 6243752 TI - Influence of local vascularity on hormone receptors in mammary gland. AB - Procedures, such as teat removal (thelectomy) or teat duct ligation, which prevent removal of milk, lead to rapid involution of the lactating mammary gland; performed unilaterally they have been used previously to study the biochemistry of involution, enabling a comparison of normal and involuting glands in the same animal against the same systematic hormonal environment. Both the protein hormone prolactin and the steroid hormone oestrogen are of importance in the development and function of the mammary gland. In the present experiments, female Sprague Dawley rats were unilaterally thelectomised and the binding to the mammary gland of prolactin and oestrogen was examined through pregnancy, lactation and weaning. There was an effect of thelectomy during lactation only, when levels of both receptors increased in the intact lactating gland but failed to rise in the thelectomised, involuting gland. Capillary closure is known to occur in the mammary glands of rats after 36-48 h of milk accumulation. The rate of delivery of hormones to the tissue will be drastically reduced and it is concluded that this, rather than systemic hormone levels, is of importance in controlling receptor levels. PMID- 6243753 TI - Novel expression-linked copies of the genes for variant surface antigens in trypanosomes. AB - Pathogenic African trypanosomes evade the immune system of their mammalian hosts by the sequential expression of alternative cell-surface glycoproteins (reviewed in refs 1,2). Variant surface glycoproteins (VSGs) purified from cloned variants of Trypanosoma brucei have similar molecular weights (about 60,000), but differ in amino acid composition, N-terminal amino acid sequence and C-terminal structure. We have cloned DNA complementary to the messenger RNA's for four immunologically distinct VSGs and hybridised these complementary DNAs (cDNAs) with restriction digests of T. brucei nuclear DNA, fractionated by gel electrophoresis and transferred to nitrocellulose strips. Each cDNA recognises a unique set of fragments and this basic set is present unaltered in the nuclear DNAs from the four variants. In addition, each probe recognises an extra fragment only in nuclear DNA isolated from cells expressing the VSG corresponding to the cDNA probe. We infer that activation of a VSG gene involves the production of an expression-linked copy of that gene. PMID- 6243754 TI - Prostaglandins and kidney erythropoietin production. PMID- 6243755 TI - Incidence and clinical importance of renal tubular defects in recurrent renal stone formers. AB - Renal tubular function was studied in 318 consecutive recurrent renal stone formers. Impaired acidification capacity was found in 19% of the patients, and tubular proteinuria in 13% of the patients. Most of the patients with defective acidification of the urine had the incomplete form of renal tubular acidosis (RTA), rpoximal and distal defects being equally common. The incidence of impaired acidification was much higher in the female (38%) than in the male (13%) stone formers. A further analysis of the clinical picture in patients with acidification defects revealed a more severe stone disease than among other stone formers. Characteristic findings were an early onset, multiple recurrences were an increased need for surgery. Stone analyses showed a high frequency of calcium phosphate stones. Investigations of renal tubular functions appear to be a valuable adjunct in the evaluation of recurrent renal stone disease. PMID- 6243756 TI - Reevaluation of the pituitary-adrenal response to ether in rats with various cuts around the medial basal hypothalamus. AB - ACTH release elicited by ether inhalation or ethervenesection and measured by changes in plasma corticosterone level was studied in rats at various time intervals after placing a complete or an anterolateral cut around the medial basal hypothalamus (MBH). There was no rise in 'resting' plasma corticosterone after acceptable isolations and, in 5 out out of 6 series of experiments, the complete or long anterolateral cuts prevented the rise in plasma corticosterone normally induced by ether stress. In contrast, ethervenesection elicited a significant increment of plasma corticosterone when the basal region of the lateral retrochiasmatic area (RCAL) was not completely transected. Possible reasons why these experiments failed to confirm previous findings are discussed. These results support the hypothesis that corticoliberin-containing fibers enter the MBH from outside and that most of these fibers run through the RCAL on their way towards the neurohemal regions of the infundibulum. PMID- 6243757 TI - Fourth Geoffrey Harris Memorial Lecture: The hypophysial portal circulation today. PMID- 6243758 TI - Release of corticotropin and corticotropin-releasing factors from rat posterior pituitary in vitro. AB - Electrical stimulation of rat posterior lobes in vitro inhibited bioactive corticotropin (ACTH) release from the intermediate lobe and promoted the release of corticotropin-releasing factor(s) (CRF). Both effects were calcium dependent. Released posterior lobe CRF was inactivated by thioglycolate, and the CRF activity could be accounted for by vasopressin. Results suggest strongly that vasopressin is the predominant CRF released from neurohypophysial axons, and that intermediate lobe ACTH release is submitted to an inhibitory control. PMID- 6243759 TI - Section of the pituitary stalk in the rhesus monkey. II. Morphological studies. AB - The effects of pituitary stalk section on anterior pituitary morphology were studied in 18 female rhesus monkeys. 4 animals were studied within 1--14 days after the operation, while the others were examined later (average 17.2 months). In 3 monkeys there was no necrosis of the anterior lobe, whereas in the remaining animals, an area of infarction averaging 20% was found. Using immunocytochemical techniques, we found that corticotropes and somatotropes were still present following the procedure, and that the number of lactotropes increased markedly. In contrast, gonadotropes, although present in the pars tuberalis, were no longer demonstrable in the pars distalis 3 weeks after stalk section. These results show remarkable agreement between endocrine studies and morphological observations, and indicate a variable degree of dependency of the various pituitary cells on central nervous system influences. PMID- 6243760 TI - The effects of acute and chronic ethanol administration on twitch and tetanic force production by rat gastrocnemius muscle in situ. AB - The effects of acute ethanol injection on force production were measured in normal and chronic alcoholic rats. Acutely injected normal rats, acutely injected chronic alcoholic rats, and noninjected chronic alcoholic rats were compared with control groups: normal nonalcoholic rats and a dietetically deprived control group. Acute ethanol injection increased twitch force in normal rats but not in chronic alcoholic rats. Chronic alcohol ingestion caused a decrease in maximal twitch and tetanic tension. The dietetically deprived control group developed less maximal tetanic force, with no significant decrease in maximal twitch force. Chronic alcohol ingestion seemed to decrease maximal twitch tension, whereas the decrease in maximal tetanic could be attributed to the effects of malnutrition. PMID- 6243761 TI - Effects of epinephrine, ouabain, and insulin in experimental autoimmune myasthenia gravis. AB - To gain a clue to the target of anti-AChR antibody, rats with acute and chronic experimental autoimmune myasthenia gravis (EAMG) that was induced by immunization with Narke anti-acetylcholine receptor (AChR) were studied using agents acting on active Na-k transport. Postsynaptic response to epinephrine was defective in chronic EAMG with high titers of antibody, suggesting that active Na-K transport system modulated by cyclic adenosine monophosphate (AMP) may be affected primarily by antibody. Sensitivity to ouabain was less than normal in acute EAMG and became close to normal when treated with anticomplementary factor. Findings suggest that acute EAMG is a case of functional denervation. Normal response to insulin occurred in all phases of EAMG. PMID- 6243762 TI - Neuropsychologic impairment in astrocytoma survivors. AB - Thirteen patients selected for long-term survival with primary astrocytic tumor (who failed to return to premorbid educational or vocational levels) were examined by neuropsychologic tests of specific and generalized higher cortical functions. In the absence of tumor regrowth or other neurologic disorders, each demonstrated difficulty in problem solving or coping with novel situations when previously acquired abilities, overlearned material, and psychometric intelligence appeared consistent with their premorbid level. The diffuse difficulties were unrelated to tumor type or location, and were not explicable by existing focal deficits, psychotic or depressive thought disorders, metabolic difficulties, or hydrocephalus. These examinations explained in part why these patients failed to resume active social lives or premorbid employment. The diffuse cortical dysfunction was most notable on the Category Test, Trails B, and Localization component of the Tactual Performance Test. PMID- 6243763 TI - Multiple cranial neuropathies, trigeminal neuralgia, and vascular headaches in sickle cell disease, a possible common mechanism. AB - Patients with sickle cell disease are subject to a variety of neurologic complications. A patient with sickle cell disease and rarely noted features or complications is described. The association of abnormal (sickle-type) hemoglobin (Hgb S) with trigeminal and facial neuropathies and vascular headaches appeared to coincide with reactivation of the hematologic disease. PMID- 6243764 TI - Intrauterine viral infection and the cell-mediated immune response. AB - In 8 of 23 infants with congenital central nervous system (CNS) anomalies, we observed an increased cell-mediated immune (CMI) response (lymphocyte blastogenesis) to one of six simultaneously tested viral antigens, without detection of concomitant elevation in humoral antibody to that virus. These data suggest possible intrauterine viral exposure in a significant number of anomalous infants and a possible role of that exposure in the pathogenesis of congenital CNS anomalies. The CMI response may offer another approach to the identification of etiologic agents of a significant number of birth defects. PMID- 6243765 TI - [Recent etiopathogenic acquisitions concerning bronchial asthma]. PMID- 6243766 TI - Comparative study of diagnostic procedures for congenital cytomegalovirus infection. AB - In a prospective study the incidence of congenital cytomegalovirus (CMV) infection was 2.2% (31 OF 1,412) as evidenced by viruria during the first week of life. Among immunoserologic methods used to screen these neonates, the rheumatoid factor test, although non-specific, proved to be the most convenient; its sensitivity for identifying infants with CMV infection was 35% to 45% with no false-positives. The rates for correct and incorrect identification of neonates at risk was, respectively, 33% and 3.1% when testing for increased levels of IgM; 5% and 10% when testing for increased levels of IgA; 76% and 21% when testing for IgM anti-CMV (IgM immunofluorescent test) antibody, and 0% when testing for IgA anti-CMV antibody. Rapid virologic diagnosis was achieved by assessing urine specimens. Confirmation by electron microscopy was possible in less than one hour in 92% of cases. The detection of early induced CMV-specific nuclear antigens by anticomplement immunofluorescence was diagnostic in 91% of cases within one day of inoculation of specimens in tissue culture. Infectivity of CMV in urine was well preserved for a least seven days at 4 C. Thus, in order to achieve a rapid diagnosis of congenital CMV infection, in sick as well as asymptomatic neonates, urine specimens may, if necessary, be transported at 4 C to distant laboratories. PMID- 6243768 TI - West syndrome and Lennox-Gastaut syndrome: a survey of natural history. AB - The West syndrome and the Lennox-Gastaut syndrome are characterized by their onset in infancy and early childhood, intractable seizures occurring almost daily, severe psychomotor retardation, and poor prognosis. Among handicapped children, they offer the most serious problems in daily care at home or in institutions because of frequent attacks and marked retardation. A nationwide survey in Japan was performed to elucidate the natural history of these two syndromes. PMID- 6243767 TI - Concentration of human chorionic gonadotropin in the cerebrospinal fluid of patients with germinal cell hypothalamic tumors. AB - Plasma and cerebrospinal fluid (CSF) specimens were measured simultaneously for human chorionic gonadotropin (HCG) in two patients with HCG-secreting choriocarcinoma. In the patients with hypothalamic tumors, the CSF HCG levels were higher than the plasma HCG concentrations. In the patient with gestational choriocarcinoma with no known cerebral metastases, the plasma HCG level greatly exceeded the CSF HCG concentration. The finding of a CSF HCG concentration that approaches or exceeds the plasma value would be a useful screening procedure in localizing a pathologic source of HCG secretion in patients with a suspected hypothalamic tumor. An unexpected finding in the patient who also had a hypothalamic embryonal cell carcinoma and hypocortisolism was an extremely high concentration of a biologically inactive adrenocorticotropic like substance in the CSF. PMID- 6243769 TI - Fatal cytomegalovirus bronchiolitis in a patient with Nezelof's syndrome. AB - A 4-year-old girl who had received a fetal thymus gland by intraperitoneal transplantation 41 months previously sustained acute, fatal bronchiolitis due to culture-proven cytomegalovirus despite the fact that a specific antibody response to this organism was detected. While the thymic transplantation had increased the number of circulating T lymphocytes and had permitted immune sensitization to delayed-hypersensitivity skin test antigens, there was still an incomplete state of T lymphocyte function. In particular, isolated lymphocytes failed to respond to stimulation with phytohemagglutinin at several concentrations and, more important, the pathologic examination demonstrated a severe anatomic deficiency of lymphoid tissue associated with T lymphocyte function. The unusual infection that caused the death of this child emphasized the necessity of acquiring sufficient T lymphocyte function in immunologic reconstitution attempts. PMID- 6243770 TI - [Carcinomas of the nasopharynx. Relationship between histological type and anti Epstein-Barr virus serology (author's transl)]. AB - This study was aimed at the comparison of values of anti-Epstein-Barr virus serology in different groups of patients suffering from carcinoma of the nasopharynx (NPC), classified according to histological type defined by the new classification of the WHO. A group of patients with other tumours of the upper respiratory and digestive tract was used as a control. Antibody levels were high in patients with undifferentiated carcinomas whilst they were low in the controls. In patients with differentiated carcinomas antibody levels were most often equivalent to those of the controls, even though high values were sometimes seen. These findings would appear to offer evidence that the new histological classification of NPC is well founded, and to a certain extent reflect the epidemiological, clinical and therapeutic classifications already seen for these two types of carcinoma. PMID- 6243771 TI - [Trigeminal sensory involvement in Bell's palsy (author's transl)]. AB - Trigeminal sensory involvement was noted in 14 out of 24 cases of Bell's palsy. The authors describe its characteristics and its chronology with regard to the facial paralysis. Then they propose a vascular mechanism for this association on the basis of two kinds of data. First it is known that there is a common arterial supply of the VIIth and Vth cranial nerves through the middle meningeal vascular system. Secondly some exceptional complications of embolisation within that system have included involvement of both VIIth and Vth sensory nerves. These facts support the vascular basis of Bell's palsy and present an example of a vascular territorial pathology in cranial nerve involvement. PMID- 6243772 TI - [Echotomography of renal tumours. Diagnostic value (author's transl)]. AB - One hundred tumours were detected by IV urography and studied by echotomography. In 37 cases, a nephrotomography was performed and in 65 cases a renal arteriogram. The reliability of these three examinations was analysed. Three calcified masses were impossible to analyse by echography and required arteriography from the outset. There were two false negatives related to an error of interpretation and not to any defect in the echography. With regard to the 3 calcified masses, no better information was obtained by nephrotomography. Four necrosed carcinomas were erroneously identified as cysts. Four carcinomas were missed at arteriography. The reliability of echotomography was good apart from in cases of small carcinomas (less than 2 cm) and calcified masses. It proved to be more reliable than nephrotomography and arteriography. By contrast, it was less selective since there were false positive results in 13% of cases. PMID- 6243773 TI - [Anti NADases in streptococcal infections (author's transl)]. PMID- 6243775 TI - The detection of DNA-binding proteins by protein blotting. AB - A method, called "protein blotting," for the detection of DNA-binding proteins is described. Proteins are separated on an SDA-polyacrylamide gel. The gel is sandwiched between 2 nitrocellulose filters and the proteins allowed to diffuse out of the gel and onto the filters. The proteins are tightly bound to each filter, producing a replica of the original gel pattern. The replica is used to detect DNA-binding proteins, RNA-binding proteins or histone-binding proteins by incubation of the filter with [32P]DNA, [125I]RNA, or [125I] histone. Evidence is also presented that specific protein-DNA interactions may be detected by this technique; under appropriate conditions, the lac repressor binds only to DNA containing the lac operator. Strategies for the detection of specific protein-DNA interactions are discussed. PMID- 6243774 TI - Restriction and modification enzymes and their recognition sequences. PMID- 6243776 TI - Transcription of the viral genome in cell lines transformed by simian virus 40. I. Mapping of virus-specific nuclear RNAs. AB - Mapping of virus-specific nuclear transcripts was carried out in three lines of rat cells transformed by SV40. Each of these cell lines contained a single copy of integrated viral DNA with identified regions adjacent to cell DNA (1). The main virus-specific nuclear transcript in all of these cell lines was shown to be complementary to the minus strand of the early region in SV40 genome. Each cell nucleus contained approximately 50 copies of these RNAs. Transcripts complementary to both strands of the late region in viral genome were also detectable in all of these cell lines. Its content varied depending on the cell line and was 20-50-fold less than that of the main virus-specific transcript. All the regions of integrated SV40 genome in isolated nuclei of transformed cells were equally sensitive to pancreatic DNase I treatment suggesting that the whole viral genome served as a template for RNA synthesis in these cell lines. PMID- 6243777 TI - The ovalbumin gene-sequence of putative control regions. AB - We present the sequence of regions of the chicken ovalbumin gene believed to be important in the control of initiation of transcription, splicing, and transcription termination or polyadenylation. Comparison with corresponding areas of other genes reveals some homologous regions which might play a role in these processes. PMID- 6243778 TI - Evidence for the role of double-helical structures in the maturation of simian virus-40 messenger RNA. AB - Simian Virus-40 infected BSC-1 cells were pretreated with glucosamine and briefly pulsed with [3H]-uridine. The labeling can be halted instantaneously by the addition of cold uridine and glucosamine. Under these pulse-chase conditions, the inhibitory effects of the intercalating agent proflavine on the processing of prelabeled nuclear RNA precursors were examined in vivo. Proflavine inhibits the cleavage of viral nuclear RNA precursors. However, turnover of the mature viral mRNAs in the cytoplasm is not inhibited. The effect of proflavine on processing is not a secondary consequence of its inhibition of protein synthesis. The data suggest that base-paired secondary structures in the primary transcripts are important processing signals in the generation of viral mRNA molecules. PMID- 6243779 TI - A spite specific endonuclease from thermus thermophilus 111, Tth111I. AB - A site specific endonuclease with novel specificity has been isolated from Thermus thermophilus strain 111 and named Tth111I. Tth111I cleaves lambda DNA into three fragments of 23.5, 25.7 and 50.8% of the total length, and ColE1 DNA into two fragments of nearly equal length. The sequences around Tth111I cleavage sites of ColE1 and lambda DNA were determined by the Maxam and Gilbert method and the two dimensional mapping method. The results suggest that Tth111I recognizes the DNA sequence (formula: see text) and cleaves the site as indicated by the arrows. Assuming that the first T.A pair in the sequence can be replaced for any base pair, the Tth111I recognition sequence has the symmetry with the two-fold axis as most type II restriction endonucleases do. PMID- 6243780 TI - Nuclear RNA transcripts from Drosophila melanogaster ribosomal RNA genes containing introns. AB - The transcription of ribosomal genes in a cell line (Kc) derived from female D.melanogaster, has been investigated using hybridization probes prepared from restriction fragments of a cloned rDNA repeat with a 5 kb type I [Wellauer et al. (1978) Cell 14, 269-278] intron. Gels, of nuclear RNA that have been transferred to diazotized paper and hybridized with labelled intron sequences, reveal both large (1-10 kb) transcripts and a discrete 325 base species. Berk-Sharp experiments [(1977) Cell 12, 721-732] reveal large transcripts that are homologous to intron sequences and extend into 28S sequences as well. However, while the abundance of 28S transcripts is about 50,000 copies per nucleus [Clark et al. (1977) Genetics 86, 789-800], these long transcripts are only present at 1 2 copies per nucleus and the 325 base species is only 10 times more abundant. In view of the fact that female cells have about 400 rDNA genes, 49% of which have type I introns, one must conclude either that transcription rarely occurs from the genes containing introns (the majority) or these transcripts are processed unusually rapidly. Transcripts homologous to the "non-transcribed spacer" region have been found, but their abundance is no higher. PMID- 6243782 TI - Maturation of ovarian follicles: actions and interactions of pituitary and ovarian hormones on follicular cell differentiation. PMID- 6243781 TI - Control of hepatic glycogenolysis. PMID- 6243783 TI - Hydroxyapatite deposition disease. AB - Hydroxyapatite crystals are a common cause of periarticular disease, but recent studies have shown that they may also be deposited intra-articularly, either as a primary phenomenon or secondary to another disease. A continuum of abnormalities from monoarticular periarthritis to polyarticular disease and finally joint destruction may occur. PMID- 6243784 TI - [Bacteriophage lambda integration into host chromosome (biochemistry of Int protein and pleiotropic effects of host factors) (author's transl)]. PMID- 6243785 TI - Current status of breast cancer chemotherapy in Japan. AB - Recent advances in breast cancer chemotherapy are reviewed with special regard to the characteristics of the disease in Japanese women, which has a low incidence rate and favorable prognosis. Long-term administration of a single drug such as cyclophosphamide (CY) was most widely used with an acceptable response rate and prolongation of survival in metastatic disease. Combination chemotherapy, mostly including mitomycin C (MMC), 5-fluorouracil (5-FU), and CY in the regimen, produced a higher response rate than single-drug treatment. Surgical adjuvant chemotherapy with MMC and CY, single or in combination, was usually beneficial for the patients in moderately advanced stages of disease but was inadequate for those in more advanced stages. Significance of estrogen receptor is discussed in relation to responsiveness to chemotherapy. Breast cancer chemotherapy in Japan includes some aspects different from those in western countries. PMID- 6243786 TI - Present status of lung cancer chemotherapy in Japan. PMID- 6243787 TI - [Combined arteriovenous dysplasia and disturbed osseous growth (author's transl)]. AB - Basing on own observations by the authors in 10 patients with angiodysplasia and circumscribed gigantism of an extremity, typical phlebographic and arteriographic findings are described. Classification of the angiodysplasia of the Klippel Trenaunay and F. P. Weber type is in accordance with suggestions advanced in recent literature. The x-ray methods required for the purpose of establishing the diagnosis, are described. PMID- 6243788 TI - Properties of a normal mouse cell DNA sequence (sarc) homologous to the src sequence of Moloney sarcoma virus. AB - A 15.0-kilobase (kb) Eco RI DNA fragment from normal mouse Balb/c genomic DNA that contains sequences (sarc) homologous to the acquired cell sequences (src) of Moloney sarcoma virus (MSV) has been cloned in phage lambda. The sarc region (1.2 to 1.3 kb) of the 15.0-kb cell fragment is indistinguishable from the src region of two isolates of MSV as judged by heteroduplex and restriction endonuclease analyses. The cellular sequences flanking sarc show no homology to other MSV sequences. Whereas cloned subgenomic portions of MSV that contain src transformed NIH-3T3 cells in vitro, the cloned sarc fragment is inactive. PMID- 6243789 TI - [Adjuvant chemotherapy in treatment of non seminomatous germinal testicular tumor. Results and reflexions about 77 cases (author's transl)]. AB - To define prognostic factors of testicular cancer and to develop a strategic therapy based on clinical, pathological and biological findings, 77 cases of non seminomatous testis tumor, observed in G.F. Leclerc Center from 1967 to 1977, have been analysed. For all these patients early chemotherapy program was associated with surgery; radiation therapy was reserved for stages with retroperitoneal metastatic disease. Results of this review confirmed the interest of such medical treatment which improved survival in all stages of disease. Some prognostic factors could be detailed from these cases: nature of tumoral components, invading of lymph node, presence or not of biological markers; identification of these would unable us to choose the best adjuvant chemotherapy program and to define its place in the management of testis tumor's treatment. PMID- 6243790 TI - [Electrologic syndromes of alteration of elicited blink reflex in multiple sclerosis. Study of a group of 33 patients (author's transl)]. AB - The study of the blink reflex, performed in a group of 33 patients with multiple sclerosis show, as Kimura (1970) and Namerow (1973) had established, the high frequency of its alterations in this disease (almost half of the cases). The alterations of blink reflex don't depend on duration of illness; if it is true that the alterations of blink reflex are more often observed in patients with clinical symptoms of involvement of brain-stem (and particularly of pons), in some cases, only the alteration of the blink reflex suggests a brain-stem's lesion and helps to establish the diagnosis. The diversity of sites of lesions induced by multiple sclerosis in the brain-stem explains the diversity of blink reflex alteration's syndromes since they correspond to the (almost) totality of the semiology of blink reflex. PMID- 6243791 TI - [Thyroid nodules. A report on 320 cases (author's transl)]. AB - An analytical study of 320 case reports of patients with one or more thyroid nodules, 246 of whom had been operated upon, revealed the presence of 32 cancers, 15 toxic nodules, and 195 inactive benign uni- or multilobular goitres. Complementary examinations (scintigraphy with technetium, thermography, ultrasonography) cannot definitely establish the benign nature of a nodule. As long as cytological examination after needle biopsy, which requires the services of a highly specialised cytologist, will not become a routine procedure, histological examination is essential for correct diagnosis. Any nodule should be excised, therefore, and the thyroid explored completely. PMID- 6243792 TI - [Diagnosis of chyliferous blockage by the hyperlipidemia test (author's transl)]. AB - In our hyperlipidemia test, the total lipids curve, a plateau without a postprandial peak, allows an easy diagnosis of the chyliferous blockage. The malformation of chyliferous vessels produces the congenital forms: exsudative enteropathy, chyloperitoneum, spontaneous chylothorax, chylous cyst of the mediastinum, reflux of chyle in the pulmonary lymphatics, lymphoedema with chyle reflux in the lymphatics of the leg and chyluria. The acquired forms comprise the post-infectious sclerosis of the intestinal lymphatics and the neoplastic invasions of the mesenteric lymph nodes. The optical density curve brings some informations for a better understanding of lipid's absorption. PMID- 6243793 TI - [Surgical treatment of pulmonary round foci detected in one male and eight female patients with breast cancer. Solitary metastasis, a second primary bronchopulmonary cancer or benign round foci? (author's transl)]. AB - Pulmonary dissemination of breast cancer is frequent in those patients who have died of the disease and in those survivors who have not been cured after removal of the breast and X-ray treatment in the advanced states of the disease. When the metastases are identified, they are almost always multiple and bilateral. The appearance of a solitary, late pulmonary coin lesion (metachrone) in someone with breast cancer certainly suggests a pulmonary metastasis, but in fact, it is more likely to be a second cancer than a metastasis, that is, a primary bronchopulmonary cancer. The presence of a solitary pulmonary coin lesion in someone who has or who has had breast cancer, presents therefore certain particular problems. After having controlled by xerotomography or CAT that there is no pulmonary diffusion in either lung, that there is no invasion of other tissues or organs, and after having controlled locally around the breast cancer, then it is imperative to remove the lesion without delay since it is certainly malignant and most probably a second cancer, that is a primary broncho-pulmonary cancer, an adenocarcinoma, detected at an asymptomatic stage. the prognosis of a broncho-pulmonary adenocarcinoma, depends on the precocity of its removal. PMID- 6243794 TI - [Osteomalacia following uretero sigmoidostomies (author's transl)]. AB - Surgical anastomosis of the ureter in the sigmoid could lead to osteomalacia. The pathogenesis of this disease is rather complicated and involves several factors, the most important of which is hyerchloremic acidosis associated with modifications of transport across the intestinal lining, and in particular, the elimination of bicarbonates and the reabsorption of H+ ions. This systemic acidosis makes the calcium balance negative by mobilizing calcium bicarbonate from bone and possibly by inhibiting alkaline phosphatase activity. The role of PTH and vitamin D has yet to be satisfactorily explained. The authors present cases of osteomalacia following two uretero-sigmoidostomies, one for bladder exstrophy and the other after bladder removel for tumour. The physiopathological mechanisms of osteomalacia are briefly recalled together with indications of treatment. PMID- 6243795 TI - [Amputation stump pain: a therapeutic study (author's transl)]. AB - A study has been done in a Thermal Army Hospital, concerning the suffering of amputed persons and their treatment by "tiapride". For 20 observations, it has been noted 11 excellent and 6 good results, by a mean treatment of 300 mg. Interesting results are particularly observed at the first appearance of the soreness, a better integration of this one has been proved, it has also been noticed that amputed patients tolerate much better their prosthesis. PMID- 6243796 TI - [Triple and quadruple cancers (author's transl)]. AB - The authors report two cases of multiple cancers (three and four) and precise the criterions of multiplicity of cancers, their frequency and their localizations. The factors incriminated in multiple carcinogenesis, often not well known and complicated, are also studied, such as family ground, age, blood groups, hormones, viruses, immunologic deficiencies and some carcinogenic drugs. Moreover, the actual progress in therapy, leading to the healing of the first tumor, may favour the secondary supervening of one or more cancers, as the survival is longer. PMID- 6243797 TI - [Pseudo-Volkmann syndromes]. PMID- 6243798 TI - [Serum uric-acid and serum lipids. Statistical correlations. Report of 1 000 cases (author's transl)]. AB - Distribution and correlations of serum uric-acid, cholesterol, triglycerides and lipoproteins were sought in this paper. Blood triglycerides and blood cholesterol in males were found significantly higher in patients with hyperuricaemia than in normo-uricaemic subjects. This elevation was reflected in the electrophoresis by a significant elevation of the beta and pre-beta lipoproteins correlated with hyperuricaemia. Partial correlations between age and serum uric-acid have been also demonstrated. PMID- 6243799 TI - [Leukemic infiltration and adenocarcinoma of the prostate gland (author's transl)]. AB - The appearance of a leukemic infiltration of the prostate gland as the first manifestation of a chronic lymphocytic leukemia, followed by an adenocarcinoma of the prostate gland, is exceptional, since only one case has been previously documented. For this reason the authors wish to signal the possibility of a prostatic infiltration in the course of chronic lymphocytic leukemia and insist on the association of this type of leukemia and cancer. PMID- 6243800 TI - [Complex pulmonary tumor: pneumoblastoma. A case study (author's transl)]. AB - The authors report a new case of pneumoblastoma concerning a 63 years old man who dies with hepatitic insufficiency and massive metastasis. The study in optic and electronic microscopy shows the three cellular contingents which form the pneumoblastoma: clusters of indifferenciated cells, spindle cells and cubic or cylinder epithelial cells, with few secretory granules and microvilli which form tubes or lobules. All the features show clearly a blastematous character very similar to a foetal lung which allows to differenciate the pneumoblastoma from carcinosarcoma. PMID- 6243801 TI - [Cholangio-carcinoma arising in Caroli's disease (author's transl)]. AB - Report of one case of Caroli's disease (congenital ectasy of segmental intra hepatic bile ducts) associated with congenital hepatic fibrosis, in which arised clear cell biliary carcinoma. This event seems to be very rare. In our case, the bile duct dilatation was associated with renal polycystic diseases. PMID- 6243802 TI - [Drugs and indications for medical treatment in Parkinson's disease (author's transl)]. AB - The authors present a review of the actual drugs efficient in the treatment of Parkinson's disease. They emphasize the frequency of the side-effects and consequently to the difficult management of Parkinsonism. The indications are schematically summed up. PMID- 6243803 TI - [Complications of adrenal angiography (author's transl)]. AB - Since new ways of radiodiagnostic exploration of the adrenal glands are now performed, it is important to take stock upon the complications of adrenal angiography. These complications are very different according to the fact that we explore pheochromocytomas or not. The complications of stimulation, of hypertensive accident or collapsus are quite specially observed during the angiography of pheochromocytomas. They must be prevented by a selection of the indications and a reanimation pre and per angiography. Lesions of glandular destruction that lead to a hormonal insufficiency (sometimes therapeutic) are observed outwards pheochromocytomas. Because they depend upon the explored adrenal lesion and specially of the angiographic conditions of the exploration, these complications must be prevented by a rigorous technic. PMID- 6243804 TI - [Human erythrocyte protein kinases (author's transl)]. AB - Cyclic AMP dependent and independent protein kinase activities are present in membrane as well as cytosol of human erythrocyte. Red cell membrane contains at least: 1) a cAMP dependent histone kinase type I using ATP as phosphoryl donor; 2) a cAMP independent casein kinase using ATP or GTP as phosphoryl donor; this kinase probably phosphorylates erythrocyte spectrin. In lysate of human red cell there are two or three cAMP dependent protein kinase type I and II and one cAMP independent casein kinase. Characteristics of these protein kinase activities are reviewed. Membrane substrates are numbered taking into account that the activity assays are often of dubious value. Several phosphorylation abnormalities previously reported in hematologic and non-hematologic disorders are still uncertain and at present time not any red cell protein kinase deficiency has been demonstrated. PMID- 6243805 TI - [Progression of drug addiction in France (author's transl)]. AB - Almost inexistent in France in 1965, drug addiction, especially to haschih, has since increased in an exponential manner from year to year, with devastating effects in young people. There are no "soft" drugs that can be accepted and "hard" drugs that should be banned, but just drugs that destroy personnality in a more or less rapid manner. This scourge affects mainly young people aged between 16 and 25 years and of all social levels. This tendency can only be reversed by preventive measures which include wide diffusion of all necessary information. PMID- 6243806 TI - Opportunistic pneumonias. PMID- 6243807 TI - [Aujeszky's disease: vaccination problems and vaccination advice]. PMID- 6243808 TI - [Effect of colloidal 198Au on cell cultures of human tumors (author's transl)]. AB - The authors observed the effect of colloidal 198Au on the morphology of cells in 19 cell cultures of human tumors. Partly, there were typical modifications. The reactions of the individual cells were different and the radiosensibility and dependence on the dose seemed to vary with different concentrations of the radiogold. The importance of this study with regard to clinical problems is discussed. PMID- 6243809 TI - Is renal transplantation involved in post-transplantation liver disease? A prospective study. AB - Various lesions of the liver commonly observed in renal transplant recipients are usually considered as a consequence of the transplantation procedures (immunosuppression, drug toxicity, alteration of immune responses to various viruses). A group of 64 patients all treated with corticosteroids and azathioprine was studied prospectively, and serial liver biopsies were performed on the day of transplantation and at 1 and 3 years after transplantation. Chronic hepatitis was already present in 40% of the patients on the day of transplantation and an increase of only 15% in the frequency of this condition was observed 3 years later. The presence of HBsAg in 45% of the patients at the time of transplantation was significantly associated with liver lesions. In about 3% of the cases, transplantation was directly responsible for a liver disease (peliosis hepatitis). During the followup period an evolution from chronic persistent hepatitis to chronic active hepatitis was observed with an abnormally high frequency (25%). We conclude that most of the liver diseases observed in transplant recipients are the consequence of events before transplantation and probably related to hemodialysis. PMID- 6243810 TI - [Granular cell myoblastoma. A case report involving the larynx]. PMID- 6243811 TI - [Prevention of thrombosis by thrombocyte inhibitors. 1. Cell regulation mechanisms and pharmacological modification]. PMID- 6243812 TI - [Protective action of inactivated adjuvant IBR vaccine against experimental infection in cattle]. PMID- 6243813 TI - Louping-ill virus infection of pigs. PMID- 6243814 TI - Oral fluid replacement by a glucose glycine electrolyte formulation in E coli and rotavirus diarrhoea in pigs. AB - A glucose glycine electrolyte solution (GGES) was investigated to determine its suitability for oral rehydration in diarrhoea in pigs. Piglets with diarrhoea following experimental infection with eneteropathogenic Escherichia coli were given access in cube drinkers to either GGES or water. The mortality in the GGES group (11.6 per cent) was significantly (P less than 0.05) less than in the controls (24.0 per cent), and weight gain in severely diarrhoeic piglets was greater in the GGES group. Gnotobiotic piglets were challenged with pig rotavirus and either given access to GGES or milk. The GGES was either in restricted volume or ad lib. Restricted access to GGES prevented much of the weight loss due to the diarrhoea and ad lib access to GGES allowed relatively uninterrupted weight gain in comparison with controls. In naturally occurring cases of diarrhoea on farms, access to GGES reduced mortality to weaning from 19.7 per cent to 7.2 per cent (P less than 0.05). Weight gain per day was also greater in piglets which scoured for three days or more, indicating the rehydrating effect in reducing net fluid loss. Thus GGES treatment was of value in treatment e&ects of diarrhoea due to either E. coli or rotavirus. PMID- 6243815 TI - The synthesis of glycoproteins in human melanoma cells infected with varicella zoster virus. PMID- 6243817 TI - Effect of inhibition of DNA synthesis on Epstein--Barr virus induction by tumor promoters. PMID- 6243816 TI - Viral DNA synthesis is required for the efficient expression of specific herpes simplex virus type 1 mRNA species. PMID- 6243818 TI - Temperature-sensitive kinase activity associated with various mutants of avian sarcoma viruses which are temperature sensitive for transformation. PMID- 6243819 TI - The nonstructural components of polyproteins encoded by replication-defective mammalian transforming retroviruses are phosphorylated and have associated protein kinase activity. PMID- 6243820 TI - Comparative examination of the polypeptides of herpes simplex virus: types 1 and 2. PMID- 6243821 TI - The polyoma virus 100K large T-antigen is not required for the maintenance of transformation. PMID- 6243822 TI - Evidence that the src gene product of Rous sarcoma virus is membrane associated. PMID- 6243823 TI - The isolation of SV40 tsA/deletion, double mutants and the induction of host DNA synthesis. PMID- 6243824 TI - A new endonuclease restriction site which is at the locus of a temperature sensitive mutation in vaccinia virus is associated with true and pseudoreversion. PMID- 6243825 TI - Location of a new endonuclease restriction site associated with a temperature sensitive mutation of vaccinia virus. PMID- 6243826 TI - Characterization of an EBV-like virus from African green monkey lymphoblasts. PMID- 6243827 TI - Lysis of retroviruses with monoclonal antibodies against viral envelope proteins. PMID- 6243828 TI - Envelope properties of murine sarcoma virus-zero (MSV-Z). PMID- 6243829 TI - Attenuation of avian reticuloendotheliosis virus: loss of the defective transforming component during serial passage of oncogenic virus in fibroblasts. PMID- 6243830 TI - A cleavage product of the adenovirus DNA binding protein is active in DNA replication in vitro. PMID- 6243831 TI - Characterization of a subspecies of mouse interferon cross-reactive on human cells and antigenically related to human leukocyte interferon. PMID- 6243832 TI - Anticellular and antiviral effects of pppA(2'p5'A)n. PMID- 6243833 TI - [Results of combined treatment of small-cell bronchogenic carcinoma]. PMID- 6243834 TI - Some naive questions and thoughts on vitamin D and its relatives. PMID- 6243835 TI - Human papilloma virus infection of the uterine cervix. PMID- 6243836 TI - In vitro bioassay for human chorionic gonadotrophin. PMID- 6243837 TI - The occurrence of paracrystalline mitochondrial inclusions in normal human skeletal muscle. AB - Two different types of paracrystalline mitochondrial inclusions identical with or very similar to those already described in the literature for a variety of muscle diseases were found in human skeletal muscle biopsies obtained under general anesthesia before ischemia and after various periods of anoxia up to 150 min. As these crystalloids could be observed in seven of 14 healthy subjects and occurred in five of these seven cases either before or only 10 min after onset of ischemia, it is suggested that such mitochondrial inclusions develop not only under the influence of variant noxious stimuli, but may also represent a normal constituent of human skeletal muscle mitochondria. PMID- 6243838 TI - The occurrence of cytoplasmic lamellar bodies in normal and pathologic conditions. AB - Lamellar bodies are stacks of parallel cisternae of approximately regular spacing derived from ergastoplasm. Their occurrence was studied in various nervous and epithelial cells of different animal species in both normal and diseased subjects. This organelle appears to be, at least for some cell types, a normal cytoplasmic feature. The number of lamellar bodies increases in some pathologic conditions and when the cell metabolism is elevated. PMID- 6243839 TI - Nuclear inclusions in oculopharyngeal dystrophy. AB - The ultrastructural examination of skeletal muscle biopsies of three typical cases of autosomal dominant inherited oculopharyngeal muscular dystrophy showed collections of tubular filaments (8.5 nm in diameter) within muscle fibre nuclei. These filaments appear to be a characteristic morphological feature of oculopharyngeal dystrophy. PMID- 6243841 TI - Morphological demonstration of the first phase of polyomavirus replication in oligodendroglia cells of human brain in progressive multifocal leukoencephalopathy (PML). AB - Ultrastructural characteristics of adsorption, penetration and intracellular transport of polyomavirus is demonstrated in oligodendrocytes in PML. The findings are compared with those obtained by virological examinations of polyomavirus infections described in cell cultures. The morphology of the eclipse phase and the site of the beginning of virus assembly are also described. The vacuolization of the cytoplasm is considered to be the consequence of the production of viral protein and nucleic acid. The cytoplasmic virions surrounded by membrane in the early and late phases of replication are considered to be "infective virions", while those in the cytoplasm in a "free" state, aligned along membrane fragments or arranged in crystals are classified as "virus progenies". The first demonstration of polyoma virions between the separated lamellae of the myelin sheath of a viable axon is presented; their presence, however, is not considered to play a direct pathogenetic role in demyelination. PMID- 6243840 TI - Adrenomyeloneuropathy. A protracted, pseudosystematic variant of adrenoleukodystrophy. AB - Histopathological, immunocytochemical, and electron microscopical investigations were carried out in a man with a protracted history of spastic paraparesis, adrenal insufficiency and hypogonadism. Pathological findings were identical with those of the few previously reported cases of adrenomyeloneuropathy (AMN) including cytoplasmic lamellar inclusions consisting of two parallel 2.5 nm leaflets separated by a clear space of variable extent, in the brain, spinal roots, adrenal gland, and interstitial cells of the testis. No inclusions could be found in oligodendrocytes. In brain macrophages they are thought to represent breakdown products of pathological myelin stored in lysosomes, whereas in other localizations they might be an expression of the primary metabolic defect of the cell. Special attention was paid to the pseudosystematic type of fiber tract degeneration in the spinal cord. The dying-back pattern of axonal destruction was interpreted as a possible result of the multisegmental demyelination observed in these tracts. All known hormones could be localized in the pituitary by immunocytochemistry. Corticotrophs and gonadotrophs were numerous. The structural damage of the adrenal cortex and the interstitial cells of the testis is, therefore, considered to result from the inborn error of metabolism on the one hand and from an enhanced stimulation exerted by ACTH and gonadotrophins on the other. PMID- 6243842 TI - Topographic distribution pattern of Lafora-like bodies in the spinal cord of some animals. AB - The topographic distribution pattern and morphological features of Lafora-like bodies in the spinal cord of the dog, cat, fox, and baboon were examined by light and electron microscopy. The caudal lumbar and the coccygeal parts of the spinal cords were the predilection sites for the bodies in all animals and were very prominent in the ventral columns and intermediate substance. The bodies mainly composed of branching filaments were preferentially located in neuronal processes and rarely in astocytes. The histochemical characteristics of the bodies were identical in all animals and consisted mainly of polyglucosan. PMID- 6243843 TI - Neuropathy due to phytosol (agritox). Report of a case. AB - A case of intoxication with Phytosol (an insecticide) in a 29-year-old man is described. Ingestion of Phytosol (suicide attempt) produced signs of cholinergic crisis followed, after 16 days, by features of peripheral neuropathy and later, with the regression of signs of polyneuropathy, gradually increasing spastic paralegia. Electrophysiological investigation of nerves which were clinically moderately involved demonstrated sparing of sensory fibers and damage to motor fibers. There was no change in maximal motor conduction velocity. Histology of the clinically involved sural nerve revealed axonal changes together with demyelination, presumed to be secondary in type. This case shows that the susceptibility to delayed nervous system damage in man is greater than it might be expected from experimental studies and calls for caution in human exposure to these compounds. PMID- 6243844 TI - Hirano bodies in the axon of peripheral nerves in a case with progressive external ophthalmoplegia with multisystemic involvements. AB - Inclusions, ultrastructurally identical with Hirano bodies which were previously believed to be limited to the central nervous system (CNS), were found both within peripheral myelinated nerve axons and within terminal axons of neuromuscular junctions in the ocular muscles of an autopsied woman who had suffered from progressive external ophthalmoplegia with multisystemic involvements. Electron micrographs showed the inclusions to consist of beaded filaments or lattice-like structures with filamentous elements continuing onto neurofilaments in the axon. The corelation of these new pathological findings in peripheral nerve axons and ophthalmoplegia is discussed. PMID- 6243845 TI - Computed tomography of hepatocellular carcinoma. AB - Computed tomography (CT) was used to evaluate 16 cases of hepatocellular carcinoma. CT identified and localized the tumor in 15 cases, an overall detection rate of 94%. The technique of dynamic CT scanning (rapid sequential scans after intravenous bolus of contrast medium), used in several cases, proved useful for determining patency of the portal vein and inferior vena cava and for demonstrating arteriovenous shunting due to tumor. CT detected some tumors missed by radionuclide scanning and arteriography. An approach to the diagnostic workup of patients with known or suspected hepatoma is presented, with a discussion of the roles of ultrasonography, radionuclide scanning, and arteriography. PMID- 6243847 TI - Gray scale ultrasound of the parotid gland. AB - Gray scale ultrasonography permits markedly improved visualization of the parotid gland compared with bistable methods. The normal parotid is echogenic, similar in echo generation to thyroid tissue, but flatter anatomically. Ultrasound can detect a mass lesion in the area of the parotid gland and define whether it is intrinsic or extrinsic, but as yet has limited usefulness in determining the specificity of an abnormality. PMID- 6243846 TI - Computed tomography in the diagnosis of cavernous hemangioma of the liver. AB - Computed tomography (CT), using a sequential timed scanning technique, was performed on six patients with hepatic cavernous hemangiomas. Initial examination shows a moderately homogeneous circumscribed area with reduced attenuation values. Serial scans after injection of a bolus of contrast material show early peripheral opacification while the central part of the lesion retains low attenuation values for several minutes. Later scans demonstrate a variable degree of "filling in" of the central part of the hemangioma. If the characteristic appearance of this lesion is recognized, confusion with other ominous lesions and biopsy can be avoided. Because of limited experience, the described pattern may not be absolutely pathognomonic for hemangioma, so angiography is currently advised to confirm the diagnosis. PMID- 6243848 TI - Acute emphysematous cholecystitis: an ultrasonic diagnosis. PMID- 6243849 TI - Analgesic polypeptides: the endorphins. PMID- 6243850 TI - Coronaviruses in Balkan nephritis. PMID- 6243851 TI - Pindolol in the treatment of hypertension: systolic time intervals as a predictor of response to beta receptor blockade. PMID- 6243852 TI - Manifestation of iron deficiency at various levels of dietary iron intake. AB - The purpose of this study was to determine the interrelationships between iron stores, serum iron, hemoglobin, myoglobin, and cytochrome c under conditions of iron deficiency that did not interfere with normal growth. Rats were given diets containing from 7 to 500 mg iron per kilogram of diet during a period of 3 weeks of rapid growth between weaning at 21 days and approaching sexual maturity at 42 days. We found that the level of iron intake required for a maximum concentration of hemoglobin was similar to that which results in a maximum level of tissue cytochrome c. The severity of iron deficiency anemia was proportionally similar to the degree of depletion of muscle cytochrome c at all levels of iron intake below 25 mg/kg diet. The results indicate that even the mildest degree of nutritional iron deficiency anemia also affected tissue cytochrome c and could impair cytochrome-dependent mitochondrial function. PMID- 6243853 TI - Causes of death and metastatic patterns in patients with mammary cancer. Ten-year autopsy study. AB - As periodic evaluation of the causes of death in cancer patients may provide guidelines for further research on supportive care in cancer, the authors studied autopsy records of 144 mammary-cancer patients from the past ten years. The causes of death were analyzed and compared for the first and second five-year periods. During the first five-year period (65 cases), death was caused by the malignant process itself in 70.8% of the patients, by infection in 10.8% and by hemorrhage in 7.7%. During the second five-year period (79 cases), the malignant process itself was still the most frequent cause of death but in only 47.4% of the patients, and deaths due to infections (23.7%) and hemorrhages (9.2%) were relatively more frequent, without noticeable changes in the patients' survival times. These findings may be related to the more aggressive methods of treatment applied in recent years. The metastases to the organs tended to be massive, and except for the lymph nodes, the lung was the organ most frequently involved by tumors (60%), followed by bone (54%), liver (54%), adrenal gland (36%), pleura (36%) and brain (26%). As the chance of life-threatening infections is great in mammary cancer, the early detection and treatment of infections in mammary-cancer patients could become an important factor in prolonging the survival of these patients. PMID- 6243854 TI - Inflammatory malignant fibrous histiocytoma. AB - This report describes a 13-year-old girl with inflammatory malignant fibrous histiocytoma of the abdomen. Clinical, pathologic, and ultrastructural features of this subgroup of tumors are discussed. Differential diagnostic criteria are reviewed. PMID- 6243855 TI - An outbreak of adenovirus type 3 disease at a private recreation center swimming pool. AB - In the period June 6--July 24, 1977, and outbreak of illness due to adenovirus type 3 (AV3) occurred in residents of a suburban community (Community A), Dekalb County, Georgia. Based on surveys, at least 105 cases occurred. The illness was primarily characterized by sore throat, fever, headache, and anorexia. Conjunctivitis affected only 34 of 105 (32%) of the individuals in two surveys. Frequent use of a private swimming pool was associated with illness in Community A residents. The outbreak coincided with a temporary defect in the pool filtration system which probably prevented maintenance of proper chlorine levels in the pool water, and suggested that the infection was spread by pool water. However, the predominant mode of transmission could not be shown conclusively to be waterborn rather than person-to-person. PMID- 6243856 TI - Endogenous opioid systems in brain. PMID- 6243857 TI - A defect in platelet aggregation in Bartter's syndrome. AB - A defect in both the first and second phase of platelet aggregation was found in four subjects with Bartter's syndrome, although template bleeding times were normal. The platelet abnormality was exacerbated by restriction of dietary sodium and lessened by the administration of inhibitors of prostaglandin synthesis. The aggregation defect was not found in other hypokalemic patients or in sodium restricted normal control subjects. Platelet rich plasma from the subjects with Bartter's syndrome had an abnormally high content of cyclic adenosine 5' monophosphate (AMP), which may have been responsible for the disordered platelet function. Plasma of these subjects induced both the high content of cyclic AMP and the aggregation defect in normal platelets, whereas suspension of the subjects' platelets in normal plasma improved their aggregation. These findings describe a unique defect of platelet aggregation in Bartter's syndrome, which may be associated with the altered prostaglandin metabolism found in this condition. PMID- 6243858 TI - Herpes zoster and small cell bronchogenic carcinoma. AB - In nine of 74 (12 per cent) consecutive, previously untreated patients with small cell bronchogenic carcinoma receiving combination chemotherapy herpes zoster developed. This is the highest frequenzy reported for this viral infection in patients with nonlymphoproliferative solid tumors. Cutaneous dissemination developed in six of the nine patients, but visceral involvement did not occur. The major difference between the patients with herpes zoster and those without was the superior duration of median survival for the infected patients. No relationship could be established between the development of herpes zoster and the extent of neoplastic disease, prior radiotherapy, treatment with specific chemotherapeutic agents or corticosteroids, cutaneous anergy or granulocytopenia. Serum specimens obtained from six of the nine patients prior to their infection demonstrated the preexistence of varicella zoster antibodies. As more effective and intensive chemotherapy prolongs the survival of patients with solid tumors, it is possible that the frequency of herpes zoster infection may approach that observed in patients with lymphoproliferative malignancies. PMID- 6243859 TI - Coxsackie B5 heart disease. Demonstration of inferolateral wall myocardial necrosis. AB - A case of Coxsackie B5 viral myopericarditis is presented in which the diagnosis of inferolateral wall myocardial necrosis was made on the basis of specific cardiac enzyme changes and radionuclide myocardial imaging. This localized damage may have resulted from coronary arteritis with resulting infarction or necrosis secondary to preferential viral involvement of the inferolateral wall of the myocardium. Hepatitis and cerebral embolism complicated the case, with the latter suggesting endocardial disease. PMID- 6243860 TI - Nephrotic syndrome associated with adenocarcinoma of the breast. AB - Although the nephrotic syndrome has been reported in association with a wide variety of neoplastic diseases, it has only rarely been noted as a complication of breast carcinoma. We describe a patient who presented with the nephrotic syndrome and who was subsequently found to have carcinoma of the breast. The findings on renal biopsy were indicative of membranous nephropathy with positive immunofluorescent staining for immunoglobulin G (IgG) and the third component of complement (C3). The nephrotic syndrome completely resolved following successful treatment of the cancer. We have now followed this patient for over two years and there has been no recurrence of tumor or the nephrotic syndrome. PMID- 6243861 TI - Suppression by progesterone of nonspecific in vitro lymphocyte stimulation in mice as a mechanism for the enhancement of herpes simplex virus type 2 vaginal infection. AB - The role of antibody, interferon, and cell-mediated immunity (CMI) were studied to determine the mechanisms for progesterone enhancement of vaginal herpes simplex virus type 2 (HSV 2) infection in mice. Three groups of mice were studied: nonpregnant control, pregnant, and nonpregnant progesterone-treated mice. Vaginal infection with HSV 2 did not elicit a neutralizing antibody or a systemic interferon response in any of the groups tested. Splenic lymphocytes from noninfected and infected mice were stimulated in vitro with a nonspecific T cell mitogen concanavalin (Con A) to measure the proliferative phase of CMI in these groups of mice. No suppression of (3H) thymidine (3HTdR) uptake was found in the pregnant or nonpregnant, progesterone-treated animals as compared to nonpregnant control mice. When progesterone was added directly to the splenic lymphocytes and continuously present during Con A stimulation a statistically significant depression of 3HTdR incorporation was found. We concluded that progesterone depresses Con A stimulation of murine lymphocytes, but progesterone must be continuously present to do so. PMID- 6243862 TI - Comparative study of high-dose chorionic gonadotropin on the human and rat corpus luteum and effect of gonadotropin-releasing hormone on human luteal function. AB - Human chorionic gonadotropin (hCG) was administered to pseudopregnant rats with 4 day-old corpora lutea and to normal women on days 16 to 18 following onset of menses. In the rat serum progesterone levels fell by 90% within 8 hours as did unoccupied luteal luteinizing hormone (LH) receptors following treatment with hCG (100 IU). Total receptor number for LH, however, remained unchanged until after 12 hours. In the woman 20,000 or 40,000 IU of hCG given on day 16 and day 18 of the cycle did not reduce serum progesterone or serum estradiol levels although the serum hCG level was similar to that achieved in the rat. In fact, serum progesterone levels rose and the cycle length was extended by hCG treatment in the human. Conversely, treatment of the woman with gonadotropin-releasing hormone (GnRH, 500 microgram on day 16 and on day 18) caused an initial rapid rise, then a fall in serum progesterone levels and the cycle length was shortened. It was concluded that the human corpus luteum may be resistant to densensitization by hCG but possibly not to LH. However, the possibility cannot be excluded that GnRH may compromise luteal function through mechanisms independent of effects on pituitary gonadotropin secretion or action. PMID- 6243863 TI - Evidence that danazol inhibits gonadotropin-induced ovarian steroidogenesis at a point distal to gonadotropin-receptor interaction and adenosine 3',5' cyclic monophosphate formation. AB - The action of danazol on 125I-human chorionic gonadotropin (hCG) binding, gonadotropin-stimulated adenosine 3',5' cyclic monophosphate (cAMP) accumulation and progesterone production has been investigated in luteinized rat ovaries. Preincubation of luteal cells for short periods of time with increasing concentrations of danazol caused a significant inhibition of gonadotropin stimulated steroidogenesis. The inhibitory effect of danazol was both concentration and time dependent. Danazol also reduced progesterone production in response to cholera enterotoxin and 8 bromo-adenosine-cAMP, but it had no effect on hCG, luteinizing hormone, and cholera enterotoxin stimulated cAMP formation. Similarly danazol did not affect 125I-hCG binding as assessed by the equilibrium dissociation constant (Kd) and number of hormone-binding sites on the luteal cell surface. These results suggest that in intact luteal cells danazol inhibits steroidogenesis at a point distal to hormone-receptor interaction and cAMP formation. PMID- 6243864 TI - Clinical importance of the diagnosis of trophoblastic pseudotumors. AB - Trophoblastic pseudotumor, a type of gestational trophoblastic neoplasia, is discussed in the context of a case report. The criteria for diagnosis, lack of placental villi, cytotrophoblast, extensive hemorrhage, and necrosis, can only be fulfilled on histopathologic study of a hysterectomy specimen. Clinical management should be based on the titer of the beta subunit of human chorionic gonadotropin, not on the type of gestational trophoblastic neoplasia. PMID- 6243865 TI - Uveitis associated with sarcoidosis and angiotensin converting enzyme. AB - We evaluated serum angiotensin converting enzyme activity in three groups of patients as follows: 20 patients with systemic sarcoidosis and ophthalmic manifestations of the disease (Group 1); 27 patients with granulomatous uveitis and no evidence of systemic sarcoidosis (Group 2); and 17 patients with well defined uveitis syndromes, both granulomatous and nongranulomatous (Group 3). Serum angiotensin converting enzyme activity in control subjects was 22.0 +/- 0.7 nanomol/min/ml (mean +/- S.E.). Compared to control subjects, serum angiotensin converting enzyme activity was significantly increased in Groups 1 and 2 for patients not using corticosteroids (57.9 +/- 7.4 and 41.5 +/- 4.4 nanomal/min/ml, respectively) as well as those using corticosteroids (40.3 +/- 5.1 and 35.6 +/- 4.8 nanomal/min/ml). Enzyme activity was not significantly different from controls for Group 3. Our study shows that the increase of serum angiotensin converting enzyme activity in some patients with granulomatous uveitis is strong evidence of sarcoid uveitis even in the absence of clinicoradiographic or histologic findings of systemic sarcoidosis. PMID- 6243866 TI - Varicella dendritic keratitis. AB - A 7-year-old boy and a 3-year-old girl suffered from unilateral disciform keratitis and iritis associated with varicella. While they were treated with topical corticosteroid, idoxuridine, and atropine drops, dendritic lesions typical of herpes zoster appeared four months after the onset of eruptive skin lesions. Using the direct immunofluorescent method, we showed varicella-zoster virus antigen in the epithelial cells scraped from the dendritic lesion. PMID- 6243867 TI - Hepatoma metastatic to the orbit. AB - A 69-year-old man with a history of cirrhosis of the liver had unilateral progressive proptosis without jaundice, abdominal pain, or gastrointestinal symptoms. Results of laboratory and radiographic studies were also normal. Orbital biopsy revealed hepatocellular carcinoma. Although hepatocellular carcinoma has often been shown to metastasize to the brain and often to the flat bones of the skull, to the best of our knowledge, this is the first histologically proven case of hepatoma metastatic to the orbit. PMID- 6243868 TI - Malignant gliomas of the optic nerve pathways. AB - We compared the clinical course and histopathologic findings in five patients with malignant gliomas originating from the optic nerve pathways with those in previously reported cases to elucidate further the clinical features of this tumor and facilitate future diagnoses. Patients with malignant optic nerve pathway gliomas had unilateral or bilateral visual dysfunction, which was often accompanied by periorbital discomfort in an otherwise asymptomatic adult. Regardless of origin, the clinical course invariably was bilateral blindness rapidly followed by death. Occasionally, the diagnosis was made preoperatively and was confirmed by surgical exploration and biopsy. PMID- 6243869 TI - The relationship of terminal duct hyperplasia to mammary carcinoma in 7,12 dimethylbenz(alpha)anthracene-treated LEW/Mai rats. AB - The evolution of dysplasias and carcinomas in the inguinal mammary glands of LEW/Mai rats given 7,12-dimethylbenz(alpha)anthracene (DMBA) by gastric gavage was studied with the use of stained whole mounts. Two major dysplasias, hyperplastic terminal end buds (HEBs) and hyperplastic alveolar nodules (HANs), developed prior to mammary carcinomas. HEBs were present in the mammary glands of approximately 70% of the rats within 1 week following DMBA. The percentage of rats with these lesions and the incidence of HEBs in the mammary gland decreased prior to the appearance of palpable and microscopic tumors. During the time when tumors first became evident (40-80 days), the percentage of rats with HEBs (11%) paralleled the percentage of rats with mammary tumors (12%). The initial percentage of rats with HEBs ( approximately 70%) paralleled the final tumor incidence (71%) observed in DMBA-treated rats that were allowed to live until they developed tumors. The histologic features of HEBs resembled those of the carcinomas, and HEBs were present in the immediate vicinity of some of the microscopic and palpable tumors. With only one exception, the location of microscopic tumors in the mammary gland was consistent with their derivation from small terminal ducts. These data are compatible with a developmental relationship between HEBs and mammary carcinoma. HANs, on the other hand, developed relatively late (ie, 30 days) following DMBA administration and became more numerous with the passage of time. Over the period of time when mammary carcinomas first became evident, the percentage of rats with HANs (73%) was inconsistent with a developmental relationship between HANs and mammary carcinoma. This conclusion was supported by the absence of HANs in the vicinity of microscopic tumors, by the dissimilarity between the histologic features of HANs and mammary carcinomas, and by their absence from the mammary gland during the time when at least some of the mammary tumors must have arisen. The results implicate terminal duct hyperplasia in the histopathogenesis of rat mammary carcinomas. PMID- 6243870 TI - The relationship between cytotoxicity and prognostically significant histologic changes in lymph nodes from patients with cancer of the breast. AB - Axillary lymph nodes obtained from 37 patients with cancer of the breast were used in a microcytotoxicity assay against a human mammary cancer cell line, ALAB. Cell suspensions made from 60 individual lymph nodes and 51 lymph node pools were tested. Each lymph node was graded for the extent of the histologic changes of sinus histiocytosis (SH), paracortical hyperplasia (PCH), and germinal center hyperplasia (GCH). High levels of cytotoxicity correlated significantly with the presence of SH and PCH. When multiple lymph nodes of individual patients were pooled and tested, a high intensity of GCH correlated with a low degree of cytototoxicity. The cytotoxic activity of pooled lymph nodes from different axillary regions was studied in 20 patients. In 7 of these patients, low axillary lymph node cells were more cytotoxic than high axillary node cells. The reverse was found for 7 patients, and there was no difference in cytotoxicity between axillary regions in 6. Cytotoxic lymph node pools had high SH and low GCH whether they were obtained from the low or high region. Noncytotoxic lymph node pools from the high axillary region had a low intensity of all three histologic reactions. In contrast, noncytotoxic lymph node pools from the low axillary regions had high intensities of SH, PCH, and GCH. These results suggest that germinal center hyperplasia in the lymph nodes nearest an advancing tumor is associated with a local suppression of cytotoxic cell activity. PMID- 6243871 TI - Enzyme patterns in human hepatocellular carcinoma. AB - Characteristic enzyme alterations have been demonstrated during the stages of experimental hepatocarcinogenesis in rats. The activity of gamma-glutamyl transpeptidase (GGTPase) in hyperplastic and neoplastic hepatocytes is usually increased, whereas that of canalicular adenosine triphosphatase (ATPase) and of glucose-6-phosphatase (G6Pase) is more variable. The activities of these marker enzymes were studied by histochemical techniques in 10 human hepatocellular carcinomas (HCCs), 1 liver cell adenoma, and 1 cholangiocarcinoma of liver. In 9 cases, the nontumorous liver was also examined. All HCCs, but not the liver cell adenoma, displayed enzyme patterns that differed from normal. GGTPase activity was markedly increased in 8 HCCs, whereas the activities of G6Pase and ATPase were lost in 6 and 8 HCCs, respectively. These enzyme alterations occurred as 5 of 7 possible combinations, resulting in significant heterogeneity of enzyme phenotypes, similar to that in experimental hepatocarcinogenesis. PMID- 6243873 TI - [3H]ouabain binding during the monolayer organization and cell cycle in MDCK cells. AB - The specific binding of [3H]ouabain in an epithelial cell line derived from a dog kidney (MDCK) was determined during epithelial reorganization and also during the cell cycle. In suspended cells, the specific binding of [3H]ouabain is reduced 67% compared with the binding obtained in a complete monolayer. After plating back these cells on a permeable support, both transepithelial electrical resistance and [3H]ouabain binding increase with time of incubation. [3H]ouabain binding decreases during S and G2 phases of the cell cycle to reach a minimum during mitosis and increases again during GI. The transepithelial electrical resistance, determined simultaneously, shows the same behavior. The reduction in the number of [3H]ouabain binding sites in two different circumstances in which the epithelial membrane organization is disrupted and the increase in [3H]ouabain binding sites when the epithelial membrane is reorganized are consistent with the hypothesis that the number of pumping sites responsible for the active step in the transepithelial active transport is additional to the number required to maintain the intracellular ionic composition. PMID- 6243872 TI - Alterations in responses to bradykinin, angiotensin I, and angiotensin II during the induction phase of one-kidney, one-wrapped hypertension and associated arterial disease in rabbits. AB - During the induction phase of low-renin, one-kidney, one-wrapped hypertension in rabbits,serum angiotensin converting enzyme (ACE) activity is depressed and correlates inversely with the degree of necrotic arterial disease that develops. Responses to the vasoactive polypeptides, bradykinin (BK), angiotensin I (AI), angiotensin II (AII), the ACE blocker teprotide, and the AII antagonist 1-sar-8 ile AII were studied. Responses to BK, AII, and AI showed significant changes in both magnitude and duration (recovery time). Recovery time for depressor responses to BK in hypertensive rabbits was approximately three times that in the control period. One-wrapped, two-kidney control rabbits without hypertension associated arterial disease showed no change in BK recovery time, although serum ACE activity was significantly depressed. In the experimental period BK recovery time correlated directly with the degree of arterial disease and indirectly with the final serum ACE activity. Duration of the pressor responses after AII correlated directly with the degree of arterial disease and indirectly with final serum ACE activity. In untreated hypertensive rabbits the percentage of increases in blood pressure after AI relative to control animals were decreased, and for all hypertensive rabbits' the increase in blood pressure correlated directly with the final serum ACE activity. Long-term treatment with teprotide moderated the hypertension but had little effect on serum ACE activity or the responses to BK, AII, and AI. Short-term infusions of 1-sar-8-ile AII and teprotide caused significant decreases in blood pressure in both the control and experimental periods, although no change in response to either polypeptide occurred. These studies support other evidence that pressor components of the renin-angiotensin system do not sustain the elevation of blood pressure in this form of experimental hypertension. Alterations in response patterns following AII and AI suggest that a vasodepressor system may be altered. In addition, part of the altered response to BK, and possibly AII, appears related to the development of the hypertension-associated arterial disease. PMID- 6243874 TI - Mechanisms involved in alpha-adrenergic phenomena: role of calcium ions in actions of catecholamines in liver and other tissues. AB - Epinephrine and norepinephrine binding sites with the physiological characteristics of alpha-adrenergic receptors have been identified in the plasma membranes of liver and other cells. Interaction of catecholamines with these receptors causes a mobilization of calcium ions from mitochondria and perhaps other intracellular stores in liver cells. In other cells, there may also be influx of extracellular calcium ions. Evidence is presented in support of the hypothesis that the rise in cytosolic calcium ions resulting from these changes is responsible for many of the alpha-adrenergic actions of catecholamines. Possible mechanisms by which activation of alpha-adrenergic receptors causes changes in calcium and other aspects of cellular metabolism are discussed. PMID- 6243875 TI - [3H]ouabain binding and Na+-K+-ATPase activity in human placenta. PMID- 6243876 TI - Studies of renal cell function using cell culture techniques. AB - Cell culture, a powerful tool for the study of cell biology, offers advantages for the study of renal cell function. Epithelial cells derived from a variety of organs, including the kidney, form oriented epithelial sheets in culture that have many structural characteristics (microvilli, tight junctions) of epithelia in situ. There is evidence of transepithelial transport of salt and water by cells of two lines (MDCK and LLC-PK1) derived from mammalian kidney. LLC-PK1 cells may also manifest the glucose transport system of the proximal tubule. Cells of both lines have adenylate cyclase activity sensitive to hormones. Two lines of cells derived from toad urinary bladder form epithelia with a high transepithelial resistance and transport sodium actively from apical to basolateral surface. The rate of sodium transport in both lines is stimulated by cyclic AMP and by aldosterone. There are important differences in the characteristics of the response of the two lines to aldosterone as well as in their sensitivity to inhibition of sodium transport by amiloride. These differences may lead to new insights regarding the molecular events in the response to aldosterone and in the inhibitory action of amiloride. Cultures of kidney cells have also been used effectively to study the biosynthesis of the hormonal derivative of vitamin D and to study prostaglandin production. In addition, cell culture is ideally suited for study of the developmental biology of the kidney. PMID- 6243877 TI - Analysis of sympathetic discharges during cardiogenic hypertensive chemoreflex. AB - Serotonin activates a cardiogenic hypertensive chemoreflex. During this reflex, sympathetic efferent neural discharges were examined in 10 anesthetized dogs. Thoracic nerves were identified, severed distally, and placed across electrodes. The efferent neurogram was recorded along with an electrocardiogram and blood pressure and stored on tape. Neurograms were later analyzed by a Lab 8/e computer with a Schmitt trigger. The resting tone and the elicited discharges of the multifiber preparations were plotted as poststimulus histograms. The integrals of the histograms were normalized. During the reflex, sympathetic efferent discharges averaged 4.9 (+/- 0.8) s in duration and the total discharge frequency was 199 (+/- 16)% of control tone. The evoked peak blood pressure response averaged 221/171 mmHg. Following autonomic blockade, the attenuated blood pressure response averaged 125/96 mmHg. The sympathetic efferent discharges then lasted 5.2 (+/- 0.7) s (NS). However, total discharge frequency (268 +/- 37% of control tone) was significantly greater (P less than 0.01) that before autonomic blockade. These data suggest that baroreceptors influence the rate of discharge and the total amount of neural traffic, but not the duration of the sympathetic response evoked by the cardiogenic hypertensive chemoreflex. PMID- 6243878 TI - Probability of peripheral interaction between motor units and implications for motor control. AB - Potential and importance of mechanical interactions between motor units are examined. Studies were conducted on simple physical models of systems of motor units assembled from separate muscles and driven with electrical stimulus. Two separate muscles were connected to move a common load to represent mechanically coupled motor units while avoiding other interactions present between natural units. Force, velocity, length, power, and work outputs of one unit were measured with and without stimulus to the other unit. Excitation of one unit modified all response measures in the other. The basis for these interactions appears equally applicable to real motor units. Consequently, unqualified use of such terms, which imply independence, as quantal, summation, and average unit response is not acceptable without qualification when referring to activity of motor units. It is argued that the effects of force-velicty and length-tension relationships will cause appreciable mechanical interaction between motor units. Therefore, central nervous system strategies for organization of motor control cannot depend on unchanging response of individual units, and the principle of superposition should not be assumed in analyses of motor activities. The nature of the interactions suggests that the total effect of a unit response may include a "negative force" phase, and also energy exchanges can be expected between motor units in some configurations. PMID- 6243879 TI - Distribution of vagal cardioinhibitory neurons in the medulla of the cat. AB - Experiments were done in cats anesthetized with chloralose, paralyzed and artificially ventilated cats to obtain electrophysiological evidence on the medullary site of origin of vagal cardioinhibitory fibers. The regions of the nucleus ambiguus (AMB), dorsal motor nucleus of the vagus (DMV), nucleus tractus solitarius (NTS), and external cuneate nucleus (ECN) were systematically explored for units responding both to antidromic stimulation of the cardiac branches of the vagus (CBV) and to orthodromic stimulation of the carotid sinus and aortic depressor nerves. Eighty-six single units conforming to these criteria were found in the medulla: 30 in the AMB, 26 in the DMV, 12 in the NTS, 8 in the NTS-DMV border region, and 10 in the ECN. Antidromically evoked spikes had durations of 0.5--2.5 ms and followed stimulation frequencies of 20--500 Hz. The axons of these units conducted at velocities of 3.3--20.8 m/s. The specificity of activation of medullary units by cardioinhibitory fibers was tested in 11 units, which were found to respond consistently with an antidromic spike to stimulation of CBV but not to stimulation of the thoracic vagus. In eight spinal animals low threshold (less than 15 microA) sites eliciting vagal bradycardia were found in the same medullary nuclei where cardioinhibitory units had been located. These results indicate that vagal cardioinhibitory axons, originate in at least three medullary nuclei, the AMB, DMV, and NTS. Unit activity from the ECN may have been recorded from carioinhibitory fibers because of the short duration of the spike potentials. PMID- 6243880 TI - Pancreatic islet autotransplantation: results in dogs with chronic duct ligation. AB - The influence of pancreatic acinar cell atrophy and fibrosis on islet tissue autotransplantation was studied in dogs. Thirty-nine dogs underwent pancreatic duct ligation. After 6 weeks marked acinar cell atrophy and fibrosis developed, similar to that in human chronic pancreatitis. Intravenous glucose tolerance testing revealed only a minor decrease in K value (percent/min decline in plasma glucose) from 2.9 +/- 0.2 to 2.4 +/- 0.1 during the 6 weeks. In a control group of normal dogs, 23 of 26 transplants were successful. In a group of 12 duct ligated dogs, only 1 of 12 transplants was successful with identical techniques (p less than 0.001). Variations in technique to increase or decrease tissue dispersal did not improve the results in other groups (two successes in 27 dogs). New techniques are required if pancreatic islet transplantation is to be consistently effective in the presence of chronic inflammatory disease of the pancreas. PMID- 6243881 TI - Management of tumors of the liver. Combined use of arteriography and venography in the assessment of resectability, especially in hilar tumors. AB - Twenty-five primary and secondary malignant tumors involving the liver were assessed preoperatively by combined hepatic arteriography and portal venography. The resectability of the lesions as judged by these radiographic techniques was compared with the operative findings. Only 1 of 6 peripheral nonhilar tumors was unresectable, in contrast to 11 of 19 tumors involving the hilus In every case the operative findings confirmed the preoperative radiologic data. Of the patients with hilar lesions, four had isolated unilateral involvement of either the main trunk or a major secondary branch of the lobar artery and vein and were all resectable. None of the 11 hilar lesions with bilateral or stem involvement of the vasculature were resectable. It is suggested that hepatic angiography not only yields information on diagnosis, anatomic abnormalities and concurrent disease, but also is important in assessing tumor resectability. For this purpose, both selective hepatic arteriography and splenic venography are necessary. PMID- 6243882 TI - Ultrastructural study of stroma in human mammary carcinoma. AB - This investigation was designed to study the origin of the stromal component of human mammary carcinoma. Tissues from 30 proved breast carcinomas were studied. Under a light microscope with special stains, an increased connective tissue component was seen in carcinoma. Gluteraldehyde-fixed tissue was examined under an electron microscope. The stroma appeared to be composed of fibroblastic, myofibroblastic, histiocytic and primitive mesenchymal cells. Elastic fibers were intimately intermingled with collagen and reticulin and seen in close association with carcinoma cells. In some areas they were seen inside the carcinoma cells with discontinuous cytoplasmic membrane, as if they were formed by the cancer cells. This observation suggests that breast carcinoma cells play an important role in the production of elastic fibers in association with stromal cells and also stimulate the proliferation of the stromal cellular component. PMID- 6243883 TI - Problems and pitfalls in acetaldehyde determinations. AB - The determination of acetaldehyde in biologic samples is complicated by a variety of formation and disappearance reactions occurring in the present methods of acetaldehyde analyses. The acetaldehyde formation (ethanol oxidation) in deproteinized supernatant of tissue preparations is prevented by the use of thiourea. During deproteinization, however, it is not inhibited by thiourea, and this remains the main problem in blood acetaldehyde determinations. To circumvent this problem, the use of a correction curve is proposed which is generated by adding control blood samples to the deproteinizing agent such that the blood dilution, temperature, and the ethanol concentrations (the main factors affecting the artifactual acetaldehyde formation) in the controls are identical to those of the samples. Disappearance reactions mainly include loss of acetaldehyde due to binding and/or metabolism. The problem seems to be pronounced with human blood samples, and it is recommended that they be rapidly ( less than 5 sec) deproteinized. PMID- 6243884 TI - Standardized device for the assay of oxygen consumption adaptable to commercial photometers. PMID- 6243886 TI - Carbohydrate interference in assays based on the periodate-coupled thiobarbituric acid reagent. PMID- 6243885 TI - The synthesis of 4-methylumbelliferyl alpha-ketoside of N-acetylneuraminic acid and its use in a fluorometric assay for neuraminidase. PMID- 6243887 TI - Solubilization of pulmonary angiotensin-converting enzyme with 1-O-n-octyl-beta-D glucopyranoside. PMID- 6243888 TI - Stabilization of proteins immobilized on Sepharose from leakage by glutaraldehyde crosslinking. PMID- 6243889 TI - Use of soluble, collagenous peptides from medium of chick calvaria cultures as substrate for prolyl hydroxylase. PMID- 6243890 TI - Rod-shaped bodies and crystalloid inclusions in ocular vascular endothelia of adult and developing Macaca mulatta. AB - In addition to the usual organelles, endothelial cells of ocular blood vessels and Schlemm's canal in adult and fetal Macaca mulatta, contain two types of inclusions: rod-shaped bodies and crystalloids. The rod-shaped bodies are similar to those first described in arterial endothelia of the rat. They are between 0.2 to 0.35 micrometer in diameter, up to 2.5 micrometers in length, and are membrane bounded. The crystalloid inclusions are up to 1.2 micrometers in diameter and are associated with the granular endoplasmic reticulum. Their crystalline lattice consists of subunits, 28 nm in diameter, which are either arranged in rows separated by amorphous matrix or tightly packed in a honeycomb-like lattice. The rod-shaped bodies are much more numerous than the crystalloids; however, both kinds of inclusions are consistently found in both adult and fetal vessels. The represent normal components of ocular vascular endothelia which appear very early in the development of the eye. PMID- 6243891 TI - The heterogeneity of hepatocytes during the postnatal development of the mouse. AB - Development of the hepatocyte heterogeneity was studied histochemically during the postnatal period. At birth ornithine carbamoyltransferase (OCT). succinate dehydrogenase (SDH) and NADH dehydrogenase (NADHDH) activities were evenly distributed throughout the liver acinus. Slightly uneven distribution within the acinus appeared at 3 days after birth in SDH and at 4 days after birth in OCT and NADHDH, changing to that of adult type at 10 or 12 days after birth which is characterized by a marked difference in the activities between zone 1 and 3. However, in animals of all age groups studied, glycogen was decreased mainly in zone 1 and 2 after 6 or 10 h of fasting and glucose 6-phosphatase activity was markedly reduced or disappeared in zone 3 and often in zone 2 after carbon tetrachloride administration. The results show that so-called "functional and structural heterogeneity among hepatocytes" consists of at least two different components, that formed gradually during the postnatal development and that existing already at birth. PMID- 6243892 TI - Pathophysiology of nerve conduction: relation to diabetic neuropathy. AB - Pathophysiologic and clinicopathologic aspects of diabetic nerve disease are reviewed. Abnormal modes of impulse conduction in diseased nerves include decreased conduction velocity, temporal dispersion of impulses, frequency-related and total conduction block, abnormal cross-talk, and impulse reflection. Because structural and electrophysiologic variables (such as fiber geometry, ionic channel density, and properties of the extracellular milieu) vary with diameter, it is suggested that pathophysiologic mechanisms also should vary with diameter. Topographic patterns of clinical deficit, and their pathologic basis, are reviewed; it is suggested that lesions distributed at random along the length of the entire fiber may result in dysfunction that exhibits distinct proximal-distal gradients. PMID- 6243893 TI - Pathology of autonomic neuropathy in diabetes mellitus. AB - Pathologic changes in the autonomic nervous system were studied postmortem in five cases of insulin-dependent diabetes of early onset. All had had clinical evidence of peripheral sensorimotor neuropathy and developed disturbances of autonomic function that included postural hypotension, diarrhoea, bladder dysfunction, impotence (in the men), and signs of cardiac denervation. In coeliac and other sympathetic ganglia there were many distended ('giant') or vacuolated neurons as well as enlarged club-shaped neural processes. The vagus nerve and sympathetic trunks showed severe loss of myelinated fibres. Smooth muscle in many viscera showed a hitherto undescribed focal hyaline degeneration. There were inflammatory changes in the autonomic ganglia in all cases and in or around bundles of unmyelinated nerve fibres in many. These findings suggest that there may be several different pathogenetic mechanisms involved in the development of autonomic neuropathy in diabetes. PMID- 6243894 TI - Physiology of the urinary bladder and urethra. AB - Activation of the parasympathetic pathways to the detrusor muscle and inhibition of somatic input to the external urethral sphincter are the essential neuronal events initiating release of urine. The former occurs via a spinobulbospinal pathway, whereas the latter is produced by inhibitory mechanisms in the sacral spinal cord. The sympathetic outflow to the urinary tract promotes urine storage by increasing urethral resistance and depressing detrusor contractions. Sympathetic activity is generated at least in part by a spinal vesicosympathetic reflex pathway. Evidence indicates that the integration of sympathetic and parasympathetic inputs to the bladder can occur at the level of the peripheral autonomic ganglion as well as at levels of the effector organ. The existence of facilitatory and adrenergic inhibitory mechanisms in ganglia and the identification of spontaneously active ganglion cells raise the possibility that vesical ganglia may have a role in modulating or "filtering" the efferent neural input to the bladder. PMID- 6243895 TI - Serum angiotensin-converting enzyme activity in evaluating the clinical course of sarcoidosis. AB - Thirty-five patients with sarcoidosis were serially monitored for serum angiotensin-converting enzyme activity by a simple radiochemical assay, and we analyzed the relation of such activity to the clinical status as judged from changes in chest roentgenograms, pulmonary function, or symptoms. Converting enzyme levels closely paralleled and occasionally antedated changes in clinical status in patients either undergoing spontaneous remission or being treated with prednisone. Converting enzyme activity seems to be a sensitive index for evaluating the clinical course of sarcoidosis. Converting enzyme determinations may be helpful in corroborating the diagnosis, assessing the likelihood of spontaneous remission, confirming the clinical status of the patient, and determining the adequacy of glucocorticoid therapy. PMID- 6243896 TI - Human polyomavirus infections with JC virus and BK virus in renal transplant patients. AB - Infection with the human polyomaviruses JC virus and BK virus was studied in 61 immunosuppressed renal transplant patients. Urine cytologic studies, indirect immunofluorescence microscopy, electron microscopy, and serologic studies were used to assess viral activity. Patients records were abstracted for events associated with polyomavirus infections. Polyomavirus excretion in urine was detected in 12 of 61 patients (20%). Eleven excreted JC virus and nine, BK virus. Fourfold hemagglutination-inhibition antibody titer rises occurred in 25 of 61 patients (41%). The serologic data suggested that most JC virus infections were primary, whereas most BK virus infections resulted from virus reactivation. During this 2-year study, 32 of 61 patients (52%) had evidence of active viral replication. Urinary tract excretion was associated with drug-requiring diabetes mellitus (P = 0.001), arterial occlusive disease (P = 0.03), and ureteral stricture with loss of renal function (P = 0.02). Antibody increases to BK virus were associated with a rising seurum creatinine (P = 0.02) and need for transplant biopsy (P = 0.02). Polyomavirus replication was therefore associated with an increased frequency of transplant related complications. PMID- 6243897 TI - Endocrine aspects of aging. PMID- 6243898 TI - [Biological activity of a new Soviet natural inducer, double-stranded RNA]. AB - Antiviral activity of a two-spiral RNA (ts RNA), a new natural interferon inductor was studied. It was shown that ts RNA extracted from a phage infected E. coli culture was an active inductor of interferon and resistance to infection with the forestspring encephalitis virus experimental animals. In experiments on 10-12 g mice ts RNA administered in a dose of 50 micrograms/mouse 6 hours after the infection induced up to 1280 units/ml of the serum interferon. When the inductor was administered repeatedly, the experimental animals developed hyporeactivity resulting in a marked decrease in interferon production after the 3rd subsequent injection. The most pronounced effect with respect to the forest spring encephalitis virus was observed when the inductor was administered intraperitoneally in a dose of 20 micrograms/mouse 4 hours before the infection. The protective effect was less pronounced when the inductor was administered 24 and 48 hours before the infection. A two-fold administration of the inductor did not increase the antiviral effect. When the inductor was administered in a dose of 100 micrograms 14 days before the infection, the animals showed an increase in the nonspecific resistance to the infection resulting in a marked antiviral effect. PMID- 6243899 TI - Stability of simian rotavirus in fresh and estuarine water. AB - The rates of inactivation of poliovirus 1, echovirus 7, coxsackievirus B3, and simian rotavirus SA11 were compared in polluted and nonpolluted fresh and estaurine water samples. The study was done in two parts, comparing virus survival in samples taken 1 year apart from the same sites. The survival studies were performed at 20 degrees C and at the natural pH of the water samples. In the first part of the study, the time required for a 3-log10 reduction in the initial virus titers was 2 to 3 days in the estaurine water samples and varied from 3 to greater than 14 days in the freshwater samples. In the second part of the study, no clear distinction was found between survival of viruses in freshwater samples and survival in estaurine water samples. The time required for a 3-log10 reduction in the initial virus titers in the second part of the study varied from 12 to greater than 14 days. This indicates that there is a nonseasonal change in factors in the water which affect virus survival. In this study SA11 survival time (used as a model for human virus) was well within the range exhibited by the enteroviruses, indicating that it also is environmentally stable in natural waters. PMID- 6243900 TI - Enumeration of potentially pathogenic bacteria from sewage sludges. AB - To ascertain the health risks that may be posed by the land application of sewage sludges, a scheme was devised to determine the types and numbers of pathogenic and potentially pathogenic bacteria present in sludges. A processing treatment was adapted to sludge to give a homogenate which yielded the greatest numbers of viable bacteria. Conventional methods were successful in enumerating Klebsiella, Staphylococcus, gram-negative enteric bacteria, and commonly used indicator organisms. Modifications of conventional methods improved the enumeration of Salmonella, Mycobacterium sp., fluorescent Pseudomonas sp., and Clostridium perfringens. However, Shigella methodology yielded only one isolate. Utilizing the proposed scheme, the population densities of these organisms were estimated in three domestic wastewater sludges. In light of these results, the potential impact of land application of sewage sludges is discussed. PMID- 6243901 TI - Evaluation of the overland runoff mode of land wastewater treatment for virus removal. AB - The removal of enteric and tracer viruses by the overland runoff mode of domestic wastewater treatment was evaluated. Raw and primary and secondary treated wastewaters were sprayed onto grass-covered, 36-m soil plots of fine, sandy loam overlying an impermeable clay subsoil. Tracer bacteriophage f2 was seeded into the applied wastewaters, which were subsequently sampled at several points along the length of the plots. Assay of effluent samples revealed modest tracer virus removals of 30 to 60%. Data from timed experiments indicated that advancement of tracer virus to the bottom of the slopes proceeded at the same rate as wastewater, reaching the plot effluents within 50 to 90 min after application. Indigenous enteric virus levels were reduced by approximately 68 to 85% during migration down the treatment slopes. Soil sampling revealed that, although some f2 virus was found associated with the wastewater-saturated topsoil, little penetration of virus into the soil profile occurred. Laboratory soil adsorption studies revealed that poliovirus I was adsorbed much more readily than f2 virus. Comparison of virus removal characteristics during overland runoff with chemical removal characteristics of wastewater did not reveal any obvious correlations that could be used to predict virus removal. PMID- 6243902 TI - Improved method and test strategy for recovery of enteric viruses from shellfish. AB - An improved recovery method and testing strategy were devised for recovery of low numbers of enteric viruses from each of three commercially important shellfish species. Effective recovery of virus depended as much upon details of the test strategy adopted for use of the improved method with each species as on the method itself. The most important test details involved sample composition, pool size, and method of use of cell cultures. Recovery sensitivity measured permitted detection of 25 to 3 plaque-forming units of enteroviruses and 100 to 27 plaque forming units of reovirus through their recovery in cell culture, with effectivenesses averaging 64 and 46%, respectively. Test samples prepared by the improved recovery method were virtually cytotoxicity free. Optimal recovery of virus on 45-cm2 cell culture monolayers was obtained with 1-ml inocula adsorbed for 2 h. The most effective recovery of virus from shellfish samples was made by a sequential adsorption procedure which allowed equal exposure of an entire sample to each of two or more cell cultures. Removal of nonviral contaminants from test samples by antibiotic treatment was preferable to the use of ether or membrane filtration procedures. PMID- 6243903 TI - Large-scale purification of Japanese encephalitis virus from infected mouse brain for preparation of vaccine. AB - Large volumes of Japanese encephalitis (JE) virus propagated in mouse brain can be easily purified by polyethylene glycol 6,000. By using the polyethylene glycol precipitation method, mouse hemoglobin was almost all separated from the viral suspension, and consequently the total amount of nonviral protein in the viral suspension decreased. The recovery of infectivity was about 100%. The removal of residual polyethylene glycol in the viral suspension was possible without difficulty by means of ethanol precipitation. This method is recommended as an initial step in large-scale purification of Japanese encephalitis virus propagated in mouse brain because it is simple, rapid, and inexpensive. PMID- 6243904 TI - Glycogen metabolism in myogenic cells in culture. Presence of inhibitors for dephosphorylation of glycogen synthase and glycogen phosphorylase. PMID- 6243905 TI - Temperature-dependent paramagnetism in melanin polymers. PMID- 6243906 TI - CRP, immunologically cross-reacting protein of prolyl hydroxylase. Its role in assembly of active pro-yl hydroxylase and cellular localization in L-929 fibroblasts. PMID- 6243907 TI - Modification of an essential arginine of carbamate kinase. PMID- 6243908 TI - Substrate and metal ion binding to carbamate kinase: NMR and EPR studies. PMID- 6243909 TI - Collagenase production by primary cultures of rat uterine cells. Partial purification and characterization of the enzyme. PMID- 6243910 TI - Ontogenesis and independent genetic control of the rat adenylate kinase isozymes (EC 2.7.4.3.). PMID- 6243911 TI - Cutaneous reactions at test sites of iodine-containing contrast medium. PMID- 6243912 TI - Plasma ACTH, cortisol, LH, FSH, testosterone, and dihydrotestosterone responses to bromocriptine in normal men. AB - The effects of an initial oral 2.5 mg dose of bromocriptine and of a similar dose after treatment with 2.5--5 mg daily for one week on plasma concentrations of ACTH, cortisol, LH, FSH, testosterone, and dihydrotestosterone were studied in normal men. In addition to its suppressive effects on plasma concentrations of prolactin and catecholamines which have been reported previously, a single dose of bromocriptine produced small increases in plasma ACTH and cortisol. Neither a single dose of bromocriptine nor treatment for one week altered plasma concentrations of LH and FSH. Plasma concentrations of testosterone and dihydrotestosterone were not altered by a single dose of bromocriptine, but small increases in both were noted in some subjects after treatment for one week. PMID- 6243913 TI - Spermatozoal hapten gained via autolysis. AB - Using autolysis different spermatozoa surface peptides were solubilized. The resulting low molecular weight compounds were further separated by gel chromatography on Biogel P-4, thin-layer chromatography on Cel 400 and thin-layer electrophoresis. After the conjugation of the compound with cytochrome C a conformation-independent determinant was detected with immuno-electrophoresis. Out of the 17 fractions tested only fraction 3, with a molecular weight of 1800 daltons revealed a precipitation reaction with human sperm-immobilizing sera and rabbit antihuman sperm-serum. All 17 fractions showed no precipitation reaction against human sperm-agglutinating sera. PMID- 6243914 TI - Treatment of genital herpes simplex virus in male patients. AB - Twenty-three male patients with herpes simplex virus type 2 blisters on the prepuce, glans penis, and penile shaft were divided into 2 groups. Ten patients served as controls, and thirteen patients were treated with ultrasound (1 W/cm2 for 60 sec) and Herpigon on 3 consecutive days. Results showed a negative virus culture after 3 days of treatment and significant reduction of the recurrent infection in the treated group while the control group experienced recurrent infection within 62--80 days. This method offers a new therapeutic treatment for genital herpes simplex virus. PMID- 6243915 TI - Ultrastructure of the conjunctiva, skin, and gingiva: a case of Sandhoff's disease in a Jewish patient. AB - Pleomorphic membranous cytoplasmic bodies that indicated glycolipid storage were found in the conjunctiva, skin, and gingiva of a Jewish patient with Sandhoff's disease. The clinical symptoms were typical of GM2 gangliosidosis. Both hexosaminidase A and hexosaminidase B activities were deficient in the leukocytes and serum. Glycosaminoglycan levels in cultured fibroblasts were elevated. Membranous cytoplasmic bodies were observed in high concentrations in a large proportion of the vascular endothelial cells, pericytes, and Schwann cells and to a somewhat lesser extent in the fibrocytes of all tissues studied. Ultrastructural analysis of the conjunctiva, skin, and gingiva as an aid for the diagnosis of Sandhoff's disease is suggested. PMID- 6243916 TI - Polyglycolic acid, silk, and topical ampicillin. Their use in hernia repair and cholecystectomy. AB - The effect of topical ampicillin sodium and polyglycolic acid and silk sutures on the recurrence of an existing hernia or an incisional hernia and on infection rates in clean abdominal wounds (herniotomies and simple cholecystectomies) was studied in a triple-blind, randomized trial with 398 consecutive patients. One infection, three suture sinuses, and two incisional hernias occurred among 113 patients with cholecystectomies, while the corresponding rates in 285 patients with hernia repairs were 11 infections, no suture sinuses, and three recurrent hernias. No effect of ampicillin could be demonstrated, nor was any difference between polyglycolic acid and silk sutures shown. No interaction between the antibiotic and suture material was found, and no side effects were observed. Wound infection was significantly more frequent in patients with postoperative seromas or hematomas. PMID- 6243917 TI - Differentiation of vaccine strains and field isolates of pseudorabies (Aujeszky's disease) virus: trypsin sensitivity and mouse virulence markers. AB - Five cloned virulent North American field isolates and 2 European vaccine strains of pseudorabies (PR) viruses were compared by their sensitivity to trypsin and their virulence for mice. Marked differences in trypsin sensitivity were detected between and among virulent and vaccine PR viruses. These differences were distinct enough to characterize a virus as either sensitive or resistant to trypsin. This test also differentiated 2 virulent viruses which were previously shown to be indistinguishable on the basis of their sensitivity to thermal inactivation. Mouse virulence was evaluated by comparing the mean times-to-death of mice infected with individual viruses. Three distinct levels of virulence were observed. The two vaccine viruses were differentiated from each other and from virulent virus. Mice infected with the vaccine viruses required 23 to 118 hours longer to die than mice which were infected with virulent virus. A significant difference of 5.6 hours (P less than .005) was also detected between mice infected with 2 different field viruses. When viruses were described according to their marker profiles, 5 of 6 possible combinations were revealed. The 2 vaccine viruses could be described by separate profiles and virulent viruses could be described by 1 of 3 profiles. PMID- 6243918 TI - Characterization of herpes simplex virus strains isolated from patients with various diseases. AB - Herpes simplex virus strains (HSV) were isolated from various herpetic diseases. These HSV-strains isolated in Bulgaria (687) and in other countries (13) were studied by the neutralization test using standard type specific rabbit antisera and human gamma globulin. The serotype distribution of all strains showed: HSV-1 = 323 strains, HSV-2 = 372 strains, 5 strains behaved antigenically intermediate. A close correlation between the serotype of the strains and the localization of the lesions was established. All but four strains (1.24 per cent) isolated from the head belong to HSV-1, and only six HSV-strains (1.9 per cent) from lesions with other localizations were not HSV-2. Within six months to 8 years 2 to 4 herpes strains were isolated repeatedly from 30 patients. In 23 of these cases they were identical and in the other they showed different biological (3) or antigenical (4) properties. The results suggest, that under natural conditions some HSV-intermediate strains may exist. PMID- 6243919 TI - Human leukocyte interferon: separation of biologically different species by modification of carbohydrate moieties. AB - Human leukocyte interferon was studied to determine if its antiviral (AV) and growth inhibitory (GI) activities could be separated by enzymatic or chemical cleavage of carbohydrate moieties and electrophoretic procedures. The relative proportion of the two activities (AV:GI ratio) was determined for each gel fraction. Untreated interferon and interferon deglycosylated by glycosidases or metaperiodate were subjected to polyacrylamide gel electrophoresis in sodium dodecyl sulfate. The AV:GI ratio was similar for all fractions, indicating that no dissociation of activities was achieved based on molecular weight differences. The three preparations were then examined by isoelectric focusing to attempt separation based on charge. The untreated sample was resolved into several peaks each with a constant AV:GI ratio of 3:1. Both deglycosylated interferons showed inconstant AV:GI ratios yielding GI fractions that were enriched or depleted in AV activity. These results indicate that under the conditions used the AV and GI activities could not be separated, although molecules can be obtained that differ significantly in their relative antiviral and growth inhibitory properties. PMID- 6243920 TI - Polyacrylamide gel electrophoresis of avian rotavirus RNA. AB - The RNAs of 4 avian rotavirus isolates were analysed by polyacrylamide gel electrophoresis. One of these isolates was made from chickens, the other three were from turkeys. The RNAs were separated into 8 or 9 bands consisting of 11 segments, ranging in molecular weight from 0.24 X 10(6) to 2.09 X 10(6). In contrast to calf rotavirus, segments 10 and 11 of avian rotavirus RNA had very similar or identical electrophoretic mobilities. This may be a unique feature of avian rotavirus RNA. Co-electrophoresis experiments showed that the RNAs of 2 of the turkey isolates were electrophoretically identical. However, differences existed between these 2 isolates, the chicken isolate and the remaining turkey isolate with respect to segments 5, 6, the 7, 8, 9 complex and 10. Segment 5 of the chicken isolate was sometimes resolved into 2 components, and was further anomalous in that it was absent in some (analyses). PMID- 6243921 TI - Occurrence of Hsw 1 N 1 subtype influenza A viruses in wild ducks in Europe. AB - Two identical strains of influenza A viruses antigenically related to swine influenza (Hsw 1 N 1) have been isolated from adult mallard ducks (Anas platyrhynchos) in Southern Germany. They were designated A/Duck/Bavaria/1/77 and A/Duck/Bavaria/2/77. Serologic tests revealed a close antigenic relationship to the strain A/Duck/Alberta/35/76. Experimental infections of piglets with strain A/Duck/Bavaria/1/77 demonstrated the susceptibility of swine to this virus strain. The virus was isolated from nasal swabs of infected piglets up to 8 days p. inf. and from contact animals up to 9 days. No seroconversion was detected during an observation period of 30 days. PMID- 6243922 TI - Characterization of a foot-and-mouth disease mutant temperature-sensitive for viral RNA synthesis. AB - A temperature-sensitive (ts) mutant of foot-and-mouth disease virus (FMDV) did not produce RNA polymerase activity nor synthesize viral RNA when incubated in cells solely at the nonpermissive temperature (38.5 degrees C). Infected cells initially incubated at 38.5 degrees C and then shifted down to 33 degrees C synthesized increased amounts of viral RNA at earlier times compared to infected cells kept at 33 degrees C throughout, indicating that RNA polymerase precursors were synthesized at 38.5 degrees C. In cells shifted up to 38.5 degrees C from 33 degrees C, the total amount of viral RNA synthesized after infection increased sharply for about 15 minutes and then rapidly increased over the next 2 hours. RNA polymerase activity presented a similar pattern in its initial twofold increase and subsequent rapid decrease. Pulse labeling experiments showed that mutant viral RNA synthesis continued at a diminishing rate for 2 hours in cells shifted up to 38.5 degrees C. The data from temperature after shift-up was degraded. The FMDV ts mutant is apparently additionally defective in being unable to protect viral RNA synthesized after shift-up to 38.5 degrees C. PMID- 6243923 TI - Virion polypeptides of poxviruses. AB - Structural polypeptides from a number of poxviruses were analysed by SDS polyacrylamide gel electrophoresis. The patterns obtained with orthopoxviruses were generally quite similar to one another, but variola, monkeypox, cowpox and vaccinia viruses could be distinquished by their profiles in the molecular weight (mol. wt.) region around 30,000 to 40,000; some additional variation was found amongst cowpox and vaccinia strains. Whitepox virus was shown to have structural polypeptides indistinguishable from those of variola virus. The structural polypeptides of poxviruses belonging to other genera were different from those of the orthopoxvirus, except those of mol. wt. about 122,000 and 97,000, which were common to all viruses irrespective of genus. A polypeptide of mol. wt. about 25,000 was also observed in all cases, though its position varied slightly with the individual virus. PMID- 6243924 TI - Aujeszky's disease in the guinea pig: cellular and humoral responses following immunization. AB - The fatal disease caused by virulent ADV in guinea pigs was found to be identical to that seen in sheep and cattle. Intramuscular (i.m.) injection of an avirulent strain of ADV (Bartha) yielded better immunity to challenge after 3 weeks than did intranasal (i.n.) immunization, and this was reflected in differences in histopathological changes in the brain. Serum antibodies active in antibody dependent cell-mediated cytotoxicity (ADCC) were titrated using polymorphonuclear leukocytes as effector cells. ADCC correlated fairly well with virus neutralization and was a far more sensitive technique. There was good, but not complete, correlation between ADCC and protection. Lymphocyte responsiveness to virus antigens in vitro was assessed by 3H-thymidine uptake and lympholine tests. Lymphocyte stimulation and mitogenic factor responses were low grade but blood lymphocyte stimulation was more pronounced in the better-protected animals. Macrophage migration inhibition correlated neither with serum ADCC nor with protection, being equally demonstrable in the two immunized groups. PMID- 6243925 TI - Avian infectious bronchitis virus structural polypeptides: effect of different conditions of disruption and comparison of different strains and isolates. AB - Variations in the conditions used for disruption of purified virus involving differences in heat treatment and reducing agent concentration produced little affect on the polypeptide profiles of the Massachusetts 41 (M 41) strain of avian infectious bronchitis virus obtained by polyacrylamide gel electrophoresis. Comparisons of the structural polypeptides of 12 IBV isolates, consiting of M 41, six serologically related viruses and representatives of five other serotypes, showed that the viruses could be placed in three groups on the molecular weights of the major glycopolypeptides. These were 31,000 and 86,000 for M 41, the six related viruses and the serologically distinct SE 17; 27,000 and 89,000 for Iowa 97 and Holte and 27,000 and 91,000 for Connecticut and T strain. PMID- 6243926 TI - Antagonism in action between mouse or human interferon and platelet growth factor. AB - Human leukocyte and mouse fibroblast interferons abolished the mitogenic effect of human or bovine platelet growth factor (PGF) on human or mouse cells. Conversely, the antiviral and anticellular activity of both forms of interferon was inhibited by PGF in the homologous and in certain heterologous cell systems. PMID- 6243927 TI - The 5' end of foot-and-mouth disease virion RNA contains a protein covalently linked to the nucleotide pUp. AB - Foot-and-mouth disease (FMD) virion RNA contains a protein covalently linked to its 5' end. This protein has a molecular weight of approximately 12,000 daltons and is linked to the nucleotide pUp. PMID- 6243928 TI - Interferon production and virus replication in lymphoblastoid cells infected with different viruses. AB - A semicontinuous infection system was used to test viral replication and interferon induction in lymphoblastoid cells: measles virus, Newcastle disease virus (NDV), Sendai virus, human parainfluenza virus (type II and III), Semliki forest virus (SFV) and Vesicular stomatitis virus (VSV). With the exception of Sendai virus, all viruses replicated in the Namalva cell line. Only measles virus was able to induce high levels of interferon. Three other cell lines, NC37, Raji (TK+-variant) and Raji (TK--variant) were tested using measles virus as inducer. The interferon yields from these cells were inferior to those obtained from Namalva cells. PMID- 6243929 TI - Familial infantile myasthenia. AB - Familial infantile myasthenia is a rare type of myasthenia that usually occurs in connection with respiratory depression. The condition is characterized by (1) absence of myasthenia in the mother, (2) occurrence of a similar disorder among siblings, (3) respiratory depression at birth, (4) episodic weakness and apnea during the first two years of life, and (5) improvement with age. Since the condition responds to anticholinesterase medication, early diagnosis is important. Familial infantile myasthenia is a potential cause of sudden infant death and should be considered in infants with unexplained respiratory distress. PMID- 6243930 TI - Epstein-Barr virus antibodies in multiple sclerosis. AB - Serum antibody titers to Epstein-Barr virus (EBV), an agent that persists in a latent form after the initial infection, were determined in 157 patients with multiple sclerosis and in 81 control subjects. Two patients (1.3%) and five control subjects (6.2%) lacked antibodies to EBV. In the subjects with antibodies, the prevalence of high titers (greater than or equal to 1:160) was significantly greater in patients, 69 (44.5%), than in control subjects, 22 (28.9%). The geometric mean titer of antibodies to EBV was significantly higher in patients, 107.0, than in control subjects, 77.1. There was no association between antibody titers and duration or activity of the disease. These findings further support the contention that patients with multiple sclerosis have a general aberration of the immunological system. PMID- 6243931 TI - Multiple sclerosis and serial computerized tomography. Delayed contrast enhancement of acute and early lesions. AB - By demonstrating periventricular contrast-enhanced lesions cranial computerized tomography (CT) supported the diagnosis of multiple sclerosis in a patient with recurrent transient hemiparesis. These abnormalities were present only on delayed films taken one hour after contrast injection and probably represented acute and early demyelinating plaques. Areas of contrast enhancement evolved to isodensity with and without corticosteroid treatment. Brain scan findings mirrored cranial CT abnormalities, and both could be correlated with the clinical status and the course of the disease. PMID- 6243932 TI - Glomus jugulare and hereditary hemorrhagic telangiectasia. PMID- 6243933 TI - The autosomal form of phosphorylase kinase deficiency in man: reduced activity of the muscle enzyme. PMID- 6243934 TI - Induction of both cytochromes P-450 and P-448 by 2,3',4,4',5-pentabromobiphenyl, a component of fireMaster. PMID- 6243935 TI - Metabolic inhibitors increase prolactin binding to cultured mammary tumor cells. PMID- 6243936 TI - Involvement of superoxide in the reactions of the catechol dioxygenases. PMID- 6243938 TI - EPR study of the effect of formate on cytochrome C oxidase. PMID- 6243937 TI - Activation of myosin light chain kinase by trypsin. PMID- 6243939 TI - Autophosphorylation of brain microtubule protein: evidence for endogenous protein kinase/phosphoprotein phosphatase cycling and multiple phosphorylation of a microtubule associated protein. PMID- 6243940 TI - Internal EcoRI-generated deletion in prophage Mu DNA. PMID- 6243941 TI - Mapping cyclic AMP binding sites on type I and type II cyclic AMP-dependent protein kinases using 2-substituted derivatives of cyclic AMP. PMID- 6243942 TI - Evidence that carnosine and anserine may participate in Wilson's disease. PMID- 6243943 TI - Non-random cleavage of SV40 DNA in the compact minichromosome and free in solution by micrococcal nuclease. PMID- 6243944 TI - Mechanism of inhibition of translocation by kanamycin and viomycin: a comparative study with fusidic acid. PMID- 6243945 TI - Role of cyclic AMP in mitochondriogenesis in yeast. PMID- 6243946 TI - Dephosphorylation of rabbit skeletal muscle glycogen synthase by phosphoprotein phosphatase and human placental alkaline phosphatase. PMID- 6243947 TI - Effect of 3T3 plasma membranes on cells exposed to epidermal growth factor. PMID- 6243948 TI - [Brain tumor and cyclic nucleotides. I. Concentrations of cyclic AMP and cyclic GMP in various brain tumors (author's transl)]. PMID- 6243949 TI - Molecular weight and hydrodynamic parameters of the adenosine 5'-diphosphate- adenosine 5'-triphosphate carrier in Triton X-100. PMID- 6243950 TI - Modulation of the reconstituted adenine nucleotide exchange by membrane potential. PMID- 6243951 TI - Dynamic properties of binary mixtures of phosphatidylcholines and cholesterol. AB - We have observed the paramagnetic resonance spectra of a head group spin-labeled phosphatidylethanolamine (L-alpha-dipalmitoylphosphatidyl-N-ethanolamine) as a function of temperature and cholesterol concentration in binary mixtures of cholesterol and dimyristoylphosphatidylcholine. These spectra bear on two interrelated topics involving mixtures of phosphatidylcholine and cholesterol: (1) lipid phase equilibria and the lateral ordering and diffusion of lipid molecules and (2) model membrane immunochemistry using spin-label lipid haptens. PMID- 6243952 TI - Hydrolysis of di- and trisialo gangliosides in micellar and liposomal dispersion by bacterial neuraminidases. AB - The hydrolysis of di- and trisialo gangliosides by bacterial neuraminidases was investigated. Slow rates of hydrolysis were obtained with micellar dispersions of the pure gangliosides; the rates increased considerably with mixtures of ganglioside and phospholipids, such as phosphatidylcholine or sphingomyelin. The greatest rates of hydrolysis were obtained with mixtures containing 5-10 mol% ganglioside and 90-95% phospholipid. With the aid of the nonpenetrating reagent trinitrobenzenesulfonic acid, it was ascertained that this mixture consisted of sealed, unilamellar vesicles in which the ganglioside was distributed symmetrically between the two layers of the liposome. When the relative proportion of the ganglioside was increased, the dispersions contained liposomes admixed with micelles of ganglioside and phospholipid. The rates of hydrolysis of the ganglioside could be correlated with the percentage of sealed vesicles in each mixture. Experiments in which another ganglioside (GM1) or cholesterol was incorporated into the mixed dispersions further supported this conclusion. It is suggested that the rate of hydrolysis is affected predominantly by interactions between the carbohydrate chains of ganglioside molecules. The data emphasize that ganglioside metabolism can be best studied when the latter are part of biological or model membranes. PMID- 6243953 TI - Studies on the mechanism of adenosine 5'-monophosphate inhibition of bovine liver fructose 1,6-bisphosphatase. AB - Inhibition by adenosine 5'-monophosphate (AMP) of the forward reaction of fructose 1,6-bisphosphatase (FBPase) has been studied by means of progress curve analysis. The full time course of the FBPase reaction was followed by coupling the reaction to the enzymes phosphoglucoisomerase and glucose-6-phosphate dehydrogenase. The data were analyzed by using three different methods of regression and these methods are compared. During these progress curve experiments, it was noticed that fructose 1,6-bisphosphate (Fru-P2) was not fully utilized in the presence of AMP. This anomaly could be best explained by proposing the formation of an AMP.Fur-P2 complex that was inactive with FBPase. Besides reducing the level of substrate available to FBPase, AMP caused slope parabolic, intercept-parabolic noncompetitive inhibition with respect to Fru-P2. A kinetic model for AMP inhibition of the forward reaction of FBPase is presented. Initial rate kinetics were used to study the reverse reaction of FBPase; AMP was a slope-parabolic, intercept-parabolic noncompetitive inhibitor with respect to both fructose 6-phosphate and inorganic phosphate. Initial velocity experiments in which both fructose 6-phosphate and inorganic phosphate were varied were carried out in the absence and presence of AMP. The results of these experiments indicated to which reverse-reaction enzyme forms AMP was binding. The possible physiological significance of the AMP inhibition of FBPase and of the proposed AMP.Fru-P2 complex is discussed. PMID- 6243954 TI - Saturation transfer electron spin resonance spectroscopy as a probe of anisotropic motion in model membrane systems. PMID- 6243955 TI - Phosphoglycerate mutases: stereochemical course of the phosphoryl group transfers catalyzed by the cofactor-dependent enzyme from rabbit muscle and the cofactor independent enzyme from wheat germ. AB - 2-[(R)-16O,17O,18O]Phospho-D-glycerate has been synthesized and used to determine the stereochemical course of each of the two mechanistic classes of phosphoglycerate mutases. The enzyme from rabbit muscle requires 2,3-bis-phospho D-glycerate as a cofactor and catalyzes an intermolecular phosphoryl group transfer reaction. The enzyme from wheat germ requires no cofactor and catalyzes an intramolecular transfer of the phosphoryl group. We have shown that the reaction catalyzed by each of these enzymes proceeds with overall retention of the configuration at phosphorus. This stereochemical result is consistent with a double-displacement pathway involving a single phosphorylenzyme, for each of the catalyzed reactions. PMID- 6243956 TI - Inhibition of ribonucleic acid accumulation in mouse L cells infected with vesicular stomatitis virus requires viral ribonucleic acid transcription. AB - The accumulation of ribonucleic acid (RNA) in mouse L-929 cells infected with temperature-sensitive mutants of vesicular stomatitis virus or ultraviolet- (UV-) irradiated virus was studied. At the permissive temperature (30 degrees C infection by all mutants resulted in an inhibition of cellular RNA accumulation. At the nonpermissive temperature (40 degrees C) mutants G114 (I) and G22 (II) failed to inhibit RNA accumulation, but mutants G11 (I), O52 (II), G31 (III), G33 (III), G41 (IV), W10 (IV), O45 (V), and O110 (V) were still active in this respect. In most cases the accumulation of 28S and 18S mature rRNA was inhibited to a greater extent than the synthesis of the 45S rRNA precursor. UV irradiation of wild type virus considerably reduced its capacity to inhibit cellular RNA synthesis. The target size for inactivation of this capacity of the virus was approximately 17% of the viral genome or that corresponding to the N gene. These results indicate that the virion proteins themselves are incapable of inhibiting cellular RNA synthesis and that transcription of approximately 17% of the genome is required. Expression of RNA synthesis inhibition also requires some function of virion NS protein in addition to its transcriptase activity. PMID- 6243957 TI - Reconstitution of HeLa cell poly(adenosine diphosphate ribose) polymerase with purified oligonucleosomal chromatin. PMID- 6243958 TI - Adenosine cyclic 3',5'-monophosphate uptake and regulation of membrane protein kinase in intact human erythrocytes. AB - The uptake of adenosine cyclic 3',5'-monophosphate (cAMP) and stimulation of membrane-associated protein kinase in mature human erythrocytes were investigated. cAMP transport across the membrane was temperature dependent, and cAMP binding to the isolated membrane had less temperature dependence. More than 99% of the [3H]-cAMP taken up by erythrocytes was nonmembrane bound. Maximal stimulation of membrane protein kinase and maximal occupancy of membrane cAMP binding sites by extracellular cAMP cccurred at 30 degrees C within 30 min after initiation of the incubation of erythrocytes with cAMP. The concentration of extracellular cAMP that gave half-maximal stimulation of membrane protein kinase was 5.4 X 10-4 M, a value consistent with the concentrations of cAMP (5.2 X 10-4 M) found to occupy half-maximally the membrane cAMP binding sites in erythrocytes. Extracellular cAMP and to a lesser extent guanosine cyclic 3',5' monophosphate and inosine cyclic 3',5'-monophosphate stimulated membrane protein kinase in erythrocytes. The cAMP uptake by human erythrocytes as well as cAMP binding to membranes in the erythrocyte was blocked by an inhibitor [4,4' bis(isothiocyano)stilbene-2,2-disulfonate] of the anion channel. These studies indicate that cAMP can be transported across membranes into human erythrocytes and can bind to membranes to activate membrane protein kinase. It appears that there is a shared transport channel for cAMP and anion transport. PMID- 6243959 TI - Kinetic studies on the dissociation of adenosine cyclic 3',5'-monophosphate from the regulatory subunit of protein kinase from rabbit skeletal muscle. AB - The exchange rate of unlabeled adenosine 3',5'-monophosphate (cAMP) with labeled [3H]cAMP in the dimeric regulatory subunit-cAMP complex of cAMP-dependent protein kinase, type I, purified from rabbit skeletal muscle is described by using the equilibrium isotope exchange technique. Results indicate that the rate of exchange carried out in the absence of the catalytic subunit (C) is rather slow with a half-life of approximately 870 s. This slow exchange rate is not affected by the presence of MgATP (50 microM). However, when both MgATP (50 microM) and C (1-13 NM) are present, the rate of isotope exchange is observed to increase markedly. Furthermore, less than stoichiometric amounts of C are required for the increase in the rate of cAMP exchange, indicating that the effect of C on the rate enhancement is a catalytic process. These results indicate that in the presence of MgATP, a ternary complex between C and regulatory subunit-cAMP complex must be formed, and a dynamic equilibrium between the eternary complex and its dissociable species must be reached within seconds. On the basis of our kinetic data, it is proposed that the formation of this ternary complex intermediate allows the rapid activation or the inactivation of cAMP-dependent protein kinase following changes in the cellular cAMP levels. PMID- 6243960 TI - Metal ion and substrate binding to bovine galactosyltransferase. AB - Bovine milk galactosyltransferase was examined by ESR and NMR proton relaxation measurements to determine the stoichiometry and nature of manganese and UDP-Gal substrate binding. The ESR and NMR data clearly showed the binding of two (Mn(II) per mol of enzyme in the ternary complex (enzyme-manganese-UDP-Gal). The affinity of the enzyme for manganese is much higher in the presence of UDP-Gal than in its absence. A deenhancement was observed in both water and UDP-Gal proton relaxation rates upon ternary complex formation [enzyme-Mn(II)-UDP-Gal] relative to the metal-substrate [Mn(II)-UDP-Gal] binary complex, yet the temperature dependence of the water proton relaxation rate was consistent with fast exchange. A simple model was proposed which accounted for the pronounced deenhancement, involving a slow conformational interconversion of an initially formed, rapidly exchanging conformer of the enzyme-Mn(II)-UDP-Gal complex to a second form which contributes negligibly to the relaxation. PMID- 6243961 TI - Kinetics of cardiac glycoside binding to a sodium, potassium adenosine triphosphatase studied with a fluorescent derivative of ouabain. PMID- 6243962 TI - Influence of histone phosphorylation upon histone-histone interactions studied in vitro. AB - Histones H2b and H3, phosphorylated in vitro with the catalytic subunit of protein kinase I from rabbit skeletal muscle, were used to estimate the influence of histone phosphorylation upon histone-histone complex formation. Stoichiometry and interaction affinity of the complexes H2a-H2b, H4-H2b, and H4-H3 were determined by using the continuous variation method based on circular dichorism or fluorescence intensity. All complexes exhibit a 1:1 stoichiometry in sodium phosphate or sodium chloride solution of pH 7.0. The association constants of the complexes containing phosphorylated H2b were only slightly reduced, whereas that with phosphorylated H3 was strongly reduced relative to those of the nonphosphorylated species. PMID- 6243963 TI - Observations on the oxidoreduction of the two cytochromes b in cytochrome c deficient mitochondria and submitochondrial particles. AB - 1. In cytochrome c depleted mitochondria cytochrome bT is reduced rapidly upon addition of ATP or slowly during state 4 respiration, but cytochrome bK is effectively reduced in such mitochondira respiring upon glutamate plus malate in all energy states. In mitochondria or in submitochondrial particles oxidized NADH or succinate, cytochromes bK and bT were always reduced and oxidized independently. 2. Difference spectra for the two b cytochromes were obtained in the presence of respiratory chain inhibitors. Reduced cytochrome bK in the presence of cyanide can be reoxidized by CoQ2. Cytochrome bT reduced in the presence of antimycin can be reoxidized by O2 if rotenone is added to an NADH reduced sysem or malonate to a succinate-reduced system. There is no evidence for electron transfer between the two b cytochromes. 3. It is suggested that there is no electron transfer from cytochrome bT to cytochrome bK, but that a cytochrome bKbT dimer accepts electrons from the CoQ pool jointly with cytochrome c1 and another acceptor, perhaps the FeS centre. The major steady state species is b2K+b3T+, and a Q-loop occurs with reduction of CoQ by the fully reduced species b2K+b2T+. All proposed interactions between CoQ and Complex III are 2-electron processes and the change from 2-electrons to 1-electron transfer occurs within Complex III itself. PMID- 6243964 TI - The oxidation rate of high-potential c-type cytochrome in the photochemical reaction centre is temperature-independent. AB - The temperature dependence of laser-induced (694.3 nm, 30 ns, 10 mJ.cm-2) high potential cytochrome c (Em=+290 mV) oxidation kinetics was studied in Ectothiorhodospira shaposhnikovii chromatophores. It was shown that the rate constant of this reaction is independent of temperature in the range of 300 K to 120 K. PMID- 6243965 TI - Periodic changes in the oxidation state of manganese in photosynthetic oxygen evolution upon illumination with flashes. AB - The pattern of manganese released from chloroplast membranes by a rapid temperature shock after various illumination regimes indicates that changes in the oxidation state of bound manganese occur during photosynthesis. Continuous illumination decreases by 35-40% the amount of Mn(II) released in the presence of K3Fe(CN)6 compared with a dark-adapted control. Following illumination and heat treatment, the addition of the reductant H2O2 to the samples causes an increase in the level of electron paramagnetic resonance (EPR)-detectable manganese. The pH dependence of the H2O2 reduction indicates that the non-EPR-detectable manganese present in the heated sample after illumination is in the form of higher oxidation state compounds, e.g. MnO2. The light-induced Mn(II) decrease is reversible in the dark with t 1/2 approx. 40 s and can be prevented by the presence of the Photosystem II inhibitors 3-(3,4-dichlorophenyl)-1,1-dimethyl urea or fluorocarbonylcyanide phenylhydrazone during the illumination period. After a series of brief flashes of light the Mn(II) released by heat treatment oscillates over periods of four flashes. The pattern is similar to the O2 yield flash pattern and suggests that a cycling of manganese oxidation states is involved in the O2 evolution mechanism. The oscillations in the Mn(II) release are analyzed in terms of the current four-step model for O2 evolution. The analysis suggests that manganese is successively oxidized in the first two steps, but undergoes a partial reduction on the third step. This result is consistent with the concept that water undergoes a partial oxidation prior to the release of O2 from the water-splitting complex. PMID- 6243966 TI - Mitochondrial iron not bound in heme and iron-sulfur centers. Estimation, compartmentation and redox state. AB - A method is described for the assay of total mitochondrial non-heme iron and a fraction which does not belong to the iron-sulfur proteins (FeS centers) of the outer and inner membrane. The assay of the latter fraction, which is termed 'non heme non-FeS iron', is based on the formation of a chelate of Fe(II) with bathophenanthroline sulfonate in osmotically swollen mitochondria under conditions where the FeS centers are quite stable as determined by EPR spectroscopy at 20.4 K, 93 K and 123 K. The 'non-heme non-FeS iron', which in normal rat liver mitochondria amounts to approx. one third of the total mitochondrial iron (i.e. 1.7 +/- 0.3 nmol . mg-1 protein), does not represent a homogeneous pool of iron. Based on studies of its reaction with bathophenanthroline sulfonate and the dependency of this reaction on reducing agents in mitochondria and mitoplasts, evidence is presented that this non-heme iron is present in two major pools in which the inner membrane constitutes the barrier. A minor fraction (i.e. 0.4 +/- 0.2 nmol . mg-1 protein) is localized to the 'outer' compartment and a major fraction (i.e. 1.1 +/- 0.1 nmol . mg-1 protein) is localized to the 'inner' compartment and is equally distributed between the inner membrane and the matrix. The experiments described in this study also indicate that approximately half of the 'non-heme non-FeS iron' of the 'inner' pool is in the ferrous form in mitochondria as isolated, and this was not increased when oxidizable substrates were added to the mitochondria. Although the biological significance of this iron pool is not yet clear, it is likely that it represents a transit iron pool being the proximate iron donor for heme synthesis catalyzed by the enzyme ferrochelatase. PMID- 6243967 TI - Proton efflux through the chloroplast ATP synthase (CF0 . CF1) in the presence of sulfhydryl-modifying agents. AB - The rate of photosynthetic electron transport measured in the absence of ADP and Pi is stimulated by low levels of Hg2+ or Ag+ (50% stimulation approximately or equal to 3 Hg2+ or 6 Ag+/100 chlorophyll) to a plateau equal to the transport rate under normal phosphorylating conditions (i.e. +ADP, +Pi). Chloroplasts pretreated in the light under energizing conditions with N-ethylmaleimide show a similar stimulation of non-phosphorylating electron transport. The stimulations of non-phosphorylating electron transport by Hg2+, Ag+ and N-ethylmaleimide are reversed by the CF1 inhibitor phlorizin, the CF0 inhibitor triphenyltin chloride, and can be further stimulated by uncouplers such as methylamine. The Hg2+ and N ethylmalemide stimulations, but not the Ag+ stimulation, are completely reversed by low levels of ADP (2 microM), ATP (2 microM), AND Pi (400 microM). Ag+, which is a potent inhibitor of ATP synthesis, has little or no effect upon phosphorylating electron transport (+ADP, +Pi). Concomitant with the stimulations of non-phosphorylating electron transport by Hg2+, Ag+ and ADP + Pi, there is a decrease in the level of membrane energization (as measured by atebrin fluorescence quenching) which is reversed when the CF0 channel is blocked by triphenyltin. These results suggest that modification of critical CF1 sulfhydryl residues by Hg2+, Ag+ or N-ethylmalemide leads to the loss of intra-enzyme coupling between the transmembrane proton-transferring and the ATP synthesis activities of the CF0-CF1 ATP synthase complex. PMID- 6243968 TI - Reactions of mercaptans with cytochrome c oxidase and cytochrome c. AB - 1. The steady-state oxidation of ferrocytochrome c by dioxygen catalyzed by cytochrome c oxidase, is inhibited non-competitively towards cytochrome c by methanethiol, ethanethiol, 1-propanethiol and 1-butanethiol with Ki values of 4.5, 91, 200 and 330 microM, respectively. 2. The inhibition constant Ki of ethanethiol is found to be constant between pH 5 and 8, which suggests that only the neutral form of the thiol inhibits the enzyme. 3. The absorption spectrum of oxidized cytochrome c oxidase in the Soret region shows rapid absorbance changes upon addition of ethanethiol to the enzyme. This process is followed by a very slow reduction of the enzyme. The fast reaction, which represents a binding reaction of ethanethiol to cytochrome c oxidase, has a k1 of 33 M-1 . s-1 and a dissociation constant Kd of 3.9 mM. 4. Ethanethiol induces fast spectral changes in the absorption spectrum of cytochrome c, which are followed by a very slow reduction of the heme. The rate constant for the fast ethanethiol reaction representing a bimolecular binding step is 50 M-1 . s-1 and the dissociation constant is about 2 mM. Addition of up to 25 mM ethanethiol to ferrocytochrome c does not cause spectral changes. 5. EPR (electron paramagnetic resonance) spectra of cytochrome c oxidase, incubated with methanethiol or ethanethiol in the presence of cytochrome c and ascorbate, show the formation of low-spin cytochrome alpha 3-mercaptide compounds with g values of 2.39, 2.23, 1.93 and of 2.43, 2.24, 1.91, respectively. PMID- 6243969 TI - Catalytic activity and arrangement of subunit polypeptides in rat liver cytochrome c oxidase as studied by proteolysis. AB - Cytochrome c oxidase from rat liver was incubated with various proteinases of different specificities and the enzymic activity was measured after various incubation times. A loss of catalytic activity was found after digestion with proteinase K, aminopeptidase M and a mitochondrial proteinase from rat liver. In each case the decrease in enzymic activity was compared with the changes in intensities of the polypeptide pattern obtained after sodium dodecyl sulfate polyacrylamide gel electrophoresis. The susceptibilities of the subunit polypeptides of the soluble cytochrome c oxidase to proteinases were very different. Whereas subunit I was most susceptible, subunits V--VII were rather resistant to degradation. From the relative inaccessibility of subunits V--VII to proteinases it is likely that these polypeptides are buried in the interior of the enzyme complex. PMID- 6243970 TI - The pre-steady state reaction of ferrocytochrome c with the cytochrome c cytochrome aa3 complex. AB - 1. Using stopped-flow technique we have investigated the electron transfer form cytochrome c to cytochrome aa3 and to the (porphyrin) cytochrome c-cytochrome aa3 complex. 2. In a low ionic strength medium, the pre-steady state reaction occurs in a biphasic way with rate constants of at least 2.10(8) M-1.s-1 and about 10(7) M-1.S-1 (I=8.8 mM, pH 7.0, 10 degrees C), respectively. 3. A comparison of the rate constants, determined in the presence of an excess of cytochrome c with those found in the presence of an excess of cytochrome aa3 reveals the existence of two slower reacting sites on the functional unit (2 hemes and 2 coppers) of cytochrome aa3. On basis of these results we discuss various models. If no site site interactions are assumed (non-cooperative model) cytochrome aa3 has 2 high and 2 low affinity sites available for the reaction with ferrocytochrome c. If negative cooperativity occurs, cytochrome aa3 has 2 high affinity sites which change into 2 low affinity sites upon binding of one cytochrome c molecule. The latter model is favoured. PMID- 6243971 TI - Reduction of oxygen-pulsed cytochrome c oxidase by cytochrome c and other electron donors. AB - 1. Stopped-flow experiments were performed in which solutions containing dithionite were mixed with air-saturated buffer. Cytochrome c oxidase present in the dithionite-containing syringe is fully oxidized within the mixing time and the oxygen-pulsed form of the oxidase is produced. 2. The reduction of this form by dithionite, by dithionite plus cytochrome c and by dithionite plus methyl viologen or benzyl viologen was followed and compared with the corresponding reduction reactions of the "resting" oxidized enzyme. Reduction by dithionite is relatively slow, but the rate of reduction is greatly increased by addition of cytochrome c or the viologens, which are even more effective than cytochrome c on a molar basis. 3. Profound differences between the transient kinetics of the reduction of the two oxidized oxidase derivatives were observed. The results are consistent with a direct reduction of cytochrome a followed by an intramolecular electron transfer to cytochrome a3 (k1obs = 7.5 s-1 for the oxygen-pulsed oxidase). 4. The spectrum of the oxygen-pulsed oxidase formed within 5 ms of the mixing closely resembles that of the "oxygenated" compound, but there were small differences between the two spectra. PMID- 6243972 TI - Isolation and characterization of two rubredoxins from Clostridium thermoaceticum. AB - Two rubredoxins with similar molecular weights (about 6000) have been purified from Clostridium thermoaceticum, a thermophile and strict anaerobe. They exhibit minor differences in several properties like elution pattern from DEAE-cellulose column, isoelectric point, amino acid composition, absorption and EPR spectra and redox potential. Their chemical and physical properties are similar to those of other rubredoxins from anaerobic microorganisms. PMID- 6243973 TI - CO binding to mitochondrial mixed valence state cytochrome oxidase at low temperatures. AB - The kinetics and thermodynamics of the reaction of mixed valence state membrane bound cytochrome oxidase with CO over the 178-203 K range has been studied by multichannel optical spectroscopy at three wavelength pairs (444-463 nm in the Soret region, and 590-630 and 608-630 nm in the alpha region) and analysed by non linear optimization techniques. As in the case of the fully reduced membrane bound cytochrome oxidase-CO reaction (Clore, G.M. and Chance, E.M. (1978) Biochem J. 175, 709-725), the normalized progress curves at the three wavelength pairs are significantly different indicating, on the basis of Beer's law, the presence of a minimum of three optically distinct species. The only model that satisfies the triple statistical requirement of a standard deviation within the standard error of the data, a random distribution of residuals and good determination of the optimized parameters, is a two species sequential mechanism: flash photolysis of the mixed valence state cytochrome oxidase-CO complex (species IIMC) yields unliganded mixed valence state cytochrome oxidase (species EM) and free CO which then recombine to form species IMC; species IMC is then converted into species IIMC. All the thermodynamic parameters describing the model are calculated and compared to those obtained for the fully reduced membrane-bound cytochrome oxidase-CO reaction (Clore and Chance (1978) Biochem. J. 175, 709-725). Although there are some qualitative similarities in the kinetics and thermodynamics of the reactions of mixed valence state (alpha 23+Cu+B.ALPHA 3+Cu2+A) and fully reduced (a3 2+Cu B + . a2+Cu A+) cytochrome oxidase with CO, there are large and significant quantitative differences in zero-point activation energies and frequency factors; over the temperature range studied, the mixed valence state cytochrome oxidase-CO reaction is found to proceed at a significantly slower rate than the fully reduced cytochrome oxidase-CO reaction. These differences indicate that changing the valence states of cytochrome a and CuA has a significant effect on the CO binding properties of cytochrome a 3 and possibly CuB. PMID- 6243974 TI - The role of soluble cytochrome c-551 in cyclic electron flow-driven active transport in Chromatium vinosum. PMID- 6243975 TI - Electron spin echo studies on chloroplasts. Spectral characteristics of electron transport components and light-induced transients. AB - Electron-spin resonance echoes are used to study the complex overlapping ESR spectra of whole chloroplasts. By varying the repetition rate of the microwave pulse sequence, delay time, and pulse width, signals with different longitudinal and transverse relaxation times were extracted. We have identified the echo signals due to plastocyanin and ferredoxins. In addition, we have found a strong signal at g = 4.3, that possibly arises from distorted cytochrome, and weak signals in the region g = 6-9. The strong echo signal at g = 2.0047 (Signal II), is made up of at least three "dark" components that differ in their relaxation times. Upon illumination at 1.2 K several of the echo signals including Signal II show reversible light-induced components. The kinetics of these transients depend on the addition of 3(3,4-dichlorophenyl)-1,1-dimethyl urea. Part of the transients are believed to arise from cyclic electron flow around Photosystem I. PMID- 6243976 TI - Effects of glycerol on the redox properties of the electron acceptor complex in spinach photosystem I particles. PMID- 6243977 TI - Polymyxin B-phosphatidylglycerol interactions. A monolayer (pi, delta V) study. AB - Through a monolayer investigation (pi, delta V), it is shown that the cationic antibiotic polymyxin B (or E) strongly interacts with films of acidic lipids, namely the didodecanoyl- and dihexadecanoylphosphatidylglycerol. The zwitterionic dihexadecanoylphosphatidylcholine was an unsuitable substrate. Interactions occurred at and above a polymyxin B concentration in the subphase of 2.5 . 10(-7) M, bringing about a considerable increase of both pi and delta V. These interactions proceeded in two steps, as revealed by a biphasic change of delta V with time. They were independent of the film molecular packing (fluid or gel states) and of the initial film pressure. Since it was possible to monitor the relative number of polymyxin B and didodecanoyl- or dihexadecanoylphosphatidylglycerol molecules in the monolayer, it is demonstrated that, at saturation, one polymyxin B molecule is bound to five phosphatidylglycerol molecules, a result which accounts for an exact neutralization of the charges. From competition experiments, it is shown that Na+ is ineffective in removing polymyxin B from the interface. Ca2+ appeared to be a stronger competitor but no complete antibiotic desorption was observed even at a Ca2+ concentration of 100 mM. As a working hypothesis, the antibiotic/lipid (1/5) system was assumed to constitute by itself one molecular species. The mixing of the polymyxin B/didodecanoylphosphatidylglycerol (1/5) system with an excess of lipid molecules in the monolayer was found to be ideal both in terms of pi and delta V. With dihexadecanoylphosphatidylglycerol, a small condensing effect could be detected only at intermediate surface pressures, in a region where the lipid phase transition occurred. The molecular area of polymyxin B interacting with didodecanoylphosphatidylglycerol can be calculated to be 1.23 +/- 0.05 nm2. It is proposed that the whole antibiotic molecule penetrates the film, the five bound lipid molecules being distributed aroung the peptide structure, at given positions imposed by the five 2,4-diaminobutyric acid residues. PMID- 6243978 TI - Proton-induced phase separation in phosphatidylserine/phosphatidylcholine membranes. AB - Effects of ph and ionic strength on phosphatidylserine/phosphatidylcholine mixed membranes prepared on Millipore filter pore surfaces have been studied using spin labeled phosphatidylcholine. Lowering pH at constant ionic strength and lowering ionic strength at constant pH caused a lateral reorganization of the membrane. The trigger was protonation of the serine carboxyl group which caused solidification of phosphatidylserine molecules in the membrane, leaving a fluid phase consisting mainly of phosphatidylcholine. The appearent pK for the proton induced phase separation was measured in a wide range of salt concentrations. The ionic strength dependence was satisfactorily explained based on the electrostatic free energy of proton in the field of membrane surface potential. The Gouy Chapman theory gave a good approximation for the surface potential. The surface pK of phosphatidylserine and phosphatidic acid vesicles was directly measured in various salt concentrations by 31P-NMR and the results confirmed validity of the Gouy-Chapman-type analysis. The lateral reorganization was triggered by electrostatic interaction but the bulk of the stabilization energy for the structural changes would be the gains in intermolecular van der Waals energy due to closer packing of phosphatidylserine on solidification. PMID- 6243979 TI - Effect of bilayer membrane curvature on activity of phosphatidylcholine exchange protein. AB - Effect of bilayer membrane curvature of substrate phosphatidylcholine and inhibitor phosphatidylserine on the activity of phosphatidylcholine exchange protein has been studied by measuring transfer of spin-labeled phosphatidylcholine between vesicles, vesicles and liposomes, and between liposomes. The transfer rate between vesicles was more than 100 times larger than that between vesicles and liposomes. The transfer rate between liposomes was still smaller than that between vesicles and liposomes and nearly the same as that in the absence of exchange protein. The markedly enhanced exchange with vesicles was ascribed to the asymmetric packing of phospholipid molecules in the outer layer of the highly curved bilayer membrane. The inhibitory effect of phosphatidylserine was also greatly dependent on the membrane curvature. The vesicles with diameter of 17 nm showed more than 20 times larger inhibitory activity than those with diameter of 22 nm. The inhibitory effect of liposomes was very small. The size dependence was ascribed to stronger binding of the exchange protein to membranes with higher curvatures. The protein-mediated transfer from vesicles to spiculated erythrocyte ghosts was about four times faster than that to cup-shaped ghosts. This was ascribed to enhanced transfer to the highly curved spiculated membrane sites rather than greater mobility of phosphatidylcholine in the spiculated ghost membrane. PMID- 6243980 TI - Analysis of DNA from human adenovirus type 6 with restriction endonucleases HindIII, BglIII and BamHI. AB - The genome of the type 6 human adenovirus has three restriction sites for R.BamHI, thirteen for R.HindIII and ten for R.BglII. The terminal fragments of DNA cleaved by each of the enzymes have been determined by means of terminal nucleotidyl transferase and by analysis of the DNA-terminal protein complex. The sequence of the cleaved fragments has been determined by partial cleavage of DNA, simultaneous digestion of DNA with various combinations of enzymes and secondary digestion of individual isolated fragments with other enzymes. The following order of the cleaved fragments in the adenovirus type 6 genome has been found (the figures in brackets are the weights in mega-daltons): for R.BamHI-B(7.1) D(3.0)-C(4.05)-A(8.5); for R.HindIII-F(1.7)-C1(2.14)-A(3.44)-M(0.046)-I(1.24) J(0.77)-D(2.1)-E(1.96)-B(3.18)-H(1.36)-L(0.18)-C2(2.14)-G(1.44)-K(0.16); for R.BglII-E(2.07)-B(3.58)-A(4.8)-C(3.36)-I(0.78)-D(3.25)-G(1.37)-J(0.21)-F(1.85) K(0.17)-H(0.94). PMID- 6243981 TI - Cat satellite DNA. Isolation using netropsin with CsCl gradients. AB - The absence of centromeric bands in the karyotype of Felis catus is confirmed. It is also confirmed that no satellite band is visible in CsCl density gradients. However, a satellite is observed both by recentrifuging the fraction of the DNA that bands at high density in CsCl and by using netropsin to enhance the resolution of a CsCl gradient containing total F. catus DNA. The satellite, about 0.5% of total DNA, was isolated by repeated centrifugation in CsCl alone and in CsCl with netropsin. Netropsin was removed and a pure satellite DNA obtained. The reassociation kinetics (C0t1/2 less than 10(-3) M . s) show that the satellite is of the simple sequence type and hence a candidate for centromeric heterochromatin. Its cytological localisation awaits in situ hybridisation experiments. PMID- 6243982 TI - The incorporation of 5-iodo-5'-amino-2',5-dideoxyuridine and 5-iodo-2' deoxyuridine into herpes simplex virus DNA. Relationship between antiviral activity and effects on DNA structure. AB - Isopycnic centrifugation in CsCl gradients was used to quantify the incorporation of 5-iodo-5'-amino-2',5'-dideoxyuridine and 5-iodo-2'-deoxyuridine into herpes simplex virus type 1 DNA. A parallelism between the degree of incorporation into viral DNA and the inhibition of herpes simplex virus type I replication was found for both thymidine analogs. A concentration of 5-iodo-5'-amino-2',5' dideoxyuridine approximately 100 times greater than 5-iodo-2'-deoxyuridine was required to achieve similar levels of antiviral activity. However, the inhibitory effects of these compounds are similar when compared with respect to the percent of substitution for thymidine in herpes simplex virus type I DNA. Damage to the viral DNA, as indicated by the presence of single or double-stranded breaks, was assessed by centrifugation in alkaline and neutral sucrose gradients. The incorporation of 5-iodo-5'-amino-2',5'-dideoxyuridine into herpes simplex virus type I DNA produced single and, to a lesser extent, double-stranded breaks in a dose-dependent manner. 5-Iodo-2'-deoxyuridine did not, however, induced DNA breakage. These data indicate that the additional presence of a phosphoramidate bond in the DNA produced the extensive damage detected under these conditions, but that such damage is not required for antiviral activity. PMID- 6243984 TI - Inhibition of viral RNA synthesis by 1-methyl-1-nitrosourea. AB - The effect of 1-methyl-1-nitrosourea on the synthesis of viral RNA of Poliovirus in KB-cells has been examined. It was found that 1-methyl-1-nitrosourea at concentration of 400 micrograms/ml blocked the synthesis of viral RNA in Poliovirus-infected KB-cells irrespective of whether it was added to culture medium immediately after virus adsorption or 2 h later. Furthermore, the inhibitory effect of 1-methyl-1-nitrosourea on the growth of Poliovirus is comparable to that of Herpes simplex virus grown in KB-cells. These findings suggest that 1-methyl-1-nitrosourea does not discriminate between these two types of viruses and moreover that the viral RNA of Poliovirus could also be the target for the action of the drug. PMID- 6243983 TI - Helix-coil transitions in double-stranded viral RNA. Fine resolution melting and ionic strength dependence. AB - Helix-coil transitions of double-stranded RNA from reovirus and infectious bursal disease virus were measured optically in aqueous medium of different ionic strengths. In RNA from reovirus four transitions and in RNA from infectious bursal disease virus two transitions were resolved and evaluated quantitatively. The ionic strength dependence of their midpoint temperatures dTm/dlog[Na+] were 13.5 +/- 0.3 degrees C for reovirus RNA and 14.9 +/-0.7 degrees C for infectious bursal disease virus RNA. The midpoint temperatures extrapolated to 1 M ionic strength were 102.9, 104.3, 105.6, and 108.8 +/- 0.3 degrees C for reovirus RNA, and 108.8 +/- 1.8 and 109.6 +/- 1.0 degrees C for infectious bursal disease virus RNA. The G + C content of the regions in reovirus RNA melting in the different transitions were determined from the spectrum of the hypochromicity. The quantitative interpretation of the data is carried out on the basis of the ion condensation theory. It is estimated for double-stranded RNA of 100% G + C, that dTm/dlog[na+] = 8.4 degrees C. The two-dimensional dependence Tm = Tm (ionic strength, G + C content) is given. The ionic strength dependence in different double-stranded RNAs is correlated to the spacing of the phosphate backbone, secondary structure, and tertiary structure. PMID- 6243985 TI - Beta-selenaproline as competitive inhibitor of proline activation. AB - Beta-Selenaproline, a proline analog having the beta-methylene group substituted by a selenium atom, has been tested in ATP-PPi exchange reaction catalyzed by either Escherichia coli or rat liver aminoacyl-tRNA synthetases. It has been shown that with both enzymatic systems beta-selenaproline does not give rise to ATP-PPi exchange, but specifically inhibits proline activation. The inhibition is of fully competitive type and the Ki values, lower than the Km values for proline, show that beta-selenaproline binds to the synthetases with high affinity. The inability to form the complex with AMP, taking into account also the behavior of gamma-selenaproline and other proline analogs, has been ascribed to the presence of the selenium atom in the beta-position. PMID- 6243986 TI - Two sequence-specific endonucleases from Xanthomonas oryzae. Characterization and unusual properties. AB - XorI and XorII, two sequence-specific endonucleases, have been partially purified from Xanthomas oryzae. XorI and XorII were shown to be isoschizomers of PstI and PuvI, respectively. X. oryzae is a particularly good source of this PvuI isoschizomer because of the high yield of XorII, its simple purification scheme, and its relative stability. Furthermore, XorII was shown to cleave at different positions in its recognition sequence than do at least two of its known isochizomers; XorII cleaves between the C and the G at the 3'-end of its palindromic recognition sequence, 5'-CGATC G-3'. There is a single XorII site in each of the plasmid-cloning vehicles pBR313 and pBR322. Two unusual aspects of XorII digestion are discussed, namely, the kinetics of digestion of pBR313 and pBR322 and the resistance of human DNA to XorII. PMID- 6243987 TI - General and kinetic properties of pig heart mitochondrial adenylate kinase. AB - The precise localization of adenylate kinase (ATP:AMP phosphotransferase, EC 2.7.4.3) has been studied in pig heart mitochondria. This enzyme, which was distinct from the cytoplasmic enzyme, was insensitive towards SH reagents and exhibited a relatively weak inhibition by the specific inhibitor P1, P5 diadenosine-5'-pentaphosphate. The enzyme has been partially purified from isolated mitochondria. In the forward reaction adenylate kinase was very specific for AMP and less specific for the ATP site. Kinetic studies showed that in the forward direction, KMgATP and KAMP the dissociation constants of the substrates from the binary complexes were lower than the dissociation constants from the ternary complexes. In the reverse direction KMgADP was higher than KADP, but these values were not modified by the binding of the other substrate. In the forward direction, the enzyme was inhibited by excess of substrate when AMP concentrations were greater than 1 mM. This inhibition could prevent the phosphorylation of AMP to ADP and thus decrease the amount of adenine nucleotides available for oxidative phosphorylations. PMID- 6243988 TI - Purification and some properties of ATP-sulfurylase from developing sea urchin embryos. AB - ATP-sulfurylase (ATP:sulfate adenylyltransferase, EC 2.7.7.4), purified about 200 fold from sea urchin embryos, was free of ATPase and inorganic pyrophosphatase. The molecular weight of the enzyme was approx. 280 000 measured by gel filtration. The enzyme was activated by Mg2+, Ca2+ or Zn2+; EDTA and p chloromercuriphenylsulfonate inhibited the enzyme activity. The inhibition was reversed by addition of Mg2+ and dithiothreitol, respectively. The enzyme activity increased continuously as the pH was raised from 5.6 to 10.6. The Km values for the enzyme were calculated to be 13 microM for adenosine 5' phosphosulfate and 23 microM for pyrophosphate. PMID- 6243989 TI - Cooperativity of the concanavalin A inhibition of bovine milk fat globule membrane 5'-nucleotidase. Response to extraction of nucleotidase and of putative cytoplasmic surface coat components. AB - 5'-Nucleotidase (5'-ribonucleotide phosphohydrolase, EC 3.1.3.5) of bovine milk fat globules can be solubilized by deoxycholate from either isolated globule membranes or washed cream. The solubilized and membrane-bound enzymes exhibit similar Km values and are inhibited by concanavalin A by an apparent noncompetitive process. The soluble enzyme shows positive cooperativity for the inhibition (Hill coefficient of 2) at 37 degrees C, but the membrane enzyme exhibits essentially no cooperation effect. At lower temperatures (5 or 20 degrees C) the cooperative effect in the inhibition of the soluble enzyme is lost. Colchicine and cytochalasin D failed to induce cooperativity of the concanavalin A inhibition of the membrane enzyme, but induction cooperativity occurred when membranes were extracted with glycine/EDTA/mercaptoethanol, releasing a major protein component with a polypeptide molecular weight of 155 000. We suggest that the interaction of this component with the membrane imposes restraints on the behavior of the nucleotidase which are reflected in the cooperativity of the inhibition of the enzyme by concanavalin A. PMID- 6243990 TI - Multiple forms of phosphoprotein phosphatase from rabbit reticulocytes. PMID- 6243991 TI - Inhibition kinetics of three R-factor-mediated beta-lactamases by a new beta lactam sulfone (CP 45899). AB - A new beta-lactam sulfone, CP 45899, has been proved to be a time-dependent irreversible inhibitor of three R-factor-mediated beta-lactamases (penicillin amido-beta-lactamhydrolase, EC 3.5.2.6): TEM-1 (pI = 5.4), TEM-2 (pI = 5.6) and Pitton's type 2 (pI = 7.7). This inhibition occurs in two principal steps: (1) formation of a reversible enzyme-inhibitor complex (characterized by a Ki); (2) evolution of this complex into one, or more, inactive protein(s) (kinact). With the three beta-lactamases CP 45899 shows, respectively, Ki of 0.9, 0.8 and 1.8 microM and kinact of 1.2 . 10(-3), 0.8 . 10(-3) and 1 . 10(-3) s-1; the turnover numbers are: 525, 2280 and 1220. These results are compared to those previously obtained with clavulanic acid. PMID- 6243992 TI - Platelet phosphoprotein phosphatase activity. Its subcellular distribution and regulation. AB - Phosphoprotein phosphatase (EC 3.1.3.-) activity was found in human platelet homogenates and this activity was stimulated up to 20-fold by preincubation with trypsin. Both Mg2+ and Mn2+ greatly decreased the activity of trypsin-activated phosphatase but the activity of the untreated phosphatase was not affected by increasing the concentration of these divalent cations. It was also shown that the activity of the phosphatase underwent a transient inhibition upon addition of ATP and a permanent one with ATP-gamma-S. PMID- 6243993 TI - Increased beta-oxidation of erucic acid in perfused hearts from rats fed clofibrate. AB - 1. The metabolism of [14-14C]erucate and [U-14C]palmitate has been investigated in perfused heart from rats fed 0.3% clofibrate for 10 days and from control rats. 2. The total uptake of fatty acids in the heart increased in the clofibrate fed group. Clofibrate increased the oxidation of [14-14C]erucic acid by 100% and the oxidation of [U-14C]palmitic acid by 30% compared to controls. 3. The chain shortening of erucate to C20:1 and C18:1 fatty acids in the perfused heart was stimulated at least two-fold by clofibrate feeding. 4. The activity of the peroxisomal marker enzyme catalase increased 60%, the activity of cytochrome oxidase increased approx. 16% and the content of total coenzyme A increased 30% in heart homogenates from rats fed clofibrate compared to controls. 5. The isolated mitochondrial fraction from clofibrate fed rats showed an increased capacity for oxidation of palmitoylcarnitine and decanoylcarnitine, while the oxidation of erucoylcarnitine showed little change. 6. It is suggested that clofibrate increases the oxidation of [14-14C]erucic acid in the perfused heart by increasing the capacity for chain-shortening of [14-14C]erucate in the peroxisomal beta-oxidation system. PMID- 6243994 TI - A precise localization of cardiolipin in plant cells. AB - Cardiolipin and cytochrome aa3 contents of isolated plant cells (sycamore cells) and their purified mitochondria were measured. Since the cardiolipin/cytochrome aa3 ratio was the same in the intact cells and in the isolated mitochondria it was strongly suggested that cardiolipin is present only in the mitochondria. Furthermore, outer and inner mitochondria membranes of purified sycamore cells and mung bean hypocotyl mitochondria were separated and it was shown that cardiolipin is localized in the inner mitochondrial membrane. PMID- 6243995 TI - Stimulation of phosphatidylcholine synthesis by 17 beta-estradiol in fetal rabbit lung. PMID- 6243996 TI - Presence of a low molecular weight inhibitor of succinate-supported cholesterol side chain cleavage in rat ovaries. AB - 1. Low molecular weight fractions (mol. wt. 3500-10 000) prepared from cytosols of luteinized rat ovaries inhibited succinate-supported cholesterol side chain cleavage by intact ovarian mitochondria utilizing endogenous or exogenous sterol as substrate. 2. The low molecular weight fractions inhibited steroid secretion by collagenase-dispersed ovarian cells stimulated with lutropin or dibutyryl cyclic AMP. 3. Steroidogenesis by intact mitochondria incubated with NADPH was enhanced by the low molecular weight ovarian fraction, but cholesterol side chain cleavage carried out by sonicated mitochondria incubated with NADPH was unaffected. 4. Succinate-supported mitochondrial respiration was stimulated by the low molecular weight factor, apparently by uncoupling of oxidative phosphorylation. The uncoupling seems to be the mechanism by which steroid synthesis is inhibited. 5. The low molecular weight factor was heat-labile and not extracted by activated charcoal. Similar heat-labile material capable of inhibiting succinate-supported mitochondrial steroid synthesis was not found in low molecular weight fractions prepared from rat kidney, liver, spleen, brain, plasma and bovine corpus luteum. 6. Treatment of rats with cycloheximide 1 h before killing resulted in a reduction of inhibitory activity in ovarian low molecular weight cytosolic fractions. 7. We conclude that ovarian cytosols contain a low molecular weight factor, presumably a protein, which inhibits mitochondrial cholesterol side chain cleavage by uncoupling oxidative phosphorylation. The physiological function of this factor remains to be determined. PMID- 6243997 TI - Effect of vasopressin on cyclic AMP-dependent protein kinase in toad urinary bladder. AB - The effect of vasopressin on the toad urinary bladder has been shown to be mediated by cyclic AMP. It has been assumed that, as demonstrated for other systems, this involves activation of cyclic AMP-dependent protein kinase. In order to test this hypothesis we investigated the effect of vasopressin on cyclic AMP-dependent protein kinases in epithelial cells of toad bladders. About 80% of protein kinase activity and cyclic AMP-binding capacity was found to be in the cytosol. DEAE-cellulose chromatography showed a pattern of 15--20% type I and 80- 85% type II cyclic AMP-dependent protein kinase. Cytosolic kinase was activated 3 -4-fold by cyclic AMP with half-maximal activation at 5 . 10(-8) M. Similarly, half-maximal binding of cyclic AMP occurred at 7 . 10(-8) M. Incubation of toad bladders in Ringer's solution containing 0.1 mM 3-isobutyl-1-methylxanthine, prior to homogenization and assay, showed stable cyclic AMP-binding capacity and protein kinase ratio --cyclic AMP/+cyclic AMP. Exposure of bladders to 10 mU/ml of vasopressin for 10 min caused intracellular activation of protein kinase and decrease in cyclic AMP-binding capacity that were maintained for at least 30 min. Incubation of bladders with increasing concentrations of vasopressin (0.5--100 mU/ml) resulted in a discrepancy between a progressive increase in cyclic AMP levels and a levelling off at 10 mU/ml of vasopressin for the changes in protein kinase ratio and cyclic AMP-binding capacity. The increase in kinase ratio was due to higher activity in the absence of exogenous cyclic AMP and was fully inhibitable by a specific protein kinase inhibitor. Using Sephadex G-25-CM50 column chromatography for separation of holoenzyme and free catalytic subunit we demonstrated that the activation of protein kinase in the vasopressin-treated bladders is due to intracellular dissociation of the kinase. These results show that the effect of vasopressin on the toad bladder involves activation of a cytosolic cyclic AMP-dependent protein kinase. The time course and the dose response curve of the kinase activation closely parallel vasopressin's effect on osmotic water flow. PMID- 6243998 TI - Postnatal development of glycogen- and cyclic AMP-metabolizing enzymes in mammalian skeletal muscle. AB - Glycogen and cyclic AMP-metabolizing enzymes of rabbit skeletal muscle were examined during postnatal development. Glycogen synthase I, glycogen phosporylase and lactate dehydrogenase activity increased 7-fold by the 6th--8th postnatal week while glycogen synthase D was present in the neonate at one-half adult levels. Cyclic AMP phosphodiesterase decreased; adenylate cyclase increased 10 fold for both the epinephrine and NaF-stimulated states of the enzyme. PMID- 6243999 TI - Spin label partitioning in lipid vesicles. A model study for drug encapsulation. AB - In this paper we attempt to outline some features which determine the encapsulation of small molecules into lipid vesicles. Spin labels derived from five carboxylic acids of different lengths were synthesized and incorporated in varying amounts into multilamellar and unilamellar vesicles made up of four different phosphatidylcholines. The influence on the release process of the bilayer rigidity and of the hydrophobicity of the entrapped molecule was systematically studied. The hydrophobicity is of critical importance and was estimated by measuring the partition coefficient (P) between octanol and buffer. In multilamellar vesicles, molecules characterized by extreme P values (log P less than -0.3 and log P greater than 5) can be efficiently entrapped. The rate of leakage is related to the P value according to a bell-shaped curve. Moreover, gel state of the bilayer and long acyl chains of the lipids are properties which favor a good entrapment. Small unilamellar vesicles may be formed in the presence of high concentrations of hydrophilic and lipophilic spin labels. However, the formation of unilamellar vesicles produces a significant reduction of the internal volume and of the entrapped water-soluble spin lables. High fractions of lipid-soluble spin labels can be incorporated in unilamellar vesicles but the vesicle stability is diminished. PMID- 6244000 TI - Photo-induced inactivation and uncoupling of gonadotropin receptors in rat ovarian plasma membrane. AB - Suspensions of purified rat ovarian plasma membranes were irradiated by high intensity light in the cold. This treatment gradually reduced the ability of the membrane receptor to bind 125I-labeled human chorionic gonadotropin and the ability of adenylate cyclase (ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1) to respond to luteinizing hormone, follicle-stimulating hormone, human chorionic gonadotropin and prostaglandin E2. In contrast adenylate cyclase activity stimulated by NaF or guanosine 5'(beta, gamma-imido)triphosphate (p(NH)ppG) was significantly more resistant to irradiation. Human chorionic gonadotropin protected the binding site from light-induced damage, but not the ability of the hormone to activate adenylate cyclase. Irradiation destroyed close to 50% of unoccupied guanosine nucleotide binding sites but apparently did not induce massive covalent binding of nucleotides to membrane components. It is suggested that high-intensity light induces damage to two separate sites in the adenylate cyclase system. One affects hormone binding and is presumably associated with the hormone receptor, the second interferes with coupling but at a step proximal to regulation of adenylate cyclase by GTP binding protein. PMID- 6244001 TI - Properties of adenylate cyclase and cyclic nucleotide phosphodiesterase in hamster isolated capillary preparations. AB - Capillaries isolated by collagenase digestion of hamster epididymal fat pads were used to examine the properties of endothelial adenylate cyclase and cyclic nucleotide phosphodiesterase. Adenylate cyclase activity in capillary homogenates was increased by 10 microM GTP or 100 microM isoproterenol. Lower concentrations of the catecholamine and 5.7 microM prostaglandin E1 did not stimulate endothelial adenylate cyclase activity unless GTP was included in the assay system. The effects of isoproterenol on capillary adenylate cyclase activity were blocked by propranolol, but were not affected by phentolamine. Phosphodiesterase activity in endothelial homogenates showed anomalous kinetic behavior with either cyclic AMP or cyclic GMP as the enzyme substrate. At substrate concentrations below 1 microM, capillary phosphodiesterase activity hydrolyzed cyclic GMP 2-6 times faster than cyclic AMP. However, at high substrate levels, e.g., 100 microM, cyclic AMP and cyclic GMP were degraded at similar rates. Hydrolysis of 1 microM cyclic AMP by capillary homogenates was stimulated by 0.1 and 1 microM cyclic GMP. Caffeine, 1-methyl-3-isobutylxanthine, papaverine and dipyridamole SQ 20009 were effective inhibitors of capillary phosphodiesterase activity. In contrast, imidazole enhanced the activity of the enzyme. The presence of adenylate cyclase and phosphodiesterase activities in hamster isolated capillaries is consistent with a role for cyclic AMP in the regulation of endothelial function. Moreover, the experiments described here indicate that hamster isolated capillaries are useful model systems for studying the metabolism of vascular endothelium. PMID- 6244002 TI - Oxytocin receptors coupled to uterine contraction in estrogen-dominated rabbits. AB - The present study investigated whether specific [3H]oxytocin binding sites previously demonstrated in estrogen-dominated rabbit uterus have properties expected of physiologic receptors coupled to uterine contraction. Microsomal membranes from estrogen-dominated rabbit uterus were found to contain high affinity specific oxytocin binding sites with Kd = 2-3 nM. These sites were predominantly myometrial in locus. Specific oxytocin binding exhibited a pH optimum between 7.5 and 8.0. Mg2+ or Mn2+ was necessary for maximal specific [3H]oxytocin binding; in contrast, Ca2+ at submillimolar concentrations inhibited specific binding. Oxytocin binding sites were not detectable in microsomal membranes isolated from progesterone-dominated rabbit uterus. Relative binding and uterotonic activities of 10 synthetic neurohypophyseal hormone analogues were determined in estrogen-dominated rabbit uterus. A qualitative correlation was observed between binding and uterotonic responses. Angiotensin II and insulin did not compete with [3H]oxytocin for uterine binding sites. It is concluded that the specific high affinity [3H]oxytocin binding sites demonstrated in estrogen dominated rabbit uterus have the selectivity for neurohypophyseal hormone analogues expected for physiologic receptors coupled to uterine contraction. PMID- 6244003 TI - Kinetics of the hormone-receptor interaction. Competition experiments with slowly equilibrating ligands. AB - Kinetics of formation of protein-tracer complex in the presence of competitor were calculated. The parameters were chosen so that they should realistically describe the in vitro association of steroid hormones with their receptors. Time necessary for equilibration depends on four rate constants in addition to initial concentrations and may be more than 1000 min. Competitors forming complexes with the protein that dissociate faster than the protein tracer complex have relative binding affinities apparently decreasing with incubation time. Conversely, relative binding affinity apparently increases with time if the protein competitor complex dissociates more slowly than the protein-tracer complex. Moreover, lack of equilibration is not easily detected. It is suggested that kinetic analyses, more detailed than usual, precede competition experiments. PMID- 6244004 TI - Effect of triiodothyronine injection on levels of triiodothyronine and thyroid stimulating hormone in sera and milk of lactating rats and in sera of their sucklings; precocious development of jejunal alpha-disaccharidases in the sucklings. AB - Administration of high doses of triiodothyronine (T3) for 4 days to lactating rats evokes an increase in T3 levels in their sera and milk, as well as in the sera of pups suckled by them. Thyroid-stimulating hormone levels in sera of mothers and sucklings are decreased. Suckling rats of T3-treated mothers exhibit a precocious increase in the activity of jejunal sucrase and maltase as well as in activity of several liver acid beta-glycosidases. PMID- 6244005 TI - Factors affecting gluconeogenesis in the neonatal subhuman primate (Macaca mulatta). AB - The capacity for gluconeogenesis has been studied in 33 subhuman primate newborn (Macaca mulatta) in the basal steady state. Basal blood glucose levels were seen to rise with increasing postnatal age. Availability of the major gluconeogenic substrates, alanine and lactate, was adequate at times when blood glucose and the rate of gluconeogenesis were low. Hepatic and renal cortical content of the four key gluconeogenic enzymes was low during the 1st week of life compared to adult levels. Diminished induction of the gluconeogenic enzymes did not appear to be the cause of low blood glucose levels. The serum-free fatty levels were directly correlated to both the basal glucose levels and to the rate of gluconeogenesis. PMID- 6244006 TI - Prematurity in the rat. I. Fuels and gluconeogenic enzymes. AB - Changes in liver glycogen, plasma glucose, lactate, alanine and glycerol concentrations during the first 2 h after delivery by cesarean section in term and preterm rats were studied. Liver glycogenolysis initiated in both groups just after delivery, the rates of glycogenolysis being about 50 mumol/h/g wet weight. Glycogen breakdown came along with very low plasma glucose concentrations suggesting that glycogenolysis could be promoted by neonatal hypoglycemia. Plasma alanine concentrations decreased in both groups at similar rates suggesting that alanine utilization was enhanced during the first 2 h of extrauterine life. The plasma glycerol concentration increased in preterm rats but no changes were observed in term rats. The plasma lactate concentration progressively decreased during the first 2 h in term rats. However, preterm rats showed no changes in plasma lactate concentrations during the first hour, then decreased during the second hour at similar rates to those observed in term rats. These results suggest that preterm rats showed a transient resistence to lactate utilization at delivery which was overcome during the first hour of extrauterine life. PMID- 6244008 TI - CSF AMP in primary affective disorder: effects of probenecid and tryptophan. PMID- 6244007 TI - Absence of transplacental passage of ACTH in the rat: direct experimental proof. AB - In order to investigate whether ACTH can cross the placenta of the rat at term, porcine 125I-ACTH was injected into mothers or fetuses. ACTH was then extracted from maternal and fetal plasma, using QUSO G-32, 2.5, 5, 10, 15, and 20 min after the injection of labelled ACTH. Plasma samples were also chromatographed on Sephadex G-50, fine, columns, 5 and 20 min after the administration of ACTH. When 125I-ACTH was injected into the mothers, the two methods used were unable to detect any radioactivity associated with intact ACTH in the fetal plasma. The same was observed in the maternal plasma when labelled hormone was administered to the fetuses. These observations provide direct experimental proof of the absence of transplacental passage in the rat of 125I-ACTH from the mother to the fetus as well as from the fetus to the mother. PMID- 6244009 TI - Anomalous behavioral response to imidazoleacetic acid, a GABA agonist, in animals treated chronically with haloperidol. AB - Short-term haloperidol treatment decreases the stimulant effects of drugs with dopaminelike actions, while withdrawal from long-term haloperidol treatment enhances the effects of such drugs. In the present study, we have shown that withdrawal from long-term haloperidol treatment decreases or eliminates the tendency for imidazole-4-acetic acid, a GABA agonist, to decrease the locomotor activity of mice. Acute haloperidol treatment did not duplicate these effects. It is suggested that chronic administration of haloperidol causes changes in a variety of systems in the brain, and that the GABA system in particular is profoundly altered by such treatment. PMID- 6244010 TI - Partial inhibition by lithium of the epinephrine-stimulated rise in plasma cyclic GMP in humans. AB - Lithium-treated and drug-free individuals were each given 0.5 mg epinephrine subcutaneously and blood samples withdrawn for measurement of plasma cyclic AMP and cyclic GMP. The rise in plasma cyclic GMP in response to epinephrine was found to be partially inhibited by lithium treatment, and previous reports of lithium inhibition of the plasma cyclic AMP rise were replicated. Effects of lithium on cyclic AMP and cyclic GMP may relate to lithium's biphasic efficacy in depression and mania. PMID- 6244011 TI - Lithium enhancement of central 5-HT transmission induced by 5-HT precursors. AB - The effects of acute and chronic lithium chloride administration on synaptic transmission between bulbospinal norepinephrine (NE) or 5-hydroxy-tryptamine (5 HT) pathways and sympathetic preganglionic neurons were tested in unanesthetized, spinal cats. Discharges recorded from sympathetic preganglionic white rami were evoked by stimulation of spinal reflex pathways or descending excitatory pathways in the cervical spinal cord. Acute lithium administration (2 meq/kg) produced insignificant depression of the reflex pathway but markedly depressed transmission through the intraspinal pathway, an effect that was prevented by depletion or blockage of 5-HT. These observations and the failure of lithium to alter the typical effects of L-dopa on both pathways indicate that lithium does not affect transmission through the excitatory NE pathway. L-Tryptophan (1,0 mg/kg) alone produced little or no depression of either pathway, but 3--4 hr after lithium, this dose of L-tryptophan gradually depressed transmission through both pathways by about 20%. After chronic lithium pretreatment (1 meq/kg twice a day for 3 days), L-tryptophan rapidly depressed transmission through spinal reflex and intraspinal pathways by 40% and 50% respectively. Chronic lithium pretreatment also more than doubled the depression of transmission through both pathways produced by 30 mg/kg of 5-HTP. The average of plasma lithium levels 8- 10 hr after the last chronic dose was 1.5 meq/liter. These results support the proposal that lithium increases the uptake of L-tryptophan and 5-HTP by central 5 HT terminals and thereby enhances 5-HT synthesis which is reflected in increased transmission at central 5-HT synapses. PMID- 6244012 TI - Activation of the guinea pig granulocyte NAD(P)H-dependent superoxide generating enzyme: localization in a plasma membrane enriched particle and kinetics of activation. AB - The subcellular localization, kinetics of activation, and substrate specificity of the guinea pig granulocyte superoxide (O2-) generating system was investigated. Membrane-enriched particles (podosomes) were made from granulocytes by mild sonication and differential centrifugation. These podosomes are enriched threefold for known plasma membrane markers, 5'-nucleotidase, and adenylate cyclase. Podosomes made from resting granulocytes have very little NAD(P)H dependent O2- production. Podosomes made from cells stimulated with digitonin are equally enriched for membrane markers but have a 15- to 20-fold increase in NAD(P)H-dependent O2- production. The KmAPP for NADPH is one-tenth that for NADH, but the Vmax is the same. The kinetics of digitonin-stimulated whole-cell O2- production parallel the changes in enzyme activity in these podosomes. Temperature affects both the rate and extent of activation of this enzyme. The pH optimum for the enzyme, the pH optimum for activation, and the pH optimum for whole-cell O2- production are all 7.5. Enzyme activity is increased if the cells are treated with glucose and cyanide, inhibited in cells treated with 2 deoxyglucose (2-DOG), and requires the presence of calcium for activation. These effects are similar to those found for granulocyte O2- production. Thus, the granulocyte O2- generating enzyme system is located on a fraction enriched for plasma membrane markers, and the kinetics of granulocyte production are directly related to the rate and amount of activation of this enzyme. PMID- 6244013 TI - Mitogen requirements for the in vitro propagation of cutaneous T-cell lymphomas. PMID- 6244014 TI - Functional and metabolic studies of polymorphonuclear leukocytes in the congenital Pelger-Huet anomaly. AB - Polymorphonuclear leukocytes (PMNL) from two individuals with congenital Pelger Huet anomaly (PHA) were examined to determine whether functional or metabolic defects accompanied the known morphological abnormality. No abnormalities of the PHA cells, as compared to normal control cells, were found when tested for quantitative leukocyte enzyme activities, nitroblue tetrazolium reduction, hexose monophosphate shunt activity, superoxide production, generation of chemiluminescence, or iodination. The PHA cells, as compared to normal PMNL, demonstrated normal chemotaxis and random migration, as well as bactericidal activity. PMID- 6244015 TI - Protein kinases in chronic lymphocytic leukemia. AB - Experiments were performed to characterize the protein kinase activity in blood lymphocytes from patients with chronic lymphocytic leukemia (CLL). Using histone as a substrate, the average specific activity was 397 pmole/min/mg protein. The Km for ATP was 8 muM and for histone 0.3 mg/ml. The addition of optimal concentrations of cyclic adenosine monophosphate (cAMP) (1 muM) or cyclic guanosine monophosphate (cGMP) (10muM) resulted in a 2.2-fold stimulation in activity but had no effect on the Km for ATP or histone. Most of the properties of the CCL protein kinase were similar to those of the normal lymphocyte enzyme. These include the pH response, substrate affinity, as well as rates of phosphorylation and dephosphorylation. The phosphorylation pattern of endogenous proteins was determined using intact lymphocytes incubated with 32P and cell-free homogenates with AT32P. These results indicate that: (1) the cyclicnucleotide protein kinase interactions are unimpaired in CLL lymphocytes; and (2) a sharply defined cyclic nucleotide concentration response occurs for CLL (as well as normal) lymphocytes, which may explain the reports of variable inhibitory (and stimulatory) effects on mitogenesis by these agents. PMID- 6244016 TI - Inhibition of platelet function by organic nitrate vasodilators. AB - There is evidence that platelet activation in the coronary circulation may be important in the pathogenesis of myocardial ischemia. Since organic nitrate vasodilators are commonly used in coronary artery disease, we have studied the in vitro effects of these drugs on platelet function. Nitroglycerin, isosorbide dinitrate, and their biotransformation product, inorganic nitrite, inhibited platelet aggregation with collagen, epinephrine, arachidonate, and ionophore, and blocked both primary and secondary aggregation in response to ADP. Nitroglycerin was studied in more detail. Its inhibitory effect was reversible and not dependent on external calcium concentration. It inhibited arachidonic acid oxygenation as measured by the arachidonate-induced oxygen burst and malonaldehyde production. These effects were not due to an increase in intracellular cyclic AMP. This unusual generalized inhibition of platelet function by nitroglycerin possibly contributes to its beneficial effect in myocardial ischemia in part by attenuating platelet reactivity in the coronary circulation. PMID- 6244017 TI - Heterogeneity of cell lineages in L3 leukemias. AB - Five cases of adult leukemia with L3 morphology in bone marrow were studied for the presence of immunologic, metabolic, and enzymatic markers. Among the five patients, there were four males and female. Median age was 66 with a range of 16 80 yr. Median survival was only 5 mo. Serum lactate dehydrogenase (LDH) levels, 3H-thymidine labeling indices, and DNA/RNA content of the L3 lymphoblasts were markedly elevated. B-cell markers were found in three cases, two exhibiting surface membrane IgM-lambda, and one IgG-K. Terminal deoxynucleotidyl transferase (TdT) enzymatic activity was consistently low in this group. In one case, the L3 lymphoblasts displayed only surface Fc receptors demonstrated by the binding of aggregated IgG. TdT activity was found to be significantly increased. In another instance, the lymphoblasts formed spontaneous rosettes with sheep erythrocytes and exhibited paranuclear staining with acid phosphatase. TdT activity was found to be low. Although most of the L3 leukemias are neoplasias of B lymphocytes, other lineages may also express this morphology. PMID- 6244018 TI - Alpha globin gene number: population and restriction endonuclease studies. AB - Restriction endonuclease analysis was used to test a proposed genetic model using alpha-globin gene number to account for the observed distributions of the proportions of hemoglobin (Hb) S in sickle cell trait. In a subsample of specimens collected during a population survey in India, these studies confirmed that the postulated genotype was present in 22 of the 23 individuals examined. In the study population, the number of alpha-globin genes explains about 90% of the variance in the proportion of HbS in sickle cell trait (r2 = 0.895, p less than 10(-10)). PMID- 6244019 TI - Pulmonary toxicity of beryllium in albino rat. PMID- 6244020 TI - [Does cyclic AMP play a part in the bronchodilator effect of theophylline? (author's transl)]. PMID- 6244021 TI - [Biological effects of inert gases (author's transl)]. PMID- 6244022 TI - Experimental renal hypertension and [3H]-noradrenaline release from the rabbit hypothalamus: enhanced K+-evoked overflow of tritium and lack of facilitation through presynaptic angiotensin II receptors [proceedings]. PMID- 6244023 TI - Effects of prazosin and two of its derivatives (UK 18.596 and UK 33.274) on alpha adrenoceptors [proceedings]. PMID- 6244024 TI - Are there two types of prostaglandin receptor mediating vasodilatation in the dog? [proceedings]. PMID- 6244025 TI - Alpha-adrenoceptor binding in guinea-pig lung using [3H]-prazosin [proceedings]. PMID- 6244026 TI - Interaction between prazosin and benzodioxan antihypertensives (R 28935 and R 29814); a competition for central alpha 1-adrenoceptors [proceedings]. PMID- 6244027 TI - Characterization of the beta-adrenoceptors in guinea-pig lung mast cells [proceedings]. PMID- 6244028 TI - Evidence in vitro for a 5-HT link in dopaminergic neurotransmission in the anterior hypothalamic region of the rat: demonstration of a 5-HT link in dopaminergic thermoregulation? [proceedings]. PMID- 6244029 TI - The effects of mianserine, amitriptyline, ciclazindol and viloxazine on presynaptic alpha-receptors in isolated rat atria [proceedings]. PMID- 6244030 TI - Investigations into the role of spinal alpha-adrenoceptors in cardiovascular modulation in rats [proceedings]. PMID- 6244031 TI - Enhancement of the toxic effects of veratrine on guinea-pig atrium by threshold inotropic doses of ouabain. AB - Isolated atria of guinea-pigs were treated with veratrine until the initial signs of toxicity were seen. Ouabain was then added cumulatively, starting with a threshold inotropic concentration, 50 nM, until the tissue became dysrhythmic. It was found that a concentration of ouabain which by itself gave a positive inotropic effect of only 3%, significantly enhanced the toxicity of veratrine. Veratrine had no effect on the (Na+ + K+)-adenosine triphosphatase ((Na+ + K+) ATPase) enzyme isolated from guinea-pig ventricle. The conclusion drawn is that at threshold inotropic concentrations of ouabain it is likely that the (Na+ + K+) ATPase is inhibited rather than stimulated. PMID- 6244032 TI - Distribution and function of beta-adrenoceptors in different chambers of the canine heart. AB - 1 An improved binding assay involving (-)-[(3)H]-dihydroalprenolol (DHA) and KCl washed cardiac membranes was developed to study beta-adrenoceptors in the canine heart quantitatively.2 Receptor numbers varied from 3.8 to 7.1 pmol/g fresh tissue, showing a steady increase from left atrium --> right atrium --> right ventricle --> interventricular septum --> left ventricle. With one minor exception, the same pattern was found for adenylate cyclase activity and Na(+), K(+)-activated ATPase activity.3 The binding of DHA was inhibited in the expected manner by beta-adrenoceptor agonists and antagonists, and was stereospecific, in confirmation of previous studies. Dissociation constants determined from Scatchard analyses included DHA: 2.5 nM; (-)adrenaline: 230 nM; (-)noradrenaline: 1167 nM. Kinetic analyses of the binding of DHA yielded a K(D) of about 4 nM.4 The distribution of beta-receptors is closely related to that of blood flow and the arrival plus retention of a circulating catecholamine, but is markedly different from that of endogenous noradrenaline, and thus adrenergic nerve terminals. Most receptors thus appear not at synapses but diffusely localized where they can react with circulating adrenaline.5 Evidence is discussed that beta-receptors at synapses respond primarily to neural noradrenaline, less to circulating adrenaline, and hardly at all to circulating noradrenaline; responses mediate increased cardiac output during exercise. In contrast most cardiac beta receptors appear to respond only to adrenaline, and to be used, except at times of severe circulatory stress, during psychological stress. PMID- 6244033 TI - Cardiac beta-adrenoceptors during normal growth of male and female rats. AB - 1 A binding assay involving (-)-[3H]dihydroalprenolol (DHA) and KCl-washed cardiac membranes were used to assess the numbers and affinities of beta adrenoceptors in hearts from male and female rats varying in age from about 2 weeks to 18 months. 2 Although female rats grow more slowly and attain lower adult weights than male rats, heart weights increased in approximate proportion to body weight with little sex difference. 3 As heart weight increased about three fold, beta-receptors increased three fold. Since the number of myocardial cells is believed to be nearly constant during postnatal growth, the numbers of receptors/cell presumably increases similarly. 4 As heart weight increased, the number of beta-receptors per g of tissue decreased according to the equation: total pmol/g = 4.33 - 1.43 x heart weight, equally in males and females. 5 Dissociation constants for DHA (2 to 4 nM) remained the same, and equal, in male and female rats during their growth. 6 An excellent correlation was found between the decline in beta-receptors/g tissue during growth and the decline in the area of the external sarcolemma/g tissue. The data suggest that the number of receptors per unit area remains constant during growth, and thus that cell surface area is a major factor determining normal numbers of receptors per cardiocyte. PMID- 6244034 TI - Effect of propranolol on beta-adrenoceptors in rat hearts. AB - The question of whether the chronic administration of propranolol modifies the numbers or properties of cardiac beta-adrenoceptors was examined because of many reports suggestive of cardiac hypersensitivity following the withdrawal of beta antagonists. In three studies, rats were given (+/-)-propranolol, 30 mg/day, orally or intraperitoneally, for 1 to 7 weeks. The numbers and affinities of specific binding sites for radioactive dihydroalprenolol in whole hearts from 60 control and 75 test animals were found to be the same. Thus catecholamine deprivation does not exert an important regulatory effect on most beta-receptors in the heart, as it does in the brain. PMID- 6244035 TI - Enkephalin receptor in the rabbit ileum. AB - The effects of the classical morphine-like compounds and opioid peptides on the electrically-induced contractions of the myenteric plexus-longitudinal muscle strip of the rabbit ileum were studied. The results indicate that the rabbit ileum contains the new type of opiate receptor, which is not sensitive to morphine but is sensitive to enkephalins, and provides evidence that the enkephalins may function as neurotransmitters in the intestine. The action of the enkephalins was antagonized by relatively high dose of naloxone. PMID- 6244036 TI - The factors influencing the time course of drug action at alpha-adrenoceptors: an investigation of the effects of clonidine in the pithed rat. AB - 1 The time courses of the pre- and post-junctional effects of clonidine were examined on heart rate and blood pressure and on the isometric tension responses of the vas deferens and anococcygeus in situ in the pithed rat. Plasma levels of clonidine were also monitored. 2 The time courses of the pre-junctional inhibition of sympathetic nerve mediated responses in all tissues monitored were related to the plasma levels of clonidine, but the degree of inhibition which was observed varied with the tissue and with the test stimulus employed. 3 The post junctional agonist effects of clonidine, expecially at low doses, exhibited an initial 'peak' followed by a decline to a lower plateau. This decline of the response was not due to receptor desensitization but was related to a decline in the plasma clonidine level from an initially high value caused by injection of a bolus. 4 The factors determining the time course of drugs' effects in the preparation are discussed and it is concluded that pre- and post-junctional responses should be compared at a point in time after injection of the-drug, at which equilibration has occurred. PMID- 6244037 TI - Effect of mianserin on noradrenergic transmission in the rat anococcygeus muscle. AB - 1 The effects of mianserin on the accumulation of (-)-[(3)H]-noradrenaline and on contractile responses to field stimulation, exogenously applied (-) noradrenaline, and to tyramine were studied in the rat anococcygeus muscle.2 Mianserin (10(-9) to 10(-5) M) and nortriptyline (10(-9) to 10(-5) M) inhibited the accumulation of (-)-[(3)H]-noradrenaline. In this aspect mianserin had a similar potency to nortriptyline, the most potent tricyclic antidepressant in inhibiting noradrenaline accumulation in this tissue.3 Mianserin 10(-9) or 10(-8) M alone had no effect on contractile responses to field stimulation and to (-) noradrenaline but inhibited the responses to tyramine. The responses to field stimulation at low frequencies and to (-)-noradrenaline were potentiated by 10( 7) and 10(-6) M mianserin. It is suggested that the inhibitory effect mianserin has on neuronal accumulation is primarily responsible for these effects. Mianserin 10(-5) M inhibited responses to field stimulation and to (-) noradrenaline.4 In the presence of nortriptyline (10(-6) M), the contractile responses to field stimulations were potentiated by mianserin (10(-8), 10(-7) and 10(-6) M), 10(-8) M being the most potent in this aspect. Mianserin 10(-8), 10( 7), 10(-6) and 10(-5) M had a similar inhibitory effect on responses to (-) noradrenaline. In the absence of neuronal uptake, the potentiating effect of mianserin on responses to field stimulation may be due to antagonism at presynaptic alpha-adrenoceptors. In the presence of 10(-6) M nortriptyline, 10( 5) M mianserin abolished responses to field stimulation.5 Following incubation of the tissue in the presence of 6-hydroxydopamine (10(-3) M for 3 h), mianserin (10(-7), 10(-6) and 10(-5) M) nortriptyline (10(-7) and 10(-6) M) and phentolamine (5 x 10(-8) and 5 x 10(-7) M) inhibited contractile responses to (-) noradrenaline. This illustrates the ability of these agents to inhibit the responses to noradrenaline at a postsynaptic site. The inhibitory effect was dose related with nortriptyline and phentolamine; this illustrates the ability of these agents to antagonize postsynaptic alpha-adrenoceptors. The inhibitory effect observed with mianserin was not dose-related. This suggests that in addition to its reported ability to antagonize postsynaptic alpha-adrenoceptors, mianserin may have another post-synaptic action at the level of, or distal to, the alpha-adrenoceptor.6 These results illustrate that, in the rat anococcygeus muscle, mianserin is a potent inhibitor of noradrenaline accumulation and may be an antagonist at presynaptic alpha-adrenoceptors. Mianserin also inhibits the responses to exogenously applied noradrenaline in this tissue by an action or actions at the level of, or distal to, the postsynaptic alpha-adrenoceptor. PMID- 6244038 TI - Influence of cellular transport on the interaction of amino acids with gamma aminobutyric acid (GABA)-receptors in the isolated olfactory cortex of the guinea pig. AB - 1 Freshly cut guniea-pig olfactory cortex slices contained 2.2 mmol gamma aminobutyric acid (GABA)/kg tissue weight. This declined during in vitro incubation at 25 degrees C in the absence of exogenous GABA, but increased to 6.95 mmol/kg after 1.5 h incubation in 1 mM GABA. 2 Uptake of [3H]-GABA (1 microM) was inhibited by 1 mM (+/-)-nipecotic acid (-83%), beta-amino-n-butyric acid (BABA) (-59%), L-2,4-diaminobutyric acid (DABA) (-63%), (+/-)cis-3 aminocyclohexane carboxylic acid (ACHC) (-53%), and 3-aminopropanesulphonic acid (3-APS) (-26%), but was increased by beta-alanine (BALA) (+23%). 3 Autoradiographs showed steep concentration gradients of radioactivity across slices incubated for short periods in [3H]-GABA. 4 Efflux of [3H]-GABA from pre loaded slices was accelerated strongly by nipecotic acid, BABA, DABA and ACHC but weakly or not all by BALA or 3-APS. 5 Nipecotic acid (1 mM) potentiated the surface-depolarization of the slice produced by GABA but not that produced by 3 APS. 6 The depolarizing actions of DABA, BABA, nipecotic acid and ACHC, but not that of 3-APS or BALA, were potentiated when the endogenous GABA content of slices was raised. 7 It is concluded that: (a) the depolarizing action of exogenous GABA is limited by cellular uptake; (b) surface-depolarizations produced by nipecotic acid, DABA, BABA and ACHC may be mediated by the release of GABA; and (c) neuronal, rather than glial, transport systems are responsible for these effects. PMID- 6244039 TI - Effects of hydralazine and verapamil on phosphorylase activity and guanosine cyclic 3',5'-monophosphate levels in guinea-pig taenia coli. AB - 1 The roles of guanosine cyclic 3',5'-monophosphate (cyclic GMP) and calcium in the relaxation produced by hydralazine and verapamil in potassium-depolarized guinea-pig taenia coli have been investigated.2 Depolarization of isolated strips of guinea-pig taenia coli by 124 mM KCl caused sustained contractures and increases in tissue levels of cyclic GMP.3 The KCl-induced increases in cyclic GMP levels appeared to be calcium dependent. No increases in cyclic GMP levels were seen in strips of taenia coli depolarized in the absence of calcium. Readdition of calcium to the depolarizing solution contracted the muscles and increased cyclic GMP levels. When calcium was removed from the depolarizing solution during the sustained, tonic phase of a KCl-induced contracture, both tension and cyclic GMP levels returned to control values.4 Administration of 50 muM verapamil to KCl-contracted muscles completely relaxed the muscles and caused cyclic GMP levels to return to control values within 14 min. Hydralazine, 2 mM, on the other hand, relaxed the depolarized muscles without lowering cyclic GMP levels. No significant changes in cyclic AMP levels were seen in any of these experiments.5 Similar results were obtained in an analogous series of experiments in which glycogen phosphorylase activity was measured instead of cyclic GMP levels. Activation of phosphorylase during contractions of guinea-pig taenia coli had previously been reported to be a calcium-dependent phenomenon.6 It was concluded that increases in tissue levels of cyclic GMP (or of cyclic AMP) were not responsible for the relaxant effects of hydralazine or verapamil in these experiments. It was also suggested, based on our results, that verapamil exerted its relaxant effects in the depolarized taenia coli by lowering cytoplasmic calcium levels, whereas hydralazine relaxed the depolarized muscles without lowering intracellular calcium activity. PMID- 6244041 TI - Synaptic connections of buccal mechanosensory neurons in the opisthobranch mollusc, Navanax inermis. AB - Mechanical stimulation of various areas of the pharyngeal wall and lips can produce EPSPs and IPSPs, as well as abruptly rising impulses, in primary sensory cells. IPSP fields are generally larger than EPSP fields and these fields are distributed without obvious order around fields from which afferent spikes are evoked. Apparently monosynaptic excitatory and inhibitory contacts are formed between primary sensory neurons. These synapses are blocked by high Mg2+ indicating chemical transmission. IPSPs are inverted by Cl- injection. Excitatory inputs can be electrically far from the soma. Sensory cells form apparently monosynsptic excitatory or inhibitory contacts on motoneurons mediating pharyngeal expansion. Brief sensory excitation can initiate sustained firing within this neuronal population and sustained synaptic activity in motoneurons. Interactions of sensory neurons may be important in information processing and in generating motor paterns. These neurons serve both primary sensory and interneuronal functions. PMID- 6244040 TI - Comparison of mianserin with desipramine, maprotiline and phentolamine on cardiac presynaptic and vascular postsynaptic alpha-adrenoceptors and noradrenaline reuptake in pithed normotensive rats. AB - 1 The cardiovascular effects of intravenous desipramine (0.03 and 0.1 mg/kg), maprotiline (0.5 mg/kg), mianserin (1.0 and 3.0 mg/kg) and phentolamine (0.25 mg/kg) were examined and compared in pithed rats. Several experimental procedures were used in order to distinguish between the effects of the compounds on cardiac presynaptic alpha-adrenoceptors and on neuronal noradrenaline reuptake, as inhibition of either mechanism produces an increase of neurotransmitter concentration within the sympathetic synapse and therefore results in a greater end organ response.2 Pressor responses elicited by noradrenaline were potentiated by desipramine and maprotiline, reduced by phentolamine and not significantly modified by mianserin. However, all four compounds inhibited the pressor action of tyramine. Furthermore, mianserin reduced the pressor response to adrenaline.3 Desipramine, maprotiline and mianserin, but not phentolamine enhanced the positive chronotropic effects of noradrenaline, without affecting those of isoprenaline.4 All four compounds abolished the clonidine-induced inhibition of heart rate responses to short term electrical stimulation of the spinal cord. Moreover, in rats with a persistent tachycardia (induced by continuous stimulation of the thoracic spinal cord) desipramine, maprotiline and mianserin further increased heart rate. This effect was also observed in animals pretreated with phentolamine, administered in order to inhibit cardiac presynaptic alpha adrenoceptors.5 In rats with a sustained tachycardia (100 beats/min produced by electrical stimulation of the spinal cord) both mianserin and phentolamine, in contrast to desipramine, shifted the clonidine heart rate dose-response curve to the right. Phentolamine was about 34 times more potent than mianserin in this respect.6 In pithed, reserpine-treated rats, the pressor responses to clonidine were not significantly modified by desipramine. The dose-response curves were shifted to the right by phentolamine (0.25 mg/kg) and mianserin (3.0 mg/kg).7 These results indicate that mianserin is an antagonist of both cardiac presynaptic and vascular postsynaptic alpha-adrenoceptors and also inhibits the neuronal reuptake of noradrenaline. PMID- 6244042 TI - The effects of intraocular injection of kainic acid on the synaptic organization of the goldfish retina. AB - Kainic acid (KA), an extended analog of L-glutamate, was injected into the eyes of living goldfish. After survival times ranging from 15 min to 6 days, retinae were inspected for KA-induced degeneration at both the LM and EM levels. KA had little effect on photoreceptors, mixed rod-cone bipolar cells, Muller cells, at least two types of amacrine cells and the optic nerve. Reversible edema was seen in both rod and cone horizontal cells. Pure cone bipolar cells and the majority of amacrine cells appeared to be destroyed by KA. The effect of KA is selective not only on the cell types involved, but also in the location of KA-induced edema on the affected cells, i.e., soma and proximal portions of dendrites of cone horizontal cells as opposed to the distal ends of dendrites of rod horizontal cells. Implications of these data are discussed in regard to the use of KA as a probe for glutamatergic pathways in the retina. One hypothesis suggested by our results is that rods use glutamate whereas cones use aspartate as their neurotransmitter. PMID- 6244043 TI - Cyclic AMP synthesis in guinea pig superior cervical ganglia: response to pharmacological and preganglionic physiological stimulation. PMID- 6244044 TI - Selective destruction by kainic acid of neurons innervated by putative glutamergic afferents in septum and nucleus of the diagonal band. PMID- 6244045 TI - The use of the transition elements manganese, cobalt and nickel as synaptic blocking agents on isolated, hemisected, mouse spinal cord. PMID- 6244046 TI - In vivo inactivation of quisqualate: studies in the cat spinal cord. PMID- 6244047 TI - Thy-1 cell surface antigen on cloned cell lines of the rat and mouse: stimulation by cAMP and by butyrate. AB - The level of the Thy-1 cell surface antigen on a number of established rat and mouse nerve cell lines can be stimulated by N6, O2'-dibutyryl adenosine 3':5' cyclic monophosphoric acid (Bt2cAMP), in some cases up to the antigen level found in whole brain. On rat cell line BN1010-3, stimulation is also produced by phosphodiesterase inhibitors, adenosine 3':5'-cycle monophosphoric acid (cAMP) and its 8-bromo derivative, and L-isoproterenol. Hence, antigen elevation appears to occur via cAMP-related metabolism. It is not a consequence of morphological changes brought about by cAMP elevation in these cells, and is apparently independent of the inhibition of cell division by the nucleotide. Elevations of intracellular cAMP levels for at least one hour are needed to produce Thy-1 stimulation, after which an enhanced level of Thy-1 is observable after about 12 h. Continuous stimulation is required to maintain elevated antigen levels, for upon removal of the stimulating agent, the level of Thy-1 returns to the original unstimulated value within 48 h. Potent stimulation of the antigen level is also obtained with butyrate at 1--2 mM, which appears to be acting by a cAMP independent mechanism. PMID- 6244048 TI - Modulation by GABA of cholinergic transmission in the striatum. PMID- 6244049 TI - GABAergic denervation of rat substantia nigra: functional and pharmacological properties. PMID- 6244050 TI - Changes in excitatory and inhibitory synaptic potentials leading to epileptogenic activity. AB - The effects of the epileptogenic agent, penicillin, on excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) were studied in the hippocampal in vitro slice preparation. The actions of penicillin were compared to those of bicuculline, an antagonist of gamma-aminobutyric acid. Neither substance enhanced monosynaptic EPSP amplitude in CA1 pyramidal cells, but both penicillin and bicuculline depressed IPSPs. Large depolarizations that gave rise to cellular bursting activity did develop after addition of penicillin or bicuculline to the bathing medium. There was also an increase in the incidence of fast prepotentials of 'd-spikes.' These observations are interpreted according to the hypothesis that penicillin and bicuculline block cellular IPSPs, and consequently allow remote intrinsic excitatory events to invade the cell soma and trigger action potentials. PMID- 6244052 TI - Local synaptic circuits in rat hippocampus: interactions between pyramidal cells. PMID- 6244051 TI - Identification and characterization of adrenergic receptors and catecholamine stimulated adenylate cyclase in hog pial membranes. AB - In order to define the adrenergic receptors in small pial blood vessels, we studied [3H]dihydroalprenolol (DHA) binding, [3H]dihydroergocryptine (DHE) binding, and catecholamine-stimulated adenylate cyclase in membranes prepared from the hog pia. [3H]dha bound to a saturable number of sites (0.09 pmol/mg protein) with a high affinity to (10 mM). The ability of a small series of adrenergic agents to compete for [3H]DHA binding was as expected for binding to beta-adrenergic membrane receptors. The receptor binding appeared to be composed largely of beta 2-adrenergic sites but some sites with beta 1 properties were detected. The beta-adrenergic agonist, isoproterenol, stimulated adenylate cyclase activity by 20% in pial membranes in the presence of GTP. The potency of catecholamines in stimulating adenylate cyclase correlated well with theif sites (0.39 pmol/mg) on these membranes. alpha-Adrenergic agents were potent competitors for [3H]DHE binding but dopamine, serotonin and histamine had effects only at high concentrations. These data demonstrate the presence of alpha- and beta-adrenergic membrane receptors and beta-adrenergically stimulated adenylate cyclase activity in small pial blood vessels from the hog. PMID- 6244053 TI - Long-term alterations of electrotonic synapses. PMID- 6244054 TI - A comparison of sodium-dependent glutamate binding with high-affinity glutamate uptake in rat striatum. AB - The specific sodium-dependent binding of [3H]glutamate to membranes of the rat striatum was examined and a comparison made with high affinity glutamate uptake. In the presence of sodium, [3H]glutamate binding was saturable and of high affinity. No binding could be detected in the absence of sodium. Removal of the cortical afferents to the striatum resulted in a parallel decrease in Na+ dependent glutamate binding and in high-affinity glutamate uptake. After the injection of the neurotoxin kainic acid into the striatum, the density of Na+ dependent glutamate binding sites was reduced by 40%, while high-affinity uptake showed no significant decrease. Drugs which inhibit high-affinity uptake were also effective at inhibiting Na+-dependent binding. The results suggest that about half the Na+-dependent glutamate binding sites in the striatum represent high-affinity uptake sites on the corticostriatal terminals. The remainder of the binding sites are located on striatal neurons and may also be uptake sites. PMID- 6244055 TI - Developmental changes in carbonic anhydrase and adenylate cyclase in quaking mice. AB - The present investigation focuses on the developmental changes in the activity and levels of carbonic anhydrase, adenylate cyclase and 3',5'-cyclic adenosine monophosphate (cAMP) in the Quaking mouse mutant in different regions of the brain. Carbonic anhydrase activity was found to be lower than normal in the forebrain of the C57/B Quaking mouse. The deficit in forebrain carbonic anhydrase was restricted to subcortical structures and was reflected equally in the membrane and soluble factions, indicating that neither pool was affected selectively. However, no difference in carbonic anhydrase activity was observed in purified myelin from Quaking and control mice. Investigation of the changes in carbonic anhydrase activity as a function of age showed a cessation in enzyme accumulation in Quaking mice at around 20 days postnatally, suggesting an abnormality in cellular development. A tritiated acetazolamide binding assay was used to quantitate the amount of enzyme present. The amount of carbonic anhydrase parallelled enzyme activity, suggesting that the defect in the Quaking animals was at the level of the control of enzyme synthesis. Similar studies on cyclic AMP metabolism showed a higher than normal adenylate cyclase activity in the upper brain stem region of Quaking mice of ages between 19 and 40 days. Adenylate cyclase activity was stimulated by norepinephrine in both control and Quaking animals. The increased adenylate cyclase activity in the Quaking mice was in contrast to a lower cyclic AMP level and could not be accounted for by an alteration in phosphodiesterase activity. PMID- 6244056 TI - On the role of calcium ions in the presynaptic alpha-receptor mediated inhibition of [3H]noradrenaline release from rat brain cortex synaptosomes. AB - Rat brain cortex synaptosomes, previously labeled by incubation with [3H]noradrenaline ([3H]NA) were continuously superfused with Krebs-Ringer media. Release of [3H]NA was induced by superfusion with medium containing either 15 mM K+, 20 microM veratrine or 1 microM of the calcium-ionophore A 23187 and was strongly dependent on the concentration of Ca2+ in the medium. Noradrenaline (1 microM, in the presence of the uptake inhibitor desipramine) inhibited K+-induced [3H]NA release by activation of presynaptic alpha-receptors. When the Ca2+ concentration in the medium was reduced, or the Mg2+-concentration increased, [3H]NA release appeared to be more susceptible to alpha-receptor mediated inhibition. Noradrenaline (1 microM) inhibited [3H]NA release induced by 15 mM K+, in the presence of 0.075 Ca2+ and 10 mM Mg2+, by 86%. Veratrine-induced release was also inhibited by alpha-receptor activation. However, [3H]NA release induced by the calcium-ionophore was not affected by alpha-receptor agonists. These results strongly support the view that alpha-receptor activation results in a decrease of the availability of Ca2+ for stimulus-secretion coupling processes. Presumably this is effected by an inhibition of voltage-sensitive calcium channels in the neuronal membrane associated with neurotransmitter release. PMID- 6244057 TI - Slow muscarinic depolarization in neurons of dissociated rat superior cervical ganglia can be evoked by iontophoresis of acetylcholine. PMID- 6244058 TI - Effect of the GABA receptor agonist muscimol on regional cerebral blood flow in the rat. PMID- 6244059 TI - Determination of dopamine in the anterior pituitary as an index of tuberoinfundibular dopaminergic function. PMID- 6244060 TI - GTP modulation of opiate receptors in regions of rat brain and possible mechanism of GTP action. PMID- 6244061 TI - Enzymes of phospholipid synthesis: axonal versus Schwann cell distribution. AB - Using quantitative EM autoradiography to localize sites of incorporation of tritiated inositol and choline into mouse sciatic nerve, we observed a substantial axon-based phosphatidylinositol synthesis, but no axonal phosphatidylcholine synthesis. In the present communication we provide biochemical evidence for the axonal transport of CDP-diglyceride:inositol transferase (EC 2.7.8.11), the terminal enzyme in de novo phosphatidylinositol biosynthesis. Axonal transport of 1,2-diacyl-glycerol:CDP-choline choline phosphotransferase (EC 2.7.8.2), required for de novo phosphatidylcholine synthesis, was not apparent in these studies. During subcellular fractionation activities for the synthesis of phosphatidylinositol by inositol transferase (IT) and phosphatidylcholine by choline phosphotransferase (CPT) were recovered in crude microsomal fraction of rat sciatic nerve. However, CPT was much more highly enriched in the microsome fraction than IT, which may be an indication of the different subcellular localizations of these enzymes. Following ligation, we detected localized increases in the activities of both enzymes in 5 (and 3) mm segments taken immediately proximal and distal to the ligature. Both activities increased in a linear fashion in the proximal segments over the ensuing 72 h period. It took about 40 h (IT) and 56 h (CPT) for the activities in the segments proximal to the ligature to double compared to unligated contralateral (control) nerves. The time-dependent accumulation of IT was primarily due to axonal transport, while that of CPT was largely a result of increased enzyme activity in local Schwann cells. Evidence came from double ligation studies, where a proximal ligature, acting to restrict orthograde axonal transport, reduced accumulation in a distal ligature by 80% for IT, but only 28% for CPT. Conversely, blockage of the Schwann cell response with actinomycin D, reduced accumulation of CPT by 83% and IT by only 36%. Finally, light microscopic autoradiography was used to show that in the segment proximal to the ligature, tritiated inositol incorporation into lipid was primarily axonal, whereas that of tritiated choline remained primarily associated with Schwann cells. PMID- 6244062 TI - Radioautographic localization of specific binding sites for blood-borne angiotensin II in the rat brain. PMID- 6244063 TI - Guanyl nucleotide interactions with opiate receptors in guinea pig brain and ileum. PMID- 6244064 TI - Electrophysiologic evidence that retinotectal synaptic transmission in the goldfish is nicotinic cholinergic. AB - A previous study identified, by conduction velocity following optic nerve shock, 3 classes of retinal fibers which project to 3 distinct laminae of the goldfish optic tectum. In the present study, the effect of various pharmacological agents on the synaptic efficacy of each of the 3 classes of retinal fibers was assessed by the use of current source-density analysis. All 3 classes of optic fibers appear to be nicotinic cholinergic. Six different nicotinic antagonists were tested. All 6 were effective in decrementing the responses of all 3 classes to a criterion level: alpha-bungarotoxin (10-8 M), alloferin (10-5 M), curare (10-4 M), metocurine (10-4 M), hexamethonium (10-4 M) and gallamine (10-3 M). Atropine, a muscarinic antagonist, had only a slight effect even at 10-3 M. Five nicotinic agonists tested also decremented synaptic responses: nicotine (10-5 M), carbamylcholine (10-4 M), acetylcholine (10-4 M), succinyl choline (10-4 M) and decamethonium (10-3 M), presumably via cellular depolarization and receptor desensitization. Two inhibitors of acetylcholinesterase prolonged the response at 10-4 M and decremented it as well at 10-3 M. Hemicholinium 3, an inhibitor of the high affinity uptake of choline, produced a gradual activity-dependent decrement in the responses. Beta-bungarotoxin, a presynaptically-acting toxin, abolished not only the postsynaptic components but also the presynaptic components at 10-6 M. In all other cases the presynaptic deflections were generally unaffected, and with the exception of the toxins, a return to at least 90% of the control value was achieved. In contrast, GABA (10-3 M) and bicuculine (10-4 M) both produced no discernible effect on the 3 classes of responses, and glutamate (10-3 M) produced only a slight decrement, which probably represents a non-specific effect. PMID- 6244065 TI - Modulation of rat brain alpha- and beta-adrenergic receptor populations by lesion of the dorsal noradrenergic bundle. AB - Bilateral lesion of the ascending noradrenergic fibers in the dorsal bundle of adult Wistar rats with 4 micrograms 6-hydroxydopamine caused extensive depletion of norepinephrine in all forebrain areas, but led to a 54% increase in norepinephrine levels in the cerebellum. beta-Adrenergic receptor binding of [3H]dihydroalprenolol was significantly increased in all forebrain areas depleted of norepinephrine except hypothalamus. The increase in [3H]dihydroalprenolol binding was due to 62% and 34% increases in the number of beta-receptor sites in the frontal cerebral cortex and hippocampus respectively. Binding of [3H]WB-4101 to alpha 1-adrenergic receptors after dorsal bundle lesion was augmented generally to a lesser extent than beta-receptor binding, with significantly increased numbers of sites only in the frontal cortex (74%), thalamus (20%) and septum. Both alpha 1- and beta-receptor binding sites were reduced in number by 25-28% in the cerebellum of dorsal bundle-lesioned rats, whereas intraventricular administration of 6-hydroxydopamine to adult rats, which depletes norepinephrine in the cerebellum by 96%, increased cerebellar alpha 1- and beta-receptor binding by 33-40%. Binding of [3H]clonidine to forebrain alpha 2-adrenergic receptors was significantly elevated in the frontal cortex, but reduced in the amygdala and septum, after dorsal bundle lesion. PMID- 6244066 TI - Taurine release from the pineal-gland is stimulated via a beta-adrenergic mechanism. AB - Pineal glands were prelabeled in organ culture with [14C]taurine, and then treated with biogenic amines. The rate of release of [14C]taurine was rapidly elevated by low concentrations of norepinephrine, apparently acting through a beta-adrenergic mechanism. The release was probably not due to a nonspecific change in membrane permeability, as a comparable release was not seen with [14C]glycine and [14C]alpha-aminoisobutyric acid. These findings suggest that the release of taurine may be related to or a reflection of the early events in adrenergic activation of the pineal gland, such as hyperpolarization of pinealocytes. The released taurine might also have an extracellular role as it has been recently shown that extracellular taurine can interact with pineal beta adrenergic receptors to stimulate melatonin production. Thus, the released taurine could possibly act as an extracellular feedback messenger. PMID- 6244067 TI - Axonal site for impulse initiation and rhythmogenesis in Aplysia pacemaker neurons. PMID- 6244068 TI - Evidence for a direct spinal mechanism in morphine-induced inhibition of nociceptive reflexes in humans. PMID- 6244069 TI - Alpha-adrenoceptor and dopamine receptor antagonists do not block the slow inhibitory postsynaptic potential in sympathetic ganglia. PMID- 6244070 TI - Prolonged depression of spinal transmission of nociceptive information by 5-HT administered in the substantia gelatinosa: antagonism by methysergide. PMID- 6244071 TI - [Adenine nucleotides and (Na+ + K+)ATPase as a possible criterion of viability of hypothermically preserved dog kidneys]. PMID- 6244072 TI - Carcinoma of major salivary glands. AB - Ninety-four patients with carcinoma of the major salivary glands seen at Indiana University Hospitals from 1960-1977 were studied. Eighty-four patients completed their planned course of therapy, and 49 of 84 patients remain alive with no evidence of disease 2-17 years following treatment. Comparison has been made for three modalities: surgery alone, radiation therapy alone, and a combined approach. Surgery alone was used for treatment of early lesions, and 22 of 38 patients (58%) remain free of disease. Radiation therapy alone was used for advanced cases and palliation, and 6 of 16 patients (37.5%) remain free of disease. In the combination treatment, 21 of 30 patients (70%) are alive and free of disease. In the combination treatment, 21 of 30 patients (70%) are alive and free of disease from 2-17 years after treatment. Ten patients did not complete treatment and all of these patients died of disease. PMID- 6244073 TI - The role of curative radiotherapy in the treatment of lung cancer. AB - From 1963-1974, 141 patients with lung cancer were treated with curative intent in the A. Maxwell Evans Clinic in Vancouver. The clinical presentation, age and sex distribution, histology, and reasons for surgery not being carried out are examined. The results of this treatment are presented. An attempt has been made to isolate a group of patients who have a better prognosis so that treatment selection can be improved. Hemoptysis, cough, dyspnea, and incidental finding on routine chest x-ray were the most common manner of presentation. Thirty-four percent of the patients were over 70 years of age and 13% were women. The crude overall three- and five-year survival rates were 18 and 10% (19 and 9% in the men, 17 and 14% in the women). Patients presenting with dyspnea had a better survival than those presenting with cough and hemoptysis. Patients with lesions less than 3 cm in diameter had a 28% three-year survival, compared with 14% for lesions greater than 5 cm in diameter. The three- and five-year survival rates in patients over 70 years of age were 23 and 17% respectively. The response to treatment and the survival was better in the patients with squamous cell carcinoma. Twenty-two percent were alive at three years and 12% at five years as compared with 9 and 5% for other histologies. Fifty-four percent of the 35 patients with a complete response and with squamous cell carcinoma were alive at three years, compared with only 8% of the 12 patients with other histologies who showed a complete response. PMID- 6244074 TI - Iodine-125 implant and external beam irradiation in patients with localized pancreatic carcinoma: a comparative study to surgical resection. AB - Twelve patients with biopsy-proven clinically localized ductal pancreatic cancers (less than 7 cm in greatest diameter) judged unsuitable for resection were treated by bypass surgery, an Iodine-125 implant (20-39 mCi), and postoperative irradiation (4000-4500 rads). The potential problems of significant bleeding, pancreatic fistula, or pancreatitis were not experienced. A local recurrence developed in one patient and two recurred in regional lymph nodes. The projected median survival of the group is 11 months with four of the 12 patients still surviving. For purposes of comparison all patients with pancreatic ductal carcinoma treated by radical resection during a similar time were evaluated. All ten have died with a median survival of six months. Twelve of 22 (55%) of the combined implanted and resected groups have developed distant metastasis. Further pursuit of intraoperative techniques of irradiation in combination with adjuvant multidrug chemotherapy seems indicated in an attempt to prolong patient survival which is now limited by hematogenous metastases. PMID- 6244075 TI - 5'-Nucleotide phosphodiesterase isozyme-V in health, in cancer, and in viral hepatitis. AB - An abnormal, fast-moving 5'-nucleotide phosphodiesterase isozyme was found in 90.0% of 20 Malaysian patients with primary hepatoma and in 23.5% of 391 Malaysian patients with various malignant diseases; it was also discovered in 42.9% of 14 Malaysian and American patients with clinically active hepatitis B infection; in 16.7% of 18 healthy American blood bank donors who were positive for hepatitis B surface antigen (HBsAg); in 13.9% of 287 healthy Malaysian blood bank donors, some positive for HBsAg; and in none of 160 healthy American donors who were negative for HBsAg. A correlation of this abnormal isozyme with hepatoma and with infectious hepatitis B is clearly evident. PMID- 6244076 TI - The effects of long-term ingestion of asbestos on the colon of F344 rats. AB - Weanling F344 rats, which were fed a diet containing 10% chrysotile (B), were studied over their life-time to determine the effects of ingested asbestos on the colon. Control groups consisted of rats fed a diet containing a 10% nonnutritive cellulose or a standard laboratory rat diet. The pathological findings in the colons of 501 rats (189 on asbestos diet, 197 on fiber control diet, and 115 on standard control diet), are reported here. Epithelial tumors of the colon (eight adenocarcinomas and one adenoma) were found in nine of the rats on study. Four of the tumors were in asbestos-fed rats, two tumors were found in the non-nutritive cellulose controls, and three tumors were found in the standard laboratory rat diet controls. The probability (based on actuarial analysis) of developing adenoma or adenocarcinomas during the 32 months of the study were 7.4% for the asbestos-fed group, 3.5% for the fiber control diet and 4.0% on the standard control diet. In addition, one malignant mesothelioma of the type induced by intraperitoneally administered asbestos was found in the asbestos-fed group. Non neoplastic lesions of the colon were also evaluated. The cumulative risk for development of any colon-associated lesion (non-neoplastic plus neoplastic lesions) was greatest for asbestos-fed rats (17.9%), compared to 13.6% for those fed the fiber control diet and 8.2% for those fed the standard control diet. The colon tissue levels of adenosine, 3'-5'-cyclic monophosphate (cAMP) were significantly lower in the animals fed asbestos compared to the control diets. Chrysotile fibers were seen by electronmicroscopy (e.m.) in six of ten ashed colon specimens of rats fed the asbestos diet. Although the differences in numbers of tumors between the animals fed asbestos and the controls were not statistically significant at the 5% level, we felt that the combination of observations including 1) evidence of increased probability of asbestos-fed animals to develop colon lesions in general; 2) evidence of a special type of mesothelioma in rats fed asbestos; 3) evidence for a cell regulator defect (lowered cAMP levels) in colon tissues of animals fed asbestos; and 4) evidence for asbestos fiber penetration of the colonic mucosa (e.m. studies) suggest that ingested asbestos is not inert in the colon. PMID- 6244077 TI - Human skin fibroblasts from individuals genetically predisposed to cancer are sensitive to an SV40-induced T antigen display and transformation. AB - In the present study we have used a viral probe to determine the genetic susceptibility of fibroblastic cell strains derived from individuals with hereditary adenomatosis of the colon and rectum (ACR), an autosomal dominant trait. This report shows an increased sensitivity of apparently karyologically normal diploid skin fibroblasts from ACR individuals to an SV40-induced T antigen display and transformation. None of the SV40-transformed cells grew as tumors in athymic mice and they all appeared to have a finite life span. The results suggest that the induction of T antigen positive cells by SV40 may be used as a marker of cancer risk in this cell system. PMID- 6244078 TI - Biochemical, molecular, and pharmacologic approaches to large bowel cancer: an overview. AB - The role of the nucleolus in the control of cell proliferation in mammalian cells is becoming increasingly clear. Our expanding knowledge of the cellular and molecular mechanisms that regulate cell division in normal and cancerous cells opens new possibilities for improving the diagnosis, prognosis, and therapy of tumors. PMID- 6244079 TI - CCNU-chemotherapy of hemispheric supratentorial glioblastoma multiforme. AB - One hundred and three patients with hemispheric supratentorial glioblastoma multiforme were studied. All patients were operated on and a histologic diagnosis of glioblastoma multiforme was made. Patients were randomly placed in one of three treatment schedules within 3 weeks of surgery: Group A: combined radiation therapy and drug (CCNU) therapy (26 cases); Group B: CCNU given orally every 6-8 weeks (27 cases); Group C: standard radiation therapy alone (50 cases). All patients were periodically controlled by clinical and instrumental (EEG, scan, EMG, CAT) evaluations; laboratory data examinations were also frequently performed. The treatment results have been evaluated according to length of survival, social quality of life, and positive or negative response to chemotherapy. In our opinion the clinical findings are interesting but the statistical results are somewhat negative, especially when the groups of patients are not homogeneous. PMID- 6244080 TI - A human liposarcoma cell line producing hyaluronic acid. AB - A human liposarcoma cell line COLO 222, derived from a primary tumor in a 62-year old male, elaborates hyaluronic acid. COLO 222 is characterized on the basis of histochemical, ultramorphological, and cytogenetic properties, along with isozyme phenotype and cell products. A chromosome mode of 53 predominates and unique Giemsa-banded marker chromosomes are identified. An autochthonous lymphoid cell line, COLO 143v, was established after the addition of exogenous Epstein-Barr virus. Cytogenetic analysis of Colo 143v is consistent with a normal male karyotype. COLO 143v possesses B-cell characteristics. This autochthonous system had been used for immunological studies and cytotoxicity assays. PMID- 6244081 TI - Postirradiation sarcoma (malignant fibrous histiocytoma) following breast carcinoma: an ultrastructural study of a case. AB - Sarcoma of the chest wall following postoperative radiation therapy (2500 rads) for breast carcinoma is presented; it appeared 16 years after the initial radiation, and had light and electron microscopic features of malignant fibrous histiocytoma (MFH). Unique ultrastructural finding was the presence of Langerham cell granules in some of the tumor cells. This appears to be the first documented instance of a soft tissue MFH containing such granules in the tumor cells. PMID- 6244082 TI - Hormonal polypeptides and amine metabolites in small cell carcinoma of the lung, with special reference to stage and subtypes. AB - To elucidate the ectopic hormonal pattern in patients with small cell carcinoma of the lung, plasma ACTH, serum calcitonin, serum gastrin, plasma glucagon, serum insulin, plasma secretin, plasma VIP, serum growth hormone, serum hCG/LH, the total of serum hCG and hCG-beta-subunit,serum alpha-subunit, serum human placental lactogen, urine ADH, urine 5-HIAA, urine VMA, urine HVA, and urine hCG LH were measured prior to therapy in 75 patients. Twenty-two patients (29%) had elevated plasma ACTH, and 18 of these had concomitant increased values of corticosteroid in a 24-hour urine sample. Forty-eight patients (64%) were found to have elevated serum calcitonin, and one-third of the patients were diagnosed as having the ectopic ADH syndrome. Serum gastrin concentrations were increased in 20% of the patients, but the elevations were marginal in almost all cases. None of the remaining substances was found to be significantly elevated. Concentrations of plasma ACTH, serum calcitonin, and urine ADH were not found to be correlated with the stage of the disease, and no correlation of these substances with the histological subtypes of small cell carcinoma was disclosed. PMID- 6244083 TI - Assessment of biochemical tests for bone and liver involvement in malignant lymphoma patients. AB - A profile of biochemical tests was performed on 72 patients attending a lymphoma clinic. Urinary hydroxyproline excretion was increased in 24 cases at the outset; of these ten had positive clinical or radiological evidence of bone disease at that time, and in a further ten such evidence became available over the next two years. Hepatic involvement was detected among 9 patients at the initial examination. All of these, and a further five who developed liver involvement over the next two-year period had raised activity of serum 5'-nucleotidase. Total serum alkaline phosphatase was raised in 8 of the 9 patients with initial involvement, but only 1 of the 11 patients who subsequently developed hepatic disease; the heat stability test indicated the presence of the hepatic isoenzyme in these cases. Alkaline phosphatase was raised in 10 of the 20 cases with initial or subsequent evidence of bone disease, heat stability indicating the bone isoenzyme to be predominant. Serum ornithine transcarbamoylase was raised in only 7 patients with initial hepatic involvement, and the aminotransferases were not helpful in identifying lymphomatous involvement of the liver. PMID- 6244084 TI - Association of Kaposi's sarcoma with second primary malignancies: possible etiopathogenic implications. AB - The association of Kaposi's sarcoma (KS) with second primary cancers, especially of the lymphoreticular system, has been frequently noted. To confirm these reports in a systematic way, data on a series of 92 patients with KS treated at Memorial Sloan-Kettering Cancer Center (MSKCC) 2949-1975 were subjected to extensive statistical analysis. Use was made also 4517 double primaries including all sites, diagnosed at MSKCC 1949-1974, and 1959 simultaneous double primaries from the Third National Cancer Survey. Some key results: (1) of KS patients had toher primary malignancies; (2) there was a 20-fold increase in the incidence of lymphoreticular malignancies after diagnosis of KS; (3) in the MSKCC series double primaries, lymphoreticular malignancies were involved in 8% of cases; for KS alone the corresponding figure was 58%. Our findings provide evidence in support of possible etiopathogenic mechanisms that may be involved in the natural course of KS. PMID- 6244086 TI - Adenoid cystic carcinoma of the esophagus: a light and electron microscopic study. AB - The light and electron microscopic appearances of adenoid cystic carcinoma of the esophagus are presented. Typical light microscopic features of adenoid cystic carcinoma were seen, but a unique additional feature was the presence at one edge of the tumor of gland-like structures lined entirely by tumor cells and opening onto an intact esophageal epithelium. Electron microscopy showed cystic spaces containing replicated basement membrane surrounded by epithelial cells with occasional myoepithelial cells at the interface. Rare lumina were seen between the cells with microvilli projecting into them. Occasional epithelial cells contained granules of neurosecretory tape. Both the light and electron microscopic findings strongly support an origin from the intercalated duct of esophageal mucus glands. The paucity of gland lumina may represent a lesser degree of differentiation which would accord well with the known biological aggressiveness of the tumor at this site. PMID- 6244085 TI - Prognostic factors in Burkitt's lymphoma: importance of total tumor burden. AB - In 42 patients with African Burkitt's lymphoma, we have studied biochemical and clinical correlations with prognosis. Clinical stage and anti-EA titer were the best predictive factors, but lactic dehydrogenase (LDH) and uric acid (UA) concentrations also correlated with stage and prognosis, whereas lactic acid (LA), which was significantly elevated in Stage D, did not significantly correlated with prognosis or with LDH and UA levels. All of these factors with the possible exception of LA reflect the total body burden of tumor. We conclude that the tumor burden is the single most important prognostic factor in Burkitt's lymphoma, and that this is reflected directly by LDH and UA concentrations, and probably indirectly by anti-EA titer. PMID- 6244087 TI - Production of spleen focus-forming virus and murine leukemia virus by early erythroblasts after Friend virus infection. PMID- 6244088 TI - Effects of cyclic nucleotides and prostaglandins on normal and abnormal human myeloid progenitor proliferation. PMID- 6244089 TI - Activities of some enzymes of pyrimidine and DNA synthesis in a rat transplantable hepatoma and human primary hepatomas, in cell lines derived from these tissues, and in human fetal liver. AB - Activites of the enzymes DNA polymerase, thymidine kinase, thymidylate kinase, thymidylate synthase, and deoxycytidylate deaminase have been measured in rat and human normal and neoplastic liver, in human fetal liver, and in cell lines derived from human hepatomas and rat transplantable hepatomas. The activities of these enzymes were increased in rat transplantable hepatomas, relative to rat normal or host liver, to a degree corresponding to the rapid growth rate of these tumors. With the exception of thymidine kinase, which did not change, the activities of these enzymes increased in human hepatomas relative to the corresponding host liver (apparently normal liver tissue from the same patient) and to human normal liver. The increases in enzyme activity observed in human hepatomas were small in comparison with those found in the rapidly growing rat hepatomas. The activities of deoxycytidylate deaminase in both human and rat liver tissues were 2 to 3 orders of magnitude higher than those of the other enzymes assayed. Activities of the enzymes of DNA synthesis in a slow-growing cell line derived from a human hepatoma were similar to those in human hepatoma tissues. In the case of rapidly growing cell lines derived from rat and human hepatomas, enzyme activities were higher than those in the corresponding tissues. PMID- 6244090 TI - Clinical pharmacokinetics of adriamycin in hepatoma patients with cirrhosis. PMID- 6244091 TI - Properties of a calcitonin receptor and adenylate cyclase in BEN cells, a human cancer cell line. AB - A human lung cancer cell line (BEN cells) was found to have a calcitonin responsive adenylate cyclase. Various calcitonins and synthetic analogs stimulated adenylate cyclase activity withe same relative potency as they show in lowering blood calcium in the rat. Preincubation of the cells with calcitonin, followed by washing, led to loss of subsequent adenylate cyclase response to hormone. This was a dose-dependent phenomenon. The binding of [125I]salmon calcitonin to freshly subcultured cells was studied. The ability of calcitonins and analogs to compete for binding paralleled their efficacies in stimulating adenylate cyclase. Binding was saturable, reversible, and consisted of a single class of noninteracting sites with a mean Kd of 10.75 X 10(-10) M, K of 0.93 X 10(9)/M, and mean receptor number of 2.71 X 10(4)/cell. It is not known whether the calcitonin receptor is inappropriate to the cell of origin of the tumor. The BEN cells provide a means of isolating and studying the properties of the calcitonin receptor and of evaluating the significance for the tumor of a hormone responsive adenylate cyclase. PMID- 6244092 TI - Cell surface adenosine 5'-triphosphatase as an in vitro marker of the lineage and cytodifferentiation of oncogenic epithelial cells from rat liver parenchyma. AB - The relationship between the oncogenicity and the surface properties of cultured liver epithelial cells has been studied with the newborn Wistar rat-derived euploid line, RL34, and its heteroploid variants. An oncogenic variant, RL34HT, appeared to be more functionally active than its nononcogenic counterparts with respect to cell surface adenosine 5'-triphosphatase (ecto-ATPase) as well as to cytoplasmic enzymes such as tyrosine aminotransferase, gamma-glutamyl transpeptidase, and alkaline phosphatase. The cell surface of RL34HT was distinguished from those of nononcogenic and marginally oncogenic cell populations by the presence of abundant microvilli and by the absence of large external transformation-sensitive protein (fibronectin). High-Km and high-Vmax Ca2+-Mg2+ -ecto-ATPase was found in RL34HT. All nononcogenic cell lines had a flat granular surface membrane with high levels of fibronectin and also exhibited ecto-ATPase activity with low Km and low Vmax. When RL34HT was grown in dibutyryl cyclic adenosine 3',5'-monophosphate and theophylline, the external cell surface was partially restored to the polypeptide compositions of RL34, and there was an increase in Vmax of ecto-ATPase without a change in Km. The high-Km ecto-ATPase may be a useful indicator reflecting the lineage and cytodifferentiation of oncogenic liver epithelial cells, since it is also known to be localized at the bile canalicular microvilli of normal adult hepatocytes. PMID- 6244093 TI - Effect of liposome-encapsulated quercetin on DNA synthesis, lactate production, and cyclic adenosine 3':5'-monophosphate level in Ehrlich ascites tumor cells. AB - Quercetin (3,3',4',5,7-pentahydroxyflavone) entrapped within phospholipid vesicles inhibited [3H]thymidine incorporation and lactate production in Ehrlich ascites tumor cells. The presence of serum proteins in concentrations of up to 40 mg/ml did not alter the extent of the inhibitory effect of the liposome-entrapped flavone. At the same concentrations, serum proteins eliminated almost completely the inhibitory effects of the free quercetin on these metabolic processes. Prolonged sonication and different lipid compositions of the liposomes did not increase the inhibition of [3H]thymidine incorporation by the entrapped quercetin in the presence of serum albumin. On the other hand, serum albumin eliminated the elevation of the cyclic adenosine 3':5'-monophosphate level in these cells produced by both free and liposome-entrapped flavone. Attachment between Ehrlich ascites tumor cells and quercetin-loaded liposomes is demonstrated in negatively stained electron micrographs. The liposomes ranged in size from 50 to 100 nm. After 10 min of incubation, these liposomes were distributed randomly on the cell surface at distances of 100 to 200 nm. PMID- 6244094 TI - Reflector cells in the skin of Octopus dofleini. AB - The cells that form the reflecting layer beneath the chromatophore organs of the octopus are conspicuous elements of its dermal chromatic system. Each flattened, ellipsoidal reflector cell in this layer bears thousands of peripherally radiating, discoidal, reflecting lamellae. Each lamella consists of a proteinaceous reflecting platelet enveloped by the plasmalemma. The lamellae average 90 nm in thickness and have variable diameters with a maximum of about 1.7 micrometer. Sets of reflecting lamellae are organized into functional units called reflectosomes. The lamellae in each reflectosome form a parallel array - similar to a stack of coins. The average number of lamellae in a reflectosome is 11. Adjacent lamellae are uniformly separated by an extracellular gap of about 60 nm in embedded specimens. The reflectosomes are randomly disposed over the surface of the reflector cell. The observed organization of the reflectosomes is compatible with its role as a quarter-wave thin-film interference device. The alternating reflecting lamellae and intelamellar spaces constitute layers of high and low refractive indices. Using measurements of the thicknesses and refractive indices of the platelets and interlamellar spaces, we have calculated that the color of reflected light should be blue - green, as seen in vivo. The sequence of events leading to the definitive arrangement of the reflectosomes is uncertain. The reflector cells of O. dofleini are compared and contrasted with the iridophores of squid. PMID- 6244095 TI - Bacilliform inclusions in cells of the proximal pars distalis in the pituitary of four species of Tilapia (Teleostei). AB - Thin sections and replicas of freeze-etched pituitaries from six species of the teleostean family of Cichlidae were studied by electron microscopy. Four species belonging to the genus Tilapia exhibit rod-like structures, i.e., "bacilliform inclusions" (BI), about 1-2 micrometer in length in cells of the proximal pars distalis. The BI are found either isolated or fused in small groups. They are enclosed in an envelope similar to that of secretory granules. Both the BI and the secretory granules give a positive PAS-reaction. PMID- 6244096 TI - Evidence that lipolytic peptide B occurs in the ACTH/MSH-cells of the pituitary and in the brain. An immunocytochemical study of its distribution in correlation to the distribution of neurophysin. AB - Several lipid-mobilizing peptides occur in the pituitary, among them beta lipotropin and "lipolytic peptide A and peptide B". The latter two peptides are distinct from beta-lipotropin and appear to be chemically related to the neurophysins. Immunohistochemistry has now revealed that the lipolytic peptide B of the pituitary is localized in the ACTH- and MSH-cells. In addition, immunoreactive peptide B was found in axons of the posterior lobe of the pituitary. Immunoreactive peptide B was found also in nerve fibers and nerve cell bodies in the hypothalamus, particularly in the hypothalamo-hypophyseal tract and in the magnocellular neuronal system. Immunoreactive nerve fibers were numerous also in the periventricular nucleus of the thalamus. The antiserum against peptide B cross-reacts with neurophysin I, and hence, it cannot be excluded that at least part of the immunostaining in the brain reflects the presence of the latter component. However, the regional distribution of immunoreactive peptide B and neurophysin was not identical. Therefore, it is possible that authentic peptide B occurs not only in the pituitary but also in the brain. PMID- 6244097 TI - Evidence for hemocyanin formation in the compound eye of Squilla mantis (Crustacea, Stomatopoda). AB - In the retina and in the subretinal space of the compound eye of Squilla mantis a special kind of pigment cell is present. The crystalline inclusions of this cell have been identified as hemocyanin, as determined (i) by the dimensional congruence of the crystalline substructure with the dimensions of isolated, purified hemocyanin, and (ii) by the immunofluorescence reaction using anti hemicyanin antibodies. The ultrastructure of these cells, their location and the presence of crystalline bodies in their cytoplasm suggest that they are sites of hemocyanin synthesis and homologous to the cyanocytes or cyanoblasts of Limulus. PMID- 6244098 TI - A DNA segment from D. melanogaster which contains five tandemly repeating units homologous to the major rDNA insertion. AB - We describe a cloned segment of D. melanogaster DNA (cDm219) that contains five tandemly arranged sequence units homologous to the type I insertion sequence found in the majority of 28S rRNA genes on the X chromosome. Heteroduplex studies show that two of the units have a deletion corresponding to a 1.1 kb piece of DNA close to the right-hand end of the type I insertion. Another unit has a 7.5 kb sequence (zeta) substituted for a 0.95 kb piece of DNA close to the left-hand part of the type I rDNA insertion. The two remaining units are interrupted by the Col E1 plasmid vector. There are also differences in the restriction endonuclease cleavage maps both between the units of cDm219 themselves and compared to the restriction endonuclease cleavage maps of cloned rDNA segments that contain type I insertions. Quantitation of the gel transfer hybridization of zeta element probes to restriction endonuclease digests of D. melanogaster DNA indicates there are 30--40 copies of zeta sequences distributed in seven major arrangements within the haploid genome. The hybridization of zeta and insertion sequence probes to a library of D. melanogaster DNA segments cloned in bacteriophage lambda indicates at least 4--6 copies of the zeta element could be linked to insertion sequences. The common site of in situ hybridization of zeta sequences is to the chromocentral heterochromatin of polytene chromosomes. PMID- 6244099 TI - Multiple actin-related sequences in the Drosophila melanogaster genome. AB - In this paper we describe the isolation and characterization of a 7.2 kb D. melanogaster chromosomal DNA fragment (K1) which contains nucleotide sequences complementary to D. melanogaster actin mRNA. Plasmid K1 was identified using a Dictyostelium actin cDNA plasmid, B1, as a probe. D. melanogaster mRNA selected by hybridization with immobilized K1 DNA was translated in vitro to yield products which co-migrate with the D. melanogaster actins I, II and III in two dimensional gel electrophoresis and bind to DNAase I agarose. A physical map localizing restriction endonuclease cleavage sites in the K1 DNA fragment and the direction of transcription is presented. The position of the coding region has been localized by hybridization with labeled B1 DNA and with labeled poly(A) containing D. melanogaster RNA. On the basis of hybridization of labeled subfragments of plasmid K1 to restriction endonuclease-cleaved D. melanogaster embryo DNA, we conclude that the nucleotide sequence of the presumptive coding region is responsible for labeling of a pattern of multiple restriction fragments from embryo DNA. The chromosomal locus from which DNA fragment K1 is derived has been localized by in situ hybridization to two closely linked bands in the region 88F. Related DNA sequences corresponding to putative actin genes have also been mapped cytologically. These results support the hypothesis that the genes for actin in D. melanogaster are members of a closely related family of coding sequences. PMID- 6244100 TI - Translocation specificity of the Tn3 element: characterization of sites of multiple insertions. AB - 247 independent events involving insertion of the TN3 transposable element into a 4 kb constructed plasmid (pTU4) of partially known DNA sequence were studied by restriction endonuclease mapping, and 65 of these insertion sites were examined further by DNA sequence analysis. Our results show that the previously proposed regional specificity for Tn3 insertion is associated with a strong preference for AT-rich segments as insertion sites. Moreover, multiple insertions of the Tn3 occurred at certain AT-rich nucleotide positions, and 23 of 26 independent insertion events at a single nucleotide position were found to be in the same orientation. A region of the recipient plasmid showing major homology with the terminal 18 bp of Tn3 was identified in the vicinity of an 11 nucleotide segment that included three insertional hot spots and 36 independent insertions. Our results indicate that the site and orientation of insertion of Tn3 are at least partly determined by the primary nucleotide sequence of the recipient genome, and suggest that insertional hot spots may result from the combined effects of AT richness plus homology of the recipient genome with the terminal sequences of Tn3. PMID- 6244101 TI - Specific incorporation of host cell surface proteins into budding vesicular stomatitis virus particles. PMID- 6244102 TI - Phenotypic alteration in retroviral gene expression by leukemia-resistant thymocytes differentiating in leukemia-susceptible recipients. AB - (AKR x NZB)F1 mice possess the dominant genes, Akv-1, Akv-2, Nzv-1a and Nzv-2a, which determine the expression of ecotropic and xenotropic viruses. Nevertheless, their thymic lymphocytes fail to produce these agents, and these mice are resistant to leukemia. We investigated the mechanism of this cell-specific restriction in radiation chimeras. (AKR x NZB)F1 thymocytes that had differentiated in lethally irradiated AKR recipients produced high levels of ecotropic and xenotropic viruses and showed marked amplification of MuLV antigen expression. Polytropic viruses could also be isolated from such thymocytes. These virological changes in chimeric thymocytes were donor- and host-specific and occurred only when (AKR x NZB)F1 bone marrow cells were inoculated into AKR recipients. This inductive capacity of the host environment could be detected in irradiated AKR recipients as early as age 2 months. The phenotypic changes brought about in leukemia-resistant (AKR x NZB)F1 thymocytes by the leukemia susceptible AKR thymic microenvironment may be the result of a three-component inductive system. PMID- 6244103 TI - Interaction of HMG 14 and 17 with actively transcribed genes. AB - The interaction of HMG 14 and 17 with actively transcribed genes was studied by monitoring the sensitivity of specific genes to DNAase I after reconstitution of HMG-depleted chromatin with HMG 14 and 17. Our experiments lead to the following conclusions: most actively transcribed genes become sensitized to DNAase I by HMG 14 and 17; either HMG 14 or HMG 17 can sensitize most genes to DNAase I; genes transcribed at different rates have about the same affinity for HMG 14 and 17; HMG 14 and 17 bind stoichiometrically to actively transcribed nucleosomes; and HMG 14 and 17 can restore DNAase I sensitivity to purified nucleosome core particles depleted to HMGs. This last observation suggests that during reconstitution, low levels of HMG 14 and 17 can associate with the active nucleosomes in the presence of a 10--20 fold excess of inactive nucleosomes. Consequently, we conclude that besides their association with HMGs, active nucleosomes also have at least one other unique feature that distinguishes them from bulk nucleosomes and insures proper HMG binding during reconstitution. PMID- 6244104 TI - The tRNAAGYSer and tRNACGYArg genes from a gene cluster in yeast mitochondrial DNA. AB - Yeast mitochondrial DNA-pBR322 recombinant DNA molecules screened for rRNA genes were used as a source of DNA for mitochondrial tRNA gene sequence analysis. We report here the sequences of yeast mitochondrial tRNA genes coding for a tRNAAGYSer and a tRNACGYArg. The tRNAAGYSer sequence deduced from the gene is the first reported sequence of a yeast tRNAAGYSer. It is also the second yeast mitochondrial tRNASer gene to be sequenced, and demonstrates unequivocally the presence of mitochondrial encoded serine tRNA isoacceptors. The tRNACGYArg sequence deduced from the gene is the most AT-rich (82%) tRNA sequence ever reported. Whereas all the mitochondrial genes sequenced to date exist singly on the genome and are separated by long stretches of AT-rich DNA, the tRNAACYSer and tRNAcgyarg genes exist in tandem, separated by only 3 bp. This gene arrangement strongly suggests that mitochondrial tRNA genes may be transcribed into multicistronic precursors. PMID- 6244105 TI - Structure and genomic organization of the mouse dihydrofolate reductase gene. AB - The genomic organization of the mouse dihydrofolate reductase gene has been determined by hybridization of specific cDNA sequences to restriction endonuclease-generated fragments of DNA from methotrexate-resistant S-180 cells. The dihydrofolate reductase gene contains a minimum of five intervening sequences (one in the 5' untranslated region and four in the protein-coding region) and spans a minimum of 42 kilobase pairs on the genome. Genomic sequences at the junction of the intervening sequence and mRNA-coding sequence and at the polyadenylation site have been determined. A similar organization is found in independently isolated methotrexate-resistant cell lines, in the parental sensitive cell line and in several inbred mouse strains, indicating that this organization represents that of the natural gene. PMID- 6244106 TI - The actin genes of Drosophila: a dispersed multigene family. AB - We have initiated a study of the organization and expression of the actin genes of D. melanogaster. Using actin gene-specific probes from both chicken and Dictyostelium sources, a clone--denoted lambda DmA2--containing a Drosophila actin gene has been isolated from a representative library of Drosophila genomic DNA cloned in the lambda bacteriophage vector, Charon 4. Southern blotting experiments reveal that there is only one actin structural gene contained in the 17.5 kb Drosophila insert of lambda DmA2 and that the sequences immediately flanking the structural gene are single copy. Observations by electron microscopy of the R loop structures formed by hybridizing total cytoplasmic poly(A)+ RNA from Drosophila embryos to an appropriate subcloned segment of lambda DmA2 indicate that the gene consists of an approximately 70-170 nucleotide leader sequence encoding the 5' portion of the mature mRNA, a 1.65 kb intervening sequence not present in the mRNA and a 1.55 kb sequence containing the major portion of the gene. Using genomic blots with actin-specific probes derived from lambda DmA2, we show that there are six actin genes per haploid Drosophilia genome. They direct the synthesis of three major size classes of mRNA. Using in situ hybridization, the six genes have been localized to six widely dispersed sites on the polytene chromosomes; the locus for lambda DmA2 is 5C on the X chromosome. In vitro translation of mRNA selected hybridization by a DNA segment specific to lambda DmA2 suggests that this particular gene codes for one of the cytoplasmic actin polypeptides. PMID- 6244107 TI - The organization of repetitive sequences in a cluster of rabbit beta-like globin genes. AB - Several complementary procedures were used to identify and characterize DNA sequences which are repeated within a 44 kilobase (kb) segment of rabbit chromosomal DNA containing four different rabbit beta-like globin genes (beta 1 beta 4). Cross-hybridization between cloned DNAs from different regions of the gene cluster indicates the presence of a complex array of repeat sequences interspersed with the globin genes. We classified 20 different repeat sequences into five families whose members cross-hybridize. Electron microscopy was used to determine the location, size and relative orientations of many of the repeat sequences. Both direct and inverted repeats were identified, with sizes ranging from 140 to 1400 base pairs (bp). Each of the four closely linked globin genes is flanked by at least one pair of inverted repeats of 140-400 bp, and the entire set of four genes is flanked by an inverted repeat of 1400 bp. Two of the five repeat families contain repeat sequences of different sizes. We found that the smaller sequence elements can occur individually or in association with the larger repeat sequences, suggesting that the larger repeats may be composed of more than one smaller repeat sequence. The restriction fragments containing the intracluster repeats also contain sequences which are repeated many times in total rabbit genomic DNA, but it is not known whether the genomic and intracluster repeats are the same sequences. The results provide the first demonstration of the relationship between single-copy and repetitive DNA sequences in a large segment of chromosomal DNA containing a well characterized set of developmentally regulated genes. PMID- 6244108 TI - Complete intergenic and flanking gene sequences from the genome of vesicular stomatitis virus. PMID- 6244109 TI - Dependence of the activity of the poliovirus replicase on the host cell protein. AB - Two poliovirus-specific RNA polymerase activities have been identified: a poly(U) polymerase that copies poly(A).oligo(U) and a replicase that copies natural heteropolymers with some preference for poliovirus RNA. Both activities purified together until a step of a salt gradient elution from poly(U)-agarose, when poly(U) polymerase but no replicase was recovered. Addition of a salt wash fraction from the ribisomes of uninfected cells to this poly(U) polymerase fraction reconstituted replicase activity, and a host factor was purified 50 fold from the ribosomal salt wash. None of the available initiation factors or elongation factors for protein synthesis were able to reconstitute replicase activity. Host factor activity could be supplied by adding oligo(U), suggesting that the factor acts at the initiation step of RNA replication. With the purified replicase-host factor combination, only poly(A)-containing RNAs were copied, and a preference for poliovirus RNA was shown. PMID- 6244110 TI - Maternally transmitted resistance to lymphoma development in mice of reciprocal crosses of the RF/J and AKR/J strains. AB - Females but not males of the low-lymphoma RF/J strain transmit a non-Mendelian factor which suppresses the development of lymphoma in F1 crosses with mice of the high-lymphoma AKR/J strain. Suppression of lymphoma was also evident in the first backcross generation to the parental AKR strain, but only when (RF female x AKR male)F1 mice had been the female parent. This "maternal resistance factor" was transmitted independently of the dominant, lymphoma-suppressing Fv-1n allele transmitted by both males and females of the RF strain, but the suppressive capacities of the two factors appeared to be additive. In this cross, F1 progeny of RF females also showed marked suppression of ecotropic murine leukemia virus expression by comparison with mice of the reciprocal F1 cross, but this suppression of virus expression was not detected in the lymphoma-suppressed AKR backcross population. The observation of lymphoma suppression in the absence of ectropic virus suppression in mice of the (RF X AKR)F1 female x AKR male backross generation indicates a qualitative or quantitative difference in the determination of these two effects. PMID- 6244111 TI - Tumor promoters and Kirsten sarcoma virus increase synthesis of a secreted glycoprotein by regulating levels of translatable mRNA. PMID- 6244112 TI - A molecular description of telometic heterochromatin in secale species. PMID- 6244113 TI - Transfer factor and cellular reactivity to varicella-zoster antigen in childhood leukemia. PMID- 6244114 TI - [Manifestations of periodicity in a long term study of children's collectives]. PMID- 6244115 TI - Purine base composition analysis of normal and tumor rat DNA. AB - Chemical and viral induced rat tumors were analyzed for their purine base composition and compared to normal tissue DNA'S. The tumors were induced by 7,12 dimethylbenz[a]anthracene (DMBA), 20-methylcholanthrene (MC), 3,4-benzopyrene (BP), 1,2-dimethylhydrazine (DMH) and Rous sarcoma virus (RSV). Normal DNAs were extracted from colon, caecum, liver, spleen and embryo and used as reference standards for base composition of normal rat DNA. The composition of purines was obtained by spectrophotometric estimation of the total adenine and guanine (A/G) contents after depurination of the DNA with 66% formic acid at 30 degrees C for 18 h and passage over a cationic exchange resin. Statistical comparison of the A/G molar ratios in normal rat DNAs (1.271) to those of chemical-induced primary tumors (1.342) has shown a highly significant increase. No significant differences could be detected when the base composition of the normals were compared to transplanted tumors, whether chemically or virally induced. Possible explanations from a mutational point of view are discussed. PMID- 6244116 TI - [Human spleen: a new and potent source of human interferon for experimental and therapeutic use]. AB - Cells of a single human spleen, cultivated in vitro and induced by Sendai virus, produce constantly more than 10(8) units of interferon per spleen. This interferon can be used for therapeutic assays and new basic investigations. PMID- 6244117 TI - Evidence for lack of innervation of beta-2 adrenoceptors in the blood vessels of the gracilis muscle of the dog. PMID- 6244118 TI - Dual mechanism for inhibition of calcium-dependent action potentials by acetylcholine in avian ventricular muscle. Relationship to cyclic AMP. PMID- 6244119 TI - The mechanism of alpha-adrenergic activation of the dog coronary artery. AB - Norepinephrine (NE) activates isolated coronary conduit arteries by stimulating Ca2+ uptake into the smooth muscle cells. Blockade of Ca2+ influx by removal of Ca2+ from the bathing medium or addition of 10 mM LaCl3 prevents the NE-induced contraction in the dog coronary artery but still allows NE to induce a rapid transient contraction in the rabbit aorta. Under these conditions, NE stimulates 45Ca2+ efflux from rabbit aorta but fails to do so in the coronary artery. The difference in behaviour between the two arteries is attributed by the presence of an intracellular NE-sensitive Ca2+ fraction in the rabbit aorta and its absence from the dog coronary artery. This difference also explains the much greater sensitivity of the NE-induced contractions in the dog coronary to the relaxant effects of the Ca2+ antagonists, D600 and SKF525A, than that seen in the rabbit aorta. High K+-induced contractions of both the coronary artery and the aorta are equally sensitive to the Ca2+ antagonists. PMID- 6244120 TI - Characterization of cell populations isolated from aortas of rhesus monkeys with experimental atherosclerosis. PMID- 6244121 TI - Technetium-99m pyrophosphate uptake in experimental viral perimyocarditis. Sequential study of myocardial uptake and pathologic correlates. AB - The myocardial uptake of technetium-99m pyrophosphate (99mTc-PYP) in perimyocarditis induced by coxsackievirus B3 in BALB/c mice was studied. 99mTc PYP uptake ratio, measured by the ratio of counts/min per gram for the heart to counts/min per gram for the skull, began to increase 5 days after virus inoculation when myocardial necrosis was evident. On the seventh day after the inoculation, 99mTc-PYP ratio reached a maximum. Histologically, fine, dystrophic calcification appeared in the necrotic fibers. 99mTc-PYP uptake was in proportion to the extent of the myocardial lesions. Thereafter, cellular infiltrations increased with time and were most severe on the fourteenth day, but 99mTc-PYP ratio had begun to fade. On the twenty-eighth day, perimyocardial fibrosis increased and calcification was still present, but 99mTc-PYP ratio had decreased. Myocardial uptake with severe pathologic lesions was visualized on a whole-body image on the seventh day after inoculation with the virus. The findings may provide a basis upon which 99mTc-pyp imaging may be applied to viral perimyocarditis in humans. PMID- 6244123 TI - NH2-terminal monoiodination of hexadecapeptide gastrin: a simple procedure for preparation of 125I-gastrin for radioimmunoassays and receptors studies. AB - A simple procedure has been developed for monoiodination of gastrin to a high specific radioactivity. The COOH-terminal hexadecapeptide fragment of gastrin-17 was coupled at the NH2-terminal glycine residue to iodinated 3-(4-hydroxyphenyl) propionic acid N-hydroxysuccinimide ester. The labelled hexadecapeptide was then efficiently separated from unlabelled hexapeptide and other reagents by chromatography on Sephadex G-50 superfine columns. The mean specific radioactivity was 560 microCi/nmol (n = 5). The tracer was stable and useful for three to four months. The present NH2-terminal monoiodination procedure is a valuable supplement to our previous technique for monoiodination of gastrin at tyrosine-12, in that the NH2-terminal labelled gastrin is well bound also to antisera and receptors specific for the tyrosine containing sequence of gastrin. In addition the present procedure requires only simple gel filtration instead of ion-exchange chromatography in order to achieve adequate separation of labelled from unlabelled gastrin. PMID- 6244122 TI - Clinical evaluation of serum levels of tryptophan in hepatobiliary disease. AB - Fasting serum levels of total and free tryptophan, and free fatty acids and albumin, were measured and compared by blood biochemical analysis in patients with hepatobiliary disease and neuropsychiatric symptoms. The serum total tryptophan level tended to be elevated in patients with chronic active hepatitis, hepatic coma and obstructive jaundice, but not significantly. The serum free tryptophan level was significantly elevated in patients with chronic active hepatitis, liver cirrhosis, primary hepatocellular carcinoma and obstructive jaundice. The free tryptophan level was related to the decreased serum albumin level and elevated serum free fatty acid levels, which seems to indicate a connection with liver parenchymal function. The level, however, seemed not to correlate with neuropsychiatric symptoms. PMID- 6244124 TI - A direct, rapid, radioassay for adenosine diphosphatase. AB - Radiolabelled adenosine diphosphate [beta 32Pi]ADP was synthesized from radioactive orthophosphate and adenosine-5'-monophosphate with dicyclohexylcarbodiimide. The purified radioactive adenosine diphosphate was used as the substrate in a rapid, direct, one-step assay for adenosine diphosphatase in human neutrophilic leukocyte homogenates. Certain kinetic properties of the enzyme activity have been determined. PMID- 6244125 TI - The effects of sodium diethyldithiocarbamate, azathioprine, cyclophosphamide, or hydrocortisone acetate administered alone or in association for 4 weeks on the immune responses of BALB/C mice. PMID- 6244126 TI - Impaired monocyte-macrophage cytotoxicity in patients with Hodgkin's disease. PMID- 6244127 TI - Activation of latent Graves' disease in children. Review of possible psychosomatic mechanisms. AB - In some children, psychological events have appeared to be important in the triggering of Graves' disease. This report examines the case histories of three children in whom the appearance of symptomatology of Graves' disease was associated with depression following the death of a loved one. An analysis of neuroendocrine and immunologie pathways suggests that depression, set off by bereavement, causes low levels of norepinephrine in the brain. The latter in turn may mediate an increase in ACTH and cortisol, leading to reductions in immune surveillance and resultant production of thyroid-stimulating immunoglobulins, hence the development of Graves' disease. PMID- 6244128 TI - Acute viral central nervous system infection. PMID- 6244129 TI - Management of pancreatic disorders. PMID- 6244130 TI - The pancreatic cholera syndrome. PMID- 6244131 TI - Insulinoma. PMID- 6244132 TI - The dynamics of calcium phosphate precipitation studied with a new polyacrylamide steady state matrix-model: influence of pyrophosphate collagen and chondroitin sulfate. AB - A novel steady-state gel-matrix model system is described which facilitates the quantitative kinetic study of the influence of media and matrix composition on a precipitation process. The potentialities of the system are illustrated in experiments in which the precipitation of calcium phosphate in a polyacrylamide film is studied as a function of the calcium and phosphate concentration in the solutions flowing along opposite sides of the film. Addition of pyrophosphate to the reactant solutions was found to diminish the (calcium) x (phosphate) millimolar product at which precipitation starts, indicating a positive effect on nucleation. The slope of the curve was found to decrease, which points to a negative influence of pyrophosphate on the crystal growth process. Incorporation of collagen in the matrix did not change the curve, but incorporation of chondroitin sulfate decreased the formation product since the intercept of the curve was reduced. The usefulness of the system compared with test-tube and non steady state gel experiments for calcium phosphate precipitation studies and its significance for the study of in vitro and in vivo precipitation processes in general, are discussed. PMID- 6244133 TI - Oxidative metabolism of alveolar macrophages from young asymptomatic cigarette smokers. Increased superoxide anion release and its potential consequences. PMID- 6244134 TI - Variable glucose metabolism in resting and phagocytizing human alveolar macrophages (HAM) measured by 14CO2 produced from glucose-1-14C. PMID- 6244135 TI - Marijuana, tetrahydrocannabinol, and pulmonary antibacterial defenses. AB - Although marijuana is now consumed extensively, little is known of its biologic effects on the lung. To study this problem, the intrapulmonary inactivation of an aerosolized challenge of Staphylococcus aureus was quantified in rats exposed to graded amounts of fresh marijuana smoke. Controls inactivated 85.1 percent +/- 0.3 percent of the bacteria six hours after inoculation. Following an in vivo accumulative exposure to smoke from progressively increasing numbers of marijuana cigarettes for periods of ten minutes each hour for five consecutive hours, intrapulmonary bacterial inactivation was impaired in a dose-dependent manner. Evaluation of the effects of parenterally administered delta-9 tetrahydrocannabinol (THC) or of exposure to fresh smoke from THC-extracted marijuana placebo cigarettes indicated that the cytotoxin in marijuana was not related to the primary psychomimetic component. Thus, marijuana smoke is toxic to the lung and impairs the pulmonary antibacterial defense system in a dose dependent manner. PMID- 6244136 TI - Family-centered group care. AB - Alternate frameworks for a model of residential group care focused on the family have the primary objective of early discharge from group care. The proposals are based on an agency's experience. PMID- 6244137 TI - Insulinoma: diagnostic and therapeutic experiences in 60 cases. PMID- 6244138 TI - Toxic polyneuropathy due to chronic allyl chloride intoxication: a clinical and experimental study. PMID- 6244139 TI - Experimental prevention of venous thrombosis. AB - Modern antithrombotics are no more represented merely by anticoagulants. The experiments with a series of thrombosis models enabled us to redefine several new groups appearing as yet under the name "antiplatelet agents" or "antiaggregants". The group comprises particularly acetylsalicylic acid, dipyridamole, hydroxychloroquine, sulfinpyrazone, clofibrate and suloctidyl. It was demonstrated experimentally that these drugs act predominantly by increasing endothelial stability against various noxious agents. This stabilizing effect, independent on the anticoagulant activity, is present also after the administration of oral anticoagulants in doses by one order lower in comparison with the anticoagulant dosage. In fact, the latter dosage has an opposite effect on endothelium and increases the number of circulating endothelial cells. Nevertheless, this unfavourable effect may be inhibited by suitable endotheloprotective drugs (e. g. prenylamine) and in this way an important portion of bleeding complications after oral anticoagulants may be abolished. PMID- 6244140 TI - Effects of plasma estrogen sulfates in mammary cancer cells. PMID- 6244141 TI - Binding of endogenous iodothyronines to isolated liver cell nuclei. AB - The metabolic role of a number of the metabolites of T4 is unknown. Hence, these iodothyronines, now known to be present in human serum, were tested for their ability to displace [125I]T3 from specific binding sites in isolated pig liver nuclei. Compared with T3 (1.0), the molar inhibition ratios of the analogs tested were: triiodothyroacetic acid, 4.4; T4 6.2; 3.3'-diiodothyronine, 56; 3,5 diiodothyronine, 245; rT3, 264; and 3',5'-diiodothyronine, 60,000. In isolated pig liver nuclei, the Ka for T3 was 1.73 +/- 0.21 X 10(9) M-1 and that for T4 was 0.17 +/- 0.06 X 10(9) M-1. Nuclei stored in liquid nitrogen for up to 8 weeks leaked bound [125I]T3 into the supernatant during the incubation period. No loss of bound [125I]T3 was observed with freshly prepared nuclei. The data indicate that, with the exception of T3 and T4, iodothyronines derived from T4 are unlikely to modulate the interaction of T3 with its receptor unless their perireceptor concentration is significantly greater than their serum concentration. PMID- 6244142 TI - Receptor-binding affinity of gonadotropin-releasing hormone analogs: analysis by radioligand-receptor assay. PMID- 6244143 TI - Studies on the receptor for luteinizing hormone in a purified plasma membrane preparation from rat ovary. PMID- 6244144 TI - In vitro stimulation by estrogen of guanosine 3',5'-monophosphate accumulation in incubated rat uterus. PMID- 6244145 TI - Target tissues for relaxin in the rat: tissue distribution of injected 125I labeled relaxin and tissue changes in adenosine 3',5'-monophosphate levels after in vitro relaxin incubation. PMID- 6244146 TI - The interaction of relaxin with the rat uterus. I. Effect on cyclic nucleotide levels and spontaneous contractile activity. AB - Three different preparations of relaxin elevated cAMP levels in isometrically suspended uterine strips obtained from estrogen-primed female rats in the presence of phosphodiesterase inhibitors. The effect was time and dose dependent, with maximal response at 20 min and 1 microgram/ml, respectively. No changes in cGMP levels were observed. No significant response was observed in ileum, vas deferens, epididymis, or testicular capsule. In the absence of phosphodiesterase inhibitors, relaxin markedly suppressed spontaneous contractile activity at doses of 0.36 and 0.96 microgram/ml but did not elevate cAMP in this dose range. While the beta-adrenergic antagonist propranolol suppressed both the relaxant action and cAMP stimulation promoted by isoproterenol, it did not interfere with the effect of relaxin on these same parameters. Relaxin is therefore capable of relaxing uterine muscle and elevating cAMP by mechanisms which probably do not require beta-adrenergic mediation. It is not clear at present whether the effects of relaxin on cAMP levels and contractile activity are causally related. PMID- 6244147 TI - Effects of androgen on induction of gonadotropin receptors and gonadotropin stimulated adenosine 3',5'-monophosphate production in rat ovarian granulosa cells. PMID- 6244148 TI - The effect of somatostatin on the activation of adenosine 3',5'-monophosphate dependent protein kinase in isolated rat islets of Langerhans. AB - Somatostatin has been reported to inhibit the increases in cAMP levels induced by glucagon in isolated islets of Langerhans. The present study was undertaken to test whether the reported effects of somatostatin on islet cAMP levels were also reflected in changes in the cAMP-dependent protein kinase activity. Isolated islets were found to contain both isoenzymes of the cAMP-dependent protein kinase. In the presence of theophylline (2 mM), glucagon (2.9 X 10(-6) M) increased the islet protein kinase activity ratio from 0.24 +/- 0.02 to 0.55 +/- 0.02. Somatostatin (6.6 X 10(-7) M) fully inhibited both the glucagon (2.9 X 10( 7) M)- and theophylline (2 mM)-induced increases in the protein kinase activity ratio. Omission of Ca2+ from the islet incubation media did not alter the inhibitory effect of somatostatin on the glucagon-dependent activation of the cAMP-dependent protein kinase. The present study has demonstrated that in the islets of Langerhans, glucagon-dependent activation of the cAMP-dependent protein kinase can be modulated by somatostatin. PMID- 6244149 TI - Vasoactive intestinal peptide- and adrenocorticotropin-stimulated adenyl cyclase in cultured adrenal tumor cells: evidence for a specific vasoactive intestinal peptide receptor. AB - Vasoactive intestinal peptide (VIP) has been shown to be steroidogenic in monolayer cultures of a murine adrenal tumor but must be present at concentrations about 100-fold greater than ACTH to elicit the same degree of stimulation. Both peptides enhanced cAMP synthesis, although there was again a difference of 2 orders of magnitude in the dose-response curves. In contrast, VIP stimulated adenyl cyclase activity of tumor membranes in the same concentration range as ACTH. Maximum activity with VIP was less than that with ACTH in the absence or presence of a saturating amount of guanylyl imido-diphosphate. Saturating amounts of both peptides stimulated activity to levels greater than that with either ACTH or VIP alone, but the activity was not fully additive. An o nitrophenyl sulfenyl derivative of ACTH inhibited ACTH-stimulated adenyl cyclase activity but not VIP-stimulated activity. Low concentrations of calcium potentiated the ability of submaximal doses of ACTH to stimulate adenyl cyclase but had no effect on the response to VIP. Concentrations of secretin or glucagon comparable to that of VIP did not stimulate steroidogenesis in intact cells. These data suggest that VIP may bind to a unique receptor which may be distinct from that of ACTH. PMID- 6244150 TI - Fetal-maternal adrenocorticotropin and corticosterone relationships in the rat: effects of maternal adrenalectomy. PMID- 6244151 TI - Pituitary cyclic nucleotides and thyrotropin-releasing hormone action: the relationship of adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate to the release of thyrotropin and prolactin. PMID- 6244152 TI - Primer specificity of ribosome-associated poly(A) polymerase from Ehrlich ascites tumour cells. AB - The reaction product of the ribosomal poly(A) polymerase [ATP(UTP):RNA nucleotidyltransferase] is analyzed. Two systems are used in vitro: (a) isolated polyribosomes with endogenous enzyme and RNA primer and (b) purified enzyme with total polyribosomal RNA as primer. In the polyribosome system about 50% of the [3H]AMP label is in poly(A)-containing mRNA. This RNA displays a heterogeneous size ditribution in the range of 8--30 S with a maximum at about 14 S. Upon denaturation the maximum is shifted towards the 10-S zone. The poly(A) polymerase catalyzes the addition of 12--18 adenylate residues to pre-existing mRNA poly(A) sequences of 40--160 residues. The [3H]AMP incorporated into poly(A)-lacking RNA is mainly in a fraction with an electrophoretic mobility corresponding to 4-S RNA. In the purified enzyme system, specificity towards poly(A)-containing mRNA is lost to a considerable extent. Only 10% of the [3H]AMP label is retained by oligo(dT)-cellulose. The bulk of the product is in 18-S rRNA and heterogeneous small molecular weight RNA. We conclude that the ribosome-associated poly(A) polymerase is most likely the enzyme responsible for the cytoplasmic polyadenylation of poly(A)-containing mRNA in vivo. PMID- 6244153 TI - Inhibitory effects of 'cap' analogues on globin mRNA and encephalomyocarditis RNA translation in a reticulocyte cell-free system. AB - The cap analogues 7-methylguanosine 5'-phosphate [m7G(5')p], 7-methylguanosine 5' triphosphate [m7G(5')ppp] and 2'-O-methylguanosine 5'-triphosphate [Gm(5')ppp] inhibit the translation of capped globin mRNA and encephalomyocarditis (EMC) RNA (a naturally uncapped mRNA) in a reticulocyte cell-free system. This inhibition occurs at the level of protein synthesis initiation and is of a competitive type since it can be overcome by increasing the mRNA concentration. However, the translation of globin mRNA is more sensitive to the inhibitory effects of the cap analogues m7G(5')p and m7G(5')ppp than translation of EMC RNA. The same spectra of specific inhibition is also observed with some other initiation inhibitors such as aurintricarboxylic acid, which inhibits mRNA binding, but not with pactamycin which does not affect mRNA interaction. A model is presented suggesting that this preferential inhibition by cap analogues could be explained mainly by the different affinities of globin mRNA and EMC RNA for the initiation complexes between 40-S subunits and Met-tRNAf. Moreover Gm(5')ppp cannot be considered simply as a cap analogue since it also affects some step prior to mRNA binding. PMID- 6244154 TI - Phosphate binding to liver alcohol dehydrogenase studied by the rate of alkylation with affinity labels. AB - In this work we report that phosphate anions interact with the anion binding site of alcohol dehydrogenase from horse liver. In protection experiments against the two affinity labels, iodoacetic acid and bromo-imidazolylpropionic acid, the dissociation constant for the enzyme-phosphate complex at pH 7.0 is, based on total phosphate, found to be 20 +/- 5 mM. The 1,4-piperazinediethanesulfonate anion has a lower affinity for the anion binding site, the dissociation at pH 7.0 being 130 +/- 20 mM. The anion-independent dissociation constants for the reversible enzyme-affinity label complexes are at pH 7.0, 1.35 +/- 0.2 mM for iodoacetic acid and 0.39 +/- 0.05 mM for bromo-imidazolylpropionic acid. These findings have important implications with respect to past and future work on this well known enzyme. PMID- 6244155 TI - Electron paramagnetic resonance of the copper in dopamine beta-monooxygenase. Rapid reduction by ascorbate, the steady-state redox level, chelation with EDTA, and reactivation of the apoenzyme by added copper. AB - The water-soluble form of dopamine beta-monooxygenase from bovine adrenal medulla was studied. Addition of excess CuSO4 to purified enzyme preparations followed by extensive ultrafiltration against copper-free buffer at pH 7.0, gave preparations with about four copper atoms per enzyme tetramer of Mr 290 000. The enzyme-bound copper was shown by the rapid-freeze technique and electron paramagnetic resonance (EPR) to be reduced by ascorbate at a rate which was faster than the overall catalytic rate; about 10% of the copper was oxidized to Cu(II) during steady-state catalysis in the presence of excess ascorbate. These results support an electron-transfer function of the enzyme-bound copper during catalysis and indicate that the reduction by ascorbate is not the rate-limiting step. The enzyme-bound copper was rapidly chelated by EDTA at pH 7.0., and the apoenzyme thus obtained after dialysis revealed no EPR-detectable copper. Addition of CuSO4 to the apoenzyme gave an EPR spectrum similar to that of the native enzyme, and the apoenzyme was fully reactivated by the optimal concentration of CuSO4 in less than 2 s. PMID- 6244156 TI - Two distinct poly(A) polymerases isolated from the cytoplasm of Ehrlich ascites tumour cells. AB - The poly(A) polymerases from the cytosol and ribosomal fractions of Ehrlich ascites tumour cells are isolated and partially purified by DEAE-cellulose and phosphocellulose column chromatography. Two distinct enzymes are identified: (a) a cytosol Mn2+-dependent poly(A) polymerase (ATP:RNA adenylyltransferase) and (b) a ribosome-associated enzyme defined tentatively as ATP(UTP): RNA nucleotidyltransferase. The cytosol poly(A) polymerase is strictly Mn2+-dependent (optimum at 1 mM Mn2+) and uses only ATP as substrate, poly(A) is a better primer than ribosomal RNA. The purified enzyme is free of poly(A) hydrolase activity, but degradation of [3H]poly(A) takes place in the presence of inorganic pyrophosphate. Most likely this enzyme is of nuclear origin. The ribosomal enzyme is associated with the ribosomes but it is found also in free state in the cytosol. The purified enzyme uses both ATP and UTP as substrates. The substrate specificity varies depending on ionic conditions: the optimal enzyme activity with ATP as substrate is at 1 mM Mn2+, while that with UTP as substrate is at 10- 20 mM Mg2+. The enzymes uses both ribosomal RNA and poly(A) [but not poly(U)] as primers. The purified enzyme is free of poly(A) hydrolase activity. PMID- 6244157 TI - Mitochondrial ATP:AMP phosphotransferase from beef heart: purification and properties. AB - ATP:AMP phosphotransferase has been purified 186-fold from beef heart mitochondria in an overall yield of 30%. The purified enzyme, Mr 31 500, has a specific activity of 800 U/mg and was found to be a homogeneous protein by constancy of specific activity across the elution peak following passage through an Affi-Gel Blue agarose column and by dodecylsulfate gel electrophoresis. Isoelectrofocusing shows a minor peak of activity that arises again when the major peak is re-focused. The pI of the enzyme is 9.30 and the optimum pH of activity is 5.8 in the forward reaction (formation of ADP) and 8.0 in the reverse reaction. The enzyme requires the presence of a divalent metal ion, namely Mg2+, Co2+, Ca2+ Mn2+, Ni2+ and Zn2+ in decreasing order of activity and is influenced by NaCl. It shows rigorous specificity for AMP (dAMP) was phosphate acceptor but is rather unspecific for the triphosphate donor since, UTP, CTP, ITP and GTP may substitute for ATP (dATP). ATP and MgATP (dATP was not tested) bind to the enzyme with dissociation constants of 0.122 and 0.132 mM respectively, while AMP (dAMP was not tested), UTP, CTP, ITP and GTP binding could not be detected by the dialysis equilibrium technique used. Amino acid analysis gave the following composition as residues: 26 aspartic acid or asparagine, 14 threonine, 17 serine, 27 glutamic acid or glutamine, 24 proline, 19 glycine, 25 alanine, 17 valine, 8 methionine, 14 isoleucine, 31 leucine, 5 tyrosine, 9 phenylalanine, 6 histidine, 25 lysine, 15 arginine, 4 half cystine (no free sulfhydryls) and no tryptophan, giving a total of 286 residues. The purified mitochondrial adenylate kinase is not a contaminating heart cytosolic enzyme. ATP:AMP phosphotransferase was extracted from beef heart cytosol depleted of mitochondria and brought to homogeneity. Determinations of pI, Mr and amino acid composition showed that the heart mitochondrial and cytosolic adenylate kinases are different isozymes. PMID- 6244159 TI - Nuclear-magnetic-resonance studies of eukaryotic cytochrome c. Assignment of resonances of aliphatic amino acids. AB - The aliphatic regions of the nuclear magnetic resonance spectra of horse ferricytochrome c and horse ferrocytochrome c are described. Resonance assignments have been made using NMR double-resonance techniques, spectral comparison of related proteins, the perturbing effects of extrinsic probes, and from knowledge of the X-ray structure of cytochrome c. There are eight firmly assigned methyl resonances of ferrocytochrome c and seven firmly assigned methyl resonances of ferricytochrome c. PMID- 6244158 TI - Nuclear-magnetic-resonance studies of eukaryotic cytochrome c. Assignment of resonances of aromatic amino acids. AB - The aromatic regions of the nuclear magnetic resonance spectra of horse ferricytochrome c and horse ferrocytochrome c are described. Resonance assignments have been made using NMR double-resonance techniques, spectral comparison of related proteins, the perturbing effects of extrinsic probes, and from knowledge of the X-ray structure of cytochrome c. 33 resonances arising from 39 aroumatic protons of ferrocytochrome c, and 18 resonances arising from 27 aromatic protons of ferricytochrome c have been assigned. PMID- 6244160 TI - Nuclear-magnetic-resonance studies of ferrocytochrome c. pH and temperature dependence. AB - The pH dependence and the temperature dependence of the nuclear magnetic resonance spectrum of horse ferrocytochrome c are described. This protein is very stable; it maintains an ordered structure over the pH range 4 to 12 at 25 degrees C and over the temperature range 4 degrees C to 97 degrees C at pH 7.0. The dynamic characteristics of the conformation of ferrocytochrome c were investigated. Particular emphasis was laid on the aromatic resonances and resonances of methyl groups shifted far upfield. Tyr-48 and Phe-46 were found to be relatively immobile whilst a region of the protein close to Ile-57 was found to be relatively flexible. PMID- 6244161 TI - The stability of ferricytochrome c. Temperature dependence of its NMR spectrum. AB - The temperature dependence of the nuclear magnetic resonance spectrum of horse ferricytochrome c is described. The protein maintains an ordered structure over the temperature range 20 degrees C to 77 degrees C. The temperature dependence of the spectrum of ferricytochrome c arises from a number of causes including the paramagnetism of the ferric ion and protein structural changes. Preliminary analysis of the data show that the region of the protein about Ile-57 is flexible. Comparison of the data with the analogous data for horse ferrocytochrome c reveals that there is a small difference in structure between cytochrome c in its two oxidation states in the region about Ile-57. PMID- 6244162 TI - The solution structures of tuna and horse cytochromes c. AB - The nuclear magnetic resonance spectra of tuna ferricytochrome c and tuna ferrocytochrome c are described. Resonance assignments are made using NMR double resonance techniques. A comparison of the NMR data for tuna cytochrome c with the previously reported data for horse cytochrome c shows that the proteins have virtually identical main-chain folds. Three regions of local conformational differences have been distinguished. PMID- 6244163 TI - Interactions of elongation factor 2 (EF-2) with guanine nucleotides and ribosomes. Binding of periodate-oxidized guanine nucleotides to EF-2. AB - Interactions of rat liver elongation factor 2 (EF-2) with guanine nucleotides and ribosomes were studied by equilibrium dialysis and sedimentation methods. GDP (Kd = 0.5 microM) or GDP-Mg2+ (Kd = 1.57 microM) displayed a higher affinity in the formation of a binary complex with EF-2 than GTP (Kd = 2.68 microM), GTP-Mg2+ (Kd = 2.77 microM), or guanosine 5'-[beta, gamma-methylene]triphosphate (GuoPP[CH2]P) (Kd = 24.0 microM). NaIO4-oxidized guanine nucleotides (oGDP) (Kd = 38 microM) and oxidized/reduced guanine nucleotides (orGDP) (Kd = 27 microM) had lower affinites to the binding site on EF-2 than those of GDP or GTP. However, the binding of oGDP, oGTP or oGuoPP[CH2]P to EF-2 resulted in the formation of a stable product which could be recovered by the nitrocellulose filter technique or by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. In the presence of ribosomes and EF-2 the formation of a new binding site (or a different conformation of the binding site) with a higher affinity for GuoPP[CH2]P-Mg2+ (Kd = 0.26 microM) than fof GDP-Mg2+ (kd = 9.3 microM) became apparent. The presence of ribosomes thus appeared to favor the formation of a complex involving guanosine triphosphates. Adenosine diphosphate ribosylated EF-2 (ADP-Rib-EF-2) in its turn could bind to the ribosome with high affinity even without guanosine nucleotides (Kd = 0.18 microM). GuoPP[CH2]P increased to some extent the affinity of ADP-Rib-EF-2 for its ribosomal binding site (Kd = 0.05 microM). PMID- 6244164 TI - Rapid separation of rat peritoneal mast cells with Percoll. AB - Rat peritoneal mast cells were separated by using density gradients of PVP-coated silica particles (Percoll). Mast cells were either isolated on preformed Percoll gradients or cell separation was made simultaneously with the gradient formation. Both procedures resulted in mast cell suspensions of 95 to 99 per cent purity. As tested by Ruthenium red staining and electron microscopy, the isolated mast cells showed a very good preservation of cell structure and reacted easily to the degranulating agent Compound 48/80. Practically all mast cells could be recovered from the peritoneal cell suspension. Percoll was found to be superior to earlier isolation procedures by giving a practically pure and intact mast cell suspension and by avoiding cell aggregation. PMID- 6244166 TI - Regulation of the contractile system of blood platelets. PMID- 6244165 TI - Study of a virus-induced myeloproliferative syndrome associated with tumor formation in mice. PMID- 6244167 TI - Induction of cAMP receptors by disaggregation of the multicellular complexes of Dictyostelium discoideum. PMID- 6244169 TI - A plasma membrane-associated phospholipase in SV40-transformed 3T3 cells. PMID- 6244168 TI - Effect of 2-deoxyglucose on lysosomal enzymes in cultured human skin fibroblasts. PMID- 6244170 TI - Relations between the effect of tetanus toxin on the neuromuscular transmission and histological functional properties of various muscles of the rat. PMID- 6244171 TI - Cholinergic neurotransmission in retinal spreading depression. AB - Experiments performed to demonstrate the participation of cholinergic synapses in retinal spreading depression (SD) have shown that: (1) acetylcholine (ACh) is liberated during SD, its concentration increasing up to 10(-4) mM in the superfusate of one eye cup; (2) the susceptibility of the retina to SD and the velocity of propagation of circling SD are influenced by cholinergic and anticholinergic drugs. ACh 1 mM is effective in eliciting the reaction, whereas d tubocurarine 0.01 mM and atropine 0.25 mM block this effect. Prostigmine 0.075 mM is able to trigger the reaction and also potentiates the effect of ACh. The velocity of propagation is decreased by ACh 0.25-1.0 mM and prostigmine 0.030 mM, which also potentiate this effect of ACh. Pulses of d-tubocurarine 0.005-0.030 mM and atropine 0.025-0.30 mM decrease the velocity of propagation. However, they block the effect of ACh if they are continuously present in the superfusing solution; (3) the effects of ACh are not blocked by tetrodotoxin 3.19 x 10(-3) mM. PMID- 6244172 TI - Autoradiographic localization of 3H-GABA and 3H-muscimol binding in rat cerebellar cultures. AB - Autoradiographic studies were conducted on the binding of 3H-GABA and 3H-muscimol in cultures of rat cerebellum. Binding sites for both substances were observed on many cerebellar neurones, such as Purkinje cells and interneurones, but not on glial cells. Binding of 3H-GABA and 3H-muscimol was inhibited by unlabelled GABA and by the GABA antagonist bicuculline. PMID- 6244173 TI - Increase in pituitary melanocyte-stimulating hormone activity of genetically obese (ob/ob) mice. AB - Melanocyte-stimulating hormone (MSH) activity was measured in the pituitaries of genetically obese and lean control mice using the frog skin bioassay. Obese mice pituitaries demonstrated very significantly elevated levels of biologically active MSH when compared to their lean littermates. These results support the hypothesis that the elevated levels of pituitary hormones found in obese mice possesses true biological activity. PMID- 6244174 TI - Genesis of concentric laminated inclusions in the nucleus. AB - Single-membrane-bound inclusions containing zymogen granules were found in pancreatic acinar cells. Images were seen suggesting that the concentric laminated inclusion is derived by hydration and fusion of such granules within the inclusion. PMID- 6244175 TI - Opposite effects of beta-adrenoceptor stimulation and 8-bromo-cyclic AMP on potassium efflux in mammalian heart muscle. AB - beta-adrenoceptor stimulation by isoprenaline increases the potassium efflux in beating guinea-pig atria. This effect is not mimicked by 8-bromo-cyclic AMP, a cyclic AMP analogue which exerts a positive inotropic effect in this preparation. PMID- 6244176 TI - Adenylate cyclase in the developing rat cerebral cortex and olfactory bulb. AB - Activities of adenylate cyclase, measured either in the absence or presence of sodium fluoride and Triton X-100, are determined in cerebral cortex and olfactory bulb homogenate of rats of 1 to 35 days of postnatal age. Differences in properties of the enzyme in the 2 structures are demonstrated. PMID- 6244177 TI - A model for the cytochrome b dimer of the ubiquinol: cytochrome c oxidoreductase as a proton translocator. PMID- 6244178 TI - The identification of a transformed cell growth factor in lactalbumin hydrolyzate as biotin. PMID- 6244179 TI - ATP-Mg-dependent phosphorylase phosphatase in mammalian tissues. PMID- 6244180 TI - Cell metabolism affects the density of beta-adrenergic receptors in intact rat reticulocytes. PMID- 6244181 TI - A highly purified rat-liver phosphoprotein phosphatase preparation with activity towards phosphopyruvate kinase (type L). PMID- 6244182 TI - The iron-sulphur centres of aerobically-grown Escherichia coli K12. PMID- 6244183 TI - An EPR study of cytochromes from spinach chloroplasts. PMID- 6244184 TI - Time-dependent stabilisation of the TSH-TSH receptor complex. PMID- 6244185 TI - Kinetic studies on the H2O2(O2-)-forming enzyme in guinea pig leukocytes. PMID- 6244186 TI - The effect of vinblastine on the glucagon, basal and GTP-stimulated states of the adenylate cyclase from rat liver plasma membranes. PMID- 6244187 TI - Role of multisite phosphorylation in the regulation of ox kidney pyruvate dehydrogenase complex. PMID- 6244188 TI - Relationship between S1 endonuclease-sensitivity and number of superhelical turns in a negatively-twisted DNA. PMID- 6244189 TI - Random protection of single cut restriction endonuclease sites in SV40 mini chromosomes assembled in vitro. PMID- 6244190 TI - Can partial methylation explain the complex fragment patterns observed when plant mitochondrial DNA is cleaved with restriction endonucleases? PMID- 6244191 TI - Partial characterization of the genome of the 'endosymbiotic' cyanelles from Cyanophora paradoxa. PMID- 6244192 TI - Stability of the nitrosyl-sirohaem complex of plant nitrite reductase, investigated by EPR spectroscopy. PMID- 6244193 TI - Mapping of the interaction domain for purified cytochrome c1 on cytochrome c. PMID- 6244194 TI - ATPase and adenylate cyclase distribution in skeletal muscle membranes. PMID- 6244195 TI - A new sequence-specific endonuclease from a thermophilic cyanobacterium, Mastigocladus laminosus. PMID- 6244196 TI - [Changing concepts of hormones]. PMID- 6244197 TI - [Properties of opioid receptor binding in the rat brain (author's transl)]. PMID- 6244198 TI - Study of the effects of hydrocortisone and hydrocortisone 17-butyrate ointments on plasma ACTH levels and Synacthen responses in children with eczema. AB - This study compares the effects on the hypothalamo-pituitary adrenal (HPA) axis of two dosage schedules of hydrocortisone 17-butyrate and hydrocortisone ointments in 20 children suffering from eczema. Children with moderately extensive eczema received either 30 g of 0.1% hydrocortisone 17-butyrate or 30 g of 1% hydrocortisone ointment weekly for 4 weeks without occlusion. Children with extensive eczema received either 60 g of hydrocortisone 17-butyrate or 60 g of hydrocortisone weekly for 4 weeks. All four groups showed some clinical improvement. Although many of the children appeared to have some impairment of adrenal function prior to entering the trial, no further significant depression of the HPA axis as reflected by the plasma ACTH levels and a 30-min Synacthen test was observed during the trial. On the basis of 4 weeks' treatment, hydrocortisone 17-butyrate did not have a significantly different effect on the HPA axis in children from that of hydrocortisone. PMID- 6244199 TI - Attempts to transform primate cells in vitro by herpes simplex virus. AB - Attempts were made to transform human cervical cells and nonhuman primate cells with herpes simplex virus (HSV). None of 129 cervical cell cultures obtained from 29 patients and infected in vitro with various strains of HSV became transformed. Established cell lines of marmoset cells infected with HSV showed no characteristics of malignant transformation. Parallel cultures of rat embryo cells maintained under similar experimental conditions became malignant. PMID- 6244200 TI - Search for mammalian type-C retrovirus polypeptides on infected animal cells and human tumor cell lines using interspecies-reacting antibodies. AB - Cells producing endogenous and exogenous type-C retroviruses of murine, feline and primate origin were evaluated for expression of those virus-specific cell surface antigens which cross-react with antibodies to interspecies determinants of mammalian type-C viral polypeptides. Surface polypeptides of cells replicating endogenous and exogenous type-C retroviruses were iodinated by the lactoperoxidase method. Labelled antigens were immunoprecipitated and analyzed in polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. This method detected gp71 and less frequently p15E/p12E on the surface of virus producing cells; in addition, p27 was found on F422 cells replicating feline leukemia virus. Antibodies to the membrane protein p15E displayed the broadest cross-reactivity but only antibodies to gp71 mediated complement-dependent interspecies cell lysis. The pattern of cross-reactivity reflected known genetic relationships among these mammalian viruses. Although antiserum to the simian sarcoma virus complex (SSV) was strongly cytotoxic to some human tumor cell lines, this reactivity could not be attributed to antibodies cross-reacting with SSV gp71. PMID- 6244201 TI - Subcellular localization of some glycolytic enzymes in parasitic flagellated protozoa. AB - 1. The glycolytic enzymes of Tritrichomonas foetus, unlike those of Trypanosoma brucei, are apparently not located in microbody-like organelles (glycosomes) but appear to occur in the cytosol. 2. The localization of the glycolytic enzymes in Crithidia fasciculata and in the epimastigote and trypomastigote forms of Trypanosoma cruzi is however similar to that in T. brucei. 3. No evidence was obtained for the existence of glycolytic enzyme-containing microbodies in rat liver. 4. The glycosome is probably an organelle unique to members of the Kinetoplastida. PMID- 6244202 TI - Spectrophotometric determination of H2O2-generating oxidases using oxyhemoglobin as oxygen donor and indicator. AB - 1. Spectrophotometric determination of oxygen uptake using oxyhemoglobin as oxygen donor and indicator was used for assay of H2O2-generating oxidases like monoamine oxidase and glucose oxidase. 2. In order to decompose H2O2 formed during the oxygen uptake, catalase and methanol (or ethanol) was added to the respiratory system. At pH values higher than 7.5 the oxydation of deoxygenated hemoglobin to methemoglobin was less than 3%. 2. Oxidases with low Km for oxygen can be assayed using the spectrophotometric method if suitable correction factors are introduced into the calculation of oxygen uptake. The correction factor represents the ratio of the rate of formation (or disappearance) of one of the reactants and the rate of oxyhemoglobin deoxygenation, measured under identical experimental conditions. PMID- 6244203 TI - Characterization and comparison of two plasma membrane reference enzymes with those of other organelles during mammalian embryogenesis. AB - 1. Optimal assay conditions for two plasma membrane reference enzymes, alkaline phosphodiesterase 1 and 5'-nucleotidase, were determined in homogenates of rat embryos obtained on the 14th day of gestation and were found to be different than those reported for adult tissues. 2. Measurements of various organelle reference enzyme activities on the 14th and 15th days of gestation revealed a pattern of selective rates of subcellular organelle biogenesis during this period: lysosomes greater than mitochondria greater than endoplasmic reticulum = plasma membranes. PMID- 6244204 TI - Effects of lysomotropic agents, and of microfilament- and microtubule-disrupting drugs on the activation of casein-gene expression by prolactin in the mammary gland. AB - The organ-culture technique was used to investigate the effects of lysomotropic agents (NH4Cl and chloroquine) and of modifiers of microfilaments (cytochalasin B) and microtubules (colchicine) on the induction of casein synthesis and the accumulation of casein mRNA by prolactin in the rabbit mammary gland. Neither chloroquine nor NH4Cl altered the lactogenic action of prolactin. Cytochalasin B attenuated the response to prolactin in terms of casein synthesis. However, this drug did not hamper the accumulation of casein mRNA. Colchicine exhibited a marked specific inhibitory effect on the induction of casein synthesis. It also prevented the accumulation of casein mRNA. These results suggest that a putative degradation of the internalized prolactin--receptor complex by lysosomes is not strictly involved in prolactin action. In addition, the integrity of the microfilaments seems unnecessary in the process of casein-gene activation by prolactin. By contrast, the integrity of the microtubule network seems absolutely necessary to ensure the transmission of prolactin information to the nucleus. PMID- 6244205 TI - The uptake and release of ponasterone A by the Kc cell line of Drosophila melanogaster. AB - The association of ponasterone A (PNA) and 20-hydroxyecdysone with Kc cells is commensurate with their biological activity on this Kc cell line, the physiological activity ratio for PNA, 20-hydroxyecdysone and ecdysone is 1 : 50 : 2000, resp. Both association and release of [3H]-PNA are temperature-dependent, the activation energy was calculated as 16.7 cal (Arrhenius analysis). This association is compatible with unlabelled PNA and various ecdysteroids. The KD for PNA (Scatchard analysis) was estimated as 3.6 x 10(-9) M, giving the number of binding sites as approx. 1800 per cell. PMID- 6244206 TI - Competition of various LH--RH analogs and fragments with 135I-LH--RH for specific binding sites on isolated pituitary plasma membranes. AB - The displacement by various LH--RH analogs and fragments of 125I-LH--RH specifically bound to plasma membranes isolated from rat anterior pituitaries was investigated. The addition of increasing amounts of unlabelled LH--RH resulted in an increasing displacement of bound 125I-LH--RH. When some fragments of LH--RH or of an analog with little biological activities were incubated, a much weaker affinity for LH--RH binding sites could be observed. No correlation between biological effectiveness and binding affinity was, however, found when several highly active LH--RH analogs were tested. The potent analogs competed much less efficiently for specific binding sites on isolated plasma membranes than LH--RH. Binding experiments with iodine-labelled (D-Ser(But)6-LH--RH(1--9)-nonapeptide ethylamide indicated that the small binding affinity of the superactive analog may be due to a lower association rate while the dissociation rate is comparable to that of LH--RH. Contrary to LH--RH, no binding equilibrium was reached during 2 h of incubation of the analog with plasma membranes. The physiological role of LH--RH binding sites on isolated pituitary plasma membranes remains to be elucidated. PMID- 6244207 TI - Metabolic activity of diabetic monocytes. PMID- 6244208 TI - The activity of N-acetylglucosamine kinase in rat gastric mucosa. AB - The activity of N-acetylglucosamine kinase in the rat glandular stomach was studied to elucidate its participation in aspirin-induced ulcers, and the effect of proglumide, an anti-ulcer agent which was found to increase gastric mucosal hexosamine, on this enzymatic activity was also studied. N-Acetylglucosamine kinase activity was found to be significantly higher in the antrum than in the corpus, the antrum being 1.3--1.9 times as active as the corpus. The mucosal layer itself was about 1.8--2.0 times as active as the whole tissue of the glandular stomach. This enzymatic activity in the glandular stomach was found to decrease slightly after fasting and to further decrease after intragastric administration of aspirin (100 mg/kg). The pylorus-ligated rats showed a significant decline of this enzymatic activity following the administration of aspirin. Acceleration of N-acetylglucosamine kinase activity with proglumide was demonstrated in vivo and in vitro experiments. Prior treatment with proglumide prevented aspirin-induced ulcers and correspondingly stimulated this enzymatic activity. These results suggest that the activity of N-acetylglucosamine kinase in the rat glandular stomach closely parallels the distribution and localization of gastric hexosamine, glycosaminoglycans, and glycoproteins. A decrease of this enzymatic activity correlates with the production of ulcers by aspirin. The mechanism by which proglumide increases gastric hexosamine is at least partly attributed to the activation of N-acetylglucosamine kinase in the glandular stomach. PMID- 6244209 TI - Isolation of transposon TnA from plasmid RP4 carrying two copies of this element. AB - Employing heteroduplex and restriction analyses, two inverted copies of a 3.2.10(6) dalton transposable sequence, TnA, were found in RP4::TnA, a spontaneously arisen derivative of the plasmid RP4. Integration of the second copy of TnA causes loss of the conjugative properties of RP4. Both TnA sequences in RP4::TnA were localized and found to have opposite orientations. The DNA fragment corresponding to the individual transposon TnA was isolated after the endonuclease S1 digestion of RP4::TnA molecules annealed under conditions favoring intramolecular renaturation. The attempts to transform the cells of Escherichia coli QD5003, HB101[pCRI] and JC7623 with the isolated transposon were unsuccessful. PMID- 6244210 TI - Alteration of the specificity of restriction endonucleases in the presence of organic solvents. AB - The specificity of XbaI, SalI, HhaI, PstI, BamHI and SstI is relaxed in the presence of an organic solvent, such as 20% glycerol or 8% dimethylsulfoxide (DMSO). This alteration, very pronounced in some cases, requires an excess of enzyme, varies from one kind of enzyme to another and is highly dependent on the pH, the ionic strength, the nature of the metallic cofactor and/or the presence of a second organic solvent. Preliminary data concerning XbaI and BamHI used under conditions where the relaxation of specificity is moderate, suggest that some of the new ("pseudo") sites correspond to shortened sequences derived from the normal recognition sequence cleaved under the standard conditions of the reaction. PMID- 6244211 TI - Construction of a SalI/PstI restriction map of spinach chloroplast DNA using low gelling-temperature-agarose electrophoresis. AB - The restriction endonucleases SalI and PstI cleave circular chloroplast DNA of spinach (Spinacia oleracea) into 12 and 10 fragments, respectively. The sum of the fragment sizes in each of the series is equivalent to the contour length of the molecule (about 95 Md). A physical map was constructed by sequential digestions using low-gelling-temperature agarose to avoid the necessity of extracting the fragments from the gel. The circular DNA molecule of spinach chloroplasts consists of two identical sequences (each about 15 Md) arranged as an inverted repeat separated by two single-copy regions of different sizes (about 52 and 13 Md). PMID- 6244212 TI - Stimulation of transcription of chromatin by specific small nuclear RNAs. AB - Small molecular weight nuclear RNAs (SnRNA) purified from the chromatin of SV40 transformed W138 human fibroblasts have been found to stimulate transcription of chromatin in homologous isolated nuclei as well as in nuclei of untransformed human and monkey cells. Stimulation in normal cell nuclei involves an increase in both initiation sites and rate of elongation of RNA chains. Fractionation of the SnRNA in polyacrylamide gradient slab gels revealed that the "active" RNA was 160 175 nucleotides in length. PMID- 6244213 TI - Identification and mapping of a 60 bp EcoRI fragment in the Dictyostelium discoideum ribosomal DNA. AB - We have re-examined the organization of the transcribed sequences in the ribosomal DNA repeat unit of Dictyostelium discoideum. In addition to the four EcoRI fragments previously reported, we have identified and cloned a fifth fragment which defines a small portion of the 25S ribosomal RNA. The fragment is 60 bp long and is located between the 1.5 kbp and the 3 kbp EcoRI fragments of the ribosomal DNA repeat unit. PMID- 6244215 TI - Plasmids containing many tandem copies of a synthetic lactose operator. AB - Up to 12 tandem copies of the lactose operator sequence AATTCCACATGTGGAATTGTGAGCGGATAACAATTTGTGG (3') GGTGTACACCTTAACACTCGCCTATTGTTAAACACCTTAA (5') have been cloned in the EcoRI site of plasmid pMB9. A 12-operator plasmid is about 8% operator by weight and represents a rich source of this DNA segment. A procedure for the rapid and convenient isolation of operator in mg quantities is presented. The lifetimes of complexes formed between repressor and oligo-operator plasmids increased with increasing numbers of tandem operators per plasmid. Evidence is presented indicating that only one tetrameric repressor molecule binds strongly to a segment of four (or fewer) tandem operators, but that two repressor molecules can be accommodated on segments containing at least six tandem operators. PMID- 6244214 TI - pMB9 plasmids bearing the Salmonella typhimurium his operon and gnd gene. AB - A plasmid containing the entire Salmonella typhimurium his operon was constructed from plasmid pM89 and an EcoRI fragment of phi 80 his imm lambda DNA. The recombinant pST41 also includes the glucose 6-phosphate dehydrogenase (gnd) gene and has one EcoRI endonuclease cleavage site in the integrated fragment. This plasmid served as a source for the construction of two additional plasmids, one carrying the OGDC-region of the his operon and the other a CBHAFIE segment of the his gene along with the gnd gene. The presence of the his operon in the constructed plasmids was confirmed by hybridization to S. typhimurium his RNA. The location of the gnd gene in the CBHAFIE fragment of the his gene was confirmed genetically: after transfection with the plasmid bearing the gnd gene, a gnd recipient gained the capacity to utilize gluconate as a sole carbon source. The DNAs of the three hybrid plasmids were analyzed by gel electrophoresis. By comparing the EcoRI endonuclease cleavage pattern of these three hybrid plasmids with the DNA cleavage pattern of phi 80 his imm lambda, phi 80 imm lambda and lambda phages, the EcoRI cleavage map of phi 80 his imm lambda was obtained. PMID- 6244216 TI - [Ultrastructural and clinical studies in "inclusion body myositis" (author's transl)]. AB - A non-hereditary slowly progressive neuromuscular disease occuring in a 39-year old male, consisting of an asymmetrical wasting of the muscles of the shanks, is reported. Neither clinical nor electromyographic criteria can safely distinguish whether a primary neurogenic or a primary myogenic process is causally involved. The initial rise in serum CPK-activity indicates a myopathic origin. The lightmicroscopic aspect of the muscle-biopsy shows a muscular atrophy which resembles a primary neurogenic pattern with grouped clusters of atrophic fibers as well as a myopathic or rather myositic tissue-pattern with randomly scattered atrophic fibers. In addition there are numerous vacuoles which are equivalent to concentric lamellae of dense material in electronmicroscopy. Numerous fibrillary inclusions as well in the cytoplasm as in the cell-nucleus correspond to typical alterations in the so-called "inclusion body myositis". The disease is critically discussed as a nosological entity among neuromuscular disorders. PMID- 6244217 TI - Amplification of hormone receptors by neonatal oxytocin and vasopressin treatment. AB - Newborn rats were treated once with 2 Units of vasopressin (VP) or oxytocin, respectively. At the age of 2 months and 1 year, respectively, the reactivity of isolated aortic strips to vasopressin and noradrenaline was tested. In young adults animals vasopressin pretreatment enhanced whilst oxytocin pretreatment decreased the responsiveness of aortic strips to VP. In elder specimens both types of pretreatment resulted in an increased late sensitivity to VP. The norepinephrine-sensitivity was higher in the young adults pretreated with oxytocin, whilst in the elder ones vasopressin-retreatment gave the same late effect. It could be established that the hormone excess produced in the neonatal age led to the "amplification" of hormone receptors and this alteration provided to be permanent. A compound which is similar to but not identical with the hormone--in our case, oxytocin--would elicit an alteration of a less unindirectional and permanent type; late sensitivity changes in both directions may occur. PMID- 6244218 TI - Stimulatory effects of gamma-aminohydroxybutyric acid (GABOB) on growth hormone, prolactin and cortisol release in man. AB - Healthy male volunteers injected subcutaneously with 200 mg L-GABOB showed no significant changes in plasma GH, prolactin and cortisol levels. On the other hand, an intrathecal injection of 300 mg D, L-GABOB to cerebrovascular patients caused significant increases in plasma GH, prolactin and cortisol levels at 60 min after injection. These results indicate that GABOB may elicit the secretion of GH, prolactin and ACTH via the central nervous system. PMID- 6244219 TI - Glucagon secretion in rats with islet cell tumors induced by streptozotocin. PMID- 6244220 TI - Effect of calcitonin on plasma cAMP in uraemic man. PMID- 6244221 TI - Galactosamine is an inducer of Gal genes in Saccharomyces cerevisiae. AB - In yeast cells galactosamine in concentrations of 0.1 1M partially inhibits the synthesis of RNA but has little effect on the protein synthesis. In vivo and in vitro studies show that galactosamine is metabolized in yeast to UDP-N acetylhexosamines but at a reduced rate, compared to the metabolism of galactose. The addition of galactosamine to growing yeast cells leads to the induction of the galactose pathway enzymes. Studies using different mutants in the galactose genes provide evidence that galactosamine is an inducer of the galactose structural genes in yeast. The same degree of induction of galactokinase and galactotransferase, found when galactose or galactosamine were used as inducers, supports the model of coordinated regulation in the expression of the structural genes for the galactose pathway enzymes in yeast. PMID- 6244222 TI - Input-output analysis of an IPFM neural model: effects of spike regularity and record length. PMID- 6244223 TI - Induced excitation and synchronization of nerve impulses in two parallel unmyelinated fibers. PMID- 6244224 TI - Serum antibodies to herpes simplex virus type 1 during active oral herpes infection. AB - Subjects with oral herpes lesions at the time of serum sampling had higher efficiency antibody (higher proportion of neutralizing antibody as determined by plaque reduction, compared with total antibody as detected by radioimmunoassay) to herpes simplex virus type 1 (HSV-1) than did subjects with no lesions at the time of serum sampling. These higher-efficiency sera also had higher antibody titers to structural components of herpes simplex virus type 1 than did the low efficiency sera. Absorption of high- and low-efficiency sera with purified herpes simplex virus type 1 particles removed all neutralizing antibody but not all antibody detected by radioimmunoassay. High-efficiency serum was depleted of more antibody to particulate antigen that was the low-efficiency serum, indicating that the high-efficiency serum contained a higher proportion of antibody to the virus particle. PMID- 6244225 TI - Cell-mediated immunity against herpes simplex induction of cytotoxic T lymphocytes. AB - The conditions required for the induction of both primary cytotoxic T lymphocytes (CTL) in vivo and secondary CTL in vitro against herpes simplex virus type 1 (HSV 1)-infected cells were defined. Primary CTL responses occurred only in mice exposed to infectious HSV-1. These responses, which were shown to be mediated by T lymphocytes, peaked at 1 week and had disappeared by 2 weeks after infection. The level of primary cytotoxicity was enhanced by treatment of mice with cyclophosphamide before infection. Secondary in vitro CTL responses were more pronounced and were induced by some forms of inactivated virus as well as by infectious HSV-1. Thus, both ultraviolet light- and glutaraldehyde-inactivated preparations of HSV-1 induced CTL, but heat-inactivated and detergent-extracted antigens failed to do so. The reasons for the differing efficiency of infectious and noninfectious HSV-1 for induction of CTL are discussed. PMID- 6244227 TI - Different susceptibilities of skin to type 1 and type 2 herpes simplex viruses in newborn rabbits. AB - Skin infections with type 1 herpes simplex virus (HSV-1) were compared with skin infections with type 2 virus (HSV-2). Five strains each of HSV-1 and HSV-2 were tested by injecting 10(3) 50% tissue culture infective doses of each strain subcutaneously into 1-day-old New Zealand white rabbits. All five strains of HSV- 2 produced severe skin lesions that resulted in wide dissemination of the infection to many organs, paralysis of the hind legs, and finally death. The virus could be isolated frequently from skin lesions, from various organs (liver, lungs, adrenal glands, brain, and eyes), and from circulating leukocytes and plasma. In contrast, all five strains of HSV-1 failed to produce significant skin lesions or dissemination of virus, only half of the skin lesions yielded HSV, and no virus could be isolated from the blood. These results indicate that HSV-1 dose not grow well in the skin of newborn rabbits and fails to disseminate, whereas HSV-2 is dermatotropic and disseminates readily to many organs by hematogenous routes. PMID- 6244226 TI - Effect of prostaglandins and cyclic adenosine 3',5'-monophosphate modulators on herpes simplex virus growth and interferon response in human cells. AB - Mechanisms whereby prostaglandins and other cyclic adenosine 3',5'-monophosphate (cAMP) modulators might enhance the growth of herpes simplex virus (HSV) in human skin fibroblasts were explored. Prostaglandins A1, B1, E1, E2, and F2 alpha, as well as isoproterenol, imidazole, carbamylcholine, and dibutyryl cAMP had no effect on HSV growth. On the other hand, the phosphodiesterase inhibitors 1 methyl-3-isobutylxanthine and theophylline delayed the growth, suppressed the cell-to-cell spread, but inhibited neither the adsorption nor the penetration of the virus. Although none of the cAMP-elevating reagents directly enhanced HSV growth, they were found to inhibit dose dependently the antiviral action of both type I and HSV antigen-induced human interferon preparations. Furthermore, these reagents suppressed the production of HSV antigen-induced interferon by immune human mononuclear leukocytes. These data support the hypothesis that prostaglandin elaboration in vivo could contribute to exacerbations of HSV infections by compromising the host's interferon defense system. PMID- 6244228 TI - Immunosuppressive effect of murine cytomegalovirus. AB - Murine cytomegalovirus suppressed the ability of spleen cells to respond to mitogens in vitro. The degree of suppression was proportional to the multiplicity of infection. This effect could not be explained by cytolysis of lymphocytes, an alteration in the kinetics of the response to mitogen, or a direct competition between virions and mitogen molecules for cell-surface receptors. Nor was it due to simple contact between cell and virus, since ultraviolet-inactivated murine cytomegalovirus failed to suppress the response to mitogens. Reconstitution experiments were performed which involved mixing various combinations of infected and uninfected macrophages and lymphocytes. Under these conditions, it was found that the infected macrophages and lymphocytes. Under these conditions, it was found that the infected macrophages had an impaired capacity to mediate the response ot T lymphocytes to concanavalin A. This suggests that murine cytomegalovirus may cause immunosuppression indirectly by interfering with macrophage function. PMID- 6244229 TI - Cardiac scan in massive myocardial calcification. PMID- 6244230 TI - Myeloid body associations in the frog pigment epithelium. AB - Myeloid bodies are found in the retinal pigment epithelium of certain vertebrate species. They are organized structural forms of the smooth endoplasmic reticulum which are usually seen as stacks of flattened, smooth saccules having a circular or lens-shaped configuration. Our findings in the frog Rana pipiens suggest that changes occur in the structure of the myeloid bodies which are related to the phase of the diurnal lighting cycle. At certain times, the myeloid bodies are found closely associated with other cytoplasmic organelles, notably the nucleus and oil droplet. In addition these associations can be induced by incubation of the isolated eyecup in the presence of guanosine 3',5'-monophosphate. PMID- 6244231 TI - Sodium-potassium--dependent ATPase. II. Cytochemical localization during the reversal of galactose cataracts in rat. AB - The importance of enzyme Na-K-ATPase in the development of galactose-induced cataractogenesis is now well realized. In our recent studies we reported decreased level of activity of this enzyme with an increased duration of galactose feeding and the induced alterations in rat ocular lens. Our approach was to determine the level of Na-K-ATPase activity by ultrastructural cytochemical analysis of lenses and spectrophotometric analysis of the incubating media used for cytochemical localization as described by Ernst. Using these approaches, we have determined the activity level of this enzyme during the reversal phase of the galactose-induced injury to the lens. Our findings are presented in this report and show that the activity of Na-K-ATPase recovers rapidly and attains the normal level when the animals were transferred to Rat Chow diet after the establishment of mature cataracts resulting from galactose feeding. This study supports the previous biochemical and morphological findings that partial reversal of galactose-induced cataractous lens occurs upon discontinuation of feeding of cataractogenic agent galactose. PMID- 6244232 TI - Human urologic cancer cell lines. PMID- 6244233 TI - Identification of Bulgarian strain 258 of enterovirus 71. AB - In 1975 in Bulgaria a severe epidemic of central nervous system (CNS) disease occurred. Clinically, histopathologically, and epidemiologically the cases resembled poliomyelitis, aseptic meningitis, meningoencephalitis, and, in some cases, encephalomyocarditis. About 21% of the 700 reported cases developed paralysis, 44 with fatal outcome [ref. 1]. In 65 cases, 92 strains of enterovirus of the same serologic type were isolated: 38 strains from the CNS, 10 from mesenteric lymph nodes and tonsils, and 44 from feces [ref. 1,2]. A typical representative strain, No. 258, isolated from the spinal cord of a 3-month-old baby who died on the 5th day of disease with signs of focal polioencephalitis, was selected for intensive study. Cross-neutralization tests established the antigenic identity of the Bulgarian 258 strain (Stanchev) with American strains of enterovirus type 71 (BrCr and JaFr strains) and Swedish strains of the same type (Nos. 52343, 52500, and 6041). From its biological [ref. 1,2], physicochemical [ref. 3], and antigenic properties, the etiological agent of this large epidemic can be classified as a member of enterovirus type 71, one of the most highly pathogenic of the recently recognized enteroviruses. PMID- 6244234 TI - NC37-R1 Epstein-Barr virus (EBV): a possible recombinant between intracellular NC37 viral DNA and superinfecting P3HR-1 EBV. AB - The NC37-R1 cell line, established after transformation of human cord blood lymphocytes with Epstein-Barr virus (EBV) recovered from P3HR-1 superinfected NC37 cells, spontaneously produces viral particles with transforming but without early antigen-inducing properties. Progeny virus of NC37-R1 has retained its biological characteristics of spontaneous virus release and transformation up to four cycles of transformation at present. Analysis of purified NC37-R1 virion DNA, after cleavage with restriction endonuclease Hind III and comparison of its fragments with P3HR-1 EBV as well as intracellular NC37 viral DNA using the blot hybridization technique, suggests that NC37-R1 originates from a recombination between superinfecting P3HR-1 and endogenous NC37 EBV DNA. PMID- 6244235 TI - Host-induced virus modification of murine hepatitis virus: changes in thermal stability. AB - Serial tissue culture passage of two cold-sensitive mutants of murine hepatitis virus altered the thermal stability of one mutant. This phenomenon occurred in only one of the continuous cell lines tested and was reversible by multiple passages in a cell line that does not alter thermal stability. The effect was cumulative with passage and was segregated from the cold-sensitive marker. PMID- 6244236 TI - Detection of B-tropic endogenous type-C virus in viral isolates originating from induced BALB/K-3T3 cells. AB - Isoelectric focusing (IEF) analysis of class I endogenous type-C virus induced by iododeoxyuridine treatment of BALB/K-3T3 cells revealed, in addition to the major variant of the p30 polypeptide, which has an isoelectric point of 6.1 (pI 6.1 isop30), a minor isop30 with a pI of 5.6. This value was also found for a prototype BALB/c B-tropic endogenous virus isolate. The pI 5.6 isop30 of the N tropic isolate was amplified by long-term virus replication in B-type mouse cells, and comparative IEF and XC-assay data suggest that it may correspond to a B-tropic subpopulation which has not yet been detected in vitro in mouse cells of embryonic origin. PMID- 6244237 TI - Improvement of enterovirus neutralization by treatment with sodium deoxycholate or chloroform. AB - Enterovirus strains which could be neutralized only partially or not at all by specific antiserum were readily accessible to the antibodies after treatment with sodium deoxycholate or chloroform. The latter treatment is simple and can be performed with crude virus suspensions of low titer. The method was particularly successful for routine typing of enterovirus 71 and coxsackievirus types A7 and A16. PMID- 6244238 TI - Inhibition of cytomegalovirus late antigens by phosphonoformate. AB - Phosphonoformate (PFA) at a concentration of 500 muM and higher completely inhibited the replication of cytomegalovirus (CMV) in cell culture. 50% inhibition was obtained at a concentration of muM PFA. Early nuclear CMV antigens appeared uninhibited, but the formation of nuclear inclusion bodies, late cytoplasmic antigens, Fc-receptors and CPE were all inhibited by PFA. No visible cell toxicity was noted at the PFA concentrations and exposure times used. PMID- 6244239 TI - Acycloguanosine treatment of herpesvirus infections in footpads and nervous tissue of normal and immunosuppressed mice. AB - Treatment of herpes simplex virus type 1 (HSV-1)-infected mice with acycloguanosine resulted in significantly fewer virus isolates from nervous tissues than from tissues of untreated animals. Acycloguanosine also significantly reduced the mean titers of HSV-1 recovered from the footpads of drug-treated animals. The anti-herpetic activity of acycloguanosine was observed in both normal and immunosuppressed mice. PMID- 6244240 TI - Distribution of sequences homologous to the DNA of herpes simplex virus, types 1 and 2, in the genome of pseudorabies virus. AB - The distribution of related sequences between the genomes of pseudorabies virus (PRV) and herpes simplex virus, types 1 (HSV-1) and 2 (HSV-2), was determined. Approximately 7% of the sequences in PRV are shared by HSV-1 and HSV-2 DNAs. By means of the Southern blot technique, it was found that the homologous sequences are not sequestered in one region but are distributed throughout the PRV genome. HSV-1 and HSV-2 have the greatest homology with the long unique region of PRV DNA and the least with the inverted repeat regions of the molecule. HSV-1 DNA also has few sequences homologous to the short unique region of the PRV genome; HSV-2 DNA hybridizes well to this region. There was no homology of HSV-1 or HSV-2 DNAs with the extreme ends of the inverted repeat regions of PRV DNA. PMID- 6244241 TI - Lack of association between the elevation of adenosine 3',5'-cyclic monophosphate and the potentiation of the interferon-induced antiviral state by noradrenaline in normal and tumoral rat cells. AB - Rat interferon (IF) induced a moderate and persistent elevation of adenosine 3',5'-cyclic monophosphate (cAMP) after 6 h of contact with rat embryo fibroblasts (REFs), whereas in rat glial tumoral c6 cells IF did not enhance cAMP. Noradrenaline potentiated the antiviral state of REFs treated for 2 h or more with IF and increased cAMP in these cells, but it did not potentiate the IF induced antiviral state of C6 cells. However, as the control cells, IF-treated C6 cells responded to catecholamines by a 100-fold or more increase in cAMP. This suggested that cAMP was not primarily involved in the establishment of the antiviral state. PMID- 6244242 TI - Reduction of cell surface fibronectin (LETS protein) correlates with tumorigenicity of hamster fibroblasts transformed by herpes simplex virus type2. AB - A series of herpes simplex virus type 2 (HSV-2)-transformed hamster cells has been examined using the technique of lactoperoxidase-catalyzed cell surface protein iodination. The amount of cell surface fibronectin (LETS protein) was reduced after HSV-2 transformation, and this reduction correlated with increased tumor-forming ability. PMID- 6244243 TI - Fragility of the rhinovirus type 14 genome to incubation at 60 degrees. AB - Rhinovirus type 14 (RV14) genomic RNA, but not mengovirus or coxsackievirus B3 genomic RNA, fragmented to acid-insoluble RNA species during incubation in aqueous buffers at 60 degrees. Incubation of RV14 genomic RNA in high concentrations of dimethyl sulfoxide at 60 degrees did not result in fragmentation, suggesting that fragmentation was not a result of pre-existing nicks. RV14RNA that was treated with proteinase K prior to incubation at 60 degrees did not undergo fragmentation. The association of protein(s) with RV14 virion RNA was demonstrated by radiolabeling with amino acids. These results showed that protein(s) associated with RV14 genomic RNA was in some manner responsible for fragmentation of the RNA during incubation at 60 degrees. PMID- 6244244 TI - PAS-positive reaction of phenolic inclusions in plant cell vacuoles. AB - The experimental data presented show that positive reaction of phenolic inclusions in the PAS test may be caused by the presence of phenolic glycosides and/or certain non-glycosidic phenols, namely flavan-3,4-diols. These both possibilities and their respective importance under conditions of conventional histological procedures are discussed. The findings emphasize the need for extreme care in interpreting the results of the PAS reaction applied to plant material. PMID- 6244245 TI - Solid tumors in children. PMID- 6244246 TI - Expectant parents' classes: an alternative environment for learning health maintenance. PMID- 6244247 TI - The use of the seminar as a teaching technique with senior undergraduate nursing students. PMID- 6244248 TI - Physical assessment skills in the curriculum: a pilot project & follow-up. PMID- 6244249 TI - Learning from sensations. PMID- 6244250 TI - Teaching clinical research: idealism versus realism. PMID- 6244251 TI - Does integrated content lead to integrated knowledge? PMID- 6244252 TI - Student peer evaluation: a successful adaptation for observed home visits. PMID- 6244253 TI - Women in nursing and academic tenure. PMID- 6244254 TI - How to solve a math problem. PMID- 6244255 TI - A broader perspective on teaching pediatric nursing: graduate students' reactions. PMID- 6244256 TI - Peer analysis of interpersonal responsiveness and plan for encouraging effective reshaping. PMID- 6244257 TI - Influence of dietary fiber, protein and zeolite on zeralenone toxicosis in rats and swine. PMID- 6244258 TI - The activity in vitro and in vivo of a new imidazole antifungal, ketoconazole. PMID- 6244259 TI - Hormone receptors. PMID- 6244260 TI - Activation of rabbit muscle fructose 1,6-bisphosphatase by histidine and carnosine. AB - Histidine and its derivatives increased rabbit muscle fructose 1,6-bisphosphatase activity at neutral pH with positive cooperativity. In the presence of histidine and carnosine the optimum pH shifted from pH 8.0 to 7.4. The cooperative response of the enzyme to AMP and fructose 1,6-bisphosphate was observed in the presence of the histidine derivatives. Of a number of divalent cations tested, only Zn2+ was found to be an effective inhibitor of enzyme activity at low concentrations. The kinetic data suggested that Zn2+ acted as inhibitor as well as activator for the enzyme activity; a high affinity binding site was associated with Ki of approximately 0.5 microM Zn2+ and a catalytic site was associated with Km of approximately 10 microM Zn2+. Rabbit muscle fructose 1,6-bisphosphatase bound 4 equivalents of Zn2+/mol, presumably 1 per subunit, in the absence of fructose 1,6 bisphosphate. Two equivalents of Zn2+/mol bound to the enzyme were readily removed by dialysis or gel filtration in the absence of a chelating agent. The other two equivalents of Zn2+/mol were removed by histidine and histidine derivatives of naturally occurring chelators with concomitant increase in activity. PMID- 6244261 TI - Amino acid sequence of cytochrome c from rice. AB - The amino acid sequence of cytochrome c purified from rice, Oryza sativa L., was determined. The complete amino acid sequence of rice cytochrome c is as follows: Ac-Ala-8-Ser-Phe-Ser-Glu-Ala-Pro-Pro-Gly1-Asn-Pro-Lys-Ala-Gly-Glu-Lys-Ile-Phe10 Lys-Thr-Lys-Cys-Ala-Glx-Cys-His-Thr-Val20-Asp-Lys-Gly-Ala-Gly-His-Lys-Glx-Gly Pro30-Asx-Leu-Asx-Gly-Leu-Phe-Gly-Arg-Glx-Ser40-Gly-Thr-Thr-Pro-Gly-Tyr-Ser-Tyr Ser-Thr50-Ala-Asp-Lys-Asn-Met-Ala-Val-Ile-Trp-Glx60-Glx-Asx-Thr-Leu-Tyr-Asp-Tyr Leu-Leu-Asn70-Pro-TML-Lys-Tyr-Ile-Pro-Gly-Thr-Lys-Met80-Val-Phe-Pro-Gly-Leu-TML Lys-Pro-Glx-Glx90-Arg-Ala-Asp-Leu-Ile-Ser-Tyr-Leu-Lys-Glu100-Ala-Thr-Ser (Ac = acetyl group, TML = epsilon-N-trimethyllsine). The primary structure of rice cytochrome c was found to be homologous with those of other plant cytochromes c reported so far; it possesses general features common to plant cytochromes c, and all the invariant residues characterized in dicotyledonous cytochromes c are also conserved in the sequence of rice cytochrome c, as well as those of other monocotyledonous cytochromes c. The distinctive features of rice cytochrome c are a high content of proline residues, their unique locations in the sequence and the presence of a serine residue at position 96. PMID- 6244262 TI - A spin-label study of the effects of drugs on calcium release from isolated sarcoplasmic reticulum vesicles. AB - The effects of caffeine, thymol, and procaine on calcium release from fragmented sarcoplasmic reticulum (FSR) from rabbit skeletal white muscle were investigated by the spin label method at the organellar level. Two thiol-directed spin labels, 4-maleimide-2,2,6,6-tetramethylpiperidinooxyl and 4-(2-iodoacetamide)-2,2,6,6 tetramethylpiperidinooxyl, were used for the labeling of SR proteins. The ratio (W/S) of the weakly (W) and strongly (S) immobilized ESR signals was measured for the maleimide and iodoacetamide labeled FSR. The two labels gave different W/S values, which means that the two labels report conformational changes at different loci of SR proteins. The dependences of the W/S ratios on the concentration of the drugs showed that conformational changes of SR proteins induced by these drugs are not the same. From measurements of the distribution of 5-doxyldecanoic acid methylester between the lipid and water phases, it was found that the conformational changes of the SR proteins caused by thymol or procaine induced a disorder in local regions of the phospholipid bilayers of FSR, while such disordering was not induced by caffeine. On the other hand, caffeine and thymol showed definite effects on calcium release from FSR, while procaine did not. These results indicate that the effects of the drugs on the protein conformations can be well characterized at the organellar level by means of the spin label technique and that some specific changes in the conformations of SR proteins are necessary for calcium release from FSR. PMID- 6244263 TI - Effect of different growth media on the synthesis of carbohydrate-Binding protein from Dictyostelium discoideum NC-4. AB - The carbohydrate-binding protein, discoidin, was synthesized from Dictyostelium discoideum NC-4 grown on a Bacto peptone (Difco) containing medium together with bacteria. When the cells were transferred by serial passage to a Proteose peptone (Daigo)-containing medium, the productivity of discoidin was reduced to a negligible amount, but the cells formed aggregates, and another protein which binds with Sepharose 4B was detected by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. We conclude that discoidin synthesis is already regulated during growth, and even when the amount of this protein is nil or negligible, the cells still retain aggregate-forming ability. PMID- 6244264 TI - Mouse spleen cell nuclear protein kinases and the stimulating effect of dsDNA on NHP phosphorylation by cyclic AMP-independent protein kinase in vitro. AB - cAMP-dependent (designated as enzyme I, about 68,000 daltons) and cAMP independent protein kinase (designated as enzyme II, about 45,000 daltons) have been partially purified from the nuclei of mouse spleen cells. Both kinases phosphorylated calf thymus histones as well as non-histone proteins (NHP) and required Mg2+ (8 mM) or Mn2+ (2 mM) for maximal activity. NEM (0.5 mM), which is an inhibitor of SH-enzymes, inhibited the histone phosphorylating activity of enzyme II by more than 90%, whereas it inhibited the activity of enzyme I by less than 10%. Moreover, the activity of enzyme II was more sensitive to high temperature than that of enzyme I. Non-histone protein (CM-III protein) served as a more effective substrate for enzyme II than histones; the Km value for CM-III protein was 34.4 micrograms/ml whereas that for histone H2a (14,300 daltons) was 155 micrograms/ml (1.08 x 10(-5) M). CM-III protein phosphorylation by enzyme II in vitro was greatly stimulated by the addition of dsDNA, but not by single stranded DNA or bacterial ribosomal RNA. However, the phosphorylation of CM-III protein by enzyme I was less than 50% of that of histones, and there was no stimulatory effect. SDS-gel electrophoresis showed that two distinct NHPs (about 13,000 and 19,000 daltons) prepared from calf thymus chromatin were preferentially phosphorylated by enzyme II in vitro in the presence of dsDNA. This finding suggests that these two NHPs may be specific phosphate acceptors of cAMP-independent protein kinase (enzyme II) in the nuclei of mouse spleen cells. PMID- 6244266 TI - Purification and identification of the factor capable of converting Ca2+-ATPase into Mg2+-ATPase present in Rhodospirillum rubrum chromatophores. PMID- 6244265 TI - Myeloperoxidase of the leukocyte of normal blood. Nature of the prosthetic group of myeloperoxidase. AB - The absorption spectra of alkaline pyridine hemochrome of myeloperoxidase in its native, acid, and modified forms were similar to those of heme a, and the molar extinction coefficient of myeloperoxidase heme was very similar to that of heme a, assuming that myeloperoxidase contains only one heme. The anaerobic titration of myeloperoxidase with dithionite showed that one electron was consumed per molecule of the enzyme for its conversion to its reduced form. The EPR spectrum of myeloperoxidase indicated that the enzyme contains both high-spin heme and non heme iron. Carbonyl reagents, such as borohydride, hydrazine, and benzhydrazide, reacted with myeloperoxidase, causing blue shifts in its absorption spectrum. The heme was labeled with a tritium of boro[3H]hydride, suggesting that the reagents reacted with a formyl group on the porphyrin ring of the myeloperoxidase heme. When hydrazine was added to cyanide complex I of myeloperoxidase the complex was converted to the hydrazine-enzyme compound. Myeloperoxidase reacted with bisulfite to form a compound with an absorption spectrum similar to that of cyanide complex I. Borohydride-treated myeloperoxidase formed only one cyanide complex, while the native enzyme formed two different cyanide complexes, I (Kd = 0.3 muM) and II (approximate Kd = 0.1 mM). The EPR spectrum indicated that cyanide complex I of myeloperoxidase still contained high-spin heme. The results suggested that cyanide complex I and the bisulfite compound of myeloperoxidase were adducts between the nucleophilic reagents and the formyl group of myeloperoxidase heme. Based on these results, we concluded that one of the two iron atoms in a myeloperoxidase molecule exists in a formyl-heme moiety similar to heme a and the other exists as a non-heme iron. PMID- 6244267 TI - Effect of phospholipid substitution on the mobility of protein-bound spin labels in sarcoplasmic reticulum. AB - The influence of phospholipid environment upon the mobility of spin labels covalently bound to the Ca2+-transport ATPase (ATP phosphohydrolase [EC 3.6.1.3]) was studied by electron spin resonance spectroscopy in native and reconstituted sarcoplasmic reticulum membranes. Fragmented sarcoplasmic reticulum of rabbit skeletal muscle was covalently labeled with maleimide spin-labels of different chain length or with 4-(2-iodoacetamido)-2,2,6,6-tetramethylpiperidinooxyl, and the phospholipids were exchanged for dipalmitoylphosphatidylcholine or dioleoylphosphatidylcholine. With short-chain maleimide or iodoacetamide spin labels, the spectrum of the protein-bound label reflected the change in microenvironment caused by replacement of endogenous phospholipids with dipalmitoylphosphatidylcholine as a decrease in mobility. In contrast, after labeling with long-chain maleimide derivatives, there were no noticeable differences in the spectra before and after substitution with dipalmitophatidylcholine. Replacement of endogenous phospholipids with dioleoylphosphatidylcholine did not affect the spectra. The data indicate that increased viscosity in the environment of Ca2+-transport ATPase produced by replacement of sarcoplasmic reticulum lipids with dipalmitoylphosphatidylcholine reduces the mobility of short-chain maleimide spin labels covalently attached to the Ca2+-transport ATPase polypeptide. PMID- 6244268 TI - Calcium-activatable phosphodiesterase and calcium-dependent modulator protein in transplantable hepatoma tissues. PMID- 6244269 TI - Partial purification and properties of the amino-terminal amino acid-acetylating enzyme from hen's oviduct. AB - By using the synthetic peptide ACTH1-24 as a model substrate, an enzyme that may be involved in the amino-terminal acetylation of certain proteins and growing nascent polypeptide chains has been found in hen's oviduct. It was partially purified by a four-step procedure comprising extraction from the homogenates, ammonium sulfate fractionation, chromatography on a column of QAE-Sephadex A-50, and gel filtration on a Sepharose 6B column. An enzyme preparation purified about 40-fold from the homogenates transferred the acetyl group from acetyl coenzyme A preferentially to the amino-terminal amino acids of several ACTH-related peptides at an optimum pH of around 7.2. This occurred to different extents depending on the peptide length and on the nature of the amino-terminal residue. The molecular weight of the enzyme was estimated to be approximately 250,000 by gel filtration. PMID- 6244270 TI - Purification and enzymatic characterization of three endoDNase isoenzymes from Physarum polycephalum. AB - Three alkaline DNases, A, B, and C, with preference for the digestion of double stranded DNA (dsDNA) were partially purified from microplasmodia of Physarum polycephalum. They were very similar but differed in their isoelectric points. These were pH 5.8 for DNase A, 7.1 for DNase B, and 9.1 for DNase C. All three enzymes consisted of a single polypeptide chain with a molecular weight of 16,000 to 17,000, which readily formed high molecular weight complexes with low enzyme activity. These complexes could be reversibly dissociated by urea, and DNase activity was quantitatively reactivated. The DNases hydrolyzed the substrate DNA by an endonucleolytic mechanism which gave 5'-phosphorylated products. Divalent cations, MnCl2 or MgCl2, were essential for enzyme activity at the optimum pH of approximately 8.5 and at low ionic strength. The optimal conditions of pH, buffer, divalent cations and ionic strength and the extent of inhibition by salt, phosphate ions or urea differed slightly but significantly between the different isoenzymes. PMID- 6244271 TI - Isolation of calmodulin from the protozoan, Tetrahymena pyriformis, by the use of a tubulin-Sepharose 4B affinity column. AB - We developed a simple new method for the isolation of calmodulin, a ubiquitous Ca2+-binding protein, by using tubulin-Sepharose 4B column chromatography, and succeeded in rapid isolation of calmodulin from Tetrahymena pyriformis. The procedure was also shown to be successfully applicable to the isolation of calmodulins from starfish ovary, porcine brain, and monkey brain and, therefore, may be of general use for the rapid isolation of calmodulin. PMID- 6244272 TI - Electron paramagnetic resonance and optical absorption spectrum of the pentacoordinated ferrihemoproteins. PMID- 6244273 TI - Comparison of potential nuclear precursors for prolactin and growth hormone messenger RNA. AB - Recombinant DNA plasmids containing the coding sequence for rat prolactin or rat growth hormone have been used to investigate the presence of possible precursors for prolactin and growth hormone mRNA. Cytoplasmic and nuclear RNA was prepared from either rat pituitaries or fromthe GC pituitary cell line. RNA was electrophoresed on agarose gels containing methylmercury hydroxide and then transferred to diazobenzyloxymethyl paper. The paper was then hybridized to prolactin or growth hormone recombinant DNA probes labeled in vitro with 32P. The prolactin probe hybridized to RNA species of 7.0, 6.4, 3.8, 1.7, and 1.0 kilobases in nuclear RNA and only to a 1.0-kilobase species in cytoplasmic RNA. Hybridization with a growth hormone probe demonstrated nuclear RNA species of 6.7, 5.6, 2.3, and 1.0 kilobases. These findings demonstrate the presence of multiple species of prolactin and growth hormone RNA which are larger larger than the mature cytoplasmic mRNAs. The large nuclear RNAs are likely precursors for prolactin and growth hormone mRNA. PMID- 6244274 TI - Epinephrine regulation of skeletal muscle glycogen metabolism. Studies utilizing the perfused rat hindlimb preparation. AB - Studies of rat skeletal glycogen metabolism carried out in a perfused hindlimb system indicated that epinephrine activates phosphorylase via the cascade of phosphorylation reactions classically linked to the beta-adrenergic receptor/adenylate cyclase system. The beta blocker propranolol completely blocked the effects of epinephrine on cAMP, cAMP-dependent protein kinase, phosphorylase, and glucose-6-P, whereas the alpha blocker phentolamine was totally ineffective. Omission of glucose from the perfusion medium did not modify the effects of epinephrine. Glycogen synthase activity in control perfused and nonperfused muscle was largely glucose-6-P-dependent (-glucose-6-P/+glucose-6-P activity ratios of 0.1 and 0.2, respectively). Epinephrine perfusion caused a small decrease in the enzyme's activity ratio (0.1 to 0.05) and a large increase in its Ka for glucose-6-P (0.3 to 1.5 mM). This increase in glucose-6-P dependency correlated in time with protein kinase activation and was totally blocked by propranolol and unaffected by phentolamine. Comparison of the kinetics of glycogen synthase in extracts of control and epinephrine-perfused muscle with the kinetics of purified rat skeletal muscle glycogen synthase a phosphorylated to various degrees by cAMP-dependent protein kinase indicated that the enzyme was already substantially phosphorylated in control muscle and that epinephrine treatment caused further phosphorylation of synthase, presumably via cAMP dependent protein kinase. These data provide a basis for speculation about in vivo regulation of the enzyme. PMID- 6244275 TI - Spectroscopic studies of the cAMP binding sites of the regulatory subunits of types I and II protein kinase. PMID- 6244276 TI - Stoichiometry of cAMP and 1,N6-etheno-cAMP binding to protein kinase. PMID- 6244277 TI - Effects of epsilon-pyridoxyllysine and related compounds on liver and brain pyridoxal kinase and liver pyridoxamine (pyridoxine) 5'-phosphate oxidase. PMID- 6244278 TI - Adenosine kinase from L1210 cells. Purification and some properties of the enzyme. PMID- 6244279 TI - A non-histone chromatin protein that is a specific phosphate acceptor of nuclear cAMP-independent protein kinase from mouse spleen cells. AB - A non-histone chromatin protein (NHCP), which is specifically phosphorylated by a nuclear cAMP-independent protein kinase from mouse spleen cells in vitro, has been purified from calf thymus chromatin. SDS-polyacrylamide gel electrophoresis shows that the molecular weight of the purified NHCP (single peptide) is 13,000. This peptide consists of 14 amino acid residues and has high serine content (17.9%). However, no methionine, proline, or half-cysteine have been detected. The NHCP is a basic protein (isoelectric point, approximately 9.0), although it has high acidic amino acid content (26.2%). This protein serves as the most effective phosphate acceptor for the kinase in vitro when compared with other chromatin proteins such as histones; the Km value of the kinase for the NHCP is 3.65 x 10(-6) M, whereas that for histone H2a (Mr = 14,000) is 1.08 x 10(-5) M. The present finding that the NHCP phosphorylation by the kinase in vitro is remarkably stimulated by double-stranded DNA but inhibited by whole histone or histone H2a suggests that the phosphorylation may be controlled by both double stranded DNA and histone H2a. PMID- 6244280 TI - Purification and properties of liver fructose 1,6-bisphosphatase from C57BL/KsJ normal and diabetic mice. PMID- 6244281 TI - Mossbauer and EPR studies of desulforedoxin from Desulfovibrio gigas. PMID- 6244282 TI - Thyroid hormone nuclear receptor levels are influenced by the acetylation of chromatin-associated proteins. AB - The thyroid hormone receptor is a chromatin-associated protein which appears to mediate the actions of the thyroid hormones in mammalian cells. Unlike steroid hormone receptors, a cytoplasmic form of the receptor has not been identified, and the factors which govern the nuclear concentrations of the receptor are poorly understood. Using cultured GH1 cells, a rat pituitary cell line, we having previously demonstrated that thyroid hormones reduces the concentration of its receptor by a mechanism which involves the association of the ligand with the receptor binding site (Samuels, H.H., Stanley, F., and Shapiro, L.E. (1977) J. Biol. Chem. 252, 6052-6060). In this study, we demonstrate that n-butyrate and other aliphatic carboxylic acids elicit a reduction of thyroid hormone nuclear receptor levels without altering total cell protein synthetic rates. In contrast, the nuclear association and total cell level of the glucocorticoid receptor is not altered by n-butyrate. Evidence is presented that the aliphatic carboxylic acid-mediated reduction of thyroid hormone nuclear receptor levels is secondary to the inhibitory effect of these compounds on chromatin-associated deacetylases which is reflected as an increase in the acetylation of the nucleosome core histones. Isokinetic gradient centrifugation of chromatin solubilized from GH1 cell nuclei by micrococcal nuclease indicates that the receptor exists as a form associated with high molecular weight chromatin, as a 12.5 S form that sediments slightly faster than the bulk of the mononucleosomes, and as a 6.5 S form which appears to remain associated with low molecular weight chromatin components. Exclusive of the receptor associated with the high molecular weight chromatin, the 6.5 S form represents 80% and the 12.5 S form 10% of the receptor resolved in the gradient. n-Butyrate decreases both forms to the same degree suggesting that they are generated from the same "entity" of chromatin structure. Studies on the reappearance of receptor after restoration of the chromatin to the "normal" acetylated state are consistent with a model in which the affinity of chromatin for newly synthesized receptor is diminished in the "hyperacetylated" state. PMID- 6244283 TI - Structural comparison of two nontandemly repeated yeast glyceraldehyde-3 phosphate dehydrogenase genes. AB - A hybrid plasmid (pgap63) was isolated which contains a second yeast glyceraldehyde-3-phosphate dehydrogenase structural gene. The complete nucleotide sequence of this gene was determined and compared with the primary structure of a yeast glyceraldehyde-3-phosphate dehydrogenase gene (pgap49) which was reported previously (Holland, J.P., and Holland, M.J. (1979) J. Biol. Chem. 254, 9839 9845). Based on the restriction endonuclease cleavage maps of the isolated segments of yeast DNA which contain these genes, the two genes are nontandemly duplicated. Greater than 94% of the nucleotides within the coding regions of these genes are homologous and the polypeptides encoded by the two structural genes differ by only 15 amino acid residues. Both genes have the same, highly biased, codon usage pattern and neither contains intervening sequences. Approximately 100 nucleotides adjacent to the ATG initiation codons and 130 nucleotides beyond the TAA termination codons are greater than 70% homologous. Structures within the flanking sequences of the genes which are potentially relevant to transcriptional and translational control are described. Several sequences (8 to 15 nucleotides in length) are repeated in both the 5' and 3' flanking sequences of the genes in a noninverted fashion. Finally, a rapid procedure for the isolation of spontaneous deletions within hybrid plasmid DNAs is described, as is the isolation of a structural gene deletion in pgap49. PMID- 6244284 TI - Purification and characterization of mitochondrial cytochrome P-450 associated with cholesterol side chain cleavage from bovine corpus luteum. AB - The cytochrome P-450scc associated with cholesterol side chain cleavage was purified to homogeneity from bovine corpora lutea mitochondria by fractional column chromatography on various ion exchange columns and on a heptyl-Sepharose hydrophobic column. Purification was 75-fold, recovery was 10%, the specific concentration of P-450 was about 15 nmol/mg of protein, and the specific content of heme was 16 nmol/mg of protein. The purified protein migrated as a single band on native polyacrylamide gel electrophoresis and as a single major band with an insignificant minor band (less than 1%) on SDS-gel electrophoresis. The molecular weight of the major band was 48,000. The optical absorption spectra of the preparation exhibited Soret maxima at 416, 416, and 450 nm for the oxidized form, reduced form, and CO-reduced complex, respectively. Apparently homogeneous enzymes were purified with a molecular weight 2, 4, 6, and 8 times the molecular weight of the single unit. The enzymatic activities of the reconstituted systems under optimal conditions were 16 nmol of cholesterol cleaved/mol of P-450. The 2 unit protein was about 5% as active either because it is an incomplete portion of the natural enzyme or because the molecular environmental conditions were not optimal. No differences in biophysical characteristics between cytochrome P 450sec from corpus luteum and adrenal sources could be identified. PMID- 6244285 TI - Construction of a recombinant bacterial plasmid containing pro-alpha 1(I) collagen DNA sequences. AB - A partially purified mRNA preparation enriched for chick collagen messenger RNA activity was used as template for the synthesis of double stranded cDNA. The cDNA was ligated into the HindIII site of the plasmid vector pBR322 and used to transform Escherichia coli x1776. One plasmid with an 800-base pair insert was shown to contain DNA sequences corresponding to Type I pro-alpha 1 collagen. PMID- 6244286 TI - An investigation of ordered complex formation with chemically modified fragments of cytochrome c. The role of heme iron. PMID- 6244287 TI - Quantitation of hemoproteins in rat small intestinal mucosa with identification of mitochondrial cytochrome P-450. PMID- 6244288 TI - The identification of extrahepatic "glucokinase" as N-acetylglucosamine kinase. AB - Several research groups have reported the presence of a high Km glucokinase (ATP:D-glucose 6-phosphotransferase, EC 2.7.1.2) in tissues other than adult liver. As shown in this report, protein fractions catalyzing glucose phosphorylation only at high substrate concentrations (100 mM) are indeed found in bovine spleen, rat kidney, human placenta, and newborn rat liver. However, the study of substrate specificities and Michaelis constant values showed that those fractions could be better described as N-acetylglucosamine kinase (ATP:acetamide 2-deoxy-D-glucose-6-phosphotransferase, EC 2.7.1.9) which, in addition to N acetylglucosamine (Km = 0.066 mM), can also phosphorylate glucose although with very high Km values (370 mM). Furthermore, a homogeneous preparation from bovine spleen was able to phosphorylate both N-acetylglucosamine and glucose. An immune serum against bovine spleen N-acetylglucosamine kinase did not cross-react with purified hexokinases or with glucokinase from rat. However, it was able to remove the putative "glucokinases" from extracts of rat kidney, newborn rat liver, and one of two electrophoretic bands of liver "glucokinase." It is proposed that any report of extrahepatic glucokinase should explicity rule out N-acetylglucosamine kinase as the enzyme being described. PMID- 6244289 TI - Critical controls in the evaluation of cAMP-dependent protein kinase activity ratios as indices of hormonal action. AB - Measurement of the cAMP-dependent protein kinase "activity ratio" was introduced by Corbin et al. (Corbin, J.D., Soderling, T.R., and Park, C.R. (1973) J. Biol. Chem. 248, 1813-1821) and has been used by a large number of investigators as an index of the activation of this enzyme in the intact cell. This communication reports that with the typical conditions used the dissociation of the protein kinase is not blocked throughout the extraction. This is demonstrated, with glucagon-stimulated rat liver as the example tissue, by the addition of exogenous protein kinase. These data call into question the meaning of results reported using this experimental approach. PMID- 6244291 TI - Structural and functional properties of cytochrome c oxidases isolated from sharks. PMID- 6244290 TI - Mechanisms of inactivation of molybdoenzymes by cyanide. AB - The reduced forms of xanthine oxidase, xanthine dehydrogenase, aldehyde oxidase, and sulfite oxidase are inactivated by cyanide. Following gel filtration to remove excess of reductant and cyanide, the isolated enzymes remain inactive. Thiocyanate, a product of inactivation of the oxidized forms of the xanthine- and aldehyde-oxidizing enzymes by cyanide, is not released during inactivation of the reduced enzymes. Studies with [14C]cyanide show that, while stoichiometric binding is required for the onset of inactivation, its continued binding is not essential to maintenance of the inactivated state. Electron paramagnetic resonance and absorption spectroscopic studies on the isolated inactivated enzymes show that prosthetic groups other than molybdenum are fully oxidized but that the molybdenum centers are modified. Reactivation is accomplished by incubation with suitable oxidants. Aerobic reactivation of inactive sulfite oxidase required only 1 eq of ferricyanide/active site. However, under rigorously anaerobic conditions, 3 to 4 mol of ferricyanide/active site were reduced, indicating that the molybdenum centers in the inactive enzyme had been reduced below the levels attained by the native enzyme during catalysis. PMID- 6244292 TI - Phosphorylation of rat hepatic fructose-1,6-bisphosphatase and pyruvate kinase. AB - Fructose-1,6-bisphosphatase from rat liver was phosphorylated with cyclic AMP dependent protein kinase and [gamma-32P]ATP. Brief exposure of the 32P-labeled enzyme to trypsin removed all radioactivity from the enzyme core and produced a single-labeled peptide. The partial sequence of the 17-amino acid peptide was found to be Ser-Arg-Pro-Ser(P)-Leu-Pro-Leu-Pro-(Ser2, Glx2, Pro2, Leu, Arg2). The kinetics of cyclic AMP-dependent protein kinase-catalyzed phosphorylation of native fructose bisphosphatase were compared with those of rat liver type L pyruvate kinase where the sequence around the phosphoserine is known (Arg-Arg-Ala Ser(P)-Val; Hjelmquist, G., Anderson, J., Edlund, B., and Engstrom, L. (1974) Biochem. Biophys. Res. Commun. 61, 559-563). The Km for pyruvate kinase (17 microM) was less than that for fructose bisphosphatase (58 microM); the Vmax was about 3-fold greater with pyruvate kinase as substrate. The relationship between the rates of phosphorylation of these native substrates and the amino acid sequences surrounding the phosphorylated sites is discussed. PMID- 6244293 TI - Electron paramagnetic resonance studies of the binding of copper to conalbumin. Probes of the structure and properties of the metal and anion binding sites. PMID- 6244295 TI - Effect of cyclic AMP on the intracellular degradation of newly synthesized collagen. AB - Prostaglandin E1 and cholera toxin increased the intracellular levels of cyclic AMP of human lung fibroblasts. With prostaglandin E1, the increase in cyclic AMP occurred within 10 min followed by a decline to less than one-half of peak values in 6 h. With cholera toxin, the increase occurred within 60 min but the level of cyclic AMP remained increased for 6 h. Both agents caused a decrease in collagen production as expressed as the proportion of newly synthesized protein represented by collagen. The increase in cyclic AMP levels was accompanied by a marked increase in the proportion of newly synthesized collagen which was degraded intracellularly prior to secretion. Analysis of the degraded collagen showed it to be predominantly less than 1000 daltons in molecular mass, but still in peptide linkage. The data are consistent with the hypothesis that cyclic AMP levels in diploid fibroblasts regulate the amount of collagen produced by fibroblasts, at least in part, by modulating the level of intracellular collagen degradation. PMID- 6244294 TI - Nucleotide sequence of the coding portion of human alpha globin messenger RNA. AB - The nucleotide sequence of the coding portion of human alpha globin mRNA has been determined by sequence analysis using human alpha globin cDNA cloned in bacterial plasmids. The sequence was obtained by a combination of direct sequence analysis of the cloned cDNA and analysis of cDNA obtained by primer extension, using short restriction endonuclease fragments of cloned alpha cDNA that were hybridized to human globin mRNA and elongated on the mRNA template by viral reverse transcriptase. The human alpha globin mRNA has an unexpectedly high G + C base composition (64.7%), similar to that observed for rabbit globin alpha mRNA, and displays a striking bias in the use of synonym codons for various amino acids. The bias in codon usage of human alpha globin mRNA is similar, with some exceptions, to that previously observed for rabbit alpha globin mRNA as well as for human and rabbit beta globin mRNAs. A detailed restriction endonuclease map of the human alpha globin cDNA is presented. PMID- 6244296 TI - Dissociation and reconstitution of membranes synthesizing the peptidoglycan of Escherichia coli. Lipid dependence of the synthetic enzymes. AB - The peptidoglycan synthetic enzymes can be dissociated with cholate and LiCl into components with mobilities on a gel filtration column in the same ranges as bovine serum albumin. The active enzymes can be separated further from the lipids necessary for synthesis by precipitation with ammonium sulfate. The needed lipids stable to hydrolysis with base. A protein needed for peptidoglycan polymerization can be separated from the other synthetic enzymes by hydroxylapatite chromatography. PMID- 6244297 TI - Hydrodynamic properties of the regulatory component of adenylate cyclase. AB - Hydrodynamic parameters of the regulatory component of adenylate cyclase, G/F, have been estimated by gel filtration and sucrose density gradient centrifugation. In solutions containing Lubrol 12A9, the protein has an apparent molecular weight of 130,000. G/F from various sources and resolved from the catalytic moiety of the enzyme by different techniques behaves similarly. Consistent with our previous proposal that this protein is the site of action of both guanine nucleotides and fluoride, treatment with these activating ligands causes a reduction in both the sedimentation coefficient and the Stokes radius of G/F. These changes suggest a loss of mass of approximately 40,000 daltons. Nevertheless, this alteration is fully reversible when ligands are removed, even if the liganded protein is first fractionated by gel filtration or sucrose density gradient centrifugation. PMID- 6244298 TI - The use of 6-labeled glucose to assess futile cycling in Escherichia coli. AB - To assess the "futile cycle" fructose-6-P leads to fructose-1,6-P2 leads to fructose-6-P in Escherichia coli we have grown the cells on [6-14C]glucose and determined label in the 1-position of glucose obtained from glycogen. In a variety of strains, including a wild type and a mutant without fructose diphosphatase, 1-position labeling was negligible. But there was little label in the 1-position of fructose-1,6-P2 either, which shows that hexose diphosphate and triose-P are not in equilibrium in this organism. Therefore, the lack of 1 position labeling in glycogen does not necessarily indicate lack of futile cycling. One strain, however, a temperature-sensitive glyceraldehyde-3-P dehydrogenase mutant grown at permissive temperature, gave substantial labeling of the 1-position of fructose-1,6-P2. In this strain 1-position labeling in glycogen was low, indicating minimal futile cycling. PMID- 6244299 TI - A temperature-sensitive single-stranded DNA-binding protein from Escherichia coli. AB - A temperature-sensitive single-stranded DNA-binding protein (SSB) has been purified from mutant Escherichia coli (ssb-1) cells by use of affinity chromatography on blue dextran-Sepharose. An altered amino acid sequence in the mutant protein is apparent in tryptic digests, confirming that the ssb mutation is in the structural gene. The mutant protein is less effective than the wild type in protecting single-stranded DNA from nuclease S1 digestion and in inhibiting DNA-dependent ATPases. The purified protein supports replication of phage G4 DNA in vitro at 30 degrees C, although higher levels of mutant protein, 4-fold higher than wild type, are needed to do so. The mutant protein becomes less active in supporting replication above 30 degrees C and becomes inactive at 42 degrees C within 1 min. Activity is restored upon return to 20 degrees C. Despite its temperature sensitivity in vivo and in vitro, the mutant binding protein can renature fully after exposure to 100 degrees C. Thus, the mutant protein is both heat-stable and functionally temperature-sensitive. PMID- 6244300 TI - Phosphorylation of acyl and dansyl derivatives of the peptide Leu-Arg-Arg-Ala-Ser Leu-Gly by the cAMP-dependent protein kinase. PMID- 6244301 TI - Protein kinase translocation following beta-adrenergic receptor activation in C6 glioma cells. AB - Incubation of C6 glioma cells with isoproterenol elicits an increase in cyclic AMP content, followed by an activation of cyclic AMP-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37). The cytoplasm of these glioma cells contains type II protein kinase and a small amount of cyclic AMP independent protein kinase. Following the persistent activation of cyclic AMP dependent protein kinase, catalytic subunits of this enzyme redistribute into particulate fractions. A maximal increase in nuclear protein kinase activity occurrs 45 to 60 min following isoproterenol. The addition of cyclic AMP or of Ca2+ with or without the specific ionophore A-23187 fails to increase the protein kinase activity of nuclei from control or isoproterenol-treated cells. Preincubation of the cells with vinblastine blocks the increase of nuclear protein kinase activity due to isoproterenol. If the incubation with vinblastine occurs simultaneously with isoproterenol, vinblastine fails to reduce the increase in nuclear protein kinase activity elicited by isoproterenol. PMID- 6244302 TI - Oxidation of tryptophan-21 alters the biological activity and receptor binding characteristics of mouse nerve growth factor. PMID- 6244303 TI - Studies on a mammalian hepatic binding protein specific for asialoglycoproteins. Evidence for receptor recycling in isolated rat hepatocytes. AB - Freshly isolated rat hepatocytes attained maximal ability to bind, internalize, and degrade 125I-asialo-orosomucoid after 5 h in suspension culture at 37 degrees C. Comparison of the number and distribution of the asialoglycoprotein binding sites of these cells revealed that 5% (6.7 x 10(4) receptors/cell) were on the external cell membrane with an average residency time of slightly less than 3 min. The remaining 95% were located intracellularly, as determined with detergent solubilized hepatocytes. Binding of ligand (asialo-orosomucoid) was time dependent, saturable, and dissociable. The dissociation constant for the single high affinity binding site was calculated to be 3.4 x 10(-8) M. The amount of asialo-orosomucoid metabolized by these cells over a period of 3 h at 37 degrees C was reduced 50% by the inclusion of 1 mM cycloheximide in the incubation medium. However, even in the absence of protein synthesis, 34 times more asialo orosomucoid was metabolized than could be bound by the cell surface receptors, or twice the total capacity of the intact hepatocyte. These results provide clear evidence for the stability of the binding receptor under conditions where the ligand is being continually destroyed and support the previously proposed recycling hypothesis (Tanabe, T., Pricer, W.E., Jr., and Ashwell, G. (1979) J. Biol. Chem. 254, 1038-1043). PMID- 6244304 TI - The chemical reactivity of fully maleylated cytochrome c. AB - The chemical reactivity of fully maleylated horse heart cytochrome c with oxidants, reductants, and iron ligands was studied in the presence and absence of MgCl2. In the absence of salt, the partly unfolded protein reacts rapidly with cyanide in the ferric state (k = 235 M-1s-1); the reaction is exothermic (delta H = -9.4 kcal/mol) and entropically unfavored (delta S = -7.0 e.u.). In 0.01 M MgCl2, the refoleded protein recovers the behavior towards cyanide of native cytochrome c. The oxidation-reduction potential of the refolded species is 190 mV. In the course of reduction of the unfolded form with dithionite, a reduced intermediate species (t 1/2 = 5.9 s) is observed; this species binds carbon monoxide rapidly, but the ligand dissociates thereafter. This shows that full maleylation does not disrupt the conformational stability of reduced cytochrome c. PMID- 6244305 TI - Cooperative calcium binding and ATPase activation in sarcoplasmic reticulum vesicles. PMID- 6244306 TI - Reversible alterations in the kinetics of cardiac sodium- and potassium-activated adenosine triphosphatase after partial removal of membrane lipids. PMID- 6244307 TI - Purification and characterization of a Saccharomyces cerevisiae exoribonuclease which yields 5'-mononucleotides by a 5' leads to 3' mode of hydrolysis. AB - An exoribonuclease producing 5'-mononucleotides has been purified from ribosomes of Saccharomyces cerevisiae. The enzyme has a broad pH optimum around 8.0, requires divalent cation, and is stimulated by monovalent cation with the cation and degree of stimulation being dependent on the substrate used. With either poly(A) or rRNA as substrate, the enzyme has a processive mode of hydrolysis. The oligonucleotides, (pA)3-5, are hydrolyzed by the enzyme, and the hydrolysis is dependent on a 5'-phosphate end group. Phosphorylation of the 3' end has little effect on the rate of hydrolysis. With [3H]poly(A) or [3H]rRNA, labeled differentially at the 5' termini, a more rapid release of 5'-terminal label can be shown, providing evidence that the enzyme hydrolyzes in a 5' leads to 3' direction. Further evidence for a 5' leads to 3' mode of hydrolysis is provided by a study of the products of the hydrolysis of [3H](pA)5 labeled at the 5' termini with 32P. No 32P label is found in (pA)2 which accumulates as an intermediate. PMID- 6244308 TI - Phosphorylation of rabbit skeletal muscle glycogen synthase by cyclic AMP dependent protein kinase and dephosphorylation of the synthase by phosphatases. PMID- 6244309 TI - Irreversible photoactivation of a pancreatic secretagogue receptor with cholecystokinin COOH-terminal octapeptides. AB - The photochemically reactive analog of cholecystokinin octapeptide (CCK-8), 2 nitro-5-azidobenzoyl-Gly-Asp-Tyr-(SO3H)-Met-Gly-Trp-Met-Asp-Phe-NH2 (NAB-Gly-CCK 8), has been used to stimulate irreversibly the receptor for CCK-8 on preparations of dispersed guinea pig pancreatic acini. When continuously present with acini in the dark, NAB-Gly-CCK-8 is a reversible stimulant of secretory protein discharge with an ED50 of 0.4 nM. After six cycles of photolysis of acini with NAB-Gly-CCK-8 followed by extensive washing and assay in peptide-free medium in the dark, the photoactivated label induces irreversible discharge. Irreversible discharge is proportional to the concentration of NAB-Gly-CCK-8 present during photolysis and is nearly equivalent in intrinsic activity to that induced by CCK-8 in the dark. Inclusion of a 5-fold excess of prephotolyzed NAB Gly-CCK-8 during photolysis partially protects against irreversible discharge, suggesting that the receptor irreversibly stimulated by NAB-Gly-CCK-8 is likely a receptor for peptides in the CCK family. Irreversible discharge requires metabolic energy supplied by oxidative phosphorylation and is dependent on extracellular Ca2+ and, thus, resembles that induced by reversible secretagogues. PMID- 6244310 TI - X-ray diffraction studies on crystalline complexes of the gene 5 DNA-unwinding protein with deoxyoligonucleotides. AB - Complexes of the gene 5 protein with a variety of oligodeoxynucleotides, ranging in length from two to eight and having several different sequences, have been formed and crystallized for x-ray diffraction analysis. The crystallographic parameters of four different unit cells, all of which are based on hexagonal packing arrangements, indicate that the fundamental unit of the complex is composed of 12 gene 5 monomers. PMID- 6244311 TI - Molecular structure of adeno-associated virus variant DNA. AB - When lysates of human cells, infected jointly with the defective parvovirus, adeno-associated virus (AAV), and a helper adenovirus, are banded to equilibrium in CsCl buoyant density gradients, virus particles of various densities are obtained. Infectious AAV particles mainly band at a density of 1.41 g/cm3 with a minor component at 1.45 g/cm3. Noninfectious AAV particles band at densities between 1.41 and 1.32 g/cm3. We have analyzed, by mapping with site-specific endodeoxyribonucleases, the molecular structure of the variant AAV DNA molecules obtained from these light density particles. The size of variant DNA molecules ranged from 100 to 3% of genome length. In general, the variant DNAs are deleted for internal regions but retain the genome termini. Some of the variant DNAs appear to be cross-linked, spontaneously renaturing molecules having structures analogous to replicating forms of AAV DNA. PMID- 6244312 TI - Hemoglobin switching in sheep. Cloning and characterization of the beta A and beta-like embryonic globin genes from genomic DNA. AB - Genomic DNA from a fetal sheep homozygous for the beta A gene was used to construct a library of one million cloned DNA fragments using the bacteriophage vector, Charon 4A. Screening of 150,000 plaques from this library using radioactive beta-globin gene sequences resulted in the isolation of two recombinant bacteriophage containing globin genes. One of these, S beta AG-21, contains the complete adult beta A-globin gene as demonstrated by hybridization and restriction endonuclease analysis. In common with adult globin genes from other species, the beta A gene contains small (105 base pairs) and large (900 base pairs) intervening sequences. The second recombinant bacteriophage, SG-4, contains a complete embryonic beta-like globin gene which is expressed in the sheep embryo as demonstrated by hybridization analysis with cDNA made from sheep embryonic globin mRNA. Although differing in its restriction endonuclease map from the adult beta-globin genes, SG-4 appears to contain a large intervening sequence of at least 750 base pairs in length. Finally, preliminary evidence is discussed which indicates that a Pvu II site just 5' to the Cap site may be a common feature of sheep globin genes. PMID- 6244313 TI - Isolation and characterization of a 15-kilobase genomic sequence coding for part of the Pro alpha 2 chain of sheep type I collagen. AB - DNA fragments, prepared by partial Eco RI digestion of fetal sheep liver genomic DNA, were used to prepare a "library" of amplified genomic sequences with the lambda vector Charon 4A. Several recombinant plaques were identified by their ability to hybridize to 32P-labeled cDNA prepared from fetal sheep tendon type I procollagen mRNA. Two of these recombinant DNA bacteriophages (SpC3 and SpC7) were identified as containing procollagen pro alpha 2 gene sequences by their ability to specifically anneal to procollagen pro alpha 2 mRNA. Restriction endonuclease and hybridization to a cloned pro alpha 2 cDNA demonstrated that approximately half (2.5 kilobases) of the pro alpha 2 mRNA sequence is distributed over 15 kilobases of genomic DNA. Restriction maps of SpC3 and SpC7 demonstrated that these two DNA fragments contain overlapping sequences of the pro alpha 2 gene. Electron microscopy and R-loop analysis of SpC3 revealed that at least 12 to 16 intervening sequences are distributed throughout the length of this gene fragment. PMID- 6244314 TI - Compositional dependence of the formation of calcium phosphate films on bioglass. AB - Bioglass, which has a composition of sodium carbonate, calcium carbonate, phosphorous pentoxide and silica, has been shown to bond to living bone. This ability is dependent on controlled surface reactions. Investigators with 45S5 bioglass have demonstrated that the formation of a SiO2-rich layer and a calcium phosphate film on its surface in an aqueous environment is associated with the film bonding the bioglass to bone. The objects of this research were: 1. To study SiO2 dependence on the formation of a silica-rich layer and calcium phosphate films on a bioglass surface in a simulated physiological solution, and 2. To establish a correlation between in vitro surface reactions and in vivo bonding ability. It was discovered that three types of reactions occur in a simulated physiological solution depending on bioglass composition: 1. A calcium phosphate film and SiO2-rich layer form simultaneously and the reaction rate is fast for bioglasses which have a lower content of SiO2 (approximately 46 mol% SiO2). 2. A SiO2-rich layer forms first and a calcium phosphate film develops later between the aqueous environment and the SiO2-rich layer for bioglasses whose SiO2 content is between 46--55 mol %. 3. A calcium phosphate film does not form for glasses whose SiO2 content is more than 60 mol %. PMID- 6244315 TI - Malignant fibrous histiocytoma of bone in a renal-transplant patient. Case report. PMID- 6244316 TI - Synthesis of type III collagen by fibroblasts from the embryonic chick cornea. AB - Synthesis of collagen types I, II, III, and IV in cells from the embryonic chick cornea was studied using specific antibodies and immunofluorescence. Synthesis of radioactively labeled collagen types I and III was followed by fluorographic detection of cyanogen bromide peptides on polyacrylamide slab gels and by carboxymethylcellulose chromatography followed by disc gel electrophoresis. Type III collagen had been detected previously by indirect immunofluorescence in the corneal epithelial cells at Hamburger-Hamilton stages 20--30 but not in the stroma at any age. Intact corneas from embryos older than stage 30 contain and synthesize type I collagen but no detectable type III collagen. However, whole stromata subjected to collagenase treatment and scraping (to remove epithelium and endothelium) and stromal fibroblasts from such corneas inoculated in vitro begin synthesis of type III collagen within a few hours while continuing to synthesize type I collagen. As demonstrated by double-antibody staining, most corneal fibroblasts contain collagen types I and III simultaneously. Collagen type III was identified biochemically in cell layers and media after chromatography on carboxymethylcellulose be detection of disulfide-linked alpha l (III)3 by SDS gel electrophoresis. The conditions under which the corneal fibroblasts gain the ability to synthesize type III collagen are the same as those under which they lose the ability to synthesize the specific proteoglycan of the cornea: the presence of corneal-type keratan sulfate. PMID- 6244317 TI - Organization of ribosomal genes in Paramecium tetraurelia. AB - The macronuclear ribosomal DNA (rDNA) of the ciliated protozoan Paramecium tetraurelia (stock 51) was analyzed by digestion with restriction endonucleases. The fragments which contained ribosomal RNA (rRNA) coding sequences and spacer sequences were identified. The spacer sequences exhibited some heterogeneity in size. The genes coding for 5.8S RNA, but not for 5S RNA, are linked to the 17S and 25S rRNA genes. Complementary RNA, synthesized from rDNA of stock 51, was hybridized with restriction digests of whole cell DNA from six other allopatric stocks of this species. The restriction patterns of the rDNA from these seven stocks were, in general, very similar, and the sizes of the coding sequences were identical in all seven stocks. Only the restriction pattern of rDNA from stock 127 differed significantly from that of stock 51. The rDNA from stock 127 was isolated and characterized, and with the exception of the restriction pattern of its spacer, it resembled the rDNA from stock 51. It is concluded that the rDNA repeat in Paramecium, including the spacer, has, in general, been conserved during the course of evolution. It is suggested that in some species, even in the absence of genetic exchange among geographically separated populations, selection pressure may act to conserve spacers of tandemly repeated rDNA. The conservation may be related to the number of rDNA copies in the germinal nucleus. PMID- 6244319 TI - Studies of enzyme-mediated reactions. Part 13. Stereochemical course of the formation of histamine by decarboxylation of (2S)-histidine with enzymes from Clostridium welchii and Lactobacillus 30a. PMID- 6244318 TI - Studies of Schwann cell proliferation. I. An analysis in tissue culture of proliferation during development, Wallerian degeneration, and direct injury. AB - In this paper the stimuli for and pattern of Schwann cell proliferation are defined under various experimental conditions. We used a tissue culture system in which fetal rat dorsal root ganglia, treated to eliminate contaminating fibroblasts (Wood, P., 1976, Brain Res. 115:361--375), appear to recapitulate many aspects of the developing peripheral nervous system. We observed that: (a) proliferation of Schwann cells on neurites is initially rapid, but, as each neurite becomes fully ensheathed, division slows considerably and is confined to the periphery of the outgrowth; (b) during the period of rapid proliferation, excision of the ganglion causes a rapid decay in the number of dividing cells; (c) excision of the ganglion from more established cultures in which there was little ongoing proliferation resulted in a small increase in labeling at the site of excision for all Schwann cells and a substantial increase in labeling for myelin-related cells with a peak labeling period at 4 d; (d) direct mechanical injury during Wallerian degeneration is mitogenic for Schwann cells; (e) a variety of potential mitogens failed to stimulate Schwann cell proliferation, and (f) replated cells have a slightly higher level of proliferation and show a small and variable response to the addition of cAMP. PMID- 6244320 TI - Adrenocorticotropin, beta-lipotropin, beta-endorphin, and corticotropin-releasing factor-like activity in an adrenocorticotropin-producing nephroblastoma. PMID- 6244321 TI - Effects of oral thyrotropin-releasing hormone, exogenous thyroid-stimulating hormone, and withdrawal of triiodothyronine on 131I uptake after subtotal thyroidectomy. PMID- 6244322 TI - Lack of modulation of pituitary hormone stress response by neural pathways involving opiate receptors. AB - To evaluate the role of the opiate-like peptidergic pathways in modulating the pituitary hormone response to stress, we measured the GH, PRL, and cortisol responses to hypoglycemia and exercise in normal subjects with and without pretreatment with naloxone, given in the centrally active dose of 0.4 mg iv. Basal serum levels of GH, PRL, and cortisol were not changed significantly by prior naloxone administration. The maximum incremental response of GH to exercise was significantly blunted (13.1 +/- 1.6 vs. 6.0 +/- 1.4; P less than 0.001) by prior naloxone administration. Pretreatment with naloxone did not affect the responses of GH, PRL, or cortisol to hypoglycemia or the PRL response to L-dopa. On the basis of these studies we conclude that the opiate-like peptidergic pathways are not important in the regulation of basal levels of GH, PRL, and cortisol and have only a modest modulating influence on the stress-induced release of the hormones, which may be obscured in the face of severe stress. PMID- 6244323 TI - Increased 17 beta-hydroxysteroid dehydrogenase activity in a masculinizing adrenal adenoma in a patient with isolated testosterone overproduction. AB - The patient studied had noted the onset of virilization shortly after menopause. Urinary 17-ketosteroid levels were normal, as were fractionated 17-ketosteroid levels by gas liquid chromatography, but for 3 yr, serum testosterone levels had been greater than 490 ng/dl. The ovaries were found to be normal by laparoscopy. Abdominal exploration revealed a 1-cm adenoma in the right adrenal. A part of the adenoma excised from our patient was homogenized and incubated with 5 microCi [14C]androstenedione. Five percent of the 14C was converted by the tumor homogenate to a metabolite with the same mobility as testosterone on LH-20 chromatography. After thin layer chromatography, the radiolabeled material together with 3H-labeled authentic testosterone were crystallized to a constant specific activity. The net rate of testosterone synthesis by the tumor was 26 pmol/mg wet tissue wt.h vs. 0.56 pmol/mg.h by a control adrenal homogenate. Thus, the tumor demonstrated a 50-fold increase in 17 beta-hydroxysteroid dehydrogenase activity compared to normal adrenal tissue. This is the first report to identify altered activity of a specific enzyme system in this syndrome of isolated adrenal testosterone overproduction. PMID- 6244324 TI - Adenosine 3',5'-monophosphate response to parathyroid hormone: familial hypocalciuric hypercalcemia versus typical primary hyperparathyroidism. AB - We investigated cAMP metabolism during and after a 15-min infusion of parathyroid hormone (PTH) in 7 normals, 13 patients with typical primary hyperparathyroidism (1HPT), and 6 patients with familial hypocalciuric hypercalcemia (FHH). Nephrogenous urinary cAMP excretion rate reached a peak during the first or second 30 min urine collection interval after the start of the PTH infusion in all subjects. cAMP concentration in plasma reached a peak within 5--20 min of the start of the infusion and then decreased with an initial half-time of 15 min. The peak value of nephrogenous urinary cAMP excretion rate was lower in the group with 1HPT than in the group with FHH or in normals (119 vs, 275 vs. 204 nmol/100 ml glomerular filtrate; P less than 0.0 5 for both comparisons). Similarly, the peak value of plasma cAMP concentration was less in 1HPT subjects than in FHH patients or in normals (11.1 vs. 17.1 vs. 16.6 nmol/100 ml, respectively; P less than 0.05 for both comparisons). For purposes of diagnostic classification, the two hypercalcemia groups could be more completely separated by the values of either the renal calcium to creatinine clearance ratio or the plasma PTH concentration than by the values of inidices of cAMP response to PTH. The differences in cAMP response to PTH between FHH and 1HPT patients could be secondary to differences in circulating PTH concentrations (these are lower in subjects with FHH) or could reflect a renal lesion more closely related to the underlying etiology of FHH. PMID- 6244325 TI - Dissociation and association between calcitonin and adrenocorticotropin secretion. PMID- 6244326 TI - Studies of the C-21 and C-19 steroids and HLA genotyping in siblings and parents of patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. PMID- 6244327 TI - Transsphenoidal microsurgery in the treatment of acromegaly and gigantism. AB - Twenty-five patients with acromegaly and 3 patients with gigantism underwent transsphenoidal microsurgery in an attempt to remove the tumor and preserve normal pituitary function whenever possible. An adenoma was identified and removed in 27 of 28 patients. Evaluation 3--6 months postoperatively revealed a GH level less than 5 ng/ml in 29 patients, 5--10 ng/ml in 4 patients and 11--29 ng/ml in 4 other patients. Dynamics of GH secretion were normal in 11 patients who had normal pituitary function and are considered cured. Two patients with low or undetectable GH levels are also considered cured at the expense of being hypopituitary. Three of 7 patients with normal basal GH levels but abnormal dynamics of GH secretion relapsed within 1 yr. Eleven of the 13 patients considered cured did not have extrasellar extension, while 14 of the 15 patients not cured had extrasellar extension. Five patients who were not cured with surgery received radiation therapy. Three patients were treated with an ergot derivative, Lergotrile mesylate, after surgery and radiation therapy failed to normalize GH levels. Transsphenoidal microsurgery is an optimal form of therapy for patients with acromegaly or gigantism, especially those with no extrasellar extension. Dynamics of GH secretion are very useful in evaluating the completeness of adenoma removal. PMID- 6244328 TI - Hormonal studies in obligate heterozygotes and siblings of patients with 11 beta hydroxylase deficiency congenital adrenal hyperplasia. AB - Hormonal response to ACTH stimulation and HLA genotyping were determined in families of patients with 11 beta-hydroxylase deficiency congenital adrenal hyperplasia. Neither hormonal measurements nor HLA genotyping were useful for the detection of heterozygosity in the families. PMID- 6244329 TI - Enzyme immunoassay for measurement of antibodies to herpes simplex virus infection: comparison with complement fixation, immunofluorescent-antibody, and neutralization techniques. AB - An enzyme immunoassay (EIA) was developed for detecting antibody to herpes simplex virus, and the results were compared with those of complement fixation, indirect immunofluorescent-antibody, and plaque reduction neutralization tests. Test sera showed very little nonspecific reactivity even at a starting dilution as low as 1:10. EIA results showed excellent correlation with results obtained by the neutralization test, with an average gain in sensitivity of 1.65. EIA proved very useful in detecting current herpes simplex virus infection, and antibody appeared in all cases soon after clinical onset. EIA appears to be a rapid, sensitive, and specific method for routine demonstration of herpes simplex virus antibody in a clinical setting. PMID- 6244331 TI - Specific identification of human cytomegalovirus isolates by anti-complement immunofluorescence with immune hamster sera. AB - An anti-complement immunofluorescence test utilizing cytomegalovirus immune hamster sera specifically identified cytomegalovirus isolates showing an early, typical cytopathic effect. Inclusion of a control conjugate against adenovirus group antigen permitted correct identification, as adenoviruses, of a few isolates initially suspected of being cytomegalovirus on the basis of cytopathic effect. PMID- 6244330 TI - Rapid detection and identification of JC virus and BK virus in human urine by using immunofluorescence microscopy. AB - An indirect immunofluorescence method was developed and used to detect urinary excretion of abnormal transitional cells infected with JC virus (JCV) or BK virus (BKV). This method was compared with urinary cytology, electron microscopy, viral culture, and viral serology in groups of immunosuppressed renal transplant recipients and normal controls. The indirect immunofluorescence method detected and identified JCV excretion in four persons, BKV excretion in one person, and both JCV and BKV excretion in eight others. Viral antigen was identified only in the nuclei of cytologically abnormal cells. Of these 13 persons, 8 also had polyoma virions detected in the urine by electron microscopy. With repeated study of sequential urine samples, 30% of transplant recipients and 6% of normal controls were positive by one or more microscopy methods. Serological results confirmed a high incidence of both JCV and BKV multiplication in the immunosuppressed patients. However, serology did not correlate directly with urinary virological findings. Urinary cytology and the indirect immunofluorescence method were rapid and sensitive methods for detecting and identifying urinary excretion of JCV and BKV. PMID- 6244332 TI - Antigenic comparisons of two new rotaviruses from rhesus monkeys. AB - Two rotavirus strains isolated in cell culture from infant rhesus monkeys with diarrhea were closely related to SA 11 virus and to each other by plaque reduction neutralization tests. However, results of immune electron microscopy suggested possible antigenic differences between the two rhesus rotavirus strains. PMID- 6244333 TI - Adverse effects of cytomegalovirus vaccination in mice. AB - Studies of live attenuated cytomegalovirus (CMV) vaccine have recently been initiated in man. The possibilities of latent infection and disease resulting from reactivation of vaccine virus are major concerns. Because markers for attenuation of tissue culture-passaged mouse CMV (MCMV) exist, studies of potential adverse effects of vaccination were initiated in mice. Plaque-purified MCMV was passed 12 times in cell culture ("vaccine virus") and shown to be attenuated by virtue of loss of lethality and diminished replication in reticuloendothelial organs of normal mice. Although subcutaneous inoculation of 10(5) plaque-forming units of wild virus was lethal for mice immunosuppressed with antilymphocyte serum (18/18 died), "vaccine MCMV" killed only 3/18 (P < 0.05) and was thus shown to be highly attenuated even in immunosuppressed animals. 4 mo after subcutaneous inoculation of vaccine MCMV, no infectious virus was detectable in the tissues of normal C(3)H mice. However, immunosuppression with anti-lymphocyte serum and cortisone caused MCMV reactivation, dissemination, and wide-spread cytomegalic inclusion disease in 19 of 20 animals. Characterization of the reactivating virus recovered from salivary glands indicated that reversion to virulence had occurred. Thus, vaccine MCMV, although markedly attenuated initially, established latent infection, reactivated after immunosuppression, and reverted to virulence, at least in salivary gland tissue. These data from the murine model substantiate the need for careful surveillance and virologic study of patients given experimental CMV vaccine. PMID- 6244334 TI - Effects of melanotropic peptides on fetal adrenal gland. AB - Adrenal glands from early, mid, and late fetuses of rabbit, guinea pig, and rat, and from newborn animals of each species, were incubated for 1-4 h with and without 0.1 nM-1 microM ACTH, alpha- or beta-melanocyte-stimulating hormone (alpha MSH or beta MSH). The effects of the peptides were measured on production of glucocorticoids, and on incorporation of labeled thymidine or leucine into DNA or protein, respectively. The findings were similar in all three species. ACTH stimulated synthesis of glucocorticoids throughout fetal life. Potency increased progressively, as reflected by declining minimal effective dose and rising maximal response. In early and mid fetus alpha MSH and beta MSH caused a modest glucocorticoid steroidogenic effect. ACTH and alpha MSH stimulated DNA and protein synthesis in the early and mid fetal gland. alpha MSH was more potent than ACTH in these respects, minimal effective dose being generally 10 times less and maximal response 25-200% greater. The effects diminished or disappeared in the late fetal and newborn gland. These data indicate that alpha- and beta MSH possess steroidogenic or growth-promoting properties, or both, for the fetal adrenal gland. PMID- 6244335 TI - Reversal of ethinyl estradiol-induced bile secretory failure with Triton WR-1339. AB - The effects of Triton WR-1339 and phenobarbital on ethinyl estradiol bile secretory failure were examined to determine the mechanism responsible for decreased bile salt excretion. When administered to ethinyl estradiol-treated rats, Triton WR-1339 restored bile salt independent bile flow and maximum taurocholate transport, whereas phenobarbital corrected bile flow only. Ethinyl estradiol decreased the activities of Na(+)-K(+)-ATPase, 5'-nucleotidase, while increasing the activities of Mg(++)-ATPase and alkaline phosphatase. In contrast to these heterogeneous changes in surface membrane enzyme activities, the number and affinity of [(14)C]cholic acid carriers were not altered. When administered in vivo or added directly to surface membrane fractions Triton WR-1339 restored the activities of Na(+)-K(+)-ATPase and Mg(++)-ATPase of rats treated with ethinyl estradiol through a process that did not require protein synthesis (unaffected by cycloheximide). Phenobarbital also restored the activity of Na(+) K(+)-ATPase to control levels, but, unlike Triton WR-1339 it did not correct the defect responsible for reduced bile salt secretion. Ethinyl estradiol increased the concentration of cholesterol esters in surface membrane fractions. When administered to ethinyl estradiol-treated rats, Triton WR-1339 restored cholesterol ester concentrations to normal, whereas phenobarbital did not. These combined data suggest that decreased or altered bile salt carriers or reduced sodium driving forces resulting from impaired activity of Na(+)-K(+)-ATPase are not responsible for decreased bile salt excretion in ethinyl estradiol-treated rats. It is proposed that the diverse changes in surface membrane function, which are associated with ethinyl estradiol bile secretory failure, may be the result of a generalized alteration in membrane lipid structure. PMID- 6244336 TI - Cellular and humoral immunity in the pathogenesis of recurrent herpes viral infections in patients with lymphoma. AB - 86 patients with lymphoma were evaluated prospectively for clinical and laboratory evidence of recurrent varicella-zoster, herpes simplex, and cytomegalovirus infections during the first 16 mo of treatment. Cellular immunity to the viral antigens was measured by in vitro lymphocyte transformation and interferon production. Antibody titers and nonspecific measures of cellular immunity, including T-cell quantitation and transformation to phytohemagglutinin, were also assessed. The patients treated with radiation and chemotherapy had the highest incidence of reactivation of each of the viruses (15-19%). Greater susceptibility to herpes viral reactivation in these patients correlated with suppression of cell-mediated immunity to the specific virus. In individual patients, suppression of cellular immunity to the specific herpes viral antigen preceded each episode of reactivation, but recurrent infection did not occur in all patients with diminished specific lymphocyte transformation. Absence of the response appears to be a necessary but not a sufficient condition for the recrudescence of latent infection. Better preservation of cellular immunity to herpes simplex antigen during treatment was associated with infrequent reactivation of herpes simplex. In 25 patients with acute herpes zoster, uncomplicated recovery from the infection was accompanied by the development of lymphocyte transformation and interferon production to varicella-zoster antigen. Quantitation of T-cell numbers and phytohemagglutinin transformation did not correlate with the presence of viral cellular immunity in treated patients. Responses returned while T-cell numbers were low, and the recovery of phytohemagglutinin transformation often preceded recovery of the responses to viral antigens. Although some patients had deficiencies in viral cellular immunity at diagnosis, the duration of the suppression of specific antiviral responses resulting from treatment appears to be the most important factor predisposing to the recurrence of herpes infections in lymphoma patients. PMID- 6244337 TI - Adult pulmonary cytomegalic inclusion disease: report of a case. AB - A case is presented of pulmonary cytomegalic inclusion disease in adult. The condition was only diagnosed post mortem. A detailed description of the inclusions and inclusion-bearing cells is given. Histochemical observations which reveal an outer and inner zone to the intranuclear inclusion body are confirmed. Electron microscopy shows the viral basis of the infection. The morphology of the virus particles is compatible with a herpesvirus infection. PMID- 6244338 TI - [Prostaglandins, steroids and reception (an experiment in modelling the structure of the active adrenoreception centers)]. PMID- 6244339 TI - Use of volunteer parent simulators to help medical students learn interview skills. PMID- 6244340 TI - Cimetidine--a review. PMID- 6244341 TI - Changes in the activities of some digestive enzymes of Channa punctatus, exposed chronically to mercuric chloride. AB - The effect of a chronic exposure to sublethal concentration of mercuric chloride (0.3 mg/l) on the activities of some enzymes in the digestive system of the teleost fish Channa punctatus was examined after 15 and 30 days of treatment. Glucose-6-phosphatase was significantly inhibited in the intestine and pyloric caeca. No marked alterations were observed in the activities of maltase and lactase except for elevation in maltase activity and inhibition in lactase activity in the intestine and pyloric caeca after 15 days of treatment. Three peptidases (aminotripeptidase, glycylglycine dipeptidase and glycyl-1-leucine dipeptidase) showed decreased activities in all parts of the digestive system. A decrease was also observed in the activity of lipase except for the stomach where inhibition after 15 days was insignificant. The results indicate that the activities of all the enzymes examined are inhibited in intestine and pyloric caeca and digestion of proteins and lipids may be more affected by mercury than the digestion of some carbohydrates. PMID- 6244342 TI - Aspects of heat inactivation of foot-and-mouth disease virus in milk from intramammarily infected susceptible cows. AB - In skim milk obtained from susceptible cows after intramammary and intravenous inoculation (primary infected milk), foot-and-mouth disease (FMD) virus type O1 was slower inactivated by heat treatment than virus that had been added to pre exposure skim milk. Residual virus infectivity in heated primary infected milk was more efficiently detected in bovine thyroid cell cultures than in secondary pig kidney (PK2) cell cultures. Untreated primary infected milk was found to inhibit both FMD-virus and vesicular stomatitis virus plaque formation in PK2 cells, suggesting the presence of interferon. The results of further tests confirmed that the interfering activity in unheated primary infected milk was indeed caused by an interferon. Interferon excretion in primary infected milk was investigated using a series of milk samples from three cows. Maximum interferon titres were found after 24 h, coinciding with or shortly after the first virus excretion peak. The results are discussed with particular reference to the use of primary infected milk in studies of the thermal inactivation of FMD-virus. PMID- 6244343 TI - Commercial milk products and indigenous weaning foods in a rural West African Environment: a bacteriological perspective. AB - Two commercially available baby milks, one 'biologically acidified', the other 'non-acidified', and a traditional weaning food, millet gruel, were prepared and stored under village conditions in West Africa. Increases in total colony count and in number of Bacillus cereus, Clostridium welchii, Staphylococcus aureus and Escherichia coli were determined in these products when stored as commonly practised at ambient temperatures over a period of 8 h. Poor hygiene during preparation was indicated by readily detectable numbers of coliforms and E. coli in freshly prepared samples of each of the milks, though the cooked local gruel seemed less vulnerable in this respect. The rate of increase in the numbers of these organisms was lower in the acidified milk when prepared with unboiled water containing high numbers of coliforms and E. coli. Increases in total colony count and in numbers of Staph. aureus were also less marked in the acidified milk. When food was not eaten soon after preparation the problem of bacterial overgrowth was as great with the local gruel as with the considerably more nutritious reconstituted milks. PMID- 6244344 TI - Evidence of infection by viruses in small British field rodents. AB - Four populations of small wild British rodents were studied by capture--re capture methods over a period of three years. Samples of blood were taken from these animals and tested for antibodies to nine viruses. Animals were removed from another 11 sites around the UK, and immunosuppressed. Samples of tissue from these animals were tested for the presence of viruses by passage in laboratory mice and serum samples from some of them were tested for antibody to the nine viruses. Indications were found of the possible influence of epizootic outbreaks of certain diseases on animal populations. PMID- 6244345 TI - Cyclic AMP modulation of Fc receptor expression on a pre-B cell lymphoma. AB - Cyclic AMP-elevating agents have been shown to increase the expression of Fc receptors on the Abelson virus-induced pre-B cell tumor ABE-8. Such agents included isoproterenol, PGE1, 3-isobutyl-1-methyl xanthine, and 8 BrcAMP. The positive inductive effect produced by these agents was inhibited by 8 BrcGMP and PGF2 alpha, which putatively elevate cyclic GMP levels. Other agents also shown to induce Fc receptor expression were LPS and certain batches of fetal calf sera. In contrast to the inductive effect produced by cyclic AMP elevating agents, 8 BrcGMP and PGF2 alpha were unable to reverse the increased Fc receptor expression produced by LPS and fetal calf sera. Thus, these latter agents may act via a qualitatively different mechanism in producing a change in phenotypic expression. The results of this study are discussed in terms of the use of tumor cells as a model system for studying the pharmacologic control of lymphocyte differentiation. PMID- 6244346 TI - Immunosuppression by 334C murine leukemia virus: viral specificity and the activation of immunosuppressive effects during cloned viral leukemogenesis. PMID- 6244347 TI - In vitro induction of cytotoxic T lymphocytes specific for Epstein-Barr virus transformed cells: kinetics of autologous restimulation. PMID- 6244348 TI - H-2 antigen requirements in the in vitro induction of SV40-specific cytotoxic T lymphocytes. AB - T cytotoxic cells generated to syngeneic SV40 virus transformants lyse only SV40 target cells that are syngeneic at the H-2 locus. In contrast, SV40-specific tumor transplantation immunity shows no requirements for syngeneic H-2. Inoculation of allogeneic or even xenogeneic transformants will confer immunity to a challenge of syngeneic SV40 tumor cells. The experiments described here represent an attempt to reconcile these apparently conflicting observations. In our hands, generation of SV40-specific T cytotoxic cells in vitro requires both in vivo priming and secondary in vitro sensitization. We have found that priming for a secondary syngeneic-restricted response requires only that the cell employed be SV40 transformed. That is, priming may be accomplished with syngeneic, allogeneic, or xenogeneic SV40 transformants. Thus, the apparent lack of H-2 restriction in vivo immunity does not eliminate a role for the H-2 restricted cytotoxic T cell in tumor transplantation immunity. PMID- 6244349 TI - Nonspecific inhibition of encephalomyocarditis virus replication by a type II interferon released from unstimulated cells of Mycobacterium tuberculosis sensitized mice. AB - Unstimulated peritoneal cells (PC) from mice sensitized with nonviable Mycobacterium tuberculosis in an oil-droplet emulsion inhibit encephalomyocarditis virus (EMCV) replication in mouse embryo fibroblast monolayers. Concentrations of mycobacteria ranging from 50 to 500 microgram elicit PC that inhibit EMCV replication greater than 99%. PC collected 2 to 6 weeks post-inoculation of mycobacteria are most effective (greater than 99% inhibition), although cells harvested from mice 7 through 10 weeks inhibit viral replication greater than 90%. Inhibition of replication is not detected unless PC are in contact with infected monolayers for a minimum of 8 to 10 hr; nonviable PC are not effective. Optimal inhibition occurs in cultures infected with a low multiplicity of EMCV that are incubated at 37 degrees C. Inhibition of replication is not due to pH changes or depletion of nutrients in cultures, adsorption and/or inactivation of EMCV by macrophages, or killing of monolayers by the PC. Inhibition of viral replication by the unstimulated PC appears to be due to an interferon that is similar but not identical to classical mouse Type II interferon. PMID- 6244351 TI - The effect of particle size on the immunodepressive properties of silica. PMID- 6244350 TI - Use of the periodate oxidation coupling method for the detection of antibody and antibody-producing cells specific for staphylococcal lipoteichoic acid. AB - The periodate oxidation and chromium chloride coupling methods were compared for their ability to sensitize indicator erythrocytes with staphylococcal lipoteichoic acid (LTA) for the detection of specific antibody. Erythrocytes, sensitized with periodiate-activated lipoteichoic acid, were found to be superior for use in both passive immune hemagglutination and hemolysis tests as well as in the technique of localized hemolysis-in-gel for the detection of specific antibody-producing cells against LTA. PMID- 6244352 TI - A type-specific antiserum induced bya major herpesvirus type 1 glycoprotein. AB - A type-specific antiserum was prepared against VP 7/8, the major HSV-1 type specific glycoprotein. The specificity of this antiserum was demonstrated by both neutralization of HSV-1 infectivity and immunoprecipitation followed by SDS polyacrylamide gel electrophoresis of the immunoprecipitates. Only minimal cross reactivity with HSV-2 was observed. This major VP 7/8 glycorprotein was also purified from a host of virus-induced proteins with the specific immunoadsorbent prepared with anti-VP 7/8 serum. The one-step purification of this type-specific neutralizing antigen of HSV-1 should allow the development of a sensitive and specific radioimmunoassay. PMID- 6244353 TI - Separation of human blood monocytes and lymphocytes on a continuous Percoll gradient. AB - A method for separation of human blood monocytes and lymphocytes is described. Mononuclear leukocytes are centrifuged on a continuous gradient of colloidal silica particles (Percoll) in phosphate-buffered saline. This leads to formation of 4 bands: a layer containing dead material (if present) which did not enter the gradient; a layer near the bottom of the tube containing granulocytes and red cells, and two other bands in between. The upper one is enriched for monocytes (av. 78%) and the lower one for lymphocytes (av. 98%). The final yields of these cell types are 73% and 79%, respectively, and their viability is greater than 95%. No functional impairments could be detected by different criteria including the ability of B lymphocytes to produce immunoglobulins when stimulated with pokeweed mitogen and the ability of monocytes to phagocytize opsonized red cells and latex particles. PMID- 6244354 TI - A new method for measurement of human thyroid-stimulating immunoglobulins. PMID- 6244355 TI - Otolaryngological quiz. PMID- 6244356 TI - Activation induced by luteinizing hormone of type II protein kinase dependent on cyclic adenosine monophosphate and phosphorylation of soluble proteins in porcine granulosa cells. AB - The present experiments were designed to study whether exogenous LH could elicit acute cyclic AMP-mediated activation of cyclic AMP-dependent protein kinase and phosphorylation of cellular protein in intact porcine granulosa cells. Incubation of porcine granulosa cells (from 3 to 5 mm diameter follicles) with 2 microgram luteinizing hormone/ml (LH) caused a significant rise of cellular cyclic AMP content within 2 min of the addition of LH. The increase was dose-dependent and occurred between doses of 0.2 and 2.0 microgram LH/ml. Luteinizing hormone also caused a time- and dose-dependent dissociation of the type II cyclic AMP dependent protein kinase isozyme in porcine granulosa cells. Luteinizing hormone (0.05--2 microgram/ml) significantly dissociated the cyclic AMP-dependent protein kinase between 2 and 30 min after stimulation. The protein kinase dissociation was a specific effect of LH and was not elicited by either adrenocorticotrophic hormone or prolactin. During the period of LH-induced protein kinase activation, several soluble granulosa cell proteins, ranging in molecular weights from about 43 000 to 99 000, became phosphorylated in a time-dpeendent and hormone-specific manner. The results suggest that cyclic AMP-mediated activation of granulosa cell type II cyclic AMP-dependent protein kinase may be a prerequisite in the short term molecular action of LH leading to LH-specific phosphorylation of several soluble granulosa cell proteins of an as yet unidentified function. PMID- 6244357 TI - Lymphomagenicity of recombinant mink cell focus-inducing murine leukemia viruses. AB - Recombinant mink cell focus-inducing (MCF) murine leukemic viruses, as well as ecotropic and xenotropic viruses, were tested for ability to accelerate or cause development of lymphoma in AKR and other strains of mice. Of the three classes of virus isolated from AKR, only the MCF viruses were able to accelerate development of AKR lymphoma. This fully supports the idea that the MCF viruses are the proximal cause of spontaneous AKR lymphoma. MCF lymphomagenicity was strain specific, however, in that AKR MCF viruses did not induce lymphomas in many murine strains; they were moderately lymphomagenic in C3H/Bi mice and in National Institutes of Health Swiss partially congenic for Akv-1 or Akv-2. In contrast, MCF viruses from nonthymic hematopoietic neoplasms of C3H/Fg, BALB/c, or mice partially congenic for ecotropic virus loci (Akv-1, Akv-2, Fgv-1, C58v-1, and C58v-2) were not able to accelerate or cause lymphomia in AKR or any other mouse strain tested, including some of the strains of origin. MCF lymphomagenicity correlated with thymic origin in the virus and with ability to replicate in the thymus. PMID- 6244358 TI - Increased sensitivity of human lymphoid lines to natural killer cells after induction of the Epstein-Barr viral cycle by superinfection or sodium butyrate. AB - Superinfection of latently Epstein-Barr virus (EBV)-carrying Raji cells with the P3HR-1 substrain EBV, known to induce the entry of a substantial fraction of cells into an abortively lytic cycle, increased the susceptibility of the cells to natural killer (NK) effect of human blood lymphocytes. Reciprocal cold-target competition tests with known NK-cell sensitive and -resistant lymphoid cell ines showed that the increased susceptibility is a result of the appearance of an NK sensitive target, rather than to a general increase in membrane fragility. Lymphocytes of EBV-seropositive and -negative donors were equally effective killers against P3HR-1 virus-superinfected targets. EBV-induced NK sensitivity increased with time. It was a result of some event associated with the intracellular viral cycle, and not to the adherence of viral particles to the cell surface. Induction of EBV-carrying P3HR-1 cells to entry into the viral cycle with n-butyrate also increased their NK sensitivity. A transforming, noncytopathic prototype strain of EBV, B95-8, failed to increase the susceptibility of theRaji cells to NK-lysis, although it had some effect on the Daudi line. Because NK cells can kill virus-producing cells at an early stage of the cycle, before the virus particles are assembled, they may restrict, in vivo, the spread of the virus from latently infected cells. PMID- 6244359 TI - Effect of noradrenaline and vanadium on Na+K+-activated ATPase in rat cerebral cortex synaptosomal preparation. AB - The effect of l-noradrenaline and vanadate on the activity of Na+K+-activated ATPase was studied on synaptosomal brain cortex preparation. Using neutron activation analysis it was found that the rat cerebral cortex synaptosomal preparation contains 0.16 microM vanadium. The concentration of vanadium needed to reduce enzyme activity by 50% proved to be 2 x 10(-6) M. Evidence has been provided that the increase by noradrenaline of enzyme activity in synaptosomal preparation depends on the presence of an inhibitory contaminant in commercial ATP preparations. In homogenate, however, noradrenaline was able to enhance enzyme activity even when vanadium-free ATP was used. This fact indicates that noradrenaline removes the inhibitory effect of cytoplasmic factor thereby stimulating enzyme activity. PMID- 6244361 TI - Preferential binding of 3,5-dimethyl-3'-isopropylthyroinine (DIMIT) to brain nuclear receptors for thyroid hormones. PMID- 6244360 TI - A rapid micro method for 2',3'-cyclic nucleotide 3'-phosphohydrolase assay using micro high performance liquid chromatography. PMID- 6244362 TI - Evidence against dopaminergic and further support for alpha-adrenergic receptor involvement in the pineal phosphatidylinositol effect. PMID- 6244363 TI - Morphological and biochemical studies on the cerebral cortex from reeler mutant mice: development of cortical layers and metabolic mapping by the deoxyglucose method. PMID- 6244364 TI - Substrate specificity of [3H]muscimol binding to a particulate fraction of a neuron-enriched culture of embryonic rat brain. PMID- 6244365 TI - Isolation of 2',3'-cyclic nucleotide 3'-phosphodiesterase from human brain. PMID- 6244366 TI - Improved method for purification of 2',3'-cyclic nucleotide 3'-phosphohydrolase from bovine cerebral white matter. PMID- 6244367 TI - Activities of enzymes synthesizing diacyl, alkylacyl, and alkenylacyl glycerophosphoethanolamine and glycerophosphocholine during development of chicken brain. PMID- 6244368 TI - Halothane increases membrane fluidity and stimulates sphingomyelin degradation by membrane-bound neutral sphingomyelinase of synaptosomal plasma membranes from calf brain already at clinical concentrations. PMID- 6244370 TI - Gangliosides containing glucosamine and galactosamine in transformed Tay-Sachs disease and normal human brain cell lines. AB - Human SV-40 transformed brain cell lines derived from Tay-Sachs disease (TSD) and normal fetal cerebra were grown in culture and analyzed for their ganglioside content. Both the TSD and normal cells contained GM3, GM2, and a novel triheoxyl N-acetylglucosamine-containing ganglioside. In order to increase tumorigenicity, the cells were cloned on soft agar. The cloned cells still contained GM3, GM2, and the N-acetylglucosamine-containing ganglioside. The per cent distribution of gangliosides in the TSD and normal SV-40 transformed cell lines was surprisingly similar despite the fact that the TSD transformed cells still lacked hexosaminidase A, the isoenzyme which is required to break down GM2. PMID- 6244369 TI - Late responses as aids to diagnosis in peripheral neuropathy. AB - The usefulness of performing late response studies for the detection of peripheral nerve dysfunction has been demonstrated. It has been shown that significant prolongation of the minimal latencies of the H reflex and the F response is present at a time when conventional methods of motor and sensory conduction do not show an abnormality in individual patients. Abnormalities of late responses have been shown to occur in a variety of peripheral neuropathies with "axonal" as well as "segmental demyelination" type of underlying pathology. PMID- 6244371 TI - Centronuclear myopathy with type I fibre hypotrophy and "fingerprint" inclusions associated with Marfan's syndrome. AB - The authors present results of histological and electron-microscopical investigations of muscular tissue obtained by biopsy from a 20-year-old man, who showed typical features of Marfan's syndrome associated with slowly progressive muscular weakness. The muscle showed a peculiar combination of centronuclear myopathy with hypotrophy of type I fibres and the so called "fingerprint myopathy". The combination of such myopathic phenomena with Marfan's syndrome presents a unique and hitherto undescribed condition. PMID- 6244372 TI - Ultrastructural study of the medulloblastoma in tissue culture. AB - The electron microscopic features of the early phases of growth of the medulloblastoma maintained in vitro are described. The predominant early growth is comprised of small migrating cells with large nucleocytoplasmic ratio, few organelles and prominent neuritic processes containing abundant microtubules. These cells compare favorably with the cells of the primitive external granular layer of the cerebellum and cells cultivated in vitro from the fetal cerebellar cortex previously described. In addition astrocytes containing 70 to 90 A cytoplasmic filaments were commonly found in these cultures. Undifferentiated cells and cells with cilia were present in the explant proper. Cells with processes containing large dense core vesicles were also present in the explant proper suggesting the presence of neuronal differentiation. Our studies support the concept that the medulloblastoma is derived from primitive neuroectodermal cells. In addition it also suggests that astrocytic and neuronal differentiation may occur in this neoplasm in vitro. PMID- 6244373 TI - Brain glycoprotein in tumours of the nervous system. AB - We studied various tumours of the nervous system by the immunofluorescence technique using an anti-brain specific alpha 2 glycoprotein antiserum (anti-NSA3 antiserum). We found the antigen in 24/27 astrocytomas and 4/4 oligodendrogliomas but in none of the 8 meningiomas tested. There was an identity between the astrocytoma/oligodendroglioma antigen and that of normal brain as shown by the immunoprecipitation technique. By the immunofluorescence technique using inhibition of the antiserum we demonstrated that the tumour antigen is devoid of some specific nervous system determinants present in normal brain. PMID- 6244374 TI - Topographic distribution of terminals of Ia and group II fibers in spinal cord, as revealed by postsynaptic population potentials. PMID- 6244375 TI - The energy requirement of the dental cutting process. AB - The results are presented of research into the efficiency of various forms of dental burs. This research was carried out at the Delft University of Technology in collaboration with the Subfaculty of Dentistry of the Free University of Amsterdam. The process efficiency was measured during burring of both human teeth and amalgam plugs, with diamond burs and tungsten carbide burs at different speeds and diameters of the bur. Only the efficiency of the cutting process was evaluated, disregarding a number of other essential aspects of the burring process, such as the remaining surface quality after burring and the vibrations generated during burring. PMID- 6244376 TI - Disseminated herpes simplex associated with H. influenzae infection in a previously healthy child. PMID- 6244377 TI - Parainfluenza type 3 parotitis in two immunodeficient children. PMID- 6244378 TI - The effect of ACTH therapy upon infantile spasms. AB - Fifty-five infants with infantile spasms and hypsarrhythmia, who were treated with ACTH using 80 units im every other day for a mean period of ten months, were studied retrospectively and showed better results than infants using so-called nonsteroidal anticonvulsants or ACTH and steroids in other doses and with other time intervals. The study showed that the treatment with ACTH within the first month of onset of spasms produced a higher incidence of spasm-free state while on treatment, a shorter duration of spasms while on treatment, and a higher incidence of spasm-free state while on treatment, a shorter duration of spasms while on treatment, and a higher incidence of a spasm-free state when off treatment, compared to a similar regimen of ACTH begun after seizures had persusted for more than a month. The value of early treatment of infantile spasms suggests that the treatment of this disease should be regarded as a medical emergency. PMID- 6244379 TI - Vincristine, dactinomycin, and cyclophosphamide (VAC) chemotherapy for recurrent metastatic Wilms tumor in previously treated children. PMID- 6244380 TI - Rotavirus: the first five years. PMID- 6244381 TI - In vivo evidence for defective activity of glucose-6-phosphatase in type IB glycogenosis. PMID- 6244382 TI - Vitamin D--resistant rickets: end-organ unresponsiveness to 1,25(OH)2D3. PMID- 6244383 TI - Adenocarcinoma of the colon following Wilms tumor. PMID- 6244384 TI - Antiasthmatic drug therapy and calcium ions: review of pathogenesis and role of calcium. AB - This paper presents the calcium-dependent pathophysiological features of allergic and nonallergic asthma. Various theories concerning the role of free calcium ions in the pathogenesis of asthma are discussed. PMID- 6244385 TI - Mechanism for the potentiation of oxygen toxicity by disulfiram. AB - Rats given disulfiram (200 mg/kg) or diethyldithiocarbamate (200 mg/kg) by intraperitoneal injection were exposed to 2 atmospheres absolute oxygen in a hyperbaric chamber or kept in normoxia. By 12 hr of hyperoxia exposure, none of the control but 30% of the disulfiram-treated and 87% of the diethyldithiocarbamate-treated rats had died. Both disulfiram and diethyldithiocarbamate administration decreased lung cytosolic superoxide dismutase activity, but the pharmacokinetics were different. At 1 hr postinjection of diethyldithiocarbamate superoxide dismutase activity was 40% decreased but returned to control activity within 13 hr (4 hr, 18% inhibited). In contrast, disulfiram administration produced a greater decrease at 4 hr (31%) than at 1 hr (16%) and was still effective at 13 hr (28% less than control). Although disulfiram did not produce as great a decrease at 1 hr as did diethyldithiocarbamate, it's effect was more persistent. In vitro, diethyldithiocarbamate inactivated superoxide dismutase at 10(-4) M, although 10( 3) M disulfiram did not cause any reduction in enzymatic activity. The contrast between the inhibition by disulfiram of lung superoxide dismutase activity in vivo and its lack of effect in vitro suggests metabolism of disulfiram to diethyldithiocarbamate. It is likely that disulfiram administration potentiates oxygen toxicity via in vivo reduction to diethyldithiocarbamate and subsequent inhibition of superoxide dismutase. PMID- 6244386 TI - Differential distribution of beta-1 and beta-2 adrenergic receptors in cat and guinea-pig heart. AB - The concentrations of beta-1 and beta-2 adrenergic receptors were determined in membranes prepared from the left ventricles and right atria of cat and guinea-pig hearts. The relative densities of the two receptor subtypes were determined by analyzing the kinetics of inhibition of specific [125I]iodohydroxybenzylpindolol binding by drugs previously found to show in vitro selectivity for beta-1 or beta 2 receptors. The right atria (including the sinoatrial node) from hearts of both species contained both beta-1 and beta-2 adrenergic receptors. Although beta-1 receptors predominated, approximately one-quarter of the beta adrenergic receptors in the atria were of the beta-2 subtype. The ventricles contained essentially only beta-1 adrenergic receptors. The densities of beta-1 and beta-2 adrenergic receptors were similar in the atria from both species. The cat left ventricle, however, contained twice as many receptors of the beta-1 type than did the ventricle of the guinea-pig heart. These results may explain previous findings that beta-2 selective drugs have more of an effect on chronotropy than on inotropy. PMID- 6244387 TI - Cholinergic, adrenergic and purinergic response of sequential strips of rabbit urinary bladder. AB - In this study, we have characterized the response of five sequential segments of urinary bladder to cholinergic, adrenergic, and purinergic agonists. The results indicate that an abrupt alteration in pharmacological response between bladder body and base occurs at the level of the ureteral orifices. The bladder body responds preferentially to urecholine (muscarinic cholinergic), isoproterenol (beta adrenergic) and ATP (purinergic), whereas the bladder base responds perferentially to methoxamine alpha adrenergic). In parallel studies, the density of both muscarinic cholinergic receptors ([3H]quinuclidinyl benzilate binding sites) and beta adrenergic receptors were significantly higher in the body than in the base, whereas the concentration of alpha adrenergic receptors was greater in the bladder base than in the body. From these studies, we conclude that the differences in the response of the bladder base and body to cholinergic and adrenergic agents are primarily due to differences in the densities of the specific autonomic receptors. In addition, the response of the bladder to ATP (which is a putative neurotransmitter in the urinary bladder) can also be separated between body and base. The distribution is similar to that observed for urecholine. PMID- 6244388 TI - Alteration of synaptic membrane fatty acid composition and anesthetic requirement. AB - Mice fed a saturated, Purina chow or unsaturated fat diet from birth have different synaptic membrane fatty acid compositions. The saturated diet decreased docosahexaenoic [22:6 (n - 3)] and increased eicosatrienoic [20:3 (n - 9)], docosatrienoic [22:3 (n - 9)] and docosapentaenoic [22:5 (n - 6)] fatty acids compared to the Purina chow or unsaturated fat diet. The most notable alterations occurred in the synaptic membrane phosphatidylserine and phosphatidylethanolamine fractions. The saturated diet also caused a minor increase in oleic acid [18:1 (n - 9)i1. Animals fed the saturated diet showed a small, significant decrease in nitrous oxide ED50 (dose required to abolish the righting reflex in half the animals) but not in isoflurane ED50, compared to animals fed the Purina chow or unsaturated fat diet. Thus, large alterations in several synaptic membrane fatty acid components have little or no influence on anesthetic requirement. PMID- 6244389 TI - beta Adrenergic receptor-mediated regulation of cyclic nucleotide phosphodiesterase in C6 glioma cells: vinblastine blockade of isoproterenol induction. AB - Persistent stimulation with isoproterenol of the beta adrenergic receptor located in C6 glioma cell membranes results in a rapid rise in the cyclic AMP content, an activation of soluble cyclic AMP-dependent protein kinase, a translocation of catalytic subunits of the activated protein kinase to the nucleus and a delayed (3--4 hr later) increase of cyclic AMP phosphodiesterase activity and beta-nerve growth factor content. The phosphodiesterase increase requires new RNA and protein synthesis. A pretreatment of the cells with vinblastine in doses that fail to change protein synthesis blocks the increase in phosphodiesterase activity elicited by isoproterenol: the ED50 of vinblastine for this effect is 2.6 x 10(-7) M. In contrast, the simultaneous increase in beta-nerve growth factor content elicited by isoproterenol is not blocked by vinblastine and does not require new RNA and protein synthesis. We conclude that intact microtubules are required to transfer the catalytic subunits of activated protein kinase from cytosol to the nucleus. Hence microtubules may be operative in facilitating communication between the cell membrane and the nucleus. PMID- 6244390 TI - Naloxone-induced increases in serum luteinizing hormone in the male: mechanisms of action. PMID- 6244391 TI - Vanadate inhibits renin secretion from rat kidney slices. PMID- 6244392 TI - The effect of lithium on noradrenaline-induced cyclic AMP accumulation in rat brain: inhibition after chronic treatment and absence of supersensitivity. AB - Lithium (Li) has been reported to inhibit numerous adenylate cyclases, but often these reports used clinically toxic concentrations of Li and their relevance to a theory of Li action was questionable. The present report demonstrated Li inhibition beginning at 2 mM of the norepinephrine (NE)-induced cyclic AMP accumulation in a resuspended P2 pellet containing intact synaptosomes and in slices from rat cortex. The inhibition is demonstrable with isoproterenol as well and in the presence of a phosphodiesterase inhibitor. In cortical slices removed from rats treated for 21 days with therapeutically equivalent Li serum levels, NE induced cyclic AMP accumulation is inhibited by over 70%. After cessation of 21 or 42 days of Li treatment, an enhancement of cyclic AMP accumulation to NE is not demonstrable. Rubidium and cesium do not inhibit NE-induced cyclic AMP accumulation. These ions cause an increase in basal cyclic AMP accumulation in the absence of NE, as does Li to a lesser degree. The effect of Li to inhibit NE induced cyclic AMP accumulation is therefore specific to the Li ion, occurs at therapeutically equivalent concentrations, continues after chronic treatment and does not cause a compensatory supersensivity in the manner of the NE-receptor blocking drugs. PMID- 6244393 TI - Diuretic and vasoconstrictor effects of sodium orthovanadate on the isolated perfused rat kidney. AB - Sodium orthovanadate (vanadate) is a powerful inhibitor of (Na+,K+) adenosine triphosphatase and exhibits widespread actions on the renal and cardiovascular systems. In the present study, the effect of vanadate on the functions of the isolated perfused rat kidney was studied. The control parameters for this preparation were: glomerular filtration rate, 225 microliter/min; urine flow, 40 microliter/min; fractional sodium reabsorption, 92%; and total peripheral resistance, 765 kilo pascals/l/min. Varying concentrations of vanadate in the perfusate (0 to 32 microM) produced a dose-dependent rise in glomerular filtration rate, urine flow, total peripheral resistance and inhibition of sodium reabsorption. At higher concentrations, vanadate was nephrotoxic. Since vanadate produces simultaneous rises in glomerular filtration rate and total peripheral resistance, a postcapillary vasoconstrictor effect for the anion is postulated. Clearance of vanadate from the perfusate was determined at various concentrations of the anion in the perfusate and the reversibility of vanadate effect on the kidney was studied. In conclusion, vanadate is a potent diuretic, natriuretic and vasoconstrictor in the isolated, perfused rat kidney and is nephrotoxic at higher dose levels. PMID- 6244395 TI - The resolution of school phobia through family therapy. PMID- 6244396 TI - Voodoo--myth or mental illness? PMID- 6244394 TI - Inhibition of transmitter release in bullfrog sympathetic ganglia induced by gamma-aminobutyric acid. AB - 1. Effects of gamma-aminobutyric acid (GABA) on the nicotinic synapses in bullfrog sympathetic ganglia were studied. 2. When GABA (100 microM--1 mM) was applied to the ganglion, the post-synaptic membrane depolarized slightly and transiently with a slight decrease in the membrane resistance. 3. GABA (5 microM- 1 mM) decreased the amplitude of the fast excitatory post-synaptic potentials (fast e.p.s.p.) and its quantal content without a significant change in the quantal size, and these effects were seen even after the subsidence of the membrane depolarization. Picrotoxin (10 microM) did not antagonize the GABA action. 4. The sensitivity of the subsynaptic membrane to ACh was unaffected by GABA. On the other hand, the synaptic current underlying the fast e.p.s.p. was significantly depressed in the presence of GABA. 5. Neither the frequency nor the amplitude of the miniature e.p.s.p.s which occurred spontaneously were altered by GABA, in either normal or high K+ solutions. 6. The depressant action of GABA on the fast e.p.s.p. was not changed in a high K+ solution, while it was markedly decreased in a Cl- -deficient solution. 7. A small, but significant reduction in the amplitude of the presynaptic terminal spike recorded with a focal extracellular electrode was observed under the effect of GABA. 8. It was concluded that GABA inhibits synaptic transmission of bullfrog sympathetic ganglion mainly by decreasing the evoked release of transmitter and only partly by post-synpatic action. Possible mechanisms of the presynaptic action of GABA were discussed. PMID- 6244397 TI - Expanding the role of nurses in child abuse prevention and treatment. PMID- 6244399 TI - A systematic approach to selecting group participants. PMID- 6244398 TI - The process of termination. PMID- 6244400 TI - Suicide: a case for investigation. PMID- 6244401 TI - Hopelessness and helplessness. PMID- 6244402 TI - It's O.K. to cry: feeling outlets for mentally retarded children. PMID- 6244403 TI - From "lunatic" to "client": 300 years of psychiatric patienthood. PMID- 6244404 TI - Caffeine consumption and sleep disturbance in acutely ill psychiatric inpatients. PMID- 6244405 TI - Reminiscence, self-esteem and self-other satisfaction in adult male alcoholics. PMID- 6244406 TI - In-vitro contractility of rat seminiferous tubules in response to prostaglandins, cyclic GMP, testosterone and 2,4'-dibromoacetophenone. AB - The effects of prostaglandin (PG) F-2 alpha and E-2, cyclic GMP, testosterone and 2,4'-dibromoacetophenone (DBA) on rat seminiferous tubules in vitro were ascertained by measuring contractile frequency, size of contractions and tone (tubular diameter). PGF-2 alpha (10(-9)--10(-5) M) increased frequency and tone but not magnitude of contraction. Contraction frequency and tone were decreased by PGE-2 (10(-9)--10(-5) M) but the size of contractions was again unaffected. Cyclic GMP (10(-10)--10(-6) M) increased the frequency of contractions and tone and decreased size of contractions. Testosterone decreased the frequency and size of contractions and increased tone at concentrations of 10(-9) to 10(-7) but higher concentrations (10(-6) M) reversed these changes. DBA (10(-7)--10(-3) M) greatly decreased the frequency and size of contractions and tone and spontaneous contractions were abolished at 10(-3) M. Our data strongly suggest that PGs, cyclic nucleotides and testosterone are all important in vivo in modulating contractility of seminiferous tubules and as such would participate in sperm transport from the testes. PMID- 6244408 TI - Ultrastructure of tumoricidal peritoneal exudate cells stimulated in vivo by perfluorochemical emulsions. PMID- 6244409 TI - Enhanced cytotoxicity of mouse natural killer cells for vaccinia and herpes virus infected targets. PMID- 6244407 TI - Fetal adrenal steroidogenesis: drug effects in sheep. AB - The influence of ACTH (100 pg/ml), ethanol (10(-3)/M) and morphine (10(-6)/M) on the rate of formation of cholesterol and various steroids in female fetal adrenal tissue was studied in vitro. ACTH and ethanol had no effect on corticosterone formation, while morphine increased it significantly (0.586 +/- 0.049 to 0.799 +/ 0.027 microM/mg protein) (P less than 0.02). Cholesterol formation was increased significantly by ethanol (from 0.103 +/- 0.079 to 0.248 +/- 0.035 microM/mg protein) (P less than 0.01) but not by morphine. Both ethanol and morphine significantly decreased testosterone synthesis (from 0.079 +/- 0.043 to 0.019 +/- 0.002 and 0.006 +/- 0.003 microM/mg protein, respectively) (P less than .01, less than .001). Adrenocortical formation of 17-beta estradiol was similarly attentuated by both ethanol (from 0.372 +/- 0.056 to 0.948 +/- 0.024 microM/mg protein) and morphine (to 0.600 +/- 0.020 microM/mg protein). Adrenocortical pregnanediol formation was significantly decreased by both ethanol (50%; P less than .01) and morphine (36%; P less than .02). Thus, the effect of ethanol and morphine on testosterone, estradiol and pregnanediol was similar and consisted of suppression. The effects of these agents upon corticosterone and cholesterol formation were different. Ethanol, like ACTH, did not stimulate corticosterone formation, but such stimulation did occur with morphine. Ethanol, but not morphine, stimulated cholesterol formation. The data suggest that agents capable of placental transport affect the formation of adrenocortical hormones in the fetal adrenal. PMID- 6244410 TI - Aminoglycoside antibiotics. 3. Epimino derivatives of neamine, ribostamycin, and kanamycin B. AB - 2',3'-Epimino analogues of neamine, ribostamycin, and kanamycin B possessing little or no intrinsic antimicrobial activity were designed to enhance the activity of kanamycin A against bacterial strains that elaborate aminoglycoside 3'-phosphotransferases. Routes were devised for their synthesis from the parent antibiotics and the 2'',3''-epimino analogue of kanamycin B also was prepared. None of these analogues was active against phosphotransferase-producing bacteria, although the kanamycin B derivatives showed very weak activity against nonresistant strains. At 8 and 32 microgram/mL, the 2',3'-epimino analogue of neamine produced a small synergistic effect on the activity of kanamycin A against a strain of Escherichia coli that produces aminoglycoside 3' phosphotransferase II. The N3-(carbobenzyloxy) derivative of this analogue produced a small effect against the same strain, and it, as well as the 2'',3'' epimino analogue of kanamycin B, slightly enhanced the activity of kanamycin A against a strain of Proteus rettgeri that elaborates a similar enzyme. PMID- 6244412 TI - Na+ and H+ dependent Mn2+ binding to phosphatidylserine vesicles as a test of the Gouy-Chapman-Stern theory. PMID- 6244411 TI - Synthesis and biological activities of 5-(hydroxymethyl, azidomethyl, or aminomethyl)-2'-deoxyuridine and related 5'-substituted analogues. AB - The synthesis of 5-(azidomethyl)-2'-deoxyuridine (10) has been accomplished by two independent methods. The first involved tosylation of 5-(hydroxymethyl)-2' deoxyuridine (1) to furnish a mixture of two mono- and a ditosyl nucleosides which were converted into the corresponding 5-(azidomethyl) (10), 5-(azidomethyl) 5'-azido (14), and 5-(hydroxymethyl)-5'-azido (15) derivatives of 2' deoxyuridine. The second method was more selective and required the formation of the intermediate 5-(bromomethyl)-3',5'-di-O-acetyl-2'-deoxyuridine (8), followed by displacement of the bromo group by lithium azide and deacetylation. Catalytic hydrogenation of the azides 9, 10, 14, and 15 gave the corresponding amines 16, 2, 6, and 7, respectively. Compounds 1, 2, 10, and 16 inhibited the growth of murine Sarcoma 180 and L1210 in culture, and the activity of 2 was prevented by 2'-deoxypyrimidine nucleosides but not by purine nucleosides. The replication of herpes simplex virus type 1 (HSV-1) was strongly inhibited only by 1 and 10. Studies on the binding of the various thymidine analogues to HSV-1 encoded pyrimidine deoxyribonucleoside kinase indicate that 1 and 10 have good affinity for the enzyme. PMID- 6244413 TI - Dimensions of active cytochrome c oxidase in reconstituted liposomes using a gold ball shadow width standard: a freeze-etch electron microscopy study. PMID- 6244414 TI - Prophylaxis of bacteriuria during intermittent catheterization of the acute neurogenic bladder. AB - A randomized prospective study of bacteriuria control during early intermittent bladder catheterization was performed on a spinal cord injury service. The 64 male subjects underwent 16,620 catheterizations and had 83 significant episodes of infection. The infection rates among various groups were compared: 1) control patients, 2) patients treated with intravesical neomycin/polymyxin-B, 3) patients given low dose daily macrocrystals of nitrofurantoin and 4) patients given intravesical treatment and oral nitrofurantoin. There was significant reduction in infection rates when oral and intravesical antibiotics were used. PMID- 6244415 TI - Mucinous adenocarcinoma probably arising in the renal pelvis and ureter: a case report. AB - A patient with widely disseminated mucinous adenocarcinoma had polypoid tumors in the left renal pelvis and ureter. While no certain primary site was determined, either clinically or at postmortem examination, microscopic examination of the left renal pelvis and ureter revealed atypical glandular metaplasia adjacent to the tumors and made the upper urinary tract a likely site of origin for the adenocarcinoma. PMID- 6244416 TI - Herpes viruses induce atherosclerosis in chickens. PMID- 6244417 TI - Tricyclic antidepressants for peripheral neuropathy. PMID- 6244418 TI - delta 9-Tetrahydrocannabinol for refractory vomiting induced by cancer chemotherapy. AB - Fifty-three patients receiving antineoplastic chemotherapy who had experienced severe nausea and vomiting refractory to standard antiemetic agents were treated with delta 9-tetrahydrocannabinol (THC). These patients were given THC 8 to 12 hours before, during, and for 24 hours after chemotherapy. Ten patients (19%) had no further nausea and vomiting; 28 (53%) had at least a 50% reduction of nausea and vomiting compared to previous courses with the same agents. No appreciable reduction of nausea and vomiting was seen in 15 patients (28%). Toxic reactions were generally mild, with only four patients experiencing reactions that necessitated stopping THC therapy. We suggest that, since THC is a useful antimetic agent in patients having refractory chemotherapy-induced vomiting, existing restrictions prohibiting its therapeutic use should promptly be eased. PMID- 6244419 TI - Marijuana for drug-induced nausea and vomiting. PMID- 6244420 TI - Autoantibodies may cause bronchospasm in adults. PMID- 6244421 TI - Influenza in children. Relationship to other respiratory agents. AB - During the 1975-1976 respiratory disease season, influenza A/Victoria virus exceeded respiratory syncytial (RS) virus as a cause of lower respiratory tract disease (LRD) in children admitted to the hospital. This was a reversal of their usual roles in the etiology of LRD; however, the importance of influenza viruses in causing serious disease in children has been underestimated because of failure to appreciate the full spectrum of disease associated with influenza virus infections. In addition to those with LRD, several children were hospitalized with nonspecific febrile illnesses or CNS involvement. Furthermore, in the ambulatory care setting, influenza viruses were the most important cause of illness that necessitated children's being brought for medical care during a three-year period. During the peak of epidemics, influenza viruses appeared to interfere with the spread of other major respiratory viruses--particularly RS virus. PMID- 6244422 TI - Cytomegalovirus-associated gastritis in a compromised host. PMID- 6244423 TI - Hepatitis B antigen associated with cryoglobulinemia, peripheral neuropathy, and myopathy. PMID- 6244424 TI - [The experience of primary tracheal tumor (author's transl)]. PMID- 6244425 TI - Insulinoma. PMID- 6244426 TI - [A nurse's experiences in an ambulatory after care group for alcoholics]. PMID- 6244427 TI - [Nurses, as "they" want them]. PMID- 6244428 TI - [Towards normal development of terminally ill children]. PMID- 6244429 TI - [Entry into the profession of nursing]. PMID- 6244430 TI - [Balint groups for nurses]. PMID- 6244431 TI - [What did you learn from the Balint group?]. PMID- 6244432 TI - [Reasons why registered nursing personnel quits]. PMID- 6244433 TI - [A child in the hospital remains a child. Introduction of the theme]. PMID- 6244434 TI - [Personnel shortage and what the Association can do about it]. PMID- 6244435 TI - [Impressions from the medical refugee center in the Renner Hospital, Bern]. PMID- 6244436 TI - [A child in the hospital remains a child. Observations on patient care planning]. PMID- 6244437 TI - [Survey of cases of child abuse in Switzerland. From an examination study done at the School for Social Studies of St. Gall, 1979]. PMID- 6244438 TI - [World Health Organization: current aspects of viral hepatitis surveillance]. PMID- 6244440 TI - [Observations on health and the orientation of nursing care]. PMID- 6244439 TI - [Experience of a nurse in the Army medical service. Reception of Vietnamese refugees in the Jenner Hospital in Bern]. PMID- 6244441 TI - [Nurses, as "they" want them]. PMID- 6244442 TI - [A nurse reports from the USA]. PMID- 6244443 TI - [The school in the practice field from the viewpoint of an advisory position]. PMID- 6244444 TI - [Response letter to Dr. Leemann (Nursing staff shortage from the viewpoint of a hospital physician]. PMID- 6244445 TI - [Reasons for quitting: considerations of 2 nurse supervisors]. PMID- 6244446 TI - [In memoriam Matron Dr. Lydia Leemann]. PMID- 6244447 TI - [Reflection]. PMID- 6244448 TI - [Nurse, I'm in pain!]. PMID- 6244449 TI - [History of a betrayal]. PMID- 6244450 TI - [Client-caretaker relations]. PMID- 6244451 TI - [Nursing care and the mentally handicapped]. PMID- 6244452 TI - [In the Loex House: SOS in search of nurses!]. PMID- 6244453 TI - [Reflections around a fire: there is nobody at home here]. PMID- 6244455 TI - [More rational utilization of nursing personnel]. PMID- 6244454 TI - [The paradox of feminine aging: a risk or a blessing]. PMID- 6244456 TI - [A nurse consultant visits the Swiss Nurses' Association]. PMID- 6244457 TI - [Primary health care]. PMID- 6244458 TI - [What is research and how can it serve in the field of nursing services?]. PMID- 6244459 TI - [WHO and ICN: statements on primary health care]. PMID- 6244460 TI - [Our role in the promotion of primary health care]. PMID- 6244461 TI - [Psychological and social stresses of nursing personnel]. PMID- 6244462 TI - In vitro studies of thromboresistance: the role of prostacyclin (PGI2) in platelet adhesion to cultured normal and virally transformed human vascular endothelial cells. AB - Circulating blood platelets normally do not adhere to, or aggregate on, the vascular endothelial lining. We have developed an in vitro model system to study the mechanisms of endothelial resistance to platelet adhesion, and to determine the role of prostacyclin (PGI2) in this process. This system combines scanning electron microscopy and measurement of bound (3H)-adenine-labeled platelets to examine platelet adhesion to primary cultures of human endothelial cells, which generate PGI2-like activity, and to virally transformed endothelial cells, which lack this activity. Under basal conditions primary cultures bound less than one platelet per cell (228 +/- 8 c.p.m. per 10(4) cells, mean +/- standard error of the mean). Inhibition of endothelial PGI2 production by 50 microM aspirin or 2.8 microM indomethacin did not result in a significant change in platelet adherence. Stimulating prostaglandin production with arachidonic acid, or adding exogenous PGI2 did not depress platelet adhesion below the basal levels observed with untreated cultures. In contrast ot primary cultures, transformed endothelium showed markedly increased platelet adherence (3,993 +/- 194 c.p.m. per 10(4), mean +/- standard error of the mean), in the form of single platelets and clusters of two to five nonaggregated platelets. Although exogenous PGI2 was effective in hibiting platelet adherence to these transformed cells, even pharmacologic doses (1 microgram. per ml.) did not depress adhesion to the basal levels associated with normal cells. These results suggest that endothelial properties essential to blood compatibility are altered by viral transformation, and further, that generation of PGI2 by normal endothelium is not the key factor which prevents platelet adherence to the intact vessel wall. PMID- 6244464 TI - Kinetics of oxygen in peritoneal cavity. Effects of chemical peritonitis and intraperitoneally administered colloids in rats. PMID- 6244463 TI - The effect of portacaval shunt upon hepatic cholesterol synthesis and cyclic AMP in dogs and baboons. PMID- 6244465 TI - The angiotensin converting enzyme in pulmonary sarcoidosis and the relative diagnostic value of serum lysozyme. PMID- 6244466 TI - Acute myocardial infarct scintigraphy with infarct-avid radiotracers. AB - The selective uptake of radiopharmaceuticals by acutely infarcted myocardium has emerged as an independent, noninvasive technique to aid in the detection, localization, and quantification of myocardial necrosis. PMID- 6244467 TI - Benign eccrine cylindroma of the external auditory canal. AB - The benign eccrine cylindroma is one of a number of histologically different tumors of the external auditory canal that have been grouped by some as "ceruminomas." The eccrine cylindroma, malignant apocrine gland tumors, and the adenoid cystic carcinomas of salivary gland origin are distinctly different histologically and in natural history and prognosis. Therapy should, therefore, be tailored to the specific tumor. A patient is presented who developed an asymptomatic external auditory canal mass that was initially incompletely excised. A recurrence five years later again proved to be a benign eccrine cylindroma of sweat gland origin. Successful and adequate treatment was local excision with a cuff of normal tissue. A variety of tumors originating from the adnexal skin structures may appear in the external auditory meatus and canal. Treatment must include biopsy and close consultation with the pathologist. The term cylindroma has been loosely applied to both benign and malignant glandular neoplasms but its usage should be restricted to the specific benign eccrine cylindrome herein described. A rationale of therapy is presented. PMID- 6244468 TI - Tonsillar metastasis from carcinoma of the breast with ultrastructural and steroid receptor analyses. AB - An unusual site of metastasis for mammary carcinoma is presented with an examination of the tumor's histologic and ultrastructural features, as well as its estrogen and progesterone receptor protein content. The importance of careful examination of the tonsillar area is emphasized in this patient in whom the tonsillar metastasis represented the initial indication of breast tumor recurrence. Estrogen and progesterone receptor analyses are utilized both as an aid in identifying the origin of the metastatic tumor focus as well as an aid in selecting therapy. PMID- 6244470 TI - Rapid inhibition by cycloheximide of rat hepatic nuclear free and engaged poly(A) polymerase activities. PMID- 6244469 TI - Estrogen receptors in nasopharyngeal angiofibromas. AB - Nasopharyngeal angiofibromas, which occur exclusively in pubescent males, are frequently treated with estrogens in an effort to decrease their size and vascularity. It has been presumed by some that estrogen has a direct effect on the tumor itself. Others have felt that hormone acts by affecting the pituitary gonadal axis. In this study, six male patients with nasopharyngeal angiofibromas had their tumors analyzed for estrogen receptors and none were found. Despite this fact, two of these patients treated with estrogens showed clinical evidence of a decrease in tumor size and vascularity. This response occurring in the absence of estrogen receptors suggests that the action of estrogen on nasopharyngeal angiofibromas is indirect. Alternatively these tumors may be testosterone dependent and the administration of estrogen suppresses the normal male testosterone levels, with a resultant reduction in tumor size and vascularity. Twenty-four patients with nasopharyngeal angiofibroma have been treated at the University of Virginia in the past 22 years. The average blood loss at operation was 1900 cc. When estrogens were administered preoperatively in 3 patients, the average blood loss was 1135 cc. Those patients who received no estrogens averaged 2000 cc blood loss. These figures do not reflect the size or extent of the disease, both of which greatly influence blood loss. PMID- 6244471 TI - Effects of prostaglandins E1, E2 and F2 alpha on the cardiac chronotropism by affecting the cardiac ganglionic transmission in spinal dogs. PMID- 6244472 TI - Effects of chronic ethanol ingestion on glucose homeostasis in males and females. PMID- 6244473 TI - Characterization of alpha-adrenergic receptor subtypes in rat brain: estimation of ability of adrenergic ligands to displace 3H-dihydroergocyrptine from the receptor subtypes. PMID- 6244474 TI - Distribution of phosphoinositides among subfractions of rat brain myelin. AB - Rat brain myelin was separated into three subfractions, heavy, medium, and light, and the concentrations of phosphatidic acids (PA), phosphatidylinositol (PI), di- (DPI), and triphosphoinositide (TPI) in these fractions were determined. PI was evenly distributed among the fractions, and PA, DPI, and TPI occurred in highest concentrations in the "light" myelin. This result indicates that these fast metabolizing lipids play an important role in the tightly packed central lamellae of the myelin sheath. PMID- 6244475 TI - Microsomal phosphatidic acid phosphohydrolase of rat mammary tissue: I. General properties. AB - The microsomal bound phosphatidic acid phosphohydrolase from lactating rat mammary tissue had a specific activity of six nmoles per mg protein per minute. The optimum pH was 7.0; magnesium at 1.3 mM was required for maximum activity, and at low substrate concentrations magnesium lowered the Km of the enzyme for phosphatidic acid. Diglycerides exerted little effect while diglyceride ether stimulated enzyme activity. Inorganic salts, i.e., potassium phosphate and potassium chloride, enhanced rates of phosphatidic acid hydrolysis under standard assay conditions. PMID- 6244476 TI - [Local lesions after the interstitial administration of colloidal 198Au]. PMID- 6244477 TI - Cranial nerve involvement in systemic sclerosis (scleroderma): a report of 10 cases. AB - Ten patients with the diagnosis of systemic sclerosis developed cranial nerve involvement. A trigeminal sensory neuropathy evolved insidiously in all patients and in five of these it was a presenting complaint. The glossopharyngeal nerve was involved in one patient. Taste was impaired in one patient and a unilateral loss of taste with fasciculations of the tongue were noted in another. Tinnitus was a complaint in three patients, two of whom had bilateral impairment of hearing. Facial weakness was noted in five patients. In three, this weakness was bilateral, while in the others the weakness was unilateral, and a past history of acute onset was obtained. The microangiopathy of systemic sclerosis is felt to be primarily responsible for these neurological deficits. The deposition of fibrous tissue may be a secondary phenomenon and contribute to the process by compression of nerves. PMID- 6244478 TI - Growth of poliovirus in HeLa cells persistently infected with HVJ (Sendai virus). AB - The growth of poliovirus in a HeLa cell culture persistently infected with the hemagglutinating virus of Japan (HVJ, the Sendai strain of parainfluenza 1 virus) (HeLaHVJ) was studied. Plaques produced by poliovirus on HeLaHVJ cell monolayers were hazier, smaller and fewer than those on HeLa cells. HeLaHVJ cells were indistinguishable from normal HeLa cells with respect to adsorption rate and penetration efficiency of poliovirus. Extracellular yields of poliovirus in HeLaHVJ cells were lower, and the cytopathic changes were less than those in normal HeLa cells, while cell-associated virus growth in HeLaHVJ cells was nearly equal to that in HeLa cells. HeLaHVJ cells responded more effectively to the action of magnesium chloride, which facilitates virus release from infected cells, resulting in an cytopathic effects. No reduction in poliovirus yield could be detected in HeLa cells acutely infected with HVJ. The relationship between the inhibition of the release of poliovirus from HeLaHVJ cells and the persistent infection of the cells with HVJ is discussed. PMID- 6244479 TI - Characterization of forespores isolated from Bacillus subtilis at each stage of sporulation. PMID- 6244480 TI - Seasonal pattern in childhood viral lower respiratory tract infections in Melbourne. AB - Respiratory syncytial virus and parainfluenza viruses are the major pathogens in acute lower respiratory infection in infants and younger children. They show distinct seasonal patterns. An annual epidemic of respiratory syncytial virus infection is seen in Melbourne and this coincides with the coldest months of the year. Parainfluenza virus Type 1, the most frequent cause of laryngotracheobronchitis, occurs as an autumn epidemic every second year. Parainfluenza virus Types 2 and 3 are present most years and do not show a clear seasonal pattern. PMID- 6244481 TI - Cytomegalovirus retinitis. AB - The appearances of cytomegalovirus retinitis are described in a body who was receiving maintenance immunosuppressive therapy for lymphatic leukaemia. The retinitis improved on cessation of the treatment and settled completely after an injection of lymphocyte dialysable transfer factor. PMID- 6244482 TI - Further studies on neonatal rotavirus infections. AB - Forty newborn babies who were shown to be excreting rotaviruses within a few days of birth were tested daily for one month. Most were found to excrete virus for only a short period of time. In 48% of babies, virus was found on one day only, in 25% it was present for two days, and in 10% for three days. Most of these infections did not appear to confer lasting immunity. Only 21% of young children who excreted virus as neonates had detectable circulating complement-fixing antibodies when eight to eighteen months old. A survey of newborn babies showed that 89% of babies possessed the antibody, but, by the age of four to six months, the antibody was present only in 7%. This supports the view that infected neonates fail to develop circulating complement-fixing antibodies. Infection rates did not differ significantly between breast-fed and bottle-fed babies. Likewise, maternal antibody levels could not be shown to have any effect on infection. No rotavirus particles were found in breast milk. PMID- 6244483 TI - Immunologic properties of protein-linopolysaccharide complexes--III. Role of carbohydrate in the LPS adjuvant effect. PMID- 6244484 TI - [Therapeutic trial with a fragment of ACTH (ACTH 4-10) in early childhood epilepsy (author's transl)]. AB - Epilepsy in early childhood has been treated successfully with ACTH. However, side effects were significant due to the stimulation of the adrenal cortex by high doses of ACTH over a long time. It has been suggested, that ACTH does not influence the seizures via the adrenal cortex. Therefore we administered an ACTH fragment (ACTH 4-10) which does not influence the adrenal cortex. Seven children aged between 8 months and 13 1/2 years were treated at least for 3 weeks with doses from 15 mg twice daily to 12 x 30 mg/day. Adrenal stimulation did not occur as proven by normal circadian plasma cortisol levels. However, the EEG regularly repeated, did not show improvements. The frequency of seizure was not reduced. It is concluded that this ACTH fragment (ACTH 4-10) does neither influence the adrenal cortex nor the EEG nor the frequency of seizures in early childhood epilepsy. PMID- 6244485 TI - Damage and repair in mammalian cells after exposure to non-ionizing radiations. II. Photoreactivation and killing of rat kangaroo cells (Potorous tridactylus) and Herpes simplex virus-1 by exposure to fluorescent "white" light or sunlight. AB - Photoreactivation (PR) of ultraviolet (254 nm)-inactivated cornea cells of the potoroo (or rat kangaroo; Potorous tridacylus) has been studied at wavelengths greater than 375 nm from either fluorescent "white" light or sunlight. In both cases the PR kinetics curves pass through maxima, which most likely result from the superposition of concomitant inactivation by the photoreactivating light. The inactivating effect of light was directly demonstrated for non-UV-irradiated cells, permitting correction of the PR curves. Wavelengths greater than 475 nm, and even greater than 560 nm, which do not noticeably damage cells, still photoreactivate, though less effectively than shorter wavelengths. Light treatment of UV-inactivated Herpes simplex Virus-1 (HSV-1) after infection leads to PR effects resembling those observed for cells, while light treatment of unirradiated virus after infection likewise causes inactivation. The "fluence reduction factor" of PR, which is greater than 3 for the virus, exceeds that for the cells, where it decreases with increasing UV fluence. In vitro tests have indicated that sunlight greater than 375 nm causes photorepairable DNA lesions which are virtually fully repaired by the same light. Thus cell inactivation resulting from these solar wavelengths must be due to non-photorepairable damage. PMID- 6244486 TI - Binding and mutagenicity studies with 2-nitrosofluorene on Salmonella typhimurium TA98 grown at different temperatures. AB - The growth temperature of the histidine auxotroph Salmonella typhimurium TA98 influences the extent of binding of 2-nitrosofluorene (NOF) to this bacterium as well as the mutagenicity of this chemical carcinogen. Gas-liquid chromatography (GLC) of bacteria grown at 37, 27 and 17 degrees C revealed that the unsaturated (hexadecenoic plus octadecenoic) fatty-acid content increased from 15.0% at 37 degrees C to 20.5% at 27 degrees C and to 22.2% at 17 degrees C. It has been shown using both artificial and natural mammalian membranes that NOF adds to carbon-carbon double bonds in unsaturated fatty acids via an "Alder-ene" type reaction to produce a nitroxyl free radical adduct (N-O-LAF). The same adduct was formed when NOF was incubated with Salmonella typhimurium TA98. There was an increase in N-O-LAF formed in bacteria grown at 27 degrees C as compared to those grown at 37 degrees C, but very little formed in bacteria grown at 17 degrees C. Therefore the amount of N-O-LAF formed did not correlate with unsaturated fatty acid content. 14C-labeled NOF uptake in bacteria grown at different temperatures showed a good correlation with mutagenicity data. PMID- 6244487 TI - Molecular mechanisms involved in the production of chromosomal aberrations. II. Utilization of Neurospora endonuclease for the study of aberration production by X-rays in G1 and G2 stages of the cell cycle. AB - Chinese hamster ovary cells (CHO) were X-irradiated in G1 and G2 stages of the cell cycle and subsequently Neurospora endonuclease (NE) (E.C.3.1.4), an enzyme which is specific in cleaving single-stranded DNA, was introduced into the cells, after making the cells permeable by treatment with inactivated Sendai virus. With this treatment all classes of X-ray-induced chromatid aberrations increased in G2 cells, whereas in G1 cells an increase in chromosome type of aberrations was found, associated with a profound induction of chromatid type of aberrations as well. Duration of the availability of single-strand gaps for the action of NE has been studied in G2 cells following X-irradiation and the influence of different parts of the G2 stage on the type and frequencies of chromatid aberrations was discerned. While the increase in chromosome type of aberrations by NE in X irradiated G1 cells has been interpreted as due to the conversion of DNA single strand breaks or gaps to double-strand breaks by NE, the induction of chromatid aberrations in G1 has been assumed to be due to conversion of some of the damaged bases into strand breaks by NE. Biochemical evidence is presented for the conversion by NE of DNA single-strand breaks induced by X-rays into double-strand breaks using neutral sucrose gradient centrifugation. PMID- 6244488 TI - Studies on the influence of photoreactivation on the frequencies of UV-induced chromosomal aberrations, sister-chromatid exchanges and pyrimidine dimers in chicken embryonic fibroblasts. AB - Chicken embryonic fibroblasts, which possess photoreactivating enzyme were used to study the influence of photoreactivating light on the induction of pyrimidine dimers, sister-chromatid exchanges (SCEs) and chromosomal aberrations by 254 nm UV. While photoreactivation (PR) efficiently removed most of the induced dimers (75-95%), the frequencies of SCEs and chromosomal aberrations were reduced only by about 30-65%, in parallel experiments. Since pyrimidine dimers are the only photoreactivable photolesions known, the reduction in the frequencies of SCEs and chromosomal aberrations on PR has been interpreted as due to disappearance of pyrimidine dimers, implying that these lesions are the primary events responsible for the induction of the biological end points studied. The possible reasons for the lack of quantitative relationship between the frequencies of dimers and the frequencies of SCEs and chromosomal aberrations are discussed. PMID- 6244489 TI - Methyldopa inhibition of suppressor-lymphocyte function: a proposed cause of autoimmune hemolytic anemia. AB - To test the hypothesis that methyldopa induces red-cell autoantibodies by inhibiting the activity of suppressor lymphocytes, we studied its effect on several immune functions. Methyldopa inhibited T-lymphocyte suppression of IgG production by peripheral-blood mononuclear cells stimulated by poke-weed mitogens. This effect occurred in isolated T cells incubated with methyldopa and in T cells obtained from patients taking methyldopa. In addition, the drug caused a 30 to 80 per cent reduction in the proliferative response of peripheral-blood mononuclear cells to mitogens in vitro, and this reduction primarily involved the activation of T lymphocytes. Methyldopa also caused a persistent elevation of intracellular lymphocyte cyclic AMP in vitro and in vivo. We postulate that methyldopa alters the immune system by causing a persistent increase in lymphocyte cyclic AMP, which inhibits suppressor T-cell function. These effects may lead to unregulated autoantibody production by B cells in some patients. PMID- 6244490 TI - Atypical generalized zoster with lymphadenitis mimicking lymphoma. PMID- 6244491 TI - Case 44-1979: herpes simplex encephalitis. PMID- 6244492 TI - Drug therapy: antiviral agents (second of two parts). PMID- 6244493 TI - Abelson murine leukaemia virus protein is phosphorylated in vitro to form phosphotyrosine. AB - The Abelson murine leukaemia virus protein (P120) can become phosphorylated in vitro by [gamma-32P]ATP. The protein has been purified from cell membranes to the point that in specific conditions virtually all of the incorporated 32P is in P120. The reaction is stimulated by Mn2+ and Mg2+ but not Ca2+ and is very rapid even at 0 degrees C. The phosphate is linked to P120 at tyrosine, a linkage not previously reported for a phosphorylation reaction. Phosphorylation may be involved in the transforming activity of viruses that cause leukaemia as well as sarcomas. PMID- 6244494 TI - Lactogenic receptor regulation in hormone-stimulated steroidogenic cells. AB - Receptor sites for lactogenic hormones such as prolactin (PRL), human growth hormone (HGH), and placental lactogens, are widely distributed in mammalian tissues, including mammary glands, steroid-secreting cells of the adrenal, testis, and ovary, and target cells of steroid hormone action such as liver, prostrate, and kidney. Although the biological functions of lactogen binding sites remain uncertain, a relationship between prolactin and lipoprotein metabolism is implied by the occurrence of prolactin receptors in steroidogenic cells of the gonads and adrenal, and by the ability of prolactin to increase esterified cholesterol in the testis. Recently, loss of testicular prolactin receptors has been observed following elevation of circulating luteinising hormone (LH) concentrations by the gonadotropin releasing hormone (GnRH) and its agonist analogues. The hormone dependence of lactogen receptor sites in steroid secreting cells was further analysed in rat testis, ovary, and adrenal glands after treatment with the respective trophic hormones, gonadotropin and ACTH. In each of these tissues, rapid and transient loss of lactogen receptors was observed after trophic hormone stimulation. These findings indicate that increased turnover of lactogen receptors is an important component of the target cell response, and suggest that prolactin receptors might be involved in the transport of lipoprotein precursors for steroid biosynthesis. PMID- 6244495 TI - HLA-restricted T-cell recognition of Epstein-Barr virus-infected B cells. AB - In mice the cytotoxic T-cell response to several types of virus is influenced by genes within the major histocompatibility complex; in particular, genetic control is exercised at the effector cell level through a requirement that virus-specific cytotoxic T cells recognise viral antigens in association with H-2K and H=2D region gene products on the surface of infected cells. In man the restriction which the analogous HLA-A, -B and -C-region gene products might place on virus specific T-cell function is still in dispute. The earliest and most controversial evidence concerns the Epstein-Barr virus (EBV), a B lymphotropic agent which causes infectious mononucleosis (IM) and which induces an unusually vigorous T cell response; cytotoxic T cells from IM patients' blood were shown to be EBV specific yet, in contrast to mouse systems, apparently free of any obvious HLA restriction. Since then T-cell recognition of EBV-infected B cells has assumed particular significance as a model system for the study of cytotoxic T-cell function in man. This report describes the results of a new approach clearly indicating that HLA-A and -B region products do indeed have a role in this system. PMID- 6244496 TI - DNA sequence of human papovavirus BK. PMID- 6244497 TI - Potassium channels in nodal and internodal axonal membrane of mammalian myelinated fibres. AB - Horakova et al. were the first to observe that the phase of late outward current carried by potassium ions in frog and squid nerve is virtually absent in voltage clamped rat nodes of Ranvier. This observation has been recently confirmed by Chiu et al. in rabbit nodes of Ranvier, suggesting that the nodal membrane in the mammal generally has few if any potassium channels. The present voltage-clamp experiments show that large potassium currents can, however, be produced in normal rabbit nodes of Ranvier by acute treatment designed to loosen the myelin from the axonal membrane. From this we conclude that whereas potassium channels are absent in the mammalian nodal membrane, they are normally present in the internodal axonal membrane at least in the paranodal region. PMID- 6244498 TI - Tumour promoter uncouples beta-adrenergic receptor from adenyl cyclase in mouse epidermis. AB - Alterations in beta-adrenergic receptor number and function and in the hormonal responsiveness of adenylate cyclase have been observed in transformed cells, and tumours. Phorbol myristate acetate (PMA), a potent tumour promoter in mouse skin, induces a dramatic loss of epidermal responsiveness to catecholamines in vivo, although basal levels of cyclic AMP are not affected. In other work we have shown that PMA treatment does not alter the number or affinity of epidermal beta receptors, although accumulation of cyclic AMP in response to isoprenaline injection is sharply inhibited. Evidence is presented here that PMA exerts this effect by uncoupling epidermal beta-receptors from adenylate cyclase. PMID- 6244499 TI - Herpes simplex virus depresses antibody production by affecting T-cell function. AB - Many viruses enter lympho-reticular cells during pathogenesis and thereby induce immunosuppression, which is of practical importance in that it may be related to overall virulence. Immunosuppression may result from a selective infection, as viruses often show an affinity for different lymphocyte subpopulations: Epstein Barr virus, for example, infects only a small percentage of B cells. We reported previously that herpes simplex virus (HSV) type 1 suppressed the induction of an antibody response to diphtheria toxoid in cultures of human tonsil cells, and that this seemed to result from the infection of a small percentage of T lymphocytes. However, as fully infectious virus was used in these experiments, it had probably spread from cell to cell in the course of the culture, so complicating the interpretation of the results. Accordingly, we have now reinvestigated the mechanism of immunosuppression using temperature-sensitivity (ts) mutants which fail to complete their growth cycle in the conditions selected for antibody synthesis. In this study, mutants tsB, tsD and tsF, derived from HSV type 1 strain 17, and ts 9, derived from HSV type 2 HG 52, were used. The results suggest that the immunosuppression is due to the selective infection by the viruses of helper T cells. PMID- 6244500 TI - V-J joining of immunoglobulin kappa genes only occurs on one homologous chromosome. AB - In general, heterozygous animal cells express both alleles at a particular locus. The only exceptions are cells of XX genotype after inactivation of one X chromosome, and immunoglobulin-producing cells; in each case only one of the two alleles is expressed in differentiated cells and their progeny. This phenomenon, termed allelic exclusion, has been described for several mammalian species including man and mouse. It has been shown that the variable (V) and constant (C) region genes of immunoglobulins undergo a rearrangement during ontogeny. We wished to test whether allelic exclusion in B cells could be the consequence of V and C-region rearrangement on one of the two homologous chromosomes only. For that reason we chose to analyse the rearrangement of immunoglobulin light chain genes in normal B lymphocytes isolated on the fluorescence-activated cell sorter. We now present evidence that during normal B-lymphocyte differentiation V-C rearrangement occurs only on one chromosome. PMID- 6244501 TI - Inherited defect in a Na+, K-co-transport system in erythrocytes from essential hypertensive patients. AB - The Na+ and K+ electrochemical gradients across cell membranes are believed to be maintained by the action of a Na+, K+-pump. In human erythrocytes this pump exchanges internal Na+ for external K+ in approximately a 1.5 ratio. Thus, when Na+-loaded/K+-depleted erythrocytes are incubated in physiological conditions they tend to recover their original low Na+/high K+ content. Surprisingly, in erythrocytes from healthy donors the net Na+ extrusion/K+ influx ratio exceeds the 1.5 ratio predicted for Na+, K+-pump-mediated fluxes whereas it is similar to this value in erythrocytes from essential hypertensive patients and some of their descendants. We now report that this difference is due to the presence of a Na+, K+-co-transport system in normal erythrocytes which extrudes both internal Na+ and K+ and is functionally deficient in erythrocytes of essential hypertensive patients and some of their descendants. No difference in passive Na+ permeability could be detected between normotoensive and hypertensive subjects. PMID- 6244502 TI - Is phosphatidic acid a calcium ionophore under neurohumoral control? PMID- 6244503 TI - Opiate receptors influence vasopressin release from nerve terminals in rat neurohypophysis. AB - A previous report described the existence of substantial amounts of enkephalin immunoreactivity and the occurrence of nerve terminals containing an enkephalin like material in the pars nervosa of rat pituitary. It was suggested that an enkephalin innervation of the pars nervosa originating from the magnocellular hypothalamic nuclei might regulate the secretion of neurohypophyseal hormones. The results of the present studies support this hypothesis, as we find that a stable enkephalin analogue (D-Ala 2,D-Leu5-enkephalin) inhibits the calcium dependent release of vasopressin evoked by electrical stimulation of the rat pituitary stalk in vitro. A similar inhibition of the stimulus-evoked vasopressin release is caused by morphine and beta-endorphin, and the inhibitory effects of the enkephalin analogue can be reversed by naloxone. These findings suggest the possible existence of inhibitory opiate receptors on the terminals of vasopressin fibres in the pars nervosa. PMID- 6244504 TI - Multiple opiate receptor sites on primary afferent fibres. PMID- 6244505 TI - Glycocalyx is not required for show inward calcium current in isolated rat heart myocytes. AB - The importance of the slow inward calcium current (Isi) in the excitation contration coupling process of cardiac muscle is well documented. The current can be attributed mainly to a calcium translocation from the extracellular space into the cell or a subsarcolemmal compartment of it. Isi has been suggested to have its source in and to be controlled by the surface coat of the sarcolemma (glycocalyx). The glycocalyx is destroyed in myocytes dissociated from adult heart tissue with solutions containing low calcium, collagenase and hyaluronidase (Fig. 1). By comparing the Isi data obtained in isolated myocytes with those reported for trabeculae or papillary muscles, we have now obtained evidence suggesting that the glycocalyx is not important in the genesis of Isi. PMID- 6244506 TI - Partial nucleotide sequence of the 300-nucleotide interspersed repeated human DNA sequences. PMID- 6244507 TI - Long spacers among ribosomal genes of Drosophila melanogaster. AB - The fruit fly, Drosophila melanogaster, has 200 tandemly arranged copies of the ribosomal RNA genes (rDNA) per haploid genome. One such cluster of rRNA genes occurs on the X and one on the Y chromosome. The basic repeating unit of the rRNA gene consists of a segment coding for 18S rRNA and 28S rRNA followed by a non transcribed spacer (Fig.1). In the X chromosome, there are two major size classes (12 and 17 kilobases) and numerous minor size classes of rDNA repeats. Most of this length heterogeneity is generated by insertions at a specific site in the 28S gene. The frequency and size patterns of these insertions in the 28S gene differ in the X and Y chromosomes. Electron microscopic analysis of rDNA-rRNA hybrids has shown that there is also length heterogeneity in the rDNA non transcribed spacer. This heterogeneity is due in part to internal sequence repetition. We have now examined further the length heterogeneity of the rDNA spacer and have observed a class of spacers that we shall refer to as 'long spacers'. The size and frequency of these long spacers are different in the X and Y rDNA. PMID- 6244508 TI - Nursing assessment in follow-up care of the renal transplant recipient. PMID- 6244509 TI - [Intraneoplastic local injection of adriamycin for malignant brain tumor chemotherapy--a clinicopathological study (author's transl)]. PMID- 6244510 TI - Effects of nigral and cortical stimulation on cyclic AMP in the caudate nucleus of the cat. PMID- 6244511 TI - Effects of substantia nigra stimulation on suralis-evoked spinal reflex activity: comparison with the effects of morphine and stimulation in the periaqueductal gray matter. PMID- 6244512 TI - The involvement of central alpha-adrenergic and histamine H2-receptors in the hypothermia induced by clonidine in the rat. PMID- 6244513 TI - Behavioral and neurochemical effects of repeated administration of delta 9 tetrahydrocannabinol in rats. PMID- 6244514 TI - Interaction of phencyclidine with drugs affecting cholinergic neurotransmission. PMID- 6244515 TI - Head twitches induced by LSD and quipazine: similarities and differences. PMID- 6244517 TI - [Alveolar carcinoma of the lung. Anatomo-clinical considerations and presentation of 4 cases]. AB - Alveolar carcinoma of the lung is a rare form that is often discovered casually, and may well be asymptomatic. Four personal cases are presented. The view is advanced that this is a distinct form that is clearly distinguishable from bronchogenic adenocarcinoma. It has a single site and is derived from the type II pneumocyte. Particular attention is given to the clinical and diagnostic features of alveolar carcinoma. It is felt that early diagnosis followed by radical surgery leads to a marked improvement in prognosis. PMID- 6244516 TI - Experimental gliomas: an autoradiographic study of the endothelial component. AB - Autochthonous gliomas were induced in rats by intracerebral inoculation of avian of avian sarcoma virus and studied by 3H-thymidine autoradiography. Parenchymal glial tumor cells had a 3H-labeling index (LI) of 3.0 to 13.6%. Endothelial cells in tumor blood vessels had an LI of 2.6 to 34.3%, independent of and in most instances higher than the LI of the glial tumor. Endothelial cells of normal blood vessels had an average LI of 0.3%. This study documents the high proliferative rate of the endothelial cells in anaplastic experimental gliomas, and emphasizes the necessity for seeking direct, incontrovertible evidence to determine whether or not the rapidly proliferating endothelial cells are malignant. PMID- 6244518 TI - [2 cases of carotid paraganglioma]. PMID- 6244520 TI - [Neoplasms of the right colon, of the right half of the transverse colon and multiple tumors of the large intestines]. PMID- 6244519 TI - [Tumors of the large intestine. Statistical research and histopathological findings]. PMID- 6244521 TI - Opioid peptides: endorphins and enkephalins. PMID- 6244522 TI - Maternal and neonatal infection with coxsackievirus. AB - Evidence is growing that relates maternal coxsackievirus infection to increased neonatal mortality and an increase of congenital anomalies. Four cases of fulminant perinatal coxsackievirus infections that were fatal to the newborns are presented. Coxsackievirus infections in pregnancy are usually either subclinical or produce minimal symptoms in the mother. The cases presented point out the potential severity of coxsackievirus infections in the neonatal period. Prevention of the disease and isolation of infected individuals are the mainstays of therapy. PMID- 6244523 TI - Herpes simplex in the amniotic fluid of an unaffected fetus. AB - A woman with a 7-year history of herpes progenitalis was delivered by cesarean section after herpes simplex virus was isolated from the cervix 2 weeks prior to delivery. No overt signs of herpes progenitalis had been observed during this pregnancy. At amniocentesis done the day of delivery to assess fetal maturity, herpes simplex virus was isolated from the amniotic fluid. An unaffected infant was delivered; she remains healthy at 18 months of age. Immunoglobulin levels in fetal serum and amniotic fluid did not indicate fetal infection. PMID- 6244525 TI - Evaluation of 10-0 polyglycolic acid and polyglactin suture in rabbit limbal wounds. AB - Sutures of 10-0 polyglycolic acid (Dexon) or polyglactin (Vicryl) were used to close limbal incision in rabbits. When seven Dexon or Vicryl sutures were used alone wound disruption occurred in eight of twelve eyes. Sutures disappeared at 4 5 weeks. When three 10-0 nylon sutures were alternated with four 10-0 absorbable sutures, wound integrity was greatly improved. The handling properties of these sutures were excellent and inflammatory reactions were minimal. The 10-0 Dexon and Vicryl did not appear to differ in their properties, but they were insufficient for lasting would closure when used alone. It is suggested that these sutures not be used as the sole closure for limbal wounds. PMID- 6244524 TI - An antitumor antibody in normal human serum: reaction of anti-T with breast carcinoma cells. AB - Carcinoma of the breast is now the most common malignant disease of females in Europe and North America. The most critical single factor in determining the success or failure of treatment is the extent of the disease at diagnosis. A sensitive immunoperoxidase technique was utilized to (1) detect the presence in normal human serum of antibody directed against breast carcinoma cells (anti-T antibody), and (2) determine whether this antibody could be used to discriminate between benign and malignant breast epithelium in sections of formalin-fixed, paraffin-embedded tissue. A total of 11 benign and 11 malignant breast lesions were examined for evidence of binding of human immunoglobulin, before and after application of purified anti-T antibody or normal human AB serum (containing anti T antibody). Malignant cells showed significant binding of human immunoglobulin (anti-T); benign or normal cells did not. Clear immunohistological separation of benign and malignant breast lesions appears to be potentially feasible by this method. PMID- 6244526 TI - Pigmented neuroectodermal tumor of infancy. An example of rarely expressed malignant behavior. AB - A 4-month-old patient presented with a melanotic neuroectodermal tumor. The tumor continued to progress and recur following each surgical intervention and the patient died at the age of 38 months, 36 months following discovery of the tumor. This article describes the clinical and pathologic features of the disease. At autopsy, the tumor resembled that of a neuroblastoma. PMID- 6244527 TI - Immune competence of newborn lymphocytes. PMID- 6244528 TI - American Academy of Pediatrics. Committee on Drugs. Marijuana. PMID- 6244529 TI - [Side effects of glucoccorticoid therapy in children and the methods of their prevention]. PMID- 6244530 TI - [Thyrotropic reserve in Sheehan's syndrome. Study in 36 patients (author's transl)]. AB - Thyrotropic involvement is considered to be constant in Sheehan's syndrome. In this study, plasma thyroid stimulating hormone (TSH) levels were similar to those of normal women (respectively: 1.01 +/- 0.54 ng/ml and 0.54 +/- 0.27 ng/ml). The pituitary response to the administration of TRH was nul in 63.8% of cases. In one patient, thyrotrophic function was normal. Twelve patients had a minimal or moderate reserve of TRH. By order of prevalence, thyrotrophic involvement succeeds that of the somatotrophic and lactotrophic axes. There is no correlation with involvement of other axes which would make it possible to define a sequential course of pituitary lesions. These results are discussed in the light of the existing literature. The TRH test does not offer certain evidence of hypothalamic involvement. PMID- 6244531 TI - [Primary liver cancer in a woman taking oral contraceptives]. PMID- 6244532 TI - [Inhibition of the renin-angiotensin system: a major breakthrough in the treatment of arterial hypertension?]. PMID- 6244533 TI - Hospitals should do the sick no harm. 2. Why are bacteria harmful? PMID- 6244534 TI - Emotional aspects of mastectomy: planning a caring programme. PMID- 6244535 TI - [Characteristics of adenohypophseal secretory activity in children with thymomegaly]. AB - The radioimmunological method was applied in the study of ACTH, STH, and prolactin content in thymomegaly combined with pneumonia, and in practically healthy children. A comparative analysis of hormonal parameters depending on the functional condition of the thymus demonstrated a directly proportional correlation between the STH, prolactin level, and the thymus hyperplasia; there proved to be a reverse relationship between the ACTH level and thymomegaly. Hypoadrenocorticotropinemia, hypersomatotropinemia, and hyperprolactinemia could be used as diagnostic criteria in thymomegaly. PMID- 6244536 TI - [Interrelationships of melatonin and other hormones and biogenic amines]. PMID- 6244537 TI - Double-stranded RNA inhibits a phosphoprotein phosphatase present in interferon treated cells. AB - In accord with previous studies, (I)n . (C)n, a potent inhibitor of the cell-free protein-synthesizing system of interferon-treated L cells, stimulates incorporation of 32P from [gamma-32P]ATP into the 67,000-dalton protein, P1. The double-stranded RNA (I)n . (br5C)n, which is inactive as an inhibitory of protein synthesis, does not stimulate phosphorylation of P1 under conditions approximating those of protein synthesis. However, we have found conditions under which (I)n . (br5C)n is approximately as effective as (I)n . (C)n in stimulating incorporation of label from [gamma-32P]ATP into 67,000-dalton protein. Upon transfer of labeled P1 from these conditions to those compatible with protein synthesis, there is a time-dependent decrease in label in the 67,000-dalton protein. This decrease is more rapid in the presence of (I)n . (br5C)n than in the presence of (I)n . (C)n. This differential decrease is also observed when 32P labeled extracts are diluted into buffer containing 10 mM ATP, hexokinase and 1 and M glucose, or Escherichia coli alkaline phosphatase. A partial proteolytic digest of P1 labeled in the absence of double-stranded RNA or in the presence of (I)n . (C)n or (I)n . (br5C)n gives rise to similar peptide patterns. These results suggest that dephosphorylation as well as phosphorylation determines the net incorporation of 32P into P1. Moreover, these results suggest the existence of a phosphatase activity that may be inhibited more strongly by (I)n . (C)n than by (I)n . (br5C)n. PMID- 6244538 TI - Mitochondrial membrane biogenesis: identification of a precursor to yeast cytochrome c oxidase subunit II, an integral polypeptide. AB - Many of the polypeptides made on endogenous ribosomes inside of yeast mitochondria are hydrophobic "integral polypeptides" which are subunits of at least three oligomeric enzyme complexes (cytochrome c oxidase, rutamycin sensitive ATPase, and coenzyme QH2-cytochrome c reductase) of the inner mitochondrial membrane. In order to elucidate the pathway(s) followed by these polypeptides into the inner membrane we have used an in vitro mitochondrial translation system from yeast. By inhibiting this system with aurintricarboxylic acid, we have been able to demonstrate and accumulate a transient precursor to subunit II of cytochrome c oxidase. This precursor, designated II', is approximately 1,500 daltons larger than mature subunit II and most likely is a form of subunit II with an NH2-terminal extension. Although this precursor appears to be processed cotranslationally under normal conditions, it does associate in unprocessed form with mitochondrial membranes when allowed to accumulate in the presence of aurintricarboxylic acid, and it can be processed postranslationally upon removal of the drug. None of the other mitochondrial translation products made in this system exhibits larger precursors. These results indicate that at least one mitochondrial translation product has a transient "leader sequence" a,d is inserted into the inner mitochondrial membrane and processed cotranslationally, but they suggest that other pathways may be followed by the other translation products. PMID- 6244539 TI - Properties of a copper-containing cytochrome c1aa3 complex: a terminal oxidase of the extreme thermophile Thermus thermophilus HB8. AB - From the plasma membrane of Thermus thermophilus HB8 we have partially purified a detergent-solubilized complex of cytochromes a and c1 that actively catalyzes the transfer of electrons from ascorbate via a redox dye to oxygen. The complex is composed of two types of polypeptides, with molecular weights of approximately 55,000 and 33,000. Quantitative analysis revealed the presence of heme a, heme c, and copper in a ratio of 2:1:2, with the heme a being present at 10 +/- 1.3 nmol/mg of protein. The heme c was shown to be associated with the molecular weight 33,000 peptide and is suggested to be of the c1 type. The optical and electron paramagnetic resonance properties of this complex were found to be similar to those of eukaryotic cytochrome oxidase, suggesting the following arrangement of chromophores: a magnetically isolated cytochrome c1 and an oxygen reducing functional unit consisting of two heme a groups and two copper ions associated with one or more larger peptides. PMID- 6244541 TI - Origin of replication of the DNA of a herpesvirus (pseudorabies). AB - During the first round of the replication of pseudorabies virus DNA, replicating DNA is mainly in the form of circles. The main origin of replication is located inthe region of the molecule bearing the inverted repeat. Replication proceeds unidirectionally from the origin. PMID- 6244540 TI - Reovirus-induced modification of cap-dependent translation in infected L cells. AB - The translational apparatus in cell-free extracts prepared from L cells infected with reovirus undergoes a time-dependent transition from cap dependence to cap independence. Extracts from uninfected L cells translate capped reovirus mRNA at high efficiency and synthesize the expected three size classes of reovirus polypeptides, and the translation is sensitive to m7G(5')ppp. This same extract translates uncapped mRNA at a much lower efficiency. In contrast, extracts from infected L cells translate uncapped reovirus mRNA at high efficiency and synthesize the correct three size classes of polypeptides, and the translation is not sensitive to inhibition by m7G(5')ppp. Infected cell extracts translate capped mRNA at reduced efficiency (a,proximately 25%), the translation is not sensitive to inhibition by m7G(5')ppp, and the correct three size classes of viral polypeptides are not synthesized. These observations may explain how reovirus takes over the host translational apparatus. PMID- 6244542 TI - Unusual features in the nucleotide sequence of a cDNA clone derived from the common region of avian sarcoma virus messenger RNA. AB - We have constructed a recombinant plasmid containing a 700-base pair (bp) cDNA copy of the common region present at the 3' end of Schmidt-Ruppin avian sarcoma virus (ASV) 21S mRNA. The cDNA was inserted into plasmid pBR322 at the Pst I site by the G-C tailing method. A restriction map of the cloned insert from a recombinant plasmid pSRI indicates that it corresponds to the 3' end of the ASV genome. R-loop analysis with ASV genomic RNA indicates that the insert is colinear with the ASV genome over most of its length. The sequence of 331 bp at the 3' end of the DNA insert was determined and shows that the insert contains extra sequences not found at the 3' end of ASV genomic RNA. Following the terminally redundant sequence of 20 bp that has been found at the extreme 3' end of genomic RNA is a sequence of 79 bp that is almost identical to that located immediately next to the 20-bp repeat at the 5' end of ASV genomic RNA. This is followed by 18 bp of unique sequence, possibly of host origin. The structure of the clone suggests that ASV mRNA may differ from genomic RNA at its 3' end and that 21S mRNA is transcribed from integrated ASV DNA and contains at its 3' end sequences derived both from the 5' end of the ASV genome and from host DNA adjacent to the site of integration. The presence of termination codons in all three reading frames suggests that the common region probably does not contain coding sequences. However, the presence of sequences that resemble probable promoter sites supports the possibility that this region may be involved in the regulation of transcription. PMID- 6244543 TI - A two-subunit cytochrome c oxidase (cytochrome aa3) from Paracoccus dentrificans. AB - Cytochrome c oxidase (ferrocytochrome c: oxygen oxidoreductase, EC 1.9.3.1) was purified from the cytoplasmic membrane of the bacterium Paracoccus denitrificans. The enzyme contains two heme groups (a and a3) and two copper atoms per minimal unit, oxidizes mammalian cytochrome c at a high rate, and, when incorporated into liposomes, generates an electrochemical proton gradient during cytochrome c oxidation. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis reveals only two subunits of apparent molecular weights 45,000 and 28,000; they appear to correspond to the two largest mitochondrially made subunits of the seven-subunit cytochrome c oxidase isolated from yeast mitochondria. Because of its structural simplicity. Paracoccus cytochrome c oxidase offers new possibilities for exploring the mechanism of cytochrome c oxidase function. PMID- 6244544 TI - Cloning DNA sequences from influenza viral RNA segments. AB - DNA sequences corresponding to gene segments that code for the nonstructural protein, the matrix protein, and the hemagglutinin of influenza A virus [strain A/Udorn/72 (H3N2)] were cloned in Escherichia coli pBR 322. Initially, positive and negative cDNA strands were prepared separately by reverse transcription. The positive strands of cDNA were transcribed from genomic RNA segments by using a specific dodecamer DNA sequence as a primer; the negative strands of cDNA were transcribed from cytoplasmic viral mRNA segments by using an oligo(dT) primer. DNA duplexes corresponding in size to the virus RNA segments were then purified, inserted into the plasmid DNA, and used for transformation of E. coli. The influenza virus-specific DNA sequences isolated from recombinant plasmid molecules were characterized by mapping restriction enzyme cleavage sites. In addition, the orientation of cloned DNA was determined with reference to the 3' terminus of viral RNA. PMID- 6244545 TI - Differential affinities of simian virus 40 large tumor antigen for DNA. AB - The binding of simian virus 40 (SV40) large tumor antigen (T antigen) to DNA was analyzed by using the salt-sensitive affinities of the protein for various DNAs immobilized on cellulose. At least two types of interactions could be distinguished that differed in their stability. Higher salt concentrations were required to elute T antigen from SV40 DNA than from calf thymus DNA; and even greater salt concentrations were required for the lution of T antigen from multiorigin SV 40 DNA compared to wild-type SV40 DNA. This would indicate that T antigen can bind weakly or strongly to DNA, depending on the DNA sequence. It was also found that a greater proportion of rapidly labeled or newly synthesized T antigen binds more efficiently and tightly to multiorigin SV40 DNA than to long labeled or older forms of T antigen. This approach can be utilized not only to distinguish between different forms of T antigens which vary in their affinities for DNA but also for rapidly obtaining highly enriched T antigen preparations. PMID- 6244546 TI - Isolation and characterization of beta-endorphin-like peptides from bovine brains. AB - Four beta-endorphin-like peptides from bovine brain extracts have been identified by their behavior in CM-cellulose chromatography, gel filtration, high performance liquid chromatography, and radioimmunoassay. Two of them have been isolated in sufficient quantity for amino acid analysis, radioimmunoassay, and radioreceptor assay. One peptide has an amino acid composition nearly identical to that of beta-endorphin with 56% of the radioimmunoreactivity and 2.3% of the potency in the radioreceptor assay of beta-endorphin. The amino acid content of the other beta-endorphin-like peptide is very different from that of bovine beta endorphin but it has 47% of the radioimmunoreactivity and 1% of the potency in the radioreceptor assay of beta-endorphin. PMID- 6244547 TI - Reassembly of protein-lipid complexes into large bilayer vesicles: perspectives for membrane reconstitution. AB - Protein-lipid complexes in apolar solvents reassemble into large bilayer protein lipid vesicles (PLVs) with diameters of several micrometers. PLVs form spontaneously upon hydration of the protein-lipid complex residue after solvent removal. This procedure has been applied to the following membrane proteins: bovine and squid rhodopsin, reaction centers from Rhodopseudomonas sphaeroides, beef heart cytochrome c oxidase, and acetylcholine receptors from Torpedo californica. PLVs have a large internal aqueous space (e.g., 790 mul/mg of lipid for cattle rhodopsin vesicles). Freeze-fracture replicas of PLVs revealed that both internal and external leaflets contained numerous intramembranous particles with diameters between 80 and 120 A, depending on the specific protein incorporated in the membrane. The optical spectral properties of rhodopsin and reaction centers in PLVs were similar to those recorded in the respective natural membrane. Furthermore, bovine rhodopsin in PLVs was chemically regenerable with 9 cis-retinal. Actinic illumination induced proton efflux from reaction center vesicles that was abolished by proton ionophores. Therefore, this method is suitable for the incorporation of some membrane proteins in their functional state. PLVs were penetrated with microelectrodes and visualized by the injection of a fluorescent dye. Preliminary electrical recordings were obtained by sealing PLVs to a hole in a septum separating two aqueous compartments. These studies suggest that PLVs assembled by this procedure permit the simultaneous analysis of reconstituted membranes by chemical, optical, and electrical techniques. PMID- 6244548 TI - Methylation of integrated adenovirus type 12 DNA sequences in transformed cells is inversely correlated with viral gene expression. AB - The adenovirus type 12 (Ad12) DNA sequences integrated into the DNA of four lines of Ad12-transformed hamster cells are extensively methylated. Methylation in mammalian cell DNA is believed to occur predominantly at 5'-C-G-3' sequences. The majority, although not all, of the 5'-C-C-G-G-3' sequences present in integrated Ad12 DNA are methylated. Ad12 DNA isolated from purified virions, on the other hand, is not methylated to any significant extent. The segments of the integrated viral DNA comprising early genes, which are expressed as mRNA in two lines of Ad2 transformed hamster cells, are undermethylated in comparison to late viral segments, which are not expressed and are extensively methylated. In contrast, in two lines of Ad12-induced rat brain tumor cells, some of the late viral genes have been shown to be expressed as mRNA. The segment of the integrated Ad12 DNA that comprises these late genes, the EcoRI B fragment, is undermethylated in comparison to the extensive methylation of the same fragment in Ad12-transformed hamster cells. Thus, there appears to exist a striking inverse correlation between the levels of methylation of specific DNA segments and the extent to which these segments are expressed as mRNA. The functional significance of this correlation remains to be determined. It may provide a clue to understanding the regulation of gene expression in transformed cells and perhaps in eukaryotic cells in general. PMID- 6244549 TI - Isolation of a replication origin complex from Escherichia coli. AB - A complex consisting of replicative origin DNA and several proteins was isolated from Escherichia coli. Cells of temperature-sensitive mutants were labeled at the origin and fractionated by sucrose gradient centrifugation. A complex highly purified in origin DNA sedimented as a unique band. This complex dissociated at high concentration, above 0.2 M KCl. Upon dialysis, the complex reformed, allowing further purification of its constituents. Three major protein bands were found, corresponding to proteins of the outer membrane. The complex did not sediment with membrane fractions, but adhered to the outer membrane in the presence of magnesium. PMID- 6244550 TI - Charge selectivity at the lipid-protein interface of membranous Na,K-ATPase. AB - Lipid interactions with the integral membrane protein Na,K-ATPase (ATP phosphohydrolase, EC 3.6.1.3) purified from the electric organ of Electrophorus electricus were studied by spin labeling. A protein-associated component (boundary layer) in equilibrium with the fluid bilayer is clearly evident in the electron spin resonance spectra. The influence of charge on this equilibrium was determined by varying the head group of the lipid while maintaining the chain length and the position of the label constant. The lipid spin labels were 14 proxylstearylmethyl phosphate and the corresponding dimethylphosphate, alcohol, and quaternary amine. By using a pairwise spectral analysis, as well as a conventional spectral analysis, the binding affinity was found to decrease in the order of negative greater than neutral greater than positive charges. The fraction bound decreased from about 0.57 for the negatively charged phosphate to 0.25 for the positively charged quaternary amine. The amount of each bound lipid was nearly constant over the temperature range investigated (5-35 degrees C). High salt concentrations reversibly abolished the selectivity between the labels, confirming the role of charge in the binding equilibria. PMID- 6244551 TI - Selective protection of stereospecific enkephalin and opiate binding against inactivation by N-ethylmaleimide: evidence for two classes of opiate receptors. AB - Stereospecific binding of 3H-labeled [D-Ala2,D-Leu5]enkephalin is irreversibly inactivated by the sulfhydryl group alkylating agent N-ethylmaleimide. This inactivation, like that of opiate binding, exhibits pseudo-first-order kinetics with a half-inactivation time of 10-12 min. The presence of opiates or enkephalins during incubation with N-ethylmaleimide provides good protection. Ouantitative studies of protection demonstrate that naltrexone and morphine are 20 and 8 times, respectively, more effective in protecting the binding of [3H]naltrexone than that of [3H]enkephalin. [D-Ala2,Leu]Enkephalin and [D Ala2,Met]enkephalin, however, are more effective (7 and 30 times, respectively) for the protection of 3H-labeled [D-Ala2,D-Leu5]enkephalin binding. These results provide strong evidence for the existence of two classes of opiate receptor in rat brain. PMID- 6244552 TI - In vitro synthesis of the full-length complement of the negative-strand genome RNA of vesicular stomatitis virus. AB - Under the normal conditions of in vitro RNA synthesis, the virion-associated RNA polymerase of vesicular stomatitis virus synthesizes five monocristronic mRNAs and a 48-nucleotide-long leader RNA that represents the exact 3'-terminal region of the genome RNA [Colonno, R. J. & Banerjee, A. K. (1978) Cell, 15, 93-101]. When the transcribing core was preincubated with ATP and CTP, reisolated, and then incubated in the presence of the beta, gamma imido analogue of ATP (AdoPP[NH]P) and the three normal ribonucleoside triphosphates, the full-length complementary strand of the genome RNA was synthesized in vitro. The results suggest that specific phosphorylated states of regulatory proteins may control transcription in vitro to generate the full-length plus strands. PMID- 6244553 TI - Sequence of picornavirus RNAs containing a radioiodinated 5'-linked peptide reveals a conserved 5' sequence. AB - Virion RNA (vRNA) from poliovirus type 1 (PV1), poliovirus type 2 (PV2), and coxsackie virus B1 (Cox B1) were treated with proteinase K to remove all but a small peptide of the covalently attached 5' genome-linked virion protein (VPg). The peptide on these RNA molecules was then treated with Bolton-Hunter 125I reagent, which iodinates primary amine groups, in order to obtain specific 5' terminal radioactive labeling. Sequences of 125I-labeled vRNAs were determined by using a set of base-specific RNases and a partial alkaline hydrolysis "ladder." The first 20 positions of these RNAs show a remarkable conservation of sequence. The initial 10 nucleotides are identical in PV1, PV2, and Cox B1, with the sequence VPg-pU-U-A-A-A-A-C-A-G-C. The next 10 nucleotides show a one-base difference between PV1 and PV2 and 50% homology between PV1 and Cox B1. This conserved 5' region may provide a recognition site for interaction between the viral mRNA and the host translation system. PMID- 6244554 TI - Organization of the recA gene of Escherichia coli. AB - The restriction map of a BamHI DNA fragment that contains the recA gene of Escherichia coli has been established and a large portion of the fragment's nucleotide sequence has been determined. The coding region of the recA gene contains 1059 nucleotide residues and encodes a single protein of 353 amino acid residues. The amino acid sequence of the first five residues of the NH2 terminus of the recA protein agrees with the sequence predicted from the DNA sequence except for the absence of formylmethionine in the purified protein. Immediately after the coding sequence, there is a G+C-rich sequence with dyad symmetry followed by an A+T-rich sequence. These could signal termination of transcription. The site of initiation for synthesis in vitro of the recA messenger RNA has been determined by analysis of the 5' nucleotide sequence of [gamma-32P]ATP-labeled transcripts. The promoter region shos a high degree of symmetry and contains sequences commonly found in recognition and binding sites for RNA polymerase. PMID- 6244555 TI - Alternative method for identifying reconstituted cells. AB - Enucleation techniques combining mild centrifugation in the presence of cytochalasin B permit cells to be separated into nuclear fragments (karyoplasts) and cytoplasmic fragments (cytoplasts). These fragments, though stable for a short time, will ultimately degenerate by the procedures described in this report. One can, however, fuse cytoplasts to karyoplasts by using polyethylene glycol and obtain viable reconstituted cells whose properties may be useful for understanding some aspects of the nuclear-cytoplasmic interactions associated with tumorigenicity and steroidogenesis. However, the presence of cybrids, hybrids, and parental whole cell contaminants along with the reconstituted cell population make it necessary to have genetic markers that reside in both the nucleus and cytoplasm in order to preferentially identify reconstituted cells derived from a karyoplast fused to a cytoplast. By utilizing the Y-1 cell line, which is tumorigenic and responds to corticotropin by secreting steroids, and the AMT-BU-A1 (AMT) cell line, which is nontumorigenic and does not respond to corticotropin but has a nuclear marker, BrdUrd(r), and a cytoplasmic marker, CAP(r), we have reconstituted cells containing Y-1 karyoplasts and AMT cytoplasts. In this report we extend our previous techniques by describing an identification procedure that allowed us to isolate cells reconstituted from AMT karyoplasts fused to Y-1 cytoplasts. The results of these experiments support the concept that with these cell lines the nucleus (karyoplast) is ultimately sufficient to control the phenotypic expression or suppression of tumorigenicity and steroidogenesis. PMID- 6244556 TI - Target cell specificity of defective avian leukemia viruses: hematopoietic target cells for a given virus type can be infected but not transformed by strains of a different type. AB - Defective avian leukemia viruses of the avian erythroblastosis (AEV), avian myelocytomatosis (MC29), and avian myeloblastosis (AMV) type induce the proliferation of leukemic cells with properties of erythroblasts, macrophages, and myeloblasts, respectively. Their target cells can be separated and have properties of cells of the erythroid (AEV) and myeloid lineage (MC29 and AMV), respectively. In the present study we have shown that this target cell specificity is not due to the ability of the different strains to infect only certain types of hematopoietic cells. Instead, AEV was found to replicate in macrophages and to induce the expression of p75 AEV, its presumptive transforming protein. Likewise, MC29 was found to replicate in AEV-infected erythroblasts as well as in AMV-infected myeloblasts and to express the p110 MC29 protein in these cells. Superinfection with MC29 or AMV of ts34 AEV-infected erythroblasts did not impair their capacity to accumulate hemoglobin after shift to nonpermissive temperature. Our results support a model in which the transforming proteins of AEV, MC29, and MAV block the differentiation of their target cells by competitively inhibiting the action of a hypothetical homologous cellular differentiation protein synthesized in the corresponding target cells only. PMID- 6244557 TI - Epidermal growth factor and expression of specific genes: effects on cultured rat pituitary cells are dissociable from the mitogenic response. AB - Cultured rat pituitary tumor cells, GH3/D6, which synthesize both growth hormone and prolactin, have cell-surface epidermal growth factor (EGF) receptor sites (34,000 per cell) that bind 125I-labeled EGF with a high affinity (Kd approximately 1 nM). Prolonged treatment of the cells with EGF did not stimulate cell division but did inhibit thyroid hormone-stimulated cell growth. In addition, EGF altered the morphology of the cells from a rounded to an elongated conformation. EGF also induced a perturbation of chromatin structure in GH3 cell nuclei that was detected by an increase (40%) in the number of rifampicin resistant initiation sites for bacterial RNA polymerase. This was accompanied by an increased synthesis of prolactin and an inhibition of synthesis of growth hormone. In the presence of EGF, the synthesis of growth hormone was no longer inducible by thyroid hormone, but it remained responsive to glucocorticoids. The results demonstrate that EGF can elicit major effects on the cellular phenotype and expression of specific genes in the absence of a proliferative response. This suggests that EGF can also regulate differentiated cellular functions. PMID- 6244558 TI - Expression of Epstein-Barr virus genes in different cell types after microinjection of viral DNA. AB - Gene expression of Epstein-Barr virus (EBV) was studied after microinjection of viral DNA into different types of cells. Raji TK- cells, known to express viral gene functions after superinfection with the EBV-P3HR-1 virus strain, were attached to plastic dishes by using anti-lymphocyte IgG, phytohemagglutinin, or concanavalin A as a ligand. It was difficult to inject DNA into the small and fragile Raji cells. After formation of polykaryons by cell fusion, microinjection became more efficient. At 24 hr after injection of P3HR-1 virus DNA, 90-100% of the injected cells expressed the early antigen complex as observed by immunofluorescence staining; 70-80% of the cells simultaneously incorported [3H]thymidine, indicating that thymidine kinase is expressed after injection of viral DNA. Additionally, synthesis of the virus capsid antigen was demonstrated in 20-30% of the recipient Raji cells. Human diploid fibroblasts, African green monkey kidney cells, and rat fibroblasts, which do not represent natural target cells for EBV, could also be induced to synthesis of early antigen complex by injection of P3HR-1 virus DNA. PMID- 6244559 TI - Coupling of active ion transport and aerobic respiratory rate in isolated renal tubules. AB - We report the results of studies in which the cytoplasmic coupling between Na+,K+ ATPase activity (presumably a measure of active transport) and the mitochondrial respiratory rate was investigated in a tubule suspension from the rabbit kidney cortex. Simultaneous measurements of the redox state of mitochondrial nicotinamide adenine dinucleotide (NAD) (performed fluorometrically), the cellular ATP and ADP concentrations, and the oxygen consumption rate (QO2) were made under conditions known to alter the Na+,K+-ATPase turnover. Ouabain (25 microM) caused: (i) a 54% inhibition of QO2, (ii) a net reduction of NAD, and (iii) a 30% increase in the ATP/ADP ratio. The addition of K+ (5 ?M) to K+ depleted tubules caused: (i) an initial 127% stimulation of QO2 followed by a new steady-state QO2 50% above control, (ii) an initial large oxidation of NAD followed by a new steady state more oxidized than the control level, and (iii) a 47% decrease in the cellular ATP/ADP ratio. These data indicate that the cellular ATP and ADP concentrations or the ATP/ADP ratio may be part of the coupling mechanism linking Na+,K+-ATPase turnover and the aerobic metabolic rate in kidney. PMID- 6244560 TI - Kinetics of decay in the expression of interferon-dependent mRNAs responsible for resistance to virus. AB - We used 5,6-dichloro-beta D-ribofuranosyl-benzimidazole (DRB), a selective and reversible inhibitor of mRNA production, to investigate the regulation of the pathway leading to resistance to viruses in cells treated with interferon (IF). DRB allows initiation of transcription but promotes premature termination of the nucleotide chains, so that it abolishes interferon-dependent protection against viruses. When the DRB is removed, synthesis of complete mRNAs can resume. Mouse L 929 cells were exposed to 100 microM DRB before and during a 1-hr pulse of IF followed by treatment with antibody to IF to prevent cell-to-cell spread of IF after that time. At different intervals thereafter the cells were washed and the DRB was replaced by medium; after further incubation, the cells were infected with vesicular stomatitis virus. Resistance to virus was inversely proportional to the duration of the block imposed by DRB. When the DRB was removed soon after the IF pulse, substantial protection from virus ensued, but none developed when removal of the DRB was deferred for 5-6 hr. Cells exposed to DRB for 5 hr, then pulsed with IF for 1 hr, still mounted a strong antiviral response. The data show that the ability of cells to resist viral infection decays within 5-6 hr after treatment with IF. Whether the decay is due to shutoff of transcription of mRNAs, or to their destruction or degradation, or whether regulation takes place at one or more subsequent steps in the antiviral pathway, remains to be determined. PMID- 6244561 TI - Growth and differentiation of embryonal carcinoma cell line F9 in defined media. AB - This paper reports the growth and differentiation of the mouse embryonal carcinoma cell line F9 in completely defined culture media. The defined growth medium, referred to as EM-3, contains plasma fibronectin, insulin, and transferrin in place of serum. F9 cells cultured in EM-3 for over 15 generations retain their ability to form tumors and to differentiate. Fibronectin is essential for the attachment of F9 cells in defined media and its effect can be blocked with affinity-purified anti-fibronectin. When retinoic acid was added to EM-3, the F9 cells differentiated. The majority of the the newly formed cells differed from patient F9 cell two major respects: (i) they were morphologically different; and (ii) they secreted plasminogen activator, and the secretion was stimulated by dibutyrlyl adenosine cyclic monophosphate. PMID- 6244562 TI - Suspension culture of separated follicles consisting of differentiated thyroid epithelial cells. AB - We have prepared thyroid follicles in suspension culture to use as a model system in vitro for investigation of some properties of the thyroid gland. The follicles were free of endothelial cells, fibroblasts, and other nonepithelial cells. They were prepared by collagenase treatment of minced rat thyroid glands followed by differential filtration of the suspension through nylon meshes. Small clusters of principal thyroid epithelial cells were separated from large fragments and single cells. They were cultured in dilute suspension in Coon's modified F-12 medium in dishes coated with agarose to avoid having the cells attach to the dishes. By culture day 3, most of the clusters formed closed follicles containing a periodic acid-Schiff-positive colloid but without a basal lamina. Follicle walls contained an occasional C cell. The epithelium resembled that in the thyroid of a recently hypophysectomized rat, with normal polarity and organelle complement normal with respect to position and abundance, with basally located lysosomes, no pseudopods, and no colloid droplets. The cells were responsive to thyroid-stimulating hormone (thyrotropin) and to dibutyryl cyclic AMP. Thyroid-stimulating hormone at 10 munits/ml resulted in apical migration of lysosomes and formation of pseudopods and colloid droplets within 30 min; longer exposure resulted in depletion of luminal colloid. The results indicate that the suspended follicles resemble follicles in vivo with respect to morphology and responsiveness to thyroid stimulating hormone in the absence of other cell types. PMID- 6244563 TI - Colchicine inhibits epidermal growth factor degradation in 3T3 cells. AB - Colchicine (2 microM) did not affect the initial rate of association of 125I labeled epidermal growth factor (125I-EGF) to Swiss 3T3 cells but continued incubation (up to 24 hr) led to an increase in cell-associated radioactivity. The effect is also produced by Colcemid, vinblastine, and podophyllotoxin but not by lumicolchicine. Disruption of microtubules with colchicine does not alter the rate of "down regulation" of EGF receptors, suggesting the binding and internalization of the factor proceed unchanged. However, colchicine markedly decreases the rate of appearance of acid-soluble radioactivity from cells either incubated continuously with 125I-EGF for 24 hr or exposed to the radioactive peptide for only 1 or 3 hr. The results indicate that colchicine decreases the rate of degradation of internalized 125I-EGF. Because antitubulin agents enhance the mitogenic effect of EGF our results suggest that peptide degradation can be dissociated from the long-term biological effect. PMID- 6244564 TI - Akvr-1, a dominant murine leukemia virus restriction gene, is polymorphic in leukemia-prone wild mice. AB - We describe a restriction gene (Akvr-1, for AKR virus restriction) that is polymorphic for two alleles, Akvr-1R (restrictive) and Akvr-1r (susceptible), in a feral population of mice (Mus) musculus domesticus) at a squab farm near Lake Casitas (LC) in southern California. Akvr-1k is a dominant allele that exhibits 100% penetrance in prevention of viremia of AKR endogenous retrovirus and of virus-mediated lymphoma in LC (Akvr-1RR) X AKR F1 hybrids. The restriction phenotype segregates as a single Mendelian locus in backcrosses to AKR mice. Akvr 1R likewise is effective in restriction of NB-tropic Moloney murine leukemia virus-induced viremia and NB-tropic Friend virus-induced splenomegaly but fails to restrict expression or pathogenesis of LC-derived amphotropic retrovirus. Pleiotropic restriction of AKR, Friend, and Moloney ecotropic viruses, but not of amphotropic virus, suggests that the viral targets of Akvr-1 in the three ecotropic viruses are similar to each other and distinct from the target in the LC-amphotropic virus. The relationship of Akvr-1 to previously reported murine restriction loci Fv-1, Fv-2, and Fv-4 is discussed. PMID- 6244565 TI - Mutant and recombinant avian retroviruses with extended host range. AB - Avian retroviruses of subgroups B and D efficiently infect chicken (C/E) but not turkey (T/BD) cells. We describe here three variants of subgroup B and D viruses that infect both cell types equally well. One of these viruses, NTRE-4, was a recombinant between transformation-defective Prague (Pr) strain Rous sarcoma virus (RSV) subgroup B and the endogenous virus RAV-0; the second, SR-DE-1, was a recombinant between Schmidt-Ruppin RSV subgroup D and defective endogenous virus information. T1 oligonucleotide fingerprint analysis of the genomes of these two viruses showed only a small alteration in the portion of the env gene responsible for subgroup specificity, as indicated by the presence of a single subgroup E oligonucleotide in an otherwise purely subgroup B or D gene. The third virus, hrBO1Pr-B, was a variant of Pr-RSV-B that did not appear to be a recombinant and whose altered host range we attribute to mutation. Analysis of the host range of all three viruses by infection of selectively resistant cells and by interference testing indicates that all use the subgroup B receptor on chicken cells and the subgroup E receptor on turkey cells. These viruses may be analogous to the polytropic recombinant viruses recently found to be associated with leukemia in some strains of mice. PMID- 6244566 TI - Isolation and sequence of the gene for iso-2-cytochrome c in Saccharomyces cerevisiae. AB - The two apocytochrome c proteins of yeast are coded for by separate genes. Iso-2 cytochrome c differs from the iso-1 protein at 17 positions within a homologous sequence of 108 amino acids. The previously cloned iso-1-cytochrome c coding sequence has been used to identify lambda-yeast recombinant phage containing the gene for iso-2-cytochrome c. The latter protein contains the dipeptide Ala-Ala which is coded for by the nucleic acid sequence G-C-N-G-C-N. The recognition specificity of restriction endonuclease Fnu4HI for G-C-N-G-C provided a rapid means of locating the region of the cloned fragment which codes for iso-2 cytochrome c. The DNA sequence of this gene has been determined and compared with that of the iso-1-cytochrome c locus. There is no intervening sequence within the gene for iso-2-cytochrome c. At 45 of the 91 positions for which iso-1- and iso-2 cytochrome c have the same amino acid, the codons differ. Such third position variation does not occur within the region coding for amino acids 70-80, the protein sequence that is also most conserved among all eukaryotic cytochromes c. PMID- 6244567 TI - Oxidative mechanisms of monocyte-mediated cytotoxicity. AB - Human monocytes stimulated with phorbol myristate acetate were able to rapidly destroy autologous erythrocyte targets. Monocyte-mediated cytotoxicity was related to phorbol myristate acetate concentration and monocyte number. Purified preparations of lymphocytes were incapable of mediating erythrocyte lysis in this system. The ability of phorbol myristate acetate-stimulated monocytes to lyse erythrocyte targets was markedly impaired by catalase or superoxide dismutase but not by heat-inactivated enzymes or albumin. Despite a simultaneous requirement for superoxide anion and hydrogen peroxide in the cytotoxic event, a variety of hydroxyl radical and singlet oxygen scavengers did not effect cytolysis. However, tryptophan significantly inhibited cytotoxicity. The myeloperoxidase inhibitor cyanide enhanced erythrocyte destruction, whereas azide reduced it modestly. The inability of cyanide to reduce cytotoxicity coupled with the protective effect of superoxide dismutase suggests that cytotoxicity is independent of the classic myeloperoxidase system. We conclude that monocytes, stimulated with phorbol myristate acetate, generate superoxide anion and hydrogen peroxide, which together play an integral role in this cytotoxic mechanism. PMID- 6244568 TI - Enhanced drug-metabolizing capacity within liver adjacent to human and rat liver tumors. AB - Cytochrome P-450 content (nmol/g of liver) differed within regions of rat liver according to proximity to intrahepatically implanted Morris hepatoma 7795 or 5123D. Liver adjacent to tumor had higher microsomal cytochrome P-450 content, decreased DNA content (mg/g of liver), and unaltered cytochrome c reductase activity compared to histologically indistinguishable liver far-removed from the tumor. Liver either adjacent to or far-removed from tumor contained markedly more cytochrome P-450 and higher cytochrome c reductase activity but less DNA than transplanted Morris hepatomas 7795 and 5123D that were grown intrahepatically. Compared to intramuscular implants of these same tumors, intrahepatically implanted Morris hepatomas 7795 and 5123D had increased cytochrome P-450 content. Tumor-containing liver from two human subjects revealed regional changes in cytochrome P-450-mediated monooxygenases similar to those observed in rats. These results suggest that histomorphically nontumorous mammalian liver directly adjacent to intrahepatic tumors exhibits previously unsuspected biochemical alterations. PMID- 6244569 TI - Molecular cloning of infectious integrated murine leukemia virus DNA from infected mouse cells. AB - The lack of an endonuclease EcoRI site in the AKR murine leukemia virus (MuLV) DNA genome was utilized to molecularly clone, in Charon 4A lambda DNA, integrated infectious AKR MuLV DNA isolated from productively infected mouse cells. Three lambda-mouse recombinants (clones 614, 621, and 623) were selected by virtue of their reactivity with AKR MuLV [32P]cDNA. Clones 614 and 623 contained the complete AKR MuLV DNA flanked by nonviral cell sequences of which no more than 100 base pairs beyond the viral DNA appear to be shared. DNAs from both clones 614 and 623 were highly infectious for mouse cells and yielded N-tropic ecotropic MuLV; the specific infectivity of the DNA and the titer of the derived virus was more than 10-fold higher with 623. Clone 621 contained only some viral DNA and was not infectious under similar conditions. PMID- 6244570 TI - Generation of oncogenic mouse type C viruses: in vitro selection of carcinoma inducing variants. AB - Type C retroviruses are endogenous in most vertebrate species. These viruses generally are of low pathogenicity in their natural hosts. Variants that contain cell-derived transforming genes have been isolated infrequently in the past upon continued passage in vivo. We report here a procedure that allows the isolation of new mouse leukemia-, sarcoma-, and carcinoma-inducing type C viruses entirely in cell culture. The viruses generated after passage in chemically transformed mouse cells and selectron in epithelial mink lung cells produced pulmonary adenomas and adenocarcinomas and also ovarian carcinomas. Viruses with cell transforming capacity, as determined by their ability to induce normal murine or mink cells to form progressively growing colonies in soft agar, appeared only transiently (2-4 days) after acute infection of "spontaneously" or chemically transformed mouse cells by nontransforming helper viruses. These transiently appearing transforming viruses can be "captured" by selecting the cells that respond to their newly acquired growth-stimulating ability. This system may lend itself to the systematic isolation of tissue-specific transforming functions from any cell that can be efficiently infected by retroviruses. PMID- 6244571 TI - Presynaptic membrane potential affects transmitter release in an identified neuron in Aplysia by modulating the Ca2+ and K+ currents. AB - We have examined the relationships between the modulation of transmitter release and of specific ionic currents by membrane potential in the cholinergic interneuron L10 of the abdominal ganglion of Aplysia californica. The presynaptic cell body was voltage-clamped under various pharmacological conditions and transmitter release from the terminals was assayed simultaneously by recording the synaptic potentials in the postsynaptic cell. When cell L10 was voltage clamped from a holding potential of -60 mV in the presence of tetrodotoxin, graded transmitter release was evoked by depolarizing command pulses in the membrane voltage range (-35 mV to + 10 mV) in which the Ca(2+) current was also increasing. Depolarizing the holding potential of L10 results in increased transmitter output. Two ionic mechanisms contribute to this form of plasticity. First, depolarization inactivates some K(+) channels so that depolarizing command pulses recruit a smaller K(+) current. In unclamped cells the decreased K(+) conductance causes spike-broadening and increased influx of Ca(2+) during each spike. Second, small depolarizations around resting potential (-55 mV to -35 mV) activate a steady-state Ca(2+) current that also contributes to the modulation of transmitter release, because, even with most presynaptic K(+) currents blocked pharmacologically, depolarizing the holding potential still increases transmitter release. In contrast to the steady-state Ca(2+) current, the transient inward Ca(2+) current evoked by depolarizing clamp steps is relatively unchanged from various holding potentials. PMID- 6244572 TI - Early nerve-muscle synapses in vitro release transmitter over postsynaptic membrane having low acetylcholine sensitivity. AB - Functional nerve-muscle synapses form rapidly in cultures of embryonic chicken spinal cord and muscle cells. As early as 30 min after nerve processes first contact muscle fibers they are able to release stimulus-evoked neurotransmitter. This release was detected only after wave-form averaging because of the exceedingly low amplitude of the synaptic potentials. This small size was likely due to a postsynaptic effect, because the electrophysiologically assayed acetylcholine sensitivity of the synaptic muscle membrane was low and did not differ significantly from extrasynaptic levels. Transmitter release was elicited both from along the lengths of nerve processes and from active growth cones. PMID- 6244573 TI - Stress-induced release of prolactin: blockade by dexamethasone and naloxone may indicate beta-endorphin mediation. AB - Basal levels of immunoreactive (ir) beta-endorphin, corticotropin (ACTH), and prolactin (PRL) in plasma of male rats decrease after dexamethasone pretreatment (400 microgram/kg at 24 hr and 200 microgram/kg at 2 hr before). Inescapable electric footshocks increase ir-beta-endorphin, ACTH, and PRL plasma levels and this effect is blocked by dexamethasone pretreatment. Morphine (20 mg/kg) also increases ir-beta-endorphin, ACTH, and PRL levels. Dexamethasone pretreatment blocks the morphine-induced release of ir-beta-endorphin but does not prevent the morphine-induced release of PRL. Naloxone, the opiate antagonist, decreases basal plasma levels of PRL and partially blocks the stress-induced increase of PRL, but it has no effect on the basal or stress-induced release of ir-beta-endorphin. These results are consistent with the proposal that beta-endorphin may interact with an opiate receptor involved in the regulation of PRL secretion. PMID- 6244575 TI - Autoradiographic localization of gamma-aminobutyric acid (GABA) receptors in the rat cerebellum. AB - [3H]Muscimol was used in the light microscopic autoradiographic localization of gamma-aminobutyric acid (GABA) receptors in the rat cerebellum. The binding of [3H]-muscimol to the slide-mounted tissue sections had all of the characteristics associated with a GABA receptor. It was saturable with appropriate kinetic constants and was blocked only by other GABAergic drugs. Autoradiographic studies revealed a very high density of receptors over the granule cell layer, a low level over the molecular layer, and negligible receptor binding over white matter. This suggested a high localization of GABA receptors to granule cells, which is supported by other neurochemical studies. The autoradiographic procedure used here should be a useful method in further studies of receptors requiring high sensitivity and increased anatomical resolution. PMID- 6244574 TI - Differences in glycosylation patterns of closely related murine leukemia viruses. AB - The nature of the carbohydrate chains in the major envelope glycoprotein of murine leukemia virus, gp70, and its cellular precursor has been investigated. A difference in the oligosaccharide composition of gp70 from an ecotropic murine leukemia virus (Akv) and three recombinant dual-tropic viruses [mink cell focus inducing viruses (MCFs)] derived from Akv was demonstrated. Glycosidase digestion and gel filtration were utilized to identify the two classes of N-asparagine linked oligosaccharides, high-mannose and complex. The gp70 of the ecotropic virus contained only N-linked oligosaccharides of the complex type. In contrast, the gp70s of the dual-tropic viruses contained both high-mannose and complex oligosaccharides. Analysis of gp70 glycopeptides from an MCF-related xenotropic virus showed an elution profile similar, but not identical, to profiles of the MCFs. The gp70 precursors isolated from cells infected with Akv or MCF virus contained N-linked oligosaccharides that were exclusively of the high-mannose type. Comparison of the high-mannose oligosaccharides of the MCF gp70 precursors with those of the corresponding gp70s indicated that very little further processing of the high-mannose residues in the gp70s had occurred. The presence of the high-mannose oligosaccharides in the envelope glycoprotein of the dual tropic viruses results from altered carbohydrate processing. The conservation of this altered carbohydrate pattern in a number of hosts and under various conditions of growth suggests that the viral protein structure is the primary factor in determining the different mode of glycosylation of the MCF gp70s. Thus, these viral glycoproteins provide an important model system for studying the relationship between protein structure and patterns of glycosylation. PMID- 6244576 TI - Host nuclear proteins expressed in simian virus 40-transformed and -infected cells. AB - Two new families of host proteins (Mr, 48,000 and 55,000), in additional to the viral large (T) and small tumor antigens, are precipitable, with anti-T antiserum, from cells transformed or infected by the DNA tumor virus simian virus 40 (SV40). Rabbit anti-mouse 48,000 protein antiserum reacts specifically with SV40-infected or -transformed mouse cells to give nuclear staining indistinguishable from T-antigen staining but does not react with SV40 transformed human cells which nevertheless have structurally analogous 48,000 proteins, nor does it give nuclear fluorescence with untransformed mouse cells. Comparison of the partial proteolytic digests of the 48,000 proteins from cultured cells of various mammalian species shows that they are structurally related but not related to the 55,000 or large T-antigen proteins. The 55,000 proteins from the various mammalian species were also structurally related. PMID- 6244577 TI - A role for cyclic AMP in expression of developmentally regulated genes in Dictyostelium discoideum. AB - Starved cells of Dictyostelium discoideum begin to synthesize a new class of developmentally regulated proteins at about 13 hr of the 24-hr developmental program, concomitant with the formation of tips on the tight cell aggregates [Alton, T. H. & Lodish, H. F. (1977) Dev. Biol. 60, 180--206]. Continued synthesis of these proteins is normally dependent upon the integrity of the multicellular aggregates, because cells that have been disaggregated at 13 hr and shaken in suspension for 5 hr do not make these proteins. We show here that addition of 20 microM cyclic AMP to suspension cultures of disaggregated 13-hr cells caused synthesis of most of these late proteins to be maintained. Translation in an in vitro wheat germ system of total cellular RNA isolated from these cyclic AMP-stimulated suspension cells, or from normal aggregates, generated several proteins that were not encoded by the RNA isolated from equivalent suspension cells which had not been treated with cyclic AMP or from preaggregation cells. We conclude that cyclic AMP has a direct role in maintaining the synthesis of aggregation-dependent Dictyostelium proteins and in maintaining the level of the corresponding mRNAs. PMID- 6244578 TI - Isolation and characterization of polyoma virus mutants able to develop in embryonal carcinoma cells. AB - Embryonal carcinoma (EC) mouse cells have been shown to be resistant to infection by retroviruses and small oncogenic DNA viruses, including simian virus 40 and polyoma. When allowed to differentiate, in vitro or in vivo, EC cells become as susceptible to these viruses as differentiated mouse cell lines are. In order to study the relationships between differentiation of EC cells and viral expression, we have isolated and characterized several polyoma mutants that can express early and late functions in undifferentiated EC cells. These mutants, which arose spontaneously during high-multiplicity infection of PCD3 cells (a differentiated fibroblast-like cell line derived from PCC3 EC cells), were selected on PCC4 cells (undifferentiated EC cells) and twice plaque purified. Restriction enzyme analysis of the DNA from several mutants has shown that they all exhibit an additional sequence located in the Pvu II endonuclease fragment 4, close to the junction between Hpa II endonuclease fragments 3 and 5. The size of the insertion varies from 10 to 50 base pairs. The biological properties, including oncogenicity, transforming ability, host range, and burst size of the mutants so far analyzed are similar to those of wild-type virus. PMID- 6244579 TI - Isolation of diploid human lymphoblast mutants presumably homozygous for ouabain resistance. AB - From a mass culture of diploid human lymphoblasts we have isolated a subline resistant to 1 muM ouabain, and from this, a subline resistant to 10 muM ouabain. These sublines occurred spontaneously, but similar mutants were induced with 10 fold increased frequency by treatment with mutagens, in which case they could be selected as clones in soft agarose. Scatchard plot analyses of ouabain binding indicated that the subline resistant to 1 muM ouabain retained an average of 39% of the high-affinity ouabain receptors of the parental lymphoblast line, and the subline resistant to 10 muM ouabain retained an average of 8.4%. The ouabain binding site is known to be located in the Na(+),K(+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) molecule, an essential cell membrane enzyme that mediates ion transport. Studies on Na(+),K(+)-ATPase activity, using (86)Rb in the absence and presence of ouabain, indicated that our parental lymphoblasts contained one population of Na(+),K(+)-ATPase molecules highly sensitive to ouabain inhibition, the subline resistant to 10 muM ouabain contained one population relatively insensitive to ouabain, and the subline resistant to 1 muM ouabain contained both populations. Thus, the moderately resistant subline appears to be heterozygous for ouabain resistance, probably containing a structural mutation in the ouabain receptor region of the Na(+),K(+)-ATPase molecule in one of the two homologous loci for this enzyme, whereas the highly resistant subline derived from it appears to be homozygous, containing an additional mutation in the other Na(+),K(+)-ATPase locus. PMID- 6244580 TI - Organization of kappa light chain genes in germ-line and somatic tissue. AB - We studied the organization of the kappa light chain genes in germ-line (sperm) and somatic (embryo) tissues. We constructed a plasmid containing a DNA insert coding for the kappa chain MOPC 167 and used the Southern blotting technique to determine the organization of kappa variable and constant region genes. In the haploid genome of the mouse there is only one constant region gene detectable and it has the same organization in sperm and embryo DNAs. There are several variable region genes in sperm and embryo that are related to the Vk167 gene. The organization of the V genes in sperm and embryo DNAs is identical. These results show that there is no rearrangement of variable region genes (or "minigenes") during early embryogenesis. PMID- 6244581 TI - Altered nerve growth factor in fibroblasts from patients with familial dysautonomia. AB - Nerve growth factor was measured in cultured human skin fibroblasts from controls and from patients with familial dysautonomia and dystonia musculoram deformans. Cells from these sources grown over a range of cell densities contained similar levels of beta-nerve growth factor as measured by radioimmunoassay. Results of bioassay demonstrated that the nerve growth factor from dysautonomic cells was only approximately 10% as active per ng of immunoreactive protein as that from control and dystonic cells. Treatment of fibroblasts with the beta-adrenergic agonist isoproterenol resulted in a 17- to 170-fold rise in the cyclic AMP content of both control and dysautonomic cells in 10 min. The content of immunoreactive beta-nerve growth factor in control fibroblasts increased 50--300% after 3--4 hr of exposure to isoproterenol. At no time, throughout a 7.5 hr period, was there a change in the amount of immunoreactive beta-nerve growth factor in the dysautonomic cells. These studies suggest that the molecular basis of the genetic defect in familial dysautonomia may lie in processing of the precursor or in the structure of the biologically active beta subunit of nerve growth factor. PMID- 6244582 TI - Plasmids containing insertion elements are potential transposons. AB - We studied in vivo recombination between the plasmid pHS1, a temperature sensitive replication mutant carrying tetracycline resistance, and pSM1, a small plasmid carrying one copy of the insertion element IS1. Recombinant plasmids were found by selection for tetracycline resistance at 42 degrees C. Their formation was independent of recA function. Analysis of the physical structures of various recombinant DNA molecules with electron microscopy and restriction endonucleases revealed that pSMI was integrated at its IS1 into numerous sites on pHS1, giving rise to a duplication of IS1 in the same orientation at both junctions. Nucleotide sequence analysis of recombinant plasmids and their parental plasmid DNA revealed that nine nucleotides at a target site were duplicated at the junction of each IS1. This phenomenon implies that plasmids containing a translocatable DNA element can be potential transposons. PMID- 6244583 TI - Functional implantation of a solubilized beta-adrenergic receptor in the membrane of a cell. AB - When the beta-adrenergic receptor of turkey erythrocytes was solubilized by deoxycholate, it retained its potential to activate an adenylate cyclase system. Electron microscopy showed that true solubilization had apparently been achieved; no residual membrane or vesicle structure was found. After removal of deoxycholate and addition of phospholipid, the reprecipitated beta-adrenergic receptor was implanted in the cell membrane of Friend erythroleukemia cells by using a chemical fusion method recently developed. Membranes prepared from the cells demonstrated 30-fold stimulation of the Friend cell adenylate cyclase by the implanted beta-adrenergic receptor. The function of the indigenous prostaglandin E(1) receptor of the Friend cells was not much affected by the implantation of large amounts of the foreign receptor. Activity mediated by the beta-adrenergic receptor reached 60% of the activity obtained with fluoride. The implanted receptor is therefore considered to be efficiently coupled to the adenylate cyclase system. The major difficulties hitherto preventing solubilization of hormone receptors and subsequent reconstitution of their function have been overcome by the approach developed in the present work. Conditions of solubilization need preserve only the receptor because all other components, even those unidentified as yet, can be supplied in excess by the adenylate cyclase system of the cell in which the receptor will be implanted. Subsequent recoupling of the receptor to the adenylate cyclase is performed in the native insoluble state of these molecules. Thus, the components need not be subjected to the hazards of solubilization in a common detergent as is usually required in reconstitution procedures. The importance of using implantation as an assay for a functional receptor in the course of purification and the likelihood that the procedure can be adapted to other receptors for hormones and neurotransmitters are discussed. PMID- 6244584 TI - Purification of a factor that restores translation of vesicular stomatitis virus mRNA in extracts from poliovirus-infected HeLa cells. AB - It was previously shown that the poliovirus-induced inhibition of translation of capped mRNAs can be reversed by a protein found in preparations of the eukaryotic initiation factor eIF-4B [Rose, J. K., Trachsel, H., Leong, K. & Baltimore, D. (1978) Proc. Natl. Acad. Sci. USA 75, 2732--2736]. This "restoring factor" has now been purified from a high-salt wash of rabbit reticulocyte ribosomes by taking advantage of its tight association with factor eIF-3 at low salt concentrations. It did not copurify with the major Mr 80,000 polypeptide of eIF 4B preparations but did copurify with a Mr 24,000 polypeptide previously shown to bind to the cap structures of mRNAs [Sonenberg, N., Rupprecht, K. M., Hecht, S. M. & Shatkin, A. J. (1979) Proc. Natl. Acad. Sci. USA 76, 4345--4349]. Both the electrophoretic mobility and the tryptic peptide pattern of the restoring factor were indistinguishable from those of the cap-binding protein, and the restoring factor could be crosslinked to the 5'-terminal cap on mRNA. Thus, is appears that poliovirus inhibits cellular protein synthesis by inactivation of some crucial property of the cap-binding protein. PMID- 6244585 TI - Agonist-promoted coupling of the beta-adrenergic receptor with the guanine nucleotide regulatory protein of the adenylate cyclase system. AB - Binding of the beta-adrenergic agonist [3H]hydroxybenzylisoproterenol to the beta adrenergic receptor of rat reticulocyte membranes results in the coupling of the receptor to the guanine nucleotide regulatory protein associated with the adenylate cyclase system. This regulatory component, referred to as the G protein, was identified by its specific [32P]-ADP-ribosylation catalyzed by cholera toxin. Incubation of [32P]ADP-ribosylated rat reticulocyte membranes with the [3H]hydroxybenzylisoproterenol agonist prior to membrane solubilization and gel exclusion chromatography resulted in the coelution of the 42,000 Mr [32P]ADP ribosylated G-proteins with the agonist-occupied beta-adrenergic receptors. The receptor-G-protein complex was not formed when receptors were unoccupied or occupied with antagonists at the time of solubilization. Incubation of rat reticulocyte membranes with [3H]hydroxybenzylisoproterenol in the presence of guanine nucleotides reversed or prevented the formation of this receptor-G protein complex. These data provide direct evidence for the molecular interactions promoted by agonist occupancy of beta-adrenergic receptors. It is probable that the formation of a receptor-G-protein complex is crucial for catecholamine stimulation of the adenylate cyclase enzyme and, hence, transmembrane information transfer. PMID- 6244586 TI - Coated vesicles transport newly synthesized membrane glycoproteins from endoplasmic reticulum to plasma membrane in two successive stages. AB - The G protein of vesicular stomatitis virus is a transmembrane glycoprotein that is transported from its site of synthesis in the rough endoplasmic reticulum to the plasma membrane via the Golgi apparatus. Clathrin-coated vesicles have been purified from CHO cells infected with vesicular stomatitis virus and shown to contain G protein in amounts nearly stoichiometric with clathrin. Pulse-chase experiments have demonstrated that this G protein is a transit form and have revealed that G is transported to the cell surface in two successive waves of coated vesicles. The oligosaccharides of G1 protein carried in the early wave are of the "high-mannose" variety which can be cleaved by the enzyme endoglycosidase H; the oligosaccharides of G2 protein in the second, later wave are resistant to endoglycosidase H. The early wave is therefore proposed to correspond to transport of G protein in coated vesicles from the endoplasmic reticulum to the Golgi apparatus, where the oligosaccharides are processed and resistance to endoglycosidase H is conferred; the succeeding wave would represent transport from the Golgi apparatus to the plasma membrane. PMID- 6244587 TI - Enhancement of free radical reduction by elevated concentrations of ascorbic acid in avian dystrophic muscle. AB - It has been postulated that the degenerative process in dystrophic muscle results from increased concentrations of free radicals, peroxides, or lipid hydroperoxides. Therefore, the reduction of the free radical tanol (2,2,6,6 tetramethyl-4-piperidinol-1-oxyl) by extracts of muscles of dystrophic and normal chickens was studied. Pectoral (white) and thigh (red) muscles were used. For initial rate measurements, the various muscle extracts were added to an equal volume of 0.2 mM tanol. Reaction mixtures were introduced into the EPR cavity in a standard aqueous flat cell. Rates were measured by continuously monitoring the decrease in signal amplitude of the center (MI = 0) solution tanol EPR resonance line (in-phase first harmonic absorption signal). With extracts from dystrophic white muscle, the reduction rate was 75% faster than normal, whereas in dystrophic red muscle extracts the rate was normal. This agreed with previous observations that white muscle is more severely affected than red in dystrophic chickens. The primary reductant was identified as reduced ascorbic acid, and the rate of reduction of tanol correlated directly with the concentrations of ascorbic acid in the various muscle extracts as shown by chemical analysis. The results suggest an involvement of the intracellular redox status in the pathogenesis of avian muscular dystrophy. PMID- 6244588 TI - Enhancement of phospholipid transfer from Sendai virus to erythrocytes is mediated by target cell membrane. AB - Transfer of phospholipid from the envelope of Sendai virus to erythrocyte membrane was measured by using spin-labeled phosphatidylcholine. The transfer was enhanced autocatalytically above a threshold dose (about five adsorbed viruses per cell). There was an inflection point in the time course of transfer, after which the transfer was greatly accelerated. The time to reach the inflection point became shorter with increased viral dose. The transfer reaction was markedly enhanced above 19 degrees C and the inflection point was observed above this temperature. There was negligible transfer from trypsin-treated virus to erythrocyte membrane, but the transfer was greatly enhanced by intact virus. The enhancement was larger with increased amount of intact virus, and the inflection point was observed in the transfer curves. All the kinetic data can be satisfactorily analyzed by a model which assumes that the virus modifies the cell membrane at the attachment site, the modification is propagated in the membrane, and transfer of phospholipid to the modified sites is greatly enhanced. The propagation rate is estimated as approximately equal to 10(-11) cm2s-1 and the activation energy as 13 kcal mol-1 (54 kJ mol-1). The viral F glycoproteins are suggested as a possible entity for the modification and its propagation: they are introduced into the target cell membrane by envelope fusion, diffuse laterally, and enhance both phospholipid exchange and envelope fusion with viruses attached to the membrane sites. PMID- 6244589 TI - recA protein-catalyzed strand assimilation: stimulation by Escherichia coli single-stranded DNA-binding protein. AB - The single-stranded DNA-binding protein of Escherichia coli significantly alters the strand assimilation reaction catalyzed by recA protein [McEntee, K., Weinstock, G. M. & Lehman, I. R. (1979) Proc. Natl. Acad. Sci. USA 76, 2615- 2619]. The binding protein (i) increases the rate and extent of strand assimilation into homologous duplex DNA, (ii) enhances the formation of a complex between recA protein and duplex DNA in the presence of homologous or heterologous single-stranded DNA, (iii) reduces the rate and extent of ATP hydrolysis catalyzed by recA protein in the presence of single-stranded DNA, (iv) reduces the high concentration of recA protein required for strand assimilation, and (v) permits detection of strand assimilation in the presence of the ATP analog, adenosine 5'-O-(O-thiotriphosphate). Single-stranded DNA-binding protein purified from a binding protein mutant (lexC) is considerably less effective than wild type binding protein in stimulating strand assimilation, a result which suggests that single-stranded DNA-binding protein participates in general recombination in vivo. PMID- 6244590 TI - Analysis of viral DNA sequences in hamster cells transformed by herpes simplex virus type 2. AB - Herpes simplex virus type 2 (HSV-2) DNA was treated with four restriction endonucleases (EcoRI, HincIII, Bgl II, and Xba I) and eight fragments were purified and labeled with 32P in vitro. The kinetics of renaturation of each of the fragments was measured in the presence of DNA extracted from 333-8-9, a hamster cell line transformed by UV light-inactivated HSV-2 strain 333, and from a series of cloned derivatives and their tumor lines. All of the lines examined contained a partial set of viral sequences present at only a few copies per cell. Passage of the cell lines in tissue culture or in animals resulted in partial loss of viral DNA. Two blocks of sequences were present in most of the lines examined; those mapping at positions 21--33 of the HSV-2 genome were detected in seven of seven cell lines tested and those at positions 60--65 were detected in six of eight. Other sequences from the L component can also be present in the DNA of HSV-2-transformed hamster cells. PMID- 6244591 TI - Initiation of DNA replication by the Escherichia coli dnaG protein: evidence that tertiary structure is involved. AB - The dnaG protein of Escherichia coli initiates DNA replication by synthesizing primer oligonucleotides for elongation by DNA polymerae. The experiments reported here probe the nature of the nucleic acid element recognized by the dnaG protein. Three well-separated groups of nucleotides within the negative-strand origin of the single-stranded phage phi K are protected by the dnaG protein against nuclease digestion. DNA as far as 115 bases from the start site of primer synthesis is involved in binding of the dnaG protein to the replication origin. One molecule of dnaG protein could protect all of these nucleotides if the DNA were folded into a higher-order tertiary structure. Protection of the phi K origin by dnaG protein requires DNA binding protein, and it does not occur if the group of protected nucleotides most distant from the start site is removed from the template. There is no binding of dnaG protein to the complementary strand of the phi K origin-region DNA. The observed protection of the positive strand is due to a functional nucleic acid-protein complex. PMID- 6244593 TI - Crystallization of part of the mitochondrial electron transfer chain: cytochrome c oxidase--cytochrome c complex. AB - Cytochrome c oxidase (ferrocytochrome c oxygen oxidoreductase, EC 1.9.3.1) was purified from beef heart mitochondria by affinity chromatography. Phospholipids were removed by washing the oxidase with detergent on the affinity column; 1 mole of cardiolipin remained per mole of heme a. The oxidase was mixed with excess cytochrome c in 1.5% (wt/vol) cholate to form a complex. Slow removal of the detergent from the mixture by dialysis resulted in crystallization of cytochrome oxidase in the form of a 1:1 complex with cytochrome c. The chemical composition and spectrophotometric properties of the crystal are described. Increasing the solubility of a hydrophobic membrane protein by combination with hydropholic ligand is demonstrated as a maneuver for crystallizing the membrane protein. PMID- 6244592 TI - Actin nascent chains are substrates for cyclic AMP-dependent phosphorylation in vivo. AB - Two-dimensional gel electrophoresis of extracts of S49 mouse lymphoma cells labeled with [35S]methionine in the presence of inducers or analogs of cyclic AMP reveals a protein that both affinity purification and peptide mapping show to be a form of nonmuscle actin. This actin species also exhibits cyclic AMP-dependent labeling with [32P]phosphate, and, after acid hydrolysis, 32P label is found associated with phosphoserine. Phosphorylated actin does not appear when cells prelabeled with [35S]methionine are treated with an inducer of cyclic AMP in the presence of emetine, an inhibitor of protein synthesis; this suggests that only the nascent form of actin is a substrate for cyclic AMP-dependent phosphorylation. As well as differing slightly in isoelectric points, beta and gamma actins are found to yield different partial proteolytic cleavage products with staphylococcal protease. This microheterogeneity in the major cellular actin component is repeated in both the metabolically labile delta/epsilon actin and phosphorylated actin, suggesting that these three forms of actin derive from the same two gene products. PMID- 6244594 TI - Integrated and free viral DNA in hamster tumors induced by BK virus. AB - BK virus (BKV)-induced tumors in hamsters were investigated for the presence of viral DNA by the blot-transfer hybridization technique. Several viral genomes per cell were found in tumor tissues and in their derived cell lines and clones. Most of the detected viral genomes were integrated into the cellular DNA, but some tumors also contained free viral DNA sequences. Integration patterns were different from each other, and many different integration sites were available on the cellular or on the viral DNA or on both. Typical features of integration patterns were found in ependymomas, which were the most frequent (72%) among BKV induced tumors. Readily detectable viral DNA sequences were only found in neoplastic tissues, but traces of BKV DNA were also present in the apparently normal portion of the brain of an animal that had developed an ependymoma and in the brain (but not in the liver) of another animal 15 days after virus inoculation. A cell line and a single-cell clone derived from a tumor had hybridization patterns considerably simpler that the pattern of the original tumor, lacking several integrated viral genomes and all free viral sequences. PMID- 6244595 TI - Deposition of fibronectin in the course of reverse transformation of Chinese hamster ovary cells by cyclic AMP. AB - The Chinese hamster ovary (CHO) cell, like other transformed cells, has lost the fibronectin deposit around its membrane. Treatment with cyclic AMP derivatives restores the typical fibroblastic deposit of fibronectin. Thus, the reverse transformation process induced by cyclic AMP (cAMP) in the CHO cell restores this important property as well as other morphological, biochemical, and growth behavioral characteristics of the normal fibroblastic state. The fibronectin deposit occurs significantly later in time than do other characteristics of the reverse transformation reaction and may therefore reflect a metabolic action that requires other cAMP effect to precede it. The restoration of fibronectin deposition in response to cAMP derivatives is also exhibited by vole cells transformed by avian sarcoma virus, but it is not by HeLa cell. Addition of Colcemid, which disrupts microtubules, to CHO cells containing a fibronectin deposit induced by cAMP derivatives causes little or no erosion of the deposit, but cytochalasin B, which disrupts 5-nm microfilaments, eliminates it completely. Thus, various features of the action of cAMP derivatives on CHO and related cells require integrity of the cellular microfibrils--in some cases microtubules only, in some cases 5-nm microfilaments only, and in some cases both classes of fibrils. PMID- 6244596 TI - In vitro inhibition of cell growth, collagen synthesis, and prolyl hydroxylase activity by triamcinolone acetonide. PMID- 6244597 TI - Changes in the concentration of cytidine 3',5' monophosphate (cyclic CMP) in regenerating rat liver. PMID- 6244598 TI - Human coronavirus OC43 serum inhibitor and neutralizing antibody by a new plaque reduction assay. PMID- 6244599 TI - Enhanced HSV recovery from neuronal tissues of latently infected rabbit. PMID- 6244600 TI - Radiation damage to nucleosides and nucleotides. I. An ESR study of uridine-5' phosphate.2Na+ single crystals. PMID- 6244601 TI - Enhancement effects of high-energy neon particles on the viral transformation of mouse C3H1OT1/2 cells in vitro. PMID- 6244602 TI - ESR of photoproduced nitroaromatic radicals: correlation between photolysis and radiolysis. PMID- 6244603 TI - [5-nucleotidase activity of rat liver in radiation sickness and the administration of ATP]. PMID- 6244604 TI - [Urographic and angiographic diagnosis of Wilm's tumor (author's transl)]. AB - Twelve cases of Wilm's tumor were examined: By intravenous pyelography alone in eight children and by pyelography and angiography in four adults. Intravenous pyelography showed characteristic displacement of the calyceal structures and displacement of the renal pelvis. Angiography gave detailed information regarding the vascular supply to the mass, the degree of vascularity, presence and number of tumor vessels and degree of pooling of contrast material in the tumor. Vascular penetration through the capsule of the kidney was not always consistent to perirenal tumor infiltration. By angiography one case of bilateral Wilm's tumor and two cases with metastases were discovered. PMID- 6244605 TI - Computed tomographic detection of nonbeta pancreatic islet cell tumors. AB - Twenty-five patients with nonbeta pancreatic islet cell tumors were examined by computed tomography (CT). In eight patients (32%), the primary pancreatic tumor was identified, and in ten patients (40%), hepatic metastases were seen. Only one of the eight tumors seen on CT was loager tha 10 cm; the other seven ranged from 4 to 9 cm in diameter. Tumors in ectopic locations or possible cellular hyperplasia rather than a discrete tumor may account for the relative insensitivity of CT visualization, particularly among patients with Zollinger Ellison syndrome. PMID- 6244606 TI - Echographic and radionuclide detection of hepatoma. AB - The clinical, echographic, radionuclide and CT studies of 19 patients with tissue proved hepatoma were reviewed retrospectively. All patients had undergone ultrasound examination while 18 also had 99mTc-sulfur colloid studies, and 11 had gallium scans. Ultrasonically, the lesions were classified as discrete, sonodense (six cases), discrete sonolucent (five cases), disorganized hepatic parenchyma (six cases), and normal parenchyma (two cases). All sulfur colloid studies showed areas of decreased uptake, while all gallium scans showed relative increased uptake in the area of decreased sulfur colloid activity. It was concluded that radionuclide imaging is more accurate than ultrasound in the diagnosis of hepatome. PMID- 6244607 TI - Opiate receptor binding and analgesic effects of the tetrahydroisoquinolines salsolinol and tetrahydropapaveroline. AB - Salosolinol and tetrahydropapaveroline bind to opiate receptors in rat brain with affinities of 6.2 and 1.95 x 10(-5)M respectively. Their ability to displace 3H naloxone is decreased about 4-fold by 100 mM sodium ion. Both of these agents have antinociceptive effects when given to rats intraventricularly. Their potency is comparable to the enkephalins, and their effect is blocked by naloxone. PMID- 6244608 TI - CO2-sensitivity of stretch receptors in the marsupial lung. AB - Discharge activity in single fibres of the vagus of the brush tailed possum was examined for evidence of pulmonary CO2 receptors by artificially ventilating the lungs with gas mixtures which preserved, abolished or reversed the normal tidal oscillation in FCO2. No specific CO2 receptors were observed. A quantitative study of the CO2 sensitivity of thirteen pulmonary stretch receptors was carried out after stabilizing FACO2 at high (6.4-7.8%), low (1.4-2.5%) as well as intermediate values. In addition receptor responses to a series of sustained augmenting inflations were examined at different intrapulmonary CO2 concentrations. All thirteen receptors showed CO2 sensitivity, their frequency of discharge being reduced by hypercapnia and increased by hypocapnia. Five were low threshold receptors which discharged throughout the ventilatory cycle while the remaining eight were only phasically active. High threshold receptors were more sensitive to FACO2 changes than were low threshold units. The results from the series of augmenting inflations suggest that it is the receptor's threshold, but not its sensitivity, to tracheal pressure that is modulated by the co2 signal. PMID- 6244609 TI - Intercostal and abdominal muscle afferent influence on medullary dorsal respiratory group neurons. AB - Studies were performed on anesthetized, paralyzed, artificially ventilated cats. Phrenic (C5) efferent activity, dorsal respiratory group (DRG) neuron activity in the vicinity of the medullary solitary tract complex, and thoracic dorsal root compound action potentials were recorded during electrical stimulation of intercostal and lumbar nerves. DRG neurons were identified by their firing pattern and response to lung inflation. Phrenic activity (PA) was inhibited by stimulating external intercostal nerves T3-T10, internal intercostal nerves T3 T12, lateral branch of the main intercostal nerves T6-T12, or lumbar nerves 1-2. Stimulation of lower (T9-T11) intercostal or lumbar nerves produced a short duration (10-20 msec) facilitation of PA prior to the inhibition. Facilitation and inhibition of PA were correlated with recruitment of afferent fibers from muscle proprioceptors. Inspiratory neurons (I alpha and I beta) in the DRG were inhibited simultaneously with PA regardless of the nerves stimulated. DRG neurons which fired in phase with lung inflation (P cells) were unaffected by nerve stimulation even though PA was inhibited. Lower intercostal nerve (T9-T11) stimulation produced a brief facilitation of medullary neuron activity simultaneous with facilitation of PA. It is concluded that intercostal and abdominal muscle proprioceptor afferents, and perhaps cutaneous afferents, reflexly alter the activity of DRG inspiratory neurons (I alpha, I beta) which drive the phrenic motoneurons. The inhibitory effect is not via P cells but may be via other interneurons in close proximity to the I cells. PMID- 6244610 TI - [Sports and ulnar neuropathies]. PMID- 6244611 TI - Rheumajecta in the treatment of rheumatoid arthritis. AB - A double-blind controlled trial of Rheumajecta in rheumatoid arthritis demonstrated lack of effect of this compound and unacceptable side-effects. It was not felt ethically justifiable to complete the trial. PMID- 6244612 TI - [Importance of computer tomography in paediatric diagnostics of abdominal and pelvic tumours (author's transly]. AB - In a joint study conducted by the University Clinic of Radiology, Graz, and the Medical University Clinic, Innsbruck, the results of computer tomography examinations of the abdomen and pelvis in 23 cases of tumours in children are discussed. In children, computer tomography resents special difficulties on account of the very poorly developed fatty layers between the organs and the increased incidence of movement artifacts. The importance of computer tomography for the diagnosis of abdominal and pelvic tumours is discussed. PMID- 6244613 TI - [Infectious mononucleosis. Cytology and immunological significance]. PMID- 6244614 TI - [Epstein-Barr virus]. PMID- 6244615 TI - [Mononucleosis syndromes excluding infectious mononucleosis]. PMID- 6244616 TI - A case of virilizing luteoma. PMID- 6244617 TI - [Bone metastases of prostatic neoplasms with reference to the histological type and local tumor stage]. AB - In prostatic cancer the frequency of osseous metastases - detected earliest by bone scintigraphy - amounts to 21.8% at the time of histological verification of the primary tumour. This frequency depends on the histological type of the prostatic carcinoma and yields 10.5% in uniform adenocarcinomas and 40.4% in pluriform carcinomas. The rate of metastases in the uniform adenocarcinomas rises with increasing histological dedifferentiation. The percentage of prostatic carcinomas with pluriform pattern in comparison with uniform adenocarcinomas rises markedly, corresponding to the local tumour extent (T2 = 36.4%, T3 = 52.2%, T4 = 61.1%). For the purpose of stage-related therapy of prostatic cancer, histological grading and clinical staging, including bone scanning, are absolutely essential. PMID- 6244618 TI - Cytochrome c and the evolution of energy metabolism. PMID- 6244619 TI - Neurotransmitter release from a vertebrate neuromuscular synapse affected by a food dye. AB - The food dye erythrosine (Erythrosin B; FD & C No. 3) was applied to isolated neuromuscular synapses in the frog, and its effects on the spontaneous quantal release of acetylcholine were examined with electrophysiological techniques. At concentrations of 10 muM or greater this anionic dye produced an irreversible, dose-dependent increase in neurotransmitter release. This increase did not depend on the presence of calcium ions in the bathing medium. These increase did not depend on the presence of calcium ions in the bathing medium. These results suggest that erythrosine might prove a useful pharmacological tool for studying the process of transmitter release, but that its use as a food additive should be reexamined. PMID- 6244620 TI - High-molecular-weight immunoreactive beta-endorphin in extracts of human placenta is a fragment of immunoglobulin G. AB - A high-molecular-weight protein with beta-endorphin- and adrenocorticotropin immunoreactivities was isolated from extracts of human placenta after several purification steps, including immunoadsorption with a well-characterized antiserum raised to beta-endorphin. This protein was identified as the heavy chain of the human immunoglobulin class IgG1. These results have led to the recognition of homologies in the amino acid sequences of these physiologically unrelated molecules. They also suggest caution in accepting immunological competence as the sole criterion of the chemical identity of a ligand. PMID- 6244621 TI - Phorbol ester action is independent of viral and cellular src kinase levels. AB - Treatment of normal chick embryo fibroblasts with phorbol myristate acetate causes those cells to express many of the phenotypic properties of virally transformed cells and also enhances the expression of transformed properties in Rous sarcoma virus-transformed chick embryo fibroblasts. We report here that phorbol myristate acetate has little or no effect on the level of protein kinases encoded by the viral src or endogenous sarc genes. PMID- 6244622 TI - [Interest of the dosage of serum ferritin in hemodialyzed patients (author's transl)]. AB - The ferrous stock evaluation can be done to-day in a repetitive manner through the serum ferritin radio-assay. In 33 hemodialyzed patients, the ferrous lack is frequent and was found with a rate of 62%. It is profound in four cases and concealed in 17 cases. The serum ferritin has no correlation with the ordinary hematologic and biologic parameters. Its value stays in the Ag HBs positive patient. The oral ferrous treatment to the patient with a low ferritin rate (less than 30 ng/ml) induces a ferritin and a hemoglobin rate increased, so confirming the therapeutic efficacy when done with a rational prescription. PMID- 6244623 TI - [Evolution of motor nerve conduction and Hoffmann reflex in 100 patients with chronic renal failure treated by periodic hemodialysis (author's transl)]. AB - The study of motor nerve conduction (MNC) and H. reflex was carried out on 100 chronic uraemic patients, fifty-four males and fourty-six females, treated by periodic hemodialysis. The MNCV is more frequently normal in females than in males. Periodic hemodialysis improves MNCV but sometimes uraemic neuropathy appears with hemodialysis. The MNCV is oftener improved than H. reflex latency. Results are neither significantly improved by a greater number of hemodialysis seances nor in function of the different dialyzers. Any kidney activity does not modify the nerve conduction. PMID- 6244625 TI - [The respiratory function in muscular dystrophies (author's transl)]. AB - The principal cause of death in Duchenne muscular dystrophy (DMD) results from a respiratory involvement, classically defined as a restrictive syndrome. The respiratory function in muscular dystrophies (MD) was studied using spirometer respiratory function tests on 190 patients, classified into five distinct groups, according to accurate clinical and genetic findings. The three adult types of MD (Becker type, limb girdle type, facio-scapulo-humeral type) are characterized by pulmonary function approaching normal. DMD is always characterized by a restrictive syndrome. A high significant difference between adult and DMD types is confirmed by statistical analysis. In DMD, vital risks are variable according to variations of the level of absolute value of vital capacity. It is useful to distinguish three types in DMD: major involvement or type I, severe involvement or type II, moderate or mild involvement or type III. PMID- 6244624 TI - [Propionicacidemia. A report on two cases (author's transl)]. AB - Two cases of propionicacidemia are reported. The first patient was a child aged 16 months with psychomotor retardation, severe disturbances of wakefulness, and vomiting; the second case concerned a new-born baby with metabolic acidosis and neurological disorders. In both cases the diagnosis of propionicacidemia was made after the discovery of ketonuria, and raised blood ammonia and glucose levels. Appropriate dietary measures led to great improvement in the first case, and nearly normal psychomotor development in the second case at 7 months of age. Problems related to biotin sensitivity, leucine intolerance, and raised blood ammonia levels are discussed. PMID- 6244627 TI - [A case of strangulated congenital diaphragmatic hernia with necrosis and rupture of the colon and herniation into a left hemithorax in an adult (author's transl)]. AB - This is a case report of a successful repair of congenital diaphragmatic hernia in a 48 years old male that contained the transverse colon which was strangulated and ruptured in the left thoracic cavity. It was approached in two stages. First through a laparotomy the proximal part of the transverse colon was divided. The side going to the hernial sac was sutured and the proximal stump was anastomosed to the descending colon. In a second stage, two days later, through a felt thoracotomy the strangulated and ruptured colon was resected and the distal stump of the transverse colon was sutured and the hernia repaired. PMID- 6244626 TI - [Tuberculous abscess of the central nervous system (author's transl)]. AB - A case of tuberculous abscess of the cerebellum is reported by the authors. A check-up of concerned literature of ten-past years is drawn up. Diagnosis is seldom raised before surgery in spite of former or evolved tuberculosis. Histology and bacteriology are essential for a supportive therapy. The prognosis is favorable in seventy three per cent of the cases. This pathology must not be forgotten in patients who imigrate from countries of high endemic level of tuberculosis. PMID- 6244628 TI - [A review of congenital aneurysms of the coronary arteries and report on two cases (author's transl)]. AB - The authors report on 2 cases of congenital aneurysms of the coronary arteries and review the published literature. A total of 17 cases were found, which respond to their criteria fo; congenital coronary artery aneurysms discovered in patients after selective arteriography investigation. One of their cases was found to have aneurysms of the hepatic and distal renal arteries (vascular dysplasia?). PMID- 6244629 TI - [A case of chorea (author's transl)]. AB - The author reports a case of Huntington's chorea improved after treatment with tiapride, and discusses the complex pathogenic features of this affection and the therapeutic difficulties encountered. PMID- 6244630 TI - [Cystic degeneration of the popliteal artery. Report of one case (author's transl)]. AB - One case of this curious lesion is presented. At this occasion a short study of the literature is made. The authors particularly insist on the necessity of complete resection of the lesion and to reestablish arterial flow by a short venous graft. PMID- 6244631 TI - [Bone marrow and renal involvement in sarcoidosis. Report of a case (author's transl)]. AB - Sarcoidosis is proteiform and localisations to mediastinum, lung, nodes, skin and glands are the most frequent. The involvement to bone marrow and kidney are rarely described. The authors report in this paper a case of sarcoidosis revealed by hypercalcemia with bone marrow and kidney lesions, and discuss their morphologic aspect and frequency. PMID- 6244632 TI - [A case of solid tumor of the small omentum (author's transl)]. AB - With regards to an observation of a solid tumor of the small "epiploon", the authors recall the exceptionnal character of the primitive small tumors of the "mesenterium". Such cases pose a histological problem because, when dealing with the "mesenterium", the various criteria for benignity or malignity are difficult to appraise due to the peculiar tissue structure. A pre-operative-selective "arteriogram" cannot be dispensed with this type of tumor. Outside of the diagnostic possibilities offered, this "arteriogram" will be the basis for the treatment given since the possibilities of removal are limited by the connection between the tumor and the vessels. Furthermore due to the histological difficulties posed by these tumors it is desirable to treat them as potentially malignant material and include the removal, even if limited, of the corresponding digestive segment. PMID- 6244633 TI - [The radiolesions of the small bowel (author's transl)]. AB - The irradiation of the pelvic abdominal cancers extends beyond the centre of the tumour and may induce actinic digestive lesions. The bowel and more rarely the small bowel--which is the subject-matter of our study--are concerned by those radiolesions that are favoured by therapeutic overdose, post-operative adhesions fastening the bows, radio-surgical or chemicostatic associations, and lastly by vascular or nutritive deficiencies. One may distinguish between two kinds of lesions, depending on the lapse of time before their coming out and on the symptoms. The early or acute types are characterized by a radio-mucitis and give an exsudative enteropathy with anorexia, vomiting, diarrhoea and loss of weight, of which the diagnosis is easy because it occurs during the irradiation and lessens at the end of the treatment. The late radiolesions of the small bowel are characterized by sclerosis and chronic endarteritis and, after a longlasting period of latency, give varied symptoms: disordered intestinal transit which sometimes is irreversible, perforation, fistula, syndrome of malabsorption, giving often rise to be mistaken for a recurrence of the cancer. The treatment varies whether the lesion is segmental or diffuse. In the first case, the failure of the medical means accounts for the surgical cutting away or the internal derivation; in the second case, the digestive mutilation which would result from an enlargement of the lesion commands to be more cautions and to call for the methods of parenteral feeding and digestive setting to rest. PMID- 6244634 TI - [The bony scan at 99m Tc pyrophosphate in the chronic kidney deficiency treated by hemodialysis (author's transl)]. AB - The bony scan at 99m Tc pyrophosphate of thirty chronic hemodialyzed patients have been classified in four groups of increasing fixation according to Olgaard's criterions. The clinical, radiological symptoms of renal osteodystrophy the alkalin phosphatases and the PTHi rate have been compared. Twenty-six scans show a noticeable fixation (stage II) or an important one (stage III--eleven patients). The third stage patients have more important radiographical symptoms, a more important rate of alkalin phosphatases and PTHi rate than those of the second stage. According to our observations and those of literature, the scan at 99m Tc PP allow an early and faithful diagnosis of renal osteodystrophy. It seems to represent the increase of the osteoid immature tissue, which is the usual characteristic of the renal osteodystrophy. PMID- 6244635 TI - [Strategy for laboratory tests of thyroid function (author's transl)]. AB - Clinical findings suggesting hyperthyroidism should be confirmed by the following basic tests of thyroid function: serum T3 and T4, and iFT4. In the case where there is contradiction between the T3 and T4 values, hyperthyroidism may be confirm by the absence of effect of TRH on serum TSH level. Clinical findings suggesting hypothyroidism should be confirmed by the following basic tests: serum T3 and T4, iFT4, and serum TSH which also will be greatly helpful in the differentiation of primary or secundary hypothyroidism. When there is an absence of parallelism between total and free T3 and T4 determinations, it is necessary to look for a possible abnormality in the binding protein. In vivo explorations (radio-iodine uptake, scintigraphy) and other assays should be proposed in view of clinical findings but should not be systematically prescribed. PMID- 6244636 TI - [Gastric mucus glycoproteins: structure, functions and pathology (author's transl)]. AB - O-glycosylated glycoproteins are the main constituents of gastric mucus. They are responsible for its viscosity and for its gel-forming properties. Recent advances accomplished over the last years on its physical and chemical characterization are briefly reviewed. Many issues remain still unsettled concerning the modification of its structure and composition in diseases as well as details of its biosynthesis and its pharmacology. PMID- 6244637 TI - [Anti-inflammatory treatment of ankylosing spondylitis (author's transl)]. AB - Anti-inflammatory treatment of ankylosing spondylitis is based on the administration of the various non-steroid anti-inflammatory agents made available since the introduction of phenylbutazone. As with this later compound they each have a group of patients that respond to their administration and are able to tolerate them. In this way, physical education exercises can be undertaken for the spine and chest several times a day, which is the only therapy capable of improving prognosis and avoiding stiffening and spinal deformities. A study protocol is proposed that has the advantage of allowing a rapid evaluation of the efficacy and tolerance of the products successively administered for short periods, by using scored evaluation criteria. The most effective and better tolerated compound for each patient can thus be determined. This protocol is valid for both general practice or therapeutic study use, and in open or double blind trials. PMID- 6244638 TI - [Recent aspects of tuberculous peritonitis (22 cases in the adult) (author's transl)]. AB - The authors show in this work the principal features of 22 tuberculous peritonitis cases seen between 1967 and 1977 affecting 17 Black Africans, 2 West Indians and 3 French (metropolitan) Caucasians cirrhotic or alcoholic. The 9 ascitic forms are not in the majority but it is worthwhile to consider a laparoscopy with peritoneal and/or hepatic biopsy where there is abdominal pain or unexplained fever. In most cases there exists one or several other tuberculous sites particularly pleural, pulmonary, hepatic, or in the cases of the Africans mediastinal lymphadenopathy. The means of diagnosis are commented upon with stress on the importance of peritoneoscopy and biopsies. The prognosis is good provided that antituberculous treatment is employed over a period of one year, with or without the temporary conjunction of corticosteroids. PMID- 6244639 TI - [Blood and bone marrow abnormalities in primary lung cancers (author's transl)]. AB - Blood and bone marrow abnormalities accompanying cancers have been known for a while, without yet being understood. The study of 89 patients having lung cancers leads to the following observations: thrombocytosis is frequent and should be considered as a diagnostic criterion; anemia is often associated and we have noticed a correlation between the two. The bone marrow abnormalities shown on biopsy are also frequent, presenting mainly (54/104) as irritative type. This histological pattern becomes a criterion of prognosis, since one should interpret it as a bone marrow reaction to the implantation of cancerous cells. Lastly, no relationship has been found between the blood count and the bone marrow pattern. PMID- 6244640 TI - [Two cases of tuberculosis of the skull cap (author's transl)]. AB - The authors report two cases of tuberculosis of the skull cap. The first in a Black African with heterozygous sickle cell disease also presenting with: tuberculosis of the cervical lymph nodes, subcutaneous frontal tumefactions bacteriologically confirmed to be of tuberculous origin, multiple lacunae of the vault from the same origin; the second case is an Asian woman having a multifocal tuberculous osteitis involving the skull, spine, pelvis and probably the same affection in the spleen. These cases are a reminder that the principal features of tuberculosis of the skull vault are very often associated with other tuberculous lesions, and to the problems of diagnosis it entails; the existence of a subcutaneous tumefaction of the vault or of any accessible site one can aspirate and/or perform biopsy constitutes a diagnostic aid. PMID- 6244641 TI - [Undetected cryoglobulinaemia may alter the serum protein results and mask dysglobulinaemia (author's transl)]. AB - By reporting a case of massive cryoglobulinaemia where precipitation of the cryoglobulins occurred at 35 degrees C but with no apparent clinical symptoms the authors want to draw attention to the fact that if cryoglobulinaemia remains undetected it may alter the serum protein results and mask dysglobulinaemia. However if protein electrophoresis is carried out at the same time, it is possible to detect a slight abnormality due to cryoglobulin fraction not entirely removed during centrifugation of the blood sample. This finding should incite one to look for cryoglobulins according to the usual procedure (at 37 degrees C) as well as to measure serum proteins on a sample also collected at 37 degrees C. Thus occasionally one happens to detect such dysglobulinaemia and if all results point to a diagnosis of myeloma -- as was the case here -- treatment can then be started early with advantage. PMID- 6244642 TI - [Calcified and suppurated epidermoid cyst of the spleen (author's transl)]. AB - Reporting a case of epidermoid cyst of the spleen revealed on suppuration brings the authors to review the classification of epidermoid cyst. These are benign tumors in the main present clinically with left hypochondrium pain and the possibility to palpate a splenomegaly or mass in this hypochondrium. The diagnostic approach includes diverse investigations, in particular a series of radiological examinations; surgical intervention will confirm and avoid complications. PMID- 6244644 TI - [Surgical treatment of complex forms of congenital heart malformations associated with situs inversus (nine cases) (author's transl)]. AB - Although are, situs inversus is nevertheless encountered in the surgical treatment of heart malformations. This series concerns 1 000 patients who where operated with heart-lung by-pass between 1974 and 1977. In nine cases, the heart was in the situs inversus position and the cardiac malformations associated with this condition, were complex. Yet the results were comparable to those obtained when the heart was in the normal position. PMID- 6244643 TI - [Present clinical appearances of tuberculosis in hospital practive: their diagnostic difficulties (author's transl)]. AB - Even if tuberculosis has become now rare in France, the frequency of new cases in general hospital practice remains 1,4% of incomers. More than 50% of man and 80% of women attacked with tuberculosis are 60 years old or more. Pulmonary tuberculosis represents 60% of these cases but other localizations are various and multifocal in 22,8% of cases. Two points are emphasized: the difficulties of the diagnosis in some specially misleading cases and the fatal prognosis of 8,5% of cases. PMID- 6244645 TI - [Serological diagnosis of Staphylococcus aureus infections using anti-A beta telchoic acid antibodies assay (author's transl)]. AB - 225 contol subjects, 12 hospitalized staphylococcus free (34 sera) and 16 S. aureus infected patients (79 sera) were tested for anti-A beta teichoic acid antibodies, using counter-immunoelectrophoresis. Anti-alpha and gamma haemolysins antibodies were dosed in parallel in 164 sera. Less than 5 per cent of control sera (3,11 per cent) have an antibody titre higher than 1/8; this titre is therefore selected as threshold level of positivity. Ten of the 12 hospitalized patients without staphylococcal infections are below this level. 31,6 per cent of staphylococcus infected patients have higher serum titers; only 3,7 per cent have no antibodies. In the others, a significant rise in titres is observed. There is no correlation between anti-alpha and gamma staphylolysin and anti-teichoic acid antibodies titres. The method suggested, both easy and rapid, could be used in association with anti-staphylolysin dosage for serological diagnosis of staphylococcal infections. PMID- 6244646 TI - [The diagnostic value of radiological examinations in Conn's syndrome: angiographic findings in 58 cases (author's transl)]. AB - Selective adrenal phlebography with measurement of hormone levels was used to investigate the majority of 58 cases of primary hyperaldosteronism. The authors stress the importance of pre-operative diagnosis of the lesion as surgery is indicated for adenomas only, and because of their small size they are often missed in adrenal scintigrams and on manual exploration during operation. They are in agreement with most other authors that adrenal phlebography is the most valid investigation, as it gives a precise diagnosis of the lesion in 92% of cases. The angiographic findings in the most common lesions are described, the difficulty in diagnosing peripheral small adenomas stressed, and the problems associated with the diagnosis of nodular hyperplasias outlined. They also underline the fundamental importance of selective hormone levels measurement, as these results are of equal value to those of the images themselves. PMID- 6244648 TI - [Cerebrospinal fluid rhinorrhea (author's transl)]. AB - A series of 140 surgical cases of CSF rhinorrhea have been reviewed, their diagnostic difficulties outlined and the possible etiologies and the modes of surgical approach explained. The localization of the leak is difficult in traumatic cases but if one searches diligently for the source with polytomography of the skull base as well as utilizing repetitive radioisotope studies, one can definitely find the source of the rhinorrhea. If the patient presents with purulent meningitis, a fistulous tract, acquired or congenital, should be sought and if present resected. Only precise surgical technique in and around the skull base in cases of rhinorrhea, allows total definitive recovery without recurrent leak and prevents post operative rhinorrhea in routine basal and trans-sphenoidal neurosurgical procedures. PMID- 6244647 TI - [Clinical, electrocardiographic and coronarographic findings in 31 patients with left coronary artery stenosis (author's transl)]. AB - The clinical, electrocardiographic, coronarographic and hemodynamic findings in thirty-one patients with left coronary artery stenosis were compared with those noted in patients with critical stenoses in all the three branches only. It was not possible to distinguish between the two groups of patients by comparing these results, and coronary arteriography is still the only valid diagnostic procedure. PMID- 6244649 TI - [Right-sided diaphragmatic hernias of late diagnosis (author's transl)]. AB - A normal diaphragm at birth cannot eliminate a right-sided diaphragmatic hernia, as the liver comes between thorax and abdomen. Diagnostic problems, pathogenesis and treatment are seen about two cases. PMID- 6244650 TI - [Left superior veina cava and endocardial stimulation (author's transl)]. AB - A left superior veina cava may be troublesome for endocardial lead's placement during permanent pace maker's implantation. We have operated upon one patient with this anomaly. We report the anatomic frequency of this congenital malformation and the technics used to obtain a satisfactory permanent pacing. PMID- 6244651 TI - [Edemas with hypernatremia. Mechanism and treatment (author's transl)]. AB - The discrepancy between the finding of hypernatremia--a manifestation of extra cellular fluid depletion--and the presence of edema--a manifestation of increased ECF--is best explained by the patient's inability to mobilize edemas to compensate intra-vascular dehydratation. Treatment must start by the administration of hypotonic solutions, as hypernatremia is dangerous for the brain. PMID- 6244652 TI - [Transient bone marrow aplasia associated with hepatitis. Possible effect of lithium therapy (author's transl)]. AB - A 70-year-old patient developed a bone marrow aplasia following the onset of an apparently infectious hepatitis. During the course of his illness he experienced episodes of severe sepsis, that were treated with antibiotics and leucocyte transfusions. The authors suggest that lithium therapy might be of benefit for such patients because of his granulopoietic properties. PMID- 6244653 TI - [Meningo-encephalitis due to Candida albicans (author's transl)]. AB - Meningo-encephalitis due to Candida albicans is frequently iatrogenic in origin and the factors leading to its appearance should be known (immunity disorders and more particularly indiscriminate prescribing of antibiotics). Diagnosis is usually difficult and direct examination of the CSF and culture on special media are necessary in order to demonstrate the presence o yeasts. Recovery is possible with present-day therapy (two out of the three cases reported). PMID- 6244654 TI - [Hypophosphatemic vitamin D resistant osteomalacia with parathyroid adenoma (author's transl)]. AB - The authors report a new case of parathyroid adenoma associated with hypophosphatemic vitamin D resistant osteomalacia. These troubles were simultaneously found. Major and isolated phosphate tubular loss was improved neither by parathyroidectomy nor vitamin D or 25 OHD therapy. On the contrary 25 OHD associated with oral phosphate intake was clinically, radiologically and histologically efficient. The actual pathogenic concepts about this affection are reviewed. PMID- 6244655 TI - [Piribedil, dopaminergic agonist and the cerebral neurovascular syndrom of the aging man (author's transl)]. AB - In the aging brain, there is an alteration of neurotransmettor systems, essentially catecholaminergics (dopamine, noradrenaline). The experimental works which show the agonist effect of piribedil on cerebral dopaminergic systems are presented. The results of the action of piribedil in the cerebral neuro-vascular syndrom are analysed. PMID- 6244656 TI - [Metoclopramide: interest in treatment of upper digestive burns (author's transl)]. AB - The main action of metoclopramide on the upper digestive tract is an acceleration of stomach draining. This effect is very useful to prevent pains due to gastro oesophageal reflux and bile reflux. PMID- 6244657 TI - [Often unrecognized cutaneous manifestations of strongyloidosis: linear dermatitis or larva currens (author's transl)]. AB - The linear dermatitis of "larva currens" is a typical manifestation of strongyliasis, however is generally too unrecognized. It is observed in about 7% of cases, more frequent in white race. Due to the migration of Strongyloides larvae in epidermis of sensitized person, it appears in form of rectilinear urticaria from 10--30 cm, developed from 12--48 hours and disappeared without leaving any trace. It can appear at any place of the body, sometimes in many places simultaneously. The total duration of the evolution similiar to that of strongyliasis can be developed during a many tenth of years. In reality the differential diagnosis is easy with filariasis (loa-loa) and specially with cutaneous larva migrans (ankylostomiasis, creeping eruption, larbish). The thiabendazole cures the strongyliasis nad its cutaneous manifestations in 85% of cases with a single oral dose of 6 tablets 6 x 250 mg). PMID- 6244658 TI - [Richter's syndrome and acute transformation: two terminal haematological complications of chronic lymphoid leukaemia (author's transl)]. AB - Two cases of CLL terminating in Richter's syndrome and in blastic crisis raise the problem of the physiopathological signification of these unusual complications. Richter's syndrome is described as a "histiocytic" lymphoma or a Hodgkin's disease supervening on a CLL. It does not seem that these two pictures have actually to be distinguished since clinical and haematological aspects are not different, and histopathologic studies show always atypical aspects with difficulty of an accurate diagnosis. Cases of blastic crisis of CLL are very uncommon. They correspond to the transformation of a CLL in acute lymphoblastic leukaemia. These two terminal complications of CLL suggest they may be interpreted as two pictures of the transformation of the same initial B cellular clone. This hypothesis, highly probable for the Richter's syndrome, has been actually demonstrated for the acute transformation of CLL. PMID- 6244659 TI - [Comparative study of oral and intravenous glucose tolerance test during pregnancy (author's transl)]. AB - The glucose tolerance has been studied in 140 non diabetic pregnant women by successively oral and intravenous glucose tolerance test, as described respectively by O'Sullivan and Conard. The results of both tests are grossly similiar, and are affected on the same way by the evolution of the pregnancy. The intravenous glucose tolerance test is the easiest and the most reproducible; however some extra diabetic factors can interfere and mainly this test is not sensitive enough to discriminate between the pathologic and borderline situations. For all these reasons the intravenous glucose tolerance test can be used as a screening test for diabetes mellitus during pregnancy. The oral glucose tolerance test is necessary only when the K value is abnormal or subnormal. PMID- 6244660 TI - [Three new cases of presacral tumor (author's transl)]. AB - Presacral tumors have miscellaneous histologic structures: some of them, among the most uncommon, are malignant tumors and lay it down that the extirpation must be the most complete as possible. Often they are uncovered when they compress adjoining organs (rectum, bladder, ureters, sacral plexus) and they appear voluminous, encrusted in the pelvic excavation, taking a rich vascularisation from surroundings. This adhesion involves a laborious extirpation, often hemorraegic, but needful even in benignant tumors. On this understanding and with the help of a good approach, pelvic organs can be decompressed with restricted risks of recurrence. PMID- 6244661 TI - [Analgesic effects of tiapride in man. A double-blind comparative clinical trial against placebo (author's transl)]. AB - A double-blind comparative study to estimate the effects of tiapride when compared to placebo was conducted in 29 patients with pain from cancer. Each patient acted for his own control. Excellent or good results were obtained in 14 cases with tiapride against 6 with placebo, and moderate or no results in 15 patients on tiapride and 23 on placebo. There is a highly significant statistical difference in favour of tiapride for efficacy, but no significant difference was noted between tolerance of tiapride and placebo. PMID- 6244662 TI - [Heterophil antibody negative infectious mononucleosis due to Epstein-Barr virus. A clinical, hematological and serological study of 14 cases (author's transl)]. AB - Fourteen patients admitted to the hospital for heterophil antibody negative infectious mononucleosis (IM) were studied; the causative agent was Epstein-Barr virus, as confirmed by the presence of anti-VCA antibodies (IgG and IgM) and the absence of anti-EBNA antibodies. The patients were from 2 to 69 years old, 7 being less than 10 years old while 4 were more than 45 years old. In all cases, asthenia and adenopathy were found and a deterioration in liver functions was present whenever it was looked for; jaundice occurred in 3 patients. In 6 cases fever persisted for several weeks. Leukocytosis and a high level of mononuclear cells were present in 8 patients and atypical lymphocytes in 10. Anti-EA titers were found to be high in the severe forms of illness. Clinical and laboratory features of these 14 heterophil negative IM patients were compared with a group of 21 heterophil positive IM patients studied under the same conditions; the most striking differences between the two groups were the frequency of patients under 10 and over 45 years old in the heterophil negative group, the frequency of abnormal liver function tests and of persistent fever, and a lower frequency of atypical lymphocytes. PMID- 6244663 TI - [Contribution of laparoscopy to the diagnosis of liver involvement by lymphoma. Results in 100 peritoneoscopies (author's transl)]. AB - The retrospective study of 100 peritoneoscopies in cases of hematocarcomas reveals an hepatic involvement in 23% of the patients. The clinical status, the diffusion of the lymph nodes involvement, the radio-isotope scanning and the liver enzymes are not reliable and cannot predict the liver involvement. The peritoneoscopy which allows several and guided biopsies is better than blind transcutaneous liver biopsy. PMID- 6244664 TI - [Results of the treatment of 250 cutaneous epitheliomas]. PMID- 6244666 TI - [Pseudocysts of the pancreas presenting in the kidney region. A report on two cases (author's transl)]. AB - Two cases of pseudocysts of the pancreas presenting in the kidney region are reported. The authors stress the value of renal and coeliomesenteric arteriography for establishing the etiological diagnosis of atypical cystic formations of the kidney. PMID- 6244665 TI - [Cytologic survey of CSF in the meningeal hemorrhages (author's transl)]. AB - We have selected a group of young patients, without any pathological past, admitted in the hospital after traffic accidents. CSF was examined at various periods after the accident as well on the cytological as on the biological point. If the lumbar punction is undertaken in the very few hours after the trauma or at the time of the onset of a meningeal syndrom, the presence of oxyhemoglobin may confirm the abnormal bleeding and makes difference with the stitching of a vessel during the punction. The presence of macrophages red blood cell containing may characterize a 2--3 days bleeding. The presence of macrophages containing iron pigment may confirm that the bleeding appeared at least 6--7 days before the cytological patterns and the chromoprotein assays provide a valuable help to the physiologist and may be applied to all types of meningeal hemorrhages. PMID- 6244667 TI - [74 by-passes on leg arteries (author's transl)]. AB - 74 by-passes on leg arteries have been performed during these last ten years at St Joseph's hospital to cure: femoropopliteal atherosclerotic occlusive disease (67 cases), aneurisms (5 cases), post-traumatic arteriovenous fistula (1 case), popliteal thrombosis on exostosis (1 case). The indication for operation was, in almost every case, carried on a distal advanced ischemia, followed by an imminent limb loss. In four cases, there existed an acute sensory and motor ischemia. The accumulated potency rate was 58.5% at 1 year and decreased progressively afterwards: 38.20% at 3 years and 21.6% at 5 years. However, the choice of a surgical technics doesn't find its justification in a long-dated prognosis for this operation, the aim of which being limb-salvage. In this prospect, the results are hopeful: 77% of the limbs have effectively been preserved at the end of the follow-up period. PMID- 6244669 TI - [Generalized fatal reactions to BCG vaccine]. PMID- 6244668 TI - [Metabolism and kinetics of ampicillin elimination in cirrhosis. Therapeutical consequences (author's transl)]. AB - In cirrhotic patients, the authors studied the modification of the pharmacokinetics of ampicillin in the plasma and in the ascitic fluid, as well as its concentration in the urine. The influence of the jaundice, the ascites and diuretics were studied. In cirrhosis, dilution and elimination of the antibiotic are modified, as is shown by the increase in T 1/2 alpha and T 1/2 beta. These anomalies seem to be due essentially to modifications in the distribution volume; the degree of hepatocellular insufficiency does not appear to be of importance. The ascites acts as an independent compartment, into which the antibiotic's passage is slight. The practical consequences are the following: less frequent injections, increasing of the fractionated doses, in situ injections of ampicillin in cases of infection of the ascitic liquid. PMID- 6244670 TI - [Fatal case of metformin-induced lactic acidosis after urography in a diabetic patient (author's transl)]. AB - The authors report a new case of lactic-acidosis in a diabetic patient receiving metformin. This patient, after urography developed an acute renal failure and a fatal lactic acidosis. Risks of urography in diabetic patients and guidelines for use of metformin are recalled; careful assessment of risk versus benefit for every proposed urography in diabetic patients never use metformin if creatinin is over 140 micromoles/liter, if an urography must be undergone, metformin must be stopped 3 days before urography and resumed only 3 days after it, if renal function allows it. PMID- 6244671 TI - [Hypo-uricemia due to renal uricosuria (author's transl)]. AB - A 49 years old healthy man was found to have major hypouricemia (0.2--0.5 mg/100 ml) with normal 24 hours urinary urate excretion (300 mg). The urinary clearance of uric acid was found to be very increased (100 ml/mn), higher than the clearance of creatinine (85 ml/mn). Urinary xanthine and hypoxanthine levels were normal. There was no other clinic or biologic trouble. PMID- 6244672 TI - [The association of lupus and Hodgkin's disease. A case history (author's transl)]. AB - The authors report the observation of a young woman 22 years of age having presented the clinical and biological manifestations of disseminated lupus erythematosis, followed more than one year later by the appearance of Hodgkin's disease. Several etiopathological hypothesis concerning this association have been discussed but the experimental work of Schwartz has permitted the finding of a common denominator for these two diseases: a RNA virus, type C. PMID- 6244673 TI - [A case of generalized reaction to BCG vaccine without apparent immunodeficiency and a fatal outcome (author's transl)]. AB - No immunodeficiency could be found in a case of generalized BCG infection. The therapeutic trials were unsuccessful, and the child died at the age of 19 months. PMID- 6244674 TI - [Dilution hyponatremia and conserved natriuresis in pulmonary tuberculosis (author's transl)]. AB - Association of dilution hyponatremia and normal natriuresis produce an inappropriate secretion of antidiuretic hormone. In this pulmonary tuberculosis case we report manifestations along with the other biological criteria of inappropriate secretion of antidiuretic hormone. All disturbances cease when pulmonary tuberculosis is cured. This syndrome may be due either to disturbance in the regulatory apparatus of antidiuretic hormone secretion or to the antidiuretic principle in tubercular lung tissue. PMID- 6244675 TI - [Association breast cancer-meningioma. Report of two cases (author's transl)]. AB - The theoretic and clinical interest of the association between breast cancer and meningioma is underlined. In both reported cases two women, which respectively two and three years ago, had undergone mastectomy operation due to breast cancer, showed symptoms and signs of cranial tumor. The operation revealed the diagnosis of meningioma in both instances permitting effective treatment of the lesion. PMID- 6244676 TI - [Treatment of frostbites. Analysis of results in twenty patients with buflomedil chlorhydrate (author's transl)]. AB - Twenty cases of mountain frostbites of various degrees are presented, showing that buflomedil hydrochloride allows an improvement of the usual treatment of frostbites. Two protocols were used: 1) in 8 patients, after the usual treatment (bath at 38 degrees C, dextran perfusion, heparintherapy, antibiotherapy), buflomedil hydrochlorhydrate was administered by perfusion of 8 vials/day, during 10 days; 2) in 12 patients, buflomedil was injected directly by intravenous route on their arrival in the Emergency room. When the injection is given early, a potentiation of the effects of the warm bath is observed, and in two cases, this therapy has perhaps allowed to avoid the amputation. PMID- 6244677 TI - Markers of human lymphocyte subpopulations in primary immunodeficiency and lymphoproliferative disorders. PMID- 6244678 TI - Metabolic aspects of immunodeficiency disease. PMID- 6244679 TI - Adjuvant chemotherapy with VM 26 and CCNU after operation and radiotherapy of high-grade supratentorial astrocytomas. AB - Thirty-one patients with histologically proven malignant (Grade III and IV) astrocytomas were randomly placed in one of two treatment schedules two weeks after gross total or subtotal tumor removal. One group (15 patients) received radiation therapy and adjuvant chemotherapy with VM 26 and CCNU once every four weeks, commencing four weeks after the completion of radiotherapy. The second group (16 patients) received radiotherapy alone. The duration of the progression free interval from operation to recurrence was measured to evaluate the effect of the adjuvant chemotherapy. The median free interval calculated by the computer analysis according to the method of Kaplan and Meier was 65.5 weeks for the chemotherapy group and 40.0 weeks for the control group. The difference is not statistically significant. From our experience, adjuvant chemotherapy should only be given to patients with residual or progressive tumors following radiation therapy. PMID- 6244680 TI - Etiology of gliomas. PMID- 6244681 TI - Raeder's syndrome. A clinical review. AB - The term "Raeder's syndrome," which now seems to mean any painful postganglionic Horner's syndrome, has been used in the past to describe patients with a wide variety of underlying pathology, including such serious lesions as middle cranial fossa neoplasms and such benign conditions as unilateral vascular headache syndromes. The purpose of this review which is based on the literature and some recent experience with 41 cases of Raeder's syndrome, is to help clarify this syndrome and to aid the clinician in its evaluation and treatment. Patients with Raeder's syndrome have been divided into three major groups. In the first group, the painful postganglionic Horner's syndrome is associated with multiple parasellar cranial nerve involvement and these patients require full neuroradiological investigation to uncover such lesions as local or metastatic tumors within the middle cranial fossa. The second and third groups do not have the multiple cranial nerve damage and their prognoses are benign. The characteristics, clinical investigation and medical therapy of each of these two benign groups are outlined and discussed. Extensive neuroradiological investigation is not recommended for patients in the second or third groups. Common to all three groups of Raeder's syndrome is the association of unilateral headache with the interruption of the postganglionic oculosympathetic fibers along the course of the internal carotid artery. PMID- 6244682 TI - Biopsy for microcalcification detected by mammography. AB - Fifty-two patients who were biopsied because of the presence of clustered microcalcifications on mammography, in the absence of any definable mass on x-ray or physical examination, were studied. Localization of the microcalcifications was obtained by measuring the area in relation to the vertical and horizontal axes from the nipple on both lateral and cephalocaudad views. Specimen radiography was obtained to ensure that the area with microcalcifications had been included in the specimen. Carcinoma was found in 17 instances (33%). In four (24%) the detected microcalcifications corresponded to fibrocystic disease, with carcinoma being found only in adjacent tissue with little or no calcifications. Precise localization and removal of only the area containing calcifications without excision of a generous margin of surrounding tissue may result in the exclusion of an adjacent carcinoma. PMID- 6244683 TI - Primary carcinoma of the trachea: mixed squamous and oat cell type. PMID- 6244684 TI - Metabolism of benzo[a]pyrene and 7,12-dimethylbenz[a]anthracene in chicken aortas: monooxygenation, bioactivation to mutagens, and covalent binding to DNA in vitro. PMID- 6244685 TI - Effect of silica and carrageenan on the survival of islet allografts. AB - Pancreatic islet cell allotransplantation has considerable potential in the treatment of diabetes mellitus. However, isolated islets appear to be particularly sensitive to rejection and attempts to prolong their survival in experimental animals have so far met with only limited success. In this study the effect of two macrophage suppressing agents, silica and carrageenan, has been investigated in a rat model. Islets from (August x AS) F1 donors were transplanted into AS recipients. Of 13 animals treated with i.v. carrageenan (5 mg/kg), only one had prolongation of graft survival compared to controls. There was indefinite survival in 7 of the 16 animals treated with i.p. silica (50 mg/100 g) and 2 additional animals died normoglycaemic. In an attempt to measure the effectiveness of these two agents in suppressing macrophage activity, the ability of the "fixed" macrophages of the mononuclear phagocytic system to clear particles from the circulation was measured using 125I-labelled microaggregated albumin. Although both carrageenan and silica reduced clearance values, it proved impossible to correlate the degree and duration of this suppression with the success or otherwise of the islet cell allografts. PMID- 6244686 TI - Mixed mesodermal tumors of urinary bladder: prognosis and management. AB - Three cases of mixed mesodermal tumors of the urinary bladder characterized by the simultaneous occurrence of malignant epithelial and mesenchymal elements in the same tumor are reported. Integrated therapy consisting of preoperative radiotherapy followed by radical cystectomy is recommended. Chemotherapy is best withheld until the nature of any metastatic disease has been confirmed histologically in order that the appropriate drugs can be administered. PMID- 6244687 TI - Functional morphology of spontaneous hyperplastic and neoplastic lesions in the canine pituitary gland. AB - The pituitary glands of 10 male and 29 female dogs of different breeds had diffuse hyperplasia and hypertrophy of growth hormone or prolactin cells. Immunoreactive adrenocorticotrophin/melanotrophin was in the frequent focal hyperplastic lesions and micro- and macroadenomas of both pars distalis and pars intermedia of old female dogs. Pituitary tumours of other functional cell types were not found. Focal hyperplastic and neoplastic lesions usually were accompanied by spontaneous nodular hyperplasia or adenomas of the adrenal cortex as well as by changes in serum adrenocorticotrophic hormone and cortisol levels. PMID- 6244688 TI - Zollinger-Ellison syndrome in three dogs. AB - The main clinical signs of three dogs with Zollinger-Ellison syndrome were vomiting, diarrhoea, poor appetite and weight loss. The diagnosis was confirmed by histological examination and by gastrin immunocytochemistry. Gastrin was extracted from pancreatic tumours of two dogs. Gastrin-component III predominated in one dog while gastrin-component II and gastrin-component III were demonstrated in almost equal amounts in the other dog. In one dog serum gastrin concentration was high. Postmortem examination revealed pancreatic tumours in all three dogs and metastases in the regional lymph nodes and liver in two. The pancreatic tumours contained three patterns of growth: solid, trabecular and acinar. Electron microscopy of liver metastases showed cells with secretory granules. In all three dogs there was an erosive oesophagitis and thick gastric mucosa caused mainly by glandular proliferation. Two dogs had erosions and ulcers in the duodenum, one also in the first part of the jejunum. Villous atrophy and cellular infiltration of the duodenal mucosa were found in all dogs. PMID- 6244689 TI - Malignant aortic body tumor with metastasis to bone in a dog. PMID- 6244690 TI - Maedi/visna: a review. AB - A brief history of the occurrence of maedi/visna or maedi/visna related diseases is given. The clinical features and diagnosis are described. Recent experimental work performed in an attempt to resolve the pathogenetic features of slowness and persistence of infection, characteristic of maedi/visna, is covered. A description of the epidemiology is given followed by possible methods of control. PMID- 6244691 TI - Isolation of a rhinovirus of bovine origin in the Sudan. AB - A virus isolated from the nasal secretions of a calf with acute respiratory disease was found to possess the general properties of rhinoviruses. Serologically it was related to the M-17 strain, a type 1 bovine rhinovirus, but distinct from the EC11 strain representing type 2. Seroconversion in neutralising antibody to the isolate was demonstrated in paired serum samples derived from the calf. This is the first report of bovine rhinovirus isolation in the Sudan and Africa. Whether bovine rhinoviruses play any significant role in bovine respiratory disease in the Sudan is not known and has yet to be determined. PMID- 6244692 TI - Interaction of an intranasal combined feline viral rhinotracheitis, feline calicivirus vaccine and the FVR carrier state. AB - Eight cats were vaccinated intranasally with a combined feline calicivirus/feline viral rhinotracheitis (FVR) virus commercial vaccine. Following intranasal challenge with a field strain of FVR virus and subsequent treatment with corticosteroid, no virus was recovered from any of the eight cats, while FVR virus was recovered following corticosteroid treatment from two of four unvaccinated and challenged controls. No evidence was found for the development of an FVR virus carrier state with the intranasal vaccine virus. PMID- 6244693 TI - Virus infections in cattle and sheep in Scotland 1975-1978. AB - Over the four-year period 1975-78 attempts were made to identify virus in samples from 1231 outbreaks of disease in cattle, and 682 outbreaks of disease in sheep. A virus identification was possible in 26 per cent of these disease outbreaks. The nature and significance of these virus infections is discussed. PMID- 6244694 TI - Oncogenic transformation by equine herpesviruses (EHV). I. Properties of hamster embryo cells transformed by ultraviolet-irradiated EHV-1. PMID- 6244695 TI - Studies on the relationship between 5' leader sequences and initiation of translation of adenovirus 2 and simian virus 40 late mRNAs. PMID- 6244696 TI - Replication of Theiler's murine encephalomyelitis viruses in BHK21 cells: an electron microscopic study. PMID- 6244697 TI - Effect of interferon treatment on vesicular stomatitis virus (VSV): release of unusual particles with low infectivity. PMID- 6244698 TI - Proteolytic enhancement of rotavirus infectivity: biology mechanism. PMID- 6244699 TI - Mechanism of interferon action. Interferon-mediated inhibition of simian virus-40 early RNA accumulation. PMID- 6244700 TI - Changes in parental vaccinia virus DNA after viral penetration into cells. PMID- 6244701 TI - Synthesis of circular DNA in avian tumor virus particles. PMID- 6244702 TI - Regulation of endogenous type C viruses: evidence for transcriptional control of AKR viral expression. PMID- 6244703 TI - Human leukocyte interferon induces 2', 5'-oligo (A) polymerase and protein kinase. PMID- 6244704 TI - The problem of host DNA synthesis in murine cytomegalovirus-infected cells. PMID- 6244705 TI - Induction and biological characterization of the Epstein-Barr virus (EBV) carried by the Jijoye lymphoma line. PMID- 6244706 TI - The role of brain scintigraphy in metastatic Wilms' tumor. PMID- 6244707 TI - Tetrahydrocannabinol as an antiemetic for cancer patients. PMID- 6244708 TI - [Radiation therapy and the characteristics of the course of laryngeal cancer in women]. PMID- 6244709 TI - [Ultrastructural study of a medullomyoblastoma (author's transl)]. AB - A third case in between twelve reported cases of medullo-myyoblastoma was investigated by electron microscopy. The muscle cells seemed to originate of proliferated endothelial cells. Because of the derivation from two blastodermic layers the tumour was considered a teratoid. PMID- 6244710 TI - [Cylindroma of the base of the skull with longstanding neurological disturbances. Anatomo-clinical correlation]. AB - The authors present the clinico-pathological correlation in a women who developed at the age of 43 years progressive pain in the left hemiface with motor and sensitive disorders of the left trigeminal nerve. Progressive involvement of the left IIIrd, IVth and Vth cranial nerves appeared with persistence of intractable facial pain which was not responsive to treatment by Tegretol, nor by thermocoagulation of the left Gasserian ganglion. Partial resection of a tumor was performed. The biopsy revealed its cylindromatous nature. The patient died after eight years of evolution. Autopsy confirmed an extensive tumoral invasion of the left temporal bone with invasion of the dura, the left cavernous sinus, and tumoral infiltration of the IIIrd, IVth, Vth and VIIIth cranial nerves on the left side. Metastases of the cylindromatous epithelioma were found in the liver and adrenals. The precise origin of the tumor could not be ascertained. PMID- 6244711 TI - Sinus histiocytosis with massive lymphadenopathy in a Japanese adult with unusually elevated EBV antibody titers. AB - A 35-year-old Japanese male was presented with massive lymphadenopathy in bilateral preauricular and submandibular regions for five years' duration without any complaints despite of no specific treatments. Laboratory examinations revealed neurtrophilia, elevated BSR, hypergammaglobulinemia with elevated IgG and IgM, positive CRP and RA, low percentage of T-cells in peripheral blood, impaired PHA blast transformation, and elevated EBV titers against viral capsid, early and nuclear antigens. Biopsy specimens demonstrated massive histiocytosis with hemophagocytosis in the sinuses and predominant mature plasma cells in the medulla, which were fairly well consistent with "sinus histiocytosis with massive lymphadenopathy" (ROSAI and DORFMAN). Ultrastructural study revealed histiocytes exhibiting avid phagocytosis of blood cells, epithelioid histiocytes with poor phagocytic activity, foamy storage histiocytes loaded with a large number of osmiophilic lipid granules and giant cells of various types. Pathogenesis of this apparently benign disease entity was briefly discussed, and its refractoriness against any specific therapy was emphasized. PMID- 6244712 TI - Clinicopathological study of coxsackie B viral myocarditis. AB - Autopsy cases of myocarditis caused by Coxsackie viruses in two infants, aged 5 years and 10 months and 12 years, and two adults, aged 24 years and 45 years, were presented. Of the four cases, three revealed a rise in serum neutralization titer to Cox B,4 virus and one to both Cox B2 and Cox B4 viruses. Compared with the adult cases, the 2 infant cases showed less inflammatory response with relatively prominent hypertrophy in the heart. Both of the adult cases revealed intensive inflammatory reaction. Extensive inflammatory cell infiltration remained in one of the adult cases though the case survived about 4 years after manifestation of the infection, suggesting possible involvement of immunological factors. PMID- 6244713 TI - Malignant fibrous histiocytoma of the maxillary sinus. AB - A case of malignant fibrous histiocytoma arising primarily in the left maxillary sinus is described. The patient, a 39-year-old male, who had suffered from sinusitis for 20 years, began to have paresthesia or sharp pain of the left side of the face and toothaches of the left maxilla. At operation a white fibrous tumor developing extensively from the lateral wall to the upper and medial walls of the left maxillary sinus and into the ethmoidal sinus was noted. Following a gradual progression of dyspnea, he died approximately one year after the onset in spite of radiation therapy and anticancer chemotherapy. An autopsy revealed recurrence of the tumor in the left maxillary sinus with wide-spread metastases to the lungs, pleurae, pancreas, kidneys and bone marrows. The direct cause of death was respiratory failure due to extensive growths of the pulmonary and pleural metastases. PMID- 6244714 TI - Cystosarcoma phyllodes of the breast with features of malignant fibrous histiocytoma. AB - A case of a 33-year-old female with metastasizing malignant cystosarcoma phyllodes of the left breast showing histologic features of malignant fibrous histiocytoma is reported. Metastases consisting of only undifferentiated mesenchymal cells were found in the lungs, liver, pleurae, kidneys, ileum, and vertebrae. Seven cases of fibrohistiocytic tumors of the breast previously recorded in the literature were reviewed. Although rare, this type of tumor should be included in the differential diagnosis of mesenchymal mammary tumors. PMID- 6244715 TI - On the role of cyclic AMP in the cytotoxic effect of fluoride. AB - The possible role of adenosine 3',5'-monophosphate (cAMP) in the cytotoxic effect of fluoride was investigated in fluoride sensitive mouse fibroblasts (LS) and a subline of LS resistant to 6 mM fluoride (FR6). In both cell lines, growth was inhibited by dibutyryl-cAMP, prostaglandin (PG)E2 and theophylline, FR6 being somewhat more sensitive to these agents than LS. FR6 had lower basal cAMP levels in the intact cells and lower basal adenylate cyclase activity in the homogenate preparation than LS, but the percentual response of intact cells or adenylate cyclase preparations to PGE1 or PGE2 was about the same in the two cell lines, and the sensitivity of the adenylate cyclase to fluoride was similar. No measurable increase in cAMP content was found in either LS or FR6 after exposure of the intact cells to various concentrations of fluoride for various times. The present results indicate that the development of fluoride resistance in these cells is not due to decreased sensitivity to cAMP, and probably not due to altered cAMP-formation in response to fluoride. The growth inhibitory and cytotoxic effects of fluoride in LS cells is probably not mediated through cAMP. PMID- 6244716 TI - A radioimmunoassay for cyclic AMP (cAMP) obtained by acetylation of both unlabeled and labeled (3H-cAMP) ligand, or of unlabeled ligand only. AB - A sensitive radioimmunoassay (limit of detection 7 +/- 1 fmol per tube) for cyclic AMP (cAMP) based on acetylation of both 3H-cAMP and unlabeled ligand was developed. Rabbit anti-cAMP antibodies had an apparent Ka for the acetylated ligand of 2 x 10(10) l/mol. When the unlabeled ligand only was acetylated an increased sensitivity was obtained without loss of specificity. PMID- 6244717 TI - [Abnormalities of the structures involved in the transmission of nociceptive messages in animals. A tool for pharmacologists]. PMID- 6244718 TI - [Interaction of antihypertensive drugs with alpha and beta adrenergic receptors in the central nervous system]. PMID- 6244719 TI - Structural modifications of gangliosides in synaptic membranes. PMID- 6244720 TI - Hydrolysis of gangliosides in micellar and liposomal dispersion by bacterial neuraminidases. AB - Aqueous dispersions of pure gangliosides contain micelles of these compounds. In this dispersion state, the rates of hydrolysis of the neuraminyl residues by bacterial neuraminidases are slowest. Incorporation of gangliosides into mixed dispersion with other lipids or into mixed micelles with bile salts considerably increases the reaction rates. The greatest reaction rates are obtained when di- or trisialogangliosides are incorporated into unilamellar vesicles of lecithin or sphingomyelin. PMID- 6244721 TI - Glycolipids and cell differentiation. PMID- 6244722 TI - Cell biological and immunological significance of ganglioside changes associated with transformation. PMID- 6244723 TI - Perturbation of CNS functions by antibodies to gangliosides. Speculations on biological roles of ganglioside receptors. PMID- 6244724 TI - Gangliosides as receptors for bacterial toxins and Sendai virus. PMID- 6244725 TI - Thyrotropin receptors and gangliosides. PMID- 6244726 TI - Gangliosides and synaptic transmission. PMID- 6244727 TI - Pseudogout and pyrophosphate metabolism. PMID- 6244728 TI - Scirrhous carcinoma of the pyloric channel and distal antrum. AB - The clinical, endoscopic, and pathologic features of 13 cases of scirrhous carcinoma of the pyloric channel and distal antrum are described and correlated with the radiographic findings. The lesions appear as smooth concentric narrowings, rigid and generally short. They are associated with outlet obstruction but without gastric or duodenal ulcerations. Features highly suggestive of pyloric muscular hypertrophy, such as indentation at the base of the duodenal cap and pyloric notch, may occur. Almost all cases had serosal invasion and lymphatic spread at surgery. The differential diagnosis and a short review of the pertinent literature is presented. PMID- 6244729 TI - Brachial plexus neuropathy. Three cases in children. AB - Brachial plexus neuropathy is an acute neurologic disorder characterized by pain, weakness, and atrophy of the muscle groups affected. Although well documented in the adult literature, relatively few cases have been reported in children. Despite the lack of knowledge concerning its etiology, and lack of an effective therapy, the long-term prognosis is excellent. It is perhaps for these reasons that spinal fluid analysis is not routinely performed during the acute phase of this illness. An evaluation of the clinical course of three children, together with epidemiologic data, suggests that early lumbar punctures and an extensive search for an infecting viral agent, notably coxsackievirus B, are warranted. PMID- 6244730 TI - Increased risk for lymphoma and glomerulonephritis in a closed population of cats exposed to feline leukemia virus. AB - Feline leukemia virus (FeLV)-associated diseases were observed in a household in eastern Connecticut having 134 cats over a period of five and a half years. FeLV positive cats had a much higher mortality rate (34.6 deaths per 1000 cat-months of follow-up) than did FeLV-negative cats (8.9 deaths per 1000 cat-months of follow-up). The leading cause of death was glomerulonephritis followed by lymphoma. The relative risk for virus-positive cats as compared to virus-negative cats for the two diseases was 9.9 and 9.6, respectively. The major risk factors for the development of lymphoma were virus positivity and low antibody titer to the feline oncornavirus-associated cell membrane antigen (FOCMA). No significant differences in cancer incidence were seen between the two major breeds (Abyssinian and Burmese) in the household. An older age at arrival in the house decreased death rates for all causes in the household, but it did not significantly affect death rates from lymphoma, although there was a positive trend. PMID- 6244731 TI - Hormones from tumors: are they ubiquitous? PMID- 6244732 TI - Radioimmunoassay of serum creatine kinase B isoenzyme in the diagnosis of acute myocardial infarction. Correlation with technetium-99m stannous pyrophosphate myocardial scintigraphy. PMID- 6244733 TI - Persistent transfusion-associated infectious mononucleosis with transient acquired immunodeficiency. AB - Trauma and blood transfusion led to profound, persistent infectious mononucleosis in a 21 year old man. Splenectomy and trauma had apparently produced transient immune deficiency which was complicated by osteomyelitis of a fractured tibia. The transfused blood probably contained Epstein-Barr virus (EBV). Infectious mononucleosis had ensued 25 days after a blood transfusion was given, antibodies to EBV appeared in his serum, and the infectious mononucleosis persisted for nearly two years. His immunity returned gradually to normal, but because of nonunion of the fracture site, which was infected by Staphylococcus aureus, above knee amputation was required. The acquired, transient immune deficiency to EBV and profound infectious mononucleosis seen in this patient is analogous to inherited, permanent immune deficiency to this virus in the X-linked lymphoproliferative syndrome. PMID- 6244734 TI - Pulmonary hypertension as a presentation of hepatocarcinoma. Report of a case and brief review of the literature. AB - A case, unique in the literature, is reported in which a primary carcinoma of the liver presented a right-sided heart failure and pulmonary hypertension. The diagnosis of hepatocarcinoma was established by needle biopsy of the liver. Later, postmortem examination demonstrated that the pulmonary arterial tree was severely compromised by multiple tumor microemboli, despite the persistent lack of characteristic roentgenographic abnormality in our patient. In reviewing the literature, we found rare cases of occult renal cell carcinoma, choriocarcinoma and one of occult hepatocarcinoma, which presented as pulmonary embolism. These were diagnosed by pulmonary embolectomy, human chorionic gonadotrophin levels or autopsy, respectively. In another small group of reported cases of known carcinoma (gastric, breast, colonic) the patients had a clinical picture of "idiopathic" pulmonary hypertension or of pulmonary hypertension with pulmonary metastases. Pulmonary hypertension in these cases resulted from carcinomatous lymphangitis and/or tumor microembolization, as in our case. We report this case to emphasize the necessity of including occult carcinoma in the differential diagnosis of pulmonary hypertension and right ventricular failure. PMID- 6244735 TI - Fetal heart block caused by cytomegalovirus. PMID- 6244736 TI - Silent corticotropic adenomas of the human pituitary gland: a histologic, immunocytologic, and ultrastructural study. AB - Among 300 surgically removed pituitary adenomas, 17 tumors containing immunoreactive 1-39 adrenocorticotropin (ACTH) and/or 19-39 ACTH, beta lipotropin, and alpha-endorphin but unassociated with clinical signs of Cushing's disease have been detected. These neoplasms were divided into basophilic adenomas with strong periodic acid-Schiff (PAS) and lead-hematoxylin positivity and chromophobic tumors with moderate or no PAS and lead-hematoxylin positivity. The former were densely granulated tumors with a fine structure strikingly similar to that of functioning corticotropic cell adenomas. The latter were sparsely granulated with varying ultrastructural patterns. The marked morphologic diversity suggests that these adenomas, despite their similar immunocytologic characteristics, represent more than one entity. Clinically, the most common finding was a rapidly progressing visual defect. An unusually high incidence of infarction (5 cases) and recurrence (5 cases) was noted, underlining the importance of correct morphologic diagnosis and careful follow-up. PMID- 6244737 TI - Lysis of infected myofibers by coxsackievirus B-3-immune T lymphocytes. AB - Spleen cells from male adult BALB/c mice given intraperitoneal injections of purified coxsackievirus B-3 were examined for the ability to lyse syngeneic neonatal myofibers in culture. Cytotoxicity against infected and uninfected targets was measured with the use of an in vitro 51Cr release assay. Immune spleen cells obtained 4--7 days after infection were cytotoxic for viral-infected myofibers. Peak reactivity was observed 5 days after infection. At this time immune spleen cells showed significantly less reactivity against uninfected myofibers. Cytotoxicity against infected targets was mediated by T lymphocytes, since reactivity was abolished by treatment with anti-thy 1.2 and complement. Treatment with anti-Ig and complement caused no loss of activity. Reciprocal assays performed with BALB/c and CBA cells showed that maximal cytotoxicity occurred against infected syngeneic myofibers, providing further evidence that viral-specific effector cells were T lymphocytes. In addition, hyperimmune rabbit anti-coxsackievirus B-3 antiserum could not block immune spleen cell lysis of infected targets, suggesting that coxsackievirus-infected myofibers expressed surface membrane antigens not recognized by specific neutralizing antibody. PMID- 6244738 TI - Animal model of human disease: leukemic lymphoma. PMID- 6244739 TI - Adrenocorticotropic hormone cells and immunoreactive beta-endorphin cells in the human pituitary gland: normal and pathologic conditions studied by the peroxidase labeled antibody method. AB - The comparative immunohistochemical localization of adrenocorticotropic hormone (ACTH) and beta-endorphin-like immunoreactivity (referred to as beta-endorphin) was studied in 16 human anterior pituitary glands from 6 normal adults, 4 normal fetuses, 1 stillborn infant, 2 anencephalic infants, 1 adult with Crooke's hyaline degeneration, and 2 patients with pituitary adenomas associated with Cushing's syndrome. Mirror sections were used in order to enable precise comparison of the same cells on the two consecutive tissue sections. In these normal and pathologic human anterior pituitary glands, ACTH and beta-endorphin were mostly localized in the same cells. In the normal adult pituitary glands, however, some ACTH cells were negative for beta-endorphin; and in one of the pituitary adenomas, some tumor cells were positive for only one hormone (beta endorphin). These data suggest concomitant production of ACTH and beta-endorphin in the same cells and support the production of precursor molecules for these two hormones. The significance of ACTH-positive, beta-endorphin-negative normal cells and beta-endorphin-positive, ACTH-negative tumor cells is also discussed. PMID- 6244741 TI - Effect of vitamin A on the hypothalamo-pituitary-thyroid axis. AB - This study reports the effects of the administration of pharmacologic doses of vitamin A on multiple parameters of thyroid function. Vitamin A decreased total T4 and T3 levels. With vitamin A treatment, there was a marked increase in the percentage dialyzable T3 and T4 both in vivo and in vitro. The serum-free T3 and T4 levels as measured by dialysis were on the whole normal in vitamin A-treated rats. Following thyroidectomy, the total T4 levels were still decreased, suggesting that vitamin A produced its effects by increasing peripheral clearance of thyroxine. Vitamin A did not alter basal thyroid stimulating hormone (TSH) or its response to thyroid releasing hormone, suggesting a relatively normal hypothalamic-pituitary-thyroid axis in vitamin A-treated animals. Vitamin A may decrease tissue responsiveness to thyroid hormones as evidenced by the tendency to decreased Na-K-ATPase activity in the livers from vitamin A-treated rats and the decreased growth hormone response to T3 in GH3 pituitary cultures as shown in this study and by the decreased basal metabolic rate found after vitamin A in previous studies. Vitamin A decreased thyroid gland size and increases 125I thyroid uptake. In vitro, vitamin A enhanced T4 to T3 conversion in hepatic homogenates. PMID- 6244740 TI - The sequential analysis of liver cell necrosis: inhibition of diethylnitrosamine- and dimethylnitrosamine-induced acute liver cell death by posttreatment with diethyldithiocarbamate. AB - Posttreatment with diethyldithiocarbamate (DEDTC) largely prevented the development of acute hepatocellular necrosis induced by diethylnitrosamine (DEN) and dimethylnitrosamine (DMN) in male Fischer rats as monitored by the release of glutamate-pyruvate transaminase and sorbitol dehydrogenase into the serum and by histologic examination. Liver cell necrosis was evident with a dose of 25 mg of DEN/kg and was progressive with increasing doses of DEN. DEDTC (50 mg/kg; three times at 4-hour intervals) was given at 4 or 8 hours after the administration of DEN (100 mg/kg), time points at which at least 50% and 75%, respectively, of the administered DEN had disappeared from both the serum and liver. Under these conditions, DEDTC prevented liver cell necrosis, except for a few isolated cells. Similar inhibition was also observed when DEDTC was given 4 hours after the administration of a necrogenic dose of DMN (20 mg/kg). DEDTC, when administered 4 hours after DEN, delayed the rate of clearance of DEN and of ethylation of DNA and RNA but did not significantly affect the total extent of ethylation of rat liver nucleic acids. These results offer further support for the multistep hypothesis for the development of liver cell necrosis. PMID- 6244742 TI - Isolation of epithelial cells from toad bladder. AB - The epithelial cells of the toad bladder have been isolated by brief exposure to ethylenediaminetetraacetic acid followed by treatment with collagenase, DNAse, and the application of shearing forces. This approach eliminates the need for scraping of the mucosal surface and reduces mechanical damage during harvesting of the epithelium. The method yields intact, isolated epithelial cells and few clumps. The three major types of epithelial cells described in the intact toad bladder were present in the final preparation. The cellular contents of nucleic acids and proteins (in pg/cell) were: DNA 22.5 +/- 1.1; RNA, 12.9 +/- 0.6; and protein, 192 +/- 9. The isolated cells possess rates of oxygen consumption and amino acid incorporation higher than those of epithelial sheets obtained by collagenase treatment and scraping of the intact bladder. However, the production of cyclic nucleotides in response to stimulation by vasopressin and carbachol is comparable in both preparations. PMID- 6244743 TI - Effect of glucagon on bile cAMP secretion. AB - The effect of bile flow and adenosine 3',5'-cyclic monophosphate (cAMP) secretion of substances that alter cAMP metabolism in other systems was evaluated. The experiments were performed on awake dogs with chronic biliary and gastric fistulas and on anesthetized rabbits prepared with acute bile fistulas. In all experiments the enterohepatic circulation was maintained by intravenous bile salt administration. In dogs, glucagon increased bile flow and bile cAMP secretion with 4 micrograms . kg-1 . h-1 increasing bile flow from control values of 273 +/ 27 to 413 +/- 6 microliters/min, whereas bile cAMP concentration rose from 3.9 +/- 0.9 to 12.1 +/- 1.1 nmol/ml. Theophylline in dogs increased bile flow while cAMP secretion decreased. Evaluation of the effects of theophylline on glucagon stimulated bile flow suggest that both agents act by the same mechanism; however, theophylline did not significantly alter glucagon-stimulated increases in bile cAMP. In rabbits, glucagon increased bile cAMP secretion while bile flow was not significantly changed. Hormonal production of increased systemic or hepatic cAMP can increase bile cAMP unassociated with changes in bile flow. Based on the measurement of cAMP in bile the increase in glucagon-stimulated bile flow produced by theophylline is not cAMP mediated. PMID- 6244745 TI - Mullerian tumors of uterus. PMID- 6244746 TI - Malignant mixed mesodermal tumors of the ovary: a clinicopathologic assessment of 12 cases. AB - Twelve women with mixed mesodermal tumors of the ovary were studied. These tumors grow rapidly and patients are frequently in an advanced state of their disease when the diagnosis is made. In 10 individuals the initial complaint was either an abdominal mass or increasing abdominal girth. With one exception, the patients were postmenopausal. The most important prognostic criterion was the stage of the tumor at the time of the diagnosis. Of nine women with Stage III and IV disease, only one is well and free of disease. No pathologic features were uncovered which could be related to prognosis. PMID- 6244744 TI - Mucosal gastrin receptor. III. Regulation by gastrin. AB - Specific binding of 125I-labeled gastrin to rat gastric mucosal membranes was found to vary with serum gastrin levels. The dissociation equilibrium constants were not significantly different between receptor preparations. However, the binding capacities of the membrane preparations were directly correlated with serum gastrin levels. Fasting, feeding a liquid diet, and antrectomy significantly decreased serum gastrin and the concentrations of the gastrin receptor. Treatment of fasted and liquid-fed animals with pentagastrin prevented the decrease in receptors. Vagotomy increased both binding capacity and serum gastrin levels. These data indicate that gastrin stimulates the production of its own receptor. The upregulation of the gastrin receptor was evident if the binding capacity was expressed per milligram of protein, per microgram of DNA, or per amount of 125I-labeled choleragen bound to the same membrane preparation. This indicates that the biological response to gastrin is controlled in part by the regulation of the number of gastrin receptors present and that gastrin plays a role in this regulatory process. PMID- 6244747 TI - Gestational and nongestational trophoblastic neoplasia: a historic and pathobiologic survey. AB - A peculiar fascination has existed with trophoblastic neoplasia as an entity from the earliest cognitive periods. An intensive level of controversy surrounded the question of histogenesis which was finally settled in the closing years of the 19th century as a neoplasm of fetally derived structures. It was appreciated that similar appearing tumors occurred in extrauterine sites and that males were also affected. The totipotential germ cell was suspected as the progenitor of these neoplasms. The purpose of this report is to review some of the milestone developments in our knowledge of gestational and nongestational trophoblastic tumors. In addition, the clinicopathologic features of these tumors and some problems in differential diagnosis are examined in the light of today's chemotherapeutic approach. PMID- 6244748 TI - Minimal breast carcinoma. AB - Fifty-three patients with intraductal and microinvasive carcinoma of the breast were analyzed. Comparison of two groups of patients, one treated before 1969 and the other since, revealed a decrease in the mean age from 50 to 44 years, an increase in the annual rate from 0.6 to 5.0 percent and an increase in bilateral disease from 0 to 40 percent. The study also showed that patients with microinvasive disease (invasion up to 0.5 cm) had the same excellent prognosis as those with intraductal cancer. The results of this study suggest that (1) simultaneous random mirror-image biopsies of the contralateral breast should be performed with intraductal cancer of the breast, and (2) total mastectomy with lymph node sampling is the maximal treatment necessary in both intraductal and microinvasive cancer of the breast. PMID- 6244749 TI - Hepatic resection for malignant tumors of the liver: essentials for a unified surgical approach. AB - A unified surgical approach to hepatic resection and a simplified terminology in the classification of hepatic resections are presented based on experience with several hundred hepatic resections using specially designed instruments. PMID- 6244750 TI - Metastatic glucagonoma. improvement after surgical debulking. AB - A patient with the classic manifestations of the glucagonoma syndrome and hepatic metastases is presented. Clinical improvement occurred after removal of the primary tumor by distal pancreatectomy and splenectomy. No further antitumor therapy has been needed over a 15 month postoperative follow-up despite metastatic disease. PMID- 6244752 TI - A procedure for the isolation and purification of plasmid DNA from Rhizobium meliloti. PMID- 6244751 TI - Recognition of adrenal insufficiency in the postoperative patient. AB - The signs and symptoms of adrenal insufficiency in the postoperative patient are generally nonspecific, and the diagnosis is usually made at postmortem examination. Two patients in whom adrenal insufficiency developed in the postoperative period are reported on (one had metastatic carcinoma to the adrenal glands and in the other bilateral adrenal hemorrhage developed during anticoagulant treatment). Both patients survived multiple, successive stressful episodes before the diagnosis of adrenal insufficiency was established by the alpha1-24 corticotropin stimulation test. PMID- 6244753 TI - A rapid, sensitive assay for starch phosphorylase and ADPglucose pyrophosphorylase. PMID- 6244754 TI - Amino acid composition of proteins eluted from polyacrylamide gels: background considerations. PMID- 6244755 TI - A spectrophotometric method for the determination of glucose-6-phosphatase activity. PMID- 6244756 TI - Recovery of DNA segments from agarose gels. PMID- 6244757 TI - An assay for thyroid hormone binding to chromatin receptors. PMID- 6244758 TI - Further purification of adenosine kinase from rat heart using affinity and ion exchange chromatography. PMID- 6244759 TI - Acute systemic anaphylaxis in adult domestic fowl: evidence for the protective role of H2-histaminergic and beta 2-adrenergic receptors. AB - Pentobarbital-anesthetized and spontaneously breathing, bovine albumin (BA) sensitized adult domestic fowl showed acute systemic anaphylaxis to IV injection of antigen (BA), which was characterized by arterial hypotension, central venous hypertension, and bradycardia. Large doses of pyrilamine maleate (/1-receptor antagonist) partially inhibited acute systemic anaphylaxis. On the other hand, metiamide (a specific H2-antagonist) and propranolol (beta-adrenergic antagonist) markedly enhanced the anaphylactic response. Terbutaline (beta 2-agonist), dimaprit (a highly selective H2-agonist), and compound FPL 55712 (a slow-reacting substance of anaphylaxis receptor antagonist) either significantly inhibited or reversed the anaphylactic response. Cimetidine (a newer H2-antagonist) enhanced only central venous pressor response to BA. This investigation appears to suggest a minor role of histamine and a major role of slow-reacting substance of anaphylaxis as chemical mediatiors of anaphylaxis. A protective role of beta 2 adrenergic and H2-histaminergic receptors seem to operate in immediate hypersensitivity reactions in adult domestic fowl. PMID- 6244760 TI - Clearance and shedding of infectious bovine rhinotracheitis virus from the nasal mucosa of immune and nonimmune calves. AB - Infectious bovine rhinotracheitis virus was rapidly cleared from the nasal mucosa of calves after intranasal aerosol exposure. Nonimmune calves (experiment 1) cleared 10(9) plaque-forming units (PFU) of virus from the nasal mucosa in less than 4 hours and 10(6) PFU of virus in 1 hour. An eclipse phase followed the clearance of viral inoculum. Replicating virus was first detected at 9 hours. Viral titers increased stepwise until maximum was attained on postinoculation day 4. Virus persisted in the nasal mucus until day 12. Clinical signs of disease corresponded with the shedding of virus. In contrast to nonimmune calves, immune calves (experiment 2; same calves as in experiment 1, but 30 days after initial exposure) cleared 10(9) PFU of virus in 1 hour and 10(6) PFU of virus in less than 5 minutes. An abortive reinfection occurred after exposure of immune calves with 10(9) PFU of virus. Virus was first detected in these calves at 14 hours after exposure and was not detected beyond 24 hours after inoculation. Immune calves given 10(6) PFU of virus did not shed virus after clearance of inoculum. Clinical signs of infection were not observed in immune calves after viral challenge exposure. The date indicated that there was no detectable residual virus beyond 3 hours after the exposure. PMID- 6244761 TI - Detection of antibody against transmissible gastroenteritis virus of pigs by indirect immunoperoxidase antibody test. AB - Immunoperoxidase intibody (IPA) test was developed for detecting antibody against transmissible gastroenteritis (TGE) virus of pigs. The IPA antibody titers in sera collected in the field from 82 pigs were approximately seven times higher than those obtained in a serum-neutralization test. The correlation between the TGE antibody concentrations in the IPA and serum neutralization tests was positive (r = +0.74). The IPA tests appears to have the potential for routine laboratory use for serologic diagnosis of TGE. PMID- 6244762 TI - Direct immunoelectron microscopy of transmissible gastroenteritis virus with immunoglobulins G and A and guinea pig complement. AB - Porcine colostral immunoglobulin (Ig)G and IgA, isolated from transmissible gastroenteritis virus-infected sows, were compared by direct immunoelectron microscopy. It was estimated, using antibodies with a less than a twofold difference in virus-neutralizing activity, that IgG was 500 times more efficient than was IgA for coating transmissible gastroenteritis virions. Guinea pig complement enhanced the antibody coating with IgG, but did not increase virus neutralizing activity of IgG or IgA. PMID- 6244763 TI - Enzootic bovine leukosis: prevalence of blood lymphocyte nuclear pockets in dairy bulls in the United States and foreign countries. AB - Studies of the incidence of enzootic bovine leukosis-related blood lymphlymphocyte nuclear pockets (LNP) were made of 743 dairy breed bulls in the United States and foreign countries. Statistical evaluation disclosed that the prevalence of these anomalous nuclear forms in the studs observed is significantly greater in the United States than in other countries. In particular, the average percentage of LNP-containing cells in each United States stud is estimated to be more than twice the level found in all but two non-United States studs studied and more than three times the level in the majority (10 of 19) of them. Moreover, United States studs exhibited a higher proportion of LNP suspicious and -positive cases than almost all of the non-United States studs. We believe this is valid evidence that serves to reinforce the expressed need for a federal surveillance program for enzootic bovine leukosis in the United States. PMID- 6244764 TI - Porcine rotaviral infection of cell culture: effects of certain enzymes. AB - Porcine rotaviral infectivity for continuous porcine kidney (PK-15) cells was enhanced by incorporation of pancreatic endopeptidases into the cell culture maintenance medium. Marked enhancement of infectivity was induced by trypsin, whereas elestase and alpha-chymotrypsin enhanced infectivity to a lesser extent. Bacterial protease also induced some enhancement of porcine rotaviral infectivity. A synergistic enhancement of porcine rotaviral infectivity was noticed with trypsin and alpha-chymotrypsin combined. Porcine rotaviral infectivity was not affected by incorporation of alpha-amylase, alkaline phosphatase, beta-galactosidase, carboxypeptidase-A, deoxyribonuclease, enterokinase, lipase, or ribonuclease into the maintenance medium. PMID- 6244765 TI - Identification of rotaviruses of different origins by the plaque-reduction test. AB - The plaque assay for the simian rotavirus SA11 was shown to be applicable to the economically important calf and porcine rotaviruses. In addition, neutralization of viral infectivity with specific antiserum before assay (plaque-reduction test) was found to be a useful test to identify the species of origin of rotaviruses. PMID- 6244766 TI - Association of viral and Mycoplasma pneumoniae infections with acute respiratory illness in patients with chronic obstructive pulmonary diseases. AB - The relative importance of respiratory virus and M. pneumoniae infections as causes of acute respiratory illnesses was studied over an 8 yr period in 150 subjects who were normal or who had varying degrees of chronic obstructive pulmonary disease (COPD). Viral or M. pneumoniae infections were associated with 186 of 1,030 (18%) illnesses studied, whereas these infections were detected in only 86 of 1,398 (6%) illness-free periods (P less than 0.01). Rhinoviruses, influenza viruses, parainfluenza viruses and coronaviruses were each significantly associated with acute respiratory illnesses. The occurrence of acute respiratory illnesses and viral infections was the same in subjects with moderate to severe COPD as it was in subjects who were normal or who had mild disease. PMID- 6244767 TI - Effect of acute lung injury on angiotensin converting enzyme in serum, lung lavage, and effusate. AB - The administration of an acute pulmonary edemagenic dose (ip) of thiourea to rats results in an elevation of angiotensin converting enzyme (ACE) in serum, lung lavage, and pleural effusion. The increased serum ACE corresponds to a reduction in lung ACE, but it is transient, lasting between 1 and 2 h. ACE remains elevated in lung lavage and pleural effusion for at least 4 h after the administration of thiourea. PMID- 6244768 TI - Calcium and phosphate metabolism in tumoral calcinosis. AB - We have recently seen a patient with tumoral calcinosis, a syndrome comprising hyperphosphatemia, normocalcemia, normal glomerular filtration rate (GFR), and extensive periarticular calcific masses. Parathyroid hormone (PTH) deficiency or target organ resistance was ruled out by demonstration of normal serum PTH and urinary 3'5'cyclic AMP excretion and normal response to exogenous PTH and to endogenous stimulation by ethylenediaminetetraacetate. An intrinsic proximal tubular defect allowing enhanced renal PO4 reabsorption was probably present because there was no phosphaturic response to acetazolamine and renal PO4 threshold remained abnormally elevated even after PTH infusion. We then studied the mechanism by which serum calcium level is maintained in the normal range despite hyperphosphatemia and absence of secondary hyperparathyroidism. Normal 1,25-(OH)2 vitamin D was found, suggesting normal gastrointestinal calcium absorption. This, combined with markedly reduced urinary calcium excretion, perhaps a direct effect of hyperphosphatemia, may maintain calcium balance and prevent secondary hyperparathyroidism. A rise in urinary cyclic AMP excretion after furosemide-induced calciuria supports this hypothesis. PMID- 6244769 TI - Changes in the activity and isozyme patterns of glycolytic enzymes during stimulation of normal human lymphocytes with phytohaemagglutinin. AB - A study has been made of the effects of phytohaemagglutinin on the gene expression of the glycolytic enzymes in cultured human lymphocytes. All the enzymes were found to show an average increase in activity of between 160% and 360% in stimulated cells, but the increases were greater for the enzymes comprising the second half of the pathway. The enzyme activities in stimulated cells, cultured for 72 h, were similar to the activities measured in long-term lymphoid lines. Starch-gel electrophoresis was used to examine the isozyme patterns of the enzymes before and after exposure of the lymphocytes to PHA. Six of the enzymes showed isozyme patterns unchanged by stimulation. Four of the enzymes, aldolase, triosephosphate isomerase, enolase and lactate dehydrogenase, showed different isozyme patterns in stimulated cells from those seen in uncultured or unstimulated cells. The electrophoretic results showed a good correlation in isozyme pattern between uncultured lymphocytes and cultured unstimulated lymphocytes, and between PHA-stimulated lymphocytes and long-term lymphoid lines. PMID- 6244770 TI - Assignment of the human locus determining phosphoglycolate phosphatase (PGP) to chromosome 16. AB - The segregation of human phosphoglycolate phosphatase has been studied in 52 independent human-rodent hybrids and 69 subclones. The results suggest that human PGP is on chromosome 16. Family data suggest that PGP is not close to 16qh or alpha Hp. The most likely regional assignment for PGP would appear to be 16p13 or 16p12, but a site on 16q cannot be entirely excluded. New data on 16qh and alpha Hp suggest that the male recombination fraction between these loci is about 0.2. PMID- 6244771 TI - Pituitary adenomas: clinicopathological and immunohistochemical study. PMID- 6244772 TI - Cerebellar control of ocular gaze stability. AB - The ability to hold an eccentric position of gaze has been attributed to a brainstem network termed the ocular motor neural integrator. For this integrator to function properly, an intact cerebellum is necessary. This report describes a patient with cerebellar dysfunction who showed an unusual form of nystagmus: each slow phase had a waveform of increasing velocity. This contrasts with gaze paretic nystagmus, the more typical manifestation of cerebellar disorder, in which each slow phase has a waveform of decreasing velocity. Based on these observations and results from basic research, we propose that (1) the cerebellum controls neural integration in the brainstem by a positive feedback loop, and (2) pathological alterations in the strength of transmission (or gain) through the feedback loop cause the eyes to drift off target, with either an exponentially increasing (gain too high) or decreasing (gain too low) velocity. PMID- 6244773 TI - The carcinomatous neuromyopathy of oat cell lung cancer. AB - A prospective controlled clinical-neurophysiological-pathological study of 71 patients with oat cell carcinoma of the lung revealed no increased incidence of peripheral neuropathy at the initial stages of illness. All patients developed neuropathy by the time they had lost 15% of their body weight, but the neuropathy was less severe than in 20 age-matched alcoholic patients with an equal degree of weight loss. The weight loss and peripheral neuropathy progressed with atrophy of type II (adenosine triphosphatase-positive) muscle fibers out of proportion to the patient's loss of body weight. By 40% body weight loss, all the patients had moderate symmetrical peripheral neuropathy, 6 had proximal brachial or lumbosacral plexus metastases, and 9 had distal pressure palsies. Mononeuritis multiplex developed in only 1 patient, who had diabetes mellitus. Two patients developed Eaton-Lambert syndrome, which resolved in 1 when chemotherapy controlled the systemic tumor, with no protein in the tumor postmortem which could produce the characteristic electromyographic findings of the syndrome. PMID- 6244774 TI - Barognosis in a patient with hemiataxia. AB - Barognosis was tested in a patient who had a lesion of the right cerebellar hemisphere. While blindfolded, he used each hand to estimate the mass of given test loads, alternating hands between trials. He moved each load sinusoidally, comparing it with the previous one. The period of oscillation was found to be a linear function of the mass. With each load, the period of oscillation was longer when he used the ataxic hand. On 23 of 59 comparisons between loads, the patient reported incorrectly. Ninety-one percent of the errors were in the direction of loads feeling heavier when the ataxic hand was used. To explain these results, it is proposed that (1) the perceived magnitude of a load depends on the corollary discharge, and (2) cerebellar damage may reduce the accuracy of the corollary discharge. PMID- 6244775 TI - Variations in the levels of cyclic adenosine 3':5'-monophosphate and in the activities of adenylate cyclase and cyclic adenosine 3':5'-monophosphate phosphodiesterase during aerobic morphogenesis of Mucor rouxii. PMID- 6244776 TI - Further studies on cyclic adenosine 3':5'-monophosphate protein kinase from dimorphic fungus Mucor rouxii. PMID- 6244777 TI - Inhibitors of superoxide dismutases: a cautionary tale. PMID- 6244778 TI - A substance in L-929 cell extracts which replaces the ascorbate requirement for prolyl hydroxylase in a tritium release assay for reducing cofactor; correlation of its concentration with the extent of ascorbate-independent proline hydroxylation and the level of prolyl hydroxylase activity in these cells. PMID- 6244779 TI - Adenine nucleotide translocase as a site of regulation by ADP of the rat liver mitochondria permeability to H+ and K+ ions. PMID- 6244780 TI - Effect of incubation temperature on motility and cAMP content of bovine sperm. PMID- 6244781 TI - Kinetic identification of component X as P430: a primary electron acceptor of Photosystem I. PMID- 6244782 TI - Absorption spectra of mixed monomolecular films of chlorophyll and photosynthetic electron carriers at a gas-water interface. PMID- 6244783 TI - Studies on sphingomyelinase of Bacillus cereus: hydrolytic and hemolytic actions on erythrocyte membranes. PMID- 6244784 TI - Serine ethanolamine phosphate in avian muscular dystrophy: mechanism of accumulation in dystrophic muscle and relationship to phospholipid synthesis. PMID- 6244785 TI - Bovine prothrombin does not contain alpha-D-galactopyranosyl groups. PMID- 6244786 TI - Spin trapping of superoxide and hydroxyl radical: practical aspects. PMID- 6244787 TI - Interaction of melanin with oxygen. PMID- 6244788 TI - Nucleotides do not modulate rat luteocyte human chorionic gonadotropin responsiveness by inhibiting human chorionic gonadotropin binding. PMID- 6244789 TI - Spin label studies of microsomal membranes from Acanthamoeba castellanii in different states of differentiation. PMID- 6244790 TI - Asymmetric incorporation of Na+, K+-ATPase into phospholipid vesicles. PMID- 6244791 TI - Biosynthesis of polymyxin by Bacillus polymyxa. I. The status of the biosynthetic multienzyme complex during active antibiotic synthesis and sporulation. PMID- 6244792 TI - Biosynthesis of polymyxin by Bacillus polymyxa. II. On the nature and interaction of the multienzyme complex with the end product polymyxin. PMID- 6244793 TI - Sex steroid levels in serum, myometrium, and fibromyomata in correlation with cytoplasmic receptors and 17 beta-HSD activity in different age-groups and phases of the menstrual cycle. PMID- 6244794 TI - [Inhibition of implantation in the rat due to bromocriptine (author's transl)]. AB - The increase in the number of the ovarian LH/HCG-receptors and the rise in serum progesterone concentration during pregnancy in the rat depend on the presence of prolactin during the process of luteinization. Blocking of the hypophyseal prolactin secretion in rats by twice daily injections of 2 micrograms/g of body weight of bromocriptine from the first day of pregnancy onwards prevents the increase in ovarian HCG-binding, progesterone production, and the implantation of blastocysts. The lack of implantation is not due to a teratogenic effect of bromocriptine but is due to deficient decidual changes caused by a lack of progesterone production by luteal cells. PMID- 6244796 TI - Effect of cyproterone acetate on structure of adrenal cortex in hypophysectomized, ACTH treated mice. AB - Hypophysectomized adult male C57BL/6J mice injected with 0.08 mg/g of cyproterone acetate showed large aggregates of cellular lipid as well as nodular formations in the zona fasciculata of the adrenal cortex. Daily ACTH injections (10 IU) reversed the atrophic changes noted above. At the ultrastructural level, the zona fasciculata and zona reticularis cells exhibited decreased cellular lipid content, proliferated profiles of rough endoplasmic reticulum, an increase in polyribosomes, and an active Golgi apparatus. It is believed that cyproterone acetate inhibited adrenocortical steroidogenesis by interfering with pituitary release of ACTH. PMID- 6244795 TI - Hyperinsulinemic hypoglycemia of the neonate associated with persistent fetal histology and function of the pancreas. AB - Early in development, the fetal pancreas is characterized by the presence of two distinct generations of endocrine cells and a B-Cell mass that is unresponsive to acute changes in circulating glucose levels. Near the end of intrauterine development, the normal pancreas has "matured" and contains a single generation of endocrine cells and B-Cells that are responsive to changes in glucose concentrations. Recent microscopic examination of resected pancreatic tissue from an infant with hyperinsulinemic hypoglycermia revealed a combination of all three of the currently accepted findings in this neonatal condition: hyperplasia, adenomatosis, and nesidioblastosis. These observations prompted the following hypothesis: When compared to the usual histology of the developing pancreas, nesidioblastosis may be interpreted as an abnormal continuation of normal proliferation of endocrine cells; hyperplasia may be a specific overproduction of the Secondary Islands of Langerhans; and adenomatosis may be an abnormal continuation or overgrowth of the Primary Island of Langerhans. Such extrapolation suggests that infants with hyperinsulinemic hypoglycemia may represent a failure in the normal histological and functional maturation of the endocrine portion of the fetal pancreas. PMID- 6244797 TI - DNase II in bull and ram sperm tail and mitochondria. AB - Extracts of bull and ram sperm tails were prepared by DTT and CTAB treatment. Such extracts contained deoxyribonuclease II, degrading only native double stranded DNA at acid pH (3.9--4.5). At least three distinguishable DNase II activities were found in these extracts as judged by their sensitivity to thiol compounds and various anions and cations. The deoxyribonuclease II activity is apparently located in or in association with the mitochondria. PMID- 6244798 TI - Synovial fluid leukocytosis associated with intracellular lipid inclusions. AB - A unique case of an inflammatory monoarthritis associated with intracellular lipid inclusions in synovial fluid leukocytes is described. In contrast to previous reports, these lipid inclusions were uniformly intracellar, not associated with articular destruction, and not visible under ordinary light but readily seen under polarized light microscopy. PMID- 6244799 TI - Hypoglycemia in pregnancy. Occurrence due to adrenocorticotropic hormone and growth hormone deficiency. AB - Severe symptomatic hypoglycemia (serum glucose level, 24 mg/dL) developed in a 23 year-old, 147.3-cm-tall woman during her late second and third trimesters of pregnancy. Endocrine studies disclosed insulin levels less than 2 microU/mL; growth hormone level less than 3 ng/mL; and cortisol level less than 1 microgram/dL. Hydrocortisone therapy corrected her hypoglycemia, and she was delivered of a healthy female infant. Postpartum, her evaluation included normal thyroid function studies, a normal thyroid-stimulating hormone response to protirelin (thyrotropin-releasing hormone), normal serum and urine gonadotropin levels, normal serum prolactin, normal sella turcica tomograms, and a normal EMI brain scan. Urine 17-hydroxycorticosteroids increased during a four-day cosyntropin infusion, but failed to rise after metyrapone administration. The growth hormone level failed to rise after stimulation with levodopa and propranolol administration. The patient was believed to have idiopathic partial hypopituitarism, with hypoglycemia being due to adrenocorticotropic hormone (ACTH) and growth hormone deficiency and the drain of maternal glucose by the fetus. It is suggested that pregnant women with symptomatic hypoglycemia be treated with glucocorticoids while awaiting the results of their endocrine evaluation. PMID- 6244800 TI - Cytomegalovirus infection. PMID- 6244801 TI - Spondyloepiphyseal dysplasia congenita. A comparative study of chondrocytic inclusions. AB - Spondyloepiphyseal dysplasia congenita is a short-trunk chondrodysplasia trait. The abnormalities are present at birth and involve primarily the spine, the epiphyses of long bones, and the pelvis. Postmortem examinations of two patients with this disease who died shortly after birth showed a mild disorganization of chondrocytic columnization in the physeal growth zone. The chondrocytes contained PAS-positive cytoplasmic inclusions after diastase digestion to eliminate glycogen. Ultrastructural examination of the inclusions in one patient showed them to be accumulations of finely granular material in dilated cisterns of rough endoplasmic reticulum. To our knowledge, similar findings have been seen only in three other types of chondrodysplasia. The inclusions, which therefore are of diagnostic importance, may be of importance also in reflecting the primary metabolic abnormality. PMID- 6244803 TI - [Experimental models of embryonic nephroblastomas (Wilms' tumor)]. AB - Histological structure and histochemical characteristics of renal tumours induced in rats either by N-nitrosodimethylamine (DMNA) or N-nitrosoethylurea (NEU) are described. The rats treated with oral administration of DMNA developed 1 nephroblastoma and 176 mesenchymal tumours similar to mesoblastic nephroma. In rats receiving the transplacental treatment with NEU 24 mesenchymal tumours and 5 nephroblastomas corresponding to the epithelial variant of human Wilms' tumour occurred. Histologic and histochemical findings show that the mesenchymal neoplasms contain the epithelial component in the form of preexisting renal tubules. These tubules are similar to those of the normal kidney and strongly differ from the primitive tubular structures of embryonic rat kidneys and nephroblastomas. PMID- 6244802 TI - [ATPase and 5-nucleotidase in human breast and stomach tumors]. AB - It has been concluded from the studies on the activity and location of ATPase and 5-nucleotidase in mammary and gastric tumours that some neoplasms of the mammary gland and stomach showing a high ATPase activity are histochemically related, in the former case, to the lobular myoepithelium and in the latter case, to non differentiated cells of gastric glands which acquired a capacity for intestinal metaplasia and preserved it in the course of malignant transformation. No essential changes have been recorded in the activity of 5-nucleotidase, depending on the tumour histologic structure and degree of its maturity. PMID- 6244804 TI - Cytomegalovirus and dual infection in infants. AB - In four unrelated infants without underlying immunodeficiency, dual infections with cytomegalovirus (CMV) and another microorganism developed. The patients included the following: (1) a 3-month-old girl with congenital CMV and perinatal cutaneous herpes simplex virus; (2) a 5-week-old girl with CMV and Pneumocystis carinii; (3) a 12-week-old girl with CMV and Haemophilus influenzae meningitis; and, (4) a 2 1/2-month-old girl with CMV and Escherichia coli meningitis. In all four cases, the patient's initial symptoms were referable not to CMV, but to the companion infecting organism. The diagnoses of CMV infection were made, respectively, by a high index of clinical suspicion in the first three cases and on the basis of a lucent parenchymal defect on computerized tomographic scan in the fourth patient. These cases provide additional evidence that CMV infection may predispose to secondary infection. We recommend that infants who have signs of infection and evidence of CNS abnormalities have cultures made for CMV. Both human CMV and experimental murine CMV infections have been associated with suppressed cellular and possibly humoral immunity. PMID- 6244805 TI - Pathogenesis of varicella-zoster angiitis in the CNS. AB - A 20-year-old man with Hodgkin's disease experienced ophthalmic zoster with dissemination and CNS involvement. At autopsy, he was found to have granulomatous angiitis involving the basilar artery, and electron microscopy revealed virus like particles in the outer layers of the vessel walls, but not the endothelium. This suggests that granulomatous angiitis of the CNS in varicella-zoster infections results from direct viral invasion of blood vessels, perhaps by contiguous spread from cranial nerves. PMID- 6244806 TI - Amyloid neuropathy and tremor in Waldenstrom's macroglobulinemia. AB - We report a case of Waldenstrom's macroglobulinemia with amyloid neuropathy and a parkinsonian syndrome. We describe the light and electron microscopic findings in a sural nerve biopsy specimen and discuss the possible pathogenic mechanisms in the production of the neuropathy. In contrast to a number of previous cases of neuropathy associated with Waldenstrom's macroglobulinemia, evidence of immunoglobulin deposition on nerve fibers was not found using immunofluorescent techniques. PMID- 6244807 TI - Detecting DNA in herpes simplex virus. PMID- 6244808 TI - Treatment of experimental herpetic interstitial keratitis with medroxyprogesterone. AB - A model of herpes simplex interstitial keratitis was developed in rabbits sensitized with live herpes simplex virus (HSV) type 2 and challenged intrastromally with live virus. This model was used to evaluate the effects of subconjunctival medroxyprogesterone acetate on the course of the disease and on collagenase levels in the treated corneas. Whether treated prophylactically or therapeutically, the medroxyprogesterone-treated groups had substantially less stromal infiltration and neovascularization than the controls. The clinical effects corresponded with a marked reduction in the polymorphonuclear leukocyte infiltrate histologically, and the suppression of latent and active collagenase activity in the treated corneas cultured in vitro. However, epithelial disease was exacerbated in prophylactically treated animals. Medroxyprogesterone appears to be useful in the treatment of herpetic interstitial keratitis as an anti inflammatory agent as well as an inhibitor of collagenase production but, like the corticosteroids, it can exacerbate epithelial disease. PMID- 6244809 TI - Structural features of extraocular muscles of children with strabismus. AB - Ninety extraocular muscle (EOM) biopsy specimens from 80 children with strabismus and normal ocular alignment were studied by light microscopy, enzyme histochemistry, and electron microscopy. Light microscopy showed considerable variation in muscle fiber shape and size with sarcomere disruption, sharp increases in endomysial and perimysial collagen, numerous vacuoles and subsarcolemmal inclusions. Electron microscopy showed disruption of myofilaments, nemaline rods, abnormal mitochondria, leptomeric profiles, occasional "myelin figures," glycogen, and lipid-like droplets. Some intramuscular nerves contained long-spacing collagen ("Luse bodies"). Unlike somatic skeletal muscle, EOM showed a consistent lack of mosaic pattern and reciprocal stain activity between fiber types noted by enzyme histochemistry. Quantitative observations indicate that minimal but consistent morphologic differences exist between strabismic and nonstrabismic EOM. The role these changes play in the pathogenesis of strabismus and their significance remains unclear. PMID- 6244810 TI - Neurotologic manifestations of the osteopetroses. AB - Facial nerve paralysis or symptoms of audiovestibular nerve dysfunction may be the first indication of one of the group of bone diseases known as the osteopetroses. We describe three such patients. The pathophysiology of these diseases and the treatment of the resulting symptoms of facial and audiovestibular nerve dysfunction are discussed. PMID- 6244811 TI - The nasopharyngeal angiofibroma. AB - Between 1948 and 1975, we have seen 48 patients with nasopharyngeal angiofibroma. Radiotherapy is the treatment of choice for most patients. A dose of 3,000 rads in three weeks leads to thrombosis, fibrosis, and tumor regression, although a latent period up to two years may elapse before final disappearance. Coronal tomography demonstrated tumor extension into the accessory air sinuses in 26 of 29 patients examined. Radiation controlled the tumor both clinically and radiologically from two to 20 years in 28 (80%) of 35 patients treated for the first time. Ten patients, initially treated by surgery, underwent irradiation for recurrence, and in seven the tumor was controlled. Overall, ten (22%) of 45 tumors were not controlled by the first course of radiotherapy; seven of these were controlled by a second course and three were treated by surgery. Hormonal study results on 12 patients were normal. PMID- 6244812 TI - Extramammary cystosarcoma phyllodes with bilateral breast involvement. AB - A 30-year-old woman presented with breast masses. One of the breast masses was clinically suggestive of cystosarcoma phyllodes. Excision of the breast masses revealed bilateral cystosarcoma phyllodes. A few weeks later another lump appeared in the left groin, and this on excision was found to be cystosarcoma phyllodes at an aberrant site. We consider it a unique clinical presentation of cystosarcoma phyllodes. PMID- 6244813 TI - Cytochrome oxidase from an extreme thermophile. Thermus thermophilus HB8. PMID- 6244814 TI - Lithium on glucose uptake in brain; role of glucose-1,6-P2 as a regulator of hexokinase. PMID- 6244815 TI - Partial N-terminal amino acid sequence of pro-opio-melanocortin (ACTH/beta-LPH precursor) from rat pars intermedia. PMID- 6244816 TI - Increase of asparagine-linked oligosaccharides with branched outer chains caused by cell transformation. PMID- 6244817 TI - Binding of cytochrome c to cytochrome c-oxidase in intact mitochondria. A study with radioactive photoaffinity-labeled cytochrome c. PMID- 6244818 TI - Interaction of polyriboinosinic acid, polyribocytidylic acid with human lymphoblastoid cells. PMID- 6244819 TI - Hormone-induced desensitization of cultured rat granulosa cells to FSH. PMID- 6244820 TI - Hormonal control of phenylalanine hydroxylase activity in isolated rat hepatocytes. PMID- 6244821 TI - Leukotriene A: stereochemistry and enzymatic conversion to leukotriene B. PMID- 6244822 TI - A cobalt containing protein isolated from Desulfovibrio gigas, a sulfate reducer. PMID- 6244823 TI - Effect of histamine on adenosine 3',5'-cyclic monophosphate levels in granulation tissue. PMID- 6244824 TI - The effect of desipramine on the noradrenaline stimulated Na-K ATPase of rabbit synaptic membranes. PMID- 6244825 TI - Quantitative structure-activity relationships for the inhibition of heart and brain cyclic AMP phosphodiesterases by some phenylbutenolides. PMID- 6244826 TI - 3,4-dihydroxyphenylacetic acid content of sympathetic ganglia as a possible biochemical indicator of small intensely fluorescent cell participation in ganglionic transmission. PMID- 6244827 TI - Inhibitory characteristics of the mycotoxin penicillic acid on (Na+-K+)-activated adenosine triphosphatase. PMID- 6244828 TI - Effects of alamethicin on hormonal activation of renal adenylate cyclase. PMID- 6244829 TI - Opiate-like effects of norlaudanosolinecarboxylic acids on the hypothalamic pituitary-gonadal axis. PMID- 6244830 TI - Effect of some drugs on thromboplastin (factor III) activity of human monocytes in vitro. PMID- 6244831 TI - Identification of a beta 2-adrenergic receptor in mammalian epidermis. PMID- 6244833 TI - Interactions of D600 (methoxyverapamil) and local anesthetics with rat brain alpha-adrenergic and muscarinic receptors. PMID- 6244832 TI - The effects of cadmium, manganese and aluminium on sodium-potassium-activated and magnesium-activated adenosine triphosphatase activity and choline uptake in rat brain synaptosomes. PMID- 6244835 TI - Prenatal induction of Na,K-stimulated adenosine 5'-triphosphatase activity in hamster intestine. PMID- 6244834 TI - Inhibition by methylmercuric chloride of prostaglandin E1-sensitive adenylate cyclase activity in glioma but not in neuroblastoma cells in culture. PMID- 6244836 TI - Modes of action of hypoxanthine, inosine and inosine 5'-monophosphate on cyclic nucleotide phosphodiesterase from bovine brain. PMID- 6244837 TI - Involvement of tropomyosin in the sensitivity of Na+ + K+ ATPase to ouabain. PMID- 6244838 TI - In vivo effects of apomorphine and 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (RO 20-1724) on cyclic nucleotides in rat brain and pituitary. PMID- 6244839 TI - Kinetic alterations in rat liver microsomal cholecalciferol 25-hydroxylase associated with phenobarbital administration. PMID- 6244840 TI - An assay for alpha-adrenergic receptor subtypes using [3H]dihydroergocryptine. PMID- 6244841 TI - Interaction of tricyclic antidepressants with opiate receptors. PMID- 6244842 TI - Neuromuscular pharmacology. A clinical update and commentary. PMID- 6244843 TI - Maturation of neuromuscular transmission in the infant. AB - Twitch tension, train-of-four and tetanus--clinical parameters of neuromuscular transmission--were studied in 37 infants and children anaesthetized with halothane. The contraction time was slower in infants less than 1 month old when compared with their elder counterparts. This may indicate a possible transformation from slow to faster muscle types. The train-of-four reached 100% in most of the infants older than 2 months. The post-tetanic facilitation and the tetanus : twitch ratios were significantly greater in infants older than 2 months when compared with infants less than 1 month. Post-tetanic exhaustion was seen in all the infants and children after stimulation at 100 Hz. Tetanus : twitch ratios were greater in infants more than 2 months old and in children, and the tetanic force was more marked at 50 Hz than at 20 Hz. The data indicate that maturation of neuromuscular transmission occurs in infants in and around the first 2 months of age. PMID- 6244844 TI - An unusual presentation of oat-cell carcinoma of the bronchus. PMID- 6244845 TI - Effect of prior inoculation with chemical carcinogens on development of avian retrovirus-induced neoplasia in chickens. PMID- 6244846 TI - Measurement of net proton-hydroxyl permeability of large unilamellar liposomes with the fluorescent pH probe, 9-aminoacridine. AB - The fluorescent probe 9-aminoacridine was used to measure the rate of decay of experimentally established pH gradients across liposome membranes. From the rate of decay, separate permeability coefficients for protons (PH) and hydroxyls (POH) were calculated and summed to yield the net proton-hydroxyl permeability (Pnet). The net permeability of protons and hydroxyls was found to be approximately 10( 4) cm/s, six orders of magnitude greater than that measured for sodium and pyrophosphate ions under similar conditions. This suggests that protons and/or hydroxyls cross lipid bilayers by a different mechanism than do other monovalent cations and anions. In addition, the measurements provide a standard for net proton-hydroxyl permeability in pure phospholipid bilayers for comparison with biological membranes. PMID- 6244847 TI - The prosthetic groups in succinate dehydrogenase. Number and stoichiometry. AB - I. Succinate:Q oxidoreductase (EC 1.3.99.1) as present in beef-heart submitochondrial particles contains equal amounts of FAD, a [2Fe-2S] cluster and a [4Fe-4S] cluster. Both Fe-S clusters are reducible by succinate. 2. A second type of [2Fe-2S] cluster, called center S-2, that has been proposed to be present in purified preparations of succinate dehydrogenase and isolated Complex II (Ohnishi, T., Winter, D.B., Lim, J. and King, T.E. (1973) Biochem. Biophys. Res. Commun. 53, 231--237) is an artifact introduced by the purification procedure. 3. It is suggested that the 70 000 dalton subunit which is known to bind the flavin, accomodates also the [4Fe-4S] cluster whereas the 28 000 dalton subunit contains the [2Fe-2S] cluster. PMID- 6244848 TI - The interaction of myeloperoxidase with ligands as studied by EPR. AB - 1. The reaction of myeloperoxidase with fluoride, chloride and azide has been studied by EPR. 2. Fluoride decreases the rhombicity of the high-spin heme signal of myeloperoxidase and the nuclear spin of the fluoride atom induces a splitting in g parallel of 35 G. This observation demonstrates that fluoride binds as an axial ligand to the heme iron of the enzyme. 3. Addition of chloride to the fluoride-treated enzyme increases the rhombicity of the high-spin heme signal and brings about a disappearance of the splitting at g parallel. The addition of azide to the fluoride-treated enzyme changes the spin state of the heme iron from a high-to a low-spin state (gx = 2.68, gy = 2.22 and gz = 1.80). 4. Upon addition of chloride or fluoride to low-spin azido-myeloperoxidase this compound is converted into the high-spin chlorido- or fluorido-myeloperoxidase. These observations demonstrate that these ligands compete for a binding site at or close to the heme iron of myeloperoxidase. PMID- 6244849 TI - Specific spin-labeling at trypsin active site. Application of 'inverse substrate' to the structural analysis of the active site. AB - Specific and reversible spin-labeling of trypsin (EC 3.4.21.4) active site was carried out by 'inverse substrate', 3-carboxy-2,2,5,5-tetramethyl-1 pyrrolidinyloxyl and 3-carboxy-2,2,5,5-tetramethyl-1-pyrrolinyloxyl-p amidinophenyl esters. The paramagnetic resonance spectra of the labeled trypsin in the form of acyl enzyme intermediate were investigated. The 2T value, separation of the outer hyperfine extrema, was observed to be sensitive to pH of the medium. These results are discussed in terms of pH-dependent conformational change at the vicinity of active site. PMID- 6244850 TI - Endogenous phosphorylation of soluble enzymes in human red cells. Cyclic 3',5' AMP-dependent phosphorylation of phosphofructokinase without detectable regulatory effect. AB - ATP-depleted human red cells have been incubated in a glucose-containing medium with [32P]orthophosphate in the presence and in the absence of cyclic 3',5'-AMP and dibutyril cyclic 3',5'-AMP. Spectrin, pyruvate kinase, phosphofructokinase, glucose-6-phosphate dehydrogenase and hemoglobin A1 have been purified and analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Protein bound radioactivity has been measured from the sodium dodecyl sulfate polyacrylamide gels and the trichloroacetic acid-precipitated proteins. In the cytosol, the most intense phosphorylation was found for pyruvate kinase whose, in the presence of cyclic AMP, specific radioactivity was comparable to that of the membrane protein and spectrin. In the absence of cyclic nucleotides it was five times less phosphorylated. Phosphofructokinase was only phosphorylated when the red cells were incubated with cyclic nucleotides; the extent of phosphorylation was four times less than for pyruvate kinase. Hemoglobin, glucose-6-phosphate dehydrogenase and a contaminant protein copurified with phosphofructokinase were not phosphorylated: the 'background' of the radioactivity found for these proteins was 100 times less than for pyruvate kinase and spectrin, and 20 times less than for phosphofructokinase (+cyclic AMP). PMID- 6244851 TI - A protease from rat intestine. AB - Partially purified ribonuclease H from rat liver nuclei can be inactivated by a soluble fraction from rat intestine; this inactivation is restored by adding trypsin inhibitor, suggesting that the factor is a protease. A preparation has been isolated and purified to homogeneity. The molecular weight of the enzyme was estimated as 28 000 with an optimum pH of 8.0 and an isoelectric point at pH 4.5- 4.7. The inactivating and proteolytic activities were observed in parallel throughout the purification procedures. Diisopropylphosphorofluoridate inhibited the protease activity. The protease inactivates deoxyribonuclease I, pyruvate kinase, and aldolase. From experiments with protease modifiers, it seems to be a serine protease of a trypsin-like nature. PMID- 6244852 TI - The crystallization of mitochondrial cytochrome oxidase-cytochrome c complex. AB - Conditions are described under which crystals are formed with equimolar complex of mitochondrial cytochrome oxidase and cytochrome c. Characteristic absorption bands of the solubilized crystals could be attributed to the cytochrome oxidase cytochrome c complex with heme a:c ratio of 2:1. Activity of crystals shows more close heme-heme interaction between two cytochromes than that of the mixture. PMID- 6244853 TI - ESR studies on oxidation state changes of copper in superoxide dismutase during reactions with water radiolysis products at cryogenic temperatures. AB - Irradiating the aqueous solutions of native and reduced superoxide dismutase with 60Co gamma-rays at 77 K and recording the ESR spectra during thermal annealing the formation and decay of the complexes E-Cu2+...HO2 and E-Cu+...HO2 have been observed. Decay of ESR signals corresponding to HO2 in these complexes is not accompanied by immediate changes of the oxidation state of copper. The delayed changes of copper oxidation state are probably due to the reactions of dismutation products with superoxide dismutase. PMID- 6244854 TI - Purification and characterization of adenylate kinase isozymes from rat muscle and liver. AB - Isozymes of adenylate kinase (ATP:AMP phosphotransferase, EC 2.7.4.3) were purified from skeletal muscle and liver of rats to essentially homogeneous states by acrylamide gel electrophoresis and sodium dodecyl sulfate gel electrophoresis. The isozyme from muscle was purified by acidification to pH 5.0, and column chromatography on phosphocellulose, Sephadex G-75 and Blue Sepharose CL-6B, while that from liver was purified by column chromatography on Blue Sepharose CL-6B, Sephadex G-75 and carboxymethyl cellulose. By these procedures the muscle isozyme was purified about 530-fold in 29% yield, and the liver isozyme about 3600-fold in 27% yield from the respective tissue extracts. The molecular weights of the muscle and liver isozymes were estimated as about 23 500 and 30 500, respectively, by both sodium dodecyl sulfate gel electrophoresis and molecular sieve chromatography, and no subunit of either isozyme was detected. The isoelectric points of the muscle and liver isozymes were 7.0 and 8.1, respectively. The Km values of the respective enzymes for ATP and ADP were similar, but the Km(AMP) of the liver isozyme was about one-fifth of that of the muscle isozyme. Immunological studies with rabbit antiserum against the rat muscle isozyme showed that the muscle isozyme was abundant in muscle, heart and brain, while the liver isozyme was abundant in liver and kidney. PMID- 6244855 TI - Isolation of an inactive component from pig heart phosphoprotein phosphatase and its reassociation with an active component. AB - Treatment of a pig heart phosphoprotein phosphatase (phosphoprotein phosphohydrolase, EC 3.1.3.16) of Mr 224 000 with 40% ethanol followed by gel filtration on Sephadex G-150, dissociated the enzyme into an active component of Mr 31 000 and an inactive component of Mr 80 000. The inactive component reassociated with the active component, resulting in the formation of an enzyme form of Mr 123 000. A large excess of either component in the reassociation produced only this enzyme form. The ability of the inactive component to associate with the active component was lost by treatment of the inactive component with trypsin and heat (60 degrees C, 2 min) but not with DNAase and RNAase. Effects of the inactive component on the activities of the active component by the association were as followings. The inactive component: (1) stimulated slightly the 32P-H2B histone phosphatase activity in the presence of either NaCl or Mg(CH3COO)2 but inhibited strongly in the absence of the salts; (2) stimulated the 32P-H1 histone phosphatase activity in the presence of the salts; (3) inhibited the phosphorylase a phosphatase activity in the presence and absence of the salts; (4) enhanced the response to the stimulatory effects of the salts on the dephosphorylation of 32P-histone; and (5) protected the phosphorylase a phosphatase activity from inhibition by the salts. PMID- 6244856 TI - EPR study of dimerization and conformational change of Cu(II)-cytochrome c and its undeca- and octapeptide. AB - The EPR study of cytochrome c in which FE(III) ion is replaced with Cu(II) shows that there are two types of monomer (a: 4 less than pH less than 6, and b: 6 less than pH less than 11.5) and two types of dimer (A: pH less than 4 and B: pH less than 11.5) formed depending upon the pH value of the solution. Computer simulation of the EPR spectra of the dimers indicates that the structure of the dimer A has a larger lateral shift than in the dimer B. It is also shown that in monomer a, the imidazole nitrogen of 18-His is not bound to Cu(II), while it is bound in the monomer b. In the undeca- and octapeptide of Cu(II)-cytochrome c, polymers are formed in acidic solutions. As the pH is raised, depolymerization proceeds to yield the monomer and the dimer. The structure of the dimer in both peptides is found to be similar to that of the dimer B of Cu(II)-cytochrome c. In the monomer of the peptides, neither the imidazole of 18-His nor the imidazole added in excess is bound to Cu(II) in the entire pH range. It is also concluded that the dimerization in Cu(II)-porphyrins interferes with the apical coordination of basic ligand, or vice versa. PMID- 6244858 TI - Antiferromagnetic exchange interaction in the two-iron-two-sulphur ferredoxin from the blue-green alga Spirulina maxima studied with a highly sensitive magnetic balance. AB - 1. A highly sensitive magnetic balance of the Faraday type is described. 2. The magnetic susceptibility of the oxidized and reduced forms of the two-iron-two sulphur ferredoxin from the blue-green alga Spirulina maxima has been measured over a wide temperature range. 3. The results can be interpreted within a simple model involving antiferromagnetically coupled iron atoms at the active site. The coupling, expressed as --J, is estimated to be 182 +/- 20/cm and 98 +5/-10 /cm for the oxidized and reduced forms, respectively. PMID- 6244857 TI - Enzymatic trimethylation of residue-72 lysine in cytochrome c. Effect on the total structure. AB - A highly purified protein methylase III from Neurospora crassa or Saccharomyces cerevisiae specifically methylates a single lysine residue of position 72 of horse heart cytochrome c. The enzymatically methylated cytochrome c has been separated from the unmethylated counterpart species by isoelectric focusing. Simultaneously, the pI values of these two species were found to be 9.49 and 10.03, respectively. Since methyl substitution increases the basicity associated with the epsilon-amino group of lysine residues, the observed decrease in pI value is in opposition to the predicted increase. Space-filling models revealed the possibility of a hydrogen bond between the oxygen of amide of residue-70 asparagine and the epsilon-amino nitrogen of residue-72 lysine in unmethylated horse heart cytochrome C. the enzymatic methylation of residue-72 lysine tends to dissociate this hydrogen bond, thereby possibly inducing the shift of 'effective charge' of the protein molecule. This paper also deals with the pI values of cytochromes c from 13 different sources, determined by the isoelectric focusing technique. PMID- 6244859 TI - [Growth factor and cell culture : FGF and EGF]. PMID- 6244860 TI - [Mitochondrial N-acetylglucosaminyl transferase connected with viral infection]. AB - A higher level of N-acetylglucosamine incorporation by proteinic and polyprenic endogenous acceptors is observed after infection by Myxovirus. This phenomenon occurs in whole mitochondria as in outer mitochondrial membranes, where it is particularly obvious with proteinic endogenous acceptors. Under viral infection, no new N-acetylglucosaminylated polyprenol is detected. In the case of infected animals as in the case of control animals, compounds P1 (extracted by chloroform/methanol 2:1) are identified by thin layer chromatography as a N acetylglucosamyl-pyrophosphoryl-dolichol and a N, N'-diacetylchitobiosyl pyrophosphoryl-dolichol. In the case of infected animals, biosynthesis of proteinic acceptors and dolichol is not modified; therefore the increase of N acetylglucosamine incorporation is not due to a modification of the endogenous acceptors level. By the use of exogenous dolichol-monophosphate we demonstrate that the increased transfer of [14C] N-acetylglucosamine into polyprenic acceptors is the result of a higher activity of the mitochondrial N acetylglucosaminyltransferase after viral infection. PMID- 6244861 TI - Numerical investigation of kinetic neuronic equations for one-dimensional neural system. AB - In the setting of a kinetic approach to neural systems a more refined model is proposed. The subsequent kinetic equations are subjected to numerical investigation. The results show that the model retains the most evident properties of transmission of information of the natural neural systems. PMID- 6244862 TI - [Effect of administration of ouabain and cyclic AMP to different rat brain regions on the course of an epileptiform reaction]. PMID- 6244863 TI - Role of glucocorticosteroid hormones on the levels of rat liver carbamoylphosphate synthase (ammonia) and arginase activity during ontogenesis. AB - In rats, hepatic carbamoylphosphate synthase (ammonia) and arginase activities are closely related during development. Activities increase sharply during the last 4 prenatal and first 4 postnatal days and during the 3rd postnatal week. Decreases are observed between 4 and 9 days after birth, and after weaning, during adolescence. During senescence activities increase again. Before birth, treatment and prednisolone is far less effective in increasing enzyme activities than during the first 2 postnatal weeks, when it seems to precipitate normal development of the 3rd postnatal week. In the 4th postnatal week the sensitivity to prednisolone treatment increases approximately 25-fold. During the 2nd postnatal week, dexamethasone proves to be more potent, on a molar base, than triamcinolone which is more potent than prednisolone and hydrocortisone. Increases in enzyme activities which are associated with increases in blood levels of glucocorticosteroids are also associated with 2- to 3-fold decreases in DNA content, i.e. with decreases in hepatocyte multiplication rate and increases in hepatocyte cell size. These phenomena may be sequelae of quantal cell cycles leading to changes in hormone response capacity or hormone response sensitivity. PMID- 6244864 TI - EPR study of free radicals in PMMA bone cement: a feasibility study. AB - In order to determine the feasibility of using electron paramagnetic resonance (EPR) to monitor the molecular processes occurring in polymethylmethacrylate (PMMA) bone cement, a preliminary study has been conducted on the bone cement in vitro. It has been found that a sufficient concentration of free radicals is generated in the bone cement during the polymerization process so that both the polymerization and the curing can be monitored by EPR. The results of these measurements on both radiolucent and radiopaque Surgical SimplexR P bone cement are presented. It has also been found that free radicals are present in the radiopaque bone cement powder as received from the manufacturer. These radicals which apparently are produced in the radiation sterilization process have been found to be unaffected by the polymerization/curing process and to be stable for temperatures below about 100 degrees C. It has clearly been shown that EPR can used to monitor the molecular processes of bone cement in vitro. It is hoped that this technique can be utilized to monitor the in vivo ageing process of bone cement used to fix orthopedic implants. PMID- 6244865 TI - Phylogeny and ontogeny of hormone receptors: the selection theory of receptor formation and hormonal imprinting. PMID- 6244866 TI - Effect of agents that alter cyclic AMP on arachidonate-induced platelet aggregation in the dog. PMID- 6244867 TI - Localization of factor-VIII-related antigen in human vascular subendothelium. AB - Factor-VIII-related antigen has previously been shown to be synthesized by vascular endothelial cells. Using both an immunofluorescent staining technique and electron microscopy, we have demonstrated the presence of factor-VIII-related antigen in human vascular subendothelium. This finding may have implications in the mechanism of platelet adhesion to deendothelialized blood vessel surfaces. PMID- 6244868 TI - Effect of benzothiadiazine derivatives on cyclic nucleotide phosphodiesterase and on the tension of the aortic strip. AB - Diazoxide and chlorothiazide (0.1--1.5 mM) had a dose-dependent inhibitory effect on the rate of cAMP and cGMP hydrolysis determined in a 500-g supernatant of rat aorta homogenates; both compounds were weaker inhibitors of cAMP and cGMP hydrolysis than theophylline. cAMP and cGMP content of the aorta did not change in the presence of diazoxide or chlorothiazide; diazoxide, however, further increased the isoproterenol-induced rise in cAMP, while chlorothiazide did not. Both benzothiadiazines decreased the maximum tension of the aortic strip induced by serotonin, phenylephrine or potassium. Diazoxide was a stronger and chlorothiazide a weaker inhibitor of the contractile response than theophylline. Comparison of the biochemical and functional effects of diazoxide and chlorothiazide indicates that the inhibitory effect of these compounds on cyclic nucleotide phosphodiesterase does not by itself explain their vasodilating effect. PMID- 6244869 TI - Epstein-Barr virus-positive Burkitt's lymphoma in a German woman during pregnancy. AB - A fatal case of a Burkitt's lymphoma which occurred in a 34-year-old German woman during pregnancy is described. Nearly all organs showed either diffuse or nodular infiltration by tumor cells. Placenta and fetus were free of detectable tumor tissue. The patient had extremely high antibody titers (1 : 2056), both against Epstein-Barr virus capsid antigen (VCA) and the early antigen complex (EA). Within the tumor cells the Epstein-Barr virus-specific nuclear antigen EBNA and viral DNA was detected. A cell line established from a tumor biopsy displayed a translocation involving chromosomes 2 and 8. The role of Epstein-Barr virus in the development of Burkitt's lymphoma is discussed. PMID- 6244871 TI - Does a high fibre diet prevent the complications of diverticular disease? AB - The management of diverticular disease has altered radically with the widespread use of high fibre diet (HFD) over the past decade. However, whether this regimen has improved the prognosis in patients admitted with acute complications is still debatable. In this study the outcome of 100 such patients admitted to hospital with acute episodes of diverticular disease has been reviewed. Seventy-five per cent were treated conservatively with HFD and review after 5--7 years showed that over 90 per cent remained symptom-free, suggesting that HFD may afford protection by preventing further complications. PMID- 6244870 TI - [Intraoral minor salivary gland tumors. Report of 296 cases (author's transl)]. AB - 296 intraoral minor salivary gland tumors were observed among 702 salivary tumors. The study emphasizes a frequent palatine location, observed in more than 50 per cent of theses tumors. Pleiomorphic adenomas (or so called mixed tumors), are frequently encountered; but it is noteworthy that the proportion of muco epidermoid tumors or adenoid cystic carcinoma is higher among theses tumors than among major salivary glands; this fact explain a poor overall prognosis of minor salivary gland tumors. PMID- 6244872 TI - Investigating constipation. PMID- 6244873 TI - Successful treatment of experimental B virus (Herpesvirus simiae) infection with acyclovir. AB - The efficacy of the new nucleoside analogue acyclovir against B virus (Herpesvirus simiae) was investigated in rabbits and Vero cells infected with 2 136 and 0.3-1.0 TCD50 of the virus respectively. In the Vero cells 1 mg of acyclovir/1 reduced the yield of virus by 90%, which was slightly less than the effect on herpes simplex virus. Results in the rabbits varied with the interval between doses, duration of treatment, and delay before starting treatment. Acyclovir controlled an otherwise lethal infection when given not less than eight hourly for 14 days. Withdrawing treatment after 9-10 days resulted in late-onset fatal disease in some rabbits. Treatment begun within 24 hours after infection gave complete protection, and rabbits first treated up to five days after infection showed a significant reduction in mortality (p less than 0.001). The plasma half life of acyclovir is twice as long in man as in rabbits and progression of the disease is much slower. Hence acyclovir may be useful for post exposure prophylaxis against B virus infection in man and possibly also for treatment of the disease. PMID- 6244874 TI - The first year of life. Diarrhoea. PMID- 6244875 TI - Tuberculin response related to the administration of foot and mouth disease, brucellosis and rabies vaccines. PMID- 6244876 TI - Word-form dyslexia. AB - In this study we have reported our investigation of two patients with an acquired dyslexia characterized by letter-by-letter reading, whole word reading being apparently impossible. It has been shown that this phenomenon of letter-by-letter reading cannot be accounted for by visual or perceptual factors nor by impairment of visual span of apprehension. The exceptionally slow speed of reading was documented and a clear relationship between word length and reading speed established. Performance on tasks considered to maximize whole word reading which at the same time prevent the possibility of letter-by-letter reading, namely, reading script and reading with tachistoscopic presentation, was impaired. The satisfactory performance of these two patients on tasks of picture interpretation suggests that the two components of the syndrome simultanagnosia, letter-by letter reading and piecemeal perception of complex scenes, are dissociable. Three alternative explanations of letter-by-letter reading are considered and we conclude that in this type of acquired dyslexia there is damage to the system through which a visual word-form is attained. PMID- 6244877 TI - Genotype-dependent sensitivity to morphine: role of different opiate receptor populations. PMID- 6244878 TI - Naloxone acts at central opiate receptors to reverse hypotension, hypothermia and hypoventilation in spinal shock. PMID- 6244879 TI - Ontogeny of opiate mechanisms in relation to the sequential development of neurons known to be components of the guinea pig's enteric nervous system. AB - The development of opiate mechanisms in the guinea pig small intestine has been studied with reference to the development of transmitter mechanisms of neurons known to be components of the enteric nervous system. At 25 days' gestation neurons and a primitive neuropil could be found in the enteric mesenchyme. At this time, markers for two enteric neurotransmitters could be demonstrated; synthesis of [3H]acetylcholine ([3H]ACh) from [3H]choline, and specific axonal uptake of [3H]5-hydroxytryptamine ([3H]5-HT). This early gut also showed high affinity stereospecific binding of [3H]diprenorphine that was antagonized by levallorphan but not dextrophan. Thus, opiate receptors are detectable in the gut as soon as neurons can be identified. Neuronal precursors, however, are probably present prior to 25 days and putative serotonergic precursors were recognizable by their uptake of [3H]5-HT into cell bodies as early as day 20. Adrenergic innervation appeared gradually between days 32 and 48. Functional innervation of the longitudinal layer of smooth muscle was established much later in ontogeny. Spontaneous tone and a tetrodotoxin-sensitive 5-HT-induced relaxation of the muscle were detected at day 42 (neither norepinephrine nor ATP mediate this effect); contraction in response to ACh appeared at day 48; responses to electrical stimulation were elicited at days 50-56 and acute and chronic (tolerance-dependence) effects of opiates were apparent by day 56. The early appearance of opiate receptors is consistent with their being associated with either cholinergic or serotonergic neurons, or both. These early opiate receptors suggest that opiates or endogenous substances that act on opiate receptors might have effects not revealed by standard indices of opiate actions. PMID- 6244880 TI - Alterations in body temperature elicited by intrahypothalamic administration of tetrodotoxin, ouabain and A23187 ionophore in the conscious cat. AB - Ouabain, tetrodotoxin, and calcium selective ionophore (A23187) were administered bilaterally into the hypothalamus of the unrestrained, fully conscious cat, while body temperature and other indicators of thermoregulatory responses were monitored continuously. Posterior hypothalamic microinjection of 2.0 to 10.0 ng or tissue perfusion with 1.1 X 10(-7) to 1.1 X 10(-8) M ouabain elicited dose dependent increases in body temperature accompanied by pinnae vasoconstriction, shivering and postural changes consistent with heat conservation. Tetrodotoxin, microinjected in doses of 0.5 and 5.0 ng or tissue perfusions with 7.8 X 10(-9) to 7.8 X 10(-7) M in the posterior hypothalamus elicited dose dependent falls in body temperature. However, tetrodotoxin microinjected into the anterior hypothalamic region elicited only increases in temperature. The calcium selective ionophore, A23187, at least at the concentrations used in this study, did not appear to produce any consistent effects on thermoregulation. These data support the hypothesis that the ionic milieu of the posterior hypothalamic region is essential in the maintenance of body temperature. Further, they suggest that increasing the [Ca++]/[Na+] acts in a manner similar to a depression in the firing frequency of a distinct population of cells, which may in turn determine in some way the "set-point" for body temperature. There is no evidence to support the concept that increasing the [Ca++]/[Na+] causes an increased release of the synaptic contents of the region. PMID- 6244882 TI - A post-anaesthetic follow-up program. AB - Experience with an in-hospital post-anaesthetic follow-up program is reported. Visits are made by a Registered Nurse, a hospital employee working under the direction of the Head of the Department of Anesthesia. Over a three-year period 21,116 of 39,239 patients receiving anaesthetics were visited. Those not visited were mainly outpatients or patients discharged early following minor surgery. Anaesthetic related minor complications were noted in 8.15% of the patients seen in follow-up. Major complications occurred in 0.37% of patients seen. PMID- 6244881 TI - Effect of tensile mechanical stress on the synthesis of metalloproteinases by rabbit coronal sutures in vitro. AB - The application of a continuous tensile mechanical stress (30 g) to explants of coronal sutures from newborn rabbits (1-2 days) produced increases in enzyme activity of 33.7% for collagenase, 95.2% for gelatinase, and 35.9% for NMP III over a 4-day culture period. All three activities were in latent form and required activation with either 4-APMA or trypsin. The increases in enzyme activities were not accompanied by an alteration in the degradation of structural proteins. This was due to the ability of the cells to synthesize an inhibitor (mol wt 29,000 daltons) which complexed the increased quantities of enzyme. This necessitated a substantial stimulation of inhibitor production because there was still a residue of free inhibitory activity in the media of stressed cultures after 4 days. We previously showed using the same model system that coronal sutures respond to tensile mechanical stress by a two-fold increase in collagen synthesis. The present data suggest that when the priority of the cell population is the synthesis of structural proteins, the inhibitor, in addition to preventing the hydrolysis of newly synthesized peptides, also maintains matrix degradation at normal turnover levels. PMID- 6244883 TI - Treatment of parotid neoplasms. AB - Over a 25-year period 124 patients were admitted to St. Joseph's Hospital, Toronto with parotid neoplasms; 102 had benign and 22 had malignant lesions. Of 75 pleomorphic adenomas, 26 were enucleated and 11 of them (42%) recurred; no instances of recurrence followed parotidectomy. In 19 patients with Warthin's tumour there were no recurrences following any of the methods of excision. Mucoepidermoid carcinoma occurred in nine patients; eight tumours were of low grade malignancy. All were treated by parotidectomy and there were no recurrences. Four patients had malignant mixed tumour--two with long-standing parotid masses; in three patients this malignant tumour occurred years after regional radiotherapy. Facial weakness was permanent in three patients after total parotidectomy. The correct treatment of parotid neoplasms is superficial parotidectomy or, for deep lobe tumours, total parotidectomy. Radiotherapy is used for unresectable or suspected residual carcinoma. PMID- 6244884 TI - Adenoid cystic carcinoma of the salivary glands. AB - Among 334 malignant tumours of the salivary glands 62 (18.6%) were adenoid cystic carcinomas. Although this tumour grows slowly, local recurrence and metastatic spread, particularly to lung, are common. The recommended treatment is surgical excision followed by radiotherapy. Postoperative irradiation reduces the frequency of local recurrence caused by residual microscopic disease. The 5- to 10-year actuarial survival rates were 77% and 57%, respectively. Local and regional recurrence can be eradicated by aggressive treatment, either by radical operation or a combination of operation and irradiation. PMID- 6244885 TI - Effects of diet on chemically induced bowel cancer. AB - One hundred and twenty-seven rats were fed one of four diets containing graded amounts of fibre or a diet with vitamin A supplements and were given, subcutaneously, dimethyl-hydrazine or saline. Stool weight correlated directly with fibre intake and the frequency of colonic tumours decreased as fibre intake increased. An artificial fibre-free diet was also associated with a reduction in the number of colonic tumours. Major changes were noted in the profile of bacteria from one dietary group to another but no correlation with the frequency of tumours was noted. A diet which provided vitamin A supplements sufficient to retard growth and raise serum and liver concentrations of the vitamin resulted in a modest reduction in the number of tumours. PMID- 6244887 TI - Rapid diagnosis by electron microscopy of nonbacterial gastroenteritis in children. PMID- 6244886 TI - Home parenteral nutrition. PMID- 6244888 TI - An epizootic of parainfluenza virus type 1 in a group of C57B16 mice. AB - An epizootic of respiratory troubles was noticed in a group of C57B16 mice used to study their response following inoculations of different thymic extracts. The infection was characterized by a high level of mortalities. Macroscopically, the lungs of affected animals showed red consolidated areas on the lobes. Microscopically, an acute bronchopneumonia with eosinophilic intracytoplasmic inclusion bodies in the epithelial cells of the bronchi were seen. Those lesions suggest a parainfluenza virus type 1 infection. The presence of viral particles, morphologically similar to members of the Paramyxoviridae family in lung homogenates observed under electron microscopy and the elevated serum complement fixation and hemagglutination inhibition antibody titers to parainfluenza virus type 1 confirm the diagnosis. The source of the infection is unknown but four hypothesis are proposed. Healthy animals free of demonstrable antibodies specific to parainfluenza virus type 1 were obtained and the experiment was repeated. No mortalities were observed and the animals remained free of demonstrable complement fixation and hemagglutination inhibition antibodies throughout the experiment. PMID- 6244889 TI - Toxicity of Saskatoon serviceberry to cattle. AB - Saskatoon serviceberry (Amelanchier alnifolia) twigs were administered to cattle in feed rations and by intraruminal dosing to determine the toxicity of the cyanogenic shrub. When chopped twigs were fed as 75% of the diet, cattle exhibited restlessness, shivering, loss of weight, scours and shortness of breath. Low level dosing experiments indicated a rapid turnover of hydrogen cyanide in the rumen. When potential doses were increased to 5 mg hydrogen cyanide/kg (body weight) progressive stages of poisoning developed rapidly, rumen hydrogen cyanide levels were elevated for at least three hours and the increase in heart rate correlated with the rise in blood hydrogen cyanide concentration. PMID- 6244890 TI - Inhibition of adrenergic neurotransmission in ischaemic regions of the canine left ventricle. AB - To test hypothesis that adrenergic neurotransmission is impaired in acute myocardial ischaemia, we studied contractile function of normal and ischaemic myocardium after coronary artery occlusion. For each area we compared the contractile response to left sympathetic nerve stimulation (LSS) with the response to exogenous noradrenaline (NA). Contractile response was measured with intramyocardial sonomicrometers. LSS increased aortic pressure and heart rate. NA was infused to achieve an aortic pressure equivalent to LSS and simultaneous atrial pacing matched the heart rate during LSS. In normal zones both interventions produced increased shortening equivalently. In ischaemic zones systolic expansion was unchanged during LSS, while NA improved contractile function of the same zones by decreasing systolic expansion. These responses occurred during ischaemia produced by either anterior or posterior descending coronary occlusion. Changes in regional blood flow, measured by 8 microns radiolabelled microspheres, could not account for the difference between the ischaemic regional response to LSS or NA. We conclude that acute regional ischaemia impairs adrenergic nerve transmission. PMID- 6244891 TI - The recognition and treatment of early sexually transmitted disease. PMID- 6244892 TI - Intracellular neutralization of SV40 tumor antigens following microinjection of specific antibody. PMID- 6244893 TI - Radiation leukemia virus contains two distinct viral RNAs. AB - We have analyzed the RNA genome of RadLV/VL3, a highly oncogenic murine leukemia virus. This virus is produced by a permanent cell line derived from a radiation leukemia virus-induced thymic lymphoma of C57BL/Ka mice. Two distinct RNA components were found in the virions: a 70S dimer containing two 8 kb RNA subunits and a 54S dimer containing two 5.6 kb RNAs. A nononcogenic retrovirus, BL/Ka(B), endogenous in the same strain of mice, contains only 8 kb viral RNA subunits. The linkages between both RadLV/VL3 dimers have identical thermal stabilities. Both dimers can serve as primer templates for reverse transcriptase and both produce very similar "strong-stop" cDNAs 147 +/- 1 bases long. Sequences at the 5' end of the 5.6 kb subunit contain the genes for the viral proteins p15 and p12, but the gene for p30 is either absent or partially deleted. In vitro translation of the 5.6 kb RNA yields a 100,000 molecular weight protein containing antigenic determinants which react with antibody to p15 but not with antibody to p30. In addition, cells producing RadLV/VL3 virus synthesize a novel of 1.6 kb poly(A)-containing cytoplasmic RNA which shows very little if any homology with BL/Ka(B) viral sequences. PMID- 6244894 TI - Methylation of milk-borne and genetically transmitted mouse mammary tumor virus proviral DNA. AB - The 5-methylcytosine content of mouse mammary tumor virus (MMTV)-specific DNA sequences acquired by both milk-borne infection and genetic transmission was determined for both normal and neoplastic tissues of the mouse. Using the restriction endonuclease Msp I, which cleaves at the recognition sequence 5' CCGG, and its isoschizomer Hpa II, which is inhibited by methylation of the cytosine base of the CpG dinucleotide, it can be demonstrated that MMTV proviruses acquired via germ line infection are extensively methylated at both the site for Msp I-Hpa II cleavage and the site for Hha I (5'-GCGC), which is also inhibited by base modification of the cytosine. The virus-specific sequences acquired via milk-borne infection, however, are not modified at these sites in DNA from either normal infected or transformed tissues. Finally, cellular sequences are nonspecifically hypomethylated in a phenomenon unique to transformed tissue and apparently unrelated to the specific hypomethylation of exogenously acquired MMTV proviruses. PMID- 6244895 TI - Type II DNA topoisomerases: enzymes that can unknot a topologically knotted DNA molecule via a reversible double-strand break. AB - The T4 DNA topoisomerase is a recently discovered multisubunit protein that appears to have an essential role in the initiation of T4 bacteriophage DND replication. Treatment of double-stranded circular DNA with large amounts of this topoisomerase in the absence of ATP yields new DNA species which are knotted topological isomers of the double-stranded DNA circle. These knotted DNA circles, whether covalently closed or nicked, are converted to unknotted circles by treatment with trace amounts of the T4 topoisomerase in the presence of ATP. Very similar ATP-dependent enzyme activities capable of unknotting DNA are present in extracts of Drosophila eggs. Xenopus laevis eggs and mammalian tissue culture cells. The procaryotic enzyme, DNA gyrase, is also capable of unknotting DNA. We propose that these unknotting enzymes constitute a new general class of DNA topoisomerases (type II DNA topoisomerases). These enzymes must act via mechanisms that involve the concerted cleavage and rejoining of two opposite DNA strands, such that the DNA double helix is transiently broken. The passage of a second double-stranded DNA segment through this reversible double-strand break results in a variety of DNA topoisomerization reactions, including relaxation:super-coiling; knotting:unknotting and catenation:decatenation. In support of this type of mechanism, we demonstrate that the T4 DNA topoisomerase changes the linking number of a covalently closed double-stranded circular DNA molecule only by multiples of two. We discuss the possible roles of such enzymes in a variety of biological functions, along with their probable molecular mechanisms. PMID- 6244896 TI - The structure of transposable yeast mating type loci. AB - A recombinant plasmid containing a MAT alpha mating type locus of Saccharomyces cerevisiae has been isolated by its ability to complement a sterile mat alpha mutation. The plasmid hybridizes to restriction fragments containing both active mating type loci (MATa and MAT alpha) and both silent mating type loci (HMRa and HML alpha). All loci therefore have common sequences. Recombinant lambda clones of the locihave been isolated by plaque hybridization and their structures have been compared by a heteroduplex analysis. At its center, each locus contains one of two apparently nonhomologous sequences. Loci concerned with the alpha phenotype (MAT alpha and HML alpha) contain and 850 bp alpha-specific sequence, whereas loci concerned with the a phenotype (MATa and HMRa) contain a 700 bp a specific sequence. The a- or alpha-specific sequences are surrounded by DNA sequences that are common to all loci. These homologous sequences extend for 230 bp on the left and 700 bp on the right. They appear to be unrelated to each other. Surprisingly, HML alpha and HMRa differ in their extent of homology to MATa and MAT alpha outside the above regions. HMRa lacks an extensive (700 bp) DNA sequence to the right of the large right-hand homologous region, and possibly also a small (90 bp) sequence to the left of the small left-hand homologous region, both of which are present at HML alpha, MATa and MAT alpha. Hybridization studies have shown that the 700 bp sequence is present at HMLa but absent at HMR alpha alleles. It is therefore characteristic of HML, irrespective of whether it contains a- or alpha-specific sequences. The results imply that mating type interconversion is effected by transposition of DNA sequences from HML or HMR to MAT, as predicted by the controlling element model of Oshima and Takano (1971) and the Cassette model of Hicks, Strathern and Herskowitz (1977). PMID- 6244897 TI - Generalized recombination: nucleotide sequence homology between Chi recombinational hotspots. AB - Chi sites stimulate generalized recombination catalyzed by the RecA-RecBC dependent system of E. coli. This stimulation occurs over a region of several thousand base pairs surrounding the Chi site. These sites arise by mutation at four distinct loci in bacteriophage lambda. We report here the nucleotide sequence surrounding one of these loci, chi B, located between the xis and reda genes. Alteration of a single GC base pair, by deletion or by transversion to a CG base pair, creates the Chi recombinational hotspot chi + B. In a section of 30 bp, the chi + B sequence has 23 bp in common with the chi + C sequence determined previously. We presume that some part of this common sequence is the recognition sequence for a protein which acts at a rate-limiting step of generalized recombination. PMID- 6244898 TI - The inverted repeats of Tn5 are functionally different. AB - The inverted repeats of Tn5, which have identical restriction endonuclease cleavage patterns, have different functional properties. They differ with respect to RNA polymerase binding, full promotion of neomycin resistance, the polypeptides coded for by the repeats and their function in the transposition process. There is a week RNA polymerase binding site present in one repeat and not in the other which seems to be important for neomycin resistance. The two inverted repeats code for polypeptides of different molecular weights, with each repeat appearing to encode two polypeptides. The polypeptides from only one of the repeats of Tn5 appear to be absolutely required for Tn5 transposition. PMID- 6244899 TI - C3-activating proteases on human lymphoblastoid cells superinfected with Epstein Barr Virus. PMID- 6244900 TI - Sodium periodate-induced suppressor T cells of the human in vitro antibody response. PMID- 6244901 TI - [Antibacterial activity of a solution of H202, hypochlorite, and chloramine]. PMID- 6244902 TI - Polynucleotides. LIX. Synthesis and properties of a deoxyribohexanucleotide corresponding to the EcoRI recognition sequence. PMID- 6244903 TI - [Correlation between the circadian rhythms of plasma ACTH and corticosterone, and of motor activity, evolving freely after ocular enucleation in the rat]. AB - 21, 35 and 60 days after bilateral ocular enucleation a similar phase-shift vs an environmental 12 L-12 D photoperiod was observed in the circadian rhythms of plasma ACTH and corticosterone (B) and of motor activity. This phase-shift is indicative of free-running endogenous circadian rhythms whose period was estimated at 2492-24.3 h. The rhythms' amplitude (C) appeared decreased at 21 d for both hormones, and subsequently for ACTH only, whereas the rhythms' mean levels (Co) were reduced for ACTH and augmented for B. The amount of total motor activity per day decreased progressively down to 60% of controls at 60 d. Under otherwise non-fluctuating conditions the photoperiod appears, therefore as a main synchronizer to the endogenous pace-maker(s) driving those hormonal and behavioral rhythms. PMID- 6244904 TI - A phase II study of neocarzinostatin (NSC 157365) in malignant hepatoma. An Eastern Cooperative Oncology Group pilot study. AB - Thirty evaluable patients with histologically confirmed primary liver cancer (PLC) were treated with neocarzinostatin (NCS). All patients had measurable disease and an Eastern Cooperative Oncology Group (ECOG) performance status of 1, 2, or 3. NCS 2250 units/m2 was given daily for 5 days, repeated at 28-day intervals. Hemopoietic suppression was the major side effect. In 23 of 30 patients (13 with leukopenia and 19 with thrombocytopenia), this toxic effect was documented. Other toxic effects included nausea, vomiting, allergic-type reaction, and elevation of NPN. Partial response, with a median duration of 12.7 weeks (range 4--37 weeks) was observed in seven patients. In nine patients the response was classified as no change, and in 14 patients there was progressive disease. NCS has some therapeutic activity in patients with PLC. PMID- 6244905 TI - Prostaglandins and potassium relaxation in vascular smooth muscle of the rat. The role of Na-K ATPase. AB - We explored the hypothesis that postaglandin-induced vasodilation is caused by activation of the electrogenic sodium-potassium pump which results in membrane hyperpolarization and relaxation of vascular smooth muscle. Helical strips of rat tail artery relax in response to potassium after norepinephrine-induced contractions in physiological salt solution containing a low-potassium concentration. The amplitude of this potassium relaxation is used as an index of sodium-potassium ATPase activity. It was observed that PGA1, PGE2, and PGF2alpha (10(-6) g/ml) significantly enhanced the magnitut. PGE2 caused relaxation of contractions induced by either 25 mM KCl or norepinephrine (10(-9) g/ml), and these relaxations were inhibited by 10(-4) M ouabain. Indomethacin (5.3 x 10(-6) g/ml) and meclofenamate (10(-6) g/ml) reduced the magnitude of potassium-induced relaxation by more than 30% of control. PGF2alpha (10(-5) g/ml) reversed the inhibition of potassium relaxation by meclofenamate. These observations suggest that prostaglandins induce vascular smooth muscle relaxation by stimulation of the sodium pump and that endogenous prostaglandins normally potassium relaxation. PMID- 6244906 TI - Immediate and sustained hemodynamic and clinical improvement in chronic heart failure by an oral angiotensin-converting enzyme inhibitor. AB - The hemodynamic effects of an oral angiotensin-converting enzyme inhibitor, captopril, were evaluated in 10 symptomatic patients with chronic congestive heart failure. In all patients there was a significant increase in cardiac output (average 28%), stroke volume (49%), and stroke work index (26%), along with a decrease in pulmonary capillary wedge pressure (48%), indicating improved left ventricular function. Modest decreases in heart rate and arterial pressure were also observed. In seven patients maintained on captopril therapy, repeat hemodynamic studies at 2 months revealed sustained effects. These beneficial hemodynamic effects were accompanied by clinical improvement and improved exercise tolerance during maintenance therapy. These findings suggest that captopril may be a useful therapeutic adjunct for the long-term management of patients with chronic congestive heart failure. PMID- 6244907 TI - Antigens which detect IgE antibodies in workers sensitive to toluene diisocyanate. AB - Two antigens, both containing tolyl groups, were compared for ability to detect IgE antibodies in workers hypersensitive to toluene diisocyanate. One antigen, formed by reaction of p-tolyl isocyanate with human serum albumin, detected antibodies in each of ten hypersensitive workers. A second tolyl antigen, formed by reaction of p-toluoyl chloride and human serum albumin, and therefore lacking isocyanate linkages, detected antibodies in seven of the ten workers. In RAST assays, sera from toluene diisocyanate-sensitive workers demonstrated higher binding to human serum albumin-coated control discs than did sera from non sensitive workers. The significance of this binding in calculating tolyl-reactive antibody titres is discussed. PMID- 6244908 TI - Serum 5'-nucleotidase of a breast cancer patient. AB - Serum derived from the breast cancer patient included in this study was found to be a rich source of 5'-nucleotidase. In addition, it also contains nonspecific alkaline phosphatase. The properties of 5'-nucleotidase were studied by eliminating the interference of serum non-specific alkaline phosphatase by the preliminary incubation of serum in glycine-NaOH buffer containing ethylenediamine tetraacetate and magnesium. The enzyme has a pH optimum at 9.5. It is remarkably stable when held at 50 degrees C at pH 7.5, but it readily lost activity in the acid medium at pH 4.2. It hydrolyzes both the ribo- and deoxyribo-nucleoside 5' phosphates. It has the highest preference for cytidine 5'-phosphate. Adenosine 2' or 3'- phosphates are refractory to its action. PMID- 6244909 TI - Pericentric inversion, inv(9) (p22 q32), in the father of a child with a duplication-deletion of chromosome 9 and gene dosage effect for adenylate kinase 1. AB - A pericentric inversion of chromosome 9 was detected in the father of a child with partial trisomy involving the long arms and partial monosomy of the short arms of chromosome 9. A gene dosage effect was demonstrated for adenylate kinase 1 in erythrocytes. PMID- 6244910 TI - The influence of glomerular filtration rate on uremic polyneuropathy. PMID- 6244911 TI - Adenocystic carcinoma. PMID- 6244912 TI - Effect of spironolactone on aldosterone regulation in man. PMID- 6244913 TI - Herpesviruses and cancer. PMID- 6244914 TI - The biological function of the major histocompatibility complex: hypotheses. PMID- 6244915 TI - Tumors of the small intestine. PMID- 6244916 TI - Comparative in vitro activity of cefotaxime (HR 756). AB - The in vitro activity of cefotaxime (HR 756) was tested in comparison with cefuroxime, cefamondole, cefoxitin, cefazolin, ampicillin, mezlocilline, gentamicin and amicacin. MIC values were investigated on 168 freshly isolated gram-positive and gram-negative bacteria from clinical sources. Enterococci and Pseudomonas aeruginosa behaved cefotaxime-resistant. All the other species examined showed a very good sensitivity range against cefotaxime. Cefotaxime was the most active antibiotic of our study. PMID- 6244917 TI - [Nature of deletions arising in the genome of bacterial plasmids]. PMID- 6244918 TI - [Peripheral soft tissue neoplasms]. PMID- 6244919 TI - [Combined chemo- and radiotherapy in inoperable small-cell anaplastic bronchial carcinoma (author's transl)]. AB - Combined treatment with adriamycin, cyclophosphamide and vincristine (ACO) was used in 50 out-patients with histologically verified small-cell bronchial carcinoma. In 26 patients with locally and regionally limited metastases ("limited disease") radiotherapy (3000 rad focal dose) to mediastinum, hili and tumour opacity as well as prophylactic cranial irradiation (3000 rad focal dose) were performed after 3 cycles of chemotherapy. Complete clinical remission (without endoscopic control) was achieved in 32 out of 50 patients. Remissions in patients with bilateral pulmonary or extrathoracic metastases ("extensive disease", n = 24, 12 complete remissions) only led to limited asymptomatic prolongations of life (median survival time 10 months, median remission period 5 months) despite maintenance therapy. On the other hand patients with "limited disease" had considerable life prolongation (median survival 21 months, historical control value 3--4 months). Seven out of 26 patients in this group survived for 30 months after the onset of the disease, 6 out of 26 are now in their third year after starting therapy without signs of tumour recurrence. The results show that early recognition of patients with local and regional metastases has considerable prognostic value. PMID- 6244920 TI - [A new principle in long-term treatment of essential hypertension: angiotensin converting enzyme inhibition (author's transl)]. AB - The blood pressure lowering effect of the orally effective converting-enzyme inhibitor captopril (SQ 14.225) was investigated in a double-blind study in 20 patients with moderate essential hypertension. During treatment with captopril alone (150 mg t.i.c.) blood pressure dropped from an average of 167/111 to 148/99 mm Hg lying and from 164/113 to 143/99 mm Hg upright whereby 4 patients showed normalisation of their blood pressure (less than 145/95 mm Hg). There was no significant change of pulse frequency. Addition of hydrochlorothiazide led to return to normal of blood pressure in all patients. Even after 6 months of treatment tolerance had not developed. The antihypertensive effect of captopril alone paralleled the one of hydrochlorothiazide and there were no side effects. Activity of the converting enzyme in serum as well as plasma concentrations of angiotensin II and aldosterone were clearly lowered by captopril whereas plasma renin activity increased significantly. Renal sodium and water excretion and glomerular filtration rate were not influenced. PMID- 6244921 TI - What patients with diabetes want to know about their therapy. PMID- 6244922 TI - Effective treatment of vaginitis. PMID- 6244923 TI - Luteal membrane binding of prostaglandin F2 alpha and sensitivity of corpora lutea to prostaglandin F2 alpha-induced luteolysis in pseudopregnant rats. PMID- 6244924 TI - Receptor-binding activity of highly purified bovine luteinizing hormone and thyrotropin, and their subunits. AB - Highly purified preparations of bovine TSH (bTSH) and LH (bLH) and their subunits have been obtained by affinity chromatography using immobilized antibodies directed against counterpart subunits. The purified preparations were assessed for biological activity in radioligand-receptor assays for TSH and LH. After affinity purification against bLH beta, a TSH preparation whose initial potency in the LH assay had been 0.15% that of LH, failed to compete with [125I]LH in amounts up to 100 microgram. Thus, it appears that bTSH does not bind to LH receptors in the rat testis and that interaction of less purified TSH with gonadotropin receptors is attributable to LH contamination. In contrast, LH, whose initial potency in the TSH receptor assay was 0.6% that of TSH, retained a potency of 0.004% of TSH (equivalent to 3.6 mU/mg) after immunoadsorption by anti bTSH beta. The retention of TSH receptor-binding activity by affinity-purified LH indicates that the LH molecule (like hCG) has a low intrinsic thyroid-stimulating activity. Affinity-purified LH subunits have little or no demonstrable affinity for the LH receptor in vitro. Affinity-purified TSH subunits and affinity purified LH, however, exhibit very weak receptor-binding activity in the TSH radioligand receptor assay. An evaluation of the capacity of the immunoadsorbents to remove TSH from artificial mixtures suggests that the residual binding does not result entirely from contamination, and therefore, that alpha-subunits as well as LH have some intrinsic TSH-binding activity. PMID- 6244925 TI - The changing response pattern of sheep fetal adrenal cells throughout the course of gestation. PMID- 6244926 TI - Changes in thyroidal economy in rats bearing transplantable Walker 256 carcinomas. PMID- 6244927 TI - Prostaglandin stimulation of renin release: independence of beta-adrenergic receptor activity and possible mechanism of action. AB - Using a continuous superfusion system of rat kidney cortical slices, we investigated the renin-releasing effect of prostaglandin E2 (PGE2) and its possible mechanism of action. PGE2 caused significant stimulation of renin release in a dose-dependent fashion at concentrations of 3 x 10(-6) to 10(-4) M. Isoproterenol (8 x 10(-7) M) stimulated renin release significantly, and its effect was completely abolished by propranolol (2 x 10(-5) M). PGE2-stimulated renin release was not blocked by the same dose of propranolol. Dibutyryl cAMP caused a dose-dependent increase in renin release at concentrations of 10(-5) to 5 x 10(-3) M. Theophylline (4 x 10(-3) M) had no effect on renin release, but when added to subthreshold doses of PGE2 (10(-6) M), it stimulated renin release significantly. The simultaneous addition of maximal stimulating doses of PGE2 and dibutyryl cAMP had no additive or synergistic effects. These experiments show that PGE2 causes stimulation of renin release by a direct effect on the JG cell. The renin-releasing effect of PGE2 does not depend upon the beta-adrenergic receptors but may be mediated through cAMP. PMID- 6244928 TI - Stimulus-induced corticotropin-releasing factor content and adrenocorticotropin release are augmented after unilateral adrenalectomy, independently of circulating corticosteroid levels. AB - There is evidence for a neural link between the adrenal and hypothalamus that may mediate increased corticotropin-releasing factor and ACTH secretion within seconds after bilateral adrenalectomy. These studies on young male rats tested the possibility that functional evidence for adrenal afferent nerves might be revealed by the application of ACTH-releasing stimuli after the acute ACTH and corticosteroid responses to unilateral or sham adrenalectomy had subsided. Resting ACTH and corticosterone levels were not different in the two groups 1, 3, or 7-10 days after adrenal surgery. Despite similar initial conditions, the ACTH response to ether or to laparotomy with intestinal traction (but not to ip saline injections) was greater after unilateral adrenalectomy (P less than 0.01) at times when plasma corticosterone levels were not different. Hypothalamic corticotropin-releasing factor-like activity was higher in unilaterally adrenalectomized than in sham-operated rats 2 min after exposure to ether (P less than 0.05). We conclude that these results may represent a functional demonstration of decreased inhibitory neural feedback from the adrenal to the hypothalamus after unilateral adrenalectomy, and discuss the possibility that the absence of neural feedback may contribute to the well known hyperresponsiveness of bilaterally adrenalectomized rats to ACTH-releasing stimuli. PMID- 6244929 TI - Binding sites for thyrotropin-releasing hormone in sheep nucleus accumbens resemble pituitary receptors. AB - TRH binds to sites in the nucleus accumbens-septal area of sheep brain. These sites appear to represent receptors for at least some of its behavioral effects in other species and are very similar to sheep pituitary receptors. All measurements were performed on ice to prevent peptide degradation. High affinity [3H]TRH binding in brain regions was distinguished from interfering low affinity binding by use of [3-Me-His2]TRH, a more potent and specific analog, in blank tubes at a 1-microM concentration. The nucleus accumbens-septal area, particularly the nucleus accumbens itself, showed the highest binding of any of a variety of brain regions surveyed. Binding sites in both nucleus accumbens and anterior pituitary had an equilibrium dissociation constant of about 20-40 nM, a rate constant for association of about 1-3 x 10(6) M-1 min-1, and a rate constant for dissociation of about 0.07 min-1. Seventeen TRH analogs showed closely similar potencies in competing for binding in the two tissues. Six weak analogs appeared to be more potent in the nucleus accumbens than in the pituitary, but this was an artifact of their relatively greater potency in competing for low affinity binding sites which are absent in pituitary. The only major difference between the high affinity binding sites in the two tissues was in their concentration, which was about 2- to 3-fold higher in the pituitary. PMID- 6244930 TI - Luteinizing hormone receptors and testosterone synthesis in two distinct populations of Leydig cells. AB - Dispersed cells from whole testes or from isolated interstitial tissue of mature rats, yielded two distinct populations of Leydig cells when subjected to centrifugation in a 0-40% metrizamide gradient. One population (I) was found in a fractions with a density of 1.085-1.117 g/cm3, and the other population (II) was found in fractions with a density of 1.128-1.145 g/cm3. Binding of 125I-labeled hCG by each population of cells indicated a single class of binding sites with the same high binding affinity and similar concentrations of binding sites per Leydig cell. Testosterone production per fmol gonadotropin receptor site in the absence of gonadotropin stimulation was similar for cells of each population. However, when cells from each population were incubated with increasing concentrations of hCG or dibutyryl cAMP, only Leydig cells from population II exhibited a marked increase in testosterone production. The low responsiveness of Leydig cells in population I did not appear to be a result of either damage to these cells or inhibition by non-Leydig interstitial cells in population I. PMID- 6244931 TI - Release of thyrotropin receptor from thyroid plasma membranes: effect of hydrocortisone, propranolol, and adenosine 3',5'-monophosphate. AB - Soluble TSH receptors were released into the medium when bovine thyroid plasma membranes were incubated in 0.01 M Tris-HCl, pH 7.5, at 0 or 20 C. This is a conventional hypotonic medium used in binding assays. The characteristics of binding of bovine [125I]TSH to the released TSH receptor were almost the same as those of binding to TSH receptors solubilized by lithium 3,5-diiodosalicylate or to the original plasma membrane. Released TSH receptor had two binding sites with Ka values of 0.7 x 10(10) and 0.1 x 10(8) M-1. T3, T4, KI, methimazole, and propylthiouracil had no effect on spontaneous TSH receptor release or on bovine [125I]TSH binding to solubilized TSH receptor. Hydrocortisone (10(-5)--10(-3) M) and d,l-propranolol (10(-3) M) inhibited receptor release. cAMP increased the release of TSH receptor. Hydrocortisone, d,l-propranolol, and cAMP had no effect on bovine [125I]TSH binding to solubilized or released TSH receptor. d,l Propranolol and hydrocortisone may act as membrane-stabilizing agents. cAMP stimulation of release suggests that the release mechanism could depend upon a protein kinase-phosphoprotein system. Although these studies were conducted with membranes in an unphysiological medium, receptor release may occur normally and could be a source of circulating antigen related to production of antireceptor antibody in autoimmune thyroid diseases. Release of receptors during incubation in vitro may affect the results of studies of hormone-receptor interaction. PMID- 6244933 TI - Thyrotropin binding to rat thyroid membranes: reduced capacity associated with goitrogenesis. AB - To investigate a possible role of TSH in the regulation of its own receptor, a sensitive assay of [125I]TSH tropin binding to rat thyroid membranes was used. With 1 mM MgCl2 in the buffer, Scatchard analysis of displacement of TSH gave a curvilinear plot with a high affinity, low capacity (K1, 3.4 nM; Q1, 3.1 pmol/microgram) and a low affinity, high capacity binding site (K2, 0.54 microM; Q2, 1.2 X 0.1 nmol/microgram). Feeding rats propylthiouracil led to a decrease in [125I]TSH binding (expressed either per U protein or per wet wt of tissue) that was related to the duration of treatment. Evaluation by Scatchard analysis showed that this was due to a loss of binding sites, e.g. a 50-60% decrease after 1 month of propylthiouracil treatment; affinity was actually slightly increased in the goitrous tissue. This change in the number of TSH-binding sites was readily reversed in association with the suppression of TSH in vivo either by injections of T3 for 3 days or more by feeding a normal diet for 1 month. Thus, the data are compatible with TSH, that is in high concentration in the serum of rats fed propylthiouracil, exerting a downregulatory influence on its own receptors. PMID- 6244932 TI - Description and partial characterization of thyroid hormone-specific and thyroid hormone-dependent rat liver nuclear proteins. AB - A fraction of readily elutable rat liver nuclear proteins (nuclear globulins), analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, contains two proteins which reflect the thyroid status of the animal. The larger (n-band) protein is abundant in normal rat nuclei but diminished in hypothyroidism by thyroidectomy or hypophysectomy and restored with T3 treatment. It is also diminished in starvation, during which time T3 treatment of concurrent hypothyroxinemia is ineffective in tis restoration. Refeeding restores the n-band protein in starved normal rats but not in starved thyroidectomized (Tx) rats. GH does not restore this protein in either Tx or hypophysectomized (Hx) rats. The dual requirements of euthyroidism and adequate nutrition imply that the n-band protein is thyroid hormone dependent but not thyroid hormone specific. The smaller of the two nuclear globulins, the t-band protein, is prominent in Tx or Hx rats and is not altered by additional hypometabolic factors (starvation) or by nonthyroid hormone related hypermetabolic stimuli (refeeding or GH treatment of Hx rats). It is reduced in normal or T3-treated Tx or Hx rats regardless of simultaneous hypometabolic states (starvation or nonthyroid hormone-related deficiencies of hypopituitarism) or hypermetabolic states (refeeding, liver regeneration, or hyperthyroidism). The t-band protein thus appears to be inversely thyroid hormone specific in its concentration. Electrophoretic and chromatographic analysis suggest that the n-band protein is a 125,000 mol wt subunit of a 290,000 mol wt holoprotein. The t-band protein is a 70,000 mol wt peptide which exists, in part, as a monomer but largely as a subunit of a protein complex with a mol wt greater than 100,000. PMID- 6244934 TI - In vitro biosynthesis and comparative posttranslational processing of immunoreactive precursor corticotropin/beta-endorphin by human placental and pituitary cells. PMID- 6244935 TI - Elevation of uterine angiotensin II receptors during early pregnancy in the rat. PMID- 6244936 TI - Action of cholera toxin on hormone synthesis and release in GH cells: evidence that adenosine 3',5'-monophosphate does not mediate the decrease in growth hormone synthesis caused by thyrotropin-releasing hormone. AB - We have examined the effects of cholera toxin, a specific probe for processes which are caused by an increase in cAMP, on clonal strains of rat pituitary cells (GH cells) in culture. We found that 5 ng/ml cholera toxin increased the amount of intracellular cAMP after a lag period of 30-60 min. After a similar lag period, cholera toxin increased the release of PRL into the medium by 50% and caused a decrease in intracellular PRL to 60% of control values at 90 min. PRL synthesis was increased to 100% above control after 1 week of treatment, and GH synthesis was elevated to 280% above control. TRH caused an increase in PRL release and synthesis but a decrease of GH synthesis. Depending on the dose, TRH prevented or reduced the cholera toxin-induced rise in GH synthesis. We conclude that the decrease in GH synthesis caused by TRH is not likely to be mediated through an increase of intracellular cAMP. PMID- 6244937 TI - Ectopic alpha-adrenergic mediated accumulation of guanosine 3',5'-monophosphate in isolated adrenocortical carcinoma cells. AB - In the normal adrenal cell, epinephrine does not activate the rise of either cGMP or cAMP concentrations. In contrast, epinephrine activates the rise of cGMP but not cAMP concentrations in a concentration-dependent manner in isolated adrenocortical carcinoma cells. This effect was duplicated by the alpha adrenergic agonist, phenylepherine, but was unaffected by the beta-adrenergic agonist, isoproterenol. The epinephrine-activated increase in cGMP was blocked by the alpha-adrenergic antagonist, phentolamine, but was not interfered with by the beta-adrenergic antagonist, propranolol. Neither acetylcholine, a cholinergic agonist, nor exogenous calcium caused any increase in cGMP. The rise of cGMP maximally activated by ACTH was additive with that obtained with epinephrine. These results indicate that the adrenal neoplastic cell possesses ectopic alpha adrenergic receptors, and that epinephrine causes a rise of the cGMP level through these receptors. The data, furthermore, suggest that the receptors for ACTH and epinephrine are distinct. PMID- 6244938 TI - Characterization of ectopic alpha-adrenergic binding receptors of adrenocortical carcinoma cells. PMID- 6244939 TI - The effect of acute acidosis on the uptake of parathyroid hormone and the production of adenosine 3',5'-monophosphate by isolated perfused bone. PMID- 6244940 TI - [Effect of sex hormones on the content of prolactin receptor in the liver of female rats]. PMID- 6244941 TI - Gardner's syndrome with glandular cysts of the fundic mucosa. AB - The present study describes a family (mother and son) with Gardner's syndrome. Aside from the classical findings, gastric polyposis was found; histologically glandular cysts of the fundic mucosa were diagnosed. The occurrence of gastric polyps in Gardner's syndrome has recently been described with increasing frequency. These lesions have various histological aspects. A number of authors have noted several cases of Gardner's syndrome with glandular cysts of the fundic mucosa, but to our knowledge this is the first case of familial occurrence. PMID- 6244942 TI - Virus and its relationship to the "poor performance" syndrome. AB - Racehorses perform badly for many different reasons. Trainers often expect clinicians to determine the cause in individual cases and, more especially, where most of the immates of the stable are apparently affected by loss of form. Clinical examinations may reveal signs including fever, serous nasal discharge and the occasional cough. Haematology and blood biochemistry are commonly used aids to diagnosis in the field and may be helpful, but there is a need for facilities for virological investigations to be made readily available for use by clinicans as an adjunct to more commonplace laboratory techniques. This paper presents the background to a serious and widely publicised problem experienced by racing stables in the UK in recent years and, in discussing its epidemiology, lays emphasis on upper respiratory tract (URT) disease caused by viruses. It is suggested that, if the incidence of URT disease could be reduced, there would be a corresponding diminution of the "poor performance" syndrome. The inter relationship of viral diagnosis, epidemiology and research is discussed in terms of methology, interpreting results and limits of present day knowledge. PMID- 6244943 TI - Studies on the mechanism of transcription of nucleosomal complexes. AB - The mechanism of transcription by Escherichia coli RNA polymerase holoenzyme of chromatin assembled in vitro has been studied by two approaches. Using digestion with endodeoxyribonuclease EcoRI as a probe of mobility, it was found that nucleosome movement is slow compared to the time taken for RNA polymerase to transcribe through regions organised into nucleosomes. However, transcription leads to at least some displacement of nucleosomes relative to their original site on the DNA. In the second approach chromatin was reconstituted from extensively crosslinked histone octamers and simian virus 40 DNA. RNA chain elongation on this template is inhibited relative to non-crosslinked chromatin. This can be related to a decrease in the ability of the cross-linked histone octamers to dissociate from the DNA. PMID- 6244944 TI - Further characterization of the phosphate moiety of the adenovirus type 2 DNA binding protein. AB - The adenovirus type 2 DNA-binding protein is phosphorylated. Alkaline phosphatase treatment removes phosphate groups resulting in a decrease in molecular weight from 72000 to 70000. The dephosphorylated protein binds to single-stranded and double-stranded DNA as well as the phosphorylated protein does. Controlled chymotrypsin treatment cleaves the DNA-binding protein into two subspecies of Mr about 45000 and 25000. The 45000-Mr polypeptide contains most of the methionine residues but no phosphate and binds to DNA. The 25000-Mr polypeptide contains all the phosphate groups and shows no binding to DNA. Isoelectric focusing gels show heterogeneity of the DNA-binding protein and 15 subspecies with different charges can be observed after partial dephosphorylation by alkaline phosphatase. After extensive dephosphorylation two or three basic species with a molecular weight around 70000 are observed. Quantitative immunoprecipitation from cells labeled to equilibrium with inorganic 32PO4 gives a molar ratio of phosphate to protein of 4 -7 and direct chemical determination of the phosphate residues yields 4 mol Pi/mol protein. These results suggest that there exist subspecies of the protein moiety of the adenovirus DNA-binding protein. The DNA-binding protein isolated from infected cells after a short 'pulse' of [35S]methionine has a molecular weight which corresponds to that of the dephosphorylated protein. After a 'chase' period the molecular weight increases to 72000, but alkaline phosphatase treatment converts it to a species with the same molecular weight as the newly synthesized DNA-binding protein, indicating that the modification of the protein is due to phosphorylation. PMID- 6244945 TI - The activation of brain adenylate cyclase and brain cyclic-nucleotide phosphodiesterase by seven calmodulin derivatives. AB - 1. A comparison has been made of the ability of seven calmodulin derivatives to displace 125I-labeled calmodulin and to activate adenylate cyclase in a brain particulate fraction. The activation of brain-soluble cyclic-nucleotide phosphodiesterase by the same calmodulin derivatives was examined in parallel. 2. In general, the dose for half-maximal inhibition of 125I-labeled calmodulin binding and the apparent Km of adenylate cyclase activation were comparable in brain membranes. These concentrations were 20--40-times higher than the corresponding apparent Km values of activation of cyclic-nucleotide phosphodiesterase. 3. Modifying the single histidine residue or both tyrosine residues exerted no influence on the biological properties of calmodulin. The carboxymethylation of two methionine residues or the amidation of several carboxyl groups reduced the activation properties of calmodulin on adenylate cyclase and cyclic-nucleotide phosphodiesterase. Altering seven lysine or four arginine residues resulted in two proteins whose activation properties on adenylate cyclase and phosphodiesterase had been modified in a way suggesting that lysine and arginine residues play distinct roles in the interaction of native calmodulin with each enzyme. PMID- 6244946 TI - Purification and subunit structure of a high-molecular-weight phosphoprotein phosphatase (phosphatase II) from rat liver. AB - 1. Phosphatase II is a form of phosphoprotein phosphatase originally found in rat liver extract; it has a molecular weight of 160 000 by gel filtration and is highly active towards phosphorylase alpha. This phosphatase has been purified 1800-fold by using DEAE-cellulos (DE-52), aminohexyl--Sepharose-4B, protamine- Sepharose-4B and Sephadex G-200 chromatography. Throughout the purification steps, the original molecular weight and substrate specificity of phosphatase II were almost perfectly preserved. 2. The product of the final purification step migrated predominantly as a single protein band on non-denaturing gel electrophoresis. Sodium dodecyl sulfate gel electorphoresis revealed that the enzyme contains two types of subunit, alpha and beta, with molecular weights of 35 000 and 69 000, respectively. When treated with 0.2 M 2-mercaptoethanol at -20 degrees C, phosphatase II was dissociated to release the catalytically active alpha subunit. The beta subunit may be catalytically inactive but interacts with the alpha subunit so that phosphatase II becomes much less susceptible than the alpha subunit to inactivation by ATP or pyrophosphate. PMID- 6244948 TI - Behavior of beef-heart cytochrome c oxidase in reconstituted proteovesicles. A systemtic evaluation of the influence of phospholipid polar headgroup and fatty acyl side chains. AB - 1. Phospholipid-depleted cytochrome c oxidase is incorporated in vesicles, built up of phospholipids of known polar headgroup and fatty-acyl side chains. 2. Maximal reactivation is obtained only when the fatty-acyl side chains provide a fluid environment. 3. Fluid zwitterionic phospholipids are found to be more efficient reactivators than fluid anionic ones. 4. Irrespective of the polar headgroup type, two narrow ranges of activation energies for the enzymatic reaction are calculated from the Arrhenius plots: 81--92 kJ/mol in solid and 51- 61 kJ/mol in fluid conditions. 5. Cytochrome c oxidase is also incorporated in a series of vesicles, each built up of an equimolar amount of two phospholipids which differ in their polar headgroup type and/or their fatty-acyl side chain characteristics. From the localization of the enzyme activity profiles, obtained with these mixtures, tentative deductions are made about the preference of cytochrome c oxidase for different phospholipid molecules. PMID- 6244947 TI - The interaction of bovine pancreatic deoxyribonuclease I and skeletal muscle actin. AB - The rate of exchange of actin-bound nucleotide is decreased by a factor of about 20 when actin is complexed with DNAase I without affecting the binding constant of calcium for actin. Binding constants of DNAase I to monomeric and filamentous actin were determined to be 5 X 10(8) M-1 and 1.2 X 10(4) M-1 respectively. The depolymerisation of F-actin by DNAase I appears to be due to a shift in the G-F equilibrium of actin by DNAase I. Inhibition of the DNA-degrading activity of DNAase I by G-actin is of the partially competitive type. PMID- 6244949 TI - Kinetics of nuclease digestion of Physarum polycephalum nuclei at different stages of the cell cycle. AB - The kinetics of nuclease digestion of Physarum polycephalum nuclei by staphylococcal nuclease and DNase I has been studied at different stages of the cell cycle. Significant differences in the digestion behaviour of nuclei from metaphase and interphase have been detected with DNase I but not with staphylococcal nuclease. Furthermore the structure of newly replicated DNA in S phase differs from the bulk in that it is more easily degraded to acid-soluble products by either staphylococcal nuclease or by DNAase I. At least four types of chromatin structure can be distinguished by our digestion kinetics experiments. PMID- 6244950 TI - Photoaffinity labelling of arginine kinase and creatine kinase with a gamma-P substituted arylazido analogue of ATP. AB - 1. An ATP analogue with a photoactivated azide group attached to the gamma phosphate via an amide bond, ATP gamma-p-azidoanilide, appeared to have potential use as a photoaffinity label for the nucleotide-binding regions of ATP: guanidine phosphotransferases. Upon photolysis in the presence of lobster muscle arginine kinase and rabbit muscle creatine kinase, the analogue is converted to a potent inhibito of these two kinases. This photo-dependent inhibition is specific as it cannot be induced by azidoaniline, a mixture of azidoaniline and ATP or by ATP gamma-p-aminoanilide. Preirradiated under suitable conditions, the photoanalogue still shows a transitory inhibitory effect which, however, slowly vanishes with time (t0.5 = 3 h). 2. The photoinhibition is significantly decreased by the presence of ATP or ADP but is completely prevented by the addition of a mixture of nucleotide and guanidine substrates. Differential spectroscopy and affinity chromatography on Sepharose-ATP demonstrated the inability of photoinactivated arginine kinase and creatine kinase to recognize their nucleotide substrates. 3. Experiments with [14C]ATP gamma-p-azidoanilide indicated that photolysis is associated with an irreversible and stoichiometric binding of the ATP analogue to the enzymes. Autoradiographs made with the peptide maps corresponding to the tryptic digests of each 14C-labelled photomodified enzyme showed an unexpected highly specific labelling of the proteins. 4. Thiiol titrations of the kinases which have been subjected to various photolysis conditions led to the conclusion that the arylnitrene moiety of the photoanalogue is covalently attached to the single reactive cysteinyl side chain present in the active-site region of the two homologous kinases. This amino acid residue appears, therefore, to be located near the phosphate chain binding subsite occupied by the ATP analogue and probably also by the natural nucleotide substrates. PMID- 6244951 TI - Temperature behaviour of human serum albumin. AB - Structural alterations of albumin, their dependence on concentration and the role of free --SH groups at thermal denaturation, as well as the reversibility of thermally induced structural changes, were studied. Application of various physical methods provides information on a series of structural parameters in a major concentration range. Apart from changes of the helix content, heat treatment gives rise to beta structures which are amplified on cooling and which are correlated with the aggregation of albumin. With rising temperature and concentration the proportion of beta structures and aggregates increases. At degrees of denaturation of up to 20% complete renaturation is possibly in every case. The structure content is concentration-dependent even at room temperature. It may be that intermolecular interactions induce additional alpha-helix structures which are less stable, however, than the ones stabilized by intramolecular interactions. Unfolding of the pocket containing the free --SH group of cysteine-34 enables disulphide bridges to be formed leading to stable aggregates and irreversible structural alterations. Through binding of N ethymaleimide to free --SH groups, which blocks the formation of disulphide bridges, it is possible to prevent aggregation and irreversible conformational changes. At temperatures below 65--70 degrees C, oligomers are formed mainly via intermolecular beta structures. PMID- 6244952 TI - Studies on the association of NAD glycohydrolase with membranes in calf spleen. AB - The subcellular distribution of NAD glycohydrolase was studied by fractionation of calf spleen homogenates using differential and discontinuous density gradient centrifugations. The highest amount of NAD glycohydrolase activity was associated with microsomes, which in this tissue were found to contain, in addition to endoplasmic reticulum, a large proportion of vesicles derived from plasma membranes. The distribution pattern of NAD glycohydrolase was found to parallel that of plasma membrane markers. When microsomal vesicles were treated with digitonin, NAD glycohydrolase activity and plasma membranes specifically increased in density. We conclude that in calf spleen the bulk of NAD glycohydrolase is associated with plasma membranes. Microsomal NAD glycohydrolase was associated with sealed vesicles; its activity could not be increased by disruption of the sidedness of the vesicles. This result and further observations based on the known restricted permeability of biological membranes to charged substances, and on the activity of the enzyme with non-penetrating substrates and inhibitors, indicate that the NAD glycohydrolase active site is located on the exterior side of the vesicles. It is proposed that calf spleen NAD glycohydrolase is an ecto-enzyme. PMID- 6244953 TI - A comparison between heat-stable phosphatase inhibitors and activators from rabbit skeletal muscle and liver and their effects upon different preparations of phosphoprotein phosphatase. PMID- 6244954 TI - Specific regulation by steroid hormones of protein kinases in the endometrium. 1. Alteration by estrogen and progesterone in levels of protein kinases in rabbit endometrium. AB - The alteration in activities of multiple protein kinases has been studied in the endometrium of a rabbit treated with estrogen and progesterone. The administration of estrogen or progesterone to the castrated rabbit resulted in a remarkable increase of total activity in the cytosol fraction of the endometrium. The administration of estrogen caused an increase of type I adenosine-3',5' monophosphate-dependent (cAMP-dependent) protein kinase and a slight decrease of type II cAMP-dependent protein kinase. In contrast, the treatment with progesterone after priming administration of estrogen brought about an increase of type II cAMP-dependent protein kinase and a decrease of type I cAMP-dependent protein kinase. Therefore, the activity ratio of type II to type I decreased by estrogen and increased by progesterone. The simultaneous administration of cycloheximide abolished the stimulatory effect of respective hormones on the level of each protein kinase. The activity profile of protein kinases on DEAE cellulose column after ovulation caused by the administration of human chorionic gonadotropin to a non-castrated rabbit was similar to that of the rabbit treated with progesterone. The results presented demonstrate the specific regulation by the steroid hormones of de novo synthesis of protein kinases in the target organ. PMID- 6244955 TI - Specific regulation by steroid hormones of protein kinases in the endometrium. 2. Alteration in levels of protein kinases in human endometrium during the menstrual cycle. AB - The alteration in the levels of multiple protein kinases has been studied in human endometrium during the menstrual cycle. Protein kinases were examined in the cytosol fraction and separated by DEAE-cellulose column chromatography. The level of type I adenosine 3',5'-monophosphate-dependent (cAMP-dependent) protein kinase was higher than that of type II cAMP-dependent protein kinase at the proliferative phase. At the late secretory phase, type I cAMP-dependent protein kinase markedly decreased, whereas type II cAMP-dependent protein kinase remained at the same level. Therefore, type II cAMP-dependent protein kinase was exclusively predominant at this phase. cAMP-dependent and cAMP-independent protein kinases with protamine increased more at the late secretory phase than at the proliferative phase. The results presented demonstrate a specific alteration in protein kinase activities during the menstrual cycle and are compatible with those obtained in rabbit endometrium (the preceding paper). PMID- 6244956 TI - Studies on the lysine-binding sites of human plasminogen. The effect of ligand structure on the binding of lysine analogs to plasminogen. AB - A method is described for measuring relative binding constants of lysine and analogs of lysine to plasminogen and plasminogen 'kringle' fragments. Plasminogen or kringle fragments adsorbed to lysine-Sepharose are eluted with increasing concentrations of lysine or other ligands, the concentration of ligand required to elute 50% of the protein being taken as a measure of the binding constant. The method is simple and is not dependent on monitoring conformational changes. We confirm earlier reports that the best ligands for the lysine binding sites of plasminogen are omega-amino acids containing five or six carbons. We show further that both Glu-plasminogen (the native form with N-terminal glutamic acid) and Lys plasminogen (a degraded form with N-terminal lysine), as well as the heavy chain fragments, kringle 4 and kringle 1+2+3, have very similar properties with regard to binding specificity for omega-amino acids. For all species optimal binding is observed when the distance between the amino and carboxyl carbon is about 0.68 nm. The finding of ligands is decreased by the presence of polar atoms on the alpha and beta positions of the carbon chain of amino acids. Arginine binds relatively weakly at the lysine site and there does not appear to be a separate arginine binding site in plasminogen. PMID- 6244957 TI - The presence of DNA in ribosome-deficient plastids of heat-bleached rye leaves. AB - In leaves of rye seedlings (Secale cereale L.) grown at 32 degrees C the formation of plastid (70-S) ribosomes is specifically prevented. The resulting plastid-ribosome-deficient leaves can be used as a suitable system to identify chloroplast proteins which are translation products of cytosolic (80-S) ribosomes. The ribosome deficiency in plastids is accompanied by a bleaching of the leaves in light. In experiments aimed at finding the primary heat-sensitive event leading to ribosome deficiency the DNA of rye chloroplasts has been identified. Its properties are similar to those of chloroplast DNAs from other higher plants. The ribosome-deficient plastids isolated from heat-bleached rye leaves contained a DNA species which was indistinguishable from that of chloroplasts with regard to buoyant density in CsCl equilibrium gradients, reassociation properties and fragment patterns obtained upon cleavage by restriction endonucleases. Its quantity was comparable to that of chloroplast DNA of green leaves grown at a permissive temperature (22 degrees C). These results suggest that, unlike the effect in heat-bleached Euglena strains, lack of chloroplast DNA cannot be considered as the reason for the primary effect of high temperature in rye leaves but steps in the biosynthetic pathway of plastid ribosomes themselves must be affected more directly. PMID- 6244958 TI - Synthesis of new, highly radioactive tetrodotoxin derivatives and their binding properties to the sodium channel. AB - The Pfitzner-Moffatt oxidation procedure has been used to prepare five derivatives of tetrodotoxin by covalent attachment of the oxidized toxin to lysine, glycine, beta-alanine or ethylenediamine. These derivates reach specific radioactivities between 5 and 45 Ci/mmol. The equilibrium properties of binding of these tetrodotoxin derivatives to membrane-embedded or solubilized sodium channels from crustacean nerves have been analysed and compared to the binding properties of tritiated tetrodotoxin and saxitoxin to the same biological systems. All these highly radiolabelled derivatives associate to the tetrodotoxin binding component with properties similar to those of tetrodotoxin itself. The synthetic route described in this paper may be used to prepare other types of tetrodotoxin derivatives such as fluorescent derivatives for example. PMID- 6244959 TI - Parathyroid function and serum calcitonin in children receiving anticonvulsant drugs. AB - Serum calcitonin (CT) levels and other aspects of calcium metabolism were investigated in 40 epileptic children receiving long-term treatment with phenytoin and/or other anticonvulsant drugs, and in 38 age-matched controls. In the patients CT levels were significantly lower. Immunoreactive parathyroid hormone (iPTH) was significantly elevated exceeding the upper limit of controls in 11 patients. We also observed a highly significant correlation between iPTH and urinary cyclic AMP (cAMP) excretion but a lack of such a correlation with the renal handling of phosphate; this indicates to us a dissociation between cAMP production and phosphaturia. A significant correlation between iPTH levels and urinary hydroxyproline excretion points to a normal action of PTH on bone in the patients. The low CT levels are not due to hypocalcemia and may be directly attributed to the effects of anticonvulsant drugs. As the primary effect of CT is a direct inhibition of PTH induced calcium loss from bone, the drug-related low CT levels in association with secondary hyperparathyroidism possibly is an additional factor in anticonvulsant bone disease. PMID- 6244960 TI - Quantitative measurements of the urinary excretion of creatinine, uric acid, hypoxanthine and xanthine, uracil, cyclic AMP, and cyclic GMP in healthy newborn infants. AB - Serum creatinine, uric acid, and hypoxanthine and xanthine concentrations were determined in 17 mother-infant pairs at the time of delivery. Creatinine and uric acid levels were nearly similar, but hypoxanthine and xanthine were more than twice as high in the blood of the infants than in the blood of their mothers. In the same newborns the urinary excretion of creatinine, uric acid, hypoxanthine and xanthine, uracil, cAMP, and cGMP was measured on the first and fourth day of life. Creatinine, uracil, and cAMP increased, hypoxanthine and xanthine, and cGMP decreased, whereas the output of uric acid was nearly the same on both days. Correlations of the excreted substances to each other were calculated. PMID- 6244961 TI - Fetal rhabdomyomatous nephroblastoma. Pathologic histology and special clinical and biologic features. AB - Fetal rhabdomyomatous nephroblastoma is a very rare variant of Wilms' tumor. The special clinical and histologic features of this variant are presented on the basis of a case seen in a boy who was 13 months old at nephrectomy 8 months ago and has remained healthy since then. The tumor chiefly consists of fetal striated muscle; it occurs predominantly in infancy and early childhood and is often bilateral. Angiography shows a relative paucity of vessels. The volume of the tumor (determined by ultrasonography) decreases only slightly after preoperative radio- and chemotherapy because of a predominance of mesenchymal structures. The finding of nodular renal blastema in renal parenchyma with an apparently normal gross appearance is an argument in favor of classifying this type of tumor in the group of nephroblastomas and may explain the tendency of fetal rhabdomyomatous nephroblastoma to occur bilaterally. PMID- 6244962 TI - Myocardial ischaemia: an isolated, globally perfused rat heart model for metabolic and pharmacological studies. AB - A model of myocardial ischaemia is described and has been characterized in terms of functional, ultrastructural, electrophysiological and metabolic changes. The model fulfills a number of criteria considered to be of importance in any model of myocardial ischaemia namely (1) the myocardium is ischaemic as opposed to hypoxic, (2) the coronary flow is reduced but not totally abolished, (3) that flow reaching the ischaemic myocardium is fully oxygenated and contains a mixture of substrates. It is proposed that this model is of value for the investigation and assessment of pharmacological interventions during myocardial infarction. PMID- 6244963 TI - Generation of virus-specific cytotoxic T cells in vitro. II. Induction requirements with functionally inactivated virus preparations. AB - Using noninfectious Sendai virus preparations after selective enzymatic digestion of either of the two viral envelope glycoproteins, it was possible to study the effect of different virion-cell membrane interactions on virus-specific cytotoxic T lymphocyte (CTL) induction in vitro. Three different virus preparations having capacity for virus-cell fusion, for virus-cell adsorption or lacking the ability to bind to cell membranes, were all active in the generation of virus-specific primary and secondary cytotoxic T cells, when added to the culture. Investigations on the responder cell requirements during CTL induction revealed that activation by addition of virions lacking the capacity to bind to cells was sensitive to the depletion of adherent cells. When virions with fusion and binding capacity were presented on tumor stimulator cells, different requirements with respect to adherent cells were obtained in the primary and secondary CTL response to Sendai virus. The data indicate that different viral antigen-cell membrane interactions govern the activation phase and effector phase of antigen primed T cell populations, while sensitization of unprimed cells is dependent on the presence of adherent, perhaps antigen-presenting cells. PMID- 6244964 TI - Subpopulations of T lymphocytes from human blood differing in density and stage of maturation. AB - Previous investigations have shown that peripheral lymphocytes with a low specific gravity are much more active than are heavy lymphocytes in the proliferative response towards mitogens, antigens and allogeneic lymphocytes. We have now studied the biological significance of this difference in human peripheral T lymphocytes with two independent parameters generally regarded as maturation criteria. Heavy human T lymphocytes contain about one-third of the amount of cyclic AMP found in light T cells, but the increase in cyclic AMP produced by isoproterenol or prostaglandin E1 is much higher in the heavy T cells. The lactate dehydrogenase isoenzyme pattern of heavy human T lymphocytes is intermediate between that of human thymocytes and light T lymphocytes, the latter showing the most mature pattern. A high correlation was found between these two parameters, the cell density and the reactivity towards phytohemagglutinin. We conclude that human peripheral T lymphocytes are heterogeneous in maturation level: heavy, nonreactive T lymphocytes are less mature than light T lymphocytes. PMID- 6244965 TI - Tonic analgesic effects of delta 9-tetrahydrocannabinol as measured with the formalin test. AB - The analgesic effects of delta 9-tetrahydrocannabinol (THC), the psychoactive component of marihuana, were tested using the formalin test. Rats were treated with either THC (5 mg/kg or 10 mg/kg) or a placebo by gavage 4 h before the formalin test for analgesia was initiated. THC produced a highly significant analgesic effect against both phasic pain and tonic pain. THC is discussed as a model for the development of new analgesics or as a suitable analgesic if used with another potentiating drug. PMID- 6244966 TI - The ultrastructure of process formation following treatment with db-cAMP of a Chinese hamster ovary x Chinese hamster brain cell hybrid. PMID- 6244967 TI - Functional incorporation of the human erythrocyte chloride exchange system into plasma membranes of Friend erythroleukemic cells by Sendai virus-induced cell fusion. PMID- 6244968 TI - The co-induction of sister chromatid exchanges and virus synthesis in mammalian cells. PMID- 6244969 TI - A possible involvement of type II cAMP-dependent protein kinase in the initiation of DNA synthesis by rat liver cells. PMID- 6244970 TI - Mitochondrial release of Ca2+ during sustained nerve activity in the electric organ of Torpedo marmorata. AB - The calcium content of mitochondria isolated from the Torpedo electric organ was determined by atomic absorption spectroscopy. The mitochondrial fraction was found to contain 830 ng-atom Ca/mg protein. For comparison a fraction of isolated nerve endings contained 250 ng-atom Ca/mg protein. When tissue was continuously stimulated at a frequency of 5 Hz via the electromotor nerves, the Ca content of the mitochondrial fraction which is likely to contain both pre- and postsynaptic mitochondria was reduced proportionally to the decrease in transmitter content of the isolated nerve terminal fraction. After 5,000 pulses, the mitochondrial fraction had lost 80% of its Ca contents. When tissue was stimulated after previous perfusion with d-tubocurarine and blockade of electrical response the same number of pulses caused only a loss of 20--40% in the Ca content of the mitochondrial fraction. Release of transmitter was not affected by d tubocurarine. The results suggest that repetitive stimulation in the absence of postsynaptic receptor blockade causes loss of Ca from both nerve terminal mitochondria and mitochondria of the myotube-derived electrocytes. In the presence of d-tubocurarine Ca is lost from presynaptic mitochondria only. PMID- 6244971 TI - Preferential calcium staining of mitochondria in stimulated cholinergic nerve endings. AB - The fine structure of the Torpedo electric organ was investigated during different functional states using fixation media with elevated calcium concentrations. When electric tissue was stimulated (5,000 pulses, 5 Hz) and subsequently fixed in an s-collidine buffered aldehyde fixative containing 5 mM CaCl2 mitochondria in both nerve terminals and postsynaptic electroplaque cells showed electron-dense deposits. When tissue blocks were stimulated in the presence of d-tubocurarine (250 microM) which blocked electrical response deposits were restricted to presynaptic mitochondria. Electron-dense deposits were never observed in unstimulated tissue. The observations suggest that after stimulation mitochondria have an increased calcium binding capacity. In conjunction with previous biochemical findings (Schmidt and Zimmermann, 1980), we suggest that this increased binding capacity is due to a previous stimulation induced loss of calcium from activated mitochondria. PMID- 6244972 TI - Non-linearities of temporal summation in neurones in area 17 of the cat. AB - Sinusoidal temporal modulation of the contrast of sinusoidal gratings has been used to provide one description of the temporal properties of neurones in area 17 of the cat's visual cortex. Concurrently, the waveforms of the neurones' responses to 2 s flashes of identical gratings were examined. In most neurones, the response to the long flash was much more transient than would be expected from the shape of the temporal-frequency tuning curve. Temporal summation in cortical neurones is non-linear. PMID- 6244973 TI - Radioautographic identification of lactogen binding sites in rat median eminence using 125I-human growth hormone: evidence for a prolactin "short-loop" feedback site. AB - The binding characteristics of human growth hormone were exploited to identify radioautographically lactogen binding sites in the rat median eminence. Following systemic injection 125I-human growth hormone bound preferentially to the lateral palisade zone, a region of median eminence rich in dopamine and LHRH. Coinjection of 125I-human growth hormone with an excess of unlabeled human growth hormone or ovine prolactin, but not bovine grown hormone, competitively blocked 125I-human growth hormone binding to the external median eminence. These observation provide direct evidence of recognition sites for lactogenic hormones in a discrete region of the median eminence associated with hypothalamic regulation of hypophyseal prolactin and luteinizing hormone secretion. Median eminence lactogen binding sites may mediate presumed direct effect of lactogenic hormones on the reproductive functions of the hypophysiotropic hypothalamus. PMID- 6244975 TI - Hypothesis regarding the cellular mechanisms responsible for long-term synaptic potentiation in the hippocampus. PMID- 6244974 TI - Potentiation of excitatory postsynaptic potentials during and after repetitive stimulation in thin hippocampal sections. AB - Excitatory postsynaptic potentials (EPSPs) elicited by mossy fiber stimulation were recorded intracellularly from neurons in the CA3 region in thin hippocampal sections in vitro and potentiation of the EPSPs was examined during and after repetitive stimulation. Inhibitory postsynaptic potentials (IPSPs) and seizure discharges were blocked by bicuculline and high concentrations of Mg2+. When two shocks were applied at short intervals, the second EPSP was markedly potentiated. This potentiation declined exponentially with a time-constant of about 180 ms and was unaffected by changes in ambient temperature. The amount of potentiation during a pulse train was explained by summation of potentiation by individual pulses. Post tetanic potentiation lasted longer in media containing Ca2+ at higher concentrations and Mg2+ at lower concentrations. At high Ca2+ concentrations, tetanic stimulation induced long-term potentiation which was occasionally preceded by a long-lasting suppression. Tetanus to a bundle of mossy fibers potentiated EPSPs elicited by stimulation of a separate bundle of mossy fibers (heterosynaptic potentiation) but did not augment EPSPs elicited by fimbrial stimulation. PMID- 6244976 TI - Negative potentials evoked by nucleus reticularis gigantocellularis in the spinal trigeminal tract of the cat. PMID- 6244977 TI - Stimulation-produced analgesia in rats: assessment by two pain tests and correlation with self-stimulation. PMID- 6244978 TI - Fasciola hepatica: effect of 4-amino-6-trichloroethenyl-1,3-benzenedisulfonamide on glycolysis in vitro. PMID- 6244979 TI - Modulation of extracellular calcium and its functional implications. AB - Changes in [Ca2+]0 are known to affect axonal excitability and synaptic transmission. Ca2+ is also a major component of dendritic action potentials, and changes in [Ca2+]0 may therefore influence dendritic function. Use of the Ca2+ specific ion-selective microelectrode has shown that significant decreases in [Ca2+]0 occur in stimulated neuronal ensembles. Such changes are greatly enhanced during spreading depression and anoxia. The changes appear to be the result of Ca2+ entry into cells during activity, since the diffusion characteristics of Ca2+ in the extracellular space are not unusual. Decreases in [Ca2+]0 would lower the threshold for neuronal excitability but reduce synaptic transmission; rough numerical estimates of these effects are compiled. These are sufficiently large under some conditions to suggest, but not prove, possible modulatory effects of changes in [Ca2+]0. Variation in [Ca2+]0, however, is seen to be a valuable indicator of Ca2+-mediated processes in the nervous system. PMID- 6244980 TI - Physiological implications of K accumulation in heart muscle. AB - K+-selective microelectrodes in conjugation with the voltage clamp technique were used to examine the voltage and time dependence of K+ efflux and accumulation in cardiac muscle. K+ efflux per action potential is about 10 to 30 pmoles/cm2 per sec. Accumulation of K+ in the paracellular space plays an important role in regulation of action potential duration, so that the [K+]o prior to generation of an action potential determines the duration of following action potential. This regulation is brought about by the shift of inward rectifying K+ current along the voltage axis, so at higher [K+]o there is more outward current at plateau potentials. Monitoring [K+]o after a period of rapid beating provides quantitative data regarding Na-pump activity. The data suggest the Na-pump is electrogenic, making it difficult to assess the extent of K+ accumulation from the measurements of resting potential alone. These studies indicate that changes in [K+]o not only reflect outward membrane currents and Na-pump activity, but also play an important physiological regulatory role in determining the duration of the action potential. PMID- 6244981 TI - Phosphorylation by cyclic adenosine 3':5'-monophosphate-dependent protein kinase regulates myosin light chain kinase. AB - Smooth muscle myosin light chain kinase, purified to homogeneity, has a molecular weight of 130,000 +/- 5,000 in sodium dodecyl sulfate polyacrylamide gel electrophoresis. The purified enzyme has a specific activity under maximal conditions of 30 mumol Pi transferred to myosin light chain/mg kinase/min at 24 C and is totally dependent on calmodulin and calcium for activity. Incubation of myosin kinase with the catalytic subunit of cyclic adenosine 3':5'-monophosphate dependent protein kinase results in the covalent incorporation of up to one mol of phosphate per mol of myosin kinase in the absence of bound calmodulin. Limited tryptic digestion of the radioactively labeled kinase indicates that all of the label has been incorporated into a single tryptic peptide (mol wt approximately 22,000), suggesting that a single site is being phosphorylated. Phosphorylation of myosin kinase lowers the rate at which the kinase phosphorylates myosin light chain. The lower rate of light chain phosphorylation is due to a weaker binding of calmodulin to the phosphorylated kinase than to the unphosphorylated kinase. Cyclic adenosine 3':5'-monophosphate-dependent phosphorylation of the kinase actin-myosin interaction represents a possible link between hormonal binding to smooth muscle receptors and muscle relaxation. A scheme for this sequence of events is presented. PMID- 6244982 TI - Adrenergic responses of the various smooth muscle layers at the human uterotubal junction. AB - The different muscle layers at the human uterotubal junction (UTJ) were mechanically separated, and 1-mm wide muscle strips were isolated and mounted in organ chambers for isometric recording of contractile activity. It was found that the adrenergic neurotransmitter noradrenalin elicited an inhibition of the spontaneous phasic activity in the inner longitudinal and the intermediate circular layers but caused a clear-cut excitatory response in the outer, spiral shaped (uterine) layer. The excitatory response was totally blocked by treatment with phenoxybenzamine, an alpha-adrenoceptor antagonist, whereas the inhibitory effects were abolished after pretreatment with the beta-adrenoceptor antagonist propranolol. The data demonstrate a differentiated distribution of alpha- and beta-adrenoceptors in the smooth musculature at the proximal end of the tubal isthmus. It is suggested that this arrangement might serve an important purpose in the physiologic control of ovum transport in women. PMID- 6244983 TI - The effects of conjugated estrogens on gonadotropins. PMID- 6244984 TI - Inhibition of adrenal steroidogenesis by danazol in vivo. PMID- 6244985 TI - Studies of nonoxynol-9. I. The effect on the vaginas of rabbits and rats. AB - A standard rabbit vaginal irritation test was used to evaluate the morphologic reaction to an aqueous solution of a nonionic spermicidal detergent, nonoxynol-9 (N-9). Various amounts of N-9, between 2.5 mg and 50 mg, were incorporated into cylindrical collagen sponges which were retained in the vagina for 10 days. Changes in the continuity of the epithelial lining, edema of the submucosal layer, and the inflammatory cell infiltrate of this layer were proportional to the amount of N-9 tested. An increase in semiquantitative score for the inflammatory changes in the vagina was noted for increasing amounts of N-9. In young adult female rats treated vaginally with 5 mg/100 gm body weight/day of aqueous N-9 for 5 to 20 days, the number of cells (DNA) was significantly increased on day 5. The collagen content in the vaginal wall (hydroxyproline) was significantly increased after 15 and 20 daily injections of the detergent. We conclude that both morphologic and chemical changes in the vagina are compatible with the inflammatory reaction induced by the detergent tested. PMID- 6244986 TI - Amenorrhea-galactorrhea syndrome caused by a benign pituitary cyst: case report. PMID- 6244987 TI - [Properties of the excitatory postsynaptic currents in the cat motor neurons]. AB - Monosynaptic supraspinal and la excitatory postsynaptic current (e. p. s. c.) recorded with the aid of voltage clamp technique at different levels of MP, revealed characteristics as follows: peak amplitude 2--18 nA, rise time 0.3--0.5 msec, half-width 0.5--1.0 msec; extrapolated reversal potential +70-+100 mV. Slow residual current (1--4 nA) followed the e. p. s. c. E. p. s. c. and e. p. s. p. s were discussed considering the current-voltage relation and analog model. PMID- 6244988 TI - [Changes in systemic hemodynamics caused by intra-arterial and intravenous autoperfusion of small blood volumes]. AB - Changes of general peripheral resistance in response to autoperfusion both prior to and after blockade of alpha- and beta-adrenoreceptors depended on its initial level: at a relatively low initial value autoperfusion increased the vascular resistance whereas at high value decreased it. During maximal shifts of hemodynamic parameters the venous return prevailed over the cardiac output. The pressor effect was practically unrelated to the way of blood administration. PMID- 6244989 TI - [Effect of stimulator substances on the contractile activity of the isolated rat myometrium against a background of various calcium permeability blockaders]. AB - Contractile effects of oxytocin, prostaglandin F2 alpha, acetylcholine, KCl, RbCl, and BaCl2 in the presence of Mn2+ and La3+ ions and other cations were studied in the rat myometrium at 37 degrees C. The effects depended mainly on the kind of the blocking agents (oxytocin in the presence of Mn2+ significantly increased muscle tone whereas in the presence of La3+, Cd2+, Mg2+ the effect was absent). The tone increase in the presence of Ca permeability blocking agents seems to be due to the effect of the agents on the intracellular sources of Ca ions. PMID- 6244990 TI - In vivo effect of three transformation-defective mutants of subgroup C avian sarcoma viruses. AB - Three transformation-defective mutants derived from avian sarcoma viruses of subgroup C, td PR-RSV-C (Vogt), td B77 (Toyoshima) and td daPR-RSV-C (isolated in our laboratory), were injected intravenously into 12-day-old chicken embryos and intraperitoneally into newly-hatched chickens. Both Brown Leghorn chickens and F1 hybrids of two inbred chicken lines (C X I) were used. Haematological changes and formation of visible tumours were evaluated in animals kept for 8-9 months. All three td mutants produced in a significant proportion of intraembryonally injected animals haematological disorders which, in certain cases, resembled the anaemic and proliferative type of erythroblastosis. Most conspicuous symptoms of erythroblastosis were seen after td daPR-RSV-C which also gave rise to two sarcomas, containing transforming viruses. The possible character of oncogenic information retained or acquired by the TD mutants is discussed. PMID- 6244991 TI - Lymphocyte sensitization detected in lymphomatous hamadryas baboons by the macrophage electrophoretic mobility assay. AB - Peripheral blood lymphocytes from lymphomatous or control Papio hamadryas monkeys were incubated in the presence of KCl-extracted proteins prepared from allogeneic lymphomatous or normal lymph nodes and from a spontaneous baboon hepatoma. Only the lymphomatous baboon lymphocyte-lymphoma antigen interaction product(s) significantly reduced the anodic electrophoretic mobility of guinea pig macrophages. PMID- 6244992 TI - The latex particle adherence assay: inhibitory effects of protein preparations. AB - The latex particle adherence to peripheral chicken lymphocytes in the presence of different concentrations of various protein preparations was examined. Non specific inhibition of adherence was observed at and above concentrations of 500 microgram/ml, whereas protein concentrations at and below 250 microgram/ml gave no significant adherence inhibition in control chicken lymphocytes. The protein concentration of 250 microgram/ml of antigens prepared from MDV-infected chicken skin and HPRS-1 cells specifically inhibited the LPA to lymphocytes of MDV infected chickens. PMID- 6244993 TI - UV-induced DNA repair synthesis in patients with epidermodysplasia verruciformis. AB - Autoradiographic technique was utilized to measure UV-induced DNA repair synthesis in 8 patients with epidermodysplasia verruciformis: 2 infected with human papillomavirus 3 (HPV 3), 4 with HPV 4, and 2 simultaneously with HPV 3 and HPV 4. Two cell populations were compared, i.e., epidermal cells derived from light-exposed and covered skin, and peripheral lymphocytes. A control group consisted of 10 healthy subjects. DNA repair was found to be normal both in the peripheral lymphocytes and in the epidermal cells from exposed and unexposed skin. The values for covered skin were even somewhat higher but this was not statistically significant. The type of HPV infection and malignant conversion had no apparent effect on DNA repair. A certain reduction of the UV-DNA repair synthesis was demonstrated in 2 patients infected with both types of viruses. PMID- 6244994 TI - Malignant mixed mesodermal tumor of the ovary. AB - Mixed mesenchymal and epithelial tumors are highly malignant neoplasms most commonly found in the uterus. Rarely, histologically identical tumors occur in the ovary. We report a 70-yr-old woman with a malignant mixed Mullerian tumor of the ovary. The tumor contained heterologous foci of immature cartilage and striated muscle, in addition to carcinosarcomatous areas. Postoperative chemotherapy was administered, but she died within 5 mth with recurrent and metastatic tumor. A review of the literature concerning extrauterine malignant mixed Mullerian tumors is added. PMID- 6244996 TI - Foot-and-mouth disease virus production in glass sphere based monolayer systems of 0.1 to 100 L medium volume. AB - The cell and virus productivity of a 3 mm glass sphere based unit process monolayer system was determined at scales of 0.1, 1, 10 and 100 litres medium capacity. Enhanced yields were obtained up to the 10L size when compared with control Roux bottle cultures. Modifications of the operating conditions of the 100L system should bring this into line with the smaller-scale units. PMID- 6244995 TI - The production of inactivated poliovaccine on serially cultivated kidney cells from captive-bred monkeys. AB - Serially cultivated kidney cells from captive-bred monkeys appear to be very suitable as cell substrate for the production of inactivated poliovaccine. Up to about the 12th generation level no differences in cell growth and virus yield were observed. Also from a safety point of view, application of such cells is preferable to primary cells from wild-caught monkeys, as no evidence was found for the presence of monkey viruses or oncogenic properties in these cells. Application of these cells for the production of inactivated poliovaccine will reduce the number of monkeys needed for this purpose about 50 times and, therefore, could contribute considerably to solve the problem of shortage of monkeys in the world. PMID- 6244997 TI - Direct enzyme linked immunosorbent assay (ELISA) for quantification of poliomyelitis virus D-antigen. AB - The proposed micro-ELISA assay by means of the double antibody method involves three steps: adsorption of type specific antiserum on micro-wells; simultaneous incubation of antigen and Horse Radish Peroxydase (HRPO) conjugated antiserum; substrate incubation followed by photometric measurement of absorbance at 403 nm. Preliminary results seem generally in good agreement with those obtained by other tests such as gel diffusion and indirect ELISA. PMID- 6244998 TI - Enzyme-linked immunosorbent assay for detection of poliovirus antigen and antibody. AB - A sensitive method is described to detect poliovirus antigen in diluted samples of semi-processed and processed Salk vaccine material using a double antibody sandwich enzyme-linked immunosorbent assay (ELISA). The introduction of a simple conjugate-blocking step permits confirmation of antigen specificity and allows evaluation of neutralising antibody concentration in the sera employed as soon as four hours after sample addition. PMID- 6245000 TI - Preliminary results on the use of human diploid fibroblasts for inactivated polio virus vaccine production. AB - Human diploid fibroblast strains WI-38 and MRC 5 can be routinely grown in Eagles medium to densities between 2x10(5) and 1x10(5) cells/cm2. Polio virus type 1 grew to higher titers in WI-38 than MRC 5; types 2 and 3 grew equally well in both strains. After inactivation with 5 mM formaldehyde at 30 degrees C immunogenicity values were obtained which compared favourably with those obtained from monkey kidney preparations. PMID- 6244999 TI - The potential of recombination for the production of foot-and-mouth disease virus vaccine strains. AB - Biological proof of recombination in foot-and-mouth disease virus has been provided by studies on a large suite of conditional lethal mutants and a recombination map of approximately 70 mutations has been produced. However, recombination is a highly variable phenomenon and this has cast doubt on its validity and certainly on its applicability to such practical purposes as the production of good vaccine strains. Evidence is presented to demonstrate (1) that the genetic map has a good correlation with the biochemical map of polypeptide coding sequence for the genome and (2) that recombinants can be isolated bearing biochemical and biological markers from both parents. Finally, the analysis of 36 recombinants from a cross involving a cattle-attenuated and a cattle-virulent virus is described. These results have enabled us to identify the location of biological properties such as a mouse virulence and good growth in BHK cells on the genome of these two parent viruses. PMID- 6245001 TI - Foot and mouth disease virus production on microcarrier-grown cells. AB - The industrial usefulness of the production of foot and mouth disease virus with microcarrier grown cells has been tested at a large scale. The vaccines, intended for pigs, prepared with such virus give a good level of immunity against virulent challenges. They are stable and free from side effects. PMID- 6245002 TI - Concentration and purification of poliovirus by immune adsorption on immobilized antibodies. AB - Antibodies to poliovirus type 1, 2 and 3 have been coupled to Sepharose 4 B. The immune sorbentia have high binding capacities for both live and inactivated virus. Bound antigen is eluted with a high concentration of ammoniumisothiocyanate. Immediately after elution the chaotropic salt is removed by gelfiltration. The antigen recovery with inactivated virus was low; however, with live virus a good recovery was obtained. Therefore, immune adsorption seems to be applicable for concentration and purification of large amounts of live poliovirus. PMID- 6245003 TI - Presence and quantification of cell substrate DNA in inactivated poliovirus vaccine. AB - In order to follow the fate of cell substrate DNA in inactivated poliovirus vaccine (IPV), experiments simulating different steps in IPV preparation were performed. For this purpose, 3H-thymidine-labeled HeLa cell DNA released during lytic infection with Mahoney type 1 poliovirus strain was used as tracer. Low speed centrifugation (1500 xg for 15 min.) of crude virus suspension removed on the average 98.5% of the total labeled cell substrate DNA. Repeated freezing and thawing of the crude virus suspension before centrifugation did not increase the residual 1.5% radioactivity found in the supernatant. This level of contamination was not significantly influenced by filtration of the supernatant through a 0.22 micrometer pore size membrane filter. DEAE-Sepharose CL-6B chromatography of poliovirus suspensions containing large amounts of 3H-thymidine labeled HeLa cell extracts completely removed the contaminating substrate DNA. These data showed that IPV free of cell substrate DNA can easily be obtained by a usual purification procedure. PMID- 6245004 TI - Cloning of the herpes simplex virus type 1 thymidine kinase gene in E. coli K 12: a selective marker for gene transfer into animal cells. AB - The Herpes Simplex Virus type 1 (HSV 1) thymidine kinase (TK) gene, carried by a 3.6 kb Bam H1 DNA fragment, was isolated and ligated to Bam H1 cleaved bacterial plasmid pBR 322. The TK gene, cloned in E. coli, is functional when it is transferred back into Eukaryotic cells, and can thus be used as a selective marker for gene transfer. PMID- 6245005 TI - Silicates: non-specific adsorbents in purification of water from viruses. AB - Amorphous silicates having small particles with large surface area, were found to have high non-specific adsorption capacity. Escherichia coli T4 bacteriophage was used as a model in this research. Investigations have shown an adsorption capacity of up to 99% on different tested commercially available silicates. Optimal conditions for the adsorption of T4 bacteriophage on various silicates were determined. Amorphous silicates may be used in purification of water from viral contaminants. A silicate-containing model unit for filtration by adsorption of viruses is described. PMID- 6245007 TI - Factors affecting E-rosette forming ability in peripheral lymphocytes of insulin dependent diabetics. PMID- 6245008 TI - [Antibodies to cytomegalovirus in ulcerative colitis and in Crohn's disease (author's transl)]. PMID- 6245006 TI - Glucoreceptor mechanisms and the control of insulin release and biosynthesis. AB - The models proposed for the means whereby the B-cell recognises glucose and related compounds as signals for insulin release and biosynthesis are discussed. The observed correlations between rates of metabolism and insulin release and biosynthesis are consistent with the substrate-site hypothesis. For glucose itself, the enzymes catalysing the phosphorylation of the sugar provide an explanation for the major characteristics of the islet responses, but for N acetylglucosamine evidence is presented that the sugar transport system fulfils this discriminatory role. Possible mechanisms whereby sugar metabolism may be linked to changes in Ca2+-handling are considered and evidence is given supporting a role for the cytosolic NADPH/NADP+ ratio and the islet content of phosphoenolpyruvate. The nature of the targets for cyclic AMP and Ca2+ is discussed and some properties of islet cAMP-dependent protein kinase are summarised. Evidence is presented for the presence of calmodulin in islets and the possible involvement of calmodulin in stimulus-secretion coupling. On the basis of these considerations a speculative hypothesis for the mechanisms involved in the B-cell responses to glucose is outlined. PMID- 6245009 TI - [Estrogen therapy in carcinoma of the breast (author's transl)]. AB - The controvery about the increase of carcinoma of the endometrium following estrogen therapy led to an investigation of the correlation between estrogen and cancer of the breast because of the close link between carcinoma of the endometrium and carcinoma of the breast. In the statistical matched pair comparison 120 cases of carcinoma of the breast were compared with thoroughly selected controls. To each patient with carcinoma of the breast a control person with essentially the same risk factors was assigned. It was found that: 1) Estrogen therapy in general does not lead to an increased risk for carcinoma of the breast. 2) The separate evaluation of different estrogen preparations showed no increase of the risk. 3) The risk was not increased by prolonged treatment with estrogen. 4) The number of patients taking conjugated estrogens was higher in the control group than in the carcinoma group. 5) The coincidence of estrogen treatment with the other risk factors of nulligravity, hypertension and obesity did not result in an increased risk for carcinoma of the breast. PMID- 6245010 TI - Mechanisms of movement in Mimosa pudica--a pharmacological approach. PMID- 6245011 TI - Purinergic modulation of cholinergic transmission. PMID- 6245012 TI - Actions of hallucinogens on ants (Formica pratensis)--III. Social behavior under the influence of LSD and tetrahydrocannabinol. PMID- 6245014 TI - Feeding experiments in the toad Bufo bufo bufo (L.): effects of extirpation of pars distalis of the pituitary gland on feeding behavior. PMID- 6245013 TI - Stress and mortality in a small marsupial (Antechinus stuartii, Macleay). PMID- 6245015 TI - Restriction and modification enzymes and their recognition sequences. PMID- 6245016 TI - Arrangement of the single-stranded fragments in E. coli bacteriophage BF23 DNA. AB - Bacteriophage BF23st(0) DNA was denatured with alkali and fractionated by agarose gel electrophoresis. Seven single-stranded fragments (designated Fragments I- VII) were identified as the major constituents of the phage DNA. The presence of several minor fragments which represent minor populations of the phage genome was also observed. The largest fragment (Fragment I) represents the intact strand of phage DNA, whereas the other fragments form the complementary strand. Thus, BF23st(0) DNA carries single-strand interruptions in only one strand. The arrangement of the major fragments in the nicked strand was determined by use of gamma-exonuclease and agarose gel electrophoresis. From the mode of action of this nuclease, and from the kinetics of release or disappearance of the fragments, the polarity of the fragments in BF23st(0) DNA was specified. In addition, the presence of two types of major phage populations differing in their composition of the fragments was demonstrated. One type has an additional nick (yielding Fragment IV and Fragment V) in a specific fragment (Fragment II) of other type. PMID- 6245018 TI - What is the role of enzymes in aging? PMID- 6245017 TI - Physical map of the dispensable region of the genome of E. coli bacteriophage BF23. AB - Using 13 deletion mutants of bacteriophage BF23, physical as well as genetic structures of that portion of the genome which is dispensable for phage growth were investigated. The dispensable region covers at least 15% of the genome of wild type BF23, extending from about 0.2 to 0.35 map unit. Restriction endonuclease (EcoRI and HindIII) cleavage sites and the sites of single-strand interruptions in this dispensable region were localized. It was found that the dispensable region contains an interruption site, which is missing in the mutant BF23st(0) used by Okada and Shimura (1980). Wild-type phage DNA is heterogeneous in the presence or absence of specific single-strand interruptions in this or in a neighboring region of the genome. PMID- 6245019 TI - [Interaction of phospholipid membranes with silica in the presence of polymeric N oxides]. PMID- 6245020 TI - [Functional state of the external respiratory apparatus in workers in silicate and gas-silicate manufacture]. PMID- 6245021 TI - Planning for posthospital care: a follow-up study. AB - Ongoing services to patients who are about to be discharged from the hospital appear to be critically needed. Whether the need for such services should be met by hospitals or community agencies requires examination. This article reports on a study that describes the posthospital needs of patients and the extent to which these needs are met subsequent to discharge. PMID- 6245022 TI - [Outpatient breast surgery]. AB - Indication, standard operative procedure and technique of ambulant diagnostic mammary surgery is shown in detail from 15 years of experience. In respect of reducing costs intraoperative quick-frozen sections and in case of malignancy radical mastectomy immediately after biopsy during continuous general anesthesia is important. By retrospective analysis we could prove that operative results in treatment of benign breast tumors by out-patient surgery or otherwise for in patients do not differ. According to an inquiry patients preferred by 60% out patient procedure. PMID- 6245023 TI - Hypothalamic sarcoidosis and hypopituitarism. AB - 4 patients with presumed pituitary hypothalamic sarcoidosis are described. 3 had histological diagnoses compatible with sarcoidosis and in the other this diagnosis was strongly suspected from chest X-rays. 2 patients presented with diabetes insipidus. ACTH reserve was diminished in 3 out of 4 and growth hormone reserve was diminished in the 3 who were tested. All 4 patients developed secondary amenorrhea. 3 patients had hypothalamic hypothyroidism. Prolactin dynamics were intact. Tomograms of the sella turcica in all 4 and computerized tomography of the hypothalamic area in 2 patients failed to reveal any abnormality. PMID- 6245024 TI - Synthetic 1-24 ACTH-stimulated insulin release in bilaterally adrenalectomized patients. AB - The plasma insulin and blood glucose responses to synthetic 1-24 ACTH were studied in 21 patients bilaterally adrenalectomized for pituitary-dependent Cushing's syndrome and in 8 healthy adults. In the adrenalectomized patients, intravenous 1-24 ACTH administration was followed by an increase in plasma insulin concentrations after 15 and 30 min and a fall in blood glucose after 30 min. In healthy subjects no significant changes in plasma insulin and blood glucose levels were found. The presence of intact adrenals seems to be the cause of the different responses of insulin to 1-24 ACTH injection in these two groups. PMID- 6245025 TI - Effect of radioiodination on the structural integrity, receptor and antibody binding activity and circulatory behavior of human choriogonadotropin. AB - Human choriogonadotropin (hCG) was labelled with 125I using a low temperature (4 degrees C), minimal chloramine-T (10 micrograms) concentration and 20-sec oxidization. The structural integrity of labelled hCG was analyzed immediately after the labelling as well as after storage for 7 and 14 days at 4 or -15 degrees C by gel filtration on a Sepharose 6B and Sephadex G-200 column and by polyacrylamide gel electrophoresis. Gel filtrations of freshly labelled hCG revealed a single radioactive peak (Kav = 0.52 and 0.33) corresponding to the intact unlabelled hCG. Polyacrylamide gel electrophoresis also showed a high homogenity of labelled hormone. The capability of freshly labelled hCG to bind to LH(hCG) receptor was 51% and to anti-hCG gamma-globulin Sepharose 4B, 94%. Storage for 14 days at 4 degrees C caused a complete change of the molecule to a smaller conformation (Kav = 0.62 and 0.41) accompanied by a marked reduction in the binding to LH(hCG) receptor (12%). The binding to specific antibody remained high (75%). No change in the structure was found when the labelled hormone was stored for 14 days at -15 degrees C. The hormones also exhibited high binding to the LH(hCG) receptor (45%) and to specific antibody (86%). SDS-polyacrylamide gel electrophoresis indicated that over 90% of the radioiodine present in labelled hCG was associated with the alpha-subunit. No difference was found in the disappearance rate of freshly labelled and fresh unlabelled hCG from the circulation of the rat after a single intravenous injection. The rate of disappearance of the structurally changed hormone was, however, markedly increased and was found to be due to the higher uptake of the hormone by the kidneys and liver. The present observations indicate that hCG retains well its structural integrity and capability to bind to LH(hCG) receptor and specific antibody when radioiodinated with the chloramine-T method. However, there occurs a rapid structural change in labelled hormone molecules under storage at 4 degrees C leading to a smaller conformation, a marked reduction in its binding capability to LH(hCG) receptor and altered metabolic clearance in the rat. PMID- 6245026 TI - Host-tumor cellular junctions: an ultrastructural study of hepatic metastases of bronchogenic oat cell carcinoma. AB - A light and electron microscopic study of a metastatic oat cell carcinoma of the lung in the liver of an elderly male is presented. In addition to the finding of a few desmosomes between the tumor cells, desmosomes were also found between the tumor cells and adjacent hepatocytes. The latter feature does not appear to have been reported previously in man. PMID- 6245027 TI - Ultrastructural studies in a case of hepatoblastoma. PMID- 6245028 TI - Cytoplasmic crystalline structures in lymphoid cells of a human renal allograft. PMID- 6245029 TI - Intranuclear filaments in xenografts of human squamous cell carcinoma in nude mice. PMID- 6245030 TI - Genetic and biochemical studies on the suppression of and a recovery from the tumorous state in higher plants. AB - Four neoplastic diseases of plants: crown gall, which is caused by Ti plasmid DNA; Black's wound tumor disease by an RNA virus; the Kostoff genetic tumors by chromosomal imbalance; and habituation, which results from a spontaneous activation of select biosynthetic systems, have been analyzed and compared. It has been found that both the development of a capacity for autonomous growth and the nature of the heritable cellular change that underlies tumorigenesis are similar in the four instances. All develop a capacity for autonomous growth as a result of the persistent activation of select biosynthetic systems, the products of which are concerned with cell growth and division. That the persistent activation of these biosynthetic systems does not involve heritable changes of an irreversible type is indicated by the finding that a reversal of the neoplastic state occurred in three of the test systems. Since the tumor cells in these instances were found to remain totipotent the results suggest that whether the normal or tumor phenotype is expressed is determined by how the genetic information is regulated in a cell. Regulation appears to be accomplished in part through positive feedback control mechanisms. Foreign genetic information could act either in a regulatory manner to persistently activate normal biosynthetic systems or it could code for one or more essential but normally limiting substance(s) and thus replace a substance(s) that in the case of the Kostoff tumors or habituation is specified by host cell genes, or it could do both. In either case, the foreign genetic information can be regulated in much the same manner as are the host cell genes to give rise to either the normal or tumor phenotype. PMID- 6245031 TI - Liposomes as vehicles for cellular incorporation of biologically active macromolecules. AB - Lipid vesicles (liposomes) have recently been shown to be a useful vehicle for the delivery of a variety of compounds to cultured cells. Using large unilamellar vesicles composed of phosphatidylserine [LUV(PS)] we were able to encapsulate poliovirus and purified poliovirus ribonucleic acid (RNA) and show that it can be delivered efficiently to cells in an infectious form. LUV-entrapped poliovirus RNA produced infectious titers 100-fold higher than comparable RNA preparations delivered to cells by other techniques. We have made a quantitative analysis of the uptake and infectivity of the vesicle-encapsulated RNA by using various ratios of RNA copies per vesicle and by determining the percentage uptake of labelled lipid and RNA by HeLa cells. PMID- 6245033 TI - Induction of 2',3'-cyclic nucleotide 3'-phosphohydrolase and morphological alterations in C6 glioma cells by dexamethasone, (3-butoxy-4-methoxybenzyl)-2 imidazolinone and prostaglandin E1. AB - Dexamethasone, RO20-1724 and prostaglandin E1 all induced morphological alterations and increased the glial specific enzyme 2',3'-cyclic nucleotide 3' phosphohydrolase (CNP) in rat C6 glioma cells in culture. Morphological alterations consisted mainly in the development of astrocytelike changes. Increases in dexamethasone-induced CNP activity was time dependent. Dexamethasone reduced cell growth rate, depending on the concentration employed. PMID- 6245034 TI - Adrenergic mechanisms for histamine H2-receptor effects on rat myometrium. PMID- 6245035 TI - [Justification of a model of regulation of agonist-antagonist hormone pairs]. AB - An attempt is made to justify the model of the regulation of agonistic antagonistic hormonal couples (in the field of the adrenal-postpituitary interrelationships). A method of synthesis for these equations is proposed. Cancerous pathology of this regulation could be due to a disturbance in the secretion or in the catabolism of vasopressin. PMID- 6245032 TI - Gene transfer and gene mapping in mammalian cells in culture. AB - The ability to transfer mammalian genes parasexually has opened new possibilities for gene mapping and fine structure mapping and offers great potential for contributing to several aspects of mammalian biology, including gene expression and genetic engineering. The DNA transferred has ranged from whole genomes to single genes and smaller segments of DNA. The transfer of whole genomes by cell fusion forms cell hybrids, which has promoted the extensive mapping of human and mouse genes. Transfer, by cell fusion, of rearranged chromosomes has contributed significantly to determining close linkage and the assignment of genes to specific chromosomal regions. Transfer of single chromosomes has been achieved utilizing microcells fused to recipient cells. Metaphase chromosomes have been isolated and used to transfer single-to-multigenic DNA segments. DNA-mediated gene transfer, simulating bacterial transformation, has achieved transfer of single-copy genes. By utilizing DNA cleaved with restriction endonucleases, gene transfer is being empolyed as a bioassay for the purification of genes. Gene mapping and the fate of transferred genes can be examined now at the molecular level using sequence-specific probles. Recently, single genes have been cloned into eucaryotic and procaryotic vectors for transfer into mammalian cells. Moreover, recombinant libraries in which entire mammalian genomes are represented collectively are a rich new source of transferable genes. Methodology for transferring mammalian genetic information and applications for mapping mammalian genes is presented and prospects for the future discussed. PMID- 6245036 TI - Effects of a new glucocorticoid, deflazacort, on pituitary-adrenal function in man: a comparison with prednisone. AB - The influence on plasma ACTH and cortisol and on blood sugar have been evaluated in seven volunteers after single oral doses of prednisone 4 mg and 8 mg and deflazacort 5 mg and 10 mg. Drugs were administered at midnight to achieve a maximum inhibitory effect on the hypothalamic-pituitary-adrenal axis. No difference was detected in the majority of cases between the high and the low dose of each drug. In particular, the results obtained with the higher doses show a significant effect of both drugs on ACTH (at hour 4 after drug administration) and on cortisol (at hours 4, 8, 12 and 16). As for blood sugar, the hyperglycemic activity of deflazacort appears to be lower than prednisone at hours 12 and 16. On the whole, the potency of deflazacort appears similar to that of prednisone. PMID- 6245037 TI - Multinucleate cells and micronucleus formation in cultured human cells exposed to 12 MeV protons and gamma-rays. AB - Cultured human cells of the EUE line were exposed to different doses of 12 MeV protons, plated and allowed to grow for 8 days; colonies were then scored for the presences of multinucleate cells and micronuclei. The frequency of both effects is an increasing function of the dose; the evaluated exponents of the dose response equation (e = bDn) are n = 1.0 %/- 0.1 for multinucleate cells and n = 1.6 +/- 0.1 for micronuclei. By comparison with the results obtained with gamma irradiations, r.b.e. values were obtained for both effects. The correlation between the logarithm of the surviving fraction and the yield of the studied effects has been proved to be statiscally significant. PMID- 6245038 TI - Properties of an endonuclease activity in Micrococcus luteus acting on gamma irradiated DNA and on apurinic DNA. AB - A protein fraction from Micrococcus luteus with endonuclease activity against gamma-irradiated DNA was isolated and characterized. An additional activity on apurinic sites could not be separated, either by sucrose gradient sedimentation or by gel filtration through Sephadex G 100. From gel filtration, a molecular weight of about 25 000 was calculated for both endonuclease activities. The endonuclease activity against gamma-irradiated DNA was stimulated five-fold with 5 mM Mg++, whereas that against apurinic sites was less dependent on the Mg++ concentration. 100 mM KCl inhibited the gamma-ray endonuclease, but not the apurinic endonuclease activity. In gamma-irradiated RNA the protein recognized 1.65 endonuclease sensitive sites per radiation induced single-strand break, among which are 0.45 alkali labile lesions in the nucleotide strand. The affinity of the enzyme for the endonuclease sensitive site was evaluated resulting in a Km value of 73 nM. PMID- 6245039 TI - Radiation damage in solid 5-halouracils: free radicals in single crystals of 5 fluorouracil. AB - X-irradiation at 300 K of single crystals of 5-fluorouracil results in the formation of two different radical species observable by e.s.r. and ENDOR spectroscopy. One is an alpha-fluoro radical RCF(CH2)R' formed by saturation of the 5,6-double bond of the pyrimidine ring. The principal values of its alpha fluorine interaction are 170, -9 and -18 G; the isotropic part of the methylene beta-proton couplings are 46.3 and 28 G, respectively; the g-tensor has principal values of 2.0029, 2.0066, and 2.0052. The other radical species is formed by enolization of the C4-carbonyl function. The resulting spin-density distribution gives rise to three observable interactions, an alpha-proton (-5.2, -14.9, -11.2 G) at C6, an OH-proton from the C4--OH group (-1.7, -5.0, -4.1 G) and a residual alpha-fluorine interaction (0,0,11.2G). Irradiation at 77 K yields an e.s.r. pattern which is tentatively assigned to the molecular anion radical. These findings are related to the radiation chemistry of solid 5-halouracils. PMID- 6245040 TI - Contextual memory in the molecular domain. AB - Contextually rich recall of past events and actions indicates the formation of complex memory traces in which many items of information are integrated. The speed of this process and the inference that large numbers of cortical neurons are involved argue against synaptic transmission of all of the information required. The intercellular electromagnetic field giving rise to the EEG may function as an additional carrier of information essential to contextual processing. Recent experiments have led to models of the neural membrane that show very great sensitivities to the intercellular field. Changes of arrayed molecular conformations in this membrane due to cooperative effects in the intercellular field may provide a contextual memory located within the dense dendritic network of the cortex. Integrative effects within the volume structure of complex electromagnetic fields may thus provide a means of high-speed contextual processing and discrimination. PMID- 6245041 TI - Electroacupuncture elevates blood cortisol levels in naive horses; sham treatment has no effect. AB - It was hypothesized that electroacupuncture releases beta-endorphin and ACTH from the pituitary. Since ACTH induces the release of cortisol from the adrenal glands, blood cortisol level should be enhanced by electroacupuncture. The present result shows that the blood cortisol levels of horses are significantly increased after 30 min of electroacupuncture treatment while the sham treatment (control) shows an insignificant effect. PMID- 6245042 TI - Enzyme-linked immunosorbent assay for detection of antibodies to varicella zoster virus. AB - A sensitive enzyme-linked immunosorbent assay (ELISA) is described for detection of varicella zoster virus (VZV) IgG antibodies. The antigen consisted of a sonicated extract of VZV-infected human embryo cells. Goat antihuman IgG peroxidase conjugate was used to detect human IgG bound to viral antigen. The results have been compared with those obtained by the indirect peroxidase antibody to membrane antigen technique (IPAMA). Comparison of titers obtained by ELISA with those obtained by IPAMA in sera of 41 medical students, six chickenpox patients and six herpes zoster patients showed good agreement between the tests as to the presence or absence of antibody. ELISA was about 88 times more sensitive than IPAMA. The specificity and sensitivity of ELISA as compared to other serologic techniques for detection of antibody to VZV is discussed. PMID- 6245043 TI - Treatment of early stage breast cancer by limited surgery and radical irradiation. PMID- 6245044 TI - Reduced fractionation and the potential of hypoxic cell sensitizers in irradiation of malignant epithelial tumors. PMID- 6245045 TI - The radiotherapeutic management of optic nerve gliomas in children. PMID- 6245046 TI - Radiotherapy of primary brain stem tumors. PMID- 6245047 TI - Contraction of dog trachealis muscle in vivo: role of alpha-adrenergic receptors. AB - Contraction, relaxation, and longitudinal tension were recorded by isometric strain gauge arches attached to cervical tracheal muscle (CTM) in 60 spontaneously breathing dogs anesthetized with pentobarbital. Intravenous norepinephrine (NE) (3 X 10(-9), 6 X 10(-9), 1.2 X 10(-8), and 2.4 x 10(-8) mol/kg) increased spontaneous mechanical activities (SMA) and caused dose related contraction of CTM in all dogs even though there was no pretreatment with beta blockers. These activities were first potentiated by propranolol and then prevented by phentolamine. NE briefly decreased SMA and induced CTM relaxation prior to the onset of contraction in one-third of dogs. Propranolol prevented this initial relaxation. CTM responses induced by NE were 1) not significantly altered by atropine, tripelennamine, bilateral vagotomy, curarization, and complete tracheal transection below transducer sites; 2) unrelated to passive constriction of cervical trachea associated with airway elongation; and 3) independent of reflexes initiated by elevations of systemic arterial pressure. The moles per kilogram doses of acetylcholine were found to exceed those of NE when their intravenous administration caused equal CTM contractions in the same dog. These findings are consistent with the existence of alpha-adrenergic receptors in CTM. PMID- 6245048 TI - Relative latency of responses of chemoreceptor afferents from aortic and carotid bodies. AB - Discharges from aortic and carotid body chemoreceptor afferents were simultaneously recorded in 18 anesthetized cats to test the hypothesis that aortic chemoreceptors, because of their proximity to the heart, respond to changes in arterial blood gases before carotid chemoreceptors. We found that carotid chemoreceptor responses to the onset of hypoxia and hypercapnia, and to the intravenously administered excitatory drugs (cyanide, nicotine, and doxapram), preceded those of aortic chemoreceptors. Postulating that this unexpected result was due to differences in microcirculation and mass transport, we also investigated their relative speed of responses to changes in arterial blood pressure. The aortic chemoreceptors responded to decreases in arterial blood pressure before the carotid chemoreceptors, supporting the idea that the aortic body has microcirculatory impediments not generally present in the carotid body. These findings strengthened the concept that carotid bodies are more suited for monitoring blood gas changes due to respiration, whereas aortic bodies are for monitoring circulation. PMID- 6245049 TI - Public health risks of environmental contaminants: heavy metals and industrial chemicals. PMID- 6245050 TI - Mild transmissible gastroenteritis in pigs suckling vaccinated sows. AB - A strain of transmissible gastroenteritis (TGE) virus of low virulence was isolated from 14-day-old pigs suckling sows vaccinated with an attenuated TGE vaccine. Diarrhea developed in suckling pigs approximately 14 days after farrowing in 4 farrowings; however, none of these pigs died from diarrhea. Diarrhea ceased after the 4th farrowing, when vaccination of sows was discontinued. Experimentally, both the field isolate and the vaccine strain were infective and in some instances lethal for 2-day-old pigs exposed orally; however, neither strain was as virulent as the Purdue strain. PMID- 6245051 TI - Progeny testing for bovine syndactyly. AB - Syndactylous donors, superovulation, embryo transfer, and fetal removal via cesarean section were used to test four Holstein-Friesian bulls suspected of being heterozygous for syndactyly. Two bulls produced syndactylous fetuses, and thus were proved heterozygous. The other two bulls each sired eight normal fetuses and were assumed to be homozygous normal. PMID- 6245052 TI - Fine control of adenylate cyclase by the phosphoenolpyruvate:sugar phosphotransferase systems in Escherichia coli and Salmonella typhimurium. AB - Inhibition of cellular adenylate cyclase activity by sugar substrates of the phosphoenolpyruvate-dependent phosphotransferase system was reliant on the activities of the protein components of this enzyme system and on a gene designated crrA. In bacterial strains containing very low enzyme I activity, inhibition could be elicited by nanomolar concentrations of sugar. An antagonistic effect between methyl alpha-glucoside and phosphoenolpyruvate was observed in permeabilized Escherichia coli cells containing normal activities of the phosphotransferase system enzymes. In contrast, phosphoenolpyruvate could not overcome the inhibitory effect of this sugar in strains deficient for enzyme I or HPr. Although the in vivo sensitivity of adenylate cyclase to inhibition correlated with sensitivity of carbohydrate permease function to inhibition in most strains studied, a few mutant strains were isolated in which sensitivity of carbohydrate uptake to inhibition was lost and sensitivity of adenylate cyclase to regulation was retained. These results are consistent with the conclusions that adenylate cyclase and the carbohydrate permeases were regulated by a common mechanism involving phosphorylation of a cellular constituent by the phosphotransferase system, but that bacterial cells possess mechanisms for selectively uncoupling carbohydrate transport from regulation. PMID- 6245053 TI - Regulation of genes coding for enzyme constituents of the bacterial phosphotransferase system. AB - Regulation of the synthesis of the proteins of the phosphoenolpyruvate:sugar phosphotransferase system was systematically studied in wild-type and mutant strains of Salmonella typhimurium and Escherichia coli. The results suggest that enzyme I and HPr as well as the glucose-specific and the mannose-specific enzymes II are synthesized by a mechanism which depends on (i) cyclic adenosine monophosphate and its receptor protein; (ii) extracellular inducer; (iii) the sugar-specific enzyme II complex which recognizes the inducing sugar; and (iv) the general energy-coupling proteins of the phosphotransferase system, enzyme I and HPr. PMID- 6245054 TI - Regulation of ornithine decarboxylase during morphogenesis of Mucor racemosus. AB - During the yeast-to-hyphae transition of the dimorphic phycomycete Mucor racemosus, there was a 30- to 50-fold increase in the activity of ornithine decarboxylase. Increased enzyme activity preceded the emergence of germ tubes and reached a maximum before conversion was completed. Subsequently, enzyme levels rapidly declined, despite the continuation of mycelial growth. Both putrescine and spermidine blocked the enzyme activity response. Protein synthesis was required for the increase in enzyme activity during morphogenesis. A combination of actinomycin D and netropsin inhibited ribonucleic acid synthesis but failed to inhibit the increase in ornithine decarboxylase activity. There was a twofold increase in the enzyme half-life during morphogenesis with either trichodermin or verrucarin to inhibit protein synthesis. PMID- 6245055 TI - Mutation in the crp gene of Salmonella typhimurium which interferes with inducer exclusion. AB - A mutation in the crp gene of Salmonella typhimurium is described which overcame the defects of ptsHI deletion mutants for growth on a number of nonphosphotransferase system compounds. This mutation abolished inducer exclusion in a leaky ptsI mutant. The possible implications for the mechanism of inducer exclusion are discussed. PMID- 6245056 TI - Metabolite gene regulation: imidazole and imidazole derivatives which circumvent cyclic adenosine 3',5'-monophosphate in induction of the Escherichia coli L arabinose operon. AB - Imidazole, histidine, histamine, histidinol phosphate, urocanic acid, or imidazolepropionic acid were shown to induce the L-arabinose operon in the absence of cyclic adenosine 3',5'-monophosphate. Induction was quantitated by measuring the increased differential rate of synthesis of L-arabinose isomerase in Escherichia coli strains which carried a deletion of the adenyl cyclase gene. The crp gene product (cyclic adenosine 3',5'-monophosphate receptor protein) and the araC gene product (P2) were essential for induction of the L-arabinose operon by imidazole and its derivatives. These compounds were unable to circumvent the cyclic adenosine 3',5'-monophosphate in the induction of the lactose or the maltose operons. The L-arabinose regulon was catabolite repressed upon the addition of glucose to a strain carrying an adenyl cyclase deletion growing in the presence of L-arabinose with imidazole. These results demonstrated that several imidazole derivatives may be involved in metabolite gene regulation (23). PMID- 6245057 TI - Purification and properties of deoxyribonucleic acid binding factor isolated from the surface of Streptococcus sanguis cells. AB - Deoxyribonucleic acid (DNA) binding factor (BF) was found in surface fluids from competent and noncompetent cells of Streptococcus sanguis strains Challis, Wicky, and Blackburn. Fluids from noncompetent cells exhibited about 10% BF activity compared with extracts from competent cells. BF from competent Wicky cells was purified to homogeneity by electrophoresis and immunodiffusion. Purified BF preparations exhibited slight endonucleolytic activity, directed mainly against single-stranded DNA. Nucleolytic and DNA binding activities present in purified BF could be separated by polyacrylamide gel electrophoresis. Purified BF was sensitive to proteolytic enzymes and to phospholipase D, and its activity was stimulated in the presence of low Triton X-100 concentrations. The protein component of BF is a single, monomeric polypeptide with a molecular weight of 56,000 and an isoelectric point of pH 5.8. Binding of purified BF to DNA was a very rapid process at the optimum temperature, pH, and ionic strength and led to the formation of fast-sedimenting complexes. Purified BF was tested for several properties. It exhibited higher affinity to single- than to double-stranded DNA. It bound poorly to glucosylated phage T4 and single-stranded, synthetic polydeoxyribonucleotides and did not bind to RNA. It protected single-stranded DNA against nuclease S(1) action but did not protect native DNA against deoxyribonuclease I action. No evidence was found for unwinding activity, using double-stranded DNA as a substrate. PMID- 6245058 TI - Identification and mapping of a second proline permease Salmonella typhimurium. AB - In this paper we demonstrate the existence of a second proline permease, gene proP, in Salmonella typhimurium. Uptake assays demonstrate that this second proline permease has 5 to 10% the uptake rate of the putP permease, the cell's major proline permease, when assayed at 20 microM proline. Genetic mapping by Hfr and P22-mediated genetic crosses placed the second proline permease gene at 92 min on the S. typhimurium genetic map, near the genes for melibiose utilization. F'-mediated complementation tests indicated that Escherichia coli also has the proP gene. PMID- 6245060 TI - Hairy root: plasmid encodes virulence traits in Agrobacterium rhizogenes. AB - Agrobacterium rhizogenes strain 15834, which incites hairy root disease in plants, harbors three large plasmids: pAr15834a (107 x 10(6) daltons), pAr15834b (154 x 10(6) daltons), and pAr15834c (258 x 10(6) daltons). Kanamycin-resistant transconjugants were selected in a cross of kanamycin-resistant derivate of strain 15834 and an avirulent recipient. The transconjugants belonging to one class were virulent and contained all three donor plasmids. These transconjugants also acquired sensitivity to the bacteriocin agrocin 84. The loss of plasmids from virulent transconjugants during growth at 37 degrees C indicated that virulence genes reside on pAr15834b, whereas agrocin 84 sensitivity genes reside on pAr15834a. The pathology induced by the virulent transconjugants containing only pAr15834b was identical to that produced by the wild-type strain of A. rhizogenes. Restriction endonuclease fragment analysis of plasmids from the transconjugants and the donor revealed that pAr15834c is a cointegrate of pAr15834a and pAr15834b. Kanamycin-resistant transconjugants belonging to a second class were avirulent and contained an altered form of pAr15834b. Strain 15834 can utilize octopine. However, this trait was not detected in any of the transconjugants. Octopine is not synthesized by infected plant tissue. PMID- 6245059 TI - Assembly of the mitochondrial membrane system: isolation of mitochondrial transfer ribonucleic acid mutants and characterization of transfer ribonucleic acid genes of Saccharomyces cerevisiae. AB - A method is described for isolating cytoplasmic mutants of Saccharomyces cerevisiae with lesions in mitochondrial transfer ribonucleic acids (tRNA's). The mutants were selected for slow growth on glycerol and for restoration of wild type growth by cytoplasmic "petite" testers that contain regions of mitochondrial deoxyribonucleic acid (DNA) with tRNA genes. The aminoacylated mitochondrial tRNA's of several presumptive tRNA mutants were analyzed by reverse-phase chromatography on RPC-5. Two mutant strains, G76-26 and G76-35, were determined to carry mutations in the cysteine and histidine tRNA genes, respectively. The cysteine tRNA mutant was used to isolate cytoplasmic petite mutants whose retained segments of mitochondrial DNA contain the cysteine tRNA gene. The segment of one such mutant (DS504) was sequenced and shown to have the cysteine, histidine, and threonine tRNA genes. The structures of the three mitochondrial tRNA's were deduced from the DNA sequence. PMID- 6245061 TI - Purification and characterization of a kanamycin nucleotidyltransferase from plasmid pUB110-carrying cells of Bacillus subtilis. AB - The nucleotidyltransferase encoded by plasmid pUB110 was purified to greater than 95% purity with a 33% yield. The enzyme is a monomeric protein with a molecular weight of 34,000. The optimum pH for activity is 5, and the optimum MgCl2 concentration for activity is 18 mM. The enzyme, which is synthesized constitutively, is stable for several weeks at 4 degrees C. This enzyme would appear to be a good model gene product for the development of a pUB110 deoxyribonucleic acid-dependent in vitro protein-synthesizing system from Bacillus subtilis. PMID- 6245062 TI - Mapping of insertion mutations in gnd of Escherichia coli with deletions defining the ends of the gene. AB - A genetic map was prepared for gnd, the gene of Escherichia coli which encodes the metabolically regulated 6-phosphogluconate dehydrogenase. Direct selection methods were used for the isolation of mutants with deletions that define the respective ends of gnd. These selections depended on the availability of a defective lysogen in which gnd was present on a lambda h80 dgnd his prophage located at the att phi 80 region of the chromosome. Mutants with deletions entering gnd from the his-distal end were selected as Gnd- TonB- mutants. Mutants with his-proximal gnd deletions were selected as Gnd-, temperature-resistant mutants of a specially prepared stable lysogen. Gnd- mutants were also isolated after mutagenesis with bacteriophage Mu cts61, and genetic tests were used to determine which mutants carry a Mu cts61 prophage in gnd. The deletion mutations were mapped against each other and against the insertion mutations through the use of F' merodiploid strains. The insertion mutations mapped at seven distinct sites in gnd; three mapped under the deletions defining the his-proximal portion of the gene and three mapped with the his-distal deletions. PMID- 6245063 TI - Salmonella typhimurium mutants defective in acetohydroxy acid synthases I and II. AB - An analysis of transposon-induced mutants shows that Salmonella typhimurium possesses two major isozymes of acetohydroxy acid synthase, the enzymes which mediate the first common step in isoleucine and valine biosynthesis. A third (minor) acetohydroxy acid synthase is present, but its significance in isoleucine and valine synthesis may be negligible. Mutants defective in acetohydroxy acid synthase II (ilvG::Tn10) require isoleucine, alpha-ketobutyrate, or threonine for growth, a mutant defective in acetohydroxy acid synthase I (ilvB::Tn5) is a prototroph, and a double mutant (ilvG::Tn10 ilvB::Tn5) requires isoleucine plus valine for growth. PMID- 6245064 TI - Isolation and characterization of lambda specialized transducing bacteriophages carrying Klebsiella pneumoniae nif genes. AB - Seve lambda dnif specialized transducing bacteriophages were isolated from Escherichia coli strains containing plasmids carrying the his-nif region of Klebsiella pneumoniae. These phages collectively carry deoxyribonucleic acid for all of the genes in the nif regulon and adjacent deoxyribonucleic acid of K. pneumoniae. The phages were isolated by using Mu insertions in the nif region to direct the integration of lambda pMu phages in nif via formation of lambda pMu-Mu dilysogens which, upon induction, yielded lambda dnif phages. This procedure should be generally applicable for isolating lambda specialized transducing phages carrying genes from E. coli or other bacteria. PMID- 6245065 TI - Structure of the principal carotenoid pigment of Cellulomonas biazotea. AB - The yellow-pigmented Cellulomonas biazotea, ATCC 486, contains a mixture of carotenoids. The principal compound is a decapreno carotenoid (C50H72O2) tentatively characterized as 2,2'-bis(4-hydroxy-3-methyl-2-butenyl)-gamma,gamma carotene on the basis of electronic absorption, infrared, proton magnetic resonance, and mass spectrometries. The carotenoid is presumed to be identical to sarcinaxanthin from Sarcina lutea pro-synon. Micrococcus luteus and, therefore, is isomeric with decaprenoxanthin from Cellulomonas dehydrogenans. PMID- 6245066 TI - Isolation and characterization of Neurospora crassa mutants impaired in feedback control of ornithine synthesis. AB - Thirty-two independent mutants were isolated which overcame the proline requirement of pro-3 mutations in Neurospora crassa. The mutations were not revertants, appeared to be allelic, were closely linked or allelic to arg-6, and in strains unable to degrade ornithine no longer suppressed the proline requirement. The suppressor mutations did not alter the levels of biosynthetic or catabolic enzymes, yet allowed accumulation of ornithine. Suppressed strains unable to degrade arginine still produced ornithine (as detected by growth) in arginine-supplemented medium. The results suggest that the suppressor mutants were impaired in the feedback inhibition of ornithine synthesis by arginine. The activity of the appropriate biosynthetic enzyme was less sensitive to inhibition by arginine. The potential usefulness of such mutations is discussed. PMID- 6245067 TI - Bacillus subtilis deoxyribonucleic acid gyrase. AB - Bacillus subtilis 168 was shown to contain a deoxyribonucleic acid (DNA) gyrase activity which closely resembled those of the enzymes isolated from Escherichia coli and Micrococcus luteus in its enzymatic requirements, substrate specificity, and sensitivity to several antibiotics. The enzyme was purified from the wild type and nalidixic acid-resistant and novobiocin-resistant mutants of B. subtilis and was functionally characterized in vitro. The genetic loci nalA and novA but not novB were shown to code for portions of the functional gyrase. Enzyme from the antibiotic-resistant mutants was resistant to the drug in vitro. The most striking observation was the remarkable similarity between the B. subtilis enzyme and other DNA gyrases, especially with respect to the oxolinic acid-induced DNA cleavage in the presence of sodium dodecyl sulfate. All of the enzymes appeared to possess the same specificity of cutting sites regardless of the source or type of DNA used. This result implies that gyrase binding to DNA is highly specific. PMID- 6245068 TI - Properties of erythromycin-inducible transposon Tn917 in Streptococcus faecalis. AB - Streptococcus faecalis strain DS16 harbors two plasmids, a conjugative plasmid, pAD1, which encodes hemolysin and bacteriocin activities, and a nonconjugative plasmid, pAD2, encoding resistance to streptomycin, kanamycin, and erythromycin, the latter of which is inducible. The erythromycin resistance determinant is located on a 3.3-megadalton transposable element designated Tn917, which could be transposed to pAD1 as well as to two other plasmids, pAm gamma 1 and pAM alpha 1. When strain DS16 was exposed to low (inducing) concentrations of erythromycin for a few hours, the frequency of Tn917 transposition from pAD2 to pAD1 increased by an order of magnitude. This induction paralleled induction of erythromycin resistance and was prevented by exposing the cells to inhibitors of deoxyribonucleic acid, ribonucleic acid or protein synthesis. The exposure of strain DS16 to inducing concentrations of erythromycin also enhanced the frequency of erythromycin-resistant transconjugants appearing during mating. Initially, cointegrate molecules, whose molecular weights were approximately the sum of pAD1 and pAD2, accounted for these transconjugants; however, as the induction time increased, pAD1::Tn917 became increasingly prominent. PMID- 6245069 TI - Ultrastructure of a magnetotactic spirillum. AB - The ultrastructure of a magnetotactic bacterium (strain MS-1) was examined by transmission, scanning, and scanning-transmission electron microscopy. The organism resembled other spirilla in general cell morphology, although some differences were detected at the ultrastructural level. Electron-dense particles within magnetotactic cells were shown by energy-dispersive X-ray analysis to be localizations containing iron. A non-magnetotactic variant of strain MS-1 lacked these novel bacterial inclusion bodies. A chain of these particles traversed each magnetotactic cell in a specific arrangement that was consistent from cell to cell, seemingly associated with the inner surface of the cytoplasmic membrane. Each particle was surrounded by an electron-dense layer separated from the particle surface by an electron-transparent region. The term "magnetosome" is proposed for the electron-dense particles with their enveloping layer(s) as found in this and other magnetotactic bacteria. PMID- 6245070 TI - Repair of x-ray-induced deoxyribonucleic acid single-strand breaks in xth mutants of Escherichia coli. AB - An exonuclease III-deficient strain of Escherichia coli K-12, BW2001 (xthA11), was unable to perform rapid repair of X-ray-induced deoxyribonucleic acid single strand breaks and appeared to have a defect in the priming of the 3'-termini necessary for initiation of repair synthesis at the breaks. This defect cannot be explained solely by the lack of exonuclease III activity, because other xth mutants tested, including a deletion mutant, repaired radiation-induced strand breaks at close to the normal rate. PMID- 6245071 TI - Is cyclic guanosine 3',5'-monophosphate a cell cycle regulator? AB - Transient increases in the intracellular level of cyclic guanosine 3',5' monophosphate have been observed at a periodicity of one generation time in two spoT strains of Escherichia coli and in Bacillus licheniformis. PMID- 6245072 TI - Physiological function of periplasmic hexose phosphatase in Salmonella typhimurium. AB - Hydrolysis of sugar phosphates by crude and purified preparations of periplasmic hexose phosphatase from Salmonella typhimurium followed Michaelis-Menten kinetics. The enzyme bound glucose 1-phosphate with high affinity (Km = 10 microM) but bound glucose 6-phosphate with low affinity (Km = 2,000 microM). The order of substrate affinities was glucose 1-phosphate greater than mannose 1 phosphate = galactose 1-phosphate greater than fructose 1-phosphate greater than glucose 6-phosphate. These results and others suggest that the physiological function of the enzyme is the periplasmic hydrolysis of hexose 1-phosphates. PMID- 6245073 TI - Evidence for a three-iron center in a ferredoxin from Desulfovibrio gigas. Mossbauer and EPR studies. AB - The tetrameric form of a Desulfovibrio gigas ferredoxin, named Fd II, mediates electron transfer between cytochrome c3 and sulfite reductase. We have studied two stable oxidation states of this protein with Mossbauer spectroscopy and electron paramagnetic resonance. We found 3 iron atoms/monomer and a spin concentration of 0.9 spins/monomer for the oxidized protein. Taken together, the EPR and Mossbauer data demonstrate conclusively the presence of a spin-coupled structure containing 3 iron atoms and labile sulfur. The Mossbauer data show also that this metal center is structurally similar, if not identical, with the low potential center of a ferredoxin from Azotobacter vinelandii, a novel cluster described recently (Emptage, M.H., Kent, T.A., Huynh, B.H., Rawlings, J., Orme Johnson, W.H., and Munck, E. (1980) J. Biol. Chem. 255, 1793-1796). PMID- 6245074 TI - Activation of endogenous phosphorylase kinase in liver glycogen pellet by cAMP dependent protein kinase. AB - Liver glycogen phosphorylase associated with the glycogen pellet was activated by a MgATP-dependent process. This activation was reduced by 90% by ethylene glycol bis(beta-aminoethyl ether)N,N,N',N'-tetraacetic acid, not affected by the inhibitor of the cAMP-dependent protein kinase, and increased 2.5-fold by the catalytic subunit of cAMP-dependent protein kinase. Low levels of free Ca2+ (8 x 10(-8) M) completely prevented the effects of the chelator. The activation of phosphorylase by MgATP was shown not to be due to formation of AMP. DEAE cellulose chromatography of the glycogen pellet separated phosphorylase from phosphorylase kinase. The isolated phosphorylase was no longer activated by MgATP in the presence or absence of the catalytic subunit of cAMP-dependent protein kinase. The isolated phosphorylase kinase phosphorylated and activated skeletal muscle phosphorylase b and the activation was increased 2- to 3-fold by the catalytic subunit of cAMP-dependent protein kinase. Mixing the isolated phosphorylase and phosphorylase kinase together restored the effects of MgATP and the catalytic subunit of cAMP-dependent protein kinase on phosphorylase activity. These findings demonstrate that the phosphorylase kinase associated with liver glycogen has regulatory features similar to those of muscle phosphorylase kinase. PMID- 6245075 TI - Differential effects of antimycin on ubisemiquinone bound in different environments in isolated succinate . cytochrome c reductase complex. PMID- 6245076 TI - Mobility of apolar lipids of reconstituted low density lipoprotein as monitored by electron spin resonance spectroscopy. PMID- 6245077 TI - Relation of fatty acid attachment to the translation and maturation of vesicular stomatitis and Sindbis virus membrane glycoproteins. PMID- 6245078 TI - The apparent Km of ATPMg for carbamyl phosphate synthetase (ammonia) in situ. PMID- 6245079 TI - Potassium-induced changes in phosphorylation and dephosphorylation of (Na+ + K+) ATPase observed in the transient state. AB - Effects of K+ and Na+ on the transient state kinetics of (Na+ + K+)-ATPase from Electrophorus electricus were examined. Exposure of the enzyme to K+ for brief intervals prior to the addition of ATP and Na+ converts the enzyme to a form (E2 . K) which is transiently less reactive than when all three ligands are added simultaneously. Enzyme is reconverted to the rapidly reacting (E1) form if Na+ is added prior to ATP. Exposure of the ATPase to K+ without Na+ for 1 to 2 h partially restores the initial phosphate (Pi) burst but greatly depresses the amount of phosphoprotein intermediate (E-P) observed. Experiments in the presence of valinomycin suggest that much of this depression in E-P is related to the presence of sealed vesicles with K+ sites sequestered in the interior. Although the results are largely consistent with a simple model in which ATP hydrolysis occurs only through the phosphoenzyme intermediate, the partial restoration of the Pi burst following long term exposure to K+ appears to be attributable to a slow change which may allow some ATP hydrolysis to occur within formation of a phosphoenzyme intermediate. PMID- 6245080 TI - Investigations of the kinetic mechanism of bovine liver fructose 1,6 bisphosphatase. PMID- 6245081 TI - Adrenocortical carcinoma protein kinase, autophosphorylating cyclic AMP-binding protein kinase 134. Purification and characterization. PMID- 6245082 TI - The mechanism of activation of bovine skeletal muscle protein kinase by adenosine 3':5'-monophosphate. PMID- 6245083 TI - Hormone receptor-mediated stimulation of adenylyl cyclase systems. Nucleotide effects and analysis in terms of a simple two-state model for the basic receptor affected enzyme. PMID- 6245084 TI - Actinomycin D binds with highest affinity to nonribosomal DNA. AB - Based on previous evidence (T.J. Lindell (1976) Nature 263, 347-350 and T.J. Lindell, A.F. O'Malley, and B. Puglisi (1978) Biochemistry 17, 1154-1160) it was anticipated that actinomycin D in a low concentration would bind to DNA which is involved in the regulation of rRNA transcription in eukaryotes. This was examined by digestion of rat (liver) DNA with EcoRI, adding [3H]actinomycin D (0.004 microgram/ml) and resolution of the restriction fragments by RPC-5 chromatography. Labeled actinomycin D was found to bind with highest affinity to a single fraction consistently eluting at 0.63 M KCl. A similar digestion and fractionation of nucleolar DNA, which is enriched in rDNA sequences, did not reveal a similar high affinity binding of actinomycin D. This fraction of DNA which binds actinomycin D with highest affinity did not contain any rDNA as evidenced by hybridization with [32P]rRNA. Therefore, at the concentration of 0.004 microgram/ml, actinomycin D does not selectively bind to rDNA as evidenced by two independent criteria. Whether this high affinity actinomycin D-binding DNA has any function in the regulation of rRNA transcription remains to be determined. PMID- 6245085 TI - Nereis cuticle collagen. Proteolysis by marine vibrial and clostridial collagenases. AB - Proteolysis of Nereis cuticle collagen by two bacterial collagenases was investigated using viscosimetry, enzyme kinetics, sodium dodecyl sulfate polyacrylamide gel electrophoresis, and ion exchange chromatography of collagenolytic peptides. Collagenase of the marine Vibrio B-30 completely degrades native cuticle collagen at 7 degress C with a turnover number 50 times greater than that of the clostridial collagenase. Although turnover numbers for the two enzymes are comparable when using denatured cuticle collagen as substrate, the vibrial collagenase appears to cleave twice as many peptide bonds per mg of cuticle collagen as does the clostridial enzyme. Sodium dodecyl sulfate gel electrophoresis of collagenase-digested native cuticle collagen reflects the resistance of the collagen to clostridial collagenase; however, the vibrial enzyme completely degrades the cuticle collagen with the formation of one transient intermediate (Mr 400,000). Peptide analysis of fully digested denatured cuticle collagen reveals that the two enzymes have a number of qualitative and quantitative similarities. Despite these, however, only the vibrial collagenase seems capable of extensively degrading native cuticle collagen. PMID- 6245086 TI - Preparation and properties of highly enriched cardiac sarcolemma from isolated adult myocytes. AB - Isolated myocytes were prepared from adult canine hearts using a combined technique of myocardial perfusion followed by incubation with collagenase. More than 60% of the cells routinely excluded trypan blue dye. Disruption of the myocytes was accomplished using high pressure nitrogen cavitation. After differential and sucrose gradient centrifugation, the peak sarcolemmal fraction averaged 100-fold enrichment in ouabain-inhibited K+-stimulated p-nitrophenyl phosphatase and 82-fold in ouabain-inhibited (Na+,K+)-ATPase. These sarcolemmal membranes are enriched in phospholipid phosphorus (1.98 mumol/mg of protein) and more than 4-fold in sphingomyelin and cholesterol. Polyacrylamide gels revealed three major protein peaks at 50,000, 91,000, and 140,000 apparent molecular weights. This work demonstrates the feasibility of preparing highly pure cardiac sarcolemma from isolated adult myocytes. The problem of cellular cross contamination due to heterogeneity of cell types in whole myocardial tissue has been circumvented. The level of enrichment exceeds all reported preparations of cardiac sarcolemma from whole myocardium and cultured myocytes. This preparation should prove to be useful as an in vitro model for studies of physiological, pharmacological, and pathological perturbations of sarcolemmal structure and function. PMID- 6245087 TI - Characterization of the binding of 125I-relaxin to rat uterus. PMID- 6245088 TI - Sarcoma growth factor from mouse sarcoma virus-transformed cells. Purification by binding and elution from epidermal growth factor receptor-rich cells. PMID- 6245089 TI - The effect of divalent cations on the mode of action of DNase I. The initial reaction products produced from covalently closed circular DNA. AB - The effect of different divalent metal ions on the hydrolysis of DNA by DNase I was studied with an assay which distinguishes between cleavage of one or both strands of the DNA substrate during initial encounters between enzyme and DNA. Using covalently closed superhelical SV40(I) DNA as substrate, initial reaction products consisting of relaxed circles or unit-length linears are resolved by electrophoresis of radioactively labeled DNA in agarose gels. Only in the presence of a transition metal ion, such as Mn2+ or Co2+, and only under certain reaction conditions, is DNase I able to cut both DNA strands at or near the same point, generating unit-length linears. This ability to cut both DNA strands is inhibited by such factors as temperature decrease, the addition of a monovalent ion or another divalent cation which is not a transition metal ion, or a reduction in the number of superhelical turns in the DNA substrate. All of these factors lead to a winding of the duplex helix and antagonize the unwinding of the duplex promoted by transition metal ion binding. Transition metal ions may thus convert the DNA substrate locally to a form in which DNase I can introduce breaks into both strands. In the presence of Mg2+, DNase I introduces single strand nicks into SV40(I), generating exclusively the covalently open, relaxed circular SV40(II) as the initial product of the reaction. In the presence of Mn2+, DNase I generates as initial products a mixture of SV40(II) and unit-length SV40 linear DNA molecules, formed by two nicks in opposite strands at or near the same point in the duplex. These circular SV40(II) molecules consist of two types. A minority class is indistinguishable from the nicked SV40(II) produced by DNase I in the presence of Mg2+. The majority class consists of molecules containing a gap in one of the two strands, the mean length of the gap being 11 nucleotides. The SV40(L) molecules produced in the presence of Mn2+ appear to have single strand extensions at one or both ends. PMID- 6245090 TI - Liposome-mitochondrial inner membrane fusion. Lateral diffusion of integral electron transfer components. PMID- 6245091 TI - Subcellular localization of cyclic GMP-dependent protein kinase and its substrates in vascular smooth muscle. PMID- 6245092 TI - Characterization of polyoma viral DNA sequences in polyoma-induced hamster tumor cell lines. AB - The polyoma (PY) viral DNA sequences present in a series of hamster tumor cell lines were evaluated using the blotting technique of Southern ((1975) J. Mol. Biol. 98, 503-517). Remarkably, no cell line contained an intact distal portion of the early gene region which encodes a portion of the large T antigen. All cell lines examined contained the PY DNA Bum I fragment which contains most of the genetic information encoding PY small and middle T antigens, as well as the origin of viral DNA replication. These results provide an explanation for our previous observation that PY virus-induced hamster tumors do not contain the large species of T antigen. PMID- 6245093 TI - The effect of bacteria on absorbable sutures. AB - In vitro and in vivo experiments were performed on polyglycolic acid and plain catgut sutures to study the effects of bacteria on their rate of degradation. Experiments with Strep, mites, E. coli and Staph. albus in culture showed that the polyglycolic acid sutures degraded faster in broth controls than in a broth containing bacteria as measured by the loss in breaking strength. No difference was observed with the catgut. Polyglycolic acid sutures in subcutaneous sites in rats inoculated with Staph. albus again degrade slower than in similar wounds which were not deliberately infected. With high bacterial counts, the catgut showed the reverse trend although no differences were noted at lower counts. PMID- 6245094 TI - Human osteopetrosis: a histological, ultrastructural, and biochemical study. AB - Histological ultrastructural, and biochemical studies of the tissues of a patient with osteopetrosis were done. The bone contained an increased number of osteoclasts which were characterized ultrastructurally by the absence of ruffled borders and clear zones, hallmarks of actively resorbing osteoclasts. In contrast with normal human bone, tissue collagenase was not detected in osteopetrotic bone cultured in vitro, nor was tissue collagenase activity released when the osteopetrotic bone was incubated with parathyroid hormone. No striking abnormalities of parathyroid hormone or calcitonin were found in the blood or parathyroid and thyroid glands. Except for a slight increase in the extent of lysine hydroxylation of bone collagen, no significant biochemical abnormality of collagen was found. The histological, ultrastructural, and biochemical data support the hypothesis that the basic defect in osteopetrosis is cellular and the osteoclasts, in particular, are abnormal. They appear to be unable to resorb bone and cartilage, and they do not appear to respond to parathyroid hormone in a completely normal way. CLINICAL RELEVANCE: Bone marrow transplantation has produced improvement in both experimental animals and humans and should be actively considered in a child with osteopetrosis who is not thriving. PMID- 6245095 TI - Improvement of gliding function of flexor tendons by topically applied enriched collagen solution. AB - The long flexor tendons of the second, third and fourth toes of 94 chickens were cut and sutured. After operation the birds were divided into three groups. To reduce peritendinous adhesions, an aqueous solution of beta-aminopropionitrile (BAPN) was added to a solution of enriched native collagen (ECS) and applied to the cut tendons of one group; untreated controls and controls treated with collagen solution alone comprised the other groups. Chickens from each group were killed one, two, three, four and five weeks after operation. The results were evaluated both biomechanically and biochemically. It was found that the collagen solution alone had the same effect as the treatment with BAPN. It is suggested that the exogenous collagen present at the site of injury binds the collagenase inhibitor released by tendon cells, thus providing enough active collagenase to control the formation of fibrous adhesions. The inefficiency of BAPN in these experiments might have been due to either inadequate dosage or wrong timing, or both. PMID- 6245096 TI - Clinical experience with proton beam radiation therapy. AB - Our experience with modulated energy proton beams in the definitive treatment of cancer patients indicates that, for the patients accepted, treatment volumes have been smaller and total doses higher than would have obtained for photon techniques alone used in our institution. The reactions of normal tissue have, with very few exceptions, been readily acceptable. The higher radiation doses employed should yield higher tumor control frequencies. Clearly, we cannot assess the efficacy of this modality because of the small number of patients followed for short periods. However, the results are judged by use to warrant intensive evaluation of this modality. PMID- 6245097 TI - Dexamethasone regulates the program of secretory glycoprotein synthesis in hepatoma tissue culture cells. AB - The secretory glycoproteins synthesized by hepatoma tissue culture (HTC) cells were resolved by two-dimensional polyacrylamide gel electrophoresis of media from cells that were grown in the presence of [(3)H]fucose. These cells synthesize and secrete a complex set of fucose-containing glycoproteins. These secretory glycoproteins are distinct from those glycoproteins present in the plasma membrane of HTC cells. Incubation of HTC cells with dexamethasone has a pronounced effect on the quality and quantity (denoted here as the program) of secretory protein synthesis, as assayed by the short-term incorporation of labeled mannose, fucose, or methionine. The synthesis of two mannose- and fucose- containing glycoprotein series, one of 50,000 mol wt and a more heterogeneous series with mol wt of 35,000-50,000, is increased to a high level by the hormone; conversely, the synthesis of other secretory proteins, particularly one with mol wt of 70,000, is decreased or stopped completely. The synthesis of some major secretory proteins is not affected by the hormone. Dexamethasone has less of an effect on the composition of either total cell membrane glycoprotein or plasma membrane glycoprotein. But there is a decrease in the synthesis of a major membrane glycoprotein series with mol wt of 140,000. These effects of dexamethasone are relatively specific to HTC cells. Neither Reuber H-35 cells nor primary cultures of rat hepatocytes show the same response to the steroid. Two variant HTC cell lines, which were selected for their resistance to dexamethasone inhibition of extracellular plasminogen activator activity, respond only partially to the steroid-induced regulation of the secretory and membrane glycoproteins. PMID- 6245098 TI - Light-induced pigment aggregation in cultured fish melanophores: spectral sensitivity and inhibitory effects of theophylline and cyclic adenosine-3',5' monophosphate. AB - About 20% of xiphophorin fish (Xiphophorus maculatus) dermal melanophores which were cultured in monolayer for 5 to 10 days responded to light directly, exhibiting reversible melanosome aggregation within a few minutes. In order to determine the spectral sensitivity for the light-response, absorbance changes due to the light-induced melanosome aggregation were measured on single melanophores in a range of wavelengths from 370 to 550 nm using a recording microspectrophotometer. The melanophores showed maximum sensitivity to a wavelength of about 410 nm and very little to those longer than 500 nm. 10(-4) to 10(-2) M theophylline and 10(-4) M cAMP had inhibitory effects on the light response. PMID- 6245099 TI - Abnormal bone histology in idiopathic hypercalciuria. AB - Bone histology was evaluated in iliac creast biopsies of 15 patients with idiopathic hypercalciuria of the hyperabsorptive type and recurrent calcium oxalate stone formation. The biopsies were studied using quantitative histomorphometric analysis of undecalcified sections and fluorescent microscopy after double tetracycline labeling. Uring calcium and cAMP excretion were measured under basal conditions and after oral administration of calcium phosphate. Absorptive hypercalciuria was defined as a urinary excretion of calcium of more than 15 meq/24 h and/or a urinary ratio of Ca to Cr of more than 0.2, with a fall in the Ca to Cr ratio of more than 40% after the administration of oral cellulose phosphate. Osteoclastic bone resorption was normal or low in all patients and did not show any recognizable correlation with urinary calcium or urinary cAMP. All but one of the patients showed an increase in the fraction of inactive osteoid. Total osteoid was increased in 60% of the patients. Osteoblastic activity was significantly lower in the patient than in the control subjects. The fraction of mineralizing osteoid seams (i.e. seams with a tetracycline double labeling pattern), was diminished in all patients and the mean rate of apposition of bone matrix was decreased. These findings point to a diminished amount of bone matrix produced by individual osteoblasts and to a delay or cessation of terminal (secondary) mineralization of osteoid seams. PMID- 6245100 TI - Cyclic 3',5'-nucleotide phosphodiesterase activities in the thyroid glands of patients with various disorders. AB - Thyroid tissue was found to contain at least least two separable cyclic 3',5' nucleotide phosphodiesterase (cAMP-PDE and cGMP-PDE) activities, as determined by DEAE-cellulose or Sepharose 6B column chromatography. These activities were cAMP- and cGMP-hydrolyzing enzymes. Quantitative differences of cAMP or cGMP hydrolytic activity were observed in tissues from patients with thyroid disorders. Theophylline, modulator protein, and Mg2+ produced similar effects on cAMP or cGMP hydrolytic activity in tissues from patients with a without various thyroid disorders. The mode of the inhibitory effect of cyclic nucleotides on PDE activities in thyroid tissues was competitive, in contrast to the mode seen in other organs. Both cAMP and cGMP hydrolytic activities were elevated in the tissues from patients with hyperthyroidism and thyroid carcinoma compared with the activity in controls. cGMP hydrolysis in hyperthyroidism was 4.4-fold higher than that seen in the controls. The ratio cGMP to cAMP hydrolysis was highest in cases of hyperthyroidism and lowest in cases of thyroid carcinoma, when PDE activities were determined with a substrate concentration of 0.4 microM. Kinetic analysis revealed that higher PDE activity in tissues from patients with hyperthyroidism and thyroid carcinoma was due to an increase in maximal velocity. The apparent Km values for hydrolysis of cyclic nucleotides were similar in normal and pathological thyroid tissues. PMID- 6245101 TI - Endocrine and cardiovascular influences of converting enzyme inhibition with SQ 14225 in hypertensive patients in the supine position and during head-up tilt before and after sodium depletion. PMID- 6245102 TI - Regulation of cyclic nucleotide and prostaglandin formation in normal human thyroid tissue and in autonomous nodules. AB - We have investigated the regulation of the human throid gland based on controls discovered in the dog thyroid gland. TSH and thyroid-stimulating immunoglobulin enhanced cAMP accumulation, which supports the validity of the Sutherland model for the action of TSH on the human thyroid. Iodide inhibited TSH- and thyroid stimulating immunoglobulin-activated cAMP accumulation and this effect was reduced by methimazole, showing that, in this tissue, iodide, through an oxidized derivative, depresses the TSH-cAMP system. Contrary to the hypothesis of a short feedback loop of thyroid hormone, no thyroid effect of T3 or T4 was found. Adrenergic agents (norepinephrine and isoproterenol) enhanced cAMP accumulation; this effect was inhibited by dl-propranolol but not by d-propranolol or phentolamine. This suggests a positive control of the thyroid cAMP system by beta adrenergic receptors. Histamine also increased cAMP accumulation. However, the role of these controls is unknown. Acetylcholine, by a muscarinic type effect, enhanced cGMP accumulation and prostaglandin E2 and prostaglandin F2 alpha release. These effects were mimicked by ionophore A23187 and abolished in a calcium-deprived medium, which suggests that they are secondary to a raised Ca++ influx. The results are summarized in a general working model of human thyroid regulation. These biochemical controls have been compared in normal tissue and autonomous nodules. No evidence of increased sensitivity to TSH of the nodular tissue was found. On the other hand, this tissue was less sensitive to acetylcholine (cGMP accumulation) and more sensitive to norepinephrine (cAMP accumulation). PMID- 6245103 TI - Urinary excretion of cortisol in acromegaly. AB - Free urinary cortisol excretion was measured in 19 patients with acromegaly and 19 matched controls with other pituitary disorders who were comparable with regard to age, sex, and adrenocortical response to ACTH. Excretion of cortisol was significantly higher (P less than 0.01) in the acromegalics (mean, 161 micrograms/24 h or 444 nmol/24 h) compared to the controls (mean, 82 micrograms/24 h or 226 nmol/24 h) normal subjects (mean, 85 micrograms/24 h or 235 nmol/24 h). Seven of the acromegalics had excretion of urinary cortisol exceeding the upper normal limit. The most probable cause is an increased glomerular filtration of cortisol. PMID- 6245104 TI - Oxidation of methionine by human polymorphonuclear leukocytes. AB - Studies of the photosensitized oxidation have demonstrated that photodynamic oxidation of methionine is mediated by singlet oxygen ((1)O(2)). In this study, we demonstrated that phagocytosing human polymorphonuclear leukocytes (PMN), but not resting PMN, oxidized both intracellular and extracellular methionine to methionine sulfoxide. N-ethylmaleimide, which inhibits phagocytosis and cellular metabolism, inhibited the oxidation of methionine. Neutrophils from patients with chronic granulomatous disease did not oxidize methionine even in the presence of phagocytosis. The oxidation of methionine by phagocytosing normal PMN was inhibited by (1)O(2) quenchers, (1.4-diazabicyclo-[2,2,2]-octane, tryptophan, NaN(3)), myeloperoxidase (MPO) inhibitors (NaN(3), KCN) and catalase. In contrast, superoxide dismutase, ethanol, and mannitol had no effect. Furthermore, (1)O(2) quenchers did not interfere with the production of superoxide (O(2) (-)) by phagocytosing PMN. The combination of catalase and SOD did not enhance the inhibition of methionine by phagocytosing PMN. On the other hand, deuterium oxide stimulated the oxidation of methionine by PMN almost 200%.H(2)O(2) at high concentrations oxidized methionine to methionine sulfoxide. However, when similar amounts of H(2)O(2) were added to human PMN, they did not oxidize methionine. In contrast, when H(2)O(2), at concentrations too low to oxidize methionine by itself, was added to the granular fraction, but not the soluble fraction, they oxidized methionine to methionine sulfoxide. The oxidation of methionine by the combination of H(2)O(2) and granular fractions was inhibited by (1)O(2) quenchers and MPO inhibitors, but it was stimulated by deuterium oxide. Removal of chloride anion also prevented the oxidation of methionine by the granular fractions. Our results suggest that the oxidation of methionine by phagocytosing PMN is dependent on the MPO-mediated antimicrobial system (MPO-H(2)O(2)-Cl(-)). They also suggest, but do not prove that the oxidation of methionine is mediated by (1)O(2). Oxidation of methionine may be one of the mechanisms that human PMN damage microorganisms. PMID- 6245105 TI - Increased levels of cyclic adenosine-3',5'-monophosphate in human polymorphonuclear leukocytes after surface stimulation. AB - Levels of cyclic AMP (cAMP) (but not cyclic GMP) in suspensions of human polymorphonuclear leukocytes (PMN) increased promptly after exposure of the cells to stimuli such as the chemotactic peptide N-formyl methionyl leucyl phenylalanine, the immune complex bovine serum albumin/anti-bovine serum albumin and calcium ionophore A23187. cAMP increased rapidly, reaching a maximum of twice the basal level 10--45 s after stimulation; after 2--5 min the amount of cAMP had subsided to basal levels. Elevations in cAMP levels were concurrent with, or followed, membrane hyperpolarization (measured by uptake of the lipophilic cation triphenylmethyl phosphonium) and always preceded lysosomal enzyme release and superoxide anion (O2) production. Elevated cAMP levels could be uncoupled from these later events by removal of extracellular divalent cations, replacement of extracellular Na+ with K+ or choline+, and by use of low concentrations of stimulus; each of these conditions virtually abolished lysosomal enzyme release and O2 generation, while leaving the stimulated elevation of cAMP levels unimpaired. Calcium ionophore A23187 did not provoke membrane hyperpolarization, thus uncoupling changes in membrane potential from changes in cAMP levels. These data suggested that cAMP is not a critical component in the earliest steps of stimulus-secretion coupling. Surface stimulation of cells pretreated with prostaglandins E1 or I2 yielded very high levels of cAMP; these high levels may be an important part of the mechanism by which stable prostaglandins inhibit lysosomal enzyme release and O2 generation. PMID- 6245106 TI - Potection from oxygen toxicity with endotoxin. Role of the endogenous antioxidant enzymes of the lung. AB - Endotoxin treatment of adult rats before hyperoxic exposure significantly increases their survival rate in >95% O(2) (J. Clin. Invest.61: 269, 1978). In this study, we wished to determine: (a) whether endotoxin would protect against O(2) toxicity if it were administered after the animals were already in >95% O(2) for 12-48 h; and (b) the relationship between the endogenous antioxidant enzymes of the lung and the protective effect of endotoxin treatment. Our results showed that adult rats given a single 500 mug/kg dose of endotoxin up to 36 h after the onset of O(2) exposure had significantly increased survival rates and decreased lung fluid accumulation compared to untreated animals in O(2) (P < 0.05). (Survival, 16/49 [untreated rats]; 18/20 [endotoxin at 12 h after the start of O(2) exposure]; 25/26 [endotoxin-24 h]; 15/20 [endotoxin-36 h].)Endotoxin-treated animals in O(2) showed increases in pulmonary superoxide dismutase, catalase, and glutathione peroxidase activities before the usual time of onset of measurable pulmonary edema in untreated animals in O(2). When diethyldithiocarbamate was used to block the superoxide dismutase enzyme rise in the endotoxin-treated rats in O(2), the protective action of endotoxin against pulmonary O(2) toxicity was nullified. In endotoxin-treated, O(2)-exposed mice, there were no lung antioxidant enzyme increases, and no protective effect from O(2) toxicity was achieved. We conclude that, in the rat, a single dose of endotoxin given even 36 h after the onset of hyperoxic exposure results in marked protection against O(2) induced lung damage; and the increased lung antioxidant enzyme activity in the endotoxin-treated rats appears to be an essential component of this protective action. PMID- 6245107 TI - Transferrin receptors on the human placental microvillous membrane. AB - A preparation of microvillous membrane vesicles from human placental syncytiotrophoblast binds transferrin to specific transferrin receptors. Transferrin binding to placental receptors is rapid, saturable, reversible, and specific. Approximately 2.5 X 10(13) receptors are present per milligram of membrane protein; the apparent association constant of transferrin for the placental receptor is 2.2 X 10(7) X M-1. No evidence for removal of iron from transferrin bound to intact membrane receptors was observed in these studies. Nonionic detergent solubilization and partial purification of the microvillous membrane transferrin receptor were carried out with preservation of the functional properties of the receptor. PMID- 6245108 TI - Antibody to the rheumatoid arthritis nuclear antigen. Its relationship to in vivo Epstein-Barr virus infection. AB - Most patients with seropositive rheumatoid arthritis, and a variable but lesser percentage of normal subjects, have precipitating antibodies to a nuclear antigen, rheumatoid arthritis nuclear antigen, present in Epstein-Barr virus infected human B lymphoblastoid cells. We have used a sensitive indirect immunofluorescence assay for antibody to rheumatoid arthritis nuclear antigen in a study of patients with infectious mononucleosis and healthy control subjects. Of 110 sera from normal, college-age cadets, 58 were from individuals without prior Epstein-Barr virus infection, as indicated by the lack of antibody to viral capsid antigen. All of these also lacked activity to rheumatoid arthritis nuclear antigen. 52 sera were positive for antibody to viral capsid antigen, and antibody to rheumatoid arthritis nuclear antigen was present in 26 (50%) of these. In 67 sequential sera from 11 college-age students with infectious mononucleosis who became positive for antibody to rheumatoid arthritis nuclear antigen, only 2 were positive during the 1 mo. Thereafter the incidence and titers increased progressively through the 1st yr after infection. This time-course resembled that for the development of antibody to Epstein-Barr nuclear antigen, another transformation antigen in Epstein-Barr virus-infected B lymphocytes. The development of positivity for both was much later than that of antibody to the structural viral capsid antigen, which in the current study was always positive by 1 wk. Thus, antibody to rheumatoid arthritis nuclear antigen is present in a large proportion of normal individuals and can now be clearly ascribed, from both in vivo and in vitro studies, to prior infection with Epstein-Barr virus. PMID- 6245109 TI - Indirect micro-immunofluorescence test for detecting type-specific antibodies to herpes simplex virus. AB - A rapid indirect micro-immunofluorescence test capable of detecting and differentiating type-specific antibodies to herpes simplex virus is described. The test proved highly sensitive and, in 80 patients with active herpes ocular infection, antibody was detected in 94%. No anti-herpes antibody was detected in a control group of 20 patients with adenovirus infections. Testing of animal sera prepared against herpes simplex virus types 1 and 2 and of human sera from cases of ocular and genital herpes infections showed that the test can differentiate antibodies to the infecting serotypes. Specimens of whole blood, taken by fingerprick, and eye secretions, both collected on cellulose sponges, could be tested by indirect micro-immunofluorescence. Anti-herpes IgG, IgM, and IgA can also be detected. PMID- 6245110 TI - Enterovirus typing by immune electron microscopy using low-speed centrifugation. PMID- 6245111 TI - A technique avoiding carcinogens for the demonstration of myeloperoxidase in blood and bone marrow smears. PMID- 6245112 TI - A quantitative study of the occurrence and distribution of cytoplasmic laminated bodies in the lateral geniculate nucleus of the normal adult cat. AB - The proportion of neurons containing cytoplasmic laminated bodies (CLB) in the dorsal lateral geniculate nucleus (dLGN) of normal cats was determined by using a new method which permitted examination of large areas of this nucleus. Near the medial border of the dLGN (projection of the area centralis) in the A-laminae 30- 60% of the neurons contain CLBs. Within the same region in lamina B only 10--30% of the nerve cells contain CLBs. In the monocular segment (MS) of lamina A 27- 48% of the nerve cells contain CLBs. In the medial interlaminar nucleus (MIN) 25% of the neurons contain CLBs; these cells were distributed throughout the medio lateral extent of the MIN. CLBs were also observed in neurons of the perigeniculate nucleus (PN) and in nerve cells embedded in the fiber sheet separating the dLGN from the pulvinar complex. The distribution of cells containing CLBs is extremely variable in all portions of the dLGN studied. The data presented in this paper indicate that CLB-containing cells in the dLGN may not be X-cells, as has been suggested by LeVay and Ferster ('77) because: (1) the distribution of neurons containing CLBs in lamina A does not match the distribution of X-cells recorded in this lamina; (2) some nerve cells in the MIN contain CLBs but very few X-cells have been found in this region. PMID- 6245113 TI - The blue-gray cystic basal cell epithelioma. AB - We report, in two men, the occurrence of a tiny, dome-shaped, blue-gray cystic nodule of the face. The nodule in both men clinically simulated an eccrine or apocrine hidrocystoma. Histologic examination revealed that both were cystic basal cell epitheliomas. These cases are reported in order to bring this unusual clinical presentation of basal cell epithelioma to the attention of clinicians. PMID- 6245114 TI - Dynamic computed tomography body scanning. AB - The performance of 16 consecutive, 3 sec computed tomographic (CT) scans, after the intravenous administration of a bolus of diatrizoate, was found to be useful in evaluating vascular anatomy and organ perfusion in this study. It also appeared to be useful in lesion detection and in accurately defining the extent of disease. PMID- 6245115 TI - Computed tomography of jugulotympanic paragangliomas. AB - Seven cases of jugulotympanic paragangliomas were studied with computed tomography (CT) and verified by angiography and surgery. All of five glomus jugulare tumors were detected and their extent accurately demonstrated by CT. Two small glomus tympanicum tumors were not convincingly demonstrated. Computed tomography is useful in investigating this neoplasm when it extends beyond the tympanic cavity or is associated with bone destruction. PMID- 6245116 TI - Portal vein tumor thrombus: demonstration by computed tomographic ateriography. PMID- 6245117 TI - Mucopolysaccharidase activity and glycosaminoglycan content in traumatized resorbing deciduous teeth. AB - The periodontal ligaments from traumatized deciduous teeth, while undergoing rapid resorption, were analyzed biochemically for mucopolysaccharidase activity and for total glycosaminoglycan content of dentin and cementum. Enzyme activity was present only in resorbing teeth. A concomitant 65 percent decrease in glycosaminoglycans from these teeth occurred as well. PMID- 6245118 TI - Neurological complications of cryosurgery. AB - Among the few serious complications of cryosurgery are neuropathies. Three cases are reported. Prevention of neuropathy from cryosurgery depends upon awareness of the superficiality of the course of certain peripheral nerves in certain anatomic sites and cautious practice or avoidance of cryosurgery in those sites. PMID- 6245120 TI - Sports hazards. PMID- 6245119 TI - Presenile dementia--a form of Lafora disease. AB - The autopsy findings on a 60-year-old man with progressive disturbances of gait, presenile dementia and incontinence, showed Lafora bodies in numerous ganglion cells of the cerebral cortex and in many nuclei of the brain stem. Histochemical analysis of the Lafora bodies revealed the presence of a polysaccharide-protein complex containing phosphate groups. The case closely resembled the one described by Suzuki et al. It is suggested that this type of presenile dementia may be a presenile form of Lafora disease. PMID- 6245121 TI - Update on drug therapy: III. Metoprolol. PMID- 6245122 TI - I chose a home-office. PMID- 6245123 TI - A comparison of the practice orientations of women and men students at two medical schools. PMID- 6245124 TI - Profile: she always wanted to be a doctor. PMID- 6245125 TI - Abductor pollicis longus transfer for replacement of first dorsal interosseous. AB - One of the tendinous slips of the abductor pollicis longus has been used to replace the first dorsal interosseous. One of the slips which does not insert on the first metacarpal is prolonged by a tendon graft through a subcutaneous tunnel to the insertion of the first dorsal interosseous. This technique has been used in 18 patients who have been followed from 2 to 12 years. All patients had improved stability in pinch, were able to abduct and to flex the index finger independently, and were satisfied with the results. No significant complications were encountered. PMID- 6245126 TI - Anomalous behavior of H-2Kb in immunity to syngeneic SV40 transformed cells: evidence for cytotoxic T cell recognition of H-2/SV40 membrane antigen complexes. PMID- 6245127 TI - Interactions among rheumatoid synovial cells and monocyte-macrophages: production of collagenase-stimulating factor by human monocytes exposed to concanavalin A or immunoglobulin Fc fragments. AB - Adherent synovial cells (ASC) were obtained from minced synovium from patients with rheumatoid arthritis by dissociating the lining cells from the extracellular matrix and dispersing them with proteases. These cells produce high levels of latent collagenase in primary culture. With passage of ASC, collagenase levels decrease but can be stimulated by a soluble factor (MCF) released in vitro from cultured human blood monocyte-macrophages. Monocyte cultures exposed to aggregated immunoglobulin, Fc fragments of immunoglobulin or concanavalin A (Con A) increase production of MCF several-fold more than the control cultures. MCF production by monocytes exposed to Fab fragments does not differ from controls. Although aggregated immunoglobulin, Fc fragments, and Con A stimulate PGE2 synthesis and secretion by human monocytes, the effects on MCF production are not mediated by PGE2 since concentrations of indomethacin that completely block PGE2 production do not inhibit MCF production. These findings of increased production of MCF by monocytes in response to substances that probably exert their effects via surface receptors could be relevant in interpreting the in vivo role of immune complexes in diseases associated with connective tissue destruction. PMID- 6245128 TI - Resistance to fatal central nervous system disease by mouse hepatitis virus, strain JHM. II. Adherent cell-mediated protection. AB - Resistance of SJL/J mice to intracranial inoculation with the JHM strain of mouse hepatitis, a coronavirus, is dependent upon the age of the animals at inoculation. Animals 12 weeks of age or older are resistant, whereas those 6 weeks or younger are uniformly susceptible to viral infection. Spleen cells or thioglycolate elicited peritoneal exudate cells can transfer resistance from 12 week-old to 6-week-old recipients. Removal of the adherent cells from either spleen or peritoneal cells ablated protection. Adherent cells from 12-week-old mice were protective even after depletion of Ia- and Thy-1-bearing cells. Antiviral antibody, thioglycolate injection into 6-week-old animals, and nylon wool-purified T cells were ineffective in mediating resistance. Adherent cells transferred 4 days before virus challenge, but not after challenge, were protective. Thus, there is an age-related change in SJL mice that protects from acute central nervous system disease, which may be due to maturation of a specialized adherent cell population. PMID- 6245129 TI - In vivo responses to inhaled proteins. III. Inhibition of experimental immune complex pneumonitis after suppression of peripheral blood lymphocytes. AB - We have previously shown that inhaled Con A has a powerful enhancing effect on the formation of immune complexes between an inhaled antigen and circulating antibody. Immunohistochemical staining has demonstrated such complexes, together with host complement, in close association with foci of necrotizing destruction of the pulmonary parenchyma. We have postulated that Con A promotes immune complex formation indirectly through polyclonal activation of lymphocytes in the lung. In this paper we test this hypothesis in animals rendered unresponsive to Con A stimulation in vivo by i.v. administration of cholera toxin (CT). Such treatment raised the levels of cAMP in peripheral blood lymphocytes and inhibited their proliferative response to Con A in vitro. CT administration further blocked the local inflammatory response to intradermal injections of Con A, as well as the cell-mediated immune response to intradermal injections of BSA. Although CT failed to block the immune complex-mediated Arthus vasculitis in the skin, it did block production of immune complex pulmonary injury by antigen/mitogen aerosols, as did decomplementation with purified cobra venom factor. These findings support the hypothesis that polyclonal activation of pulmonary lymphocytes promotes immune complex-type alveolitis, possibly by facilitating interactions between humoral antibody and intra-alveolar antigen. PMID- 6245130 TI - The origins of alloreactivity: differentiation of prekiller cells to viral infection results in alloreactive cytolytic T lymphocytes. AB - Mice maintained in our animal colony become primed to Sendai virus. This "environmental" priming is reflected in a shift in prekiller activity from the Ly 123 to Ly 23 T cell set and in increased virus-specific cytolytic activity. This transition is accompanied by the development of cytolytic activity against allogeneic targets (not expressing Sendai antigens). These findings are consistent with the view that continued stimulation of Ly 123 cells by autologous MHC antigens, associated with foreign antigens such as a virus, generate Ly 23 prekiller cells that respond to alloantigens as well as autologous cells infected with the relevant virus. PMID- 6245131 TI - Production of diphtheria antitoxin antibody in Epstein-Barr virus-induced lymphoblastoid cell lines. PMID- 6245132 TI - Chemotactic factor inactivation by myeloperoxidase-mediated oxidation of methionine. PMID- 6245133 TI - Minimal molecular requirements for reactivity of tumor cells with T cells. AB - We have investigated the minimal molecular requirements for T cell recognition of a previously described myeloma tumor (MOPC-315-EL), which reversibly alters its reactivity with T cells. Enucleation of MOPC-315 cells, either sensitive or resistant to reaction with T cells, did not alter the ability of the resulting cytoplasts to elicit or serve as targets for anti-H-2 or anti-Sendai viral cytotoxic T lymphocytes (CTL), despite the fact that there were no detectable differences in serologically defined H-2 or viral antigens on their surface. Likewise, when plasma membranes isolated from sensitive or resistant cells were tested for their ability to elicit anti-H-2 CTL, they retained the phenotype of the cells from which they were isolated. However, solubilized and partially purified H-2 antigens from both sensitive and resistant cells were able to elicit H-2-restricted anti-Sendai virus CTL when incorporated into liposomes with purified viral glycoproteins, and anti-H-2 CTL when incorporated alone into liposomes. These results suggest that a cellular surface component(s) exists that is probably not an H-2K or H-2D gene product and is responsible for the reversible variation in the reactivity of the tumor cells with T cells. PMID- 6245134 TI - Immunoglobulin gene rearrangements in hybridoma cells. PMID- 6245135 TI - The diminished production of arachidonic acid oxygenation products by elicited mouse peritoneal macrophages: possible mechanisms. PMID- 6245136 TI - Deficiency of Epstein-Barr virus (EBV) receptors on B lymphocytes from certain patients with common varied agammaglobulinemia. PMID- 6245137 TI - Development of cell-mediated antiviral immunity and macrophage activation in C3H/HeN mice infected with mouse mammary tumor virus. PMID- 6245138 TI - Adjuvant-induced selective recruitment of specifically reactive lymphocytes: a probable mechanism of adjuvant action. PMID- 6245139 TI - Life-span and size of the trans-membrane channel formed by large doses of complement. AB - To evaluate the life-span and size of trans-membrane channels in complement (C) treated membranes, resealed erythrocyte ghosts containing trapped native protein markers, as well as residual hemoglobin, were treated with anti-Forssman antibody and large doses of guinea pig C. Ovalbumin and hemoglobin were released slowly through the channels so produced, whereas human serum albumin was not. Release of hemoglobin was not blocked by extracellular bovine serum albumin. Release of hemoglobin continued for at least 72 hr at 4 degrees C. Semi-logarithmic plots of ovalbumin or hemoglobin release showed gradual diminution of the rate constant, which indicates slow loss of channels during the experimental period. These experiments demonstrate that the channels produced in erythrocyte ghost membranes by large C doses have a long, although finite, life-span. Their effective diameter is al least 55 A on the basis of ovalbumin and hemoglobin release, and not more than 150 A, since serum albumin was not released. However, an upper limit of 100 A would be more reasonable in light of electronmicroscopic observations by others. These results are compatible with the doughnut model. PMID- 6245140 TI - Induction of cytotoxic T lymphocytes against herpes simplex virus type i: role of accessory cells and amplifying factor. AB - Spleen cells from mice primed with herpes simplex virus type 1 (HSV-1) could be induced to differentiate into cytotoxic T lymphocytes (CTL) by in vitro culture with infectious HSV-1 but not by heat-inactivated virus. Induction of CTL failed to occur if the spleen cells were depleted of adherent cells by passage over columns of nylon wool before culture with virus. The CTL response could be restored by adding normal syngeneic peritoneal cells (PC) or L cell fibroblasts but not by allogeneic PC or BALB/c 3T3 fibroblasts. Thus, the induction of HSV-1 specific CTL was H-2 restricted. The response of HSV-1-stimulated nylon wool depleted spleen cells could also be restored by adding amplifying factor (AF) produced in 24 hr mixed lymphocyte cultures. The addition of AF to nondepleted spleen cells also permitted the generation of CTL with heat-inactivated HSV-1 as a viral stimulant. Our results indicated that induction of a HSV-1 CTL response requires two signals, one provided by virus and a second, presumably nonspecific, by helper T cells. It was suggested that only the helper cells require H-2 restriction and need to be presented virus in the context of a macrophage. PMID- 6245141 TI - Protein phosphorylation in human peripheral blood lymphocytes: mitogen-induced increases in protein phosphorylation in intact lymphocytes. PMID- 6245142 TI - Mediation of macrophage collagenase production by 3'-5' cyclic adenosine monophosphate. AB - The production of collagenase by lipopolysaccharide-(LPS) activated guinea pig macrophages is mediated by prostaglandins (PG) of the E series. After stimulation of guinea pig macrophages with LPS, extracellular PGE levels and cellular cAMP levels are elevated. Indomethacin inhibits not only PG synthesis, but also cAMP and collagenase production in LPS-stimulated macrophage cultures. In these indomethacin-inhibited cultures containing LPS, dibutyryl (dB) cAMP, or cholera toxin can restore macrophage collagenase production but not PG synthesis. Moreover, dBcAMP and cholera toxin enhance collagenase production in LPS activated cultures. Initial activation of the macrophages by an agent such as LPS is a prerequisite for synthesis of collagenase, since in the absence of LPS, dBcAMP or cholera toxin alone are ineffective stimuli. These findings clearly demonstrate a role for PG-induced elevations of cAMP in the production of collagenase by LPS-activated macrophages. PMID- 6245143 TI - From the center for disease control. Epidemiology of pneumococcal serotypes in the United States, 1978--1979. PMID- 6245144 TI - Chemiluminescence by polymorphonuclear leukocytes from patients with active bacterial infection. AB - Polymorphonuclear leukocytes of 18 patients during 19 episodes of active bacterial infection produced increased chemiluminescence (mean +/- standard error [SE], 56.3 +/- 4.4 X 10(3) cpm) when the production was compared to that of 29 uninfected controls (35.3 +/- 2.4 X 10(3) cpm; P less than 0.01). Chemiluminescence production remained increased with persistent infection but fell to the levels of controls with appropriate therapy. Phagocytic uptake as determined with radiolabeled bacteria was increased, and chemotactic responsiveness was markedly enhanced in the patients (mean index +/- SE, 260 +/- 51) when these responses were compared with those of controls (77 +/- 18). Chemiluminescence and chemotactic activity correlated in the patients with bacterial infection (r = 0.76), but one function did not appear to depend upon the intactness of the other. The ratio of cyclic guanosine 3',5'-phosphate to cyclic adenosine 3',5'-hosphate in the polymorphonuclear leukocytes of patients with infections (mean +/- SE, 0.102 +/- 0.0008) was also significantly higher than in controls (0.067 +/- 0.007). These data indicate that the polymorphonuclear leukocytes of the majority of patients with active bacterial infection are in an activated state both functionally and metabolically. PMID- 6245145 TI - Antibiotics in the treatment of gastroenteritis caused by enteropathogenic Escherichia coli. AB - The role of antibiotics in treating endemic infantile diarrhea caused by enteropathogenic Escherichia coli has not been determined. In a controlled study of 49 patients, one group received mecillinam and another group received trimethoprim-sulfamethoxazole. A third group served as control subjects. Serotype O111:B4 dominated. Treatment, as evaluated clinically on the third day, resulted in cure for 79% of those receiving mecillinam, 73% of those receiving trimethoprim-sulfamethoxazole, and 7% of the control subjects. Bacteriologic cure was confirmed in 53%, 53%, and 0, respectively. The statistically significant difference between antibiotic-treated patients and control subjects (P less than 0.001) indicated that antibiotics are an important supplement in the treatment of endemic severe diarrhea caused by enteropathogenic E. coli. PMID- 6245146 TI - Gastroenteritis due to rotavirus in an isolated Pacific island group: an epidemic of 3,439 cases. AB - In the spring of 1964, 3,439 cases of acute gastroenteritis were reported from Truk District, an island group in the mid-Pacific. The causative agent was not identified in laboratory studies performed in that year. Retrospective serologic studies 15 years later with the complement fixation test and the enzyme-linked immunosorbent assay provided serologic evidence that this outbreak was caused by the human rotavirus that was first isolated in 1973. PMID- 6245147 TI - The role of host genetics in the pathogenesis of coxsackievirus infection in the pancreas of mice. AB - The susceptibility of mice to the diabetogenic effect of the M variant of encephalomyocarditis (MEMC) virus is probably inherited as a recissive trait. Three strains of mice that were susceptible to MEMC virus, three strains that were not susceptible to MEMC virus, and three types of F1 hybrid strains were infected with the common human coxsackie virus, group B, type 4 (CB4). They were examined to determine the titer of virus and histochemistry in the pancreas, levels of blood glucose, urinalysis, glucose tolerance, and levels of plasma amylase and insulin. There was a positive correlation between MEMC virus susceptibility (diabetes-prone) and CB4-induced beta cell degranulation with concurrent hyperinsulemia and hypoglycemia. Also, as for MEMC virus, the titer of CB4 in the pancreas was not genotype-dependent. However, there was an inverse relation between destruction of the exocrine pancreas and the effect on the endocrine pancreas. These results suggest that the genetic factors responsible for the effect of MEMC virus on the endocrine pancreas are also responsive to CB4, and the proposed recessive nature of these factors is maintained for both viruses. In contrast, these factors, which are operatively recessive traits for the effect of CB4 on the endocrine pancreas, appear to be expressed as dominant traits with respect to the exocrine pancreas. PMID- 6245148 TI - Development and characteristics of the cellular immune response to infection with varicella-zoster virus. AB - Techniques for assay of in vitro lymphocyte transformation (LTF) were used with varicella-zoster virus (VZV) as the antigen to study the temporal characteristics of the VZV-specific cellular immune response in children with varicella and in normal subjects with a history of the illness. The LTF response in children with only vesicular eruptions was prompt, and individual peak activity was detected within one to two weeks after the onset of illness, followed by a gradual decrease of the activity to lower levels. Patients with a complication of meningoencephalitis showed a marked delay in the development of peak activity. No consistent defference in the development of complement-fixing antibody to VZV was observed in these patients with different clinical manifestations. The LTF response of normal subjects with remote clinical evidence of varicella was characterized by occasional high activity, a finding that suggests reinfection with VZV. These observations provide additional evidence that the specific cellular immune response is heavily involved in the pathogenesis of VZV infection. PMID- 6245149 TI - Inhibition of rhinovirus replication in in organ culture by a potential antiviral drug. AB - The compound 2-amino-1-(isopropyl sulfonyl)-6-benzimidazole phenyl ketone oxime (LY122771-72) at a concentration of 0.2 microgram/ml completely inhibited rhinovirus replication in human embryonic nasal organ cultures, although in the absence of virus the compound did not inhibit ciliary activity when used at a concentration of 25 micrograms/ml. When added 26 hr after infection, the compound stopped rhinovirus production in organ cultures that had already started to release virus. Five rhinovirus types available for infection of volunteers and six recently obtained clinical isolates were shown to be more sensitive to LY122771-72 in tissue culture than the rhinovirus type 31 used in the organ culture experiments. These results suggest that this potential antiviral drgu should be evaluated in humans. PMID- 6245150 TI - Detection of hepatitis A virus in the feces of patients with naturally acquired infections. AB - A prospective study was carried out on 200 patients admitted to Fairfield Hospital, Melbourne, Australia, with acute hepatitis A to determine the frequency with which virus could be detected in their feces. Evidence of infection with hepatitis A virus (HAV) was obtained by detecting IgM specific for HAV in a single serum sample or by demonstrating a rising titer of antibody in paired sera by solid-phase radioimmunoassay. HAV was detected in the feces of 59 of the 200 patients by solid-phase radioimmunoassay and immune electron microscopy. When patients were admitted within one week of the onset of dark urine, 45% were found to be shedding HAV, whereas only 11% of specimens obtained from patients admitted during the second week contained virus. HAV was not detected in fecal specimens collected more than 14 days after the onset of dark urine. These findings suggest that patients admitted to hospital with hepatitis A may still be infectious and that appropriate precautions against fecal contamination should be maintained. PMID- 6245151 TI - Enteroviruses in Vermont, 1969-1978: an important cause of illness throughout the year. AB - Enteroviruses continue to play an important role in both epidemic and sporadic febrile diseases. Of the clinical specimens submitted for diagnosis during a 10 year period (1969-1978) at the Medical Center of Vermont Hospital, Burlington, a wide variety of diseases were associated with the isolation of enteroviruses. Among these diseases were aseptic meningitis, hand-foot-and-mouth disease, diarrhea, pleurodynia, myocarditis, herpangia, and fevers. In 1972 a single enterovirus serotype, coxsackievirus B5, WAS SOLELY RESPONSIBLE FOR EPIDEMIC DISEASE. During the other nine years of the study, a variety of enteroviruses were isolated during epidemics. Although epidemics were always seen during the summer and early fall, enteroviruses which may cause sporadic disease were isolated in each of the 12 months. An awareness by both practicing physicians and health officers not only of the epidemic potential of enteroviruses in summer and fall but also throughout the year will aid in the diagnosis and therapy of these illnesses. PMID- 6245152 TI - Effects of Clostridium difficile toxin on tissue-cultured cells. AB - A partially purified toxin of Clostridium difficile induced similar morphologic changes in three different tissue-cultured mammalian cell lines. The morphologic changes were not associated with biochemical changes indentical to those caused by the enterotoxins of Vibrio cholerae and Escherichia coli. Although the mechanisms responsible for the noncytotoxic morphologic effects remain to be delineated, the toxin appears to exert its effects by directly affecting membrane constituents. PMID- 6245153 TI - Generalized viral illness caused by an intermediate strain of adenovirus (21/H21 + 35). AB - Ten isolates of an antigenically intermediate strain of adenovirus were recovered from eight persons who presented febrile upper respiratory illness, pneumonia, or multisystem disease between November 1976 and August 1978. Six isolates were recovered from four members of an extended family in which the other nine members all had serologic evidence of infection; the other four isolates were epidemiologically unrelated. The isolates were placed in hemagglutination group IB on the basis of results of differential hemagglutination tests. All isolates were identified as adenovirus 21 by serum-neutralization tests and as types 21, 34, or 35 by hemagglutination-inhibition tests with reference rabbit and horse antisera. Conversely, rabbit antiserum to the intermediate strain had high titers of neutralizing antibody to adenovirus 21 and high titers of hemagglutination inhibiting antibody to adenoviruses 21 and 35. The patients' serologic responses were similar. Thus, the isolates were typed as adenovirus 21/H21 + 35 and are the first such intermediate strains recorded. PMID- 6245154 TI - Predictive value of markers of hepatitis virus infection. PMID- 6245155 TI - Protection of guinea pigs inoculated with Tacaribe virus against lethal doses of Junin virus. AB - Guinea pigs were protected against lethal doses of Junin virus by a previous inoculation with Tacaribe virus. Fourteen guinea pigs were infected with 10(6) 50% lethal doses (LD50) of Tacaribe virus and superinfected 45 days later with 10(3) LD50 of Junin virus. Appropriate control groups for both infections were also studied. The replication of Junin virus was impaired, as no virus was isolated from blood and organs of animals killed on days 9 and 11 after infection. High levels of neutralizing antibodies to Tacaribe virus were present by day 45, and no cross-reacting neutralizing antibodies to Junin virus were detected. However, three days after challenge with Junin virus, a typical secondary immune response to this virus was established. From these results it was concluded that the protection observed was mainly due to a specific immune response that was triggered by the Junin virus but primed by Tacaribe virus, which is antigenically similar to Junin virus. PMID- 6245156 TI - Age-dependent pathogenicity of group B coxsackieviruses in Swiss-Webster mice: infectivity for myocardium and pancreas. AB - Coxsackieviruses B1-B4 were inoculated intraperitoneally into 48-hr-old, 14-day old, and three- to five-month-old Swiss-Webster mice. Immediate death occurred only among mice less than 48 hr old, which died from fulminant encephalitis. Older mice usually survived. Myocarditis ensued in mice less than 48 hr old that were infected with coxsackieviruses B1 and B4. Several of the surviving mice developed left ventricular aneurysms, which resulted from transmural necrotizing myocarditis. In this group (coxsackieviruses B1 and B4), pathologic changes in the heart were synchronous with maximal cardiac titers of virus. Fourteen-day-old mice infected with coxsackieviruses B2 and B3 developed nontransmural necrotizing myocarditis in which maximal pathologic changes followed peak cardiac titers of virus by several days, whereas three- to five-month-old mice infected with coxsackieviruses B1, B2, B3, or B4 showed maximal susceptibility to destructive lesions in the exocrine glandular pancreas. Therefore, specific susceptibilities to infection with coxsackieviruses group B vary with age of the mouse, virus type (and strain), and organ. PMID- 6245157 TI - Stimulation of cyclic 3':5'-guanosine monophosphate levels in rat spleen cells by lipopolysaccharide preparations. AB - LPS greatly increases cGMP in rat fetal liver cells without affecting cAMP. The present experiments were undertaken to determine whether this effect occurs in an adult tissue, which might be exposed to LPS in vivo. Therefore cyclic nucleotides were measured in adult male rat spleen cells incubated in vitro in the presence or absence of LPS. A clear cGMP elevation was found in cultures treated with LPS. This was first evident at 2 hr and persisted for 4 hr. In contrast, cAMP was unaffected by LPS even in the presence of the phosphodiesterase inhibitor, MIX. CGMP rose progressively with LPS doses ranging from 0.8 to 20 ng, and addition of MIX potentiated the cGMP stimulatory effect. Several LPS concentrates prepared by different techniques and LPS exposed to vigorous heat treatment exhibited cGMP activity, whereas absorption of LPS with Limulus lysate abolished the cGMP response. Thus LPS increases cGMP in rat spleen cells in a dose-and time dependent manner without affecting cAMP. Although the significance of this cGMP increase is unknown, its occurrence in spleen cells (a tissue likely to come in contact with LPS in vivo), its production by very small quantities of LPS, and the delayed but persistent nature of the effect (analogous to the aciton of cholera toxin on cAMP) are all consistent with an important role for cGMP in the action of LPS on cells. PMID- 6245158 TI - Inhibition of polymorphonuclear leukocyte adherence by prostacyclin. AB - The adherence of human PMNs to nylon fibers or endothelial cells is inhibited by exposure in vitro of the phagocytic cells to PGl2. The impaired adherence is transient and correlates with a rise in intracellular levels of cyclic AMP. Similarly, stimulation of human endothelial cells with sodium arachidonate, a precursor of PGl2, leads to impaired PMN adherence. On the other hand, PGl2 failed to alter O2- release and the bactericidal capacity of the PMNs. These findings suggest that PGl2 may play a role in regulating PMN adhesiveness to endothelial cells without compromising host defense. PMID- 6245159 TI - Effect of adrenocorticotrophin on intracellular cholesterol transport. PMID- 6245160 TI - An improved methodology for the extraction and partial purification of porcine hypothalamic corticotrophin releasing factor. AB - In most previous reports material with corticotrophin releasing factor (CRF) activity has been obtained from hypothalami after extraction with dilute aqueous acid. Such conditions allow substantial proteolytic degradation. By adopting conditions designed to precipitate proteases and by using information on the nature of CRF gained from earlier studies, rapid large scale extraction and partial purification of porcine hypothalamic CRF in high yield was achieved. After extraction with 0.2 m-HCl; acetone (1:1, v/v), centrifugation and ultrafiltration, considerable preliminary purification of the CRF activity was achieved by adsorption onto carboxymethylcellulose and subsequent elution at increased salt concentration. Following ion-exchange chromatography of the extract on carboxymethylcellulose, CRF activity was obtained in good yield (minimal effective dose of about 1-2 micrograms/ml) for ACTH release in an in vitro CRF bioassay utilizing a coupled isolated pituitary cell-adrenal cell system. The data indicated that the previously reported heterogeneous corticotrophin releasing factors of low activity may be a consequence of proteolytic degradation. PMID- 6245162 TI - Comparison of slow larval and fast adult muscle innervated by the same motor neurone. AB - 1. Muscles innervated by an identified set of motor neurones were compared between larval and adult stages. 2. The structure of the larval muscle is typically tonic: long sarcomeres, irregular Z-bands, and 10-12 thin filaments around each thick filament. The structure of the adult muscle is phasic: 3-4 micrometers sarcomeres, regular Z-bands, 6-8 thin filaments around each thick filament, and large mitochondrial volume. 3. The tensions produced by these muscles were correspondingly different. The larval twitch was about 7 times slower and the tetanus/twitch ratio 10 times greater than those of the adult. 4. No structural or physiological differences were observed in the neuromuscular junctions of the two stages. 5. The relatively unchanging functional relationship of a single motor neurone with two different muscle fibre types during two developmental stages is compared with the converse situation in which it has been reported that implantation of a different type of motor nerve into a muscle modifies contractile properties. PMID- 6245161 TI - Properties of insulin and glucagon receptors on sheep hepatocytes: a comparison of hormone binding and plasma hormones and metabolites in lactating and non lactating ewes. AB - A method is described for the isolation of viable hepatocytes from sheep liver. The characteristics of insulin and glucagon binding to the cells were investigated by the use of mono-iodinated hormone, and from these data the optimum in-vitro incubation conditions for hormone-receptor binding were established. Glucagon and insulin receptors were examined in relation to plasma concentrations of hormones and metabolites in non-mated, and 20- and 50-day lactating ewes (six animals/group). Measurements of insulin, growth hormone and non-esterified fatty acids in the circulation, together with a fall in body weight, suggested that a peak lactation (20 days) the ewes were in energy-deficit and were mobilizing body tissue. The percentage binding of insulin was higher in hepatocytes after 50 days of lactation when compared with that in both the unmated (P less than 0.05) and 20 day-lactating animals. No changes in insulin binding were found between the unmated and 20-day-lactating groups. Glucagon binding was reduced in the 20- (P less than 0.02) and increased in the 50-day lactating group (P less than 0.001) when compared with the unmated control animals. The binding of glucagon was higher at 50 days as compared with 20 days of lactation (P less than 0.001). The changes in insulin binding resulted primarily from altered receptor numbers whereas changes in the binding of glucagon were due to alterations in both receptor numbers and affinity. Our results indicated that the binding of insulin and glucagon to isolated hepatocytes was altered during lactation in sheep and that these changes might modulate the sensitivity of the cells to the actions of the hormones. PMID- 6245163 TI - Electrical interactions between the giant axons of a polychaete worm (Sabella penicillus L.). AB - Intracellular recordings demonstrated a transfer of impulses between the paired giant axons of Sabella, apparently along narrow axonal processes contained within the paired commissures which link the nerve cords in each segment of the body. This transfer appears not to be achieved by chemical transmission, as has been previously supposed. This is indicated by the spread of depolarizing and hyperpolarizing voltage changes between the giant axons, the lack of effects of changes in the concentrations of external divalent cations on impulse transmission and by the effects of hyperpolarization in reducing the amplitude of the depolarizing potential which precedes the action potentials in the follower axon. The ten-to-one attenuation of electronic potentials between the giant axons argues against the possibility of an exclusively passive spread of potential along the axonal processes which link the axons. Observation of impulse traffic within the nerve cord commissures indicates, on the other hand, that transmission is achieved by conduction of action potentials along the axonal processes which link the giant axons. At least four pairs of intact commissures are necessary for inter-axonal transmission, the overall density of current injected at multiple sites on the follower axon being, it is presumed, sufficient to overcome the reduction in safety factor imposed by the geometry of the system in the region where axonal processes join the giant axons. The segmental transmission between the giant axons ensures effective synchronization of impulse traffic initiated in any region of the body and, thus, co-ordination of muscular contraction, during rapid withdrawal responses of the worm. PMID- 6245164 TI - Involvement of cyclic GMP in the release of stereotyped behaviour patterns in moths by a peptide hormone. AB - A peptide hormone, the eclosion hormone, triggers two behavioural patterns--the pre-eclosion and eclosion patterns--when injected into pharate silkmoths. Injection of cyclic nucleotides caused the same behavioural responses with cGMP being 10 to 100 times more potent than cAMP. Exogenous cGMP also acted directly on the isolated nervous system to evoke the characteristic motor programmes. Protection of endogenous cyclic nucleotides by pretreatment of moths with a phosphodiesterase inhibitor, theophylline, markedly enhanced the sensitivity of the moths to the hormone. Injection of partially purified hormone preparations was followed by an increase in nervous system cGMP but not cAMP. The increase preceded the behavioural effectiveness of each dose was correlated with its ability to cause a cGMP increase. It was concluded that the behavioural effects of the eclosion hormone are mediated through an increase in cGMP in the nervous system. PMID- 6245165 TI - The response of the kidney of the freshwater rainbow trout to true metabolic acidosis. AB - Infusion of lactic acid into the bloodstream of trout produced a short-lived depression of blood pH and a long-lasting elevation of blood lactate. The lactate injected was distributed in a volume of 198 ml/kg. Renal excretion of lactate anion and total acid increased by approximately equal amounts during the period of high blood lactate levels, but total renal loss over 72 h accounted for only 2% of the lactate load and 6% of the proton load. Comparable differences in the time courses of blood lactate and pH changes occurred when lactacidosis was induced endogenously by normocapnic hypoxia. The immediate response of the kidney was similar to that with lactic acid infusion, but there was a long-lasting (12 72 + h) elevation of urinary acid efflux that was not associated with lactate excretion. Following hypoxia, renal excretion over 72 h accounted for 1% of the estimated lactate load and 12-25% of the proton load. A renal lactate threshold of 4-10 muequiv/ml prevents significant urinary lactate excretion. The response of the trout kidney to true metabolic acidosis is similar to that of the mammalian kidney. PMID- 6245166 TI - Membrane currents of pawn mutants of the pwA group in Paramecium tetraurelia. AB - Membrane currents were recorded from the wild type and two pawn mutants of the pwA complementation group in Paramecium tetraurelia under a voltage clamp. Most currents are not changed by the mutations. Transient inward currents of a leaky mutant, pwA132, upon step depolarizations are less than those in the wild type. The inward transient is completely lacking in a non-leaky mutant, pwA500. The time course of the residual inward currents in the leaky mutant is not significantly different from that of wild type. The voltage sensitivity of the Ca channels in the leaky mutant is also similar to that of wild type. The inward currents upon membrane hyperpolarizations in the mutants show normal characteristics in the presence or absence of external K+. With sufficiently large, prolonged depolarization, outward currents progressively develop in the wild type but decay in the mutants. The simplest conclusion we can draw is that the pwA mutations reduce the number of functional Ca channels but do not change the channel characteristics. From the conductance measurements, 45% of the Ca channels remain in the leaky mutant pwA132, and none remain in the non-leaky mutant pwA500. By subtracting the outward currents of pwA500 from the slow and prolonged outward currents of the wild type, we have tentatively separated a Ca induced K+ current from the voltage-dependent K+ current. The time courses of these two currents differ by two orders of magnitude. PMID- 6245167 TI - Ba2+ influx measures the duration of membrane excitation in Paramecium. AB - We have developed an assay for the duration of membrane excitation in Paramecium tetraurelia by tracing the influx of 133Ba2+. This assay is performed at physiological temperatures and in physiological solutions. Ba2+ enters the paramecia through the Ca channels, since mutants defective in Ca channels show no significant Ba2+ influx. Ba2+ enters only when the Ca channels are opened during excitation which can be triggered by Na+ or Ba2+ itself. The ionic species and relative concentrations determine the duration of the action potentials and hence the duration of spinning or backward swimming. The longer the average period of excitation, the larger the Ba2+ influx. In a Ba-Ca solution the cells spend 30% of their time in the excited state. The rate of Ba2+ entry into the paramecia in that state is 1.3 mM/min. Ba2+ influx occurs over a 50-fold range of Ba2+ concentration. There is very little Ba2+ efflux. The fate of the entered Ba2+, the consequences of the large and rapid influx, the advantages and drawbacks of the Ba2+ influx assay, and the possible use of the assay for Ca channel function in cell-free preparations are discussed. PMID- 6245168 TI - Nuclear changes in cells infected with parapoxviruses stomatitis papulosa and orf: an in vivo and in vitro ultrastructural study. AB - During ultrahistological investigations of naturally occurring cases of stomatitis papulosa in cattle and Orf in sheep, nuclear changes consisting of aggregations of double membrane-containing tubular structures (outer diam. 100 to 130 nm, inner diam. 50 to 65 nm) and filamentous material were observed. These changes could be reproduced in vitro after infection of bovine (BEL) and ovine (OEL) embryonic lung cell cultures with stomatitis papulosa virus and Orf virus isolates. Nuclear tubules were mostly associated with stomatitis papulosa, whereas filaments were regularly detected in Orf virus infections in vivo. Stomatitis papulosa virus also induced nuclear tubules in vitro in the two cell culture types employed, whereas tubular structures after Orf virus infection only developed in ovine embryonic lung cell cultures in addition to filamentous structures. Orf virus infection of BEL cell cultures induced the formation of filaments. Fluorescent antibody staining revealed parapoxvirus-specific antigens only in the cytoplasm of infected cells. PMID- 6245169 TI - A lymphoblastoid response of human foetal lymphocytes to ultraviolet-irradiated herpes simplex virus. AB - Cultures of foetal lymphocytes were exposed to u.v.-irradiated herpes simplex virus (HSV). The cells responded with increased 6-3H-thymidine incorporation, the formation of clumps of enlarged lymphoblastoid cells and cell division. This response was first detected 3 to 4 days after exposure to virus material and was shown to be virus-dose dependent. The ability to stimulate foetal cells was considerably more u.v. resistant than infectivity. Two isolates of HSV type 2 (4663 and 37174), which had a high "transforming" ability, produced large numbers of non-infectious particles (particle: infectivity ratios in excess of 10(4)). The cells, which responded to u.v.-irradiated HSV with blastoid transformation, were associated with the non-E-rosetting (T-cell-depleted) subpopulation. PMID- 6245170 TI - Isolation of herpes simplex virus from the skin of clinically normal mice during latent infection. AB - Herpes simplex virus (HSV) was isolated from the ears of clinically normal, latently infected mice by culturing the skin in vitro. The results are discussed with reference to current theories of HSV latency. PMID- 6245171 TI - Synthesis of virus DNA and polypeptides by temperature-sensitive mutants of rabbitpox virus. AB - Eighteen temperature-sensitive (ts) mutants of rabbitpox virus were examined for defects in synthesis of DNA and protein. Two mutants (ts-3 and ts-16) were defective in DNA synthesis (DNA-), since both incorporated significantly less than wild-type amounts of labelled thymidine into acid-precipitable material when infected cells were incubated at the restrictive temperature. Both these mutants gave only the 'early' class of virus polypeptides when infected cell extracts were examined by SDS--polyacrylamide slab gel electrophoresis following incubation at 40 degrees C. Nine of the remaining sixteen DNA+ ts mutants (ts-1, ts-2, ts-6, ts-12, ts-15, ts-17, ts-31, ts-32 and ts-33) synthesized wild-type levels of most virus polypeptides at 40 degrees C; six DNA+ ts mutants (ts-7, ts 8, ts-9, ts-11, ts-23 and ts-24) were defective in the post-translational cleavage of the polypeptides involved in membrane stabilization and particle assembly; one DNA+ ts mutant (ts-14) synthesized only the 'early' class of virus polypeptides, implying that either replicated DNA was not fully functional or that a specific early function was required for late transcription. PMID- 6245172 TI - Detection of avian oncovirus group-specific antigens by the enzyme-linked immunosorbent assay. AB - A three-step sandwich enzyme-linked immunosorbent assay was developed for the detection of avian oncovirus group-specific (gs) antigens. The assay procedure was to coat the wells of microtitre plates with hamster anti-gs IgG, react with crude or purified antigen and finally with hamster anti-gs IgG linked to horseradish peroxidase. The sensitivity was 8 picograms (pg) of input avian myeloblastosis virus (AMV) protein, with negligible background. As the ELISA takes less than 2 h to perform, large-scale screening for infected birds is feasible. A blocking assay was also developed for detecting anti-gs antibodies by adding unlabelled antiserrum after the antigen step. PMID- 6245173 TI - Some characteristics of an early protein (ICP 22) synthesized in cells infected with herpes simplex virus. AB - In Vero cells incubated at 40 degrees C or treated with azetidine at 37 degrees C, synthesis of a polypeptide ('C') of apparent mol. wt. 66000 was stimulated. It was not phosphorylated and was found in the cytoplasmic fraction of cell lysates. In cells infected with herpes simplex virus type 1 (HSV-1) in the presence of azetidine, synthesis of cellular proteins, including polypeptide C, was suppressed and infected cell polypeptides ICP 4, 0, 22 and 27 (apparent mol. wt. 170000, 120000, 75000 and 60000, respectively) were made. All were phosphorylated and accumulated in the nucleus. Messenger RNA for the same four polypeptides was made in cells infected in the presence of cycloheximide. Thus, ICP 22 is distinct from cellular polypeptide C and is probably a virus-specific alpha polypeptide, although it differs from alpha ICP 4, 0 and 27 in that its rate of synthesis does not decline rapidly when later polypeptides are produced. It is modified after synthesis in at least two steps, the second of which may require a later virus specific polypeptide. In cells infected with HSV-2 the synthesis of a polypeptide analogous to ICP 22 could not be detected. PMID- 6245174 TI - Alterations in virus protein synthesis and capsid production in infection with DI particles of herpesvirus. AB - High multiplicity, undiluted passage of equine herpesvirus type 1 (EHV-1) in L-M cells resulted in the rapid production of virus particles whose genome was genetically less complex, contained more reiterated DNA sequences and exhibited a greater buoyant density (rho = 1.724 g/ml) than the DNA (rho = 1.716 g/ml) of standard virus. These data and the finding that these particles inhibited the replication of standard virus in interference assays confirmed that these were defective interfering (DI) particles (Henry et al. 1979). Additional evidence for this has been obtained from the pattern of cyclic fluctuation in infectious virus titre through 17 serial passages as well as from the pronounced variation in the particle to plaque ratio for each passage. Total particle production was markedly reduced in cells infected with virus preparations containing DI particles and quantification of major cell-associated EHV-1 capsid species by electron microscopy and analysis in Renografin density gradients indicated that this reduction occurred at the level of capsid assembly. Although total capsid production was reduced in cells infected with DI particle preparations, the synthesis of I (immature) capsids increased relative to that of L (empty) capsids and these alterations in the assembly of capsid species could be related to changes in the synthesis of capsid proteins. In cells infected with EHV-1 preparations rich in DI particles, the synthesis of major capsid protein 150000 was greatly reduced, whereas core protein 46000, a major component of I capsids, was overproduced as compared to standard virus infection. Capsids produced in cells infected with virus preparations rich in DI particles were identical in polypeptide composition to those made in standard virus infection. PMID- 6245175 TI - Two particle types of avian infectious bronchitis virus. AB - Two distinct types of avian infectious bronchitis virus (IBV) particles were isolated on sucrose density gradients. The higher density particles banded at 1.18 g/ml, had typical coronavirus morphology and contained all the structural polypeptides and a complete genome. The less dense particles of density 1.13 g/ml appeared to have typical coronavirus morphology, although they were much more flattened than the more dense particles. Furthermore, these particles lacked the ribonucleoprotein polypeptide and the genome, although all the other polypeptides were present in the same amounts as in the denser particles. PMID- 6245176 TI - Symmetrical arrangement of the heterologous regions of rabbit poxvirus and vaccinia virus DNA. AB - Cleavage sites for the restriction endonucleases EcoRI, KpnI and XhoI were mapped on rabbit poxvirus and vaccinia virus DNA. These physical maps were used to analyse the structural variations between the two DNAs. Two specific heterologous regions, symmetrically arranged at each end of the genomes, have been identified. Region 1, representing the exterior part of the terminal repetition, appears to contain unrelated sequences in each DNA and accounts for the difference in length of the two genomes. Region 2, separated from region 1 by a conserved part of the terminal repetition, is located at the transition from repeated to unique DNA sequences. Its overall length of about 4 megadaltons is well conserved and it contains individual DNA-specific as well as conserved restriction sites. The major central part of the genomes (over 100 megadaltons) contains very few, widely dispersed restriction site variations. PMID- 6245177 TI - The prevalence of naturally occurring antibodies to human syncytial virus in East African populations. AB - A seroepidemiological study of naturally occurring antibodies to the human syncytial virus has been carried out by means of an indirect immunofluorescence test on 639 East Africans, consisting of 493 normal Ugandans, 66 Kenyan patients with nasopharyngeal carcinoma (NPC), and 80 Kenyan and Tanzanian patients with various other tumours or non-cancerous conditions. It was found that 3.4% of the normal individuals had antibodies to the virus and serial serum samples were available from 14 of these, permitting the study of antibody class in seroconversion and antibody persistence. As in an earlier survey, a significantly higher incidence of antibodies was found amongst NPC patients. Blocking and indirect immunofluorescence test with simian foamy viruses (SFV) showed some cross-reactivity between SFV 6 and the human syncytial virus, but not identity. The results are discussed in relation to the very real occurrence of natural infection by human syncytial virus in certain geographical regions. PMID- 6245178 TI - Biological and molecular biological characterization of the virus progeny from transformed clones MuSV-124 and MuSV-349: evidence for MuLV-specific nucleotide sequences in the MoMuSV size class of RNA from MoMuSV-124. AB - The genetic information of MoMuSV-349 and MoMuSV-124, two clones of productively transformed TB cells, was distributed between two size classes of RNA (mol. wt. 2.9 x 10(6)) in the proportions of 5:1. Some preparations of MoMuSV-124 lacked the large RNA. The virions produced by both clones also contained all the nucleotide sequences of Moloney leukaemia virus and the ratio of MuSV:MuLV produced by the two clones differed markedly. The distribution of the sequences specific for Moloney murine leukaemia virus (MoMuLV) between the two size classes of RNA was studied using molecular hybridization to DNA probes complementary to and representative of: (i) the Moloney murine sarcoma virus (MoMuSV) RNA genome (mol. wt. 1.9 x 10(6)); (ii) those nucleotide sequences shared by MoMuSV and MoMuLV; (iii) nucleotide sequences specific for MoMuSV; (iv) nucleotide sequences specific for MoMuLV. The only detectable Moloney leukaemia virus-specific nucleotide sequences present in MoMuSV-124 virions were in the RNA of mol. wt. 1.9 x 10(6), whereas these sequences were detected in the RNA of mol. wt. 2.9 x 10(6) isolated from MoMuSV-349 virions. The biological properties of the replicating information in MoMuSV-124 suggest that, consistent with the small size of RNA, it is defective. whereas MoMuSV-349 produces virions containing an intact MoMuLV genome, competent for replication. PMID- 6245179 TI - Preparative isoelectric focusing of poliovirus polypeptides in urea-sucrose gradients. AB - Isoelectric focusing in urea using small density gradient columns for dissociated poliovirus resulted in a complete separation of the four virus polypeptides. Identification and purity of VP1, 2, 3 and 4 was shown by SDS-polyacrylamide gel electrophoresis. The isoelectric points were determined and compared with the values obtained in gels. The recovery of the individual polypeptides was about 80%. Up to 500 microgram of poliovirus per tube could thus be separated in a one step procedure giving pure and SDS-free poliovirus polypeptides. PMID- 6245180 TI - Differential host ranges for in vitro infectivity of mouse mammary tumour viruses. AB - Host-range variants of mouse mammary tumour viruses (MMTVs) have previously been shown to productively infect cells of several species in vitro (Howard & Schlom, 1978). We report here that cell lines have been identified which exhibit differential restriction for replication of different MMTV variants. In addition, a cell line has been identified that changes as a function of passage in culture from being permissive to being restrictive to infection with MMTVs. MMTVs propagated in both murine and non-murine cells retained their antigenic reactivities in a group-specific radioimmunoassay for MMTVs and demonstrated no evidence for the presence of type-C viruses as determined by a variety of techniques. These studies thus establish in vitro cell substrate tropisms that can be used to differentiate between MMTVs. PMID- 6245181 TI - Multiplication of human rotavirus in cultured cells: an electron microscopic study. AB - Human rotaviruses were capable of efficient multiplication in LLC-MK2 cells when the inoculum was pre-treated with trypsin, centrifuged on to the cell monolayer and the infected cells maintained in a medium containing trypsin. However, not all of the human rotavirus isolates used to infect cells resulted in efficient virus production. The ability of human isolates to multiply in cultured cells was studied by direct observation of virus in the electron microscope, by radioactive labelling with 3H-uridine of the newly synthesized virus and by electron microscopic examination of thin sectioned infected cells. With one of the specimens used (F-617) only 5 to 10% of the cells showed evidence of virus multiplication, with the great majority of the infected cells showing numerous complete (double-capsid) virus particles scattered in the cytoplasm. When cells were inoculated with another human specimen (SIB-I), infected cells were more abundant, reaching a maximum of 60%; however, a variety of particle types, probably representing different subviral structures or different steps of rotavirus morphogenesis, were commonly observed. The presence of these aberrant or incomplete virus structures may represent a manifestation of the defectiveness of this virus and may explain the difficulties encountered in its serial passage. PMID- 6245182 TI - Role of cytotoxic T lymphocytes in murine cytomegalovirus infection. AB - Cell-mediated immunity is important in host control of CMV infection. A chromium release microcytoxicity assay was used to evaluate the role of cytotoxic T lymphocytes (CTL) in murine CMV infection. Within a few days after intranasal inoculation virus was detected in cultures of buffy-coat, spleens, anterior cervical lymph nodes and salivary glands. CTL were first detected on day 5 post infection in spleen and peripheral blood, and on day 6 in anterior cervical nodes. The course of the CTL response approximated to that of virus titres during the acute phase of infection in the spleen and blood. The findings indicate that CTL are distributed to infected tissues and appear to be important during the acute, viraemic phase of infection. PMID- 6245183 TI - Persistent paramyxovirus infections and behaviour of beta-adrenergic receptors in C-6 rat glioma cells. AB - This paper describes the influence of persistent infections of C-6 rat glioma cells by paramyxoviruses [virus of subacute sclerosing panencephalitis (SSPE) and canine distemper (CDV)] on the cellular beta-adrenergic membrane receptors. The number and binding properties of the beta-adrenergic receptors of the paramyxovirus-infected cells were measured by 3H-dihydroalprenolol binding studies and compared with those of the uninfected C-6 cells. In the case of SSPE virus neither changes in number nor binding properties of beta-adrenergic receptors could be observed, whereas in the case of CDV persistence the number of beta-adrenergic receptors was reduced to about 50%, without an apparent influence on the binding constant for the ligand to the receptors. PMID- 6245184 TI - Isolation of a new strain of cytomegalovirus from explanted normal skin. AB - Forty-three fibroblast cell line were initiated from normal skin biopsies. One cell line from a patient with Charcot--Marie--Tooth disease (CMT) spontaneously developed c.p.e. suggestive of cytomegalovirus (CMV). Characterization of the virus showed it to be a new strain of CMV and the results suggested that skin fibroblasts from CMT patients may carry latent CMV. PMID- 6245185 TI - Early changes of muscle mitochondria in Duchenne dystrophy. Partition and activity of mitochondrial enzymes in fractionated muscle of unaffected boys and adults and patients. AB - (1) Biopsies from the gastrocnemius muscle of patients with Duchenne dystrophy were partitioned into a myofibrillar plus nuclear fraction, a mitochondrial fraction and a supernatant fraction. The fractions were assayed for mitochondrial enzymes and protein, in order to obtain information about the integrity of mitochondrial structure and function. Muscles from boys and adults without neuromuscular disease were treated likewise. (2) In adults, muscle possesses a significantly higher specific activity (on protein basis) of monoamine oxidase and rotenone-insenitive NADH-cytochrome c reductase (RINCR) than in boys. In childhood, monoamine oxidase activity increases with age. At the age of 5 yr, the specific activity is 50% of the adult value. RINCR activity is constant in childhood. With adolescence it increases from 20 +/- 2 (SEM) to 35 +/- 6 mumoles cytochrome c reduced per min per g protein, and it remains at this level. Palmitoyl-CoA synthetase activity remains constant with age. (3) In Duchenne dystrophy the extractable protein content from muscle is decreased to 75%. The specific activities of the matrix enzymes propionyl-CoA carboxylase and glutamate dehydrogenase are 1.8 and 2.8 times increased, the inner membrane enzyme cytochrome c oxidase is 2.8 times increased, the inner membrane enzyme cytochrome c oxidase is 2.8 times increased. Of the outer membrane enzymes RINCR is 2.0 times increased, while palmitoyl-CoA synthetase is not changed in acitivity. In Duchenne dystrophy monoamine oxidase activity also increases with age. In part this may be due to mitochondria from adipose tissue and macrophages, which are increasingly present in older patients. The specific activities of enzymes with a predominant cytosolic localisation, creatine kinase and adenylate kinase, are increased by a factor of 1.5 and 1.7. (4) The subcellular distribution of the studied enzymes in human skeletal muscle was found to be similar as in animal studies. In mitochondrial fractions from Duchenne patients the recoveries of the following enzymes are decreased: glutamate dehydrogenase (from 25 to 9%), creatine kinase (1.1-0.66%), adenylate kinase (0.44-0.22%), hexokinase (7.1 2.7%), monoamine oxidase (36-21%), RINCR (30-17%), and palmitoyl-CoA synthetase (40-21%). The recoveries of last 3 mitochondrial outer membrane enzymes in the supernatant fractions are correspondingly increased. These results indicate an increased fragility of the mitochondrial membranes in dystrophic muscles. (5) The reported changes are clearly evident in a one-year-old patient, which indicates that the mitochondria are involved early in the disease process. PMID- 6245186 TI - Definition of a cell clone with astroglial characteristics derived from a chemically induced rabbit brain glioma. AB - Three-month-old rabbits were started on a fortnightly schedule of intravenous injections of N-methyl-N-nitrosourea. All but two of the central nervous system tumors induced in this manner were propagated in culture as permanent cell lines. On the 76RB-G-414-H line established from a grade 2 astrocytoma of this series of neoplasms, a cloning procedure was carried out using a laser microbeam. The clonal line originated in this way has been maintained in long-term culture and given the 76/RB-G-414-H-C designation. The cells of the clone display invariably a bipolar or multipolar configuration with long processes. Intermediate filaments are common and even abundant in some cells. Positivity for S-100 and GFA proteins is a regular finding in these cells. In addition, dibutyryl cyclic adenosine monophosphate treatment reduces cell division and stimulates cell process formation of these cells. Thus, it appears that we succeeded in establishing in vitro and maintaining in long-term culture a clone of tumor cells with astrocytic characteristics. PMID- 6245187 TI - Spin label and biochemical studies of erythrocyte membranes in Alzheimer's disease. AB - Electron spin resonance, enzymatic, and SDS-polyacrylamide gel electrophoretic investigations of erythrocyte membranes from patients with Alzheimer's disease were performed. Alterations in the physical state of membrane proteins in Alzheimer's disease erythrocytes were found by spin labeling studies. However, no alterations in membrane lipid fluidity or in the activities of membrane-bound sodium plus potassium-stimulated, magnesium-dependent adenosine triphosphatase or acetylcholinesterase could be demonstrated. Also, no changes in staining profiles of AD erythrocyte membrane proteins subjected to electrophoresis were observed. The altered conformation and/or organization of extraneural membrane proteins in Alzheimer's disease suggests the possibility that this disorder may have more widespread membrane involvement than was originally thought. PMID- 6245188 TI - Characterization of protein kinase system in human skeletal muscle. AB - The properties and distribution of basal and cyclic nucleotide stimulated protein kinases have been studied in normal and diseased human muscles. In particulate fraction of muscles from neurogenic atrophy the PK activity is remarkably lower than in control tissues, whereas in the cytosol of the same tissues an increase of enzyme activity was observed. In Duchenne dystrophy the PK activities were slighly lower than in controls both in particulate and in soluble fractions. The authors suggest that the altered subcellular distribution found in neurogenic atrophy might be due to the loss of nerve trophic control. PMID- 6245189 TI - Early phase of vincristine neuropathy in man. Electrophysiological evidence for a dying-back phenomenon, with transitory enhancement of spinal transmission of the monosynaptic reflex. AB - Ten patients with Hodgkin's disease were examined before and after each administration of vincristine sulfate (2 intravenous injections of 1.4 mg/m2 of body surface during the first week of each month for 3 months). The motor conduction velocity of the peroneal nerve, the conduction velocity in palmar sensory fibres of the median nerve, and the conduction velocity in the H reflex pathway remained unchanged. The amplitude of distal muscle (extensor digitorum brevis) and sensory nerve (median) potentials decreased, while the maximal response of more proximal muscles (soleus) was not significantly modified. The soleus T response quickly decreased, although at the same time the H response was increased in the days following administration of vincristine. Thus the T/H ratio seems to be the only convenient electrophysiological method of evaluating the functional impairment of primary afferent distal segments. These results show that vincristine induces a transitory excitability enhancement of the monosynaptic reflex. It is suggested that the drug may cause an increase in the firing rate in proximal segments of injured Ia fibres. Apart from this phenomenon the electrophysiological results lead to the conclusion that vincristine induces distal axonal degeneration, similar to that in other toxic neuropathies (e.g. acrylamide or n-hexane) where a dying-back process has been clearly demonstrated. PMID- 6245190 TI - Peripheral nerve involvement in pernicious anaemia. AB - Impairment of nervous function and thiamine metabolism were studied in 40 patients suffering from pernicious anaemia, 20 of whom had not been treated and the other 20 were on hydroxocobalamin therapy. Of the untreated patients 13 (65%) showed signs of peripheral nerve dysfunction with reduced conduction velocities, as compared with only 1 (5%) of the treated patients. Reduced blood thiamine levels were found in 16 of the untreated patients (80%), 10 (60%) of whom showed biochemical signs of thiamine deficiency. In the treated group, 7 patients (30%) had reduced blood thiamine levels. Thus, peripheral nerve involvement in pernicious anaemia is much more frequent than would be expected from the literature, and thiamine deficiency was present in the majority of these cases. PMID- 6245191 TI - The effects of spinal cord trauma on myelin. AB - Experimental spinal cord trauma was produced in rats by dropping a 10-g weight from a height of 30 cm upon exposed spinal cord. The histological lesion consisted of edema, necrosis, and hemorrhage. The fine structure of the early traumatic lesion (4 to 12 hours) included granular dissolution of axons and a characteristic vesiculation of myelin. The predominant ultrastructural features of older lesions (12 to 72 hours) were intra-axonal calcification and lipid-laden macrophages. The yield of myelin and the activity of adenosine 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) were reduced by approximately 15% at 4 hours and by 60% at 72 hours. Losses in all myelin proteins were observed, but were most severe and occurred earliest in the basic proteins. The ultrastructural and biochemical alterations observed in this study indicate that proteinase activity is increased and may be partially responsible for the traumatic myelinolysis in experimental spinal cord trauma. PMID- 6245192 TI - Primary intracerebral tumor with mixed chondrosarcoma and glioblastoma- gliosarcoma or sarcoglioma? AB - An unusual primary intracerebral tumor with combined features of chondrosarcoma and glioblastoma multiforme is presented. Glial elements showing a spectrum of hyperplastic and neoplastic changes were intermingled with sarcomatous areas, similar to that recently described by Lalitha and Rubinstein as "sarcoglioma." Many vessels in the gliomatous regions contained proliferating endothelial cells with marked cytologic abnormalities. Although no direct extension out of the vessel wall was conclusively identified, the possibility of sarcomatous change could not be completely excluded. We conclude that, in this case, we could not establish whether the sarcoma was primary and the glioma secondary ("sarcoglioma") or vice versa ("gliosarcoma"), nor could we rule out that the two components originated from the same ancestral pluripotential cells. PMID- 6245193 TI - Comparison of Tc-99m pyrosphosphate and Tc-99m hydroxymethylene diphosphonate in acute myocardial infarction: concise communication. AB - A clinical comparison between a new bone seeking radiopharmaceutical, Tc-99m hydroxymethylene diphosphonate (TcHMDP) and the standard agent, Tc-99m pyrophosphate (TcPPi), was performed in 18 patients with acute myocardial infarction. Each patient was imaged initially with either TcHMDP or TcPPi, and imaged 24 hr later with the other tracer. All 18 patients had images positive for acute myocardial infarction with TcPPi, whereas 16 of 18 patients (89%) had positive studies with TcHMDP. The TcPPi images were graded significantly superior to those obtained with TcHMDP in 61% of the patients, and they were equal in 33%. In only one patient (6%) was TcHMDP better. The results indicate that compared with TcHMDP, TcPPi not only has a superior sensitivity for acute myocardial infarction but also has a significantly increased intensity of uptake in positive areas. TcPPi remains the agent of choice for myocardial infarct imaging. PMID- 6245194 TI - An evaluation of prepackaged columns for the separation of carcinoembryonic antigen from perchloric acid: concise communication. AB - Commerically available Sephadex buffer-exchange columns for the separation of carcinoembryonic antigen (CEA) from perchloric acid were evaluated. Elution patterns of individual columns were found to be variable, but separation of acid from CEA could be accomplished. Repeatability of replicate elutions and agreement with dialysis results were acceptable. Nevertheless, the method is excessively time-consuming and inefficient for processing large numbers of patient samples. PMID- 6245195 TI - Effect of feeding cassava root meal on reproduction and growth of rabbits. AB - In an experiment designed to determine the effect of feeding cassava-based diets on reproduction of young rabbit does, 16 New Zealand White does, about 36 weeks old, were fed four diets containing 0, 15, 30 or 45% cassava root meal (CRM) daily plus 200 g of green herbage every other day. After being fed those diets for 42 days, the does were bred to bucks fed standard commercial diet. The does were bred two more times after the pups were weaned at 5 weeks of age. Offspring of the first breeding study were used in an 8-week growth trial by feeding them the same cassava-based diets as their dams. The number of pups per litter at birth, 14, 28 and 35 days postpartum and the live weight of pups at the same ages did not differ significantly between treatments. Similarly, the thiocyanate content of the urine and blood serum of the dams was similar for all treatments. Results of the growth study using the offspring of the first breeding showed the average rate of gain, feed consumption, efficiency of feed utilization, the fresh weight of skin, kidney, liver, heart, pancreas and visceral fat were not significantly different. Also the urine and serum thiocyanate concentrations were not different. PMID- 6245196 TI - Influence of adult age on the skeletal response to phosphate and estrogen in rats. AB - Sixteen-month-old ("aged") female rats were less susceptible than 6-month-old ("mature") females to parathyroid hormone (PTH)-mediated bone resorption induced by excess dietary phosphate. Ovariectomy enhanced 45Ca loss from the bones of mature rats but not of aged rats. In mature ovariectomized (OX) females, estradiol initially suppressed phosphate-induced bone resorption but its effectiveness decreased with continued administration. Diethylstilbestrol (DES) administered continuously or on a 3-weeks-on, 1-week-off schedule in the diet suppressed the increase in 45Ca loss in OX mature females fed a high (1.2%) P diet. In contrast, DES had no consistent effect on 45Ca loss by the aged animals. Urinary cyclic adenosine monophosphate (cAMP) was increased to a similar extent in both groups by feeding excess phosphate, indicating that the reduced effect of phosphate on 45Ca loss in the aged females was due to decreased bone response to PTH. Ovariectomies produced an increase in cAMP excretion which was suppressed by DES administration. DES also suppressed the increase in urinary cAMP induced by dietary phosphate, signifying that the decrease in bone resorption produced by estrogen is associated with an inhibition either of PTH synthesis or function. PMID- 6245197 TI - Technetium 99m pyrophosphate uptake in a case of unilateral condylar hyperplasia. PMID- 6245198 TI - The possible role of macrophages in transient hepatic fibrogenesis induced by acute carbon tetrachloride injury. PMID- 6245199 TI - Exocytosis by macrophage polykarya: an ultrastructural study. AB - Macrophage polykarya selectively secrete their lysosomal contents directly into the extracellular space or into the intracytoplasmic membranous labyrinth. Fusion of the lysosomal membrane with the plasmalemma or with the cytoplasmic labyrinth results in the release of the lysosomal contents. The labyrinth, however, was shown to be essentially similar to the plasmalemma, hinting that comparable mechanisms are involved in both instances. The process of secretion is unrelated to motility and phagocytosis and may be important in the extracellular degradation of biological material. PMID- 6245200 TI - Colon cancer after Wilms tumor. PMID- 6245201 TI - Fibrous histiocytoma. AB - A 13-year-old boy underwent excision of a fibrous histiocytoma, which was initially thought to be a leiomyoma. When the tumor recurred, it was resected using wide tissue margins and frozen section control. Visual acuity remained normal although there has been some postoperative diplopia. There has been no recurrence over the past year. A local aggressive surgical approach is advocated when this tumor appears in the pediatric age group. PMID- 6245202 TI - Experimental approach to the pathogenesis of the anomalies of amniotic disease. AB - By intra-adnexal injection of glucose in the rabbit embryo, we were able to stimulate all the anomalies associated with "Amniotic Disease". Since we were even able to obtain amniotic bands, this study provides an excellent experimental model of this disease. Resulting lesions occur early in development, corresponding to the first trimester of human gestation. All of the anomalies can ultimately be explained by the destruction of the most superficial cells: epiblastic cells of the embryo and the amnion, subjacent mesenchyme, and endothelial cells. The subsequent lack of interaction between these cells and the importance of the anatomical localizations of resulting hematomas can lead to the pathogenetic approach to this disease. In light of the present study, the disease appears to be caused by an external factor within the amniotic fluid. The exact nature of the destructive agent(s) remains a mystery in man. PMID- 6245203 TI - [Conjugated metabolites of morphine and the related compounds and their pharmacological activity (author's transl)]. PMID- 6245204 TI - [Studies on beta-lactam antibiotics. V. Synthesis of 6-[D(-)-alpha-(acylamino)-4 hydroxyphenylacetamido]penicillanic acids and antibacterial activity (author's transl)]. PMID- 6245205 TI - Effects of delta 9-tetrahydrocannabinol and cannabidiol on sodium-dependent high affinity choline uptake in the rat hippocampus. AB - Doses of delta 9-tetrahydrocannabinol (delta 9-THC) and cannabidiol (CBD) affording the same degree of protection against seizures induced by maximal electroshock were compared for their effects on sodium-dependent high affinity choline uptake into six rat brain regions: cortex, striatum, medulla-pons, hypothalamus, midbrain and hippocampus. One hour after administration of CBD, 60 mg/kg i.p. in vitro choline uptake was not altered in any brain region. In contrast, 1 hr after administration of delta 9-THC, 10 mg/kg i.p., in vitro choline uptake in hippocampus and hypothalamus was significantly reduced. Moreover, in vivo administration of delta 9-THC was followed by a dose-related reduction in in vitro hippocampus choline uptake. Kinetic analysis of hippocampal choline uptake after administration of delta 9-THC, 10 mg/kg i.p., indicated that there was a reduction in Vmax with no change in the Km of the transport system. After direct addition to the hippocampal homogenates (in vitro) both delta 9-THC and CBD inhibited choline uptake, with IC50 values of 4.6 and 15.9 microM, respectively. Kinetic analysis revealed that the in vitro choline uptake inhibition induced by delta 9-THC was noncompetitive in nature. These results suggest that the septal-hippocampal cholinergic tract is a major site of action of delta 9-THC and may provide a neurochemical basis for the differential pharmacological properties of delta 9-THC and CBD. PMID- 6245206 TI - Methadone-induced attenuation of the effects of delta 9-tetrahydrocannabinol on temporal discrimination in pigeons. AB - Pigeons responded under a discrete trial procedure in which they were required to peck one of two keys depending on the duration of a conditional stimulus (general illumination of the experimental chamber). Correct choices (red key after a 4-sec stimulus; green key after an 8-sec stimulus) resulted in the intermittent presentation of food; incorrect choices resulted in a darkened chamber. Intermediate durations (probe stimuli) were also presented occasionally. The effects of tetrahydrocannabinol (THC; 0.06-0.50 mg/kg) and repeated methadone injections (2-20 mg/kg/day) were assessed alone and in combination. THC resulted in a dose-dependent decrease in accuracy with the greater effect on long-duration trials. Repeated methadone alone resulted in a decrease in accuracy only when the methadone dose was changed. High doses of methadone (6 and 20 mg/kg/day) resulted in either a complete (0.25 mg/kg of THC) or partial (0.50 mg/kg of THC) attenuation of effects of THC on temporal discrimination accuracy as compared to a low methadone dose (2 mg/kg/day) or THC alone. The results suggest the possibility of cross-tolerance or antagonism between methadone and THC. PMID- 6245207 TI - delta 9-Tetrahydrocannabinol: a potent inhibitor of episodic luteinizing hormone secretion. AB - To determine if delta 9-tetrahydrocannabinol (THC) dosages comparable to those obtainable from marihuana cigarettes suppress episodic luteinizing hormone (LH) secretion, THC was administered to ovariectomized rats in doses of 31.2 to 500 microgram/kg b.wt. THC in doses of 62.5 microgram/kg b.wt. or greater rapidly suppressed episodic LH release and reduced serum LH concentrations by 42 to 68%. The period of suppression ranged from less than 30 min to more than 1 hr and was dose-dependent. These results indicate that acute exposure to relatively low doses of THC significantly disrupts gonadotropic hormone secretion in the rat and raise the question of whether episodic LH secretion in humans might be suppressed subsequent to the use of marihuana. PMID- 6245208 TI - Reactions in the foot pads of mice induced by pertussigen and endotoxin from Bordetella pertussis. PMID- 6245209 TI - Evidence that iodide transport into human polymorphonuclear leukocytes is not an active process. PMID- 6245210 TI - A novel opioid receptor site directed alkylating agent with irreversible narcotic antagonistic and reversible agonistic activities. PMID- 6245211 TI - Synthesis and enzymatic and inotropic activity of some new 8-substituted and 6,8 disubstituted derivatives of adenosine cyclic 3',5'-monophosphate. AB - The synthesis of certain new 8-(arythio)- and 8-(alkylthio)-cAMP derivatives and N6-alkyl- and N6-dialkyl-8-(arylthio) and -8-(alkylthio) derivatives of cAMP is reported. On the basis of activation of protein kinase, several N6-alkyl-8 (benzylthio)-cAMP derivatives were selected for evaluation as inotropic agents using cat papillary muscle in vitro. Activity in these studies resulted in the selection of several analogues for in vivo studies in the anesthetized dogs. The best inotropic agent selected on the basis of in vivo studies was N6-butyl-8 (benzylthio)-cAMP (26), which exhibited an increase in blood-flow rate of 85% with no increase in heart rate. A large-scale synthesis of 26 from cAMP is reported via N1-alkylation, followed by a Dimroth rearrangement, reduction, bromination, and nucleophilic displacement via benzyl mercaptan. The N6-alkyl-8 substituted-cAMP derivatives represent a new class of potent inotropic agents. The direct mechanism of action of 26 suggests the possible utility of this cyclic nucleotide to treat clinical myocardial infarction by rapid intravenous infusion. PMID- 6245213 TI - Synthesis, in vitro opiate activity, and intramolecular tyrosine--tryptophan distances of [4-tryptophan]enkephalin analogues. A reassessment of conformational models of enkephalin in solution. PMID- 6245212 TI - Synthesis of 5-[(methylthio)methyl]-2'-deoxyuridine, the corresponding sulfoxide and sulfone, and their 5'-phosphates: antiviral effects and thymidylate synthetase inhibition. AB - Substitution on the alpha position of thymidine with methylthio (3) and methylsulfonyl (5) groups gave antiviral agents that were specific and relatively nontoxic inhibitors of herpes simplex virus replication in cell culture. The thioether (3) was effective against both types 1 and 2 of herpes simplex virus, whereas the activity of the sulfone derivative (5) was restricted to herpes simplex virus type 1. The sulfoxide derivative 1-(2-deoxy-beta-D-ribofuranosyl) alpha-(methylsulfinyl)thymine (4) was inactive as an antiviral agent. The 5' phosphates of these three thymidine derivatives were relatively potent inhibitors of thymidylate synthetase (Ki values range from 7.8 to 1.9 microM). It is improbable that the inhibition of this enzyme accounts for the anti-herpes activity of compounds 3 and 5. PMID- 6245214 TI - Dermatoglyphic findings in Poland's syndrome. AB - The dermatoglyphs of four cases of Poland's syndrome were investigated and compared with those of previously reported cases. PMID- 6245215 TI - K+ influx components in ascites cells: the effects of agents interacting with the (Na+ + K+)-pump. AB - Several agents known to interact with the (Na+ + K+)-pump were tested for their effects on the components of steady-state K+ flux in ascites cells. 86Rb+ was used as a tracer for K+, and influx was differentiated into a ouabain-inhibitable "pump" component, a Cl--dependent and furosemide-sensitive "exchange" component, and a residual "leak" flux. All agents tested (ouabain, quercetin, oligomycin, phosphate) affected both the "pump" flux and the Cl--linked flux. These findings suggest a linkage between the activity of the Na/K ATPase and the Cl--dependent K+ exchange flux. In the discussion we point out that the mechanism of this linkage could be direct; e.g., Cl--dependent exchange may represent a mode of operation of the Na/K ATPase. However, data from this and other systems tend to suggest an indirect linkage between the Na+ pump and a KCl symporter, perhaps via a change in the level of intracellular ATP. PMID- 6245216 TI - Structural and functional membrane polarity in cultured monolayers of MDCK cells. AB - MDCK cells form monolayers which have many of the properties usually found in transporting epithelia. The present article is devoted to the study of the structural and functional polarization of MDCK cells, which is one of the central features of transporting epithelia. The results show: (i) that MDCK monolayers transport 2.6 mumol hr-1 cm-2 of sodium in the apical to basolateral direction; (ii) the passive flux of this ion is relatively large (20.3 mole hr-1 cm-2), which is a characteristic of leaky epithelia; (iii) a large fraction of the penetration of sodium into the cells proceeds through an amiloride-sensitive channel, and the exit is operated mainly by a ouabain-sensitive pump; (iv) the net transport of sodium from the apical to the basolateral side agrees with the asymmetric labeling of the pumps with 3H-ouabain; (v) this asymmetric labeling agrees, in turn, with a higher concentration of intramembrane particles (IMPs) in freeze-fracture replicas of the basolateral side of the plasma membrane; (vi) the structural polarization of confluent MDCK cells is also revealed by the location of microvilli, occluding junctions, and pinocytotic vesicles; and (vii) the presence of a continuous ring formed by actin microfilaments visualized by immunofluorescence under the lateral aspect of the plasma membrane that may be related to the distribution of the occluding junctions, which act as barriers separating apical from basolateral membrane components. PMID- 6245217 TI - Electron paramagnetic resonance and saturation transfer electron paramagnetic resonance studies on erythrocytes from goats with and without heritable myotonia. AB - Erythrocytes from myotonic goats, an animal model of heritable myotonia, and normal goats were studied using electron paramagnetic resonance (EPR) and saturation transfer electron paramagnetic resonance (ST-EPR) spin labeling techniques. Three fatty acid spin labels with the nitroxide moiety at progressively greater distances from the carboxyl group were used to monitor different regions within the erythrocyte membrane. Since spin labels have been shown to induce hemolytic and morphologic alterations in erythrocytes, conditions for minimizing these alterations were first defined by hemolysis studies and scanning electron microscopy. Using these defined conditions for our studies we observed no significant differences in any of the EPR or ST-EPR parameters for normal and myotonic goat erythrocytes with any of the fatty acid spin labels used. Our results do not support the theory that myotonia is the result of a generalized membrane defect characterized by increased membrane fluidity as determined by fatty acid spin labels. PMID- 6245218 TI - New evidence for the role of cyclic AMP in the release of mitochondrial calcium. PMID- 6245219 TI - Characterization of crystals of a cytochrome oxidase (nitrite reductase) from Pseudomonas aeruginosa by x-ray diffraction and electron microscopy. PMID- 6245220 TI - The mechanism of replication of phi x174 DNA. XVI. Evidence that the phi x174 viral strand is synthesized discontinuously. PMID- 6245221 TI - Maturation of newly replicated chromatin of simian virus 40 and its host cell. PMID- 6245222 TI - Kinetic study of protein unfolding and refolding using urea gradient electrophoresis. PMID- 6245223 TI - Inhibitory activity of blockers of the slow inward current in rat myocardium, a study in steady state and of rate of action. PMID- 6245224 TI - Herpesvirus-lymphoid cell interactions: comparative studies on the biology of herpes simplex virus-induced Fc receptors in B, T, and "null" lymphoid cell lines. AB - We have investigated the induction of Fc receptor (FcR) in different types of lymphoid cell lines (LCL) infected with herpes simplex virus (HSV). Subpopulations of certain of these LCL normally express FcR unrelated to herpetic infection. Differentiation of virus-induced FcR from that related to normal cell function was therefore possible. FcR detection was carried out by means of a rosette assay using ox erythrocytes coated with 7S immunoglobulin G (EA rosettes). Both HSV types 1 and 2 were found to induce FcR in B, T, and "null" (i.e., non-B, non-T) type LCL; however, in all the LCL tested, this HSV-induced FcR expression appeared to be more restricted in the responding T LCL than in responding B and null type LCL. In addition, kinetic experiments revealed that the time course of HSV-induced FcR expression differed among these LCL types tested. Interestingly, a number of LCL were resistant to HSV infection or restricted HSV gene expression, including expression of the viral products responsible for FcR induction. In all the responding HSV-infected LCL, induction of FcR always paralleled the expression of HSV antigens. Synthesis of HSV-induced FcR was shown to be inhibited by phosphonoacetic acid, an inhibitor of herpesvirus DNA polymerase activity, whereas FcR of non-HSV origin was found to be resistant to inhibitor. This would infer that HSV codes for an FcR which can be differentiated from that of cellular origin by using phosphonoacetic acid. Therefore, two different mechanisms of FcR synthesis may be suggested, one virus mediated and the second probably under cellular control. In addition, the data obtained using Epstein-Barr virus producer as well as isogeneic monoclonal cell lines, with and without the Epstein-Barr virus genome, indicated that the resident Epstein-Barr virus genome in the target cell did not have a detectable effect in the induction of FcR by HSV. PMID- 6245225 TI - Protein-protein interactions within paramyxoviruses identified by native disulfide bonding or reversible chemical cross-linking. AB - Analysis of native disulfide-bonded protein oligomers in paramyxoviruses showed that some viral proteins are consistently present as covalent complexes. In isolated Sendai virus the hemagglutinating protein HN is present in homodimeric and homotetrameric forms, and the minor nucleocapsid protein P exists partly as a monomer and partly as a disulfide-linked homotrimer. Similar disulfide-linked complexes were observed in Newcastle disease virus (strain HP-16), in which HN exists as a homodimer and some of the major nucleocapsid protein NP exists as a homotrimer. Noncovalent intermolecular interactions between proteins were studied with the reversible chemical cross-linkers dimethyl-3,3'-dithiobispropionimidate and methyl 3-[(p-azidophenyl)dithio]propionimidate, which contain disulfide bridges and a 1.1-nm separation between their functional groups. The same results were achieved with both reagents. The conditions of preparation, isolation, and storage of the viruses affected the protein-protein interactions observed upon cross-linking. Homooligomers of the glycoprotein F, the matrix protein M, and the major nucleocapsid protein NP were produced in both Sendai and Newcastle disease viruses after mild cross-linking of all viral preparations examined, but NP-M heterodimer formation in both viruses was most prevalent in early harvest preparations that were cross-linked soon after isolation. The ability of NP and M to form a heterodimer upon cross-linking indicates that the matrix protein layer lies in close proximity (within 1.1 nm) to the nucleocapsid in the newly formed virion. Some noncovalent intermolecular protein interactions in Sendai and Newcastle disease viruses, i.e., those leading to the formation of F, NP, and M homooliogmers upon cross-linking, are more stable to virus storage than others, i.e., those leading to the formation of an NP-M heterodimer upon cross-linking. The storage-induced loss of the ability of NP and M to form a heterodimer is not accompanied by any apparent loss of infectivity. This indicates that some spacial relationships which form during virus assembly can alter after particle formation and are not essential for the ensuing stages of the infectious process. PMID- 6245226 TI - Herpes simplex virus phosphoproteins. I. Phosphate cycles on and off some viral polypeptides and can alter their affinity for DNA. AB - We report on phosphorylation, the stability of the bound phosphate, and the properties of several phosphorylated infected-cell polypeptides (ICPs) synthesized in cells infected with herpes simplex virus 1 and 2. Our results and conclusions are as follows. (i) Phosphorylation of ICPs occurs by at least two different pathways. Thus, the 4a and 4c electrophoretic forms of ICP 4 were labeled with 32P during a pulse concurrently with their synthesis, whereas ICP 22 and ICP 27 were labeled with 32P only during a subsequent chase in the presence of unlabeled phosphate. (ii) Pulse chase studies with [35S]methionine and 32P indicate that whereas most polypeptides are stable, the bound phosphate with few exceptions cycles on and off. Of special interest is the observation that the phosphate bound to ICP 4a and 4c cycles on and off, whereas that bound to ICP 4b is stably associated. Similar cycling was observed for ICP 6, 11, 22, and 27. The observation that 4a and 4c can be phosphorylated as late as 24 h after infection, i.e., long after their synthesis ceases, suggests that all three forms may have defined functions that persist throughout the reproductive cycle. (iii) All three forms of ICP 4 can be the translational products of only one of two copies of the ICP 4 gene in the viral genome. (iv) Analyses of the distribution of the viral proteins within the cell indicate that phosphorylation is not a major determinant in the compartmentalization of most viral phosphoproteins. (v) Comparisons of the binding to DNA-cellulose of artificial mixtures of 32P- and [35S]methionine-labeled proteins from infected cells indicate that phosphorylation in some instances enhances (e.g., ICP 29) and in other instances decreases (e.g., ICP 6) binding affinity for DNA. In light of previous reports that some of the proteins identified as phosphoproteins have regulatory functions, the data suggest that phosphorylation may modify the activity of regulatory proteins in herpes simplex virus-infected cells. PMID- 6245227 TI - Effect of Fv-1 gene product on synthesis of linear and supercoiled viral DNA in cells infected with murine leukemia virus. AB - Levels of unintegrated viral DNA made in Fv-1b/b (SIM.R, JLS-V9) and Fv-1n/n (NIH/3T3) cell lines after infection with N- or B-tropic murine leukemia virus (MuLV) have been measured. Different forms of viral DNA were sedimented on neutral sucrose or ethidium bromide-cesium chloride density gradients and detected by hybridization with complementary DNA. It was found that the major viral DNA species made in Fv-1 permissive or resistant cells was sedimenting at 20S on neutral sucrose gradient. Levels of this 20S viral DNA species were not significantly different in both systems. However levels of closed circular (form I) viral DNA separated on ethidium bromide-cesium chloride gradients were found to be decreased in Fv-1 resistant cells. Various species of viral DNA were also analyzed by the agarose gel-DNA transfer procedure of Southern. The major viral DNA species was found to migrate as a double-stranded linear DNA of 5.7 x 10(6) daltons. The molecular weight of linear viral DNA molecules extracted from Fv-1 permissive or resistant cells appeared to be the same. Levels of this linear viral DNA were almost identical in both systems except in B-tropic MuLV-infected resistant NIH/3T3 cells in which a moderate decrease has been measured. Two closed circular viral DNA species were observed by this technique. Their levels were markedly decreased in Fv-1 resistant cells. Our results indicate that the Fv 1 restriction does not grossly affect the formation of linear double-stranded viral DNA, but prevents the accumulation of closed circular viral DNA. Therefore the Fv-1 gene product could allow the synthesis of a normal linear viral DNA but interfere with the formation of supercoiled viral DNA. Alternatively, it could promote the synthesis of a faulty linear viral DNA whose defect (yet undetected) would prevent its circularization. In any case, the Fv-1 restriction mechanism appears to occur before the integration event itself. PMID- 6245228 TI - Temperature-sensitive transformation by Rous sarcoma virus and temperature sensitive protein kinase activity. AB - The transforming protein of Rous sarcoma virus, p60src, has associated with it a protein kinase activity. We examined whether a correlation exists between the cellular concentration of enzymatically active p60src and the degree to which chick cells are transformed by mutants of Rous sarcoma virus which are temperature-sensitive for transformation. Such a correlation does exist, but cells infected with some mutants could be shown to contain, at the nonpermissive temperature, an amount of protein kinase activity equal to 30 to 40% of that in a wild-type transformed cell. We quantified the amount of virus-induced protein kinase activity by precipitation of p60src with an excess of antitumor antiserum. Our initial measurements of activity were serious underestimates, due to the lability of the protein kinase activity associated with p60src of at least four temperature-sensitive mutants. In fact, no activity at all was associated with p60src of tsLA90 when immunoprecipitation was performed by standard means. However, when immunoprecipitation was performed with procedures which minimize inactivation, it became apparent both that cells transformed by tsLA90 contained protein kinase activity and that cells infected with either NY68 or BK5 contained at the nonpermissive temperature, one-third to one-half as much activity as wild type transformed cells. This level of activity was much more than that arising from p60sarc in uninfected cells. In uninfected cells we found an amount of protein kinase activity which varied from 3 to 5% as much as that in a virally transformed cell. The lability of the protein kinase activity of each of these mutants is a further demonstration that this activity is essential for the transformation of cells by Rous sarcoma virus. So as to explain the high protein kinase levels in cells infected with NY68 and BK5 at the nonpermissive temperature, the idea that transformation may be a response to a small quantitative change in the total activity of p60src and the possibility that there may be more than one viral function which is essential for transformation are discussed. PMID- 6245229 TI - Recombinants between endogenous and exogenous avian tumor viruses: role of the C region and other portions of the genome in the control of replication and transformation. AB - Endogenous retroviruses of chickens are closely related to exogenous viruses isolated from spontaneous tumors in the same species, yet differ in a number of important characteristics, including the ability to transform cells in culture, ability to cause sarcomas or leukemias, host range, and growth rate in cell culture. To correlate these differences with specific sequence differences between the two viral genomes, the genome RNA of transforming subgroup E recombinants between the Prague strain of Rous sarcoma virus, subgroup B (Pr-RSV B), and the endogenous Rous-associated virus-0 (RAV-0), Subgroup E, and seven nontransforming subgroup E recombinants between the transformation-defective mutant of Pr-RSV-B and RAV-0 was examined by oligonucleotide fingerprinting. The pattern of inheritance among the recombinant viruses of regions of the genome in which Pr-RSV-B and RAV-0 differ allowed us to draw the following conclusions. (i) Nonselected parts of the genome were, with a few exceptions, inherited by the recombinant virus progeny randomly from either parent, with no obvious linkage between neighboring sequences. (ii) A small region in the Pr-RSV-B genome which maps in the 5' region was found in all transforming but only some of the nontransforming recombinants, suggesting that it plays a role in the control of the expression of transformation. (iii) A region of the Pr-RSV-B genome which maps between env and src was similarly linked to the src gene and may be either part of the structural gene for src or a control sequence regulating the expression of src. (iv) The C region at the extreme 3' end of the virus genome which is closely related in all the exogenous avian retroviruses but distinctly different in the endogenous viruses is the major determinant responsible for the differences in growth rate between RAV-0 and Pr-RSV-B. This latter observation allowed us to redefine the C region as a genetic locus, c, with two alleles cn (in RAV-0) and cx (in exogenous viruses). PMID- 6245230 TI - Ev 2, a genetic locus containing structural genes for endogenous virus, codes for Rous-associated virus type 0 produced by line 72 chickens. AB - ev 2 is one of seven recently described genetic loci of chickens which contain structural genes for endogenous virus. ev 2 is present exclusively in line 72 chickens, an inbred strain of white Leghorns which is homozygous for the capacity to produce Rous-associated virus type 0 (RAV-0), a subgroup E virus. This phenotype is known as V+ and has been assigned a genetic allele designated V-E7. The segregation of ev 2 was followed in a genetic cross in which the V-E7+ phenotype was also segregating. The progeny of the cross were analyzed for endogenous viral loci by cleavage of embryo DNA with restriction endonuclease SstI, electrophoretic separation of the resulting fragments, and identification of bands containing viral sequences by hybridization of the DNA to radiolabeled viral RNA. Four endogenous viral loci, ev 1, ev 2, ev 4, and ev 5, were identified in the progeny of the cross. One of the progeny contained no detectable endogenous viral sequences. ev 1, ev 4, and ev 5 were present in progeny of both the V-E7+ and V-E7- phenotypes. ev 2 was present exclusively in progeny of the V-E7+ phenotype, and all V-E7+ progeny contained ev 2. In addition, one of the V-E7+ progeny contained only ev 2. FRom these data, we conclude that ev 2 codes for RAV-0 virus produced by the cells of line 72 chickens. PMID- 6245231 TI - Changes in three of the four coat proteins of oral polio vaccine strain derived from type 1 poliovirus. AB - Little is yet known about the nature, or extent, of the changes involved in attenuation of neurovirulent poliovirus. The tryptic comparison reported here, of coat proteins from the Sabin type 1 polio vaccine and parental Mahoney virus, provides a useful approach and affords some insight into this question. The main obstacle, separation of the labile proteins VP1 and VP2 in an intact state from the vaccine strain, was overcome by incorporating 3.5 M urea into an otherwise standard preparative gel electrophoresis system. Tryptic maps revealed six altered leucine-containing peaks: two in VP1, none in VP2, three in VP3, and one in VP4. It is estimated, after correcting for leucine-free peptides, that the coat protein sequences may have undergone some 10 to 13 amino acid replacements, roughly 1.5% of the total, in the course of attenuation leading to the vaccine strain. PMID- 6245232 TI - Identification of the herpes simplex virus DNA sequences present in six herpes simplex virus thymidine kinase-transformed mouse cell lines. AB - We have used a novel filter hybridization approach to detect and map the herpes simplex virus (HSV) DNA sequences which are present in four HSV thymidine kinase (HSVtk+)-transformed cell lines which were derived by exposure of thymidine kinase negative (tk-) mouse cells to UV light-irradiated HSV type 2 (HSV-2). In addition, we have mapped the HSV-1 DNA sequences which are present in two HSV 1tk+-transformed cell lines produced by transfection of tk- mouse cells with sheared HSV-1 DNA. The results of these studies can be summarized as follows. (i) The only HSV DNA sequences which were common to all HSVtk+-transformed cells were those located between map coordinates 0.28 and 0.32. Thus, this region contains all of the viral DNA sequences which are necessary for the expression of HSV mediated tk transformation. (ii) Many of the cell lines also contained variable amounts of non-tk gene viral DNA sequences located between map coordinates 0.11 to 0.57 and 0.82 to 1.00, suggesting that incorporation of the viral DNA sequences located between these map coordinates is a relatively random event. (iii) The viral DNA sequences located between map coordinates 0 to 0.11 and 0.57 to 0.82 were uniformly absent from all of the HSVtk+ cell lines tested, suggesting that there is a strong negative selective pressure against incorporation of these viral DNA sequences. PMID- 6245233 TI - Order of polyadenylic acid addition and splicing events in early adenovirus mRNA formation. AB - A study of the processing of mRNA from two early adenovirus type 2 transcription units (regions 2 and 4 of adenovirus type 2 genome; [J. Flint, Cell 10:153--166, 1977]) revealed that polyadenylic acid [poly(A)] was added in most if not all cases to an unspliced nuclear RNA molecule whose coordinates extended from the apparent initiation site for RNA synthesis to the single poly(A) site in each transcription unit. An intermediate RNA molecule in the processing of the mRNA for the 72,000-M, single-stranded DNA binding protein showed that the first of the two intervening sequences, the one closest to the 5' end of the molecule, was removed first at least in the majority of the processed molecules. Finally, in cells labeled for 10 min and then treated with actinomycin D to stop further RNA synthesis, the majority, if not all, of the poly(A)-terminated nuclear RNA specific for region 2 was successfully processed and transported to the cytoplasm. PMID- 6245234 TI - Nature of the Sendai virus receptor: glycoprotein versus ganglioside. AB - Gangliosides were compared with glycoproteins as potential receptors for Sendai virus by incorporating measured amounts of the glycoconjugates into lecithin cholesterol liposomes and measuring binding by a hemagglutination assay with sheep erythrocytes. HeLa cell gangliosides showed no binding activity toward the virus up to 15 micrograms of sialic acid per 5 mumol of lecithin-cholesterol, whereas HeLa cell glycoproteins incorporated into similar liposomes caused avid virus binding below 1 microgram of sialic acid. These sialoglycoproteins could be separated from the bulk of cell proteins by multiple chloroform-methanol extractions. Purified rat brain gangliosides at a level of 120 micrograms of sialic acid in liposomes did not bind virus, whereas chloroform-methanol extracted rat brain proteins caused only marginal binding. Bovine brain gangliosides differed slightly from the rat brain mixture in showing weak binding properties. Our results thus indicate that glycoproteins, rather than gangliosides, are the natural receptors for Sendai virus and that tissues differ as to the quantity of such protein receptors. PMID- 6245235 TI - Analysis of the nucleic acid components in reticuloendotheliosis virus. AB - Reticuloendotheliosis virus (REV) is known to be capable of transforming chicken bone marrow cells in vivo and embryo fibroblasts in vitro. As with spleen necrosis virus, we have found that sequences related to REV are found in DNA of several uninfected avian species. For example, about 15% of the [3H]cDNA synthesized in the endogenous reverse transcriptase reaction reassociated with DNA of uninfected chickens. Kinetic analysis revealed only a few (less than five) such sequences per haploid genome, and the thermal stability of the reassociated duplex indicated less than perfect complementarity. Comparison of REV propagated in an avian cell line with REV grown in a canine line has revealed clear differences between the two isolates. Viral RNA and [3H]cDNA of REV isolated from the transformed chicken bone marrow cell line appear to consist of at least three sequence classes. The most numerous of these classes is highly related to REV propagated in canine cells. Only slightly less abundant is a class unrelated to RNA isolated from the canine virus but highly related to sequences found in normal uninfected avian cellular DNA. A third component is present at about 1% the level of the most numerous class. Although REV appears to be unrelated to the other known avian retroviruses, distant relatedness between p30's of REV and various mammalian type C viruses has recently been reported. We have asked whether REV-related sequences can be detected in various mammalian DNAs and viral RNAs. Hybridization experiments performed at low stringency have revealed no such sequences. PMID- 6245236 TI - In vitro recombination of bacteriophage T7 DNA damaged by UV radiation. AB - A system capable of in vitro packaging of exogenous bacteriophage T7 DNA has been used to monitor the biological activity of DNA replicated in vitro. This system has been used to follow the effects of UV radiation on in vitro replication and recombination. During the in vitro replication process, a considerable exchange of genetic information occurs between T7 DNA molecules present in the reaction mixture. This in vitro recombination is reflected in the genotype of the T7 phage produced after in vitro encapsulation; depending on the genetic markers selected, recombinants can comprise nearly 20% of the total phage production. When UV irradiated DNA is incubated in this system, the amount of in vitro synthesis is reduced and the total amount of viable phage produced after in vitro packaging is diminished. In vitro recombination rates are also lower when the participating DNA molecules have been exposed to UV. However, biochemical and genetic measurements confirmed that there is little or no transfer of pyrimidine dimers from irradiated DNA into undamaged molecules. PMID- 6245237 TI - Abelson murine leukemia virus mutants with alterations in the virus-specific P120 molecule. AB - Abelson murine leukemia virus (A-MuLV) is a replication-defective virus that transforms both fibroblasts and hematopoietic cells in vitro. The virus encodes a 120,000-molecular-weight protein (P120) that is composed of Moloney murine leukemia virus-derived gag gene sequences and A-MuLV--specific sequences. This protein is the only A-MuLV--encoded protein that has been detected, and thus P120 is a candidate for the transforming protein of A-MuLV. We now report isolation and characterization of three new A-MuLV isolates that do not synthesize P120 but do produce analogous proteins of larger (160,000 molecular weight) and smaller (100,000 and 90,000 molecular weight) size. All of these A-MuLV isolates transform fibroblasts and lymphoid cells in vitro. Because the different A-MuLV proteins vary in the A-MuLV--specific region of the molecule, these variants may set a maximum limit on the size of the A-MuLV transforming protein. PMID- 6245238 TI - Analysis of the genome of an endogenous, ecotropic retrovirus of the AKR strain of mice: micromethod for detailed characterization of high-molecular-weight RNA. AB - A detailed characterization of the genome of an endogenous, ecotropic type C virus, the Akv virus, is presented. Approximately 100 RNase T1-resistant oligonucleotides characteristic of the Akv genome were identified by two dimensional gel electrophoresis, and the complete nucleotide sequence is presented for 75 of these oligonucleotides. A correspondence between the sequence of some of these oligonucleotides and the amino acid sequence of some virus-coded gag gene proteins is reported. For this study we developed methods suitable for the analysis of high-molecular-weight RNA species in nanogram quantities. The in vitro labeling procedures used here led to uniform labeling of the unique oligonucleotides. PMID- 6245239 TI - Structure of murine sarcoma virus DNA replicative intermediates synthesized in vitro. AB - Moloney murine sarcoma virions synthesize discrete DNA products in vitro which closely resemble those found in vivo shortly after infection. These in vitro products have been isolated by electrophoresis and mapped with restriction endonucleases. In addition to the full-genome-length 6-kilobase pair linear DNA, a 5.4-kilobase pair circular DNA molecule, an incomplete linear DNA molecule, and a 600-base pair molecule were detected. The 6-kilobase pair DNA contained a 600 base pair direct terminal repeat which was missing from the circular form and was partially represented on the incomplete linear DNA molecule. The 600-base pair DNA contained sequences which were present in the 600-base pair direct repeat on the 6-kilobase pair DNA. The order of synthesis and the structure of these molecules detected in the in vitro reaction suggest that they are crucial intermediates in the formation of the final product of in vitro reverse transcription. A model which accounts for the synthesis of all of these molecules during the initial stages of viral replication is suggested. PMID- 6245240 TI - New map of bacteriophage lambda DNA. AB - A map of bacteriophage lambda was constructed, including accurate positions for all 41 cut sites made by 12 different restriction enzymes. Over 100 fragments from single, multiple, and partial enzyme digestions were measured versus standards that were calibrated with respect to DNA molecules of known sequence. The data were subjected to least-squares analysis to assign map coordinates. In no case did a fragment size predicted from the map differ from the measurement of the fragment by more than +/- 5%. This low error rate was consistent in all size ranges of fragments. The total length of lambda was calculated as 49,133 nucleotide pairs. This probably is accurate to within 500 base pairs. PMID- 6245241 TI - Restriction maps for twenty-one Charon vector phages. AB - The mapping of the sites of cleavage of nine restriction endonucleases (EcoRI, HindIII, BamHI, SalI, KpnI, SstI, BglII, XhoI, and XbaI) on 21 Charon phage vectors is described. Maps of individual subsections were obtained and then combined to assemble the complete vector maps. Calculations of maximum and minimum sizes of inserts which may be carried by the vectors using different restriction endonucleases or pairs of restriction endonucleases are presented. The regions mapped include several parts of phi 80 that had not been mapped previously. PMID- 6245242 TI - Vesicular stomatitis virus growth in Drosophila melanogaster cells: G protein deficiency. AB - In cultured Drosophila melanogaster cells, vesicular stomatitis virus (VSV) established a persistent, noncytopathic infection. No inhibition of host protein synthesis occurred even though all cells were initially infected. No defective interfering particles were detected, which would explain the establishment of the carrier state. In studies of the time course of viral protein synthesis in Drosophila cells, N, NS, and M viral polypeptides were readily detected within 1 h of infection. The yield of G protein and one of its precursors; G1, was very low at any time of the virus cycle; the released viruses always contained four to five times less G than those produced by chicken embryo cells, whatever the VSV strain or serotype used for infection and whatever the Drosophila cell line used as host. Actinomycin D added to the cells before infection enhanced VSV growth up to eight times. G and G1 synthesis increased much more than that of the other viral proteins when the cells were pretreated with the drug; nevertheless, the released viruses exhibited the same deficiency in G protein as the VSV released from untreated cells. Host cell control on both G-protein maturation process and synthesis at traduction level is discussed in relation to G biological properties. PMID- 6245243 TI - Isolation of coronavirus envelope glycoproteins and interaction with the viral nucleocapsid. AB - The two envelope glycoproteins and the viral nucleocapsid of the coronavirus A59 were isolated by solubilization of the viral membrane with Nonidet P-40 at 4 degrees C followed by sucrose density gradient sedimentation. Isolated E2 consisted of rosettes of peplomers, whereas E1, the membrane glycoprotein, was irregular and amorphous. Under certain conditions significant interactions occurred between components of Nonidet P-40-disrupted virions. Incubation of the Nonidet P-40-disrupted virus at 37 degrees C resulted in formation of a complex between one of the viral glycoproteins, E1, and the viral nucleocapsid. This was caused by a temperature-dependent conformational change in E1, resulting in aggregation of E1 and interaction with the viral RNA in the nucleocapsid. E1 also bound rRNA. The E1-nucleocapsid complexes can be distinguished on sucrose and Renografin density gradients from native viral nucleocapsids. The separation of the membrane glycoprotein E1 from the peplomeric glycoprotein E2 permitted preparation of antisera against these isolated proteins. A model is proposed for the arrangement of the three major structural proteins in the coronavirus A59 virion in relation to the viral envelope and RNA. PMID- 6245244 TI - Transfection of molecularly cloned Friend murine leukemia virus DNA yields a highly leukemogenic helper-independent type C virus. AB - Unintegrated viral DNA was isolated via the Hirt procedure from mouse fibroblasts newly infected with Friend murine leukemia virus (F-MuLV) clone 201, a biologically cloned helper virus isolated from stocks of F-MuLV complex. A physical map of the unintegrated in vivo linear viral DNA was generated for several restriction endonucleases. The supercoiled viral DNA was digested with EcoRI, which cleaved the viral DNA at a unique site. The linearized viral DNA was then inserted into lambda gtWES.lambda B at the EcoRI site and cloned in an approved EK2 host. Eight independent lambda-mouse recombinants were identified as containing F-MuLV DNA inserts by hybridization with F-MuLV 32P-labeled complementary DNA. One of the F-MuLV DNA inserts was 9.1 kilobases (kb) and had the same restriction enzyme sites as the unintegrated linear F-MuLV DNA. Six inserts were 8.5 kb; each lacked a single copy of the terminally redundant sequences of the unintegrated linear viral DNA. One insert was 8.2 kb and contained a 0.9-kb deletion. After digestion with EcoRI, one recombinant DNA preparation containing an 8.5-kb insert was infectious for NIH 3T3 cells. Undigested recombinant DNA was not infectious. The infectivity of the EcoRI digested DNA followed multihit kinetics, indicating that more than one molecule was required to register as an infectious unit. The virus isolated from this transfection (F-MuLV-57) was NB-ecotropic, helper-independent, and formed XC plaques. Inoculation of this virus into newborn NIH Swiss mice induced leukemia and splenomegaly in greater than 90% of animals within 3 to 4 weeks. The gross and microscopic abnormalities induced by F-MuLV clone 57 were identical to those seen with the original parent stocks of F-MuLV clone 201. These results indicate that this helper-independent F-MuLV can induce a rapid nonthymic leukemia in the absence of the spleen focus-forming virus. PMID- 6245245 TI - Genome organization of retroviruses. V. In vitro-synthesized Moloney murine leukemia viral DNA has long terminal redundancy. AB - Purified virions of Moloney murine leukemia virus can synthesize genome-length double-stranded DNA in vitro. Two predominant species of long DNA transcripts, with average sizes of 9.1 and 8.5 kilobases (kb) can be identified. Both species of DNA contain the negative (complementary to viral RNA) and positive (same polarity as viral RNA) strands. However, only the negative strand of the 8.5-kb species can be identified if the synthesis of DNA is carried out in the presence of the drug actinomycin D. The 9.1-kb species appears to be slightly larger than the genomic RNA. If the linear double-stranded 9.1-kb species is treated with Escherichia coli exonuclease III and allowed to anneal, circular DNA molecules can be observed. Furthermore, polyadenylate-containing short genomic RNA fragments (0.5 to 1.0 kb) can anneal to both the 5' and the 3' termini of 9.1-kb complementary DNA. The polyadenylate moiety of the RNA fragments can be identified by tagging it with circular polyoma DNA containing polydeoxybromouridylic acid tails. Thus, the 9.1-kb complementary DNA transcript with two circular polyoma DNA molecules at its termini can be observed. However, when similar annealings are performed with 8.5-kb complementary DNA species, only one end of the resulting molecule has circular polyoma DNA. We conclude that the 9.1-kb complementary DNA species has a large terminal redundancy. The sequences involved in terminal redundancy appear to be derived from the 3' end of the genomic RNA. PMID- 6245246 TI - Correlation between cell killing and massive second-round superinfection by members of some subgroups of avian leukosis virus. AB - Avian leukosis viruses of subgroups B, D, and F are cytopathic for chicken cells, whereas viruses of subgroups A, C, and E are not. The amounts of unintegrated linear viral DNA in cells at different times after infection with cytopathic or noncytopathic viruses were determined by hybridization and transfection assays. Shortly after infection, there is a transient accumulation of unintegrated linear viral DNA in cells infected with cytopathic avian leukosis viruses. By 10 days after infection, the majority of this unintegrated viral DNA is not present in the infected cells. The transient cytopathic effect seen in these infected cells also disappears by this time. Low amounts of unintegrated linear viral DNA persist in these cells. Cells infected with noncytopathic viruses do not show this transient accumulation of unintegrated viral DNA. Cells infected with cytopathic viruses and subsequently grown in the presence of neutralizing antibody do not show the transient accumulation of unintegrated viral DNA or cytopathic effects. These results demonstrate a correlation between envelope subgroup, transient accumulation of unintegrated linear viral DNA, and transient cell killing by avian leukosis viruses. The cell killing appears to be the result of massive second-round superinfection by the cytopathic avian leukosis viruses. PMID- 6245247 TI - Organization of repeated regions within the Epstein-Barr virus DNA molecule. AB - Virions of human Epstein-Barr virus released from the B95-8 line of marmoset lymphoblasts have linear double-stranded DNA molecules of 115 x 10(6) molecular weight (180 +/- 10 kilobase pairs). Approximately 20% of this DNA yields multiple fragments of 3,200 base pairs when cleaved with any one of the BglII, BamHI, PvuII, SacI, SstII, or XhoI restriction enzymes. The results of cleavage site mapping with these and other enzymes, together with blot hybridization experiments using the 3.2-kilobase pair BglII-R fragment as a probe, indicate that these fragments originate from an internal region between 0.710 and 0.915 map units containing a cluster of at least 12 apparently identical repetitions of a sequence with relatively high guanine plus cytosine content. The repeat units are arranged in adjacent tandem array with all copies having the same orientations, and they form a series of oligomers of tailed double-stranded circles when fragments containing portions of the cluster are denatured and reannealed. Physical maps of cleavage sites within the 3.2-kilobase pair repeat units and in the flanking sequences surrounding the repeat cluster have been constructed. We conclude that the Epstein-Barr virus DNA molecule, like those of other mammalian herpesviruses, may be regarded as being divisible into a large L segment and a smaller S segment. However, the detailed arrangement of repetitive sequences within the Epstein-Barr virus S segment differs significantly from that in all other herpesvirus genomes described so far. PMID- 6245248 TI - Heterogeneity of vesicular stomatitis virus particles: implications for virion assembly. AB - Vesicular stomatitis virus (VSV) particles formed at early times after infection contain only one-third the amount of viral glycoportein (G protein), relative to the major internal structural proteins M and N, as is found in particles released later. These "early" particles also have a lower density in equilibrium sucrose gradients than do those formed later; however, the sedimentation velocity and specific infectivity of these two classes of particles are the same. VSV-infected cells also release virus-like particles which sediment considerably faster than authentic virions and contain a higher-than-normal proportion of the VSV G protein relative to internal VSV proteins. These particles have a reduced specific infectivity but a normal density in sucrose gradients. All classes of VSV virions contain a constant proportion of M and N polypeptides. The ratio of G protein to M or N protein, in contrast, can vary over a sixfold range; this implies that an interaction between a precise number of surface G proteins with either of the underlying M and N proteins is not a prerequisite for budding of infectious viral particles from the cell surface. PMID- 6245249 TI - Reverse transcription of avian sarcoma virus RNA into DNA might involve copying of the tRNA primer. AB - Some of the double-stranded DNA products from the endogenous reaction of detergent-disrupted virions contain up to 18 3'-terminal nucleotides at a location consistent with their being transcribed from the tRNA primer. PMID- 6245250 TI - Early events after infection of Escherichia coli by bacteriophage T5. III. Inhibition of uracil-DNA glycosylase activity. AB - The activity of uracil-DNA glycosylase in Escherichia coli decreases dramatically to less than 10% of its original level after infection of the cells by phage T5. Phage-induced protein synthesis is required for this inhibition to occur, and the inhibition is induced by a mutant capable of injecting only the first 8% of its DNA. The inhibitor activity in extracts of infected cells is heat labile and nondialyzable, and will inhibit enzyme activity present in extracts of uninfected cells. PMID- 6245251 TI - ADP ribosylation of Escherichia coli RNA polymerase is nonessential for bacteriophage T4 development. AB - The bacteriophage T4-induced alt and mod gene products covalently add ADP-ribose to the Escherichia coli RNA polymerase alpha polypeptides; phage carrying either an alt or a mod mutation are viable. A genetic cross between T4alt and T4mod phages yielded alt mod recombinant progeny which could not ADP ribosylate RNA polymerase at all, yet grew apparently normally. Thus, ADP ribosylation of RNA polymerase appeared to be nonessential for T4 development (at least in E. coli B/r and E. coli CR63), even though the phage has evolved two distinct enzymes to catalyze this reaction. PMID- 6245252 TI - Transformation of BALB/c-3T3 cells by tsA mutants of simian virus 40: effect of transformation technique on the transformed phenotype. AB - Simian virus 40 tsA-transformed BALB/c-3T3 cells isolated as foci of overgrowth in liquid medium were compared with those isolated as colonies in soft agar. Efficiencies of transformation were equivalent in the two procedures. Cells isolated as foci were able to grow in agar and vice versa. No difference in temperature sensitivity of the transformed phenotype was detected when tsA transformants selected in agar were compared with those selected as foci. The use of the two different transformation procedures, then, did not form the basis for generation of different transformed phenotypes, and transformants generated in both ways were dependent upon expression of the A gene for maintenance of the transformed state. PMID- 6245253 TI - Characterization of RNA synthesized in isolated nuclei of herpes simplex virus type 1-infected KB cells. AB - Nuclei isolated from herpes simplex virus (HSV)-infected KB cells actively synthesize HSV RNA in vitro; the RNA can be hybridized with HSV DNA or nuclear RNA from HSV-infected cells. Nascent RNA molecules labeled in vivo with 32PO4 were elongated, utilizing the nuclear system to incorporate Hg-CTP at their 3' ends, and then isolated on an affinity column. Hybridization of isolated nascent RNA molecules showed that greater than 50% of them were HSV specific and that more than 25% were self-complementary. PMID- 6245254 TI - Location of the initiation site for protein synthesis on foot-and-mouth disease virus RNA by in vitro translation of defined fragments of the RNA. AB - An mRNA-dependent reticulocyte lysate has been used to translate foot-and-mouth disease virus RNA in vitro. Polypeptides P16, P20a, and P88, which have been shown to be derived from the 5' end of the RNA by pactamycin mapping experiments with infected cells, were preferentially synthesized in vitro. Removal of VPg, the small protein covalently linked to the 5' end of the genome RNA, had no effect on the translation of the RNA. The two RNA fragments (L and S) produced by specific digestion of the polycytidylic acid [poly(C)] tract with RNase H were also translated in vitro. The L fragment, consisting of RNA to the 3' side of the poly(C) tract and including the polyadenylic acid [poly(A)] tract, directed the synthesis of the same products as those made by full-length RNA. However, no small defined products were produced when the S fragment, which contains the 5' end of the RNA, was translated. These results show that the major initiation site for protein synthesis on foot-and-mouth disease virus RNA is to the 3' side of the poly(C) tract. Furthermore, the use of N-formyl [35S]methionine tRNAfMet as a label for the initiation peptides showed that the major polypeptide labeled in lysates primed with both full-length RNA and the L fragment was P16, i.e., the protein nearest the initiation site for translation as deduced from pactamycin mapping experiments. Fragments of RNA were also translated in vitro. Those containing the poly(C) tract gave products similar to those produced when full length RNA was translated. The polypeptides synthesized when fragments containing the poly(A) tract were used, however, did not resemble those made from full length RNA. PMID- 6245255 TI - Comparisons of nucleotide sequences in the genomes of the New Jersey and Indiana serotypes of vesicular stomatitis virus. AB - Nucleotide sequences of around 200 residues were determined adjacent to the 3' terminus of the genome RNA of vesicular stomatitis virus, New Jersey serotype, and adjacent to the 3'-terminal polyadenylic acid tract of the N protein mRNA of the same virus. These sequences were compared with the corresponding sequences previously determined for the Indiana serotype of vesicular stomatitis virus. The sequences obtained for the two strains were readily aligned, showing 70.8% homology overall. Examination of the sequences allowed identification of the translation initiation and termination codons for the N mRNA of each serotype. The deduced N-terminal and C-terminal amino acid sequences of the two N polypeptides were each similar, and most of the differences between them consisted of substitution by a clearly homologous amino acid. It was proposed that these nucleotide sequences, within limits imposed by their functions, comprise reasonably representative measures of the extent of sequence homology between the genomes of the two serotypes, and that this is higher than previously estimated, but with little exact homology over extended regions. PMID- 6245256 TI - Specific association of simian virus 40 tumor antigen with simian virus 40 chromatin. AB - Simian virus 40 tumor antigen (SV40 T antigen) was bound to both replicating and fully replicated SV40 chromatin extracted with a low-salt buffer from the nuclei of infected cells, and at least a part of the association was tight specific. T antigen cosedimented on sucrose gradients with SV40 chromatin, and T antigen chromatin complexes could be precipitated from the nuclear extract specifically with anti-T serum. From 10 to 20% of viral DNA labeled to steady state with [3H]thymidine for 12 h late in infection or 40 to 50% of replicating viral DNA pulse-labeled for 5 min was associated with T antigen in such immunoprecipitates. After reaction with antibody, most of the T antigen-chromatin complex was stable to washing with 0.5 M NaCl, but only about 20% of the DNA label remained in the precipitate after washing with 0.5 M NaCl-0.4% Sarkosyl. This tightly bound class of T antigen was associated preferentially with a subfraction of pulse-labeled replicating DNA which comigrated with an SV40 form I marker. A tight binding site for T antigen was identified tentatively by removing the histones with dextran sulfate and heparin from immunoprecipitated chromatin labeled with [32P]phosphate to steady state and then digesting the DNA with restriction endonucleases HinfI and HpaII. The site was within the fragment spanning the origin of replication, 0.641 to 0.725 on the SV40 map. PMID- 6245257 TI - Number and location of mouse mammary tumor virus proviral DNA in mouse DNA of normal tissue and of mammary tumors. AB - The Southern DNA filter transfer technique was used to characterize the genomic location of the mouse mammary tumor proviral DNA in different inbred strains of mice. Two of the strains (C3H and CBA) arose from a cross of a Bagg albino (BALB/c) mouse and a DBA mouse. The mouse mammary tumor virus-containing restriction enzyme DNA fragments of these strains had similar patterns, suggesting that the proviruses of these mice are in similar genomic locations. Conversely, the pattern arising from the DNA of the GR mouse, a strain genetically unrelated to the others, appeared different, suggesting that its mouse mammary tumor proviruses are located in different genomic sites. The structure of another gene, that coding for beta-globin, was also compared. The mice strains which we studied can be categorized into two classes, expressing either one or two beta-globin proteins. The macroenvironment of the beta-globin gene appeared similar among the mice strains belonging to one genetic class. Female mice of the C3H strain exogenously transmit mouse mammary tumor virus via the milk, and their offspring have a high incidence of mammary tumor occurrence. DNA isolated from individual mammary tumors taken from C3H mice or from BALB/c mice foster nursed on C3H mothers was analyzed by the DNA filter transfer technique. Additional mouse mammary tumor virus-containing fragments were found in the DNA isolated from each mammary tumor. These proviral sequences were integrated into different genomic sites in each tumor. PMID- 6245258 TI - Isolation and characterization of recombinant DNA clones of avian retroviruses: size heterogeneity and instability of the direct repeat. AB - Unintegrated proviral DNA of Schmidt-Ruppin B Rous sarcoma virus was cloned in the bacteriophage lambda vector Charon 21A. A total of 12 independent recombinant lambda SRBtd clones which were derived from the transformation-defective component in the viral preparation were analyzed with restriction endonucleases and molecular hybridization techniques. Three classes of clones were observed. Type I clones contained a 5.0-megadalton insert of viral DNA, type II clones contained phage with two size classes of inserts (5.0 and 5.2 megadaltons), and one type III clone contained only a 5.2-megadalton insert. The smaller insert present in type II clones appeared to be derived by deletion of one copy of a directly repeated sequence which was present in the larger insert. Mapping data indicated that the deletion includes all or part of the terminal repeat found in linear double-stranded proviral DNA. Similar results were obtained from lambda RAV2 recombinant clones derived from Rous-associated virus type 2. Analysis of DNA from type II and type III clones of lambda SRBtd and lambda RAV2 revealed limited heterogeneity in the size of the direct repeat. PMID- 6245259 TI - Translational products encoded by newly acquired sequences of independently derived feline sarcoma virus isolates are structurally related. AB - Polyproteins encoded by several independent isolates of feline sarcoma virus (FeSV) were analyzed with respect to molecular weight, extent of phosphorylation, and tryptic peptide composition. As previously reported, cells nonproductively transformed by the Gardner strain of FeSV express a polyprotein which has a molecular weight of approximately 115,000 and contains feline leukemia virus p15, p12, and minor portion of p30. In addition, a major 72,000-dalton possible cleavage product can be identified. Snyder-Theilen FeSV-transformed cells express a major polyprotein of approximately 115,000 daltons and a second highly related 80,000-dalton protein. The p12 structural component of Gardner FeSV P115, but not Snyder-Theilen FeSV 115, corresponds to feline leukemia virus subgroup A with respect to immunological type specificity, a finding consistent with the independent origin of these viruses. Tryptic peptide analysis revealed five methionine-containing peptides specific to the nonstructural portion of Gardner FeSV 115, three of which were also represented in Snyder-Theilen FeSV P115, three of which were also represented in Snyder-Theilen FeSV P115. None of these [35S]methionine-labeled tryptic peptides were present in translational products representative of the complete feline leukemia virus subgroup A genome, including Pr180gag-pol, Pr65gag, and Pr82env. Similarly phosphorylated tryptic peptides within the structural (p12) and nonstructural components of Gardner FeSV P115 and Snyder-Theilen FeSV P115 Are highly related. These findings support the possibility that acquired sequences of two independently derived isolates of FeSV encode structurally related proteins. PMID- 6245260 TI - Integrated Moloney murine leukemia virus DNA studied by using complementary DNA which does not recognize endogenous related sequences. AB - By preannealing a radioactive, representative Moloney murine leukemia virus (M MuLV) cDNA with large excesses of AKR 70S viral RNA, an M-MuLV-specific cDNA has been prepared. When hybridized to restriction enzyme fragments of M-MuLV-infected mouse cell DNA, the preannealed probe recognizes integrated M-MuLV DNA and does not recognize endogenous related DNA sequences found in uninfected mouse cells. The viral DNA sequences recognized by the preannealed probe are spread throughout the viral genome, although some sequences are recognized less efficiently. By using this preannealed probe, multiple integrations of M-MuLV DNA have been detected in infected fibroblasts and in an M-MuLV-induced tumor. Integrated viral DNA fragments smaller than the complete viral genome have also been detected. By using this preannealed probe to examine a mass-infected culture of mouse fibroblasts, no evidence for a strongly preferred site for M-MuLV integration could be found. PMID- 6245261 TI - Transcriptional activities of different phosphorylated species of NS protein purified from vesicular stomatitis virions and cytoplasm of infected cells. AB - Vesicular stomatitis virus contains a phosphorylated NS protein which is necessary along with L protein and RNP template for transcription of mRNA. To further define the structure of the NS protein and its function in transcription and replication, virion NS was purified and separated into two different phosphrylated forms (NSI and NSII) on DEAE-cellulose columns. Cytoplasmic preparations of NS contained one phosphorylated species which eluted from the column in the same place as the virion NSI. When electrophoresed in sodium dodecyl sulfate-polyacrylamide gels containing urea, NSI and NSII each resolved into two components, whereas cell NS migrated as a single band. NSI and cell NS exhibited little activity in a reconstituted transcription assay, whereas the more highly phosphorylated NSII was very active in the same system. Addition of NSI or cell NS to a transcription system containing NSII resulted in even higher levels of activity, indicating that the various NS species might have different enzymatic functions. PMID- 6245262 TI - In vitro transcription and translation of simian rotavirus SA11 gene products. AB - Rotavirus gene products were examined, with the simian rotavirus SA11 as a model. The endogenous viral RNA-dependent RNA polymerase associated with single-shelled virus particles or with activated double-shelled particles was used to synthesize viral RNA transcripts. Sedimentation velocity sucrose gradient analysis of the RNA transcripts revealed four peaks at 9S, 12S, 14S, and 18S, whereas agarose gel electrophoresis under partially denaturing conditions revealed eight groups of RNA species ranging in molecular weight from 2 x 10(5) to 1.2 x 10(6). The transcripts synthesized in vitro were active in an mRNA-dependent cell-free translation system derived from rabbit reticulocytes. The transcripts directed the synthesis of 11 polypeptides that had molecular weights ranging from 125,000 to 20,000 when analyzed by electrophoresis in sodium dodecyl sulfate polyacrylamide gels. The products of in vitro translation were compared with polypeptides from purified virus and those synthesized in infected cells. Several of the polypeptides synthesized in vitro were designated as structural polypeptides by comparing the molecular weights determined by polyacrylamide gel electrophoresis analysis or by precipitation with hyperimmune serum prepared against purified virus. Three of the viral structural polypeptides (VP4, -5, and 5a) were not synthesized in vitro as primary gene products, demonstrating that processing must occur for the production of some structural polypeptides. Other in vitro-synthesized polypeptides were tentatively identified as either precursors to the viral glycoproteins or nonstructural polypeptides. PMID- 6245263 TI - Heavy and light particles of adeno-associated virus. AB - KB cells coinfected with adenovirus and adeno-associated virus (AAV) yielded two kinds of infectious AAV particles that banded in CsCl at densities of 1.45 and 1.41 g/cm(2), respectively. The 1.45 band was found to be composed of a heterogeneous group of viral particles that could be subfractionated by velocity sedimentation. The main component from this band had a smaller S value (109) than the main component from the 1.41 band (111S), although both had the same DNA/protein ratio and the same density in metrizamide gradients. Continuous-label experiments showed that early after infection, both components (1.45 and 1.41) were generated in the same amounts, but this was followed by a relative increase in the proportion of the 1.41 component over the 1.45 particles. Pulse-chase analysis failed to demonstrate a precursor-product relationship between these two bands. The slower-sedimenting components from the 1.45 band were unstable in CsCl and were present in a greater proportion early after infection. These particles contained DNA that was enriched for the terminal sequences of the AAV genomes and was accessible to digestion with micrococcal nuclease. PMID- 6245264 TI - Late modifications of simian virus 40 chromatin during the lytic cycle occur in an immature form of virion. AB - Two main modifications of the simian virus 40 chromatin were found to occur during the lytic cycle. One was the progressive increase in the acetylation level in the four non-H1 histones as the 75S deoxynucleoprotein complexes (minichromosomes) became assembled into heavier structures. The other was the final elimination from viral chromatin of histone H1. An important stage in the course of these changes was represented by an intracellular simian virus 40 particle, in which the virus-coded proteins were already assembled, but properties distinct from those of mature virions were still present. This particle resembled the mature virions in morphology, sedimentation rate, and buoyant density. It was distinguished by the instability, the presence of histone H1, the uptake of radioactive acetate, and the lower infectivity. Its significance appears to be that of an immature virion on the basis of these characters and of the consistent kinetic behavior during the lytic cycle. PMID- 6245265 TI - Replication of herpesvirus DNA. V. Maturation of concatemeric DNA of pseudorabies virus to genome length is related to capsid formation. AB - The maturation of pseudorabies virus DNA from the replicative concatemeric form to molecules of genome length was examined using nine DNA+ temperature-sensitive mutants of pseudorabies virus, each belonging to a different complementation group. At the nonpermissive temperature, cells infected with each of the mutants synthesized concatemeric DNA. Cleavage of the concatemeric DNA to genome-length viral DNA was defective in all the DNA+ ts mutants tested, indicating that several viral gene products are involved in the DNA maturation process. In none of the ts mutant-infected cells were capsids with electron-dense cores (containing DNA) formed. Empty capsids with electron-translucent cores were, however, formed in cells infected with six of the nine temperature-sensitive mutants; in cells infected with three of the mutants, no capsid assembly occurred. Because these three mutants are deficient both in maturation of DNA and in the assembly of viral capsids, we conclude that maturation of viral DNA is dependent upon the assembly of capsids. In cells infected with two of the mutants (tsN and tsIE13), normal maturation of viral DNA occurred after shiftdown of the cells to the permissive temperature in the presence of cycloheximide, indicating that the temperature-sensitive proteins involved in DNA maturation became functional after shiftdown. Furthermore, because cycloheximide reduces maturation of DNA in wild-type-infected cells but not in cells infected with these two mutants, we conclude that a protein(s) necessary for the maturation of concatemeric DNA, which is present in limiting amounts during the normal course of infection, accumulated in the mutant-infected cells at the nonpermissive temperature. Concomitant with cleavage of concatemeric DNA, full capsids with electron-dense cores appeared after shiftdown of tsN-infected cells to the permissive temperature, indicating that there may be a correlation between maturation of DNA and formation of full capsids. The number of empty and full capsids (containing electron-dense cores) present in tsN-infected cells incubated at the nonpermissive temperature, as well as after shiftdown to the permissive temperature in the presence of cycloheximide, was determined by electron microscopy and by sedimentation analysis in sucrose gradients. After shiftdown to the permissive temperature in the presence of cycloheximide, the number of empty capsids present in tsN-infected cells decreased with a concomitant accumulation of full capsids, indicating that empty capsids are precursors to full capsids. PMID- 6245266 TI - Purification of Theiler's murine encephalomyelitis virus and analysis of the structural virion polypeptides: correlation of the polypeptide profile with virulence. AB - Theiler's murine encephalomyelitis viruses (TMEV) are separable into two groups based on their biological behavior: those highly virulent isolates which are unable to cause persistent infection and the less virulent isolates which regularly produce persistent central nervous system infection in mice. Two highly virulent and five less virulent TMEV were found to have the same buoyant density (1.34 g/ml) on isopycnic centrifugation and virion structure by electron microscopy. Negatively stained virus particles purified in Cs(2)SO(4) gradients appeared to have icosahedral symmetry and measured 28 nm in diameter. Mature virions were found to possess three major structural polypeptides, VP1, VP2 and VP3, in the range of 25,000 to 35,000 daltons, and a smaller fourth major polypeptide, VP4, of 6,000 daltons on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The precursor of VP2 and VP4, VP0, which is a minor polypeptide of mature picornavirus particles, was also identified. However, a slight but consistent difference in several of the capsid polypeptides between the highly virulent and less virulent TMEV was found. VP1 was slightly larger (34,000 versus 33,500 daltons) and VP2 was slightly smaller (31,000 versus 32,000 daltons) for the highly virulent strains compared to the same polypeptide species in the less virulent viruses. VP0 was also slightly smaller (35,500 versus 36,000 daltons) for the highly virulent isolates compared to their less virulent counterparts. Finally, trypsin which was used initially in our purification procedure resulted in preferential cleavage of a 2,000-molecular-weight fragment or fragments from VP1 of only the less virulent isolates. PMID- 6245267 TI - Isolation and characterization of polyoma uncoating intermediates from the nuclei of infected mouse cells. AB - A method was developed which enabled the efficient recovery of polyoma uncoating intermediates from the nuclei of infected cells at early times after infection (15 min to 12 h). Cells were infected with radiolabeled virus and lysed with the detergent Nonidet P-40. The nuclei were then collected and sonicated, and the products were analyzed on sucrose gradients. The uncoating intermediate sedimented at 190S and was a viral DNA-protein complex closely associated with a structure of host origin. The host material associated with the 190S uncoating intermediate was determined by polyacrylamide gel electrophoresis and visualized by electron microscopy. The amount of 190S uncoating intermediate found in the nucleus increased with time after infection. The viral DNA was predominantly for I. All of the viral proteins were present in the 190S uncoating intermediate in amounts similar to those found in viral DNA-protein complex cores. PMID- 6245268 TI - Simian virus 40 small-t protein is required for loss of actin cable networks in rat cells. AB - The ability of the two early simian virus 40 (SV40) coded proteins, the large and small T-antigens, to abortively induce the disappearance of cytoplasmic actin containing networks in cultured cells has been studied in rat embryo fibroblasts after microinjection of intact SV40 DNA, DNA fragments from the early region of SV40, and a purified SV40 large T-antigen related protein (the D2 hybrid protein) isolated from cells infected with the adenovirus-SV40 hybrid virus Ad2+D2. Injection of either the 107,000-dalton D2 hybrid protein or SV40 DNA from the deletion mutant dl 884 SV40, which lacks part of the region (0.54 to 0.59) encoding small t-antigen, failed to cause any detectable change in the structure of actin cables in recipient cells over a period of 72 h. By contrast, injection of wild-type SV40 DNA or a DNA fragment containing the entire region coding for a small-t antigen leads to the disruption of actin cable networks within 24 h of injection. It appears likely that the SV40 small-t protein is necessary for the abortive loss of actin cables in injected cells. Epidermal growth factor also causes loss of actin cables in rat embryo fibroblasts or Rat 1 cells (an established rat embryo line), but only after exposure of the cells to epidermal growth factor in the culture medium and not after injection of epidermal growth factor into the cells. PMID- 6245269 TI - Ultrastructural characterization of an early, nonstructural polypeptide of herpes simplex virus type 1. AB - An immunoperoxidase procedure was employed to study the expression of a large molecular-weight, virus-induced polypeptide (VP175; molecular weight, 175,000) at the light and electron microscopic levels in Vero cells infected with herpes simplex virus type 1 or with tsB2, a DNA-negative, temperature-sensitive mutant of herpes simplex virus type 1. In cells infected with herpes simplex virus type 1 and in cells infected with tsB2 at the permissive temperature (34 degrees C), VP175 was found within the nucleus. The protein was detected as early as 2 h postinfection and, by 3 h postinfection, was generally distributed in a marginated pattern contiguous with, and extending from, the inner lamella of the nuclear membrane. At 6 h postinfection, protein accumulations were dispersed throughout the nucleus, and, by 9 h postinfection, these accumulations tended to be localized in a marginated pattern near the nuclear membrane. It was also noted that, at 9 h postinfection, under permissive conditions, VP175 was not found in association with nucleocapsids or enveloped particles. In contrast, in cells infected with tsB2 at the nonpermissive temperature (39 degrees C) and harvested at 6 or 9 h postinfection, accumulations of VP175 were identified not only within the nucleus, but also within the cytoplasm in the form of annular or globular aggregates. These aggregates consisted of a granular matrix and were not bound by membranes. PMID- 6245270 TI - Transfection by DNAs of avian erythroblastosis virus and avian myelocytomatosis virus strain MC29. AB - Chicken embryo fibroblasts and NIH 3T3 mouse cells were transformable by DNAs of chicken cells infected with avian myelocytomatosis virus strain MC29 or with avian erythroblastosis virus. Transfection of chicken cells appeared to require replication of MC29 or avian erythroblastosis virus in the presence of a nontransforming helper virus. In contrast, NIH 3T3 cells transformed by MC29 or avian erythroblastosis virus DNA contained only replication-defective transforming virus genomes. PMID- 6245271 TI - Variable defectiveness for lytic growth of the dl 54/59 mutants of simian virus 40. AB - When viral growth in TC-7 cells is compared with that in the simian virus 40 (SV40) transformed CV-1 line C6 some mutants of SV40 deleted between 0.54 and 0.59 on the standard map (dl 54/59 mutants) give relative bursts similar to those of wild-type strain 776, whereas others grow markedly poorer in the untransformed cell. In general, viruses which are defective by this criterion have been found to produce neither a fragmentary small-t protein nor a mature small-t mRNA. PMID- 6245272 TI - Viable deletion mutant in the medium and large T-antigen-coding sequences of the polyoma virus genome. AB - A polyoma virus mutant that maps in the early region between the known hr-t and ts-a mutants has been isolated. Its 66-base-pair deletion results in structural changes in both medium and large T-antigens but causes no substantial alterations in viral replication or cell transformation. PMID- 6245273 TI - Location and cloning of the herpes simplex virus type 2 thymidine kinase gene. AB - The herpes simplex virus type 2 thymidine kinase gene has been mapped to a position colinear with the herpes simplex virus type 1 thymidine kinase gene and cloned within a 4.0-kilobase fragment in pBR 322. PMID- 6245274 TI - Integration pattern of human JC virus sequences in two clones of a cell line established from a JC virus-induced hamster brain tumor. AB - The physical state of the JC virus (JCV) genome was studied in two clonal cell lines (clones 2 and 7) derived from a tissue culture cell line (HJC-15) established from a hamster brain tumor induced by JCV. Saturation-hybridization and reassociation kinetic analyses, using in vitro (32)P-labeled JCV DNA, indicated that clone 7 and 2 cells contain 9 to 10 and 4 to 5 copies per cell, respectively, of all or most of the viral genome. Both cell DNAs were analyzed by using the Southern blotting procedure with three restriction endonucleases: XhoI, which does not cleave JCV DNA; EcoRI, which cleaves once; and HindIII, which cleaves three times. With each DNA, a variety of JCV-specific DNA fragments were detected. The following conclusions are possible: (i) JCV DNA is integrated into cell DNA in both clonal lines; (ii) both clonal lines contain multiple copies of the viral genome integrated in a tandem head-to-tail orientation; (iii) neither clonal line contains detectable free-form I, II, or III JCV DNA; (iv) each clonal line contains multiple independent sites of JCV DNA integration; and (v) most or all of the sites of integration on the cellular or the viral genome, or both, are different in clone 7 DNA than in clone 2 DNA. Thus, although both clone 7 and clone 2 cells were established from the HJC-15 tumor cell line, they differ in the copy number and integration pattern of JCV DNA. PMID- 6245275 TI - Distribution of endogenous murine leukemia virus DNA sequences among mouse chromosomes. AB - We used mouse-Chinese hamster somatic cell hybrids which lose mouse chromosomes to examine the distribution of murine leukemia virus DNA sequences in the genome of A/HeJ mice. We analyzed total cellular DNA from various hybrid clones for the presence of viral sequences by molecular hybridization and used the Southern blot hybridization procedure to identify viral DNA in cellular restriction endonuclease fragments. Our results show that murine leukemia virus DNA sequences are distributed among many mouse chromosomes in this strain. Chromosome 4 was shown to contain murine leukemia virus DNA sequences. PMID- 6245276 TI - Transcription of polyoma DNA by Escherichia coli RNA polymerase: influence of ionic strength on promoter selection. AB - The influence of ionic strength on transcription of polyoma DNA by Escherichia coli RNA polymerase was investigated. At 0.15 M KCl, transcription was highly symmetrical and, due to the lack of reinitiation, a limited extent of RNA synthesis was observed. When the concentration of KCl was raised to 0.45 M, the affinity of the enzyme for its template, as well as its apparent affinity for ribonucleoside triphosphates, was reduced. Under optimal conditions, the rate and extent of RNA synthesis at 0.45 M KCl were greater than at 0.15 M KCl, and transcription was mostly asymmetric. Binding and initiation sites at both ionic strengths were identified; at 0.15 M KCl, transcription was initiated from two major sites, located at 0.99 and 0.06 map unit, whereas at 0.45 M KCl, a unique initiation site, at 0.99 map unit, was selected by RNA polymerase. PMID- 6245277 TI - Avian retroviruses that cause carcinoma and leukemia: identification of nucleotide sequences associated with pathogenicity. AB - Avian myelocytomatosis virus (MC29V) is a retrovirus that transforms both fibroblasts and macrophages in culture and induces myelocytomatosis, carcinomas, and sarcomas in birds. Previous work identified a sequence of about 1,500 nucleotides (here denoted onc(MCV)) that apparently derived from a normal cellular sequence and that may encode the oncogenic capacity of MC29V. In an effort to further implicate onc(MCV) in tumorigenesis, we used molecular hybridization to examine the distribution of nucleotide sequences related to onc(MCV) among the genomes of various avian retroviruses. In addition, we characterized further the genetic composition of the remainder of the MC29V genome. Our work exploited the availability of radioactive DNAs (cDNA's) complementary to onc(MCV) (cDNA(MCV)) or to specific portions of the genome of avian sarcoma virus (ASV). We showed that genomic RNAs of avian erythroblastosis virus (AEV) and avian myeloblastosis virus (AMV) could not hybridize appreciably with cDNA(MCV). By contrast, cDNA(MCV) hybridized extensively (about 75%) and with essentially complete fidelity to the genome of Mill Hill 2 virus (MH2V), whose pathogenicity is very similar to that of MC29V, but different from that of AEV or AMV. Hybridization with the ASV cDNA's demonstrated that the MC29V genome includes about half of the ASV envelope protein gene and that the remainder of the MC29V genome is closely related to nucleotide sequences that are shared among the genomes of many avian leukosis and sarcoma viruses. We conclude that onc(MCV) probably specifies the unique set of pathogenicities displayed by MC29V and MH2V, whereas the oncogenic potentials of AEV and AMV are presumably encoded by a distinct nucleotide sequence unrelated to onc(MCV). The genomes of ASV, MC29V, and other avian oncoviruses thus share a set of common sequences, but apparently owe their various oncogenic potentials to unrelated transforming genes. PMID- 6245278 TI - Coding assignments of double-stranded RNA segments of SA 11 rotavirus established by in vitro translation. AB - The segmented double-stranded (ds) RNA genome of the simian rotavirus SA 11, after denaturation, can be translated in a cell-free protein synthesizing system. Of the 11 genome segments, 9 can be resolved on polyacrylamide gels and thus could be individually isolated and translated, providing a means of identifying the polypeptide encoded by each segment. On the basis of electrophoretic mobility of products in sodium dodecyl sulfate-polyacrylamide gels, the probable gene coding assignments of dsRNA segments 1 to 6 were determined. RNA segments 1 to 4 code for polypeptides I1, I2, I3, and I4, respectively; segment 5 codes for a polypeptide very similar in mobility to a minor polypeptide present in SA 11 infected cells, O1A; and segment 6 codes for the major inner-capsid polypeptide I5. PMID- 6245279 TI - env Gene of Rous sarcoma virus: identification of the gene product by cell-free translation. AB - Cell-free translation of polyadenylic acid-selected, denatured virion 70S RNA of the Schmidt-Ruppin strain of Rous sarcoma virus (subgroup A) yields a 64,000-Mr polypeptide which is specifically immunoprecipitated by a group-specific serum raised against envelope glycoprotein gp85. This polypeptide is not synthesized from the virion RNA of the replication-defective mutant rdNY8SR-A, which contains an extensive deletion within the envelope (env) gene. From this genetic evidence we conclude that the 64,000-Mr polypeptide represents the nonglycosylated product of the env gene and propose the designation of P64env. The 64,000-Mr polypeptide is translated from a 26S to 28S polyadenylated RNA species, whereas the p60src product is synthesized from a 20S to 22S RNA, and both Pr76gag and P180gag-pol are synthesized predominately from 34S RNA. The product of the env gene of Rous associated virus-2 was also identified by cell-free translation. PMID- 6245280 TI - Appendiceal carcinoma mimicking primary bladder cancer. AB - We report the first case of adenocarcinoma of the appendix invading the bladder. Because invasive bladder cancer was diagnosed intially the pelvis was irradiated preoperatively. At operation a primary appendiceal neoplasm invading the bladder was discovered and a right hemicolectomy and en block partial cystectomy were done. This treatment is recommended for appendiceal adenocarcinoma that invades the bladder. PMID- 6245281 TI - Postoperative intussusception. AB - When an apparently favorable postoperative course is suddenly complicated by intestinal obstruction intussusception must be considered as the most likely cause. Four cases of intussusception after genitourinary operations are presented. PMID- 6245282 TI - Enucleative surgery for a renal tumor in a solitary kidney. PMID- 6245283 TI - Clostridium perfringens as a water pollution indicator. PMID- 6245284 TI - Fatal monomucleosis? don't rule it out. PMID- 6245285 TI - Registry of fatal infectious mononucleosis and Epstein-Barr virus infections. PMID- 6245286 TI - Visceral herpesvirus infections in leukemic patients receiving cytarabine. AB - Autopsy evidence of herpesvirus infection was found in visceral organs of four leukemic patients who had received large doses of cytarabine (cytosine arabinoside; Ara-C) shortly before their death. In three of these patients the infection was clinically unsuspected; in the fourth, cutaneous herpes zoster developed after administration of 300 mg of cytarabine daily for the preceding five days. Although cytarabine exhibits pronounced in vitro virucidal activity against herpes viruses and has been successfully used in clinical treatment of severe herpesvirus infections, the present findings and a review of the recent literature cast doubt on the antiviral effectiveness of this drug, particularly in already immunosuppressed patients, and suggest instead that such patients actually have an increased risk for development of disseminated herpesvirus infection owing to further depression of host defenses by the drug. PMID- 6245287 TI - Cholesteryl ester-rich lipid inclusions from human aortic fatty streak and fibrous lesions of atherosclerosis. II. Physical properties of swelling, resiliency and lyotropy as liquid crystal. AB - The physical properties of the lipids accumulating as spherical inclusions in human atherosclerotic lesions were explored both in vivo and in vitro conditions. They were mostly anisotropic within the cytoplasma of cells and in an average diameter of 1.96 mu. When suspended in hydrophilic media, say of physiological saline solution, in 4 hours they swelled 2.4 times in volume and changed into isotropic form. They were resilient and deformable in three dimensional configuration, and lyotropic in polar media. When dried they underwent a phase shifting from liquid crystal to true solid crystal. These physical properties of lipid inclusions gained in a new significance for their role in metabolic deterioration of intima cells, rupture and necrosis of foam cells, and destruction of the intimal and medial architectures, which set on mesenchymal reactions leading eventually to thickening and hardening of the arteries. PMID- 6245288 TI - Chemotherapy of atherosclerosis. AB - Clinical and experimental studies have provided an increasing amount of evidence that atherosclerosis is preventable and that regression is feasible. Although the elimination of risk factors would be a form of primary prevention such is hardly feasible in our modern industrial age. Thus the combination of elimination or at least decrease in risk factors and a direct treatment of the arterial wall should help to bring about this prevention and regression. Metabolic changes and/or dysfunction of the vessel wall particularly endothelial cells has been given increasing attention. Energy and cyclic nucleotide metabolism in endothelial cells have been studied in the initiation, progression and regression of atherosclerosis. Several compounds were found to exert beneficial effects on metabolism in the endothelial cells and clinical favorable effects have been documented. Chemotherapy for the treatment of "endotheliopathy" and atherosclerosis will not doubt be the object of intensive studies. PMID- 6245289 TI - Effect of hypothermia during ischemia on myocardial contractility in nonhypertrophied and hypertrophied ventricles. AB - The effect of hypothermic ischemic arrest on myocardial contractility was investigated with use of isolated blood-perfused canine heart preparation in the hypertrophied left ventricle created by supravascular aortic stenosis and the non hypertrophied ventricle. The following results were obtained: The percent recovery rate of net developed tension during reperfusion after an ischemic period of 150 minutes at the myocardial temperature of 17 degrees C was 90 +/- 9% in the non-hypertrophied muscle, that is, hypertrophied left ventricle was considered to be more vulnerable to ischemia as compared to nonhypertrophied left ventricle, suggesting the necessity of more intense myocardial protection in addition to cardiac hypothermia against ischemia in the hypertrophied heart. PMID- 6245290 TI - [Study of neuromuscular transmission with evoked electromyography. Correlation between extent of curarization and train-of-four ratio (author's transl)]. PMID- 6245291 TI - The effects of dilazep and SG 75 on cyclic nucleotides in the coronary artery. AB - We examined the effects of new long acting coronary vasodilators (dilazep and SG 75) on cyclic nucleotides in the coronary artery and the myocardium at the maximum coronary blood flow. The cyclic AMP concentrations in the anterior descending coronary artery after the injection of saline (control), SG 75 (0.2 mg/Kg), and dilazep (0.1 mg/Kg) were 229 +/- 20 pmole/Gm, 249 +/- 21 pmole/Gm, and 320 +/- 21 pmol/Gm, respectively. A significant increase above control values was found in the dilazep treated group (p less than 0.02). The cyclic GMP concentrations in the coronary artery after the injection of saline, SG 75, and dilazep were 35.6 +/- 4.4 pmole/Gm, 40.4 +/- 3.3 pmole/Gm, 35.3 +/- 3.2 pmole/Gm, respectively. There were no significant differences between them. The cyclic AMP and cyclic GMP concentrations in the left ventricular muscle did not significantly increase after the administration of dilazep and SG 75. Our findings showed that the mechanism of coronary vasodilating action of dilazep might be associated with an increased cyclic AMP in the coronary artery. PMID- 6245292 TI - [Pathology of trophoblastic disease with special reference to carcinogenesis and maternal extension of gestational choriocarcinoma (author's transl)]. PMID- 6245293 TI - [Angiographic findings of magnification bronchial arteriography in pulmonary carcinoma (author's transl)]. PMID- 6245294 TI - [Evaluation of measurement of serum angiotensin-converting enzyme (S-ACE) level in sarcoidosis (author's transl)]. PMID- 6245295 TI - Evaluation of syncytium assay for bovine leukemia virus. PMID- 6245296 TI - Bovine leukemia virus infection in Japan: antibody and virus detection in cattle. PMID- 6245297 TI - Hybridization of a myeloid leukemia-derived human cell line (K562) with a human Burkitt's lymphoma line (P3HR-1). AB - The myeloid leukemia-derived Epstein-Barr virus (EBV)-negative human lymphoid cell line K562 was successfully hybridized with the EBV-carrying Burkitt's lymphoma line P3HR-1. Authenticity of the hybrid PUTKO-1 was established by chromosome and isoenzyme studies. A virtually complete hybrid PUTKO-1 carried the EBV genome derived from the lymphoma parent. It averaged 26 EBV DNA copies per cell and was 100% positive for Epstein-Barr virus-associated nuclear antigen (EBNA). In most respects, the hybrid resembled the K562 parent: It had a high Fc receptor concentration, high sensitivity to natural killer cells, absence of EBV C3 receptors, and deficiency of membrane-associated beta 2-microglobulin (beta 2M) and HLA, in parallel with intracellular synthesis and secretion of beta 2M to the medium. Unlike the P3HR-1 parent, the hybrid was completely nonpermissive for antigens of the EBV cycle, early antigen, and viral capsid antigen. None of the 3 inducing agents, 5-lodo-2'-deoxyuridine, 12-O-tetradecanoyl-phorbol 13-acetate, or sodium butyrate, caused any viral antigen synthesis in PUTKO-1 in contrast to the good inducibility of the parental P3HR-1 subline. Thus the myeloid parent restricted expression of EBV antigens except EBNA. This exception further supports the concept that EBNA is an autonomous function of the viral genome, independent of host cell control that regulates expression of antigens related to the viral cycle. On the contrary, extinction of viral antigens in this hybrid between 2 cell lineages supports our previous concept that the ability to produce viral antigens is similar to a differentiated B-cell property. PMID- 6245298 TI - Virus-induced cellular immunity to simian virus 40 tumor-specific surface antigen(s) in adult LVG:LAK hamsters. AB - Cell-mediated immunity directed against simian virus 40 (SV40) tumor-specific surface antigen(s) (TSSA) was detected in SV40-immunized noninbred LVG:LAK hamsters with the use of a lymphocyte transformation assay. Sensitized spleen cells underwent a proliferative response in the presence of cells of an SV40 induced hamster sarcoma cell line (WF5-1) or the plasma membranes from these cells. In addition, 3-M KCl extracts of the plasma membranes of WF5-1 cells elicited such a lymphocyte proliferative response. Neither the cells of a chemically induced sarcoma cell line (OBT), their plasma membranes, nor 3-M KCl extracts of these membranes caused a similar proliferative response. These results established that immunization of adult hamsters with SV40 resulted in a specific autochthonous cell-mediated immune response against SV40 TSSA. The in vitro demonstration of this virus-induced immunity provided a unique method for the investigation of the SV40 TSSA involved in the establishment or rejection of tumors. The described lymphocyte transformation assay was also used to follow the solubilization and purification of the SV40 TSSA. PMID- 6245299 TI - Characterization of tumorigenic and metastatic properties of murine sarcoma virus transformed nonproducer Balb/3T3 cell lines. PMID- 6245300 TI - Attempt to infect nonmalignant nasopharyngeal epithelial cells from humans and squirrel monkeys with Epstein-Barr virus. AB - With the use of Epstein-Barr virus (EBV), attempts were made to infect epithelial nasopharyngeal explant cell cultures prepared from nonmalignant human and squirrel monkey tissue. Explants were exposed to EBV from both HR-1 and B95-8 cells and examined for EBV-specific antigens by immunofluorescence and electron microscopy. Among the human specimens, no epithelial nasopharyngeal were found that could be infected with EBV. However, similar explants derived from squirrel monkey tissue were infected. The results were consistent with the hypothesis that EBV can infect at least certain explanted epithelial cells of the nasopharynx. PMID- 6245301 TI - Naturally occurring leukemia viruses in H-2 congenic C57BL mice. I. High lymphoma incidence following milk-borne transmission of virus. AB - Two modes of transmission of ecotropic type C viruses occur naturally in C57BL mice: maternal (i.e., through milk) and genetic. By selection of virus-positive and virus-negative B10.ASgSn [B10.A (H-2a)] mothers and foster-nursing of C57BL/10ScSn [B10 (H-2b)] newborns, four sublines of C57BL mice were obtained: B10.A V+, B10.A V-, B10 V+, and B10 V-. (V+ denotes positive for milk-transmitted B-tropic virus; V- denotes negative for milk-transmitted B-tropic virus). Milk transmission of naturally prevalent B-tropic virus (V+ sublines) led to persistent infection of all offspring over at least 8 generations. Milk transmission of virus was associated with a very high incidence of lymphomas. The H-2 complex influenced the titers of virus after milk transmission, which were higher in B10.A V+ mice than in B10 V+ mice. H-2 control of virus titers, as measured by serum p30 assay, was confirmed in (B10.A V+ X B10 V+)F2 mice. Resistance to the virus was dominant, because serum p30 levels in F1 and H-2a/b F2 animals were similar to those in the B10 V+ subline and lower than those in the B10.A V+ subline. The H-2 complex also influenced the incidence of lymphomas (78 and 42%, respectively, in the B10.A V+ and B10 V+ sublines). Most B10.A V+ lymphomas were of T-cell origin, whereas most B10 V+ lymphomas were classified as non-T/non-B cells. Genetic transmission of virus (V- sublines) led to heterogeneous expression of both N- and B-tropic viruses, which thereby established the mottled trait for expression of genetically transmitted type C viruses in C57BL mice. Genetic transmission was associated with a low incidence of lymphomas that occurred in senescence. PMID- 6245302 TI - Naturally occurring leukemia viruses in H-2 congenic C57BL mice. II. Antibody response to viral envelope antigens. AB - In C57BL mice milk-borne infection with B-tropic murine leukemia virus (V+ denoting positive for milk-transmitted B-tropic virus and V- denoting negative for milk-transmitted B-tropic virus) was accompanied by an antibody response against viral envelope antigens (VEA). Milk transmission of virus led to higher virus titers and lymphoma incidence in B10.A (H-2a) mice than in B10 (H-2b) mice, and the latter strain produced higher titers of anti-VEA antibodies than did the former. H-2 control of the antivirus-antibody response was confirmed in the (B10.A V+ X B10 V+)F2 cross. B10 V+ mice produced both IgM and IgG antibodies, whereas in the sera of B10.A V+ mice only IgM antibodies were demonstrable. The production of IgG and high-titer IgM antibodies to VEA was dominant in (B10.A V+ X B10 V+)F1 animals. The failure of B10.A V+ mice to produce IgG antibodies against VEA was not due to an intrinsic defect of helper T-cell function because these mice produced IgG antivirus antibodies after sc immunization with killed viral vaccine. Furthermore, in B10.A mice without milk-transmitted virus (B10.A V subline), expression of genetically transmitted virus upon aging was associated with the production of IgG antibodies to VEA. The combined data were compatible with the existence of an H-2-linked dominant immune-response gene regulating the antibody response to milk-transmitted murine leukemia virus. PMID- 6245303 TI - Prevalence and distribution of murine mammary tumor virus antigen detectable by immunocytochemistry in spontaneous breast tumors of wild mice. AB - Mouse mammary tumor virus (MuMTV) antigens were detected by immunoperoxidase cytochemistry in spontaneous breast tumors of wild mice from two widely separated areas of southern California. Eleven of 25 (44%) tumors from Lake Casitas (LC) mice and 4 of 5 tumors from Bouquet Canyon mice were positive. Included among the tumors lacking detectable MuMTV antigen were well-differentiated type A and type B carcinomas as well as tumors with an atypical pattern. In the antigen-positive tumors the distribution of staining was patchy and extremely variable in extent (less than 1-70% stained cells). The intensity and extent of staining were generally greater in breast tumors from hybrids of LC wild mice and C5LBL/10Sn or AKR inbred mice. A good correlation was found in the same tumors between immunoperoxidase staining, detection of MuMTV gp52 antigen by radioimmunoassay, and detection of type B particles by electron microscopy. All of the breast tumors in LC mice were positive for type C virus particles. PMID- 6245304 TI - [Bronchological study, laparoscopy and laparatomy in the more precise diagnosis of lung cancer]. PMID- 6245305 TI - [Low temperature effect on collagenase activity inhibition in experimental corneal burns (author's transl)]. PMID- 6245306 TI - [Parathormone and renal excretion in healthy controls and patients with nephrolithiasis (author's transl)]. AB - Idiopathic nephrolithiasis with recurrent ca-oxalat stones are investigated for occult renal dysfunction or for disturbed clearance of PTH. After injection of PTE a significant increase of renal excretion of Na+, K+, Ca2+ and uric acid was observed normalizing within 120 min after injection. Healthy controls showed similar changes, and following PTH the cAMP generating capacity of patients with recurrent stones was in normal range. The turn over rate of PTH was 30-40 min without differences in the collectives studied. PMID- 6245307 TI - A progressive axonopathy of Boxer dogs affecting the central and peripheral nervous systems. PMID- 6245308 TI - A case report: a conjunctivocorneal papilloma with evidence of a viral etiology. PMID- 6245309 TI - Susceptibility to diabetogenic virus: host versus pancreatic factors. PMID- 6245310 TI - Oncology Grand Rounds. Small cell lung cancer and paraneoplastic syndromes. PMID- 6245311 TI - Cooperative response of chemically excitable membrane. II. Two-state models and their limitations. PMID- 6245312 TI - Fixation of cellular aging processes by SV40 virus transformation. PMID- 6245313 TI - [Gas gangrene caused by bacteria, other than Clostridium, and diabetes mellitus. A study of two cases (author's transl)]. PMID- 6245314 TI - Electrolyte excretion in alcohol preferring and alcohol avoiding rats. PMID- 6245315 TI - The effect of prostacyclin on intestinal ion transport in the rat. PMID- 6245316 TI - The effect of 4-hydroxy-2, 3-trans-pent-en-1-al and maleylaldehyde on some mitochondrial functions. PMID- 6245317 TI - Differential supersensitivity of beta-receptor subtypes in rat cortex and cerebellum after central noradrenergic denervation. PMID- 6245318 TI - Effects of exogenous adenosine deaminase and erythro-9-(2-hydroxy-3-nonyl) adenine on intracellular cyclic AMP levels in C1300 murine neuroblastoma in tissue culture. PMID- 6245319 TI - Opioid peptides. PMID- 6245320 TI - Interactions of taurine and beta-alanine with central nervous system neurotransmitter receptors. PMID- 6245321 TI - Normal copper metabolism in quaking mice. PMID- 6245322 TI - [A survey of schistosomiasis in Ivory Coast (author's transl)]. AB - S. intercalatum has not yet been observed in Ivory Coast whereas S. mansoni and S. haematobium are frequent. S. mansoni schistosomiasis is distributed in limited foci as a consequence of the vital requirements of Biomphalaria. Its clinical detection is uneasy and stool control is necessary. Kato's technique is recommended. Prevalence has great topographic variations with an average value of 0,7 p. 100. Complications are not frequent, and can be detected only with rather sophisticated techniques available only in hospital. S. haematobium schistosomiasis is much more widespread according to the strong resistence of the mollusc host. Its clinical syndrome is significant and the diagnosis is easily controlled by a microscopic examination of the urine centrifugation deposit. The average prevalence is about 20-25 p. 100. Detection of complication requires hospital equipments. PMID- 6245323 TI - [Epidemiological survey on splenomegalies in areas of endemic S. mansoni schistosomiasis (author's transl)]. PMID- 6245324 TI - [Cytomegalic inclusion disease in the newborn and in the adult]. PMID- 6245325 TI - [Pivmecillinam in the treatment of urinary tract infections. Clinical effects and side effects]. PMID- 6245326 TI - [Treatment of thyroid diseases II]. PMID- 6245327 TI - Cellular retinol-, retinal-, and retinoic acid-binding proteins from bovine retina. PMID- 6245328 TI - Gas--liquid chromatographic determination of vitamin D in multiple vitamin tablets and their raw materials. PMID- 6245329 TI - Gas--liquid chromatographic determination of vitamin D. PMID- 6245330 TI - High-performance liquid chromatographic determination of vitamin D and metabolites. PMID- 6245331 TI - Determination of vitamin D and its metabolites in plasma. PMID- 6245332 TI - Some features of the receptor proteins for the vitamin D metabolites. PMID- 6245333 TI - Measurement of kinetic rate constants for the binding of 1 alpha, 25 dihydroxyvitamin D3 to its chick intestinal mucosa receptor using a hydroxyapatite batch assay. PMID- 6245334 TI - Structural aspects of the binding of 1 alpha, 25-dihydroxyvitamin D3 to its receptor system in chick intestine. PMID- 6245335 TI - Characteristics and purification of the intstinal receptor for 1,25 dihydroxyvitamin D. PMID- 6245336 TI - Structural organization of mouse rDNA: comparison of transcribed and non transcribed regions. AB - The DNA of the recombinant phage lambda gtWES Mr974 (GRUMMT et al., 1979) which contains the 18S region and adjacent spacer sequences of the ribosomal genes from mouse has been digested with the restriction endonuclease SalI. Fragments corresponding to the non-transcribed spacer (A and D) and the external transcribed spacer (B) have been prepared and their nucleotide composition and sequence organization has been determined. The data indicate that the part of the non-transcribed spacer contained in Mr974 consists of at least two structural domains of distinct sequence characteristics. Fragment A contains 49% G + C and exhibits a high sequence complexity. Fragment D, the spacer fragment flanking the coding region, is very rich in G + C and is obviously composed of an internally repetitive sequence which is cut by several restriction enzymes into a similar set of repetitive fragments. Most of the fragments have sizes that are multiples of 60 and 80 or 140 base pairs, respectively, suggesting an alternating 60/80bp arrangement. This regular sequence in fragment D accounts both for the observed instability and length heterogeneity of the rDNA insert in several clones and probably for the heterogeneity in the structure of the ribosomal repeats in the genomic DNA. PMID- 6245337 TI - Conversion of bacteriophage fd into an efficient single-stranded DNA vector system. AB - Single-stranded DNA vectors were constructed in vitro by insertion of various DNA fragments into the Intergenic Region of the single-stranded DNA phage fd. These inserts introduce into the phage genome unique cleavage sites for restriction nucleases which are suited for sticky joining in cloning experiments. Since these sites are usually located within genes coding for antibiotic resistance, inactivation of a resistance gene by insertion can be used as a marker for the successful cloning of a DNA fragment. Resistance genes also allow to select for recombinant DNA phages and to minimize the loss of DNA inserts which otherwise becomes significant above an insert size of about one kb. Cloning of several DNA fragments is described and strand separation of double-stranded DNA fragments by means of cloning into fd DNA is given as an example for application of single stranded DNA vectors. PMID- 6245338 TI - A relationship between plasmid structure, structural lability, and sensitivity to site-specific endonucleases in Neisseria gonorrhoeae. AB - Nearly all gonococcal strains carry a small "phenotypically cryptic" plasmid of approximately 4,200 basepairs. A detailed physical map of this plasmid has been constructed, revealing the presence of numerous putative inverted repeats. These studies also revealed the presence on the plasmid of recognition sequences for several site-specific endonucleases (particularly HpaII, MspI and AluI) that are particularly resistant to cleavage, and confirmed previous reports of structural lability. Both the sites that are resistant to cleavage, and the observed structural variation are associated with the inverted repetitive sequences. PMID- 6245339 TI - On the role of IS1 in the formation of hybrids between the bacteriophage P1 and the R plasmid NR1. PMID- 6245340 TI - Transfection of protoplasts from Streptomyces lividans 66 with actinophage SH10 DNA. AB - The slightly modified procedure for the transformation of protoplasts of S. coelicolor A3 (2) with SCP2 plasmid DNA and polyethylenglycol (PEG) (Bibb et al., 1978) was extended to infection of protoplasts of S. lividans 66 with actinophage SH10 DNA (Klaus et al., 1979). Maximal yield of transfected protoplasts was obtained at 20% PEG, 3 MM sodium-citrate and 150 mM NaCl final concentrations. The efficiency of transfection was determined to be about 2 x 10(-8) to 2 x 10( 7). The average value of competent protoplasts was about 1-2 x 10(-4) of regenerating protoplasts. In comparison with outgrowing spores infected with phage particles the average burst size of transfected protoplasts was reduced from 100 to 10 pfu/infected cell, the latent period prolonged from 45 min to 120 min and the rise period was not affected. PMID- 6245341 TI - Requirement of DNA gyrase for the initiation of chromosome replication in Escherichia coli K-12. AB - It has been found that strains carrying mutations in the dnaA gene are unusually sensitive to COU, NAL or NOV, which are known to inhibit DNA gyrase activities. The delay in the initiation of chromosome replication after COU treatment has been observed in cells with chromosomes synchronized by amino acid starvation or by temperature shift-up (dnaA46). The unusual sensitivity of growth to COU of the initiation mutant runs parallel to a higher sensitivity to the drug of the initiation of chromosome replication. The double mutant, dnaA46, cou-110 has been isolated and mutation cou-110 conferring resistance of growth, initiation and elongation of chromosome replication to COU was mapped in the gene coding for the subunit of DNA gyrase. The reduced frequency of appearance of the mutants resistant to COU, NAL, or NOV in the initiation mutant suggests that some mutations in genes coding for DNA gyrase subunits cannot coexist with the dnaA46 mutation. The possible mechanisms of the requirement of DNA gyrase for dnaA dependent initiation of E. coli chromosome are discussed. PMID- 6245342 TI - The construction in vitro of derivatives of bacteriophage lambda carrying the amidase genes of Pseudomonas aeruginosa. AB - The amidase genes of Pseudomonas aeruginosa were inserted into a lambda replacement vector following cleavage with the restriction endonuclease HindIII. The recombinant lambdaami was detected by enhanced growth of Escherichia coli around plaques of the recombinant phage on minimal medium containing acetamide as the nitrogen source. Low levels of amidase activity were detected in E. coli cultures infected with lambdaami and these were sufficient to allow growth with acetamide as nitrogen source. Lysis-defective derivatives of lambdaami were made by introducing Q-, S-, mutations. Cultures of E. coli infected with lambdaamiQ-S- synthesised amidase as the major protein. The amidase produced by these cultures was identical to that produced by PAC strains of P. aeruginosa in substrate specificty, thermal stability and immunological cross-reaction. PMID- 6245343 TI - [Preservation of bacteria that break down alkylsulfates]. PMID- 6245344 TI - [How are hospital patients kept informed after leaving hospital?]. PMID- 6245345 TI - Captopril for hypertension. PMID- 6245346 TI - A summary of responses to cancer therapy in cats. PMID- 6245347 TI - Cranial nerve deficits in a rough-legged hawk. PMID- 6245348 TI - [Varicella arthritis--a rare complication of varicella (author's transl)]. PMID- 6245349 TI - [Cell therapy in neoplastic disease]. PMID- 6245350 TI - [Clinical aspects and importance of human herpex simplex infections. Results of herpes antigen therapy]. AB - Herpes simplex diseases are among the most frequent sociomedical problems of our age. For the patients the recurrent diseases are particularly distressing depending on the frequency of relapse, their localization and clinical course. Immunological factors, especially cellular immune mechanisms seem to affect the frequency of relapse and particularly the clinical course of the relapse. Clinical experience so far with immunotherapy of relapsing herpes diseases with heat-inactivated herpes simplex virus antigen type 1 and type 2 are optimistic. Local painful swellings or more rarely the appearance of an urticaria have been described as side-effects within 10 years in 1 to 2% of patients. PMID- 6245351 TI - ["God's pharmacy"]. PMID- 6245353 TI - Induction of an error-prone mode of DNA repair in UV-irradiated monkey kidney cells. AB - The survival of UV-irradiated simian virus 40 (SV40) on UV-irradiated monkey kidney CV-1P cells at 33 degrees was increased over survival on unirradiated cells. During this process - called induced-virus reactivation - the progeny virus yielded by UV-irradiated cells had a much higher mutation frequency than did the progeny from unirradiated cells. Mutation rates were quantified by using phenotypic reversion towards wild-type growth of an early (tsA 58) or a late (tsB 201) temperature-sensitive SV40 mutant. Analysis of SV40 revertant genomes indicated that no detectable deletions of additions were responsible for the reversion process. These results suggest that enzymes from UV-irradiated cells are able to replicate UV-irradiated DNA by an error-prone mode of DNA repair. Induced virus reactivation and error-prone replication are probably one of the expressions of SOS functions in mammalian cells. PMID- 6245352 TI - Reactivation of herpes simplex virus in a cell line inducible for simian virus 40 synthesis. AB - The reactivation of UV-irradiated herpes simplex virus (HSV) was investigated in irradiated and unirradiated transformed hamster cells in which infectious simian virus 40 (SV40) can be induced. Reactivation was enhanced when the cells were treated with UV light or mitomycin C prior to infection with HSV. The IV dose response curve of this enhanced reactivation was strikingly similar to that found for induction of SV40 virus synthesis in cells treated under identical condictions. This is the first time that two SOS functions described in bacteria have been demonstrated in a single mammalian cell line. PMID- 6245354 TI - Facilitatory effects of 4-aminopyridine on normal neuromuscular transmission. AB - The effects of 4-aminopyridine (4-AP) on neuromuscular transmission were studied in vitro in the rat flexor digitorum longus muscles. 4-AP produced dose-dependent increases in endplate potential (EPP) amplitude, in rise time to peak, and in the average number of acetylcholine quanta released by presynaptic nerve impulses. The neuromuscular blocking effects of d-tubocurarine or low Ca2+/high Mg2+ concentrations could be completely reversed by 4-AP, and EPPs developed into muscle action potentials (APs). The drug had minimal effects on the amplitude or frequency of spontaneous miniature endplate potentials, but increased the duration of indirectly elicited muscle APs. The action of 4-AP required the presence of extracellular Ca2+; thus, its effect may be to promote Ca2+ entry into the motor nerve terminal, and thereby increase the neurally evoked transmitter release. 4-AP is effective in overcoming both presynaptic and postsynaptic blockade of neuromuscular transmission, suggesting a potential role for this drug in the treatment of neuromuscular diseases. PMID- 6245355 TI - Facilitatory effects of 4-aminopyridine on neuromuscular transmission in disease states. AB - The in vitro effects of 4-aminopyridine (4-AP) on neuromuscular transmission were determined by microelectrode techniques in intercostal muscles from patients with myasthenia gravis (MG) and the Eaton-Lambert syndrome (ELS), and in forelimb muscles from rats with experimental autoimmune myasthenia gravis (EAMG). In MG and EAMG, the amplitudes of miniature endplate potentials (MEPPs) and endplate potentials (EPPs) were reduced, and there was increased sensitivity to the blocking action of d-tubocurarine (dTc). In ELS, MEPP amplitude was normal but the average number of acetylcholine quanta released by nerve impulses was reduced, causing subthreshold EPPs. In EAMG muscle, 4-AP produced dose-dependent increases in EPP amplitude and in the duration of indirectly elicited muscle action potentials but no changes in MEPP amplitude and resting membrane potential. 4-AP completely reversed the postsynaptic blockade produced by dTc and EAMG. 4-AP appears to facilitate neuromuscular transmission in EAMG, MG, and ELS by increasing the neurally evoked transmitter release, thus overcoming either the pre- or the postsynaptic neuromuscular blockade. PMID- 6245356 TI - Glycogen cycle enzymes and cyclic nucleotides in avian muscular dystrophy. AB - Fast-frozen pectoralis muscle samples were taken from normal chickens (lines 200 and 412) and chickens having hereditary muscular dystrophy (line 304). The glycogen phosphorylase activity ratio (activity without AMP/activity with AMP) was significantly greater in dystrophic muscles (0.306 +/- 0.046) than it was in normal muscles (0.090 +/- 0.023). Glucagon treatment did not cause any changes in phosphorylase activity ratios. Isoproterenol treatment of both normal and dystrophic muscles raised the phosphorylase activity ratio of normal muscles to 0.446 +/- 0.054, which was not significantly different from that of the dystrophic muscles. The dystrophic muscles had significantly less glycogen than normal muscles (23.3 +/- 2.8 compared with 36.8 +/- 2.8 mumoles glucosyl units/g of muscle). There was no relationship of muscular dystrophy to total phosphorylase activity (measured in the presence of 1 mM AMP) and to glycogen synthase activities measured without and with glucose 6-phosphate. Normal muscles had 28% less cAMP and 49% less cGMP than dystrophic muscles, but these differences were eliminated by treatment of the chickens with glucagon. PMID- 6245357 TI - Determinants of conduction velocity in myelinated nerve fibers. AB - This article reviews the determinants of conduction velocity in myelinated nerve fibers. For fibers exhibiting geometric similarity, conduction velocity is nearly proportional to diameter. However, in classes of geometrically similar fibers, myelin thickness and internode distance are linearly related to diameter. Therefore, it is not possible to assess the relative contributions of each of these factors. The relative effects of changes in each of these parameters on conduction velocity can be assessed from studies on fibers representing different similarity classes or from theoretical parametric studies. These studies show that for a fixed axon diameter, conduction velocity increases with myelin thickness. For a fixed total fiber diameter, there is an optimal ratio of axon diameter to total fiber diameter (and therefore to myelin thickness) at which conduction velocity is maximized. Conduction velocity is dependent on internode distance, with a broad maximum centered around the value observed in normal peripheral fibers. Conduction velocity is also dependent on temperature and the properties of the axonal milieu. Thus, the conduction speed of any given fiber reflects a number of parameters and is not determined by any single structural characteristic. PMID- 6245358 TI - Peripheral neuropathy associated with disulfiram administration. AB - Very few cases of peripheral neuropathy as a complication of disulfiram therapy have been described. The clinical and electrodiagnostic features of two patients who developed a severe peripheral neuropathy during disulfiram administration are reported. Evidence is presented which suggests that disulfiram causes a dying back axonal neuropathy. PMID- 6245359 TI - Bone-marrow ablation and allogeneic marrow transplantation in acute leukemia. AB - Thirty-three patients with acute leukemia (15 with lymphoblastic leukemia and 18 with myeloblastic leukemia) were entered into a program of high-dose radiochemotherapy followed by allogeneic bone-marrow transplantation. These patients were in various clinical stages of disease. Of 10 in complete hematologic remission at the time of transplantation, seven were alive without maintenance therapy at the time of evaluation, eight to 35 months after grafting; one was in relapse. Of 11 who received transplants during partial remission, six were in remission without further treatment eight to 33 months after transplantation. In 12 the disease was refractory to chemotherapy when preparation for transplantation was started, and only one of them was alive and free of disease after 10 months. Recurrent leukemia, graft-versus-host disease, viral pneumonia, and early therapy-related toxicity were the major causes of failure. High-dose chemotherapy and total-body irradiation followed by allogeneic marrow transplantation performed during complete or partial remission can produce long-term remission of acute leukemia. PMID- 6245360 TI - Breast milk and the risk of cytomegalovirus infection. PMID- 6245361 TI - Oral retinoid treatment of human papillomavirus type 5-induced epidermodysplasia verruciformis. PMID- 6245362 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 19-1980. PMID- 6245363 TI - Hepatitis A in day-care centers. A community-wide assessment. AB - We investigated the spread of viral hepatitis in day-care centers in Maricopa County, Ariz. Over a 10-month period, 398 (40 per cent) of 1008 reported cases of hepatitis Type A or viral hepatitis of unspecified type occurred in persons closely associated with day-care centers. Outbreaks of hepatitis comprising 310 cases were identified in 30 of 308 centers in the county. In 28 outbreaks investigated, the majority of symptomatic cases occurred in household contacts or close relatives of children who attended day-care centers, with 16 per cent of the cases occurring in children who attended the centers and 15 per cent occurring in employees. Hepatitis in both employees and household contacts was strongly related to contact with children one to two years of age who attended the centers (P less than 0.001). Day-care centers appear to be important in the spread of hepatitis A in the United States. PMID- 6245364 TI - Diffuse polyclonal B-cell lymphoma during primary infection with Epstein-Barr virus. PMID- 6245365 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 22-1980. PMID- 6245366 TI - Epstein-Barr virus--oncogen or mitogen? PMID- 6245367 TI - Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. AB - In near-physiological concentrations, glucocorticoid hormones cause the death of several types of normal and neoplastic lymphoid cell, but the mechanisms involved are unknown. One of the earliest structural changes in the dying cell is widespread chromatin condensation, of the type characteristic of apoptosis, the mode of death frequently observed where cell deletion seems to be 'programmed'. It is shown here that this morphological change is closely associated with excision of nucleosome chains from nuclear chromatin, apparently through activation of an intracellular, but non-lysosomal, endonuclease. PMID- 6245368 TI - A site for the potentiation of GABA-mediated responses by benzodiazepines. AB - The benzodiazepines have been well characterised as minor tranquillizers and attempts to explain their unique spectrum of activity have included suggestions that they may interact with a variety of neurotransmitter systems. Recently, a possible interaction with the gamma-aminobutyric acid (GABA) system has received most attention. Benzodiazepines potentiate the actions of both synaptically released and exogenously administered GABA on mammalian neuronal preparations but the site of action within the GABA response mechanism has not been determined. Binding studies suggest that benzodiazepines combine with highly specific sites in the neuronal membrane and that these sites have some indirect association with GABA receptors. To investigate this association further in a functioning GABA system, quantitative studies have been made in vitro on neuronal depolarisations mediated by GABA receptor activation. Evidence has already been presented that bicuculline is most probably a competitive antagonist at the GABA receptor while picrotoxin acts as an antagonist at a separate site. Here flurazepam is shown to attenuate preferentially the action of picrotoxin rather than bicuculline and a model is suggested for the site of action of these drugs within the GABA response mechanism. PMID- 6245369 TI - Selfish genes, the phenotype paradigm and genome evolution. AB - Natural selection operating within genomes will inevitably result in the appearance of DNAs with no phenotypic expression whose only 'function' is survival within genomes. Prokaryotic transposable elements and eukaryotic middle repetitive sequences can be seen as such DNA's and thus no phenotypic or evolutionary function need be assigned to them. PMID- 6245370 TI - In vitro effects of high molecular weight forms of ACTH on the fetal sheep adrenal. AB - The direct involvement of the pituitary-adrenal axis in birth has been well established, at least in sheep, and its removal prolongs pregnancy. As part of the process the fetal sheep adrenal grows rapidly during the 10-15 d prepartum and is associated with a large rise in the plasma corticosteroid concentration. This does not seem to result from an increased ACTH secretion. The fetal adrenal in vivo seems refractory to circulating ACTH and shows poor response to elevation of plasma concentration. Thus the signal for the adrenal hypertrophy and the initiation of parturition remains unclear. The responsiveness of the fetal adrenal to ACTH has been re-examined using isolated adrenal cells. The study shows that in the fetal sheep these are not inherently unresponsive to ACTH, but that high-molecular-weight forms of ACTH block the action of ACTH. These peptides may be responsible for controlling the activity of the adrenal in situ. PMID- 6245371 TI - Retinoids specifically enhance the number of epidermal growth factor receptors. AB - Retinoids elicit many biological and biochemical responses from cells in vitro. One widely used criterion for the responsiveness of cells to retinoids is inhibition of growth; retinoids reduce the saturation density and/or growth rate of many normal and tumorigenic cell lines. Propagation of eukaryotic cells has been demonstrated to be dependent on the presence of macromolecular growth factors such as epidermal growth factor (EGF), which can stimulate proliferation of epithelial and fibroblastic cell lines. We now describe the effect of retinoids on the binding of EGF to its receptor. Retinoic acid enhances binding of 125I-labelled EGF to various fibroblastic and epidermal cell lines. It has no marked effect on the affinity of this growth factor for its receptor, but increases the number of EGF receptor sites. Retinoic acid has little effect on the binding of concanavalin A (Con A) and insulin, indicating the specific nature of the action of retinoids on cell-surface glycoproteins. Treatment of cells with the phorbol ester 12-o-tetradecanoyl phorbol-13-acetate (TPA) and retinoic acid shows poor antagonism between these compounds on EGF binding. It has been previously shown that retinoids induce or stimulate differentiation of embryonal carcinoma cells. EGF binding can be used as a marker to monitor differentiation of these cells. PMID- 6245372 TI - Vasopressin increases water permeability in inducing pores. PMID- 6245373 TI - A novel alpha-globin gene arrangement in man. AB - The human genome has two linked alpha-globin genes on chromosome 16. Deletion of one or more of them, as occurs in alpha-thalassaemia, leads to a reduced output of alpha-globin mRNA in proportion to the number of alpha-globin genes lost. In some racial groups deletion of one of the pair of alpha-globin genes may result from unequal crossing over between the genes on homologous chromosomes by a mechanism resembling that postulated for the formation of the delta beta fusion genes of the Lepore haemoglobins. By analogy, the opposite chromosome in this cross-over should have three alpha-globin genes just as the 'anti-Lepore chromosome has three non-alpha chain genes. We describe here a Welsh family in which three members have five alpha-globn increased alpha mRNA output and it may therefore produce the phenotype of mild beta-thalassaemia. PMID- 6245374 TI - E. coli RNA polymerase promoters on superhelical SV40 DNA are highly selective targets for chemical modification. PMID- 6245375 TI - Tetanus toxin blocks the neuromuscular transmission in vitro like botulinum A toxin. PMID- 6245376 TI - Pharmacological characterization of central alpha-adrenoceptors which mediate clonidine-induced locomotor hypoactivity in the developing rat. AB - The present experiment was designed to pharmacologically characterize receptors which mediate the clonidine-induced locomotor change in the developing rat. A subcutaneous injection of clonidine (0.78 mumol/kg) produced locomotor hyperactivity in 7-day-old rats but hypoactivity in 20-day-old rats. Phenoxybenzamine (1.5 mumol/kg, 5.9 mumol/kg and 15 mumol/kg) decreased spontaneous activity in a dose-dependent manner but did not antagonize clonidine induced hypoactivity in 20-day-old rats. By contrast, the significant reversal of the clonidine-induced hypoactivity by pretreatment with phentolamine (1.6 mumol/kg and 6.3 mumol/kg), yohimbine (1.3 mumol/kg and 5.1 mumol/kg) and piperoxan (7.4 mumol/kg) was observed at such doses when the blockers did not cause any hypoactivity by themselves. It is suggested that clonidine could induce locomotor hypoactivity by activating presynaptic (alpha 2-type) alpha adrenoceptors in the CNS of 20-day-old rat. PMID- 6245378 TI - [Reactions of neurons of the reticular and ventral anterior thalamic nuclei to electrical stimulation of the centrum medianum of the thalamus]. AB - Responses of 145 reticular (R) and 158 ventral anterior (VA) thalamic neurons to electrical stimulation of centrum medianum (CM) were studied in cats anaesthetized with thiopental sodium (30-40 mg/kg intraperitoneally) and immobilized with d-tubocurarine (1 mg/kg). 4.1% of R and 4.4% of VA neurons under study responded to CM stimulation by antidromic spike (latency 0.3-2.0 ms). The conduction velocity of antidromic excitation in axons of those neurons was found to be 1.7-7.6 m/s. There were neurons which responded by antidromic spike to the other thalamic nuclei stimulation as well as to CM. This fact is the electrophysiological proof of the axonal branching in these neurons. 53.8% of R and 46.9% of VA neurons responded to CM stimulation with orthodromic excitation. Two groups of cells were separated among neurons excited orthodromically. The first group neurons responded to CM stimulation by discharges composed of 6-12 spikes with frequency of 130-640 per second. The neurons of the second group generated a single spike. Inhibitory reactions were noticed only in 0.7% of R and in 4.4% of VA neurons. It is shown that afferent impulses from relay nuclei, lateral posterior nucleus and motor cortex converged to some R and VA neurons responding to CM. PMID- 6245377 TI - Inhibitory effects of mepacrine and eicosatetraynoic acid on cyclic GMP elevations caused by calcium and hormonal factors in rat ductus deferens. PMID- 6245379 TI - [Monosynaptic excitation of motor neurons of the nucleus of the accessory nerve by reticulofugal impulses]. AB - Responses of accessory motoneurons to electrical stimulation of the ipsilateral nucleus gigantocellularis of medullary reticular formation were recorded intracellularly in cats under chloraloze-nembutal anesthesia. The stimulation evoked in the accessory motoneurons monosynaptic EPSPs with latency from 0.6 to 1.0 ms, maximal amplitude 4.0 mV and duration 10 ms. Weak facilitation of EPSPs and absence of action potentials were demonstrated using paired shocks and rhythmic stimulation of the nucleus. PMID- 6245380 TI - Embryonic carcinosarcoma (mixed tumour) of the pineal gland. AB - The present paper reports on a pineal gland tumour in an 8-year-old male child. Microscopic examination revealed a carcinomatous and a sarcomatous component. The aspect was characteristic of mixed embryonic carcino-sarcoma described in germ cell layer tumours of the gonads and kidney (Wilms' tumour). Ultrastructurally, the mixed character of the tumour was confirmed and also more differentiated elements were found differing from the appearances described in germ cell layer tumours. On the basis of the morphological examination it is concluded that at least in a proportion of the malignant mixed tumours of the pineal gland, their origin is to be found in the local neural elements and not the extraneural ones. PMID- 6245381 TI - Synaptosomal uptake: the modifying effect of mitochondria. PMID- 6245382 TI - Isolation of rat brain subcellular fraction enriched in putative neurotransmitter receptors and synaptic junctions. AB - A simple reliable method was developed for the rapid isolation of a synaptic plasma membrane-enriched fraction from rat brain. The procedure involves the direct lysis of a crude mitochondrial fraction followed by a combined flotation sedimentation density gradient centrifugation in a fixed-angle centrifuge rotor. All fractions have been characterized with respect to relative enrichment of (Na+ K+)ATPase activity as well as putative cholinergic neurotransmitter receptors determined by [125I]alpha-bungarotoxin and [3H]quinuclidinyl benzilate binding. The 2- to 4-fold relative enrichment of putative receptor binding sites correlated well with the 4-fold enrichment of morphologically identifiable synaptic junctions in the synaptic plasma membrane enriched fraction. PMID- 6245383 TI - Absence of triphosphoinositide in the chloroform-methanol extract of cerebral cortex containing the cholinergic proteolipid. PMID- 6245384 TI - Pituitary-adrenal function in pseudopregnant rats. AB - Pseudopregnancy inhibited plasma corticosterone response to stress. The production of corticosterone by adrenal slices in vitro was also discussed; no changes in adrenal 5 alpha-reductase activity were observed. Secretion of corticosterone in the adrenal venous blood was decreased as well, without changes in dehydrocorticosterone or tetrahydrocorticosterone secretion rates. Treatment with ACTH increased the secretion rates of corticosterone to the range observed in control rats. Steady state secretion and metabolism of corticosterone was unchanged. The data indicate that the diminished responses in plasma concentrations, in vitro production, and secretion rates of corticosterone obtained in pseudopregnant rats after stress, are secondary to changes on the release of ACTH from the pituitary gland rather than to adrenal steroid secretion per se or handling of corticosterone by the liver. The expected rise in plasma prolactin observed in cycling rats after stress was absent in pseudopregnant rats. The data suggest that an inhibition of the prolactin release mechanisms similar to that observed with the release of ACTH may have occurred after stress. The dynamics involved in the changes affecting the release of pituitary hormones in pseudopregnant rats are still unclear. PMID- 6245385 TI - Involvement of vasopressin in corticotropin-releasing effect of hypothalamic median eminence extract. AB - Incubation of anterior pituitary (AP) fragments of rats was used to determine the specific role played by vasopressin (VP) in the overall effect of crude hypothalamic median eminence (HME) extract on ACTH release. Using the property of an AVP antiserum (AS) to completely abolish the CRF-like effect of hypothalamic VP without apparently affecting the effect of CRF, we show that under specific incubation conditions, the effect of the two secretagogues are additive at the pituitary level. ACTH secretion of pituitaries was enhanced when incubation was carried out in the presence of VP together with a maximum effective dose of VP free HME extract (from Brattleboro rats). These observations favor the hypothesis that VP and CRF have different receptor sites in the anterior pituitary. PMID- 6245386 TI - Lhermitte-Duclos disease: case report with computerized tomographic scan. AB - Lhermitte-Duclos disease is a rare, benign cerebellar condition that mimics a posterior fossa mass and has never been diagnosed preoperatively. Grossly, the diseased cerebellar tissue is tough and poorly demarcated; microscopically, the cortex has a thick outer layer of nerve fibers, an inner layer of abnormal ganglion cells, and the absence of normal Purkinje cells. The prognosis, based on cases treated surgically since 1955, is good. A case is reported in which cranial computerized tomography performed 5 years after the partial removal of abnormal tissue showed neither enhancement nor radiolucency. PMID- 6245387 TI - Amebic abscess of the brain. AB - Brain abscesses caused by Entamoeba histolytica were treated in two residents of New Jersey, neither of whom had traveled beyond the eastern United States. The diagnosis in Case 1 was confirmed by the presence of ameba in both brain and pituitary abscesses. An elevated indirect hemagglutination (IHA) titer of 1:4096 and response to specific treatment with metronidazole and chloroquin were the criteria for diagnosis in Case 2. The computerized tomographic appearance of an amebic abscess is that of a rapidly progressive lesion without reaction in the adjacent brain. Of the seven reported cures, all of the patients received appropriate chemotherapy. Five of the seven were operated upon. PMID- 6245388 TI - Principles of the new World Health Organization (WHO) classification of brain tumors. PMID- 6245389 TI - Olivary hypertrophy: histochemical demonstration of hydrolytic enzymes. AB - Of four patients with palatal myoclonus, three had infarcts resulting from atherosclerosis, and one had cerebral emboli from a left atrial myxoma. Three specimens showed lesions in the brainstem and bilateral hypertrophy of the inferior olivary nuclei; the fourth revealed unilateral olivary changes caused by an infarct in the contralateral dentate nucleus. After incubation for acetylcholinesterase, neuropilar and capillary wall staining were absent or much reduced, but there was increased denisty of reaction product in the neuronal cell bodies and in numerous tortuous dendrites. Methods for acid phosphatase showed strong activity in the dendrites and glomeruloid structures of the diseased olives. Reactions for nonspecific esterase indicated dendritic expansion and reduced staining density in nerve cell bodies, but augmented glial reactivity. PMID- 6245390 TI - Search for cytomegalovirus and herpes simplex virus genetic information in multiple sclerosis. AB - Human cytomegalovirus and herpes simplex virus DNA probes were labeled in vitro and hybridized to the DNA extracted from brains of patients with multiple sclerosis (MS) to detect the presence of genetic information related to these viruses. We were unable to detect any virus-related genetic information complementary to these probes. These results indicate that the two viruses are not involved in MS, or else the genetic information, if present, is below the sensitivity of detection of this hybridization technique. PMID- 6245391 TI - Eaton-Lambert syndrome: case report. PMID- 6245392 TI - [Therapy of myasthenia gravis in pregnancy]. PMID- 6245393 TI - [Myoblastic sarcomas of the female genital system. Description of 3 cases with vaginal localization and 2 cases with uterine localization]. PMID- 6245394 TI - Noncondylomatous cervical wart virus infection. AB - Human papillomavirus (HPV) infections of the genital tract frequently involve cervical epithelium and produce a macroscopically flat lesion that the authors have called noncondylomatous cervical wart virus infection (NCWVI). Over a 6 month period, 92 of 7281 routine cervical smears (1.3%) and 46 of 183 colposcopically directed punch biopsies (25%) showed morphologic evidence of wart virus infection. The etiologic role of HPV was confirmed by the demonstration of virus particles in 24 of 53 cases (45%) examined by electron microscopy. The colposcopic features of NCWVI consist principally of epithelial opacity and vascular atypia, leading to frequent confusion with cervical intraepithelial neoplasia. Differences in surface contour, color, vascular patterns, and topography generally permit colposcopic differentiation. These 2 conditions sometimes coexist; whether the association is causal or casual in not presently known. PMID- 6245395 TI - Treatment of metastatic trophoblastic disease with poor prognosis. AB - Fifty-one patients are presented who were treated for poor-prognosis gestational trophoblastic disease by physicians at Duke University Medical Center (Southeastern Regional Trophoblastic Disease Center) between 1968 and 1978. Disease in 72% (37 of 51 patients) is currently in remission (8 months to 10 years). Treatment was primarily by multiagent chemotherapy, with adjunctive surgery and radiation therapy in selected patients. Unsuccessful chemotherapy prior to treatment at this center, a prolonged interval from the antecedent pregnancy to treatment, and liver metastases portended a worse prognosis in these patients. PMID- 6245396 TI - Giardiasis in protein calorie malnutrition at Gadjah Mada Hospital, Yogyakarta. PMID- 6245397 TI - Rickets: a roentgenographic scheme for diagnosis. PMID- 6245398 TI - Ultrasonography in primary hepatic tumors in early childhood. AB - Ultrasonography was useful in preoperative investigation of primary hepatic tumors in nine children, aged 4 weeks to 4 years. In all patients, the hepatic origin and the solid or mixed echogenic nature of the tumor was determined. In two children (one with hemangioendothelioma, one with cystic mesenchymoma) the ultrasonographic findings were even more specific when correlated with angiography and/or histology. Ultrasonography in children with hepatomegaly should be performed as a screening procedure before angiography, to determine if enlargement of the liver is of tumorous origin. For follow-up, ultrasonography should be preferred over radionuclide imaging because it does not require the use of ionizing energy. PMID- 6245399 TI - Computed tomography and ultrasound of renal and perirenal diseases in infants and children. Relationship to excretory urography in renal cystic disease, trauma and neoplasm. AB - Forty-seven infants and children had excretory urography, ultrasound, and computed tomography with the renal and perirenal areas as the primary regions of interest. Ultrasound is an excellent screening procedure and is often diagnostic especially in renal cystic disease. Computed tomography best demonstrated the extent of renal injury and best delineated the geography, character, and extent of solid renal and perirenal neoplasms (screened by ultrasound). Excretory urography in these patients was at times incorrect, often underestimated the extent of the pathologic process, and is often unnecessary. PMID- 6245400 TI - An after-hours pediatric walk-in clinic for an entire urban community: utilization and effectiveness of follow-up care. AB - A retrospective record review was used to examine utilization of a pediatric walk in clinic available to an entire urban community and to evaluate the effectiveness of follow-up care for a sample of the users of this facility who receive their regular pediatric care at a local comprehensive child health center. Results indicate that this walk-in facility is used extensively for the care of nonemergency conditions. The findings did not, however, support the generally accepted belief that a disproportionate number of Medicaid-supported and minority children overuse emergency type facilities. Utilization did not differ by race or medical care financing. Only 35.6% of the children who were advised to make a follow-up visit to the health center actually did so. White children complied significantly more often than black children (48.0% vs 15.8%). A larger percentage of patients for whom follow-up was optional (48.5%) than for whom follow-up was recommended (35.6%) made a return visit. Noncompliance with recommendations concerning follow-up care of adult users of emergency type facilities is a well recognized problem; the present study demonstrates a similar problem among children. PMID- 6245401 TI - [Role of rotavirus in gastroenteritis in infants at the University Hospital Center of Grenoble. Value of serology]. PMID- 6245402 TI - Effects of neonatal administration of clomiphene citrate on sexual behavior of female rats: a preliminary report. AB - Female rats were treated with the nonsteroidal estrogen antagonist clomiphene citrate for the first 5 days postpartum. The expectation was that clomiphene would influence the sexual development of these animals as is the case with sexually immature animals treated with steroidal compounds. Analysis showed that treatment with clomiphene completely disrupted the adult sexual behavior of the female. In five consecutive days of testing the experimental females were never observed to mate. They were mounted significantly less often than controls, suggesting that the males were less attracted to them than to normal females. The initial suggestion that clomiphene might affect the sexual behavior of females has been supported; however, further research must be done to identify the underlying mechanism of the change. PMID- 6245403 TI - Do isolated membranes and purified vesicles pump sodium? A critical review and reinterpretation. PMID- 6245404 TI - [Portal hypertension in sarcoidosis. Three cases including one with liver fibrosis and malignant hepatoma with osseous stroma (author's transl)]. AB - The high incidence of hepatic lesions in sarcoidosis contrasts with the extreme rarity of portal hypertension. The mechanism of the latter is as obscure as the pathogeny of the disease. The liver may contain many or very few tuberculoid follicles, and its structure may be normal and non-fibrotic (as in our first two patients) or sclerotic, though rarely cirrhotic. In most cases the spleen is enormous, which raises the problem of portal hypertension by overload. Our third patient seems to be an unique case of progressive change to malignant hepatoma with osseous metaplasia, complicated with cervical metastases. PMID- 6245406 TI - [Case of esophageal hiatal hernia diagnosed initially as lung carcinoma]. PMID- 6245407 TI - [The correlation between lymphographic findings and microscopic examination of retroperitoneal lymph nodes in patients with embryogenic testicular tumors other than pure seminomas]. PMID- 6245405 TI - [Survival of Entamoeba histolytica in pus from a liver abscess]. PMID- 6245408 TI - [Cytoenzymatic and immunological tests in workers exposed to industrial noise]. PMID- 6245409 TI - [Selected chapters from clinical bacteriology. Herpesviruses]. PMID- 6245410 TI - [Treatment of the instabilities of the knee joint (author's transl)]. PMID- 6245411 TI - [Principle of creating complex blood substitutes for the treatment of the terminal phase of shock]. PMID- 6245412 TI - [Adrenocorticotropic activity of the anterior lobe of the hypophysis and the course of pulmonary tuberculosis in diabetes mellitus]. PMID- 6245413 TI - Zinc and dietary fibre: observations on a group of vegetarian adolescents. PMID- 6245414 TI - Exercise and wheat bran: effect on whole-gut transit. PMID- 6245415 TI - Dietary fibre and blood pressure. PMID- 6245416 TI - Host animal--rumen relationships. PMID- 6245417 TI - Extraction of collagenase of possible leucocyte origin from ulcerating corneas of vitamin A deficient rats. PMID- 6245418 TI - Perinatal or adult exposure to cannabinoids alters male reproductive functions in mice. PMID- 6245419 TI - Schedule-dependent tolerance to behavioral effects of delta 9 tetrahydrocannabinol when reinforcement frequencies are matched. AB - Squirrel monkeys pressed a lever under a multiple interresponse-time greater than 28-sec, modified random-interval schedule which provided comparable frequencies and temporal distributions of food pellet presentation in the two components. Daily intramuscular administration of either 0.25 or 1.00 mg/kg delta 9 tetrahydrocannabinol resulted initially in suppression and/or disruption of responding and concomitant decreases in the frequency of food presentation in both components. Responding in both components next increased, resulting in recovery of baseline frequencies of pellet delivery during the random-interval component, but continued depression during the interresponse-time schedule. The drug-induced changes in responding under the interresponse-time schedule diminished with repeated injections, whereas response rates during the random interval schedule sometimes remained elevated. Interresponse-time distributions under the interresponse-time schedule showed that with repeated administration of the drug only those characteristics which had the greatest effect on reinforcement frequency recovered to baseline levels. When drug injections were replaced by daily injections of the vehicle, responding was greatly disrupted only during the random-interval component. These findings are only partially consistent with other results which suggest aht tolerance development to the behavioral effects of delta 9-tetrahydrocannabinol is greatly enhanced if the drug initially produces reinforcement loss. PMID- 6245420 TI - Malignant transformation in concurrent benign mixed tumors of the parotid and submaxillary glands. AB - This patient is the only reported case of concomitant mixed tumors of the parotid and contralateral submaxillary gland. Each lesion had histologic changes consistent with different stages in the transformation of a benign to a malignant mixed tumor. Identifying premalignant disease in the parotid tumor and early preinvasive carcinoma in the submaxillary tumor lends support to the concept of malignant progression in salivary gland mixed tumors. PMID- 6245421 TI - Paget's disease of the breast after subcutaneous mastectomy and reconstruction with a silicone prosthesis. AB - Eight years after subcutaneous mastectomy for extensive fibrocystic disease, a patient developed Paget's disease of the breast associated with an underlying infiltrating duct cell adenocarcinoma. We emphasize the need for meticulous examination of the subcutaneous mastectomy specimen and long-term follow-up examination of the breasts in patients treated with subcutaneous mastectomy. PMID- 6245423 TI - Effects of pentazocine and other opiates on shock detection in the rat: involvement of opiate and dopamine receptors. AB - The hypothesis that the antinociceptive effects of pentazocine, a mixed agonist antagonist opiate of the benzomorphan class, are mediated by a dual opiate dopaminergic mechanism was tested using a two-choice procedure in which rats were required to discriminate the presence or absence of shock. The results showed that pentazocine decreased shock sensitivity and speed of responding, effects that were qualitatively similar to those of morphine. However, while the antinociceptive effect of both pentazocine and morphine could be antagonized by opiate receptor blockage, that of pentazocine, but not of morphine, could also be antagonized by dopamine receptor blockade. Observations with levorphanol and phenazocine suggested further that dopamine, as well as opiate receptor agonism may be characteristic of the benzomorphans. PMID- 6245422 TI - Head-twitch response induced by tyramine. AB - The intracerebroventricular (IC) administration of tyramine (TyA) induced a characteristic head-twitch response in mice pretreated with safrazine, a monoamine oxidase inhibitor. Safrazine-pretreated mice exhibited similar head twitches following the IC treatment of serotonin (5-HT). The maximum dose of 5-HT which did not elicit head-twitches significantly potentiated TyA-induced head twitches. Antiserotonergic drugs such as morphine and dimethothiazine antagonized TyA-induced head-twitches. A serotonergic denervator, 5,6-dihydroxytryptamine, potentiated head-twitch induced by TyA or 5-HT. Both TyA-induced and 5-HT-induced head-twitches were inhibited by dopamine and noradrenaline, while catecholaminergic denervators such as reserpine and 6-hydroxydopamine, and diethyldithiocarbamic acid, a dopamine-beta-hydroxylase inhibitor, increased the TyA response. These results indicate that head-twitches induced by TyA may be mediated via the serotonergic system and may inhibit the catecholaminergic system. PMID- 6245424 TI - Behavioral and biochemical effects of chronic delta 9-tetrahydrocannabinol in rats. PMID- 6245425 TI - Survival of bone marrow-engrafted mice subsequent to protection from lethal radiation by WR 2721. PMID- 6245426 TI - Subcellular localization and paramagnetic properties of signals observed in Krebs II ascites cells by electron spin resonance spectroscopy. PMID- 6245427 TI - False aneurysm formation following arteriographic intimal dissection: serial studies in 2 patients. AB - Two patients with metastatic islet-cell carcinoma underwent multiple hepatic artery catheterizations for streptozotocin infusion. An intimal flap was raised during one of the initial arteriographic procedures and a false aneurysm developed. The progression of the aneurysm was documented on sequential studies. False aneurysm formation appears to be a relatively unappreciated complication of intimal dissection, and these 2 cases permitted observation of their natural history. PMID- 6245428 TI - Ultrasonic features and radionuclide correlation in liver cell adenoma and focal nodular hyperlasia. AB - Ultrasonic features of three cases of liver cell adenoma (LCA) and two cases of focal nodular hyperplasia (FNH) are presented. These tumors have similar sonographic appearances presenting either as solid masses or containing sonolucent areas due to hemorrhage or necrosis. Although these ultrasonic features in patients with an area of decreased activity on 99mTc-sulfur colloid (Tc-SC) liver scans are not specific for LCA or FNH, such findings in the appropriate clinical setting are suggestive of these lesions. The combination of a solid mass on ultrasonography and a normal Tc-SC radioisotope liver study may be relatively specific for uncomplicated FNH. PMID- 6245429 TI - The use of ultrasound in the evaluation of trophoblastic disease and its response to therapy. AB - Thirty-nine patients with trophoblastic disease were studied to determine the usefulness of ultrasound in identifying risk patterns and response to therapy. Serial measurements of serum human chorionic gonadotropin-beta subunit (HCG-BSU) were compared with ultrasonographic uterine and theca lutein cyst volumes. In 16 patients ultrasound demonstrated theca lutein cysts, many of which were not palpable on physical examination. Although there was a significant decrease in uterine volume and a change in the sonographic pattern following evacuation, volume slowly returned to normal over a period of several months. Persistent trophoblastic disease was more accurately detected by HCG-BSU measurements than by ultrasound. Persistent disease developed in 44% of those patients who had theca lutein cysts and in 22% of those without cysts. Patients with theca lutein cysts did not consistently have higher HCG-BSU levels than patients without cysts, and it is concluded that ultrasound is the best method for detecting these cysts. PMID- 6245430 TI - Proton imaging for medical applications. AB - In order to demonstrate the potential advantages of proton imaging for medical use, a 205-MeV proton beam was developed using the Argonne National Laboratory Booster I synchrotron. Data were taken using a narrow scanning beam and an electronic detector system. The dose reduction and an improved mass resulution over the radiographs. The images also show significant differences in the proton stopping power of different tissues, thus demonstrating considerable potential in soft-tissue imaging. The development of a proton tomographic scan system is also briefly discussed. PMID- 6245431 TI - [Goodpasture's syndrome: 2 new cases. Possible role of some substances in its development]. PMID- 6245432 TI - [A case of hepatocarcinoma with multiple osseous metastases]. PMID- 6245433 TI - Human breast cancer in nude mice: a model for testing endocrine treatment. PMID- 6245434 TI - A hormone-dependent human breast cancer cell line grown in defined medium. PMID- 6245435 TI - The role of substantia gelatinosa as a gate control. AB - A gate control exists by which peripheral afferents and descending pathways can modulate sensory transmission. Evidence is presented that the mechanism may exist in the substantia gelatinosa laminae II and III. This area receives all known types of peripheral afferent from skin, from viscera and from high-threshold muscle afferents. The chemistry of the region is unique. Peripheral afferent terminals contain substance P, somatostatin, and fluoride-resistant acid phosphatase. Cells in the region contain enkephalin and GABA. At least three descending systems from the brainstem terminate in the area. The anatomical substrate exists by which cells in laminae II and III can receive afferents and descending axons and intrude onto cells of laminae I, IV, and V. Stimuli limited to the axons of laminae II and III cells in the Lissauer tract produce dorsal root potential and change the excitability of mono- and polysynaptic reflexes. They also change the excitability and receptive fields of cells in laminae IV and V. Recording from single units in laminae II and III reveals cells with many unusual properties not seen in the large dorsal horn cells. These unusual properties include small receptive fields, very prolonged responses to single stimuli, prolonged habituation, and shifting receptive fields. The action of the gate control shows it to be subtle and far beyond a simple control of overall excitability. Excitations and inhibitions are independently controlled. Different types of convergent afferent may be turned on and off. There are signs of both short-and long-lasting actions. It seems that a good case has been made for the cells of substantia gelatinosa taking part in the gate control mechanism. PMID- 6245436 TI - Cyclic AMP and the pathogenesis of myocardial injury. AB - Rabbits were given N6, O2, dibutyryl 3', 5' - cyclic AMP DB-cAMP), 2.5 micrograms/kg/min, i.v. for 90 min. to determine if activation of the cyclic neucleotide system is a potential cause of myocardial injury. They were sacrificed 7 or 14 days after infusion and the hearts examined by light and electron microscopy. Cardiac lesions were uniformly present in all hearts. They were primarily those of myofribrillar degeneration and characterized by hypercontracted muscle fibers with transverse band formation, but no inflammatory response. Additional ultrastructural alterations included foci of myofiber lysis, mitochondrial translocation, and deep scalloping of sarcolemma. The SR and T system showed varying degrees of dilatation. These changes were equally intense 2 weeks after giving DB-cAMP. Similar findings have been reported in catecholamine cardiomyopathy and numerous pathological states. It is suggested that excessive stimulation of the cyclase system can serve as a common mechanism in the pathogensis of myocardial damage by a broad spectrum stimuli. PMID- 6245438 TI - Cyclic AMP-dependent protein kinases in the rat myocardial cytosol. AB - The optimal assay conditions for rat myocardial cytosol protein kinases have been determined. The assay medium contained in 0.25 ml: 40 mM Tris/HCl pH 7.4, 5 mM MgCl2, 600 micrograms histone f1, 10--30 micrograms enzyme protein, 32 microM [gamma-32P]-ATP, with or without additions of 1 microM cAMP. The incubation time at 37 degrees C was 5 minutes. The protein kinase activity in the absence of cAMP decreased with development, while the activity in the presence of cAMP remained unchanged. The protein kinase activity of the left ventricle was higher than that in the right ventricle. PMID- 6245437 TI - Erythrocyte nucleotides from control and lead-treated rabbits. AB - Significant abnormal elevations of the erythrocyte pyrimidine nucleotides UTP and CTP were observed in rabbits after 60 days of oral exposure to lead acetate at a dose of 30 mg/kg/day. No significant changes in purine nucleotides were observed. The increased erythrocyte pyrimidine nucleotides were accompanied by a decrease in red cell pyrimidine 5'-nucleotidase (P5N) activity, an increase in zinc erythrocyte protoporphyrin concentration, and elevated whole blood lead levels. Quantitative measurement of the major 5'-nucleotides in rabbit red cells was achieved by high performance liquid chromatography. The accumulation of UTP and CTP as the results of chronic lead exposure may be explained on the basis of inhibited P5N coupled with the presence of an active nucleoside diphosphokinase. PMID- 6245439 TI - Identification of 1,5-anhydroglucitol in thin-layer chromatograms. AB - The chromatographical characteristics of 1,5-anhydroglucitol in thin-layer chromatograms can be studied using the customary carbohydrate solvents. Both hydrogen peroxide and sodium metaperiodate oxidation reactions were tested in order to find a specific colour reaction for the detection of the compound. 1,5 anhydroglucitol was readily converted by periodate into an intermediate product which produced an intense orange-red colour with diphenylamine aniline reagent. According to data obtained from periodate oxidation, IR spectroscopy and mass fragmentography, the intermediate product was a dialdehyde compound with a C6 structure, possibly formed through cleavage at C2-C3. The formation of a compound of this kind without chain cleavage in the periodate oxidation of C6 carbohydrates is uncommon. Periodate oxidation followed by diphenylamine-aniline reaction affords a sensitive and specific method for the detection of 1,5 anhydroglucitol. PMID- 6245440 TI - Entero-oxyntin: a stimulant of gastric acid secretion extracted from porcine intestine. AB - A peptide that further augments gastric acid secretion in cats, maximally stimulated by pentagastrin, was identified in porcine upper small intestine. Since the peptide stimulated basal and maximally pentagastrin-stimulated acid secretion to the same extent, it appears to act on a receptor different from the gastrin receptor and thus may be designated entero-oxyntin, a mediator of the intestinal phase of acid secretion. PMID- 6245441 TI - The role of acute hepatitis type A, B, and non-A non-B in the development of chronic active liver disease. AB - In 19 patients followed from biopsy-verified acute viral hepatitis to chronic active liver disease and 74 patients followed to complete resolution verified by a normal liver biopsy, sera from the acute phase were studied for serologic evidence of hepatitis type A and B. Eleven of the 19 patients who developed chronic active liver disease progressed from acute hepatitis type B and 7 from acute hepatitis type non-A non-B. One patient could not be classified because the sera were exhausted. None had serological markers of actual hepatitis type A infection. Of the 74 patients with a histologically complete resolution, the acute episode could be classified as type B hepatitis in 47 and type A hepatitis in 13 patients. The remaining 14 patients were classified as having acute viral hepatitis type non-A non-B. Our findings confirm that type B and non-A non-B hepatitis may give rise to chronic liver disease, whereas type A hepatitis so far has not been demonstrated to initiate a chronic liver disease. PMID- 6245442 TI - Circulating immune complexes and complement-fixing antibodies in patients with varicella-zoster infection. Relationship to debut of the disease. AB - Serum samples from 32 varicella-zoster (VZ)-infected patients were examined for circulating immune complexes (IC) within 1 1/2 week after debut of the skin rash as well as during the following 5 weeks. Three test systems were used: a complement consumption (CC) assay, a C1q solid phase (CU1-SP) assay and a polyclonal rheumatoid factor-binding (pRF-I) assay. The CC and pRF-I assays were the most effective in detecting large IgG aggregates of IC, while aggregates of intermediate and small size were more easily demonstrated in the C1q-SP assay. IC were demonstrated in at least 2 assays simultaneously in 16 patients. Four of these patients were IC-positive in both observation periods, while 11 converted to IC-positive in the second observation interval. In 3 patients circulating IC were demonstrable as late as 8--10 weeks after the appearance of the skin rash. Maximal levels of complement-fixing antibodies to VZ antigens were observed 2 to 5 weeks after the appearance of the rash. PMID- 6245443 TI - Psychosocial treatment of schizophrenia, or psychosocial help for people with schizophrenia? PMID- 6245444 TI - [Use of an enzymatic immune method (ELISA) for the serodiagnosis of amebiasis]. AB - The Enzyme Linked Immunosorbent Assay (ELISA) was compared with the indirect immunofluorescence antibody test (IFAT) and with the counter immunoelectrophoresis (CIE) in the serology of amebiasis. In cases of liver abscesses, the ELISA was as sensitive as CIE, but slightly more sensitive than IFAT. In cases where the patient asymptomatically passed cysts of E. histolytica, none of the three tests was positive. As a routine laboratory screening test, the ELISA proved to be the most convenient of the three. PMID- 6245445 TI - Glutamine- and N-acetylglutamate-dependent carbamoyl phosphate synthetase in elasmobranchs. AB - High levels of glutamine- and N-acetyl-L-glutamate-dependent carbamoyl phosphate synthetase activity are present in liver extracts of marine species of fish that retain high levels of urea in their tissues for the purpose of osmoregulation. The function of the synthetase in these species appears to be related to urea synthesis. PMID- 6245446 TI - Tumor-promoting phorbol esters stimulate hematopoietic colony formation in vitro. AB - Tumor-promoting phorbol esters stimulated mouse bone marrow cells to form myeloid colonies in agar cultures without added colony-stimulating factors. The colony stimulating ability of various phorbol esters correlated well with their ability to promote skin tumors in vivo. These results suggest that phorbol esters mimic the action of specific colony-stimulating factors that regulate growth. PMID- 6245447 TI - Widespread occurrence in frogs and toads of skin compounds interacting with the ouabain site of Na+, K+-ATPase. AB - Amphibians of the family Bufonidae contain high levels of skin compounds that both inhibit Na+- and K+-dependent adenosinetriphosphatase and antagonize the binding of ouabain to the enzyme. In species of Bufo and Atelopus, these compounds are relatively nonpolar bufodienolides, whereas Dendrophryniscus and Melanophryniscus contain more polar compounds of unknown structure. Skin extracts from 30 of 48 species of frogs representing an additional eight families contained relatively low levels of compounds that inhibit binding of ouabain to Na+,K+-adenosinetriphosphatase. The widespread occurrence of low levels of inhibitory compounds is consonant with the role for these compounds as physiological regulators of Na+,K+-adenosinetriphosphatase in amphibian skin; high levels in the Bufonidae probably also serve as a defense against some predators. PMID- 6245448 TI - Opiate analgesia: evidence for mediation by a subpopulation of opiate receptors. AB - Naloxazone, a hydrazone derivative of the opiate antagonist naloxone, has a high affinity for opiate receptor binding sites. Naloxazone injections reduce opiate receptor binding to extensively washed mouse brain membranes for more than 24 hours, suggesting that the effect is irreversible. High-affinity binding sites are abolished by this treatment, whereas low-affinity sites are unaffected. Naloxazone treatment blocks the analgesic effects of morphine for at least 24 hours but does not prevent death from high doses of morphine. Thus analgesic but nonlethal opiate effects may be mediated by the high-affinity subpopulation of opiate receptors. PMID- 6245449 TI - Single-shot channel activation accounts for duration of inhibitory postsynaptic potentials in a central neuron. AB - In the goldfish Mauthner cell, inhibitory postsynaptic currents evoked by intracellular stimulation of presynaptic neurons decay exponentially, with a mean time constant of 6.65 milliseconds. Analysis of membrane conductance fluctuations induced by iontophoresis of glycine and gamma-aminobutyric acid indicates a mean inhibitory channel lifetime of 7.15 milliseconds. The results thus suggest that the relaxation kinetics of activated inhibitory channels are rate-limiting during decay of the inhibitory postsynaptic current. PMID- 6245450 TI - [Primary mixed unilateral algias (author's transl)]. AB - Usually trigeminal neuralgia or tic douloureux and migrainous neuralgia or cluster headache are sharply opposed. But some rare cases of mixed facial unilateral algias associating both mechanisms are possible. Here is studied a series of 12 cases. One may distinguish: 1. one neuralgic vascular type. It starts by lightning and triggered hemifacial pain followed by tenderness and vaso secretory phenomenous of same topography; 2. the second is of vascular-neuralgic type. It starts like common cluster headache; the lightning pain occuring in the end of paroxysm. Only the first type -- neuralgic vascular -- is reactive to chimiotherapy (carbamazepine) or local antinevralgic procedures (thermocoagulation). PMID- 6245451 TI - [Headache of cervical origin. Critical study (author's transl)]. AB - When confronted to an occipito-cervical headache too often cervical etiology is proposed. Several cervical mechanisms are however possible: 1) neuralgic mechanism for the three first cervical segments. Any vertebral or intra-spinal lesion may affect the first three posterior roots; 2) muscular mechanism affecting cranio-cervical muscles: role of posture; spinal unbalance; traumatic or acute rheumatic discovertebral lesion; 3) vascular (arterial) mechanism, much more unfrequent like vertebro-basilar insufficiency. The role of vegetative (sympathetic) system is practically inexistant. So cervicarthrose play no role when there is no arthro-muscular involvement with painful limitation of cervical movements. But the most important causes of posterior cephalalgia are not of cervical intracranial origin: they are tumours of posterior fossa; high blood pressure, and above all tension headache of psychic origin. PMID- 6245452 TI - [Cephalee d'effort or cough headache. About 43 cases (author's transl)]. AB - "Cephalee d'effort" (Tinel C.E.) is provocated by any physical effort: taking up a heavy weight, but also coughing, sneezing, laughing, going to stool. Pain is usually localized, abrupt in onset and of short duration. One may distinguish: 1) C.E. secondary to intracranial lesions, cranial traumatism, tumours of posterior fossa, syringomyelobulbia, Arnold-Chiari malformation, Paget disease, etc... 2) Isolated or primary C.E.: they occur mainly in men after fifty. Recurrence is capricious. Prognosis is good. Three mechanisms are possible: acute veinous hypertension of dural sinuses; sharp C.S.F. pressure rise, dural traction. The denomination of "cephalee d'effort" given by Tinel in 1932 is preferred to this of cough headache given by Sir Charles Symonds in 1956; because of the anteriority and wider conception of causal physical efforts, including cough. PMID- 6245453 TI - [Involvement of the central nervous system in Behcet's syndrome. Report of two cases (author's transl)]. AB - After presenting two personal observations, the authors underline the fact that the neurological manifestations of Behcet's disease are more frequent than they were supposed to be. Their symptoms are overly manifold but have in common constant abnormality in the cerebrospinal fluid when an attack occurs. The affection is a very serious one demanding an early and well established diagnosis only to be obtained thanks to a clinical examination. Corticosteroid therapy (1 mg/kg per day) either alone or associated with immuno-suppressive therapy may check the attack. Preventing relapses implies a non-stop treatment. Immuno suppressive therapy seems to be the most efficient one. PMID- 6245454 TI - [Iatrogenic arthritis after intestinal by-pass as a treatment for obesity (author's transl)]. AB - The authors report three observations of patients having suffered from arthralgias as an aftermath of intestinal by-pass for treatment of refractory obesity. They remind the main troubles cropping up after such surgical treatment and refer to the data already existing in the literature dealing with articular manifestations. They think this pathology is in keeping with arthritis already reported in inflammatory colitis and they suggest a similar pathogeny. PMID- 6245455 TI - [Progressive changes in coronary lesions studied by iterative coronarography in operated and non-operated patients (author's transl)]. AB - The authors studied progressive changes in coronary atheromatous lesions by iterative coronarography after an average period of 2 years, and at least 1 year, in operated (50 cases with a single aortocoronary venous shunt), or non-operated patients (24 cases). The results were compared to those reported in previously published papers, using as a reference, the monthly percentage deterioration in pre-existing lesions. In the non-operated patients (24 cases), results were comparable to those obtained by some authors, and showed that the lesions deteriorated by about 10% each year. In operated patients, the authors refute the previously accepted statement that operative therapy causes a more rapid worsening of the lesions. It certainly appears to be false when the graft is occluded (17 cases); and seems to be at least premature when it is permeable (33 cases). The authors also attempted to find a correlation which could be used to assess probable evolutory changes in coronary lesions. This had previously been envisaged by Rosch, but it is difficult to establish, and further complementary studies are necessary. PMID- 6245456 TI - [Renal staghorn calculi in adults. A study of eighty patients with ninety two calculi (author's transl)]. AB - A homogeneous sery dealing with 80 cases of staghorn calculi in adult patients is examined from clinical and therapeutic points of view. Among 75 operated patients, 8 bilaterally, 67 conservative operations were performed. Enlarged intra-sinusal pyelotomy gives the best short and long-term results and is the surgical procedure of choice. PMID- 6245457 TI - [Retroperitoneal cystic schwannoma. Review of literature. A case report (author's transl)]. AB - One case of retroperitoneal cystic schwannoma (neurilemoma) in a 35 year old woman is described. With a review of literature are analysed the clinical and anatomo-pathological features of this uncommon tumour and the methods of diagnosis and surgical treatment. PMID- 6245458 TI - [Rolandic paroxysmal epilepsy. Prognostic, electric, clinical limits. Study of 28 cases (author's transl)]. AB - Rolandic paroxysmal epilepsy remains a frequent eventuality in children and even more so than the "minor epilepsy". In more cases, it is easily diagnosed and enables the physician to reassure the family which is usually frightened by the word "epilepsy". Both complementary examinations and therapeutic excesses can also be reduced. In a number of cases, the diagnosis may be questionable. It seems that the features of certain crises, the post-critical deficit, the massive anomalies in post-critical electroencephalogram, the reactivation of the crises during puberty are as many factors liable to moderate a too securising optimism both for the physician and the patient. PMID- 6245459 TI - [Retention of urine caused by fecaloma in the course of a Guillain-Barre syndrome (author's transl)]. AB - Sphincteral disorders are very rarely seen in a Guillain-Barre syndrome. The authors report a case of such a syndrome in a woman, in the course of which a retention of urine appeared making diagnosis more difficult. The cause actually was mechanical. PMID- 6245460 TI - [Interest of tiapride in digestive endoscopy (author's transl)]. AB - Used in monotherapy in 20 patients as a premedication for a high digestive endoscopy, tiapride gave results quite comparable to those of substances used till now (anticholinergic, anxiolytic) with tolerance on the whole excellent. PMID- 6245461 TI - [Liver abscess and visceral linguatulosis with Linguatula Serrata. A case report with radiologic and histologic studies (author's transl)]. AB - The authors report a case of hepatic Liguatulosis with "Linguatula Serrata". A nympha of this parasite was found encysted and calcified in a liver abscess. PMID- 6245462 TI - [Trigeminal sensory neuropathy and Sharp's syndrome (author's transl)]. AB - Neurological manifestations are rarely observed with mixed connective tissue disease (MCTD). The most frequent is a trigeminal sensory neuropathy which sometimes appeared as an early symptom. We report a new case of bilateral isolated trigeminal sensory neuropathy during M.C.T.D. Similitudes can be drawn with trigeminal neuropathies observed in connective tissue diseases such as scleroderma. Mechanisms are discussed. PMID- 6245463 TI - [Gynecomastia and iodine induced thyrotoxicosis during a benziodarone treatment (author's transl)]. AB - Hyperthyroidism gives seldom a gynecomastia. We describe an iodine induced thyrotoxicosis, after benziodarone, which is associated with a gynecomastia. Hyperthyroidism and gynecomastia vanish after stop of the drug. PMID- 6245464 TI - [Spontaneous rupture of the spleen during chronic pancreatitis. A report on two new cases (author's transl)]. AB - Spontaneous spleen rupture during chronic pancreatitis is scarcely seen. About 2 personal cases, the authors study 15 published cases. The spleen break can occur in patients with a known chronic pancreatitis, or with pancreatic signs, or without any symptomatology. Diagnosis is hard: spontaneous spleen break often looks like an acute pancreatitis. The high frequency of associated left pleural effusion is significant. Arteriography is helpful when it is done. Splenectomy, often too late, is the right treatment. PMID- 6245465 TI - [Skin lesions revealing a glucagonoma (author's transl)]. AB - About a case of necrolytic migratory erythema erythema revealing a malignant pancreatic glucagonoma, the authors compare the results of their study with the 25 cases published in the world. PMID- 6245466 TI - [Acquired idiopathic sideroblastic anemia (author's transl)]. AB - The authors consider the clinical and biological data of Acquired Idiopathic Sideroblastic Anemia (AISA). The physiopathology of the syndrome is discussed; the relationships between pathologic sideroblastosis, dyserythropoiesis and ferrokinetic modifications are pointed out. The associated abnormalities of granulocytic and megacaryocytic series linked AISA to other myelodysplasia. PMID- 6245468 TI - Carcinoma of the lung in progressive systemic sclerosis: a tabular review of the literature and a detailed report of the roentgenographic changes in two cases. AB - The association of various pathologic changes in the lung, especially interstitial fibrosis, in progressive systemic sclerosis is a recognized occurrence. Usually it is not the site of development of a malignancy. As a corollary the literature contains a number of examples of carcinoma developing in the lung in patients with idiopathic basilar fibrosis unrelated to PSS. Currently, we have reviewed the available literature and found a satisfactory description of 44 cases of carcinoma of the lung in patients with progressive systemic sclerosis. Also, there are brief descriptions of 10 cases of pulmonary carcinoma and PSS. The development of a malignancy superimposed upon the chronic changes in the lung, associated with the systemic sclerosing process may be related pathogenically to an altered immunologic response. PMID- 6245467 TI - [Fenfluramine and its effects on the sympathetic nervous system in man (author's transl)]. PMID- 6245469 TI - New pituitary peptide relationships. AB - A glycoprotein molecule discovered in pituitary glands of experimental animals is thought to be the precursor molecule for the pituitary peptides ACTH and beta lipotropin, molecules themselves known to contain the amino acid sequences of several smaller peptides subsequently isolated. Evidence now exists to suggest the enzymatic cleavage of ACTH to alpha-MSH and corticotropic-like intermediate lobe peptide (CLIP), pituitary peptides with effects upon the fetal pituitary gland. Beta-lipotropin is probable the prohormone for the peptides beta-MSH, gamma-lipotropin, methionine-enkephalin, and beta-endorphin. Beta-MSH may enchance the known physiologic effects of mammalian central nervous system transmitters, while the enkephalins and beta-endorphin have been shown to exhibit opioid analgesic properties as well as effects upon behavior, temperature regulation, and the release of growth hormone and prolactin. Homologies among their amino acid sequences and evidence for prohormone activity in ACTH, beta lipotropin, and the putative ACTH-beta lipotropin precursor suggest the possibility of the presence of a previously unsuspected interrelationship in the synthesis and release of these various pituitary peptides. PMID- 6245470 TI - [Effect of the organization of the after care and rehabilitation departments on the utilization of the hospital bed resources]. PMID- 6245471 TI - Choriocarcinoma and invasive mole. PMID- 6245472 TI - Secretion of alpha 1-antitrypsin by an established human hepatoma cell line and by human/mouse hybrids. AB - The human hepatoma cell line SK-HEP-1 has been shown by radioimmunoelectrophoresis to synthesize and secrete a protein which coprecipitates with human alpha 1-antitrypsin. This protein was indistinguishable from serum alpha 1-antitrypsin in terms of electrophoretic mobility, apparent subunit molecular weight (47,000), and binding to concanavalin-A. The protein identified as alpha 1-antitrypsin (alpha 1 AT) was secreted by seven clones derived from SK-HEP-1 and by twelve out of eighteen hybrid clones derived from the fusion of SK-HEP-1 with mouse RAG cells. There was no correlation between the expression of alpha 1 AT and that of human enzymes assigned to sixteen different autosomes. There was an imperfect correlation between the expression of alpha 1 AT and of the two chromosome 9 marker enzymes AK1 and AK3 (two discordant clones). PMID- 6245473 TI - Isolation of multiple classes of mutants of CHO cells resistant to cyclic AMP. AB - From mutagenized Chinese hamster ovary (CHO) cells we have isolated, in a single step, 11 independent mutants resistant to the growth-inhibitory effects of 8-Br cyclic AMP, cholera toxin, and methylisobutylxanthine. Two major classes and several subclasses of mutants were obtained. Mutants from all classes have a normal doubling time. None of the mutants respond to cyclic AMP treatment with increased flattening and elongation as do the parental cells. Members of the first class have an altered protein kinase activity which has either an increased Ka for cyclic AMP or an absent response to cyclic AMP. Most of those mutations which result in a protein kinase with increased Ka for cyclic AMP (6/11) are dominant in somatic cell hybrids. Those mutations which result in a protein kinase with little or no response to cyclic AMP (3/11) are recessive. Members of the second major class (2/11) have normal levels of basal and cyclic AMP dependent protein kinase activity. One is recessive and one is dominant by genetic tests. The basis for the defect in this second class of mutants has not been determined. PMID- 6245474 TI - Identical cancers in husband and wife. AB - Eleven married couples having histologically identical malignant tumors have been encountered: two couples with melanoma; three with carcinoma of the breast; two with carcinoma of the kidney, and one couple each with fibrosarcoma; carcinoma of the floor of the mouth; carcinoma of the colon and rectum, and carcinoma of the nasopharynx. The interval until the spouse of the patient with cancer was diagnosed to have cancer was within five years in all but three instances. The clinical course of the disease tended to be similar in both husband and wife. Generally, the longer the couple had been married, the more successful was their treatment. Those tumors described, as well as those identical cancers of husband and wife previously reported, have been suggested either experimentally or indirectly to have viral relationships. PMID- 6245475 TI - Granular cell myoblastoma. AB - The experience at this university between 1954 and 1978 included 96 granular cell myoblastomas in 67 patients. The unusual locations of the tumors were the breast, bronchus, vocal cord, stomach and rectus sheath. An extremely rare invasive squamous carcinoma developed from a lesion of the larynx with pseudoepitheliomatous hyperplasia of the overlying dpithelium. Two patients with malignant granular cell myoblastoma have been encountered. PMID- 6245476 TI - Treatment of a brain tumor with BCG cell wall preparation. PMID- 6245477 TI - Arterial catheter embolization followed by surgery for large chemodectoma. AB - We report on the first successful preoperative arterial catheter embolization of a large neck chemodectoma followed by its surgical removal. A 21-year-old man presented with a large mass in the right neck diagnosed 5 years previously by biopsy as a chemodectoma. The patient previously had refused therapy. Because of concern over the large size of the mass and increasing difficulty in swallowing, he agreed to undergo therapy. The patient underwent selective occlusion of the occipital and posterior auricular arteries and the thyrocervical trunk using Ivalon sponge emboli injected through a No. 5 Fr Hanafee catheter. A postembolization arteriogram showed 90% occlusion of tumor vascularity and 30% decrease in size of the tumor. This was followed by removal of the tumor surgically. A review of the difficult management of the patient is presented, and implications for future use of the combined procedures are discussed. PMID- 6245478 TI - Liquoid and platelet aggregation. PMID- 6245479 TI - Effect of adenosine 5'-diphosphate and shape change on 5-hydroxytryptamine uptake by human blood platelets. PMID- 6245480 TI - [Adenovirus keratoconjunctivitis]. PMID- 6245481 TI - [Stiff and lame animals]. PMID- 6245482 TI - Changes in glucose-6-phosphatase activity in liver and kidney of rats treated with a single large dose of fluoride. PMID- 6245483 TI - The effect of different diets or mineral oil on liver pathology and polybrominated biphenyl concentration in tissues. PMID- 6245484 TI - Antibody to hepatitis B surface antigen: immunochemical purification from standard immune serum globulin. AB - Hepatitis B surface antigen (HBsAg) may be insolubilized onto a controlled pore glass (CPG) matrix by simple adsorption from acidified serum or plasma. The resultant complex has the properties of an HBsAg-specific immunoadsorbent. In this study, CPG-HBsAg complexes have been used to adsorb anti-HBs from standard immune serum globulin. Specific antibodies were eluted with acidic or chaotropic buffers. Recoveries ranging from 29 to 46 per cent, with purifications of approximately 1000-fold were obtained. Two procedures designed to inactivate hepatitis B virus had no effect upon the immunoadsorbent properties of the CPG HBsAg complex. The possibility of using this simple method to prepare hepatitis B immune globulin is discussed. PMID- 6245485 TI - Distribution of polybrominated biphenyls (PBB) among fractions derived from contaminated human plasma. AB - The introduction of polybrominated biphenyls (PBB) into the Michigan food chain resulted in the presence of low levels of PBB in plasma pools used for blood fractionation. Pooled plasma lots contained an average of 1.0 +/- 0.2 ng/ml of PBB, while antihemophilic factor, fibrinogen, and immune serum globulin did not contain detectable amounts of PBB. Albumin (25%) lots contained an average of 2.0 +/- 0.4 ng/ml of PBB. Analysis of old lots showed that PBB first appeared in an albumin lot filled in January, 1974. Plasma used in preparing this lot was drawn during the period when PBB was entering the food chain. The results indicated that the behavior of chemical pollutants is an important consideration when fractionating blood or plasma collected in areas where industrial or environmental pollution have occurred. PMID- 6245486 TI - Varicella-zoster virus infection after marrow transplantation for aplastic anemia or leukemia. AB - Nearly one-half of marrow transplant recipients who survive at least 6 months develop varicella-zoster virus (VZV) infection. Of 92 cases studied, 82 occurred within the first 12 months after transplant. Only one patient had recurrent infection. Seventy-seven patients had herpes zoster, 22 with subsequent cutaneous dissemination, and 15 had varicella. The overall mortality rate was 8%, and all deaths occurred within 9 months of transplant. Twenty-six of 32 patients studied had significant rises in VZV antibody during recovery. Among patients with acute leukemia, those with syngeneic transplants had a significantly lower incidence of VZV infection than those with allogeneic transplants. Incidence was slightly, but not significantly, decreased among patients with aplastic anemia. In contrast to other infections, the incidence of VZV infection was not influenced by graft versus-host disease or predicted by the results of dinitrochlorobenzene skin testing. PMID- 6245487 TI - An improved technique for the isolation and identification of mammalian islets of Langerhans. PMID- 6245488 TI - Use of cell surface localizing antihepatoma antibody for tumor imaging and therapy with drug-linked antibody. PMID- 6245489 TI - Active secretion of cytoskeletal and mechanochemical proteins in EBV-genome positive human lymphocytes. PMID- 6245490 TI - Preliminary characterisation of the Sersenk strain of goat pox virus. AB - The Sersenk strain of goat pox virus first isolated in Iraq, grew on chorioallantoic membranes (CAM) of developing chicken embryos producing generalised large pocks, 2 to 3 mm in diameter, on the third day post inoculation. The virus killed the inoculated embryos. Replication of the virus in primary cultures of lamb testis cells induced a cytopathic effect (CPE) and plaque formation characteristic of pox viruses. It was antigenically related to reference strains of goat pox and sheep pox viruses. The virus was sensitive to ether and chloroform, failed to agglutinate erythrocytes and was strictly pathogenic to goats. PMID- 6245491 TI - [Angiotensin converting enzyme. Physiopathological and clinical aspects]. PMID- 6245492 TI - [Angiotensin converting enzyme as a diagnostic aid in newly diagnosed sarcoidosis compared with pulmonary cancer and tuberculosis]. PMID- 6245493 TI - Ultrasound-induced changes in rates of influx and efflux of potassium ions in rat thymocytes in vitro. PMID- 6245494 TI - [The incubation period of gas gangrene (author's transl)]. PMID- 6245495 TI - [Radioisotope teletherapy of prostatic cancer]. PMID- 6245496 TI - [Rare kidney tumors in children]. PMID- 6245497 TI - Hidrocystoma and adenoma of apocrine anal glands. AB - Five cases of apocrine hidrocystoma of the anal glands are described, two of which are dealt with in detail, as they were a primary cause of the patients' complaints. The three additional cases were found incidentally during histologic examination of hemorrhoidectomy specimens. All five patients were women between 32 and 65 years of age. The similarities with the better known cutanous hidrocystomas of other sites harbouring apocrine sweat glands are emphasized and the morphogenesis of these lesions is considered. In addition, a rare adenoma of the apocrine anal glands in a 46 year old woman is described and the problems of diagnostic classification in examples lacking predominantly papillary structures are discussed. PMID- 6245498 TI - Role of fast-sedimenting SV40 nucleoprotein complexes in virus assembly. PMID- 6245499 TI - Isolation and characterization of various forms of simian virus 40 DNA-protein complexes. PMID- 6245500 TI - The white pock mutants of rabbit poxvirus. I. Spontaneous host range mutants contain deletions. PMID- 6245501 TI - A physical gene map of the bacteriophage P22 late region: genetic analysis of cloned fragments of P22 DNA. PMID- 6245502 TI - Chemical crosslinking of proteins in avian sarcoma and leukemia viruses. PMID- 6245503 TI - Inhibition of Escherichia coli exonuclease V by bacteriophage Mu. PMID- 6245504 TI - Phosphonoformate inhibits synthesis of Epstein-Barr virus (EBV) capsid antigen and transformation of human cord blood lymphocytes by EBV. PMID- 6245505 TI - Epstein-Barr virus-induced proteins. III. Analysis of polypeptides from P3HR-1 EBV-superinfected NC37 cells by immunoprecipitation. PMID- 6245506 TI - Genome organization of retroviruses IX. Analysis of the genomes of Friend spleen focus-forming (F-SFFV) and helper murine leukemia viruses by heteroduplex formation. PMID- 6245507 TI - A transfection assay for transformation by feline sarcoma virus proviral DNA. PMID- 6245508 TI - A comparative study of the lipids of plasma membranes of normal cells and those infected and transformed by Rous sarcoma virus. PMID- 6245509 TI - Assembly of adeno-associated virus. PMID- 6245510 TI - Genetic and physical evidence for the polarity of transcription of the thymidine kinase gene of herpes simplex virus. PMID- 6245511 TI - Avian oncovirus proteins expressed on the surface of infected cells. PMID- 6245512 TI - The role of large T antigen in simian virus 40-induced reactivation of silent rRNA genes in human-mouse hybrid cells. PMID- 6245513 TI - Palindrome-like dimers of double-stranded RNA of encephalomyocarditis virus. PMID- 6245514 TI - Radioimmune precipitation study comparing the Epstein-Barr virus membrane antigens expressed on P3HR-1 virus-superinfected Raji cells to those expressed on cells in a B-95 virus-transformed producer culture activated with tumor-promoting agent (TPA). PMID- 6245515 TI - Replication of herpesvirus DNA. VI. Virions containing either isomer of pseudorabies virus DNA are infectious. PMID- 6245516 TI - Genetic reassortment of influenza A viruses in the intestinal tract of ducks. PMID- 6245517 TI - Inhibition by acyclovir of cell growth and DNA synthesis of cells biochemically transformed with herpesvirus genetic information. PMID- 6245518 TI - Coordinate expression of the 48K host nuclear phosphoprotein and SV40 T ag upon primary infection of mouse cells. PMID- 6245519 TI - The expression of pp60src and its associated protein kinase activity in cells infected with different transformation-defective temperature-sensitive mutants of Rous sarcoma virus. PMID- 6245520 TI - Comparison of wild-type BK virus DNA and BK virion DNA rescued from virus transformed BHK cells. PMID- 6245521 TI - Isolation of complementary DNA unique to the genome of avian myeloblastosis virus (AMV). PMID- 6245522 TI - Inhibition of vesicular stomatitis virus replication by adenosine. PMID- 6245523 TI - State of viral DNA in BK virus-transformed rabbit cells. PMID- 6245524 TI - Studies on tumorigenicity of cells persistently infected with vesicular stomatitis virus in nude mice. PMID- 6245525 TI - Organization and expression of endogenous murine mammary tumor virus genes in mice congenic at the H-2 complex. PMID- 6245526 TI - DNA synthesis in isolated hepatocytes infected with herpesviruses. PMID- 6245527 TI - A VSV mutant synthesizes a large excess of functional mRNA but produces less viral protein than its wild-type parent. PMID- 6245528 TI - The evolution of baboon endogenous type C virus: related sequences in the DNA of distant species. PMID- 6245529 TI - Activation of mouse retrovirus by herpes simplex virus type 1 cloned DNA fragments. PMID- 6245530 TI - Occurrence of free, defective viral DNA in a hamster tumor induced by human papovavirus BK. PMID- 6245531 TI - Studies of the long-term effect of Fv-1 gene restriction in clones of NIH/3T3 cells infected with murine leukemia virus. PMID- 6245532 TI - The early proteins of the nondefective Ad2-SV40 hybrid viruses: the 19K glycoprotein is coded by Ad2 early region 3. PMID- 6245533 TI - Biogenesis of poxviruses: preliminary characterization of conditional lethal mutants of vaccinia virus defective in DNA synthesis. PMID- 6245534 TI - Novel nonconditional mutants in the src gene of Rous sarcoma virus: isolation and preliminary characterization. PMID- 6245535 TI - [Early diagnosis and treatment of anaerobic infection]. PMID- 6245537 TI - [5-nucleotidase activity in viral hepatitis]. PMID- 6245536 TI - [Change in the nonesterified fatty acid makeup of Shigella flexneri No. 15172 type 3a in the process of passage on developing chick embryos]. AB - Composition of nonesterified fatty acids/NEFAj from Shigella Flexneri was similar to that from other Gram-negative bacteria of the enteritic group. At the same time, NEFA of the dysenteric bacteria contained comparatively high amount of branched and cyclopropane-bearing fatty acids. Adaptation of Shigella Flexneri in the medium of developing chicken embryo led to a distinct increase in total NEFA content as well as of cyclopropane-bearing and saturated fatty acids in the bacteria and to a decrease in content of branched-chain and unsaturated fatty acids. Total content of NEFA and of unsaturated fatty acids was increased, but their qualitative composition became poor in amnions of developing chicken embryons under conditions of their infection with the Shigella. PMID- 6245538 TI - Medical Grand Rounds from the West Virginia University Medical Center Mononucleosis Syndromes. PMID- 6245539 TI - [Effect of lipiodol "ultra-fluid" used for intrathyroid lymphography on the blood serum levels of thyroxine and triiodothyronine]. PMID- 6245540 TI - [Diagnostic difficulties and differential diagnosis of islet cell tumor]. PMID- 6245541 TI - [Rapi-Tex IgM test for detection of intrauterine infections of newborn infants]. PMID- 6245542 TI - Study of phosphagens in two trematodes. AB - Extracts from the adults of two trematodes Fasciola gigantica and Paramphistomum explanatum have been shown to contain three phosphagens, phosphoarginine, phosphocreatine, and phosphoglycocyamine. The three phosphokinases involved in the transphosphorylation of these phosphagens in both worms were inhibited by EDTA and mercuric ions while iodoacetate had no effect. PMID- 6245544 TI - [Colonic, rectal and anal carcinoma]. PMID- 6245543 TI - The mosquito Aedes aegypti (L.): evidence for three new proteinases. AB - The effect of inhibitors was studied on the proteolytic activity of crude extracts of the mosquito Aedes aegypti (L.), prepared 25 h after blood intake. This activity is only partially inhibited by the lima bean trypsin inhibitor (LBTI) or by EDTA. Experiments with mixed inhibitors are used to indicate that, apart from the well characterized trypsin-like enzymes, at least three other proteinases are present. These are an LBTI-resistant serine proteinase, a metal chelator-sensitive proteinase, and a proteinase which can only be inhibited by the ovomucoid inhibitor. These newly described proteinases are inactive against several model substrates developed for mammalian enzymes. They are partially separable by ion-exchange chromatography. PMID- 6245545 TI - [Postoperative disorders of lung perfusion and their therapy]. PMID- 6245547 TI - ["Elementary" and "minimal" postsynaptic potentials]. PMID- 6245546 TI - [Transmission of information in systems regulating metabolic balance in the body]. PMID- 6245549 TI - [Regulation of salivary gland enzyme secretion]. PMID- 6245550 TI - Cancer trends: glioblastoma multiforme and radiation therapy. AB - After a century of experience with brain tumors, oncologists today can offer the patient with glioblastoma multiforme only limited survival time with the best treatments known today. Radiation therapy has prolonged survival, though not to significant degree. PMID- 6245548 TI - [Cortical mechanisms of modulating the sensation of pain]. PMID- 6245551 TI - Don't just do something.... PMID- 6245552 TI - [Interrelationship of microcirculation and systemic blood circulation in pathological conditions]. PMID- 6245553 TI - [Cyclic AMP content in the skin and the activity of lysosomal enzymes in the blood and skin in psoriasis]. PMID- 6245554 TI - Fine needle aspiration of breast carcinoma: a preliminary cytoprognostic study. AB - A cytologic grading method for fine needle aspiration smears was applied to 178 histologically confirmed breast carcinomas. Grade I defined a well-differentiated carcinoma, grade II a carcinoma with pleomorphic tumor cells and grade II an anaplastic carcinoma. The cell-to-cell relationship (topography) and the cytologic criteria contributed to the grading. Special attention was paid to grade III tumors, which have an unfavorable prognosis. The correlation of grading with the clinical course of the disease was evaluated after a 12-month followup. In 4% of the patients classified as having grade I disease, 8.9% as having grade II and 66% as having grade III, local recurrence of disease, metastasis or death was observed within one year. The contribution of cytologic grading to the prognosis of breast cancers is discussed. PMID- 6245555 TI - [Effect of lithium carbonate on the functional state and enzymatic activity of neutrophils in granulocytopenia]. PMID- 6245556 TI - Atypical senile dementia with widespread Lewy type inclusion in the cerebral cortex. AB - An atypical case of senile dementia is reported which shows senile plaques, neurofibrillary tangles, granulovacuolar degeneration, and Hirano bodies and numerous Lewy bodies in the pigmented neurons of the brain stem, and Lewy-body like inclusions in the cerebral cortex. The inclusions in the cerebral cortex had a strong resemblance to the Lewy bodies in the substantia nigra, though a few histochemical and ultrastructural differences were observed. The pathological findings were unexpected since the parkinsonian syndrome was not recognized. PMID- 6245558 TI - Growth characteristics of human pituitary adenomas in tissue and cell cultures. PMID- 6245557 TI - Regional differences in severity of cadmium-induced lesions in the peripheral nervous system in mice. PMID- 6245559 TI - The cord serum free amino acid levels in appropriate and small for gestational age newborn infants of mothers without clinical malnutrition in Abidjan. AB - The cord serum amino acid levels were determined in nine small for gestational age and fourteen appropriate for gestational age newborn infants of Abidjan, Ivory Coast. Small for gestational age newborns had a significantly lower total amount of amino acids, but the characteristic deviation of the individual concentrations and the high glycine/valine ratio seen in experimental and clinical protein deficiency were not found. PMID- 6245560 TI - Enzyme linked immunosorbent assay (ELISA) for determination of IgG antibodies to human cytomegalovirus. AB - A solid-phase enzyme linked immunosorbent assay (ELISA) for determination of IgG antibodies to cytomegalovirus (CMV) is described. The assay used purified CMV and extracts of CMV infected cells as antigen. Antigens were desiccated onto the bottom surface of polystyrene microcuvettes. The antibodies bound to the antigens were assayed by anti-IgG-alkaline phosphate conjugate followed by addition of the enzyme substrate. Titration curves have been obtained from the sera of 35 blood donors and of 23 patients. Comparison of results obtained by ELISA with those obtained by complement fixation (CF) shows that there is agreement between the tests. Both purified CMV and extracts of CMV infected cells were found to be suitable antigens. Purified CMV was of value particularly in those sera which show high reactivity against control antigen. The ELISA technique described is approximately 412 to 548 times more sensitive than the CF test when purified CMV or extracts of CMV infected cells, respectively, are used as antigens. No significant heterotypic rise to CMV was observed by ELISA in three sets of sera with seroconversion to herpes simplex virus. The ELISA technique gives objective results, is easily performed, and may be adaptable as a routine test both for serological diagnosis of CMV infection and for screening of the general population. PMID- 6245561 TI - 30 Min ACTH stimulation test as predictor of hypothalamic-pituitary adrenocortical function. Comparison with metyrapone test. AB - In 32 subjects the hypothalamic-pituitary-adrenocortical (HPA) response to metyrapone was found to correlate significantly with the adrenocortical response to exogenous ACTH. This report provides additional evidence suggesting that a 30 min exogenous ACTH stimulation test accurately predicts the integrated responsiveness of the HPA system to various stimuli. PMID- 6245562 TI - Ultra-microcrystals in pyrophosphate arthropathy. Crystal identification and case report. AB - A patient with pyrophosphate arthropathy is reported who had no calcifications on joint radiographs, and no crystals were found in polarized light microscopy of the synovial fluid. Using techniques for idenfication of crystals at the ultrastructural level, abundant small (less than or equal to 1 mu) pyrophosphate crystals were recognized and identified. The possibility of "ultramicrocrystal depositions", including pyrophosphate arthropathy, is important to consider in acute arthritides since small crystals might cause more intense inflammation and be the cause of arthritides, hitherto not possible to classify. PMID- 6245563 TI - Receptors for E and F prostaglandins in airways. AB - Determination of dose/response relationships for E and F PGs in guinea pig trachea and human bronchial muscle in vitro indicates that mixed contractant and relaxant activities are present in different proportions in each PG. Further analysis of these effects, using (a) tachyphylaxis to individual PGs and (b) indomethacin as a PG antagonist, argues that two PG receptors exist on tracheobronchial muscle. Activation of one of these (chi receptor) leads to contraction, and of the other (psi receptor) to relaxation. Individual E and F PGs interact with these two receptors in different proportions. A third potent effect of PGs on airways is to elicit cough. That PGF2 alpha elicits cough but has very little relaxant activity, whereas certain PG analogs and PGE1 elicit cough but possess either no bronchomotor or almost entirely relaxant activity, argues that a third receptor (omega) exists, the activation of which elicits cough. PMID- 6245564 TI - Possible role for Ca2+-dependent arachidonate release and prostaglandin synthesis in expression of the action of osmolality on renal inner medullary cGMP. PMID- 6245565 TI - The renal prostaglandin system in central diabetes insipidus: effects of desamino arginine vasopressin. PMID- 6245566 TI - Prostaglandins of blood vessels and vessel reactivity in rats receiving sodium chloride and indomethacin. PMID- 6245567 TI - Prostacyclin release induced by bradykinin may contribute to the antihypertensive action of angiotensin-converting enzyme inhibitors. PMID- 6245568 TI - Blockage of partially obstructed coronary arteries with platelet thrombi: comparison between its prevention with cyclooxygenase inhibitors versus prostacyclin. AB - This study shows that in vivo, platelet aggregation occurs by both cyclooxygenase and noncyclooxygenase-dependent mechanisms, so that blockage of partially obstructed coronary arteries still occurs after cyclooxygenase inhibition if the obstruction is severe enough. Prostacyclin prevents blockage of the vessels under all conditions. Furthermore, prostacyclin's ability to block primary aggregation is enhanced after cyclooxygenase inhibition. PMID- 6245569 TI - Comparison of the effects of PGI2 and PGE1 on coronary and systemic hemodynamics and coronary arterial cyclic nucleotide levels in dogs. PMID- 6245570 TI - Angiotensin-induced prostacyclin release may contribute to the hypotensive action of converting enzyme inhibitors. PMID- 6245571 TI - Bilateral carotid body tumors and cyanotic heart disease. PMID- 6245572 TI - Abdominal CT in lung carcinoma. PMID- 6245574 TI - The significance of protein as a component of dietary fiber. PMID- 6245573 TI - Malnutrition during development: effects on later susceptibility to lead poisoning. PMID- 6245575 TI - The role of respiratory infection in intrathoracic petechiae. Implications for sudden infant death. AB - Intrathoracic petechiae are characteristic of the postmortem changes found in sudden infant death syndrome. The presence and distribution of these petechiae have been claimed as evidence for airway obstruction as the mechanism of death. In a group of young, mature rats that were free of infection, hypoxic asphyxia produced an insignificant number of petechiae, whereas in all littermates infected with an enzootic virus (Sendai) large numbers of petechiae with hypoxic asphyxia developed. Rats similarly infected, but killed with an overdose of pentobarbital sodium, had no petechiae. Most importantly, infected rats with unremitting airway obstruction were free of petechiae. Thus, the experimental conditions necessary for the presence of intrathoracic petechiae are profound hypoxia and infection, with persistent circulation and respiratory effort; persistent airway obstruction does not produce petechiae, with or without infection. PMID- 6245576 TI - Effect of prolactin on phospholipid biosynthesis by alveolar cell carcinoma (A549) in monolayer tissue culture. AB - By means of an alveolar cell carcinoma (A549) model, the effect of prolactin on pulmonary surfactant phospholipid biosynthesis was investigated. Preliminary results suggest that phosphatidylcholine synthesis via the phosphatidic acid phosphohydrolase pathway in addition to phosphatidylglycerol may be stimulated by the presence of prolactin. PMID- 6245577 TI - Steroid production and responsiveness to gonadotropin in isolated stromal tissue of human postmenopausal ovaries. AB - Specimens from the ovarian cortical stroma of 15 postmenopausal women were examined histologically and were incubated for 4 hours in Krebs' bicarbonate buffer containing 5.5 mM glucose and 1% bovine serum albumin. Specimens of normal postmenopausal stroma produced measurable amounts of androstenedione, estradiol, and progesterone in vitro. Specimens with stromal hyperplasia produced larger amounts of androstenedione and estradiol than those with normal stroma. Androstenedione was the predominant steroid produced in both groups. The nonnegligible formation of estradiol indicated an aromatizing capacity of the stromal tissue. The addition of hCG elicited a significant increase in cyclic AMP formation in specimens from ovaries with stromal hyperplasia, indicating a preserved responsiveness to gonadotropin in this type of ovaries. PMID- 6245578 TI - Basal cell-like carcinoma in the upper third of the vagina. PMID- 6245579 TI - A positive proof for the theory of coelomic metaplasia. PMID- 6245581 TI - cAMP-stimulated cation cotransport in avian erythrocytes: inhibition by "loop" diuretics. AB - The effect of a series of diuretically active substituted 3-aminobenzoic acid derivatives and related compounds was investigated on a cyclic AMP-activated Na+ K+ cotransport system in avian erythrocytes. A good correlation between the diuretic potency of this class of "loop" diuretics in the dog and their inhibition of cation cotransport in turkey erythrocytes was found. Selected thiazide-type diuretics were found to be ineffective. The most active compound tested (3-benzylamino-4-phenylthio-5-sulfamoylbenzoic acid) had an effective dose50 of 4.6 x 10(-8) M in the avian system, and was about 5 times more potent than bumetanide and 500 times more potent than furosemide in this regard. The diuretics appear to interact directly with the cation transport system itself, and not with some antecedent step in the sequence of events from intracellular cAMP accumulation to stimulation of transport. The compounds tested did not appear to compete at Na+- or K+-binding sites on the transport system. The similarity in the structure-activity relationship of these agents in the avian erythrocyte and the kidney suggests that the avian erythrocyte may be a useful model for analysis both of the diuretic-sensitive transport system of the mammalian kidney, and of the molecular mechanism of loop diuretic action. PMID- 6245580 TI - Estrogen and endometrial cancer: cases and two control groups from North Carolina. PMID- 6245582 TI - Heat production and Na+-K+-ATPase enzyme units in lean and obese (ob/ob) mice. PMID- 6245584 TI - Bicarbonate transport by proximal tubules: effect of parathyroid hormone and dibutyryl cyclic AMP. PMID- 6245583 TI - hCG-Leydig cell functional binding kinetics: threshold and nonlinearity in response. AB - Functional kinetic methods, developed to measure the interaction of human chorionic gonadotropin (hCG) with rat Leydig-cell receptors, appear to be useful tools for correlating response with receptor occupancy. In the functional procedures, hCG was allowed to bind to the cells (period I), the free hormone was removed by washing and/or antiserum treatment (period II), and the response of the cells was measured at 37 degrees C (period III). Once initiated, the response to hCG was stable throughout period III. Assuming a one-to-one relationship between occupancy and response during period III, we estimated the rate of association to be 10(8) M-1/min at 37 degrees C with an activation energy of 14 17 kcal/mol. Removal of sialic acid from hCG increased this rate; removal of other carbohydrate residues decreased it. Similar values for the kinetics of binding were observed when either steroidogenesis or cyclic AMP accumulation was measured, suggesting that the same receptor may mediate both processes. Use of either functional or direct (i.e., 125I-labeled hCG) methods to estimate response as a function of occupancy gave equal results, suggesting that most binding sites were coupled to a response. Response was nonlinearly coupled to occupany. Threshold amounts of hormone-receptor complex (0.1% total receptors testosterone synthesis; 2.7% total receptors cyclic AMP accumulation) were required to induce any response. Increased stimulation required progressively larger increments of receptor occupancy. The threshold was inversely proportional to the efficacy of the hCG derivative used and was reduced by the presence of isobutylmethylxanthine. PMID- 6245585 TI - Oxygen requirement of bicarbonate-dependent sodium reabsorption in the dog kidney. AB - The ratio between changes in sodium reabsorption and renal oxygen consumption (Na/O2) was measured in anesthetized dogs at high plasma bicarbonate concentration (32 +/- 1 mM); ethacrynic acid was infused continuously to prevent variations in transcellular NaCl reabsorption when sodium reabsorption was altered by varying plasma PCO2 and glomerular filtration rate (GFR). At high plasma PCO2 (110 mmHg) sodium reabsorption varied in proportion to GRF between 50 and 125% of control GFR (glomerulotubular balance). By reducing PCO2 to 20 mmHg, sodium reabsorption was reduced by 50-60% at constant GFR. The Na/O2 ratio was not significantly different during the two procedures and averaged 48 +/- 2. The ratio between changes in NaHCO3 reabsorption and oxygen consumption averaged 17 +/- 1, which is not significantly different from the Na/O2 ratio of Na-K-ATPase dependent sodium transport. We propose that NaHCO3 is admitted to the cell by Na+/H+ exchange and that sodium is actively transported by Na-K-ATPase across the peritubular cell membrane; NaHCO3 provides the osmotic force for paracellular reabsorption of water and NaCl (bicarbonate-dependent reabsorption) without additional energy requirement. PMID- 6245586 TI - Use of plasma membrane vesicles. AB - A summary of current methodologies employed to obtain and characterize epithelial plasma membrane vesicles is presented. Particular emphasis is placed on techniques to evaluate such parameters as homogeneity, tightness, orientation, and the percentage of active vesicles in a given vesicular population. Examples of isotopic, osmotic, and various probe techniques useful for quantitation of transport events and associated electrical phenomena are illustrated. Finally, the unique problems intrinsic to purification and reconstitution of transport proteins are briefly discussed. PMID- 6245587 TI - Probes of parietal cell function. AB - The site of acid secretion in the gastric mucosa has been inferred, but never proven. Using differential interference-contrast (Nomarski) microscopy an expansion of intracellular vacuoles was observed in the parietal cells of living rabbit gastric glands following histamine stimulation. A similar vacuolization occurring only in part of a parietal cell population could be induced by high concentrations of accumulated weak base, aminopyrine, in the absence of secretagogue. In high-K+ medium, 10(-3) M aminopyrine induced massive vacuolization in all parietal cells, consistent with the strong effect of high K+ in stimulating aminopyrine uptake by isolated glands. Electron micrographs showed that the apparent vacuoles correspond to the secretory canaliculi in various stages of swelling. Acridine orange, a fluorescent dye which is distributed across natural membranes as a function of a pH gradient and binds in a multimolecular fashion (stacking) to negative sites, was accumulated by gastric glands as a function of acid secretion. Visualization of such glands by fluorescence or a combination of Nomarski and fluorescence microscopy showed a red fluorescence in the expanding secretory canaliculi that was in sharp contrast to the green fluorescence in the rest of the cell. From these data it is concluded that the site of acid secretion is indeed the secretory canaliculus of the parietal cell. It is also possible that the formation of secretory canaliculi may be induced osmotically and that the peripheral "parietal" position and triangular shape of the parietal cell is necessary to allow expansion and oriented apical flow of HCl. PMID- 6245588 TI - Receptors for vasoactive intestinal peptide and secretin on small intestinal epithelial cells. AB - Binding of 125I-labeled vasoactive intestinal peptide (VIP) to dispersed enterocytes prepared from guinea pig small intestine was saturable, temperature dependent, and reversible, and reflected interaction of the labeled peptide with a single class of binding sites. Each enterocyte possessed approximately 60,000 binding sites and binding of the tracer to these sites could be inhibited by VIP [concentration for half-maximal effect (Kd), 12 nM] and by secretin (Kd greater than 1 micro M), but not by glucagon, gastrin, cholecystokinin, calcitonin, bombesin, litorin, physalaemin, substance P, eledoisin, serotonin, carbamylcholine, or histamine. With VIP and secretin, there was a close correlation between the relative potency for inhibition of binding of 125I-VIP and that for increasing cellular cAMP. For a given peptide, however, a 10-fold higher concentration was required for half-maximal inhibition of binding than for half-maximal stimulation of cellular cAMP. In addition to inhibiting binding of 125I-VIP and increasing cellular cAMP in enterocytes, secretin caused an increase in short-circuit current across guinea pig small intestine in vitro. Prostaglandin E1 increased cellular cAMP, but did not alter binding of 125I-VIP and the increase in cAMP caused by prostaglandin E1 plus VIP or secretin was equal to the sum of the increase caused by each agent alone. PMID- 6245589 TI - Prejunctional cholinergic modulation of adrenergic neurotransmission in the cardiovascular system. AB - In the heart and in the blood vessel walls, complex adrenergic-cholinergic interactions occur both prejunctionally, at the level of the autonomic nerve terminals, and postjunctionally, at the level of the responding cells themselves. The principal prejunctional interaction appears to be an inhibition of the release of norepinephrine from adrenergic nerve terminals by the acetylcholine liberated from nearby cholinergic nerve endings. This inhibitory effect is mediated by muscarinic receptors located on the postganglionic sympathetic nerve terminals. The inhibitory effect of acetylcholine on cardiac and vascular tissues are therefore achieved in part by a direct influence of the cholinergic neurotransmitter on the cardiac and vascular muscle cells, and in part by an indirect influence on sympathetic neurotransmission. PMID- 6245590 TI - Tubular system membranes of teleost chloride cells: osmotic response and transport sites. AB - Chloride cells represent the sites of branchial osmoregulatory activity of teleosts. The cells undergo characteristic changes with osmotic challenge and the response is mediated by hormones. Either increased salinity or cortisol treatment will elicit well-known changes in chloride cells; these changes are clearly interrelated and may be collectively referred to as the "hyperosmotic response" of chloride cells. Fundamental features of the "hyperosmotic response" include proliferation and hypertrophy of chloride cells, an amplification of the cell's extensive tubular network or tubular system (TS), an increase in the specific activity of the transport-associated enzyme, Na-K-ATPase, and a concomitant increase in electrolyte transport. The TS displays frequent examples of continuity with the basolateral plasmalemma and the Na-K-ATPase enzyme complex resides in the membranes of the TS. The enzyme complex maintains its conventional polarity with regard to internal substrate and sodium binding sites and external or TS luminal surface, potassium, and ouabain binding sites. The luminal surface of the TS is anionic at pH 1.8 and above. The TS membranes display in situ, in isolation, and by freeze fracture, a characteristic asymmetric structure consisting of repeating particles; larger particles are associated with the cytoplasmic surface of the membrane and smaller particles with the external or luminal surface of tubules. The dimensions of the particles, and their disposition with respect to the cytoplasmic and external surfaces of the TS membrane, support the hypothesis that they are the visual manifestation of the transport-associated Na-K-ATPase complex. The TS and its associated transport activity represent essential components of a recently proposed paracellular transport model for chloride cells. The TS of the pseudobranch cell is also discussed in this review. PMID- 6245591 TI - Ion-secreting epithelia: chloride cells in the head region of Fundulus heteroclitus. AB - Transporting cells of ion-secreting epithelia are characterized by similar morphological patterns that include rich supplies of mitochondria, exotic patterns of surface amplification, and basolateral, plasma-membrane location of Na-K-ATPase, even though the direction of sodium transport across these epithelia is toward the apical side. Several new models for NaCl secretion propose that sodium, extruded into the intercellular space by Na-K-ATPase, reaches the apical side via the zonulae occludentes. Very recent freeze-fracture electron microscopy of avian salt gland and teleost chloride cells reveals that transporting cells are joined by simple, shallow zonulae occludentes. These observations lend morphological support to the concept that paracellular sodium ion permeation plays a central role in secretion. The chloride ion may traverse the epithelium via a transcellular route, entering the cell at the basolateral membrane by a chloride carrier linked to the cotransport of sodium down its electrochemical gradient into the cell. Finally, the chloride ion may exit the cell across the apical membrane by electrical forces. This review summarizes biochemical, morphological, and electrophysiological aspects of these new secretory models and the important contribution of a half century of research on teleost osmoregulatory mechanisms, including the chloride cell, to our understanding of sodium and chloride transport across secretory epithelia. PMID- 6245592 TI - Comparison of vertebrate salt-excreting organs. AB - Many marine vertebrates must excrete NaCl against a substantial chemical gradient to remain hypoionic to the environment. Salt secretion appears to be mediated by "chloride cells" found in the gills of many fish or in salt glands in elasmobranchs, reptiles, and birds. The ultrastructure of the cells is similar in all animals possessing them, as is the composition of the fluid they produce, and a common mode of function is suggested. However, the extant flux-force data cannot be reconciled with a single mechanism. They appear to suggest that various combinations of Na+-, K+-, and Cl--transport systems can operate in different epithelia, and that epithelial permeabilities may also differ. However, a solution approximately seawater in monovalent ion concentrations is produced in every case. PMID- 6245593 TI - Kinetic studies of ion transport by fish gill epithelium. PMID- 6245594 TI - Role of Na-K-ATPase in chloride cell function. AB - In seawater eels the efflux of sodium (and chloride) across the gill is directly proportional to the activity of Na-K-ATPase in homogenates of gill filaments. The rate of ion movement, however, is substantially greater than at the temperature of seawater. Na-K-ATPase is localized predominantly on the basolateral surface of the chloride cell so that ouabain inhibits from the blood side rather than from the apical or mucosal surface of chloride cells. Chloride, rather than sodium, is probably the actively transported ion species, and an attractive hypothesis for active chloride transport is one that invokes the cotransport of chloride with sodium across the basolateral membrane, the energy for which is supplied indirectly by the operation of the Na-K-ATPase pump. Exposure to freshwater sharply dissociates ion movements from Na-K-ATPase activity, possibly by changing the permeability of cell membranes to chloride movements. PMID- 6245595 TI - Role of C-4 pathway in crustacean chloride cell function. AB - A hypothetical model for the bioenergetic regulation of ion transport in the chloride cell of the larval crustacean salt gland is presented. Current data dealing with the ultrastructural, electrochemical, and biochemical events associated with cytodifferentiation of the crustacean (Artemia salina) salt excreting epithelia is compiled and tabulated. A C-4 dicarboxylic aicd pathway is postulated to serve as a facultative anaerobic shunt to meet the demands of the high rate of glycolysis required by salt-secreting epithelium. This mechanism involves the fixation of CO2 from exogenous bicarbonate while forming net amounts of metabolic water and high energy nucleotide equivalents from stored diGDP. PMID- 6245596 TI - Diarrhea in a non-hospitalized rural Salvadoran population: the role of enterotoxigenic Escherichia coli and rotavirus. AB - To determine the role of rotavirus, enterotoxigenic Escherichia coli and enteropathogenic E. coli in diarrheal disease of non-hospitalized children and adults living in rural El Salvador, stool specimens were collected from 156 persons with diarrhea and 134 age- and sex-matched controls over a 1-year period. Enterotoxigenic Escherichia coli (ETEC) were isolated as frequently from controls (13.4%) as from diarrhea cases (12.2%). Enteropathogenic E. coli were isolated from 13 cases (8.3%) and 10 (7.7%) controls. Rotavirus was demonstrated in only five of the 129 specimens from cases examined; the five persons infected were less than or equal to 3 years of age. No invasive E. coli were found. Serotyping of ETEC revealed serogroups of ETEC previously associated with enterotoxigenicity but was not helpful in separating infection from disease. The etiology of diarrhea in this rural, non-hospitalized population was complex. Isolation of a known pathogen did not prove etiology. The rotaviruses, which have been isolated frequently from hospitalized persons, were rare. Further laboratory and epidemiologic studies in such populations are needed to identify those factors that determine pathogenicity. PMID- 6245597 TI - Percutaneous needle biopsy of pulmonary lesions. AB - Percutaneous needle biopsy of lung lesions has proved useful in the diagnosis of tumors and infectious lesions of the lung. Accurate tissue diagnosis of tumors was obtained in 81 percent of attempts, and an accurate microbiologic diagnosis was obtained in 75 percent of infectious lesions. Eleven percent (23 of 213) of patients biopsied for tumor were spared diagnostic thoracotomy, and only one biopsy gave a false-positive result. There has been no mortality, and the only significant morbidity was a 12 percent incidence of pneumothorax necessitating chest tube insertion. The use of this technique in varied clinical settings has made it a valuable and often primary diagnostic tool for lung lesions. PMID- 6245598 TI - The role of the human neutrophil in the inflammatory reaction. PMID- 6245599 TI - Chemodectoma diagnosed by hypertension and tachycardia during anesthesia. PMID- 6245600 TI - Correlation between terbutaline serum levels, c-AMP plasma levels and FEV1 in normals and asthmatics after subcutaneous administration. AB - Terbutaline serum levels, c-AMP plasma levels and percentage improvement in FEV1, were strongly correlated after subcutaneous administration of terbutaline to normals (n = 6) and to asthmatics (n = 5). Changes in c-AMP plasma levels were similar in both normals and asthmatics after subcutaneous administration, denying a systemically beta-adrenergic defect to be present in asthmatics. PMID- 6245601 TI - Long-term stability of blood lymphocyte nuclear pocket prevalence in clinically normal adult dairy bulls. AB - A study on blood lymphocyte nuclear pocket (LNP) prevalence stability was made over a 2-year period on ten clinically normal adult Holstein-Friesian bulls. The design of the experiment included 3 categories of animals as follows: (a) 3 bovine leukosis virus (BLV)-seronegative bulls (N); (b) 4 BLV-seropositive bulls and initial low (less than 1.0%) blood LNP prevalence; and (c) 3 BLV-seropositive bulls with initial high (greater than or equal to 2.0%) blood LNP prevalence. Prevalences of LNP for individual animals in all three groups were stable as to category of initial designation during the 2-year period. All animals initially designated as seronegative or seropositive remained so throughout the experiment. Essentially, correspondence between LNP concentration and BLV serotiter was observed only in the seronegative group in which prevalence was low on all samples. Because increased LNP prevalence has been shown to be related to in vitro C-type BLV production and beacuse LNP prevalence appears to be stable, this measurement may be of discriminatory value in studies to develop criteria for the disposition of enzootic bovine leukosis seropositive cattle. PMID- 6245602 TI - Virus isolated and immunofluorescence in different organs of pigs infected with hemagglutinating encephalomyelitis virus. AB - Hemagglutinating encephalomyelitis virus (HEV; also designated vomiting and wasting disease virus) was inoculated oronasally in 26 colostrum-deprived pigs. Anorexia and vomition were seen after an incubation period of 4 to 6 days. In pigs killed during the incubation period or within 2 days after the onset of the clinical signs, HEV could be isolated regularly from the tonsils and the respiratory tract, irregularly from the digestive tract, rarely from the blood, and never from lymph nodes and spleen. The brainstem almost always contained virus after clinical signs appeared, but was only one positive during the incubation period. Olfactory bulb, cerebrum, cerebellum, and vagal nerve were also frequently virus positive in pigs which were ill when killed. The results of the examination by immunofluorescent antibody technique indicated that HEV multiplies in the epithelium lining the respiratory tract and the tonsillar crypts, in neuroepithelium of the nasal mucosa, and in neurons of the digestive tract. The neuronotropism of HEV was also shown by the presence of fluorescence in the perikaryon of neurons in the brainstem and in the trigeminal ganglion without the involvement of other cell types. The presence of viral antigens in the perikaryon of trigeminal sensory ganglion cells in pigs killed during the incubation period was considered as positive evidence for viral spread via nerves. PMID- 6245603 TI - Experimental infection of pigs with a new porcine enteric coronavirus, CV 777. AB - Cesarean-derived colostrum-deprived and conventionally reared pigs were orally inoculated with the coronavirus-like agent, CV 777, isolate from an outbreak of epizootic diarrhea in swine of all ages. Viral particles detected by electron microscopy in the feces and intestinal contents of inoculated pigs had the typical coronavirus morphology. The present studies provided further evidence that this coronavirus-like agent is different from the two known porcine coronaviruses, transmissible gastroenteritis virus and hemagglutinating encephalomyelitis virus. The experimental infection of pigs with this new agent resulted in vomiting, diarrhea, and dehydration. This coronavirus-like agent was shown to replicate in the epithelial cells covering the small intestinal villi but, unlike transmissible gastroenteritis virus, it also replicated in the epithelial cells covering the large intestinal villi. PMID- 6245604 TI - Ontogeny of host responses in ovine fetuses infected with bluetongue virus. AB - Ovine fetuses were inoculated (IM) with bluetongue virus (BTV) between the 50th and the 130th days of a 150-day gestation. At 10 to 15 days after virus was inoculated, the interstitial tissue of the fetal lung was diffusely infiltrated with large mononuclear leukocytes. By 20 days, unitized nodules of macrophages were seen in the interstitial tissue of the lung. The only gross alterations observed in infected fetuses were large lymph nodes and prominent lymphoid nodules within the spleen. Fetuses inoculated on the 80th day developed increased serum concentrations of immunoglobulin G (IgG) within 20 days after inoculation, whereas fetuses inoculated on the 100th gestational day and later developed increased concentrations of IgG by 10 days. Fetuses inoculated on the 80th gestational day also developed serum neutralizing antibodies by 20 days after infection. The BTV was recovered from fetuses which had serum neutalizing antibody. The sequential development of responses to BTV infection during ontogeny in ovine fetuses is discussed. PMID- 6245605 TI - Somatic cell hybrids of canine peritoneal macrophages and SV40-transformed human cells: derivation, characterization, and infection with Ehrlichia canis. AB - Somatic cell hybrids were obtained by fusion of canine peritoneal macrophages and SV40-transformed human skin fibroblasts. A cell line (WRH-2) was established from a single isolated hybrid clone. The WRH-2 cell line has been serially passaged 60 times and has a population doubling time of approximately 24 hours. Karyotypic analysis showed the modal number of chromosomes to be 80, with a selective segregation of canine chromosomes. Expression of incorporated canine DNA was substantiated by cellular enzyme activities and antigen expression. The susceptibility of 5% to 7% of WRH-2 cells to Ehrlichia canis infection was associated with phagocytic properties of these cells. Magnetic separation of phagocytic cells after ingestion of carbonyl iron resulted in a significant enhancement of the phagocytic population with a concomitant increase in the percentage of cells susceptible to ehrlichial infection. Serial passage of the selected subpopulation of hybird cells, however, resulted in a rapid diminution in the percentage of phagocytic cells. PMID- 6245606 TI - Caprine bluetongue virus isolations. AB - Viral isolation procedures demonstrated the presence of bluetongue virus serotypes 10, 11, and 17 in routine caprine accessions. The goats in this report showed one or more of the following signs or lesions: weakness, pulmonary disease, abortion, fetuses with developmental abnormalities, keratoconjunctivitis, anemia, and swollen joints. PMID- 6245607 TI - Cell-mediated immunity in Marek's disease: correlation of disease-related variables with immune responses in age-resistant chickens. AB - A sequential study of cytotoxic and mitogen stimulation responses of peripheral blood leukocytes (PBL) after inoculation with Marek's disease (MD) virus was done with the 7 x 15 chickens at 2 weeks of age (group 1) and at 12 weeks (group 3). Control groups were inoculated with chicken kidney cells at 2 weeks of age (group 2) and 12 weeks (group 4). During an 8-week observation period, morbidity and mortality were greater in group 1 chickens than in group 3 chickens. The cytotoxic response of PBL against an MD tumor cell line (MSB-1) was greater during the first 2 weeks after chickens in group 3 were inoculated than in group 1 chickens. Correlations did not exist between cell-mediated cytotoxic responses and severity of disease for individual group 1 chickens. However, PBL fo group 3 chickens that developed gross lesions of MD had reduced cytotoxic activities after an initial activity equal to, or greater than, the activities of chickens that survived without gross lesions. Phytohemagglutinin stimulation of PBL was depressed in both groups during weeks 1 to 3 after inoculation. Group 3 chickens had higher virus titers in PBL than group 1 chickens during weeks 1 to 3 after inoculation. The titers subsequently decreased below those for group 1 during the remainder of the experiment. PMID- 6245608 TI - Experimental induction of cutaneous streptococcal abscesses in swine as a sequela to swinepox. AB - Streptococcal abscesses were experimentally induced in skin of swine as a sequela to swinepox. Swinepox lesions were more uniform in distribution when infection was induced by IV injection of swinepox virus than when induced by lice (Haematopinus suis) or scarification of skin. The incubation period for swinepox was between 10 and 14 days when virus was administered IV. Cutaneous abscesses developed in swine given IV injection of streptococci 10 and 14 days after they were injected with swinepox virus, but not when they were given the streptococci 7 days after virus injection or simultaneously with virus injection. Abscesses did not develop when streptococci were applied topically to swinepox lesions. PMID- 6245609 TI - Evaluation of experimental subunit vaccines for infectious bovine rhinotracheitis. AB - Subunit infectious bovine rhinotracheitis (IBR) antigens were prepared by solubilization of IBR-virus infected cell cultures with nonionic detergents Triton X-100 and NP-40. When used with Freund's incomplete adjuvant, Triton X-100 and NP-40 subunit antigens induced high serum-neutralization titers in vaccinated calves. Two doses of Triton X-100 and NP-40 subunit vaccines prevented the appearance of clinical signs of disease in all vaccinated calves exposed 30 days after the second vaccinal dose to intranasal challenge exposure with Cooper strain of IBR virus. Furthermore, two doses of NP-40 subunit vaccine prevented shedding of the virus in all vaccinated calves after challenge exposure. PMID- 6245610 TI - Virucidal disinfectants and feline viruses. AB - Thirty-five commonly used commercial disinfectants (disinfectants, antiseptics, sanitizers, and detergents) were evaluated for their virucidal activity against three feline viruses; feline viral rhinotracheitis virus (a herpesvirus), feline calicivirus, and feline panleukopenia virus (a parvovirus). Disinfectants were diluted as recommended by the manufacturer and were reacted with virus for 10 minutes at room temperature. Viruses were separated from disinfectants by gel filtration in special centrifuge tubes, and were assayed for infectivity in feline cell cultures. All 22 products tested were virucidal for feline viral rhinotracheitis virus, 11 of 35 were virucidal for feline calicivirus, but only 3 of 27 tested were effective against feline panleukopenia virus. A 0.175% sodium hypochlorite solution was the most effective and practical broad-spectrum virucidal product used alone or in combination with other disinfectants/detergents. PMID- 6245611 TI - Combined dexamethasone-suppression cosyntropin-(synthetic ACTH-) stimulation test in the horse: a new approach to testing of adrenal gland function. PMID- 6245612 TI - Bluetongue virus in bovine semen: viral isolation. AB - Vero cell cultures and embryonating chicken eggs were used for direct isolation of bluetongue virus from cattle blood and from semen samples. Cell culture and embryonating chicken eggs each were more effective than was the blood autograft inoculation of susceptible sheep with selected blood and semen samples. Evaluation of the cell culture technique indicated that the quality of the distilled water was the primary factor responsible for the increased sensitivity of the Vero cell cultures for the present blue-tongue viral isolations. Test results showed that urine was a poor specimen for viral isolation when assayed in chicken eggs. A comparison of tests for precipitating and complement-fixing antibodies to bluetongue virus indicated that the precipitin test was the more accurate of the two tests. PMID- 6245613 TI - [Cutaneous histiocytosarcoma: clinical, immunohistochemical and ultrastructural aspects; difficulties of study and problems of nosology (author's transl)]. AB - Reporting a case of cutaneous tumor of the back of recent occurrence and rapid increase in a 79-years-old woman, according to Crosti's "reticulosis", the authors discuss the following points:--the histiocytic nature of the tumor cells particularly based on immunohistochemical studies (peroxidase activity, anti-HTLA serum) and on electron microscopy with special reference to the multivesicular bodies found in their cytoplasm;--the tests for correct identification of the histiocyte (including electron microscopy, tests for HTLA and HBLA antigens, peroxidatic reaction, acid phosphatase activity, and in vivo or in vitro phagocytosis);--the out of date character of the concept of malignant "reticulosis" in the hematologica and dermatologic classifications, the recent advances in the knowledge of the nature of the so-called "reticulum" (or "reticular") cell which seems to be a distinct entity derived from the mesenchymal cell (as the fibroblast);--the clinical and evolutive characteristics of histiocytic tumors (no hematologic involvement, slow evolution, high radiosensitivity), the difficulties in defining their malignancy and, above all, in finding comparable references in the literature with complete cellular study;- the nosologic place of this affection among the group of haematodermas and in the pathology of the mononuclear phagocyte system. The generic term of cutaneous histiocytosarcoma (stage I or II) is suggested, including the whole malignant and isolated tumoral proliferations developing from the dermic histiocyte. PMID- 6245614 TI - Craniofacial synostosis in association with vitamin D--resistant rickets. AB - A patient with craniofacial synostosis and vitamin D--resistant rickets who underwent successful Le Fort II advancement is presented. The association of premature cranial synostosis with a variety of metabolic and hematological disorders is discussed. PMID- 6245615 TI - The use of cryosurgery in treating the fibrous papules of tuberous sclerosis. AB - A patient with fibrous papules of the face as a part of tuberous sclerosis was treated by cryosurgery. The definite improvement attending this treatment was maintained over an eighteen-month follow-up period. PMID- 6245616 TI - [Physiopathology of myasthenia gravis. A review (author's transl)]. PMID- 6245617 TI - [Neurophysiological monitoring of the myasthenia patient during and after thymectomy (author's transl)]. PMID- 6245618 TI - Sarcoid polyneuropathy: a histologically proved case. AB - A 58-year-old patient had subacute polyneuropathy. Electrophysiological studies showed inexcitability of the distal portion of the peroneal and posterior tibial nerves and minimal reduction in amplitude of the muscle potential with minimal slowing in motor nerve conduction velocity. The sural nerve biopsy showed multiple sarcoid granulomas in the epineurial and perineurial spaces, periangiitis and panangiitis, and axonal degeneration. Remarkable clinical improvement followed corticosteroid treatment. PMID- 6245619 TI - Mechanisms underlying epileptiform burst discharge. AB - Studies of hyperexcitable cells in alumina-gel and penicillin epileptogenic foci suggest that epileptid or triggered by a number of extrinsic factors which disrupt the normal depolarizing-hyperpolarizing balance. This paper presents the hypothesis that the most important influence for burst discharge is influx of calcium ions. This excitatory effect is modulated by synaptic inputs, hyperpolarizing conductances, cell morphology and membrane characteristics, and the extracellular milieu. The hypothesis incorporates findings from both penicillin and alumina models of epilepsy and provides experimentally testable concepts for further investigation. PMID- 6245620 TI - Pigmentation with doxorubicin therapy. PMID- 6245621 TI - Herpes zoster-varicella in cutaneous T-cell lymphomas. AB - The overall frequency of herpes zoster-varicella (HZV) infection in 221 patients with histologically confirmed cutaneous T-cell lymphoma was 10% (22 patients). The frequency of HZV infection and serious complications (viral dissemination, bacteremia) was relatively high in patients with evidence of extracutaneous involvement, especially in patients with Sezary syndrome. The major factors identified to account for this predisposition to HZV infection include intensive treatment with radiation therapy or drugs given for systemic effect and/or immunologic deficiency consequent to advanced disease. These observations are quite similar to those made in patients with Hodgkin's disease. PMID- 6245622 TI - Lymphocyte cyclic nucleotide and prostaglandin content in psoriasis: a preliminary report. AB - Lymphocytes from psoriatic patients were found to contain reduced levels of adenosine 3':5'-cyclic phosphate, guanosine 5'-cyclic phosphoric acid, and prostaglandin E, as compared with lymphocytes from normal subjects. The difference in prostaglandin F levels between psoriatic and control subjects was not statistically significant. These results could point to an immunologic defect in the immune system in psoriasis. PMID- 6245623 TI - The photodistribution of erythema multiforme. PMID- 6245624 TI - Interaction of N-(phosphonomethyl)glycine with some respiratory chain enzymes of isolated corn-shoot mitochondria. AB - Spectrophotometric measurements of the activities of some dehydrogenases and electron transfer complexes of isolated corn-shoot mitochondria revealed that N (phosphonomethyl)glycine (PMG), a broad-spectrum, non-selective, and post emergence herbicide, at a concentration of 6.25 x 10(-4)M enhanced by about 10% the activities of NAD+-linked malate and NAD+-linked isocitrate dehydrogenases. At concentrations of 5 x 10(-3)M and 10 x 10(-3)M PMG, the activities of succinate and the NAD+-linked dehydrogenases were reduced by at least 10% and 25%, respectively. Although no effect was observed on the activities of the electron transfer complexes at lower concentrations of PMG, these enzymes were inhibited by at least 10% and 20%, respectively, at 5.0 x 10(-3)M and 10 x 10( 3)M PMG. PMID- 6245625 TI - Surgical resection for benign and malignant liver disease. AB - The indications for major hepatic resections in 32 patients and the results are presented. Twelve right lobectomies, eight partial left lobectomies, five left lobectomies, four extended right lobectomies and three partial right lobectomies were performed with a 46% complication rate and an operative mortality rate of 12.5%. Ten primary liver cancers, 12 metastatic lesions, four hemangiomas and six "benign" lesions were removed. Of seven patients with hepatomas, four are alive at an average of 24 months postresection and three have no evidence of recurrence. Of 11 adult patients with metastatic lesions, six are alive at an average of 27 months postresection and three patients have no evidence of recurrence. All four patients with hemangioma are alive at an average of seven years. As in other series, our experience has increased with seven resections prior to 1970 and 25 since. Operative mortality has decreased in that period of time (42% to 4%); however, our complication rate in survivors has remained elevated (25% to 50%). Our experience agrees with others that cautious selection of patients for resection of malignant tumors of the liver can extend survival. PMID- 6245626 TI - The use of phenylmethylsulfonyl fluoride in the study of catabolite inactivation and repression in intact cells of Saccharomyces cervisiae. AB - Catabolite inactivation of fructose-1,6-bisphosphatase, isocitrate lyase, phosphoenolpruvate carboxykinase and malate dehydrogenase in intact cells could be prevented by phenylmethylsulfonyl fluoride added 40 min prior to the addition of glucose. Protein synthesis, fermentative and respiratory activity and catabolite repression were not affected. Elimination of catabolite inactivation by the addition of PMSF revealed that catabolite repression started at different times for different enzyme. PMID- 6245627 TI - Hepatitis B surface antigen in hepatocytes at necropsy. AB - Seventy cases of cirrhosis and hepatocellular carcinoma (HCC) and 43 cases with no primary liver disease were investigated at necropsy by Gomori's aldehyde fuchsin stain for the presence of hepatitis B surface antigen (HBsAg) in liver cells. The results were correlated with serum HBsAg levels determined by radioimmunoassay and hemagglutination tests performed during the last three months of life or after death. In more than 90% of cases, a correlation was found between the results in tissue and in sera. The aldehyde fuchsin stain is a reliable tool for the detection of HBsAg in patients with cirrhosis and with HCC or without primary liver disease. PMID- 6245628 TI - Ankylosing spondylitis in women. AB - Although ankylosing spondylitis (AS) has been considered rare in women, we believe that its incidence is underestimated. In our case studies of 12 women with AS the characteristic clinical features of the disease included onset before the age of 30 (12 patients); night pain and morning stiffness (12 patients); intermittent, migratory joint pain (9 patients); and history of uveitis (2 patients). Spine mobility was decreased in all patients. Sacroiliac (SI) (8 patients) and circumthoracic (5 patients) tenderness were common findings. If these pertinent clues are present, further diagnostic studies are indicated. Histocompatibility testing for the HLA-B27 antigen, which is reported to be present in over 90% of patients with AS, is useful in detecting early and mild forms of the disease. We found the antigen in 10 of 11 patients tested. Radioisotope (RI) scanning can show early inflammation of the SI joints long before changes are evident on standard roentgenograms: In 3 cases, SI films were reported as normal but RI scans revealed abnormal uptake and ratios. Early detection of AS prevents inappropriate treatment of patients and mislabeling them as functional complainers. PMID- 6245629 TI - Emg in vertebral Paget disease. PMID- 6245630 TI - Variation in the susceptibility of BHK populations and cloned cell lines to three strains of foot-and-mouth disease virus. AB - BHK monolayer and suspension cell populations maintained in different laboratories were found to vary in their susceptibility to infection with three strains of foot-and-mouth disease virus (FMDV). The susceptibility of parent cell populations was compared with that of individual clones of cells derived from them. The populations tested in this way consisted of a number of cell types, each expressing a different capacity to produce FMDV. The relative numbers of susceptible and insusceptible cells in each population appeared to determine the overall susceptibility of that population. The ability of the FMDV strain Asia 1 Iran 1/73 to multiply was an indicator of the general FMDV susceptibility of a BHK cell population. PMID- 6245631 TI - Primary monolayer culture of adult mouse hepatocytes -- a model for the study of hepatotropic viruses. AB - Primary monolayer cultures of adult mouse hepatocytes isolated by collagenase perfusion of the liver in situ were exposed to 2 hepatotropic viruses, an avian influenza A virus adapted to grow in mouse liver in vivo and a herpes simplex type I virus. Influenza virus infection led to lysis ofindividual hepatocytes and total monolayer destruction within 18 to 120 hours after infection according to the virus dose used. Virus replication was evidenced by assaying hepatocyte supernates for hemagglutinin and infectivity, by immunofluorescent staining and by electron microscopy. Herpes virus infection resulted in polykaryocyte formation followed by nuclear pycnosis and cell lysis. Virus replication was assayed by titration of supernate infectivity. PMID- 6245632 TI - Glycoproteins and sialyl transferase of human B lymphoblastoid cell lines. AB - We used two radiolabeling methods to study glycoproteins on the surface of lymphoblastoid cells. One of the methods affects tritiation of residues which are oxidized with galactose oxidase and the other causes tritiation of neuraminic acid residues. This approach was shown to allow a better resolution of cell surface glycoproteins than if either method were used alone. Glycoproteins of B1- 19 cells which harbor the Epstein-Barr virus genomes were compared with those of its parental cell line, BJAB, which does not harbor the viral genomes. These studies did not reveal a unique viral protein. A 28,000 mol. wt. glycoprotein was found to be the most prominent neuraminic acid-labeled product of B1--19 cells and also of the two other cell lines, Raji and Ly38, which harbor the EBV genomes. A similar molecular weight species from BJAB cells identified by galactose oxidase labeling might be deficient in neuraminic acid residues as it was poorly labeled by the periodate oxidation method. The neuraminic acid content and level of sialyl transferase of BJAB cells were found to be lower than those of the other cell lines studied. PMID- 6245635 TI - Pediatric solid tumors I: Wilms' tumor. PMID- 6245633 TI - Herpes simplex type 1 infection of nonpermissive rat XC cells. AB - Herpes simplex virus type 1 (HSV-1) infection of non permissive XC cells (a rat cell line transformed by Rous sarcoma virus) was studied. Using virus labeled with 3H-thymidine it was shown that adsorption is similar to that in a permissive system. By electron microscopy enveloped particles were observed in cytoplasmic vesicles in XC cells but not in the permissive system. However input viral DNA was degraded both in non permissive cells (XC) and permissive cells (HEp-2) and the degradation products were found incorporated into cellular DNA in the first case or into viral DNA in the second case. In the non permissive XC cells, it was possible to detect a small amount of incorporation of radioactive precursors into the viral DNA, identified by its buoyant density in CsCl of 1.726 g/cm3 and by hybridization with viral DNA. This DNA has the size of the native viral genome and its uptake of radioactive precursors was only partially inhibited by phosphonoacetic acid, a specific inhibitor of HSV-DNA polymerase. With permissive HEp-2 cells in the presence of such inhibitor, the obtained data are roughly the same as with XC cells, both in the presence or in the absence of phosphonoacetic acid. These results suggest that the observed viral DNA synthesis in XC cells is not a true replication but, further, a repair synthesis and, also, that the same events might take place in the permissive system before the onset of viral DNA replication. PMID- 6245634 TI - The polypeptides of human and mouse coronaviruses. Brief report. AB - The polypeptide compositions of two coronaviruses, human coronavirus strain 229E (HCV229E) and mouse hepatitis virus strain 3 (MHV3), were characterised on polyacrylamide gels. Similar polypeptide patterns were observed for both viruses consisting of large surface projection glycopolypeptides of mol. wt. 160,000 and 105,000 for HCV229E, and 170,000 and 90,000 for MHV3, two small polypeptides of mol. wt. varying from 24,000 to 20,000, and a polypeptide of mol. wt. 50,000. The results are discussed with respect to previous reports of the polypeptides of these and other coronaviruses. PMID- 6245636 TI - Granular cell myoblastoma involving the recurrent laryngeal nerve. AB - An unusual granular cell myoblastoma occurred surrounding the recurrent laryngeal nerve. Available information regarding the origin, biological behavior, and treatment of such tumors arising from the cervical trachea was reviewed. Frequently, the histologic features cause this lesion to be mistaken for a malignant tumor, and errors in diagnosis and treatment may be made. To our knowledge, encasement of a major motor nerve in the neck by a granular cell neoplasm has never before been reported. Since the overwhelming majority of these tumors behave in a benign fashion, we recommend that the surgeon attempt to spare functionally important nerves in rare instances when they are grossly surrounded by tumor. PMID- 6245637 TI - An analysis of some thermodynamic properties of iron-sulphur centres in site I of mitochondria. AB - 1. The midpoint potentials of the various iron-sulphur centres in Site I were determined at different pH values by the technique of redox potentiometry. An interesting feature is the pH-dependence of Centre N-2, the highest potential component of the NADH dehydrogenase segment of the respiratory chain. 2. The apparent midpoint potentials of Centre N-2 (NADH dehydrogenase) and S-1 (succinate dehydrogenase) and their pH-dependence was also determined by using the succinate/fumarate couple. Again Centre N-2 is pH-dependent in midpoint potential, and Centre S-1 is not. The results obtained by titrating with the succinate/fumarate couple are in quantitative agreement with those obtained for these centres by redox potentiometry. 3. Oxidation-reduction titrations of iron sulphur centres with the couple NADH/NAD+ and an analogue APADH/APAD+ in the presence of rotenone gave results substantially different from those obtained by redox potentiometry; these differences may be due to the mechanism of action of NADH dehydrogenase and its specific interaction with NADH. 5. The addition of ATP to an NAD+/NADH-poised system induces an uncoupler-sensitive oxidation of Centre N-4. PMID- 6245639 TI - A simple and fast method for the isolation of basolateral plasma membranes from rat small-intestinal epithelial cells. AB - A method was developed for the analytical and preparative isolation of basolateral plasma membranes from rat small intestine. They were separated on a self-orientating Percoll (modified colloidal silica) gradient starting with a heavy microsomal-membrane fraction and involving centrifugation at 48,000 g for 1 h. (Na+ + K+)-stimulated ATPase activity, used as a marker enzyme for the basolateral plasma membrane, is enriched 20-fold compared with that found in the homogenate of isolated intestinal epithelial cells. PMID- 6245638 TI - Non-esterified cholesterol-rich adrenal lipid fractions. Preparation, properties and preferential utilization for cholesterol side-chain cleavage by corticotropin stimulated adrenal mitochondria. AB - Rat adrenal 105,000 g supernatant contains two lipid moieties, 'lipid-I' and 'lipid-II' which contain non-esterified cholesterol and stimulate cholesterol side-chain cleavage in soluble or mitochondrial enzyme systems. Lipid-I contains relatively large low-density heat-stable particles, whereas lipid-II particles are smaller, more dense and heat-labile. Lipid-I and lipid-II can be separated from clear cytosol by ultracentrifugation and gel filtration respectively. Corticotropin plus cycloheximide treatment increases the non-esterified cholesterol concentrations in the lipid fractions, and stimulatory effects of lipids on cholesterol side-chain cleavage appear to correlate with non-esterified cholesterol concentrations therein. On addition of saturating amounts of cholesterol-rich lipid, pregnenolone synthesis and cholesterol binding to cytochrome P-450 are stimulated more in mitochondria from corticotropin stimulated adrenals than in mitochondria from control or corticotropin-plus cycloheximide-stimulated adrenals. These results support the contention that the corticotropin-induced increase in mitochondrial cholesterol side-chain cleavage involves an increase in cholesterol utilization as well as an increase in cholesterol availability. PMID- 6245640 TI - The mother-cell-membrane adenosine triphosphatase of sporulating Clostridium pasteurianum. AB - 1. Sporulation of Clostridium pasteurianum effects several changes in its proton translocating cell-membrane H(+)-ATPase. Notable among these are the acquisition of susceptibility to activation by trypsin and a changed protein subunit composition. 2. A protein was isolated from the mother-cell membrane that inhibited the ATP phosphohydrolase activity of purified vegetative-cell-membrane H(+)-ATPase [BF(0)F(1) complex, which consists of soluble ATPase (BF(1)) and the proton-channel component (BF(0))] and rendered it susceptible to trypsin activation. 3. This trypsin-sensitive inhibitor protein had a molecular weight of 10000 and on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis was indistinguishable from the novel protein subunit e of the mother-cell-membrane ATPase 4. In bacteriorhodopsin-containing everted membrane vesicles, the specific ATP synthetase activity of the mother-cell-membrane ATPase was significantly greater than that of the vegetative-cell-membrane ATPase. 5. Treatment with trypsin-sensitive inhibitor protein of artificial proteoliposomes containing bacteriorhodopsin and vegetative-cell-membrane H(+)-ATPase (BF(0)F(1)) significantly increased the specific ATP synthetase activity of this enzyme. 6. The ATP synthetase activity of crude cell-membrane preparations from cultures of Clostridium pasteurianum increased during that period in the course of sporulation when the membrane ATP phosphohydrolase was both most rapidly decreasing in specific activity and acquiring its susceptibility to activation by trypsin. PMID- 6245641 TI - Hormone-initiated maturation of rat liver mitochondria after birth. AB - 1. The injection of adrenaline, glucagon or cyclic AMP into foetal rats in utero initiates the maturation of energy transduction in rat liver mitochondria before birth. 2. The injection of the beta-blocker, propranolol, prevents this maturation process. 3. The maturation of mitochondrial energy transduction is measured in terms of the increase in the respiratory control index and mitochondrial adenine nucleotide concentration. 4. It is postulated that the actions of the hormones, acting through cyclic AMP, affect glycogenolysis and glycolysis to give rise to transient localized high concentrations of ATP. 5. It is the ATP that acts as the molecular trigger, effecting mitochondrial maturation. PMID- 6245642 TI - Subcellular distribution and movement of 5'-nucleotidase in rat cells. AB - 1. Cell-surface 5'-nucleotidase was assayed by incubating whole-cell suspensions with 5'[3H]-AMP in iso-osmotic buffer and measuring [3H]adenosine production. The activity of cell-surface 5'-nucleotidase in hepatocytes, adipocytes and lymphocytes isolated from the rat was 15.0, 0.5 and 0.8pmol/min per cell at 37 degrees C respectively. 2. Disruption of the cells by vigorous mechanical homogenization or detergent treatment exposed additional 5'-nucleotidase activity, which represented 52%, 25% and 21% of the total activity in the three cell types respectively. This increase in 5'-nucleotidase activity which occurred when the cells were homogenized was due to a second pool of 5'-nucleotidase within the cell, rather than activation of the cell-surface enzyme. 3. In hepatocytes the intracellular 5'-nucleotidase activity was membrane-bound, indistinguishable from cell-surface 5'-nucleotidase in its inhibition by rabbit anti-(rat liver 5'-nucleotidase) serum and its kinetics with AMP, and was located on the extracytoplasmic face of vesicles within the cell. 4. The cell-surface 5' nucleotidase of rat hepatocytes was rapidly inhibited when rabbit anti-(rat liver 5'-nucleotidase) serum or concanavalin A was added to the medium at 37 degrees C. Incubation with antiserum for 5 min at 37 degrees C inhibited 83 +/- 3% of the cell-surface enzyme. 5. Incubation of hepatocytes with exogenous antiserum or concanavalin A for 30 min at 37 degrees C resulted in over 50% inhibition of the intracellular enzyme. This inhibition was not prevented by disruption of the cytoskeleton or by ATP depletion. 6. Incubation of hepatocytes with exogenous antiserum or concanavalin A for up to 2h at 0 degrees C caused little or no inhibition of the intracellular enzyme, but over 75% inhibition of the cell surface enzyme. 7. When surface-inhibited hepatocytes were washed and resuspended in buffer at 37 degrees C, 5'-nucleotidase was observed to redistribute from the intracellular pool to the cell surface. PMID- 6245644 TI - Highly active immobilized hydrogenase from Desulfovibrio gigas. PMID- 6245643 TI - Protein degradation in hepatocyte monolayers. Effects of glucagon, adenosine 3':5'-cyclic monophosphate and insulin. AB - 1. Hepatocytes were isolated by collagenase perfusion of livers from fed rats and established in stationary monolayer culture. 2. Degradation of intracellular protein was measured in these monolayers after labelling for 16h with [3H]leucine followed by a 3h chase period in medium containing 2mM-leucine. 3. Proteolysis in this system was stimulated by physiological concentrations of glucagon and also by added dibutyryl cyclic AMP. The effects of these two agents were not additive, which is consistent with the view that they act by the same mechanism. 4. A close correlation was found between intracellular cyclic AMP concentrations generated by glucagon and the degree of stimulation of proteolysis elicited by the hormone. 5. Insulin reduced glucagon-stimulated proteolysis, but not glucagon-elevated intracellular cyclic AMP concentrations. 6. The continual presence of either insulin or glucagon was necessary for the full expression of their effects on proteolysis. 7. In the presence of cycloheximide, proteolysis was normally responsive to glucagon but not to insulin. In contrast, proteolysis was not responsive to either hormone in the presence of ammonia, an agent that blocks the final lysosomal step of protein breakdown. 8. We propose that in hepatocyte monolayers glucagon may act via cyclic AMP to increase cellular autophagy and thus increase proteolysis, whereas insulin inhibits these processes independently of cyclic AMP. PMID- 6245645 TI - Sequential assembly of newly synthesized histones on replicating SV40 DNA. PMID- 6245646 TI - Role of myo-inositol in the synthesis of phosphatidylglycerol and phosphatidylinositol in the lung. PMID- 6245647 TI - Isolation of a palmitoyl CoA-protein complex with properties of the ADP/ATP carrier from bovine heart mitochondria. PMID- 6245648 TI - Adrenomyeloneuropathy: increased accumulation of very long chain fatty acid in cultured skeletal muscle. PMID- 6245649 TI - Solubilization and chromatographic separation of gonadotropin receptor from adenylate cyclase in ovarian preparations. PMID- 6245650 TI - Extensive transcription of foreign DNA in a crown gall teratoma. PMID- 6245651 TI - Different chirality of the axial methionine in homologous cytochromes c determined by 1H NMR and CD sectroscopy. PMID- 6245652 TI - Involvement of cAMP-dependent protein kinase and pH on the regulation of cardiac sarcoplasmic reticulum. PMID- 6245653 TI - The effect of thyroid hormones and other kinetic modifiers on bisphosphoglyceromutase from human erythrocytes. PMID- 6245654 TI - Effects of indomethacin, 5,8,11,14-eicosatetraynoic acid, and p-bromophenacyl bromide on lysosomal enzyme release and superoxide anion generation by human polymorphonuclear leukocytes. PMID- 6245655 TI - Effects of adrenochrome on rat heart sarcolemmal ATPase activities. PMID- 6245656 TI - Ototoxicity of aminoglycosides correlated with their action on monomolecular films of polyphosphoinositides. PMID- 6245657 TI - Effects of low level administration of dichlorvos on adrenocorticotrophic hormone secretion, adrenal cholesteryl ester and steroid metabolism. PMID- 6245658 TI - Stimulation and inhibition of cyclic AMP formation in isolated rat fat cell by prostacyclin (PGI2). PMID- 6245659 TI - Activation of tryptophan hydroxylase from slices of rat brain stem incubates with N6, 02'-dibutyryl adenosine-3':5'-cyclic monophosphate. PMID- 6245660 TI - Induction of the synthesis of latent collagenase and latent neutral protease in chondrocytes by a factor synthesized by activated macrophages. PMID- 6245661 TI - Effect of oxygen-derived free radicals on hyaluronic acid. AB - To investigate possible mechanisms of hyaluronic acid depolymerization, superoxide anion and other secondary oxygen-derived free radicals were generated in vitro and allowed to act upon a hyaluronate substrate. Superoxide, generated either enzymatically with xanthine oxidase or by stimulation of polymorphonuclear leukocytes, reduced the viscosity of hyaluronate solutions dramatically while the chromatographic profiles of the glycosaminoglycan shifted toward lower molecular weights. Superoxide-treated hyaluronate also became susceptible to further degradation by beta-N-acetylglucosaminidase A. Experiments with scavengers of various toxic oxygen-derived free radicals clearly implicated these reactants as mediators of hyaluronate depolymerization. Generation of superoxide by leukocytes in vivo may account for the loss of synovial fluid viscosity that accompanies inflammatory joint disease. PMID- 6245662 TI - Inhibition of adenosine triphosphatases by gold. AB - Inhibition of adenosine triphosphatase (ATPase) by chlorauric acid (Au3+) and gold sodium thiomalate (Au+) was studied in dog brain and kidney and in human kidney enzyme preparations. Au3+ indiscriminately affected ouabain-sensitive (Na+ + K+-dependent) ATPase and ouabain-insensitive (Mg2+-dependent) ATPase with concentrations for 50% inhibition (I50) approximately 10(-6) M. The I50 of Au3+ for Na+ + K+ ATPase was several-fold higher in homogenates than in microsomal fractions. The enzyme was protected by bovine serum albumin. Although Au3+ and Au+ were equipotent against Mg2+ ATPase, Au+ inhibited Na+ + K+ ATPase 2 to 3 times more effectively than did Au3+. The inhibitory action of Au3+ (but not Au+) was potentiated by ascorbic acid, suggesting reduction of Au3+ to Au+ by ascorbic acid. The fractional inhibition of Na+ + K+ ATPase by Au3+ or Au+ was not affected by changing concentrations of NaCl, KCl, MgCl2, ATP, and MgATP. Decreasing pH from 8.0 to 6.8 enhanced both Au+ and Au3+ inhibition. We conclude that gold is one of the most potent nonspecific of Na+ + K+ ATPase, with characteristics differing from other metallic inhibitors of this enzyme system. PMID- 6245663 TI - Purification and properties of a collagenase inhibitor from cultures of bovine aorta. AB - Bovine medial explants in culture synthesize a potent inhibitor of mammalian collagenase but not of bacterial collagenase. This inhibitor has been partially purified and has an apparent molecular weight of 45,000. It is a glycoprotein and is stable to heat, trypsin, acid and mercurials. Inhibitory activity is destroyed on reductive alkylation. The inhibitor interacts with collagenase and this interaction leads to the loss of enzymatic activity. This inhibitor may play a physiological role in the control of collagen degradation in blood vessels. PMID- 6245664 TI - [Double immunodiffusion in seroepidemiology of Herpes simplex viruses]. PMID- 6245665 TI - [Seroepidemiology in the human species and in swine of the new strain of the porcine type]. PMID- 6245666 TI - [Influence of thyroid condition on 5'-nucleotidase activity of the plasma membrane in the rat liver]. AB - The effect of thyroid hormones on the Kinetic properties of plasmatic membrane 5' nucleotidase in rat liver is studied. The Vmax and Km which increased significatively a week after thyroidectomy were reported to the normal values by the chronic administration of T3. The decrease in Vmax and Km observed five weeks after thyroid ablation may be attributed to secondary effects occurring with time. PMID- 6245667 TI - [Influence of age on the 5'-nucleotidase activity of the plasma membrane of rat liver: note II]. AB - The effect of age on the kinetic properties of the plasma membrane 5' nucleotidase in liver cells is studied. Vmax and Km and the discontinuity temperature are lower in the 230 +/- 15 days old rats. It appears that lipids do not affect the isotermic kinetic of the enzyme, while the decrease in the discontinuity temperature in the 230 +/- 15 days old animals might be related to the higher percent of insaturated fatty acids. PMID- 6245668 TI - [Fabry's disease with malocclusion and acromegalic-appearance: clinical and electromicroscopic studies (author's transl)]. AB - The present case is a 24-years-old man who complained painful attack with numbness in both bilateral shoulder regions and distal extremities. This pain was increased by the stimulations of sunlight and heat. On physical examinations, he had an acromegalic-like-appearance, thick mustache and beard. Malocclusion of the teeth which showed the broad space was found. And skin lesion was not found out. Hypesthesia in bilateral distal extremities was revealed and no other abnormal neurological findings were observed. He was made diagnosis of Fabry's disease by laboratory examinations which were alpha-galactosidase deficiency analysed in leukocytes, increased ceramide trihexosides demonstrated in urinary sediment and electron microscopic findings in the biopsy of the skin and sural nerve. His mother had and decreased alpha-galactosidase activity which levels showed between normal and patient and was speculated to be a carrier. On an electron microscopy, "Zebra body" was observed in fibroblasts, capillary endothelial cells, their pericytes, prineural and Schwann cells. Many of them had a distinct limiting membrane and laminal structure with irregular alterations of light and dark zone. In the cytoplasma of Schwann cells, there were many rough endoplasmic reticulums which were located parallel with alignment and seemed to show the loosed laminal structure with the unclear limited membrane. Occasionally, fusions between irregular laminal structure and rough endoplasmic reticulum were also observed. These findings could be indicated that the formation of Zebra body is related to rough endoplasmic reticulum, because laminal structure which described above is corresponded to pre-Zebra body. In the cytoplasma of the prineural cells, recket like structure which was seen in histiocytosis X were occasionally observed. PMID- 6245669 TI - The nature of gentamicin-induced neuromuscular block. AB - Gentamicin in concentrations of 0.05--0.2 mmol litre-1 blocked neuromuscular transmission in the toad sartorius nerve--muscle preparation by decreasing the release of transmitter. In concetnrations of 0.5--1 mmol litre-1 it decreased the amplitude of the miniature end-plate current by a curare-like action, without affecting the mean open channel lifetime. PMID- 6245670 TI - The toad in the hole: an hypothesis to explain the action of anaesthetics. PMID- 6245671 TI - ESR investigation of paraffin-embedded ocular melanomas. AB - Ocular melanomas embedded in paraffin wax for histological examination have been studied by electron spin resonance (ESR) spectroscopy. A free-radical signal was detected at the g = 2.003 section of the spectrum. The amplitude of this signal was correlated with the number of melanin granules in microscopical slides made from the tumour. This positive correlation can make ESR spectroscopy suitable for estimating the melanin content in the embedded melanoma blocks. Additional paramagnetic signals can also be detected. The clarification of their significance needs, however, further ESR measurements. PMID- 6245672 TI - Selective macrophage inhibition abolishes warfarin-induced reduction of metastasis. PMID- 6245673 TI - The ether lipid tumour marker in human liver with hepatocellular carcinoma. PMID- 6245674 TI - Immune reactions in epidermodysplasia verruciformis. AB - Serum antibodies against human papilloma virus have been measured using immunodiffusion and enzyme linked immunosorbent assay in twelve patients with epidermodysplasia verruciformis (EV). The results were compared with those from sixty-six patients with other types of human papilloma virus diseases. Antibody prevalences were slightly lower in patients with EV than in the control patients. More remarkable was the difference between EV patiens and control subjects in tests of non-specific cell-mediated immunity, which was markedly depressed in the majority of patients with EV, but in the main preserved in patients with common warts. No specific immunological parameter was shown to be associated with malignant conversion of EV lesions, but malignancy was linked to the character of the inducing virus, and particularly to HPV type 5. PMID- 6245675 TI - The effect of dietary fibre on bile acid metabolism in rats. AB - 1. Forty-eight male rats were fed sequentially for 14 d periods on diets containing different fibre contents. 2. One of the high-fibre diets was a commercial pelleted diet. The other was a low-fibre diet supplemented with 200 g wheat bran/kg. 3. At the end of each feeding period eight rats were killed. Liver microsomal cholesterol 7 alpha-hydroxylase (EC 1.14.1.-) activity and bile acid content of small intestine and colon were determined. 4. The different diets did not significantly alter the total intestinal bile acids, but affected the distribution and qualitative pattern in the colon and small intestine. 5. On the high-fibre diets deoxycholate, and hyodeoxycholate tended to be increased. 6. On the low-fibre diets the alpha, beta- and omega-muricholic acids tended to be increased. 7. Liver microsomal cholesterol 7 alpha-hydroxylase activity was lower in rats on the low-fibre and bran-supplemented low-fibre diets compared with that in rats fed on the commercial pelleted diet. PMID- 6245676 TI - Motor activity in the large intestine of the pig related to dietary fibre and retention time. PMID- 6245677 TI - Promoter melting by T7 ribonucleic acid polymerase as detected by single-stranded endonuclease digestion. PMID- 6245678 TI - Involvement of lysines-72 and -79 in the alkaline isomerization of horse heart ferricytochrome c. AB - Spectrophotometric titrations of five singly modified horse heart ferricytochromes c, specifically (trifluoromethyl)phenylcarbamylated (CF3PhNHCO-) or trifluoroacetylated (CF3CO-) at lysines-13, -72, and -79, were carried out. The CF3PhNHCO-Lys-13, Lys-79, and CF3CO-Lys-79 derivatives all underwent alkaline isomerization with loss of the 695-nm band to low-spin species with an apparent pK of about 8.9, as did the unmodified cytochrome. However, modification of lysine-72 appeared to alter the reaction pathway since the CF3PhNHCO-Lys-72 derivative isomerized to a high-spin form with an apparent pK of 9.3, while the CF3CO-Lys-72 derivative isomerized to a low-spin species with an apparent pK of 9.6, indicating that lysine-72 may be the normal sixth iron ligand in the native protein alkaline isomer. These results, together with those of other workers, suggest a model for the alkaline transition in which replacement of the methionine iron ligand is dependent on a number of factors, including the local availability and relative affinities of possible ligands for the heme iron and the effects of ionic and hydrophobic interactions on the tertiary structure of the molecule. PMID- 6245679 TI - Na+,K+-ATPase: ligand-induced conformational transitions and alterations in subunit interactions evidenced by cross-linking studies. PMID- 6245680 TI - Vitamin K dependent carboxylase: subcellular location of the carboxylase and enzymes involved in vitamin K metabolism in rat liver. AB - Vitamin K dependent carboxylation of an exogenous peptide substrate and endogenous protein substrates, vitamin K epoxidation, and reduction of vitamin K epoxide were measured in subcellular fractions from rat liver. The rough microsomal fraction was highly enriched in all four activities; lower levels were found in smooth microsomes. Mitochondria, nuclei, and cytosol had negligible activities. The addition of 0.2% Triton X-100 to intact microsomes resulted in a 10-20-fold stimulation in carboxylation of a peptide substrate. This marked latency suggests that the active site of the carboxylase may be accessible only from the lumen of the microsomal membrane. A lumen-facing orientation of the carboxylase was also supported by its inaccessibility to trypsin in intact microsomes contrasted with marked inhibition by trypsin in detergent permeabilized microsomes. Vitamin K epoxidase and epoxide reductase activities were also inhibited by trypsin much more effectively in permeabilized than in intact microsomes, although some degree of exposure at the cytosolic surface was also indicated. These data suggest that carboxylation is an early event in prothrombin synthesis occurring primarily on the lumen side of the rough endoplasmic reticulum membrane. The location of the vitamin K epoxidation reduction cycle enzymes is consistent with their possible role in the carboxylation reaction. PMID- 6245681 TI - Characterization of the ribulosebisphosphate carboxylase-carbon dioxide-divalent cation-carboxypentitol bisphosphate complex. AB - Ribulosebisphosphate carboxylase forms a stable quaternary complex with CO2, divalent cation, and carboxypentitol bisphosphate. Incorporation of nonexchangeable CO2 into the complex requires the presence of a divalent cation. MG2+, Mn2+, or Co2+ supports stoichiometric binding of CO2 activator. When the quaternary complex is formed in the presence of saturating CO2, stoichiometric amounts of cation are bound in a nonexchangeable fashion. Incorporation of Mn2+ into an enzyme-CO2-Mn2+-carboxypentitol bisphosphate complex permitted investigation of cation environment by electron spin resonance (ESR) techniques. Measurements at 9 and 35 GHz suggest rhombic distortion of the coordination sphere of bound Mn2+. A complex inner sphere liganding of the cation bound in the quaternary complex would account for both the ESR spectra and the marked stability of the complex with respect to cation exchange. PMID- 6245682 TI - Escherichia coli elongation factor G blocks stringent factor. AB - The relationship between the binding domains of elongation factor G(EF-G) and stringent factor (SF) on ribosomes was studied. The binding of highly purified, radioactively labeled, protein factors to ribosomes was monitored with a column system. The data show that binding of EF-G to ribosomes in the presence of fusidic acid and GDP or of the noncleavable analogue GDPCP prevents subsequent binding of SF to ribosomes. In addition, stabilization of the EF-G-ribosome complex by fusidic acid inhibits SF's enzymatic activities. Removal of protein L7/L12 from ribosomes leads to weaker binding of EF-G, while SF's binding and activity are unaffected. In the absence of L7/L12, EF-G-dependent inhibition of SF binding and function is reduced. The data presented in this report suggest that these two factors bind at overlapping, or at least interacting, ribosomal domains. PMID- 6245683 TI - A potentiometric and kinetic study on the respiratory chain of ferrous-iron-grown Thiobacillus ferrooxidans. AB - The type and number of respiratory chain components present in membranes of Thiobacillus ferrooxidans have been investigated. These redox components were resolved potentiometrically and kinetically. Using optical techniques two cytochromes a1, multiple cytochromes c and two cytochromes b were detected. By using electron paramagnetic resonance, two copper-containing centres, high and low spin ferric haems and a ferredoxin centre were detected. Based on the combination of a potentiometric resolution and a kinetic study a model for the sequence of the respiratory chain components in the Fe2+ to O2 branch of the T. ferrooxidans respiratory chain is proposed. PMID- 6245684 TI - Oxidative phosphorylation and ATPase activities of human tumor mitochondria. AB - Studies were carried out with intact mitochondria isolated from human astrocytoma, oat cell carcinoma and melanoma which were propagated in athymic mice. These human tumor mitochondria were capable of coupled oxidative phosphorylation. They also showed significant uncoupler-stimulated ATPase if defatted bovine serum albumin was included in the assay media. However, the uncoupler response curves were different and the magnitude of the ATPase activity was lower than could be obtained with mitochondria of a normal tissue, such as liver. Some of these characteristics were also exhibited by mitochondria from several animal hepatomas and Ehrlich ascites tumor. In the three tumors studied, mitochondria from oat cell carcinoma were more labile, whereas higher respiratory control ratios and greater stimulation of ATPase by uncouplers were obtained with melanoma mitochondria. The mitochondrial ATPase was not the major cellular ATPase in any of the three tumors. This was indicated by a low inhibition of the ATPase activity of tumor cell homogenates by oligomycin. A very large fraction of the cellular ATPase activities was recovered in the microsomal fractions. PMID- 6245685 TI - Isolation and characterization of soluble cytochrome c-553 and membrane-bound cytochrome f-553 from thylakoids of the green alga Scenedesmus acutus. AB - Soluble cytochrome c-553 and membrane-bound cytochrome f-553 from the alga Scenedesmus acutus were purified to apparent homogeneity. The properties of cytochrome c-553 are comparable to preparations obtained from other eukaryotic algae, whereas the thylakoid-bound species resembles higher plant cytochrome f. Common characteristics are: 1. An asymmetrical alpha-band at 553 nm. 2. A midpoint redox potential of +38 MV (pH 7.0), with a pH dependency above pH 8.0 of -60mV/pH unit. 3. Formation of a pyridine hemochromogen with a maximum at 550 nm; no adducts with CN- or CO are observed. Distinguishing features are: 1. Cytochrome f-553 has a more complicated beta-band, with maxima at 531.5 and 524 nm, and hence a more complex low-temperature spectrum. Also the positions of the gamma- and delta-bank at 421.5 and 331 nm, respectively, distinguish cytochrome f 553 from cytochrome c-553, with gamma- and delta-bands at 416 and 318 nm. 2. The ferricytochrome c-553 spectrum exhibits a weak band at 692 nm, which is not observed with cytochrome f. PMID- 6245686 TI - pH dependence of the redox potential of Pseudomonas aeruginosa cytochrome c-551. AB - The redox potential of Ps. aeruginosa cytochrome c-551 varies with pH between pH 5 and 8. The pH dependence can be analysed in terms of a pKa of 6.2 in the oxidised form and a pKa of 7.3 in the reduced form. The same pKa values are also observed in NMR spectra of the two oxidation states and the pKa of 7.3 is observed in titration of the visible absorption spectrum of the ferrocytochrome. From the NMR studies these pKa values have been assigned to the ionisation of one of the haem propionic acid groups. pH dependence of redox potential is of variable occurrence among cytochromes and the possible significance and basis of this variation is discussed. PMID- 6245687 TI - Studies on (Na+ + K+)-activated ATPase. XLIV. Single phosphate incorporation during dual phosphorylation by inorganic phosphate and adenosine triphosphate. AB - (Na+ + K+)-ATPase can be phosphorylated by its substrate ATP as well as by its product inorganic phosphate. The maximal capacity for phosphorylation by either of these two substances is one mol phosphate per mol enzyme. In order to investigate whether the enzyme molecule possesses only on phosphorylation site common to ATP and Pi, or two phosphorylation sites, one for ATP and one for Pi, dual phosphorylation of the enzyme has been carried out. Under conditions, which are maximally favourable for each type of phosphorylation, successive phosphorylation by Pi and ATP leads to a maximal incorporation of only one mol phosphate per mol enzyme. The phosphorylation capacity for ATP decreases by the same amount as the Pi-phosphorylation level increases, without an effect on the apparent affinity for ATP. The results can be explained by assuming either a single common phosphorylation site for Pi and ATP, or a conformational change of the enzyme following phosphorylation by Pi, which excludes phosphorylation by ATP. PMID- 6245688 TI - Sugar uptake by intestinal basolateral membrane vesicles. AB - A high yield of membrane vesicles was prepared from the basolateral surface of rat intestinal cells using an N2 cavitation bomb and density gradient centrifugation. The membranes were enriched 10-fold and were free of significatn contamination by brush border membranes and mitochondria. The rate of D E114C]glucose and L-E13H]glucose uptake into the vesicle was measured using a rapid filtration technique. D-Glucose equilibrated within the vesicles with a half-time 1/25th that for L-glucose. The stereospecific uptake exhibited saturation kinetics with a Km of approx. 44 mM and a V of approx. 110 nmol . mg-1 min-1 at 10 degrees C. The activation energy for the process was 14 kcal . mol-1 below 15 degrees C and it approached 3 kcal . mol-1 above 22 degrees C. Carrier mediated uptake was eliminated in the presence of 1 mM HgCl2 and 0.5 mM phloretin. The rate of transport was unaffected by the absence or presence of sodium concentration gradients. Competition studies demonstrated that all sugars with the D-glucose pyranose ring chair conformation shared the transport system, and that, with the possible exception of the -OH group at carbon No. 1, there were no specific requirements for an equatorial -OH group at any position in the pyranose ring. In the case of alpha-methyl-D-glucoside its inability to share the D-glucose transport system may be due to steric hindrance posed by the -OCH3 group rather than by a specific requirement for a free hydroxyl group at the position in the ring. It is concluded that sugars are transported across the basolateral membrane of the intestinal epithelium by a facilitated diffusion system reminiscent of that in human red blood cells. PMID- 6245689 TI - Lateral mobility of beta-receptors involved in adenylate cyclase activation. AB - Cationized ferritin was found to inhibit the lateral mobility of intramembrane proteins in turkey erythrocyte membranes and the activation of adenylate cyclase by the (--)-epinephrine-bound beta-adrenergic receptor. It was observed that cationized ferritin has only a small direct effect on the beta-receptor and on the adenylate cyclase moiety. It is concluded that the cationized ferritin induced inhibition of the hormone-dependent cyclase activity results from the inhibition of the lateral mobility of the receptor and therefore a decrease in the bimolecular rate of interaction between the receptor and the enzyme. PMID- 6245690 TI - Plasma membrane changes associated with rat liver regeneration. AB - The lipid composition and fluidity of plasma membranes have been studied at different stages of liver regeneration (4, 15 and 24 h after surgery). The phospholipid and fatty acid composition is not modified, whereas the cholesterol/phospholipid ratio is lower with respect to control membranes. The modification of the physical properties of the membranes has been studied directly by EPR analysis and indirectly by temperature dependence and cooperativity of some membrane-bound enzymes (Mg2+-ATPase, (Na+ + K+)-ATPase and 5'nucleotidase). Surgical operation or anaesthesia alone causes an early increase in fluidity; such an effect appears to be markedly reduced at a later stage. There seems to be a marked effect of regeneration on plasma membrane fluidity 15 h after partial hepatectomy when several parameters--surface fluidity, cholesterol/phospholipid ratio, and 5'-nucleotidase activity in the presence of concanavalin A -- are modified and indicate an increase in membrane fluidity. It is suggested that this modification of membrane properties could be related to the proliferative process. PMID- 6245691 TI - Effect of calcium, insulin and growth hormone on membrane fluidity. A spin label study of rat adipocyte and human erythrocyte ghosts. AB - ESR spectra were recorded from rat epididymal adipocyte ghosts labeled with the 5 nitroxide stearic acid spin probe, I(12,3). Polarity-corrected and approximate order parameters, that are sensitive to the flexibility of the incorporated label, were used to evaluate the membrane lipid fluidity. Addition of CaCl2 a 37 degrees C decreased the fluidity, as indicated by positive increases in the order parameters. The ordering effect of Ca2+ was concentration-dependent, reached saturation at approx. 3--4 mM, and was completely reversed by excess EGTA. Previous studies indicated that low- and high-affinity sites on adipocyte plasma membranes are able to bind 45Ca2+, and our results suggest that Ca2+-induced alterations in the lipid fluidity involve cation binding to low-affinity sites. The cellular movements of Ca2+ and, in particular, the binding of Ca2+ to the plasma membrane may play important roles in insulin's action on fat cell function. The possibility that insulin directly alters the membrane fluidity was tested by adding hormone to freshly-prepared I(12,3)-labeled adipocyte ghosts. Insulin, at concentrations (10(-6) M) that enhance glucose uptake into intact adipocytes, did not affect the fluidity of ghosts suspended in buffers with or without Ca2+. The fluidities of I(12,3)-labeled rat adipocyte ghosts or human erythrocyte ghosts were also unaffected by various forms of human growth hormone. PMID- 6245692 TI - Defective conformational response in a selectively trypsinized (Na+ + K+)-ATPase studied with tryptophan fluorescence. AB - 1. Monitoring protein conformations of purified (Na+ + K+)-ATPase with intrinsic fluorescence we have examined if altered conformational responses accompany the defective catalytic and transport processes in selectively modified 'invalid' (Na+ + K+)-ATPase which is obtained by graded tryptic digestion of the Na+ form of the protein. 2. The protein fluorescence intensity of the K+ form (E2K) of both control and invalid (Na+ + K+)-ATPase is 2--3% higher than that of the Na+ form (E1Na). By varying the NaCl concentration we found evidence for different fluorescence intensities of the two phosphoenzymes; E2P has the same fluorescence intensity as E2K and the intensity of E1P is similar to that of E1Na. The fraction of phosphoenzyme present as E2P can therefore be determined as the amplitude of the fluorescence change accompanying phosphorylation in the absence of K+ divided by the amplitude of the full response to K+. 3. Titration of the fluorescence responses of the invalid (Na+ + K+)-ATPase shows that the tryptic split alters the noise of the equilibria between the cation-bound conformations, E1Na and E2K, and between the phosphoforms, E1P and E2P, in the direction of the E1 forms. 4. Vanadate binds to the Mg2+-bound form of E2K and prevents further changes in fluorescence intensity of the protein. The conformative responses of invalid (Na+ + K+)-ATPase are insensitive to vanadate in agreement with the reduced vanadate binding affinity of this enzyme. 5. The defective conformative response of the invalid (Na+ + K+)-ATPase in relation to its catalytic defects, reduced Na+ transport, and insensitivity to vanadate suggest that the transitions between Na+ forms (E1) and K+ forms (E2) of the protein are coupled to the catalytic and transport reactions of the (Na+ + K+)-pump. PMID- 6245694 TI - Phenobarbital induces slow recovery from sodium inactivation at the nodal membrane. AB - Voltage-clamp experiments were performed on single myelinated nerve fibres of Rana esculenta at 20 degrees C in Ringer's solution and in solutions containing phenobarbital-sodium ([PB] less than or equal to 5 mM). The reduction of the sodium current under phenobarbital could be explained by an increase in the resting sodium inactivation; h infinity (E) was shifted towards more negative membrane potentials. The recovery from sodium inactivation proceeded with two time constants. The fast process could be described with the same time constant as in Ringer's solution, whereas the slow process had a time constant approx. 40 times larger. The slow process was also potential-dependent and could be described by 1/(0.025 alpha h + beta h), where alpha h and beta h denoted the rate constants in Ringer's solution. With the measured blockage of sodium channels by phenobarbital, both the shift of h infinity (E) and the slow recovery from sodium inactivation could be explained. PMID- 6245693 TI - Studies on (K+ + H+)-ATPase. I. Essential arginine residue in its substrate binding center. AB - 1. A membrane vesicle fraction containing a high (K+ + H+)-ATPase activity was isolated from porcine gastric mucosa. The enzyme has a pH optimum of 7.0 and is stimulated by T1+, K+, Rb+ and NH4+ with KA values of 0.13, 2.7, 7.6 and 26 mM, respectively, at this pH. 2. Incubation of the isolated membrane fraction with butanedione leads to inactivation of the (K+ + H+)-ATPase activity. The pH dependence of the (K+ + H+)-ATPase activity. The pH-dependence of the inactivation and the reversibility of the reaction, observed after removal of excess butanedione and borate, indicate that modification of arginine is involved. 3. The inactivation of (K+ + H+)-ATPase activity by butanedione is time dependent and follows second-order kinetics. From the dependence of the inactivation rate on the reagent concentration it appears that a single arginine residue is involved in the inactivation of the (K+ + H+)-ATPase activity. 4. ATP, deoxy-ATP, ADP and adenylyl imidodiphosphate (AMPPNP), but not CTP, GTP and ITP which are poor substrates, protect the enzyme against butanedione inactivation, suggesting that the essential arginine residue is located in the ATP binding centre. 5. In the presence of Mg2+ the butanedione inactivation is increased, and the protection by ATP, deoxy-ATP and ADP (but not that by AMPPNP) is less pronounced. This suggests that Mg2+ induces a conformational change in the enzyme, exposing the arginine group and coinciding with phosphorylation and subsequent release of ADP from its binding site. PMID- 6245696 TI - Further analysis of the type differences of rat-liver mitochondrial DNA. AB - 1. The sequence of the small Hind III fragment F of rat-liver mitochondrial DNA (mtDNA) type A and type B was determined in order to investigate the nature of the differences between the two types of mtDNA and to determine its position in the Hind III fragment map. 2. The three differences found were point mutations. No deletion or insertion and no modification was observed. Two of the three differences affect the sequences which are recognition sites for Eco RI, Alu I and Taq I in type A, but not in type B, mtDNA. 3. The presence of an Eco RI restriction site only within the Hind III fragment F of type A shows that the fragment is situated in between the Hind III fragments A and E. 4. In one of the six reading frames, the Hind III fragment F contains the code for a carboxyl terminal end of a polypeptide in which the three mutations do not lead to alterations in the possible aminoacid sequence. 5. The restriction sites for Taq I and a number of the sites for Alu I and Hae III were mapped. 6. The positions of the Hap II fragment J, and of a Hind III fragment G on the mtDNA were determined. PMID- 6245695 TI - Size characteristics of the solubilized sodium channel saxitoxin binding site from mammalian sarcolemma. AB - The sodium channel saxitoxin binding component from rat sarcolemma was solubilized with medium chain length non-ionic detergents including NP-40, Brij 96 and Lubrol-PX. Phospholipid was required for stability of the binding component. Specific saxitoxin binding was significantly temperature sensitive even with optimal levels of phospholipid present. The solubilized saxitoxin binding component chromatographed on Sepharose 6B at a position corresponding to that of a globular protein of 95--10 A Stokes radius, but had an apparent s20,w typical of a smaller molecule (s20,w = 9.2--10). Column behavior and s20,w were independent of the specific detergent used for solubilization. Anomalous column behavior may reflect molecular asymmetry, contribution from bound detergent or similar considerations. PMID- 6245697 TI - Reaction of T7 DNA with a polycyclic aromatic hydrocarbon. Lack of structural perturbation. AB - Bacteriophage T7 DNA reacts uniformly with trans-7,8-dihydroxy-anti-9,10-epoxy 7,8,9,10-tetrahydrobenzo(a)pyrene(anti-BPDE). The reaction product retains the native configuration so that only one site sensitive to S1 nuclease is produced for every 70 anti-BPDE adducts. DNA treated with anti-BPDE is retained on benzoylated naphthoylated DEAE-cellulose even after washing with 1.0 M salt solutions. About 100 adducts per T7 molecule are required for adherence which is not due to breaks or single-stranded regions since adherence is not affected by S1 nuclease treatment. The binding of anti-BPDE reacted DNA to benzoylated naphthoylated DEAE-cellulose is cooperative and requires many residues per bound fragment. Treatment of T7 DNA treated with anti-BPDE with restriction endonuclease yields smaller molecules, still containing adducts, which do not adhere. We interpret these results to mean that reaction with BPDE does not involve deformation of the DNA structure and that the adducts lie in a position which they are readily accessible for interaction with aromatic groups on the column resin. PMID- 6245698 TI - Analysis of highly repeated DNA sequences of rat with EcoR1 endonuclease. AB - Cleavage of rat liver nuclear DNA with EcolR1 restriction endonuclease yields 14 discrete fragments ranging from 2300 to 93 base pairs in length, representing approx. 10.5% of the rat genome. Fragments of 1500, 180, and 93 base pairs are reiterated over 100 000 times; fragments of 2300, 880, 290, and 200 base pairs are reiterated over 20 000 times; the remaining fragments are present in over 1000 copies per genome. When compared to whole rate DNA, 11 were 1-5% richer in A . T base pairs and five were 1.5-2.5 times more methylated. From the criteria of the banding patterns in complete and incomplete digests, base composition and extent of methylation, none of these fragments appeared to be generated as oligomers of a basic shorter repeat. The reassociation of EcoR1 fragments was monitored on hydroxyapatite and by S1 nuclease treatment in order to assess band reiteration frequency and the possibility of interpersion or short internal repeats. The renaturation of the four smallest EcoR1 fragments gave no indication of short internal repeats from hyperpolymer formation nor interpersion with lower frequency sequences by size reduction after S1 nuclease treatment. Anomalous renaturation of several large fragments was observed, possibly due to internal repeats. PMID- 6245699 TI - Pyrophosphate analogues as inhibitors of herpes simplex virus type 1 DNA polymerase. AB - Twenty nine pyrophosphate analogues have been tested for their ability to inhibit herpes simplex virus type 1 (HSV-1) DNA polymerase activity. The structural requirements for active inhibitors and their mechanism of action have been investigated. Active compounds had two negatively charged groups at close proximity. The most active compounds contained free phosphono and/or carboxyl groups. Apart from phosphonoformate and phosphonoacetate, which were strong inhibitors, some other analogues, 2-phosphonopropionate, 2 phenylphosphonoacetate, oxalate, carbonyldiphosphate, methanehydroxy diphosphonate and hypophosphate also inhibited the HSV-1 DNA polymerase activity. With the exception of hypophosphate the tested compounds inhibited the activity of calf thymus DNA polymerase alpha to a lesser extent than the activity of the HSV-1 DNA polymerase. All inhibitors gave linear uncompetitive inhibition of HSV 1 DNA polymerase with activated DNA as variable substrate. With the four deoxynucleoside triphosphates as variable substrates all inhibitors except hypophosphate gave linear non-competitive inhibition patterns. Hypophosphate caused a more competitive type of inhibition. The inhibition constants for the active compounds have been determined. Phosphonoformate, phosphonoacetate, methanehydroxydiphosphonate and hypophosphate also inhibited HSV-1 plaque formation in cell culture. PMID- 6245700 TI - Maxi-circles and mini-circles in kinetoplast DNA from trypanosoma cruzi. AB - Maxi-circles are a minor component of kinetoplast DNAs from all trypanosomatids studied, but they have not previously been found in Trypanosoma cruzi; We have spread intact kinetoplast DNA from the epimastigotes of strain Y in protein monolayers and analysed the mini-circle networks by electron microscopy. Long loops up to 10 micrometer were present, extending from the network rim; these are considered typical of maxi-circles. The presence of maxi-circles was proven by digestion of kinetoplast DNA with restriction endonucleases and S1 nuclease. This released a minor DNA component, detectable by agarose gel electrophoresis, which hybridized to maxi-circle DNA from Trypanosoma brucei. The molecular weight of the linearized maxi-circle of Trypanosoma cruzi is 26 . 10(6), as judged from its electrophoretic mobility in 0.6% agarose. Our restriction enzyme analysis of the mini-circles of Trypanosoma cruzi has confirmed their sequence heterogeneity and internally-repeated structure. We have found that more than 90% of the mini circles are cut into 1/4 length molecules by endonuclease TaqI. Denaturation and renaturation of mini-circles, cut once with endonuclease MboI, mainly yields linear and circular molecules with single-stranded eyes and tails in electron micrographs. This shows that 1/4 repeats contain sub-segments in which sequence divergence is extensive. Our EcoRI and HapII digests differ in fragment size distribution from those previously reported. This suggests that this distribution may not be a stable characteristic of the Y strain. PMID- 6245701 TI - Magnetic circular dichroism study of the binding of netropsin and distamycin A with DNA. AB - The magnetic circular dichroism (MCD) of netropsin and distamycin-A is reported. New data for the interaction with dA ; dT base pairs in DNA were obtained from the MCD of their complexes with DNA duplex polymers. The MCD results allow an interpretation of the induced Cotton effects in the natural CD spectra of netropsin and distamycin-A complexes with DNA. While large distortions of the bases in DNA by the oligopeptide interaction is excluded, some subtle conformational variations of the DNA might explain the inhibition of the enzyme function of netropsin and distamycin-A on DNA. PMID- 6245702 TI - Fractionation of native and reconstituted chromatin by digesting with deoxyribonuclease ii. AB - Native and reconstituted chromatin from Ehrlich ascites tumor cells were fractionated into template-active and inactive fractions by the DNAase II/Mg2+ solubility method of Gottesfeld et al. (Gottesfeld, J.M., Garrard, W.T., Bagi, G., Wilson, R.F. and Bonner, J. (1974) Proc. Natl. Acad. Sci. U.S.A. 71, 2193 2197). The Mg2+-soluble (template-active) fractions were compared in respect to sedimentation behavior in sucrose gradients and the relative content of specific transcribed (ribosomal) and non-transcribed (satellite) DNA sequences. It was found that the Mg2+-soluble fraction of the native chromatin was enriched in ribosomal DNA while almost completely devoid of satellite DNA; the nucleoprotein monomer of this fraction sedimented in sucrose gradient at 14 S. Similar-results were obtained if chromatin was fractionated in the presence of 3 M urea. With reconstituted chromatin, however, neither the sedimentation profile, nor the relative content of ribosomal and satellite DNA sequences were recovered, thus indicating that reconstitution did not yield nucleoprotein structurally similar to native chromatin. PMID- 6245703 TI - Inactivation of glycogen synthase alpha by the catalytic subunit of cyclic AMP dependent protein kinase. Kinetics of inactivated forms. PMID- 6245704 TI - Kinetics of reaction of human C1-inhibitor with the human complement system proteases C1r and C1s. PMID- 6245705 TI - Partial purification and characterization of a triacylglycerol-transfer protein from rabbit serum. AB - Rabbit lipoprotein-free serum was found to contain a protein fraction that mediates the transfer of [3H]triacylglycerol from low-density lipoprotein to high density lipoprotein. Fractionation of rabbit lipoprotein-free serum by DEAE Sephadex chromatography, ammonium sulphate precipitation, concanavalin-A Sepharose chromatography, Sephadex G-200 gel filtration, phenyl-Sepharose chromatography and Sephadex G-100 gel filtration, yielded a preparation that had a 500-fold increase in transfer activity compared to that of the starting sample. The transfer activity appeared to reside in a glycoprotein of molecular weight in the range 100 000-155 000 and an isoelectric point at pH 9. PMID- 6245706 TI - In vitro effect of adrenocorticotrophic hormone on the pH profile of tri- and diester lipase activities from rat brain. AB - The influence of adrenocorticotrophic hormone (ACTH) on the hydrolysis of tri- and dioleoylglycerol by a cerebral lipase was studied using a synaptosomal preparation from rat brain as source of enzyme. When ACTH was added to the lipolytic medium, it caused a marked shift of the optimum pH values of catalysis towards alkaline values. In the pH range 5.8-6.5, these shifts resulted in reaction rates 5- to 20-fold higher, depending on the experimental conditions, than those measured without hormone. The ACTH effect was dependent on the NH2 terminal sequence extending through the amino acid residues 15-18. The results suggest that the hormonal influence is specific and mediated through a colipase like effect. PMID- 6245707 TI - Effect of membrane phospholipid composition changes on adenylate cyclase activity in normal and rous-sarcoma-transformed chicken embryo fibroblasts. AB - Adenylate cyclase specific activities in membranes isolated from chicken embryo fibroblasts transformed by Rous sarcoma virus are significantly lower than the specific activity of the enzyme in normal membranes. Since normal and transformed membranes have different phospholipid and fatty acid compositions, adenylate cyclase activities were examined in normal and transformed membranes which had been supplemented with polar head groups or fatty acids. Basal, fluoride, and prostaglandin E1-stimulated activities changed systematically with phospholipid composition. Increases in the primary amino group of the phospholipid polar head groups or the average degree of fatty acid unsaturation both inhibited adenylate cyclase activity. In general, adenylate cyclase activities in normal membranes were more sensitive to phospholipid compositional changes compared to adenylate cyclase in transformed membranes. The data indicate that the lower adenylate cyclase activities in transformed membranes are not solely attributable to phospholipid changes but do suggest that increases in the percentage of phosphatidylethanolamine may contribute to the lower adenylate cyclase activities in transformed membranes. PMID- 6245708 TI - Acetylcholinesterase solubilized from normal and dystrophic muscle by collagenase treatment. AB - The activity of specific acetylcholinesterase, assayed in the presence of an inhibitor of nonspecific cholinesterase, was significantly lower in the leg muscle of dystrophic mice of Bar Habor strain 129 than in that of normal mice. However, the nonspecific butyrylcholinesterase activity was much higher in dystrophic muscle than in normal muscle. Collegenase released more acetylcholinesterase activity into the soluble fraction derived from homogenized normal muscle than into that derived from dystrophic muscle. The collagenase released activity in the normal muscle contained about 95% specific acetylcholinesterase while that from dystrophic muscle contained only 74% specific acetylcholinesterase activity. The acetylcholinesterase activity solubilized by collagenase from control muscle contained the highest activity in 10 S form with decreasing activity of 16 S and 4 S forms, but that from dystrophic muscle contained much less of the 16 S and 10 S forms with more 4 S form, compared to the controls. PMID- 6245709 TI - Involvement of cyclic AMP in carotenogenesis and cell differentiation in Blakeslea trispora. AB - Cyclic adenosine 3',5'-monophosphate (cyclic AMP) was detected in single and mated cultures of Blakeslea trispora. Cyclic AMP levels increased on mating the plus and minus mycelia. Trisporic acid and beta-carotene levels were much higher in synthetic mucor medium supplemented with glycerol as compared to that with glucose. Cyclic AMP induced significant morphological changes in plus and minus strains were comparable to those induced by mating event. PMID- 6245710 TI - The effect of diamide on cyclic AMP levels and cyclic nucleotide phosphodiesterase in human peripheral blood lymphocytes. AB - The effect of diamide (diazene dicarboxylic acid bis[N,N'-dimethylamide) on cyclic AMP levels and cyclic nucleotide phosphodiesterase in human peripheral blood lymphocytes was examined. In the absence of mitogenic lectins, 5 . 10(-3)-1 . 10(-4) M diamide markedly increased intracellular cyclic AMP with variable effects at higher levels. In the presence of phytohemagglutinin or concanavalin A, 5 . 10(-4) M or higher diamide concentrations consistently decreased cyclic AMP levels, usually to control levels or below, while 1 . 10(-4)-1 . 10(-5) M diamide augmented the lectin-induced rise in cyclic AMP. When intact lymphocytes were incubated with diamide, phosphodiesterase activity against both cyclic AMP and cyclic GMP, assayed in homogenates of these cells, was inhibited at concentrations as low as 1 . 10(-6) M. In contrast, when diamide was incubated with phosphodiesterase extracted from lymphocytes there was a dual effect. At low substrate concentrations and high diamide concentrations diamide was a non competitive inhibitor of phosphodiesterase with a Ki of 1.3--2.5 mM for cyclic AMP and 3.3--10 mM for cyclic GMP. In contrast, at high substrate concentrations diamide was an 'uncompetitive' activator of phosphodiesterase activity for both cyclic AMP and cyclic GMP. The effects of diamide could be largely or completely blocked by glutathione or dithiothreitol, indicating that sulfhydryl reactivity was involved in diamide's action on lymphocyte phosphodiesterase activity and intracellular cyclic AMP levels. These data demonstrate that diamide is a phosphodiesterase inhibitor both on phosphodiesterase extracted from lymphocytes and when incubated with intact lymphocytes and that diamide may increase or decrease intracellular cyclic AMP levels depending on the concentration of diamide used. PMID- 6245711 TI - Phosphorylation of a 100 000 dalton component and its relationship to calcium transport in sarcoplasmic reticulum from rabbit skeletal muscle. AB - Sarcomplasmic reticulum from rabbit fast skeletal muscle contains intrinsic protein kinase activity (ATP:protein phosphotransferase, EC 2.7.1.37) and a substrate. The protein kinase activity was Mg2+ dependent and could also phosphorylate exogenous protein substrates. Autophosphorylation of sarcoplasmic reticulum vesicles was not stimulated by cyclic AMP, neither was it inhibited by the heat-stable protein kinase inhibitor protein. The phosphorylated membranes had the characteristics of a protein with a phosphoester bond. An average of 73 pmol Pi/mg protein were incorporated in 10 min at 30 degrees C. Addition of exogenous cyclic AMP-dependent protein kinase increased the endogenous level of phosphorylation by 25-100%. Sarcoplasmic reticulum membrane phosphorylation, mediated by either endogenous cyclic AMP-independent or exogenous cyclic AMP dependent protein kinase, occurred on a 100 000 dalton protein and both enzyme activities resulted in enhanced calcium uptake and Ca2+-dependent ATPase (ATP phosphohydrolase, EC 3.6.1.3), in a manner similar to cardiac microsomal preparations. Regulation of Ca2+ transport in skeletal sarcoplasmic reticulum may be mediated by phosphorylation of a 100 000 dalton component of these membranes. PMID- 6245712 TI - Binding of adenosine diphosphate to human blood platelets and to isolated blood platelet membranes. AB - The equilibrium binding of 14C-labeled ADP to intact washed human blood platelets and to platelet membranes was investigated. With both intact platelets and platelet membranes a similar concentration dependence curve was found. It consisted of a curvilinear part below 20 microM and a rectilinear part above this concentration. At high ADP concentrations, the rectilinear part appeared to be saturable. Because of this, two classes of saturable ADP binding sites were proposed. ADP was partly converted to ATP and AMP with intact platelets while this conversion was virtually absent in isolated platelet membranes. ADP was bound to platelet membranes with the same type of curves found for intact platelets. The ADP binding to the high affinity system, which was stimulated by calcium ions, was nearly independent of temperature and had a pH optimum at 7.8. A number of agents were investigated for inhibiting properties. Of the sulfhydryl reagents only p-chloromercuribenzene sulfonate inhibited both high and low affinity binding systems while iodoacetamide and N-ethylmaleimide were without effect. Compounds acting via cyclic AMP on platelet aggregation, such as adenosine and cyclic AMP itself, had no influence on binding. Some nucleosidediphosphates and nucleotide analogs at a concentration of 100 microM had no, or only a slight, effect on high affinity ADP binding. For some other nucleotides inhibitor constants were determined for both platelet ADP aggregation and ADP binding. The inhibitor constants of ATP, adenyl-5'-yl-(beta,gamma methylene)diphosphate, IDP, adenosine-5'(2-O-thio)diphosphate, for aggregation and high affinity binding were in good correlation with each other. Exceptions formed fluorosulfonylbenzoyl adenosine and AMP. The ATP formation found with intact platelets could be attributed to a nucleosidediphosphate kinase. It was investigated in some detail. The enzyme was magnesium dependent, had a Q10 value of 1.41, a pH optimum at 8.0, was competitively inhibited by AMP and reacted via a ping pong mechanism. All findings described in this paper indicate that platelets as well as platelet membranes bind ADP with the same characteristics and they suggest that the high affinity binding of ADP is involved in platelet aggregation induced by ADP. The results on nucleosidediphosphate kinase did not permit a firm conclusion about the role of the enzyme in induction of platelet aggregation by ADP. PMID- 6245713 TI - Hormonal interactions in mammalian collagenase regulation. Comparative studies in human skin and rat uterus. AB - The production of collagenase by human skin explants in culture is prevented by 10(-8) M dexamethasone, 5 . 10(-4) M dibutyryl cyclic AMP, or 2.5 . 10(-3) M theophylline. Decreases in collagenase activity are paralleled by reductions in the degradation of explant collagen during the culture period. Progesterone, which effectively inhibits collagenase production in rat uterine explant cultures, has no effect on human skin explants. The inhibition by cyclic AMP is nucleotide specific. When partially inhibitory concentrations of dexamethasone and dibutyryl cyclic AMP, or dexamethasone and theophylline, are added to culture medium together, the resultant inhibition is that predicted by additivity. Synergistic inhibition, as observed in rat uterus between progesterone and dibutyryl cyclic AMP, fails to occur. Dexamethasone inhibits the production of collagenase by cultured explants of rat uterus, with complete inhibition occurring at 10(-7) M steroid. Synergism between glucocorticoids and dibutyryl cyclic AMP or between dexamethasone and progesterone could not be demonstrated in the uterine culture system. These results suggest the existence of three regulatory systems for the control of collagenase production in mammalian tissues, and that cooperativity between systems may occur on a tissue-specific basis. PMID- 6245714 TI - Effects of probenecid on transport and metabolism of cyclic AMP by isolated rabbit renal tubules. AB - The effects of probenecid on the transport and metabolism of cyclic [14C]-AMP were studied in isolated rabbit kidney cortex tubules. Incubation in a medium with 10-400 microM probenecid for 30 min caused a 30-70% decrease in the tubular uptake of labeled material from a medium containing 0.1 mM cyclic [14C]AMP. The radioactivity in the tubules, after 30 min incubation, with or without probenecid, was mostly in the form of inosine and hypoxanthine. The disappearance of external cyclic [14C]AMP was retarded by probenecid and the concentration ratio of cyclic AMP to inosine + hypoxanthine was increased. Cyclic AMP phosphodiesterase activities, from both the soluble and particulate fractions of the kidney, were inhibited by probenecid. These findings indicate that the changes caused by probenecid on the renal disposal of extracellular cyclic AMP can be accounted for by a decrease in the accumulation of the products of cyclic AMP metabolism secondary to inhibition of extracellular cyclic AMP phosphodiesterase activity. PMID- 6245715 TI - Characteristics of the guanine nucleotide regulatory component of adenylate cyclase in human erythrocyte membranes. AB - This study probes the structure and mutual interactions of the components of adenylate cyclase. We use a complementation assay which involves the addition of an adenylate cyclase-related guanine nucleotide-binding protein component to a membrane lacking this component to measure guanine nucleotide-stimulated adenylate cyclase. Instead of using detergent extracts we were able to achieve full complementation by mixing intact membrane preparations in the presence of the nucleotide component. Of particular interest was the human erythrocyte membrane which contains very low amounts of catalytic activity and no measurable beta-adrenergic receptor but has normal amounts of the nucleotide component. This component appears to be the same, by several criteria, as components found in pigeon and turkey erythrocytes and in rat liver plasma membrane. The component confers Gpp(NH)p, fluoride, and GTP stimulation of adenylate cyclase along a single reconstitution curve. It is labeled with NAD by cholera toxin, and has an apparent molecular weight of 39 000 upon sodium dodecyl sulfate gel electrophoresis. The presence of the nucleotide unit in the virtual absence of the active catalytic unit allowed us to determine those properties intrinsic to each unit and those conferred by the association of the units. The nucleotide component binds guanine nucleotides weakly in the human erythrocyte membrane, yet produces persistent activation of adenylate cyclase and tight binding (of Gpp(NH)p) upon combination with the catalytic unit. Treatment of the human erythrocyte membrane with N-ethylmaleimide causes a simultaneous diminution in both Gpp(NH)p and fluoride stimulation in reconstituted activities, suggesting that both activities are conferred by the same component. PMID- 6245716 TI - Glutathione reduces cytoplasmic vanadate. Mechanism and physiological implications. AB - The mechanism by which cells reduce cytoplasmic vanadium(V) (vanadate) to vanadium(IV) was investigated using the human red cell as a model system. Vanadate uptake by red cells occurs with a rapid phase involving chemical equilibration across the plasma membrane and a slower phase resulting in a high concentration of bound vanadium(IV). The slow phase was inhibited in glucose starved cells and restored upon addition of glucose indicating an energy requirement for this process. The time course of vanadium(IV) appearance (monitored by EPR spectroscopy of intact cells) paralleled the slow phase of uptake indicating that this phase involves vanadium reduction. The reduction of intracellular vanadate to vanadium(IV) was nearly quantitative after 23 h. The intracellular reduction is not enzymatic, since a similar time course of vanadium reduction and binding to hemoglobin was observed when glutathione was added to a hemoglobin + vanadate solution in vitro. Vanadium(IV) binding to hemoglobin was reduced by addition of ATP, 2,3-diphosphoglycerate or EDTA, probably through chelation of the cation. The stability constant of the ATP-vanadium (IV) complex was determined to be 150 M-1 at pH 4.9. The time course of red cell vanadate uptake and reduction was followed in the concentration range in which approximately 60% inhibition of the (Na+ + K+)-ATPase is observed. It is concluded that vanadate is reduced by cytoplasmic glutathione in this concentration range and that the reduction explains the resistance of the (Na+ + K+)-ATPase to vanadium in intact cells. PMID- 6245717 TI - [Role of free superoxide radicals in the aging of biological objects]. PMID- 6245718 TI - [Nature of paramagnetic centers arising in a gamma-irradiated culture of LL tumor cells]. PMID- 6245719 TI - [Proton magnetic relaxation time of normal and tumor cells]. AB - A proton NMR analysis of an in vitro culture of cells in heavy water has been made. The relaxation times of L-strain cells 929, He-La, transformed and normal embryonic human cells, C3H mice and isolated Yoshida sarcoma tumour cells, as well as of Yoshida sarcoma tumour tissue were determined. It turned out that spin lattice (T1) and spin-spin (T2) relaxation times are characteristic of every cell and fairly different from those of corresponding tissues, which may be used for NMR identification of cells (NMR cytology). Furthermore, it has incontestably been proved that there is an ordered water fraction of cells, which is very slowly exchanged with surrounding heavy water. PMID- 6245720 TI - [Reaction between metal-free porphyrins and sodium in aprotonic solvents]. PMID- 6245721 TI - [Reasons fo the slowing of structural transitions in ferricytochrome c following adsorption]. PMID- 6245722 TI - [Effect of a number of homologous monoatomic alcohols on the activity of Na,K ATPase and its reaction with potassium ions]. PMID- 6245724 TI - [Chemical conversion of iminoxyl spin probes in photoreceptor membranes]. PMID- 6245723 TI - [Ribonuclease hydration and its heat stability in solutions of H2O and D2O]. AB - Ribonuclease hydration in wide concentration and temperature range using differential scanning microcalorimetry and NMR technique was studied. The temperature- concentration equilibrium diagram for H2O--ribonuclease system was suggested. Protein hydration in D2O was shown to be higher than in ordinary water. NMR measurements in dilute protein solutions showed that cooperative temperature denaturation was followed by solvation changes. Models of globular protein hydration are discussed. PMID- 6245725 TI - [Thermoinduced structural changes in the membranes of animal organs following administration of antioxidants and during growth of malignancies]. AB - By means of weak-bound spin probes--stable iminoxyl free radicals differing in the level of hydrophobity there were studied thermoinduced structural transitions in the membranes of cell organells of animal liver after intraperitoneal injection of antioxidants and in the course of malignant growth, and in the nuclear membranes of Ehrlich ascite carcinoma as well. It has been found that during the growth of Ehrlich ascite carcinoma changes in rotationary mobility of probes in cell nuclei isolated from the liver of tumour-carrying animal are similar to the changes observed after antiocidants injection. A different pattern is observed in tumour cells. The membranes of ascite cell nuclei are characterized by a weak dependence of tau c on temperature for both probes. Within the temperature range studied no characteristic structural transitions proceeding in the nuclei of intact animals are observed. PMID- 6245726 TI - [Optical and ESR-spectroscopic study of electronic adducts of oxymyoglobin and oxyhemoglobin]. AB - It has been shown that low temperatures (77 degrees K) irradiation of frozen water-glycerol solutions of oxymyoglobin and oxyhemoglobin induces kinetically stabilized nonequilibrium electronic adducts (MbO2-, HbO2-) at the expense of binding of thermolyzed electrons formed during matrix radiolysis to oxygenated hem iron. The absorption spectra of HbO2-and MbO2- have a wide band with the maximum at 545 nm and Soret's band at 421 nm. At 77 K MbO2- gives the ESR spectrum with g beta 1 = 2.203 and g beta 2 = 2.103. Unlike the latter HbO2- ESR spectrum consists of two signals g beta 1 = 2.234, g beta 2 = 2.135 and g alpha 1 = 2.195, g alpha 2 = 2.103. Two signals in HbO2- spectra are shown to be conditioned by electronic adducts of oxygenated alpha- and beta-subunits. The observed effect points to non-equivalency of O2 in alpha- and beta-subunits of oxyhemoglobin. Binding of inositolhexaphopshate to oxyhemoglobin induces changes in the electron structure of HbO2-active centres. PMID- 6245727 TI - [Theoretical evidence for the need to suppress parasitic recirculation in the futile cycle fructose-6-P--fructose-1,6-P2]. AB - In connection with the discussion of a possible role of the futile cycle fructose 6-P in equilibrium or formed from fructose-1,6,-P2 in the regulation of the carbohydrate energy metabolism, simple stoichiometric models of glycolysis and gluconeogenesis are examined which take account of substrate recirculation in the cycle. The recirculation is shown to involve wasteful expenditure of ATP and to divert fructose-1,6-P2 from glycolytic phosphorylation ADP and fructose-6-P from glucose or glycogen resynthesis. As a result, the glycolytic system loses its capacity to stabilize the level of ATP, while gluconeogenesis proves to be not efficient. From the analysis performed it is concluded that normal energy metabolism should involve allosteric regulatory mechanisms to suppress substrate recirculation in the cycle. PMID- 6245729 TI - [Electron tunneling between photoinduced paramagnetic centers in melanin]. AB - Decay of paramagnetic centres (PC) in irradiated melanin pigment of Cladosporium transchelii K-1 is shown to obey the linear plot of PC concentration vs. logarithm of time. Temperature dependence of decay rate is investigated. The data obtained allow one propose the long-range tunneling of electrons from thermally excited electronic states of anionradical sites in melanin. The photoinduced and thermal processes of electron transfer in melanin are reversible. PMID- 6245728 TI - [Study of the destruction of peroxide radicals in lipids]. PMID- 6245730 TI - [Effect of acetylcholine on the calcium channels of frog atrial trabeculae]. PMID- 6245731 TI - [Effect of the frequency of rhythmic excitation on ouabain binding by giant squid axons]. PMID- 6245732 TI - [Conduction of a nerve impulse along a myelineated fiber while varying the membrane properties of nodes of Ranvier]. AB - The mathematical model of a frog myelinated axon [1, 3] has been used to study the dependence of the conduction velocity (theta) on the parameters of the nodal membrane: its capacity (CN), leakage conductance (gl), sodium and potassium maximum conductances (gNa, gK). Calculations have shown that theta practically does not depend on gK:theta raises only by 3% when gK is diminished to zero. The increase of theta with reducing of gl or CN can be described by formulae: theta (m/s) = 19-300.gl (muS) or theta = 16-1.87.CN(pF) (Fig 1,2). Theta depends strongly on gNa:theta approximately equal to (gNa)7/8 (Fig 3). Due to the capacity of Na channels (determined by the gating charge movement) there is a maximum in the relation between the number of Na channels per node and the theta (Fig 4). A clear-cut maximum does exist also in the curve relating theta to the nodal membrane area (Fig. 5a). The position of the maximum and the shape of this curve depend on gl and CN but not on gNa (Fig. 5b). PMID- 6245733 TI - [Proton magnetic relaxation and thermodynamic parameters of ribonuclease solutions during thermal denaturation]. AB - Heat denaturation of ribonuclease in diluted water solutions was studied by means of proton magnetic relaxation, microcalorimetry and viscosity. It has been shown that heat denaturation of ribonuclease is a one stage process; it involves the whole globule and is accompanied by changes in the state of salvated (water) molecules. A redistribution of water molecules in the hydrate "envelope" of protein changes the character of proton magnetic relaxation of the whole solvent. PMID- 6245734 TI - [Effect of ascorbic acid concentration on the ESR signal intensity of dry tissue]. AB - A high concentration (r greater than 0.9; p less than 0.001) between the intensity of free radical ESR-signal (delta H max = 8-10 oe, g-factor 2.0057) in dry tissues of various organs of quinea pigs and concentration of free ascorbic acid in the same tissues was detected. Additional administration of ascorbic acid did not affect the correlation value of organs. The correlation coefficient was low in blood of control animals (r = 0.27; p greater than 0.05) and increased after administration of ascorbic acid (r = 0.95; p less than 0.001). PMID- 6245735 TI - [Comparative study of the ESR spectra of normal and regenerating liver tissue in mice]. AB - Low temperature ESR spectra of gamma-irradiated samples of mouse liver regenerating after partial hepatectomy were studied. As compared to ESR spectra of gamma-irradiated samples of health animals liver, in regenerating liver samples new ESR signals from paramagnetic centres S(2.0005) and S(2.0025) were revealed; these signals were earlier recorded by the authors in gamma-irradiated samples of hepatoma 22a. It is concluded that the paramagnetic centres S(2.0005) and S(2.0025) are typical of proliferating tissues of different ethiology. PMID- 6245736 TI - [Orientation relationship of the proton resonance lines of water in plant stem capillaries]. PMID- 6245737 TI - DNA sequencing and helix-coil transition. I. Theory of DNA melting. PMID- 6245738 TI - Studies on transfer ribonucleic acids and related compounds. XXVI. Circular dichroic properties of cyclic oligoribonucleotides and their linear counterparts. PMID- 6245739 TI - [Cyclic adenosine-3',5'-monophosphate content in the limbic system structures of the rat brain on the administration of corticosteroids]. AB - The effect of hydrocortisone and DOCA on the cAMP content in the hypothalamus, hippocampus and striate body of the rat brain was investigated. Single (determined after 1 and 24 hours) and repeated (7 days) hydrocortison administration in a dose of 5 mg/100 g body weight was accompanied by an increase in the cAMP concentration in the brain structures under study. Single administration of DOCA in a dose of 0.5 mg/100 g body weight did not produce any changes in the cAMP level in the structures of the rat brain limbic system; however, the dose of 2.5 mg raised the cAMP level. Prolonged administration of the hormone in the above doses dod not change the cAMP level in the brain structures. Only the hippocampus showed a 210% increase in the cAMP level during DOCA administration in a dose of 0.5 mg. PMID- 6245740 TI - [Ultrastructural and functional changes in the synaptosomes of the rat brain on in vitro electrostimulation]. AB - Electrostimulation of suspension of the rat brain synaptosomes causes Ca(2)+ dependent endogenous norepinephrine release and at the same time Ca(2)-dependent increase of the mediator content in the synaptosomes. The activity of cAMP declines under the same conditions. Electrostimulation does not alter the ultrastructure of the synaptosomes but raises the content of high electron density synaptosomes. PMID- 6245741 TI - [Radiation modulation of the activity of the enzymatic systems in isolated plasma membranes in early ontogeny]. AB - The activity of adenylate cyclase (Ac), cAMP phosphodiesterase (PDE) and 5' nucleotidase was studied in plasma membranes from the liver of rat embryo of the 20th day of development normally and after exposure to ionizing radiation. Gamma irradiation of plasma membranes with doses ranging from 0.1 to 100 kR was shown to inhibit the activity of Ac, this effect being more pronounced during stimulation with higher doses of isoproterenol. The activity of 5'-nucleotidase and PDE remained unchanged up to the dose of 100 kR. PMID- 6245742 TI - [Changes in the cytochrone C and A (A3) content in the liver mitochondria of rats with hyperthyroidism]. AB - Thyroxin was administered daily to male Wistar rats aged 1, 3, 12 and 24 months in a dose of 250 g per 100 g body weight. After 9 days there was a significant increase in the content of cytochromes c and a (a(3)). An appreciable rise in the cytochrome c content was recorded as long as after one day, whereas the content of cytochromes a (a(3)) did not exceed normal even after 2 days. Following one day the content of cytochromes a (a(3)) in 3-, 12-, and 24-month-old rats was sightly lower than in normal rats. A significant temporary increase in the c/a (a(3)) ratio was observed after 1-2 days only in 12- and 24-month-old rats. The c/a (a(3)) ratio increased with age. It is suggested that application of thyroid hormones may be promising in studies on the regulation of mitochondrial biogenesis. PMID- 6245743 TI - Urinary dysfunction in the aged: neurological considerations. PMID- 6245744 TI - The neurotoxicity of misonidazole: potential modifying role of phenytoin sodium and dexamethasone. PMID- 6245745 TI - Viruses and winter vomiting disease. PMID- 6245746 TI - Dietary fibre, sodium, and blood pressure. PMID- 6245747 TI - Dietary fibre and blood pressure. PMID- 6245748 TI - Eating and ulcers. PMID- 6245749 TI - Cord blood and breast-milk antibodies in neonatal rotavirus infection. AB - Studies were carried out during an outbreak of rotavirus type 2 infection in a neonatal nursery to determine the protective role of antibodies in cord blood and breast milk. The range, distribution, and geometric mean titres of rotavirus specific antibody in the cord blood were similar among rotavirus-positive and rotavirus-negative neonates, and the amount of virus excreted did not correlate with antibody levels. Despite the protective effect of breast feeding, the pattern of rotavirus-specific IgA and IgG antibodies in the expressed breast milk of mothers of babies who were rotavirus excreters and non-excreters was similar. Nevertheless, a higher proportion of expressed breast milk samples contained rotavirus-specific IgA group 2 (92%) and type 2 (97%) specific antibodies than type I (67%) antibodies, and the geometric mean titres of group 2 and type 2 specific antibodies were tenfold higher than type I antibodies. Among breast-fed babies who excreted rotavirus there was no correlation between type 2 rotavirus specific IgA antibodies in expressed breast milk and the amount of neonatal virus excretion. These studies suggest that factors other than the rotavirus antibodies in expressed breast milk are of importance in preventing rotavirus infection in newborn infants. PMID- 6245750 TI - Herpesvirus hominis type 2 infection in Ibadan. Problem of non-venereal transmission. AB - Examination of sera from blood donors, from patients attending a special treatment clinic, a family planning clinic, and an antenatal clinic showed that the prevalence of herpes virus hominis type 2 antibodies among the adult population in Ibadan is similar to that in other parts of the world. The possibility of non-venereal transmission of herpes virus infection was confirmed by the finding that herpesvirus hominis type 2 could survive on cloth samples under humid tropical conditions for long enough to allow transmission of infection via fomites. PMID- 6245751 TI - Effect of delta 9-tetrahydrocannabinol on hypothalamic thermosensitive units. AB - Thermosensitive anterior hypothalamic neurons (pre-optic region) were studied in urethane and chloralose anesthetized cats in an attempt to characterize the hypothermic action of delta 9-THC at the neuronal level. One hundred and seventy eight single neurons were isolated and subjected to thermal challenge, 66 were found to reproducibly alter firing frequency at a significant level (thermosensitivity (T.S.) greater than 0.75). Twenty-one of these units met the criteria for primary thermodetectors, 34 were heat-sensitive interneurons, and 11 were cold-sensitive interneurons. Administration of delta 9-THC (1.0-2.0 mg/kg i.v.) decreased the spontaneous firing and increased the T.S. of the primary thermodetector units. delta 9-THC also increased the spontaneous firing frequency as well as the T.S. of heat-sensitive interneurons, while decreasing both the T.S. and spontaneous firing of cold-sensitive interneurons. The decreased spontaneous firing of primary thermodetectors could result from altered facilitory or inhibitory influences converging on these cells. The increased thermosensitivity is consistent with the hypothesis that the pre-optic region modulates cannabinoid-induced hypothermia. PMID- 6245752 TI - Effect of antenatal exposure to opiates on the development of opiate receptors in rat brain. AB - The ontogenesis of opiate receptors in several brain regions of the developing rat was measured by specific binding of [3H]methionine-enkephalin ([3H]Met). The amount of [3H]Met bound varied significantly with brain region as well as with age: a transient peak was observed at day 4 post-partum (p.p.) in the cerebellum; a hump was observed at days 8-17 in the brain stem; while in the whole forebrain the adult level was reached at day 17 p.p. Administration of morphine or naloxone to female rats before and during pregnancy significantly altered the regional development of [3H]Met binding sites in the brains of the offspring. These data suggest that the development of [3H]Met binding sites in brain follows a caudal to rostral sequence and that antenatal exposure to opiates affects the development of opiate receptors in brain. The latter effect may be responsible for the neonatal withdrawal symptoms in infants born to addicted mothers. PMID- 6245754 TI - Availability of liposome content to the nervous system. Liposomes and the blood brain barrier. PMID- 6245753 TI - An improved method of preparing rat brain synaptic membranes. Elimination of a contaminating membrane containing 2',3'-cyclic nucleotide 3'-phosphohydrolase activity. AB - Synaptosomes were prepared from rat cortex by subjecting a washed crude mitochondrial pellet to centrifugation first on discontinuous Ficoll-isotonic sucrose gradients and then on discontinuous sucrose gradients. The synaptosome fraction, collected from the 7.5-14% Ficoll band (II), was further separated into two additional fractions, designated IIA and IIB, which bank at the 0.32-1.05 M and at the 1.05-1.6 M sucrose interfaces, respectively. Electron microscopic analysis showed that fraction IIB contained synaptosomes and extra terminal mitochondria and was essentially free of membrane fragments. Further characterization showed that IIB contained 69% of the protein and 83% of the lactic dehydrogenase activity of fraction II and had a specific activity of a 2',3'-cyclic nucleotide 3'-phosphohydrolase approximately 1% of that obtained with myelin. Fraction IIA had approximately 50% the specific activity of the 2',3'-cyclic nucleotide 3'-phosphohydrolase found in myelin. Synaptic plasma membranes were prepared by lysing fraction IIB in 1 mM sodium phosphate, 0.1 mM EDTA at pH 8.5 and subjecting this preparation to centrifugation on a discontinuous sucrose density gradient. Enzymatic analysis indicated that membranes banding at the 0.6-0.8 M sucrose interface had high specific activities of plasma membrane enzymes (e.g. acetylcholinesterase, ATPase, 5'-nucleotidase). The specific activity of the (Na+ + K+)-ATPase in the purified membrane preparation was 8-fold higher than that in the original homogenate. Specific activities of various marker enzymes indicated that the composition of these membrane preparations for the most part was synaptic plasma membranes, approximately 7% mitochondrial outer membranes and 3% a membrane containing 2',3' cyclic nucleotide 3'-phosphohydrolase activity. The polypeptide compositions of three possible contaminating membranes and of synaptic membranes were compared by electrophoresis in 6-20% gradient polyacrylamide gels in the presence of sodium dodecyl sulfate. Whereas mitochondrial and myelin membranes had distinct compositions, the compositions of the microsomal and synaptosomal plasma membranes were similar. Synaptic plasma membranes contained at least 27 polypeptides; the three major polypeptides had molecular weights of 103,000; 54,000; and 50,000. The major polypeptides of soluble synaptosomal proteins had molecular weights of 54,000 and 42,000. PMID- 6245755 TI - Brain nucleotides in naive and handling-habituated rats: differences in levels and drug-sensitivity. PMID- 6245756 TI - Ontogeny of beta 1- and beta 2-adrenergic receptors in rat cerebellum and cerebral cortex. AB - The development of beta 1- and beta 2-adrenergic receptors was studied in rat cerebral cortex and cerebellum. In the cerebral cortex, which contains mostly beta 1-adrenergic receptors, total beta-adrenergic receptor density increased sharply between postnatal days 10 and 21. The density of receptors remained fairly constant through 6 weeks of age and then subsequently declined. The proportion of beta 1 and beta 2 receptors was relatively constant throughout the development of the cerebral cortex. The development of the two receptor subtypes thus paralleled the development of total beta-adrenergic receptors in the cerebral cortex. The ontogeny of beta-adrenergic receptors in the cerebellum, which contains mainly beta 2 receptors, was strikingly different from that observed in the cortex. Total cerebellar beta receptor density exhibited a slow but steady increase from postnatal day 5 through day 42. The density of receptors then plateaued and remained constant until the animals were approximately 6 months of age. Unlike the results obtained in the cortex, the relative proportions of beta 1 and beta 2 receptors in the cerebellum changed markedly during development. Between postnatal days 8 and 13 approximately 18% of the receptors were of the beta 1 subtype. This proportion steadily decreased with age, and in 3- and 6-month-old animals only approximately 2% of the receptors were of the beta 1 subtype. The results demonstrate that the two subtypes of beta adrenergic receptors can have different developmental patterns in the same brain area, and that a single receptor subtype can follow different developmental patterns in different brain regions. Possible correlations between the ontogeny of beta 1 and beta 2 receptors and various developmental events are discussed. PMID- 6245757 TI - Corticotrophin and corticosterone secretory patterns following acute neurogenic stress, in intact and in variously hypothalamic deafferented male rats. AB - Adult male rats, intact (N) or bearing complete (CHD), anterior (AHD), or posterior (PHD) hypothalamic deafferentations, were acutely exposed to either visual or audiogenic stimulation. At 2, 4, 10 or 30 min following the onset of stress exposure the animals were decapitated and trunk blood was collected for ACTH (RIA) and corticosterone (CS, CBG) determinations. Basal serum concentrations of both hormones were elevated in CHD and AHD, but not in PHD animals as compared to N animals. In N rats, exposure to both stresses resulted in elevated serum ACTH and CS concentrations, with the ACTH response to audiogenic but not visual stimulation being biphasic. In CHD animals, serum ACTH concentrations decreased, and those of CS were unchanged following stress exposure. While audiogenic stimulation caused elevation in serum levels of both hormones in AHD rats, the normal ACTH and CS response to visual stimulation were completely abolished by anterior hypothalamic deafferentation. In PHD animals, no ACTH response to either of the stress exposures was apparent; in spite of this, partial CS responses were elicited. These data thus describe the temporal aspects of the ACTH and CS secretory responses to different neurogenic stresses, and provide insight into the neural pathways mediating these responses. PMID- 6245758 TI - Dissociation of supraspinal and spinal actions of morphine: a quantitative evaluation. AB - Opiate suppression of spinal withdrawal reflexes was tested in rats with lesions of several spinal funiculi to determine the relative contribution of supraspinal descending systems. The latency of tail-flick to noxious heat was used to assess "analgesia". The effect of lesions of dorsolateral funiculus (DLF), dorsal columns (DC) and ventral quadrant (VQ) were compared to that of sham operations. None of the lesions produced a change in baseline latency. Each animal was tested with varying doses of morphine sulfate over several weeks. Only DLF lesions consistently antagonized tail-flick suppression by morphine across the dose range studied (5-15 mg/kg i.p.), although VQ lesions were somewhat effective. The reduction of morphine's action was proportionally greater for lower doses. The results indicate that both spinal and supraspinal sites contribute significantly to the analgesia produced by systemic administration of opiates. PMID- 6245759 TI - Electrical activity recorded from thin sections of the bed nucleus of the stria terminalis, and the effects of neurotensin. AB - Effects of neurotensin on neurons in the bed nucleus of the stria terminalis (BST) were studied in vitro in thin brain sections of the guinea pig. Electrical stimulation to the stria terminalis (ST) elicited a negative field potential in the BST. The field potential was markedly suppressed in the medium containing Ca2+ at a low concentration of Mg2+ at a high concentration. BST neurons discharged in response to ST stimulation. Some of them also fired spontaneously. Neurotensin excited about two-thirds of BST neurons at concentrations of 0.35-35 nM. This excitation was not blocked when synaptic transmission was blocked in a medium containing Ca2+ in a low concentration and Mg2+ in a high concentration. These observations suggest that neurotensin is an excitatory transmitter or modulator in the amygdalo-BST projection. PMID- 6245760 TI - Effects of combined administration of amphetamine and iprindole on brain adrenergic receptors. PMID- 6245761 TI - Electrophysiological identification of mesencephalic ventromedial tegmental (VMT) neurons projecting to the frontal cortex, septum and nucleus accumbens. AB - The electrophysiological properties of neurons located in the mesencephalic ventromedial tegmentum (VMT) and the organization of the efferents of these neurons to the frontal cortex, the septum, the nucleus accumbens and the head of the striatum were studied in ketamine-anesthetized rats. The projections of the VMT cells were determined through use of the antidromic activation method. Our results show that VMT projections to different target areas originate mainly from different VMT neurons. However, in some cases single VMT neurons were found to send axon collaterals to two different areas. Three branching patterns were observed: septum-cortex, septum--nucleus accumbens and septum--striatum. The occasional observation of temporally distinct antodromic responses from a single area was considered to result from activation of different branches of the arborizing axon. The distribution of antidromic response latencies for VMT projections to each structure is discussed in relation to the question of dopaminergic versus non-dopaminergic mesolimbic and mesocortical systems. PMID- 6245762 TI - Spinal noradrenergic terminal system mediates antinociception. AB - Intrathecal administration of norepinephrine (NE) into the lumbar subarachnoid space of rats and cats implanted with chronic spinal catheters produced a strong, dose-dependent, behaviorally defined analgesia. The effect appeared mediated by an alpha-receptor inasmuch as phenylephrine, but not isoproterenol produced the intrathecal effect. Moreover, the antinociceptive effect of NE was antagonized by the prior systemic or intrathecal administration of phentolamine (an alpha blocker), but was unaffected by pretreatment with propranolol (a beta-blocker). The effect of intrathecal NE was significantly potentiated by prior administration of Lilly 51641 (a monoamine oxidase inhibitor) and protriptyline (a re-uptake inhibitor), and was not antagonized by the intrathecal administration of a non-specific vasodilator, papaverine. The antinociceptive effect of intrathecal NE showed tachyphylaxis following repeated injections. No cross-tolerance between intrathecal NE and morphine was observed, suggesting that the spinal action of morphine is not mediated by spinal noradrenergic terminals. Importantly, naloxone had no effect on the intrathecal NE effect. The present data provide further evidence for the modulatory role of a spinal noradrenergic system on the spinal processing of nociceptive transmission. PMID- 6245763 TI - Inquiry into endorphinergic feedback mechanisms during the development of opiate tolerance/dependence. AB - Met-enkephalin and beta-endorphin levels were determined in the pituitary and brain of rats after treatment for several weeks with either agonists of high receptor affinity, such as levorphanol and etorphine, or with the narcotic antagnoist naloxone. Long-term activation of opiate receptors failed to change the endorphin levels in restricted areas of brain and pituitary, although a high degree of tolerance/dependence is apparent in those animals. Chronic blockade of opiate receptors by naloxone also fails to affect endorphin levels in the pituitary, but selectively increases metenkephalin levels in the striatum. The present data do not support the notion of negative feedback mechanisms to regulate endorphingergic functions during the development of opiate tolerance/dependence. PMID- 6245764 TI - Feedback control of noradrenaline release as a function of noradrenaline concentration in the synaptic cleft in cortical slices of the rat. AB - Cortical slices incubated with [3H]noradrenaline (NA) were used to study quantitatively the infelucne of the NA concentration in the synaptic cleft on electrically induced release of [3H]NA from adrenergic nerve terminals. Stimulation-induced [3H]-overflow was regarded to be proportional to the NA concentration in the synaptic cleft. High concentrations of piperoxan or clonidine were used to block, or maximally stimulate, respectively, the presynaptic alpha-receptors and thus to eliminate feedback control. These two extreme conditions were thought to delineate maximal feedback range. With alpha receptors not artifically manipulated, [3H]overflow increased with stimulus intensity, yet not in proportion to the [3H]-overflow when the presynaptic alpha receptors were blocked, demonstrating increasing feedback inhibition with increasing NA concentrations in the synaptic cleft. Feedback inhibition of NA release was shown to depend in an exponential fashion on NA concentration in the synaptic cleft. The slope of the regression line indicated that maximal inhibition of NA release occurred with NA concentrations in the synaptic cleft 65,000--700,000 times higher than threshold concentration. Data from experiments with different stimulus rates also supported the notion of feedback control of NA release. PMID- 6245765 TI - Control of opiate receptor-adenylate cyclase interactions by calcium ions and guanosine-5'-triphosphate. AB - Adenylate cyclase of homogenates of NG108-15 neuroblastoma x glioma hybrid cells is activated by low concentrations of Ca2+ ions and is inhibited by higher (greater than 0.1 mM) concentrations of Ca2+ ions. Activation of either opiate receptors by 10 microM morphine or alpha-adrenergic receptors by 10 microM norepinephrine inhibits adenylate cyclase by 55% in the absence of Ca2+ ions, and inhibits the Ca2+-dependent activation of adenylate cyclase by more than 90%. Concentrations of Ca2+ ions greater than 0.1 mM inhibit adenylate cyclase and also reduce the extent inhibition of adenylate cyclase by morphine but not by norepinephrine. Guanosine-5'-triphosphate (0.1-1 microM) is required for inhibition of adenylate cyclase by morphine. The results show that morphine inhibits adenylate cyclase by a guanosine-5-triphosphate-dependent process and that the extent of inhibition of adenylate cyclase by morphine or norepinephrine is a function of the Ca2+ ion concentration and the proportion of adenylate cyclase molecules that are activated or inhibited by Ca2+ ions. PMID- 6245766 TI - Microinjection of morphine within nucleus raphe magnus and dorsal horn neurone activities related to nociception in the rat. AB - The hypothesis of an increase by morphine of descending inhibitory controls acting upon the transmission of painful messages at the spinal level has been directly investigated in intact anaesthetized rats. The analgesic efficacy of morphine microinjections (5 micrograms in 0.2 microliter saline) applied within the nucleus raphe magnus (NRM) was examined using the threshold for vocalization after electric shock to the tail as a test: a mean threshold increase of 57% was observed. A few days later, the effects of similar microinjections upon dorsal horn cell activities were studied in acute experiments in the same animals. The response of dorsal horn convergent units induced by the activation of large myelinated (Aa) afferent fibres were unaffected by the microinjection of morphine within the NRM. In the case of the responses of convergent units induced by the activation of unmyelinated (C) afferent fibres, two different results were obtained after microinjection of morphine within the NRM: 8/14 units were not affected and 6/14 were clearly excited. A transient reversal of the excitatory effects was observed after the systemic administration of the opiate antagonist naloxone. The responses of marginal layer cells (lamina 1) were unaffected by the microinjection of morphine within the NRM. These unexpected results are discussed in view of the fact that they conflict with current concepts regarding morphine analgesia. PMID- 6245767 TI - Potentiation of transmission from C-fibers to dorsal horn neurons after tetanus of peripheral nerve. PMID- 6245768 TI - Glutamate- and veratridine-elicited accumulations of cyclic AMP in brain slices: a role for factors which potentiate adenosine-responsive systems. PMID- 6245769 TI - Analgesia and hyperalgesia produced in the rat by intrathecal naloxone. PMID- 6245770 TI - Intracerebral naloxone and the reaction to thermal noxious stimulation in the rat. PMID- 6245771 TI - Some responses of the immature fowl to the withdrawal of a stressor. AB - 1. Light Sussex chicks were treated with corticotrophin (30 IU/kg) five times a week from hatching to 3 weeks of age. Their responses to the cessation of treatment were determined over the subsequent 2 weeks. 2. Growth rate was impaired by the treatment but had returned to normal after 7 d. 3. Adrenal mass was not affected by treatment but hypertrophy was evident after 14 d of recovery. Relative adrenal weight was greater in the treated group throughout the recovery period. 4. Adrenal cholesterol stores were depleted at the end of treatment, were repleted after 7 d but significantly depleted again at 14 d. 5. Plasma glucose concentration was not affected by treatment but birds were hyperglycaemic 7 and 14 d after treatment had ceased. 6. Plasma free fatty acid (FFA) concentrations were not affected at any time. 7. Plasma corticosterone concentration was not affected by the treatment but 7 d later it was greater in the treated birds. 8. Significant correlations between plasma glucose, FFA and corticosterone were found. PMID- 6245772 TI - Membrane electricity as a convertible energy currency for the cell. AB - The role of transmembrane electric potential difference (delta psi) in mitochondria, chloroplasts, and bacteria has been considered. Since the electric capacitance of membranes is much lower than the pH buffer capacitance of water phases, delta psi proves to be the primary form of energy produced by generators of electrochemical H+ potential difference (delta mu-H). There are 11 distinct types of delta mu-H-generating systems in coupling membranes, involved in respiratory and light-dependent electron and proton transfer, as well as in ATP and PP1 hydrolysis and synthesis. Bacteriorhodopsin is the simplest delta mu-H generator. However, even in this case, the molecular mechanism of delta psi production remains obscure. Many types of work can be supported by delta mu-H with no ATP involved so that delta mu-H proves to be not only a transient intermediate of oxidative and photosynthetic phosphorylation but also a convertible energy currency for the cell. Among the delta mu-H-supported activities, mechanical work was recently demonstrated. It can be exemplified by the motility systems of (i) flagellar bacteria and (ii) blud--green algae. As was found in multicellular cyanobacteria, delta mu-H can be used for a power transmission over distances as long as 1 mm. It seems to be probable that in large cells of eukaryotes (e.g., in muscle fibers) giant mitochondria may serve as power-transmitting structures. Na+--K+ gradients can be used to stabilize delta mu-H in bacteria. It is suggested that the primary function of unequal distribution of these cations between the microbial cell and the medium is delta mu-H buffering. PMID- 6245773 TI - The variability, arrangement, and rearrangement of immunoglobulin genes. AB - The multiplicity of heavy-chain variable-region (VH) genes in mouse and human DNA has been estimated using a mouse heavy-(H) chain cDNA clone. We found about 10 hybridization components in mouse DNA and about 20 components in human DNA. Cross hybridization studies of variable region (V) genes indicate that these components represent the numbers of genes within the VH subgroups of each of these species. The arrangement and rearrangement of the H-chain gamma subclasses have been studied in order to assess possible mechanisms of the H-chain switch. Evidence has been found for rearrangement events involving the gamma 2a and gamma 2b constant-region (CH) genes in DNA from cells making IgG2a and IgG2b respectively. In addition we found that cells making IgG2a lack detectable genes for gamma1 and gamma 2b. Both sets of observations are discussed in relation to H-chain diversity and the switch. PMID- 6245774 TI - Cyclic AMP metabolism and lipolysis in cultured human adipocyte precursors. AB - Triacylglycerol breakdown (lipolysis) results from a series of reactions culminated by activation of "hormone-stimulated" triacylglycerol lipase, an enzyme unique to adipose tissue. We have studied various components of the lipolytic process in human omental adipocyte precursors differentiating in culture. The levels of cyclic AMP, the "second messenger" of lipolytic hormones, were about sixfold higher in fat cell precursors than those in abdominal skin fibroblasts. L-Isoproterenol resulted in significant elevation of cyclic AMP levels in both cell types. Preincubation of intact adipocyte precursors with insulin resulted in significant enhancement of "low Km" cyclic AMP phosphodiesterase activity; in contrast, this hormone had no effect on fibroblast phosphodiesterase activity, a distinctive biochemical difference despite the morphological similarities between the two cell types during the early stages of adipocyte precursor maturation. Incubation of adipocyte precursors with isoproterenol resulted in the release of fatty acids into the medium, findings indicative of "hormone-stimulated" lipase activity and, hence, the operation of the entire "lipolytic cascade"; isoproterenol-stimulated lipolysis was inhibited by insulin. Release of fatty acids from fibroblasts was not observed. Thus, "hormone-stimulated" lipolysis and insulin stimulation of cyclic AMP phosphodiesterase activity are expressed during early stages of human adipocyte precursor differentiation. PMID- 6245775 TI - Cross-linking of cytochrome oxidase subunits with difluorodinitrobenzene. AB - Cytochrome c oxidase was treated with 1,5-difluoro-2,4-dinitrobenzene at molar ratios (DFDNB:oxidase) varying from 5 to 625. At the lowest ratio, there was virtually no effect of the probe on oxidase activity or on migration of oxidase subunits on sodium dodecyl sulfate--polyacrylamide disc gel electrophoresis. At ratios of 25 and greater, there was loss of oxidase activity and a change of the pattern of subunit migration on sodium dodecyl sulfate electrophoresis. (i) Activity loss was probably a result of severely perturbing the cytochrome c binding site since oxidase activity with a low molecular weight reductant (N,N,N',N'-tetramethylphenylenediamine) was unaltered. Also unaltered were the oxidized, reduced, and carbon monoxide binding spectra of the treated oxidase. (ii) The staining pattern on sodium dodecyl sulfate electrophoresis showed that subunits III and VI disappeared from their normal positions on the gel. A new band of higher molecular weight accompanied their loss from the gel indicating that the two subunits were being cross-linked. Subunits III and VI are thus shown to have two reactive groups within 4.8 A (1 A = 0.1 nm) of one another. This proximity has not been detected with other probes that react with the same groups. PMID- 6245776 TI - Poly(A) polymerase activity in ethionine-intoxicated rats: the relative effectiveness of disaggregated and intact polyribosomes as primers for poly(A) polymerase. AB - Ethionine intoxication causes a change in the metabolism of poly(A) sequences on the 3' OH terminus of mRNA in rat liver in vivo. In an attempt to determine the factors responsible for these changes, nuclear and cytoplasmic poly(A) polymerase activities and the state of the primer were examined in vitro. Requirements for optimal enzyme activities were determined. The nuclear and cytoplasmic enzymes had different K+, Mn2+, and poly(A) primer optima. The levels of nuclear and cytoplasmic poly(A) polymerase activity were shown to decrease following ethionine intoxication. Poly(A)+ RNA isolated from the livers of saline- and ethionine-treated rats served equally well as primers for the cytoplasmic poly(A) polymerase. Disaggregated polysomes were seven times more effective as primers than were intact polysomes. The results suggest that the mRNP particle which is released from polysomes as a result of ethionine intoxication functions better as a poly(A) polymerase primer than does the intact polysome. PMID- 6245777 TI - Properties of a phosphoprotein phosphatase from rat epididymal fat pads: deactivation of hormone-sensitive triglyceride lipase and activation of glycogen synthase in adipose tissue. AB - A phosphoprotein phosphatase has been partially purified from rat epididymal fat pads by a procedure utilizing ammonium sulfate and ethanol precipitations and chromatography on DEAE-Sephadex A-50. The phosphatase was eluted from Sephadex G 75 columns with an apparent molecular weight of 28 000. The phosphoprotein phosphatase catalyzed the reversible deactivation of protein kinase activated chicken adipose tissue hormone-sensitive triglyceride lipase. Phosphatase activity measured with activated triglyceride lipase as substrate was completely dependent upon the presence of metal ions (Mg2+, Ca2+, or Mn2+) and was inhibited by inorganic phosphate and adenine nucleotides. The fat pad phosphatase increased the rate of activation of glycogen synthase in rat adipose tissue infranatant fractions from fed and 24-h fasted rats but had little or no effect on synthase activity in infranatant fractions from rats fasted for 48 h. Fasting had no effect on rat fat pad phosphatase activity measured with triglyceride lipase as substrate, but phosphatase activity was decreased in preparations from diabetic rats. PMID- 6245778 TI - Pancreatic islet tumour of childhood. PMID- 6245779 TI - Occupational lung cancer and smoking. PMID- 6245780 TI - Postirradiation mixed mullerian tumors of the uterus: a comparative clinicopathologic study. AB - Nine patients with mixed mullerian tumors (MMT) of the uterus associated with a history of prior pelvic irradiation were compared clinically and pathologically with 8 nonirradiation-associated MMT control patients. Patients with postirradiation tumors presented at a younger age and with symptoms indicative of extensive intraabdominal disease while the nonirradiation-associated control patients were initially evaluated for abnormal uterine bleeding only. Two-thirds of the postirradiation patient's neoplasms were classified as heterologous MMT (mixed mesodermal tumor) whereas 62% of the control patient's neoplasms were homologous MMT (carcinosarcoma). Regardless of clinical presentation or histologic composition both groups fared equally poorly with average survival times of six and seven months, respectively. We were unable to substantiate that some histologic components of uterine MMT denote a poorer prognosis than others or that the postirradiation MMT behaves any differently, in the course of time, from the sporadic type. When uterine MTT is encountered in a patient under 55 years of age, the possibility that pelvic irradiation was administered some years before should be raised. PMID- 6245781 TI - Lymph node invasion and prognosis in nephroblastoma. AB - Five hundred and twelve children with Wilms' tumor Stages I, II, and III registered to the International Society of Pediatric Oncology (SIOP) nephroblastoma trial were analyzed as to the prognostic value of metastatic lymph node involvement. The lymph nodes of 300 patients were submitted for microscopic examination; malignant invasion was reported in 15%. The disease-free and the actuarial survival rates for patients with metastatic lymph node invasion were significantly worse than for those without metastatic lymph node involvement. Radical lymph node dissection neither improved the cure rate nor decreased the rate of abdominal recurrence in patients with lymph node metastases. PMID- 6245782 TI - Evaluation of response to chemotherapy with fiberoptic bronchoscopy in non-small cell lung cancer. AB - Fiberoptic bronchoscopy was performed before and during administration of chemotherapy in 32 patients with unresectable non-small cell carconoma of the lung. Pretreatment findings varied with the histologic cell type. Direct visual and/or pathologic evidence of cancer was obtained in 11 of 11 patients with epidermoid, in 5 of 7 with large cell, and in 9 of 14 with adenocarcinoma. In 5 of the 32 patients, intrathoracic tumor was documented at bronchoscopy but not by chest x-ray. During chemotherapy, one of five episodes of response and eight of 21 episodes of chest tumor progression were detected solely by bronchoscopy, while in an additional two objective responses and six progressions, bronchoscopic and radiographic findings simultaneously improved or deteriorated. The likelihood of documenting disease progression by bronchoscopy also depended upon the histologic type of cancer. Enlarging chest tumor found solely by chest x ray occurred exclusively in patients with large cell carcinoma and adenocarcinoma. During chemotherapeutic treatment of our pateints, addition of serial bronchoscopic examinations to standard means of assessing tumor response frequently allowed the earlier discontinuation of an ineffective drug regimen. PMID- 6245783 TI - Wilms' tumor in the adult patient: diagnosis, management, and review of the world medical literature. AB - Adult Wilms' tumor, unlike that of childhood, is a rare disease. A total of 167 cases have been reported in the world medical literature. However, there is controversy as to whether all of these are indeed truly nephroblastomas or in actuality represent sarcomatoid renal carcinomas. The pathologic hallmarks of this neoplasms are distinctive and it is histologically similar to the childhood tumor. The therapeutic guidelines and surgical principles that govern childhood Wilms' tumor should be applied to adult Wilms' tumor. Agressive and multimodal therapy should be the hallmark of management of this rare neoplasm. Three well documented cases of Wilms' tumor in the adult patient are presented. Of these three patients, two who presented with Stage IV disease and were treated with multimodal therapy were rendered free of disease, one living at 24 months and the other dead at five months. PMID- 6245784 TI - Retroperitoneal malignant fibrous histiocytoma. AB - The case report of a patient with a large retroperitoneal malignant fibrous histiocytoma treated with a combination of radiation therapy and surgery is presented. At the time of the first laparotomy, the lesion was deemed unresectable and biopsied. Reexploration after irradiation to a dose of 3800 rad showed the tumor to be more than 50% smaller and easily resectable. There has been no recurrence during the ensuing two and a half years. PMID- 6245785 TI - Wilm's tumor: an update. PMID- 6245786 TI - Childhood urologic cancer therapy related sequelae and their impact on management. PMID- 6245787 TI - Estrogen receptor concentrations in 269 cases of histologically classified human breast cancer. AB - This report provides a histological review of 264 female primary breast cancers analyzed for estrogen receptor protein (ER). We also describe 5 cases of male breast cancer all of which bound estradiol specifically. Generally the ER concentrations were lower in the tumors of premenopausal women than in those of postmenopausal women. Three types of cancer with specific morphological features were shown to have ER concentrations that differed significantly from the other types of cancer. Medullary and comedo carcinoma had very low and papillary carcinoma very high levels of ER. No obvious trend in ER concentration was found in unspecified ductal carcinoma, colloid carcinoma, nor in lobular carcinoma. A positive correlation was demonstrated between ER content and degree of differentiation in ductal carcinoma. Cancer with lymphoid infiltration generally showed low ER levels. PMID- 6245788 TI - Synovial sarcoma: an electron microscopic study of monophasic and biphasic forms. AB - Seven cases of synovial sarcoma were studied by electron microscopy. The 4 cases of the monophasic spindle type contained elongated cells arranged in sheets and cords; ultrastructurally the cells contained many cytoplasmic processes and were scattered in an amorphous matrix. The monophasic spindle type demonstrates ultrastructural characteristics that are unique and serve to differentiate it from the biphasic pattern and from fibrosarcoma. Three cases of the biphasic variety demonstrated cytologic characteristics of a true glandular epithelium and a malignant spindle cell stroma. The epithelial nature of the biphasic variety is a feature that raises doubt whether synovium is the stem cell. PMID- 6245789 TI - Expression of A and B tissue isoantigens in benign and malignant lesions of the breast. AB - AB isoantigens are widely distributed in human tissues and loss of AB isoantigen expression has been shown to be an early marker for carcinomatous transformation in some tissues. We therefore applied the Specific Red Cell Adherence Reaction (SRCA) for detection and localization of AB isoantigens in tissue to the study of benign and malignant proliferative lesions of the breast. Twenty-nine lesions in 19 patients were studied. AB isoantigen expression in normal breast tissue was found to be largely confined to the mammary duct system. Loss of AB isoantigen expression was a consistent feature of intraductal carcinoma (3 of 3 cases). Proliferative lesions associated with fibrocystic disease also demonstrated varying degrees of isoantigen loss (simple cystic disease, 3 of 8 cases; intraductal hyperplasia, 6 of 7 cases; sclerosing adenosis, 4 of 4 cases; and intraductal papillomatosis, 7 of 7 cases negative for isoantigen). In contrast to other systems, loss of AB isoantigen expression in the breast appears to be a consistent marker of apparently benign proliferative duct lesions associated with fibrocystic disease, as well as duct carcinoma. The early loss of AB isoantigen expression in these histologically benign lesions supports a possible link between fibrocystic disease and mammary carcinoma. In contrast to other tissues, loss of AB isoantigen expression in proliferative breast lesions is not necessarily evidence of malignancy. PMID- 6245790 TI - An in vitro model of pancreas carcinoma: N-nitroso-bis(2-hydroxypropyl)amine effects. AB - The carcinogenic effects of BHP in organ-cultured embryonic rat pancreas was demonstrated by both the transplacental route followed by organ culture and by direct addition on BHP to the culture medium. Both methods appeared efficient for in vitro induction of adenocarcinoma. The incidence of carcinoma was 70% by direct addition and 55% through transplacental administration. No acinar cell carcinoma developed in vitro, but the incidence of islet adenoma (54%) and islet carcinoma (11%) were relatively high. Transplacentally, BHP failed to produce any pancreatic tumor in vivo. PMID- 6245791 TI - Differences in metabolism and cytotoxicity between 9-beta-D arabinofuranosyladenine and 9-beta-D-arabinofuranosyl-2-fluoroadenine in human leukemic lymphoblasts. PMID- 6245792 TI - Serum ferritin as a guide to therapy in neuroblastoma. AB - Elevated serum ferritin levels without a corresponding increase in tissue iron storage have been observed in patients with certain cancers. Increased synthesis of ferritin by cancer cells has also been reported. In order to see whether similar phenomena occurred in patients with neuroblastoma, we have screened serum ferritin levels in 58 children with neuroblastoma by counterelectrophoresis using antibody to human ferritin. Increased ferritin levels in serum, positive by counterelectrophoresis (greater than or equal to 400 ng/ml), correlated well with the presence of active disease (p less than 0.001 by Fisher's exact 2 X 2 test). A longitudinal study of serum ferritin levels in 34 of the 58 patients showed the same association of elevated serum ferritin with active disease; a return of ferritin levels to the normal ranges coincided with remission. Primary neuroblastoma tumors and cells from neuroblastoma cell lines contained ferritins with the electrophoretic characteristics different from normal liver ferritin. Supernatant fluids from six neuroblastoma cell lines grown in culture also contained ferritin. These findings suggest that the increased ferritin in the serum of patients is derived from the tumor. The serum ferritin level could be used as indicator of disease activity and as a guide to therapy. PMID- 6245793 TI - Mechanisms of sensitivity and resistance of murine tumors to 5-fluorouracil. AB - The biochemical basis for the resistance of murine leukemia P388 to 5 fluorouracil (FUra) was systematically investigated by examining the transport and metabolism of FUra, or its anabolites, as well as the inhibition of enzymes and processes known to be affected by the drug. Of these parameters, only three were found to be altered significantly in the resistant line: (a) the enzyme required for the phosphorylation of uridine 5'-monophosphate to uridine 5' diphosphate was present at a significantly lower specific activity in the resistant line than in its sensitive counterpart; (b) the rates of generation and persistance of 5-fluoro-2'-deoxyuridine 5'-monophosphate were significantly lower and shorter in the variant; and (c) there was a 1.6- and 3-fold decrease in the incorporation of FUra into polyadenylic acid-containing RNA and polyadenylic acid lacking RNA, respectively, in resistant versus sensitive cells. Taken together, these findings suggest a dual mechanism for resistance to FUra in these leukemic cells, namely, a depressed capacity to generate di- and triphosphates of the riboside and deoxyriboside of the drug leading to lower pools of the proximate antimetabolite, fluorouridine 5'-triphosphate, and accelerated excretion of 5 fluoro-2'-deoxyuridine 5'-monophosphate, so that thymidylate synthetase is perturbed in a less than lethal way. PMID- 6245794 TI - Characteristics of mitochondria isolated by rate zonal centrifugation from normal liver and Novikoff hepatomas. AB - Mitochondria were isolated from whole homogenates of normal liver and Novikoff hepatomas using reorienting rate zonal centrifugation on sucrose gradients. The activities of several mitochondrial-specific enzymes and ultrastructure were compared in the two tissues. Our results indicate that cytochrome oxidase, lipoamide dehydrogenase, malate dehydrogenase, and succinate dehydrogenase activities are all higher in liver homogenates than in Novikoff hepatoma homogenates. Mitochondrial hexokinase, however, is much greater in the hepatoma than in liver. The activity of these enzymes in isolated mitochondria displayed a much different pattern. Both cytochrome oxidase and succinate dehydrogenase activities were higher in hepatoma mitochondria than in liver mitochondria. Lipoamide dehydrogenase and malate dehydrogenase, conversely, were higher in liver mitochondria. Hexokinase was found to be virtually absent in liver mitochondria but plentiful in hepatoma mitochondria. Ultrastructural studies have shown that the hepatoma mitochondria are much smaller in size, which results in a decreased rate of migration into the gradient. These studies have also shown that normal liver consists of predominantly "condensed" forms of mitochondria, whereas hepatoma contained a majority of "twisted" species. Experiments using 1% bovine serum albumin in the homogenization procedures and in the gradient have confirmed earlier observations that bovine serum albumin is essential for optimal isolation of neoplastic mitochondria. PMID- 6245795 TI - Active versus passive absorption kinetics as the basis for selective protection of normal tissues by S-2-(3-aminopropylamino)-ethylphosphorothioic acid. AB - Through an in vivo and in vitro analysis of the absorption kinetics of S-2-(3 aminopropylamino)ethylphosphorothioic acid (WR-2721) in the normal tissues and solid tumors of mice, rats, and rabbits, it has been demonstrated that normal tissues actively concentrate WR-2721 against a concentration gradient, whereas solid tumors passively absorb it, or, if active concentration of WR-2721 is present in tumors, it operates at a far reduced rate relative to normal tissues. These observations can account for the ability of WR-2721 to selectively protect normal tissues against both radiation and alkylating agent injury. PMID- 6245796 TI - Surface labeling of sialic acid residues in BHK cells and viral transformants. PMID- 6245797 TI - Epithelial cell junctions in primary and metastatic mammary tumors of mice. PMID- 6245798 TI - Effect of phenobarbital administration on hepatocytes constituting the hyperplastic nodules induced in rat liver by 3'-methyl-4-dimethylaminoazobenzene. PMID- 6245799 TI - Inhibition of prolactin-induced mammary cancer in C3Hf (XVII) mice with the trans isomer of bromotriphenylethylene. AB - C3Hf (XVII) mice never develop spontaneous mammary tumors. However, the transplantation of an isologous pituitary gland under their kidney capsule is followed by a 10-fold increase in serum and pituitary prolactin content (180 ng/ml and 20 micrograms/mg of tissue, respectively), concomitant with an increase of prolactin receptors in mammary glands. Under these conditions, mammary tumors appear in 90% of the mice. If a racemic brominated triphenylethylene, i.e., broparestrol, is administered, serum and pituitary prolactin decrease rapidly (10 ng/ml and 4 micrograms/mg of tissue, respectively), and prolactin receptors in the mammary gland are markedly reduced. This compound also inhibits the development of normal mammary glands, prevents mammary carcinogenesis, and unexpectedly causes a significant atrophy of the ovaries. Our study confirms that prolactin is a key hormone involved in murine mammary carcinogenesis and that it can act directly on the mammary gland by stimulaing the level of its own receptor. PMID- 6245800 TI - Glucose homeostasis in rats bearing a transplantable sarcoma. PMID- 6245801 TI - Effects of new antimitotic antibiotics, ansamitocins, on the growth of murine tumors in vivo and on the assembly of microtubules in vitro. PMID- 6245802 TI - Similarities between a phosphoprotein (pp60src)-associated protein kinase of Rous sarcoma virus and a cyclic adenosine 3':5'-monophosphate-independent protein kinase that phosphorylates pyruvate kinase type M2. PMID- 6245803 TI - Rapid, reversible rounding and aggregation of Rous sarcoma virus-infected chicken fibroblasts induced by a plasma macromolecule. PMID- 6245805 TI - Positive correlation between histological tumor involvement and generation of tumor cell colonies in agarose in specimens taken directly from patients with small-cell carcinoma of the lung. AB - Twenty-seven specimens for in vitro agarose clonogenicity testing were obtained from 25 patients with small-cell carcinoma of the lung (SCCL). The specimens were obtained from bone marrows, pleural effusions, lymph nodes, and liver biopsies. Colony formation was seen in 14 of 15 specimens that were histologically involved with SCCL, but no colony growth was seen in the 12 patient specimens without histocytopathological evidence of SCCL, including seven bone marrow specimens. Cytological examination of the agarose colonies confirmed their SCCL origin. Colonies reached sizes of 50 to 1000 cells in 7 to 10 days, indicating an in vitro doubling time of less than 24 hr, remarkably shorter than the population doubling times measured in patients. None of the 100 clones picked from these specimens demonstrated the ability to continuously replicate in vitro. These results show an excellent correlation between agarose colony formation and histological tumor involvement and a more rapid in vitro doubling time than that seen in vivo and demonstrate that standard tissue culture conditions do not allow demonstration of a self-renewing stem cell in fresh tumor specimens of SCCL. PMID- 6245804 TI - Effect of carcinogenic N-alkyl-N-nitroso compounds on nicotinamide adenine dinucleotide metabolism. PMID- 6245806 TI - Humoral modulation of human acute myelogenous leukemia cell growth in vitro. PMID- 6245807 TI - Activities of L-dopa decarboxylase and diamine oxidase (histaminase) in human lung cancers and decarboxylase as a marker for small (oat) cell cancer in cell culture. AB - The neuroendocrine [amine precursor uptake (decarboxylase)] properties of small (oat) cell lung cancer (SCC) have suggested that this neoplasm may have a separate histogensis from the other major types of human lung tumors. We now report that a key element of this concept, L-dopa decarboxylase activity, is present in surgical and autopsy tissues from all forms of lung cancer. Values are highest in SCC lesions; however, lung adenocarcinoma tissues can have considerable activity, and values overlap those for SCC and fall between values for SCC and large cell and squamous cell carcinoma. The distribution of diamine oxidase activity is identical except that even more overlap occurs between the major tumor types. These data may provide further evidence that SCC and other human lung cancers could share a common origin in the bronchial mucosa. In cell cuture, the distribution of the two enzyme activities is different. The average L dopa decarboxylase activity is much higher (seven separate culture lines) than in the in vivo specimens, and it completely separates these cell lines from non-SCC lung tumors (four lines). Diamine oxidase is generally low in both SCC cells and non-SCC cells in culture and does not separate the various cell types. L-Dopa decarboxylase activity thus does appear to be a valuabe marker for separating SCC cells from other lung cancer cells in vitro. PMID- 6245808 TI - Specific viral antigens in rat cells transformed by herpes simplex virus type 2 and in rat tumors induced by inoculation of transformed cells. AB - A rat cell line, RE1, oncogenically transformed by a herpes simplex virus type 2 ts mutant (ts 1), has been demonstrated to contain herpes simplex virus type 2 specific thymidine kinase activity, as have two of four tumors induced in rats by inoculation of these transformed cells. A high proportion of sera from tumor bearing rats (5 of 11) have detectable antibody against herpes simplex virus thymidine kinase, and there is a correlation between enzyme activity in a tumor and antibody in "tumor sera." A proportion of tumor sera possess neutralizing activity for herpes simplex virus infectivity. Immunfluorescence studies indicate that the transformed cells express antigens which are probably induced early in herpes simplex virus type 2-productive infection. PMID- 6245809 TI - [The presence of HLA-A2 antigens on lymphocytes - protection against tumors?]. PMID- 6245810 TI - Cytophilic binding of IgE to the macrophage. III. Involvement of cyclic GMP and calcium in macrophage activation by dimeric or aggregated rat myeloma IgE. PMID- 6245811 TI - [Effect of a mitogenic concentration on membrane glycoconjugates of human lymphocytes]. AB - Periodate oxidation of human peripheral blood lymphocytes followed by reduction with 3H labelled sodium borohydride and acidic hydrolysis generates N-AN 7, glycerol and propane 1-2 diol. This indicates that sialyl, fucosyl and probably galactosyl residues are oxidized by periodate. Neuraminidase-treated lymphocytes exhibit decreased N-AN 7 levels, increased N-AN 8 levels and increased glycerol levels. Such results were neither found with mouse splenocytes nor with calf lymph node cells. PMID- 6245812 TI - Anomalous results with the CIS-Sorin corticotropin kit. PMID- 6245813 TI - Affinity chromatography of lysosomal enzymes in plasma, urine and fibroblasts of patients with mucolipidosis (ML) II and III. PMID- 6245814 TI - Influence of inorganic phosphate on the activity determination of isoenzymes of alkaline phosphatase in various buffer systems. AB - The inhibitory effect of inorganic phosphate on the activity determination of isoenzymes of alkaline phosphatase (AP) in diethanolamine (DEA), glycine and 2 amino-2-methyl-1,3-propandiol (AMPD) buffer was studied. This effect depends on the buffer used and isoenzyme investigated. Especially the placental isoenzyme is inhibited; the inhibitory effect in DEA buffer is stronger than in the other buffers used. The requirement of purity for 4-nitrophenylphosphate with respect to its content of inorganic phosphate and conclusions for using control sera enriched with AP isoenzymes are discussed. PMID- 6245815 TI - Adenosine kinase from human erythrocytes: determination of the conditions required for assay in crude hemolystates. AB - An assay suitable for initial velocity studies was developed to measure adenosine kinase (ATP: adenosine 5'-phosphotransferase, EC 2.7.1.20) activity in crude lystaes of human erthrocytes. The pH optimum for the reaction was dependent on the ratio of Mg2+/ATP used in the assay. With a Mg2+/ATP ratio of 5.0, the pH optimum was 5.1 and only 10% of the maximal activity was retained at pH 7.3. When a Mg2+/ATP ratio of 0.50 was used, the pH optimum was 6.2, but 70% of the maximal activity was retained at pH 7.3 For assays performed at pH 7.3, the optimal Mg2+/ATP ratio was 0.50 for ATP concentrations between 0.50 and 2.0 mmol/l. Mg2+ was required for reaction, presumably to form the physiological substrate MgATP2 . However, excess free (uncomplexed) Mg2+ was a strong inhibitor of the enzyme at pH 7.3. At pH 7.3, the Km values for adenosine and MgATP2- were 0.66 mu mol/l and 82 mu mol/l respectively. PMID- 6245816 TI - Increased serum alpha-L-fucosidase and beta-N-acetylglucosaminidase activities in diabetic, cirrhotic and gastric cancer patients. AB - The activities of several glycosidases (alpha-L-fucosidase, alpha-D-mannosidase, alpha-D-galactosidase, beta-D-galactosidase, beta-N-acetylglucosaminidase and beta-D-glucuronidase) were determined in human sera from 10 normal subjects and in three groups each of 10 patients with diabetes mellitus, hepatic cirrhosis and gastric carcinoma. The results show significantly higher activities in the patients for alpha-L-fucosidase (p less than 0.001) and for beta-N acetylglucosaminidase (p less than 0.1, p less than 0.001 and p less than 0.05, respectively), and smaller or not significantly greater values for the other glycosidases. PMID- 6245817 TI - Studies on the activities, kinetic properties and subcellular localisation of cyclic AMP phosphodiesterase in human neutrophil leukocytes. AB - A one-step radioassay for cyclic AMP phosphodiesterase was optimised for human polymorphonuclear leukocytes. Kinetic studies indicated the presence of two forms of phosphodiesterase activity with apparent Km values of 0.015 mmol/l and 0.98 mmol/l for cyclic AMP. Control neutrophils were homogenised in isotonic sucrose and, after low speed centrifugation, the supernatant was subjected to analytical subcellular fractionation. Gradient fractions were assayed for principal marker enzymes and for cyclic AMP phosphodiesterase. Both forms of phosphodiesterase activity were located in the cytosol. Polymorphonuclear leukocyte homogenates were isolated from control subjects, patients with chronic granulocytic leukaemia and patients in the third trimester of pregnancy. A portion of each homogenate was used for enzyme analysis and the remainder assayed for cyclic AMP content. The specific activity (mUnits/mg protein) of the low Km phosphodiesterase was reduced in both patient groups compared with control values, whilst that of the high Km phosphodiesterase was unchanged. Leukocytes from patients with chronic granulocytic leukaemia had only a fifth of the cyclic AMP content of control neutrophils, whilst leukocytes from patients in the third trimester of pregnancy had an elevated cyclic AMP content. PMID- 6245818 TI - [Mechanism of thyroid hormone action (author's transl)]. PMID- 6245819 TI - [Hormone receptor disease (author's transl)]. PMID- 6245820 TI - [Polypeptide hormone receptor (author's transl)]. PMID- 6245821 TI - In vitro and in vivo effects of antibody to rat angiotensin converting enzyme. PMID- 6245822 TI - Cytogenetics of experimental neoplasms and non-random chromosome correlations in man. PMID- 6245823 TI - Ph1-positive leukaemia, including chronic myelogenous leukaemia. PMID- 6245824 TI - Studies on the lymphatic system in longterm survivors treated for Wilms' tumour or non-Hodgkin's lymphoma during childhood. PMID- 6245825 TI - Tumores rari et inusitati: Paget's disease of the male breast. PMID- 6245826 TI - [Electrophysiologic and morphometric studies on the peripheral nerves of rats intoxicated with methylmercury compound (author's transl)]. PMID- 6245827 TI - [A case of hypertrophic interstitial neuropathy in childhood (author's transl)]. PMID- 6245828 TI - Concentration and clearance of Tc-99m-pyridoxylidene isoleucine by a hepatoma. AB - Usually hepatic tumors show focal defects on both Tc-99m-colloid liver and Tc-99m hepatobiliary imaging. This report involves a rare case in which a hepatoma did not take up Tc-99m-phytate, but concentrated and cleared a Tc-99m-hepatobiliary agent, Tc-99m-pyridoxylidene isoleucine. PMID- 6245829 TI - Disseminated infection due to adenovirus type 4. PMID- 6245830 TI - Effect of acute methadone withdrawal on prostaglandin E-stimulated 3H-cyclic adenosine monophosphate accumulation in human platelets. AB - The effect of acute methadone withdrawal was studied on PGE1-sensitive platelet adenylate cyclase of 8 former heroin addicts who had been stabilized with methadone. During acute methadone withdrawal there was a significant increase in PGE1-sensitive platelet adenylate cyclase activity, which correlated with the severity of withdrawal symptoms. This suggests that PGE1-sensitive adenylate cyclase and cyclic adenosine monophosphate (cyclic AMP) are involved in the human addictive process. PMID- 6245831 TI - Cefotaxime kinetics after intravenous and intramuscular injection of single and multiple doses. AB - The kinetics of cefotaxime, a cephalosporin with an unusually broad antibacterial spectrum, were examined in humans after intravenous bolus injection, intravenous infusion every 6 hr for 14 days, and intramuscular injection every 8 hr for 10 days. Mean peak serum level after bolus injection of 500 mg was 37.9 microgram/ml; after 1 gm, 102.4 microgram/ml; and after 2 gm, 214.1 microgram/ml. The half-life (t1/2) was 1 hr for the 3 doses. Total serum clearance was the same for all doses. Overall excretion was 50% to 60%; part of the drug was excreted as the desacetyl derivative. After multiple intravenous infusion the elimination rate constants and t1/2 were the same on days 1 and 15. Assayable levels were present on all days 5 min before injection of a dose. Multiple intramuscular injections of 500 mg produced serum levels of 9.2 to 11.9 microgram/ml. The t1/2 was 0.93 hr. Mean serum levels at 8 hr ranged from 0.08 to 0.55 microgram/ml. Serum levels produced by intravenous infusion or intramuscular injection were inhibitory for most (90%) aerobic gram-positive and gram-negative organisms susceptible to cefotaxime. PMID- 6245832 TI - The antigonadotropic activity of Lithospermum ruderale I. The lack of steroid like activity at the receptor level. AB - Previous work has demonstrated that extracts from the plant Lithospermum ruderale have antigonadotropic activity. The possibility of steroidal substances being responsible for this activity was examined at the receptor level. It was found that only at very high concentrations of crude lithosperm extract (LS) was progesterone, testosterone, or estradiol displaced from their respective uterine receptors. Because such high doses of LS may be toxic and because they are not required for in vivo or in vitro bioactivity, it is concluded that the antigonadotropic components of Lithospermum ruderale probably do not as a steroid. PMID- 6245833 TI - The dose/response effects of gastrointestinal hormones on the opossum biliary sphincter. PMID- 6245834 TI - Achieving success in posttreatment educational placements. PMID- 6245836 TI - Etiology of type A hepatitis. PMID- 6245835 TI - Studies on the etiology of autumnal infantile acute gastroenteritis--rotavirus. PMID- 6245837 TI - Prostacyclin. PMID- 6245838 TI - [Surface charge in the region where the calcium channels of mollusk neuron somatic membrane are located]. PMID- 6245839 TI - [Production of a deletion of the central Eco RI-fragment of the DNA of prophage Mu]. PMID- 6245840 TI - [Virus specific transcription in cells transformed by SV-40]. PMID- 6245841 TI - [Specification of DNA-cytosine-methylase I (M.Eco MRE 600 I) by plasmid Col A]. PMID- 6245842 TI - [Analysis of mechanisms of post-tetanic potentiation of synaptic reactions of hippocampal pyramidal neurons]. PMID- 6245843 TI - [Functional activity of chemoreceptors following stimulation of the microtubule apparatus]. PMID- 6245844 TI - [Effect of ouabain on cholinoreceptors of giant neurons of snails]. PMID- 6245845 TI - [Activity of adenine nucleotide metabolism enzymes and adenosine deaminase in the thymus and splenic lymphocytes of rats]. PMID- 6245846 TI - The major medical sequelae of opioid addiction. PMID- 6245847 TI - [Indication for surgery in bronchial carcinoma]. PMID- 6245848 TI - [Anaplastic small cell bronchus carcinoma. Diagnosis, treatment and prognosis]. PMID- 6245849 TI - Direct inhibitory effect of gonadotropin-releasing hormone upon follicle stimulating hormone induction of luteinizing hormone receptor and aromatase activity in rat granulosa cells. PMID- 6245850 TI - Granulosa cell desensitization: effects of gonadotropin on antral and preantral follicles. PMID- 6245851 TI - Release of alpha-melanocyte-stimulating hormone from dispersed cells of the intermediate lobe of the rat pituitary gland: involvement of catecholamines and adenosine 3',5'-monophosphate. AB - Treatment of the neurointermediate lobe of the rat pituitary gland with mechanical agitation in the presence of trypsin and DNAse results in a preparation of cells which secrete alpha MSH and synthesize cAMP. The receptors for catecholamines present in the intact intermediate lobe remain functional on the dispersed cells. Thus, stimulation of a beta-adrenoceptor with (l)isoproterenol enhances the secretion of alpha MSH. This receptor is stereospecific and responds to low concentrations of isoproterenol (EC50 = 0.4 nM). Activation of a beta-adrenoceptor also increases the accumulation of cAMP. Furthermore, dopamine inhibits the basal release of alpha MSH but has no effect on basal levels of cAMP. In addition, dopamine inhibits the isoproterenol enhanced release of alpha MSH as well as the isoproterenol-induced accumulation of cAMP. PMID- 6245852 TI - Prolonged hyperprolactinemia influences beta-endorphin and Met-enkephalin in the brain. PMID- 6245853 TI - Characteristics of high affinity progesterone binding to rat placental cytosol. PMID- 6245854 TI - Polyphosphoinositides:stimulator of mitochondrial cholesterol side chain cleavage and possible identification as an adrenocorticotropin-induced, cycloheximide sensitive, cytosolic, steroidogenic factor. AB - ACTH treatment in vivo enhances the activity of adrenal cytosol for supporting pregnenolone synthesis in adrenal mitochondria. Upon fractionation of adrenal cytosol by gel filtration through Sephadex G200, pregnenolone synthesis stimulating activity is eluted just after 3H2O(Kd = 1.1--2.1). This late eluting steroidogenic activity is enhanced by ACTH treatment and diminished by cycloheximide treatment, which also inhibits adrenal protein synthesis and ACTH induced steroidogenesis. Chromatography on Sephadex G-10 yields even further separation of steroidogenic factor(s) from inactive substances; it appears that the active factor(s) adsorbs to Sephadex and that such adsorption is enhanced by a greater degree of cross-linking in the gel. The phospholipids, cardiolipin, diphosphoinositide, and triphosphoinositide, are recovered partly in adrenal cytosol and, by virtue of their polyphosphorylated head group, specifically stimulate mitochondrial pregnenolone synthesis. It seems likely that the ACTH effect on cytosolic steroidogenic activity is due to changes in polyphosphoinositides, since these phospholipids are specifically stimulated by ACTH, cycloheximide blocks the ACTH-induced increase in polyphosphoinositides, and these phospholipids comigrate with steroidogenic activity during gel filtration of adrenal cytosol. These findings along with other findings from our laboratory suggest that polyphosphoinositides may function as a cycloheximide sensitive mediator in the steroidogenic action of ACTH. PMID- 6245855 TI - Effect of increased circulating thyroid-stimulating hormone on in vitro thyroid stimulating hormone stimulation of thyroid and adipose tissues. AB - Hormones have been shown to regulate the number and/or binding properties of their own receptors. The present studies examined the effect of chronic increased endogenous TSH levels, induced by tapazole or thyroidectomy, on in vitro TSH responsiveness and binding in thyroid and adipose tissues. The results showed that TSH and prostaglandin E1 significantly increased cAMP levels in the thyroids of weight- and age-matched controls, whereas thyroids from tapazole-treated rats responded only to prostaglandin E1. Iodide organification was also measured, and the thyroids from tapazole-treated rats showed a significantly reduced effect of TSH compared to weight- and age-matched controls, although stimulation by dibutyryl cAMP was equivalent in all three groups. TSH or epinephrine stimulation of cAMP and glucose oxidation was equivalent in adipose tissue from control and hypothyroid rats. There was a significant 50% reduction in the number TSH-binding sites in thyroids from tapazole-treated rats: the affinity remained unchanged. [125I]TSH binding to adipose tissue plasma membranes was similar in control and hypothyroid groups. These studies demonstrate that elevated levels of TSH appear to regulate the number of TSH receptors in thyroid, but not adipose, tissue. PMID- 6245856 TI - Interaction of human chorionic gonadotropin and human luteinizing hormone with human thyroid membranes. AB - In an attempt to identify a possible pathogenetic role for the hCG molecule in the mechanism of the hyperthyroidism which occurs in choriocarcinoma, we have looked for evidence that the hCG molecule has a thyrotropic action on the human thyroid. The thyrotropic activity of various hCG preparations on the human thyroid was assessed by measuring the stimulation of adenylate cyclase activity in human thyroid plasma membranes purified by sucrose density gradient centrifugation. The highly purified hCG CR119 preparation stimulated human thyroid adenylate cyclase activity. Its activity was more than 654 times greater than could be accounted for by human TSH (hTSH) contamination of the preparation, as determined by RIA. The thyrotropic activity intrinsic to 1.0 IU hCG was equivalent to roughly 0.27 microU hTSH. Significant saturable binding of the 125I labeled highly purified hCG preparation to human thyroid membranes was demonstrated, and the bound component was characterized. Its apparent molecular size, subunit composition, and testis receptor-binding characteristics were those of the hCG molecule. Examination of a crude urinary hCG preparation in adenylate cyclase and TSH radioligand assays using human thyroid membranes showed no evidence of any molecule other than hCG with a thyrotropic action on the human thyroid. Given that hCG binds to and stimulates adenylate cyclase activity in human thyroid tissue, as the above data indicate, then human LH (hLH) would be expected to do the same, since hLH and hCG have such strong structural and functional similarities. As anticipated, a highly purified hLH preparation exhibited TSH binding inhibition and adenylate cyclase stimulation. Its activity was more than 1030 times greater than could be accounted for by hTSH contamination of the preparation. The thyrotropic activity intrinsic to 1.0 IU hLH was equivalent to roughly 44 microU hTSH. Thus, in addition to other shared properties, the hLH molecule and the hCG molecule share the ability to interact with human thyroid tissue. These results strongly indicate that the hCG molecule has a thyrotropic action on the human thyroid and support the hypothesis that hCG is the thyrotropic factor that mediates the hyperthyroidism which occurs in patients with hCG-secreting neoplasms. PMID- 6245857 TI - Properties of angiotensin II receptors of isolated rat glomeruli: factors influencing binding affinity and comparative binding of angiotensin analogs. PMID- 6245858 TI - Lactogenic and somatotropic binding sites in liver membranes of rats with renal insufficiency. AB - Binding sites for human GH (hGH) were studied in liver membranes of rats with chronic renal insufficiency (CRI) associated with marked growth retardation. A subtotal nephrectomy was performed in young female rats. One month after the nephrectomy, the animals with a plasma creatinine level 3 times or more that of controls were studied; their mean statural gain was 56% that of controls. The specific binding of [125I]hGH to microsomal membranes of rats with CRI was low (40% that of controls). The number of binding sites rather than the affinity of the binding was affected; both the lactogenic and somatotropic sites were decreased, as judged from the binding of ovine [125I]PRL and bovine [125I]GH. The binding sites of the plasma membranes as well as those of the Golgi fractions, were reduced. In plasma membranes of rats with CRI, the specific binding of glucagon was low, and the specific binding of insulin was elevated; these modifications were associated with a high plasma glucagon level and a decreased insulinemia in rats with CRI, but no modification of plasma GH and PRL levels was found. Thus, the hormone level does not appear to regulate the GH-binding sites in this system. The link between the growth defect and the decreased number of GH binding sites in the liver membranes of rats with CRI remains to be established. PMID- 6245859 TI - In vitro studies of the adenosine 3',5'-monophosphate (cAMP) response of embryonic rat calvaria to bovine parathyroid hormone-(1--84) [bPTH-(1--84)], BPTH (1--34), and bPTH-(3--34) and the loss of cAMP responsiveness after prolonged incubation. PMID- 6245860 TI - Gonadotropin receptors in rat during altered testicular function. AB - Specific testicular binding of 125I-HCG and plasma levels of testosterone are decreased in rats three weeks after hypophysectomy or adrenalectomy plus thyroidectomy but they are not changed after adrenalectomy or thyroidectomy. The affinity of gonadotropin receptors to HCG is not altered. PMID- 6245861 TI - The effect of physiological doses of thyroxine on the level of cyclic adenosine 3',5'-monophosphate in pituitary and anterior hypothalamus of male rats of different age. AB - The levels of cAMP in the pituitary and anterior hypothalamus were determined by competitive binding to protein in male rats aged 2--2.5, 6--8 and 14--18 months. The lowest level of cAMP both in the pituitary and anterior hypothalamus (1.05 +/ 0.17 and 0.85 +/- 0.23 pM) (per mg wet weight, respectively) was found in 6--8 month-old rats. Administration of T4 (2 micrograms/100 g body weight, for 8 days) was followed by a decrease in cAMP level in the pituitary of 14--18 month-old animals, which was not the case with younger rats. The obtained results agree with the earlier observation that the threshold to homeostatic suppression in the hypothalamus-pituitary-thyroid system of rats decreases with aging. It is suggested that cAMP system contributes to the mechanism of changes in hypothalamic threshold and its pharmacological correction. PMID- 6245862 TI - Calciotropic hormones and lipolysis of human adipose tissue: role of extracellular calcium as conditioning but not regulating factor. AB - The influences of different calcium concentrations (0, 0.924 and 2.772 mMol/l) on lipolysis of in vitro incubated human adipose tissue slices or adipocytes were studied under the conditions of stimulation with isoproterenol and parathyroid hormone preparations or inhibition by insulin. Extractive bovine PTH (as well as synthetic PTH 1--34) stimulated glycerol release in a biphasic pattern similarly to isoproterenol; PTH was about half as potent as isoproterenol. The optimal conditions for lipolysis were observed using a calcium concentration of 0.924 mMol/l, whereas lipolysis was distinctly impaired at concentrations of 0 or 2.772 mMol/l; this was true for basal as well as isoproterenol- and PTH stimulated lipolysis or the inhibitory effect of insulin. In contrast to partially purified extractive calcitonin, pure synthetic calcitonin did not inhibit lipolysis. Isoproterenol- and PTH-administrations led to cAMP accumulation in the adipose tissue, this process was also diminished at the non-optimal calcium concentrations. The results suggest a conditioning, but not a regulating significance of extracellular calcium for lipolysis, whereas the importance of the lipolytic potency of PTH remains to be elucidated. PMID- 6245863 TI - Effect of substrate supply and beta-adrenergic blockade on heart glycogen and triglyceride utilization during exercise in the rat. AB - Exercise-induced heart glycogen and triglyceride mobilization was studied in control rats, in rats with reduced blood glycose supply (fasted rats), in rats with reduced plasma free fatty acids (FFA) supply (nicotinic acid-treated rats), and in rats with blockade of beta-adrenergic receptors (propranolol-treated rats). It was found in the fed control rats that both the heart glycogen and triglyceride levels were reduced at the beginning of the exercise and thereafter they returned to the control level despite the exercise being continued. The triglyceride level was reduced again during the exhaustive exercise. Reduced blood glucose supply increased the heart glycogen and triglyceride utilization during exercise. Partial prevention of the plasma FFA elevation during exercise increased the heart glycogen utilization and had no effect on utilization of the heart triglycerides. Blockade of the beta-adrenergic receptors fully prevented both the heart glycogen and triglyceride mobilization during exercise. PMID- 6245864 TI - The interaction of the EcoRI restriction endonuclease with its substrate. A physico-chemical study employing natural and synthetic oligonucleotides and polynucleotides. PMID- 6245865 TI - Glycogen-synthase phosphatase activity in rat liver. Two protein components and their requirement for the activation of different types of substrate. AB - Three subfractions of glycogen synthase b (termed b1, b2, b3) have been isolated from the glycogen fraction of dog liver on the basis of a different affinity for DEAE-cellulose. Their kinetic properties and chromatographic behaviour are compatible with the presence of an increasing number of phosphorylated sites from synthase b1 towards b3. Synthase phosphatase activity in rat liver stems from two heat-labile and trypsin-labile proteins. These components are conveniently prepared from the cytosolic fraction of glycogen-depleted liver; the 'G component' of the phosphatase co-sediments with added particulate glycogen, whereas the 'S-component' remains in the supernatant. The G-component alone did not convert any available synthase b to the a form. The synthase phosphatase activity of the S-component was variable according to the actual type of substrate. When acting on synthase b2 and b3, the S-component had a low phosphatase activity that was increased 7-fold and 11-fold, respectively, upon addition of the G-component. Synthase b1, however, was efficiently activated by the S-component, and only 35% faster in the presence of both components. When the cytosolic fraction of glycogen-depleted livers was analysed by sucrose-gradient centrifugation a single peak of phosphatase activity (S20, W = 10.2 S; provisional Mr = 254000) was detected with synthase b2 as substrate. In addition to this peak, presumably an S-G complex, synthase b1 also identified free S component of lower and heterogeneous molecular weight. Our results illustrate in general the influence of the type of synthase b on the detection of synthase phosphatase activity, and specifically may provide an explanation for some discrepant reports on the subcellular distribution of the enzyme. PMID- 6245866 TI - Macrophage factor that induces neutral protease secretion by normal rabbit chondrocytes. Studies of some properties and effects on metabolism of chondrocytes. AB - Normal rabbit-articular chondrocytes secrete very small amounts of degradative enzymes in culture. Rabbit peritoneal macrophages, when activated with lipopolysaccharides, release a factor in the medium which stimulates the chondrocytes to produce significantly high levels of collagenase and other neutral protease for 2-3 days. The soluble mediator from macrophages appears to be a polypeptide with a molecular weight of 13000-15000 and can be inactivated by short-term treatment with trypsin or pronase. The enzyme-synthesis by chondrocytes can be stimulated to the same extent by repeated addition of the macrophage-medium. The metabolism of chondrocytes is altered due to the presence of this mediator. The cellular proliferation is diminished, while the rates of degradation as well as biosynthesis of the matrix are increased. These studies suggest the possibility that in the conditions such as osteoarthritis, where the synovial cells may not play an active role in cartilage degradation, the proteases can be produced by the cartilage cells themselves after the stimulation by macrophage-derived mediators. These intrinsic enzymes may be responsible for the slow, but progressive degeneration of cartilage tissue. PMID- 6245867 TI - The role of calcium and guanosine 3':5'-monophosphate in the action of acetylcholine on thyroid metabolism. AB - The role of calcium and guanosine 3':5'-monophosphate (cyclic GMP) in the regulation of thyroid metabolism has been investigated in dog thyroid slices. Carbamoylcholine enhanced glucose carbon-1 oxidation, protein iodination, cyclic GMP accumulation and decreased thyrotropin-induced adenosine 3':5'-monophosphate (cyclic AMP) accumulation and iodine secretion; it did not affect protein synthesis. The effects of carbamoylcholine were reproduced under various experimental conditions by supplementary calcium in the medium, ouabain, and in media in which Na+ had been replaced by choline chloride. They were inhibited by lanthanum. These results further support the hypothesis that free intracellular Ca2+ is the intracellular signal for carbamoylcholine effects and suggest that a Na+ -gradient-driven Ca2+ extrusion mechanism operates in the thyroid cell. Mn2+ reproduced the effect of Ca2+ on glucose oxidation, protein iodination and cyclic GMP accumulation in Ca2+ -depleted slices and medium, and thus mimicked some intracellular effects of Ca2+. On the other hand Mn2+ inhibited the carbamoylcholine effect on thyrotropin-induced thyroid secretion and cyclic AMP accumulation, and Ca2+ inhibited the Mn2+-induced cyclic GMP accumulation. This suggests that the two ions compete for the same channel. Similarly Mn2+ inhibited calcium effects in the presence of ionophore A23187. Procaine inhibited protein iodination under all conditions suggesting a primary effect; it also inhibited all carbamoylcholine and ouabain actions. However the drug did not inhibit the effects of choline chloride and its action was reversed by raising carbamoylcholine but not Ca2+ concentration; it is therefore doubtful that procaine acts by blocking Ca2+ channels. In media without added Ca2+, Mn2+ increased cyclic GMP accumulation but did not decrease thyrotropin-induced cyclic AMP accumulation or iodine secretion, which suggests that cyclic GMP cannot be the sole mediator of the latter two effects of carbamoylcholine. PMID- 6245869 TI - Interpretation of the Mossbauer spectra of the high-potential iron protein from Chromatium. PMID- 6245868 TI - ADP-ribosylation of nuclear proteins in normal lymphocytes and in low-grade malignant non-Hodgkin lymphoma cells. AB - Normal lymphocytes and lymphocytes from patients with low-grade malignant non Hodgkin lymphoma were isolated from blood by a Percoll gradient procedure. Absence of cell proliferation in both cell types was indicated by very low [3H]thymidine incorporation rates. Determination of endogenous protein-bound single ADP-ribose residues by a radioimmunoassay revealed that the leukemic cells had 2.5-times lower levels of the NH2OH-sensitive and a 4-fold lower amount of NH2OH-resistant ADP-ribose . protein conjugate subfractions, respectively, than normal lymphocytes. By contrast, "total" ADP-ribose transferase activity, as measured in homogenates or permeabilized cells in the presence of DNase, was two times higher in leukemic cells, whereas activity determined in permeabilized cells in the absence of added DNase was practically identical in both cell types. The apparent discrepancy between ADP-ribose transferase activity and endogenous levels of protein-bound single ADP-ribose residues may be explained in part by an enzyme inhibitor present in normal human lymphocytes. NAD + NADH levels were decreased 2.5-fold in the leukemic cells. This decrease, however, does not explain the reduced levels of mono(ADP-ribose) . protein conjugates since the ratio of protein-bound single ADP-ribose residues to NAD is distinctly different in leukemic lymphocytes compared to normal lymphocytes. PMID- 6245870 TI - Characterization of horse thyroid cyclic nucleotide phosphodiesterases. PMID- 6245871 TI - A new method for the purification of DNA-binding proteins with sequence specificity. AB - We describe a technique for a rapid and efficient isolation and purification of proteins binding to defined DNA sequences. Cloned double-stranded DNA was covalently coupled to m-aminobenzyloximethylcellulose in order to purify proteins which recognize and bind to specific sequences on the DNA. The purification of two DNA-binding proteins from Drosophila melanogaster is demonstrated using the respective cloned DNA sequences. PMID- 6245872 TI - Chloroplast phosphoproteins. Evidence for a thylakoid-bound phosphoprotein phosphatase. AB - 1. Isolated intact pea (Pisum sativum) chloroplasts incorporate [32P]orthophosphate into several thylakoid polypeptides in the light. Transfer of the labelled chloroplasts to darkness results in rapid dephosphorylation of the polypeptides. The most rapidly dephosphorylated phosphoproteins are the 26000-Mr doublet derived from the light-harvesting chlorophyll a/b binding complex. 2. Incubation of isolated 32P-labelled thylakoids in buffer in the absence of stromal components also results in rapid protein dephosphorylation. Again, the most rapidly dephosphorylated phosphoproteins are the 26000-Mr light-harvesting doublet. Dephosphorylation of all thylakoid phosphoproteins is accelerated by addition of up to 10 mM MgCl2. 3. The enzyme responsible for dephosphorylation is a phosphatase rather than a phosphotransferase or the thylakoid protein kinase acting in reverse. The enzyme is specifically and totally inhibited by NaF and does not require phosphoryl group acceptors such as ADP. Unlike the protein kinase, the phosphatase is indifferent to light and the electron transport inhibitor 3(3,4-dichlorophenyl)-1,1-dimethylurea. 4. The phosphorylated regions of the thylakoid phosphoproteins protrude from the outer surface of the membrane and are removed by trypsin treatment. PMID- 6245873 TI - Phosphoenolpyruvate carboxykinase in cultured foetal hepatocytes from the rat. Ontogeny of hormone inducibility and role of glucocorticoids and insulin in enzyme induction. PMID- 6245874 TI - Isolation of a complex between the P protein of phage lambda and the dnaB protein of Escherichia coli. AB - P protein of phage lambda and dnaB protein of Escherichia coli were isolated from (a) bacteria containing an inducible lambda P gene on a plasmid, and (b) phage lambda-infected bacteria. P protein from both sources copurifies with part of the dnaB protein during four purification steps. A highly purified preparation contains the multimeric dnaB and the P protein in a complex as revealed by glycerol gradient centrifugation. The complex is composed of two major polypeptides. Their molecular weights of 52 000 and 26 000 are identical to those previously determined for the dnaB and P polypeptides, respectively. The complex contains a DNA-dependent ribonucleoside triphosphatase activity which can be inactivated by anti-dnaB globulin. Both the dnaB complementing and the ribonucleoside triphosphatase activities are partially masked by the P protein as shown by their stimulation following a treatment with sodium chloride and N ethylmaleimide. PMID- 6245875 TI - Degradation of linear and circular DNA with gaps by the recBC enzyme of Escherichia coli. Effects of gap length and the presence of cell-free extracts. AB - It is shown that circular PM2 DNA with two gaps of 13 nucleotides per molecule is degraded by purified recBC enzyme from Escherichia coli to acid-soluble material at a rate which is less than one tenth of the rate of solubilization of linear duplex DNA. Increasing the gap length in the circular DNA to 40-650 nucleotides does not affect the breakdown of the molecules by the recBC enzyme, nor does it change the proportions of the products formed (acid-soluble material, acid insoluble fragments and non-degraded molecules). On the other hand, terminal gaps in linear duplex DNA produced by limited digestion with either exonuclease III or lambda exonuclease significantly reduce the rate of the degradation by the recBC enzyme, particularly when the gaps exceed 100 nucleotides. The results suggest that the recBC enzyme does not cleave gaps in circular DNA at random positions, but possibly at the junction between single-stranded and duplex DNA or close to it. The degradation of gapped circular DNA by purified recBC enzyme was used to search for an inhibitor of the recBC enzyme in extracts from ultraviolet irradiated cells. No such inhibitor has been observed but rather a weak stimulatory factor for the solubilization of gapped circular DNA by the recBC enzyme. Thus, the experimental system appears not to be suited as a test in vitro for an ultraviolet-induced inhibitor of the recBC enzyme which has been postulated to be produced in recA+ lexA+ cells of E. coli after ultraviolet irradiation. PMID- 6245876 TI - Subcellular fractionation of Trypanosoma brucei bloodstream forms with special reference to hydrolases. AB - Bloodstream forms of Trypanosoma brucei have been screened for the presence of enzymes that could serve as markers for the plasma membrane, flagellar pocket, lysosomes, endoplasmic reticulum and Golgi apparatus in order to study the subcellular organization of the digestive system of the parasite. Acetylesterase, acid DNase, acid phosphatase, acid phosphodiesterase, acid proteinase, acid RNase, alanine aminotransferase, galactosyl transferase, alpha-glucosidase, inosine diphosphatase and alpha-mannosidase were partially characterized and their assays optimized for pH-dependent activity, linearity of reaction with respect to incubation time and enzyme concentration, and the effect of inhibitors and activators. The association of these enzymes with particulate material and the presence of structural latency were investigated. Acid proteinase and alpha mannosidase are particle-bound and latent in cytoplasmic extracts; they can be activated and solubilized in part by Triton X-100. Similar results were obtained for acid phosphatase, acid phosphodiesterase and inosine diphosphatase. Neutral alpha-glucosidase, though partly sedimentable, does not show latency and is readily solubilized by the detergent. Galactosyl transferase is firmly membrane bound even in the presence of 0.1% Triton X-100. Cell fractionation by differential centrifugation and density equilibration on sucrose gradients revealed that both alpha-mannosidase and acid proteinase are associated with organelles that band at a density of about 1.20 g/cm3. Inosine diphosphatase, galactosyl transferase, acid phosphatase and acid phosphodiesterase sediment predominantly as microsomal constituents equilibrating at densities between 1.13 and 1.15 g/cm3. In addition, inosine diphosphatase and galactosyl transferase exhibit considerable activity at higher densities (1.18-1.25 g/cm3). Neutral alpha-glucosidase is mainly recovered in the nuclear and microsomal fraction; its particulate part equilibrates as a single band at rho = 1.22 g/cm3. Acetylesterase and acid DNase are largely soluble, whereas acid RNase does not produce distinct sedimentation and banding profiles. In intact cells, neutral alpha-glucosidase and acid phosphatase appear to be highly accessible to their substrates. It is tentatively concluded that (a) acid proteinase and alpha mannosidase are lysosomal enzymes, (b) acid phosphatase and acid phosphodiesterase are associated with the flagellar pocket and part of the former enzyme probably with the endoplasmic reticulum, (c) galactosyl transferase is a constituent of the Golgi apparatus, and (d) alpha-glucosidase may serve as a marker for the plasma membrane. Inosine diphosphatase may also be derived from the latter structure. PMID- 6245877 TI - Studies of photochemical action spectra on N,N,N',N'-tetramethyl-p phenylenediamine-oxidase-negative mutants of Azotobacter vinelandii. PMID- 6245878 TI - Increased sensitivity to lipolytic hormones of adenylate cyclase in fat cells of diabetic rats. PMID- 6245879 TI - The regulation of glycogen metabolism. Purification and properties of protein phosphatase inhibitor-2 from rabbit skeletal muscle. PMID- 6245880 TI - A DNA-binding protein specific for the early replicated region of the chromosome obtained from Escherichia coli membrane fractions. AB - After extensive dialysis of Escherichia coli membranes treated with Triton X-100, three membrane proteins (A, B and B') with an affinity for DNA have been isolated and purified. They bind to either double-stranded or single-stranded DNA. A and B' proteins preferentially attach to DNA even in the presence of poly(uridylic acid). Only protein B' can recognize some base sequence of DNA because pulse labelled DNA made at the initiation of replication in a synchronized dnaC mutant has been selectively retained by the protein. PMID- 6245882 TI - ATP:AMP phosphotransferase from baker's yeast. Purification and properties. AB - An improved homogeneous preparation of adenylate kinase (ATP:AMP phosphotransferase, ATP + AMP in equilibrium 2 ADP) from baker's yeast was attained by extraction using ethyl acetate and successive column chromatography on Affi-Gel blue, Sephadex G-100, phosphocellulose and Sephacryl S-200. The overall purification is about 670-fold with a yield of 23% and final specific activity of 1900 units/mg protein. The enzyme preparation is a single band in isoelectrofocusing with a pI of 5.7. By sodium dodecyl sulfate gel electrophoresis and gel chromatography the molecular weight is 27 500. Among the nucleoside monophosphates investigated (AMP, CMP, GMP, IMP and UMP) only AMP reacts with ATP (dATP). ATP (dATP) is about one order of magnitude more active than CTP, GTP, ITP and UTP. The enzyme catalyzes only in the presence of a divalent metal cation, namely Mg2+, Ca2+, Co2+, Mn2+ and Ni2+, and the reaction rate is maximal at about 0.5 M NaCl. The binding of the substrates also takes place in the absence of metal. The dissociation constants for ATP, MgATP, CTP, GTP, UTP and AMP are 3.4, 4.2, 18.5, 17.2, 23.8 and 39.3 microM respectively. The amino acid composition of the purified enzyme is: 32 aspartic acid + asparagine, 12 threonine, 12 serine, 27 glutamic acid + glutamine, 16 proline, 21 glycine, 24 alanine, 11 valine, 9 methionine, 17 isoleucine, 25 leucine, 4 tyrosine, 7 phenylalanine, 2 half-cystine (no free sulfhydryl), 23 lysine, 6 histidine, 10 arginine and 2 tryptophan, totalling 260 residues. PMID- 6245881 TI - Phosphorylation in vitro of membrane fragments from Torpedo marmorata electric organ. Effect on membrane solubilization by detergents. AB - Acetylcholine receptor-rich membrane fragments purified from Torpedo marmorata electric organ were phosphorylated, in vitro, by endogenous protein kinases. The 40 000-Mr chain, which carries the acetylcholine receptor site, was never labelled; on the other hand, protein bands of apparent molecular weights 43 000, 50 000 and 66 000, which are present in the acetylcholine receptor-rich membranes, were repeatedly phosphorylated. The phosphorylation of these three peptides required the presence of divalent cations, such as Mg2+ or Mn2+, and was, in addition, stimulated up to 3--5-fold by K+. The effect of Na+ ions appeared less specific since Na+ ions reduced the labelling of all the polypeptides susceptible to phosphorylation. Cholinergic agonists and antagonists, local anesthetics and cyclic nucleotides did not affect the phosphorylation of the receptor-rich membranes. Phosphorylation selectively modified the solubilization of several polypeptides by nondenaturing detergents: phosphorylated 43 000-Mr, 50 000-Mr and 66 000-Mr polypeptides were solubilized at lower concentrations of detergent than their non-phosphorylated counterparts. Two-dimensional gels revealed the existence of a charge heterogeneity of the 40 000-Mr and 43 000-Mr chains. The microheterogeneity of the 43 000-Mr chain, but not that of the 40 000-Mr chain, might result from a selective phosphorylation of this particular chain. PMID- 6245883 TI - The subunit composition of mammalian cytochrome c oxidase. AB - Cytochrome c oxidase from rat liver mitochondria was separated into 12 different protein subunits by application of a highly resolving sodium dodecylsulfate/gel electrophoretic system of different compositions. The 12 protein subunits are shown to represent integral components of mammalian type cytochrome c oxidase for the following reasons. 1. All 12 subunits copurify through various purification procedures. 2. The subunit composition of the isolated enzyme is identical to that of the immunoprecipitated one. 3. All 12 subunits are present in the complex at one to one stoichiometric amounts. 4. A similar composition of 12 subunits was also found for cytochrome c oxidase from rat kidney, pig heart, rabbit liver and stone-marten liver. The difference between our results and all other published data on the subunit composition of mammalian-type cytochrome c oxidase, based on gel electrophoretic analysis, is due to the insufficient resolving power of previously used gel systems and the very similar molecular weight of subunits VIa, b, c, and VIIa, b, c. PMID- 6245884 TI - The enhancement of cytotoxicity of N-methyl-N-nitrosourea and of gamma-radiation by inhibitors of poly(ADP-ribose) polymerase. AB - Inhibitors of poly(ADP-ribose) polymerase show a synergistic potentiation of cytotoxicity with certain DNA-damaging agents. Non-toxic concentrations of 5 methylnicotinamide dramatically potentiate the cytotoxicity of N-methyl-N nitrosourea as tested by the cloning ability of mouse leukaemia (L1210) cells. A dose-enhancement factor of about 10 is observed. This potentiation is dependent on the concentration of 5-methylnicotinamide. The methylxanthines theobromine, theophylline and caffeine also increase the cytotoxicity of methylnitrosourea. Thymidine, in the presence of sufficient deoxycytidine to overcome the perturbation of deoxynucleotide metabolism, also potentiates the cytotoxicity of methylnitrosourea. Nicotinate, which is not an inhibitor of poly-(ADP-ribose) polymerase, has no effect on methylnitrosourea toxicity. A very small, but consistent, enhancement of the toxicity of gamma-radiation by the same inhibitors has been observed. We suggest that this potentiation of cytotoxicity is mediated by inhibition of (ADP-ribose)n biosynthesis; and that the biosynthesis is stimulated by DNA damage. We therefore propose that (ADP-ribose)n takes part in cellular repair mechanisms, either by modifying chromatin structure or by a specific participation in DNA repair. PMID- 6245885 TI - The reaction of bovine pancreatic ribonuclease A with 6-chloropurineriboside 5' monophosphate. Evidence on the existence of a phosphate-binding sub-site. AB - The chemical modification of bovine pancreatic ribonuclease A by 6-chloropurine 9 beta-D-ribofuranosyl 5'-monophosphate was studied under several reaction conditions. The reaction, at pH 7.3, 40 degrees C and a nucleotide: enzyme molar ratio of 60, showed a high degree of specificity in comparison to those corresponding to the base or the nucleoside. The main derivative was isolated by means of CM-cellulose chromatography. Subtilisin cleavage of this derivative showed that the substitution had taken place in the S-peptide moiety. Tryptic digestion of the S-peptide indicated that a lysine residue had been modified. Enzymatic and physico-chemical considerations showed that the actual site of reaction was the alpha-amino group of Lys-1. The structural and kinetic properties of the derivative are consistent with the existence of a phosphate binding sub-site near the N-terminal region of the enzyme. PMID- 6245886 TI - A proton-magnetic-resonance study of N-trifluoroacetyl-L-alanyl-L-phenylalaninal binding to alpha-chymotrypsin. AB - Cross-saturation NMR studies have shown that the dipeptide aldehyde N trifluoroacetyl-L-alanyl-L-phenylalaninal forms a hemiacetal complex with alpha chymotrypsin. The free aldehyde resonance was seen to broaden upon addition of alpha-chymotrypsin and a detailed analysis has identified the enzyme-bound hemiacetal as the species which was in slow exchange with the free aldehyde and so gave rise to the perturbation. The line broadening was found to be dependent on p2H and this behaviour could be adequately described by the ionisation of a single group on the free enzyme (pKa2H7.6) with the alkaline form being required for hemiacetal formation. The pH dependence of alpha-chymotrypsin-induced catalysis around neutral pH correlates well with the observed p2H dependence of hemiacetal formation, indicating that it is an intermediate in the catalytic mechanism. PMID- 6245887 TI - High variability of the electron carrier plastocyanin in microalgae. AB - 1. The plastocyanin content of Scenedesmus can be dramatically varied with the copper content of the culture medium. Figures as high as 7 mmol plastocyanin/mol chlorophyll are possible. Electron paramagnetic resonance (EPR) spectroscopy has been used to determine this physiological response quantitatively in intact cells having different amounts of plastocyanin. The results obtained by the EPR technique were compared with data on isolated plastocyanin determined either by spectrophotometry or immunoelectrophoresis. Agreement was found for the amount of plastocyanin detected by the first two methods, whereas the last assay yielded data at least 25% higher on the average. Under all culture conditions a copper free plastocyanin precursor is present. 2. The EPR properties of purified plastocyanin and those of cellular plastocyanin located within the thylakoids are practically identical in terms of g-values, hyperfine splittings, signal linewidths and saturation behavior at temperatures of 12--15 K. Our data indicate that plastocyanin is not present in a membrane-bound form but exists as a single soluble pool. 3. The studies have been extended to the algae Dunaliella parva and Bumilleriopsis filiformis. The first species exhibits a limited variation of plastocyanin with the copper content of the medium. Furthermore, no cytochrome c 553 could be detected in Dunaliella even under conditions of copper deficiency. In contrast, Bumilleriopsis does not contain plastocyanin regardless of the amount of copper offered. PMID- 6245888 TI - Expression of mammary tumour virus in late-appearing mammary carcinomas in presumed virus-free mice. PMID- 6245889 TI - Suppression and reappearance of N-tropic L virus production in somatic cell hybrids after introduction and loss of chromosomes carrying Fv-1b. PMID- 6245890 TI - Genetics of resistance to lymphoma development in crosses between CBA and AKR strains. PMID- 6245891 TI - Cyclic AMP production in isolated colonic epithelial crypts: a highly sensitive model for the evaluation of vasoactive intestinal peptide action in human intestine. PMID- 6245892 TI - Plasma cyclic nucleotide responses to insulin-induced hypoglycaemia and methacholine in patients with hyperthyroidism. AB - The effect of insulin-induced hypoglycaemia and methacholine on plasma cAMP and cGMP levels was studied in normal volunteers, hyperthyroid and hypothyroid patients. A significant positive correlation existed between the maximal increase in plasma cAMP and the maximal decrease in plasma glucose in normals during insulin-induced hypoglycaemia. Therefore, the plasma cAMP response is considered to be dependent on the degree of hypoglycaemia, rather than the dose of insulin. The cAMP response to hypoglycaemia was significantly higher in hyperthyroid patient, and was lower in patients with hypothyroidism than in normals. The cAMP response of the hyperthyroid patients was normalized when their hyperthyroidism was controlled after 3 months of treatment. The plasma level of cGMP was slightly elevated during hypoglycaemia, but there was no significant difference between controls and hyperthyroid patients. The cGMP response to methacholine, which is probably mediated by cholinergic receptors, was significantly potentiated in hyperthyroid patients. The cAMP response, which is presumably dependent on endogenous catecholamines secreted during methacholine-induced hypotension, was also enhanced in hyperthyroid patients. It is likely that beta-adrenergic receptor responses and cholinergic receptor responses are both enhanced in hyperthyroidism. PMID- 6245893 TI - Prostaglandin (PG) release in the mixed lymphocyte culture; effect of presensitization by a skin allograft; nature of the PG-producing cell. PMID- 6245894 TI - Failure of ketamine to interact with opiate receptors. AB - Ketamine, an anesthetic agent endowed with several morphine-like effects, failed to displace 3H-dihydromorphine or 3H-methionine-enkephalin from opiate receptors in the rat brain synaptosomal-mitochondrial membrane preparations. Furthermore, ketamine-induced analgesia in rats was not antagonized by naloxone, suggesting that this effect is not mediated by opiate receptors. PMID- 6245895 TI - alpha-Adrenoceptors in rat brain: sodium changes the affinity of agonists for prazosin sites. PMID- 6245896 TI - Carticaine: action of the local anesthetic on myelinated nerve fibres. AB - Unlike other clinically used local anesthetics, carticaine contains a thiophene ring. Current voltage relations of peak sodium current INa and steady state potassium current IK were measured in voltage clamp experiments on the node of Ranvier of Rana esculenta. The dependence of the maximum sodium conductance on external concnetration of carticaine is described by an apparent dissociation constant KNa = 0.065 mM at pH = 7.3. An apparent dissociation constant KK = 0.147 mM at pH = 7.3 was calculated on the basis of the action of carticaine on the maximum potassium conductance. Similar to other amine local anesthetics, carticaine blocks sodium channels at a lower concentration than potassium channels, but lower concentrations of the thiophene derivative than of the benzene derivatives are needed to block the ionic channels. The partition coefficients in-octanol/Soerensen buffer at pH = 7.35 follow the sequence lidocaine (46) more than carticaine (17) more than procaine (2). Therefore, the action of these local anesthetics on sodium channels and potassium channels seems not to follow mere lipid solubility properties of the neutral drug. Increasing the pH from 6.3 to 8.3 favoured the neutral drug form and enhanced the block of both ionic channels but the relative reduction of the ionic currents was larger for potassium currents. PMID- 6245897 TI - Effects of captopril (SQ 14, 225) on the renin-angiotensin-aldosterone system in normal rats. AB - High doses of captopril (SQ 14, 225) (120-160 mg/kg/day) were administered orally to normal rats, and the effects on the renin-angiotensin-aldosterone system were observed. Plasma angiotensin converting enzyme (ACE) activity was elevated significantly on the 3rd, 7th and 30th days of captopril administration. ACE activity in the lung and the kidney was significantly decreased on the 1st day then gradually increased, becoming significantly higher than that of controls by the 30th day. Plasma renin activity (PRA) was significantly elevated on the 1st day and remained at a high level until the 30th day. Renal renin content was found to be significantly lower on the 1st and 3rd days. Plasma aldosterone concentration was not affected by captopril treatment, whereas serum potassium concentration was found to be significantly lower on the 1st, 3rd and 30th days. It is suggested that besides its inhibitory action on ACE, captopril has a direct or indirect stimulating action on ACE production as well as on renin release. PMID- 6245898 TI - Binding of an imidazolidine (clonidine), an oxazoloazepin (B-HT 933) and a thiazoloazepin (B-HT 920) to rat brain alpha-adrenoceptors and relation to cardiovascular effects. AB - The specific binding to alpha-adrenoceptors in crude plasma membrane preparations of the rat brain was studied by means of 3H-clonidine (specific radioactivity 26.7 Ci/mmole). Equilibrium binding of 3H-clonidine could be described adequately according to a two-site model with a minor population of high affinity sites (KD1 = 0.4 nM) and a major population of low affinity sites (KD2 = 6.1 nM). The heterogeneity of 3H-clonidine binding was also indicated by a biphasic association rate in kinetic binding studies. In competition experiments with 3H clonidine concentrations of 0.5 or 4.0 nM respectively, concentration-dependent displacement was observed with the non-radioactive compounds: clonidine, B-HT 920 (2-amino-6-allyl-5, 6, 7, 8-tetrahydro-4H-thiazolo-[5, 4-d]-azepin dehydrochloride) and B-HT 933 (2-amino-6-ethyl-4, 5, 7, 8-tetrahydro-6H-oxazolo [5, 4-d]-azepin-dihydrochloride). IC50 values of 3, 21 and 160 nM or 10, 63 and 380 nM respectively were thereby evaluated. Cardiovascular effects were estimated in rats. The blood pressure increase in spinal animals was taken as parameter for alpha-adrenoceptor stimulation at peripheral vascular sites. The bradycardic effect in vagotomized animals was taken as parameter for central nervous sympathoinhibition. The ranking order of the potency of the three drugs was the same in both in vivo tests and parallels the in vitro binding affinities at both binding sites: clonidine greater than B-HT 920 greater than B-HT 933. These results indicate the similarity of the alpha-adrenoceptor structures in brain membrane preparations, at peripheral vascular sites and at central sympathoinhibitory sites. PMID- 6245899 TI - Rapid desensitization of cerebral cortical beta-adrenergic receptors induced by desmethylimipramine and phenoxybenzamine. PMID- 6245900 TI - Excitation of units in the lateral geniculate and contiguous nuclei of the cat by stretch of extrinsic ocular muscles. AB - In cats, anaesthetized with chloralose and paralysed, the responses of units in the right lateral thalamus were recorded while the extrinsic ocular muscles (EOM) of the right eye were stretched in the dark. Phasic responses were found in all layers of the dorsal lateral geniculate nucleus (LGNd) and in the perigeniculate nucleus (PGN). A given unit usually responded to stretch of more than one EOM and thus to more than one direction of rotation of the eye in the orbit. LGNd. Of a sample of 76 units in LGNd, 55 (72%) gave visula but no muscle responses and 21 (28%) responded to EOM stretch. In all, 40 units with EOM responses were examined and 25 of the 27 tested (93%) also had visual responses. Of the 40 units, 32 could be allocated to layers, thus; layer A, 8 (25%); layer A1, 20 (63%); layer B, 3 (9%); central interlaminar nucleus, 1 (3%). It is interesting that most of the EOM responses were found in layer A1 which recieves the excitatory visual input from the eye whose EOM were stretched. Muscle responsive units occurred with ON- and OFF-centre visual responses of sustained and transient types. PGN. In PGN, 21 units gave EOM responses and most of them were also excited by visual input. The conclusion is that the LGNd and PGN receive an extraretinal proprioceptive signal which should be present during at least large saccadic eye movements. The anatomical pathways which may be involved and the significance of the signal are discussed briefly. PMID- 6245901 TI - Influence of neck afferents on vestibulospinal neurons. PMID- 6245902 TI - Motor cortical modulation of feline red nucleus output: cortico-rubral and cerebellar-mediated responses. PMID- 6245903 TI - Peripheral input pathways to the monkey motor cortex. AB - We have shown (Asanuma et al., 1979c) that the monkey motor cortex receives peripheral somesthetic inputs directly from the thalamus. In the present experiments, we studied the pathways which mediated these inputs by stimulating superficial radial (SR) and deep radial (DR) nerves and recording evoked potentials from the motor and sensory cortices and the following results were obtained: 1. The focus for SR and DR evoked potentials in the sensory cortex was located in a circumscribed small area whereas in the motor cortex, the evoked potentials were distributed in a wide area along the central sulcus including the distal forelimb area. 2. Ablation of the sensory cortex reduced the size, but neither abolished nor changed the latency of the evoked potentials in the motor cortex. 3. Section of dorsal column nearly abolished the evoked potentials in the motor cortex, but only halved their size in the sensory cortex. 4. Section of ventrolateral cervical column including the spinothalamic tract halved the size of evoked potentials in the sensory cortex, but did not change the size in the motor cortex. 5. It is concluded that direct peripheral inputs to the motor cortex are mediated primarily through the dorsal column system whereas the peripheral inputs to the sensory cortex are mediated through both dorsal column and spinothalamic tract. PMID- 6245905 TI - Entamoeba histolytica and Entamoeba invadens: effects of temperature and oxygen tension on growth and survival. PMID- 6245904 TI - Effect on memory processes of anti-vasopressin serum microinjected into the dorsal raphe nucleus: the role of catecholaminergic neurotransmission. AB - Anti-arginine8-vasopressin serum was microinjected into the mesencephalic dorsal raphe nucleus immediately after the learning trial, in a one-trial learning passive avoidance reaction. The treatment attenuated passive avoidance behavior 24 h after treatment, suggesting a role of the endogenous vasopressin of this area in memory processes. On the other hand, the antiserum did not influence passive avoidance behavior if 6-hydroxydopamine was microinjected into the raphe region. The data suggest that the antiserum may have primarily interacted with catecholaminergic terminals, which enter the dorsal raphe nucleus. PMID- 6245906 TI - Schistosoma mansoni: phenol oxidase's role in eggshell formation. PMID- 6245907 TI - Inhibition of nitrosamine formation by ascorbic acid: participation of free radicals in its anaerobic reaction with nitrite. AB - The participation of semiquinone free radicals during the reaction of ascorbic acid with acidified sodium nitrite has been demonstrated by ESR spectroscopy unambiguously for the first time. Scavenging of the nitrosating agent, reflected by the observed free radical concentration, unexpectedly occurs with scarcely varying efficiency over the pH range 0.1--4.5. PMID- 6245908 TI - Quantitation of proinsulin mRNA sequences in hamster insulinoma cells in culture by molecular hybridization. AB - The content of proinsulin mRNA sequences was measured in a cultured cell line established from a transplantable hamster islet cell tumor, by hybridization with proinsulin cDNA. The cells cultured in vitro were found to contain a significant amount of proinsulin mRNA sequences, compared with non-insulin-producing hamster tissues, and seem to be a useful system for the study of insulin gene expression. PMID- 6245909 TI - Some factors affecting Malpighian tubule fluid secretion and transepithelial potential in Locusta migratoria L. AB - Both fluid secretion and transepithelial potential were stimulated by cAMP. Fluid secretion was unaffected by 5-HT over the concentration range 10(-8)-10(-4) M. The presence of ouabain in the bathing medium effected a decrease in transepithelial potential. PMID- 6245910 TI - Renal effects of 8-substituted derivatives of adenosine 3',5'-cyclic monophosphate in dogs. AB - The renal effects of nine, 8-substituted derivatives of 3',5'-cyclic monophosphate were studied in anesthetized mongrel dogs. Infusion of the compounds into a renal artery resulted in an increase of renal blood flow without any effect on blood pressure. Diuretic and natriuretic effects are evident with 6 of the 9 derivatives. As these 8-substituted analogues exert renal effects in a manner similar to that seen with the parent nucleotide, cyclic adenosine 3',5' monophosphate, they may serve as useful pharmacological agents in vivo. PMID- 6245911 TI - Changes in adenylate cyclase and 5-nucleotidase activities in liver membranes from alloxan diabetic rats. AB - Liver membrane adenylate cyclase activity was significantly higher and 5' nucleotidase activity significantly lower in alloxan diabetic rats compared with normal rats. PMID- 6245912 TI - A Ca2+-sensitive myosin light chain kinase, regulating pig carotid smooth muscle actomyosin ATPase. AB - In this paper the correlation between phosphate incorporation into the regulatory light chain of myosin by a Ca2+-dependent myosin light chain kinase, and the Ca2+ sensitive ATPase activity and superprecipitation behaviour of arterial actomyosin, is described. PMID- 6245913 TI - Chromosome fragility and susceptibility of Bloom's syndrome fibroblasts to SV40 transformation. AB - A comparison of the frequencies of chromosomal aberrations and the rates of SV40 transformation was made using fibroblasts obtained from 2 patients with Bloom's syndrome (BS) and from a normal individual. BS cells were found to be more susceptible to chromosome damage, in confirmation of earlier reports, but surprisingly, BS cells were distinctly less prone to transformation. PMID- 6245914 TI - Antiviral activity of glycyrrhizic acid. AB - Glycyrrhizic acid inhibits the growth of several DNA and RNA viruses in cell cultures and inactivates Herpes simplex 1 virus irreversibly. PMID- 6245915 TI - Destruction of virus infected cells by neutrophils and complement. AB - The paper describes an antibody independent mechanism of cytotoxicity whereby virus infected but not uninfected cells are destroyed by the combined presence of neutrophils and complement. PMID- 6245916 TI - Influence of pinealectomy on corticotropin (ACTH). AB - Sensory deprivation produced by removing the eyes and olfactory bulbs in male rats allowed pinealectomy to markedly augment the post-adrenalectomy elevation of ACTH levels. Pineal removal or sensory deprivation separately did not have this effect. Thus, intact sensory input and an intact pineal gland are independently capable of restricting the post-adrenalectomy rise in ACTH levels. PMID- 6245917 TI - Circadian variation of adrenocortical cyclic nucleotides (cyclic AMP and cyclic GMP) in hypophysectomized rats. AB - The existence of a circadian variation in the adrenocortical concentrations of cyclic AMP and cyclic GMP in male adult Wistar rats examined 10 days after hypophysectomy is demonstrated. The results suggest that the circadian variations of adrenocortical cyclic nucleotides observed previously in intact rats might not entirely depend upon pituitary corticotrophin. PMID- 6245918 TI - [Synthesis of alkaline salts of p-tolylthiosulfo acid]. PMID- 6245919 TI - DNase I sensitive chromatin is enriched in the acetylated species of histone H4. PMID- 6245920 TI - Phosphorylation--dephosphorylation of rat liver 3-hydroxy 3-methylglutaryl coenzyme A reductase associated with changes in activity. PMID- 6245921 TI - In vitro ADP-ribosylation of histones by purified calf thymus polyadenosine diphosphate ribose polymerase. PMID- 6245922 TI - Adaptation to salt of the photosynthetic apparatus in Cyanobacteria. PMID- 6245923 TI - Direct measurement of the redox potential of the primary and secondary quinone electron acceptors in Rhodopseudomonas sphaeroides (wild-type) by EPR spectrometry. PMID- 6245924 TI - Adenosine 3':5'-monophosphate phosphodiesterase in chicken erythrocytes. PMID- 6245925 TI - Actin pools in extracts of teratocarcinoma cells, assayed by inhibition of DNase I. PMID- 6245926 TI - Voltage sensitivity of the proton-translocating adenosine 5'-triphosphatase in Streptococcus lactis. PMID- 6245927 TI - Selective inhibition of translation in transformed cells. PMID- 6245928 TI - The hormonal control of glycogen metabolism: dephosphorylation of protein phosphatase inhibitor-1 in vivo in response to insulin. PMID- 6245929 TI - A phosphatase acting on dolichyl phosphate in membranes from neuronal perikarya. PMID- 6245930 TI - Mossbauer spectra of metapyrocatechase. PMID- 6245931 TI - Arachidonate release from rat liver mitochondria in endotoxin shock. PMID- 6245932 TI - Identification and assay of synchrotron radiation-induced alterations on metalloenzymes and proteins. PMID- 6245934 TI - Spectral analysis of the low level chemiluminescence of H2O2-supplemented ferricytochrome c. PMID- 6245933 TI - Active and inactive forms of branched-chain 2-oxoacid dehydrogenase complex in rat heart and skeletal muscle. PMID- 6245935 TI - The role of monoamines in female puberty. AB - The estradiol positive feedback mechanism appears to become mature between days 10 and 20 after birth. Rising serum prolactin levels between day 20 after birth and puberty are correlated with high hypothalamic norepinephrine turnover. High prolactin levels stimulate hypothalamic dopamine (DA) turnover, which may actively inhibit hypothalamic luteinizing hormone-releasing hormone (LHRH) release. Hypothalamic DNA receptor sensitivity is high in 10- to 20-day-old rats and gradually decreases between day 20 after birth and puberty. The reason for this desensitization may be the high hypothalamic DA turnover. This may result in a less strong inhibition of LHRH release allowing the positive feedback action of estradiol to elicit the first preovulatory luteinizing hormone (LH) surge initiating puberty. PMID- 6245936 TI - The mechanisms and regulation of mitochondrial Ca2+ transport. PMID- 6245938 TI - [Hormonally active ovarian tumors]. PMID- 6245937 TI - The Neurospora plasma membrane Ca2+ pump. AB - Plasma membrane vesicles isolated from the eukaryotic microorganism Neurospora crassa by the concanavalin A method catalyze Mg2+-ATP dependent 45Ca2+ accumulation. Since the ATP-responsive vesicles are functionally inverted, the Ca2+ transport system presumably operates as a Ca2+ exit pump in the intact cell. The mechanism of the Ca2+ pump system involves two components: 1) an electrogenic, proton-translocating ATPase (EC 3.6.1.3), which utilizes the chemical energy of ATP hydrolysis to generate a transmembrane electrical potential and pH gradient, and 2) a Ca2+/H+ antiporter, which utilizes the transmembrane pH gradient to energize the active transport of Ca2+. Evidence for this mechanism is presented and the possible implications of these findings for the mechanisms of Ca2+ pumps in other cells are discussed. PMID- 6245939 TI - Characterization of hyperandrogenism with insulin-resistant diabetes type A. AB - The characterization of the hyperandrogenism of two sisters with type A insulin resistant diabetes and hirsutism is presented. Testosterone (T) and androstenedione levels were elevated in peripheral serum. These were not markedly affected by infusion of adrenocorticotropic hormone. In patient 1 glucocorticoid suppression decreased T levels by 50% and androstenedione levels by 30% but had no effect on them in patient 2. Estrogen-progestin suppression markedly reduced testosterone levels in both patients. The blood production of T in patient 1 was 0.8 mg/day and in patient 2 was 4.5 mg/day, both of which are elevated. Selective venous catheterization in patient 2 revealed markedly elevated testosterone levels in the ovarian veins, and polycystic ovaries were found at subsequent laparotomy. These endocrine studies have shown that the source of excessive testosterone in these patients is excessive production by the ovaries, and it can be suppressed by oral contraceptives. PMID- 6245940 TI - Studies on nonoxynol-9. III. Effect on fibroblasts and spermatozoa. AB - Seven nonionic detergents of the Igepal CO series differing in molecular size and including nonoxynol-9 and a representative anionic (SDS) and cationic (Cepacol) detergent were tested as to their relative cytotoxicity. The biologic effects of these detergents on human W1--38 fibroblasts (DNA and glycosaminoglycans synthesis) and on the motility of human spermatozoa were studied. The relative order of cytotoxicities for both fibroblasts and spermatozoa was cationic greater than nonionic greater than anionic. The concentration of nonoxynol-9-inhibiting fibroblast activity was approximately 30 times less than the amount needed to immobilize spermatozoa. It is concluded that CO-630, used as a source of nonoxynol-9, is the most effective polymer to inhibit spermatozoa and also fibroblasts. PMID- 6245941 TI - [The effects of ACTH, insulin hypoglycemia, dexamethasone and metyrapone on corticosterone secretion in healthy subjects: a comparison with cortisol secretion (author's transl)]. PMID- 6245942 TI - [Studies on angiotensin II receptors in the adrenal glands and in the aorta (author's transl)]. AB - The angiotensin II receptor in the rabbit, rat and human adrenal gland and that in the rabbit and rat aorta were studied by using [3H]-angiotensin II ([3H]-AII). The adrenal glands and the aorta of each species were centrifuged at 20,000Xg for 30 min, and pellets which contained 95% of binding sites were collected and diluted by a buffer [20 mM Tris-HCl buffer (pH 7.4), 120 mM NaCl, 0.2% BSA, 1 mM EDTA] and used as a membrane fraction. The binding study was done by incubating the membrane fraction and [3H]-AII. After incubation at 25 degrees C for 30 min, the binding of the membrane fraction and [3H]-AII reached the equilibrium state, and free and bound angiotensin II were separated by 0.48 micrometer filters. Protein concentration was determined according to the method of Lowry. The binding sites fulfilled the criteria of the receptor which has organ and structure specificities, high affinity and reversibility. We could thus measure angiotensin II receptor in this study correctly and concisely. The properties of the angiotensin II receptor were analysed by Scatchard plot. The number of rabbit adrenal receptors (12833 +/- 2115 x 10(-15) mol/mg.protein) (M ++/- SD) was greater than that of the rat (1780 +/- 166 x 10(-15) mol/mg.protein) and that of the human (356 +/- 124 x 10(-15) mol/mg.protein). But the dissociation constant of all species was the same. The number of aorta binding sites was less than that of the adrenal in rabbits and rats. But the dissociation constant of rabbits and rats aorta binding sites was quite similar to that of adrenal glands. PMID- 6245943 TI - [Comparison of blood pressure responses to captopril, an orally active converting enzyme inhibitor, in rats with various forms of experimental hypertension (author's transl)]. PMID- 6245944 TI - [An assay of ACTH using isolated adrenal cells and studies for the determination of plasma ACTH concentrations (author's transl)]. PMID- 6245945 TI - [The long term effect of the oral converting enzyme inhibitor captopril in hypertensive patients (author's transl)]. PMID- 6245946 TI - Immunoresponsiveness of herpesvirus SA 8 infected infant baboons. PMID- 6245947 TI - [Dietary fiber and diabetes mellitus]. PMID- 6245948 TI - Cell kinetic study of human cancers transplanted to nude mice. AB - Using 3H-TdR pulse labelling, the cell kinetics of four, serially transplantable, human tumors were studied in athymic nude mice. Squamous cell carcinoma of the lung, tongue and esophagus showed relatively similar cell kinetic parameters. The growth of an oat-cell carcinoma was initially very slow in mice and its growth fraction was unexpectedly small with a relatively low labelling index. Its postmitotic phase was very short. It was concluded that the nude mice/human tumor system may be useful for cell kinetic studies of human tumors from the standpoint of tumor biology and therapy. PMID- 6245949 TI - Purified cytochrome P-450: spin-state control of the haemoprotein redox potential [proceedings]. PMID- 6245950 TI - The binding of rabbit bone inhibitor of collagenase to concanavalin A--Sepharose [proceedings]. PMID- 6245951 TI - A simple assay for the polyphosphoinositide phosphodiesterase of the human erythrocyte membrane [proceedings]. PMID- 6245952 TI - Interactions of gangliosides with adenylate cyclase and cyclic AMP phosphodiesterase in rat brain homogenates and synaptosomes [proceedings]. PMID- 6245954 TI - Computer simulations of the rate of change of concentration of adenosine 3':5' cyclic monophosphate after stimulation of adenylate cyclase activity [proceedings]. PMID- 6245953 TI - The effect of membrane-fluidizing agents on sodium-pump activity in erythrocytes [proceedings]. PMID- 6245955 TI - The effects of adenine derivatives on urate biosynthesis by isolated chicken liver cells [proceedings]. PMID- 6245956 TI - Adenosine-binding to cerebral preparations in interpretation of adenosine activation of adenosine 3':5'-cyclic monophosphate formation [proceedings]. PMID- 6245957 TI - Analysis of the effects of adrenaline and glucagon on calcium ion movement in liver cells by using a simple compartmental model [proceedings]. PMID- 6245958 TI - The control of phosphatidylinositol turnover in cell membranes. PMID- 6245959 TI - Use of phospholipid-converting enzymes for the study of membrane-bound enzymes. PMID- 6245960 TI - Enzymes linked to phosphatidylinositol in plasma membranes. PMID- 6245961 TI - Studies of the sodium-plus-potassium-dependent adenosine triphosphatase by removal and replacement of lipid. PMID- 6245962 TI - On the mechanism of activation of the MgATP2--dependent phosphorylase phosphatase isolated from dog liver [proceedings]. PMID- 6245963 TI - Comparative studies on ligand binding to cytochrome c oxidase and other haem proteins [proceedings]. PMID- 6245965 TI - Restriction endonuclease EcoR1 binds non-specifically to deoxyribonucleic acid [proceedings]. PMID- 6245964 TI - Inhibition of elastase and fibrinolysin by reducing and oxidizing agents [proceedings]. PMID- 6245966 TI - The metabolism of ranitidine in animals and man [proceedings]. PMID- 6245967 TI - Changes in developmental-specific enzyme activities during experimental hepatocarcinogenesis in the rat in vivo [proceedings]. PMID- 6245968 TI - Studies on the hepatotoxicity and metabolism of coumarin in the rat [proceedings]. PMID- 6245969 TI - The use of restriction-enzyme fragments of cloned deoxyribonucleic acid for human globin-gene mapping [proceedings]. PMID- 6245970 TI - Physical mapping of part of the tumorigenic deoxyribonucleic acid (T-DAN) region of the tumour-inducing (Ti) plasmid from Agrobacterium tumefaciens strain C58 [proceedings]. PMID- 6245971 TI - Characterization of poly(adenosine diphosphate ribosylated) protein isolated from mouse L1210 cells in vivo [proceedings]. PMID- 6245972 TI - The effect of phenones on poly(adenosine diphosphate ribose) synthetase from porcine thymus [proceedings]. PMID- 6245973 TI - Production of human immunoglobulin anti-D (Rh0) for intravenous administration, for a national Rh prophylaxis programme [proceedings]. PMID- 6245974 TI - [3H]Spiroperidol binding in bovine caudate nucleus [proceedings]. PMID- 6245975 TI - A comparison of the inhibitory effects of cromoglycate on cyclic nucleotide phosphodiesterase activity in intact lymphocytes, macrophages and mast cells [proceedings]. PMID- 6245976 TI - Comparative efficacy of 3-day and 7-day chemotherapy with pivmecillinam in urinary tract infections in general practice. PMID- 6245977 TI - An open evaluation of a 3-day course of pivmecillinam (ten 200 mg tablets) in women with acute uncomplicated cystitis. AB - One hundred and eighty-four women, with acute uncomplicated cystitis, received a 3-day course of pivmecillinam comprising an initial 400 mg (two tablets) dose, followed by 200 mg every 8 hours; a total of ten tablets. A satisfactory clinical response was achieved in 91% of patients. Bacteriological success was observed in 94% of sixty-eight patients with a proven infection. Side-effects were reported in sixteen patients (8.4%). Two patients ceased therapy prematurely. Pivmecillinam did not select out resistant Gram-negative organisms. A trend towards reinfection with Gram-positive cocci was observed. The possible significance of reinfection with different organisms is discussed. PMID- 6245978 TI - Prolactin and tadpole metamorphosis. Evidence of prolactin receptors in premetamorphic Rana catesbeiana liver and tail fin. AB - The binding characteristics of ovine prolactin (OPRL) to a particulate fraction from liver and tail fin of Rana catesbeiana tadpoles were studied. The specific binding of [125I]oPRL to both tissues was found to be a saturable process with a single class of binding sites in each tissue. Although the dissociation constants were similar for each tissue, the tail fin demonstrated a 10-fold higher binding capacity than the liver tissue. Pretreatment of the liver and tail fin particulate fractions with degradative enzymes revealed that trypsin and phospholipase C reduced the subsequent specific [125I]oPRL binding in both tissues. However, neuraminidase treatment decreased the prolactin binding in the liver while having no effect on the tail fin. The binding of prolactin to the amphibian tissues was found to be specific for prolactin and growth hormones. [125I]oPRL binding to both tissues was a reversible process although the dissociation rate was faster for the tail fin than for the liver. Therefore, prolactin receptors are associated with both a prolactin responsive tissue, the tail, and an unresponsive tissue, the liver, in the tadpole. PMID- 6245979 TI - Relation of membrane property of microsomes to androgen biosynthesis. AB - Spin-labelled fatty acids I(12,3) and I(1,14) were incorporated into microsomal membrane of cryptorchid mouse testis and Leydig cell tumor as well as liver. The freedom of motion of spin of I(12,3) was more restricted in testis microsome than in liver. At the lower temperatures, the freedom of motion of spin in the tumor microsomes was similar to that in the testis, but at higher temperature (20-50 degrees C) was much greater. Plotting of the empirical parameter, h0/h-1, calculated by the spectra of I(1,14), against the reciprocal of the absolute temperature clearly showed two inflection points in both liver and testis microsomes, one at 19 decrees C and the other at 30 degrees C. On the other hand, tumor microsomes lacked these break points and permitted spin to move more freely. These results suggest that tumor microsomes contain the increased fluidity. The importance of membrane fluidity in relation to steroid biosynthesis was also discussed. PMID- 6245980 TI - Responses of Y1 adrenocortical tumor cells to o-nitrophenyl sulfenyl ACTH. AB - NPS(o-nitrophenyl sulfenyl)-ACTH stimulated steroidogenesis in Y1 cells to the same maximum level as did ACTH, but with a 60-fold lower potency than the native hormone. NPS-ACTH also stimulated the extracellular accumulation of cAMP in Y1 cells with lower potency than the unmodified hormone. The amount of cAMP accumulated in the presence of NPS-ACTH approached 75% of the maximum with ACTH. In Y1 plasma membranes, NPS-ACTH was a partial agonist of adenylate cyclase activity, witn an efficacy dependent upon the type of guanyl nucleotide present. The steroidogenic responses of two Y1(Kin) mutants and two Y1(Cyc) mutants to NPS ACTH paralleled their responses to ACTH and reflected closely their defects in cAMP-dependent protein kinase and ACTH-sensitive adenylate cyclase activity. These data imply an obligatory role for adenylate cyclase and cAMP-dependent protein kinase activities in stimulation of steroidogenesis in Y1 cells by NPA ACTH. PMID- 6245981 TI - The effects of cell density and starvation on early developmental events in Dictyostelium discoideum. PMID- 6245982 TI - Contribution of cholinesterase to developmental decreases in the time course of synaptic potentials at an amphibian neuromuscular junction. PMID- 6245983 TI - Use of a common standard for comparison of insulin C-peptide measurements by different laboratories. AB - A synthetic human C-peptide analogue has been used as a common standard for the comparison of insulin C-peptide measurements in seven assay systems in six laboratories. Even in terms of this common standard there was statistically significant numerical heterogeneity between laboratories for estimates of the C peptide content of the same plasma samples. However, the consistency in ranking order of estimates of C-peptide in the plasma samples between laboratories suggests that laboratories are in most cases measuring at least similar immunoreactive constituents and that a reference plasma might prove useful in comparing results between laboratories. Until a more suitable reference material is available, the synthetic analogue, 64 formyllysine C-peptide, in ampoules coded 76/561, will be made available for research purposes. PMID- 6245984 TI - Testosterone effect on experimental diabetes mellitus in encephalomyocarditis (EMC) virus infected mice. AB - A diabetes mellitus-like disease occurs in male DBA/2 mice infected with the M variant of the encephalomyocarditis virus. Female mice of this strain sustain systemic infection, but rarely exhibit hyperglycaemia. The diabetogenic effects of the virus were studied in 3 groups of adult DBA/2 males-castrates, castrates treated with testosterone, and sham-operated controls. After infection, pancreatic insulin concentrations decreased precipitously to approximately 10% of control values in intact males and castrates treated with testosterone; hyperglycaemia occurred concomitantly in both groups. In contrast, untreated castrates failed to develop hyperglycaemia and the effect on the insulin content of the pancreas was less striking. PMID- 6245985 TI - Liver collagenase in murine schistosomiasis. AB - Mice infected with Schistosoma mansoni represent a model for study of the most prevalent form of hepatic fibrosis in humans. In the present study, collagenase activity was measured in relation to collagen synthesis and accumulation in the livers of mice 6-11 wk after after infection. Total and latent collagenase and elastase activities and collagen synthesis were maximal 8 wk after infection and decreased thereafter, whereas collagen content progressively increased to the 11th wk. Maximal enzymatic activity coincided with the known peak of host cellular immune responses. Collagenase and elastase activities were isolated from liver homogenates. Isolated schistosome eggs did not contain collagenase or elastase activities. Collagenolytic activity had the characteristics of a tissue collagenase. These data show that marked increases in collagenase activity occur together with increased collagen synthesis in this animal model. Continued accumulation of liver collagen under these conditions suggests an imbalance between increased collagen synthesis and degradation. PMID- 6245986 TI - Copper and the liver. PMID- 6245987 TI - Follicle-stimulating hormone (FSH) receptors in the testis of the newt, Cynops pyrrhogaster, and comparison of temperature dependency of the receptors with those of the other vertebrates. PMID- 6245988 TI - Alterations in type I and type II protein kinases in the thyroid and adenohypophysis in response to a dietary goitrogen. PMID- 6245990 TI - [Methods for biological research on the fibrogenicity of coal dust]. PMID- 6245989 TI - Fine structural effects of hypophysectomy on the aging rat pineal gland. AB - A study was undertaken to examine the effects of pituitary removal on age-related changes in the female rat pineal. Three 9-month-old controls, three 23-month-old controls and three rats hypophysectomized at 19 months and sacrificed at 23 months of age were utilized. Electron microscopic evaluation indicated that following hypophysectomy there was a significant loss of lipid droplets, no change in the frequency of light and dark pinealocytes or cytoplasmic dense bodies (probably lipofuscin), a trend towards increased granular deposits between cells, no change in the number of pinealocytes with nuclear invaginations and decreased numbers of cells with nuclear inclusions. The results indicate that while some tissues (kidney) may show reduced aging indices following hypophysectomy other tissues such as the pineal may be detrimentally affected. PMID- 6245991 TI - [Treatment of oat cell cancer of the lung]. PMID- 6245992 TI - Radioactive lymphography (endolymphatic radiotherapy) in Hodgkin's disease. Statistical study of 373 cases. PMID- 6245993 TI - [The colon in laxative abuse]. PMID- 6245994 TI - [Diseases of the exocrine pancreas in infants and children. A review. 3. Pseudocysts, cysts, tumors: functional disorders of the exocrine pancreas secretion; pseudo-pancreatic insufficiency]. AB - The aim of the present work is to provide a new classification of the exocrine pancreatic diseases in childhood by means of a simple and practicable scheme which is in line with the recognized classification of Internal Medicine. The article presents a definite distinction between organic diseases of the pancreas - such as deformities, congenital insufficiences, pancreatitis, cysts and tumors - functional disturbances of the pancreas secretion and pseudo-pancreas insufficiency caused by extrapancreatic factors. New investigative methods help to distinguish between various disorders encountered. PMID- 6245995 TI - Elevated insulin/glucagon ratios and decreased cyclic AMP levels accompany the glycogen and triglyceride storage syndrome in the hypothyroid chick. AB - The role of endogenous glucagon and insulin on the hepatic glycogen and triglyceride storage syndrome in propylthiouracil (PTU)-induced hypothyroidism was investigated in the chick. PTU feeding in the diet resulted in a progressive increase in liver glycogen concentration associated with a concomitant decrease in hepatic glucose-6-phosphatase (G-6-Pase) activity. Plasma glucagon level was significantly decreased and insulin significantly increased after two days of PTU administration. These enzyme and hormone changes were associated with a significant increase in hepatic glucose-6-phosphate (G-6-P) and a decrease in cyclic AMP levels. Although our results do not directly prove, the data does suggest that the hepatic glycogen storage syndrome observed in the PTU-induced hypothyroidism in the chick is mediated through changes in pancreatic glucagon and insulin secretion. The extent of glycogen accumulation was inversely related to G-6-Pase which is a rate limiting glycogenolytic enzyme. A significant increase in the plasma insulin/glucagon ratio, along with a significant decrease in the hepatic cyclic AMP concentration, could most likely also account for the excessive hepatic triglyceride accumulation in the PTU-treated chicks. PMID- 6245996 TI - Normal somatomedin and somatomedin receptors in achondroplastic dwarfism. AB - It has been proposed that the basic abnormality in achondroplasia may be a quantitative defect in endochondral new bone formation secondary to decreased synthesis of somatomedin (SM) or abnormal binding of SM to specific receptors. To test this hypothesis, we have measured plasma SM levels and SM receptors on circulating mononuclear cells obtained from 5 achondroplastic dwarfs and 5 age matched controls. Plasma SM levels were 0.82 +/- 0.14 U/ml (mean +/- S.E.M.) for the achondroplastic dwarfs and 0.90 +/- 0.12 U/ml for the controls. The specific binding of 125I-SM to 50 x 10(6) mononuclear cells was 7.66 +/- 1.11% for the dwarf group and 7.66 +/- 1.16% for the controls. Achondroplastic and control cells possessed equal numbers of receptor sites and identical receptor affinity for SM. The data indicate that plasma SM levels and SM binding to circulating mononuclear cells are normal in achondroplastic dwarfs and suggest a primary intrace-lular defect. PMID- 6245997 TI - Changes in plasma cyclic nucleotides levels during various acute physical stresses. AB - Studies were performed with healthy volunteers to determine the effects of various stresses known to increase sympathetic nerve activity on the plasma concentration of cyclic AMP and cyclic GMP. Plasma cyclic AMP rose promptly in response to exercise; the elevation was completely abolished by a simultaneous injection of propranolol. Plasma cyclic GMP rose slightly after exercise; the elevation was completely abolished by a simultaneous injection of atropine. No significant changes occurred during tilting and cold pressor stress. The increase in plasma concentrations of cyclic AMP and cyclic GMP may serve as putative indices for beta-adrenergic, and cholinergic functions respectively during exercise of humans. PMID- 6245998 TI - Artifacts in the radioimmunoassay of ACTH in tissue extracts and plasma. AB - Artifacts in studies employing the radioimmunoassay of ACTH may be introduced by the presence of high concentrations of protein or other substances which interfere in the antigen-antibody reaction and by unsuspected damage to the labeled ACTH. We have confirmed the reports of others that extracts of pancreatic, gastrointestinal and other nonpituitary tissues do decrease the binding of labeled ACTH to specific antibody. However, since all known forms of ACTH bind to and can be quantitatively eluted from QUSO, and the apparent immunoreactivity in these tissues does not, we conclude that there is no authentic ACTH detectable in the gut. PMID- 6246000 TI - A possible method of achieving better medication compliance. PMID- 6245999 TI - Release of cyclic AMP from chicken erythrocytes. AB - Exposure of chicken erythrocytes to epinephrine results in the appearance of considerable amounts of the nucleotide in the incubation medium. The release of cAMP from the cells to the surrounding medium is dependent upon its overproduction by adenyl cyclase. However, the efflux of cAMP was found not to be directly related to the total intracellular level of the nucleotide. The rate of cAMP release also remains unchanged under conditions of inhibited intracellular degradation of the nucleotide. The data presented suggest that cAMP release is not likely to serve as a regulatory mechanism which participates in the control of intracellular level of the nucleotide. The transport of cAMP from the cells to the surrounding medium was found to be reduced by the presence of NaF, iodoacetate and caffeine. PMID- 6246001 TI - Patterns of cyclic AMP phosphodiesterases during rat testis development. AB - Cyclic AMP phosphodiesterase (PDE; E.C.: 3.1.4.17) plays a crucial role in the regulation of intracellular cAMP levels arising from the hormonal activation of membrane-bound adenylcyclase in the target cell. In the present study, we revealed a complex sequence of appearance and disappearance of individual molecular electrophoretic forms of PDE during the development of the rat testis. Kinetic analysis of cAMP hydrolysis in crude testis homogenates of developmental stages where multiple PDE isozymes are expressed revealed complex kinetic behavior of PDE. After separation of individual isozymes by elution from starch gel blocks, several enzymatic forms still act with complex kinetics, indicating negatively cooperative behavior. The stage specificity of the kinetic properties of PDE appears to be related to the hormonally regulated events leading to the initiation of male puberty. PMID- 6246002 TI - Formal genetics of phosphoglycolate phosphatase (PGP): investigation on 272 mother-child pairs. AB - PGP (phosphoglycolate phosphatase, E.C. 3.1.3.18) phenotypes were determined by starch gel electrophoresis in 272 mother-child pairs from S. W. Germany. The results confirm and formal hypothesis of three alleles, PGP1, PGP2 and PGP3 at an autosomal locus PGP. PMID- 6246004 TI - [Herpesvirus infection]. PMID- 6246003 TI - Ischemic cardiovascular complications concurrent with administration of captopril. A clinical note. AB - Administration of potent vasodepressor agents such as the angiotensin converting enzyme inhibitor, captopril, may precipitate myocardial ischemic events in patients with coronary artery disease, particularly if this treatment is preceded by a discontinuation of beta-blocking drugs such as propranolol. In one case studied, a patient experienced three episodes of angina pectoris under these conditions; in another, acute anterior myocardial infarction was suspect. PMID- 6246005 TI - Pivmecillinam in the treatment of therapy resistant urinary tract infections. A comparison with pivmecillinam, pivampicillin and their combination. AB - Pivmecillinam is a new penicillin-like compound belonging to the so-called amidinopenicillins and characterized by a high antibacterial activity against Enterobacteriaceae and by demonstrated synergism when combined with other beta lactam antibiotics. In this prospective trial geriatric patients with a stationary indwelling catheter and significant bacteriuria caused by Enterobacteriaceae were treated for four weeks with pivmecillinam, pivampicillin or various combinations of the two compounds. Urine specimens were obtained weekly, and in eight patients receiving pivmecillinam 75% of the urine samples were free from Enterobacteriaceae during the period of treatment. The figure was 91% in 24 patients receiving combination therapy. In seven patients treated with an equimolar dose of pivampicillin alone 43% and 23% of the urine specimens, controlled during the first and the second havles of the treatment period respectively, Enterbacteriaceae was eradicated. In this group there was a marked and increasing tendency towards infections caused by more resistant strains of Enterobacteriaceae as the treatment progressed. The latter is keeping with the observation that pivmecillinam, as opposed to ampicillin, apparently does not cause any selection of resistant Enterobacteriaceae in the faecal flora which is the main source of urinary pathogens. PMID- 6246006 TI - Mecillinam and ampicillin separately or combined in gram-negative septicemia. AB - Of 20 patients with gram-negative septicemia treated with mecillinam alone or in combination with ampicillin, successful therapeutic results were obtained in 16. In 11 patients treated with ampicillin alone, three failures responded successfully to a combination of mecillinam and ampicillin. Mecillinam MIC values of isolated Enterobacteriaceae were 0.05-0.4 micrograms/ml. In patients receiving 5 mg/kg mecillinam intravenously every six hours, the mean 0.5 hour concentration was 11.0 micrograms/ml and in those given 10 mg/kg 23.3 migcrograms/ml. No serious side effects were recorded. One patient on mecillinam developed an exanthema, as did three patients on combined therapy. PMID- 6246007 TI - Differential inhibition of Epstein-Barr virus induction by the amino acid analogue, L-canavanine. AB - The effect of an amino acid analogue, L-canavanine, on the synthesis of Epstein Barr virus (EBV) antigens was investigated in lymphoblastoid cells. The analysis revealed that after infection of BJAB and NC-37 cells with P3HR-I EBV synthesis of early antigen (EA) was not affected by canavanine in concentrations up to 8.4 mM. The synthesis of EBV-determined nuclear antigen (EBNA) and of viral capsid antigen (VCA) was significantly inhibited at concentrations higher than 2.8 mM. Spontaneous induction of EA in P3HR-I cells was not affected by canavanine. On the other hand, EA induction by the tumor promoter TPA resulted in some viral antigen induction depending on the time period of TPA exposure. Pretreatment of the cells overnight with canavanine followed by washing and addition of the tumor promoter did not suppress EA induction by TPA. These data support the concept that EA induction by superinfection follows a different pathway from antigen induction by chemical inducers. PMID- 6246008 TI - Effector and enhancing lymphoid cells in plasmacytoma-bearing mice. II. Dynamic changes during tumor progression. AB - The Winn assay was used for the study of effector (tumor-inhibiting) and enhancing (tumor-promoting) lymphoid cells in BALB/c mice bearing MOPC-104E plasmacytomas. Kinetic studies with thymus, lymphnode, spleen and bone-marrow cells revealed that spleen, lymph node and to a lesser extent bone-marrow cells from 7- and 10-day tumor-bearers inhibited MOPC-104E growth, while at day 13 all three cell populations enhanced tumor growth. However, at day 16 strong tumor inhibition was observed again by spleen cells and to a lesser extent by lymph node cells and thymocytes. Peritoneal cells from normal and tumor-bearing (7 and 10 days) animals enhanced tumor growth significantly. Separation of spleen cells on nylon wool columns showed that at 10 days the effector cells were T lymphocytes, but at a later stage (35 days) a different effector mechanism was present in the spleen. Treatment of MOPC-104E recipients with carrageenan or silica had little influence on tumor growth, but marked tumor inhibition occurred after lethal irradiation and bone-marrow reconstitution. This latter observation, together with the finding that bone-marrow, lymph node and peritoneal cells from normal donors enhanced tumor growth in several experiments, suggests that this plasmacytoma, like hormone-dependent tumors, requires lymphocyte-derived growth factors. PMID- 6246009 TI - Spontaneous immune response of bovine leukemia-virus-infected cattle against five different viral proteins. AB - The sera from cattle exposed to bovine leukemia virus (BLV) have been studied by the radioimmunoprecipitation assay (RIPA) of disrupted virus proteins. All sera of animals with the adult form of lymphosarcoma precipitated four different viral proteins: gp51, gp35, p24 and p12. In contrast, the sera of five animals with the juvenile or thymic forms of bovine lymphosarcoma were completely devoid of precipitating activity against BLV proteins, confirming the absence of relationship between these rare malignant diseases and BLV infection. The sera of non-leukemic cattle from areas of high risk of exposure to BLV were either negative or positive to a lower degree than the sera of lymphosarcomatous cows. When positive they precipitated gp51, p24 and p12. Only one serum precipitated gp35. The difference was probably quantitative, the sera of leukemic animals having higher levels of precipitating activity against all the viral proteins. The anti-gp51 reactivity was in most cases the strongest, whatever the origin of the serum. In the rare sera which were positive in the classical anti-gp51 radioimmunoassay (RIA) but negative in the anti-p24 RIA, an anti-p24 activity was, however, detected by the RIPA. These results suggest that BLV-infected cows regularly produce antibodies reacting with four different viral proteins including minor viral components. In three cases with no other special features a low level of activity was detected against a fifth component: p15. There was no apparent correlation, however, between the antibody response and an hypothetical protection against BLV-induced disease. PMID- 6246010 TI - Partial characterization of viral DNA from human genital warts (Condylomata acuminata). AB - By centrifuging total cellular DNA derived from human genital warts (condylomata acuminata) in CsCl-ethidium bromide gradients, supercoiled DNA was isolated. The molecular weight of this DNA was determined by agarose gel electrophoresis and amounted to 5.1 X 10(4). This DNA isolated from an individual genital wart was annealed to fractions of aqueous supernatants of the same wart after prior centrifugation of this material in CsCl density gradients. Annealing was observed at a density of approximately 1.32 g/ml corresponding to the expected density of papilloma virus particles. Since such particles were also observed in the same preparation by electron microscopy, it was concluded that the supercoiled DNA molecules were derived from papilloma virus nucleocapsids. Positive hybridization was found with six additional preparations from individual genital warts. Therefore, it seems that the isolated DNA prevails in condylomata acuminata. The DNA is different from the other five types of human papilloma viruses described thus far in regard to its restriction endonuclease cleavage patterns. The virus analyzed is tentatively designated as human papilloma virus type 6 (HPV 6). PMID- 6246011 TI - Divergent effects of macrophage toxins on growth of primary tumors and lung metastases in mice. AB - The effects of silica and carrageenan on primary tumor growth and metastases were evaluated in c57bl/6 and BALB/c mice transplanted with the poorly immunogenic Lewis lung (3ll) carcinoma, mFS6 sarcoma and Madison 109 carcinoma spontaneously metastasizing to the lungs. Silica and carrageenan significantly enhanced lung metastases and decreased primary tumor weight in all three experimental models. A similar augmentation of lung secondaries was found after i.v. inoculation of 3LL tumor cells. The effects of carrageenan on primary 3LL tumor growth and metastases were observed also in thymus-deprived animals. The effect of macrophage toxins was studied also in C57BL/6 mice transplanted with the M5076/73A ovarian carcinoma. This tumor spontaneously metastasizes to various abdominal organs, but not to the lung. After treatment with carrageenan, lung metastases were observed, but no effect on secondaries at other anatomical sites or on the primary tumor was detectable. It is suggested that host defense mechanisms impaired by silica and carrageenan may have divergent effects in the regulation of growth of some primary tumors and spontaneous lung metastases. PMID- 6246012 TI - Isolation of a series of novel variants of murine mammary tumor viruses with broadened host ranges. AB - We have previously isolated mouse mammary tumor virus (MMTV) host range variants by serial virus passage in feline cells. These variants productively infect cells of a broad range of species but replicate most efficiently in feline cells. We report here the isolation of a series of novel MMTV host range variants that have the ability to replicate with high efficiency in murine, rat, canine and human cells, respectively; these variants were isolated by serial virus passage in cells of each respective species. These new variants, furthermore, all retained their ability to efficiently replicate in feline cells, and each exhibited unique host range properties. The novel MMTV variants obtained from murine, rat, feline, canine, and human cells showed no overt evidence of recombination with endogenous type-C viruses in that they retained their antigenic reactivities in group specific radioimmunoassays for MMTV polypeptides, and were unreactive for type-C virus proteins when tested by radioimmunoassays and DNA polymerase assays. These novel MMTV host range variants now broaden the spectrum of studies that can be undertaken involving MMTV replication and the initiation and promotion of virus mediated mammary cell transformation. PMID- 6246013 TI - Liver and kidney tumors induced by N-nitroso-dimethylamine in Xenopus borealis (Parker). AB - N-nitroso-dimethylanine dissolved in aquarium water at a concentration of 400 ppm (1/4 of the LD50/30d) induced malignant tumors in 39 (54.2%) out of 72 young adult animals of the amphibian species Xenopus borealis. The first tumor was detected at 11 weeks, and the average latency was 35.1 weeks. Tumors were located in the liver (32 cholangiocarcinomas and 13 hepatocellular cancers) and the kidney (9 adenocarcinomas and 2 anaplastic cancers). Thirteen animals bore two or more types of tumors. These results demonstrate that a high percentage of tumors can be induced in amphibians by chemical carcinogens if appropriate methods are used. PMID- 6246014 TI - Methionine enkephalin and isosteric analogues. Part II.: Receptor conformation of methionine enkephalin. AB - Biological activities are reported for two different types of analogues of methionine enkephalin. Cyclic analogues, bridged between the amino- and carboxy- terminals of the parent peptide, are inactive. In contrast, significant levels of activity are displayed by linear isosterically modified analogues in which the Tyr1-Gly2 peptide bond is replaced by either -CH2NH- or -CH2CH2-. Similar replacements of the Gly2-Gly3 peptide bond yield compounds with much reduced potency. These modifications serve as useful probes of the receptor conformation. Based on these findings, a model is proposed for interaction between enkephalin and its receptor. PMID- 6246015 TI - Alternative synthesis of corticotropin-like intermediate lobe peptide (human CLIP). A peptide corresponding to the sequence of human ACTH-(18--39). AB - A novel synthesis of human CLIP, a peptide corresponding to the sequence of human ACTH-(18-39) is described. The dodecapeptide chain was assembled by a combination of fragment condensation and stepwise synthesis while using N alpha benzyloxycarbonyl and side chain tert.-butyl-derived protective groups combination. The final deprotection was performed by acidolysis in trifluoroacetic acid. The end product was purified by ion exchange chromatography on carboxymethyl cellulose. PMID- 6246016 TI - Synthesis and analgesic activity of human beta-endorphin analogs substituted at positions 17, 18, or 19. AB - Three peptide analogs of beta-endorphin which are substituted in positions 17, 18 or 19 have been synthesized and their analgesic potencies have been measured by the tail-flick method in mice. The results showed that the replacement of Phe-18 or Lys-19 by alanine reduced the potency to 15% whereas the replacement of Leu-17 by alanine reduced the analgesic potency to 68%. PMID- 6246017 TI - Free radicals in dicarboxylic acids: an e.s.r. study of gamma-irradiated single crystals of glutaric acid at 77 K. AB - Electron spin resonance techniques were used to study the gamma-radiation-induced free radicals in single crystals of glutaric acid in the temperature range from 77 K to 300 K. Three different radicals are stabilized at 77 K. The decarboxylation radical is the dominant species and the other two radicals are assigned to the anion and to the substituted acetyl sigma-radical. When the temperature of the crystal is raised, these radicals disappear and the previously studied room temperature radicals appear. E.S.R.-data and the results from semi empirical INDO-MO calculations were compared in order to elucidate the structures of the various radicals. PMID- 6246018 TI - Radiation-induced oxidation of 4-hydroxy-2,2,6,6-tetramethylpiperidine to paramagnetic nitroxide free radicals. PMID- 6246019 TI - A method for a simultaneous decrease of strontium, caesium and iodine retention after oral exposure in rats. PMID- 6246020 TI - [Ectopic hormone production in the small-cell bronchial carcinoma. Biological and immunological aspects]. PMID- 6246021 TI - Experimental type 2 herpes simplex ophthalmitis in the newborn rat. AB - An animal model for the study of type 2 herpes simplex virus (HSV2) ophthalmitis is described. Wistar rats were inoculated intracerebrally with HSV2 at 0, 5, 10, 15, 20, or 30 days of age. Eyes and brain from all animals, whether they survived or succumbed with encephalitis, were collected for microscopic and virologic studies. Up to 20% or more of the HSV2-inoculated rats had lesions in the cornea, uveal tract, and/or retina. Herpetic keratiis occurred in a few animals while the eyelids were still fused, indicative of internal spread of HSV2. Intranuclear inclusions were observed in corneal epithelium and neural retina, and herpesvirus particles were demonstrated in the cornea, iris, and retina. Lesions of the cornea and iris were also visualized by scanning electron microscopy. Virus was isolated from over 40% of the eyes tested. In general, titers of the virus in the eyes were less than those in the brains of HSV2-inoculated rats. The newborn rat thus represents another animal model to study herpetic ophthalmitis. Unlike most studies, ocular lesions were produced by a route other than the usual topical or intraocular inoculation of the virus. PMID- 6246022 TI - Influence of calcium on retinal ATPases. AB - The activity of Mg2+-ATPase and Na+-K+-ATPase was measured in media of calcium concentrations ranging from 10(-9)M to 10(-3)M, with retinal homogenates from rat and rabbit. In both species calcium stimulated the Mg2+-ATPase and inhibited Na+ K+-ATPase. In the rat, activity of Na+-K+-ATPase fell by 75% as calcium was increased from 10(-8)M to 10(-7)M and reached 90% inhibition only at 10(-3)M. By contrast, the activity in the rabbit fell gradually to a 90% inhibited state, over the range 10(-8)M to 10(-3)M. Calcium activated the Mg2+-ATPase by a maximum of 50% in each species, at a concentration of 10(-8)M in the rat and over a broader concentration range between 10(-5)M and 10(-4)M in the rabbit. It is postulated that maintenance of intracellular calcium at low levels by the Ca2+ activated Mg2+-ATPase or other cellular mechanisms is essential for the activity of the membrane-bound Na+-K+-ATPase of the retina. PMID- 6246023 TI - A new tumor model for angiographic investigations: feline sarcoma virus tumor induction in adult cats. AB - This article describes the first successful virus induction of sarcomas in adult immunosuppressed cats. The method of tumor induction, the immunosuppression regimen, and the gross, histologic, and angiographic findings in these induced sarcomas are described. The simplicity of the model, the rapid and reliable growth of the tumors, and the size of the animals permit repeated angiography. The model is well suited to studies of angiographically directed therapy with embolic agents, radioactive implants, or chemotherapeutic drugs. The use of a feline model permits repeated selective angiography, which is not the case with small laboratory animals, in which such studies are difficult. In this investigation, tumors were induced into the right hepatic lobe because of the relative homogeneity of peripheral hepatic vascularity and the ease with which early neoplastic changes can be detected. There is good evidence to indicate that virus induction sites in other organs would also be successful. PMID- 6246024 TI - Diffuse lung disease in a compromised host. PMID- 6246025 TI - Inhibitory effect on the formation of chlamydial inclusions in McCoy cells by seminal fluid and some of its components. AB - Our purpose was to determine the effect of semen and some of its components upon chlamydial inclusion (CI) count and cytopathogenic effect in cycloheximide treated McCoy cells. Semen and spermine caused a dose-related decrease in the number of CI, using a standardized infectious dose of Chlamydia trachomatis, immunotype F. Lysozyme in certain concentrations stimulated CI formation, whereas the cations Cu++ and Zn++ produced a cytopathogenic effect and a dose-related reduction of the CI count, EDTA neutralized the effects of the cations and its addition to seminal fluid experimentally infected with C. trachomatis resulted in a greater number of CI than found in control cultures containing only semen. PMID- 6246026 TI - Immunosuppression in experimental Junin virus infection of mice. AB - The effects of cyclophosphamide (CY), anti-mouse thymocyte sera, oxisuran, and cytosine arabinoside were evaluated in adult and newborn mice infected with Junin virus. Treatment with CY was the most effective, Adult mice, which are not normally susceptible to intracerebral infection with 10(3) LD50 of Junin virus, were rendered susceptible by treatment with an adequate dose and schedule of CY. However, CY-treated newborn mice were protected from death. This animal model may be suitable for use in pathogenesis and protection studies. PMID- 6246027 TI - Structural proteins of hand, foot and mouth disease viruses. AB - Coxsackievirus A16 (CA16) and enterovirus 71 (E71), which cause hand, foot and mouth disease, were compared with respect to their polypeptide composition by PAGE. Only three proteins were resolved for CA16, whereas the four characteristic structural proteins of E71, (VP1, VP2, VP3 and VP4) were separated. The distribution of labeled proteins suggested that the molecular weights of VP2 and VP3 of CA16 were very similar. The smallest protein, VP4, of CA16 and E71 had the same molecular weight, but the other proteins of the two serotypes were different in their molecular weights. PMID- 6246028 TI - In vitro production and titration assays of B-tropic retroviruses isolated from C57BL mouse tumors induced by radiation leukemia virus (RadLV-Rs): effect of dexamethasone. AB - The effect of dexamethasone (DXM) on the replication and titration assays of B ecotropic radiation leukemia virus (RadLV-Rs) isolates was examined. The drug was shown to enhance in vitro virus release by otherwise low producer permissive cells. DXM also stimulated infectivity and focus formation in murine S+L- permissive cells and shortened the time-appearance of virus-induced foci. In contrast to foci observed in nontreated cultures, which are generally abortive and composed of only a few morphologically transformed cells, those obtained with DXM were comparable to those induced by ecotropic retroviruses with a potent helper activity for murine sarcoma virus. In addition, DXM increased virus induced XC cell fusion. These fundamental data allowed a more abundant in vitro production of the B-ecotropic RadLV-Rs virus isolates as well as precise infectivity titration assays. PMID- 6246029 TI - Effect of six herpes simplex virus isolates on chromosomes of rabbit and hamster cell cultures. AB - The chromosome effect of 6 herpes simplex virus isolates in rabbit kidney (RK) and hamster embryo (HE) cell cultures was variable. However, each virus isolate produced similar rates of altered metaphases in RK and HE cell cultures 4 and 8 h after infection. The observations suggest an inverse relationship between frequency of chromosome aberrations and previously reported ability to biochemically transform rodent cells. PMID- 6246030 TI - Seroepidemiology of human syncytial virus: antibody prevalence in the Pacific. AB - A seroepidemiological survey of the human syncytial (foamy) virus was done by means of an indirect immunofluorescence test on 1,717 sera from nine different Pacific island territories. The specificity of the reaction was verified by neutralization tests. The study indicated that the virus is ubiquitous in this part of the world, with no region being entirely free of antibody. The antibody prevalence ranged from a low of 1.2% in Ponape to a high of 15.6% in the Cook Islands. The average prevalence for the nine insular communities was 6.9%. PMID- 6246031 TI - Portraits of viruses: bacteriophage lambda. PMID- 6246032 TI - Human immune response to proteins of cytomegalovirus. AB - A detergent extract of 35S-methionine-labeled cytomegalovirus(CMV)-infected cells was analyzed by crossed-immunoelectrophoresis using human sera with high anti-CMV antibody titers. Six distinct precipitation lines could be seen in agarose gels after crossed-immunoelectrophoresis. On further analysis of the precipitation lines using SDS-PAGE, the proteins obtained could be related to proteins identical in size, obtained from purified CMV nucleocapsids. PMID- 6246033 TI - Application of an immunoenzymatic method and an immunoautoradiographic method for a mass survey of nasopharyngeal carcinoma. AB - The frequency of IgA antibody to virus capsid antigen (VCA) of EB virus was tested by an immunoenzymatic method among adults in a mass serological screening of the general population of 6 communes in South China, as a guide toward early detection of nasopharyngeal carcinoma. Sera from 56 patients already recognized as having nasopharyngeal carcinoma (NPC) also were tested. The screening was conducted with sera from 56,584 persons age 30 years and older in Zangwu County in the Guangsi Zhuang Autonomous Region. IgA antibody to VCA was found in 96% of the NPC patients tested; the geometric mean antibody titer for this group was 1:41. The antibody also was detected in 117 of the persons surveyed in the mass screening, and among these, the geometric mean antibody titer was 1:21. 20 of the antibody-positive persons were diagnosed by clinical and pathological examination as having NPC. 18 of these cases were diagnosed soon after the initial tests in June-September, 1978, and an additional 2 were diagnosed only after follow-up examinations 10 months after the first blood sample was taken. All of the persons who are in the antibody-positive group but exhibit no detectable tumors are to be reexamined periodically. PMID- 6246034 TI - Effect of mitomycin C and hydroxyurea on the expression of the Epstein-Barr virus cycle following P3HR-1 superinfection. AB - Epstein-Barr virus (EBV) DNA synthesis following EBV P3HR-1 superinfection of the Burkitt lymphoma cell line, Daudi, is refractory to mitomycin C and hydroxyurea at concentrations which inhibit cell DNA synthesis to greater than 98% of control values. Further, neither mitomycin C nor hydroxyurea inhibit virus antigen synthesis following P3HR-1 superinfection. PMID- 6246035 TI - The genome-linked protein of picornaviruses. VI. The 5'-terminal protein of poliovirus type 2RNA is covalently linked to a nonanucleotide identical to that of poliovirus type 1 RNA. AB - Digestion of poliovirus type 2[32P]-RNA with enzymes and analysis of the products by column chromatography and paper electrophoresis provides evidence that the RNA is covalently linked to a small, basic protein, VPg, via a 5'-terminal pU residue. Digestion of the RNA with proteinase K followed by labeling of the peptidyl-RNA with the Bolton and Hunter reagent [iodinated 3-(4 hydroxyphenyl)propionic acid N-hydroxysuccinimide ester] yields 5'-labeled material suitable for rapid sequencing. The 5'-terminal sequence of poliovirion type 2 RNA was determined to be VPg-pUUAAAACAG... which is identical to the sequence at the 5'-terminus of the poliovirus type 1 genome. PMID- 6246036 TI - Effect of fibre from bran cereal on gastroenteropancreatic hormone responses of normal adults. PMID- 6246037 TI - Spindle cell atypical bronchial carcinoid. PMID- 6246038 TI - Absorption of actinide elements from the gastrointestinal tract of rats, guinea pigs and dogs. PMID- 6246039 TI - Absorption of actinide elements from the gastrointestinal tract of neonatal animals. PMID- 6246040 TI - Intramembranous particles on freeze-fractured membrane replica and sulfhydryl groups. AB - The correlated distribution of intramembranous particles and sulfhydryl groups was examined in normal adult rabbit erythrocyte ghosts. Ghosts were treated to exhibit characteristic patterns of particle distribution and sulfhydryl groups were stained with Fast Blue BBN. It was shown that particles and sulfhydryl groups were located in corresponding patterns. The results indicate that the intramembranous particles in the erythrocyte membrane consist predominantly of protein. PMID- 6246041 TI - [Alkaline phosphatase activity in the placental labyrinth of the cat and problems of specific localization of transport adenosine triphosphatase. An ultrastructural study (author's transl)]. AB - The ultrastructural localizations of alkaline phosphatase (ALPase) and of Na+-K+ dependent adenosine triphosphatase (Na+-K+-ATPase) were studied in the placental labyrinth of the cat during the last days of gestation. ALPase activity could be detected in the syncytiotrophoblast but was absent from maternal tissues. Enzyme activity was observed only along plasma membranes of microvilli and absorption tubules on the maternal surface of the syncytium and also on the podocytes-like cytoplasmic processes of the fetal face. The localization of the Na+-K+-ATPase activity as obtained with the method of Ernst was identical with that of ALPase. This activity was not very ouabaine sensitive or K+ dependent, but was almost completely inhibited by levamisole. The strong ALPase activity of the syncytiotrophoblast does not allow a specific detection of Na+-K+-ATPase. However, the localization of these enzymes activities on syncytiotrophoblast surfaces directly related to fetal and maternal capillaries could suggest that these surfaces are associated with transport mechanisms of the trophoblast. PMID- 6246043 TI - New directions in the education of minority nursing students. PMID- 6246042 TI - Localization of 3',5'-cyclic adenosine monophosphate phosphodiesterase (cAMP PDEase) activity in isolated bovine thyroid plasma membranes. AB - Isolated bovine thyroid plasma membrane preparations were obtained by isopycnic density gradient centrifugation. Cyclic AMP-PDEase (EC 3.1.4.c) activity has been demonstrated by electron microscopic histochemistry on the unit membrane of isolated bovine thyroid cells. 3-isobutyl-1-methyl-xanthine (IBMX) produced partial inhibition, while omission of the substrate revealed no reaction product deposition. These observations correlated well with biochemical studies that showed 0.4% of the total cAMP-PDEase activity to be present in the plasma membrane preparations. Kinetic analysis of cAMP hydrolysis yielded two apparent Michaelis constants for the homogenate and the plasma membrane-rich fraction. Dose-response curves for IBMX inhbition showed cAMP-PDEase of the homogenate to be more sensitive to inhibition than that of the plasma membrane-bound enzyme. Furthermore, wash experiments indicate that the plasma membrane-associated enzyme is tightly bound. This investigation strengthens our previous study and suggests that bovine thyroid cell plasma membranes contain a cAMP-PDEase that may be involved in interactions between the cell and the external environment in a manner yet to be determined. PMID- 6246044 TI - An interactional support group for graduate nursing students: a report. PMID- 6246045 TI - You too can prepare videotapes for instruction. PMID- 6246046 TI - Prediction of achievement in baccalaureate nursing education. PMID- 6246047 TI - The self-concept of undergraduate nursing students in relation to clinical performance and selected biographical variables. PMID- 6246048 TI - A peer group counseling model in nursing education. PMID- 6246049 TI - Games: an alternative to pedagogical instruction. PMID- 6246050 TI - Characteristics of the successful nursing student. PMID- 6246051 TI - Research: a vital component throughout the nursing curriculum. PMID- 6246052 TI - On becoming a nurse. PMID- 6246053 TI - Practical aspects of conducting a feasibility for graduate education in nursing. PMID- 6246054 TI - Toward the future: graduate education for professional nursing practice. PMID- 6246055 TI - Antidote for "reality shock". PMID- 6246056 TI - Analysis of nurses' knowledge of behavioral methods applied to chronic and acute pain patients. AB - Thirty-seven nurses with no formal training in behavioral methods were assessed on their knowledge of basic behavioral principles and terminology, the application of behavioral methods with chronic and acute pain patients to decrease negative and increase positive behaviors, and when and with which patients such methods should be applied. Results showed that nurses failed to exhibit adequate understanding of behavioral methods except for their application to decrease negative behavior. Findings are discussed in terms of documenting the need for formal training in behavioral methods as part of nurses' academic curriculum and targeting specific areas that should be emphasized as part of such training. PMID- 6246057 TI - Enhancing students' experience through the use of tape recordings. PMID- 6246058 TI - Guidelines for the identification or researchable problems. PMID- 6246059 TI - A program evaluation of four workshops designed to prepare nurse faculty in health assessment. PMID- 6246060 TI - Effect of sodium hydroxide treatment on rate of passage and rate of ruminal fiber digestion. AB - Ruminally fistulated lambs were used to measure the effect of sodium hydroxide treatment on rate of passage and rate of ruminal fiber digestion. Corncobs were raised to 60% moisture and treated to a final concentration of 0, 2.5, 5.0, 7.5 and 10.0% NaOH on a dry matter basis. The diets fed contained 80% cobs and 20% supplement, giving a complete mixed diet containing 0, 2.0, 4.0, 6.0 and 8.0% NaOH (dry basis). Chromic oxide was used as an external marker, and rumen samples were collected at 3, 6, 12, 24, 48 and 96 hr post-dosing. As level of NaOH treatment increased, rate of passage increased linearly (P less than .05). Mean ruminal retention time decreased from 32.4 hr for the control diet to 20.7 hr for the 8% NaOH diet. When rate of passage was regressed against NaOH level, the slope of the line was .142%/hr per unit NaOH, with r2 = .733. In another trial, sodium concentrations equal to the 4% NaOH diet were obtained by the addition of 7.3% NaCl to the basal diet. Rates of passage for lambs fed the diet containing NaCl were faster (P less than .05) than for lambs fed the control diet but slower (P less than .05) than for lambs on the 4% NaOH diet. These data suggest that both sodium intake and NaOH treatment affect rate of passage and are additive. Nylon bags containing .15 g cotton were used to measure the rate of ruminal fiber digestion in lambs fed the five NaOH-treated diets. Bags were removed from the rumen after 12, 24, 36 and 48 hr, and the loss in weight were used to estimate ruminal digestion. As level of NaOH increased, the rate of ruminal cotton digestion decreased linearly (P less than .05). When rate of cotton digestion was regressed against NaOH level, the slope of the line was -.488%/hr per unit NaOH, with r2 = .934. PMID- 6246061 TI - The attachment of bacteria to the gastric epithelium of the pig and its importance in the microecology of the intestine. PMID- 6246062 TI - Physical mapping of the Escherichia coli D-serine deaminase region: contiguity of the dsd structural and regulatory genes. AB - The genes dsdA, dsdO, and dsdC have been located on a 3.0-kilobase pair (kb) fragment of the Escherichia coli chromosome by a combination of techniques. The loci were first cloned onto lambda and various plasmid vectors. dsd hybrid plasmids were then digested with restriction enzymes, and the fragments were recloned to test for the presence of dsdC or dsdA. In one case, a 4.2-kb restriction fragment containing the dsdA operon was used to form a heteroduplex with a well-defined lambda dsd deoxyribonucleic acid. The results show that dsdA, dsdO, and at least 0.6 kb of dsdC are present on this piece of deoxyribonucleic acid. On the basis of the mapping analysis and the molecular weight of D-serine deaminase, 1.9 kb of the 4.2-kb fragment is accounted for by the three dsd loci. We conclude that dsdO and dsdC are contiguous. A detailed dsd restriction map is presented. PMID- 6246063 TI - Inititation and termination of chromosome replication in Escherichia coli subjected to amino acid starvation. AB - Initiation and termination of chromosome replication in an Escherichia coli auxotroph subjected to amino acid starvation were examined by following the incorporation of [3H]thymidine into the EcoRI restriction fragments of the chromosome. The pattern of incorporation observed upon restoration of the amino acid showed that starvation blocks the process of initiation prior to deoxyribonucleic acid synthesis within any significant portion of the EcoRI fragment which contains the origin of replication, oriC. In this experiment, no incorporation of [3H]thymidine into EcoRI fragments from the terminus of replication was observed, nor was it found when a dnaC initiation mutant was used to prevent incorporation at the origin which might have obscured labeling of terminus fragments. Thus amino acid starvation does not appear to block replication forks shortly before termination of replication. Attempted synchronization of replication initiation by including a period of thymine starvation subsequent to the amino acid starvation led to simultaneous incorporation of [3H]-thymidine into all EcoRI fragments within the 240-kilobase region that surrounds oriC. It is shown that the thymine starvation step allowed initiation and a variable, but limited, amount of replication to occur. PMID- 6246064 TI - Phosphatidylglycerophosphate synthease and phosphatidylserine synthase activites in Clostridium perfringens. AB - Cytidine 5'-diphospho (CDP)-1,2-diacyl-sn-glycerol (CDPdiacylglycerol):sn glycerol-3-phosphate phosphatidyltransferase (EC 2.7.8.5, phosphatidylglycero-P synthase) and CDPdiacylglycerol:L-serine O-phosphatidyltransferase (EC 2.7.8.8, phosphatidylserine synthase) activities were identified in the cell envelope fraction of the gram-positive anaerobe Clostridium perfringens. The association of phosphatidylglycero-P synthase and phosphatidylserine synthase with the cell envelope fraction of cell-free extracts was demonstrated by sucrose density gradient centrifugation, by both activities sedimenting with the 100,000 x g pellet and solubilization of both activities from the 100,000 x g pellet with Triton X-100. The pH optimum for both enzyme activities was 8.0 with tris(hydroxy methyl)aminomethane-hydrochloride buffer. Phosphatidylglycero-P synthase activity was dependent on magnesium ions (100 mM). Phosphatidylserine synthase activity was dependent on manganese (0.1 mM) or magnesium ions (50 mM). Both enzyme activities were dependent on the addition of the nonionic detergent Triton X-100. Maximum phosphatidylglycero-P synthase and phosphatidylserine synthase activities were obtained when the molar ratio of Triton X-100 to CDP-diacylglycerol was 50:1 and 12:1, respectively. The Km for sn-glycero-3-P in the phosphatidylglycero-P synthase reaction was 0.1 mM. The Km for L-serine in the phosphatidylserine synthase reaction was 0.15 mM. Both enzyme activities were 100% stable for at least 20 min at 60 degrees C. PMID- 6246065 TI - Subunit constituent of the porin trimers that form the permeability channels in the outer membrane of Salmonella typhimurium. AB - The polypeptide composition of the functional porin trimers that produced the permeability channels in the outer membrane of Salmonella typhimurium was examined on two-dimensional slab gels. The results suggested that the majority of porin trimers from strains producing mixed species of porin polypeptides consisted of homologous subunit polypeptides. The present results do not exclude the possibility that a small fraction of porin trimer is constructed from heterologous subunit polypeptides. PMID- 6246066 TI - New cryptic plasmid of Bacillus subtilis and restriction analysis of other plasmids found by general screening. AB - A new cryptic plasmid, pTA1030 (4.5 megadaltons, copy number 16), was characterized by restriction analysis, together with some other plasmids of Bacillus subtilis. PMID- 6246068 TI - Ultraviolet-endonuclease activity in cell extracts of Saccharomyces cerevisiae mutants defective in excision of pyrimidine dimers. AB - Cell-free extracts of ultraviolet-sensitive mutants of Saccharomyces cerevisiae defective in excision of pyrimidine dimers, rad1, rad2, rad3, rad4, rad10, and rad16, as well as the extracts of the wild-type strain RAD+, display ultraviolet endonuclease activity. PMID- 6246067 TI - Structural and physiological studies of the Escherichia coli histidine operon inserted into plasmid vectors. AB - A fragment of deoxyribonucleic acid 5,300 base paris long and containing the promoter-proximal portion of the histidine operon of Escherichia coli K-12, has been cloned in plasmid pBR313 (plasmids pCB2 and pCB3). Restriction mapping, partial nucleotide sequencing, and studies on functional expression in vivo and on protein synthesis in minicells have shown that the fragment contains the regulatory region of the operon, the hisG, hisD genes, and part of the hisC gene. Another plasmid (pCB5) contained the hisG gene and part of the hisD gene. Expression of the hisG gene in the latter plasmid was under control of the tetracycline promoter of the pBR313 plasmid. The in vivo expression of the two groups of plasmids described above, as well as their effect on the expression of the histidine genes not carried by the plasmids but present on the host chromosome, has been studied. The presence of multiple copies of pCB2 or pCB3, but not of pCB5, prevented derepression of the chromosomal histidine operon. Possible interpretations of this phenomenon are discussed. PMID- 6246069 TI - Control of cell septation by lateral wall extension in a pH-conditional morphology mutant of Klebsiella pneumoniae. AB - The pH-conditional morphology mutant of Klebsiella pneumoniae strain MirM7 grows as cocci at pH 7 and as rods at pH 5.8. The mutant has a high-level mecillinam resistance (50% lethal dose greater than 200 micrograms/ml) in both forms. When broth cultures of the rod-shaped mutant were grown with 0.7 microgram of mecillinam per ml, cells assumed a round shape and continued to divided at a higher rate than the untreated control. A MirM7 rod-shaped revertant (MirA12), when treated with the same antibiotic concentration, changed to coccal shape and stopped dividing. The penicillin-binding proteins (PBPs) of strains MirA12 and MirM7 were analyzed. K. pneumoniae had six major PBPs quite similar to those of Escherichia coli. No differences were seen in the PBPs of MirM7 cocci and rods and MirA12 cells. In particular, PBP2 was found to be present and similar in MirM7 rods and cocci and MirA12 cells. We suggest that that in gram-negative rods, a control mechanism exists which prevents further septation in the absence of lateral cell wall elongation. The unique behavior of MirM7 is due to the fact that the control mechanism is not active in this strain. This model allows us to explain the preservation of shape in bacterial rods under various conditions of growth and the mechanism of bacterial killing by mecillinam. PMID- 6246070 TI - Purification and characterization of specific 3-deoxy-D-manno-octulosonate 8 phosphate phosphatase from Escherichia coli B. AB - A phosphatase specific for the hydrolysis of 3-deoxy-d-manno-octulosonate (KDO)-8 phosphate was purified approximately 400-fold from crude extracts of Escherichia coli B. The hydrolysis of KDO-8-phosphate to KDO and inorganic phosphate in crude extracts of E. coli B, grown in phosphate-containing minimal medium, could be accounted for by the enzymatic activity of this specific phosphatase. No other sugar phosphate tested was an alternate substrate or inhibitor of the purified enzyme. KDO-8-phosphate phosphatase was stimulated three- to fourfold by the addition of 1.0 mM Co(+) or Mg(2+) and to a lesser extent by 1.0 mM Ba(2+), Zn(2+), and Mn(2+). The activity was inhibited by the addition of 1.0 mM ethylenediaminetetraacetic acid, Cu(2+), Ca(2+), Cd(2+), Hg(2+), and chloride ions (50% at 0.1 M). The pH optimum was determined to be 5.5 to 6.5 in both tris(hydroxymethyl)aminomethane-acetate and HEPES (N-2-hydroxyethylpiperazine-N' 2-ethanesulfonic acid) buffer. This specific phosphatase had an isoelectric point of 4.7 to 4.8 and a molecular weight of 80,000 +/- 6,000 as determined by molecular sieving and Ferguson analysis. The enzyme appeared to be composed of two identical subunits of 40,000 to 43,000 molecular weight. The apparent K(m) for KDO-8-phosphate was determined to be 5.8 +/- 0.9 x 10(-5) M in the presence of 1.0 mM Co(2+), 9.1 +/- 1 x 10(-5) M in the presence of 1.0 mM Mg(2+), and 1.0 +/- 0.2 x 10(-4) M in the absence of added Co(2+) or Mg(2+). PMID- 6246071 TI - Studies on functional domains of the regulatory subunit of bovine heart adenosine 3':5'-monophosphate-dependent protein kinase. AB - The functional domains of the regulatory subunit of isozyme II of cAMP-dependent protein kinase were studied. It was shown using Edman degradation that the regulatory subunit contained a phosphorylated residue which was very close in primary sequence to the site most sensitive to hydrolysis by low trypsin concentrations as postulated previously (Corbin, J.D., Sugden, P.H., West, L., Flockhart, D.A., Lincoln, T.M., and McCarthy, D. (1978) J. Biol. Chem. 253, 3997 4003). Catalytic subunit incorporated 0.9 mol of 32P from [gamma-32P]ATP into a preparation of regulatory subunit that contained 1.1 mol of endogenous phosphate. After phosphorylation by the catalytic subunit, the regulatory subunit contained 2.2 mol of chemical phosphate. The effects of heat denaturation upon the rate and extent of phosphorylation of the regulatory subunit were compared with the effects of these treatments upon the cAMP binding and inhibitory domains. These data suggested that the regulatory subunit required factors in addition to an intact phosphorylatable primary sequence in order for inhibitory activity to be expressed. Such factors might be part of the secondary or tertiary structure of the protein. These studies are discussed with respect to the mechanism of inhibition of catalytic activity, and a model of the regulatory subunit structure is proposed. PMID- 6246072 TI - In vivo studies on yeast cytochrome c methylation in relation to protein synthesis. AB - Methylation of cytochrome c was studied in vivo using double label with L-[methyl 3H]methionine and DL-[2-14C]methionine. In pulse-chase experiments the cytochrome c associated with the mitochondrial fraction possessed a higher ratio of 3H/14C label, suggesting the presence of methylated cytochrome c. The appearance of methylated cytochrome c in mitochondria showed no lag phase. The inhibition of cytochrome c methylation in presence of cycloheximide indicated that both the methylation and protein synthesis were tightly coupled and cycloheximide selectively inhibited cytochrome c methylation. There was also an indication of selective turnover of incorporation methyl groups in preformed cytochrome c. PMID- 6246073 TI - Structural basis for the conformational states of nitrosyl hemoglobins M Saskatoon and M Milwaukee. Influence of distal histidine residues on proximal histidine-iron bonds. PMID- 6246074 TI - The synthesis and properties of four spin-labeled analogs of adenosylcobalamin. AB - Four spin-labeled analogs of adenosylcobalamin have been synthesized to aid in the detection and identification of radical intermediates in the adenosylcobalamin-dependent enzymatic reactions and to serve as probes of the coenzyme, substrate, and effector binding sites of the protein. Three isomers of adenosylcobalamin, in which one of the propionamide side chains (b, d, or e) was hydrolyzed, and adenosylepicobalamin e-carboxylic acid were reacted with 4-amino 2,2,6,6-tetramethylpiperidine-N-oxyl in the presence of 1-ethyl-3-(3 dimethylaminopropyl)-carbodiimide to yield the spin-labeled adenosylcorrinoids. These spin-labeled derivatives of adenosylcobalamin function as coenzymes and/or inhibitors of dioldehydrase from Klebsiella pneumoniae and of ribonucleotide reductase from Corynebacterium nephridii. Electron spin resonance has been used to monitor the photolytic cleavage of the carbon-cobalt bond of these analogs. PMID- 6246075 TI - Differences among subfractions of H1 histone in retention of linear and superhelical DNA on filters. AB - Four kinds of rabbit thymus H1 histone differ among themselves in their ability to retain DNA on nitrocellulose filters. This is true for linear, or superhelical DNA, but the order of effectiveness of the different H1 histones depends on the physical conformation of the DNA. For linear DNA the binding efficiencies of the H1 histones are: RTL2 = RTL3 greater than RTL4 greater than RTL1. This order of effectiveness parallels the effectiveness of the H1 histones previously found for the condensation of linear DNA as observed by circular dichroism and viscosity. The binding efficiencies of the various histones toward superhelical DNA were: RTL4 greater than RTL3 greater than RTL1 greater than RTL2. The variation in amino acid sequence between different rabbit thymus H1 histones might thus introduce structural variations in nucleohistone fibers and perhaps in chromatin. PMID- 6246076 TI - The increase in bilayer fluidity of rat liver plasma membranes achieved by the local anesthetic benzyl alcohol affects the activity of intrinsic membrane enzymes. PMID- 6246077 TI - Purification and characterization of a poly(A)-specific exoribonuclease from calf thymus. AB - An exoribonuclease from calf thymus which specifically cleaves poly(A) in the single- or in the double-stranded form has been isolated and purified to homogeneity. The enzyme has a molecular weight of about 80,000 as estimated by gel filtration, and consists of two subunits with molecular weights of 58,000 and 31,000 as analyzed by sodium dodecyl sulfate-gel electrophoresis. For optimal activity, the poly(A)-specific exoribonuclease requires divalent cations, alkaline pH, and 39 degrees C. The enzyme is inhibited at 0.2 ionic strength and is sensitive to reagents for thiol groups. The only product formed by the action of the enzyme is 5'-AMP. It is suggested that this enzyme plays a role in the degradation of the poly(A) sequence of mRNA in the nucleus. PMID- 6246078 TI - Physical characteristics of hyaluronate binding to the surface of simian virus 40 transformed 3T3 cells. AB - The binding of labeled hyaluronate to the surface of Simian virus 40-transformed 3T3 cells was studied as a function of 1) pH, 2) ionic strength, 3) temperature, and 4) molecular weight of the hyaluronate. Binding occurred over a wide range of pH values with optima at pH 7 and at less than pH 4. Binding at low pH was eliminated at high ionic strength whereas that at physiological pH was enhanced, with a maximum at 0.5 M NaCl. The enhancement of binding at pH 7 was reversible and independent of the particular salt used. Scatchard plot analysis showed that increasing the ionic strength resulted in both a decrease in the dissociation constant (Kd) and an increase in the amount bound at saturation (Bmax). Temperature also influenced the binding of hyaluronate to the cell surface. The amount bound at low temperatures (0 degrees C) was 3 to 5 times that bound at high temperatures (40 degrees C) with a sharp transition occurring at 18 degrees C, the temperature of phase transition of the plasma membrane. The temperature effect was primarily a change in the Bmax and was reversible. Finally the molecular weight of the ligand influenced the binding. High molecular weight preparations of hyaluronate had a higher binding affinity (lower Kd) and a lower Bmax than did smaller molecular weight preparations. PMID- 6246079 TI - Heterogeneity of radioligand binding to alpha-adrenergic receptors. Analysis of guanine nucleotide regulation of agonist binding in relation to receptor subtypes. PMID- 6246080 TI - Adrenodoxin reductase . adrenodoxin complex. Rapid formation and breakdown of the complex and a slow conformational change in the flavoprotein. PMID- 6246081 TI - Comparison of the binding sites on cytochrome c for cytochrome c oxidase, cytochrome bc1, and cytochrome c1. Differential acetylation of lysyl residues in free and complexed cytochrome c. AB - The isolated complexes of ferricytochrome c with cytochrome c oxidase, cytochrome c reductase (cytochrome bc1 or complex III), and cytochrome c1 (a subunit of cytochrome c reductase) were investigated by the method of differential chemical modification (Bosshard, H.R. (1979) Methods Biochem. Anal. 25, 273-301). By this method the chemical reactivity of each of the 19 lysyl side chains of horse cytochrome c was compared in free and in complexed cytochrome c and binding sites were deduced from altered chemical reactivities of particular lysyl side chains in complexed cytochrome c. The most important findings follow. 1. The binding sites on cytochrome c for cytochrome c oxidase and cytochrome c reductase, defined in terms of the involvement of particular lysyl residues, are indistinguishable. The two oxidation-reduction partners of cytochrome c interact at the front (exposed heme edge) and top left part of the molecule, shielding mainly lysyl residues 8, 13, 72 + 73, 86, and 87. The chemical reactivity of lysyl residues 22, 39, 53, 55, 60, 99, and 100 is unaffected by complex formation while the remaining lysyl residues in positions 5, 7, 25, 27, 79, and 88 are somewhat less reactive in the complexed molecule. 2. When bound to cytochrome c reductase or to the isolated cytochrome c1 subunit of the reductase the same lysyl side chains of cytochrome c are shielded. This indicates that cytochrome c binds to the c1 subunit of the reductase during the electron transfer process. PMID- 6246082 TI - Regulation of fatty acid synthetase concentration and activity during adipocyte differentiation. Studies on 3T3-L1 cells. PMID- 6246083 TI - An electron paramagnetic resonance study of the high and low spin forms of chloroperoxidase. PMID- 6246084 TI - Epidermal growth factor-receptor-protein kinase interactions. Co-purification of receptor and epidermal growth factor-enhanced phosphorylation activity. AB - Membranes may be prepared from A-431 human epidermoid carcinoma cells which have the ability to bind 125I-labeled epidermal growth factor (EGF) in a specific manner and which, in the presence of EGF, catalyze the phosphorylation of a number of endogenous membrane proteins. The activation of the membrane associated protein kinase by EGF appears to be a reversible phenomenon. The membrane preparation may be solubilized by a number of nonionic detergents with the retention of both 125I-labeled EGF-binding activity and EGF-enhanced phosphorylation of specific membrane proteins. The solubilized membrane preparation may be purified by affinity chromatography using EGF covalently linked to Affi-Gel. The purified preparation retains both EGF-binding activity and EGF-enhanced phosphorylation activity. Analysis of the affinity-purified preparation by sodium dodecyl sulfate-gel electrophoresis indicates the presence of one major protein band of molecular weight 150,000 and several trace bands. The evidence suggests that the major 150,000 protein band is the receptor for EGF and is a substrate of the phosphorylation reaction. The co-purification of EGF binding activity and EGF-stimulated phosphorylation activity suggests an inherent close relationship. PMID- 6246085 TI - Complicated organization of a single repeated DNA sequence in the chicken genome is revealed by cloning. AB - The structural organization of a family of repeated DNA sequences in the chicken genome has been determined by hybridization of a cloned repeated DNA sequence to Southern blots of total DNA. The length of the cloned DNA fragment is 3600 nucleotide pairs. This fragment consists principally, if not entirely, of a single repeated DNA sequence occurring only once within the cloned fragment. In the chicken genome, the family of repeated DNA sequences homologous to the cloned sequence has a limited number of alternative forms. Some of the restriction fragments of total DNA to which the cloned sequence hybridizes correspond to those expected from the location of restriction endonuclease cleavage sites within the cloned sequence. There are also a limited number of other genomic restriction fragments, each present in multiple copies, to which the cloned sequence hybridizes but which do not relate in any obvious way to the length of the cloned sequence. These various restriction fragments differ from one another in that they appear to be present in unequal amounts in total DNA, and many of them do not contain the entire cloned sequence. This study provides some new information about the structure of repeated DNA sequences in the chicken genome. The copies of a repeated DNA sequence may differ from one another both by minor variations in nucleotide sequence (divergence) and in more substantial ways as would be expected to arise from processes such as insertion, deletion, and translocation. In addition to this description of a single cloned repeated DNA sequence from the chicken genome, this paper reports the cloning of more than 100 different restriction fragments of chicken DNA, each of which contains one or more repeated DNA sequences. PMID- 6246086 TI - A cloned chicken DNA fragment includes two repeated DNA sequences with remarkably different genomic organizations. AB - The presence of both single copy sequences and repeated DNA sequences with a broad range of repetition frequency is a hallmark of the eukaryotic genome. The advent of recombinant DNA technology has made it possible to isolate cloned DNA fragments that encompass two or more DNA sequences with different repetition frequencies. This provides the first opportunity to investigate the structural relationships in the genome of DNA of the different repetition frequency classes in a thorough and systematic way. A cloned fragment of the chicken genome containing two different repeated DNA sequences has been used for this purpose. By hybridization of radioactive restriction fragments of the cloned DNA to filter bound restriction fragments of total chicken DNA, it has been determined that the 5.5-kilobase inserted DNA in this clone contains a copy of each of two long, repeated DNA sequence elements with different repetition frequencies. These two repeated DNA sequences have very diverse arrangements in the chicken genome. The results establish that, in addition to the interspersion of single copy and repeated DNA sequences in the chicken genome, repeated DNA sequences with very different structural characteristics can be interspersed with one another. Thus, the chicken genome is a complex network of related sequences in which some members of a family of repeated DNA sequences are associated with other, nonhomologous repeated DNA sequences, while other members of the same family are flanked by single copy DNA. PMID- 6246087 TI - Influence of fatty acyl substitution on the composition and function of macrophage membranes. PMID- 6246088 TI - Potassium- and ionophore A23187-induced discharge of secretory protein in guinea pig pancreatic lobules. Role of extracellular calcium. AB - Elevated concentrations of potassium chloride (50 to 120 mM) in the incubation medium stimulated in vitro discharge of secretory protein from guinea pig pancreatic lobules. The effect of potassium was not inhibited by 10(-4) M atropine, sodium substitutes, or 10(-5) M tetrodotoxin. Exposure of lobules to elevated concentrations of potassium chloride did not increase the release of tissue lactic dehydrogenase and resulted in the appearance of exocytotic images detected by electron microscopy. The time course and extent of discharge due to 75 mM KCl were similar to those caused by the ionophore A23187 and the secretory effect of both agents depended on extracellular calcium and intracellular energy reserves. Potassium chloride stimulation of 75 mM increased the influx of extracellular calcium by 49%, as measured by net 45Ca uptake. Optimal carbamylcholine chloride or pancreozymin stimulation consistently showed a greater effect on discharge than optimal KCl or A23187 stimulation and the additional effect depended on the ability of these physiological secretagogues to recruit calcium from intracellular sources. Potassium chloride stimulation did not result in cyclic GMP elevations in the presence of atropine and those elevations due to A23187 stimulation were small (21 to 30%) and dissimilar both in character (calcium dependence) and time course compared to those resulting from the physiological secretagogues. These findings allow us to define two interrelated pathways which couple hormonal stimulation and discharge of secretory protein in the exocrine pancreas. PMID- 6246089 TI - Transcription of simian virus 40 DNA by wheat germ RNA polymerase II. Priming of RNA synthesis by the 3'-hydroxyl of DNA at single strand nicks. AB - Linear simian virus 40 DNA has been transcribed in vitro with wheat germ RNA polymerase II. Transcription products have been fractionated on polyacrylamide gels and several discrete sized RNA bands are seen. The RNA band pattern is affected dramatically by deoxyribonuclease treatment during RNA isolation. This is because most of the RNA synthesized is covalently linked to DNA. This linkage has been demonstrated by density analysis in formaldehyde-CsCl gradients and by incorporation of alkali-stable ribonucleotides into DNA. The linear DNA templates transcribed were generated by treatment of circular DNA with restriction enzymes which, in addition to cutting once at a single primary site, were found also to produce single strand nicks at specific secondary sites. The discrete sized RNA bands observed result from initiation at these nicks and terminated at DNA ends. There are two modes of nick-dependent initiation. In one mode the 3'-hydroxyl terminus of the DNA at a single strand nick serves as a primer for the extension of an RNA chain. In a second mode de novo initiation of an RNA chain is promoted at the nick. RNAs which are not primed initiate predominantly with GTP. The catalytic action of wheat germ RNA polymerase II is similar to that of Escherichia coli core RNA polymerase which has also been shown to synthesize primarily RNA which is covalently linked to DNA. PMID- 6246090 TI - Decatenation of kinetoplast DNA by topoisomerases. AB - Kinetoplast DNA is the mitochondrial DNA of trypanosomatids such as Crithidia fasciculata. This DNA is in the form of networks containing thousands of DNA circles which are apparently catenated (interlocked). Some topoisomerases, such as T4 phage topoisomerase and DNA gyrase, catalyze a decatenation of the networks to form individual covalently closed circles. PMID- 6246091 TI - A new copper(II) electron paramagnetic resonance signal in two laccases and in cytochrome c oxidase. AB - A new EPR signal from Cu2+ has been discovered in reductive experiments with type 2 copper-depleted laccase from Polyporus versicolor. A novel EPR signal has also been found in native laccase from Rhus vernicifera on oxidation of the reduced protein with H2O2. In reoxidation experiments with cytochrome c oxidase from beef heart, a new Cu2+ signal has been observed. With Rhus laccase, the new signal is shown to originate from one of the copper ions that are nondetectable in the resting enzyme, and evidence is presented for the signals in Polyporus laccase and cytochrome c oxidase also stemming from the metal pairs that are antiferromagnetically coupled in the oxidized enzymes. The new signals show strong rhombic character, and the EPR parameters place them in a category different from the signals of type 1 as well as of type 2 Cu2+ ions. PMID- 6246092 TI - Evidence for a 1,25-dihydroxyvitamin D3 receptor-like macromolecule in rat pituitary. PMID- 6246093 TI - Reconstitution of turkey erythrocyte beta-adrenergic receptors into human erythrocyte acceptor membranes. Demonstration of guanine nucleotide regulation of agonist affinity. AB - Digitonin-solubilized turkey erythrocyte beta-adrenergic receptors were reconstituted by dialysis into human erythrocyte acceptor membranes which lack beta receptors. Incorporation of turkey beta receptors into acceptor membranes was directly proportional to the quantity of soluble protein added to the reconstitution system. Reconstituted beta receptors demonstrate saturable [125I]iodohydroxybenzylpindolol binding (Bmax = 11.1 +/- 0.8 fmol/mg, K = 77.8 +/ 8.6 pM) and stereospecificity ((-)-propranolol, K = 11.0 nM; (+)-propranolol, K = 2000 nM; (-)-isoproterenol, K = 250 nM; (+)-isoproterenol, K = 82 micro M). Reconstituted beta receptors appear to be incorporated into acceptor membranes as integral proteins. Reconstituted beta receptors cannot be extracted by high salt or pH (3 to 11); detergent is required for resolubilization of reconstituted beta receptors. Adenylate cyclase stimulation was not obtained in reconstituted membranes since acceptor membranes lack a catalytic subunit. However, guanine nucleotide regulation of agonist affinity was observed indicating a functional reconstitution. GTP (100 micro M) produces a 5-fold decrease in the affinity of isoproterenol for reconstituted beta receptors. Experiments with sulfhydryl reagents indicate that the reconstituted beta receptor couples with the guanine nucleotide regulatory protein of the acceptor membranes. These data describe the successful reconstitution of a beta receptor and indicate that the reconstituted beta receptor can interact with the GTP binding protein of human erythrocyte acceptor membranes. PMID- 6246094 TI - A carbon-centered free radical intermediate in the prostaglandin synthetase oxidation of arachidonic acid. Spin trapping and oxygen uptake studies. AB - The ESR spin-trapping technique has been used to identify a free radical involved in the oxygenation of arachidonic acid by ram seminal vesicle microsomes. The ESR spectrum of the radical adduct indicates that a carbon-centered arachidonic acid free radical has been observed. The formation of this species is inhibited by indomethacin, but not by phenol, and it is probably the first intermediate formed during the prostaglandin synthetase-catalyzed oxidation of arachidonic acid. The chemical identity of the trapped radical was substantiated with an independent synthesis of a closely related radical adduct. PMID- 6246095 TI - Stimulation of phosphorylase b kinase by the calcium-dependent regulator. PMID- 6246096 TI - The regulation of carbamyl phosphate synthetase (ammonia) in rat liver mitochondria. Effects of acetylglutamate concentration and ATP translocation. PMID- 6246097 TI - Different sidedness of functionally homologous essential thiols in two membrane bound phosphotransferase enzymes of Escherichia coli detected by permeant and nonpermeant thiol reagents. AB - The membrane-bound Enzyme IIbgl and IIglc are both inactivated in vivo by the sulfhydryl reagent N-ethylmaleimide. The former is also inhibited by the hydrophilic sulfhydryl reagents p-chloromercuribenzoic acid and p mercuriphenylsulfonic acid, while the latter is resistant to these reagents. However, inhibition of this enzyme is observed after impairment, either transient or permanent, of the permeability barrier of bacterial envelopes. Since p chloromercuribenzoic acid and p-chloromercuriphenylsulfonic acid are able to cross the outer membrane of Escherichia coli, their failure to inhibit in vivo Enzyme IIglc must be due to their inability to cross the inner membrane of the bacteria. It would therefore appear that sensitive thiol group(s) of Enzyme IIglc and Enzyme IIbgl, in spite of their functional similarity, exhibit opposite orientation within the cytoplasmic membrane, the first enzyme having an -SH group accessible from the outer surface of the membrane, while the second has an -SH group accessible from the inner surface of the membrane. The present results strengthen the view that these two enzymes have in asymmetric orientation within the membrane as already suggested by their vectorial function. PMID- 6246098 TI - Isolation and characterization of the novel polyadenylate- and polyuridylate degrading acid endoribonuclease V from calf thymus. AB - A novel endoribonuclease was detected and purified to homogeneity from calf thymus. The homogeneity was checked by analysis in polyacrylamide gels (both in the presence and in the absence of sodium dodecyl sulfate) as well as by isoelectric focusing. This nuclease activity, which is called Endoribonuclease V, cleaves poly(A) and poly(U); other single- or double-stranded synthetic polyribo- as well as polydeoxyribonucleotides are not degraded. Endoribonuclease V cleaves poly(A) to create first oligoribonucleotides and ultimately 3'-AMP; no P-2':3' Ado degradation products were detected. The enzyme has a pH optimum of 5.8, an isoelectric point of pH 6.3, a molecular weight of 52,300, and requires neither monovalent nor divalent cations. The enzyme activity is not inhibited by N ethylmaleimide. PMID- 6246099 TI - Induction of Epstein-Barr virus-associated DNA polymerase by 12-O tetradecanoylphorbol-13-acetate. Purification and characterization. AB - The diterpene ester promoter of mouse skin tumors, 12-O-tetradecanoylphorbol-13 acetate (TPA), efficiently induces Epstein-Barr virus (EBV)-associated DNA polymerase (DNA nucleotidyltransferase) activity in the EBV-producing lymphoblastoid cell line, P3HR-1. With the use of intervent dilution chromatography followed by sequential DEAE-cellulose and phosphocellulose column chromatography, the virus-associated enzyme has been isolated and purified 300 fold. The partially purified EBV DNA polymerase activity could be distinguished from cellular polymerases by its activation with salt and its degree of sensitivity to N-ethylmaleimide and phosphonoacetic acid. The enzyme showed maximum activity for copying activated calf thymus DNA in the presence of 100 mM ammonium sulfate. In the absence of salt, the enzyme utilized with high efficiency deoxyoligomer-homopolymer templates, but failed to copy poly(rA) . oligo(dT)10 and oligo(dT)10, showing that the enzyme had properties distinct from DNA polymerase gamma, reverse transcriptase, and terminal deoxynucleotidyltransferase. The partially purified enzyme is strongly inhibited by acyclovir triphosphate and thus has properties similar to herpes simplex virus DNA polymerase. PMID- 6246100 TI - Inhibition of lysosomal phospholipase A and phospholipase C by chloroquine and 4,4'-bis(diethylaminoethoxy) alpha, beta-diethyldiphenylethane. PMID- 6246101 TI - Properties of a reconstituted vitamin D3 25-hydroxylase from rat liver mitochondria. PMID- 6246102 TI - Human placental adenosine kinase. Kinetic mechanism and inhibition. AB - The kinetic properties of human placental adenosine kinase, purified 3600-fold, were studied. The reaction velocity had an absolute requirement for magnesium and varied with the pH. Maximal activity was observed at pH 6.5 with a Mg2+:ATP ranging from 1:1 to 2:1. High concentrations of Mg2+ or free ATP were inhibitory. Double reciprocal plots of initial velocity studies yielded intersecting lines for both adenosine and MgATP2-. The Michaelis constant was 0.4 micro M for adenosine and 75 micro M for MgATP2-. Inhibition by adenosine was observed at concentrations greater than 2.5 micro M. AMP was a competitive inhibitor with respect to adenosine and a noncompetitive inhibitor with respect to ATP. ADP was a noncompetitive inhibitor with respect to adenosine and ATP. Hyperbolic inhibition was observed during noncompetitive inhibition of adenosine kinase by AMP and ADP. Other purine and pyrimidine nucleoside mono-, di-, and triphosphates were poor inhibitors in general. S-Adenosylhomocysteine and 2'-deoxyadenosine inhibited adenosine kinase. The data suggest that (a) MgATP2- is the true substrate of adenosine kinase, and both pH and [Mg2+] may regulate its activity; (b) the kinetic mechanisms of adenosine kinase is Ordered Bi Bi; and (c) adenosine kinase may be regulated by the concentrations of its products, AMP and ADP, but is relatively insensitive to other purine and pyrimidine nucleotides. PMID- 6246103 TI - Short term regulation of ureagenesis. AB - In order to examine the mechanism of the acute response of ureagenesis to amino acid loads, rats were injected intraperitoneally with various doses of a mixture of 20 amino acids. Blood ammonia rose only slightly with doses of 0.5 to 2.0 g/kg, but increased sharply at doses of 3 to 5 g/kg. Carbamyl phosphate synthetase I (EC 2.7.2.5) activity, assayed in intact mitochondria isolated from livers removed 15 min after injection of amino acids, with N-acetylglutamate at its endogenous levels, rose up to 5-fold with increasing doses up to 2 g/kg; no further activation occurred with larger doses. This maximal activity was the same as the activity measured in disrupted mitochondria. Hepatic levels of glutamate and N-acetylglutamate increased approximately linearly with dose of amino acids. The time course of these changes following a dose of 1.5 g/kg was studied. Glutamate, N-acetylglutamate, and carbamyl phosphate synthetase I activity all peaked 5 to 15 min after injection. All of these results were virtually unaltered by omission of arginine from the injected mixture, indicating that the increase in N-acetylglutamate was not attributable to activation by arginine of N acetylglutamate synthetase. These results indicate that moderate loads of amino acids activate unreagenesis via a rapid increase in N-acetylglutamate levels, secondary to increased mitochondrial glutamate, and independently of injected arginine. This autoregulatory mechanism becomes saturated at large doses of amino acids, and hyperammonemia then supervenes. PMID- 6246104 TI - The insulin-mimetic effects of vanadate in isolated rat adipocytes. Dissociation from effects of vanadate as a (Na+-K+)ATPase inhibitor. PMID- 6246105 TI - Purification to homogeneity of H blood group beta-galactoside alpha 1 leads to 2 fucosyltransferase from porcine submaxillary gland. AB - A beta-galactoside alpha 1 leads to 2 fucosyltransferase has been solubilized from porcine submaxillary glands and purified 124,000-fold to homogeneity by repeated affinity chromatography on GDP-hexanolamine agarose. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of the purified enzyme revealed two electrophoretic species with apparent Mr = 60,000 and 55,000. The two enzyme species have not been completely resolved, but both appear to be active forms of the fucosyltransferase with approximately equal specific activities. Glycosidase digestion of the fucosylated products with the alpha 1 leads to 2-specific fucosidase from Clostridium perfringens and the alpha 1 leads to 3/alpha 1 leads to 4-specific fucosidase from almond emulsin indicates that the enzyme forms exclusively the Fuc alpha 1 leads to 2Gal linkage with a variety of acceptor substrates. A GDP-fucose hydrolase activity co-purifies with the fucosyltransferase. Identical rates of thermal inactivation and co-migration on gel electrophoresis under nondenaturing conditions suggest that the two activities are due to a single enzyme species. PMID- 6246106 TI - Bulk membrane fluidity increases after fertilization or partial activation of sea urchin eggs. AB - Membrane fluidity increases within 10 min after fertilization of Strongylocentrotus purpuratus and Lytechinus pictus eggs as detected by a decrease in order parameter of the spin label fatty acid 5-doxylstearate. The magnitude of this change is proportional to the fraction of fertilized eggs present. The order parameter decreases when unfertilized eggs are partially activated by ammonia treatment but does not change when the extracellular coats are removed. The increase in membrane fluidity, therefore, appears to be a "late" event in the fertilization program. The increase in fluidity is confined to the polar head group region of the membrane bilayer. Spectral and autoradiographic analyses indicate that the spin label resides in lipid bilayers throughout the cell. Thus, these measurements apply to bulk cell membranes. Detectable changes in lipid composition do not occur shortly after fertilization. PMID- 6246107 TI - Resolution of hormone-sensitive triglyceride/diglyceride lipase from monoglyceride lipase of chicken adipose tissue. PMID- 6246108 TI - Hormonal regulation of cyclic AMP binding to specific receptor proteins in rat ovarian follicles. Characterization by photoaffinity labeling. PMID- 6246109 TI - Electrophorus electricus (Na+ + K+)-ATPase. Evidence for simultaneous Na+ and K+ binding in the presence of Pb2+. PMID- 6246110 TI - Effects of GTP on choleragen-catalyzed ADP ribosylation of membrane and soluble proteins. AB - Choleragen-dependent ADP ribosylation of soluble proteins from bovine thymus, using [32P]NAD as substrate, was increased 3- to 4-fold by GTP. The effect was specific for nucleoside triphosphate, with GTP approximately equal to ITP greater than CTP greater than ATP greater than UTP. Half-maximal enhancement was observed with 0.5 mM GTP. The magnitude of the GTP effect decreased with increasing NAD concentration; GTP had no effect on hydrolysis of NAD at low NAD concentrations. Digestion of ADP-ribosylated proteins with snake venom phosphodiesterase yielded primarily 5'-AMP. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of soluble proteins from thymus after incubation with choleragen and [32P]NAD separated numerous ADP-ribosylated proteins; radioactivity in all bands was increased by nucleoside triphosphate. Choleragen catalyzed the ADP ribosylation of several purified proteins; depending on the protein, GTP either increased, decreased, or had no effect on the extent of ADP ribosylation. Choleragen dependent ADP ribosylation of a wide variety of proteins is consistent with the possibility that intoxication results in covalent modification of more than one cellular protein and perhaps alters the activity of other enzymes in addition to adenylate cyclase. PMID- 6246111 TI - Dicyclohexylcarbodiimide binds specifically and covalently to cytochrome c oxidase while inhibiting its H+-translocating activity. AB - We have investigated the covalent binding of dicyclohexylcarbodiimide (DCCD) to cytochrome c oxidase in relation to its inhibition of ferrocytochrome c-induced H+ translocation by the enzyme reconstituted in lipid vesicles. DCCD bound to the reconstituted oxidase in a time- and concentration-dependent manner which appeared to correlate with its inhibition of H+ translocation. In both reconstituted vesicles and intact beef heart mitochondria, the DCCD-binding site was located in subunit III of the oxidase. The apolar nature of DCCD and relatively minor effects of the hydrophilic carbodiimide, 1-ethyl-(3 dimethylaminopropyl)-carbodiimide, on H+ translocation by the oxidase indicate that the site of action of DCCD is hydrophobic. DCCD also bound to isolated cytochrome c oxidase, though in this case subunits III and IV were labeled. The maximal overall stoichiometries of DCCD molecules bound per cytochrome c oxidase molecule were 1 and 1.6 for the reconstituted and isolated enzymes, respectively. These findings point to subunit III of cytochrome c oxidase having an important role in H+ translocation by the enzyme and indicate that DCCD may prove a useful tool in elucidating the mechanism of H+ pumping. PMID- 6246112 TI - Thyrotropin receptors in normal human thyroid. Nonclassical binding kinetics not explained by the negative cooperativity model. AB - Saturation analysis of equilibrium binding of iodinated thyrotropin (125I-TSH) to normal human thyroid preparations yielded linear Scatchard plots under non physiological conditions of pH 6.0 or 20 mM Tris/acetate buffer, pH 7.4. The apparent equilibrium dissociation constant of this binding was approximately 10( 8) M. By contrast, nonlinear plots were obtained under standard conditions of pH 7.4 and 40 mM Tris/acetate buffer. Resolution of the components of these curves by computer analysis revealed the presence of at least two classes of binding sites, one of which is of a low capacity and high affinity (approximately 10(-10) M) consistent with receptor binding. The other component is of a high capacity and lower affinity. Binding to non-target tissues of muscle, parathyroid, mammary carcinoma, and placenta was only demonstrable at pH 6.0 or in 20 mM Tris/acetate buffer, pH 7.4, yielding linear Scatchard plots with similar binding affinity (approximately 10(-8)M) to normal thyroid but much reduced capacity. Preincubation of thyroid tissue at 50 degrees C resulted in an apparent selective loss of the high affinity component of binding measured under standard conditions. Kinetic experiments on the dissociation of bound 125I-TSH were undertaken to determine whether the non-linearity of Scatchard plots was due to two or more classes of binding sites or negative cooperativity. It was found that the experimental determinant that is presently ascribed to a negative cooperativity phenomenon regulating receptor affinity (i.e. an enhanced dilution induced dissociation rate in the presence of excess native hormone), although apparently hormone-specific, was demonstrated under nonphysiological binding conditions and in non-target tissue. Significantly, the phenomenon was found under conditions of pH 6.0 or 20 mM Tris where a linear Scatchard plot was obtained. The evidence thus suggests that 125I-TSH binds to heterogeneous binding sites (of which the high affinity is probably the receptor for TSH) and that the enhanced dilution-induced dissociation of bound hormone by native hormone for this system, is only a characteristic of the low affinity binding site (maybe gangliosides). PMID- 6246113 TI - Mechanism of T4 phage restriction by plasmid Rts 1. Cleavage of T4 phage DNA by Rts 1-specific enzyme. PMID- 6246114 TI - The role of calmodulin in the regulation of protein phosphorylation and insulin release in hamster insulinoma cells. PMID- 6246115 TI - Purification and characterization of a ferredoxin from Rhizobium japonicum bacteroids. AB - An eight-iron, eight-sulfur ferredoxin from Rhizobium japonicum bacteroids of soybean root nodules has been purified to apparent homogeneity as judged by disc gel electrophoresis. The purification procedure included chromatography on DEAE cellulose, Bio-Gel P-60, and hydroxylapatite. Specific activities of several purified preparations of bacteroid ferredoxin ranged from 1700 to 1900 nmol of C2H4 produced . min-1 . mg-1 in the reaction mediating electron transfer between illuminated chloroplasts and bacteroid nitrogenase. A molecular weight of 6740 for the protein was determined by low speed sedimentation equilibrium and a molecular weight of 6500 was estimated from the mobility of bacteroid ferredoxin relative to the mobility of standard proteins during sodium dodecyl sulfate disc gel electrophoresis. All of the common amino acids were present except arginine, methionine, and tryptophan. The absorbance spectrum of the oxidized protein exhibited maxima at 285 nm and 380 nm with a shoulder near 305 nm. The A380/A285 ratio was 0.76 and the extinction coefficient at 380 nm for the oxidized protein was found to be 30,800 M-1. Equilibration of bacteroid ferredoxin with methyl viologen at various potentials revealed a midpoint oxidation-reduction potential of -484 mV. Spectrophotometric examination of iron-sulfur clusters extruded from bacteroid ferredoxin with benzenethiol and the transfer of its iron-sulfur clusters to other ferredoxins established the presence of two [4Fe-4S] clusters in a molecule of bacteroid ferredoxin. The EPR spectrum of oxidized ferredoxin consisted of a small signal at g = 2.02 integrating to 0.19 spin/molecule. The EPR spectrum of ferredoxin reduced with 5-deazaflavin exhibited a signal with features at g values of 1.88, 1.94, 2.01, and 2.07, and integrated to 1.7 spins/molecule. The EPR properties of bacteroid ferredoxin are characteristic of a ferredoxin operating between the 1+ and 2+ oxidation levels. Bacteroid ferredoxin mediated electron transfer to clostridial hydrogenase, but was not reduced by the clostridial phosphoroclastic system in the presence of pyruvate. Bacteroid ferredoxin reduced by illuminated 5-deazariboflavin also supported a high rate of C2H2 reduction by bacteroid nitrogenase which was free of Na2S2O4. It was concluded, on this basis, that bacteroid ferredoxin has the capability of functioning as the electron donor for nitrogenase in R. japonicum. PMID- 6246116 TI - Optimal spatial requirements for the location of basic residues in peptide substrates for the cyclic AMP-dependent protein kinase. AB - The specificity of the cyclic AMP-dependent protein kinase was examined using two series of dodecapeptides as substrates. One series consisted of peptides of the general sequence (Gly)x-Arg-Arg-(Gly)y-Ala-Ser-Leu-Gly in which x + y = 6. The other series consisted of peptides of the sequence (Gly)x-Lys-Arg-(Gly)y-Ala-Ser Leu-Gly in which x + y was again equal to 6. The peptides Gly-Gly-Gly-Gly-Gly-Gly Gly-Arg-Arg-Ser-Leu-Gly and Gly-Gly-Gly-Gly-Gly-Gly-Gly-Lys-Arg-Ser-Leu-Gly were also examined. In the series in which the adjacent arginines were located various distances from the serine, the substrate for which the enzyme clearly exhibited optimal kinetic constants contained one amino acid residue between the basic residues and serine. Direct binding studies of N alpha-[3H]acetyl peptides to catalytic subunit of cyclic AMP-dependent protein kinase revealed a correlation between binding affinity and the ability to serve as substrate for the enzyme. In the second series in which the adjacent basic amino acids were Lys-Arg, optimal kinetic constants were again obtained when these residues were separated from serine by a single amino acid. This latter result was surprising in view of phosphorylation site sequences in the known physiologically significant protein substrates for the kinase, since those containing Lys-Arg all contain two amino acids between these residues and serine. PMID- 6246117 TI - Flavin analogs as mechanistic probes of adrenodoxin reductase-dependent electron transfer to the cholesterol side chain cleavage cytochrome P-450 of the adrenal cortex. AB - The intrinsic isotope effect on the reduction of the FAD-containing dehydrogenase electron transferase, adrenodoxin reductase, by (4S)-[2H]NADPH has been determined to be 7.1 to 7.7. The replacement of FAD by a series of FAD analogs at the active site of adrenodoxin reductase with oxidation-reduction potentials which vary over a range of 212 mV has made it possible to extrapolate to this limiting value from the variation in the observed isotope effect on Vmax with flavin midpoint potential. Stop-flow studies which allow the direct determination of the intrinsic isotope effect on the reductive half-reaction corroborate this result. During the steady state reduction of ferricyanide by the native enzyme under conditions of Vmax, this isotope effect is almost fully expressed (VH/VD = 6.7 to 6.8). In contrast, we observe a dramatic attenuation of the intrinsic isotope effect (due to hydride transfer to flavin) when the oxidative half reaction is mediated by the natural acceptor protein, the 2Fe/2S ferredoxin, adrenodoxin. In a coupled three-protein system, the adrenodoxin-mediated reductions of both the artificial electron acceptor, cytochrome c, and the physiological electron acceptor, cytochrome P-450scc, by adrenodoxin reductase occur at similar rates and with similar kinetic isotope effects (1.9 to 2.0) when (4S)-[2H]NADPH is the reductant. We infer similar mechanisms for the reduction of both cytochromes. These results are in agreement with previous studies (Lambeth, J.D., and Kamin, H. (1979) J. Biol. Chem. 254, 2766-2774) which show that the reductive half-reaction is not solely rate-determining in adrenodoxin-mediated processes. The observation of a linear free energy relationship between Vmax and the flavin midpoint potential during steady state reduction of ferricyanide confirms that the reductive half-reaction is rate-determining in this assay. The relationship between Vmax and flavin midpoint potential in reactions which require adrenodoxin suggests that the midpoint potential of native adrenodoxin reductase has been optimized. Thus, the apoenzyme of adrenodoxin reductase tailors the midpoint potential of bound FAD in order to balance the activation energies of the reductive and oxidative half-reactions. PMID- 6246118 TI - Processing of prolactin by human breast cancer cells in long term tissue culture. AB - Two human breast cancer cell lines (T-47D and MCF-7) and one cell line derived from normal human milk (HBL-100) not only specifically bound but also degraded prolactin. Quantitative differences in the ability to bind and degrade prolactin among the cell lines exist, although there was a good correlation between the number of prolactin receptor sites and prolactin degradative activity. Iodo prolactin as well as native prolactin were degraded. The prolactin molecule was processed to yield at least three small molecular weight peptides which were released into the incubation medium. These peptides neither bound to fresh receptors nor to anti-prolactin antibodies. The protease inhibitor N-alpha-p tosyl-L-lysine chloromethyl ketone, lysosomotropic agents such as chloroquine and ammonium chloride, and metabolic inhibitors 2,4-dinitrophenol and sodium azide, all abolished prolactin degradation by the breast cancer cells. When prolactin degradation was inhibited, specific binding and the subsequent release of intact 125I-prolactin was still observable, suggesting that hormonal degradation was not a prerequisite to dissociation of prolactin. However, prolactin degradation did account for the accelerated rate of dissociation of prolactin. Studies utilizing inhibitors suggest that the receptor-bound 125I-prolactin was degraded by an energy-dependent internalization process such as pinocytosis; lysosomal enzymes are probably involved in the degradation of prolactin by human breast cancer cells. PMID- 6246119 TI - On the possible role of serotonin in the regulation of regeneration of cilia. AB - A study was made of the interrelationship of serotonin, cAMP, and calcium ions in the regulation of regeneration of cilia by Tetrahymena pyriformis. All these compounds stimulated the regeneration, whereas a blocker of serotonin synthesis, p-chlorophenylalanine, and a calcium chelator, EGTA, inhibited the process. This inhibition could be overcome by the addition of any of the stimulatory compounds. cAMP was also found to be inhibitory at high concentrations. The intracellular concentration of this nucleotide was found to increase during the regeneration, and this increase occurred precociously in the presence of serotonin. It was concluded that serotonin may regulate ciliary regeneration by a mechanism involving cAMP And calcium ions, but that the causal relationships among these compounds still need to be established. PMID- 6246120 TI - [3H]ouabain autoradiography of frog retina. AB - The kinetics and distribution of ouabain binding in retinas of Rana pipiens were examined quantitatively by scintillation counting and freeze-dry autoradiography. The time-course of binding at several concentrations was consistent with a bimolecular reaction. Estimated equilibrium binding levels gave a Michaelis Menton relationship with a Km = 8.3 x 10(-8) M and a maximum binding level (Bmax) = 4.4 x 10(-8) mol/g protein. The distribution of binding sites measured autoradiographically varied considerably between layers. The photoreceptor, inner plexiform, and optic nerve fiber layers exhibited the heaviest binding. Within the photoreceptor layer, binding was nonuniform. Binding in the outer segment decreased distally, averaging approximately 4% of that in the proximal receptor layers (Bmax = 4.6 x 10(-6) M). The origin of the outer segment activity is uncertain at light microscope resolution, as it may be a result of inner segment calyceal processes. Binding within the proximal receptor layers was also nonuniform. Several peaks were observed, with those at the inner segment and synaptic layers being especially noticeable. Assuming an absence of glial cell binding in the proximal receptor layers, we calculated there to be 13 x 10(6) ouabain or Na+,K+ pump sites per rod receptor. Limited measurements suggest a Bmax of approximately 8 x 10(-6) M for the inner plexiform layer. PMID- 6246122 TI - A possible role for cyclic AMP in the initiation of DNA synthesis by isoproterenol-activated parotid gland cells. PMID- 6246121 TI - Cell-substratum attachment and cell surface hyaluronate of Rous sarcoma virus transformed chondrocytes. AB - Hyaluronate is associated with the cell surface of cultured Rous sarcoma virus transformed chondrocytes. Detachment of these cells from their substratum by a variety of reagents is accompanied by release of 75-100% of this hyaluronate into solution. Treatment of the cells with 200 U/ml protease-free Streptomyces hyaluronidase at 37 degrees C cause release of greater than 90% of the cell surface hyaluronate and complete cell detachment. Treatment with a lower concentration of Streptomyces hyaluronidase (30 U/ml) at 25 degrees C or a corresponding activity of testicular hyaluronidase gives similar results, but only in the presence of mM EGTA. Treatment with the lower activities of either hyaluronidase or with 1 mM EGTA alone release only approximately 45% of the cell surface hyaluronate and does not cause significant cell detachment. It is concluded that there are two populations of cell surface hyaluronate differing in their accessibility or their resistance to dissociation from other components of the cell surface. It is proposed that the less readily released fraction is located between the transformed chondrocyte surface and substratum and is necessary for their interaction. PMID- 6246123 TI - A synergistic effect of glucocorticoids and insulin on the differentiation of myoblasts. AB - Glucocorticoids and insulin were found to act synergistically to promote differentiation in some clones of the L6 rat myoblast cell line. Other hormone effects on these cells were investigated to determine the extent of the synergism. The insulin stimulation of sugar transport was unaffected by glucocorticoids although they did by themselves slightly enhance transport. Glucocorticoids were found to increase the adhesiveness of the cells--an effect not influenced by insulin. Cyclic AMP levels were found to peak just prior to the time of the onset of fusion and insulin broadened this peak, while the combination of both hormones further lengthened the time for which cyclic AMP levels remained elevated. PMID- 6246124 TI - Effect of phagocytosis on guinea pig granulocyte membrane markers. PMID- 6246125 TI - Concanavalin A induces an intraluminal alkalinization of thymocyte membrane vesicles. AB - Weak acid distribution methods demonstrate that mitogenic levels of concanavalin A induce an intravesicular alkalinization of isolated thymocyte membrane vesicles. Experiments with chemical reagents that crosslink the high affinity concanavalin A receptor and extensive correlation with known cellular events suggest that a "membrane Bohr effect" may participate in the initiation of mitogenesis. PMID- 6246126 TI - Growth-modulating tripeptide (glycylhistidyllysine): association with copper and iron in plasma, and stimulation of adhesiveness and growth of hepatoma cells in culture by tripeptide-metal ion complexes. AB - The tripeptide H-Gly-His-Lys-OH (GHL) is a human plasma constituent which has been previously shown to modulate the growth and viability of a variety of cell types and organisms. Experimental observations presented herein indicate that GHL is complexed with the transition metal ions Cu++ and Fe++ in vivo and may exert its biological effects as a peptide-metal chelate. At physiological pH in vitro, GHL associates with ionic copper, cobalt, iron, molybdenum, manganese, nickel, and zinc, but has no affinity for calcium, manganese, potassium, and sodium. GHL acts synergistically with copper, iron, cobalt, and zinc to alter patterns of cell growth in monolayer cultures of a tumorigenic hepatoma cell line (HTC4). These transition metals induce cellular flattening and adhesion to support surfaces, and inhibit DNA synthesis and lactic acid production when growth is limited by reduction of serum concentrations in medium. These inhibitory effects are neutralized, and intercellular adhesion and growth are stimulated by GHL in medium at nanomolar concentrations. Cu and Fe are the most active metals when combined with GHL. The results suggest that the inability of HTC4 cultures to replicate without adequate concentrations of serum in medium may reflect deficiency of GHL and transition metals, which appear to form complexes prior to interaction with cells. Chelation of transition metals with GHL and, potentially, with other growth-modulating peptide factors in plasma or medium, may provide a mechanism for expression and regulation of biological activities influenced by transition metals and polypeptide growth factors. The observed effects of GHL metal complexes, including stimulation of cellular adhesiveness to substratum (flattening) and intercellular attachment (monolayer formation), appear to satisfy requirements for growth of hepatoma cells in monolayer culture. PMID- 6246127 TI - Isolation and characterization of a morphologic variant of Chinese hamster (CHO) cells. AB - An epithelioid clone of Chinese hamster (CHO) cells which is spontaneously transformed was exposed to the mutagen N-methyl-N-Nitro-N-Nitrosoguanidine (MNNG), and a fibroblastic variant, clone CHO-F2, was isolated. This clone is partially reverted in several of the in vitro properties characteristic of transformed cells. When compared to wild type CHO, CHO-F2 has a longer doubling time, a lower saturation density and less piling up at high cell density, and a higher serum requirement. CHO-F2 also elaborates less plasminogen activator and has more abundant microtubules and actin cables. On the other hand, both CHO and CHO-F2 grow in agar suspension (although CHO-F2 grows with a lower efficiency), both lack detectable LETS protein, and both are tumorigenic in nude mice. Thus, expression of the individual properties frequently associated with transformation and tumorigenicity can be dissociated. The most critical biochemical change in CHO-F2 appears to be an increase in the intracellular level of cyclic AMP, when compared to CHO, and several growth and morphological properties of CHO-F2 resemble those induced in wild type CHO exposed to exogenous dibutyryl cyclic AMP. The role of cyclic AMP in expression of the transformed phenotype and the significance of individual in vitro parameters of transformation with respect to tumorigenicity are discussed. PMID- 6246128 TI - The suppression of cellular proliferation in SV40-transformed 3T3 cells by glucocorticoids. AB - Glucocorticosteroids, when added two hours after cell plating to SV40 transformed, 3T3 mouse fibroblasts in low serum (0.3% v/v), biotin-supplemented medium, suppress cellular proliferation by 24 hours. While some cell death probably occurs, the growth inhibition is not primarily due to cytotoxicity and cytolysis. This conclusion is supported by the following: 1) both dead and viable cell numbers are suppressed, 2) little cell debris is evident in the medium, and 3) very high concentrations of glucocorticoids do not cause an increase in the dead cell count. Furthermore, this growth suppression, which is specific for glucocorticoids since several non-glucocorticoid steroids have no inhibitory effect, is not permanent nor irreversible. Removal of the glucocorticoid and replacement with 10% serum restore rapid proliferation. Although higher concentrations (1% and 10%) of serum afford some protection against glucocorticoid inhibition, this protection is not simply a consequence of faster growth rates. SV3T3 cells can be grown in serum-free medium supplemented with biotin, transferrin, insulin, and epidermal growth factor (EGF). Under these conditions growth rates are comparable to high serum media, yet glucocorticoids are still powerful inhibitors. However, the omission of insulin from serum-free, glucocorticoid cultures does result in observable cell death and lysis. Flow microfluorometry and autoradiographic studies have determined that glucocorticoid inhibited cells are partially blocked in G1. The proportions of S phase and G2 + M cells are greatly reduced with an accompanying accumulation of G1 cells. These results suggest that glucocorticoids regulate a biochemical step(s) in G1 which is critical for DNA initiation. PMID- 6246129 TI - Hexose uptake enhancing factor released from Rous sarcoma cells. AB - Conditioned media from Rous sarcoma virus transformed chicken embryo fibroblasts stimulate the uptake of 2-deoxyglucose in normal chicken fibroblasts. The factor responsible for this effect, which is also shed in very low amount by non transformed fibroblasts, is destroyed by trypsin and not linked to the protease and plasminogen activator activities present in the media. Its apparent molecular weight, determined by gel filtration, is about 20,000 daltons. The factor released by transformed cells might be related to the monomeric form of a family of glucose binding and transport proteins recently reported by Lee and Lipmann ('78) to be detached by detergents from normal and transformed cells. PMID- 6246130 TI - Sarcoma growth factor (SGF): specific binding to epidermal growth factor (EGF) membrane receptors. AB - Cells transformed by murine sarcoma viruses (MSV) produce and release into their tissue culture media several polypeptide growth stimulating factors. One of these has been partially purified using Bio-Gel P-60 column chromatography followed by DEAE-cellulose chromatography. This growth factor was assigned the name sarcoma growth factor (SGF), and is here shown to require the epidermal growth factor (EGF) receptor in order to function as a growth factor. DEAE-cellulose chromatography yielded a product that was several-fold purer than the material present in the Bio-Gel P-60 column pool II. The biologically active material from the DEAE-cellulose column, when labeled with 125I, showed specific binding to EGF membrane receptors. The specific binding could be prevented with the addition of either unlabeled EGF or SGF. Both radiolabeled SGF and EGF will bind to live or fixed cells. We were able to bind 125I-SGF as well as 125I-EGF to fixed cells and elute the bound material from fixed receptors. The eluted SGF showed a greater than 25-fold increase in specific binding. The biological activities of EGF and SGF could be bound to and eluted from fixed receptors. The eluted SGF showed a greater than 25-fold increase in specific binding. The biological activities of EGF and SGF could be bound to and eluted from fixed cells. A 3T3 clone lacking EGF receptors was unable to respond to either EGF or SGF, whereas it responded well to serum and several other purified growth factors. The SGF isolated using DEAE-cellulose chromatography was unable to compete in a radioimmune assay using 125I-EGF and antibody to purified mouse submaxillary gland EGF; it also was not precipitated by anti-EGF antibody. From these studies it appears that the SGF produced and released by these MSV-transformed cells combines with and requires the EGF receptor in order to exert its biological effects. The peptide, however, is antigenically distinct from mouse submaxillary gland EGF. PMID- 6246131 TI - Chemosensitivity of single smooth muscle cells to acetylcholine, noradrenaline, and histamine in vitro. AB - Electrical responses to acetylcholine, noradrenaline, and histamine were recorded from solitary smooth muscle cells. Iontophoresis of each transmitter elicited three fast responses: a hyperpolarization, a depolarization, or a biphasic hyperpolarization-depolarization. Each transmitter activated a specific receptor since responses were specifically blocked by antagonists, two transmitters elicited different responses in solitary cells, and desensitization of response to one transmitter did not cause desensitization of responses to other transmitters. Responses were due to increased ion conductances since input resistance decreased during responses and reversal potentials were measured for depolarizing responses (-5 mV) and hyperpolarizing responses (-60 mV). Regional differences in transmitter sensitivity were mapped on solitary cells. Biphasic responses were due to simultaneous activation of receptors mediating hyperpolarizing responses and receptors mediating depolarizing responses which were segregated in the cell membrane. Noradrenaline enhanced action potential amplitude by regulation of voltage-dependent ion conductances. Finally, noradrenaline and histamine elicited periodic hyperpolarizing potentials, which may be due to increased intracellular Ca++. PMID- 6246132 TI - Determination of mecillinam in urine by reversed-phase high-performance liquid chromatography. PMID- 6246133 TI - Familial male pseudohermaphroditism due to 17-20-desmolase deficiency. I. In vivo endocrine studies. AB - In two siblings with male pseudohermaphroditism (ambiguous external genitalia, XY karyotype) and apparently normal glucocorticoid function, plasma concentrations of 10 progestagens or androgens measured by specific RIAs were found to be abnormal under either basal or dynamic conditions. Basal levels of delta 4 androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone sulfate were subnormal and failed to rise after ACTH stimulation both before and after castration. Meanwhile, levels of pregnenolone, pregnenolone sulfate, 17 alpha hydroxyprogesterone, and 17 alpha-hydroxypregnenolone were extremely high under basal conditions and rose further after ACTH. All of the progestagens and cortisol were suppressed by dexamethasone. After hCG stimulation, either before treatment or during dexamethasone therapy, the rise in testosterone was less than 100 ng/dl, while the progestagens showed an abnormally high rise. The latter were markedly reduced after castration. These findings are consistent with steroid 17- 20-desmolase deficiency in both the testes and adrenal glands. In the third brother, who had only slight abnormalities of his genitalia, a mild form of the same defect was suspected. Low androgens, high 17 alpha-hydroxypregnenolone, and 17 alpha-hydroxyprogesterone levels were found in the amniotic fluid and umbilical cord and peripheral blood at birth. The parents, who were not consanguine, had normal baseline levels of all hormones. The familial occurrence of the disease is suggestive of autosomal recessive inheritance. PMID- 6246134 TI - Mineral metabolism in diabetes mellitus: changes accompanying treatment with a portable subcutaneous insulin infusion system. PMID- 6246135 TI - Regulation of steroid secretion by adrenal tissue of a human anencephalic fetus. AB - ACTH-stimulated adrenal tissue of a human anencephalic fetus, when maintained in organ culture, secreted appreciable quantities of cortisol but little dehydroisoandrosterone sulfate or pregnenolone sulfate. In the absence of ACTH, cortisol secretion was severely attenuated. Arginine vasopressin or alpha MSH, when added to the culture medium, did not stimulate steroid secretion. When whole human serum was present in the culture medium bathing the adrenal tissue of the anencephalic fetus, the rate of cortisol secretion was similar to that attained when lipoprotein-poor serum was in the medium. Based on these findings, it is concluded that in the presence of ACTH, the adrenals of the anencephalic fetus secrete principally cortisol, and the failure of dehydroisoandrosterone sulfate and pregnenolone sulfate secretion is due to the absence of the fetal zone. The lack of stimulation of cortisol secretion by lipoprotein is probably due to a reduced number of low density lipoprotein receptors resulting from diminished ACTH stimulation before birth. PMID- 6246136 TI - Adult-onset vitamin D-resistant osteomalacia with the unresponsiveness to parathyroid hormone. AB - Serum immunoreactive parathyroid hormone (PTH) levels were increased in a 50-yr old man with a unique variant of adult-onset vitamin D-resistant osteomalacia, presenting with high phosphate clearance, mild hypocalcemia, and blunted hypercalcemic and phosphaturic responses to exogenous parathyroid extract. After normalization of his serum calcium level with a large amount of 1 alpha hydroxycholecalciferol, a synthetic vitamin D analog, serum PTH levels and phosphate clearance returned to normal, and hypercalcemia as well as phosphaturia appeared when parathyroid extract was administered. Further studies demonstrated that the renal response could be restored by the administration of calcium with the suppression of PTH. The evidence presented suggests that the resistance of PTH in this patient was due to secondary hyperparathyroidism rather than to a defect of PTH-sensitive receptors of the kidney and bone or to inadequacy of vitamin D per se. PMID- 6246137 TI - Congenital hypothyroidism associated with thyrotropin unresponsiveness and thyroid cell membrane alterations. PMID- 6246138 TI - Evidence for increased dopaminergic and opioid activity in patients with hypothalamic hypogonadotropic amenorrhea. PMID- 6246139 TI - Coexistence of pituitary adrenocorticotropin-dependent Cushing's syndrome with a solitary adrenal adenoma. AB - A 45-yr-old woman presented with a 2-hr history of Cushing's syndrome. Baseline cortisol and ACTH levels were elevated and lacked a normal circadian rhythm. Dynamic testing of her pituitary-adrenal function revealed positive responses to metyrapone and synthetic ACTH and suppression with high doses of dexamethasone. The finding of asymmetrical adrenal uptake of 6-[131I]methyl-19-nor-cholesterol and a tumor image in the right adrenal on venography led to the preoperative diagnosis of pituitary ACTH-dependent adrenal hyperfunction coexisting with a right adrenal adenoma. Surgical resection of the right adrenal demonstrated a solitary 39-g nodule, 4 cm in diameter. There were no additional nodules present in the surrounding cortex. When incubated in vitro, both the adenoma and the surrounding tissue were functional and responsive to ACTH. This was in contrast to the lack of response to ACTH in vitro of similar tissues removed from two other patients with ACTH-independent adrenal adenomas. We suggest that this case represents a transition between pituitary ACTH-dependent bilateral adrenocortical hyperfunction and solitary adrenal adenoma. PMID- 6246140 TI - Impaired cortisol secretion in abetalipoproteinemia. AB - In the adrenal gland cholesterol for steroid biosynthesis is derived from both de novo biosynthesis and receptor mediated uptake of plasma low density lipoproteins (LDL). In the present study we have compared ACTH stimulated adrenal production of cortisol in four control subjects and one adult male patient with abetalipoproteinemia, a disorder in which LDL is absent. Basal morning cortisol levels in the plasma in the control subjects (13.3 +/- 1.6 microgram/dl) and abetalipoproteinemic patient (14.6 micrograms/dl) were similar. During infusion of alpha 1, 24 ACTH however, plasma cortisol levels were higher in the control subjects than in the abetalipoproteinemic patient and this difference was significant at times after 4 hours. Urinary excretion of both 17-hydroxy and 17 ketosteroids over the 24 hour infusion period was also significantly lower in the abetalipoproteinemia patient indicating that cortisol production rates were reduced. Our results suggest that in the absence of plasma low density lipoproteins, as occurs in abetalipoproteinemia, the maximal production of adrenal corticosteroids is impaired. By inference, these findings lend in vivo support to the view that plasma low density lipoproteins serve as an important source of cholesterol for adrenal steroidogenesis in man. PMID- 6246141 TI - Immunohistological studies of nonthyroidal calcitonin-producing tumors. AB - A series of oat cell carcinomas of the lung and some corresponding sputum specimens were studied along with other tumors by immunoperoxidase histology for the presence of calcitonin, beta-endorphin, and ACTH. Sixteen of 31 tissues were positive for calcitonin, 12 of 14 were positive for beta-endorphin, and 11 of 14 were positive for ACTH immunoreactivity. Many tissues contained all 3 peptides, and in some sections these peptide immunoreactivities appeared to be present in the same cells. These studies suggest that there is a releationship in oat cell carcinoma of the lung and other tumors among the 3 peptides, although the basis of this relationship is not clear. PMID- 6246142 TI - Plasma glycoprotein hormone alpha-subunit in the syndrome of gonadal dysgenesis: the effect of estrogen replacement in hypergonadotropic hypogonadism. PMID- 6246143 TI - Pituitary carcinoma mimics the ectopic adrenocorticotropin syndrome. AB - A middle-aged man presented with weight loss, hypokalemic alkalosis, diabetes, hypertension, and generalized melanosis. Marked elevation of urinary free cortisol (655 micrograms/24 h) and plasma ACTH (2445 PG/ML) SUGGESTED THE DIAGNOSIS OF ECTOPIC ACTH syndrome. The plasma concentrations of cortisol and urinary 17-hydroxycorticosteroids increased paradoxically during the administration of dexamethasone without a corresponding change in the plasma ACTH level. Metyrapone administered over 24 h also markedly incrased both urinary free cortisol and 17-hydroxycorticosteroids. Selective venous sampling of plasma ACTH did not reveal a gradient between jugular vein and peripheral venous blood. The laboratory findings supported the diagnosis of ectopic ACTH syndrome. However, belated occurrence of visual changes necessitated surgical exploration, resulting in the diagnosis of pituitary carcinoma. A fluorescent antibody to ACTH reacted strongly with the atypical pituitary cells. This rare case documents that severe melanosis in Cushing's disease can occur without prior adrenalectomy and is consistent with the diagnosis of pituitary carcinoma. Furthermore, melanosis observed in patients with pituitary carcinoma is associated with ACTH levels similar to those occurrring in the ectopic ACTH or Nelson's syndrome. PMID- 6246144 TI - Effect of iodine enrichment in vitro on the adenylate cyclase-adenosine 3',5' monophosphate system in thyroid glands from normal subjects and patients with Graves' disease. PMID- 6246145 TI - Differential regulation of thyrotropin releasing hormone receptors in neoplastic rodent mammotropic, adrenocorticotropic and thyrotropic pituitary cells in culture. AB - Modulation of the concentration of receptors for thyrotropin releasing hormone (TRH) is different in neoplastic mammotropic, adrenocorticotropic, and thyrotropic pituitary cells in culture. Hydrocortisone increases the TRH receptor concentration in mammotropic and adrenocorticotropic cells but has no effect in thyrotropic cells. B-estradiol increases the TRH receptor number in mammotropic cells but has no effect in adrenocorticotropic and thyrotropic cells. Both TRH and T3 decrease the receptor concentration in all three cell types. PMID- 6246146 TI - Evidence for gamma-MSH-like immunoreactivity in ectopic ACTH-producing tumors. AB - Using a specific radioimmunoassay for gamma-MSH, a predicted peptide in the cryptic N-terminal portion of the adrenocorticotropin-beta-lipotropin precursor, gamma-MSH-like immunoreactivity (gamma-MLI) was detected in two ectopic ACTH producing tumors. Gel chromatographic studies on Bio-Gel P-60 revealed one or two peaks of gamma-MLI; one was eluted near th elution position of beta-LPH, compatible with gamma-MLI in human pituitary and the other emerged near the position of beta-endorphin. These results indicate that ectopic ACTH-producing tumors eleborate not only ACTH, beta-endorphin but also gamma-MLI. PMID- 6246147 TI - Enzyme-linked immunosorbent assay for mumps and parainfluenza type 1 immunoglobulin G and immunoglobulin M antibodies. AB - A solid-phase enzyme-linked immunosorbent assay (ELISA) for detection of mumps and parainfluenza type 1 antibodies (immunoglobulin G [IgG] and IgM classes) is described and compared with the conventional complement fixation (CF) test. A highly positive correlation was found between mumps IgG ELISA and the mumps CF test, whereas parainfluenza type 1 IgG ELISA had only a moderate positive correlation with the respective CF test. Mumps IgM antibodies could be demonstrated in all patients with serologically verified and clinically typical (parotitis, meningitis, or orchitis) mumps virus infection, but not in patients with rises in parainfluenza CF titers. Mumps IgM was already present in the acute phase sera if they were not taken during the first 2 days after onset of disease. Mumps IgM was also found in some paired sera that were taken too late to demonstrate any significant increase in the antibody titers by CF. Therefore, mumps IgM ELISA provides an improvement over the conventional laboratory diagnosis of mumps infection, since the measurement of specific IgM antibodies in a single serum by ELISA is diagnostic, rather than the identification of a fourfold or greater rise in CF antibody titer. An unexpected finding was that parainfluenza type 1 IgM antibodies could not be demonstrated by ELISA in paired sera with rises in parainfluenza CF titers, suggesting a different antibody response from that occurring in mumps infection. PMID- 6246148 TI - Flavor preexposures in a conditioned taste aversion situation: a dissociation of behavioral and endocrine effects in rats. AB - A series of experiments examined the effects of flavor preexposures on pituitary adrenal/behavior relations in a conditioned taste aversion paradigm. It was found that reexposure to a novel milk solution paired earlier with lithium chloride (LiCl) elicited conditioned activation of the pituitary-adrenal system (Experiment 1). The unconditioned response to LiCl (measured by changes in plasma levels of corticosterone) did not vary as a function of prior (2 and 5 vs. 10) exposures to the milk solution (Experiment 2). Increased familiarity with the substance (resulting from 10 prior exposures) rendered the conditioning of a taste aversion to this substance less effective. Further, reexposure to this familiar substance after its pairing with LiCl was not accompanied by the characteristic conditioned pituitary-adrenal activation (Experiment 3). By titrating the number of conditioned stimulus (CS) preexposures (Experiment 4) it was found that within the range of preexposures manipulated (5-10), subjects exhibited (a) a coupling of behavioral and pituitary-adrenocortical responses when the conditioned taste aversion to the milk solution was paralleled by elevated plasma corticosterone (5-6 preexposures), (b) a coupling of these two response systems when flavor consumption was accompanied by suppressed plasma titers of corticoids (9-10 preexposures), or (c) a dissociation of the two system when the conditioned taste aversion was not accompanied by conditioned adrenocortical activity (7-8 preexposures). These data are discussed in terms of a dissociation in the effects of CS preexposures on conditioned adrenocortical and behavioral response systems. PMID- 6246150 TI - Malignant glomus jugulare tumor: a case with two unusual radiographic features. AB - The computed tomographic demonstration of a glomus jugulare tumor with two unusual radiographic features--multiple pulmonary metastases and extension of the tumor into the cerebellopontine angle--is presented. PMID- 6246149 TI - Experimental glioma in primates: a computed tomography model. AB - Owl and squirrel monkeys inoculated intracerebrally with human polyomavirus obtained from the brain of patient with progressive multifocal leukoencephalopathy developed cerebral gliomas. Among these tumors, three out of five were detected and accurately localized by contrast enhanced computed tomography (CT) when the animals were still clinically normal. Various CT features of these tumors corresponded to specific pathologic changes, such as histologic type and presence of hemorrhage and necrosis. Also, tumor progression was clearly demonstrated in repeat scans of one animal. The CT sensitivity and the capability of distinguishing various pathologic features are encouraging. It appears that a much needed, suitable model of experimental cerebral tumors in primates is now available for CT studies. PMID- 6246151 TI - Activation of the alternative pathway of complement: a mechanism in search of diseases. PMID- 6246152 TI - Immunoglobulin E-mediated asthma and hypersensitivity pneumonitis with precipitating anti-hapten antibodies due to diphenylmethane diisocyanate (MDI) exposure. AB - Two workers are presented who were exposed to diphenylmethane diisocyanate (MDI) while coating pipes with a polyurethane foam. After a latent period of exposure, worker A developed immediate-onset asthma and worker B developed a clinical picture of hypersensitivity pneumonitis for which he was hospitalized. The antibody response of these workers to a conjugate of MDI with human serum albumin (MDI-HSA) was measured by gel precipitation, total antibody binding of 125I MDI HSA, and specific IgG and IgE antibody by polystyrene-tube radioimmunoassay (PTRAI). Worker B had precipitating antibody to MDI-HSA by double immunodiffusion in gel. Both workers had high levels of IgG antibody specific for MDI-HSA which had some cross-reactivity with a conjugate or toluene diisocyanate and HSA. Total serum antibody binding of 125I MDI-HSA was 15 microgram/ml in worker A and 900 microgram/ml in worker B. Both workers had serum IgE antibody specific for MDI HSA as measured by two PTRIA techniques. These results indicate that a marked immunologic response to MDI is possible in exposed workers and that hypersensitivity pneumonitis can occur subsequent to the inhalation of a low molecular-weight chemical in the industrail setting. PMID- 6246153 TI - Influenza: epidemiology, etiology, immunization and management. AB - Influenza, an acute contagious respiratory infection caused by orthomyxoviruses A, B, and C, occurs in local outbreaks, epidemics and pandemics. Differences in the morphology and antigen patterns for these viruses account for the differences in virulence and immunity. Influenza A is virulent, B is mild, and C is nonvirulent. Swine influenza virus may spread from swine to man (recycling of human A virus), causing epidemics and pandemics. The 1976-77 influenza vaccination program involved swine virus, and was associated with 321 cases of Guillain-Barre syndrome and a mortality of 5 percent. Subsequent yearly programs with other types of vaccine are described. Dosages vary according to the age of the vaccinee. Those who need vaccination include persons over 65 years of age, patients with heart/lung, liver/lung or metabolic diseases, severe anemia, or a compromised antigenic system. Side effects include local reaction, fever, an allergic reaction (due to egg protein), and the Guillain-Barre syndrome (only with swine virus vaccine). In general, influenza vaccine is safe and confers 60 85 percent protection. Since immunity lasts only about a year, annual vaccination with recently isolated virus vaccine is recommended. Amantadine seems effective therapeutically and prophylactically for clinical influenza A infection. PMID- 6246154 TI - Update on drug therapy: II. Timolol maleate ophthalmic solution. PMID- 6246155 TI - Attitudes toward women physicians in a Mormon community. PMID- 6246156 TI - The supply of reduced-schedule residencies. PMID- 6246157 TI - Cardiovascular disease and the need for prophylaxis. PMID- 6246158 TI - Hypogeusia and hyposmia associated with low serum zinc levels, a case report. PMID- 6246159 TI - Malignant hyperthermia: a review. PMID- 6246160 TI - Update on drug therapy. IV. Parenteral cephalosporins. PMID- 6246161 TI - Effect of short dexamethasone suppression on plasma steroids in prepubertal and pubertal girls. AB - In 40 girls aged from 2 to 14 years, subdivided into groups according to age and pubertal development, and in 6 adult female volunteers, plasma cortisol (F), pregnenolone (delta 5), dehydroepiandrosterone (DHA) progesterone (P), 17 hydroxyprogesterone (17P), androstenedione (A), testosterone (T) and estradiol (E2) were measured before and after short dexamethasone (DXM) suppression. The results confirmed the capacity of DXM to inhibit plasma steroids in all age groups, except T in 2-9 year old and P1 Tanner's stage girls. The percentage suppression of each given steroid was constant over the age groups from 6-9 years to P4-5 Tanner's stage, while lower suppression was found in 17P, P and DHA in 2 5 year old girls and in 17P, DHA and E2 in adult women. These results emphasize the fundamental role of ACTH as the overall stimulating factor of adrenal steroidogenesis but do not negate the possibility of another factor responsible for the development of the adrenal androgen secreting cells throughout prepuberty and puberty. PMID- 6246162 TI - Isolated ACTH deficiency confirmed by ACTH radioimmunoassay. AB - A 28 year old woman presented with symptoms and biochemical findings suggesting hypoglycemia. Detailed endocrine investigations indicated secondary adrenocortical insufficiency with no rise in plasma ACTH or plasma cortisol following insulin-induced hypoglycemia or vasopressin infusion. The adrenal glands however produced cortisol normally following prolonged stimulation with depot tetracosactrin. Other anterior pituitary hormones were released normally following appropriate stimulation tests. The literature on isolated ACTH deficiency is briefly reviewed, and this case represents one of the few reports in which the diagnosis has been substantiated by ACTH radioimmunoassays. PMID- 6246163 TI - A comparative study of new substrates for the histochemical demonstration of acid phosphomonoesterase activity in tissues which secrete acid phosphatase. AB - The histochemical demonstration of acid phosphatase activities against phosphoethanolamine (PEA), phosphorylcholine (PC), and D-ephedrine phosphate (DEP) are reported for a variety of rat tissues and are compared to acid beta glycerophosphatase (beta GPase) activity. Intense acid beta GPase activity was demonstrated in all tissues examined. However, liver, kidney, intestine, spleen and bone marrow cells failed to exhibit any enzyme activity against PEA, PC, or DEP. In addition, significant differences in the hydrolysis of these substrates were noted among the tissues that did demonstrate activity (bone, tooth, oral mucosa, sebaceous gland, and prostate gland). These observations suggest that PEA, PC, and DEP are more specific substrates for acid phosphatase than beta GP and permit the differential localization of several distinct acid phosphatase isoenzymes. PMID- 6246164 TI - Correlated biochemical and cytochemical studies of nucleoside diphosphatase. PMID- 6246165 TI - Wholemeal bread and satiety. AB - Ten normal volunteers were offered unlimited amounts of bread, butter and jam at midday on four successive Tuesdays: on two days the bread was white (70 per cent extraction flour) and on the other two days it was wholemeal (100 per cent extraction flour). Contrary to previous reports, there was no significant effect of the type of bread on the quantity or type of nutrient intake at the meal, or in the subsequent 24 hours. PMID- 6246166 TI - Antibodies to murine leukemia virus gp70 and p15(E) in sera of BALB/c mice immunized with syngeneic chemically induced sarcomas. AB - The sera of BALB/c mice immunized with syngeneic methylcholanthrene-induced sarcomas commonly contain antibodies that react with the immunizing tumor line and also with other chemically induced sarcomas. Three lines of evidence suggest that the cross-reactive antibodies are directed against antigenic determinants of gp70 and p15(E), envelope proteins of endogenous murine leukemia virus (MuLV). 1) The antibodies bind only to sarcomas expressing MuLV antigens, 2) they are removed by absorption with purified MuLV antigens, and 3) they precipitate proteins identified as gp70 and p15(E) from 125I-labeled sarcoma cell lysates. PMID- 6246167 TI - Metabolic heterogeneity among human monocytes and its modulation by PGE2. PMID- 6246168 TI - Cell surface glycoproteins of rat lymphocytes. II. Protease-sensitive glycoproteins associated with mitogeni stimulation by periodate or neuraminidase plus galactose oxidase. PMID- 6246169 TI - Characterization of responding cells in oxidative mitogen stimulation. I. Ia+ cells and Ly-1+2+ cells are required for the proliferative response. AB - Addition of anti-Ia sera to cultures of mouse spleen cells stimulated with oxidative mitogens, neuraminidase/galactose oxidase (NaGO) or sodium periodate (NaIO4), inhibits the subsequent proliferative response 30 to 70%. Anti-H-2K or D sera were not specifically inhibitory. Similar inhibition was seen when cells were pretreated with anti-Ia sera and washed before exposure to the mitogenic enzymes. Treatment with anti-Ia serum and complement depletes greater than 89% of the NaGO and the NaIO4 responses but 2% or less of the phytohemagglutinin (PHA) response. The response to NaGO was sensitive to depletion with anti-Thy-1 serum, rabbit anti-mouse brain serum, anti-Ly-1, or anti-Ly-2 serum. Mixtures of Ly-1 and Ly-2-depleted populations did not restore responsiveness. Thus both an Ia+ cell and an Ly-1+2+ T cell are required for [3H]TdR incorporation in response to NaGO treatment. PMID- 6246170 TI - Macrophage accumulation in mice is inhibited by low molecular weight products from murine leukemia viruses. AB - Low m.w. extracts from three known oncogenic viruses, Friend, Moloney, and Rauscher, inhibited the accumulation of macrophages at sites of delayed inflammatory reactions in mice. The potential biologic significance of these proteins is suggested by their potency: as little as 1.2 ng of viral protein inhibited (p less than 0.02) macrophage accumulation when injected at a site distant to the inflammatory reaction. A virus envelope protein fraction of 15,000 daltons (p15E) was likewise found to inhibit macrophage accumulation and may in part represent the active factor of the virus extracts. Certain oncogenic viruses may thus exert their immunosuppressive activity by release of potent inhibitors of systemic macrophage function. PMID- 6246171 TI - Fetal neural antigens on human neuroblastoma cells. PMID- 6246172 TI - Purification and biochemical characterization of an inhibitor of DNA synthesis produced by an Epstein-Barr virus-transformed B cell line. AB - An inhibitory factor, which has been shown to suppress the uptake of 125I iododeoxyuridine by both lymphoid and nonlymphoid cells, was isolated from the supernatant of an Epstein-Barr virus- (EBV) transformed B cell line (1605L) established from a cotton-topped marmoset. Purification of the inhibitor, which was produced in serum-free medium by crowded cultures of the 1605L cells, was achieved by DEAE-cellulose chromatography followed by preparative polyacrylamide gel electrophoresis. The apparent m.w. of the 1605L factor was determined to be 65,000 to 70,000 by SDS-polyacrylamide gel electrophoresis. The inhibitor was sensitive to digestion by trypsin and chymotrypsin but not RNase or DNase, indicating that it was protein in nature. Exposure of the 1605L factor to 56 degrees C for 1/2 hr or pH 2 for 48 hr at 4 degrees C destroyed its inhibitory activity. The biochemical characteristics and activity of the 1605L inhibitor distinguish it from Type I interferon and several other soluble immunologic mediators known to be produced by lymphoid cell lines. PMID- 6246173 TI - Diurnal variation in cyclic nucleotide levels in normal and phorbol myristate acetate treated mouse epidermis. AB - The diurnal variations in cyclic AMP, cyclic GMP and cyclic GMP/cyclic AMP were determined in mouse epidermis. Slight (60%) diurnal fluctuations were observed in the levels of cyclic AMP and cyclic GMP/cyclic AMP while cyclic GMP showed a more substantial (250%) variation. All 3 parameters showed peaks between 10 AM and 2 PM. The tumor promoter phorbol myristate acetate had no effect on the variation in either cyclic AMP or cyclic GMP, but did appear to reduce the extent of diurnal variation in cyclic GMP/cyclic AMP ratios. The diurnal variation in epidermal mitosis in these mice showed a maximum at 2 PM and a minimum at 10 PM to 2 AM. PMID- 6246174 TI - The effects of epidermal growth factor on the cyclic nucleotide system in pig epidermis. AB - Incubation of pig skin slices with epidermal growth factor (EGF) caused an increase in intracellular cyclic GMP concentration. A significant increase was found after 1 hr of incubation and reached a peak by 6 hr. EGF caused no change in the cyclic AMP level nor did it affect epinephrine-induced cyclic AMP responses. PMID- 6246175 TI - Temporal cluster of herpes simplex encephalitis: investigation by restriction endonuclease cleavage of viral DNA. AB - Eight patients with brain biopsy-proven herpes simplex encephalitis were seen at the Massachusetts General Hospital, Boston, within a three-month period in the summer of 1977. The unusual temporal clustering of these cases engendered a formal epidemiologic investigation. No significant link among these patients was uncovered, and analysis of the cleavage products of seven of the eight viral isolates produced by the restriction endonucleases HsuI and HpaI showed that they were different. This cluster thus appears to have been a random event. Its occurrence, however, emphasizes that herpes encephalitis is not a rare disease in this country. In addition, the utility of restriction enzyme cleavage of DNA in clarifying the epidemiology of viral disease is underscored. PMID- 6246176 TI - Establishment of cytomegaloviral infection in mice: role of a macrophage-enriched subpopulation. AB - The role of a macrophage-enriched subpopulation in acute intraperitoneal infection of mice with cytomegalovirus was investigated. Virus was not detectable in extracellular fluid after the first day, but it could be isolated from peritoneal exudate cells for at least three weeks after infection. The virus was found in adherent and nonadherent cells after plastic-adherence separation. Infection of recipient mice was achieved by adoptive transfer of either subpopulation two or 21 days after infection. Further study of the macrophage enriched adherent subpopulation revealed no evidence of significant viral replication. Pretreatment of mice to activate macrophages did not impair dissemination of the virus. Thus, cytomegalovirus can infect a subpopulation of cells enriched in macrophages, and although little replication occurs, such infection facilitates the establishment of persistent infection. PMID- 6246177 TI - Cell-mediated immunity to varicella-zoster virus after allogeneic marrow transplant. AB - The cellular immune response of normal persons and marrow transplant recipients to varicella-zoster virus (VZV) antigen was measured with use of the lymphocyte transformation response. Ninety-nine of 100 normal persons with previous VZV infection had a stimulation index of greater than or equal to 4.8, while 10 susceptible persons had responses of less than or equal to 3.0. Before transplant, responses were lower than normal in patients with leukemia in relapse (P = 0.001), but not in patients with leukemia in remission or with aplastic anemia. Throughout the first 100 days after transplant, lymphocyte response was depressed (P less than 0.0005), especially among recipients of antithymocyte globulin during days 41-80 (P less than 0.05). Patients with aplastic anemia had higher responses than those with leukemia during days 20-60 (P less than 0.02). By one year, most responses were normal. Long-term survivors who had recurrent VZV infection had positive responses more often than those without recurrent infection (P = 0.01). The lymphocyte response to VZV antigen parelleled, and thus may predict, periods of increased susceptibility to VZV infection. PMID- 6246178 TI - Mechanisms of immunosuppression in cytomegaloviral mononucleosis. AB - During acute cytomegaloviral (CMV) mononucleosis, mononuclear leukocytes displayed diminished responsiveness to certain mitogens. Responses to phytohemagglutinin were normal in patients with community-acquired CMV illness but were reduced in patients with transfusion-associated infection. Both groups were hyporesponsive to pokeweek mitogen and concanavalin A. Cells from convalescent CMV mononucleosis patients responded as well as cells from normal donors to the three mitogens. Preculture of cells from patients with acute CMV mononucleosis for up to seven days before addition of concanavalin A greatly enhanced the blastogenic response to that mitogen. The effect was increased further by depletion of adherent cells after preculture for seven days and could be markedly reduced by the addition of fresh, autologous adherent cells to the precultured nonadherent cells. Suppressor activity was not observed in the serum of patients with acute CMV mononucleosis. These studies suggest that mitogen hyporesponsiveness in CMV mononucleosis may be mediated by suppressor cells included among the plastic-adherent mononuclear leukocyte population. PMID- 6246179 TI - Incubation of swab materials with herpes simplex virus. PMID- 6246180 TI - Comparative efficacy of antiherpes drugs against different strains of herpes simplex virus. AB - A large variety of antiherpes compounds was compared for their inhibitory activity against laboratory strains and clinical isolates of herpes simplex virus (HSV) type 1 and type 2. From studies performed in primary rabbit kidney cell cultures, six, E-5-(2-bromovinyl)-2'-deoxyuridine, E-5-(2-iodovinyl)-2' deoxyuridine, 5-vinyl-2'-deoxyuridine, 2'-fluoro-5-iodoaracytosine, acycloguanosine, and 5-iodo-2'-deoxycytidine, emerged as the most potent and selective antiherpes agents. For HSV type 1, the 50% inhibitory doses (ID50) were 0.008, 0.012, 0.018, 0.017, 0.04, and 0.06 micrograms/ml, respectively; those for HSV type 2 were 1, 2, 0.1, 0.05, 0.04, and 0.3 microgram/ml, respectively. These compounds did not inhibit host-cell metabolism or replication of vaccinia virus except at concentrations 100--10,000 times greater than the ID50 for any HSV. All were significantly less inhibitory for a thymidine kinase (TK)-deficient mutant of HSV type 1 than for normal strains, suggesting that phosphorylation by virus induced TK was required to produce specific inhibition of HSV replication. PMID- 6246181 TI - Molecular analysis of R-factors from multiresistant nosocomial isolates. AB - During an epidemic of infections at the Seattle Veterans Hospital, Washington, due to a multiresistant strain of Serratia marcencens, other enteric species were isolated that had antibiograms nearly identical to those of the epidemic S. marcescens. In 11 instances, these multiresistant species were isolated from specimens that also contained the epidemic serratia strain. All isolates of the epidemic serratia strain contained a conjugative 45-megadalton R-factor (pLST1000) coding for intermediate resistance to three amino-glycosides (minimal inhibitory concentrations, 4--8 micrograms/ml) and high-level resistance to ampicillin, carbenicillin, cephalothin, streptomycin, and sulfonamide. With the use of agarose gel electrophoresis and restriction endonuclease cleavage patterns after digestion with EcoRI, BamH1, and HindIII, it was determined that eight different enteric strains of six different species isolated from the patients contained an R-factor that was molecularly identical to the one isolated from the epidemic strain of S. marcescens. Thus, the epidemic of multiresistant infections at this hospital was caused both by the spread of an epidemic strain and an "epidemic plasmid." The molecular characteristics of pLST1000 appear to be different from previously described multiresistant plasmids. PMID- 6246182 TI - Control of endogenous triglyceride breakdown in the mouse diaphragm. AB - The control of endogenous triglyceride breakdown was studied in vitro, in the incubated intact mouse diaphragm. Isoproterenol (2 microgram/ml) produced parallel increases in glycerol and free fatty acid release, and in tissue cyclic AMP levels, suggesting that cyclic AMP mediates the action of the catecholamine on triglyceride mobilization. In addition to cyclic AMP, calcium seems to be involved in the action of isoproterenol because preincubation of hemidiaphragms in the presence of the calcium ionophore A23187 decreased the lipolytic effect of the drug. Insulin (12.5 mU/ml) antagonized the action of isoproterenol on triglyceride breakdown (it decreased glycerol and free fatty acid release) without altering its stimulatory effect on cyclic AMP levels. On the other hand, no detectable effect on lipolysis was observed with carbachol in control and denervated hemidiaphragms, although the latter possess acetylcholine receptors over the entire surface area of the muscle. It was concluded that catecholamines control triglyceride breakdown in muscle while the cholinergic system does not seem to be involved. Cyclic AMP, calcium, and insulin all affect lipolysis in muscle and the interrelationships remain to be elucidated. PMID- 6246183 TI - Lipolysis and cyclic AMP response to isoproterenol in diaphragms from control and dystrophic mice. AB - A comparison was made of the sensitivity of lipolysis (glycerol and free fatty acid release) and of cyclic AMP production to the action of isoproterenol in diaphragms from control and dystrophic Bar Harbor mice at 7 weeks of age. An increased lipolytic response was observed in diaphragms from dystrophic mice that was more apparent in the males, and was demonstrable when cyclic AMP was used instead of isoproterenol. The increased glycerol and free fatty acid release in response to isoproterenol and cyclic AMP cannot be explained by a higher triglyceride content of diaphragms from dystrophic mice, because it was found to be similar to that of controls when it was estimated by biochemical and light microscopic techniques. The increased lipolytic response was not paralleled by changes in cyclic AMP levels, which were found to be similar in diaphragms from control and dystrophic mice, whether in the basal or the stimulated state. It was concluded that the lipolytic apparatus in muscles from dystrophic mice shows an increased sensitivity to isoproterenol that seems to be related to events more intracellular than the cAMP production step. PMID- 6246184 TI - Studies on drug-induced lipidosis: subcellular localization of phospholipid and cholesterol in the liver of rats treated with chloroquine or 4,4'-bis (diethylaminoethoxy)alpha, beta-diethyldiphenylethane. AB - Administration of chloroquine or 4,4'-bis(diethylaminoethoxy)alpha, beta diethyldiphenylethane (DH) to rats in oral doses of 100 mg/kg for 7 days causes phospholipid and cholesteryl ester accumulation in liver. To further characterize this drug-induced lipidosis, we have isolated and characterized the lipids of subcellular fractions from control rats and rats treated with chloroquine, DH, and Triton WR-1339. The phospholipid content of liver is increased 1.5-fold by chloroquine or DH treatment but is unaffected by Triton WR-1339. Acid phosphatase is increased by treatment with these three agents. Chloroquine and DH cause a shift of acid phosphatase from the light mitochondrial fraction (L) to the heavy mitochondrial fraction (M). Multilamellar bodies, an ultrastructural hallmark of chloroquine and DH-induced lipidosis, were isolated in a highly-purified form from the M fraction of chloroquine- or DH-treated rats. They are highly enriched in acid phosphatase indicating their lysosomal origin. In addition, they contain large amounts of phospholipid, cholesterol, and cholesteryl ester and are the sole site of bis(monoacylglycero)phosphate and the enzyme which catalyzes its synthesis from phosphatidylglycerol. Analysis of the phospholipid content of the respective control and drug-treated liver fractions shows that the entire excess phospholipid content of chloroquine- or DH-treated liver can be accounted for by the drug-induced multilamellar bodies. Triton WR-1339-induced lysosomes, which were isolated for comparison, also contain bis(monoacyglycero)phosphate and bis(monoacyglycero)phosphate synthetase. However, they differ from the drug induced lysosomes in that their sphingomyelin content is much higher and their total phospholipid and phosphatidylinositol content much lower. The multilamellar bodies are the principal intracellular site of accumulation of chloroquine and DH, respectively. Increased delivery of phospholipid to lysosomes and decreased lysosomal catabolism of phospholipid are the factors which are thought to cause this experimental lipidosis. High levels of phosphatidylinositol in the multilamellar body may be in part responsible for the increased content of bis(monoacyglycero)phosphate since it has been identified as an acyl donor in bis(monoacylglycero)phosphate synthesis. PMID- 6246185 TI - Activation of adenosine 3',5'-monophosphate-dependent protein kinase and its relationship to cyclic AMP and lipolysis in hamster adipose tissue. AB - The interrelationships among cAMP-dependent protein kinase activity, lipolysis, and cellular concentrations of cAMP were investigated in hamster epididymal adipose tissue. Isoproterenol, norepinephrine, and theophylline increased the protein kinase activity assayed in tissue extracts with no added cAMP, but not in the presence of added cyclic nucleotide. The maximum rate of lipolysis was associated with a nearly three-fold increase in cAMP levels and a protein kinase activity ratio of 0.8 (the ratio of activity assayed without cAMP to that assayed with cAMP). Rates of lipolysis less than maximum were associated with lesser degrees of protein kinase activity and lower levels of cAMP. The relatively pure alpha-adrenergic agent phenylephrine partially suppressed the isoproterenol stimulated protein kinase activity, lipolysis, and cAMP levels. Conversely, the alpha-adrenergic blocking agent phentolamine increased the activity of protein kinase and cAMP levels in adipose tissues exposed to norepinephrine. These data are consistent with the primary role for cAMP and its dependent protein kinase in control of lipolysis in adipose tissue. Moreover, our data are consistent with the view that the antilipolytic action of alpha-adrenergic agents is mediated by a decrease in activity of protein kinase, caused by a decrease in cellular cAMP concentrations. PMID- 6246186 TI - Trophoblastic disease in Alabama. PMID- 6246187 TI - Synaptic relationships of the cerebral giant cells with motoneurones in the feeding system of Lymnaea stagnalis. AB - 1. The cerebral giant cells (CGCs) of Lymnaea have a tonic, modulatory effect on the intensity of output from feeding motoneurones in the buccal ganglia. 2. Short latency, excitatory and probably monosynaptic connexions occur between the CGCs and three identified feeding motoneurones. Unitary excitatory postsynaptic potentials in these motoneurones, following CGC spikes, are of different sizes and durations, and hence have different summation properties. 3. The CGCs make long latency, excitatory polysynaptic connexions with four other feeding motoneurone types. 4. Bursts of spikes in the CGCs, resulting from phasic synaptic input, synchronous with the feeding cycle, amplify their modulatory effect on burst intensity in feeding motoneurones. 5. Thte for reinforcing their cyclic burst activity. PMID- 6246188 TI - Amplified env and gag products on AKR cells. Origin from different murine leukemia virus genomes. AB - Thymocytes of AKR mice express two species of gp70, the envelope glycoprotein of murine leukemia virus (MuLV), encoded by the env gene. One is denoted Ec+ gp70 in reference to the type-antigen Ec and association with ecotropic virus. The other, Ec- gp70, resembles gp70 found also on thymocytes of mouse strains that are not overt producers of MuLV, and has no evident relation to ecotropic virus. Expression of Ec- gp70 type, but not of Ec+ gp70 type, is amplified with age on AKR thymocytes. In contrast, viral core polyproteins, encoded by the gag gene and simultaneously amplified with age, appear to be related to ecotropic virus. These observations imply selective amplification of products of env and gag genes from two sorts of provirus, a phenomenon which may be connected to the dual genetic origin of recombinant mink-cell-focus inducing viruses in AKR mice. PMID- 6246189 TI - Influence of Fv-1 alleles on cellular expression of gp70. AB - Type-variants of gp70 (glycoprotein-70), which is the major envelope protein of C type mouse virus and is also found in plasma membranes, are identified immunogenetically by the antigens Gix and Ec. Cellular expression of Gix+ gp70 does not depend on production of virus, but expression of Ec+ gp70 (formerly X gp70) has been observed only in AKR and other strains of mice that produce large amounts of virus throughout life. To test the inference that cellular expression of Ec+ gp70 is secondary to production of virus we examined the effect of Fv-1 alleles, which govern the replicability of N-tropic and B-tropic C-type virus, on the expression of Ec+ gp70 on thymocytes. By typing thymocytes of Fv-1-congenic mice for Ec+ gp70 was found that manifestation of the Ec+ gp70 phenotype requires the Fv-1n allele, which is permissive for replication of N-tropic virus produced by AKR and other virus-producing mouse strains. Substitution of the Fv-1b allele for the Fv-1n allele abolishes demonstrable expression of Ec+ gp70 by AKR thymocytes at ages up to 9 mo, the oldest AKR mice tested. PMID- 6246190 TI - Evidence suggesting a role for cyclic nucleotides in acrosome reactions of hamster sperm in vitro. AB - There have been conflicting reports concerning the involvement of cyclic nucleotides in sperm capacitation. We have examined the effects of micromolar concentrations of dibutyryl cyclic AMP (Bt2cAMP) and of the phosphodiesterase inhibitors SQ20009 and ICI63,197 on hamster sperm incubated under in vitro capacitating conditions. Washed hamster sperm were incubated in a capacitation media containing bovine serum albumin, and a protein-free "motility-factor" from bovine adrenal cortex. Incubation for 3.5 hours was followed by addition of one of the compounds (0.1-10 microM) or control buffer. At the time of addition and after 30-120 minutes further incubation, sperm were examined by phase contrast microscopy. The final motility was similar to the initial motility (50-70%) and the same in incubation of controls or experimental compounds. Bt2cAMP, SQ20009, and ICI63,197 at these concentrations stimulated acrosome reactions to a statistically significant extent (P less than 0.005) compared to controls. Activation was stimulated to a varying degree by all three experimental compounds. These results suggest a role for cyclic nucleotides in capacitation and the acrosome reaction of hamster sperm. PMID- 6246191 TI - Neurons, potassium, and glia in proximal retina of Necturus. AB - Light-evoked K+ flux and intracellular Muller (glial) cell and on/off-neuron responses were recorded from the proximal retina of Necturus in eyecups from which the vitreous was not drained. On/off-responses, probably arising from amacrine cells, showed an initial transient and a sustained component that always exhibited surround antagonism. Muller cell responses were small but otherwise similar to those recorded in eyecups drained of vitreous. The proximal K+ increase and Muller cell responses had identical decay times, and on some occasions the latency and rise time of the K+ increase nearly matched Muller cell responses, indicating that the recorded K+ responses were not always appreciably degraded by electrode "dead space." The spatiotemporal distribution of the K+ increase showed that both diffusion and active reuptake play important roles in K+ clearance. The relationship between on/off-neuron responses and the K+ increase was modelled by assuming that (a) K+ release is positively related to the instantaneous amplitude of the neural response, and (b) K+ accumulating in extracellular space is cleared via mechanisms with approximately exponential time courses. These two processes were approximated by low-pass filtering the on/off neuron responses, resulting in modelled responses that match the wave form and time-course of the K+ increase and behave quantitatively like the K+ increase to changes in stimulus intensity and diameter. Thus, on/off-neurons are probably a primary source of the proximal light-evoked K+ increase that depolarizes glial cells to generate the M-wave. PMID- 6246193 TI - Streptomyces albus G mutants defective in the SalGI restriction-modification system. AB - Streptomyces albus G mutants (at least 12 of which were independent) defective in SalGI-mediated restriction (R-) were isolated after mutagenesis. Some of them lacked detectable SalGI activity in cell-free extracts. Some were also partially or completely defective in SalFI-associated modification (M-). Loss of restriction rendered S. albus G sensitive to many phages to which it was normally totally resistant. DNA from one such phage had many SalGI target sites (mean, one site per 1.35 kilobases). A mutant was isolated which was heat-sensitive for growth, apparently because it was restriction-proficient but temperature sensitive for modification. At a rather high frequency, this mutant generated spontaneous heat-tolerant derivatives which were nearly all R-. Such R- mutants were always M- rather than being temperature-sensitive for modification. In a limited genetic analysis, the determinants of restriction and modification did not recombine with each other, and since there was no reassortment of these phenotypes among the parental output of crosses it appeared that the determinants were located close together on the chromosome. PMID- 6246192 TI - A covalently bound photoisomerizable agonist: comparison with reversibly bound agonists at Electrophorus electroplaques. AB - After disulphide bonds are reduced with dithiothreitol, trans-3- (alpha bromomethyl)-3'-[alpha- (trimethylammonium)methyl]azobenzene (trans-QBr) alkylates a sulfhydryl group on receptors. The membrane conductance induced by this "tethered agonist" shares many properties with that induced by reversible agonists. Equilibrium conductance increases as the membrane potential is made more negative; the voltage sensitivity resembles that seen with 50 [mu]M carbachol. Voltage- jump relaxations follow an exponential time-course; the rate constants are about twice as large as those seen with 50 muM carbachol and have the same voltage and temperature sensitivity. With reversible agonists, the rate of channel opening increases with the frequency of agonist-receptor collisions: with tethered trans-Qbr, this rate depends only on intramolecular events. In comparison to the conductance induced by reversible agonists, the QBr-induced conductance is at least 10-fold less sensitive to competitive blockade by tubocurarine and roughly as sensitive to "open-channel blockade" bu QX-222. Light flash experiments with tethered QBr resemble those with the reversible photoisomerizable agonist, 3,3',bis-[alpha-(trimethylammonium)methyl]azobenzene (Bis-Q): the conductance is increased by cis {arrow} trans photoisomerizations and decreased by trans {arrow} cis photoisomerizations. As with Bis-Q, ligh-flash relaxations have the same rate constant as voltage-jump relaxations. Receptors with tethered trans isomer. By comparing the agonist-induced conductance with the cis/tans ratio, we conclude that each channel's activation is determined by the configuration of a single tethered QBr molecule. The QBr-induced conductance shows slow decreases (time constant, several hundred milliseconds), which can be partially reversed by flashes. The similarities suggest that the same rate limiting step governs the opening and closing of channels for both reversible and tethered agonists. Therefore, this step is probably not the initial encounter between agonist and receptor molecules. PMID- 6246194 TI - Effects of oligomycin on glucose utilization and calcium transport in African trypanosomes. AB - Oligomycin (3 microgram ml-1) inhibited glucose utilization in Trypanosoma brucei S42 as shown by measurements of oxygen uptake and pyruvate production. Carbonyl cyanide 3-chlorophenylhydrazone, an uncoupler of oxidative phosphorylation, did not relieve this inhibition, although some relief was afforded by the alternative substrate glycerol. Naturally dyskinetoplastic Trypanosoma evansi MIAG 105 was less sensitive to inhibition by oligomycin although glycerol relief was still observed, relecting the differential sensitivity of the two pathways. With glucose present as the substrate, 45Ca2+ transport was inhibited by oligomycin in T. brucei, but was stimulated in T. evansi. These results are discussed in terms of alternative systems for maintaining cytoplasmic Ca2+ concentrations in normal and dyskinetoplastic strains of trypanosome. PMID- 6246195 TI - Tubular structures in the cervix of mice experimentally infected with herpes simplex virus type 2. AB - Experimental infection of the C3H/N mouse genital tract was demonstrated after intravaginal inoculation with herpes simplex virus type 2 (HSV-2). About 75% of the infected animals died by Day 7, and 75% of the surviving animals had severe vaginitis or neurological signs on Day 7. Titers of the virus recovered from vaginal secretions of infected animals reached a maximum on Day 2 and gradually decreased until Day 7. On the other hand, under the electron microscope, virus particles and tubular structures could be found in the nuclei of infected cells of the cervix in the 1st, 2nd and 4th days after infection. All cases in which virus particles could be found in the nuclei of infected cells were also positive for tubular structures and vice versa. These observations indicate that in situ diagnosis of HSV-2 infection can be made in the mouse model. The same method would be applicable for the diagnosis of human HSV-2 infection. PMID- 6246196 TI - Antiviral activity of colostrum and serum immunoglobulins A and G. AB - Enteric virus-specific IgA and IgG present in paired human sera and colostrums were measured by the enzyme-linked immunosorbent assay (ELISA). Virus-specific IgA was present in all colostrums, but virus-specific IgG could not be detected. The reverse was true when sera were assayed. Most of these colostrums also neutralized either polio virus or reovirus, as did IgA, which was separated from a pool of colostrums by exclusion chromatography. No correlation could be made between levels of neutralizing and ELISA antibody titers in colostrums. PMID- 6246197 TI - Rotavirus and other viruses in the stool of premature babies. AB - In a 12-month study, 363 stools of 199 premature babies nursed in a separate ward of a paediatric clinic were examined by electron microscopy and on cell culture to detect virus. Twenty-four (6.6%) were positive for rotavirus, in one winter epidemy. From four stools Echo 22 was isolated, and in six cases virus-like particles were detected by electron microscopy. These virus infections are not a major problem in newborns, requiring special care, as they are mostly symptomless or mild. PMID- 6246198 TI - An outbreak of hepatitis A in an institution for the mentally retarded. AB - From December 1977 until April 1978 a hepatitis A outbreak occurred in an institution for the mentally retarded. The institution housed 311 residents and had a staff of 308. The outbreak was studied by enzyme-linked immunosorbent assays for hepatitis A antigen and antibodies, and by liver function tests in serum. When the investigations started, 13 residents and one staff member were ill and already seropositive; 34 of the 182 residents that were seronegative at that time and 12 of the 223 seronegative staff members subsequently developed disease. Out of the 60 cases 32 were asymptomatic; 19 cases with jaundice were seen. Normal human immunoglobulin was administered to a large part of the seronegative group, but the effect is difficult to interpret as the immunoglobulin was often given after the presumed time of infection and failed to protect. Elevated liver enzyme levels were demonstrated in 38 of 60 patients. PMID- 6246199 TI - Depolarisation-induced release of ATP from cortical synaptosomes is not associated with acetylcholine release. PMID- 6246200 TI - Changes in the uptake of GABA and taurine during neuronal and glial maturation. PMID- 6246201 TI - The effects of electroshock convulsions on calcium transport within synaptic terminals. PMID- 6246202 TI - The effect of acute hypoxia on synaptosomes from rat brain. PMID- 6246203 TI - Morphological and biochemical changes in the cerebellum induced by kainic acid in vivo. PMID- 6246204 TI - Biochemical characterization of myelin isolated from the central nervous system of Xenopus tadpoles. PMID- 6246205 TI - Partial purification of nuclear protein kinase from small dense nuclei of mouse brain and the effect of chronic morphine treatment. PMID- 6246206 TI - Temperature dependence of muscarinic acetylcholine receptor activation, desensitization, and resensitization. PMID- 6246207 TI - Mechanisms of cyclic AMP regulation in cerebral anoxia and their relationship to glycogenolysis. PMID- 6246208 TI - Depolarization-evoked accumulation of cyclic AMP in brain slices: the requisite intermediate adenosine is not derived from hydrolysis of released ATP. PMID- 6246210 TI - Increased motor unit fibre density in the external anal sphincter muscle in ano rectal incontinence: a single fibre EMG study. AB - The motor unit fibre density in the external anal sphincter muscle has been measured in 13 normal subjects aged 18 to 78 years, and in 14 patients with ano rectal incontinence, aged 17 to 72 years. The mean fibre density in the normal subjects was 1.5 +/- 0.16, and in the incontinent subjects it was 2.17 +/- 0.28 (p less than 0.001). These findings provide support for the suggestion that ano rectal incontinence commonly has a neurogenic basis. PMID- 6246209 TI - Successuful treatment of paramyotonia congenita (Eulenburg): muscle stiffness and weakness prevented by tocainide. AB - Recent studies have shown that the sodium conductance of the sarcolemma is disturbed in paramyotonia. Tocainide is a new antiarrhythmic agent which seems to reduce effectively sodium conductance. Eight patients with paramyotonia were treated with tocainide, whereby the paramyotonic stiffness and weakness brought about by cooling could be prevented. PMID- 6246211 TI - Stimulation of active E-rosette forming lymphocytes from multiple sclerosis patients by gangliosides and cerebrosides. AB - An active subpopulation of blood T-lymphocytes, characterized by rapid (4 min) rosette formation with sheep erythrocytes was measured in multiple sclerosis (MS) patients, other neurological diseases (OND) and healthy subjects after 15 min incubation with low doses (0.1-5 pg) of brain cerebrosides and gangliosides. A 15% rise in the active E-rosettes after incubation with antigens was indicative of a response to given antigen. Peripheral blood lymphocytes from all 35 patients with MS responded to brain cerebrosides in the active E-rosette test (AER). Lymphocytes from 33 MS patients also responded to brain gangliosides. Three out of 26 other neurological patients were stimulated by cerebrosides and gangliosides. Fifteen healthy subjects did not respond to any antigen in the AER test. The significance of the results in relation to the process of demyelination is discussed. PMID- 6246212 TI - Antigen-induced suppression of experimental allergic neuritis in the guinea pig. AB - Treatment of guinea pigs suffering from a fatal form of experimental allergic neuritis (EAN) using P2 basic protein of PNS myelin reduced the clinical severity, the overall mortality and the incidence of respiratory problems. The large basic protein (MBP) common to the CNS and PNS had no suppressive effect on EAN. Cyanogen bromide cleavage of P2 destroyed its suppressive activity. P0 protein of PNS myelin had marginal suppressive activity but Cop 1, a synthetic copolymer effective in suppressing EAE, was without significant effect on EAN. The suppression with P2 protein of a milder form of EAN (induced with a reduced amount of PNS myelin) was less marked. Increasing the treatment period from 10 to 15 days did not increase the suppressive effect of P2 in the milder form of EAN. PMID- 6246213 TI - Pathogenesis of human poliovirus infection in mice. I. Clinical and pathological studies. AB - Human poliovirus infection in mice was studied to determine the similarities to human poliomyelitis, the selective vulnerability of neurons to infection, the role of the immune response in age-dependent susceptibility, and possible viral persistence. Mice inoculated intracerebrally (ic) with the Lansing type 2 poliovirus developed a disease with clinical, pathological, and age-dependent features resembling human poliomyelitis. Adult mice had a shorter incubation period (50% paralysis, Day 8 vs. Day 13) and a higher incidence of paralysis (97% vs. 79%) than newborns. Only paralyzed animals had pathologic changes in the spinal cord, and these corresponded to the degree of paralysis. Fluorescent antibody staining showed that selective infection of neurons was most intense in the anterior horn motor neurons of the spinal cord. There was no extraneural virus replication and no systemic neutralizing antibody response. Cyclophosphamide immunosuppression enhanced rather than diminished disease, indicating that maturation of immune responses did not explain the relative resistance of newborns to paralysis. PMID- 6246214 TI - Pathogenesis of human poliovirus infection in mice. II. Age-dependency of paralysis. AB - The mechanism of resistance of newborn mice to poliovirus-induced paralysis was studied by comparing regional virus replication in the adult and in the newborn central nervous systems (CNS) after intracerebral (ic) and intraspinal inoculation. Initial virus replication in the brains was similar in both age groups. Paralysis correlated with replication of virus in the spinal cord to a constant threshold, and this replication in newborns was delayed. Intraspinal inoculation of newborns eliminated the delay, indicating that neonatal anterior horn motor neurons were fully susceptible to infection. Cordectomy prevented the spread of virus, despite patent cerebrospinal fluid (CSF) pathways. Thus, poliovirus appeared to spread within the CNS via an axonal transport system. Known maturational changes in the fast transport system may explain the relative resistance of immature mice to poliovirus-induced paralysis. PMID- 6246215 TI - Spontaneous pallido-nigral accumulation of iron pigment and spheroid-like structures in macaque monkeys. AB - Common incidental pathologic findings in Old World monkeys are spheroid-like structures and iron pigment in the substantia nigra and globus pallidus. The occurrence of each finding correlates with the number of years monkeys have spent in captivity. The spheroids are eosinophilic and argyrophilic, but are generally PAS, iron, and luxol fast blue negative. Ultrastructurally, they consist of aggregations of dense globules and granules interspersed with membranes; normal organelles are absent. One classic spheroid with a thin myelin sheath and accumulated fibrillar material was observed. The material in spheroids is ultrastructurally distinguishable from iron pigment, which is present in glial cells, and from neuronal lipofuscin. Accumulation of spheroids and iron pigmentation may be age-related phenomena involving portions of the brain with shared anatomical and biochemical characteristics. The study of these changes may shed light on the pathogenesis of such spheroid degenerations as Hallervorden Spatz disease. PMID- 6246216 TI - Motor controls of opaline secretion in Aplysia californica. AB - 1. Using combined morphological and electrophysiological techniques, we have identified motor neurons in the right pleural ganglion of Aplysia californica that contribute to the release of opaline from the opaline gland. 2. Three pleural ganglion neurons were found to meet the requirements for identification as opaline gland motor neurons by a) sending processes in nerve P5, which innervates the gland; b) producing contractions of the gland in the absence of central synaptic activity; and c) producing excitatory junctional potentials (EJPs) in cells making up the opaline gland itself. The neurons can be reliably located and have been designated PLR1, PLR2, and PLR3. 3. When gland contraction is measured by the change in luminal pressure, the gland response is a graded function of low-frequency spike activity in the motor neurons. 4. Presumptive EJPs recorded from opaline gland cells are reversibly decreased in size by high extracellular Mg2+ and reversibly increased in size by raising the concentration of extracellular Ca2+. These results suggest that the presumptive EJPs are chemically mediated. The presumptive EJPs show facilitation and posttetanic potentiation. 5. The identified opaline motor neurons may constitute a significant portion of the motor input to the opaline gland via nerve P5 since hyperpolarization of the cells prevents the opaline gland response elicited by right connective stimulation in vitro. 6. We have compared the properties of the opaline motor neurons with the previously identified properties of the ink motor neurons (6--9, 19). Like the ink motor neurons, the opaline motor neurons have high resting potentials, are electrically coupled, and have no spontaneous spike activity. They also receive a slow and long-lasting evoked depolarizing synaptic input, which appears to be mediated by a decreased conductance mechanism. The firing pattern of the opaline motor neurons produced by synaptic input shows the same delayed bursting pattern previously described for the ink motor neurons. 7. The biophysical properties and synaptic input to the ink motor neurons have been shown to affect the features of inking behavior (4, 6--9, 19). The opaline motor neurons share some of these biophysical characteristics and mediate a defensive behavior similar to ink release. Further comparisons of these behaviors and their underlying neural circuits may provide a better understanding of the extent to which cellular biophysical properties and patterns of synaptic input influence the features of the behaviors that individual neurons mediate. PMID- 6246217 TI - Analysis of ionic conductance mechanisms in motor cells mediating inking behavior in Aplysia californica. AB - 1. The release of ink in response to a noxious stimulus is a relatively stereotyped behavior produced by strong and long-lasting stimuli. The purpose of this series of papers is to determine the quantitative extent to which the known voltage- and time-dependent ionic conductance mechanisms and synaptic influences can account for the ink gland motor neurons' firing pattern and, thus, the features of the behavior. 2. Four voltage- and time-dependent ionic currents have been analyzed. These include a fast transiet Na+-mediated inward current, a slower Ca2+-mediated inward current, a fast transient K+-mediated outward current, and a slower delayed outward current also mediated by K+ ions. 3. The current-voltage (I-V) relationships, equilibrium potentials, and steady-state activation and inactivation characteristics appear qualitatively similar to comparable currents observed in other gastropod neurons. 4. The recovery from inactivation of the delayed outward current has two time constants, one comparable to the inactivation time constant and the other more than an order of magnitude larger. The fast transient K+ current also appears to have a similar slow recovery from inactivation. 5. The synaptic current contributing to the firing pattern of the ink motor cells is a complex function of time. Initially, the synaptic conductance is high and the equilibrium potential near 0 mV. But, with time there is a gradual decrease in synaptic conductance and shift in the equilibrium potential to more depolarized levels. PMID- 6246218 TI - Quantitative aspects of ionic conductance mechanisms contributing to firing pattern of motor cells mediating inking behavior in Aplysia californica. PMID- 6246219 TI - Action-potential broadening and endogenously sustained bursting are substrates of command ability in a feeding neuron of Pleurobranchaea. AB - 1. The ventral white cells (VWC's) of the buccal ganglion of Pleurobranchaea, so named for their position and color, are a bilateral pair of neuron somata. Each sends a single axon out its contralateral stomatogastric nerve and has a dendritic field originating close to the soma. 2. The vwcs exhibit spontaneous episodes of prolonged depolarization (duration 1--4 min) accompanied by repetitive action-potential activity and separated by regular intervals of 3--30 min. Such prolonged burst episodes can be triggered by short pulses of depolarizing current. During the repetitive activity of the spontaneous bursts or that driven by imposed depolarization, the action potentials progressively broaden to 5--16 times their initial duration. 3. During spontaneous bursting or activity driven by imposed depolarization, the cyclic motor output of the feeding network is initiated or accelerated with a latency corresponding with the development of appreciable VWC spike broadening. When broadening of antidromic VWC spikes is suppressed by imposed hyperpolarization of the soma, the frequency of feeding cycles is significantly lower than when broadened spikes are allowed to develop. When trains of spikes are driven by depolarizing current, the motor output of the feeding network is not initiated until the VWC spikes have broadened to a repeatable "threshold" duration, regardless of the intensity of the depolarizing current. 4. The endogenous production of prolonged burst episodes, triggered by depolarizing current pulses, and progressive spike broadening can be demonstrated in the surgically isolated VWC soma. 5. The paired VWCs are strongly electrically coupled and display highly synchronous activity. They receive synaptic inputs from many previously identified interneurons of the feeding network and are thus reciprocally coupled within the network. 6. These results demonstrate that the capacity of this neuron to generate broadened action potentials during repetitive activity confers the ability to command coordinated motor-network output. The appropriate repetitive activity can be produced endogenously in the form of prolonged bursts of spikes. PMID- 6246220 TI - Synaptic organization of cat accessory abducens nucleus. PMID- 6246221 TI - Role of a persistent inward current in motoneuron bursting during spinal seizures. PMID- 6246222 TI - Current source-density analysis of the b-wave of frog retina. PMID- 6246223 TI - Noradrenalin, serotonin, and the dorsal horn. AB - There is anatomical, pharmacological, and physiological evidence that descending systems from the brain stem using noradrenalin and serotonin (5 hydroxytryptamine, 5-HT) participate in the control of segmental sensory processing. Study of these systems is described in this paper. L-dopa was given intravenously to cats to cause the release of noradrenalin and 5-HT. The resultant effects on the responses of dorsal horn cells to innocuous and noxious thermal stimulation of skin were determined. Using the catecholamine cell neurotoxin, 6-hydroxydopamine, the dopamine beta-hydroxylase inhibitor, fusaric acid, and the tryptophan hydroxylase inhibitor, parachlorophenylalanine, the available central stores of noradrenalin or 5-HT were altered, thus allowing separation of the effects of noradrenalin and 5-HT release on dorsal horn cells. The results indicate that noradrenalin facilitates the responses of dorsal horn cells to innocuous cutaneous stimuli, and has an inhibitory effect on the responses to noxious stimuli. Serotonin inhibits the responses of dorsal horn cells that respond to noxious stimuli, to both innocuous and noxious stimuli. The results are discussed in light of current developments concerning aminergic control of segmental sensory processing. PMID- 6246224 TI - A study of irradiated bone. III. Scintigraphic and radiographic detection of radiation-induced osteosarcomas. AB - Within 1 yr after localized irradiation of a hind limb with single (1756 rads) or fractionated (4650 rads in 3 wk) x-ray doses, radiation-induced osteosarcomas were observed in four of nine single-dose rabbits and two of 11 fractionated-dose rabbits. Tumors were observed in the proximal tibia in five cases and the distal femur in one case. In terms of production of osteoid or osseous tissue, three tumors were well differentiated, one slightly differentiated, and two (spindle cell tumors) undifferentiated. This report summarizes the Tc-99m pyrophosphate (TcPPi) imaging and autoradiographic, radiographic, and histologic studies of these osteosarcomas. The four differentiated osteosarcomas were detected 1--2.5 mo earlier by TcPPi imaging than by radiography, whereas the two undifferentiated tumors were suspected 2 wk or 3.5 mo earlier radiographically. Autoradiograms showed TcPPi localization in bone produced by differentiated osteosarcomas, and in regions of reactive bone resorption and formation peripheral to tumors. The results support a recommendation for combined radiographic and scintigraphic techniques for the early detection of osteosarcomas. PMID- 6246225 TI - Bone kinetics of calcium-45 and pyrophosphate labeled with technetium-96: an autoradiographic evaluation. AB - The uptake of calcium-45 and of pyrophosphate labeled with the long-lived technetium-96 isotope were compared by means of liquid-emulsion microautoradiograms of the epiphyseal plates of 10-week-old rabbits, at 30 min, and 3 and 48 hr after i.v. administration. For both tracers, thin sections confirm the significant role of the blood supply, especially shortly after injection. However, other more specific mechanisms lead to a mixing of the calcium in the mineral mass and to a linear deposition of technetium facing the osteoid surfaces. These findings suggest that the tropism of tin-reduced technetium pyrophosphate is not governed by the mineral pool but rather by exchanges inside a still poorly calcified organic matrix. PMID- 6246226 TI - Renal cortical imaging and the detection of renal mass lesions. PMID- 6246227 TI - Dietary control of circadian variations in serum insulin, glucagon and hepatic cyclic AMP. AB - The effect of a high-protein diet (favoring hepatic glucose production) and of a high-carbohydrate diet (favoring glucose utilization) on the concentration of insulin and glucagon in the blood and on adenosine 3',5'-cyclic monophosphate (cyclic AMP) in the liver was investigated during a 24-hour cycle in rats. Feeding a high-protein diet resulted within 3 hours in an increase in the concentration of insulin (+100%) and glucagon (+220%). Whereas feeding a high carbohydrate diet again induced a rise in insulin (+140%), no alterations in glucagon were observed. Hepatic cyclic AMP oscillated up or down under the protein or carbohydrate diet, respectively. A correlation between the insulin/glucagon molar ratio and the concentration of hepatic cyclic AMP was found. Protein-bound cyclic AMP, an indicator of protein kinase activation, corresponded closely to total cyclic AMP tissue concentration. The activity of a gluconeogenic key enzyme, P-enolpyruvate carboxykinase oscillated in parallel to hepatic cyclic AMP. Our data demonstrate that the protein and carbohydrate content of the diet determines the shape of circadian variation of hepatic cyclic AMP, insulin and glucagon. PMID- 6246228 TI - Vitamin D resistant rickets. A review and case report of an adolescent boy with a history of dental problems. PMID- 6246229 TI - Metastatic breast adenocarcinoma of the mandibular condyle: report of case. PMID- 6246230 TI - Familial occurrence of the aniridia-Wilms tumor syndrome with deletion 11p13 14.1. AB - A report of a family with two half-brothers and a maternal aunt affected with the aniridia-Wilms tumor syndrome is presented. The proband showed a deletion of most of band 11p13 and of subband 11p14.1 of one chromosome 11, and the proband's mother and an older brother, both phenotypically normal, showed a balanced chromosomal rearrangement. This family demonstrates that deletion of a small chromosome segment (11p13-14.1) is responsible for the aniridia-Wilms tumor syndrome and, that in some cases, the syndrome can be familial. PMID- 6246231 TI - Birth defects and cancer due to small chromosomal deletions. PMID- 6246232 TI - Masculinization of a female fetus by Krukenberg tumor during pregnancy. AB - A case of fetal masculinization resulting from a Krukenberg tumor in a pregnant woman is reported in a newborn infant with a sexual ambiguity of the external genitals, of the feminine pseudohermaphrodite type. She also had an incarceration of both ovaries and tubes in a right inguinoscrotal hernia that was surgically corrected. PMID- 6246233 TI - [Spin immunoassay of urinary testosterone (author's transl)]. PMID- 6246235 TI - Incest: it's time we face reality. PMID- 6246234 TI - Nursing--a role in multidisciplinary treatment planning. PMID- 6246236 TI - Bisexuality: a sexual orientation of great diversity. PMID- 6246237 TI - Description of a crisis-oriented psychiatric home visiting service. PMID- 6246238 TI - Remarriage: parental perceptions of steprelations with children and adolescents. AB - This study was designed to determine if relationships between stepparents and adolescents differed from those between stepparents and younger children. Utilizing a questionnaire developed by Duberman, responses from remarried couples (N-50) were used to determine a steprelationship score for each child. The scores for children under age 13 and 13 and over both at the time of the parental marriage termination and the remarriage were compared. Chi-square techniques were used in the data analysis. No significant differences were found between the two groups. The results of this study suggest that factors, other than the child's age, may influence the steprelationship. Possibilities suggested include unresolved conflicts in the child and/or parents, the child's relationship with one or both natural parents, or the natural parents' relationship. This population merits further research consideration as society attempts to assimilate the growing number of these families. PMID- 6246239 TI - Effect of menadione (vitamin K3) on the metabolism of human polymorphonuclear leukocytes. PMID- 6246241 TI - Dietary fiber: the Institute of Food Technologists's Expert Panel on Food Safety and Nutrition and the Committee on Public Information, Chicago. PMID- 6246240 TI - The effects of coal fly ash and silica inhalation of macrophage function and progenitors. PMID- 6246242 TI - A physical, genetic and transcriptional map of the cloned his3 gene region of Saccharomyces cerevisiae. PMID- 6246243 TI - A restriction map of the T4 transfer RNA gene cluster. PMID- 6246244 TI - The cloning of a T4 transfer RNA gene cluster. PMID- 6246245 TI - The generation and analysis of clones containing bacteriophage T4 DNA fragments. PMID- 6246246 TI - The role of calcium in the control of myocardial contractility: an update. PMID- 6246247 TI - Localization of Na-K-ATPase in guinea-pig myocardium. PMID- 6246248 TI - Adenosine depresses contractility and stimulates 3',5' cyclic nucleotide metabolism in the isolated frog ventricle. PMID- 6246249 TI - The influence of resting membrane potential on the effect of verapamil on atria. PMID- 6246250 TI - Effect of tunicamycin on herpes simplex virus glycoproteins and infectious virus production. AB - The antibiotic tunicamycin, which blocks the synthesis of glycoproteins, inhibited the production of infectious herpes simplex virus. In the presence of this drug, [14C]glucosamine and [3H]mannose incorporation was reduced in infected cells, whereas total protein synthesis was not affected. Gel electrophoresis of [2-3H]mannose-labeled polypeptides failed to detect glycoprotein D or any of the other herpes simplex virus glycoproteins. By use of specific antisera we demonstrated that in the presence of tunicamycin the normal precursors to viral glycoproteins failed to appear. Instead, lower-molecular-weight polypeptides were found which were antigenically and structurally related to the glycosylated proteins. Evidence is presented to show that blocking the addition of carbohydrate to glycoprotein precursors with tunicamycin results in the disappearance of molecules, possibly due to degradation of the unglycosylated polypeptides. We infer that the added carbohydrate either stabilizes the envelope proteins or provides the proper structure for correct processing of the molecules needed for infectivity. PMID- 6246251 TI - Glycopeptides of murine leukemia viruses. II. Comparison of xenotropic and dual tropic viruses. AB - The glycosylation patterns of the gp70 glycoproteins of xenotropic and dualtropic murine leukemia virus (MuLV) were compared with those of ecotropic viruses. Ecotropic viruses contain a large glycopeptide size class designated G1 (molecular weight, approximately 5100), and such glycopeptides were not detected in xenotropic viruses grown in mink cells nor in dual-tropic viruses grown in mouse or mink lung cells. Both xenotropic and dual-tropic MuLV had glycopeptide size classes designated G2, G3, and G4 (molecular weights, approximately 2900, 2,200, and 1,500, respectively). G2 glycopeptides of xenotropic and dual-tropic MuLV were shown to be resistant to endo-beta-N-acetylglucosaminidase H, whereas G3 and G4 glycopeptides were susceptible. The relative abudance of glycopeptide G3 was increased in xenotropic and dual-tropic viruses as compared with ecotropic viruses, whereas the relative amount of G4 was decreased in xenotropic viruses. The similarity in the glycosylation patterns of a number of xenotropic and dual tropic viruses suggests that glycosylation sites are highly conserved within the env gene products of each of these classes of viruses. PMID- 6246252 TI - Replication of bacteriophage M13. XV. Location of the specific nick in M13 replicative form II accumulated in Escherichia coli polAex1. AB - M13 replicative form II (RFII) DNA was prepared from Escherichia coli RS5052 (polAex1) cells in the late stage of infection, and the DNA sequence at the discontinuity was examined. The data presented here suggest that the single discontinuity in the late stage of infection RFII maps at the same position as the gene II protein nicking site on fd RFI which was determined in vitro (Meyer et al., Nature (London) 278:365-367, 1979) and has a 5' terminal nucleotide sequence identical to that at the nick produced by gene II protein in vitro. The discontinuity in the in vivo RFII appears to be a single break in the phosphodiester backbone, leaving a 3' OH terminus. RFII molecules containing a gap, i.e., missing nucleotides at the site of discontinuity, were not detected. PMID- 6246253 TI - Viral DNA in bursal lymphomas induced by avian leukosis viruses. AB - Avian leukosis viruses (ALV) induce malignant lymphoma of the bursa of Fabricius. Viral DNA in tumors and normal tissues from infected birds were analyzed by using restriction endonucleases. Viral DNA fragments diagnostic of the exogenous ALV were easily detected in tumors, uninvolved bursal tissue, kidney, and erythrocyte nuclei. Exogenous viral DNA was more difficult to detect in liver. Using a restriction endonuclease (SacI) which cleaves linear unintegrated ALV DNA in a single site to define integration sites in DNA from the various tissues, we were able to detect ALV DNA only in tumor tissue. We concluded that the proviral DNA detected in the various nontumor tissue must be integrated in multiple sites. The appearance of ALV integration sites uniquely in tumors suggests that they are clonal growths. Furthermore, the data suggested the presence of a single exogenous integration site for the ALV provirus in each of six early neoplastic bursal nodules. This provirus appeared to retain the organization of EcoRI and BamHI recognition sequences present in the genome of virus used to infect the birds. The ALV integration site appeared different in each of the tumors studied. In a widespread metastatic lymphoma, multiple ALV integration sites were found as well as structural alterations in at least some copies of the ALV provirus. PMID- 6246254 TI - Molecular cloning of Snyder-Theilen feline leukemia and sarcoma viruses: comparative studies of feline sarcoma virus with its natural helper virus and with Moloney murine sarcoma virus. AB - Extrachromosomal DNA obtained from mink cells acutely infected with the Snyder Theilen (ST) strain of feline sarcoma virus (feline leukemia virus) [FeSV(FeLV)] was fractionated electrophoretically, and samples enriched for FeLV and FeSV linear intermediates were digested with EcoRI and cloned in lambda phage. Hybrid phages were isolated containing either FeSV or FeLV DNA "inserts" and were characterized by restriction enzyme analysis, R-looping with purified 26 to 32S viral RNA, and heteroduplex formation. The recombinant phages (designated lambda FeSV and lambda FeLV) contain all of the genetic information represented in FeSV and FeLV RNA genomes but lack one extended terminally redundant sequence of 750 bases which appears once at each end of parental linear DNA intermediates. Restriction enzyme and heteroduplex analyses confirmed that sequences unique to FeSV (src sequences) are located at the center of the FeSV genome and are approximately 1.5 kilobase pairs in length. With respect to the 5'-3' orientation of genes in viral RNA, the order of genes in the FeSV genome is 5'-gag-src-env-c region-3'; only 0.9 kilobase pairs of gag and 0.6 kilobase pairs of env-derived FeLV sequences are represented in ST FeSV. Heteroduplex analyses between lambda FeSV or lambda FeLV DNA and Moloney murine sarcoma virus DNA (strain m1) were performed under conditions of reduced stringency to demonstrate limited regions of base pair homology. Two such regions were identified: the first occurs at the extreme 5' end of the leukemia and both sarcoma viral genomes, whereas the second corresponds to a 5' segment of leukemia virus "env" sequences conserved in both sarcoma viruses. The latter sequences are localized at the 3' end of FeSV src and at the 5' end of murine sarcoma virus src and could possibly correspond to regions of helper virus genomes that are required for retroviral transforming functions. PMID- 6246255 TI - Association of a murine 53,000-dalton phosphoprotein with simian virus 40 large-T antigen in transformed cells. AB - Serum raised against a mouse 53,000-dalton (53K) phosphoprotein precipitates both the 53K immunogen and simian virus 40 large-T from lysates of simian virus 40 transformed 3T3 cells. This serum, designated F5, does not recognize antigenic determinants on native or denatured large-T and precipitates large-T because the 53K phosphoprotein forms a stable complex with large-T. This complex sediments at 23S on sucrose density gradients, corresponding to a molecular weight of 600K to 1,000K, and appears to contain only 53K and large-T as major components. It is held together by noncovalent bonds and is located in the cell nucleus. All the 53K immunoprecipitated from cell lysates by F5 is present in the high-molecular weight complex, but large-T can be separated into a complexed and a free form on sucrose density gradients. The complexed form of large-T is more readily phosphorylated than the free form. We have been unable to detect an association of large-T with comparable host cell proteins during productive infections with simian virus 40. PMID- 6246256 TI - Biochemical and electron microscopic studies of the replication and composition of milker's node virus. AB - Replication of milker's node virus (MNV) DNA begins 4 to 8 h postinfection, continues to 30 to 36 h postinfection in the cytoplasm of infected, primary bovine embryonic kidney cells, and is accompanied by an inhibition of host nuclear DNA synthesis. Between 20 and 24 h postinfection, newly replicated genomes are incorporated into particles which cosediment with purified MNV. These biochemical measurements could be correlated with the development of MN virions as revealed by electron microscopic analysis of thin sections prepared from infected cells. Analysis of the DNA in purified MNV showed that the virions contained a double-stranded DNA molecule with a molecular weight of 85 x 10(6) to 87 x 10(6) and a guanine-plus-cytosine content of about 63%. After denaturation and sedimentation analysis of MNV DNA in alkaline sucrose gradients, three major DNA species were resolved. These species appeared to represent intact, terminally cross-linked genomes (approximately 75 to 80S); genomes bearing one nick (or with one cross-link removed) (60 to 65S); and complementary, denatured DNA strands released from cross-linked genomes bearing two nicks (or with both cross-links removed) (52 to 55S). Forty [35S]methionine-labeled polypeptides, ranging from approximately 200,000 daltons to 10,000 to 15,000 daltons, were detected by radioautography after polyacrylamide gel electrophoresis of the proteins present in detergent-solubilized MNV preparations. Treatment of MN virions with Nonidet P 40, beta-mercaptoethanol, and sonication released 10 polypeptides, which were apparently located on the surface of virions. Further fractionation of these released polypeptides, followed by electron microscopy and polyacrylamide gel electrophoresis, indicated that a 42,000- to 45,000-dalton polypeptide is a major component of the threadlike tubule structure present on the surface of MN virions. PMID- 6246257 TI - Polyamines in encephalomyocarditis virus. AB - Encephalomyocarditis virus contains approximately 200 molecules of putrescine, 100 molecules of spermidine, and 40 molecules of spermine which could neutralize 11% of the viral genome. The same polyamines are present in different proportions in the Krebs ascites tumor cell in which the virus was grown. PMID- 6246258 TI - Role of two particle types in bovine rotavirus morphogenesis. AB - The involvement of light (L) and dense (D) bovine rotavirus particle types during virus replication has been studied. It was found that infectious parental L virions are uncoated in vivo to a particle similar to native D particles. Differences in the rate of synthesis and relative yields of L and D particles in MDBK and MA-104 cells have been detected. Results from pulse-chase labeling experiments indicate that D particles serve as morphogenic precursors to the complete L virion. PMID- 6246259 TI - Baboon endogenous virus genome. I. Restriction enzyme map of the unintegrated DNA genome of a primate retrovirus. AB - A detailed restriction map was deduced for the genome of an endogenous retrovirus of a higher primate, that of baboon. The cleavage sites for 12 restriction enzymes were mapped. The unintegrated linear viral DNA intermediate that is produced by infection of permissive cells with baboon endogenous virus was isolated. Hybridization with a strong-stop complementary DNA probe demonstrated presence of a terminal repetition in the linear viral DNA. The positions of restriction sites for two particular enzymes, SmaI and XhoI, near each end were consistent with this result and indicated that the length of the repetition is 0.55 +/- 0.01 kilobase. The linear viral DNA had a unique restriction map indicating that it is not a set of random circular permutations of the RNA genome. From hybridization with a 3'-specific probe, the DNA restriction map was aligned relative to the 5'-to-3' orientation of the viral RNA. We observed a minor heterogeneity in a BamHI recognition site 1.95 kilobases from the right end of the linear map. PMID- 6246260 TI - Cell-free translation of avian erythroblastosis virus RNA. AB - Avian erythroblastosis virus (AEV) RNA rescued from nonproducer cells by superinfection with a helper virus is translated into three polypeptides in the messenger-dependent rabbit reticulocyte lysate. A 75,000 molecular weight polypeptide (P75AEV) is synthesized from 28S RNA and is encoded by the 5' section of the AEV RNA, including gag-related and AEV-specific sequences. The P75AEV synthesized in infected cells and the P75AEV synthesized in the cell-free system are electrophoretically identical. A 44,000 molecular weight polypeptide (P44AEV) is synthesized from 20-24S RNA, apparently from the 3' section of the AEV specific RNA sequence. A minor 37,000 molecular weight polypeptide (P37AEV) is synthesized from 20S AEV RNA. A comparison is drawn between the cell-free products of MC29 and AEV RNAs. PMID- 6246262 TI - Temperature-sensitive mutants of foot-and-mouth disease virus with altered structural polypeptides. I. Identification by electrofocusing. AB - The structural polypeptides of foot-and-mouth disease virus were analyzed by electrofocusing in a polyacrylamide gel containing 9 M urea. Three versions of the technique were used to accomodate the widely differing isoelectric points of the four polypeptides. VP2 was identified by comparing mature virus with procapsids. The selective actions of proteases on virions of two serotypes and on their 12S particles were examined. From this emerged a simple test for distinguishing the similarly sized polypeptides: VP1, VP2, and VP3. The effects of carbamylation and succinylation on the charge of the polypeptides were investigated. From the properties of polypeptides modified either chemically or by mutation, it was concluded that all amino acid substitutions that might be expected to cause a charge change would be detected except for neutral-to histidine substitutions in the most basic polypeptide, VP1. In a sample of 73 temperature-sensitive mutants, 11 classes of variant polypeptides were distinguished on the basis of charge. Their molecular weights were unchanged. Alterations were found in all structural polypeptides except VP4. Mutations affecting VP2 caused similar shifts in the precursor, VP0. PMID- 6246261 TI - Specificity of protein synthesis inhibitors in the inhibition of encephalomyocarditis virus replication. AB - Effect of protein synthesis inhibitors on encephalomyocarditis virus production in L-cells was studied. Inhibition of initiation by hypertonicity, harringtonine, or pactamycin decreased viral protein synthesis to a lesser extent than that of host. Virus yield was unaffected or actually enhanced by low concentrations of these inhibitors. On the contrary, the elongation inhibitors cycloheximide, anisomycin, and emetine, shown previously to inhibit viral protein synthesis preferentially, had a greater effect on virus yield than on overall protein synthesis. These results support our earlier proposal that the antiviral activity of cycloheximide derives from its specific effect on the rate of elongation of protein synthesis, and that elongation inhibitors in general may show varying degrees of specific antiviral activity. PMID- 6246263 TI - Temperature-sensitive mutants of foot-and-mouth disease virus with altered structural polypeptides. II. Comparison of recombination and biochemical maps. AB - The structural polypeptides of foot-and-mouth disease virus were digested with Staphylococcus aureus V8 protease in the presence of sodium dodecyl sulfate. The protease-resistant peptides derived from temperature-sensitive mutants were compared with those of the wild type by electrofocusing in a polyacrylamide gel. Covariation between the charge shifts of different peptides indicated that they shared common sequences: only five independent peptides in all were derived from VP1, VP2, and VP3, accounting for approximately 50% of the polypeptide sequences. In two instances, amino acid substitutions that caused similar shifts in the isoelectric point were found to be located in different peptides. However, 15 mutants that possessed identical shifts in VP2 could not be distinguished by peptide analysis. The polypeptides of revertants able to grow at the nonpermissive temperature were compared with those of the parental mutants. By this test, 6 of the 12 distinguishable classes of coat protein mutations were found to covary with temperature sensitivity. In addition to true revertants, several phenotypic revertants which possessed a second charge change, either in a different structural polypeptide or in a different region of the same polypeptide, were isolated. The orientation of the recombination map was deduced from the loci of the coat protein mutations. PMID- 6246264 TI - Comparative biochemical studies of type 3 poliovirus. AB - A study of the biochemistry of type 3 poliovirus strains which involves the examination of the virus-coded polypeptides in infected cells and the preparation of oligonucleotide maps is reported. The polypeptide patterns were shown to be a relatively stable property of virus strains and distinguished Sabin vaccine strains from wild strains of poliovirus type 3. This approach may be of value in deciding the origin (vaccine or nonvaccine) of field isolates of poliovirus. Oligonucleotide maps were found to be sensitive indicators of differences among strains and appear to form a basis for determining genetic relationships among strains. The nucleotide maps of two viruses isolated from human cases of paralytic poliomyelitis temporally associated with the administration of attenuated vaccine suggested a vaccine origin for the strain. In one case the nucleotide map was indistinguishable from that of the vaccine strain. PMID- 6246265 TI - Characterization of herpes simplex virus type 1 RNA present in the absence of de novo protein synthesis. AB - We used herpes simplex virus type 1 (HSV-1) DNA and restriction fragments of HSV 1 DNA covalently coupled to cellulose as a reagent to isolate for further characterization the major and minor HSV-1 immediate-early mRNA species in HeLa cells infected and maintained in the absence of de novo protein synthesis. Five major and several minor immediate-early mRNA species were characterized. One major species was a 4.2-kilobase mRNA mapping in the TR(S)/IR(S) region with its 3' end distal to the U(S) region; this mRNA encoded a 170,000-dalton polypeptide in vitro. A 2.8-kilobase mRNA, encoding a 120,000-dalton polypeptide, was mapped in the TR(L)/IR(L) region with its 3' end directed toward the U(L) region. Three 1.8-kilobase mRNA species were mapped. One, mapping in the IR(S) region with its 3' end in the U(S), encoded a 68,000-dalton polypeptide. One mapped in the TR(S) region and had its 3' end in the U(S) region; the third one encoded a 64,000 dalton polypeptide and mapped in the U(L) region near the IR(L) region. One minor species 5.2 kilobases in size was clearly detectable mapping in the U(L) region. Furthermore, there were indications that one or more immediate-early mRNA species approximately 3 kilobases in size hybridized to regions near the TR(L) and in or near the TR(S)/IR(S) regions. Nuclear immediate-early RNA mapped only in those regions where polyribosomal immediate-early mRNA mapped, although minor differences were seen. Finally, we demonstrated that at least three major immediate-early mRNA's-4.2 kilobases, 2.8 kilobases, and the 1.8-kilobase one mapping in the IR(S)/U(S) region-continued to appear on polyribosomes as functional mRNA late after infection. PMID- 6246266 TI - Patterns of viral DNA integration in cells transformed by wild type or DNA binding protein mutants of adenovirus type 5 and effect of chemical carcinogens on integration. AB - The integration pattern of viral DNA was studied in a number of cell lines transformed by wild-type adenovirus type 5 (Ad5 WT) and two mutants of the DNA binding protein gene, H5ts125 and H5ts107. The effect of chemical carcinogens on the integration of viral DNA was also investigated. Liquid hybridization (C(0)t) analyses showed that rat embryo cells transformed by Ad5 WT usually contained only the left-hand end of the viral genome, whereas cell lines transformed by H5ts125 or H5ts107 at either the semipermissive (36 degrees C) or nonpermissive (39.5 degrees C) temperature often contained one to five copies of all or most of the entire adenovirus genome. The arrangement of the integrated adenovirus DNA sequences was determined by cleavage of transformed cell DNA with restriction endonucleases XbaI, EcoRI, or HindIII followed by transfer of separated fragments to nitrocellulose paper and hybridization according to the technique of E. M. Southern (J. Mol. Biol. 98: 503-517, 1975). It was found that the adenovirus genome is integrated as a linear sequence covalently linked to host cell DNA; that the viral DNA is integrated into different host DNA sequences in each cell line studied; that in cell lines that contain multiple copies of the Ad5 genome the viral DNA sequences can be integrated in a single set of host cell DNA sequences and not as concatemers; and that chemical carcinogens do not alter the extent or pattern of viral DNA integration. PMID- 6246267 TI - Simian virus 40 T-antigen: identification of tryptic peptides in the C-terminal region and definition of the reading frame. AB - T-antigen (the simian virus 40 A cistron protein) was purified by immunoprecipitation and electrophoresis on polyacrylamide gels from monkey kidney CV-1 cells infected with simian virus S (SV-S), dl1263, or dl1265 and digested with trypsin. The tryptic peptides, labeled with [35S]methionine, [35S]cysteine, or [3H]proline, were fractionated either by chromatography on Chromobead-P resin or by two-dimensional electrophoresis and chromatography on cellulose thin layers. The T-antigen of SV-S was shown to give rise to a proline-rich (approximately 6 mol of proline) tryptic peptide which was absent in dl1265 T antigen and hence, on the basis of DNA sequence data, must originate from the C terminus of the SV-S protein. T-antigen from dl1265, but not SV-S, yielded a cysteine-rich terminal tryptic peptide. The presence of these cysteines caused the protein to be retarded during electrophoresis under the usual conditions in polyacrylamide gels. The T-antigen of dl1263 possessed the proline-rich tryptic peptide; the data are consistent with there being only one peptide altered by the deletion. Both deletion mutants produced a T-antigen that had a higher electrophoretic mobility than SV-S T-antigen but still a larger apparent molecular weight than was predicted by the DNA sequence. The major form of T antigen found in several lines of 3T3 cells transformed by these mutants was indistinguishable from the T-antigen found in infected cells, and in addition seemed to associate normally with the host-coded 53,000-dalton protein. Except for a minor form of T-antigen with a slightly lower mobility in gels but the same C-terminus, no other polypeptides were detected among the extracted and immunoprecipitated proteins whose electrophoretic mobility was affected by either deletion. PMID- 6246268 TI - Herpes simplex virus glycoproteins: isolation of mutants resistant to immune cytolysis. AB - Immune cytolysis mediated by antibody and complement is directed against components of the major herpes simplex virus (HSV) glycoprotein complex (molecular weight, 115,000 to 130,000), comprised of gA, gB, and gC, and against glycoprotein gD-all present on the surfaces of infected cells. Tests with a temperature-sensitive (ts) mutant of HSV-1 (tsA1) defective in glycoprotein synthesis at the nonpermissive temperature (39 degrees C) demonstrated that over 90% of mutant-infected cells maintained at 39 degrees C and treated with antibody and complement were not lysed, presumably due to the absence of viral glycoproteins on the surface of infected cells at this temperature. Furthermore, a small number of tsA1-infected cells could be detected among a large excess of wild-type virus-infected cells by virtue of their failure to be lysed at 39 degrees C by antibody and complement. Making use of the involvement of viral glycoproteins in immune cytolysis and the ability of cells infected with glycoprotein-defective mutants to escape cytolysis, we sought mutants defective in the expression of individual viral glycoproteins. For this purpose, antisera directed against the VP123 complex and against the gC and combined gA and gB glycoprotein subcomponents of this complex were first tested for their ability to lyse wild-type virus-infected cells in the presence of complement. Wild-type virus-infected cells were lysed after treatment with each of the three antisera, demonstrating that the gC glycoprotein and the combined gA and gB glycoproteins can act as targets in the immune cytolysis reaction. Next, these antisera were used to select for mutants which were resistant to immune cytolysis. Cells infected with wild-type virus which had been mutagenized with 2-aminopurine and incubated at 39 degrees C were treated with one of the three types of antisera (anti-VP123 complex, anti-gC, or anti-gAgB) and lysed by the addition of complement. Cells which survived immune cytolysis were plated, and virus in the resulting plaques was isolated. Plaque isolates were tested for temperature sensitivity of growth and altered cytopathic effects in cell culture at 34 degrees C (the permissive temperature) and 39 degrees C. A total of 73 mutants was isolated in this manner. Selection with glycoprotein-specific antisera resulted in a 2- to 16-fold enrichment for mutants compared with "mock" -selected mutants using normal rabbit serum. Phenotypically, 24 mutants were temperature sensitive for growth, 27 were partially temperature sensitive, and 22 were not temperature sensitive but exhibited markedly altered cytopathic effects at both permissive and nonpermissive temperatures. Nine mutants of each phenotype (temperature sensitive, partially temperature sensitive, and non-temperature sensitive) were selected at random for confirmatory immune cytolysis tests with the antisera used in their selection. Cells infected with eight of the nine mutants were shown to be significantly more resistant to immune cytolysis at the nonpermissive temperature than were the mock-selected mutants or the wild-type virus from which they were derived. PMID- 6246269 TI - Characterization of avian myeloblastosis-associated virus DNA intermediates. AB - The major species of unintegrated linear viral DNA identified in chicken embryonic fibroblasts infected with either the avian myeloblastosis-associated viruses (MAV-1, MAV-2) or the standard avian myeloblastosis virus complex (AMV-S) has a mass of 5.3 X 10(6) daltons. An additional minor DNA component observed only in AMV-S-infected cells has a mass of 4.9 X 10(6) daltons. The unintegrated linear viral DNAs and integrated proviruses of MAV-1 and MAV-2 have been analyzed by digestion with the restriction endonucleases EcoRI and HindIII. MAV-2 lacks a HindIII site present in MAV-1. These fragments have been compared to those generated by EcoRI and HindIII digestion of linear viral DNAs of AMV-S. Restriction enzyme digestion of AMV-S viral DNA produced unique fragments not found with either MAV-1 or MAV-2 viral DNAs. The major viral component present in AMV-S stocks has the HindIII restriction pattern of MAV-1. Restriction enzyme analysis of the 5.3 X 10(6)-dalton unintegrated MAV viral DNAs and their integrated proviruses suggests that the DNAs have a direct terminal redundancy of approximately 0.3 megadaltons and integrate colinearly with respect to the unintegrated linear DNA. PMID- 6246270 TI - Relationship of retroviruses isolated from human leukemia tissues to the woolly monkey-gibbon ape leukemia viruses. AB - Retroviruses have been isolated from the tissues of human leukemia patients. Previous studies have shown that these isolates share some antigenic determinants with the family of viruses isolated from the woolly monkey and gibbon ape and that they exhibit partial nuclei acid homology with this same group of viruses. We have compared the RNAs of the viruses by two-dimensional polyacrylamide gel electrophoresis of the large RNase T1-resistant oligonucleotides. The degree of sequence identity between the RNAs was determined by the similarity of their RNase T1-resistant oligonucleotide pattern on gels, fingerprints, and in some cases by partial sequence analysis of individual oligonucleotides. This technique permits us to determine the degree of sequence identity among related RNA species. From our studies we conclude that viruses isolated from the tissues of two human leukemia patients, A1476 and SKA 21-3, as well as some subcultures of a virus isolated from the leukemic tissues of a third patient, HL23V, are closely related to the wooly monkey virus. However, the fingerprints of other HL23 viral isolates are very similar to that of GaLVSF, a gibbon ape leukemia virus isolated from a lymphosarcoma. PMID- 6246271 TI - Nucleotide sequence of the inverted terminal repetition in adeno-associated virus DNA. AB - The inverted terminal repetition in adeno-associated virus type 2 DNA has been sequenced. The terminal repetition contain 145 nucleotides of which the first 125 nucleotides can self-base pair to form a T-shaped hairpin structure. Both restriction endonuclease analysis with SmaI and BglI and direct sequence analysis of the SmaI fragments provide evidence for two sequences in the region of the terminal repetition between nucleotides 44 and 81. The two sequences represent an inversion of the first 125 nucleotides of the terminal repetition. Based on these data a model for adeno-associated virus DNA replication is presented which agrees in detail with a general model for eucaryotic DNA replication originally proposed by Cavalier-Smith (T. Cavalier-Smith, Nature [London] 18:672--684, 1976). PMID- 6246272 TI - Genome of porcine transmissible gastroenteritis virus. AB - The Purdue strain of transmissible gastroenteritis virus, a porcine coronavirus, was grown to titers of greater than 10(8) PFU/ml in a swine testicle cell line, and the RNA was isotopically labeled with [3H]uridine. The RNA was extracted from purified virus and was found to have the following properties. (i) It consisted primarily of a homogeneous large-molecular-weight species which electrophoretically migrated with an apparent molecular weight of 6.8 X 10(6) under denaturing conditions. (ii) It migrated electrophoretically at the same rate on nondenaturing gels before and after heat denaturation, suggesting that it does not consist of subunits. (iii) It was susceptible to pancreatic RNase A digestion in high (0.3 M) NaCl. (iv) It was polyadenylated to the extent that greater than 60% of the native RNA bound to oligodeoxythymidilic acid-cellulose under conditions of high (0.5 M) NaCl. RNA extracted from virions was infectious. This coronavirus can therefore be characterized as a positive-strand RNA virus. PMID- 6246273 TI - BK virus DNA sequence coding for the t and T antigens and evaluation of methods for determining sequence homology. AB - The DNA sequence of the early region of the human papovavirus BK (MM strain) was determined. A potential initiation signal for translation is located at nucleotides 3,047 to 3,045 or map position 0.614. Extending counterclockwise from this AUG signal there is only one open reading frame, which can code for a putative t antigen of 100 amino acids in length. If the early mRNA of BKV is spliced, then the regions between nucleotides 3,047 to 2,808 and 2,725 to 884 can code for a T antigen 694 amino acids in length. The sequences of the deduced T antigens in BK virus share 71% amino acid homology with those in simian virus 40, whereas the coding sequences of the two viruses share 70% DNA homology. Comparison of DNA sequences and evaluation of homology measurements between these two viruses are discussed. PMID- 6246274 TI - Novel p19-related protein in Rous-associated virus type 61: implications for avian gag gene order. AB - Virions of Rous-associated virus type 61 contain a previously unrecognized p19 related protein, called p19f, which comigrates with gag protein p12 during electrophoresis in sodium dodecyl sulfate-polyacrylamide gels but can be separated by gel filtration chromatography in 6 M guanidine hydrochloride. It is shown that the existence of p19f accounts for the earlier inability to order p27 and p12 by the pactamycin mapping procedure. Remapping with pactamycin by using methods which take this new protein into account yielded a gag gene order of NH2 p219-p27-p12-p15-COOH. It also confirmed earlier positions for the env and pol genes and placed unclassified protein p10 near a translational initiation site. The pactamycin-derived mapping position of p12 differs from reports based on tryptic analysis. An analysis of procedural shortcomings emphasizes the need for more definitive determinations of the avian gag gene order. PMID- 6246275 TI - Polypeptide synthesis and phosphorylation in Epstein-Barr virus-infected cells. AB - Epstein-Barr virus superinfection of the human lymphoblastoid cell line Raji, a Burkitt lymphoma-derived line that contains Epstein-Barr virus genomes in an episomal form, results in the sequential synthesis of 29 detectable proteins, which range in molecular weight from approximately 155,000 to 21,000, and in the shutoff of the bulk of host protein synthesis within 6 to 9 h after infection. There are three classes of virus-induced proteins; these are an early class, consisting of eight proteins synthesized by 6 h postinfection, an intermediate class, containing two proteins synthesized 9 h postinfection, and a late class, consisting of five proteins synthesized 12 h postinfection. In addition, there is a fourth class of polypeptides, called persistent, that are found both before and after superinfection. The rates of synthesis of the proteins fall into three patterns; these are pattern A, in which the rate of synthesis decreases, pattern B, in which the rate of synthesis remains steady, and pattern C, in which the rate of synthesis increases after the initial appearance of the polypeptide. Both 9-(2-hydroxy-ethoxymethyl)guanine (acyclovir) and phosphonoacetic acid inhibit the appearance of one intermediate protein and at least three late proteins. Seven polypeptides are phosphorylated at different times after infection. PMID- 6246276 TI - Assembly of avian reticuloendotheliosis virus: association of the core precursor polypeptide with the intracellular ribonucleoprotein complex. AB - A virus-specific ribonucleoprotein complex is present in the cytoplasm of reticuloendotheliosis virus-transformed chicken bone marrow cells. This ribonucleoprotein complex contains viral reverse transcriptase activity and may represent a precursor to the budding virion. The major viral polypeptide associated with the ribonucleoprotein complex was a polypeptide with a molecular weight of 63,000. This protein exhibited a precursor-product relationship with the major reticuloendotheliosis virus structural core protein p29. Core polypeptides were not associated with the intracellular ribonucleoprotein complex. Thus, p29 was incorporated into the virion in the form of its precursor Pr63. The cleavage of Pr63 in the ribonucleoprotein complex was accomplished either during the budding process of shortly after the release of particles from the cell. PMID- 6246277 TI - mRNA capping enzymes are masked in reovirus progeny subviral particles. AB - We examined the enzyme activities associated with progeny subviral particles isolated from L-cells infected with reovirus at 12 h postinfection. Activities normally present in reovirus cores were also found to be present in the progeny subviral particles, with the exception of the capping enzymes. The methylase and guanyl transferase activities, which constitute the capping system, were present in a masked form that could be activated by chymotrypsin digestion. The appearance of these progeny subviral particles in infected cells coincided with the time when mRNA synthesis was maximal, suggesting that viral mRNA synthesized at later times is uncapped. PMID- 6246278 TI - Immunoglobulin G(Fc)-binding receptors on virions of herpes simplex virus type 1 and transfer of these receptors to the cell surface by infection. AB - We have found that virions of herpes simplex virus type 1 have surface receptors capable of binding to the Fc region of immunoglobulin G and have also shown that the previously identified Fc-binding glycoprotein (designated gE) is present in extracts prepared from purified virions. The technique of affinity chromatography was used to detect gE. Two approaches were used to demonstrate the presence of Fc binding receptors on intact virions. First, it was shown that [125I] immunoglobulin G, but not [125I]F(ab')2 fragments, cosedimented with virions in sucrose gradients and, second, electron microscopy was done to show that soluble peroxidase-antiperoxidase complexes bound to virions. The use of peroxidase antiperoxidase complexes also permitted us to demonstrate that Fc-binding receptors from input (parental) virions become incorporated into the surface membranes of infected cells. This occurs presumably as a consequence of fusion between the virion envelope and cell surface membrane. PMID- 6246279 TI - Physical map of Caulobacter crescentus bacteriophage phi Cd1 DNA. AB - A restriction map of the Caulobacter crescentus bacteriophage phi Cd1 genome was constructed by using the restriction endonucleases HindIII and HpaI. A total of 12 fragments, ranging in molecular weight from 7.7 X 10(6) to 0.25 X 10(6), were produced by HindIII, and 7 fragments, ranging in molecular weight from 9.0 X 10(6) to 0.24 X 10(6), were generated by HpaI. The molecular weight of the genome was estimated to be approximately 28.8 X 10(6) on the basis of the relative electrophoretic mobilities of the restriction fragments. The relative order of the cleavage fragments was determined by specific cleavage of isolated restriction fragments, terminal labeling of both the whole genome and isolated fragments, and hybridization of isolated fragments to restriction fragments generated by other restriction enzymes. The genome of phi Cd1 was found to be terminally repetitive, and analysis of previously determined in vivo and in vitro RNA transcripts showed that the restriction map could be oriented such that transcription began on the left and proceeded to the right end of the genome. PMID- 6246280 TI - Site on the vesicular stomatitis virus genome specifying polyadenylation and the end of the L gene mRNA. AB - The 5'-terminal nucleotide sequence from positions 50 to 130 of vesicular stomatitis virus RNA was determined indirectly by using a defective interfering particle RNA which contains covalently linked genomic minus and antigenomic plus sense RNAs. The last 18 nucleotides of the L gene coding for in the viral polymerase were identified and isolated by specific duplex formation between 5' terminally labeled oligonucleotides from a small single-stranded defective interfering particle RNA and L gene mRNA. The L gene ends at position 60 from the 5' terminus of the vesicular stomatitis genome. The data demonstrated that the first seven adenine residues in the polyadenylic acid tail of L gene mRNA may be coded for in the genome and suggested that the viral transcriptase itself may carry out polyadenylation, possibly by chattering at the uridine-rich sequence at the end of the L gene. Analysis of the 5'-terminal sequence of vesicular stomatitis virus genomic RNA revealed that it might fold into a complex secondary structure with possibly 62% of the bases paired. PMID- 6246281 TI - Effect of acyclovir [9-(2-hydroxyethoxymethyl)guanine] on Epstein-Barr virus DNA replication. AB - The effect of acyclovir [9-(2-hydroxyethoxymethyl)guanine] on Epstein-Barr virus (EBV) DNA replication in the lymphoblastoid cell lines P3HR-1 and Raji is reported. Acyclovir at a concentration of 100 microM completely inhibited EBV DNA synthesis in superinfected Raji cells, but did not inhibit DNA synthesis in mock infected cells. The number of EBV genome equivalents per cell in the virus producing cell line P3HR-1 was significantly reduced by acyclovir, whereas the number of latent EBV genomes in Raji cells was not affected by the drug. In situ cytohybridization performed on untreated P3HR-1 cultures revealed the presence of relatively large amounts of EBV DNA in 15 to 20% of the cells. After a 100 microM drug treatment, no P3HR-1 cells contained levels of EBV DNA detectable by in situ cytohybridization. Indirect immunofluorescence studies demonstrated that during treatment with 100 microM acyclovir for 7 days, the percentage of P3HR-1 cells expressing viral capsid antigen was reduced. The EBV DNA remaining in P3HR-1 cells after treatment with 100 microM acyclovir (approximately 14 genomes per cell) had the properties of covalently closed circular DNA with an average molecular weight of 108 X 10(6), as determined by contour length measurements. PMID- 6246282 TI - Modification of avian sarcoma proviral DNA sequences in nonpermissive XC cells but not in permissive chicken cells. AB - For the first time, we present evidence with restriction enzymes HpaII and MspI which indicates that the proviral DNA sequence of avian sarcoma virus is modified by methylation in a nonpermissive rat cell line but not in permissive chicken cells. Some of the endogenous viral sequences in the permissive cells were also methylated. No 5-methylcytosine could be detected in the unintegrated viral DNA. PMID- 6246283 TI - Specificity of initiation factor preparations from poliovirus-infected cells. AB - Crude initiation factor preparations from poliovirus-infected cells stimulated the translation of poliovirus RNA in vitro, but were inactive for the translation of host cell or vesicular stomatitis virus mRNA's. In contrast, similar preparations from either uninfected or vesicular stomatitis virus-infected cells supported the initiation of translation of host cell mRNA's and both viral mRNA's. These results reflect a specific alteration of some components(s) of the initiation factor preparation from poliovirus-infected cells which is consistent with the ability of the virus to inhibit the translation of host cell and vesicular stomatitis virus-directed protein synthesis. PMID- 6246284 TI - Biochemical characterization of endogenous type C virus information in differentiated and undifferentiated murine teratocarcinoma-derived cell lines. AB - Undifferentiated teratocarcinoma cells express sixfold-higher levels of endogenous xenotropic type C virus-related RNA than differentiated cells. Three species of polyadenylated viral RNA (35S, 24S, and 14S) have been identified in the undifferentiated teratocarcinoma cells. Paradoxically, neither viral particles nor viral proteins have been detected in these cells. PMID- 6246285 TI - A seroepidemiologic survey of three pronghorn (Antilocapra americana) populations in southeastern Idaho, 1975-1977. AB - Sera from 104 adult and 42 fawn pronghorn antelope (Antilocapra americana) from southeastern Idaho were tested against selected livestock pathogens. The numbers positive/numbers tested (% positive) were as follows: bovine virus diarrhea - adults 2/102 (2), fawns 0/41 (0);; infectious bovine rhinotracheitis - adults 27/101 (27), fawns 9/42 (22); parainfluenza 3 - adults 79/104 (76), fawns 22/42 (52); bovine adenovirus 7 - adults 42/103 (41), fawns 20/48 (48); bovine adenovirus 3 - adults 11/32 (34), fawns 4/14 (23); Anaplasma marginale - adults 1/104 (1), fawns 1/42 (2). There were no reactors to brucellosis, bluetongue, or epizootic hemorrhagic disease; The prevalence of reactors varied considerably for different locations and for different years. PMID- 6246286 TI - Experimental infection and serologic survey for selected paramyxoviruses in red winged blackbirds (Agelaius phoeniceus). AB - Red-winged blackbirds (Agelaius phoeniceus) were experimentally exposed to three avian paramyxoviruses: turkey parainfluenza virus, Yucaipa virus, and two strains of Newcastle disease virus. Aerosol exposure resulted in infection but exposure in food or drinking water rarely or never did. Tracheal swabs contained virus for up to eight days post exposure, cloacal swabs were negative. Transmission to contact birds occurred infrequently. Antibody response was of low titer and short duration. No hemagglutination inhibition activity against these viruses was found in 387 sera collected from red-winged blackbirds and tricolored blackbirds (Agelaius tricolor) trapped in six states. PMID- 6246287 TI - Brain metastases in small cell carcinoma. PMID- 6246288 TI - The Ca ion permeability of the cell membrane. PMID- 6246289 TI - [Therapeutic effect of pivmecillinam for acute simple cystitis (author's transl)]. PMID- 6246290 TI - [Autopsy study on disseminated herpes virus infection (author's transl)]. PMID- 6246291 TI - [Clinicopathological studies in patients with hepatocellular carcinoma. III. Clinical application of prognosis forecasting by computer (author's transl)]. PMID- 6246292 TI - [Clinicopathological studies in patients with hepatocellular carcinoma. IV. Principal component analysis of ten parameters for prognosis forecasting (author's transl)]. PMID- 6246293 TI - [Radiological and pathological correlations on the endobronchial submucosal lesions (author's transl)]. PMID- 6246294 TI - [Arteriography in islet cell tumor--including one case of glucagonoma (author's transl)]. PMID- 6246295 TI - [Recovery from various complications in chronic renal failure following renal allotransplantation (author's transl)]. PMID- 6246296 TI - [Basis of an early diagnosis of lung cancer and the current status of its treatment]. PMID- 6246297 TI - [Investigation on bronchial hypersensitivity to inhaled prostaglandin F2 alpha and acetylcholine (author's transl)]. PMID- 6246298 TI - Cholestasis and hepatic metastases: a factor contributing to extreme elevations of carcinoembryonic antigen. AB - Records of 19 autopsied patients with metastatic carcinoma were studied to elucidate the contribution to the elevation of antemortem plasma carcinoembryonic antigen (CEA) levels (range, 5.9--136,000 ng/ml) of 1) liver pathology and dysfunction, 2) tumor morphology and CEA content, and 3) tumor spread and location. Liver function tests and plasma CEA recorded within 8 weeks of death, autopsy records of tumor spread, liver weight (as an index of liver tumor mass), and histologic sections were reviewed. Tissue CEA was demonstrated in 15 patients by an immunoperoxidase method. Cholestasis was seen in histologic sections of tissue from 8 of 10 patients, and elevated bilirubin was seen in 7 of 10 patients with hepatic metastases and CEA levels greater than 1,000 ng/ml In contrast, histologically observed cholestasis and elevated bilirubin were seen in only 1 of 8 patients with CEA less than 500 ng/ml. A significant correlation was found between the plasma CEA level and histologically observed cholestasis (P less than 0.01). Serum bilirubin also correlated significantly (P less than 0.01), but alkaline phosphatase did not. Liver weight (tumor mass) showed a positive correlation with cholestasis (P less than 0.01) but not with circulating CEA. Markedly elevated plasma CEA levels (greater than 1,000 ng/ml) seen preterminally may partially reflect impaired excretion of CEA by the hepatobiliary system rather than, or in addition to, preterminal increase in CEA-producing tumor. PMID- 6246299 TI - Cytotoxicity on tumor cells of peripheral blood monocytes and tumor-associated macrophages in patients with ascites ovarian tumors. AB - Mononuclear phagocytes were isolated from the peripheral blood (PB) and ascites tumors of 35 patients with epithelial ovarian tumors. After 48 hours of incubation with the TU5 tumor, tumor-associated macrophages (TAM) and PB monocytes from cancer patients showed lower cytolytic activity than did control cells, but by 72 hours there was little difference between control and ovarian cancer effector cells. Primary ovarian carcinoma cultures were heterogeneous in their susceptibility to macrophage cytotoxicity. Tumor cells from 7 patients were significantly lysed by monocytes and macrophages, whereas four ovarian cancer cell preparations were resistant to cytotoxicity. A "feeding" effect of mononuclear phagocytes on non-lysable tumor cells was detected in terms of both lower [3H]thymidine-release values in the cytolysis assay and increased proliferation in cytostasis assays. Thus patients with ovarian carcinomatous ascites PB monocytes and TAM had impaired cytotoxicity against a tumor cell line, and primary ovarian carcinoma cultures were heterogeneous in their interaction with mononuclear phagocytes. PMID- 6246300 TI - Human nasopharyngeal carcinomas positive for Epstein-Barr virus DNA in North America. AB - Nasopharyngeal carcinomas (NPC) from 2 black patients and 1 Caucasian patient were positive for Epstein-Barr virus (EBV) DNA. Of the tumors, 2 were lymphoepitheliomas (undifferentiated NPC) and 1 was a moderately differentiated NPC. All 3 patients had high IgG titers against EBV early antigen and high IgG and IgA titers against virus capsid antigen (VCA). In one patient, the levels of anti-VCA IgA were different than those of anti-VCA IgG over the course of the disease. Our data support the association of EBV and NPC in North America. PMID- 6246301 TI - Cyclic adenosine 3',5'-monophosphate-independent phosphorylation of externally oriented plasma membrane proteins in transformed and nontransformed mouse embryo cell lines. AB - Thirty transformed and nontransformed mouse embryo cell lines were analyzed to determine if increased plasma membrane phosphorylation is a characteristic of all transformed cell lines. Nontransformed, virally and chemically transformed, and smooth surface-transformed cell lines derived from Swiss, BALB/c, AKR, or C3H mice were studied. Cyclic AMP-independent phosphorylation of plasma membrane proteins was comparable in nontransformed and simian virus 40 (SV40)-transformed Balb/3T3 cells, in nontransformed and 3-methylcholanthrene (MCA)-transformed C3H/10T 1/2 cells, and in nontransformed and MCA-transformed AKR-2B cells. In contrast, increased plasma membrane phosphorylation was observed in MCA- and smoooth surface-transformed Balb/3T3 cells and in SV40-transformed Swiss 3T3 cells compared to the respective nontransformed parent cell lines. These observations suggest that increased cyclic AMP-independent phosphorylation of externally oriented plasma membrane proteins is not a universal marker for the transformed phenotype. PMID- 6246302 TI - Carcinogenicity of N-methyl-N'-nitro-N-nitrosoguanidine to the livers and kidneys of rainbow trout (Salmo gairdneri) exposed as embryos. PMID- 6246303 TI - Protection of cats against feline leukemia virus-positive and virus-negative tumors by complement-dependent antibody. PMID- 6246304 TI - [Cyclic adenosine monophosphate concentration in the blood plasma in coronary arteriosclerosis and its relationship to the nature of the metabolic disorders]. AB - The concentrations of cyclic adenosine monophosphate (cAMP) in the blood plasma collected on an empty stomach were determined by the radiochemical method in 40 males from 37 to 72 years of age suffering from ischemic heart disease. The cAMP blood plasma content was significantly higher in patients with coronary atherosclerosis than in 20 healthy young persons of the control group. In patients with a diabetic character of the glycemic curve under conditions of the oral standard test for glucose tolerance, the concentration of cAMP in blood plasma was significantly higher than that in patients with normal or doubtful glycemic curves. PMID- 6246305 TI - [Cyclic 3,5-adenosine monophosphate content and calcium transport in the aorta in hypertension due to experimental renal insufficiency]. AB - The calcium, magnesium, and cyclic AMP content and 45Ca transport in the aorta and iliac artery and the mechanical properties of these vessels were studied in rats with experimental renal insufficiency. The development of hypertension was attended by an increase in the magnesium content in the vascular wall, a certain decrease in the cyclic AMP level, marked disturbance of 45Ca transport, and changes in the mechanical properties of the vascular wall. The use of dihydrotachysterol or a complex of sex steroids which correct calcium metabolism led to a decrease of arterial hypertension. It is suggested that disorder of calcium metabolism in chronic renal insufficiency plays an essential role in the inadequate regulation of the vascular tone and the development of hypertension. PMID- 6246306 TI - Ultrastructural and biochemical changes induced by progressive lipid peroxidation on isolated microsomes and rat liver endoplasmic reticulum. AB - Ultrastructural and biochemical alterations induced by progressive lipid peroxidation on rat liver endoplasmic reticulum and on isolated microsomes have been studied. Lipid peroxidation was followed by measuring the content of malonaldehyde and similar thiobarbituric acid-reacting substances in the control specimens and in specimens in which lipid peroxidation was stimulated by CCl4 or other prooxidant systems. Lipid peroxidation induced a remarkable decrease in aminopyrine demethylase activity and in the cytochrome P-450 content both in vivo and in vitro. Parallel to these observations, alterations in the assembly of the membranes of isolated rat liver microsomes and of in situ endoplasmic reticulum were followed by electron spin resonance and electron microscopy. Electron spin resonance revealed changes in the resonance spectra interpreted as solubilization of cytochrome P-450 from the membrane. Electron microscopy on fixed and sectioned, negatively stained and freeze-fractured specimens revealed membrane alterations that were progressive with time of peroxidation. These alterations consisted of: (1) increased membrane deformability; (2) local and progressive breakages on the membranes; and (3) loss of intramembranous particles on both fracture faces of the membranes. The results obtained with the different techniques are compared and discussed in light of the importance of the lipid environment for the structure and function of biologic membranes. PMID- 6246307 TI - Dietary fiber. PMID- 6246308 TI - Comment on "A review of federal primary alcoholism projects," and a reply. PMID- 6246309 TI - Pre-auricular oat cell carcinoma metastases. AB - The oat cell tumor is a particularly lethal form of bronchogenic carcinoma. Cutaneous metastases occur occasionally in the pre-auricular area. In addition to benign and malignant parotid lesions, the differential diagnosis of a pre auricular mass must now include metastatic disease, particularly if a history of a thoracic malignancy is elicited. We present two such cases of metastatic oat cell carcinoma in the pre-auricular region. PMID- 6246310 TI - Granular cell tumor: a clinicopathologic study of 110 patients. AB - The clinicopathologic features of 118 granular cell tumors (GCT) encountered at two affiliated hospitals were reviewed. A total of 110 patients were affected over this 32-year period of study (71 men, 39 women), and in 5% GCT were multiple. Patients ranged in age from 16 to 58 years (average 32 years) and were symptomatic for an average duration of 11 months prior to diagnosis. There was a greater than expected frequency of GCT among black patients (29%). Although tongue was the single most common anatomic site involved, relatively more GCT (44%) occurred in skin or subcutaneous tissue. Less common locations were breast parenchyma (10 cases), rectal mucosa and anus (6), vulva (4), esophagus and larynx (2 cases each). The correct preoperative diagnosis of this protean tumor was made in only three patients. GCT were surgically treated with the average diameter of resected tumor being 1.2 cm (range 0.2--3.5 cm). Pseudoepitheliomatous hyperplasia was noted in 11 tumors and in one vulvar GCT there was overlying in situ squamous cell carcinoma. Tumors were incompletely excised in 24 of 56 patients having adequate followup; only five of these 24 patients experienced a local recurrence of tumor. Malignant behavior was not observed. Results of histochemical and ultrastructural study are briefly discussed. The precise histogenesis of GCT is uncertain but Schwann cell origin is favored in most cases. PMID- 6246311 TI - Carcinomas arising in fibroadenomas: a report of two cases and a review of the literature. AB - Carcinomas arising in fibroadenomas are rare. Two such cases are being presented; one is of the ductal variety and the other, lobular. Both cases clearly demonstrate the overall configuration of fibroadenomas with foci of in situ and infiltrating carcinoma, the surrounding breast tissue being devoid of malignant changes. The diagnosis was clinically unsuspected in both cases and in only one of them was it suspected at the time of gross pathological examination. The intent of this presentation is to increase general awareness as to the existence of carcinomas arising in fibroadenomas and also to actively discourage the practice of rendering gross pathological diagnoses of fibroadenomas at table diagnosis, however innocuous these neoplasms may appear to be, without microscopic examination by frozen sections. PMID- 6246312 TI - Reception of the energy level in bacterial taxis. PMID- 6246313 TI - Model for the supercoiling reaction catalyzed by DNA gyrase. PMID- 6246314 TI - Subarachnoid-pleural fistula: unusual complication of thoracotomy. AB - A case of subarachnoid-pleural fistula caused by a traction injury of the intercostal neurovascular bundle during thoracotomy is presented. Headaches, air within the ventricles of the brain, and clear drainage from the chest catheter should alert the surgeon to the presence of a subarachnoid-pleural fistula. If spontaneous closure of the fistula does not occur after a brief trial of chest catheter drainage, early operative intervention is advised. PMID- 6246315 TI - [A year's experience at a colitis clinic]. PMID- 6246316 TI - Malignant tumors of salivary glands. A university experience. AB - The management of salivary gland neoplasms continues to be a challenging clinical problem. Despite recent advances in histopathological classification, agreement among head and neck surgeons concerning optimum treatment is lacking. In attempts to eradicate the more malignant varieties of these tumors, surgeons have performed radical and multilating surgery. Radiation therapy has not been considered efficacious in many centers. A review of 93 maligant salivary gland tumors from 1955 to 1973 at the University of California, San Francisco, suggests that these tumors may be more radiosensitive than once thought. Radiation therapy combined with conservative surgical procedures may be as successful and perhaps more rational treatment than radical surgery alone. PMID- 6246317 TI - [Amebic liver abscess : value of extemporaneous search for ameba]. PMID- 6246318 TI - The interaction of ketamine with the opiate receptor. PMID- 6246319 TI - Vasoactive intestinal polypeptide: increased tone, enhancement of acetylcholine release, and stimulation of adenylate cyclase in intestinal smooth muscle. PMID- 6246320 TI - The effects of thyrotropin releasing hormone and histidyl-proline diketopiperazine on delta-9-tetrahydrocannabinol-induced hypothermia. PMID- 6246321 TI - Thyrotropin-releasing hormone stimulates the release of melanotropin from frog neurointermediate lobes in vitro. PMID- 6246322 TI - The influence of phosphorylable molecules on calcium transfer in the rat ileum. PMID- 6246323 TI - Plasminogen activator activity by cultured bovine aortic endothelial cells. PMID- 6246324 TI - Effect of endogenous LH secretion on ovarian cyclic AMP and cyclic GMP levels in the rat. PMID- 6246325 TI - Newer approaches to diabetes diets: high-fiber diet. PMID- 6246326 TI - [Fibroadenoma intracanaliculare phyllodes (cystosarcoma phyllodes) of the breast]. PMID- 6246327 TI - [Evaluation of working environment in the textile industry. IV. Dust concentration in the air of the flax spinning and weaving plants]. AB - Evaluation of dust concentration in the air of spinning and weaving rooms was made by gravimetric sampling of dust in 3 flax plants, where short flax fibres (flax--tow) and long flax fibres were manufactured. Besides, the dispersion of dusts and concentration of free silica were determined. The highest concentration of dust (10 mg/m3) was found in hackling room, mixing mill, and the one where spreading machines are operated, while in the carding room it was - 7.0 mg/m3. In other shops the concentration was - 5.5 mg/m3. The dust in the air of spinning rooms contained 2.3% of free silica and 53% of its particles were smaller than 5 micrometers. In the weaving rooms it contained 1.6% of free silica and 57% particles were smaller than 5 micrometers. The geometric mean of dust concentration higher than MAC for vegetable dusts (4 mg/m3) was found in hackling mill, mixing mill and the one where spreading machines are operated. PMID- 6246328 TI - [Cytochemical and immunological studies in workers exposed to organic solvents of paints and varnishes. II. Metabolism of the neutrophils]. AB - In 39 workers, aged 24--56, occupationally exposed to organic solvents of paints and varnishes containing benzene, toluene and xylene, for 55--122 months, activity of peroxydase (Pox) and acid phosphatases (AcP) was determined. In addition, NBT test was carried out in peripheral blood neutrophils. Both AcP activity and spontaneous and stimulated NBT reduction were found to be increased. The authors believe that in people an insignificant exposure to organic solvents of paints and varnishes stimulates neutrophils metabolism. PMID- 6246329 TI - Directory of restriction endonucleases. PMID- 6246330 TI - Purification and properties of HindII and HindIII endonucleases from Haemophilus influenzae Rd. PMID- 6246331 TI - Purification and properties of the Bsp endonuclease. PMID- 6246332 TI - Purification and properties of the Bsu endonuclease. PMID- 6246333 TI - Purification and properties of the Bg1I and II endonucleases. PMID- 6246334 TI - Purification and properties of the complementary endonucleases DpnI and DpnII. PMID- 6246335 TI - Purification and properties of the BamHI endonuclease. PMID- 6246336 TI - Purification and properties of the HphI endonuclease. PMID- 6246338 TI - Purification and properties of the SstI endonuclease. PMID- 6246337 TI - Purification and properties of the Bst1503 endonuclease. PMID- 6246339 TI - Preparation and properties of immobilized sequence specific endonucleases. PMID- 6246340 TI - Purification and properties of pyrimidine dimer specific endonucleases from Micrococcus luteus. PMID- 6246341 TI - Assaying of organisms for the presence of restriction endonucleases. PMID- 6246342 TI - Purification and properties of a pyrimidine dimer-specific endonuclease from E. coli infected with bacteriophage T4. PMID- 6246343 TI - Exonuclease III of Escherichia coli K-12, an AP endonuclease. PMID- 6246344 TI - Endonuclease IV from Escherichia coli. PMID- 6246345 TI - Purification and properties of the human placental apurinic/apyrimidinic endonuclease. PMID- 6246346 TI - Purification and properties of Escherichia coli endodeoxyribonuclease V. PMID- 6246347 TI - Use of infectious DNA assays. PMID- 6246348 TI - The use of DNA fragments of defined sequence for the study of DNA damage and repair. PMID- 6246349 TI - Purification and properties of S1 nuclease from Aspergillus. PMID- 6246350 TI - Assay for type II restriction endonucleases using the Escherichia coli recBC DNase and duplex circular DNA. PMID- 6246351 TI - Purification and properties of the mung bean nuclease. PMID- 6246352 TI - Purification and properties of venom phosphodiesterase. PMID- 6246353 TI - Polynucleotide kinase exchange as an assay for class II restriction endonucleases. PMID- 6246354 TI - Separation and isolation of DNA fragments using linear polyacrylamide gradient gel electrophoresis. PMID- 6246355 TI - Use of preparative gel electrophoresis for DNA fragment isolation. PMID- 6246356 TI - RPC-5 column chromatography for the isolation of DNA fragments. PMID- 6246357 TI - Fractionation of DNA fragments by polyethylene glycol induced precipitation. PMID- 6246358 TI - A photographic method to quantitate DNA in gel electrophoresis. PMID- 6246359 TI - Two-dimensional agarose gel electrophoresis "SeaPlaque" agarose dimension. PMID- 6246360 TI - A general method for defining restriction enzyme cleavage and recognition sites. PMID- 6246361 TI - Rapid DNA isolations for enzymatic and hybridization analysis. PMID- 6246362 TI - Denaturation mapping. PMID- 6246363 TI - Terminal transferase-catalyzed addition of nucleotides to the 3' termini of DNA. PMID- 6246364 TI - Genetic rearrangements and DNA cleavage maps. PMID- 6246365 TI - Determination of fragment order through partial digests and multiple enzyme digests. PMID- 6246366 TI - Mapping viral mRNAs by sandwich hybridization. PMID- 6246367 TI - 5'-Labeling and poly(dA) tailing. PMID- 6246368 TI - Sequencing end-labeled DNA with base-specific chemical cleavages. PMID- 6246370 TI - Mapping the origin and terminus of replication of simian virus 40 DNA by pulse labeling. PMID- 6246369 TI - Sequence analysis of short DNA fragments. PMID- 6246371 TI - Electron microscopic methods for locating the origin and termination points for DNA replication. PMID- 6246372 TI - Transcription maps of adenovirus. PMID- 6246373 TI - Definition and mapping of adenovirus 2 nuclear transcription. PMID- 6246374 TI - Restriction fragments from Chlamydomonas chloroplast DNA. PMID- 6246375 TI - Template function of restriction enzyme fragments of phage M13 replicative form DNA. PMID- 6246376 TI - Mapping simian virus 40 mutants by marker rescue. PMID- 6246377 TI - Microinjection of early SV40 DNA fragments and T antigen. PMID- 6246378 TI - Assay of transforming activity of tumor virus DNA. PMID- 6246379 TI - The isolation and properties of CAP, the catabolite gene activator. PMID- 6246380 TI - Electron microscopy of proteins bound to DNA. PMID- 6246381 TI - General purification schemes for restriction endonucleases. PMID- 6246382 TI - Purification and properties of EcoRI endonuclease. PMID- 6246383 TI - NAD+ kinase from sea urchin eggs. PMID- 6246384 TI - Nicotinic acid adenine dinucleotide phosphate (NAADP+). PMID- 6246385 TI - Bacillus subtilis NADase and its specific protein inhibitor. PMID- 6246386 TI - NAD glycohydrolase from bovine seminal plasma. PMID- 6246387 TI - NAD glycohydrolases from rat liver nuclei. PMID- 6246388 TI - Poly(ADP-ribose) synthetase from rat liver nuclei. PMID- 6246389 TI - Poly(ADP-ribose) synthetase from calf thymus. PMID- 6246391 TI - Preparation of flavin 5'-phosphates using immobilized flavokinase. PMID- 6246390 TI - Preparation, characterization, and coenzymic properties of 5-carba-5-deaza and 1 carba-1-deaza analogs of riboflavin, FMN, and FAD. PMID- 6246392 TI - Continuous fluorescence assay, partial purification and properties of flavokinase from Megasphaera elsdenii. PMID- 6246393 TI - Preparation of 3-aminopyridine adenine dinucleotide and 3-aminopyridine adenine dinucleotide phosphate. PMID- 6246394 TI - Preparation of alpha-NADP+. PMID- 6246395 TI - Genetic studies on site-specific endodeoxyribonucleases in Bacillus subtilis: multiple modification and restriction systems in transformants of Bacillus subtilis 168. PMID- 6246396 TI - Physical map of Aspergillus nidulans mitochondrial genes coding for ribosomal RNA: an intervening sequence in the large rRNA cistron. AB - A detailed map of the 32 kb mitochondrial genome of Aspergillus nidulans has been obtained by locating the cleavage sites for restriction endonucleases Pst I, Bam H I, Hha I, Pvu II, Hpa II and Hae III relative to the previously determined sites for Eco R I, Hind II and Hind III. The genes for the small and large ribosomal subunit RNAs were mapped by gel transfer hybridization of in vitro labelled rRNA to restriction fragments of mitochondrial DNA and its cloned Eco R I fragment E3, and by electron microscopy of RNA/DNA hybrids. The gene for the large rRNA (2.9 kb) is interrupted by a 1.8 kb insert, and the main segment of this gene (2.4 kb) is separated from the small rRNA gene (1.4 kb) by a spacer sequence of 2.8 kb length. This rRNA gene organization is very similar to that of the two-times larger mitochondrial genome of Neurospora crassa, except that in A. nidulans the spacer and intervening sequences are considerably shorter. PMID- 6246397 TI - Site-specific deletion at the replication origin of the antibiotic resistance factor R1. AB - The recombinant plasmid pRK101 carrying the complete replication origin of the antibiotic resistance factor R1 suffers frequently a deletion of 218 base pairs, removing parts or all of the origin sequence. This deletion seems to occur always when the Pst-E fragment carrying the replication origin is inserted into the cloning vector pBR322 in an orientation where the direction of R1 replication is the same as that of the vector plasmid and frequently when it is inserted in the opposite direction. DNA sequence analysis around the junction site generated by the deletion in three independently isolated deletion mutants reveals that the deletion occurs at a specific site, namely the end of a 22 bp sequence which is repeated almost identically at the other end of a segment of 197 bp. During the deletion one repeat unit is removed whereas the other is retained. The DNA sequence included by the two repeats contains high symmetric structures, i.e. inverted repeats, direct repeats and palindromes which may represent regulatory sites of the origin. PMID- 6246398 TI - The construction and characterisation of plasmid vectors suitable for the expression of all DNA phases under the control of the E. coli tryptophan promoter. AB - A DNA fragment flanked in the E. coli genome by Hinf I sites and containing the E. coli tryptophan promoter-operator and nucleotides specifying the leader sequence and first seven amino acids of trp E, has been cloned in the Hind III site of pBR322 with the aid of Hind III linkers. The Hind III site upstream from the trp promoter in the transcriptional sense was deleted to generate a Hind III cloning vector, designated pWT111, suitable for the expression of cloned DNA sequences as fusion products. Derivatives of this plasmid were constructed, designated pWT121 and pWT131, whose Hind III cloning sites differ with respect to their translation phasing relative to the initiator ATG of the trp E gene. Both pWT121 and pWT131 have a higher copy number per cell than pWT111. The tetracycline genes of all three plasmids are under trp promoter control and could be used to monitor the transcription of foreign genes inserted at the Hind III site of the vectors. PMID- 6246399 TI - A jumping gene in streptomyces coelicolor A3(2). AB - The difficulty in mapping the gene for chloramphenicol resistance (cmlR) in Streptomyces coelicolor A3(2) stock strains is possibly due to its location on different sites of the chromosome in various mixed subclones. Fresh isolates from CmlR strains show single unequivocal locations of cmlR. The same holds for CmlR strains derived as revertants from CmlS variants. The two best established sites for cmlR are one between cysA and metA, the other at right of argA, possibly in the right empty arc of the map (Fig. 2). The cmlR gene was assumed to be on a transposon (SCTn1), together with a gene for arginine-succinate synthase (argG), a gene for chromosome transfer (tra) and a gene for aereal mycelium formation (amy). In a CmlR revertant, the cmlR gene appears disjoined from argG (Fig. 5), thus showing the ability of SCTnl to be split and partially transposed. The possible wide occurrence of transposons in the genus Streptomyces is discussed. PMID- 6246400 TI - Molecular cloning of heterologous chromosomal DNA by recombination between a plasmid vector and a homologous resident plasmid in Bacillus subtilis. AB - The difficulty experienced in the shotgun cloning of chromosomal DNA on plasmid vectors in Bacillus subtilis is analyzed and an explanation for this difficulty is offered based on an inherent property of competent cells which imposes a requirement of plasmid multimers in transformation of plasmid-free recipients (Canosi et al., 1978). A stratagem which uses cloning by recombination between the vector and a resident homologous plasmid is tested and shown to be successful. Several recombinant plasmids are obtained containing Bacillus licheniformis DNA fragments which complement aromatic amino acid mutants of Bacillus subtilis. The yield of recombinant clones ranges from 6.7 to 210 per microgram of chromosomal DNA, depending on the selection and the restriction endonuclease. The various trp clones obtained after cutting chromosomal DNA with BglII and BclI do not complement trpE and exhibit both orientations with respect to the vector. The location of several restriction endonuclease cleavage sites in the cloned trp fragments is presented, and their relationship to the genetic map of Bacillus licheniformis is described. PMID- 6246401 TI - Control of plasmid R6K copy numbers in isogenic rep+ and rep Escherichia coli strains. PMID- 6246402 TI - Physical mapping of Bacillus subtilis phage rho14 cloning vehicles: heteroduplex and restriction enzyme analyses. AB - Four deletion mutants of temperate Bacillus subtilis bacteriophage rho14 have been examined utilizing restriction enzyme and DNA heteroduplex methods. This has allowed the orientation and mapping of the deletions on the rho14 physical map. A continuous 15% of the genome contains functions not essential for bacteriophage viability. A 7% subsection of this region contains phage immunity functions. The deletions were found to range in size from about 2.2-3.3 kilobases. In addition, the deletion mutants retain a single Sal I restriction site, which is currently being used as a cloning site for recombinant DNA. We have located the Sal I site to be 400 basepairs from the immunity region. Thus, the clear- and turbid-plaque deletion mutants are all capable of being utilized as molecular cloning vehicles for Bacillus subtilis. PMID- 6246403 TI - Single-stranded conjugation in Escherichia coli K-12. PMID- 6246404 TI - Cloning of DNA of the rpoBC operon from the chromosome of Escherichia coli K12. AB - We provide evidence that, in terms of transcriptional organisation, the rpoBC operon carried by lambdarifd 18 accurately represents the corresponding region of the E. coli K12 chromosome. A restriction fragment of E. coli K12 chromosomal DNA carrying the genes rpoBC (encoding the beta and beta' subunits of RNA polymerase) and rplL (coding for ribosomal proteins L7/L12) was cloned in a lambda vector, and the resulting phage tested for gene expression. In common with the corresponding fragment of lambdarifd 18 DNA, the chromosomal fragment has no strong promoter for rplL or rpoBC transcription. Another new phage was constructed by adding, to the restriction fragment carrying the rplL rpoBC structural genes from lambdarifd 18, a sequence from the E. coli K12 chromosome which includes a promoter for these genes. As in lambdarifd 18 itself, this promoter is shared with rplJ but not with rplKA. The properties of the latter phage also show that the dominant rifampicin-resistance characteristic of lambdarifd 18 results from more than one mutation. PMID- 6246405 TI - Identification of a positive regulatory protein in Escherichia coli: the product of the cysB gene. AB - From the specialized transducing bacteriophage lambdacysB, recombinant phages lambdacysB242 and lambdacysB257 have been obtained, each of which carries an amber mutation in the cysB cistron. A comparison of polyacrylamide gel electrophoretic profiles of labelled extracts from uv-irradiated bacteria that had been infected with lambdacysB+ or with lambdacysB-amber phages, led to the identification of a 39,000-dalton polypeptide as the product of the cysB gene. The native protein was purified to near radiochemical purity and was found to be an oligomer with an isoelectric point close to pH 7. PMID- 6246406 TI - Viral hepatitis A and B: a seroepidemiological study of a non-hepatitic Sydney population. AB - The age-specific prevalence rates of hepatitis A and B virus markers in 683 patients of all ages with non-hepatitic illnesses admitted to a Sydney hospital over the period from 1971 to 1974 were determined. The pattern of prevalence rates of hepatitis A antibody (anti-HAV) appeared to be a cumulative one, with steadily increasing rates in patients up to the age of 40 years. Thereafter a large increase in prevalence occurred. In contrast, prevalence rates for hepatitis B virus (HBV) markers were fairly uniform for all age groups. Antibody to core antigen (anti-HBc) was the most frequent marker of HBV infection. Prevalence rates in subjects of non-Anglo-Saxon origin were higher for both HAV and HBV markers. PMID- 6246407 TI - A varicella vaccine? PMID- 6246408 TI - [Rotaviruses in diarrheal diseases]. PMID- 6246409 TI - [Disenchantment following the initial enthusiasm for endorphins?]. PMID- 6246410 TI - Marihuana for nausea and vomiting due to cancer chemotherapy. PMID- 6246411 TI - [Action of phytobacteriomycin and of its component streptothricins on Culex pipiens molestus Forsk. mosquito larvae and on phytopathogenic bacteria]. PMID- 6246412 TI - Sponge cell aggregation. AB - Dissociated sponge cell system has proved to be a useful model to study the process of cell aggregation both on cellular and subcellular level. The purpose of this review is to discuss recent results obtained from experiments with the marine sponge Geodia cydonium. Dissociated cells form functional aggregates during a process which can be sub-divided into three phases: first, formation of small primary aggregates in the presence of Ca2+; second, formation of secondary aggregates in the presence of an aggregation factor and third, reconstitution of a functional system of water-containing channels by rearrangement in the secondary aggregates. On subcellular level a series of macromolecules are known which are involved in the control of aggregation and separation of sponge cells: Aggregation factor, aggregation receptor, anti-aggregation receptor, beta glucuronidase, beta-glucuronosyltransferase, beta-galactosyltransferase, beta galactosidase and a lectin. These components might be linked in the following sequence: (a) Activation of the aggregation receptor by its enzymic glucuronylation; (b) Adhesive recognition of the cells, mediated by the aggregation factor and the glucuronylated aggregation receptor; (c) Inactivation of the aggregation receptor by its deglucuronylation with the membrane-associated beta-glucuronidase; (d) Cell separation due to either the loss of the recognition site (glucuronic acid) of the aggregation receptor for the aggregation factor or to an inactivation of the aggregation factor by the anti-aggregation receptor. The activity of the anti-aggregation receptor is most likely controlled by the Geodia lectin. The events leading to cell-cell recognition cause a change in the following metabolic events: Increase of oxygen uptake, decrease of cyclic AMP level, increase of cyclic GMP level and stimulation of programmed syntheses. PMID- 6246414 TI - Multistage functional system amplifying and spreading the effect of estradiol in rat uterus. AB - Estradiol is demonstrated to induce histidine decarboxylase, and histamine is shown to activate adenylate cyclase in rat uterus. Histamine and cyclic 3',5'-AMP mimic the effects of estradiol in that they enhance RNA synthesis, induce glycolytic enzymes and uterus imbibition. The data suggest that estradiol enhances by induction of histidine decarboxylase the formation of histamine, the latter activates adenylate cyclase providing accumulation of cyclic 3',5'-AMP, which, probably, induces glycolytic enzymes through phosphorylation of chromatin proteins, and mediates other estradiol effects. The chain of successively acting enzymes and mediators constitutes, obviously, a cascade amplifying estradiol action. Since histamine is known to act as an intercellular mediator, attempts were made to find out the distribution of estradiol histamine and cyclic 3',5' AMP among uterus cells. Autoradiography has shown that [3H]-estradiol is bound by the nuclei of myometrium cells, [3H]-histamine was found above the cytoplasm of these cells, E13H]-cyclic 3',5'-AMP is selectively bound by the cells of capillary endothelium of the uterus. The estradiol mediators seem to spread effect of hormone on cells of different types which form together a kind of multicellular functional system. PMID- 6246413 TI - The organization of DNA metabolism during the recombinational phase of meiosis with special reference to humans. PMID- 6246415 TI - [Diet therapy of hypercholsterinemia]. PMID- 6246416 TI - [Bulk materials in hyperlipoproteinemias]. PMID- 6246417 TI - Repair and mutagenesis of herpes simplex virus in UV-irradiated monkey cells. AB - Mutagenic repair in mammalian cells was investigated by determining the mutagenesis of UV-irradiated or unirradiated herpes simplex virus in UV irradiated CV-1 monkey kidney cells. These results were compared with the results for UV-enhanced virus reactivation (UVER) in the same experimental situation. High and low multiplicities of infection were used to determine the effects of multiplicity reactivation (MR). UVER and MR were readily demonstrable and were approximately equal in amount in an infectious center assay. For this study, a forward-mutation assay was developed to detect virus mutants resistant to iododeoxycytidine (ICdR), probably an indication of the mutant virus being defective at its thymidine kinase locus. ICpR-resistant mutants did not have a growth advantage over wild-type virus in irraidated or unirradiated cells. Thus, higher fractions of mutant virus indicated greater mutagenesis during virus repair and/or replication. The data showed that: (1) unirradiated virus was mutated in unirradiated cells, providing a background level of mutagenesis; (2) unirradiated virus was mutated about 40% more in irradiated cells, indicating that virus replication (DNA synthesis?) became mutagenic as a result of cell irradiation; (3) irradiated virus was mutated much more (about 6-fold) than unirradiated virus, even in unirradiated cells; (4) cell irradiation did not change the mutagenesis of irradiated virus except at high multiplicity of infection. High multiplicity of infection did not lead to higher mutagenesis in unirradiated cells. Thus the data did not demonstrate UVER or MR alone to be either error-free or error-prone. When the two processes were present simultaneously, they were mutagenic. PMID- 6246418 TI - Red blood cell and fibroblast membranes in Duchenne and myotonic muscular dystrophy. PMID- 6246419 TI - Red cell membrane protein phosphorylation in hemolytic anemias and muscular dystrophies. AB - We review our current understanding of membrane phosphorylation in normal and abnormal erythrocytes. The major phosphoproteins in red blood cell (RBC) membranes are spectrin (band 2), bands 3, 2.1, and 4.5, and glycophorin A. At least two protein kinases can be distinguished on the basis of their stimulation by cyclic AMP and salt; they are present both in the membrane and in the cytosol. Analysis of the conflicting data on endogenous membrane-protein phosphorylation in abnormal RBCs indicates a considerable variability of phosphorylation rates which largely depends on the manner of preparation of ghosts and enzyme assay conditions. This variability reflects differences in the partitioning of protein kinases between the membrane and cytosol, the specificity and accessibility of membrane-protein substrates, and reaction kinetics. We select examples of data from several hemolytic anemias to illustrate that precautions are needed to interpret abnormalities of membrane-protein phosphorylation properly; we discuss possible new methodological approaches. PMID- 6246422 TI - Delta-9-tetrahydrocannabinol (THC) as an antiemetic. PMID- 6246421 TI - Physical probes of biological membranes in studies of the muscular dystrophies. AB - This review deals with recent physical approaches to the study of biomembranes. First, current concepts of the structure and dynamic organization of biological membranes are considered. The theoretical basis and practical application of various physical probe techniques are then discussed with specific reference to their usefulness in studies of these membranes. Particular emphasis is given to electron spin resonance and fluorescence techniques and to the potential difficulties encountered in their use and interpretation. Finally, reports applying these physical probes to various aspects of the human muscular dystrophies are reviewed and our current information in this area is summarized. PMID- 6246420 TI - Red blood cell alterations in muscular dystrophy: the role of lipids. AB - Biochemical, morphologic, and biophysical studies support the concept that the red blood cell (RBC) membrane is altered in both myotonic muscular dystrophy (MyD) and Duchenne muscular dystrophy (DMD). These studies have not identified a primary metabolic defect that would explain the various alterations of membrane properties. Since the lipid milieu of the membrane affects most membrane properties, it has been extensively investigated in MyD and DMD. Although some studies have suggested specific lipid abnormalities, no reproducible alterations have been reported in the major lipid constituents of the RBC membrane in these disorders. These findings suggest that major alterations of the predominant membrane lipids are not involved in these diseases. Furthermore, studies of the RBC membrane do not provide definitive statements as to the inborn error of metabolism, whether proteins or lipid constituents are primarily affected, or even whether the described alterations are intrinsic to the membrane or are secondary to some circulating factors. Nevertheless, RBCs have proved useful in demonstrating the involvement of the plasma membrane in muscle disorders and should be important in defining how such membrane perturbations affect transport mechanisms. PMID- 6246423 TI - Delta-9-tetrahydrocannabinol (THC) as an antiemetic. PMID- 6246424 TI - Delta-9-tetrahydrocannabinol (THC) as an antiemetic. PMID- 6246425 TI - Sustained effectiveness of converting-enzyme inhibition in patients with severe congestive heart failure. AB - Eight patients with severe congestive heart failure refractory to conventional therapy, including vasodilators, were given captopril (seven patients) or teprotide (one patient). All had dyspnea, edema, elevated pulmonary wedge pressure (28.0 +/- 2.6 mm Hg), low cardiac index (1.6 +/- 0.1 liters per minute per square meter), and elevated levels of serum creatinine (2.3 +/- 0.2 mg per deciliter [203.3 +/- 17.7 mumol per liter]), blood urea nitrogen (48 +/- 5 mg per deciliter [17.1 +/- 1.8 mmol of urea per liter]), plasma renin activity (21 +/- 7 ng of angiotensin I per milliliter per hour), plasma angiotensin II (271 +/- 51 pg per milliliter), and plasma aldosterone (65 +/- 14 ng per deciliter). After one week of therapy, all indexes improved. Creatinine and p-aminohippurate clearances were also increased (P less than 0.01). Improvement was sustained (more than six months) and was associated with a statistically significant increase in the cardiac ejection fraction (12 +/- 3 to 26 +/- 7 per cent). With a mean follow-up of seven months, the New York Heart Association Functional Class has been reduced from IV to II, and the number of days of hospitalization to less than 10 per cent of that before captopril therapy. We conclude that captopril reduces afterload in advanced congestive heart failure and induces sustained improvements in clinical status and renal function. PMID- 6246426 TI - Alpha-adrenergic receptor subtypes. PMID- 6246428 TI - Progress in vasodilator therapy for heart failure. PMID- 6246427 TI - Beneficial effect of oral lithium carbonate in the treatment of pancreatic cholera syndrome. PMID- 6246429 TI - Hypothyroidism and polybrominated biphenyls. PMID- 6246430 TI - Abnormal adrenergic and cholinergic sensitivity in cystic fibrosis. PMID- 6246432 TI - Are small-cell carcinomas of the lung derived from neural crest? PMID- 6246431 TI - Release of inflammatory mediators from stimulated neutrophils. PMID- 6246433 TI - Extrarenal potassium disposal. PMID- 6246434 TI - Pores for thought. PMID- 6246435 TI - Molecular consequences of deletion formation mediated by the transposon Tn9. PMID- 6246436 TI - Evidence for fixed charge in the nexus. AB - The nexus or gap junction has been characterized as a low-resistance junction as well as a highly permeable junctional membrane to many molecules. The transfer of electrical current from one cell interior to another, the aqueous solubility of dyes used to trace cell to cell communication and the fact that these molecules move across the nexus more rapidly than the plasma membrane have led to the hypothesis of an aqueous channel in the junction. Both Ca2+ (ref.11) and H+ (ref. 12) are thought to alter nexal membrane conductance, and a voltage-sensitive gate has been demonstrated within the junction. Recently, Flagg-Newton et al. have concluded that mammalian junctions may contain fixed charge or be of smaller diameter than arthropod junctions. Here we have investigated these alternatives by examining the permeability of nexuses of septa of the median giant axon of Lumbricus terrestris with various derivatives of fluorescein. Both carboxyfluorescein and aminofluorescein were found to have depressed permeabilities relative to their predicted permeabilities based on molecular size and weight (MW). Flourescein diffusion was significantly suppressed in axons pre injected with aminofluorescein but carboxyfluorescein had no such effect (Table 1). These data suggest the existence of fixed anionic charge within the nexal channel which may have affinity for amino groups. PMID- 6246437 TI - Encephalomyocarditis virus infection of cultured murine pancreatic beta-cells. PMID- 6246438 TI - Smallpox: gone for good? PMID- 6246440 TI - Single channel recordings of K+ currents in squid axons. AB - Ionic currents from individual K+ channels in squid axon membrane have been recorded. At hyperpolarizing membrane voltages, unit events occur as widely spaced rectangular pulses with short interruptions. The frequency of occurrence of the units increases strongly when the membrane is depolarized. PMID- 6246439 TI - The lambda phage att site: functional limits and interaction with Int protein. AB - Site specific integrative recombination of bacteriophage lambda involves unequal partners. The minimal phage att site is composed of approximately 240-base pairs and four distinct binding sites for Int protein, at least three of which are crucial for function. This 'donor site' recombines efficiently with a smaller 'recipient site' that lacks the extensive interactions with Int protein. PMID- 6246441 TI - Model for antenatal diagnosis of beta-thalassaemia and other monogenic disorders by molecular analysis of linked DNA polymorphisms. AB - Polymorphisms of DNA restriction sites within the human fetal globin genes have been used to identify chromosomes that carry beta-thalassaemia genes in individuals heterozygous for this disease. This has allowed an antenatal diagnosis for beta-thalassaemia to be carried out by observation of the pattern of the inherited polymorphism of a linked DNA sequence not involved in the genetic pathogenesis of the disease. In the populations we have investigated there is no constant pattern of polymorphism that segregates with the beta thalassaemia gene. The use of linked polymorphisms should, therefore, be applicable to antenatal diagnosis both of beta-thalassaemia and of any other single-gene defect for which there is a DNA probe specific for a sequence linked to the affected locus. PMID- 6246442 TI - Host-dependent evolution of three papova viruses. PMID- 6246443 TI - Avian sarcoma virus-transforming protein, pp60src shows protein kinase activity specific for tyrosine. AB - The protein responsible for malignant transformation by avian sarcoma viruses (ASVs) has been identified as a phosphoprotein of molecular weight 60,000 designated pp60src (refs 1--4). It has been suggested that this protein has a functional role in cellular transformation involving the phosphorylation of cellular proteins, for it was discovered that specific immunoprecipitates from ASV-transformed cells that contain pp60src catalysed the transfer of phosphate from [gamma-32P]ATP to the heavy chain of rabbit immunoglobulin. Additional studies involving the cell-free synthesis of the ASV src protein further demonstrated that the presence of the src polypeptide correlated with that presence of a phosphotransferase activity. Our studies, involving the biochemical purification of this protein, have demonstrated that the ASV-transforming gene product, pp60src, is itself a protein kinase. We have purified the pp60src protein approximately 5,000-fold using either conventional ion-exchange chromatography or immunoaffinity chromatography. The resultant partially purified preparations contain a cyclic AMP-independent protein kinase activity. We report here that the soluble phosphotransferase activity of partially purified pp60src results in the phosphorylation of exclusively tyrosine residues in a variety of proteins that serve as substrates. PMID- 6246444 TI - Drug receptors and their effectors. PMID- 6246445 TI - Isolation of the chicken thymidine kinase gene by plasmid rescue. AB - We have used the bacterial plasmid pBR322 as a vehicle to isolate genes coding for selectable markers from higher eukaryotes. In this way, we have obtained the chicken thymidine kinase (tk) gene as a 2.2-kilobase EcoRI/HindIII insert in BR322. The cloned gene transforms tk- animal cells with an efficiency equal to that of the cloned herpes simplex virus-1 tk gene. PMID- 6246446 TI - alpha 2-Adrenergic receptors appear in rat salivary glands after reserpine treatment. AB - The regulation of central and peripheral adrenergic receptors by various chemical, physiological, pharmacological and pathological stimuli has been the subject of intense study. For example, drug treatments can produce relatively small changes in the density of existing receptor binding sites in a variety of tissues. The alpha-adrenergic receptors in rat salivary gland tissue have been studied using radioligand receptor binding techniques. We have recently identified and characterised alpha 1-adrenergic receptors in the rat submandibular gland, but surprisingly, alpha 2-adrenergic receptor binding was not detectable. We now report that a single treatment of reserpine results in the appearance of alpha 2-adrenergic binding sites within 12 h. Continued treatment with the drug produces further increases in the number of alpha 2-adrenergic receptors, such that after 7 days the levels of alpha 1- and alpha 2-adrenergic receptors are similar. This is the first example of a drug treatment resulting in the appearance of a receptor type which was not previously detectable. PMID- 6246447 TI - Selective development of tolerance without dependence in multiple opiate receptors of mouse vas deferens. PMID- 6246448 TI - Murine leukaemogenesis: monoclonal antibodies to T-cell determinants arrest T lymphoma cell proliferation. AB - We have proposed a receptor-mediated leukaemogenesis hypothesis wherein T lymphomas would be clones of T cells bearing mitogen-linked surface receptors specific for the envelope determinants of the inducing MuLV. A prediction of the hypothesis is that T-lymphoma proliferation is dependent on continued presentation of MuLV envelope determinants to these cell-surface receptors, and that substances which interfere with receptor-virus interactions should inhibit T lymphoma proliferation. Rat monoclonal antibodies were raised to the AKR mouse T lymphoma KKT-2, and these antibodies were screened independently for blockade of virus-binding and for cytostatic activity on KKT-2 cells. We report here that those monoclonal antibodies which block virus binding inhibit growth of KKT-2 cells in vitro, whereas monoclonal antibodies which bind to these cells but do not block virus binding are not cytostatic. Three of the four cytostatic antibodies detect determinants on the Thy-1 molecule, while none of the other (noncytostatic) antibodies detect Thy-1. Antibody inhibition of KKT-2 cell growth is precluded by saturation of KKT-2 virus receptors with the inducing leukaemia virus. PMID- 6246449 TI - A nucleosome-free region in SV40 minichromosomes. PMID- 6246450 TI - Fidelity of DNA replication catalysed in vitro on a natural DNA template by the T4 bacteriophage multi-enzyme complex. AB - More than 50 copies of a phi X174 DNA template can be made in 60 min in an in vitro DNA replication system consisting of seven purfied replication proteins isolated from T4 bacteriophage-infected cells. By transfecting with the DNA products and assaying for the reversion of specific amber mutants, the high degree of base-pairing fidelity in this system is revealed; the in vitro system is also shown to respond to the mutagenic effect of Mn2+ and to display strong base-pair context effects on fidelity, as expected from in vivo studies. PMID- 6246451 TI - A herpes simplex virus type 1 function continuously required for early and late virus RNA synthesis. PMID- 6246452 TI - Differential stimulation of capped mRNA translation in vitro by cap binding protein. PMID- 6246453 TI - Construction in vitro and rescue of a thymidine kinase-deficient deletion mutation of herpes simplex virus. PMID- 6246454 TI - Red cell sodium fluxes catalysed by the sodium pump in the absence of K+ and ADP. AB - In the absence of extracellular Na+ or K+, the sodium pump catalyses an ouabain sensitive "uncoupled" Na+ efflux1-4. With red cell ghosts Glynn and Karlish5 showed that this Na+ efflux is accompanied by ATP hydrolysis and that extracellular sodium ions, at low concentrations, inhibit this efflux as well as the associated ATP hydrolysis. At higher concentrations, extracellular sodium ions restore the hydrolysis of ATP3,6 but it is not known whether there is an associated increase in Na+ efflux and, perhaps, an influx. To answer this question we have used inside-out red cell membrane vesicles which are specially suitable for controlling the composition of the medium at the two membrane surfaces while measuring 22Na+ fluxes in both directions. We report here that the sodium pump can operate in a mode in which influx and efflux of sodium are associated with ATP hydrolysis. This mode is different from the Na-Na exchange described by Garrahan and Glynn7, and Glynn and Hoffman8, which requires ADP as well as ATP9 and is probably associated with ADP-ATP exchage rather than ATP hydrolysis10,11. PMID- 6246455 TI - [Results of the treatment of small-cell undifferentiated bronchial carcinoma with combination radio and chemotherapy]. PMID- 6246456 TI - [Indications for orthotopic liver transplantation]. PMID- 6246457 TI - [Reactions of neurons of the primary somatosensory cortex in cats to stimulation of different vibrissae]. AB - Extracellular and intracellular reactions of 57 neurons from the vibrissal projection region in SI cortical zone were studied in cats. Intensity of both excitatory and inhibitory reactions decreased when stimulation of the receptive field was shifted from the centre to the periphery. A relative role of inhibition of vibrissal stimulation in inhibition/excitation interactions increased during such shift. Neurons recorded in the same microelectrode track had a common centre in the receptive field, but the dimensions of the receptive fields could differ substantially. Units with primary inhibition to the vibrissal stimulation were met. PMID- 6246458 TI - [Quantitative and qualitative characteristics of synapses in different layers of the auditory cortex]. AB - The electron-microscopic examination of synapses in different layers of the cat auditory cortex was performed. 53% of them were located on dendritic spines, 37% on dendrites and 10% on neuronal soma. All synapses were separated into type I and type II according to Gray. The type I synapses amounted to 91% (69.5% were of type Ia and 21.5% of type Ib), the type II synapses constituted 9%. The type I synapses were located mainly on dendrites and dendritic spines, the type II--on neuronal soma, axon hillocks and large dendrites. 60 h after complete neuronal isolation of a portion of the auditory cortex 22.8% of synapses revealed signs of degeneration. No type II degenerating synapses were found. This indicates that they are formed by axons of intracortical neurons. Quantitative and qualitative composition of synapses in different layers of the auditory cortex is shown to be different. PMID- 6246459 TI - [Effect of electrocutaneous stimulation on responses of neurons in the parvocellular portion of the medial geniculate body induced by acoustic stimulation]. AB - The effect of contralateral forepaw electrical stimulation on responses evoked by a click in neurons of the parvocellular part of the medial geniculate body was studied in cats anesthetized by thyopental sodium and immobilized with myorelaxine. Neurons in which responses to a click were inhibited by conditioning forepaw stimulation were located in areas of the parvocellular part of the medial geniculate body adjoining the ventro-posterior nucleus and the magnocellular part of the medial geniculate body. Forepaw stimulation did not affect the neurons located in lateral area of the parvocellular part of the medial geniculate body. In most neurons intracellular recording revealed EPSP-spike-IPSP or EPSP-IPSP sequence in response to a click while forepaw stimulation evoked exclusively IPSPs. Inhibition of neuronal responses to a click produced by forepaw stimulation may develop both during IPSP and without it. The mechanisms of inhibitory effect of forepaw stimulation on responses evoked by a click in neurons of the parvocellular part of the medial geniculate body are discussed. PMID- 6246460 TI - [Comparative analysis of the characteristics of potassium channels in the membranes of spinal ganglion neurons and neuroblastoma cells]. AB - The method of intracellular perfusion and voltage clamp was used to investigate potassium channels in the somatic membrane of the rat spinal ganglion neurons and mouse neuroblastoma cell. It is shown that potential-dependent properties of potassium channels in both types of membranes are similar while time constants of activation and inactivation are substantially higher in the neuroblastoma cells. The density of potassium channels was ten times less in the neuroblastoma cells than in the spinal ganglion neurons. PMID- 6246461 TI - [Blocking action of nickel, cobalt, manganese, and magnesium ions on the inward current through the potassium channel of Limnea stagnalis pond snail neurons]. AB - The dose-inward current relationship for calcium channel blocking ions of Ni, Co, Mn and Mg was studied by means of intracellular dialysis and voltage clamp in isolated neurons from the mollusc Limnea stagnalis. For all the four ions the effect was described by the Langmuir isotherm with KMn = 0.36 +/- 0.05 m,, KNi = KCo = 0.74 +/- 0.07 mM, KMg = 18.2 +/- 5.00 mM. These bivalent cations compete with current-carrying ions for a common binding site in the channel's entrance. PMID- 6246462 TI - Diagnosis of malignant tumors on the basis of the current generating capacity of malignant tumorous tissue. I. Examination in vitro, animal experiments and endoscopic measurements. AB - On the basis of the different electrolyte composition and lactic acid content of malignant tumorous tissue an electrochemical measuring method was worked out for the quick-diagnosis of malignant tumors. The in vitro model experiments and the measurings carried out on mice with Crocker's sarcoma proved the practicability of the electrochemical technique. The present study contains the measuring results of 55 adenocarcinomas and 12 scirrhous carcinomas. The current generating capacity of adenocarcinomas -- both with endoscopic measuring and that performed of samples excised -- exceeds the values measured in the healthy surrounding tissue with 45 to 50%. On the other hand, the generating capacity of scirrhous carcinoma is with 50% lower as the value measured in the healthy tissue. The generating capacity of gastric ulcer and polyp is virtually identical with that of the healthy gastric mucosa. The difference in generating capacity between the healthy tissue and malignant tumorous tissue is statistically significant. PMID- 6246463 TI - A patient with Verner-Morrison's syndrome--a vasoactive intestinal peptide (VIP) mediated watery diarrhoea syndrome? PMID- 6246464 TI - A comparison of composition and fluidity of multiple sclerosis and normal myelin. AB - Myelin was isolated from normal-appearing white matter from the brains of 11 multiple sclerosis (MS) patients, 11 normal individuals, and 1 patient with subacute sclerosing panencephalitis (SSPE). Ratios of protein, cholesterol, and phospholipid content, total fatty acid content, and total amino acid content were determined. The lipid bilayer fluidity of the myelin was measured using electron spin resonance and fluorescence polarization spectroscopy. The protein-to phospholipid ratio was higher than normal, the cholesterol-to-protein ratio was lower than normal while the cholesterol-to-phospholipid ratio was normal in MS myelin. This suggested a relative increase of protein to lipid content in MS myelin. Of the fatty acid content of a total lipid extract, MS myelin had relatively more 16:0, less 18:3, and less 22:3, 24:1 than normal. The total amino acid content of MS myelin was altered in a way which suggested a decreased percentage of basic protein and an increased percentage of proteolipids. SSPE myelin had similar changes in amino acid content but not in protein-to cholesterol or -phospholipid ratios or fatty acid content as MS myelin. There was no significant difference in myelin fluidity, however, between MS and normal myelin using fatty acid spin labels or fluorescent probes. A correlation was found between the fluidity and the cholesterol-to-phospholipid ratio but the MS and normal samples varied over a similar range. Although these alterations in lipid and protein composition had no effect on fluidity, they may nevertheless have serious consequences for myelin structure. PMID- 6246465 TI - [Method of studying conduction velocity in sensory fibers of the peripheral nerves and spinal cord. The averaging technic]. AB - The author describes a method of measuring conduction velocity in sensory fibres based on averaged evoked potentials. In the method potentials are recorded with surface electrodes over the nerves of the upper extremity at three sites: wrist, elbow and branchial plexus. The further route of the central neuron was represented by two responses from the cervical spinal cord at the C2 level, and first component N1 of the cortical response. The method makes possible distinguishing of damage to the peripheral part from that to the central part of the sensory system. Checking of the method in 15 healthy subjects made possible determination of conduction velocity which was stable for all measuring points in the peripheral nerve and spinal cord and was 75 m/sec, while at the distance from the spinal cord to the cortex it was only 58 m/sec. The author discusses in detail the technique of recording and reading of evoked potentials, whose amplitudes may be below 0.5 microV and latency is read with an accuracy of 0.1 msec. PMID- 6246466 TI - [Opiate receptors and sleep. Effects of microinjections of morphine in the median thalamus and the periaqueductal gray matter of the rabbit (author's transl)]. AB - Microinjections of morphine in optimal doses into the medial thalamus (40 micrograms) and periaqueductal gray matter (10-20 micrograms) produce slow-wave sleep with abondant spindles, in addition to analgesia. Like analgesia, the sleep inducing effect is blocked by naloxone (1 mg/kg i.v., 160 micrograms i.c.). One may therefore conclude that the effect is related to the agonistic action of morphine on endorphine receptors. It is thus probable that the endorphins constitute a regulatory system acting on the medullary-thalamic sleep-inducing structures which generate the sleep spindles. At higher dose levels, injections of morphine into the same structures produce behavioral agitation resembling the dissociated REM sleep described by Jouvet and which is not blocked by naloxone. The agitation might be due to an indirect action of morphine, and therefore of endorphin receptors, acting on monoaminergic structures. PMID- 6246467 TI - Cholinergic agonists and dibutyryl cyclic guanosine monophosphate inhibit the norepinephrine-induced accumulation of cyclic adenosine monophosphate in the rat cerebral cortex. PMID- 6246468 TI - Evidence for dynamic interactions between pituicytes and neurosecretory axons in the rat. PMID- 6246469 TI - Activities of alkaline phosphatase and Na+-K+-adenosine 5'-triphosphatase in the brain of experimentally produced histidinaemic squirrels (Funambulus palmarum). PMID- 6246470 TI - [Diet with a high content of alimentary fiber in the prevention and cure of constipation in pregnancy]. PMID- 6246471 TI - Metastatic gestational trophoblastic disease: secondary chemotherapy. PMID- 6246472 TI - Two cases of mucoepidermoid carcinoma of the liver in Chinese. AB - Two cases of mucoepidermoid carcinoma of the liver are presented. This tumour is a rare entity and is a variant of cholangiocarcinoma. Its prognostic significance does not appear to be different from that of other forms of cholangiocarcinomas which are encountered frequently in Hong Kong. PMID- 6246473 TI - [Enzymatic and morphologic changes in the pancreas, small intestine and liver of rats following ACTH administration and adrenalectomy]. PMID- 6246474 TI - Computed tomographic imaging of abdominal abnormalities in infancy and childhood. PMID- 6246475 TI - Metabolic adaptation in developing lung. AB - We have carried out studies using rat lung slices showing that the developing lung utilizes both glucose and fatty acids as oxidative substrates. Glucose oxidation to CO2 decreased at birth but showed higher activity after weaning. The activity of the pentose phosphate pathway also decreased postnatally. In contrast to glucose, the oxidation of palmitate and caprate to CO2 showed an increase in the immediate postnatal period. Cytochrome oxidase and carnitine palmitoyltransferase showed a parallel postnatal increase following the increase in fatty acid oxidation. Cytochrome oxidase activity in adult lung was approximately 30% of peak newborn values. Palmitate incorporation into total lipids was greatest at 18 to 19 days of fetal development, at which time the lung content of nonesterified fatty acids was highest. PMID- 6246476 TI - [Parainfluenzal encephalitis with predominant clinical symptoms of status epilepticus]. PMID- 6246477 TI - Intra-arterial infusions and intestinal necrosis in the rabbit: potential hazards of umbilical artery injections of ampicillin, glucose, and sodium bicarbonate. AB - Umbilical artery catheters are frequently employed for administration of medications. When the catheter tip is positioned adjacent to major aortic tributaries or inadvertently in the mesenteric arteries, high concentrations of infused substances may perfuse the intestine. Injections of saline, 50% dextrose, 10% dextrose, 8.4% sodium bicarbonate, and 100 mg/ml ampicillin were made into a branch of the mesenteric artery supplying 10 to 15 cm of rabbit ileum. The intestine was then examined two to five days later. All segments of intestine perfused with saline and 10% dextrose were grossly and microscopically normal. In each of the eight sites perfused with 50% dextrose, intestinal necrosis was noted (P less than .001). Four of eight sites perfused with ampicillin had hemorrhage and villus atrophy (p less than .001). Of the eight sites perfused with sodium bicarbonate, three had necrosis with hemorrhage and five had villus edema. The data indicate that intraarterial infusions of high concentrations of sodium bicarbonate, glucose, and ampicillin produce serious lesions in an animal model. This suggests that appropriate precautions should be exercised when administering medications through the umbilical artery catheter. PMID- 6246478 TI - [Herpes encephalitis treated using adenine-arabino-side and followed-up by densitometry (author's transl)]. AB - In a 52-year-old man suffering from encephalitis, immunofluorescent study of cerebral tissue led to a diagnosis of herpes encephalitis 4 hours after biopsy. Cell cultures on the fourth day confirmed the diagnosis. Such a hypothesis had already been advanced before biopsy on the basis of the electroencephalogram which showed electrical changes with a periodic tendency. Following treatment with adenine-arabinoside, motor deficit and aphasia disappeared in one month whilst there was a parallel increase in antibody levels in the blood and cerebrospinal fluid. PMID- 6246479 TI - Nutrition: bran or aperients? PMID- 6246480 TI - Metabolic aspects of psoriasis: the basis for specific therapy. AB - Psoriasis, like diabetes, is a multifactorial genetic disease with complex interactions of deranged metabolism. Factors that affect epidermal differentiation and proliferation include cyclic nucleotide interactions, polyamine metabolism, cell surface--cytoskeleton interactions, and arachidonic acid--prostaglandin cascade. Evidence indicates that pharmacologic manipulation of the so-called critical metabolic systems not only may help us to understand the pathophysiology of psoriasis but also may yield improved treatments for the disease. PMID- 6246481 TI - The effects of dietary cellulose and sand on the combined metabolic plus endogenous energy and amino acid outputs of adult cockerels. AB - Two experiments were made with adult, Leghorn cockerels to measure the effects of inert materials on metabolic plus endogenous (M+E) excretions. In the first experiment birds starved for 24 hr were force-fed 25 g of either a laying hen diet (OHR) or corn supplemented with 0, 1, 2, 3, or 4 g of cellulose. Excreta voided were collected quantitatively during the two 24 hr periods postfeeding. A group of 4 birds was maintained unfed. Diets and excreta were assayed for amino acids (AA) and gross energy (GE). Supplemental cellulose had no effects on AA excretion nor on the availabilities of the AA within the OHR and corn. All AA, in the form of feed residues, were excreted within 24 hr of feeding. During the period 24 to 48 hr postfeeding the OHR fed birds excreted more AA than did the corn fed birds, probably because they were less depleted in protein. The AA excretions of the unfed birds decreased with the duration of starvation. The true available AA values for the diets were calculated using a series of three corrections for M+E AA outputs. The true metabolizable energy (TME) values of the OHR and corn were unchanged by the cellulose which indicates that the cellulose contained no available energy and had no effect on the availability of the energy within the OHR and corn. It also demonstrated that the cellulose did not change the M+E energy excretion. The second experiment was a 4 X 4 factorial with four diets: nil, corn, wheat, oats (25 g/bird), and four levels of sand: 0, 1, 2, 3 g/bird. The birds were starved for 24 hr prior to feeding and excreta were collected quantitatively during the two 24 hr periods postfeeding. Feeding sand to the birds had no effect on their GE outputs but it was noted that little sand was voided within 48 hr postfeeding. The TME values were determined for the grains. A number of significant differences were observed but there was no evidence that the sand altered the TME values. It was therefore concluded that the sand had no effect on the M+E energy excretion of the assay birds. It is concluded that supplemental cellulose had no effect on the AA excretion of adult Leghorn cockerels. Neither cellulose nor sand, in the levels fed, altered M+E energy excretion. Neither diluent appeared to alter the utilization of the materials with which they were fed. PMID- 6246482 TI - Physiological effects of exogenous adrenocorticotropin injections in Japanese quail. AB - Administration of exogenous adrenocorticotropin (ACTH) into young Japanese quail resulted in certain physiological changes consistent with those which have been reported in chickens. These include reduced body weight gains and bursa weights. Also adrenal cholesterol values were decreased, and serum cholesterol and plasma refractive indices were increased. However, spleen weights, right adrenal weights, and packed cell volumes were not consistently altered at 24 hr post-ACTH administration. Collectively, these findings suggest that Japanese quail are less responsive to ACTH-induced adrenal hyperfunction than chickens. PMID- 6246483 TI - [Biological method of blood plasma glucagon determination]. AB - Biological method of glucagon determination in the blood plasma was worked out. The method consists in incubation of the rat liver membranes with glucagon which stimulates adenylcyclase, whose activity was determined by the accretion of cAMP content in the incubation medium. Membranes with increased sensitivity of glucagon were obtained; hormone concentrations in the plasma of healthy persons and of patients suffering from diabetes were determined. In healthy persons glucagon content varied from 54 to 175 pg/ml. PMID- 6246484 TI - [Relationship between the pineal body and the hypothalamo-hypophyseal system. V. Melatonin inhibition of the gonadotropic activity of the hypothalamo-hypophyseal system]. AB - Effect of melatonin on the gonadotropic activity of the hypothalamo-hypophysial system was investigated. The following proved to occur under the action of melatonin in sexually immature female rats: reduction of the spontaneous activity of luteinizing hormone (LH), of the LH content in the hypophysis, and of the endogenous luliberin stores in the arcuate nucleus; response of the hypophysis to the exogenous luliberin was also diminished. Single administration of low doses (from 1 to 100 micrograms) of melatonin was accompanied by reduction of cAMP content in the hypophysis and the hypothalamus. LH, luliberin and cAMP were determined by radiochemical methods. The results obtained indicated that the inhibitory influence of the pineal gland on the reproductive system was realized by melatonin, its hormone, through the hypothalamo-hypophysial complex. PMID- 6246485 TI - Electron paramagnetic resonance crystallography of 17O-enriched oxycobaltomyoglobin: stereoelectronic structure of the cobalt dioxygen system. AB - An electron paramagnetic resonance crystallographic study was made on oxycobaltomyoglobin with the dioxygen ligand enriched to 19.1% in (17)O. There are two spectroscopically distinct cobalt dioxygen species. The less abundant species, II (40%), has nonequivalent oxygen atoms with superhyperfine tensors (O)A(alpha) = (5, -67.5, 22.4)G and (O)A(beta) = (5.4, -83.3, 30.3)G. Together with the previously reported (59)Co hyperfine tensor [Chien, J. C. W. & Dickinson, L. C. (1972) Proc. Natl. Acad. Sci. USA 69, 2783-2787], the orbital spin densities are found to be O(alpha)(p(eta)) = 0.48, O(alpha)(p(zeta)) = 0.11, O(beta)(p(eta)) = 0.74, O(beta)(p(zeta)) = -0.16, Co(d(xz)) = -0.01, Co(d(yz)) = 0.06 for a total electron density of 1.01. The O-O axis is directed toward His-E7, suggesting a possible hydrogen bonding interaction which may contribute to the nonequivalency of the oxygen atoms; its projection approximately bisects N(1)-Fe-N(2). The z axis of the (Co)A tensor is tilted at an angle of 28 degrees from the heme normal, resulting in a Co-O-O angle of 120 degrees . The more abundant species, I (60%), has equivalent oxygen atoms with (O)A(gamma) = (12, -72.5, 20)G and orbital spin densities of O(gamma)(p(eta)) = 0.54, O(gamma)(p(zeta)) = -0.05, Co(d(xz)) = -0.02, Co(d(yz)) = 0.09 for a total spin density of 1.10. Although the direction cosines for this molecule cannot be precisely determined, the projection of its O-O axis approximately bisects N(2) Fe-N(3) and is parallel to the imidazole ring of His-F8. Increase of temperature changes g, (Co)A, and (O)A values, with the largest effect seen with (O)A. This temperature dependence indicates averaging of the two bond structures which are stabilized at 77 K. PMID- 6246486 TI - Purification from rat sarcolemma of the saxitoxin-binding component of the excitable membrane sodium channel. AB - The saxitoxin-binding component (SBC) of the excitable membrane sodium channel has been solubilized and purified from rat skeletal muscle sarcolemma. Phospholipid was required in mixed micelles with detergent for stability of the mammalian SBC. Even at optimal detergent-to-phospholipid ratio, the solubilized SBC showed significant temperature-dependent loss of specific toxin binding with time, necessitating maintenance of low temperatures during purification. Characteristics of saxitoxin binding to the solubilized material closely resembled those seen in intact membranes. A weak anion-exchange column was synthesized; it provided rapid 10- to 20-fold purification of the solubilized SBC. Additional necessary purification was obtained by chromatography on immobilized wheat germ agglutinin. Specific saxitoxin-binding activity of the purified material averaged approximately 1500 pmol of saxitoxin bound per mg of protein. Three bands were present in this material on sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The purified material sedimented on a sucrose gradient with an apparent s20,w of 9.9 S. PMID- 6246487 TI - Transforming gene product of Rous sarcoma virus phosphorylates tyrosine. AB - The protein kinase activity associated with pp60src, the transforming protein of Rous sarcoma virus, was found to phosphorylate tyrosine when assayed in an immunoprecipitate. Despite the fact that a protein kinase with this activity has not been described before, several observations suggest that pp60src also phosphorylates tyrosine in vivo. First, chicken cells transformed by Rous sarcoma virus contain as much as 8-fold more phosphotyrosine than do uninfected cells. Second, phosphotyrosine is present in pp60src itself, at one of the two sites of phosphorylation. Third, phosphotyrosine is present in the 50,000-dalton phosphoprotein that coprecipitates with pp60src extracted from transformed chicken cells. We infer from these observations that pp60src is a novel protein kinase and that the modification of proteins via the phosphorylation of tyrosine is essential to the malignant transformation of cells by Rous sarcoma virus. pp60sarc, the closely related cellular homologue of viral pp60src, is present in all vertebrate cells. This normal cellular protein, obtained from both chicken and human cells, also phosphorylated tyrosine when assayed in an immunoprecipitate. This is additional evidence of the functional similarity of these structurally related proteins and demonstrates that all uninfected vertebrate cells contain at least one protein kinase that phosphorylates tyrosine. PMID- 6246488 TI - Supercoils in prokaryotic DNA restrained in vivo. AB - Cells of Escherichia coli containing the plasmid F were gamma-irradiated with various doses to introduce determined numbers of single-strand breaks in the F DNA. The cells were then incubated to permit repair of the breaks while DNA gyrase was inhibited with coumermycin to limit restoration of any relaxed supercoil. Repaired, covalently continuous F DNA was isolated and its superhelical density was measured by two different methods. Both indicated that a major part (50-60%) of the negative superhelical turns were maintained in the repaired molecules, suggesting that the supercoils are restrained in vivo. PMID- 6246489 TI - Polyoma large tumor antigen is not required for tumorigenesis mediated by viral DNA. AB - The arrangement of viral DNA sequences in a hamster cell line derived from a tumor induced by a recombinant plasmid DNA preparation containing the entire polyoma virus genome was examined. In the recombinant plasmid employed, viral DNA sequences specifying the large species of polyoma tumor antigen but not the small and middle tumor antigens were interrupted by the insertion of plasmid DNA at the EcoRI restriction endonuclease site. Blot-hybridization analyses of tumor cell DNA indicated that the "joints" linking viral and plasmid DNAs in the original recombinant plasmid used in animal inoculation had been preserved. Integration into the hamster cell genome had apparently occurred within plasmid DNA sequences. These results indicate that polyoma large tumor antigen is not required for tumorigenesis mediated by viral DNA. PMID- 6246491 TI - A small RNA induced late in simian virus 40 infection can associate with early viral mRNAs. AB - Analysis of total cytoplasmic and polyadenylylated cytoplasmic RNA from cells lytically infected with simian virus 40 (SV40) has demonstrated the presence of a small RNA, approximately 65 nucleotides long, that is induced late in lytic infection. This small RNA is apparently specific in size and sequence and is not selected on columns of oligo(dT)-cellulose. It is homologous to a region of the early SV40 mRNAs (and to the late DNA strand), starting approximately 250 nucleotides from the 3' end of the early mRNAs (SV40 map position 0.21). The function of this RNA in the viral cycle and its source are unknown at this time; however, its temporal expression, unique sequence, and interesting region of homology within the SV40 genome suggest a possible role in the control of SV40 gene expression. PMID- 6246490 TI - Mepacrine blocks beta-adrenergic agonist-induced desensitization in astrocytoma cells. AB - C6 astrocytoma cells contain beta-adrenergic receptors coupled to adenylate cyclase. A 2-hr exposure to l-isoproterenol results in an 80% decrease in cyclic AMP production in response to a subsequent challenge by l-isoproterenol (desensitization). This loss in responsiveness is paralleled by a 20-30% decrease in the apparent number of beta-adrenergic receptors and by increased release of arachidonic aciid into the medium. The increased release of arachidonic acid is caused by the action of phospholipase A2 (phosphatide 2-acylhydrolase, EC 3.1.1.4) and corresponds to increased turnover of methylated phospholipids. Mepacrine and tetracaine, both inhibitors of this phospholipase A2, are able to block l-isoproterenol-induced desensitization of cyclic AMP production and the decrease in beta-adrenergic receptors. Mellitin and phorbol ester, two activators of phospholipase A2, when preincubated with the cells cause a decreased cyclic AMP response of the cells to l-isoproterenol. These results suggest that the activation of phospholipase A2 in the local domain of the beta-adrenergic receptor may be involved in desensitization. PMID- 6246492 TI - Ubiquitous, interspersed repeated sequences in mammalian genomes. AB - DNA base sequence comparisons demonstrate that the principal family of 300 nucleotide interspersed human DNA sequences, the repetitive double-strand regions of HeLa cell heterogeneous nuclear RNA, and specific RNA polymerase III in vitro transcripts of cloned human DNA sequences are all representatives of a closely related family of sequences. A segment of approximately 30 residues of these sequences is highly conserved in mammalian evolution because it is also present in the interspersed repeated DNA sequences of Chinese hamsters. Further DNA sequence comparisons demonstrate that a portion of this highly conserved segment of repetitive mamalian DNA sequence is similar to a sequence found within a low molecular weight RNA that hydrogen-bonds to poly(A)-terminated RNA molecules of Chinese hamsters and a sequence that forms half of a perfect inverted repeat near the origin of DNA replication in papovaviruses. PMID- 6246493 TI - Copper electron-nuclear double resonance of cytochrome c oxidase. AB - Electron-nuclear double resonance of copper was observed while monitoring the "intrinsic copper" electron paramagnetic resonance signal of cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1) near g = 2. This unambiguously establishes the presence of the metal (Cua) in the redox center responsible for this signal. The hyperfine couplings to copper are largely istropic and the maximum value is about half that seen in type I blue copper proteins. The magnetic properties of this oxidized copper center are not consistent with those of a thiyl radical (R-S) coordinated to Cu(I), and thus favor the identification of this redox center as a Cu(II) ion in a unique environment. PMID- 6246494 TI - Reactivation of ribosomal RNA genes in human-mouse hybrid cells by 12-O tetradecanoylphorbol 13-acetate. AB - The effect of the potent tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) on the expression of rRNA genes was studied in human greater than mouse hybrid cells (55-54 cells). These hybrids retain the rRNA genes of both parent species but express only human rRNA. 55-54 cells were treated with either TPA (1 100 nM), phorbol (0.01-1 micro M) or phorbol 13,20-diacetate (0.01-1 micro M). After 24 hr the cells were harvested and the extracted rRNA was analyzed by agarose/2.4% polyacrylamide gel electrophoresis. The results show that only the TPA-treated hybrid cells synthesized both human and mouse 28S rRNA. Untreated cells and cells treated with phorbol or phorbol 13,20-diacetate synthesized only human 28S rRNA. The reactivation of silent rRNA genes by TPA was not restricted to mouse rRNA genes. In mouse-human hybrids in which both human and mouse rRNA genes are present but only the mouse genes are expressed, TPA treatment led to reactivation of the silent human rRNA genes. Although tumor promoters are generally believed to alter gene expression, we have found a specific gene whose transcription is modified by treatment with TPA. PMID- 6246495 TI - Introduction of transposon Tn901 into a plasmid of Anacystis nidulans: preparation for cloning in cyanobacteria. AB - We have used the TEM beta-lactamase transposon Tn901, located on Escherichia coli plasmid pRI46, to introduce in vivo a genetic marker into plasmid pUH24, present in the cyanobacterial strain Anacystis nidulans R-2. Restriction enzyme analysis and heteroduplex studies of the 8.3 x 10(6)-dalton plasmids pCH1-pCH5, present in the ampicillin-resistant A. nidulans R-2 colonies obtained after transformation with pRI46, demonstrated that these plasmids consist of the complete sequence of Tn901 inserted at different places into plasmid pUH24. The pUH24::Tn901 recombinant plasmids transform A. nidulans R-2 with a frequency of 10(-4)--10(-5) per microgram of plasmid DNA and contain a single cleavage site for the restriction enzyme Xho I. From pCH1 a plasmid of 5.5 x 10(6) daltons,pUC1, was constructed with only a part of the Tn901 sequence and an additional single cleavage site for the restriction enzyme BamHI. This plasmid, as well as plasmids pCH1-pCH5, are potentially useful as vectors for cloning genes in cyanobacteria and for studying cyanobacterial plasmid biology. PMID- 6246497 TI - Comparative tryptic peptide mapping studies suggest a role in cell transformation for the gag-related protein of avian erythroblastosis virus and avian myelocytomatosis virus strains CMII and MC29. AB - The gag-related proteins found in cells transformed by avian erythroblastosis virus (AEV) and the avian myelocytomatosis viruses MC29 and CMII have been compared by tryptic peptide fingerprinting. A comparison of the methionine containing tryptic peptides of the AEV 75-kilodalton protein, the CMII 90 kilodalton protein, and the MC29 110-kilodalton protein with the gag gene product Pr76 of their naturally occurring helper leukemia viruses enabled us to distinguish those peptides related to the gag gene from the non-gag-related peptides. The 12 non-gag peptides found in the AEV 75-kilodalton protein were unique to this protein and not found in the MC29 110-kilodalton or CMII 90 kilodalton proteins. In contrast, the MC29 110-kilodalton protein shared two methionine-containing non-gag tryptic peptides with the CMII 90-kilodalton protein. When these experiments were repeated with [14C]lysine and [14C]arginine as the labeled amino acids, the MC29 110-kilodalton protein and the CMII 90 kilodalton protein were found to share 30 out of approximately 40 non-gag-related peptides. These results demonstrate that viruses with a similar transformation spectrum synthesize related proteins and suggest that the gag-related proteins represent the transforming proteins of the replication-defective avian leukemia viruses. PMID- 6246496 TI - Specificity of human antibodies to oncovirus glycoproteins: recognition of antigen by natural antibodies directed against carbohydrate structures. AB - Antibodies in human sera from healthy individuals were shown to be reactive with highly purified 70,000-dalton envelope glycoprotein (gp70) of the simian sarcoma virus-simian sarcoma-associated virus (SSV-SSAV) complex in radioimmunoprecipitation assays under certain conditions. The specificity of the reaction was analyzed in absorption tests with normal human serum proteins, assays of viral gp70 antigenicity after exposure to exo- and endoglycosidases or trypsin, and carbohydrate hapten inhibition studies. On the basis of the results obtained in these experiments we have concluded that immune recognition of SSV SSAV gp70 can be mediated by naturally occurring heterophil antibodies in human sera that are reactive by virtue of binding to the carbohydrate moiety of the viral gp70 molecules. The results are consistent with the idea that the antibodies in question are elicited as a result of exposure to many natural substances possessing widely crossreacting antigens and are not a result of widespread infection of man with replication-competent oncoviruses. PMID- 6246498 TI - Quantal release of acetylcholine examined by current fluctuation analysis at an identified neuro-neuronal synapse of Aplysia. AB - Quantal events have been analyzed at a neuro-neuronal synapse of Aplysia where the nature of the transmitter is established and both presynaptic and postsynaptic neurons are identified and can be voltage-clamped. Prolonged depolarizations were applied to the presynaptic neuron, which gave rise in the postsynaptic cell to a current response characterized by current fluctuations or noise. Acetylcholine was also applied ionophoretically on the same postsynaptic cell. Amplitude and time course of miniature currents and acetylcholine-activated chloride channels of the same cell were examined by using a current fluctuation analysis. It was estimated that one presynaptic spike releases about 180 quanta, each opening 500 chloride channels. PMID- 6246499 TI - Electrical excitability: a spectrum of properties in the progeny of a single embryonic neuroblast. AB - We have examined the range of some properties of the progeny of a single embryonic precursor cell in the grasshopper. The approximately 100 progeny of this single neuroblast share certain features such as their transmitter and some aspects of their morphology; at the same time, however, they demonstrate a broad spectrum of electrical properties, from spiking to non-spiking neurons. The first born progeny are spiking neurons with peripheral axons. Many of the progeny, including all of the last-born, do not generate action potentials. The nonspiking progeny are local intraganglionic neurons and appear to compose a major proportion of the progeny of this neuroblast. All of the nonspiking neurons have calcium inward current channels and can make action potentials when outward current channels are blocked. We propose a model for grasshopper neurogenesis based on cell lineage such that (i) certain features (e.g., transmitter) are shared by the progeny of all cell divisions from a single neuroblast, and (ii) other features (e.g., electrical properties) are shared by the progeny of a given birth position (e.g., first versus last born) from all of the neuroblasts. According to this model, the first-born progeny from all neuroblasts are spiking neurons, whereas the last-born are nonspiking. PMID- 6246500 TI - Probable precursors of [Leu]enkephalin and [Met]enkephalin in adrenal medulla: peptides of 3-5 kilodaltons. AB - Adrenal chromaffin granules contain at least 10 peptides, ranging in size from 3 to 5 kilodaltons, that yield, upon digestion with trypsin, peptides that show specific binding to opiate receptors. All are distinctly different from beta endorphin. Two of these peptides have been purified to homogeneity and subjected to chemical analysis. One is apparently a [Met]enkephalin precursor containing two copies of the [Met]enkephalin sequence. The other peptide contains both [Leu]enkephalin and [Met]enkephalin sequences and is presumably a common precursor of the two forms of enkephalin. PMID- 6246501 TI - Noradrenergic alpha 1 and alpha 2 receptors: light microscopic autoradiographic localization. AB - [3H]WB-4101 and p-[3H]aminoclonidine were used for light microscopic autoradiographic localization of alpha 1 and alpha 2 adrenergic receptors, respectively, in the rat brain. The binding of these ligands to slide-mounted tissue sections had all of the characteristics associated with alpha 1 and alpha 2 receptors. It was saturable with appropriate kinetic constants and was blocked only by other alpha-adrenergic drugs with the appropriate potency. Autoradiographic studies revealed a distribution of alpha-adrenergic receptors throughout the nervous system. Certain areas had elevated levels. These included parts of the olfactory bulb and nucleus, parts of the cerebral cortex and dentate gyrus, the more medial portions of the hypothalamus and thalamus, the locus ceruleus and nucleus tractus solitarii, and parts of the spinal cord. In certain areas, the distribution of alpha 1 and alpha 2 receptors was markedly different. These results provide some rational basis for the observed actions of alpha adrenergic drugs on the central nervous system. For example, the finding of high densities of alpha 2 receptors in the nucleus tractus solitarii is most likely related to its antihypertensive action. The observed codistribution of alpha 2 receptors with opiate receptors would provide an explanation of the observation that alpha 2 agonists block opiate withdrawal. The results are also discussed in relationship to the anatomy of catecholamine systems in the brain. PMID- 6246502 TI - Metabolite gene regulation of the L-arabinose operon in Escherichia coli with indoleacetic acid and other indole derivatives. AB - The ability of indole derivatives to facilitate RNA polymerase transcription of the L-arabinose operon in Escherichia coli was shown to require the catabolite activator protein (CAP) as well as the araC gene product. Adenosine 3',5' monophosphate (cAMP) was not obligatory for araBAD transcription when the cells were grown in the presence of 1 mM indole-3-acetic acid or in the presence of indole-3-acetamide, indole-3-propionic acid, indole-3-butyric acid, or 5 hydroxyindole-3-acetic acid. However, these indole derivatives were unable to circumvent the cAMP requirement for the induction of the lactose and the maltose operons. Catabolic repression occurred when glucose was added to cells grown in the presence of L-arabinose and 1 mM indoleacetic acid or 1 mM cAMP. This effect was reversed at higher concentrations of indoleacetic acid or cAMP. The induction and the catabolite repression phenomena were quantitated by measuring the differential rate of synthesis of L-arabinose isomerase (the araA gene product). These results indicated that indole metabolites from various living systems may regulate gene expression and may be involved in "metabolite gene regulation." PMID- 6246503 TI - Association of Mu-containing plasmids with the Escherichia coli chromosome upon prophage induction. AB - To determine the structure of a prophage-containing plasmid during Mu transposition, we have monitored the physical state of pSC101[unk]Mucts after thermoinduction. We have also examined the fate of a mini Mu plasmid constructed in vitro by deleting 27 kilobases from the center of the Mu prophage in pSC101[unk]Mucts. At various times after prophage induction, DNA was extracted from Mu or mini Mu plasmid-containing strains and subjected to electrophoresis in low concentration agarose gels followed by transfer of the DNA to nitrocellulose paper. Separate hybridization with (32)P-labeled pSC101 and Mu DNA revealed the position of the plasmids and the replication of Mu DNA. At times after induction when Mu replication was clearly visible, Mu and mini Mu plasmids were found to migrate with Escherchia coli DNA. This Mu-specific association requires the phage coded A and B proteins. Electron microscopy has shown that some of the associated DNA is comprised of circular plasmid molecules which appear to be in contact with the chromosomal DNA. These structures may represent intermediates or end products of the replication-integration process. The finding that Mu and mini Mu plasmids do not give rise to any detectable excision products and apparently remain intact during Mu transposition supports our proposal that the predominant event after Mu induction is the replication of Mu DNA in situ to generate integrative intermediates. PMID- 6246504 TI - Reconstitution of functional membrane-bound acetylcholine receptor from isolated Torpedo californica receptor protein and electroplax lipids. AB - Purified acetylcholine receptor and total lipids, both extracted from Torpedo californica electroplax, were utilized to reconstitute chemically excitable membrane vesicles. Reconstitution was achieved by dialysis of the extraction detergent, octyl beta-D-glucoside from protein/lipid incubation mixtures. The reconstituted preparations could be fractionated by sucrose density gradient centrifugation and consisted of vesicular structures visible in electron micrographs. In addition, the reconstituted vesicles exhibited;the following properties characteristic of native receptor-enriched membranes: (i) an external distribution of alpha-bungarotoxin-binding sites, (ii) a time-dependent binding of alpha-bungarotoxin that is depressed by preincubation with the cholinergic agonist carbamoylcholine ("desensitization"), (iii) an ability to retain 22Na+ that is lost in the presence of detergents or gramicidin A, and (iv) a carbamoylcholine-induced acceleration of 22Na+ efflux that can be blocked by alpha-bungarotoxin. The purified acetylcholine receptor that was utilized in the reconstitution experiments apparently does not require other protein components for ligand recognition or ion translocation. PMID- 6246505 TI - Cytochrome oxidase: an alternative model. AB - Oxidative titration of reduced cytochrome oxidase (cytochrome c oxidase; ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1) in the presence of carbon monoxide and sulfide, at potentials greater than +500 mV (vs. the neutral hydrogen electrode), have failed to produce new copper signals in the electron paramagnetic resonance spectrum of this enzyme. This observation implies that once of the copper centers in cytochrome oxidase remains Cu(I) under strongly oxidizing conditions. The rationalization of this fact, and the possible explanation of a great accumulation of spectroscopic data, is that cytochrome a3 may be a two-electron redox center, with stable Fe(IV), Fe(III), and Fe(II) states during its redox cycle. This oxidase model does not require an antiferromagnetic coupling scheme, in contrast to currently prevalent models. PMID- 6246506 TI - Direct measurement of bone resorption and calcium conservation during vitamin D deficiency or hypervitaminosis D. AB - When bone is remodeled during the growth of a given size bone to a larger size, some bone is resorbed and some is deposited. Much of the resorbed bone mineral, calcium, can be reutilized during bone formation. The net and absolute effects of normal growth, vitamin D deficiency, or vitamin D excess were compared on bone resorption, bone formation, and calcium reutilization. Growing chicks were prelabeled extensively with three isotopes: (45)Ca, [(3)H]tetracycline, and [(3)H]proline. Data were obtained weekly during 3 weeks of control growth, vitamin D deficiency, or vitamin D overdosage while on a nonradioactive diet. Bone resorption as measured by increases in the marrow (inner) diameter of the midshaft of the femur and humerus and by the weekly losses of total [(3)H]tetracycline and [(3)H]collagen per whole bone was not significantly different among any of the groups studied. The data indicated that the high rate of cortical bone resorption in experimental chicks was not increased above that observed in experimental chicks was not increased above that observed in control chicks. Vitamin D deficiency had little effect on the total (45)Ca in whole bones, whereas vitamin D-treated chicks lost 40% of their (45)Ca. Thus, vitamin D overdosage resulted in a decrease of (45)Ca reutilization, whereas vitamin D deficiency resulted in an apparent increase of (45)Ca reutilization. Both vitamin D-deficient and vitamin D-treated chicks had a decreased accumulation of dietary calcium per whole bone. The insufficient mineral mass in vitamin D-deficient chicks resulted from the indirect inhibition of bone mineralization due to the low intestinal absorption of calcium rather than from a change in bone resorption. In vitamin D-treated chicks the apparent bone atrophy and net loss of (45)Ca from bone resulted from inhibiting bone matrix formation and mineralization instead of increasing bone resorption. The constancy of bone resorption under these experimental conditions suggests that bone mineralization is the major regulator of bone mass. PMID- 6246507 TI - Isolation, characterization, and comparison of recombinant DNAs derived from genomes of human hepatitis B virus and woodchuck hepatitis virus. AB - The human hepatitis B virus (HBV) and the woodchuck hepatitis virus (WHV) are closely related by several criteria and belong to the same class of DNA viruses. The DNA genomes from these viruses are difficult to obtain in quantities required for biochemical analysis. We have, therefore, cloned these two DNAs in the vector lambda gtWES and subcloned into the kanamycin resistance plasmid pA01. Comparison of the recombinant DNAs with authentic viral DNAs by specific hybridization, size, and restriction enzyme analysis suggests that the recombinants contain the complete genome of each virus. The nominal size of the cloned HBV genome was 3150 base pairs, compared to 3200 base pairs for the cloned WHV genome. The small amount of nucleic acid homology previously reported between the HBV and WHV DNAs could be demonstrated between the cloned viral DNAs. PMID- 6246508 TI - DNA gyrase action involves the introduction of transient double-strand breaks into DNA. AB - DNA gyrase from Escherichia coli, in the presence of ATP, can both separate catenated DNA circles and unknot knotted DNA. Both these reactions require passage of a DNA segment through a transient double-strand break in DNA. Evidence that transient double-strand breaks are also involved in the supercoiling and relaxing activities of DNA gyrase is derived from experiments showing that the linking number of circular DNA is changed in steps of two. A mechanism is proposed for the action of the enzyme. PMID- 6246509 TI - Mapping of the two overlapping genes for polypeptides NS1 and NS2 on RNA segment 8 of influenza virus genome. AB - RNA segment 8 of the influenza virus genome is unique in coding for two polypeptides, NS1 (Mr, approximately 25,000) and NS2 (Mr, approximately 11,000). These polypeptides are synthesized from separate mRNA species. By using cloned DNA derived from RNA segment 8 (NS DNA) the two mRNAs have been mapped on segment 8 by hybridization of mRNAs with restriction endonuclease fragments of the DNA and nuclease S1 digestion methods. These data indicate that the body of the NS1 mRNA (approximately 850 nucleotides) maps at 0.05-0.95 units of the cloned NS DNA and the body of the NS2 mRNA (approximately 340 nucleotides) maps at 0.59-0.95 unitssuggesting that the two mRNAs are 3' coterminal and share the same poly(A) addition site. These positions of the mRNAs on the viral genome segment were confirmed in hybrid-arrested translation experiments using fragments of the cloned NS DNA to inhibit the synthesis in vitro of NS1 or NS2 polypeptides. In addition, in these translation experiments the use of certain DNA fragments resulted in premature termination of the NS1 polypeptide. From these data, it could be estimated that the termination of translation of NS1 is at approximately 0.76 map unit. Thus, the coding regions of the two mRNAs overlap by approximately 144-159 nucleotides, the equivalent of approximately 48-53 amino acids. Peptide mapping experiments indicated that polypeptides NS1 and NS2 do not share methionine- or leucine-containing tryptic peptides. The results obtained indicate the translation of the NS2 mRNA occurs in a reading frame different from that used for NS1. PMID- 6246510 TI - Translocation of phospholipids from the inner to the outer membrane of Escherichia coli. AB - The translocation of lipids from the inner to the outer membrane of Escherichia coli has been investigated by pulse-chase experiments. After a pulse with [2 3H]glycerol, the specific activity of the newly synthesized [3H]phosphatidylethanolamine was 5 times greater in the inner than in the outer membrane. During the chase, [3H]phosphatidylethanolamine was translocated to the outer membrane. At 37 degrees C, the half-life for translocation was 2.8 min. This rate was not influenced by alteration in the cellular growth rate at 37 degrees C. Altering the cellular growth temperature had a pronounced effect on the rate of phosphatidylethanolamine translocation. Energy inhibitors that deplete the protonmotive force markedly inhibited the translocation. Translocation was not affected by inhibitors of ATP, protein, or lipid synthesis. Phosphatidylglycerol and cardiolipin are transfocated very rapidly, with half lives shorter than 30 sec. PMID- 6246511 TI - A mechanism for RNA splicing. AB - The most abundant of the stable small nuclear RNAs of eukaryotic cells, U-1 small nuclear RNA, is exactly complementary to the consensus sequences at RNA splice sites. We propose that this RNA is the recognition component of the nuclear RNA splicing enzyme and forms base pairs with both ends of an intron so as to align them for cutting and splicing. PMID- 6246512 TI - Protein synthetic errors do not increase during aging of cultured human fibroblasts. AB - To test the error catastrophe theory of aging we determined the error frequency of protein synthesis in several strains of cultured human fibroblasts at early and late passage. Error rates were calculated from analysis of native and substituted actins on two-dimensional gels of cellular proteins after induction of mistranslation by histidine starvation in the presence of histidinol. Early passage cells from fetal, young, and old donors and cells from subjects with the Hutchinson-Gilford and Werner syndromes of accelerated aging had similar error frequencies. Late-passage cells from fetal, young, and old normal donors had similar or lower error frequencies than corresponding early-passage cells. No correlation was observed between error frequency, donor age, or maximal life span in vitro. We also examined an immortal cell line, simian virus 40-transformed W138 fibroblasts. These cells had a significantly elevated rate of mistranslation (2.8 +/- 0.2 x 10(-4))(+/- SEM) compared to their untransformed counterpart WI38 (0.6 +/- 0.1 X 10(-4)) or all diploid cells combined (1.1 +/- 0.1 x 10(-4)). Taken together, the data fail to support the error catastrophe theory of aging. PMID- 6246513 TI - Yeast mating pheromone alpha factor inhibits adenylate cyclase. AB - The pheromone alpha factor, secreted by Saccharomyces cerevisiae cells of the alpha mating type, serves to synchronize the opposite mating type (a cells) at G1 as a prelude to fusion of the two cell types. We found that, in vitro, alpha factor inhibited the membrane-bound adenylate cyclase of these cells in a dose dependent manner. Moreover, one class (ste5) of a cell mutants that grow normally at either 23 degrees or 34 degrees C but that are unable to respond to alpha factor or to mate at the higher temperature possessed an adenylate cyclase activity that was not inhibited by alpha factor at 34 degrees C but was fully sensitive to inhibition at 23 degrees C. Furthermore, addition of cyclic AMP to a cell culture medium shortened the period of pheromone-induced G1 arrest. We conclude that inhibition of adenylate cyclase activity by alpha factor may constitute, at least in part, the biochemical mode of action of the pheromone in vivo. PMID- 6246514 TI - Pyrophosphate:protein phosphotransferase: a membrane-bound enzyme of endoplasmic reticulum. AB - Recently, we demonstrated that highly purified rat liver microsomal membrane was capable of selectively phosphorylating two intrinsic membrane polypeptides (M(r) 145,000 and M(r) 130,000) and that the course of the reaction was kinetically divided into two distinct stages [Lam, K. S. & Kasper, C. B. (1980) J. Biol. Chem. 255, 259-266]. Evidence was also presented that strongly suggested that a phosphoryl donor other than ATP was involved in the second stage of phosphorylation. In the present study, we demonstrate that incubation of microsomal membrane with [gamma-(32)P]ATP produces a prominent (32)P-labeled compound detectable by thin-layer chromatography on polyethyleneimine-impregnated cellulose. DEAE-cellulose fractionation of detergent-solubilized microsomal membrane generated a protein fraction that could convert in excess of 90% of the [gamma-(32)P]ATP into this newly (32)P-labeled unknown compound (I approximately P) without the formation of significant levels of (32)P(i). When [alpha-(32)P]ATP was used, I approximately P was unlabeled. Enzymically synthesized I approximately P was purified and determined to be pyrophosphate by using (31)P NMR spectroscopy. [(32)P]Pyrophosphate, synthesized chemically or enzymically, was capable of selectively phosphorylating the M(r) 145,000 and M(r) 130,000 polypeptides. Time course studies utilizing pyrophosphate as the phosphate source showed only one phase of phosphorylation that was strongly inhibited by micromolar levels of ATP as well as by NaF (5 mM). These studies further establish that pyrophosphate is the phosphoryl donor involved in the second stage of phosphorylation. PMID- 6246515 TI - Sendai virus receptor: proposed recognition structure based on binding to plastic adsorbed gangliosides. AB - The binding of Sendai virus to polystyrene petri dishes to which various gangliosides of defined structures had been adsorbed was determined. The ganglioside-bound virus was visualized either by a water vapor condensation method or by a hemadsorption method. By either assay, specific virus binding of high affinity was demonstrated to the gangliosides GT1a, GQ1b, and GPlc which have a common end sequence in the oligosaccharide moiety: NeuAc alpha 2 leads to 8NeuAc alpha 2 leads to 3Gal beta 1 leads to 3GalNAc leads to. Binding also occurred to the GD1a and GT1b gangliosides, which have the same end carbohydrate sequence except for the terminal N-acetylneuraminic acid, but the affinity was only 1-9% of that of the gangliosides with a terminal disialosyl linkage. It is proposed that the structure NeuAc alpha 2 leads to 8NeuAc alpha 2 leads to 3Gal beta 1 leads to 3GalNAc is the recognition-specific structure of the receptor for Sendai virus that is present on cell membrane gangliosides and possibly also glycoproteins. Binding tests to plastic-adsorbed glycolipids are suggested to be a useful tool for identification of the receptor recognition structure. PMID- 6246516 TI - On reagents that convert cytochrome oxidase from an inactive to an active coupling state. AB - Cytochrome oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1) of beef heart mitochondria, prepared by a standard method and brought to the highest purity level, is essentially inactive when tested in the aerobic assay involving oxidation of reduced cytochrome c by molecular oxygen. Three reagents (lysolecithin, Tween 20, and exogenous phospholipids) can convert cytochrome oxidase from an inactive to an active coupling state. These conversions are reversible: i.e., removal of the inducing agent leads to loss of activity. The evidence for the intrinsic coupling capability is that cytochrome oxidase in the active state invariably generates a proton gradient during respiration, and such gradient formation is demonstrable even when cytochrome oxidase is not inserted into a liposome. PMID- 6246517 TI - DNA alkylation and unwinding induced by benzo[a]pyrene diol epoxide: modulation by ionic strength and superhelicity. AB - Superhelical and partially relaxed DNAs of simian virus 40 were allowed to react in vitro with (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10 tetrahydrobenzo[a]pyrene (BaP diol epoxide). The modified DNA contained N2 guanine and N6 adenine hydrocarbon adducts in the ratio 86:14. Superhelical simian virus 40 DNA was approximately 6% more susceptible to modification than was partially relaxed viral DNA. Counterions inhibited DNA alkylation by up to 90%, Mg2+ being 50-fold more effective than Na+. The sensitivity of covalent binding to helix stability is consistent with a reaction complex in which BaP diol epoxide is intercalated. The superhelical density of the modified DNA substrates was determined electrophoretically relative to partially relaxed standards, and an unwinding angle for the hydrocarbon adducts was calculated. The angle was dependent upon the superhelicity of the DNA molecule and ranged from 330 degrees to 30 degrees. These data indicate that the modified base pairs are disrupted and, in the presence of torsional strain, act as centers for the further denaturation of up to eight adjacent base pairs. In the absence of such strain the alkylation sites have an ordered structure, with the attached hydrocarbon probably oriented in the minor or major groove of the helix. PMID- 6246518 TI - Fujinami sarcoma virus: an avian RNA tumor virus with a unique transforming gene. AB - The oncogenic properties and RNA of the Fujinami avian sarcoma virus (FSV) and the protein it encodes were investigated and compared to those of other avian tumor viruses with sarcomagenic properties such as Rous sarcoma virus and the acute leukemia viruses MC29 and erythroblastosis virus. Cloned stocks of FSV caused sarcomas in all chickens inoculated and were found to contain a 4.5 kilobase (kb) and an 8.5-kb RNA species. The 4.5-kb RNA was identified as the genome of defective FSV because it was absent from nondefective FSV-associated helper virus and because the titer of focus-forming units increased with the ratio of 4.5-kb to 8.5-kb RNA in virus preparations. This is, then, the smallest known tumor virus RNA with a transforming function. Comparisons with other viral RNAs, based on oligonucleotide mapping and molecular hybridization, indicated that 4.5-kb FSV RNA contains a 5' gag gene-related sequence of 1 kb, an internal specific sequence of about 3 kb that is unrelated to Rous sarcoma virus, MC29, and erythroblastosis virus, and a 3'-terminal sequence of about 0.5 kb related to the conserved C region of avian tumor viruses. The lack of some or all nucleotide sequences of the essential virion genes, gag, pol, and env, and the isolation of FSV-transformed nonproducer cell clones indicated that FSV is replication defective. A 140,000-dalton, gag-related non-structural protein was found in FSV transformed producer and nonproducer cells and was translated in vitro from full length FSV RNA. This protein is expected to have a transforming function both because its intracellular concentration showed a positive correlation with the percentage of transformed cells in a culture and because FSV is unlikely to code for major additional proteins since the genetic complexities of FSV RNA and the FSV protein are almost the same. It is concluded that the transforming onc gene of FSV is distinct from that of Rous sarcoma virus and other avian tumor viruses with sarcomagenic properties. Hence, multiple mechanisms exist for sarcomagenic transformation of avian cells. PMID- 6246519 TI - Net proton-hydroxyl permeability of large unilamellar liposomes measured by an acid-base titration technique. AB - The net proton-hydroxyl permeability of large unilamellar liposomes has been measured by an acid-base pulse titration technique and has been determined to be several orders of magnitude greater than that measured for other monovalent ions. This permeability is relatively insensitive to variations in lipid composition. Proton permeability and hydroxyl permeability vary with pH 6 to 8, and this variation can occur in the absence of alterations in surface charge density resulting from titrations of acidic and basic groups on the lipids. In order to account for the exceptionally high proton-hydroxyl permeability with respect to other monovalent ions, we propose that protons or hydroxyls or both interact with clusters of hydrogen-bonded water molecules in the lipid bilayer, such that they are transferred across the bilayer by rearrangement of hydrogen bonds in a manner similar to their transport in water and ice. PMID- 6246520 TI - Relationship of polypeptide products of the transforming gene of Rous sarcoma virus and the homologous gene of vertebrates. AB - All vertebrate cells have been shown to contain a gene, sarc, that has some homology with the transforming gene of Rous sarcoma virus, src. We have compared the polypeptide products of the sarc gene, p60(sarc), of human, mouse, and chicken cells with the polymorphic polypeptide product of the src gene, p60(src), of several strains of Rous sarcoma virus by two-dimensional peptide mapping. p60(sarc) from chicken cells was clearly related to every viral p60(src). Eleven of its 13 methionine-containing tryptic peptides were present in some viral p60(src). Conversely, the other two peptides were not present in any p60(src) we have examined so far. The 11 peptides from p60(sarc) of chickens that were shared with viral p60(src), however, were not all present in any single viral p60(src). These 11 peptides most closely resemble those in the p60(src)s of B77 virus and the Prague strain of Rous sarcoma virus. These data are consistent with the hypothesis that cellular sarc is the progenitor of viral src. The p60(sarc)s of human, mouse, and chicken cells were so similar in tryptic peptide composition that they were more closely related to each other than were some viral p60(src)s. The two mammalian p60(sarc)s differed from avian p60(sarc) most notably in that they lacked a peptide that chicken p60(sarc) shares with all the viral p60(src)s. The similarity of these maps suggests that the sequence of the p60(sarc) polypeptide has diverged very little during evolution. This may imply that p60(sarc) is an essential cellular component. PMID- 6246521 TI - Interaction of cholecystokinin with specific membrane receptors on pancreatic acinar cells. AB - We have prepared (125)I-labeled cholecystokinin and have examined the kinetics, stoichiometry, and chemical specificity with which the labeled peptide binds to dispersed acini from guinea pig pancreas. Binding of (125)I-labeled cholecystokinin was reversible, temperature-dependent, saturable, specific, and localized to the plasma membrane. Each acinar cell possessed approximately 9000 binding sites, and binding of the labeled peptide to these sites could be inhibited by cholecystokinin and structurally related peptides (e.g., gastrin and caerulein) as well as by nonpeptide competitive antagonists of the action of cholecystokinin. Binding was not inhibited by other pancreatic secretagogues such as secretin, vasoactive intestinal peptide, glucagon, physalaemin, eledoisin, kassinin, substance P, carbamoylcholine, litorin, or ranatensin or by bovine pancreatic polypeptide, atropine, neurotensin, leucineenkephalin, methionine enkephalin, or cyclic somatostatin. With agonists as well as antagonists there was a good correlation between occupation of cholecystokinin binding sites and changes in acinar cell function. With each of six different peptide agonists maximal stimulation of enzyme secretion occurred with 40% receptor occupation and occupation of the remaining 60% caused a progressive decrease in stimulated amylase release. Agonists, but not antagonists, accelerated the dissociation of bound (125)I-labeled cholecystokinin, and these findings suggest that, in pancreatic acini, radiolabeled cholecystokinin binds to at least one class of interacting binding sites whose affinities are influenced by the extent to which these sites are occupied by agonists but not the extent to which they are occupied by antagonists. PMID- 6246522 TI - Introduction of a viral thymidine kinase gene and the human beta-globin gene into developmentally multipotential mouse teratocarcinoma cells. AB - Teratocarcinoma (TCC) stem cells provide unique prospects for the introduction of specific genes into mice, by virtue of their dual capacity for propagation in vitro and for normal differentiation in embryos. In this study, we have demonstrated that foreign genes amenable to selection in culture can be transferred into the stem cells and expressed. These cells maintain expression of the gene for long periods during differentiation in tumors in vivo in the absence of selective pressure. The cells also integrate an unlinked nonselectable gene at high frequency. Addition of the cloned herpes simplex virus (HSV) thymidine kinase (tk; ATP:thymidine 5'-phosphotransferase, EC 2.7.1.21) gene to cultures of tk(-)TCC cells yielded tk(+) colonies at a frequency of one colony per 4 mug of plasmid DNA. This transformation efficiency, although appreciably lower than for mouse L tk(-) cells, permits the isolation of many transformants. The HSV provenance of the transformed phenotype was verified by the characteristic electrophoretic mobility of the tk protein and by neutralization of the tk activity with specific antiserum. Moreover, blot hybridization tests revealed at least one intact copy of the viral tk gene integrated into the DNA of transformed cells. When injected into syngeneic mice, the cells formed solid tumors with various differentiating tissues. From blot hybridization comparisons with their cell lines of origin, seven of nine tumors examined had maintained the HSV tk gene without significant loss or rearrangement. Viral tk enzyme activity could also be demonstrated in at least some of the tumors. Cotransfer of the cloned human beta-globin gene along with the unlinked HSV tk gene was successful in 2 of 10 tk(+) transformants. Thus, defined genes can be stably introduced into TCC cells in culture and maintained in vivo in a form in which they are transcribed and translated to produce a functional protein. PMID- 6246523 TI - Isolation of genes by complementation in yeast: molecular cloning of a cell-cycle gene. AB - cdc28, one of several genes required for cell division in the yeast Saccharomyces cerevisiae, has been isolated on recombinant plasmids. A recombinant plasmid pool containing the entire yeast genome was constructed by partial digestion of yeast DNA with the four-base recognition restriction endonuclease Sau3A to give the equivalent of random fragments, size selection on sucrose gradients, and introduction of the fragments into the yeast vector YRp7 by use of the homology of Sau3A ends with those generated in the vector by cleavage with BamHI. Recombinant plasmids capable of complementing cdc28 mutations were isolated by transformation of a cdc28ts strain and selection for clones capable of growth at the restrictive temperature. Plasmids responsible for complementing the cdc28ts phenotype were shown to recombine specifically with the chromosomal cdc28 locus, confirming the identity of the cloned sequences. In addition, one of the recombinant plasmids was capable of complementing a mutation in tyr1, a gene genetically linked to cdc28. This method of gene isolation and identification should be applicable to all yeast genes for which there are readily scorable mutants. PMID- 6246524 TI - DNA sequence of baboon highly repeated DNA: evidence for evolution by nonrandom unequal crossovers. AB - A highly repeated DNA was isolated from the West African baboon (Papio papio) as a 343-base-pair fragment after digestion of total baboon DNA with the restriction endonuclease BamHI. The DNA sequence of this fragment was obtained by chemical cleavage methods and is compared with the DNA sequence of related highly repeated primate DNAs from African green monkey (Cercopithecus aethiops) and man. The 343 base-pair baboon repeat consists of two related but nonidentical wings of 172 and 171 base pairs, respectively. The baboon 172-base-pair wing shares more homology with the African green monkey 172-base-pair repeat than with the baboon 171-base pair wing. Comparison with the previously published monkey and human DNA sequences indicates that: (i) All the DNA sequences apparently arose from a common ancestral sequence. (ii) Evolution of the primate DNA sequences can be explained by a model involving unequal crossovers at specific points within the repeated DNA, possibly mediated by the sequence 5'-AAGG-3' 3'-TTCC-5' or its invert 5'-GGAA-3' 3'-CCTT-5'. (iii) There are alternating domains of conserved and divergent DNA sequences within each greater than 170-base-pair wing sequence. Taken together, the DNA sequences of these primates suggest a model whereby highly repeated DNAs are established and evolve as a consequence of unequal nonrandom exchanges of DNA duplexes. These exchanges may be mediated by short repeated nucleotide sequences and involve exchanges within and between the greater than 170-base-pair wings. PMID- 6246525 TI - Direct transfer of cloned genes from bacteria to mammalian cells. AB - Induction of a virus infection by cloned simian virus 40 DNA was chosen as a test system to detect transfer of genes from bacteria to cultured mammalian cells. Escherichia coli cells containing a recombinant plasmid with three tandem inserts of simian virus 40 DNA were able to infect CV-1 monkey cells under various conditions. The gene transfer was resistant to DNase I and therefore seems not to occur via free DNA but most likely via uptake of whole bacteria, followed by release of plasmid DNA and generation of infectious circular simian virus 40 DNA in a recombination-excision process. Spontaneous transfer was found to be infrequent, 4 x 10(9) bacteria yielding one infection per 10(7) monkey cells. The frequency was greatly increased by adding bacteria as a calcium phosphate coprecipitate or by fusion of lysozyme-treated bacteria (protoplasts) with monkey cells in the presence of polyethylene glycol. With the latter technique, 10(4) protoplasts gave rise to one infection per 15 monkey cells. Experiments with other cell lines of human, monkey, and mouse origin, and also with bacteria harboring another recombinant plasmid, indicate that DNA transfer from bacteria to mammalian cells is a general phenomenon. PMID- 6246526 TI - In vitro production of immunosuppressive factors by murine sarcoma virus transformed mouse fibroblasts. AB - Murine sarcoma virus-transformed mouse fibroblasts produce potent immunosuppressive factors (ISF) in vitro. The partially purified ISF inhibited thymocyte proliferation induced by concanavalin A or phytohemagglutinin plus lymphocyte activating factor (Interleukin 1), lipopolysaccharide-induced spleen cell proliferation, the in vitro splenic anti-sheep erythrocyte plaque-forming cell response, and the generation of alloantigen-specific cytotoxic T cells. The effect of ISF on thymocyte proliferation was not readily reversible and required only a 4-hr exposure of the thymocytes to ISF to inhibit cell proliferation. Although ISF shares several biochemical properties with a murine sarcoma virus transformed cell-derived sarcoma growth factor (e.g., acetic acid solubility and sensitivity to dithiothreitol), the two factors could be resolved by gel filtration on Bio-Gel P-60. Two peaks of ISF activity were found with apparent molecular weights of 12,000 and 8000. The results described here support the hypothesis that at least some of the ISF obtained from the serum of tumor-bearing hosts may be released by the tumor cells themselves. In view of the potent in vitro activity of the murine sarcoma virus-transformed fibroblast-derived ISF, it is quite possible that ISF-like molecules may play a role in subverting in vivo tumor rejection processes involving the immune system. PMID- 6246527 TI - Protease-activated "prodrugs" for cancer chemotherapy. AB - Many types of malignant cells and human tumors display increased concentrations of the protease plasminogen activator that converts plasminogen to the highly active protease, plasmin. Because plasmin rapidly cleaves various low molecular weight compounds coupled to appropriate peptide specifiers, we hypothesized that coupling of such peptide specifiers to anticancer drugs might create "prodrugs" which would be locally activated by tumor-associated plasmin and consequently would be less toxic to normal cells. To provide an initial test of this concept we have synthesized peptidyl prodrugs of the structure D-Val-Leu-Lys-X in which the peptidyl portion has been designed to allow the prodrug to serve as an excellent plasmin substrate and X is an anticancer drug-either the glutamine analog (alphaS,5S) alpha-amino-3-chloro-4,5-dihydro-5-isoxazole-acetic acid (AT 125) or the alkylating agent N,N-bis(2-chloroethyl)-p-phenylenediamine (phenylenediamine mustard). Treatment of these prodrugs with plasmin generated the free peptide and the free drug, demonstrating that these prodrugs are plasmin substrates. The prodrugs and free drugs were tested in an in vitro system against either normal chicken embryo fibroblasts, which display a low level of plasminogen activator, or their virally transformed counterparts, which produce high levels of plasminogen activator. In each case the peptidyl prodrugs displayed at least a 5-fold increase in selectivity for the transformed cells compared to the free drug. The greater selectivity of action of the peptidyl prodrugs against transformed cell cultures suggests that these or similar prodrugs that are substrates for tumor-associated proteases may show increased therapeutic effectiveness in the treatment of tumors that produce sufficiently increased amounts of plasminogen activator. PMID- 6246529 TI - Expression of peanut agglutinin receptors on virus-induced preleukemic cells in mice. AB - Preleukemic bone marrow and spleen cells of irradiated C57BL/6 mice that were inoculated with the radiation-induced leukemia virus variant D-RadLV differ from autonomous end-stage leukemia cells in the expression of the receptor for peanut agglutinin. As a result, the preleukemic cells are agglutinated by peanut agglutinin and the end-stage cells are not. This observation provides further evidence that preleukemic cells possess surface markers similar to those of the prothymocyte. In vitro and in vivo thymocyte-virus interactions reveal that cells susceptible to D-RadLV transformation are present mainly among the peanut agglutinin-receptor-bearing thymocyte population which has previously been demonstrated to be immunologically immature. PMID- 6246528 TI - Adrenocortical response to corticotropin is potentiated by part of the amino terminal region of pro-corticotropin/endorphin. AB - Five peptides derived from pro-corticotropin/endorphin (pro-ACTH/endorphin), the pituitary corticotroph cell prohormone, were bioassayed with isolated rat adrenocortical cells: alpha- and beta-melanotropin, beta-lipotropin, beta endorphin, and the amino-terminal region of pro-ACTH/endorphin known as "16k fragment." The effect of each on steroidogenesis was measured at potentially physiological concentrations (0.01-1 nM) in both the absence and presence of varying concentrations of ACTH-(1-24). Of the peptides tested, only 16k fragment, the amino-terminal region of pro-ACTH/endorphin, has a slight but significant potentiating effect on ACTH-(1-24) action. Prior treatment of 16k fragment with trypsin for 30 sec dramatically increases this dose-dependent synergism. Experiments performed in vivo with hypophysectomized female rats indicate that the trypsin digest of 16k fragment stimulates cholesterol ester hydrolase (cholesterol esterase; sterol-ester acylhydrolase, EC 3.1.1.13) activity in the adrenal cortex but fails to activate cholesterol side-chain cleavage. The effect of the trypsinized material can therefore be qualitatively distinguished from that of ACTH-(1-24). When both ACTH-(1-24) and the digest are administered together, a synergistic increase in serum corticosterone concentration results. We propose that a portion of 16k fragment molecule may play a hormonal role in the control of adrenocortical steroidogenesis. PMID- 6246530 TI - Highly efficient induction of type C retroviruses by a human tumor in athymic mice. AB - We have found that 1 of 20 human tumors transplanted and passaged in nude mice was associated with a massive induction of endogenous murine leukemia virus (MuLV). Separation and growth of these viruses on various substrates indicated that both ecotropic and xenotropic MuLV were present in the induced mixture. Tryptic peptide fingerprints of the p30 and gp70 structural elements of the viruses indicated that all of the known endogenous muLVs of BALB/c mice were present in the mixture. In addition, a new xenotropic MuLV was identified. The human tumor that induced the viruses was an oat cell carcinoma. The oat cell carcinoma possibly produced a specific hormone or factor that acts as a potent inducer of endogenous type C retroviruses. PMID- 6246531 TI - Two distinct loci confer resistance to acycloguanosine in herpes simplex virus type 1. AB - Two distinct loci that confer resistance to acycloguanosine (acyclo-Guo) in herpes simplex virus types 1 have been identified. The first locus is the gene for the virus-specific thymidine kinase (TK). Mutations that decrease TK activity also render the virus resistant to acyclo-Guo, and the level of resistance corresponds to the decrease in TK activity. acyclo-Guo resistance due to defective TK expression is recessive to the wild-type phenotype, acyclo-Guo sensitive (ACGs). We term this locus ACGr-TK. The second locus is defined by the properties of a mutant, PAAr5, which is resistant to acyclo-Guo and to phosphonoacetic acid (PAA) yet exhibits wild-type TK activity. The acyclo-Guo resistant locus in PAAr5 is separable from ACGr-TK mutations by recombination. Moreover, PAAr5 and ACGr-TK mutants can complement each other, producing drug sensitive gene products which result in growth inhibition in the presence of acyclo-Guo. The acyclo-Guo resistance conferred by PAAr5 behaves as though it were codominant with the wild-type phenotype. This second acyclo-Guo-resistance locus is closely linked to the mutation specifying resistance to PAA. Resistance to PAA is thought to result from mutations in the gene for viral DNA polymerase. Thus, the close linkage of the ACGr and PAAr loci suggest that resistance to both drugs is specified by a mutant DNA polymerase. We term this second locus ACGr PAA. PMID- 6246532 TI - Resistance of herpes simplex virus to acycloguanosine: role of viral thymidine kinase and DNA polymerase loci. AB - Acycloguanosine [9-(2-hydroxyethoxymethyl)guanine; acyclo-Guo] is a potent inhibitor of herpes simplex viruses (HSV); it is selectively phosphorylated in virus-infected cells. In order to define those viral functions that may mediate resistance to acyclo-Guo, the drug sensitivities of temperature-sensitive (ts) and phosphonoacetic acetic acid (PAA)-resistant mutants of HSV-1 and HSV-2 have been determined. Two distinct viral genetic loci are independently associated with acyclo-Guo resistance. Mutations resulting in diminished thymidine kinase activity are associated with resistance to inhibition by acyclo-Guo. Several PAA resistant viruses that express wild-type levels of thymidine kinase activity are also resistant to acyclo-Guo. This suggests the importance of the viral DNA polymerase region in mediating acyclo-Guo resistance and is consistent with a close relationship between the PAAr mutation site and the AGGr locus. When wild type HSV-1 is serially propagated under the selective pressure of acyclo-Guo, rapid emergence of resistant virus occurs, accompanied by the simultaneous appearance of thymidine kinase-deficient progeny. PMID- 6246533 TI - Two tumor antigens and their polypeptides in adenovirus type 12-infected and transformed cells. AB - A tumor (T) antigen, designated T antigen g, was visualized as fine fluorescent granules in nuclei of adenovirus type 12 (Ad12)-infected cells by immunofluorescence with sera from rats bearing HY cell tumors (H sera). HY cells are rat cells incompletely transformed by the Acc I-H endonuclease fragment (0 4.7 map units) of Ad12 DNA. The antigen is different from the usually described T antigen, designated T antigen f, which is visualized as fluorescent flecks or filaments in both nucleus and cytoplasm of Ad12-infected cells when tested with narrowly reacting T sera. Extracts of [(35)S]methioninelabeled infected cells were immunoprecipitated with H sera, and the resultant precipitate was analyzed by the two-dimensional gel electrophoresis technique of O'Farrell. The autoradiogram showed the presence of a cluster of several polypeptides (M(r) 35,000-40,000, pI 5.0-5.5) that was absent in extracts of mock-infected cells. A similar autoradiogram of infected cells analyzed with narrowly reacting T sera showed the presence of a small polypeptide (M(r) 10,000, pI 6.4), that was absent in extracts of mock-infected cells. The results show that M(r) 35,000-40,000 polypeptides are components of T antigen g and a M(r) 10,000 polypeptide is a component of T antigen f. Ad12-transformed cells showed a similar result. T antigen g was present and T antigen f was absent in HY cells. Both T antigen g and T antigen f were present in CY cells, which are rat cells completely transformed by the EcoRI-C endonuclease fragment (0-16 map units) of Ad12 DNA. The possible functions of these proteins are discussed. PMID- 6246534 TI - Tumorigenic transformation induced by a specific fragment of DNA from herpes simplex virus type 2. AB - Transfection of Syrian hamster embryo cells with limit digests of Bgl II-, Hpa I , or Bgl II/Hpa I-cleaved DNA from herpes simplex virus type 2 (strain S-1) but not with salmon sperm DNA resulted in the appearance of refractile, morphologically altered cells at a frequency of 10(-5)/0.005 microgram of viral DNA within two to four passages. Transformed lines manifested reduced serum requirement and anchorage-independent growth and were tumorigenic in newborn hamsters. They expressed ICP10, a viral protein immunologically identical to the cervical-tumor-associated AG-4 antigen. Transforming activity was localized in the 16.5 x 10(6)-dalton Bgl II/Hpa I double-digest fragment CDs-1, which exhibited sequence homology to the Bgl II/Hpa I fragment CD of DNA from herpes simplex virus type 2 strain 333, mapping between coordinates 0.43 and 0.58 on the physical map of strain 333 DNA. This fragment, CD333, was also shown to induce neoplastic transformation. PMID- 6246535 TI - Urinary and brain beta-carboline-3-carboxylates as potent inhibitors of brain benzodiazepine receptors. AB - Benzodiazepines probably exert their anxiolytic, hypnotic, and anticonvulsant effects by interacting with brain-specific high-affinity benzodiazepine receptors. In searching for possible endogenous ligands for these receptors we have purified a compound 10(7)-fold from human urine by extractions, treatment with hot ethanol, and column chromatography. The compound was identified as beta carboline-3-carboxylic acid ethyl ester (IIc) by mass spectrometry, NMR spectrometry, and synthesis; IIc was also isolated from brain tissues (20 ng/g) by similar procedures. Very small concentrations of IIc displaced [3H]diazepam completely from specific cerebral receptors, but not from liver and kidney binding sites; the concentration causing 50% inhibition of specific [3H]diazepam binding (IC50) was 4-7 nM compared to ca. 5 nM for the potent benzodiazepine lorazepam. Specific binding sites for quinuclidinyl benzilate, naloxone, spiroperidol, serotonin, muscimol, and WB 4101 were not affected by IIc. In contrast to benzodiazepines, IIc exhibits "mixed type" competitive inhibition of forebrain benzodiazepine receptors (negative cooperativity). We surmise that an endogenous ligand for benzodiazepine receptors may be a derivative of beta carboline-3-carboxylic acid. PMID- 6246537 TI - Beta-Endorphin: dissociation of receptor binding activity from analgesic potency. AB - Biological activities of synthetic camel beta-endorphin and human beta-endorphin (beta h-EP) have been measured by the radioreceptor binding assay, using [Tyr27 3H]-beta h-EP as the primary ligand and by the tail-flick test for analgesic potency. Four synthetic analogs of beta h-EP, namely [Gly31]-beta h-EP-Gly-NH2, [Gly31]-beta h-EP-Gly-Gly-NH2, [Gln8,Gly31]-beta h-EP-Gly-Gly-NH2, and [CH3(CH2)4NH231]-beta h-EP, have also been assayed by the same procedures. Results indicate a clear dissociation of radioreceptor binding activity from analgesic potency. PMID- 6246538 TI - Memory neuron: operating characteristics for the memory component of a neuroconnective brain model. AB - In this paper an attempt is made to deduce the principal operating operating characteristics that a neuron would need in order to qualify as the basic memory component of a sensory memory system. The required characteristics are found to include the possession of many--perhaps more than 100--separately innervated "recording connections," in each of which the constituent synapses can be put in a persisting state of (inhibitory) effectiveness or of ineffectiveness depending on whether the input axon is inactive or is carrying spikes at the time a triggering "recording command" comes to the memory neuron. The synapses of the recording connections must also respond to an "erasing command" by assuming a common prerecording state unaffected by previous history. At other times a synapse-regeneration feature must operate, to counter any decay of effectiveness of connections that have been left by recording in an effective state as well as any acquisition of effectiveness by connections that have been left in an ineffective state. PMID- 6246536 TI - Regulation of hippocampal glutamate receptors: evidence for the involvement of a calcium-activated protease. AB - Specific [3H]glutamate binding to rat hippocampal membranes and the calcium induced increase in this binding are markedly temperature-sensitive and are inhibited by alkylating or reducing agents as well as by various protease inhibitors. N-Ethylmaleimide, chloromethyl ketone derivatives of lysine and phenylalanine, and tosylarginine methyl ester decrease the maximum number of [3H]glutamate binding sites without changing their affinity for glutamate. Preincubation of the membranes with glutamate does not protect the glutamate "receptors" from the suppressive effects of these agents. The proteases trypsin and alpha-chymotrypsin increase the maximum number of [3H]glutamate binding sites. The effects of calcium on glutamate binding are different across brain regions. Cerebellar membranes are almost insensitive whereas hippocampal and striatal membranes exhibit a strong increase in the number of binding sites after exposure to even low concentrations of calcium. These results suggest that an endogenous membrane-associated thiol protease regulates the number of [3H]glutamate-associated thiol protease regulates the number of [3H]glutamate binding sites in hippocampal membranes and that this is the mechanism by which calcium stimulates glutamate binding. The possibility is discussed that the postulated mechanisms participate in synaptic physiology and in particular may be related to the long-term potentiation of transmission found in hippocampus under certain conditions. PMID- 6246540 TI - Histochemical changes in cytochrome oxidase of cortical barrels after vibrissal removal in neonatal and adult mice. AB - The posteromedial barrel subfield of the somatosensory cortex of mice was examined histochemically for cytochrome oxidase activity (cytochrome c oxidase; ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1). In normal mice a high enzymatic activity was found within the barrel hollows, rather than in the sides and septa. Electron microscopic examination indicated that within the hollows reactive mitochondria reside in many dendrites, in some axonal terminals, and in a few neuronal perikarya. After neonatal cauterization of selected row(s) of vibrissae, the corresponding row(s) of barrels appeared as narrowed fused band(s) and their cytochrome oxidase activity was much reduced. Removal of vibrissae in the adult, by either cauterization or repeated plucking, did not cause size changes of cortical barrels. However, there was a significant decrease in the oxidative enzymatic activity within these barrels. Thus, the deprivation of sensory input through damage to, or removal of, the peripheral sensory organ induces an enzymatic response in neurons that are at least two to three synapses away from the periphery. PMID- 6246539 TI - Activation, inactivation, and desensitization of acetylcholine receptor channel complex detected by binding of perhydrohistrionicotoxin. AB - The effects of receptor activation were studied on the interaction of perhydrohistrionicotoxin (H(12)-HTX) with the ionic channel of the nicotinic acetylcholine (AcCho) receptor in membranes from the electric organ of Torpedo ocellata and with the endplate region of the soleus muscle of the rat. In Torpedo membranes, the initial rate (i.e., within 30 sec) of [(3)H]H(12)-HTX bindings to the ionic channel of the AcCho receptor was accelerated 10(2)- to 10(3)-fold in the presence of carbamoylcholine (Carb). H(12)-HTX also inhibited Carb-activated (22)Na(+) influx, over 95% inhibition at 10 muM H(12)-HTX. At this concentration H(12)-HTX did not inhibit [(3)H]AcCho binding to the AcCho-receptor sites. There was good correspondence between the degree of acceleration of [(3)H]H(12)-HTX binding and the stimulation of (22)Na(+) influx over a wide range of Carb concentrations (up to 100 muM). Preincubation of Torpedo membranes with Carb decreased the initial rate of [(3)H]H(12)-HTX binding, as well as the rate of (22)Na(+) influx, which may reflect desensitization of the AcCho-receptor. d Tubocurarine inhibited the agonist-mediated acceleration of [(3)H]H(12)-HTX binding and (22)Na(+) influx. In the soleus muscle endplate, H(12)-HTX inhibited the transient depolarization induced by microiontophoretic application of AcCho; the more receptors activated and channels opened, the stronger was the inhibition by H(12)-HTX. These findings suggest that H(12)-HTX binds to closed and open ionic channels, with a preference for the latter conformation. It is also suggested that the conformational changes associated with activation or desensitization of the receptor can be monitored by studying binding of [(3)H]H(12)-HTX to the ionic channel sites as well as by the AcCho-receptor regulated (22)Na(+) influx. PMID- 6246541 TI - Partial purification and characterization of natriuretic factor from rat kidney. PMID- 6246542 TI - The effects of p-chlorophenylalanine, fenfluramine and alpha-methyltyrosine on marking responses in the male Mongolian gerbil (Meriones unguiculatus). AB - Marking behavior was maintained by testosterone propionate treatment in castrated Mongolian gerbils. p-Chlorophenylalanine (PCPA) enhanced and alpha-methyltyrosine (alpha-MT) inhibited responses. No effect was seen by PCPA in non-TP-treated subjects. Fenfluramine inhibited the response in intact gerbils. The data suggest that serotonergic inhibitory mechanisms exist which are implicated in testosterone dependent marking behavior in the Mongolian gerbil. PMID- 6246543 TI - Effects of dexamethasone, corticosterone, and ACTH on lordosis in ovariectomized and adrenalectomized-ovariectomized rats. AB - The involvement of the pituitary-adrenocortical axis in the control of the lordosis reflex was investigated; In Experiment 1, estrogen-primed ovariectomized (ovx) and adrenalectomized-ovariectomized (adx-ovx) females were treated chronically with dexamethasone, a compound blocking ACTH release from the pituitary. Dexamethasone inhibited lordosis, effectively blocking an adrenalectomy-induced facilitation of the reflex. In Experiment 2, corticosterone was similarly administered chronically; this compound also inhibited lordosis in adx-ovx females. In Experiment 3, acute peripheral administration of synthetic ACTH caused a marked increase in lordosis in ovx females. The results suggest that in the adrenally intact animal, ACTH may exert its effect through adrenal steroids. An acute elevation of adrenal steroids may increase lordosis, whereas a chronic elevation may decrease it. PMID- 6246544 TI - 3H-delta 9-Tetrahydrocannabinol, 3H-cannabinol and 3H-cannabidiol: penetration and regional distribution in rat brain. AB - 3H-delta 9-Tetrahydrocannabinol (3H-delta 9-THC), 3H-cannabidiol (3H-CBD) and 3H cannabinol (3H-CBN) were administered (1 mg/kg) to male rats which were decapitated either 0.5, 1, 15, 30 or 90 min later. The plasma concentration was similar for all cannabinoids throughout the time course. After 5 min greater than 80% of the plasma radioactivity in each treatment was due to metabolites. Radioactivity rapidly entered brain after the administration of 3H-CBD, 3H-CBN, and 3H-delta 9-THC. The concentrations of unchanged 3H-CBD aand 3H-CBN in whole brain were higher than that of 3H-delta 9-THC 5 min after administration. Regional distribution of radioactivity in the brain after 5 min was similar for all three cannabinoids, the only significant difference being in hypothalamus. Coadministration of 3H-delta 9-THC with a five-fold excess of either CBD or delta 9-THC did not produce any significant alteration in the levels of radioactivity in brain or plasma 5 min after their injection. The difference in behavioral activity of delta 9-THC, CBD and CBN cannot be explained by penetrability or regional distribution in the brain. PMID- 6246545 TI - Chronic delta 9-tetrahydrocannabinol administration and schedule-induced aggression. AB - The effects of 0.5 mg/kg and 1.0 mg/kg of delta 9-tetrahydrocannabinol (delta 9 THC) on key-pecking maintained by a response-initiated fixed interval (FI) schedule of food presentation and schedule-induced aggression in the pigeon were studied. Initially, following the administration of delta 9-THC both the rate of key-pecking and attack responding were markedly reduced. Over sessions, tolerance developed to the suppressant effect on key-pecking, with the rate returning to the predrug level. The suppressing effect of delta 9-THC on the rate of attack remained at or near zero throughout the series of delta 9-THC injections. PMID- 6246546 TI - Therapeutic use of natural anthraquinone for other than laxative actions. PMID- 6246547 TI - The physiological basis of laxative action. PMID- 6246548 TI - Effect of rhein on the transport of electrolytes, water, and carbohydrates in the human jejunum and colon. PMID- 6246549 TI - Physiological yardsticks for bowel function and the rehabilitation of the constipated bowel. PMID- 6246550 TI - [A case of complex angiodysplasia of the lower limb. Attempted treatment by embolization]. AB - The authors report a case of complex angiodysplasia of the right lower limb, complicated by an ulcer of the ankle, and associated with a venous dysplasia, arteriovenous fistulae, and malformations in the distal arterial system. A deliberately partial embolization of the arteriovenous communications of the right foot helped to achieve scarring of the trophic disturbance. PMID- 6246552 TI - [Deep vein malformations in the Klippel-Trenaunay syndrome]. AB - Klippel's syndrome is due to a malformation of the deep veins. From 1944 to 1978 we have operated on 614 cases. In 51 % of these cases the malformation concerned the popliteal vein, in 16 % it concerned the superficial femoral vein, and in 25 % both veins were affected. We had only 3 % of iliac malformations and 1 % of inferior vena caval malformation. In the popliteal vein, ageneses and atresias were of equal incidence, but compressions by fibrous bands were much more frequent. In the femoral vein, compressions were most frequent, followed by atresias. Ageneses were very rare. In the iliac vein, atresias were twice as common as ageneses, whereas with the inferior vena cava we only found ageneses. The obstruction to the deep veins can be sectioned but one must also free the supplying vessels. PMID- 6246551 TI - [Klippel-Trenaunay syndrome and phacomatoses]. AB - Several mechanisms can be invoked in order to explain the appearance in a limb of the characteristic triad : naevus, varices and osteodystrophy. Many cases can be explained by the haemodynamic disturbance associated with venous hypertension caused by a venous malformation combined with arteriovenous microcommunications. These are the true Klippel and Trenaunay Syndromes. In a few rare cases the haemodynamic disturbance is caused by one or more arteriovenous fistulae with major flows. These are the Parkes-Weber-Syndromes. Finally, in the more complex syndromes there is the combined triad of naevus, varices and osteodystrophy, together with other genetic disturbances. These are the Phacomatoses. PMID- 6246553 TI - [Klippel-Trenaunay, syndrome or disease]. AB - Two cases which were clinically typical of the Klippel Trenaunay syndrome and in which the integrity of the deep venous system demonstrated by phlebography form the basis for the author's discussion of the various theories and classifications which have been put forward up to now. The authors favour Schobinger's opinion, according to which three varieties of the Klippel Trenaunay syndrome are recognised. Malan's anatomoclinical classification has been adopted : this permits the grouping together of the numerous variations possible in this type of dysplasia. PMID- 6246554 TI - [Some clinical remarks concerning vascular dysplasias]. AB - After a historical review and a review of classification, the author indicates the reasons which lead patients suffering from vascular dysplasias to consult a phlebologist. The clinical symptoms leading to consultation are haemorrhage, leg ulcer, varicose veins, phlebitis, and large legs. Some cases are presented of each of these clinical disturbances. PMID- 6246555 TI - [Klippel-Trenaunay syndrome : cases suggesting embryopathy]. PMID- 6246556 TI - [Micromorphological and clinical aspects of angiodysplasias]. AB - As is known, 1900 Klippel and Trenaunay summarized naevus teleangiectatisuc lateralis, vein ectasias and isolated gigantism to a triad. Seven years later Weber described the same syndrom adding the symptom of arterio-venous fistulas, that he clinically diagnosed. Some authors deduce from this symptomatology two syndroms ; on one hand the Klippel and Trenaunay syndrom and on the other the P. F. Weber-syndrom. As it is shown, in spite of an immense variability of symptoms, arterio-venous short circuits can regularly be demonstrated-clinically, arteriographically or histomorphologically. In addition to this some casuistical examples are presented. Referring to this reports the authors do not agree on separation of Klippel-Trenaunay and Weber syndrom. Considering to therapeutical consequences -- namely surgical -- it should be always cleared up angiographically if hemodynamically relevant arterio-venous fistulas are present. (Due to this fact a divergence to Weber's characterization is given). Relative to the authors opinion the presence of hemodynamically and so therapeutically relevant or obviously hemodynamically non-relevant arterio-venous fistulas does not allowed the separation in two syndroms. Out of this reason the authors nomenclature the described symptomatology as Klippel-Trenaunay-Weber-Syndrom. PMID- 6246557 TI - [Malformations of the lacteals]. AB - For the diagnosis of malformations of the lymphatics is made by the hyperlipidaemia test, which shows a flat total lipids curve without a post prandial peak. Malformation of the lymphatics of the small intestine is responsible for exudative enteropathy, chyloperitoneum, chyluria, lymphoedema with reflux of lymph in the lymphatics of the legs and its complications (chylorrhagia, chylarthrosis), chylothorax, chylopericardium and reflux of lymph in the pulmonary lymphatics. This malformation can also be associated with other disorders : such as the syndrome of Klippel and Trenaunay, and simple lymphoedema of the limbs or genital organs. Lymphography of the intestinal lymphatics carried out during laparotomy after a fatty meal shows the state of the lymphatic vessels, a lack of injection of the cistern of Pecquet, and above all the presence of adventitious vessels allowing the lymph to reach the cervical region. PMID- 6246558 TI - Pituitary adrenocortical response to chronic intermittent stress. PMID- 6246559 TI - Extending the duration of ACTH-induced memory reactivation in an amnesic paradigm. PMID- 6246560 TI - Inactivation of synchronized Chinese Hamster V79 cells with charged-particle track segments. PMID- 6246561 TI - Some observations on the epidemiology of bovine leucosis virus infection in a large dairy herd. AB - Bovine leucosis infection rates were calculated for two years in a naturally infected dairy herd in which serologically positive animals were not preferentially culled. Transmission of infection was found to occur mainly during the winter housing period. No variation in susceptibility to infection with age was found and young animals did not show a prolonged time from infection to sero conversion. PMID- 6246562 TI - The effect of Escherichia coli endotoxins on the concentrations of corticosterone and growth hormone in the plasma of the domestic fowl. AB - The intravenous injection of chickens aged six to 11 weeks with Escherichia coli endotoxins (serogroups O111 and O78) produced a large increase in the plasma corticosterone concentration which was maximal (five to 10-fold) after 1 h and still evident after 8 h. It did not vary with the dose over the range 0.1 to 2 mg/kg and was smaller than that produced by adrenocorticotrophic hormone (ACTH) (20 iu/kg). A decrease in growth hormone concentration was detected between 1 and 2 h after endotoxin administration in six- to seven-week-old birds, this change being opposite to that which occurs in man. PMID- 6246563 TI - The effect of Escherichia coli endotoxins and adrenocortical hormones on plasma enzyme activities in the domestic fowl. AB - The intravenous injection of endotoxins isolated from Escherichia coli serogroups O111 and O78 (2 mg/kg) increased the activities of aspartate transaminase and lactate and sorbitol dehydrogenases in the plasma of six- to 11-week-old chickens during the next 24 h. These changes were compared with those produced by adrenocorticotrophic hormone and beta-methasone and were attributed to tissue damage involving the liver followed by increased enzyme synthesis which may have been induced partly by adrenocortical hormones. Further evidence of liver damage was provided by a fall in the activity of cholinesterase. The alkaline phosphatase activity gave no indication of cholestasis. PMID- 6246564 TI - Experimental infection of calves with two strains of bovine virus diarrhoea virus: virus recovery and clinical reactions. AB - Fifteen calves were inoculated with a mixture of two strains of bovine virus diarrhoea virus (BVDV), the cytopathogenic NADL strain which had been passaged over 20 times n vitro, and the non-cytopathogenic FCS strain, passaged only once after isolation from fetal calf serum. In a second experiment, seven calves received the NADL strain, and eight the FCS strain. The clinical and virological results of the two experiments were compared. In dual infections, the NADL strain interfered with the replication of the FCS strain resulting in less severe disease than the FCS strain alone. The FCS-BVDV was recovered from nasopharyngeal swabs and buffy coat cells whereas the NADL-BVDV was recovered only from nasopharyngeal swabs. The cytopathogenicity of the two strains did not change after passage in vivo. The differences observed are discussed in relation to cultural history and cytopathogenicity. PMID- 6246566 TI - [Diet therapy. Current concepts]. PMID- 6246565 TI - [Coronaviruses in pathology]. AB - The crown-like projections on the surface of the particles permits differentiation of coronaviruses from other riboviruses and their individualization as a distinct family. Recognition of their role in the aetiology of respiratory, enteral and encephalitic infections has promoted investigations for the finding of preventive vaccines. Selection of the strains showed that their immunogenicity depends upon the density and salience of the crown-like projections, the antigenic relationship of the projections determining cross serologic reactions between different species. At present experiments are being carried out on animals with vaccines prepared with antigenically related heterologous cornavirus species, not pathogenic for the host, and with subunitary vaccines prepared from the projections of the homologous species. The Coronaviridae family established on morphologic criteria is thus confirmed by the immunologic relationship and specificity of its members. PMID- 6246567 TI - Effect of lithium carbonate on the functional state and the enzymatic equipment of neutrophils in patients with granulocytopenia. AB - Administration of lithium carbonate, 750 mg daily, during 10 days to 25 patients with essential granulocytopenia, induced an increase of the total leukocyte count, of the absolute count of neutrophils and of the number of neutrophils phagocytizing Staphylococcus aureus Oxford in vitro. An enhancement of acid phosphatase activity in the neutrophils was noted both in the patients and the healthy subjects in the control group. In the patients, the counts of neutrophils exhibiting a positive enzymatic reaction with regard to beta-glucuronidase, myeloperoxidase and alkaline phosphatase were also increased after treatment with lithium carbonate. Based on these results, the authors recommend the clinical application of this treatment in patients with granulocytopenia. PMID- 6246568 TI - Evidence in favor of an anti-invasion factor in cementum or periodontal membrane of human teeth. AB - A casein-agar method for the detection of protease inhibitors has been used on human teeth. Periodontal membranes or cementum have been shown to contain a potent collagenase inhibitor. This inhibitor might explain why the roots of teeth are normally protected against resorption. A similar protease inhibitor has recently been demonstrated in cartilage and there it was called an anti-invasion factor. PMID- 6246569 TI - Study of erythrocytes in a hereditary hemolytic syndrome (HHS): comparison with erythrocytes in lecithin:cholesterol acyltransferase (LCAT) deficiency. AB - Erythrocyte membrane abnormalities in 3 members of a family with a hereditary haemolytic syndrome (HHS) were compared to those previously described in a family with lecithin:cholesterol acyltransferase (LCAT) deficiency. Despite similarities including an increase in membrane phosphatidylcholine, a decrease in phosphatidylethanolamine, stomatocytosis, and a marked decrease in erythrocyte osmotic fragility a number of differences were observed. These included membrane cholesterol content (increased in homozygotes with LCAT deficiency), changes in sodium and potassium content and Na+,k+-ATPase activity (the latter being increased in HHS), changes in acetylcholinesterase and sulfhydryl group latency (present in LCAT deficiency, but not in HHS) and 2,3 DPG content (decreased in HHS, normal in LCAT deficiency. Full compensation of the erythrocyte defect occurred in HHS but the homozygotes for LCAT deficiency were slightly anaemic. It is concluded that, although similar abnormalities in phospholipid composition, osmotic fragility, and erythrocyte morphology exist in these two disorders, the molecular nature of the erythrocyte membrane structural and functional changes in HHS and LCAT deficiency is clearly different. PMID- 6246570 TI - Separation of human bone marrow cells in density gradients of polyvinylpyrrolidone coated silica gel (Percoll). AB - A simple and highly reproducible method is described for separation and density distribution analysis of human bone marrow cells in continuous density gradients of polyvinylpyrrolidone coated silica gel (Percoll). Colony and cluster forming cells in agar separated from the bulk of cells and peaked at densities of 1.063 1.064 g/ml. The enrichment of clonogenic cells was approximately 10 times and recovery varied between 41-321%. The overall recovery of cells was 80% (60-94%). Density distribution analysis of morphologically identifiable cells demonstrated the progressive increase in density with maturation of cells within the granulocytic series: myeloblasts peaked at 1.0624 g/ml, promyelocytes at 1.0734 g/ml, myelocytes at 1.0776 g/ml, metamyelocytes at 1.0799 g/ml and mature neutrophils at 1.0864 g/ml. The eosinophil had the highest density, 1.0904 g/ml, of all cells analyzed. Monocytes and lymphocytes peaked at 1.0661 and 1.0681 g/ml respectively. The light density shift of clonogenic cells of AML and CML reported by other authors was confirmed. PMID- 6246571 TI - Antibody to hepatitis A virus in plasma of Danish blood donors and in immune serum globulin produced in Denmark. AB - Antibody to hepatitis A virus (anti-HAV) was studied in 225 Danish blood donors. The prevalence was found to be 3% in individuals younger than 30 years but then rising with age to 78% in individuals older than 55 years. The titer of anti-HAV in 51 lots of Danish immune serum globulin (ISG) produced from June 1969 to June 1977 was found to vary between 2300 and 5900 except for 2 with titers of 14000 and 28000. The titers did not change during the period and compared well to 3 lots of ISG produced in the USA and selected by the manufacturer because of a high anti-HAV titer. PMID- 6246572 TI - Studies of platelet monoamine oxidase activity in Epstein-Barr and dengue virus infections. AB - As part of a prospective, psychosocial, and biochemical study of infectious mononucleosis, platelet monoamine oxidase (MAO) activity has been evaluated as a host factor. It was found that platelet MAO activity may be a possible predisposing host factor but not a precipitating factor. The results on infectious mononucleosis, a viral disease which involves the host's cell-mediated immune system, are compared with an evaluation of platelet MAO activity in dengue, a viral disorder involving the host's humoral immune system. The platelet MAO activity in these disorders has been compared to that in schizophrenia, a disease for which low platelet MAO activity has been postulated, from retrospective and twin studies, to be a risk factor. One hypothesis suggests that low platelet MAO activity predisposes to development of schizophrenia, but also increases cell-mediated immune system responses. PMID- 6246573 TI - Partial purification and characterization of the high molecular weight latent collagenase from human leukocytes. AB - Two latent collagenases whose apparent molecular weights were ca. 150 000 and 60 000 have been detected in human leukocytes and the partial purification of the high molecular weight component was accomplished by the following steps: acetone precipitation, ammonium sulphate fractionation, gel filtration on Sephacryl S 200, chromatography on DEAE-Sepharose, and a final gel filtration on Sephacryl S 200. After activation by an activator extracted from human rheumatoid synovial fluid, the enzyme was able to cleave collagen into the classical 1/4 and 3/4 fragments, and was inhibited by chelating agents and other typical collagenase inhibitors. PMID- 6246574 TI - [Hypoglycemia: clarification and etiology]. AB - Spontaneous hypoglycemia occurs when the blood sugar falls below 50 mg/dl (2.8 mmol/l) and when neuroglycopenic symptoms appear. For clinical differential diagnosis separation of the hypoglycemias into fasting and postprandial hypoglycemias is suggested. Fasting hypoglycemia may be a symptom of insulinoma. The most important diagnostic tool in detecting insulinoma is still the simultaneous determination of glucose and insulin in plasma during fasting. A raised insulin level during hypoglycemia renders the presence of an insulinoma suspect; during fasting there is an inappropriate fall in blood glucose in relation to the course of the plasma insulin concentration, resulting in an increased insulin-glucose ratio. Recently determination of the fasting proinsulin level has been recommended as raised concentrations are pathognomonic for the presence of insulinoma. Evaluation of postprandial hypoglycemia is performed by oral glucose tolerance test with late glucose concentration determinations after three and four hours. This makes it possible to differentiate between reactive hypoglycemia in mild diabetes mellitus and "functional" reactive hypoglycemia, the most frequent cause of hypoglycemia. PMID- 6246575 TI - Transposable genetic elements. PMID- 6246576 TI - Biomaterials. PMID- 6246577 TI - Insertion of a new gene of viral origin into bone marrow cells of mice. AB - DNA containing the herpes simplex virus thymidine kinase (HSVtk) gene was used to transform wild-type tk+ mouse L cells to a tk++ status in vitro using methotrexate as a selective agent. HSVtk DNA was also used to transform mouse bone marrow cells in vitro. Transformed marrow cells injected into irradiated and methotrexate-treated recipient mice gave rise to proliferating cells which in some cases dominated the marrow population and which contained HSVtk gene sequences. PMID- 6246579 TI - Simian virus 40 crystals. AB - Small (10 to 150 micrometers) cubic crystals of simian virus 40 have been grown by ammonium sulfate precipitation. Electron micrographs of thin sections from these crystals reveal ordered arrays of virus particles. PMID- 6246578 TI - Pro-adrenocorticotropin/endorphin-derived peptides: coordinate action on adrenal steroidogenesis. AB - A synthetic peptide, representing a portion of the 16K (16,000 dalton)-fragment sequence within the pro-adrenocorticotropin/endorphin precursor molecule, potentiates the steroidogenic action of the 1 to 24 portion of adrenocorticotropin [ACTH(1-24)] on the rat adrenal cortex. The peptide has 27 amino acid residues and consists of gamma-melanotropin with a carboxyl terminal extension. It affects both the inner and outer adrenocortical zones of hypophysectomized animals, as evidenced by a synergistic augmentation of corticosterone and aldosterone production, respectively. The peptide can be distinguished from adrenocorticotropin by its activation of cholesterol ester hydrolase and its failure to stimulate cholesterol side-chain cleavage. PMID- 6246580 TI - Coronary artery spasms and heart disease. PMID- 6246581 TI - Oxygen consumption and cellular ion transport: evidence for adenosine triphosphate to O2 ratio near 6 in intact cell. AB - Oxygen (O2) consumption and net K+ uptake were measured simultaneously upon reintroduction of K+ into a K+-depleted suspension of renal tubules. The K+/O2 stoichiometries of 11.8 +/- 0.2 and 8.4 +/- 0.6 were obtained for reduced nicotinamide adenine dinucleotide- and flavoprotein-linked substrates, respectively. These values complement classical K+ to adenosine triphosphate (ATP) and ATP/O2 stoichiometries, thereby demonstrating a remarkably efficient coupling between the processes of Na+- and K+-dependent adenosinetriphosphatase mediated ion transport and oxidative phosphorylation within the intact cell. PMID- 6246582 TI - Cholecystokinin receptors in the brain: characterization and distribution. AB - Specific cholecystokinin binding sites in particulate fractions of rat brain were measured with iodine 125-labeled Bolton-Hunter cholecystokinin, a cholecystokinin analog that has full biological activity. Binding was detected in brain regions known to contain immunoreactive cholecystokinin. Binding was saturable, reversible, of high affinity (dissociation constant, 1.7 x 10(-9) M), and was inhibited by cholecystokinin analogs but not by unrelated hormones. PMID- 6246583 TI - Opiate receptor function may be modulated through an oxidation-reduction mechanism. AB - Cupric ion, a thiol oxidant, caused naloxone-reversible analgesia when injected intracerebroventricularly in mice; its potency was close to that of morphine. Dithiothreitol, a thiol reductant, reversed the analgesia induced by cupric ion and antagonized analgesia induced by morphine. Oxidized dithiothreitol had no effect. These findings, together with evidence for redox modification of opiate receptor binding in vitro, suggest that a mechanism of oxidation-reduction of thiols may modulate opiate receptor function. PMID- 6246584 TI - Mitochondrial water in myocardial ischemia: investigation with nuclear magnetic resonance. AB - Nuclear magnetic resonance studies of mitochondria isolated from ischemic hearts after coronary vessel occlusion indicated a decrease in water proton relaxation times. This change coincided with a decrease in the hydration of the samples. It is suggested that in ischemia, changes in macromolecular hydration may be one of the first mechanisms to alter function in the mitochondria, which are vital to the energy-transducing process in heart muscle. PMID- 6246585 TI - Beta-adrenergic-receptor localization by light microscopic autoradiography. AB - beta-Receptors were identified in rat brain by a light microscopic autoradiographic technique. The procedure involved binding 3H-labeled dihydroalprenolol to beta-receptors in intact slide-mounted tissue sections and generating autoradiograms by the apposition of emulsion-coated cover slips, Biochemical analysis of the binding indicated that these conditions provided a high degree of selective labeling of beta-receptors. High densities of receptors were found in superficial layers of the cerebral cortex, throughout the caudate putamen, in the periventricular nucleus of the thalamus, in the molecular layer of the cerebellum, and in other areas. These results are in agreement with other electrophysiological and histochemical data. This radiohistochemical approach should be an important addition to other methods for mapping functional catecholamine neuronal pathways and sites of hormonal action. PMID- 6246586 TI - Levels of batrachotoxin and lack of sensitivity to its action in poison-dart frogs (Phyllobates). AB - Batrachotoxin is present in remarkably high amounts in the skin of Phyllobates terribilis. Levels of batrachotoxin tend to be reduced when P. terribilis is maintained in captivity, but even after being confined for up to 6 years, these frogs were still at least five times more toxic than other Phyllobates species used by natives for poisoning blowgun darts. Batrachotoxin was not detectable in F1 progeny reared to maturity in captivity. Nerve and muscle preparations from wild-caught frogs and from the nontoxic F1 frogs were both insensitive to batrachotoxin. The regulatory site controlling sodium-channel activation and permeability appears to have been minimally altered to prevent interaction with batrachotoxin, but is still sensitive to other sodium conductance activators (veratridine, grayanotoxin) to which the frogs arenot exposed naturally. PMID- 6246587 TI - [Neurosurgical observations of central nervous system parasitic diseases]. AB - Two main diseases are met, though seldom, in France (mostly in African patients): 1) hydatic cyst, the outcome of which is good after ablation; 2) multiple cysticercosis, often fatal. Furthermore two very rare cases are reported, one is a cerebral cryptococcosis, the other is an extra-dural spinal filariosis. PMID- 6246588 TI - [Headache related to sexual intercourse (author's transl)]. AB - Coital cephalalgic (CC) is rare (1/360 headaches); it occurs more frequently among men. Out of 16 unpublished cases, in 4 cases, CC was the inaugural symptom of vascular attack. In the 12 other cases, CC was isolated or primary. According to the time of onset of headache during coit one may distinguish three types: 1) early CC usually moderate and short lasting; 2) orgasmic CC, abrupt, severe, lasting 15 to 20 minutes; 3) late CC of long duration (hours, days) follows sometimes orgasmic CC. Isolated CC is usually repetitive but capricious, episodical, not periodical. Prognosis is good. Mechanism is mainly vascular and muscular. The role of high blood pressure, migraine, and psychological factors is discussed. PMID- 6246589 TI - [Clinical and biological patterns of hyperthyroidism in elderly patients (author's transl)]. AB - Aetiological, clinical and biological patterns of hyperthyroidism are studied in 22 consecutive patients over the age of 65 years. In this group the frequency of toxic multinodular goiter and Graves disease are grossly the same. A previous iodine administration could be a significant aetiologic factor in 8/22 patients. The clinical symptomatology is characterized by the predominance of cardiovascular disorders and by the mildness or absence of the other symptoms of thyrotoxicosis. The classical abnormalities of thyroid function tests are only found in 65% of our patients. The others have high total and free thyroxine (T4) and normal triiodothyronine (T3) plasma levels with a marked increase in reverse T3 (RT3) levels. These abnormalities result possibly from an impairment of the peripheral conversion of T4 to T3 as it is seen in fasting or in sick euthyroid patients. Most of our hyperthyroid patients had an associated disease and were undernourished. In the elderly patient the determination of plasma T4 by a radioimmunoassay and the T3 uptake test are the best screening methods for detecting an often hidden thyrotoxicosis. PMID- 6246590 TI - [Short term prognosis of ulcerative colitis (author's transl)]. AB - The authors analyse the short-term prognosis of ulcerative colitis from a series of 65 patients followed during ten years and treated with the same attitude. The results are compared to those of the most important published, from which they differ just a little. The medical treatment is effective in 84,6% of cases. The mortality of first attack is 6,1%. Only 1,4% of patients in our series are colectomised. It seems that the short-term prognosis has been slightly better during the last few years perhaps because of improvement in management and appearance of corticosteroids and/or salazosulfapyridine. The factors of bad prognosis in a first attack are its severity, its extension to the whole colon, its beginning after 60 years. PMID- 6246591 TI - [Treatment of bronchial carcinoid tumors. 29 cases (author's transl)]. AB - The authors study the modalities of the surgical treatment of bronchial carcinoid tumors with regard to personal series of 129 cases and to 595 observations of the literature. PMID- 6246592 TI - [Acute renal failure induced by retroperitoneal fibrosis revealing Hodgkin's disease. A case report. Five years complete remission with surgical and medical treatment. Subsequent fatal bronchogenic carcinoma (author's transl)]. AB - A 57 year-old-man with acute renal failure was diagnosed as having retroperitoneal fibrosis. Malignant lymphoma is suspected because of peripheral lymphadenopathy, but biopsies are unrevealant. Nephrostomy restores kidney function. Many other histologic samplings performed during three laparotomies are necessary to diagnose Hodgkin's disease. Nephrostomy is complicated with iterative acute pyelonephritis and septicaemias which make chemotherapy unadvisable. Ureterolysis is unsuccessful. Urinary tract infection disappears after uretero-ileoplasty. Subsequently chemotherapy induces a complete remission during 5 years with normal renal function. We review two previously reported cases of this unusual cause of malignant retroperitoneal fibrosis. Diagnostic procedures and therapeutic management are discussed. PMID- 6246593 TI - [Surgical complications of the diverticular disease of the colon. Series of 110 cases (author's transl)]. AB - The authors are reviewing a series of 110 cases of operated diverticulitis. Emergency operations mainly concerned cases of fecal peritonitis. Mortality is still fairly high (27 percent). In these cases, immediate resection (two-stages operation) brings better results than the classical three-stages operation. The latter, however, remains in some cases a safe solution. Concerning chronic patients, surgical procedures always require immediate resection, whatever the anatomic lesions can be. Hartmann operation has been given up by the authors. Presently, in every cases, continuity is carried out by ideal colectomy or by anastomosis protected by a transverse colostomy. In such cases, mortality has been, 2,6 percent and functional results are most satisfactory. PMID- 6246594 TI - [Acute mercury poisoning in children. Report on four cases (author's transl)]. AB - The authors report four cases of acute mercury poisoning in children ranged from one week to twelve years of age. All were of favourable course and one of them is particularly well-documented with regard to mercury excretion. Case reports are followed by a clinical study of mercury intoxication with a review of literature about recent therapeutic advances. PMID- 6246595 TI - [Cytology in single "cold" thyroid nodules (author's transl)]. AB - The authors report their own experience about 242 histocytologic correlations of single "cold" scintiscan thyroid nodules. That is to say 70,5% in malignancies and 91,8% in benign lesions. PMID- 6246596 TI - [Bilateral nephrectomy by embolization of the renal arteries: a report on five cases (author's transl)]. AB - Selective bilateral renal artery embolization was performed in 5 patients because of severe hypertension not responding to conventional medical treatment, in two patients on repeated dialysis; severe nephrotic syndromes with chronic renal insufficiency in the three other patients. A significant drop in blood pressure occurred in only two of the hypertensive patients, about 40 days after embolization. Bilateral surgical nephrectomy was required in the other patient because of persistence of residual vascularization and high RAP. Excellent results were obtained in the 3 patients with a nephrotic syndrome, with disappearance of proteinuria and anuria following the embolization. For this method to be effective, the arterial obliteration has to be complete and definitive. When symptoms persist or there is a relapse, especially in the cases with hypertension, a repeated arteriographic examination and complementary embolization has to be envisaged. Further experience with this method is necessary in order to compare the results with those obtained after bilateral surgical nephrectomy. Medical treatment with agents toxic to the tubules, in cases of the nephrotic syndrome, has apparently not produced the results expected. The relative simplicity of this embolization procedure has to be underlined, together with the fact that it is free from major complications when performed by surgeons trained in its use, on the condition that purification be carried out immediately following embolization. PMID- 6246598 TI - [Aneurysms of the pancreaticoduodenal arteries associated with thrombosis of the coeliac artery (author's transl)]. AB - Aneurysms of the pancreaticoduodenal arteries are rare, but are becoming discovered relatively more frequently because of the development of modern angiography, as has been suggested by recent publications on this subject. Our work is of interest because the diagnosis was made before operation, and a complexe angiographic study permitted the most appropriate surgical treatment possible. PMID- 6246597 TI - [Plasma cells leukaemia, cryoglobulins and antithrombin (author's transl)]. AB - Although primitive plasma cells leukaemia is uncommon, it still stands in a particular place among malignant lymphoplasmocytary syndroms. It borrows from multiple myeloma and acute leukaemia some of its clinical and biological manifestations. Its course is quickly adverse, its treatment ineffective and the average life expectation is three months. PMID- 6246599 TI - [Severe cerebellar symdrome during aprindine treatment (author's transl)]. AB - The authors, report a case of severe cerebellar syndrome, (preventory to remain standing) and connect with the dose of aprindine. This complication is coming with a little dose, facilitated with a minor renal insufficiency and a pre existent neurologic disorder. PMID- 6246600 TI - [Multiple hydatidosis: hepatic, splenic, peritoneal and gynaecologic locations (author's transl)]. AB - We report the case of a young Algerian female with a voluminous abdominal tumour suggestive of a hydatic cyst of the liver. Complementary examinations (radiography of adjacent organs, ultrasonography, coelio-mesenteric arteriography, hepatic scanning) revealed two additional abdominal cysts. Furthermore, gynaecologic examination and ultrasonography revealed one intra uterine hydatic cyst. At laparotomy however, the surgeon removed sixteen abdominal and five pelvic cysts, all of them containing brood capsules. It should be noted that one eleven centimeters-diameter splenic cyst was discovered only at operation. The authors point out the rarity of the uterine location of hydatidosis and stress the difficulty of the preoperative localization of all the cysts. In these widespread forms of the disease, complementary flubendazole treatment could be useful. PMID- 6246601 TI - [An exceptional but very serious complication of blepharoplasty. Case report]. AB - The observation concerns a case of amaurosis which set in several hours after blepharoplasty and which was not reported by the patient before it had been discovered by examination. The haematoma was average, the eyeball showed no exophthalmos, but normal consistency and a normal fundus. Treatment was exclusively medical, but unsuccessful. The authors have studied the literature in order to obtain an idea of frequency, suggested etiologies and the treatments proposed. The preoperative arterial spasm requires medical treatment; the retro bulbar haematoma raises the question of surgical treatment for drainage in minor cases and paracentesis in more serious cases. PMID- 6246602 TI - [Angio-immunoblastic lymphadenopathy (author's transl)]. AB - A review of the literature about angio-immunoblastic lymphadenopathy since 1972 Flandrin's first description, attempts to define the main clinical, biological characteristics and clinical course of this disease. Clinically adenopathy, fever, weight loss, often hepatosplenomegaly of the appear as being constant. Hemolytic anemia and polyclonal hyperglobulinemia are the most common biological signs of this immunological disorder. In despite of spontaneous remissions, prognosis is severe. Infections complications are common and often fatal. Transformation in immunoblastic sarcoma is possible. PMID- 6246603 TI - [Hypophysphatemia (author's transl)]. AB - Too often neglected, dosage of phosphatemia should yet be kept on mind. The role of phosphorus in bone mineralization and regulation of acid-base balance is well known. Phosphorus is also an energy purveyor during numerous biologic reactions, and deep deprivation may lead to a lot of pathologic situations, sometimes severe. Mild hypophosphatemia is not rare and occurs in various clinical or therapeutic circumstances; deep hypophosphatemia is rather uncommon, occuring chiefly during hyperalimentation or realimentation of starving patients, especially alcoholics. Deep hypophosphatemia (by depletion or transfer) mainly induces clinical and pathological manifestations; they are subsequent to alterations of glucose metabolism, leading to a failure in ATP and 2,3 DPG synthesis. These metabolic events particularly explain muscular and hematological manifestations of hypophosphatemia. Phosphorus loading per os, or in severe cases intravenously corrects the biological abnormalities and improves clinical manifestations. PMID- 6246604 TI - [Human basophil degranulation in pollinosis: correlation with skin-test diameter (author's transl)]. AB - A human basophil degranulation (HBD) performed on an enriched basophil suspension (by gradient density) was applied in 95 subjects with 3 dilutions of grass pollen extract. Concordance with intradermal skin-test (ST) results reached 90% for wheal and 94% for flare. In 45 positive ST subjects, mean (+/- s.e.m.) of degranulation index was 54,1 +/- 4,2, 54,9 +/- 4,7 and 35,7 +/- 4,9 respectively for dilutions of 10(-4), 10(-6) and 10(-8) of grass pollen. Mean was 6,1 +/- 1,6, 8,2 +/- 1,7 and 8,5 +/- 1,6 in 50 negative ST subjects. In positive ST patients, a significant correlation (r = 0,53 p less than 0,001) appeared between ST diameter (flare) and degranulation index. HBD appears as reliable as RAST or automated histamine analysis but more easy to perform. It permits pharmacological studies of drugs inhibiting human basophil degranulation. PMID- 6246605 TI - [What should be known of the Vogt-Koyanagi-Harada disease? (author's transl)]. AB - The Vogt-Koyanagi-Harada disease is an unusual affection, characterized by a meningeal syndrome, an ocular syndrome involving the anterior or posterior segment of the eye, and at last, manifestations of skin involvement such as poliosis, vitiligo and alopecia. Nowadays, the physiopathologic hypothesis, the most admitted, is the one of auto-immune process regarding the uveal pigment. Nosologically speaking, clinical epidemiologic and etiopathogenic arguments have allowed to join the Harada and Vogt-Koyanagi diseases under the same name: the Vogt-Koyanagi-Harada disease. The same arguments, except the epidemiologic ones, allow to make a similarity between this affection and uveo-meningitis on the hand, sympathetic ophthalmitis on the other hand. The use of oral corticosteroids and eventually immuno-suppressive agents constitute the only therapeutic methods, nowadays. PMID- 6246607 TI - [Preventive treatment of thrombo-embolism in general surgery. A report of 5 242 observations (author's transl)]. AB - 5 242 patients in a ward of general surgery have been submitted to prevention by subcutaneous injection of calcium heparinate. In all coagulolytic balance has been measured by thromboelastogram on whole blood. The aim was to reduce any hypercoagulability and maintain orthocoagulability. Three fourths of the patients had preoperative hypercoagulability, which may be responsible of precocious migrations. Except emergency, this hypercoagulability was first treated. The heparin dosis was scheduled according to age, weight and degree of hypercoagulability, and the treatment maintained at least 15 days. These are the results: thromboembolism 2,48 % (lethal 0,76 %). All registered accidents were the consequence of gross error. Heparinotherapy has been stopped in only 3 patients; there was no special hemorrhage during operation. PMID- 6246606 TI - [Hepatic manifestations in typhoid fever (author's transl)]. AB - Typhoid fever is always endemic in Ivory Coast. Among the various visceral injuries able to arrive during the course of the illness, a study of hepatic manifestations realized in 279 patients show, by the realization of systematic LBP, that, beside clinically and/or biologically certain forms, an hepatic injury is histologically constant. Aetiological, clinical, biological, diagnostic and therapeutic particularities connected with the hepatic localizations are considered and compared with findings of other authors. To remark, in Ivory Coast, on one hand the great predominance of Eberth bacillus aetiology, on the other hand the lack of statistically significative relation with drepanocytary waste. The pathogenic signification of the constancy of the hepatic injury and its peculiar histological pattern of non specific reactive hepatitis is discussed. PMID- 6246608 TI - [The risk factors of bladder tumors stage "A". Description of a new parameter (author's transl)]. AB - 199 cases of carcinoma of the bladder stage A were reviewed with a follow-up from 5 to 15 years. Some "factors of risk" can be deducted from this study. The first is the depth of the invasion of the submucosa when it can be specified. If the superficial part only is invaded (these tumors are called A1) the understaging is less important and the survival rate is much better than when the chorion is totally invaded (called A2). The grade of the tumor is also significant, grade III having a more favorable prognosis than grade IV. The topography of the tumor influences the prognosis: the worse are the tumors of the bladder neck or of this trigone. The other factors of risk are: the rapidity of recurrences, the volume and the number of the tumors: when they are big and multiple, the prognosis is particularly bad, the type of differenciation: the cylindric tumors are worse than the urothelial or epidermoid. PMID- 6246610 TI - [Must we teach, today, the MCHC (Mean Corpuscular Haemoglobin Concentration)? (author's transl)]. AB - Automatic cell counters introduce a new interpretation of the MCHC. The automatic MCHC does not fall in cases of thalassemia or of iron deficiency, except in the severest; so it serves now little practical purpose. The manual MCHC continues to be a useful index of hypochromia, but does not reflect the true haemoglobin concentration in red cells, and it remains less and less in use. PMID- 6246609 TI - [Toxoplasmic pneumonia with generalization (author's transl)]. AB - An anatomo-clinical observation of toxoplasmic pneumonia with generalization in a six-year old child is reported. The serology of toxoplasmosis is positive. The histopathological examination revealed an interstitial pneumonia with toxoplasma located in the tumified alveolar lining cells and in the intra-alveolar macrophages. Parasitic lesions were also observed in the myocardium, peripheral striated muscle, liver, spleen, adrenal gland, lymph nodes, digestive tract and bone marrow. In the absence of the isolation of a toxoplasma strain, the diagnosis was based on the examination of a bone marrow smear performed the day before death. The proliferating forms of Toxoplasma gondii were abundant and characteristic. These data were confirmed by an ultrastructural study of toxoplasma in the lung and myocardium of the patient. In rapidly evolutive generalized toxoplasmosis of this type, the existence of a particular site is obvious but difficult to define. However, this study points out the usefulness of a bone marrow study in the hope of determining an etiological diagnosis with little delay which would thus increase the chances of an effective therapy. PMID- 6246612 TI - [Diagnostic value of breast cytology (author's transl)]. AB - The comparison between clinical examination, mammography, thermography and fine needle aspiration cytology shows the usefulness of cytology in differential diagnosis of benign and malignant breast tumours. The cytology shows the real nature of benign suspicious and malignant mammographic and thermographic results. Specially in the younger patients cytology identifies early tissue changes, invisible on mammography. Application of the TNM classification shows TOT1 T2 tumours 72% of the material, with 90% positive cytologic results. PMID- 6246611 TI - [Acute pseudo-occlusion of the colon (author's transl)]. AB - The authors describe 9 cases of acute dilatation of the colon in which no obstruction was detected. This syndrome, described by Ogilvie is relatively rare but needs to be recognized by the radiologist because of the therapeutic consequences involved. Radiological examination is, in fact, essential in order to exclude any mechanical obstruction. Furthermore, the degree of caecal distention is the deciding factor for surgical intervention, to avoid perforation and peritonitis. Pseudo-occlusions of the colon may occur after very different pathological conditions, and though their physiopathology is still obscure, they are certainly related to disorders of the autonomic nervous system supply to the colon. PMID- 6246613 TI - [Carcinoembryonic antigen in carcinoma of the uterine cervix. Correlations with clinical stage, histopathology, and survival about 115 cases (author's transl)]. AB - Carcinoembryonic antigen is elevated in the serum of approximately 35% (35/98) of patients with carcinoma of the uterine cervix. The incidence of elevated serum CEA is not related to stage of disease, histopathology, lymphangiogram and survival rate. Carcinoembryonic antigen levels return to normal after curative radiation therapy (25/32). Persistently high values after irradiation are indicative of residual disease (3/32). Reappearance of CEA, with a progressive rise evoke a recurrence, and may precede the clinical diagnosis. PMID- 6246614 TI - [Cytology in the diagnosis of prostatic cancer (author's transl)]. AB - We are reporting our 20 years experience in the cytological diagnostic study of prostatic cancer. We studied at the same time, urinary cytology and prostatic histology in 217 patients. There were 50% false positive results with urinary cytology. Franzen aspiration enabled us to diagnose 81% of all prostatic cancers. These two methods are possible on an out-patient basis and enable us to determine high risk patients and to diagnose prostatic cancer earlier. PMID- 6246615 TI - [An unusual cause of intestinal infarction: cholesterol embolization (author's transl)]. AB - The authors report the observation of an infarction of the small bowel caused by cholesterol embolization. A review of the literature shows the rarity of such cases. Nevertheless, this etiology should be considered in gastrointestinal bleeding in atheromatous people. PMID- 6246616 TI - [Right atrial myxoma - about a case revealed by a pseudopericarditic symptomatology (author's transl)]. AB - The authors relate a case of right atrial myxoma, developing as an inflamatory pericarditis. They insist on the misleading aspect of these tumors, on the delay usually occuring before the diagnosis can be reached and on the notable contribution of echocardiography which should be considered as the main investigation in future and should doubtless be sufficient for the cardiac surgeon, while permitting to avoid furthermore invasive investigations (catheterization and angiography). PMID- 6246617 TI - [Laryngeal edema and alveolar hypoventilation as primary manifestations of hypothyroidism (author's transl)]. AB - Laryngeal manifestations are well known and relatively frequent in hypothyroidism. For example horseness, which is due to edematous infiltration of the larynx and vocal cords is often the patient's chief complaint, prompting his initial consultation with a specialist. Of much rarer occurence, however is the concomitant development of laryngeal edema and acute respiratory failure. We report one such case history below. PMID- 6246618 TI - [Autonomous thyroid nodule spontaneously cured by cystic degeneration on a thirteen aged girl (author's transl)]. AB - On a thirteen-aged girl an autonomous thyroid nodule with hypersecretion, has run its course towards hemorragic necrosis with suppression of hypersecretion. If partial cystic degeneration of autonomous thyroid nodule is frequent, it rarely occurs when extra-nodular thyroid tissue is completely suppressed, with clinical "cure". PMID- 6246619 TI - [Neurotoxoplasmosis. Description of a case of an acquired meningo-encephalitis (author's transl)]. AB - The authors report a case of meningo-encephalitis in a 28 year-old man, who was hospitalized in emergency after a generalized epileptic crisis, which occured after a period of fever and neuro-psychiatric troubles. This was followed rapidly by a comatose stage (third grade). All investigations to find an etiology were unsuccessful except: positive toxoplasmosis serology at 720 IU/ml with IgM fluorescent antibodies, then at 2 600 IU/ml. The level of fluorescent antibodies in the CSF was 1/16. Clinical evolution was favorable with resolution of the comatose stage, and disappearance of the meningitis. PMID- 6246621 TI - [Treatment of alcoholism in hospitalized patients (author's transl)]. AB - Patients admitted to a regional psychiatric hospital for alcoholism were treated with tiapride. A total of 131 patients were treated with this therapy among 191 admissions, 47,89p. cent of them being in a confusional oneiric state. Results were compared to those obtained by previous therapy. The administration of tiapride reduced the number of confusional oneiric states provoked by withdrawal after admission by 20 p. cent, and produced a 44 p. cent reduction in the duration of those present at the time of hospitalization. Confused patients became significantly more alert and autonomous, thus reducing the work-load of the nursing staff and greatly assisting the routine running of the department. PMID- 6246620 TI - [Effects of metoprolol, practolol, and propranolol after isoprenaline injections in asthmatic patients (author's transl)]. AB - The effects of two beta-blockers, one non-selective, propranolol, the other beta 1 selective, metoprolol, were studied in 8 asthmatic patients. Practolol and a placebo were used as reference products. Heart rate, blood pressure, MEV, and muscle tremor were measured at rest and after isoprenaline infusions at different concentrations. In patients receiving placebo, isoprenaline caused an increase in heart rate, MEV, systolic BP, and muscle tremor, and a reduction in diastolic BP. After propranolol, the effects of isoprenaline on heart rate, MEV, and muscle tremor were almost completely blocked, and modifications in systolic and diastolic BP were only slightly affected. Metoprolol and practolol did not inhibit the increase in MEV induced by isoprenaline, but they reduced the increase noted in the heart rate. These results demonstrate the beta 1 selectivity of these two beta-blockers. Contrary to propranolol, metoprolol and practolol did not block the increased muscle tremor provoked by isoprenaline: muscle tremor must be dependent on beta 2-receptor activity. As the effect of isoprenaline on the MEV was not inhibited by beta 1-selective beta-blockers, these can be prescribed for asthmatic patients in association with beta 2 stimulants. PMID- 6246622 TI - [Prevention of colorectal cancers (authors transl)]. AB - Colorectal cancers are now at first rank of visceral cancers, before lung cancer. An early detection and a modification of our dietary habits can prevent such cancers. PMID- 6246623 TI - [Very long survivals of chronic granulocytic leukemia (author's transl)]. AB - Following busulfan induced bone marrow insufficiency, a patient witha chronic granulocytic leukemia (CGL) has had a survival lasting 18.5 years. During remission, chromosome studies on bone marrow have not shown Philadelphia chromosome (Ph 1). There was no correlation between this observation and initial pronostic factors from literature. Analysis of 14 cases (13 from literature) of prolonged survival showed that Ph 1 was absent in 4 cases when only 15% of CGL are initially Ph 1 negative. Therapeuticcaryoconversions were probable. Recently attempts have been made to eradicate the abnormal Ph 1 positive clone. Some hopeful results are reported. PMID- 6246624 TI - [Complications after perhexiline maleate and amiodarone chlorhydrate treatment in a same patient: hypoglycemia, polyneuritis and hyperthyroidism (author's transl)]. AB - The authors report the case of a 65 year old man treated with amiodarone chlorhydrate since 4 years and perhexiline maleate since 15 months, admitted for constitutional symptoms with fever, neurologic troubles particularly polyneuritis and pronounced hypoglycemia. A diagnostic of hyperthyroidism was made and attributed to amiodarone. The hypoglycemia and the polyneuritis were related to perhexiline maleate as other signs presented by the patient. All the symptoms disappeared after discontinuation of the drugs. The complications secondary to maleate perhexiline administration are reviewed. PMID- 6246625 TI - [Extra skeletal Ewing's sarcoma. Report of two cases. Ultrastructural study of one case (author's transl)]. AB - The authors report two cases of extra skeletal Ewing's sarcoma. The first case concerns a 26 years old woman presenting a tumor at the level of the sacrum area, locally recurrent, metastazing to the lungs and the lumbar column, despite of radiotherapy and chemotherapy and leading to death after a course of 18 months. The second one is that of a 30 years old man bearing a tumor of the shoulder area probably already metastazed to bones, rapidly recurrent and metastazing to the lungs and cause of death after 9 months in spite of intensive therapy. About these 2 observations a review of the literature of the cases of extra skeletal Ewing's sarcoma is done. Whatever nosologic discussion it seems that Ewing's sarcoma may present essentially as a tumor of soft tissues. An ultrastructural study has been performed in the second case. The findings are similar to those reported in Ewing's sarcoma. PMID- 6246626 TI - [Meningeal leukemia during acute promyelocytic leukemia (author's transl)]. AB - The authors report the case of a meningeal leukemia occuring during the remission stage of an acute promyelocytic leukemia. The data from literature about the meningeal leukemia of acute granulocytic leukemias, the expected long survival of acute promyelocytic leukemias lead to think that this meningeal complication must be systematically prevented. PMID- 6246627 TI - [Isoenzyme BB of creatine phosphokinase: its place in pulmonary pathology (author's transl)]. AB - From the sera or pleural effusions of 29 patients among 58 suffering of bronchopulmonary cancer we found a CK BB isoenzyme (CK EC 2.7.3.2). There is no false positive in sera of our group control. Lung homogenates and alveolar macrophages are found to be rich with this fraction. Is this isoenzyme a cancer marker for the broncho-pulmonary tract? PMID- 6246628 TI - [Myotonic dystrophy severity (Steinert's disease) (author's transl)]. AB - Four family cases of Steinert, myodystrophy are reported. The severity of the early onset form is specially noted. This form presents pulmonary complications and mental deficit. The influence of the myodystrophy on the pregnancy is discussed and an explanation of the disturbance of the oesophaguspharynx motility is presented. Physiopathogenesis problems of the Steinert's disease are noted. PMID- 6246629 TI - [Thrombopenia and radial aplasia: 2 cases with platelet function and ultrastructural studies of megakaryocytes and platelets (author's transl)]. AB - The authors report on two cases of congenital thrombopenia with radial aplasia. Both children display several birth defects and a mild thrombopenia; hemorragic manifestations occured in the first case only. Megakaryoblastic to platelets series, as studied with electronic microscopy, show small-sized, "microcytic" and hypogranular megakaryocytes, displaying a maturative disorder (dysmegakaryocytopoiesis). In functional studies, platelets of the first patient show an imperfect nucleotidic release and do not agregate normally with ristocetin. The second case exhibits mostly a PF3 reduction. The variety of expression of the megakaryocytic-platelets disorders appears likewise in the skeletal and visceral malformations. The whole disorder could be ascribed to a pleiotropic abnormal gene with a variable expressivity. PMID- 6246630 TI - [Recent advances in isotopic exploration of the skeletal system in prostate cancer (author's transl)]. AB - Skeletal isotopic exploration is fundamental in patients with prostatic cancer. Bone scintiscan is reliable. Its sensibility can be increased by using new radioactive isotopes and quantitative isotopic explorations. Bone marrow histologic study is indicated in case of a doubtful diagnosis, when there is a discordance between radiological and isotopic exploration. PMID- 6246631 TI - [Tiapride use in neoplasic algia (author's transl)]. AB - The tiapride, usually prescribed in neurologic pathology, has been used in ENT carcinoma pain. On 30 cases of this study, we got 18 good results, that means a decrease of the pain in 60% cases. In all the cases, the tiapride was well tolerated. PMID- 6246632 TI - [Sensibility to insulin in obese children (author's transl)]. AB - The glucose and immuno-reactive insulin blood levels of 46 obese children and nineteen controls were measured during the intra-venous glucose tolerance test. The glucose tolerance of the obese children was normal, whereas their blood insulin curves demonstrated hyperinsulinmeia. The sensibility to exogenous insulin in 29 of these children was within normal limits during the hypoglycemic tolerance test induced by injection of intravenous insulin. The factors explaining endogenous insulin resistance have not yet been elucidated. PMID- 6246633 TI - [Diagnostic value of aspiration biopsy of thyroid cysts (author's transl)]. AB - In the country of Krakow, which is an endemic place for thyroid diseases, most of the thyroid cysts are related to inflammatory reactions and, therefore, they may be treated, but there are also some malignant tumors which must not be overlooked. The aspiration biopsy of 124 cysts of the thyroid enables the authors to compare the results of the cytological examination to the biochemical assays of the fluid and to identify rapidly evolutive inflammatory cysts, slowly evolutive resorptive cysts and cancerous cysts. PMID- 6246634 TI - [Occlusions of the middle cerebral artery and its branches: Correlations between clinical and angiographic findings (author's transl)]. AB - The authors studied 60 patients with occlusions of the middle cerebral artery, of which 30 were partial occlusions and 30 complete. They discuss the etiology, age and sex distribution, clinical findings, the localization of the lesion, and the anastomotic collateral circulation that develops. PMID- 6246635 TI - [Mastocytosis and leukemia (author's transl)]. AB - The authors report a case of Ph 1 positive chronic myelocytic leukemia associated with cutaneous mastocytosis, occuring lately in a 75 years old man. 12 similar cases (associations mastocytosis chronic or acute leukemia) are described in the literature. PMID- 6246636 TI - [Muscular metastasis, first symptom of bronchial carcinoma (author's transl)]. AB - One case of bronchial carcinoma in which a muscular metastasis was the presenting symptom is reported. Clinical features included pain and gradual swelling of left musculus supra-spinatus. Surgical biopsy showed intra-muscular metastasis of bronchial origin. Radiotherapy provided transient pain relief, but the patient died 15 months after the first symptoms. Metastatic tumors of skeletal muscles are found in some cases, when carefully searched for in routine autopsy surveys. Most of these tumors remain asymptomatic; in other cases clinical picture includes pain, swelling and diffuse or nodular induration of the involved muscles. Biopsy shows metastatic tumor in these muscles, which generally retains the same growth pattern as seen in the primary tumor. PMID- 6246637 TI - [The aged people in hospital. A case report (author's transl)]. AB - Agitated states in the elderly of varying aetiologies are encountered daily in medical practice. Of all medication available, that which gives the most constant and spectacular results is sulpiride at doses of 200 to 600 mg per day preferably by intramuscular injection, at least for initial treatment. PMID- 6246638 TI - [A further case of hepatocytic adenoma following oestrogenprogestogen treatment. Review of the literature (author's transl)]. AB - A young woman taking contraceptive hormone treatment for many years developed a hepatocytic adenoma discovered after a massive hemorrhage into the tumor. The patient recovered after a hepatectomy. A total of 160 such cases have been reported in the published literature, and recovery occurred after excision of the lesion in the majority of cases. Stopping the oestrogen-progestogen therapy seems to avoid recurrence but it is still not known whether this is sufficient to produce regression of a benign tumoral lesion. PMID- 6246639 TI - [Researches on the antiaggregative activity of Ginkgo biloba extract (author's transl)]. AB - Sodium lactate applied on the pia-mater of the rabbit induces the appearance of venous platelets thrombi. The same phenomenon occurs in the arteries after electric stimulation of the arterial wall. Gingo biloba extract, i.v. and per os, has been shown capable to partially antagonize these effects, particularly in the venous microcirculation. The ratio between the activity following the two modes of administration is about 1 to 5. PMID- 6246640 TI - Pathophysiologic considerations and clinicopathological correlates of technetium 99m stannous pyrophosphate myocardial scintigraphy. AB - 99mTc-PYP myocardial scintigrams represent a means to detect and localize acute myocardial necrosis. These scintigrams are expected to be abnormal with acute myocardial infarcts of at least 3 grams in weight if serial imaging is utilized and proper attention to technique is provided. Any etiology of myocardial necrosis may produce abnormal 99mTc-PYP scintigrams if the damage is relatively localized and includes at least 3 grams of tissue. It is possible to accurately size acute anterior and anterolateral transmural myocardial infarcts using area or 2 dimensional measurements. Further development in imaging cameras and computer techniques allowing three dimensional reconstruction of myocardial infarcts with this and similar imaging techniques may allow relatively precise quantitation of other types of myocardial infarcts. The "doughnut" and "persistently abnormal" 99mTc-PYP scintigrams appear to have anatomic and prognostic significance at least in subsets of patients studied, but larger numbers of individuals need to be evaluated before final conclusions regarding their ultimate prognostic significance can be reached. PMID- 6246641 TI - [Primary bronchopulmonary cancer]. PMID- 6246643 TI - Granular cell myoblastoma of the bronchus. AB - A granular cell myoblastoma of the bronchus occurring in a 20-year-old man was successfully treated by right lower lobectomy. His symptoms of chest pain and cough, the presence of an obstructing mass in a young patient, and the location of the lesion in a large bronchus on the right side are characteristic of this tumor. Electron microscopic examination of the tumor confirmed the diagnosis. PMID- 6246642 TI - Prospective study of congenital cytomegalovirus infection. AB - The overall incidence of neonates with urinary cytomegalovirus (CMV) excretion was 0.9% of 954 tested. The incidence was twice as high in the lower as in the upper socioeconomic group (SEG). Mothers of infants with CMV infection in the lower SEG reported a greater number of chronic and gestational medical problems and showed a lower mean age than mothers of CMV-infected infants in the upper SEG. The mean age of mothers of CMV-infected infants was not significantly different from the respective control group in either upper or lower SEG. There was no impairment of immune responses in nine prospective or in two referred cases. Although eight of nine prospective cases might have been considered asymptomatic at birth, careful evaluation in the neonatal period showed significant growth inhibition in five, specific clinical changes in seven, and nonspecific clinical changes in all of the nine infants. Thus, "asymptomatic" neonates may demonstrate effects of the infection during the neonatal period. PMID- 6246644 TI - Pyomyositis diagnosed by radionuclide imaging and ultrasonography. PMID- 6246645 TI - Pseudomesotheliomatous carcinoma of the lung. PMID- 6246646 TI - Dexamethasone-inhibited pertechnetate uptake in metastatic carcinoma of the cerebellum. AB - Two sodium pertechnetate Tc 99m brain scans, done within several days of each other, demonstrated inhibition of pertechnetate localization in a cerebellar lesion after dexamethasone therapy for cerebral edema. The lesion, a metastasis from a bronchogenic mucinous adenocarcinoma, was clearly present in the first scan, which was done before treatment. PMID- 6246647 TI - [Metabolic and functional characteristics of the peripheral blood leukocytes in cholestasis of different etiology]. PMID- 6246648 TI - The effect of dimethyl sulfoxide on gray matter injury in experimental spinal cord trauma. AB - The possible effect of dimethyl sulfoxide upon the development of lesions in the gray matter after experimental spinal cord trauma has been investigated with the use of cytochrome oxidase assay and quantitative histologic measurement of total liquefaction necrosis. Observations were made in 17 unconditioned dogs receiving an impact trauma of 400 gm cm force. Experimental animals were given 2.5 gm/kg of dimethyl sulfoxide in 40% solution intravenously one hour prior to trauma, and control animals received a similar volume of saline. No reduction could be found in the degree of loss of cytochrome oxidase at one hour after trauma, nor in the extent of acute necrosis. A slight but non-significant increase in the amount of hemorrhage was noted in gray matter at the trauma site following treatment with dimethyl sulfoxide. The agent resulted in an increase in cytochrome oxidase activities in nontraumatized control gray matter. PMID- 6246649 TI - [Calcium-regulating systems and cyclic adenosine monophosphate in peptic ulcer]. PMID- 6246650 TI - [Intestinal bacteria and colonic neoplasms]. PMID- 6246652 TI - The effect of tetracosactrin and corticosteroids on platelet aggregation : an in vivo and in vitro study. PMID- 6246653 TI - Dense bodies and total calcium in human platelets following aspirin ingestion for a two-week period. PMID- 6246651 TI - Diagnostic and therapeutic implications of ectopic hormone production in small cell carcinoma of the lung. PMID- 6246654 TI - Interference of bromophenacyl bromide with platelet phospholipase A2 activity induced by thrombin and by the ionophore A23187. PMID- 6246655 TI - [Amidinopenicillins (mecillinam and pivmecillinam). A new group of beta-lactamate antibiotics]. PMID- 6246657 TI - Indirect fluorescence antibody studies of porcine cytomegalo virus infections in the Netherlands. AB - Sera from 683 pigs of 41 swine herds with clinical atrophic rhinitis (AR), from 477 pigs of 37 herds with no AR history, from 267 breeding sows and breeding boars for slaughtering, from 22 boars at an artificial insemination centre, and from 103 SPF pigs were tested for the presence of antibodies to porcine cytomegalo virus (PCMV). The herds examined were spread all over the Netherlands. For the presence of antibodies to PCMV the indirect fluorescence antibody test was used. To obtain the antigen, the PCMV had been grown in pig lung macrophage cultures in Petri dishes for 10--12 days. These macrophages were dropped into the wells of slides. The serum dilution 1:20 of all the 103 sera from SPF pigs were negative, but 93 per cent of the other sera were positive. No marked differences were found between swine herds with clinical atrophic rhinitis and herds with no AR history. The FA titres in both types of herds seem to be at a comparable level. PMID- 6246656 TI - Cyanides and their toxicity: a literature review. AB - Cyanide is a potent and rapidly-acting asphyxiant which prevents tissue utilization of oxygen by inhibition of the cellular respiratory enzyme, cytochrome oxidase. Inhalation or ingestion of cyanide produces reactions within a few seconds and death within minutes. Cyanide toxicity of dietary origin has been implicated in acute animal deaths and as major etiologic factors in toxic ataxic neuropathy in man and as a cause of vision failure in humans suffering from tobacco amblyopia and leber's hereditary optic atrophy. Diagnosis of cyanide toxicity may be confirmed by a variety of laboratory procedures, but accurate assay is essential for proper conclusions from analysis of animal tissues several hours after death or from human samples in instances of chronic dietary exposure. Biological detoxification of cyanide is available through several routes, and the application of sodium nitrite with sodium thiosulfate or administration of methylene blue are effective treatment procedure. The environmental availability of cyanide in its various forms necessitates an understanding of its pathophysiology and responsible management of hazardous situations. PMID- 6246658 TI - [Use of an indirect lymphographic method with 198Au in the diagnosis of actinomycosis of the lymph nodes]. PMID- 6246659 TI - [Sources of the herpes simplex virus in preschool children's collectives]. PMID- 6246661 TI - Synthesis of 24-dehydrocholecalciferol. PMID- 6246660 TI - Progesterone production by dispersed monkey (Macaca mulatta) luteal cells after exposure to trypsin. AB - In an attempt to justify use of trypsin to achieve more thorough dispersion of luteal cell clumps in vitro, progesterone (P) production by collagenase dispersed monkey luteal cells from the mid-luteal phase corpus luteum (CL) was examined in vitro either after 10 min, or continuous (3h) exposure to trypsin (TR). In the first experiment, cells were pre-incubated in TR, then incubated at 37 degrees C for 3h with human chorionic gonadotropin (hCG) after the addition of soybean trypsin inhibitor (STI). Pre-incubation of luteal cells with TR had no effect on the level of P production under basal conditions. Cells that were preincubated with TR responded to hCG stimulation with increased progesterone secretion (P less than 0.01) in a fashion similar to untreated cells. P production in response to hCG was independent of TR concentration over the range of 0.05% to 0.2% during the pre-incubation period. However, continuous exposure (3h) of cells to TR significantly depressed (P less than 0.01) basal P secretion and inhibited the response to hCG. We conclude that TR had no effect on the biopotency of hCG per se, but probably the over-exposure to TR had an adverse effect on the LH/hCG receptors. Addition of STI after a 10 min pre-incubation with TR, prevented these deliterious effects, thereby permitting the use of TR to improve the completeness of luteal cell dissociation. PMID- 6246662 TI - Studies on the mode of action of calciferol XXV. 1 alpha,25-dihydroxy-5,6-trans vitamin D3, the 5E-isomer of 1 alpha,25-dihydroxyvitamin D3. AB - A structural analog of 1 alpha,25-dihydroxyvitamin D3 has been examined for biological activity and its ability to interact with the 1 alpha,25 dihydroxyvitamin D3 receptor system from chick intestine. This steroid, 1 alpha,25-dihydroxy-5,6-trans-vitamin D3, is the 5E-isomer of the parent molecule which differs from that molecule only in the position of the exocyclic C-19 methylene group. This new compound allows for the first direct assessment of the relative contribution of this A-ring substituent to ligand-receptor interaction and biological activity. This analog was found to be 6--12% as biologically active as the parent hormone and 13% as effective in binding to the intestinal receptor. PMID- 6246663 TI - Effects of superoxide dismutase on cholesterol 7 alpha-hydroxylation in swine. AB - Effects of carbon monoxide, nitrogen, ferricytochrome c and p hydroxymercuribenzoate were studied on cholesterol 7 alpha-hydroxylase activity of swine hepatic microsomes. The results suggest that a microsomal electron transport system is involved in hepatic microsomal cholesterol 7 alpha hydroxylation in swine. Cholesterol 7 alpha-hydroxylation is inhibited by superoxide dismutase in the standard assay system containing a NADPH generating system. Superoxide dismutase also inhibited cholesterol 7 alpha-hydroxylation in the system where superoxides were generated by enzymatic or nonenzymatic means in the absence of NADPH-generating system. The current study suggests that superoxide anion may be an important factor in the cholesterol 7 alpha hydroxylation of swine. PMID- 6246664 TI - [Effect of vagotomy on glycogen content, succinate dehydrogenase, cytochrome-c oxidase and lactate dehydrogenase activities in myocardium in experimental aortostenosis]. AB - The glycogen contents, succinate dehydrogenase, cytochrome-c-oxidase and lactate dehydrogenase activities in tissues of cardiac left cavity of vagotomized and nonvagotomized rabbits were studied two days and two weeks after aortostenosis and false operation. It is established that in vagotimized rabbits the prolongation of the hyperfunction period causes a less pronounced decrease in the glycogen level and a higher level of the succinate dehydrogenase and cytochrome-c oxidase activities. A conclusion is drawn that heart hyperfunction under conditions of vagotomy is accompanied by a less pronounced inhibition of aerobic and insignificant intensification of anaerobic oxidation processes as compared to their changes in rabbits with the heart maintained innervation. PMID- 6246665 TI - [Syringoepithelioma of the pharynx]. PMID- 6246667 TI - [Cancer of the biliary tracts simulating gallstones]. PMID- 6246666 TI - [Skin symptom in different localizations of cancer in the breast]. AB - The relationship of malignant tumors with the subcutaneous fat and skin is dependent on the stage of the disease, localization and tumor structure. Positive skin symptom at the first stage was found in 54% of patients, at the second stage -78% and at the third stage--in 97,7% of patients. PMID- 6246668 TI - Feline rhinotracheitis-calici vaccine and feline rhinotracheitis-calici panleukopenia vaccine: field evaluation for safety. PMID- 6246669 TI - Protection of laying hens against infectious bronchitis with inactivated emulsion vaccines. AB - Commercially-reared laying chickens were challenged at 31 weeks of age with a virulent infectious bronchitis (IB) virus. They showed a sharp drop in egg production, despite having been vaccinated at four and eight weeks old with live attenuated IB vaccines to a recommended schedule. In contrast, similar birds that had been further immunised at point-of-lay with inactivated oil emulsion IB vaccine, or with a combined IB/Newcastle disease (ND) emulsion vaccine, showed no detectable fall in egg production after the same challenge. Unvaccinated susceptible specific pathogen-free birds challenged at the same time stopped laying almost completely. In the birds revaccinated with emulsion vaccine, measurement of haemagglutination inhibition antibody levels to IB showed their geometric mean titres to be raised from less than 5 log2 at the time of vaccination to over 10 log2 four weeks later. Their antibody levels did not rise further followining the IB challenge whereas in the birds that had not been revaccinated antibody rises to nearly 10 log2 were detected after the same challenge. For pullets vaccinated earlier with live IB vaccine, revaccination with inactivated IB or IB/ND oil emulsion vaccine at point-of-lay provides a safe and effective way of protecting their egg production against IB infection. PMID- 6246670 TI - EHV1 and equine paresis. PMID- 6246671 TI - Viruses and diarrhoea in dogs. PMID- 6246672 TI - Aujeszky's disease control. PMID- 6246673 TI - [Determination of the resistance of hens to oncornaviruses]. PMID- 6246674 TI - [Comparative study of the biological properties of saponins]. PMID- 6246675 TI - [Diagnosis of Gumboro disease]. PMID- 6246676 TI - [Cell culture of the canine palatine tonsils]. PMID- 6246677 TI - [Treatment of cows for afterbirth retention]. PMID- 6246678 TI - The relationship between Sendai virus envelope antigens and the immune response in the presence and absence of ceruloplasmin. AB - The immune response of rabbits inoculated with different Sendai virus glycoprotein antigens depends on the structural identity of the protein support as well as on the mode of organization and structural homogeneity of the solubilized virus envelope. Incubation of the antigens with ceruloplasmin leads to modifications in the immune response, owing to the interaction with the active hemagglutinating and enzymatic sites. PMID- 6246679 TI - Herpesvirus in thin sections of formalin-fixed ground squirrel kidney tissue. PMID- 6246680 TI - Neutralizing serum antibodies to SV40 in blood donors. PMID- 6246681 TI - Coxsackie B2 virus isolation from a case of postnatal meningoencephalitis. AB - Clinical, morphopathological and virological data are presented with reference to a fatal case of postnatal meningoencephalitis from which a Coxsackie B2 virus strain could be isolated. The lesions consisted mainly in a meningeal inflammatory process with fibrocytes, a few lymphocytes and rare polynuclear cells. Marked stasis, diffuse and perivascular infiltrates with lymphcoytes and polynuclear cells, as well as lympho-glial nodules were observed in the brain parenchyma. PMID- 6246682 TI - [Radioisotope scanning in the diagnosis of pancreatic diseases]. PMID- 6246683 TI - The clinical physiology of water metabolism. Part III: The water depletion (hyperosmolar) and water excess (hyposmolar) syndromes. AB - Hyperosmolality occurs when there are defects in the two major homeostatic mechanisms required for water balance-thirst and arginine vasopressin (AVP) release. In this situation hypotonic fluids are lost in substantial quantities causing depletion of both intracellular and extracellular fluid compartments. Patients with essential hypernatremia have defective osmotically stimulated AVP release and thirst but may have intact mechanisms for AVP release following hypovolemia. Hyperosmolality can also be seen in circumstances in which impermeable solutes are present in excessive quantities in extracellular fluid. Under these conditions there is cellular dehydration and the serum sodium may actually be reduced by water drawn out of cells along an osmotic gradient. Hyposmolality and hyponatremia may be seen in a variety of clinical conditions. Salt depletion, states in which edema occurs and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) may all produce severe dilution of body fluids resulting in serious neurologic disturbances. The differential diagnosis of these states is greatly facilitated by careful clinical assessment of extracellular fluid volume and by determination of urine sodium concentration. Treatment of the hyposmolar syndromes is contingent on the pathophysiology of the underlying disorder; hyponatremia due to salt depletion is treated with infusions of isotonic saline whereas mild hyponatremia in cirrhosis and ascites is best treated with water restriction. Severe symptomatic hyponatremia due to SIADH is treated with hypertonic saline therapy, sometimes in association with intravenous administration of furosemide. Less severe, chronic cases may be treated with dichlormethyltetracycline which blocks the action of AVP on the collecting duct. PMID- 6246684 TI - [Evaluation of immune- and mediatormechanisms in experimental lung allotransplant rejection in recipients with and without preimmunisation (author's transl)]. AB - The present study is concerned with immune and mediator mechanisms following experimental lung allotransplantation. The investigations focused on the first set and--following allogenic preimmunisation--second set immune response in untreated as well as immunosuppressively treated recipients. After description of operation procedure and monitoring the hyperacute rejection process occurring in the immunized lung graft recipients was analysed. First, kinetic phenomena of antibody rejection and mediator consumption were investigated, thereafter the rejection within the graft was proved by immunological and biochemical methods. The immuno process was controlled by registration of cytotoxic and donor-organ binding antibodies in blood circulation and eluates of rejected lungs. Characterization of mediator mechanisms included alterations in complement-, coagulation-, and fibrinolytic system as well as in collagenolytic activity. Furthermore the effects of activated mediators on blood cells were proved and the findings were correlated with the functional and histomorphological substrates. Comparing hyperacute lung transplant rejection with that of other organ grafts a divergent participation of secondarily activated mediators, especially fibrinolysis, in reaction could be found. Following characterization of second set immune reaction the second part of the study was concerned with the primary immune response against lung allotransplants. Within this part especially the immunizing effect concerning humoral as well as cellular immunity was described and the influences of an immunosuppressive therapy were investigated. Beside of the control of donor-lung-binding antibodies in blood circulation and in eluates, the specifically immunized cells could be proved by a rosette forming cell-test using donor lung antigen coupled erythrocytes. These tests also were judged concerning their clinical-prognostic values. Basing on these results it was possible to comment specifically on important questions in lung allotransplant rejection. PMID- 6246685 TI - Exotic viral diseases. AB - Marburg virus disease, Lassa fever, monkeypox, and Ebola virus diseases of humans have all been recognized since 1967. These are examples of some of the exotic virus diseases which through importation may present a potential public health problem in the United States. Some of these viruses are also highly hazardous to laboratory and medical personnel. This paper is a review of the general characteristics, the epidemiology, and laboratory diagnosis of the exotic viruses which have been described during the last 25 years. PMID- 6246686 TI - Herpes simplex virus infection: problems and prospects as perceived by a peripatetic pediatrician. AB - The multivaried aspects of the herpes simplex viruses (HSV) types 1 and 2 and the infections they produce are discussed. Points emphasized are: (1) the need for considering these (and other viruses) from an evolutionary perspective; (2) the necessity of disseminating current methods for virus identification; (3) the great progress in molecular-virological aspects and in the genetics of the virus which provide new tools for epidemiological and immunological studies and define more convincingly the possible causal role of HSV-2 in cervical carcinogenesis; (4) the problems with vaccines and the therapeutic advances and failures; (5) the great psychosocial aspect of some herpetic infections and the need to be sympathetic and supportive to afflicted patients and their families; (6) the overreaction regarding HSV that currently exists among physicians, nurses, the public, and the press resulting in increased misery for those afflicted or misdiagnosed, or in poor advice or management given by some physicians pressured in part by the fear of malpractice suits. The problems then are many but the prospects for their solution are in sight as more research at all levels is being conducted today in all corners of the world on the complex herpes simplex viruses. PMID- 6246687 TI - Molecular epidemiology of DNA viruses: applications of restriction endonuclease cleavage site analysis. AB - Restriction endonucleases which cleave DNA at specific nucleotide sequences can be used to produce a set of DNA fragments of a viral genome which, when separated by gel electrophoresis, gives a characteristic "fingerprint" for that virus genome. This simple technique has been used to identify and classify DNA viruses of the herpes, adeno, and papova virus groups. Small variants within a given type (e.g., herpes simplex type I) are genetically stable and permit study and identification of individual strains of viruses. Such analyses have recently been applied to study the epidemiology of some DNA virus outbreaks. Restriction endonuclease fingerprinting provides a useful addition to methods for virus identification and classification. PMID- 6246689 TI - [Quantitative immunological method for determining rubredoxin in crude extracts of Acinetobacter calcoaceticus]. PMID- 6246688 TI - Hepatitis viruses: characterization and diagnostic techniques. AB - Two human hypatitis viruses have been identified and characterized, but one or more additional agents exist. Hepatitis B virus (HBV) is a complex 42-nm predominantly double-stranded DNA virus with distinct surface and core antigens and an endogenous DNA polymerase. Hepatitis A virus (HAV) is a 27-nm RNA virus with enterovirus-like properties. Progressively more sensitive and specific immunologic assays have been applied to the study of viral hepatitis and are available for routine diagnostic purposes. As a result we recognize distinct serologic response patterns to infection, new antigenic markers, biochemical biophysical characteristics of the viruses, and their epidemiologic features. Recombinant DNA technology has permitted the cloning of HBV genetic material and gene products in E. coli, but the virus has not been cultivated in vitro. In contrast, successful in vitro cultivation of HAV has finally been accomplished. Application of sensitive serologic tests for HAV and HBV has revealed that "non A, non-B" agents account for a substantial proportion of transfusion-associated hepatitis as well as hepatitis occurring in the absence of percutaneous exposure. These agents have been transmitted to chimpanzees, and several putative virus antigen-antibody systems have been described; however, a specific association between these virus antigens and non-A, non-B hepatitis has not been established. PMID- 6246690 TI - Diagnosing viral and chlamydial infections by cell culture. PMID- 6246691 TI - Crystalloid immunoglobulin inclusions in chronic lymphocytic leukemia. PMID- 6246692 TI - [Effect of copperions on trypsin activity]. PMID- 6246693 TI - [Worldwide program to eliminate smallpox. VI. Problems and prospects for epidemiologic supervision following completion of the program to eliminate smallpox]. PMID- 6246694 TI - Mechanisms of arrhythmias and of antiarrythmic activity, with special reference to mexiletine. PMID- 6246695 TI - The rise of plasma ACTH induced by ether is mediated through neural pathways entering the medial basal hypothalamus. AB - The effect of ether stress on the release of immunoreactive ACTH was studied in rats with an antero-lateral cut around the medial basal hypothalamus. Ether failed to raise the plasma ACTH level of rats in which an antero-lateral hypothalamic cut and adrenalectomy had been performed 7 to 8 days previously. Plasma ACTH was also unchanged in rats exposed to ether 2 h after an antero lateral cut. These data suggest that intact neural pathways entering the medial basal hypothalamus from the antero-lateral direction are necessary for the ACTH releasing action of ether stress. PMID- 6246696 TI - Uptake of T3 receptor complex by liver cell nuclei in vitro. PMID- 6246697 TI - The effect of galactose oxidase treatment on the hepatic binding and biological activity of desialylated human chorionic gonadotrophin. AB - 125I labelled desialylated hCG (asialo-hCG) was treated with galactose oxidase, in order to find out whether oxidation of the terminal galactosyl residues would diminish the hepatic uptake of asialo-hCG. Specific binding to the hepatic asialo glycoprotein receptor was monitored in vitro by a rat liver radioligand receptor assay (RRA). Hormonal activities were compared by ovarian RRA and by in vitro bioassay. Uptake studies were done in superovulated immature rats. Galactose oxidase treatment had hardly any influence on the in vitro ovarian binding and biological activity of [125I]asialo-hCG. Binding in the liver RRA was virtually abolished. In vivo hepatic uptake, however, was considerably above the level of [125I]hCG, as was the uptake in the kidneys. The hepatic uptake was inhibited by the administration of a high dose of asialo-fetuin. It is concluded that oxidation of the terminal galactosyl residues reduces the binding of asialo-hCG to the hepatic asialo-glycoprotein receptor, without affecting its hormonal properties. The ovarian uptake in vivo, however, is still limited by the high hepatic and renal clearance. PMID- 6246698 TI - A comparative study of the action of several lutropin derivatives on rat Leydig cells. AB - Rat intestinal cells prepared from testes were incubated in the presence of different lutropin derivatives obtained by chemical modification of the amino groups. The cAMP accumulation and the testosterone biosynthesis were determined in the cell homogenates. Binding determinations were carried out by a radioligand receptor assay using tritiated methylated lutropin. The binding activities- relative to native LH--of three different derivatives obtained by reductive alkylation (methylated, ethylated and isopropylated LH) were in good agreement with the relative potencies assessed by their capacity to stimulate cAMP and testosterone production. Guanidinated LH (11-NH2 groups modified) exhibited a binding activity and a relative potency relatively high with regard to cAMP accumulation (as compared with that of native LH). Its steroidogenic potency, however, was very low. When Leydig cells were incubated in the presence of native and guanidinated LH, the testosterone production was similar to that induced by the derivative alone, indicating that the derivative exerted a competitive inhibitory action preventing the stimulation of steroidogenesis by native LH. These results suggest that a guanidinated derivative is able to bind to the LH receptor and the complex so formed is able to be coupled with an adenylate cyclase pool (or cAMP compartment) which is not connected with the steroidogenic pathway. PMID- 6246699 TI - Panhypopituitarism secondary to head trauma: evidence for a hypothalamic origin of the deficit. AB - A complete endocrinological exploration was performed in a 23 year old male patient who presented clinical signs of an acquired panhypopituitarism which appeared two months after a severe head trauma, in order to determine whether the deficit lay in the hypothalamus or in the pituitary. TSH had normal basal levels, but presented a delayed rise after TRH administration. PRL rose normally after TRH administration, but presented a blunted response to both metoclopramide and insulin tolerance test. Cortisol rose significatively after lysine vasopressin, but failed to rise during insulin hypoglycaemia. These results are consistent with a hypothalamic defect. Extensive endocrinological data are often lacking in the few similar cases reported in the literature. Prl and TSH were usually found to have normal basal levels while other pituitary hormones were profoundly lowered. This was interpretated as a pituitary defect with some intact areas of the anterior lobe. However, this may also suggest a hypothalamic defect which could have been assessed by mor discriminative tests. PMID- 6246700 TI - Somatomedin and analogues of cyclic AMP increase the number of cells synthesizing DNA in cartilage from hypophysectomized rats. AB - The effects of somatomedin and certain nucleotides on nuclear labelling of cartilage cells with [3H]thymidine were determined by autoradiography. Segments of costal cartilage from hypophysectomized rats were incubated for 24 h in a basal medium with or without additions and then pulsed for 2 h with [3H]thymidine in the basal medium. Both somatomedin (0.1 U/ml) and Bt2cAMP (10(-4)M) increased the number of labelled nuclei, and the combined effects were more than additive. A parallelism between the effects of these agents on nuclear labelling and their effects on total thymidine incorporation into DNA was demonstrated. The 8 bromated derivative of cAMP (10(-4)M) also enhanced chondrocyte nuclear labelling, but neither 8-Br-5'-AMP (10(-4)7) nor 8-Br-cGMP (10(-4)M) exhibited actions of the cAMP analogues. It is concluded that in cartilage obtained from hypophysectomized rats and incubated under the specified conditions (1) both somatomedin and cAMP analogues increase the number of cells synthesizing DNA as well as total thymidine incorporation into DNA, (2) the effects of the hormone and cyclic nucleotide in combination are synergistic, and (3) the increased incorporation of labelled thymidine into DNA reflects increased DNA synthesis and not merely an alteration of the specific activity of the intracellular thymidine nucleotide pool. PMID- 6246701 TI - Interaction between parathyroid hormone and prostaglandin E1 on cyclic AMP metabolism in rat kidney. AB - The interaction between parathyroid hormone (PTH) and prostaglandin E1 (PGE1) in influencing cyclic AMP metabolism in rat renal cortical tissue was examined. PTH and PGE1 stimulated additively the adenylate cyclase activity in the homogenate of the tissue. Both PTH and PGE1 enhanced the level of cyclic AMP in the incubated renal cortical tissue, but the effect of their simultaneous addition did not exceed the effect induced by PTH alone. Cyclic AMP accumulated in the incubation medium by stimulation by PTH was decreased by the simultaneous addition of PGE1. When the tissue was pre-incubated for 30 min with 2 to 10 microgram/ml of PGE1, the magnitude of the increase of cyclic AMP caused by PTH subsequently added was lessened. However, the response to PTH of adenylate cyclase preparation obtained from the homogenate of PGE1-pre-treated tissue was not decreased. When first PTH was added to the incubating renal cortical tissue, the subsequent addition of PGE1 accelerated the decrease of cyclic AMP content in the tissue and decreased the amount of cyclic AMP released from the tissue. The interaction of PTH and PGE1 on cyclic AMP metabolism in the renal cortical tissue was in contrast to that seen in newborn rat calvaria where PGE1 and PTH acted additively in enhancing the level of cyclic AMP. PMID- 6246702 TI - Hepatic metabolism of vitamin D3 in streptozotocin-induced diabetic rat. AB - The effect of streptozotocin-induced diabetes on the in vitro conversion of vitamin D3 to 25-hydroxy-vitamin D3 (25-OHD3) by isolated liver microsomes from rachitic rats was examined. Enzymic activity was significantly less than that observed in control animals (P less than 0.001). Administration of insulin restored activity almost to control values. These findings provide evidence that diabetes in this animal model produces alterations in the metabolism of vitamin D. PMID- 6246703 TI - Serum prolactin responses to metoclopramide in Cushing's syndrome and Nelson's syndrome. PMID- 6246704 TI - Effect of ACTH on the proliferative and secretory activities of the adrenal glomerulosa. PMID- 6246705 TI - Influence of epidural analgesia on the catecholamine and cyclic AMP responses to surgery. AB - The effects of neurogenic block on plasma concentrations of adrenaline, noradrenaline and cyclic AMP were studied. Eighteen patients were subjected to surgery of moderate or minor extent under enflurance anesthesia with or without epidural analgesia. The results show that adrenaline secretion during surgical stress is a response to neurogenic stimuli, since the increase found in patients subjected to hysterectomy under general anesthesia is blocked by the addition of epidural analgesia. Furthermore, plasma adrenaline after neurogenic block is comparable with adrenaline levels during minor surgical stress. The plasma noradrenaline concentration does not correlate with the extent of trauma. In contrast to adrenaline levels, noradrenaline concentrations varied insignificantly during and after surgery. However, the addition of epidural block induced a postoperative increase in noradrenaline apparently unrelated to changes in heart rate or blood pressure. Simultaneous measurements of the catecholamines and cyclic AMP indicate that adrenaline is of minor importance for plasma cyclic AMP in resting patients, whereas the increase in cyclic AMP elicited by surgery reflects adrenaline-stimulated beta-adrenergic activity. PMID- 6246706 TI - Differentiated care of hip fracture in the elderly. Mean hospital days and results of rehabilitation. AB - Two series of elderly patients with hip fracture were compared with regard to hospitalization time and social situation after discharge from hospital. Our series included 131 patients from 1966 with late weight-bearing and 362 patients from 1972--1973, mobilized with early weight-bearing. Approximately two-thirds of the patients came from their own homes and one-third from institutions. The mean hospital stay for patients discharged to their own homes was 7 weeks in 1966 and 3--4 weeks in 1972--1973. This decrease in hospitalization time did not cause any increase in the proportion of patients discharged to institutions. Thus, among patients admitted from their own homes 48 per cent of the survivors returned directly home in 1966, and 62 per cent in 1972--1973. As compared to the prefracture mobility, postoperative mobility at 2 weeks proved to be a better indicator of the patient's chances of returing home. This may be a helpful guide when planning the aftercare of these patients. PMID- 6246707 TI - Albright's hereditary osteodystrophy. AB - The authors observed different clinical forms of Albright's hereditary osteodystrophy in 4 members of a family (two sisters, their mother and the maternal grandfather). The sisters were affected by pseudohypoparathyroidism type I, the older manifested the hypocalcemic variety, the younger the normocalcemic variety; the mother and the grandfather presented only with short stature and subcutaneous calcifications. The variety of clinical and biochemical alterations observed in these 3 generations supports evidence that Albright's hereditary osteodystrophy has a broad spectrum and that distinctions between the various forms of pseudohypoparathyroidsim should not be rigidly considered. PMID- 6246708 TI - Enhanced renal tubular calcium reabsorption independent of parathormone activity, in children on long term anticonvulsant therapy. AB - A significant reduction in the urinary calcium-creatinine ratio, was found in thirty-four ambulatory epileptic children on long term anticonvulsant therapy, studied during wintertime. No significant difference in the urinary excretion of cyclic AMP, phosphate or amino-acids was observed when the study-group was compared to an age-matched control group. Serum calcium and phosphate values were normal, but a significant increment in alkaline phosphatase was noted. Since there was no evidence of hyperactivity of the parathormone, it is suggested that the enhanced renal tubular calcium reabsorption in children on long term anticonvulsant therapy is a nonparathormone mediated phenomenon, possibly compensating for reduced calcium absorption in the gastrointestinal tract. PMID- 6246709 TI - Inactivated poliovaccine: adverse reactions and antibody responses. AB - Adverse reactions and antbody responses after inactivated poliovaccine were studied in 380 children. Fever reaction (greater than or equal to 37.5 degree C rectally) was recorded in 14% of children after the first poliovirus vaccination and in 19% after the second. Restlessness was reported in 15% and 14% of the chidren. Fever reaction exceeding 38.5 degree C was seen in 5% of the vaccines. Before the first vaccination at the age of six month 29% of the 48 children had antibodies against poliovirus type 1 and 2 and 43% against type 3. The first vaccination induced no significant changes in antibody titers. After the second vaccination antibody responses were low and 35%, 9%, and 35% remained seronegative to types 1, 2 and 3, respectively. After the third vaccination at the age of two years the respective geometric mean titers were 1:67, 1:335 and 1:48. No measurable antibodies were found to type 1 in 23%, to type 2 in 2%, and to type 3 in 10%. Only one child was triplenegative. All seronegative children were revaccinated and in all vaccinees a seroconversion ocurred two weeks after the booster dose. The combination of inactivated poliovaccine to DPT (Diphtheria, Tetanus, Pertussis) vaccine induced no significant change in poliovirus antibodies or in adverse reactions. PMID- 6246710 TI - Para-influenza pneumonia in DiGeorge syndrome two years after thymic epithelial transplantation. AB - A patient with DiGeorge syndrome developed pneumonia caused by para-influenza virus type 3 two years after immunological reconstitution with foetal thymic eptihelium. There was a transient reduction of mitogen-induced lymphocyte transformation at the time of the pneumonia. Although she recovered from the pneumonia, brochitis persisted and the virus could still be isolated from her pharyngeal secretions 3 1/2 months later. PMID- 6246711 TI - Antibodies to cytomegalovirus among personnel at a children's hospital. AB - Among 161 individual personnel at Children's Hospital, serum complement fixing antibodies were found more frequently (77%) in those who were in close contact with the patients than (39%) in those with less contact. This difference was most pronounced in the young age group. Most (80%) of the personnel at an age of 30 years or older, were seropositive, The results indicate that young personnel, working in close contact with infants and children in hospital, are at great risk of acquring cytomegalovirus infection. Student nurses, being exposed to these patients only for a few weeks, also were at risk of being infected. Seronegative pregnant women, working in a children's hospital, should therefore take measures to protect themselves from close contact with the patients since virus excretion occurs frequently, even without clinical signs of CMV-infection. PMID- 6246712 TI - Binding of enterotoxin from Clostridium perfringens type A to liver cells in vivo and in vitro. The enterotoxin causes membrane leakage. AB - Enterotoxin from Clostridium perfringens was shown to retain its biological activity after labelling with 125I. When injected intravenously into mice and rats, most of the radioactivity in the organs was present in the form of intact toxin. Studies of the tissue distribution of labelled enterotoxin showed the largest amounts in the liver, where the activity reached a maximum 10--15 min after administration. The highest concentration per g tissue was found in liver and kidneys. The radioactivity was excreted in the urine as a mixture of intact labelled toxin and low molecular weight degradation products. In vitro studies with purified parenchymal liver cells showed rapid release of lactate dehydrogenase (LDH) during treatment with enterotoxin, thus indicating severe membrane damage. PMID- 6246713 TI - The effect of human milk fractions on rotavirus in relation to the secretory IgA content. AB - Human milk from healthy Norwegian women was fractionated by ammonium sulphate precipitation and gel filtration. The protein content, lactoferrin and secretory IgA were measured. Specific antirotavirus IgA, detected by indirect immunofluorescence was found in one out of five milk samples before fractionation, while a more concentrated immunoglobulin fraction from the other four milk samples contained such IgA. Before fractionation, 3 of 5 milk samples neutralized human rota-virus infection of LLC-MK2 cells, whereas concentrated, IgA-rich fractions of all 5 milk samples neutralized human rotavirus. Some fractions without detectable IgA also neutralized human rotavirus. This suggests that human milk contains rotavirus specific IgA as well as rotavirus neutralizing activity of non-immunoglobulin nature. PMID- 6246714 TI - Human T cell response to Herpes simplex virus antigen in vitro. AB - Herpes simplex virus type I antigen (HSV-Ag) added to T cells from individuals with clinical history of recurrent herpes labialis causes a proliferative response in vitro. This T cell response requires presensitization of the responding cell donor and will occur only in the presence of adherent cells (macrophages). The intensity of the response is closely related to the number of adherent cells present, being optimal at a ratio of 10:1 between T cells and adherent cells. Preliminary studies also indicate that the response to HVS-Ag is restricted by the HLA-D/DR determinants of the T cell donor. PMID- 6246715 TI - Macrophages and the synthesis of connective tissue components. AB - 1. Macrophage homogenate, added to the incubation medium of granulation tissue slices, decreases the incorporation of labelled proline to collagen and other proteins, to a greater extent in the presence of certain prostaglandins and in oxygen atmosphere, but to a lesser degree if serotonin and cyclic AMP are added. 2. Rheumatoid synovial fluid, connective tissue active peptide (CTAP) of Castor and an extract from CCl4-damaged liver stimulate collagen synthesis in the presence of macrophages. 3. Preparations from non-treated macrophages stimulate the incorporation of glucosamine to acid mucopolysaccharides, mainly hyaluronate. 4. In a developing rat granuloma, the formation of collagen was stimulated by homogenized macrophages and by macrophage culture medium, but especially by whole macrophages in the presence of SiO2. PMID- 6246716 TI - Dissociation by lithium of hormone-induced formation of cyclic AMP and release of glycerol in isolated rat fat cells. AB - It has been suggested that lithium exerts some of its pharmacological actions by inhibition of the membrane-bound enzyme adenylate cyclase. However, the relationship between the lithium inhibition of adenylate cyclase and the corresponding physiological parameters, e.g. lipolysis, has not been investigated. In the present study it was found that lithium inhibited both the norepinephrine-induced accumulation of cAMP and release of glycerol in isolated rat fat cells, but only in the lower dose range of norepinephrine. At maximally effective concentrations of norepinephrine, where in the presence of 40 mM of lithium the formation of cAMP was reduced by approximally 40%, lipolysis remained unaffected. The basal content of cAMP and the basal release of glycerol were not inhibited by lithium. In addition to the inhibitory effect of lithium, lithium was found to stimulate the release of glycerol. This stimulatory effect of lithium may be explained by a prevention by lithium of the feedback inhibition by free fatty acids of adenylate cyclase and/or triglyceride lipase, since it could be avoided by increasing the concentration of bovine serum albumin in the incubation medium. It is concluded that lithium by inhibition of hormone stimulated adenylate cyclase activity inhibits lipolysis only at submaximal hormone concentrations. This dissociation by lithium of cAMP accumulation and glycerol release may suggest that at least at high concentrations of norepinephrine cAMP-independent factors are involved in lipolysis. PMID- 6246718 TI - Firing behaviour in stochastic nerve membrane models with different pore densities. AB - A stochastic nerve membrane model with a two-state pore system was investigated by computer simulation in the uniform (space-clamped) case. The model was based upon the Hodgkin-Huxley equations for the giant axon in squid, but where both the maximal membrane conductances and the rate constants were changed systematically. This was done in order to simulate nerve membranes of small axons, where both of these parameters are smaller than in squid. It was found that the effects upon the firing behaviour due to a finite number of pores were not greatly affected by changes in these parameters. When the specific injected current was calculated relative to the maximal membrane conductances, the threshold for firing was increased somewhat, and the frequency-current relationship became slightly more linear when the maximal conductances (or pore density) were decreased, or the rate constants increased. In the discussion it is shown how the results obtained could be applied qualitatively to the firing behaviour of nerve cells, and that firing in small nerve cells should be significantly influenced by the stochastic effects of a finite number of pores. Gating currents were also discussed, and their effects were found to be insignificant in small nerve cells. PMID- 6246717 TI - Pancreatic secretion and cyclic AMP in pancreatic tissue after intravenous infusion of secretin and vasoactive intestinal peptide in cats. AB - This study demonstrates that secretin and vasoactive intestinal peptide increased dose-dependently pancreatic bicarbonate secretion and cyclic AMP content in pancreatic tissue homogenates in cats. It is concluded that both hormones may act on the same receptor site in the pancreas and that their action is based on stimulation of the adenylate cyclase-cyclic AMP system. PMID- 6246719 TI - Beta-adrenergic dilator interaction with the constrictor response in resistance vessels of skeletal muscle during hemorrhage. AB - A marked beta-adrenergic dilator interaction with the vasoconstrictor response in skeletal muscle during hemorrhage is described. The dilator influence corresponded to some 40% of the constrictor response both at mild and moderate as well as at large bleeding. In absolute resistance units, the beta-adrenergic dilator influence averaged no less than 14 mmHg/ml X min-1 X 100 g-1) at large bleeding (hemorrhagic hypotension of 50 mmHg). Comparison of the hemorrhage induced resistance effects in the autoperfused innervated muscle, in the autoperfused denervated muscle, and in the innervated muscle cross-circulated from a donor animal, showed that the beta-adrenergic dilator influence more or less completely was caused by blood-borne catecholamines, in all likelihood by adrenaline, which is known to be secreted in large amounts during hemorrhage. The described beta-adrenergic dilator mechanism may serve to maintain nutritional blood flow by counteracting the constrictor response. It deserves consideration also from the point of view that it obviously has to be taken into account for proper evaluation of other vascular control mechanisms brought into action in hemorrhage. PMID- 6246720 TI - Time course of adaptation to low intensity training in sedentary men: dissociation of central and local effects. AB - The oxygen transporting capacity and the metabolic capacity of the vastus lateralis muscle were followed in parallel in 9 sedentary, overweighted men during a low intensity training program. Measurements were made at 0, 3, 6, 9, 12 and 30 weeks. Maximal oxygen uptake increased in an approximately linear fashion during the first 12 weeks (11%), but decreased a little (3%) during the following 18 weeks. Mean body weight decreased 8% (7.4 kg) during the training. The distribution of muscle fibre types, including the subgroups of type II fibres, did not change. Muscle enzyme activities remained essentially unchanged during the training. It was concluded that "central" och "local" adaptation need not occur in parallel, and that the leg oxygen utilization capacity probably does not limit the whole body's maximal oxygen uptake. PMID- 6246721 TI - Connective tissue of "fast" and "slow" skeletal muscle in rats--effects of endurance training. AB - The connective tissue of two skeletal muscles having different contractile properties was investigated in trained and untrained rats. The animals to be trained were put to run on a treadmill 5 days a week for 4 weeks. The "slow" m. soleus (MS) showed higher malate dehydrogenase activity but lower lactate dehydrogenase activity compared to the "fast" m. rectus femoris (MRF). When whole muscles were taken into account, the concentrations of both hydroxyproline and hexosamines were higher for MS compared to MRF. In the middle section of MS there were more hexosamines than in that of MRF, but no similar difference existed in hydroxyproline. The histochemical staining of collagen, however, suggested that there is also more internal collagen for MS as against MRF. It can be supposed that collagen of MRF and MS is differently distributed in different muscle connective tissue components. Compared to MS, the solubility of collagen was higher in MRF, whereas no significant difference between the muscles existed in the prolyl hydroxylase activity. The concentrations of hydroxyproline and hexosamines or the solubility of collagen were not affected by the training given, but the activity of prolyl hydroxylase was increased in MS suggesting that the metabolism of collagen may be accelerated by physical training. PMID- 6246722 TI - On the mode of action of botulinum toxin. PMID- 6246723 TI - Angiography in angiomatous lesions of the gastrointestinal tract. AB - Twenty patients with various angiomatous lesions of the gastrointestinal tract, such as right-colon angiodysplasia and manifestations of Rendu-Osler-Weber disease and Klippel-Trenaunay syndrome are reported. During the past 15 years an increasing number of such lesions have been reported, diagnosed mainly by angiography. The major complication from these vascular lesions is bleeding. Angiography is the primary method for their detection because of their often small size and is a prerequisite before surgery when reason exists for anticipating an angiomatous lesion as the source of bleeding. However, in certain cases angiography will fail to demonstrate the vascular abnormality or its full extent. PMID- 6246724 TI - Complications from irradiation of carcinoma of the uterine cervix. AB - The types and frequency of complications in 2248 patients irradiated for carcinoma of the cervix using different techniques are reported. Proctitis was the most frequent complication. Severe complications, such as fistulas, ureteral stenosis with hydronephrosis, enterocolitis, sigmoiditis, intestinal obstruction and skin necrosis occurred in 81 patients (3.6%). Only 36 patients (1.6%) developed fistulas. PMID- 6246725 TI - Chromosome counts of 90Sr-induced osteosarcomas in mice. I. Transplanted tumour series. AB - From 90Sr-induced primary tumours, three transfer series were established by serial in vivo transplantation. Chromosome counts were obtained from 2 of the primary tumours and 284 transplanted tumours. The recording of abnormalities was limited to numerical chromosome deviations and the occurrence of metacentric configurations. By means of the serial tumour transplantation the numerical chromosome progression was also analysed. Though appearing at different stages of the tumour evolution, similarities in chromosome pattern were observed. PMID- 6246726 TI - Effect of syngeneic bone marrow and thymus cell transplantation to 90Sr irradiated mice. AB - Mice irradiated with 90Sr in doses of 14.8 and 25.9 kB/q/g body weight were given bone marrow or thymic cells intravenously at monthly intervals, or in single doses at 120 or 170 days after injection of 90Sr. At the low dose level a high incidence of lymphoreticular tumours in all cell treated groups occurred as compared with animals irradiated with 90Sr only. At the high dose level only the bone marrow transplanted group contracted a high incidence of lymphoreticular neoplasia. Furthermore, a somewhat decreased osteosarcoma incidence in the cell transplanted animals appeared to be indicated. However, the results obtained are inconsistent and difficult to evaluate. Therefore, it seems necessary to repeat the experiments, if more precise conclusions should be possible to draw. PMID- 6246727 TI - Laryngeal carcinoma. IV. Analysis of treatment results using the Cohen model. AB - Long term results, obtained in the treatment of 308 patients with laryngeal carcinoma are analysed with respect to local recurrence and complications. In this analysis the Cell Population Kinetic model, proposed by COHEN (1971) is used. The model for squamous cell carcinoma is found to be useful and in close agreement with observations of local recurrence, although a slight modification may be justified from the present data. No special model exists for late edema, but the model for late effects in the vascular stroma seems to be useful in this respect. Based on the model, a working hypothesis has been proposed, by which it is possible to predict the frequency of local recurrence and late edema. An optimum treatment schedule is calculated and converted to a split-course technique. PMID- 6246728 TI - Simple experimentally derived algorithm for computer calculated dose rates associated with 137Cs gynecologic insertions. AB - A simple mathematical algorithm is derived from experimental data for dose rates from 137Cs sources in a finite tissue equivalent medium corresponding to the female pelvis. An analytical expression for a point source of 137Cs along with a simple numerical integration routine allows for rapid as well as accurate dose rate calculations at points of interest for gynecologic insertions. When compared with theoretical models assuming an infinite unit density medium, the measured dose rates are found to be systematically lower at distances away from a single source; 5 per cent at 2 cm and 10 per cent at 7 cm along the transverse axis. Allowance in the program for print out of dose rates from individual sources to a given point and the feature of source strength modification allows for optimization in terms of increasing the difference in dose rate between reference treatment points and sensitive structures such as the bladder, rectum and colon. PMID- 6246729 TI - Computation of dose distributions for radioactive seed implants. AB - An interactive treatment planning program for the computation of dose distributions for 125I and 192Ir seed implants of up to 300 sources is described. The seed coordinates are entered using either the keyboard or a sonic digitizer from either orthogonal or stereo films. The program produces a dose matrix which can be displayed and plotted directly or combined with the putput of other treatment planning programs to provide composite plans for treatments using multiple modalities. Seeds of different activities can be combined within a single plan. The program uses two-letter mnemonics for specifying the available options, among which are commands for choosing standard antero-posterior, lateral, and transverse plans. PMID- 6246730 TI - Effects of washing on phytohemagglutinin responsiveness of lymphocytes from irradiated patients. AB - The peripheral lymphocytes from irradiated patients generally have a reduced capability to respond to phytohemagglutinin (PHA). Whether a relationship exists between PHA-responsiveness and chromosome aberration frequencies was examined by washing the lymphocytes with culture medium. The results indicate that the defect in lymphocyte activation in patients receiving radiation therapy was caused by some reversible changes in the lymphocyte membrane directly associated with radiation exposure rather than by a radiation induced suppressor substance secondarily acting on the lymphocyte membrane. PMID- 6246731 TI - Procedures in external radiation therapy dosimetry with electron and photon beams with maximum energies between 1 and 50 MeV. Recommendations by the Nordic Association of Clinical Physics (NACP). PMID- 6246732 TI - Primary glioblastoma multiforme of the cerebellum. A case report. AB - A case of glioblastoma multiforme arising in the right cerebellar hemisphere is reported. The clinical, pathological, and radiographic similarity of this entity to the supratentorial glioblastomas is emphasized. PMID- 6246733 TI - Receptors for neurotransmitters and peptide hormones. PMID- 6246734 TI - Modulation of the binding properties of muscarinic receptors: evidence for receptor-effector coupling. PMID- 6246735 TI - Neuroreceptors: an overview. PMID- 6246736 TI - Regulation of acetylcholine receptor phosphorylation. PMID- 6246737 TI - Effect of calmodulin on catecholamine-linked adenylate cyclase activity in rat striatum and cerebral cortex. PMID- 6246738 TI - GABA-modulin: a regulatory protein for GABA receptors. PMID- 6246739 TI - Regulation of neurotransmission through presynaptic receptors and other mechanisms: possible clinical relevance and therapeutic potential. PMID- 6246740 TI - Drug-induced alterations in neurotransmitter receptor binding and function. PMID- 6246741 TI - Differential effects of kainic acid on benzodiazepine receptors, GABA receptors, and GABA-modulin in the cerebellar cortex. PMID- 6246742 TI - Pharmacological and biochemical evidence for an interaction between the benzodiazepine and GABA receptors. PMID- 6246743 TI - Studies on benzodiazepine receptors. PMID- 6246744 TI - Multiple benzodiazepine receptor complexes: some benzodiazepine recognition sites are coupled to GABA receptors and ionophores. AB - Certain benzodiazepine receptors may be associated in different ways with GABA receptors and/or ion recognition sites, to yield multiple receptor complexes. The benzodiazepine recognition site may be the same in all of the complexes. The different elements of the complexes almost certainly interact allosterically (Fig. 5). Different benzodiazepine receptor complexes may mediate different pharmacological effects of these drugs. PMID- 6246745 TI - Benzodiazepine receptor: localization by photoaffinity labeling and isolation of a possible endogenous ligand. PMID- 6246746 TI - Two or more conformations of benzodiazepine receptors depending on GABA receptors and other variables. PMID- 6246747 TI - Opiate receptors: problems of definition and characterization. AB - Receptor binding analysis has a great potential in identifying the site of action of a particular drug and in structure-activity studies. However, since no functional response is measured, an intrinsic difficulty to overcome is in establishing the functional significance of drug binding data. The multiplicity of receptors and subreceptors has a correspondence in a multiplicity of binding sites. It is not trivial which radioactive ligand is used to characterize the sites, and it is suggested that several radioligands with different properties (agonists, antagonists etc.) are studied. Methods are described here that allow for the analysis of ligand selectivity between several sites and their relative regional distribution. When enough data have been accumulated it may be possible to attribute a functional correlate to the binding data. PMID- 6246749 TI - Association between enveloped viruses and host cell membranes: a specific case of ligand receptor interaction. PMID- 6246748 TI - Some aspects of opiate receptors. AB - There is accumulating evidence that the existence of various endorphins is parallelled by the existence of multiple opiate receptors for these different ligands. At present, it appears that opiate binding sites in the mouse vas deferens are specifically sensitive to enkephalins, while the receptors of the vas deferens of the rat are selectively sensitive to beta-endorphin. Although enkephalin is present in the guinea pig ileum, it is not yet known if there are other endogenous ligands that preferentially combine with the mu-receptors located in this tissue. We suggest that a preference of the particular opiate receptors for specific ligands with different properties (e.g., their different susceptibility to enzymatic degradation) could characterize these binding sites as receptors for either neurotransmitters or hormones. PMID- 6246750 TI - Receptor-mediated inhibitions of NG108-15 adenylate cyclase: essential role of Na+ and GTP. PMID- 6246751 TI - Significance of neuropeptides in the control of corticosterone receptor activity in rat brain. PMID- 6246752 TI - On the presence of receptors for ACTH neuropeptides in the brain. AB - There is considerable evidence, based on a variety of CNS effects and structure activity relations as well as on indirect receptor studies, for the presence of multiple binding sites for ACTH neuropeptides in the CNS. Mainly because of the very low effective CNS concentrations of these peptides, putative CNS receptors seem characterized by very high affinity and very low capacity. These properties interfere with the demonstration of such receptor sites by direct binding assays using 3H-peptides and seem to necessitate the use of labeled neuropeptides with considerably higher specific activities. PMID- 6246753 TI - Opiate and neuroleptic receptor alterations in human schizophrenic brain tissue. PMID- 6246754 TI - GABA receptor binding and endogenous inhibitors in normal human brain and Huntington's disease. PMID- 6246755 TI - Denervation supersensitivity and beta-adrenergic receptors as a function of age. AB - The density and ontogenetic development of beta-adrenergic receptors varies in the different brain areas. The density of receptors in pineal gland, which at maturity is the highest of the brain areas studied, increases rapidly soon after birth, whereas the density of beta-receptors in cerebellum does not increase from birth. This development of beta-receptors in pineal gland is temporally related to the development of the sensitivity of adenylate cyclase to norepinephrine. Preventing the sympathetic innervation to the pineal gland before it has ever been innervated does not impede development of beta-adrenergic receptors. That is, the beta-receptors can develop in the absence of sympathetic input to the gland. In fact, reducing sympathetic input, particularly after the receptors have developed, causes an increase in the number of beta-adrenergic receptors and a concomitant increase in the response of adenylate cyclase to norepinephrine. With advanced age the number of beta-adrenergic receptors declines in several areas of the brain. This reduction may explain the reduced ability of aged tissue to respond to adrenergic agonists. The mechanism for this decrease in beta adrenergic receptors with age may be related to a reduced ability of aged tissues to produce compensatory increases in their receptor density in the face of decreased sympathetic input. PMID- 6246756 TI - Receptors for insulin and insulin-like growth factors in disease. PMID- 6246757 TI - Regulation of rat liver plasma membrane and intracellular insulin binding sites during diabetes, liver regeneration, and hyperinsulinism: radiolabeled hormone binding and electron microscopic autoradiograph studies. PMID- 6246758 TI - Histochemistry of receptors. PMID- 6246759 TI - Receptors, innervation, and neurotransmitter release: microphysiology of chemical synapses. PMID- 6246760 TI - Competitive block and ion channel block as mechanisms of antagonist action on the skeletal muscle end-plate. PMID- 6246761 TI - Electrophysiological studies of the mode of action of GABA on vertebrate central neurons. PMID- 6246762 TI - Regulation of beta-adrenergic receptors by phospholipid methylation. PMID- 6246763 TI - Receptor modeling for anticonvulsant and convulsant drugs. PMID- 6246765 TI - Phenytoin: electrophysiological effects at the neuromuscular junction. PMID- 6246764 TI - Phenytoin: blockage of resting sodium channels. PMID- 6246766 TI - Phenytoin: biochemical membrane studies. PMID- 6246767 TI - Phenytoin: cyclic nucleotide regulation in the brain. PMID- 6246768 TI - Phenobarbital: introduction. PMID- 6246769 TI - Ionic conditions and membrane behavior. PMID- 6246770 TI - Hormones and epilepsy. PMID- 6246771 TI - Brain synaptosomes in epilepsy: organization of ionic channels and the Na+-K+ pump. PMID- 6246772 TI - Local analgesic effect of morphine on the hyperalgesia induced by cAMP, Ca2+, isoprenaline, and PGE2. PMID- 6246773 TI - Sympathetic nerve stimulation of the isolated rat heart: release of prostaglandin like substance and the inhibitory effect of prostacyclin on the output of [3H] norepinephrine. PMID- 6246774 TI - Aspects of prostaglandin action on autonomic neuroeffector transmission. PMID- 6246775 TI - Influence of prostacyclin on sympathetic neurotransmission in the feline intestinal vascular bed. PMID- 6246776 TI - Modulatory role of prostaglandins on cholinergic neurotransmission in the guinea pig ileum. PMID- 6246777 TI - The plasma membrane sodium pump, PGE2 release, and acidic phospholipid turnover in the guinea pig taenia coli. PMID- 6246778 TI - Effects of indomethacin on quantal acetylcholine release at the frog neuromuscular junction. PMID- 6246779 TI - A role for prostaglandins as mediators of alpha-adrenergic inhibition of the acute insulin response to glucose. PMID- 6246780 TI - Effects of arachidonic acid on the thyroid gland in vitro. PMID- 6246781 TI - Hormone receptor control of prostaglandin F2 alpha secretion by the ovine uterus. AB - The interaction of the ovarian steroid hormones (estrogen and progesterone) and the polypeptide hormone of posterior pituitary origin (oxytocin) appear to regulate the ovine estrous cycle by controlling production of the uterine luteolytic hormone PGF2 alpha. From our results, it appears that these steroid hormones may control PGF2 alpha release by regulating the availability of receptors for oxytocin in the endometrium, the primary site of PGF2 alpha production. Secondarily the ovarian steroid hormones may also regulate basal endogenous levels of oxytocin in the blood stream which may reinforce the luteolytic release of PGF2 alpha. Similar mechanisms may also be operative during the initiation of parturition in which steroid hormones, OT, and PGF2 alpha appear to play major roles (26). In addition to the known interdependence of steroid hormones and the gonadotropins (FSH, LH, and prolactin) required to initiate follicular growth, ovulation, and CL function, there appears to be a second interdependence required to terminate the ovarian cycle via the uterine luteolytic hormone PGF2 alpha, namely by the interaction between ovarian steroids and the posterior pituitary hormone, OT. Thus for both the initiation and termination of the ovarian cycle, there is evidence of a close interaction between the ovary and brain. PMID- 6246782 TI - Is vascular innervation a prerequisite for PG-induced luteolysis in the human corpus luteum? PMID- 6246783 TI - Catechol estrogens stimulate uterine prostaglandin production. PMID- 6246784 TI - Protection against topical damaging agents and stimulation of gastric nonparietal cell secretion by 16, 16-dimethyl PGE2. PMID- 6246785 TI - Activation of human colonic mucosal adenylate cyclase by prostaglandins. PMID- 6246786 TI - Prostaglandins and inflammation: receptor/cyclase coupling as an explanation of why PGEs and PGI2 inhibit functions of inflammatory cells. PMID- 6246787 TI - Prostaglandin E2 and prostacyclin elevate cyclic AMP levels in elicited populations of mouse peritoneal macrophages. PMID- 6246788 TI - Lysosomal enzyme release from human granulocytes is inhibited by indomethacin, ETYA, and BPB. PMID- 6246789 TI - Secretion of inflammatory mediators from synovial fibroblasts: dissociation of collagenase and prostaglandin release. PMID- 6246790 TI - PGE1 but not PGI2 desensitizes the PGI2 receptor-adenylate cyclase complex in human foreskin fibroblasts. AB - In intact cells or in membranes prepared from intact cells that were preincubated with PGE1, subsequent PGI2-stimulation is attenuated. Preincubation of cells with PGI2 does not induce desensitization of PGI2-stimulated adenylate cyclase. These data suggest that HFF cells must be constantly exposed to a biologically active prostaglandin for desensitization to occur. The intrinsic chemical lability of PGI2 may be a biochemical protection mechanism against desensitization in cells that normally respond to PGI2. PMID- 6246791 TI - Cyclic AMP and prostaglandins in periodontal disease. AB - Since inflamed gingiva contain significantly higher levels of endogenous PGs (8) and cAMP than normal gingiva and since exogenous PGs have been shown to stimulate endogenous cAMP synthesis in gingiva in vitro, we suggest that the increase in the endogenous cAMP levels found in the inflamed tissue may be attributable to the increase in endogenous PGs. Cyclic AMP has been reported to stabilize the lysosomal membranes of inflammatory cells; hence, the increase in cAMP formation in inflammation seems to be associated with an endogenous compensatory protective mechanism which is able to stop immune or allergic reactions (9, 10). PMID- 6246792 TI - Sarcomatous renal tumor of childhood. An electron microscopic study. AB - A review of 106 cases of Wilms' tumor revealed five examples of a distinctive, monomorphic, sarcomatous renal tumor. Electron microscopic studies suggested that such tumors have their origin from the blastemal cap cells of the developing metanephros. These variants of Wilms' tumor are more likely to metastasize to bone and have a poorer prognosis than the usual type of nephroblastoma. PMID- 6246793 TI - Heterogeneous morphologic features of plaques induced by five strains of human cytomegalovirus. AB - Five strains of human cytomegalovirus (CMV) were examined in three human fibroblastic cultural systems with respect to plaque size and morphologic features. Plaques produced in cultures of fibroblastic cells from thyroid, and to a lesser extent in those from human embryonic skin-muscle tissue, had strain associated morphologic differences that were stable on repetitive examination. The variations in morphologic characteristics of plaques appeared to reflect cytopathic changes, and the five strains could be separated on the basis of morphologic characteristics into two polar groups. Comparison of the sensitivities of three human fibroblastic cell lines for the detection of CMV revealed that one line was consistently inferior. PMID- 6246794 TI - Malignant mixed tumor of the gallbladder. AB - Multimorphic malignant tumors containing elements of two or more germ layers presenting as mixed tumors are rarely encountered in the gallbladder. A review of the literature revealed a report of a single case in which the histologic appearance was similar to that of the case reported herein. The malignant mixed tumor of the gallbladder appears to be a highly anaplastic and rapidly fatal neoplasm. It may be suspected by the presence of chondroid or myxoid tissue, or both, on gross examination. PMID- 6246795 TI - Phenotypic variation in a family with partial androgen insensitivity syndrome. AB - A family with partial androgen insensitivity syndrome exhibited considerable variation in phenotypic expression of their androgen resistance. One subject died at 2 1/2 years of age of a Wilms' tumor. In the two living members, one had a micropenis with otherwise normal genitalia, while the other had a small phallus, perineoscrotal hypospadias, bifid scrotum, and persistence of a vaginoutricular pouch. At puberty, plasma androgens and serum gonadotropins increased to normal or elevated values. However, despite adequate endogenous plasma testosterone levels and testosterone therapy, these patients showed poor virilization and were sterile. Studies of cultured sexual skin fibroblasts showed adequate 5 alpha reductase activity and normal receptor affinity and capacity for dihydrotestosterone. An X-linked mode of inheritance is postulated, although autosomal dominance cannot be ruled out. PMID- 6246796 TI - Disseminated cytomegalovirus infection with gastrointestinal involvement. The role of altered immunity in the elderly. AB - Disseminated cytomegalovirus (CMV) infections seem to occur in patients with impaired immunity. The evidence for the altered immunity and the predisposing factors in elderly patients are summarized and illustrated by a report of a 75 year old patient with CMV colitis. The clinical and pathologic features of CMV infections involving the gastrointestinal tract in noncompromised hosts are reviewed. PMID- 6246797 TI - General comments on the study on the efficacy of nosocomial infection control (SENIC Project). PMID- 6246798 TI - The SENIC Project. Study on the efficacy of nosocomial infection control (SENIC Project). Summary of study design. AB - With the emergence of nosocomial infections as a serious problem among US hospitals, the Center for Disease Control undertook in 1974 a nationwide study to evaluate approaches to infection control. The three-phased project, now known as the Study on the Efficacy of Nosocomial Infection Control, or SENIC Project, was designed with three primary objectives: 1) to determine whether (and, if so, to what degree) the implementation of infection surveillance and control programs (ISCPs) has lowered the rate ofnosocomi al infection, 2) to describe the current status of ISCPs and infection rates, and 3) to demonstrate the relationships among characteristics of hospitals and patients, components of ISCPs, and changes in the infection rate. With data collection completed in a nationally representative sample of hospitals, analysis is underway to identify approaches to infection control that are most effective for the least cost to hospitals and to point out additional specific questions to be answered by future research. PMID- 6246799 TI - Adenovirus infection in the immunocompromised patient. AB - Illness associated adenovirus infection is described in 15 immunocompromised patients. Patients were immunocompromised by severe underlying disease, immunosuppressive or corticosteroid therapy or by age (prematurity). Evidence of adenovirus infection was obtained by either viral isolation or, in two cases, characteristic adenovirus inclusion bodies at postmortem study. All clinical illness was associated with high fever (temperature greater than 39 degrees C). Eighty per cent of the patients had severe systemic complaints including malaise, lethargy, fatigue and night sweats; a similar number of gastrointestinal symptoms. Pulmonary complaints were described in 11 of 15 cases and included cough (67 per cent) and tachypnea (53 per cent). Roentgenologic evidence of pneumonia was demonstrated in 12 of 15 patients (80 per cent). Elevation of serum hepatic enzyme levels (serum glutamic pyruvic transaminase (SGPT)) occurred in eight of 11 patients (73 per cent) and was moderate to severe (serum glutamic pyruvic transaminase greater than 450 IU/liter) in five of 11 (45 per cent). Nine patients died; seven after a rapid downhill course and two after a prolonged illness. Evidence of adenovirus infection microscopically by autopsy in the lung, liver or both is demonstrated in four patients with fulminant systemic illness. Adenovirus infection should be considered in the etiology of severe overwhelming illness in the immunocompromised host. PMID- 6246800 TI - Skeletal responsiveness in pseudohypoparathyroidism. A spectrum of clinical disease. AB - Three cases of pseudohypoparathyroidism with roentgenographic evidence of hyperparathyroid bone disease are described. Renal resistance to exogenous parathyroid hormone (PTH), the hallmark of pseudohypoparathyroidism, was documented by markedly blunted or absent urinary phosphate and cyclic AMP responses to parathyroid extract. At the time of diagnosis all patients were hypocalcemic and hyperphosphatemic with elevated serum alkaline phosphatase levels and subperiosteal resorption noted on skeletal films. Bone biopsy in one patient revealed a histologic appearance consistent with hyperparathyroidism. Serum PTH levels, measured in two patients while they were hypocalcemic, were elevated. None of the patients had short stature, brachydactyly, subcutaneous calcification or mental deficiency. These cases are compared to the 15 well documented cases previously reported. The presently available information on pseudohypoparathyroidism indicates a variable skeletal response to PTH mediated by several factors extrinsic to bone and suggests that pseudohypoparathyroidism with hyperparathyroid bone disease is one extreme of a clinical spectrum of skeletal responsiveness to PTH. This disorder is part of an expanding clinical picture which makes pseudohypoparathyroidism a diagnostic consideration in any patient with unexplained hypocalcemia, hyperphosphatemia, elevated alkaline phosphatase levels or metabolic bone disease. PMID- 6246802 TI - Chromosomes, embryonal tumors, and birth defects. PMID- 6246801 TI - Environmental pollution and pregnancy: risks and uncertainties for the fetus and infant. AB - Numerous environmental contaminants can affect the developing embryo, fetus, or infant. This essay explores such questions as these: What is the importance in mutagenesis and teratogenesis of macroenvironmental pollutants such as the heavy metals, dioxin derivatives, polychlorinated diphenyl compounds, and pesticides? What is the significance of microenvironmental pollutants (or social environmental factors) such as tobacco smoke, alcohol, and pharmacologic agents over which exposed individuals have considerable control? What are some of the ethical and legal implications of these toxins of which clinicians should be aware? PMID- 6246803 TI - Enhancement of allergic encephalomyelitis by particulate adjuvants inoculated long before antigen. AB - Carbonyl iron and several other particulate materials have been reported to enhance the development of experimental allergic encephalomyelitis when injected with neural antigen. In the present work, silicon and silica powders have been added to the list of particulate adjuvants. In addition, several particulate materials, but not carbonyl iron, were effective adjuvants when inoculated four weeks or even six months before the neural antigen. It was necessary for adjuvant and antigen to be injected in the same region, but both intraperitoneal and subcutaneous routes were effective. The long-lasting adjuvanticity of certain particulates in the tissues is probably related to their bland and unabsorbable nature. The reasons for restrictions in the range of adjuvants and antigens that are effective in this system and the possibility of a similar occurrence in nature remain to be investigated. PMID- 6246805 TI - Effects of vitamin D metabolites on bovine parathyroid hormone release in vitro. AB - We evaluated the effects of 1 alpha,25-dihydroxycholecalciferol (1,25(OH)2D3), 24R,25-dihydroxycholecalciferol (24,25(OH)2D3), and 25-hydroxycholecalciferol (25(OH)D3) on the release of parathyroid hormone (PTH). Bovine parathyroid tissues were incubated in vitro for 4 h in low-calcium (1.0 mM) medium. 1,25(OH)2D3 ((10(-9)-10(-12)M), 24,25(OH)2D3 (10(-6)-10(-8)M), and 25(OH)D3 (5 X 10(-7)-5 X 10(-9)M) inhibited PTH release. Inhibition by all metabolites was concentration and time dependent. On a molar basis, 1,25(OH)2D3 was the most potent metabolite, being at least 100 times more potent than 24,25(OH)2D3 and 25(OH)D3; 24,25(OH)2D3 was about 5 times more potent than 25(OH)D3 at concentrations producing 65% inhibition. Inhibition by high concentrations of metabolites was evident by 1 h of incubation; inhibition was progressive throughout incubation, and maximal suppression to 30-40% of control occurred during the fourth and final hour of incubation. 1,25(OH)2D3 (10(-11) M), a low concentration that did not inhibit secretion, transiently stimulated release. In conclusion, under conditions of low-calcium-stimulated PTH release, 1,25(OH)2D3, 24,25(OH)2D3, and 25(OH)D3 inhibited PTH release, 1,25(OH)2D3 was the most potent inhibitor. PMID- 6246804 TI - Pathology of the liver with bone marrow transplantation. Effects of busulfan, carmustine, acute graft-versus-host disease, and cytomegalovirus infection. AB - The morphologic changes in the livers of autopsy specimens from recipients of 62 allogeneic bone marrow transplants were reviewed and characterized in specimens from patients who had had apparent drug toxicity, graft-versus-host disease (GVHD), and disseminated cytomegalovirus (CMV) infection. Two conditioning protocols were associated with significant hepatic toxicity. Two of 3 recipients on whom autopsies were performed who had been prepared with high doses of carmustine, cyclophosphamide, and total body irradiation had undergone acute hepatic failure and submassive necrosis with periportal sparing. Seven of 9 patients prepared with busulfan (16 or 20 mg/kg) and cyclophosphamide had moderate to marked centrilobular sinusoidal fibrosis and associated hepatocellular atrophy and necrosis. Twenty of the patients had acute cutaneous GVHD with associated hepatic dysfunction, including 8 with disseminated CMV infection. Of the 12 patients without concomitant CMV infection, 5 had an early onset of GVHD and had predominantly periportal and focal midzonal hepatocellular necrosis, and 7 had acute GVHD with later onset with predominantly bile duct injury. Fifteen patients had evidence of disseminated CMV infection. Whereas CMV infection alone was associated with both hepatocellular and bile duct injury, detectable virus infection was not a requirement for hepatocellular or bile duct injury associated with GVHD. PMID- 6246806 TI - Protein kinase activity in isolated tubules of rat renal medulla. PMID- 6246808 TI - Effect of 1,25-(OH)2D3 on jejunal absorption of magnesium in patients with chronic renal disease. AB - These studies were performed to see if jejunal malabsorption of magnesium in patients with chronic renal disease was influenced by therapy with 1 alpha, 25 dihydroxyvitamin D3 [1,25-(OH)2D3; 2 microgram/day by mouth for 7 days]. This treatment restored normal serum concentrations of the vitamin D metabolite from 0.9 +/- 0.2 to 4.2 +/- 0.6 ng/dl. Jejunal absorption of magnesium, measured by a triple-lumen constant-perfusion technique, was enhanced in each of the seven patients by this therapy. The mean value rose from 0.04 +/- 0.02 to 0.13 +/- 0.02 mmol . 30 cm-1 . h-1. This last value is similar to the magnesium absorption rate in untreated normal subjects. These results demonstrate that magnesium absorption in the human jejunum is dependent on vitamin D, and they show that 1 alpha,25 dihydroxyvitamin D3 therapy in patients with chronic renal failure is associated with an enhanced jejunal absorption of magnesium. PMID- 6246809 TI - Effect of chemically defined diets on antral and serum gastrin levels in rats. AB - When rats were fed isocaloric amounts of chemically defined diets with variable amounts of protein (8-60%) or fat (0-30%) over a 10-day period, their serum and antral gastrin concentrations were, respectively, 60 and 40% lower than the levels of chow-fed rats. It was also determined that neither the low bulk content of these diets nor their inability to adequately buffer the gastric pH contributed to this response. The time course of this dietary-induced reduction in gastrin levels was investigated and it was found that the serum hormone levels were significantly reduced as early as 1-2 h after chow-fed rats were placed on these chemically defined diets. Antral gastrin levels were maintained at normal levels for 4-5 days after rats started consuming these synthetic diets and fell thereafter. With all of the chemically defined diets tested, the gastrin secretory response to a meal was significantly reduced. It therefore appears that synthetic diets lack some undefined food constituent present in chow that is required for the normal postprandial release of gastrin or, alternatively, that they contain an inhibitory factor which blocks the normal secretory response. PMID- 6246807 TI - Histamine responsiveness of isolated gastric glands. AB - Gastric glands isolated from rabbit were employed to perform a pharmacological characterization of the histamine receptor associated with physiological and biochemical responses in gastric cells. Five separate response parameters were characterized using histamine analogues and histamine antagonists. The following parameters were studied: respiration, accumulation of the weak base aminopyrine, adenylate cyclase activity, cAMP accumulation, and the uptake of histamine. All parameters were examined for agonist and antagonist potency using dose-response curves, ED50 and pA2 values. Comparison of the ED50-agonist and pA2-cimetidine values showed a remarkable similarity for respiration, aminopyrine accumulation, adenylate cyclase activity, and cAMP accumulation. The agonist potency sequence and pA2 values for H2- vs. H1-receptor antagonists characterized the histamine receptor associated with these four parameters as being of the H2 type. Moreover, the similarity of pharmacological characteristics provides evidence for a similar, if not common, receptor for these responses. The histamine uptake system shows a generally lower affinity for most agonists. Although the general agonist potency sequence is similar to the other parameters, notable exceptions were found for antagonists and the typical H2-agonist, dimaprit. Thus, the uptake system does not appear to be related directly to the activation of secretion and the carrier binding site cannot be simply defined by H1 or H2 properties. PMID- 6246810 TI - Dissociation of avian salt gland: separation procedures and characterization of dissociated cells. AB - A procedure for dissociation of the nasal salt glands of the domestic duck, Anas platyrhynchos, into suspensions of individual cells has been developed. This technique employs enzymatic digestion with collagenase, hyaluronidase, and chymotrypsin; divalent cation chelation with EDTA; and gentle mechanical dispersion. Average cellular yields of 39 and 26% based on DNA recovered were obtained from the glands of freshwater- and saline-adapted ducks, respectively. Epithelial secretory cells comprised 60-80% of the cell suspensions with the remainder of the populations consisting of endothelial cells, fibroblasts, and blood cells. The dissociated cells were viable as judged by trypan blue exclusion (80-100%, maintenance of ultrastructural integrity, and retention of responsiveness to secretagogues and metabolic inhibitors. Methacholine chloride (0.5 mM) stimulated oxygen consumption by suspensions of both freshwater- and saline-adapted cells, whereas ouabain (0.05 mM) abolished the methacholine stimulated respiratory response. These cell suspensions provide a promising system for the in vitro study of secretory mechanisms in the avian salt gland. PMID- 6246811 TI - Effects of thyroid hormone on UTP content and uridine kinase activity of rat heart and skeletal muscle. AB - In rats made hyperthyroid by daily intramuscular injections of 250 microgram thyroxine (T4)/100 g body wt for 5 days, uridine kinase activity of extracts of psoas and cardiac muscle was markedly increased Vmax of the enzyme was elevated with no change in the apparent Km for uridine. In animals treated as above, significant increases in UTP and total uracil nucleotide contents were observed in heart and skeletal muscle. Twelve hours after a single intraperitoneal injection of 30 microgram/100 g body wt of 3,5,3'-triiodothyronine (T3), cardiac uridine kinase was significantly increased. Brain uridine kinase was unaffected by thyroid hormone treatment. In thyroidectomized rats, uridine kinase activity was lower than normal. The effect of thyroidectomy on uridine kinase activity was overcome by daily subcutaneous injections of 3 microgram T4/100 g body wt for 7 days. The rise in cardiac uridine kinase activity produced by T3 could be prevented by prior administration of actinomycin D. PMID- 6246812 TI - Effects and interactions of 24R,25(OH)2D3 and 1,25(OH)2D3 on bone. AB - The effects of various combinations of therapy with 1 alpha,25 dihydroxycholecalciferol (1,25(OH)2D3) and 24R,25-dihydroxycholecalciferol (24R,25(OH)2D3) on structural and dynamic parameters of bone were evaluated in 40 chicks raised on a vitamin D-deficient diet from time of hatching and supplemented with the dihydroxylated metabolites. The results showed that: 1) the maintenance of volumetric density of bone is dependent on the presence of 1,25(OH)2D3, 2) lack of 1,25(OH)2D3 is associated with an increase in the number of osteocytes per unit volume of bone, most probably due to decreased amounts of bone formed by each osteoblast before becoming an osteocyte, 3) adequate quantities of either 24R,25(OH)2D3 or 1,25(OH)2D3 are needed to prevent accumulation of osteoid or the production of endosteal fibrosis, and 4) maintenance of normal tetracycline label width requires both hydroxylated compounds with one of them in sufficient amounts. The data of this study demonstrate that the integrity of certain parameters of bone structure could be maintained only with 1,25(OH)2D3, others with either dihydroxylated metabolites, and still others with a combination of both. These data underscore the biological activity of 24R,25(OH)2D3 by demonstrating its effectiveness on bone. PMID- 6246813 TI - Renal potassium adaptation: Na-K-ATPase activity along the nephron after chronic potassium loading. AB - To identify nephron sites where renal potassium adaptation takes place, Na-K ATPase was measured with a micromethod along the nephron of potassium-loaded mice. A possible role of aldosterone in this process was evaluated in K-loaded animals treated concurrently with pharmacologic doses of spironolactone. Animals fed a potassium-enriched diet for at least 2 wk excreted about 90% of ingested potassium in the urine, and fractional potassium clearance averaged 87 +/- 8%, compared with 13 +/- 2% in controls. Na-K-ATPase activity per millimeter tubule length increased by 225% in the cortical collecting tubule and by 177% in the medullary collecting tubule, but was not substantially affected in other nephron segments. Stimulation of Na-K-ATPase was identical in the cortical collecting tubule of K-loaded mice treated with spironolactone. These results indicate that chronic potassium loading in the mouse results in an adaptive increase potassium loading in the mouse results in an adaptive increase in Na-K-ATPase in the collecting tubule and suggest that this nephron segment is the major site of potassium adaptation in this species. This effect appears to be independent of aldosterone. PMID- 6246814 TI - Effect of ouabain and potassium on ion concentrations in the choroidal epithelium. PMID- 6246815 TI - Dietary manipulation of age-related decline in vascular smooth muscle function. PMID- 6246816 TI - Effects of coronary artery occlusion on thoracic spinal neurons receiving viscerosomatic inputs. AB - Action potentials of single cells in the gray matter of the T2 to T4 spinal segments of chloralose-anesthetized cats were recorded during occlusion of the anterior descending branch of the left coronary artery. Only cells responding both to visceral and somatic afferent inputs were examined. In 53% of the cells the discharge frequency was unaffected by coronary artery occlusion (CAO). The remaining 47% could be classified by four response patterns: 1) in 18% frequency increased immediately following the onset of CAO; 2) in 22%, frequency increased 13.6 +/- 3.3 (SE) s after CAO and the increased frequency usually was associated with changes in the configuration of the electrocardiogram; 3) in 3%, frequency increased at the onset of CAO and then increased more approximately 11 s later; 4) in 4%, inhibition of spontaneous activity occurred during CAO. A noxious pinch applied to the somatic receptive field maximally excited 94% and inhibited 6% of the cells. Since viscerosomatic convergence provides a basis for referred pain, these cells could potentially be involved with transmission of nociceptive information to regions of the brain that integrate pain sensations. PMID- 6246817 TI - Age-related differences in angiotensin I metabolism by isolated perfused rat lungs. AB - The pulmonary vasculature has been implicated in the clearance of several vasoactive substances from the circulation including angiotensin I (AI). In view of the previously reported age-related differences in angiotensin-converting enzyme (ACE) activity of lung homogenates, it was of interest to examine the ability of intact perfused lungs to metabolize AI. Lungs from newborn and adult rats were perfused with Krebs bicarbonate buffer containing 1.0 ng/ml AI in a single-pass, nonrecirculating system. The rate of perfusion was normalized to lung mass. Removal of AI was determined from the transpulmonary difference in radioimmunoassayable AI. Lungs from 7-day-old rats removed a smaller fraction of AI from the circulation than did adult lungs. The age-related increase in AI clearance was accompanied by an increase in pulmonary ACE content; however, enzyme content alone could not account for the observed differences. The increased metabolism of AI by the pulmonary vasculature during development may contribute to the age-related increase in circulating angiotensin II concentrations. PMID- 6246818 TI - Postnatal development of the renin-angiotensin system in rats. AB - The purpose of this investigation was to correlate the development of the various enzyme activities associated with the renin-angiotensin system with age-related differences in the steady-state concentrations of angiotensin I (AI) and II (AII). Angiotensin was quantified by radioimmunoassay. Plasma renin activity and concentration increased between birth and 3 wk of age, and declined thereafter to adult values. Renal renin content, on the other hand, increased throughout the first 6 wk of postnatal life. The concentration of AII in plasma also increased following birth; however, maximum concentrations were not attained until 5 wk of age. In contrast, plasma AI did not increase between 3 and 6 wk of age. These data suggest that the steady-state concentration of AII in neonatal rat plasma may be partially limited by the low plasma renin substrate concentration. The increase in AII between 3 and 6 wk of age may reflect the increasing converting enzyme activity. PMID- 6246819 TI - Malignant mesenchymal nephroma of infancy: report of a case with pulmonary metastases. PMID- 6246820 TI - Tubular carcinoma of the breast. PMID- 6246821 TI - Bronchio-alveolar carcinoma. PMID- 6246822 TI - Pauses at positions of secondary structure during in vitro replication of single stranded fd bacteriophage DNA by T4 DNA polymerase. PMID- 6246823 TI - Enzymatic microassay of serum bile acids: increased sensitivity with an enzyme amplification technique. PMID- 6246824 TI - A modified method for amino acid analysis with ninhydrin of Coomassie-stained proteins from polyacrylamide gels. PMID- 6246825 TI - Changes of ejaculation due to suppression of noradrenaline biosynthesis by diethyldithiocarbamate. AB - The effects of diethyldithiocarbamate on manually induced erection and ejaculation and on monoamines in the brain and male reproductive organs were investigated in male mongrel dogs. From the results obtained in this study it was concluded that diethyldithiocarbamate suppresses ejaculation, although penile erection is maintained, and that the suppression is not mediated by the central nervous system but by the changes of the monoamine levels in the organs relating to sperm transport. PMID- 6246826 TI - [Effect of hyperbaric oxygenation on the succinate dehydrogenase and cytochrome oxidase activity of the visceral organs in intestinal obstruction]. PMID- 6246827 TI - [Virilizing luteoma during pregnancy: biochemical diagnosis and secretory profile of the tumor]. PMID- 6246828 TI - ["M" alpha-1-antitrypsin at term of pregnancy in an African population: concentration and microheterogeneity]. AB - For 19 multipars in Ivory Coast alpha-1-antitrypsin (A1AT) has been determined in mother's serum as well as in the cord serum and the amniotic fluid. In all cases the type of A1AT was MM. In 15 cases the pregnancies were normal and full term while four were premature (28th week). The A1AT levels obtained were found to be similar to the literature values and thereby do not seem to be influenced by the ethnic origin. Crossed electroimmunodiffusion analyses demonstrate a distribution of the different fractions of A1AT which is characteristic for each of the above groups of samples analysed. The similarity of the fractions in mother's serum and amniotic fluid indicate a maternal origin for A1AT of the latter. The cord blood shows a very characteristic increase in the peak M6. In the author's experience, they have only noticed such a peak in the blood of patients with primary liver cancer of the phenotype MM. PMID- 6246830 TI - Late pulmonary sequelae after type 7 adenovirus pneumonia. PMID- 6246829 TI - Nuclear diameters of breast cancer cells in tissue sections. AB - Nuclear diameters of breast cancer cells were measured on tissue sections in 100 cases. Processing the tissues for histology caused significant shrinkage and distortion of structures. Comparison between nuclear diameters measured on cytologic specimens and those measured on tissue sections must take into account a correction factor of 1.55 x. "Small nuclei only" were not found; in 19% of the tumors a "small nuclear type predominance" was evident. Twelve percent of the cases fell into the category of "more than 30% large nuclei" according to the cytologic criteria corrected for tissue sections. The importance of the correction factor is emphasized. PMID- 6246831 TI - [Hypoglycemia-inducing islet cell tumors. Measurement of blood glucose and insulin levels during operation. Results in seven cases (author's transl)]. PMID- 6246832 TI - A new method for the determination of plasma phenylalanine. AB - Two hundred microlitres of plasma is deproteinised, and chloride is removed with TCA/silver iodate. After centrifugation of the phenylalanine in the protein-free extract is oxidised to benzaldehyde with buffered sodium metaperiodate. The benzaldehyde is extracted into iso-octane, and the absorbance of the organic layer is measured at 240 nm. The method gives good agreement with a paper chromatographic method at normal and elevated levels of phenylalanine. All the reagents are stable indefinitely, and a single determination can be completed in 15 minutes. PMID- 6246833 TI - A simple direct solid-phase enzymeimmunoassay for cortisol in plasma. AB - A simple, direct solid-phase enzyme-labelled immunoassay for plasma cortisol was established using horseradish peroxidase/cortisol 21-hemisuccinate conjugate as "enzyme label. The antiserum, raised against a cortisol 21-hemisuccinate/bovine serum albumin conjugate, was coupled to cellulose to facilitate separation of free and bound steroid. Solvent extraction was avoided by the use of heat denaturation of the cortisol-binding globulin. This assay had a lower limit of sensitivity of 16.6 nmol/l and satisfied the standard criteria of accuracy and precision. Cortisol concentrations determined by enzymeimmunoassay were in excellent agreement with a gas liquid chromatography/mass spectrometry procedure (r=0.98, n=19) and also with the radioimmunoassay in current use (r=0.95, n=20). Cortisol levels after ACTH stimulatin and dexamethasone suppression in various subjects are presented. This enzymeimmunoassay is particularly applicable to the routine determination of plasma cortisol in small clinical laboratories or in those with a fluctuating workload. PMID- 6246835 TI - Peripheral nerve conduction in Fabry disease. AB - Peripheral nerve conduction was studied in 34 members, aged 3 to 54 years, from three separate kindreds with Fabry disease. Nerve conduction velocity was prolonged in one-third (11 of 34) of the study group. Of the 9 control family members with normal plasma alpha-galactosidase levels, 8 had normal velocity. A 6 year-old girl with normal plasma and leukocyte alpha-galactosidase levels and absent corneal deposits had slightly lower than normal nerve conduction velocity. One of the 3 obligate female carriers and 1 of 10 suspected carriers of Fabry disease had prolonged conduction velocity but normal distal latency. On the other hand, 8 of 12 males affected with Fabry disease demonstrated slow nerve conduction velocity while 4 of the 8 had prolonged distal latency. Frequently, only one of the two nerves studied showed abnormalities. These abnormalities were not related to patient age. Interfamilial variations in the abnormalities were present. PMID- 6246834 TI - Chronic Leigh Disease: a genetic and biochemical study. AB - The large family of a 21-year-old man who died of Leigh disease was investigated for evidence of neurological abnormalities and presence of the adenosine triphosphate-thiamine diphosphate phosphoryltransferase inhibitor factor. Of 217 persons (seven generations) included in the pedigree, 68 were examined neurologically and biochemically. Fourteen (20%), 5 of whom had abnormal neurological findings, were found to excrete the inhibitor factor. Clinical manifestations varied from severe neurological affliction to subtle deficits. A chronic relapsing course was frequently encountered, with exacerbations occurring in association with apparent metabolic stress. Parental consanguinity was identified in the propositus as well as in other family members with neurological abnormalities. Males and females were affected, and no vertical transmission of the trait was found. These multigenerational data suggest that Leigh disease in adults is inherited in an autosomal recessive manner and has variable degrees of expression with a wide spectrum of neurological manifestations. PMID- 6246836 TI - The acute sensory neuronopathy syndrome: a distinct clinical entity. AB - Four to twelve days following initial antibiotic treatment for a febrile illness, three adults suddenly experienced numbness and pain over the face and entire body. Each had received a penicillin or a semisynthetic derivative, and two patients also received other antibiotics. Signs appeared rapidly and included profound sensory ataxia, areflexia, and widespread sensory loss, primarily of large fiber modalities (proprioceptive sensibility). Slowed or absent sensory conduction was found. There was no weakness, and electrical study of muscle and motor nerve conduction was normal in all. The cerebrospinal fluid was acellular, and protein levels were elevated to 126 and 175 mg/dl in two cases and were normal in the other. Presently, all have a severe, static, residual sensory deficit. During follow-up of five years, no evidence of neoplastic disease or immunological disorder has appeared. Because of the rapid onset, widespread and pure sensory involvement, and poor recovery, the lesion is most likely confined to the dorsal root and gasserian ganglia (sensory neuronopathy). This pattern resembles that of the experimental lesions induced by doxorubicin and pyridoxine. It appears likely that either the previously administered antibiotics or the illness for which they were administered were of pathogenetic importance. We designate this previously unrecognized disorder the acute sensory neuronopathy syndrome and suggest that it represents a distinct, readily identifiable clinical entity. PMID- 6246837 TI - Diagnosis of infantile neuroaxonal dystrophy by skin biopsy. AB - Skin biopsy with ultrastructural examination of cutaneous nerves showed dystrophic axons (spheroids), confirming a diagnosis of infantile neuroaxonal dystrophy. Independent of axonal changes, a few endoneurial and Schwann cells showed cytoplasmic inclusion bodies composed of structures similar to those seen in the spheroids. PMID- 6246839 TI - Method for recovering viruses from river water solids. AB - Small numbers of virions (poliovirus 1) that had been adsorbed to river water solids were eluted by mixing the solids for 30 min with a 10% solution of beef extract that contained sufficient Na2HPO4 to bring the molarity of the salt to 0.05 and sufficient citric acid to bring the pH to 7. The virions were recovered by inoculating the beef extract onto cell cultures. With this method, 39 to 63% of the poliovirions that had been adsorbed onto the river water solids were recovered. PMID- 6246838 TI - Influence of estuarine sediment on virus survival under field conditions. AB - The survival of poliovirus 1 (LSc) and echovirus 1 (Farouk) in estuarine water and sediment was studied in Galveston Bay, Texas. Viruses were suspended in estuarine water and sediment both in dialysis tubing and in chambers constructed with polycarbonate membrane walls. Virus inactivation rates in seawater were similar in both types of chambers. Virus adsorption to sediment greatly increased survival time. The time required to inactivate 99% (T-99) of poliovirus increased from 1.4 days in seawater alone to 6.0 days for virus adsorbed to sediment at a relatively nonpolluted site. At a more polluted site, poliovirus T-99 was increased from approximately 1 h to 4925 days by virus adsorption to sediment. This study demonstrates that under field conditions virus association with estuarine sediment acts to prolong its survival in the marine environment. PMID- 6246840 TI - Eruptive histiocytoma of childhood. AB - A 9-year-old girl had a widespread papular eruption that was histologically characterized by benign histiocytes that were acid phosphatase-positive, but that lacked Langerhans' granules ultrastructurally. New lesions had continued to develop since the patient was 3 months old, and individual lesions had resolved over a period of two to three months. The histopathologic, histochemical, and ultrastructural findings in this patient were similar to those previously described for eruptive histiocytomas in adults. Papular histiocytomas in childhood may be found in histiocytosis X, reticulohistiocytoma, xanthogranuloma, xanthoma disseminatum, or eruptive histiocytoma. These diseases may be differentiated on the basis of differing histiocytic populations and the clinical courses of the lesions in each disorder. PMID- 6246842 TI - Poliomyelitis-like illness associated with asthma. AB - A 10-year-old girl with a combination of paralytic disease, resembling poliomyelitis, and asthma is described. The girl developed neurological symptoms 5 days after a severe attack of asthma. No aetiology to the flaccid paralysis could be demonstrated although Coxsackie B5 virus was isolated from a stool. A similar poliomyelitis-like illness associated with asthma has previously been reported in 13 cases from Australia and the UK. PMID- 6246841 TI - Treatment of hypophosphataemic vitamin D-resistant rickets with massive doses of 1 alpha-hydroxy-vitamin D3 during childhood. AB - Plasma levels of 1,25 dihydroxy-vitamin D (1,25-(OH)2-D) were low in 3 children with hypophosphataemic vitamin D-resistant rickets (HVDRR) during childhood, but increased after very large doses (0.5 to 2 micrograms/kg per day) of 1 alpha hydroxy-vitamin D (1 alpha-OH-D3). This treatment has two advantages. Firstly, hypercalcaemia is easily controlled by reducing the dose of 1 alpha-OH-D3 because of its short half-life. Secondly, the administration of 1 alpha-OH-D3 to patients with HVDRR can enhance the tubular reabsorption of phosphate, and this seems desirable in treating HVDRR. PMID- 6246843 TI - Course of rotavirus gastroenteritis in a closed community. AB - There were 3 outbreaks of rotavirus gastroenteritis accompanied by milky-white stools in a closed community of 21 children in Japan during a 2-year period. Several different clinical courses were observed as a result of clinical, serological, and virological observations. PMID- 6246844 TI - Pulmonary metastases in childhood sarcoma. AB - A retrospective analysis of 56 patients less than 19 years old with pulmonary metastases from previously diagnosed sarcomas was performed. Thirty patients had primary osteogenic sarcoma. Eighteen of them underwent a total of 37 thoracotomies. Overall survival was 20%. Twelve patients were noted to have metastatic Wilms' tumor, and 5 of them underwent 7 thoracotomies. This group had a 25% overall survival. Six patients had pulmonary metastases from Ewing's sarcoma. Four of these required pulmonary resection. The overall survival in these patients was 50%. The remaining 8 patients had pulmonary resection for various soft tissue malignancies, with an overll survival of 50%. The results of this review indicate a role for aggressive pulmonary resection in patients in whom the primary tumor is controlled and there is no other evidence of metastatic disease. The frequency of bilaterality and multicentric implants in patients with osteogenic sarcoma and Wilms' tumor suggest the efficacy of a median sternotomy approach in these patients. PMID- 6246845 TI - Oxygen utilization by Lactobacillus plantarum. II. Superoxide and superoxide dismutation. AB - Cell-free extracts of Lactobacillus plantarum contain non-proteinaceous compounds which mimic superoxide dismutase activity. Using the test system in which O-2 is generated by xanthine oxidase, superoxide dismutase activity is found in cell free extracts, where proteins are removed by precipitation. This activity is strongly decreased after dialysis of cell-free extracts. Superoxide dismutase activity was also investigated by means of pulse radiolysis. Cell-free extracts of Escherichia coli were also investigated as a comparison, which were known to contain superoxide dismutase. With cell-free extracts of both L. plantarum and E. coli the decay of O-2 was markedly increased. However, the type of reaction of the O-2 decay was of first order in the presence of E. coli extracts due to superoxide dismutase(s), and of second order in the presence of L. plantarum extracts, indicating that O-2 elimination is not an enzymic reaction. Mn2+ phosphate(s) might be responsible for the observed elimination of O-2. The production of O-2 is not detectable during NADH-, lactate- or pyruvate oxidase reactions in L. plantarum extracts. PMID- 6246846 TI - Cultured skin fibroblasts in lipidoses. Enzymatic, histochemical, and ultrastructural relationship in Fabry's Tay-Sachs, and Sandhoff's diseases. AB - Enzymatic, histochemical, and ultrastructural studies were performed on cultured skin fibroblasts from patients with Fabry's disease, Tay-Sach's disease, and Sandhoff's disease and from their families (carriers). alpha-Galactosidase activity was deficient in the proband with Fabry's disease (lower in the homozygotes than in the heterozygote). Levels of hexosaminidase A in the patient with Tay-Sachs disease and hexosaminidase A and B in the patient with Sandhoff's disease were deficient and were lower in her mother than in the control subject. Lysosome-like structures were observed in cultured fibroblasts from the patients with each disease, as well as in the heterozygote with Fabry's disease and the carrier with Tay-Sach's disease. The amount of the accumulating arrays in the lysosome-like structures was related to low level of enzymatic activity. PMID- 6246847 TI - Anterior interosseous-nerve paralysis as a complication of supracondylar fractures of the humerus in children. A report of two cases. AB - Two cases of anterior interosseous nerve syndromes following supracondylar fractures of the humerus in children are reported. In both cases spontaneous recovery began at 8 weeks and was complete at 10 weeks. The syndrome is discussed and the literature reviewed. PMID- 6246848 TI - Peripheral neuropathy after cis-platinum (II) (DDP) therapy. AB - A 56-year-old man developed a malignant fibrous histiocytoma in the left antecubital space in THE LEFT ANTECUBITAL SPACE IN September 1974. He underwent local resection, local radiation therapy, and chemotherapy with Adriamycin and Levamisole with resolution of the disease. In January 1977, a recurrent mass developed in the left antecubital space and electrophysiologic studies revealed segmental demyelination of the left median nerve across the tumor site. In July 1977, a Cis-diamminedichloplatinum (II) (DDP) therapy was instituted and 5 months later the patient developed paresthesias in both hands and both feet. Repeat nerve conduction studies revealed abnormalities in all 4 extremities consistent with a mixed sensorimotor peripheral neuropathy. Serial studies at 2-month intervals during DDP therapy showed further deterioration in nerve conduction. Following completion of DDP therapy, the patient's symptoms improved and subsequent nerve conduction studies done over an 11-month period showed improvement in nerve conduction with values approaching normal. PMID- 6246849 TI - Insulinoma. Experience in surgical treatment. AB - Sixty cases of insulinoma were treated surgically. The possible causes for failure to find the tumor during exploratory surgery are discussed. Simple enucleation is preferred in most cases of single or a few insulinomas. A technique of enucleation with minimal chance of injury to adjacent pancreatic ducts and larger blood vessels can be used. When no tumor is found after thorough exploratory procedures, controlled staged resection of the pancreas under blood glucose monitoring is the procedure of choice. Postoperative complications are common but the late results are gratifying provided the operation is carried out early in the course of the disease. PMID- 6246850 TI - Value of needle biopsy in outpatient diagnosis of breast cancer. AB - Outpatient needle biopsy of suspected breast cancers has been performed on 151 patients. Of 135 who were ultimately diagnosed as having a malignant tumor, 107 were correctly diagnosed on the initial needle biopsy, a success rate of 79%. The procedure is well tolerated by most patients and enables family support during a very stressful period. Furthermore, outpatient histopathologic confirmation of cancer allows adequate preoperative investigation and more efficient use of operating theater time. PMID- 6246851 TI - Skin wound closure. The effect of various wound closure methods on susceptibility to infection. AB - A continuous subcuticular polyglycolic acid suture with buried knots protected by a paint-on plastic dressing is shown to be resistant to surface contamination with Staphylococcus aureus in mice and is suggested to be superior to percutaneous skin sutures in infectability and to a tape closure in security. PMID- 6246852 TI - Minor base sequence differences between the genomes of two strains of murine cytomegalovirus differing in virulence. AB - Two strains of murine cytomegalovirus (MCMV), differing in virulence towards mice, were compared for possible genetic differences. The two strains behaved identically in cell cultures, although the virulent strain gave higher yields of infectious virus in salivary glands. The viral DNAs displayed identical reassociation kinetics, but minor differences in their base sequences were revealed by restriction endonuclease profiles. The endonuclease profile of the "virulent" strain was conserved during serial high multiplicity infection in vitro. PMID- 6246854 TI - Comparative analysis of the virion polypeptides specified by herpes simplex virus type 2 strains. AB - This paper reports on the variability of structural polypeptides of 32 strains of Herpes simplex virus 2 (HSV-2) isolated from various locations in the United States and Italy. Most strains were passaged a limited number of times at low multiplicity outside the human host; a few strains were characterized by numerous passages at variable multiplicities in cell culture. The acrylamide gel electrophoresis of polypeptides from purified virions revealed very few differences. Considering these differences the HSV-2 strains analysed can be classified into 3 groups according to the variability of three polypeptides. The study of polypeptides in HSV-2 infected cells revealed more differences than those seen in the structural proteins. Comparisons of the structural proteins specified by HSV-2 and HSV-1 virions, revealed clear variant features of the electrophoretic profiles, especially when pH of main gel was 8.9. PMID- 6246853 TI - Influence of poliovirus infection on S-phase and mitosis of the host cell. AB - Hep-2 cells were synchronized by a double thymidine block and infected with poliovirus type I (Mahoney) in hourly intervals after release from the second thymidine block. The S-phase is not prevented by a poliovirus infection but, with cells infected 0-4 hours after release, an increase of its duration is found. With an infection 5 hours and later after release, the duration of the S-phase is not different from that of an uninfected, synchronized control culture. DNA synthesis itself is slower early in S-phase and gets inhibited up to 75 per cent late in S-phase. All cultures show the first signs of a CPE 3.5 hours p.i. and, in spite of CPE, the cells continue to synthesize DNA. In infected cells a slightly higher peak of mitotic cells compared to control cultures is found. The time point of the mitotic peak is dependant of the time of infection and seems no longer controlled by the cell cycle. The mitotic indices are similar for all cultures infected at different times after release. When the cells are infected early after release CPE appears before mitosis and prevents the cells from entering mitosis. Cells which are infected towards the end of the S-phase finish mitosis normally before they exhibit characteristics of CPE. Extent and kinetics of poliovirus RNA synthesis and yield of virus progeny are not altered by the cell cycle. PMID- 6246855 TI - The application of a single radial haemolysis technique to foot-and-mouth disease virus-antibody study. AB - Experiments are described for the evaluation of the single radial haemolysis (SRH) technique applied to FMD virus, using a method involving the coupling of either antigen or antibody to sheep erythrocytes. The antigen coupling method detected specific antibody but the technique was found to be impractical as it gave reproducible results only with purified virions. However, the antibody coupling technique gave clear zones of lysis using tissue culture harvest virus as well as purified virus, and was also shown to be type specific for detecting antigen. A comparison of the SRH test with the single radial immunodiffusion (SRID) and complement fixation (CF) tests indicated that the SRH was a more sensitive test for assaying FMD antigen than either the SRID or CF tests. Although the SRH and SRID test results correlated well, those obtained in the SRH and CF tests did not. The test was not found to be superior to the CF test in assessing the quality of antigen since, like the CF test, it reacted both with the immunizing 140S antigen and the non-immunogenic 12S protein subunits. PMID- 6246856 TI - Anti-viral effects of single-stranded polynucleotides against avirulent Semliki Forest virus infection of mice and avirulent infection of rats with encephalomyocarditis virus. AB - Single-stranded polynucleotide preparations, which neither induce detectable interferon nor affect immune responses, suppress development of antiviral antibodies in mice infected with an avirulent strain of SFV. On a weight basis the antiviral activity of a mixture of poly(I) and poly(ho5C)-copolymer is greater than that of tRNA and similar antiviral effects are observed against a related virulent strain of SFV. EMC virus causes and avirulent infection of rats and development of EMC virus antibodies (routinely determined by assaying the protective effect of rat serum against EMC virus infection of mice) is suppressed when the rats are treated with tRNA or the mixture of poly(I) and poly(ho5C) copolymer. This suppression of antibodies to EMC virus appears to reflect reduction of virus replication. Treatments of 6 mg/rat i.p. or i.v. 6 hours before infection confer essentially the same antiviral effect as 3 times these polynucleotide doses administered during 3 days immediately post infection. These results with avirulent infections indicate that the previously reported antiviral effects of the single-stranded polynucleotides are not simply due to modifications of the tissue pathology which leads to death in the case of virulent virus infections. PMID- 6246857 TI - Histological study of the progression of herpes simplex virus in mice. AB - The progress of an experimental infection with Herpesvirus hominis type 1 was studied in newborn mice inoculated into the foot pad of the hind leg. To trace the viral antigen, the unlabeled antibody enzyme PAP (peroxidase/antiperoxidase) method was employed. The virus antigen appeared first in the epidermal and connective tissue cells of the inoculation site, and then progressed along the sciatic nerve. This nerve was studied by electron microscopy and showed active multiplication within the Schwann cells, with the production of virions, some of which were found in the intercellular spaces. No intra-axonal particles were observed. The infection then spread to the spinal ganglia and to the spinal cord. In this progression, the pia mater appeared to play an important role. From the spinal cord, the infection spread to the encephalon. The present study supports a mixed route for the neural transport of herpes simplex virus: a) by cell-to-cell transmission (Schwann and connective tissue cells in the sciatic nerve; meningeal cells, neurons and glial cells in the CNS); b) by a passive motion of the virions along the intercellular spaces. The inoculated virus also gave rise to viremia with viral multiplication in several viscera. PMID- 6246858 TI - Cohelical arrangement of the DNA strand in the core of Marek's disease virus particles. AB - Electron microscopic studies on Marek's disease virus demonstrated that fibrils of 20 to 30 A were arranged in a cohelical configuration within an electronopaque band of about 100 A thickness in the core of immature particles. These fibrils were presumed to be the DNA double helix itself. This configuration may represent an arrangement of the herpesvirus DNA. PMID- 6246859 TI - [Viral and Mycoplasma-induced glomerulopathies in children]. AB - Morphological examinations of kidneys from 227 children who had suffered from various generalized acute viral respiratory infections and mycoplasmosis established in 79 cases pathology of renalglomeruli, namely viral and mycoplasmic glomerulopathies. In 52 cases they corresponded to various forms of glomerulonephritis. The detection of deposites of immunoglobulins, virus and mycoplasma antigens suggest the association of these changes with the above mentioned infections. Besides, 27 children showed peculiar lesions of the renal glomeruli, associated with the cytopathic effect of respiratory viruses and mycoplasma. PMID- 6246860 TI - [Cloacogenic cancer of the rectum]. AB - Three cases of cloacogenous and 35 cases of squamous-cell carcinoma of the distal part of the rectum and anus were studied and compared histochemically to reveal considerable differences in mucopolysaccharides contained by the tumours. Squamous-cell carcinomas were characterized by the presence of glycogen which was not detected in cloacogenous carcinomas. In squamous-cell carcinomas, glycosamine glycanes were represented by sulfo- and sialo-mucin, while cloacogenous carcinomas largely contained a non-sulfated mucosubstance. The evidence obtained allows one to distinguish, among anal carcinomas of the rectum, a group of cloacogenous carcinomas that arose from the transitional epithelium of the serrate line and that differ from squamous-cell carcinomas in specific metabolic processes. PMID- 6246861 TI - Plasmacytic conjunctivitis with crystalline inclusions. Immunohistochemical and ultrastructural studies. AB - A 17-year-old girl had bilateral papillary conjunctivitis. Histologically, the lesion showed mature plasmacytes, plasmacytoid cells, and large mononuclear cells that exhibited myriad intracytoplasmic crystals. Electron microscopic studies disclosed that the large mononuclear cells, which showed plasmacytic differentiation, contained numerous crystalline inclusions. The crystals were formed within the rough-surfaced endoplasmic reticulum and exhibited a regular periodicity (8 nm). Histochemical methods disclosed that the composition of the crystals was mainly protein (immunoglobulin crystals). Immunoperoxidase techniques for demonstration of immunoglobulins showed that the crystalline inclusions contained IgG. The results of immunohistochemical findings correlated with the results of immunoelectrophoresis of the patient's serum. PMID- 6246862 TI - Corneal crystalline deposits associated with dysproteinemia. Report of two cases and review of the literature. AB - Two patients had multiple, fine, polychromatic corneal crystals on ocular examination. Peripheral corneal biopsies and electron microscopic studies demonstrated that the crystals, which were located solely within the cytoplasm of keratocytes, exhibited an internal periodicity of 10 nm and developed within dilated cisternae of rough-surfaced endoplasmic reticulum. Histochemical studies of the corneal crystals confirmed their proteinaceous nature (immunoglobulin crystals). Serum protein analysis showed that both patients had a monoclonal gammopathy with an elevated IgG level and increased K light chains. The associated proteinopathy was unsuspected in both patients until the nature of the crystals was established. Both patients had a neoplastic process; one had a previous diagnosis of Hodgkin's disease, and multiple myeloma developed in the other on follow-up studies. Clinicians should be aware of the possibility of a malignant disorder in patients with corneal crystal-line deposits. PMID- 6246863 TI - Protection from experimental ocular herpetic keratitis by a heat-killed virus vaccine. AB - New Zealand white rabbits were given limbal inoculations of a heat-killed suspension of herpes simplex virus (HSV) in a lysate of human embryonic kidney cells. At intervals of four to 14 days, the animals were challenged by intrastromal inoculation with 10,000 plaque-forming units of viable HSV. Epithelial keratitis, disciform edema, and necrotizing keratitis with neovascularization of the cornea developed in control animals. Epithelial keratitis and corneal edema also developed in the immunized animals during the first week after virus challenge, but these symptoms rapidly resolved during the following weeks. The absence of iritis, neovascularization, and necrotizing keratitis in the corneas of the immunized animals was particularly striking. PMID- 6246864 TI - Viral antigens in the immune ring of Herpes simplex stromal keratitis. AB - Corneal tissue obtained during superficial keratectomy from a patient with herpesvirus disciform keratitis was studied by immunoelectron microscopy. Clinically, this cornea had a dense central infiltrate with a circumferential opaque ring histologically resembling the immune ring described by Wessely. Histologically, along the line of altered keratocytes and ground substance, an infiltration of inflammatory cells was found. Herpesvirus particles were seen by electron microscopy in the corneal stroma, but these virus particles had abnormal, noninfective forms such as empty capsids and incomplete virions. By immunoelectron microscopy with a peroxidase-labeled antiherpesvirus antibody reagent, herpes-virus antigens were localized inthe corneal keratocytes and in the corneal stroma. The major localization of the virus antigens was in association with the herpes virions and surrounding vacuoles in the keratocyte nucleus and in the corneal stroma in the area of degenerating keratocytes. These findings support the view of a hypersensitivity mechanism in the pathogenesis of herpes simplex virus disciform keratitis. PMID- 6246865 TI - Collagenase levels in a new model of experimental herpetic interstitial keratitis. AB - A reproducible model of severe herpetic interstitial keratitis was developed by injecting live herpes simplex virus type 2 intrastromally into the corneas of presensitized rabbits. Herpes-infected corneas showed significantly more stromal infiltration and vascularization, iritis, conjunctivitis, and epithelial disease than the control corneas injected with cell supernatant without virus. Levels of total collagenase detected in the culture media of the herpes-infected corneas were high and were similar to those observed previously in alkali-burned rabbit corneas. Unlike alkali-burned corneas, the herpes-infected corneas showed much more of the enzyme in the latent form during the first two days of culture. PMID- 6246866 TI - Maximal nerve excitability testing vs electroneuronography. AB - In an article published in 1977, Adour et al compared electroneuronography (neuromyography) with maximal nerve excitability testing (NET) and reached the conclusion that the prognostic value of the latter was more reliable in facial paralysis. Further analysis of the results of Adour et al leads, however, to the opposite conclusion and illustrates how one may avoid the pitfalls that exist in using electrical stimulation to evaluate facial nerve function. Certainly, electroneuronography (ENoG) is not a foolproof method and experience is needed in order to avoid errors in technique and to achieve reproducible results. The great advantage of ENoG vs maximal NET is the quantitative analysis of the number of degenerated fibers and the assessment of an accurate degeneration profile in Bell's palsy. PMID- 6246867 TI - Parapharyngeal neoplasm of mixed mesenchymal and neuroepithelial origin. AB - A 20-year-old man had a left parapharyngeal neoplasm that displayed features of sarcoma of the nerve sheath, meningioma with an osseous component, rhabdomyosarcoma, and ganglioneuroma. The diverse cellular population suggests a tumor origin from the ectomesenchymal remnants of the neural crest. The mesenchymal part of the crest would differentiate into a variety of mesenchymal neoplastic elements, and the neuroectodermal (neuroepithelial) portion into the ganglioneuroma. These various neoplastic constituents then would form a neoplasm of mixed mesenchymal and neuroepithelial origin, or an ectomesenchymoma. PMID- 6246868 TI - Malignant fibrous histiocytoma of the maxillary sinus. Case report and literature review. AB - A case of malignant fibrous histiocytoma of the maxillary sinus, which to our knowledge is the third such report, involved a patient who was seen initially with nasal obstruction, swelling of the face, and visual disturbances. Three months after partial excision of the tumor and radiotherapy and chemotherapy, the patient died of bone and liver metastases. These tumors usually manifest initially with symptoms directly referable to the involved sinus. If there is any evidence of metastatic disease, the prognosis appears to be poor. PMID- 6246869 TI - The pathophysiology of insulin receptors: a model for peptide hormone action. PMID- 6246870 TI - Sialic acids in bone demineralised in organic solvents. AB - The sialic acid content of bovine shin bone, demineralised by a new process in ethanol-trimetrylammonium EDTA, was measured and compared with that of the original whole bone. New variants of the direct Ehrlich procedure, as well as the periodate-thiobarbituric acid assay, were employed. About 75% of the sialic acid remains in the bone matrix from ethanolic demineralisation, and the PAS reaction is correspondingly much more intense, compared with matrix from aqueous EDTA demineralisation. PMID- 6246872 TI - Posttransfusion hepatitis: epidemiology, experimental studies and US perspective. PMID- 6246871 TI - Posttransfusion hepatitis: European perspective and prophylaxis. PMID- 6246873 TI - Specificity of P2 primary alkylsulphohydrolase induction in the detergent degrading bacterium Pseudomonas C12B. Effects of alkanesulphonates, alkyl sulphates and other related compounds. AB - Primary alkanesulphonates were shown to serve as non-metabolizable (gratuitous) inducers of the P2 primary alkylsulphohydrolase enzyme in resting cell suspensions of Pseudomonas C12B. The effects of increasing concentrations of inducer on the production of enzyme were complex and suggestive of a multiphasic phenomenon. However, it was possible to determine Kinducer constants (analogous to Km or Ki) for alkanesulphonates of chain length from C7 to c12. these decreased with increasing chain length in a manner characteristic of an homologous series. Primary alkyl sulphates also served as good inducers of alkylsulphohydrolase, but valid kinetic values could not be obtained because these esters are good substrates for the enzyme and are therefore appreciably hydrolysed during the induction period. Small amounts of enzyme were also produced when cyprinol sulphate, dodecyltriethoxy sulphate C12H23-[O-CH2-CH2]3-O SO3-Na+), Crag herbicide and some secondary alkyl sulphates were tested as inducers. PMID- 6246875 TI - Characterization of the intermediates in the reaction of mixed-valence state soluble cytochrome oxidase with oxygen at low temperatures by optical and electron-paramagnetic-resonance spectroscopy. AB - The reaction of soluble mixed-valence-state (a3+CuA 2+.CuB + A32+) cytochrome oxidase with O2 at low temperature was studied by optical and e.p.r. spectroscopy. The existence of three intermediates [Clore & Chance (1978) Biochem. J. 173, 799-8101] was confirmed. From the e.p.r data it is clear that cytochrome a and CuA remain in the low-spin ferric and cupric states respectively throughout the reaction. No e.p.r. signals attributable to cytochrome a3 or CuB were seen in the intermediates. The difference spectra (intermediates minus unliganded mixed-valence-state cytochrome oxidase) and absolute spectra of the three intermediates were obtained. The chemcal nature of the three intermediates is discussed in terms of their spectroscopic properties. A catalytic cycle for cytochrome oxidase is proposed. PMID- 6246874 TI - Characterization of the low-temperature intermediates of the reaction of fully reduced soluble cytochrome oxidase with oxygen by electron-paramagnetic-resonance and optical spectroscopy. AB - The reaction of fully reduced soluble bovine heart cytochrome oxidase with O2 at 173K was investigated by low-temperature optical and e.p.r. spectroscopy, and the kinetics of the reaction were analysed by non-linear optimization techniques. The only e.p.r. signals seen during the course of the reaction are those attributable to low-spin cytochrome a3+ and CuA2+. Quantitative analysis of e.p.r. signals shows that, at the end point of the reaction at 173K, nearly 100% of CuA is in the cupric state but only about 40% of cytochrome a is in the ferric low-spin state. The optical spectra recorded at this stage of the reaction show incomplete oxidation of haem and the absence of a 655 nm absorption band. The only reaction scheme that accounts for both the e.p.r. and optical data is a four-intermediate mechanism involving a branching pathway. The reaction is initiated when fully reduced cytochrome oxidase reacts with O2 to form intermediate I. This is then converted into either intermediate IIA or intermediate IIB. Of these, intermediate IIB is a stable end product at 173 K, but intermediate IIA is converted into intermediate III, which is the stable state at 173 K in this branch of the mechanism. The kinetic analysis of the e.p.r. data allows the unambiguous assignments of the valence states of cytochrome a and CuA in the intermediates. Intermediate I contains cytochrome a2+ and CuA+, intermediate IIA contains low-spin cytochroma a3+ and CuA+, intermediate IIB contains cytochrome a2+ and CuA2+, and intermediate III contains low-spin cytochrome a3+ and CuA2+. The electronic state of the O2-binding CuBa3 couple during the reoxidation of cytochrome oxidase is discussed in terms of an integrated structure containing CuB, cytochrome a3 and O2. PMID- 6246876 TI - Inhibition of beta-lactamase of Bacillus licheniformis 749/C by compound PS-5, a new beta-lactam antibiotic. AB - By use of a new computer-assisted u.v.-spectrophotometric assay method, the kinetic parameters of the reaction catalysed by Bacillus licheniformis 749/C beta lactamase were re-examined and the mode of inhibition of the enzyme by compound PS-5, a novel beta-lactam antibiotic, was studied with benzylpenicillin as substrate. (1) The fundamental assay conditions for the determination of Km and V were examined in detail with benzylpenicillin as substrate. In 0.1 M sodium/potassium phosphate buffer, pH 6.8, at 30 degrees C, initial substrate concentrations of benzylpenicillin above 0.7 mM were very likely to lead to substrate inhibition. The Km value of the enzyme for benzylpenicillin at initial concentrations from 1.96 to 0.07 mM was calculated to be 97-108 microM. (2) The Km values of the enzyme for 6-aminopenicillanic acid, ampicillin and cephaloridine were found to be 25, 154-161 and 144-161 microM respectively. (3) Compound PS-5 was virtually unattacked by Bacillus licheniformis 749/C beta lactamase. (4) The activity of the enzyme was diminished by compound PS-5, to extents depending on the duration of incubation and the concentration of the inhibitor. The rate of inactivation of the enzyme by compound PS-5 followed first order kinetics. (5) In an Appendix, a new computer-assisted u.v. spectrophotometric enzyme assay method, in which a single reaction progress curve of time-absorbance was analysed by the integrated Michaelis-Menten equation, was devised for the accurate and precise determination of the kinetic constants of beta-lactamase. For conversion of absorbance readings into molar substrate concentrations, the initial or final absorbance reading that was independent of the reaction time was used as the basis of calculation. In calculation of Km and V three systematic methods of data combination were employed for finer analysis of the reaction progress curve. A list of the computer program named YF6TAIM is obtainable from the author on request or as Supplementary Publication SUP 50100 (12 pages) from the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., on the terms indicated in Biochem. J. (1978) 169, 5. PMID- 6246878 TI - Electrophoretically distinct forms of uridine kinase in the rat. Tissue distribution and age-dependence. AB - By the use of polyacrylamide-gel electrophoresis, uridine kinase from foetal rat liver was separated into four types designated I, II, III and IV in decreasing order of mobility towards the anode. The most anodic (type I) was found only in rapidly growing tissues, such as foetal liver and brain, postnatal spleen and tumour cells. In adult tissues, types II, III and IV were found in the kidney, and types III and IV in the spleen and the liver, whereas type IV was the sole form of uridine kinase present in the brain. PMID- 6246877 TI - Purification and properties of the P2 primary alkylsulphohydrolase of the detergent-degrading bacterium pseudomonas C12B. AB - The P2 primary alkylsulphohydrolase of the soil bacterium Pseudomonas C12B was purified to homogeneity (200-250-fold) by column chromatography on DEAE cellulose, Sephadex G-100 and butyl-agarose. The intact protein is a dimer with a mol. wt. of 160 000. Activity towards primary alkyl sulphate esters was maximal at pH 8.3, varied little in the range pH 7.8-8.7, but decreased sharply at higher pH. For a homologous series of primary alkyl sulphate substrates (C6-C12), logKm decreased linearly with increasing chain length, corresponding to a contribution to the free energy of association between enzyme and substrate of -2.5kJ/mol for each additional CH2 group in the alkyl chain. logKi for the competitive inhibition by secondary alkyl 2-sulphate esters followed a similar pattern ( 2.4kJ/mol for each additional CH2 group) except that only n-1 carbon atoms effectively participate in hydrophobic bonding, implying that the C-1 methyl group is not involved. logKi values for inhibition primary alkanesulphonates also depended linearly on chain length but with a diminished gradient, indicating a free-energy increment of -1.2kJ/mol per additional CH2 group. The collective results showed the presence of a hydrophobic site on the enzyme capable of accomodating an alkyl chain of considerable length. Cationic structures (in the form of arginine, lysine or histidine), whose presence might be expected for binding the anionic sulphate group, were not detectable at the active site. PMID- 6246879 TI - Chemical modification of the haem propionate of cytochrome c. AB - The significance of the exposed haem edge in cytochrome c was directly probed by chemically modifying the partially exposed haem propionate in the crevice region around residues threonine-78 and threonine-49. Reaction of tuna heart cytochrome c with a water-soluble carbodi-imide at pH 3.7 in the absence of any added nucleophilic base leads to the covalent addition of substituted N-acylureas to the protein at two sites. One site has been shown to be a haem propionate by isotope-tracer and i.r.-spectral analysis of haem purified from the apoprotein. The other site is aspartial acid-62 on the back of the molecule. The modified cytochrome c demonstrates abnormal properties, including auto-oxidizability, a reduction potential of + 105mV, a reversible transition to a high-spin species below pH 5.3, no 695 nm charge-transfer band in the ferric state and abnormal binding to mitochondrial membranes. The derivative does react with cytochrome oxidase in deoxycholate-treated submitochondrial particles or in purified preparations with a specific activity of 43-65% compared with that obtained with native cytochrome c. The results are consistent with the view that an intact haem crevice is essential for normal values for physiochemical characteristics, but the significant residual enzymic activity suggests that the electron-transfer interface and/or the cytochrome oxidase-binding site cannot be localized solely in the region of the exposed haem propionate. PMID- 6246880 TI - The isolation and characterization of a sequence-specific endonuclease from Anabaena subcylindrica. AB - An endonuclease, AsuI, was isolated from extracts of Anabaena subcylindrica on the basis of gel-electrophoretic analysis of digests of bacteriophage-lambda DNA with the paritally purified extracts. The enzyme requires Mg2+, but no other cofactors. Endonuclease AsuI recognizes the interrupted tetranucleotide sequence: (Formula: see tex), and breaks the phosphodiester bonds indicated by the arrows to leave single-stranded trinucleotide projections at the 5'-termini of the DNA fragments. PMID- 6246881 TI - The nucleotide sequences recognized by endonucleases AvaI and AvaII from Anabaena variabilis. AB - Determination of the 5'-terminal sequences flanking all the individual cleavage sites for endonuclease AvaI in bacteriophage-lambda DNA has shown that this enzyme recognizes the hexanucleotide sequences: (Formula: see text), This sequence is cut as shown by the arrows to give single-stranded 5'-tetranucleotide protrusions (cohesive ends). Endonucleases SmaI, XhoI and XmaI recognize different symmetrical subsets of this sequence and provide independent evidence for the occurrence of these subsets at particular endonuclease-AvaI cleavage sites in the bacteriophage-lambda genome. Further evidence for this structure came from the demonstration that DNA fragments generated by endonuclease AvaI can be ligated to form a discrete set of larger molecules and from nearest-neighbor analysis which showed that cytosine residues occurred at the 3'-side of cleavage points. The observation that endonuclease AvaII recognized a subset of the sites recognized by AsuI [Hughes, Bruce & Murray (1979) Biochem. J. 185, 59-63[ led to the deduction that AvaII recognize the pentanucleotide sequence: (Formula: see text), and breaks internucleotide bonds at the positions indicated by the arrows. PMID- 6246882 TI - Comparison of phosphorylation of ribosomal proteins from HeLa and Krebs II ascites-tumour cells by cyclic AMP-dependent and cyclic GMP-dependent protein kinases. AB - Phosphorylation of eukaryotic ribosomal proteins in vitro by essentially homogeneous preparations of cyclic AMP-dependent protein kinase catalytic subunit and cyclic GMP-dependent protein kinase was compared. Each protein kinase was added at a concentration of 30nM. Ribosomal proteins were identified by two dimensional gel electrophoresis. Almost identical results were obtained when ribosomal subunits from HeLa or ascites-tumour cells were used. About 50-60% of the total radioactive phosphate incorporated into small-subunit ribosomal proteins by either kinase was associated with protein S6. In 90 min between 0.7 and 1.0 mol of phosphate/mol of protein S6 was incorporated by the catalytic subunit of cyclic AMP-dependent protein kinase. Of the other proteins, S3 and S7 from the small subunit and proteins L6, L18, L19 and L35 from the large subunit were predominantly phosphorylated by the cyclic AMP-dependent enzyme. Between 0.1 and 0.2 mol of phosphate was incorporated/mol of these phosphorylated proteins. With the exception of protein S7, the same proteins were also major substrates for the cyclic GMP-dependent protein kinase. Time courses of the phosphorylation of individual proteins from the small and large ribosomal subunits in the presence of either protein kinase suggested four types of phosphorylation reactions: (1) proteins S2, S10 and L5 were preferably phosphorylated by the cyclic GMP-dependent protein kinase; (2) proteins S3 and L6 were phosphorylated at very similar rates by either kinase; (3) proteins S7 and L29 were almost exclusively phosphorylated by the cyclic AMP-dependent protein kinase; (4) protein S6 and most of the other proteins were phosphorylated about two or three times faster by the cyclic AMP-dependent than by the cyclic GMP-dependent enzyme. PMID- 6246883 TI - Steroidogenic action of calcium ions in isolated adrenocortical cells. AB - The corticotropin-induced increase of total intracellular and receptor-bound cyclic AMP in isolated rat adrenocortical cells was strictly dependent on extracellular Ca(2+). A rise in bound cyclic AMP with rising Ca(2+) concentrations was accompanied by a decrease in free cyclic AMP-receptor sites. A Ca(2+)-transport inhibitor abolished the rise in bound cyclic AMP induced by corticotropin. These data suggested that during stimulation by corticotropin some Ca(2+) has to be taken up in order to promote the rise of the relevant cyclic AMP pool. In agreement with this view, adenylate cyclase activity from isolated cells proved also to be dependent on a sub-millimolar Ca(2+) concentration in the presence of corticotropin and GTP. When cells were treated under specific conditions, corticosterone production could be activated by Ca(2+) in the absence of corticotropin (cells primed for Ca(2+)). Ca(2+)-induced steroidogenesis of these cells, in the absence of corticotropin, was also accompanied by an increase in total intracellular and receptor-bound cyclic AMP, as was found previously with corticotropin-induced steroidogenesis in non-primed cells. Calcium ionophores increasing the cell uptake of Ca(2+) were not able, however, to increase the cyclic AMP pools in non-primed cells, unlike corticotropin in nonprimed cells or Ca(2+) in cells primed for Ca(2+). It was concluded that during stimulation by either corticotropin or Ca(2+) a possible cellular uptake of Ca(2+) must be very limited and directed to a specific site which may affect the coupling of the hormone-receptor-adenylate cyclase complex. PMID- 6246884 TI - Phosphatidylcholine synthesis in the developing small intestine. AB - 1. Phosphatidylcholine synthesis in the foetal, newborn and adult small intestine of rats was studied by determination of cytidine diphosphocholine-1,2 diacylglycerocholine phosphotransferase (cholinephosphotransferase) and acyl-CoA 1-acyl-sn-glycerol-3-phosphocholine acyltransferase (lysophosphatidylcholine acyltransferase) activities and the incorporation of [1-14C]oleic acid into phosphatidylcholine. 2. Cholinephosphotransferase activity was low in foetal jejunum and ileum, increased 3-4 fold in the ileum by 6 days of age and by 12 days in the jejunum. Jejunal activity remained constant throughout weaning; ileal activity gradually decreased to values 25% of that of the jejunum. 3. Lysophosphatidylcholine acyltransferase activity was high in foetal jejunum and ileum, decreased 70% immediately after birth in the jejunum and increased to adult values by 12 days of age. Ileal activity decreased by 20% after birth, but decreased more rapidly at weaning to 30% of the activity in jejunum. 4. Initial rates and steady-state incorporation of [1-14C]oleic acid into phosphatidylcholine by jejunal rings of 10 day-old rats exceeded that observed in jejunal rings from adult rats by 2-4-fold. 5. In the postnatal jejunum, neither cholinephosphotransferase and lysophosphatidylcholine acyltransferase activities nor oleic acid incorporation were stimulated by cortisone administration in vivo. PMID- 6246885 TI - Differences in the metabolism of very-low-density lipoproteins by isolated beating-heart cells and the isolated perfused rat heart. Evidence for collagenase released extracellular lipoprotein lipase. AB - 1. The metabolism of VLD lipoproteins (very-low-density lipoproteins) was studied in intact isolated beating-heart cells and isolated perfused rat heart from starved animals by using [14C]triacylglycerol fatty acid-labelled VLD lipoprotein prepared from rats previously injected with [1-14C]palmitate. 2. 14C-labelled VLD lipoprotein was metabolized by the isolated perfused heart, but was only minimally metabolized by the heart cells unless an exogenous source of lipoprotein lipase was added. 3. Measurements of lipoprotein lipase at pH 7.4 with the natural substrate 14C-labelled VLD lipoprotein indicated that during collagenase perfusion of the heart the enzyme was released into the perfusate, the activity released being proportional to the concentration of collagenase used. Lipoprotein lipase activity in homogenates of hearts that had been perfused with collagenase showed a corresponding loss of activity. 4. At high perfusate concentrations of collagenase, inactivation of the released lipoprotein lipase occurred. 5. Lipoprotein lipase activity was largely undetectable in the homogenate of the isolated heart cells. 6. It is concluded that the lipoprotein lipase responsible for the hydrolysis of VLD lipoprotein triacylglycerol is predominantly located externally to the heart muscle cells and that its release can be facilitated by perfusion of the heart with bacterial collagenase. PMID- 6246886 TI - Calcium ion-stimulated phosphorylation of myelin proteins. AB - Myelin isolated from the central and peripheral nervous system contains a Mg2+ dependent protein kinase that catalyses phosphorylation of myelin-specific proteins. This phosphorylation is markedly stimulated by Ca2+ but not by cyclic AMP. Evidence was obtained that suggested an involvement of calmodulin-like protein in the stimulatory effects of Ca2+ on myelin phosphorylation. PMID- 6246887 TI - The metabolism of cyclic nucleotides in the guinea-pig pancreas. Cyclic AMP phosphodiesterase and cyclic GMP phosphodiesterase. AB - Both cyclic AMP phosphodiesterase and cyclic GMP phosphodiesterase were recovered mainly from the supernatant fractions of guinea-pig pancreas, but a higher proportion of the activity of the former was associated with the pellet fractions. The activities in the supernatant were not separated by gel filtration, but were clearly separated by subsequent chromatography on an anion exchange resin. The activities of cyclic AMP phosphodiesterase and cyclic GMP phosphodiesterase had high-affinity (K(m) 6.5+/-1.1mum and 31.9+/-3.9mum respectively) and low-affinity (K(m) 0.56+/-0.05mm and 0.32+/-0.03mm respectively) components. The activity of neither enzyme was affected by the pancreatic secretogens, cholecystokinin-pancreozymin, secretin and carbachol. Removal of ions by gel filtration resulted in a marked reduction in cyclic nucleotide phosphodiesterase activity, which could be restored by addition of Mg(2+). Mn(2+) (3mm) was as effective as Mg(2+) (3mm) in the case of cyclic AMP phosphodiesterase, but was less than half as effective in the case of cyclic GMP phosphodiesterase. The metal-ion chelators, EDTA and EGTA, also decreased activity. Ca(2+) (1mm) did not affect the activity of cyclic nucleotide phosphodiesterase when the concentration of Mg(2+) was 3mm. At concentrations of Mg(2+) between 0.1 and 1mm, 1mm-Ca(2+) was activatory, and at concentrations of Mg(2+) below 0.1mm, 1mm-Ca(2+) was inhibitory. These results are discussed in terms of the possible significance of cyclic nucleotide phosphodiesterase in the physiological control of cyclic nucleotide concentrations during stimulus secretion coupling. PMID- 6246888 TI - Subcellular localization of chicken kidney aryl acylamidase activity. AB - The intracellular localization of aryl acylamidase (aryl-acylamide amidohydrolase, EC 3.5.1.13) in chicken kidney was investigated. By separation on density gradients of the silica sol Ludox AM, the enzyme was localized in the mitochondrial fraction. This mitochondrial fraction was shown to be substantially free of lysosomal contamination. Subfractionation of the purified mitochondria indicates that the enzyme is located on the outer membrane, can be solubilized, and may be a suitable marker enzyme for kidney mitochondria. PMID- 6246889 TI - Metabolic control of potassium permeability in pancreatic islet cells. AB - The K(+) permeability of pancreatic islet cells was studied by monitoring the efflux of (86)Rb(+) (used as tracer for K(+)) from perifused rat islets and measuring the uptake of (42)K(+). Glucose markedly and reversibly decreased (86)Rb(+) efflux from islet cells and this effect was antagonized by inhibitors of the metabolic degradation of the sugar, i.e. mannoheptulose, iodoacetate, glucosamine and 2-deoxyglucose. Among glucose metabolites, glyceraldehyde reduced the K(+) permeability even more potently than did glucose itself; pyruvate and lactate alone exhibited only a small effect, but potentiated that of glucose. Other metabolized sugars, like mannose, glucosamine and N-acetylglucosamine, also decreased (86)Rb(+) efflux from islet cells. Fructose was effective only in the presence of glucose. Non-metabolized sugars like galactose, 2-deoxyglucose and 3 O-methylglucose had no effect. The changes in K(+) permeability by agents known to modify the concentrations of nicotinamide nucleotides, glutathione or ATP in islet cells were also studied. Increasing NAD(P)H concentrations in islet cells by pentobarbital rapidly and reversibly reduced (86)Rb(+) efflux; exogenous reduced glutathione produced a similar though weaker effect. By contrast, oxidizing nicotinamide nucleotides with phenazine methosulphate or Methylene Blue, or oxidizing glutathione by t-butyl hydroperoxide increased the K(+) permeability of islet cells. Uncoupling the oxidative phosphorylations with dicumarol also augmented (86)Rb(+) efflux markedly. In the absence of glucose, but not in its presence, methylxanthines reduced (86)Rb(+) efflux from the islets; such was not the case for cholera toxin or dibutyryl cyclic AMP. Glucose and glyceraldehyde had no effect on (42)K(+) uptake after a short incubation (10min), but augmented it after 60min; the effect of glucose was suppressed by mannoheptulose and not mimicked by 3-O-methylglucose. The results clearly establish the importance of the metabolic degradation of glucose and other substrates for the control of the K(+) permeability in pancreatic islet cells and support the concept that a decrease in the K(+) permeability represents a major step of the B-cell response to physiological stimulation. PMID- 6246890 TI - Effects of ACTH (corticotropin) analogues on steroidogenesis and cyclic AMP in rat adrenocortical cells. Evidence for two different steroidogenically responsive receptors. AB - Comparative studies on the mechanism of action of ACTH1-39 and ACTH5-24 [corticotropin-(1-39)- and corticotropin-(5-24)-peptides] on isolated rat adrenal cells were performed. The relationship between stimulated steroidogenesis and cyclic AMP was very different, suggesting that cyclic AMP does not play the same role in mediating the action of the two agonists. Data from three separate experiments showed that the competitive antagonist ACTH6-24 [corticotropin-(6-24) peptide] had mean inhibitor constants of 13.4 +/- 3.1 nM against ACTH1-39 and 3.4 +/- 1.0 nM against ACTH5-24, indicating that the steroidogenic actions of these two agonists are mediated by two different receptor types. We conclude that there are two possible mechanisms for corticotropin action, only one of which involves the necessary production of cyclic AMP. PMID- 6246892 TI - Effect of 2-n-heptyl-4-hydroxyquinoline N-oxide on proton permeability of the mitochondrial membrane. AB - The respiratory-chain inhibitor 2-n-heptyl-4-hydroxyquinoline N-oxide catalyses transmembrane proton transport driven by a pH gradient in isolated rat liver mitochondria. This effect explains the apparent blockade of net proton translocation by this compound in mitochondria respiring with ferrocyanide as described by Papa, Lorusso, Guerrieri, Boffoli, Izzo & Capuano [(1977) in Bioenergetics of Membranes (Packer, Papageorgiu & Trebst, eds.), pp. 377-388, Elsevier/North-Holland, Amsterdam] and by Lorusso, Capuano, Boffoli, Stefanelli & Papa [(1979) Biochem. J. 182, 133-147]. PMID- 6246891 TI - Capillaries of the adrenal cortex possess aminopeptidase A and angiotensin converting-enzyme activities. AB - The enzymes required to convert the prohormone angiotensin I into angiotensins II and III, secretagogues of aldosterone, are enriched in association with capillary endothelium isolated from rat adrenal cortex. Thus the secretion of aldosterone may be controlled, in part, by processing of peptides occurring within the adrenal gland itself. PMID- 6246893 TI - Cytochrome c degrading activity in rat liver mitochondria. PMID- 6246894 TI - 25-OHD3-26,23 lactone: demonstration of kidney-dependent synthesis in the pig and rat. PMID- 6246895 TI - Characterization of a new type of glycoprotein saccharides containing polysialosyl sequence. PMID- 6246896 TI - Affinity of ferredoxin for electrons from water and the regulation of cyclic photophosphorylation. PMID- 6246897 TI - Phosphoprotein associated with activation of the src gene product in myogenic cells. PMID- 6246898 TI - A specific, high affinity binding protein for 1 alpha,25-dihydroxy vitamin D in the chick oviduct shell gland. PMID- 6246899 TI - Resonance enhancement of the vibrations of cytochrome -a3 and its conformation in oxidized cytochrome oxidase. PMID- 6246900 TI - Alteration of cyclic nucleotide levels in phorbol 12-myristate 13-acetate treated myoblasts. PMID- 6246901 TI - A cytidine specific endonuclease activity associated with purified reovirus virions. PMID- 6246902 TI - Vitamin D-induced phosphate transport in intestinal brush border membrane vesicles. PMID- 6246903 TI - Enzyme activities related to 2,3-P2-glycerate metabolism in embryonic and fetal red cells. PMID- 6246904 TI - Elevated levels of collagenase and prostaglandin E2 from synovium associated with erosion of cartilage and bone in a patient with chronic Lyme arthritis. AB - A patient with chronic Lyme arthritis and roentgenographic evidence of bony erosion underwent a synovectomy; proliferative synovium (pannus), containing aggregates of small lymphocytes, was found adherent to eroded cartilage and bone. During 8 days in tissue culture, the synovial cells produced large amounts of collagenase and prostaglandin E2, but only low levels of both neutral and acid proteinases. Sixty-seven percent of the lymphocytes from the synovium were T cells; 19% were B cells. Attempts to identify agent/antigen in the synovial cells were unsuccessful. Thus, the synovium of this patient, whose disease appears to be tick-transmitted, resembles that of rheumatoid arthritis. This finding further supports the hypothesis that many possible agents, including infectious ones, trigger a common pathway in synovium, which leads to joint destruction. PMID- 6246905 TI - [Nephroblastoma with primary metastasis to the right thigh]. AB - A clinical case of Wilms' tumor with primary metastasis to right thigh without pulmonary metastasis that would explain the dissemination to soft tissues is presented. Considerations on the mechanism of metastasis dissemination are made in regard to the question in this particular location. We have not found a similar case in medical literature. PMID- 6246906 TI - Effect of anesthetics on membrane fluidity tested by two different techniques: EPR spin labels and polarization of perylene fluorescence. AB - We have investigated the effect of n-butanol on the spectroscopic properties of two types of probes, that are usually employed to detect membrane fluidity, in mitochondrial phospholipid vesicles and mitochondrial membranes. Although both a spin label (16-doxylstearate) and the fluorescent probe perylene detect a higher immobilization of the membrane in comparison with phospholipid vesicles, the effect of butanol in the case of the membrane is strikingly different with the two techniques employed, showing increased fluidity in the case of the spin label and decreased fluidity with the fluorescent probe. PMID- 6246907 TI - [Histopathological studies on Alzheimer glia type II in various liver diseases--a study of Best's carmine positive intranuclear inclusion (author's transl)]. PMID- 6246908 TI - Herpes zoster pericarditis. AB - A healthy 22-year-old man developed acute varicella pericarditis, characterised by an enanthem with diagnostic rising titres of varicella zoster antibodies but without the typical exanthem. This, the third reported case of varicella pericarditis, is the first to be documented without a typical varicella eruption. PMID- 6246909 TI - Effect of ketamine on transmission in sympathetic ganglia. AB - The effect of ketamine on sympathetic ganglion transmission has been studied using the guineapig isolated hypogastric nerve-vas deferens preparation. Ketamine produced a dose-dependent depression in the response to preganglionic stimulation (IC50 2.05 X 10--4 mol litre--1). No change in the response to postganglionic stimulation was recorded. The anti-cholinergic activity of ketamine was confirmed using the frog isolated rectus abdominis. PMID- 6246910 TI - Alcoholism aftercare and outcome: cross-lagged panel and path analyses. PMID- 6246911 TI - The evaluation of a new appetite-reducing agent (Prefil) in the management of obesity. PMID- 6246912 TI - Biochemical studies of the isolated rat glomerulus and the effects of puromycin aminonucleoside administration. AB - Using analytical subcellular fractionation techniques in combination with enzymic microanalysis, studies have been performed on the enzymology and organelle pathology of isolated glomeruli from normal rats and from animals with puromycin aminonucleoside nephrosis. There was a marked decrease in 5'-nucleotidase (plasma membrane) activity 2 days after puromycin aminonucleoside administration. In contrast, catalase (peroxisomes) and N-acetyl-beta-glucosaminidase (lysosomes) showed a significant rise during the first 6 days of treatment. By 10 days most marker enzymes showed a significant decrease in activity. The glomeruli were homogenized in isotonic sucrose and extracts were fractionated by isopycnic centrifugation on linear sucrose gradients in the Beaufay automatic small-volume zonal centrifuge. The properties of the principal organelles were characterized. ed. After 10 days of puromycin aminonucleoside treatment there were no marked differences in the centrifugal properties of these organelles. Morphological correlations with the biochemical changes are discussed and it is suggested that the plasma membrane changes represent the primary site of puromycin aminonucleoside damage. PMID- 6246914 TI - Impaired neutrophil function and myeloperoxidase deficiency in pregnancy. AB - The ability of neutrophils to phagocytose and kill Candida guilliermondii was investigated in 28 pregnant women and compared wtih 29 healthy controls. Phagocytosis was normal, but the ability to kill and digest Candida was reduced to 65% of normal. Quantitative myeloperoxidase measurement revealed a considerable reduction of this enzyme (55% of normal) while neutrophil alkaline phosphatase levels were nearly twice as high as in normals. It is suggested that both lack of myeloperoxidase and impaired candidacidal ability result from the discharge of the neutrophil's granules during previous phagocytosis of antibody antigen complexes in the circulation. PMID- 6246913 TI - Positive interaction between agonists in the aggregation response of human blood platelets: interation between ADP, adrenaline and vasopressin. AB - ADP, adrenaline and vasopressin interact positively as agonists in aggregating human blood platelets in vitro. This interaction is maximal if the addition of two of the agonists is separated by 10--20 s but decreases rapidly at longer intervals especially at low agonist concentrations. The agonist concentrations at which positive interaction gives full aggregation are significantly less than those required for such a response to each agonist alone. The lowest concentrations at which adrenaline and vasopressin interact positively are at least two orders of magnitude greater than the normal blood concentrations of these hormones, and at least an order of magnitude greater than the concentrations achieved in pathological states. Specifically antagonizing the adrenaline and ADP receptors showed that the response was to the second agonist added to the system. An inhibitor of intracellular Ca2+ movement (tetracaine) is equally effective in blocking the responses generated by a single agonist or by interaction of two agonists. Inhibitors which increase cyclic-3',5'-AMP concentration (adenosine, prostaglandin E1, dipyridamole) are more effective against the response to a single agonist than that to agonist interaction. These data suggest that positive agonist interaction results from effects on the concentrations of second messengers within the platelet rather than from a direct interaction on the membrane receptors or the transmembrane coupling mechanisms. PMID- 6246915 TI - Red cell pyrimidine 5'-nucleotidase and glutathione in myeloproliferative and lymphoproliferative disorders. AB - Red cell reduced glutatione (GSH) and pyrimidine 5'-nucleotidase (Pry 5'-NT) were measured in a variety of myeloproliferative and lymphoproliferative disorders. Raised levels of GSH were found in chronic lymphocytic leukaemia, Hodgkin's disease, non-Hodgkin's lymphoma, Waldenstrom's macroglobulinaemia and myeloma. Decreased activity of Pyr 5'-NT was found in acute myeloblastic leukaemia, acute lymphoblastic leukaemia, chronic granulocytic leukaemia, chronic lymphocytic leukaemia, Hodgkin's disease and non-Hodgkin's lymphoma. There was no correlation between the raised GSH levels and decrease Pry 5'-NT levels. PMID- 6246916 TI - Inclusions in red blood cells containing Hb S or Hb C. AB - To demonstrate and characterize red cell inclusions in 101 persons with Hb S or Hb C disorders three methods were used: (1) examination of unstained blood smears by dark field microscopy (DFM), (2) examination of blood smears after acid elution and staining (AE), and (3) measurement of membrane-associated denatured haemoglobin (MADH) in ghosts. The control group had inclusions in less than 5% of red cells by DFM and AE and the mean percentage of MADH per total cellular Hb was 0.030+/-0.016%. The highest percentages of red cells with inclusions and of MADH were present in clinically severe haemoglobin disorders, e.g. homozygous sickle cell disease (Hb SS) with less than 10% Hb F and Hb SOArab, with successively lower percentages in moderate to severe disorders, e.g. Hb SS-alpha thalassaemia, Hb-S-beta0 thalassaemia, Hb SC disease, and Hb SS with more than 10% Hb F, indicating agreement in results by three methods. In asymptomatic or mild disorders, e.g. Hb-S-beta+ thalassaemia, Hb CC, Hb AC and Hb AS, the results by AE and measurements of MADH were the same or similar to those in controls, while those by DFM were different. Of 56 patients with Hb SS or Hb SC, the group with functional asplenia had higher percentages of MADH and of red cells with inclusions than those with functioning spleens. Our study suggests that inclusions in sickling disorders may be due to denatured Hb S, with AE being the more accurate method for visualizing these inclusions, as results by this method correlate better with the amount of MADH than those by DFM. PMID- 6246917 TI - Isolation, subunit composition, and site of synthesis of human cytochrome c oxidase. AB - Cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1), the terminal oxidase of the respiratory chain in eucaryotic cells, has been purified from human placenta mitochondria. Seven polypeptides have been identified reproducibly by high-resolution electrophoresis of the enzyme complex through sodium dodecyl sulfate (Na-DodSO4)--urea polyacrylamide gels; these correspond closely in size to the subunits of beef heart cytochrome c oxidase. When HeLa cells, grown in suspension culture, were pulse-labeled with [35S]methionine in the presence of cycloheximide to inhibit cytoplasmic protein synthesis and chased with an excess of unlabeled methionine in the absence of the drug, the mitochondrially synthesized polypeptides were resolved into at least 17 components by NaDodSO4--urea polyacrylamide gel electrophoresis. After labeled HeLa mitochondria were mixed with human placenta mitochondria and the cytochrome c oxidase was isolated, three of the labeled components were found to copurify with the three largest subunits of the complex. We conclude that human cytochrome c oxidase contains seven subunits, the three largest of which are synthesized on mitochondrial ribosomes, while the other four are synthesized in the cytoplasm. PMID- 6246918 TI - Paramagnetic isoprenoid carrier lipids. 1. Chemical synthesis and incorporation into model membranes. AB - The synthesis, purification, and characterization of two types of spin-labeled glycosyl carrier lipids and shorter chain isoprenols are described. As models for phosphorylated lipids intermediates, phosphodiesters of tempol and the prenols dolichol, ficaprenol, solanesol, phytol, and farnesol were prepared. For analogues of neutral species each prenol was esterified with a pyrrolidinecarboxylic acid based label. Tripropylbenzenesulfonyl chloride was used as the condensing agent in both cases. Phosphodiester yields ranged from 36% for the 55-carbon compound to greater than 66% for the 95-carbon prenol. Both types of probes were incorporated into phospholipid bilayers, where each became oriented with the artificial head group at, or very close to, the water- hydrocarbon interface. Electron spin resonance spectra of the phosphodiesters are matrix dependent, indicating rapid isotropic tumbling in chloroform but highly anisotropic reorientation in unsaturated phosphatidylcholine (PC) hosts. Rotation or large amplitude oscillation about either or both the tempo C4--O linkage and the P--O (chain) bond as well as whole molecule rotation within the bilayer could account for the observed x-axis anisotropy. Segmental motion within the polyprene chain does not appear to be a determinant. PMID- 6246920 TI - Fluorescence photobleaching recovery measurements of surface lateral mobilities on normal and SV40-transformed mouse fibroblasts. AB - Lateral mobilities of fluorescent cell surface probes have been measured on normal (3T3) and transformed (SV3T3) cultured mouse fibroblasts. There is little discernible difference in the mobilities of a lipid analogue (diI), a fluorescent ganglioside derivative (GM1), and tetramethylrhodamine-labeled succinylated concanavalin A. The two cell lines showed expected differences in their abilities to grow in agar, to grow without serum, and to be agglutinated by lectins, indicating that changes of these properties in transformed cells are probably not mediated through increased overall membrane fluidity but are associated with distinct alterations in the mobilities of cell surface receptors. Both fluorescent dextran derivatives and antimouse cell surface antibodies were distinctly less mobile on SV3T3 cells, and the mobile fraction of Con A receptors was lower on SV3T3 cells. PMID- 6246919 TI - Paramagnetic isoprenoid carrier lipids. 2. Dispersion and dynamics in lipid membranes. AB - The transbilayer diffusion rates and self-association of spin-labeled glycosyl carrier lipids and other isoprenoids have been studied in model phospholipid membranes. Transposition rates of phosphorylated species in small (300 A) or large (greater than or equal to 1000 A) diameter unilamellar phosphatidylcholine (PC) vesicles are slow (t1/2 greater than 5 h at 25 degrees C); this argues against their proposed role in the transbilayer portage of sugar units during polysaccharide and glycoprotein assembly. The same probes mix well with several host lipids, remaining monomolecularly dispersed even at high ionic strength (0.5 M NaCl) or in the presence of various polyvalent cations. This behavior persists for several degrees beneath the transition temperature (Tc) of saturated lecithins. In contrast, neutral carboxylate analogues undergo pronounced reversible self-association. Aggregation is quite dependent on the probe concentration and nature of the host but only weakly temperature dependent above the Tc. Even at low probe concentrations (less than 0.5 mol %) in fluid membranes, aggregates persist above 75 degrees C. Unsaturation in the lecithin fatty acyl chains dramatically increases isoprenoid monomer solubility. Segregation appears to involve relocation of the entire molecule in the membrane interior. PMID- 6246921 TI - Purification and properties of chick renal mitochondrial ferredoxin. PMID- 6246922 TI - Renal mitochondrial ferredoxin active in 25-hydroxyvitamin D3 1 alpha hydroxylase. Characterization of the iron-sulfur cluster using interprotein cluster transfer and electron paramagnetic resonance spectroscopy. PMID- 6246923 TI - Cell-free synthesis of cartilage proteins: partial identification of proteoglycan core and link proteins. PMID- 6246925 TI - Covalent structure of collagen: amino acid sequence of alpha 1 (III)-CB5 from type III collagen of human liver. AB - Type III collagen was prepared from human liver by limited pepsin digestion, differential salt precipitation, and carboxymethylcellulose chromatography. Ten distinct peptides were obtained by cyanogen bromide digestion. The peptide alpha 1 (III)-CB5 was further purified by carboxymethylcellulose chromatography, and its amino acid sequence was determined. Automatic Edman degradation of intact alpha 1 (III)-CB5, tryptic and thermolytic peptides, and hydroxylamine-derived fragments was used to establish the total sequence. The mammalian collagenase site contained in the alpha 1 (III)-CB5 sequence was ascertained by digestion of native type III collagen with purified rheumatoid synovial collagenase. Collagenase cleavage occurred at a single Gly--Ile bond, one triplet before the corresponding specific cleavage site of type I collagen. The present work brings the known sequence of human liver type III collagen to include alpha 1 (III)-CB3 7-6-1-8-10-2-4-5. These correspond to the homologous region of alpha 1 (I)-CB0-1 2-4-5-8-3-7 residues 11--804. PMID- 6246924 TI - Reaction center--phospholipid complex in organic solvents: formation and properties. PMID- 6246926 TI - Fluorescent probe study of temperature-induced conformational changes in cytochrome oxidase in lecithin vesicle and solubilized systems. AB - A protein-bound label, N-(1-anilinonaphthyl-4)-maleimide (ANM), was used to investigate conformational changes in bovine heart cytochrome oxidase. The fluidity of cytochrome oxidase vesicles was monitored by a lipophilic probe, 1,6 diphenyl-1,3,5-hexatriene. The fluroescence intensity and emission anisotropy of these probes were examined between 4 and 60 degrees C in enzyme- dipalmitoyllecithin vesicles, in enzyme--dimyristoyllecithin vesicles, in enzyme- dioleoyllecithin vesicles, and in the soluble enzyme. The temperature-dependent changes in these quantities indicated that there were two types of conformational changes in oxidized cytochrome oxidase: one was attributed to an intrinsic enzyme conformation change which occurred around 20 degrees C, and the other was attributed to a conformational change induced by the lipid phase transition. Although ANM-reactive subunits of cytochrome oxidase in these four lecithin vesicle and solubilized systems were different from each other, subunit I always reacted with ANM in preference to other subunits. PMID- 6246927 TI - Specific binding and protection of form II SV40 deoxyribonucleic acid by ribonucleic acid polymerase II from wheat germ. PMID- 6246928 TI - Effect of adenosine 5'-triphosphate and adenosine 5'-diphosphate on the oxidation of cytochrome c by cytochrome c oxidase. AB - Adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate (ADP), and inorganic pyrophosphate partially inhibit the oxidation of exogenous cytochrome c by cytochrome c oxidase of submitochondrial particles (with or without detergent treatment) or by a purified preparation when it is assayed polarographically in buffers of nonbinding ions at pH 7.8. ATP is somewhat more inhibitory than ADP. The inhibition is never greater than 50%, and it is always less than an equal concentration of Mg2+ ions is present or when the assays are run at pH 6. In contrast, the effect of ATP, ADP, and pyrophosphate on oxidase assays run spectrophotometrically is a similar slight stimulation of the oxidase of submitochondrial particles treated with deoxycholate and little or no effect on purified oxidase. The reaction of the oxidase of submitochondrial particles with the endogenous cytochrome c is stimulated by the nucleotides, as is the reduced nicotinamide adenine dinucleotide (NADH) oxidase activity. The observations can be explained by binding of ATP, ADP, or pyrophosphate to cytochrome c so that the formation of an especially reactive combination of cytochrome c and cytochrome oxidase previously postulated [Smith, L., Davies, H. C., & Nava, M. E. (1979) Biochemistry 18, 3140] is prevented. The data give no evidence that respiration via cytochrome c oxidase is regulated physiologically by direct effects of ATP or ADP on its activity. PMID- 6246929 TI - Molecular motion in phospholipid bilayers in the gel phase: long axis rotation. PMID- 6246931 TI - Chromophore interactions in flavocytochrome c552: a resonance Raman investigation. AB - Resonance Raman spectra with both Soret and visible excitation have been obtained for Chromatium flavocytochrome c552 and its isolated diheme subunit under varying conditions of pH and inhibitor binding. The spectra are generally consistent with previously established classification schemes for porphyrin ring vibrations. The presence of covalently bound flavin in the protein was apparent in the fluorescent background it produced and in flavin-mediated photoeffects observed in heme Raman spectra obtained at high laser power. No flavin modes were present in the Raman spectra, nor was any evidence of direct heme-flavin interaction found by using this technique; however, a systematic perturbation of heme B1g vibrational frequencies was found in the oxidized holoprotein. The heme vibrational frequencies of c552 are compared to those of the diheme peptide and of other c-type cytochromes. They are consistent with an interpretation that involves pH-dependent changes in axial ligation and treats the hemes and flavin as isolated chromphores communicating via protein-mediated interactions. PMID- 6246930 TI - Binding of T4 endonuclease V to deoxyribonucleic acid irradiated with ultraviolet light. AB - Endonuclease V of bacteriophage T4 binds to UV-irradiated deoxyribonucleic acid (DNA) but not to unirradiated DNA. We have developed an assay to detect this binding, based on the retention of enzyme--DNA complexes on nitrocellulose filters. The amount of complex retained, ascertained by using radioactive DNA, is a measure of T4 endonuclease V activity. The assay is simple, rapid, and specific, which makes it useful for detecting T4 endonuclease V activity both in crude lysates and in purified preparations. We have used it to monitor enzyme activity during purification and to study binding of the enzyme to DNA under conditions that minimize the ability of the enzyme to nick DNA. From our data we conclude that (1) T4 endonuclease V binds to UV-irradiated DNA but not to DNA that has been previously incised by the endonuclease, (2) equilibrium between the free and complexed form of the enzyme is attained under our reaction conditions, (3) dissociation of enzyme--DNA complexes is retarded by sodium cyanide, and (4) retention of enzyme--DNA complexes on nitrocellulose filters is enhanced by high concentrations of saline--citrate. PMID- 6246932 TI - Deoxyribonucleic acid sequence organization in the genome of the dinoflagellate Crypthecodinium cohnii. AB - Details of the general DNA sequence organization in the dinoflagellate Crypthecodinium cohnii have been obtained by using hydroxylapatite binding experiments, S1 nuclease digestion .and electron microscopy of reassociated DNA. It has been found that roughly half of the genome is made up of unique sequences interspersed with repeated sequence elements with a period of approximately 600 nucleotides. This class represents roughly 95% of the total number of interspersed unique elements in the genome. The remaining 5% are uninterrupted by repeated sequences for at least 4000 nucleotide pairs. The interspersed repeated elements are narrowly distributed in length with 80% under 300 nucleotide pairs in length. About half of the repeated DNA (20-30% of the genome) is not interspersed among unique sequences. The close spacing of the short repeats interspersed throughout much of the genome is consistent with the occurrence of the huge network structures observed in the electron microscope for low Cot reassociation of moderately long fragments. An unusual class of heteroduplexes was detected in the electron microscope which is believed to derive from the reassociation of repeated sequences from different families which are frequently found adjacent to one another in different locations in the genome. The occurrence of this novel arrangement of repeated sequences may reflect the unusual organization of the dinoflagellate nucleus. However, in most respects the sequence arrangement in this unicellular alga is very typical of higher plants and animals. PMID- 6246933 TI - Evidence that deoxyribonucleic acid sequences flanking the ovalbumin gene are not transcribed. AB - The transcription of DNA sequences flanking the 5' end and 3' end of the ovalbumin gene was examined. First, various restriction endonuclease fragments corresponding to the 5' and 3' regions of the gene isolated and used as hybridization probes to assay for the presence of transcripts corresponding to these different regions in the chick oviduct nuclear RNA. Very little, if any, of the transcripts corresponding to sequences flanking the 5' and 3' structural sequences of the ovalbumin gene was detected in the steady-state nuclear RNA. Second, RNA was pulse labeled either in isolated nuclei or in an oviduct tissue suspension system and hybridized to DNA filters containing purified fragments of various 5'- and 3'-flanking regions. Our results again demonstrated that RNA was not synthesized from the 5'- and 3'-flanking regions surrounding the gene. Taken together, these results are consistent with the postulate that flanking DNA sequences are not transcribed and that the largest RNA species detected in the nuclear RNA are the initial transcripts. PMID- 6246934 TI - Reactivity of KB cell deoxyribonucleic acid polymerases alpha and beta with nicked and gapped deoxyribonucleic acid. PMID- 6246935 TI - High levels of a heat-labile calmodulin-binding protein (CaM-BP80) in bovine neostriatum. AB - Bovine brain contains a heat-labile, 80,000-dalton calmodulin-binding protein (CaM-BP80) which inhibits the calmodulin-dependent activities of cyclic 3',5' nucleotide phosphodiesterase, adenylate cyclase, and Ca2+-ATPase in vitro. CaM BP80 is composed of two polypeptides (60,000 and 18,500 daltons) present in a 1:1 ratio. An antibody directed against CaM-BP80 was raised in rabbits, and a radioimmunoassay was developed, having a sensitivity of 60 fmol of CaM-BP80. Using the radioimmunoassay, we determined the levels of CaM-BP80 in various bovine tissues. The protein was found primarily in the brain, present in particularly high levels in the neostriatum. These results, together with immunohistochemical localization of CaM-BP80 at the postsynaptic densities and the microtubules of postsynaptic dendrites [Wood, J.G., Wallace, R., Whitaker, J., & Cheung, W.Y. (1980) J. Cell Biol. 84, 66-76], suggest that the protein may have a role in the cerebrum at the site of neurotransmitter action and at the level of microtubular function. PMID- 6246936 TI - Photoaffinity labeling of the adenosine cyclic 3',5'-monophosphate receptor protein of Escherichia coli with 8-azidoadenosine 3',5'-monophosphate. AB - Photoaffinity labeling of the cAMP receptor protein (CRP) of Escherichia coli with 8-azidoadenosine 3',5'-monophosphate (8-N3cAMP) has been demonstrated. 8 N3cAMP is able to support the binding of (3H)d(I-C)n by CRP, indicating that it is a functional cAMP analogue. Following irradiation at 254 nm, (32P)-8-N3cAMP is photocross-linked to CRP. Photolabeling of CRP by (32P)-8-N3cAMP is inhibited by cAMP but not by 5'AMP. The data indicate that (32P)-8-N3cAMP is covalently incorporated following binding at the cAMP binding site of CRP. The (32P)-8 N3cAMP-CRP digested with chymotrypsin was analyzed by NaDodSO4-polyacrylamide gel electrophoresis. Of the incorporated label, one-third remains associated with the amino-proximal alpha core region of CRP [Eilen, E., Pampeno, C., & Krakow, J.S. (1978) Biochemistry 17, 2469] which contains the cAMP binding domain; the remaining two-thirds of the label associated with the beta region are digested. Limited proteolysis of the (32P)-8-N3cAMP-CRP by chymotrypsin in the presence of NaDodSO4 shows the radioactivity to be distributed between the molecular weight 9500 (amino-proximal) and 13,000 (carboxyl-proximal) fragments produced. These results suggest that a part of the carboxyl-proximal region is folded over and close enough to the cAMP binding site to be cross-linked by the photoactivated (32P)-8-N3cAMP bound at the cAMP binding site. PMID- 6246937 TI - Aldehyde-induced adenosine triphosphatase activities of fructose 6-phosphate and fructose kinases. AB - Chitose-6-P (2,5-anhydromannose-6-P) induces ATPase activity of fructose-6-P kinase with a Vmax 2-3% that of the normal kinase reaction with fructose-6-P or 2,5-anhydromannitol. Chitose (and presumably also chitose-6-P) is 52% hydrated in water while chitose deuterated at C-1 is 60% hydrated because of the equilibrium isotope effect of 0.73 on aldehyde hydration. Deuterated chitose-6-P gave a normal isotope effect on V/K of 1.23, but no effect on Vmax, showing that the free aldehyde is the activator and the hydrated form does not bind appreciably. With fructokinase, chitose can act either as a substrate, being phosphorylated at C-6 when adsorbed with C-6 next to MgATP, or as an inducer of ATPase activity when adsorbed with C-1 next to MgATP. The ATPase has a rate about 25% that of the kinase. PMID- 6246939 TI - Behavior of vesicular stomatitis virus glycoprotein in mouse LM cells with modified membrane-phospholipids. AB - LM cells in which the membrane phospholipids had been modified with choline analogues were infected with vesicular stomatitis virus. The choline analogues tested were choline, N,N'-dimethylethanolamine, N-monomethylethanolamine and ethanolamine. These modifications per se did not affect the syntheses of individual viral proteins. The viral glycoprotein was detected in the plasma membranes of all the modified cells by pronase digestion in pulse-chase experiments, but the amount of glycoprotein susceptible to proteolysis varied, decreasing in these modified cells in the following order: N,N' dimethylethanolamine- greater than choline- greater than N-monomethylethanolamine greater than ethanolamine-treated cells. After a 4-h chase, glycoprotein was mainly distributed in the plasma membranes of cells modified with N,N' dimethylethanolamine, whereas it was found in both the microsomes and plasma membranes of cells modified with other analogues. Fairly large amounts of glycoprotein were also found in the soluble fraction of ethanolamine-treated cells, but not in that of choline- or N,N'-dimethylethanolamine-treated cells. More precise experiments on the behaviour of glycoprotein with a short period of chase strongly suggested that migration of glycoprotein from the microsomes to the plasma membranes was fastest in cells modified with N,N'-dimethylethanolamine and slowest in cells modified with ethanolamine. Membrane lipid modifications also resulted in release of different numbers of progeny virions from the cells, release of virions from the cells decreasing in the following order: N,N' dimethylethanolamine- greater than choline- greather N-monomethylethanolamine- greater than ethanolamine-treated cells. These results indicate that modification of membrane phospholipids influences not only the insertion of glycoprotein into the microsomes and its migration to the plasma membranes, but also the production of progeny virions. PMID- 6246938 TI - Photosystem II oxidation of charged electron donors. Surface charge effects. AB - Reactions occurring on the oxidizing side of Photosystem II have been studied in Tris-washed chloroplasts by monitoring the decay kinetics of EPR signal IIf, arising from the photoinduced oxidation of Z, an intermediate in the electron transport chain between P-680 and the water-splitting enzyme. Upon addition of electron donors, signal IIf follows pseudo-first order decay kinetics with rates dependent on the chemical nature of the donor. Negatively charged donors (I-, Fe(CN)6(4-), W(CN)8(4-) are poor reducing agents for Z.+ whereas neutral donors (benzidine, hydroquinone, diphenylcarbazide) are more efficient, their effectiveness paralleling their lipophilicity. The slow signal IIf reduction observed with the charged donors is consistent with the non-polar nature of the thylakoid membrane and a location for Z toward the inner membrane surface. It most probably exists in a hydrophobic site as indicated by the positive correlation between rate constant and lipophilicity for the neutral donors. A detailed study of the mechanism of Photosystem II reduction by ascorbic acid has been carried out. The pH dependence of the decay kinetics of signal IIf in the presence of this donor is consistent with a model in which both the neutral acid and the ascorbate mono-anion serve as reducing agents to Z.+. The second-order rate constant for reduction by the mono-anion is less than that of the neutral acid and is found to vary with the suspension pH. This observation is interpreted to indicate the occurrence of negative charge on the inner membrane surface in the vicinity of Z. Additional experiments, which assessed the effect of mono- and divalent cations and of cationic detergents on the signal IIf reaction rate constants, support both the presence of negative surface charge and its location on the membrane inner surface. PMID- 6246940 TI - Relation between phosphorylation and adenosine triphosphate-dependent Ca2+ binding of swine and bovine erythrocyte membranes. AB - The correlation between the ATP-dependent Ca2+ binding and the phosphorylation of the membranes from swine and bovine erythrocytes was studied. The Ca2+ binding was measured by using 45CaCl2, and the phosphorylation by [gamma-32P]ATP was studied with the technique of SDS polyacrylamide gel electrophoresis. 200 mM NaCl and KCl markedly repressed the Ca2+ binding of swine erythrocyte membranes. The radioactivity of 32P-labelled membranes was revealed mainly in 250,000 dalton protein and a lipid fraction. NaCl and KCl also repressed the phosphorylation of the lipid which was identified as triphosphoinositide by paper chromatography. The membranes prepared from trypsin-digested erythrocytes completely retained the Ca2+-binding activity, and lost 30% of (Ca2+ + Mg2+)-ATPase activity. The Ca2+ binding and ATPase activity of isolated membranes decreased to 55% and to 0%, respectively, by tryptic digestion. Neither the Ca2+ binding nor the phosphorylation of polyphosphoinositides were detected in bovine erythrocyte membranes. These results suggest that the formation of triphosphoinositide rather than the (C2+ + Mg2+)-ATPase of membranes is linked to the ATP-dependent Ca2+ binding of erythrocyte membranes. PMID- 6246941 TI - Potential-dependent interaction of toxin from venom of the scorpion Buthus eupeus with sodium channels in myelinated fibre: voltage clamp experiments. AB - 1. The steady-state characteristics of the sodium channel gating in the nodal membrane were determined under voltage clamp conditions before and after treatment with toxins from the venom of scorpion, Buthus eupeus. 2. The apparent binding constant (KA) of the toxin was determined for different levels of the membrane potential. At potentials more negative than -120 mV, KA tends to a constant level. KA is maximum at about -80 mV, and it decreases as the potential is teduced to 0 mV. 3. A model assuming that the voltage dependency of KA is mainly due to the difference in electrical energy between inactivated states of normal and poisoned channels is proposed. An additional decrease in overall binding of toxin results from the transition of a fraction of the sodium channels into the state of slow inactivation. PMID- 6246942 TI - Initial membrane reaction in peptidoglycan synthesis: perturbation of lipid phospho-N-acetylmuramyl-pentapeptide translocase interactions by n-butanol. AB - Phospho-N-acetylmuramyl-pentapeptide translocase, the initial membrane enzyme in the biosynthesis of peptidoglycan, requires a lipid microenvironment for function. n-Butanol was reversibly intercalated into membranes to perturb the hydrophobic interactions in this microenvironment in order to define further the role of lipid. In the concentration range for maximal stimulation of enzymic activity (0.12-0.18 M), n-butanol causes a 40% decrease in the fluorescence emission of the dansylated product, undecaprenyl diphosphate-(N epsilon dansyl)pentapeptide. Since no change in emission maximum occurs below 22 degrees C in the presence of 0.12 M n-butanol, it is concluded that intercalation of this alkanol causes an increase in fluidity. Above 22 degrees C this concentration of n-butanol causes both a decrease in the fluorescence emission and a red shift in the emission maximum. It is concluded that a polarity change as well as fluidity change occurs above 22 degrees C. n-Butanol also causes a significant change in the phase transition experienced by the dansylated lipid product. Thus, it is possible with n-alkanols, e.g. n-butanol, to perturb lipid-translocase interactions resulting in an increase in fluidity in the microenvironment of the enzyme. This change in fluidity correlates with a stimulation of enzymic activity. PMID- 6246944 TI - Electrophysiological modifications induced by the fluorescent probe, pyrene, on Myxicola giant axons. AB - Current- and voltage-clamp experiments on Myxicola giant axons labelled with pyrene showed decreased Na+ and K+ conductances. The low-frequency membrane capacity and the gating charge transfer were slightly reduced. It may be inferred that pyrene is incorporated in some hydrophobic membrane domains close to the ionic channels. PMID- 6246943 TI - The redistribution of membrane surface immunoglobulin induces the rearrangement of some membrane integral proteins. AB - We investigated whether the redistribution of surface membrane receptors is associated with rearrangement of integral membrane proteins. Using a newly developed process, which combines histochemical analysis with an immunofluorescence or immuno-electron microscopy-staining technique, we studied the redistribution of two membrane-bound enzymes, 5'-nucleotidase and ATPase, on mouse splenic lymphocytes and B lymphoma cells induced by anti-mouse immunoglobulin antibodies. Labeling and capping of the membrane surface immunoglobulin induced a similar rearrangement of both 5'-nucleotidase and ATPase from uniform distribution at 4 degrees C into 'patches' and caps at 37 degrees C. PMID- 6246945 TI - Reconstitution of active acetylcholine receptor by hybridisation of binding site blocked with ion channel-blocked acetylcholine receptor protein. AB - The nicotinic acetylcholine receptor regulates the ion permeability of the postsynaptic membrane. This report presents evidence that the transmitter binding site and the ion channel may be located on distinct subunits. By hybridisation of receptor complexes, in which the transmitter binding site was blocked with complexes in which the ion channel was irreversibly inhibited, we reconstituted active acetylcholine receptor complexes. The reconstituted system was similar to the native receptor in its ability to regulate the ion permeability of lipid vesicles in response to nicotinic cholinergic effectors. PMID- 6246946 TI - Lipid-lipid and lipid-protein interactions in chromaffin granule membranes. A spin label ESR study. AB - The ESR spectra of six different positional isomers of a stearic acid and three of a phosphatidylcholine spin label have been studied as a function of temperature in chromaffin granule membranes from the bovine adrenal medulla, and in bilayers formed by aqueous dispersion of the extracted membrane lipids. Only minor differences were found between the spectra of the membranes and the extracted lipid, indicating that the major portion of the membrane lipid is organized in a bilayer arrangement which is relatively unperturbed by the presence of the membrane protein. The order parameter profile of the spin label lipid chain motion is less steep over the first half of the chain than over the section toward the terminal methyl end of the chain. This 'stiffening' effect is attributed to the high proportion of cholesterol in the membrane and becomes less marked as the temperature is raised. The isotropic hyperfine splitting factors of the various positional isomers display a profile of decreasing polarity as one penetrates further into the interior of the membrane. No marked differences are observed between the effective polarities in the intact membranes and in bilayers of the extracted membrane lipids. The previously observed temperature-induced structural change occurring in the membranes at approx. 35 degrees C was found also in the extracted lipid bilayers, showing this to be a result of lipid-lipid interactions and not lipid-protein interactions in the membrane. A steroid spin label indicated a second temperature-dependent structural change occurring in the lipid bilayers at lower temperatures. This correspond to the onset of a more rapid rotation about the long axis of the lipid molecules at a temperature of approx. 10 degrees C. The lipid bilayer regions probed by the spin labels used in this study may be involved in the fusion of the chromaffin granule membrane leading to hormone release by exocytosis. PMID- 6246947 TI - Transferrin-binding and iron-binding proteins of rabbit reticulocyte plasma membranes. Three distinct moieties. AB - 1. Transferrin-membrane complexes and iron-binding membrane complexes were solubilized with sodium dodecyl sulfate from the plasma membranes of reticulocytes that had been incubated with (59Fe,125I)-labeled transferrin. Gel filtration of solubilized material demonstrated 125I-labeled transferrin complexed to two moieties, a minor component (Peak I) of apparent molecular weight 435,000 and a major component (Peak II) of apparent molecular weight 200,000. Most of the membrane 59Fe was located in Peak I. 2. Sepharose-bound anti transferrin was used to purify the 125I-labeled transferrin-membrane complexes. The 59Fe/125I ratio in the transferrin complex purified from Peak I was the same as in the original transferrin and thus contained membrane-bound transferrin to which the 59Fe was still attached. The 59Fe/125I ratio in the purified Peak II transferrin complex was 0.33 times that of the original transferrin, indicating that more than 60% of its 59Fe had been delivered to the reticulocyte. 3. The purified transferrin complexes analyzed by SDS-polyacrylamide gel electrophoresis demonstrated a single band of apparent molecular weight 78,000 both by Coomassie blue stain for protein and by 125I radioactivity. The specific activity of this material was 0.27 and 0.56 times that of the original transferrin for Peak I and Peak II, respectively, indicating that transferrin in Peak I and II was bound to a membrane component with a molecular weight similar to that of transferrin. 4. The isoelectric focusing pattern of the Peak II transferrin complex showed isoelectric points of pH 6.7 and 6.2 compared to pH 5.4 for transferrin. 5. On the basis of these studies we propose that transferrin is first bound to a membrane protein and then delivers iron to a membrane component distinct and separate from the transferrin-binding moiety. Prior to its release, transferrin markedly depleted of iron is still bound to a component in the plasma membrane. PMID- 6246948 TI - Production and characterization of antibody blocking epidermal growth factor:receptor interactions. AB - Membranes were prepared from the human epithelioid carcinoma cell line A-431 which has approx. 2 . 10(6) epidermal growth factor receptors per cell. This membrane preparation which retained a high epidermal growth factor binding specific activity was used as an antigen to produce antisera in rabbits. Double immunodiffusion experiments demonstrated that the immune serum contained precipitating antibodies to several components of detergent solubilized A-431 membranes. The immunoglobulin G fraction of this immune sera inhibited 125I labeled epidermal growth factor binding to receptors in: (1) intact human and mouse cells; (2) membrane preparations from A-431 cells and human placenta, and (3) solubilized A-431 membranes. Inhibition of 125I-labeled epidermal growth factor binding was observed with divalent and monovalent fragments of immunoglobulin G prepared from the immunoglobulin G fraction. Also, the immunoglobulin G fraction blocked growth factor binding to membranes at low temperature (5 degrees C). Anti-A-431 antibody blocked the induction of DNA synthesis in quiescent fibroblasts by epidermal growth factor in a manner similar to that of anti-epidermal growth factor antibody. Addition of either anti-A431 or anti-epidermal growth factor antibodies to fibroblasts at times up to 5 h after the addition of epidermal growth factor completely reversed the hormone's mitogenic potential. At later times (after 12 h) addition of either antibody was without effect on the stimulation of DNA synthesis by epidermal growth factor. Anti-A-431 antibody did not block the induction of DNA synthesis in fibroblasts by fibroblast growth factor or serum. PMID- 6246949 TI - Effects of ouabain and isoproterenol on potassium influx in the turkey erythrocyte. Quantitative relation to ligand binding and cyclic AMP generation. AB - Studies have been carried out in the turkey erythrocyte to examine: (1) the influence of external K+ concentration on both [3H]ouabain binding and the sensitivity of potassium influx to inhibition by ouabain and (2) the quantitative relation between beta-adrenergic receptor site occupancy, agonist-directed cyclic AMP generation and potassium influx rate. Both [3H]ouabain binding and the ability of ouabain to inhibit potassium influx are markedly reduced at increasing external K+ concentrations, and at each K+ concentration the concentrations of ouabain required for half-maximal binding to the erythrocyte membrane and for half-maximal inhibition of potassium influx are identical. Both basal and isoproterenol-stimulated potassium influx rise with increasing external K+ concentrations. In contrast to basal potassium influx, which is 50-70% inhibitable by ouabain, the isoproterenol-stimulated component of potassium influx is entirely insensitive to ouabain. At all concentrations of K+, inhibition of basal potassium influx by ouabain is linear with ouabain binding, indicating that the rate of transport per unoccupied ouabain binding site is unaffected by simultaneous occupancy of other sites by ouabain. Similarly, the rate of isoproterenol-stimulated cyclic AMP synthesis is directly proportional to beta-adrenergic receptor occupany over the entire concentration-response relationship for isoproterenol, showing that at all levels of occupancy beta adrenergic receptor sites function independently of each other. Analysis of the relation of catecholamine-dependent potassium transport to the number of beta adrenergic receptor sites occupied indicates an extremely sensitive physiological system, in which 50%-maximal stimulation of potassium transport is achieved at less than 3% receptor occupancy, corresponding to fewer than ten occupied receptors per cell. PMID- 6246950 TI - Adenosine transport by a variant of C1300 murine neuroblastoma cells deficient in adenosine kinase. AB - The uptake of adenosine by an adenosine kinase deficient variant of C1300 murine neuroblastoma cells has been studied in the absence and in the presence of erythro-9-(2-hydroxy-3-nonyl)adenine, a potent adenine deaminase inhibitor. Although 100 micro M inhibitor completely blocks the metabolism of adenosine under the conditions studied, the uptake of adenosine is concentrative, i.e., the intracellular adenosine concentration exceeds the extracellular concentration. This concentrative effect decreases as the concentration of adenosine increases and is hypothesized to be due to the binding of adenosine to an intracellular component. Despite this concentrative effect, we believe that the kinetics of uptake, as determined in experiments with short (10-20 s) uptake periods, reflect the kinetics of adenosine transport by a facilitated diffusion process. This nucleoside transport system appears to be nonspecific in that the transport of adenosine is competitively antagonized by thymidine. It does not appear to be necessary to inhibit adenosine deaminase in order to study transport in these cells as the Km for transport is not affected by the presence of erythro-9-(2 hydroxy-3-nonyl)adenine. However, erythro-9-(2-hydroxy-3-nonyl)adenine does depress the V for transport. This effect of the inhibitor is probably not due to the inhibition of adenosine deaminase as the transport of thymidine is similarly affected. PMID- 6246951 TI - Stimulation of muscle glycogen synthase phosphatase by polyamines. AB - The naturally-occurring polyamines were found to stimulate glycogen synthase phosphatase from rat skeletal muscles. The sequence of effectiveness in the stimulation was spermine greater than spermidine greater than putrescine. It was shown that the spermine-sensitive phosphatase was present primarily in the soluble fraction of the muscle extract. In the presence of spermine, the phosphatase activity can be further stimulated by Mn2+; however, a lower Mn2+ concentration is required for the activation of the enzyme in comparison with that in the absence of spermine. Kinetic studies indicated that activation of glycogen synthase phosphatase by spermine was achieved by an increase in its V without significant alteration in the Km, suggesting that spermine directly stimulated the catalytic efficiencly of the phosphatase enzyme. PMID- 6246952 TI - Cyclic nucleotide phosphodiesterase activities from pig coronary arteries. Lack of interconvertibility of major forms. AB - DEAE-cellulose chromatography, with or without dithiothreitol and over a pH range of 6.0 to 8.5, resolved two phosphodiesterase activities (peaks I and II) from the soluble fraction of pig coronary arteries. The activity of peak I was increased by calmodulin (3-7-fold), whereas that of peak II was not. Chromatography of peak I on Biol-Gel A-0.5 m columns resolved two peaks of phosphodiesterase activity (peaks Ia and Ib). Peak Ia was eluted in the presence or absence of 0.1 M KCl and was relatively insensitive to calmodulin. Peak Ib was eluted only in the presence of KCl and was sensitive to calmodulin. The substrate specificity and kinetic behavior were the same for peaks I, Ia, and Ib. Repeated gel chromatography of either peak Ia or Ib, under appropriate conditions, yielded a mixture of peaks Ia and Ib. Peak Ia appears to be a reversible aggregate of peak Ib. Gel chromatography of peak II resolved only one phosphodiesterase activity, which was eluted without KCl, was highly specific for cyclic AMP, was not sensitive to calmodulin and migrated differently on the gel column than either peak Ia or Ib. Sucrose density gradient centrifugation of the soluble fraction from pig coronary arteries in the presence or absence of dithiothreitol resolved two peaks of phosphodiesterase activity (6.6 S and 3.6 S) which were similar to peaks I and II separated by DEAE-cellulose chromatography with regard to their substrate specificity and their sensitivity to calmodulin. Upon recentrifugation, each of the two peaks of phosphodiesterase activity gave a single peak of activity which migrated with the same S value as did its parent. These results indicate that the two major forms of phosphodiesterase of pig coronary arteries, which are representative of those found in many tissues, are not interconvertible in cell-free systems. PMID- 6246953 TI - Activation of human leukocyte collagenase by compounds reacting with sulfhydryl groups. PMID- 6246954 TI - Diaphorase P: a new fetal isozyme identified in human placenta. AB - Human placenta contains a thermostable, cytosolic NADH-diaphorase which is different from the other diaphorases and which we designate as diaphorase P. It is specific for NADH and reduces artificial substrates such as dichlorophenol and tetrazolium derivatives, but not natural substrates such as methemoglobin, cytochrome b5 or lipoate. It is antigenically distinct from the ubiquitous red cell type NADH-diaphorase (soluble cytochrome b5 reductase) specified by the DIA1 locus. Using electrophoretic and immunologic methods, it was possible to detect diaphorase P in various fetal tissues (brain, liver, kidney, muscle), whereas was not found in adult tissues with the exception of the brain. This enzyme, the physiological role of which remains unknown, appears to belong, therefore, to the category of fetal proteins. Its resurgance in primary liver cancer was demonstrated in three cases. PMID- 6246955 TI - Studies on the kinetics of cyanohydrin synthesis and cleavage by the the flavoenzyme oxynitrilase. AB - Almond oxynitrilase (D-alpha-hydroxynitrile lyase, EC 4.1.2.10) catalyzes the reversible condensation of HCN with aldehydes to form D-alpha-hydroxynitriles. Steady-state kinetic parameters for cleavage and synthesis of mandelonitrile and vanillin cyanohydrin were determined at pH 5.5 which is near the pH optimum of the enzyme. Benzaldehyde and vanillin act as competitive inhibitors of cyanohydrin cleavage while noncompetitive inhibition was observed for HCN. The results are consistent with an ordered uni bi mechanism in which aldehyde is the first substrate bound. Competitive inhibition of cyanohydrin cleavage was observed with various carboxylic acids, alcohols and inorganic anions. The effect of structure on the binding of these inhibitors suggests that the active site of oxynitrilase is located near a hydrophobic region and a positively charged group. Inhibitors which are reasonable analogues for cyanide anion, such as azide and thiocyanate, do not bind to the enzyme-aldehyde complex. This suggests that during cyanohydrin formation the species which binds to the enzyme-aldehyde complex is HCN rather than CN-. PMID- 6246956 TI - Purification of the bifunctional enzyme, imidazoleglycerolphosphate dehydratase histidinol phosphatase, of Salmonella typhimurium. AB - Mn2+ precipitation, antibody affinity chromatography, and selective proteolysis have been used to purify a bifunctional core of the hisB enzyme from Salmonella typhimurium. The core is homogeneous in subunit molecular weight; however, it is heterogeneous in its charge properties, probably as a result of multiple cleavage points produced by limited proteolytic digestion. The resistance of the enzyme to irreversible denaturation by urea allowed the use of urea to elute the hisB enzyme from a column of anti-hisB IgG immobilized on Sepharose. Heterogeneous oligomeric forms of the enzyme were demonstrated by electrophoretic analysis and exist as multiples of the 46,000 molecular weight monomer. PMID- 6246957 TI - Studies on in activation and reactivation of homogeneous rabbit liver phosphoprotein phosphatases by inorganic pyorphosphate and divalent cations. AB - Preincubation of two homogeneous rabbit liver phosphoprotein phosphatases (phosphophoprotein phosphohydrolases, EC 3.1.3.16) (Khandelwal, R.L., Vandenheede, J.R. and Krebs, E.G. (1976) J. Biol. Chem. 251, 4850-4858) with ATP, ADP and PPi caused a time- and concentration-dependent inactivation of the enzyme activity. A 50% inactivation of phosphoprotein phosphatase I required relatively low concentration of inactivating metabolite and less preincubation time as compared to the inactivation of phosphoprotein phosphatase II. AMP, adenosine, adenine, Pi, EDTA, EGTA, 1,10-phenanthroline and diethyl dithiocarbamate were without effect on both enzymes. Pretreatment of both enzymes by metal-chelating agents followed by PPi did not augment the effect observed with PPi alone. Both inactivated enzymes could be reactivated by cobalt or manganese in the presence of dithiothreitol. Although the extent of reactivation by these two metal ions was almost similar, cobalt required a ten times lower concentration than manganese for this process. No difference in inactivation or reactivation of both enzymes was observed with different substrates, phosphorylase a, histone or casein, employed in the assay. Pi and PPi added during the assay inhibited activities of both phosphatases with phosphorylase a and casein substrates. With histone as substrate, PPi slightly inhibited enzyme activities at lower concentrations (0.01-0.25 mM) but activated at higher concentrations. Pi activated both enzymes with this substrate; maximal activation being observed at a concentration of 5 mM. PMID- 6246959 TI - A spin labeling study of the effects of inorganic ions and pH on the conformation of spectrin. AB - The structure of spectrin from human erythrocytes has been investigated by the EPR technique measuring the mobility of the protein spin label, 4-maleimido 2,2,6,6-tetramethylpiperidinooxyl. Conformational changes in the protein induced by variation of the concentrations of NaCl, Na2SO4, KCl, CaCl2 and MgCl2 and of pH have been studied. It could be demonstrated that both Ca2+ and Mg2+ give rise to structural changes by binding to specific sites, whereas the monovalent cations (K+, Na+) seem to act via ionic strength. A model is used to correlate the spin label mobility with the radius of the protein. In the Ca2+- and Mg2+ binding experiments, the decrease in the spin label mobility has been interpreted on the basis of the theory of multiple chemical equilibria. These experiments have been compared with EPR spectra measured at different pH values. The results support the model in that binding of H+, Ca2+ or Mg2+ reduces the charges located on the protein surface: the 'discharging' reduces the repulsive forces on the surface of the molecule and consequently, the protein contracts in discrete steps. PMID- 6246958 TI - Biosynthesis of phosphatidylinositol in Crithidia fasciculata. AB - Microsomal preparations from the protozoan (Crithidia fasciculata were shown to incorporate myo-[2-3H]inositol into phosphatidylinositol by both the CDPdiacylglycerol:myo-inositol phosphatidyltransferase reaction and by a myo inositol exchange reaction. Non-ionic detergent and Mg2+ were necessary for the measurement of transferase activity. Untreated preparations could not be saturated with Mg2+, even at very high concentrations (50-75 mM). However, low concentrations of EGTA (75 micro M) both stimulated the activity 3-fold and reduced the Mg2+ required for saturation to 15-20 mM. EGTA also increased the apparent Km for CDPdiacylglycerol while increasing the sensitivity to substrate inhibition above 1 mM. The transferase activity was inhibited by relatively low concentrations of Ca2+ (50 micro M). This and the EGTA effect suggest a possible role for Ca2+ in the modulation of phosphatidylinositol synthesis. The myo inositol exchange activity required Mn2+, was insensitive to Ca2+ inhibition and was only slightly stimulated by detergents and EGTA. This activity was preferentially inactivated by heating at 50 degrees C in the presence of Triton X 100. In a detergent solubilized preparation the exchange activity but not the transferase exhibited a non-specific requirement for phospholipid. The differences in properties of the two activities suggest the presence of a separate exchange enzyme. PMID- 6246960 TI - Venom exonuclease. II. Amino acid composition and carbohydrate, metal ion and lipid content in the Crotalus adamanteus venom exonuclease. AB - Exonuclease from Crotalus adamanteus venom has only threonine as N-terminimal amono acid residue. It was examined for its amino acid composition, -SH and S-S groups. It has no free -SH groups and seven S-S bonds. The analysis of the carbohydrate residues in the enzyme proves that it is a glycoprotein. It contains neutral sugars (9.2%), amino sugars (1.9%) and ten sialic acid residues per molecule. The venom exonuclease is a metalloenzyme. This is proven by the existence of Mg2+, Zn2+ and Ca2+ and their specific role in the catalytic reactions. The enzyme contains also triacylglycerols (1.54%) and cholesterol esters (1.43%). The influence of the non-protein moieties of the exonuclease on its catalytic ability has been discussed. PMID- 6246961 TI - Small-angle X-ray scattering studies of oxidized and reduced cytochrome oxidase from Pseudomonas aeruginosa. AB - Small-angle X-rays scattering experiments were performed with oxidized and reduced cytochrome oxidase purified from Pseudomonas aeruginosa. The radii of gyration were calculated to be 40.5 A for the oxidized form and 37.0 A for the reduced. The longest dimension of the oxidized enzyme was 120 A while for the reduced it was 100 A. The volume of the oxidized protein was observed to be slightly greater than that of the reduced. These data indicate that there is a contraction of the structure of the enzyme during reduction of its constituent heme groups. PMID- 6246962 TI - The prosthetic group of methylamine dehydrogenase from Pseudomonas AM1: evidence for a quinone structure. AB - The g-value and linewidth of ESR spectra of methylamine dehydrogenase (primary amine:(acceptor) oxidoreductase (deaminating) EC 1.4.99.-) and methanol dehydrogenase (alcohol:(acceptor) oxidoreductase, EC 1.1.99.8) are very similar. This similarity is also reflected in electron-nuclear double resonance (ENDOR) results, the coupling constants of two protons in one enzyme equalling those in the other. The presence of a third proton in the ENDOR spectrum of methylamine dehydrogenase suggests a different structure or a different kind of interaction which can be related to the finding that the resolved ROSTHETIC GROUP IS PROTEIN BOUND. The bound prosthetic group has a high redox-potential, supporting the conclusion from the ESR and ENDOR results that it is a quinone derivative. PMID- 6246963 TI - Nitrogenase XII. Mossbauer studies of the MoFe protein from Clostridium pasteurianum W5. AB - We have studied the molybdenum-protein (MoFe protein) from Clostridium pasteurianum with Mossbauer spectroscopy in the temperature range from 1.5 to 200 K in magnetic fields up to 55 kG. Except for some small differences in the hyperfine parameters the results for the C. pasteurianum protein are essentially the same as those published previously for the protein from Azotobacter vinelandii, i.e. (30 +/- 2) Fe atoms partition into two identical cofactor centers M (each center most likely containing six Fe atoms and one Mo atom), four P-clusters (each center containing four Fe atoms), and one iron environment labeled S (about two Fe atoms per holoenzyme). We have analyzed the spectra of the cofactor centers in three distinct oxidation states, Formula: (see test). The diamagnetic (electronic spin S = 0) state MOX is attained by oxidation of the native, EPR-active (S = 3/2) state MN. The reduced state MR is observed in steady state under nitrogen fixing conditions; high-field Mossbauer studies show that the cofactor centers are paramagnetic (integer electronic spin S greater than or equal to 1) in the state MR. We have evaluated the complex high-field spectra resulting from the P-clusters in the oxidized state POX. The analysis shows that one iron site is characterized by a positive hyperfine coupling constant A0 while the other three sites have A0 less than 0. A slightly modified set of parameters also fits the high-field data of the MoFe protein from A. vinelandii. Finally, we will present a discussion summarizing our principle results obtained to date for the proteins from A. vinelandii and C. pasteurianum. PMID- 6246964 TI - ESR spin label studies of the nucleosome core particle and histone core. AB - An imidazole spin label has been used to study the accessibility and conformational state of tyrosines in both the nucleosome core particles and histone core extracted from chicken erythrocytes. About 40% of the tyrosyl residues in the histone core can be labeled under nondenaturing conditions. However, less than 15% of the tryosyls in the nucleosome core particle can be labeled even at 200- to 300-fold M excess of label. The effect of urea on the conformational state of the spin-labeled tyrosyls in both the nuclesome core particles and the histone core has been studied. Ionic effects on the spin labeled nucleosome core have been investigated. Several conformational transitions are observed in the range of 1 mM NaCl to 2.5 M NaCl. Three major transitions are found at 0.1 M to 0.6 M, 0.7 M to 1.8 M and 2 M to 2.5 M NaCl, respectively. The observed changes can be interpreted as swelling and conformational change of the inner histone core, gradual separation of DNA from the histone core, and tightening of the histone core. PMID- 6246965 TI - Adenosine diphosphate ribosylation of histone H1 by purified calf thymus polyadenosine diphosphate ribose polymerase. AB - The mechanism of poly ADPR synthesis and the transfer of poly ADPR to histone H1 molecule by electrophoretically homogenous calf thymus poly ADPR polymerase containing DNA was examined. 1) An acid insoluble radioactive complex (I) was obtained after incubation of purified enzyme with [3H] NAD. The stability of (I) was examined by SDS-polyacrylamide gel electrophoresis. The complex (I) was stable against acid, SDS, urea, DNase and RNase, but labile against pronase, trypsin, alkali and snake venom phosphodiesterase treatment. The molecular weight of (I) was about 130 000 daltons estimated by SDS-gel electrophoresis. The radioactive products of successive alkali, venom phosphodiesterase and Pronase hydrolysis of (I) were PR-AMP and AMP. The mean chain length of poly ADPR of (I) was 20--30. These results suggest that the complex (I) is poly ADP-ribosylated poly ADPR polymerase. 2) Besides (I), a second radioactive peak (II) was observed when acid insoluble products obtained from an incubation mixture containing purified poly ADPR polymerase, [3H] NAD and purified histone H1 were analyzed on SDS-polyacrylamide gel electrophoresis. The molecular weight of (II) was estimated to be about 23 000 daltons. The complex (II) is eluted like histone H1 on CM-cellulose columns and hydrolyzed by alkali, trypsin and snake venom phosphodiesterase but not by DNase, or RNase. The comples (II) was extracted selectively by 5 per cent perchloric acid or 5 per cent trichloroacetic acid from mixture of (I) and (II). The mean chain length of poly ADPR of complex (II) and 5 -20; these results suggest that the complex (II) is poly ADP-ribosylated histone H1. 3) Results 1) and 2) indicate that purified DNA containing, thus DNA independent, poly ADPR polymerase catalyzes two different reactions, the ADPR transfer onto the enzyme itself and onto histone H1 and the elongation of ADPR chains. Dimeric forms of ADP-ribosylated histone H1 was not observed. Free poly ADPR was observed only when very small quantities of enzyme were used for incubation. PMID- 6246966 TI - Partial purification of a normal mice serum sugar-phosphatase inhibitor from cell free ascites fluids of lymphoma-bearing mice. In vitro and in vivo effects. PMID- 6246967 TI - [Simultaneous characterizations of 3-prolylhydroxylase and 4-prolylhydroxylase activities by ion exchange chromatography]. AB - 3-prolyl hydroxylase activity measurements have already been described by Kivirikko and al, using specific methods. The aim of the present work was to show that the specific and rapid method used for 4-prolyl hydroxylase activity measurement, involving protocollagen [3H-4] proline (measuring of tritiated water enzymatically obtained), could be used for 3-prolyl hydroxylase activity estimation on the same sample: tritiated water enzymatically produced by 4-prolyl hydroxylase was collected by distillation, and the amino acids enzymatically modified were analysed after HCl 6 N hydrolysis of dried incubation medium, by cation exchange chromatography. The characterization of enzymatically obtained 3 hydroxyproline was performed using three means. The elution peaks reported were in the same position as the elution peak of pure 3-hydroxyproline and 4 hydroxyproline. Moreover, tritiated 3-hydroxyproline and 4-hydroxyproline were obtained only after incubation of labelled substrate with crude preparation of prolyl hydroxylases from chick embryos. Some possible artefacts such as dicetopiperazines and pyrrol-2-carboxylic acid have been shown to be distinguished chromatographically from 3-hydroxyproline and 4-hydroxyproline. The high ratio of measured (Formula: see text) activities, near 5.5 p. cent, is discussed. PMID- 6246968 TI - [Role of microviscosity of the lipid phase of microsomal membranes in regulation of enzymatic activity of glucose-6-phosphatase under microsomal modifications in vivo and in vitro]. AB - The changes in microviscosity of the lipid phase of microsomal membranes under microsomal modification in vivo and in vitro were studied. It was shown that in intact microsome lipids there occur five thermo-induced structural transitions within the temperature range of 5--50 degrees. Delipidation of microsomes results in a shift in structural transitions temperature. Based on the literary and own data it was assumed that the breaks on the Arrhenius plots for glucose-6 phosphatase (EC 3.1.3.9) activity are due to phase-structural changes of microsomal lipids. PMID- 6246969 TI - [Mechanisms of regulation of intracellular distribution of Ca2+ in adipose tissue]. AB - The kinetics of influx and efflux of 45Ca and its accumulation by the subcellular membranes of adipose tissue have been studied. The initial rate of Ca2+ efflux does not depend on the intracellular concentration of Na+ and K+. The rate of exchange between intracellular 45Ca and 40Ca of the incubation medium is independent on concentration of Na+ and K+ in the incubation mixture. This suggests the absence of Na,Ca-transmembrane exchange in the adipocytes. The changes in the ratio of intracellular concentration of Na+ and K+ by the factors inhibiting the activity ofNa,K-ATPase cause redistribution of Ca in the intracellular pools of the adipocytes. The lypolytic agents (adrenalin, adrenocorticotropic hormone, caffeine) but not dibutytyl-3' : 5'-AMP, accelerate Ca2+ efflux from the adipocytes. At physiological concentrations of ATP, succinate and Pi the highest Ca-accumulating activity is observed in adipose tissue mitochondria. The highest initial rate of Ca uptake, as in the case of contractile tissues, is detected in the endoplasmic reticulum membranes. In contrast to the plasma membranes and reticulum, in which the Ca-accumulating capacity is independent of ATP concentration up to 0.5 mM, the Ca-accumulating capacity of mitochondria decreases 8--9-fold with a reduction in ATP concentration from 4 down to 1 mM. The physiological significance of this phenomenon in the action mechanism of lipolytic agents, which reduce the ATP content in the adipocytes, is discussed. PMID- 6246970 TI - [Comparative characteristics of membrane-bound and solubilized 3':5'-AMP dependent protein kinase from myocardium sarcoplasmic reticulum membranes]. AB - A kinetic study of membrane-bound and solubilized 3' : 5'-AMP-dependent protein kinase from rabbit myocardium sarcoplasmic reticulum membranes was carried out. Both enzyme preparations catalyzed the phosphorylation of exogenous protein substrates (histones) and endogenous membrane substrate. Solubilization of protein kinase and its subsequent purification on columns with DEAE-cellulose and hydroxyapatite did not change the substrate specificity and kinetic properties of the enzyme. Both preparations differed in the maximal rates of the reaction; the differences in apparent Km values for ATP and histone H1 were insignificant. The membrane-bound and solubilized preparations had the same pH optimum of 6,5. Their maximum activity was exerted at Mg2+ concentration considerably exceeding that of ATP. Ca2+ at micromolar concentrations had no effect on the enzyme activity. PMID- 6246971 TI - [Properties of aminoglycoside-3'-phosphotransferases determined by kanamycin transposones Tn 601 and Tn 5]. AB - Aminoglycoside-3'-phosphotransferase I and II (APT-3'-I and APT-3'-II) has been purified to homogenity from the cells of E. coli containing the plasmids R6 and JR67, respectively. The purification procedure involved competitive affinity chromatography on neomycin-sepharose and gel-filtration on Sephadex G-100. The specific activity of APT-3'-I with the substrates--lividomycin A, neomycin B, paromycin, ribostamycin, kanamycins A and B--are 4.3, 2.8, 2.1, 1.6, 0.9 and 0.8 mol/min. mg protein, respectively. The specific activity of APT-3'-II with the substrates--ribostamycin, paromycin, kanamycins A and B, neomycin B--are 8.0, 7.2, 4.0, 4.5 and 3.6, respectively. Mg2+ is required for the activity of both enzymes. Co2+, Zn2+ and Mn2+ are active in case of APT-3'-I; however, these cations are less active than Mg2+. The pH-optimum of APT-3'-I and APT-3'-II is 7.0--7.5. High ionic strength is required for the activity of both enzymes. The molecular weights of APT-3'-I and APT-3'-II are about 36 000 and 26 000, respectively. The amino acid composition of APT-3'-I and APT-3'-II was determined. Both enzymes contain tryptophane residues whose fluorescence intensity decreased when ATP, but not amino-glycoside antibiotics, is added. The interrelationship between the molecular weights of these enzymes and the sizes of the loops of transposones Tn 601 and Tn 5, encoding APT-3'-I and APT-3'-II, is discussed. PMID- 6246972 TI - [Conformational changes of spin-labeled native and modified phosphorylase B]. AB - The phosphorylase B labelled with 2,2,6,6-tetramethyl-piperidine-1-oxyl-4 iodacetamide (phosphorylase I) and with 2,2,6,6-tetramethyl-piperidine-1-oxyl-4 ethylmaleinimide (phosphorylase II) was studied. It was shown that label I is characterized by a greater mobility with respect to the protein as compared to label II. In spin-labelled preparations of phosphorylase B the 1,5--2,0 SH-groups of the enzyme monomer having no effect on the enzyme activity were modified. The effects of AMP, glucose-1-phosphate and glucose-6-phosphate on the EPR spectrum of phosphorylase I were studied. The greatest changes in the spectrum (especially in the high field line) were found to occur in the presence of glucose-6 phosphate. These changes are due to the increase in the degree of anisotropic spin rotation. The experimental and theoretical spectra allowing to determine the correlation time for the protein moiety (tau b = 160 ns) were shown to be similar. The local conformation changes were found to occur in the vicinity of one of the two label-bound SH-groups of phosphorylase I. The EPR spectra demonstrate the S-shaped dependence of mobility of phosphorylase I label on concentration of glucose-6-phosphate (0,1--10 mM). In the presence of AMP no S shaped dependence is observed. Reduced NaBH4 phosphorylase I does not reveal the S-shaped dependence of the label mobility on concentration of glucose-6 phosphate. The degree of the label immobilization in the apo-phosphorylase I- pyridoxal-5-chloromethylphosphonate complex in the presence of glucose-6 phosphate and AMP is the same as in cholophosphorylase I; however, in contrast to the choloenzyme it does not depend on glucose-6-phosphate (0,1--10,0 mM). The changes in the mobility of the spin label of apophosphorylase I and its complex with the AMP analog--adenosine-5'-chloromethylphosphonate--during the choloenzyme reconstruction by pyridoxalphosphate are indicative of participation of AMP and the phosphate group of AMP in the formation of the enzyme active center. PMID- 6246973 TI - [Cause of increase in the efficiency of Ca2+ transport by fragments of sarcoplasmic reticulum from fast skeletal muscles induced by protein kinase]. AB - The effect of cAMP-dependent protein kinases from rabbit skeletal muscles on Ca2+ uptake by fragments of skeletal muscle sarcoplasmic reticulum was studied. It was shown that incubation of the sarcoplasmic reticulum fragments with protein kinase increases the rate of Ca2+ uptake without changing the activity of Ca2+-dependent ATPase. This phenomenon is not accompanied by phosphorus incorporation into the protein components of the reticulum membranes. The protein kinase preparation subjected to "self-phosphorylation" is also capable to increase the rate of Ca2+ uptake. Using (14C) -oleic acid, it was shown that the increase of the rate of Ca2+ transport under effects of the "self-phosphorylated" protein kinase occurs due to the binding of free fatty acids present in the sarcoplasmic reticulum membranes. It was found that the effect observed is due to phosphofructokinase (ATP : D-fructose-6-phosphate-1-phosphotransferase) present in the protein kinase preparation. PMID- 6246974 TI - [Activity of protein kinases and phosphodiesterases in the cell cycle of Ph. polycephalum]. PMID- 6246975 TI - [Autophosphorylation of cyclic AMP-dependent protein kinase from pig brain]. AB - Autophosphorylation of cyclic AMP-dependent pig brain protein kinase has been detected. Up to 1,5 moles of gamma-32P are transferred from [gamma-32P]ATP to the dimer of the regulatory subunit. The autophosphorylation reaction is Mg2+ dependent and occurs at a high rate: more than 50% of the radioactive label is incorporated during the first minute of incubation at 30 degrees. The pH dependence of this reaction differs from that of the phosphotransferase reaction. The phosphoholoenzyme is more sensitive to cyclic AMP than the dephosphoholoenzyme; however, both forms bind up to 2 moles of 3H-cyclic AMP per 1 mole of the holoenzyme. The activation and dissociation constants for both forms of the holoenzyme have been calculated. The autophosphorylation reaction has been shown to occur via an intramolecular mechanism; the phosphorylation of the regulatory subunit can occur only within the holoenzyme. The increase in the concentration of cyclic AMP causes the latter to produce an inhibitory effect on autophosphorylation. The regulatory action of autophosphorylation on cyclic AMP dependent protein kinases is discussed. PMID- 6246976 TI - [Membrane regulation of brain Na,K-ATPase inhibition by calcium ions]. AB - In contrast to the purified enzyme. Na, K-ATPase from intact synaptic membranes is inhibited by Ca2+ according to a biphase pattern at Ca2+ concentrations of 10( 6) to 10(-3) M. The membrane damage after three washings with bidistilled water results in elimination of low cocentration phase. Recombination of the sediment and the supernatant restores the initial shape of the inhibition curve. Dithiothreitol greatly increases the inhibition by low Ca concentrations. This effect is absent in the purified enzyme preparation and is considerably reduced after the membrane damage. Recombination restores the dithiothreitol effect. It is suggested that the sensitivity of membrane Na,K-ATPase to low concentrations of Ca2+ is controlled by the components (most likely, peripheral proteins), which are loosely bound to the membrane, this process being dependent on the degree of the SH-group reduction. PMID- 6246977 TI - [Structural-functional state of Ca-transport system of sarcoplasmic reticulum membranes after deep freezing]. AB - The structure and functions of the Ca-transport system of sarcoplasmic reticulum (SR) at low temperatures (-5--196 degrees) were studied. It was shown that during SR freezing-thawing the activation energy of ATP enzymatic hydrolysis as well as the Ca-ATPase sensitivity to calcium ions were changed. The Km value for the carrier seemed to be unaffected thereby. Using the EPR method it was shown that after freezing down to -196 degrees and a subsequent thawing the protein-lipil interactions and the orderliness of phospholipid fatty acid chains in the SR membranes were altered. On the contrary, the activity of Ca-ATPase isolated from SR membranes remained unchanged, which is indicative of the enzyme resistance to the cold. The mechanisms responsible for the impairment of the functioning of Ca transport system of SR membranes due to freezing are discussed. PMID- 6246978 TI - [Light-induced changes in activity of Na, K-ATPase from the retinal photoreceptors of vertebrates: possible mechanism]. AB - The mechanism of light-induced changes in the activity of Na,K-ATPase from plasma membranes (PM) of photoreceptor cells was studied in vitro. Illumination resulted in inhibition of the ATPase activity and an increase of 18O exchange between water and Pi. The maximum light effect was revealed when the PM contained both the inner segments of the rods (RIS) and rod outer segments (ROS) of the photoreceptor cells. Lipid peroxidation stimulated by the FeSO4+ascorbate system induced a decrease of the ATPase activity. Antioxidants (ionol, Na2SeO3, vitamin E) prevented the effect of the lipid peroxidation products on NA,K-ATPase and the photoinduced changes of the enzyme activity. It is supposed that the photoinduced changes of the Na,K-ATPase activity in vitro are due to lipid peroxidation of photoreceptor PM. PMID- 6246979 TI - [Thermal denaturation and nuclease degradation of complexes of stellins A and B with DNA]. AB - The soluble complexes of stellins A and B-protamines from Acipenser stellatus with DNA were obtained by direct mixing in 2,5.10(-4) M EDTA, pH 8,0. The differential curves of melting of the complexes reveal two transitions at Tmelt.1=49+/-1 degree and Tmelt.2=90+/-1 degree, corresponding to melting of DNA regions of free and protamine-bound DNA regions. The number of amino acid residues per one nucleotide in the protein-binding sites of DNA is 1,30 and 1,22 for the stellin A- and stellin B-DNA complexes, respectively. It was demonstrated that under denaturation the DNA filaments do not break apart completely. Data from the analysis of products of the complexes hydrolysis by DNAse I allowed to postulate a selective binding of the protamines to the AT-pairs of DNA. This assumption was confirmed by changes in the melting curves under different protein/DNA ratios. PMID- 6246980 TI - [Expression of the restriction fragment of phage T7 DNA in a cell-free transcription-translation system from E. coli]. AB - The matrix activity of phage T7 DNA and the restriction fragment of phage T7 DNA containing gene 0,3 with a promoter was studied with respect to RNA and protein syntheses in a cell-free transcription-translation system from E. coli. A comparison of the protein products of cell-free synthesis was carried out, using polyacrylamide gel electrophoresis and a subsequent radiofluorography. Data from PAAG suggest that the restriction fragment codes the synthesis of a polypeptide, whose size is identical to that of a polypeptide synthesized on a corresponding gene in phage T7 DNA. A possible use of the cell-free system of coupled transcription-translation for the functional mapping of the genome DNA is discussed. PMID- 6246981 TI - [Effects of some protein kinases, cyclic nucleotides and specific inhibitors of phosphorylation on the mitotic cycle of Physarum polycephalum]. AB - The true slime mould Physarum polycephalum was treated with various agents by spraying them upon the cell surface 4 hrs before the second synchronous mitosis. The onset of mitosis was considerably approximated after the plasmodium treatment with protein kinases from rat hepatoma or Ph. polycephalum at the late G2 phase. The catalytic and regulatory subunits of cAMP-dependent pig brain protein kinase caused retardation of mitosis, while the holoenzyme, casein kinase and alkaline phosphatase did not affect the timing of mitosis. The cyclic nucleotides and inhibitors of their metabolic enzymes were used to investigate the role of phosphorylation processes in the mitotic cycle. PMID- 6246982 TI - [Cyclic AMP-dependent pig brain protein kinase: subunit structure, mechanism of autophosphorylation and holoenzyme dissociation under cyclic AMP action]. AB - Some properties of cyclic AMP-dependent pig brain protein kinase were studied. The holoenzyme was shown to exist in solution in the form of a tetramer complex R2C2 with mol. weight of 180 000. The limited proteolysis of the regulatory subunit caused the formation of a fragment with mol. weight of 35 000, capable of independent binding of 3H-cyclic AMP and containing a site, which can be phosphorylated in the autophosphorylation reaction. Autophosphorylation of the holoenzyme led to an increase in the degree of dissociation of the former into individual subunits under the effect of cyclic AMP. The ability of the phosphoform of the catalytic subunit was demonstrated. The autophosphorylation process and the phosphotransferase reaction involve the same active site of the catalytic subunit. PMID- 6246983 TI - [Two ways of formate oxidation in methylotrophic bacteria]. AB - The cells of Achromobacter parvulus, strain 1T, when grown in a methanol containing medium, have two formate dehydrogenases, i.e. NAD-linked formate dehydrogenase and the formate dehydrogenase reducing the ferricyanide and tetrazolia. Only the latter enzyme was found in the cells grown in a medium with glycerol as a carbon source. These enzymes differ with respect to Km for formate and antigenic specificity. Km for formate oxidation by the cells of A. parvulus is lower than for formate of the NAD-dependent formate dehydrogenase and is equal to Km for the enzyme reducing artificial electron acceptors. The results obtained are discussed in terms of the existence of two cytochrome oxidase systems in the methylotrophic bacteria, differing in their sensitivities to the inhibition by formate. PMID- 6246984 TI - [Distribution of 5'-nucleotidase activity in the subcellular fractions of rabbit brain cortex]. AB - The specific activity of 5'-nucleotidase was measured in the fractions of myelin, synaptic membranes, heavy and light synaptosomes and purified mitochondria of brain cortex of intact rabbits. The enzyme specific activity in these fractions was practically the same and made up to 2.2, 2.1, 1.98 and 1.8 mkmoles of Pn per mg of protein per hr. The differences between the specific activities of the four fractions were statistically insignificant. The 5'-nucleotidase activity of the heavy synaptosome fraction was 2 times as low as that of the other fractions as was equal to 0.92 mkmoles of Pn per mg of protein per hr. This value is statistically different from those obtained during the analysis of the other fractions. PMID- 6246985 TI - Cyclic AMP and contractility of the human oviduct. PMID- 6246986 TI - Alterations in the number of ovine luteal receptors of LH and progesterone secretion induced by homologous hormone. PMID- 6246987 TI - Immunocytochemical localization of cyclic AMP and cyclic GMP in rat ovarian tissue. PMID- 6246988 TI - Cyclic AMP, prostaglandin E2 and steroids: possible mediators in the rat cumulus oophorus mucification. PMID- 6246989 TI - A general method for biological inference: illustrated by the estimation of gene nucleotide transition probabilities. AB - The method of maximum entropy inference developed by Jaynes can be a particularly useful method for obtaining unbiased estimates of biological parameters when the experimental knowledge about a system can be explicitly formulated. Base transition probabilities between genes, though central to evolutionary theory and understanding, present a difficult estimation problem because the ancestral genes are not experimentally accessible. The necessary estimates must therefore be made on the basis of experimental knowledge other than a direct frequency count of base replacements (A leads to C, for example) between contemporary genes. It is shown how maximum entropy inference together with the experimentally observed fact of compositional fidelity in a given gene family can be used to obtain meaningful gene base transition probabilities at each of the three nucleotide positions within codons. Both symmetric and asymmetric transition probabilities are considered. Tables of these probabilities are given for each codon position for the alpha-hemoglobin, beta-hemoglobin, myoglobin, cytochrome c, and the parvalbumin group genes. Tabular values of the average amino acid composition of these five protein families and the average nucleotide composition of their coding genes at varied codon loci are given. It is thus no longer necessary to assume in theories of evolutionary divergence equimolar base ratios A:C:G:U::1:1:1:1 or that each base has an equal chance of mutating to and being fixed as any one of the other three bases. PMID- 6246990 TI - [Quantitative histochemical study of alkaline phosphatase isoenzymes in the uteri of ovariectomized golden hamsters during estrogenization]. AB - The activity of two isoenzymes of alkaline phosphatase was studied in the uteri of ovariectomized golden hamsters. Animals belonging to different groups were daily injected with 10 micrograms of estrogen (octoestrol) once, for 4 and 16 days. The estrogen did not affect the overall activity lf alkaline phosphatase in the uterine luminal epithelium, but decreased the enzyme activity in stroma. Moreover, it was found that prolonged estrogen treatment increases significantly the proportion of alkaline phosphatase isoenzyme of the intestinal type in the uterine luminal epithelium. PMID- 6246991 TI - [Electron microscopic study of the tissue reaction of lungs exposed to quartz dust of varying dispersity]. AB - The tissue reaction of the lungs exposed to quartz dust of varying dispersity was studied by light, transmission and scanning electron microscopy. It is suggested that specific clinical manifestations of dust pathology are related to dispersity of silica. The largest quartz-containing dust particles give rise chiefly to the development of dust bronchitis. The most cytotoxic "medium" fractions lead to appearance of nodular forms of silicosis, whereas highly dispersed dust particles of quartz give rise to the development of diffusive sclerotic changes in the lungs. PMID- 6246992 TI - An oxygen-dependent mechanism of neutrophil-mediated cytotoxicity. AB - Human neutophils stimulated with phorbol myristate acetate were able to rapidly destroy autologous red blood cell targets. Neutrophil-mediated cytotoxicity was related to phorbol myristate acetate concentration and neutrophil number. The ability of stimulated neutrophils to lyse red blood cell targets was markedly impaired by catalase or superoxide dismutase but not by heat-inactivated enzymes or albumin. Despite a simultaneous requirement for O2.- and H2O2 in the cytotoxic event, a variety of OH. and 1O2 did not effect cytolysis. The myeloperoxidase inhibitor cyanide did not reduce red blood destruction, while azide consistently impaired cytolysis. The inability of cyanide to reduce cytotoxicity coupled with the protective effect of superoxide dismutase suggests that cytotoxicity is independent of the classic myeloperoxidase-H2O2-halide system. We propose that neutrophils, stimulated with phorbol myristate acetate, generate O2.- and H2O2, which play an integral role in a novel cytotoxic mechanism. PMID- 6246993 TI - Complement sensitivity of paroxysmal nocturnal hemoglobinuria bone marrow cells. AB - Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired disorder in which erythrocytes, granulocytes, and platelets are defective, as shown by increased susceptibility of RBCs, WBCs, and platelets to complement-mediated lysis in vitro. The purpose of this study is to determine the sensitivity to complement lysis of PNH and non-PNH erythroid and myeloid precursors using the release of 59Fe and myeloperoxidase as specific markers to monitor the lytic action of complement on erythroid and myeloid cell precursors, respectively. Erythroid cell precursors in four of four PNH patients demonstrated increased sensitivity to complement-mediated lysis. Myeloid cell precursors in four of five PNH patients also exhibited increased sensitivity to complement and antibody. In addition, CFU c growth was below normal in the marrow of seven PNH patients. These findings support the hypothesis that the defect in PNH occurs at the level of the hematopoietic stem cell. PMID- 6246994 TI - The detection and use of hemoglobin mutants in the direct analysis of human globin genes. AB - Many human globin-chain mutants contain amino acid replacements that result from single base changes in the corresponding globin gene. Using recombinants, the coding sequences of each of the alpha-, beta-, Ggamma-, and Agamma-globin genes have now been determined. Those sequences of DNA that are cleaved by a number of specific restriction endonucleases have been identified and accurately positioned. Mutations at these sequences abolish the restriction site, and therefore, the pattern of DNA fragments containing hybridizing globin-gene sequences is altered compared to DNA from normal persons. This allows the identification of one of a pair of cross-hybridizing human globin-gene sequences, as is shown here for the two alpha-globin, the two gamma-globin, and the delta- and beta-globin genes. PMID- 6246995 TI - Unequal crossing-over: a common basis of single alpha-globin genes in Asians and American blacks with hemoglobin-H disease. AB - The alpha-globin genes of five black Americans, two Chinese, and five Filipinos with HbH disease (an alpha-thalassemia state in which there is a single functional alpha gene) were analyzed by restriction endonuclease techniques. All subjects were found to have one chromosome 16, lacking both alpha genes, and another containing a single alpha gene (--/-alpha). Restriction endonuclease patterns of the DNA obtained from all 12 subjects were identical and compatible with unequal crossing-over as the mechanism of origin of the single alpha gene in these individuals. PMID- 6246996 TI - Biochemical characterization of a leukemia-associated inhibitor (LAI) suppressing normal granulopoiesis in vitro. AB - Low-density (less than 1.077 g/ml) marrow or blood cells from patients with acute or chronic leukemia release a high molecular weight substance called "leukemia associated inhibitor" (LAI) that reduces the fraction of normal marrow CFU-c in S phase as measured with the 3H-TdR suicide technique. LAI from conditioned media or 3M KCl extracts of subcellular fractions behaved homogeneously on gel chromatography, showing an apparent molecular weight greater than 500,000. However, ion-exchange chromatography and isoelectric focusing indicated considerable charge heterogeneity for LAI molecules. Results from SDS polyacrylamide gel electrophoresis indicated that the biologic activity resides in a subunit of 150,000-170,000 daltons. The findings of marked affinity for Con A-Sepharose, marked susceptibility to mild periodate treatment, partial susceptibility to protease digestion, and relative resistance to heating suggest that LAI is a glycoprotein. Data from radiolabeling of cell surface components and sucrose density gradient centrifugation are consistent with LAI being a peripheral cell membrane glycoprotein, which may suppress normal granulopoiesis in leukemia. PMID- 6246997 TI - Topographic organization of nerve fields. PMID- 6246998 TI - Thorotrast-induced multiple carcinomatosis of the frontal sinus. PMID- 6246999 TI - The usefulness of cytology. PMID- 6247000 TI - Effects of endorphins on different parts of the gastrointestinal tract of rat and guinea-pig in vitro. AB - 1 The spasmogenic and spasmolytic effects of beta-lipotropin (LPH) fragments and one analogue were investigated on different parts of the gastro-intestinal tract of guinea-pig and rat in vitro.2 Changes in muscle tone were observed in colon and rectum and to a lesser extent in jejunum and ileum of both species. Rat colon and rectum contracted to the peptides. Guinea-pig colon and rectum relaxed after an initial short-lasting contraction.3 On the rat rectum (D-ala(2))met enkephalin, leu-enkephalin, gamma-endorphin, alpha-endorphin and beta-LPH 80-91 caused dose-dependent contractions, their ED(50) values being 0.96 x 10(-12) mol, 1.05 x 10(-11) mol, 1.22 x 10(-11) mol, 1.08 x 10(-10) mol, 2.65 x 10(-10) mol and 6.5 x 10(-9) mol, respectively.4 Naloxone dose-dependently shifted the dose response curve of met-enkephalin to the right. Atropine, hexamethonium, burimamide, mepyramine, propranolol and indomethacin did not influence the response to met-enkephalin.5 In the presence of tetrodotoxin, the ED(50) for met enkephalin and the maximal contractor response induced by met-enkephalin, appeared to be increased.6 The 5-hydroxytryptamine (5-HT) antagonists, methysergide and cyproheptadine, reduced the contractor response in a non competitive manner. The alpha-adrenoceptor antagonist phentolamine, in contrast, caused an increase of the maximal response to met-enkephalin of up to 200%. Noradrenergic and tryptaminergic systems, therefore, might be involved in the changes in muscle tone induced by met-enkephalin.7 These results demonstrate that rectum and colon of guinea-pig and rat are very sensitive to opioid-like peptides. PMID- 6247001 TI - Chemokinesis of rat polymorphonuclear leucocytes and the effect of cyclic adenosine 3',5'-monophosphate. AB - 1 The chemotactic and chemokinetic properties of various substances were studied using rat polymorphonuclear leucocytes (PMN) in Boyden chambers. 2 Casein and the exudate from a carrageenan-induced pleurisy possessed both chemotactic and chemokinetic properties, whereas erythrocyte lysates and albumin showed only chemokinetic activity. 3 Dibutyryl cyclic adenosine 3',5'-monophosphate (db cyclic AMP) had little or no effect on the migration towards casein and the inflammatory ecudate, but stimulated the migration towards erythrocyte lysates and albumin. 4 It appears therefore that db cyclic AMP is able to increase a chemokinetic response initiated by other substances. The lack of effect of this compound on cell migration towards substances possessing both chemotactic and chemokinetic properties probably results from the equilibrating effect of a simultaneous stimulation of chemokinesis and inhibition of chemotaxis. 5 These results suggest that studies designed to investigate the effect of anti inflammatory drugs on cell migration should include the separate assessment of their ability to influence both chemotaxis and chemokinesis. PMID- 6247002 TI - Beta 2-adrenoceptors mediate the stimulating effect of adrenaline on active electrogenic Na-K-transport in rat soleus muscle. AB - The relative role of beta 1- and beta 2-adrenoceptors in mediating the stimulating effect of adrenaline on active electrogenic Na-K-transport has been assessed in experiments on rat soleus muscles in vitro and in vivo. 2 In the rat isolated soleus muscle, adrenaline (10(-6) M) increases the resting membrane potential (EM) by 5.8 mV and stimulates 22Na-efflux and ouabain-suppressible 42K uptake by 91 and 94%, respectively. 3 All of these effects are completely blocked by propranolol (10(-5) M), whereas the beta 1-selective adrenoceptor antagonist, metoprolol, was found to be at least 50 times less potent. 4 The beta 2 adrenoceptor agonist, salbutamol, was at least 100 times as potent as H133/22 (a beta 1-selective agonist) in stimulating 22Na-efflux and 42K-influx. 5 In experiments performed under pentobarbitone anaesthesia, the intravenous injection of adrenaline (5 microgram) or salbutamol (0.5 to 50 microgram) led to a rapid and marked increase in the EM of the exposed soleus muscle. This hyperpolarizing effect could not be accounted for by the concomitant, relatively modest change in extracellular K. PMID- 6247003 TI - Presynaptic and postsynaptic depressant effects of phenytoin sodium at the neuromuscular junction. AB - 1. Phenytoin sodium, 10 micrograms/ml (3.6 x 10(-5) M), reduces the amplitude of endplate potentials in mouse sternomastoid neuromuscular junctions. 2. The reduction in amplitude is due to a reduction both in the quantal content of endplate potentials and in the amplitude of the voltage response to quanta of acetylcholine. 3. The reduction caused by phenytoin in the amplitude of spontaneous miniature end plate potentials was due to a reduction in the time constant of decay of miniature endplate currents. 4. It is concluded that phenytoin depresses neuromuscular transmission by reducing both the amount of acetylcholine secreted in response to an action potential and by reducing the lifetime of postsynaptic channels activated by acetylcholine. PMID- 6247004 TI - Diabetogenic effects of chronic oral cadmium adminstration to neonatal rats. AB - 1 Chronic exposure of neonatal rats to oral cadmium (Cd) (0.1 and 1.0 micrograms/g daily for 45 days) disturbed glucose homeostasis, as reflected by hyperglycaemia, reduced liver glycogen and enhanced gluconeogenic potential of hepatic tissue. 2 This Cd-exposure regimen also increased hepatic cyclic adenosine 3',5'-monophosphate (cyclic AMP) which was accompanied by enhancement of basal, adrenaline and glucagon-stimulated form(s) of adenylate cyclase. 3 In order to assess the responsiveness of pancreatic beta cells to glucose, islets isolated from control as well as Cd-exposed animals were incubated in vitro and their rate of insulin secretion determined. In the presence of glucose 0.5 mg/ml, there was no significant difference in the rate of insulin release. However, at higher glucose concentrations (1.5 and 3.0 mg/ml), the islets from Cd-exposed rats released significantly less insulin than those of control animals. 4 The results are discussed in relation to the possible mechanism of the diabetogenic effect of Cd. PMID- 6247005 TI - Adenine nucleotides and synaptic transmission in the in vitro rat hippocampus. AB - 1 The effects of adenosine and various derivatives were examined in the in vitro hippocampal slice preparation from rat.2 The amplitudes of extracellularly recorded field potentials from the CA1 region were depressed by adenosine, and this effect could be antagonized by methylxanthines. Because presynaptic field potentials were unaffected by adenosine, while the field e.p.s.p. was depressed, adenosine would appear to act at a synaptic site to depress transmission.3 Adenosine deaminase, which breaks down adenosine to inosine, increased the amplitude of synaptic responses, while hexobendine, which blocks reuptake of adenosine, had a depressant effect. This strongly suggests that the endogenous release of adenosine from the hippocampal slice preparation is sufficient to exert a tonic inhibitory influence on the amplitude of synaptic responses.4 Cyclic adenosine 3',5'-monophosphate (cyclic AMP) and its dibutyryl derivative had depressant effects on the amplitude of field responses which were blocked by theophylline, suggesting that they are able to act at the extracellular adenosine receptor. (-)-Isoprenaline (which raises tissue cyclic AMP levels), and the 8-p chlorophenylthio derivative of cyclic AMP both increased the amplitude of population spike responses, and these effects were not blocked by theophylline, suggesting that the physiological effects of adenosine are not mediated via a cyclic AMP-dependent mechanism.5 Since adenosine is not the transmitter at this CA1 pyramidal cell synapse, but is apparently present in the extracellular compartment in sufficient concentrations to affect the synaptic physiology of this region, this provides strong evidence in favour of the concept of a neuromodulatory role for adenosine in the central nervous system. PMID- 6247006 TI - Increase in epithelial cyclic adenosine 3',5'-monophosphate following vanadate. AB - Vanadate increases the cyclic adenosine 3',5'-monophosphate (cyclic AMP) content of frog skin epithelium and apparently antagonizes the stimulation by isoprenaline. The effect appears to be a direct activation of adenyl cyclase. This new effect of vanadate together with the inhibitory effects on Na-K ATPase may explain the irregular effects on sodium transport. PMID- 6247007 TI - Identification of GABA neurons in rat cortical cultures by GABA uptake autoradiography. AB - Autoradiographic studies of rat cortical cultures were conducted with tritiated transmitters and related drugs. Autoradiographs prepared from cultures incubated in [3H]GABA showed selective labeling: dense accumulations of silver grains over the somas and all processes of approximately 30-50% of the neuronal population, few grains over the non-neuronal cells. This labeling was blocked by diaminobutyric acid (DABA) and sodium-free media but not by beta-alanine and thus has the characteristics of GABA uptake in other neuronal systems. There were no obvious differences in the size, shape, number of processes or distribution in the culture between neurons which accumulated GABA and those which did not. Similar cultures incubated in either [3H]glycine or [3H]glutamate and processed by autoradiography resulted in a much different distribution of silver grains than that seen for [3H]GABA. Following incubation in [3H]glycine, silver grains were distributed uniformly over all cells in the culture, both neuronal and non neuronal. This distribution suggests a metabolic and not a neurotransmitter role for glycine in the cultures, as would be expected of neuronal cells derived from cerebral cortex. Glutamate incubations resulted in the appearance of silver grains over only the non-neuronal cells with very few over the neuronal population. Autoradiograms were also prepared following incubation in the potent GABA receptor agonist [3H]muscimol. These autoradiograms were indistinguishable from those obtained following [3H]GABA incubation. Thus, a finite population of neurons was densely labeled, the labeling was blocked by the GABA uptake inhibitors DABA, nipecotic acid, guvacine and Na+-free media, while substances which interact with the GABA receptor, bicuculline methiodide, THIP, isoguvacine and the noncompetitive antagonist, picrotoxin, were without effect. These results demonstrate that the affinity of muscimol for the GABA uptake site far outweighs its affinity for the GABA receptor site in autoradiographic experiments where intact cells are employed, presumably because its binding to receptors is fleeting. Therefore, muscimol autoradiography may not be informative about GABA receptor localization. These autoradiographic studies suggest that nearly half the neurons in our culture system are GABA neurons but disclosed no morphological handle for GABA neurons. PMID- 6247008 TI - Immunohistochemical localization of enkephalin in rat forebrain. AB - Discrete localization of enkephalin immunoreactive sites in the rat forebrain was undertaken using animals with and without colchicine pretreatment. Both the immunofluorescence and unlabeled PAP antibody techniques were employed using antisera directed against methionine-enkephalin. We have found several areas of enkephalin fiber and cell localizations not previously described, as well as confirming the results of other researchers. Thus, we found large amounts of perikaryal enkephalin immunoreactivity in the lateral septal nucleus, bed nucleus of the stria terminalis, the preoptic nuclei, the ventral premammillary nucleus, prelateral mammillary nucleus, the medial mammillary nucleus, paraventricular nucleus, the periventricular, ventromedial, dorsomedial and posterior nuclei of the hypothalamus, the arcuate nucleus, and the ventral nucleus of the lateral geniculate body. High concentrations of immunoreactive neuronal fibers not immediately associated with enkephalin perikarya were seen in the nucleus accumbens, medial forebrain bundle, globus pallidus, mammillothalamic tract, the subthalamic nucleus, and the caudal portion of the zona incerta. Many of the areas presented in this study correspond with areas known to exert some regulation over neuroendocrine function as well as various motor and sensory functions. Nuclei with high immunoreactive fiber content also correspond in many instances with areas reported to have high concentrations of opiate receptors. Possible enkephalin-containing tracts and the relationships of enkephalin containing cells in fiber bundles are also pointed out. PMID- 6247009 TI - Electrophysiological study on the postnatal development of mitral cell activity in the rat olfactory bulb. PMID- 6247010 TI - Ontogeny of alpha 1 and alpha 2-adrenoceptors in rat brain. PMID- 6247011 TI - Brain angiotensin II receptor affinity and capacity in SHR and WKY rats: effects of acute dietary changes in NaCl. PMID- 6247012 TI - The effects of pentobarbital and related compounds on frog motoneurons. AB - The effect of pentobarbital (PB) and related compounds on frog motoneurons was examined with sucrose gap recording from the ventral roots. PB was found to: (1) depress the action of glutamate, (2) selectively enhance the action of GABA, (3) reverse the non-competitive picrotoxin antagonism of GABA and the competitive strychnine antagonism of beta-alanine, but not the competitive bicuculline methiodide antagonism of GABA, and (4) elicit a GABAmimetic hyperpolarization. The first three actions had a threshold concentration of 10 microM, while the GABAmimetic action required a 10-fold higher concentration. The reversal of picrotoxin's action by PB suggests that PB might modify GABA mechanisms by combining to the picrotoxin recognition site. Phenobarbital shared all of the properties of PB but was approximately one-fifth as potent. The only property that phenytoin shared with PB was a weak depression of glutamate responses. Chlordiazepoxide selectively enhanced GABA responses but was devoid of the other actions of PB. These results suggest that the GABAmimetic effect of PB may be an important feature in the depressant and anesthetic properties of PB. The anesthetic chloralose, which is structurally unrelated to PB, nevertheless shared all of the actions of PB. This finding suggests that the properties described for PB may also be found in other general anesthetics. PMID- 6247013 TI - Endorphin-mediated inhibition of locus coeruleus neurons. PMID- 6247014 TI - Met-enkephalin levels and opiate receptors in the spinal cord of chronic suffering rats. PMID- 6247015 TI - Excitability of bulbar respiratory neurones: a study using microiontophoretic applications of depolarizing agents. AB - The discharge of cat's bulbar respiratory neurones (RN) was shown to be modulated by periodic depressions which are characterized by their ability to reduce the effectiveness of microiontophoretically applied depolarizing agents: L-glutamate, acetylcholine and potassium. From the observation of cycle triggered time histograms (CTH), it appeared that these depressions have a determined and invariable phase relationship within the respiratory cycle. They were demonstrated in RN histologically located between and including the nucleus of the tractus solitarius and the nucleus ambiguus. Reproducibility and dose/response relationship of L-glutamate-induced depolarizations enabled an estimation of the functional effectiveness of these periodic depressions. In spontaneously phasic or 'silent' RN, depressions were demonstrated in the majority of cases (71%). Strongest depressions prevented spontaneous and L glutamate-induced firing. Slighter depressions did not completely abolish L glutamate effectiveness but reduced it by 20-90%. Conversely, in the majority of spontaneously tonic units (68%) depressions were not identified since the L glutamate effect remained unchanged throughout the respiratory cycle. Four types of these respiration-related depressions were differentiated on the basis of their length, their phase relation to the respiratory cycle and their potentiation in barbiturate-anaesthetized preparations. A first type suppressed L glutamate-evoked firing throughout inspiration; it was found in late-expiratory neurones. Two other types of depressions had a more restricted duration in the cycle: one was restricted to a portion of inspiration and was found in early expiratory neurones; the other restricted to the beginning of expiration, was found in a special group of inspiratory neurones. A fourth type of inhibition was weaker and actively prolonged throughout expiration: it was found in another group of inspiratory neurones including the respiratory neurones located at the level of the nucleus of the tractus solitarius. These periodic depressions are interpreted in terms of synaptic inhibition; it is proposed that they play a major role in the functional organization of the respiratory centers at the bulbar level. PMID- 6247016 TI - Ionic permeabilities of the frog perineurium. AB - Ionic permeation was investigated across the perineurium of the frog sciatic nerve, under normal conditions and following treatment by hypertonic Ringer, ouabain or amiloride. A cylindrical segment of perineurium removed from the nerve and mounted in vitro on two cannulae was continuously perfused. Permeation rates of 22Na and 42K across the perineurium were the same in either direction and were unaffected by the drugs. The mean 22Na permeability coefficient at the perineurium equaled 1.68 +/- 0.08 (S.E.M.) X 10(-6) cm/sec. Simultaneous measurement of transperineurial fluxes of 22Na, 42K and 36Cl indicated that the K/Na permeability ratio exceeded the ratio of limiting conductances of these ions in free solution, but that the Cl/K permeability ratio did not differ from the respective limiting conductance ratio. Immersion of the perineurial cylinder in Ringer, made hypertonic by addition of NaCl, increased the absolute permeability coefficients of the three ionic tracers but did not affect their permeability ratios. The flux ratio of 22Na/[14C]sucrose, however, was decreased by hypertonic treatment. It is concluded that there is no evidence of active Na or K transport across the perineurium and that the paracellular path in the perineurium exhibits size-dependent permselectivity properties. In addition, the low rates of transperineurial permeation of ions and water-soluble non-electrolytes (e.g. sucrose) are comparable to those in epithelia with tight junctions. These permeability coefficients provide quantitative estimates of the diffusion barrier properties of the perineurium. PMID- 6247017 TI - Calcium reverses the inhibitory action of morphine on neuroeffector transmission in the mouse vas deferens. AB - In the mouse vas deferens, the amplitude of excitatory junction potentials (e.j.p.s.) recorded intracellularly from smooth muscle cells was found to be proportional to stimulus intensity. Normorphine (0.4-2-10 microM) reduced the amplitude of these postsynaptic transients and shifted the stimulus-response curve to the right; i.e. in its presence, higher stimulus intensities were required to elicit an e.j.p. of a similar size to one generated in its absence. Naloxone (0.4 microM) reversed the inhibitory effect of normophine (2 microM). Membrane potentials were unaffected by the concentrations of normorphine employed in solutions of varying ionic compositions. Manoeuvres designed to increase intracellular free calcium, that is increasing the extracellular Ca+ ion concentration (from 2.5 to 5 or 10 mM), removing Mg2+ ions from a medium containing 5 mM Ca2+ or applying 4-aminopyridine (100 microM), enhanced the e.j.p. amplitude and reversed the inhibitory effect of normorphine. Lowering the concentration of Ca2+ ions (from 2.5 to 1 mM) or increasing the concentration of Mg2+ ions (from 1.2 to 4.8 mM) in the bathing solution reduced the amplitude of e.j.p.s. Short trains of impulses (3Hz) facilitated the amplitude of successive e.j.p.s., probably by elevating the intracellular Ca2+ ion concentration. The inhibitory effect of normorphine upon these transients was inversely proportional to the length of the train. It is concluded that the reversal of the effect of normorphine by calcium does not occur at the level of the opiate receptor, and that the opiate depresses the stimulated release of the excitatory transmitter by a reduction in the supply of Ca2+ ions to the stimulus-release coupling mechanism in the sympathetic nerve terminals. PMID- 6247018 TI - Excitatory projections between the midbrain tegmental area and the pontine reticular formation of the rat. PMID- 6247019 TI - Pro-opiocortin fragments in human and rat brain: beta-endorphin and alpha-MSH are the predominant peptides. AB - The 'pro-opiocortin' fragments, beta-lipotropin, beta-endorphin, ACTH and alpha MSH, were estimated in discrete areas of rat and human brain and pituitaries by means of radioimmunoassay in combination with gelfiltration. These peptides exhibited parallel patterns of distribution, but with beta-endorphin and alpha MSH predominant in the brain of rat and man, and, in contrast, their respective precursors. beta-LPH and ACTH predominant in the adenohypophysis of rat and man. These data may be indicative of important differences in post-translational processing of 'pro-opiocortin' between these contrasting tissues. PMID- 6247020 TI - Influence of glutamate and aspartate on time course of decay of excitatory synaptic currents at locust neuromuscular junctions. AB - The influence of glutamate and aspartate on the time course of decay of excitatory currents at neuromuscular junctions of locust skeletal muscle was examined. Both aspartate (up to 10 mM) and glutamate (up to 0.3 mM) had little influence on the decay time of the synaptic currents, whether measured intracellularly by voltage-clamp or extracellularly with a focal electrode. These results do not exclude a role for an active uptake system in sequestering neurally released transmitter at locust neuromuscular junctions, but they suggest that it has a negligible influence on the time course of the synaptic currents. PMID- 6247021 TI - A specific effect of morphine on evoked activity in the rat hippocampal slice. AB - The effect of morphine (0.5-50 microM) was examined on CA1 field potentials in the tranverse hippocampal slice. Morphine consistently produced an augmentation of evoked activity manifest as (i) a decrease in the threshold for generation of a population spike and (ii) generation of an additional population spike(s) whose amplitude was proportional to the position of the sampled response on its input/output curve. Both of these opiate effects were stereospecific and naloxone reversible. Additional population spikes occurred in opiate medium with either orthodromic or antidromic activation of the pyramidal cells, and the antidromic effect was abolished when synaptic transmission was blocked, suggesting that morphine did not act directly upon the pyramidal cells. Recordings of population EPSPs in the dendrites of the pyramidal cells showed no changes due to opiate exposure near threshold. Opiate effects were mimicked by the gamma-aminobutyric acid (GABA) antagonist picrotoxin, and were partially to fully reversed by GABA itself, suggesting that disinhibition of pyramidal cells might be involved as a mechanism in this opiate effect. The data are evidence for a specific primary effect of morphine within the hippocampus in spite of the low numbers of opiate receptors in this brain region. PMID- 6247022 TI - Extracellular potassium in rat cerebellar cortex during acute and chronic lithium application. PMID- 6247023 TI - Hypothalamo-pituitary regulation of hepatic prolactin receptors in the rat. AB - The number of specific binding sites for 125I-labeled human prolactin (hPrl) in crude membrane fractions from rat liver is sexually differentiated. Livers from female rats specifically bound much more of added [125I]hPrl than male liver membrane fractions which bound little, if any, Prl. Hypophysectomy of female animals eliminated hepatic binding of Prl; the effect was reversed by a pituitary implant under the kidney capsule. Treatment of male rats with estradiol valerate induced hepatic hPrl receptors, but only in the presence of an intact pituitary. Anterior hypothalamic deafferentation at the retrochiasmatic level in male rats increased the hepatic hPrl receptor concentration to the female level 3-4 days following the operation. This induction of hPrl receptors was also seen in the absence of the gonads. A transection rostral to the suprachiasmatic nucleus had no effect on the concentration of hPrl receptors in male animals. Our results demonstrate that [125I]hPrl binds specifically to rat liver membranes and that the number of binding sites is regulated by the hypothalamo-pituitary system. The regulatory brain centre appears to be located in the anterior hypothalamus or adjacent areas. The receptor-inducing pituitary factor might possibly be related to the so-called 'feminizing factor' involved in pituitary control of liver enzymes that metabolize drugs and steroids. PMID- 6247024 TI - Distribution of beta-lipotropin (beta-LPH), adrenocorticotropin (ACTH) and alpha melanocyte-stimulating hormone (alpha-MSH) in the rat brain. I. Origin of the extrahypothalamic fibers. PMID- 6247025 TI - Phylogenetic distribution of [3H]kainic acid receptor binding sites in neuronal tissue. AB - The phylogenetic distribution of specific binding sites for kainic acid was determined in 14 species including invertebrates and vertebrates. The highest level of binding was observed in brains of the frog (Xenopus laevis), followed by the spiny dogfish (Heterodontus francisci), the goldfish (Carasius auratus) and the chick (Gallus domesticus). Although significant specific binding was noted in some of the lowest forms tested (e.g. Hydra littoralis), this was not a consistent observation in the invertebrates. In most cases, specific binding to both high and low affinity sites was detected; notable exceptions were the cockroach brain (Periplaneta americana), which had negligible high affinity binding, and the crayfish brain (Procambarus) which had negligible low affinity binding. In the spiny dogfish, the smooth dogfish and the chick, the highest level of binding occurred in cerebellum with less in the forebrain and the least in the medulla; in the mammalian species, the highest level of binding occurred in the forebrain structures with less in the cerebellum and least in the medulla. Eadie plots of the saturation isotherms for [3H]kainic acid revealed similar kinetics of binding for frog whole brain, rat forebrain and human parietal cortex with two apparent populations of binding sites: KD1 = 25--50 nM and KD2 = 3--14 nM. While binding in the spiny dogfish forebrain and human caudate nucleus occurred exclusively at a high affinity component, the cerebella of chick, rat and man exhibited only a low affinity binding site. In the 3 species studied most extensively, frog, rat and man, unlabeled kainic acid was the most potent inhibitor of the specific binding of [3H]-kainic acid. L-Glutamic acid was 20--20 fold less potent than kainic acid, and D-glutamic acid was 4--2500-fold less potent than its L-isomer. Reduction of the isopropylene side chain of kainic acid to form dihydrokainic acid decreased the affinity of the derivative 115--30,000 fold. Hill coefficients derived from these displacement curves were 1.0 for unlabeled kainic acid but approximately 0.5 for L- and D-glutamic acids and dihydrokainic acid, which is compatible with negative cooperativity. In summary, these studies demonstrated a widespread distribution throughout the animal kingdom of specific binding sites for kainic acid in neural tissue; the characteristics of these receptor sites are remarkably similar from primitive vertebrates to man. PMID- 6247026 TI - Inhibitory effect of dibutyryl cyclic GMP on potassium-stimulated 45Ca uptake by synaptosomes from rat brain. AB - The effects of dibutyrl cyclic GMP (db-cGMP) and dibutyryl cyclic AMP (db-cAMP) on potassium-stimulated 45Ca uptake by the P2 fraction of Gray and Whittaker were investigated with the following results. (1) db-cGMP inhibited the initial rate of potassium-stimulated 45Ca-uptake in a dose-dependent manner in 0.1 mM Ca0 medium, but had no effect on the uptake in low K+ medium. In 0.1 mM Ca0 medium, the concentration of db-cGMP causing 50% inhibition was about 3 mM. db-cAMP (5 mM) had no effect on the uptake. (2) db-cGMP-inhibited potassium-stimulated 45Ca uptake in 1 mM Ca0 medium, though less than in 0.1 mM Ca0 medium. (3) db-cGMP inhibited potassium-stimulated 45Ca uptake by synaptosomes (pinched-off nerve terminals) more than the uptakes by other subfractions of P2 fraction. It is suggested from the results that cGMP inhibits the Ca influx resulting from depolarization of the nerve endings in situ. PMID- 6247027 TI - Dopamine released from dendrites in the substantia nigra controls the nigral and striatal release of serotonin. AB - Using push--pull cannulae, the release of endogenously synthesized [3H]serotonin was estimated in both substantia nigra and caudate nuclei of 'encephale isole' cats. The unilateral nigral application of dopamine (10(-7) M) reduced [3H]serotonin release in ipsilateral structures whereas alpha-methylparatyrosine (10(-4) M) induced opposite effects. Both treatments decreased [3H]serotonin release in the contralateral caudate nucleus but not in the contralateral substantia nigra. As a working hypothesis it is suggested that the effects observed are related to changes in the activity of nigroraphe neurons regulated by dopamine release from dendrites of the nigrostriatal dopaminergic neurons. However it cannot yet be excluded that the local changes in [3H]serotonin release induced by the nigral application of dopamine or alpha-methylparatyrosine result from presynaptic modulation. PMID- 6247028 TI - Effects of D,L-alpha-aminoadipate on postsynaptic amino acid responses in cultured mouse spinal cord neurons. AB - The effects of the dicarboxylic amino acid, DL-alpha-aminoadipate (DLAA) on amino acid responses have been investigated using intracellular recordings from mouse spinal cord neurons grown in dissociated cell culture. DL-alpha-Aminoadipate markedly antagonized postsynaptic responses to iontophoretically appllied aspartate; antagonism of glutamate was much less prominent. DL-alpha-Aminoadipate altered the affinity of aspartate for its receptor while having no observed effects on aspartate-receptor cooperativity. No direct effects of DLAA on membrane potentials or passive membrane properties were seen at the currents used for antagonism. Responses to the inhibitory amino acids GABA and glycine were unaffected by DLAA. PMID- 6247029 TI - Bombesin: receptor distribution in brain and effects on nociception and locomotor activity. AB - The radioreceptor assay was used to examine the distribution of bombesin receptors in the rat brain. The highest concentrations of receptors appeared to be associated with limbic forebrain and midbrain structures such as the hippocampus, amygdala, hypothalamus and the periaqueductal gray matter. The caudate-putamen of the extrapyramidal motor system and the forebrain also exhibited high bombesin binding. Intraventricular injections of bombesin (0.1, 1.0 and 10 microgram) produced a dose-dependent increase in locomotor activity in rats. Injections of bombesin into the periaqueductal gray matter produced an antinociceptive reaction in the hot-plate as well as the tail-flick test. This apparent analgesia was not antagonized by naloxone. PMID- 6247030 TI - Strontium supports synaptic transmission and long-lasting potentiation in the hippocampus. AB - (1) Synaptic transmission was studied in isolated transverse hippocampal slices from guinea pigs. Extracellular evoked potentials were recorded in the region CA1. (2) Changing the normal perfusion solution (containing 2 mM Ca2+) to calcium free Ringer abolished synaptic transmission which was again restored by adding strontium. A synaptic efficacy of 25--50% ofn normal was obtained for 10 mM Sr2+. (3) Two different synaptic inputs to CA1 pyramidal cells were tested with respect to their ability to produce long-lasting synaptic potentiation after tetanization in strontium Ringer. Following a brief tetanus the field EPSP and, especially, the population spike were greatly enhanced. (4) The potentiation so produced was similar to the long-lasting potentiation seen in the normal slice, because it (i) had a very long duration (hours), (ii) was specific for the tetanized pathway, (iii) showed potentiation of both 'volley-EPSP' and 'EPSP-spike' relations, and (iv) was accompanied by short-lasting (less than 5 min) generalized depression. PMID- 6247031 TI - Excitatory action of opioid peptides and opiates on cultured hippocampal pyramidal cells. AB - Bath application of low concentrations of opioid peptides and higher concentrations of opiates increased the amplitude and duration of excitatory postsynaptic potentials of pyramidal cells and induced long-lasting depolarization shifts. These actions were reversible and blocked by the opiate antagonist naloxone. Synaptic isolation of the cells by exposure of the cultures to 8 mM Mg2+ not only abolished all spiking and synaptic activity, but also obliterated the peptide effects on pyramidal cells, although these cells were still excited by bath-applied glutamate. The opioid peptides had no detectable effect on resting membrane potential and on the input resistance of the penetrated cells. Experiments in which pyramidal cells were synaptically activated by field stimulation provided direct evidence for a disinhibitory action of the peptides. PMID- 6247032 TI - Differences in synaptic effectiveness at frog neuromuscular junctions: evidence for long-term physiological regulation. PMID- 6247033 TI - Modulation of opiate receptor binding in striatum and amygdala by selective mesencephalic lesions. PMID- 6247034 TI - Thyrotropin-releasing hormone has multiple actions in cortex. AB - The responses to application of TRH were examined on 38 identified neurons in sensory motor cortex of cat. Two pyramidal tract (PT) and 3 nonpyramidal tract (NPT) neurons were directly excited by TRH. Two other NPT neurons were inhibited by TRH. TRH potentiated the excitatory action of ACh on 4 of 12 PT neurons and 1 of 2 unidentified cells. None of these neurons showed a direct effect of TRH. TRH did not potentiate the response to Glu on 12 cells tested, even when the same cell showed TRH modulation of the ACh response. None of the NPT cells examined showed TRH modulation of the excitatory ACh response. These results demonstrate that TRH has multiple actions in mammalian cerebral cortex, but that these actions, such as the modulation of the ACh responses, appear to exist on discrete populations of neurons. PMID- 6247035 TI - Stimulation-induced reduction of large dense core vesicle numbers in cholinergic motor nerve endings. PMID- 6247036 TI - In vivo analysis of GABA receptors on primary afferent terminations in the cat. PMID- 6247037 TI - Long-term decreases in spontaneous firing of caudate neurons induced by amphetamine in cats. PMID- 6247038 TI - Electrogenic pumps in axons and neuroglia and extracellular potassium homeostasis. PMID- 6247039 TI - Recent studies of the actions of cholinomimetic drugs on adrenergic nerves and their implications for the cholinergic link hypothesis. AB - This review analyzes the results of recent studies of the actions of cholinomimetic drugs on adrenergic nerve terminals and their implications for the cholinergic link hypothesis. Thus far, evidence suggests that the only possible action of endogenous acetylcholine (ACh) present near noradrenaline (NA) stores is an inhibition of the release of NA from the adrenergic nerve terminals and that NA is released only when the action of acetylcholinesterase is inhibited. Nicotinic agents have been shown to act on adrenergic nerve terminal membranes, a finding that casts doubt on the proposed intraneuronal cholinergic sites for the action of endogenous ACh. Evidence also indicates that the mode of adrenergic neurone blocking action of bretylium and guanethidine is independent of the proposed cholinergic process in NA release. Current findings do not support the proposal that nicotinic agents in higher concentrations interfere with adrenergic neurotransmission. It is therefore concluded that nicotinic agents, in causing the release of NA from adrenergic nerve terminals, are merely exhibiting a pharmacological action and not mimicking the physiological function of ACh, as proposed by the cholinergic link hypothesis. PMID- 6247040 TI - Interaction of clonidine with chronotropic agents on isolated right atria. AB - Clonidine was administered to isolated guinea pig right atria in order to characterize its chronotropic activity and its interaction with other chronotropic agents at the postjunctional level. Clonidine either had no significant effect (10(-7)--10(-4) M) or decreased (10(-3) M) atrial rate. Pretreatment of the atria with clonidine noncompetitively antagonized (10(-6)- 10(-4) M) the positive chronotropic actions of isoproterenol, and competitively antagonized (10(-4) M) the negative chronotropic actions of pilocarpine. At doses of 10(-6) or 3 X 10(-6) M, clonidine also noncompetitively antagonized the positive chronotropic effects of 4-methylhistamine and glucagon. The results show that clonidine antagonizes both adrenergic and cholinergic influences on atrial rate at the postjunctional level and suggest that the antagonism of adrenergic influences does not involve a direct interaction with beta-adrenergic receptors. PMID- 6247041 TI - The temperature dependence of ionic influences on contractile function in frog twitch muscle. AB - Alterations in the ionic composition of the medium produce striking changes in the potential-dependent contractile responses of skeletal muscles. This study was undertaken to examine the temperature dependence of some of these effects. The suppression of maximal K contractures of frog toe muscles in media lacking divalent cations was largely overcome by a sufficient increase in temperature. The restoration of K contractures by perchlorate in the absence of divalent cations was prevented by a sufficient decrease in temperature. The effect of perchlorate was to shift the temperature dependence of these contractures toward lower temperatures. The reduction in the amplitude of maximal K contractures in the absence of divalent cations was less marked after pretreatment with a reagent (trinitrobenzenesulfonate) that selectively modifies free amino groups, although the temperature dependence of these contractures was unchanged. The reduction in the amplitude of K contractures in the presence of an organic anion (hexanoate) was partially antagonized both by an increase in temperature or by a decrease in temperature, effects that resemble those observed in solutions in which the divalent cation concentration was reduced. In chloride solutions, the relation between [K]0 and K contractures was shifted toward lower [K]0 by an increase in temperature, whereas in perchlorate solutions increased temperature produced a shift in the opposite direction. The shift in this relation toward lower [K]0 at reduced temperature, and the accelerated time course of K contractures with an increase in temperature were similar in perchlorate and in chloride solutions. Thermodynamic analysis by Arrhenius plots indicated that the influence of divalent cations and perchlorate anions on K contractures may be the result of their effects on hydrational factors. PMID- 6247043 TI - Effects of isoproterenol on insulin and glucagon secretion in rats treated chronically with isoproterenol. PMID- 6247042 TI - Interactions between p-tyramine, m-tyramine, or beta-phenylethylamine and dopamine on single neurones in the cortex and caudate nucleus of the rat. AB - p-Tyramine, applied to cortical and caudate neurones with weak iontophoretic currents (0-10 nA), did not usually cause any alteration of base-line firing rate. However, neuronal responses to dopamine (DA) during such weak applications of p-tyramine were greatly enhanced. Cortical neurone responses to noradrenaline (NA) were similarly potentiated, but both cortical and caudate neurone responses to alpha-aminobutyric acid were unaffected by p-tyramine. In addition, weak background applications of DA which did not affect cell firing rate were also without effect on the neuronal responses to the standard application of DA. The responses of cortical neurones to DA were also potentiated by m-tyramine and beta phenylethylamine applied with weak cationic currents. The results may suggest that trace amines can enhance NA and DA transmission in the central nervous system. PMID- 6247044 TI - Effects of phentolamine on hepatic PO2 in endotoxemia. AB - The effect of phentolamine, an alpha-adrenergic blocker, on hepatic oxygen supply, plasma glucose, and lactate, and survival in fasted male rats administered Echerichia coli endotoxin (25 mg/kg, ip) has been studied. Survival at 24 h was 8% in untreated endotoxic rats, 83% in rats receiving phentolamine (5 mg/kg, ip) and endotoxin, and 100% in phentolamine controls. Measurements during the initial 8 h postendotoxin recorded transiently lower systemic arterial pressure in the phentolamine-endotoxic rats. Arterial PO2 and increases of pH and heart rate were similar in both endotoxic groups. Lactacidemia, present by 4 h in untreated endotoxic rats, did not develop in the phentolamine group and plasma glucose was significantly higher at 8 h (98 +/- 2.5 vs. 77 +/- 5.6 mg%, mean +/- SE). Mean hepatic PO2 at 6 h in phentolamine-endotoxic rats was 9.6 mmHg with 28% of the values below 5 mmHg. By contrast, the mean in untreated endotoxic rats was 1.9 mmHg with 88% of values below 5 mmHg. Phentolamine controls were stable over 8 h; mean hepatic PO2 was 17.7 mmHg. The differences in plasma glucose and lactate suggest protection of hepatic metabolism in phentolamine-treated endotoxic rats by prevention of excessive hepatic hypoxia. PMID- 6247045 TI - Ultrastructural analysis of the effect of netropsin on sporulation of Bacillus subtilis. AB - An electron microscopic analysis of Bacillus subtilis cells revealed that netropsin blocked sporulation ultrastructurally at stages 0-I. These observations are consistent with previous results which indicated that cells were not committed to sporulation in the presence of the drug. Further, the addition of netropsin up to stage III of sporulation prevented the normal sharp increase in dihydrodipicolinate synthase activity which results in dipicolinic acid accumulation of stage IV. The addition of netropsin after stage III had much less effect on the synthesis of dihydrodipicolinate synthase and on sporulation. Thus, morphological events in sporulation are blocked early whereas a sporulation associated enzyme may be affected at later stages. These data indicate than netropsin affects the expression of sporulation-associated genes in a differential manner. PMID- 6247046 TI - Polymorphonuclear neutrophil-mediated antibody-dependent cell cytotoxicity of herpesvirus-infected cells: ultrastructural studies. AB - Bovine polymorphonuclear neutrophils (PMN) can mediate antibody-dependent cell cytotoxicity (ADCC) of herpesvirus-infected cells. Since cytotoxicity occurs only in the presence of PMN and specific antiviral antibody, but not until viral membrane antigens are expressed on the target cell, it is concluded that antibody must recognize viral membrane antigens before cytotoxicity can occur. Cytotoxicity also requires very close contact between the target cell and the PMN cell. These interactions occur as early as 1 h after incubating antibody, infected cells, and PMN, but the actual lysis and release of intracellular components occur over an extended period. It was assumed that degranulation was not involved in the initiation of cytotoxicity, but was involved in the final stage of destruction. The mechanism of lysis is proposed to involve the interaction of PMN membranes with target cell membranes with subsequent reorganization and activation of the PMN plasma membrane at points of contact with the target cell. This results in possible production of transmembrane channels which allows for the release of target cell contents. PMID- 6247047 TI - Parasporal crystals produced by oligosporogenous mutans of Bacillus thuringiensis (Spo-Cr+). AB - Six oligosporogenic (Spo-) mutant strains of Bacillus thuringiensis were selected from survivors of treatment with N-methyl-N'-nitro-N-nitrosoguanidine. Each strain was blocked at or before stage II of spore development, but all produced typical bipyramidal-shaped crystalline inclusion bodies. Toxicity of the paraporad typical bipyramidal-shaped crystalline inclusion bodies. Toxicity of the parasporal endotoxin isolated from the mutant strains was assayed by an in vitro technique using cultured insect cells, and was comparable with that of normal wild-type parasporal protein. Multiple parasporal inclusion bodies per cell were often produced, and smaller embedded particles were numerous and distinct. PMID- 6247048 TI - Enteric viruses in renovated water in Manitoba. AB - Using various concentration procedures (including the gauze pad method, ultrafiltration, and adsorption-elution), enteric viruses, mainly vaccine strains of polioviruses, were isolated from 61.8% of sewage, 20.5% of effluents, 3.0% of river water, and 6.7% of drinking water samples collected from a waterway system in Manitoba. The presence of polioviruses in the drinking water of the town utilizing this waterway was not correlated with an increase in the number of infectious diseases reported. PMID- 6247049 TI - Interaction of concanavalin A with herpes simplex virus infected cells. AB - Incubation of herpes simplex virus (HSV) infected cells with concanavalin A (Con A) interferes with binding of the Fc portion of antibody. In addition, the lectin inhibits complement mediated cytolysis, probably by interference with antibody binding. These results suggest that binding sites of both Fc and HSV antibody contain residues which attract Con A. PMID- 6247050 TI - Relation between hepatic lesions and use of oral contraceptives. PMID- 6247051 TI - Liver and the contraceptive pill. AB - Oral contraceptives have been used for many years and a number of adverse effects have been recognized (e.g., jaundice, deep vein thrombosis, thromboembilic disease, gallbladder disease, breast carcinoma, endometrial carcinoma and photosensitivity). Tumour-like lesions of the liver have also been reported. The presentation of such tumours, their management and pathologic features are reviewed. The biochemical effects of the oral contraceptive on the liver, with particular reference to jaundice, are discussed in detail. PMID- 6247052 TI - Linitis plastica of the cecum. AB - Linitis plastica of the cecum is rare. The authors describe a case of this condition in a 16-year-old man. The commonest presenting symptom is a change in bowel habit. Histologically there are three recurring features--diffuse infiltration of the bowel wall by small darkly staining tumour cells, the presence of multiple "signet-ring" cells indicating mucin production and, third, an attempt at gland formation. The prognosis is poor; no patient has survived longer than 27 months. PMID- 6247053 TI - Carcinoma metastatic to the anterior ocular segment: response to chemotherapy. AB - Metastatic carcinoma involving the anterior ocular segment is an exceedingly rare complication of disseminated malignant disease. Non-surgical treatment is ineffective and patients may require enucleation for relief of pain. We describe a response to chemotherapy in a patient having a metastasis from small cell carcinoma of the lung to the iris. By one month following commencement of therapy, complete gross tumor resolution had occurred. PMID- 6247054 TI - Primary mucinous carcinoma of the thyroid gland: report of a case and ultrastructural study. AB - A follicular carcinoma of the thyroid with extensive mucin production was found in a 54-year-old woman. The primary nature of this rare neoplasm of the thyroid gland is supposrted by the presence of both colloid and mucin-producing follicles. Ultrastructural features confirm the secretion of colloid and mucin in the same neoplastic thyroid cells. PMID- 6247055 TI - Non-epithelial tumors of the nasal cavity, paranasal sinuses and nasopharynx: a clinico-pathologic study XI. fibrous histiocytomas. AB - As part of our review of non-epithelial tumors involving the nasal cavity, paranasal sinuses, and nasopharynx, nine fibrous histiocytomas (FH) are reported. FH probably are derived from undifferentiated mesenchymal stem cells that have the ability to differentiate into two different pathways, one fibroblastic and the other histiocytic. The proportion of these two different elements varies greatly in different lesions. The cell population ranges from cytologically benign (small bland nuclei and no mitoses) to overtly malignant (marked anaplasia and numerous mitoses). Based on our cases and on 12 previously reported tumors, FH involving the upper respiratory passages may cause clinical problems similar to those produced by other soft tissue neoplasms affecting this area, (nasal obstruction, a mass or swelling in the involved area, epistaxis, loosening of teeth, or facial pain). Physical examination may show a mass projecting into the nasal, sinus, or oral civity; facial asymmetry; proptosis; or a periorbital mass. Radiographic studies may demonstrate sinus opacification or cloudiness, a mass, or bone destruction. Treatment has included polypectomy, wide local excision, partial maxillectomy, or radical maxillectomy, depending on the size and extent of the lesion. When involving the upper respiratory passages, FH, if incompletely excised, may recur locally, requiring a more extensive resection. A minority of these tumors have metastasized via lymphatic and/or venous channels. Histologic features appear to correlate with clinical course. PMID- 6247056 TI - Pancreatic alpha cell tumors: case report and review of the literature. AB - Twenty-eight cases of alpha cell tumors of the pancreatic islets have been reported. The clinical features include typical skin rash (termed migratory necrolytic erythema) and stomatitis with anemia, abnormal glucose tolerance, and weight loss. The time course of the disease is variable but the clinical syndrome may be present for up to 15 years (median five years) before discovery of the tumor. In 3 patients, cure was achieved by surgical resection, and in 17 patients in whom metastatic sites were evaluable, 16 involved the liver. Six patients have received chemotherapy: 4 with streptozotocin (STZ); 1 with dimethyl triazeno imidazole carboxamide (DTIC); and 2 with 5-fluorouracil. All 4 patients receiving STZ responded to therapy with objective regression of the tumor and in 3 the dermatitis syndrome receded as well. The selectivity of the STZ for beta cells observed in animals is contrasted with the specific antitumor activity of STZ for alpha as well as beta and delta cell tumors in man. PMID- 6247057 TI - Sequential surgery, radiation therapy, and Alkeran in the management of epithelial carcinoma of the ovary. AB - In 1970, a prospective multidisciplinary protocol was initiated for Stages I through III obviously malignant ovarian epithelial carcinomas. The planned sequential therapy included 1) surgery, 2) radiotherapy (2000 rads to whole abdomen, 3000 rad boost to pelvis), 3) chemotherapy (ten cycles of Alkeran), and 4) a "second-look" surgical procedure. Ninety-six patients were enrolled in this program through 1976. Median follow-up of the survivors was greater than 44 months. Adjusted disease-free survival was 90 percent for Stage I, 64 percent for Stages IIB--IIC, and 16 percent for Stage III. Stage III patients with no palpable tumor at time of initiation of radiation therapy had a survival of 37 percent. No Stage III patient with palpable tumor at time of initiation of radiation therapy was cured. Eight percent of patients developed small bowel obstruction requiring surgical intervention. Three percent of all patients died of hematologic causes; of the 30-month-plus survivors, 5 percent (2 of 37) developed acute myelogenous leukemia. Cure and toxicity will be examined in detail and compared with the literature. PMID- 6247058 TI - Lymph node metastases in adenoid cystic carcinoma of the submaxillary gland. AB - The incidence of neck metastases in adenoid cystic carcinoma of the head and neck is considered low and reported incidence range from 0 to 18%. If tumors of the submaxillary gland are considered separately, the incidence of neck metastases reported ranges from 0 to 100%, with a pooled incidence of 34%, significantly higher (P less than 0.001) than that reported for the parotid gland, which ranges from 0 to 21% with a pooled incidence of 10%. It may be suggested that the high incidence of neck metastases in adenoid cystic carcinoma of the submaxillary gland is due, in some cases, to direct extention of the tumor from the gland to the adjacent nodes or from infiltrated surrounding soft tissues rather than by a classic embolic metastasis. In our series of 10 cases, 4 cases showed lymph node metastases. In 3 of these, slides of the radical neck dissection were available for review and showed direct extension of the tumor from surrounding involved soft tissues, although the possibility of embolic metastasis could not be excluded. In the 3 patients with neck metastases at the time of initial diagnosis, distant metastases also developed early in the course of the disease. PMID- 6247059 TI - Elastosis in benign and malignant salivary gland tumors. A histochemical and ultrastructural study. AB - One hundred sixteen cases of various types of salivary gland tumors were examined for the presence of elastic tissue. Almost all the pleomorphic adenomas (97%) and all the malignant pleomorphic adenomas contained elastic tissue in varying amounts. A high percentage (82%) of adenoid cystic carcinomas also contained elastic tissue but the overall quantity was significantly less than in pleomorphic adenomas. All other salivary gland tumors studied, i.e. adenolymphomas, oxyphilic adenomas, mucoepidermoid tumor, and various variants of monomorphic adenomas, were devoid of significant elastic tissue. At the ultrastructural level, the elastic fibers were mainly seen close to neoplastic myoepithelial-like cells, and all stages of elastogenesis were present, ranging from young elastic fibers with a high microfibrilelastin ratio, usually associated with basal-membrane-like material, to mature fibers consisting mainly of an amorphous electron lucent central elastin component. It is postulated that elastic tissue in the salivary gland tumors is produced by the myoepithelial-like tumor cells rather than by tumor stromal induction as has been described in some types of breast carcinomas. PMID- 6247060 TI - Glomangioma of the trachea. AB - A case of a glomus tumor arising in an unusual site, the trachea, is described. The tumor was composed of a mixture of glomus cells and mast cells. At the ultrastructural level, the glomus cells exhibited features of modified smooth muscle cells. PMID- 6247061 TI - Oat cell carcinoma of the esophagus. AB - A case of oat cell carcinoma of the esophagus is reported. The tumor cells were argyrophilic and electron microscopic examination showed that they contained dense-core granules typical of oat cell carcinoma of the lung and other sites. It is concluded that primary oat cell carcinoma of the esophagus is a recognizable entity derived from argyrophil cells in the esophageal mucosa. The existence of rare esophageal carcinomas with both oat cell and squamoid features is noted and their possible histogenesis is discussed. PMID- 6247062 TI - Vaginal bleeding as a presenting symptom of synovial sarcoma. AB - A case is reported of a woman who presented with bleeding from a vaginal extension of a synovial sarcoma. The patient was unaware of the primary tumor in the left thigh and histologically, the tumor resembled a carcinosarcoma. Awareness of the physical and radiologic findings allowed the correct pathologic diagnosis to be made. The manner of presentation of the tumor is believed to be unique. PMID- 6247063 TI - Intracellular adenosine and guanosine 3',5'-cyclic monophosphate concentrations in rat small and large bowel following single and multiple exposures to 1,2 dimethylhydrazine. AB - The adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) levels were determined in the small and large intestinal tissue of rats that had been exposed to single and chronic administration of the colon carcinogen 1,2-dimethylhydrazine (DMH). A single subcutaneous injection of DMH resulted in a decrease in the intracellular concentration of cAMP and increase in cGMP beyond the levels which had been measured in the unexposed intestinal tissue and DMH induced intestinal adenocarcinomas. Recovery to normal concentrations of the cyclic nucleotides occurred within 30 days. Multiple exposures resulted in maintaining reduced levels of cAMP while cGMP was also found to be lowered upon the chronic administration. A possible explanation for these observations is the expansion of the crypt cell population consisting of replicating intestinal cells that occurs upon exposure to the carcinogen. These findings suggest that cyclic nucleotide alterations may represent a characteristic of the precancerous state of intestinal tissue and indicates further studies are warranted to determine whether these changes may serve as a useful marker in a screening program for colon cancer. PMID- 6247064 TI - Selective inhibition of the nephrotoxicity of cis-dichlorodiammineplatinum(II) by WR-2721 without altering its antitumor properties. AB - Injection of 200 mg/kg of body weight of WR-2721 30 minutes before graded doses of cis-dichlorodiammineplatinum(II) (cisplatin) increased the resistance of Fischer 344 rats to cisplatin-induced nephrotoxicity by a factor of 1.7, but did not alter the sensitivity of three different transplanted tumors to cisplatin induced growth delay. As a consequence, it was possible to administer doses of cisplatin which would have been lethal in the absence of WR-2721 injection, resulting in a proportionally greater tumor response. WR-2721 can, therefore, increase the effectiveness of cisplatin therapy through selective protection against the toxic side effects of chemotherapy. PMID- 6247066 TI - [The effect of exercise on plasma levels of cyclic adenosine monophosphate in labile essential hypertension]. PMID- 6247065 TI - Rapid procedures for determination of endo-N-acetyl-alpha-D-galactosaminidase in Clostridium perfringens, and of the substrate specificity of exo-beta-D galactosidases. AB - Culture fluid of Clostridium perfringens hydrolyzed the synthetic, chromogenic substrates beta-Gal-(1 leads to 3)-alpha-GalNAc-1 leads to OPh and beta-Gal-(1 leads to 3)-alpha-GalNAc-1 leads to OC6H4-NO2-o or -p to beta-Gal-(1 leads to 3) GalNAc and the aglycon. Such assays facilitated the characterization and purification of this endo-N-acetyl-alpha-D-galactosaminidase activity. This activity was purified 1200-fold by fractionation with ammonium sulfate and chromatography on columns of Sephadex-G200, DEAE-Sephadex, and hydroxylapatite. The final preparation showed activity over a broad range of pH, with an optimum at 9.0, but less-pure material had two pH optima, 4.0 and 9.0. Another assay method, which employed the synthetic, chromogenic substrates beta-Gal-(1 leads to 3)-beta-GlcNAc-1 leads to OC6H4NO2-p, beta-Gal-(1 leads to 4)-beta GlcNAc-1 leads to OC6H4NO2-p, and beta-Gal-(1 leads to 6)-beta-GlcNAc-1 leads to OC6H4NO2-p, was developed for the rapid identification of the linkage specificity of exo-beta-D galactosidases from any source via a coupled reaction with N-acetyl-beta-D hexosaminidase. PMID- 6247067 TI - [Detection of coronavirus in human cerebrospinal fluid?]. PMID- 6247068 TI - Localization of the src gene product of the Harvey strain of MSV to plasma membrane of transformed cells by electron microscopic immunocytochemistry. AB - Using electron microscopic immunocytochemistry, we have investigated the intracellular location of the src protein (p21) in cells transformed by the Harvey strain of Murine Sarcoma Virus (Ha-MSV). Antibodies to p21 were derived from tumor-bearing rats inoculated with Ha-NRK cells. The distribution of p21 in intracellular sites in MDCK dog cells transformed by Ha-MSV was examined and quantified using a recently developed immunocytochemical technique. More than 95% of p21 was localized to the inner surface of the plasma membrane in these Ha-MSV transformed cells; p21 was not exposed on the outside surface of the plasma membrane. A similar location was observed by immunofluorescence in other Ha-MSV transformed cell lines, including cells derived from rat, mouse and mink. This finding, and the previous demonstration that p60src of avian sarcoma virus is concentrated on the inner surface of the plasma membrane, suggests that the plasma membrane is a major site of action for transforming proteins. PMID- 6247069 TI - Regulation of 40S ribosomal protein S6 phosphorylation in Swiss mouse 3T3 cells. AB - Addition of serum to resting cultures of Swiss mouse 3T3 cells causes an immediate multiple phosphorylation of 40S ribosomal protein S6. After 60 min of stimulation, changing to medium containing no serum led to the net dephosphorylation of S6. During this same period, a second protein, as yet unidentified, became increasingly phosphorylated. Incubation of cells with cycloheximide prior to the addition of serum almost completely blocked the activation of protein synthesis. There was no effect on the serum-induced phosphorylation of S6. If cells were stimulated in the presence of cAMP phosphodiesterase inhibitors theophylline or SQ 20006, both S6 phosphorylation and the activation of protein synthesis were inhibited. Stimulation of cells with serum also led to an immediate drop in total intracellular cAMP levels. This was blocked by prostaglandin E1 (PGE1), which caused a 10 fold increase in total intracellular cyclic AMP. However, PGE1 had no effect on protein synthesis or S6 phosphorylation. PMID- 6247070 TI - Dedifferentiated variants of a rat hepatoma:reversion analysis. PMID- 6247071 TI - Phase variation: genetic analysis of switching mutants. PMID- 6247072 TI - Transformation by subgenomic fragments of Rous sarcoma virus DNA. PMID- 6247073 TI - Virus protein changes and RNA termini alterations evolving during persistent infection. PMID- 6247074 TI - Isolation of a hybrid plasmid with homologous sequences to a transposing element of Drosophila melanogaster. PMID- 6247075 TI - DNA methylation in the human gamma delta beta-globin locus in erythroid and nonerythroid tissues. AB - We have analyzed DNA modification in the human gamma delta beta-globin gene region at 17 cleavage sites of restriction endonucleases which are unable to cleave DNA if 15-methylcytosine is present at certain positions in their respective cleavage sites. Using this criterion, all sites tested in the globin gene region are fully modified in the germ line (sperm) DNA. In somatic tissues, however, methyl groups are absent at specific sites in the globin gene region. In tissues not expressing the genes, these losses range from one of these cleavage sites in lymphocyte DNA to essentially all of these sites in the entire region in placental DNA. In the DNA of tissues expressing the globin genes, the region surrounding and including the genes expressed shows a low level of modification, whereas the neighboring DNA regions have a high level of modification. The data suggest that a low level of DNA methylation may be a necessary, but not a sufficient, condition for gene expression in higher eucaryotes. PMID- 6247076 TI - [The occurrence of cytomegalovirus infection in renal allograft recipients (author's transl)]. PMID- 6247077 TI - [DNA synthesis and antibody formation in spleen cells of the mouse after in vivo immunization by Escherichia coli lipopolysaccharide modified by polymyxin B]. AB - The addition of polymyxin B to Escherichia coli lipopolysaccharide alters some properties of this molecule, when injected to the Mouse. Spleen cells DNA synthesis was inhibited and delayed when the other functions tested: specific antibody synthesis ad immunoglobulin synthesis were unchanged. The possible implications of this dissociation are discussed. PMID- 6247078 TI - [The cerebral cortex regulates immune responses in the mouse]. AB - Ablation of the left cerebral cortex abrogates the production of thymic hormone, reduces the number of spleen T cells and impairs immunization with sheep erythrocytes. In addition, partial decortication inhibits the ability of sodium diethyldithiocarbamate (DTC) to increase the level of circulating thymic hormone, as well as the number of splenic T cells. Therefore, the cerebral cortex would display an important role to maintain body integrity and relations with the external environment, through its effects on the immune system. PMID- 6247079 TI - The relative time course of early changes in mitochondrial function and intracellular pH during hypoxia in the isolated toad ventricle strip. AB - Changes in the intracellular H+ ion concentration (pHi) and in the oxidation reduction state of the respiratory chain were measured spectrophotometrically in the isolated ventricle strip from the toad (Bufo marinus). The relative time course of the delta pHi as indicated by changes in light absorption of the pH dye neutral red, cytochrome c, and peak isometric twitch tension were compared during transient hypoxic episodes. The first detectable change in pH occurred 4.5 minutes after the peak twitch tension began to decrease with the onset of hypoxia. The initial decrease in tension and reduction of cytochrome c occurred at a similar time prior to the change in pHi. On reoxygenation, cytochrome c rapidly became oxidized, and the pHi and tension recovered more slowly. During acidification by increasing superfusate PCO2, pHi and tension decreased together, and cytochrome c did not change significantly. Thus, although changes in pHi do affect mechanical performance, these results show that mechanical dysfunction pursuant to hypoxia is not directly attributable to intracellular acidification. PMID- 6247080 TI - Identification of an angiotensin receptor in rabbit renomedullary interstitial cells in tissue culture. Correlation with prostaglandin biosynthesis. AB - High affinity binding sites of angiotensin II (A II) have been characterized in rabbit renomedullary interstitial cells in tissue culture. Binding was rapid, specific, and saturable. Scatchard analysis of steady state saturation binding data at 22 degrees C indicated a single binding site with an equilibrium dissociation constant of 3.1 mM. The binding inhibition activities of analogues of angiotensin II correlated with their biological potencies: [Sar1, Ala8]A II greater than [des-Asp1]A II greater than greater than 3--8 hexapeptide. The biologically inactive 1--7 heptapeptide failed to displace the labeled angiotensin II from its binding sites. Angiotensin II directly stimulated prostaglandin E2 biosynthesis by the rabbit renomedullary interstitial cells in tissue culture. The concentration of angiotensin II that resulted in half maximal stimulation of prostaglandin E2 biosynthesis (6.5 nM) correlated with the concentration of angiotensin II that resulted in half maximal occupancy of binding sites (3.1 nM). The relative potency of [des-Asp1] A II as a stimulus for prostaglandin E2 biosynthesis was proportional to its relative binding inhibition activity. These findings demonstrate the biological significance of the angiotensin II binding sites in the rabbit renomedullary interstitial cells in tissue culture and suggest that the cells may provide a homogeneous model tissue for the study of the angiotensin receptor. PMID- 6247081 TI - Anti-alprenolol antibodies in the rabbit. A new probe for the study of beta adrenergic receptor interaction. AB - We immunized rabbits with an antigen prepared by covalent linkage of alprenolol, a beta-adrenergic receptor antagonist, to bovine serum albumin. Competitive inhibition of [3H]dihydroalprenolol binding to antisera with a variety of unlabeled ligands revealed broad antibody specificity for beta-adrenergic antagonists and agonists. The antiserum was subjected to affintiy fractionation on hydroxybenzylpindolol-Sepharose 4B. Successive elution with 100 mM Tris HCl, 1M NaCl, 4 M LiBr, and 5 M guanidine yielded fractions with increasing affintiy for hydroxybenzylpindolol. The ligand-binding properties of these affinity fractionated antibodies suggest that certain of these fractions recognize structural aspects of individual beta-adrenergic ligands which are irrelevant to their biological activity, whereas others can be used to distinguish shared functional properties, such as the ethanolamine side chain, within the structural heterogeneity of beta-adrenergic drugs. In particular, elution of hydroxybenzylpindolol-adsorbed antibody with (-)-propranolol allowed identification of an antibody fraction specific for the (-)-stereoisomer. Thus, affinity fractionation of antibodies raised against beta-adrenergic ligands can provide useful analogues for the further study of the recognition properties of the beta-adrenergic receptor. PMID- 6247082 TI - Receptors for insulin and insulin-like molecules. AB - An increasing body of evidence supports the regulation of hormone action by changes in receptor concentration and affinity. Down and up regulation of insulin and somatomedin receptors by changes in hormone concentration explains the alterations in receptor numbers in obesity or diabetes. However, the changes in receptor affinity that have been described have no known mechanism. In most cases, they occur in vivo, but changes can be produced in vitro by ketone bodies and calcium ions. Calcium ions have also been implicated in insulin action, thus strengthening this relationship. Evaluation of the control of receptor affinity must take into account the effects of metabolites such as glucose and minerals, as well as multiple other factors. The relationship between binding and the biological effect of insulin has to be resolved before the full understanding of insulin action can be reached. The controversial areas of insulin receptor research are becoming clearer, but much more information is required before these questions can be resolved. PMID- 6247083 TI - Angiotensin II receptors. Properties and regulation in adrenal glomerulosa cells. PMID- 6247084 TI - Hormonal responses to angiotensin blockade. Comparison between receptor antagonism and converting enzyme inhibition. PMID- 6247085 TI - Opiate receptors and their clinical implications. PMID- 6247086 TI - Enkephalin, endorphin, and the opiate receptor. PMID- 6247087 TI - Characterization of alpha-adrenoceptors in rat and guinea pig tissues using radiolabeled agonists and antagonists. AB - Tritium-labeled preparations of the selective alpha 2-adrenoceptor agonist, clonidine, and the selective alpha 1-adrenoceptor antagonists, prazosin and WB 4101, were examined for their suitability as ligands for receptor assay. In the rat brain, 3H-clonidine bound specifically with high affinity to membrane sites, and drug displacement studies indicated that these were alpha 2-adrenoceptors. The structural requirements for this receptor were defined by examining a range of clonidine analogues. 3H-Clonidine binding to peripheral tissues of the rat was very low, although peripheral tissues from guinea pig exhibited higher binding. Specific 3H-clinidine binding was not reduced after chemical sympathectomy, suggesting that the binding site, although having characteristics of an alpha 2 adrenoceptor, was not located presynaptically. Studies with 3H-WB 4101 in rat cerebral cortex indicated that this ligand bound to an alpha 1-adrenoceptor which was independent of the 3H-clonidine-binding site. 3H-Prazosin was a ligand for alpha 1-adrenoceptors in guinea pig brain and also in membranes from seminal vesicle. However, in the latter tissue, characterization of the binding site was hampered by a high degree of nonspecific binding (50% of total binding). PMID- 6247088 TI - Cardiovascular receptors and calcium. AB - Sarcolemma-rich microsomal fractions were isolated from rabbit ventricular muscle by differential centrifugation and discontinuous sucrose gradient techniques. The fractions were characterized in terms of calcium binding, enzymic activity, gel electrophoresis, and ultrastructure. Racemate verapamil (1 microM) reduced (P less than 0.001) the Ca2+-binding and Ca2+-activated ATPase activity of these fractions; the activity resided in the l-isomer. 14C-Labeled verapamil was found to be bound to carbohydrate residues in the membrane. Pretreatment with trypsin or phospholipase C diminished the 14C-verapamil binding. When added to isolated hearts perfused under conditions of "low flow," verapamil prevented mitochondrial Ca2+ overload. PMID- 6247089 TI - Purinergic receptors in the heart. PMID- 6247090 TI - Central cardiovascular alpha-adrenoceptors. Relation to peripheral receptors. AB - Clonidine and related drugs cause a specific pattern of cardiovascular depression by an agonistic effect on alpha-adrenoceptors within the central nervous system (CNS). For further characterization of the central adrenoceptors, the actions of three substances of the "clonidine-type" derived from two different chemical groups were studied at peripheral vascular sites. Clonidine and two azepin derivatives had very weak vasoconstrictor activity in isolated perfused rat hindquarters. Signs of desensitization were observed when these drugs were administered repeatedly. However, these compounds exerted antagonism against the vasoconstricting effect of noradrenaline. The ranking order of these drugs in their antagonistic potency was the same as with their central cardiovascular depressor potency. In spinal rats, the three compounds raised blood pressure due to their alpha-adrenoceptor stimulation. The ranking order was the same for the pressor potency as for their central cardiovascular depressor potency. It is concluded that in isolated preparations the agonistic activity of clonidine-like substances on postsynaptic alpha-adrenoceptors might not be representative for their CNS effect. PMID- 6247091 TI - Central nervous beta-adrenoceptors and their role in the cardiovascular action of propranolol in rabbits. PMID- 6247092 TI - Biochemical studies of cardiac beta-adrenoceptors, and their clinical significance. PMID- 6247093 TI - Cardiac beta-adrenoceptors and adenylyl cyclase activity in rabbit heart during conditions of altered sympathetic activity. AB - Chronic (2 weeks) guanethidine treatment of rabbits depleted left ventricular noradrenaline and increased sarcolemmal beta-receptor density and protein yield. Total adenylyl cyclase activity was unchanged. Chronic sinoaortic denervation did not affect ventricular catecholamines and only marginally reduced beta-receptor numbers. PMID- 6247094 TI - Cardiovascular adrenergic receptors in experimental hypertension in the rat. PMID- 6247095 TI - Relationship between maximum chronotropic response to isoproterenol in man and generation of cyclic adenosine monophosphate by lymphocytes. AB - The maximum change in heart period caused by bolus doses of isoproterenol was measured in 10 normal subjects. This was linearly related to the amount of cyclic adenosine monophosphate generated from lymphocytes in the same subjects in vitro after incubation with isoproterenol. This high correlation between cardiac and lymphocyte beta-adrenoceptor stimulation suggests that maximum response does not depend on innervation. Other factors, such as cell membrane properties or levels of circulating catecholamines, may be of greater importance. PMID- 6247096 TI - Pharmacological evidence for differences in the beta-adrenoceptor populations influencing atrial rate in guinea pig and cat. AB - The pA2 values of the selective beta-adrenoceptor antagonists, atenolol and alpha methylpropranolol, have been assessed using the selective agonists, norepinephrine and fenoterol, as positive chronotropic agents in atria. In cat atria both beta 1- and beta 2-adrenoceptors influence atrial rate, whereas in guinea pig atria only beta 1-receptors are involved. PMID- 6247097 TI - Differences in the time-course of responses to alpha- and beta-adrenoceptor and of responses to H1- and H2-histamine receptor stimulation. PMID- 6247098 TI - Evidence for a modulatory role of dopamine in sympathetic transmission. PMID- 6247099 TI - Heterogeneity of glucocorticoid receptors. PMID- 6247100 TI - Subclassification of beta-adrenergic receptors in cultured rat cardiac myoblasts and fibroblasts. PMID- 6247101 TI - The dependence of ultrasonic attenuation and backscatter on collagen content in dog and rabbit hearts. PMID- 6247102 TI - Acute and long-term response to an oral converting-enzyme inhibitor, captopril, in congestive heart failure. PMID- 6247103 TI - Continuous-flow enzymatic determination of total serum cholesterol and method standardization with CDC-calibrated pooled sera. AB - We compared Boehringer Mannheim's enzymatic kit for the continuous-flow (AutoAnalyzer II) determination of serum cholesterol with Technicon's N-24a extraction method. Results for patients' samples analyzed by the enzymatic method were higher than those by the comparison method. To evaluate accuracy in the cholesterol determinations, we enrolled the enzymatic method into the Center for Disease Control's (CDC) Lipid Standardization program. We calibrated the method by use of a pooled sera for which cholesterol content was assigned by CDC after analysis by their reference Abell-Kendall procedure. We discuss the difficulties with available calibration material and limitations in the application of some commercial control materials to the enzymatic cholesterol method. The continuous flow variables, Michaelis-Menton constants, percent ester-hydrolase activity, and other factors affecting the performance of the enzyme-linked cholesterol method are evaluated. We believe pooled sera with an assigned value for cholesterol content is the best calibrator material. PMID- 6247104 TI - Antidiuretic hormone immunoactivity in tumour tissue from patients with bronchogenic carcinoma: with and without hyponatraemia. AB - Antidiuretic hormone (ADH) immunoactivity (28--164 pg/mg wet weight) was detected in the tumour tissue of only three out of thirty-two patients with carcinoma of the bronchus. All three patients had small oat-cell tumours and two had persistent hyponatraemia prior to death. Serum sodium was not obtained in the third patient. Serum sodium was normal in the remaining twenty-nine patients with undetectable ADH immunoactivity. PMID- 6247105 TI - Functional significance of idiopathic adrenal calcification in the adult. AB - Two young adults with idiopathic adrenal calcification are described. In one patient the calcification was probably secondary to adrenal haemorrhage in the neonatal period. Neither patient exhibited clinical features suggestive of adrenal cortical insufficiency, and baseline serum cortisol levels were normal. The corticosteroid responses to ACTH administration and to other provocative tests indicated that both glucocorticoid and mineralocorticoid reserve was normal. One patient showed an appropriate epinephrine response to insulin-induced hypoglycaemia. We conclude that even extensive adrenal calcification may be compatible with completely normal adrenal function. Since, however, little is known of the natural history of this condition, lifelong follow-up of such patients is advised. PMID- 6247106 TI - The importance of pituitary tumour size in patients with hyperprolactinaemia in relation to hormonal variables and extrasellar extension of tumour. PMID- 6247107 TI - Coxsackie B virus antibody responses in juvenile-onset diabetes mellitus. AB - A prospective serological study of patients with recently diagnosed juvenile onset diabetes mellitus was carried out to determine neutralizing antibody responses to Coxsackie B viruses. The sera were tested with and without staphylococcal protein A absorption, to selectively ascertain whether specific IgM or IgG antibody predominated. Of eleven patients studied, ten had reciprocal antibody titres of sixteen or greater to at least one serotype. Three patients showed no reduction in titre in at least one serum sample after protein A absorption, suggesting a predominant IgM-specific primary response to a recent infection by a Coxsackie B virus. The findings support the possibility that at least some cases of juvenile-onset diabetes mellitus are closely related to Coxsackie B virus infections. PMID- 6247108 TI - On incubation of long acting thyroid stimulator with human thyroid and adrenal homogenates. AB - In view of the ability of long acting thyroid stimulator (LATS) containing sera and IgG samples to stimulate the adrenal cortex of the mouse, it was decided to study the effect of incubation of LATS containing IgG with human thyroid and adrenal homogenates. Whereas incubation with human thyroid gland abolished (loss greater than 80%) both the thyroid and adrenocortical stimulatory effects of LATS, incubation with human adrenal gland resulted in a minimal loss (20%) of both of these stimulatory activities; the magnitude of this loss was no greater than that attributable to non-specific absorption observed with liver and kidney homogenates by previous workers. It is suggested that a, human and mouse thyroid receptors for TSH/LATS are similar and that adrenocortical receptor for ACTH/LATS are different; and b, the inability of human adrenal homogenates to neutralize LATS explains the absence of hyperadrenocorticism in patients with Graves' disease. PMID- 6247109 TI - The proliferative T cell response to herpes simplex virus (HSV) antigen is restricted by self HLA-D. AB - T cells from sensitized individuals react with a proliferative response to herpes simplex virus antigen (HSV-Ag) in vitro, when antigen is presented together with autologous macrophages (Mo). We here report that this T-Mo co-operation is restricted by self HLA-D/DR molecules of the sensitized T cell donor. Furthermore, it is shown that the lack of co-operation between T cells and HLA D/DR disparate macrophages, is due neither to suppression nor to generation of cytotoxic T cells in the allogeneic mixture. PMID- 6247111 TI - The lack of beta-adrenoceptor involvement in the cardiac action of delta 1 tetrahydrocannabinol in rats. AB - 1. Rat isolated hearts perfused with delta 1-THC (0.5 micrograms/ml) showed a reduction in the rate of beating which was not altered by pretreatment with propranolol (2 micrograms/ml), atropine (4 micrograms/ml) or hexamethonium (4 micrograms/ml). 2. Propranolol (2 micrograms/ml) also caused a decrease in the rate of beating, which was not affected by pretreatment with delta 1-THC (0.5 micrograms/ml). 3. In pithed rats, propranolol (2 mg/kg, i.v.) caused a decrease in the pulse rate, which was not altered by prior administration of delta 1-THC (1mg/kg, i.v.). 4. In both preparations, the responses to isoprenaline were markedly reduced or abolished by propranolol, but they were unaffected by delta 1 THC. 5. It is concluded that the hypotensive and cardiac slowing actions of delta 1-THC are not mediated by activation of parasympathetic nerves or by beta adrenoceptor blockade. PMID- 6247110 TI - Study on the nature of the Goodpasture antigen using a basement membrane producing mouse tumour. AB - Autoantibodies in the sera of patients with Goodpasture's syndrome showed a strong reaction in indirect immunofluorescence tests on unfixed, frozen sections of a mouse tumour (EHS sarcoma), previously shown to produce extracellular basement membrane. Anti-basement membrane antibodies from patients with bullous pemphigoid failed to react with the mouse tumour, but showed a distinct reaction with cylindroma tissue. Absorption of Goodpasture sera with tumour homogenate completely abolished their reaction on sections of human and murine kidney. Basement membrane (type IV) collagen and a high molecular weight, non-collagenous glycoprotein were isolated from the tumour matrix and studied in absorption experiments and radioimmunoassays. Little or not reaction was observed with Goodpasture patients' sera indicating that neither of these two proteins is the major antigen involved in the disease. Antigenic material reacting with Goodpasture sera was extracted from the tumour in neutral salt solutions, suggesting that it is a non-collagenous protein. PMID- 6247112 TI - The circadian rhythm of thymosin therapy during acute reovirus type 3 infection of neonatal mice. PMID- 6247113 TI - [A case of hypophosphatemia induced by intravenous hyperalimentation and antacids presenting neurological signs and symptoms. A review of the literature (author's transl)]. PMID- 6247114 TI - Pinhold imaging: utility in testicular imaging in children. AB - Pinhole imaging of the testis was done in ten boys with suspected testicular torsion. In three of the ten cases, pinhold images were easier to interpret than images obtained with a converging collimator. In six of the ten cases, pinhold images were required for interpretation of the study, because converging images could not be interpreted. PMID- 6247115 TI - Small cell carcinoma of the lung: primary site and hepatic metastases both detected on Tc-99m-pyrophosphate bone scan. AB - A case of small cell anaplastic carcinoma of the lung with hepatic secondaries has been found to accumulate Tc-99m-pyrophosphate in both lung primary and hepatic metastases and to our knowledge is the first such case reported in the literature. There was no radiographic evidence of calcification in the tumor or hepatic metastases. PMID- 6247116 TI - Age and beta adrenoceptor-mediated function. AB - Beta adrenoceptor-mediated responsiveness to isoproterenol was compared in young and old subjects using the production of cyclic adenosine monophosphate (cyclic AMP) by lymphocytes as an index. The mean log dose-response curve for the elderly group was displaced to the right and the mean maximum response was less than that for the young subjects. The results corroborate evidence of a decreased response to isoproterenol-induced increases in heart rate in the elderly and raise the possibility of a generalized decrease in beta adrenoceptor-mediated functions in old age. PMID- 6247117 TI - [Pharmacological basis for the therapeutic use of calcium inhibitors. Part 1]. PMID- 6247118 TI - Hypoglycemia: test strategies for laboratory evaluation. PMID- 6247119 TI - Foodborne disease outbreaks in Connecticut during 1977 and 1978. PMID- 6247120 TI - Bovine papular stomatitis, first report of the disease in Mexico. AB - In a herd of 120 two to eight months old calves kept at a Mexican Government experimental station in Ajuchitlan, Queretaro, weight loss and ptialism were observed. Upon a clinical examination, it was found that 31 (25.8%) of the animals disclosed papules in the oral and perioral regions. Biopsies from the affected tissues were studied with the light and electron microscopes. Serological studies and isolation of the virus were also carried out. A Pox virus was identified (240 x 100 x 150 +/- 7% nm) with the electron microscope. Dermatophilus sp. was occasionally observed. Bovine kidney monolayers, inoculated with affected bovine tissues demonstrated cytopathic effect up to the 4th serial passage. Inoculation with cell cultured infectious material in the oral submucosa (cell lysate) produced typical lesions of BPS on a heifer. Infectious tissues from this experimentally inoculated animal produced cytopathic effect in tissue cultured cells after 24 hours, and this last material was infectious for a second young heifer. Virus-neutralization tests, using an hyperimmune serum, disclosed a neutralization index of 1.5 logarithms. It was concluded that bovine papular stomatitis virus was the etiological agent. PMID- 6247121 TI - Evaluation of the rabbit as a laboratory model for infectious bovine rhinotracheitis virus infection. AB - Experimental infection of rabbits with infectious bovine rhinotracheitis virus (IBRV) produced diverse manifestations of disease which included abortion, conjunctivitis, dermatitis, vulvovaginitis, systemic infection, neonatal death and respiratory tract infection. Each disease syndrome was studied using virus isolation, fluorescent antibody examination and histologic examination. Conjunctivitis, dermatitis and vulvovaginitis lesions were characterized by edema, infiltration of mucosa and submucosa with inflammatory cells and ulceration of epithelium. Systemic infection resulted in severe necrosis of liver and adrenal glands with large numbers of cells containing intranuclear inculsions. Pregnant rabbits aborted within 48 hours following inoculation of IBRV. Virus infection and viral lesions were not demonstrated in aborted fetuses. PMID- 6247122 TI - Klippel-Trenaunay-Weber syndrome. A case occurring in the ear and associated with arteriovenous fistulas. AB - A case of Klippel-Trenaunay-Weber syndrome is presented herein. Of particular interest were the location in the ear and the association with arteriovenous fistulas. PMID- 6247123 TI - The sequence organization of bovine DNA. AB - The organization of repetitive DNA sequences has been investigated in bovine DNA. Repetitive sequences of all kinds constitute 25% to 30% of the total. Five density satellites constitute about 20% of the genome, and most of the remainder consists of alternating repeating and nonrepeating sequences. The nonrepeating sequences have a very broad size distribution averaging 4,000 nucleotide paris in length with the longest exceeding 10,000 nucleotide pairs. The interspersed repetitive sequences are much more nearly homogeneous in size, averaging 350 nucleotide pairs in length, and are divided into 8 to 14 sequence families. PMID- 6247125 TI - The significance of the signet-cell variety of adenocarcinoma of the rectum. AB - Seventeen cases of signet-cell mucinous adenocarcinoma of the rectosigmoid and rectum, seen over a 25-year period at Memorial Sloan-Kettering Hospital, were reviewed. We conclude, in agreement with previous authors, that it is an infrequent lesion that is usually discovered at an advanced stage. However, with early radical surgical intervention the prognosis can be favorable. PMID- 6247124 TI - Restriction endonuclease and molecular analyses of three rat genomes with special reference to chromosome rearrangement and speciation problems. AB - When differences are found between related species of organisms, it is often assumed that the differences themselves are causal factors either in speciation itself or in processes related to speciation. Two recent proposals on the functions of satellite DNA (Hatch et al., 1976 and Fry and Salser 1977) are that (a) large amounts of satellite DNA are important in facilitating chromosome rearrangements and hence cytogenetic evolution, and (b) satellite DNA differences between homologous chromosomes lead to pairing difficulties and are important in generating infertility barriers and hence speciation. If these proposals were to have some generality, one could expect organisms with very low amounts of highly repeated DNA to exhibit few chromosome rearrangements and to be evolutionarily conservative in a cytogenetic sense.--We have chosen two very closely related species of rat which are phenotypically almost indistinguishable and which have undergone massive genome reorganization. They differ by 11 major centric rearrangements (2n = 32, 2n = 50). We have characterised their genomes by restriction endonuclease digestions, thermal denaturations, analytical ultracentrifugations and reassociation techniques, and have found that they have virtually no highly repeated DNA. Thus the 11 major chromosomal rearrangements have been fixed in present day genomes with hardly any highly repeated DNA, centric or otherwise.--It appears therefore, that a large amount of highly repeated DNA is not obligatory for the formation and fixation of chromosome rearrangements. In addition, the existing literature reveals that one can find almost any situation at all, from species groups with high amounts of satellite DNA and no gross chromosomal rearrangements, to ones such as those described here, with tiny amounts of highly repeated DNA and massive chromosomal reorganisation. Since direct experimental data indicates that satellite DNA differences per se between homologous chromosomes do not cause infertility, speculations concerning modes of speciation based on satellite DNA differences between otherwise homologous chromosomes would appear to be ill founded. PMID- 6247126 TI - Primary malignant fibrous histiocytoma of the intestine: intussusception of a rare neoplasm. AB - Malignant fibrous histiocytoma, a tumor of mesenchymal tissue, is being reported with increased frequency. However, no cases of primary tumors involving the gastrointestinal tract have yet been described. This report documents a case in which the patient clinically manifested a colonic obstruction associated with intussusception. Following radical resection of the mass, close re-evaluation after one year has shown no evidence of tumor recurrence. PMID- 6247127 TI - ["Slow" sodium channels in the somatic membranes of spinal ganglia neurons of newborn rats]. PMID- 6247128 TI - [Spectral analysis of fluctuations in calcium channel conductivity in nerve cell membranes]. PMID- 6247129 TI - [Inactivation of sodium permeability of a nerve fiber membrane by means of formamide]. PMID- 6247130 TI - [CFUs proliferative responses to exogenous soluble and immobilized cyclic nucleotides]. PMID- 6247131 TI - [Mathematic model of inert gas exchange between blood and tissues containing gas bubbles]. PMID- 6247132 TI - [Intermediate DNA structures formed during the course of recombination following conjugation of Escherichia coli K-12]. PMID- 6247133 TI - Effect of 3,5,3'-triiodothyronine and 3,3',5'-triiodothyronine administration on serum tri-, di-, and monoiodothyronines and plasma cyclic nucleotides in sheep. PMID- 6247134 TI - Demonstration of glucocorticoid receptors in the adrenal cortex: evidence for a direct dexamethasone suppressive effect on the rat adrenal gland. AB - The adrenal cortex was evaluated for the presence of glucocorticoid receptors and functions. Substantial binding of [3H]dexamethasone was observed in aminoglutethimide-treated, hypophysectomized, and intact rats. Further studies demonstrated binding in cultured bovine adrenocortical cells and in Y-1 cells, a cloned murine cell line of adrenal cortical origin. Scatchard analysis of specific binding data in cytosol from hypophysectomized rats revealed an apparent Kd of approximately 15 nM and a receptor content (Nmax) of 123 fmol/mg cytosol protein. Analysis of Y-1 cell cytosol showed a Kd of approximately 17 nM and Nmax of 190 fmol/mg protein. The binding site in hypophysectomized rats had the following steroid specificities: high affinity for dexamethasone, corticosterone, and progesterone; moderate affinity for 11 beta-cortisol, and low affinity for testosterone, estradiol, pregnenolone, and 11 alpha-cortisol. Sedimentation in sucrose density gradients revealed 8S binding peaks in cytosols prepared from intact rat adrenal glands, Y-1 cells, and cultured bovine adrenocortical cells. Time- and temperature-dependent nuclear uptake of [3H]dexamethasone in Y-1 cells was demonstrated. In vivo treatment of hypophysectomized rats with dexamethasone significantly enhanced the rate of adrenal atrophy. ACTH stimulation tests in hypophysectomized rats showed a decreased corticosterone response in dexamethasone-treated rats compared to that in control animals. However, in vitro, there was no evidence for an effect of dexamethasone on ACTH-stimulated corticosterone production. The data indicate that the adrenal cortex possesses a high affinity binding site that fulfills the criteria for a glucocorticoid receptor. Glucocorticoid administration enhances adrenal atrophy and impairs adrenal function. We speculate that this action contributes to the suppressive effect of glucocorticoids on the pituitary-adrenal axis. PMID- 6247135 TI - Lack of effect of the vitamin D status on the concentration of the vitamin D binding protein in rat serum. AB - The influence of the vitamin D status on the concentration of the serum vitamin D binding protein was studied. In normal rats the serum vitamin D-binding protein increases gradually from birth to adulthood; after puberty a higher concentration is found in male rats than in female rats. Rats fed a vitamin D-deficient diet containing a sufficient amount of calcium and phosphorus were found to have a normal DBP (binding protein for vitamin D and its hydroxylated metabolites) pattern indistinguishable from that of rats receiving the same diet but supplemented with a weekly injection of 500 microgram vitamin D3. Rats fed a vitamin D-deficient, low calcium, low phosphorus diet developed severe hypocalcemia and growth retardation, but their DBP pattern was not significantly different from that of rats fed the same diet but supplemented with a weekly injection of 500 microgram vitamin D3. The concentration of the transport protein for vitamin D was thus unrelated to the vitamin D status of the rat. PMID- 6247136 TI - Regulation of hamster adrenal 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. AB - In the adrenal gland of the hamster, the activity of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase [mevalonate:NADP+ oxidoreductase (acylating CoA); EC 1.1.1.34] is mainly located in the postmitochondria fraction. This enzyme exhibits a diurnal rhythm, with a maximum at 1900 h. Peak activity levels are about 1667 pmol/mg protein . min, roughly 8 times the minimum levels. Plasma corticosteroid concentrations closely parallel reductase activity levels. The administration of ACTH or metyrapone (a drug which increases in vivo ACTH secretion) to hamsters enhanced the adrenal reductase activity, whereas aminoglutethimide, an inhibitor of the side chain cleavage of cholesterol, diminished it. The feeding of a 5% cholesterol diet and treatment with 4 aminopyrazolopyrimidine resulted in an increase and a decrease in plasma cholesterol, respectively. Neither treatment significantly altered adrenal 3 hydroxy-3-methylglutaryl coenzyme A reductase activity or the cholesterol content of the gland. Hamster adrenals contain very little free cholesterol (7-11 microgram/mg protein) and even less esterified cholesterol (0.5-2.0 microgram/mg protein). These findings suggest that in the hamster the adrenal gland may be largely autonomous in cholesterol production. PMID- 6247137 TI - Constant estrus: role of rostral hypothalamic monoamines in development of reproductive dysfunction in aging rats. PMID- 6247138 TI - Gonadotropin-induced desensitization of epinephrine action in the luteinized rat ovary. PMID- 6247139 TI - Experimental diabetes in the rat causes an insulin-reversible decrease in renal 25-hydroxyvitamin D3-1 alpha-hydroxylase activity. PMID- 6247140 TI - Comparative therapeutic effects of vitamin D3 and its derivatives on experimental renal osteodystrophy. AB - The comparative effectiveness of vitamin D3 and its derivatives in curing hyperparathyroidism and osteodystrophic bone lesions was examined in a laboratory model of renal osteodystrophy associated with marked secondary hyperparathyroidism in rats. The experimental model was prepared by a single injection of homologous glycopeptide. Plasma levels of 1 alpha,25 dihydroxyvitamin D3 [1 alpha,25(OH)2D3] appeared to decrease in the rats receiving glycopeptide. Various doses of vitamin D3 derivatives [2 or 10 microgram/kg D3, 2 microgram/kg 25-hydroxyvitamin D3 (25OHD3), 0.1 microgram/kg 1 alpha,25(OH)2D3, and 0.1 or 0.2 microgram/kg 1 alpha-hydroxyvitamin D3 (1 alpha OHD3)] were daily administered orally to the nephritic rats for 23 days before sacrifice. 1 alpha,25(OH)2D3 and 1 alpha OHD3 were much more potent than 25OHD3 and D3 in reducing the hyperplasia of parathyroir glands. The potency of 1 alpha OHD3 in curing the histological changes of osteodystrophy appeared to be greater than that of 1 alpha,25(OH)2D3. The same dose level of 1 alpha OHD3 was more effective than 1 alpha,25(OH)2D3 in enhancing plasma 1 alpha,25(OH)2D3 levels. PMID- 6247141 TI - Growth factor- and cyclic nucleotide-induced proliferation of normal and malignant mammary epithelial cells in primary culture. AB - Sustained growth of normal mouse mammary epithelial cells in primary culture, leading to an increase in cell number, in response to growth factors [epidermal growth factor (EGF) and fibroblast growth factor (FGF)] or cholera toxin has been achieved by embedding the cells inside collagen cells. Inclusion of agents known to increase the level of cellular cAMP have been found to be favorable for mammary epithelial cell proliferation. Cholera toxin is by far the best of all of the agents tested (prostaglandins E1 and E2, isoproterenol, theophylline, and dibutyryl cAMP). When growth factors (EGF or FGF) are added with cholera toxin, a synergistic effect resulting in a response much greater than with either of them alone is seen. This synergism was best seen in normal mammary epithelial cells from nonpregnant mice. The extent of this synergistic effect was found to be less in normal cells from pregnant mice, suggesting that these cells may be less responsive to EGF during pregnancy. Tumor cells were found to be rather inconsistent in their responses to EGF and cholera toxin, ranging from a minimal response, similar to that of normal cells from pregnant animals, to a maximal response, similar to that of normal cells from nonpregnant animals. PMID- 6247142 TI - Factors determining the diurnal variation in progesterone-induced gonadotropin release in the ovariectomized rat. PMID- 6247143 TI - Divergent effects of prolactin upon steroidogenesis by porcine granulosa cells in vitro: influence of cytodifferentiation. PMID- 6247144 TI - Regulatory actions of angiotensin II on receptors and steroidogenic enzymes in adrenal glomerulosa cells. PMID- 6247145 TI - Thyroxine-induced changes in characteristics and activities of beta-adrenergic receptors and adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate systems in the heart may be related to reputed catecholamine supersensitivity in hyperthyroidism. AB - Modifications in characteristics and activities of beta-adrenergic receptors and certain parameters of the cyclic nucleotide systems were observed in the hypertrophied heart of the rat chronically treated with T4. These include: 1) an increased number of beta-adrenergic receptors without a change in their affinity, as determined by binding of (-)-[3H]dihydroalprenolol to the membrane; 2) increased sensitivity and magnitude of stimulation of adenylate cyclase in homogenates by isoproterenol, without a change in the basal or NaF-stimulated (total) enzyme activity; 3) decreased formation of cAMP and decreased activation of cAMP-dependent protein kinase in the minced heart stimulated by isoproterenol, probably due to decreased myocardial ATP concentration; 4) decreased activity of cAMP phosphodiesterase in the particulate fraction; 5) decreased activity of cGMP dependent protein kinase in both the soluble and particulate fractions, accompanied by decreased activity of cAMP-dependent protein kinase in the particulate fraction; 6) decreased activity of the stimulatory modulator of cGMP dependent protein kinase and, conversely, increased activity of the inhibitory modulator of cAMP-dependent protein kinase; and 7) increased sensitivity accompanied by decreased maximum tension development of the ventricular strip to contract in response to isoproterenol. These alterations largely disappeared upon regression of the hyperthyroid state. It is suggested that the above changes, many of which were the opposite of those reported earlier for the desensitized and hypertrophied rat heart caused by isoproterenol, may in part consitute the molecular basis for the reputed catecholamine supersensitivity of the heart in the hyperthyroid state. PMID- 6247146 TI - Binding of thyroid hormones in serum and liver cytosol of Rana catesbeiana tadpoles. AB - Binding of thyroid hormones to proteins in tadpole serum and liver cytosol was studied using both equilibrium dialysis and dextran-coated charcoal techniques to separate bound and free hormone. Measured directly by equilibrium dialysis, approximately 1% of the total T3 or T4 in serum and less than 0.5% of the total T3 and T4 in cytosol (diluted 1:5 or 1:10) were in the free form. Free T3 and T4 fractions were independent of hormone concentration between 10(-10) and 10(-6) M. Values for free hormone fractions determined by the charcoal-binding technique were much higher than those determined directly, and it was evident that this technique could not be used to measure free hormone fractions if any of the protein-hormone complexes dissociated very rapidly. Nevertheless, important information was obtained using the charcoal technique. It was found that both cytosol and serum contain a number of sets of sites that bind thyroid hormone, some of which are saturable. However, the affinity of the saturable sites for both T4 and T3 is relatively low. The presence of alternative binding sites for excess hormone prevented any increase in the free fraction at high hormone concentrations. No evidence was obtained in either cytosol or serum of any high affinity, low capacity binding sites similar to those detected in tadpole liver nuclei. It is suggested that the binding of thyroid hormones in serum and liver cytosol in tadpoles serves a function other than the initiation of thyroid hormone action. PMID- 6247148 TI - Histologic evidence of cytomegalovirus in the duodenal and gastric mucosa of patients with renal allograft. AB - Endoscopic examination of the upper gastrointestinal tract was performed in 12 patients after renal transplantation and immunosuppressive therapy. Histological examination of the specimens obtained from the duodenal bulb revealed the presence of cytomegalovirus (CMV)-type cells in four cases. In one of these patients several CMV-type cells were scattered in the duodenal mucosa and also affected the antral mucosa. In the other three cases just one or two cells with prominent intranuclear inclusions (CMV) were present in only a few of the multiple sections. No correlation of CMV inclusion with symptoms and with the morphological appearance of the upper gastrointestinal tract has been found. CMV infection seems to be correlated with immunosuppressive therapy. PMID- 6247147 TI - Secretion of epidermal growth factor, nerve growth factor, and renin-like enzymes by dispersed male mouse submandibular gland cells in vitro. PMID- 6247149 TI - Neuronal activity in chronic ferric chloride epileptic foci in cats and monkey. AB - The firing patterns of neurons surrounding sites of ferric chloride (FeCl3) injection were studied in 6 cats and 1 Macaca mulatta monkey. Although a few neurons fired in poorly structured bursts similar to what has been described for some neurons in alumina foci in monkeys, no well-formed bursts were recorded. In addition, EEG spikes were not recorded chronically in two cats, nor were EEG spikes recorded during corticography. We could not confirm the reliability of this preparation in cats as a model of chronic epilepsy. PMID- 6247150 TI - The nature of the inhibition of cholesterol esterase by delta 1 tetrahydrocannabinol. AB - An improved assay for cholesterol esterase based on the use of fatty acid radiolabelled cholesterol esters has been developed. The method was used to demonstrate the effects of delta 1-tetrahydrocannabinol on a crude Leydig cell esterase preparation and on crystalline pancreatic esterase. Both enzymes were inhibited and the Km values determined (6.6 mumol/1 for the Leydig cell esterase and 6.25 mumol/1 for the pancreatic enzyme). While the former exhibited a mixed type of inhibition, the latter clearly was competitive. PMID- 6247151 TI - On the mechanism of the cytochrome c oxidase reaction. Bound Fe(III) cytochrome c as an intermediate in the reductive half reaction. PMID- 6247152 TI - Alterations in enzymes related to adenosine 3',5'-monophosphate during compensatory growth of rat lung. AB - Left pneumonectomy in rats induced growth of the right lung which was maximum one week after the operation. This compensatory lung growth was accompanied by an increase in adenylate cyclase/cyclic AMP phosphodiesterase activity suggesting an increase in the lung adenosine 3',5'-monophosphate (cyclic AMP) levels after pneumonectomy. Activities of cyclic-AMP-dependent protein kinase, phosphorylase and glucose 6-phosphatase were also increased suggesting the enhanced activity of the cascade system (glycogenolysis). Activities of these enzymes were maximally elevated during the first three days of operation and preceded the growth of contralateral lung, returning to the presurgery level on day 14. These data indicate that: (a) the biochemical response to pneumonectomy in rats appeared to be complete in two weeks and, (b) changes in the activities of cyclic-AMP-related enzymes may be important in the compensatory growth of rat lung. PMID- 6247153 TI - Degradation of basement-membrane collagen by neutral proteases from human leukocytes. AB - A neutral extract from human leukocytes was shown to have proteolytic activity which could degrade triple-helical basement membrane collagen from bovine lens capsules into specific triple-helical sub-fragments. The enzymes responsible is not identical to the leukocyte collagenase active against interstitial collagen types I, II and III. After denaturation, the neutral protease reaction products showed three major peptides with molecular weights of 70,000, 50,000 and 30,000, by dodecylsulphate gel electrophoresis analysis. Electron microscopic observation and viscosity measurements showed the initial twice-pepsinized collagen to be comprised of intact rod-like molecules about 300 nm long. The fragments produced by the protease were also triple-helical and were resistant to the action of trypsin at 20 degrees C. The fragments were completely degraded by purified bacterial collagenase or by raising the reaction temperature above the melting temperature of the basement membrane collagen during incubation with leukocyte extract. Enzyme activity has its pH optimum between 7 and 9, EDTA, EGTA and 1,10 phenanthroline (metal-chelating agents) completely inhibited enzyme activity, as did serum. Partial inhibition of the activity was obtained with phenylmethylsulfonyl fluoride and soybean trypsin inhibitor. PMID- 6247154 TI - Effect of ATPase inhibitors on the proton pump of respiratory-deficient yeast. AB - Diethylstilbestrol and dicyclohexylcarbodiimide inhibit the ATPase of the plasma membranes and the proton-pumping activity of the cells in a respiratory-deficient mutant of Saccharomyces cerevisiae. The effects of the inhibitors in vivo seem to be specific because neither the proton permeability nor the ATPase levels of the cells are affected. These results indicate that the yeast plasma-membrane ATPase corresponds to the proton pump of the cells. The fact that both inhibitors of the ATPase delay the fall of ATP levels which follows a block of fermentation indicates that ATPase function is one of the major ATP-consuming pathways in yeast. In addition, diethylstilbestrol prevents the fall of ATP levels produced by dinitrophenol, suggesting that this fall was caused by partial dissipation of the proton gradient and consequent stimulation of the proton-pumping ATPase. PMID- 6247156 TI - Lymph node visualisation: an unusual artefact in the 99mTc-pyrophosphate bone scan. AB - Extraskeletal uptake of tracer, presumably in the lymph nodes, is an uncommon finding in bone scans. It has been seen only when there is extravasation of tracer at the injection site. The phenomenon appears to be the result of colloid formation. PMID- 6247155 TI - Clinical evaluation of 201thallium chloride scan for thyroid nodule. AB - Thyroid scintigraphy with Tl in the evaluation of nodules was investigated. A Tl scan was performed on 55 patients with thyroid nodules previously scanned with Tc or I. In the case of 16 carcinomas, accumulation of Tl was shown in every case. In addition, some lymph node metastases were depicted. (Accumulation was noted also in some of the metastatic lymph nodes.) Cold defect was delineated in ten cases of colloid and fetal adenoma, although accumulation was shown in four cases of Hurthle and embryonal adenoma. Six cases of degenerative cysts were delineated as cold defect. As for colloid nodular goiter, the affinity to the individual nodule was not constant. In general, degenerative and cystic nodules showed less activity and hyperplastic solid nodules showed more activity than normal tissue. We concluded that although a Tl scan cannot differentiate between benign and malignant tumors satisfactorily, it is nevertheless useful for determining surgical indication, as the case showing Tl accumulation on the scan is malignant or benign tumor with poorly differentiated solid type and possiblility of further growth and malignant change. PMID- 6247157 TI - Subclassification of two types of alpha-adrenergic binding sites in rat liver. AB - Drug specificity studies with prazosin and yohimbine indicated that the two types of alpha-adrenergic binding sites identified using [3H]-epinephrine and [3H] dihydroergocryptine in rat liver plasma membranes both belong to the alpha 1 sublcass. PMID- 6247158 TI - Influence of haloperidol on ACTH and beta-endorphin secretion in the rat. AB - The injection of haloperidol, a dopamine receptor blocker, was followed by a large increase of plasma ACTH and beta-endorphin-like immunoreactivity (beta-EI) in the rat. This effect was prevented when the rats were previously treated with corticosteroids. These results suggest that catecholamines inhibit ACTH and beta endorphin secretion in the rat. PMID- 6247159 TI - Comparison in mice of pharmacological effects of delta 8-tetrahydrocannabinol and its metabolites oxidized at 11-position. PMID- 6247160 TI - Structure-activity relationships of enkephalin analogs at opiate and enkephalin receptors: correlation with analgesia. AB - We have investigated the influence of physico-chemical parameters (chemical structure and lipophilicity), biochemical properties (catabolism, affinity for 3H etorphine binding sites and 3H-(D-Ala)2-Leu5-enkephalin amide binding sites) and biological activity in isolated organs (guinea-pig ileum and mouse vas deferens) on the regulation of analgesia induced after intracerebroventricular injection of various enkephalin analogs. The selectivity of these metabolically stable analogs for micro- and beta-receptors, present in guinea-pig ileum and mouse vas deferens respectively, depends on the C-terminal amino acid and also on the nature of the second D-amino-acid. A strong correlation exists between activity in guinea-pig ileum and affinity for 3H-etorphine binding sites suggesting that these sites in rat brain have properties identical to those of micro-receptors characterized in guinea-pig ileum. Similarly, the affinity for 3H-(D-Ala)2-Leu5-enkephalin amide binding sites in mouse brain is correlated to the activity in mouse vas deferens and suggests that central beta-receptors are not different from peripheral beta receptors. If we consider morphine-like drugs and enkephalin analogs containing the same C-terminal amino acid as the enkephalins, there is a good correlation between activity on micro-receptors (affinity for 3H-etorphine binding sites and activity in guinea-pig ileum) and the antinociceptive activity. These results support the hypothesis that micro-receptors are strongly involved in the analgesic effect. However, when proline is the C-terminal amino acid, the antinociceptive activity was enhanced without any concomitant increase in the affinity. This activity enhancement was the same for each analog and a similar correlation (identical to what was found with other opioid peptides and opiates) could still be established. The reason for such a potentiation of the activity remains to be elucidated. PMID- 6247161 TI - beta-Adrenoceptor studies. 6. Further investigations on the hybrid nature of the rat adipocyte beta-adrenoceptor. AB - The nature of the rat adipocyte beta-adrenoceptor was studied in further detail using a selected series of tolamol-type beta-adrenoceptor antagonists. Isoprenaline antagonism by these compounds was evaluated on adipocytes, right atrium, left atrium and left hemidiaphragm of the rat. Adipocyte pA2 values were corrected for binding to bovine serum albumin determined separately for each antagonist. A strong correlation between adipocyte and diaphragm pA2 values was found with those antagonists which had an identical N-substituent but a different substitution pattern in the phenoxypropanolamine ring. This relationship was absent with those compounds which had the same 2-methylphenoxypropanolamine moiety but a different N-substituent. With the latter antagonists, however, adipocyte pA2 values correlated significantly with the two cardiac pA2 values. These results support the idea that the interaction site of the rat adipocyte beta-adrenoceptor for the aromatic moiety of arylethanolamines and aryloxypropanolamines has beta 2-characteristics whereas the alkanolamine side chain interaction site has a beta 1-nature. Finally, it was ascertained that the apparently dualistic (beta 1 and beta 2) character of the rat adipocyte adrenoceptor is not due to the presence of both a beta 1- and a beta 2-receptor population on the fat cell plasma membrane. PMID- 6247162 TI - Short-term surgical denervation increases 3H-clonidine binding in rat salivary gland. PMID- 6247163 TI - Effect of intracisternal application of 6-hydroxydopamine on the antihypertensive action of propranolol in the dog. AB - The antihypertensive effects of intravenous (i.v.) and intracisternal (i.cist.) dl-propranolol were studied in anesthetized hypertensive dogs pretreated with i.cist. administered 6-hydroxydopamine (6-OHDA, 600 micrograms/kg) one week previously. Acute neurogenic hypertension was elicited by sino-aortic denervation (deafferentation). In control (saline-pretreated) dogs, dl-propranolol given i.cist. (50 micrograms/kg) or i.v. (0.3 and 1 mg/kg) decreased both the rise in blood pressure and tachycardia induced by deafferentation. These hypotensive and negative chronotropic actions of i.v. (0.3 mg/kg) propranolol were suppressed by pretreatment with 6-OHDA. At a higher dose (1 mg/kg), i.v. propranolol always corrected hypertension and tachycardia in 6-OHDA-treated dogs as in control animals. After 6-OHDA, i.cist. propranolol (50 micrograms/kg) failed to decrease the rise in blood pressure in debuffered animals. Conversely, the bradycardia induced by i.cist. propranolol was more marked in 6-OHDA-treated dogs than in control animals. These results confirm that the antihypertensive action of propranolol can be partly explained by an action on the central nervous system. They support the hypothesis that the hypotension observed after intracisternal (and also after low does of i.v.) propranolol is dependent on the integrity of central catecholaminergic neurons. These studies suggest that the antihypertensive action of propranolol may be partly due to the blockade of central presynaptic beta-adrenoceptors. PMID- 6247165 TI - Effect of indomethacin on the cyclic AMP-dependent protein kinase. AB - Indomethacin inhibited cyclic AMP-dependent protein kinase activity in small intestine in in vivo experiments. An inverse pattern of variation was exhibited by acetyl salicylic acid, eterylate and benorylate, acetyl-p-amino-phenol being inactive. Indomethacin, acetyl salicylic acid, eterylate and benorylate increased the protein kinase activity in liver, lung and heart after in vivo administration. The in vivo effect of indomethacin was confirmed by in vitro experiments with small intestine and heart protein kinases. These results support the concept that indomethacin can affect protein kinase activity in a tissue specific way. PMID- 6247164 TI - Noradrenaline inhibits depolarization-induced 3H-serotonin release from slices of rat hippocampus. AB - The depolarization (26 mM K+)-induced release of 3H-serotonin and 3H noradrenaline from slices of rat hippocampus was studied with a superfusion method. Exogenous NA (in the presence of 10 muM desipramine) inhibited 3H-5-HT release (EC50 3 X 10(-7) M) as well as 3H-NA release (EC50 10(-7) M) by more than 70%. Both of these effects were competitively antagonized by phentolamine, but not by propranolol. It is tentatively suggested that the inhibitory effect of NA on 3H-5-HT release from hippocampus slices reflects the activation of postsynaptic alpha-receptors which are localized on serotonergic nerve terminals. PMID- 6247166 TI - Mouse-killing in rats induces a naloxone-blockable increase in nociceptive threshold. AB - Mouse-killing behaviour in rats increased the nociceptive threshold for paw licking, as measured in the hot-plate test. This effect was prevented by the opiate antagonist naloxone, which, on the other hand, had no influence on mouse killing behavior per se. It is concluded that opioid mechanisms may be involved in changes of nociceptive threshold associated with aggressive behavior. PMID- 6247168 TI - Modulation of ACTH-induced grooming by [Des-Tyr1]-gamma-endorphin and haloperidol. AB - Intraventricular administration of ACTH1-24 into the rat induced excessive grooming behavior. This response could be blocked by local administration of of neuroleptics into either the nucleus accumbens or the neostriatum. Local administration of [Des-Tyr1]-gamma-endorphine (LPH62-77) but not alpha-endorphin (LPH61-76) in either the nucleus accumbens or the neostriatum mimicked the effect of the neuroleptics. A second intraventricular injection of ACTH1-24 4 h after the first did not cause excessive grooming suggesting the development of acute tolerance. Both haloperidol and DT-gamma-E reduced the development of acute tolerance to ACTH-induced grooming. It is suggested the DT-gamma-E modulates the dopaminergic activity underlying the display of ACTH-induced excessive grooming. PMID- 6247167 TI - Postsynaptic alpha 1- and alpha 2-adrenoceptors in the circulatory system of the pithed rat: selective stimulation of the alpha 2-type by B-HT 933. AB - The antagonism by yohimbine (1 mg/kg, i.v.) of vasopressor responses in pithed rats was most pronounced towards B-HT 933 (dose ratio 18.3) and moderate towards clonidine (dose ratio 3.7) and especially L-phenylephrine (dose ratio 2.5). Prazosin (0.1 mg/kg, i.v.) had no effect on the pressor responses to B-HT 933, moderately affected those to clonidine (dose ratio 3.9), but strongly diminished those to L-phenylephrine (dose ratio 53). Phentolamine (1 mg/kg, i.v.) was devoid of a differential antagonism. The results obtained suggest a subclassification of postsynaptic alpha-adrenoceptors into alpha 1- and alpha 2-subtypes mediating pressor effects. B-HT 933 is a selective agonist and yohimbine an antagonist of postsynaptic alpha 2-adrenoceptors. L-Phenylephrine preferably stimulates and prazosin preferentially occupies the alpha 1-adrenoceptors. Clonidine is a potent agonist of both types and phentolamine behaves as a non-selective antagonist. PMID- 6247169 TI - The regulation of cardiac alpha 1-adrenergic receptors by guanine nucleotides and by muscarinic cholinergic agonists. PMID- 6247170 TI - Direct effect of phenylethylamine upon isolated rat aortic strip. AB - Phenylethylamine (PEA) has been implicated in a number of central and peripheral nervous system disorders. Its possible mechanisms of action include stimulation via catecholamine release and direct stimulation by PEA. We have examined the effects of PEA on isolated vascular smooth muscle (VSM) to further explore the mechanism by which PEA produces contraction in this tissue. Helical strips of rat aorta were suspended in a muscle bath. Smooth muscle contractions were recorded via force transducer. PEA elicited a concentration dependent contraction from these strips with a threshold near 10(-6) M and a maximum response at 5 X 10(-3) M. Pretreatment of rats with reserpine dramatically reduced the norepinephrine (NE) content of kidney, heart and spleen of these animals but did not prevent the action of PEA on VSM. The presence of phentolamine (10(-4) M) completely blocked the strip response to PEA. The presence of propranolol (10(-7) or 10(-4) M) altered but did not block the VSM response to PEA. These results argue that the effects of PEA upon the aortic strip preparation involve a direct action of this amine upon VSM. PMID- 6247171 TI - Cell surface changes accompanying aging in human diploid fibroblasts. V. Role of large major cell surface protein and surface negative charge in aging- and transformation-associated changes in concanavalin A-mediated red blood cell adsorption. PMID- 6247172 TI - Characteristics of motor apparatus in testicular, epididymal and ejaculated spermatozoa. A study using demembranated sperm models. PMID- 6247173 TI - Gene expression in normal and virally transformed mouse 3T3b and hamster BHK21 cells. PMID- 6247174 TI - DNA polymerase gamma, cytochrome c oxidase and mitochondrial integrity in rabbit spleen lymphocytes stimulated with concanavalin A. PMID- 6247176 TI - Thymidine phosphorylation in synchronous cultures of Tetrahymena pyriformis GL. PMID- 6247175 TI - Suppression of the transformed phenotype with retention of the viral 'src' gene in cell hybrids between Rous sarcoma virus-transformed rat cells and untransformed mouse cells. PMID- 6247177 TI - In vitro mitogenic and steroidogenic effects of ACTH analogues on an adrenal tumor cell line (Y-1). PMID- 6247178 TI - Sources of direct excitatory and inhibitory inputs from the medial rhombencephalic tegmentum to lateral and medial rectus motoneurons in the cat. AB - The paramedian pontine and bulbar tegmentum was explored by microstimulation to outline the sites of origin of direct excitatory and inhibitory inputs to lateral rectus (LR) and medial rectus (MR) motoneurons (MNs). In order to avoid activation of fibers of passage and axon reflexes originating outside the stimulation sites, experiments were carried out 4--22 days after brain stem transections causing degeneration of vestibulo-ocular pathways. Additionally, in some experiments the paramedian tegmentum was isolated from the contralateral side by midline transections. Mapping of stimulus sites from which monosynaptic EPSPs and IPSPs were elicited brought out the following preoculomotor reticular regions: 1. LR-MNs received monosynaptic IPSPs from the contralateral reticular formation corresponding to Nucl. reticularis points caudalis (R.p.c.) and the rostral part of Nucl. reticularis gigantocellularis (R.gc.). 2. Monosynaptic inhibitory input to MR-MNs could only be demonstrated after degeneration of excitatory pathways ascending from the internuclear neurons of the VIth nucleus and from the ipsilateral vestibular nuclei. Monosynaptic IPSPs originated in the ipsilateral dorso-medial tegmentum through the entire extent of the Nucl. reticularis pontis oralis and rostral R.p.c. including the region of the ipsilateral VIth nucleus. 3. Monosynaptic excitation of LR-MNs was induced by stimulation of the ipsilateral R.p.c. and the rostral half of the paramedian bulbar tegmentum (R.gc.). 4. The sites from which monosynaptic EPSPs were evoked in MR-MNs were confined to the contralateral VIth nucleus and its immediate vicinity. No evidence could be obtained for direct excitatory inputs to MR-MNs from the ipsilateral paramedian tegmentum. It is concluded that the paramedian rhombencephalic reticular formation contains four pools of premotor neurons related to coordination of conjugate horizontal eye movements. Two of them are excitatory for LR- and MR-MNs with ipsilateral ON-directions, the other two mediate reciprocal inhibition of the antagonistic motor nuclei. PMID- 6247179 TI - Thalamocortical transformation of responses to complex auditory stimuli. AB - In unanesthetized guinea pigs, thalamic (CGM), and cortical (auditory I) neurons were recorded simultaneously. Nine of 69 neuron pairs showed a positive cross correlation of their spontaneous activities, with increased discharge probability of the cortical neuron beginning 2--5 ms after the discharge of the CGM-neuron. The individual neurons of such pairs had an identical CF and the same spectral responsiveness. The responses of cortical neurons to pure tones were much more phasic than those of the corresponding CGM-neurons. Thalamic neurons could be driven up to much higher AM- and FM-modulation frequencies (100 Hz) than cortical neurons, which usually ceased to follow AM-frequencies above 20 Hz. Stronger or weaker suppression of tonic response components in cortical and thalamic neurons and the lower AM-range of cortical neurons is related to stronger or weaker intracortical and intrathalamic inhibition respectively. Response characteristics to FM-stimuli are similar to those of AM-stimuli. All CGM and cortical neurons responded to a variety of natural calls of the same or of other species. Responses of CGM-cells represented more components of a call than cortical cells even if the two cells were synaptically connected. In cortical cells, repetitive elements of a call were not represented if the repetition rate was too high. High modulation frequencies within a call, such as those of the fundamental frequency, could still be separated in the response of some CGM-neurons, but never in those of cortical neurons. Both CGM and cortical cells responded essentially to transients (amplitude or frequency modulations) within a call, if spectral components of such elements were within the spectral sensitivity of the cell. Spectral components outside the spectral sensitivity range could result in suppression of spontaneous discharge rate. Responses of cortical and CGM-cells, and thus the representation of call elements by neuronal responses, varied with the intensity of a call. It is suggested that, at higher levels of the auditory system, essential information about the temporal features of complex sounds may be represented by neural responses to transients in various spectral regions. PMID- 6247180 TI - Subthalamic projections to the globus pallidus: an electrophysiological study in the rat. PMID- 6247181 TI - Corticofugal actions on the lateral cervical nucleus of the cat. PMID- 6247182 TI - Glucocorticoid enhancement of guanidine neuromuscular facilitation. PMID- 6247183 TI - Glucocorticoid enhancement of serotonergic facilitation of cat spinal monosynaptic motor neuron excitation. PMID- 6247184 TI - The histochemical behaviour of zinc-activated tartrate-resistant phosphatase (ZnTP) in early stages of experimental tumors in the rat trigeminal nerve. AB - The activity of the ZnTP (Felicetti und Rath 1975; Rath and Felicetti 1975) was investigated histo- and biochemically in neurinomas of trigeminal nerves of rats. The tumors were induced by a single transplacental pulse of 30 mg ENU/kg on the 17th day of gestation. The rats were killed at the age of 40 to 160 days. The activity of the ZnTP is demonstrated histochemically by a coupling azo dye technique with 1-naphthylphosphate after Rath and Felicetti (1975) as well as a lead nitrate method with 4-nitrophenyl phosphate at the age of 40 to 140 days. Biochemical investigations of the trigeminal nerves are performed at the age of 140 and 160 days only. The separation of ZnTP is carried out by isoelectrofocusing in polyacrylamide gels after Felicetti and Rath (1975). Together 14 neurinomas are found in the trigeminal nerves of 53 rats. All neurinomas show a high activity of the ZnTP. The ZnTP activity is absent in normal Schwann cells. Three trigeminal nerves of rats subjects to the transplacental pulse of ENU harbour small foci of ZnTP activity without detectable neoplastic cell proliferation. Similar spots of enhanced ZnTP activity have never been found in control rats. This rises suspicion that the neoplastic proliferation of cells is preceded by the activation of ZnTP. PMID- 6247185 TI - Phagocytosis of inert particles in the reticuloendothelial system in rats with experimental insulinopenic diabetes. AB - Phagocytosis of inert, radioactive gold particles in the reticuloendothelial system in rats in the case of experimental insulinopenic diabetes was studied. In the spleen, phagocytosis was seen to have fallen to a relatively low level after four weeks from the induction of diabetes. In the liver, there was noted a reduction of phagocytosis per gram of organ, though it remained the same for the total organ which in the case of diabetes mellitus increases in weight relative to body weight. This difference in reaction of the reticuloendothelial system in the liver and spleen has also been observed in mice with tumors. The importance of the findings of the present study for increased sensitivity to infections of poorly controlled diabetic patients is discussed in greater detail. PMID- 6247186 TI - Light and electron microscopic evaluation of thymuses from feline leukemia virus infected kittens. AB - Light microscopic and electron microscopic findings in thymuses from 4-week old feline leukemia virus-infected and 4- and 9-week old noninfected kittens were evaluated and found to be morphologically similar to each other. Thymuses from 9 week old feline leukemia virusinfected kittens were markedly atrophied and individual lobules within each thymus varied in the severity of atrophy. Loubules having the least severe atrophy had a moderate thinning of the cortex and a heterogeneous thymuses included intense eosinopoiesis at the corticomedullary junction, increased prominence of vasculature, and enlarged Hassal's corpuscles. In addition to these changes lobules of thymus having the most severe atrophy had a marked cortical thymocyte depletion, lobule collapse, and increased numbers of mast cells. Degeneration of epithelial cells in most lobules was indicated by electronlucency of the cytoplasmic matrix and often greatly dilated rough endoplasmic reticulum. PMID- 6247187 TI - Trypsinogen-kinase from Aspergillus fumigatus. AB - The activation of bovine trypsinogen by an extracellular acid proteinase from A. fumigatus is described. The enzyme activates trypsinogen optimally at pH 3.5 and 32 degrees C. The effect of substrate and enzyme concentrations on the activation has been studied and the Km-value has been determined. PMID- 6247188 TI - Collagen breakdown by gingival collagenase and elastase. AB - The granule fraction of human polymorphonuclear leucocytes (PMNs), the concentrated product of gingival washing from 2 human volunteers and the culture fluid of samples of human gingiva were incubated with neutral salt soluble collagen from rat skin and the patterns of collagen degradation were studied by SDS polyacrylamide gel electrophoresis. Collagenase from human gingiva cleaved the collagen molecules in a fashion similar to that of the PMN granule fraction. Collagen was also attacked by elastase from human PMNs and, to a lesser extent, by elastase from the gingival washings. PMID- 6247189 TI - Effect of fluoride administration on renal glucose-6-phosphatase activity in rats. AB - Renal glucose-6-phosphatase activity was found to be significantly elevated by fluoride administration (NaF 35 mg/kg, i.p.). The elevation of the enzyme activity was markedly suppressed by adrenalectomy. PMID- 6247190 TI - Effects of angiotensin II and of an angiotensin II receptor antagonist on simian virus 40-induced tumor growth in vivo. AB - The effects of angiotensin II and of the competitive angiotensin II receptor antagonist saralasin on in vivo tumor growth were investigated in hamsters. Angiotensin II strongly inhibited tumor growth while saralasin stimulated it, though the high dose used had partial agonistic angiotensin II-like actions. Lower doses of saralasin were without significant effect on tumor weights. PMID- 6247191 TI - Molecular basis for plasmid epidemiology. PMID- 6247192 TI - Adenosine-3,5-phosphate levels in brain structures of rats submitted to four different behavioral procedures. AB - Shuttle avoidance training decreased the cAMP content of rat brain (excluding hippocampus and caudate nucleus), amygdala and hypothalamus. Stimulation by tones alone had a similar effect, but only in the brain fraction. Pseudoconditioning or footshocks alone had no effect. PMID- 6247194 TI - Adrenocorticotrophic hormone and cyclic adenosine monophosphate effect on mouse adrenal cortical cell membrane potential. AB - Adrenocorticotrophic hormone (ACTH) and cyclic adenosine monophosphate (cAMP) both caused a rapid and transient depolarization of the resulting membrane potential of superfused rat adrenal cortical cells. The membrane depolarization to both secretagogues were very similar. The membrane potential changes occurred as early as 0.1 min and were dose dependent in both onset and extent of depolarization. PMID- 6247193 TI - Stimulation of macromolecular synthesis by endotoxin-treated 3T6 fibroblasts. AB - The interaction of endotoxin with cultured fibroblasts resulted in a depression of cellular proliferation and an increased synthesis of macromolecules, namely collagenous and non-collagenous proteins. The collagen salt-soluble fraction was increased at the expense of the insoluble fraction, and both the salt-soluble fraction and collagen secreted into the medium was underhydroxylated. PMID- 6247195 TI - Natural epizootic diarrhea of infant mice (EDIM): a light and electron microscope study. PMID- 6247196 TI - Effect of divalent cations on cyclic AMP formation in human mononuclear leukocytes. PMID- 6247198 TI - Selective methylation of rous sarcoma virus glycoproteins by protein methylase II. PMID- 6247197 TI - [Importance of the components of the complex ester group for the action of acetylcholine and dicarboxylic acid dicholine esters]. AB - The substitution of ether oxygen by a methylene group in the acetylcholine molecule sharply decreases the muscarinic action, while the substitution of the carbonyl group by a methylene one reduces the nicotinic properties. Sebacoyldicholine possesses only nicotinic properties. The replacement of its ether oxygens by methylene groups lowers the stimulant action on the frog rectus abdominis muscle by two orders of magnitude, whereas the stimulant action on the cat sympathetic ganglion is 30-fold as decreased. The blocking action on the isolated rat diaphragm becomes 30-fold less potent, but the blocking action on the cat skeletal muscle remains as strong as that of sebacoyldicholine after cholinesterase inhibition. The replacement of sebacoyldicholine carbonyl groups makes the compound elicit a noncompetitive cholinolytic action on the frog muscle, while the blocking action on the cat skeletal muscle becomes as weak as that exerted by hexadecamethylene-bis-trimethyammonium. PMID- 6247199 TI - Stimulation by LH of cytosolic protein phosphorylation in bovine luteal cells. PMID- 6247200 TI - Regulation by vasoactive intestinal peptide of cyclic AMP accumulation in gastric epithelial glands. A characteristic of human stomach. PMID- 6247202 TI - Assembly of the mitochondrial membrane system. Structure and location of the mitochondrial glutamic tRNA gene in Saccharomyces cerevisiae. PMID- 6247201 TI - Localisation of the transcription initiation site of the chloramphenicol resistance gene on plasmid pAC184. PMID- 6247203 TI - Evidence for the involvement of single-strand DNA-binding proteins in mammalian DNA replication. PMID- 6247204 TI - The oxidation--reduction state of cytochrome oxidase in freeze trapped gerbil brains. PMID- 6247205 TI - Some immunochemical properties of Pseudomonas aeruginosa cytochrome oxidase (or nitrate reductase). PMID- 6247206 TI - Acetaldehyde-enkephalins: pronounced changes in the opiate activity of methionine enkephalin and leucine-enkephalin on reaction with acetaldehyde. PMID- 6247207 TI - Simian virus 40 T-antigen phosphorylation is variable. PMID- 6247208 TI - Amino acid sequence of an active site fragment from human diphosphoglycerate mutase. PMID- 6247209 TI - Phospholamban phosphorylation in the perfused rat heart is not solely dependent on beta-adrenergic stimulation. PMID- 6247210 TI - The terminal step of the de novo synthesis of diacyl and alkylacyl phospholipids in subfractions of rabbit sarcoplasmic reticulum ontogenesis. PMID- 6247211 TI - Structure of bovine cytochrome oxidase. PMID- 6247212 TI - The amino acid sequence of a hinge region in the regulatory subunit of bovine cardiac muscle cyclic AMP-dependent protein kinase II. PMID- 6247213 TI - Influence of endogenous opiates on anterior pituitary function. AB - In general, the endogenous opioid peptides (EOP), morphine (MOR), and related drugs exert similar effects on acute release of pituitary hormones. Thus administration of opiates produces a rapid increase in release of prolactin (PRL), growth hormone (GH), adrenocorticotropin (ACTH), and antidiuretic hormone (ADH), and a decrease in release of gonadotropins and thyrotropin (TSH). Although not yet fully established, there is growing evidence that the EOP participate in the physiological regulation of pituitary hormone secretion. Thus naloxone (NAL), a specific opiate antagonist, has been shown to reduce basal serum levels of PRL and GH, and to elevate serum levels of LH and follicle stimulating hormone in male rats. Other reports have shown that NAL can inhibit the stress-induced rise in serum PRL, raise the castration-induced increase in serum LH to greater than normal castrate values, and counteract the inhibitory effects of estrogen and testosterone on LH secretion. Opiates appear to have no direct action on the pituitary, but there is evidence that they can alter activity of hypothalamic dopamine and serotonin in modulating secretion of pituitary hormones. PMID- 6247214 TI - The effects of opiate agonists on growth hormone and prolactin release in rats. AB - Various opioid receptor agonists, including Met5-enkephalin amide, Leu5 enkephalin amide, [D-Ala]2-Met5-enkephalin amide, [D-Ala]2-Leu5-enkephalin amide, morphine sulfate, d-methadone hydrochloride, and l-methadone hydrochloride were administered to adult male rats by subcutaneous injection. All opioid receptor agonists except Leu5-enkephalin amide significantly stimulated growth hormone and prolactin release. Naloxone and naltrexone blocked the hormone stimulatory effects of the opioids and both naloxone and naltrexone, when administered alone, significantly reduced serum growth hormone and prolactin concentrations. The dopaminergic agonist apomorphine, but not the alpha-adrenergic agonist clonidine, blocked opiate stimulation of prolactin. Morphine sulfate caused growth hormone release in rats pretreated with alpha-methyl-p-tryosine, a catecholamine synthesis inhibitor. Cholinergic agonists, physostigmine and pilocarpine, antagonized the growth hormone and prolactin release induced by morphine sulfate. The data suggest that the opiates stimulate prolactin via an interaction with catecholaminergic neurons controlling prolactin release and stimulate growth hormone via a mechanism independent of alpha-adrenergic or general catecholaminergic influence. The mechanism through which cholinergic agonists act to inhibit opiate agonist stimulation of growth hormone is presently unknown. PMID- 6247215 TI - Effects of exogenous and endogenous opiates on the hypothalamic--pituitary- gonadal axis in the male. AB - Narcotics acutely depress serum testosterone levels in the male. Three mechanisms could be involved: an enhancement of the degradation of testosterone; a direct inhibition of testicular steroidogenesis; or, finally, an inhibition of the hypothalamic-pituitary-luteinizing hormone (LH) axis resulting in a reduction in LH-dependent testicular steroidogenesis. The currently available evidence indicates that narcotics do not affect the catabolism of testosterone by the liver or testicular steroidogenesis. Rather, the data favor a direct action on the hypothalamic--pituitary--LH axis, probably by inhibiting the secretion of LH releasing hormone (LH-RH) from the hypothalamus. The effects of narcotics on serum LH appear to be mediated via specific opioid receptors, suggesting that a naturally occurring opioid-like substance exists that normally inhibits LH. In support of this conclusion, opiate receptor blockers markedly increase serum LH levels shortly after their subcutaneous administration. In addition, endogenous opioids also seem to participate in testosterone's negative feedback control of the hypothalamic--pituitary--LH axis. Thus, it appears that opiate drugs inhibit the function of the hypothalamic-pituitary-gonadal axis by occupying opiate receptors in the hypothalamus and, moreover, that endogenous opioids exist that normally bind to these receptors and regulate activity in this axis. PMID- 6247216 TI - Prolactin as a regulator of fluid and electrolyte metabolism in mammals. AB - The evidence that prolactin is a fluid and electrolyte regulator in mammals is reviewed, with particular emphasis on the renal actions of prolactin. Prolactin receptors are found in mammalian kidneys. Prolactin modulates renal formation of cyclic AMP and polyamines and it leads to demonstrable histological changes in the proximal tubules. The renal actions of prolactin primarily involve modulation of the effects of other hormones and are therefore critically dependent on the background physiological situation. Prolactin seems able to cause a prolonged reduction in water, sodium, and potassium excretion, a pattern that is imitated by no other hormone with the possible exception of growth hormone. Prolactin preparations can cause an acute antidiuresis, which may in part be related to contamination of prolactin preparations with vasopressin. However, most of the described effects cannot be explained by vasopressin contamination. This is particularly so with the effects of prolactin on water movements across fetal skin, the amniotic membrane, and in the eye where prolactin and vasopressin have diametrically opposite effects. It is concluded that prolactin is a regulator of fluid and electrolyte metabolism in mammals but that it is a modulator rather than a primary controlling factor. PMID- 6247217 TI - Role of prolactin in reproduction in male mammals. PMID- 6247218 TI - Mechanism of prolactin action. AB - Most experimental information regarding the mechanism of action of prolactin in its diverse array of target tissues has been discovered using mammary tissues. Evidence has recently been presented that suggests that prolactin may be "internalized" into its target cells and have intracellular actions. Accordingly, it has been reported that prolactin stimulates RNA synthesis in isolated nuclei from mammary tissues; and by immunoflorescent studies, prolactin has been located within its target cells. It has been further suggested from additional experimental studies that the primary action of prolactin may involve its initial interaction with fixed plasma membrane receptor sites. Subsequent actions of prolactin may involve the following: a) an increased intracellular concentration of potassium and a reduced level of sodium, b) an increased level of cGMP and a reduced level of cAMP, c) an enhanced rate of prostaglandin biosyntheesis mediated by a stimulation of phospholipase A2 activity, and d) a stimulation of polyamine synthesis. It has also been shown that the actions of prolactin require calcium ions in the extracellular environment. Laboratory studies have thus indicated that the actions of prolactin may be carried out by a number of processes; but a single, primary action of this hormone that accounts for all of its actions has not yet been proven. PMID- 6247219 TI - Sodium bicarbonate douching for improvement of the postcoital test. AB - In the hope of improving sperm survival within the cervical mucus, 93 infertile patients with unfavorable postcoital tests were advised to douche with a solution of sodium bicarbonate 30 to 60 minutes prior to sexual intercourse. In most patients observed, the repeatedly poor postcoital test improved remarkably, and 31 pregnancies have been achieved. In the majority of patients, the postcoital test was repeated on 2 subsequent days (without and with the benefit of sodium bicarbonate douching) with astonishing differences in the test results. In addition to pH changes, sodium bicarbonate douching resulted in significant alteration of the cervical mucus electrolyte components (detected by scanning electron microscopy and energy-dispersive x-ray analysis). The possible modes of action of sodium bicarbonate douching are fully analyzed. PMID- 6247220 TI - Factors affecting sperm motility. IV. Incubation of human semen with caffeine, kallikrein, and other metabolically active compounds. AB - The effect of six metabolically active compounds, namely caffeine, kallikrein, cyclic adenosine 3':5'-monophosphate, prostaglandin E, triiodothyronine, and insulin on spermatozoal motility was investigated. Hypokinetic and normokinetic semen specimens from fertile and infertile patients were incubated with various concentrations of these compounds. Spermatozoal velocity and percentage of motility were determined periodically with the objective multiple exposure photography (MEP) method before and during the following 4 to 8 hours. No significant differences was found between experimental and control specimens as to these parameters under the influence of the tested compounds, with the exception of caffeine. Caffeine immediately increased the percentage of motile spermatozoa by 30% to 50% of initial values in approximately two-thirds of cases. No influence on sperm velocity was detected during this period. By using the combined MEP and supravital staining techniques it was found that nonmotile live spermatozoa were activated by caffeine without any effect on the percentage of dead sperm. Some practical implications of these findings, the difference between our results and those reported by others, and the mechanism of action of these compounds are reviewed and discussed. PMID- 6247221 TI - Solubilization of chromatin by means of DNase I. AB - The paper describes a technique for obtaining solubilized rat liver chromatin by means of mild cleaving with DNase I. The procedure gives a high yield of macromolecular fragments which can be further fractionated by gel filtration. Separated fractions differ in the rate of incorporation of chromosomal RNA precursors applied in vivo. PMID- 6247222 TI - Activity of phosphatases in Balantidium coli. I. PMID- 6247223 TI - The effects of phospholipase A and lysolecithin on glucose 1,6-diphosphate levels and on the activities of glucose 1,6-diphosphate phosphatase, phosphofructokinase and phosphoglucomutase in the isolated rat diaphragm muscle. PMID- 6247224 TI - Effect of 17 beta-estradiol on thyroliberin responsiveness in GH3/B6 rat prolactin cells. AB - GH3/B6 rat prolactin cells were used to analyse at the cellular level the mechanisms by which 17 beta-estradiol (E2) regulates TRH responsiveness of prolactin cells. Before experiments, cells were grown for up to 7 days in 3 different media: normal medium (N) containing 15% horse serum and 2.5% fetal calf serum, CD medium prepared with charcoal-dextran extracted serum and CDE medium supplemented with 4 x 10(-8) M E2. The binding of 3H-TRH (30 min at 37 degrees C) and the TRH-induced percent increase of prolactin release as a function of TRH doses were compared in the 3 conditions. Preculture in E2 enriched medium increased by 50% the number of TRH high-affinity binding sites without modifying their affinity, increased by up to 3 times the percent of the TRH-induced stimulation of prolactin release and improved by one order of magnitude the ED50 of the TRH effect on prolactin release. The presence of HEPES (10 mM) during TRH challenge masked the effect of E2 on the increase in number of binding sites but respected its potentiating effect on prolactin release. PMID- 6247225 TI - Acquisition of sensitivity to LH in relation to foetal development. Stimulation of cyclic AMP and testosterone production in the rat testis. AB - The ability of LH to stimulate, in vitro, adenylate cylcase activity and testosterone secretion was studied in foetal rat testes after prelabelling with [14C]adenine. As little as 0.1 ng/ml LH produced significant synthesis of cyclic AMP and testosterone secretion. Increase of cyclic AMP production was observed as early as 1 min after addition of LH (100 ng/ml), preceding the rise in testosterone synthesis and secretion. FSH and prolactin were not effective. LH stimulation of cyclic AMP and testosterone production appeared concomitantly in rat foetal testes on day 15 of gestation and reached a maximum on day 18. Immature testes (14 days) developed functional receptors when cultured in a medium devoid of hormone. The results of the present study suggest that cyclic AMP mediates the effect of LH on steroidogenesis in foetal testes and that the differentiation of functional receptors occurs at the same time as the capacity for testosterone synthesis. PMID- 6247226 TI - Differences between dispersed Leydig cells and intact testes in their sensitivity to gonadotrophin-stimulation in vitro after alteration of LH-receptor numbers. AB - The sensitivity to hCG-stimulation in vitro of intact hemi-testes and collagenase dispersed Leydig cells has been compared directly following either an hCG-induced loss of LH-receptors or after a hyperprolactinaemia-induced increase in LH receptors. Injection of hCG 65 h previously, reduced hCG-binding to dispersed Leydig cells by over 84%. The sensitivity of the steroidogenic response of these cells to hCG-stimulation in vitro was reduced 22-fold whereas intact testes from the same animals showed only a 3-fold reduction in sensitivity to hCG. Dispersed Leydig cells from control rats were 8 times more sensitive to hCG-stimulation than intact testes from the same rats, a difference not evident with hCG-injected rats. In contrast, there was no difference between intact testes and dispersed Leydig cells from control and hCG-injected rats in their sensitivity to stimulation with dibutyryl cyclic AMP in vitro. Induction of hyperprolactinaemia increased hCG-binding to dispersed Leydig cells by 55%. The sensitivity of these cells to hCG-stimulation in vitro was increased by a factor of 4.5, a difference not found with intact testes from the same animals. These results show that experimental manipulation of LH-receptor numbers alters the sensitivity of dispersed Leydig cells, but not of the intact testis, to hCG-stimulation in vitro, a difference which appears to reside at the receptor level. Possible explanations for these findings are discussed together with their implications with respect to the distribution of LH-receptors over the Leydig cell surface. PMID- 6247227 TI - Effects of lysosomotropic agents, cytochalasin B and colchicine on the "down regulation" of prolactin receptors in mammary gland explants. AB - Effects of lysosomotropic agents and drugs which disrupt the cytoskeleton on prolactin receptor levels were studied in organ culture of rabbit mammary glands. As we have shown previously, prolactin is able to induce a down-regulation of its own receptor levels. In the present experiments, lysosomotropic agents, chloroquine, ammonium chloride and methylamine, in the presence of prolactin are capable of almost completely preventing this down-regulation. Interestingly, these lysosomotropic agents alone could increase the level of prolactin receptors, which confirms that the degradation of prolactin receptors occurs in the lysosomes and that this is a rapid process which can proceed in the absence of prolactin. The almost complete lack of effect of microfilament (cytochalasin B) or microtubule (colchicine) disrupting drugs seems to indicate that the cytoskeleton is not involved in the down-regulation process. PMID- 6247228 TI - The biosynthesis of ribonuclease and its accumulation in protein bodies in the cotyledons of mung bean seedlings. PMID- 6247229 TI - Morphologic study of cultured pancreatic fetal islets during maturation of the insulin stimulus-secretion mechanism. AB - We recently described a tissue culture system in which 21.5-day-old fetal rat islets underwent an in vitro maturation of insulin stimulus-secretion coupling over a period of 7 days. During the same period, the acinar part of the explanted fragments degenerated and the islets became isolated, seeming to increase in mass. In the present study, we have utilized these characteristic morphologic changes in an attempt to evaluate the extent that apparent islet growth reflects multiplication of preformed beta cells or the neogenesis of these cells from ductular or acinar cells. In the first days of culture, continuity between islets and ducts could be demonstrated, and the islets appeared to "bud" from the ducts. During this time, only insulin- and glucagon-positive cells could be demonstrated immunocytochemically, and the 3H-thymidine incorporation index of the beta cells (expressed as the percentage of beta cells labeled during 24 h or exposure to 3H thymidine and 3 h of "chase") in the "budding" islets was 28.7 +/- 2.6. After 7 days in culture, i.e., after maturation of the insulin stimulus-secretion mechanism, the islets were no longer associated with ductular epithelium. At this stage, insulin-, glucagon-, and occasional somatostatin-positive islet cells could be demonstrated, and the 3H-thymidine incorporation index of the beta cells was significantly decreased to 16.7 +/- 2.8. These observations are taken to support previous suggestions of a possible neogenesis of beta cells from duct epithelium in the rat. This tissue culture technique appears well suited for further detailed studies of this neogenesis. PMID- 6247230 TI - Stimulation of adenylate cyclase by Ca2+ and calmodulin in rat islets of langerhans: explanation for the glucose-induced increase in cyclic AMP levels. AB - The effect of Ca2+ and calmodulin has been studied on adenylate cyclase activity in homogenates of rat islets of Langerhans. EGTA had a stimulatory effect on the enzyme in accord with the known inhibitory effect of Ca2+. In contrast, the addition of Ca2+ together with calmodulin is stimulatory and demonstrates the existence of a Ca2+-dependent adenylate cyclase in islets of Langerhans. It is suggested that the glucose-induced increase in cyclic AMP concentrations in intact islets is a secondary consequence of the glucose-induced increase in cytosol free-Ca2+ concentrations which, with calmodulin, causes an increase in the activity of adenylate cyclase. PMID- 6247231 TI - A decreased response of cyclic adenosine monophosphate concentrations to glucagon in liver slices from streptozotocin-induced diabetic rats. AB - Responses to glucagon from the adenylate cyclasecyclic adenosine monophosphate (cAMP) system in liver slices from control and streptozotocin-induced diabetic rats were compared. Tissue cAMP levels were similar in the basal state but responded poorly to glucagon (20 pg/ml-2 microgram/ml) in diabetic rats. Insulin treatment of diabetic rats in vivo led to a reversal of the glucagon stimulation towards the values in the control rats. The basal and glucagon-stimulated activities of adenylate cyclase in crude membrane fractions were similar in both groups. Plasma immunoreactive glucagon levels in diabetic rats were approximately three times higher than those in normal rats. Liver slices obtained from normal rats, which were injected with glucagon (0.2 mg, i.m.) 45 min previously, also showed an impaired responsiveness to glucagon of tissue cAMP levels, while no significant difference in adenylate cyclase activity was observed between the normal and glucagon-treated rats. These results suggest that the responsiveness of liver slices from the streptozotocin-induced diabetic rat has been modified by the preceding hyperglucagonemia. The reason for the observed differences between slices and crude membranes is not known. PMID- 6247232 TI - Impaired glycogen synthase activating system in human diabetic polymorphonuclear leukocytes. AB - The effects of diabetes mellitus on glycogen synthase and its activating system (synthase phosphatase) were studied using human polymorphonuclear leukocytes (PMN). PMN were obtained from control subjects and diabetic patients by a gradient sedimentation technique. Enzyme activities of endogenous synthase-l and total synthase were not statistically different in diabetic and control cells. For measurement of endogenous synthase phosphatase, cells were sonicated in 50 mM Tris buffer (pH 7.5) and incubated at 30 degrees C. Conversion of synthase-D to l and the maximum percent synthase-l attained were decreased in homogenates of diabetic cells. There was no correlation between the plasma glucose concentration and the rate of conversion of synthase-D to -l. Synthase phosphatase activities were also measured using a purified synthase-D substrate. Under these experimental conditions, glycogen synthase phosphatase activities did not differ in control and diabetic cells. These results are consistent with a diabetes induced defect in conversion of endogenous synthase-D to -l at the level of the synthase enzyme rather than at that of the activating phosphatase. PMID- 6247233 TI - Abnormal sciatic nerve myo-inositol metabolism in the streptozotocin-diabetic rat: effect of insulin treatment. PMID- 6247234 TI - [Incidence of complement fixation antibodies against Rotavirus in children]. PMID- 6247235 TI - Characteristics of osteogenic sarcoma of hamsters induced by BK virus. AB - Two out of 9 weanling hamsters, treated with intravenous inoculation of highly concentrated human papovavirus BK, propagated in human embryonic kidney cells, developed osteogenic sarcomas of the costal cage and the mandibula. The sera of the tumor-bearing animals were positive for BK T-antigen and the successively transplanted tumors were positive for intranuclear T-antigen when tested with anti-SV40 T-antibody by immunofluorescence. The tumor tissue exhibited various stages of maturation, from areas showing immature sarcoma and angiomatous sarcoma to those of well-differentiated osteogenic sarcoma. Tumor histology was described in detail. PMID- 6247236 TI - New methods for the serodiagnosis of hepatitis A. PMID- 6247237 TI - Opiates and acid secretion. PMID- 6247238 TI - [New aspects in ultrasound mammography (author's transl)]. AB - We report about 239 ultrasound examinations of the breast using a new water-tank scanner (U.I.Octoson, Ausonics, Sydney, Australia). A very good tissue differentiation of the brease is caused by a special technique and a high resolution. Beside benign results, typical findings in 49 malignancies are demonstrated ("shadowing", "christmastree-sign") and its value discussed. All ultrasound examinations are correlated to X-ray mammography, thermography, needle biopsy and patho-histology. PMID- 6247239 TI - [The absorption of conjugated oestrogens from the irradiated and non-irradiated vagina (author's transl)]. AB - Eighteen women received for four weeks daily applications of conjugated estrogens in ointment. Seven had had primary irradiation of carcinoma of the cervix and eleven were in the menopausal stage without irradiation. Before the first medication and 1, 2, 4, 6, 8, 12 and 24 hours afterwards the estradiol, FSH and LH levels were estimated and the mean values of the two collectives compared. Cytologic smears of the vaginal wall were taken weekly of three irradiated and seven not irradiated patients. From the results one can draw the conclusion that an absorption of the estrogens through the vaginal wall takes place leading to local as well as systemic effects of the estrogens. However in the radiated patients the absorption of estrogen and maturation of the epithelium was significantly slower than in the not-irradiated group. PMID- 6247240 TI - [On the mechanism of normal and irregular gonadal development (author's transl)]. PMID- 6247241 TI - A new filamentous phage cloning vector: fd-tet. AB - We have constructed a hybrid chromosome composed of the genome of wild-type fd (a filamentous, male-specific bacteriophage) and a segment of transposon Tn10 coding for tetracycline resistance but not including the Tn10 insertion sequences. The hybrid phage infects male E. coli, thereby transducing the infected cells to tetracycline resistance. The phage DNA can also be propagated in F- cells after transfection. This new phage, fd-tet, may be used as a cloning vector to produce large quantities of cloned DNA in single-stranded form. Its usefulness has been demonstrated by cloning of a fragment from bacteriophage lambda. Some unexpected sequence alterations have been identified in lambda cloning experiments. PMID- 6247242 TI - DNA rearrangements in a hybrid plasmid carrying the redB imm region of coliphage lambda. AB - The hybrid plasmid consisting of pSC101 and the redB--N--imm region of phage lambda cI857 persists in cells grown at 30 degrees C but not in cells grown at 37 degrees C. In the latter case the plasmid was found to undergo several modifications. Restriction maps of these new plasmids indicate the following modifications: (1) the insertion of an IS1 element into gene N carried by the lambda fragment; (2) a mutation in the pL oL site of the same fragment, and (3) four large deletions (30 to 50% of the hybrid plasmid) which remove almost the entire lambda fragment. For the latter deletions, one endpoint seems to be fixed in the same restriction fragment of pSC101 while the other endpoint assumes four different positions on the lambda fragment; this might suggest a site-specific recombination event. PMID- 6247243 TI - The nucleotide sequence of the transforming BglII-H fragment of adenovirus type 7 DNA. AB - The nucleotide sequence of the leftmost BglII-H fragment (0--4.5%) of weakly oncogenic human adenovirus serotype 7 (Ad7) has been determined (1568 base pairs). This is the shortest Ad7 DNA fragment reported to transform primary rat cells into an immortal cell line (Dijkema et al., 1979). The l-strand of BhlII-H was found to contain the complete information for a polypeptide of at most 28 051 daltons, followed by the putative promoter site of the next gene. Comparison of the determined Ad7 sequence with that of the corresponding region of non oncogenic Ad5 (Van Ormondt et al., 1978; Maat and Van Ormondt, 1979) showed that the over-all organization of the two DNAs is quite similar, but that the sequences, except in regions of suspected strategic importance, diverge considerably. PMID- 6247245 TI - Packaging of plasmid DNA containing the cohesive ends of coliphage lambda. AB - High yields of ColE1::Tn3-cos lambda plasmid genomes packaged in phage lambda virions (2.10(9) per ml) are produced by thermal induction of E. coli W3350 (lambda cI1857S7) lysogens carrying the plasmid DNA. The plasmid DNA is packaged in the linear form, with the right m' terminus of lambda being associated with the lambda tail. PMID- 6247244 TI - Construction and properties of a ColE1::Tn3-cos lambda plasmid for determining RNA polymerase binding sites on ColE1 and Tn3. AB - To determine the location of the RNA polymerase binding sites on the ColE1 plasmid and Tn3 transposon, a special hybrid ColE1::Tn3-cos lambda molecule was constructed which contains the left arm of phage lambda DNA and the right lambda terminal fragment. This permits orienting ColE1 molecules, since the RNA polymerase binding pattern of these two lambda fragments are known to be distinct. ColE1 DNA contains seven binding sites and Tn3 binds three RNA polymerases, with some of the latter probably involved in the expression of the transposition of functions of this transposon. The relationship of these sites to the positions and orientations of known promoters, transcripts, genes and functions is discussed. PMID- 6247246 TI - Plasmid vectors containing the tryptophan operon promoter suitable for efficient regulated expression of foreign genes. AB - Derivatives of plasmid pBR322 that are suitable for high-level expression of foreign genes have been constructed. The vectors contain the Escherichia coli tryptophan promoter, the trpE gene, and about 15% of the trpD gene. To obtain expression, foreign genes are fused to the trpD gene fragment. After induction of the trp operon with 3 beta-indolylacrylic acid, trp gene products increase at least 50-fold, to account for 55% of the newly synthesised protein and 30% of total protein in the cell. PMID- 6247247 TI - HgiAI: a restriction endonuclease from Herpetosiphon giganteus HP1023. AB - A new class II restriction endonuclease, HgiAI has been partially purified from Herpetosiphon giganteus HP1023. The enzyme activity has been characterized and shown to recognize the family of related hexanucleotide sequences (Formula: see text) where the second and fifth nucleotide pairs are A:T pairs in either orientation. Cleavage occurs as shown, to give DNA fragments with 3'-terminal tetranucleotide extensions. The recognition sites of the enzymes SacI and SstI (Formula: see text) form a subset of the recognition site of HgiAI. One of the four possible tetranucleotide 3'-extensions (cohesive ends), generated by HgiAI is identical with those generated by SacI and SstI, another is identical with that of PstI. HgiAI should be useful for molecular cloning. PMID- 6247248 TI - Construction of new cloning vehicles with genes of the tryptophan operon of Escherichia coli as genetic markers. AB - In vitro recombination techniques were used to construct a series of new cloning vehicles with genes of the tryptophan (trp) operon of Escherichia coli as selective marker. To construct these plasmids we have made a restriction cleavage map of the trp operon for the enzymes AosI, AvaI, BglI, BglII, HindIII, HpaI, PvuII, SalI, SstI and XhoI. The constructed plasmids pHP39, pEP392, pEP3921 and pEP3923 are derived from the amplifiable plasmid pBR345 and carry two or more genes of the trp operon, which are controlled by the trp regulatory elements. Plasmid pEP3921 (7.0 kb) carries intact trpE and trpA genes and contains single BglII and SstI sites in trpE, a single HindIII site located between trpE and trpA, and single EcoRI, SalI and XhoI sites located outside the trp genes. Plasmid pEP121 (12 kb) is similar to pEP3921, but has an extra selective marker conferring bacterial resistance to ampicillin. Plasmid pEP3923 (7.4 kb) comprises intact trpB and trpA genes and single BglII, HindIII, EcoRI, SalI and XhoI sites. Plasmids pHP39 (9.8 kb) and pEP392 (9.8 kb) carry an intact trp operon and have two and one EcoRI site, respectively. Plasmid pHP3 (18 kb) carries an intact trp operon and markers for tetracycline and ampicillin resistance. PMID- 6247249 TI - The nucleotide sequence of the right-hand terminal SmaI-K fragment of adenovirus type 2 DNA. AB - The primary structure of the SmaI-K fragment of adenovirus type 2 (Ad2) DNA has been determined. This region includes one of the origins of DNA replication (Winnacker, 1978; Sussenbach and Kuijk, 1978). A leader sequence for an early mRNA in region 4 (Berk and Sharp, 1977; 1978) has also been mapped in this region. The comparison of the primary structure of this region in Ad2 DNA with the corresponding region in Ad5 DNA shows a remarkable homology which may be significant in view of the fact that Ad2 and Ad5 DNAs can interchangeably function in the in vitro replication system of Challberg and Kelly (1979). PMID- 6247250 TI - [Properties of E. coli, Salm. typhimurium and Cl. perfringens strains isolated from soil containing bacterial insecticides based on Bac. thuringiensis]. PMID- 6247251 TI - Carcinoma metastatic in the cervix. PMID- 6247252 TI - Malignant mixed Mullerian tumor of the fallopian tube. Report of a case and review of literature. PMID- 6247253 TI - Oat cell carcinoma of the uterine cervix in a pregnant woman treated with cis diamminedichloroplatinum. PMID- 6247254 TI - Utilization of glucose and celloboise by the microflora of soil enriched with cellulose. AB - The ability of soil microflora to utilize glucose or celloboise was found to depend on previous incubation of the soil with glucose, celloboise or cellulose. Glucose was utilized more rapidly than cellobiose in soil preincubated with glucose or cellobiose. The opposite situation was observed in soil preincubated with cellulose. In the presence of a mixture of both sugars the rate of utilization of one of them was decreased by the second and this decrease could be characterized as competitive inhibition. Glucose accumulated in the medium during utilization of cellobiose alone in soil preincubated with cellulose. This phenomenon was not observed during the utilization of cellobiose in soil preincubated with glucose or cellobiose. PMID- 6247255 TI - The priming effect of glucose in soil sterilized by gamma-radiation and reinoculated with Cellulomonas sp. AB - Mineralization of native organic matter and U-14C-glucose was followed by measuring the formation of CO2 and its radioactivity in chernozem soil presterilized by gamma-radiation and inoculated with a washed suspension of Cellulomonas sp. cells. The introduced bacteria mineralized the soil organic component to a higher extent in variants enriched with glucose. This so-called priming effect of glucose was observed also in the presence of chloramphenicol, inhibiting the growth of the bacteria. The increased mineralization of the native soil organic fraction was also detected in samples that were not enriched with glucose when the bacterial suspension was first disintegrated ultrasonically and the material then used for the inoculation. Possible participation of phenomena of the type of cometabolism and activation of cell membrane transport mechanisms on the occurrence of the priming effect of glucose in the soil is discussed. PMID- 6247256 TI - Effect of starch and inorganic nitrogen on microbial transformations of organic compounds in soil. AB - It was found in long-term incubation experiments (100 weeks) that in soil non amended with organic compounds, mineralization proceeded in a steady state after an initial reactive respiration and corresponded approximately to the rate of mineralization of soil organic matter under natural conditions. The addition of nitrogen influenced this mineralization process only very slightly. The addition of starch decreased the stability of organic compounds in the soil at first but the newly formed organic substances were gradually stabilized again. The addition of nitrogen to starch increased the extent and the rate of these alterations. The overall extent of mineralization of the substrate after the addition of starch alone exceeds the amount of the added substrate; a small accumulation of the substrate could be observed after the addition of starch together with nitrogen. PMID- 6247257 TI - Contents, accumulation and release of energy in green, dead and decomposing plant materials in an upland grassland near Kamenicky, Czechoslovakia. AB - The energy content was studied in above-ground live plant material and in litter in a natural grassland ecosystem with dominant Nardus stricta L., defined phytosociologically as Polygalo-Nardetum strictae. PREISING 1950 corr. OBERDORFER 1957, and in two of its fertilized variants in the course of 1975 to 1977. Based on the determined production characteristics and data on decomposition processes, the amounts of energy accumulated by the green parts of the stands and the amount of energy released during decomposition from the litter were calculated. Changes in the energy content of litter in different stages of decomposition were determined. With progressing decomposition the energy content per gram ash-free decomposing plant litter increases. PMID- 6247258 TI - [The condition of long-term survivors and patients cured of childhood neoplasms]. AB - Throughout the past years, permanent cure has become the realistic goal of treatment in a great number of children with cancer. As therapy is aggressive, various late effects of treatment have to be considered. The long-term survivors of 668 children with cancer treated at the Dept. of Pediatrics, University of Mainz, were analyzed for: their present clinical and neurological status, sensory function, impaired skeletal growth, risk of cardiomyopathies, renal functions after treatment for Wilms' tumors, chronic hepatitis, endocrine disorders, electroencephalographic abnormalities, motor and sensory nerve conduction velocities, death as a late consequence of tumor therapy, risk of second malignant neoplasias, and their psychosocial and intellectual situation. As a general result, the number of possible late consequences is great. Cancer treatment of children should be restricted to specialized teams at pediatric tumor centers. This is important concerning an optimal therapy as well as long term care in view of prevention and early detection and treatment of late sequelae of tumors and treatment. PMID- 6247259 TI - Usefulness of orally active angiotensin I converting enzyme inhibitor (SQ 14,225) in the treatment of malignant hypertension. PMID- 6247260 TI - Inhibitory effects of a pineal extract on adrenal cortex. Lack of competition with ACTH. AB - The purpose of the present investigation was to study the mode of action of a crude aqueous pineal extract (CAPE) on corticosterone (B) production from ACTH mediated isolated adrenal cortex cells. Corticosterone production from a heterogenous adrenal cortex cell population, isolated from 8 male Sprague-Dawley rats, was measured fluorimetrically. CAPE (25 microliters) was tested in this system using ACTH (0--5,000 pg/ml) and dibutyryl-c-AMP (0--100 nM/ml) as stimuli for a period of 1 h. In a separate experiment, CAPE (25 microliters) was administered to ACTH (50 pg/ml) stimulated adrenal cortex cells for 15, 30, 60, and 120 min incubation periods. CAPE significantly decreased B produced by adrenal cortex cells at all doses of ACTH administered. CAPE also decreased the B produced by adrenal cortex cells when dibutyryl-c-AMP was used as a stimulus. The inhibitory effect of CAPE was manifest at some point in time between 30 and 60 min. It was significant at 60 min and highly significant at 120 min. It is evident from these data that CAPE and ACTH are not competing for the same receptor site. PMID- 6247261 TI - Degradation of 2'-5'-linked oligoriboadenylates by 3'-exoribonuclease and 5' nucleotidase from calf thymus. PMID- 6247262 TI - A mental health center's aftercare specialty service for discharged state hospital patients. AB - To serve discharged state hospital patients from its catchment area, a mental health and retardation center established an ambulatory community service that has total responsiblity for the community care of those patients. The service is staffed primarily by mental health workers and nurses. They become members of the neighborhood-based teams on the state hosptial unit and take part regularly in discharge planning with patients and hospital staff. They also provide a range of continuing outpatient and support services, including medication review, development of housing placements and recreational activities, and psychiatric follow-up. The service operates as a specialized, autonomous unit, which allows it to shift staff resources in line with changes in patient and program needs, to allocate time for program development, and to pressure other agencies to develop needed services. PMID- 6247263 TI - A program to improve aftercare in a rural area. AB - A pilot project for improving aftercare in a rural area places the responsibility of aftercare on the project staff rather than on the hospital staff or referral agency personnel. Three counselors cover 31 counties in the catchment area. They contact patients before discharge and again within one month after discharge. When the patient is receiving the desired aftercare, the counselor steps aside, but maintains contact with the referral agency and is available to help the patient when necessary. A study of 23 patients after the first year of the program showed that the average number of days each spent in the hospital during one year dropped from 159 to 49, and the average yearly cost of hospitalization per patient decreased from 8614 dollars to 3384 dollars. Two brief case examples show that the program also has enhanced the quality of life for many of the discharged patients. PMID- 6247264 TI - In vitro inactivation of complement by a serum factor present in Junin-virus infected guinea-pigs. AB - A serum factor(s) of guinea-pigs infected with Junin virus, the etiological agent of Argentine haemorrhagic fever, is endowed with a potent anticomplementary activity. It is resistant to heat (56 degrees, 30 min) and elutes from a Sephadex G-200 column between albumin and haemoglobin. It is ineffective in the presence of EDTA or EGTA and does not sediment at 82,000 g. It has no direct effect on C4 unless functional Cl is present. However, it induces Cl activation that consumes C4 haemolytic activity in normal human and guinea-pig sera. The evidence presented in this report demonstrates that the complement activation observed in experimental Argentine haemorrhagic fever is at least in part due to a direct effect of this serum factor on the classical complement pathway. PMID- 6247266 TI - Decreased Beta-adrenoreceptor responsiveness as related to age, blood pressure, and plasma catecholamines in patients with essential hypertension. AB - The role of the sympathetic nervous system as it relates to adrenoreceptor mediated hemodynamic responses was investigated in patients with essential hypertension and in normal subjects of similar age. An age-related increase in plasma norepinephrine (PNE) concentrations observed in 36 recumbent normal subjects (r = 0.623, p less than 0.001) was not found in 56 patients; the latter included some young patients with high values. Sympathetic overactivity in patients (n = 24) as compared with normotensive subjects (n = 20) was suggested by a greater increase in PNE upon standing (242 +/- 34 vs 155 +/- 25 pg/ml (SEM), p less than 0.05) and persistently higher plasma epinephrine (PE) concentrations at rest and during equieffective exercise (p less than 0.05). In patients, PNE was directly related to systolic (r = 0.57, p less than 0.01) and diastolic (r = 0.53, p less than 0.01) blood pressure. Older age was associated with diminished exercise tachycardia and increased blood pressure responses to exercise, which were both more pronounced in hypertensive patients. This higher pressure/lower heart rate pattern was paralleled by an age-related decrease in isoproterenol sensitivity in normal subjects (0.97 +/- 0.15 in six below age 34 years, 1.31 +/- 0.30 in eight between 35--49 years, and 1.82 +/- 0.12 microgra/m2 in six above 50 years), which was also more pronounced (p less than 0.05) in hypertensive patients (1.20 +/- 1.18 in seven below age 34 years, 2.42 +/- 0.30 in nine between 35--49 years, and 6.73 +/- 2.44 micrograms/m2 in eight above 50 years). Thus, an increase in the patients' blood pressure and age is associated with a progressive reduction in beta-adrenoreceptor sensitivity and/or reactivity. Defective beta-adrenoreceptor-mediated responses may result in unopposed alpha adrenoreceptor-mediated vasoconstriction and thereby contribute to the development of hypertension. PMID- 6247265 TI - Modulation of human neutrophil function by monohydroxy-eicosatetraenoic acids. AB - The generation from arachidonic acid and purification of large quantities of a series of monohydroxy-eicosatetraenoic acids (HETEs) which differed only in the position of the hydroxyl group permitted an in vitro analysis of the relative effects of the HETEs on a variety of human neutrophil functions. All of the HETEs elicited maximal neutrophil chemotactic responses of comparable magnitude, but the chemotactic potencies exhibited a distinct rank order with 5-HETE greater than 8-HETE:9-HETE (85:15, w:w) greater than 11-HETE=12-L-HETE. Peak chemotactic responses were achieved at concentrations of 1 microgram/ml for 5-HETE, 5 microgram/ml for 8-HETE:9-HETE and 10 microgram/ml for 11-HETE and 12-L-HETE. In the absence of a concentration gradient, the HETEs were similar in potency with respect to the stimulation of neutrophil chemokinesis and the enhancement of the expression of neutrophil C3b receptors. At optimally chemotactic and chemokinetic concentrations, none of the HETEs stimulated the generation of superoxide by neutrophils, altered the expression of neutrophil IgG-Fc receptors, or evoked the release of lysosomal enzymes. Methyl esterification of 5-HETE and 12-L-HETE reduced the chemotactic activity to less than 12% of that of the parent compound. The HETE methyl esters competitively inhibited the chemotactic activity of the homologous free acids by approximately 50% at equimolar concentrations, without inhibiting the chemotactic activity of formyl-methionyl peptides or of chemotactic fragments of the fifth component of complement (C5fr). The stimulus specificity of the competitive inhibition of chemotaxis by HETE methyl esters and the functional selectivity of the HETEs as compared to the formyl-methionyl peptides and C5fr, which stimulate neutrophil oxidative metabolism and lysosomal enzyme release, suggest that HETEs activate human neutrophils by a unique mechanism. PMID- 6247267 TI - Augmentation of centrally induced alpha-adrenergic vasodepression in spontaneously hypertensive rats. AB - Central alpha-adrenergic mechanisms for cardiovascular regulation were studied by injecting phenylephrine into a recipient rat whose head was isolated from its body by cross perfusion with a donor rat. Blood pressure increases produced in the donor were accompanied by concurrent reduction of blood pressure and sympathetic nerve activity in the recipient rat's body. These effects were abolished when alpha-adrenergic receptors in the perfused head were blocked with phentolamine. By contrast, intracarotid injections of angiotensin increased blood pressure not only in donor but also in recipient rats. The magnitude of phenylephrine-induced vasodepression was significantly greater in spontaneously hypertensive rats (SHR) than in normotensive or DOCA-salt hypertensive ones. Distribution of radioactive microspheres indicated that carotid arterial blood went mainly to the cerebrum, midbrain, and hypothalamus, with almost negligible amounts going to the lower brainstem. Collectively, our results suggest that centrally administered phenylephrine reduces sympathetic vasomotor tone and blood pressure by acting on alpha-adrenergic receptors located in supramedullary brain areas (possibly in the hypothalamus). In SHR, augmented, vasodepressor responsiveness may be due to reduced brain levels of endogenous norepinephrine that could increase the alpha-adrenergic receptors available. PMID- 6247268 TI - Possible role of phosphorylation-dephosphorylation in the regulation of calcium metabolism in cardiovascular tissues of SHR. AB - Spontaneously hypertensive rats (SHR) and Wistar-Kyoto normotensive rats (WKY) were compared for phosphorylation-dephosphorylation mechanism(s) in aorta, caudal artery, inferior vena cava, and right and left ventricles. Reduction of cAMP induced phosphorylation of microsomes and cAMP-dependent protein kinase activity was significant in the aorta and caudal artery of SHR compared with WKY. These changes were not observed in the vena cava of SHR. Phosphoprotein phosphatase activity was significantly increased (p less than 0.05) in the soluble fraction of arterial smooth muscle. No changes were observed, however, in the myocardium or vein. Furthermore, the extent of phosphorylation, and Ca2+ uptake ability and the protein kinase activity in the soluble and the microsomal fractions were not reduced in the myocardium of SHR compared with WKY. These data suggest that phosphorylation-dephosphorylation mechanisms are altered in the microsomal fraction of the aorta and caudal artery of SHR, which may result in reduced Ca2+ uptake by the intracellular organelle. The changes observed could have a significant effect on vasodilatation of arteries in the hypertensive state. The lesion appears specific to the arterial smooth muscle in the cardiovascular tissues. PMID- 6247270 TI - Hypocholesterolaemic effects of dietary fibre. AB - Role of dietary fibre in lowering serum cholesterol has been studied in mongrel dogs. Pectin, wheat bra, guar gum and Isabghol were fed with standard diet. No statistically significant changes were found in serum cholesterol levels in any groug (P greater than .05) after one week. Later by 15th day, pectin reduced serum cholesterol significantly i.e. 12.4% (P less than .02). However, in groups being fed other forms of fibre the levels of serum cholesterol were reduced by 3.8% to 7.0 PMID- 6247269 TI - Discrepancy between antihypertensive effect and angiotensin converting enzyme inhibition by captopril. AB - Captopril, an inhibitor of angiotensin converting enzyme, was administered twice daily to 13 hypertensive patients for a mean period of 9 weeks. Continuous blood pressure control in the ambulatory patients was established with a portable blood pressure recorder. Notwithstanding, in eight patients with normal renal function, plasma converting enzyme was found to resume normal activity before administration of the morning dose of captopril. Only in 5 patients with impaired renal function did some blockade of plasma converting enzyme persist for more than 12 hours. Measured plasma converting enzyme activity seemed to reflect total conversion of angiotensin I, including conversion in the pulmonary vascular bed, since changes in its activity were closely paralled by changes in plasma aldosterone levels. Bradykinin accumulation seems unlikely when converting enzyme and thus, presumably, kininase II has resumed normal activity. Captopril administration does not seem to alter plasma epinephrine or norepinephrine levels. Blood pressure reduction in the face of normal angiotensin converting enzyme activity is probably due to hyporesponsiveness of the arterioles to pressor hormones, which may be due to specific renin-related and/or nonspecific effects of captopril. PMID- 6247271 TI - Blockade by burimamide of the effects of clonidine on cardiac contractility phosphorylase activation and cyclic adenosine monophosphate in isolated guinea pig heart. AB - Clonidine in a dose-range of 2.5 microgram to 80 microgram caused positive inotropic effect, which was accompanied by increase in the cyclic AMP levels and phosphorylase-activation of the isolated perfused guinea pig heart. Clonidine induced biochemical and mechanical effects were blocked by burimamide, an H2 receptor antagonist Propranolol (1 x 10(-6)M), phentolamine (1 x 10(-6)M) or reserpine pretreatment, did not affect the clonidine responses on the perfused guinea pig heart. Clonidine reduced the 4-methyl-histamine (H2-agonist) responses of guinea pig heart. Our data suggest that the cardiac effects of clonidine may be due to stimulation of H2-type of receptors. PMID- 6247272 TI - Restriction endonucleases in identification of a genome type of adenovirus 19 associated with keratoconjunctivitis. AB - Adenovirus type 19 (Ad19) was first associated with disease in 1973 when several outbreaks of keratoconjunctivitis were reported from Europe and North America. We have examined Ad19 isolates by deoxyribonucleic acid restriction with BamHI, BglI, and SmaI restriction endonucleases. All keratoconjunctivitis-associated Ad19 isolates were identical but different from the Ad19 prototype. The total number of resolved restriction fragments of the Ad19 prototype genome was 31, only 17 of which migrated as the restriction fragments of keratoconjunctivitis associated genomes. We conclude that two different genome types of Ad19 exist, one of which has been responsible for the recent outbreaks of keratoconjunctivitis. PMID- 6247273 TI - Shift in the prevalent human rotavirus detected by ribonucleic acid segment differences. AB - Rotavirus was purified from nine patients hospitalized with acute gastroenteritis from October to December, 1978, in Mexico City. Analysis of their ribonucleic acids by gel electrophoresis showed the presence of two distinct patterns (2s and 22) which had been observed in 1977, but which now were found in a very different proportion: the pattern called 2s, observed in only 11% (6 of 52) of the patients in 1977, was found in 90% (8 of 9) of the patients in 1978. Improvements in the electrophoretic method allowed us to observe differences in the migration of up to seven segments between the two patterns and to distinguish small differences in one or two segments within either of the two ribonucleic acid patterns. PMID- 6247274 TI - Complement-dependent antiviral monospecific antibody-mediated lysis of murine cells coated with Sendai virus or its envelope component. AB - Complement-dependent antiviral antibody-mediated lysis of murine cells coated with Sendai virus or its envelope component (P815 mastocytoma cells and L929 cells) was studied with antiviral monospecific sera (anti-F and anti-HN sera). Three types of interactions different in terms of susceptibility of complement dependent antibody-mediated lysis were distinguished: (i) fusion-positive Sendai viruses induced the susceptibility with both anti-F and anti-HN sera; (ii) fusion negative envelope particles with F protein induced the susceptibility with only anti-F serum; (iii) noninfectious Sendai viruses with F0 protein induced no susceptibility. The lack of complement-dependent antibody-mediated cytolysis susceptibility in case (iii) was found to be due neither to detachment of cell associated noninfectious virus in the presence of antiserum nor to antibody mediated particular redistribution of cell surface virus antigens. Differences in virus or envelope component-cell association in these three cases were discussed. PMID- 6247275 TI - Significance of bursa of Fabricius as target organ in infectious bursal disease of chickens. AB - The highly virulent strain Cu-1 of infectious bursal disease virus caused 100% mortality in 4-week-old specific pathogen-free chickens. In contrast, chickens infected after bursectomy did not become sick and only showed some discrete and transient necrosis in lymphatic tissues. However, these chickens contained infectious virus and, subsequently, produced specific antibodies. The virus concentrations in the organs studied reached their maximum 2 days postinfection, but were about 1,000 times lower in non-bursectomized animals. It may be assumed that in bursectomized chickens the early events of infection are the same as in non-bursectomized ones. Virus is spread in varius organs, but due to the absence of a sufficient number of susceptible cells, virus multiplication is moderate and can be kept in check by the host defense mechanism. With the occurrence of circulating specific antibodies the virus can be rapidly eliminated. The studies particularly stress that the availability of a large number of highly susceptible cells is a crucial point in acute viral infections. PMID- 6247276 TI - Pathology of chickens infected with avian nephoblastoma virus MAV-2(N). AB - A neophroblastoma-inducing myeloblastosis-associated virus, MAV-2(N), derived from avian myeloblastosis virus was characterized with respect to biochemical composition and avian pathogenesis. Purified fibroblast-grown virus contained the same size 35S ribonucleic acid and the same relative amounts of viral polypeptides as another myeloblastosis-associated virus inducing predominantly osteopetrosis MAV-2(O). Plaque-purified MAV-2(N) induced a 76 to 93% incidence of nephroblastoma and a 3 to 50% incidence of osteopetrosis in SPAFAS and line 15 x 7 chickens: the oncogenic spectrum and the onset of nephroblastoma varied with the line of chicken and the route of injection. Renal neoplasms were manifest in chickens older than 2 months and grew to a massive size. Furthermore, 29% of control chickens housed with MAV-2(N)-infected chickens demonstrated nephroblastoma. MAV-2(N)-infected chickens had growth rates and blood packed cell volumes comparable to those of uninfected chickens. Infected chickens 2 months of age had increased kidney, liver, and spleen weights; tumor-bearing chickens 3 to 4 months of age had increased liver, lung, brain, pancreas, and bone weights. The concentration of albumin was decreased and the concentration of gamma globulin was increased in the serum of MAV-2(N)-INFECTED CHICKENS. Analysis of the sera of nephroblastoma-bearing chickens for virus and antibody showed that three states existed: (i) high levels of neutralizing antibody, (ii) high levels of virus, and (iii) simultaneous presence of both at low levels. The pathological and virological features of MAV-2(N) which distinguish it from MAV-2(O) are discussed. PMID- 6247277 TI - Antiviral cell-mediated immune responses and effect of chromosome polymorphism in Herpesvirus saimiri-infected monkeys. AB - Herpesvirus saimiri is a horizontally transmitted virus of squirrel monkeys (Saimiri sciureus) which, when inoculated into owl monkeys (Aotus trivirgatus), induces fatal malignant lymphoma in 75 to 80% of the animals. Previous immunological and virological studies have not indicated why 20 to 25% of inoculated owl monkeys develop a chronic, disease-free H. saimiri infection. In the present study, we examined two parameters to explain why certain owl monkeys are resistant to H. saimiri-induced disease. The first possibility was that the animals in which H. saimiri established a chronic infection were all of the same karyotypic class. In studying four such animals, we found that three of the seven known karyotyes were represented, indicating that chromosome polymorphism does not explain disease resistance. The second possibility examined was that animals which develop disease do so as a result of a failure in specific anti-H. saimiri cell-mediated immunity. Naturally infected squirrel monkeys exhibited long lasting, virus-specific cell-mediated immunity in a lymphocyte proliferation assay, whereas such reactivity could not be demonstrated either in chronically infected owl monkeys or in an owl monkey with a primary H. saimiri infection. The failure of owl monkeys to respond to viral antigens was not due to a basic immunological defect, since these animals gave normal responses to heterologous cells and were capable of being sensitized with the protein antigen keyhole limpet hemocyanin. PMID- 6247278 TI - Biological activities of fragments derived from Bordetella pertussis endotoxin: isolation of a nontoxic, Shwartzman-negative lipid A possessing high adjuvant properties. AB - Endotoxin from fresly sedimented Bordetella pertussis cells, isolated by the phenol/water procedure when submitted to kinetically controlled, mild acidic hydrolysis released a polysaccharide (polysaccharide 1), a complex lipid (lipid X), and a glycolipid. When treated with somewhat stronger acid, the glycolipid yielded a second polysaccharide (polysaccharide 2) and another complex lipid (lipid A). The intact pertussis endotoxin had all the usual properties of endotoxins extracted from enteric bacteria. Lipid X and the intermediary glycolipid retained all the endotoxic properties of the unfractionated endotoxin. In lipid A, pyrogenicity was reduced to a very low level and toxicity and Shwartzman reactivity were absent; however, this fraction retained most of the endotoxin's antiviral activity, and its adjuvant power was considerably higher than that of the intact endotoxin. Lipid A elicited nonspecific resistance against challenge with certain bacteria, but not against others. PMID- 6247279 TI - Role of specific cytotoxic lymphocytes in cellular immunity against murine cytomegalovirus. AB - Cytotoxic lymphocytes were generated in vitro against murine cytomegalovirus (MCMV)-infected cells by incubation with ultraviolet light-irradiated, infected fibroblasts. When passively transferred, they reduced virus titers in spleens of mice 1 day after infection with MCMV. Protection was abrogated by anti-theta serum and complement. Spleen cells from mice infected for 6 to 14 days protected mice better than cells from mice after infection for 1, 3, or 30 days. Protection by in vitro- and in vivo-generated cells was H-2K or H-2D restricted. Specific cytotoxic T lymphocytes are therefore present and operative during acute MCMV infection. However, MCMV infection inhibited the development of primary cytotoxic response against ectromelia virus. It also suppressed the ability of lymphocytes from mice with established memory for ectromelia to develop secondary cytotoxic cells in vitro, and it inhibited the development of memory cells for the cytotoxic response to ectromelia virus. In view of these data and the inability of animals recovering from MCMV infection to eliminate all infected cells, the cytotoxic response to MCMV may be qualitatively or quantitatively deficient. PMID- 6247280 TI - In vitro studies of interaction of rickettsia and macrophages: effect of ultraviolet light on Coxiella burnetii inactivation and macrophage enzymes. AB - The inactivation of Coxiella burnetii in suspension or in cultures of guinea pig peritoneal macrophages by ultraviolet (UV) light was studied. The effect of UV treatment on the activity of macrophage organelle marker enzymes and their subsequent equilibration in linear sucrose gradients was also determined. It was shown that UV treatment of 600 mu W/cm2 for 15 s at a distance of 10 cm inactivated C. burnetti, either in suspension (10(8) organisms per ml) or within guinea pig peritoneal macrophages. Similar UV treatment had little effect on the activity or equilibration of macrophage organelle marker enzymes in linear sucrose gradients. However, longer exposure caused considerable inactivation of these enzymes. PMID- 6247281 TI - Murine cytomegalovirus: detection of latent infection by nucleic acid hybridization technique. AB - The technique of nucleic acid hybridization was used to detect the presence of murine cytomegalovirus (MCMV)-specific deoxyribonucleic acid (DNA) in cell cultures and salivary gland tissues. The presence of approximately 4.5 and 0.2 genome equivalents per cell of MCMV-specific DNA was identified in cultures of salivary (ISG2) and prostate gland (IP) cells, respectively. These cells, derived from animals with experimentally induced latent infections, were negative for virus-specific antigens by immunofluorescence and on electron microscopy revealed no visible evidence of the presence of herpesviruses. A cell line derived from the salivary gland of an uninoculated animal (NSG2) was also found to possess MCMV-specific DNA (0.2 genome equivalents per cell). For this reason, salivary gland tissues from uninoculated animals supplied as "specific pathogen-free" mice by three commercial sources were tested upon arrival for the presence of MCMC specific DNA. MCMV-specific DNA was detectable in pooled salivary gland extracts from uninoculated animals derived from two commercial sources. All of these animals were seronegative and virus negative by conventional infectivity assays. PMID- 6247282 TI - Curing of a plasmid is correlated with an attenuation of virulence in the marine fish pathogen Vibrio anguillarum. AB - The transposon A sequence Tn1 containing the ampicillin resistance determinants was transposed from RP4 to a plasmid of the marine fish pathogen Vibrio anguillarum. Curing experiments in which plasmid loss was determined by analysis of the segregation of the ampicillin resistance phenotype showed the association of virulence with the specific V. anguillarum plasmid class. PMID- 6247283 TI - Alveolar macrophage ingestion and phagosome-lysosome fusion defect associated with virus pneumonia. AB - Virus-induced suppression of pulmonary phagocytic defenses is associated with defects in the intracellular processing of bacteria by alveolar macrophages. To determine whether the intracellular defect is related to a failure in phagosomelysosome fusion, mice were infected with a sublethal dose of Sendai virus, and the capacity of phagocytic cells, obtained by lung lavage, to exhibit phagosomelysosome fusion was quantitated during the course of the viral infection. Lysosomes of alveolar macrophages were prelabeled with acridine orange, the cells were challenged with Candida krusei, and fusion was determined with fluorescence microscopy by the discharge of the dye into the yeast containing phagosome. Ultrastructural cytochemical studies verified the validity of the fluorescent fusion assay. Simultaneous experiments were performed to determine whether the viral infection also suppressed phagocytic ingestion by alveolar macrophages. Phagosome-lysosome fusion was progressively inhibited during the viral infection, reaching a low at day 7 when only 13 +/- 3% of the phagocytic cells fused as compared with 97 +/- 3% in cells from uninfected control animals; respectively, 55 +/- 5% as compared with 74 +/- 2% of the phagocytic cells contained yeasts. Thereafter, phagosome-lysosome fusion progressively increased reaching near normal levels (92 +/- 3%) on day 17 of the infection. At the same time period, phagocytic uptake was enhanced to a level where 97 +/- 3% of the cells contained yeasts. These data demonstrated that virus induced suppression of intrapulmonary killing of bacteria involves functional lesions that retard the ingestion of inhaled organisms by alveolar macrophages and inhibit intracellular processing by degradative lysosomal enzymes by interfering with phagosome-lysosome fusion. PMID- 6247284 TI - Different polypeptide composition of two human rotavirus types. AB - Human rotaviruses, which are placed into two groups according to their ribonucleic acid patterns obtained by gel electrophoresis, were characterized both by polypeptide components from purified virions and by polypeptides translated from their denatured ribonucleic acids in rabbit reticulocyte lysates. Viruses assigned to different groups differed in the electrophoretic migration of the second largest of the polypeptides which compose the inner shell; polypeptides that had been synthetized in vitro from ribonucleic acid from each group showed this same difference, thus indicating that this is due to the genomic composition. This study suggests that there are differences in the third largest polypeptide of the inner shell and also in the three smaller polypeptides composing the outer shell. We also demonstrated that there are differences in genomic and polypeptide compositions between simian (SA11) and calf (Nebraska calf diarrhea virus) rotaviruses grown in tissue culture and human rotaviruses. PMID- 6247285 TI - Immunoglobulin E in patients with Japanese encephalitis. AB - Significantly high levels of immunoglobulin E in the acute sera of encephalitis cases (suspected or confirmed as Japanese encephalitis) declined sharply during early convalescence. PMID- 6247286 TI - Participation of three major glycoprotein antigens of herpes simplex virus type 1 early in the infectious cycle as determined by antibody-dependent cell-mediated cytotoxicity. AB - Tissue culture cells infected with herpes simplex virus type 1 synthesize three major glycoprotein antigens (Ag-11, Ag-8, and Ag-6), which have been characterized by crossed immunoelectrophoresis. The three viral antigens have been identified as a mixture of gA and gB (Ag-11), gD (Ag-8), and gC (Ag-6). Recent findings have shown that antibodies directed to each of the three antigens individually are able to mediate antibody-dependent cell-mediated cytotoxicity when tissue culture cells late in the infectious cycle (18 h postinfection) are used. In this work, antibody-dependent cell-mediated cytotoxicity was applied to study the time postinfection at which the individual viral antigens first made their appearance at the cell surface. All three viral antigens (Ag-11, Ag-8, and Ag-6) could be demonstrated as newly synthesized from 3 to 4 h postinfection, and the quantities of the antigens at the surfaces of the infected cells increased with time postinfection. The use of cycloheximide and ultraviolet-inactivated virus demonstrated that input virus could be detected by antibody-dependent cell mediated cytotoxicity during the first 2 h postinfection, but the cytotoxicity caused by input virus remained constant with time postinfection. In conclusion, these observations demonstrate the participation of individual herpes simplex virus surface antigens in antibody-dependent cell-mediated cytotoxicity attack on cells early in infection. PMID- 6247287 TI - Hepatitis A virus in the liver and intestine of marmosets after oral inoculation. AB - A total of 12 seronegative marmosets (Saguinus mystax) were inoculated orally with hepatitis A virus (HAV) and sacrificed at 3- to 4-day intervals. Tissues from the livers, intestines, mesenteric lymph nodes, and spleens were obtained for immunofluorescence studies, and bile and intestinal contents were obtained for enzyme-linked immunosorbent assay studies. Two marmosets sacrificed on days 34 and 41 after inoculation developed antibody to HAV and demonstrated HAV in their livers but not in any part of their intestinal tissues. None of the remaining marmosets sacrificed from days -3 to 31 survived long enough to develop antibody to HAV, but an additional two marmosets, which were sacrificed on days 21 and 31, demonstrated HAV in their livers and also in bile but not in the intestinal tissues or their contents. The mesenteric lymph nodes and spleens were negative for HAV by immunofluorescence in all the marmosets. No evidence of HAV replication was demonstrated in any part of the intestine at any time during the incubation period or during acute illness in the marmosets inoculated orally with HAV. The shedding of HAV in stools in the late incubation period can be explained by excretion of HAV from the livers with the bile. PMID- 6247288 TI - Adenine nucleotide degradation by the obligate intracellular bacterium Rickettsia typhi. AB - Adenosine 5'-triphosphate (ATP) was catabolized by whole cells and cell-free extracts of Rickettsia typhi to adenosine 5'-diphosphate (ADP) and then to adenosine 5'-monophosphate (AMP), the end product of ATP catabolism under the experimental conditions used. The only intermediate of the pathway from ATP to AMP which was identified by thin-layer chromatography and quantitated by the (14)C content was ADP, whereas products such as adenine, adenosine, hypoxanthine, inosine, and inosine 5'-monophosphate were not detected. The enzymes which could be theoretically responsible for the catabolism or the anabolism of AMP were not detected by standard assay procedures. Most importantly, 5'-nucleotidase or nonspecific phosphatase and AMP nucleosidase activities were undetectable under a variety of experimental conditions. Although these two enzymes remove AMP from the adenylate pool in other cells, they are apparently nonfunctional in R. typhi. The biosynthesis of ATP was initiated by adenylate kinase because no adenine phosphoribosyltransferase or adenosine kinase could be detected. Furthermore, AMP was transported intact without prior dephosphorylation. These observations suggest that for R. typhi the in vivo activity of adenine nucleotide interconversion was limited to the nucleotides, with AMP being the end product of ATP catabolism, and that the salvage of purine bases and nucleosides was not an essential feature of purine metabolism. These results elucidate the findings of a previous study which showed that in the absence of glutamate as a source of energy, the adenylate energy charge of resting cells of R. typhi is drastically lowered by the high proportion of AMP. PMID- 6247289 TI - Interaction of the antiallergic agent AA-344 with biogenic amines and prostaglandins in production of cyclic AMP in rat mast cells. AB - AA-344, which has been evidenced to inhibit selectively IgE-mediated allergic reactions, exhibited an inhibitory effect on cyclic AMP phosphodiesterase (PDase) in the homogenates of purified rat peritoneal mast cells (RMC). AA-344 showed synergistic effects with epinephrine, isoproterenol or prostaglandin E2 and F2 alpha in increasing cyclic AMP level in RMC: the combinations caused an increase in cyclic AMP 30-160 times as much as that caused by the respective agent alone. In the latter effect, AA-344 was at least 1,000 times as potent as theophylline. On the other hand, histamine or serotonin with or without AA-344 had no effect on the RMC cyclic AMP. These results obtained in vitro suggest that AA-344 may exert antiallergic action by increasing cyclic AMP via an interaction with epinephrine or prostaglandins which might be endogenously involved in regulation of a function of RMC in allergic reactions. PMID- 6247290 TI - Nonparticipation of C1q in the decrease of complement activity in the cold in sera of patients with chronic liver diseases. AB - Serum and plasma samples taken simultaneously from 560 patients with various diseases were examined for hemolytic complement activity (CH50) after incubation at 4 degrees C for 20 h. Serum CH50 titers less than 20 U/ml were observed in 39 cases and among them, a difference between serum and plasma CH50 of more than 5 U/ml were observed in 16 cases. Diagnosis of most of them were chronic liver diseases. To analyze the dissociation of CH50 titers between serum and plasma, sequential estimations of CH50 were performed on serum and plasma samples which showed the dissocation incubated at 4 and 37 degrees C. Marked decrease in CH50 titers was obtained in sera but not in plasma incubated at 4 degrees C. In such sera, however, no significant decrease of protein amount and agglutinating activity of C1q was observed. The result could indicate that C1q would not participate in the decrease of serum hemolytic activity in the cold, suggesting an activation of complement other than the classical pathway. PMID- 6247291 TI - Review: effect of anti-ulcer drugs on gastric mucous barrier and possible cyclic AMP involvement. AB - Since cimetidine in spite of its ulcer-healing properties was found to have a damaging effect on gastric mucus, the problem of the influence of anti-ulcer drugs on mucous barrier became of topical interest. The effects of various anti ulcer drugs on gastric mucus secretion are briefly reviewed and the possible role of changes in cyclic AMP levels of gastric mucosa is discussed. PMID- 6247292 TI - Isolation and characterization of beta-lipotropin and adrenocorticotropin from turkey pituitary glands. AB - Beta-Lipotropin and corticotropin have been isolated in highly purified form from turkey pituitary glands. The isolated hormones were characterized by NH2-terminal residue, amino acid and sequence analyses. Their hormonal activity and immunoactivity were also investigated. PMID- 6247293 TI - Sodium-potassium-dependent ATPase. I. Cytochemical localization in normal and cataractous rat lenses. AB - Biochemical studies have demonstrated the presence of ouabain-sensitive Na-K ATPase in lens epithelium. The development of certain experimental cataracts has been associated with the decrease in the level of activity of this enzyme. Cytochemical investigations at the ultrastructural level to localize this important enzyme in the ocular lens are needed to exhibit the site of Na-K-ATPase action. In this investigation cytochemical methods originally described by Ernst for the localization of Na-k-atpase through K-NPPase reaction have been used for normal and cataractous ocular lens. The reaction product was observed to be present on the lateral and apical portion of the epithelial cell membranes. Mooreover, the membranes of the cortical fibers in the anterior polar and equatorial region of the lens also exhibited reaction product of Na-k-atpase. The presence of ouabain reduced the reaction product of Na-K-ATPase; however, continuous exposure to ouabain during preincubation fixation, and incubation demonstrated greater reduction in enzyme action in the lens. The Na-K-ATPase activity in the lenses of animals fed galactose decreased with increase in time on galactose diet. In this study, using ultrastructural cytochemistry, we have demonstrated gradual decrease in Na-K-ATPase activity in the lenses of galactose fed animals. PMID- 6247294 TI - Isolation of the plasma membrane from corneal endothelial cells. AB - The plasma membtanes of normal rabbit endothelail cells were isolated by the use of an aqueous two-phase polymer system. The membrane fraction was identified by electron microscopy, and a fivefold to eightfold increase in the specific activity of two plasma membrane markers. Na+-K+-ATPase and 5'nucleotidase was found. Recovery of the enzyme markers averaged 45% and 22%, respectively. Analysis of the purified membranes for glucose-6-phosphatase, a marker for endoplasmic reticulum, showed no contamination by this structure. This method for cell membrane characterization is promising in determining the enzymatic alterations of diseased corneas. PMID- 6247295 TI - Methyl group deficiency in nerve tissue: a hypothesis to explain the lesion of subacute combined degeneration. PMID- 6247296 TI - The pathology of carcinoma of the lung: the pattern over 15 years. PMID- 6247297 TI - Endocrine effects of tumours of the liver. PMID- 6247298 TI - Lung endocrine tumours. AB - The structure of bronchial carcinoids, oat cell carcinomas and pulmonary 'tumourlets' is described and evidence presented that they are related histogenetically, all being derived from certain specialized cells of endocrine or chemoreceptor nature found within the lining epithelium of the airways. Chemoreceptors related to pulmonary blood vessels have also been identified and two different types of pulmonary tumour have both been termed chemodectoma in the belief that they arise from such structures: these are the so-called multiple minute chemodectoma and the larger solitary variety but the exact histogenesis of both these tumours must remain conjectural at present. PMID- 6247299 TI - Lead poisoning: an ongoing pediatric nursing concern. PMID- 6247300 TI - Characterization of Na-K-ATPase in dog tracheal epithelium: enzymatic and ion transport measurements. AB - The dog tracheal epithelium actively secretes Cl and absorbs Na. The possible dependency of this electrolyte transport on a Mg-dependent, Na-K-activated adenosine triphosphatase (Na-K-ATPase, EC 3.6.1.3) was examined. The characteristics of this enzyme system were investigated using homogenates of tracheal epithelium. The electrical properties and ion fluxes of this epithelium were determined in tissues mounted in Ussing chambers. Addition of Na and K produced an approximate 50% activation of basal Mg-ATPase activity. The apparent Km values for ATP, Na, K, and Mg were 0.4, 12.7, 1.9, and 1.6 mM, respectively. The total specific ATPase activity was 8.1 +/- 0.4 and that of the Mg-ATPase 4.3 +/- 0.1 mumol Pi. mg protein -1.h-1. Addition of ouabain (1 muM) or omission of K from the submucosal bathing solution reduced potential difference (PD) and short circuit current (SCC) significantly. Relatively low concentrations (0.1 mM or less) of ethacrynic acid, furosemide, or 2,4-dinitrophenol (2,4-DNP) depressed SCC and PD significantly, i.e., at concentrations that were without effect on the Na-K-ATPase activity. Ethacrynic acid inhibited Cl secretion, whereas 2,4-DNP lowered both Na and Cl transport. These data demonstrate that 1) the tracheal mucosa of dogs contains a Na-K-ATPase at relatively high specific activity, 2) this enzyme is likely contained in the basal aspect of this membrane, 3) it appears to be essential for maintenance of Cl secretion, and 4) Cl secretion can be reduced (by ethacrynic acid, furosemide, and 2,4-DNP) without Na-K-ATPase inhibition. PMID- 6247301 TI - Innervation of airway smooth muscle in the baboon: evidence for a nonadrenergic inhibitory system. AB - The distribution of receptors and the innervation of intrapulmonary and extrapulmonary baboon airways were examined using tissue bath techniques. Acetylcholine and histamine (via H1-receptors) elicited contractions of all airways. Norepinephrine had both an excitatory (via alpha-receptors) and inhibitory (via beta-receptors) effect in trachealis strips, but in intrapulmonary airways, only inhibitions were observed. Transmural electrical stimulation of resting airways produced sustained contractions that were blocked by either 5 x 10(-6) M tetrodotoxin or 10(-6) M atropine. Electrical stimulation also caused relaxations of histamine-induced contractions in airways pretreated with 10(-6) M atropine and 10(-6) M phentolamine. Relaxations were blocked by 10 x 10(-6) M tetrodotoxin but were unaffected by either 10(-6) M propranolol or 10( 5) M guanethidine. The response of airways to exogenous ATP depended on the degree of active tone. ATP caused contractions in resting airways and airways with moderate tone. In contrast, ATP relaxed airways with high active tone. We conclude that a nonadrenergic system constitute the primary inhibitory innervation of baboon airways, but whether ATP might act as the neurotransmitter could not be determined. PMID- 6247302 TI - Implementation of a campus nursing and health information center in the baccalaureate curriculum. Part II: center project health fairs. PMID- 6247303 TI - Implementation of a campus nursing and health information center in the baccalaureate curriculum. Part III: independent study project. PMID- 6247304 TI - Speech compression: options for speeding nursing education. PMID- 6247305 TI - Social learning theory as a basis for teaching decisions. PMID- 6247306 TI - Survey of nurse attitudes toward professional nursing practice. PMID- 6247307 TI - The professional patient session as a technique for teaching the gynecological examination to nurse practitioner students. PMID- 6247308 TI - Involving undergraduate students in faculty research. PMID- 6247309 TI - International collaboration in nursing education: the people to people approach. PMID- 6247310 TI - Organizational patterns of baccalaureate nursing programs. PMID- 6247311 TI - Implementation of a campus nursing and health information center in the baccalaureate curriculum. Part I. overview of the center. PMID- 6247312 TI - Persistence of pseudorabies virus in infected swine. AB - The persistence of pseudorabies virus (PRV) in pigs clinically recovered from the disease was detected by culture of tissue fragments. Weanling pigs were infected by intranasal instillation of 200,000 plaque-forming units of a strain of PRV isolated from sick pigs in Iowa, and virus was recovered from them 6 weeks to 13 months later. Tonsil, trigeminal ganglia, or pooled trigeminal ganglia and olfactory and optic nerve tissue were most consistently the source of virus. The tissue-fragment culture technique was compared with a co-culture technique for detection of virus in tissue specimens from the recovered pigs. Use of these procedures provided the means to detect PRV in pigs for periods longer than previously recognized. PMID- 6247313 TI - Enterobacter cloacae outer membrane permeability to ceftizoxime (FK 749) and five other new cephalosporin derivatives. AB - The ability of ceftizoxime to penetrate the outer membrane was compared with those of five other new cephalosporins: cefotiam, cefuroxime, cefotaxime, cefmetazole and cefoxitin, using a clinical isolate of Enterobacter cloacae as a test strain. Estimation of permeability was performed by a method utilizing the inhibitory activities of the cephalosporins against beta-lactamase located in the periplasm. Of the cephalosporins tested, both ceftizoxime and cefmetazole gave remarkably high concentrations in the periplasm, several times higher than those of cefotaxime and cefoxitin and ten or more times higher than those of cefuroxime and cefotiam. The approximate permeability coefficient of ceftizoxime was also several times higher than those of cefotiam and cefmetazole and over ten times higher than those of cefoxitin, cefuroxime and cefotaxime. PMID- 6247314 TI - The polymyxin sensitivity and the phosphatidyl ethanolamine content of the Vibrio cholerae membranes. AB - The phospholipid composition of three different strains of Vibrio cholerae was determined by quantitative two-dimensional thin-layer chromatography. The polymyxin sensitivity of the whole organisms or of the liposomes derived from the total phospholipids of these organisms depended solely on the phosphatidyl ethanolamine content of the system concerned and could be quantitatively related by the equations Y1 = 1.074 X1 - 9.828 and Y2 = 1.22 X2 - 34.47 where Y represents the maximum lysis (%)/hr and X, the % phosphatidyl ethanolamine content of the system concerned, the suffix 1 and 2 corresponding to the liposomal and the whole organisms respectively. The analysis revealed the requirement of a threshold amount of phosphatidyl ethanolamine for the expression of polymyxin action on the system concerned. PMID- 6247315 TI - Effect of hormone injections on fatty acid composition of lipid in muscle and liver tissues of New Zealand white rabbits. PMID- 6247316 TI - Clavulanic acid and CP-45,899: a comparison of their in vitro activity in combination with penicillins. PMID- 6247317 TI - Rapid spectrophotometric method for the determination of beta-lactamase activity. PMID- 6247318 TI - Cloning and restriction mapping of the trmA gene coding for transfer ribonucleic acid (5-methyluridine)-methyltransferase in Escherichia coli K-12. AB - A hybrid plasmid from the Clarke and Carbon collection has been isolated. This plasmid carries the trmA gene of E. coli, which is necessary for the formation of 5-methyluridine (m5U,ribothymidine) present in all transfer ribonucleic acid (tRNA) chains of the organism so far sequenced. A restriction map of the argCBH trmA regions is presented. By using cloning in vitro, the trmA gene was located on a 2.9-kilobase pair deoxyribonucleic acid (DNA) fragment. These results and comparison with lambda dargECBH transducing phages established the gene order: argECBH trmA bfe in the 88-min region of the E. coli chromosomal map. Plasmids carrying this 2.9-kilobase pair DNA fragment overproduce the enzyme tRNA(m5U)methyltransferase (EC 2.1.1.35) 20 to 40 times. When this 2.9-kilobase pair chromosomal DNA fragment was expressed in a minicell system, a polypeptide of a molecular weight of 42,000 was synthesized. This polypeptide was tentatively identified as the tRNA(m5U)methyltransferase. These results support the earlier suggestion that the trmA gene is the structural gene for the tRNA(m5U)methyltransferase. PMID- 6247319 TI - RsaI: a new sequence-specific endonuclease activity from Rhodopseudomonas sphaeroides. AB - A new type II sequence-specific endonuclease, RsaI, has been identified from Rhodopseudomonas sphaeroides strain 28/5. An RsaI purification scheme that yields enzyme which is free of contaminating exonuclease and phosphatase activities after a single column fractionation has been developed. The enzyme recognized the tetranucleotide sequence 5'-GTAC-3' and cleaved between the T and A, thereby generating flush ends. RsaI should be extremely useful in deoxyribonucleic acid sequencing experiments. PMID- 6247320 TI - Regulation of lysine- and lysine-plus-threonine-inhibitable aspartokinases in Bacillus brevis. AB - Further studies on the expression of the two aspartokinase activities in Bacillus bovis are presented. Aspartokinase I (previously shown to be inhibited and repressed by lysine) was found to be repressed by diaminopimelate in the wild type strain. However, in a mutant unable to convert diaminopimelate to lysine, starvation for lysine resulted in an increase in aspartokinase I activity. Thus, lysine itself or an immediate metabolite was the true effector of repression. Aspartokinase II (previously shown to be inhibited by lysine plus threonine) was repressed by threonine. Studies with the parent strain and auxotrophs inidicated that only threonine or an immediate metabolite of threonine was involved in this repression. Methionine and isoleucine were not effectors of any of the detected aspartokinase activities. Apart from inhibition and repression controls, a third as yet undefined regulatory mechanism operated to decrease the levels of both aspartokinases as growth declined, even in mutants in which repression control was absent. In thiosine-resistant, lysine-excreting mutants with elevated levels of aspartokinase, the increase in activity could always be attributed to one enzyme or the other, never both. The existence of separate structural genes for each aspartokinase is therefore suggested. PMID- 6247321 TI - Polarity of Tn5 insertion mutations in Escherichia coli. AB - We assessed the effect of insertions of the kanamycin resistance transposon Tn5 in the lac operon of Escherichia coli on the expression of distal genes lacY and lacA (melibiose fermentation at 41 degrees C and thiogalactoside transacetylase synthesis, respectively). Every insertion mutation tested (41 in lacZ and 23 in lacY) was strongly polar. However, approximately one-third of the insertion mutants expressed distal genes at low levels due to a promoter associated with Tn5. To localize this promoter, we (i) reversed the orientation of Tn5 at several sites and (ii) replaced wild-type Tn5 with several substitution derivatives which lack Tn5's central region. Neither alteration changed the expression of distal genes. Thus, in contrast to transposons IS2 and TnA. Tn5's ability to turn on distal gene expression is not due to a promoter in its central region and therefore is not dependent on the overall orientation of Tn5 in the operon. Our results suggest that the promoter is within 186 base pairs of the ends of Tn5. It is possible that the promoter is detected in only a fraction of insertions because it overlaps Tn5-target sequence boundary. PMID- 6247322 TI - Peptone induction and rifampin-insensitive collagenase production by Vibrio alginolyticus. AB - Vibrio alginolyticus produces an extracellular collagenase which requires specific induction by collagen or its high-molecular-weight fragments. Peptone also induces collagenase during the late exponential and early stationary growth phases. The peptone inducers have been shown to have a broad molecular weight range between 1,000 and 60,000. The peptone inducers supported slow growth of V. alginolyticus when supplied as the sole nitrogen source in minimal medium. Digestion of the peptone inducers with purified V. alginolyticus collagenase resulted in a decrease in their inducing ability, whereas digestion with trypsin or alpha-chymotrypsin did not. This indicated that induction by the inducers required the presence of collagenase-sensitive bonds. Prolonged digestion of the inducers with collagenase did not completely eliminate the inducing ability of the inducers. The peptone inducers acted as inhibitors of collagenase. A minimal medium induction system has been developed which involves resuspending cells at high density in a medium containing succinate, (NH(4))(2)SO(4), KH(2)PO(4), and the peptone inducer. Cells grown in minimal medium induce earlier than cells grown on peptone, Casamino Acids, or tryptone. Collagenase production was shown to occur for 30 to 60 min in the presence of rifampin at levels which completely inhibit the incorporation of [(3)H]uracil into trichloroacetic acid-precipitable material. Chloramphenicol completely and immediately abolished collagenase production, which together with labeling studies has confirmed that collagenase production involves de novo synthesis of the enzyme. Both glucose and Casamino Acids repressed collagenase production, although synthesis of the enzyme continued for 30 to 60 min after their addition. The repression of collagenase production by glucose and Casamino Acids was more severe than the inhibition of enzyme formation due to addition of rifampin. PMID- 6247324 TI - Location of the multivalent control site for the ilvEDA operon of Escherichia coli. AB - A strain of Escherichia coli K-12 containing a deletion extending from early in the ilvE gene toward the ilvG gene was shown to exhibit a higher expression of the downstream genes, ilvD and ilvA, than did an ilv+ strain. The elevated expression was under apparently normal ilv-specific control, however. The deletion was transferred to the ilv region of lamba h80dilv and shown by restriction endonuclease and heteroduplex analysis to extend through the deoxyribonucleic acid (DNA) shown, in the preceding paper (C. S. Subrahmanyam, G. M. McCorkle, and H. E. Umbarget, J. Bacteriol 142:547--555, 1980), to contain the ilvO determinant. The deletion was also transferred to an ilv-lac fusion strain and shown to cause an increase in beta-galactosidase formation while allowing retention of ilv-specific control. Transducing phages excised from these fusion strains with and without the ilvO determinant were compared. The phage carrying the ilvO+ determinant contained ilv DNA extending only into but not through the ilvG gene. It did not exhibit an ilv-specific control of beta-galactosidase formation. The phage carrying the deletion of ilvO but containing ilv DNA extending beyond the ilvG gene exhibited ilv-specific control of beta galactosidase formation. It was concluded that the multivalently controlled ilv specific promoter affecting ilv operon expression lies upstream from ilvG and that the ilvO region in the wild-type K-12 strain is a region of polarity preventing ilvG expression and reducing ilvEDA expression. PMID- 6247323 TI - Effect of mitochondrial functions on synthesis of yeast cytochrome c. AB - The effects of the mitochondrial protein synthesis inhibitor chloramphenicol and the mitochondrial F0 adenosine triphosphatase inhibitor oligomycin on the synthesis of nucleus-encoded cytochrome c protein were studied. Both inhibitors stimulated cytochrome c protein synthesis in the derepressed state (growth in media containing 2% raffinose) but had no effect on the synthesis of the cytochrome c protein in the repressed state (growth in media containing 5% glucose). Oligomycin uncoupled the synthesis of the apoprotein from its processing into the hemoprotein. Neither antibiotic had a significant effect on the rate of glucose repression of cytochrome protein synthesis. The kinetics of cytochrome c derepression and the effects of these two antibiotics on these kinetics were also studied. Cells were derepressed by transfer from glucose- to faffinose-containing media, and the rate of cytochrome c synthesis increased from the repressed to the derepressed level during the second hour of derepression. Chloramphenicol delayed this derepression, but after 5 h the rate of cytochrome c protein synthesis increased to twice the rate of synthesis in uninhibited cells. On the other hand, oligomycin inhibited derepression of cytochrome c. These results are discussed with respect to the effects of mitochondrial function in the derepressed and repressed states and during the processes of repression and derepression of cytochrome c. PMID- 6247325 TI - Integration of specialized transducing bacteriophage lambda cI857 St68 h80 dgnd his by an unusual pathway promotes formation of deletions and generates a new translocatable element. AB - Molecular and genetic studies have revealed that several illegitimate recombinational events are associated with integration of the specialized transducing bacteriophage lambda cI57 St68 h80 dgnd his into either the Escherichia coli chromosome or into a plasmid. Most Gnd+ His+ transductants did not carry the prophage at att phi-80, and 10% were not immune to lambda, i.e., "nonlysogenic." Integration of the phage was independent of the phage Int and Red gene products and of the host's general recombination (Rec) system. In further studies, bacterial strains were selected which carried the phage integrated into an R-factor, pSC50. Restriction endonuclease analysis of plasmid deoxyribonucleic acid (DNA) purified from these strains showed that formation of the hybrid plasmids resulted from recombination between a single region of pSC50 and one of several sites within the lambda-phi 80 portion of the phage. Furthermore the his gnd region of the phage, present in the chromosome of one nonlysogenic transductant, was shown to be able to translocate to pSC50. Concomitant deletion of phage DNA sequences or pSC50 DNA was frequently observed in conjunction with these integration or translocation events. In supplemental studies, a 22- to 24 megadalton segment of the his-gnd region of the chromosome of a prototrophic recA E. coli strain was shown to translocate to pSC50. One terminus of this translocatable segment was near gnd and was the same as a terminus of the his-gnd segment of the phage which translocated from the chromosome of the nonlysogenic transductant. These data suggest that integration of lambda cI857 St 68 h80 dgnd his may be directed by a recombinationally active sequence on another replicon and that the resulting cointegrate structure is subject to the formation of deletions which extend from the recombinationally active sequence. Translocation of the his-gnd portion of the phage probably requires prior replicon fusion, whereas the his-gnd region of the normal E. coli chromosome may comprise a discrete, transposable element. PMID- 6247326 TI - Regulation of fatty acid degradation in Escherichia coli: isolation and characterization of strains bearing insertion and temperature-sensitive mutations in gene fadR. AB - Transposon Tn10 was used to mutagenize the fadR gene in Escherichia coli. Mutants bearing fadR:Tn10 insertion mutations were found to (i) utilize the noninducing fatty acid decanoate as sole carbon source, (ii) beta-oxidize fatty acids at constitutive rates, and (iii) contain constitutive levels of the five key beta oxidative enzymes. These characteristics were identical to those observed in spontaneous fadR mutants. The constitutive phenotype presented by the fadR:Tn10 mutants was shown to be genetically linked to the associated transposon-encoded drug resistance. These results suggest that the fadR gene product exerts negative control over the fatty acid degradative regulon. The fadR gene of E. coli has been mapped through the use of transposon-mediated fadR insertion mutations. The fadR locus is at 25.5 min on the revised map and cotransduces with purB, hemA, and trp. Three-factor conjugational and transductional crosses indicate that the order of loci in this region of the chromosome is purB-fadR-hemA-trp. Spontaneous fadR mutants were found to map at the same location. Strains that exhibit alterations in the control of the fad regulon in response to changes in temperature were also isolated and characterized. These fadR(Ts) mutants were constitutive for the fad enzymes at elevated temperatures and inducible for these activities at low temperatures. The fadR(Ts) mutations also map at the fadR locus. These results strongly suggest that the fadR gene product is a repressor protein. PMID- 6247327 TI - Deoxyribonucleic acid sequence of araBAD promoter mutants of Escherichia coli. AB - The controlling site region for the araBAD operon is defined, in part, by two classes of cis-acting constitutive mutations. The aralc mutations allow low-level constitutive expression of ara-BAD in the absence of the positive regulatory protein coded for by the araC gene, whereas the araXc mutations allow expression of araBAD in the absence of the cyclic adenosine monophosphate receptor protein. Six independently isolated aralc mutations and three independently isolated araXc mutations were cloned onto the plasmid pBR322 using in vitro recombinant deoxyribonucleic acid techniques and in vivo recombination between plasmid and chromosomal deoxyribonucleic acid. The location of these mutations was determined by deoxyribonucleic acid sequence analysis. All of the aralc mutations occurred at position -35 within the araBAD promoter (+1 = messenger ribonucleic acid start for araBAD) and resulted from an AT leads to GC transition. All of the araXc mutations occurred at position -10 within the araBAD promoter and resulted from a GC leads to AT transition. Models are presented to explain the mode of action of the aralc and araXc mutations. PMID- 6247328 TI - Intramolecular transposition and inversion in plasmid R6K. AB - Selection was made in Escherichia coli K-12 recA hosts carrying plasmid R6K for ampicillin hyperresistance. Twenty-two selected strains were found to carry mutant plasmids, which, from electron microscopy and restriction enzyme analysis, were concluded to arise by a duplication of transposon Tn2660, which confers ampicillin resistance, in all cases the duplicate transposon being in an inverted orientation with respect to the resident Tn2660. A mutant of R6K, pSJC301, which was temperature sensitive for ampicillin resistance was produced by in vitro hydroxylamine treatment of R6K deoxyribonucleic acid. A plasmid hybrid, pSJC102, was constructed by cloning the EcoRI R6K fragment carrying the wild-type beta lactamase gene into the EcoRI site of ColE1. pSJC301 and pSJC102 were transformed into the same recA host strain to form a stable biplasmid strain. Ampicillin hyperresistant mutants were selected from this strain and screened for plasmids with a duplication of transposon Tn2660, which occurred with equal frequency in either pSJC301 or pSJC102; of 12 characterized, all were inverse repeats of the resident transposon. All six Tn2660 inserts into pSJC301 determined temperature sensitive ampicillin resistance, and all six inserts into pSJC102 determined wild type ampicillin resistance, from which it was inferred that transposition of a duplicate Tn2660 occurs predominantly as an intramolecular event, at least in the multicopy R6K plasmid. In all 28 insertion mutants of R6K, there was an inversion of the deoxyribonucleic acid between the two transposons, whereas in only one of six insertion mutants of pSJC102, inversion had occurred. These results are discussed in terms of current models of transposition. PMID- 6247329 TI - Transposon-mediated conjugational transmission of nonconjugative plasmids. AB - When coresident with conjugative plasmid pNC21, the nonconjugative deletion F prime pJC59, which retains the F transfer origin oriT, was transmitted to transconjugants at a frequency comparable to that of pNC21. In addition, pJC59 was transmitted as an independent plasmid, physically separate from pNC21, an example of plasmid donation. In contrast, two plasmids that are derived from F and deleted for the oriT site, pJC61 and pML31, were transmitted at frequencies 10(4) lower than that of pNC21. This low-frequency transmission was associated with the appearance of a new plasmid in the transconjugants. In the case of pML31, we determined that this new plasmid was a recombinant composed of pNC21 and pML31, the latter flanked by two copies of transposable element Tn3. We believe that this recombinant plasmid was formed as an intermediate in the transposition of Tn3 from pNC21 to pML31 and was the vehicle for conjugational transmission of pML31 genes by a process known as plasmid conduction. PMID- 6247330 TI - Changes in cyclic nucleotide levels and dimorphic transition in Candida albicans. AB - The relationship between the levels of cyclic nucleotides and dimorphic transition in Candida albicans was examined. The results showed that cells of this pathogenic fungus contained both cyclic adenosine 3',5'-monophosphate (cAMP) and cyclic guanosine 3',5'-monophosphate (cGMP), the concentration of the latter being about one-tenth that of the former in stationary-phase cells of the yeast form. Our results further indicated that germ tube formation induced by incubation at 40 degrees C followed a rise in cAMP concentration in the cell with no accompanying change in cGMP content. Cysteine, which suppressed germination, also reversed the increase in intracellular cAMP concentration. Dibutyryl cAMP (1 MM) significantly promoted germination in proline medium at temperatures of 32 to 34 degrees C. These results suggested that cAMP was one of the controlling factors in the morphological transition in Candida albicans. PMID- 6247331 TI - Gene ilvY of Salmonella typhimurium. AB - Evidence is presented for the existence in Salmonella typhimurium LT2 of the regulatory gene ilv Y. The Escherichia coli K-12 ilvY gene product is shown to complement a S. typhimurium ilvY mutation in vivo. PMID- 6247333 TI - Permeability properties of Escherichia coli outer membrane containing, pore forming proteins: comparison between lambda receptor protein and porin for saccharide permeation. AB - Outer membrane permeability conferred by lambda receptor protein and porins to maltose-maltodextrins and other oligosaccharides was studied in vitro with reconstituted vesicle membranes and in vivo with mutant strains lacking either one of these proteins. The vesicle membranes reconstituted from phospholipids, lipopolysaccharide, and purified lambda receptor allowed rapid diffusion of maltose and maltose-maltodextrins of up to six glucose residues, but the membranes acted essentially as a molecular sieve for sucrose, raffinose, stachyose, and inulins of molecular weights 800, 920, and 1,380. The vesicle membranes containing porins allowed rapid diffusion of maltose but not of maltose maltodextrins larger than maltose. The apparent transport Km values for maltose maltodextrins of up to six glucose residues from the strain carrying lamB+ ompB (lambda receptor+, porin-) were similar (about 5 X 10(-6) M), whereas the transport Km values for maltose- and maltotriose of the strain carrying lamB ompB+ (lambda receptor-, porin+) alleles appeared to be 300 and about 20,000 X 10(-6) M. These results suggest that lambda receptor protein forms permeability pores that facilitate the diffusion of maltose-maltodextrins and function as a molecular sieve for other saccharides. PMID- 6247332 TI - Comparison of outer membrane porin proteins produced by Escherichia coli and Salmonella typhimurium. AB - The OmpC, OmpF, and Lc (NmpC) porin proteins of Escherichia coli K-12 have been shown to be similar to the OmpC (36K), OmpF (35K) and OmpD (34K) porin proteins of Salmnella typhimurium LT2 in terms of function, regulation of expression, and, in the case of OmpC and OmpF proteins, equivalence of the genetic loci determining their production. However, the corresponding pairs of proteins from these two species showed only limited similarity in peptide maps and no similarity in terms of migration on polyacrylamide gels. PMID- 6247334 TI - Recombination between bacteriophage lambda and plasmid pBR322 in Escherichia coli. AB - Recombinant lambda phages were isolated that resulted from recombination between the lambda genome and plasmid pBR322 in Escherichia coli, even though these deoxyribonucleic acids (DNAs) did not share extensive regions of homology. The characterization of these recombinant DNAs by heteroduplex analysis and restriction endonucleases is described. All but one of the recombinants appeared to have resulted from reciprocal recombination between a site on lambda DNA and a site on the plasmid. In general, there were two classes of recombinants. One class appeared to have resulted from recombination at the phage attachment site that probably resulted from lambda integration into secondary attachment sites on the plasmid. Seven different secondary attachment sites on pBR322 were found. The other class resulted from plasmid integration at other sites that were widely scattered on the lambda genome. For this second class of recombinants, more than one site on the plasmid could recombine with lambda DNA. Thus, the recombination did not appear to be site specific with respect to lambda or the plasmid. Possible mechanisms for generating these recombinants are discussed. PMID- 6247335 TI - Reconstitution of the Na+K+ pump of Ehrlich ascites tumor and enhancement of efficiency by quercetin. AB - Plasma membranes from Ehrlich ascites tumor cells were solubilized by octylglucoside in the presence of phospholipids. The Na+K+-ATPase was purified from this extract by adsorption and elution from thio-Seph-arose 4B. The enzyme (specific activity, 7 mumoles of ATP hydrolyzed min-1 mg of protein -1) was reconstituted into liposomes by the octyglucoside dilution procedure. An ATP dependent Na+ influx with low efficiency was observed. On addition of appropriate amounts of quercetin, the Na+ flux/ATP hydrolysis ratio was increased from 0.4 to 1.4. PMID- 6247336 TI - Cytochrome oxidase rotates in the inner membrane of intact mitochondria and submitochondrial particles. AB - A transient dichroism is detected after photolysis by a linearly polarized laser flash of the cytochrome oxidaseCO complex in bovine heart mitochondria, rat heart mitochondria, and bovine heart submitochondrial particles. A decay in the absorption anisotropy is characterized by a time constant of about 300 to 400 mus in both mitochondria and submitochondrial particles. Since vesicle tumbling in the time range less than 5 ms can be excluded in these experiments, we conclude that cytochrome oxidase rotates in the mitochondrial membrane with a relaxation time of several hundred microseconds. However, it is likely that only about one half of cytochrome oxidase contributes to the observed decay, the remainder being relatively immobile. PMID- 6247337 TI - Fluoride, pyrophosphate, and base release from 2'-deoxy-2'-fluoronucleoside 5' diphosphates by ribonucleoside-diphosphate reductase. AB - Ribonucleoside-diphsophate reductase from Escherichia coli catalyzes release of fluoride, inorganic pyrophosphate, and base from 2'-deoxy-2'-fluoronucleoside diphosphates. This reaction is accompanied by inactivation of the enzyme and an increase in absorbance at 314 nm of the inactivated protein. 2'-Deoxy-2' fluoroadenosine 5'-diphosphate requires two turnovers per inactivation, whereas 2'-deoxy-2'-fluorocytidine 5'-diphosphate requires 100 turnovers per inactivation. PMID- 6247338 TI - Purification of rat testicular microsomal 17-ketosteroid reductase. Evidence that 17-ketosteroid reductase and 17 beta-hydroxysteroid dehydrogenase are distinct enzymes. PMID- 6247340 TI - Amino acid sequence analysis of fragments generated by partial proteolysis from large simian virus 40 tumor antigen. AB - Large simian virus 40 tumor antigen was bound as immune complex to protein A Sepharose and then subjected to limited proteolysis which yielded several discrete fragments. Primary structures near the cleavage sites were determined by radiosequencing techniques. Experimental data for five fragments matched an amino acid sequence predicted from a nucleotide sequence at 0.51 map unit of the viral genome. We have thus identified the reading frame of translation beyond the intervening sequence at 0.60 to 0.53 map units. A cleavage map of tumor antigen was established on the basis of the sequence data and of the apparent molecular weights of the fragments. The bond most susceptible to cleavage by trypsin was between arginine-130 and lysine-131 in a cluster of five basis amino acids. Other cleavage sites were located in the COOH-terminal half of tumor antigen. Each fragment was analyzed by complete tryptic proteolysis and peptide mapping on an ion exchange column. Peaks occurring in the peptide map of large tumor antigen could thus be assigned to different segments of the protein. Two specific regions of tumor antigen were shown to be phosphorylated. PMID- 6247339 TI - Regulation of low density lipoprotein receptors by adrenocorticotropin in the adrenal gland of mice and rats in vivo. AB - Membranes prepared from the adrenal gland of mice and rats possess high affinity binding sites that recognize 125I-labeled human low density lipoprotein (LDL). These binding sites resemble the functional LDL receptors that mediate the uptake of LDL by cultured mouse and bovine adrenal cells. The number of LDL binding sites per mg of membrane protein increased 2- to 5-fold over 24 h when mice or rats were treated with adrenocorticotropin (ACTH). In rats, this increase was accompanied by a similar ACTH-induced increase in the adrenal uptake of intravenously administered 125I-LDL, suggesting that the LDL binding sites mediate the uptake of LDL by the adrenal in the intact animal. The number of LDL binding sites on adrenal membranes rose by 5-fold when animals were rendered lipoprotein-deficient, either by treatment of mice with 4-aminopyrazolopyrimidine or by treatment of rats with 17 alpha-ethinyl estradiol. This increase was prevented when endogenous ACTH secretion was blocked by administration of dexamethasone, suggesting that ACTH was required. The current experiments suggest that LDL receptors provide one source of cholesterol for the mouse and rat adrenal in vivo and that the number of LDL receptors of this organ is regulated by ACTH. PMID- 6247341 TI - Actin deoxyroboncuclease I interaction. Depolymerization and nucleotide exchange. AB - Deoxyribonuclease I (DNase I) forms a 1:1 complex with globular actin (G-actin) and also will depolymerize filamentous actin (F-actin) to form a 1:1 complex. The effect of DNase I on the exchange of the actin nucleotide has been investigated. When DNase I is added to G-actin, the rate of nucleotide exchange is decreased from 1.16 +/- 0.25 X 10(-4) s-1 to 0.28 +/- 0.09 X 10(-4) s-1 (0 degrees C). The presence of ATP or ADP in the actin has little effect on the rate of exchange of the nucleotide for ATP. This suggests that the weaker affinity of ADP than ATP for actin is due to a slower association rate of ADP. The rate of the nucleotide exchange in the actinDNase I complex is increased by the addition of NaCl or MgCl2. When DNase I is added to F-actin, the rate of nucleotide exchange (6.2 +/- 1.6 X 10(-4) x-1, 0 degrees C) is similar to the rate of depolymerization as measured by loss of viscosity. The actinDNase I complex formed by depolymerization of F-actin exchanges nucleotide at a 4-fold faster rate than the G-actinDNase I complex in the same ionic conditions. This and other experiments suggest that DNase I binds first to F-actin before dissociating the monomer from the filament. These results are discussed in terms of possible mechanisms of action depolymerization. PMID- 6247342 TI - Metabolism of fatty acids by cultured tumor cells and their diploid precursor fibroblasts. PMID- 6247343 TI - Inhibition by vanadate of the reactions catalyzed by the (Na+ + K+)-stimulated ATPase. A transient state kinetic characterization. AB - The interaction of vanadate with the (Na+ + K+)-stimulated ATPase from electric organ was investigated using the acid quench-flow technique. At 21 degrees C, incubation of the enzyme with 1.3 to 1.6 muM vanadate in the presence of 75 mM Na+ and 25 mM K+ strongly inhibits phosphorylation by ATP. Enzyme activity remaining under these conditions shows no change in the apparent rates of phosphorylation or dephosphorylation, although effects were noted which suggest that vanadate increases the reverse rate of dephosphorylation. Ten micromolar vanadate, sufficient to inhibit the (Na+ + K+)-stimulated ATPase by more than 98%, has no effect on phosphorylation in the presence of Na+ alone. Phosphoenzyme formed in the presence of Na+ and K+ consists of rapidly and slowly decaying components which differ in sensitivity to vanadate. Up to 2 muM vanadate suppresses predominantly the rapidly decaying phosphoenzyme, while at higher concentrations vanadate inhibits both the rate and level of formation of the slowly decaying phosphoenzyme. These results indicate that vanadate is a useful reagent for distinguishing between these two phosphorylation reactions. PMID- 6247344 TI - Are polyphosphoinositides the cycloheximide-sensitive mediator in the steroidogenic actions of adrenocorticotropin and adenosine-3',5'-monophosphate? PMID- 6247345 TI - The isolation and partial characterization of two substrate-specific protein activators of the reticulocyte phosphoprotein phosphatase. PMID- 6247346 TI - Interaction of Mn2+ and MnATP2- with the allosteric sites of AMP nucleosidase. PMID- 6247347 TI - Effect of cholesterol concentration on organization of viral and vesicle membranes. Probed by accessibility to cholesterol oxidase. PMID- 6247348 TI - Isolation and properties of an NAD- and guanidine-dependent ADP ribosyltransferase from turkey erythrocytes. AB - An NAD- and guanidine-dependent ADP-ribosyltransferase has been purified more than 500,000-fold from turkey erythrocytes with an 18% yield. The enzyme in the 100,000 X g supernatant fraction was bound to phenyl-Sepharose, eluted with 50% propylene glycol, and further purified by sequential chromatographic steps on carboxymethylcellulose, NAD-agarose and concanavalin A-agarose. The transferase was specifically eluted from concanavalin A-agarose with alpha-methylmannoside. The enzymatic activity was extremely labile following the first purification step. Both propylene glycol and NaCl stabilized the transferase; significant increases in enzyme recovery were obtained by conducting the NAD- and concanavalin A-agarose chromatography in buffer containing propylene glycol. The purified protein exhibits one predominant protein band on SDS-polyacrylamide gels with an estimated molecular weight of 28,300. On Ultrogel AcA54 chromatography, single coincident peaks of ADP-ribosyltransferase activity and protein were observed. Enzyme activity was independent of DNA; the highly purified transferase was inhibited by thymidine, nicotinamide, and theophylline. The specific activity of the purified enzyme (350 mumol of ADP-ribose transferred from NAD to arginine methyl estermin-1mg-1) is comparable to that reported for purified NAD glycohydrolases and poly(ADP-ribosyl)transferases. PMID- 6247349 TI - Effects of trypsin on binding of [3H]epinephrine and [3H]-dihydroergocryptine to rat liver plasma membranes. Evidence for interconversion of binding sites. AB - Treatment of liver plasma membranes with trypsin at low concentrations (1 to 2 microgram/mg of protein) caused at 3- to 4-fold increase in alpha-specific [3H]epinephrine binding. The change was due to an increase in the number of high affinity binding sites, with no change in the dissociation constant. With increasing trypsin concentrations, the dissociation constant was decreased and there was a progressive loss of binding. Elastase, papain, and thermolysin caused similar effects, whereas the thrombin, leucine aminopeptidase, phospholipase A2, phospholipase C, phospholipase D, and detergents did not cause an increase in [EH]epinephrine binding. The increase in epinephrine high affinity binding sites was correlated with a loss of high affinity [3H]-dihydroergocryptine binding sites which also bind [3H]epinephrine with low affinity (El-Refai, M. F., Blackmore, P. F., and Exton, J. H. (1979) J. Biol. Chem. 254, 4375-4386). Incubation of membranes with the alpha blockers dihydroergocryptine (50 nM) and phenoxybenzamine (20 nM) prior to protease treatment diminished the increase in [3H]epinephrine binding induced by trypsin (1.5 microgram/mg). The concentration dependence and time course of trypsin actions on 70 nM [3H]epinephrine binding and 10 nM [3H]dihydroergocryptine binding are consistent with a trypsin-mediated conversion of low affinity epinephrine binding sites to high affinity epinephrine binding sites. PMID- 6247350 TI - Cyanide binding to the cytochrome c ferric heme octapeptide. A model for anion binding to the active site of high spin ferric heme proteins. AB - Equilibrium constants for the binding of cyanide to the ferric heme c octapeptide in 20% ethylene glycol, 50% buffer were measured spectrophotometrically. The equilibrium constant for cyanide binding at 20 degrees C and pH 7.4 is 3.47 X 10(7), which is approximately 15-fold lower than that observed for cyanide binding to methemoglobin or metmyoglobin. Equilibrium constants at several temperatures exhibited an apparent van't Hoff relationship, yielding thermodynamic values of delta H degrees = -79,000 J/mol (-18,900 cal/mol) and delta S degrees = J/degrees K mol (-30.1 e.u.). Comparison of the ratio of equilibrium constants for cyanide ligation to methemoglobin the heme octapeptide with the ratio of equilibrium constants for azide ligation to methemoglobin and the heme octapeptide suggests that cyanide binding to the methemoproteins is much smaller than expected by comparison to azide binding. The differences in the ratios, the thermodynamic values, and the preferred binding geometries suggest that CN- ligation, like CO ligation, is sterically hindered. A comparison of these ratios to similar ratios for CO, O2, and NO binding suggests that the Fe-CN bond angle is less subject to distortion than the Fe-CO bond and/or additional binding interactions contribute to N3- but not to CN-binding to the protein. PMID- 6247351 TI - Stability differences between high coagulant (alpha) and noncoagulant (gamma) human thrombins. Denaturation. AB - Human alpha-thrombin, the two (covalently linked)-chain, highly coagulant blood clotting enzyme was compared with its noncoagulant, yet estero/amidolytically active derivative, gamma-thrombin, a three (noncovalently associated)-domain enzyme which results from two proteolytic cleavages of the coagulant a form. Studies of their denaturation behavior by Tos-Arg-OMe esterase activity, by intrinsic fluorescence, by fluorescence of active serine-directed dansyl labels, and by monitoring the ESR of a fluorosulfonylphenyl spin-labeled inhibitor clearly demonstrated the reduced stability of the noncovalently associated gamma thrombin form. At pH 6.5, 0.75 M NaCl, gamma-thrombin unfolds in approximately 2. 1 M urea while the more stable a form denatures at approximately 4 M urea. By monitoring active serine probes (spin label or fluorescent labels), these transitions were slightly lower, 1.0 +/- 0.1 and 2.8 +/- 0.2 M urea for spin labeled gamma- and alpha-thrombins, respectively. Similar behavior was found for the same spin-labeled derivatives in guanidine HCl with unfolding transitions of 0.4 M and 1.0 M for spin-labeled gamma- and alpha-thrombin, respectively. These differences in structural stabilization serve as a good physical diagnostic for the two thrombin species. PMID- 6247352 TI - Multifunctional glucose-6-phosphatase studied in permeable isolated hepatocytes. PMID- 6247353 TI - Purification and properties of bovine brain calmodulin-dependent cyclic nucleotide phosphodiesterase. AB - Calmodulin-dependent cyclic nucleotide phosphodiesterase was purified from bovine brain to apparent homogeneity by a new procedure involving DEAE-cellulose, Affi Gel blue, calmodulin-Sepharose 4B, and Sephadex G-200 column chromatographies. The enzyme was purified more than 3,000-fold from the brain extracts with greater than 12% yield. The purified phosphodiesterase could be activated 10- to 15-fold by calmodulin and Ca2+ to a specific enzyme activity of more than 300 mumol of cAMP hydrolyzed/min/mg of protein. Molecular weight of the enzyme was determined to be 115,800 by the sedimentation equilibirum method or 124,000 from the sedimentation constant and Stokes radius of the protein. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of the enzyme showed a single protein band with an apparent molecular weight of 58,000. These results suggested that the calmodulin-dependent phosphodiesterase from bovine brain has a subunit structure of alpha2. Molecular weight of the complex of calmodulin and phosphodiesterase was the complex of calmodulin and phosphodiesterase was also calculated from the sedimentation constant and Stokes radius to be 159,000. Since calmodulin has a molecular weight of about 17,000, the result indicated that the stoichiometry of the complex is calmodulin2 alpha2. The catalytic subunit of cylic AMP-dependent protein kinase was found to catalyze the phosphorylation of the purified phosphodiesterase with the incorporation of 2 mol of phosphate/mol of the enzyme. PMID- 6247354 TI - Reconstituted G protein-lipid vesicles from vesicular stomatitis virus and their inhibition of VSV infection. AB - The single glycoprotein (G) of vesiclar stomatitis virus (VSV) was isolated in nearly quantitative yield by extraction of the purified virions with 0.05 M octyl beta-D- glucoside (OG) in 0.01 M sodium phosphate, pH 8.0. The extract contained essentially all of the viral phospholipids and glycolipids, and was free of other essentially all of the viral phospholipids and glycolipids, and was free of other viral proteins. Dialysis to remove OG resulted in the formation of G protein viral lipid vesicles having a lipid-G protein ratio similar to that of the intact virions. The vesicles were 250-1,000 A in diameter, with a "fuzzy" external layer also similar to that of intact virions. The vesicles were predominantly unilamellar and sealed, with both phosphatidyl ethanolamine and gangliosides symmetrically distributed in the bilayer. G protein was asymmetrically oriented, with about 80 percent accessible to exogenous protease. Addition of soybean phospholipid to the viral extract before dialysis resulted in vesicles that incorporated viral proteins and lipids quantitatively, but that were markedly decreased in buoyant density. The G neutralized protein-lipid vesicles were effective in eliciting specific anti-G antibodies that neutralized viral infectivity. Competitive radioimmunoassay showed that both reconstituted vesicles and a soluble form of G protein (Gs) were indistinguishable from purified VSV in their antibody binding properties. Addition of G protein-lipid vesicles of BHK-21 cells before, or simultaneously with, infection by VSV inhibited viral infectivity, as measured by two independent techniques (viral RNA production in the presence of actinomycin D and a neutral red assay of cell viability). The total inhibitory activity of G protein in the vesicular form was, however, less than 5 percent of that found for intact virus particles that have been inactivated by ultraviolet light irradiation. Gs was inactive as an inhibitor as determined by the RNA production assay. PMID- 6247355 TI - Inhibition of vesicular stomatitis virus infection by spike glycoprotein. Evidence for an intracellular, G protein-requiring step. AB - In an assay measuring virus-directed RNA synthesis, infection of BHK cells by a standard test dose of vesicular stomatitis virus (VSV) was inhibited by ultraviolet light-irradiated wt VSV and by ts 045, one of a number of thermolabile, temperature-sensitive G protein mutants of VSV. After heat treatment for 1 h at 45 degrees C, the thermolabile mutants were no longer able to inhibit the VSV infection. In contrast, the thermolabile M protein mutant ts G31 and the nonthermolabile G protein mutant ts 044 could still inhibit the test VSV dose. Thus, the presence of G protein in its native conformation was necessary for inhibition of infection. There was little difference in the binding to cells or the internalization to a trypsin-resistant state of ts 045 or wt VSV before and after heat treatment, and there was no evidence of specific saturable receptors on the cell surface. None of the irradiated virions at concentrations that gave maximal inhibition of infection could prevent binding of infectious VSV to, or internalization by, BHK cells. The G protein-specific inhibition, therefore, did not occur at the cell surface but must have occurred at some intracellular site, which has been suggested to be the lysome. The lysosomal inhibitor chloroquine, when added with the infecting virus, completely inhibited VSV infection at all multiplicities of infection tested, and it gave 50% inhibition when added to 1.5 h after infection. The possible importance of the lysosome in the intracellular pathway of infection is discussed. PMID- 6247356 TI - [Primary linitis plastica of the rectum (author's transl)]. AB - One case of primary linitis plastica of the rectum is presented, adding to the 20 previous cases reported in the literature, the diagnosis was made aften excluding the stomach as a primary source by per operative palpation and radiographic examination. Absence of blood in the stools and predominant symptomatology of diarrhea explains the delay of diagnosis in this patient with chorea. About 20% of all reported cases occur in association with ulcerative colitis. The prognosis is poor; the maximal survival reported is 2 1/2 years; the mean survival time is about 4 months. PMID- 6247357 TI - Two-dimensional thin-layer chromatography of Dns-amino acids on reversed-phase silica gel. AB - Ready-for-use reversed-phase high-performance thin-layer chromatographic plates were used for the separation of Dns-amino acids. The development was performed by using methanol-2% acetic acid (75.25) or methanol-0.01 M Na2HPO4 (75:25). Reversed-phase plates were used also for adsorption chromatography using a non aqueous solvent system such as benzene-chloroform-acetic acid (50:48:2) or n heptane-ethyl acetate-acetic acid (65:33:2). Good separations were achieved by using both principles in the two-dimensional arrangement. PMID- 6247358 TI - Application of a sintered silica gel plate to the thin-layer chromatography of carbohydrates. PMID- 6247359 TI - Solubilized nuclear thyroid hormone receptors in circulating human mononuclear cells. AB - In order to assess iodothyronine receptor interactions in man, we have developed a receptor assay for T3 and T4 in solubilized nuclear extracts from circulating mononuclear cells. This assay utilizes the technique of salt solubilization to isolate nuclear receptors and employs standard saturation analysis for T3 and T4 to determine maximal binding capacity (MBC) and equilibrium dissociation constants (Kd). We have determined that 11 normal subjects had a MBC for T3 of 1.20 +/- 0.20 pmol/mg DNA (+/- SE) and a Kd of 3.4 +/- 0.2 X 10(-10) M; the T4 MBC was 8.44 +/- 1.22 pmol/mg DNA and the Kd was 2.7 +/- 0.3 X 10(-10) M. Hypothyroid patients had a mean T3 MBC of 7.32 +/- 2.28 pmol/mg DNA and a mean T4 MBC of 40.04 +/- 21.36 pmol/mg DNA (P less than 0.05 compared to normal). Obese subjects (n = 12) had a basal fed MBC that was 0.66 +/- 0.13 pmol/mg DNA for T3 (P less than 0.05 compared to normal) and was 3.58 +/- 0.56 pmol/mg DNA for T4 (P less than 0.01 compared to normal). During fasting, the average T3 MBC increased to 1.43 +/- 0.31 pmol/mg DNA and the average T4 MBC increased to 9.63 +/- 2.46 pmol/mg DNA, values that are both significantly higher than those in the fed period; the dissociation constants were unaltered in obese subjects (compared to normals) in fed and fasting states. Gel filtration with 0.5 M agarose was employed to ascertain if the physicochemical properties of the solubilized mononuclear human cell receptor were similar to those previously observed in rat and human liver and kidney receptors. The elution profile obtained was similar to that reported earlier. The major binding activity has an estimated Stokes radius of 35 A and a molecular weight ratio of approximately 50,000 daltons. These studies indicate that: 1) high affinity T3 and T4 receptors exist in human mononuclear cells and have properties similar to those for T3 and T4 described previously in rat liver; 2) T3 and T4 receptor number tends to increase in hypothyroid subjects and tend to be lower in obese patients than in normal weight control subjects; 3) fasting is associated with an increase in both T3 and T4 MBC; and 4) despite their apparent physicochemical similarity, T3 receptors in rat liver and human mononuclear cells may be regulated differently, at least during fasting since hepatic T3 receptors decrease in the fasted rat. Collectively, these observations support the concept that human white cell T3 nuclear receptor binding is capable of rapid fluctuations, suggesting a mechanism for homeostatic regulation of T3 action. PMID- 6247360 TI - Elevated nephrogenous cyclic AMP with normal serum parathyroid hormone levels in patients with lung cancer. AB - Total and nephrogenous urinary cyclic AMP (cAMP), serum Parathyroid Hormone (PTH) and ionized calcium (Ca) levels were determined in 8 normal subjects, and 16 normocalcemic and 9 hypercalcemic patients with lung cancer. Total and nephrogeneous cAMP levels were significantly increased in both normocalcemic and hypercalcemic lung cancer patients, as compared to normal subjects. There was no significant correlation between serum PTH and total or nephrogenous cAMP in the cancer group. The factors responsible for the elevated nephrogenous cAMP in the lung cancer patients are not known. PMID- 6247361 TI - Simulation of the normal menstrual cycle in Kallman's syndrome by pulsatile administration of luteinizing hormone-releasing hormone (LHRH). AB - The administration of small doses of LHRH at 2-hourly intervals over a 27 day period to a 24-year old patient with Kallman's syndrome resulted in ovulation as indicated by: (1) a biphasic temperature response, (2) anatomical changes in the ovaries demonstrated by ultrasound, and (3) the pattern of circulating gonadotropin and gonadal steroid concentrations. PMID- 6247362 TI - In vitro steroidogenic properties of a new hypertension-producing compound isolated from normal human urine. AB - The steroidogenic properties of a glycoprotein fraction (ASF), isolated from normal human urine, were studied in cat adrenal capsular collagenase-dispersed cells and its effects compared to those of ACTH and Angiotensin II (AII). ACTH, AII and ASF induced dose-related increases in both aldosterone and cortisol production. In order of potency, ACTH = AII greater than ASF in stimulating aldosterone production and ACTH greater than AII greater than ASF in stimulating cortisol production. Increases in cAMP accompanied the steroidogenic response to ACTH but not to AII or ASF. The response to AII, but not to ASF, was inhibited (87% of normal) by equimolar concentrations of [Sar1, Thr8]AII, a specific AII antagonist. These results suggest that ASF is a true aldosterone secretagogue and that it initiates steroidogenesis by mechanisms similar to those of AII. However, the inability to block it effect with a specific antagonist of AII provides evidence for its action on a separate receptor site. PMID- 6247363 TI - Evidence for a peptide similar to 16K fragment in man. Its relationship to ACTH. AB - A radioimmunoassay directed toward the NH2-terminal region of mouse pro ACTH/endorphin (called 16K fragment) was used to examine human samples. Culture media from two corticotropic adenomas and plasmas from 11 patients with various ACTH hypersecretory syndromes gave parallel displacement curves; displacement curves for human samples were not parallel to purified mouse 16K fragment. Following sodium dodecyl sulfate polyacrylamide gel electrophoresis of culture medium from one adenoma, a major peak of 16K fragment immunoreactivity with an apparent molecular weight of ca. 16,000 was detected. A significant correlation (r = 0.963 ; p less than 0.001) was found between immunoreactive 16K fragment and ACTH in the patients' plasmas. These data indicate that a peptide similar to 16K fragment exists in man ; that human and mouse 16K fragment are immunologically distinguishable and that human 16K fragment appears to be secreted concomitantly with ACTH. PMID- 6247364 TI - Prostaglandin-mediated stimulation of adenosine 3',5'-monophosphate accumulation and parathyroid hormone release in dispersed human parathyroid cells. AB - Freshly dispersed cells were employed to study the effects of various prostaglandins (PGs) on cAMP accumulation and parathyroid hormone release in abnormal human parathyroid tissue. PGE1 and PGE2 effected dramatic increases in intracellular cAMP accumulation over a concentration range of 10(-6)-10(-4) M; the relative effectiveness of these agents varied among different preparations. PGF2 alpha caused a smaller stimulation of cAMP accumulation, and PGF1 alpha was generally without effect. In contrast with the effect previously described in the bovine parathyroid cell system, PGF2 alpha did not suppress agonist-stimulated cAMP accumulation. Both PGE1 and PGE2 enhanced cellular release of parathyroid hormone, with dose-response characteristics similar to those seen with cAMP. In addition, both agents led to a significant stimulation of adenylate cyclase activity in a cellular homogenate preparation. Neither indomethacin (10(-5) M) nor naproxen (10(-4) M) altered the calcium suppressibility of the cells, suggesting that endogenous PG production does not play a major role in the calcium-mediated regulation of parathyroid hormone release. PMID- 6247365 TI - Adenosine 3',5'-monophosphate concentrations and responsiveness to thyrotropin and thyroid-stimulating immunoglobulins in normal and Graves' thyroids. PMID- 6247366 TI - Indirect hemagglutination test for pseudorabies antibody detection in swine. AB - An indirect hemagglutination test for the detection of antibodies in swine serum specific for pseudorabies virus is described. The indirect hemagglutination test was less time consuming than the standardized virus nertralization test while being highly sensitive and accurate. Serum samples that were toxic to virus neutralization indicator cells were readily tested in the indirect hemagglutination test. The indirect hemagglutination test may also be more sensitive than the virus neutralization test for determining early titers in pseudorabies virus infections. Complete methodology is described. PMID- 6247367 TI - Latex test for serodiagnosis of infectious mononucleosis. AB - A glycoprotein was isolated from bovine erythrocytes which has 20% carbohydrate and migrates on sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a single band. This glycoprotein carries the reactivity of bovine erythrocytes with Paul-Bunnell heterophile antibody of infectious mononucleosis. This bovine glycoprotein was coupled to carboxyl-modified latex particles with water-soluble carbodiimide. The resulting reagent was then used to develop a new test for the detection of infectious mononucleosis antibody. The bovine erythrocyte glycoprotein-latex reagent is more stable than sheep or horse erythrocytes, the traditional reagents for detection of infectious mononucleosis antibody. This new reagent is used in a direct slide test; no preabsorption of the sera is necessary. In the present study the glycoprotein-latex reagent compared favorably in terms of sensitivity and specificity with two standard tests for infectious mononucleosis antibody. Ninety-nine serum samples were tested. Agreement of the latex test with a stabilized horse erythrocyte spot test was 90%. Ten samples were weakly positive with the latex test and negative with the horse cell test. Only one of these was also positive with an enzyme-treated sheep cell test. This latter test was somewhate more sensitive than the latex test. PMID- 6247368 TI - Seroepidemiology of rotavirus infection in rural Bangladesh. AB - A prospective seroepidemiological study of rotavirus infection was performed in children in a village in rural Bangladesh. Ninety-three percent of the children had detectable antibodies during the study, and there were 66 significant rises in titer occurring in 57 of the 85 children. Antibody titer rises occurred in older children and younger children with equal frequency. Nine children (11%) had evidence of multiple infections during the 16-month period. Winter infections were most frequent, although one summer (monsoon) season was also associated with a large cluster. Subjects with high titers (greater than 1:8) of antibody less frequently developed a titer rise than did subjects with lower titers. PMID- 6247369 TI - Parainfluenza virus isolation enhancement utilizing a portable cell culture system in the field. AB - Using a portable minaturized cell culture system, enhanced recoveries of parainfluenza virus types 1 and 3 were made in the field from symptomatic human adult subjects working at remote Antarctic stations. PMID- 6247370 TI - An outbreak of rotavirus infection in a long-stay ward of a geriatric hospital. AB - An outbreak of rotavirus infection in elderly patients in a long-stay ward of a geriatric hospital is described. Virus was detected in 7/15 (47%) symptomatic individuals. Four members of staff were among those affected. The findings emphasise the need for electron microscopy to be used in the initial investigation of outbreaks of diarrhoea in all age groups. PMID- 6247371 TI - Evaluation of the analgesic properties of zomepirac. AB - Zomepirac, an inhibitor of prostaglandin biosynthesis, was evaluated for analgesic activity in a number of pharmacological screens. In the acetylcholine writhing test, zomepirac was found to be more potent than codeine, pentazocine, aspirin, and acetaminophen and equivalent in potency to morphine. Zomepirac was inactive in a number of tests that detect narcotic agents, suggesting that the drug will not induce physical dependence. The possibility of a central nonnarcotic as well as a peripheral analgesic mechanism merits consideration. PMID- 6247372 TI - Temperature effects on cyclic AMP accumulation in cultured fibroblasts. AB - The kinetic parameters that determine the accumulation of cAMP in WI-38 cells stimulated with prostaglandin E1 have been determined at 37 degrees C and at lower temperatures. For desensitized cells, a reduction of temperatures from 37 degrees to 25 degrees C reduced both rate of synthesis and rate of elimination of cAMP by about 40%. The steady-state accumulation was, therefore, about the same at both temperatures. The extent of desensitization was also shown to be comparable at the two temperatures. It can be inferred that there was appreciable desensitization at 4 degrees C after a period of stimulation of less than one hour. This is contrasted with the behavior of C6-2B glioma cells at the same temperature. Escape of cAMP through the plasma membrane showed a greater temperature dependence than any of the other processes concerned with cAMP accumulation. PMID- 6247373 TI - Phosphatidic acid inhibition of PGE1-stimulated cAMP accumulation in WI-38 fibroblasts: similarities with carbachol inhibition. AB - To test the hypothesis that phosphatidic acid (PhA) is involved in the carbachol inhibition of hormone stimulated accumulation of cAMP we observed the effects of PhA on PGE1-stimulation of cAMP in WI-38 fibroblasts. PhA inhibited PGE1 stimulated cAMP accumulation of WI-38 fibroblasts; maximum inhibition (approximately 50-80%) occurred at a PhA concentration of 1.0 microM and significant inhibition was observed with a concentration of 0.1 microM. The full effects of PhA were evident within 15 sec after the co-addition of PGE1 and PhA. Addition of PhA to cells which had been pre-stimulated with PGE1 resulted in the rapid decay of cAMP levels to a new steady state level with a t 1/2 of approximately 65 sec. The inhibition produced by PhA did not appear to be simply attributable to a depolarization or increased intracellular Ca2+, since addition of either KCl or the Ca2+ ionophore A23187 did not lower PGE1-stimulated cAMP accumulation. When intact cells were pretreated with PhA then lysed and adenylate cyclase immediately assayed, no detectable changes in broken cell adenylate cyclase activities were observed. Also, PhA added directly to adenylate cyclase assays at concentrations as high as 100 microM produced no detectable inhibition of the membrane fraction adenylate cyclase activities. Nonetheless, our results suggest that adenylate cyclase activity in intact cells may be directly affected by physiological levels of PhA . Further, the similarities of carbachol [Butcher, R. W., Journal of Cyclic Nucleotide Research, 4:411 (1978)] and PhA inhibition support the hypothesis that carbachol (acetylcholine) exerts its effect on adenylate cyclase through alterations of the plasma membrane phospholipid composition. PMID- 6247374 TI - Alcohol potentiation of isoproterenol-stimulated cyclic AMP accumulation in rat parotid. AB - The ability of beta-adrenergic agonists to elevate rat parotid cyclic AMP concentrations is potentiated greatly by certain organic solvents. Propanol was found to be more effective than other tested solvents. Propanol stimulated adenylate cyclase and inhibited low Km cyclic AMP phosphodiesterase activities however the magnitude of effect upon these enzyme activities probably does not account for the potentiation of cyclic AMP accumulation observed in intact cells. PMID- 6247376 TI - Cyclic AMP level in different layers of psoriatic epidermis. PMID- 6247375 TI - Immunoglobulin absorption in calf neonates with special considerations of stress. AB - The concept that hyperadrenalemia resulting from stress may suppress colostral immunoglobulin absorption or terminate intestinal permeability in the bovine neonate has not been substantiated by objective research. Experiments with exogenous corticosteroids or induction of endogenous secretion of the adrenals have not demonstrated the same effect as in rodents where precocious maturation of intestinal epithelium terminates macromolecular protein absorption. Evidence is given that certain prepartum stressors on the dam may influence colostral immunoglobulin absorption in the calf. High environmental temperature influences colostral immunoglobulin absorption. PMID- 6247377 TI - Dental research developments reported at AADR meeting. PMID- 6247378 TI - Is a mast cell a mast cell a mast cell? PMID- 6247380 TI - Abnormal beta adrenergic responsiveness in allergic subjects: analysis of isoproterenol-induced cardiovascular and plasma cyclic adenosine monophosphate responses. PMID- 6247379 TI - Characterization of granulocyte beta adrenergic receptors in atopic eczema. AB - The binding of (-)-3H-dihydroalprenolol (3H-DHA) and 125I-hydroxybenzylpindolol (125I-HYP) to the beta-adrenergic receptors in homogenized granulocyte preparations from control subjects and patients with atopic eczema was characterized. No difference was found for the affinity (KD=2 X 10(-9) M) or the total number of high-affinity binding sites (1,200 to 1,600 per cell) with 3H-DHA or 125I-HYP (KD 1.6 X 10(-10) M) in granulocytes from the two study populations. Scatchard plots of the data obtained from DHA binding isotherms suggested that negative cooperativity may exist as a property of the beta 2-receptor. Granulocyte preparations from control subjects and patients with atopic eczema also showed propranolol protectable 3H-DHA binding with a KD of 10(-7) M. It is not clear whether these 3H-DHA binding sites represent physiologically significant beta-adrenergic receptors at these concentrations of radioligand. It was found that 15,000 to 20,000 binding sites of this lower affinity for DHA exist per cell in granulocytes from the two populations of subjects. These data suggest that the reduced isoproterenol responsiveness of granulocytes from patients with atopic eczema is not the result of abnormal or reduced numbers of beta-adrenergic receptors. PMID- 6247382 TI - Psychological soundness of women on psychiatry clerkship. PMID- 6247381 TI - Platelet aggregability in 101 patients with atherothrombotic ischemic cerebral disease. PMID- 6247383 TI - Employment and fertility among married women. PMID- 6247384 TI - On the history of JAMWA. PMID- 6247385 TI - Twenty years of funding of research by the National Institute of Health grant 02904 entitled "Determination of Natural Clotting Factors". PMID- 6247386 TI - Setting up a rape treatment center. PMID- 6247387 TI - Women's health issues. PMID- 6247388 TI - Synovial sarcoma. A review and pedal presentation. PMID- 6247389 TI - Synovial sarcoma of the tibialis posterior tendon. A case report. PMID- 6247390 TI - The ultracytochemical localization of cytidine-5'-monophosphatase in normal human thyroid follicle cells. AB - The properties and distribution of an enzyme specifically hydrolyzing cytidine-5' monophosphate and the possible relationship of the enzyme to the synthesis and secretion of thyroid hormone in man were investigated using cytochemical methods. Activity due to cytidine-5'-monophosphatase was separated from that due to acid or alkaline phosphatase, both of which are also capable of hydrolyzing cytidine 5'-monophosphate. This distinction was established on the basis of manganese ion stimulation and differences in localization, levels of activity, and pH optimums. The localization of the enzyme along the face of Golgi apparatus involved in the formation of thyroglobulin suggests an association of the enzyme with the glycosylation of thyroglobulin. PMID- 6247391 TI - Alkaline phosphatase and an acid arylamidase as marker enzymes for normal and transformed WI-38 cells. AB - A survey of eleven enzyme activity levels in normal and SV40 transformed (VA-13) WI-38 cells revealed that the transformed cell enzymes differed by a quantitative and qualitative change of alkaline phosphatase and a quantitative loss of an arylamidase. Alkaline phosphatase activity was found to be elevated in the transformed cells at confluency but not in log phase cultures. This elevated activity was heat stable, L-homoarginine resistant and L-phenylalanine sensitive and is probably the term placental isoenzyme. In nontransformed WI-38 cells, the alkaline phosphatase was heat labile, L-homoarginine sensitive and L phenylalanine resistant and so is probably the liver isoenzyme. While the arylamidase activity from both normal and transformed WI-38 cells had identical pH optima and Km values, the activity was approximately 20 times higher in confluent WI-38 cells than in confluent VA-13 cells. Cytochemical staining techniques for both activities are described that permit identification of fluorescent product within the cells, analysis of activity levels, and separation of cells with high and low activities. Mixtures of WI-38 cells and VA-13 cells separated by flow cytometry on the basis of arylamidase activity were subsequently evaluated for alkaline phosphatase isoenzyme and found to have been simultaneously separated into heat labile and heat stable samples. PMID- 6247392 TI - [Ultrastrastructural and histochemical examinations of afferent pathways of the geniculate-cortical relay cells]. AB - On the basis of ultrastructural and ultrahistochemical studies in the dorsal part of lateral geniculate nucleus (d LGN) of albino rat a topistical model of geniculo-cortical relay cell (GCR-cell) afferentiation is proposed. Retinal afferent terminals of type 2a and 2b and their synaptic properties are discussed in connection with slow and fast conducting retinofugal channels. Interneuronal contacts are represented by presynaptic dendritic specializations (P-bouton) and by axonal terminals (F-bouton) (LIEBERMAN and WEBSTER, 1974). These findings suggest that the function of interneurons may be dualistic. Cortical afferents are represented by small terminals with round agranular vesicles. Using the "false" transmitter 5-OH-DA we succeeded in demonstrating degenerating terminals with dense core vesicles. There is evidence that noradrenergic axons originating in the Locus coeruleus may contact with the distal dendritic parts of GCR neurons. PMID- 6247393 TI - Ecto-5'-nucleotidase activity in lymphoblastoid cell lines derived from heterozygotes for congenital X-linked agammaglobulinemia. AB - Lymphoblastoid cell lines were established from female relatives of patients with congenital X-linked-agammaglobulinemia by Epstein-Barr virus transformation of their peripheral B lymphocytes. Cell lines derived from presumed carriers were characterized by low ecto-5'-nucleotidase activity and a reduced percentage of surface immunoglobulin-bearing cells. Measurement of ecto-5'-nucleotidase activity in newly established lymphoblastoid cell lines may provide a means for the identification of heterozygotes for congenital X-linked agammaglobulinemia. PMID- 6247394 TI - EBV-transformation of surface IgA-positive human lymphocytes. AB - Surface IgA-positive human lymphocytes were selected, separated, and immortalized with Epstein-Barr virus (EBV). Selection was carried out by rosetting the cells with ox erythrocytes, coated with rabbit anti-human IgA immunoglobulin, followed by separation on Ficoll-Isopaque. Stable monoclonal lines were established by cloning in agarose. This shows that EBV-transformation is not restricted to the IgM-positive B cell category but can be extended to minority classes of B lymphocytes. The method provides the means to establish other minority categories as continuous lines, depending on the efficiency of the preselection procedure. PMID- 6247395 TI - Delayed hypersensitivity in mice infected with reovirus. I. Identification of host and viral gene products responsible for the immune response. AB - Delayed-type hypersensitivity (DTH) can be demonstrated in mice infected with reovirus by challenging primed animals in the footpad with virus. Maximal responses occur 7 days after immunization with as little as 10(5) viral particles. DTH to reovirus is transferable by lymph node cells and is mediated by T cells as the transfer of reactivity can be abrogated by treatment of cells with anti-Thy 1.2 plus complement. DTH to reovirus is serotype specific, animals infected with reovirus type 1 or 3 only develop DTH responses when challenged with the same serotype with which they were infected. Using recombinant viral clones containing genes from both parental serotypes, we have demonstrated that the S1 gene, the gene encoding the viral hemagglutinin, determines serotype specificity. Furthermore, in adoptive transfer experiments between mice of varying histocompatibility backgrounds, it was found that D or K, IA-IB region identity was required for the transfer of reactivity. These studies demonstrate that specific host and viral genes determine the in vivo cellular immune response to reovirus and should allow a more precise definition of the host cellular immune response to viral antigens. PMID- 6247396 TI - Delayed hypersensitivity in mice infected with reovirus. II. Induction of tolerance and suppressor T cells to viral specific gene products. PMID- 6247397 TI - Vesicular stomatitis antigens recognized by cytotoxic cells: analysis with defective interfering particles and reconstituted membrane vesicles. PMID- 6247398 TI - A comparison of the superoxide-releasing response in human polymorphonuclear leukocytes and monocytes. PMID- 6247400 TI - Effect of C. parvum on intratumor immunity to the T1699 mammary adenocarcinoma. PMID- 6247399 TI - Elicitation of anti-viral cytotoxic T lymphocytes with purified viral and H-2 antigens. AB - The minimal molecular requirements for elicitation of secondary anti-Sendai virus CTL were investigated. The hemagglutinin-neuraminidase (HN) glycoprotein of Sendai virus and the H-2Kk glycoprotein of YAC tumor cells were purified and incorporated into phospholipid vesicles. These unilamellar liposomes were then tested for the ability to elicit H-2 restricted secondary anti-Sendai virus CTL. The results indicate that these well-defined vesicles were capable of eliciting secondary anti-Sendai virus CTL which lysed only target cells possessing the H 2Kk haplotype and modified with inactivated Sendai virus. PMID- 6247401 TI - Stimulation of protein phosphorylation by epidermal growth factor in pig skin (epidermis). AB - Incorporation of 32P-orthophosphoric acid into pig epidermal proteins was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The incorporation was observed in 2 major and 2 minor peaks with approximate molecular weights of 52,000 and 27,000, 17,000, and 12,000 respectively. Treatment with epidermal growth factor (EGF) consistently increased 32P incorporation into all 4 peaks. The stimulation was both time- and dose dependent, and was not inhibited by the simultaneous addition of cycloheximide. In our previous study (submitted to J Invest Dermatol), we observed that EGF increased the cyclic GMP level in the same pig skin (epidermal) system. The possibility that the increased cyclic GMP leads to the protein phosphorylation observed in the present study was considered but ruled out because (1) the addition of cyclic GMP does not mimic the EGF treatment, (2) simultaneous addition of EGF and cyclic GMP stimulate phosphorylation to the same degree as the addition of EGF alone and (3) EGF stimulates phosphorylation in 20 min whereas the EGF induced increase in the cyclic GMP level takes 60 min. PMID- 6247402 TI - [Effectiveness of cefotaxime and other antibiotics to the typhoid and paratyphoid B carriers with gall stones and typhoid fever (author's transl)]. PMID- 6247403 TI - [Effect of dibutyryl cyclic AMP on hemodynamics and metabolism of carbohydrates and lipid after extracorporeal circulation in cardiac surgical patients (author's transl)]. PMID- 6247404 TI - [Structure, metabolism and function of poly (ADP-ribose) (author's transl)]. PMID- 6247405 TI - Puzzling liver nodules: important diagnostic aspects of focal nodular hyperplasia and liver cell adenoma. PMID- 6247406 TI - Ultraviolet light--denatured DNA/anti-ultraviolet light--denatured DNA immune complex nephritis in rabbits. AB - Two groups of preimmunized rabbits were studied during a 3-month course of daily intravenous injections of uv DNA in amounts sufficient to neutralize circulating antibody. One group was given high-molecular-weight uv DNA, and the other group, US uv DNA. Rabbits receiving US uv DNA formed potentially more damaging immune complexes, since this group of animals developed greater rises in blood urea and greater falls in C3. Circulating immune complexes were demonstrated in both groups of animals with the macromolecular IgG assay. Both groups of animals developed evidence of immune complex-mediated glomerular nephritis as evidenced by heavy granular deposits of IgG and C3 in the glomeruli. The results suggest that immune complexes formed with US uv DNA may be more nephrotoxic. This study provides further direct evidence that DNA/anti-DNA immune complexes are capable of glomerular localization with resulting tissue damage. PMID- 6247407 TI - Oxygen-detoxifying enzymes in neutrophils of infants and their mothers. AB - The oxygen-detoxifying enzymes of neutrophils, SOD, GPX, and catalase, were measured in neutrophils obtained from normal human infants, their mothers, and controls to determine whether or not the impaired functions of infant neutrophils might be related to a decreased ability of these cells to detoxify reactive forms of oxygen. The rationale was based on the following. (1) Defective functions have been reported in neutrophils sustaining oxidative damage. (2) Increased oxidative metabolism and decreased functions can be demonstrated concomitantly in infant neutrophils. (3) Neutrophils from infants may be analogous to infant erythrocytes, cells known to exhibit increased susceptibility to oxidative injury and dysfunctions that are apparently related to deficiencies of GPX and catalase. SOD activity was similar in neutrophils obtained from infants, their mothers, and controls, whereas both GPX and catalase were significantly decreased in infant cells. The data suggest that infant neutrophils were rendered susceptible to oxidative damage and possibly to defective function by an imbalance of oxygen detoxifying enzymes. PMID- 6247408 TI - Regulation of vertebrate liver HMG-CoA reductase via reversible modulation of its catalytic activity. AB - We have investigated the comparative biochemistry of in vitro regulation of HMG CoA reductase (EC 1.1.1.34) in microsomal preparations from the livers of nine vertebrates. In all instances, reductase activity was rapidly and profoundly decreased by addition of MgATP. Reductase activities were restored to near or above initial levels after removal of MgATP and incubation with a crude, low molecular weight phosphatase preparation from rat liver cytosol. Restoration of reductase activity was inhibited both by NaF and by pyrophosphate, known inhibitors of phosphoprotein phosphatase activity. Liver cytosol of species other than the rat exhibits reductase phosphatase activity. The converter enzymes that catalyze modulation of MG-CoA reductase activity (reductase kinase and reductase phosphatase) thus appear to be ubiquitous in vertebrate liver. Interconversion in vitro of active and inactive forms of reductase probably is general for vertebrate liver also. The majority of the reductase present in vertebrate liver may be present in a catalytically inactive or latent form in vivo. Under the experimental conditions used, the fraction present in the active form is, for a given species, quite constant. Species to species, from 20-45% of the reductase appears to be present in the active form. PMID- 6247409 TI - Influence of adipocyte isolation by collagenase on phosphodiesterase activity and lipolysis in man. AB - The maximum phosphodiesterase activity (Vmax) with low and high Km was, respectively, 10- and 3-times greater in tissue fragments than in collagenase isolated adipocytes obtained from subcutaneous fat layers in man. The exposure of such tissue fragments to collagenase of various origins in order to isolate the fat cells resulted in a 60-70% inhibition of phosphodiesterase (PDE) activity. Noradrenaline- and isopropyl noradrenaline-induced rates of lipolysis were more rapid in the isolated fat cells than in the tissue fragments. The sensitivity to catecholamines, however, was the same for the two tissue preparations. Nor did they differ in respect to the effect of theophylline, a PDE inhibitor, on the rate of lipolysis. The time curve for cyclic AMP accumulation was significantly higher in the isolated adipocytes than in tissue fragments in the presence of isopropyl noradrenaline. It is concluded that the greater lipolytic response of collagenase-isolated adipocytes than of tissue fragments to catecholamines may be attributed, at least in some measure, to the higher concentration of cyclic AMP resulting from a decrease in PDE activity. PMID- 6247410 TI - Synthesis of molecular species of glycerophospholipids from diglyceride-labeled brain microsomes. AB - Selectivity of CDP-choline:diacylglycerol choline phosphotransferase and CDP ethanolamine:diacylglycerol ethanolamine phosphotransferase for molecular species of diglyceride has been studied in rat brain microsomes in vitro. Diglyceride labeled microsomes were prepared by incubation with labeled sn-glycerol-3 phosphate; the microsomes were then incubated with CDP-choline or CDP ethanolamine for different time intervals. Experimental data extrapolated to zero time incubation were taken into account for evaluating species specificity. A small selectivity for diglyceride species has been demonstrated for the choline phosphotransferase, but the ethanolamine phosphotransferase was found to convert hexaenoic diglyceride into phospholipid at the highest rate. PMID- 6247411 TI - Reconstruction of the floor of the mouth by a free dorsalis pedis flap with microvascular anastomosis. AB - A new one stage technique for reconstruction of the floor of the mouth is described, using the free dorsalis pedis artery flap. Five cases are presented in this series, the indications, implications, possibilities and technique of this free flap in the intra-oral region are discussed. PMID- 6247412 TI - Cell-surface antigens associated with dualtropic and thymotropic murine leukemia viruses inducing thymic and nonthymic lymphomas. AB - Unique type-specific antigens were detected on cells infected with dualtropic and thymotropic viruses isolated and x-ray-induced T cell- and B cell-malignant lymphomas of C57BL/6 mice. These antigens were defined by membrane fluorescence with antisera made in rabbits against rabbit cells chronically infected with cloned virus. The antisera were qualitatively absorbed with a group of cells chronically infected with related dualtropic, ecotropic, and xenotropic viruses. The absorbed antisera detected type-specific, virus-related cell-surface antigens that were unique for different dualtropic virus isolates. The unabsorbed sera also reacted with antigens found specifically on ecotropic and xenotropic virus infected cells. These findings support the contention that T cell lymphoma (TCL) inducing and B cell lymphoma (BCL)-inducing viruses isolated from x-irradiated C57BL/6 mice are env gene recombinants in which ecotropic gene sequences have been substituted by xenotropic sequences. We found that unique antigenicities are associated with each TCL-inducing and BCL-inducing dualtropic virus, and that the thymotropic TCL-inducing virus isolates (e.g., 136.5 adn 136.7 viruses) represent a separate serologic group, different from the dualtropic TCL-inducing viruses. By using a series of absorbed antisera in microimmunofluorescence tests we could perform serologic virus mapping of dualtropic clones isolated by us or by others and relate them serologically to previously isolated clones. These virus mapping experiments indicated that many serologically different recombinant viruses can be isolated from C57BL/6 mice. It is suggested that many distinct recombinant viruses may exist in lymphomagenic C57BL/6 mice, some of which are associated with specific lymphoma induction. PMID- 6247413 TI - Failure of rabbit neutrophils to secrete endogenous pyrogen when stimulated with staphylococci. AB - Cells obtained from acute peritoneal exudates in rabbits were separated into neutrophil and mononuclear populations by centrifugation on colloidal silica gradients. When these populations were separately incubated in tissue culture medium in the presence of opsonized Staphylococcus epidermidis, endogenous pyrogen was secreted only by the adherent cells of the mononuclear population. Pyrogen production by neutrophils could not have amounted to as much as 1% of the pyrogen produced by macrophages. When mononuclear cells were added back to purified neutrophils, no pyrogen was produced that could not be accounted for by the number of macrophages added. Rabbit blood cells were similarly fractionated on colloidal silica gradients. Again, endogenous pyrogen was made only by the adherent mononuclear population. The neutrophils isolated on these gradients appeared to be morphologically normal and were 85% viable as judged by dye exclusion. They showed normal random motility. Both blood and exudate neutrophils responded chemotactically to N-formyl Met-Leu-Phe, and blood neutrophils responded chemotactically to zymosan-activated serum. Both kinds of neutrophils phagocytosed zymosan particles and both killed opsonized S. epidermidis in a roller tube system. Both blood and exudate neutrophils showed normal superoxide production when stimulated with opsonized zymosan particles. This evidence suggests that macrophages are the only source of endogenous pyrogens, and that pyrogens secreted by cell populations that are rich in neutrophils are to be attributed to the monocytes or macrophages that they contain. PMID- 6247414 TI - Erythroleukemia induction by replication-competent type C viruses cloned from the anemia- and polycythemia-inducing isolates of Friend leukemia virus. AB - In this study, the biological properties of the replication-competent viruses, F MuLVA, present in the anemia-inducing isolate of Friend leukemia virus complex (FV-A); and F-MuLVP, present in the polycythemia-inducing isolate of Friend leukemia virus complex (FV-P) have been examined. BALB/c mice infected as newborns with clonal isolates of F-MuLVA or F-MuLVP become anemic and show splenic enlargement characterized by an increased proportion of cells that resemble immature nucleated erythroid cells. In addition, the spleens of these F MuLVA- or F-MuLVP-infected mice contain a markedly increased proportion of both erythropoietin-dependent erythroid progenitor cells and spectrin-containing erythroid cells. These results suggest that Friend murine leukemia virus (F-MuLV) by itself can induce an erythroleukemic transformation in newborn BALB/c mice similar to that induced by the anemia-inducing spleen focus-forming virus (SFFVA) in newborn or adult mice. Kinetic studies indicated that the alterations in hemopoietic cell populations induced by F-MuLVA or F-MuLVP in newborn BALB/c mice occurred more slowly than the rapid changes observed after infection with FV-A. In addition, adult BALB/c mice were fully susceptible to the erythroleukemic transformation induced by either SFFVA or SFFVP, whereas only newborn mice were susceptible to F-MuLV. Taken together, these results suggest that, although the replication-defective Friend spleen focus-forming viruses appear to be the major determinant of erythroleukemia induction in adults, the replication-competent helper F-MuLV also have erythroleukemic potential when assayed in newborn animals. PMID- 6247415 TI - Ultrastructural characterization in acidophil adenoma with 2 types of secreting cells. PMID- 6247416 TI - Acupuncture enhanced dorsal root antidromic activity. PMID- 6247417 TI - Fusion of phospholipid vesicles with planar phospholipid bilayer membranes. I. Discharge of vesicular contents across the planar membrane. AB - Multilamellar phospholipid vesicles are introduced into the cis compartment on one side of a planar phospholipid bilayer membrane. The vesicles contain a water soluble fluorescent dye trapped in the aqueous phases between the lamellae. If a vesicle containing n lamellae fuses with a planar membrane, an n-1 lamellar vesicle should be discharged into the opposite trans compartment, where it would appear as a discernible fluorescent particle. Thus, fusion events can be assayed by counting the number of fluorescent particles appearing in the trans compartment. In the absence of divalent cation, fusion does not occur, even after vesicles have been in the cis compartment for 40 min. When CaCl2 is introduced into the cis compartment to a concentration of greater than or equal to 20 mM, fusion occurs within the next 20 min; it generally ceases thereafter because of vesicle aggregation in the cis compartment. With approximately 3 x 10(8) vesicles/cm3 in the cis compartment, about 25-50 fusion events occur following CaCl2 addition. The discharge of vesicular contents across the planar membrane is the most convincing evidence of vesicle-membrane fusion and serves as a model for that ubiquitous biological phenomenon--exocytosis. PMID- 6247418 TI - Fusion of phospholipid vesicles with planar phospholipid bilayer membranes. II. Incorporation of a vesicular membrane marker into the planar membrane. AB - Fusion of multilamellar phospholipid vesicles with planar phospholipid bilayer membranes was monitored by the rate of appearance in the planar membrane of an intrinsic membrane protein present in the vesicle membranes. An essential requirement for fusion is an osmotic gradient across the planar membrane, with the cis side (the side containing the vesicles) hyperosmotic to the opposite (trans) side; for substantial fusion rates, divalent cation must also be present on the cis side. Thus, the low fusion rates obtained with 100 mM excess glucose in the cis compartment are enhanced orders of magnitude by the addition of 5-10 mM CaCl2 to the cis compartment. Conversely, the rapid fusion rates induced by 40 mM CaCl2 in the cis compartment are completely suppressed when the osmotic gradient (created by the 40 mM CaCl2) is abolished by addition of an equivalent amount of either CaCl2, NaCl, urea, or glucose to the trans compartment. We propose that fusion occurs by the osmotic swelling of vesicles in contact with the planar membrane, with subsequent rupture of the vesicular and planar membranes in the region of contact. Divalent cations catalyze this process by increasing the frequency and duration of vesicle-planar membrane contact. We argue that essentially this same osmotic mechanism drives biological fusion processes, such as exocytosis. Our fusion procedure provides a general method for incorporating and reconstituting transport proteins into planar phospholipid bilayer membranes. PMID- 6247419 TI - Calcium sensitivity of the contractile system and phosphorylation of troponin in hyperpermeable cardiac cells. AB - Bundles of cells from rat right ventricular myocardium were made "hyperpermeable" by an overnight soak in 10 mM EGTA (McClellan and Winegrad. 1978. J. Gen. Physiol. 72:737-764). In this preparation the cytoplasmic concentration of Ca++ and ATP could be controlled while sarcolemmal receptors and enzymes were retained. The Ca sensitivity of the tissues (as indicated by the pCa for 50% maximum activation) was altered to different extents in the presence of [32Pgamma]ATP by treatment with cyclic nucleotides, catecholamines, or a low concentration of nonionic detergent. The proteins of the tissue were then isolated by SDS-polyacrylamide gel electrophoresis, and the identity of 32P labeled proteins was determined. The Ca sensitivity is inversely related to the relative amount of 32P incorporated into the inhibitory subunit of troponin (TNI). Extrapolation of the relation to the lowest Ca sensitivity observed gives a stoichiometry of about 0.8 mol PO4 per mol TNI. These results support the hypothesis that Ca sensitivity of cardiac myofibrils is regulated by a phosphrylation of TNI that is stimulated by cyclic AMP (cAMP) and inhibited by cGMP. PMID- 6247420 TI - Cyclic nucleotide regulation of the contractile proteins in mammalian cardiac muscle. AB - The contractile system of rat cardiac muscle that has been made hyperpermeable by soaking the tissue in EGTA (McClellan and Winegrad. 1978. J. Gen. Physiol. 72:737 764) can be probed directly with Ca buffer from the bathing solution without significant interference from either sarcoplasmic reticulum or mitochondria on the Ca concentration. Changes in Ca-activated force are due therefore to changes in the properties of the contractile system itself and not to regulation of Ca concentration. The addition of cAMP, cGMP, and GTP, guanylyl imidodiphosphate (GMP-PNP), or epinephrine to the bath does not alter maximum Ca-activated force, but when these drugs are added with 1% nonionic detergent to the bath, contractility increases by as much as 180%. An inhibitor of phosphodiesterase must be present for the inotropic effect of cAMP but not cGMP, GTP, GMP-PNP, or epinephrine. The inotropic response to cAMP is independent of the Ca sensitivity of the contractile system, but guanine nucleotides enhance contractility only when Ca sensitivity is not high. The inotropic effect of epinephrine is inhibited to a large extent by cGMP but not by GMP-PNP. These data can be explained by a model in which contractility is enhanced by a cAMP-regulated phosphorylation that can be controlled through the beta-receptor adenylate cyclase complex in the sarcolemma. The regulation involves two reactions, one a phosphorylation and a second that occurs in the presence of detergent. Phosphorylation of neither the myosin light chain nor the inhibitory subunit of troponin appears to be involved in this mechanism for regulating contractility. PMID- 6247421 TI - Calcium effects on frog retinal cyclic guanosine 3', 5'-monophosphate levels and their light-initiated rate of decay. AB - When retinal sections were isolated from dark-adapted bullfrogs and placed in normal ringer's solution, they contained 40.7 +/- 0.2 pmol cGMP/mg protein (mean +/- SEM, 30 samples). When isolated, dark-adapted retinal sections were removed from normal ringer's solution and placed in calcium-deficient ringer's solution with 3 mM EGTA, there was about a threefold rise in cyclic GMP (cGMP) levels by 1.5 min and about a 10-fold rise by 5 min. The cGMP level remained high with no detectable decrease for at least 40 min (the longest time measured). When isolated, dark- adapted retinal sections were removed from normal ringer's solution and placed in ringer's solution which contained high- calcium (20 mM CaCl(2)), there was a slow but significant decrease in cGMP levels. After 20 min in high-calcium ringer's solution the cGMP level was 0.58 +/- 0.07 (mean +/- SEM, eight samples) of the cGMP level in normal ringer's solution incubated for the same time. The rate at which 10-fold elevated cGMP levels in low calcium decreased upon illumination was examined using quick-freezing techniques on the retinal sections. The elevated cGMP level in retinal sections incubated in low calcium decreased upon illumination was examined using quick-freezing techniques on the retinal sections. The elevated cGMP level in retinal sections incubated in low-calcium ringer's solution was found to decay about 15-fold faster than cGMP levels in retinal sections incubated in normal ringer's solution. The CGMP level in low calcium was significantly different (P=0.005) after 1 s illumination, whereas the cGMP level in normal calcium was not significantly different. PMID- 6247422 TI - The permeability of the endplate channel to organic cations in frog muscle. AB - The relative permeability of endplate channels to many organic cations was determined by reversal-potential criteria. Endplate currents induced by iontophoretic "puffs" of acetylcholine were studied by a Vaseline gap, voltage clamp method in cut muscle fibers. Reversal potential changes were measured as the NaCl of the bathing medium was replaced by salts of organic cations, and permeability ratios relative to Na+ ions were calculated from the Goldman-Hodgkin Katz equation. 40 small monovalent organic cations had permeability ratios larger than 0.1. The most permeant including NH4+, hydroxylamine, hydrazine, methylamine, guanidine, and several relatives of guanidine had permeability ratios in the range 1.3--2.0. However, even cations such as imidazole, choline, tris(hydroxymethyl)aminomethane, triethylamine, and glycine methylester were appreciably permeant with permeability ratios of 0.13--0.95. Four compounds with two charged nitrogen groups were also permeant. Molecular models of the permeant ions suggest that the smallest cross-section of the open pore must be at least as large as a square, 6.5 A x 6.5 A. Specific chemical factors seem to be less important than access or friction in determining the ionic selectivity of the endplate channel. PMID- 6247423 TI - The permeability of endplate channels to monovalent and divalent metal cations. AB - The relative permeability of endplate channels to monovalent and divalent metal ions was determined from reversal potentials. Thallium is the most permeant ion with a permeability ratio relative to Na+ of 2.5. The selectivity among alkali metals is weak with a sequence, Cs+ greater than Rb+ greater than K+ greater than Na+ greater than Li+, and permeability ratios of 1.4, 1.3, 1.1, 1.0, and 0.9. The selectivity among divalent ions is also weak, with a sequence for alkaline earths of Mg++ greater than Ca++ greater than Ba++ greater than Sr++. The transition metal ions Mn++, Co++, Ni++, Zn++, and Cd++ are also permeant. Permeability ratios for divalent ions decreased as the concentration of divalent ion was increased in a manner consistent with the negative surface potential theory of Lewis (1979 J. Physiol. (Lond.). 286: 417--445). With 20 mM XCl2 and 85.5 mM glucosamine.HCl in the external solution, the apparent permeability ratios for the alkaline earth cations (X++) are in the range 0.18--0.25. Alkali metal ions see the endplate channel as a water-filled, neutral pore without high-field strength sites inside. Their permeability sequence is the same as their aqueous mobility sequence. Divalent ions, however, have a permeability sequence almost opposite from their mobility sequence and must experience some interaction with groups in the channel. In addition, the concentrations of monovalent and divalent ions are increased near the channel mouth by a weak negative surface potential. PMID- 6247424 TI - Effects of ammonium ions on endplate channels. AB - Miniature endplate currents, recorded from voltage-clamped toad sartorius muscle fibers in solutions containing ammonium ions substituted for sodium ions, were increased in amplitude and decayed exponentially with a slower time constant than in control (Na) solution. The peak conductance of miniature endplate currents was also greater in ammonium solutions. The acetylcholine null potential was -2.8 +/- 0.8 mV in control solution, and shifted to 0.9 +/- 1.6 mV in solutions in which NH4Cl replaced half the NaCl. In solutions containing NH4Cl substituted for all the NaCl, the null potential was 6.5 +/- 1.3 mV. Single channel conductance and average channel lifetime were both increased in solutions containing ammonium ions. The exponential relationship between the time constant of decay of miniature endplate currents or channel lifetime and membrane potential was unchanged in ammonium solutions. A slight but consistent increase in peak conductance during miniature endplate currents and single channel conductance was seen as membrane potential became more positive (depolarized) in both control and ammonium solutions. Net charge transfer was greater in ammonium solutions than in control solution, whether measured during a miniature endplate current or through a single channel. The results presented here are consistent with an endplate channel model containing high field strength, neutral sites. PMID- 6247425 TI - Induction of endogenous murine type C virus by ultraviolet-irradiated herpes simplex virus: effect of metabolic inhibitors. AB - Ultraviolet-irradiated herpes simplex virus (u.v.-HSV) induced endogenous xenotropic type C virus from AI--2 cells, derived from the BALB/c mouse, as determined by infectious centre focus-forming assay on permissive normal rat kidney (NRK) cells. The number of cells induced to release type C virus by irradiated HSV was dependent on the level of u.v. exposure received by the HSV. Optimal induction occurred when cells were infected with irradiated HSV during their exponential growth phase. Virus induction decreased under conditions of simultaneous cellular exposure to hydroxyurea or actinomycin D, inhibitors of DNA and RNA synthesis, respectively, with actinomycin D having a greater inhibitory effect. This suggests that both DNA and RNA synthesis are required for irradiated HSV induction of murine xenotropic virus. Hydroxyurea decreased induction in the first few hours after infection of A1--2 cells with irradiated HSV, suggesting that the biological events involving DNA synthesis which are required for induction by u.v.-HSV occur shortly after infection. PMID- 6247426 TI - Macrophage extrinsic antiviral activity during herpes simplex virus infection. AB - Peritoneal macrophages from mice infected with herpes simplex virus type 2 (HSV 2) exhibited extrinsic antiviral resistance. When the macrophages were co cultivated in vitro with virus-infected cells the yield of virus was reduced markedly. Activity was not present 1 to 2 days p.i., peaked at 3 to 4 days, declined by 7 days and was absent at 14 days after HSV-2 infection. The extrinsic antiviral activity was limited to the adherent peritoneal macrophage population. The macrophage antiviral activity was also dose-dependent, with approx. 10(6) macrophages (macrophage: host cell ratio of approx. 2:1) reducing virus plaques by greater than 90% and virus yield 1.5 to 3.0 log10. Comparable extrinsic antiviral activity was also exhibited by Corynebacterium parvum- or thioglycollate-elicited peritoneal macrophages. The macrophage activity was not species-specific, activity on Vero cells or syngeneic mouse embryo fibroblasts being comparable. Activity was also not virus-specific, as the active macrophages also inhibited vesicular stomatitis virus (VSV). The antiviral effects required viable macrophages; cell lysates did not inhibit virus growth. PMID- 6247427 TI - The polypeptides of infectious bronchitis virus (IBV-41 strain). AB - The Massachusetts strain of avian infectious bronchitis virus was purified from embryonated hens' eggs. Four major species of apparent mol. wt. 90 000, 52 000, 29 000 and 26 000 were resolved by SDS-polyacrylamide gel electrophoresis. Omission of reducing agent failed to resolve the 29 000 mol. wt. component. Labelling of acrylamide gels with 125I-concanavalin A indicated that polypeptides of mol. wt. 90 000, 29 000 and 26 000 were glycosylated and, in the absence of reducing agent, that the 29 000 species migrated as a dimer in the 5000 mol. wt. region. Purified IBV radio-iodinated with Bolton and Hunter reagent, which banded as a single peak of radioactivity in Metrizamide gradients, was found to contain bands of radioactivity when analysed by SDS-PAGE, corresponding to the polypeptides of mol. wt. 90 000, 52 000 and 29 000 resolved in stained gels. Disruption of IBV particles in Triton X-100 released two subviral particles, a 16 nm spike which comprised polypeptides of 90 000, 52 000 and 29 000 mol. wt. and another denser spherical particle of 25 to 45 nm which contained RNA and the 52 000 and 26 000 polypeptides. PMID- 6247428 TI - Virus-specific basic phosphoproteins associated with herpes simplex virus type a (HSV-1) particles and the chromatin of HSV-1-infected cells. AB - Herpes simplex type 1 Angelotti (HSV-1 ANG) virions were shown to contain two major acid-soluble proteins, BP1 and 2, which by size and charge analysis were also found to be associated with chromatin isolated from HSV-1 ANG-infected African green monkey kidney cells (HSV-chromatin). BP1 and 2 proved to exist in a phosphorylated state both in virions and in HSV-chromatin. BP1 consisted of a single polypeptide of 38 K mol. wt. which was correlated to the tegument protein VP22. In SDS-polyacrylamide gels BP2 migrated as a single polypeptide band with an apparent mol. wt. of 12 K. Urea gel analysis revealed that BP2 consisted of three components, BP2a, b and c, of different phosphate contents. Arguments were provided that these components probably represent different polypeptides of similar mol. wt. HSV-chromatin, in addition to BP1, BP2a, b and c contained a further major virus-induced basic phosphopolypeptide of mol. wt. 65 K which was not detected in acid-extracts of mature virions. PMID- 6247429 TI - Electron microscopic immunoperoxidase studies on the accumulation of virus antigen in cells infected with Shope fibroma virus. AB - The indirect immunoperoxidase technique was used to investigate the development of the virus-specific intracellular and cell membrane antigens in cells infected with the Shope fibroma virus. Starting with 6 h p.i., virus antigen formed distinct inclusions within the cytoplasm frequently enclosed by endoplasmic reticulum. The endoplasmic reticulum disappeared almost completely 10 to 12 h p.i., coincidentally with the beginning of virus formation. The virus antigen was distributed throughout the cytoplasm. At the same time virus-induced antigen began to appear at the cell membrane and subsequently increased. No cytochemical staining could be observed on the endoplasmic reticulum, within the nucleus and within immature and mature virus particles. The correlation between antigen synthesis and changes in cell ultrastructure is discussed. PMID- 6247430 TI - Intertypic recombinants of herpes simplex viruses. PMID- 6247431 TI - Isolation of a virus closely related to gibbon ape leukaemia virus from cells infected with virus (HL-23V) released by human leukaemic cells. AB - Canine thymus cells infected with virus (HL-23V) produced by human acute myelogenous leukaemia cells in culture were shown in previous reports to produce transforming and non-transforming type C virus similar or identical to the simian sarcoma virus complex SSV(SSAV) and to induce tumours in marmoset monkeys (Bergholz et al. 1977a). In these earlier studies the appearance of breakthrough foci at low dilutions of antiserum in neutralization tests with high-titred anti SSV(SSAV) serum suggested the presence of another virus, distinct from SSV (SSAV). We now report the isolation of this component and, by comparative neutralization analysis, demonstrate that it is most closely related to gibbon ape leukaemia virus (GALV). It is distinguished from SSV(SSAV) by kinetics of neutralization and molecular hybridization experiments. This component was readily cloned both from virus produced by HL-23V chronically-infected canine thymus cells established by Teich et al. (1975) when HL-23V was first isolated and from virus produced by HL-23V-induced marmoset tumour cells in culture. The presence of this component in the original leukaemic cell cultures is discussed. PMID- 6247432 TI - Integration and transcription of virus DNA in herpes simplex virus transformed cell lines. AB - The physical state of the HSV I DNA present in two biochemically transformed cell lines, a revertant line and a supertransformed cell line, was determined. These cells all contained fragments of the HSV genome and the transformed and supertransformed cell lines expressed virus thymidine kinase. It was found that the virus DNA in these cells was maintained in a complex state with approximately half of the HSV DNA present in a covalently integrated state and the other half in a non-integrated state. There was no major cell line difference in the distribution of integrated and non-integrated virus DNA. RNA transcripts representing 5% of the HSV I genome are present in each of these lines. This is more than is required to code for the virus thymidine kinase present in the transformed and supertransformed cell lines and suggests the presence of other virus proteins in these cells. PMID- 6247433 TI - Deletions of the terminal sequences in the genomes of the white pock (u) and host restricted (p) mutants of rabbitpox virus. AB - The DNAs of wild-type rabbitpox virus (u+.p+), and selected u (white pock, u.p+) and p (white pock, PK-15 cell non-permissive, u.p) mutants were compared by restriction enzyme analysis. The cleavage fragments produced by digestion with HindIII or EcoRI endonucleases were separated by agarose gel electrophoresis. Deletions of approx. 10 x 10(6) were recognized at the right-hand terminus of each u mutant (three isolates), whereas deletions of 5 x 10(6) to 20 x 10(6) were detected at the left-hand terminus of each p mutant (nine isolates), Rapidly renaturing terminal restriction fragments, indicative of the covalent cross links, were only found at the terminus unaffected by deleted sequences. Recombinant viruses that were wild-type in both genetic characters and in restriction pattern were recovered from mixed infections involving u and p mutants, but no genetic interaction was detected between crosses involving only u or p mutants. The p mutants were divided into two non-permissive classes dependent on their biochemical expression in PK-15 cells: the 'early' class which failed to replicate virus DNA and synthesized only the 'early' polypeptides and the 'late' class which appeared to be normal both in virus DNA and polypeptide synthesis. There was no correlation between the extent of the left-hand terminal deletion and the extent of permissiveness of the p mutants in PK-15 cells. PMID- 6247434 TI - Polyamine metabolism in MRC-5 cells infected with human cytomegalovirus. AB - The rate of putrescine uptake into MRC-5 cells increased markedly following infection with human cytomegalovirus (HCMV). Enhanced incorporation occurred immediately after infection and the highest levels were attained following the production of infectious, progeny virus. Parallel kinetic changes in the utilization of radio-labelled putrescine were shown by the amounts of spermidine and spermine recovered from infected cells as radioactive derivatives. A temporal correlation was found between these changes in polyamine metabolism and the synthesis of virus DNA. Methylglyoxalbis(guanylhydrazone), an inhibitor of spermidine and spermine synthesis, did not affect virus replication if HCMV infected cells were exposed to the inhibitor after completion of the eclipse phase of the virus growth cycle. These results show that polyamine metabolism is required only during the initial stages of HCMV replication. PMID- 6247435 TI - The polypeptide composition of isolated surface projections of avian infectious bronchitis virus. AB - Disruption of avian infectious bronchitis virus (IBV) particles with 4% Triton X 100 and 1.0 M-KCl and centrifugation through a sucrose gradient containing 0.1% Triton X-100 and 1.0 M-KCl enabled separation of the petal-shaped surface projections. By negative-contrast electron microscopy the separated projections appeared mainly as rosettes containing 3 to 12 projections radiating from a central core, although single projections and rosettes containing up to 16 projections were seen. SDS-PAGE of these preparations revealed two polypeptides of 86,000 and 66,000 mol. wt. The larger polypeptide was glycosylated. PMID- 6247436 TI - Recombination in adenovirus. I. Analysis of recombinant viruses under non selective conditions. AB - A method is described, based on an approach previously employed for the mapping of adenovirus ts mutants (Grodzicker et al. 1975), for the identification of recombinant viruses in the progeny of mixed infections of human HeLa cells with wild-type adenovirus types 2 and 5 under non-selective conditions. Differences in restriction enzyme sites for the endonuclease HpaI could be used to detect new recombinant DNA fragments in a yield of 3 to 6% after single mixed infections and yields up to 25% following three successive mixed infections. The recombinant nature of the new fragments was proved by the clonal isolation of recombinant viruses in similar yields. Analysis of one cloned recombinant pointed to the occurrence of multiple crossover events at different sites along the virus chromosome. The results are discussed in terms of a biochemical approach towards the study of the mechanism of general genetic recombination in human cells as well as with respect to the evolution of adenoviruses. PMID- 6247437 TI - Indirect enzyme-linked immunosorbent assay (ELISA) for the detection of Coxsackievirus group B antibodies. AB - An indirect, solid phase, microplate enzyme-linked immunosorbent assay (ELISA) was found to be highly sensitive and reliable for detecting antibodies to the group B Coxsackieviruses and other picornaviruses. Conditions for obtaining maximum sensitivity and reproducibility of the indirect ELISA are described. Antibody titres were comparable to those obtained by the virus neutralization test and over 50 times higher than those obtained by the complement-fixation test. Purified virions used in the indirect ELISA reacted with low levels of cross-reacting heterotypic antibodies elicited by each of the six group B Coxsackieviruses, although homotypic reactions resulted in highest titres. PMID- 6247438 TI - A sensitive method for quantification of vesicular stomatitis virus defective interfering particles: focus forming assay. AB - A focus-forming assay for the quantification of defective interfering (DI) particles of vesicular stomatitis virus (VSV) is described. This assay is based on the procedures described for lymphocytic choriomeningitis (LCM) virus by Popescu et al. (1976). Under appropriate conditions this focus-forming assay can quantify fewer than 100 DI particles/ml in a preparation containing a large number of infectious particles. PMID- 6247439 TI - Isolation of a recombinant between simian and bovine rotaviruses. AB - A recombinant between simian rotavirus, simian agent 11 (SA-11) and bovine rotavirus, neonatal calf diarrhoea virus (NCDV), was obtained by mixed infection of MA-104 cells with NCDV and u.v.-irradiated SA-11 virus, and isolation of a plaque formed in the presence of anti-NCDV serum. The genome of the recombinant contained dsRNA segments 4, 5 and 10 derived from SA-11 virus and segments 1, 2, 3, 6 and 11 derived from NCDV, and segments 7, 8 and 9 of undetermined origin. Polypeptides VP4, VP5, VP7a, VP7b, NCVP1 and MCVP3 were derived from SA-11 virus and polypeptides VP1, VP2, VP3, VP6, VP8, NCVP2a and NCVP2b from NCDV. Haemagglutination of the recombinant was inhibited and its infectivity neutralized by the antiserum against SA-11 virus but not by anti-NCDV serum. PMID- 6247440 TI - Glycopeptide composition of hepatitis B surface antigen. AB - Three major polypeptides of hepatitis B surface antigen (HBsAg), with mol. wt. 22,000 (p22), 27,000 (p27) and 68,000 (p68), were separated by preparative SDS PAGE. These three peptides as well as intact HBsAg were found to have almost identical amino acid compositions and carbohydrate was detected in p27 and p68 by PAS staining. Papain treatment of p68 produced two distinct peptides p27 and p22. Moreover, when an artificial mixture of p27 and p22 in a ratio of 1:1 was treated with 0.2 M-periodate for 30 min at 37 degrees C, only p22 was detectable. These results suggest that p68 is composed of p27 and p22, and that p27 is a glycosylated product of p22. Thus, from the evidence obtained, it is possible that p22 (22,000 peptide) is the minimum size of the unique hepatitis B virus (HBV) gene product involved. PMID- 6247441 TI - Comparative neurovirulence and latency of HSV1 and HSV2 following footpad inoculation in mice. AB - The effect of virus dose and animal age on the appearance of acute and latent neurologic infection by HSV1 and HSV2 was studied in Balb/c and ICR mice inoculated in the footpad. At low viral doses HSV2 was found to be 1,500 times more neurovirulent than HSV1. At high doses there was no difference in neurovirulence. Age-acquired resistance to disease was shown to be less complete with HSV2 than with HSV1. Neurovirulence was shown to be associated with spread of infection to the spinal ganglia. The data indicate that the factor(s) responsible for the differential neurovirulence of these two viruses is related to events at the level of the footpad and/or sciatic nerve. PMID- 6247442 TI - Comparison of solid phase test systems for demonstrating antibodies against hepatitis A virus (anti-Hav) of the IgM-class. AB - Three methods were compared for determining anti-HAV of the IgM class. In the first method flat-bottomed microtiter plates coated consecutively with anti-HAV of the IgG class and HAAg were incubated with patient serum and, after washing, peroxidase conjugated anti-mu was added. After subsequent incubation with substrate the enzymatic reaction was stopped and the optical density was measured. In the second method the solid phase was coated first with antibodies to IgM and after incubation with patient serum and subsequent incubations with HAAg and 125I anti-HAV of the IgG class radioactivity was counted. These two methods were compared with reorienting sucrose gradient ultracentrifugation, an established method for demonstrating specific IgM antibodies. The persistence of IgM anti-HAV in 103 sera drawn at different times after onset of jaundice was evaluated. Sera drawn up to 30 days after onset of hepatitis A were IgM anti-HAV positive with both of the first two methods. Forty-one to 90 days after onset of illness IgM anti-HAV could be demonstrated with the first method in 47% of the patients, in 94% with the second method, and in 82% with gradient centrifugation. The second method was most sensitive and could be adjusted so that at a serum dilution of 1:10(4) anti-HAV IgM was detected only up to six months after infection. In contrast to the first method, nonspecific reactions caused by rheumatoid factor were not detected with the second method. During a one-year period about 15,000 sera of patients with clinical diagnoses of acute hepatitis were tested; the positive results correlated well with the clinical data, and there was no indication of nonspecific positive results. PMID- 6247443 TI - The role of the pineal gland in stress. AB - A short survey of the results of our previous research into the protective role of the pineal gland against stress is given. The neuroendocrine aspect of a chronic auditory stress and the neuroendocrine aspect of ulcer disease in man were studied. Auditory stress: hypertrophy and hyperplasia of pinealocytes, hyperplasia of the STH, FSH, LTH and TSH cells, hypertrophy of the nuclei and nucleoli of the neuroglandular cells of the supraoptic and paraventricular nuclei, pronounced hyperplasia of the cells of the reticular zone of the adrenal gland, involution of the seminal epithelium, hyperplasia of the Leydig cells. Ulcer disease: numerous glial plates, cavities and acervuli in the pineal gland, numerous granules and vacuoles in the FSH cells, large and eccentrical nuclei in the LH cells, hyperplasia of the cells of the reticular zone of the adrenal gland, presence of the seminal tubules marked by signs of involution, hyperplasia of the Leydig cells. The results obtained point to the secretion of androgens and the insufficiency of the antiandrogenic function of the pineal gland both in auditory stress and ulcer disease. The anticancerogenic effect of the pineal gland would be based on its antiandrogenic function. PMID- 6247444 TI - Active site-specific reconstituted copper(II) horse liver alcohol dehydrogenase: a biological model for type 1 Cu2+ and its changes upon ligand binding and conformational transitions. AB - Insertion of Cu2+ ions into horse liver alcohol dehydrogenase depleted of its catalytic Zn2+ ions creates an artificial blue copper center similar to that of plastocyanin and similar copper proteins. The esr spectrum of a frozen solution and the optical spectra at 296 and 77 K are reported, together with the corresponding data for binary and ternary complexes with NAD+ and pyrazole. The binary complex of the cupric enzyme with pyrazole establishes a novel type of copper proteins having the optical characteristics of Type 1 and the esr parameters of Type 2 Cu2+. Ternary complex formation with NAD+ converts the Cu2+ ion to a Type 1 center. By an intramolecular redox reaction the cuprous enzyme is formed from the cupric enzyme. Whereas the activity of the cupric alcohol dehydrogenase is difficult to assess (0.5%-1% that of the native enzyme), the cuprous enzyme is distinctly active (8% of the native enzyme). The implications of these findings are discussed in view of the coordination of the metal in native copper proteins. PMID- 6247445 TI - Energy metabolism in rat brain synaptosomes from nembutal-anesthetized and nonanesthetized animals. PMID- 6247446 TI - Subcellular localization of folate turnover and folate-dependent enzyme activity in mouse brain. PMID- 6247447 TI - pH-induced alterations in dopamine synthesis regulation in rat brain striatal synaptosomes. PMID- 6247448 TI - Cerebral metabolic state during the ethanol withdrawal reaction in the rat. PMID- 6247449 TI - Studies of pargyline-monoamine oxidase binding using a spin label probe analog. PMID- 6247450 TI - Protein synthesis in a cell-free system from rat brain sensitive to ACTH-like peptides. PMID- 6247451 TI - Purification and some characteristics of an ACTH-sensitive protein kinase and its substrate protein in rat brain membranes. PMID- 6247452 TI - K+-induced accumulation of guanosine 3',5'-monophosphate in sympathetic ganglia. PMID- 6247453 TI - A case of nemaline myopathy with ophthalmoplegia and mitochondrial abnormalities. AB - A case of nemaline myopathy with ophthalmoplegia is reported. The patient was a 35-year-old man born of consanguineous parents. He had a myopathic face, high arched palate, nasal voice, scoliosis, very thin trunk and marked muscle weakness involving face, neck, limbs and trunk. He also had ptotis of the left eyelid and mild bilateral ophthalmoplegia, also detected by electrooculogram. Biopsy of gastrocnemius muscle revealed nemaline rods. At the ultrastructural level, the rods appeared to have axial and cross striations, and in cross-sections at high magnification they seemed to have a crystal lattice structure. Intranuclear rods were also observed. In addition to the rods, abnormal mitochondria including a number of paracrystalline inclusions were seen. PMID- 6247454 TI - Erythrocyte ghost Na+,K+-adenosine triphosphatase in Duchenne muscular dystrophy. AB - Erythrocyte ghost membranes have been prepared by two different methods from patients with Duchenne muscular dystrophy (DMD), carriers of DMD, patients with other neuromuscular diseases, and normal individuals. The susceptibility of the membrane Na+,K+-adenosine triphosphatase (ATPase) to the cardiac glycoside, ouabain, has been investigated using various assay conditions. A stimulation of the enzyme has not been detected under any of the conditions employed. Using either a "high salt" (100 mM NaCl, 20 mM KCl) or a "low salt" (1 mM NaCl, 2 mM KCl) assay in the presence of EGTA a reduced susceptibility of the enzyme to ouabain was observed in preparations from patients with DMD compared with those from normal individuals. This behaviour was not manifest in preparations from NAD carriers or from patients with other neuromuscular diseases. The response of the erythrocyte membrane Na+,K+-ATPase activity to changes in temperature has also been investigated. The temperature response of the enzyme from DMD and DMD carrier preparations was indistinguishable from that of normal preparations. In all cases a break in the Arrhenius plot occurred at 21 degrees C. PMID- 6247455 TI - Peripheral neuropathy due to perhexilene maleate. AB - Observations are presented on 3 patients, including one autopsy report, with peripheral neuropathy due to perhexilene maleate (Pexid). Clinically and biochemically perhexilene neuropathy presents features unusual for a drug-induced neuropathy. Patients liable to develop neuropathy can be recognised from clinical criteria or by the use of routine electrophysiological determinations of nerve conduction velocities. At this stage the neuropathy is readily reversible if perhexilene therapy is discontinued. We have sought to examine the problems entailed in the future safety of perhexilene and allied drugs. PMID- 6247456 TI - Clinical and pathological features of an autosomal recessive neuropathy. AB - Two siblings are described, ages 49 and 45 years, having a distinct hereditary motor and sensory neuropathy (HMSN) with severe peroneal nerve involvement. The neuropathic symptoms began in childhood. Both patients have sensorineural deafness. The proband was found to have a cardiac conduction abnormality in the absence of known ischemic heart disease. Electrodiagnostic studies were consistent with a demyelinating peripheral neuropathy. The presence of parental consanguinity and absence of affected individuals in succeeding or preceding generations suggested that the sensorimotor neuropathy in this family is inherited in an autosomal recessive manner. The sural nerve of the proband had significant loss of myelinated fibers and demyelination but few regenerating myelinated fibers and no onion-bulbs. The pathological findings, while nonspecific, are not characteristic of the hypertrophic, neuronal or intermediate types of HMSN. PMID- 6247457 TI - Erythrocyte membrane abnormalities in human myotonic dystrophy. AB - Membrane-bound enzyme activities and cardiac glycoside binding were determined in red blood cell membrane preparations from patients with myotonic dystrophy and in age matched controls. Na+-K+-activated ATPase activity was significantly increased in myotonic patients. [3H]Ouabain binding to erythrocyte membranes was also significantly increased in myotonic dystrophy patients. The Mg2+-ATPase (ouabain-insensitive) was, however, unchanged. The K+-stimulated paranitrophenyl phosphatase (KPNPPase) activity was markedly enhanced in myotonic patients as compared to controls. The kinetic analysis showed a marked change in Vmax of Na+ K+ ATPase with respect to the activation by Na+, K+ and ATP. However, the Km values were the same in control as well as in myotonic groups. The increased erythrocyte membrane Na+-K+-ATPase activity, KPNPPase and [3H]ouabain binding in myotonic patients supports the hypothesis that generalized membrane abnormality may be involved in pathogenesis of the human myotonic dystrophy. PMID- 6247458 TI - Lateral horn cells in progressive autonomic failure. AB - Estimates of cell loss in the intermediolateral columns of the thoracic cord in cases of progressive autonomic failure were made by counting nerve cells in the lateral grey horns from 21 such cases, and comparing (a) with "normal" controls, (b) with 3 cases of uncomplicated Parkinson's disease and (c) with 3 cases of multiple system atrophy without overt autonomic failure. It was found that all cases of autonomic failure had suffered severe cell loss; on average three quarters of their lateral horn cells were lost. The cases of uncomplicated Parkinson's disease did not differ from the controls; but the cases of multiple system atrophy without autonomic disturbances had lost about half their lateral horn cells. These findings are tabulated, and discussed. PMID- 6247459 TI - Triggering of locust jump by multimodal inhibitory interneurons. AB - 1. The locust jump is triggered by a sudden inhibition of activity in hindleg flexor tibiae motoneurons following cocontraction of the hindleg flexor and extensor tibiae muscles. The main result of this investigation was the identification of two interneurons (one for each hindleg) that monosynaptically inhibit flexor tibiae motoneurons and whose properties are all consistent with them being the trigger interneurons for initiating a jump. 2. These interneurons receive strong excitatory input from many sensory modalities (visual, auditory, tactile, and proprioceptive). Because of their multimodal response characteristics, we designated them M-neurons. A particularly strong excitatory input to each M-neuron is from both descending contralateral movement detector (DCMD) interneurons. 3. The threshold for spike initiation in the M-neurons is high (approximately 14 mV). As a consequence, input from any one sensory modality alone rarely initiates action potentials. 4. Each M-neuron is depolarized by sensory input from leg proprioceptors. We propose that proprioceptive feedback during the cocontraction phase depolarizes the M-neurons to decrease their threshold, thus enabling extrinsic sensory stimuli to generate action potentials in both M-neurons and in so doing trigger a jump. The function of the proprioceptive gating of inhibitory transmission from the various sensory systems to the flexor motoneurons (via the M-neurons) is to ensure the development of a strong isometric contraction of the extensor tibiae muscle, and thus a powerful jump in response to external stimuli. 5. Insofar as the initiation of the locust jump depends on sensory convergence onto large identified interneurons, this behavior is similar to ballistic movements in some other animals such as the crayfish tail flip and the startle response in fish. The unique feature of the locust jump is that the trigger interneurons initiate the jump only after a preceding phase (cocontraction) has been accomplished. PMID- 6247460 TI - An intracellular investigation of cat vesical pelvic ganglia. AB - 1. Intracellular recording techniques were used to study individual neurons in the cat parasympathetic vesical pelvic ganglion (VPG). 2. Active and passive electrical properties were determined from 140 ganglion cells (35 preparations). 3. Three types of ganglion cells were distinguished. Type I (A and B) cells were nonaccommodating cells in response to depolarizing current pulses. Type II cells showed accommodation to depolarizing current pulses. Other cells, presumably glia, were also impaled. 4. Type IB cells exhibited two kinds of nonsynaptic spontaneous activity, spontaneous action potentials (60-70 mV) and small spontaneous potentials (up to 5 mV). Characteristics of the spontaneous activity were examined. 5. The duration of the spikes' afterhyperpolarization resulting from either orthodromic or antidromic train stimulation was dependent on the frequency of train stimulation. No long-lasting posttrain hyperpolarization was observed. 6. Chlorisondamine (10(-6) M), d-tubocurarine (10(-5) M), and hexamethonium (10(-5) M) reversibly blocked orthodromic responses. 7. The VPG is a useful model to study parasympathetic ganglionic transmission at the cellular level. PMID- 6247461 TI - A calcium-activated hyperpolarization follows repetitive firing in hippocampal neurons. AB - 1. A long-lasting afterhyperpolarization (AHP) follows current-induced repetitive firing in hippocampal CA1 neurons studied in vitro. A 10-25% increase in membrane slope conductance occurs during the AHP, suggesting that it may be mediated by an increased conductance to either K+ or Cl-. 2. Intracellular Cl- iontophoresis does not alter the AHP but does attenuate the IPSP. In contrast Ba2+, a cation that can decrease K+ conductance, eliminates the AHP but not the IPSP. These findings suggest the AHP is produced by a long-lasting increased conductance to K+, and is distinct from the IPSP. 3. Mn2+, a Ca2+-channel blocker, eliminates the AHP. In comparison, the AHP persists in the presence of the Na+-channel blocker, tetrodotoxin (TTX), and appears to be temporally associated with TTX resistant "Ca2+ spikes." It is concluded that AHP is probably activated by Ca2+ influx. 4. These observations indicate that the AHP may be produced by a Ca2+ activated K+ current. A balance between cellular depolarization produced by Ca2+ entry and repolarization generated by a Ca2+-activated K+ current appears to operate to control excitability in some mammalian cortical neurons as it does in molluscan neurons. Disruption of this balance by Ba2+ produces spontaneous membrane-potential oscillations and recurrent burst firing in hippocampal neurons. Increases in the magnitude and duration of Ca2+ depolarization and/or decreases in the Ca2+-activated, K+-mediated repolarization may be mechanisms that lead to spontaneous, epileptiform bursting in mammalian cortical neurons. PMID- 6247462 TI - Plasmacytoma of the clivus presenting with an unusual combination of symptoms: case report. AB - A case of plasmacytoma of the clivus is presented. The patient was asymptomatic until a coincidental traumatic lesion produced manifestations of vagus nerve dysfunction. Conduction was blocked in some fibers of the vagus nerve while, at the same time, episodes of activity were triggered in fibers of the same nerve trunk, resulting in an unusual combination of symptoms. The symptomatology of the case is discussed. PMID- 6247463 TI - Cyclic AMP excretion in urines of patients with subarachnoid hemorrhages. AB - Urinary excretion of cAMP was closely monitored for several days in 74 patients with subarachnoid hemorrhages. A rise in urinary cAMP up to 45 microM/24h was observed (normal values being 1 to 5 microM/24h). Patients with associated metabolic disorders were excluded from this study. We have found a correlation between the severity of the clinical conditions, recovery from acute disorder and cAMP excretion, thus suggesting that an increase of urinary cAMP level is related to the extent and the evolution of the acute cerebral damage. PMID- 6247464 TI - Status of gallium-67 in tumor detection. PMID- 6247465 TI - The predictive value of myocardial radioisotope scanning in animals treated with doxorubicin. AB - Thirty-four New Zealand white rabbits were treated with doxorubicin and imaged weekly with Tc-99m pyrophosphate to define the value of abnormal myocardial images in predicting doxorubicin-induced cardiac toxicity. Increased myocardial uptake was detected in most animals on sustained treatment with doxorubicin. A greater proportion of the heart was involved with doxorubicin-related histologic changes in animals with strongly positive myocardial images than in treated animals with moderately positive or normal scans. The myocardial images returned to normal levels 2--6 wk after doxorubicin was discontinued. Five of seven rabbits that received doxorubicin after they had three moderately positive myocardial scans, died from congestive heart failure. Three rabbits whose doxorubicin was discontinued because of scan findings, survived for 6 wk or more before dying from renal failure. The three rabbits who received the highest total dose of doxorubicin died of renal failure without developing abnormal myocardial scans. PMID- 6247466 TI - Receptor-binding radiopharmaceuticals for imaging breast tumors: estrogen receptor interactions and selectivity of tissue uptake of halogenated estrogen analogs. AB - Four halogenated estrogen analogs--o-fluorohexestrol, and 1-fluoro-, 1-bromo-, and 1-iodohexestrol--have been prepared and tritium-labeled in high specific activity, to investigate their potential as estrogen-receptor-based agents for imaging breast tumors. These compounds bind with high affinity in vitro to the cytoplasmic uterine estrogen receptor from rat and lamb and sediment as 8S receptor complexes on sucrose gradients. After 1 hr in immature rats, these compounds show high uptake into the uterus, but low uptakes (10--25% of the uterine levels) into most nontarget tissues. The uterine uptake is estrogen specific since it is depressed by excess nonradioactive estradiol. Uptake selectivity is greatest for the fluorohexestrols and decreases for the bromo and iodo compounds. In mature rats bearing DMBA-induced mammary tumors, selective uptake by the uterus and tumors is seen with 1-fluoro[3H4]hexestrol and o fluoro[3H3]hexestrol. The studies indicate that these four halogenated hexestrols are promising candidates as estrogen-receptor-based agents for the imaging of human breast tumors. PMID- 6247467 TI - The search for a gamma-emitting estrogenic ligand. PMID- 6247468 TI - Effects of several types of dietary fibers on lipid content in liver and plasma, nutrient retentions and plasma transaminase activities in force-fed growing chicks. PMID- 6247469 TI - Bile salt adsorption ability of dietary fiber from named varieties of carrot at different developmental ages. AB - The adsorption of bile salts to fiber has been measured using fiber prepared from different varieties of carrot at different developmental ages. We investigated the carrot varieties Altrinchan and Chantenay and used the bile salts deoxycholate and glycocholate. The method used to measure adsorption distinguished between true adsorption and apparent adsorption due to bile salts trapped within the interstices of the fiber matrix. Adsorption ability was influenced by the developmental age of the carrot but not by variety. Adsorption ability was at a maximum when the carrot fresh weight was at a maximum. The adsorption ability measured was true adsorption and was not dependent on the water holding capacity of the fiber. Deoxycholate was better adsorbed than glycocholate and the results suggest that the developmental age of a fiber source could be important when formulating diets designed to influence bile salt metabolism. PMID- 6247470 TI - Effect of dietary wheat bran, alfalfa, pectin and carrageenan on plasma cholesterol and fecal bile acid and neutral sterol excretion in rats. PMID- 6247471 TI - Absence of airway hyperreactivity to methacholine in a worker sensitized to toluene diisocyanate (TDI). AB - A worker with occupational asthma due to toluene diisocyanate (TDI) was studied. Detailed immunologic studies, including those for p-tolyl isocyanate IgE antibodies and the presence of leukocyte inhibition factor for isocyanate antigen, were negative. Clinically, the subject noted more pronounced symptoms beginning on Monday morning, followed by weekend off work, and lessening of her symptoms over the working week. Methacholine challenges were negative when performed on three separate occasions, including the time when maximum symptoms were present, and again six months later, before and after bronchial challenge testing. A dose-related response to TDI was observed on bronchial provocation testing using nonirritating concentrations of TDI of 0.0165 and 0.030 ppm. This case provides evidence that the response of the airway to TDI may not always be accompanied by hyperreactivity to methacholine. Screening programs utilizing methacholine challenges may not always identify sensitized workers, since a negative methacholine challenge test does not exclude TDI sensitization. PMID- 6247472 TI - Active and passive renal sodium reabsorption. PMID- 6247473 TI - Chronic rotavirus infection in immunodeficiency. AB - The characteristics of rotavirus infection in 23 children with a variety of primary immunodeficiency diseases were studied. Stools and sera were tested for rotavirus by means of the enzyme-linked immunosorbent assay and the enzyme-linked fluorescent assay, respectively. Four immunodeficient patients had diarrhea during the study period and all had rotavirus infection; rotavirus was not detected in the stools of the 19 asymptomatic immunodeficient patients. Forty-six control children with diarrhea were tested and 22 had rotavirus infection; rotavirus was not detected in 39 asymptomatic control children. One immunodeficient patient with X-linked agammaglobulinemia and one with severe combined immunodeficiency had chronic, symptomatic rotavirus infection with rotavirus excretion lasting more than six weeks. The other two immunodeficient patients and eight control children eliminated the rotavirus from their stools in periods ranging from two to 12 days. Rotavirus antigen was detected in the sera of three of the four immunodeficient patients; none of the 14 control infants tested had rotavirus antigen detected in their sera. This study indicates that rotavirus may produce a chronic infection in immunodeficient children. PMID- 6247474 TI - DNA fingerprinting in investigation of apparent nosocomial acquisition of neonatal herpes simplex. PMID- 6247475 TI - Growth patterns, ultrastructure, and chromosomal constitution of normal kidney and nephroblastoma cells in short-term culture. AB - Nephrectomies were performed on four children with nephroblastomas (Wilms' tumor). Tumor tissue and normal kidney tissue were taken from each patient and were cultured. The in vitro characteristics of the cultured cells were then compared with their known in vivo characteristics. The normal kidney cells showed uniform cell morphology, had a relatively slow and orderly growth pattern and had the usual diploid chromosomal constitution. The tumor cells on the other hand were irregular in morphology and had a rapid and disorderly growth pattern. Electron microscopic examination confirmed the variation in the tumor cell morphology. In addition, microfilaments were seen to be abnormally abundant in many of the cells and some cells contained membrane-bound granules. Desmosomes were absent. Chromosome analyses showed cells from three of the nephroblastoma samples to maintain a constant hyperdiploid karyotype during the first few passages in vitro, whereas the normal kidney cells continued to have the normal diploid karyotype. Our study suggests that nephroblastoma and normal kidney cells are stable in culture, that is they retain most of their cellular characteristics in vitro and do not undergo rapid dedifferentitation in short-term culture. PMID- 6247476 TI - Sonicated and passively dispersed hydrogen peroxide in periodontitis. PMID- 6247477 TI - Effect of hyperthermically elevated serum prolactin on epididymal cyclic AMP (adenosine 3',5'-cyclic monophosphate) levels in rats. PMID- 6247478 TI - Mode of action of sesquiterpene lactones as anti-inflammatory agents. AB - Sesquiterpene lactones containing an alpha-methylene-gamma-lactone moiety were shown to be potent inhibitors of carrageenan-induced edema and chronic adjuvant induced arthritis in rodents at 2.5 mg/kg/day. The mode of action of sesquiterpene lactones as anti-inflammatory agents appeared to be at multiple sites; for example, at 5 X 10(-4) M, the sesquiterpene lactones effectively uncoupled the oxidative phosphorylation of human polymorphonuclear neutrophils and elevated the cyclic adenosine monophosphate levels of rat neutrophils and rat and mouse liver cells. Free and total lysosomal enzymatic activity was inhibited by these agents at 5 X 10(-4) M in both rat and mouse liver and rat and human neutrophils. Furthermore, the structure-activity relationships for the stabilization of lysosomal membrane for rat liver cathepsin activity followed the same structural requirement necessary for anti-inflammatory activity; i.e., the alpha-methylene-gamma-lactone moiety contributed the most activity, whereas the beta-unsubstituted cyclopentenone and alpha-epoxycyclopentanone contributed only minor activity. Human polymorphonuclear neutrophil chemotaxis was inhibited at low concentrations (i.e., 5 X 10(-5) and 5 X10(-6) M), whereas prostaglandin synthetase activity was inhibited at a higher concentration (i.e., 10(-3) M) by the sesquiterpene lactones. PMID- 6247479 TI - Spontaneous fluctuations of potassium channels in the apical membrane of frog skin. AB - 1. The previously demonstrated K+-dependent short-circuit current through the skin of frog species Rana temporaria (Zeiske & Van Driessche, 1979), bathed with mucosal K+- and serosal Na+-Ringer solution, was investigated with current fluctuation analysis. 2. The current-noise spectra were recorded in the frequency range from 1 to 800 Hz and showed a Lorentzian component with a mean plateau value S0 = (1.50 +/- 0.05).10(-20) A2.s.cm-2 and a corner frequency of fc=(81.0 +/- 3.4)Hz(n=14). 3. S0 increased with mucosal K+ concentration, [K]o, while fc remained almost unchanged. A decrease in S0 was observed when serosal Na+ was replaced by K+. 4. Mucosal Cs+ (10 mM) depressed, reversibly, the K+-dependent current noise to the level of the background noise. Moreover, a linear decrease in fc with increasing Cs+ concentration was observed. 5. Among the other tested alkali cations, Rb+ was the only blocker though less potent than Cs+. Tetraethylammonium, 4-aminopyridine, 2.4.6-triaminopyrimidine and amiloride had no effect. 6. Alterations in the transcellular transport of Na+ contained in a mucosal solution with high [K]o resulted in significant changes in K+ current noise. 7. The current-fluctuation intensities decreased with increasing contact time to high [K]o; these changes were concomitant with the previously reported time dependence of the short-circuit current (Zeiske & Van Driessche, 1979). 8. The K+-dependent fluctuations are thought to originate from K+-selective pathways in the apical cell membranes. The description of the K+-current noise by a single Lorentzian suggests that the "K+ channels" switch randomly between an open and closed state. 9. Assuming a two state model for the channel-kinetics, the single channel current i and the channel density M were calculated as i=(0.37 +/- 0.05)pA and M=(0.53 +/- 0.08) mu-2 (n=13). PMID- 6247480 TI - Nickel and calcium ions modify the characteristics of the acetylcholine receptor channel complex at the frog neuromuscular junction. AB - 1. Miniature end-plate currents (m.e.p.c.s) and acetylcholine induced current noise were recorded from the cutaneous pectoris muscle of the frog with the voltage-clamp technique. Analysis of current noise was used to estimate mean single channel current and the mean lifetime of an open channel. 2. Adding Ni2+ or Ca2+ to the bathing solution reduced the amplitude of the m.e.p.c.s. Ten mM Ni2+ decreased the amplitude 64%, while raising Ca2+ from 2 to 10mM decreased the amplitude 35%. 3. The decreased amplitude of the m.e.p.c. in Ni2+ and increased Ca2+ can be explained by a decrease in single channel current. Ten mM-Ni2+ decreased mean single channel current 64% while raising Ca2+ from 2 to 10 mM decreased single channel current 28%. 4. The decrease in single channel current was due to a decrease in the driving potential and single channel conductance. Ten mM-Ni2+ and Ca2+ shifted the reversal potential for the m.e.p.c. about 10 mV negative from the control value of -4.6 mV; at the same time single channel conductance was decreased 59% in Ni2+ and 18% in increased Ca2+. 5. In contrast to the similar direction of effects of Ni2+ and Ca2+ on m.e.p.c. amplitude, reversal potential, and single channel conductance, Ni2+ and Ca2+ had different effects on m.e.p.c. time course. Ten mM-Ni2+ increased the time constant of m.e.p.c. decay 80% while raising Ca2+ from 2 to 10 mM decreased the time constant of decay 17%. 6. Ni2+ and Ca2+ also had different effects on single channel lifetimes. Ten mM-Ni2+ increased channel lifetime about 50%, while raising Ca2+ from 2 to 10 mM did not significantly affect channel lifetime. 7. These results suggest that changes in single channel lifetime and conductance due to ionic influences are not necessarily tightly coupled. The results also suggest that the effects of both Ni2+ and Ca2+ on channel lifetime cannot be accounted for in terms of a simple surface potential hypothesis. PMID- 6247481 TI - The equilibrium between different conformations of the unphosphorylated sodium pump: effects of ATP and of potassium ions, and their relevance to potassium transport. AB - 1. Changes in the intrinsic fluorescence of Na, K-ATPase protein have been used to monitor the interconversion of E(1) (low fluorescence) and E(2) (high fluorescence) forms of the unphosphorylated enzyme.2. In media lacking sodium and nucleotides, 1 mM-potassium was sufficient to convert practically all of the enzyme into the E(2) form. In media containing 1 mM-potassium, 1 mM-EDTA, and no sodium or magnesium, the addition of ATP, or its beta, gamma-imido or methylene analogues, converted the enzyme back into the E(1) form. The relation between nucleotide concentration and the fraction of the enzyme that was in the E(1) form could be described by a rectangular hyperbola, with a K((1/2)) of about 15 muM for ATP, 65 muM for adenylyl-imidodiphosphate (AMP-PNP) and 180 muM for adenylyl (beta, gamma-methylene)-diphosphonate (AMP-PCP). ADP also converted the enzyme back into the E(1) form, with a K((1/2)) of about 25 muM, but the relation between concentration and fraction converted was not well described by a rectangular hyperbola.3. In similar media containing 50 mM-potassium, much higher concentrations of ATP were required to convert the enzyme back into the E(1) form, and the conversion was probably incomplete.4. If we assume that ATP and potassium ions affect each other's binding solely by altering the equilibrium between E(1) and E(2) forms of the enzyme, we are able to conclude (i) that potassium ions bind to the E(1) form with a moderately low affinity, (ii) that, in the absence of nucleotides, the equilibrium between E(1)K and E(2)K is poised strongly in favour of E(2)K, (iii) that the binding of ATP to a low-affinity site alters the equilibrium constant for the interconversion of E(1)K and E(2)K by two to three orders of magnitude, so that, at saturating levels of ATP, the equilibrium is probably slightly in favour of E(1)K, and (iv) that in sodium free, potassium-containing media, ATP will appear to bind to the enzyme more tightly than would be expected from the dissociation constant of the E(2)K. ATP complex.5. The pattern of the equilibrium constants for the various reactions between E(1), E(2), ATP and potassium is compatible with the hypothesis that the ATP-accelerated conversion of E(2)K into E(1)K, and the subsequent release of potassium ions from low-affinity inward-facing sites, are part of the normal sequence of events during potassium influx in physiological conditions. PMID- 6247482 TI - Binding of scorpion toxin to sodium channels in vitro and its modification by beta-bungarotoxin. AB - 1. Binding of a purified scorpion toxin to membrane fragments isolated from electroplaque of an electric eel Electrophorus electricus was studied using a radio-iodinated toxin.2. A scorpion toxin was purified from the venom of Leiurus quinquestriatus and iodinated with (125)I in a lactoperoxidase-catalysed reaction. Monoiodinated toxin, isolated by an ion exchange chromatography, retarded the inactivation kinetics of Na current to a similar extent as the native toxin, indicating that radioiodination did not appreciably affect physiological and binding properties of the native toxin.3. Analyses of binding properties by Scatchard plots showed the presence of two classes of binding sites (with low and high affinities) in the membrane preparation from eel electroplaque; similar preparation from an electric skate, of which the electroplaque is known to be devoid of Na channels, possessed only the low affinity sites.4. The number of high affinity sites in the eel preparation was 41.8 +/- 10.5 p-mole/g tissue; the value was within the range reported for tetrodotoxin binding to similar preparations (15-148 p-mole/g tissue).5. A variety of cations (Na(+), Mn(2+) and La(3+)) inhibited the high affinity scorpion toxin binding, as indicated for the toxin binding to Na channels by a previous electrophysiological study. K(D) value in the presence of 120 mM-Na(+) (approx. 8 nM) agreed reasonably with that (approx. 10nM) reported for the scorpion toxin binding to excitable neuroblastoma cells or synaptic nerve ending particles under conditions where membrane potential was depolarized by the addition of 135 mM-KCl.6. Pretreatment of the eel membrane preparation with beta bungarotoxin (7-44 ng/ml.) in the presence of Ca ions (10-200 muM) resulted in a substantial loss of high affinity binding of scorpion toxin. When phospholipase A(2) activity of the beta-toxin was inactivated by a chemical modification with p bromophenacyl bromide, the inhibitory action of the beta-bungarotoxin was abolished.7. It is concluded that a high affinity binding of scorpion toxin to the eel electroplaque membrane fragments represents the binding to Na channels in vitro, and that phospholipase A(2) activity of beta-bungarotoxin interferes with the binding of scorpion toxin to Na channels. PMID- 6247483 TI - The relationship between muscarinic receptor binding and ion movements in rat parotid cells. AB - 1. The relationship of muscarinic receptor binding to ion fluxes induced by muscarinic agonists was investigated in rat parotid cells. 2. Receptor binding was measured with [3H]quinuclidinyl benzilate in living, dispersed parotid acinar cells. These same cells were used to determine concentration-effect relationships (ion fluxes) for agonists. 3. Receptor binding of antagonists accurately reflected the pharmacologically determined affinities. In the case of agonists, apparent pharmacological affinities were greater than binding affinities by a factor of 12.5 for methacholine and 18.7 for carbachol. 4. The reason for the discrepancy between agonist binding and effect is not known with certainty, but the existence of "spare" receptors is considered a possibility. 5. The total number of muscarinic receptors is estimated to be 23,000/cell. If some are spare, as few as 1800/cell may suffice to fully activate the available Ca channels. PMID- 6247484 TI - Relations between the inactivation of sodium channels and the immobilization of gating charge in frog myelinated nerve. AB - 1. Single, voltage-clamped nerve fibres of Rana esculenta were stimulated with ;P/2' pulse patterns for measuring Na and gating currents at 13 degrees C.2. Gating currents during test pulses to - 122 or + 10 mV were measured after 45 msec conditioning steps to voltages between - 122 and - 18 mV. As the conditioning voltage was made more positive than - 80 mV, the movable gating charge diminished along a sigmoid curve, approaching a value of nearly one third of the maximum charge. On the other hand, Na inactivation began at a more negative potential and proceeded to undetectable levels.3. After a depolarizing prepulse, both time constant and size of the charge movment depended less steeply on the test voltage than normally. The prepulse reduced gating currents associated with steps from - 122 to test voltages >/= - 40 mV, but enhanced gating currents obtained with test voltages < - 40 mV.4. Increasing the duration of a depolarizing pulse (- 54 to + 42 mV) reduced the fast ;off' gating current at the end of the pulse and enhanced a slow component. Their total charge corresponded approximately to that carried during the pulse. During depolarization, Na current inactivated in a fast and a slow phase. The fast phase was also reflected in the loss of fast charge movement (immobilization) as seen after the pulse was interrupted at various durations.5. The available Na current and the fast movement of gating charge diminished in parallel during prepulses more positive than - 54 mV, and recovered in parallel upon repolarization to levels between - 102 and - 46 mV. During prepulses between - 62 and - 78 mV, however, Na inactivation occurred up to 4 times faster than charge immobilization. Also, at - 78 mV, Na current was inactivated 3 times faster than it recovered.6. These findings indicate that Na inactivation and charge immobilization are linked, but proceed with high-order kinetics. The simplest scheme that accounts for their relation is [Formula: see text] Depending on voltage, either state h(2) (E > - 45 mV) or h(3) (E < - 45 mV) becomes kinetically undetectable.7. A model of the Na channel is developed in which inactivation gains most of its voltage dependence by a coupling to the fast charge movement (activation). The model is shown to be quantitatively consistent with the results. In particular, the change of kinetics observed near - 45 mV can be explained as an effect of the redistribution of charges on the inactivation process. PMID- 6247485 TI - The release of acetylcholine from post-ganglionic cell bodies in response to depolarization. AB - 1. Acetylcholine (Ach) release from parasympathetic ganglia cell somata was investigated in denervated avian ciliary ganglia. Three days after the input to the ganglion (the oculomotor nerve) was sectioned, all presynaptic nerve terminals had degenerated. 2. Denervated ganglia were shown to contain endogenous ACh and to be capable of synthesizing [3H]ACh from [3H]choline added to the incubation medium. 3. In response to depolarization induced by incubation in 50 mM-[K+]o, denervated ganglia released [3H]ACh into bath effluents in amounts approximately 15% of the non-denervated contralateral control. This release was shown to be Ca2+ dependent in both intact and denervated ganglia. 4. Antidromic electrical stimulation of ciliary nerves also elicited [3H]ACh release. Nicotine (1 microgram/microliter.) depolarized denervated ciliary ganglion cells and evoked release of the transmitter and this release was antagonized by curare. 5. It is concluded that the ganglionic cell bodies sysnthesized ACh and released the transmitter in response to K+ depolarization, antidromic stimulation and cholinergic agonists, despite the lack of morphological specializations usually associated with stimulus-induced release of neurotransmitter. The evidence suggests the existence of a mechanism of transmitter release which is Ca2+ dependent, probably from a cytoplasmic pool and therefore distinct from the usual vesicular release at the nerve terminal. PMID- 6247487 TI - Transmitter induced calcium entry across the post-synaptic membrane at frog end plates measured using arsenazo III. AB - 1. The Ca2+ influx occurring across the post-synaptic membrane during transmitter action was studied at the frog neuromuscular junction, using the Ca sensitive dye arsenazo III to monitor the resulting changes in free myoplasmic Ca2+ concentration. 2. Calibration experiments showed a linear relationship between the amount of Ca2+ injected by ionophoresis into a muscle fibre, and the peak size of the arsenazo light absorbance record. 3. Ionophoretic application of acetylcholine (ACh) to voltage clamped end-plates gave rise to an arsenazo signal. The size of this response varied with the Ca2+ concentration in the bathing solution. 4. The arsenazo light response increased in size steeply, and non-linearly, with hyperpolarization of the end-plate membrane, even when the end plate current increased approximately linearly with hyperpolarization. The voltage dependence of the light response could be fitted well by an exponential with a voltage constant of 28 mV. Changes in Ca2+ concentration of the bathing medium had little effect on this relationship. 5. At end-plates bathed in isotonic CaCl2 solution the voltage dependence of both the arsenazo light response, and the end-plate current showed a closely similar, non-linear relationship. 6. Addition of 12 mM-Co2+ to a bathing solution initially containing 12 mM-Ca2+ substantially reduced the size of the arsenazo light response, and the voltage dependence of this response became more linear. 7. Arsenazo light responses were also recorded in response to transmitter release evoked by nerve stimulation. The size of the nerve evoked light response showed a non-linear voltage dependence, whilst the end-plate current was a linear function of membrane potential. PMID- 6247488 TI - Saxitoxin binding to sodium channels of rat skeletal muscles. AB - 1. The saturable binding of exchange-labelled tritiated saxitoxin (STX) to the extensor digitorum longus (e.d.l.), diaphragm and soleus muscles of adult rats was studied. By measuring STX uptake to small pieces of muscle, the dissociation constant (KD) and binding capacity could be determined for individual muscles. 2. The affinity for STX is very similar in all three muscles, with a KD of 4.3 +/- 0.3, 5.1 +/- 0.5 and 4.9 +/- 0.5 nM (mean +/- S.E. of mean) at 4 degrees C for e.d.l., diaphragm and soleus respectively. The maximum binding capacity, which varies between different muscles, is 52.6 +/- 2.5, 40.3 +/- 4.9 and 23.8 +/- 1.1 f-mole.mg wet wt.-1 respectively. 3. The affinity of e.d.l. for tetrodotoxin (TTX), measured by inhibition of STX binding, is 12.1 +/- 1.4 nM at 4 degrees C. Raising the temperature to 37 degrees C increases the KD for STX to 6.8 +/- 0.8 nM and the KD for TTX to 47.5 +/- 4.5 nM. 4. STX binding is pH dependent; protons compete with STX for the binding site as if there were a titratable acidic group with a pK of 5.5. 5. The binding capacity of the diaphragm is not uniform along the length of the muscle fibres. Binding at the ends of the fibres is only 78% of that in the central region. 6. Denervation of e.d.l. for 7 days causes no change in the affinity for STX. There is a slight reduction in the binding capacity from 54 +/- 5 to 43 +/- 3 f-mole.mg wet wt.-1. There is no change in the diameter of the muscle fibres. PMID- 6247486 TI - Aequorin response facilitation and intracellular calcium accumulation in molluscan neurones. AB - 1. When molluscan neural somata are filled with the calcium-indicating photo protein aequorin and subjected to a 1 Hz train of depolarizing pulses (0.3 sec duration to + 15 mV) under voltage clamp, the successive photo-emissions due to calcium influx facilitate. The origin of this phenomenon was investigated in identified neurones from the abdominal ganglion of Aplysia californica.2. Since outward currents inactivate cumulatively in successive pulses, the effective depolarization increases due to a series resistance error. Elimination of this error by electronic compensation or pharmacological block of outward current reduced aequorin response facilitation by only about 30%, on the average.3. When voltage-dependent sodium and potassium currents are blocked in tetraethylammonium (TEA)-substituted zero-sodium sea water, the remaining inward calcium currents display no facilitation. On the contrary, a slow decline during a pulse and a slight progressive depression in successive pulses are observed. Barium substitution for calcium in the same medium eliminates a small residual potassium current insensitive to external TEA. The remaining inward barium currents also display depression instead of facilitation.4. A non-pharmacological separation of calcium current was accomplished by measuring tail currents at the potassium equilibrium potential following depolarizing pulses. Calcium tail currents activate rapidly and then decline gradually and incompletely as depolarizing pulse duration is lengthened. Tail currents also show no evidence of facilitation; there is instead a slight depression of currents after successive pulses.5. Increments of optical absorbance in neurones filled with the calcium sensitive dye arsenazo III show a depression rather than facilitation to successive depolarizations in a train. The time course of these absorbance signals is consistent with the time-dependent depression of calcium current.6. Calibration of arsenazo III response amplitude indicates that the dye reports only about 1% of the calcium concentration increment expected from knowledge of cell volume and the charge carried by calcium current during a depolarizing pulse. This suggests that cytoplasmic buffering of free calcium must occur rapidly, on a time scale comparable to the response time of arsenazo III (about 1 msec) or more rapidly.7. The slow potassium tail current following a depolarizing pulse is calcium-dependent and probably provides an approximate index of the internal sub-membrane calcium concentration. Increments in this current after repetitive pulses display a slight progressive depression rather than facilitation.8. Since neither calcium currents nor the concentration transients show facilitation, we conclude that aequorin response facilitation is due to the non-linear dependence of aequorin photo-emissions on calcium concentration. This conclusion is supported by a finding that the very different kinetics of arsenazo III responses and aequorin responses can be reconciled by a simple model representing calcium accumulation and known response properties of the two indicator substances.9. In a train of impulses evoked by injecting depolarizing current into a neurone, the successive action potentials grow in duration. Nevertheless, a nearly constant calcium influx signalled by arsenazo III accompanies broadening action potentials. PMID- 6247489 TI - Synthesis of syn and anti isomers of 6-[[(hydroxyimino)phenyl]methyl]-1-[(1 methylethyl)sulfonyl]-1H-benzimidazol-2-amine. Inhibitors of rhinovirus multiplication. AB - The synthesis and antirhinovirus activity of syn and anti isomers of 6 [[(hydroxyimino)phenyl]methyl]-1-[(1-methylethyl)sulfonyl]-1H-benzimidazol-2 amine (4 and 5) are reported. The structural assignments of 4 and 5 are based upon 13C NMR spectra of both isomers and also X-ray analysis of 5. The anti isomer 5 was more potent than the syn-isomer 4 when compared as an inhibitor of rhinovirus multiplication in vitro. Both isomers inhibited multiplication of 15 different serotypes of rhinovirus. PMID- 6247490 TI - Synthesis of some new S-alkylated derivatives of 5-mercapto-2'-deoxyuridine as potential antiviral agents. AB - A series of S-alkylated derivatives of 5-mercapto-2'-deoxyuridine have been prepared by alkylation of the preformed nucleoside. Two of these compounds, the S propargyl and S-allyl derivatives, have shown significant antiviral activity against Herpes simplex type 1 in HeLa TK- cells but appear to be less effective in this assay system than some previously reported 5-substituted 2' deoxyuridines. PMID- 6247491 TI - Immunosuppression in toxoplasmosis: further studies on mice infected with louping ill virus. AB - Mice were infected with an avirulent cyst-producing strain of Toxoplasma gondii and given injections of louping-ill virus 7 days later; control mice were given virus but not Toxoplasma. Test and control mice were then killed, in groups, 2, 4, 6, 8 and 10 days later. In the dually infected mice viraemia was later, greater and more prolonged; titres of virus recovered from brain and spleen were greater; production and haemagglutinating antibody to louping-ill virus was later and less, and inflammation in the brain was more severe, than in mice given virus alone. We suggest that T. gondii suppressed the immunity of mice, making them more susceptible to the virus, and that a significant proportion of the increased number of inflammatory cells observed in the brain could have been toxoplasma specific and not virus-specific and hence contributed to the increased susceptibility of the dually infected mice to louping-ill virus. PMID- 6247492 TI - Antibiotic inhibition of protease production by Pseudomonas aeruginosa. AB - The effects of tetracycline, chloramphenicol and polymyxin B on growth and protease production by Pseudomonas aeruginosa were studied. Tetracycline inhibited protease production at concentrations much lower than those required to cause growth inhibition; the effect was not due to inhibition of protease activity by the antibiotic. In contrast, chloramphenicol and polymyxin B inhibted protease production in direct proportion to the inhibition of growth. Lysozyme release experiments with washed tetracycline-treated cells indicated that the protease did not accumulate intracellularly. The protease-inhibiting effect of tetracycline might have therapeutic significance if it were found to occur in vivo. PMID- 6247494 TI - Water and salt permeability of gastric vesicles. PMID- 6247493 TI - Effects of calcium, lanthanum, and temperature on the fluidity of spin-labeled human platelets. AB - Previous platelet studies have shown that calcium plays important roles in stimulus-secretion coupling, aggregation, and other membrane-associated functions. In addition, lanthanum induces platelet aggregation and the platelet release reaction and also influences platelet responsiveness to various stimuli. The spin-label results presented here suggest that one mechanism through which calcium and lanthanum mediate their effects on platelet functions may be by decreasing the lipid fluidity of the surface membrane. The structure of platelet membrane lipids was examined with the spin-label method. Washed human platelets were labeled with the 5-, 12- and 16-nitroxide stearic acid spin probes. Order parameters which measure the fluidity of the lipid environment of the incorporated probe may be calculated from the electron spin resonance (ESR) spectra of 5-nitroxide stearate [I(12,3)]-labeled cells. Evidence is presented which indicates that these spectra principally reflect properties of the platelet surface membrane lipids. The membrane fluidity increased with temperature for the range 17 to 37 degrees C. Either calcium or lanthanum additions to intact cells increased the rigidity of the platelet membranes at 37 degrees C, although the La3+ effect was larger and occurred at lower concentrations than that of Ca2+. For example, addition of 1 mM La3+ or 4 mM Ca2+ increased the order parameter of I(12,3)-labeled platelets by 4.3 +/- 1.7% or 2.1 +/- 0.5%. Preliminary studies conducted on purified platelet plasma membranes labeled with I(12,3) indicated that 1 mM LaCl3 or 4 mM CaCl2 additions similarly decreased the lipid fluidity at 37 degrees C. The above cation-induced effects on the fluidity of whole platelets were reversed by the use of the divalent cation-chelating agent ethylene glycol bis-(beta-aminoethyl ether)-N,N'-tetra-acetic acid (EGTA). Lastly, lanthanum (0.2 1 mM) caused rapid aggregation of platelets which were suspended in a 50-mM Tris buffer pH 7.4 that did not contain adenosine. PMID- 6247495 TI - Some characteristics of Na/K-ATPase from rat intestinal basal lateral membranes. AB - Basal lateral membrane vesicles were isolated from rat intestinal epithelial cells. The sodium potassium triphosphatase (Na/K-ATPase) of these plasma membranes has been characterized by (1) the molecular weight of the phosphorylated intermediate, (2) the sensitivity of the phosphorylated intermediate to hydroxylamine, (3) its ouabain binding constants, and (4) its susceptibility to digestion by pronase. The phosphorylated intermediate was shown by SDS polyacrylamide gel electrophoresis to be a protein of 100,000 Daltons apparent mol wt. Its extensive hydrolysis in hydroxylamine demonstrated that it was an acyl phosphate. The isolated basal lateral membranes bound ouabain with a dissociation constant, Km (1.5 x 10(5) M), similar to the inhibitory constant KI (3 X 10(-5) M), measured for ouabain inhibition of the Na/K-ATPase activity. The association rate constant measured for ouabaiation rate constants reported for other tissues and species. The high dissociation rate constant 3.6 x 10(-2) sec 1, is consistent with the insensitivity of the rat to ouabain. Digestion of the intact cells by pronase yielded basal lateral membranes in which the Na/K-ATPase had been unaffected. The phosphorylated intermediate ran as a sharp band at 100,000 Daltons on electrophoresis, and the ouabain dissociation constant appeared to be unchanged. In these membranes, protein stains of polyacrylamide gels revealed digestion of the major high mol wt proteins including the major protein at 100,000 Daltons. This suggests that the Na/K-ATPase represents a minor component, less than 1%, of the basal lateral membrane protein. From these characteristics of the phosphorylated intermediate and the ouabain binding constants, we conclude that the Na/K-ATPase of the basal lateral membranes of rat intestinal epithelial cells is similar to that found in other tissues and species. Estimates of the number of pump sites and the turnover number predict rates of Na transport that are consistent with observed values. PMID- 6247496 TI - A technique for preparing non-degraded rRNA from adult mammalian isolated heart muscle cells. PMID- 6247497 TI - Structural and functional characteristics of isolated thyroid follicles. PMID- 6247498 TI - Expression of early and late simian virus 40 transcripts in the absence of protein synthesis. AB - We examined the synthesis of early and late simian virus 40 (SV40) mRNA's in SV40 infected cells treated with two kinds of protein synthesis inhibitors. SV40 stimulated the synthesis of mRNA's for both large and small tumor antigens in cells pretreated with the drug emetine before the addition of virus. Emetine is a stringent inhibitor of protein synthesis and, thus, protein factors necessary for transcription and processing of these mRNA's probably preexist in the cell. Surprisingly, infection of cells pretreated with the protein synthesis inhibitor cycloheximide stimulated the synthesis of about 10-fold-higher levels of early viral mRNA's than did comparable infections of nontreated cells. This amplification of early viral mRNA steady-state levels is probably not due to inhibition of synthesis of the early A gene product since the same degree of drug specific amplification was seen in SV40 tsA-infected cells that were cultured at the nonpermissive temperature. However, the most interesting effect of cycloheximide addition on viral mRNA synthesis was its stimulation of the appearance of late mRNA's in the cytoplasm of cells at early periods of infection. The synthesis of late mRNA's does not appear to require the A gene product as late RNAs can be found in the cytoplasm of cells infected with SV40 tsA mutants which have been maintained at 41 degrees C and continuously cultured in the presence of cycloheximide. PMID- 6247499 TI - Gene expression of herpes simplex virus. II. UV radiological analysis of viral transcription units. AB - The transcriptional organization of the genome of herpes simplex virus type 1 was analyzed by measuring the sensitivity of viral polypeptide synthesis to UV irradiation of the infecting virus. Herpes simplex virus type 1 was irradiated with various doses of UV light and used to infect xeroderma pigmentosum fibroblasts. Immediate early transcription units were analyzed by having cycloheximide present throughout the period of infection, removing the drug at 8 h postinfection, and pulse-labeling proteins with [35S]methionine. Delayed early transcription units were analyzed in similar studies by having 9-beta-D arabinofuranosyladenine present during the experiment to block replication of the input irradiated genome. The viral polypeptides were separated by gel electrophoresis and quantitated by densitometry of the gel autoradiograms. The following results were obtained. (i) The UV target sizes for the viral transcription units analyzed ranged from 1.44 to 5.65 kilobase pairs. This implies that the corresponding primary transcripts have minimum molecular weights ranging from 0.46 x 10(6). (ii) The genes for the four viral proteins, 165, 145, 116, and 71 (molecular weight x 10(3), exhibited UV target sizes that agree with their calculated gene size or measured mRNA size or both and thus must reside in promoter-adjacent positions. (iii) The transcription units for the remaining genes analyzed showed target sizes that range from 0.42 to 2.59 kilobase pairs greater than needed to encode the respective proteins. This probably is a reflection of their distances from promoters or the presence of intervening sequences or both. It further suggests that these genes are transcribed as precursor RNA molecules that are larger than their mRNA's. (iv) The results indicate that none of the immediate early genes analyzed can be cotranscribed, whereas some of the delayed early genes might be cotranscribed. No evidence was found for the existance of large, multigene transcription units. PMID- 6247500 TI - Relationship between integrated and nonintegrated viral DNA in rat cells transformed by polyoma virus. AB - Fischer rat fibroblasts transformed by polyoma virus contain, in addition to viral sequences integrated into the host genome, nonintegrated viral DNA molecules, whose presence is under the control of the viral A gene. To understand the mechanism of production of the "free" viral DNA, we have characterized the DNA species produced by several rat lines transformed by wild-type virus or by ts a polyoma virus and compared them with the integrated viral sequences. Every cell line tested yielded a characteristic number of discrete species of viral DNA. The presence of defectives was a very common occurrence, and these molecules generally carried deletions mapping in the viral "late" region. The production of multiple species of free viral DNA was not due to heterogeneity of the transformed rat cell population, and its pattern did not change upon fusion with permissive mouse cells. Analysis of the integrated viral DNA sequences in the same cell lines showed, in most cases, a full head-to-tail tandem arrangement of normal-size and defective molecules. The free DNA produced by these lines faithfully reflected the integrated species. This was true also in the case of a cell line which contained a viral insertion corresponding to approximately 1.3 polyoma genomes, with each of the repeated portions of the viral DNA molecule carrying a different-size deletion. These results support the hypothesis that the free DNA derives from the integrated form through a mechanism of homologous recombination leading to excision and limited replication. PMID- 6247501 TI - Heterogeneity of the genome-linked protein of foot-and-mouth disease virus. AB - The genome-linked protein of foot-and-mouth disease virus was examined by electrofocusing in polyacrylamide gels. Two proteins of different charge and amino acid composition were found. The tryptic peptide maps of the proteins were dissimilar. The possible relationship between the two proteins is discussed. PMID- 6247502 TI - Use of [125I]deoxycytidine to detect herpes simplex virus-specific thymidine kinase in tissues of latently infected guinea pigs. AB - The footpad skin and the lumbosacral dorsal root ganglia were removed from inbred guinea pigs at different times after subcutaneous infection with herpes simplex virus type 2 (HSV-2) in both hind footpads. These tissues, shown by our previous study to harbor latent HSV, were dispersed into single cells. The presence of virus-specific thymidine kinase (TK) in these cells was assayed by the uptake and phosphorylation of [125I]deoxycytidine in culture. [125I]deoxycytidine was shown to be a specific substrate for the HSV-coded TK. The method could detect herpes TK activity in a culture of 10(6) cells with less than 0.1% of the cells being virally infected. The enzyme was readily detected in footpad cells of acutely (24 h) but not of latently (14 days to 1 year) infected guinea pigs. No herpes TK was found either in the sensory ganglionic cells of guinea pigs during the early and late phases of latent infection. It is concluded that HSV-2, while residing in the footpads and the lumbosacral ganglia of the guinea pig during latent infection, does not express any viral TK function. PMID- 6247503 TI - Relationship among Tau antigens isolated from various lines of simian virus 40 transformed cells. AB - In addition to the virus-specified tumor antigens, simian virus 40-transformed cells contain at least one other protein which can be immunoprecipitated with serum from animals bearing simian virus 40-induced tumors. This protein, which is designated Tau antigen, has an apparent molecular weight of 56,000 as determined by electrophoresis on acrylamide gels. The relationship among Tau antigens isolated from different lines of simian virus 40-transformed cells was examined by comparing the methionine-labeled tryptic peptides of these proteins by two dimensional fingerprinting on thin-layer cellulose plates. In this fashion, we initially determined that the Tau antigens isolated from three different lines of transformed mouse cells were very similar. Second, we found that Tau antigen isolated from a line of rat transformants was closely related, but not identical, to the mouse cell Tau antigens. Approximately 70% of their methionine peptides comigrated in two dimensions. Finally, we showed that Tau antigen isolated from a line of transformed human cells was only partially related to the mouse and rat proteins. About 40% of the methionine peptides of the human protein were also contained in the Tau antigens from the other two species. These results strongly indicate that the Tau antigens isolated from these various simian virus 40 transformed cell lines contain common amino acid sequences. PMID- 6247504 TI - Adenovirus regulation of simian virus 40 macromolecular synthesis. AB - At low multiplicities of infection (1 to 5 PFU/cell), human adenoviruses grew inefficiently in monkey kidney cells as the result of a late transcriptional and/or translational defect. Through an unknown mechanism, coinfection with simian virus 40 (SV40) could overcome this block. Coincident with the onset of adenovirus DNA replication in coinfected monkey cells, however, there was a marked inhibition of SV40 DNA replication. Since this inhibition in SV40 DNA synthesis occurred in the presence of normal SV40 transcription and protein synthesis, we suggest that adenovirus competes with SV40 for molecules specifically required for DNA synthesis (e.g., SV40 T-antigen). At high multiplicities of adenovirus infection (50 PFU/cell), adenoviruses could grow efficiently in monkey kidney cells. In cells coinfected under these conditions, SV40 transcription was generally inhibited, as shown by a decrease in nuclear and cytoplasmic SV40 mRNA. PMID- 6247505 TI - Coronavirus multiplication strategy. I. Identification and characterization of virus-specified RNA. AB - We examined the synthesis of intracellular RNA in primary chicken embryo kidney cells infected with the avian coronavirus infectious bronchitis virus. Infected cells were labeled with (32)P(i) in the presence of actinomycin D for the duration of the viral multiplication cycle, and nucleic acids were extracted, denatured, and analyzed on agarose slab gels. Six major RNA species were found. None of these RNAs was found in extracts of mock-infected cells. All six of the virus-specified RNAs (designated species A through F) were single stranded, and RNA species F had the same electrophoretic mobility as purified viral genome RNA. The molecular weights of the five subgenomic RNAs were estimated to be 0.8 x 10(6), 0.9 x 10(6), 1.3 x 10(6), 1.5 x 10(6), and 2.6 x 10(6) for species A through E, respectively. All of the RNAs were polyadenylated and are therefore likely to be viral mRNA's. The RNAs were synthesized in approximately constant proportions throughout the viral multiplication cycle. Intracellular RNA species A, B, C, D, and F and the purified viral genome were analyzed by RNase T(1) fingerprinting. The results confirmed the identification of RNA species F as the intracellular genome and the derivation of the four smaller RNAs from the genome. Fingerprinting also showed that the intracellular RNAs constitute a nested set such that the nucleotide sequence of each RNA is contained within all larger RNAs and each larger RNA contains an additional sequence congruent with its greater size. Finally, the possible modes of transcription and translation of the infectious bronchitis virus RNAs are discussed. PMID- 6247506 TI - Transcription of reconstituted simian virus 40 nucleoprotein complexes. AB - The regulatory effects of host cellular histones on the transcription of simian virus 40 (SV40) DNA were investigated by using reconstituted and native SV40 nucleoprotein complexes (NPCs). Reconstituted NPCs were prepared from SV40 DNA and the combination fraction of five histones, H1, H2A, H2B, H3, and H4, isolated from the nuclei of permissive (CV-1) or nonpermissive (BALB/c 3T3, rat liver, and calf thymus) cells. Native NPCs were prepared by alkali disruption of purified SV40 virions. Nuclease digestion of these NPCs gave regular patterns of bands similar to those of SV40 NPCs from SV40-infected CV-1 cells, suggesting the presence of a nucleosomal structure. Transcription of NPCs was analyzed in vitro by using Escherichia coli DNA-dependent RNA polymerase. Both histone H1 and the fraction consisting of all five histones inhibited transcription of SV40 DNA by about 90 to 95%. The fraction consisting of four histones lacking H1 reduced the transcription by 30 to 35%, to a level similar to that of transcription with native NPCs. Transcription was inhibited regardless of whether the origin of histones was permissive or nonpermissive cells. Gel electrophoretic patterns of RNA products transcribed from SV40 DNA and reconstituted and native NPCs showed several identical peaks between 13S and 28S. The patterns were identical whether NPCs reconstituted with H1 alone, all five histones, or four histones lacking H1 were used. PMID- 6247507 TI - Biochemical transformation by temperature-sensitive mutants of herpes simplex virus type 1. AB - Biochemical transformation assays of herpes simplex virus type 1 temperature sensitive (ts) mutants distinguished three groups of mutants with regard to their thymidine kinase (TK) transforming ability: those incapable of transferring the TK gene at either the permissive or restrictive temperatures (group I); those resembling the wild-type virus, and therefore able to transform at both the permissive and nonpermissive temperatures (group II); and those that failed to transform or exhibited very low transformation frequencies at the permissive temperature but were able to transform at the nonpermissive temperature (group III). Two mutants in group II exhibited greatly enhanced transformation efficiency at the permissive temperature. The ts lesions in the majority of the mutants tested map between 0.30 and 0.60 units on the viral genome. Mutants with TK-positive (TK+), but DNA-negative, phenotypes at the nonpermissive temperature produced no TK+ transformants at the permissive temperature and only unstable transformants at the nonpermissive temperature. This suggests that a function which is required for viral DNA synthesis is also required to obtain stable expression or to transfer the TK+ gene or both when transfer is mediated by the entire viral genome. PMID- 6247509 TI - Avian reticuloendotheliosis virus: characterization of the high-molecular-weight viral RNA in transforming and helper virus populations. AB - Reticuloendotheliosis virus strain T (REV-T) is a type C retrovirus known to transform avian fibroblasts, spleen cells, and bone marrow cells and to produce virulent reticuloendotheliosis in young chicks. Analysis of REV-T high-molecular weight RNA by electrophoresis in denaturing gels and by electron microscopy revealed the presence of at least two classes of molecules. One class appeared in CH3HgOH gels to have a monomer length of 9.3 kilobases (kb); in electron microscopic spreads under mildly denaturing conditions, it existed as a typical retrovirus dimer, having a monomer length of 8.8 +/- 0.7 kb. The second class also existed as a dimer, with a monomer length of 5.7 kb in CH3HgOH gels. Hybridization with REVA-A 32P-labeled complementary DNA revealed a third size class of molecules (4.7 kb), which were not resolvable from the 5.7-kb class in electron microscope spreads and which comigrated with chicken 28S rRNA in denaturing gels. Only the 9.3-kb class was found in the reportedly nontransforming virus produced after infection of canine thymus cell line with REV-T. Thus, REV-T appears to be similar to the murine and feline sarcoma viruses and the avian acute leukemia viruses in that it consists of a nontransforming helper virus genome and a defective genome responsible for oncogenicity. Our previous results demonstrated the presence in REV-T and in uninfected chicken cellular DNA of some nucleotide sequences not found in virus produced by the canine line (S. Simek and N. Rice, J. Virol. 33:320--329, 1980). In this report we show by hybridization with highly specific 32P-labeled complementary DNAs that REV-T-specific sequences exist within the 5.7-kb genome. Since 32P-labeled complementary DNA synthesized from the canine-derived virus genome hybridized with all three classes of RNAs, we conclude that the 5.7-kb genome is a recombinant between some sequences found in the putative helper and some sequences specific to REV-T. As with the other oncogenic viruses mentioned above, these specific sequences appear to be derived from host DNA. PMID- 6247508 TI - Recombination and linkage between structural and regulatory genes of herpes simplex virus type 1: study of the functional organization of the genome. AB - Phenotypic and genetic properties of 12 markers in structural and regulatory functions of herpes simplex virus type 1 were characterized, and their recombination and segregation behavior was investigated and interpreted with reference to available information on their physical locations. The markers were: (i) ts markers in a structural glycoprotein (tsB5) and in alpha (immediate early; tsLB2, tsc75) or beta (early, delayed early; tsB1) functions with regulatory effects; together with (ii) plaque morphology (syn), phosphonoacetate resistance (Pr), and thymidine kinase (TK) phenotypes; and (iii) electrophoretically distinct variants of glycosylated (glycoprotein C, gpC; ICP10) and non glycosylated [VP(13-14), VP23] structural and nonstructural [ICP(47-48)] polypeptides. Mean two-factor recombination frequencies ranged from 2% (for noncomplementing mutants tsLB2 and tsc75) to 35 to 40% (for unlinked markers) and were influenced by the relative contributions of parental viruses to the mixed infection. Even with control of this variable, standard deviations of mean measures of recombination frequency ranged from a minimum of 14% (with n greater than or equal to 10) to 65% (with n = 3) of mean values; no recombination frequencies higher than 55% were observed. Differences in mean two-factor recombination frequencies between a small number of loosely linked markers were, therefore, not reliable measures of real differences in linkage. Measurements of the segregation of unselected markers among recombinant progeny were, therefore, used as measures of linkage. These experiments (i) established a linkage group for markers in the long unique region of the genome additional to, but consistent with, existing physical data, i.e., TK-syn-tsB5-(tsB1.Pr)-[gpC.VP(13-14)]; (II) identified markers, e.g., ICP(47-48), linked to regulatory mutations (tsLB2, tsc75) in redundant DNA sequences; and (iii) used the segregation of these regulatory mutations and linked markers among unselected progeny to demonstrate the linkage groups: Pr-syn-TK-tsc75-ICP(47-48), [VP(13-14).gpC]-Pr-syn-TK, and TK tsc75-[VP(13-14).gpC]. These results were most simply explained if bi- or intermolecular recombination occurred between circular molecules or molecules catenated "head-to-tail" and were incompatible with intermolecular recombination as the mechanism of isomerization of herpes simplex virus DNA. PMID- 6247510 TI - Electron microscopy of vesicular stomatitis virus replicative ribonucleoproteins. AB - The objective of this investigation was to examine by electron microscopy the replicative ribonucleoprotein (RNP) structures synthesized in vesicular stomatitis virus-infected HeLa cells. Pulse-labeled in vivo products of vesicular stomatitis virus replication and transcription can be separated by centrifugation in Renografin gradients. Transcription complexes are dissociated, allowing nascent messenger RNPs to remain at the top of the gradient, whereas RNPs biochemically consistent with replication complexes sediment to the middle of the gradient. Examination of these structures by electron microscopy revealed that all exist as coiled or helical RNPs having dimensions of approximately 20 by 700 nm. These structures can be further subdivided into three major morphological classes: (i) linear forms (20 by 769 +/- 158 nm), which have both ends free; (ii) circular forms (20 by 679 +/- 95 nm), which appear to have both ends joined; and (iii) complex forms, which include those structures which are branched replicative complexes as well as those which are random. To distinguish random complexes and possible transcriptive complex contaminants from replicative complexes, it was necessary to uncoil the RNP structures with EDTA so that length measurements could be made relating the nascent strand length to its position on the template. After EDTA treatment, the linear RNPs uncoiled (10 by 4,035 +/- 3,802 nm), and the circular morphology virtually disappeared. However, a new form appeared which was one-half the length and double the width (20 by 2,103 +/- 306 nm) of full-length RNPs and contained a loop at one end and two free ends at the other (alpha-form RNP). The distribution and length analysis of these structures, plus and minus EDTA, suggest that the alpha-form RNPs arise by EDTA-induced uncoiling of circular forms held together at the ends. Close scrutiny of uncoiled complex RNPs revealed no single-strand RNP templates with single-strand nascents. However, several complexes were observed which appeared to contain alpha-form templates with single-strand nascent RNPs. Length measurements suggest these complexes are neither random nor transcriptive, but are replicative. These experiments suggest that replication may, in part, occur on circular coiled RNP templates. PMID- 6247511 TI - Transformation of rat cells by fusion-infection with Rous sarcoma virus. AB - The transformation of a rat cell line, 3Y1, by nonmammalian tropic strains of avian sarcoma virus was tested using cell-virus fusion mediated by Sendai virus or polyethylene glycol. Furthermore, the establishment of several transformed 3Y1 cell clones induced by the Schmidt-Ruppin strain of Rous sarcoma virus (RSV), its derivative mutants, and the Bryan high-titer strain of RSV is reported. The presence and expression of the viral genomes in these cells were examined, and all transformed cell clones tested were found to contain rescuable RSV genomes when they had been fused with normal chicken embryo fibroblast cells or those preinfected with Rous-associated virus type 1. However, the gag gene product, pr76, was barely detectable in wild-type RSV-transformed cells, whereas it was produced in considerable amounts in cells transformed by env-deleted mutants, the Bryan high-titer strain of RSV and NY8 derived from the Schmidt-Ruppin strain of RSV. PMID- 6247512 TI - Is cytoskeleton involved in vesicular stomatitis virus reproduction? AB - CER cells infected with vesicular stomatitis virus showed a morphology similar to that observed after cytochalasin B treatment. Temperature-sensitive mutants affected in envelope protein maturation did not induce those morphological changes at a nonpermissive temperature. In addition, the cytoskeleton was not implicated in vesicular stomatitis virus reproduction. PMID- 6247513 TI - Cytoplasmic T antigens of mouse and human cells transformed by a simian virus 40 tsA mutant. AB - Simian virus 40 T antigens accumulate in the cytoplasm of simian virus 40 tsA207 transformants of primary mouse kidney or human retinoblastoma cells grown at 40 degrees C in 10% serum. PMID- 6247514 TI - Proposal for a uniform nomenclature for defective interfering viruses of vesicular stomatitis virus. AB - Defective interfering particles of vesicular stomatitis virus have been named according to their parental derivation and to their genomic length and physical properties. This suggested uniform nomenclature can be adapted for other virus systems. PMID- 6247515 TI - Necrosis of Wilms tumors. AB - Gray scale ultrasonography, arteriography and excretory urography were done in 17 children with Wilms tumor. The results of these studies were correlated with the pathological specimen. At the time of operation 71 per cent of the tumors were necrotic. Ultrasonography predicted correctly the internal consistency of Wilms tumors in 94 per cent of the cases, while arteriography was 64 per cent and excretory urography was 41 per cent accurate. This information regarding neoplastic degeneration added to the completeness of the radiographic examination and forewarned the surgeon of a potentially difficult resection. PMID- 6247516 TI - Polypoid renal pelvic lesions in children. AB - A case is presented of gross hematuria and a large polypoid renal pelvic mass in a 15-month-old boy. Operation revealed a Wilms tumor with limited parenchymal involvement and rupture into the collecting system. This rare presentation of nephroblastoma and its differentiation from other rare benign and malignant renal pelvic lesions occurring in the pediatric patient are discussed. The advantages and disadvantages of radical and conservative surgical approaches to these rare lesions are reviewed. Preoperative cystoscopy and retrograde pyelography are mandatory in all patients with renal tumors presenting with gross hematuria, regardless of age. Radical nephrectomy with total ureterectomy is recommended for Wilms tumor with extension into the collecting system. PMID- 6247517 TI - Malignant fibrous histiocytoma of the kidney. AB - We report on a 33-year-old woman with malignant fibrous histiocytoma of the kidney. This malignant mesenchymal tumor is indistinguishable clinically and radiologically from a renal cell carcinoma. In our patient the tumor recurred locally following nephrectomy and metastasized to the lung. Post-nephrectomy radiation and chemotherapy may not alter the poor prognosis. PMID- 6247518 TI - Comparison of chlorine dioxide and chlorine in wastewater disinfection. PMID- 6247519 TI - Swine flu sequelae. PMID- 6247520 TI - Guillain-Barre syndrome in recipients of A/New Jersey influenza vaccine. AB - In late 1976, when 32% of the eligible population of Ohio received the A/New Jersey influenza (swine flu) vaccine, systematic contact of neurologists was used to evaluate the possible association of Guillain-Barre syndrome (GBS) with receipt of the vaccine. The overall rate of GBS was significantly higher among vaccine recipients (13.3/10(6)) than in nonrecipients (2.6/10(6)). Peak time of onset was two to three weeks after receiving the vaccine, and cases among vaccinees were less likely to have a history of antecedent infection than were cases in unvaccinated persons. Even when the effect of one highly associated vaccine lot was removed, an elevated risk of GBS remained in vaccinees regardless of manufacturer or vaccine type (bivalent or monovalent). Systematic surveillance is needed for rare serious reactions from all vaccines. PMID- 6247521 TI - Long-term survival in small cell carcinoma of the lung. AB - From June 1973 to August 1977, three hundred thirty-seven patients with small cell carcinoma of the lung were included in randomized therapeutic trials. By February 1979, fifty-one patients (15%) had survived for 18 months, including 29 (9%) in clinical complete remission. Of the latter patients, readmitted for restaging, including bone marrow examination, peritoneoscopy, and bronchomediastinoscopy, residual tumor was found in four. Treatment was discontinued in the remaining patients; six subsequently had relapses, while three patients died, free of disease, of other causes. Sixteen patients are still alive and free of disease more than 19 to 50 months after the primary diagnosis; seven were treated with combination chemotherapy alone, including four who initially had distant metastatic disease. The remaining nine patients had regional disease and were treated with both chemotherapy and radiotherapy, including prophylactic brain irradiation in four patients. Long-term survival can be achieved in a small number of patients in all stages of small cell carcinoma with intensive combination chemotherapy. PMID- 6247522 TI - [Paralysis of the peripheral nerve following radiotherapy for mammary carcinoma (author's transl)]. PMID- 6247523 TI - Double transformation of Indian muntjac cells by avian and murine sarcoma viruses. AB - Avian sarcoma virus-transformed Indian muntjac cells, SR-Mm-1, formed foci by murine sarcoma-xenotropic murine leukemia virus complex [MSV(X-MuLV)] superinfection. The response of SR-Mm-1 and parental normal Indian muntjac Mm-2K cells to MSV(X-MuLV) infection was compared. Focus formation by MSV(X-MuLV) followed two-hit kinetics in Mm-2K, but one-hit kinetics in SR-Mm-1 cells. MSV(X MuLV)-infected SR-Mm-1 cells formed larger colonies than uninfected SR-Mm-1 cells in soft agar, while no colony was formed in the MSV(X-MuLV)-infected Mm-2K cells. After infection with MSV(X-MuLV), cell clones doubly transformed by avian and murine sarcoma viruses could be established in SR-Mm-1 cells, whereas no cell clone could be established in Mm-2K cells. The doubly transformed cells were more round and refractile than SR-Mm-1 cells. No specific chromosomal change could be detected among Mm-2K, SR-Mm-1, and the doubly transformed cells. By two dimensional polyacrylamide gel electrophoresis of cellular proteins, several changes were seen between Mm-2K and SR-Mm-1 cells. In MSV(X-MuLV)-infected Mm-2K and SR-Mm-1 cells, several similar changes in polypeptide patterns were seen as compared with uninfected cells. These results indicate that Mm-2K cells were doubly transformed by avian and murine sarcoma viruses, and MSV transformation in SR-Mm-1 cells was different from that in Mm-2K cells. PMID- 6247524 TI - [Endotoxin in severe liver diseases (author's transl)]. PMID- 6247525 TI - [Cytotoxicity of peripheral lymphocytes from patients with hepatoma on human hepatoma cell line. IV. Electron microscopic studies on the in vitro interaction between human lymphocytes and human cultured hepatoma cells (author's transl)]. PMID- 6247526 TI - [Clinical experience with an oral angiotensin I-converting enzyme inhibitor in hypertensive patients: effects on blood pressure and the renin-aldosterone system by a single dose (author's transl)]. PMID- 6247527 TI - [Studies on ammonia metabolism in hypoxia. III. Enzymatic analysis on renal ammoniagenesis in hypoxia (author's transl)]. PMID- 6247528 TI - [Effects of angiotensin converting enzyme inhibitor SQ 14,225 on the blood pressure, renin-angiotensin-aldosterone system and renal function in patients with malignant hypertension (author's transl)]. PMID- 6247529 TI - [Experimental nephritis induced by Cox. B4 virus in mice (author's transl)]. PMID- 6247530 TI - [Complications and aftercare of colostomy]. PMID- 6247531 TI - [Conference: after care of patients with colostomy]. PMID- 6247532 TI - Pathology of non-effusive type feline infectious peritonitis and experimental transmission. PMID- 6247533 TI - A case of canine respiratory adenovirus infection associated with distemper. PMID- 6247534 TI - Herpesvirus type 2 infection of the genital tract. PMID- 6247535 TI - [Angiotensin converting enzyme (ACE) a bloodtest for diagnosis of sarcoidosis (author's transl)]. AB - Serum angiotensin-converting enzyme (ACE) was studied in 50 patients with sarcoidosis (39 active, 11 inactive) as well as in 50 control patients (34 with chronic nonspecific lung disease, 9 with Hodgkin and 7 with rheumatoid arthritis). There was a significant difference of ACE activity between sarcoidosis patients (28.6 +/- 11.4) and controls (14.8 +/- 4), and also between active (32.8 +/- 11) and the inactive (21.9 +/- 5.1) sarcoidosis (p less than 0.001). Coricosteroid treatment seems to lower ACE activity in patients with sarcoidosis without offering a clue for clinical improvement. Increased ACE activity in other granulomatous disorders is being discussed. ACE activity thus proves to be a valuable test especially in differentiating active from inactive sarcoidosis. PMID- 6247536 TI - [Value of angiotensin I-converting enzyme in the diagnosis of sarcoidosis (author's transl)]. AB - Serum ACE activity measured fluorimetrically was found to be 2.95 +/- (SD) 1.76 mu mol/ml x h in 31 untreated patients with sarcoidosis. It was significantly elevated (p less than 0.001) in comparison to 38 healthy controls 0.97 +/- (SD) 0.30 mu mol/ml x h), 81 subjects with miscellaneous lung diseases, 20 corticosteroid treated patients with sarcoidosis and 15 subjects with resolved sarcoidosis. Resolution of sarcoidosis spontaneously or induced by corticosteroids was accompanied in all 17 cases by a decrease of serum ACE activity, in most cases, to normal values. On the other hand 7 out of 9 untreated patients with a chronic course of sarcoidosis did not show a comparable change of ACE. Our results reveal a close relationship between the activity of the disease and the level of ACE in the serum. The determination of the serum activity of ACE and its variations with time is quite useful in the diagnosis and follow-up of sarcoidosis and contributes to a further restriction of necessary operative procedures in the diagnosis of sarcoidosis. PMID- 6247537 TI - [Heterotopic ulcerogenic insuloma]. PMID- 6247538 TI - [Clinical aspects of VZ viral hepatitis and the aggravating effect of herpes zoster on the course of infectious and serum viral hepatitis]. PMID- 6247539 TI - [Nurse and patient: how their relationships develop]. PMID- 6247540 TI - [Rooming-in]. PMID- 6247541 TI - [Spoof: a human wreck]. PMID- 6247542 TI - [Survey of male and female nurse anesthetists]. PMID- 6247543 TI - [Observations on a preventive aspect of sudden death at home]. PMID- 6247544 TI - [Sudden and unexplained infant death syndrome]. PMID- 6247545 TI - [Care for the dying, accompanying the dying. Bibliography]. PMID- 6247546 TI - [Our role in the promotion of primary health care]. PMID- 6247547 TI - [The rights of the patient and its hospital organization in the light of the European Council]. PMID- 6247548 TI - [The Swiss Nurses' Association-Geneva proposes modifications in legislation concerning the practice of medical and auxiliary professions to the Council of State]. PMID- 6247549 TI - [Flash on the Swiss Hospital Institute, Aarau]. PMID- 6247550 TI - [The serratias]. PMID- 6247551 TI - [Patient-oriented care in theory and at the bedside]. PMID- 6247552 TI - [Equal and different: a backward look at the week of the Handicapped Child in Basel: an unforgettable experience]. PMID- 6247553 TI - [Practice shock?--Then practice guidance! Is supervision a possibility for the assimilation of reality shock? Report on project "Practice Guidance" of the professional Nursing School in Zurich]. PMID- 6247554 TI - [Observations of a western psychiatrist on medical care for Cambodians]. PMID- 6247555 TI - [Nursing students. Diary notes from an everyday student day]. PMID- 6247556 TI - [Hospital housekeeping employee(s): a new occupation in the hospital and nursing home field]. PMID- 6247557 TI - [Living together at the bedside and elsewhere]. PMID- 6247558 TI - [Rights of the hospital patient]. PMID- 6247559 TI - [Orientation of new colleagues]. PMID- 6247560 TI - ["Nursing Policies 1980"]. PMID- 6247561 TI - [Red Cross service - ready in case of war and in disaster situations]. PMID- 6247562 TI - [Search and you shall find! Nicole Exchaquet retires]. PMID- 6247563 TI - [Thank you to Nicole France Exchaquet]. PMID- 6247564 TI - [Primary health services: concrete examples in Switzerland and in the world]. PMID- 6247565 TI - [Congress on the education of infant educators; Zurich, 26 and 27 November 1979]. PMID- 6247566 TI - [Sleep: physiology, disorders, treatment]. PMID- 6247567 TI - [Pigmented skin tumors]. PMID- 6247568 TI - Retinoic acid-binding protein in a human cell (MCF-7) from breast carcinoma. AB - A specific retinoic acid-binding protein was demonstrated by sucrose density gradient centrifugation and saturation binding analysis in MCF-7 human breast cancer cells. In contrast, retinol-binding protein could not be detected in this cell line. By Scatchard analysis, this retinoic acid-binding protein was found to have a dissociation constant (Kd) of 154 nM and to bind a maximum of 14 pmoles of [3H] retinoic acid per milligram of cytoplasmic protein. Experiments with intact attached cells revealed the Kd to be 125 nM, which is very close to the value obtained for cytoplasmic extract. The binding of [3H] retinoic acid was abolished by unlabeled retinoic acid. Retinal and alpha-retinoic acid competed for binding sites but were less potent than unlabeled retinoic acid. Retinol, retinyl acetate, and the analog Ro 10-9359 showed little of no competition for the retinoic acid-binding site. A specific retinoic acid-binding protein was also demonstrated by gel electrophoresis. The presence of retinoic acid binding protein in MCF-7 cells suggests that the biologic effects of retinoic acid may be mediated by this specific protein. PMID- 6247569 TI - Study of thickened nerves in a leprosy endemic region. Part II--Ultrastructural and tease fibre study. AB - Ten out of sixteen cases of thickened nerves labelled as having idiopathic neuropathy showed hypertrophic changes, when their peripheral nerves were observed under light microscopy. Electron microscopy of seven nerves revealed more details. The reactions in various parameters of nerves were recorded. The significant observation was of one case harbouring Lepra bacilli as seen under electron microscope and having other changes similar to changes seen in early cases of leprosy. Two cases were also thought to have leprosy on the basis of the ultrastructural observation on their nerves. These could have been missed otherwise. PMID- 6247570 TI - Medical applications and use of marijuana--a study by the Tennessee Department of Public Health. PMID- 6247571 TI - Placental origin of the suppression of 3 beta-hydroxysteroid dehydrogenase in the fetal zone cells of human fetal adrenals. PMID- 6247572 TI - Subcellular metabolic pools in the rat adrenal gland. In vivo effect of acute stimulation with ACTH on steroid biosynthesis. PMID- 6247573 TI - Time-course of the effect of treatment with a potent LHRH agonist on testicular steroidogenesis and gonadotropin receptor levels in the adult rat. PMID- 6247574 TI - Plasma and urinary androgens and oestrogens in a pubertal boy with 3 beta hydroxysteroid dehydrogenase deficiency. PMID- 6247575 TI - Alternative pathways in human corticosteroid biosynthesis. PMID- 6247576 TI - Effect of catechol estrogens and estriol on the induction of uterine peroxidase. PMID- 6247577 TI - Inhibition of ACTH responsiveness of adrenocortical and fat cells adenylate cyclase by 4-methyl-4-aza-5 alpha-cholestane. PMID- 6247578 TI - Hormonal regulation of activities of 4-ene-5 alpha-reductase and 17 beta-ol dehydrogenase in adult androgen-sterilized rat ovaries. PMID- 6247579 TI - Clinicomorphologic markers for predicting behavior and guiding therapy for brain tumors. AB - More specific therapy can be achieved for brain tumors by identifying morphologic markers like primitive neuroectodermal tumor cells that tend to be radioresponsive and spread diffusely through the cerebrospinal fluid (CSF). Utilizing clinical manifestations to suspect and then localize the brain tumor, morphologic markers, that can be appreciated with computerized tomography and cerebral angiography as well as at operation, provide a basis for more aggressive extirpation and the usefulness of radiation and chemotherapy. Metastatic neoplasms possess such markers as tumor hemorrhage and meningeal involvement suggesting specific extraneural sources. In almost half of these patients, cytologic examination of the CSF should help to identify the malignant cells. Although most gliomas do not metastasize either within or outside the central nervous system, the occurrence of primitive neuroectodermal tumor cells (undifferentiated malignant small cells) in about 20% of all glioblastomas implies spread throughout the CSF and some radioresponsiveness. With thorough clinicomorphologic evaluations of all patients with brain tumors in concert with liberal clinical consultations, the aggressive, newer therapeutic modalities can be used more effectively. PMID- 6247581 TI - Markov analysis of viral DNA/RNA sequences. PMID- 6247580 TI - Studies of tumor implants in immunologically privileged sites. AB - Wilms' tumor, renal cell carcinoma, and neuroblastoma in animals were transplanted from donors to recipients with strong histocompatibility differences. No strong evidence of the privileged site theory was found in this study and no obvious evidence of an immunosuppressive effect of testosterone was found. The most important factor noted in these studies was that the take of tumor transplant seems to be related more to the type of tumor itself. Further studies of transplant results of such different types of tumors are warranted and are being conducted. An interaction between the hormonal supportive concept and the privileged site seems tenable. PMID- 6247582 TI - Pseudolymphoma of the lung: a rare cause of a solitary nodule. A case report and review of the literature. AB - Pulmonary pseudolymphoma is a rare lesion; only 30 cases have been previously reported. It presents as a solitary nodule which clinically and roentgenographically can resemble bronchogenic carcinoma. A further case is reported in which preoperative needle aspiration cytology played a role in diagnosis. Although the lesion was originally believed to be benign, a review of the literature has revealed the apparent subsequent development of lymphoma in four cases. The significance of this is discussed, and the need for prolonged follow-up is emphasized, since the prognosis of untreated pseudolymphoma is unknown. PMID- 6247583 TI - Radiographic changes in chrysotile mine and mill ex-workers in Corsica. A survey 14 years after cessation of exposure. PMID- 6247584 TI - Visceral leishmaniasis (kala-azar) as a cause of fever of unknown origin. AB - A patient with a rare cause of fever of unknown origin, visceral leishmaniasis (kala-azar), is reported. The diagnosis was made by exploratory laparotomy and splenectomy after diagnostic studies had failed to reveal the cause of the fever. The patient was cured with a 6-day course of therapy with Pentostam (sodium antimony gluconate). Visceral leishmaniasis should be considered in the differential diagnosis of patients with obscure fever who have traveled in endemic areas. PMID- 6247585 TI - Reconstruction of the congenitally anomalous hand. PMID- 6247586 TI - A revised role for cyclic AMP in prostaglandin-induced bone resorption. AB - The effect of cyclic AMP on bone resorption produced by prostaglandin E1 (PGE1) and E2 (PGE2) was studied using 6--7 day-old murine calvarial bones cultured in a chemically defined medium for 48 h. Dibutyryl cyclic AMP inhibited in a dose related way the prostaglandin-induced mobilization of 45Ca from prelabelled bones. The phosphodiesterase inhibitors, theophylline and 3-isobutyl methylxanthine, also reduced the release of 45Ca induced by the prostaglandins. It was also found that the doses of the later phosphodiesterase inhibitor needed to inhibit prostaglandin-stimulated mineral mobilization were lower than those needed to reduce unstimulated resorption. The mechanism behind the inhibitory effect of cAMP on prostaglandin-induced bone resorption is unknown, but might be related to the capacity of cAMP to inhibit prostaglandin-stimulated release of lysosomal enzymes, which was also demonstrated in this study. PMID- 6247587 TI - Nuclear war against herpesviruses. PMID- 6247588 TI - [New enzymatic and endocrinological aspects in two cases of Werner's syndrome (author's transl)]. AB - Results of endocrinological studies and of the investigation of intraerythrocytic glycolytic pathway carried out in two patients with Werner's syndrome are presented. An increase of glyceraldehyde 3-phosphate and 3-phospho-glycerokinase has been observed, but the significance of these original findings is still unknown. An hyperinsulinism after oral glucose overload has been demonstrated too. This finding, which has been reported by other authors, probably reflects a peripheral resistance to insulin action. Other endocrinological abnormalities were a decrease in the T3:T4 quotient and a slight delay in the FSH-LH peak to LH RH. PMID- 6247589 TI - [Turner's phenotype in a male with deficit of ACTH and gonadotropins (author's transl)]. AB - A case of male Turner's syndrome in a 23-year-old patient is reported. Clinical features included total eunuchoidism, shield-like chest, cubitus valgus, lymphedema in the extremities (hands and feet) and a shortened fourth metacarpal. Hormonal studies revealed very low levels of gonadotropins, cortisol, testosterone and HGH, and normal values for PRL and TSH. Gonadotropin levels did not change after the administration of 100 micrograms LH-RH and 500 micrograms LH RH every 8 hours during 5 days. Testosterone levels increased when HCG was given. Deficit of ACTH release was demonstrated after the administration of metopyrone, ACTH and 0.1 UI insulin per kilogram of body weight to induce hypoglycemia. Hypoglycemia with insulin and arginine did not determine an increase of GH levels, instead of previous estrogen therapy. These results reveal a hypophyseal hormonal defect in relation to ACTH, LH, FSH and GH release. Hormone abnormalities found in the present case have not been previously described. PMID- 6247590 TI - Increasing number of beta-adrenergic receptors in intact, differentiating muscle cells. PMID- 6247591 TI - Studies on the iodination of LH-RH and the biological and immunological activities of the products. PMID- 6247592 TI - Deoxyribonuclease I binding masks the major tryptic cleavage sites on actin. PMID- 6247593 TI - Pharmacological profile of a model for central serotonin receptor activation. PMID- 6247594 TI - Location and characterization of opiate receptors regulating pituitary secretion. PMID- 6247595 TI - Beta-adrenergic receptor-linked adenylate cyclase in rat posterior pituitary. PMID- 6247596 TI - Electroacupuncture analgesia is mediated by stereospecific opiate receptors and is reversed by antagonists of type I receptors. PMID- 6247597 TI - [Binding and the effect of ACTH-3H depending on the state of the adrenal gland]. PMID- 6247598 TI - [Characteristics of the biological action of high-energy helium ions and protons]. PMID- 6247599 TI - [Mediastino-pulmonary sarcoidosis in Ivory Coast. Epidemiological and clinical significance of sixteen new cases observed in Abidjan (author's transl)]. AB - Sixteen cases of mediastion-pulmonary sarcoidosis are reported, half of them presenting extra-thoracic associated lesions. The clinical and epidemiological study of these cases, compared to the previously published ones, demonstrates that the clinical features are similar in Africans and Black Americans and that the disease in coming out in Africa South of the Sahara. PMID- 6247600 TI - [Gastro-duodenal perforating ulcers. Therapeutic trend in African patients (a study of 80 cases recorded in Abidjan) (author's transl)]. AB - 80 perforating ulcers recorded during 7 years (1970-1976) in Abidjan hospitals are reviewed. The therapeutic tactic is discussed according to the traditional and socio-economic living patterns of african patients: the authors propose a complete surgical treatment carried out either directly or after some delay but without discharging the patient who, in most cases, would no more report to the hospital. Suture may be an emergency treatment in patients with poor condition but it must be completed later during the same confinement. PMID- 6247601 TI - Transfers of esterified cholesterol and triglyceride between high density and very low density lipoproteins: in vitro studies of rabbits and humans. PMID- 6247602 TI - Hypolipidemic effects of high-carbohydrate, high-fiber diets. PMID- 6247603 TI - Effects of some clinically encountered drugs on steroid synthesis and degradation. PMID- 6247604 TI - Calcium antagonists and hormone release. I. Effects of verapamil on insulin release in normal subjects and patients with islet-cell tumor. AB - Intravenous infusion of verapamil, an organic antagonist of calcium transport into cells, produced a marked and significant inhibition of glucose-, glucagon- and sulfonylurea-induced increases in serum insulin in normal subjects. Also, blood glucose concentrations remained significantly higher after the secretagogue plus verapamil than after the secretagogue alone. Blood glucose concentrations increased regularly after verapamil + glucagon administration indicating that verapamil is not capable of inhibiting the hepatic glycogenolysis induced by glucagon. Two patients with islet-cell tumor, treated with verapamil for 5 days, experienced a decrease in the severity and frequency of hypoglycemic attacks while "autonomous" insulin release was inhibited. The present results clearly show that calcium antagonists are capable of inhibiting insulin response to appropriate stimuli in normal subjects. Therapeutic association of calcium antagonists and sulfonylureas should be used with caution in the light of the present findings. Calcium antagonists can be useful drugs in the treatment of hypoglycemia caused by islet-cell tumor. PMID- 6247605 TI - Fasting, but not glucagon administration, decreases anterior pituitary nuclear thyroid hormone receptors in rats. PMID- 6247606 TI - Purification and partial characterization of cardiac plasma membranes rich in beta-adrenoreceptors. AB - A procedure was developed to purify plasma membranes from cardiac tissue. Canine ventricular tissue was homogenized relatively gently in hypotonic buffer, extracted briefly with 0.15 M sodium perchlorate at 4 degrees C, and membranes were collected in an intermediate pellet by centrifugation at 27,500 X gmax. At this stage, most contractile proteins were removed (although Z-band structures were apparent), and the recoveries of Na+, K+-ATPase, beta-adrenoreceptors and 5' nucleotidase were 40--50%. Treatment of these particles with 0.5% dextran sulfate and continuous density gradient centrifugation resulted in the separation of membranes having 111 and 3.6 pmol/mg protein specific binding sites for [3H] ouabain and [3H] dihydroalprenolol, respectively. Electron micrographs showed medium-sized vesicles. 5'-Nucleotidase was also markedly purified but could be partially separated from the other plasma membrane markers in continuous sucrose gradients. Enzymes associated with mitochondria, lysosomes, and endoplasmic reticulum were efficiently removed. SDS-polyacrylamide gels showed six major and many minor bands. Adenylate cyclase remained responsive to hormones and Gpp(NH)p, but little purification was apparent. The membrane preparation has proved useful for studies of a nucleotide-binding protein associated with cyclase activation. PMID- 6247607 TI - Electron spin resonance and fluorescence observations on erythrocytes, erythrocyte membranes, 13762 MAT-A ascites adenocarcinoma cells, and their membranes, effects of membrane perturbations. AB - Membranes from erythrocytes or MAT-A 13762 tumor cells were labeled with the fatty acid spin probe I(5,10) or ANS and examined by spin resonance (ESR) or fluorescence polarization in the presence or absence of the perturbants EDTA, trypsin, glutaraldehyde, and dodecylsulfate. Extraction of cell membranes with hypotonic EDTA produced fragments in which the order parameters and fluorescence polarization values increased. Fluorescence polarization values using membranes labeled with diphenylhexatriene showed an apparent increase in membrane fluidity. A large portion of both I(5,10) and both fluorescence probes coextract with the peripheral membrane proteins in both membrane systems. Paramagnetic quenching of tryptophan fluorescence with I(5,10) and the spectral characteristics of ANS in these membranes indicated further that significant amounts of both probes bind either at or near the protein-lipid interface or directly to protein moieties. Trypsinization of cell membranes, which preferentially cleaves the large cytoskeletal proteins, fragmented the membranes and reduced the ESR order parameter. Glutaraldehyde immobilized I(5,10) in both types of membranes. These studies suggest that the association of cytoskeletal proteins with the membrane does not have any pronounced, consistent effect on biophysical properties of the bilayer. Attempts to apply these same probes to studies of the plasma membranes of intact cells were not successful because of the diffusion of the probes into the cells. These studies also point out some difficulties in using probe-group techniques to determine the nature of changes in bilayer structural parameters and emphasize the need for a better understanding of probe-group localization and behavior in such studies. PMID- 6247608 TI - Genetic instability in Drosophila melanogaster: evidence for regulation, excision and transposition at the white locus. AB - An unstable long tandem duplication which includes the white locus twice, marked with wsp in the left and w17g in the right locus, when kept in males has been found to produce red-eyed sons which have lost the long duplication and with it the wsp and w17g mutants. Such exceptions were produced also when w17g had been exchanged for wa. Stocks originating from these exceptions are unstable, producing: 1) zeste males, also unstable, 2) w- deletions, stable, 3) transpositions of the white locus to sites in other chromosomes. The instability is interpreted as the effect of an IS element, within or adjacent to the white locus, which is supposed to retain a duplication of the proximal zeste interacting part of this locus. According to the orientation of the IS element the duplicated part can be active or inactive, giving a zeste or red eye phenotype. The frequency of exceptional offspring after X-ray treatment of the red and zeste unstable stocks have been compared to stable stocks with corresponding genotypes. PMID- 6247609 TI - Effect of DNA sequences adjacent to the termini of Tn3 on sequential translocation. AB - Insertion of Tn3 generates a five base pair repeat of a nucleotide sequence indigenous to the recipient genome. Tn3 promoted deletions extend precisely from the Tn3 terminus and remove one of the 5 base pair repeats while not affecting the ability of Tn3 to subsequently undergo translocation. A direct repeat of a 10 bp sequence located in the Tn3 termini occurs internally within Tn3 and may affect the orientation of insertion. PMID- 6247610 TI - pdsA, a gene involved in the production of active phosphodiesterase during starvation of Dictyostelium discoideum amoebae. PMID- 6247611 TI - The boundaries and copy numbers of Ti plasmid T-DNA vary in crown gall tumors. AB - The Ti plasmid DNA maintained in octopine-type crown gall tumor lines is variable, but always includes at least part of the Ti plasmid that maps over the region of Hind III fragment 1 of pTiB6-806. The right-hand boundary of transferred DNA (T-DNA) varies considerably among the three independent tumor lines examined; the left boundary was not located definitively. The T-DNA of two sibling clones of the same tumor line, E1 and E9, appears identical. The copy number of T-DNA in E9 tumor DNA appears higher for the right end (about 30 copies) than for the left end (approximately 1 copy). PMID- 6247612 TI - Genetic evidence for absence of transposition functions from the internal part of Tn981 a relative of Tn9. AB - Inverse transposition of the DNA of pBR322 was found to be mediated by the small transposon Tn981 a relative of Tn9 flanked by direct repeats of IS1. Since the resulting structure IS1::pBR322::IS1 (Tn983) is transposed in a second step in the absence of Tn981, it is concluded that all the functions necessary for transposition of IS1 flanked transposons are coded for by IS1 itself or the E. coli chromosome, respectively. PMID- 6247613 TI - Organization of the nuclear ribosomal DNA of Chlamydomonas reinhardii. AB - Hybridization of cytoplasmic ribosomal RNA (rRNA) to restriction endonuclease digests of nuclear DNA of Chlamydomonas reinhardii reveals two BamHI ribosomal fragments of 2.95 and 2.35 x 10(6) d and two SalI ribosomal fragments of 3.8 and 1.5 x 10(6) d. The ribosomal DNA (rDNA) units 5.3 x 10(6) d in size, appear to be homogeneous since no hybridization of rDNA to other nuclear DNA fragments can be detected. The two BamHI and SalI ribosomal fragments have been cloned and a restriction map of the ribosomal unit has been established. The location of the 25S, 18S and 5.8S rRNA genes has been determined by hybridizing the rRNAs to digests of the ribosomal fragments and by observing RNA/DNA duplexes in the electron microscope. The data also indicate that the rDNA units are arranged in tandem arrays. The 5S rRNA genes are not closely located to the 25S and 18S rRNA genes since they are not contained within the nuclear rDNA unit. In addition no sequence homology is detectable between the nuclear and chloroplast rDNA units of C. reinhardii. PMID- 6247614 TI - Cloning of the immunity repressor determinant of bacteriophage P2 in the pBR322 plasmid. AB - Through in vitro recombination of DNA restriction fragments, we have constructed a plasmid, which expressed in vivo the immunity repressor gene (C) of bacteriophage P2. A bacterial strain carrying such a plasmid showed a high level of P2 specific immunity. It was lysogenized normally by an infecting P2, but the frequency of spontaneous phage production was reduced about 10(4) fold as compared to a normal P2 lysogen. Satellite phage P4, known to derepress P2 lysogens, was unable to derepress the plasmid-carrying lysogenic strain so to allow growth of coinfecting P2. Phage P4 multiplied on the plasmid-carrying, P2 lysogenic strain, but due to a prolonged latent period failed to form plaques on this strain. PMID- 6247615 TI - Transposition of IS1-lambdaBIO-IS1 from a bacteriophage lambda derivative carrying the IS1-cat-IS1 transposon (Tn9). AB - Tn9 is a transposable element in which a gene (cat) determining chloramphenicol resistance is flanked by directly repeated sequences that are homologous to the insertion sequence IS1. We show here that infection of Escherichia coli K12 (under Rec-Red-Int- conditions) with a lambda bio transducing phage carrying Tn9 results in the formation of lambda bio transductants as frequently as cat transductants as frequently as cat transductants (about 1 per 10(6) to 10(7) infected cells). Most of the lambda bio transductants do not carry cat, just as most of the cat transductants do not carry lambda bio. In spite of the absence of cat, the lambda bio prophage can transpose a second time, from the E. coli chromosome to different sites on an F'gal plasmid. Analysis of the structure of the transposed lambda bio element, by restriction nuclease digestion and by electron microscopy, demonstrates that the integrated lambda bio prophage is flanked by directly repeated IS1 elements. We conclude that there is no genetic information for the ability to transpose encoded in the non-repeated portion of Tn9, i.e. that the directly repeated IS1 elements alone are responsible for Tn9 transposition. PMID- 6247616 TI - Serine sensitivity of Escherichia coli K 12: partial characterization of a serine resistnat mutant that is extremely sensitive to 2-ketobutyrate. AB - E. coli wild type bacteria display sensitivity towards serine. A selection medium is described which allows selection of serine resistant mutants. One such mutant is described which presents pleiotropic alterations: it exhibits a thermosensitive growth pattern, alteration in the metabolism of the pppGpp and ppGpp nucleotides, cAMP intracellular level alteration, extreme sensitivity to 2 ketobutyric acid and a defect in the phosphotransferases permeation system. A conjecture explaining these apparently unrelated defects supposes that serine metabolism interferes via phosphoenol pyruvate with a cytoplasmic control of membrane activity (the mutant would be defective in the coupling between membrane and the protein responsible for its cytoplasmic control) and that 2-ketobutyrate is an effector of this activity. PMID- 6247617 TI - Regulation of cyclic AMP of the ilvB-encoded biosynthetic acetohydroxy acid synthase in Escherichia coli K-12. AB - The biosynthetic acetohydroxy acid synthase activities of E. coli K 12 are encoded by three genetic loci namely, ilvB (acetohydroxy acid synthase I), ilvG (acetohydroxy acid synthase II) and ilvHI (acetohydroxy acid synthase III). The previously reported involvement of cyclic AMP in the regulation of the biosynthetic acetohydroxy acid synthase isozymes in E. coli K-12 was found to be due to the effect of this nucleotide on the expression of ilvB. Cyclic AMP had no effect on acetohydroxy acid synthase activity in strains lacking wild-type ilvB activity but containing the remaining isozymes. Very little activity of acetohydroxy acid synthase coded for by ilvV was found when ppGpp and cyclic AMP were severely limited. Addition of cyclic AMP under these conditions increased ilvB expression 24-fold. The data suggest that in addition to multivalent repression and ppGpp, cyclic AMP plays a major role in the regulation of the ilvB biosynthetic operon. PMID- 6247618 TI - Unusual behaviour of SPO1 DNA with respect to restriction and modification enzymes recognizing the sequence 5'-G-G-C-C. AB - SPO1 DNA contains only 5 cleavage sites for restriction enzymes which recognize and cleave the sequence 5'-G-G-C-C (HaeIII or BsuR). Fragments of SPO1 DNA cloned in E. coli to substitute 5'-hydroxymethyluracil (HMU) by thymine (T) remain resistant to HaeIII indicating that this unexpectedly small number of cleavages by HaeIII is not correlated with the presence of HMU in the normal phage DNA. It was previously shown that SPO1 is neither subject to B. subtilis R restriction (Trautner et al., 1974) nor modification in vivo (Gunthert et al., 1975). We now show that SPO1 DNA can however be restricted and modified in vitro. PMID- 6247619 TI - Electron microscopic mapping and sequence analysis of the terminator for the early message of E. coli phage T7. AB - The terminator position of T7 early messenger RNA was determined by electron microscopic measurements. The end of the RNA was mapped at a position 18.9% from the left end of T7 DNA, and 145 +/- 25 nucleotides from the right end of the Hpa I fragment Q. The sequence of the Hpa I Q fragment was determined around this position, and a terminator-like structure was detected in position 193 to 169 from the right end of fragment Q. PMID- 6247620 TI - Construction of a physical map of a kanamycin (Km) transposon, Tn5, and a comparison to another Km transposon, Tn903. AB - A cleavage map of Tn5, a kanamycin (Km) transposon from plasmid JR67, was constructed from pMKI, a composite plasmid of ColE1 and Tn5, and compared to that of Tn903, a Km transposon from plasmid R6-5. The two transposons showed marked heterogeneity in both the structural gene for Km resistance and the inverted repeat regions as evidenced by their distinctly different restriction maps. This result suggests separate paths of evolution for the two Km transposons. PMID- 6247621 TI - Demarcation of tissue channels by ferrocyanide deposits: use of an alternative precipitant. PMID- 6247622 TI - Trypsin action on the growth of Sendai virus in tissue culture cells. V. An activating enzyme for Sendai virus in the chorioallantoic fluid of the embryonated chicken egg. AB - A trypsin-like protease which is responsible for activation of Sendai virus was found in the chorioallantoic fluid (CAF) of embryonated chicken eggs. Treatment of the inactive form of Sendai virus, grown in LLC-MK2 cells, with CAF enhanced both hemolytic activity and infectivity for the cells. Soybean trypsin inhibitor restrained the enhancing activity of CAF. These results indicate that CAF contains a trypsin-like protease which activates the inactive form of Sendai virus. The activation was strongly inhibited by phenylmethylsulfonylfluoride, ethylenediaminetetraacetate, antipain, and leupeptin but not by tosyllysylchloromethylketone, suggesting that the activating enzyme in CAF is a protease similar to but not identical with trypsin. The inactive form of the virion was produced in ovo when the seed virus was inoculated along with antipain or leupeptin. In deembryonated chicken eggs in which CAF was substituted for a culture medium, multiple cycle growth occurred, but not when soybean trypsin inhibitor was present. These observations indicate that some activating enzyme, possibly the same one as found in CAF, was secreted from the chorioallantoic membrane. PMID- 6247623 TI - IgM antibodies to Epstein-Barr virus-associated membrane antigen in sera of infectious mononucleosis patients. AB - By the indirect immunofluorescence technique, IgM antibodies to the cell surface of an Epstein-Barr virus (EBV) producer cell line, P3HR-1, were detected in sera from infectious mononucleosis (IM) patients but not in sera from patients with Burkitt lymphoma or nasopharyngeal carcinoma nor in sera from healthy adult donors having antibodies to EBV-specific viral capsid antigen (VCA). Titers of the IgM antibodies were higher in the earlier stages of IM, a pattern similar to that for IgM antibodies to VCA. The IgM antibodies to the cell surface were identified as being those against the EBV-specific membrane antigen (MA) by the following criteria: (1) The antibodies were reactive to MA-positive cell preparations but to MA-negative cell preparations. (2) Titers of the IgM antibodies were not significantly affected after absorption of sera with sheep red blood cells which could completely eliminate heterophil antibodies in the same sera. Detection of the IgM antibodies to MA may have a particular diagnostic value for providing evidence of a recent EBV infection. PMID- 6247624 TI - Transformation of mouse peritoneal macrophages and bone marrow cells by simian virus 40. AB - A fraction of cultured mouse peritoneal macrophages and bone marrow cells acquired the ability to divide after infection by simian virus 40 (SV40). Two types of transformed lines were obtained. Most transformants isolated 400-60 days after infection did not display macrophage specific properties such as ingestion of opsonized red blood cells, possession of Fc receptors and complement receptors, and acid phosphatase activity throughout the whole culture phase. Cells of the transformed lines isolated by trypsin selection 2--6 months after infection displayed these properties when the cell density became high and cell growth was arrested. In the cells of the latter type of transformed lines, SV40 T antigen was intensely demonstrated by immunofluorescence in the growing phase, but weakly or not at all in the stationary phase. It is suggested that the reversion to the phenotype of the progenitor (expression of macrophage specific functions) depends on the physiological state of the culture; however, it is uncertain whether the development of the macrophage functions is directly related to the SV40 T-antigen. PMID- 6247625 TI - Effect of UV-irradiated human cytomegalovirus infection on exogenous thymidine metabolism in human embryonic lung cells. Variation depending cells. PMID- 6247626 TI - Adenylate cyclase activity of Bordetella organisms. I. Its production in liquid medium. AB - Abundant adenylate cyclase activity was found in the phase I cultures not only of Bordetella pertussis but also fo B. parapertussis and B. bronchiseptica. The enzyme activity in the culture fluid increased rapidly and reached a peak during the logarithmic growth phase. B. parapertussis and B. bronchiseptica especially produced a high activity of the enzyme in the culture fluid during the logarithmic phase, but little or no activity was detected in the cells throughout the growth period. In the culture of B. pertussis, the intracellular activity was higher than that in the culture fluid. Phase III cultures of these species lacked both the extracellular and intracellular enzyme activities throughout their growth. In the culture of B. parapertussis, accumulation of cyclic AMP was parallel to that of adenylate cyclase activity through the growth periods, but in B. pertussis there was no parallelism from the stationary through the declining phases. The difference in production patterns of the enzyme activity among the species is discussed. PMID- 6247627 TI - Lithium as an immunologic adjuvant. AB - Lithium, an adenylate cyclase inhibitor, stimulates a variety of in vitro indices of immune function, including proliferation of lymphocytes in response to mitogens, rosette formation by T-cells and phagocytosis by macrophages. Lithium enhances these immunologic responses at concentrations comparable to those achieved in patients receiving lithium for treatment of manic-depressive disorders. Lithium may prove to have important therapeutic applications as an immune adjuvant, particularly in immune deficiency states associated with excessive C-AMP production. PMID- 6247628 TI - Molecular interactions in biomedicine: modulation of regulatory behavior by cross reactivity: relevance to analysis of receptor function. AB - The influence of cross reactivity on biomolecular regulation is not frequently incorporated into theoretical analysis and is often eliminated by experimental design. Nonetheless, cross reactive molecules produce effects on binding which may considerably modulate their behavior in quite diverse systems, i.e., drug tissue receptor, antigen-antibody, substrate-enzyme, protein-DNA and hormone tumor receptor interactions. In particular, certain effects vary at different concentrations suggesting a simple control mechanism. PMID- 6247629 TI - Nuclear inclusions. PMID- 6247630 TI - Unimpaired histone synthesis in human fibroblasts infected by human cytomegalovirus. AB - Serum-starved human foreskin fibroblasts were infected by human cytomegalovirus (Towne strain) that is thought to induce DNA replication in host cells during lytic infection. At various times postinfection, the cultures were pulse labeled with either 3H-thymidine or 14C-thymidine and 3H-lysine to examine DNA synthesis and histone synthesis, respectively. Isopycnic centrifugation of labeled DNA in CsCl revealed that precursor incorporation into host-cell DNA was enhanced over the control around 24 h postinfection and decreased after onset of viral DNA synthesis which reached a peak around 72 h postinfection. For analysis of histones 3H-lysine-labeled proteins of lysates of unfractionated cells and of chromatin preparations were subjected to polyacrylamide gel electrophoresis in presence of sodium dodecyl sulfate and subsequent fluorography. Comparison of the fluorograms from the various pulses postinfection suggested that 3H-lysine incorporation into histones exhibited no major variations concurrent with the changes of host-cell DNA synthesis. In contrast, herpes simplex virus type 1 was found progressively to extinguish histone synthesis in the course of the cellular infection. Furthermore, histone synthesis in phosphonoacetic acid-treated cytomegalovirus-infected cultures was not enhanced over that in mock-infected controls. These observations do not support the view that human cytomegalovirus induces host-cell DNA replication under the conditions used. PMID- 6247633 TI - [Endocrine syndromes caused by receptor alterations]. PMID- 6247632 TI - Genetics and molecular biology of Streptomyces bacteriophages. PMID- 6247634 TI - Varicella immunity in adults. PMID- 6247635 TI - Clinically unsuspected insulinoma. PMID- 6247636 TI - A comparison of the beta-adrenergic receptor of the turkey erythrocyte with mammalian beta1 and beta2 receptors. PMID- 6247637 TI - A crystallographic, conformational energy, and biological study of Actodigin (AY 22,241) and its genin. PMID- 6247631 TI - 5'-terminal cap structure in eucaryotic messenger ribonucleic acids. PMID- 6247638 TI - Calcium-regulated modulator protein interacting agents inhibit smooth muscle calcium-stimulated protein kinase and ATPase. PMID- 6247639 TI - Xanthines and skeletal muscle: lack of relationship between phosphodiesterase inhibition and increased twitch tension in rat diaphragms. PMID- 6247640 TI - Changes in motochondrial calcium metabolism after treating mastocytoma cells with N6,O2'-dibutyryladenosine 3',5' cyclic monophosphate. AB - Comparison of Ca2+ uptake by isolated mouse liver mitochondria, and mitochondria prepared from mastocytoma cells grown with and without N6,O2'-dibutyryladenosine 3',5' cyclic monophosphate (DB cyclic AMP) and theophylline showed several differences in their capacity to take up and retain calcium. In particular mitochondria from DB cyclic AMP-treated mastocytoma cells took up more Ca2+ than mitochondria from untreated mastocytoma cells. Ca2+ uptake by mitochondria from DB cyclic AMP-treated cells was also increased in the presence of oxalate whereas oxalate did not affect Ca2+ uptake by mitochondria from untreated mastocytoma cells and it reduced Ca2+ uptake by mouse liver mitochrondria. The results suggest that inhibiting the growth of mastocytoma cells with DB cyclic AMP alters their mitochondrial Ca2+ metabolism. PMID- 6247641 TI - Coenzyme A-synthesizing protein complex of Saccharomyces cerevisiae. AB - The coenzyme A-synthesizing protein complex (CoA-SPC) is a multienzyme complex of Saccharomyces cerevisiae (Bakers' yeast), which has a molecular weight in excess of 200,000 as determined by Sephadex G-200 column chromatography. This multienzyme complex, which is insoluble in the crude yeast cell lysate, has been purified 229-fold. A cellular component of the yeast cell lysate, referred to as t-Factor, with a molecular weight of 400-1000 and chloride ion are involved in the solubilization of CoA-SPC. The CoA-SPC requires L-cysteine, D-pantothenic acid and ATP as substrates. The terminal CoA-SPC-bound intermediate is dephospho CoA, which is subsequently phosphorylated and released from the complex as CoA. The sequence of reactions for the synthesis of CoA by the CoA-SPC differs significantly from those previously proposed for other systems. It could be that the reaction sequence is unique for the yeast cell. PMID- 6247642 TI - On the mechanism of action of the phagocytosis-stimulating peptide tuftsin. AB - Incubation of human polymorphonuclear leukocytes (PMNL) or thioglycollate stimulated mouse peritoneal macrophages with the phagocytosis-stimulating peptide, tuftsin (2.5 X 10(-7) M, at 37 degrees C), caused an increase of 80-90% in intracellular cGMP levels, accompanied by a decrease of 20-25% in intracellular cAMP levels. Significant changes in cyclic nucleotide levels were detectable after 4 min of incubation, were maximal at 10-20 min and persisted for at least 60 min. The concentration dependences of the stimulatory effect of tuftsin on modulation on intracellular levels of cyclic nucleotides and on phagocytosis are similar, suggesting a cause and effect relationship between the two phenomena. This notion is further supported by the finding that 8-Br-cGMP and 8-Br-cAMP elicit stimulatory and inhibitory effects on macrophage phagocytosis, respectively. Measurement of 45Ca2+ influx into PMNL and macrophages in the presence and absence of tuftsin did not reveal any change in 45Ca2+ uptake from the media. However, tuftsin did enhance release of 45Ca2+ from cells preloaded with the isotope. Results suggest that modulation of both the amount of cell associated 45Ca2+ and the intracellular levels of cyclic nucleotides are key steps in the mechanism by which tuftsin augments phagocytosis. PMID- 6247643 TI - Light and GTP effects on the turbidity of frog visual membrane suspensions. AB - The time course of turbidity changes of frog visual membranes, dependent on osmotic shocks, on light and on nucleotide substrates or effectors of enzyme activities, were measured as absorption changes in a rapid mixing stopped-flow spectrophotometer. As a result of studies on different preparations, it is concluded that light can cause both rapid (within 50 msec) and slow (within 90 sec) changes in the turbidity of visual membranes, not associated with permeability changes, and that they are affected by GTP or its analog guanyl-5' yl imidodiphosphate; however, the light and GTP effects are lost when a water soluble fraction containing the light-sensitive enzyme cGMP-phosphodiesterase, is removed from the rod outer segments membranes. It is suggested that the fast light and GTP-sensitive response is related to the activation of cGMP phosphodiesterase. PMID- 6247644 TI - [Absorption spectra and magnetic circular dichroism of heme-containing proteins in nonequilibrium states. VI. Cytochrome c-oxidase]. AB - Low temperature (77 degrees K) absorption spectra of nonequilibrium states of cytochrome c oxidase produced by reduction of oxidases form protein by thermolysed electrons at 77 degrees K was studied. During reduction of cytochrome oxidase water-glycerol solution by thermolysed electrons at 77 degrees K a nonequilibrium reduced protein is formed. Low temperature (77 degrees K) absorption spectra of the nonequilibrium cytochrome oxidase differs from those reduced by ditionite. It was shown that the oxidation state of cytochrome a3 or addition of cytochrom c have no influence on these spectral changes. It is assumed, that the observed effects are conditioned by structural differences of reduced and oxidased cytochrome oxidase active center. Similar spectral changes were observed for cytochrome oxidase, bound to the mitochondrial membrane. At temperature increasing the low temperature reduced protein is relaxed to a corresponding equilibrium state. The spectral properties of bacterial cytochrome oxidase M. lysodeicticus do not depend on the way of reduction (by dytionite or thermolysed electrons at 77 degrees K). PMID- 6247645 TI - [Stepwise synthesis of oligonucleotides. XXVIII. Synthetic activity of S protein]. PMID- 6247646 TI - [Pyridoxalphosphate-modified derivatives of cytochrome c. Mono- and disubstituted derivatives: characteristics and effect on electron transport in cytochrome c depleted mitochondria]. AB - Cytochrome c is modified by covalent binding of pyridoxal phosphate (PLP) to lysine residues. One di-substituted [(PLP)2--C] and two mono-substituted derivatives [(PLP)--c and (PLP)''--c] were obtained and precisely purified. The peak at 695 nm and CD-spectra in 190--600 nm region show that all derivatives have native conformation. The differential UV-spectra of the derivatives against native protein show that in (PLP)2--c there is a contact dipole-dipole interaction between PLP chromophores. It is calculated that the N-atoms of the two PLP-substituted lysines must be at a distance less than or equal to 12 A. Analysing our and literature data, one may suppose that Lys-13 and Lys-87 are the most probable candidates for modification with PLP. (PLP)---c and (PLP)''--c behave differently during ion-exchange chromatography and when added to cytochrom c-depleted mitochondria. (PLP)''--c restores electron transfer at higher concentrations than (PLP)'--c. Both they restore fully succinate and ascorbate oxidation but at considerably higher concentrations than the native protein, i. e. modification of any one of the reactive towards PLP lysines descreases but does not exclude the interaction with its reductase and oxidase. The effective equilibrium constants of binding of modified derivatives to cytochrome c-depleted mitochondria are lower than the constant for native protein. Together with decrease in binding activity, Hill coefficients increase. From our results it may be supposed that probably the binding sites of cytochrome c for its reductase and oxidase partially overlap. PMID- 6247647 TI - [Study of intermolecular interactions and self-organization of adenylic nucleotides by the spin label method]. AB - A spin labeling method for obtaining thermodynamic parameters of nucleotide association is proposed. The method is based on the dependence of ESR parameters of the spin-labelled derivative on concentration of the nonlabelled compound due to formation of associates involving both spin-labelled and unmodified molecules. It is found that at pH 7.5 the constant of adenylic nucleotide association practically does not depend on the number of phosphate groups and is equal to 9.7 +/- 0.3 M-1 for AMP, ADP and ATP in 0.1 M NaCl at 28 degrees C. In acidic medium the value of the association constant increases by a factor two. Base stacking is shown to make the main contribution to stability of the associates of adenylic nucleotides at neutral pH, whereas upon base protonation the key role is played, apparently, by base-phosphate interaction. It is thought, that an increase in the solvent entropy is essential for stabilisation of the associates, this factor being more important in the case of nucleotide association as compared to the association of nucleosides. A possible role of nucleotide association in the processes of intracellular regulation is discussed. PMID- 6247649 TI - Exposure of rabbits to carbon monoxide and other gas phase constituents of tobacco smoke. AB - Non cholesterol-fed rabbits were exposed to carbon monoxide at concentrations in air of either 200, 2000, or 4000 ppm (= 0.02, 0.2, or 0.4% vol/vol). Further, exposure was performed to 0.5 ppm hydrogen cyanide alone or in combination with 200 ppm carbon monoxide or with 200 ppm carbon monoxide and 5 ppm nitric oxide and eventually to 50 ppm carbonyl sulphide. Duration of the continuous exposures were between 1/2 week and 12 weeks. Using the same criteria for intimal damage as in earlier morphological studies, no histotoxic effect on intimal/subintimal morphology of coronary arteries or the aorta could be demonstrated, when light microscopic evaluation was performed blindly. PMID- 6247648 TI - [Physical map of the DNA of bacteriophage phiB]. AB - A physical map of DNA phi B bacteriophage was constructed. Using the data of denaturation maps and heteroduplex analysis the positions of 10 (from 11) peaks were estimated. These peaks belong to DNA regions obtained after hydrolysis of phi B DNA by EcoRI endonuclease. This map is orientated to the end of the DNA molecule, which first entered the head, during phage maturation. The disposition of AT-enriched regions of the DNA molecule were shown. PMID- 6247650 TI - The synergistic effects of SV40 and BUdR on induction of gene mutations and chromosomal aberrations in Chinese hamster cells. AB - The induction of chromosomal aberrations and gene mutations was studied in Chinese hamster cells after separate and combined treatment with BUdR and SV40. Separate treatment of cells with BUdR or virus infection increased the yield of chromosomal aberrations and reversions from glutamine requirement, expressed at 40 degrees C (a ts mutant), to prototrophy. The combined effect of the incorporation of BUdR into one DNA strand, and a subsequent infection by SV40 was additive as regards the percentage of aberrant metaphases. The integration of the analogue into both DNA strands followed by SV40 treatment resulted in a statistically significant increase in the frequency of aberration carrying metaphases, as compared with the frequency expected if the two agents had acted additively. The same phenomenon was detected when the frequency of reversions to glutamine independence was studied. Hence, the effect of the joint treatment by BUdR incorporated into both DNA strands and SV40 was synergistic. This is known to characterize the effect of BUdR on virus-induced transformation. Therefore, obviously the agent that enhances the malignant transformation of cells by the virus similarly modifies its mutagenic activity. The results obtained are presumed to confirm the previously advanced hypothesis that the same events following infection might control both the integration of viral DNA into the host cell chromosome (and hence cell transformation) and virus-induced mutagenesis. The role of repair processes in the synergistic effect of BUdR and SV40 in the yield of reversions to glutamine independence is discussed. PMID- 6247651 TI - The activity of ketoconazole in mixed cultures of fungi and human fibroblasts. PMID- 6247652 TI - Normobaric oxygen toxicity of the lung. PMID- 6247653 TI - Fatal infectious mononucleosis. PMID- 6247655 TI - Nocturnal asthma and changes in circulating epinephrine, histamine, and cortisol. PMID- 6247654 TI - Defect of receptor-cyclase coupling protein in psudohypoparathyroidism. AB - Hormone-sensitive adenylate cyclase contains a recently discovered protein component that is required for stimulation of cyclic AMP synthesis by hormones and guanine nucleotides; the component presumably couples the membrane receptor to the cyclase. We studied this protein (termed "N") in erythrocyte membranes of patients with pseudohypoparathyroidism, using assays of the protein's biochemical activity and of its susceptibility to radiolabeling in the presence of [32P]NAD and cholera toxin. By both assays, the protein's activity was reduced by 40 to 50 per cent in erythrocytes of five of 10 patients with Type I pseudohypoparathyroidism as compared with those of normal and hypoparathyroid subjects and one patient with Type II pseudohypoparathyroidism. If activity of the N protein is reduced in other tissues, this deficiency could cause the resistance of target organs in pseudohypoparathyroidism to parathyroid hormone and other hormones that work via cyclic AMP. Erythrocytes of five patients with Type I pseudohypoparathyroidism, all in one family, showed no defect in activity of the N protein; the biochemical defect of this family remains undefined. PMID- 6247656 TI - Carbimazole and the autoimmune response in Graves' disease. AB - Microsomal antibodies and antibodies directed toward the receptor for thyroid stimulating hormone (TSH) decreased in parallel while patients with Graves' disease were taking carbimazole, whereas no significant changes were observed during treatment with placebo or propranolol. The changes in autoantibody levels during carbimazole treatment were independent of changes in serum thyroxine and could have been due to a direct effect of the drug on autoantibody synthesis. Evidence for this suggestion was provided when low doses of methimazole (the active metabolite of carbimazole) were found to inhibit thyroid-autoantibody production in cultured lymphocytes. Since thyroid lymphocytes are probably a major site of thyroid-antibody synthesis in Graves' disease and methimazole is concentrated in the thyroid during treatment, a local action of the drug on antibody production seems likely. This possibility could be important in the use of carbimazole to control hyperthyroidism. PMID- 6247657 TI - Dexamethasone in nonsuppressible Cushing's disease. PMID- 6247658 TI - Transduction and encoding mechanisms in muscle spindle. PMID- 6247659 TI - Genetic retrieval of viral genome sequences from herpes simplex virus transformed cells. AB - Oncogenic transformation of cultured cells by inactivated herpes simplex virus (HSV) types 1 and 2 has been demonstrated. Expression of HSV information in these transformed cells has been shown by immunofluorescence studies, detection of HSV neutralizing antibody in sera from tumour-bearing animals and by hybridization of HSV-specific RNA. Molecular hybridization studies of DNA from HSV-2 transformed hamster cells have detected up to 40% of the HSV genome present in several copies. Complementation of three HSV-2 temperature-sensitive mutants when superinfecting the RE1 rat embryo cell line (transformed by the HSV-2 temperature sensitive mutant ts1) suggests that resident viral genes can be expressed. Brown et al. used a similar approach to detect HSV information latent in human ganglia. We report here retrieval of intertypic HSV recombinants from HSV transformed cells after superinfection with ts mutants of the alternative serotype of HSV. Restriction enzyme analysis which clearly differentiates between HSV-1 and HSV-2 DNA has demonstrated the isolation of recombinants spanning the genome and of virus indistinguishable from the original transforming virus. PMID- 6247660 TI - Pharmacological evidence for a functional role of the prejunctional alpha adrenoreceptor in noradrenergic neurotransmission in the conscious rat. PMID- 6247661 TI - An improved assay of cyclic 3',5'-nucleotide phosphodiesterases with QAE-Sephadex columns. AB - A method for the assay of cyclic nucleotide phosphodiesterases is described which employs chromatographical separation of cyclic nucleotides and nucleosides on QAE A-25 Sephadex columns and 5'-nucleotidase as an auxiliary enzyme. The assay allows quantitative recovery of adenosine, guanosine and their metabolites from the anion exchanger and thus is suitable for use in crude phosphodiesterase preparations containing purine catabolizing enzymes. In comparative studies, this method was found to be considerably more sensitive than previous reported methods because of lower assay blanks and higher recoveries of the nucleoside catabolites. The method is suitable for kinetic analysis of crude enzyme preparations from micromolar to millimolar substrate concentrations. PMID- 6247662 TI - [Myopericarditis caused by Coxsackie B virus]. PMID- 6247663 TI - [Primary syphilis with symptoms of hepatitis]. PMID- 6247664 TI - Hypercalciuric rickets: a rare cause of nephrolithiasis. AB - An unusual case of rickets associated with hypercalciuria is described. In addition to proteinuria, the patient had phosphaturia, aminoaciduria, renal glucosuria and impaired renal concentration but no renal tubular acidosis. Studies did not support the diagnosis of primary hyperparathyroidism. The findings in the patient were very similar to those in 4 previously reported cases and are suggestive of a new combination of multiple renal tubular defects. PMID- 6247665 TI - Heparin-induced hyperkalemia: report of a case. AB - A 77-year-old diabetic man with a creatinine clearance of 23--27 ml/min developed hyperkalemia while receiving heparin for peripheral arterial insufficiency. Discontinuation of this agent led to resolution of hyperkalemia as the plasma aldosterone concentration multiplied by sixfold. Renal insufficiency may have predisposed this patient to the development of hyperkalemia when heparin therapy suppressed aldosterone synthesis. PMID- 6247666 TI - In vitro regulation of ACTH release from neurointermediate lobe of rat hypophysis. III. Effect of potassium (K+), calcium (Ca++) and dibutyryl cyclic 3',5'-adenosine monophosphate (dbc-AMP). AB - Alterations in the ionic composition of the medium and different secretagogues have been used in order to study the mechanism of release of ACTH from superfused neurointermediate lobes (NIL) of rat hypophysis. We showed that: (a) a tenfold increase of K+ in the medium caused a reversible and repeatable stimulation of the ACTH release; (b) removal of Ca++ reversibly abolished the stimulating effect of high K+; (c) removal of Ca++ had no effect on the stimulating effect of a hypothalamic extract (HE); (d) in the latter case, a reversible significant weakening was obtained by the addition of EDTA in the Ca++-free medium; (e) dbc AMP caused a reversible and repeatable stimulation of the ACTH release; (f) comparable results were obtained for anterior lobes (AL) superfused in the same conditions. From these data we can conclude that Ca++ is necessary for the stimulation of the hormonal release and that factors such as K+ or dbc-AMP can mimic the in vitro stimulating effect of a HE. Similarities, which appear in this study, between the modulation of the ACTH release from NIL and AL, led us to support the idea that, in vivo, a release of ACTH from the NIL, may occur in physiological conditions. PMID- 6247667 TI - Neonatal monosodium glutamate. Effects upon analgesic responsivity and immunocytochemical ACTH/beta-lipotropin. AB - Neonatal administration of monosodium glutamate (MSG) produces neurotoxic degeneration of the retina and medial-basal hypothalamus, including the arcuate nucleus. Since this hypothalamic area contains the only neuronal cell bodies in brain which contain adrenocorticotrophic hormone (ACTH) and beta-lipotropin (beta LPH) and beta-endorphin, destruction of these cells by MSG may interfere with pain responses mediated by nerve fibers arising from these perikarya. The present study examined whether MSG-treated rats, as compared to littermate controls, exhibited concomitant changes in the immunocytochemical distribution of ACTH and beta-LPH, and their reactivity to several analgesia-inducing manipulations. Although MSG-treated rats did not differ from control rats in their baseline reactivity to electric shock, they displayed an inability to exhibit analgesia following acute exposure to cold-water swim stress. In addition, MSG-treated rats showed an attenuated analgesic response following morphine administration. However, the analgesia elicited by either abrupt food deprivation, or the glucoprivic stress of 2-deoxy-D-glucose, was unaffected by neonatal MSG treatment. Concomitant with these selective analgesic deficits, MSG-treated rats displayed a marked immunocytochemical reduction in ACTH/beta-LPH perikarya and terminals in brain, but not pituitary. These data indicate that multiple pain inhibitory systems exist, and that some rely upon an intact medial-basal hypothalamus to produce analgesia. PMID- 6247668 TI - Specific hormonal and neurochemical responses to different stressors. AB - The neuroendocrine and neurochemical responses of rats to 5 min of cold exposure versus 5 min of forced immobilization were determined and compared. We found that plasma hormones and brain neurochemical systems responded differently to the two different stressors. Plasma prolactin levels were elevated over 10-fold in the immolilized group, while rising only 2-fold in the cold stress group. Levels of corticosterone were significantly increased and growth hormone levels were decreased in both stressed groups as compared to controls. Levels of cyclic GMP were markedly elevated in 11 brain regions following cold exposure. Surprisingly, no elevation of cyclic GMP was found after forced immobilization. Cyclic AMP, norepinephrine, and dopamine levels throughout the 17 regions of brain examined showed no significant response to 5 min of either stressor. Lesions of the ventral medial tegmental area did not affect the cyclic GMP or neuroendocrine responses to cold stress. Lesion of the nucleus locus ceruleus did not affect the cyclic GMP response but significantly reduced growth hormone levels in the cold stressed rats. PMID- 6247669 TI - Temporal relationships between the circadian rhythmicity in plasma levels of pituitary hormones and in hypothalamic concentrations of releasing factors. AB - Ovariectomized female rats were implanted with estradiol containing silastic implants to induce constant circulating levels of the steroid, and sacrificed every 2 h in order to determine neuroendocrine rhythms. Under these conditions, we observed very marked circadian fluctuations in the hypothalamic concentrations of corticotropin-releasing factor (CRF), luteinizing hormone-releasing hormone (LHRH) and thyrotropin-releasing hormone (TRH), and in plasma levels of adrenocorticotropin (ACTH), corticosterone, luteinizing hormone (LH) and prolactin; the amplitude of the prolactin cycle was in particular much higher than in non-chronically estrogenized animals. The daily variation in CRF, ACTH and corticosterone showed significant rank correlations. Changes in hypothalamic content of LHRH and TRH were biphasic; the increase observed during the light period was abruptly interrupted by a depletion episode, coincident with the period of maximal LH and prolactin secretion, respectively. The initial phase of ACTH, LH and prolactin increments occurred between 11.00 and 15.00 h, and was relatively well synchronized. The steepest rise in ACTH and prolactin occurred at the same time, and preceded that of LH by a constant lag of about 2 h. After that initial period, secretion kinetics of the three hormones followed an independent pattern. The data suggest that increased secretion of several hormones results from activation of neural mechanisms occurring within a limited period of the 24 hour cycle. PMID- 6247671 TI - Selective decline in cellular immune response to varicella-zoster in the elderly. AB - The incidence of herpes zoster rises markedly in the aged. We evaluated the hypothesis that cellular immunity to varicella-zoster (VZ) viral antigens may be impaired in aged subjects. We found that the lymphocyte proliferation to VZ antigen was less in older asymptomatic individuals than in normal young controls. In contrast, responses to other antigens did not differ. Antibody titers to VZ were similar in both young and old subjects. Impairment of cellular immunity to VZ, on a population basis, may contribute to the increased risk of herpes zoster in the elderly. PMID- 6247672 TI - Eaton-Lambert syndrome and malignant thymoma. AB - Eaton-Lambert syndrome is most frequently associated with small-cell carcinoma of the lung. We describe the first case of this disorder in a patient with malignant thymoma. Guanidine treatment had no clinical or electrophysiologic effects. PMID- 6247670 TI - Influence of ACTH on phosphorylation of ribosomal proteins from rat adrenal glands. PMID- 6247673 TI - Cell-mediated immunity to polio and HLA antigens in amyotrophic lateral sclerosis. PMID- 6247675 TI - [Peripheral neuropathies. A social problem of importance for WHO, FAO and UNESCO]. PMID- 6247674 TI - [Effect of circulatory hypoxia on the activity of protein kinases in the subcellular fractions of rabbit brain]. PMID- 6247676 TI - [Metabolic properties of Hurthle cell adenoma]. PMID- 6247677 TI - Does pyridoxal phosphate have a non-coenzymatic role in steroid hormone action? PMID- 6247678 TI - Hilar cell tumor of the ovary: preoperative localization by selective retrograde venous sampling. AB - A well-documented case of hilar cell tumor of the right ovary in a postmenopausal patient is described. Pre-operative retrograde venous catheterization and sampling were used to localize this virilizing tumor. PMID- 6247679 TI - Evaluation of 9-0 polyglycolic acid and polyglactin suture in rabbit limbal wounds. AB - Sutures of 9-0 polyglycolic acid (Dexon) or polyglactin (Vicryl) were used to close limbal incision in rabbit eyes. The handling properties of both sutures were excellent and tissue reaction minimal. The majority of sutures disappeared four to six weeks postoperatively. Small areas of anterior wound gaping without leak occurred in half the eyes. While the performance of this suture was superior to that of 10-0 synthetic absorbables studied previously, it is advised that clinical application be approached with caution. PMID- 6247680 TI - Antimetabolite drug therapy in herpes simplex. AB - Idoxuridine (IDU) and adenine arabinoside (Ara-A) are less than ideal drugs for the treatment of herpes because of toxicity, only partial efficacy with initial dendritic ulcers, and insufficient antiviral activity to prevent occasional epithelial breakthrough. Trifluorothymidine (TFT), soon to be released by the FDA for general use, appears to be more effective, curing 97% of ulcers in two weeks, and healing large ameboid ulcers more rapidly. Acycloguanosine, in combination with Ara-A, virtually eliminates stromal disease in rabbit eyes. A major advantage of this drug is its apparent lack of systemic toxicity due to its ability to interfere with the replication of virus-infected cells while not harming normal cells. Acycloguanosine should be available as an orally active, highly effective antiviral agent that can be given on an outpatient basis to treat deep infections. A new approach to the prevention of herpes recurrence involves the recognition that some isolates of herpes are mild or avirulent. Initial infection with avirulent virus may protect against virulent infection and yet may not cause disease. If such differences in virulence can be correlated with biochemical differences among the strains, prevention and treatment of herpes may be possible through manipulation of these metabolic pathways or immunization with avirulent virus. PMID- 6247681 TI - Neural tumors of the oral cavity. A review of the spectrum of benign and malignant oral tumors of the oral cavity and jaws. AB - The clinical and histologic features of benign and malignant neural tumors of the oral cavity and jaws are reviewed. Some rarer histologic variants are mentioned. Particular attention is paid to the two syndromes involving neural tumors of the oral cavity, namely, neurofibromatosis and multiple endocrine neoplasia III. A previously unreported case of the latter is presented. PMID- 6247682 TI - Adenocystic carcinoma in computed tomography. AB - Computed tomography was introduced in 1972 by Ambrose and Hounsified in England. At first it was designed for diagnostic radiology and neurosurgery of the brain and skull. Soon, in 1974, whole-body computerized tomography scanners went into operation in the United States and then came into worldwide use. The use of computed tomography in maxillofacial regions is rare. In the report two adenocystic carcinomas in the maxilla are described by computed tomography, and the images thus produced are compared to those obtained by ordinary tomography and isotope scintigraphy. PMID- 6247683 TI - [Herpes immune complex nephritis]. PMID- 6247684 TI - [Organizational problems and rehabilitation facilities at after-care centers based on a national survey]. PMID- 6247685 TI - Primary oat cell carcinoma of the larynx. PMID- 6247686 TI - Neutrophil dysfunction associated with states of chronic and recurrent infection. AB - Infants, children, and young adults who suffer chronic and recurrent bacterial or fungal infection despite adequate numbers of circulating granulocytes and normal or elevated levels of immunoglobulins should be suspected of having fundamental defects in granulocyte functioning. This article considers clinical disorders for which there is evidence for associated defects of polymorphonuclear leukocytes. PMID- 6247687 TI - Erythrocyte enzyme disorders in children. AB - Erythrocyte metabolic abnormalities should be considered as a possible cause of hemolysis when there is no evidence of an immune-mediated hemolytic anemia, no consumptive red blood cell disorder, no morophologic or laboratory data to suggest a problem of the red cell membrane, and no evidence of a quantitative or qualitative defect in hemoglobin synthesis. Glucose-6-phosphate dehydrogenase deficiency is clearly the most common enzyme deficiency causing clinical problems. PMID- 6247688 TI - [Radioisotope evaluation of the functional state of the liver in women with prenatal death of the fetus]. PMID- 6247689 TI - Effect of calciotropic hormones and cyclic nucleotides on aminoaciduria and phosphaturia. AB - Parathyroid extract (PTE), dibutyrylcyclic AMP (dbcAMP), adenosine cyclic 3':5' monophosphate (cAMP). calcitonin (CT), and calcium chloride were infused separately into anesthetized, sham-operated, or TPTX vitamin D-fed adult rats to examine the effect of these calciotropic agents on fractional excretion (FE) of alpha-aminoisobutyric acid (AIB), and phosphate anion (Pi). AIB is a nonmetabolizable amino acid. Inulin clearance, FEAIB, and FEPi were stable in the intact (n = 10) and TPTX rat (n = 10). TPTX decreased FEAIB, and FEPi significantly (P less than 0.001 for both). PTE and dbcAMP both increased FEAIB in the intact rat (P less than 0.001); failure to obtain this response in the TPTX animal was a key finding. PTE and dbcAMP increased FEPi (P less than 0.001) in both the intact and TPTX animal. CT was the only agent (versus PTE, dbcAMP, adenosine cyclic 3':5'-monophosphate, and CaCl2) to increase FEAIB (P less than 0.001) in the TPTX rat; furthermore, it was the only agent that did not increase FEPi in the TPTX rat although it had hypocalcemic and hypophosphatemic effects. Changes in inulin clearance or plasma concentration of AIB, following infusion of calciotropic agents, do not explain the unique responses in FEAIB in the TPTX rat. Our findings suggest that hyperaminoaciduria induced by parathyroid hormone and cyclic nucleotide in the intact animal may be mediated by CT. Hyperphosphaturia is not a necessary response to small-dose (25 milliunits/kg.hr) infusions of CT. PMID- 6247690 TI - Enhanced adenosine 3':5' - monophosphate response to beta-adrenergic stimulation in cystic fibrosis fibroblasts after removal of conditioned medium. AB - Skin fibroblasts derived from 6 patients with cystic fibrosis (CF), 1-6 months old, and from 6 age matched donors were investigated for their ability to accumulate cyclic adenosine 3':5'-monophosphate (c-AMP) in response to isoproterenol and prostaglandin E1 (PGE1) using strictly defined culture conditions. In order to obtain, as far as possible, constant protein content and cell number, cultures were synchronized in the early G1 phase of the cell cycle by growing them in serum free medium before adding stimulating drugs. There were no statistically significant differences both in basal c-AMP or after incubation with theophylline alone. When cultures were thoroughly washed prior to stimulation, c-AMP accumulation in response to isoproterenol was consistently higher (p less than 0.001) in CF than in normal fibroblasts, whereas response to PGE, did not differ significantly. This difference in response cannot be attributed to differences in dose- or time-response curves, or to differential escape of cAMP into the culture medium. Returning the conditioned media (CM) to the cultures after the washing procedure, or omitting the washing procedure altogether, normalized the cAMP response of CF cells. These data indicate that CF fibroblasts "delete" or "add to" the conditioned medium a substance when washed out of the cultures leave the cells hypersensitized to beta-adrenergic stimulation. PMID- 6247691 TI - A new variant of galactosemia: galactose-1-phosphate uridylytransferase sensitive to product inhibition by glucose 1-phosphate. AB - In the erythrocytes of a patient with the clinical symptoms of galactosemia, a galactose-1-phosphate uridylyltransferase with abnormal kinetics was observed. Under standard assay conditions, the uridylyltransferase activity was almost normal initially and became completely inactivated within 30 min. The abnormal kinetics could be ascribed to a product inhibition by glucose 1-phosphate. The inhibition was produced by a variety of sugar phosphates, the most potent of which proved to be glucose 1-phosphate, mannose 1-phosphate, and fructose 6 phosphate. The variant galactose-1-phosphate uridylyltransferase was further characterized by a lowered affinity towards galactose 1-phosphate, non-Michaelis Menten kinetics towards UDP-glucose, an increased thermal stability, and complete inactivity upon Cellogel electrophoresis. PMID- 6247692 TI - [Intestinal enzymatic activity as an index of the functional state of the intestines in premature infants]. PMID- 6247693 TI - The significance of the absent member in milieu therapy. PMID- 6247694 TI - Organochlorine pesticide, PCB, and PBB residues and necropsy data for bald eagles from 29 states--1975-77. AB - During 1975-77, 168 bald eagles (Haliaeetus leucocephalus) found moribund or dead in 29 states were analyzed for organochlorine pesticides and polychlorinated biphenyls (PCBs); 32 specimens from 13 states were analyzed for polybrominated biphenyls (PBBs). PCBs were present in 166 bald eagle carcasses and DDE was found in 165. TDE and dieldrin were identified in 137 samples, trans-nonachlor in 118, and oxychlordane in 90. Brains of five eagles contained possible lethal levels of dieldrin, and two eagles possibly died of endrin poisoning. Nine eagle livers, analyzed because of suspected lead poisoning, contained high levels of lead. Twenty percent of the eagles died from shooting, the most common cause of death; this cause of death, however, has declined. PMID- 6247695 TI - Do sympathetic preganglionic neurones have a recurrent inhibitory mechanism? AB - In anaesthetized and immobilized cats 32.5% of the intermediolateral sympathetic preganglionic neurones (B2-SPN) in T3, T8-9 and L2 spinal segments can be re excited antidromically by repeated stimuli only at very long interstimulus intervals (16 ms and more) considerably exceeding the refractoriness of the somata and axons of these neurones. This was observed in the absence of any association with subnormality or other peculiarities B2-SPN axons. In this group of B2-SPNs with prolonged time interval between repeated antidromic discharges, orthodromic spikes effectively inhibited the generation of antidromic ones for a period which was substantially longer than the possible collision time. The preceding antidromic activation of a fraction of the B2-SPN segmental pool partly inhibited the orthodromic reactions of the others in this segmented elicited by stimulation of segmental afferent fibres or spinal descending pathways. These data definitely indicate that some of the B2-SPN group have a recurrent inhibitory mechanism. PMID- 6247696 TI - Pathways mediating optokinetic responses of vestibular nucleus neurons in the rat. AB - 1. The effects of various brain lesions on the responses of vestibular nuclear neurons (Vn) of the horizontal semicircular canal system to optokinetic stimulations were studied to elucidate the optokinetic path from the retina to the vestibular nuclei. A previous study performed in intact rats served as a control [2]. 2. It was shown that the pretectal region including the n. of the optic tract is the first central relay in the optokinetic path; it receives its functionally effective input from the contralateral eye. Unilateral lesions of this area rendered all Vn responses unidirectional when tested with binocular stimulation. Lesions of other visual centers such as the superior colliculi or visual cortices had no influence on the optokinetic response properties of Vn. 3. The area of the n. reticularis tegmenti pontis (NRTP) proved to be an important link between pretectum and vestibular nuclei: Unilateral lesions produced effects similar to those described for pretectal lesions. Pretectal axons to NRTP descend lateral to the MLF and tectospinal tract. 4. It was demonstrated that the vestibular commissure plays the crucial role in mediating the mirror image optokinetic effects to Vn on the opposite side and assures the bidirectionality of the responses to binocular stimulation. 5. Cerebellectomy did not significantly affect the Vn responses to the optokinetic stimuli presented in this study. 6. Electrical stimulation of the pretectum excited type II and inhibited type I Vn ipsilaterally and had the opposite effect on Vn located on the opposite side. NRTP stimulation excited type II and inhibited type I ipsilaterally; latency analysis of these effects suggested that the pretectal stimuli excited opsilateral NRTP neurons which, in turn, excited ipsilateral type II Vn. Ipsilateral type I inhibition as well as the concurrent contralateral type II inhibition and type I excitation are produced by the inhibitory action of type II on type I and the commisural system. 7. Systemic application of picrotoxin abolished all optokinetic responses of Vn except the type II activation. This finding further supports the hypothesis described above. 8. Unilateral pretectal or NRTP lesions abolished OKN to surround motion in the direction of the lesion. PMID- 6247697 TI - Optokinetic responses of vestibular nucleus neurons in the rat. PMID- 6247698 TI - Solubility of inert gases in dog blood and skeletal muscle. AB - Solubility of H2, Ar, CH4 and SF6 was determined at 310 K (37 degrees C) in water, in saline (0.154 mol NaCl/l H2O), in plasma and whole blood of dogs, and in homogenates of the dog gastrocnemius muscle. The liquids were equilibrated with pure gases, and the dissolved gases were extracted and measured by gas chromatography as described previously (Meyer, M.: Pflugers Arch. 375, 161--165, 1978). In saline, the solubilities were 4% (SF6) to 15% (Ar) lower than in water. For dog blood the following mean values for the solubility coefficient (in mumol . 1(-1) . kPa-1) were found: for H2, 6.44; for Ar, 9.94; for CH4, 11.44; for SF6, 2.62. The red cell/plasma and the muscle/blood solubility ratios were near unity for H2, Ar and CH4 (ranging from 0.9 to 1.3); for SF6, however, they were much higher (about 2.1), apparently due to the high solubility of SF6 in hydrophobic substances (lipids). PMID- 6247700 TI - Features of adipocyte sensitivity to lipolytic agents in spontaneously hypertensive rats. Possible role of altered intracellular calcium distribution. PMID- 6247699 TI - Effects of a chronic corticotropin treatment on brown adipose tissue of cold acclimated rats. PMID- 6247701 TI - [Value of the estimation of gliofibrillary acid protein in the diagnosis of glial tumours (author's transl)]. AB - Glial Fibrillary Acidic Protein (G.F.A.P.) is characteristic of astrocytes. Its estimation in a tumour fragment removed surgically may be used to confirm whether or not a cerebral tumour is glial in nature. This was confirmed here by study of 6 cases. G.F.A.P. levels were normal only in the 2 patients whose cerebral tumours were not glial. It remains to be determined whether this estimation may be used to define a particular treatment or prognosis. PMID- 6247702 TI - [The treatment of peripheral neuropathies in a case of IgA myeloma and one of mixed cryoglobulinaemia. Repeated plasmapheresis (author's transl)]. AB - Peripheral neuropathies were the presenting feature of an IgA lambda myeloma in a 61-year-old man and a mixed cryoglobulinaemia in a 46-year-old woman. A spectacular improvement in these symptoms followed treatment including large volume plasma exchanges with appropriate chemotherapy. This efficacy of repeated plasmapheresis leads to a discussion of the possible mechanisms of these neuropathies. PMID- 6247703 TI - [Level of cyclic AMP in cerebrospinal fluid during a meningeal hemorrhage]. PMID- 6247704 TI - [Isolation of an Herpes simplex virus type 2 from a human cervical cancer by means of a cell cocultivation]. PMID- 6247705 TI - Specialised diets: spread the word! PMID- 6247706 TI - [Role of prolactin in the growth of prostatic neoplasms]. PMID- 6247707 TI - Multiple sclerosing haemangiomas of the lung. AB - A case of mulitple sclerosing haemangiomas of the lung is described from a 40 year-old woman, who presented with haemoptysis. A chest X-ray revealed multiple circumscribed coin lesions in both lungs. A right upper lobectomy was done for diagnosis. The patient has remained well for 2 years after surgery. Multiplicity of tumour masses of pulmonary sclerosing haemangiomas is extremely rare and, although benign, may pose a great diagnostic problem. PMID- 6247708 TI - [Clinical and evolutive characteristics of bronchial cancers discovered by systematic X-ray examinations (author's transl)]. AB - The characteristics of broncho-pulmonary cancers discovered during systematic X ray were studied over an 11 year period by comparison with cancers discovered through their symptoms. The operability of first group patients was definitely superior (62.5% against 36.7%y and so was the 5 year survival (18.7 against 5.5%). These differences are statistically significant and should be remembered, before the results of extensive anglo-saxon surveys be known, about the value of X-ray detection of bronchial cancer--at least in high risk patients. PMID- 6247709 TI - Purification of human myeloperoxidase by Concanavalin A-Sepharose affinity chromatography. AB - Myeloperoxidase (E.C. 1.11.1.7. Donor: H2O2 oxidoreductase), an enzyme of the azurophil granule of polymorphonuclear leukocytes, has been purified from the blood of a single human donor. Leukocytes were harvested by dextran sedimentation and contaminating erythrocytes were removed by hypotonic lysis. Myeloperoxidase was extracted from the leukocytes by dissolution in cetyltrimethyl-ammonium bromide (CETAB). The extract was adsorbed to a Con A-Sepharose gel, eluted with alpha-methyl-D-mannoside and rechromatographed on Sephadex G-200. Approximately 100% of the initial peroxidase activity was recovered in the final preparation, which was homogeneous by polyacrylamide disc gel electrophoresis at pH 4.5 and displayed the typical oxidized and reduced absorption spectra of purified myeloperoxidase. The oxidized enzyme showed a Soret maximum at 430 nm which shifted to 470 nm upon reduction. The molecular weight was estimated by G-200 Sephadex gel filtration chromatography to be 146,000 daltons. PMID- 6247710 TI - Freezing and thawing of myosin with no alteration in ATPase activity. AB - Myosin can be frozen in liquid nitrogen (-70 degrees C) and stored at this temperature for 5 months with no loss in K+, Ca2+, or actin + Mg2+ -stimulated ATPase activities. Furthermore, myosin can be refrozen and thawed in this manner for at least 5 consecutive times with no alteration in ATPase activity. PMID- 6247711 TI - Nutrition and cancer. PMID- 6247712 TI - Virology and cancer. PMID- 6247713 TI - [Levels of adenylic system components (ATP, ADP, AMP) and cAMP during development of Blastocladiella emersonii]. AB - Concentrations of ATP, ADP, AMP, cAMP as well as pyruvate and glucose-6-phosphate were measured in B. lastocladiella emersonii cells developing via RS morphogenetic pathway. They varied significantly in the course of development (1.3-14.8 mumole/g dry weight for the sum of ATP+ADP+AMP; 0.012-5.3 nmole for cAMP; 0.47-1.9 mumole for pyruvate; 0.36-4.78 mumole for glucose-6-phosphate). At the same time the adenylate energy charge remained essentially unchanged (about 0.8) from the middle of exponential growth till the end of the stationary phase. At the late stages of RS-sporangia formation the concentration of all the above compounds decreased by about 10 times, and the adenylate energy charge only by 30%. Positive correlation between the levels of ATP and cAMP in RS cells was demonstrated. The concentration of adenylic nucleotides and cAMP showed the most noticable changes at the end of exponential growth; transition of the point of no return was not accompanied by significant changes in the pools of adenylic system, cAMP or energy charge. PMID- 6247714 TI - [Thermostability of glucose oxidase immobilized on silica gel by different methods]. AB - Immobilization and thermostability of glucose oxidase immobilized on silica gel MCA-750 7 by different methods were studied. The process of inactivation was found to follow two stages that differed in their rate. The most stable preparations were produced by immobilization based on bromacetyl and glutaraldehyde methods. PMID- 6247715 TI - Chronic ACTH administration and the development of hypertension in rats. PMID- 6247716 TI - Chicken sarcomas and expression of chicken endogenous virus after transplantation of virus-free Rous hamster tumor cells. PMID- 6247717 TI - Pulmonary and systemic vascular responses to vasoactive agents after chemical sympathectomy. PMID- 6247718 TI - Growth and maintenance of normal prostatic epithelium in vitro--a human cell model. PMID- 6247719 TI - The Dunning tumors. AB - We have described the Dunning tumor, R3327, as a most useful model system in studies of human prostatic cancer. The tumor resembles the human disease in its histologic picture, ultrastructure, and most of its metastatic capabilities. The one exception to the latter is the apparent absence of metastatic lesions in the bone. Like the variability seen in human cancer of the prostate, the R3327 has been shown to develop multiple sublines, each with different histologic pictures, growth rate, and androgen dependence. Thus far the literature is replete with reports of the Dunning tumor as a model in hormonal, chemotherapeutic, and immunologic experiments. When we look at the results obtained in the five years since the Dunning tumor has been resurrected, we can be encouraged with what the future of prostatic cancer research holds with the use of this system. PMID- 6247720 TI - Synthesis of novel hexestrol and diethylstilbestrol derivatives as potential anticancer and estrogenic agents. AB - Two novel series of potential anticancer agents derived from hexestrol and diethylstilbestrol have been synthesized. The first includes several alkylating agents containing sulphonic esters and nitrogen mustard functions attached through various chains to only one phenolic group in hexestrol. The second contains the N1-acetyl-N4-substituted thiosemicarbazide moieties attached to one phenolic group hexestrol or to the two phenolic oxygens in diethylstilbestrol. The tests of some of the products for antileukemic activity in P 388 Lymphocytic Leukemia indicated no significant activity over the parent nuclei. The estrogenic activity of some representative examples of the thiosemicarbazides was found to be dependent on the nature of the N4-substituent in the thiosemicarbazide moiety. PMID- 6247721 TI - Heterogeneity of opiate-receptor interaction. AB - The results of many recent pharmacological studies demonstrate that opiates can interact with their receptors in a number of different ways. In vivo and in situ experiments indicate that presence of at least four different agonist interactions, while in vitro binding studies indicate that interactions may differ between agonists and antagonists as well. The available evidence suggests that at least two topologically distinct receptors exist, one which binds alkaloids preferentially and the other peptides, while conformational changes of the same receptor probably account for agonist-antagonist heterogeneity. We propose that the topologically distinct receptors can be seen as simply receptors of differing affinities for the endogenous peptides, and thus may serve to regulate the latter's effects at a wide range heterogeneity even at nanomolar concentrations of ligand, suggesting that many binding molecules may not be pharmacologically relevant receptors. PMID- 6247722 TI - Ornithine decarboxylase as a biological and pharmacological tool. AB - Ornithine decarboxylase, the initial enzyme in the polyamine biosynthetic pathway, is induced in target tissues in response to a variety of trophic agents including polypeptide and amine trophic hormones, cyclic AMP analogs, drugs, and trophic steroid hormones. The induction of ornithine decarboxylase in these systems is regulated at a transcriptional level and is proportional to the extent of stimulation. Because of its rapid half-life (10-20 min), a general maximum of induction is detectable within 4-5 h of stimulation, and its induction pattern can serve as a rapid, specific index of increased RNA and protein synthesis. Implications for its usefulness to pharmacologists, endocrinologists, physiologists, and biochemists are summarized. PMID- 6247723 TI - Age-related changes in the sensitivity of blood vessels to drugs. PMID- 6247724 TI - Toxicity of naturally occurring purine deoxyribonucleosides. PMID- 6247725 TI - New concepts of mechanisms of hepatocyte bile formation. PMID- 6247726 TI - Synaptic repression at neuromuscular junctions. PMID- 6247727 TI - Mechanism of glucose-induced insulin secretion. PMID- 6247728 TI - Control of plasma aldosterone in mammals. PMID- 6247729 TI - Tonic immobility and the alpha-adrenergic system in chickens. PMID- 6247730 TI - In vitro K+-effect on ATP and phosphocreatine levels and on Na+ K+-atpase activity of mouse brain cells. AB - Cell suspensions were prepared form mouse brain cortices. Cells were incubated in a medium also containing 10 mmol.l-1 glucose and either 5 mmol l-1 K+ or 50 mmol.l-1 K+ concentration. In order to standardize individual experiments, the biuret reaction was modified for rapid determination of the protein in cell suspensions. The cellular reserves of energy-rich phosphates were determined in the course of 60 min of cell incubation with 5 mmol.l-1 K+ and following 30 min incubation of cells with 50 mmol.l-1 K+. The level of ATP was significantly elevated after 10-60 min of incubation with low K+, from 0.58 to 0.78 micromoles per 100 mg protein; the creatine phosphate content during the same interval was in the range 1.27-1.44 micromoles per 100 mg protein. A significant decrease of energy reserves in cells was observed if the extracellular concentration of K+ was increased. After 10 and 30 min of incubation, a decrease by 36.2% and 38.5% for creatine phosphate and 34.6% and 44.9% for ATP was found, respectively. Na+ K+-ATPase activity of cells incubated for 60 min with 5 mmol.l-1 K+ was expressed as 4.99 micromoles of liberated Pi per 100 mg protein.1 h. Enzyme activity was stimulated with 50 mmol.l-1 K+ by 24.3% and 25.7% after 10 and 30 min of cell incubation respectively. Stimulation of Na+ K+-ATPase activity of brain cortex cells was directly dependent on the actual presence of stimulating 50 mmol.l-1 K+ concentration. PMID- 6247731 TI - The treatment of herpetic whitlow--a new surgical concept. AB - Characteristics of cutaneous lesions caused by herpes simplex virus (HSV-1) are: Acquired by skin-to-skin contact; humans are the only natural host. Often on the hands of health care personnel. Painful swelling, erythema, vesicles, and ulcerations. Possible involvement of cutaneous digital areas of paronychium, eponychium, and subungual matrix. Similar to a bacterial (septic) or fungal felon. Self-limiting--14- to 21-day course. An aseptic felon, which provides a contraindication to surgical incision and drainage of the deep pulp space. Severe pain: the major complaint from all patients. Relieved of pain by decompression of the involved nail bed, either by segmentally excising or perforating the overlying nail or both to unroof the vesicles. PMID- 6247732 TI - The role of urinary prostaglandin E and cyclic AMP in the polyuria of hypokalemia in rats. AB - The effect of potassium depletion on urinary prostaglandin E and cyclic AMP excretion was studied in female Sprague-Dawley and in Brattleboro rats. The animals were fed a potassium-free diet for 20 days which resulted in an average decrease in serum potassium of 25% in both strains. In the Sprague-Dawley rats, potassium depletion increased urine volume from 5.5 +/- 0.9 ml/day to 25.9 +/- 3.5 ml/day (p less than 0.001), decreased urinary osmolality from 1483 +/- 87 mosmol/kg H2O to 372 +/- 12 mosmol/kg H2O (p less than 0.001) and suppressed urinary cyclic AMP excretion from 56.95 +/- 3.81 nmoles/day to 0.83 +/- 0.40 nmoles/day (p less than 0.001). Potassium depletion in the Brattleboro rats did not affect these parameters. Excretion of prostaglandin E-like immunoreactivity in urine did not change in either strain with potassium depletion. The findings support the hypothesis that prostaglandins do not play a significant role in the polyuria caused by potassium deficiency in rats. Hypokalemia may cause polyuria by suppression of vasopressin-sensitive cyclic AMP generation, leading to a decrease in water permeability. PMID- 6247733 TI - Facilitating a therapeutic milieu in the families of schizophrenia. AB - For many years, mental health professionals and the families of schizophrenics have coexisted in an atmosphere of mutual distrust and hostility. In this paper, we would like to present some of our experiences in creating a more productive relationship with the families of long-term schizophrenic clients in an aftercare setting. We have found that it is possible to engage these families as allies in the long and difficult process of psychodynamically oriented psychotherapy and resocialization. In many instances, these families actually provide several of the major functions of a vital therapeutic milieu, including containment, support, and structure (Gunderson, 1978). PMID- 6247734 TI - Psychotropic drugs and taxonomic systems. AB - Attempts to underpin the classification of psychiatric drugs in biological and clinical terms are discussed with reference to their value and limitations. The current need for a multiplative, heuristic taxonomy is suggested. PMID- 6247735 TI - Neuroendocrine tests of monoamine function in man: a review of basic theory and its application to the study of depressive illness. AB - Neuroendocrine tests are now available for studying monoamine function in the brains of patients with mental illness. Great care is required in the selection of drugs which act upon specific monoamine receptors to produce specific hormonal responses. Equal care is required in the control of biological variables which may influence hormonal release. Recently reported neuroendocrine studies of depressive illness are assessed in these terms. The results of these studies support the hypothesis that there is defective noradrenergic function in the brains of some patients with depressive illness. PMID- 6247736 TI - Reduced activity of angiotensin-converting enzyme in basal ganglia in early onset schizophrenia. PMID- 6247737 TI - Prediction of clinical course of bipolar manic depressive illness treated with lithium. AB - A group of bipolar manic depressive patients attending a routine lithium clinic were investigated. The results suggest that, when on treatment with lithium, manic depressive patients with a good prognosis tend to have a higher erythrocyte Na-K ATPase and higher plasma and erythrocyte lithium concentrations than those with a poor prognosis. There was no evidence to suggest that the erythrocyte: plasma lithium ratio was useful in predicting clinical response to lithium therapy. There was also a positive correlation between plasma lithium concentration and Na-K ATPase activity, confirming that in manic depressive subjects lithium produces a rise in erythrocyte Na-K ATPase activity. PMID- 6247738 TI - Interaction of ambient temperature with the effects of delta 9 tetrahydrocannabinol on brain catecholamine synthesis and plasma corticosterone levels. AB - The effects of delta 9-tetrahydrocannabinol (THC) on body temperature, catecholamine synthesis and plasma corticosteroid levels were examined in the mouse at ambient temperatures of 31 degrees, 20 degrees and 10 degrees C in order to study the role of hypothermia in the THC's other actions. THC produced hypothermia at 10 degrees and 20 degrees C, but not at 31 degrees C. Dose related increases in dopamine and norepinephrine synthesis rates and plasma corticosterone levels were produced by THC at both 31 degrees and 20 degrees C. The effects of THC at 10 degrees C were biphasic. These data indicate that the effects of THC on brain catecholamines are not a result of drug induced hypothermia and may be a result of a direct action on neurons. PMID- 6247739 TI - Memory facilitation by naloxone is due to release of dopaminergic and beta adrenergic systems from tonic inhibition. AB - The post-training IP administration of naloxone (0.8 mg/kg) facilitates memory consolidation of the habituation of a rearing response to a tone in rats. Amphetamine (1.0 - 2.5 mg/kg or nicotine (0.2 - 0.5 mg/kg), and amphetamine (2.5 mg/kg) plus nicotine (0.5 mg/kg) have no effect. The higher doses of amphetamine or nicotine, however, when given together with a dose of naloxone which is ineffective alone (0.2 mg/kg), markedly enhance consolidation. Haloperidol (0.5 mg/kg), propranolol (0.5 mg/kg), and phenoxybenzamine (2.0 mg/kg) have no effect on their own; whereas tolazoline (2.0 mg/kg) impairs consolidation. The effect of naloxone (0.8 mg/kg) is antagonized by haloperidol and by propranolol, but not by phenoxybenzamine or tolazoline. The results suggest that naloxone causes memory facilitation through the release of central dopaminergic and beta-adrenergic mechanisms from a tonic inhibitory influence of endogenous opiate peptide systems. PMID- 6247740 TI - Nasopharyngeal angiofibromas: hazards of embolization. AB - A systematic approach to the diagnosis and treatment of angiofibromas is presented. The distinction between true and false internal carotid supply to these tumors as well as identification of vascular anatomical variants that may represent potential hazards of embolization are emphasized. Areterial supply to the cranial nerves, prevention of neurologic complications, and the use of inappropriate embolization materials are also discussed. PMID- 6247741 TI - Intraventricular metastases demonstrated by cranial computed tomography. AB - Intraventricular metastases from extracranial tumors are uncommon. Cranial computed tomography provides a uniquely noninvasive method to diagnose such metastases. However, enhanced intraventricular metastases may mimic normal enhancement of the choroid plexus. PMID- 6247742 TI - Evaluation and clinical significance of circulating immune complexes. PMID- 6247743 TI - Endogenous synthesis of prostaglandins E1 and I2 in 3T3 fibroblasts transformed by polyoma virus. Effects on adenosine 3':5'-monophosphate production. AB - Prostaglandins (PG)E1, E2 and I2 were produced by polyoma virus transformed (py) 3T3 fibroblasts. The levels of PGE1, PGE2 and 6-keto-PGF1 alpha (degradation product of PGI2) were 22.7, 225 and 33.2 ng/ml medium, respectively, 72 h after medium change. The stimulatory potencies of exogenous PGE1, PGE2 and PGI2 on adenosine 3':5'-monophosphate (cyclic AMP) formation were similar. Therefore, the prostaglandin mediated increase in cyclic AMP levels observed during growth of these cells (Claesson, H.-E., Lindgren, J.A. and Hammarstrom, S. (1977) Eur. J. Biochem. 74, 13) is largely (greater than 80%) mediated by PGE2 and to lesser extents by PGE1 and PGI2. PMID- 6247744 TI - Manipulation of platelet aggregation by prostaglandins and their fatty acid precursors: pharmacological basis for a therapeutic approach. AB - Addition of the one-, two- or three- series endoperoxide to human platelet-rich plasma tend to suppress aggregation, through the action of their respective non enzymatic breakdown products PGE1, PGD2, or PGD3 all of which elevate cyclic AMP levels. On the other hand, these stable primary products do not arise in appreciable amounts from intrinsic endoperoxides generated from either endogenous or exogenous free fatty acids. 5,8,11,14,17-Eicosapentaenoic acid (EPA) suppresses arachidonic acid (5,8,11,14-eicosatetraenoic acid) conversion by cyclooxygenase (as well as lipoxygenase) to aggregatory metabolites in platelets. Exogenously added EPA was capable of inhibiting PRP aggregation induced either by exogenous or endogenous (released by ADP or collagen) arachidonate. The hypothetical combination of an EPA-rich diet and a thromboxane synthetase inhibitor might abolish production of the pro-aggregatory species, thromboxane A2, and enhance formation of the anti-aggregatory metabolite, prostacyclin. Whereas EPA is not detectably metabolized by platelets, dihomo-gamma-linolenic acid (8,11,14-eicosatrienoic acid) is primarily converted by cyclooxygenase and thromboxane synthetase into the inactive metabolite, 12-hydroxyheptadecadienoic (HHD) acid. Pretreatment of human platelet suspensions with the thromboxane synthetase inhibitor imidazole unmasks the aggregatory property of PGH1 and DLL which was partially compromised by the PGE1 formed. The combination of the thromboxane synthetase inhibitor and an adenylate cyclase inhibitor unmasks a complete irreversible aggregation by DLL or PGH1. The basis of a dietary strategy that replaces AA with DLL must rely on the production by the platelet of an inactive metabolite (HHD) rather than thromboxane A2. PMID- 6247745 TI - Agonist-specific desensitization of PGI2-stimulated cyclic AMP accumulation by PGE1 in human foreskin fibroblasts. AB - Agonist-specific desensitization of prostaglandin I2-stimulated (PGI2)1 adenosine 3':5'-monophosphate (cyclic AMP) accumulation can be demonstrated in intact human foreskin fibroblasts (HFF) following a single exposure to PGE1 or a stable PGI2 analog (nitrilo-PGI2). A single PGI2-stimulation of HFF cells does not result in desensitization. Continuous re-addition of PGI2 over a 4 hr period does induce desensitization to subsequent PGI2-stimulation. HFF cells that are desensitized to PGI2 are also desensitized to PGE1 or nitrilo-PGI2 stimulation indicating that these agonists share a common adenylate cyclase complex. Desensitization to PGI2 can be measured after a 60 min, but not after a 30 min, exposure to PGE1 or nitrilo-PGI2. Once HFF cells are desensitized, a 12-24 hr period is required for the recovery of PGI2 sensitivity. The adenylate cyclase in membranes prepared from intact cells that were preincubated with PGE1 is also desensitized to subsequent PGI2-stimulation. Preincubation of cells with PGI2 does not induce desensitization of PGI2-stimulated adenylate cyclase. These data suggest that HFF cells must be constantly exposed to a biologically active prostaglandin for desensitization to occur. The intrinsic chemical lability of PGI2 may be a biochemical protection mechanism against desensitization in cells that normally respond to PGI2. PMID- 6247746 TI - Unique aspects of the modulation of human neutrophil function by 12-L-hydroperoxy 5,8,10,14-eicosatetraenoic acid. AB - 12-L-hydroperoxy-5,8,10,14-eicosatetraenoic acid (12-OOHETE), a labile intermediate generated by the lipoxygenation of arachidonic acid in platelets, and 12-L-hydroxy-5,8,10.14-eicosatetraenoic acid (12-OHETE), the reduction product of 12-OOHETE, were examined for their effects on human neutrophil function in vitro. 12-OOHETE elicited a maximal neutrophil chemotactic response at 4 microgram/ml, that exceeded by over 50% the maximal chemotactic response to 10-20 microgram/ml of 12-OHETE. Similarly 12-OOHETE was more potent than 12-OHETE in evoking neutrophil chemokinetic responses and in enhancing the expression of C3b receptors on neutrophils. The concentration of guanosine 3':5' cyclic monophosphate (cGMP) in neutrophils was increased to the same plateau level by 5 ng/ml of 12-OOHETE and by 50 ng/ml of 12-OHETE. Elevations in the concentration of cGMP were maintained for 30 min or longer by a single dose of 12-OOHETE, but fell between 10 and 20 min after the introduction of 12-OHETE. The release of neutrophil lysosomal enzymes by the chemotactic fragments of C5 was augmented substantially by 12-OOHETE, while 12-OHETE had only a marginal effect. The non chemotactic methyl ester of 12-OHETE failed to inhibit the chemotactic responses to 12-OOHETE at molar ratios that suppressed comparable response to 12-OHETE by 42-86%. Thus 12-OOHETE is more potent than 12-OHETE in the stimulation of some human neutrophil functions and in the elevation of the cellular concentration of cGMP. Furthermore, 12-OOHETE may activate neutrophils by pathways not available to 12-OHETE. PMID- 6247747 TI - Effects of prostaglandins on adrenal steroidogenesis in the rat. AB - To elucidate the role of prostaglandins in adrenal steroidogenesis, we studied aldosterone and corticosterone responses to 3 x 10(-8) M--3 x 10(-4) M of prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha), prostacyclin (PGI2), and arachidonic acid (AA) in collagenase dispersed rat adrenal capsular and decapsular cells. Whereas adrenocorticotrophic hormone (ACTH) and angiotensin II (AII) stimulated aldosterone production in capsular cells and ACTH stimulated corticosterone production in decapsular cells in a dose dependent fashion, aldosterone and corticosterone production were not stimulated significantly by PGE2, PGF2 alpha, PGI2, and AA. Although preincubation of dispersed adrenal cells with indomethacin (3 x 10(-5) M) markedly inhibited PGE2 synthesis, ACTH- and AII stimulated aldosterone production and ACTH-stimulated corticosterone production were not attenuated despite prostaglandin blockade. These results indicate that prostaglandins are unlikely to play an important role in adrenal steroidogenesis. PMID- 6247748 TI - In vitro effects of arachidonic acid and of inhibitors of its metabolism on the dog thyroid gland. AB - Incubation of dog thyroid tissue with arachidonic acid (10 to 200 microM) led to the following events: --low conversion to prostaglandins E2 and F2 alpha: 0.07% and 0.02% per hour and 100 mg tissue, respectively --inhibition of the stimulatory effect of low concentrations of TSH on thyroid secretion: the secretory effect of supra-maximal concentrations of TSH and of dB-cAMP was unaffected --inhibition of the cyclic AMP accumulation induced by TSH: this effect was inhibited neither by indomethacin nor by ETYA; cyclic AMP accumulation in response to cholera toxin or PGE1 was unaffected --no effect on cyclic GMP level --stimulation of thyroid proteins iodination. ETYA, but not indomethacin, depressed the iodination of thyroid proteins in resting and stimulated tissue. These data show that arachidonic acid-or a metabolite-can modulate thyroid responsiveness to TSH and suggest that lipoxygenase-products of arachidonic acid metabolism could be involved in thyroid proteins iodination. PMID- 6247749 TI - Specific receptors for prostaglandins in airways. AB - The relative bronchomotor activities of prostaglandins (PG) E1, E2, F2 alpha, F2 beta and I2 and of three synthetic E prostaglandin analogues (TR4161, TR4367 and TR4752) were determined on a large number of isolated preparations of guinea-pig trachea and human bronchial muscle. Each prostaglandin was capable of eliciting both contraction and relaxation, the relative incidence of these responses partly depending on concentration. TR4161 was a virtually pure relaxant; TR4367 was virtually devoid of bronchomotor activity; and TR4752 was a potent relaxant, devoid of contractant activity. The results also provided distinct rank orders of approximate potency for contraction and relaxation. Tachyphylaxis to the relaxant activities of PGE1 and TR4752 confirmed the underlying contractant activity of the two natural E prostaglandins. Antagonism with a high dose of indomethacin of the contractant actions of PGE1, PGE2 and PGF2 alpha confirmed the presence of relaxant activities in each. Inhaled aerosols of the same natural and synthetic prostaglandins were evaluated for irritant activity on the airways, using the cough response of the restrained conscious cat. All of them, except TR4161, elicited severe coughing. The rank order of potencies for irritancy differed from those for tracheobronchial contractant and relaxant activities. These findings suggest that the three responses studied arise from the activation of three distinct PG receptors in the airways. We propose the terms chi (contractant), psi (relaxant) and omega (irritant) for these putative receptors for prostaglandins or possibly other prostanoids. PMID- 6247750 TI - Prostaglandin induced shape changes in fibroblasts grown in cell culture. AB - PGE2 induced shape changes in porcine adventitial fibroblasts grown on glass in low density monolayer cell cultures. Incubation of the cells with PGE2 at concentrations of 100 ng/ml and 1000 ng/ml induced rounding of flat fibroblasts within one hours. The rounded cells had a small rim of cytoplasm around the nucleus and from one to several long thin arborizing cytoplasmic processes extending outward along the substratum. Removal of the PGE2 resulted in transient blebbing of the cell membrane of both the cell body and the processes as the cells returned to their flat normal morphology within one hour. The effect could be inhibited by 1% fetal calf serum. PGF2 alpha did not however induce similar changes. This difference between PGE2 and PGF2 alpha is similar to a report on spreading and migration of mouse peritoneal macrophages, and suggests that under certain conditions PGE2 may have the ability to induce shape changes in cells. PMID- 6247751 TI - [Evaluation of the left ventricular function by myocardial scintigram and radionuclide angiocardiography with technetium-99m pyrophosphate in patients with acute myocardial infarct (author's transl)]. AB - Myocardial scintigrams with 99mTc-pyrophosphate (PYP) were performed in 30 patients with acute myocardial infarct (AMI) and positive scintigrams were obtained in the 24 patients. In 12 patients the size of the AMI estimated from the scintigram with 99mTc-PYP was compared with the pulmonary capillary wedge pressure (PCWP). In the 7 patients with PCWP below 10 mmHg the mean area of the AMIs was 22 +/- 5.5 cm2 and that of in the 5 patients with PCWP beyond 10 mmHg was 41 +/- 12.4 cm2. This difference was statistically significant (p less than 0.05). In comparison with chest X-ray findings, the average size of the AMIs among 6 patients with alveolar and/or interstitial edema was 43 +/- 11.9 cm2 and that of among 8 patients without pulmonary edema was 25 +/- 9 cm2. The left ventricular ejection fraction (LVEF) was obtained by first pass method. In 12 patients LVEF and PCWP was compared. The 7 patients with PCWP below 10 mmHg did show significantly larger LVEF (49 +/- 8.2%) than that of 5 patients with PCWP beyond 10 mmHg (33 +/- 6.1%) (p less than 0.01). The mean LVEF in the 7 patients with pulmonary edema was 35 +/- 10.2% and that of in the 8 patients without pulmonary was 48 +/- 5.3%. Myocardial scintigram and radionuclide angiocardiography with 99mTc-PYP were useful for evaluation of the left ventricular function as well as detection of the AMI. PMID- 6247752 TI - [Disseminated intravascular coagulation and microangiopathic hemolytic anemia in muciparous adenocarcinoma of the stomach]. PMID- 6247753 TI - [Electromyographic changes in diabetic polyneuropathy]. PMID- 6247754 TI - [Value of dietary fiber in diabetes]. PMID- 6247755 TI - Endothoracic neurogenic neoplasm (analysis of 30 cases). PMID- 6247756 TI - [Fiessinger-Leroy-Reiter disease seen in a rheumatology unit. Apropos of 71 cases]. AB - 71 cases of Reiter's disease have been observed since 1972. After a study of the clinical characteristics of these cases, we report the results of 3 laboratory examinations which, grouped together, facilitate the diagnosis of the complete forms, but, above all, of the incomplete and synovial forms. The search for chlamydia cell inclusions was positive in 80% of cases where carried out. The lymphocyte transformation test with the chlamydia antigen was positive in 72% of cases. The search for HLA B27 was positive in 78% of cases. PMID- 6247757 TI - [Spinal nerve root complications of achondroplasia]. PMID- 6247759 TI - Changes in myoelectrical activity in the irritable colon syndrome with prolonged treatment. AB - Twenty patients with established irritable colon syndrome were studied at presentation and following a mean period of 14.3 months of bran treatment. An abnormal myoelectrical activity consisting of a high incidence of 3 c/m slow-wave electrical activity was recognised in the rectosigmoid and confirmed by objective automated frequency analysis. After the period of prolonged treatment, the high 3 c/m slow-wave activity persisted, but the incidence of 6--9 c/m activity increased. This was associated with an improved stool weight and transit time in patients with predominant constipation but no alteration in patients with predominant diarrhoea. PMID- 6247758 TI - Endocrine tumors of the pancreas. AB - A review of 33 patients operated on between 1951 and 1978 for endocrine tumors of the pancreas is presented. The series consists of 25 patients with hyperinsulinism, 6 with the Zollinger-Ellison syndrome, and 2 with the WDHA syndrome. Clinical features and diagnostic problems are discussed. A noticeable feature is that the average time lapse between onset of symptoms and final diagnosis in insulinoma patients has not been significantly reduced during the years covered by this review. This is in spite of the progress made in testing procedures and laboratory methods designed to diagnose hyperinsulinism. Resection of the tumor has been the preferred treatment in insulinoma patients, of whom 22 are still alive. Insulinomas were associated with other endocrinopathies in 3 cases. Patients with the Zollinger-Ellison syndrome had raised serum gastrin levels and increased basal acid output. Four patients are still alive. Two patients had other endocrinopathies. Both patients with the WDHA syndrome died shortly after the operation. One had biochemical evidence of multiple endocrinopathies. PMID- 6247760 TI - Side effects of substitution therapy--Newcastle 1976. PMID- 6247761 TI - Clinical neurological findings among car painters exposed to a mixture of organic solvents. AB - A full clinical neurological examination was used to study the possible effects of long-term exposure to low concentrations of mixtures of organic solvents on the nervous system. The exposed group consisted of 102 male car painters and the referents of 102 age- and sex-matched locomotive engineers and assistants. The psychoorganic syndrome, a decrease in the sense of light touch and pain, and an increase in the vibration threshold were more frequent among the car painters than among the referents, and the observed differences of these frequencies were statistically significant. The sense of vibration had been affected in the lower extremities of 65 of the 102 car painters and in 25 of the referents. Sensory functions seem to be the most vulnerable part of the nervous system of workers chronically exposed to different organic solvents. PMID- 6247762 TI - Efficient metal-ion catalyzed template-directed oligonucleotide synthesis. AB - The Pb2+ and Zn2+ ions are efficient catalysts for the polycytidylic acid directed polymerization of an activated guanylic acid derivative, guanosine 5' phosphorimidazolide. The products include oligomers of 30 to 40 units in length. The nucleotide residues are predominantly 2'-5' linked when Pb2+ is the catalyst, and predominantly 3'-5' linked in the presence of Zn2+. The significance of these results in the context of the prebiotic evolution of RNA polymerase is discussed. PMID- 6247763 TI - Beta-lipotropin: a new aldosterone-stimulating factor. AB - Beta-Lipotropin stimulated the production of aldosterone in collagenase-dispersed rat adrenal capsular cells. The maximum response obtained with beta-lipotropin was the same as the response obtained with corticotropin and was greater than that obtained with angiotensin II. These data suggest that beta-lipotropin may play a role in aldosterone regulation. PMID- 6247765 TI - Rat peritoneal mast cells: a model system for studying membrane fusion. AB - We used the mast cell as a model system for studying some of the membrane events which occur during exocytosis. Our observations indicate that the maximum cluster size of IgE molecules necessary for the "on" signal to activate a mast cell is 10 or less and that the "off" signal is not associated with the gross patching or pinocytosis of IgE and its Fc receptors. Furthermore, the use of Con A-Sepharose beads to stimulate mast cells has shown that such signaling is localized to the areas of stimulus, but this localization is not a function of desensitization over the rest of the cell since the subsequent addition of soluble Con A to locally released cells induced generalized degranulation. Ca2+ influx therefore acts in a localized manner to initiate degranulation. Following receptor cross linking, most of the membrane proteins and the layer of intervening cytoplasm are laterally displaced away from the areas of membrane interaction. This displacement may act as the signal for fusion to occur. The resulting fused bilayers are predominantly lipid, a situation which may be common in all transient membrane fusion. The mechanism of exposing histamine-containing granules to the extracellular space by blebbing is discussed. PMID- 6247764 TI - Synthesis and metabolism of prostaglandins, prostacyclin, and thromboxanes: the arachidonic acid cascade. PMID- 6247766 TI - The role of local design in membranes. AB - The IMP arrays are integral membrane multiprotein complexes that may be site specific control centers regulating the local concentration of specific ions by functioning as pumps, gates, or channels. In the case of the fusion rosette, an increase in Ca2+ may trigger local membrane fusion; in other cases, Ca2+ or H+ may be important physiological regulators. Ca2+ dependent regulatory proteins, such as calmodulin, and other parameters prevent widespread dispersion of the ions and permit fine local regulation. PMID- 6247767 TI - Collagenase: an experimental study of intervertebral disc dissolution. AB - This study reports the use of a purified form of the enzyme collagenase (Nucleolysin) to effect dissolution of the normal nucleus pulposus in a series of dogs and monkeys. A consistent dissolution effect has been observed. The toxicity of the enzyme to surrounding local tissues has been studied in the same species with an indication of safety in all areas other than intrathecal administration. A margin of safety in intrathecal administration between the effective dose and toxic dose has been suggested in the monkey. Mice LD50 studies and systemic toxicity studies in dogs show a satisfactory margin of safety for this enzyme. Guinea pig studies show no significant antigenicity. PMID- 6247768 TI - "Prespondylosis" and some pain syndromes following denervation supersensitivity. AB - Pain is determined by the neurologic properties of receptor organs, neurons, and their interconnections. These may become supersensitive or hyperreactive following denervation (Cannon's Law). A common cause of denervation in the peripheral nervous system is neuropathy or radiculopathy as a sequel to spondylosis. Spondylosis in its early stage may be "asymptomatic" or painless and hency unsuspected, because small-diameter pain fibers may not initially be involved despite the attenuation of the other component fibers of the nerve. The term "prespondylosis" is introduced here to describe this presently unrecognized phase of insidious attrition to the other functions of the nerve, especially the trophic aspect. It is postulated that many diverse pain syndromes of apparently unrelated causation may be attributed to abnormal noxious input into the central nervous system from supersensitive receptor organs (nociceptors) and hyperreactive control systems at internuncial pools. Furthermore, trauma to a healthy nerve is usually painless or only briefly painful, unless there is preexisting neuropathy. Some pain syndromes in muscle (eg, trigger points and myofascial pain syndromes) and nerve (eg, causalgia and diabetic neuropathy) that may be related to denervation are discussed. PMID- 6247769 TI - [Epidemiology of nosocomial clostridial myonecroses (gas gangrene)]. PMID- 6247770 TI - [Viruses and the pathogenesis of collagen disease (author's transl)]. PMID- 6247771 TI - [Clinico-etiological comparisons in chronic nonspecific lung diseases]. PMID- 6247772 TI - [Characteristics of cyclic nucleotide metabolism in the leukocytes of patients with bronchial asthma]. PMID- 6247773 TI - The association of spinal retroflexion with limb anomalies. AB - The spectrum of conditions in which retroflexion of the spine occurs includes anencephaly, iniencephaly, and Klippel-Feil syndrome. It was suggested by Gimour ('41) that a continuum may exist linking the latter two entities. The present paper attempts to reopen this question by reporting two specimens which have none of the above conditions, yet have spinal retroflexion and limb malformations. Combined with other isolated case reports, they show that spinal retroflexion can arise over a variable period of time. PMID- 6247774 TI - Changes in the mouse neuroepithelium associated with cadmium-induced neural tube defects. AB - The aim of this study was to investigate the teratogenic action of cadmium (Cd) on the developing mouse CNS. Pregnant mice were injected with 4 mg/kg CdCl2 on day 7, 8, 9, or 10 of gestation. These animals and saline injected controls were sacrificed either on the day before birth or at various times up to 48 hours after injection and the embryos examined grossly and histologically. Exencephaly occurred after Cd treatment on day 7 or 8 and its development was examined in day 8 embryos. Eight hours after Cd injection many cells of the closing neural plate contained dense-staining inclusions, thought to be autophagic vacuoles. After 24 hours this damage had almost disappeared, but the anterior neural folds, although looking histologically normal, were more open than in controls. Forty-eight hours after injection it was apparent that this part of the neural tube was not going to close and would result in exencephaly. Cd exposure on day 9 or 10 did not cause gross CNS defects such as exencephaly. On both days, twelve hours after Cd injection, similar dark-staining inclusions were seen in many cells throughout the CNS. After twenty-four hours there were variable amounts of cell death, resulting in some embryos in breakdown of parts of the wall of the neural tube. Forty-eight hours after treatment all inclusions and cellular debris had disappeared, indicating repair had taken place, but in some embryos, treated on day 9, severe lasting damage was seen as dorsal openings in the previously closed neural tube. PMID- 6247775 TI - Release of lamellar bodies from alveolar type 2 cells. AB - The release of lamellar bodies from rat alveolar type 2 cells has been studied during a 12hr dark/12hr light cycle. A proportion of the type 2 cell population was ultrastructurally abnormal. The cellular changes formed a spectrum raninging from mild to severe, culminating in rupture of the cell and release of its contents into the alveolar air space. The majority of aberrant cells were observed in animals killed during the dark period. A holocrine secretory mechanism is suggested for the release of lamellar bodies containing the surface active phospholipids of the alveolar lining. The release of lamellar material by a process of exocytosis was also observed, but only rarely, in spite of the numerous lamellar bodies seen in each cell cross-section. PMID- 6247776 TI - Actinoidin: a new inhibitor of ristocetin- and ristomycin-induced platelet agglutination. PMID- 6247778 TI - Cyclic AMP-independent inhibition of human platelet function by eicosapentaenoic acid. PMID- 6247777 TI - The effect of PGI2 and PGI2 analogues with increased stability on platelet cAMP content and aggregation. PMID- 6247779 TI - [Epstein-Barr-virus induced glomerulonephritis]. PMID- 6247780 TI - [Mecillinam]. PMID- 6247781 TI - Effects of islet-activating protein (IAP) on blood glucose and plasma insulin in healthy volunteers (phase 1 studies). AB - Islet-activating protein (IAP) is a new active substance purified from the culture medium of Bordetella pertussis. The active protein possesses a molecular weight of 77,000 and an isoelectric point of pH 7.8. The nature of IAP-action is characterized by enhancement of insulin secretory response to glucose and other stimulants. A single injection of IAP into spontaneous diabetes rats resulted in normalization of their glucose intolerance over a period of a month. Acute and chronic animal toxicity tests showed that LD50 of IAP was 127 micrograms/kg in mice and 144 micrograms/kg in rats. After these animal experiments, phase 1 studies were designed and undertaken to establish dosage, duration of action and other factors. IAP of 0.5 micrograms/kg or 1.0 micrograms/kg did not bring about any serious toxic or adverse effects in five volunteers. On the 4th day of a single injection of IAP, insulin secretory response was proved to be enhanced. Follow-up studies showed that the IAP-action continued over a month or at most two months. Two features of IAP, i.e., the enhancement of insulin secretory response and the long duration of the action, was confirmed in healthy persons as well as in animals. As expected, IAP has a strong antigenic reaction resulting in formation of IgG antibody and possibly IgE antibody. The antigenicity of IAP causes some hindrance to clinical usefulness. For avoidance of anaphylactic reaction, IAP should be given repeatedly with care. The problem concerning antigen-antibody reaction should be overcome as soon as possible before the clinical use of IAP as a medicament. PMID- 6247782 TI - Effects of long-term ozone exposure and dietary vitamin E in rats. AB - Rats fed on a vitamin E-deficient diet (E-depleted group) and a vitamin E supplemented diet (E-supplemented group) were exposed to 0.3 ppm ozone for three hours daily, five days a week for seven months. Then animals from each group were sacrificed, and electron microscopic studies on the lung and biochemical examinations on the lung and liver were performed. 1) Vitamin E concentration in serum decreased following ozone exposure in the E-supplemented group, whereas it remained unaffected the E-depleted group. 2) Both TAB value and % release of lysosomal enzyme (acid phosphatase) of the liver were increased in vitamin E depleted air-exposed rats, and showed even higher values following ozone exposure. Levels of both components were highest in the vitamin E-depleted ozone exposed rats, thus demonstrating that there are a marked increase in lipid peroxide and the increased labilization of lysosomes in this instance. 3) Arachidonic acid (20:4) of total lipid, phospholipid and lecithin in the lung tissue showed a tendency to decrease in vitamin E-depleted air-exposed rats. Those in the ozone-exposed animals showed in both groups a tendency to increase in total lipid and lecithin, and to decrease in phospholipid. However, a change in the fatty acid composition following ozone exposure was generally mild. 4) The fatty acid composition of phospholipid in lung washings did not show a remarkable change following ozone exposure in either group, thus suggesting that it has the resistivity to oxidation. 5) Morphological observations on the lung with the scanning and transmission electron microscopes did not reveal any clear differences between the two groups. The defensive effect of vitamin E on ozone toxicity induced by long-term exposure to ozone was not made clear by the morphological or biochemical examination of the lung. However, biochemical findings in liver of rats exposed to ozone suggested the possibility that vitamin E deficiency permits the damaging effects of lipid peroxidation on biological membranes. PMID- 6247783 TI - Effects of 2-nicotinamidethyl nitrate (SG-75), a new antianginal drug, on the cyclic AMP phosphodiesterase activity. AB - The effect of a potent coronary vasodilator, SG-75, on the purified cyclic AMP phosphodiesterase of the bovine heart was compared with that of papaverine. SG-75 inhibited the phosphodiesterase activity in a competitive manner, the IC50 being 10 mM. SG-75 was approximately 300 times less potent than papaverine in inhibiting the phosphodiesterase activity. Thus, it is unlikely that the phosphodiesterase inhibition by SG-75 is involved in its vasodilator action. PMID- 6247784 TI - The antibody-mediated and delayed type hypersensitivity response of mice exposed to polybrominated biphenyls. PMID- 6247785 TI - Residual effects of polybrominated biphenyls following perinatal exposure in rats. PMID- 6247786 TI - Distribution and excretion of 2,2',4,4',5,5'-hexabromobiphenyl in rats and man: pharmacokinetic model predictions. PMID- 6247787 TI - Cadmium toxicity and lipid peroxidation in isolated rat hepatocytes. PMID- 6247788 TI - Hepatic amoebiasis in immunodepressed mice. AB - The effects of immunodepression on intestinal amoebic lesions produced by Entamoeba histolytica were studied in inbred mice of the C3H/mg strain. Immunodepression was induced in two ways by giving (i) cyclophosphamide and (ii) anti-mouse lymphocyte serum. On immunodepression with the latter, although there was no difference in the degree of macroscopic intestinal damage, all five surviving immunodepressed mice showed hepatic lesions. It is noted that these had a striking histological resemblance to human and hamster lesions in hepatic amoebiasis. PMID- 6247789 TI - Probable occurrence of infections due to adenoviruses and parainfluenza 3 virus in residents of Khartoum Province in the Sudan. PMID- 6247790 TI - Acquisition of cytomegalovirus infection in infants following exchange transfusion: a prospective study. AB - A prospective study of newborn infants who required exchange transfusion was undertaken to evaluate the risk of transmission of cytomegalovirus (CMV). Buffy coat-, urine- and saliva-saturated throat swabs for viral cultures and serum specimens for CMV complement-fixing (CF) antibody were obtained from 45 infant mother pairs. Buffy coat from the donor blood was cultured and CMV CF titers measured. Viral studies were repeated on infants and mothers at six and 12 weeks after exchange transfusion. Fifteen infants received CMV seropositive blood and 14 infants received CMV seronegative blood. Sixteen infants who did not receive blood or blood products served as controls. Three of 12 antibody-positive newborns developed infection after getting seropositive blood. One of three antibody-negative newborns developed infection after getting seropositive blood. The presence of transplacental antibody does not appear to protect the infants. None of the control infants developed CMV infection. None of the infected infants were symptomatic. Although CMV infection in infancy can be acquired by routes other than blood, exchange transfusion with seropositive blood enhances the likelihood of acquiring infection. PMID- 6247791 TI - [Effect of surface-active agents on Na, K-ATPase from guinea pig kidneys]. AB - The effect of surface active agents on the activity of Na, K-ATPase and on the direct medium 18O exchange in the membrane preparations of the guinea pig kidney has been studied. The medium 18O exchange was considered as a character of the K+ dependent stage in ATPase reaction. Low concentration of all the surface active agents were shown to stimulate, and high concentrations -- to inhibit both ATPase and medium 18O exchange. The relation between medium 18O exchange and Na,K-ATPase activity was found to be equal to 1.5 +/- 0.1. The treatment of preparations by activating amounts of the surface active agents resulted in lowering this relation up to 1.0 +/- 0.09 and 1.3 +/- 0.04 for DOC and triton X-100, correspondently, due to a stronger stimulation of ATPase activity than of medium 18O exchange. With the inhibiting amounts of triton X-100 and histone H2a, this relation did not change, but it decreased in the presence of equal amounts of DOC. PMID- 6247792 TI - [Heterochromatinic segments in chromosomes of cultured human cells, sensitive and resistant to Coxsackie B viruses]. AB - Comparative karyological studies of C-heterochromatin have been made on line J-96 of human cells, which are susceptible to enteroviruses, and on cell line J-41 derived from this culture and possessing highly specific resistance to Coxsackie B viruses. It was shown that the development of specific resistance to Coxsackie B viruses was accompanied by the loss of one of the chromosomes of pairs 1 and 9, and by the dissapearance of two marker chromosomes. There appeared new marker chromosomes with additional C-heterochromatain regions. The data obtained are discussed with respect to a possible interrelationship between these chromosomal alterations and the specific resistance to Coxsakie B viruses. PMID- 6247793 TI - [Effect of vitamin D3 and carbostimulin on the content of carbohydrate metabolism substrates and the tricarboxylic acid cycle in liver of rats with experimental rachitis]. AB - The development of experimental rhachitis in rats is accompanied by a decrease in the dihydroxyacetonephosphate, glyceraldehyde-phosphate concentrations and by an increase in pyruvate, lactate, alpha-ketoglutarate, glutamate, oxalacetate and malate in the liver tissue. The feeding of vitamin D3 and carbostimulin normalizes, in the main, the concentrations of these metabolites. PMID- 6247794 TI - [Oxidative processes in carp liver mitochondria during adaptation to changes of CO2 concentration in water]. AB - Two-years-old carps (Cyprinus carpio L.) were kept for 1,3 and 7 days in the medium with different concentrations of CO2. In the fish liver mitochondria the rate of CO2 uptake (state 4p) and phosphorylation (state 3) as well as the value of the respiratory control and the activity of cytochrome oxidase and succinate dehydrogenase undergo significant changes. In fishes which were in the medium with 0.4 mM CO2 for a day the cytochrome oxidase activity in the mitochondria increases sharply, but that of succinate dehydrogenase decreases. The lowest activity of both enzymes is fixed in the carp liver mitochondria during the three day adaptation to such a medium. In the first day in the medium with 0.4 mM CO2 the rate of O2 uptake by the mitochondria in the states 4p and 3 rises. Seven days later the values of all the studied indices in the mitochondria reach gradually the control level. In the medium with 0.8 mM CO2 the oxidative processes in the mitochondria are more inhibited than in water with 0.4 mM CO2. PMID- 6247795 TI - [Peculiarities of phosphoric compound metabolism in liver mitochondria of carp adapted to higher concentrations of CO2 in water]. AB - The content of adenine nucleotides, ATPase activity, the amount of total and inorganic phosphorus in the carp liver mitochondria were studied as affected by CO2 high concentrations. It is shown that during adaptation to the CO2 higher level in the medium the amount of ATP in fishes undergoes the most significant changes. The organism response to the effect of carbon dioxide depends on its concentration in the medium and time of its action. When fishes were for 24h under conditions of the 0.4mM CO2 concentration, the ATP content in the carp liver mitochondria surpasses the control level and under conditions the 0.8 mM CO2 concentration it reaches the control level. The presence of 0.4 and 0.8 mM CO2 concentration decreases the ATP content 7 days later. The amount of inorganic phosphorus in the liver mitochondria of experimental fishes undergoes similar changes. An increase in the CO2 concentration in the water medium up to 0,4 and 0,8 mM inhibits Na+, K+, Mg2+-ATPase in fish organelles, the inhibition being more pronounced in a trial with 0.8 mM CO2. PMID- 6247796 TI - [Carbohydrate metabolism in sheep when adding carboxyline to their diet]. AB - The content of glycogen and glucose, as well as aldolase, phosphofructokinase, phosphoglucomutase, glucose-6-phosphatase and fructose-1,6-diphosphatase activities in liver tissue and the same activities in skeletal muscle of sheep were determined under the influence of prolonged addition of carboxyline separately and in combination with methionine, diammonium phosphate and potassium iodine to their diet. It is established that under the influence of carboxyline the glycogen content as well as aldolase and fructose-1,6-diphosphatase activities rise significantly in the liver of the tested animals. In the skeletal muscle only aldolase activity increases. PMID- 6247797 TI - [Dependence of creatine kinase and glycogen synthetase activities of skeletal muscles on state of adenine nucleotide phosphorylation and cAMP metabolism]. AB - Changes in the contents of adenine nucleotides, creatine phosphate, inorganic phosphate, creatine, glucose-6-phosphate and glycogen and the activity of adenylate cyclase, creatine kinase, glycogen phosphorylase 31:51-AMP phosphodiesterase and glycogen synthetase in muscles and of blood catecholamines were studied in adult rats before loading, immediately after the cessation of the muscular activity, and at rest. Adenine nucleotides are established to play a regulatory role in catabolic and anabolic processes nucleotides are established to play a regulatory role in catabolic and anabolic processes related to the muscular activity. It is established that compensation and supercompensation of the working losses of muscular creatine phosphate and glycogen are due to activation of anabolic processes under conditions of higher phosphorylation of the adenylic system. PMID- 6247798 TI - [Kinetic study of acid-soluble DNA formation under the effect of DNase I]. AB - A mathematical model of acid-soluble DNA formation under the effect of DNase I was developed. The data from the kinetic analysis suggest that at the stage of 10 60% solubilization the number of breaks in DNA single strands seem to be linearly dependent on the increment of acid-soluble DNA. This stage of acid-soluble DNA formation may be interpreted in terms of the monomolecular (pseudomonomolecular) reaction. PMID- 6247799 TI - [Epstein-Barr virus infection in early childhood]. PMID- 6247800 TI - [Treatment of constipation in patients in a nursing home with Vi-Siblin]. PMID- 6247801 TI - [Treatment of colon dyspepsia with Vi-Siblin]. PMID- 6247802 TI - [Herpes virus and cancer of the cervix]. PMID- 6247804 TI - [Malignant astrocytoma: evaluation]. PMID- 6247803 TI - [Pituitary adenomas. Surgical treatment by transphenoidal approach]. PMID- 6247805 TI - [Glomus tumors of the orbit]. PMID- 6247806 TI - [State of the transmission capacity and the differential sensitivity of the auditory system in the sequelae of craniocerebral injury]. PMID- 6247807 TI - [Evaluation of the adequacy of general electroanesthesia based on data from studies of the hormonal profile of patients during surgery]. PMID- 6247808 TI - [Copper metabolic disorder in extravasal stenosis of the celiac trunk]. AB - Copper metabolism was studied in 82 patients with extravasal stenosis of the celiac trunk and in 14 patients with disturbed potency of the celiac trunk and inesenterial arteries of atherosclerotic etiology. The following parameters were analyzed: activity of ceruloplasmin and cytochromoxidase and copper content in the blood serum, copper and cytochromoxidase in the liver. It has been established that the level of the above elements in the blood and liver can be a diagnostic sign of chronic ischemia of the liver in patients with extravasal stenosis of the celiac trunk. PMID- 6247809 TI - Recovery and in vitro cultivation of a coronavirus from laboratory-induced cases of feline infectious peritonitis (FIP). PMID- 6247810 TI - Amforol--effective treatment for enteritis in dogs. PMID- 6247811 TI - Why I recommend vaccinating cattle against bovine virus diarrhea (BVD). PMID- 6247812 TI - [Pituitary dwarfism in a German shepherd dog (author's transl)]. AB - Pituitary dwarfism has been described in more than 20 German shepherd dogs. Some cases probably were caused by persistent cysts of Rathke's pouch. This is the first histopathological, immunohistochemical and endocrinological study. A 13 month-old, 7-kg, dwarf purebred German shepherd bitch with alopecia and hyperpigmentation was admitted to the clinic for euthanasia. Retardation of growth was noticed when the dog was about two months old. No littermates had this condition. Two subsequent breedings from the same parents produced normal offspring. The clinical parameters in our dog (hematology, function of liver and kidney) were normal. Grossly, the pituitary gland had small and large multiple cysts, which light microscopy showed to be exclusively within the adenohypophysis. The latter had pressure atrophy, and immunohistochemically showed only remnants of the hormone-producing cells (growth hormone-GH; prolactin PRL; thyrotropin-TSH; luteinizing hormone-LH; adrenocorticotrophin-ACTH/MSH). The thyroid was relatively small, and histologically showed focally resting follicles without lumen. Endocrinological studies showed a surprisingly high value for serum growth hormone (cGH 4.1 ng/ml; normal range 1.8-3.8 ng/ml as determined by a specific homologous radioimmunoassay) and a pathologically low serum somatomedin (SM 0.132; normal value more than 0.50 unit/ml, determined by 35S incorporation in piglet rib cartilage). Hypothyroidism was verified by a low T4 binding value (T4 0.9 micrograms/100 ml; normal 4.1 +/- 0.9 micrograms/100 ml) and a low thyroid binding index (TBI 0.54; normal 0.61 +/- 0.05). While ACTH was lowered (ACTH less than 10 pg/ml; normal 74-210 pg/ml), cortisol was normal (0.81 micrograms/100 ml; normal 0.5-2.5 micrograms/100 ml). Pituitary dwarfism in the 13-month-old bitch can be ascribed to the persistence of one end of the ductus craniopharyngeus, Rathke's pouch. Pressure atrophy of the adenohypophysis led to the loss of most of the hormone-producing tissue. An increase in growth hormone with lowered somatomedin raises questions. We have no conclusive explanation for this, due to the present lack of knowledge of how growth is regulated. High growth hormone and low somatomedin values are found in Laron's syndrome in infants. The literature indicates that pituitary dwarfism in German shepherd dogs may be a hereditary autosomal recessive trait. PMID- 6247813 TI - Porcine fetuses with pulmonary hypoplasia resulting from experimental swine influenza virus infection. AB - Porcine fetuses between 51 and 57 days of gestation were inoculated intraallantoically with swine influenza virus and examined 3, 7, 13, 28 and 58 days after inoculation. At 3 and 7 days, severe epithelial necrosis was seen in most bronchial buds and there was moderate epithelial necrosis in more fully differentiated major bronchi. As a result of the epithelial injury, bronchial buds did not develop further and the surrounding mesoderm failed to differentiate. By 28 days, the lungs of inoculated fetuses were about one-half the size of the normal control lungs. Microscopically, the lungs of the inoculated fetuses were composed of major bronchi surrounded by multiple islands of cartilage, medium to large arteries and a few small, incompletely developed lobules. Influenza virus was isolated most consistently and in greatest quantity from the lung, trachea and chorion of inoculated fetuses. Influenza viral antigen was shown in the epithelium of bronchial buds, bronchi and the trachea by direct fluorescent antibody staining. Hemagglutination inhibiting antibodies to influenza virus were first found in the serum of an inoculated fetus at 13 days and in the sera of all inoculated fetuses at 28 and 58 days. PMID- 6247814 TI - Spontaneous intraductal mammary carcinoma in a rhesus monkey. PMID- 6247815 TI - Sex cord stromal tumor of the cat: so-called androblastoma with Sertoli-Leydig cell pattern. PMID- 6247816 TI - Malignant fibrous histiocytoma involving the ilium in a cat. PMID- 6247817 TI - Channel catfish virus: physicochemical properties of the viral genome and identification of viral polypeptides. PMID- 6247818 TI - Physical and genetic analysis of the herpes simplex virus DNA polymerase locus. PMID- 6247819 TI - Initiation factor preparations from poliovirus-infected cells restrict translation in reticulocyte lysates. PMID- 6247820 TI - Detection of virus-specific antigens in EB-(P3HR1) virus-superinfected Raji cells by immunoprecipitation. PMID- 6247821 TI - A quantitative in vitro focus assay for bovine papilloma virus. PMID- 6247822 TI - Vesicular stomatitis virus and sindbis virus glycoprotein transport to the cell surface is inhibited by ionophores. PMID- 6247823 TI - Identification and characterization of dimeric and trimeric circular forms of avian sarcoma virus-specific DNA. PMID- 6247824 TI - Characterization of the endogenous feline leukemia virus-related DNA sequences in cats and attempts to identify exogenous viral sequences in tissues of virus negative leukemic animals. PMID- 6247825 TI - Alkaline deoxyribonuclease induced by herpes simplex virus type 1: composition and properties of the purified enzyme. PMID- 6247826 TI - Inhibition of respiratory syncytial virus by bis(5-amidino-2 benzimidazolyl)methane. PMID- 6247827 TI - Polyoma virus adsorbs to specific sialyloligosaccharide receptors on erythrocytes. PMID- 6247828 TI - Heterogeneous population of virus DNA in serially passaged Marek's disease virus preparation. PMID- 6247829 TI - Mapping of the 3' terminus of the large late ad-2 transcript by electron microscopy. PMID- 6247830 TI - [The effect of glucagon on plasma adenosine cyclic-3'-5'-monophosphate in intrahepatic and extrahepatic cholestases]. PMID- 6247831 TI - [Pyrophosphate heart scan in the diagnosis of various forms of angina pectoris]. PMID- 6247832 TI - [Role of kymographic pertubation and radioisotopic studies in the diagnosis and evaluation of the effectiveness of sulfide bath treatment in tubal sterility]. PMID- 6247833 TI - [Blood kinin system state in sepsis in newborn infants]. PMID- 6247834 TI - [Functional state changes in the hypophyseal-adrenal system in bronchial asthma in children receiving specific treatment]. PMID- 6247835 TI - [Skeletal x-ray studies in tubular bone pathology in children]. PMID- 6247836 TI - [Paramagnetic diethyleneimides of urethane phosphoric acids as antitumor agents]. AB - Under study were paramagnetic diethylene imides of urethan phosphoric acids containing three type groups showing carcinostatic activity. There was found small toxicity and a wide spectrum of the antitumor effect of the compounds, also the correlation between the chemical structure and carcinostatic effect was investigated. The nitroxyl radical was shown to participate in the antitumor effect manifestation. PMID- 6247837 TI - [Lymphoscanning potentials in the diagnosis of lung cancer metastasis]. AB - Clinical estimation is given of indirect isotope lymphoscanning, performed by intrapulmonary administration of Au-198, for diagnosing lung cancer metastases. The method enables obtaining scannographs of intrathoracic lymphnodes and also, based on the changes in scannograms, judging the presence of lymphogenic metastases. Lymphoscanning is a technically feasible and safe method, it provides comparatively large information for diagnostic purposes and may occupy an important place among other diagnostic technics for ascertaining the extent of lung cancer proliferation. PMID- 6247838 TI - [Surgical treatment of malignant liver tumors]. AB - One hundred and nineteen patients were operated upon, 89--for primary cancer of the liver, 30--for cancer metastases. Radical operations for primary cancer of the liver were performed in 5 of 89 patients, and in 8 of 30 patients with metastatic involvement of the liver. In radical operations for malignant hepatic neoplasms frequently there would arise the necessity of a temporary exclusion of the organ from the portal and caval circulation. PMID- 6247839 TI - [Isolation of acellular tumor filtrate (ATF) from tumor tissue]. PMID- 6247840 TI - [Etiology of rheumatism and of nonrheumatic myocarditis]. PMID- 6247841 TI - [Prognostic importance of determining the nonspecific resistance and allergy indices in erysipelas]. PMID- 6247842 TI - [Molecular biologic characteristics of vesicular stomatitis virus]. PMID- 6247843 TI - [Cellular immune response detected in blast transformation test with lymphocytes from rabbits immunized with nucleocapsid of herpes simplex type 2 virus]. AB - A preparation of herpes simplex virus type 2 (HSV-2) nucleocapsid (NC) was obtained after treatment of intracellular virus with detergents followed by centrifugation in linear sucrose density gradient. Electron microscopic analysis revealed polymorphism of HSV-2 NC population. Three main types of capsid structures were found: empty capsids, NC containing various amounts of nucleoid material, and NC with complete nucleoid. Morphological heterogeneity correlated with heterogenous sedimentation profile of the total NC preparation of labeled virus represented by light, intermediate, and heavy structures. Specific blasttranformation tests with lymphocytes from rabbits immunized with HSV-2 NC demonstrated differences in the primary and secondary cellular immune responses. The secondary cellular immune response was characterized by a more rapid and strong increase in BTT values than the primary immune response. PMID- 6247844 TI - [Role of Powassan virus in the etiological structure of tick-borne encephalitis in the Primorsky Kray]. AB - Composite studies conducted annually in the Primorsky kray showed the tick-borne encephalitis virus to play the main etiological role in the group of encephalites with the spring-summer incidence. In 1976--1978, virological studies of 69 cases of the disease yielded 11 strains of tick-borne encephalitis virus. In 1978, from the blood of clinically normal woman after a tick bite strain 555 was first isolated which was identified as Powassan virus, and antigenemia was observed for 53 days using the fluorescent antibody technique. In the same period, serological examinations of the blood sera from 117 patients demonstrated antibody to tick borne encephalitis virus in 69.2%, to Powassan virus in 4,3% and to both viruses simultaneously in 4.3%. Besides, antibody to tick-borne encephalitis virus, Powassan virus and both viruses simultaneously was found in patients with progredient forms of tick-borne encephalitis and in subjects with the history of tick attachment. PMID- 6247845 TI - [Enterovirus type 71 pathogenicity for laboratory animals]. AB - Enterovirus type 71 (E71) strains isolated from specimens of the brain and feces of children during an outbreak of poliomyelitis-like infection in Bulgaria in 1975 produce paralytic disease in newborn and adult cotton rats, newborn white mice, and monkeys. By the type of the myo- and neurotropic properties manifested in animal experiments the Bulgarian E71 strains are very close to neuropathogenic strains of Coxsackie A7, A14, and A16 viruses. The infection induced by the Bulgarian E71 strains in green monkeys was by clinical symptoms (tremor, convulsions, death), the speed of the development of the process and the type of morphological lesions particularly similar to the clinical and morphological manifestations of infection observed in most severe cases in children during the outbreak in Bulgaria. Inoculation of newborn and adult cotton rats, newborn white mice and Macaca rhesus monkeys with large doses of the prototype BrCr strain of enterovirus 71 (10(5.0)--10(6) TCD50) caused no clinically manifest disease of the animals. PMID- 6247846 TI - [Epidemiological studies of rubella and cytomegalovirus infection in the North of the USSR]. AB - Seroepidemiological characteristics of rubella and cytomegalovirus infection in the north of the USSR were studied. Examinations of 21,000 patients with rubella and serological survey of 1500 subjects revealed the identity of the main epidemiological indices and age changes in antibody to rubella virus in the northern and central parts of the USSR. The general percentage of seropositives to cytomegalovirus is significantly higher in the north than in other parts of the country. The importance of the observed findings for the determination of the incidence of congenital pathology due to rubella and cytomegalovirus infection in the north is discussed. PMID- 6247847 TI - [On the role of virus infection in the pathogenesis of vulvovaginitis in young girls]. AB - The antigens of a number of widely prevalent viruses and changes typical of the cytopathic effect of these viruses were found in the epithelial cells of vaginal secretes in 44 out of 49 examined young girls with protracted forms of vulvovaginite. Mixed virus infection of the vaginal mucosa was diagnosed in 22 girls. More frequently than others, parainfluenza (57.1%) and adenovirus (59.2%) infections were detected in the patients. In girls of the control group, parainfluenza infection was diagnosed in 5.9% and adenovirus infection in 32.3%. Antigens of Coxsackie A and B (16.3%), influenza A2 and B (6.1%) and respiratory syncytial (6.1%) viruses were found in the vaginal mucosa in patients with vulvovaginitis only. A possible role of virus infection in the pathogenesis of vulvovaginitis in childhood is discussed. PMID- 6247848 TI - [The course of flavivirus infections in mice in the presence of the graft versus host reaction under conditions of 2-way incompatibility]. AB - The graft versus host reaction (GVHR) under conditions of two-way incompatibility was shown to increase average longevity (AL) of mice with experimental tick-borne encephalitis (TBE) and to activate asymptomatic infection caused by Langat virus. Experiments with TBE virus demonstrated participation of viable T lymphocytes in GVHR. Inhibition of function of both humoral and cellular immunity was shown to occur in GVHR. The assumption that the increase in the average longevity in TBE is associated with the inhibition of the damaging function of cellular immunity is experimentally substantiated. PMID- 6247849 TI - [Radioimmunoassay for the detection of hepatitis type A virus]. AB - A solid phase radioimmunoassay variant for type A hepatitis virus detection is presented. The specificity of the method was demonstrated in the competitive neutralization tests. PMID- 6247850 TI - [Restoration of the sensitivity of cells resistant to Coxsackie B3 virus after treatment with sensitive cell filtrate]. AB - The study was done with J-96 cell line sensitive to Coxsackie B3 virus and the subline J-41 derived from it and resistant to this virus. In order to determine the substrates responsible for the susceptibility or resistance of these cells to Coxsackie B3 virus, homogenates and filtrates of the susceptible cells were inoculated into resistant ones and vice versa. Inoculation of the resistant cell homogenates into the susceptible cells at various intervals after virus inoculation did not inhibit virus development. Inoculation of a filtrate of the susceptible cells into resistant ones followed by long-term cultivation resulted in restoration of the susceptibility. Reversion of susceptibility to Coxsackie B3 virus was gradual and accompanied by restoration in the cells of positive Homari test to alkaline phosphatase. The positive result was obtained twice in the absence of reversion in control cells not treated with the filtrate. PMID- 6247852 TI - [The value of coloscopy in modern diagnosis and therapy of colonic diseases]. PMID- 6247853 TI - Progress in the treatment of malignant tumors of childhood--introduction. PMID- 6247851 TI - Multiple endocrine neoplasia syndromes. AB - The multiple endocrine neoplasia (MEN) syndromes consist of three distinct disease entities. They have in common adenomatous, carcinomatous or hyperplastic involvement of a variety of endocrine glands, and an autosomal dominant inheritance. MEN I includes hyperparathyroidism, islet cell and pituitary tumors. The components of MEN IIa are hyperparathyroidism, medullary thyroid carcinoma and pheochromocytoma. MEN IIb includes multiple neuromas, medullary thyroid carcinoma and pheochromocytoma. Effective tests are available for the early detection of components of the syndromes in potentially affected patients. Screening can lead to therapeutic intervention before clinical sequelae ensue. PMID- 6247854 TI - Treatment of Wilms' tumor in children. PMID- 6247855 TI - Malignant liver tumors in infants and children. PMID- 6247856 TI - The stereoselective enzymic reduction of the synthetic 9-ketocannabinoid, nabilone, in vivo, in isolated liver cells and in liver homogenate. AB - 1. The enzymic reduction of the two optical isomers of nabilone, 6aR, 10aR and 6aS, 10aS, has been studied separately in the rat, in isolated hepatocytes, and in the 9000 g supernatant fraction of rat liver homogenate. The SS-nabilone was the more active substrate in all three cases. 2. In all three systems, the only carbinol formed from SS-nabilone was the S-(equatorial)-carbinol. In contrast, the reduction of RR-nabilone gave only S-(axial)-carbinol in the intact rat and in the isolated hepatocyte, but gave in the liver homogenate fraction a mixture of S-(axial)-carbinol and R-(equatorial)-carbinol. 3. The results show that the reduction of nabilone in vivo in the rat proceeds with rigid stereochemical control and that only the S-carbinols are formed. 4. The results also suggest that observations made with the intact liver cell may be more predictive of events in vivo than are those made with broken cell preparations. PMID- 6247857 TI - [The significance of dietary fat and fiber for the aetiology of colon cancer (author's transl)]. AB - Dietary habits of 49 patients with colorectal carcinoma or precancerous adematous polyps were investigated and compared with age- and sex matched, healthy controls. The dietary fiber intake of the tumor group was not significantly lower than control. Tumour patients were found to eat more animal fat than controls, the difference not reaching statistical significance. By contrast, we found a highly significant difference in the ratio of daily dietary fat/fiber intake (p less than 0.001). The ratio was 19.1 +/- 1.1 in tumour patients and 14.5 +/- 0.6 in controls. It is concluded that in the genesis of colorectal carcinoma, the relation of dietary fat to fiber might be more important than the intake of these two dietary constituents in absolute terms. PMID- 6247858 TI - Paramagnetic species in beta-thalassemic sera: an ESR study. AB - Homozygous beta thalassemic sera show an electron spin resonance (ESR) signal at g approximately equal to 6 which is not present in normal and heterozygous sera. The signal arises from high spin heme groups exhibiting a departure from tetragonal symmetry toward rhombic. Binding by a serum protein is very likely responsible for such a distortion. In contrast with other authors' findings, we report that heme-human albumin complex shows a similar rhombic distortion. The observed ESR signal at g approximately equal to 6 is then attributed to this complex. PMID- 6247859 TI - A study of the substrate and inhibitor specificities of AMP aminohydrolase, 5' nucleotidase, and adenylate kinase with adenosine carboxylates of variable chain length. AB - A series of AMP analogs in which a terminal carboxylate residue, linked to C 4' of the ribose moiety of adenosine by zero, one, or two methylene groups (1,2,3) or by the unsaturated ethylidene link (4) replaces the phosphate anion, is tested for activity as substrates or effectors of three enzymes known to interact with AMP with a different degree of specificity. 2-4 are substrates of AMP aminohydrolase, 3 and 4 are competitive inhibitors of adenylate kinase, and all acids produce competitive inhibition of the least specific enzyme, 5' nucleotidase. These activities can be correlated with the intramolecular flexibility of anionic substituent and adenine base which in turn is expressed in typical shifts of the proton magnetic resonance signal of purine H-8. The uronic acid 1, having a rigid molecular conformation, is inactive towards two AMP dependent enzymes and little active with the third, indicating that this type of compound is not suitable as a nucleotide antagonist whereas nucleoside carboxylates of type 2 and 3 have a higher potential as effectors of nucleotide metabolism. PMID- 6247860 TI - Culture density and age-dependent interactions of 3T3 AND SV3T3 cells with immobilized and soluble Lens culinaris lectin. AB - Short term binding of both Balb/c derived 3T3 cells and SV3T3 cells to 2B Sepharose coated with Lens culinaris lectin (LCL) was compared with their LCL induced agglutinability in relation to culture density and age. The cells were grown for 4 days either to low (LD) or to high density (HD); for certain experiments HD-cells were stimulated (HDS) by a short trypsin treatment and/or by addition of fresh medium. HD-3T3 cells bound somewhat faster to immobilized LCL than LD-3T3 cells, although LD-3T3 cells agglutinated at lower LCL concentrations. In the case of SV 3T3 cells, binding was much less pronounced for HD than for LD cells. The agglutinability of HD-SV 3T3 cells, however, was greater than that of the other transformed groups. Upon stimulation, binding and agglutinability data of both HD cell lines began to resemble the results obtained with LD-cells. Taken together, the date revealed in all cases an inverse relationship between binding and agglutinability, i.e., high agglutinability was closely correlated with slower binding and vice versa. The results indicate that culture density and age-dependent differences in cell surface architecture can be detected by short term binding to immobilized LCL. PMID- 6247861 TI - [Juvenile angiofibroma of the ethmoidal labyrinth in a young woman]. PMID- 6247862 TI - [Mixed tumor of the root of the tongue]. PMID- 6247863 TI - The influence of the hind gut microflora on the digestibility of protein and amino acids in growing pigs elucidated by addition of antibiotics to different fractions of barley. PMID- 6247864 TI - [Glycogen content and activities of phosphorylase and glucose-6-phosphatase in the fast and slow muscles of representatives of different classes of vertebrates]. AB - Studies have been made on glycogen content as well as on the activity of phosphorylase and glucose-6-phosphatase in fast and slow muscles from representatives of 6 classes of vertebrates (Lampetra fluviatilis, Cyprinus carpio, Rana temporaria, Rana ridibunda, Emys orbicularis, hen, rat). Glycogen level and glucose-6-phosphatase activity are either higher in slow muscles, or practically identical in both types of muscles (glucose-6-phosphatase is absent from the fast muscles of hens and rats). On the contrary, phosphorylase activity is higher in fast muscles, this finding being true only for higher vertebrates and lampreys. PMID- 6247866 TI - [Physiological features of the wing muscle fibers of Locusta migratoria locusts]. AB - In bifunctional dorsoventral muscle M-120 of the locust Locusta migratoria migratorioides three groups of fibers have been found which differ with respect to their electrophysiological properties. The evoked fast potentials in the fibers of caudal portion differed from fast potentials observed in the fibers of rostral and intermediate portions of the muscle. In the fibers of the caudal and intermediate portions of muscle, not only fast, but other depolarization potentials were also recorded which differ in the amplitude and duration, as well as the inhibitory postsynaptic potentials. It was shown that fibers in these three parts of the muscle differ in their voltage-current properties. It is concluded that different types of potentials are due to peculiarities of innervation and to structural heterogeneity of muscle fibers. PMID- 6247865 TI - [Cytochemical demonstration of cyclic nucleotide phosphodiesterases in the taste buds of Testudo horsefieldi turtles upon exposure to flavored substances]. AB - Phosphodiesterase of cyclic nucleotides was found cytochemically on the plasmat membrane of the apical part and microvillar projections of the receptor cells and, to a lower extent on the membranes of microvilli of the supporting cells as well as on the mucose granules of the taste buds of the tortoise Testudo horsfieldi. Administration of 1/250 M quinine chloride to the surface of the tongue results in the disappearance of the products of the enzymic reaction from the surface of the mentioned membranes. After application of 0.25 M surcrose, the reaction products are found within the apical part of the receptor cells on the membranes of the plain endoplasmic reticulum. Possible role of cyclic nucleotides in taste reception is discussed. PMID- 6247867 TI - [Effect of ginseng preparations on the activity of identified neurons of Heliz lucorum snails]. AB - It has been demonstrated that the effects of aqueous extracts from the native ginseng and extracts of genseng tissue culture on the activity of identified neurones are identical. Neuronal excitability, tested intracellularly, significantly increases to the 60th minute of drug application, whereas gradually developing depolarization simultaneously disappears. Rhythmic orthodromic stimulation revealed the increase in neuronal responses during ginseng perfusion, the synaptic efficiency remaining constant. It is suggested that changes in transmembrane potential level evoked by administration of ginseng preparations are not related to changes in the excitability. Changes in the adaptive capacities of the neurones in invertebrate animals are due to nonspecific endoneuronal shifts in cellular metabolism induced by ginseng administation. PMID- 6247868 TI - The effect of glucagon and prostaglandin E1 on cyclic AMP levels in liver of heat exposed hamsters. AB - Cyclic AMP levels in liver slices of hamsters exposed to 35 degrees C for 21 days and controls maintained at 22 degrees C was found to be similar in basal conditions. Glucagon (10 microgram/ml) caused 3.5 times elevation of cyclic AMP levels in control hamsters and 9 times elevation in 35 degrees C exposed hamsters, thus a difference of 150% of the nucleotide concentration was found between the two experimental groups. When 10(-2)M theophylline was added, the cyclic AMP levels were 80% higher in 35 degrees C exposed hamsters both in the presence and absence of 10 microgram/ml glucagon. The difference between controls and heat exposed animals was found to be the same when various concentrations of both glucagon or prostaglandin E1 were added to the liver slices. Adenylate cyclase activity was similar in both experimental groups, while low Km phosphodiesterase was significantly less active in the liver of 35 degrees C exposed animals when compared to the controls. PMID- 6247869 TI - Plasma 11-deoxycortisol, androstenedione, testosterone and ACTH in comparison with the urinary excretion of tetrahydro-11-deoxycortisol as indices of the pituitary-adrenal response to oral metyrapone. AB - Plasma levels of ACTH, 11-deoxycortisol, androstenedione and testosterone and urinary tetrahydro-11-deoxycortisol were determined during a two day oral metyrapone test using doses of 1.5 g every 6 h. The level of 11-deosycortisol 48 h after the start was distinctive regarding the assessment of pituitary ACTH secretory capacity. The rise of androstenedione concentration after 48 h is distinctive in a similar way, whereas ACTH determination is of little diagnostic value in this respect. Further, an increase in testosterone level can be observed in cases of low basal testosterone production. This increase is probably the result of peripheral conversion of androstenedione to testosterone. Where the basal testosterone concentration was high, no change could be measured. PMID- 6247871 TI - Changes in the biomechanical properties of skin and aorta induced by corticotrophin treatment. AB - The work presented here is an investigation of the effect of elevated levels of corticosteroids on the biophysical properties of skin, aorta and muscle tendon. Rats were given corticotrophin injections for 10, 30 and 60 days to elevate the level of plasma endogenous corticosteroids. The corticotrophin treatments did not change the water or collagen content of specimens from dorsal skin, thoracic aorta and peroneal muscle tendons, tested mechanically. Changes became evident after longer treatment times. For both skin and aorta, the tensile strength, elastic stiffness and failure energy were increased after 60 days of treatment. The corticotrophin treatment did not influence the mechanical properties of muscle tendons. Complete reversibility of changes in the mechanical properties induced by 30 days of corticotrophin treatment was found after an additional period of 30 days of saline injections. This study indicates that an increased level of plasma corticosteroids elicited by corticotrophin treatment may increase the stiffness of the connective tissue of the organism. In the aorta this results in loss of capacitive function with increased haemodynamic strain on the aortic wall. PMID- 6247870 TI - The development of the pituitary-adrenal axis in the guinea pig. AB - The concentration of cortisol and ACTH in the umbilical vein plasma of the foetal guinea pig has been measured over the later half of gestation. Between 55--60 days there is a large increase in the concentration of both. Injection of ACTH1 24 into the foetal guinea pig elicits a relatively small increase in plasma cortisol at 46--55 days, a somewhat greater response at 56--60 days and a large response at 61--66 days. Between 47--55 days and 58--63 days cells prepared from the foetal adrenal show a large increase in their responsiveness to ACTH stimulation as measured by cortisol and androstenedione output. However, there was no clear difference in responsiveness between 58--60 days and 61--63 days. Thus between 56--60 days the foetal adrenal appears less responsive to ACTH stimulation in vivo than in vitro. ACTH in the circulation of the guinea pig is present in high-molecular-weight and low-molecular-weight forms and the ratio of concentration of ACTH1-39 to that of the high-molecular-weight forms rises after 60 days. It is proposed that this is an important factor in inducing an increased steroid response from the foetal adrenal. PMID- 6247872 TI - Effects of propranolol and atenolol on plasma and urinary cyclic adenosine 3',5' monophosphate in hyperthyroid patients. PMID- 6247873 TI - Human thyroid stimulating activity and clinical state in antithyroid treatment of juvenile Graves' disease. PMID- 6247874 TI - Binding of thyrotrophin to low molecular weight fragments of human thyroid membranes. AB - The LATS absorbing activity from thyroid homogenates which is associated with the soluble thyroid fraction (4S-LAA) binds TSH in addition to LATS. This may indicate that 4S-LAA originates from the receptor sites for TSH at the thyroid cell surface. The affinity of 4S-LAA for TSH is much lower than that of thyroid membranes suggesting that 4S-LAA represents incomplete receptor sites or receptor sites which are altered in their structure. PMID- 6247875 TI - [Contribution to the study of stress (author's transl)]. AB - The research activity of the physiological laboratories (Medical and Hygienic Institute, Cluj-Napoca, Roumania) in the area of stress studies is described from three aspects: a) Methods of stress provocation and assessment; b) The effects of hormones, especially of anterior pituitary, on the adaptation to physical load; c) Nervous and endocrine factors of stress (physical exertion, fatigue, high pressure, anoxia). PMID- 6247876 TI - Blood lymphocyte subpopulations show characteristic changes during ACTH therapy in acute exacerbations of multiple sclerosis. AB - The percentages of the various lymphocyte subpopulations in blood samples of 22 patients suffering from acute bouts of multiple sclerosis (MS) were determined by E rosette formation and peroxidase staining techniques, respectively, before and during ACTH therapy. In accordance with earlier reports, most of the subjects showed a normal increase of their plasma cortisol concentrations in an ACTH quick test, which was routinely performed before the beginning of therapy. We observed a significant transitory decrease of the absolute and relative T-cell proportions with a minimum around the tenth day of treatment, accompanied by inverse changes of the null-cell numbers. The concentrations of total white blood cells, total lymphocytes, B-cells, and monocytes did not change significantly. Our results are consistent with data reported in the literature on follow-up studies of lymphocyte subpopulations in patients with myasthenia gravis undergoing treatment with ACTH and corticosteroids, respectively. Recent experimental findings indicate that T-helper cell activity can be regulated by a negative feedback control mechanism. In consideration of these reports, we discuss the significance of changes in the distribution of lymphocyte subpopulations for the therapeutic action of ACTH and corticosteroids in MS. PMID- 6247877 TI - Encephalomyelitis with polyneuropathy. AB - Four cases of progressive polyneuropathy and bulbar encephalitis and/or myelitis are described. A carcinoma was found in only one of the cases. It is emphasized that this syndrome may occur in the absence of malignant tumors. PMID- 6247878 TI - A retrospective study of 869 cases reported to the Finnish cancer registry between 1962 and 1968. PMID- 6247879 TI - Activation of complement by antibodies to the keratosulphate-like host antigen of Sendai virus. AB - Sendai virus is haemolytic against erythrocytes from different species. Pre treatment of Sendai virus with antibody and complement (C) enhances the haemolytic activity of the virus. This property was used to examine the pathway by which C is activated by Sendai virus antigen-antibody complexes. Antibody against the keratosulphate-like host antigen was used in a monospecific antigen antibody system. Evidence is presented that both the classical and the alternative pathway is activated; the alternative to a much lower extent. PMID- 6247880 TI - Sick cell receptors and disease. PMID- 6247881 TI - Plasma ACTH in patients with bronchogenic carcinoma. AB - Immunoreactive ACTH before and five hours after administration of 2 mg of dexamethasone was determined in patients examined in hospital for abnormalities on chest X-ray. Thirty patients had primary bronchial cancer, 15 had other lung conditions, mostly inflammatory infiltrations. The mean total ACTH and ACTH after dexamethasone suppression were significantly higher in the patients with bronchial cancer than in patients with other lung lesions or healthy controls. ACTH in plasma after administration of glucocorticoids was predominantly big ACTH. Several of the cancer patients had, however, ACTH levels within the same range as the other subjects. These results indicate that plasma ACTH determinations are of limited value as tumour markers for the detection of lung cancer although it is still possible that repeated sampling in patients with elevated ACTH levels may be of value when monitoring the therapy. PMID- 6247882 TI - [Vascular tumors of the lower urinary tract in children]. PMID- 6247883 TI - Membrane cooperative enzymes as a tool for the investigation of membrane structure and related phenomena. PMID- 6247884 TI - Activation of arachidonic acid turnover in adrenal phospholipids by ACTH, A23187, and Ca2+. PMID- 6247885 TI - Glucocorticoids and the prostaglandin system in adipose tissue. PMID- 6247886 TI - Effects of platelet aggregation and adenosine 3':5'-monophosphate on the synthesis of thromboxane B2 in human platelets. PMID- 6247887 TI - Evidence for separate PGD2 and PGF2 alpha receptors in the canine mesenteric vascular bed. PMID- 6247888 TI - Evaluation of prostaglandin and prostacyclin antagonism at platelet receptors by aggregometry. PMID- 6247889 TI - 3H-PGD2 binding by intact human platelets. PMID- 6247890 TI - Prostaglandin-specific binding to several microsomal fractions from bovine myometrium. PMID- 6247891 TI - Prostaglandin receptor: induction of density changes in rat liver plasma membrane. PMID- 6247892 TI - Biochemical and pharmacological evaluation of thromboxane synthetase inhibitors. PMID- 6247893 TI - Endogenous prostaglandin E2 production inhibits proliferation of polyoma virus transformed 3T3 cells: correlation with cellular levels of cyclic AMP. PMID- 6247894 TI - Mechanism underlying the inhibition of platelet aggregation by eicosapentaenoic acid and its metabolites. PMID- 6247896 TI - Calcium, histamine, and pentagastrin: speculations about the regulation of gastric acid secretion at cellular level. AB - The acid secretory response to acetylcholine, histamine, pentagastrin and db-cAMP was studied in dependence of serosal calcium and magnesium level in the isolated whole stomach of the mouse. Histamine- or db-cAMP-induced acid secretion from isolated stomach was not dependent on calcium. Secretory responses to pentagastrin and acetylcholine were strongly diminished in the absence of serosal calcium. Reduction of serosal magnesium concentration influenced neither histamine- nor pentagastrin-induced secretion. The calcium-antagonist verapamil reduced only acid response to pentagastrin. A working hypothesis has been discussed to understand the possible role of calcium in the regulation gastric acid secretion. PMID- 6247895 TI - Histamine and peptic ulcer: influence of sample-taking on the precision and accuracy of fluorometric histamine assay in biopsies of human gastric mucosa. AB - From a methodological point of view the relevance of clinical-biochemical trials depends on the answers to mainly four complexes of questions: (1) the reliability of the assays in the clinical situation to be tested, (2) the precision and accuracy of sample-taking, (3) the qualification of the design and the protocols in the clinical part of the trial and (4) the usefulness of the time concepts in the trial concerning biorhythms, seasonal influences, psychological trauma of diagnostic procedures and treatment. In this study mainly the second complex of questions was studied intensely. The precision of the fluorometric histamine assay in biopsy specimens from human gastric mucosa depended on several conditions: Biochemical technique, sample preparation and removal of biopsies from gastric mucosa via endoscopy. The CV% of the whole procedure was about 8 times higher than that of the biochemical technique. In clinical-biochemical studies on the significance of histamine or any other hormone (such as gastrin) in any disease (uch as duodenal ulcer) it seems therefore useless to describe the precision of an assay only by the variance of the biochemical technique. Calculation of the histamine content as mean of 3 samples reduced the CV% from 27.2 to 14.9% and should therefore be recommended. PMID- 6247898 TI - Experimental maedi infection in sheep. 1. Detection of virus, clinical course, histopathology. PMID- 6247899 TI - Plasma progesterone increments in sows treated with ACTH. PMID- 6247900 TI - The effect of cadmium on indicator bacteria in sewage. PMID- 6247897 TI - Effect of adjuvant arthritis on collagenase and certain lysosomal enzymes in relation to the catabolism of collagen. AB - The activity of collagenase, cathepsin B1, cathepsin D and Hyaluronidase was determined in skin, bone, liver, kidney, spleen and serum of adjuvant induced arthritic rats during the acute and chronic phase of the disease. Collagenase was assayed directly in tissue extract by a solution method using radioactive labelled substrate. The activity of collagenase, cathepsin B1 and D was found to increase significantly at both phases of the disease. The activity of hyaluronidase decreased significantly in liver, kidney and spleen of arthritic rats, while in skin, bone and serum no significant change was observed. The results are discussed with respect to catabolism of collagen in adjuvant induced arthritis. Prednisolone and L-thyroxine were administered to arthritic rats and the activity of collagenase, cathepsin B1, cathepsin D and hyaluronidase was determined in the treated groups during the acute and chronic phase of the disease. Prednisolone was found to suppress the development of arthritis which, in turn, decreased the increased activity of collagenase and lysosomal enzymes cathepsin B1 and D in tissues and serum of arthritic rats. L-Thyroxine was found to slowly diminish the development of inflammation and its beneficial action was found in mesenchymal tissues and skin of arthritic rats but not in bone. PMID- 6247901 TI - Spontaneous clostridial infection and malignancy. PMID- 6247903 TI - Unusual intrathoracic complications in Wilms tumor. AB - Five children with intrathoracic metastases from Wilms tumor are presented. In two patients pneumothoraces developed, and in one patient pneumonitis developed secondary to a primary intrabronchial metastasis. Two other patients had paraspinal widening from metastases to paraaortic or posterior mediastinal lymph nodes. These are extremely rare complications of metastatic Wilms tumor. PMID- 6247902 TI - Low efficacy radiography of children. AB - Radiographic procedures performed at a 100-bed pediatric hospital were reviewed jointly by a radiologist and the primary physician staff. The reviewers judged several procedures to be performed unnecessarily, with undue patient risk or cost. Low efficacy examinations were divided into two categories: (1) low-yield examinations with significant gonadal radiation as well as significant cost, and (2) low-yield examinations with low gonadal radiation but significant cost. A joint policy recommendation was then delivered to the house staff concerning appropriate indications for the performance of these low-yield procedures. This active review process is submitted as a model for other medical facilities that seek to reduce risk and cost to the pediatric patient. PMID- 6247904 TI - High-fiber diet and colorectal disease. PMID- 6247905 TI - Alternatives to institutionalization. AB - If the family physician is to avoid institutionalizing his elderly patients unnecessarily, he must arrange for a comprehensive medical, psychologic, social and financial assessment of all his elderly patients under active treatment. He must contact or organize home health services so that his patients can obtain nursing, homemaker and social work services, meals-on-wheels and other voluntary assistance. He should promote the development of day care and other services that will help maintain the independence of his elderly patients. PMID- 6247906 TI - Evidence and mechanism for pectin-reduced intestinal inorganic iron absorption in idiopathic hemochromatosis. AB - The intestinal absorption of iron was measured in 13 patients suffering from idiopathic hemochromatosis by using a double radiotracer technique. For each patient, iron absorption was determined in the fasting state, i.e., under basal conditions, and after an oral indigestible fiber load (9 g/m2 of body surface) with either pectin (group I: eight patients) or cellulose (group II: five patients). The results were compared with those from a group of seven normal control subjects investigated under basal conditions. The patients with haemochromatosis (groups I and II) had a significant increase in the basal value of fractional iron absorption as compared with controls. In the patients of group I, the pectin induced a significant fall in fractional iron absorption (P less than 0.02). In group II, iron absorption rates remained unchanged whether or not cellulose was given. Furthermore, we found in vitro that pectin had a high iron binding activity, while cellulose bound none. From the present study, we conclude that pectin but not cellulose reduces iron absorption by forming unabsorbable complexes with dietary iron. Thus, enrichment of the diet with foods providing significant amounts of noncellulosic dietary fibers, such as pectin, may be useful in the management of hemochromatosis patients. PMID- 6247907 TI - Probable linkage between the human galactose-1-P uridyl transferase locus and 9qh. AB - Evaluation of a family in which electrophoretic variants of the eznyme galactose 1-phosphate uridyl transferase (GALT) and 9qh variants occur demonstrates close linkage between these two traits: lod score of 3.67 at theta = 0. Taken with information indicating GALT is on the short arm of chromosome 9, these linkage data suggest that this locus is close to the centromere on the short arm of chromosome 9. PMID- 6247909 TI - Studies on the attainment of normocalcemia in patients with pseudohypoparathyroidism. AB - Basal serum calcium and parathyroid hormone (PTH) levels were measured, and urinary excretion of cyclic adenosine monophosphate (AMP) and phosphate was determined before and after the infusion of 250 U of PTH in four patients with pseudohypoparathyroidism when they were hypocalcemic and again when they spontaneously became normocalcemic. These data were compared to those observed in a group of patients with pseudohypoparathyroidism before and after they became normocalcemic after treatment with vitamin D and calcium. Serum PTH levels were very high in patients with untreated pseudohypoparathyroidism and decreased, although not to normal, when normocalcemia occurred either spontaneously or through treatment. Of the four patients who became normocalcemic spontaneously, basal and PTH-stimulated urinary excretion of cyclic AMP, and clearance of phosphate increased. These changes were all significantly different from the changes which occurred when patients became normocalcemic as a result of treatment with vitamin D anc calcium. The factors which govern the apparent increased renal sensitivity to endogenous and exogenous PTH when normocalcemia develops spontaneously in patients with pseudohypoparathyroidism remain to be explained. However, these changes are dissimilar from those which occur from treatment with vitamin D anc calcium. PMID- 6247911 TI - Chronic airflow obstruction in Fabry's disease. AB - Seven patients with Fabry's disease, an x-linked sphingolipid storage disorder, were evaluated for the presence and extent of airway obstruction. All were found to have significant obstruction to airflow. In addition, evaluation of their airway epithelial cells obtained by bronchoscopy demonstrated that these cells contained inclusion bodies consistent with deposits of ceramide trihexoside, suggesting that part of their functional obstruction to airflow may be secondary to intrinsic airway disease. Although all of the study population had evidence of airflow obstruction, the impairment was much worse in those who smoked, implying that even mild cigarette smoking is particularly hazardous to patients with Fabry's disease. PMID- 6247910 TI - Prophylactic granulocyte transfusions during human bone marrow transplantation. AB - Thirty-eight uninfected patients undergoing bone marrow transplantation were assigned at random to receive prophylactic granulocyte transfusions and oral nonabsorbable antibiotics (group 1) or oral nonabsorbable antibiotics alone (group 2) when their neutrophil count fell below 0.5 x 10(9)/liter. The two groups were comparable in terms of age, sex, underlying disease, immunosuppressive therapy and days of neutropenia. There were three cases of septicemia (all due to gram-positive organisms) in group 2 and none in group 1 (p = 0.23). There was no difference in the incidence of other documented infections, and survival between the two groups was comparable. Recipients of prophylactic granulocyte transfusions had a significantly higher incidence of cytomegalovirus (CMV) infections (13 of 18 versus six of 17, p = 0.043). These data suggest that prophylactic granulocyte transfusions may prevent septicemia, have no effect on other infections or survival in patients undergoing bone marrow transplantation, and are associated with a higher incidence of CMV infection. Oral nonabsorbable antibiotics alone are equally effective in preventing serious infections in bone marrow transplant recipients. PMID- 6247908 TI - Construction of a genetic linkage map in man using restriction fragment length polymorphisms. AB - We describe a new basis for the construction of a genetic linkage map of the human genome. The basic principle of the mapping scheme is to develop, by recombinant DNA techniques, random single-copy DNA probes capable of detecting DNA sequence polymorphisms, when hybridized to restriction digests of an individual's DNA. Each of these probes will define a locus. Loci can be expanded or contracted to include more or less polymorphism by further application of recombinant DNA technology. Suitably polymorphic loci can be tested for linkage relationships in human pedigrees by established methods; and loci can be arranged into linkage groups to form a true genetic map of "DNA marker loci." Pedigrees in which inherited traits are known to be segregating can then be analyzed, making possible the mapping of the gene(s) responsible for the trait with respect to the DNA marker loci, without requiring direct access to a specified gene's DNA. For inherited diseases mapped in this way, linked DNA marker loci can be used predictively for genetic counseling. PMID- 6247912 TI - Vertebral compression fractures with accelerated bone turnover in a patient with Cushing's disease. PMID- 6247913 TI - Urinary acidification in a patient with glucose-6-phosphate dehydrogenase deficiency. A reevaluation of the role of the hexose monophosphate shunt in renal acid secretion. AB - The relationship between renal metabolism and urinary acidification is poorly understood. During the past decade evidence has accrued to suggest that the hexose monophosphate (HMP) shunt might serve in the process of urinary acidification by providing reducing equivalents for a redox-coupled membrane bound proton pump that could transport protons into the tubular lumen. The major support for this hypothesis has come from the finding that HMP shunt activity increases with acute and chronic metabolic acidosis. In the present study, we examine the urinary acidification capacity of a young man with severe erythrocyte glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and with unmeasurable G-6 PD activity in renal cortical tissue. We found that despite unmeasurable G-6-PD activity in renal tissue, the patient was capable of generating a maximally acid urine and increasing total acid secretion. Our findings suggest that the HMP shunt may not be necessary for the urinary acidification process. PMID- 6247914 TI - Ambulatory evaluation of nephrolithiasis. Classification, clinical presentation and diagnostic criteria. AB - Using the ambulatory protocol previously described, 241 patients with nephrolithiasis were evaluated. They could be categorized into 10 groups from the results obtained. Absorptive hypercalciuria type I (87 per cent male) comprised 24.5 per cent and was characterized by normocalcemia, normal fasting urinary calcium (less than 0.11 mg/100 ml glomerular filtration), an exaggerated urinary calcium following an oral calcium load (greater than 0.20 mg/mg creatinine), normal urinary cyclic adenosine monophosphate (AMP) (less than 5.4 nmol/100 ml glomerular filtration) and serum parathyroid hormone (PTH), and hypercalciuria (greater than 200 mg/day during a calcium- and sodium-restricted diet). Absorptive hypercalciuria type II (50 per cent male) accounted for 29.8 per cent; its biochemical features were the same as those for absorptive hypercalciuria type I, except for normocalciuria during a restricted diet and low urine volume (1.42 +/- 0.55 SD liter/day). Renal hypercalciuria (56 per cent male), disclosed in 8.3 per cent, was represented by normocalcemia and high values for fasting urinary calcium (0.160 +/- 0.054 mg/100 ml glomerular filtration), urinary cyclic AMP (6.80 +/- 2.10 nmol/100 ml glomerular filtration) and serum PTH. Primary hyperparathyroidism (57 per cent female), accounted for 5.8 per cent, typically included hypercalcemia, hypophosphatemia, hypercalciuria and high urinary cyclic AMP. Hyperuricosuric calcium urolithiasis (100 per cent male) comprised 8.7 per cent, and was characterized by hyperuricosuria (776 +/- 164 mg/day) and urinary pH exceeding pK for uric acid (5.91 +/- 0.33). In enteric hyperoxaluria (60 per cent female), encountered in 2.1 per cent of cases, urinary oxalate was increased (6.29 +/- 13.2 mg/day). Noncalcium-containing stones were found in 2.1 per cent of the patients with uric acid lithiasis (100 per cent male) and in another 2.1 per cent of the patients with infection lithiasis (60 per cent female). These conditions were typified by low urinary pH (5.29 +/- 0.12) and high urinary pH (6.69 +/- 1.16), respectively. Renal tubular acidosis was found in one patient (male, 0.4 per cent). In 10.8 per cent of the patients (81 per cent male), no metabolic abnormality could be found, although urine volume was low (1.41 +/- 0.51 liter/day). Hypercalciuria could not be differentiated between absorptive hypercalciuria and renal hypercalciuria in 5.4 per cent of the patients. Thus, this ambulatory protocol disclosed a physiologic disturbance in nearly 90 per cent of the cases and provided a definitive diagnosis in 95 per cent of the patients. PMID- 6247915 TI - Glioblastoma multiforme. AB - Glioblastoma multiforme is the most common primary brain tumor of adults, as well as the most malignant. Its etiology is unknown, but the tumor is thought to arise through dedifferentiation of adult astrocytes. It occurs most frequently between the ages of 40 and 60, in men more often than in women (1.5:1). Important early symptoms include subtle personality change, headache, weakness, and intellectual impairment; specific complaints and physical findings depend on the location of the lesion. The initial diagnostic test should be a CT-scan; it will detect more than 90% of malignant astrocytomas. Surgery remains the cornerstone of treatment; patients receiving radical debulking have a median survival of 8 months compared to the 3 month survival of unoperated cases. Modern neurosurgical technique, neuroanesthesia, mannitol, and corticosteroids have reduced the surgical mortality to 3%. Most patients also receive 4500 rads of whole-brain irradiation and 1800 rads to the operative site; radiotherapy increases the median survival of operated patients by 2 to 3 months. An additional small increment in survival time and some improvement in quality of survival can be achieved by nitrosourea chemotherapy; the latter is usually given as 100 mg/m2/day x 3 days of BCNU every eight to ten weeks. Experimental treatments under study include the use of radiosensitizers, the role of immunotherapy and the application of microwave induced hyperthermia. Two-year survival remains 10% to 20%, and there are virtually no five-year survivors. An optimal combined modality treatment plan, one in which each cellular compartment of this truly multiforme tumor is effectively addressed, remains to be designated. PMID- 6247916 TI - Serum angiotension-converting enzyme activity during normal pregnancy. PMID- 6247917 TI - Nummular keratitis associated with infectious mononucleosis. AB - A 16-year-old boy had a severe case of infectious mononucleosis with a rising titer to the Epstein-Barr virus. The patient had developed a nummular keratitis apparently associated with this illness. Because infectious mononucleosis or infection by the Epstein-Barr virus is often subclinical, and many cases of nummular keratitis have been classified as idiopathic in the past, a possible association between the two in such cases should be considered. PMID- 6247919 TI - Influence of sodium balance on ACTH/adrenal corticosteroid dose-response curves in the dog. AB - In order to define short-term ACTH/corticosteroid dose-respone characteristics, we infused ACTH for 1 h at each of five incremental rates into pedigreed male beagle dogs in four different states of sodium balance. Progressive sodium depletion was associated with progressive increased in basal (pre-ACTH) plasma levels of renin, angiotensin II, aldosterone, 18-hydroxycorticosterone (18-OH-B), and 18-hydroxy-11-deoxycorticosterone (18-OH-DOC). Administration of dexamethasone significantly reduced the preinfusion levels of cortisol, aldosterone, 18-OH-B, and 18-OH-DOC. The threshold dose of ACTH required to elicit an aldosterone response during low-sodium intake was similar to that for cortisol, but was higher during normal or high-sodium intake. Steepest portions of the dose-response curves were at lower rates of ACTH infusion for cortisol than for aldosterone, and maximum increment was much greater for cortisol (60 fold) than for aldosterone (12-fold). Whereas the slopes of ACTH/aldosterone and ACTH/18-OH-B dose-response curves were steepened by lower sodium diets, the ACTH/cortisol response was significantly flattened by severe sodium depletion. We conclude that ACTH is a potent and direct-acting short-term regulator of aldosterone secretion, subject to modification by altered sodium balance. PMID- 6247918 TI - Complement receptors on normal human lymphocytes containing parallel tubular arrays. AB - Membrane complement receptors have been identified on a subpopulation of normal lymphocytes containing cytoplasmic inclusions called parallel tubular arrays (PTA) using two different rosetting techniques. The first technique utilizes as indicator cells erythrocytes that were coated with complement by the classic pathway of complement activation (EAC rosettes). The second technique utilizes as indicator cells Salmonella typhi, which were coated with complement by the alternate pathway of complement activation (FBC rosettes). In the latter technique, lipopolysaccharide material in the bacterial cell wall directly activates complement without the use of a sensitizing antibody. This eliminates binding of marker particles by lymphocytes having Fc receptors. The presence of PTA lymphocytes at the center of EAC rosettes and FBC rosettes was demonstrated by electron microscopy, indicating that the PTA lymphocyte has a complement receptor. Examination of FBC rosettes revealed that the adherent complement coated bacteria were usually partially surrounded by pseudopodal extensions of the PTA lymphocyte. In addition, some PTA lymphocytes phagocytized the complement coated bacteria but not the complement-inactivated bacteria. These phagocytic cells were placed in the lymphocytic series instead of the monocytic series by virtue of complete lack of endogenous peroxidase activity. PMID- 6247920 TI - Stereospecific stimulation of brown adipocyte respiration by catecholamines via beta 1-adrenoreceptors. AB - Regulation of respiration by catecholamines was studied in adipocytes isolated from interscapular brown adipose tissue of warm-acclimated rats by rapid digestion of collagenase. (-)-Norepinephrine stimulated adipocyte respiration 10 12 times above basal values in less than 3 min. (Vmax = 410 +/- 29.5 nmol O2 . min-1 . 10(-6) cells-1). Stimulated respiration remained stable for at least 20 min, provided that cells were incubated in balanced salt media containing bicarbonate. The maximal capacity of total brown adipose tissue for norepinephrine-stimulated respitarion was estimated at 1.5 ml O2/min per rat. beta-Adrenergic agonists increased calorigenesis stereospecifically with an order of potency expected for respiratory stimulation via adrenoceptors of the beta 1 subtype: (-)-isoproterenol (1/2 Vmax = 2 nM) greater than (-)-norepinephrine (1/2 Vmax = 20 nM) approximately equal to (-)-epinephrine (1/2 Vmax = 40 nM) greater than corresponding (+)-stereoisomers. The alpha-adrenergic agonist phenylephrine (1/2 Vmax = 5 microM) stimulated adipocyte respiration as rapidly and as effectively as beta-agonists. Although alpha-adrenoreceptors are present in brown adipose tissue, studies with alpha- and beta-adrenergic antagonists revealed that norepinephrine elicits thermogenesis at physiological concentrations (less than or equal to 1 microM) predominantely via beta 1 adrenergic pathways. PMID- 6247921 TI - Inorganic anion transport in kidney and intestinal brush border and basolateral membranes. AB - The efflux of inorganic anions from purified brush border and basolateral membrane vesicles from dog kidney cortex was measured under equilibrium exchange conditions. Marked differences in temperature sensitivity and effects of inhibitors were found between the Cl and SO4 transport pathways and between the two types of membranes. SO4 transport in both brush border and basolateral membranes was markedly reduced by cooling, but significant inhibition by 4,4' diisothiocyano-2,2'-disulfonic stilbene (DIDS) was only observed in basolateral vesicles. In contrast, Cl efflux from both types of vesicles was neither substantially inhibited by DIDS nor by lowering the temperature to 0 degrees C. Phosphate efflux from basolateral membrane vesicles was found to be only partially sensitive to DIDS. Attempts to label the stilbene-sensitive SO4 pathway in basolateral vesicles using [3H2]DIDS as a marker were unsuccessful due to the nonspecific labeling of many membrane components. The asymmetry in inorganic anion transport behavior exhibited by brush border and basolateral membrane vesicles from dog renal proximal tubule was also observed in equivalent vesicles prepared from rat small intestine. PMID- 6247922 TI - Effect of collagenase and ouabain on renal cell volume in hypotonic media. AB - Proximal straight tubules (S2 segments) swell rapidly in hypotonic media, but within a few minutes their volume returns toward control levels due to extrusion of K, Na, Cl, and water from the cytoplasm. In the present studies we determined the extent to which hydrostatic pressure (derived from the elastic tubule basement membrane (TBM) as the tubule enlarged in hypotonic medium) contributed to the regulation of cell volume. Removal of the TBM by collagenase had no effect on cell volume regulation in otherwise normal tubules. By contrast, tubules treated with ouabain, though they appeared to regulate their volumes in hypotonic media, were unable to do so in the presence of glycoside if the TBM had been removed with collagenase. This latter result is interpreted to show that hydrostatic pressure generated by extension of the TBM can cause "apparent" volume regulation when the sodium pump is blocked by ouabain. We conclude that normal proximal renal tubules regulate cell volume in hypotonic solutions by mechanisms that are dependent on the normal operation of the classical sodium pump. PMID- 6247924 TI - Mechanism of physiological hypoxia-induced depression of vascular smooth muscle contraction. PMID- 6247923 TI - Effect of glucagon on ion transport in mouse intestine. AB - Effects of glucagon (GN) on short-circuited mouse intestine were studied. GN (30 microgram . ml-1), added to the serosa of intestine mounted in an Ussing chamber and bathed in glucose-free Ringer, induced significant increases of 43% in serosal-to-mucosal Cl- flux (Js leads to m Cl), 315% in net Cl- secretion (Jnet Cl), 85% in net residual flux (J net R), 61% in short-circuit current (Isc), and 44% in open-circuit potential difference (PD). The mucosal-to-serosal Cl- flux and both unidirectional Na+ fluxes (Jm leads to s Na and Js leads to m Na) were unchanged. In a glucose Ringer bathing medium, GN exhibited no significant effects on ion fluxes and electrical parameters. To eliminate the possibility that observed GN-induced changes in PD and Isc were partially due to changes in membrane surface charge, the effects of GN in Cl- -free Ringer were studied. Under these conditions, GN had no effect on electrical parameters. Furthermore, GN elicited no effect on cAMP levels in either the presence or absence of glucose. These findings suggest that 1) the effect of GN on Jnet Cl is masked in the presence of glucose, 2) GN-induced increases in Isc and PD are a reflection of the increase in Jnet Cl and are neither due to changes in membrane surface charge nor to an increase in net Na+ flux, and 3) GN-induced secretory diarrhea is in part due to changes in electrolyte transport. PMID- 6247925 TI - Release of autonomic neuromediators by local ventricular electrical stimulation. AB - Trains of electrical stimuli were applied to the ventricular epicardium in pentobarbital-anesthetized dogs. The trains, delivered during the absolute refractory period via Walton-Brodie strain gauge arches, resulted in a highly localized potentiation of ventricular contractile force. The magnitude of the potentiation was directly related to the intensity of the trains. The positive inotropic response of either ventricle to trains of stimuli was abolished following chronic cardiac denervation or beta-adrenergic blockade with tolamolol, indicating that the response was probably mediated by the excitation of local sympathetic nerve fibers. Following the elimination of adrenergic influences, a slight negative inotropic response to trains of stimuli was observed in some animals. Administration of atropine blocked the negative inotropic response. When the adrenergic system was intact the administration of atropine resulted in a significant augmentation of the positive inotropic response of both ventricles to trains of stimuli. Thus in addition to norepinephrine release, it also appeared that electrical stimulation of the ventricles resulted in activation of local parasympathetic fibers with subsequent release of acetylcholine. PMID- 6247926 TI - Intravascular mechanoreceptor modulation of renal sympathetic nerve activity in the cat. AB - Experiments were performed in chloralose-anesthetized cats to characterize intravascular mechanoreceptro input to renal nerve activity in the intact and vagotomized sinoaortic-denervated states. High-pressure intravascular mechanoreceptors were stimulated by rises in arterial pressure caused by norepinephrine. Low-pressure intravascular mechanoreceptors were stimulated by progressive blood volume expansion (14-23%) at a rate of 4.4 or 17.6 ml/min. In addition, veratrine was used to stimulate directly both high- and low-pressure receptors. In the intact animal the administration of norepinephrine or blood volume expansion was associated with substantial decreases in renal nerve activity. Veratrine also caused a large dose-related decrease in renal nerve activity. However, in the vagotomized sinoaortic-denervated animal there was no change in renal nerve activity with norepinephrine, volume expansion, or veratrine administration. These experiments demonstrate that the major afferent pathways for renal sympathetic circulatory reflexes are confined to the carotid sinus and aortic and vagus nerves. No evidence was found for a significant contribution from sympathetic afferent nerves. PMID- 6247927 TI - Effect of converting enzyme inhibition on glucocorticoid hypertension in the rat. AB - The renin-angiotensin system was evaluated by inhibition of converting enzyme (CEI) and by testing sensitivity to angiotensin II (AII) in sodium-depleted rats made hypertensive by methylprednisolone (MP), 20 mg/kg im. During a 2-wk period blood pressure rose 38 +/- 4 mmHg (P less than 0.001) in MP and 3 +/- 4 mmHg in controls. After pentobarbital anesthesia, intra-arterial pressure and dose response curves to AII were determined, before and after SQ14225 (d-3-mercapto-2 methylpropranoyl-l-proline) (1 mg/kg iv). CEI reduced pressure significantly in both MP and controls, although the decrease was smaller in the former (P less than 0.05). Pressor responses to AII were nearly identical in MP and controls and were enhanced to a similar extent by CEI. Ganglionic blockade with pentolinium tartrate, given after CEI, did reduce the pressure in both groups to equal levels. Responses to AII after pentolinium were similar to those obtained after CEI alone. These results indicate that the renin component of glucocorticoid hypertension during sodium deficiency is smaller than that of the normotensive controls. No evidence of glucocorticoid-induced vascular hypersensitivity to AII was detected in this model of experimental hypertension. PMID- 6247928 TI - Management of intravenous extensions of endocrine tumors and prognosis after surgical treatment. AB - The capacity of endocrine neoplasms to give rise to intravenous tumor extensions is a feature that is recognized preoperatively by the use of venography employed primarily for tumor localization. A series of adrenocortical tumors, a pheochromocytoma and an extraadrenal chromaffin tumor are reported in which the intravenous tumor component was recognized and the surgical approach was modified to include extirpation of the intravascular tumor. Although intravenous tumor propagation has implied a grave prognosis because of the possibility of blood borne metastases from the intravascular tumor or physiologic disruption from clot or tumor embolus, resection designed for cure, including distal venous control and tumor thrombectomy, was carried out in each patient. Wider application of preoperative venography enables recognition of these intravenous neoplastic extensions from endocrine tumors; the results of surgical management suggest that this invasive feature should not be a grave prognostic indicator that inhibits attempt at operative eradication of the primary tumor and its intravenous extension. PMID- 6247929 TI - [Steroid secretion in prolonged pregnancy. III. Corticosteroid and ACTH secretion in prolonged pregnancy]. PMID- 6247930 TI - [Artificial regulation of the generative functions of men by means of contraceptive agents]. PMID- 6247931 TI - Antibiotics--their administration, choice and prophylactic use. AB - A wider range of antibiotics is now available with the advent of two new cephalosporins--cefamandole and cefuroxime, and the first cephamycin--cefoxitin. These drugs may be particularly useful in the treatment of septicaemia, and when combined with ticarcillin are effective against nearly all pathogens. Cefuroxime can be given intramuscularly. Intravenous cotrimoxazole must be given in large doses to achieve therapeutic concentrations in the cerebrospinal fluid. The correct use of antibiotics for prophylaxis demands an accurate knowledge of the organisms likely to cause infection and the most efficient way of using the antibiotics to prevent that infection. There is little argument about the need for prophylaxis to prevent recurrent rheumatic heart disease or tetanus from a contaminated wound. However, in the various areas of surgery a wide range of antibiotics is used not always as a result of controlled trials having proved their value. Non-surgical situations for prophylaxis are briefly reviewed. PMID- 6247932 TI - Free metal ion depletion by "Good's" buffers. II. N-(2-acetamido)-2 aminoethanesulfonic acid (ACESH): complexes with calcium(II), magnesium(II), manganese(II), cobalt(II), zinc(II), nickel(II), and copper(II). PMID- 6247933 TI - Use of terbium fluorescence enhancement as a new probe for assessing the single strand content of DNA. PMID- 6247934 TI - Large-scale purification of angiotensin I-converting enzyme from human plasma utilizing an immunoadsorbent affinity gel. PMID- 6247935 TI - Microcentrifuge desalting: a rapid, quantitative method for desalting small amounts of protein. PMID- 6247936 TI - Synthesis of deoxynucleoside-5'-tri-3'-diphosphates by Streptomyces adephospholyticus ATP:nucleotide pyrophosphokinase. PMID- 6247937 TI - Supports for reverse-phase high-performance liquid chromatography of large proteins. PMID- 6247938 TI - A quantitative collagen film collagenase assay for large numbers of samples. PMID- 6247939 TI - Determination of acid hydrolases in human platelets. PMID- 6247940 TI - Counting efficiency in the radioassay of 3H- and 14C-labeled lipids adsorbed on silica gel by liquid scintillation. PMID- 6247941 TI - Changes of ejaculation due to suppression of noradrenaline biosynthesis by diethyldithiocarbamate in dogs: a supplemental report with reference to changes of posterior urethral pressure. AB - In the preceding paper (Kimura et al.-1979) it was reported that diethyldithiocarbamate suppresses ejaculation, although penile erection is maintained, and that the suppression is not mediated by the central nervous system but by the decrease of catecholamine contents in the organs relating to sperm transport. In this paper, changes of ejaculation following administration of diethyldithiocarbamate was studied with the posterior urethrogram; measurement of the posterior urethral pressure during hypogastric nerve stimulation. From the results obtained in this study the above results were confirmed. It was also confirmed that both seminal emission and ejaculation are under the influence of an alpha-adrenergic receptor mechanism. Also, a dopamine receptor mechanism was suspected to be present in the male accessory sexual glands. PMID- 6247942 TI - [Functional topographic characteristics of liver insufficiency during the performance of hemosorption according to liver radioisotope study date]. PMID- 6247943 TI - Serum angiotensin-converting enzyme activity as an indicator of prognosis in sarcoidosis. AB - The relationship between the clinical course of sarcoidosis and serum angiotensin converting enzyme (EC 3.4.15.1) activity was analyzed by observing 51 patients with sarcoidosis during a period of more than 1 yr. The patients were grouped into 3 categories irrespective of treatment: (1) sarcoid lesions in the chest disappeared within 1 yr, (2) sarcoid lesions remained for more than 1 yr with little improvement, (3) sarcoid lesions disappeared within 1 yr, but then relapsed. In group 1 (33 cases), the serum angiotensin-converting enzyme activity decreased from 35.9 +/- 2.0 to 22.0 +/- 1.3 nmol/ml/min after the chest roentgenogram cleared (P less than 0.005). In group 2 (12 cases), the mean serum angiotensin-converting enzyme activity after treatment was not significantly reduced, paralleling the lack of improvement. In group 3 (6 cases), a good correlation was observed between serum enzyme activity and clinical course. These findings indicate that serum angiotensin-converting enzyme activity is an indicator of the clinical course of sarcoidosis. PMID- 6247944 TI - Cytomegalovirus as a cause of cecal ulcer with massive hemorrhage in a renal transplant recipient. AB - Although cytomegalovirus disease following renal transplantation occurs frequently, ulcerative lesions of the gastrointestinal tract are not common. This report describes a patient with a single large cecal ulcer, with cytomegalovirus inclusion bodies located in the ulcer bed. The patient presented with massive rectal bleeding necessitating a right hemicolectomy. No other manifestations of systemic cytomegalovirus disease were present in this patient. PMID- 6247945 TI - Anal stenosis and megarectum in the elderly. AB - Anal stenosis, an often unrecognized condition causing acute colonic obstruction in the elderly, is described with reference to three cases. Initial management should include: 1) digital dilatation and rectal examination; 2) sigmoidoscopy; 3) insertion of a rectal tube; 4) correction of fluid and electrolyte imbalance. Sufficient experience is not available to predict the results of sphincterotomy or anoplasty, both of which may result in incontinence, and conservative measures may suffice in most cases. Prevention of this condition may be achieved by adequate intake of dietary fiber or regular bulk laxatives in these debilitated patients. PMID- 6247946 TI - Sustained remission of Cushing's disease with mitotane and pituitary irradiation. AB - Low doses of mitotane were given orally to 36 patients with Cushing's disease, concurrently with or after pituitary cobalt irradiation. Clinical and biochemical remission occurred in 29. The response to treatment occurred early in 17 patients and late in 12. The different pattern of response to mitotane was not related to the dose given or to its serum level. Early biochemical indicators of adrenal suppression with mitotane were a sharp decrease in adrenal response to the infusion of ACTH and in plasma levels of dehydroepiandrosterone sulfate. Although mitotane was given together with pituitary irradiation, initial remission was due mainly to the adrenal effect of mitotane. Plasma ACTH levels were still elevated when cortisol had returned to normal. In seventeen of the 29 patients who responded to treatment drug therapy has been discontinued, and they remain in remission of Cushing's syndrome. Side-effects have been dose dependent, with anorexia, nausea, decreased memory, and gynecomastia in men being the commonest. PMID- 6247947 TI - Principles of membrane receptor physiology and their application to clinical medicine. AB - The clinical involvement of membrane receptors for hormones, neurotransmitters, and other molecules of interest is reported with increasing frequency. In this review, the terminology of the hormone-receptor field is defined, and the current concepts of the participation of membrane receptors in the mechanism of hormone action are outlined. Several major developing concepts of receptor regulation and function, including spare receptors and down regulation of receptor number, provide a basis for understanding the physiology and pathophysiology of cellular sensitivity to specific hormones. The relation of these concepts to the pathophysiology of various metabolic disorders is discussed. Clinical disorders in which membrane receptors play a central role are reviewed, including Graves' disease and myasthenia gravis, which involve antireceptor antibodies, and familial hypercholesterolemia and various conditions of hormone resistance that often involve a marked decrease in receptor number as the primary pathogenic factor. The significance of receptor physiology in other selected areas of clinical medicine is discussed. PMID- 6247948 TI - Purinogenic immunodeficiency diseases: clinical features and molecular mechanisms. AB - Deficiencies of two enzymes that catalyze sequential reactions in the purine catabolic pathway have been causally associated with immunodeficiency states. Adenosine deaminase (ADA) deficiency results in severe combined immunodeficiency disease, while purine nucleoside phosphorylase (PNP) deficiency results in an isolated T-cell defect. Recent work in this area has provided major new insights into the molecular pathology of these syndromes. Deoxyadenosine and deoxyguanosine, substrates that accumulate in ADA and deoxyguanosine, substrates that accumulate in ADA and PNP deficiency, respectively, appear to be selectively phosphorylated by lymphoid cells to the corresponding deoxynucleoside triphosphate, resulting in inhibition of DNA synthesis in these cells. Both deoxynucleosides are far more toxic to cultured T lymphoblasts than to B lymphoblasts. Adenosine and deoxyadenosine may have additional lymphotoxic effects mediated by inhibition of essential methylation reactions. These observations help to explain the immunologic manifestations of ADA and PNP deficiency. Perhaps more important, they lay the foundation for the use of deoxynucleosides or enzyme inhibitors, or both, as selective immunosuppressive and chemotherapeutic agents. PMID- 6247949 TI - [Transferable tetracycline resistance in "Clostridium difficile" (author's transl)]. AB - Tetracycline (Tc) resistance is transferable from a resistant strain of Clostridium difficile to a sensitive strain and this resistance is not curable. Resistances to erythromycin and clindamycin are curable but not transferable. These results suggest for these resistances a plasmid determinism. It is shown that a plasmid-mediated Tc resistance (pIP401) of C. perfringens is also transferable to C. difficile. Tc resistance is inducible in C. perfringens and constitutively expressed in C. difficile. In the Tc-resistant transcipients of C. difficile this resistance is either inducible or constitutive, whether the Tc resistant donor strain was C. perfringens or C. difficile. PMID- 6247950 TI - The use of photoaffinity probes to elucidate molecular mechanisms of nucleotide regulated phenomena. PMID- 6247951 TI - Photoenzyme probes of photodamage to cells and cellular DNA. PMID- 6247952 TI - The use of photoaffinity labels in the study of mitochondrial function. PMID- 6247953 TI - Electrophysiological experiments with photoisomerizable cholinergic compounds: review and progress report. PMID- 6247954 TI - The use of photolabels to probe the ouabain binding site of the (Na, K)-ATPase. PMID- 6247955 TI - Angiographic differential diagnosis of tumors of the glomus caroticum and jugulo tympanicum and of arterio-venous shunts in the head and neck. PMID- 6247956 TI - RNA virus associated antigen in human placenta. AB - Using indirect immunofluorescence microscopy, it was demonstrated that human cytotrophoblast of six to ten weeks gestation contains mouse mammary tumor virus associated antigen. This antigen appeared predominantly in the periphery of the cells. PMID- 6247957 TI - Neurotoxins that act on voltage-sensitive sodium channels in excitable membranes. PMID- 6247958 TI - The role of membrane lipids in receptor mechanisms. PMID- 6247959 TI - Effects and mechanisms of polypeptide neurotoxins that act presynaptically. PMID- 6247960 TI - Protein phosphorylation catalyzed by cyclic AMP-dependent and cyclic GMP dependent protein kinases. PMID- 6247961 TI - Pharmacological receptor determination in endocrine therapy of breast cancer. PMID- 6247962 TI - Radioligand binding studies of adrenergic receptors: new insights into molecular and physiological regulation. PMID- 6247963 TI - Structure-activity relationships of enkephalin-like peptides. PMID- 6247964 TI - [Effect of K+ ions on Bac. polymyxa 153 growth and the biosynthesis of polymyxin B]. AB - The growth of Bac. polymyxa, 153 producing polymyxin B did not change under the effect of various concentrations of potassium ions, while the antibiotic productivity of the cells significantly decreased. A great amount of polymyxin is excreted by the bacteria into the fermentation broth and a certain portion of the antibiotic remains in the cells. Under the experimental conditions the potassium salts slightly changed the pH value of the fermentation broth and probably did not affect polymyxin secretion from the cells into the fermentation broth. PMID- 6247965 TI - Biosynthesis of peptidoglycan in Pseudomonas aeruginosa: comparison of the inhibitory effects of cefotaxime, its anti isomer, and the syn S-oxide compound. AB - The intrinsic effect of three novel methoxyimino derivatives of cephalosporin (cefotaxime [syn HR 756]; its anti isomer, R 02 5328 A; and the syn S-oxide derivative, HR 109) on the biosynthesis of peptidoglycan of Pseudomonas aeruginosa X-48 was investigated. Cefotaxime at very low concentrations (50% inhibition at 0.025 microgram/ml) inhibited the transpeptidase reaction which catalyzes the incorporation and attachment of newly synthesized peptidoglycan to the preexisting cell wall sacculus. The S-oxide compound, HR 109, was a much less efficient inhibitor of this reaction (50% inhibition at 0.55 microgram/ml), whereas the anti isomer of cefotaxime, R 02 5328 A, had no inhibitory effect. All three compounds were quite similar in being relatively poor inhibitors of D alanine carboxypeptidase. PMID- 6247966 TI - Comparative in vitro activity of 1-oxa-beta-lactam (LY127935) and cefoperazone with other beta-lactam antibiotics against anaerobic bacteria. AB - The in vitro activity of 1-oxa-beta-lactam (LY127935), cefoperazone (T-1551), cefuroxime, cefsulodin, cefaclor, cefotaxime, and cefoxitin on 85 anaerobic clinical isolates (30 Bacteroides, 30 Clostridium, 25 Peptococcaceae) was simultaneously determined by the agar dilution test in two different media, Brucella Agar (Difco Laboratories) and Wilkins-Chalgren agar. In Wilkins-Chalgren agar, 90% of Bacteroides were inhibited by (micrograms per milliliter): LY127935, 0.5; T-1551, 64; cefoxitin or cefuroxime, 8; cefsulodin or cefotaxime, 32; and cefaclor, 128. All Clostridia were inhibited in Wilkins-Chalgren by (micrograms per milliliter): LY127935, 4; T-1551, 2; cefoxitin, 6; cefuroxime, 0.12; cefsulodin, 0.5; cefaclor, 1; and cefotaxime, 8. All Peptococccaceae were inhibited by T-1551, cefsulodin or cefotaxime at 4 microgram/ml and by cefoxitin or cefuroxime at 1 to 2 microgram/ml. With cefaclor at 8 microgram/ml, 92% of strains were inhibited, and LY127935 at 16 microgram/ml only inhibited 64% of strains. LY127935 was the most active of the antibiotics tested against Bacteroides, showing good activity against Clostridia and poor activity on Peptococcaceae, whereas T-1551 was more active against Peptococccaceae and had similar activity against Clostridia and poor activity on Bacteroides. There are no significant differences between minimal inhibitory concentrations obtained in Brucella Agar and those obtained in Wilkins-Chalgren. PMID- 6247967 TI - In vitro and in vivo resistance of herpes simplex virus to 9-(2 hydroxyethoxymethyl)guanine (acycloguanosine). AB - In vitro passage of the Patton strain of herpes simplex virus type 1 (HSV-1-P) in the presence of acycloguanosine (ACG) led to the emergence of a highly drug resistant strain (HSV-1-P-ACG-R). Over 1% of virions in 6 of 15 HSV strains tested were able to form plaques in the presence of 10 mumol of ACG on first exposure to the drug. Therefore, there exists among HSV strains a broad range of susceptibilities to ACG, and some strains contain particles which are partially resistant to ACG before ever contacting the drug. HSV-1-P-ACG-R was partially resistant to iododeoxyuridine; conversely, iododeoxyuridine-resistant virus was highly resistant to ACG. ACG-resistant virus (HSV-1-P-ACG-R) was equal to its parent strain (HSV-1-P) in susceptibility to adenine arabinoside. The HSV-1-P-ACG R strain produced corneal lesions in rabbits which were completely refractory to topical treatment with 1% unguent ACG, but responsive to 3% ACG. Partially resistant HSV could be isolated from the eyes of rabbits infected with ACG susceptible virus and treated topically with either 1 or 3% ACG for 6 days. PMID- 6247968 TI - Sensitive assay for measuring tetracycline levels in gingival crevice fluid. AB - An increased interest in the clinical use of antibiotics as an adjunct to periodontal therapy has created a need to determine antibiotic concentrations in fluid obtained from the gingival crevice. For this purpose, an increase in sensitivity beyond that possible with current tetracycline assays is essential because sample volumes of gingival fluid typically obtained are less than 0.5 microliter. This report describes the development of an agar-diffusion assay technique capable of measuring the concentration of tetracycline in samples of gingival crevice fluid in the range of 0.1 to 4.0 microgram/ml. The assay will detect amounts of tetracycline in gingival crevice fluid samples as low as 50 pg. The high sensitivity of this assay was achieved by optimizing the medium depth, inoculum density, agar concentration, pH, period of prediffusion, and selection of basal medium. Use of this assay indicated that the concentration of tetracylcine in gingival crevice fluid was greater than that found in blood and persisted at elevated levels for longer periods. PMID- 6247969 TI - Pathogenicity in mice of strains of herpes simplex virus which are resistant to acyclovir in vitro and in vivo. AB - Mice infected with three different isolates of herpes simplex virus (HSV) and treated with acyclovir (acycloguanosine; ACV) showed low levels of virus replication during the acute phase of infection. However, virus isolated from such treated mice did not show increased resistance to ACV. In contrast, resistant virus was readily isolated in vitro by passaging HSV in the presence of the drug. The degree of resistance was determined, in part, by the nature of the cells used to test the virus. The majority of ACV-resistant strains induced low or undetectable levels of HSV-specified thymidine kinase (TK), the enzyme responsible for phosphorylating ACV in infected cells. The TK-resistant strains were attenuated when injected into mice as indicated by reductions in virus replication, inflammation, and establishment of latent infections in sensory ganglia. The reduced virulence of the TK- strains was most marked after intracerebral inoculation, where the lethal dose was increased more than 100-fold compared with the parental isolates. However, one mutant is described which induced high levels of TK but was highly resistant to ACV and retained virulence for mice. PMID- 6247970 TI - Comparative activities of the oxa-beta-lactam LY127935, cefotaxime, cefoperazone, cefamandole, and ticarcillin against multiply resistant gram-negative bacilli. AB - A total of 91 multiply resistant bacterial strains, including Klebsiella pneumoniae (32 strains), Pseudomonas aeruginosa (16 strains), and Serratia marcescens (43 strains), were collected during hospital epidemics of nosocomial infection from 1975 to 1979. These strains were resistant to gentamicin, tobramycin, cephalothin, chloramphenicol, and ampicillin. Their susceptibility to three new broad-spectrum beta-lactams, LY127935 (a 1-oxa-beta-lactam), cefotaxime (HR 756), and cefoperazone (T 1551), was compared with the susceptibility of random strains of nine species of aerobic gram-negative bacilli collected in the same hospital in 1979. Susceptibility to cefamandole and ticarcillin was also determined. Strains of staphylococci and streptococci from that hospital and two nearby city-county hospitals were also compared for the three new cephalosporins and other effective antibiotics. The agar dilution method was used to measure the minimum inhibitory concentration for each antibiotic. The multiply resistant strains (minimum inhibitory concentration for gentamicin >/= 8 mug/ml) usually were as susceptible to the three new broad-spectrum beta-lactams as were non multiply resistant strains. Both Klebsiella pneumoniae and Serratia marcescens, including multiply resistant and non-multiply resistant strains, were most susceptible to the 1-oxa-beta-lactam LY127935 and cefotaxime. P. aeruginosa (both multiply resistant and non-multiply resistant strains) were most susceptible to cefoperazone. All three new beta-lactams were active against non-multiply resistant strains of Escherichia coli, Enterobacter spp., Proteus spp., and Citrobacter spp. Providencia stuartii were most susceptible to cefotaxime and the 1-oxa-beta-lactam LY127935. The three new beta-lactams were all less active against staphylococci (especially methicillin-resistant Staphylococcus aureus) than cephalothin. Streptococcus pyogenes and S. pneumoniae were very susceptible to cefotaxime and cefoperazone, though less susceptible to LY127935. None of the three new beta-lactams was active against S. faecalis. All were very active against both penicillinase-positive and -negative strains of Neisseria gonorrhoeae. PMID- 6247971 TI - Concentration of seeded simian rotavirus SA-11 from potable waters by using talc celite layers and hydroextraction. AB - There is mounting evidence for the waterborne transmission of diarrhea caused by rotaviruses. As a result, proper techniques are required for their recovery from samples of incriminated water. The combined efficiency of the talc-Celite technique and polyethylene glycol 6000 hydroextraction was, therefore, tested for this purpose, using Simian rotavirus SA-11 and MA-104 cells. Conditioning of the dechlorinated tap water samples was carried out by pH adjustment to 6.0 and the addition of Earle balanced salt solution to a final concentration of 1:100. Passage of a 1-liter volume of such a conditioned sample through a layer containing a mixture of talc (300 mg) and Celite 503 (100 mg) led to the adsorption of nearly 93% of the added SA-11 plaque-forming units. For the recovery of the layer-adsorbed virus, 3% beef extract and 1x tryptose phosphate broth were found to be superior to a variety of other eluents tested. When we tested 100-liter sample volumes, layers containing 1.2 g of talc and 0.4 g of Celite were employed. Virus elution was carried out with 100 ml of tryptose phosphate broth. The eluate was concentrated 10-fold by overnight (4 degrees C) hydroextraction with polyethylene glycol. With a total input virus of 7.0 x 10(5) and 1.4 x 10(2) plaque-forming units, the recoveries were about 71 and 59%, respectively. PMID- 6247972 TI - Reversal of radiation-dependent heat sensitization of Clostridium perfringens spores. AB - The effect of solute concentration on the sensitization of Clostridium perfringens spores to heat by ionizing radiation was investigated. As we have shown previously, spores of C. perfringens treated with gamma radiation are now sensitive to subsequent heat treatments than are spores that receive no radiation treatment. When gamma-irradiated spores were heated in the presence of increasing concentrations of glycerol or sucrose, the heat sensitivity induced by irradiation was progressively decreased. The magnitude of the increase in heat resistance induced by extracellular solutes was greater in gamma-irradiated spores than in nonirradiated spores. Based on these observations, it is proposed that the induction of heat sensitivity in spores by radiation is related to the loss of osmoregulatory or dehydrating mechanisms in irradiated spores. PMID- 6247973 TI - Effect of ionic environment on the inactivation of poliovirus in water by chlorine. AB - The rate of inactivation of poliovirus in water by chlorine is strongly influenced by the pH, which in turn influences the relative amounts of HOCl and OCl- that are present and acting on the virus in the region of pH 6 to 10. The distribution of HOCl and OCl- is influenced to a lesser extent by the addition of NaCl. The major part of the sharp increase in disinfection rate seen with this salt is thought to be due to its effect on the virus itself resulting in an increased chlorine sensitivity, especially at high pH. PMID- 6247974 TI - Relationships between environmental factors, bacterial indicators, and the occurrence of enteric viruses in estuarine sediments. AB - Current standards for evaluation of the public health safety of recreational and shellfish-harvesting waters are based upon bacteriological analysis, but do not include an evaluation of the number of viruses. The objective of this study was to determine the occurrence of enteric viruses in estuarine sediments and to find a relationship, if any, between the presence of viruses in seawater or sediment or both and various biological and physicochemical characteristics of the environment. Viruses were found in greater numbers in sediment than in overlying seawater on a volume basis. Several types of enteroviruses were isolated: coxsackievirus types A16, B1, and B5, echovirus type 1, and poliovirus type 2. On several occasions, viruses were isolated from sediments when overlying seawaters met bacteriological water quality standards for recreational use. Statistical analysis of the relationship between viruses in seawater or in sediment and other variables measured yielded only one significant association: the number of viruses in sediment was found to be positively correlated with the number of fecal coliforms in sediment. No other physical, chemical, or biological characteristic of seawater or sediment that was measured showed statistically significant association with viral numbers. No correlation was found between bacterial indicators and virus in the overlying waters. The data indicated that evaluation of the presence of bacteria and viruses in sediment may provide additional insight into long-term water quality conditions and that indicator bacteria in water are not reflective of the concentration of enteric viruses in marine waters. PMID- 6247975 TI - Simultaneous concentration of Salmonella and enterovirus from surface water by using micro-fiber glass filters. AB - A method using micro-fiber glass filters (8-micrometers porosity) at pH 3.5 was successfully used for simultaneous concentration of Salmonella and enterovirus from Meurthe River samples, collected 8 km south of Nancy, France. A concentration of 10-liter samples was indispensable and permitted recovery of several enterovirus and Salmonella serotypes in concentrations of 1.3 most probable number of cytopathogenic units per liter and 18 bacteria per liter, respectively. PMID- 6247976 TI - Evaluation of various soil water samplers for virological sampling. AB - Two commercially available soil water samplers and a ceramic sampler constructed in our laboratories were evaluated for their ability to recover viruses from both tap water and secondary sewage effluent. The ceramic sampler consistently gave the best recoveries of viruses from water samples. Soil columns containing ceramic samplers at various depths provide a simple method for studying virus transport through sewage-contaminated soils. PMID- 6247977 TI - Micro-organisms in outpatient infantile gastroenteritis. AB - This study reports the results of an examination of the stools of 58 infants with gastroenteritis who were seen as outpatients. The stools were examined by routine bacterial culture, and by electron microscopy for virus particles. The stools of a comparable control group of infants who had no gastrointestinal symptoms were also similarly examined. Enteropathogenic Escherichia coli, Salmonella sp., and rotaviruses, as well as other viruses, particularly adenoviruses and coronaviruses, were isolated. PMID- 6247978 TI - Peripheral insensitivity to thyroid hormones in a euthyroid girl with goitre. AB - A 9-year-old girl was euthyroid with a small goitre, exophthalmos, scaphocephalic skull, minor sketelal abnormalities, and raised serum thyroid hormone concentrations. Other members of the family did not have goitres and their thyroid hormone levels were normal. From age 3 years the patient was treated for Graves's disease, but after 4 years treatment was stopped because of enlargement of the goitre. Despite increased serum thyroxine (T4), free T4 (FT4), and triiodothyronine (T3), basal serum TSH, and the TSH response to thyrotropin releasing hormone (TRH) were normal. Pituitary refractoriness was present because full suppression of the TSH response to TRH was achieved only after daily administration of 500 micrograms thyroxine. Urinary excretion of hydroxyproline, and the activity of red cell glucose-6-phosphate dehydrogenase remained normal when excess T4 was administered, demonstrating the tissue resistance to thyroid hormones. Peripheral lymphocytes were found to have nuclear receptors for T3 with normal affinity, but the relatively low binding capacity indicated that the biochemical defect might be a deficiency of nuclear receptor protein. The findings in this patient differ somewhat from previously reported cases of peripheral resistance to thyroid hormones. PMID- 6247979 TI - Fetal thyroid hyperplasia, rhesus isoimmunisation, and amniography. AB - Thyroid hyperplasia was identified at necropsy in 16 of 70 cases of haemolytic disease of the newborn due to rhesus isoimmunisation dying in the years 1959--76. No hyperplasia was found in the thyroids from 140 nonrhesus-affected infants matched for date of birth, bodyweight and length, and gestation, or in cases of haemolytic disease born before 1966. All 16 infants with thyroid hyperplasia had received intrauterine transfusions and the iodine-containing contrast media used for preliminary amniography were the only goitrogenic factors identified. Lipiodol, first used in 1966, was considered to have the greatest effect. The 16 infants with hyperplastic thyroids were less mature and smaller than 22 infants with normal thyroids who had been similarly exposed to contrast media. The high incidence of hyperplasia may be due to immaturity of the adaptive mechanisms which allow most normal individuals to escape the goitrogenic effects of iodine compounds. PMID- 6247980 TI - Effect of vitamin A acid on cyclic nucleotides of cultured keratinocytes. AB - Primary cultures of guinea pig ear keratinocytes were treated with vitamin A acid at plating, or at 14 h or 14 days after plating. The intracellular content of the cyclic nucleotides cAMP and cGMP was determined by radioimmunoassay at intervals during a period of 50 h after treatment. When added at plating, vitamin A acid produced a wave of DNA synthesis and increase in DNA which was at maximum between 30 and 40 h after plating, and coincided with decreased cAMP levels. This may represent a subpopulation of keratinocytes in S phase. Treatment with vitamin A acid at 14 h or 14 days after plating resulted in an immediate but temporary fall in cAMP and cGMP, and a wave of thymidine uptake but no increase in DNA per dish. Thus, a single treatment with vitamin A acid is mitogenic only when applied at plating. At other times, it can cause changes in cyclic nucleotide content without any observable cell proliferation. PMID- 6247981 TI - [Histochemical and electron microscopical studies of histiocytoma (author's transl)]. AB - In histiocytomas the alkaline phosphatase technique reveals a surprising number of capillaries. The capillaries branch out from the center to the periphery of the histiocytoma and even the capillaries beneath the epidermis proliferate. The cellular elements outside the capillaries, however, are fibroblasts, histiocytes and mast cells, as is revealed by various histochemical and electron microscopical examinations. Histiocytomas of short duration differ from older histiocytomas in that the former contain fibroblasts similar to those found in healing wounds (C-fibroblasts). PMID- 6247982 TI - Effect of hydrocortisone-17-butyrate, hydrocortisone, and clobetasol-17 propionate on prolyl hydroxylase activity in human skin. PMID- 6247983 TI - Electromyographical neuromuscular synapse testing and neurological findings in workers exposed to organophosphorous pesticides. PMID- 6247985 TI - The role of vagotomy in pancreaticoduodenectomy. AB - In a series of 41 pancreatoduodenectomies the Whipple procedure was done in 27 patients and total pancreatoduodenectomy in 14 others with two postoperative deaths. Among 39 survivors, seven developed evidence of stomal ulcer 20 days to six years after operation; details of their courses are summarized. Proven stomal ulcer occurred in five of 14 patients who did not have concomitant vagotomy with pancreatoduodenectomy (36%). Each of these required vagotomy secondarily in management. When two patients with hematemesis in whom stomal ulcer was suspected but not proven are included, the incidence of stomal ulcer in nonvagotomized patients with pancreatoduodenectomy (7/14) is 50%. There were no stomal ulcers in patients with pancreatoduodenectomy who had concomitant vagotomy (0/25). It is logical to add the protective effects of vagotomy to pancreatoduodenectomy, especially when the disease process favors prolonged survival. PMID- 6247986 TI - Release of cyclic adenosine 3',5'-monophosphate in the coronary venous blood during an intracoronary infusion of adenosine. AB - The effect of adenosine on the release of cyclic adenosine 3',5'-monophosphate (cyclic AMP) in the coronary venous blood was examined in 30 anaesthetized intact dogs. Adenosine was infused into the left anterior descending coronary artery (LAD) at a rate of 150 nmol . min-1 and coronary venous blood was sampled in the great cardiac vein (GCV), near the outflow site of the veins accompanying the LAD. Significant coronary veno-arterial differences in cyclic AMP plasma level were observed before and during the infusion. The myocardial blood flow supplied by the LAD increased from 56 +/- 3 to 237 +/- 23 ml . min-1 per 100 g myocardium and the rate of cyclic AMP release in the venous blood near the origin of the GCV increased from 15.2 +/- 3.0 to 104.8 +/- 29.5 pmol . min-1 per 100 g myocardium. The adenosine-induced release of cyclic AMP did not result from an action of the substance on the platelets in the coronary circulation since adenosine concentration comparable to that achieved in the LAD did not modify the cyclic AMP plasma level of arterial blood in vitro. It is concluded that the released nucleotide originated essentially in cardiac structures, i.e. the myocardial and/or coronary cells. The results support in vitro studies suggesting that cyclic AMP is involved in the metabolic regulation of coronary blood flow by adenosine. PMID- 6247987 TI - Recurrent thrombocytopenia following idiopathic thrombocytopenic purpura. The importance of platelet-bound IgG in establishing cause. AB - A 20-year-old man experienced two separate thrombocytopenic illnesses. The first episode represented classic idiopathic thrombocytopenic purpura (ITP) and was associated with elevated platelet-bound IgG values. Adequate control of thrombocytopenia could not be obtained with prednisone therapy, and splenectomy produced a clinical remission. Four weeks after splenectomy, an acute febrile illness typical of cytomegalovirus (CMV) infection developed, and CMV grew grom a sample of the patient's blood. Thrombocytopenia recurred during the CMV infection but was not associated with elevated platelet-bound IgG levels. Since the second episode of thrombocytopenia was associated with normal amounts of platelet-bound IgG, it was not ascribed to relapse of the ITP, and the thrombocytopenia resolved rapidly, without specific therapy. There are various therapeutic implications of an accurate causative diagnosis of thrombocytopenia. PMID- 6247984 TI - Heberden oration 1979: human aberrations of purine metabolism and their significance for rheumatology. PMID- 6247988 TI - Cytomegalovirus vaccine. Specific humoral and cellular immune responses in human volunteers. AB - Four seronegative adult male volunteers were immunized with Towne strain cytomegalovirus (CMV) vaccine. The only reaction was transient pain and swelling at the inoculation site. Viral cultures were performed during the first 12 weeks after immunization, and CMV was not recovered from throat, urine, or peripheral blood mononuclear cells. Both CMV-specific humoral and cellular immunity developed within three weeks of vaccination. Whereas humoral antibody titers declined steadily with time, the cellular immune responses seemed biphasic. An early peak in lymphocyte proliferation to CMV antigen occurred three to six weeks after immunization. Responses then diminished but increased again six to ten months after immunization. This study in a small group of normal male volunteers indicated that CMV vaccine was safe and immunogenic. That CMV vaccine elicited CMV-specific humoral and cell-mediated immunity is important, because there is evidence that both are necessary for protection from CMV infections. PMID- 6247989 TI - Methyldopa. Mechanisms and treatment 25 years later. AB - Methyldopa, an adrenergic-inhibiting compound, has been used for over 25 years as a safe and effective antihypertensive agent. The postulated mechanisms for the antihypertensive action of this compound have been varied and parallel our broadening knowledge of the role of the adrenergic nervous system in controlling arterial pressure. This review outlines the mechanisms of adrenergic control of the circulation and how the proposed mechanisms of action of methyldopa (ie, dopa decarboxylation, false neurotransmission, inhibition of renin release, and stimulation of alpha receptor sites in the brain) seem to account for the depressor action of the drug. Physiologic effects as well as immunologic and other clinical effects are also discussed. PMID- 6247990 TI - Surgery in ovarian cancer. AB - Ovarian cancer has the highest mortality of the cancers of the female genital tract. The signs and symptoms of ovarian cancer are either nonexistent or nonspecific. Women who are to undergo exploratory laparotomy without a definite diagnosis should have ovarian cancer considered as part of the differential diagnosis. Therefore, it is important that each surgeon know the current concepts of surgery for ovarian cancer. Documenting true extent of disease in those cases with limited ovarian cancer prevents the need for reexploration before adjuvant therapy. In those cases of disseminated disease, an attempt at tumor reduction should be undertaken, as reduction of tumor aggregates to less than 1.6 cm in greatest diameter improves prognosis. Surgery is the mainstay of therapy for ovarian cancer. Optimal initial surgery prevents the need for reexploration. PMID- 6247991 TI - Nesidioblastosis in children. AB - Three cases in which seizure disorder was first noticed were examined in the last seven years; low fasting glucose and high serum insulin levels then led to the diagnosis of severe hypoglycemia secondary to nesidioblastosis. Hypoglycemic episodes were uncontrolled by frequent oral feedings and intravenous administration of dextrose, glucagon, and diazoxide. Within three weeks after diagnosis, all three patients underwent subtotal pancreatectomy; all three survived and have been followed-up for two to seven years. Two remain euglycemic and have no evidence of CNS damage. The third has occasional fasting hypoglycemia that is treated with diazoxide; he continues to have a seizure disorder and is mentally retarded. Neonatal hypoglycemia secondary to hyperinsulinism requires prompt recognition and aggressive treatment to avoid irreversible CNS damage. Subtotal pancreatectomy safely and effectively restores the euglycemic state. PMID- 6247992 TI - An improved method for the preparation of human fetal and adult hepatocytes. AB - A method to prepare isolated hepatocytes from the small amounts of liver or liver fragments obtained from the human fetus following therapeutic abortion in early pregnancy is described. The hepatocytes have been characterized by electron microscopy and by their ability to dealkylate the benzodiazepine drug prazepam. The preparation of hepatocytes from a liver sample obtained from a kidney transplant donor is described and discussed. PMID- 6247993 TI - Correlation of the colony-forming abilities of xeroderma pigmentosum fibroblasts with repair-specific DNA incision reactions catalyzed by cell-free extracts. AB - Several normal and XP group A fiblast cell lines were exposed to the weakly carcinogenic and toxic agent methyl methanesulfonate, and the differences in their abilities to form colonies were determined. The XP group A cell lines investigated exhibited higher sensitivity towards methyl methanesulfonate than normal cell lines. Correspondingly, cell-free extracts of the same XP cell lines differed from normal ones in cleaving methyl methane-sulfonate-treated double stranded DNA less rapidly. Since depurinated DNA was cleaved by XP and normal cell lines at equal rates, it was concluded that the differences observed with methylated DNA were due to a reaction preceding cleavage at apurinic sites. In control experiments using extracts from Chinese hamster ovary cells liberation of m3Ade was observed indicating the presence of 3-methyl-adenine DNA glycosylase activity. Furthermore, extracts from a normal fibroblast line liberated small amounts of m3Ade, whereas the one of a XP group A cell line was found to be less effective. The possible role of 3-methyl-adenine DNA glycosylase activity as a rate-limiting factor in the incision step has been discussed. PMID- 6247994 TI - The susceptibility of the sandfly Lutzomyia longipalpis (Lutz & Neiva), diptera, phlebotomidae, to laboratory infection with bluetongue virus. AB - Bluetongue virus multiplied in the sandfly Lutzomyia longipalpis after intrathoracic inoculation but not after oral ingestion of virus. The level of virus multiplication was lower than that observed in similar experiments with the North American vector of bluetongue, Culicoides variipennis. Inoculated sandflies did not transmit virus after 6 to 9 days incubation at 25 degrees C. It is unlikely that L. longipalpis would be important in the maintenance of bluetongue virus in the wild. PMID- 6247995 TI - Bluetongue virus hemagglutination and its inhibition by specific sera. AB - Bluetongue-virus (BTV) was found to agglutinate a variety of erythrocytes including sheep-, chicken-, guinea pig- and mouse-erythrocytes. Hemagglutination was inhibited specifically with type specific serum. A temperature dependence was only found for chicken erythrocytes, which showed a hemagglutination optimum at 37 degrees C. The hemagglutination was lost upon treatment of the virus with 0.4% trypsin as well as after treatment with 0.01 M KJO4. Heating of the virus preparation to 56 degrees C resulted in the loss of the HA-activity. Gelchromatographic studies indicated that the hemagglutinating capacity is associated with the complete virion. Whereas virulent strains of BTV hemagglutinate a number of different erythrocytes the avirulent type tested produced only a slight hemagglutination with sheep red blood cells. However, specific antiserum produced with the avirulent strain yielded strong hemagglutination inhibition (HI) with the corresponding virulent strain. Treatment of sera prior to their use in the HI proved necessary to remove nonspecific inhibitors. The efficiency of KJO4 in removing nonspecific inhibitors. The efficiency of KJO4 in removing nonspecific inhibitors indicates that carbohydrates represent the major group of nonspecific inhibitors. The data represented recommended the hemagglutination inhibition tests as a new method to identify the various BTV serotypes. PMID- 6247996 TI - Mitogenic effect of 12-0 tetradecanoyl phorbol 13-acetate on non-human primate mononuclear cells and in vitro interaction with Epstein-Barr virus transformation. AB - 12-0 tetradecanoyl phorbol 13-acetate (TPA), known to promote tumors in mice and also to enhance viral transformation as well as induction of viral antigens, was demonstrated to be mitogenic to peripheral blood mononuclear cells from rhesus monkeys and three species of marmosets. Even though mitogenic responses varied between species and within species, the mitogenic dose response due to TPA was comparable to the response of phytohemagglutinin (PHA-P). A significant synergistic effect of PHA-P and TPA on mononuclear cells from marmosets was evident when they were used together at optimal doses. TPA also increased the efficiency of in vitro transformation of marmoset lymphocytes by Epstein-Barr virus. PMID- 6247998 TI - Amyotrophic lateral sclerosis with antecedent poliomyelitis. AB - Histopathological and virological studies were performed on autopsy tissue from a 47-year-old man who had a history of acute poliomyelitis at age 15 years and died after a three-year course of amyotrophic lateral sclerosis (ALS). The poliovirus serologic tests suggested prior infection with poliovirus type 3 but no ongoing poliovirus infection. The CNS showed typical features of ALS with no inclusion bodies or inflammatory cells. Attempts to isolate poliovirus in the CNS were unsuccessful and results of immunofluorescence studies for poliovirus antigen were negative. Molecular hybridization experiments using a DNA copy of the complete poliovirus genome failed to demonstrate poliovirus-related RNA or DNA sequences in the CNS. These studies, using sensitive techniques, indicate that there was no evidence of the continuing presence of poliovirus in this patient with ALS and antecedent poliomyelitis. PMID- 6247997 TI - Ultrastructural development and persistence of guinea pig cytomegalovirus in duet cells of guinea pig submaxillary gland. AB - Salivary glands from Hartley guinea pigs were experimentally infected with guinea pig cytomegalovirus (GPCMV) and examined by light and electron microscopy at different time intervals. Characteristic intranuclear and intracytoplasmic viral inclusions were observed in duct cells of infected animals. Viral inclusion counts and infectivity titers in the salivary gland reached maximum levels by 3 to 4 weeks after infection; infectivity persisted, though at reduced levels, for at least 30 weeks. Electron microscopic examination of viral inclusions revealed several developmental events including nucleocapsid assembly, envelopment of nucleocapsids at the inner nuclear membrane and their enclosure by a thin vacuolar membrane. While contained within cytoplasmic vacuoles, enveloped virions acquired surface spikes. Cytoplasmic vacuoles containing virions subsequently coalesced and discharged mature virions at the cell surface into the lumen of the salivary gland duct. The data indicate that the ultrastructural development of GPCMV in the guinea pig salivary gland shows many similarities to that of human cytomegalovirus in humans. The salivary gland may provide a primary locus for virus shedding and horizontal transmission of cytomegalovirus. PMID- 6247999 TI - Multiple neurologic paraneoplastic syndromes: report of a case. PMID- 6248000 TI - Strawberry pickers' palsy. PMID- 6248001 TI - Human schwann cells in tissue culture: histochemical and ultrastructural studies. AB - Schwann cells cultures were established from 40 human peripheral nerves that underwent biopsy according to an explant-reexplantation technique that markedly reduces non-Schwann cells and achieves cultures greatly enriched in Schwann cells suitable for a wide range of studies. Described are the growth characteristics and histochemical, ultrastructural, and ultrastructural-cytochemical patterns of normal human cultured Schwann cells from 12 patients with demonstrable peripheral nerve abnormality. These findings serve as a basis of comparison when seeking abnormalities of Schwann cells grown from peripheral nerves of patients with putative dysschwannian neuropathies. PMID- 6248002 TI - Phenytoin and chlorpromazine in the treatment of spasticity. AB - The efficacy of phenytoin sodium and chlorpromazine hydrochloride in the reduction of spasticity was evaluated in both open and controlled studies. In each study, the majority of patients exhibited both objective and subjective signs of improvement. Reduction of motor tone in spastic muscles, as well as improvement in functiional status, was observed. Most patients experienced greater benefit from the combination of phenytoin and chlorpromazine than from either drug alone. The use of the drugs in combination permitted decreased chlorpromazine doses and reduced unwanted side effects such as lethargy and somnolence. These drugs may exert their action by suppressing fusimotor efferent as well as afferent discharged from muscle spindles. The results suggest that the fusimotor system is an important pharmacologic target in the treatment of spasticity. PMID- 6248003 TI - Perinatal neuropathy as an early manifestation of Krabbe's disease. AB - An asymptomatic child with antenatally diagnosed globoid cell leukodystrophy was found to have electrodiagnostic evidence of peripheral neuropathy at 7 weeks of age. The earliest prior such evidence in the literature was in a 6-month-old child. Thus, peripheral neuropathy can be both the initial manifestation and a very early finding in Krabbe's disease. PMID- 6248004 TI - Adrenoleukodystrophy. Report of two cases with relapsing and remitting courses. AB - Two boys with adrenoleukodystrophy (ALD) had unusual clinical courses. The first had three episodes of relapse and two remissions associated with elevation and fall in CSF protein levels. The second boy has had a prolonged remission of his neurologic symptoms with continuing adrenocortical failure. There may be a limited role for steroids in the treatment of the cerebral aspects of ALD. PMID- 6248005 TI - Adenoid cystic carcinoma of the lacrimal gland in a child. AB - An unusual case of adenoid cystic carcinoma of the lacrimal gland occurred in an 11-year-old child. Clinical, echographic, and histopathologic characteristics, as well as the management of this usually fatal disease, are discussed. The subtle signs and symptoms of this tumor were noted at the age of 9 years. A review of the literature reveals this to be the youngest patient in whom this tumor has been reported. PMID- 6248006 TI - Adenoid cystic carcinoma of the salivary gland. AB - We describe 15 patients with adenoid cystic carcinoma of the salivary glands treated by radiotherapy from 1960 to 1978. All patients were treated for localized disease either definitively or after surgical resection. The site of origin and local tumor extensions are reviewed and the results of treatment analyzed. Eighty-three percent of the tumors were controlled by combined treatment (surgery and postoperative radiotherapy) for one to ten years, 80% for more than five years. In the latter group, seven of ten patients had tumors with poor prognostic features. Eighteen patients treated by surgery alone have been reviewed for comparative five-year recurrence rates. This group and similar groups reported in the literature have higher recurrence rates at five years. Two patients treated definitively by radiotherapy have had tumor control for four years. This series and other reports demonstrate that adenoid cystic carcinoma is amenable to control by radiotherapy. Elective postoperative radiotherapy may assist in diminishing the high recurrence rates and improve survival. PMID- 6248007 TI - Adenoid cystic carcinoma of the nose, paranasal sinuses, and palate. AB - A retrospective study was performed on 18 cases of adenoid cystic carcinoma involving the nose, paranasal sinuses, or palate. The most common symptoms seen initially were referable to a mass or epistaxis. Surgery was the only form of therapy associated with long survival, although the addition of postoperative radiation therapy appears to prolong survival. All recurrences were first noted in the primary area. Factors that correlated best with surgical were clear surgical margins and absence of cranial nerve involvement. PMID- 6248008 TI - Pleomorphic adenoma manifesting as aural polyp. Report of a case. AB - We report the sixth known case of a pleomorphic adenoma of the external auditory canal. It manifested as an aural polyp, and the diagnosis was made only after microscopic pathologic examination. Complete removal was accomplished after a total parotidectomy (with preservation of the facial nerve) provided access to the parapharyngeal space surrounding the internal carotid artery, where it is postulated that the tumor originated. A thorough knowledge of the developmental anatomy of this area greatly enhances operative success. PMID- 6248009 TI - Cable grafting and irradiation. PMID- 6248010 TI - The influence of beta blockers upon plasma cyclic AMP levels. AB - Beta adrenoreceptor blocking drugs with high intrinsic sympathomimetic activity (pindolol and alprenolol) produced significant elevation of plasma cyclic AMP levels, when compared to propranolol. In hypertensive patients, despite these marked differences in plasma cyclic AMP levels, similar blood pressure control was achieved with these three beta blockers. PMID- 6248011 TI - Postrectal neoplasms and cysts. AB - The postrectal space is extensive and is in relationship to the sacral promontory and sacrum above and the coccyx below. Any of the structures in or adjacent to the space may be involved by or give rise to a postrectal neoplasm. In addition, a group of congenital neoplasms and cysts may also present in this space. Uhlig and Johnson in 1975 reviewed patients presenting to hospitals in the Portland, Oregon, U.S.A. area over a 25-year period. The population of Oregon in 1970 was 379,000. A total of 63 cases were reported. These tumours and cysts are an uncommon problem. PMID- 6248012 TI - Perianal Paget's disease: a case report. AB - A case of perianal Paget's disease is presented. The salient features of this disease include perianal irritation, a perianal rash, and usually, as in this patient, an associated underlying carcinoma. The disease is rare and has to be differentiated from malignant melanoma, Bowen's disease and transitional cell carcinoma. This patient was also remarkable since the associated malignancy was an equally rare carcinoma of anal gland origin. PMID- 6248013 TI - The beta-subunit of chorionic gonadotrophin as a tumour marker in gestational trophoblastic disease. AB - The clinical usefulness of the serum level of the beta subunit by radioimmunoassay was evaluated in 96 patients with gestational trophoblastic disease. The measurement of the hormone-specific beta subunit has allowed a better understanding of the activity of the various types of disease, with a correlation between the initial serum levels and the different subtypes of hydatidiform mole, and the ability to predict the development of malignant sequelae. The phenomenon of trophoblastic persistence after uterine evacuation was confirmed: although the half-life of the beta subunit was 4 days during the early phase, there was an average period of 8 weeks before levels fell to negative and 12 weeks was the limit for spontaneous regression. The serial beta subunit levels were found to provide an accurate indication of the clinical course of the disease in untreated and treated patients, and treatment could be withheld after 3 consecutive weekly negative values. PMID- 6248014 TI - Agricultural aviation medicine in the Soviet Union. AB - The Soviet Union has developed one of the world's most sophisticated civil aviation medicine programs. The program gives specific attention to aerial application operations and includes special preflight pilot medical examinations, aircraft with specialized protective airflow systems for the pilots, minimum flight altitude spraying limit of 5 m, and the use of a "chemical log book" by each pilot in addition to the flight log book. These and additional steps--i.e. limiting a pilot's daily agricultural flights to 4-6 h--have led to a reported USSR agricultural aviation annual accident rate near zero. The Soviet workhorse aircraft, the Antonov AN-2, can serve multipurpose roles since, when not used for application flights, it can be rapidly converted to executive, courier, cargo, or air taxi, or air ambulance use. A new, single-engine turbojet biplane, the Polish M-15, is undergoing evaluation in the Soviet Union as a replacement for the AN-2. Countries with very high agricultural aircraft accident rates may wish to study the Soviet approach, especially the use by the pilot of a chemical log book. PMID- 6248015 TI - Reduction of drinking-associated feeding by C-terminal octapeptide of cholecystokinin-pancreozymin. PMID- 6248016 TI - Prenatal exposure to cannabis: a critical review of effects on growth, development, and behavior. PMID- 6248017 TI - In vitro phosphorylation of a 41,000-MW protein band is selectively increased 24 hr after footshock or learning. PMID- 6248018 TI - Increased uracil nucleotide metabolism during the induction of cardiac hypertrophy by beta-stimulation in rats. AB - The dynamics of uracil nucleotides was followed in the rat heart during the induction of cardiac hypertrophy by beta-adrenoreceptor stimulation. Isoproterenol (ISO) 5 mg . kg-1 was administered subcutaneously daily for 8 consecutive days. A significant increase in ventricular dry weight (40%) was observed on the 5th day of beta-stimulation, thereafter no further increase occurred. A single dose of ISO increased uridine triphosphate (UTP) concentration and the whole uracil nucleotide pool (UN). The increase was maximal (80 and 100%) 12 hours after ISO administration. The 32phosphate incorporation into the alpha phosphate group of UN was increased by about a factor of 2 for the same period of time. Slight decrease in pool sizes (UTP and UN) and labelling occurred from 12 to 24 h after beta-stimulation. Similar changes also occurred on the 8th day of ISO administration, however modifications in concentrations and labeling were attenuated. The results show that modifications in the synthesis of UN should also be taken into account when studying the early events leading to cardiac hypertrophy. PMID- 6248019 TI - Investigations on glycerinated cardiac muscle fibres in relation to the problem of regulation of cardiac contractility--effects of Ca++ and c-AMP. AB - Alterations in myocardial contractile force and maximum unloaded shortening velocity (Vmax) occurring in the course of isometric twitch contraction and with changes in inotropism are assumed to be mediated by changes in intracellular Ca++ and/or c-AMP concentration. In the present study, the influences of Ca++ and cyclic AMP upon the contractility of briefly glycerinated myocardial preparations are described. It is shown that Ca2++ ions affect tension and Vmax, as measured by rectangular releases in length, in different concentration ranges. This suggests that, besides the number of attached crossbridges regulated by Ca++ binding to troponin C, a Ca++-dependent phosphorylation of the P-light chain of myocardial myosin may be involved in the regulation of Vmax. Cyclic AMP, on the other hand, induces phosphorylation of troponin I, thereby reducing the sensitivity of tension to Ca++. It is concluded that the positive inotropic effect of catecholamines may be mediated by the described actions of intracellular Ca++ and c-AMP upon the contractile structures where c-AMP dependent troponin phosphorylation could account for the acceleration of relaxation. PMID- 6248021 TI - [Occurrence of infectious pancreatic necrosis virus (IPN) in different fish species]. PMID- 6248020 TI - Subcellular changes during cardiac hypertrophy and heart failure due to bacterial endocarditis. PMID- 6248022 TI - [The efficacy of foot and mouth disease vaccines after long- term storage]. PMID- 6248023 TI - [The rotating aeration (system fuchs) for treatment of liquid animal and municipal wastes. 8. The effect of aerobic treatment of foot and mouth disease virus]. PMID- 6248024 TI - An adenosine triphosphate-dependent carbamoylphosphate--3-hydroxymethylcephem O carbamoyltransferase from Streptomyces clavuligerus. AB - Cell-free supernatants from cells of Streptomyces clavuligerus (N.R.R.L. 3585), which are actively synthesizing cephamycin C, transfer a carbamoyl group from carbamoylphosphate to a 3-hydroxymethylceph-3-em-4-carboxylic acid nucleus to form a 3-carbamoyloxymethylcephem. This reaction was stimulated by nucleoside triphosphates and by a mixture of Mn2+ and Mg2+ cations. The enzyme responsible was purified 40-fold by batch absorption onto DEAE-cellulose and hydroxyapatite. The purified O-carbamoyltransferase is most active at pH 6.8. It is stabilized by phosphate anions, but is inhibited by PPi anions, (NH4)2SO4 or NaCl. The enzyme is stimulated by ATP, but it is not known whether this nucleotide acts as an effector or as a substrate. Some activity is observed with dATP, but two other analogues of ATP, in which a methylene group replaced the oxygen atom between the alpha- and beta- or the beta- and gamma-phosphorus atoms, inhibit the action of ATP itself. The enzyme synthesizes a wide range of 3-carbamoyloxymethylcephems. The structure of some of these products, for example that of cefuroxime (3 carbamoyloxymethyl-7 beta-[2-(fur-2-yl)-2-syn-methoxyiminoacetamido]ceph-3-em-4 carboxylic acid), was confirmed by their proton-n.m.r. spectra. PMID- 6248025 TI - The isolation and preliminary characterization of N-acetyl-D-glucosamine kinase from rat kidney and liver. AB - 1. Procedures for the extensive purification in high yield of N-acetyl-D glucosamine kinase from rat liver and kidney are described. The separation of this enzyme from hepatic glucokinase depended primarily on their differing behaviour on an affinity column of Sepharose--N-(6-aminohexanoyl)-2-amino-2-deoxy D-glucopyranose. 2. This N-acetyl-D-glucosamine kinase also catalyses the phosphorylation of N-acetyl-D-mannosamine and, at a lower rate, several other sugar analogues, including D-glucose. 3. A comparison of the behaviour of the enzyme during gel filtration and electrophoresis in sodium dodecyl sulphate/polyacrylamide gels suggests that N-acetyl-D-glucosamine kinase is a symmetrical dimer of mol.wt. 80000. PMID- 6248026 TI - Kinetic characterization of N-acetyl-D-glucosamine kinase from rat liver and kidney. AB - 1. Under normal assay conditions the N-acetyl-D-glucosamine kinases from rat liver and kidney show a pH-dependent lag phase before reaching a steady state, which is probably due to reversible dissociation of the dimeric enzyme. 2. The enzyme catalyses the phosphorylation of N-acetyl-D-glucosamine, N-acetyl-D mannosamine and D-glucose at pH 7.5, with apparent Km values of 0.06, 0.95 and 600 mM respectively for the enzyme from liver and 0.04, 1.0 and 410 mM respectively for the kidney enzyme. It is strongly inhibited by ADP. 3. The interaction between the enzymes and acceptor substrates shows non-Michaelian kinetics with respect to N-acetyl-D-glucosamine but normal behaviour towards N acetyl-D-mannosamine and D-glucose. 4. Both N-acetyl-D-glucosamine and N-acetyl-D mannosamine inhibit the phosphorylation of D-glucose; this inhibition appears to be mixed in character. 5. The facts that the enzymes catalyse the phosphorylation of N-acetyl-D-mannosamine and D-glucose do not detract from the designation of the enzymes as N-acetyl-D-glucosamine kinase. Phosphorylation of glucose in vivo by these kinases is unlikely. PMID- 6248027 TI - The use of arginine analogues for investigating the functional organization of the arginine-binding site in lobster muscle arginine kinase. Role of the 'essential' thiol group. AB - 1. The nature of arginine binding to lobster arginine kinase and the extent of its possible involvement with the ;essential' thiol group of the enzyme has been investigated with some inhibitory analogues of arginine. 2. Most of the analogues inhibit competitively, although mixed inhibition may occur if the alpha-carboxy group or alpha-amino group is absent. 3. The K(i) values indicate that strength of binding depends on the length of the carbon chain (l-isoleucine>l-valine>l- alpha-aminobutyrate>l-alanine) and the integrity of the substituents on the alpha carbon atom (l-arginine>agmatine and l-ornithine>putrescine). The guanidino group probably contributes little to substrate binding, but a positive charge near the delta-nitrogen atom appears to be important (l-ornithine>l -citrulline>l-alpha aminobutyrate). A cyclic analogue, 2-carboxymethyl-3-oxo-2,3,5,6,7,8-hexahydro-1H imidazo [1,2-a][1,3]diazepine-8-carboxylic acid, has a low K(i) value similar to that of an equivalent straight-chain form, suggesting that arginine probably binds in a folded configuration. 4. The aliphatic l-amino acids give enzyme difference spectra similar to that with l-arginine and the integrity of the alpha carboxy and alpha-amino groups appears to be a minimal but not sufficient requirement for this, as l-ornithine gives an atypical difference spectrum. A difference spectrum is interpreted as indicating an enzyme conformational change. No difference spectrum was observed with methylguanidine. 5. The ability of aliphatic alpha-l-amino acids to protect against inhibition by 5,5'-dithiobis-(2 nitrobenzoic acid) is proportional to the number of atoms in the carbon chain and inversely proportional to K(i). Ornithine gives greater protection than citrulline; analogues lacking the alpha-amino groups also protect. Agmatine, lacking the alpha-carboxy group, did not protect. 6. It is concluded that it is unlikely that the ;essential' thiol group in the enzyme interacts with any part of the arginine molecule during catalysis except, possibly, the alpha-carboxyl group. PMID- 6248028 TI - A biochemical comparison of normal human liver and hepatocellular carcinoma ferritins. AB - 1. The iron contents, gel migration rates and isoelectric-focusing patterns of normal liver and hepatocellular carcinoma ferritins from the same patients were compared. 2. Sucrose-density-gradient centrifugation showed that the number of iron atoms per ferritin molecule was decreased to approximately half in carcinoma tissue when compared with normal liver. 3. On electrophoresis, hepatocellular carcinoma ferritin migrates faster and is therefore more negatively charged than normal liver ferritin, thus refuting the general view that the more negatively charged a ferritin molecule the greater its iron content. 4. Comparison of tumour and normal liver ferritin subunit compositions on acid/urea/polyacrylamide gels showed hepatocellular carcinoma ferritin to contain an additional, more negatively charged, subunit to normal liver ferritin. 5. Isoelectric focusing showed that hepatocellular carcinoma tissue contains isoferritins with isoelectric points intermediate between the ranges of normal liver and normal heart isoferritins. PMID- 6248029 TI - Properties of freshly purified and thiol-treated spinach chloroplast fructose bisphosphatase. AB - Freshly purified spinach chloroplast fructose bisphosphatase is powerfully inhibited by inorganic phosphate competitively with respect to its substrate fructose 1,6-bisphosphate. The concentrations of phosphate and substrate in the chloroplast stroma are such that the enzyme in this form could not operate at a significant rate in vivo. Incubation of the enzyme with dithiothreitol for 24 h decreases the Km for fructose 1,6-bisphosphate from 0.8 to 0.033 mM, decreases the Km for Mg2+ from 9 to 2 mM and substantially alleviates inhibition by inorganic phosphate. The physiological significance of thiol activation of the enzyme is discussed. PMID- 6248030 TI - Ubiquinones have surface-active properties suited to transport electrons and protons across membranes. AB - Surface-active properties of ubiquinones and ubiquinols have been investigated by monomolecular-film techniques. Stable monolayers are formed at an air/water interface by the fully oxidized and reduced forms of the coenzyme; collapse pressures and hence stability of the films tend to increase with decreasing length of the isoprenoid side chain and films of the reduced coenzymes are more stable than those of their oxidized counterparts. Ubiquinone with a side chain of two isoprenoid units does not form stable monolayers at the air/water interface. Mixed monolayers of ubiquinol-10 or ubiquinone-10 with 1,2-dimyristoyl phosphatidylcholine, soya phosphatidylcholine and diphosphatidylglycerol do not exhibit ideal mixing characteristics. At surface pressures less than the collapse pressure of pure ubiquinone-10 monolayers (approx. 12mN.m(-1)) the isoprenoid chain is located substantially within the region occupied by the fatty acyl residues of the phospholipids. With increasing surface pressure the ubiquinones and their fully reduced equivalents are progressively squeezed out from between the phospholipid molecules until, at a pressure of about 35mN.m(-1), the film has surface properties consistent with that of the pure phospholipid monolayer. This suggests that the ubiquinone(ol) forms a separate phase overlying the phospholipid monolayer. The implications of this energetically poised situation, where the quinone(ol) is just able to penetrate the phospholipid film, are considered in terms of the function of ubiquinone(ol) as electron and proton carriers of energy-transducing membranes. PMID- 6248031 TI - Influence of the position of the double bond in steroid substrates on the efficiency of the proton-transfer reaction by Pseudomonas testosteroni 3-oxo steroid delta 4-delta 5-isomerase. AB - Studies of the proton-transfer reaction by Pseudomonas testosteroni 3-oxo steroid Delta(4)-Delta(5)-isomerase with Delta(5(6))- and Delta(5(10))-steroid substrates demonstrate the importance of the position of the double bond for the efficiency of the isomerization process. Thus 3-oxo-Delta(5(6))-substrates have markedly high k(cat.) values, whereas those of 3-oxo-Delta(5(10))-substrates are very low and their apparent K(m) values approach equilibrium dissociation constants. The first step in the isomerization process is: [Formula: see text] which is governed by the k(-1)/k(+1) ratio and is shown to be very similar for the two classes of substrates (3-oxo-Delta(5(6))- and -Delta(5(10))-steroids). They therefore differ in the steps distal to the initial formation of the Michaelis-Menten complex. The use of the deuterated androst-5(6)-ene-3,17-dione substrate enabled us to calculate individual rate constants k(+1) and k(-1) as well as to determine the apparent rate-limiting step in the isomerization process. With the deuterated oestr-5(10)-ene-3,17-dione substrate, no significant isotope effect was observed suggesting that a different rate-limiting step may be operative in this isomerization process. Data are presented that indicate that under optimal concentrations of the efficient androst-5(6)-ene-3,17-dione substrate, the forward reaction for ES complex formation (as defined by k(+1)) is limited only by diffusion and the apparent K(m) does not approach the equilibrium constant, suggesting that the evolution of this enzyme has proceeded close to ;catalytic perfection'. PMID- 6248032 TI - Enzymic hydrolysis of sphingomyelin in the presence of bile salts. AB - Sphingomyelin in mixed dispersion with bile salts was hydrolysed by the solubilized sphingomyelinase of rat brain lysosomes. In parallel studies, physical properties of these dispersions were determined. The kinetic curves that described the rate of hydrolysis as a function of increasing concentrations of bile salt were multiphasic. A region of very low activity was followed by an ascending portion, a peak, a descending portion, a trough and a second ascending portion. The positions of the initiation points, peaks and troughs were found to be a function of the respective ratios of the bile salt to sphingomyelin for the detergent sodium taurodeoxycholate, but of the absolute concentration of the detergent for sodium taurocholate. Turbidity studies suggested that hydrolysis of sphingomyelin begins at a bile salt concentration that solubilizes the lipid and incorporates it into a mixed micelle with the detergent. Ultracentrifugation studies suggested that the sizes of the mixed aggregates of detergent and lipid were a function of the ratio of taurodeoxycholate to sphingomyelin, but of the absolute concentration of the bile salt, for sodium taurocholate. PMID- 6248033 TI - The preparation of calmodulins from barley (Hordeum sp.) and basidiomycete fungi. AB - 1. Calmodulin-like proteins were purified from the fruiting bodies of higher (basidiomycete) fungi and barley (Hordeum sp.) shoots. 2. These calmodulins have electrophoretic mobilities on 10% (w/v) polyacrylamide gels at pH 8.3 in the presence of 6 M-urea and at pH 8.3 in the presence of 0.1% sodium dodecyl sulphate similar to that of bovine brain calmodulin. They interacted with rabbit skeletal-muscle troponin I in the presence of Ca2+. 3. Barley and fungal calmodulins activated myosin light-chain kinase and phosphodiesterase in the presence of Ca2+, although the amounts needed were at least an order of magnitude greater than is required to produce the same effect with mammalian calmodulin. 4. Amino acid analyses indicated a number of differences from the mammalian protein, most notably the absence of trimethyl-lysine. 5. By using 125I-labelled calmodulin, a small amount of calmodulin-binding protein was detected in homogenates of barley and fungi. 6. No protein corresponding to calmodulin could be found in Escherichia coli or yeast, although a relatively high concentration of a protein that bound calmodulin was detected in E. coli by this technique. PMID- 6248034 TI - Rapid type 2 molybdenum(V) electron-paramagnetic resonance signals from xanthine oxidase and the structure of the active centre of the enzyme. AB - Rapid type 2 molybdenum(V) e.p.r. signals from reduced functional xanthine oxidase have been further investigated. These signals, which show strong coupling of two protons to molybdenum, have been obtained under a variety of new conditions: specifically either at pH 8.2 in the presence of borate ions, or at pH 10.1--10.7 with or without various other additions. Parameters of the signals were obtained with the help of computer simulations. In at least some of these signals, the coupled protons must be located on the enzyme rather than on bound species. The relationship between type 1 and type 2 Rapid signals is discussed. They may represent geometrical isomers, or alternatively, hydroxyl uptake as a ligand of molybdenum may be involved in formation of type 2 species. PMID- 6248035 TI - Novel inhibitors of poly(ADP-ribose) synthetase. AB - In a search for new inhibitors of the nuclear enzyme poly(ADP-ribose) synthetase, it was found that various benzamides substituted in the 3-position were the most inhibitory compounds found to date. Two of the benzamides, 3-aminobenzamide and 3 methoxybenzamide, were found to be competitive inhibitors, with Ki values or less than 2 microM. PMID- 6248036 TI - Poly(ADP-ribose) polymerase from Ehrlich ascites-tumour cells. Amino acid composition, N-terminal analysis and chemical cleavage of the purified protein. AB - Poly(ADP-ribose) polymerase was purified from Ehrlich ascites-tumour cells by two novel methods. Analysis for amino acid composition revealed a high percentage of acidic amino acids or their amides, and of basic amino acids. N-Terminal analysis with dansyl chloride revealed no terminal amino acid, indicating a blocked N terminal amino group. Analysis by gel electrophoresis of protein treated with 3 bromo-3-methyl-2-[(2-nitrophenylthio)-3H-indole, under conditions where selective cleavage of the polypeptide chain at tryptophan residues is obtained, showed six major peptide bands. PMID- 6248037 TI - Organization of thiol groups of electric-eel electric-organ sodium-plus-potassium ion-stimulated adenosine triphosphatase studied with bifunctional reagents. AB - The reactions of three bifunctional thiol-blocking reagents of differing cross linking spans and two monofunctional thiol-blocking reagents with the Na+ + K+ stimulated ATPase of the electric-eel electric organ were examined. 1,5-Difluoro 2,4-dinitrobenzene with a cross-linking span of 0.3--0.5 nm (3--5 A) and high solubility in non-polar solvent was the most efficient inhibitor of enzyme activity; thus essential thiol groups exist in a non-polar environment and are approx. 0.3--0.5 nm (3--5 A) from their nearest thiol-group neighbours. Ligands promoting phosphorylation of the Na+ + K+-stimulated ATPase decreased the number of thiol groups bridged by 1,5-difluoro-2,4-dinitrobenzene and by 4,4'-difluoro 3,3'-dinitrodiphenyl sulphone [0.7--1.0 nm (7--10 A) span]. Phosphorylation is associated with a conformational change in the enzyme. PMID- 6248038 TI - Decreased pyridoxal phosphate and kinase levels in iron-deficient rat liver. PMID- 6248039 TI - Interaction of protease inhibitors with the catalytic subunit of cAMP-dependent protein kinase. PMID- 6248040 TI - Light-triggered proton movements in retinal discs from the frog. PMID- 6248041 TI - In vitro and in vivo inhibition of rat liver cathepsin L by epidermal proteinase inhibitor. PMID- 6248042 TI - Na+,K+-ATPase: half-of-the-subunits cross-linking reactivity suggests an oligomeric structure containing a minimum of four catalytic subunits. PMID- 6248043 TI - Rotational motion of cytochrome c oxidase in phospholipid vesicles. PMID- 6248044 TI - A new protein factor functional in the ferredoxin-independent light activation of chloroplast fructose 1,6-bisphosphatase. PMID- 6248045 TI - Purification of a serum DNA binding protein (64DP) with a molecular weight of 64,000 and its diagnostic significance in malignant diseases. PMID- 6248046 TI - Effect of substrate and AMP on the reversal of Zn2+ inhibition of turkey liver fructose-1,6-bidphosphatase by chelators. PMID- 6248047 TI - Unusual spin-state transitions in the reduction of ferrylmyoglobin at low temperature. PMID- 6248048 TI - Production of both interstitial and basement membrane procollagens by fibroblastic WI-38 cells from human embryonic lung. PMID- 6248049 TI - Early rise in cyclic GMP after 1,25-dihydroxycholecalciferol administration in the chick intestinal mucosa. PMID- 6248050 TI - Oxidation-reduction potential of cytochrome C oxidase in mitochondria of yeast grown under various copper concentrations. PMID- 6248051 TI - Excitation of indole acetate in myeloperoxidase-H2O2 system: possible formation of indole acetate cation radical. PMID- 6248052 TI - Molecular motion in phospholipid bilayers in the gel phase: spin label saturation transfer ESR studies. PMID- 6248053 TI - Identification of cAMP binding proteins associated with the plasma membrane of the yeast Saccharomyces cerevisiae. PMID- 6248054 TI - Selective inhibition of macromolecular synthesis in transformed mouse cells by means of ATP-treatment. PMID- 6248055 TI - Existence of gamma-melanotropin (gamma-MSH)-like immunoreactivity in bovine and human pituitary glands. PMID- 6248056 TI - Histidyl-proline diketopiperazine, an endogenous brain peptide that inhibits (Na+ + K+)-ATPase. PMID- 6248058 TI - Deficiency of carnitine palmitoyltransferase in transformed lymphoblasts from a patient having a deficiency of carnitine palmitoyltransferase in skeletal muscle. PMID- 6248057 TI - Orientation of the NADPH dependent superoxide generating oxidoreductase on the outer membrane of human PMN's. PMID- 6248059 TI - Regulatory aspects of the cyclic AMP receptor protein in Escherichia coli K-12. PMID- 6248060 TI - Localization of 25-hydroxyvitamin D3-1 alpha-hydroxylase activity in the mammalian kidney. PMID- 6248061 TI - Evidence for a nucleation step in a lipid-protein interaction-kinetics of the incorporation of polymyxin into phosphatidic acid bilayer vesicles. PMID- 6248062 TI - Compound I of myeloperoxidase. PMID- 6248063 TI - Conditions for optimal electron transfer activity of cytochrome c oxidase isolated from beef heart mitochondria. PMID- 6248064 TI - The synthesis of beta-adrenergic receptors in cultured human lung cells: induction by glucocorticoids. PMID- 6248065 TI - Evidence for a temperature-dependent and temperature-independent pathway in the generation of complement-mediated transmembrane channels. PMID- 6248066 TI - Identification of a major human serum DNA-binding protein as beta 1H of the alternative pathway of complement activation. PMID- 6248067 TI - Chick embryo cells rendered respiration-deficient by chloramphenicol and ethidium bromide are auxotrophic for pyrimidines. PMID- 6248068 TI - Binding energy and the activation of hormone receptors. PMID- 6248069 TI - Characterization and localization of catecholamine-susceptible Na-K ATPase activity of rat striatum: studies using catecholamine receptor (ant)agonists and lesion techniques. PMID- 6248070 TI - In vitro effects of lithium chloride on ATPases of rabbit cerebral synaptic membranes. PMID- 6248071 TI - Specific inhibition of receptors for angiotensin II and angiotensin III in adrenal glomerulosa. PMID- 6248072 TI - beta-Diethylaminoethyldiphenylpropylacetate (SKF 525-A) and 2,4-dichloro-6 phenylphenoxyethylamine.HBr (DPEA) inhibition of fatty acid conjugation to 11 hydroxy-delta 9-tetrahydrocannabinol by the rat liver microsomal system. PMID- 6248073 TI - Prereplicative error-free DNA repair. PMID- 6248075 TI - Altered regulation of Epstein-Barr virus induced lymphoblast proliferation in rheumatoid arthritis lymphoid cells. PMID- 6248074 TI - Identification with potassium and vanadate of two classes of specific ouabain binding sites in a (Na+ + K+) ATPase preparation from the guinea-pig heart. PMID- 6248076 TI - Synthesis of 2 beta,16 beta-bis-(4'-dimethyl-1'-piperazino)-3 alpha,17 beta diacetoxy-5 alpha-androstane dibromide and related compounds. AB - A series of bisquaternary ammonio steroids having androstane skeletons have been prepared some of which possessed high neuromuscular blocking activity. One of the series 2 beta,16 beta-bis-(4'-dimethyl-1'-piperazino)-3 alpha, 17 beta-diacetoxy 5 alpha-androstane-dibromide (9, pipercurium bromide, Arduan) has proved to be a clinically useful agent of medium duration of action without side effects. The preparation of these ammonio steroids and structure-activity relationships within the series are described. The structure of 9 and related compounds was elucidated by spectrometric methods IR, NMR and MS. PMID- 6248077 TI - On some properties of a new steroid curare-like compound pipecurium bromide. AB - In experiments on cats it has been shown that 2 beta, 16 beta-bis (4'-dimethyl-1' piperazino)-3 alpha, 17 beta-diacetoxy-5 alpha-androstane dibromide (pipecurium bromide, RGH-1106, Arduan), is a non-depolarizing muscular blocker. The order of myorelaxation evoked by this agent is characteristic: first the chewing and limb muscles, then abdominal muscles and diaphragm and at the end intercostal muscles are relaxed. Pipercurium bromide has no cardiotropic, atropine-like, or ganglion blocking activity. It fails to influence the coronary blood-supply or myocardial oxygen consumption. No acetylcholinesterase inhibiting action of the compound was seen. It does not affect the central nervous system. PMID- 6248078 TI - Respiration paralysing and circulatory effects of a new non-depolarizing relaxant, pipecurium bromide, in anaesthetized dogs. AB - The effect of a new sterane-structure, non-depolarizing muscle relaxant 2 beta,16 beta-bis(4'-dimethyl-1'-piperazino)-3 alpha,17 beta-diacetoxy-5 alpha-androstane dibromide (pipecurium bromide, RGH-1106, Arduan) was studied in 42 mongrel dogs under general anaesthesia (ether, halothane, methoxyflurane, thiobutobarbital, hydroxydione and dehydrobenzperidol-fentanyl (NLA II). Onset and duration of action and the presence of circulatory side effects were examined. It was found that the mean onset of respiration paralysing action was 156.1 s and apnea lasted for 38 min. In the thiobutobarbital group apnea lasted for 74 min. Arterial systolic blood pressure and central venous pressure did not change, but the heart rate was mildly decreased by pipecurium bromide. ECG intervals (PQ, QT and TP) did not change considerably, and the variations ran parallel with the prolongation of RR intervals due to the decrease of heart rate. Pipercurium bromide is a non-depolarizing muscle relaxant of medium duration, without any significant circulatory effects. Its duration of action was prolonged in the presence of thiobutobarbital, indicating a drug interaction between the two preparations. PMID- 6248079 TI - The effect of the steroid muscle relaxant pipecurium bromide on the acetylcholinesterase activity of red blood cells in vitro. AB - The acetylcholinesterase (AchE) inhibitory effect of a muscle relaxant 2 beta,16 beta-bis-(4'-dimethyl-1'-piperazino)-3 alpha,17 beta-diacetoxy-5 alpha-androstane dibromide (pipecurium bromide, RGH-1106, Arduan), was studied in vitro. The inhibition of AchE activity of human red blood cells, expressed as pI50, was 3.99, whereas that of serum cholinesterase (ChE) was 4.33. The AchE inhibitor action was reversible. The inhibition was not influenced by the combined administration of promethazine or atropine. The combined effect of pipecurium bromide and of some other diamino-azasteroid agent proved to be additive. Pipecurium bromide showed mixed-type inhibitory effect both on AchE and ChE. PMID- 6248080 TI - Disposition of pipecurium bromide in rats. AB - The disposition of 2 beta,16 beta-bis-(4'-dimethyl-1'-piperazino)-3 alpha,17 beta diacetoxy-5 alpha-androstane dibromide (pipecurium bromide, RGH-1106, Arduan), a new neuromuscular blocking agent, was studied in rats by using labelled substance. Radioactive substance is rapidly taken up by the liver and to a lesser extent by the kidneys. The compound is retained by the liver for a longer period of time, some 6% of the administered 14C-activity can be recovered from the liver 21 days after the i.v. administration of the drug. Only traces of radioactivity could be detected in the brain and less than 0.1% of the dose could be found in the foetus. Binding to rat plasma protein is of about 30%. The compound seems to be eliminated with urine, the excreted amount being 37.55 +/- 11.91% and 45.44 +/ 17.29% during 24 and 48 h, respectively. No radioactivity was detected in the expired air. PMID- 6248081 TI - Pharmacokinetics of pipecurium bromide in the rat. PMID- 6248082 TI - Summary of safety tests with pipecurium bromide, a new neuromuscular blocking agent. AB - Acute toxicity studies with 2 beta,16 beta-bis(4'-dimethyl-1'-piperazino)-3 alpha,17 beta-diacetoxy-5 alpha-androstane dibromide (pipecurium bromide, RGH 1106, Arduan), a new neuromuscular blocking agent, revealed an order of sensitivity as follows: rabbits greater than mice greater than rats. Subchronic toxicity was tested on conscious dogs by 20 daily doses of 150 microgram/kg i.v. corresponding to 4-fold the planned clinical dose followed by daily intubation and artificial ventilation until recovery of spontaneous respiration. Dosage was limited by prolonged paralysis time requiring artificial ventilation. Apart from daily stress of paralysis preceding intubation no irreversible toxic changes were detected by laboratory and morphological tests. ECG changes were restricted to paralysis time, they were characterized by transitory arrhythmia and variation of the ST-segment. In additional studies on conscious and unconscious dogs no lethal ECG changes could be induced with cumulative dose totalling 10 mg/kg i.v. Short term in vivo and in vitro mutagen tests did not reveal either mutagenic and clastogenic effects or increase of chromosomal aberrations. Intravenous local tolerance in rats was satisfactory. PMID- 6248083 TI - First clinical experience with a new neuromuscular blocker pipecurium bromide. AB - The clinical trial of the new non-depolarizing muscle relaxant 2 beta,16 beta-bis (4'-dimethyl-1'-piperazino)-3 alpha,17 beta diacetoxy-5 alpha-androstane dibromide (pipecurium bromide, RGH-1106, Arduan) was performed on 80 patients who had to undergo medium and major size intraabdominal operation on the basis of chronic surgical indication. Four types of general anaesthetic methods were applied, neuroleptanalgesia, halothane, halothane-fentanyl combination and hydroxydione. The clinical applicability of pipecurium bromide was tried to establish the dose needed for complete muscle relaxation initially and repeatedly and the effect of antagonist drugs on the muscle relaxation. We investigated the duration of the first and repeated dose of the relaxant. Heart rate and arterial blood pressure were measured, mean arterial pressure and pulse pressure were calculated. In 10 patients of the halothane group the behaviour of some haemodynamic parameters was investigated. The changes of acid base parameters, blood gases, serum electrolytes and blood sugar were also observed. The administered doses were initially 3.88 mg/h, repeated doses 2.32 mg/h, this means 0.052 mg/kg body weight initially and 0.026 mg/kg body weight repeatedly The duration of effect after the first dose was 53 min, after the repeated doses 45 min. There were no direct effects on heart rate and arterial blood pressure. It did not affect myocardial contractility or work function, there was no remarkable changes in cardiac output. There were no direct metabolic changes due to pipecurium bromide. The relaxant has no histamine releasing effect. At the end of the anaesthesia the effect can be antagonized with neostigmine. During our observations there were no side effects or allergic reactions caused by pipecurium bromide. PMID- 6248084 TI - Report on clinical test of pipecurium bromide. AB - The actions of the new depolarization-blocking muscle relaxant agent; 2 beta,16 beta-bis-(4'-dimethyl-1'-piperazino)-3 alpha,17 beta-diacetoxy-5 alpha-androstane dibromide (pipecurium bromide, RGH-1106, Arduan), were studied in fentanyl-N2O, in halothane-N2O and in methoxy-flurane-N2O anaesthesia in a total of 94 patients. The drug in a dose of 0.05 mg/kg body weight (recommended by the manufacturer), elicited complete muscle relaxation, which was satisfactory even for performing abdominal operations. The effect occurred within 3-4 min, and subsided after 40-50 min. The residual effect had to be antagonized in 82% of the cases, and neostigmine had a satisfactory antagonizing effect in all patients. Transient fall of blood pressure and bradycardia (in 40.4% of the cases) were observed as side effects. Further studies are needed for the determination of the pathomechanism of bradycardia and to judge to what extent the inhalation anaesthetic agents influence the duration of action of pipecurium bromide. PMID- 6248085 TI - Clinical experience with a new steroid muscle relaxant: pipecurium bromide. AB - Experience gained in applying to 102 surgery patients a steroid muscle relaxant 2 beta,16 beta-bis-(4'-dimethyl-1'-piperazino)-3 alpha,17 beta-diacetoxy-5 alpha androstane dibromide (pipecurium bromide, RGH 1106, Arduan) is reported. Pipercurium bromide proved to be a potent muscle relaxant with a medium duration of action. It can successfully be applied for intubation. Residual relaxation can be antagonized with neostigmine. Pipecurium bromide did not influence circulation, is free of side effects and can be applied in anaesthesiologically high-risk patients. PMID- 6248086 TI - Circulatory effects of pipecurium bromide during anaesthesia of patients with severe valvular and ischaemic heart diseases. AB - Circulatory effects of 2 beta,16 beta-bis-(4.-dimethyl-1'-piperazino)-3 alpha,17 beta-diacetoxy-5 alpha-androstane dibromide (pipecurium bromide, RGH-1106, Arduan) were investigated in severe cardiac patients during the induction of anaesthesia, in the course of nitrous oxide-oxygen anaesthesia and during extracorporeal circulation. In a dose of 0.05 mg . kg-1 the drug did not cause significant changes in any of the circulatory parameters studied. It is a safe muscle relaxant which can be used in patients with valvular and ischaemic heart diseases as well. PMID- 6248087 TI - Comparative clinical study of pipecurium bromide and pancuronium bromide. AB - The properties and the effects of a new steroid muscle relaxant preparation 2 beta,16 beta-bis(4'-dimethyl-1'-piperazino)-3 alpha,17 beta-diacetoxy-5 alpha androstane dibromide (pipecurium bromide, RGH-1106, Arduan) were compared to those of pancuronium bromide in a controlled randomized clinicopharmacological study using ataranalgesic anaesthesiological technique. In 45 cases pipecurium bromide, in other 45 cases pancuronium bromide was used as long-acting muscle relaxant in anaesthesia for general surgical procedures. According to the results, pipecurium bromide is approximately 20% more potent than pancuronium bromide, it induces mechanical response characteristic for non-depolarizing muscle relaxants, and the residual neuromuscular blockade can be antagonized completely by neostigmine. There were no ECG alterations or specific serum enzyme (CPK, GOT. LDH) level changes observed. Pipecurium bromide did not influence blood pressure but in contrast to the heart rate increasing effect of pancuronium bromide, it caused mild bradycardia. On the basis of the study the drug can be used for further wide scale clinical investigations. PMID- 6248088 TI - Restriction endonucleases or the site-specific DNA endonucleases. AB - Our present view of the site-specific endonucleases, which appear to be ubiquituous in the prokaryote kingdom, is probably heavily distorted by our search for tools for recombinant DNA technology. Only those enzymes having recognition sequences in the range of three to seven specific bases have been isolated. Of course the usefulness of these enzymes in the analysis of complex genomes, the rise of "reverse genetics", and the immediate breakthroughs in the area of gene expression in eukaryotes, particularly the understanding of tumour virus RNA processing and gene rearrangements in the expression of immunoglobulin genes has dominated the consciousness of the molecular and cell biologists during the last five years. There is a great diversity of staggering, symmetry, asymmetry and degeneration in the recognition sequences found. Taking into account also the genetic data on site-specific recombination and/or DNA degradation suggests that our present collection of endonucleases may only represent a narrow spectrum of specificities on an open-ended scale of complexity. The enzymes, themselves provide a rich pool to be exploited by the biophysicist and the biochemist to probe the subtleties of DNA-protein interaction. PMID- 6248089 TI - Viruses as tools for studies on the molecular biology of mammalian cells. AB - 1. Multiple copies of intact adenovirus type 12 (Ad12) DNA are integrated into the DNA of Ad12-transformed hamster and Ad12-induced rat brain tumor cells. Free viral DNA is not present in the Ad12-transformed lines investigated. 2. Only few sites of integration are found in Al2-transformed hamster and Ad12-induced rat brain tumor cells. Integration may have occurred into repetitive cellular sequences at selective sites. These sites may be different in different cell lines, however, none of these sites has been analyzed in sufficient detail. 3. Three lines of Ad12-induced rat brain tumor cells exhibit identical patterns of integration. These lines have been derived from three brain tumors in one animal and may have evolved from the same transformed cell. 4. In Ad12-induced rat brain tumor cells early and late segments of the viral genome are expressed as polysome associated messenger RNA. 5. In human cells productively infected with adenovirus type 2 (Ad2), a large number of viral genome copies are linked to cellular DNA early postinfection. There are only a few sites of recombination (illegitimate?) which probably lie in repetitive cellular DNA sequences. The functional significance of this frequent recombination is unknown. PMID- 6248091 TI - [Determination of proteins with the Coomassie brilliant blue G 250 method. III. Behavior of various pure proteins and comparative analysis with the biuret and Lowry methods]. AB - Some proteins were tested by the Bradford's method with Coomassie Brilliant Blue G 250. The findings were compared to those obtained by the Lowry's and the biuret methods. Coomassie, as the other methods, has the inconvenient of giving different absorbaces according to the nature of single protein. The use of standards of analogous composition in assaying proteins by the Bradford's method is suggested. PMID- 6248090 TI - [Preparation of samples of biological fluids for electron spin resonance (ESR) examination]. AB - The ESR (Electron Spin Resonance) Technique, is usually used in the study of Free Radicals and Metal - Proteins, in biological fluids, but the most apt method for the preparation of the sample has still to be defined. In this work the A.A. describe and analyse the negative and positive aspects of several methods. The results of the E.S.R. spectra, obtained by means of lyophilization, that is the most used method in literature, have been compared with those obtained by means of concentration of some biological fluid (serum and synovial fluid). The A.A. demonstrated that the lyophilization does not permit the reproducibility of the spectra, for different spectra are obtained from the same lyophilized serum and synovial fluid samples. A high reproducibility of the spectra is instead obtained by the concentration of the sample means of the "collodion bag" or "Aquacide" methods. The A.A. are convinced that for on exact investigation of the E.S.R. Signals, only the concentration method is useful, and not the lyophilization method as reported in literature. PMID- 6248092 TI - Elevated levels of prostaglandin E2 in Yoshida hepatoma and the inhibition of tumour growth by non-steroidal anti-inflammatory drugs. AB - Prostaglandin (PG) E2 biosynthesis in Yoshida hepatoma (AH 130) was evaluated by radioimmunoassay. When hepatoma cells were incubated in vitro, the levels of PGE2 in the medium were similar to those found in hepatocytes for the first 2 h; this was followed by a rapid increase in PGE2 formation, and the 6h incubation levels were 4-fold higher than in hepatocytes. Addition of sodium arachidonate markedly and dose-dependently stimulated PGE2 synthesis; the increase was largely prevented by the addition of indomethacin (1 microM) or L 8027, a prostaglandin synthetase inhibitor. Experiments in vivo indicated that indomethacin treatment of tumour-bearing rats significantly reduced the tumour mass. When rats were injected with PGE2 after receiving the drug, the number of tumour cells was very similar to that of untreated animals. This, as well as the inhibition of tumour growth by acetylsalicylic acid, strongly suggests that the inhibition of PG biosynthesis by anti-inflammatory drugs and the inhibition of tumour proliferation may be closely associated events. It was also found that injections of indomethacin very significantly prolonged survival of hepatoma-bearing rats. Since PGE2 does not appear to affect the cyclic AMP levels of hepatoma cells, it is possible that hepatoma may use PGE2 to subvert the immune system. This could help to explain the effectiveness of anti-inflammatory drugs in the control of tumour growth. PMID- 6248093 TI - Electron spin resonance studies on caeruloplasmin and iron transferrin in patients with chronic lymphocytic leukaemia. AB - Whole-blood caeruloplasmin measured by electron spin resonance was studied in 41 patients with chronic lymphocytic leukaemia. The levels were above normal at all stages of the disease, rose with increasing clinical involvement, and were higher in progressive than inactive disease. Whole-blood iron transferrin levels were more variable, and were significantly raised only in patients with marrow failure. PMID- 6248094 TI - Hepatitis-B surface antigen in tumour tissue and non-tumorous liver in black patients with hepatocellular carcinoma. AB - Formalin-fixed, paraffin-embedded sections of liver and tumour tissue obtained at necropsy from 44 southern African Blacks with hepatocellular carcinoma were stained for hepatitis-B virus surface antigen by immunofluorescence, immunoperoxidase and orcein techniques. The antigen was present in the serum of 68% of the patients. Staining for tissue antigen was positive in 45% of the patients. Non-tumorous hepatocytes alone stained positively in 22.5% of patients, tumour cells alone in 12.5% and both in 10%. Antigen was present in relatively few tumour cells and the amounts detected were small; it was more readily detectable in moderately differentiated than in poorly differentiated malignant cells. Identical results were obtained with immunofluorescence and immunoperoxidase staining, but the orcein stain failed to demonstrate the antigen in tumour cells. Cirrhosis was present in the non-tumorous liver in 70% of the patients. Antigen was detected in cirrhotic tissue in 43% of the patients with cirrhosis, and in non-tumorous liver tissue in 8% of those without cirrhosis, but this difference was not significant. The antigen frequency in tumour tissue was the same in patients with and without cirrhosis. No correlation was found between the presence of liver-cell dysplasia and the presence or absence of either the antigen or cirrhosis in the non-tumorous liver tissue. Ground-glass hepatocytes were seen in non-tumorous liver tissue of 5 patients, but not in tumour tissue. While 54% of the patients with antigenaemia had demonstrable tissue antigen, 10% of patients with tissue antigen had no detectable antigenaemia. PMID- 6248096 TI - Avian leukaemia viruses and haematopoietic cell differentiation. PMID- 6248095 TI - Factors affecting responses to murine oncogenic viral infections. AB - Silica specifically kills macrophages in vitro, and in vivo has been used as a method of determining the possible immunological or other roles of macrophages in a number of viral infections. In experiments reported here, injection of 30 or 50 mg silica i.p. increased the severity of the oncogenic effects of the murine sarcoma virus (MSV) and Friend virus (FV) in BALB/c mice. Unlike Herpes simplex and Coxsackie B-3 infections, however, passive transfer of adult macrophages to suckling mice did not protect the latter against MSV. In mice injected with silica, histological evidence of the compensatory proliferation of macrophages suggests that precursors of these cells may act as target cells for the virus and that this may override any immunosuppressive response effected by the silica. In addition, there was a considerable enhancing effect on the erythroproliferative response to both MSV and FV by injection of saline 5 h before the virus, and indeed to FV after only a simple abdominal needle puncture. We attributed this to the lymphopenic immunodepressive effects of stress, and our data may explain previously published findings of augmented oncogenic responses in mice after "normal" serum injections. Newborn BALB/c (FV-1b) mice were susceptible to N tropic FV, but developed resistance by 29 days of age. Antithymocyte serum (ATS) but not silica injections or adult thymectomy ablated this resistance. C57BL (FV 2r) mice were completely resistant to FV; however, those receiving FV and ATS developed late-onset leukaemia histologically characteristic of that produced by the helper component of the FV complex. PMID- 6248097 TI - Multiple telangiectatic glomus tumours [proceedings]. PMID- 6248098 TI - The effect of steroid and dithranol therapy on cyclic nucleotides in psoriatic epidermis. AB - Absolute values of both cAMP and cGMP leves were measured in the involved and uninvolved skin of psoriatic patients, and also the effect of topical therapy on these levels in the involved skin was studied. The mean cGMP level in the untreated psoriatic plaque was increased by 300% compared to the non-involved skin (which did not differ from normal skin), but no significant difference in cAMP levels was found. Epidermal stripping of uninvolved skin, which stimulates cell proliferation, did not change the cGMP level. Treatment of the psoriasis with dithranol caused the cGMP levels to return to normal, but a potent topical glucocorticoid, in contrast, produced no such decrease. This may imply that the two drugs act at different levels in suppressing cell replication, and dithranol may be a useful tool for the further investigation of cyclic nucleotide metabolism. PMID- 6248099 TI - Tumours of the anterior uvea. II. Intranuclear cytoplasmic inclusions in malignant melanoma of the iris. AB - Intranuclear cytoplasmic inclusions have been described previously in both human and animal tissue. So far as we are aware they are described in detail for the first time in this paper in 60 cases of malignant melanoma of the iris, usually in spindle cells. The light microscopic appearances are described, and electron microscopic studies of selected cases show clearly the genesis of these inclusions by cytoplasmic invagination of the nuclear membrane. Their significance is discussed. It is of interest that we have seen identical inclusions in malignant melanomas of the ciliary body, choroid, and conjunctiva but have not as yet reported our findings. PMID- 6248100 TI - Pig liver phosphomevalone kinase. 1. Purification and properties. AB - Pig liver phosphomevalonate kinase (EC 2.7.4.2) has been purified to homogeneity as shown by polyacrylamide gel electrophoresis. The molecular weight estimates range from 21,000 to 22,500. Each molecule is composed of one polypeptide chain. The presence of SH-containing reagents is essential for the preservation of enzymes activity at all steps in the purification. The enzyme shows absolute specificity for ATP and requires for activity a divalent metal cation, Mg2+ being most effective. The optimum pH for the enzyme ranges from 7.5 to over 9.5. Kinetics are hyperbolic for both substrates, showing a sequential mechanism; true Km values of 0.075 mM and 0.46 mM have been obtained for phosphomevalonate and ATP, respectively. Amino acid composition shows a high content of acid amino acids, one cysteine residue per molecule of enzyme, and the absence of methionine. The results obtained suggest that the enzyme plays no regulatory function in cholesterol biosynthesis in pig liver, although a variable enzyme content was detected in different livers. PMID- 6248101 TI - Pig liver phosphomevalonate kinase. 2. Participation of cysteinyl and lysyl groups in catalysis. PMID- 6248102 TI - Heparan sulfates from Swiss mouse 3T3 and SV3T3 cells: O-sulfate difference. AB - A difference in the extent of sulfation between the heparan sulfate isolated from Swiss 3T3 mouse cells and that from Swiss 3T3 cells transformed by the DNA virus SV40 has been reported previously. This variance is manifested by different chromatographic and electrophoretic properties. Heparan sulfates from the two cell types were treated with nitrous acid under conditions that gave selective deaminative cleavage of glucosaminyl residues with sulfated amino groups in order to define the nature of the difference in sulfation further. The O-sulfate containing fragments from the heparan sulfates were compared by gel filtration and ion-exchange chromatography. The results showed that the 3T3 heparan sulfate contains 8% more O-sulfate than does the SV3T3 heparan sulfate. Analysis of uronic acids revealed that both types of heparan sulfates contain 45% L-iduronic acid and 55% D-glucuronic acid. These and other observations indicate that the primary difference in sulfation between the 3T3 and SV3T3 heparan sulfates lies in the extent of O-sulfation. PMID- 6248103 TI - Pulsed electron paramagnetic resonance studies of the copper(II) site in galactose oxidase. PMID- 6248104 TI - Phosphorylation of nuclear poly(adenylic acid) polymerase by protein kinase: mechanism of enhanced poly(adenylic acid) synthesis. PMID- 6248105 TI - Investigations of substrate specificity and reaction mechanism of several kinases using chromium(III) adenosine 5'-triphosphate and chromium(III) adenosine 5' diphosphate. PMID- 6248106 TI - Characterization by electrophoresis of epidermal growth factor stimulated phosphorylation using A-431 membranes. PMID- 6248107 TI - Characterization of iron-sulfur clusters in rat liver submitochondrial particles by electron paramagnetic resonance spectroscopy. Alterations produced by chronic ethanol consumption. AB - Iron-sulfur clusters present in rat liver submitochondrial particles were characterized by ESR at temperatures between 30 and 5.5 K combined with potentiometric titrations. The spectral and thermodynamic characteristics of the iron-sulfur clusters were generally similar to those previously reported for pigeon or bovine heart submitochondrial particles. Clusters N-1a, N-1b, N-2, N-3 and N-4 of NADH dehydrogenase had midpoint oxidation-reduction potentials at pH 7.5 of -425, -265, -85, -240 and -260 mV, respectively. Clusters S-1 and S-3 of succinate dehydrogenase had midpoint potentials of 0 and +65 mV, respectively. The iron-sulfur cluster of electron-transferring flavo-protein-ubiquinone oxidoreductase exhibited the gz signal at g = 2.08 and had a midpoint potential of +30 mV. This signal was relatively prominent in rat liver compared to pigeon or bovine heart. Submitochondrial particles from rats chronically treated with ethanol (36% of total calories, 40 days) showed decreases of 20-30+% in amplitudes of signals due to clusters N-2, N-3 and N-4 compared to those from pair-fed control rats. Signals from clusters N-1b, S-1, S-3 and electron transferring flavoprotein-ubiquinone oxidoreductase were unaffected. Microwave power-saturation behavior was similar for both submitochondrial particle preparations, suggesting that the lower signal amplitudes reflected a lower content of these particular clusters. NADH dehydrogenase activity was significantly decreased (46%), whilst succinate dehydrogenase activity was elevated (25%), following chronic ethanol consumption. The results indicate that chronic ethanol treatment leads to an alteration of the structure and function of the NADH dehydrogenase segment of the electron transfer chain. This alteration is one of the factors contributing to the lower respiration rates observed following chronic ethanol administration. PMID- 6248108 TI - Cytochrome a-type terminal oxidase derived from Thiobacillus novellus. Molecular and enzymatic properties. AB - Cytochrome a-type terminal oxidase was purified from Thiobacillus novellus to an electrophoretically homogeneous state and some of its properties were studied. The enzyme shows absorption peaks at 428 and 602 nm in the oxidized form, and at 442 and 602 nm in the reduced form. The CO compound of the reduced enzyme shows peaks at 431 and 599 nm. The enzyme has 1 mol of haem a and 1 g-atom of copper per 55600 g and is composed of two kinds of subunit, of 32000 and 23000 daltons, respectively. The enzyme reacts rapidly with tuna, bonito and yeast cytochromes c as well as with T. novellus cytochrome c, while it reacts slowly with horse and cow cytochromes c. The reduction product of oxygen catalysed by the enzyme is water. PMID- 6248109 TI - Phosphorylation and dephosphorylation reactions by erythrocyte plasma membrane enzymes. AB - Human erythrocyte membranes contain a phosphoprotein phosphatase able to dephosphorylate membrane protein previously phosphorylated by the endogenous protein kinase. The level of dephosphorylation obtained after prolonged incubation is about one half of the phosphorylated residues. The characteristics of this enzyme are similar to those described for the cytoplasmic phosphoprotein phosphatase. In a membrane preparation the phosphorylation and dephosphorylation reactions can be repeated, at least twice, achieving similar levels of phosphate esterified or hydrolyzed. The coordination of these two enzyme systems might play a role in some of the functions attributed to the protein kinase system. PMID- 6248110 TI - Calcium-induced changes in polyphosphoinositides and phosphatidate in normal erythrocytes, sickle cells and hereditary pyropoikilocytes. PMID- 6248111 TI - Sensitivity of the (Na+ + k+)-atpase to state-dependent inhibitors. Effects of digitonin and Triton X-100. AB - Treatment of a purified (NA+ + 5+)-ATPase preparation from dog kidney with digitonin reduced enzymatic activity, with the (Na+ + k+)-atpase reaction inhibited more than the K+-phosphatase reaction that is also catalyzed by this enzyme. Under the usual assay conditions oligomycin inhibits the (Na+ + k+) atpase reaction but not the K+-phosphatase reaction; however, treatment with digitonin made the K+-phosphatase reaction almost as sensitive to oligomycin as the (Na+ + k+)-atpase reaction. The non-ionic detergents, Triton X-100, Lubrol WX and Tween 20, also conferred sensitivity to oligomycin on the K+-phosphatase reaction (in the absence of oligomycin all these detergents, unlike digitonin, inhibited the K+-phosphatase reaction more than the (Na+ + k+)-atpase reaction). Both digitonin and Triton markedly increased the K0.5 for K+ as activator of the K+-phosphatase reaction, with little effect on the K0.5 for K+ as activator of the (Na+ + k+)-ATpase reaction. In contrast, increasing the K0.5 for K+ in the K+ phosphatase reaction by treatment of the enxyme with acetic anhydride did not confer sensitivity to oligomycin. Both digitonin and Triton also increased the inhibition of the K+-phosphatase reaction by ATP and increased the inhibition by inorganic phosphate and vanadate. These observations are interpreted as digitonin and Triton favoring the E1 conformational state of the enzyme (manifested by sensitivity to oligomycin and a greater affinity for ATP at the low-affinity substrate sites), as opposed to the E2 state (manifested by insensitivity to oligomycin, greater sensitivity to phosphate and vanadate, and a lower K0.5 for K+ in the K+-phosphatase reaction). In addition, digitonin blocked activation of the phosphatase reaction by Na+ plus CTP. This effect is consistent with digitonin dissociating the catalytic subunits of the enzyme, the interaction of which may be essential for activation by Na+ plus nucleotide. PMID- 6248112 TI - Hexose and amino acid transport by chicken embryo fibroblasts infected with temperature-sensitive mutant of Rous sarcoma virus. Comparison of transport properties of whole cells and membrane vesicles. AB - The effect of transformation on hexose and amino acid transport has been studied using whole cells and membrane vesicles of chicken embryo fibroblasts infected with the temperature-sensitive mutant of the Rous sarcoma virus, TS-68. In whole cells, TS-68-infected chicken embryo fibroblasts cultured at the permissive temperature (37 degrees C) had a 2-fold higher rate of 2-deoxy-D-glucose uptake than the same cells cultured at the non-permissive temperature (41 degrees C). However, both the non-transformed and transformed cells had comparable rates of alpha-aminoisobutyric acid transport. Membrane vesicles, isolated from TS-68 infected chicken embryo fibroblasts cultured at 41 degrees C or 37 degrees C, displayed carrier-mediated, intravesicular uptake of D-glucose and alpha aminoisobutyric acid. Membrane vesicles from TS-68-infected chicken embryo fibroblasts cultured at 37 degrees C had an approx. 50% greater initial rate of stereospecific hexose uptake than the membrane vesicles from fibroblasts cultured at 41 degrees C. The two types of membrane vesicle had similar uptake rates of alpha-aminoisobutyric acid. The results of hexose and amino acid uptake by the membrane vesicles correlated well with those observed with the whole cells. Km values for stereospecific D-glucose uptake by the membrane vesicles from TS-68 infected chicken embryo fibroblasts cultured at 41 and 37 degrees C were similar, but the V value was greater for the membrane vesicles from TS-68-infected cells cultured at 37 degrees C. Cytochalasin B competitively inhibited stereospecific hexose uptake in both types of membrane vesicle. These findings suggest that the membrane vesicles retained many of the features of hexose and amino acid transport observed in whole cells, and that the increased rate of hexose transport seen in the virally-transformed chicken embryo fibroblasts was due to an increase in the number or availability of hexose carriers. PMID- 6248113 TI - Energy coupling in secondary active transport. PMID- 6248114 TI - The modified nucleotide constituents of human prostatic cancer cell (MA-160) poly(A)-containing RNA. AB - Cytoplasmic poly A(+) RNA from human prostatic cancer cells grown in the presence of 32P was isolated by affinity chromatography on columns of oligo(dT)-cellulose. The RNA was digested with RNAase T2 and the products of digestion were fractionated by two-dimensional electrophoresis. The resulting autoradiograms revealed the presence of many different cap groups as well as two internal modified nucleotide components. 19 different type 1 and type 2 'cap' groups were identified. The internal modified nucleotides were N6-methyl adenosine and a 2'-O methyl nucleotide possessing an unusual modified base. PMID- 6248115 TI - Differential association of transfer RNAs with the genomes of murine, feline and primate retroviruses. AB - The tRNAs that are bound to the genomic RNAs of several murine, feline, and primate retroviruses have been identified. Transfer RNAs were divided into those loosely bound and those tightly bound by stepwise thermal dissociation of the 70 S RNA. They were then identified and semiquantitated by aminoacylation. Proline tRNA is the most tenaciously bound tRNA in several strains of murine leukemia virus, two strains of feline leukemia virus, and the primate viruses simian sarcoma, baboon endogenous, and gibbon ape lymphoma. In the feline xenotropic virus, RD-114, tRNAGly is enriched in the most tightly bound fraction. In Mason Pfizer monkey virus, as in the murine mammary tumor virus, tRNALys is the tRNA most tenaciously bound to its genomic RNA. Besides the most tightly associated tRNA, one or more different tRNAs are found in relatively large amounts in association with the 70 S RNA. (For convenience, we refer to the largest RNA ccomplex (50-70 S) isolated from any of the retroviruses studies as '70 S' RNA.) These tRNAs can be distinguished from the most tightly bound tRNA by the fact that they can be dissociated at lower temperatures. However, they occur in the same relative abundance as the tightly bound tRNA. PMID- 6248116 TI - Physical properties of the complementary T4 RNA. AB - The complementary transcribed T4 RNA after self-annealing and RNAase treatment was isolated by gel chromatography and then used for further studies. From salt dependent RNAase resistance and melting studies it is evident that this RNA represents a genuine double-stranded structure. The base content of the isolated double-stranded RNA was found to be the same as total T4 mRNA. Sucrose gradient analysis and hydroxyapatite chromatography of T4 RNA, annealed early and late RNA, and of the isolated double-stranded RNA, gave results indicating that the complementary RNA is part of a RNA molecule and further that the size of the complementary regions are independent of the RNA molecules. Partial digestion of pulse-labelled late RNA with phosphodiesterase I prior to annealing with unlabelled early RNA, showed that the complementary regions on the mRNA are not located to the 5'- or 3'-end but randomly distributed along the T4 RNA molecules. PMID- 6248117 TI - Comparison of the action of streptomycin and neomycin on the structure of the bacterial ribosome. AB - The influence of streptomycin and neomycin upon the conformation of the ribosome has been investigated using spin-labeled and fluorescent analogs of the sulfhydryl reagent, N-ethylmaleimide. Changes in the electron paramagnetic resonance spectra or in the polarization of fluorescence of labeled ribosomes reveal that streptomycin alters the mobility of labels bound to the sulfhydryl group of protein S18 while neomycin affects the mobility of labels bound to the sulfhydryl groups of proteins S1, S21 and/or L10. It is also observed that both streptomycin and neomycin interfere with changes in the mobility of labels induced by storage under inactivating conditions. From these results, it is concluded that: 1. streptomycin and neomycin distort the conformation of the ribosome at different sites, streptomycin disturbing preferentially the area around the sulfhydryl group of protein S18 while neomycin affects the environment of the sulfhydryl groups of proteins S1, S21 and/or L10; 2. streptomycin and neomycin interefere with the ability of the ribosome to undergo conformational changes. PMID- 6248118 TI - Effect of polyamines on ADP-ribosylation by chick-embryo-liver nuclei. AB - Effects of polyamines on poly(ADP-ribose) formation and DNA synthesis in the chick-embryo-liver nuclei were investigated. When 14-day chick-embryo-liver nuclei were incubated with [3H]NAD in the presence of 1 mM spermine, 2.5 mM spermidine, or 3.5 mM putrescine, a 9-fold increase in poly)ADP-ribose) formation was observed. Nuclei treated with nuclease showed high poly(ADP-ribose) synthetase activity as spermine-treated nuclei. However, no further increase in the polymer formation by polyamines was detected in the nuclease-treated nuclei. We found that an increase in the polymer formation by spermine was the result of an increase in both chain length and chain number of the polymer at 2.3- and 6 fold, respectively. The major ADP-ribosylated proteins were determined as two non histone proteins of Mr 130 000 and 70 000. The experiment of DNA synthesis with nuclei ADP-ribosylated in the presence of spermine showed a 7-fold increase in [3H]dTMP incorporation into the acid-inaoluble fraction. A similar stimulation was also found with nuclei treated with other polysmines, spermidine and putrescine, in the presence of NAD. These results indicate that DNA synthesis in growing tissues containing polyamines at high levels, such as is the case with tumors and the fetus, is stimulated by polyamine-mediated ADP-ribosylation of the nuclear proteins. PMID- 6248119 TI - Effects of local anesthetics on guanyl nucleotide modulation of the catecholamine sensitive adenylate cyclase system and on beta-adrenergic receptors. AB - Tetracaine and other local anesthetics exert multiple actions on the catecholamine-sensitive adenylate cyclase system of frog erythrocyte membranes. Tetracaine (0.2--20 mM) reduces the responsiveness of adenylate cyclase to (a) guanyl-5'-yl-imidodiphosphate and (b) isoproterenol in the presence of GTP or guanyl-5'-yl-imidodiphosphate. Local anesthetics did not affect (a) basal enzyme activity, and (b) enzyme responsiveness to NaF. Tetracaine inhibited stimulation of adenylate cyclase by guanyl-5'-yl-imidodiphosphate over the whole range of nucleotide concentrations. By contrast, inhibition by tetracaine of isoproterenol activity in the presence of GTP was significant only if GTP concentrations exceeded 10(-7) M. Tetracaine also competitively inhibited binding of both the antagonist [3H]dihydroalprenolol and the agonist [3H]hydroxybenzylisoproterenol to beta-adrenergic receptors. However, it was twice as potent in inhibiting [3H]hydroxybenzylisoproterenol as [3H]dihydroalprenolol binding. The greater potency for inhibition of agonist binding was due to the ability of the anesthetics to promote dissociation of the high-affinity nucleotide sensitive state of the beta-adrenergic receptor induced by agonists. Other local anesthetics mimicked the effects of tetracaine on adenylatecyclase and in dissociating high-affinity agonist-receptor complexes. The other of potency for both processes was dibucaine greater than tetracaine greater than bupivacaine greater than lidocaine which agrees with their relative potencies as local anesthetics. By contrast, a different order of potency was observed for competitive inhibition of [3H]dihydroalprenolol binding: dibucaine greater than tetracaine greater than greater than lidocaine greater than bupivacaine. PMID- 6248120 TI - Prostaglandin E1 binding and adenylate cyclase activation in normal and transformed fibroblasts. AB - The binding of [3H]prostaglandin E1 to membranes of clones of normal rat kidney fibroblasts (NRK cells) has been measured. Cell lines that responded to prostaglandin E1, such as NRK and NRK transformed with Schmitt-Ruppin strain of Rous sarcoma virus (SR-NRK cells), have a high affinity prostaglandin E1 binding site. Murine-sarcoma-virus-transformed lines of NRK cells are unresponsive to prostaglandin E1 and have reduced prostaglandin E1 binding Exposure of cells to prostaglandin E1 results both in decreased prostaglandin E1 responsiveness and reduced prostaglandin E1 binding. Activation of adenylate cyclase is correlated to binding of prostaglandin E1 to receptors in both NRK and SR-NRK cell membranes. Mathematical models suggest that GTP decreases the affinity of hormone for its receptor while increasing the catalytic efficiency of adenylate cyclase, and that aggregates of occupied receptors may play an important role in the activation of adenylate cyclase. PMID- 6248121 TI - Specific S-methylglutathione incorporation into a nematocyst-rich fraction of hydra. AB - 1. Specific S-[C]methylglutathione incorporation from Hydra japonica into a nematocyst-rich subcellular fraction was observed. 2. This specific incorporation is not rapid reversible binding, as shown by the lack of saturation of the reaction with time. 3. Saturating kinetics of specific incorporation rate with S [14C]methylglutathione concentration suggests the existence of intermediate reversible complex between a macromolecular and S-[14C]methylglutathione. 4. Activity of specific incorporation could be solubilized by Triton X-100 treatment of the nematocyst fraction, showing that the incorporation is not due to transport processes. 5. The incorporation was markedly diminished by the addition of cold trichloroacetic acid or urea, or by heat-treatment after the incorporation, showing that the complex is not stabilized by chemical bonding. 6. No chemical changes of free S-[14C]methylglutathione were detected in the reaction mixture, showing that the macromolecule interacting with S [14C]methylglutathione is not a catalyzing enzyme. 7. These results suggest that this is a new type of glutathione incorporation and could be explained by a type of receptor protein which accumulates glutathione molecules. PMID- 6248122 TI - Degradation of the subunits of receptor-bound human choriogonadotropin by Leydig tumor cells. AB - Biologically active, iodine-labeled derivatives of human choriogonadotropin in which all the iodine is localized either in the alpha or beta subunits have been prepared. It is found that upon binding to Leydig tumor cells these derivatives are ultimately degraded to 3'-monoiodotyrosine. A comparison of the rates of degradation of the derivatives labeled exclusively in the alpha or beta subunits show that the alpha subunit is degraded somewhat faster than the beta subunit. It was also found that NH4Cl, chloroquine and leupeptin inhibited the degradation of both subunits to the same extent. These results show that the Leydig tumor cells degrade both subunits of the receptor-bound human choriogonadotropin, and suggest that the two subunits are degraded by the same mechanism(s). PMID- 6248123 TI - Spin-trapping and direct electron spin resonance investigations of the redox metabolism of quinone anticancer drugs. AB - The superoxide free radical has been spin trapped in microsomal incubations containing adriamycin, daunorubicin, and mitomycin C. The time sequence of the appearance of the spin-trapped superoxide and the semiquinone radical metabolite of these quinone-containing anticancer drugs indicates that air oxidation of the semiquinone is responsible for the superoxide formation. Superoxide dismutase prevents the formation of the superoxide spin adducts. Microsomal incubations containing anthracyclines intercalated in DNA produce much less superoxide than incubations free of DNA. The first unambiguous ESR evidence for the semiquinone metabolite of mitomycin C in a biological system is also presented. PMID- 6248124 TI - Nuclear magnetic resonance study of squid giant axon. AB - Using a spin-echo technique, the spin-lattice and spin-spin relaxation times (T1 and T2) of water protons in a single nerve fiber (giant axon of squid) were determined. Similar measurements were also carried out on axoplasm extruded from these nerve fibers. It was found that the relaxation times of water protons of both the intact fiber and the extruded axoplasm are approximately equal (and much less than those of a free solution), suggesting that the relaxation times of cellular water are shortened mainly by water-protein interactions rather than by water-membrane interactions. PMID- 6248125 TI - Inhibition of a plasminogen activator from oncogenic virus-transformed mouse cells by rabbit antibodies against the enzyme. AB - Antisera were raised in rabbits against an electrophoretically pure 48 000 dalton plasminogen activator from mouse cells transformed by an oncogenic virus. The IgG fraction of the antisera inhibited 48 000 dalton mouse plasminogen activators from a variety of sources (neoplastic and nonneoplastic), a 29 00) dalton plasminogen activator from mouse urine and a 48 000 dalton plasminogen activator from rat urine. No inhibition was observed of a 75 000 dalton plasminogen activator extracted from mouse lung, of mouse plasmin or of plasminogen activators from human urine and from oncogenic-virus transformed chicken cells. The IgG antibodies were stronger and more specific inhibitors of the 48 000 dalton mouse plasminogen activator than any previously tested compounds. PMID- 6248126 TI - Inhibition of lipolysis in hamster adipocytes with selective alpha-adrenergic stimuli. Functional characterization of the alpha-receptor. AB - This communication shows the relative potencies of the alpha-agonists clonidine, methoxamine, methyl norepinephrine and phenylephrine in producing inhibition of lipolysis. At cell densities greater than 15 mg cell/ml lipolysis activated by either 1-methyl-3-isobutyl xanthine or adenosine deaminase was inhibited by alpha adrenergic stimuli with a rank order of potency of clonidine greater than methoxamine greater than methyl norepinephrine; phenylephrine produced a further stimulation of lipolysis. At the same cell density isoproterenol-accelerated lipolysis was inhibited by alpha-adrenergic stimuli with a rank order of potency of phenylephrine greater than methoxamine greater than clonidine greater than methyl norepinephrine. When the density of fat cells was reduced to less than 5 mg/ml, clonidine was a more effective inhibitor of isoproterenol-activated lipolysis thatn phenylephrine. Lipolysis that was activated by dibutyryl cyclic AMP, ACTH or cholera enterotoxin was not reduced by any alpha-adrenergic agent. Under conditions when clonidine failed to inhibit catecholamine-activated lipolysis (i.e., at cell densities greater than 15 mg/ml), it failed to antagonize the antilipolytic activity of phenylephrine. The antilipolytic activities of clonidine and phenylephrine were most effectively antagonized by the blocking drugs phentolamine and yohimbine; in contrast, phenoxybenzamine and prazosin were less effective blockers. These data indicate that the alpha adrenergic receptor on hamster fat cells is similar to presynaptic alpha adrenergic receptors. The data further suggest the possibility that phenylephrine may exert its action through a separate alpha-adrenergic receptor mechanism. PMID- 6248127 TI - The stimulation of sperm metabolism by a factor associated with eggs and by 8 bromo-guanosine 3',5'-monophosphate. PMID- 6248128 TI - Characterization of the hormone-sensitive Ca2+ uptake activity of the hepatic endoplasmic reticulum. AB - The characteristics and kinetics of calcium uptake activity were studied in isolated hepatic microsomes. The sustained accumulation of calcium was ATP- and oxalate-dependent. Glucagon increased microsomal Ca2+ uptake upon either in vivo injection, or in vitro perfusion of the hormone in the liver. In contrast, the effect of insulin depended on the route of administration. Calcium accumulation by subsequently isolated hepatic microsomes increased when insulin was injected intraperitoneally whereas it decreased when the hormone was perfused directly into the liver. These effects of glucagon and insulin were dose dependent. When insulin was added to the perfusate prior to the addition of glucagon, insulin blocked the glucagon-stimulated increase in microsomal Ca2+ uptake. Cyclic AMP mimicked the effect of glucagon on microsomal Ca2+ accumulation when the cyclic nucleotide was perfused into the liver. The effects of glucagon and insulin on the kinetics of hepatic microsomal Ca2+ uptake were investigated. In microsomes isolated from perfused rat livers treated with glucagon the V of the uptake was significantly increased over the control values (12.2 vs. 8.6 nmol Ca2+ per min per mg protein, P less than 0.02). In contrast, the addition of insulin to the perfusate significantly decreased the V of Ca2+ uptake by subsequently isolated microsomes (6.8 vs. 8.3 nmol Ca2+ per min per mg protein, P less than 0.05). However, neither hormone had an effect on the apparent Km for Ca2+ (4.1 +/- 0.5 microM) of the reaction. The effect of these hormones on the activity of Ca2+ stimulated ATPase was also studied. No significant changes in either V or Km for Ca2+ of the enzymatic reaction were detected. PMID- 6248129 TI - ATP enhances cyclic AMP accumulation by intact P388 mouse lymphoma cells. AB - One of the characteristics of malignant cells is a poor response to hormones and a low level of cyclic AMP. Whilst this is true of intact P388 mouse lymphoma cells, high levels of adenylate cyclase (ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1) activity can be measured in particulate preparations of these cells. When ATP is added to the incubation medium of intact lymphoma cells, the cyclic AMP level is enhanced. This effect of ATP is not mediated by adenosine, nor is it enhanced by NaF. The ATP content of the lymphoma cells is much lower than that of CH23 Chinese hamster fibroblast and PCM3 hybrid cells, whose cyclic AMP levels are not affected by the presence of ATP. This suggests that adenylate cyclase, in the lymphoma cells, is bathed in a pool which is deficient in substrate. The substrate concentration of this pool is thought to be elevated by addition of ATP to the incubation medium with ATP, itself, crossing the plasma membrane. PMID- 6248130 TI - Trypsin modifies the activity of adenylate cyclase from normal, malignant and hybrid mammalian cells. AB - Adenylate cyclase (ATP pyrophosphate-lyase (cylizing), EC 4.6.1.1) activity, measured in homogenates of normal, malignant and hybrid mammalian cell lines, is enhanced and subsequently inhibited by increasing concentrations of trypsin (EC 3.4.21.4). Treatment of intact cells with trypsin appears to cause latent activation of adenylate cyclase (i.e. activation which is only expressed after homogenization of the cells). Conversely, adenylate cyclase activity of a normal Chinese hamster fibroblast cell line is inhibited in intact cells by trypsin through the degradation of some site on the outer surface of the plasma membrane. The prostaglandin E1 receptor is not affected by trypsinization of cells. PMID- 6248131 TI - Assay of nuclear estradiol receptor by exchange on glass fiber filters. AB - A glass fiber filter exchange assay for nuclear estradiol receptor in human endometrium has been developed. It permits both exchange and measurement of bound radioactivity to be performed without any transfer of the nuclear preparations. Suspensions of nuclei containing estradiol-receptor complexes are adsorbed onto glass fiber filters. Receptor sites, both empty and occupied by endogenous hormone, are labelled by incubation with 20 nM [3H]estradiol without (total binding) or with 2 microM radioinert estradiol (nonspecific binding). Buffer containing unbound radioactive estradiol is then drained, the filters washed, transferred into vials and counted in toluene-based scintillator. Following removal from the scintillator, DNA content of the filters can be measured by the Burton procedure. This exchange technique is easy and specific, with accuracy and precision similar to those of the technique of Bayard et al. (Bayard, F., Damilano, S., Robel, P. and Baulieu, E.E. (1978) J.Clin. Endocrinol. Metab. 46, 635-648). It offers the advantage of increased sensitivity, allowing receptor determinations on nuclear samples containing more than 10 microgram DNA. Approximately 20 measurements can be made from 50 mg tissue (wet weight). PMID- 6248132 TI - [Structural-functional organization of protein hormone molecules]. AB - Our experimental results and literature data based on present-day concepts of molecular evolution of proteins have formed the basis for a hypothesis on the structural-functional organization of protein hormone molecules. This hypothesis postulates the existence of three types of the peptide chain sites, which play different roles in the biological action of hormones, i.e. effector (active), acceptor (binding) and accessory ones. The local similarity spectra have been computed and used for a comparison of the amino acid sequences of related hormones belonging to different groups. The positions of maxima, slopes and minima in these spectra of the molecules of peptide and some protein hormones are correlated with a most probable localization of the effector, acceptor and accessory sites, respectively. PMID- 6248133 TI - [Effect of 2,3-dimercaptopropanol on electron transfer in the energy coupling site 2 of the respiratory chain: evidence for the Q-cycle hypothesis]. AB - Incubation of submitochondrial particles from bovine heart with 2,3 dimercaptopropanol (British antilewisite, BAL) results in inhibition of the respiratory chain between cytochromes b and c. BAL exerts no pronounced effect on the spectral and redox properties of cytochromes b566 and b562. In the BAL treated submitochondrial particles antimycin brings about the bathochromic shift of the cytochrome b562 absorption alpha-band, but does not induce "extra reduction" of cytochromes b. Upon a combined effect of antimycin and BAL the reduction of cytochromes b by succinate is inhibited. Whereas neither antimycin nor BAL alone prevents this reaction. The data obtained suggest the existence of two pathways of electron transfer from succinate to cytochromes b, one of which is blocked by antimycin and the other one by BAL. These two pathways form a cyclic loop of electron transport, in accordance with the Mitchell's "protonmotive CoQ-cycle" hypothesis. The traditional scheme of linear arrangement of the respiratory carriers in the succinate--cytochrom c reductase span of the electron transfer chain, as well as the Wikstrom--Berden's branched model, do not provide satisfactory explanation of the mode of BAL inhibitory action. PMID- 6248134 TI - Postnatal development of jejunal sucrase: independence from cyclic AMP. AB - It has previously been shown that jejunal sucrase activity becomes increasingly responsive to glucocorticoids between the postnatal ages of 4 and 15 days. This study examines the possibility that cyclic AMP is the mediator of the increasing responsiveness. When dibutyryl cyclic AMP was administered concomitantly with glucocorticoid to rat pups aged 6 days, there was no enhancement of sucrase activity in pups sacrificed either 30 or 54 h later. To check for short-lived effects of cyclic AMP, pups aged 5 days were pretreated with glucocorticoid for 2 days to elicit sucrase activity, then received dibutyryl cyclic AMP by injection and were sacrificed 1, 3 and 6 h later. Once again there was no effect of cyclic AMP on sucrase activity. The final approach was to use cholera enterotoxin to stimulate epithelial adenylyl cyclase in jejunal segments in vivo. Under these conditions the stimulation of fluid secretion served as positive evidence that intracellular concentrations of cyclic AMP were elevated. However, once again there was no stimulation of sucrase activity. It is concluded that cyclic AMP does not mediate the increasing responsiveness of the developing intestine to glucocorticoids. PMID- 6248135 TI - Role of thyroid hormones in the normal and glucocorticosteroid hormone-induced evolution of carbamoylphosphate synthase (ammonia) and arginase activity in perinatal rat liver. AB - Administration of thyroid hormones causes a dose-dependent increase in carbamoylphosphate synthase (ammonia) and arginase activities in fetal rat liver but not in neonatal rat liver. Simultaneous administration of thyroid and glucocorticosteroid hormones enhances enzyme accumulation still further in the fetus. When administered before birth, the relative potencies of T4 and reverse T3, compared to T3 are 20--25% and 1--20%, respectively. Both before and after birth, thyroid hormones enhance DNA content of the liver. Hypophysectomy of rat fetus reduces the carbamoylphosphate synthase activity level in hepatocytes to 30 -40% of that in intact animals. Thyroid and glucocorticosteroid hormone administered individually to hypophysectomized animals stimulate enzyme activity 2- to 3-fold; and if administered simultaneously, 4- to 6-fold. Premature delivery with continuation of thyroid and/or glucocorticosteroid hormone treatment started before birth shows uninterrupted enzyme accumulation profiles. Delaying birth by progesterone treatment of the dam leads to uninterrupted but reduced rates of enzyme accumulation in hepatocytes. PMID- 6248136 TI - Relationship of 2,3-diphosphoglycerate and 2,3-diphosphoglycerate mutase in various mammals. AB - To investigate a possible mechanism involved in the regulation of 2,3 diphosphoglycerate (2,3-DPG) synthesis, 2,3-DPG mutase (DPGM) was measured in different mammals presenting large differences in 2,3-DPG concentration between fetal, neonatal and adult life to see the activity of this enzyme, necessary for 2,3-DPG synthesis, was related to the levels of 2,3-DPG. The data demonstrated that the minimal levels of 2,3-DPG in the adult sheep are likely due to the very low levels of DPGM. Also these findings show that the increases in 2,3-DPG levels, found in the newborn sheep during the 1st week of life, in adult rabbit and guinea pig when compared with their fetuses, are not due to an increase in levels of the DPGM. PMID- 6248137 TI - Agonist-dependent desensitization of myometrial beta-adrenergic catecholamine sensitive adenylate cyclase. PMID- 6248138 TI - Regulation of sea urchin sperm cyclic AMP-dependent protein kinases by an egg associated factor. PMID- 6248139 TI - Modulation of cell proliferation in cultured postimplantation embryos by cyclic AMP. PMID- 6248140 TI - Direct inhibitory effect of enclomiphene citrate and estradiol on testis functions in hypophysectomized rats. PMID- 6248141 TI - Effects of maternal parathyroid glands and vitamin D3 metabolites on fetal growth and fetal liver glycogen stores in thyro-parathyroidectomized pregnant rats. PMID- 6248142 TI - [Mechanism of disorders in neurotrophic regulation of the level of striated skeletal muscle polarization by botulinum toxin]. AB - Muscle reinnervation was studied in experiments on rats given intramuscular injection of sublethal doses of botulinum toxin. It has been established that botulinum toxin not influencing the formation of functioning myoneural synapses leads to long-term persistence of depolarization of reinnervated muscle cells without changes in passive biophysical properties of their sarcoplasmatic membranes. PMID- 6248143 TI - [Probing the structure of bacterial deoxyribonucleoproteins with exogenous and endogenous nucleases]. AB - During digestion of deoxyribonucleoproteins (DNP) of gram-negative bacteria by micrococcal nuclease and Ca2+, Mg2+-dependent endonuclease in situ regular series fragments-and large nuclease-resistent fragments of DNP were revealed by electrophoresis. The DNP length of the smallest DNP-fragment was tentatively 120 140 base pairs. In investigated bacterial species DNP contained at least two basic proteins which had electrophoretic mobility similar to that of histone H4 of eucaryot. It is suggested that bacterial DNPs have common regular structure. PMID- 6248144 TI - [Participation of GABA-ergic structures in producing the effects of haloperidol]. AB - A study was made of the effect of haloperidol on convulsions induced in mice by bicuculline and thiosemicarbazide and on the recovery cycles of the primary response in the rat sensorimotor cortex. In doses of 0.3--0.5 mg/kg producing a tranquilizing effect, haloperidol exerts a protective action in convulsions induced by bicuculline blocking of the GABA receptors and enhances the depression of the testing response during recovery cycle of the rat sensorimotor cortex primary response. It means that over this dosage range haloperidol potentiates GABA-induced effects. An increase in the neuroleptic dose up to 1--2 mg/kg entails disappearance of the efficacy shown by both the tests. The authors' own and reported data suggest an important role played by the postsynaptic GABA positive effect in realization of the tranquilizing action of haloperidol and other neurotropic agents. PMID- 6248145 TI - [Distant intercellular electromagnetic interactions in a 2 tissue culture system]. PMID- 6248146 TI - [Qualitatively similar effects of microiontophoretic applications of corticotropin and hydrocortisone in the hippocampal and hypothalamic neurons of rabbits]. AB - A comparison was made of the responses of hypothalamic, septal and hippocampal neurons to microionotophoretic applications of corticotropin (ACTH) and hydrocortisone. A reliable positive correlation of medium significance was found in the hippocamp, less pronounced positive correlation in the hypothalamus and no correlation in the septum. The data obtained indicate that the hippocampal and hypothalamic brain structures are characterized by functional similarity of the mechanisms of neuronal sensitivity to each hormonal substance. It is unlikely that the neurophysiological processes participating in the response of nervous cells to ACTH and hydrocortisone applications are similar, this suggestion being supported by the presence of a number of exceptions and absence of the correlation in the septum. PMID- 6248147 TI - [Thyroxine: structural transformations in the membranes of rabbit skeletal muscle sarcoplasmic reticulum]. AB - The structure of the membranes of sarcoplasmic reticulum fragments (SRF) normally and in thyrotoxicosis was studied by the spin-label and spin-probe methods and by chemifluorescence. The curves of temperature dependence of the regularity parameter show a typical break for the spin probe at 20 degrees C shifted by 4 degrees C to sower temperatures for thyrotoxins. The same shift was observed with temperature dependence for the correlation period of the spin label covalently bound to the thiol groups of Ca2+ dependent ATPase of sarcoplasmic reticulum. The latent period of thyrotoxins was reduced and the chemifluorescence intensity increased. The results obtained suggest the occurrence of considerable changes in the structure of SRF membranes in thyrotoxicosis. PMID- 6248148 TI - [Changes in the serum acid phosphatase activity of guinea pigs poisoned with C1 perfringens type A toxin and a mixture of toxin and a broth culture filtrate]. AB - It was shown in experiments on guinea pigs that the injection of C1. perfringens type A toxoid induced an increase in acid phosphatase activity of animal blood serum. The action of the toxoid increased under the effect of C1. butyricum cultural filtrate, which gave rise to an earlier enhancement of the specific activity of the enzyme as compared to the injection of the toxoid alone. Increased activity of acid phosphatase may play a pathogenetic role in cases of anaerobic infection caused by association of C1. perfringens and C1. butyricum. PMID- 6248149 TI - [Expression of virus-specific RNA in cells of mice infected with Mazurenko and Rauscher viruses]. AB - Organs of mice with leukemia induced by Rauscher and Mazurenko viruses contain different amounts of virus-specific RNA. In Mazurenko virus-induced leukemia, virus-specific RNA content reached the maximum in the thymus and lymph nodes. Hybridization level of RLV 3H DNA transcript with RNA from mouse cells with RLV induced leukemia amounted to 90% while in cells of mice with Mazurenko virus induced leukemia it did not exceed 60%. PMID- 6248150 TI - [Cyclic nucleotides of human and animal glial tumors]. AB - Studies on the level of cyclic nucleotides (cAMP and cGMP) in human and animal glial tumours showed that the content of both nucleotides, especially that of cAMP, decreases in all the tumours. The cAMP/cGMP ratio also drops down. Concurrently it appears to be the most consistent parameter of nucleotide metabolism both in brain tissue and in human or animal glial tumours. The growing tumour affects cAMP and cGMP metabolism not only in the involved but also in the other hemisphere. No principal differences between human and animal tumours have been revealed in the content of cyclic nucleotides and its variation in tumour tissue. PMID- 6248151 TI - Chlorpromazine inhibition of granulocyte superoxide production. AB - Superoxide production by granulocytes is a result of the activation of an NAD(P)H dependent oxidase present in the plasma membrane. Chlorpromazine (5-50 muM) prolongs the time necessary to activation of the superoxide generating system and inhibits the extent of activation. When chlorpromazine is added after activation, there is an inhibition of further superoxide production. These effects are seen with digitonin, phorbol myristate acetate, and opsonized zymosan stimulated guinea pig and human granulocytes. Other phenothiazines (1-20 muM) and tetracaine (0.1-1.0 muM) produce similar effects. Lidocaine (1-10 mM) inhibits superoxide production but has no effect on the rate of activation. The effect of chlorpromazine on the rate of activation is reversible, but its effect on extent of activation is unaffected by extensive washing. Incubation of granulocytes with chlorpromazine results in decreased activation of the plasma membrane superoxide generating NADPH oxidase. Chlorpromazine also competes with NADPH for the membrane oxidase. These data and previously published results provide the basis of a model for the activation of the superoxide generating system. PMID- 6248152 TI - In vitro interactions of PGE and cAMP with murine and human erythroid precursors. AB - Addition of prostaglandins of the E series (PGE1, PGE2) in methylcellulose cultures of murine marrow results in a dose-dependent inhibition of the cloning efficiency of both BFU-E and CFU-C. However, CFU-E growth is unaffected. The inhibitory action of PGE is progressively overcome by increasing amounts of colony-stimulating factor (CSF), and with some limitations, also of erythropoietin (Ep). Addition of PGF2 alpha' associated or not with indomethacin, does not exert any significant effect on these hemopoietic precursors. In an attempt to unvail the mechanism(s) underlying these phenomena, dibutyryl-cyclic AMP (db-cAMP), theophylline (an inhibitor of phosphodiesterase), or theophylline + PGE were plated at various concentrations. Both db-cAMP and theophylline induce an inhibitory influence on both BFU-E and CFU-C growth, which mimicks that by PGEs; additionally, theophylline potentiates the inhibitory action of PGE1. In all these studies, the CFU-E number was not significantly modified. PGE action on BFU-E proliferation is clearly species-dependent, since PGE1 addition to human marrow methylcellulose cultures induces a significant enhancement of the number of both BFU-E and CFU-E derived colonies. This action was abolished upon removal of adherent cells, thus suggesting that PGE1 evokes a release of factor(s) enhancing human erythroid colony growth by adherent cells. PMID- 6248153 TI - Characteristics of arterial plasma membrane in renovascular hypertension in rats. AB - Protein content, enzymatic activites and Ca2+ accumulation capacities were studied in plasma membrane fractions isolated from mesenteric arteries of rats made hypertensive by renal artery stenosis with and without contralateral nephrectomy, i.e., one-kidney, one clip (1-KHR) and two-kidney, one clip (2-KHR) hypertension, respectively. Both types of renovascular hypertension showed similar vascular plasma membrane abnormalities which included increased total protein contents, enhanced alkaline phosphatase activities and reduced ATP dependent Ca2+ accumulation compared to control values. The altered alkaline phosphatase activity and ATP-dependent Ca2+ accumulation appeared to be associated with blood pressure elevation in both types of hypertension and may be related to the elevation of blood pressure insensitive to captopril (SQ 14,225) in 1-KHR and 2-KHR. These results are consistent with the current concept of biochemical abnormalities of arterial smooth muscle in the development ostem. PMID- 6248154 TI - Cyclic AMP levels in blood cells from a short-cycle manic-depressive subject. AB - Erythrocyte and leucocyte numbers and cyclic AMP content were monitored weekly in a mentally defective short-cycle manic-depressive woman. The erythrocyte count remained relatively constant but cyclic AMP content when manic was significantly higher than when depressed, and the mood and biochemical data appeared to have the same periodicity, with coincident peaks and troughs. Total leucocytes were related to mood, with peaks in the manic phase. Mononuclear cyclic AMP content varied without relation to manic or depressive phases. PMID- 6248155 TI - Tests for infectious mononucleosis. PMID- 6248156 TI - Multiple sclerosis: what can and cannot be done. PMID- 6248157 TI - Diet and bowel cancer. PMID- 6248158 TI - Vitamin D3 in osteoporosis. PMID- 6248160 TI - Investigating constipation. PMID- 6248159 TI - Diabetic glucose control, lipids, and trace elements on long-term guar. PMID- 6248161 TI - Diagnosis of infectious mononucleosis. PMID- 6248162 TI - Proctitis and herpes simplex virus in homosexual men. AB - In a study of the prevalence of rectal infection with herpes simplex virus (HSV) in a group of homosexual men the magnified appearance of the rectal mucosa correlated with isolation of the virus. HSV was isolated from rectal material from five of 77 men with proctitis of unknown cause but from none of 44 control patients without proctitis; two of four men with HSV proctitis were asymptomatic. Thus, the magnified rectal mucosal image, showing severe congestion, haemorrhage, and pus, appears to be a sensitive indicator of the presence of HSV proctitis. PMID- 6248163 TI - Influence of the visual cortex upon receptive field organization of lateral geniculate cells in rabbits. AB - In anesthetized rabbits, the receptive fields of lateral geniculate cells were mapped prior to and following the interruption of the corticogeniculate feed back. Visual cortex (V.C.) was depressed by a focal application of 3 M KCl. The responsiveness of the V.C. was verified by monitoring the visually evoked potentials. In off- and on-center cells, the surround excitatory responses were remarkably reduced and even fully abolished in most units. In contrast, the center excitation remained unmodified. These effects were reversible. In some on center units the center response had also decreased, and was replaced by an evoked inhibitory response. Relay cells and interneurons which yielded on and off responses over the entire area of the receptive field exhibited a loss of only one of the evoked discharges. It is concluded that the V.C. exerts mostly a specific desinhibitory action upon the geniculate network. This action affects either the center or the surround responses differentially. The results are compared with those obtained from cats. PMID- 6248164 TI - A comparative physiological and pharmacological study of cat and rabbit carotid body chemoreceptors. AB - Carotid bodies and their nerves were excised from rabbits or cats, cleaned of surrounding connective tissue and placed in a chamber through which mammalian saline equilibrated with different gas mixtures was allowed to flow. Single fibers were isolated and identified as chemosensory by their response to hypoxia, hypercapnia, or NaCN. Mass receptor potentials (recorded at some distance from the sensory nerve endings) were evoked by the same stimuli and registered as close as possible to the carotid body. Both cats and rabbits exhibited receptor depolarization and an increased discharge in response to NaCN, hypoxia, hypercapnia and cyanide. However, the effects of some pharmacological agents were quite different in rabbits and cats. In the rabbit, ACh 10-100 microgram and carbachol 1-10 microgram produced receptor hyperpolarization and discharge depression followed by discharge increase. Nicotine 0.3-20 microgram induced receptor depolarization and increased chemosensory discharge frequency. Nicotinic stimulation was antagonized by D-tubocurarine 10(-6)-10(-4) g/ml. Pilocarpine 2 50 microgram hyperpolarized the receptors and depressed discharge frequency. Pilocarpine-induced depression was reduced by atropine 10(-6) g/ml. Dopamine 5 100 microgram depolarized the receptors and increased the chemosensory discharge frequency. This effect of dopamine was reduced by haloperidol (10(-11)-10(-7) M). In the cat, ACh, carbachol and nicotine (same doses as those used in rabbits) induced receptor depolarization and increased the sensory discharge frequency. Pilocarpine (up to 50 microgram) had little effect on either discharge frequency or the receptor potential. Dopamine 5-100 microgram induced receptor hyperpolarization and depression of discharge frequency, and these effects were reduced by haloperidol. PMID- 6248165 TI - Electrophysiological evidence for a projection of the periaqueductal gray matter to nucleus raphe magnus in cat and rat. PMID- 6248166 TI - Evidence that a GABAergic mechanism at nucleus ambiguus influences reflex-induced vagal activity. PMID- 6248167 TI - Kainic acid differentiates GABA receptors from benzodiazepine receptors in the rat cerebellum. PMID- 6248168 TI - Adenylate cyclase-phosphodiesterase system in rat olfactory bulb and cerebral cortex during the postnatal period. Effects of growth restriction. PMID- 6248169 TI - Electrophoretic study of pipecolic acid, a biogenic imino acid, in the mammalian brain. AB - Pipecolic acid (PA), one of the imino acids, is a normal constituent in the mammalian brain. It is said that PA is a major intermediate of lysine metabolism in the rat brain. Biochemical studies have suggested that PA may be involved in the regulation of synaptic mechanism in the CNS. Moreover, the pathophysiological significance of PA has been also suggested by some investigators. However, there has so far been no good evidence based on the comprehensive electrophysiological experiments. Using unit recording and microelectrophoretic technique, the action of PA on single neuron activities in the rat brain was examined. PA depressed the firing of 88 out of 115 cortical neurons tested. Only 2 were excited and 25 remained unaffected. All the identified hippocampal pyramidal neurons examined were uniformly inhibited. It has been reported that PA inhibits the uptake of GABA into the brain slices and enhances the release of GABA from the slices. Thus, it is likely that the inhibitory response due to PA may have some connections with GABAergic transmission. On the other hand, it remains to be clarified whether the specific PA sensitive receptors exist in the brain. Our findings provide a clue to the elucidation of the presumed synaptic involvement of PA in the CNS. PMID- 6248170 TI - Angiotensin mimics the action of muscarinic agonists on rat sympathetic neurones. PMID- 6248171 TI - A re-evaluation of the mechanisms underlying simple cell orientation selectivity. AB - Following from evidence supporting GABA as a putative inhibitory transmitter in the visual cortex, we have iontophoretically applied the GABA antagonist N-methyl bicuculline (Nmb) to simple cells in order to block the inhibitory inputs acting on them. We found that under these conditions previously sharply-tuned simple cells responded equally to all orientations. Moreover receptive field dimensions, judged by the response to stimuli at the optimal and orthogonal orientations, equated best with that expected from a single dLGN cell input. It seems thus, that asymmetries in the excitatory input are not a significant factor in the generation of simple cell orientation selectivity. The asymmetry underlying orientation selectivity rather originates from the operation of an intracortical inhibitory mechanism. PMID- 6248172 TI - Evidence for involvement of separate mechanisms in the production of analgesia by electrical stimulation of the nucleus reticularis paragigantocellularis and nucleus raphe magnus in the rat. PMID- 6248173 TI - The effect of specific brain lesions on the high affinity binding of GABA in the substantia nigra. PMID- 6248174 TI - A topographic localization of enkephalin on the dopamine neurons of the rat substantia nigra and ventral tegmental area demonstrated by combined histofluorescence-immunocytochemistry. PMID- 6248175 TI - Effects of protein- and membrane-modifying agents on the binding of L [3H]glutamate to cerebellar synaptic membranes. PMID- 6248176 TI - [Effect of hormone administration on the onset and development of cardiac hypertrophy in rabbits (author's transl)]. PMID- 6248177 TI - Fine structure of fetal rat calvarium; provisional identification of preosteoclasts. AB - This is a study of the fine structure of cells of the 20-day fetal rat calvarium. Special attention is given to identifying and characterizing preosteoclasts. These cells are relatively common and located largely, but not exclusively, at the endocranial bone surface. The preosteoclasts are characterized by abundant mitochondria, an incomplete perinuclear Golgi apparatus, and variable-shaped dense granules. The dense granules are unique in appearance in that they contain an internal dense matrix surrounded by a clear halo. Most granules are circular in shape but some are elongate or tubular in form. Granules with identical appearance are observed in osteoclasts. The preosteoclasts are mononucleate, or occasionally binucleate. It is suggested that because preosteoclasts are morphologically distinctive dna relatively abundant, it should be feasible to separate these cells from a heterogeneous cell isolate. PMID- 6248178 TI - Collagenase and collagenase inhibitor levels following changes in bone resorption in vitro. PMID- 6248180 TI - Protein phosphorylation and the proliferation of chick embryo fibroblasts: analysis by in vitro phosphorylation using isolated plasma membranes and whole cell homogenates. AB - The relationship between plasma membrane and whole cell protein phosphorylation and chick embryo fibroblast proliferation was studied using an in vitro labeling technique employing [gamma-32P]ATP and isolated plasma membranes or whole cell homogenates. Cultures containing proliferating cells in log phase or containing cells stimulated to proliferate by the addition of serum were compared with cultures in which proliferation was inhibited due to cell density. Cell proliferation was found to be associated with increased plasma membrane basal protein kinase activity, but decreased membrane and whole cell cyclic AMP dependent kinase activity. The phosphorylation of a number of membrane and whole cell polypeptides differed between proliferating and density-inhibited cells, suggesting that these phosphoproteins may be involved in the regulatory events associated with cell proliferation. Of interest, however, was the fact that the phosphoprotein differences found with serum-stimulated and sparse, rapidly dividing cells were generally not the same. These observations suggest that the protein phosphorylation events associated with rapid proliferation of sparse, log phase cells may differ from those involved in serum-activated proliferation of quiescent cells. PMID- 6248179 TI - Effects of pyrophosphate and diphosphonates on the dissolution of hydroxyapatites using a flow system. AB - Pyrophosphate and diphosphonate ions have been said to diminish the dissolution of hydroxyapatite crystals, because they lower the equilibrium concentrations of calcium and phosphate ions in the bulk solution around hydroxyapatite crystals in a closed system. However, in a closed system these effects are not necessarily due to an effect on dissolution alone. In this paper we have used a continuous flow system to study the effects of pyrophosphate and two diphosphonates, ethane 1-hydroxy-1,1,-diphosphonate and dichloromethane diphosphonate, on the dissolution of hydroxyapatite. All three compounds decreased markedly the rate of dissolution of hydroxyapatite as well as the exchangeable pools of calcium and phosphate ions around the crystals. PMID- 6248181 TI - Inhibition of electron transport and oxidative phosphorylation in plant mitochondria by gladiolic acid and structurally-related aromatic ortho dialdehydes. AB - Gladiolic acid (GA, 4-methoxy-5-methyl-0-phthalaldehyde-3-carboxylic acid), an antifungal aromatic ortho dialdehyde produced by Penicillium gladioli was found to be a potent inhibitor of electron transport and oxidative phosphorylation reactions in sweet potato and mung bean mitochondria. Similar results were also found with the naturally occurring ortho dialdehydes, cyclopaldic acid, quadrilineatin, and flavipin as well as the synthetic dialdehydes, 3-formyl opianic acid and 0-phthalaldehyde. Because of their highly reactive ortho diformyl grouping, GA and structurally related dialdehydes apparently act as multisite inhibitors affecting electron transport and oxidative phosphorylation (at each coupling site). Gladiolic acid has no uncoupling effect like 2,4 dinitrophenol and does not have the same point of interaction in the energy transfer process as oligomycin. Several "partial" reactions of phosphorylation (Mg+2-DNP-stimulated ATPase; ATP-Pi exchange) were strongly inhibited by the various dialdehydes. Flavipin and quadrilineatin are potent inhibitors (80% at a concentration of 25 microM) of site III phosphorylation. Gladiolic acid and related ortho dialdehydes inactivate the catalytic activity of native cytochrome c in vitro. Lysyl epsilon-NH2 rich cytochrome c may be a major site of GA action in the intact mitochondrion. In view of the high chemical reactivity of the orthodiformyl group, it is suggested that mitochondrial function may be affected by aromatic ortho dialdehydes through a combination of reactions involving cross linking of amino groups on membrane polypeptides and monofunctional reaction with free amino groups important for enzyme function, including epsilon-NH2 groups on cytochrome c. Cross-linking in mitochondrial membrane systems might affect function by interfering with molecular motion in the operation of the terminal portion of the electron-transport chain. The primary toxicological mode of action of GA and related dialdehydes appears to be due to inhibition of mitochondrial function. PMID- 6248182 TI - Postmortem increases in GABA receptor binding to membranes of cat central nervous system. AB - GABA receptor binding in fifteen regions of cat central nervous system was investigated immediately postmortem and at twelve, twenty-four, and 72 hours postmortem. In each of the supraspinal areas studied, GABA binding increased with time-after-death. Changes after 24 hours occurred in the cerebellum, the visual cortex, the sensorimotor cortex, and the amygdala where more than a two-fold increase in binding was observed. Increases were also noted in the thalamus, caudate nucleus, hippocampus, and hypothalamus. The results suggest that caution should be exercised in the interpretation of GABA binding data obtained from human brains that have not been treated in a similar postmortem manner. PMID- 6248183 TI - Multicentricity of non-palpable breast cancer. AB - One hundred eighty-nine biopsies have been performed for clinically occult mammary lesions, detectable by mammography but not clinically apparent. Fifty-two cancers were demonstrated within this group, including 26 invasive ductal cancers, seven micro-invasive ductal cancers, 14 non-invasive ductal cancers, and five lobular carcinomas in situ. All mastectomy specimens were examined for multicentric foci of breast cancer in quadrants other than that in which the primary lesion was located. Of the invasive ductal cancers, 40% were multicentric. Of the micro-invasive ductal cancers, 57.1% were multicentric. Of the non-invasive ductal cancers, 45.5% were multicentric. The one mastectomy specimen from a patient with lobular carcinoma in situ did not have evidence of residual disease. The overall incidence of multicentricity in the 43 specimens examined was 44.2%. These findings suggested that any therapeutic procedure for either invasive or non-invasive ductal carcinoma that does not include total mastectomy may leave behind foci of cancer, which are a threat to the patient. PMID- 6248184 TI - Breast cancer patient's cell-mediated immune response to Thomsen-Friedenreich (T) antigen. AB - Thomsen-Friedenreich (T) antigenic specificity as determined with human serum anti-T was found in reactive form in breast adenocarcinomata but not in healthy and generally not in benign breast tissues. T-antigenic specificity was demonstrable in all metastatic breast carcinoma lesions. T specificity was also present in adeno- and squamous cell carcinomata from other organs; it was not found in the four melanomata, one glioblastoma, and seven benign non-breast tumors. Breast carcinoma patients but not healthy people showed cellular immunity to T antigen in vivo and in vitro. Most striking was the delayed-type cutaneous hypersensitivity reaction that was positive in over 85% of the ductal breast carcinoma patients tested, negative in over 94% benign breast disease patients, and in all presumably healthy individuals investigated. T antigen is readily available from healthy red blood cells in uncontaminated form, and free of HL-A and Australia antigens. PMID- 6248185 TI - The effects of exogenous estrogen replacement therapy of the breast: breast cancer risk and mammographic parenchymal patterns. AB - A retrospective pilot study was implemented to better define the potential carcinogenic role of conjugated equine estrogen (Premarin) on the breast, and the influence of these hormone analogues on proliferative and atrophic breast parenchyma as determined by high-quality serial xeromammograms. Four hundred and five postmenopausal (spontaneous and surgical) women (mean age 59.7 years) were group matched for the risk factors of age and parity. The dominant parenchymal pattern (N1P1P2DY) as disclosed mammographically was determined for each patient, who was then categorized into one of four groups: Group 1 Asymptomatic-no hormones, 124 patients; Group 2 Symptomatic-no hormones, 75 patients; Group 3 Asymptomatic-hormones; 152 patients; and Group 4 Symptomatic-hormones, 54 patients. Patients in Groups 3 and 4 were treated with therapeutic estrogens a minimum of 18 months (mean 79 months) and follow-up ranged from 39-344 months. In the entire series, 25 carcinomas (6.2%) were detected. In Group 3, five carcinomas (2.4%) were detected, but two cancers (1.0%) were found in symptomatic estrogen users. The occurrence of carcinoma in Group 2 was greater than the remaining categories; however, cancer risk was not statistically greater in any category with regard to hormone replacement therapy. Patients treated with therapeutic estrogens were observed to have an increase of 8.9% in the frequency of a more glandular (P2,DY) mammographic parenchymal pattern and this was noted to be within the range of interpretation error of the mammographer. This suggests a physiologic effect of therapeutic estrogens on atrophic breast parenchyma with conversion to a glandular, proliferative state. This study suggests that long term replacement estrogen therapy for postmenopausal symptoms does not significantly alter mammographic parenchymal patterns and that the use of these compounds in therapeutic doses does not increase the risk of breast cancer. PMID- 6248186 TI - Proliferation kinetics and cyclic AMP as prognostic factors in adult acute leukemia. AB - In 41 adult patients with acute leukemia (myeloblastic, lymphoblastic, and undifferentiated), proliferation kinetics (as determined by double-label autoradiography) and cyclic adenosine 3',5'-monophosphate (cAMP) concentration were studied for their significance in the prediction of responsiveness to cytostatic therapy. Patients with good clinical response had significantly shorter turnover times and higher labeling indices in the bone marrow than did those who failed to respond to treatment. Cases for which cell kinetics did not correlate with clinical response were explained by variance in the distribution of leukemic blasts between the proliferative cell cycle and the resting pool. Good clinical response was also found to be associated with low levels of cAMP in leukemic cells prior to therapy, whereas high cAMP contents predicted failure. Low cAMP concentrations, however, did not necessarily correlate with short turnover times and vice versa. This might be due to fluctuations of the cAMP concentrations during the cell cycle. PMID- 6248187 TI - Intracytoplasmic fibrillary inclusions in bronchial carcinoid. AB - A case of bronchial carcinoid with filamentous aggregates is described. The cytoplasmic inclusions were clearly demonstrated by means of Masson's trichrome stain in Bouin's fixed tissue, and the neoplastic cells showed a spontaneous green fluorescence with ultraviolet light. Electron microscopic examination showed that the inclusion bodies were composed of aggregates of filaments measuring 10A. They were located in the juxtanuclear region in close relation with mitochondria and the cisternae of the Golgi system. There were many neurosecretory granules inside the aggregates of filaments, some showing alterations in the dense core. From this data, we concluded that the aggregates seemed to represent an active rather than an involutional phenomenon and that their relation with hypoxemia and humoral influences needs further study. PMID- 6248188 TI - Granulofilamentous inclusions in a meningioma. AB - We have studied the histology, immunocytochemistry, and ultrastructure of a syncytial meningioma which contained the unusual feature of large eosinophilic intracytoplasmic inclusions. Electron microscopic examination revealed that these bodies were granular, osmiophilic masses, closely associated with cytoplasmic filaments of intermediate size. Desmosomal junctions with a somewhat abnormal morphology were also observed, and the possible relationship between the inclusions and the dense components of desmosomes is discussed. This tumor is also compared to other tumors of the central nervous system with hyaline and granulofilamentous inclusions. PMID- 6248189 TI - Hemorrhage from carcinoma of the lung. AB - During a retrospective analysis of 877 cases of lung cancer, we explored the relationships between cell type, site, cavitation, varying degrees of hemoptysis, and radiation therapy. Massive terminal hemoptysis (29 cases) was found to be significantly associated with cavitated (P less than 0.0001 squamous cell carcinoma (P = 0.0002), ARISING IN EITHER THE RIGHT OR LEFT MAIN BRONCHI (P less than 0.0001). Lesser, nonlethal degrees of hemoptysis (140 cases) were not cell type associated, occurring in approximately 15% of cases of all major tumor types. Radiotherapy, although employed more frequently in the massive-hemoptysis population, did not appear to be causally related to hemoptysis of any degree. An interesting case, which provoked the above study, is described: a patient with bronchogenic squamous cell carcinoma and terminal hemoptysis due to a tumor fistula between the primary lesion and the left atrial chamber. The forms of cardiac involvement in lung cancer are discussed. PMID- 6248190 TI - Characterization of tumor-specific DNA sequences: molecular grading of the astrocytomas. AB - Tumor-specific DNA sequences or unique sequences have been found in a number of human cancer cells including gliomas but not in equivalent normal cells. In a continuing effort to further elucidate the nature of these sequences, thermal analysis using the hydroxyapatite technique was carried out on the various grades of astrocytomas. A recycled DNA molecular probe from Grade IV astrocytomas was annealed to the various grades of astrocytoma DNAs and to normal brain DNA which served as control. There was an increasing percentage of hybridization in direct proportion to the degree of malignancy. The same results were obtained using a recycled DNA probe from medulloblastomas. Thermal melt analysis of these same tumors revealed a Tm (melting temperature or temperature of reassociation) of about 83 degrees C, irrespective of degree or grade of malignancy. These results would indicate that the type of genetic DNA sequences or tumor-specific DNA sequences involved in this type of tumor is the same, whether the tumor is benign or malignant. The demonstration of the increasing percentage of hybridization based on the increasing degree or grade of malignancy and the further demonstration that the involved tumor-specific DNA sequences are the same irrespective of the degree of malignancy, justify the conclusion that the number of copies of these sequences determines the degree or grade of malignancy. Pending further laboratory confirmation, this fact may be assumed to be true with respect to cancers from other organ sites. PMID- 6248191 TI - Primary hepatic malignant lymphoma: its occurrence in a patient with chronic active hepatitis, cirrhosis, and hepatocellular carcinoma associated with hepatitis B viral infection. AB - A patient with hepatitis B induced chronic active hepatitis and cirrhosis had hepatocellular carcinoma and poorly differentiated lymphocytic malignant lymphoma localized in the liver. Whereas a close relationship between hepatitis B viral infection, chronic active hepatitis, macronodular cirrhosis, and hepatocellular carcinoma is now recognized, no such association has been reported with primary hepatic malignant lymphoma, which is a distinctly rare entity. In a large autopsy population that we reviewed systemic malignant lymphoma rarely occurred in association with cirrhosis. Such an association has been noted in other studies, however. We speculate half if an association exists between malignant lymphoma and cirrhosis it might have an immunologic basis such as seen in certain autoimmune diseases. PMID- 6248192 TI - Ectopic hormones in lung cancer patients at diagnosis and during therapy. AB - In roughly 10 patients with lung cancer of various histologic types, the levels of hormones adrenocorticotropin (ACTH), calcitonin, parathormone, beta choriogonadotropin (HCG), human placental lactogen (HPL), growth hormone (HGH), and prolactin were determined by radioimmunoassay. The ACTH level was elevated in 30% of patients with oat cell carcinoma and in 26% of patients with large cell carcinoma. Calcitonin levels were increased in 48% of patients with oat cell carcinoma. Elevated levels of HCG were found in 33% of patients with oat cell carcinoma, in 26% of patients with large cell carcinoma, and in 19% of patients with squamous cell carcinoma. Parathormone was increased in 32% of patients with squamous cell carcinoma in 27% of patients with oat cell carcinoma, and in a few patients with large cell carcinoma. Prolactin, HCG and HPL were present only in single cases. Elevated levels of at least one hormone were found in 65.2% of all patients, and in 78% of the patients with oat cell carcinoma. Serial determinations of ACTH and calcitonin showed that these hormones are useful for monitoring therapy in lung patients. There was no relation between hormone levels and the clinical stage of disease. PMID- 6248193 TI - The histopathological evaluation of human breast cancers in correlation with estrogen receptor values. AB - A detailed histopathological review of 140 primary breast cancers analyzed for estrogen receptor protein (ERP) was carried out and a variety of morphological features correlated with ERP results. ERP in cytosols was incubated with [3H]estradiol in the presence and absence of cold estradiol and assayed by agargel electrophoresis. Tumors binding greater than 10 fmol estradiol/mg tissue protein were classified as receptor-positive. Seventy-seven percent of the 116 infiltrating duct carcinomas were ERP-positive. The well-differentiated tumors of this group had a higher incidence of ERP-positivity than the poorly differentiated ones. The ten predominantly or exclusively intraductal carcinomas and the seven medullary tumors were less frequently positive than the main group of infiltrating ductal cancers. The three colloid, two tubular, and two lobular carcinomas in this series were all ERP-positive. When receptor measurements are evaluated, consideration should be given to the degree of differentiation and the histological type of tumor, in addition to other factors known to influence receptor levels such as menopausal status and seasonal variation. PMID- 6248194 TI - Fibrolamellar carcinoma of the liver: a tumor of adolescents and young adults with distinctive clinico-pathologic features. AB - Clinical and pathologic features of 23 patients with a distinctive histologic and clinical variant of hepatocellular carcinoma are summarized. The variant pattern of hepatocellular carcinoma is most common in the age group 5--35 years and occurs equally in either sex. The distinctive histologic features include 1) deeply eosinophilic neoplastic hepatocytes, many of which contain intracytoplasmic hyaline globules and distinct pale bodies and 2) fibrosis arranged in a lamellar fashion around the neoplastic hepatocytes. The histologic and gross features of the tumor have been confused both with focal nodular hyperplasia and with hepatocellular adenoma. The average survival of 32 months and the high operability rate of 48% far exceed the survival or operability for ordinary hepatocellular carcinoma. Thus, this tumor type must be recognized and considered separately when evaluating therapeutic results in large series of patients with hepatocellular carcinoma. PMID- 6248195 TI - Primary sarcoma of the aorta associated with a vascular prosthesis: a case report. AB - A case of a primary malignant fibrous histiocytoma of the aorta, arising at the site of a woven Dacron thoracic aortic graft is described. Hypertension was a prominent clinical feature. Compression and distortion of the aortic graft by tumor complicated later surgical repair of an adjacent aortic aneurysm, resulting in death. At autopsy, the tumor was shown to have arisen in a portion of aortic wall surrounding the graft material. Tumor emboli were present in several distal arteries, with complete occlusion of the right renal artery by invasive tumor embolus. Primary tumors of the aorta are rare; 16 such cases have been reported in the literature. Only 2 previous cases of tumors associated with vascular prostheses have been reported. The occurrence of tumor in this case adjacent to an aortic graft raises the possibility that the graft material played a role in tumor induction. PMID- 6248196 TI - Colorectal cancer in Jordan and Nova Scotia: a comparative epidemiologic and histopathologic study. AB - A comparative study of colorectal adenocarcinoma was undertaken among the populations of Jordan and Nova Scotia, Canada. The incidence of this cancer was 13 (colon 6, rectum 7) and 53 (colon 31, rectum 22) per 100,000 males aged 35--64 years, respectively. Colonic tumors (excluding rectosigmoid) showed left-sided preponderance in Jordanians and right-sided preponderance in Nova Scotians. Age average at diagnosis was 49 years in Jordanians (colon 47 years and rectum 50 years) and 66 years in Nova Scotians (colon 67 years and rectum 63 years), with peaks in the fifth and seventh decades and a male to female ratio of 1.3:1 and 1:1, respectively. The mucinous type accounted for 31 and 13% of colorectal adenocarcinomas in Jordanians and Nova Scotians, respectively, of which the signet-cell type accounted for 14 and 2% of the total number, respectively. The actual incidence rate of mucinous carcinoma, however, was higher among Nova Scotians. In both groups, mucinous carcinoma showed predilection for females and rectal signet-cell carcinoma showed bias toward younger females. The authors believe that the significantly different epidemiologic and morphologic features of colorectal cancer demonstrated in these two communities could shed light on possible etiologic influences, such as dietary habits or other environmental factors. PMID- 6248197 TI - Colony growth in soft agar of human melanoma, sarcoma, and lung carcinoma cells disaggregated by mechanical and enzymatic methods. AB - The effect of mechanical and enzymatic disaggregation on human malignant melanoma, soft-tissue sarcoma and lung carcinoma colony growth in soft agar was studied. The enzymatic disaggregation was advantageous in most cases of melanoma and sarcoma, giving a larger number of colonies and increasing the probability of achieving growth in soft agar. Enzymatically treated pulmonary carcinoma cell populations had lower clonogeneic potential, especially in the case of anaplastic carcinomas. Morphological studies showed that the cells growing in soft-agar colonies had the same characteristics as those of the original tumor. A linear relationship was obtained between the number of enzymatically and mechanically treated tumor cells plated and the number of colonies. Delayed plating decreased the number of colonies. PMID- 6248198 TI - Synergistic antileukemic effect of theophylline and 1,3-bis(2-chloroethyl)-1 nitrosourea. AB - A series of experiments evaluated the antileukemic effect of an agent which elevates cellular cyclic adenosine 3':5'-monophosphate levels by phosphate levels by inhibiting phosphodiesterase. When administered alone, theophylline had only modest antileukemic effects, but it had synergistic effects when administered with 1,3-bis(2-chloroethyl)-1-nitrosourea. This synergism produced an improved therapeutic index in a dose-response study and in a comparison between antileukemic effects and effects on white blood cell nadirs. Uptake of 1,3-bis(2 chloroethyl)-1-nitrosourea and studies of timing of treatment support the hypothesis that elevation of cyclic adenosine 3':5'-monophosphate levels is the mechanism of the observed synergistic effect. PMID- 6248199 TI - Comparison of properties of mouse cells transformed spontaneously by ultraviolet light-irradiated herpes simplex virus or by simian virus 40. PMID- 6248200 TI - Effect of subcutaneously administered 2,6,10,14-tetramethylpentadecane on plasmacytoma growth. AB - 2,6,10,14-Tetramethylpentadecane (pristane), s.c. injected simultaneously with plasmacytoma inocula, enhances the transplantability of tumor cells. The effect is dose and time dependent. The enhancement is shown only by plasmacytoma (MOPC 315 and MPC-11) and not by the murine lymphosarcoma and chondrosarcoma tested. Various mechanisms, such as stress and depression of humoral and cellular immunity, have been considered. PMID- 6248201 TI - Glucocorticoid receptors in peripheral blood lymphocytes from bovine leukemia virus-infected cows with persistent lymphocytosis. AB - Bovine leukemia virus-infected cows with persistent lymphocytosis have an expanded population of B-lymphocytes in the peripheral blood that is sensitive to glucocorticoids in vitro and in vivo. We examined peripheral blood lymphocytes from cows with persistent lymphocytosis for the presence of specific glucocorticoid receptors. Steroid binding in intact cells was determined by a whole cell competitive binding assay using [3H]dexamethasone. The binding of the glucocorticoid to receptor was characterized in terms of affinity, specificity, and kinetics of the reaction. We found that peripheral blood lymphocytes from three cows with persistent lymphocytosis had 5000 to 6600 specific glucocorticoid binding sites/cell. Compared with that reported for human lymphoid cells, glucocorticoid receptors in the bovine lymphocytes were found to have a greater affinity for the steroid with an association rate that was three times faster and a dissociation rate that was less than one-half of the former. We examined the biological half-life of hydrocortisone in the normal cow and found it to be 69.3 min, which is shorter than that reported for other domestic species and humans. The kinetics and affinity of the steroid binding may explain why in vivo glucocorticoid sensitivity was demonstrated in these animals despite the fact that elevated levels of plasma corticoids were not maintained. These results suggest that glucocorticoid sensitivity may be influenced by the nature of the binding reaction between steroid and receptor. PMID- 6248202 TI - Uridine kinase, adenylate kinase, and guanase in human lung tumors. AB - In pulmonary neoplasms, the uridine kinase concentration was higher (2- to 20 fold) than in the noninvolved lung portions of each of the 12 subjects studied. The extent of elevation of uridine kinase in the different tumors showed a significant positive correlation with the rises (1.5- to 30-fold) in thymidine kinase, suggesting that neoplastic transformation in human lung involved coordinated increases in the capacity for the reutilization of different nucleoside phosphates. Adenylate kinase was always at lower levels in neoplasms compared to noninvolved areas of the same lung, and the extent of this loss in the different tumors correlated inversely with the gain in uridine kinase and thymidine kinase. Normal fetal human lung was also deficient in adenylate kinase, while its uridine kinase and thymidine kinase (and also guanase) activities were above the adult levels. The guanase activities of the different neoplasms, unrelated to their uridine kinase or thymidine kinase content, correlated with the activities in the subjects' noninvolved lung. These individual differences were much more striking than those between the neoplastic and control samples. Variations in guanase activity thus appear to be "random," whereas observations on the three other enzymes attest to the orderly nature of biochemical differences among individual tumors and between normal and neoplastic lung. PMID- 6248203 TI - Correlation between the detection of specific mouse mammary tumor proviral sequences and the presence of pulmonary metastases in mice bearing spontaneous mammary tumors. AB - Pulmonary metastases in C3H/He mice bearing spontaneous mammary tumors were detected and characterized by histological criteria and immunocytochemical staining for mouse mammary tumor virus antigens. The same lungs containing metastases were also positive when assayed for a specific subset of mouse mammary tumor virus proviral DNA sequences. These sequences, termed tumor-associated sequences, have previously been shown to be present in the DNA of spontaneous mammary tumors that arise before 1 yr of age in C3H/He mice but are absent in DNA's of apparently normal tissues of C3H/He mice. Reconstruction experiments demonstrated that the nucleic acid hybridization method will detect at least one mammary tumor cell/250 cells. While DNA from 13 lungs of apparently normal C3H/He mice did not contain sequences homologous to mouse mammary tumor virus tumor associated-sequence RNA, DNA from lungs of 9 of 12 C3H/He mice bearing spontaneous mammary tumors did contain these sequences. Since the entire DNA content of the lung can be assayed as one sample, the hybridization method minimizes false negatives resulting from histological analysis of random biopsy sampling. The hybridization procedure described here thus represents a sensitive and quantitative element as an adjunct for the detection of micrometastatic lesions in mice bearing viral-mediated spontaneous mammary carcinomas. PMID- 6248204 TI - Comparative responses of normal and malignant mouse mammary cells to modulation of surface properties. AB - We previously demonstrated that epithelial cells growing in primary cultures derived from normal and neoplastic mouse mammary tissues are indistinguishable on the basis of morphology, surface topography, agglutinability by concanavalin A, or of number, cytoplasmic location, or organization of microtubules and actin containing microfilaments. In the present study, the modulation and interrelationships of these features were investigated using the drugs colchicine and cytochalasin B and the enzymes trypsin, collagenase, and hyaluronidase. Untreated cells of both types were only weakly agglutinable by concanavalin A. Pretreatment of the cells with colchicine, cytochalasin B, or hyaluronidase increased cytoagglutination by the lectin dramatically, whereas neither trypsin nor collagenase significantly altered reactivity of the cells. Binding studies utilizing fluorescein-tagged concanavalin A indicated that the enhanced agglutinability did not correlate with any particular distribution of lectin receptors on the cells. At the doses used, colchicine and cytocholasin B induced disruption of microtubules and microfilament networks, respectively, but no effects on either type of cytoskeletal element were observed after hyaluronidase, trypsin, or collagenase. The increased agglutinability was not associated with any specific surface conformation since scanning electron microscopy revealed that untreated cells and cells exposed to colchicine, hyaluronidase, and collagenase were flat and possessed variable numbers of small microvilli. In contrast, following incubation with cytochalasin B or trypsin, the cells underwent retraction and rounding, and developed complex surface structures such as blebs, ruffles, and filopodia. Thus, no single factor appeared responsible for determining the agglutinable or nonagglutinable state of the mammary cells. Morover, no differences were detected in the surface responses of the normal and malignant cells under any of the conditions used. PMID- 6248206 TI - Vasoactive intestinal peptide control of cyclic adenosine 3':5'-monophosphate levels in seven human colorectal adenocarcinoma cell lines in culture. AB - This study was undertaken to assess the role of vasoactive intestinal peptide (VIP) in the control of cyclic adenosine 3':5'-monophosphate production in colonic tumor cells. Seven human colorectal adenocarcinoma cell lines in culture were investigated (HT-29, HRT-18, SW-480, Caco-2, CO-115, CO-125, and HCT-8R). These cell-lines had a cyclic adenosine 3':5'-monophosphate production system which was very sensitive to VIP but less so to prostaglandin E1 and/or isoproterenol. Nonintestinal human malignant epithelial cells, such as HeLa (cervix) and Caki-1 and Caki-2 (kidney), by contrast, did not respond to VIP. The dose-response relationships of malignant colorectal cells were compared to those obtained with epithelial cells of normal human colon and showed that: (a) maximal responses were observed with 0.1 micro M VIP in both malignant and normal cells; (b) half-maximal responses were elicited by VIP concentrations in the 0.3 to 2 nM range in malignant cells (1.2 nM in normal cells), thus indicating the high apparent affinity of the cells to VIP; and (c) the magnitudes of the responses (stimulated:basal ratios) were highly variable in malignant cells, ranging from 225 in HT-29 cells to 3.5 in Caco-2 cells, but were more constant, in the order of 25, in normal cells. Secretin, a VIP agonist in intestinal tissue, stimulated cyclic adenosine 3':5'-monophosphate accumulation in all colorectal cells, but with a 1000- to 5000-fold lower potency than did VIP. These results show that the VIP-sensitive adenylate cyclase system operates in malignant as well as in normal colon epithelial cells. PMID- 6248205 TI - Effects of tetrahydrouridine on the uptake and metabolism of 1-beta-D arabinofuranosylcytosine in human normal and leukemic cells. PMID- 6248207 TI - Isolation of an inhibitor of type II interferon induction from tumor ascitic fluids. AB - A low-molecular-weight fraction (M.W. approximately 700) that specifically impairs the induction of type II interferon in mice by purified protein derivative of tuberculin or OK-432 was isolated from the cell-free ascitic fluid of mice bearing Ehrlich ascites carcinoma. Purification was achieved by ultrafiltration and gel filtration. The inhibitory activity of the isolated fraction was 10 times greater than that of the unfractionated starting material in the impairment of type II interferon induction. The significant inhibition was observed even when 0.2 ml of the 10,000-fold dilution of the fraction, which was previously adjusted to 0.25 A unit at 290 nm absorption, was once treated i.p. in normal mice 48 hr before challenge of type II interferon inducers. This fraction was stable to heating at 56 degrees for 60 min. The active component, however, did not affect the in vivo induction of type I interferon by polyriboinosinic polyribocytidylic acid or tilorone-HCl. In parallel experiments, an identical low molecular-weight fraction that impairs the type II interferon induction in mice was isolated from the ascitic fluids of rats bearing AH-100B ascites tumor and from a human hepatoma case with advanced cancer metastatic to the peritoneal cavity. However, nontumorous ascitic fluids obtained from adjuvant-stimulated mice and a human liver cirrhosis case did not contain any such inhibitory activity. PMID- 6248208 TI - Estrogen, androgen, glucocorticoid, and progesterone receptors in progestin induced regression of human breast cancer. AB - A study was made of basic mechanisms involved in regression of breast cancer exposed to high levels of synthetic progestins. The possibility that progestins act on breast cancer by way of the progesterone receptor mechanism and subsequent increase of estradiol 17 beta-dehydrogenase activity could not be confirmed in this investigation. It is demonstrated that the progestins megestrol acetate and medroxyprogesterone acetate are strong competitors for steroids which bind specifically to androgen, glucocorticoid, and progesterone receptors, indicating that the progestins are able to bind to these receptors with high affinity. In contrast, these progestins do not compete with estradiol for estrogen receptor binding. In 34 patients with progressive metastatic breast cancer, results of receptor studies have been correlated with clinical response during treatment with megestrol acetate. Statistically, regressions were significantly associated with tumors containing large amounts of androgen receptors. Clinical correlation with the quantities of glucocorticoid receptor was weak, while such correlations with estrogen and progesterone receptors were absent. However, we did demonstrate relationships between the quantities of the various receptors in breast cancer. Tumors containing a large amount of androgen receptors also generally contain estrogen receptors. It might be that a favorable response to progestins is confined to the group of patients with hormone-responsive breast cancers, as such characterized by the presence of estrogen receptors, and that within this group the actual androgen receptor levels determine response. PMID- 6248209 TI - Selective inhibition by benzaldehyde of the uptake of nucleosides and sugar into simian virus 40-transformed cells. AB - The effects of benzaldehyde, which has been found in figs as a carcinostatic element, were studied on the uptake of nucleosides, 2-deoxy-D-glucose, and amino acids into simian virus 40-transformed rat fibroblast cells (SV40-transformed cells) and into the parent normal cells (normal cells). Benzaldehyde, at the concentrations of 25 to 100 microgram/ml at which the selective growth inhibition against SV40-transformed cells was revealed, markedly inhibited the uptake of thymidine, other nucleosides, and 2-deoxy-D-glucose into SV40-transformed cells without any significant inhibition of the uptake of these compounds into normal cells. The uptake of amino acids into both transformed and normal cells was not inhibited by benzaldehyde. Selectively cytotoxic benzaldehyde-related compounds such as 4-nitrobenzaldehyde, 4-acetaminobenzaldehyde, thiophene-3-carboxaldehyde, etc., showed a similar inhibitory effect on thymidine uptake. The deprivation of glucose from the incubation medium strikingly diminished the inhibitory effect of benzaldehyde on the uptake of thymidine and 2-deoxy-D-glucose into SV40 transformed cells. The intracellular adenosine 5'-triphosphate level of SV40 transformed cells was reduced to less than one-half by treatment with benzaldehyde (50 microgram/ml) in glucose-containing medium. This effect was not observed in glucose-free medium. Treatment with benzaldehyde caused no change of the intracellular adenosine 5'-triphosphate level of normal cells. Based on the above results, the selective cytotoxicity of benzaldehyde was attributed to the reduction of intracellular adenosine 5'-triphosphate level of transformed cells, accompanied by the poor uptake of thymidine, glucose, etc., into SV40-transformed cells. PMID- 6248210 TI - A double-blind study on the effects of differing purified cellulose and pectin fiber diets on 1,2-dimethylhydrazine-induced rat colonic neoplasia. AB - The incidence, distribution, size, and histopathology of colonic tumors induced by parenteral administration of 1,2-dimethylhydrazine were examined in rats fed a chemically defined fiber-free diet or nutritionally and calorically equivalent diets containing either 4.5 or 9.0% purified cellulose or pectin. This double blind study indicates that cellulose is protective against experimental colonic neoplasia. Although the precise mechanism for this protective effect remains to be elucidated, it was not cellulose dose dependent and appeared to depend on administration during injection of carcinogen. Furthermore, this study provides strong evidence that identical amounts of cellulose and pectin fed as the sole source of fiber in chemically defined diets exert strikingly different effects in relation to development of intestinal neoplasia in this animal model. PMID- 6248211 TI - Comparative effects of vindesine, vinblastine, and vincristine on mitotic arrest and hormonal response of L1210 leukemia cells. AB - The Vinca alkaloids vinblastine, vincristine, and vindesine were compared for their capacity to arrest L1210 cells in mitosis and for their effect on the response of L1210 cells to beta-adrenergic and prostaglandin E1 hormones. Both microscopic and flow cytofluorimetric studies showed that, of the three drugs, vindesine was the most potent for inhibiting growth and arresting L1210 cells in mitosis. In the hormone response studies, vindesine was also found to be the most potent of the three drugs. Cells pretreated for 30 min with 10(-6) M concentrations of the drugs increased the initial hormone response after 5 min of L1210 cells to either hormone by 100%. After a 1-hr exposure to either isoproterenol or prostaglandin E1, however, the vindesine-treated cells had cyclic adenosine 3':5'-monophosphate levels several times higher than did controls. Vinblastine- and vincristine-treated cells were not different from the controls after 1 hr of hormone exposure. Dose-response studies show that the vindesine effect on enhanced cyclic adenosine 3':5'-monophosphate accumulation increases substantially with drug concentrations from 10(-8) to 10(-5) M. These and other studies indicate that the effect of the Vinca alkaloids on cyclic adenosine 3':5'-monophosphate metabolism occurs at the transduction mechanism which couples the hormone receptor to the catalytic component of the adenylate cyclase complex. PMID- 6248212 TI - Variation of activity of protein kinases in unstimulated and phytohemagglutinin stimulated normal and leukemic human lymphocytes. AB - Cyclic adenosine 3':5'-monophosphate-dependent protein kinase (kinase A) and cyclic guanosine 3':5'-monophosphate-dependent protein kinase (kinase G) were assayed in lymphocytes of normal subjects, adults with chronic lymphocytic leukemia (CLL), and children with acute lymphocytic leukemia (ALL). There was a good correlation between the activity of the two kinases and the level of the corresponding cyclic nucleotides. This was true for cultured phytohemagglutinin stimulated normal lymphocytes and CLL lymphocytes as well. Kinase A activity was low and kinase G activity was high in leukemic cells in the absence of the respective cyclic nucleotides [5 and 8 units (pmol 32P incorporated into histone per min per mg protein) for kinase A and 98 and 51 units for kinase G in ALL and CLL lymphocytes, respectively]. Upon addition of cyclic adenosine 3':5' monophosphate and cyclic guanosine 3':5'-monophosphate in vitro, values for kinase A activity returned to normal (approximately 30 units), whereas those for kinase G increased further (212 units for ALL and 85 units for CLL lymphocytes; 22 units was the kinase activity for normal lymphocytes). These findings suggest that cyclic nucleotides achieve thetr specificity in the regulation of the cell, in part, through the activation of the dependent protein kinases and that both kinase A and kinase G may be functionally intact in leukemic cells. PMID- 6248213 TI - Modulation of the cytotoxic response against allogeneic tumor cells in culture by adriamycin. PMID- 6248214 TI - Inhibition of chemically induced morphological transformation and reversion of the transformed phenotype of ascorbic acid in C3H/10T 1/2 cells. PMID- 6248215 TI - Defective cyclic adenosine 3'-5'-monophosphate-dependent phosphorylation of plasma membrane proteins in chemically and virally transformed cells. AB - Cyclic adenosine 3':5'-monophosphate (cyclic AMP)-dependent phosphorylation of endogenous plasma membrane proteins catalyzed by an endogenous plasma membrane protein kinase was assayed in purified plasma membrane preparations derived from nontransformed, methylcholanthrene-transformed, and simian virus 40 (SV40) transformed BALB/3T3 cells. In nontransformed cells, cyclic AMP stimulated the phosphorylation of two proteins with molecular weights of 24,000 and 14,000. The labeling of these proteins could be inhibited by rabbit skeletal muscle protein kinase inhibitor. In methylcholanthrene-transformed cells, no cyclic AMP dependent phosphorylation of endogenous plasma membrane proteins was observed. SV40-transformed cells also showed markedly decreased cyclic AMP-dependent phosphorylation of both endogenous plasma membrane substrates. Addition of exogenous cyclic AMP-dependent protein kinase from bovine kidney to plasma membrane preparations isolated from methylcholanthrene or SV40-transformed isolated from methylcholanthrene or SV40-transformed cells, however, catalyzed the cyclic AMP-dependent phosphorylation of both the M.W. 24,000 and M.W. 14,000 substrates. These data show that the plasma membranes of transformed cells have a defect in an endogenous cyclic AMP-dependent phosphorylation system and that this defect can be corrected by addition of an exogenous cyclic AMP-dependent protein kinase. PMID- 6248216 TI - Cyclic adenosine 3':5'-monophosphate-binding protein, a biochemical marker of neuroblastoma differentiation. AB - Mouse neuroblastoma tumors show reduced amounts of cyclic adenosine 3':5' monophosphate (cAMP) binding protein. However, the levels of cAMP-binding protein were increased by 2-fold when the tumor cells were established in tissue culture, and these levels were comparable to that found in mouse brain. This binding protein is a free cAMP-binding protein that is not associated with protein kinase. The reduced amounts of free cAMP-binding protein in tumors are not a consequence of a defective gene, but the synthesis of this protein is regulated at the transcriptional and/or translational levels. The free cAMP-binding protein like the neurotransmitter-synthesizing enzymes can be used as a biochemical marker of differentiation, and this protein may play a role in neuronal differentiation. PMID- 6248217 TI - Specific immunodiagnosis of hepatoma by tube leukocyte adherence inhibition assay and a modified method of repeated tube leukocyte adherence inhibition assay. AB - Tube leukocyte adherence inhibition (LAI) assays were performed with normal liver extract as nonspecific antigen and with hepatoma extract as specific antigen in patients with hepatoma. Titration experiments revealed that the optimal extract concentration was 400 micrograms/ml when expressing the results in terms of a nonadherence index. The results of tube LAI assays were positive in 26 of 40 cases (65%) of hepatoma. The results were negative in all cases of other liver diseases and other cancers. The tube LAI assay was repeated after discarding the non-adherent cells in the initial tube LAI assay with normal liver extract. The nonadherence index of the repeated tube LAI assay we devised was significantly higher than that of the original tube LAI assay (p less than 0.001) in patients with hepatoma. Ten of 12 patients with hepatoma in whom the results of the original tube LAI assay were negative showed positive results in the repeated tube LAI assay. The present study suggests that the problem of false-negative results in tube LAI assay can be solved by repeating the tube LAI assay. PMID- 6248218 TI - Myocardial metabolic changes related to ventricular fibrillation. AB - The cause of death in patients who die suddenly or after an acute myocardial infarction is, in most cases, ventricular fibrillation. Most of these patients suffer from ischemic heart disease and atherosclerotic narrowing of the coronary arteries. Ischemic changes include hypoxia, accumulation of metabolites, depletion of energy-yielding substrates, ionic shifts and structural changes. There is an increased sympathetic activity and often a higher vagal tone. Recent observations support the idea that there is an elevated regional adrenergic activity in the ischemic area with increased tissue levels of cyclic AMP. This seems to be one of several important factors contributing to the occurrence of ventricular fibrillation. Increased sympathetic activity might mediate reentry mechanisms as well as enhanced automaticity. PMID- 6248219 TI - In vitro efficacy of cefoperazone compared with cefotaxime, LY127935, and thienamycin. PMID- 6248220 TI - Activities of cefoperazone, cefotaxime, cefuroxime, and cephalothin against 128 clinical isolates. PMID- 6248221 TI - Comparative pharmacokinetics of cefoperazone and cefotaxime. AB - The pharmacokinetics of cefoperazone and cefotaxime were compared in a crossover, randomized study in ten healthy volunteers (5 males, 5 females). Each subject received 2.0 gm of the study drug administered by an IV infusion over 30 minutes. Serum concentrations of cefoperazone and cefotaxime at the end of the infusion (zero time) were 254 mg/liter and 144 mg/liter, respectively. Comparative results at other times were the following: four hours, 20 mg/liter and 3 mg/liter; eight hours, 4.4 mg/liter and 0.3 mg/liter; and 12 hours, 1.2 mg/liter and 0.0 mg/liter. Twenty-one percent of the 2.0-gm single dose of cefoperazone was recovered in the urine during the first 24 hours following dosing, compared to 52% for cefotaxime. The renal clearance of cefoperazone was also determined in three patients during four hours. The results of the investigations will be discussed in view of the clinical relevance. PMID- 6248222 TI - ATP-A activity in cultured human glioma cells. PMID- 6248223 TI - Regulation of a novel autophosphorylating protein kinase by adrenocortical carcinoma--a review. PMID- 6248224 TI - The evaluation of electron microscopic cytochrome-oxidase reaction in experimental heart muscle hypoxia. PMID- 6248225 TI - [Ascorbic acid in relation to cyclic neucleotides (author's transl)]. PMID- 6248226 TI - Mechanism of the ultrastructural changes induced by partial hepatectomy in the STH cells of mice. AB - The ultrastructural changes induced by partial hepatectomy in the STH cells of mice were examined. These changes suggest an increased secretory activity of STH cells. Therefore, several experimental procedures elucidating the possible mechanism of this effect were undertaken. Normal mice were starved for 52 h or treated with insulin, glucagon, or cAMP. Serum glucose level measurements as well as electron microscopy of pituitary STH cells were carried out in each group of animals. It was found that STH cells of glucagon- and cAMP-treated mice showed some of the ultrastructural features observed in partially hepatectomized animals. Hence, serum hyperglucagonemia and increase in pituitary cAMP content, may be important components of the complex mechanism responsible for the ultrastructural changes in STH cells brought about by partial hepatectomy. PMID- 6248227 TI - Presence of adrenocorticotropin and beta-endorphin immunoreactivities in the magnocellular neurosecretory system of the rat hypothalamus. PMID- 6248228 TI - Fibre types in the locomotory muscles of an Antarctic teleost, notothenia rossii. A histochemical ultrastructural and biochemical study. AB - The metabolic and structural differentiation of locomotory muscles of Notothenia rossii has been investigated. In this species sustained locomotion is achieved by sculling with enlarged pectoral fins (labriform locomotion), whilst the segmental myotomal muscle is reserved for burst activity. Red, white and subepidermal fibres can be distinguished in the trunk by histochemical and ultrastructural criteria. The main pectoral muscle (m. adductor profundus) consists entirely of red fibres. These three main fibres types show differences in histochemical staining profiles, capillarization, myofibril shape and packing, and lipid and mitochondrial content. The fractional volume of mitochondria amounts to 38% for pectoral, 30% for red myotomal and 1.9% for white myotomal fibres. Enzyme activities of red pectoral muscle are consistent with a higher potential for aerobic glucose and fatty acid oxidation than for the red myotomal fibres. Mg2+ Ca2+-myofibrillar ATPase activities are similar for red pectoral and myotomal muscles and approximately half of those white fibres. Specialisations of N. rossi muscles associated with labriform swimming and locomotion at Antarctic temperatures are discussed. PMID- 6248230 TI - Characterization of two xenopus somatic 5S DNAs and one minor oocyte-specific 5S DNA. AB - The somatic 5S DNA from X. borealis (Xbs 5S DNA) and X. laevis (Xis 5S DNA) and a minor oocyte-specific 5S DNA from X. laevis (Xit 5S DNA) have been purified, and individual repeating units have been cloned and sequenced. The two somatic 5S DNAs differ from the major oocyte 5S DNAs in having GC-rich spacers, homogeneous repeat lengths and no "pseudogenes." The somatic 5S DNAs from the two species have similar spacer sequences with differences due to single base changes and insertions/deletions. The spacer of the minor oocyte-specific 5S DNA (Xit) has the AT-rich sequence characteristic of the major oocyte 5S DNAs from X. laevis and X. borealis, and contains one duplication that has diverged approximately 40%. Like the somatic 5S DNAs, Xit 5S DNA has a homogeneous length repeat and a unique nucleotide sequence in its spacer. The presence of variable-length spacer regions in a multigene family correlates with variables numbers of a simple sequence in the spacer regions. PMID- 6248229 TI - The distribution and structure of cells in the tracheal epithelium of the mouse. AB - The tracheal epithelium of the mouse is a single layer of columnar cells resting on a basement membrane. Many of the cell types resemble those of other species. However, goblet cells are rare and ciliated cells occur only in scattered patches. Submucosal glands are absent from all but the highest reaches of the airway. The major proportion of the epithelial cells are non-ciliated. These usually project into the lumen of the trachea. Large amounts of smooth endoplasmic reticulum and many secretory vesicles occur within the cytoplasm. Secretory activity of these cells may be either apocrine or merocrine and these cells may transform into other cell types. It is suggested that these non ciliated cells are Clara cells and that the mouse tracheal epithelium may make a useful model for the study of this type of cell. PMID- 6248231 TI - Integration and excision of SV40 DNA from the chromosome of a transformed cell. PMID- 6248232 TI - Mosaic organization of a mitochondrial gene: evidence from double mutants in the cytochrome b region of Saccharomyces cerevisiae. AB - The region coding for apocytochrome b in the mitochondrial genome of Saccharomyces cerevisiae is believed to exhibit a mosaic organization, consisting in certain strains of five exons and four introns. This model can be tested by the use of double mutants, each containing two physically, genetically and phenotypically defined mit- lesions in cis, (that is, in the same mitochondrial chromosome). Such mutants have been constructed, and the phenotypes of several examples of each of the four possible classes--exon-exon, exon-intron (downstream), intron (upstream)-exon and intron-intron--have been examined. Our results have shown that upstream mutations are always epistatic to downstream ones for polypeptide products, and that regulation of expression of cytochrome oxidase subunit I by introns is epistatic regardless of position. These findings have provided an independent verification of the mosaic model, and also suggest that at least the majority of novel polypeptides accumulating in intron mutants are hybrid products that contain sequences of the wild-type polypeptide. PMID- 6248233 TI - Mutants of yeast initiating translation of iso-1-cytochrome c within a region spanning 37 nucleotides. AB - We used a specially constructed strain, cyc1-345, of the yeast Saccharomyces cerevisiae to isolate revertants that initiated translation of iso-1-cytochrome c at various sites along an extended region of the mRNA. Normal amounts of iso-1 cytochrome c occurred when translation initiated at the abnormal sites corresponding to amino acid positions -3, -2, 3 and 5, as well as the normal position -1; 20% of the normal amounts occurred when translation initiated at the abnormal position 9. These results with cyc1-345 revertants indicate that translation of iso-1-cytochrome c can initiate with the normal efficiency at any site within the region spanning 25 nucleotides. Furthermore, because the lower amount of the short iso-1-cytochrome c in the mutant initiating at position 9 may not necessarily reflect an inefficiency of translation, we believe that translation can initiate with normal or near-normal efficiencies at any site within a 37 nucleotide region, and presumably at any site preceding and following that of the normal initiation codon. These results establish that there is no absolute requirement for a particular sequence 5' to the initiation codon, and are consistent with our previous suggestion that translation starts at the AUG codon closest to the 5' end of the mRNA. PMID- 6248234 TI - DNA translocation by the restriction enzyme from E. coli K. AB - The restriction endonuclease Eco K binds to a host specificity site and then proceeds to cleave the DNA at sites that may to several thousand bases away. It does this by translocating the DNA past the enzyme in an ATP-dependent reaction that results in the formation of highly twisted loop intermediates. DNA cleavage can occur on either side of the host specificity site. PMID- 6248235 TI - Formation and resolution of DNA catenanes by DNA gyrase. AB - We have discovered that DNA gyrase interlocks duplex DNA circles to form catenanes and resolves catenanes into component monomers. The reactions were inhibited by novobiocin and oxolinic acid and required ATP, Mg++ and spermidine. DNA sequence homology is not involved in catenation, since hybrid catenanes were formed efficiently between supercoiled phi X174 and Col E1 DNA. Strikingly different results were obtained with native and relaxed Col E1 DNA substrates. Up to 50-60% of input native DNA was converted into oligomeric catenanes, predominantly dimers and trimers. Relaxed substrates were instead converted into vast interlocked networks and were occasionally knotted. Optimal catenation occurred only in the narrow range of 20-35 mM KCl; increased ionic strength blocked catenation completely but activated the back reaction of decatenation. Gyrase resolved both the oligomeric catenanes and interlocked networks it produced, as well as naturally occurring catenanes. These results imply that the mechanism of gyrase involves a transient double-strand break and passage of a DNA segment through the resulting gap. Gyrase is representative of a general class of enzymes, found in both procaryotic and eucaryotic cells, that facilitate diffusion of duplex DNA segments through each other and may thereby solve topological problems arising from the replication, recombination and condensation of DNA. PMID- 6248236 TI - Polarized distribution of viral envelope proteins in the plasma membrane of infected epithelial cells. AB - The surface distribution of the envelope glycoproteins of influenza, Sendai and Vesicular Stomatitis viruses was studied by immunofluorescence and immunoelectromicroscopy in infected epithelial cell monolayers, from which these viruses bud in a polarized fashion. It was found that before the onset of viral budding, the envelope proteins are exclusively localized into the same plasma membrane domains of the epithelial cells from which the virions ultimately bud: the glycoproteins of influenza and Sendai were detected at the apical surface, while the G protein of Vesicular Stomatitis virus was concentrated at the basolateral region. On the other hand, Sendai virus nucleocapsids, which can be easily identified in the cytoplasm before viral assembly, could be observed throughout the cell, not showing any preferential localization near the surface that the virions utilize for budding. These results are consistent with a model in which the asymmetric distribution of viral envelope proteins, rather than a polarized delivery of nucleocapsids, directs the polarity of viral budding. Furthermore, the asymmetric surface localization of viral glycoproteins suggests that these proteins share with intrinsic surface proteins of epithelial cells common biogenetic mechanisms and informational features or "sorting out" signals that determine their compartmentalization in the plasma membrane. PMID- 6248237 TI - Absence of nucleosomes in a fraction of SV40 chromatin between the origin of replication and the region coding for the late leader RNA. AB - Electron microscopic examination of SV40 chromatin prepared 44 hr post-infection led to the visualization of a nucleosome-free region (gap) in 15-20% of the minichromosomes. Minichromosomes with and without a gap displayed a mean number of 24 nucleosomes. Measurements carried out on dark field micrographs yielded for the gap a mean length of 249 +/- 13 bp, with a maximum value of 385 bp. The gap was mapped following digestion with three single-cut restriction endonucleases: Bgl l, Bam HI and Eco RI. It was located in the region of the origin of replication in accordance with previous biochemical data. To assess the situ existence of a nucleosome-free region, nuclei from infected cells were digested with DNase I. A highly sensitive region was thus revealed and mapped by secondary digestion with Eco RI. It was located in the same region as the gap, between 0.67 and 0.74 on the physical map. The sensitive region could be detected throughout the late phase of the virus cycle. These findings strongly suggest that a nucleosome-free region exists in the cells. The gap is not likely to be involved in replication, since it is asymmetric with respect to the Bgl I cleavage site, from which replication proceeds symmetrically. PMID- 6248238 TI - E. coli RNA polymerase interacts homologously with two different promoters. AB - We present and review experiments that identify points of close approach of the RNA polymerase to two promoters, lac UV5 and T7 A3. We identify the contacts to the phosphates along the DNA backbone, to the N7s of guanines in the major groove and the N3s of adenines in the minor groove, and to the methyl groups of thymines. These contacts to the two promoters are strikingly homologous in space, as shown on three-dimensional models, and identify major regions of interactions lying on one side of the DNA molecule (at -35 and -16), as well as further areas extending through the Pribnow box. Both promoters are unwound similarly by the polymerase, across a region of about twelve bases extending from the middle of the Pribnow box to just beyond the RNA start site. We discuss the areas of interaction in the context of promoter homologies and promoter mutations. The disposition of the contacts in space suggests a model for the pathway along which the RNA polymerase binds to promoters. PMID- 6248239 TI - Tetradecanoyl phorbol acetate stimulates latent collagenase production by cultured human endothelial cells. PMID- 6248240 TI - The initiation of SV40 DNA synthesis is not unique to the replication origin. AB - Replicative intermediates of SV40 were isolated, digested with the restriction endonuclease Bgl I and examined by electron microscopy. Over 98% of the replicative intermediates isolated following infection with wild-type virions at 33 degrees, 37 degrees or 40 degrees C or with tsA209 at 33 degrees C had initiated replication about 35 nucleotides to one side of the Bgl I site. Approximately 1% of the molecules had initiated replication about 2400 nucleotides from the Bgl I site. The remaining molecules may have initiated at other sites. When tsA209 virion-infected cultures were shifted to 40.5 degrees C for 90 min, the relative rate of thymidine incorporation into superhelical viral DNA dropped by more than 97%. The remaining incorporation was not due to "leakiness." The label incorporated into mature superhelical molecules during brief pulses was not preferentially incorporated near the terminus of replication as it was at 33 degrees C. Approximately 33% of the incorporated label represented repair synthesis. Electron microscopy revealed that half of the replicative intermediates formed under these conditions appear to have been initiated randomly around the SV40 genome. Rolling circle molecules contaminated all the preparations of replicative intermediates. PMID- 6248241 TI - Expression of polyoma early functions in mouse embryonal carcinoma cells depends on sequence rearrangements in the beginning of the late region. AB - Established mouse cell lines, primary cultures of mouse cells, and differentiated cell lines derived from mouse teratocarcinoma are permissive to polyoma virus. No viral early or late functions are expressed upon infection and penetration of multipotential embryonal cell lines. Polyoma mutants capable of growth on these cells were isolated and their DNA was cloned. Both the linear cloned viral DNA and a hybrid composed of mutant Bam HI (0.58) to Bgl I (0.72) 750 bp fragment (containing the origin of replication) ligated to the complementary wild-type 4.5 kb fragment are able to multiply on PCC4 embryonal carcinoma cells. The nucleotide sequence of two mutants indicated a genomic rearrangement on the late side of the origin, in which a deletion starting at nucleotides 46 (Py 204) and 77 (Py97) and terminating for both in nucleotide 107 was replaced by the duplication of a downstream late sequence starting at nucleotide 138 (Py 204) and 157 Py97) and terminating in nucleotide 220. The fact that the sequence rearrangements permit the expression of early and late functions upon infection suggests that this region participates in the control of early transcription. This control is different in embryonal and differentiated mouse cells. PMID- 6248242 TI - Regulatory mutants of polyoma virus defective in DNA replication and the synthesis of early proteins. PMID- 6248243 TI - Mapping of SV40 DNA replication origin region binding sites for the SV40 T antigen by protection against exonuclease III digestion. AB - Incubation of 32P-5' end-labeled DNA fragments of less than 500 bp with excess amounts of the 3' leads to 5', double strand-dependent nuclease Exonuclease III generally results in single-stranded products of slightly more than half the size of the uncleaved substrate. When such restriction fragments of known size and sequence containing the lac operator were incubated with purified lac repressor, Exonuclease III cleavage was blocked at the 3' borders of the operator on each strand. It was possible to define the DNA sequence between the two boundaries of repressor-mediated exonuclease blockade by electrophoresing the single-stranded, protected products in urea-containing polyacrylamide gels in parallel with a dimethylsulfate modification-cleavage digest of the end-labeled, uncleaved substrate. The same approach was applied to an analysis of sites of large SV40 T antigen protection in the vicinity of the origin of SV40 DNA replication. Three discrete boundaries of apparent protection were observed--one on the "late" side of the origin and two on the "early" side. These sequences may constitute the 3' borders of discrete T antigen-binding sites in the origin region. Alternatively, one or more of these blockade points may signify regions of the genome which undergo conformational changes resulting in Exonuclease III resistance due to vicinal T antigen binding. PMID- 6248245 TI - Heterogeneity of "virus-like" genes encoding retrovirus-associated 30S RNA and their organization within the mouse genome. PMID- 6248244 TI - Infectious and noninfectious recombinant clones of the provirus of SNV differ in cellular DNA and are apparently the same in viral DNA. AB - Ten clones of Charon 4A containing proviruses of spleen necrosis virus, an avian retrovirus, and flanking chicken DNA sequences were isolated and characterized. Some clones gave rise to progeny with viral DNA sequences deleted or duplicated, probably as a result of crossing-over in the 600 bp terminal redundancy in viral DNA. The cellular sequences are different in each clone, indicating that all the proviruses are integrated in different sites in cellular DNA. Six clones are infectious and four are not. All the infectious molecules containing a provirus are of a similar size and are smaller than the noninfectious molecules containing a provirus. The viral DNA is not apparently different in eight clones, but two clones, one infectious and one noninfectious, lack two restriction sites each. Large changes in proviral DNA therefore do not seem responsible for the lack of infectivity of some clones. These results are consistent with the hypothesis that neighboring cellular DNA sequences control proviral expression (infectivity). PMID- 6248246 TI - 5' terminal nucleotide sequences of type C retroviruses: features common to noncoding sequences of eucaryotic messenger RNAs. PMID- 6248247 TI - In vitro catenation and decatenation of DNA and a novel eucaryotic ATP-dependent topoisomerase. AB - Extracts from X. laevis germinal vesicles interlock duplex DNA circles to form catenanes. The catenation activity requires Mg++ and ATP. Negatively supercoiled or relaxed DNA can be used as substrates for the catenation reaction. Homology between donor and acceptor DNA is not required, since catenanes are formed between DNA molecules with unrelated sequences. In the course of the isolation of the activity responsible for the catenation reaction, we discovered a new ATP dependent topoisomerase. The fractions containing the novel topoisomerase catenate and decatenate DNA, the ionic strength dictating which of the two opposing reactions will occur. PMID- 6248248 TI - Partitioning of bacterial plasmids during cell division: a cis-acting locus that accomplishes stable plasmid inheritance. AB - We have identified and characterized a genetic function (designated par, for partition) that is required for stable maintenance of plasmids within exponentially growing cell populations. This function, which accomplishes the active distribution of plasmid DNA molecules to daughter cells, has been localized within the pSC101 plasmid to a 270 bp segment adjacent to the replication origin. The par locus, which appears to be functionally equivalent to the centromere of eucaryotic cells, is able to rescue unstable pSC101-derived replicons or an unrelated par- P15A-derived multicopy replicon in the cis, but not the trans, configuration. It is independent of copy number control and dose not specify plasmid incompatibility. Furthermore, it is not associated directly with plasmid replication functions. PMID- 6248249 TI - Improved methods for maximizing expression of a cloned gene: a bacterium that synthesizes rabbit beta-globin. AB - In this paper we describe a method for constructing E. coli plasmids that direct efficient expression of genes that encode eucaryotic or procaryotic proteins. No functional assays for the proteins are needed, and they are produced in their native, unfused state. The only requirement is that the genes be isolable without intervening sequences. We describe as an example the construction of a plasmid that directs the synthesis of about 10,000-15,000 monomers per cell of rabbit beta-globin. The essential steps in a typical construction are as follows. --A region of the gene encoding the amino-terminal portion of the protein is fused to DNA encoding an enzymatically active carboxy terminal fragment of beta galactosidase. The latter is carried on one of three plasmids designed to facilitate the fusion (the construction of these three plasmids is described in the Appendix). --A "portable promoter" of the lac operon is placed at many positions in front of the fused gene using nucleases in vitro. Those promoter placements that elicit efficient expression of the fused gene are identified by the beta-galactosidase activity that they express. (In the special case we describe, plasmids identified as directing efficient expression of beta-globin were found to bear "hybrid" ribosome binding sites consisting of the Shine Dalgarno sequence carried on the promoter fragment and the ATG of the beta-globin gene.) --The gene of interest is reconstituted intact, with the portable promoter in place, by recombination in vitro or in vivo. PMID- 6248250 TI - Cyclic GMP metabolism in macrophages. I. Regulation of cyclic GMP levels by calcium and stimulation of cyclic GMP synthesis by NO-generating agents. PMID- 6248252 TI - Influence of intracellular injection of H+ on the electrical coupling in cardiac Purkinje fibres. AB - The effect of intracellular injection of H+ on the electrical coupling of canine Purkinje cells was investigated. It was found that H+ increased the intracellular resistance (ri) and caused electrical uncoupling. The effect of high (H+)i on cell communication was partially reverted by intracellular injection of EDTA. These observations seem to indicate that the effect of low pHi on the electrical coupling can be explained, at least in part, by a rise in free [Ca2+]i. Further studies are required. PMID- 6248251 TI - The effects of 5-bromodeoxyuridine on cyclic AMP levels and cytoskeletal organization in malignant melanoma cells. AB - 5-Bromodeoxyuridine (BUdR) causes mouse melanoma cells to develop a flattened morphology and simultaneously adhere tenaceously to the substratum on which they are growing. Experiments were done to determine if these events are coupled to increases in cAMP levels and to rearrangements in the cells' cytoskeleton. Cyclic AMP assays revealed that cell flattening and the increase in adhesive properties caused by BUdR is not accompanied by an increase in the cellular concentration of cyclic AMP. However, electron micrographs of cells grown in the presence of BUdR show a striking increase in the number of organized microtubules and microfilaments. Colchicine binding revealed no difference in the amount of tubulin present in untreated or BUdR-treated cells indicating that the increase in the number of microtubules is due to the polymerization of pre-existing tubulin subunits. These results are discussed in light of possible similar mechanisms of action of BUdR and cyclic AMP in regulating the organization of microtubules and microfilaments and the role these structures play in altering cell morphology and adhesive properties. PMID- 6248253 TI - Comparison of isozymes in fetal, adult and transformed fibroblasts. AB - Differences between adult and fetal human fibroblasts have been found in the enzyme patterns of adenosine deaminase, acid phosphatase and lactate dehydrogenase. In each case the pattern seen in adult fibroblast cultures transformed with SV 40 virus resembled that of fetal fibroblasts. PMID- 6248254 TI - Effects of sulfhydryl reagents on phagocytosis and exocytosis in rabbit polymorphonuclear leukocytes. AB - The effect of sulfhydryl reagents on phagocytosis and concomitant enzyme release and on ionophore A 23187 + Ca2+-induced exocytosis in rabbit polymorphonuclear leukocytes (PMN's) was studied. Membrane-penetrating sulfhydryl reagents such as cytochalasin A and N-naphthylmaleimide in micromolar concentrations inhibit both phagocytosis and exocytosis. Poorly penetrating reagents such as p chloromercuribenzene sulfonate (pCMBS) and 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB), inhibit only in high concentrations (pCMBS), or they are ineffective as inhibitors (DTNB). Inhibition by pCMBS is not reversed by glutathione or dithiothreitol; this suggests that some pCMBS probably enters the cell. Specific intracellular sulfhydryl compounds appear to be essential in the cellular apparatus involved in phagocytosis and exocytosis; various possibilities are considered. A concentration of N-naphthylmaleimide which completely inhibits phagocytosis and exocytosis leaves cellular ATPase activity intact. PMID- 6248255 TI - The action of a mammalian endonuclease on psoralen-bound DNA. AB - The sequential actions of two enzymes believed to be involved in DNA repair, namely a mammalian endonuclease and the bacterial DNA polymerase I on psoralen bound 32P-labeled DNA, was studied. When ultraviolet-irradiated DNA is exposed to the sequential action of the endonuclease, the formation of single-strand breaks prepares the DNA for the exonucleolytic excision of thymine dimers. The mammalian endonuclease purified from rat liver to electrophoretic homogeneity is inactive on normal DNA, DNA irradiated at 360 nm or DNA mixed with psoralen without irradiation. Incubation of psoralen-bound DNA labeled with 32P with the endonuclease releases the isotope in the acid soluble indicating that psoralen bound DNA is susceptible to the endonucleolytic attack. Sedimentation of DNA on sucrose gradients indicates that there is no collapse of the DNA molecule after treatment with the endonuclease. Moreover, there is no release of the adduct in the acid soluble after treatment with DNA polymerase, indicating that the 5--3 min exonucleolytic activity of that enzyme is impaired by the remaining crosslinks. The crosslinks also inhibit the incorporation of [3H] dATP in presence of DNA polymerase I. PMID- 6248256 TI - The influence of bovine thymus hypocalcemic protein, TP1, on the levels of cyclic nucleotides in murine thymus lymphocytes. PMID- 6248257 TI - Two different forms of angiotensin I-converting enzyme from hog kidney. PMID- 6248258 TI - Influence of alkylamides of glutamic acid and related compounds on the central nervous system. IV. Effect of theanine on adenosine 3',5'-monophosphate formation in rat cerebral cortex. PMID- 6248259 TI - Synthesis of glycolipids. AB - The chemical syntheses of naturally occurring glycolipids derived from sphingosine bases and glycerol derivatives, and the syntheses of polyisoprenoid lipid intermediates and other miscellaneous glycolipids recorded up to the end of 1977 are reviewed. PMID- 6248261 TI - [Degradation of collagen by the cariogenic bacteria, Streptococcus mutans]. AB - The behaviour of cariogenic Bacteria (Streptococcus mutans) is studied with regard to collagen, which represents 90% of the dentine organic matrix. Collagenase activity of cariogenic Bacteria is measured with radioactive precursors and gel electrophoresis and compared to reference bacterial collagenase (Clostridium histolyticum). Labelled collagen substrate has been prepared with two different methods: extraction by 0,5 M acetic acid from young Rat skin, previously labelled with L-proline 14C, or reduction by Na B3H4. Both collagen sutstrates have been incubated for 2 h in Terleckyj medium in which the Streptococcus mutans have been inoculated. The experiments show a proteolytic activity of Streptococcus Mutans on the collagen substrate. PMID- 6248260 TI - [Measurement of phosphatase activity in the cell wall obtained with the help of a nonionic detergent (Triton X 100)]. AB - The phosphatase activity of cell walls isolated by treating the intact roots with Triton X 100 is very steady. It is similar to that of living roots and that of cell walls isolated by centrifugation after the grinding of the tissues. PMID- 6248262 TI - [Association of coronavirus infection with hemorrhagic entercolitis in newborn infants]. AB - The existence of a widely spread corona virus epidemic enabled us to associate this infection with necrotizing hemorrhagic enterocolitis in newborn infants. Virus is detected in the stools by direct electron microscopic examination. Virions are found agglutinated in the gut during convalescence, as they are by circulating antibodies. Arguments supporting a possible etiological role of this infection are given. PMID- 6248263 TI - [Presence of enteric viruses in non-diarrheic canine stools]. AB - Rota-, corona- and parvovirus particles have been visualized by direct electron microscopy in canine stools collected at random in Paris streets. A possible involvement of these viruses in gastroenteric diseases is discussed in the light of these findings. PMID- 6248264 TI - Naloxone reversal of hypovolemic shock in dogs. AB - The endogenous opiate ligand, beta-endorphin, is released during stress. We tested the hypothesis that endorphins may be involved in the pathophysiology of hemorrhagic shock by using the opiate receptor blocking agent, naloxone. Two groups of five anesthetized dogs were instrumented to monitor cardiovascular performance and subjected to a protocol in which they were bled into a reservoir to lower mean arterial pressure to 45 mmHg and maintained at that pressure for one hour. At that time the reservoir was clamped and on group of dogs received an intravenous bolus of naloxone (2 mg/kg) and an infusion at 2 mg/kg-hr. These dogs demonstrated a prompt increase in arterial pressure, left ventricular dp/dtmax and cardiac output. The shed blood was returned at t = 2 hr and drug infusion continued for 2 hours. The control group of dogs received saline in equivalent volume. The control dogs died within 30 minutes of clamping the reservoir while all five treated dogs survived beyond 72 hours (P less than 0.02). These data suggest the involvement of endorphins acting on opiate receptors as part of the pathophysiology in this shock model. PMID- 6248265 TI - Blockade of opiate receptors with naloxone improves survival and cardiac performance in canine endotoxic shock. PMID- 6248266 TI - Comparison of a low and high dose ACTH gel in the treatment of hay fever. AB - The present data show that in fourteen patients treated with 200 iu Acthar gel, hay fever symptoms were less during the period of peak pollen challenge during June, than those experienced by an equivalent group treated with 80 iu. Analysis of the data showed that in the seven worst sufferers in both groups the difference between treatments was statistically significant (P=0.033, estimated by analysis of covariance of the symptom scores over the period of peak pollen challenge). No serious side effects were noted in patients from either group. PMID- 6248267 TI - Carcinoma of aberrant breast tissue. PMID- 6248268 TI - Cis-Sorin corticotropin kit. PMID- 6248269 TI - Drug interferences in reactions for detecting hydrogen peroxide by means of peroxidase. PMID- 6248270 TI - The 5'-nucleotidase activity in normal human serum. Electrophoretic patterns and substrate specificity. AB - Both the electrophoretic patterns and substrate specificity of the total 5' nucleotidase activity at pH 7.4 in serum from 10 normal adults (19-49 years) were identical using various purine and pyrimidine mononucleotides as substrates. Different purified alkaline phosphatases were studied at the same time in the same manner. The serum enzymes showed substrate specificity qualitatively similar to that of the bovine liver enzyme. The electrophoretic study showed two fractions for both the liver enzyme and the serum enzymes with the different substrates, indicating that each of these are dephosphorylated by the same two, mutually different, enzyme molecules. Each of the other enzymes showed only a single fraction, which was identical for each enzyme with the various substrates. PMID- 6248271 TI - A modified method for the determination of Na-K-ATPase. AB - A modified method for determination of adenosine triphosphatase (ATPase) activities, with special reference to Na-K-ATPase, in human erythrocytes using 2 mmol/l ethylenediamine tetraacetic acid in the hemolyzing solution is presented. This modification gives stable day to day activities with a good power of discrimination. Small blood volumes and only standard laboratory equipment are needed. PMID- 6248272 TI - Primary hyperparathyroidism with intermittent hypercalcaemia: serial observations and simple diagnosis by means of an oral calcium tolerance test. AB - Ten patients with subtle primary hyperparathyroidism and intermittent hypercalcaemia were followed serially for periods of 2--18 months (mean 10 months). Fasting serum calcium was elevated (greater than 10.6 mg/dl) in only 20% of determinations and fluctuated widely (9.1--11.2 mg/dl), yet the patients displayed a continuous, rather than episodic, basic disease process as defined by increases in nephrogenous cyclic AMP and serum iPTH. Identical findings were noted in short-term (2--3 successive days) studies in twelve patients. In response to a 1000 mg oral calcium tolerance test, twelve patients with primary hyperparathyroidism and intermittent hypercalcaemia (basal serum calcium 10.2 +/- 0.2 mg/dl, mean +/- SD) displayed: (1) hyperabsorption of calcium (mean calciuric response twice normal); (2) induced-hypercalcaemia (mean serum calcium 11.4 mg/dl, with a mean increase of 1.2 mg/dl versus 0.2 mg/cl in normal subjects); and (3) abnormal parathyroid suppressibility (nephrogenous cyclic AMP 2.66 +/- 0.57 nmol/100 ml GF versus 0.95 +/- 0.40 nmol/100 ml GF in normal subjects, mean +/- SD). The patients demonstrated striking hypercalciuria (452 +/- 123 mg/24 h) on a 1000 mg metabolic calcium diet. Serum levels of 1,25(OH)2D3, measured in ten patients, were markedly elevated at 90 +/- 20 pg/ml (mean +/- SD), and there was a strong positive correlation between the values for 1,25(OH)2D3 and the calciuric response to the calcium tolerance test (r = 0.75, P less than 0.001). These results (1) indicate that the calcium tolerance test is a simple and reliable technique for diagnosis of patients with primary hyperparathyroidism and intermittent hypercalcaemia, and (2) emphasize the important pathophysiologic features of this subtle clinical variant of primary hyperparathyroidism. PMID- 6248273 TI - Aldosterone regulation in primary aldosteronism: influence of salt balance, posture and ACTH. AB - The response of aldosterone to manipulations of the renin-angiotensin and hypothalamic-pituitary-adrenal systems has been studied in thirteen patients with primary aldosteronism due to a single adenoma (ten patients) or bilateral hyperplasia (three patients). The aldosterone response to dietary sodium restriction was small and variable, although urinary aldosterone excretion increased in nine out of twelve studies. The response of patients with hyperplasia could not be distinguished from those with adenoma. All patients were unresponsive to salt loading. By contrast, plasma aldosterone fell in all patients after overnight dexamethasone (1 mg) and increased after brief (1 h) physiological ACTH stimulation. During prolonged erect posture, plasma aldosterone increased in the three patients with hyperplasia and decreased or remained unchanged in patients with ademona. Changes in plasma renin activity were similar in both groups. These studies show that patients with primary aldosteronism, while largely unresponsive to manipulations of sodium balance, retain sensitivity to small and acute changes in ACTH. The different behaviour of patients with hyperplasia to prolonged erect posture cannot be explained by insensitivity to ACTH, but could be due to a relative increase in sensitivity to angiotensin. PMID- 6248274 TI - beta-Endorphin and beta-MSH in human plasma. AB - The aim of this study was to establish whether or not a peptide with chromatographic and immunological properties of beta-endorphin exists in human plasma. Using direct chromatography under conditions designed to minimize generation of beta-endorphin and beta-MSH from beta-LPH, we invariably found a peptide with beta-endorphin immunoreactivity eluting in the position of beta h endorphin on gel chromatography in samples of plasma from patients with elevated ACTH and LPH levels. beta-MSH was only found in the plasma of one patient with the ectopic ACTH syndrome. PMID- 6248275 TI - [Effect of angiotensin converting enzyme inhibitor (SQ 14225) on renin-angiotesin sytem and haemodynamics (author's transl)]. PMID- 6248276 TI - [Influence of glucocorticoids on TSH secretion in man (author's transl)]. PMID- 6248277 TI - A case of Mulibrey nanism with associated Wilms' tumor. AB - The occurrence of a nephroblastoma in a 2-year-old girl with Mulibrey nanism is reported. As this tumor has also been reported in some other "mesodermal dysgenesis" syndromes, it seems probable that patients with this form of congenital disease run an abnormally high risk of Wilms' tumor. PMID- 6248278 TI - Adjuvants in the induction and enhancement of rat IgE responses. AB - In Hooded Lister rats the primary IgE antibody response induced by immunization with antigen and adjuvant may be enhanced either specifically by a further dose of antigen (booster response) or non-specifically by infection with helminth parasites (potentiated response). The initial immunizing technique can influence the occurrence and level of these enhanced responses and here we describe the effect of using different adjuvants in the priming event. Although the level of the primary response was broadly similar following immunization with egg-albumin and the adjuvants Bordetella pertussis aluminium hydroxide or Freund's complete adjuvant, the booster response was inhibited and the potentiated response intensified in animals immunized with the latter two adjuvants. A significant IgE booster response could only be obtained if B. pertussis had been used in the initial immunization. When aluminium hydroxide was adsorbed to B. pertussis it was found to have the same inhibitory effect on subsequent booster responses as when it was adsorbed to antigen. These results are discussed in relation to the intricacies of IgE production in the present model and to more general mechanisms of adjuvant action. PMID- 6248279 TI - Acute cytomegalovirus infection and the host immune response. I. Development and maintenance of cytomegalovirus (CMV) induced in vitro lymphocyte reactivity and its relationship to the production of CMV antibodies. PMID- 6248280 TI - Acute cytomegalovirus infection and the host immune response. II. Relationship of suppressed in vitro lymphocyte reactivity to bacterial recall antigens and mitogens with the development of cytomegalovirus-induced lymphocyte reactivity. PMID- 6248281 TI - Lymphocyte 5'-nucleotidase in primary hypogammaglobulinaemia and cord blood. AB - The 5'-nucleotidase (5'-N) deficiency on circulating mononuclear cells of patients with 'common variable' hypogammaglobulinaemia (CV-H) was shown to be the result of one or more of three factors: reduced T cell 5'-N activity, a reduced percentage of circulating B cells, and a low B cell 5'-N activity. A lack of circulating B lymphocytes, together with a low T cell 5'-N activity in some cases, was found to be responsible for the deficiency of lymphocyte 5'-N in patients with X-linked hypogammaglobulinaemia (X-H). The low levels of 5'-N activity in CV-H and X-H patients were not due to abnormal compartmentalization of the enzyme, altered enzyme kinetics, or the presence of a regulatory factor. Cord Blood B and T cells have a lower 5'-N activity than adult lymphocytes. The patient and cord blood data are discussed in relation to the stage of cellular maturity. PMID- 6248282 TI - The comparative selectivity of adjuvants for humoral and cell-mediated immunity. I. Effect on the antibody response to bovine serum albumin and sheep red blood cells of Freund's incomplete and complete adjuvants, alhydrogel, Corynebacterium parvum, Bordetella pertussis, muramyl dipeptide and saponin. AB - A comparison was made of seven recognized adjuvants, Freund's incomplete and complete, alhydrogel, Corynebacterium parvum, Bordetella pertussis, muramyl dipeptide and saponin, administered with BSA or SRBC by the S.C. route of immunization. Strong selectivity as well as differences in potency were revealed in relation to these two antigens. Only FIA, FCA, alhydrogel and MDP promoted the primary response to 50 microgram of BSA, and FIA was significantly superior to FCA. Immunological memory to a low dose (0.5 microgram) of BSA, which did not evoke a primary response with any adjuvant, was potentiated by alhydrogel and by MDP and, relatively poorly, by FIA. Radioimmunoelectrophoresis showed that potentiation of the response with MDP was confined to IgG1, whereas alhydrogel, FIA and FCA stimulated both IgG1 and IgG2. Saponin was outstandingly the best adjuvant for both primary and secondary haemagglutinin responses to SRBC. Of the others, alhydrogel for the primary, and alhydrogel and B. pertussis for the secondary were active to a lesser degree. The results show that the relative potency of adjuvants differs markedly according to the antigen used, and suggest that saponin may be a particularly effective adjuvant for antigens in cell membranes. PMID- 6248283 TI - The comparative selectivity of adjuvants for humoral and cell-mediated immunity. II. Effect on delayed-type hypersensitivity in the mouse and guinea pig, and cell mediated immunity to tumour antigens in the mouse of Freund's incomplete and complete adjuvants, alhydrogel, Corynebacterium parvum, Bordetella pertussis, muramyl dipeptide and saponin. AB - Corynebacterium parvum was the only adjuvant of those tested which consistently potentiated delayed-type hypersensitivity (DTH) to sheep red blood cells (SRBC) in the mouse, although this required the antigen-adjuvant mixture to be injected subcutaneously in the footpad rather than the flank. For induction of DTH to ovalbumin (OVA) in the guinea pig, C. parvum and MDP could be substituted for the mycobacteria in FCA. C. parvum was effective in aqueous solution provided that the OVA was absorbed onto alhydrogel. Saponin also potentiated DTH when injected with OVA in aqueous solution. C. parvum was the sole adjuvant of those tested to promote protective cell-mediated immunity (CMI) to M4 fibrosarcoma cells. It is concluded that C. parvum is a promising candidate adjuvant for promoting CMI induction without recourse to a water-in-oil emulsion. PMID- 6248284 TI - Production of antibodies to host IgG after transfer of histocompatible cells primed to host allotype. AB - A method is described to bring about endogenous production of antibodies to the Fc region of IgG. Mice of one allotype (Igb) were immunized against immunoglobulin from a congenic strain of mice bearing another allotype (Iga). The Iga-primed cells were transferred to congenic recipients bearing the Iga allotype and the production of anti-host allotype antibodies by the donor cells measured. Low levels of anti-host allotype antibodies were found in the sera of normal recipients but much greater amounts in recipients pretreated with cyclophosphamide. On ultracentrifugation some of these IgG antibodies sedimented at more than 7S probably because they were complexed with the IgG antigen. It is considered that thismodel may be of use in testing the effect of anti-Fc antibodies on joint inflammation. PMID- 6248285 TI - Role of hydrogen peroxide in the cytotoxic reaction of T lymphocytes. AB - Evidence is presented that T lymphocyte cytotoxicity is mediated by hydrogen peroxide (H2O2). At a concentration of 5 x 10(-4) M H2O2 induced 51Cr release from pre-labelled P815 mastocytoma cells. H2O2 was generated when T lymphocytes from mouse spleen were exposed to P815 cells. The concentration of H2O produced was apparently one thousand times lower than the concentration required to lyse the P815 cells. This suggests that the H2O2 is produced and acts at a highly localized site on the target cell. Sulphydryl groups on the target cell were particularly sensitive both to H2O2 and to spleen cell attack. The activity of the spleen cells was inhibited by cyanide and azide and by reducing agents which protected the target cells. Cytotoxicity was enhanced by agents which prevented H2O2 breakdown. PMID- 6248286 TI - Tc-99m-pyrophosphate bone scan in calcinosis universalis. PMID- 6248287 TI - Increased renal accumulation of Tc-99m-MDP in renal artery stenosis. AB - Abnormal increased renal accumulation of Tc-99m-MDP was observed in a patient found subsequently to have stenosis of the ipsilateral renal artery. The case is both interesting in itself and for its possible implications regarding the use of radiolabeled phosphates in renal ischemia. PMID- 6248288 TI - Position-related false-positive renal imaging. AB - A case report of false-positive renal imaging due to anterior displacement of the upper pole of the left kidney with the patient in the prone position is presented. False imaging can be avoided by imaging the kidneys with the patient in the supine position and with the detector behind the patient. PMID- 6248289 TI - A radioreceptor assay for propranolol and 4-hydroxypropranolol. AB - A radioreceptor assay for the measurement of propranolol and 4-hydroxypropranolol levels in plasma is described. Maximum sensitivity for propranolol was 1.2 +/- 0.15 ng/ml and for 4-hydroxypropranolol 4.2 +/- 0.4 ng/ml. Interassay and intra assay variations for both were under 10%. Modifications in the radioreceptor assay permitted the measurements of total beta-adrenergic blocking activity and the separate contributions of parent drug and metabolite. When 4 hydroxypropranolol was stabilized, a composite level of total beta-adrenergic blocking activity in plasma was obtained. When the 4-hydroxy metabolite was oxidized, only the stable parent drug was detected. The difference in values between measurements made under these conditions was equivalent to the amount of 4-hydroxypropranolol in the sample. The radioreceptor assay was also used to measure the amount of free propranolol and 4-hydroxypropranolol. Under identical experimental conditions, more 4-hydroxypropranolol than propranolol circulated in the free form. These observations establish the feasibility of adapting the radioreceptor assay for propranolol to the measurement of total beta-adrenergic blocking activity and its components in plasma as well as to the measurement of free drug and metabolite levels. PMID- 6248290 TI - [Changes in pituitary activity in patients with cranioencephalic injuries]. PMID- 6248291 TI - Analysis of a study of menses induction using a vaginal suppository containing 3.0 mg 15(S)-15-methyl-PGF2 alpha methyl ester. PMID- 6248292 TI - Transfer factor. AB - The understanding of passive transfer of cell mediated-immune responses with transfer factor and other cell free materials has progressed to the point that investigators are seeking the chemical identity of the molecule(s) that are responsible for these effects and are working on their mechanisms of action. In addition, clinical trials are underway that should clarify the potential for use of transfer factor in treatment of infections, neoplastic and autoimmune diseases. This chapter will critically review the past and current data concerning the components of transfer factor and their effects on immunologic and inflammatory reactions. Some of the recently developed animal models will be described and evaluated, and the clinical studies that have provided conclusive data regarding efficacy will be reviewed. PMID- 6248293 TI - The effect of pentoxifylline on red cell deformability in cerebrovascular accidents. AB - A study was carried out in 49 recent cerebrovascular accident (CVA) patients to compare red cell deformability in this group with that in 65 healthy controls. Deformability was determined using a standard technique for measuring blood filtration time through a micropore filter. Filtration time was shown to be significantly reduced in the CVA patients. All patients had ACTH treatment, 28 of them receiving in addition 600 mg pentoxifylline per day, either by intravenous infusion or by intramuscular injection. After 2-weeks' treatment, red cell deformability was increased in the patients treated with pentoxifylline and ACTH and was unchanged in the 21 patients receiving only ACTH (p less than 0.001). The authors discuss the role of increased red cell deformability in the clinical prognosis of the patients. PMID- 6248294 TI - Cutaneous herpes simplex infections and their treatment. AB - Herpes simplex virus causes many important systemic as well as cutaneous diseases. The most common cutaneous diseases are herpes gingivostomatitis, labialis, and genitalis. Many new treatments for these diseases are proclaimed each year. There are so many treatments that one would believe that either everything works or nothing works. As there is no Federal Drug Administration approved treatment for cutaneous herpes simplex, the latter statement is probably more correct. Regardless of this dilemma, the physician must continue to diagnose and treat many cutaneous herpetic infections. In this paper the basic concepts of the herpes simplex virus will be briefly presented. Additionally, the most common cutaneous herpes infections will be reviewed with emphasis on critical analysis of their proposed methods of treatment. PMID- 6248295 TI - Inhibition of mitochondrial-specific protein symthesis in human lymphocytes and platelets is dependent upon the stage of cellular differentiation. AB - Small lymphocytes differentiate into functionally active blast cells in vitro upon stimulation with such mitogens as phytohemagglutinin and sodium periodate. If stimulated lymphocytes are subsequently treated with the nucleic acid intercalating dye ethidium bromide, electron-dense complexes containing nucleic acid are formed in mitochondria, protein synthesis in mitochondria is inhibited, and lymphoblast division ceases. Formation of complexes and the development of morphologically abnormal mitochondria provide ultrastructural evidence of mitochondrial protein inhibition and serve as markers for mitogen-responsive lymphocytes. The formation of these abnormalities in all mitochondria of treated megakaryocytes and 22% of mitochondria in platelets indicates that platelets contain functional nucleic acid and that the induced structural changes may be occurring in a less-differentiated (i.e., younger) subpopulation of circulating platelets. PMID- 6248296 TI - A characterization of mitochondrial and mycoplasmal DNAs associated with cloned HeLa thymidine kinase minus cells. AB - HeLa S3 cells were cloned, recloned, and then selected for growth in the presence of increasing concentrations of bromodeoxyuridine. Cultures of these cloned thymidine kinase minus (TK-) cells were found to harbor mycoplasma which sedimented with mitochondria in sucrose density step gradients. Examination of mitochondrial DNA (mitDNA) components by restriction enzyme analysis and electron microscopy revealed no gross alterations in size, sequence arrangements, or replicative forms compared with mitDNA of HeLa S3 cells. Restriction enzyme cleavage sites for BamHI (one site), PstI (two sites) and HpaI (three sites) were mapped on this genome relative to the three cleavage sites for each of EcoRI and HindIII, respectively. Analysis of topological complexity revealed similar frequencies of catenated mitDNA molecules in both cloned TK- (22.5 +/- 1.5% of mass) and HeLa S3 cells )25.6 +/- 1.5% of mass). Unicircular dimers comprise 6.7 +/- 0.9% of the mitDNA mass in cloned TK- cells but were not detected in HeLa S3 mitDNA. Examination of the mycoplasmal contaminant of mitochondrial DNA after digestion with various restriction enzymes and agarose gel electrophoresis revealed that most of the DNA was distributed in discretely sized fragments in patterns that can probably be used to unambiguously identify and classify the organism. PMID- 6248297 TI - Integration site(s) of herpes simplex virus type 1 thymidine kinase gene and regional assignment of the gene for aminoacylase-1 in human chromosomes. AB - To investigate the chromosomal sites of integration of the herpes simplex virus type 1 (HSV-1) thymidine kinase (TK) gene in HSV-1-transformed human HeLa(BU25)/KOS 8-1 cells, the biochemically transformed cells were fused with TK negative mouse LM(TK-) cells, and human-mouse somatic cell hybrid lines (LH81) were isolated using a HATG-ouabain selection system. The presence of HSV-1 TK activity in the hybrid lines was verified by disc polyacrylamide gel electrophoresis (PAGE) and by enzyme neutralization with type-specific rabbit anti-HSV-1 TK immunoglobulin. Karyotype analyses of several somatic cell hybrid clones using G-banding, Hoechst 33258 staining, and combined G-banding and Hoechst staining demonstrated that they retained only a few human chromosomes. A marker chromosome, M7, consisting of a chromosome 17 translocated to the short arm of 3, occurred in 25 of the 28 metaphases examined. Also chromosomes 8 and X were found in a minority of metaphases. Isozyme analyses showed that all 19 hybrid clones analyzed expressed human aminoacylase-1 (ACY1) and esterase D (ESD), markers for 3 and 13, respectively. Back-selection of somatic cell hybrid clones with 5-bromodeoxyuridine resulted in the isolation of several subclones lacking HSV-1 TK activity, human ACY1, human ESD, and the human chromosomes. These experiments suggest that the HSV-1 TK gene is associated with either M7 or a segment of 13, or both, in biochemically transformed HeLa(BU25)/KOS 8-1 cells. These experiments also permit localization of the ACY1 structural gene to the pter leads to p12 region of 3. PMID- 6248298 TI - Regional chromosome mapping of the human skin type I procollagen gene using adenovirus 12-fragmentation of human-mouse somatic cell hybrids. AB - Prevous work, using human-mouse somatic cell hybrids, has localized the structural gene for human skin type I procollagen (COL 1) to chromosome 17. One of these hybrids contained only the long arm of human chromosome 17, translocated onto a mouse chromosome, as human chromosomal material. This hybrid was treated with adenovirus 12, and various clones were picked which contained different sized fragments of human chromosome 17 that were still translocated onto a mouse chromosome. Measurements of these fragments, combined with assays for human COL 1 production and galactose kinase (GAK) activity (also localized on the long arm of human chromosome 17), has allowed us to regionally map the structural gene for human COL 1 to an area just distal to the thymidine kinase (TK) and GAK genes within bands q21 and q22 on human chromosome 17. PMID- 6248299 TI - Antitrypanosomal activity of trivalent antimonials in vitro and its significance. AB - The SbIII preparations available for clinical use were compared in vitro for their concentration/time/effect curves on Trypanosoma venezuelense (T. evansi), measuring decrease of motility and of parasite numbers. With these two criteria leading to similar relative results, the drugs are classified into a rapidly acting group, led by sodium emetic (AST), followed by its dimethylcysteine chelate (NAP) and Anthiomaline, and a less and more slowly acting one: Triostam, Astiban and Stibophen. The relative activity of these drugs in vitro is parallel to that encountered against Schistosoma mansoni, attributed to a similar pattern of intracellular absorption. In vivo effectiveness may depend on bioavailability of Sb in the host and the direct action on the parasite, reflected by its in vitro activity. The interplay of these two factors leads to a different in vitro/in vivo activity relationship of the antimonials even in the same host (mouse) and to its variation in other host species. PMID- 6248300 TI - In vitro evaluation of new penicillins and cephalosporins upon P. aeruginosa and their interaction with mecillinam. AB - The in vitro activity of the new semisynthetic ureidopenicillins azlocillin (AZ) and mezlocillin (MZ), and of the new cephalosporin cefsulodin (CEF) were determined against 50 carbenicillin-sensitive (CARs) and 50 carbenicillin resistant (CARr) P. aeruginosa clinical isolates. In the CARs group the most active antibiotics are AZ and CEF with MICs between 0.5 and 8 microgram/ml. Ticarcillin (TIC) and MZ showed more activity than CAR with MICs from 2 to 32 mu/ml. In this group there is a predominance of pyocine-type groups 1 and 3. In the CARr group, AZ is the most active antibiotic at low concentrations. At 64 microgram/ml of CEF, 72% of strains are inhibited as compared to 70% with AZ, 62% with MZ and 50% with TIC. In this group there is predominance of non-typeable strains. Interaction with mecillinam (MEC) and these antibiotics was studied on three different culture media (MH, NIH and DST). There were few cases of synergism with MEC and TIC combinations, mostly on DST medium. No appreciable synergism was found with other combinations of antibiotics. PMID- 6248301 TI - Antibacterial activity of HR-756, cefoxitin and cefuroxine against multiply antibiotic-resistant strains of Enterobacteriaceae and Pseudomonas aeruginosa. AB - The in vitro antibacterial activity of HR-756 compared to cefoxitin and cefuroxime. 122 multiresistant clinical isolates including Enterobacteriaceae (104) and P. aeruginosa (18), which present particular problems in antibiotic chemotherapy, were selected for study. HR-756 inhibited all the stains of S. marcescens, P. mirabilis and indole-positive Proteus spp. at a concentration of 1,3 and 12 micrograms/ml, respectively; beta-lactamase-producing strains were also susceptible. 90% of K. pneumoniae and more than half of the Enterobacter and P. aeruginosa were inhibited from the drug at a concentration 16 microgram/ml. Cefoxitin and cefuroxime were less active than HR-756. Cefoxitin was more effective against S. marcescens and P. mirabilis while the same was the case with cefuroxime against K. pneumoniae strains. The greater efficiency of HR-756 over cefoxitin and cefuroxime against these multiply resistant isolates seems to be due not only to its indifference to the beta-lactamases but also to its easier penetrability into the bacterial cell. PMID- 6248302 TI - [Enhanced enzymatic activity of Crohn's disease and ulcerative colitis (author's transl)]. AB - 1. An enhanced collagenolytic activity in the bowel tissue samples of M. Crohn and ulcerative colitis is demonstrated. 2. No inhibition of the collagenolytic activity was found when the specific collagenase inhibitor EDTA was applied. 2. In vitro, the application of EGLIN B resulted in a significant decrease of collagenolysis. EGLIN is a recently detected inhibitor of serine proteases such as Elastase. PMID- 6248303 TI - [Progress in the localization of insulinomas]. AB - Preoperative percutaneous transhepatic portal vein catheterization with selective blood sampling from the pancreatic veins and insulin radioimmunoassay is a very successful new procedure for localization of insulinomas. A careful peroperative inspection and bidigital palpation of the whole pancreas helps to avoid the problems of undetected insulinoma. PMID- 6248304 TI - [Controlled experimental histological and microbiological studies on the inhibitory effect of polyglycolic acid sutures in infections]. AB - In the first experimental series, 3-0 PGS sutures which had been contaminated with staphylococcus aureus were situated in rat muscle in vivo. After periods of 20, 30, 40, 50, and 60 days, these sutures were removed and investigated histologically. After 20 days, the tissue surrounding the suture surface was much inflamed, showing inflammation cells and bacteriae, whereas after 60 days no signs of inflammation were to be seen. By hydrolysis of the PGS thread to the monomere glycolic acid, a bacteriostatic and bactericidal milieu seems to develop. In the second experimental series, purely in vitro, the fungicidal and bactericidal properties of glycolic acid were proved microbiologically. Furthermore, in two investigations PGS did not show fungicidal or bactericidal properties. When using PGS sutures, inhibition of the growth of fungi and bacteriae is based on the hydrolysis of PGS to glycolic acid. PMID- 6248305 TI - [Surgery for organo-pancreatic hypoglycemia. 36 cases (author's transl)]. PMID- 6248306 TI - [Poland syndrome (author's transl)]. PMID- 6248307 TI - Isolation and mapping of the rRNA genes in the macronucleus of Oxytricha fallax. AB - The DNA in the macronucleus of the protozoan Oxytricha, unlike like that of typical eukaryotes, exists as short, gene-sized molecules. Within the macronucleus the rRNA genes are contained in molecules 7,380 nucleotide pairs in length. This rDNA has been substantially purified by selective denaturation of non-ribosomal DNA followed by S1 nuclease digestion. Results from restriction nuclease digestion and rRNA:DNA hybridization who that the rDNA is a linear, non palindromic molecule which contains one gene each for the 19s and 25s rRNAs. A total of less than 600 base pairs of DNA lies between the 19s and 25s genes or at the 3' end of the 25s gene. The non-coding portion of the ribosomal DNA is almost entirely limited to an approximately 1,400 base pair region at the 5' end of the molecule. PMID- 6248308 TI - Arrangement of coding and non-coding sequences in the DNA molecules coding for rRNAs in Oxytricha sp. DNA of ciliated protozoa. VII. AB - All of the genes in the macronucleus of Oxytricha sp. occur on physically separate "gene-sized" DNA molecules. We have inserted the DNA molecule that codes for rRNA into a bacterial plasmid in order to study its structure and function. Using restriction nuclease mapping and hybridization of 125I-rRNAs to gel separated DNA fragments we have determined that the intact rDNA is 8,140+/-50 base pairs (bp) in length. Reading from one end, the molecule consists of approximately 1,540 bp of non-coding DNA, approximately 2,100+/-50 bp that code for 19S rRNA, approximately 3,700+/-50 bp that code for 25 rTNA, and approximately 620+/-50 bp of non-coding DNDA. The 5.8S rRNA coding sequence (approximately 150 bp) occurs at one end of the 25S RNA coding region but which end is not known yet. All three rRNAs are encoded in the same strand of the DNA molecule, and transcription is in the order: 19S leads to 25S. PMID- 6248309 TI - Management of inflammatory bowel disease: an effective and concise approach. AB - Experience in treating 100 patients with inflammatory bowel disease, for periods ranging from one to 15 years, is reviewed. A concise clinical classification of inflammatory bowel disease, correlated with a method of management, is presented. Relative rates of operation appear to be reduced over previously reported series: among chronic ulcerative colitis patients, 11 per cent had major precedures; for Crohn's disease, 36 per cent. PMID- 6248310 TI - Classic articles in colonic and rectal surgery: Sir James Paget, 1814-1899, on disease of the mammary areola preceeding cancer of the mammary gland. PMID- 6248311 TI - Influence of dietary fiber on transit time, fecal composition, and myoelectrical activity of the primate right colon. AB - The effect of varying dietary fiber intake on colon motor and electrical spike activity, transit time, and fecal content were studied in stump-tailed monkeys. Mean dry fecal weight increased with increasing fiber intake, but percentage water content did not change. Mean transit time was delayed when the diet contained less than 10 g dietary fiber daily. The clearance of polyethylene glycol and chromium sesquioxide also was slower on a low-fiber intake. Electrical spike discharge activity was greatest in the cecum and increased with increasing fiber intake. The effect of fiber on electrical spike activity progressively decreased distally along the colon. The contraction frequency of circular muscle, recorded with implanted strain gages, was greater in the cecum on a low-fiber diet, but this effect was less marked in transverse colon, and no significant differences were seen more distally. PMID- 6248312 TI - [New F-like genetic transfer factor pAP38 and its compatibility with F-group incompatibility plasmids]. PMID- 6248313 TI - [Map of Eco RI, Bam HI, Sal I, Hind III, Pst I, Xba I restriction endonuclease cleavage of Misgurnus fossilis loach mitochondrial DNA]. PMID- 6248314 TI - When drugs can help in multiple sclerosis. PMID- 6248315 TI - Effect of alkyl chain on the uptake, distribution, and excretion of 35S-labeled alkyl sulfates in carp. PMID- 6248316 TI - [Opiate receptors and endogenous morphinelike peptides in the brain]. AB - In the review the authors describe the basic achievements in the given field: the discovery of receptors of opiates, localized on the cellular membrane of the neurone; investigation of their topographic distribution at various zones of the central nervous system: the discovery of endogenous ligands for opiate receptors enkephalins and endorphins; distinction of two systems of opiate receptors in the central nervous system--enkephalinic and beta-endorphinic; a study on the relationships between endogenous morphines and other neuropeptides and neurotransmiters and neuromodulators; investigations on the connections between endorphins and cyclic nucleotides. The authors discuss briefly the proposed hypothesis about the function of the opiate receptors and endogenous morphines in normal and pathologic states. PMID- 6248317 TI - [Effect of thiol compounds on aniline toxicity and aniline metabolism]. AB - The authors examined systematically the influence of some thiol compounds on the drug metabolism, investigating the effect of potassium ethylxanthogenate, diethyldithiocarbamata, inithiol and penicilamine on the aniline toxicity, methemoglobin formation and aniline-hydroxylase activity. They found that the examined compounds increased aniline toxicity in white male rats. These compounds inhibited aniline-hydroxilase activity. The connection between the increase of the toxicity of aniline under the influence of the examined compounds and their inhibiting action on the metabolism of aniline was discussed. PMID- 6248319 TI - The effects of ions, metabolic inhibitors, and colchicine on luteinizing hormone releasing hormone release from superfused rat hypothalami. PMID- 6248318 TI - Changes of blood levels of several hormones, catecholamines, prostaglandins, electrolytes and cAMP in man during emotional stress. AB - The levels of several hormones (ACTH, GH, TSH, FSH, LH, parathyroid hormone--PTH, insulin, thyroxine--T4, triiodothyronine--T3, cortisol, testosterone, aldosterone, renin), catecholamines (epinephrine, norepinephrine, dopamin), prostaglandins (F1 alpha, F2 alpha, A + E), electrolytes (Na, K, Ca, Mg), cAMP and glucose in blood were measured before and immediately after the examination in 15 male students aged 28 to 35 years. Simultaneously the blood pressure was measured and hemodynamic measures were registered with the aid of echocardiography. A remarkable increase of catecholamines, ACTH, renin, T3, PTH, cAMP, PG F1 alpha, PG F2 alpha and Ca was found before the examination together with the increase of blood pressure. After the examination the levels of catecholamines, renin, aldosterone, T3, PTH, GH, FSH, LH, testosterone, PG A + E, glucose and Ca were found to be increased, while these of insulin, Na, PG F1 alpha, PG F2 alpha were decreased. The decrease of blood pressure was also found. PMID- 6248320 TI - Ovarian gonadotropin-releasing hormone receptors. I. Properties and inhibition of luteal cell function. PMID- 6248321 TI - Ovarian gonadotropin-releasing hormone receptors. II. Regulation and effects on ovarian development. PMID- 6248322 TI - Effect of in vivo treatment with adrenocorticotropin and hypophysectomy on adrenal adenosine 3',5'-monophosphate and corticosterone responsiveness to adrenocorticotropin stimulation in vitro. PMID- 6248323 TI - Beta-endorphin and adrenocorticotropin in extrapituitary sites: gastrointestinal tract. AB - Beta-Endorphin and ACTH immunoassays were employed to examine the concentrations, distributions, and character of those peptides in rat gastrointestinal tissues. Sections of the gastrointestinal tract were obtained from fasted and fed animals and were extracted in 5 N acetic acid containing proteolytic enzyme inhibitors. Aliquots immunoassayed for beta-enddorphin and ACTH revealed highest concentrations to be present in the small bowel, with stomach and colon containing little immunoreactivity. Tissues from fasted animals contained more immunoreactivity than did those from fed animals. Gel chromatography showed the presence of large molecular weight forms of beta-endorphin and ACTH in gut extracts. Concanavalin A affinity chromatography revealed that approximately 5% of gut immunoreactivity contained carbohydrate. Therefore, beta-enddorphin and ACTH immunoreactivities are present im the gut. The demonstration of large molecular weight and glycosylated forms of immunoreactivity suggests the presence of biosynthetic precursors of beta-endorphin and ACTH. The increase in immunoreactivity in response to fasting suggests that these peptides play a role in gut physiology. PMID- 6248324 TI - The lack of relationship between luteinizing hormone receptors in the rat corpus luteum and the critical need for luteinizing hormone in the luteotropic process. PMID- 6248325 TI - Luteinizing hormone-releasing hormone-induced delay of parturition. PMID- 6248326 TI - Establishment of a calcitonin-producing rat medullary thyroid carcinoma cell line. I. Morphological studies of the tumor and cells in culture. PMID- 6248327 TI - Identification of a receptor-binding region in parathyroid hormone. PMID- 6248328 TI - The imprinting of adult hepatic monoamine oxidase levels and androgen responsiveness by neonatal androgen. PMID- 6248329 TI - Temporal alterations in luteinizing hormone-releasing hormone concentrations in several discrete brain regions: effects of estrogen-progesterone and norepinephrine synthesis inhibition. PMID- 6248330 TI - Specific binding of growth hormone by rat adipocytes. PMID- 6248331 TI - Effects of adrenocorticotropin on pregnancy and prolactin in mice. PMID- 6248332 TI - Effects of cyclic nucleotides on deoxyribonucleic acid synthesis in hypophysectomized rat cartilage: stimulation of thymidine incorporation and potentiation of the action of somatomedin by analogs of adenosine 3',5' monophosphate or a cyclic nucleotide phosphodiesterase inhibitor. AB - The actions of cyclic nucleotides on basal and somatomedin-stimulated thymidine incorporation into DNA by costal cartilage from hypophysectomized rats were investigated. Three analogs of cAMP (dibutyryl, 8-bromo, and 8-dimethylamino derivatives, which are alternate activators of cAMP-dependent protein kinase and resistant to degradation by cAMP phosphodiesterase but represent a wide difference in potency as phosphodiesterase inhibitors) in range of concentrations from about 10(-5) to 3 X 10(-4) M enhanced basal and somatomedin-stimulated thymidine incorporation. Each cAMP analog at optimal concentration produced combined effects with a suboptimal concentration of somatomedin which were additive or greater. cAMP itself, 5'-AMP, adenosine, 8-Br-5'-AMP, 8-Br-AMPT, and cGMP at concentrations from 10(-7)--10(-3) M or dibutyryl cGMP at concentrations from 10(-10)--10(-3) M did not reproduce the effects of the cAMP analogs. A phosphodiesterase inhibitor (1-methyl-3-isobutylxanthine) at concentrations of 100 or 500 microM also potentiated the effects of somatomedin. At 100- or 500 microM concentrations, the phosphodiesterase inhibitor increased cartilage levels of cAMP and cGMP. These results suggest a role for cAMP in DNA synthesis in rat cartilage. However, they fail to support the hypothesis that all effects of somatomedin on that process are mediated by cAMP, since stimulation of thymidine incorporation by the hormone can be demonstrated in cartilage maximally stimulated by analogs of cAMP. PMID- 6248333 TI - A further study of 17 beta-hydroxysteroid oxidoreductase in the human testis: mechanism of in vitro activation. AB - The mechanism and specificity of product activation of 17 beta-hydroxysteroid oxidoreductase for interconversion of androstenedione and testosterone were investigated using cell-free homogenates of human testes as an enzyme preparation. The reactions of oxidation and reduction catalyzed by the enzyme followed the Michaelis-Menten formula Addition of testosterone to the incubation medium resulted in increased Vmax and decreased the Km of reductase function of the enzyme. Androstenedione added to the incubation medium increased both Vmax and Km of the enzyme for the oxidase function. The apparent Km of the reductase function for [3H] androstenedione as a substrate in the presence of a fixed concentration of [14C] testosterone was found identical with the apparent Kd for the androstenedione as an effector (activator) for the oxidase function of the enzyme calculated from the simultaneous increase of [14C] androstnedione produced from the fixed concentration of [14C] testosterone. Similarly, the apparent Km of the oxidase function for [3H] testosterone as a substrate in the presence of a fixed concentration of [14C] androstenedione was identical to the apparent Kd for the testosterone as an effector (activator) for the reductase function of the enzyme calculated from the simultaneous increase of [14C] testosterone produced from the fixed concentration of [14C] androstenedione. None of the free 17-oxo and 17 beta-hydroxy steroids examined showed substrate activation or product inhibition of the enzyme except for androstenedione which showed product inhibition at high concentration. The present findings in combination with our previous data suggest the presence of two sites on the 17 beta-hydroxysteroid oxidoreductase of the human testis, one specific for androstenedione and the other specific for testosterone, each serving as an active site for the substrate and also as an activation site for the other active site. PMID- 6248334 TI - Various types of the pituitary folliculo-stellate cells involving the Siperstein's corticotroph in the normal rats. AB - The differentiation of the folliculo-stellate (F-S) cells was electronmicroscopically investigated in the normal male adult rats from the Wistar, Wistar-Imamichi, Holzmann, Spraque-Dowley and Donryu strains. The F-S cells may be divided into the five types according to the granulation. Each type is, however, provided with the common characteristic features, i.e., the stellate shape due to projecting the cytoplasmic processes and a tendency to embrace an acidophil. The first type is an agranular independent or anastomosing immature cell. It is different in shape and arrangement from the follicular cell, but similar in agranularity and immaturity to it. The second is a slightly differentiated cell, in which scanty small secretory granules 50--100 nm in diameter begin to appear near the plasma membrane. The third is a moderately differentiated cell providing the regularly row arrangement of secretory granules 100--200 nm in diameter along the plasma membrane, corresponding, in fine structure, with a corticotroph. The fourth is a fully differentiated cell with heavy granulation, whose secretory granules 150--250 nm in diameter are accumulated in the whole cytoplasm, suggesting the storing type. It is difficult to determine whether the fourth type coincides with a hypergranulated corticotroph or a stellate thyrotroph. The fifth is a kind of fully differenetiated cell which may refer to the releasing phase of the fourth type, being characterized by the dispersion or loss of minute secretory granules of low density as large as 50 nm in diameter, associated with the cored vesicles. The population densith of the above five types increased in the sequence, 5th leads to 4th leads to 1st leads to 3rd type in the gland. Namely, the 3rd (corticotroph) type and 1st (agranular) type are predominantly distributed, and the 5th (releasing) type and 4th (hypergranulated) type are rarely. PMID- 6248335 TI - In vitro steroidogenesis in testes of three infants, two with ambiguous external genitalia and one with true precocious puberty: Evidence for the presence of active 17 beta-hydroxysteroid oxidoreductase in immature human testes. AB - The present report investigated steroidogenesis in vitro in testis tissues obtained from two boys aged 8 months and 4 years with ambiguous external genitalia and male vagina, and a 4-year-old body with true precocious puberty. Histologically, testes of the former two boys are still immature and the testis of the last one contains differentiated Sertoli cells and primary spermatocytes, but no mature Leydig cells are recognized in any of them. In each testis, 17 beta hydroxysteroid oxidoreductase is active for androstenedione in the presence of an excess amount of NADPH, while delta 5-3 beta-hydroxysteroid dehydrogenase and delta 4-steroid 5 alpha-reductase activities are limited. 17 alpha-Hydroxylase and C17--20 lyase are significantly active in each testis and are enhanced in the testis of the boy with precocious puberty. Although the testis tissue used in the present study may not be biologically normal and the number of cases investigated is still limited, the above results indicate that active 17 beta-hydroxysteroid oxidoreductase is present in immature human testes and that delta 5-3 beta hydroxysteroid dehydrogenase may become active in the human testis at the advanced stage of the development of testicular function during the puberty. PMID- 6248336 TI - The effect of hypophysectomy and hypophysis-transplantation on the secretion of gut glucagon immunoreactivity and gut glucagon-like immunoreactivity in depancreatized dogs. AB - The role of hypophysis in the regulation mechanism of the secretion of gut glucagon immunoreactivity (gut GI) that was measured using C-terminal specific glucagon antiserum after pancreatectomy, and gut glucagon-like immunoreactivity (gut GLI) that was obtained by subtracting GI from total glucagon-like immunoreactivity (total GLI) which was measured using non-specific glucagon antiserum, was investigated in depancreatized dogs. Plasma glucose, gut GI and gut GLI levels were found to increase in totally depancreatized dogs. The former two showed a significant decrease after hypophysectomy, and were reversed by the hypophysis-transplantation, while gut GLI was not affected either by hypophysectomy or hypophysis-transplantation. Intramuscular injections of human growth hormone (HGH) or adrenocorticotropic hormone-Z (ACTH-Z) to depancreatized hypophysectomized dogs had no effect on plasma glucose level or gut GI. It is concluded that hypophysis may promote the secretion of gut GI after pancreatectomy, but not of gut GLI. Gut GI seems to regulate plasma glucose level after pancreatectomy. However, the precise regulation mechanism of gut GI by the hypophysial hormone after pancreatectomy is not clarified yet. PMID- 6248337 TI - A sensitive radioreceptor assay for follicle stimulating hormone with PMS-primed immature rat ovary. AB - After a single PMS (50 IU) injection to 25-day-old rats, FSH receptor content of the ovarian tissue increased progressively for 4 days, then showed a tendency to decrease, while LH receptor content remained unchanged for 3 days, then gradually increased. From these facts, we established a radioreceptor assay system, employing 3,000 rpm precipitates of homogenates of the ovaries obtained 3 days after PMS injection as the receptor preparation. The dissociahe standard curve was obtained with 0.125--16 ng/tube of NIAMDD rat FSH I-3. Purified preparations, NIAMDD rat LH I-4 and NIAMDD rat TSH I-4 influenced the binding only at high concentrations possibly owing to FSH contamination. When the anterior pituitary homogenates obtained from rats in the various physiological states were assayed by this system, the intra-assay coefficient of variation and inter-assay coefficient of variation were 7.5% and 13.7%, respectively, and the assay values were well correlated with those obtained by radioimmunoassay (r = 0.988, the slope of the regression line = 1.14). PMID- 6248338 TI - Dopamine-beta-hydroxylase. PMID- 6248339 TI - Catecholamine receptor supersensitivity and subsensitivity in the central nervous system. PMID- 6248340 TI - Bone scanning in the diagnosis of acute osteomyelitis. AB - Fifty-nine patients with suspected osteomyelitis were referred to the Nuclear Medicine Service for bone scanning during a twelve month period. The bone scan correctly identified abnormal sites in 18 of 19 patients with osteomyelitis (sensitivity of 95%) while the radiograph detected only 6 of 19 (sensitivity of 32%). In this clinical setting, the bone scans and radiographs had specificities of 92% and 89% respectively. Technetium-99m phosphate radiopharmaceuticals are superior to the previously used isotopes of fluorine and strontium in that they are readily available, can be imaged with conventional instruments, and allow high quality scans to be completed within 4 h. Routine bone scanning should be performed in patients presenting with suspected osteomyelitis and normal radiographs. The scan can be helpful in confirming or excluding the clinical suspicion and can lead to a more rapid institution of appropriate treatment. PMID- 6248341 TI - Accumulation of Tx-99m phosphonate complexes in metastatic lesions from colon and lung carcinomas. AB - Cases are presented in which Tc-99m methylene diphosphonate accumulated in a lung metastasis from well differentiated adenocarcinoma of the colon, and in a hepatic metastasis from oat cell carcinoma of the lung. To our knowledge, this is the first report of Tc-99m phosphonate complexes concentrated in a pulmonary metastasis of colonic caecinoma or in a hepatic metastasis of oat cell lung carcinoma. The exact mechanism for this non-osseous uptake of bone scanning agents is still unknown. PMID- 6248342 TI - Important factors in islet cell transplantation: the role of pancreatic fragments' size, pH, potassium concentration and length of intraportal infusion. AB - The role of pancreatic fragment size prior to collagenase treatment, pH, K+ concentration and length of intraportal infusion was studied in islet cell transplantation of streptozotocin-induced diabetic adult rats. This study demonstrates that pancreatic fragments of 1 mm prior to collagenase digestion, pH of 7.4, extracellular potassium concentration and 10 min of intraportal infusion are important factors in successful islet cell transplantation of adult rats receiving six donor pancreases for amelioration of chemical diabetes. These factors should be taken into consideration when consistent islet cell transplantation results are to be expected. PMID- 6248343 TI - Fine structural alterations in the aging rat pineal gland. AB - The pineal glands of 1 mo to 28 mo old male and female rats were examined by electron microscopy. With increasing age the following observations were made: (1) the capsule thickness increases; (2) there is an increase in collagen infiltration; (3) increased amounts of granular deposits are seen between cells; (4) there is a greater variability in the number of light pinealocytes; (5) pinealocytes with nuclear invaginations and pinealocytes with nuclear inclusions increase in number; (6) more cytoplasmic dense bodies are seen in pinealocytes and gliocytes; (7) the maximum diameter of pinealocyte lipid droplets tends to increase; (8) no definite change is observed in granular endoplasmic reticulum; (9) occasional cells are found to contain reticulated mitochondria, and a few cell processes have an appearance similar to neuroaxonal dystrophy. Besides illustrating age-rated changes, the present study proves the existence of pinealocyte nuclear inclusions, suggests the possibility of pineal concretions in the rat, and morphometrically or semi-morphometrically analyzes several structural features not previously quantified. PMID- 6248344 TI - Estradiol binding protein in cystosarcoma phyllodes of the breast. PMID- 6248345 TI - Distribution of intracisternal A particles in mouse teratocarcinoma-derived cell lines. PMID- 6248346 TI - Effect of mitogens and anti-bovine leukosis virus serums on DNA synthesis of lymphocytes from cattle. PMID- 6248347 TI - Inhibition of adjuvant arthritis by salbutamol and aminophylline. AB - Salbutamol (3 mg/kg) and aminophylline (75 mg/kg) were administered s.c. to rats separately or in combination after intradermal injection of adjuvant into the left hind paw. The paw volume was measured plethysmographically; tissue cyclic AMP content was determined by a protein binding assay following whole body microwave irradiation. The combination of salbutamol and aminophylline given daily significantly inhibited the swelling response in both the adjuvant-injected and the non-injected paws. This drug combination significantly increased the cyclic AMP levels in inflamed tissue of the adjuvant-injected hind paw and in lymphoid tissue such as the spleen and thymus. The combined treatment seems to have immunosuppressive as well as anti-inflammatory effects on adjuvant-induced arthritis. PMID- 6248348 TI - Modulation by histamine of peripheral vagal transmission in anesthetized mongrel dogs. AB - Intravenous infusion of histamine (6.0 microgram/kg/min) attenuated bradycardic responses to electrical stimulation of right vagus in anesthetized mongrel dogs. Similarily histamine also reduced reflexly mediated decreases in the heart rate to phenylephrine, while bradycardia induced by exogenous acetylcholine was not altered. This inhibitory action of histamine on responses to vagal stimulation could be antagonized by pretreatment with metiamide, an H2-receptor antagonist; but not by pyrilamine, and H1-receptor blocker. Metiamide significantly potentiated the negative chronotrophic effect of vagal stimulation. These results indicate that histamine could inhibit peripheral vagal transmission via a presynaptic action. The ability of histamine to alter vagal transmission may have physiological significance and play a role in histamine-induced tachycardia. PMID- 6248349 TI - Evidence for a presynaptic inhibitory action of 5-hydroxytryptamine on sympathetic neurotransmission to the myocardium. AB - A study was undertaken to determine the effect of 5-Hydroxytryptamine (5-HT) on sympathetic neurotransmission to the myocardium. Intravenous infusion of 5-HT (20 microgram/kg/min) produced a decrease in mean blood pressure and caused significantly impairment of cardioacceleration observed during the stimulation of right post-ganglionic cardiac sympathetic nerve. The pressor and tachycardic responses to norepinephrine as well as tyramine were potentiated during 5-HT infusion. The inhibitory effect of 5-HT on responses to cardiac nerve stimulation was not prevented by desipramine. Prior treatment with cyproheptadine prevented the depressor effect of 5-HT and significantly antagonized the inhibitory action of 5-HT on the positive chronotropic effect of cardiac nerve stimulation. Methysergide administration to a different group of dogs antagonized the effect of 5-HT on blood pressure, but did not alter the impairment of cardioacceleration caused by 5-ht during cardiac nerve stimulation. Neither cyproheptadine nor methysergide had any effect on the responses to cardiac nerve stimulation. These results suggest that 5-HT inhibits sympathetic neurotransmission of the myocardium via an action on 'trypaminergic' receptors which may be located on sympathetic nerve terminal and that these receptors can be selectively blocked by cyproheptadine but not by methysergide. PMID- 6248350 TI - Increase of myocardial pH by 1- and d-propranolol during ischemia of the heart in dogs. AB - Myocardial pH was measured continuously with a micro pH electrode inserted into the left ventricular wall in dogs. Anterior descending coronary flow was reduced to about 1/3 of the original flow by partial occlusion of the coronary artery. Myocardial pH decreased from 7.50--7.60 to 7.06--7.24 after partial occlusion. Drugs were injected intravenously during ischemia of the heart caused by partial occlusion. l-Propranolol (1 mg/kg) reduced heart rate and increased the pH from 7.06 +/- 0.04 to 7.48 +/- 0.04 (P less than 0.01). d-Propranolol (1 mg/kg) reduced heart non-significantly and increased the pH from 7.24 +/- 0.05 TO 7.56 +/- 0.05 significantly (P less than 0.05). In other studies, the effect of l- and d-propranolol on both heart rate and metabolic responses to isoproterenol (500 micrograms/kg i.p.) was studied. Isoproterenol increased heart rate and also elevated the blood levels of glucose and lactate. l-Propranolol inhibited these responses to isoproterenol. d-Propranolol did not inhibit the heart rate response but inhibited the blood lactate response to isoproterenol significantly. The blood glucose response to isoproterenol was inhibited by d-propranolol non significantly. The action of both l- and d-propranolol on ischemic myocardial pH may be related to their action on cardiac metabolism as well as to their local anesthetic action. PMID- 6248351 TI - Effects of divalent cations on neuromuscular transmission in the chick. PMID- 6248352 TI - A high affinity GTP binding site in rat brain. PMID- 6248353 TI - Solubilization of an active opiate receptor from Bufo marinus. PMID- 6248354 TI - Trypanosoma brucei: activities and subcellular distribution of glycolytic enzymes from differently disrupted cells. PMID- 6248355 TI - Plasmodium yoelii and Plasmodium berghei: isolation of infected erythrocytes from blood by colloidal silica gradient centrifugation. PMID- 6248356 TI - Ultrastructural and biochemical studies of the brain and other organs in rat after chronic ethanol administration. III. Influence of ethanol intoxication on oxidative phosphorylation of the rat brain mitochondria with ultrastructural and morphometric evaluation of mitochondrial fraction). AB - The effect of chronic ethanol intoxication on oxidative phosphorylation in the rat brain mitochondrial fraction was examined. Moreover, electron microscopy was used to verify the quantitative composition of the fraction and for examination of ultrastructural changes in the mitochondria. The experiments were carried out with 60 rats receiving, beside the normal diet, ethyl alcohol according to a modified RATCLIFFE model. In isolated rat brain mitochondria the NAD-dependent oxidation of substrates (glutamate + malate) was decreased. The phosphorylation index ADP/0 and the respiratory control ratio (RCR) in rat brain mitochondria from ethanol-treated rats were unchanged in the presence of both succinate and glutamate + malate. Chronic ethanol feeding did not induce any changes of succinate dehydrogenase and cytochrome oxidase activities in solubilised mitochondria fractions of rat brain. Electron microscopy studies revealed that mitochondria from control animals retained their outer and inner membranes, whereas those from rats given ethanol were almost always swollen and some were disrupted. In mitochondrial fractions isolated from ethanol-intoxicated rats an increase was observed of contaminating elements i.e. axons and synaptosomes of various sizes. It should be stressed that the mitochondria located inside synaptosomes and axons were unchanged. The composition of the fractions was quantitatively evaluated and confirmed the diminution of "free" mitochondria in the experimental fractions in favour of "bound" mitochondria which mainly occurred in the synaptosomes with preserved metabolic activity. On the basis of electron microscopy studies it could be suggested that ethanol intoxication causes the damage of some mitochondria, which become more sensitive to mechanical destruction during isolation procedure, and they do not sediment together with the fraction of normal ones. The absence of "free" mitochondria in pellets explains the spurious lack of disturbances in the energy metabolism of brain mitochondria after chronic ethanol intoxication. PMID- 6248357 TI - Low level chemiluminescence of the cytochrome c-catalyzed decomposition of hydrogen peroxide. PMID- 6248358 TI - Movement of endocytic shuttle vesicles from the sinusoidal to the bile canalicular face of hepatocytes does not depend on occupation of receptor sites. PMID- 6248359 TI - Evidence against the compartmentation of adenosine kinase and adenosine deaminase activities in human erythrocytes. PMID- 6248360 TI - Continuous monitoring of oxygen consumption and superoxide production by particle stimulated human polymorphonuclear leukocytes. PMID- 6248361 TI - Rotational dynamics of spectrin in solution and ankyrin bound in human erythrocyte membrane. PMID- 6248362 TI - Electron transport to nitrous oxide in Paracoccus denitrificans. PMID- 6248363 TI - The 25-hydroxycholecalciferol-1-hydroxylase activity of chick kidney cells: direct effect of parathyroid. PMID- 6248364 TI - Concanavalin A inhibits the basal and stimulated hormone release from pituitary cells in monolayer cultures. PMID- 6248365 TI - Implication of microtubules and microfilaments in the cyclic GMP response of rat exocrine pancreas to secretagogues. PMID- 6248366 TI - Excision sites in the GC clusters of the mitochondrial genome of yeast. PMID- 6248367 TI - Porcine peptide having N-terminal histidine and C-terminal isoleucine amide (PHI): vasoactive intestinal peptide (VIP) and secretin-like effects in different tissues from the rat. PMID- 6248368 TI - Demonstration of specific receptors for EGF--urogastrone in isolated rat intestinal epithelial cells. PMID- 6248369 TI - Improved method for the isolation of the A and A* proteins of bacteriophage phi X174. PMID- 6248370 TI - Molecular cloning of synthetic angiotensin 1 gene in Escherichia coli: a route to physiologically active hormone. PMID- 6248371 TI - Adenosine-5'(p-fluorosulfonylphenylphosphate) as a tool for investigation of cooperative properties of Na,K-ATPase. PMID- 6248372 TI - Separation of sendai virus glycoproteins by CM-Sepharose column chromatography. PMID- 6248373 TI - Collagen pro alpha 1 polysomes appear to sediment more rapidly than pro alpha 2 polysomes. PMID- 6248374 TI - Modulation of beta-adrenergic agonist binding by guanylnucleotides in avian erythrocytes. PMID- 6248375 TI - Receptors for 1,25(OH)2-vitamin D3 enriched in cloned osteoblast-like rat osteogenic sarcoma cells. PMID- 6248376 TI - Electrical manifestation of ion transport across black lipid membranes generated by a Na+/K+ ATPase. PMID- 6248377 TI - Slow GDP dissociation from the guanyl nucleotide site of turkey erythrocyte membranes is not the rate limiting step in the activation of adenylate cylase by beta-adrenergic receptors. PMID- 6248378 TI - Biosynthesis of cytochrome c oxidase in isolated rat hepatocytes. PMID- 6248379 TI - [Effect of microiontophoretic applications of cortisol on hippocampal neuronal activity in experiments on freely moving rabbits]. AB - In response to cortisole administration the majority of hormonesensitive hippocampal neurons increased ther firing rate in unrestrained rabbits. Apart from this, the hormone affected the interspike intervals distribution. Neurons with a lower spontaneous firing rate revealed a trend towards raise of hormone sensitivity. The data obtained corroborate the inhibitory role of the dorsal hippocampus in central mechanisms of regulation of hypophyseal corticotropic activity by the corticoids level. PMID- 6248380 TI - [Effect of neuropeptide fragments of adrenocorticotropic hormone and vasopressin on the behavioral activity of rats]. AB - The effects of vasopressin and those of fragments of adrenocorticotropin ACTH5 10; ACTH4-7; l-phenilalanin, and ACTH4-7 d-phenilalanin on the learning of rats in U-shaped labyrinth were studied. The consolidation of skills in long-term memory ability for reversal learning were checked. The results suggest that effect of all these oligopeptides on the higher nervous activity is significant and specific, vasopressin improving the long-term memory, ACTH4-7-l-phenilalanin improving the learning, ACTH4-7-d-phenilalanin making learning next to impossible. PMID- 6248381 TI - [Electrical activity of motor neurons of the vascularly perfused spinal cord of kittens]. AB - In 5--22-day kittens, using an original method of perfusion of the spinal cord and the hindlimb through arterial vessels, PSPs were intracellularly recorded from lumbar motoneurons of perfused cord during stimulation of dorsal roots, ventral columns or muscle nerves of the hindlimb. All synaptic actions were completely though reversibly abolished in Ca2+-free solution containing 1.5--2.0 mM Mn2+, indicating the chemical mode of transmission in these synapses. The addition of Mn2+ and removal of Ca2+ markedly reduced and eventually abolished the post--spike after--hyperpolarization of motoneurons without alteration of the spike height. In motoneurons the input resistance ranged from 1.3 to 15.1 Mom (5.9 Mon on the average). PMID- 6248382 TI - [Use of the voltage clamp technic to measure transmembrane ion currents in individual heart cells of a warmblooded animal]. PMID- 6248383 TI - [The effect of prostaglandins on steroidogenesis in isolated human and bovine adrenal cells: a study of the effect of the ACTH action mechanism (author's transl)]. AB - It has been reported that prostaglandins (PGs) stimulate steroidogenesis in the adrenal glands of various mammarian species. However, the exact role of PGs in steroidogenesis remains unclear. Therefore, attempts were made to clarify the action mechanism of PGs on steroidogenesis. The production of 11-OHCS in adrenal cells was stimulated by ACTH, PGE2 and PGF2 alpha. PGE2 increased the c-AMP level, but PGF2 alpha had no effect on it. No effect was observed by indomethacin or theophylline on the production of 11-OHCS by ACTH. Cycloheximide inhibited the elevation in 11-OHCS by PGE2 and PGF2 alpha. Different results were observed: PGs combined effects of varying concentrations of ACTH were additive, PGs-combine effects of varying concentrations of dbc-AMP were synergic, and simultaneous incubation of maximal concentrations of ACTH and PGs failed to elicit a supramaximal response. These results suggest that PGs act like ACTH on steroidogenesis in human and bovine adrenals and are in keeping with the hypothesis that the action of ACTH and PGs in steroidogenesis is Ca++ influx in the adrenal cells. PMID- 6248384 TI - [The inhibitory effect of tolbutamide on both secretions of cortisol in the adrenal cortex and of prolactin in the pituitary gland (author's transl)]. AB - It has been frequently postulated that insulin-induced hypoglycemia is widely employed clinically to assess the function of the hypothalamo-pituitary axis, being known to stimulate several pituitary trophic hormones such as HGH, ACTH, PRL (Prolactin), etc. Although tolbutamide produces hypoglycemia through the increase of endogenous insulin secretion, in the present study tolbutamide was used instead of insulin, and the effect of tolbutamide on the secretion of PRL from the pituitary gland and also on the secretion of cortisol from the adrenal cortex as well as HGH was studied, using 44 healthy normal subjects (male 35 and female 9, from 15 approximately 75 years of age). (1) PRL : One gram of tolbutamide injected into 5 normal subjects did not increase the serum concentration of PRL up to 120 minutes after the administration of the drug, while the concentration of PRL in the serum was increased clearly by the injection of insulin (0.1U/kg), with maximum PRL levels (approximately 50pg/ml) occurring at 60 minutes after the insulin administration. These results indicated strongly that tolbutamide inhibited the secretion of PRL from the pituitary gland. (2) Hypothalamo-Pituitary-Adrenal cortex : The same dose of tolbutamide as in the PRL experiment was also injected intravenously, and changes of serum cortisol levels were measured until 180 minutes after the injection of tolbutamide. It was found that levels of serum cortisol were clearly depressed within 30 minutes, and then the cortisol values started to increase up to 120 minutes after the administration of tolbutamide. The stimulatory effect of ACTH on the secretion of cortisol from the adrenal cortex was also strongly abolished by tolbutamide in the early phase as stated above. The data suggest that tolbutamide might have a direct inhibitory effect on the adrenal cortex as well as on pituitary PRL secretion. PMID- 6248385 TI - [Cyclic-AMP dependent protein kinase activity in the soluble thyrotropin receptor complex (author's transl)]. AB - The relationship between the thyrotropin (TSH) receptor and adenosine 3':5' monophosphate (cyclic-AMP) dependent protein kinase activity in bovine thyroid plasma membrane fraction was investigated. After solubilization of thyroid plasma membranes, the molecular sizes of TSH binding protein and protein kinase activities were compared using the sucrose density gradient technique. Cyclic-AMP dependent protein kinase activity was present in a soluble thyrotropin receptor fraction. The Km of this enzyme was 2.2 x 10(-6) M for casein substrate in the absence or presence of 10(-5) M cyclic-AMP. A [3H]-cyclic-AMP binding protein was also found in this fraction. The Ka for cyclic-AMP binding was 0.11 x 10(6) M-1, with 3 nmoles per mg protein of total binding capacity. After fractionation using a continuous sucrose density gradient, one of the several [125I]-bovine TSH binding peaks corresponded to a [3H]-cyclic-AMP binding peak. After fractionation on a sucrose density gradient containing 0.4 M NaCl at pH 6.5, a major peak of protein kinase activity was stimulated by adding 10(-5) M cyclic-AMP. A peak of [3H]-cyclic-AMP binding activity corresponded to the same peak. Protein kinase activity in the receptor fraction was stimulated by adding 6 mg/ml bovine TSH. The soluble TSH receptor fraction also had an adenylate cyclase activity stimulated by TSH. These results suggest that some TSH receptors in thyroid plasma membranes have associated adenylate cyclase activity and cyclic-AMP dependent protein kinase activity. The receptor, cyclase, and kinase activities may exist in a functional primary receptor unit which is a component of thyroid plasma membranes. PMID- 6248386 TI - [Studies on the thyrotropin receptor and adenylate cyclase activity in various thyroid diseases: I. The properties of TSH receptor and adenylate cyclase in Graves' thyroid and retro-orbital adipose tissues (author's transl)]. AB - Most current etiologic concepts of Graves' disease postulate that this is an autoimmune disorder. A humoral factor, such as thyroid stimulating immunoglobulin, may be the mediator. On the other hand, it has also been suggested that abnormalities in the thyroid gland itself might be responsible for hyperfunction of the gland in Graves' disease. The true etiology of Graves' disease is still unknown. Similarly, the pathogenesis of the ophthalmic changes of Graves' disease is obscure, but immune mechanisms figure prominently in current hypotheses of the pathogenesis. It has been suggested that human adipose cell membranes have TSH receptors and that antibodies reacting with the receptors may stimulate fat cells. In this study, we have evaluated TSH receptor and adenylate cyclase of Graves' thyroid glands. Furthermore, we have investigated those of retro-orbital and the other adipose tissues in the guinea pig and in man. Human thyroid tissues were obtained at surgery and immediately minced homogenized with a loose-fitting Dounce homogenizer. A part of 10,000 g pellet of the homogenate was used for adenylate cyclase assay. The rest of the pellet was further purified by a discontinuous sucrose gradient ultracentrifugation, and the plasma membrane fraction was used for the receptor assay. The 125I-TSH binding to the fraction was measured, and the affinity constant (Ka) and capacity (Ro) were obtained from Scatchard plots using Rosenthal's method of analysis. Normal thyroid tissue contained high affinity (Ka = 2.4 x 10(10) M-1; Ro = 0.9 pmole/mg protein) and low affinity (Ka = 1.9 x 10(8) M-1; Ro = 386 pmole/mg protein) receptors. The two orders of TSH receptor were also found in Graves' thyroid tissue. The affinity constant and capacity of high affinity receptors were identical with those of normal thyroids, but the affinity constant of low affinity receptors was lower in Graves' thyroid (P less than 0.05). The basal adenylate cyclase activity in normal thyroid tissues was 0.35 nmole/10 min/mg protein. The activity rose to 280% of basal with 166 mU/ml of TSH and 680% of basal with 10 mM of NaF. These values obtained in Graves' disease were not significantly different from the values of normal thyroids. It is concluded that thyroid hyperfunction in Graves' disease is probably not the result of an intrinsic abnormality of the TSH receptor-adenylate cyclase system. Human retro orbital adipose tissue was obtained at surgery from patients of Graves' exophthalmos or malignant neoplasm of accessory sinus. Guinea pigs tissue was obtained from 250g male animals. We were unable to demonstrate high affinity TSH receptor in human retro-orbital fat, perirenal fat or guinea pig retro-orbital fat. In contrast, guinea pig epididymal fat membranes showed TSH receptor characteristics similar to guinea pig thyroid membranes. In human adipose tissue, TSH did not stimulate the adenylate cyclase activity, although NaF definitely stimulated the enzyme... PMID- 6248387 TI - [Studies on the thyrotropin receptor and adenylate cyclase activity in various thyroid diseases: II. The properties of TSH receptor and adenylate cyclase in human thyroid tumors (author's transl)]. PMID- 6248388 TI - [Spiegler carcinomas with associated symptoms. A new syndrome? (author's transl)]. AB - The report concerns a southern Italian female patient of--at her death--67 years, who developed in 1975 within several months Spiegler basaliomas of the scalp. The tumors increased in size and number, and developed immediately to dedifferentiated, relapsing, metastasizing and finally lethal tumors which resisted to each therapy. Histologically only the structural rests of Spiegler basaliomas could be seen, but the cellular picture demonstrated completely dedifferentiated carcinomas. In this observation there was no dominant inheritance, as it is known in Spiegler basaliomas. The late manifestation of the tumors with immediate malignancy, the lacking affection of other members of the family, the high familiar incidence of internal carcinomas, and, finally, the combination with other associated symptoms (brachydactyly, racket nails, the latter ones also in the mother) revealed this disorder as a new syndrome of Spiegler carcinomas with associated symptoms. PMID- 6248389 TI - Acid and alkaline phosphatase in macrophages of Tenebrio molitor larvae stimulated with asbestos. AB - The authors studied the activity of acid and alkaline phosphatase in macrophages of Tenebrio molitor larvae stimulated with various types of asbestos: A and B chrysotile, crocidolite, amosite and anthophylite. The activity of the two enzymes increased, as did those of beta-galactosidase and N-acetyl-beta-D glucosaminidase, two previously assayed enzymes. The increase indicates the toxic action of various types of asbestos and correlates to variations in the mortality curves. The increases of the enzymatic activity and the macrophage response vary with the type of asbestos. PMID- 6248390 TI - Age-related histochemical and histological changes in the knee-joint cartilage of C57B1 mice and their significance for the pathogenesis of osteoarthrosis. I. Oxidative enzymes. AB - For a better understanding of the part played by the aging of cartilage in the pathogenesis ofosteoarthrosis, we attempted to detect functional age-related changes in the knee-joint cartilage of C57B1 mice using histochemical methods and to correlate these changes with the concomitant histological changes. A comparison of 57- and 97-week-old mice revealed a statistically significant age related focal loss of activity for a number of oxidative enzymes of the chondrocytes. There was an associated significant increase in regressive changes of the chondrocytes. A relation probably exists between these two changes, inasmuch as the focal loss of enzyme activity precedes and possibly gives rise to the regressive changes. A comparison with the changes described in the articular cartilage of other species including man suggests that the phenomena observed are inherent age-related changes. The loss of activity of all the enzymes investigated indicates a far-reaching derangement of cellular metabolism, leading to impaired synthesis of proteoglycans. Since these compounds are major determinants of the physical properties of articular cartilage, the changes described might render the cartilage more vulnerable and might thus play a major part in the pathogenesis of osteoarthrosis. PMID- 6248391 TI - Collagenase inhibitors retarding invasion of a human tumor in nude mice. AB - Tumor invasion has been correlated with the ability of tumor cells to produce collagenolytic enzymes which are capable of degrading normal host tissues. However, the human small cell carcinoma implanted subcutanouesly and growing progressively in athymic (nude) mice produced large quantities of collagenase but did not appear to significantly infultrate adjacent host tissue. In comparison, subcutaneously implanted murine Lewis lung tumors produced similar quantities of collagenase and were locally invasive. The human tumors were surrounded by a compact layer of fibroblast cells in a fibrous matrix. This fibrous sheath exhibited anticollagenase activity and indicated a mechanism of host tissue resistance to invasion via the formation of inhibitors to degradative enzymes produced by tumor cells. PMID- 6248392 TI - Inhibition of GABA binding by pyridoxal and pyridoxal phosphate. PMID- 6248393 TI - Plasma membrane-associated protein kinase activity of differentiating rabbit bone marrow erythroid cells. PMID- 6248394 TI - Partial purification of deoxyribonuclease II from human spleen. PMID- 6248395 TI - Comparison of fenoterol and orciprenaline with regard to broncho-dilating action and beta 2-selectivity. AB - A double-blind crossover trial was performed comparing orciprenaline (10 mg) and fenoterol (5 mg) by oral administration in forty-four patients with bronchial asthma. Measurement of VC, FEV1, respiratory impedance (ZR), blood pressure and pulse rate, and observation of subjective symptoms, rales, and side-effects, were made over the 4 hours following oral administration of the drugs. FEV1 increased through the 4 hours reaching a peak at 3 hours with both drugs. The per cent increase of FEV1 was statistically significant at each measuring time for both drugs (p less than 0.01), and was significantly larger in fenoterol than in orciprenaline at 2 and 3 hours (p less than 0.05). ZR with fenoterol decreased from 2 hours to 4 hours with a significant difference from ZR with orciprenaline (p less than 0.05). Side-effects such as palpitation, finger tremor or headache were seen in 36.4% cases with fenoterol and 30.5% with orciprenaline, but the degree of the side-effects was minimal. Finger tremor was observed in one case with orciprenaline and ten cases with fenoterol. Palpitation was observed in five cases with each of the drugs. Because finger tremor seems to be due to beta 2 stimulation and palpitation seems to be due to beta 1-stimulation, fenoterol was supposed to be more beta 2-selective than orciprenaline. In conclusion fenoterol had a high beta 2-selectivity and a powerful and long-lasting broncho-dilating effect compared with orciprenaline. PMID- 6248396 TI - Uncoupling of gonadotropin-sensitive adenylate cyclase by N,N' dicyclohexylcarbodiimide. Evidence for modification of two sites. AB - Treatment of purified rat ovarian plasma membranes with N,N' dicyclohexylcarbodiimide (DCC) abolishes the subsequent response of adenylate cyclase [EC 4.6.1.1, ATP pyrophosphate lyase (cyclizing)] to lutropin (LH) and follitropin (FSH) but not to NaF. Such treatment also inhibits binding to these membranes of iodinated [125I] human chorionic gonadotropin (125I-hCG). Preincubation for 30 min at room temperature with 70 microM DCC reduces the response of adenylate cyclase to LH by 50% whereas 4 times higher concentration is required to reduce 125I-hCG binding to the same extent. At 0.5 mM, DCC reduces both activities by 50% within 8-10 min. Preincubation of the membranes with hCG prior to treatment with DCC protects the hormone-binding site of the receptor but not the ability of the enzyme to respond to LH. Thus the enzyme becomes functionally uncoupled. It is suggested that at least two distinct sites in the enzyme system are affected by DCC. Both sites are located proximal to the regulatory step that involves GTP-binding protein. One site seems to be associated with the receptor and the second is located distal to receptor-hormone complex formation. PMID- 6248398 TI - Postnatal development of estradiol receptor in female and male rats. AB - The concentration of available cytoplasmic estradiol receptor was quantified in the postnatal hypothalamus and pituitary of male and female rats, aged from 4 to 28 days. The uterine receptor was measured in female rats. The method used was designed to avoid non-specific contamination of cytosol from very young animals by plasma proteins, especially alpha-feto-protein (AFP). In the hypothalamus, the concentration of estradiol binding sites was maximal 6 days after birth, and declined until day 28 to low constant level. In the pituitary, the estradiol receptor concentration increased from day 4 and reached a plateau at 13--14 days, whereas in the uterus, the concentration of cytoplasmic binding sites rose up to day 10--12, and then markedly decreased. PMID- 6248397 TI - Impairment of pituitary and gonadal functions in alloxan-induced diabetic male rats. AB - The inhibitory effect of treatment with a potent LHRH agonist on testicular gonadotropin-receptor levels was compared in intact and diabetic rats. Basal and LHRH-induced pituitary gonadotropin secretion as well as the testicular steroidogenic response to oLH were assessed. A single injection of alloxan (65 mg/kg) led, after 6 weeks, to a 40% decrease of testicular LH- and prolactin receptor levels. Treatment for 2 weeks with [D-Ala6,des-Gly-NH 1/2 0] LHRH ethylamide (100 ng every second day) led to a 70% reduction of LH-receptor levels accompanied by decreased testicular weight, a similar inhibition being found in intact and diabetic animals. Seminal vesicle and ventral prostate weight were markedly reduced in diabetic animals, a further decrease being obtained after treatment with the LHRH agonist. The loss of accessory sex-organ weight in alloxan-diabetic rats was accompanied by a reduction in the basal testicular content of pregnenolone, progesterone, 17-OH-progesterone, androstenedione, testosterone and dihydrotestosterone whereas the steroid response to oLH was within normal limits. We next examined the possible changes of LH and FSH secretion which could be responsible for the reduced testicular function in diabetic animals. Basal plasma-LH levels were 30% reduced in rats 6 weeks after treatment with alloxan while basal plasma-FSH levels remained unchanged. When the pituitary gonadotropin response to LHRH was measured in chronically cannulated freely-moving intact and diabetic rats, an approx. 50% inhibition of the LH and FSH responses to LHRH was observed in diabetic animals. PMID- 6248399 TI - Prostaglandin synthetase activity in bovine adrenocortical cells and subcellular preparations: effect of ACTH. AB - Prostaglandin (PGE2, PGF2 alpha) production by bovine fasciculo-reticulata adrenocortical cell suspensions was examined using specific radioimmunoassay procedures. No detectable PGs (greater than 50 pg) could be measured in the extract from up to 2 x 10(6) cell incubations after 1 h, with or without the presence of ACTH, although these cells expressed full steroidogenic capabilities under these conditions. The same preparations could produce PGs when supplemented with arachidonic acid but ACTH had no effect on this process. These negative findings could not be explained by analytical artifacts or metabolic transformation. However, an active PG synthetase system was characterized in bovine adrenocortical subcellular preparations. This system converted arachidonate and endogenous substrate(s) to PGE2 as the major product. No thromboxane or prostacyclin pathways were detected even at high enzyme/substrate ratio. Although the microsomal adrenal cortex PG synthetase activity shares many features with those observed in other tissues (Km = 8.3 x 10(-5) M, optimal pH at 8.0, stimulation of PGE2 formation in the presence of glutathione and L epinphrine), its specific activity was comparatively low (Vmax = 2.5 ng PGE2/min/mg microsomal proteins), which may explain our negative findings using cell suspensions. These findings do not provide evidence to support the hypothesis proposing a role of endogenous PGs in the mechanism of acute ACTH action in the case of bovine adrenal cortex. PMID- 6248400 TI - Protein phosphorylation: quantitative analysis in vivo and in intact cell systems. AB - Protein phosphorylation-dephosphorylation appears to be an essential component in the regulation of many cellular processes by hormones and drugs. This concept has developed primarily from in vitro biochemical studies in which various purified proteins have been phosphorylated and dephosphorylated by distinct protein kinases and phosphoprotein phosphatases. However, the more difficult, but essential, task of demonstrating the physiological occurrence of these reactions in intact tissue or cell preparations in many cases has not been undertaken in a quantitative manner. There are 4 basic approaches for assessing the extent of protein phosphorylation in vivo and in intact cell systems, each having particular advantages and disadvantages. These are summarized in Table 2. The applicability of any one procedure will be highly dependent upon the protein under investigation. For instance, chemical measurements of total protein-bound phosphate may provide only limited information for proteins which are phosphorylated at multiple sites but could be highly useful for those proteins such as glycogen phosphorylase which are phosphorylated at single sites. The relative ease and the high sensitivity of measuring 32P incorporation into proteins will tempt many investigators to rely heavily on this approach. It is a very powerful procedure, particularly for the initial identification of phosphoproteins, but ultimately quantitative conclusions regarding 32P incorporation must be corroborated by one or more of the other procedures. There is no simple, single experimental approach that may be used under all circumstances, but by integrating these procedures firm conclusions may be drawn regarding the physiological importance of phorphorylation of specific proteins. PMID- 6248401 TI - Kinetics of cAMP inhibition of DNA synthesis in bovine adrenocortical cells. AB - cAMP-treated bovine adrenocortical cells are arrested in the G1 phase of the cell cycle. Removal of serum also arrests bovine adrenocortical cells in G1. In the presence of cAMP, serum and fibroblast growth factor stimulate increases in medium cell volume, but DNA synthesis is not initiated. Under these conditions cAMP increases steroidogenic capacity 7- to 10-fold as assessed by metabolism of pregnenolone to fluorogenic steroids. When the kinetics of entry of cells into S phase are quantitated, serum- and FGF-treated cells initiate DNA synthesis at an exponential rate after a 12-h lag. In contrast when cAMP is removed, cells immediately initiate DNA synthesis without a lag at a similar exponential rate (6.3 and 5.3% of the cells entering S/h). In the presence of growth factors, cAMP treated bovine adrenocortical cells are thus hypertrophied with increased steroidogenic capacity, but are reversibly arrested at the G1/S boundary. These findings suggest that cAMP arrests cell replication by mechanisms distinct from those of serum deprivation. PMID- 6248403 TI - Interactions of gonadotropins with corpus luteum membranes. IX. Changes in the specific activities of some plasma-membrane marker enzymes in rat ovarian homogenates and purified membrane fractions at various times after priming with PMSG and hCG. PMID- 6248402 TI - Interactions of gonadotropins with corpus luteum membranes. VIII. The different properties of rat luteal cell light and heavy membranes cannot be explained by fractionation of inside-out and outside-out plasma-membrane vesicles. AB - Fractions enriched in luteal cell plasma-membranes were isolated from superovulated rat ovaries. Cell surface-membrane marker enzyme activities were measured in both light and heavy membrane fractions, with or without treatment with various detergents, to assess whether these fractions consisted of resealed vesicles with different orientations (i.e. inside-out or outside-out). Control and digitonin-treated membranes were also fractionated on sucrose-density gradients to monitor the buoyant density perturbation of each surface-membrane marker induced by this detergent. In another experiment, hCG-binding sites of superovulated rat ovaries were labelled in vivo by injecting [131I]hCG intravenously 2 h prior to fractionation and isolation of ovarian membranes. Membranes were then tested for the ability to bind [125I]hCG and [131I]hCG in vitro. These experiments indicated that light and heavy rat luteal cell membrane fractions had similar levels of inside-out membrane vesicles (ranging from 0 to 34%), and that the hCG-binding sites of the 2 fractions appeared to be equally freely accessible to hormone in vivo. It is concluded that differences in membrane orientation cannot account for the distinct properties and marker enzyme profiles of rat ovarian light and heavy membranes, providing further support that these membrane are derived from different regions of the luteal cell surface membrane. PMID- 6248404 TI - Stability of nuclear thyroid-hormone receptor and its behavior on hydroxylapatite. AB - Rat-liver chromatin was kept under several conditions. The maximum binding capacity (Bmax) and the apparent association constant (Ka) for triiodothyronine (T3)-binding were determined. Binding activity (Bmax x Ka) was unstable at 0 and 20 degrees C in the reaction buffer. Maximum binding activity was found upon storage at -70 degrees C or in liquid nitrogen where about 70% of the original activity remained after 3 weeks. With storage, Ka decreased more rapidly than Bmax which showed little change. These temperature-dependent changes in the stored chromatin were specific for the receptor and not observed for other characteristics of the chromatin, i.e., template activity and the electrophoretic separation pattern of chromatin proteins. The elution profile of the receptor on a hydroxylapatite column was unchanged during storage of the chromatin, suggesting that the chemical nature of the binding protein(s) may not change during storage. PMID- 6248405 TI - Changes in concanavalin A-mediated agglutinability of mouse oocytes during meiosis. PMID- 6248406 TI - Effect of cholecystokinin and pentagastrin on motility and gastric secretion in the cat. AB - The effects of cholecystokinin (CCK; 0.25-16 IDU kg-1h-1), synthetic octapeptide of CCK (OP-CCK; 0.5-2 microgram kg-1h-1) and pentagastrin (0.5-8 microgram kg-1 h 1) on pepsin secretion and antral motility were compared in conscious cats with reference to acid secretion. The results confirmed that the 3 peptides are full agonists for acid secretion and showed that they also displayed the same action on antral motor activity in increasing the frequency and decreasing the force of the contractions. Their effects on pepsin secretion were of different efficacy, decreasing from pentagastrin to CCK and to OP-CCK which showed a very weak action. PMID- 6248407 TI - Effects of gastrointestinal hormones and carbamylcholine on cAMP accumulation in isolated pancreatic duct fragments from the rat. AB - A modification of a technique to isolate kidney tubule fragments and pancreatic acinar cells has been used to prepare a suspension of pancreatic duct fragments from rats with pancreatic lipomatosis due to pretreatment with penicillamine and a copper-free diet. This suspension is 90-95% pure almost without any acinar cell contamination. The accumulation of 3',5'-cyclic adenosine monophosphate (cAMP) in response to various gastrointestinal hormones, hormone-like substances and theophylline was studied in these isolated pancreatic duct fragments. In the absence of theophylline, secretin increased the level of cAMP in a dose-dependent manner with a maximum at 10(-6) M. With supramaximal doses the concentration of cAMP decreased. During maximal stimulation with secretin the level of cAMP was dependent on the concentration of fragments in the incubation mixture. Vasoactive intestinal peptide (VIP) also increased the formation of cAMP. However, VIP was 10 times less effective than secretin on a molar basis. The addition of various concentrations of VIP to a submaximal dose of secretin did not alter cAMP levels as compared to the levels observed with the same concentration of secretin alone. Theophylline (5 x 10(-3) and 10(-2) M) stimulated cAMP accumulation and 5 x 10( 3) M theophylline potentiated the response to secretin and VIP. Pancreozymin (20 and 99% pure), glucagon bovine pancreatic polypeptide and carbamylcholine did not effect the level of cAMP when given alone or in combination with secretin. These data lend support to the hypothesis that cAMP is the intracellular mediator of the action of secretin and VIP on the pancreatic duct cells. PMID- 6248408 TI - Improved glucose tolerance four hours after taking guar with glucose. AB - To gain some insights about the possible cumulative metabolic effect after a high fibre meal, 6 subjects took two 80 g oral glucose loads, 4 h apart. Addition of 22.3 g guar to the first load decreased the rise in blood glucose and insulin after the second (guar-free) load by 50% (p less than 0.002) and 31% (p less than 0.02) respectively. This corresponded with decreased 3-hydroxybutyrate levels at the start of the glucose tolerance test after guar (by 20%, p less than 0.02). When no guar was added to the first glucose load, both 3-hydroxybutyrate and non esterified fatty acids tended to rise before the second test. No significant effect was seen in the responses of the gut hormones, gastric inhibitory peptide and enteroglucagon. Spreading the intake of the first 80 g of glucose over the initial 4 h (2 subjects) similarly flattened the glycaemic but increased the insulin response. The effect of guar on carbohydrate and fat metabolism, therefore, lasts at least 4 h and may result in improved carbohydrate tolerance to subsequent guar-free meals. PMID- 6248409 TI - The effect of streptozotocin-induced diabetes on the early steps of glucagon action in isolated rat liver cells. AB - This study was undertaken to investigate the effect of experimental diabetes on the early steps of glucagon action. The binding of glucagon and glucagon stimulated cyclic AMP accumulation in the presence of a potent phosphodiesterase inhibitor (IBMX, 0.1 mmol/l) were studied in liver cells isolated from control and streptozotocin-induced (65 mg/kg) diabetic rats. Comparative studies of insulin binding indicated that hepatocytes of diabetic rats bound twice as much 125I-insulin (10.8 +/- 2.0%) as those of control rats (5.7 +/- 1.3%). Scatchard analysis and the competition plots of the data suggested that this was due to an increased number of receptors rather a change in their affinity. No significant change was observed in 125I-glucagon binding of diabetic liver cells (5.8 +/- 0.5%( as compared to controls (6.8 +/- 0.4%). The number of molecules of glucagon bound to high and low affinity binding sites of control liver cells was (51 +/- 2) X 10(3) and (1300 +/- 134) X 10(3) sites/cell, respectively. The corresponding numbers in streptozotocin-treated rats were (45 +/- 5) X 10(3) and (1000 +/- 167( X 10(3) sites/cell, respectively. Cyclic AMP response to concentration of glucagon below 1 nmol/l was significantly lower in diabetics than in normals: for 0.3 nmol/l and 0.6 nmol/l of glucagon, cyclic AMP production was 48 +/- 7 pmol/10(6) cells and 78 +/- 8 pmol/10(6) cells in diabetics, as compared to 72 +/ 9 and 110 +/- 9 pmol/10(6) cells in normals. At concentrations of glucagon that are maximally efficient (greater than or equal to 7 nmol/l) cyclic AMP production was higher in diabetic (202 +/- 20 pmol/10(6) cells) than in normal rats (156 +/- 7 pmol/10(6) cells). Thus, diabetes seems to increase the quantity of adenylate cyclase and decrease its affinity for glucagon. Those changes are not related to a modification of the glucagon binding sites and are associated to an increase of insulin receptors. PMID- 6248410 TI - [Schistosomiasis clinically active for 25 years]. PMID- 6248411 TI - [Collagenase and hepatic cirrhosis]. PMID- 6248412 TI - On the origin of prostaglandin and its role in the sympathetic nerve transmission in vas deferens. PMID- 6248413 TI - The effect of cyclic dibutyryl adenosine 3',5'-monophosphate on mechanical activity and calcium movements of the smooth muscle of rat ileum and vas deferens. PMID- 6248414 TI - Inhibition by ouabain of the O2 consumption of mouse (Mus musculus) soleus and diaphragm muscles. PMID- 6248415 TI - Endocrine effects of castration followed by androgen replacement and ACTH injections in the male domestic duck (Anas platyrhynchos L.). PMID- 6248416 TI - The population biology of bacterial plasmids: a priori conditions for the existence of mobilizable nonconjugative factors. AB - A mathematical model for the population dynamics of nonconjugative plasmids that can be mobilized by conjugative factors is presented. In the analysis of the properties of this model, primary consideration is given to the conditions under which these nonself-transmissible extrachromosomal elements could become established and would be maintained in bacterial populations. The results of this analysis demonstrate the existence of conditions where, as a consequence of infectious transmission via mobilization, nonconjugative plasmids could become established and be maintained even when the bacteria carrying them have lower reproductive fitnesses than plasmid-free members of the population. However, these existence conditions are stringent and suggest therefore, that it is highly unlikely that plasmids of this type would become established and maintained without some direct selection favoring their carriage. The general implications of these results and limitations of the model are discussed. Brief consideration is also given to the implications of these theoretical findings to the problems of the spread of multiple antibiotic resistance plasmids (R-factors) and the risk of contaminating natural populations of bacteria with chimeric plasmids produced by work with recombinant DNA. PMID- 6248417 TI - DNA protection with the DNA methylase M . BbvI from Bacillus brevis var. GB against cleavage by the restriction endonucleases PstI and PvuII. AB - BamHI fragments of the Bacillus brevis var. GB plasmid pAD1 have been cloned in Escherichia coli HB101 using pBR322 plasmid as a vector. The analysis of the recombinant plasmids showed that additional PstI sites had appeared in cloned fragments of pAD1. Methylation of the recombinant plasmids in vitro by enzymes from B. brevis GB cells blocks cleavage at these additional PstI sites of cloned pAD1 fragments and at the PstI site of pBR322. Among DNA methylases of B. brevis GB, the cytosine DNA methylase M . BbvI is the most likely agent modifying the recognition sequences of PstI. The methylase can modify cytosine residues in PstI or PvuII sites if these recognition sequences are linked to G at 5'- or to C at 3'-termini. In particular, in vitro methylation of the SV40 DNA by B. brevis GB methylases protects one of the two PstI sites and two of the three PvuII sites. The described effect of the protection of the specific PstI and PvuII sites may be used for physical mapping of genomes and DNA cloning. PMID- 6248418 TI - Cloning vehicles for the homologous Bacillus subtilis host-vector system. AB - A series of Bacillus subtilis plasmids was constructed which carry either the leu region or both the leu and the dihydrofolate reductase (DHFR) regions of the B. subtilis chromosome. The DHFR-coding gene was derived from a trimethoprim resistant (Tmpr) B. subtilis strain, and cells harboring the DHFR plasmid showed resistance to trimethoprim (Tmp). One such leu+tmpr plasmid, pTL12, was found to be useful for cloning DNA fragments at the BamHI, EcoRI, BglII and XmaI sites. It was also shown that insertion of DNA fragments at the BamHI and XmaI sites of pTL12 inactivated the leuA gene function (insertional inactivation) but not tmpr, indicating that cells carrying recombinant plasmids can be detected easily by selecting Leu-Tmpr colonies. Combination of B. subtilis 168 and plasmid pTL12 should serve as an efficient homologous cloning system in B. subtilis. PMID- 6248419 TI - Enrichment of specific genes from genomic DNA or from clone library DNA, using R looping. AB - We have developed a procedure for enriching DNA for specific sequences that is based on R-looping (Thomas et al., 1976). R-loops are formed with the DNA using mRNAs containing the sequence of interest and then isolated on poly(U)-sepharose via the poly(A) tail of the mRNA. Model experiments showed that plasmid DNA containing a cDNA copy of an immunoglobulin kappa chain mRNA could be selectively retrieved using this procedure. Approx. 5-10% of the kappa sequences in mouse embryo DNA could be recovered by R-looping, while non-specific binding of mouse DNA to the poly(U)-sepharose column was 0.03-0.04%. This represents a 100-200 fold enrichment of mouse genomic kappa sequences. We have also used the procedure to rapidly screen a mouse clone library for immunoglobulin heavy chain genes. DNA from the clone library was enriched 100-200-fold using immunoglobulin heavy chain mRNAs, and the enriched DNA repackaged in vitro to recover the phage. PMID- 6248420 TI - Sequence of a yeast DNA fragment containing a chromosomal replicator and the TRP1 gene. AB - The DNA sequence of a 1.45 kb EcoRI fragment from the yeast (Saccharomyces cerevisiae) TRP1 region has been determined. The fragment contains the TRP1 gene and a yeast chromosomal replicator. The TRP1 gene has been located on the fragment by analysis of potential initiation and termination codons in the DNA sequence. This location has been confirmed by subcloning portions of the fragment. Both the 5' and 3' noncoding regions of the TRP1 gene contain sequence homologies with analogous areas surrounding other yeast genes. The yeast replicator has been localized in a region near the 3' end of the TRP1 gene. The DNA sequence in this region contains several structural features which may be involved in the initiation of DNA replication. PMID- 6248421 TI - Location of ribosome-binding sites in the nin5 region of bacteriophage lambda. AB - Seven ribosome-binding sites on DNA have been located within the region defined by the nin5 deletion as well as several ribosome-binding sites on each side of the nin5 region. These were mapped by electron microscopy relative to the end points of the nin5 deletion and two Tn903 transposons, one inserted into gene Rz and another inserted near gene Q. These ribosomes binding sites within the nin5 region may correspond to polypeptide initiation sites for up to seven new dispensible lambda genes. PMID- 6248422 TI - 3'-end labeling of DNA with [alpha-32P]cordycepin-5'-triphosphate. AB - Cordycepin-5'-triphosphate (3'-deoxyadenosine-5'-triphosphate) can be incorporated into the 3'-ends of DNA fragments using terminal deoxynucleotidyl transferase from calf thymus (Bollum, 1974). Because cordycepin-5'-monophosphate lacks a 3'-OH group, only a single residue is incorporated. Furthermore, DNA molecules that contain cordycepin-5'-monophosphate at their 3'-ends become resistant to hydrolysis by exonucleases that require free 3'-OH ends. As an alternative to 5'-end labeling of complementary DNA strands, we have used [32P]cordycepin-5'-triphosphate labeling of 3'-ends to confirm the nucleotide sequence of a HhaI-endonuclease-generated pTU4-plasmid DNA fragment that contains several hot spots for insertions of the transposable genetic element Tn3. 3'-End labeling with [32P] cordycepin-5'-triphosphate has also proved useful in determining the sequence of the pTU4 DNA in the vicinity of a strategically located SstII endonuclease cleavage site in the replication region of the plasmid. PMID- 6248423 TI - Appearance of beta-lactamase activity in animal cells upon liposome-mediated gene transfer. AB - A restriction fragment, 875 bp, which encodes for a beta-lactamase activity, was isolated from the Escherichia coli plasmid pBR322 DNA and entrapped in liposomes. The incubation of the DNA-liposomes with avian, murine, and human cultured cells results in the uptake of the DNA with the efficiency of around 2000 molecules per cell. Extracts of the recipient cells show a beta-lactamase activity as demonstrated by spectroscopic and microbiological methods. These results indicate the expression of a prokaryotic gene in eukaryotic cells. PMID- 6248424 TI - Cloning and characterization of 4.5S and 5S RNA genes in tobacco chloroplasts. AB - Tobacco chloroplast 4.5S and 5S RNAs were shown to hybridize with a 0.9 . 10(6) dalton EcoRI fragment of tobacco chloroplast DNA. Recombinant plasmids were constructed from fragments produced by partial digestion of the chloroplast DNA with EcoRI and the pMB9 plasmid as a vector. Five recombinants containing the 4.5S and 5S genes were selected by the colony hybridization technique. One of these plasmids contained also the 16S and 23S RNA genes and was mapped using several restriction endonucleases as well as DNA-RNA hybridization. The order of rRNA genes is 16S-23S-4.5S-5S and the four rRNA genes are coded for by the same DNA strand. PMID- 6248425 TI - Construction and characterization of E. coli promoter-probe plasmid vectors. II. RNA polymerase binding studies on antibiotic-resistance promoters. AB - The binding of Escherichia coli RNA polymerase to antibiotic-resistance promoters was examined using the nitrocellulose filter assay. Four filter-retainable HaeIII fragments were observed with pBR322 and the promoter-probe plasmids, pBRH1, pBRH2 and pBRH4. Of the three fragments studied, two were shown to carry promoters for the ampicillin (Ap) and tetracycline (Tc) resistance genes, while the third present in pBRH1 appears to be the promoter for colicin E1 immunity (Colimm). Although the formation of filter-retainable complexes involving the Tcr promoter was sensitive to high salt, Apr promoter complexes were not. It was also shown that plasmids containing only the "firm-binding" portion of the Tcr promoter could still bind RNA polymerase in vitro despite the fact that these plasmids confer no in vivo Tcr. Additional filter-binding experiments performed with AluI digested pBR322 DNA revealed the presence of a fifth RNA polymerase binding site on pBR322. This site is probably the promoter for the 100 bp transcript thought to be involved in the initiation of plasmid replication. An analysis of the recombinant plasmid (pKTR25) which carries the Kan-B portion of the EcoRI kanamycin (Kn) resistance fragment revealed that this fragment contains two RNA polymerase binding sites. We believe that these sites are responsible for the insertional activation of the Tcr gene and may be the promoters for the Knr and fusidic acid (Fa) resistance genes. PMID- 6248426 TI - Recognition sequence for the restriction endonuclease BglI from Bacillus globigii. AB - Restriction endonuclease BglI recognizes the DNA sequence (Formula: see text) and cleaves each strand at the site indicated, thus generating 3' protruding ends. The recognition sequence was deduced by correlating mapping data with nucleotide sequence information and the position of cleavage was unambiguously determined by 32P labeling of 5' termini produced by BglI digestion. PMID- 6248427 TI - The DNA sequence recognised by BglI. AB - The restriction enzyme BglI recognizes the DNA sequence: (Formula: see text) and cleaves it in the position shown by the arrows to leave 3' single-stranded protrusions three bases long. PMID- 6248428 TI - The recognition site of type II restriction enzyme BglI is interrupted. AB - The Type II restriction endonuclease BglI recognizes the interrupted DNA sequence 5'-G-C-C-N-N-N-N-N-G-G-C-. This sequence occurs at all locations in over 33 000 base pairs of DNA sequence where the enzyme was found to cut DNA and nowhere else. All six of the specified bases are essential parts of the site since all groups of five of the six bases occur in the DNA sequences tested and none of them are cut by BglI. The length of the block of intervening unspecified positions must be exactly five since all other sizes between zero and 15 occur in the DNA sequences searched and none are cut by BglI. The 5'-terminal nucleotides of BglI cleaved phage G4 replicative form DNA and plasmid pER18 DNA were compared with the DNA sequences near the BglI sites on these DNAs. These results indicated that BglI cuts within the intervening unspecified region and produces single stranded 3' termini that are three bases long. The BglI recognition site and cleavage points can thus be represented as follows: (Formula: see text). This study of the BglI recognition site was facilitated by the use of inexpensive microcomputers. A system of programs was developed that allowed analysis of over 33 kb of DNA sequences stored on flexible magnetic disks or audio cassettes. While these programs were generally written in the higher level language BASIC, some assembly language subroutines were utilized to reduce execution time. PMID- 6248429 TI - Aminoglycoside-modifying enzymes of Staphylococcus aureus; expression in Escherichia coli. AB - Staphylococcus aureus plasmids PSH2, RN1956 and pWA1 code for an aminoglycoside phosphotransferase; plasmid pWA1 also encodes an aminoglycoside-aminocyclitol adenylyltransferase. S. aureus plasmid pWA2 confers resistance to erythromycin and sulfonamide. Using plasmid ColE1-ApR (RSF2124) as a vehicle, we have transferred the genes determining aminoglycoside phosphotransferase and aminoglycoside-aminocyclitol adenylyltransferase activities from S. aureus to Escherichia coli. The new plasmids obtained confer aminoglycoside-aminocyclitol resistant phenotypes to E. coli, similar to, and by the same mechanisms as "naturally" occurring plasmids. By contrast, the results obtained after cloning of plasmid pWA2 indicate that certain S. aureus antibiotic resistance determinants (e.g. for erythromycin (Em) and sulfonamide (Su) cannot be phenotypically expressed in E. coli. The DNA of the constructed hybrid plasmids has been analysed by agarose gel electrophoresis following digestion with restriction endonucleases, by ultracentrifugation in cesium chloride, by hybridization, and by electron microscopy. Each hybrid is a cointegrate replicon, composed of an entire S. aureus plasmid covalently joined to ColE1-ApR. PMID- 6248430 TI - Construction and characterization of new cloning vehicles. IV. Deletion derivatives of pBR322 and pBR325. AB - In vitro recombinant DNA experiments involving restriction endonuclease fragments derived from the plasmids pBR322 and pBR325 resulted in the construction of two new cloning vehicles. One of these plasmids, designated pBR327, was obtained after an EcoRII partial digestion of pBR322. The plasmid pBR327 confers resistance to tetracycline and ampicillin, contains 3273 base pairs (bp) and therefore is 1089 bp smaller than pBR322. The other newly constructed vector, which has been designated pBR328, confers resistance to chloramphenicol as well as the two former antibiotics. This plasmid contains unique HindIII, BamHI and SalI sites in the tetracycline resistance gene, unique PvuI and PstI sites in the ampicillin resistance gene and unique EcoRI, PvuII and BalI sites in the chloramphenicol resistance gene. The pBR328 plasmid contains approx. 4900 bp. PMID- 6248431 TI - Cloning DNA restriction endonuclease fragments with protruding single-stranded ends. AB - A new method of in vitro recombination was employed to construct plasmids containing lac promoter fragments 64 bp and 144 bp long. The 64 bp HpaII-HhaI fragment contains the binding site for the catabolite activator protein (CAP). The HpaII-HaeIII 144 bp fragment includes the binding sites for RNA polymerase, the lac repressor and CAP. The method utilizes the ability of T4 DNA polymerase to make flush-ended DNA either by filling in a recessed 3'-end or by exonucleolytic removal of a protruding 3'-end. The treated fragments were then blunt-end ligated to the filled-in EcoRI cloning sites of the plasmids pVH51 and pBR322 using T4 ligase. In this process, the EcoRI sites were regenerated on the fragment ends thus facilitating the subsequent isolation of the fragments from their cloning vectors. PMID- 6248432 TI - Kallikrein-kinin system and adenosine metabolism system of blood and heart and their changes at hypothalamic-hypophyseal stimulation in rabbits of different age. AB - It was shown that kallikreinogen content was decreased in blood of old rabbits, kallikrein activity was somewhat increased, kininase activity was significantly decreased. In old animals, adenosine metabolism was activated, this being evident from the rise of 5'-nucleotidase and adenosine deaminase activity in blood and myocardium. Hypothalamic stimulation resulted in significant activation of the kallikrein-kinin system and sharp increase of kallikrein activity, the shifts being less marked in old animals than in adults. In adult animals, vasopressin administration elicited more marked activation of the kallikrein-kinin and adenosine metabolism systems. PMID- 6248433 TI - [Methods of isolating intestinal and respiratory viruses from various environmental objects]. PMID- 6248434 TI - [Hygienic standard for silica-containing dust in the atmosphere of populated places]. PMID- 6248435 TI - [Activity of 5'-nucleotidase and alkaline phosphatase (AP) in the blood serum in early puerperium]. PMID- 6248436 TI - [Course and curability of malignant mesodermal mixed tumors of the uterus]. PMID- 6248437 TI - [Glucocorticoids in the perinatal period]. PMID- 6248438 TI - Endocrine profile and therapeutic employment of a new prolactin-lowering drug, metergoline. PMID- 6248439 TI - Specialization of the tubal epithelium and blastomere mitochondria in the rat. PMID- 6248440 TI - Ethambutol neurophathy: clinical and electroneuromyographic studies. AB - Clinical features including changes in the peripheral nerve conduction were analzyed in 10 cases with ethambutol neuropathy. There were abnormalities in the visual field in seven and optic atrophy in five of 10 cases. Seven of 10 cases complained of numbness in the lower limbs. The age of onset and dose of ethambutol the patients continue to take after the occurrence of visual impairment were found to be important in determining the severity of neurological symptoms. A functional disturbance was more conspicuous in ethambutol neuropathy, particularly in the sensory system than in the motor system so far as the peripheral nerve conduction was serially examined. Some cases still had serious optic disturbances even about seven years after the onset of the disease and the presence of irreversible lesions was suspected. PMID- 6248441 TI - Peripheral nerve conduction function in patients treated with antituberculotic agents, with special reference to ethambutol and isoniazid. AB - The electrophysiological examination was made to clarify the effect of ethambutol on the peripheral nervous system in 39 patients at tuberculous sanatorium. Abnormalities in the sensory nerve action potential (toe-ankle) were observed in about 10 percent of the patients treated with ethambutol, and these patients were mostly elderly and/or received the high dose of ethambutol. The mixed nerve conduction velocity (ankle-knee) showed a significant decrease compared with healthy subjects. The conduction velocity tended to decrease in the high ethambutol dosage (200 gm or more) group compared with the low dosage (200 gm or less) group. The tendency for the conduction velocity to decrease was also observed in the 18 patients treated with isoniazid but the abnormalities were mild compared with the ethambutol. PMID- 6248442 TI - Plasma cyclic AMP level in psychiatric diseases of childhood. AB - Determinations were made of the plasma cyclic AM level to examine its relationship with hyperkinesis (Werry-Weiss-Peters Activity Scale, WWPAS) and other features of mental disorders in 80 children, of whom 21 had early infantile autism, 15 hyperkinetic mental retardation, 12 minimal brain dysfunction and 32 Down's syndrome. In autistic and hyperkinetic mentally retarded children, the plasma cyclic AMP levels were higher than in normal children and were positively correlated with the WWPAS score. In children with minimal brain dysfunction, the plasma cyclic AMP level was significantly lower than in normal children and was not correlated with the WWPAS score. In children with Down's syndrome, the plasma cyclic AMP level was somewhat higher than in normal children. PMID- 6248443 TI - Differences of opinion over TDI. PMID- 6248444 TI - [The angiographic diagnosis of islet cell tumours. Results in 34 patients (author's transl)]. AB - Between 1965 and 1979, 34 patients with organic hyperinsulinism were examined angiographically. By observing the following points it should be possible to diagnose tumours greater than 1 cm, whatever their position in the pancreas: 1) Use of high performance generators and tubes which permit one to employ fine focus, low kv and high mAs. 2) Optimum imaging systems (carbon fibre table top, high intensity screens). 3) Selective catheterisation, large quantities of contrast per unit time and adequate duration of the filming sequence. 4) Pharmacoangiography and subtractions may be valuable in some cases. PMID- 6248445 TI - Regulation by vitamin D of intestinal phosphate absorption. PMID- 6248446 TI - No effect of starvation on vasoactive intestinal peptide (VIP) receptors in intestinal epithelial cells. PMID- 6248447 TI - Presence of ganglion cells in Wilm's tumours: a review of the possible neuroepithelial origin of nephroblastoma. AB - Twenty-seven cases of Wilms' tumour were reviewed in order to confirm the presence of nervous tissue which could imply a 'neuroepithelial' origin for these neoplasms. For this purpose a double-silver impregnation technique was used. Groups of ganglion cells with neurofibrils and non-myelinated axon-like processes appeared associated with a fine neurofibrillar network with neuromuscular junctions. Nervous tissue in nephroblastoma is mature and should not be confused with primary ganglioneuroblastoma of the kidney in which neuroblasts in rosette like groupings are very numerous. A case report of such a lesion is discussed for purposes of comparison. PMID- 6248448 TI - Where is the gene for GALT? PMID- 6248449 TI - Assignment of the human gene for phosphoglycolate phosphatase to chromosome 16. AB - Seventeen independently derived primary mouse-human hybrid clones were scored for the expression of human phosphoglycolate phosphatase (PGP) by electrophoresis and for the presence of human chromosomes with the aid of Q banding. The correlation of biochemical and cytogenetic analyses shows that the segregation of human PGP in these hybrids is concordant only with human chromosome 16, thus enabling the assignment of the genetic locus for PGP to human chromosome 16. PMID- 6248450 TI - Galactose-1-phosphate-uridyltransferase (E.C. 2.7.7.11): a simple routine method for detecting individuals heterozygous for the silent allele Gt 0. AB - A simple routine method for detecting individuals who are heterozygous for the silent gene Gt 0 is presented. This method consists of a combination of electrophoresis and densitometry. The results confirm the theoretical expectation that these individuals would exhibit about 50% of the enzyme activity found in the corresponding normal phenotype. PMID- 6248451 TI - Effect of silica on the proliferative behavior of human lung fibroblasts. AB - We show that silica enhances the proliferation of some but not all lung derived fibroblastlike cells (FLC) of fetal and adult origin. Cultures were obtained from lung biopsy and lavage of normal individuals and patients with interstitial lung disease. The responses of these cell lines were heterogeneous; some cultures were stimulated to proliferate in the presence of silica and others were not stimulated. There was no apparent correlation between source of the cell lines and the effects of silica. The proliferative capacity of the cells appeared to be an important determinant of the effect of silica on the growth of the cultures. PMID- 6248452 TI - Adenylate cyclase and phosphodiesterase activities in rat hepatocytes cultured in the presence and absence of dexamethasone. AB - The effects of glucagon and dexamethasone on the activities of the enzymes involved in cyclic adenosine 3':5'-monophosphate (cyclic AMP) metabolism in primary monolayer cell cultures of adult rat hepatocytes were examined. Short term experiments indicated that the magnitude of the cultured cells' response to glucagon, as measured by production of cyclic AMP, was essentially the same as that for freshly isolated hepatocytes. However, the time course of this response was markedly different. Although the activity of adenylate cyclase is maintained throughout the culture period at a level similar to that of the freshly isolated hepatocytes, the activity of both low and high Km forms of phosphodiesterase decreases rapidly with length of time in vitro. This is reflected by an increase in cyclic AMP produced in response to glucagon and theophylline by cells of different ages. Dexamethasone caused an increased loss of phosphodiesterase activity, as well as increased cyclic AMP accumulation in the presence or absence of theophylline. Various agents failed to restore the lost phosphodiesterase activity. These results may indicate that phosphodiesterase activity is more sensitive to the inevitable inadequacies of the in vitro environment of cultured hepatocytes than adenylate cyclase. It was also found that a modification of the method of Seglen (1) for the preparation of isolated hepatocytes yielded cells that had less phosphodiesterase activity than those prepared by the method of Berry and Friend (2). PMID- 6248453 TI - Lymphoid cell line identification and the detection of cross contamination. AB - Four lymphoid cell lines, presumably recent derivatives from non-neoplastic human tonsils, were identified in actuality as established Burkitt lymphoma and lymphoblastoid cell lines (LCL) when tested by chromosome banding and typing for HLA antigens. Additionally, the morphology, growth characteristics, tumorigenicity, expression of Epstein-Barr virus antigens and surface membrane immunoglobulins (SmIg) of the four lymphoid cell lines confirmed the correct identifications. In determining the possibility of cross contamination, the most reliable criteria for the identification of lymphoid cell lines were found to be HLA antigenic profile, karyotype, cellular morphology, and growth characteristics. PMID- 6248454 TI - Effect of cell-substratum interaction on hemicyst formation by MDCK cells. AB - On impermeable substrata MDCK cells, a cell line derived from normal dog kidney, forms a confluent monolayer that is studded with numerous hemicysts. Previous studies with this cell line suggest that thes hemicysts develop as a result of active fluid accumulation between cell sheet and substratum. However, the formation of hemicysts as a multifocal phenomenon is still unexplained. The results presented here show that the hemicysts are not only expressions of active transport of solutes and water, but also of cell-substratum interaction. The increase in number and size of the hemicyst produced by dbcAMP may be explained by a decrease in the adhesive strength to substrata produced by this compound. Moreover, when the strength of the cell-substratum adhesion was increased the number of hemicysts was reduced or abolished. On the contrary, when this strength was reduced, larger hemicysts occurred, covering practically all the area available for growth. Results from cinematographic time lapse studies, showing that 90% of the area of the monolayer is able to produce hemicysts, also suggest that hemicyst formation as a multifocal phenomenon is more an expression of local variations in cell-substratum interaction than of regional changes in transepithelial active transport. PMID- 6248455 TI - Calcium, magnesium, and serum factors in multiplication of normal and transformed human lung fibroblasts. AB - Serum factors determine the extracellular requirement for both Ca2+ and Mg2+ for multiplication of normal human lung fibroblasts in vitro. Serum factors also affect the extracellular Ca2+ requirement for transformed fibroblasts but to a different extent than for normal cells. Transformed cells exhibit a reduced requirement for both Ca2+ and Mg2+ for multiplication. The apparent reduction in Ca2+ requirement of transformed cells is dependent on the level of serum factors in the medium. The reduced Mg2+ requirement for transformed cells is more striking than the loss of Ca2+ and independent of the level of serum factors in the medium. A sequential effector relationship among serum factors, Ca2+ and Mg2+, in a proliferative control system for normal cells is proposed. Alteration or bypass of an intracellular Mg2+-requiring process is proposed as a major lesion in the transformed cells. This alteration causes an observed loss of requirements for both Ca2+ and serum factors for the multiplication of transformed cells. PMID- 6248456 TI - Effect of an intrauterine copper device on the enzyme activity of rat endometrium. PMID- 6248457 TI - Biological behaviour & antigenicity of mouse passaged & formol inactivated foot & mouth disease virus type Asia-1 in guineapigs. PMID- 6248458 TI - Role of adrenergic receptors on asphyxic vasopressor response. PMID- 6248459 TI - Prolactin involvement in the maintenance of ovarian lutropin receptors in lactating rat. PMID- 6248460 TI - Enzyme linked immunosorbent assay (ELISA) using beta-lactamase for the detection of antibodies to KFD virus. PMID- 6248461 TI - Typing herpes simplex virus antibodies by complement-dependent antibody lysis of infected cells. PMID- 6248462 TI - Effects of long-term blockade of angiotensin converting enzyme with captopril (SQ14,225) on hemodynamics and circulating blood volume in SHR. AB - Male spontaneously hypertensive rats (SHR), 13 weeks old, received oral administration of captopril (SQ14,225) daily at a dose of 10 mg/kg or 30 mg/kg; or water at 2 ml/kg, for 6 weeks. Captopril suppressed the development of hypertension slightly at the lower dose and completely at the higher dose. At 6 weeks of dosing, hemodynamic parameters were measured by the tracer microsphere method and blood volume by the dilution method using 51Cr erythrocytes. Cardiac output (CO) increased and mean blood pressure decreased in a dose-dependent manner; thus, total peripheral resistance decreased. Cerebral and renal blood flows increased in a dose-dependent manner while blood flow to other organs tended to increase or remained unchanged. There was no significant differences in the circulating blood volume among the three groups. In conclusion, long-term blockade of angiotensin converting enzyme (ACE) with captopril dilated blood vessels in the whole body, especially in the brain and kidney, and lowered blood pressure without causing plasma expansion or tachycardia. PMID- 6248464 TI - Initial kinetics of lysosomal enzyme secretion and superoxide anion generation by human polymorphonuclear leukocytes. AB - Human polymorphonuclear leukocytes (PMN) exposed to particulate and soluble stimuli secrete lysosomal enzymes. These stimuli cause prompt (less than 10 sec) changes in membrane potential followed 30--45 sec later by superoxide anion (O 2.) production. We describe a new technique utilizing flow dialysis apparatus which monitors the first stages of lysosomal enzyme release with a resolution of approximately 6 sec. Secretion of beta-glucuronidase from cytochalasin B-treated PMN could be detected 19+/-5 sec after exposure to the chemotactic peptide N formylmethionylleucylphenylalanine (FMLP). The "lag" times for release of this enzyme were different for other stimuli: 35+/-8 sec (BSA/anti-BSA immune complex); 48+/-8 sec (serum-treated zymosan, "STZ"); 60+/-25 sec (calcium ionophore A23187). The lag times for lysozyme release were less dependent upon the stimulus presented (28+/-16 sec for FMLP, 28+/-8 sec fo BSA/anti-BSA, 32+/-10 sec for STZ, and 38+/-8 seconds for Con A); only A23187 had a long lag period: 74+/-27 sec. Lag periods for the onset of O-2. production (measured by the same mathematical criteria) were comparable to those for beta-glucuronidase release: 21+/-4 sec for FMLP, 43+/-14 sec for BSA/anti-BSA, 62+/-7 sec for Con A, and 50+/ 13 sec for A23187. Changes in FMLP dose up to 100-fold affected the magnitudes of O-2. generation and beta-glucuronidase release, but did not alter the time required for the onset of these processes. A variety of agents, such as corticosteroids, colchicine, 2-deoxyglucose, and N-ethyl maleimide, also affected the magnitudes of the responses, but not the lag periods when FMLP was used as the stimulus. When BSA/anti-BSA immune complex was used as the stimulus, 2 deoxyglucose and N-ethyl maleimide increased the lag period for superoxide anion generation, but not for lysosomal enzyme release. This new flow dialysis technique has permitted us to demonstrate the O-2. production and lysosomal enzyme secretion are concurrent but dissociable processes which are subsequent to earlier responses of the granulocyte-to-ligand-receptor interactions as reflected by changes in membrane potential. PMID- 6248463 TI - Evidence that OH. production by human PMNs is related to prostaglandin metabolism. AB - Recent studies indicate that human granulocytes generate OH. during the phagocytosis of zymosan particles. Several theoretical considerations suggested to us that this OH. production might be related to prostaglandin metabolism, particularly the observation that OH. is generated by the reducation of hydroperoxides in microsomal systems. In our studies, we tested the importance of prostaglandin metabolism in the production of OH. by human granulocytes (PMNs). Indomethacin and aspirin at concentrations known to impair cyclooxygenase activity decreased OH. production by PMNs during the phagocytosis of zymosan particles. Phenol, which is known to alter prostaglandin metabolism, ablated OH. completely. None of these drugs at the concentrations used impaired the generation of O-2 or H2O2 by PMNs, as indicated by their failure to diminish significantly the generation of chemiluminescence. Thus, the decrement in OH. production by these drugs could not be attributed to a nonspecific effect on the production of O-2 or H2O2. These experiments therefore, indicate that the model for OH. production observed during prostaglandin synthesis with microsomal systems applies to human granulocytes. PMID- 6248465 TI - A two year serological surveillance of coronavirus infections in Hamburg. AB - The occurrence of OC-43 coronarvirus-like infections in the population of Hamburg was determined by a monthly serological survey (hemagglutintion inhibition test [HI]) undertaken between October 1974 and October 1976. Studies of 3,016 sera revealed a high incidence of HI antibodies (58,2%). The frequency of seropositive reactions (= 1:8) and the geometric mean titer were higher in individuals 15 to 24 years old. Treatment of 50 postive sera (titer 1:16 -1:64) with receptor destroying enzyme, kaolin and ethacridin for elimination of nonspecific inhbitiros did not modify the HI-titer of the investigated sera. The serological seasonal pattern suggests that coronaviruses are circulating the whole year in the urban population with a prevlence in the fall-winter period. Of the 331 paired sera examined, 6.6% presented a four- to eightfold rise intiter within eight weeks. PMID- 6248466 TI - Evidence for type-C retrovirus production by Burkitt's lymphoma-derived cell line. AB - Burkitt's lymphoma cell line, P3HR-I, was found to secrete virions with properties of known type-C RNA tumor viruses. The viral particles had a buoyant density of 1.16 g/ml in sucrose gradients and contained a high-molecular-weight RNA and an RNA-instructed DNA polymerase. The viral polymerase was active in an endogenous reaction requiring the presence of the four deoxyriboside triphosphates and manganese ions, and was sensitive to RNase. The DNA product of the endogenous reaction specifically hybridized to P3HR-I viral 60 to 70S RNA. Electron microscopic examination of ultrathin sections of P3HR-I cells revealed immature, mature and budding virions typical of type-C retroviridae. Nucleic acid hybridization assays showed no sequence homoblastosis virus, murine oncornaviruses, simian sarcoma virus or RD114 virus. PMID- 6248467 TI - Age- and tumor-correlated changes in functional antibody responses to MTV in neonatally infected mice. AB - BALB/cfC3H female mice (neonatally infected with MTV) possess several different specific antibody activities measured functionally by reactivity with MTV associated antigens expressed on the surface of isologous MTV-induced mammary tumor target cells. All females when young develop serum antibody which can block specific T-cell cytotoxic activity of BALB/cfC3H spleen cells; this activity remains detectable throughout life. In addition, recruiting antibody is found in the post-weaning stage. This recruiting activity is apparently directed against the same antigenicity as the blocking activity; it can be detected only rarely in whole serum but is revealed in the 19S fraction when the competing blocking antibodies are sequestered into the 7S fraction. In mid-adult life, 19S recruiting activity is found in only a few of the females; the incidence increases as the females age, and it occurs earlier in those females which subsequently develop mammary tumors. A third antibody activity of serum is blocking factor directed against different MTV-associated tumor-cell-surface antigenicity; this blocks the antibody-dependent cell-mediated cytotoxicity characteristic of spleen cells from BALB/c females horizontally exposed to MTV associated antigenicity. This blocking activity of serum is not found in young females, and in the older females it is more frequent in those which develop mammary tumors. PMID- 6248468 TI - Correlation between perchloric-acid-soluble serum proteins, cellular immunity and tumor-cell burden. PMID- 6248469 TI - Quantification of mouse mammary tumor virus structural proteins in hormone induced mammary tumors of low mammary tumor mouse strains. AB - The expression of the mouse mammary tumor virus (MMTV) in hormone-induced mammary tumors was investigated by means of a radioimmunoassay for two major MMTV proteins, gp52 and p27. MMTV proteins were isolated on lectin affinity- and ion exchange chromatography columns. The purified viral proteins were electrophoretically homogeneous and retained immunoreactivity after labelling with 125iodine. Standard competition assays showed that group-specific antigenic determinants were reacting. Mammary tumors were induced in three strains of mice with a low natural incidence of mammary tumors, C57BL, O20 and C3Hf, by a combined hormone treatment, consisting of hypophyseal isografts and administration of progesterone and estrone. Mammary tumors and mammary glands of hormone-treated animals were extracted and used for competition radioimmunoassays. In general, the tumorigenic hormone treatment resulted in enhanced amounts of MMTV proteins in the mammary glands, compared to the amounts found in lactating mammary glands of untreated animals. The levels of MMTV proteins in the mammary tumors were lower than in the mammary glands. PMID- 6248470 TI - Natural killer cell activity associated with reticulum cell neoplasms. AB - A marked increase in natural killer (NK) activity is observed with lymphoid cells prepared from SJL/J mouse spleen and lymph nodes, in which a transplantable reticulum-cell neoplasm (RCN) is growing. The killer cells are non-adherent, non phagocytic, relatively resistant to X-ray, and scarcely or only partially inactivated by treatment with anti-Thy 1.2 serum and complement. The killer activity is directed against a wide variety of tumor target cells, not requiring homology in histocompatibility, but is selective and not indiscriminate. Kinetics of in vivo development on NK activity, competitive inhibition of in vitro cytotoxicity by target cells and their membrane extracts are described. The NK activity appears to increase in parallel with the infiltration and growth of RCN in these organs. No such augmented NK activity was observed with other types of tumors that grew in these organs of SJL/J mice. (C57BL/6 X SJL/J)F1 mice pretreated with silica to abrogate Hh restriction and subsequently injected with RCN of SJL/J (H-2s) origin supported the growth of transplanted RCN. The high NK activity associated with this RCN was markedly reduced by in vitro treatment with anti-H2b serum plus complement, indicating the host origin of NK cells. However, the close association of RCN growth with elevated NK activity may indicate a special function of RCN in promoting NK activity by an unknown mechanism(s) of cellular interactions. PMID- 6248471 TI - Cyclic nucleotides and prostaglandins in psoriasis. AB - The changes in cAMP, cGMP, adenylate cyclase, cyclic phosphodiesterase, and prostaglandins in psoriatic epidermal cells were compiled and critically discussed. The results of the pertinent studies permit the assumption that therapeutic approaches in psoriasis via the system of cyclic nucleotides and prostaglandins might be promising. PMID- 6248472 TI - Immunological alterations in psoriasis. PMID- 6248473 TI - Exocrine gland enzyme levels after peroral administration of xylitol and sorbitol in the rat. AB - Rats were given xylitol or sorbitol perorally during a 150-day period in drinking water. The polyols were given in equimolar concentrations and their average daily consumption was 2.0 g per kg body weight. At the end of the feeding schedule the submandibular, parotid and lacrimal glands of the animals were studied for the levels of peroxidase, alpha-amylase, proteases and protein. The sorbitol-fed rats had lower body weights compared with the xylitol-fed siblings, but the differences were not significant. The same concerned the fresh weights of the glands studied. The levels of the enzymes and protein determined did not differ significantly between the feeding groups. The results provided further support to the idea that sorbitol and xylitol may not differ with regard to their effects on the peroxidase, amylase and proteinase levels of the three exocrine glands studied in rats, and that the xylitol-associated increase of the lactoperoxidase levels, previously observed with saliva, may confine to primates only. PMID- 6248474 TI - The effect of food deprivation on the activities of some enzymes of the metabolism of carbohydrates in the submandibular salivary glands of rats. AB - Male albino rats of the Wistar strain were deprived of food, but not water, and killed at various periods. Enzymes of the metabolism of carbohydrates were assayed in the submandibular salivary glands after 24, 48, 72, 96 and 120 hours of starvation. The body weight loss was accompanied by a decrease in gland weight and gland protein content. Blood glucose fells to about 70% the control level. Hexokinase showed no variation with increasing periods of food deprivation. The decrease in the activity of phosphofructokinase was greater than that one observed for glucose-6-phosphate dehydrogenase, indicating a shift in glucose utilization by the cells, from the glycolytic to the pentose phosphate pathway. PMID- 6248475 TI - Vitamins and alcoholism. II. folate and vitamin B12. PMID- 6248476 TI - Functional correlates of anterior pituitary cytology. PMID- 6248477 TI - Ovarian follicular and luteal physiology. AB - Follicular maturation and development is a complex process of interrelated intra- and extraovarian events that ultimately lead to ovulation of a mature oocyte and transformation of the ruptured follicle into a corpus luteum. The primordial follicle consists of an immature oocyte arrested in the dictyate stage of meiosis, surrounded by a single layer of relatively undifferentiated granulosa cells. The oocyte remains in the immature state because of many factors, one of which is the oocyte maturation inhibitor (OMI) secreted by granulosa cells. The oocyte subsequently increases in size, and as the antrum forms it becomes surrounded by cumulus cells. The cumulus cells may be intimately involved in the action of O,I to arrest the oocyte in the immature state within the follicle, as well as the resumption of meiosis during the LH surge. The compartments of the follicle that change most dramatically during follicular maturation are the cells lining the follicle--the granulosa and thecal cells. Under the influence of estrogen and FSH, the granulosa cells proliferate and also acquire FSH receptors. At this time, the thecal compartment differentiates and surrounds the granulosa cells, but remains separated from them by a basement membrane. Steroid secretion by the antral follicle involves the interplay of androgens, estrogens, and progestins. Both the granulosa and thecal cell compartments contribute to follicular fluid and serum levels of steroids; the interaction of both cell types may be necessary for estrogen and progesterone secretion in some species. As a consequence of the presence of an elevated number of FSH receptors, the granulosa cells of the small antral follicle are able to respond to FSH in many ways, including increased cyclic AMP accumulation, activation of the aromatase system, and induction of LH receptors, which permits the granulosa cells to later respond to LH. The mechanism by which thecal cells acquire their LH receptors is presently unknown. The granulosa cells of the follicle may indirectly control their own maturation and the number of follicles maturing through the secretion of follicular inhibin, which decreases the pituitary output of FSH. Even though the granulosa cells have acquired large numbers of LH receptors, they are prevented from luteinizing prematurely by factors in follicular fluid, including estrogen and a luteinizing inhibitor (LI). As serum LH levels increase during the preovulatory LH surge, a number of events occur: resumption of oocyte meiosis, transformation of the steroid enzyme complex from estrogen to progesterone secretion, follicular rupture, and formation of the corpus luteum. Granulosa cells form the bulk of the corpus luteum, which secretes elevated amounts of progesterone for a fixed time period depending on the species. Before ovulation the preovulatory follicle must be exposed to and respond to adequate LH and FSH levels in order for the eventual corpus luteum to secrete elevated amounts of progesterone for its normal lifespan... PMID- 6248478 TI - Endocrinology of late pregnancy and parturition. PMID- 6248479 TI - Regulation of testicular function: a spatial and temporal view. PMID- 6248480 TI - Structural aspects of brain barriers, with special reference to the permeability of the cerebral endothelium and choroidal epithelium. PMID- 6248482 TI - Enzyme-linked immunosorbent assay for detection of virus-specific IgM antibodies to varicella-zoster virus. AB - A sensitive enzyme-linked immunosorbent assay (ELISA) is described for detection of varicella-zoster virus (VZV) IgM antibodies. The antigen consisted of a sonically disrupted extract of VZV-infected human embryo cells. The tested sera were absorbed with Staphylococcus aureus (strain Cowan I) before analysis. Rabbit anti-human IgM peroxidase conjugate was used to detect human IgM bound to viral antigen. The results were compared with those obtained by the indirect fluorescent antibody to membrane antigen (IFAMA) technique. Comparison of titers obtained by ELISA with those obtained by IFAMA for sera of chickenpox patients showed agreement between the results in 8 of 9 patients. In 1 chickenpox patient, no VZV IgM antibodies could be detected by IFAMA, while a titer of 3,200 was obtained by ELISA. The ELISA technique described gave titers more than 100 times higher than those obtained by IFAMA. VZV IgM antibody was detected by ELISA and IFAMA in only 1 of 5 zoster patients. No VZV IgM antibodies were found by ELISA in 45 control sera (healthy adults and hospitalized patients with various other diseases). Neither were they found in paired sera of 6 patients with acute herpes simplex infections, 2 patients with Epstein-Barr virus infections, and 3 patients with human cytomegalovirus infections. PMID- 6248483 TI - Analysis of the transformation of human lymphocytes by Epstein-Barr virus. II. Abortive response of leukemic cells to the transforming virus. AB - Leukemic lymphocytes with B-cell markers were obtained from the peripheral blood of 4 patients with chronic lymphocytic leukemia (CLL) or acute lymphocytic leukemia (ALL); a significant number of T cells was not involved. The lymphocytes were inoculated with the transforming B95-8 Epstein-Barr virus (EBV). Synthesis of EBV-determined nuclear antigen (EBNA) occurred in three CLL preparations: 15.1 -25.4% of cells expressed maximum EBNA 24--48 h after viral exposure. A characteristic immunofluorescence pattern similar to a coarsely clumped chromatin structure was observed. In contrast to EBV infection of normal lymphocytes, EBNA synthesis in CLL cells (morphologically similar to normal lymphocytes) was not followed by either blastogenesis or DNA synthesis. EBNA-positive cells, which usually degenerate within 1--2 weeks, could be maintained for more than 30 days on feeder human embryo fibroblasts pretreated with mitomycin C. DNA synthesis and mitosis occurred, but unlimited cell growth did not. 41.9% of ALL cells were EBNA positive at 36 h prior to DNA synthesis, and they subsequently grew rapidly for up to 9 days. The cell proliferation, however, was temporary, and death resulted in about 2 weeks. No significant synthesis of EBV-related early antigens and viral capsid antigen was noted in any of the infected cultures throughout the incubation period. These results indicate that certain intracellular restrictions may have exceeded the potent transforming capacity of EBV in these target leukemic cells. PMID- 6248481 TI - Restriction of C-type viral antigen in H-2/Fv-1 syngeneic mouse somatic cell hybrids. AB - Somatic cell hybrids between an AKR lymphoma or a C3H sarcoma and H-2, Fv-1 syngeneic CBA sarcoma or carcinoma have been examined for expression of the structural components of murine leukemia virus (MuLV) by radioimmunoassay and complement-dependent cytotoxicity assay. Parental AKR and C3H cells contained high concentrations of MuLV core protein p30 in their cell extracts and showed high sensitivity to anti-MuLVgp70 and p30 sera. In contrast, CBA cells expressed little detectable p30 in the extracts, were much less sensitive to anti-gp70 serum, and were almost insensitive to anti-p30 serum. The hybrids between the AKR or C3H cells and CBA cells had a decreased amount of p30 in the extracts and were almost resistant to cytotoxicity by anti-p30 serum, although they maintained high sensitivity to anti-gp70 serum. These findings suggest that the CBA genotype suppresses the production and cell-surface expression of p30 antigen of AKR and C3H endogenous C-type viruses. The suppressive gene is not Fv-1n. PMID- 6248484 TI - Tandem integration of avian retroviruses in double-infected cells. AB - Chicken embryo fibroblasts were chronically infected by both RAV-1 and SR-E, and established SR-E-transformed quail cells were superinfected with RAV-1. About 75 and 50% of double-infected and superinfected cells, respectively, produced both parental viruses. The DNA purified from these cells contained infectious provirus of both parents and no detectable recombinant provirus. In assays using agar overlay, about 5% of the transformed foci that were induced by the DNA of double infected, but not superinfected, cells were found to contain the progeny of both parents. This observation suggests that in double infections with avian retroviruses, DNA of both parent viruses may integrate into the host genome either in tandem or in close proximity. PMID- 6248485 TI - Rotavirus in Buenos Aires, Argentina. AB - Rotavirus was studied over a 1-year period in 141 hospitalized children suffering from gastroenteritis and in 120 control children. Electron microscopy and discontinuous counterimmunoelectrophoresis techniques were employed with equal success. Rotavirus was detected with high frequency in children suffering from diarrhea (45 cases; 32%) and in only 2 cases (1.6%) of the control group. A marked seasonal distribution, with 80% in July (winter) and a decrease (0%) in December (summer), was observed. The frequency of infection with rotavirus was highest in infants between 0 and 6 months of age. Seroconversion, studied by complement fixation, was obtained in 34 of 42 (80%) virus-positive children, and antibody without conversion was observed in 8 (19%). Of 58 virus-negative children, 51 (96.2%) were negative for antibody and only 2 (3.7%) developed antibody. PMID- 6248486 TI - [Isolation of virus-like particles in Heck's focal epithelial hyperplasia]. AB - Report of the isolation of virus-like particles with the morphology of the papilloma-virus-group in a case of focal epithelial hyperplasia Heck. PMID- 6248487 TI - Radon in dwellings and lung cancer-a discussion. PMID- 6248488 TI - The pathology of head and neck tumors: squamous and mucous-gland carcinomas of the nasal cavity, paranasal sinuses, and larynx, part 6. AB - Carcinomas of the nasal cavity and paranasal sinuses are statistically dominated by squamous-cell lesions, which account for between 85% and 90% of the epithelial malignancies in these sites. Neoplasms of glandular derivation are far less frequent, accounting for between 4% and 8% of carcinomas in this region. Both classes of malignancy, however, indicate an ominous prognosis for their hosts, and for both, it is the extent of the cancer, and hence the clinical stage, that is the major determinant. The clinicopathologic characteristics of squamous-cell and glandular carcinomas of the nasal cavity and paranasal sinuses are presented, and for the latter, a review of their presentation in the larynx is also offered. PMID- 6248489 TI - Biosynthetic evidence for instability of HB M Saskatoon. PMID- 6248490 TI - Action of restriction endonucleases on the DNA and chromosomes of Muntiacus muntjak. PMID- 6248491 TI - X-ray microanalysis of colloidal-gold-labelled lysosomes in rat liver sinusoidal cells after incubation for acid phosphatase activity. AB - The lysosomal apparatus of the Kupffer and endothelial cells of the sinusoidal lining of the rat liver was found to take up colloidal-gold particles with a mean diameter of 5 nm, prepared according to a modified method. After incubation of the glutaraldehyde-perfusion-fixed tissue in a lead-containing medium for the demonstration of acid phosphatase activity, a reaction product was observed in the gold-loaded lysosomes. By X-ray microanalysis of such lysosomes, the presence of osmium, gold and lead was detected qualitatively in the unstained sections from the tissue, which after the incubation had been post-fixed with an OsO4 solution to which K4Fe(CN)6 had been added to enhance the contrast. The quantitative computer-assisted processing of the X-ray microanalytical data from such lysosomes enabled to determine the gold-to-lead ratio and the individual gold and lead peak intensities derived from both the M chi and L chi values in the spectra. On the basis of these results and those obtained similarly in control lysosomes containing either only gold or only lead phosphate precipitate, it was found that only the L chi values were reliable, whereas the M chi values from the same lysosomal spectra were unrealistic, due to deconvolution problems in the computer programs applied. Based upon the L chi values it was found that among the population of lysosomes in single Kupffer cells, studied after a 60-min interval between the injection of the gold colloid and fixation, three types of lysosomal contents could be quantitated by X-ray microanalysis, viz. one type with only gold, one with only lead, one with gold and lead, in various ratios. This quantitative approach might make it possible to detect variations in lysosomal composition associated with ageing. PMID- 6248492 TI - Ultracytochemistry of cyclic 3',5'-nucleotide phosphodiesterase activity in the planarian Dugesia lugubris (O. Schmidt). AB - The enzyme 3',5'-nucleotide phosphodiesterase was localized in certain tissues of the planarian Dugesia lugubris (O. Schmidt) by means of ultracytochemical methods. This enzyme was found to be active in epithelium, muscles, nerve tissue and in rhabdite-forming cells. The active enzyme was present at the outer or inner side of the membrane, and even in the cytoplasm. Problems of the ultracytochemical localization of PDE are discussed. PMID- 6248493 TI - Bilateral Wilm's tumor. PMID- 6248494 TI - Extrinsic compression of superior vena cava an analysis of 41 patients. PMID- 6248495 TI - Fast neutrons compared with megavoltage x-rays in the treatment of patients with supratentorial glioblastoma: a controlled pilot study. PMID- 6248497 TI - Fast neutron therapy for advanced brain tumors. PMID- 6248496 TI - Experience with neutron therapy for locally advanced sarcomas. PMID- 6248498 TI - Radioprotection of the rat parotid gland by WR-2721: morphology at 60 days post irradiation. PMID- 6248500 TI - The degradation rates of type I, II, and III collagens by tadpole collagenase. AB - The degradation rates of type I, II, and III collagens by tadpole collagenase were studied by measuring the viscosity of the solution and the contents of alpha chains and alpha A chains of collagen, using SDS-polyacrylamide gel electrophoresis followed by densitometric analysis of the separated peptide bands. An empirical parameter was derived from the viscosity, and was shown to change in parallel with the content of alpha chains upon incubation with tadpole collagenase almost to the stage of complete digestion of collagen. Linear plots of parameters reflecting the concentration of intact collagen molecules against time were obtained, indicating the degradation to be pseudo-first order. The first-order rate constants for the degradation of Type I, II, and III collagens with tadpole collagenase at 30, 25, and 20 degrees C gave activation energies of 60 kcal/mol for Type III collagen and 40 kcal/mol for Type I and II collagens. There appeared to be a dependency of the degradation rates on the conformation of the collagen molecules (which is affected by temperature). PMID- 6248499 TI - The existing forms of collagenase in the human uterine cervix. AB - The existing forms of collagenase [EC 3.4.24.7] in the human uterine cervix were examined. The latent collagenase extracted by homogenization in 0.25% Triton X 100 containing 0.01 M CaCl2 was indicated to be a complex of collagenase with alpha 2-macroglobulin by the behavior of the fraction of this enzyme before and after treatment with NaSCN on Sephadex G-150 column chromatography and an immunodiffusion method. The active collagenase was extracted by rehomogenization in 50 mM Tris-HCl buffer, pH 7.4, containing 0.1 M M CaCl2 from the insoluble residue at 0 degrees C. Another latent collagenase was extracted from the insoluble fraction in the same buffer by heating at 60 degrees C for 4 min and this enzyme was activated by 4-aminophenylmercuric acetate or trypsin. The molecular weights of the active and the latent forms were approximately 7.3 x 10(4) and 9.4 x 10(4), respectively. This indicates that the latency is due to the formation of a low molecular weight inhibitor enzyme complex. These results clarified that the human uterine cervix contains three existing forms (alpha 2 macroglobulin complex, active form and low molecular weight inhibitor complex) of collagenase under these experimental conditions. PMID- 6248501 TI - Degradation rates of type II and III collagens by tadpole collagenase are modulated by mutual presence. AB - Degradation of type II and III collagens by tadpole collagenase in a mixture of both substrates was monitored by SDS-polyacrylamide gel electrophoresis in 3 M urea, followed by densitometric quantiation. The degradation rates of type II and III collagens were increased and decreased, respectively, by the mutual prsence, compared with those of type II and III collagens alone. The results suggest that the degradation of type II collagen in vivo may be regulated by the presence of other type(s) of collagen, particularly in such a case as resorption of cartilage in the region of newly forming osteoid tissue. PMID- 6248502 TI - Interaction between SV40 DNA and camptothecin, an antitumor alkaloid. AB - Camptothecin specifically interacted with closed superhelical circular SV40 DNA during incubation in 1.0 M NaCl at 37 degrees C and induced an alkali-labile linkage in the E strand. No interaction occurred in the reaction mixture containing 0.1 M NaCl, or at 4 degrees C. As camptothecin did not affect linear SV40 DNA, the superhelical structure of DNA appeared to be essential. The site of the alkali-labile linkage induced in SV40 DNA I through interaction with camptothecin was near the origin of replication on the basis of the results of experiments with restriction enzymes. Neither sulfhydryl reagents nor EDTA affected the interaction between camptothecin and SV40 DNA I, so the action of camptothecin is different from those of antitumor antibiotics, bleomycin or neocarzinostatin. Analysis of the s20,0w value of SV40 DNA I after the interaction with camptothecin and the sedimentation profiles of DNA after heating in the reaction mixture indicated that the interaction between camptothecin and SV40 DNA I was different from those of intercalating or alkylating agents such as ethidium bromide and methylmethanesulfonate. Replacement of the OH group at C-20 in the E ring of camptothecin by H-, CH3-, and Cl- resulted in the reduction, in this order, of the potency for interaction with SV40 DNA I to induce an alkali labile linkage. PMID- 6248503 TI - Purification and properties of deoxyribonuclease II from human urine. AB - The acid deoxyribonucleases [DNase II; EC 3.1.4.6] in human urine were purified approximately 400- to 500-fold by phosphocellulose chromatography, gel filtration on Sephadex G-75 and isoelectric focusing, with a total recovery of 22%. The enzymes were present in a least three forms with different isoelectric points, pHs 6.4, 6.6, and 6.8. However, other properties were essentially similar. The enzymes did not require divalent cations for activity, and the optimal pHs were at 5.1 to 5.3 in 33 mM acetate buffer. They had a molecular weight of around 36,000, as estimated by gel filtration on Sephadex G-75. The enzymes were endonucleases which hydrolyzed native, double-stranded DNA about 5 to 15 times faster than thermally denatured DNA. The products formed from native DNA were 3' phosphoryl- and 5'-hydroxy-terminated oligonucleotides. The average chain length of the limit digests with these enzymes was approximately 11 to 15, and the major fragments were longer than pentanucleotides. The final preparations were free of nonspecific acid and alkaline phosphatases and phosphodiesterase, but contained contaminating ribonuclease activity. PMID- 6248504 TI - Components of the cytochrome system of Alcaligenes sp. N.C.I.B., 11015, with special reference to particulate bound c-type cytochromes. AB - 1. The cytochrome type of the particulate fraction from cells of Alcaligenes sp. was examined. The particulate fraction of aerobically-grown cells contained b-, c , a-type and o-type like cytochromes, whereas that from nitrate-grown cells contained b-, c-type and o-type like cytochromes. 2. Two kinds of c-type cytochromes were extracted and purified from the particulate fraction of nitrate grown cells of Alcaligenes sp. One of them showed absorption maxima at 415.5, 522, and 551 nm is the reduced form, and at 410.5 nm in the oxidized form; the other at 417.5, 523, and 556 nm in the reduced form, and at 412 nm in the oxidized form; these cytochromes were designated cytochrome c-551 and cytochrome c-556, respectively. 3. Cytochrome c-551 had a molecular weight of 28,800 and had two heme groups per molcule. The midpoint oxidation reduction potential at pH 7.0 (Em, 7) was +262 mV. Cytochrome c-556 had a molecular weight of 18,200 and contained one heme group per molecule. The Em, 7 value was +291 mV. These cytochromes were not autoxidizable, did not react with carbon monoxide or KCN at pH 7.0, and were reduced by ascorbate. 4. Each cytochrome acts to some degree as electron carrier in the dissimilatory nitrite reduction reaction of Alcaligenes sp. PMID- 6248505 TI - Effect of reducing agents on the solubilization of renal sodium and potassium dependent ATPase with detergent. AB - A high concentration (0.5 M) of a reducing agent such as dithiothreitol or 2 mercaptoethanol inactivated both crude (microsomal) and purified preparations of Na+,K+-ATPase only in the presence of detergent. The concentration of SDS needed for inactivation by a reducing agent was low (around 0.3 mg/ml), and was similar to that required for activation in the absence of reduction. The subunits of the enzyme after inactivation with a reducing agent were not sedimented by centrifugation at 100,000 x g for 1 h. Electron microscopic observation of the inactivated enzyme revealed that membranous structures were dominant in the pellet obtained by centrifugation, whereas many particles were present in the supernatant. These results suggest that Na+,K+-ATPase was inactivated by reduction of disulfide bond(s) embedded within the lipid bilayer in the presence of detergent, and that the subunits of the resulting enzyme were no longer bound to the membrane. PMID- 6248506 TI - Autoreduction of spinach plastocyanin at alkaline pH. AB - The autoreduction of spinach plastocyanin has been studied by fluorescence, absorption, and paramagnetic resonance spectroscopy. Decolorization of oxidized plastocyanin, due to the autoreduction of plastocyanin, occurred rapidly at alkaline pH (half-life 20 min at pH 10.2). Its rate also increased with increasing ionic strength. In the presence of a hydrophobic fluorescent probe such as 2-p-toluidino-naphthalene-6-sulfonate (TNS), the fluorescence intensity of TNS due to binding to oxidized plastocyanin gradually increased following the autoreduction of plastocyanin, which suggests that copper is autoreduced in parallel with the exposure of a hydrophobic site (probably near Cys 84) to the solvent. The EPR spectra also supported the change of coordination geometry of copper. The reduction rate of plastocyanin by ferrocyanide at alkaline pH was almost the same as that at neutral pH, and TNS did not alter the exogenous reduction rate even at alkaline pH. These results suggest that exogenous and endogenous reduction take place independently at different reduction sites in spinach plastocyanin. PMID- 6248507 TI - Assay of repair enzyme activity by reactivation of ultraviolet-irradiated infective viral DNA. PMID- 6248508 TI - Effects of surface potential on the equilibrium and kinetics of redox reactions of membrane components with external reagents in chromatophores from Rhodopseudomonas sphaeroides. AB - The characteristics of the salt and pH dependences of the redox levels of cytochrome c2 and reaction center bacteriochlorophyll were studied in chromatophores from Rhodopseudomonas sphaeroides. They could be explained in terms of the difference of redox potential in the membrane from that in the bulk aqueous phase due to the electrostatic potential difference arising from charges fixed on the membrane surface. The midpoint potentials (Em) became lower when the surface potential (the electrostatic potential at the surface with reference to the bulk aqueous phase) had large negative values at lower salt concentrations at neutral pH, as predicted by the Gouy-Chapman theory. The rate of oxidation of cytochrome c2 in chromatophores by ferricyanide also depended on salt and pH levels. The rate was low at low salt concentrations, probably because of the lower surface concentration of ferricyanide compared with the bulk concentration, due to the surface potential. PMID- 6248509 TI - Comparative studies on alveolar macrophages and polymorphonuclear leukocytes. I. H2O2 and O2- generation by rabbit alveolar macrophages. AB - The oxidative metabolism of rabbit alveolar macrophages (A-MO) was compared with that of rabbit polymorphonuclear leukocytes (PMN) with respect to H2O2 generation by intact cells or subcellular fractions. Rabbit PMN exhibited an increase in the oxygen uptake and a marked release of H2O2 upon addition of heat-killed E. coli in the presence and absence of opsonin. However, rabbit A-MO exhibited an increase in the oxygen uptake upon addition of E. coli only in the presence of anti-E. coli serum as an opsonin, whereas a very small amount of H2O2 release was observed during ingestion of the opsonized E. coli. The generation of O2- and H2O2 by a granule-rich fraction isolated from phagocytosing PMN was larger than that by a similar fraction isolated from resting PMN. However, there was no significant difference in O2- and H2O2 generation by the granule fractions between phagocytosing and resting A-MO in the presence of either NADH or NADPH. In contrast to the granule fraction of rabbit PMN, the O2- and H2O2 generating activities in the A-MO granule fraction were higher in the presence of NADH than in the presence of NADPH. The rates of NADH and NADPH oxidation by both A-MO and PMN granule fractions were measured with and without addition of Mn2+ to the assay medium. The effect of Mn2+ on the NAD(P)H oxidase was found to differ between rabbit A-MO and PMN. PMID- 6248510 TI - Identification of 2':3'-cyclic nucleotide 3'-phosphodiesterase in the vertebrate retina. AB - The enzyme, 2':3'-cyclic nucleotide 3'-phosphodiesterase (2':3'-cNMP-3'-ase) has been used as a marker in the nervous system for the presence of myelin membrane or myelin-producing glial cells. In this study, goldfish and bovine neural retinas are found to have high levels of such a diesterase activity. Analysis of retinal tissue incubated with 2':3'-cAMP shows only 2'-AMP as the reaction product, indicating the selective hydrolysis of the cyclic nucleotide. Microdissection of the goldfish retina demonstrates the highest 2':3'-cNMP-3'-ase activity in the region of the photoreceptors. A fraction enriched in bovine rod outer segments has about a 5-fold increase in specific enzyme activity when compared to whole retina preparations. These data suggest that 2':3'-cNMP-3'-ase is either closely associated with or is an intrinsic feature of vertebrate photoreceptor elements. The retina, which contains this enzyme, may serve as a model to investigate the influence of 2':3'-cyclic nucleotides on a function of the nervous system. PMID- 6248511 TI - Retinoic acid increases cyclic AMP-dependent protein kinase activity in murine melanoma cells. AB - The influence of all trans-retinoic acid on cyclic AMP metabolism was examined in B16-F1 mouse melanoma cells. Treatment of these cells with retinoic acid resulted in a dose-dependent inhibition of cell growth which was accompanied by a concentration-dependent increase in both basal and cyclic AMP-stimulated protein kinase activity, Intracellular levels of cyclic AMP, however, were not altered by retinoid treatment. A protein kinase-deficient variant of B16-F1 (MR-4) did not exhibit decreased growth or increased protein kinase activity in response to retinoic acid treatment. At least 24 h of incubation was required before increased protein kinase activity could be detected in treated B16-F1 cells. Retinoic acid treatment increased the Vmax of protein kinase, but the Ka for cyclic AMP activation was not altered. These findings suggest that in B16 mouse melanoma cells, cyclic AMP-dependent protein kinase may be a target for the growth inhibitory effects of the retinoid. PMID- 6248512 TI - Assembly of the mitochondrial membrane system. Sequence of the oxi 2 gene of yeast mitochondrial DNA. AB - The region of mitochondrial DNA (mtDNA) containing the oxi 2 locus has been sequenced in a rho- clone (DS40) derived from the respiratory competent strain D273-10B/A48 of Saccharomyces cerevisiae. The DS40 clone was established to have retained only genetic markers in the oxi 2 locus and to have a segment of mtDNA extending from 18.6 to 24.3 units of the wild type map. The mitochondrial genome of DS40 includes a sequence that has been tentatively identified as the structural gene of Subunit 3 of cytochrome oxidase. The coding sequence is 810 nucleotides long and generates a protein with a molecular weight of 30,340. The amino acid composition of the oxi 2 gene product deduced from the nucleotide sequence is in agreement with the composition of the purified Subunit 3 of yeast cytochrome oxidase. The orientation of the DS40 mtDNA segment relative to wild type mtDNA indicates that the oxi 2 gene is transcribed from the same DNA strand as the oxi 1 and several other mitochondrial genes. PMID- 6248513 TI - Bovine thymus poly(adenosine diphosphate ribose) polymerase. Physical properties and binding to DNA. AB - Purified bovine thymus poly(adenosine diphosphate ribose) polymerase is a monomeric protein with a single polypeptide chain having a molecular weight of approximately 130,000, determined by sodium dodecyl sulfate-gel electrophoresis, analytical ultracentrifugation, and gel filtration. A high frictional ratio (1.81) indicated that the molecule has an elongated shape, or a high solvation, or both. The enzyme is a basic protein (pI 9.8), and amino acid analysis showed a relatively high lysine content. The enzyme activity is dependent on double stranded DNA and is solely correlated with single- or double-stranded breaks on the DNA. Filter binding assay technique showed that the enzyme-activating efficiency of DNA correlated sufficiently with its enzyme-binding efficiency. Thus, a very high enzyme-activating efficiency of a DNA fraction (active DNA) which was separated from the crude enzyme fraction is mainly due to its high enzyme-binding efficiency. It was also shown that single-stranded DNA and heparin had a strong inhibitory effect on the binding of the enzyme to double-stranded DNA, whereas competitive inhibitors did not affect the binding, We interpret these results to indicate that the binding of the enzyme to double-stranded DNA is a prerequisite step to its catalytic activity and has a dual function: (a) to position the enzyme on specific binding sites such as single- or double-stranded breaks on the DNA, and (b) to induce an active conformation of the enzyme. PMID- 6248514 TI - Low temperature kinetic studies on rat liver mitochondria containing covalently linked derivatives of cytochrome c. PMID- 6248515 TI - The binding of cytochrome c peroxidase and ferricytochrome c. A spectrophotometric determination of the equilibrium association constant as a function of ionic strength. AB - Complex formation between cytochrome c peroxidase and ferricytochrome c perturbs the optical absorption spectrum in the Soret band by about 2%. This perturbation can be utilized as a measure of the complex formed in solution and permits the determination of the stoichiometry and the equilibrium association constant for this reaction. At pH 6, in cacodylate/KNO3 buffers, only a 1:1 complex between cytochrome c peroxidase and ferricytochrome c is detected. The equilibrium association constant for the complex has been determined as a function of ionic strength and varies between (6.0 +/- 3.6) x 10(6) M-1 and (2.2 +/- 1.9) x 10(6) M 1 over the ionic strength range 0.01 M to 0.20 M. PMID- 6248516 TI - Stoichiometry and molecular weight of the minimum asymmetric unit of canine renal sodium and potassium ion-activated adenosine triphosphatase. AB - Sodium and potassium ion-activated adenosine triphosphatase is known to be composed of at least two different polypeptides, alpha and beta. When a detergent treated supernatant preparation of the enzyme is reacted with the cross-linking reagent, cupric phenanthroline, a single, covalent heterodimer is formed. This product is formed from one of each of the two polypeptides. The remaining, unreacted alpha and beta chains maintain a constant ratio to each other throughout the reaction. The same heterodimer is formed in membrane-bound enzyme when reacted with several other cross-linking reagents. The protein mass ratio between the chains in the native enzyme, determined by two methods, is 2.15 +/- 0.16. Using this value and a value of 121,000 +/- 6,000 for the molecular weight of the larger polypeptide, a molecular weight of 56,000 +/- 7,000 can be calculated for the protein portion of the smaller polypeptide. Upon removal of a substantial portion of the carbohydrate from the smaller polypeptide, a change in its electrophoretic mobility is observed, while that of the larger polypeptide remains unaffected. The apparent length of this unglycosylated small chain is 450 residues, corresponding to a molecular weight of 51,000. Taken together, these results demonstrated that the two polypeptides of the (Na+ + K+)-ATPase exist in an equimolar, noncovalent association in the native enzyme, and that the protein molecular weight of the minimum asymmetric unit is 177,000 +/- 13,000, Previous results which address the question of the quaternary structure of the ATPase are re-examined in light of these determinations. PMID- 6248517 TI - On the mechanism of action of adrenocorticotropic hormone. The role of ACTH stimulated phosphorylation and dephosphorylation of adrenal proteins. AB - The regulatory role of phosphorylation of adrenal proteins as it relates to the mechanism of action of adrenocorticotropic hormone (ACTH) has been studied. ACTH, cyclic AMP, or cyclic GMP were added to rat adrenal quarters which had been preincubated with [32P]phosphate. 32P-labeled proteins in subcellular fractions were identified after separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. The addition of ACTH consistently resulted in the phosphorylation and dephosphorylation of specific adrenal proteins and produced characteristic phosphorylation patterns (autoradiographs) for each subcellular fraction which were very different from control. The changes in phosphorylation of proteins preceded corticosterone production. Also, the degree of phosphorylation of these specific proteins followed a dose-response relationship with ACTH which correlated well to the dose-response for corticosterone production. When cAMP was added to adrenal quarters, the resulting phosphorylation changes were identical to those induced by ACTH. When cGMP was added to adrenal quarters, the resulting phosphorylation patterns were very similar to those produced by control incubations. ACTH or cAMP stimulated corticosterone production 6-fold when compared to control or cGMP-treated tissue. These results suggest that tropic action of ACTH is mediated by cAMP by both phosphorylation and dephosphorylation of specific adrenal proteins. PMID- 6248518 TI - The intrinsic ATPase of DNA gyrase. PMID- 6248519 TI - The isolation of the beta A-, beta C-, and gamma-globin genes and a presumptive embryonic globin gene from a goat DNA recombinant library. AB - As an approach to understand how the expression of globin genes are regulated during development, clones containing globin DNA sequences were selected from a recombinant library of goat genomic DNA. The type of globin gene present in each of the recombinants was determined by cross-hybridization to the DNA of mouse alpha- and beta-globin cDNA-containing plasmids. Of 11 clones isolated, eight hybridized specifically to the DNA of the mouse beta-globin plasmid, while one clone hybridized only to the DNA of the alpha globin plasmid. The location of each globin sequence within its DNA insert was determined by a combination of restriction enzyme mapping and Southern transfer-hybridizations. Selected fragments were sequenced; comparisons of the amino acids coded for by these regions with those of the goat globins identified clones carrying beta A-, beta C , and gamma-globin genes. Another recombinant coded for amino acid sequences resembling, but not identical with, the known goat globins, and was identified tentatively as containing an embryonic or epsilon-gene. Detailed analysis of the clone containing the beta C gene and an overlapping clone revealed that three other beta-like sequences are located 6, 12, and 21 kilobases on the 5'-side of the beta C gene. The globin sequence of the locus nearest to the beta C gene has an altered translation termination codon and, if transcribed and translated, would give a globin chain seven amino acids longer than the normal goat beta C globin. In addition, the sequence following this termination codon is very AT rich, unlike that of other globin genes. The recombinants described contain extensive regions of DNA surrounding the globin genes, making them useful for identifying regulatory sequences as well as determining the sequence organization of the goat globin genes. PMID- 6248520 TI - Glycopeptides from brain inhibit rates of polypeptide chain elongation. AB - In previous reports, we have identified cell-surface glycopeptides from mouse cerebrum (BCSG) that inhibited protein synthesis and mitosis in several cell types. When baby hamster kidney (BHK)-21 cells were infected with vesicular stomatitis virus (a negative strand RNA virus), BCSG extensively inhibited viral protein synthesis. This inhibition was effective against both protein and glycoprotein synthesis and was independent of amino acid uptake by infected cells, synthesis of viral RNA, and degradation of viral proteins. Analysis of polyribosome profiles in uninfected BHK-21 cells indicated that the degree of cellular protein synthesis inhibition could not be attributed to activation of RNase or solely to a disruption of chain initiation. When added directly to a cell-free protein-synthesizing system derived from BHK-21 cells, BCSG was ineffective, but if the inhibitory material was first allowed to react with cells, cell-free protein synthesis was substantially reduced. When BCSG were reacted with cells for 5 min at 0 degrees C, the cells tested, BHK-21 (a BCSG sensitive line) and murine fibrosarcoma 2237 (a BCSG-insensitive line), both effectively adsorbed the inhibitor from the medium. PMID- 6248521 TI - Compartmentation of glycolytic enzymes in nerve endings as determined by glutaraldehyde fixation. AB - Considerable amounts of five glycolytic enzymes glucosephosphate isomerase, glyceraldehyde-phosphate dehydrogenase, aldolase, pyruvate kinase, and lactate dehydrogenase, became fixed when intact synaptosomes were incubated with glutaraldehyde. Other glycolytic enzymes were immobilized much less by this procedure. The lactate dehydrogenase isoenzymes showed a variable response to glutaraldehyde fixation. The isoenzymes enriched in muscle subunits were rapidly immobilized by glutaraldehyde, while the isoenzymes enriched in heart subunits, especially H4, were not. It is suggested that the enzymes which were immobilized are located near the synaptosomal membrane, perhaps in association with actin, which is found at this site. The enzymes that showed a much smaller degree of fixation were either randomly distributed in the synaptoplasm or less susceptible to fixation. PMID- 6248522 TI - Isolation and characterization of two proteins possessing Hpa II methylase activity. AB - Two proteins exhibiting Hpa II methylase activity have been purified to homogeneity from Haemophilus parainfluenzae and their physical and catalytic properties have been studied. Separation of the two Hpa II methylase activities was achieved by DEAE-Sephadex A-50 chromatography. In subsequent steps, each methylase was purified separately by chromatography on Sephacryl S-200, phosphocellulose, and hydroxylapatite. The proteins have molecular weights of 38,500 +/- 1,000 (Hpa II) and 41,500 +/- 1,000 (Hpa II') as judged by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Sedimentation equilibrium analyses of the native proteins yield molecular weights of 38,800 +/- 3,000 and 42,200 +/- 3,000 for Hpa II and Hpa II', respectively, indicating that both enzymes are composed of a single subunit. Furthermore, both methylases exhibit identical specificity in the methylation of the nucleotide sequence dC-C-G-G in simian virus 40 (SV40) DNA and in a short synthetic oligonucleotide duplex. Although pH, temperature, and salt optima are the same for both enzymes, homogeneous Hpa II' methylase is more stable than Hpa II methylase. Preliminary peptide mapping indicates that the two enzymes are structurally related, suggesting the possibility that Hpa II' methylase may represent a precursor form of Hpa II methylase. PMID- 6248523 TI - A single-stranded nucleic acid-binding protein from Artemia salina. I. Purification and characterization. AB - A protein that binds tightly to single-stranded but not to double-strained nucleic acids has been purified to homogeneity from a high salt wash of ribosomes from cryptobiotic Artemia saline gastrulae. The protein, designated HD40 to indicate a helix-destabilizing protein with a molecular weight of 40,000, is present in the high-salt ribosomal wash at a level of about 2 molecules per 80 S ribosome. The protein is monomeric at salt concentrations from 0.01 to 0.5 M and has an alpha-helix content of approximately 15%. The amino acid composition of HD40 is characterized by a high glycine content (19.5 mol%), the absence of cysteine, and the presence of the unusual amino acid dimethylarginine. The isolated protein binds preferentially to natural RNA over denatured DNA. HD40 inhibits protein synthesis directed by poly(rU) and by Artemia poly(A+) RNA in cell-free systems derived from Artemia and from wheat germ; inhibition is relieved by excess of mRNA. Single-stranded ribo- and deoxyribopolynucleotides are largely protected from degradation by nucleases when complexed with HD40. PMID- 6248524 TI - A single-stranded nucleic acid-binding protein from Artemia salina. II. Interaction with nucleic acids. AB - A helix-destabilizing protein, HD40 (Mr 40,000), isolated from the cytoplasm of Artemia salina (Marvil, D.K., Nowak, L., and Szer, W. (1980) J. Biol. Chem. 255, 6466-6472) stoichiometrically disrupts the secondary structures of synthetic single-stranded and helical polynucleotides (e.g. poly(rA), poly(dA), poly(rC), poly(dC), and poly(rU)) as well as those of natural polynucleotides (e.g. MS2 RNA and phi X174 viral DNA). The conformations of double-stranded DNA and double- or triple-stranded synthetic polynucleotides are not affected by the protein. Formation of duplexes, e.g. poly(rA . rU), is prevented by HD40 at 25 to 50 mM but not at 100 to 140 mM NaCl. The unwinding of the residual secondary structure of RNA and DNA by HD40 is not highly cooperative and has a stoichiometry of one HD40 per 12 to 15 nucleotides. The addition of HD40 in excess of 1 molecule per 12 to 15 nucleotides results in the cooperative formation of distinct bead-like structures along the nucleic acid strand. The beads are about 20 nm in diameter with a center to center distance of about 40 nm. The appearance of the beads is not accompanied by any spectral changes (CD and UV) beyond those obtained at a stoichiometry of one HD40 molecule per 12 to 15 nucleotides. PMID- 6248525 TI - Sequence-specific endonuclease Bam HI. Effect of hydrophobic reagents on sequence recognition and catalysis. AB - The specificity of cleavage of Bam HI is altered in the presence of hydrophobic reagents, such as glycerol and M2SO. The enzyme with altered specificity, designated Bam HI.1, generated digestion patterns of various DNAs, which were distinct from those generated by Bam HI. Cleavage sites recognized in phiX174 RF DNA in the presence of these hydrophobic reagents are not related to the Bam HI palindrome. Bam HI.1 appears to be an endogenous form of Bam HI that can be expressed by altering the hydrophobicity of the reaction. PMID- 6248526 TI - Dephosphorylation of the 20,000-dalton light chain of myosin by two different phosphatases from smooth muscle. PMID- 6248527 TI - NAD(P)H-dependent superoxide production by phagocytic vesicles from guinea pig and human granulocytes. PMID- 6248528 TI - Detection of activities that interfere with the enzymatic assay of deoxyribonucleoside 5'-triphosphates. AB - Several enzymes that interfere with the enzymatic assay of deoxyribonucleoside 5' triphosphates (dNTP's) are present as contaminants when nucleotides are extracted from HeLa cells with 60% methanol. These activities include a nuclease, nucleoside diphosphokinase, and deoxyribonucleoside monophosphokinases which phosphorylate dAMP, dGMP, and dCMP. Collectively, these enzymes are able to degrade and reutilize the DNA template which is used together with DNA polymerase for dNTP assays. This process introduces large errors when dNTP assays are performed in this manner. Attempts to block the enzymatic conversion of deoxyribonucleoside diphosphates to triphosphates by inhibition of nucleoside diphosphokinase were unsuccessful because of the inability to block completely the kinase activity. Acid extraction of nucleotides also results in the presence of an activity that interferes with the enzymatic dNTP assay. The error introduced by this interfering activity is much smaller than that arising from the enzymes present in methanol extracts. All of these interfering activities are removed when cells are first extracted with 60% methanol and the resulting extract is subsequently treated with perchloric acid. PMID- 6248529 TI - The conformation of cytochrome c in solution. Localization of a conformational difference between ferri- and ferrocytochrome c on the surface of the molecule. AB - The conformation of cytochrome c in solution is believed to change depending on the oxidation-reduction state of the heme iron, since ferri- and ferrocytochrome c exhibit several different physicochemical properties, but so far it is unknown if the conformational difference(s) is (are) confined to a particular part or domain of the molecule. We have therefore applied the method of differential chemical modification (Bosshard, H. R. (1979) Methods Biochem. Anal. 25, 273-304) to compare the chemical reactivity toward acetic anhydride of the 19 lysine residues of ferri- and ferrocytochrome c from horse heart. The epsilon-amino groups of the spatially related residues 39, 53, and 55 were significantly less reactive in ferrocytochrome c as compared to their reactivity in ferricytochrome c. The difference of reactivity was pH-dependent and was shown to be due to an increase of the pK values of the three epsilon-amino groups in ferrocytochrome c. These results indicate a local conformational change on the surface of the cytochrome c molecule in an area to the lower left of and below the heme cleft (standard front view of the molecule facing the exposed edge of the prosthetic group). The local conformational change might be instrumental in the cytochrome c mediated electron shuttle between cytochrome c1 and a in the final segment of the mitochondrial electron transport chain. PMID- 6248530 TI - Isolation and characterization of a ribonuclease activity specific for double stranded RNA (RNase D) from Krebs II ascites cells. AB - We have extensively purified from Krebs II ascites cells, although not until homogeneity, a ribonuclease which preferentially cleaves natural or synthetic double-stranded RNA substrates (RNase D); this specificity is also supported by its sensitivity to inhibition by 10(-5) M ethidium bromide. It does not degrade RNA-DNA hybrids and is, therefore, clearly distinct from previously characterized RNases H (Cathala, G., Rech, J., Huet, J., and Jeanteur, Ph. (1979) J. Biol. Chem. 254, 7354-7361). It shows no requirement for a divalent cation and is inhibited by all kinds of nucleic acids regardless of their secondary structure. It acts exclusively as an endonuclease, as shown by the analysis of degradation products, and yields 5'-phosphate termini. This enzyme is able to introduce discrete nicks into purified HeLa 45 S preribosomal RNA as well as into HeLa heterogenous nuclear RNA packaged within naturally occurring nuclear ribonucleoprotein particles. It is, therefore, an interesting candidate for an RNA-processing enzyme. PMID- 6248531 TI - The iron center in ribonucleotide reductase from Escherichia coli. AB - Ribonucleotide reductase from Escherichia coli consists of two nonidentical subunits, proteins B1 and B2. The active site is made up from both subunits. Protein B2 contains 2 iron atoms and a tyrosyl-free radical, which are essential for the enzymatic activity. The paramagnetic susceptibility of protein B2 has been measured over the temperature range 30-200 K. A deviation from the Curie law is observed at high temperatures, consistent with a structure of an antiferromagnetically coupled pair of high spin Fe(III) with an exchange coupling -J = 108(-20)+25 cm-1. Electronic spectra are resolved into components from the iron center and the radical. A band at 600 nm is clearly identified and shown to have contributions from both components. The electronic absorptions of the tyrosyl radical of protein B2 are closely similar to those reported for phenoxy radicals of tyrosine and tritertiary butyl phenol. Determinations by EPR of the amount of free radical suggest the possibility of more than one radical per active protein B2 molecule. Reconstitution of the active site from apoprotein B2 and Fe(II) is only observed in the presence of oxygen. With Fe(III), no reconstitution is obtained. The additional physical data on the iron center of protein B2 strengthen the analogy with oxidized forms of hemerythrin. The most likely structure is an antiferromagnetically coupled pair of high spin Fe(III), possibly with a bridging oxo-group. PMID- 6248532 TI - Purification and properties of a HeLa cell enzyme able to remove the 5'-terminal protein from poliovirus RNA. AB - Using a rapid phenol extraction assay, an enzyme was purified from uninfected HeLa cells that can cleave the 5'-terminal protein (VPg) from poliovirus RNA. Both cytoplasmic and nuclear extracts had enzymes with similar behavior. A polypeptide of molecular weight 27,000 was the major one present in the purified preparation. Assuming that this protein is the enzyme, a very low turnover number was calculated for it. The purified enzyme would cleave the tyrosine-phosphate bond linking VPg to poliovirus RNA with minimal degradation of the RNA or of VPg. If the RNA was first treated with proteinase K to degrade VPg, leaving a small peptide on the RNA, this peptide could also be removed by the enzyme. If the RNA was degraded with T1 RNase, leaving VPg attached to a nonanucleotide, the enzyme still would cleave off VPg, although incompletely. If the RNA was degraded completely, leaving either pUp or pU attached to VPg, the enzyme would not remove the nucleotides from the protein. Thus, for the enzyme to be active requires some length of polynucleotide attached to the protein but only a short peptide need be present for the enzyme to act. PMID- 6248533 TI - Adenovirus 2 early messenger RNA-genome mapping of 5'-terminal RNase T1 oligonucleotides and heterogeneity of 5'-termini. PMID- 6248534 TI - Characteristics of the action of human skin fibroblast collagenase on fibrillar collagen. PMID- 6248535 TI - Electron spin echo studies of cytochrome c oxidase. AB - We have studied the linear electric field effect in pulsed EPR of the "EPR detectable copper" signal of beef heart cytochrome c oxidase and have compared our results with those for a variety of square planar and tetrahedral Cu(II) model compounds and with Cu(II) proteins containing either type 1 or type 2 copper. The electric field induced g shifts (linear electric field effect) for cytochrome oxidase are comparable in magnitude to those for simple Cu(II) complexes and for some copper proteins containing type 2 sites. The shifts are smaller than those for tetrahedral copper complexes and for type 1 copper sites. However, the magnetic field dependence of the linear electric field effect does not resemble that observed for any Cu(II) complex studied nor for type 1 copper. These findings cannot be reconciled with the tetrahedral Cu(II) model proposed by Greenaway, Chan, and Vincow ((1977) Biochim. Biophys. Acta 490, 62-78, 1977) to explain the unusual EPR spectrum of cytochrome oxidase. PMID- 6248536 TI - The complete amino acid sequence of horse muscle acylphosphatase. AB - The amino acid sequence of horse muscle acylphosphatase is given in the present paper. The carboxymethylated enzyme consists of a single polypeptide chain of 98 amino acid residues with an acetyl group blocking the NH2 terminus and a tyrosine at the COOH terminus. The calculated molecular weight of the native protein, a mixed disulfide with glutathione, is 11,365. The carboxymethylated protein was cleaved by cyanogen bromide. The three expected fragments were purified; moreover, an additional fragment, derived from a partial failure of cleavage at methionine-24, was purified and characterized. The structures of the cyanogen bromide fragments were established by subfragmentation with endopeptidases, and the sequences of the overlapping subfragments were determined. From the results, it was possible to order the peptides within the sequence and then to establish the complete primary structure of the enzyme. PMID- 6248537 TI - Isolation of a Ca2+ carrier from calf heart inner mitochondrial membrane. AB - A protein has been isolated from calf heart inner mitochondrial membrane with the aid of an electron paramagnetic resonance (EPR) assay based on the relative binding properties of Ca2+, Mn2+, and Mg2+ to the protein. The molecular weight of this protein has been estimated to be about 3000 by urea/sodium dodecyl sulfate-gel electrophoresis and amino acid analysis. The isolated protein has been shown to have high affinity and high specificity for Ca2+ (Jeng, A. Y., Ryan T. E., and Shamoo, A. E. (1978) Proc. Natl. Acad. Sci. U. S. A. 75, 2125-2129). However, the protein was found to be contaminated with a large amount of phospholipids. There are 150 mol of phospholipids associated with each mole of the protein. The protein is delipidated using Sephadex LH-20 column chromatography. The contaminating phospholipids can be reduced to 0.1 mol of phospholipids/mol of protein. There are no detectable free fatty acids, hexosamines, or sialic acids associated with the delipidated protein. This protein is named "calciphorin," meaning calcium ionophore protein. PMID- 6248538 TI - Pregnant mare serum gonadotropin. An in vitro biological characterization of the lutropin-follitropin dual activity. PMID- 6248539 TI - tRNA binding stabilizes rat liver 60 S ribosomal subunits during treatment with LiCl. AB - We have shown recently that, in the absence of mRNA, 1 molecule of nonacylated tRNA binds to the large ribosomal subunit of rat liver with a high affinity constant (Buisson, M., Reboud, A.M., Dubost, S., and Reboud, J. P. (1979) Biochem. Biophys. Res. Commun. 90,634-640). In this paper, free and tRNA-bound 60 S subunits were treated with increasing concentrations of LiCl to obtain information on tRNA binding site. The rationale for using deacylated tRNA was that it is assumed to bind to the peptidyl donor site. We observed that tRNA has a strong protective effect on subunit modifications produced by LiCl: tRNA prevents subunit inactivation as measured by puromycin reaction and polyphenylalanine synthesis and it shifts the Li+/Mg2+ ratio value needed to reach 50% inactivation, from 60 to 250; it also prevents ribosomal protein and 5 S RNA release and large sedimentation changes of subunits, induced by LiCl. To explain the mechanism of 60 S subunit stabilization by tRNA, two hypotheses are considered: stabilization can be consequent on direct interaction of tRNA with specific proteins, or on maintenance on subunits of essential cations which are otherwise displaced by Li+, or both. PMID- 6248540 TI - Alignment of the peptides derived from acid-catalyzed cleavage of an aspartylprolyl bond in the major internal structural polypeptide of avian retroviruses. AB - The major internal structural polypeptide (p27) of Rous sarcoma virus (RSV), and the analogous polypeptide (P27(0)) OF Rous-associated virus-O (RAV-O), an endogenous virus released spontaneously by some chicken cells) have been cleaved selectively at a single aspartylprolyl peptide bond to yield two fragments. The NH2- and COOH-terminal amino acid sequences of p27 and p27(0) and their mild acid cleavage fragments have been determined. These results show the existence of an identical cleavage site and a similar NH2- and COOH-terminal amino acid sequence in both the polypeptides. Furthermore they indicate that the difference in the molecular weights of p27 and p27(0) results from an insertion of amino acids in the COOH-terminal peptide of p27(0) rather than a shift in the scission site of the precursor molecule. PMID- 6248541 TI - Isolation and characterization of a putative bacteriophage T5 transcription.replication enzyme complex from infected Escherichia coli. AB - A well defined enzyme comples of approximately 5 X 10(6) daltons that contains phage and host cell components known to be required for the processes of phage transcription and DNA replication has been isolated from bacteriophage T5 infected Escherichia coli cells. In addition to the RNA polymerase of the host cell, the complex contains the phage-encoded: gpC2 which has been implicated genetically as a controlling element of late transcription; gpD9, the DNA polymerase required for T5 DNA replication; the proteins gpD5 (DNA-binding protein), and gpD15 (nuclease) which are both known to be essential for T5 DNA replication and for the initiation of late transcription. The viral gpD5 derived from the purified complex is a phosphoprotein. The enzyme complex also contains, protected from the action of nuclease, double-stranded DNA with an approximate molecular weight of 1 to 2 X 10(6) (2 to 3% of the size of the T5 genome) which is derived preferentially from the center of the T5 DNA molecule. The composition of the enzyme complex suggests that the processes of transcription and replication are integrated in T5-infected cells. PMID- 6248542 TI - Structural analysis of cGMP-dependent protein kinase using limited proteolysis. AB - cGMP-dependent protein kinase from bovine lung is labile to specific proteolysis. Limited digestion with chymotrypsin produces a 65,000-dalton monomer and a 16,000 dalton dimer from a 150,000-dalton dimeric enzyme. The larger proteolytic fragment represents the COOH-terminal portion of the enzyme and contains the catalytic site along with the cGMP binding site. The smaller fragment representing the NH2-terminal portion of the enzyme contains the autophosphorylation site and the interchain disulfide bond(s). A model defining the functional domains of cGMP-dependent protein kinase is presented and comparisons with cAMP-dependent protein kinase regulatory subunit are discussed. PMID- 6248543 TI - Proline isomerism in the protein folding of ribonuclease A. AB - The guanidinium chloride-unfolded state of ribonuclease A was found to be an equilibrium mixture of slow- and fast-refolding forms of the protein chain, as has been suggested. Both forms appear to have the same spectroscopic observables as judged by the relative changes in fluorescence emission and polarization. The equilibrium between them is thermally dependent, with deltaHapp equal to -1.4 kcal/mol. The activation energy Ea is equal to 18 kcal/mol. These findings are consistent with the proposal that cis-trans isomerism of peptide bonds that are NH2-terminal to proline residues is responsible for the slow phase of RNase A refolding. However, the actual dependence of the magnitude of the slow reaction on initial, prefolding temperature cannot be explained by a model in which the proline configurations of the fast refolding form must be identical to those of the native protein, as has been suggested. Instead, the data reveal that, although the native structure of RNase A contains two cis prolines, cis isomers need not be present in the fast-refolding form in order for folding to occur. PMID- 6248544 TI - Two different intrachain cAMP binding sites of cAMP-dependent protein kinases. AB - The regulatory subunits of both isozymes of cAMP-dependent protein kinase bind 2 mol of cAMP/mol of monomer. cAMP dissociation studies indicate similar cAMP binding behavior for each isozyme. Each has two different intrachain cAMP binding components present in approximately equal amounts and the rate of cAMP dissociation is 5- to 10-fold slower from one site (Site 1) than from the other (Site 2). Equilibrium [3H]cAMP binding is inhibited by several competing cyclic nucleotides. Following equilibrium binding using saturating [3H]cAMP in the presence of competing nucleotide, the pattern of release of [3H]cAMP, monitored in the presence of an excess of nonradioactive cAMP, suggests site-specific selectivity of some of the cyclic nucleotides. As compared with cAMP, cIMP prefers Site 2 for both regulatory subunits, whereas N6, O2-dibutyryl-cAMP shows a similar preference only with isozyme II regulatory subunit. 8-Bromo-cAMP, 8 bromo-cGMP, and 8-azido-cAMP prefer Site 1 of both proteins. The results indicate that for each isozyme the two intrachain binding sites have different analogue specificities and cAMP dissociation rates. Site 1 or Site 2 of one isozyme has a similar but not identical cyclic nucleotide specificity and cAMP dissociation rate to the corresponding site of the other isozyme. PMID- 6248545 TI - Presence of a proteolytic activity in murine mammary tumor virus. PMID- 6248546 TI - A ternary complex model explains the agonist-specific binding properties of the adenylate cyclase-coupled beta-adrenergic receptor. AB - The unique properties of agonist binding to the frog erythrocyte beta-adrenergic receptor include the existence of two affinity forms of the receptor. The proportion and relative affinity of these two states of the receptor for ligands varies with the intrinsic activity of the agonist and the presence of guanine nucleotides. The simplest model for hormone-receptor interactions which can explain and reproduce the experimental data involves the interaction of the receptor R with an additional membrane component X, leading to the agonist promoted formation of a high affinity ternary complex HRX. Computer modeling of agonist binding data with a ternary complex model indicates that the model can fit the data with high accuracy under conditions where the ligand used is either a full or a partial agonist and where the system is altered by the addition of guanine nucleotide or after treatment with group-specific reagents, e.g. p hydroxymercuribenzoate. The parameter estimates obtained indicate that the intrinsic activity of the agonist is correlated significantly with the affinity constant L of the component X for the binary complex HR. The major effect of adding guanine nucleotides is to destabilize the ternary complex HRX from which both the hormone H and the component X can dissociate. The modulatory role of nucleotides on the affinity of agonists for the receptor is consistent with the assumption that the component X is the guanine nucleotide binding site. The ternary complex model was also applied successfully to the turkey erythrocyte receptor system. The model provides a general scheme for the activation by agonists of adenylate cyclase-coupled receptor systems and also of other systems where the effector might be different. PMID- 6248547 TI - Differential effects of single and repeated administrations of gonadotropins on luteinizing hormone receptors and testosterone synthesis in two populations of Leydig cells. PMID- 6248548 TI - Covalent modification of the active site of carbamyl phosphate synthetase by 5'-p fluorosulfonylbenzoyladenosine. Direct evidence for two functionally different ATP-binding sites. PMID- 6248549 TI - Mechanism of primer-template-dependent conversion of dNTP leads to dNMP by T5 DNA polymerase. AB - T5 DNA polymerase catalyzes both 5' leads to 3' polymerization and 3' leads to 5' hydrolysis in a processive fashion. This knowledge has been utilized to obtain evidence indicating that the enzyme has a single primer-template binding site which can function as either polymerase or exonuclease, perhaps with the cooperation of additional or different side groups. Template-dependent conversion of dNTP leads to dNMP was observed with an excess of either primer-template or enzyme. With primer-template excess, practically all the enzymes were functional as polymerase; with enzyme excess, all primer-templates were extended during the first cycle of catalysis. These observations suggest that turnover takes place at the points of chain growth. Evidence is also provided which demonstrates that the enzyme is capable of switching its direction of catalysis from 3' leads to 5' to 5' leads to 3' without leaving the primer-template. A clear correspondence between the relative amount of hydrolysis of a terminally labeled residue on the primer and the relative amount of turnover suggests that (a) the probability of hydrolysis of a given type of residue in contact with the "active site" is constant, and (b) during each turnover episode enzyme usually takes only one step in the 3' leads to 5' direction. A simple probabilistic model of turnover is discussed. PMID- 6248550 TI - Formation of an iso-1-cytochrome c-like species containing a covalently bonded heme group from the apoprotein by a yeast cell-free system in the presence of hemin. AB - Incubation of the 125I-labeled apoprotein, prepared from 125I-labeled iso-1 cytochrome c, with a yeast mitochondrial fraction in the presence of hemin, NADPH, and an extract of the postmitochondrial fraction at 32 +/- 1 degree C for 30 min has resulted in formation of cytochrome c-like species in yields of up to 35%. This radioactive synthesized species contains a functional group which responds to reduction with ascorbate and oxidation with K3Fe(CN)6 in that it is resistant in the reduced form and susceptible in the oxidized form to trypsin action in a manner characteristic of native cytochrome c. The functional group cannot be removed from the protein by cold HCl-acetone or 8 M urea treatment. The reduced form of the synthesized species exhibits resistance against autoxidation and the oxidized form can be reduced also by cytochrome b2. The synthesized species exhibits the same compact hydrodynamic volume of native cytochrome c. Treatment with silver sulfate followed by incubation with dithiothreitol converts the synthesized species to the original apoprotein as judged by an increase in the hydrodynamic volume. Thus, the synthesized species is indistinguishable from the original labeled iso-1-cytochrome c by these measurements; i.e. the synthesized species consists of the apoprotein to which heme is covalently attached through the thioether bond(s). The active factor of the mitochondrial fraction is heat-labile. The synthetic activity is strongly dependent on pH with a maximum approximately at pH 7.0. Hemin (or heme) appears to be required for this synthesis. The postmitochondrial fraction is inactive by itself. However, its addition markedly increases the synthetic activity. This factor is heat stable, soluble in 80% methanol (or 75% ethanol), and insoluble in ethyl ether or ethyl acetate. Addition of NADP(H) (or NAD(H)) also increases the synthetic activity, the reduced form being more effective than the oxidized form. The postmitochondrial factor and the pyridine nucleotides appear to enhance the effect of each other. Thus, it seems that cytochrome c or a cytochrome c-like species is formed from the apoprotein and heme (or hemin) by an enzyme, cytochrome c synthetase, present in mitochondria. PMID- 6248551 TI - Phosphorylation of acyclovir (acycloguanosine) monophosphate by GMP kinase. PMID- 6248552 TI - Reduced cytochrome c oxidase. A new form absorbing at 443 and 603 nm. AB - Reduced cytochrome c oxidase is known to absorb strongly at 445 nm and 605 nm regardless of the chemical or physiological nature of the reductant. When the reduced oxidase is allowed to interact with cytochrome c3 under conditions in which there is no net change in the oxidation state of the oxidase, the absorption bands shift from those commonly found to 443 nm and 603 nm. This new oxidase form is postulated to be the intermediate in the catalytic cycle of the oxidase that results in the formation of the 418-nm form of the oxidized oxidase; it is further postulated that the 445-nm form is the intermediate in the catalytic cycle that results in the 428-nm form of the oxidized oxidase. The relevance of the 443-nm, 603-nm form to the conformational cycle of the oxidase as well as its possible involvement in energy transduction at Site II of oxidative phosphorylation are discussed. PMID- 6248553 TI - On the mechanism whereby ACTH and cyclic AMP increase adrenal polyphosphoinositides. Rapid stimulation of the synthesis of phosphatidic acid and derivatives of CDP - diacylglycerol. PMID- 6248554 TI - A unique cyclic nucleotide-dependent protein kinase. AB - During the course of studying the soluble cyclic nucleotide-dependent protein kinases of a developing insect, three different enzymes were isolated. Two of these were found to be cAMP-dependent enzymes eluting from DEAE-cellulose in a manner identical with protein kinases I and II found in vertebrate muscle. The third enzyme appears to be unique. It has high affinity for either cAMP or cGMP (KA of 43 nM and 25 nM, respectively), the only cyclic nucleotide-dependent kinase described, to have this property. The enzyme has lower affinity for cIMP and cCMP (KA of 160 nM and 340 nM, respectively). Binding to cyclic nucleotide does not alter enzyme size. The KM for ATP is 86 microM, and among several types of histones tried, the slightly lysine-rich subgroup f2a was the best phosphate acceptor. Maximum activity was obtained with 1 mM Mg2+ while Mn2+ was completely ineffective. This new enzyme was purified to homogeneity on a cAMP affinity column as judged by two-dimensional electrophoresis. On the basis of molecular sieving and sodium dodecyl sulfate electrophoresis we have reached the preliminary conclusion that the native enzyme is a dimer of identical subunits with a molecular weight of 180,000. If the mammalian cAMP and cGMP enzymes are indeed homologous proteins, perhaps we have in this new kinase a species that represents a common ancestral protein. PMID- 6248555 TI - Inactivation of the opiate receptor in bovine caudate nucleus by azide enkephalin analogs. AB - Photoaffinity labels have been prepared to react with the opiate receptor. The compounds are based on analogs of the enkephalins but involve significant changes in structure which allow introduction of azido substituents while still retaining binding affinity. The compounds designed have been shown to have biological activity in guinea pig ileum tests. A good correlation is obtained between the Kd for stereospecific binding and the Kd for activity in the guinea pig test. Affinity to and inactivation of the opiate receptor is obtained with two of the compounds which have affinities and activities comparable to morphine. PMID- 6248556 TI - Catecholamine-specific desensitization of adenylate cyclase. Evidence for a multistep process. PMID- 6248557 TI - In vitro regulation of kidney 25-hydroxyvitamin D3-hydroxylase enzyme activities by vitamin D3 metabolites. Molecular specificity and mechanism of action. AB - An acute chick kidney tubule model was used to evaluate the molecular specificity of steroids which act to inhibit kidney 25-hydroxyvitamin D3-1-hydroxylase and induce 25-hydroxyvitamin D3-24-hydroxylase enzyme activities. Such hydroxylase regulatory activity was confined to the vitamin D family of secosteroids. Vitamin D3 per se was not active. Rather, expression of hydroxylase-regulatory activity required acquisition of a C-25 hydroxyl grouping. Of the metabolites tested, 25 hydroxyvitamin D3 demonstrated the greatest hydroxylase-regulatory activity. Metabolites of 25-hydroxyvitamin D3 which contained hydroxyl groups at carbon atoms 1, or 24, or both, were also active in regulating the kidney hydroxylase enzymes. The hydroxylase-regulatory action of 1,25-dihydroxyvitamin D3 was blocked by inhibitors of RNA or protein synthesis, implicating a requirement for de novo protein synthesis. It was suggested that the regulatory process involves both hydroxylase-enzyme synthesis and turnover as well as enzyme-level modulation of endogenous enzyme activities. PMID- 6248558 TI - Reconstitution of the iron-sulfur protein responsible for the g = 1.90 electron paramagnetic resonance signal and associated cytochrome c reductase activities to depleted succinate-cytochrome c reductase complex. PMID- 6248559 TI - Protein rotational mobility and lipid fluidity of purified and reconstituted cytochrome c oxidase. PMID- 6248560 TI - Anterior transposition of the ulnar nerve using a non-compressing fasciodermal sling. AB - Sixteen elbows of fourteen patients were analyzed five to sixty months after treatment for ulnar neuritis or neuropathy by anterior transposition of the ulnar nerve using a non-compressing fasciodermal sling to maintain the anterior position. This procedure creates a septum in the mid-lateral plane that lies posterior to the transposed nerve at the level of the medial epicondyle. Unlike previous procedures, no structure other than subcutaneous fat is located superficial to the nerve. Seven patients were baseball pitchers who had experienced transient but severe ulnarnerve paresthesias during the act of throwing. Of the sixteen extremities only one, the limb of a severely diabetic patient with bilateral ulnar neuropathy, was not relieved of preoperative complaints. There were no complications. The procedure is simple, postoperative immobilization is needed for only a brief period, and rehabilitation is rapid. PMID- 6248561 TI - Comparative study of tumorigenicity in mice administered transplacentally or neonatally with metabolites of tryptophan and its related compounds. AB - Intermediate metabolites of tryptophan, 3-hydroxy-L-kynurenine (3-OHKY), 3 hydroxyanthranilic acid (3-OHAA) and anthranilic acid (AA), and an enzyme inhibitor from 3-OHKY to 3-OHAA, isonicotinic acid hydrazide (INH) with or without 3-OHKY at the maximum tolerated dose were injected s.c. to infant CDF1 mice. AA and 3-OHAA were tested transplacentally for tumorigenicity. Animals treated were observed for 1 year. Hepatocellular adenoma was developed at the incidence of 21.7% in male mice administered with 3-OHKY and INH as compared with 5.6% incidence in control males, but no leukemia was induced. Incidences of lung (3.4--15.0%) and liver tumors (4--5%) in other groups treated at infant stage were comparable to that in controls (lung: 11.1%; liver: 5.6%). Other tumors were one angiogenic sarcoma in a female treated with 3-OHAA, and one granulosa cell tumor of ovary in female treated with INH. Transplacentally the 10.3% incidence of liver tumor in male offspring, whose mothers were treated with AA, was slightly higher than that in male control (5.6%). However, the incidences of tumor were apparently in a critical level in these experimental conditions. PMID- 6248562 TI - Histological and immunocytochemical examinations of the stromal reaction in carcinomas of the parotid gland. Analysis of 52 cases. PMID- 6248563 TI - Peripheral neuropathy and ophthalmologic toxicity after treatment with cis dichlorodiaminoplatinum II. AB - A 57-year-old woman with inoperable bladder cancer received radiation treatment. Thirteen years later she relapsed at locoregional, retroperitoneal, and mediastinal sites. During treatment with cis-dichlorodiamineplatinum II (DDP) (30 mg/day for 5 days repeated every 4 weeks) she achieved a partial remission. After seven courses of DDP-chemotherapy she complained of numbness of her hands and legs and of diminished visual acuity of both eyes. After 4 weeks these symptoms grew less but intensified severely after another DDP-treatment. The temporal relationship of neurologic symptoms and their intensification by the last administration of DDP suggest this drug to be the causative agent for peripheral neuropathy and ophthalmologic toxicity. PMID- 6248564 TI - Dissociation of opsonized particle phagocytosis and respiratory burst activity in an Epstein-Barr virus-infected myeloid cell line. AB - A continuous tissue culture cell line (Karpas line 120), derived from a patient with acute myeloblastic leukemia, not only demonstrates myeloblastic morphology and in vitro expression of several myeloid-specific biochemical markers but also contains Epstein-Barr virus (EBV) nuclear antigen. The present studies demonstrate EBV-genome-specific DNA within the total cellular DNA by molecular hybridization, thus establishing the presence of stable viral genome integration. The cells demonstrate complex coordinated myeloid functions including ingestion, degranulation, and respiratory burst activity. Line 120 cells show a respiratory burst (superoxide and hydrogen peroxide generation and hexosemonophosphate shunt activity) in response to soluble (phorbol myristate acetate) and particulate (latex beads) stimuli, as do normal granulocytes. They ingest complement opsonized particles (lipopolysaccharide-oil droplets, zymosan, and bacteria), and degranulate in response to them. However, unlike normal granulocytes, the line 120 cells do not demonstrate respiratory burst activity in response to these complementopsonized particles. The dissociation between ingestion of complement opsonized particles and activation of oxygen-dependent bactericidal activity severely impairs bacterial killing as compared with normal polymorphonuclear phagocytes. PMID- 6248566 TI - Induction of the acrosome reaction in guinea pig spermatozoa by cGMP analogues. AB - The effect of cyclic nucleotide analgoues upon the immediate induction of the guinea pig acrosome reaction (AR) was studied. Dibutyryl (dB) CGMP and 8-bromo cGMP, when added to sperm suspensions after varying periods of preincubation in glucose-free BWW medium (NaCl 94.59 mM, KCl 4.7 mM, CaCl2 1.71 mM, KH2PO4 1.19 mM, MgSO4 1.19 mM, NaHCO3 25.07 mM, pyruvate 0.25 mM, lactate 21.58 mM, and bovine seru albumen 1 g/liter), induced the AR in a large proportion of spermatozoa relative to controls. The proportion of ARs induced upon the addition of dB cGMP or 8-bromo-cGMP (10mM) at 1 h was equivalent to that obtained after a 5-h incubation in glucose-free BWW alone. The effect of cGMP analogues was concentration dependent over the tested range of 2-12 mM (less than 1-20%). The simultaneous addition if imidazole (10 mM), a cAMP phosphodiesterase stimulator, potentiated the effect (imidazole + 12 mM 8-bromo-cGMP: 73%). cAMP analogues were without effect. The presence of extracellular Ca++ was required, and it is suggested that a rise in the cGMP/CAMP ratio triggers Ca++ influx and the AR. PMID- 6248565 TI - Integrated stereological and biochemical studies on hepatocytic membranes. I.V. Heterogeneous distribution of marker enzymes on endoplasmic reticulum membranes in fractions. AB - The purpose of the study was to consider quantitatively the relationships between the surface area of the endoplasmic reticulum (ER) and constituent marker enzyme activities, as they occur in fractions collected from rat liver homogenates. The ER surface area was estimated in five membrane-containing fractions by use of a combined cytochemical-stereological technique (5), while, at the same time, ER marker enzymes were assayed biochemically. Fraction/homogenate recoveries for the ER enzymes averaged 100%, total membrane surface area 98%, and ER surface area 96%. Relative specific activities, which compare the relative amounts of ER marker enzyme activities to the relative ER surface area in the membrane containing fractions, indicate variable distributions for glucose-6-phosphatase and NADPH cytochrome c reductase, but not for esterase. PMID- 6248567 TI - In vitro fusion of Acanthamoeba phagolysosomes. III. Evidence that cyclic nucleotides and vacuole subpopulations respectively control the rate and the extent of vacuole fusion in Acanthamoeba homogenates. AB - Fusion of phagolysosomes has been previously demonstrated to occur during the incubation of phagolysosome-containing homogenates of Acanthamoeba (Oates and Touster, 1978, J. Cell Biol. 79:217-234). Further studies on this system have shown that methylxanthines (0.2 mM) and/or cAMP (0.5-1 mM) markedly accelerate the average rate, but not the extent, of the in vitro phagolysosome fusion process. Adenosine, 5'-AMP, and ADP (0.5-1 mM) were without effect. ATP (0.5-1 mM) caused variable stimulation, whereas beta, gamma-methylene-ATP (1 mM) caused pronounced inhibition, as did GTP (1 mM) and cGMP (1 mM). Stimulation by 3 isobutyl-1-methylxanthine was blocked by GTP, but not by ATP or cAMP. These results indicate that the rate of phagolysosome fusion in Acanthamoeba homogenates may be regulated by cyclic nucleotides, with enhancement of the fusion rate by cAMP and inhibition of the rate by cGMP. The extent of the reaction increased spontaneously and markedly during the first few hours after preparation of the homogenates. This activation appears to be because of a slow conversion of a significant fraction of the vacuole population from a fusion incompetent to a fusion-competent, cyclic nucleotide-sensitive state. PMID- 6248568 TI - Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue. AB - A novel method has been developed for the preparation of nearly pure separate cultures of astrocytes and oligodendrocytes. The method is based on (a) the absence of viable neurons in cultures prepared from postnatal rat cerebra, (b) the stratification of astrocytes and oligodendrocytes in culture, and (c) the selective detachment of the overlying oligodendrocytes when exposed to sheer forces generated by shaking the cultures on an orbital shaker for 15--18 h at 37 degrees C. Preparations appear greater than 98% pure and contain approximately 1 2 x 10(7) viable cells (20--40 mg of cell protein). Three methods were used to characterize these two culture t ypes. First, electron microscopic examination was used to identify the cells in each preparation (mixed and separated cultures of astrocytes and oligodendrocytes) and to assess the purity of each preparation. Second, two oligodendroglial cell markers, 2',3'-cyclic nucleotide 3' phosphohydrolase (EC 3.1.4.37) and glycerol phosphate dehydrogenase (EC 1.1.1.8) were monitored. Third, the regulation of cyclic AMP accumulation in each culture type was examined. In addition to these studies, we examined the influence of brain extract and dibutyryl cAMP on the gross morphology and ultrastructure of each preparation. These agents induced astroglial process formation without any apparent morphological effect on oligodendrocytes. Collectively, the results indicate that essentially pure cultures of astrocytes and of oligodendrocytes can be prepared and maintained. These preparations should significantly aid in efforts to examine the biochemistry, physiology, and pharmacology of these two major classes of central nervous system cells. PMID- 6248569 TI - Evidence for a pronounced secretion of cyclic AMP by Tetrahymena. AB - The unicellular eukaryote Tetrahymena pyriformis secretes significant amounts of cyclic AMP into its external medium. Cells transferred from growth medium into any of the following three different non-nutrient media: (a) 5 mM phosphate buffer containing 47 mM NaCl and 1 mM MgSO4, (b) 10 mM Tris, or (c) 1.3 mM Tris containing 1 mM citrate and 1 mM Ca(OH)2, released to the outside almost 60--80% of the total cyclic AMP produced during 2--5 h of incubation. Tris-citrate-Ca+2 medium was chosen for further experiments because of its minimal nonspecific interference in the cyclic AMP radioimmunoassay. The identity of the secreted material recognized as cyclic AMP by radioimmunoassay was confirmed by demonstrating its almost complete hydrolysis with commerical beef heart phosphodiesterase. Furthermore, the radioimmunoassay-active material in the concentrated medium co-chromatographed on paper with [3H]cyclic AMP, as judged by assay of the eluted material. After resuspending cells in Tris-citrate-Ca2+ medium, the extracellular concentration of cyclic AMP rose steadily over a 5-h period, reaching a level equvalent to approximately 35--50 pmol cyclic AMP/10(6) cells vs. an internal cyclic AMP quantity at 5 h of 8--10 pmol/10(6) cells. After 5 h, the level of extracellular cyclic AMP reached a plateau. There was no degradation or uptake of external cyclic AMP by the cells during this period. PMID- 6248570 TI - Cholera toxin and analogues of cyclic AMP stimulate the growth of cultured human mammary epithelial cells. AB - The growth of human epithelial cells is stimulated by cholera toxin and analogues of cyclic AMP, while the growth of breast derived fibroblasts is inhibited. These compounds have little effect on DNA synthesis in the absence of other mitogens but show a synergistic effect with serum and/or EGF. The results suggest that high intracellular levels of cyclic AMP in human mammary epithelial cells increase the growth response of the cell to mitogens. PMID- 6248571 TI - NAD turnover in microplasmodia of physarum polycephalum. AB - The rate of NAD turnover in microplasmodia of Physarum polycephalum was investigated using a double labeling technique with (14C)-adenine or adenosine and (3H)-nicotinamide. The half-life of an NAD molecule in Physarum was estimated to be 25 min, which is shorter than in either E. coli or human cell lines. The half-life of NAD in the presence of an inhibitor of NADase and poly ADPR synthase, 5-methylnicotinamide, was also investigated, but found to be indistinguishable from controls. The possible reasons for this and for the rapid turnover is discussed in the light of the known functions for NAD in prokaryotes and eukaryotes. PMID- 6248572 TI - Determination of disulfiram and metabolites from biological fluids by high performance liquid chromatography. AB - A high-performance liquid chromatographic method is described for the determination of disulfiram, diethyldithiocarbamate, diethyldithiocarbamate methyl ester, carbon disulfide, and diethylamine from a single sample of plasma or urine. The analytical procedure is based on a quantitative stepwise extraction of disulfiram and diethyldithiocarbamate methyl ester, or the conversion of diethyldithiocarbamic acid, carbon disulfide and diethylamine to diethyldithiocarbamate methyl ester for chromatographical determination. The procedure is specific, precise and simple. The application of the analytical methods developed for the determination of disulfiram and the various metabolites in plasma from mice given disulfiram intraperitoneally or humans given Antabuse orally is illustrated. PMID- 6248573 TI - Reversed-phase high-performance liquid chromatographic purification and characterization of the adrenocorticotropin/lipotropin precursor and its fragments. AB - Methods are presented for the effective purification by reversed-phase high performance liquid chromatography (HPLC) of rat adrenocorticotropin/lipotropin (ACTH/LPH) precursor and its two glycosylated forms. Purification of its NH2 terminal segment from human and porcine pituitaries is presented together with microsequencing data confirming the identity of the purified peptides. The effective separation of various native fragments related to ACTH and beta-LPH from sheep pituitaries is presented. A new putative gamma-MSH hormone has been synthesized and purified by reversed-phase HPLC and tryptic peptide mapping performed to establish the identity of the purified peptide. PMID- 6248574 TI - Serological comparisons of avian reoviruses. PMID- 6248575 TI - The effects of challenge with homologous and heterologous strains of Border disease virus on ewes with previous experience of the disease. PMID- 6248576 TI - Mechanisms of natural transmission of Border disease. PMID- 6248577 TI - Infection of pregnant sheep with the NADL strain of bovine virus diarrhoea virus and their subsequent challenge with Border disease IIB pool. PMID- 6248578 TI - Susceptibility of the horse to experimental inoculation with louping ill virus. PMID- 6248579 TI - Morphogenesis of hydranencephaly and other intracranial malformations in progeny of pregnant ewes infected with pestiviruses. PMID- 6248580 TI - Cytopathic and immunogenic studies of sheep pox virus serially cultivated in cell culture. PMID- 6248581 TI - Use of liposoluble contrast material to separate left renal and splenic parenchyma on computed tomography. AB - A lobulated or accessory spleen lying against the upper pole of the left kidney may simulate renal tumor on computed tomograms. Water soluble contrast material is usually of little help in the differential diagnosis, since it increases the attenuation of both the kidney and the spleen. Intravenous liposoluble contrast material preferentially increases the attenuation of the liver and spleen and thus permits clear separation of the enhanced lobulated or accessory spleen from the unopacified renal parenchyma. PMID- 6248582 TI - Chemistry and utilization of phenylpropanoids including flavonoids, coumarins, and lignans. PMID- 6248583 TI - Cucurbit seed coat composition. PMID- 6248584 TI - Multielement absorption by crops grown on soils amended with municipal sludge ashes. PMID- 6248585 TI - Availability of metals in irradiated sewage sludge. PMID- 6248586 TI - Metastatic mucous-producing adenocarcinoma of the gingiva. AB - An unusual metastasis of adenocarcinoma of the lung to the gingival mucosa in a 75-year-old man is reported. The case presents an interesting differential clinical assessment as the gingival lesions seem to be of local nature and involve a combined endodontic-periodontic causation. PMID- 6248587 TI - Bran as a source of dietary fiber in oatmeal cookies. AB - A panel of 1,542 Michigan consumers found oatmeal cookies in which 50 per cent of the flour was replaced with ground red or white wheat bran and a control cookie similarly acceptable. Cookie buying habits, consumer awareness of dietary fiber, and their methods of increasing it were cross-tabulated with demographic data. PMID- 6248588 TI - Thyrotropin-induced increase in phosphoprotamine phosphatase activity in rat thyroid. AB - Phosphoprotamine phosphatase activity in the rat thyroid was examined by studying the release of inorganic phosphate from [32P]-phosphorylated protamine. Rats were given a normal diet supplemented or not with thyroxine (T4) (3 mg/l in 0.05% bovine serum albumin solution) or propylthiouracil (1 g/l in 1% sucrose solution) in drinking water for various periods. TSH was injected ip, 100 mU per animal. A significant increase of phosphatase specific activity-units per mg protein (3 fold) as well as units per gland- was observed following goitrogen treatment, whereas a decrease (50%) was seen in response to T4. Both the soluble and particle activities were similarly affected. As total activity decreased after T4 treatment, it appeared that only the Mn2+-stimulating enzyme was concerned, the Mn2+-unstimulated part remaining unaltered. In vitro cyclic AMP or cyclic GMP at concentrations from 10 micro M to 200 micro M had no effect on these phosphatase activities. TSH injected in chronically T4-treated rats (32 days treatment) failed to produce any significant enhancement in phosphatase activity whatever the time of injection before sacrifice (from 2 to 6 h). On the contrary a single injection of TSH in animals subjected to short treatment with T4 (2 days) induced an elevation of the enzyme activity, restoring partially the initial level. These findings suggest that TSH controls protein dephosphorylation activities in the thyroid. Furthermore, they offer additional evidence that prolonged T4 administration leads to decreased responsiveness to TSH. PMID- 6248589 TI - Serum 21-deoxycortisol and 17-hydroxypregnenolone in parents of patients with congenital adrenal hyperplasia. AB - The response of serum 21-deoxycortisol (21-DF), 17-hydroxypregnenolone (17-OHPE), 11-deoxycortisol and cortisol to iv ACTH, was compared in 14 adult controls ane and post stimulation concentrations of hormones were similar in controls and parents, except for those of 21-DF, which were significantly greater in heterozygotes 30 min (p less than 0.005), 60 min (p less than .0025) and 90 min (p less than 0.005) after stimulation with ACTH. When rates of increase were determined, those of 21-DF at 30, 60 and 90 min were significantly higher in the parents. Sixteen of the 26 parents (62%) had a rate of increase of 21-DF from 0 to 60 min greater than the mean plus two standard deviations of the control group. Using this same criteria, 11 of the 13 mothers (85%) of affected children could be identified as heterozygotes. The rate of increase of 21-DF from 0 to 60 min following ACTH provides a method for the detection of some heterozygote carriers of congenital adrenal hyperplasia and may be useful particularly in the identification of female carriers. PMID- 6248591 TI - Cytochemical study of concanavalin A binding sites and their mobility in normal, cystic fibrosis, and SV40 transformed human fibroblasts in vitro. AB - Concanavalin A (Con A) binding sites and their mobility were studied by peroxidase (Po) and ferritin labeling techniques in normal and SV40 transformed human fibroblasts. Binding sites were visualized either as osmium black of 3'3 diaminobenzidine (DAB) reactions or as ferritin particles. DAB reaction products were localized at the external surface of the plasma membrane and in some multivesicular bodies of fixed cells. The labeling was continuous in normal and SV40 transformed human fibroblasts. When living cells were treated with Con A-Po at 4 degrees C and incubated at 37 degrees C, both normal and transformed cells showed remarkable changes. The foci of membrane indentations (caps or patches) are formed on the cell surface. Many labeled internalized vacuoles and vesicles appeared within the cytoplasm and in close proximity to the Golgi region of all cell types. The cellular changes occurred more quickly in transformed cells than in normal cells. It is concluded that normal cells do cap under certain conditions and that the plasma membranes of transformed cells are more fluid than those of normal cells. PMID- 6248590 TI - Rhythm characteristics of plasma renin, aldosterone and cortisol in five subtypes of mesor-hypertension. AB - The possible role of the renin-angiotensin system and ACTH in controlling the temporal organization of circadian rhythm of aldosterone was studied in patients with mesor-hypertension (MH) by simultaneous radioimmunological determinations of within-day changes in plasma renin, aldosterone and cortisol. Thirty-nine uncomplicated, untreated mesor-hypertensive patients, divided in subtypes, were examined. The interrelationship between the rhythm components revealed that the circadian cyclicity of aldosterone in both mesor-normotensive and mesor hypertensive subjects, with either normal or high renin patterns, has a similar timing in acrophase with renin periodicity, which leads the circadian cortisol rhythm. In low-renin mesorhypertensive subjects a circadian rhythm of aldosterone and cortisol, but not of renin, remains demonstrable. The confidence limits of the estimated acrophase for circadian cortisol rhythm do not, however, overlap the confidence arcs of the aldosterone phase. These findings suggest that in normal or high renin MH subjects the aldosterone rhythmicity is mainly controlled by the renin-angiotensin system. Conversely in low-renin MH subjects the temporal organization of the aldosterone circadian sequences seems to be completely independent of renin-angiotensin control. PMID- 6248592 TI - The in situ determination of melting-solidification points of lipid inclusions in fixed cultured cells. AB - Melting-solidification points of microscopic lipid inclusions in fetal human kidney cultures were determined visually by gradual heating of formol-fixed cell monolayers while immersed in dilute aqueous solutions of Nile blue A. Intracellular lipid inclusions stained red when their melting point was reached and reverted to blue color at the solidification temperature. The melting solidification points of intracellular lipid inclusions in kidney cells were determined to fall within 19-25, 40-50, and 60-65 degrees C range. PMID- 6248593 TI - Pathogenesis of virus-induced osteopetrosis in the chicken. AB - Infection of chicken embryos with a nondefective avian leukosis virus MAV-2(0) induced bone hyperplasia and profound suppression of bursal and thymic lymphoid cell development within 2- to 3 weeks after hatching. A time-course study of infectivity during embryonal life showed a gradual loss of susceptibility between the 10th day of incubation and hatching. This finding suggests that an embryonal stem cell either before or early after seeding into the bone and primary lymphoid organs is a virus-susceptible target cell. Histologic observations of the bursa indicated only mild damage during the 1st week and severely impaired proliferation of follicular lymphoid cells during subsequent weeks of development. Thus, viral infection conferred a cytostatic rather than a cytolytic effect upon the lymphoid target cell. Infection of stem cells, which are progenitors of lymphoid cells as well as of bone osteoclasts, is compatible with the manifestations of the disease. A model of cellular disorders of the bone and lymphoid tissues is proposed. Adoptive transfer of lymphoid cells from adult MAV 2(0)-immunized chickens into histocompatible virus-infected juvenile recipients abrogated the manifestation of osteopetrosis. Passive injection of antiserum containing virus-neutralizing antibodies was also effective. Anti-gp85 viral surface glycoprotein-binding antibodies in sera from adoptively protected chickens receiving immune cells were exclusively of cell donor IgG allotype. PMID- 6248594 TI - Age-dependency of lymphocyte ecto-5'-nucleotidase activity. AB - The activity of lymphocyte ecto-5'-nucleotidase (ecto-5'-NT) decreases with advancing age, T lymphocyte ecto-5'-NT activity begins to fall after the age of 40 and subjects in the 41 to 50, 51 to 60, 61 to 75, and 75 to 85 age ranges of life have 57, 52, 38, and 19%, respectively, of the T lymphocyte ecto-5'-NT activity of subjects under the age of 40. TG cells (suppressor cells) have 39% of the ecto-5'-NT activity of Tnon-G cells (helper cells) but the increase in numbers of TG cells that occurs with age explains only about 14% of the age related fall in T lymphocyte ecto-5'-NT activity. B lymphocyte ecto-5'-NT activity remains stable until age 60 and subjects over 60 years of age have 42% of the B lymphocyte ecto-5'-NT activity of subjects under age 60. PMID- 6248595 TI - Early steps in specific tumor cell lysis by sensitized mouse T lymphocytes. IV. Inhibition of programming for lysis by pharmacologic agents. PMID- 6248596 TI - Establishment of immunologic memory concurrent with suppression of the primary immune response during acute cytomegalovirus infection of mice. PMID- 6248597 TI - Regulation by Fc fragments of the secretion of collagenase, PGE2, and lysozyme by mouse peritoneal macrophages. AB - Fc fragments of human IgG can stimulate resident mouse macrophages in culture to secret collagenase, to increase PGE2 secretion, and to decrease the secretion of lysozyme. Active synthesis and secretion were shown by the progressive accumulation of these products in the extracellular medium and inhibition of secretion by cycloheximide. A dose-dependent effect of Fc fragments was demonstrable. Brief exposure of cells to Fc fragments was sufficient to cause the macrophages to secrete collagenase and large amounts of PGE2 for prolonged periods of time, suggesting that a sustained activation rather than temporary modulation of the cells had occurred. Con A had similar effects on macrophage secretory activity. These findings indicate that proteins that bind to specific macrophage plasma membrane receptors may stimulate the secretion of products that promote the inflammatory response. PMID- 6248598 TI - Antibody responses to Epstein-Barr virus in families with the X-linked lymphoproliferative syndrome. PMID- 6248599 TI - Behavior of pigment cells. PMID- 6248600 TI - Disease due to enterotoxigenic Escherichia coli in Bangladeshi adults: clinical aspects and a controlled trial of tetracycline. AB - The clinical characteristics of disease due to enterotoxigenic Escherichia coli (ETEC) were determined in 88 adult males admitted to a hospital in Dacca, Bangladesh, with moderate to severe dehydration. Persons infected with ETEC strains producing both heat-labile toxin (LT) and heat-stable (ST) toxin had more dehydration and acidosis, longer duration of illness, and greater stool volume than persons infected with strains producing only ST. Tetracycline therapy, evaluated in 63 cases, resulted in slightly earlier termination of illness in patients with LT-ST strains but had no effect on illness in the patients with ST strains. In both groups of patients tetracycline shortened the duration of excretion of organisms. Because of its limited effectiveness and the generally excellent response of ETEC diarrhea to rehydration therapy alone, tetracycline is not warranted for use in treatment of ETEC diarrhea in adults in this population. PMID- 6248601 TI - Transplacental infection with Japanese encephalitis virus. AB - During a widespread epidemic of Japanese encephalitis, five pregnant women affected by the illness were observed. The diagnosis of Japanese encephalitis virus (JEV) infection was established on the basis of clinical presentation, rising titers of hemagglutination-inhibiting antibody, and the presence of specific IgM antibodies. Two women aborted, two were delivered of apparently normal children, and the fate of one case is not known. From brain, liver, and placental tissues of one of the aborted fetuses, JEV was isolated. This appears to be the first report of human transplacental infection with JEV. PMID- 6248602 TI - Lymphocyte reactivity in infectious mononucleosis. AB - Reactivity of lymphocytes to a purified preparation of Epstein-Barr virus (EBV) was studied in 17 healthy individuals and 15 patients with primary EVB infection and clinical signs of infectious mononucleosis. Lymphocyte reactivity to EBV was negative in individuals who were seronegative for antibody to EBV and in seven of 15 patients examined less than or equal to 21 days after onset of clinical signs of illness. Positive lymphocyte reactivity was observed in all patients by day 36; once it was established, it remained in individual patients for up to 480 days. During the acute phase of infectious mononucleosis, negative lymphocyte reactivity was always associated with a strong antibody response to EBV capsid antigens. This disparity was paralleled by the inability of lymphocytes to respond to recall antigens and mitogens, especially concanavalin A. Positive lymphocyte reactivity to EBV indicates a specific cellular memory function, probably of thymus-cell origin, which is acquired following primary EBV infection, and may be retained into later life. PMID- 6248603 TI - Cytomegalovirus infection in guinea pigs. IV. Maternal infection at different stages of gestation. AB - The effects of maternal infections with guinea pig cytomegalovirus (CMV) at different stages of gestation were evaluated in mothers, fetuses, and newborn animals. Increased cervical excretion of guinea pig CMV was detected in pregnant animals one to 30 days after inoculation. Fetal infection occurred in utero regardless of the time of maternal infection. The frequencies of stillbirths and viral infection in newborn offspring were higher in mothers infected in late gestation than in mothers infected during the first trimester of pregnancy. The major factor affecting isolation of guinea pig CMV from offspring was the duration of maternal infection. Virus was detected most often in fetuses and newborn animals within two weeks after inoculation of the mothers. Thereafter, guinea pig CMV disappeared progressively in the progeny, although histological lesions were observed and virus was found in the salivary glands of some offspring for as long as 14 weeks after delivery. PMID- 6248604 TI - [Frequent hypoglycemia induced by growth hormone (GH) and adrenocorticotropic hormone (ACTH) deficiency in chronic renal failure (author's transl)]. PMID- 6248605 TI - Vasopressin-prostaglandin interactions in isolated tubules from rat outer medulla. AB - Interactions between AVP and prostaglandins were investigated in MAL and MCT microdissected from the rat outer medulla. Incubation of MCT with 14C-arachidonic acid resulted in the formation of 14C-PGE2 and 14C-PGF2 alpha; however, when MAL was incubated under the same conditions, only traces of prostaglandins were formed. Prostaglandin synthesis in MCT was inhibited (-50%) by the prostaglandin cyclo-oxygenase inhibitor ibuprofen (10(-6)M). Preincubation with ibuprofen enhanced the stimulation of adenylate cyclase by 5 x 10(-9)M AVP in MCT but, in contrast, decreased the stimulation of adenylate cyclase by AVP in MAL. The effects of a second PG cyclo-oxygenase inhibitor naproxen (10(-5)M) were similar to those of ibuprofen. Ibuprofen did not influence cAMP phosphodiesterase activity in MCT or in MAL. Exogenous PGE2 or PGF2 alpha (10(-6)M) had no effect on either basal or AVP-stimulated adenylate cyclase activity in MCT. The present results demonstrated that MCT but not MAL is a site of active synthesis and accumulation of prostaglandin. Although both MAL and MCT have AVP-sensitive adenylate cyclase, incubation with prostaglandin cyclo-oxygenase inhibitors have, in the presence of arachidonic acid, an opposite effect on this enzyme in these two segments, resulting in increased AVP stimulation in MCT and decreased stimulation in MAL. Results also suggest that products of prostaglandin synthesis from arachidonic acid inhibit AVP-sensitive adenylate cyclase activity in MCT but not that located in MAL. Although not totally excluding the primary prostaglandins (PGE2, PGF2 alpha), these observations suggest that they are not responsible for AVP modulation in MCT. PMID- 6248606 TI - Demonstration of beta-2 adrenergic receptors of high coupling efficiency in human neutrophil sonicates. AB - Using highly purified (greater than 95%) neutrophil (PMN) sonicates, we have studied the beta adrenergic (beta 1/beta 2) pattern of adenylate cyclase activation following agonist stimulation and have assessed the coupling characteristics of the beta adrenergic receptor to the adenylate cyclase enzyme. Adenylate cyclase was highly responsive to agonist activation, with peak isoproterenol (100 microM) stimulation resulting in the generation of 119 +/- 9.5 (mean +/- S.E.M.) pmol/mg/min cyclic AMP (224% above basal levels) compared to 171.7 +/- 8.6 following NaF (10 mM) stimulation. The agonist pattern of adenylate cyclase activation suggested the presence of beta-2 adrenergic receptors, since isoproterenol with a Kact of 0.7 microM was more potent than epinephrine (Kact = 8.5 microM) or norepinephrine (Kact = 90 microM). Butoxamine (beta-2 antagonist) was approximately 25 times more potent than practolol (beta-1 antagonist), with KDs of 0.75 microM and 17.5 microM, respectively. Receptor coupling efficiency was determined by measuring isoproterenol binding and adenylate cyclase activation with the same PMN sonicates and incubation conditions for each assay. The apparent KD for isoproterenol binding was 2.82 +/- 0.53 muM, the Kact was 0.47 +/- 0.05 muM, and the mean KD/Kact ratio was 6.5. Highly coupled receptor enzyme systems have ratios greater than or equal to 1. Using sucrose gradient purified PMN sonicates, we found that isoproterenol required the guanine nucleotides GTP or Gpp(NH)p to activate adenylate cyclase. The GTP effect on adenylate cyclase responsivenss to isoproterenol was associated with a 10-fold decrease in the isoproterenol binding affinity. These studies suggest that the human PMN has beta-2 adrenergic receptors which are highly coupled to the adenylate cyclase enzyme. We believe that this tissue offers a suitable model for the study of beta-2 adrenergic receptors and the mechanism of hormone-induced adenylate cyclase activation in man. PMID- 6248607 TI - Phosphate accumulation by the isolated renal tubule and the effects of parathyroid hormone and cyclic adenosine monophosphate. AB - The effects of metabolic and transport inhibitors and PTH, cAMP, db-cAMP, and theophylline on Pi uptake by an isolated rat renal tubular preparation has been investigated. Pi uptake by this preparation was a saturable process, was O2- and sodium-dependent, was inactivated by heat=treatment, and was inhibited by dinitrophenol. iodacetate, ouabain, and a decrease in temperature from 37 degrees to 4 degrees C. PTH and cAMP stimulated Pi uptake by energy-dependent and ouabain inhibitable mechanisms. PMID- 6248608 TI - Adenylate cyclase in leukocytes from patients with cystic fibrosis. AB - Lymphocytes from patients with cystic fibrosis produce significantly less cAMP in response to beta-adrenergic stimulation than do cells from healthy persons (p less than 0.0005) or patients with bronchiectasis (p less than 0.005). Adenylate cyclase in the basal state or stimulated by GMPPNP or PGE1 is normal, but isoproterenol-stimulated adenylate cyclase activity is significantly (p less than 0.005) reduced in lymphocyte membrane preparations from patients with cystic fibrosis. Granulocytes from patients with cystic fibrosis also produce significantly less cAMP in response to beta-adrenergic stimulation than do cells from healthy subjects (p less than 0.0005) or subjects with bronchiectasis (p less than 0.05). Adenylate cyclase activity in granulocyte homogenates from patients with cystic fibrosis is normal in the basal state or when stimulated by GMPPNP or PGE1 but is significantly (p less than 0.05) reduced compared to normal when stimulated by isoproterenol. These data suggest that the defect is not related to adenylate cyclase itself or to availability of substrate or cofactor to adenylate cyclase, and they may be indicative of a more generalized membrane defect in cystic fibrosis. PMID- 6248609 TI - Empyema caused by Clostridium perfrigens. PMID- 6248611 TI - Hepatocellular carcinoma and cirrhosis in Thailand: etiologic considerations of underlying cirrhosis. PMID- 6248610 TI - The importance of angiography in tumours of the head and neck. AB - Reference is made to five cases appearing as expansive lesions in the head and neck. In all cases angiography allowed a precise diagnosis of the nature and extent of the lesion. Biopsy which could have been hazardous was thus unnecessary. Moreover, therapeutic embolization in a case of juvenile nasopharyngeal angiofibroma prevented massive bleeding during surgery. PMID- 6248612 TI - Iodination of thyroid-stimulating hormone for receptor-binding studies with human thyroid membranes: effects of specific activity and method of iodination. AB - Three different methods were compared for 125I-labelling of thyroid-stimulating hormone (TSH) for use in receptor-binding studies with human thyroid membranes: these were the chloramine-T, Bolton-Hunter and lactoperoxidase methods. Chloramine-T proved to be an inferior method to the other two. Iodinations to different specific activity (0.7--9.4 Bq/pg) were also compared: too high a specific activity led to reduced binding and a dramatic shift in the pH optimum for the TSH-receptor interaction. A specific acitivity of 2.5 Bq/pg should not be exceeded if binding of 125I-labelled TSH is to be representative of the binding of the natural hormone. Under these conditions, pH 7.5 was optimal for binding of TSH to its receptor. Repurification of the labelled TSH by receptor adsorption also proved to be essential. PMID- 6248613 TI - Mechanisms of catabolism of corticotrophin-(1--24)-tetracosapeptide in the rat in vivo. AB - The fragmentation of corticotrophin-(1--24)-tetracosapeptide in vivo has been studied, using tritium-labelled hormone and chromatography, in the rat. After intravenous injection the levels of peptide in the circulation declined rapidly caused by its distribution to the tissues and from 2 min after injection a range of different cleavage products appeared. Many of the fragments in the circulation after 2 min have been identified and in this way cleavage has been shown to occur after residues 1, 2, 8, 15, 16, 17, 19, 20 and 21. It is believed that this is the result of aminopeptidase attack at the NH2 terminal, and of attack on the basic region of the molecule by trypsin-like endopeptidase followed by carboxypeptidase. The sulphoxide has been identified as a major metabolite in some experiments but the extent of its formation was very variable. Seventy per cent of the dose was distributed to the tissue beds by 1 min. Part of this was present, mainly as intact peptide, in liver and kidney but the greater proportion was found in muscle, skin and intestine where extensive degradation had already occurred. Further characterization of the fragments formed in the muscle provided good evidence that this tissue may have been the site of generation of many of the fragments which later appeared in the circulation. PMID- 6248614 TI - Steroids, fiber and related factors in carcinogenesis. PMID- 6248615 TI - A comparison of lipstick smears by high performance liquid chromatography. PMID- 6248616 TI - Insulinoma: a clinical study of 18 cases. PMID- 6248617 TI - Recurrent Cushing's syndrome after bilateral total adrenalectomy. PMID- 6248618 TI - Effects of barium on the potassium conductance of squid axon. AB - Ba++ ion blocks K+ conductance at concentrations in the nanomolar range. This blockage is time and voltage dependent. From the time dependence it is possible to determine the forward and reverse rate constants for what appears to be an essentially first-order process of Ba++ interaction. The voltage dependence of the rate constants and the dissociation constants place the site of interaction near the middle of the membrane field. Comparison of the efficacy of Ba++ block at various internal K+ concentrations suggests that Ba++ is probably a simple competitive inhibitor of K+ interaction with the K+ conductance. The character of Ba++ block in high external K+ solutions suggests that Ba++ ion may be "knocked off" the site by inward movement of external K+. Examination of the effects of other divalent cations suggests that the channel may have a closed state with a divalent cation inside the channel. The relative blockage at different temperatures implies a strong interaction between Ba++ and the K+ conductance. PMID- 6248619 TI - Adenine + thymine content of different genes located on the broad host range plasmid RP4. AB - The genetic map of plasmid RP4 was correlated with its adenine+thymine (AT) map. For this purpose, RP4 DNA was digested with one or both of the restriction enzymes EcoRI and HindIII and the resulting linear RP4 molecules and fragments were partially denatured, examined in the electron microscope and their AT maps were determined using a computer program. From these AT maps the EcoRI and HindIII restriction sites were located on the AT map of RP4. Since the positions of these restriction sites on the genetic map of RP4 are known, the maps could be compared. They revealed a high AT content for the Tn1 transposon and the kanamycin resistance gene. The tra-1 region is also distinguished by a sharply defined AT-rich region, whereas tra-2 and the tetracycline resistance gene have an AT content which is not distinctly different from the average AT content of RP4. PMID- 6248620 TI - Transposition of Tn951 (Tnlac) and cointegrate formation are thermosensitive processes. AB - The frequency of transposition of Tnlac to pGC200, an IncFII R plasmid, increased during the storage of the host strain. This result is explained by the fact that the transpositional event is temperature-dependent: it occurred readily when the host strain was grown at 30 degrees C but it was nearly undetectable when the host strain was grown and kept at 37 degrees C. Fusions between two different plasmids carrying Tnlac with pGC200 were also thermosensitive, suggesting a relation between cointegrate formation and transposition. Lactose did not influence the frequency of transposition of Tnlac. PMID- 6248621 TI - Quantitative gallium-67 scanning for predictive value in primary lung carcinoma. AB - Gallium-67 scintigraphy was performed on 87 patients with a variety of histological types of untreated primary lung carcinoma. Gallium-67 uptake was determined, allowing for differences in tumor size. Differential uptakes were found for the various tumor types, with anaplastic small-cell carcinoma having the greatest average uptake, and adenocarcinoma and anaplastic large-cell carcinoma the smallest. Gallium-67 uptake was compared with response to radiation therapy, incidence of metastasis, and host survival in 58 of the patients. From these results it is suggested that the greater the Ga-67 accumulation in the tumor, the more effective is radiation therapy in reducing tumor size. Gallium-67 scintigraphy appears to be a valuable tool in estimating the sensitivity of the tumor before radiation therapy and in indicating the prognosis following radiation therapy in patients with primary lung carcinoma. PMID- 6248622 TI - [Facial paralysis and varicella-zoster virus (VZV): serum antibody titer and VZV skin test (author's transl)]. PMID- 6248623 TI - Respiratory metabolism of Giardia lamblia. PMID- 6248625 TI - Determination of potential content of vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol) in gelatin-coated beadlets, oil-based mixtures, and multivitamin tablet and capsule formulations. AB - A high-performance liquid chromatographic procedure was used to determine routinely the potential vitamin D content in raw materials and multivitamin formulations. The method employs a microparticulate silica column to separate vitamin D from its degradation products as well as other fat-soluble vitamins. Sample preparation is simple, and the chromatographic time is less than 20 min when progesterone is added to the injection mixture as an internal standard. Replicate analyses of complex multivitamin formulations demonstrate precision with a relative standard deviation of less than 4%. Spiked placebos typically show 98--100% recovery and a linear chromatographic response. The use of bulk drug as a working reference standard is recommended for the determination of the potential vitamin D concentration in pharmaceutical multivitamin preparations. PMID- 6248624 TI - [Opiate receptors, endogenous peptides and analgesia (author's transl)]. PMID- 6248626 TI - HgCl2 inhibition of D-glucose transport in jejunal tissue from 2 day and 21 day chicks. AB - Chick jejunal slices that were exposed to HgCl2 exhibited markedly reduced uptakes of D-glucose. The carrier-mediated (phloridzin inhibitable), but not diffusive, component of uptake was affected by Hg. Within each age group, I50 values (concentration of HgCl2 causing 50% inhibition of mediated transport) for slices (mucosal plus serosal exposure) and sacs (mucosal exposure only) were nearly identical; values for brush border membrane vesicles were slightly lower (increased sensitivity). For each preparation, I50 values for 2 day chicks were consistently lower than corresponding values for 21 day chicks. Taken together, these data indicate that the jejunal brush border membrane is a site of HgCl2 action and that membrane sites in tissue from 2 day chicks are more sensitive to Hg than similar sites in tissue from 21 day chicks. PMID- 6248627 TI - Possible role of an endogenous opiate in the cardiovascular effects of central alpha adrenoceptor stimulation in spontaneously hypertensive rats. AB - In unanesthetized sponatneously hypertensive rats (SHR), naloxone (0.5--2 mg/kg ip.) or naltrexone (2 mg/kg) inhibited the hypotension and bradycardia produced by clonidine (5--20 micrograms/kg iv.). Chronic treatment of SHR with clonidine (3 x 20 micrograms/kg/day orally for 12 days) reduced blood pressure and heart rate and these effects were acutely reversed by a single injection of naloxone. Naloxone also reversed the hypotension produced by a single injection of alpha methyldopa (50--300 mg/kg ip.). In pentobarbital-anesthetized SHR, the hypotension and bradycardia produced by 5 micrograms/kg of clonidine were inhibited either by naloxone (2 mg/kg) or by yohimbine (1 mg/kg ip.). Morphine (0.33 mg/kg iv.) also reduced blood pressure and heart rate in these animals but these effects were only antagonized by naloxone and not by yohimbine. In conscious and anesthetized normotensive Wistar Kyoto rats, the reduction in blood pressure and heart rate by clonidine or alpha-methyldopa were smaller than in SHR, and these effects were not influenced by naloxone. These results confirm and extend earlier observations and suggest the existence of an "opioidergic" component in the antihypertensive action of central alpha adrenoceptor stimulants in SHR. They also show that a similar mechanism is either absent or inactive in the normotensive Wistar Kyoto rats. PMID- 6248628 TI - Effects of acetaldehyde upon mechanical properties of isolated rat papillary muscle. AB - The acute effects of acetaldehyde upon the performance of isolated rat papillary muscle were studied. At high concentrations (50 and 100 mg/100 ml), acetaldehyde demonstrated a negative inotropic effect and abbreviated relaxation time. Pretreatment with either propranolol or reserpine unmasked a direct negative inotropic effect of acetaldehyde at concentrations as low as 5 mg/100 ml. The shortening of relaxation was also blocked by propranolol and reserpine. These findings are compatible with both a direct myocardial depressant effect and an indirect beta-stimulatory effect of acetaldehyde. In the range of concentrations encountered clinically, however, acetaldehyde is not likely to have a significant acute effect upon cardiac muscle performance. PMID- 6248629 TI - Role of extracellular Ca++ in regulating isoproterenol-stimulated phosphorylase a formation in murine skeletal muscle. PMID- 6248630 TI - Effects of clofibrate on water permeability and short-cicuit current of toad urinary bladder. AB - The effects of the oral antidiuretic drug clofibrate on water permeability of the urinary bladder of the toad, Bufo marinus, were studied. Clofibrate did not alter control water flow along an osmotic gradient. Water flow increases due to vasopressin were reversibly inhibited by 1 to 10 mM clofibrate from the serosal side. Clofibrate in the serosal bathing medium inhibited water flow increases due to cyclic AMP but not due to theophylline. Serosal clofibrate concentrations less than 1 mM or clofibrate in the mucosal solution (1 mM) was ineffective in inhibiting the osmotic water permeability response to vasopressin. Clofibrate in the serosal bathing medium (1 mM) inhibited base-line short-circuit current but had no effect on vasopressin-stimulated short-circuit current. PMID- 6248631 TI - Studies on the reduction of sputum viscosity in cystic fibrosis using an orally absorbed protected thiol. AB - The viscosity of cystic fibrosis fluids leads to clinical difficulties in adequate clearance of the respiratory and gastrointestinal tracts and in delivery of gases and nutrients to their respective sites. Various sulfhydryl agents are effective in reducing in vitro sputum viscosity. Present therapy for cystic fibrosis involves the aerosolization of N-acetylcysteine, presenting problems of toxicity and inadequate delivery to the small airways. We have been assessing various prodrugs which would liberate the free thiol in vivo and which would be orally absorbed. The free thiol of WR 2721, at a concentration of 1 mM, reduces sputum viscosity by 70% in 15 min. WR 2721 is hydrolyzed to the free thiol chemically at an acid pH and enzymatically by homogenates of the liver and gut. It is well absorbed (23%) after oral administration to rabbits. Clinical studies indicate that orally administered WR 2721 is without toxicity and reduces sputum viscosity in cystic fibrosis patients in 30 to 60 min after administration. PMID- 6248632 TI - The effect of phospholipase C on the responsiveness of cardiac receptors. II. The specificity of phospholipase C inhibition of receptor-mediated responses. PMID- 6248633 TI - beta-Endorphin: central sites of analgesia, catalepsy and body temperature changes in rats. AB - beta-Endorphin was microinjected into rat brain in order to localize central sites associated with some of its pharmacologic effects: namely, analgesia (inhibition of the tail-flick response), catalepsy and changes in body temperature. Microinjections (1 microliter) were made bilaterally under halothane anesthesia and the effects of beta-endorphin were repeatedly assessed at 15- or 30-min intervals for 2 hr. beta-Endorphin produced analgesia and catalepsy when it was injected at low doses (ED50, 1.3 to 2.7 micrograms) into the medial preoptic area, nucleus accumbens, anterior hypothalamus and the periaqueductal gray-4th ventricular spaces. Brain areas of intermediate sensitivities (ED50, 3.7 to 16 micrograms) were the medial thalamus, posterior hypothalamus and areas around the fasciculus retroflexus. The frontal cortex, striatum and lateral areas of the brain were relatively insensitive (ED50 greater than 17 micrograms) to the effects of beta-endorphin on analgesia and catalepsy. beta-Endorphin had complex effects on body temperature. For example, when beta-endorphin was injected into the nucleus accumbens or preoptic area, low doses (1.1--2.1 micrograms) produced hyperthermia; higher doses (8.5 micrograms) produced hypothermia. The brain regions in which low doses of beta-endorphin elicit pharmacologic effects correspond to the anatomic areas in which the endogenous beta-endorphin system is distributed. Similar correspondence to the endogenous enkephalin system was not obtained. PMID- 6248634 TI - Inotropic actions of doxorubicin in isolated guinea-pig atria: evidence for lack of involvement of Na+,K+-adenosine triphosphatase. PMID- 6248636 TI - Who supports the support system? PMID- 6248635 TI - Opioid binding properties of brain and peripheral tissues: evidence for heterogeneity in opioid ligand binding sites. PMID- 6248637 TI - Sex-typing and consumer preference for a male or female psychotherapist. PMID- 6248638 TI - Causal attributions: bias in the nurse-patient relationship. AB - The study relates the social psychological concept of attribution to professional nursing practice. Namely, dispositional vs. situational causal attribution as affected by position (nurse/patient) and role (actor/observer) and its impact on the therapeutic relationship. Contrary to most studies in this field this one moves out of the laboratory and tests actual psychiatric patients and correspondent nursing staff. Twenty nurses and twenty patients responded to statements representing situational and dispositional causal attributions about 22 behaviors of nurses and 22 behaviors of patients. Both patients and nurses tended to attribute the behavior of patients to causes inherent in their personality more often than to external factors. Nurses also tended to give more internal causation to their own behavior while patients gave equal numbers of external and internal causes to nurses' behavior. The findings which support an information processing approach to understanding perceptions are discussed as to their implications for the nurse-patient relationship. PMID- 6248639 TI - Nursing assessment of mental disorders on a general medical unit. PMID- 6248640 TI - Lung defenses in neonates: effects of bronchial lavage fluids from adult and neonatal rabbits on superoxide production by their alveolar macrophages. PMID- 6248641 TI - Effects of benoxaprofen and indomethacin on platelet function and biochemistry. AB - Benoxaprofen did not impair platelet function or platelet prostaglandin synthesis in vivo or in vitro in contrast to indomethacin, a known prostaglandin synthesis inhibitor. Platelet cyclic AMP levels were not changed by either drug in vivo or in vitro. The results of routine tests for hemostatic function (template bleeding time and blood clotting assays) were not changed by either drug. A trend towards inhibition of cAMP-dependent protein kinase by benoxaprofen was observed. The significance of this observation, if valid, remains obscure. These studies suggest that benoxaprofen, which does not appreciably suppress hemostatic function, may be used safely in patients with acquired or congenital coagulation defects (e.g. patients receiving oral anticoagulant, hemophiliacs with arthropathy). PMID- 6248642 TI - Mammalian alkaloids. 8. Synthesis and biological effects of tetrahydropapaveroline related 1-benzyltetrahydroisoquinolines. PMID- 6248643 TI - Oxime and dithiolane derivatives of 5-formyl-2'-deoxyuridine and their 5' phosphates: antiviral effects and thymidylate synthetase inhibition. AB - 5-Formyl-2'-deoxyuridine (2a), an effective inhibitor of herpes simplex virus type 1 or 2 (HSV-1, HSV-2) and vaccinia virus, was converted to the oxime (3a) and dithiolane (4a) derivatives. The oxime (3a) was equally as potent as the formyl compound against HSV-1, but one-fifth as active against HSV-2, 100 times less effective against vaccinia, and 25 times less toxic for the host cells. In addition, compound 3a was about 10 times less active than 2a in inhibiting thymidylate synthetase in vivo (as reflected by a differential inhibition of dThd and dUrd incorporation into host cell DNA). The dithiolane (4a) did not exert an appreciable effect on either virus multiplication or dThd or dUrd incorporation, nor was it cytotoxic. All these compounds as their 5'-phosphate derivatives were potent in vitro inhibitors of thymidylate synthetase (Lactobacillus casei). The inhibition was competitive with substrate with Ki/Km ratios of 0.05 for the formyl 2b, 0.5 for the oxime 3b, and 0.2 for the dithiolane 4b. Thus, 3b was 10 times less active than 2b as an in vitro inhibitor of thymidylate synthetase, which appears to corroborate the in vivo findings. PMID- 6248644 TI - Some spiro analogues of the potent analgesic ketobemidone. AB - A series of spiro analogues of the potent narcotic ketobemidone have been prepared and found to be devoid of opiate activity. Additional pharmacology and possible implications for the mode of binding of ketobemidone to the analgesic receptor are discussed. PMID- 6248645 TI - 14-(Arylhydroxyamino)codeinones and derivatives as analgetics and antagonists. AB - Diels-Alder reaction of thebaine (1) and N-(cyclopropylmethyl)northebaine with nitrosobenzene and p-fluoronitrosobenzene gave adducts [6,14-exo (phenyloxyamino)codeine 6-methyl esther and derivatives, 2a-d] which yielded 14 (phenylhydroxyamino)codeinone and derivatives (3a-d) on acid hydrolysis. Rearrangement of 3 (NaOMe) afforded 5,14-exo-(phenyloxyamino)thebainone and derivatives (4a-d); reduction of 3 led to 14-(phenylamino)dihydrocodeinone and derivatives (5a-d). Thebaine also reacted with 1-halo-1-nitrosocyclohexane (halo = Cl, Br) and with benzohydroxamic acid under oxidizing conditions to give 14 (hydroxyamino)codeinone (6). All compounds, 3-6, were evaluated as analgetics and antagonists by the tail-flick, writhing, and Straub tail assays: compounds of types 3-5 were analgetics (N-Me), one-third to one-tenth as potent as morphine, or antagonists [N-(cyclopropylmethyl)], 50 to 100 times less potent than naloxone; 6 behaved as an antagonist in the tail-flick test but as an agonist in the other assays. Opiate receptor binding studies indicate that compounds of type 3 may be useful as opiate spin-label precursors. PMID- 6248646 TI - Allosteric inhibition of the Ca2+-activated hydrophilic channel of the mitochondrial inner membrane by nucleotides. AB - The control by nucleotides of the Ca2+ -activated channel which regulates the nonspecific permeability of the mitochondrial inner membrane has been investigated quantitatively. The cooperative binding of two molecules of ADP to the internal (matrix) side of the channel causes a mixed-type inhibition of channel activity. ATP, AMP, cAMP and GDP are all ineffective. NADH shows a pattern of inhibition similar to that of ADP, though the apparent KI is higher by a factor of 200. NADPH relieves the inhibition by NADH. NAD+ also inhibits, b,t its affinity is a factor of 10 less than that of NADH. When ADP and NADH are added together, they act synergistically to inhibit the Ca2+-activated channel. It is concluded that the concept of the modification of enzyme activity by the allosteric binding of nucleotides, which is well established for soluble enzyme systems, also has application to the regulation of channels that control membrane permeability. PMID- 6248647 TI - Extrahepatic bile duct obstruction in primary carcinoma of the lung: incidence, diagnosis, and non-operative treatment. AB - Jaundice associated with primary carcinoma of the lung was identified in 19 patients from 1973-1978. Eight of these patients had demonstration of extrahepatic bile duct obstruction (EHBDO). The most frequent histologic type of lung tumor was undifferentiated, occurring in six of the eight patients with proved EHBDO. The EHBDO resulted from metastatic involvement in peripancreatic, periportal, and peribiliary lymph nodes. Metastasis to the common bile duct was rare. However, metastases to the head of the pancreas were a frequent event, being found in six of the eight patients with EHBDO. Discussion of diagnosis and recommendations for treatment are included. PMID- 6248648 TI - Cannabinoid-induced hormone changes in monkeys and rats. AB - Previous findings at various laboratories indicated that cannabinoids distribute to sexual behavior centers in the brain, and endocrine aberrations have consistently been observed in animals treated with cannabis constituents. Subacute and chronic studies were performed to monitor hormone changes in rats and monkeys exposed to marihuana smoke or pure cannabinoids. In oral studies, young Fischer rats of both sexes were given delta 9-tetrahydrocannabinol (delta 9 THC) doses of 2, 10, or 50 mg/kg for 14--180 d and pregnant rats received 1, 5 or 10 mg/kg during gestation and lactation. Other male rats were exposed to marihuana smoke at delta 9-THC doses of 2 or 4 mg/kg for 14 d. Rhesus monkeys of either sex were given oral cannabidiol doses of 30, 100, and 300 mg/kg for 90 d. Serum pituitary, steroid, and thyroid hormone levels were determined by radioimmunoassay. Marihuana smoke (and oral delta 9-THC) depressed testosterone 20--30% and triiodothyronine 17--29%. In pregnant rats, small doses of delta 9 THC suppressed luteinizing hormone, but larger doses elevated both follicle stimulating hormone and estrogens (approximately 50--100%) without affecting progesterone levels. Prolonged oral administration of delta 9-THC to young rats tended to increase gonadotropins, to which tolerance developed in males. Cannabidiol-treated monkeys responded with slight elevations in luteinizing hormone and follicle-stimulating hormone in males, whereas steroid hormones were essentially unchanged for both sexes. Hormone imbalance may explain cannabinoid induced embryotoxicity and impaired gonadal function. PMID- 6248649 TI - Estimating the hazards of "less hazardous" cigarettes. I. Tar, nicotine, carbon monoxide, acrolein, hydrogen cyanide, and total aldehyde deliveries of Canadian cigarettes. AB - The tar, nicotine, CO, HCN, total aldehyde, and acrolein deliveries of 102 brands of Canadian cigarettes have been determined. On the basis of these deliveries, 15 brands (9% of sales) were categorized as low hazard and 9 brands (10% of sales) as high hazards. All six constituents were used for the classification since for most brands tar was a poor indicator of gas-phase deliveries. As a result, smokers who indiscriminately switch to a brand with a lower tar delivery may inadvertently increase their exposure to gas-phase constituents such as CO and increase their risk of smoking-related pathology. With respect to Canadian cigarettes, the choice of a 30-mm standard butt length may result in omission of some of the available tobacco from the testing procedure, thus reducing the value of tar level as a guide to choosing a less harmful cigarette. PMID- 6248651 TI - FDA ponders wider distribution of THC. PMID- 6248650 TI - Noncontraceptive estrogens and myocardial infarction in young women. AB - The effect of noncontraceptive estrogens on the risk of myocardial infarction (MI) in women aged 30 to 49 years was investigated in 477 women with first infarctions and in 1,832 hospital control subjects. There was little evidence of an effect: overall, the estimated relative risk of acute MI for women who had used noncontraceptive estrogens in the preceding month, after allowance for potential confounding factors, was 1.0 (95% confidence intervals, 0.6 to 1.7); the corresponding estimate for women who had discontinued use more than one month previously was 1.2 (0.8 to 1.8). There was also no apparent association in various subgroups, including women who smoked heavily and those who had no identified predisposition. PMID- 6248652 TI - Sino-orbital aspergillosis treated with combination antifungal therapy. Successful therapy after failure with amphotericin B and surgery. PMID- 6248653 TI - Malignant fibrous histiocytoma of the heart. AB - A 33-year-old woman presented signs and symptoms which suggested mitral stenosis and insufficiency. Subsequent echocardiographic and angiographic testing demonstrated a left atrial tumor which was suspected clinically to be a left atrial myxoma. At surgery, the tumor was partially resected and histological examination revealed that the mass to be a malignant fibrous histiocytoma. At autopsy, the tumor was found to be localized in the heart, and there was no metastasis. PMID- 6248654 TI - Effect of sodium loading and depletion on vascular reactivity and prostacyclin generation. AB - In order to estimate the modulatory activity of Prostacyclin (PGI2) to the vascular reactivity, pressor responses to angiotensin II (A II) and noradrenaline (NA) and PGI2 generation aorta were measured using the rats of sodium loading or of sodium depletion. On the sodium loading, the blood pressure increased gradually and plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were decreased. The pressor responses to A II and NA were enhanced by sodium loading. The PGI2 generation of aorta was enhanced at the initial stage of sodium loading and decreased thereafter. The increased generation of PGI2 may represent the adaptive mechanism for the attenuation of the sustained elevation in blood pressure. It sodium depletion, the pressor responses to A II and NA were decreased, and PRA and PAC were elevated. PGI2 generation of aorta was also increased. These findings suggested that PGI2 could participate in blood pressure control mechanism on sodium loading and depletion. PMID- 6248655 TI - Distribution and role of angiotensin II receptor in the brain of spontaneously hypertensive rat. PMID- 6248656 TI - [Endocrinologic studies of tumors of Langerhans Islands]. PMID- 6248657 TI - [Regulation and secretogogues of pancreatic exocrine functions--with special reference to receptors, cGMP and cAMP]. PMID- 6248658 TI - [Argentinian hemorrhagic fever: epidemiology, symptomatology, management and prognosis]. PMID- 6248659 TI - [Bolivian hemorrhagic fever: epidemiology, symptomatology, management and prognosis]. PMID- 6248660 TI - [Problems with smallpox]. PMID- 6248661 TI - [Communicable diseases: international cooperation and present status of studies in various countries]. PMID- 6248662 TI - [Endocrine interrelationship between the pancreas and digestive system]. PMID- 6248663 TI - [Progress in the studies of the thyroid gland using cultured thyroid gland cells]. PMID- 6248664 TI - [Action mechanism of thyroid hormones]. PMID- 6248665 TI - [Immunological tests of the thyroid gland--their significance and limitations]. PMID- 6248666 TI - [Trends in the etiological studies of Graves' disease]. PMID- 6248667 TI - [Normal value, predictive value and panic value. Functional analysis of laboratory tests (author's transl)]. PMID- 6248668 TI - [Detection of hepatic neoplasms by computed tomography in portal hepatogram phase (author's transl)]. PMID- 6248669 TI - [Comparison of radionuclide scans and computed tomography of hepatoma (author's transl)]. PMID- 6248670 TI - [A case of mixed pulmonary infection with cytomegalovirus and Nocardia asteroides diagnosed by transbronchofiberscopic biopsy and tube aspiration (author's transl)]. PMID- 6248671 TI - Smoking and hepatitis B-negative primary hepatocellular carcinoma. AB - Smoking histories were obtained from 79 patients with primary hepatocellular carcinoma (PHC) (of whom 40 were negative and 39 positive for serum hepatitis B surface antigen), 39 patients with liver cancer not primary in the liver (LCNP), and 204 hospitalized controls. All subjects were Caucasians of Greek nationality and residence. No significant difference in smoking habits was found between controls and either PHC patients positive for serum hepatitis B surface antigen or LCNP patients. In contrast, there was a highly significant association between smoking and PHC negative for serum hepatitis B surface antigen (P less than 10( 4)); this association was not accounted for by the greater alcohol consumption of smokers. The risk ratios were 1.3, 2.5, 3.7, and 8.4 for current smokers of 1-10, 11-20, 21-30, and 30+ cigarettes per day. PMID- 6248672 TI - Effects of levamisole on pathogenesis of Marek's disease. AB - Levamisole was administered to chickens previously inoculated with Merek's disease virus (MDV) or infected by contact, and the influence of the drug on the mortality rate of Merek's disease (MD) was examined. The chickens inoculated with MDV and then administered levamisole (3 mg/bird) began to die earlier than chickens not treated with levamisole. However, the chickens infected with MDV by contact and then treated with the levamisole had delayed deaths. When the capacity of peritoneal exudate cells (PEC) to inhibit MDV plaque formation on chicken kidney cell (CKC) cultures was examined, the inhibitory activity of PEC from chickens inoculated with MDV and treated with levamisole at 4 days or 2 months of age was much weaker than that of PEC from chickens of the same ages that were not treated with levamisole. This effect was also noted when levamisole was added to CKC cultures to examine the inhibitory activity of PEC from MDV infected chickens not treated with levamisole. These results indicate that the administration of levamisole to MDV-inoculated chickens in doses used in the present experiment suppressed the macrophage restriction on MDV replication and hastened the death of chickens by MD during the early course of infection. PMID- 6248673 TI - Carcinogenicity and hepatotoxicity of cycasin and its aglycone methylazoxymethanol acetate in nonhuman primates. AB - The carcinogenic potential of cycasin and methylazoxymethanol (MAM) acetate was investigated in nonhuman primates. Old-world monkeys (rhesus, cynomolgus, and African green monkeys) received cycasin and/or MAM acetate by oral or ip routes up to 11 years. Eighteen monkeys survived longer than 2 months after initiation of treatment with cycasin (50-75 mg/kg) or MAM acetate (1.5-3.0 mg/kg) given orally 5 days/week; 9 of the animals were necropsied. Histopathologic examination of a liver tumor from 1 of these monkeys revealed well-differentiated hepatocellular carcinoma. A second monkey had multiple tumors, including hepatocellular carcinoma, intrahepatic bile duct adenocarcinoma, renal carcinoma and adenomas, and adenomatous polyps of the colon. Although liver tumors were not observed in the other monkeys, all but 1 monkey had hepatic lesions such as toxic hepatitis and cirrhosis. These monkeys had received cycasin and/or MAM acetate for an average of 57 months (range, 2-133 mo). A group of 10 monkeys received MAM acetate by weekly ip injections (3-10 mg/kg). Six of these animals developed tumors after receiving an average of 6.14 g (range, 3.58-9.66 g) of MAM acetate for an average of 75 months (range, 50-89 mo). Four of the monkeys developed hepatocellular carcinomas, and 2 had multiple primary tumors including hepatocellular carcinomas, renal carcinomas, squamous cell carcinomas of the esophagus, and adenocarcinomas of the small intestine. Our results showed that long-term administration of cycasin and/or MAM acetate by oral and ip routes was hepatotoxic and carcinogenic in old-world monkeys. PMID- 6248674 TI - Human placental and pituitary glycoprotein hormones and their subunits as tumor markers: a quantitative assessment. PMID- 6248675 TI - [Work efficiency of the sarcoplasmic reticulum of the heart under normal and pathological conditions]. AB - The problem concerning the participation of the sarcoplasmic reticulum in the relaxation of the heart muscle is discussed. It is concluded on the grounds of certain data that the system of the myocardial calcium pump includes several components, one of which, the Ca-dependent ATP-ase, is responsible for the accumulation of calcium ions while the others regulate this process accordingly. The results of an experiment with full extraction of the membrane Ca-transport system from the heart muscle are described, and the amount of sarcoplasmic reticulum in the pigeon myocardium is assessed. PMID- 6248676 TI - [Pyrophosphate-99mTc scintigraphy in stenocardia patients]. AB - The authors examined 166 patients with ischemic heart disease and attacks of angina pectoris and 21 healthy individuals. Scintigraphy, electrocardiography and tests for the activity of creatine phosphokinase and its MB fraction were carried out at rest, during physical exercise and 1--3 days after it. It was found that pyrophosphate-99mTc may accumulate in the myocardium both during the attack of angina pectoris and after its cessation. Angina pectoris may occur both with diffuse and with focal pyrophosphate-99mTc accumulation in the myocardium. Positive results of scintigraphy were encountered considerably more often in patients examined during physical exercise than in those examined at rest. Scintigraphic signs of angina pectoris which occurs under the effect of physical exertion develop less frequently, but persisted for a longer time than its electrocardiographic signs. PMID- 6248677 TI - [2 mechanisms of the "stimulus-dependent" action of pharmacological agents on the electrical and contractile activity of myocardial cells]. PMID- 6248678 TI - [Complex radioisotope and ultrasonic scanning in liver diseases]. PMID- 6248679 TI - [Surgical treatment of insuloma with a case of a successfully treated patient]. PMID- 6248680 TI - Viral hepatitis A and B in hemodialysed patients. AB - In 113 hemodialysed patients, 167 hospitalized patients, and 143 outpatients the frequency of HAV and HBV markers were studied by testing HBsAg, anti-HBs, anti HBc, HBeAg, anti-HBe, and anti-HAV. The hemodialysis patients in a dialysis center had significantly more often HBV markers (85.7%) than those maintained on home-dialysis (46.5%). 29.9% of the hospitalized patients and 32.1% of the outpatients had HBV markers. By the anti-HBc test up to 41% of additional HBV infections could be detected.--The prevalence of anti-HAV was very high in all groups. Significant differences between the hemodialysis patients and the control groups existed only in the age groups up to 39 years.--The frequencies of HAV and HBV markers were related to age, duration of dialysis treatment, transfusional frequency, and transaminases. The HBV appeared as the clinically important hepatitis agent in dialysis. PMID- 6248681 TI - [The place of attack of beta-2 receptor stimulating bronchodilators. Fenoterol (Berotec) in allergic airway obstruction in dogs, hypersensitive to Ascaris suum]. AB - On dogs sensitive against Ascaris suum extract an increase of the airway resistance can be caused by challenge alone on the upper part or the lower part of the airways by Ascaris suum extract. Fenoterol as beta 2-receptor stimulator is capable to decrease this reaction by deposition of this drug on the upper part as on the lower part of the airways. The effect of Fenoterol on the upper part of the airways is much stronger and lasts much longer than on the lower part of the airways or by intravenous route. A direct effect of the beta 2-receptor stimulator Fenoterol on the sensoric part of the reflex way of the reflex bronchoconstriction must be considered. It will be also discussed that the local application of Fenoterol on the upper part of the airways may influence also the reaction of the bronchial muscles in the lower part of the airways without a direct resorptive-systemic effect. The relationship of these findings for the clinical situation on man has to be investigated. PMID- 6248682 TI - [Plasma angiotensin-I-converting-enzyme activity after inhibition of prostaglandin synthesis (author's transl)]. AB - In 18 normal human volunteers plasma angiotensin-I-converting-enzyme (ACE) activity was measured before and after inhibition of prostaglandin synthesis by indomethacin. ACE activity did not change significantly after treatment. It is concluded that renin is probably the only component of the renin angiotensin system, which is influenced by prostaglandins. PMID- 6248683 TI - Increased activity of the Na-K-ATPase in red cell-ghosts of patients with Cushing's syndrome: possible significance for the pathogenesis of glucocorticoid induced hypertension. AB - The Na-K-ATPase activity of erythrocyte ghosts was increased in 6 patients with Cushing's syndrome compared with 28 control subjects (0.986 +/- 0.291 versus 0.259 +/- 0.1 microM Pi . h-1 . mg-1, p less than 0.001). Ouabain insensitive Mg ATPase activity was similar in both groups. These data support the concept of an activation of the Na-pump in patients with glucocorticoid excess. PMID- 6248685 TI - Amplification of cell membrane surface in potassium adaptation. PMID- 6248684 TI - [Problem of using dehydrated food products in long-term space flights]. AB - The paper discusses the results of five studies on 35 test subjects conducted to test diets of dehydrated products to be used in prolonged space flights. The studies have demonstrated that a diet consisting of only dehydrated food products can be used for a prolonged time (up to 1 year). Dehydrated foods after a 2-year storage and proton irradiation at a dose of 24,000 rad retain their biological value and assure an adequate nutritional status. On this basis a space diet composed of dehydrated foods has been developed. PMID- 6248686 TI - The respective roles of membrane cholesterol and of sodium potassium adenosine triphosphatase in the pathogenesis of lithocholate-induced cholestasis. PMID- 6248687 TI - Binding specificity of the rat serum vitamin D transport protein. PMID- 6248688 TI - Androgen receptor in cultured interstitial cells derived from immature rat testis. PMID- 6248689 TI - A radioimmunoassay for equilin in post-menopausal plasma: plasma levels of equilin determined after oral administration of conjugated equine oestrogens (premarin). PMID- 6248690 TI - Serological evaluation of human brain tumors using a microradioisotopic staphylococcal protein A assay. AB - A microradioisotopic staphylococcal protein A assay was applied to the serological evaluation of preoperative sera from brain tumor patients. The assay was performed in Terasaki plates, and a stainless steel punch and multiholed die facilitated sample prearation. Using allogeneic astrocytoma target cells, 15/19 of the brain tumor patients' sera were reactive, compared to 1/21 controls 0/7 nonmalignant brain disease patients' sera were positive, and 5/20 sera from patients with epithelial malignancies. The brain tumor sera were not reactive against a rectal cancer cell line. PMID- 6248691 TI - Pleomorphic adenoma of the human breast. AB - Pleomorphic adenomas of the human breast are histologically identical to those of salivary glands. To date, the literature reports but 15 such benign tumors, all of which occurred in women. The present paper describes clinical and pathologic findings in three further cases, including one man. Considered together, unnecessary mastectomy occurred in 44.4%, indicating the importance of separating this benign entity from malignancies with stromal metaplasia. In case of examination by frozen section, a peripheral portion, if not the entire tumor, should be submitted to the pathologist. PMID- 6248692 TI - A modified paper-binding procedure for the assay of nucleus-associated protein phosphokinases. AB - Previously existing paper-binding assay procedures gave results with large variations when employed for the measurement of nucleus-associated protein phosphokinase activities. However, a modified method, utilizing the binding of 32P-labeled phosphoprotein substrates to paper and employing washing procedures in 20% trichloroacetic acid at 60 degrees to 70 degrees C, gave highly reproducible results. This modified procedure was satisfactory with either chromatin or a nonhistone protein fraction derived therefrom as a source of enzyme, and dephosphophosvitin, lysine-rich histones, or casein as phosphoprotein substrates. PMID- 6248693 TI - Modification of mitochondrial respiration by aging and dietary restriction. AB - Effects of aging and of dietary restriction on mitochondrial recovery and respiratory capacities have been assessed in mice. Old mice (23-26 months) did not differ from adult mice (9-12 months) in amounts of protein recovered in mitochondrial fractions of liver, brain and spleen, but did show a decline in specific activity of cytochrome c oxidase (cyt. c ox.) in liver and spleen. Age effects on in vitro respiration by mitochondria occurred in liver and spleen. In liver, only one substrate (beta-hydroxybutyrate) of four tested was respired at a different rate by old than by young mitochondria. Depression of state 3 respiration and 2,4-dinitrophenol (DNP)-uncoupled rates was observed for this substrate; however, this effect depended on expressing respiration on the basis of mitochondrial protein and was less overt if data were expressed per unit of cyt. c ox. activity. Old spleen mitochondria exhibited a grosser defect, showing a 40% decrease in the respiratory control index (RCI) for (succinate + rotenone)- supported respiration (the only substrate tested) due to a possible increase in state 4 rates. Effects of dietary restriction were assessed in liver and brain of 3-7-month-old mice underfed since weaning. Dietary restriction reduced recovery of total liver mitochondrial protein and liver cyt. c ox. specific activity. Liver mitochondria from restricted mice generally showed increased state 3 rates with no differences from controls in state 4 rates for respiration supported by glutamate or pyruvate + malate, resulting in an increased RCI for these substrates. DNP-uncoupled rates were also raised by dietary restriction. Unlike effects observed in old versus young mice, these differences obtained whether the data were expressed on the basis of mitochondrial protein or on cyt. c ox. activity. Electron microscopy of liver mitochondrial preparations revealed more non-mitochondrial contaminants in old mice and larger mitochondria in dietarily restricted mice. These findings are compatible with reports of age-dependent losses of liver mitochondria and suggest that dietary restriction may retard this loss. PMID- 6248694 TI - The electron spin resonance spectrum of a suicidal fungus. AB - The electron spin resonance spectrum of a suicidal inositol auxotroph of Neurospora crassa, previously used as a model of cellular aging, exhibits a high spin Fe(III) signal whose intensity increases as a function of the mutant's "senescence". Surprisingly, the intensity of the signal is further enhanced by the exogenous antioxidant nordihydroguaiaretic acid, which reportedly decreases the rate of senescence. PMID- 6248695 TI - [Methodology and results of a phase IV study in gastrology]. PMID- 6248696 TI - Viral pneumonias. PMID- 6248697 TI - [Progress in the treatment of bronchial small-cell carcinoma]. PMID- 6248698 TI - 3H-Dihydromorphine binding in brain regions of young and aged rats. PMID- 6248699 TI - On the role of extracellular Ca2+ for prolactin release and adenosine 3':5' monophosphate formation induced by thyroliberin in cultured rat pituitary cells. PMID- 6248700 TI - Long-term blockade of angiotensin converting enzyme alters passive ion transport of vascular smooth muscle. PMID- 6248701 TI - Radioautography of binding of tritiated diprenorphine to opiate receptors in the rat. PMID- 6248702 TI - beta-adrenergic supersensitivity in rat brainstem during clonidine withdrawal. PMID- 6248703 TI - The effect of theophylline on adenosine 3',5'-monophosphate-dependent protein kinase and ACTH1-24 stimulated steroidogenesis in bovine adrenal cortical cells. PMID- 6248704 TI - Role of phosphatidylinositol turnover in alpha 1 and of adenylate cyclase inhibition in alpha 2 effects of catecholamines. PMID- 6248705 TI - Effect of thyrotropin releasing hormone on the cAMP content in circumesophageal ganglia of Lymnaea emarginata. PMID- 6248706 TI - Ouabain-insensitive sodium/lithium exchange and the effect of anti-L in low potassium sheep erythrocytes. PMID- 6248707 TI - Activation of human breast carcinoma collagenase through plasminogen activator. PMID- 6248708 TI - A comparison of ethanol, acetaldehyde and trichloroethanol effects on ganglionic transmission. PMID- 6248709 TI - A protein-lipid model of the opiate receptor. PMID- 6248711 TI - Change of nuclear ribonuclease H activity following deoxyribonucleic acid synthesis in liver of protein-deficient rat. PMID- 6248710 TI - Anaphylaxis and plasma catecholamines. PMID- 6248712 TI - Concentration-dependent inhibition of myosin ATPase by an indole metabolite of epinephrine. PMID- 6248713 TI - Evidence that opiate receptors mediate suppression of hypertonic saline-induced drinking in the mouse by narcotic antagonists. PMID- 6248714 TI - A radioimmunoassay for gamma-melanocyte stimulating hormone. PMID- 6248715 TI - The pharmacologic control of adrenal steroidogenesis. PMID- 6248716 TI - Comparisons of monoacylglycerols and diacylglycerols of varying fatty acid composition as substrates for the acylglycerol kinase(s) of rat brain. PMID- 6248717 TI - [Pyrophosphate-99mTc scintigraphy in detecting bone lesions and controlling therapy effectiveness in lymphogranulomatosis]. PMID- 6248718 TI - Cytomegalovirus disease in renal allograft recipients: a prospective study of the clinical features, risk factors and impact on renal transplantation. AB - Fifty-nine renal transplant recipients with overt CMV disease were treated at the University of Minnesota Health Sciences Center between October 1, 1977 and November 15, 1978. In a group of 141 consecutive transplant patients, the incidence of overt CMV disease was 31%. Fifty-three patients (90%) developed clinical manifestations of CMV disease within 4 months of transplantation, and it was during this time period that overt CMV disease was associated with a significantly increased incidence of transplant nephrectomy and death. Fever was the most common presenting symptom (95% of patients), and overt CMV disease was found to be the single most common cause of fever in all hospitalized transplant recipients. Prolonged fever, diffuse pulmonary infiltrates, gastrointestinal bleeding, pancreatitis, transplant nephrectomy and development of other systemic infections were clinical features used to categorize patients according to disease severity. A number of these features were found to be significantly associated with the diagnosis of overt CMV disease. Twelve patients (20%) developed lethal CMV disease characterized by the presence of most of these features, 6 (10%) had severe disease, 9 (15%) had disease of moderate severity and 32 patients (54%) had mild CMV disease with fever being essentially their only clinical finding. Development of secondary systemic infection was most ominous, and occurred before death in 10 of the 12 patients with lethal CMV disease. The only patients to die with serious bacterial, fungal or protozoan infection during the period of this study had concomitant overt CMV disease. Abnormal liver function tests and leukopenia were common, and the degree of abnormality correlated with the severity of CMV disease. Of the multiple factors analyzed for their influence on the risk of developing overt CMV disease, several factors related to the kidney donor (the relationship of the donor to the recipient, HLA matching and CMV serology) appeared to be most important. PMID- 6248719 TI - Plasma cell neoplasia with peripheral polyneuropathy. A study of five cases and a review of the literature. AB - Peripheral polyneuropathy (PPN) is a rare complication of plasma cell neoplasia (PCN), occurring in less than one percent of the patients. Fifty-four such patients (including our 5) were reviewed. There were 42 men (78%) and 12 women (22%) aged 28 to 72 years. Forty-nine percent of patients were younger than 51 years at the time of diagnosis. The initial complaints were different from those observed in multiple myeloma in general, and were related to polyneuropathy in 80% of the patients. PPN was usually of a mixed sensory-motor type and most often involved all four extremities. Skeletal pain was less common than in myeloma in general, occurring initially in 15% and at diagnosis in 45% of the patients. In 21 patients, reversibility of neuropathy was observed. These patients were compared to those with irreversible neuropathy and found to be relatively younger and more aggressively treated with irradiation and modern chemotherapy. Elevated sedimentation rate was uncommon. Less than half of the patients had anemia, and six patients, all with osteosclerotic lesions, had polycythemia. Azotemia was detected in 44% of the cases. No hypercalcemia was observed in 21 examined patients. M components were usually of IgG class, and when the light chains of M components were examined they were invariably of lambda type. Often the level of M component was below 2.0 g/dl. In all patients the bone marrow was infiltrated with immature, abnormal-looking plasma cells, but the infiltrate was often limited to one or a few foci. Solitary plasmacytoma was observed in 14 patients. No anemia, hypercalcemia or azotemia was recorded in this group. Eight patients had serum M components. Bone marrow aspirate was usually normal. In seven patients definite reversibility of PPN was observed after irradiation of plasmacytoma. Twelve patients presented with osteosclerotic lesions (22%), 18 with both osteosclerotic and osteolytic lesions (33%) and 13 with osteolytic lesions. Forty-two percent of the patients had less than three visible lesions in the skeleton. Eleven patients had either osteoporosis or radiologically normal skeleton. The mean survival from the first symptom was about 28 months and from the diagnosis 20 months. The five-year survival was 21% and 20%, respectively. These observations highlight the differences between PCN with PPN and multiple myeloma without PPN. PMID- 6248720 TI - Plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes: the POEMS syndrome. Report on two cases and a review of the literature. AB - Two patients with plasma cell dyscrasias, manifested by osteosclerotic bone lesions and small amounts of M protein, and a complicating multi-system disorder are described. Their features of severe sensory-motor polyneuropathy, organomegaly, endocrine dysfunction, anasarca, elevated CSF protein, and skin hyperpigmentation are similar to a clinical syndrome reported primarily in Japanese men. Two previously unrecognized findings--hyperprolactinemia and an unusual radiographic abnormality of fluffy, spiculated bony proliferation--may facilitate recognition of the syndrome. The relationship of these various manifestations to the plasma cell dyscrasia is unknown, but a number of possibilities are discussed. PMID- 6248721 TI - Polarographic measurement of steady state kinetics of oxygen uptake by biochemical samples. PMID- 6248722 TI - Genetics and physiology of the rel system of Bacillus subtilis. AB - Stringent factor (ATP:GTP-3' pyrophosphotransferase) has been purified from wild type Bacillus subtilis and it has been shown that guanosine tetra- and pentaphosphate (ppGpp and pppGpp) are synthesized in vitro in the presence of ribosomes, unacylated tRNA and its specific codon, as has been demonstrated in Escherichia coli. relA, the genetic determinant for the stringent factor, has been mapped on the B. subtilis chromosome by transduction and is found between aroD and leu. The relC locus, defined by mutations which were originally selected by resistance to thiostrepton, has been mapped adjacent to spoOH in the order cysA, spoOH, relC, rif. Sringent factor and ribosomes are functional for the in vitro synthesis of (p)ppGpp in early stages of sporulation (up to at least 4 h). This contradicts the findings of other laboratories. PMID- 6248723 TI - IS4 is still found at its chromosomal site after transposition to galT. AB - IS4-DNA has been hybridized to separated DNA fragments of E. coli K12 strain M28 and to three mutants caused by transposition of IS4 to galT. The parental strain shows one band hybridizing to IS4 representing one copy of IS4 in the chromosome. The mutants have this copy retained and show in addition a second band corresponding to the IS4 copy in galT. The experiments support the hypothesis that transposition of IS4 is accompanied by replication of the element. PMID- 6248724 TI - IS4 at its chromosomal site in E. coli K12. AB - IS4 DNA has been isolated in pure form. Hybridization of this DNA against restricted DNA of several E. coli K12 strains by Southern's blotting technique has shown that, in most strains, only one copy of IS4 is present. Though the restriction fragments around this site differ in size, IS4 can be shown always to be located at the same site. In one strain, one additional copy has been found in a new location. In this strain, IS4 in its original location has been retained. PMID- 6248725 TI - Isolation of viable deletion mutants of Streptomyces actinophage (Pal 6) and their molecular characterization. AB - Deletion mutants of bacteriophage Pal 6 were isolated by successive treatments of either heat (60 degrees C) or pyrophosphate (10 mM). These mutants were characterized by restriction enzyme cleavage analysis. The pyrophosphate resistant clones lost the whole Eco R1 fragment in which the Sal I site is located, as well as an unrelated Hind III fragment. These results show that the region containing the Sal I site in the phage genome is not essential for phage viability. This single Sal I site is therefore suitable as a potential insertion site for DNA cloning. On the other hand, the heat resistant clones that were isolated and characterized do not appear to have detectable deletions as indicated by their Eco R1 DNA digestion pattern. PMID- 6248726 TI - Isolation of a polynucleotide phosphorylase mutant using a kanamycin resistant determinant. AB - Insertion in an episome of a kanamycine-resistant element (Tn5) at the polynucleotide phosphorylase gene level, results, after transduction into a wild strain, by the loss of activities specific to polynucleotide phosphorylase. A low phosphorolytic activity is nevertheless detectable in crude extracts, but no longer in extracts slightly purified after heat treatment at 54 degrees C. The part played by other enzymes in these activities is discussed. Bacterial growth is not affected by introduction of the mutation. PMID- 6248727 TI - Deletions and an inversion induced by a resident IS1 of the lactose transposon Tn951. AB - DNA-DNA filter binding tests, "Southern" blotting experiments and DNA heteroduplex analysis clearly show that Tn951 contains an IS1 element. This IS1 951 sequence is peculiar in that it does not contain the PstI cleavage site which is usually observed on E. coli derived IS1 elements. Nonetheless, IS1-951 induces deletions. This process is temperature dependent. One instance of an IS1-951 induced inversion was observed, the structure of which is compatible with the current models of transposition of IS elements. PMID- 6248728 TI - The use of plasmid R1162 and derivatives for gene cloning in the methanol utilizing Pseudomonas AM1. AB - A physical map for plasmid R1162 (Sm, Su, IncP4) was constructed. Neither EcoRI, PstI nor EcaI cut within a region essential for replication, molbilization or streptomycin resistence. Plasmid R1162 can replicate in E. coli as well as in Pseudomonas species and shows a strong dependence for DNA polymerase I in E. coli. By RP4 induced mobilization, R1162 can be transferred from E. coli to Pseudomonas AM1. A hybrid plasmid pFG7 (MW=8.4 x 10(6), Sm, Su, Ap, Tc) was constructed between pBR322 and R1162, which allows the selection of hybrid plasmids by insertional inactivation with the restriction enzymes HindIII, BamHI, SalI, ClaI. Transformation of E. coli SK1592 with Ecal-cut and ligated R1162-DNA and Pseudomonas AMI-DNA and subsequent mobilization of the hybrid plasmids into Pseudomonas AM1/M15a (methanol dehydrogenase-) led to the isolation of Pseudomonas AM1/M15a colonies, which could grow on methanol again. Back conjugation into E. coli SK1592, subsequent mobilization studies and plasmid analysis suggests that the gene for Pseudomonas methanol dehydrogenase has been cloned in this vector. PMID- 6248729 TI - On the role of the dnaB protein of Escherichia coli in the replication of lambda bacteriophage DNA. AB - The interaction between the dnaB protein of E. coli and the gene P product of lambda bacteriophage was investigated by measuring the cleavage of closed circular phage DNA after infection of two temperature sensitive dnaB mutants, JG28 and To534 groP- B. Cleavage of superhelical DNA from a lambda pi B mutant phage was observed after infection of either strain whereas superhelical DNA from a wild type phage was only cleaved after infection of JG28. When DNA synthesis in infected cells was blocked by incubation at the nonpermissive temperature, no inhibition of superhelical phage DNA cleavage was observed. It is concluded that in conditions where the dnaB protein has lost the capacity to function in nucleotide polymerization, it is capable of interacting with the lambda replication gene products to introduce a break in the phage DNA. PMID- 6248730 TI - Does the insertion element IS1 transpose preferentially into A+T-rich DNA segments? AB - IS1-mediated insertion and deletion formation occur preferentially into A+T-rich regions of DNA of bacteriophate P1 and of the r-determinant of the R plasmid NR1. The significance of this correlation is discussed in view of other published data. PMID- 6248731 TI - Construction and properties of a new cloning vehicle, allowing direct screening for recombinant plasmids. AB - pUR2, a certified B2(EK2) vector, allows easy isolation of variants containing cloned EcoRI-fragments. Bacteria harboring plasmids without inserts make blue colonies on indicator-plates, whilst those harboring recombinant plasmids make white colonies. PMID- 6248732 TI - Anatomy of mitochondrial DNA from Paramecium aurelia. AB - The linear genome of mitochondrial DNA from four species of Paramecium aurelia was investigated with respect to restriction endonuclease fragments, location and number of ribosomal RNA genes, and interspecies EcoRI and HindIII fragment homologies. One copy of each of the rRNA genes was found in all four species and the 14s and 20s rRNA genes were separated by at least 3,000 bp. R-Loop analysis of the 20s rRNA gene did not reveal the presence of an intervening sequence. Interspecies homology studies showed species 1, 5, and 7 to have a high degree of homology but species 4 was less than 50% homologous to species 1 mt DNA. For all four species, rRNA genes showed good homology indicating that these DNA sequences are highly conserved, even between species having many non-homologous regions. A major region of DNA which displayed little homology between species 1 and 4 was that fragment containing sequences essential for initiation of DNA replication. PMID- 6248733 TI - A temperature-sensitive Escherichia coli mutant defective in DNA replication: dnaN, a new gene adjacent to the dnaA gene. PMID- 6248734 TI - Genetic recombination of herpes simplex virus, the role of the host cell and UV irradiation of the virus. AB - Recombination frequencies for two sets of genetic markers of herpes simplex virus were determined in various host cells with and without ultraviolet irradiation of the virus. UV irradiation increased the recombination frequency in all the cell types studied in direct proportion to the unrepaired lethal damage. In human skin fibroblasts derived from a patient with xeroderma pigmentosum (XP) of complementation group A, a given dose of UV stimulated recombination more than that in fibroblasts from normal individuals. On the other hand, UV stimulation of HSV recombination was slightly less than normal in fibroblasts derived from a patient with a variant form XP and from an ataxia telangiectasia patient. Caffeine, an agent known to inhibit repair of UV damage, reduced recombination in most of the cell types studied and did not suppress the UV-induced increase in recombination. These findings suggest that for virus DNA with the same number of unrepaired UV-lesions, each of the tested cell types promoted HSV-recombination to an equivalent extent. PMID- 6248735 TI - Complementation of T4 phage am mutations by hybrid phages lambda-T4. AB - EcoRI fragments of the T4 cytosine-containing DNA (dC-DNA) were cloned in the lambda XIII vector phage carrying the only restriction site for EcoRI in the repressor gene of lambda. 38 genes of T4 were identified in the cloned fragments by means of marker rescue technique. All cloned early genes and some late genes of T4 were able to complement a corresponding am mutations of T4 phage when nonpermissive cells of E.coli were simultaneously infected with hybrid phages lambda-T4 and am mutants of T4. An average burst size for am mutants from su- cells (when complemented by corresponding hybrid phage) was 20-70 pfu for early genes and 1-3 to 20 pfu for late ones. When the extract of cells infected with hybrid phage lambda-T4-22 containing T4 genes 57, 1, 2, 64 was mixed with the extract of cells infected with T4N51 mutant, the complementation in vitro was observed. So, it was shown that normal product of late gene 2 is synthesized in the cells infected with hybrid phage lambda-T4-22 in the absence of positive regulators of transcription coded by early T4 genes. PMID- 6248737 TI - Molecular cloning of EcoRII endonuclease and methylase genes. AB - The genes for restriction-modification system EcoRII have been cloned from plasmid N3 DNA using RSF2124 as a vector plasmid. The hybrid plasmids designated pFK321 and pFK322 contained a 5.8 megadaltons EcoRI--fragment derived from N3 DNA including the genes for restriction-modification system EcoRII and a gene for resistance to sulfanilamide. PMID- 6248738 TI - Electron microscopic observation of new transposable elements inserted into P22 phage genome from R plasmids. AB - By using phage P22spl, a deletion mutant of phage P22, the structures of two new transposons on P22 genomes were studied by the electron microscopic heteroduplex method. One of these was the Cm (chloramphenicol) transposon derived from an R plasmid, NR1, and the other the Km (kanamycin) transposon frin obr502. the heteroduplex between P22 phage DNAs with and without the Cm transposon revealed that the Cm transposon was similar in structure to the Tn9 element, a well-known Cm transposon derived from the R plasmid pMS14. On the other hand, the Km transposon of pNR502 was quite different in structure from other Km transposons reported previously. This transposon consists of a 6.8 kilobase (kb) segment of DNA, in which a short inverted repeat is contained. The heteroduplex experiments showed that a 4.5 kb segment of DNA was deleted from the P22 genome in the P22spl genome. Because of a shorter unit length of the genome, phage P22spl is considered to be useful of assaying various kinds of transposable elements. PMID- 6248736 TI - Transposition of the kanamycin-resistance transposon Tn903. PMID- 6248739 TI - [Effectiveness of bacterization of soy plants by active races of nodule bacteria]. AB - Spontaneous nodule bacteria of soybean plants are absent from the Sutn-Eastern Kazakhstan soils. Therefore, bacterization of soybean plants with these bacteria is necessary for obtaining high crops of this culture. Among tested strains of soybean nodule bacteria, strain 623(a) was found to be the most effective one. The use of nitrogen with this strain stimulated the intensive formation of nodules, the growth and development of plants, the activation of physiological processes in them, and increased the yield of green mass, hay and grains as well as the content of protein in them and its yield per area unit. Mineral nitrogen added to soil at a concentration of 120 kg per hectare decreased the activity of symbiotic nitrogen fixation, increased the crop of green mass and hay, but decreased the yield of grain of soybean and other cultures sown after it in crop rotation. PMID- 6248740 TI - [Isolation and certain features of a polyphosphate phosphohydrolase deficient mutant of the fungus Neurospora crassa]. AB - A polyphosphatase deficient mutant of Neurospora crassa has been isolated. The criterion for selecting the mutant was the capacity of the fungus to assimilate polyphosphates as the source of exogenous phosphorus. The mutant like the parent strain ad-6, was an adenine auxotroph but differed from the parent strain by a lower growth rate though, at the stationary stage, its biomass reached the same level as in the strain ad-6. The character of changes in the activity of polyphosphatase in the course of growth was the same in the two cultures, but the activity of the enzyme in the mutant was considerably lower at all the growth stages. The content of polyphosphate fractions with the highest molecular weight increased twofold in the mutant culture. These data suggest that there is a close metabolic and topographic correlation between polyphosphatase and the highest molecular weight fractions of polyphosphates in N. crassa. PMID- 6248741 TI - [Respiratory resistance of methylotrophic bacteria to formate and cyanide]. AB - Whole cells and cell-free preparations of the methylotrophic bacteria, Pseudomonas sp. AM 1 and Achromobacter parvulus, can oxidize formate at tis concentration in the reaction medium up to 1 M. The respiration of whole cells is registered at a concentration of formate greater than 10(-2) M, while that of cell-free extracts at a formate concentration greater than 5 X 10(-5) M. This seems to be due to the presence of a permeability barrier in cells for formate. The oxidation of reduced TMPD and exogenous cytochrome c by the membrane preparations of the two bacteria is inhibited by formate and cyanide; Ki50% = 2.5 X 10(-2) and 10(-6) M, respectively. The oxidation of NADH by the membrane preparations of the bacteria is not inhibited by 1 M formate and 5 X 10(-4) M cyanide but is inhibited by formaldehyde with Ki50% = 3 X 10(-2) M. Formaldehyde has no effect on the oxidation of reduced TMPD and cytochrome c at concentrations greater than 2 X 10(-1) M. These data indicate that respiration of the studied methylotrophic bacteria in the presence of high formate concentrations should be attributed in the presence of a branched electron transport chain in them; one branch of the chain is resistant to formate and cyanide, but is sensitive to formaldehyde. PMID- 6248742 TI - [Microorganisms that produce alpha-galactosidase, alpha-mannosidase, alpha fucosidase and beta-acetylglucosaminidase]. AB - The capacity to synthesize alpha-D-galactosidase (EC 3.2.1.22), alpha-D mannosidase (EC 3.2.1.24), alpha-L-fucosidase (EC 3.2.1.51) and beta-D acetylglucose aminidase (EC 3.2.1.30) was tested among 100 different cultures of soil microscopic fungi and actinomycetes. Two genera of micromycetes, viz. Scopulariopsis and Aposphaeria, which had not been known as producing alpha-D galactosidase, were found, as well as several new species of the genus Penicillium: Pen. canescens, Pen. claviforme, Pen. cyclopium, Pen. daleae, Pen. frequentans, Pen. piscarum, Pen. simplicissimu, Pen. thomii. PMID- 6248743 TI - [Effect of polymyxins on Bacillus polymyxa sporogenesis]. AB - Bacillus polymyxa var. Ross. producing polymyxin M and Bacillus polymyxa 153 producing polymyxin B form spores during submerged cultivation when the rate of biosynthesis of antibiotic peptides is low and when the production of antibiotics is over. However, sporogenesis is stimulated if polymyxins are added at the early stage of cultural growth. Inhibition of the synthesis of antibiotics suppresses the formation of spores. Substances other than polymyxins do not exhibit such a specific effect on sporogenesis. The fact that the culture requires endogenous polymyxins which are most effective in the period prior to the appearance of spores in the culture suggests the regulatory action of these peptides at the stage between vegetative growth and spore formation in Bacillus polymyxa. PMID- 6248745 TI - Strachan's syndrome 30 years after onset. AB - While a prisoner-of-war in Malaya from 1942-1945, a 29-year-old man developed a painful sensorimotor neuropathy, bilateral central scotomata and sensorineural deafness. Examination 34 years later, after a long period of adequate nutrition, revealed considerable residual deficit. Nerve conduction studies suggested axonal degeneration with prominent collateral reinnervation. This case of Strachan's syndrome is reported to draw attention to the limited functional recovery and to focus attention on this condition at a time when famine conditions are rife in Southeast Asia. PMID- 6248744 TI - Neuromuscular junction macromolecules in the pathogenesis of amyotrophic leteral sclerosis. AB - An hypothesis regarding the pathogenesis of amyotrophic lateral sclerosis is presented, which places emphasis on extraneural cells. Classical experimental denervation is compared and contrasted with motor neuron disease, both from information in the literature as well as concepts deriving from the hypothesis. Background information regarding neuromuscular junction-specific (16S) acetylcholinesterase and a basal lamina-enriched surface glycoprotein (fibronectin) are presented, which suggest not only their mutual interaction, but likely parallel regulation on muscle cell surfaces by the motor nerve. Since 16S acetylcholinesterase likely contains basal lamina-type collagen and fibronectin specifically associates with collagen, a model relating activation of latent collagenase enzyme in amyotrophic lateral sclerosis is described. It is suggested that continued degeneration, including transneuronal effects, of the motor system ensues from random, continuous loss of nerve-muscle adherence resulting from collagen resorption at the neuromuscular junction. PMID- 6248746 TI - Medium-dose methrotrexate/folinic acid regimen in the chemotherapy of gestational trophoblastic disease. AB - Under the aegis of the Queensland Trophoblastic Tumour Registry, a screening and monitoring programme with the beta-subunit of chorionic gonadotrophin as a marker was adopted in the management of patients with gestational trophoblastic disease. Twenty-six patients had been treated with pulses of methotrexate, followed by folinic acid rescue, up to a total dose of 200 mg of methotrexate in each course; the side effects were minor and infrequent. This regimen was effective in producing biochemical and clinical remission in 18 of 19 patients both with non metastatic and with metastatic persistent disease; the mean duration of treatment was nine weeks and 19.2 weeks respectively. However, it was effective in only three of seven patients with histologically confirmed choriocarcinoma, which suggests that a more aggressive multidrug regimen should be considered from the outset in this high risk group of patients. Our preliminary data have revealed no permanent effects on subsequent fertility or observable effects on the babies so far studied. PMID- 6248747 TI - Association of respiratory virus infections with sudden infant death syndrome. AB - From September, 1974, to September, 1979, 488 cases of sudden infant death syndrome (SIDS) in Melbourne were studied for evidence of viral infection. One hundred and eighty-eight infants (39%) yielded one or more viruses, with respiratory viruses being detected in 102 cases (21%). Further evidence of a respiratory virus association with SIDS was obtained by comparing the monthy respiratory virus isolation rates at the Royal Children's Hospital from 1973 to 1979 with the incidence of SIDS in the same period. A highly significant correlation was obtained between these isolation rates and the incidence of SIDS, which suggests that respiratory viruses play a role in SIDS in Melbourne. PMID- 6248748 TI - [Irritable colon: the most frequent functional disorder of the gastrointestinal tract]. PMID- 6248749 TI - [Formal medicine/paramedicine. Is a synthesis possible?]. PMID- 6248750 TI - [Insulin action: receptor binding and signal relay]. PMID- 6248751 TI - Nobel Award address. Early two-dimensional reconstruction and recent topics stemming from it. PMID- 6248752 TI - Spot scanning system for proton radiotherapy. AB - In order to provide a uniform and desirable dose distribution over a large radiation field, spot beam scanning is one of the most useful methods. A new spot beam scanning system was constructed for a 70 MeV proton beam. The lateral dose distribution was uniform with +/- 2.5% for an 18 cm square field. It was possible to control the dose at each point in the radiation field by this spot scanning method. This system has been confirmed to be satisfactory for delivering a proton beam in the desired field shape and dose level. PMID- 6248753 TI - [The Aarskog syndrome. Description of a case and review of the literature]. PMID- 6248755 TI - Decreased responsiveness of the adenylate cyclase system on left atria from hypothyroid rats. PMID- 6248754 TI - Nereistoxin interaction with the acetylcholine receptor-ionic channel complex. PMID- 6248756 TI - Lipid-protein interactions in the multiple forms of monoamine oxidase. Enzymatic and ESR studies with purified intact rat brain mitochondria. PMID- 6248757 TI - Activation of rat cerebral cortical 3',5'-cyclic nucleotide phosphodiesterase activity by gangliosides. PMID- 6248758 TI - Effects of antiandrogens (cyproterone acetate and flutamide) on the activity of nuclear protein phosphokinases and phosphatases of rat ventral prostate. PMID- 6248760 TI - The reductive metabolism of metronidazole and ronidazole by aerobic liver microsomes. PMID- 6248759 TI - Spin trapping of the primary radical involved in the activation of the carcinogen N-hydroxy-2-acetylaminofluorene by cumene hydroperoxide-hematin. PMID- 6248761 TI - Epidermal growth factor-urogastrone: biological activity and receptor binding of derivatives. PMID- 6248762 TI - Effects of delta 9-tetrahydrocannabinol on excitable membranes and neuromuscular transmission. PMID- 6248763 TI - Stimulation of superoxide formation by actinomycin D and its N2-substituted spin labeled derivatives. PMID- 6248764 TI - Self-inactivation of an erythrocyte NAD glycohydrolase. AB - NAD glycohydrolase activity was studied using bovine erythrocytes, erythrocyte ghosts and partially purified enzyme preparations. During catalysis the enzyme becomes irreversibly inactivated in a process related to substrate turnover. Self inactivation was observed with intact cells, ghosts and solubilized enzyme and could be demonstrated with NAD, NADP and nicotinamide 1,N6 ethenoadenine dinucleotide as substrates. Thionicotinamide adenine dinucleotide and NADH, which are not substrates for the enzyme, do not inactivate but are reversible substrate competitive inhibitors. Added thiols had no effect on enzyme self-inactivation. Of the reaction products, added nicotinamide partially protected the enzyme while added ADPR had no effect. Thermodynamic parameters calculated from Arrhenius plots for rate constants of self-inactivation indicate a large negative delta S for transition state formation suggesting a process other than extensive denaturation. Erythrocyte ghost NADases from several other mammalian sources have been demonstrated to undergo a self-inactivation similar to that observed with the bovine enzyme. PMID- 6248765 TI - The divalent cation dependence of liver glycogen synthase phosphatase activity. PMID- 6248766 TI - Characterization of plant satellite DNA using restriction nucleases. AB - The structural organization of satellite DNAs of mustard Brassica nigra and lemon Citrus limon has been studied by digestion with restriction nucleases. Analysis of DNA products produced by EcoRI and Bam I shows that two satellite DNAs contain long range periodicities belonging to several repeated sequences. The periodicities in two satellite DNAs differ characteristically, however, they have been found to contain common homologous sequences. Using the restriction nuclease Bsp I, a highly periodical fractions has been found in Citrus satellite DNA, composed of Bsp I fragments ranging from 80 to 1240 basepain. The major repeat units comprise five Bsp I fragments ranging from 80 to 200 bp. These fractions characterized by a high content of 5-methyl-cytosine. PMID- 6248767 TI - Conformational transitions in closed circular DNA molecules. I. Topological and energetical considerations. AB - A theory of conformational transitions in closed circular DNA as a function of topological linking number of the molecule (alpha) is elaborated taking into account topological and energetical considerations. The theory predicts a step like dependence of a number of superhelical turns in DNA molecules (tau) on delta alpha. Thus, the number of superhelical turns tau = delta alpha for small values of delta alpha. For a large delta alpha (when conformational begin to occur) tau = delta alpha - sigma phi ij, where sigma phi ij is the total angle of conformational transitions for a given delta alpha. This prediction is in good agreement with published data on the dependence of the sedimentation coefficient of circular DNA molecules on their topological linking number. The results also allow to explain the disagreement between a number of titratable superhelical turns in circular DNA molecules and a number of supercoiles seen on electron micrographs for molecules with sufficiently large delta alpha. PMID- 6248768 TI - Binding of CRP to DNA-dependent RNA polymerase from E. coli: modulation by cAMP of the interactions with free and DNA-bound holo and core enzyme. AB - The regulatory protein CRP (or CAP) from E. coli is shown to display two distinct patterns of binding interactions with DNA-dependent RNA polymerase. The free core enzyme, and both the core and the holo polymerase when bound to single-stranded DNA, can bind CRP in a cAMP-independent association reaction. Instead, the binding of CRP to free holoenzyme and to holo or core polymerase bound to native DNA was undetectable in the absence of cAMP. The specific ligand of CRP (cAMP) strengthens distinctively this class of interactions. In no case could any release of sigma-factor be demonstrated. Estimates of the dissociation constants were obtained for the various binding reactions which were investigated under quasi-physiological ionic conditions. These, together with the known values of the in vivo concentrations of CRP and RNA polymerase, suggest that the interactions described may have a functional significance. PMID- 6248769 TI - Human C5a and C5a analogs as probes of the neutrophil C5a receptor. PMID- 6248770 TI - The management of cerebral disorders in the geriatric population: a pragmatic approach. PMID- 6248771 TI - Fibrous histiocytoma of the parotid gland. PMID- 6248772 TI - Phakomatoses in reproductive medicine. PMID- 6248773 TI - [Glycosaminoglycan inclusion bodies in leukocytes in patients with inflammatory rheumatic diseases]. PMID- 6248774 TI - [Availability of cefotaxime. Pharmacokinetic studies on the distribution in central and various peripheral compartments (author's transl)]. AB - After 2 g as a bolus injection the concentration of Cefotaxime was determined in serum, bone, tissue fluid, peritoneal exudate and bile under clinical conditions in 43 patients with a mean age of 61 years. Pharmacokinetic constants were calculated using a modified two compartment model. The basis for these calculations was a mean serum curve from 299 serum samples. The geometric mean and deviation factors of time-dependent values in tissue and tissue fluid are presented. The results are compared to the minimal inhibitory concentrations of pathogenic bacteria. The clinical success in 121 severe infections at a dose of 2 g every 12 hours support the theoretical results of this study. PMID- 6248775 TI - [Cephotaxim treatment in gynecology and obstetrics. Clinical experiences]. PMID- 6248776 TI - Comparison between inactivated Sendai virus, polyethylene glycol and Tween 80 as permeabilizing agents for introduction of neurospora endonuclease into X irradiated cells. AB - Inactivated Sendai virus, polyethylene glycol and Tween 80 were employed as agents to make X-irradiated CHO cells permeable for Neurospora endonuclease, in studies designed to evaluate the influence of this enzyme on the frequencies of X ray-induced chromosome aberrations. Polyethylene glycol and Tween 80 were found not to be very efficient in making cells permeable. Besides, polyethylene glycol was found to increase the frequencies of X-ray-induced chromosomal aberrations. PMID- 6248777 TI - UV-reactivation, virus production and mutagenesis of SV40 in VU-irradiated monkey kidney cells. AB - The survival of UV-irradiated simian virus 40 (SV40) is higher in VU-irradiated than in non-irradiated monolayers of BSC-1 monkey cells. A similar reactivation is found when cells are infected with SV40-DNA, suggesting that reactivation acts on viral DNA. The enhanced reactivation of VU-irradiated SV40 and SV40-DNA is optimal when infection is delayed for 2--3 days after irradiation of the cells. UV-pretreated cells infected with SV40-DNA produce more virus than infected control cells; the time curve of this process is similar to that found for enhanced virus reactivation and suggests that facilitated virus production in UV irradiated cells and enhanced virus reactivation might be manifestations of the same process. If the non-irradiated SV40 thermosensitive mutant BC245 is propagated in UV-irradiated BSC-1 cells the rate of back mutation to phenotypically wild-type is increased compared with that of the control. This suggests that an inducible error-prone system is functional in these cells. When the UV-irradiated tsBC245 is propagated in non-irradiated cells the reversion frequency is greatly enhanced, which suggest that either the introduction of UV irradiated SV40-DNA is sufficient to induce an error-generating system, or that a constitutive error-prone mechanism is operative on this DNA. PMID- 6248778 TI - Sensitization of rad mutants of Dictyostelium discoideum to ultraviolet light by postirradiation treatment with caffeine. PMID- 6248779 TI - The photoproduction of 1 alpha,25-dihydroxyvitamin D3 in skin: an approach to the therapy of vitamin-D-resistant syndromes. AB - Cutaneous 7-dehydrocholesterol, exposed to ultraviolet radiation, converts to previtamin D3, which in turn converts in skin to vitamin D3 and is carried into the circulation. We investigated the feasibility of the photochemical conversion in skin of hydroxylated derivatives of 7-dehydrocholesterol - such as 1 alpha, 25 dihydroxy-7-dehydrocholesterol (1 alpha, 25-(OH)2-7-DHC) - to the corresponding hydroxylated previtamin as an alternative method of delivery of 1 alpha, 25 dihydroxyvitamin D3 (1 alpha, 25-(OH)2-D3) to subjects who are deficient in the endogenous metabolite. In human volunteers and in vitamin-D-deficient rats [24 3H] 1 alpha, 25-(OH)2-D3 appeared in blood after [24-3H] 1 alpha, 25-(OH)2-7-DHC was applied to the skin and exposed to ultraviolet radiation. In anephric rats, intestinal calcium absorption and serum calcium levels were elevated after a topical dose of 1 alpha, 25-(OH)2-7-DHC combined with ultraviolet phototherapy. Delivery of equivalent doses of 1 alpha, 25-(OH)2-D3 through the skin and orally showed that there was more prolonged stimulation in intestinal calcium absorption and serum calcium elevation after cutaneous administration. The photochemical conversion of precursors may be useful in the treatment of patients with impaired vitamin-D metabolism. PMID- 6248780 TI - Transfer factor for the prevention of varicella-zoster infection in childhood leukemia. AB - Sixty-one patients with leukemia and no immunity to chickenpox were given dialyzable transfer factor or placebo and followed for 12 to 30 months in a double-blind trial designed to examine the clinical efficacy of transfer factor. Sixteen patients in the transfer-factor group and 15 in the placebo group were exposed to varicella zoster, and most of them had a rise in antibody titer. Chickenpox developed in 13 of 15 exposed patients in the placebo group but in only one of 16 in the transfer-factor group (P = 1.3 x 10(-5)). In the patients treated with transfer factor and exposed to varicella without acquiring chickenpox the titer of antibody to varicella zoster was equal to that in the patients given placebo who became infected with chickenpox. Transfer factor converted negative results on skin tests for varicella zoster to positive in approximately half the recipients. Passive immunization with dialyzable transfer factor appears useful in nonimmune persons. PMID- 6248781 TI - Therapeutic potential of transfer factor. PMID- 6248782 TI - The measurement of angiotensin-converting enzyme in subjects receiving captopril. PMID- 6248783 TI - Inhibition by retinoic acid of collagenase production in rheumatoid synovial cells. PMID- 6248784 TI - Physiology and pathophysiology of the human sympathoadrenal neuroendocrine system. PMID- 6248785 TI - Recent and past use of conjugated estrogens in relation to adenocarcinoma of the endometrium. AB - It has been suggested that the reported association between estrogen use and endometrial cancer may have been biased because estrogens provoke uterine bleeding in women with otherwise asymptomatic disease. To evaluate this hypothesis we compared 149 patients with endometrial cancer and 402 control subjects with other conditions with reference to the time when they had last used conjugated estrogens. In women who had last used conjugated estrogens two or more years previously and who had taken them for at least five years, the rate-ratio estimate was 3.3 (95 per cent confidence interval, 1.4 to 8.0) relative to women who had never used them. Uterine bleeding, and hence the diagnosis of otherwise asymptomatic cancer, cannot be attributed to estrogen use that ceased in the distant past. Our results suggest that such use has a residual effect on the risk of endometrial cancer; this effect is not accounted for by biased selection of cases according to estrogen use. PMID- 6248786 TI - Angiotensin-converting enzyme in substantia nigra of schizophrenics. PMID- 6248787 TI - Early steps in excision repair. PMID- 6248788 TI - Occam's razor. PMID- 6248789 TI - Cleavage of pyrimidine dimers in specific DNA sequences by a pyrimidine dimer DNA glycosylase of M. luteus. AB - Pyrimidine dimer formation in response to UV radiation is governed by the thymine content of the potential dimer and the two flanking nucleotides. An enzymatic activity can be purified from Micrococcus luteus that cleaves the N-glycosyl bond between the 5' pyrimidine of a dimer and the corresponding sugar without rupture of a phosphodiester bond. We propose that strand scission at a dimer site by the M. luteus enzyme requires two activities, a pyrimidine dimer DNA-glycosylase and an apyrimidinic/apurinic endonuclease. PMID- 6248790 TI - Lack of M-MuSV tumour regression associated with T lymphocyte tolerance. PMID- 6248791 TI - Presence of a low molecular weight endogenous inhibitor on 3H-muscimol binding in synaptic membranes. AB - The specific binding of 3H-muscimol to synaptic membrane preparations obtained from the rate brain has been though to reflect the association of gamma aminobutyric acid (GABA), a potential candidate as an inhibitory neurotransmitter in the mammalian central nervous system (CNS), with its synaptic receptors. Treatment of synaptic membranes with Triton X-100 significantly increases the specific binding of 3H-muscimol. Several reports also indicate the presence of endogenous substances, such as GABA, acidic protein and phosphatidylethanolamine, which inhibit Na-independent binding of 3H-GABA in the synaptic membranous fractions from the rat brain. We report here that in the supernatant obtained from Triton-treated synaptic membranes there exists a new type of endogenous inhibitor of 3H-muscimol binding which is apparently different from the inhibitory substances described previously. The new inhibitor has a low molecular weight (MW) and probably originated from neurones rather than glial cells. We have termed this endogenous inhibitor the GABA receptor binding inhibitory factor (GRIF). PMID- 6248792 TI - Electrochemical, photoelectrochemical, electrocatalytic and catalytic reduction of redox proteins. AB - Redox proteins catalyse the reactions of a wide variety of otherwise intractable substrates, such as dinitrogen, alkanes, arenes, terpenes and steroids. Two major factors impede the utilization of these enzymes--the inefficient electron transfer between the enzyme and electrode, and the properties often, but not inevitably, associated with enzymes, such as instability, complexity, and expense. We have now shown that the former can be overcome and that proteins can be coupled, via electrodes, to a number of energy sources; the latter is the subject of much effort elsewhere. We demonstrated previously that certain redox proteins can be reduced very efficiently electrochemically (Fig. 1a). Light and hydrogen are the two other convenient energy sources that could be used for such reductions, and we now report the reduction of cytochrome c by these means. PMID- 6248793 TI - Extra-pituitary actions of LHRH and its agonists. PMID- 6248794 TI - Comparison of white pock (h) mutants of monkeypox virus with parental monkeypox and with variola-like viruses isolated from animals. AB - Monkeypox mutants arising spontaneously or after serial, high multiplicity passage were characterized phenotypically and by restriction endonuclease mapping. Some resemble "whitepox" and variola viruses in several of the markers tested but all are distinguishable phenotypically from these. None resembles "whitepox" viruses in genome structure although near-terminal deletions or symmetrical, terminal rearrangements, relative to parental monkeypox, occurred. "Whitepox" viruses isolated from animals closely resemble variola in both phenotype and genome structure. PMID- 6248795 TI - Single acetylcholine-activated channels show burst-kinetics in presence of desensitizing concentrations of agonist. AB - High resolution measurements of the current through individual ion channels activated by acetylcholine (AChR- channels) in frog muscle have shown that these currents are discrete pulse-like events with durations of a few milliseconds. Fluctuation and relaxation measurements of end-plate currents have led to the conclusion that the rate of channel opening increases with agonist concentrations, and that the channel, once open, closes spontaneously. Katz and Thesleff have shown, however, that in the continued presence of ACh, the initial end-plate current declines to an equilibrium value with a time constant of several seconds. This reversible phenomenon is referred to as receptor desensitization. We report here that in the presence of ACh concentrations sufficient to cause desensitization, single channel current pulses appear in groups. From the temporal sequence of the pulses, we have derived estimates of the rates of activation and desensitization of the AChR-channel. PMID- 6248796 TI - The insulin gene is located on chromosome 11 in humans. PMID- 6248797 TI - 3H-Prazosin binds specifically to 'alpha 1'-adrenoceptors in rat brain. AB - Prazosin is know to block postsynaptic alpha-adrenoceptors. In this study 3H prazosin has been used to label biochemically central alpha-adrenoceptors. In rat brain membranes 3H-prazosin bound specifically in a rapid, reversible and saturable manner to a single class of high affinity sites. The relative order of potencies for inhibition of 3H-prazosin binding was WB4101 greater than ARC 239 greater than phentolamine greater than piperoxane greater than yohimbine which is a characteristic of the alpha 1 type of adrenoceptors. In contrast, the relative order of potencies for inhibition of 3H-clonidine binding was yohimbine greater than piperoxane greater than WB4101 greater than ARC239 greater than prazosin which is a characteristic of the alpha 2 type of adrenoceptors. These results indicate that 3H-prazosin binds to central 'alpha 1'-receptors and 3H-clonidine to 'alpha 2'-receptors and confirm the presence of two classes of alpha adrenoceptors in rat brain membranes. PMID- 6248798 TI - Central blood pressure effects of guanylyl-imido-diphosphate and cyclic guanosine monophosphate. AB - Injections of guanylyl-imido-diphosphate (250, 500 and 1,000 microgram/kg) into the lateral cerebral ventricle of the anaesthetized cat induced increases in blood pressure and heart rate while the intravenous injections of the same doses were ineffective, thus indicating a central mechanism of action of this compound which activates adenylcyclase at the catalytic subunit. The results support the hypothesis that the activity of cardiovascular centres depends on the prevailing concentration of cAMP. Intracerebroventricular injection of cGMP (125, 250 and 500 microgram/kg) caused hypotension and bradycardia. The effects increased with the dose but were subject to tachyphylaxis. The lack of an effect after intravenous administration indicates a central site of action. This result is in agreement with the Yin Yang hypothesis and suggests that cGMP is a second transmitter in cardiovascular centres which may be involved in central cardiovascular effects in response to stimulation by putative neurotransmitter substances such as acetylcholine. PMID- 6248799 TI - Stimulation by adrenaline and dopamine but not by noradrenaline of myocardial alpha-adrenoceptors mediating positive inotropic effects in human atrial preparations. AB - In isolated electrically driven right auricular strips of human hearts (1 Hz at 37 degrees C) the ability of the endogenous catecholamines noradrenaline, adrenaline, and dopamine to mediate positive inotropic effects by stimulation of myocardial alpha-adrenoceptors was investigated. 1. The concentration-response curve for the positive inotropic effect of noradrenaline was shifted to the right by pindolol, 10(-8)M, whereas the additional blockade by phentolamine, 3 x 10( 6)M, was without further effect; therefore, the positive inotropic effect of noradrenaline is mediated by beta-adrenoceptors only. 2. In contrast, the positive inotropic effects of adrenaline as well as of dopamine are caused by stimulation of both, beta- and alpha-adrenoceptors. 3. These results are discussed with respect to the possible physiological and pathophysiological function of myocardial alpha-adrenoceptors. PMID- 6248800 TI - Characterization of tumors induced in adult Macaca mulata monkeys with Carr Zilber strain of Rous sarcoma virus. AB - The Carr-Zilber strain of Rous sarcoma virus is highly oncogenic for adult monkeys of the species Macaca mulata. In the present study, we examined some characteristics of tumor growth when the tumor either regressed or progressed until it killed its host. We followed the kinetics of antibody formation to antigens coded by CZ-RSV in animals with a different course of tumor disease. The sera of animals tested contained virus-neutralizing antibodies, in addition to gs antibodies. The results are discussed with regard to the possible virus productive type of interaction between RSV and the monkey cell. PMID- 6248801 TI - Neoplastic growths in chickens treated with cell and cell-free material from transplantable hepatoma induced by virus strain MC-29. AB - Series of experiments were carried out with chickens (line 15-I and Canadian white leghorn) for establishing the oncogenic properties of Mc-29 virus strain after its multiple replication in cells transformed by it (hepatoma cells). It was established that: 1. After s. c. and i. m. inoculation of intact hepatoma cells local hepatomas of varying size developed after 8--15 days accompanied with general viremia; after i. p. or i. v. injection multiple hepatoma growths occurred in the visceral organs and bone marrow. 2. The i. v. or i. p. inoculation of cell-free material of hepatoma or blood plasma of hepatoma bearing chicken lead after 48--80 days to the formation of hemocytoblastic and myelocytoma growths in the visceral organs and in the bone marrow and exclusively rare--of primary liver and kidney carcinomas. After s. c. injection of cell-free material the result is negative. A conclusion could be drawn that strain Mc-29 virus though replicated in the transformed hepatoma cells preserved its basic leukemogenic potentialities to induce myelocytomatosis and hemocytoblastosis and very rarely--liver and kidney carcinomas. PMID- 6248803 TI - [Metastatic tumors in the central nervous system. The neuropathological point of view (Part 1) (author's transl)]. PMID- 6248802 TI - Physicochemical approaches to the alcohol-membrane interaction in brain. AB - The effects of ethanol on physicochemical and enzymatic perturbations of neuronal membranes were examined. Using synaptic plasma membrane (SPM) isolated from cerebral cortex of Sprague-Dawley rats, a biphasic mode of action for ethanol was observed with (Na+ + K+)-ATPase, but not with Ca2+-ATPase or acetylcholinesterase. (Na+ + K+)-ATPase was found to be more sensitive to low concentration of sodium deoxycholate treatment than Ca2+-ATPase. A sharp transition break of (Na+ + K+)-ATPase activity in response to temperature changes was found with SPM preparation. Arrhenius plots of the response also indicated that (Na+ + K+)-ATPase is more sensitive to temperature changes than Ca2+-ATPase. The fluorescence polarization of TNS-membrane complex decreases as ethanol concentration increases, indicating an increase in membrane fluidity. However, ethanol, at low concentration (less than 0.3%) appears to elevate TNS fluorescence, but at higher concentration (3%) ethanol tends to lower the intensity of maximal emission. The results of this study indicate that ethanol may interact with the synaptic plasma membranes and elicit specific biochemical responses depending on the concentration of the alcohol used. PMID- 6248804 TI - [A case of metastatic adenoid cystic carcinoma in left cerebellar hemisphere (author's transl)]. PMID- 6248805 TI - Compensatory adrenal growth in immature and mature male rats. AB - We measured adrenal weights 3 days after left- or sham-adrenalectomy in male Sprague-Dawley rats at 10 ages between 10 and 155 days. Compared to sham-operated rats, the magnitude of the increase in right adrenal weight ranged between 19 and 32% after unilateral adrenalectomy and was significant at 10, 20, 40, 50, and 60 days (p less than 0.01). Comparing left with right adrenals in unilaterally adrenalectomized rats, the right was heavier at all ages (p less than 0.01); in animals 40 days and younger, this is due to normal adrenal growth rate (0.3 mg/day) as well as compensatory adrenal growth, while in older animals normal growth rate is slow (0.04 mg/day) and this difference in left and right adrenal weights is due primarily to compensatory growth. We conclude from this study that compensatory adrenal growth occurs 3 days after left adrenalectomy at all ages except 15 and 30 days. Resting levels of plasma ACTH and corticosterone did not differ between left- and sham-adrenalectomized rats at any age. The ACTH response to 1 min exposure to ether vapors was markedly reduced in 7- and 12-day-old rats (p less than 0.01). We conclude that compensatory adrenal growth is a consistent response 3 days after unilateral adrenalectomy that depends neither on the age at which surgery is performed nor on the capacity of the rat to secrete markedly elevated levels of ACTH. PMID- 6248806 TI - Extrahypothalamic corticotropin and alpha-melanotropin in human brain. AB - The distribution of corticotropin (ACTH) and alpha-melanotropin (alpha-MSH) in human brain was investigated by radioimmunoassay using an antiserum which recognized h-ACTH1-39 and alpha-MSH to an equal degree on a molar basis. Significant amounts of material, which migrated on calibrated Sephadex G-50 columns as synthetic h-ACTH1-39 and synthetic alpha-MSH, were detected in distinct brain areas. The highest concentrations of ACTH and alpha-MSH were found in the diencephalon (hypothalamus 4.2 and 12.5 pmol/g wet weight, respectively) and in midbrain (periaqueductal gray 0.5 and 1.7 pmol/g, respectively) and smaller quantities in the rhombencephalon and telencephalon. The ACTH concentration in human pituitary (adenohypophysis) was 10(4)-fold greater than that in the hypothalamus. alpha-MSH was confined to the midpart and/or stalk region of the pituitary. PMID- 6248808 TI - Sites at which clonidine acts to affect blood pressure and the secretion of renin, growth hormone and ACTH. AB - To further define the sites in the brain at which clonidine acts to lower blood pressure, inhibit renin secretion, inhibit ACTH secretion, and stimulate growth hormone secretion, small doses of this drug were infused into the vertebral arteries, into the carotid arteries and intravenously in pentobarbital anesthetized dogs. Because injections of radioactive microspheres demonstrated that vertebral blood reached the hypothalamus, intravertebral and intracarotid infusions were also carried out after occlusion of the basilar artery in the midpontine region. Intracarotid clonidine, 2 microgram/kg, decreased plasma ACTH and corticoids and increased plasma growth hormone, whereas the same dose had no effect on these hormones when given intravenously or when given intravertebrally after occlusion of the basilar artery. Intravertebral clonidine lowered blood pressure to a greater degree than intracarotid and intravenous clonidine. The reduction in heart rate produced by clonidine was essentially the same whether the drug was administered via the intravenous, intracarotid, or intravertebral route. Intracarotid and intravertebral clonidine decreased plasma renin activity whereas in this dose intravenous clonidine did not. However, there was no renin response to intracarotid and intravertebral clonidine when the basilar artery was occluded. The data support the conclusion that clonidine acts rostral to the pons to decrease ACTH secretion and increase growth hormone secretion, whereas it acts on the medulla or adjacent hindbrain to lower blood pressure. In the dose used, clonidine appears to affect heart rate by a peripheral rather than a central action. The data confirm the observation that clonidine acts on the brain to inhibit renin secretion, and establish that the renin-inhibiting site is different from the blood pressure-lowering site. However, they do not permit localization of the renin-lowering site within the brain. PMID- 6248807 TI - Maturation of adrenal stress responsiveness in the rat. AB - Serum and adrenal corticosterone was measured by competitive protein-binding radioassay in rats subjected to saline injection, ACTH administration or ether fumes. Groups of rats were tested at 5, 7, 9, 11, 13, 15, 20 and 25 days of age and measurement of hormone level was made either before treatment, to obtain basal values, or 15 min after treatment. Furthermore, the time-course of corticosterone release after ether was determined in 9- and 15-day-old rats. Neonatal rats responded to ether exposure, ACTH administration or saline injection with a significant rise in serum and adrenal corticosterone concentration above basal levels as early as 5 days of age. By 9 days of age, response to stress was qualitatively the same as that of the 25-day-old rat. The time course of adrenal responsiveness to ether stress was similar in 9- and 15 day-old rats, both age groups showing significant increases in hormone concentration by 15 min. These results contradict the concept of the 'stress non responsive period' which was promoted by previous studies based on the fluorometric analysis of corticosterone. PMID- 6248809 TI - Effects of systemically administered indomethacin on basal and stress-induced ACTH and corticosterone secretion in the male rat. AB - The effects of the prostaglandin (PG) synthetase inhibitor indomethacin (IM) on basal and stress-induced activity of the hypothalamo-hypophyseal-adrenal (HHA) axis were investigated. IM was systemically administered to adult male rats in a single injection (5 mg/100 g BW s.c.). The animals were sacrificed 24 h later, either under basal conditions, or following 30 min exposure to environmental temperature of 36 degrees C. Serum ACTH and corticosterone (CS) were determined by RIA and CBG, respectively, and hypothalamic and adenohypophyseal PGE2 and total PGE concentrations were estimated by RIA. IM treatment resulted in elevated basal levels of both hormones. Heat exposure led to elevated serum ACTH and CS concentrations in both vehicle- and IM-treated groups, with the ACTH heat response in IM-treated animals being greater than that observed in controls. PGE2, and PGE1 plus PGE2 concentrations were markedly reduced in both hypothalamic and adenohypophyseal tissues, following IM treatment. This study demonstrates that simultaneous reductions in hypothalamic and adenohypophyseal PG concentrations are compatible with hyperactivity of the HHA axis. PMID- 6248810 TI - Analgesia and ptosis caused by caerulein and cholecystokinin octapeptide (CCK-8). PMID- 6248811 TI - The effect of psychoactive drugs on beta-adrenergic receptor binding sites in rat brain. PMID- 6248812 TI - Granular cell tumor of the pituitary gland associated with diabetes insipidus. AB - A hypophysectomy was performed for palliation of metastatic carcinoma of the breast in a 62-year-old woman who also had diabetes insipidus. At operation a neurohypophyseal mass was discovered; it proved to be a granular cell tumor. The diabetes insipidus resolved postoperatively. PMID- 6248813 TI - Quantitative characterization of the ultrastructural changes in axo-dendritic synapses induced by tetanus toxin. PMID- 6248814 TI - Some mechanisms of hypothalamo-hypophysio-adrenal disturbances in Itsenko Cushing's disease. PMID- 6248815 TI - Binsing studies with muscimol; relation ty synaptic gamma-aminobutyrate receptors. PMID- 6248816 TI - Extraneuronal catecholamine in the iris of the rat: a consequence of nonsynaptic neurotransmission? PMID- 6248817 TI - Carbonic anhydrase and 2',3' cyclic nucleotide 3'-phosphohydrolase activity in normal human brain and in demyelinating diseases. AB - The activities of carbonic anhydrase and 2',3' cyclic nucleotide 3' phosphohydrolase (CNPase) were measured in gray and white matter and in myelin from human brains obtained at autopsy. Carbonic anhydrase activity increased with age, and at all ages a major part of the activity was associated with membrane fractions. The percentage of membrane-bound carbonic anhydrase was lower than normal in white matter from Krabbe disease and adrenoleukodystrophy; isolated myelin had a low specific activity in these diseases. CNPase activity was decreased in both white matter and myelin, but was somewhat higher than normal in gray matter. Although the yield of myelin from a case of metachromatic leukodystrophy was markedly reduced, changes in the enzymes activities were minimal. PMID- 6248818 TI - Immunosuppressive drugs in multiple sclerosis: pro and con. PMID- 6248819 TI - Possible beneficial effect of high-dose intravenous steroid therapy in acute demyelinating disease and transverse myelitis. AB - Intravenous steroid followed by oral prednisone was administered to patients with Guillain-Barre syndrome (five), acute transverse myelitis (three), and multiple sclerosis in acute relapse (seven). Preliminary experience with each of these disorders revealed prompt clinical improvement in some patients. The approach used in this uncontrolled study deserves further investigation. PMID- 6248820 TI - Problems in evaluating new treatments for multiple sclerosis. AB - There are multiple difficulties in evaluating new treatments for multiple sclerosis (MS). The clinical diagnosis is imprecise, and the correlation between lesion and clinical dysfunction is incomplete. The neurologic evaluation is complex and lacks full precision. The course of MS is complex and has limited predictability. There is no laboratory test that can be accepted now as compensating for the defects in diagnosis, lesion-symptom correlation, course, and neurologic evaluation. Because of these problems, which appear inherent in MS, there are limitations to the statistical methods that can be properly applied to trials of therapy. Most trials of definitive nature will require a random design. When improvement is seen in a trial of therapy, there may be difficulty in determining the mechanism. PMID- 6248821 TI - Multiple sclerosis and viruses: an overview. AB - The evidence for a viral etiology of MS has been reviewed. The strongest evidence favoring a virus is based primarily on epidemiologic considerations. Less convincing evidence comes from pathologic studies, serology, lymphocyte reactivity to viral antigens, and reports of identification of virus in MS tissues. Animal models of viral demyelination exist, which may provide insight into possible etiologic agents and pathogenetic mechanisms. Considering all the data, it is clear that no agent can be convincingly linked to MS at the present time. If a single virus causes the majority of cases of MS, then a morbilliform virus--canine distemper--is a leading contender, because this agent is consistent with the epidemiologic and serologic findings and is highly neurovirulent for animals ranging from mice to primates. Since no virus fulfills the usual criteria for linking an infectious agent to a disease, other possibilities must be considered. If MS is caused by a single virus, it may be a common virus not presently considered as being associated with MS, or an agent as yet unidentified. It is also conceivable that multiple agents, acting alone or in concert, initiate the MS process, perhaps through a common immune-mediated pathway. In this regard, another human demyelinating disease--the Guillain-Barre syndrome--which may in some instances become a chronic remitting and relapsing disorder, is thought to be initiated by multiple infectious agents but to have an immunologic pathogenesis. PMID- 6248822 TI - [Fuso-cellular carcinoma of the esophagus with aspects of microcytoma (oat cell)]. AB - A case of polypoid carcinoma of the lower oesophagus in a 52 yr old man is reported. The tumour presented the histological features of spindle-cell squamous carcinoma and oat-cell carcinoma. The histogenesis of these tumours is considered. PMID- 6248823 TI - [Clinical trial of a new broad-spectrum cephalosporin: HR 756 (cefotaxime)]. AB - A second-generation cephalosporin (cephotaxime) with a marked resistance to beta lactamase, a very broad spectrum, and remarkably low renal toxicity was used to treat 47 patients with respiratory, urinary and other infections. The results were excellent in 89.2% and good in 8.5%. The antibiotic proved effective even against germs that are usually resistant to cephalosporins (Pseudomonas, Proteus, Serratia and Enterobacteriaceae). Bacteriuria disappeared in all cases of urinary infection. Local and general tolerance was excellent in all cases but one. Renal tolerance was also excellent in patients with chronic renal failure, for whom the daily dose can be usefully reduced and a check on renal function should be kept. PMID- 6248824 TI - [Cellular membranes: synthesis of the "second messengers"]. PMID- 6248825 TI - Fatal Clostridium perfringens sepsis; following malignant hemangioendothelioma of scalp. PMID- 6248827 TI - Prosthetic replacement of bilateral maxillectomy. AB - A patient had an adenocystic carcinoma that involved both maxillary sinuses, the entire hard palate, and the lower third of both nasal chambers. Treatment consisted of bilateral maxillectomy and a split-thickness skin graft applied to the inside of the cheeks. A dental obturator constructed to fit undercuts in the surgical cavity allowed speech and swallowing. Because the patient objected to the sunken appearance of the upper lip, she obtained the central incisor portion of her late husband's upper denture and bonded this segment to the dental appliance. This achieved satisfactory cosmesis. PMID- 6248826 TI - [Malignant tumors of the ear treated at the 1st Otolaryngologic Clinic of the Slask Medical Academy from 1967 to 1977]. PMID- 6248828 TI - Immunoglobulin A antibody to Epstein-Barr viral antigens and prognosis in nasopharyngeal carcinoma. AB - IgA immunoglobulin fractions containing antibodies to Epstein-Barr virus (EBV) induced membrane antigens were isolated from the sera of two patients with nasopharyngeal carcinoma (NPC), from one non-NPC patient, and from three persons with sera negative for IgA antibodies. IgA antibodies were not cytotoxic against cells expressing EBV-induced membrane antigens in the antibody-dependent cellular cytotoxicity (ADCC) assay. However, IgA antibodies blocked IgG-mediated ADCC, which indicated that these antibodies could serve as a blocking "factor" in patients with disease and, therefore, were potentially detrimental to the host. PMID- 6248829 TI - Management of the more common pediatric neoplasms with particular reference to Hodgkin's and non-Hodgkin's lymphoma, Wilms' tumour and neuroblastoma. AB - Accurate pathological diagnosis and staging of extent of disease are key steps in the management of childhood neoplasms. Adjuvant chemotherapy is responsible for improved survival rates. In non-Hodgkin's lymphoma intensive chemotherapy, irradiation to areas of bulk disease and central nervous system prophylaxis are combined in treatment. Chemotherapy and limited field irradiation have improved survival in Hodgkin's disease. Treatment varies widely in neuroblastoma according to stage with disseminated disease still carrying a very poor prognosis. Survival in Wilms' tumour has improved to such an extent that long-term side-effects of therapy now need to be considered. PMID- 6248830 TI - Sub-cellular fractionation of Trypanosoma brucei. Isolation and characterization of plasma membranes. AB - A procedure is described for the isolation of sub-cellular fractions from bloodstream forms of Trypanosoma brucei. The method leaves intact most of the nuclei, mitochondria and microbodies. All the fractions have been chemically characterized and tested for 10 enzymatic markers. About 5% of total cell protein was isolated as a microsomal fraction containing mostly plasma membranes and endoplasmic reticulum vesicles. Plasma membranes were purified by high-speed centrifugation on magnesium-containing Dextran, and on linear sucrose-density gradients. The yield of membranes was approximately 0.3% of the total cell protein. The purified material had a sucrose density of 1.14 g/cm3 and consisted of smooth vesicles. Specific activity of the membrane markers Na+, K+, ouabain sensitive ATPase and adenylate cyclase were 26- and 20-fold higher, respectively, than in total cells. Neither DNA nor RNA was detected. The sum of the cholesterol and phospholipid content was 0.99 mg/mg protein. The cholesterol/phospholipid molar ratio was 1:2. PMID- 6248831 TI - [Pathophysiologic and therapeutic significance of cyclic nucleotides]. PMID- 6248832 TI - [Bronchial adenoma--comparison of the cytological and histological pictures]. PMID- 6248833 TI - [Generalized cytomegalic diseases in the newborn infant. Presentation of a case]. PMID- 6248834 TI - Solitary spinal metastasis from Wilms' tumor. AB - A 7 year old boy presented with sudden lower extremity paresis six months after resection of a Wilms' tumor. Roentgenologic studies showed destruction of the sixth vertebral body and a thoracic extradural block by an epidural mass subsequently proven to be a solitary Wilms' metastasis. PMID- 6248835 TI - [Immunovirological studies in children with Hodgkin's disease]. PMID- 6248836 TI - [Effect of infusion-anabolic therapy on protein metabolism in children with nephroblatoma in the postoperative period]. PMID- 6248837 TI - Response of central vestibular neurons to horizontal linear acceleration in the rat. AB - Responses of central vestibular neurons to horizontal sinusoidal translation (F:0.25Hz) were recorded in albino rat. 57.5% of vestibular neurons were responding to this stimulation by a modulation of their firing rate, the mean phase angle of the response, averaged from the whole population being 22 +/- 79 deg. lag, relative to the peak of contralateral acceleration. Dynamic characteristics of phase and gain were studied and appeared to be different from previous reports on primary afferents: the gain decreased or was flat with increasing acceleration at one frequency, and the phase lag which was flat in the same conditions increased with increasing frequency. A phase lead of some units has been observed at low frequency (0.1 Hz). Regarding the convergence between otolith and canal inputs on nuclear vestibular neurons, it was shown that the major pattern of convergence is between canal and otolith inputs of same polarity. PMID- 6248839 TI - [Value of gastrofibroscopy in present-day diagnosis and treatment of stomach neoplasms]. PMID- 6248838 TI - On the mechanism of slow calcium channel block in heart. AB - 1. D600 (methoxyverapamil, 2 x 10(-6) M) has little activity when it is applied during a rest interval. Its ability to depress Isi and contraction is much reduced when the muscle is rested. 2. Upon each activation the blockade of the slow channel increases until the use-dependent increase of blockade equals the diastolic removal, thus resulting in a frequency-dependent steady-state blockade. 3. Removal of block during a variable rest interval at various holding potentials is the faster the more negative the holding potential and gets slower in the more positive and gets slower in the more positive potential range. This process can be described by two voltage-dependent time constants (tau 1, tau 2). Similarities in the action of D600 on the si-channel to the action of local anaesthetics on the Na+-channel in nerve and heart are pointed out. PMID- 6248840 TI - Arthritis associated with common viral infections: mumps, coxsackievirus, and adenovirus. AB - Arthritis complicating the common viral infections--mumps, coxsackievirus, and adenovirus--can be enigmatic. Mumps arthritis is often difficult to identify, especially when parotitis is mild, because the arthritic syndrome generally follows complete clearing of salivary adenitis by one to two weeks. Migratory polyarthritis is common and may run a protracted course, but only supportive care is generally needed. Arthritis associated with coxsackievirus or adenovirus infection may be particularly perplexing, as the dominant syndrome may be a classic Still's variety of juvenile rheumatoid arthritis. The polyarthritis may be persistent and/or recurrent, despite administration of potent antiinflammatory agents. PMID- 6248841 TI - Small cell carcinoma of the lung. AB - Over a 5-year period 230 cases of small cell carcinoma presented to Brompton Hospital, London. The male to female ratio was 2.5:1 and 39% had evidence of extrathoracic disease. Forty-five patients were untreated and had a median survival of 70 days. The 5-year survival for surgery and radiotherapy was 6.6% and 4.2% respectively. Of 13 patients treated with chemotherapy the median survival was 285 days. The factors which influence survival are described. PMID- 6248842 TI - An isolated right hypoglossal nerve palsy in association with infectious mononucleosis. AB - Following an upper respiratory tract infection, a teenage girl developed an isolated right XII nerve palsy; subsequently she was shown to have infectious mononucleosis. After 24 weeks her tongue had virtually recovered. PMID- 6248843 TI - Unusual presentation of cholangiocarcinoma. AB - A patient who presented with dysphagia was found to have a cholangiocarcinoma, with metastases in the para-oesophageal lymph nodes. Although dysphagia has been described as a presenting feature of some metastatic carcinomas, to the authors' knowledge, there have been no reports of it as a presenting symptom of a cholangiocarcinoma. PMID- 6248844 TI - Opiate receptors, endorphins and drug therapy. AB - A number of opioid peptides isolated from brain and peripheral tissue have been identified, and several types of opiate receptor postulated for these endogenous substances. In this study the effects of pharmacological manipulation of 5 hydroxytryptamine (5-HT) on the antinociceptive activity of morphine and two synthetic enkephalin analogus (D-ala2-leu-enkephalin and D-ala2-met-enkephalin) were investigated in mice and rats. Centrally injected 5-HT and peripheral clomipramine pretreatment potentiated both morphine and synthetic enkephalin analgesia whilst peripheral doses of cyproheptidine, lesions in the dorsal medial raphe (DMR) and reserpine pretreatment attenuated opioid analgesia. In the reserpine-pretreated group, centrally injected 5-HT restored the antinociceptive activity of morphine and D-ala2-leu-enkephalin. These results are discussed with respect to clomipramine therapy. PMID- 6248845 TI - A possible cyclic adenosine monophosphate stimulation test in depression. AB - Changes in cyclic adenosine monophosphate (cAMP) excretion and/or endocrine function in some depressed patients suggest that a cAMP stimulation test might be of value in predicting individual responses to antidepressant therapy. PMID- 6248846 TI - The interrelationship between hormones, psychotropic drugs and the opiate receptor--a pilot study. AB - Earlier reports had shown pronounced effects of clomipramine on plasma pituitary and gonadal hormone levels. In a continuation of these studies no change could be seen in rat plasma corticosterone levels following long-term, toxic administration of the drug despite a marked adrenal hyperplasia. It had been suggested that the action of clomipramine might be potentiated through the opiate receptor. Initial experiments using a rat model system have shown that morphine increased plasma prolactin and reduced plasma luteinizing hormone levels in vivo and that these effects could be overcome by naloxone. No direct effect of enkephalins was observed on rat pituitary organ cultures. The results are discussed in the light of recent findings of the relationship between properties of the opiate receptor and the observed side effects of tricyclic antidepressant therapy. PMID- 6248847 TI - The mode of action of tricyclic antidepressants: a brief review of recent progress. AB - Until recently the tricyclic antidepressants were thought to act by inhibiting uptake of the biogenic amines noradrenaline and 5-hydroxytryptamine (serotonin). But this did not explain why the depressed mood takes several weeks to respond, whereas biogenic amine uptake is inhibited soon after treatment begins. Nor did it explain why some clinically effective antidepressants have little effect if any on biogenic amine uptake. Recent work suggests that changes in receptor sensitivity may be responsible. By the use of radiolabelled, high-affinity, high specificity drugs and receptor-binding assays it is now proving possible to characterize neurotransmitter receptors in greater detail, and this is expected to throw further light on the mechanisms underlying changes in receptor sensitivity. PMID- 6248848 TI - Studies on infectious bursal disease in chickens. 2. Scoring microscopic lesions in the bursa of fabricius, thymus, spleen, and kidney in gnotobiotic and battery reared White Leghorns experimentally infected with infectious bursal disease virus. AB - During a 2 1/2 year study on the effect of experimentally-induced infectious bursal disease (IBD) in White Leghorns, a system for scoring microscopic lesions was developed. Microscopic changes in the bursa of Fabricius, thymus, spleen, and kidney were studied to create a lesion score for each organ. No changes occurred in the cecal tonsil and few, if any, changes occurred in the liver. The system was useful in evaluating the severity of pathologic and inflammatory changes in each organ during the course of the disease. Lesion scores for the bursa ranged from 0 for normal bursae to +4 for severely affected bursae. The lesion scores for the thymus, spleen, and kidney ranged from 0 to +3. The criteria for scoring lesions in the thymus were: 0 equaled no change; +1- cortex had a few empty spaces, pronounced hyperemia with some heterophil infiltration, especially in the medulla; +2- cortex had an increase in the number of empty spaces and increased heterophil infiltration, and the cortex and medulla had decreased hyperemia; +3- cortex had numerous round aggregations (12 to 16 mu in diameter) of cell debris and pyknotic nuclei, a definite decrease in the lymphocyte density in the cortex, and decreased hyperemia in cortex and medulla. This lesion scoring system was useful in determining the severity of IBD in different-aged progeny from IBD immune and nonimmune dams. PMID- 6248849 TI - Targeted deletions of sequences from closed circular DNA. AB - Closed circular DNA interacts with complementary sequences of single-stranded DNA to form displacement loop (D loop) structures in vitro. The site of D-loop formation can be directed by using single-stranded DNA derived from a selected restriction fragment. Circular DNA containing a D loop can then be linearized by cleavage with endonuclease S1. This cleavage appears to remove a limited number of nucleotides from each strand of the circular DNA substrate. Incubation with polynucleotide ligase followed by propagation in vivo leads to circular DNA molecules that bear small, single deletions in the region of the single-stranded DNA sequence chosen for the formation of the D loops. We have utilized these manipulations of DNA to construct tetracycline-sensitive deletion mutants of plasmid pBR322. The level of mutagenesis obtained by the procedure is sufficiently high that selective growth and screening procedures are not necessary for the isolation or identification of mutants. The frequency, variety, and small size of the deletions obtained within the selected target regions present considerable advantage for genetic and biochemical analysis. The method is quite general in rationale and should be immediately applicable to phage and viruses having infectious circular DNA genomes or recombinant DNA species propagated in circular plasmid vectors. PMID- 6248850 TI - Nucleotide sequence of the Salmonella typhimurium origin of DNA replication. AB - Construction of deletion derivative plasmids and cloning of restriction fragments from plasmids containing the Salmonella typhimurium origin of replication (ori) were used to locate the functional origin to within a DNA fragment of 296 base pairs between the genes uncB and asn. The nucleotide sequence of the S. typhimurium ori region was determined and compared with the Escherichia coli ori sequence. In the 296-base pair fragment, 85.8% of the bases are conserved between the two species. A nearly equal number of transition and transversion type differences, with no insertions or deletions, occurs between the two bacterial origins, such that the relatively high percentage (adenine plus thymine) of 59.5% is conserved. The 296-base pair fragment contains 14 GATC sequences, all of which are conserved. The high frequency of occurrence of GATC, which is the site of methylation under control of the dam gene, may explain in part why the bacterial ori region appears to be so highly conserved. A large number of secondary structures are possible. One such structure, with a "cloverleaf," is favored by ori nucleotide sequence comparisons and leads to potential novel macromolecular interactions. PMID- 6248851 TI - Evidence for a "mute" catalytic subunit of cyclic AMP-dependent protein kinase from rat muscle and its mode of activation. AB - An isoenzyme of the catalytic subunit of type II cyclic AMP-dependent protein kinase from rat muscle is reported which coelutes with the classical catalytic subunit but differs from it in isoelectric point (pI 8.7 vs pI 9.1) and is enzymmatically inactive. After reaction with a heat- and acid-stable component of the protein kinase modulator fraction from the same tissue, the "mute" isoenzyme displays a high activity when assayed on isoelectric focusing gels. This activation process does not occur through proteolytic degradation and is not characteristic of a turnover-type reaction. The data imply direct interaction between the isoenzyme and a modulating protein which may subsequently be separated from the enzyme without reversal of the activation. The modulator protein thus appears to act as a template, inducing a conformational change. The implications of such a mute isoenzyme and its control through small modulator proteins are discussed. PMID- 6248852 TI - Fate of donor insertion sequence IS1 during transposition. AB - The number of insertion sequence IS1 segments in Escherichia coli K-12 and 20 mutants in which an ISI had been inserted at a new site was measured by Southern blot hybridization analysis. The parent strain appeared to contain seven IS1 segments. Each of the mutants contained these seven IS1 and one additional IS1 corresponding to the new IS1 insertion. These results suggest that a copy of a donor ISI is inserted at the new site. A model for transposition is prevented that postulates that a reactive intermediate is formed by a tandem duplication of a transposable sequence. PMID- 6248853 TI - Subclasses of external adenosine receptors. AB - Cell surface adenosine receptors mediate either stimulation or inhibition of adenylate cyclase activity [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1], and the receptors that mediate these different responses can be discriminated with selected adenosine analogs. 5'-N-Ethylcarboxamide-adenosine is a more potent agonist at stimulatory receptors (Ra) than is N6-phenylisopropyladenosine, whereas the reverse potency order is seen with inhibitory receptors (Ri). The potency of adenosine is intermediate between the potencies of these two analogs. The relative potencies of adenosine receptor agonists are maintained in physiological responses in intact cells, such as steroidogenesis and inhibition of lipolysis. As with adrenergic receptors, subclasses of adenosine receptors differ functionally and pharmacologically. PMID- 6248854 TI - Genomic integration of bovine leukemia provirus: comparison of persistent lymphocytosis with lymph node tumor form of enzootic. AB - Integration of bovine leukemia proviral DNA in the genome of infected cells was investigated in cattle affected by either the persistent lymphocytosis or the lymph node tumor form of enzootic bovine leukosis. In persistent lymphocytosis, proviral DNA was found to be integrated at a large number of genomic sites in one fourth to one-third of circulating leukocytes. In the lymph node tumor form, in contrast, proviral DNA was found to be integrated at one or very few sites in the genomes of a larger fraction of both circulating leukocytes and lymph node tumor cells. PMID- 6248855 TI - Analysis of the closely linked adult chicken alpha-globin genes in recombinant DNAs. AB - Recombinant bacteriophage (from a library of chicken chromosomal DNA fragments inserted into lambda Charon 4A) have been isolated which contain the coding information for both of the adult chicken alpha-globin genes, alpha A and alpha D. One of these recombinant phage also contains an as yet unidentified embryonic alpha-like globin gene sequence. The two adult genes are encoded on the same DNA strand and are separated by approximately 2.4 kilobase pairs, with the arrangement of the genes relative to the direction of transcription being 5' alpha D-alpha A-3'. Electron microscopic R-loop visualization experiments demonstrate that both alpha-globin genes contain two intervening sequences of similar size in a manner analogous to the structure observed in the mouse alpha globin gene. The linkage of the two highly divergent chicken adult alpha-globin genes further underscores the principle that chromosomal clustering of families of developmentally related genes may be a general phenomenon in higher eukaryotic gene sequence arrangement. PMID- 6248856 TI - Acetate kinase: a triple-displacement enzyme. AB - Facts relating to the mechanism of phosphoryl transfer by acetate kinase (ATP:acetate phosphotransferase, EC 2.7.2.1) are reviewed. They point to the existence of at least one experimentally established phosphoenzyme (E-P) intermediate on the reaction pathway. Sterically, the phosphoryl transfer occurs with a net inversion of the configuration of the phosphorus atom. These facts are best in accord with a triple-displacement mode of action for acetate kinase, with two E-P intermediates and three steric inversions on phosphorus. It follows that a second E-P for acetate kinase must exist. PMID- 6248857 TI - Conformation of the helical nucleocapsids of paramyxoviruses and vesicular stomatitis virus: reversible coiling and uncoiling induced by changes in salt concentration. AB - The conformations of the helical nucleocapsids of the paramyxoviruses Sendai virus and simian virus 5, and of a rhabdovirus, vesicular stomatitis virus, have been found to vary extensively with changes in salt concentration. In 10 mM sodium phosphate buffer at pH 7.2, the nucleocapsids are loosely coiled or almost completely extended; with increasing concentrations of NaCl they become more tightly coiled and less flexible. Under isotonic conditions (150 mM) the Sendai virus nucleocapsid is moderately tightly coiled but still curved and apparently flexible, whereas at 400 mM or higher it is very tightly coiled, with the appearance of a rigid rod. These salt-dependent changes in conformation were also found with nucleocapsids composed of proteolytically cleaved protein subunits. Because of the effect of salt concentration, and the fact that it may change during the preparation of negatively stained samples of electron microscopy, it was necessary to fix that nucleocapsids before negative staining to preserve their original conformation. The striking changes in nucleocapsid conformation in response to the ionic milieu indicate the plasticity of its helical structure and suggest that changes in the microenvironment of the nucleocapsid could influence its conformation during viral RNA transcription and replication or during virus assembly by budding, processes in which changes in the coiling of the nucleocapsid or its flexibility could be important. PMID- 6248858 TI - Identification and molecular cloning of Moloney mouse sarcoma virus-specific sequences from uninfected mouse cells. AB - When uninfected mouse cell DNA is cleaved with restriction endonuclease EcoRI, a DNA fragment of 14.0 kilobases can be identified by hybridization to cloned DNA containing sarcoma specific sequences of Moloney mouse sarcoma virus (M-MSVsrc). The cellular DNA fragment contains the entire M-MSVsrc specific sequences. The 14.0-kilobase EcoRI DNA fragment was cloned in bacteriophage lambda. The sequence organization of a recombinant clone, lambda . MTX-1, was analyzed by restriction endonuclease mapping, nuclease S1 mapping, and electron microscopy. The results indicate that lambda . MTX-1 contains an uninterrupted stretch of 1.0 kilobase similar to that found in the M-MSV genome. PMID- 6248859 TI - Steady-state properties of coupled systems in mitochondrial oxidative phosphorylation. AB - At steady state there is effective coupling among various otherwise independent membrane and internal mitochondrial systems that share the same substrates or ligands (e.g., H+, Ca2+, Pi, ADP, ATP). The number of different systems, coupled through shared substrates or ligands, is no doubt very large. But, just as an infinite series can be approximated by a finite number of terms, here the number of systems included in the analysis can be limited, as an approximation. In two previous papers, the basic but oversimplified set of four tightly coupled systems was studied. These are: respiratory chain; reverse ATPase; proton-phosphate cotransport; and ADP-ATP exchange. Essentially as illustrations of the methodology required for a more realistic analysis, two much more complicated examples are formulated here: eight tightly coupled systems, and the original four systems but with the tight coupling relaxed in two of these four. PMID- 6248860 TI - Ascorbic acid inhibits replication and infectivity of avian RNA tumor virus. AB - Ascorbic acid, at nontoxic concentrations, causes a substantial reduction in the ability of avian tumor viruses to replicate in both primary avian tendon cells and chicken embryo fibroblasts. The virus-infected cultures appear to be less transformed in the presence of ascorbic acid by the criteria of morphology, reduced glucose uptake, and increased collagen synthesis. The vitamin does not act by altering the susceptibility of the cells to initial infection and transformation, but instead appears to interfere with the spread of infection through a reduction in virus replication and virus infectivity. The effect is reversible and requires the continuous presence of the vitamin in the culture medium. PMID- 6248861 TI - Anion channel blockers inhibit lysosomal enzyme secretion from human neutrophils without affecting generation of superoxide anion. AB - The role of permeant anions in lysosomal enzyme secretion from human neutrophils was investigated by means of anion-channel-blocking agents: 4,4' diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), 4-acetamido-4' isothiocyanostilbene-2,2'-disulfonic acid (SITS), and pyridoxal phosphate. Lysosomal enzyme release from cytochalasin B-treated human neutrophils stimulated by immune complexes (bovine serum albumin and IgG anti-bovine serum albumin) was inhibited by DIDS, SITS, and pyridoxal phosphate at concentrations that inhibited sulfate fluxes. Enzyme secretion triggered by calcium ionophore A23187 was also inhibited by DIDS and SITS; these agents acted on secretory events subsequent to Ca2+ influx. Neither the species of permeant anion(s) nor the role of anion fluxes in degranulation was identified, although influxes of chloride, hydroxide, or phosphate ions were not critical. In contrast to degranulation, generation of superoxide anions (O2.-) stimulated by immune complex or A23187 was not inhibited by these agents. Ultrastructural cytochemical studies demonstrated that, although lysosomal contents were not discharged from stimulated cells, vacuole formation and lysosome-lysosome fusion were unaffected by SITS or DIDS. Data suggest that anion channel blockers specifically inhibit fusion of lysosomes with the plasma membrane or its invaginations. PMID- 6248862 TI - Establishment of a fetal rat liver cell line that retains differentiated liver functions. AB - Fetal rat liver cells were transformed with a temperature-sensitive A mutant (tsA255) of simian virus 40. A CLONAL CELL LINE, RLA255-4, which was temperature sensitive in the maintenance of the transformed phenotype, was isolated. This cell line expressed the transformed phenotype (rapid growth, high cell density, overgrowth of normal cells, and cloning in soft agar) at the permissive temperature (33 degrees C) and the nontransformed phenotype (slower growth, lower saturation density, decreased efficiency of overgrowth of normal cells, and lower cloning efficiency in soft agar) at the restrictive temperature (40 degrees C). The tsA255-transformed cells expressed differentiated liver functions under controllable conditions. At the permissive temperature, they produced low levels of albumin and transferrin, whereas at the restrictive temperature the transformed phenotype was lost and the production of these hepatic proteins was greatly enhanced. RLA255-4 cells contained functional receptors for glucagon, as shown by the stimulation of intracellular cyclic AMP accumulation by glucagon. The response to glucagon was dose dependent (Kact = 5 x 10(-8) M) and could be demonstrated in cells grown at both permissive and restrictive temperatures after 7 days in culture (i.e., at a cell density of approximately 4 x 10(5) cells per cm2 or higher). Addition of cortisol to the culture medium enhanced the glucagon response selectively at the restrictive temperature. PMID- 6248863 TI - Epidermal growth factor-induced down-regulation of receptor does not occur in HeLa cells grown in defined medium. AB - 125I-Labeled epidermal growth factor (EGF) binds to HeLa cells in culture under completely defined conditions in a specific and saturable manner. When the cultures are maintained in serum, all the reported phenomena of down-regulation occur. In contrast, in cultures maintained in serum-free hormone-supplemented medium, binding is maximal after 50 min and remains constant for at least 18 hr. EGF retains its mitogenic activity in this defined system; as little as 4 pM EGF elicits a 2-fold increase in cell number in 5 days. EGF appears to be in reversible equilibrium with a constant number of surface receptors, and gel filtration analysis indicates a decrease in the rate of degradation and release of bound 125I-labeled EGF. These results indicate that EGF can retain its mitogenic activity in the absence of concomitant down-regulation. PMID- 6248864 TI - Control of guinea pig intestinal electrolyte secretion by a delta-opiate receptor. AB - The effects of opioids on transepithelial potential difference and short-circuit current across guinea pig ileum stripped of one muscle layer were measured in vitro in Ussing chambers. Opioid peptides such as [DAla2, DLeu5]enkephalin and [DAla2, DMet5]enkephalin, which are primarily agonists at delta-opiate receptors, were able to reduce transepithelial potential difference and short-circuit current at concentrations as low as 1 nM. The narcotic drug etorphine was also very potent in reducing short-circuit current, but fentanyl and morphine, which are primarily agonists at mu-opiate receptors, were almost completely ineffective. Ketocyclazocine was relatively ineffective, and beta-endorphin had intermediate potency. All opioid effects could be reversed by the opiate antagonist naloxone. Somatostatin also reduced short-circuit current, but its effect was not reduced by naloxone. Chloride flux measurements indicated that the effect of etorphine on short-circuit current is associated with an enhancement of active Cl- absorption. The relative effects of opioids in this system suggest that their actions are being mediated by a specific delta-opiate receptor. In contrast, opioid effects on guinea pig intestinal smooth muscle seem to be primarily mediated by a mu-opiate receptor. PMID- 6248865 TI - Regulation of ornithine decarboxylase activity by corticotropin in adrenocortical tumor cell clones: roles of cyclic AMP and cyclic AMP-dependent protein kinase. AB - In Y1 adrenocortical tumor cells, corticotropin (ACTH), cyclic AMP, and 8 bromoadenosine 3',5'-monophosphate (8BrcAMP) stimulated ornithine decarboxylase activity (L-ornithine carboxy-lyase, EC 4.1.1.17) and steroidogenesis. The concentrations required for half-maximal activation of ornithine decarboxylase were 60 pM for ACTH and 1 mM for 8BrcAMP; the concentrations required for half maximal activation of steroidogenesis were 50 pM for ACTH and 0.2 mM for 8BrcAMP. Ornithine decarboxylase activity increased 1.5 hr after the addition of these agents, reached a maximum between 4 and 6 hr, and then declined. Mutant clones with impaired ACTH-responsive adenylate cyclase systems [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1]did not respond to ACTH with increased ornithine decarboxylase activity, but they responded normally to added cyclic AMP. These results indicate that adenylate cyclase and cyclic AMP are necessary for the stimulation of ornithine decarboxylase activity by ACTH. In a series of Y1(Kin) mutants with altered cyclic AMP-dependent protein kinase activities (ATP:protein phosphotransferase, EC 2.7.1.37), the effects of ACTH on ornithine decarboxylase also were attenuated. These findings suggest that cyclic AMP-dependent protein kinase also plays a necessary role in the stimulation of ornithine decarboxylase activity by ACTH. The effects of ACTH on ornithine decarboxylase in the Kin mutants, however, were quantitatively different from the effects on steroidogenesis and did not closely reflect the degree of defect in cyclic AMP dependent protein kinase activity. These differences suggest that the pathways of ACTH action leading to stimulation of steroidogenesis and ornithine decarboxylase activity diverge subsequent to activation of the protein kinase. PMID- 6248866 TI - Detection of epidermal growth factor-urogastrone and its receptor during fetal mouse development. AB - Using both a radioimmunoassay and a radioreceptor assay, we have estimated the content of mouse epidermal growth factor-urogastrone (EGF-URO) in fetal mice at 11(1/2) to 17(1/2) days of gestation. Concurrently, the amount of specific EGF URO receptor binding was determined in crude membrane fractions from the embryos. EGF-URO receptor binding is readily detected in membranes from the youngest embryos (day 11(1/2)) and rises steadily up to parturition (18 days); the rise is more marked in embryo membranes derived from a potential target tissue, such as the maxilla and secondary palate. In the embryonic extracts, EGF-URO proved to be labile, requiring the presence of soybean trypsin inhibitor and sodium azide to stabilize the recovery of added EGF-URO in test samples. Even with added stabilizing agents, immunoreactive EGF-URO was barely detectable before day 14(1/2) (less than 20 fmol per embryo), whereas a substantial increase was observed from day 15(1/2) to 17(1/2) (from 70 to 200 fmol per embryo). In contrast, the radioreceptor assay detected appreciable amounts of an EGF-URO-like substance at 11(1/2) days (50 fmol per embryo); the values estimated by radioreceptor assay (about 10-fold higher than by radioimmunoassay) also increase markedly between days 15(1/2) and 17(1/2) (on average from 500 to 3000 fmol per embryo). We conclude that during fetal mouse development there is an increase both in the receptors for EGF-URO and in a substance (presumably a fetal growth factor) that can occupy the receptor. The differences between the radioreceptor and radioimmunoassay estimates for the EGF-URO content suggest that the fetal form of mouse EGF-URO differs from the adult molecule. PMID- 6248867 TI - Selective amplification of variants of a complex repeating unit in DNA of a crustacean. AB - The nucleotide sequence of the repeating unit of a fraction of the highly repetitive DNA of the red crab, Geryon quinquedens, is reported. Treatment of total DNA with HindIII nuclease produced an 81-base-pair monomer and multimers to the size of an octamer. Several of the multimers contained large amounts of fragments of variant sequences, which cannot easily be explained by random mutation alone. That the alterations were not random was corroborated by divergence measurements made on the distribution of Hha I nuclease sites within several multimers. The analyses showed that a fraction of each of them is characterized by 4% divergence, while the amounts of dimer, tetramer, and octamer suggest that they have undergone 2-4 times more divergence than that. These results, coupled with the data on sequence variants that are more prevalent in the dimer, indicate that amplification of divergent repeating units could easily explain enhanced amounts of selected multimers. PMID- 6248868 TI - Recombination genes on the Escherichia coli sex factor specific for transposable elements. AB - The Escherichia coli sex factor stimulates precise excision of transposons Tn5 and Tn10 from sites either within the bacterial chromosome or within the factor itself. We have isolated two kinds of mutations that affect this activity. The ferA mutations eliminate the stimulation; the ferB mutations enhance it in the presence of FerA+. We conclude that ferA defines a sex factor gene that stimulates precise excision. The ferB mutations also specifically increase the rate of recombination between two IS3 elements on F' lac-pro (F'128) in a reaction that requires the product of recA. The stimulation of this recombination by ferB also requires an active ferA gene, which implies that the ferA gene stimulates this reaction as well as precise excision. A ferA mutation was mapped at 84.2 kilobases on the F factor, and a ferB mutation was mapped at 82.5 kilobases. The fer mutants were obtained by an approach that permits the isolation of mutants affecting precise excision. PMID- 6248869 TI - Mutations preventing transpositions of yeast mating type alleles. AB - Homothallic strains of Saccharomyces cerevisiae can switch from one mating type to the other as often as every cell division. The conversion of mating type alleles (from MATa to MATalpha or vice versa) depends on other, unexpressed copies of a or alpha information that can be transposed to MAT. Previously, "inconvertible" mutations within MATalpha and MATa have been described that block the excision of the MAT allele. In this paper we describe two cis-acting mutations that also impair mating type switching and lie very near, but outside, the MAT locus. Both "stuck" mutations, stk1 and stk2, diminish the efficiency of converting MATa to MATalpha to less than 10% of normal. The stk1 mutation also slightly reduces conversion of MATalpha to MATa, whereas stk2 has no discernible effect. Unlike the inconvertible MATalpha-inc and MATa-inc mutations within MAT, the stk mutations are not replaced by wild-type sequences after the "stuck" cells occasionally switch to the opposite mating type. Because these mutations are not "healed" by mating type conversions, they must lie in sequences outside of the transposable mating type information. These results indicate that the efficient replacement of MAT alleles depends on sequences both within and adjacent to the MAT locus. Among subclones of homothallic stk MATa strains, approximately 2% show "illegal" transpositions of mating type genes. In these colonies the silent copy of alpha information at the HMLalpha locus has been converted to a, without any change of MATa or the silent a copy at HMRa. Such conversions of the unexpressed library genes are not found in wild-type homothallic strains that can switch mating type efficiently, but they are found in MATa-inc and MATalpha-inc strains. It appears that all of the cis-acting mutations within or adjacent to mating type result in these unusual switches of mating type information at HML and HMR. PMID- 6248870 TI - Structure and organization of transposable mating type cassettes in Saccharomyces yeasts. AB - Cell type in Saccharomyces yeasts is regulated by two transposable blocks of DNA, the a and alpha cassettes. There are three loci where either cassette can exist. At the HML and HMR loci the cassettes are not expressed. The cassette at the MAT locus is expressed and controls the cell type. Changes of cell type involve transposition-substitution of cassettes from HML or HMR into MAT. We recently reported the molecular cloning of the alpha cassette at the HML locus, HML alpha, and showed that it contained sequences homologous to HMR and MAT. Using HML alpha as a hybridization probe, we have isolated HMLa, HMR alpha, HMRa, MAT alpha, and MATa. Heteroduplex analysis and restriction endonuclease mapping studies indicate that the a and alpha cassettes differ by a substitution corresponding to about 750 base pairs in alpha and about 600 base pairs in a. The HML, HMR, and MAT loci have regions of homology flanking the position of the a versus alpha substitution. We have used specific chromosome rearrangements fusing MAT and HML and MAT with HMR to orient the cloned sequences on the genetic map and have found that all three genes have the same left-to-right polarity on the chromosome. PMID- 6248871 TI - Cytoplasmic transfer of DNA containing simian virus 40 sequences into mouse 3T3 cells. AB - This paper describes the rare cytoplasmic transmission of defective simian virus 40 (SV40) viral DNA from enucleated cells (i.e., cytoplasts) of the SV40 transformed mouse cell line SVT2 (chloramphenicol-resistant) into cybrid cells formed by fusion of these cytoplasts with BALB/c 3T3 cells (thymidine kinase deficient). The cybrids were selected in medium containing 1% serum, bromodeoxyuridine, and chloramphenicol. They were identified by their 3T3 chromosome content, by the instability of tumor (T)-antigen expression, by their transformed phenotype, and by their drug resistance. The yield of rare cybrids was about 5 x 10(-7) 0.1% of the yield on medium with 10% serum. The presence of the SV40 genome was detected by the expression of SV40-specific T antigen and confirmed (unpublished data) by hybridization of viral DNA probes with restriction enzyme fragments of nuclear DNAs from cybrid clones. Restriction site mapping (unpublished data) showed that at least 1 kilobase of host flanking DNA on each side of the SV40 DNA was included in the transferred segment. The transforming DNA was not stably integrated initially, as judged by cellular heterogeneity in T-antigen expression. Stable T-antigen-positive and negative subclones were recovered in 10% serum; instability could be retained for at least 30 doublings during growth in 1% serum. The instability is interpreted as evidence of non-integration or unstable integration of the transferred DNA into the host genome. The cytoplasmic transfer is interpreted as evidence that chromosomal fragments or intact chromosomes can be transferred rarely through the cytoplasm in cybrid crosses. PMID- 6248872 TI - Prenatal diagnosis of sickle cell anemia by restriction and endonuclease analysis: HindIII polymorphisms in gamma-globin genes extend test applicability. AB - Polymorphism for a Hpa I restriction endonuclease site associated with about 60% of beta S genes in American Blacks allows exact prenatal diagnosis of sickle cell anemia by amniocentesis in 36% of couples at risk. In three families in whom exact diagnosis by Hpa I sites was impossible, we found analysis for the presence of polymorphic HindIII sites in the G gamma and A gamma intervening sequences would allow an exact prenatal diagnosis of sickle cell status in all three. In one of these families, the presence of an A gamma HindIII site in amniocyte DNA confirmed the diagnosis (sickle cell trait) made by synthetic studies using fetal erythrocytes obtained at fetoscopy. Studies of other Black families and individuals provide evidence for linkage disequilibrium in the G gamma-A gamma delta-beta gene complex involving the four sites, G gamma HindIII, A gamma HindIII, beta S, and Hpa I, which span 33 kilobases (kb). Ten of 14 chromosomes bearing a beta S gene in a 7.6-kb Hpa I fragment contained a G gamma but not an A gamma HindIII site, whereas 16 of 16 chromosomes bearing a beta S gene in a 13-kb Hpa I fragment lacked both the G gamma and A gamma HindIII sites. Two-thirds of beta A-bearing chromosomes lacked both G gamma and A gamma sites, whereas one third contained either the G gamma or both G gamma and A gamma sites. These data demonstrate that combined analysis of both Hpa I and HindIII polymorphisms and verification of their linkage phase should increase the fraction of couples for whom amniocentesis can provide an exact diagnosis of sickle cell status from 36% to greater than 80%. PMID- 6248873 TI - Specific receptors for the serum thymic factor (FTS) in lymphoblastoid cultured cell lines. AB - The interaction of the synthetic serum thymic factor (FTS, "facteur thymique serique") with human T lymphocytes from two established T cell lines (1301 and HSB2) was studied by using [3H]FTS. At 30 degrees C, in the presence of 10 nM labeled FTS, a steady state was observed within 120 min. Bound labeled FTS was dissociated by simultaneous addition of an excess of unlabeled FTS (dissociation constant Kd = 3 nM). The binding of [3H]FTS was reduced to 10-20% when unlabeled FTS was added at 20 microgram/ml (20 micro M), but not when unrelated peptides or FTS analogues differing from FTS by only one amino acid residue were added. No FTS binding was detectable on B and null cell lines or on two T cell lines other than 1301 and HSB2. These data indicate that only certain T cell subsets possess receptors with high affinity and specificity for FTS. PMID- 6248874 TI - Presence of allograft-rejection resistance in simian virus 40-transformed hamster cells and its possible role in tumor development. AB - LSH Syrian hamster cells transformed in vitro by simian virus 40, which is oncogenic for hamsters, are resistant to rejection by adult allogeneic CB hamsters. In contrast, simian virus 40-transformed cells from other species are usually not oncogenic in immunocompetent autologous or isologous hosts. The ability of simian virus 40 to convey resistance to an allograft-type host response to transformed hamster cells may be important in determining the tumor inducing capacity of these cells and could, in part, explain the species-specific oncogenicity of this virus. PMID- 6248875 TI - Persistence of increased platelet cyclic AMP induced by prostaglandin E1 after removal of the hormone. AB - Prostaglandin E1 (PGE1) covalently linked to omega-NH2-hexyl-agarose (PGE1-hexyl agarose) stimulates the activity of human platelet adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] 3-fold over control level at 60 sec when stirred at 1200 rpm at 37 degrees C. The time course exhibited a lag phase of 20 sec, a rapid increase to a maximum plateau between 60 and 80 sec, and a more gradual decrease to basal level at about 120 sec. During this entire period of incubation PGE1-hexyl-agarose could be easily separated; therefore it bound only transiently to the platelet. No prostaglandin(s) were found to be released into plasma. The stimulation of adenylate cyclase activity by the insolubilized hormone was dependent on the rate of collision as influenced by the speed of stirring. Removal of the insoluble PGE1 before the end of the lag period (10 sec) prevented the increase of adenylate cyclase. In contrast, separation of PGE1 hexyl-agarose from platelets by filtration after the lag period (at 30 or 40 sec) allowed the stimulation of the enzymatic activity to continue to completion in the absence of the hormone. The results suggest that PGE1 initiates molecular events leading to an increase of adenylate cyclase that do not require its continued presence for maintenance of the stimulated state. PMID- 6248876 TI - Monoclonal antibody against a 250,000-dalton glycoprotein of Epstein-Barr virus identifies a membrane antigen and a neutralizing antigen. AB - An antibody-secreting hybrid cell line was produced by fusion of mouse myeloma cells with splenocytes from mice immunized with virions of the B95-8 strain of Epstein-Barr Virus (EBV). The monoclonal IgG antibody was shown to have anti-EBV activity by the following criteria: (i) It reacted with the membranes and the cytoplasm of seven different EBV-producing lines, but with no nonproducing line. (ii) The individual cells identified by the murine antibody were shown to be the same cells identified by a human serum having anti-EBV activity. (iii) The antibody significantly reduced the infectivity of two independent strains of EBV (namely, P3HR1K and B95-8). The antigen being recognized was characterized by immunoprecipitations of radiolabeled EBV-producer cell lysates. A single glycoprotein with an estimated molecular weight of 250,000 was identified. It is concluded that neutralization of EBV can be achieved by an IgG-class monoclonal antibody directed against a single antigenic site on a 250,000-dalton glycoprotein, which is a constituent of the EBV virion. PMID- 6248877 TI - In vitro construction of a B-tropic virus by recombination: B-tropism is a cryptic phenotype of xenotropic murine retroviruses. AB - A B-tropic virus was isolated in vitro from the progeny of mouse cells doubly infected with N-tropic and xenotropic murine leukemia viruses. Biological and structural evidence is presented suggesting that the phenotypically silent structural marker for B-tropism, expressed by the xenotropic virus p30, was transferred to an N-ecotropic virus via recombination, thus resulting in the expression of a B-ecotropic murine leukemia virus. PMID- 6248878 TI - Synthesis and circularization of N- and B-tropic retroviral DNA Fv-1 permissive and restrictive mouse cells. AB - Production of various forms of nonintegrated viral DNA was measured in cultured mouse cells carrying different Fv-1 alleles early after infection with N-tropic or B-tropic retroviruses. Quantitative analyses were performed by agarose gel electrophoresis, transfer to diazobenzyloxymethyl-paper, and molecular hybridization. In permissive infection of Fv-1n cells (NIH Swiss and DBA mouse strains) with N-tropic virus and of Fv-1b cells (BALB/c and C57BL/6 strains) with B-tropic virus, form III (double-stranded linear) DNA first appeared at 3-4 hr and reached a maximum at 8-10 hr; two form I (closed circle) DNAs appeared at 7-8 hr and reached a maximum at or beyond 12 hr. In the two Fv-1b cells infected with N-tropic virus and in DBA (Fv-1n) cells infected with B-tropic virus, formation of the two form I DNAs was quantitatively restricted but formation of form III DNA was unaltered. In Fv-1n NIH Swiss mouse embryo cells infected with B-tropic virus, the level of form III DNA was markedly depressed and hence the two form I DNAs were not detectable. In C57BL/6 cells as well as in DBA/2 cells 12 hr after infection, the quantity of form III DNA varied directly with the amount of restricted virus, whereas the quantity of form I DNA varied according to the square of the amount of restricted virus. The significance of these results for understanding the molecular basis of retrovirus replication and its restriction by the Fv-1 gene is discussed. PMID- 6248879 TI - Epstein-Barr virus (B95-8) DNA VII: molecular cloning and detailed mapping. AB - Two of the Sal I fragments and all of the internal BamHI fragments (with the exception of BamHI c, a 0.6 x 10(6) dalton fragment) of Epstein-Barr virus (EBV) DNA have been cloned in pBR322. The termini and other parts of the DNA (including the EcoRI fragment which contains BamHI c) have been cloned as EcoRI fragments in bacteriophage Charon 4A. The cloned DNAs have been used to derive a complete map of the BamHI fragments of EBV DNA and to align the BamHI, EcoRI, HindIII, and SalI cleavage sites in EBV DNA. PMID- 6248880 TI - Identification of a proviral genome associated with avian myeloblastic leukemia. AB - We have identified and isolated a presumptive leukemogenic provirus from myeloblasts of a chicken in which leukemia had been induced by avian myeloblastosis virus (AMV). Leukemic myeloblasts isolated from peripheral blood or from converted yolk sac cultures of various strains of chickens, regardless of the endogenous proviral content or AMV pseudotype used for infection, contain an EcoRI 2.2-megadalton (MDaI) and a HindIII 2.6-MDal proviral fragment. A proviral genome flanked by chicken DNA sequences on either side and containing both the EcoRI 2.2-MDal and the HindIII 2.6-MDal fragments was inserted by molecular recombination into lambda phage Charon 4A and then cloned. This presumptive AMV proviral genome has a mass of approximately 4.9 MDal and contains terminal redundancies with respect to 3' viral RNA sequences. PMID- 6248881 TI - Characterization of the transforming gene of Fujinami sarcoma virus. AB - The src gene present in all avian sarcoma viruses is not present in the genome of Fujinami sarcoma virus, a potent sarcoma-inducing virus in chickens. Fujinami virus is defective and requires helper virus for replication. RNA from a mixture of helper and transforming viruses consists of two components, 35S and 28S. Oligonucleotide fingerprinting of each RNA component revealed that the 35S component was identical to the RNA of the helper virus. Thus, the genome of Fujinami virus must be the 28S RNA, which corresponds approximately to a molecular weight of 1.7 x 10(6) or 5300 nucleotides. Fujinami viral RNA shares several oligonucleotides with helper viral RNA at both 3' and 5' ends but contains a unique sequence of at least 3000 nucleotides in the middle of the genome. Fujinami viral RNA contains no src-specific oligonucleotides of the Rous sarcoma virus genome and did not hybridize with DNA complementary to the src sequences. The 60,000-dalton src protein of Rous sarcoma virus was undetectable in Fujinami virus-transformed cells. Instead, these transformed cells contain a protein of 140,000 daltons precipitable by antisera against virion proteins, which is likely to be the transforming protein of this virus. PMID- 6248882 TI - Recombinants between avian sarcoma virus genome and chicken helper factor gene of the host cell: cloning by transfection. AB - Chicken cells of chicken helper factor-positive (chf+) phenotype were infected with a cloned (envE-free) Rous sarcoma virus, subgroup D, and examined for the presence of parent and recombinant proviruses by transfection in chicken and turkey cells, respectively. It was found that most parent virus DNA is integrated into the host cell genome during the first 18 hr after infection, and no significant integration occurs between 18 and 72 hr after infection. On the other hand, no recombinant virus DNA was detected at 18 hr, although both unintegrated and integrated (provirus) forms of this DNA occurred 72 hr after infection. Recombination proviruses were also found in chronically virus-infected chf+ cells but not in chf- cells lacking virus-related RNA. Our results show that recombinants between the exogenous virus and endogenous chf gene can be cloned from the DNA of the host cell by transfection and suggest that a second replicative cycle of the virus is required to generate such recombinants. PMID- 6248883 TI - Memory neuron: synapse microchemistry for the memory component of a neuroconnective brain model. AB - This paper examines the synaptic microchemistry required if a memory neuron is to have the operating characteristics previously attributed to it [Wooldridge, D.E. (1980) Proc. Natl. Acad. Sci. USA, 77,2305-2308]. It is concluded that the requirements can be met by a combination of membrane mechanisms not very different from those that are commonly postulated to explain the properties of known types of neurons. PMID- 6248884 TI - Regulation of cyclic AMP formation in brain tissue by alpha-adrenergic receptors: requisite intermediacy of prostaglandins of the E series. AB - The accumulations of cyclic AMP elicited by norepinephrine in slices of rat cerebral cortex or hypothalamus were markedly reduced after incubations with prostaglandin synthetase (8,11,14-eicosatrienoate, hydrogen-donor:oxygen oxidoreductase, EC 1.14.99.1) inhibitors such as indomethacin, aspirin, flufenamic acid, and acetoaminophen. Responses of cyclic AMP-generating systems to beta-adrenergic agonists or adenosine were unchanged by treatment with indomethacin and the reduction in the norepinephrine response appeared due primarily to a loss of the alpha-adrenergic component. The accumulation of cyclic AMP elicited by prostaglandin E2 [mean effective dose (EC50) 4 micro M] was increased by 2-fold by treatment with indomethacin. The alpha-adrenergic component of the norepinephrine response was fully restored by very low concentrations of prostaglandin E2 (EC50 20 nM). Prostaglandins of the F series had no effect on cyclic AMP generation under a variety of conditions. It appears that low levels of prostaglandins of the E series are required--perhaps by a calcium-dependent mechanism--for the expression of alpha-adrenergic receptor mediated activation of cyclic AMP formation in brain tissue. PMID- 6248885 TI - Cluster formation of opiate (enkephalin) receptors in neuroblastoma cells: differences between agonists and antagonists and possible relationships to biological functions. AB - Neuroblastoma cells were used to study the surface distribution and organization of opiate (enkephalin) receptors and the possible relevance of changes in these variables to biological functions. Opiate receptors readily form clusters that are visible by image-intensifier fluorescent microscopy and are localized on both the cell body and processes. These clusters do not become internalized even during prolonged incubation periods. The receptors appear to pre-exist largely in a diffuse state, with only a very small number pre-existing as clusters. The clusters are induced within 1 hr and they are stable for prolonged (7-9 hr) periods, even after removal of the receptor-bound ligand. Agonists and antagonists are both equally capable of inducing receptor clustering. However, the clusters induced by agonists are different from those induced by antagonists; the former can be dispersed by treatment with dithiothreitol. This dispersion requires removal of the receptor-bound agonist, indicating that the hormone protects or stabilizes disulfide bonds which are critical for maintenance of the clustered state. Pretreatment of cells with sulfhydryl-blocking reagents (iodoacetate, iodoacetamide, and N-ethylmaleimide) prevents cluster formation but does not alter the ability of agonists to inhibit adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activity. Neither the number nor the affinity of binding sites is altered by pretreatment with opiates. These studies suggest that at least the acute, immediate biological effects of opiates and enkephalins occur prior to and are independent of the formation of gross receptor clusters. The possible relationship of cluster formation to the actions of opiates remains to be determined. PMID- 6248886 TI - Ouabain-resistant hyperpolarization induced by insulin in aggregates of embryonic heart cells. AB - Spheroidal aggregates formed from trypsin-dissociated 14-day embryonic chicken hearts after 48 hr of rotation on a gyratory shaker. Intracellularly recorded resting membrane potentials of aggregates bathed in 1.3 mM K+ balanced salt solution had a mean (+/- SD) of 64 +/- 4 mV. After a stable potential was achieved, addition of 1-100 nM sodium bovine insulin caused a slow hyperpolarization of up to 19 mV after 4-5 min, followed, in some cases, by a further, more rapid, shift to a potential near EK. Equivalent hyperpolarizations were observed when insulin was added in the presence of 10 mM ouabain, indicating that enhanced Na+,K+ pump activity was not responsible for the change in membrane potential. The concentration of insulin that produced half-maximal hyperpolarization (2 nM) corresponded to the association constant of a high affinity insulin receptor, suggesting that binding to this class of receptors led to the change in membrane potential. Steady-state current-voltage curves from current clamp experiments suggested that insulin produced an increase in slope conductance at potentials near rest by inducing an outward current with an apparent potential negative to -90 mV. PMID- 6248887 TI - Independence of the positive inotropic effect of ouabain from the inhibition of the heart Na+/K+ pump. AB - Isolated left atria from guinea pigs were stimulated at 3.3 Hz and bathed at 30 degrees C in Tyrode's solution containing 6 mM KCl. After equilibration, this solution was replaced by a low-K solution or by Tyrode's solution containing ouabain or dihydroouabain. These treatments evoked an increase in the contractility of the atria. The time to peak increase was about 30 min, and the inotropic effect was sustained for at least 40 min. After 30 min, 42K was added to the bathing solution in order to estimate the activity of the Na+/K+ pump. A linear relationship was observed between the degree of inhibition of the Na+/K+ pump and the increase in systolic tension. The regression line was the same for low-K solutions and dihydroouabain but not for ouabain. For a given degree of inhibition of the pump, ouabain evoked a higher increase in contractility. These findings indicate that inhibition of the Na+/K+ pump can be the only mechanism responsible for the positive inotropic effect of dihydroouabain but cannot be the sole mechanism for that of ouabain. PMID- 6248888 TI - Propagation of mammalian cells and of virus in a self-regulating fermentor. PMID- 6248890 TI - Adaptation of membrane-associated determinants is an outgrowth of their metabolism. AB - The quantity of receptors expressed by specialized cells for hormones, foreign antigenic substances, and other chemical stimuli diminishes after they associate with ligands, correlating with a specific reduction in the responsiveness of the cell to further stimulation. Ligand-induced adaptation of membrane receptors may be akin to antigenic modulation--the reversible disappearance of membrane associated determinants stimulated by specific antibodies. Antigenic modulation has been studied extensively in the thymus-leukemia (TL) system of mouse leukemias. Antibody-induced changes in the quantities of TL antigens expressed by ASL-1 and RADA-1 cells, independently arising leukemia cell lines of strain A mice, are outgrowths of their metabolic turnover. After interacting with TL antibodies, the rate of TL antigen disappearance from the membrane increases while the rate of antigen synthesis remains unchanged. Antiserum with specificities for two membrane-associated determinants of ASL-1 cells, TL and a tumor-associated antigen, leads to modulation of TL antigens alone; the tumor antigen persists. Selectivity of modulation is taken as an indication that complex cellular controls govern the affect of antiserum on the expression of membrane antigens. To detect the presence of regulatory controls governing the expression of membrane determinants, stable somatic hybrids of ASL-1 murine leukemia cells and LM(TK)- cells, a sustained mouse cell line, were prepared and antiserum affects on membrane antigen expression were investigated. The metabolic half-lives of each of three antigen determinants investigated was distinct from the others examined. The hybrid cells have lost their capacity to mudulate TL antigens. TL antigens of hybrid cells, unlike those of parental ASL-1 cells, continue to be expressed in the presence of high titers of TL antiserum. Similarities between antigenic modulation and down regulation exist, among which are the fate of receptor-ligand complexes, changes in their metabolism after binding to ligand, and the dependence of the reactions upon continued sources of cellular energy. PMID- 6248889 TI - Regulation of beta-adrenergic receptor density in the control of adrenergic responsiveness. PMID- 6248891 TI - Molecular identification and properties of two cell surface receptors playing roles in mitogenesis and epigenesis. AB - Studies leading to the identification of cell surface receptor macromolecules which specifically recognize a hormone, epidermal growth factor (EGF), or gp70, the coat antigen of the C-type RNA tumor viruses, have been described. EGF receptors are internalized and processed by lysosomal protease action after interaction of receptor and EGF. Other hormones, which resemble EGF in their ability to trigger mitogenesis in cultured cells, interact with the EGF receptor in a yet to be defined, but probably indirect way, decreasing the number of EGF binding sites on the cell surface. The evidence at this point indicates that these hormones interact with EGF receptors through the communal utilization of a shared cellular mechanism for internalization of their receptors and the EGF receptors. The receptor for gp70 is not internalized in response to gp70 binding, but is instead shed into the medium by cultured cells. This receptor protein BPgp70 has now been isolated and purified to apparent homogeneity. Antibodies to BPgp70 completely block gp70 binding to cells at low concentration, indicating that BPgp70 is the physiological receptor for gp70. PMID- 6248892 TI - Diagnosis of fetal lung maturity. PMID- 6248893 TI - Membrane Na+K+ATPase activity: changes using an experimental model of alcohol dependence and withdrawal. AB - An alcohol dependent states was induced in rats via gastric intubation. Alcohol was given three times daily for seven days in increasing doses, the final dose and concentration varying from rat to rat, being adjusted according to weight loss and state of intoxication. After seven days dosing, alcohol was withdrawn and twenty hours later an audiogenic stimulus was given to induce convulsions. Na+K+ATPase activity was measured in the hippocampus of rats during alcohol administration and during withdrawal. Animals which received twenty-one doses of alcohol showed a significant increase in Na+K+ATPase activity compared with controls. On withdrawal of alcohol, the enzyme activity fell, but remained higher than control values. In the withdrawal groups, membrane Na+K+ATPase levels were increased significantly compared to control levels in the order: no convulsion less than with convulsion less than postconvulsion. It is concluded that Na+K+ATPase activity is modified during chronic alcohol administration and during seizures induced after alcohol withdrawal by audiogenic stimulation. PMID- 6248894 TI - Lysine vasopressin attenuation of diethyldithiocarbamate-induced amnesia. AB - The effect of lysine vasopressin on diethyldithiocarbamate-induced amnesia for a step-through passive avoidance task was studied in rats. It was determined that although the hormone attenuates the amnesia when it is administered prior to retrieval testing, it fails to do so when it is injected prior to training. These results are consistent with the reports of others which demonstrate the reversal of diethyldithiocarbamate-induced amnesia by catecholamine agonists. PMID- 6248895 TI - The failure of alpha-methyl-para-tyrosine to produce supersensitivity in 6-OHDA lesioned rats. PMID- 6248896 TI - beta-Adrenergic manipulation in amygdala central n. alters rabbit heart rate conditioning. AB - The present study was conducted to assess the effects of beta-adrenergic manipulation within the central nucleus of the amygdala on Pavlovian heart rate conditioning in the rabbit. Administration of the beta-adrenergic antagonist dl propranolol into the central nucleus impaired the acquisition of conditioned heart rate responding compared to a vehicle injected control group. No significant effects of dl-propranolol on either baseline heart rate or on the heart rate orienting response were observed. The effect of dl-propranolol on conditioning exhibited stereospecificity, and animals receiving combined intracerebral injections of dl-propranolol and the beta-adrenergic agonist 1 isoproterenol did not exhibit comparable conditioning impairments. In addition, dl-propranolol administration dorsal to the central nucleus or into amygdala sites anterior or posterior to the central nucleus was less effective. These results support the interpretation that beta-adrenergic activity within the central nucleus region of the amygdala complex contributes to the acquisition of classically conditioned heart rate responding. PMID- 6248897 TI - Effects of delta 9-THC on human platelet phospholipids. AB - The possible change in Platelet lipids after smoking delta 9-THC was studied in chronic hashish users. The fluctuations of total phospholipid content is related to alterations of individual phospholipids. Changes in phosphatidylcholine, phosphatidylinositol and phosphatidylethanolamine are discussed in relation to membrane derangement leading to the increased rate of platelet lysis and aggregation under high doses of the drug. PMID- 6248898 TI - Intraventricular ACTH reduces social interaction in male rats. AB - Intraventricular ACTH (1.25 microgram), ACTH (1.6 microgram) and ACTH:D-Phe (1.6 microgram) resulted in significant reductions in the time that pairs of male rats spent in active social interaction. This decrease in social behaviour was not accompanied by a decrease in motor activity. The results are similar to those previously found with peripheral administration of ACTH and suggest that these behavioural effects of ACTH are centrally mediated. None of the ACTH fragments had a significant effect on the latency with which thirsty rats started drinking in an unfamiliar environment. The results are discussed in relation to a possible anxiogenic action of ACTH. PMID- 6248899 TI - Pain modulating and reward systems: a single brain mechanism? PMID- 6248901 TI - Effect of various antiinflammatory drugs on plasma ACTH and cortisol levels in rats. PMID- 6248900 TI - Some features of modern pharmacology. PMID- 6248902 TI - beta-Adrenergic sensitive adenylate cyclase in rat posterior pituitary. PMID- 6248904 TI - Tranylcypromine stereoisomers, monoaminergic neurotransmission and behavior. A minireview. AB - Studies on the effects of the d- and l-stereoisomers of tranylcypromine on locomotor activity, aggressive behavior, hindlimb reflexes, head twitches and behaviors produced by reserpine in rats are reviewed. The d-isomer is found to produce stereotypic behavior and head twitches, to enhance extensor hindlimb reflexes, and to alter effects of reserpine on locomotor activity. The l-isomer is shown to enhance vertical and horizontal locomotor activity and to cause aggressive behavior, but failed to influence hindlimb reflexes, effects of reserpine, or to produce head twitches. Biochemical and pharmacological studies suggest that the d-isomer influences mainly tryptaminergic neurotransmission while the l-isomer affects primarily catecholaminergic neurotransmission. It is concluded that tranylcypromine stereoisomers have stereoselective effects on behavior and monoaminergic neurotransmission. The implications of the findings for the notion that the antidepressant effects of tranylcypromine are due to inhibition of MAO are briefly discussed. PMID- 6248905 TI - The molecular aspects of visual photoreceptors. PMID- 6248903 TI - Acetylcholine-releasing effect of primycin, a highly active antibiotic. AB - The effect of primycin, an antibiotic known to inhibit potassium conductance, was studied on acetylcholine (ACh) release from the nerve terminals of the Auerbach plexus and cortical slice of the rat. Primycin enhanced the resting release of ACh; however, it failed to affect the amount of ACh released by a single shock. It has no effect on Na+K+-activated ATPase. Its effect on Ach release was prevented by tetrodotoxin and by Ca removal. It is concluded that its effect on potassium conductance might account for its ACh-releasing effect: it produces depolarization and spontaneous firing. PMID- 6248906 TI - Sodium transport across toad urinary bladder: a model "tight" epithelium. PMID- 6248907 TI - Immunology of acetylcholine receptors in relation to myasthenia gravis. PMID- 6248908 TI - Transport of protons across membranes by weak acids. PMID- 6248910 TI - Investigations into the nature of the dexamethasone and ACTH effects upon learned taste aversion. PMID- 6248909 TI - Sodium and potassium ion pump in kidney tubules. PMID- 6248911 TI - Amygdalectomy induced deficits in conditioned taste aversion: possible pituitary adrenal involvement. PMID- 6248912 TI - Effects of ACTH4--10 on self-stimulation behavior in the rat. PMID- 6248913 TI - Dihomogammalinolenic acid (20:3 omega 6) is more anti-aggregatory than eicosapentaenoic (20:5 omega 3) in a platelet-endothelial cell mixture. AB - The effect of 20:3 omega 6, the precursor of 1 series prostaglandins was to inhibit platelet aggregation more strongly than either 20:5 omega 3, the precursor of 3 series prostaglandins or 20:3 omega 3 which is not a substrate of prostaglandin synthetase. When platelets and dissociated endothelial cells were pretreated with 20:3 omega 6, platelet aggregation in the presence of endothelial cells was much more inhibited than after 20:5 omega 3 pretreatment. PMID- 6248914 TI - The ovulation blocking effect of cannabinoids: structure-activity relationships. PMID- 6248915 TI - Adrenal steroid interactions in female sexual behavior : a review. PMID- 6248916 TI - Withdrawal-like behaviour induced by inhibitors of biogenic amine reuptake in rats treated chronically with delta 9-tetrahydrocannabinol. AB - The effects of the biogenic amine reuptake inhibitors fluoxetine, clomipramine and imipramine on the behaviour of rats after chronic treatment with delta 9 tetrahydrocannabinol (delta 9-THC) for 5 and 10 days were examined. Rats with permanently in-dwelling IV cannulae were injected twice daily with doses of delta 9-THC (2-6 mg/kg). delta 9-THC treatment reduced the rate of body weight gain and induced the typical biphasic modifications of behaviour. Tolerance developed to both of these effects. On days 6 and 11 of the experiment, rats were injected IP with 15 mg/kg imipramine HCl, clomipramine HCl or fluoxetine HCl, and behaviour, consisting of writhes, backward kicks, jumps and wet shakes, was observed for the next 30 min. Each of the amine reuptake inhibitors induced changes in behaviour, the severity of which appeared to correlate with their ability to inhibit the reuptake of 5-hydroxytryptamine (5-HT). It is suggested that tryptaminergic mechanisms are involved in the production of a withdrawal-like behaviour after chronic delta 9-THC treatment. PMID- 6248917 TI - Effect of beta-endorphin and naloxone on acquisition, memory, and retrieval of shuttle avoidance and habituation learning in rats. AB - Naloxone impairs acquisition of shuttle avoidance behavior (0.8 mg/kg IP) and habituation to a rearing response to a tone (1.6 mg/kg IP) in rats. beta Endorphin (2 microgram/kg IP) has no effect on acquisition, but, when given prior to test sessions, facilitates retrieval of the two tasks. Naloxone has no effect of its own upon retrieval. In addition to these effects, the pretraining administration of beta-endorphin disrupts, and that of naloxone facilitates retention of the two tasks. The results are consistent with the hypothesis that these two forms of learning are state-dependent on the release of beta-endorphin (and, perhaps, of other opiate peptides as well), that this substance is released during training in a sufficient amount for this purpose, and that, in addition, there is a physiological amnesic mechanism mediated by opiate peptides. Furthermore, the results are also consistent with previous observations that beta endorphin is released from the rat brain during training, but not during test sessions of the two tasks (Izquierdo et al., 1980b). The possibility is discussed that state-dependency and the amnesic effect comprise one single, rather than two separate mechanisms. PMID- 6248918 TI - The effects of beta-adrenergic stimulation and beta-adrenergic blockade on emotional reactions. PMID- 6248919 TI - [Aftercare in schizophrenic patients (author's transl)]. PMID- 6248920 TI - Reduction in cyclic nucleotide levels in the brain after a high dose of ionizing radiation. PMID- 6248921 TI - [Pathologic-anatomic reflections on portal hypertension (author's transl)]. AB - Portal hypertension is defined as an increase of the portal venous pressure over 20 cm H2O or 7 mm Hg, respectively. It may be induced by different types of portal venous stenosis or obstruction, primarily by cirrhosis and fibrosis of the liver and, less frequent by posthepatic disorders such as the Budd-Chiari syndrome or congestive heart failure. Portal hypertension is followed by ectasia and phlebosclerosis of the portal vein, by splenomegaly, ascites and by various types of collateral circulation. Among these, oesophageal varices, are most important since they often lead to acute upper gastrointestinal haemorrhage, the major complication of portal hypertension. Bleeding from oesophaeal varices is essentially based on atrophy of the squamous epithelium, caused by ischemia from local hypoxia and venous stasis. Portal hypertension and the frequently compromised blood clotting mechanism due to reduced synthesis of clotting factors in the liver aggravate the bleeding. Atrophy of the esophageal mucosa presents an area of decreased resistance likely to ulcerate with easy erosion of the varices- usually lying very superficially--; with mechanical irritation by food or peptic erosion from gastroesophageal reflux being frequent inducers of hemorrhage. PMID- 6248922 TI - [Radiology disease of rare liver tumors (author's transl)]. AB - The past decade has shown an increase in the number of rare primary hepatic tumors, such as focal nodular hyperplasia (FNH), and hepatocellular adenoma and carcinoma. Some examples serve to demonstrate the value of scintigraphy, ultrasound, angiography and CT in the diagnosis of these lesions. Furthermore, the value of the radiographic finding for treatment and follow-up studies is pointed out--in conservative as well as surgical treatment. PMID- 6248923 TI - [Klippel-Trenaunay-Weber syndrome]. PMID- 6248924 TI - [Primary nodular lymphoma of the left pararectal space]. PMID- 6248925 TI - [Malignant fibrohistiocytoma associated with multiple myeloma]. PMID- 6248926 TI - [Clinical and analytical implications in hepatomas]. PMID- 6248927 TI - [Morphology of primary hepatic carcinoma]. PMID- 6248928 TI - Mitochondrial heterogeneity in Aspergillus nidulans: evidence of in vivo transformation among different mitochondrial populations. AB - The distribution of mitochondria from Aspergillus nidulans on a dextran-sucrose gradient resulted in the fractionation of three bands. The lightest band presented the highest respiratory and cytochrome c oxidase activities and was also the most active in the incorporation of tritiated glycerol. Pulse-chase experiments with 3H-glycerol suggested that mitochondria from the light band was transformed to denser organelles as the organism grew. PMID- 6248929 TI - Effect of LH-RH and hypothalamic extracts on 3'-5'-cyclic-AMP pituitary levels of immature and adult female rats in vivo. AB - Adult female rat hypothalamic extract and LH-RH increased the 3'-5'-cyclic-AMP (cAMP) level of immature pituitary in vivo, while immature female rat hypothalamic extract had the opposite effect. LH-RH and immature female rat hypothalamic extract did not change the cAMP pituitary levels 60 min after injection to adult female rats. PMID- 6248930 TI - Patent and latent activities of cardiac membrane vesicles: distinctions between proteins of sarcolemma and sarcoplasmic reticulum. PMID- 6248931 TI - Energy metabolism and ion fluxes across cardiac membranes. AB - The possible role of the intracellular creatine kinase system in energy transport and in the metabolic control of ion fluxes across the cardiac cell membranes has been studied. The experimental data reported indicate that creatine kinases bound to the sarcolemmal membrane and to the membrane of sarcoplasmic reticulum are coupled to Na+, K+-ATPase and Ca2+-ATPase, respectively, and ensure rapid rephosphorylation of ADP produced in the ATPase reactions, maintaining a high and constant ATP:ADP ratio near the active centers of ATPases. The ability of creatine phosphate to increase the rate of activator calcium entry across the surface membrane into cardiac cells has been experimentally demonstrated. It is concluded that the intracellular creatine kinase system can exert metabolic control of heart muscle contraction. PMID- 6248932 TI - Role of phospholamban (22,000-dalton protein) in cyclic AMP-mediated control of Ca2+-dependent ATPase of cardiac sarcoplasmic reticulum. PMID- 6248933 TI - Calcium efflux from cardiac sarcoplasmic reticulum vesicles. PMID- 6248934 TI - Myocardial transmembrane potentials and adrenergic receptors. AB - The role of adrenergic amines in the genesis of cardiac arrhythmias is well known. Electrophysiological techniques of recording intracellular potentials have led to a better understanding of the cellular mechanisms by which these amines may induce arrhythmias. Stimulation of beta 1-adrenoreceptors increases automaticity, shortens action potential duration (APD), and may enhance slow action potential (AP) formation in depolarized Purkinje fibers (PF). Excitation of alpha-adrenoreceptors prolongs repolarization and plateau phase in PF. On the basis of the spectrum of antiarrhythmic activity in vivo and qualitatively different transmembrane effects on the canine PF, beta-adrenoreceptor blocking drugs can be subdivided into two distinct categories. Recent evidence with two new highly selective beta blockers, PS-6 and mepindolol, also suggests that at least two subgroups of cardiac beta 1-adrenoreceptors can be differentiated: beta 1i for inotropic and beta 1c for chrontropic actions of catecholamines. The effects of PS-6 in 5 x 10(-5) M concentration on isolated rabbit atria showed that this agent atangonized ouabain-induced arrhythmias and contracture. PS-6 (8 x 10(-6) M or more) reduced AP amplitude, phase 0 depolarization, APD, and phase 2 plateau phase in paced canine PF. These data suggest that PS-6 exerts a direct transmembrane effect on the canine PF. PMID- 6248935 TI - Cardiac histamine receptors. AB - Histamine can produce inotropic and chronotropic responses in both guinea pig and rabbit heart. In the guinea pig the responses are mediated primarily through stimulation of H2 receptors with H1 receptors being found mainly in left atria. In the rabbit H1 receptors predominate; H2 receptors are found only in right atria and are partially responsible for the chronotropic effect. H2 receptors are always associated with cyclic AMP, whereas H1 receptors are not. H2-histamine receptors and beta-adrenergic receptors have a number of properties in common. Stimulation of either receptor results in positive inotropic and chronotropic effects and increases in cyclic AMP and phosphorylase a. H2 and beta-adrenergic agonists will also both restore the action potential in K+-depolarized cardiac muscle. H1 and alpha-agonists, on the other hand, will also produce an inotropic effect. The effect is not dependent on cyclic AMP and can only be demonstrated under certain conditions. Neither agonist will restore the action potential in depolarized cardiac tissue. It is concluded that, although H2 and beta-agonists and H1 and alpha-agonists may have a common mechanism of action, the two groups of drugs (H2, beta versus H1, alpha) differ from each other with regard to mechanism. PMID- 6248936 TI - Membrane properties of aggregate of collagenase-dissociated rat heart cells. AB - Aggregates of collagenase-dissociated neonatal rat heart cells have been tested for several membrane properties and shown to be comparable with cells from the intact heart. Action potentials, recorded from driven aggregates, are fully suppressed by tetrodotoxin (TTX). Under Mn2+, the plateau phase of the action potential disappears and no more mechanical activity can be detected. In aggregates, therefore, apparently both the fast sodium inward current and a slow inward current, which is at least partly carried by Ca2+ ions, contribute to the action potential. Pacemaker activity in spontaneously active aggregates is enhanced by adrenaline and slowed down by acetylcholine. Adrenaline also increases the plateau phase amplitude of the action potential and thereby the rate of repolarization. Acetylcholine shortens the action potential duration and increases the resting membrane potential. The electrical coupling between the cells in the aggregates is so tight that the aggregate seems to behave passively, like a single cell. It is concluded that aggregates of collagenase-dissociated neonatal rat heart cells may be used to study active electrical properties using the voltage clamp technique. PMID- 6248937 TI - Cardiac metabolism: cetecholamines, calcium, cyclic AMP, and substrates. PMID- 6248938 TI - Purification and properties of phosphoprotein phosphatase from rabbit heart. AB - A low molecular weight phosphoprotein phosphatase acting on muscle phosphorylase a has been purified to homogeneity from rabbit heart by acid precipitation, ethanol treatment, and chromatography on Sephadex G-75 and Sepharose-histone. The purified enzyme showed a single band when examined by sodium dodecyl sulfate polyacrylamide gel electrophoresis; the molecular weight calculated by this method was 34,000. The S20,w value and Stockes radius for the enzyme were 3.45 and 24.0 A, respectively. Using these two values, a molecular weight of 35,000 was calculated. Purified enzyme showed a wide substrate specificity and catalyzed the dephosphorylation of phosphorylase a, glycogen synthase D, phosphorylated histone, and phosphorylated casein. A heat-stable protein inhibitor for this enzyme with phosphorylase a as the substrate was also shown to be present in crude extracts of rabbit heart. It inhibited the dephosphorylation of phosphorylase a by phosphoprotein phosphatase by decreasing the Vmax of the reaction. PMID- 6248939 TI - Inhibition cAMP-phosphodiesterase in the rat heart by pentoxifylline--a new xanthine derivative. AB - Pentoxifylline, a new xanthine derivative with properties favorably affecting the rheological profile of blood, was administered to male rats weighing 200--300 g in doses of 5, 10, 15, and 20 mg/kg of body weight for five days. Up to 27% of the intracellular cAMP-phosphodiesterase (cAMP-PDE) of the myocardium was dose dependently inhibited. A significant increase in the protein content of the heart (wet weight) was also recorded, but was unrelated to the dose of pentoxifylline and without evidence of cardiac hypertrophy. PMID- 6248940 TI - Cyclic AMP as mediator of catecholamine-induced enzyme release from isolated perfused working rat heart. AB - Adrenaline causes a dose-related increase in enzyme (lactate dehydrogenase) release from the isolated perfused working rat heart and a rise in tissue cAMP. Rates of both enzyme release and tissue cAMP fell with beta blockade by propranolol (plus pacing to maintain heart rate). Theophylline also increased enzyme release and tissue cAMP. Dibutyryl cAMP, but not butyric acid or external cAMP, increased enzyme release. Hence the release of enzyme is mediated by cAMP according to the criteria of Sutherland et al (11) for mediating the action of catecholamines. However, factors other than cAMP are operative because the extent of enzyme release and the tissue cAMP can be dissociated by variations in external calcium or magnesium or glucose, which modulate the effects of a given level of cAMP. PMID- 6248941 TI - Influence of cations and agents on sarcolemmal calcium binding. AB - Calcium binding to fragmented sarcolemma isolated from dog heart was measured by an ultracentrifugation technique. Two classes of binding sites with dissociation constants of 4.2 x 10(-5) M and 1.2 x 10(-3) M were identified. The maximum number of high and low affinity sites were 15 and 452 nmol/mg, respectively. The effects of various cations and drugs on calcium binding were studied in the presence of 0.1 mM total calcium. All cations tested inhibited calcium binding to a certain degree. La3+ (1 mM) and Mn2+ (1 mM) abolished calcium binding to the sarcolemma. The other divalent cation, Mg2+, used at a concentration of 1 mM, produced a partial inhibition Na+ and K+ also depressed calcium binding, with Na+ being the more potent inhibitor. Verapamil produced a depression at concentrations as low as 10(-7) M and abolished calcium binding at 10(-3) M. The effects of these cations and drugs on fragmented sarcolemma appear different from those reported for the isolated sarcoplasmic reticulum. Thus it is unlikely that the calcium binding observed was caused by a contamination of the sarcolemmal preparation by the fragmented sarcoplasmic reticulum. In addition, the calcium binding seems to be on the sarcolemma itself, rather than to the remaining fragments of the basement membrane, because the calcium binding was not significantly modified by pretreatment with purified neuraminidase (0.25 U/g of sarcolemma). PMID- 6248942 TI - Species-related difference in the heart sarcolemmal enzyme activities. AB - The sarcolemmal membranes were isolated by the hypotonic shock-LiBr treatment method from rat, guinea pig, rabbit, and dog hearts and their various biochemical activities were measured. The Mg2+-ATPase, Ca2+-ATPase, and 5'-nucleotidase were most active in rat heart homogenates as well as sarcolemmal membranes, whereas the adenylate cyclase and Na+, K+-ATPase were most active in guinea pig heart preparations. ATP-independent calcium binding activity of rat heart sarcolemma was the same as that of guinea pig heart membrane, whereas ATP-dependent calcium binding of rat heart preparation was negligible. Treatment of sarcolemma with 0.6 M KCl increased the adenylate cyclase and Na+, K+-ATPase activity in rat heart, but these activities were unaltered or decreased in other species. The gel electrophoretic pattern of protein bands and phospholipid composition of rat heart sarcolemma were different from those of guinea pig heart. Sarcolemma isolated from hearts by sucrose gradient method also showed species-dependent difference in the membrane-bound enzyme activities. These results have been interpreted to suggest species-related difference in calcium movements across sarcolemma and this may contribute to determining species-dependent difference in the regulation of myocardial calcium metabolism. PMID- 6248943 TI - Sarcolemmal calcium transport and drug action. AB - Sarcolemmal-rich microsomal fractions were isolated from rabbit ventricular muscle differential centrifugation and discontinuous sucrose gradient techniques. The fractions were characterized in terms of calcium binding, enzymatic activity, gel electrophoresis, and ultrastructure. Calcium binding and the initial rates of binding were assayed using 45Ca2+ and Millipore filtration in a reaction mixture containing 100 mM KCl, 5 mM MgCl2, 50 mM Tris, Ca2+, and either nitrilotriacetic acid (NTA) or adenosine triphosphate (ATP). The free calcium concentrations of the media were calculated using an ion complexes-in-solutions computer program with either an NTA or an ATP calcium buffering system. The Ca2+-accumulating activity of these sarcolemmal preparations involved more than one type of binding site. One type of site appeared to be rapidly saturable; calcium accumulation at these sites was energy independent. The second type of site required ATP for binding. Calcium accumulation at both sites was temperature and pH sensitive. These results are discussed in terms of the interaction of inotropically active drugs with the different types of binding sites. PMID- 6248944 TI - Respiratory effects of dopamine-induced inhibition of chemosensory inflow. AB - In pentobarbitone-anesthetized cats, intracarotid injections of dopamin (DA) 0.05 -20 micrograms produced transient ventilatory depression, enhanced by section of the contralateral carotid nerve and abolished by section of the ipsilateral one. I.v. injections of DA 0.02--2 micrograms-kg-1 also induced transient hypoventilation; this effect was abolished by bilateral section of the carotid nerves. Slow i.v. infusion of DA 10 micrograms-kg-1-min-1 elicited initially a pronounced hypoventilation followed by a steady-state of mild ventilatory depression; these changes were absent after bilateral carotid neurotomy. Recordings from carotid nerves showed that DA-induced decreases of chemosensory activity to 50% of its control did not modify ventilation, while chemosensory arrests transiently depressed ventilation to 40--75% of its control level. Interactions between the ventilatory and chemosensory depressant effects of hypertoxia and DA administration were also studied. It is proposed that the reflex decrease in ventilation caused by DA injections provides a measure of the tonic chemosensory drive exerted upon the respiratory center. PMID- 6248945 TI - [Interdisciplinary colloquium, January 20, 1978 Session, L. Ruyters, President. Diverticulosis of the colon. Etiology and pathogenesis of diverticulosis]. PMID- 6248946 TI - [Persistence of herpetic inflammation of the central nervous system four years after an episode of acute encephalitis (author's transl)]. AB - A patient was followed up for four years after an acute episode of encephalitis attributed to herpes because of the clinical and EEG features, the high serum antiherpetic antibody titers, the temporofrontal site of the lesions as shown by CT Scan. The clinical sequelae were non evolutive and the serum antiherpetic antibody titers remained at the same level (1/128) from the 10th day on. The CSF showed continuing pleiocytosis and slight elevation of protein with an increased proportion of IgG; moreover, four years later, the CSF antiherpetic antibody titers were elevated (1/16). These findings suggest that local production of antibody within the CNS may persist after acute herpetic infection. PMID- 6248947 TI - [Pulmonary biopsy]. PMID- 6248948 TI - [Possibilities of evaluation of the risk of tubercular infection in children and adolescents]. AB - Two indicators are of primary importance in the assessing the tuberculous endemia in a determined area: the prevalence of bacilliferic sources, especially of those that have been confirmed by bacteriological examinations (bacterioscopy), and the annual incidence of the tuberculous infection (the real infection risk). Possibilities are described, and examples provided, for approximation of the incidence of the tuberculous infection through: a) conversion index; b) the ratio between the prevalence of the tuberculous infection and the median tested age; c) the Styble-Meijer-Sutherland logarithmic ecuation; d) the nomogram variant with tables B and C established by Styblo-Meijer-Sutherland; e) the R. Narain graphic methods. For those countries in which BCG vaccination is practiced on an extensive scale the authors suggest the incidence risk indice could also be calculated, for supra-infection, which can be correlated and completed by the incidence (risk) of infection. PMID- 6248949 TI - [Investigation concerning some organizational aspects of the care of chronic bronchitis patients]. AB - The epidemiologic importance of chronic bronchitis is stressed, which justifies the preoccupation of the authors for finding the means of detection and diagnosis in view of the application of adequate therapeutical measures. An inquiry was used, taking the form of questionnaire concerning the various medical and social organizatory problems raised by chronic bronchitis. The questionnaire was sent for completion by the various sanitary directions in the districts. The answers were statistically processed and the results justify the necessity for a standardization of methods used in the detection and the diagnosis of patients with chronic bronchitis, as well as for other measures concerning these subjects. PMID- 6248950 TI - [Informational system in prevention and integrated fight against tuberculosis]. AB - The authors have sent out a special form to a total of 50 specialists and general practitioners, and their answers it appeared that these physicians consider necessary to review and to render more technical the system used for the information in view of the prevention and the integrated fight against tuberculosis. The authors recall the fundamental technical notions in this connection and present the generators and the recipients of information related to the fight against tuberculosis, the informational flow in the anti-tuberculous activity, the standardized informational instruments of the Ministry of Health and the informational channels which are accessible in the practice. In conclusion the authors present the stocking and the transfer of anti-tuberculous information, synthesized on a functional representation of the informational system in the prevention and the integrated fight against tuberculosis. PMID- 6248951 TI - [Considerations on the differentiated integration of bacteriological examinations for M. tuberculosis in some health units of the city of Jassy]. AB - The authors make an analysis of the modalities for the integration of the bacteriological examinations for M. tuberculosis in 3 sanitary units in the city of Jassy. In view of detecting pulmonary tuberculosis, although an improvement was noted in the activity of integration, an intensification is necessary of the culture examination in the present stage of the tuberculous endemia. Also a more close cooperation is necessary between laboratories from sanitary units, and with the central laboratory for cultures of M. tuberculosis. With regard to extra respiratory tuberculosis the large number of demands for bacteriological examinations from the hospital as well as from the ambulatory units, makes necessary the organization of diagnostic centres by specialities. PMID- 6248952 TI - [Clinical trial of amoxycillin in chronic bronchitis and bronchial dilatations]. AB - The therapeutic results were followed of amoxycilline after application in 57 cases of chronic bronchitis and bronchial dilatations that had been treated previously with antibiotics (including ampicillin--in 37 cases). The amount of amoxycilline was of 2 g per day, given in four 0,5 g doses. A total of 23,3 percent "very good" results were obtained (expectoration either disappeared completely or was reduced to 2--3 ml per day), and 40,4 percent "good" results (with expectoration down to less than one half of the initial amount). Thus in two-thirds of the cases the results were favourable. The cases that did not respond to ampicilline gave only 10,8 percent "very good" results but the "good" results represented 51,3 percent, indicating an increased efficiency of the new drug as compared with ampicilline. The serum levels of Amoxycilline (9,4 mg/ml after 2 hours, and 4,4 mg/ml after 4 hours), when a 0,5 g dose was given every 6 hours, assure a continuous and efficient bacteriostatic concentration. No significant adverse reaction were noted. PMID- 6248953 TI - [Clinico-radiological and functional correlations in endothoracic sarcoidosis]. AB - A total of 35 cases of endo-thoracic sarcoidosis have been studied, of which 18 were confirmed histopathologically on bioptic samples. The analysis of the cases revealed the predominance of young subjects. The reactivity of PPD on cutaneous testing was negative in 60 percent of the cases, in accordance with the antimycobacterial fluorescent antibodies test. The insidious onset and evolution are noted, and the fact that the diagnosis was made on the occasion of routine investigations. Correlation of clinical signs with the radiologic aspects did not reveal significant data, but correlation with functional tests has revealed in 8 out of 11 cases presenting with dyspnoea an alteration of the respiratory function (an obstructive, a restrictive or a mixed syndrome). The importance of the diagnosis is stressed, in view of the application of treatment, that should not be delayed. PMID- 6248954 TI - [Study of the indications for surgical treatment of pleuropulmonary tuberculosis at the present time]. AB - On a large personal experience basis the authors discuss the present stage of surgical treatment of pleuropulmonary tuberculosis. Stress is laid on the fact that, owing to technical surgical progress and continuous improving of equipments in the thoracic surgery departments, practically there are no contraindications for surgical treatment of pleuropulmonary tuberculosis provided the functional lung and heart parameters are satisfactory. It is emphasized too the requirement of a timely indication for surgery in cases of chemotherapy failures, prior to lung and heart function impairment. PMID- 6248955 TI - [False recurrences in pulmonary tuberculosis]. AB - A number of 170 relapses have been recorded between 1966 and 1975 in the sector nr. 1 of Bucharest. Of a total of 119 files that were examined a number of 11 false relapses have been selected. The authors stress the difficulties of a definite diagnosis when bacteriological confirmation in lacking, as well as previous radiological documents, and when sputum cannot be collected for bK examination. With regard to pulmonary tuberculosis involving the pleural cavity, repeated examinations of the pleural fluid are necessary, and especially pleural bioptic puncture. Relapses in pulmonary tuberculosis represent an epidermiometric index, and especially an index of efficiency of the anti-tuberculous therapy. Recording and reporting of these categories of patients is of particular importance in the evolution of the tuberculous endemy, and has special significance for the patient (that has to carry out a 12 month treatment with its social, economic and psychologic effects) and for the contact cases. PMID- 6248956 TI - [Dynamics of tuberculosis patients as revealed by the phthisiology offices of the Brasov district and reflected in the movement between dispensary groups]. PMID- 6248957 TI - [Paraneoplastic syndromes in bronchopulmonary cancer]. PMID- 6248958 TI - [Mechanical obstruction of the large intestine by wheat bran]. AB - Since a 1971 a high daily fibre intake has progressively won a place as therapy and prophylaxis for various diseases. Thus far there have been no reports of severe adverse side effects from high residue diet. Four patients are presented in whom wheat bran in the usual dosage caused mechanical obstruction in the lower rectum. PMID- 6248959 TI - N-Formylmethionyl peptide receptors on equine leukocytes initiate secretion but not chemotaxis. AB - The chemotaxis of leukocytes appears to be initiated by the binding of chemotactic factors to the surface of these cells. N-Formylated peptides induce chemotaxis and lysosomal enzyme secretion of leukocytes; because these peptides are available in a purified radiolabeled form, they have been useful in the characterization of receptors for chemotactic factors. Equine polymorphonuclear leukocytes secrete lysosomal enzymes but do not exhibit chemotaxis in respone to the N-formylated peptides, even though they have a high-affinity cell surface receptor for these agents. The specificity of the equine receptor resembles the specificity of the receptor on chemotactically responsive leukocytes from other species. Equine polymorphonuclear leukocytes may thus be an excellent model for the study of the events that lead to a biological response following receptor occupancy. PMID- 6248960 TI - Human hepatocellular carcinoma cell lines secrete the major plasma proteins and hepatitis B surface antigen. AB - Analysis of the cell culture fluid from two new human hepatoma-derived cell lines reveals that 17 of the major human plasma proteins are synthesized and secreted by these cells. One of these cell lines, Hep 3B, also produces the two major polypeptides of the hepatitis B virus surface antigen. When Hep 3B in injected into athymic mice, metastatic hepatocellular carcinomas appear. These cell lines provide experimental models for investigation of plasma protein biosynthesis and the relation of the hepatitis B viru genome to tumorigenicity. PMID- 6248961 TI - (-)Pentobarbital opens ion channels of long duration in cultured mouse spinal neurons. AB - Intracellular recordings from voltage-clamped mouse spinal neurons in tissue culture were used to study the membrane mechanisms underlying inhibitory responses to gamma-aminobutyric acid and the (-) isomer of pentobarbital. Fluctuation analysis suggested that both substances activated ion channels in the membranes. However, the channels activated by pentobarbital remained open five times longer than those activated by gamma-aminobutyric acid. PMID- 6248962 TI - Genetic variation in the human insulin gene. AB - Four recombinant lambda phages containing nucleotide sequences complementary to a cloned human preproinsulin DNA probe have been isolated from human DNA. Restriction analyses in conjunction with Southern hybridizations reveal two types of gene sequences. One isolate of each type was subjected to complete nucleotide sequence determination. The sequences contain the entire preproinsulin messenger RNA region, two intervening sequence. 260 nucleotides upstream from the messenger RNA capping site, and 35 nucleotides beyond the polyadenylate attachment site. Our results strongly suggest that these two gene types are allelic variants of a single insulin gene. PMID- 6248963 TI - [The 49 XXXXY syndrome. Report of a further case with leg ulcer and endocrine abnormalities (author's transl)]. AB - A 40 years old man with 49 XXXXY chromosomes is reported who has been suffering from a leg ulcer for many years. Clinical features were those usually seen in patients with the 49 XXXXY syndome. Low plasma testosterone level, elevated LH and FSH levels, and thyroid dysfunction wigh high peripheral blood TSH levels were the main endocrine anomalies in this patient. The association between the occurence of leg ulcers and sex chromosome anomalies is discussed. The endocrine dysfunction in this patient is compared to the endocrine features of Klinefelter's syndrome. PMID- 6248964 TI - [Hyperthyroidism and subjects hyperresponding to thyrotropin. Importance of simultaneous thyrotropin and prolactin determination following administration of thyroid-releasing hormone]. AB - Primary hypothyroidism is assessed by increased basal and TRH-induced TSH levels. Since basal and TRH induced prolactin (PRL) levels may also be modified by the thyroid status, TSH and PRL responses to TRH are simultaneously determined in patients with mild or evident primary hypothyroidism (n = 22) and in TSH hyperresponders (n = 28) with clinicobiological appearance of euthyroidism. In evident hypothyroidism (free thyroxine index FT4 I = 0,4 +/- 0,1) basal PRL are increased in 8 out of 11 patients and TRH-induced PRL responses are exaggerated in all cases like in mild hypothyroidism (FT 4 I = 1,2 +/- 0, 1) A negative correlation is found between maximal PRL levels and triiodothyronine (T3) levels (p less than 0,01). In presumed euthyroid TSH hyperresponders (FT4 I = 2,2 +/- 0,1) PRL response to TRH is exaggerated in only 7 patients and no correlation exists between maximal PRL and T3 levels. These data suggest that simultaneously exaggerated TSH and PRL responses to TRH are presumably patterns of potential hyperthyroidism for the diagnosis of which the determination of TSH alone seems to be necessary but insufficient. PMID- 6248965 TI - [Study of the fibrin degradation products in the synovial fluid of rheumatological diseases (author's transl)]. AB - FDP were studied in the synovial fluid of 23 patients with various rheumatological diseases. The levels, measured by the passive hemagglutination inhibition technique (Merskey technique), showed variable values, but were always found to be present. On half the cases a number of these molecules could be eliminated by a high dose of thrombin. Using three immune sera (anti-fibrinogen, anti-D, anti-E), immunoelectrophoresis revealed in half the cases one central nonmigrating arc and another with cathodic migration. This differs from results using FDP obtained by the digestion of fibrinogen by plasmin, but is, however, analagous with those obtained in vitro by the action of proteases of leukocyte origin. These results suggest that the intense fibrinogen catabolism within the pathological joints results from the action of proteolytic enzymes other than plasmin. PMID- 6248966 TI - [Angiographic signs of extra-dural hematomas of the posterior fossa (author's transl)]. AB - Traumatic subacute and acute extra-dural hematomas of the posterior fossa are infrequent lesions which can be considered as exceptional From 1973 to 1977, we have collected 12 such cases. We performed 11 carotid angiographies and 7 vertebral angiographies in the series. Only in one case among 5 did clinical signs suggested a lesion of the posterior fossa. One of the best clinical elements to suggest such a lesion is the presence of a fracture line that crosses the lateral sinus, which necessitated a complete angiographic study. Arteriographic signs are function of the topography of the hematoma. The carotid angiography reveals only the supratentorial extension of the extra-dural collection of the blood clot. The most frequent sign is a filling defect of the affected sinus. The classic sign of detachment of the torcular is seen only in about 25% of cases. Vertebral angiography shows the existence of an expanding posteroinferior mass of the posterior fossa. Axial views always permits to find the avascular zone which corresponds to the extra-dural collection of the blood clot. In addition, vertebral angiography permits a good study of the sinusal drainage of the posterior fossa. In the purpose to find a supra-tentorial extension the prognosis of the extra-dural hematoma depends on its early discovery. The procedure of choice to make and to confirm such a diagnosis is vertebral angiography and it is not necessary to perform a carotid angiography in the cases where a supra-tentorial lesion does not seen associated. PMID- 6248967 TI - [Value of intra-uterine washing in cytologic diagnosis of endometrial lesions (author's transl)]. AB - A cyto-histological correlation, according to the Gravlee Jet procedure, is proposed about 86 intra-uterine abnormal washings. In a series of 53 positive for cancer and 6 suspicious cytologic diagnosis, the pathologic study evidenced the cancer in 54 cases. In 2 cases, a cancer was discovered only by tissue section. According to the results and although there are some difficulties, this method of diagnosis of the upper feminine genital tract cancer seems to us valuable. PMID- 6248968 TI - [Diverticula of the duodenal window. 36 cases (author's transl)]. AB - The authors have studied 36 cases of duodenal diverticula detected during 500 biliary operations. Initial pre-operative diagnosis was based on upper gastrointestinal barium series alone. Fiberopticduodenoscopy was unable to detect the diverticula. Patients were studied by cholangiocinesimetry. This technic demonstrated that oddian activity was satisfactory, with normal sphincter pressures and thus eliminated any suspicion of odditis. In this series, diverticula of the duodenal window lead to no more complications than do cholelithiasis, acute cholecystis or acute pancreatitis. The repercussion of the diverticula seems then to be limited to isolated dilatation of the common bile duct. In treating, the authors conclude that, in case of common bile duct dilatation, external drainage or biliodigestive anastomosis is recommended. Sphincterotomy is not indicated. All direct surgery on the diverticula, responsible for heavy morbidity and mortality rates, is to be avoided. PMID- 6248969 TI - [Fistula between right pulmonary artery and left atrium. A case report and review of the literature (author's transl)]. AB - The communication between right pulmonary artery and left atrium is a very uncommon cause of right to left shunt. The 18th case in the world literature and the first case in France is reported here. Normal pressure in the right cavities and in pulmonary artery is evocative. Angiography assesses the diagnosis and precises the place and connections of the fistula. Surgical closing of the fistula must be promptly achieved in order to obviate embolic complications. PMID- 6248970 TI - [Value of urgent ultrasonography after renal injuries. A report on 12 cases (author's transl)]. AB - The results of ultrasonography recordings carried out urgently in 12 patients after renal trauma are used by the authors as a basis for outlining the ultrasonography features discovered in post-traumatic renal lesions, and for discussing the value and place of this examination in overall investigations of these lesions. Ultrasonography findings are compared with those of intravenous urography, and in certain cases with those of arteriography. Ultrasonography appears to be indispensable in many cases in order to confirm intravenous urography results, to complement them, and possibly to make up for their deficiencies. It is of particular value in 2 conditions: a) renal artery thrombosis, in which case it is the only examination capable of supplying information on the parenchyma, b) benign renal contusions which may not appear on intravenous urography. PMID- 6248971 TI - [Bone scan in the diagnosis of infectious osteoarthritis (author's transl)]. AB - Bone scan with Technetium 99m is harmless method of evaluation of skeletal lesions. It is safe in pediatrics age group and it can be used in early diagnosis of infectious osteoarthritis. Bone scan differentiate osteomyelitis from cellulitis, and also it may help in diagnosis of subclinical involvement of rheumatoid arthritis, benign and malignant bone tumors, stress fractures and periositis. We report results of bone scan in 30 pediatric patients as follows: osteomyelitis 9 cases, cellulitis 4 cases, infectious arthritis 4 cases, tuberculous osteoarthritis 2 cases, rheumatoid arthritis 2 cases, and other different diseases 9 cases. PMID- 6248972 TI - [Traumatic rupture of testis]. AB - A case of traumatic rupture of the testis is reported. The importance of early operation is stressed. PMID- 6248973 TI - [Immunology today]. AB - This review covers a large range of dynamic interactions between the genes, molecules and cells of the immune system, which define the conditions of its function and enable a balance to be found between the individual and his environment. The complexity and the flexibility of the system offer alternative or compensatory routes in case of deficiency. This does not become apparent unless the lesion is deep. PMID- 6248974 TI - [Astrocytic origin of a granular cell tumor of the cerebral hemispheres. Preliminary study of a case (author's transl)]. AB - A case of intracerebral granular cell tumor is described in a 64 year-old woman. The originality of this study comes from the histological and histochemical evidence of its astrocytic origin. The authors also include clinical, pathological and histogenetic comments about this tumor. PMID- 6248975 TI - [Serum lipids in correlation with the localizations of atherosclerosis. A preliminary statistical study of 1 511 cases (author's transl)]. AB - The frequency and nature of abnormalities of serum lipids have been studied in 1 511 patients in correlation with the localizations of atherosclerosis. The mean cholesterol concentration was significantly increased in coronary heart disease and mean triglyceride concentration was significantly increased in peripheral vascular disease. Mean values of R1 and B3 were higher in coronary heart disease, lower in cerebrovascular disease than in healthy subjects. PMID- 6248976 TI - [Acute asphyxia caused by a benign tumor of the bronchus (2 cases: a papilloma and a plasmocytoma)]. PMID- 6248977 TI - [Pyoderma gangrenosum and chronic myeloid leukemia. Two new cases (author's transl)]. AB - Two new cases of pyoderma gangrenosum with chronic myeloid leukemia are described and added to three others of the literature. Pyoderma gangrenosum is often bullous, painful and progresses quickly. It seems to have a bad prognosis in myeloid leukemia as in polycythemia vera, in which it appears lately as an evolution to myelofibrosis or acute leukemia transformation. Chemotactic disorders of polynuclear may be the main etiological factor in these cases. PMID- 6248978 TI - [Current data on inflammation. II. Role of the macrophage, pharmacology and anti inflammatory therapy]. PMID- 6248979 TI - [The association tretinoin-erythromycin base: a new topical treatment for acne. Results of a multicentric trial on 347 cases (authors transl)]. AB - A multicentric trial involving ten dermatological departments was conducted to evaluate the efficacy and tollerance of ANTIBIO-ABEREL (an association of Tretinoin and Erythromycin base) in 347 patients with persistant acne. Complete healing or considerable improvement was obtained in 85% of cases. This new treatment was active against both inflammatory lesions (papules and pustules) and retentional elements (microcysts and open comedones). It was also rapidly active, as very favorable results were obtained in ten weeks or less, in more than half of the cases. The tolerance was remarkable (less than 1% of cases had to interrupt treatment). This product represents an important progress as compared to Tretinoin alone. No other local or systemic therapy, especially long term antibiotherapy, is required. PMID- 6248980 TI - [The rheopneumography (author's transl)]. AB - The rheograph electrodes, placed in three symetrical leads on the axilla lines, permit recordings to be made of respiratory curves and, during respiratory apnea, of arterial pulmonary curves. The curves were recorded on 296 subjects who were either normal or attacked by lung or pleura diseases. In pathological cases, the respiratory enlargement can be validly reduced; an arterial pulmonary curve can be flattened and show abnormalities that attest to arterial compression (more particularly in cases of lung cancer or pleurisy), to the superposition of a cardiac or systemic arterial curve. An arterial curve can be replaced by a cardiac curve in cases of back-flow or attraction by the heart, an absence of parenchyma between the heart and the paries of the thorax. Information given by this method can be compared but not super imposed with those given by isotopic scanning. PMID- 6248981 TI - [Low 25-hydroxy-vitamin D (25-OH-D) plasma levels in pathology (author's transl)]. AB - Between october 1976 and march 1978, 160 patients with low 25-OH-D plasma levels were observed (25-OH-D less than 7 ng/ml). In this population, a high frequency of asthenia, anorexia, vertebral demineralization were noticed. Mean plasma level of calcium was significantly lower than controls. Mean plasma level of alkalin phosphatases was significantly higher than controls. These patients presented a varied pathology. These diseases were probably responsible for the low 25-OH-D plasma level. The mechanisms were varying, but anorexia and sun exposure defect were likely the main cause of the low 25-OH-D plasma level. PMID- 6248983 TI - [A prognostic study of 238 cases of chest trauma. Influence of the delay in admission in an intensive care unit (author's transl)]. AB - 238 cases of chest trauma were studied according to the same protocol. With this protocol we can perform on the one hand a comprehensive study of the prognosis according to the thoracic lesions and associated lesions and on the other hand a prognostic study according to the delay of admission in a intensive care unit. All our data show that the most serious lesion is the pulmonary contusion and that mortality increases if an associated lesion is present, according to its nature. On the other hand a comparison was performed between the patients directly admitted in the intensive care unit (GI) and the patients hospitalized after a delay (GII) this comparison shows that in G II patients the rate of complications was higher, the mortality more important and respiratory sequelae more frequent than for patients of GI with thoracic lesions of the same importance or less important. These data show that an early admission of chest trauma patients in an intensive care unit is desirable and that the duration of this hospitalization must be at least 3 or 6 days. PMID- 6248982 TI - [Calcium nephrolithiasis and phosphate therapy. Long term study (65 cases) (author's transl)]. AB - Protected phosphate therapy was used in 65 cases of recurrent calcium nephrolithiasis. Mean duration treatment was 2 years and 1 month (more than 3 years in 17 cases). Mean lithiasis episodes by year-patients were 1,55 renal colics and 0.34 stone formation before phosphate treatment, versus 0.66 renal colics and 0.10 stone formation (more than 60% reduction), during treatment. There was simultaneously decrease of hypercalciuria (24 cases out of 42), of asthenia (16 cases out of 19), of signs of spasmophilia (12 cases out of 18) and disappearing of bone pains (4 cases out of 6). Side effects were rare. Minor digestive troubles were observed in 11 cases: diarrhea (3 cases) or gastralgias (9 cases). These side-effects necessitated discontinuation of thiazide therapy in only two cases and reduction of doses in 6 other cases. From our data, phosphate therapy appears an efficient drug in recurrent calcium nephrolithiasis. It acts in reducing levels of calciuria and enhancing urinary pyrophosphates excretion, inhibitors of calcium crystallization. PMID- 6248984 TI - [Obstructive anuria (author's transl)]. AB - In the last 10 years we observed 75 cases of obstructive anuria: 60% during the course of pelvic cancer; 27% took place on a remaining kidney; 26% were due to kidney stones, usually uric acid stones; 3 cases were secondary to remaining kidney hydronephrosis. Diagnosis was facilitated by high dose, late film IVP and by descending uteropyelograms, one of the most reliable diagnostic techniques in trigonal obstruction. Hemodialysis was used in 10% of the cases. Early surgical treatment was often made possible by the use of spinal anesthesia. PMID- 6248985 TI - [Evaluation of the criteria used for the interruption of treatment in bacterial meningitis (persistent pleocytosis and hyper-cervicospinal fluid proteins (author's transl)]. AB - Among 809 patients with bacterial meningitis persistent pleocytosis greater than 60 white blood, cells/mm3, after 10 days or more of therapy, was found in 25 patients and persistent hypercervicospinal fluid proteins greater than 70 mg/dl in 24. In 14 patients there was an association of these disturbances. All cases, except one, were adequately treated. Persistent pleocytosis and hyper cervicospinal fluid proteins, uncommon inmeningococcal meningitis, were frequent in pneumococcal and more frequent in Haemophilus influenzae meningitis. In pneumococcal and Haemophilus influenzae meningitis the incidence of neurologic sequelae was greater in patients with persistent pleocytosis and hyper cervicospinal fluid proteins than without them. In adequately treated patients, persistent pleocytosis or hyper-cervicospinal fluid proteins alone cannot be used as an indication of prolonging or changing therapy of bacterial meningitis. PMID- 6248986 TI - [Bilio-digestive fistulae of lithiasic origin. A report of seventeen cases (author's transl)]. AB - 17 spontaneous bilio-digestive fistulae of lithiasic origin have been regrouped for study. 15 cases underwent operation and represent 1.3% of concomitant biliary diseases treated by surgery. The different symptomatic aspects are considered; biliary disorders have been found in 50% of the cases; concurrently, the frequent occurrence of biological cholestasis along with lithiasis of the common bile duct is emphasized. Preoperative diagnosis is usually established on discovery of aerobilia sometimes revealed only by X rays centred on the upper-right quadrant of the abdomen. These fistulae are in most cases cholecystoduodenal. The serious consequences of surgical treatment of biliary lesions and suture of the digestive tract seem to be related to age, usually advanced. Particular study is devoted to endoscopy both towards diagnosis and, in certain cases, therapeutic. PMID- 6248987 TI - [Behcet's disease with renal manifestation. One case followed up for 6 years (author's transl)]. AB - One case of Behcet's disease with renal manifestations was reported. The patient had muco-cutaneous manifestations, uveitis and neuro-Behcet. Renal involvement consisted in macroscopic hematuria and vasculitis at the histologic study; its prognosis was good, renal function was maintained after an evolution of six years and a second histologic study showed no modifications. PMID- 6248988 TI - [Primary lymphosarcoma of the lung secreting immunoglobulin (author's transl)]. AB - A case of primary lymphosarcoma of the lung with monoclonal seric dysglobulinemia of IgM type is reported in a 48-year-old man. This bilateral tumour consisted of lymphocytes with some plasmacytoid and plasma-cells. There was no bone, liver or lymph node involvement. A 3-year follow-up shows clinical remission with continuous chlorambucil therapy. The interest of the observation lies in the rarity of secretory lymphosarcoma of the lung: only five cases have been reported. Nosologic and diagnostic problems of lymphocyte and plasma cell proliferations in the lung are discussed. The difficulty to differentiate diffuse hemopathy from localized lymphoma and tumour from pseudo-tumour is emphasized. PMID- 6248989 TI - [Acute respiratory distress syndrome (ARDS) in cerebral malaria (author's transl)]. AB - Non hemodynamic pulmonary edemas included by some authors in the acute respiratory distress syndrome (ARDS) had been reported in cerebral malaria. We describe a new case. Clinical data, hemodynamic studies with PWP measurement, and anatomic findings are coherent with the diagnosis of ARDS. Although the underlying causal mechanisms--the marked parasitemia and its consequence on permeability of the pulmonary capillary--remain speculative, they seem credible. The pulmonary lesions are provoked by these main factors and worsened by hypoprotidemia and surinfection. Prevention of all these factors can stop the evolution towards refractory hypoxemia but the precocity of quinine treatment remains the most important point. PMID- 6248990 TI - [Caecal perforation in a patient with Sezary syndrome treated by corticosteroids (author's transl)]. AB - The authors report of a case of caecal perforation in a patient with Sezary syndrome who was submitted to systemic corticosteroids a few days before that complication. Caecal perforations during corticosteroid treatment appear to be rare, the known causes being essentially carcinoma, ischaemia and colectasia in inflammatory colitis. In the case reported, there was no associated intestinal lesion. The prognosis is usually severe, mainly on account of the lack of explicit symptoms. PMID- 6248991 TI - [Orthostatic increase in blood pressure in the elderly (author's transl)]. AB - In a systematic study of orthostatic changes in blood pressure involving 200 unselected patients of an old people's home (mean of age: 80 years), an orthostatic fall in blood pressure, which was almost always moderate and with no detectable clinical consequences, was found in only 14% of patients. On the other hand an orthostatic increase in blood pressure, which still persisted 15 minutes after maintaining the upright position was observed in 55% of these cases. The proportion of cases in which an orthostatic increase in blood pressure was found was not essentially different in the 121 patients considered as normotensive in supine position (i.e. 59%) and in the 79 patients initially hypertensive (i.e. 48%). The occurrence of such an orthostatic hypertension in the elderly, particularly in those considered as normotensive, does not appear to have been reported previously, but such disorder is likely to be associated with underlying physiological changes. It may be related to arteriosclerotic changes in the arterial walls which, in connection with the ageing process, cause a decrease in baroreceptor sensitivity. It may also be assumed that marked and persisting orthostatic increase in blood pressure favors or worsens preexisting arterial lesions, particularly in the brain, and that in such cases appropriate adrenoceptor blocking therapy would therefore be justified. PMID- 6248992 TI - [Digestive localization of generalized amyloidosis: attempt of differentiation of "primary" and "secondary" amyloidosis (author's transl)]. AB - The aim of this study is to precise topography of amyloid deposits in the alimentary tract and to differenciate the primary or secondary nature of amyloid substance according to these topographical data and with the help of the Wright's technic. The material of this study consists in nine necropsies and seventeen digestive biopsies, concerning patients with generalized amyloidosis. Immunoglobulinic amyloidoses (so-called "primary") contain predominating deposits in the muscularis propria which remain after Wright's technic. On the other hand, in the non-immunoglobulinic amyloidoses (so-called "secondary"), deposits are essentially localized in the mucosa and disappear (more than 80%) after Wright's technic. Moreover, some special cases, as Portugese amyloidosis and amyloidosis in the course of Crohn's disease, are studied. In the first case, the immunoglobulinic nature of amyloidosis seems to be very likely. In Crohn's disease, in one case, the classical notion of non-immunoglobulinic amyloidosis is confirmed, while, in another one, the amyloidosis is much likely an immunoglobulinic one, and that is a new fact. The authors insist on the practical aspect of this study: it is usually possible to precise the nature of the amyloid deposit on digestive biopsy and so, to give indications to the clinicians about an etiological group. PMID- 6248994 TI - The issue of structured coexistence of scientific and alternative medical systems: a comparison of East and West German legislation. PMID- 6248993 TI - Pyrophosphate myocardial imaging. PMID- 6248995 TI - Factitious trophoblastic disease: Munchausen's mole. PMID- 6248996 TI - [ECG tracing in electric injuries and subsequent burns complicated by chest contusion and anaerobic septicemia]. PMID- 6248997 TI - Collagen biosynthesis in healing wounds of the spinal cord and surrounding membranes. AB - Kinetics of collagen synthesis and deposition were studied in the canine spinal cord, pia mater, and dura mater and in wounds of these tissues over the first 8 weeks. Little collagen is present in unwounded spinal cord compared with surrounding mesenchymal membranes. Collagen synthetic potential was found within the spinal cord, a tissue of neurectodermal origin. Rate of collagen synthesis per collagen content in the unwounded spinal cord was high. This synthetic rate was as high as that of wounds at their maximum collagen synthetic rates. Substantial deposition of collagen followed spinal cord wounding. Wounding the spinal cord, pia mater, and dura mater caused substantial elevations in rates of collagen synthesis in each tissue. These synthetic rates remained at maximum levels throughout the 8-week study, a prolonged period when compared with other wounded tissues previously studied. The role of mesenchymal tissue physiology in central nervous system wound healing is discussed. The potential value of these findings for further studies and for experimental manipulation of the healing process in spinal cord and central nervous system wounds is presented. Implications of these findings on the hypothetical relationship of scar to spinal cord and central nervous system regeneration are noted. PMID- 6248998 TI - [The simple and the extended diagnosis of urinary calculi]. PMID- 6248999 TI - [Inhibitors of crystallization and calcium nephrolithiasis]. PMID- 6249000 TI - Immunologic sensitization and pulmonary hypersensitivity by repeated inhalation of aromatic isocyanates. PMID- 6249001 TI - Polybrominated biphenyl: acute and chronic effect on iron absorption and benzo(a)pyrene hydroxylase. PMID- 6249002 TI - The effects of delta 9-tetrahydrocannabinol and nabilone on the isolated guinea pig bronchus. PMID- 6249003 TI - Immunological consequences of transplanting rat insulinomas. AB - We investigated the genetics of transplanting a NEDH rat insulinoma in various donor-recipient combinations. The insulinoma survived indefinitely when it was transplanted in the NEDH strain. Mean survival times of 8.6 +/- 1.2 and 3.3 +/- 1.0 days were recorded in allogeneic and xenogeneic combinations, respectively. No prolongation of mean survival time was found when the rat insulinoma was first passed through the athymic nude mouse and then transplanted as either an allograft or xenograft. The findings of the major histocompatibility antigen (Ag B7) on the original insulinoma and the tumor that had been passed through the nude mouse demonstrates no demonstrable loss of transplantation antigens during passage. PMID- 6249004 TI - Comparison of various methods of chemical immunosuppression in islet cell transplantation. PMID- 6249005 TI - Cyclic nucleotides in immunosuppression--neuroendocrine pharmacologic manipulation and in vivo immunoregulation of immunity acting via second messenger systems. PMID- 6249006 TI - Eating more fats and oils as a step towards overcoming malnutrition. PMID- 6249007 TI - [Percutaneous puncture of renal cysts for diagnostic and therapeutic purposes (author's transl)]. AB - Percutaneous needle puncture of space-occupying lesions is an innocuous procedure in the differential diagnosis of renal masses. In conjunction with intravenous urography, ultrasonography and CT-scan it is a method of considerable diagnostic value, which will lead to a nearly complete accurate diagnosis. In this study we will report our experiences with diagnostic and therapeutic puncture of renal cysts. The instillation of Lipiodol has been given up, since a follow-up study became impossible due to radiological problems. The diagnostic procedure to differentiate expanding lesions of the kidney and the technique of percutaneous needle puncture are described as well as indications for surgical exploration. PMID- 6249008 TI - Extrarenal and urothelial Wilms tumor. AB - Two patients with Wilms tumor are presented. One patient had a bilateral Wilms tumor with invasion of the right renal pelvis and proximal ureter. A second patient presented with a large Wilms tumor originating separate from and inferior to the left kidney. The histologic, therapeutic, and prognostic implications of these radiographic presentations are explored. PMID- 6249009 TI - Ruptured congenital mesoblastic nephroma: chemotherapy and irradiation as adjuvants to nephrectomy. AB - A neonate underwent nephrectomy for a congenital mesoblastic nephroma which was found to be ruptured at the time of removal. Two years after operation there is no evidence of recurrent tumor. Present evidence is that nephrectomy alone is adequate treatment for mesoblastic nephroma, but close observation is mandatory if rupture has occurred. Recurrence should be countered with adjunctive chemotherapy. PMID- 6249010 TI - Renal vein ligation in absence of vena caval obstruction. AB - This is a report of a patient whose left renal vein was ligated in the course of a right nephrectomy for a large Wilms tumor, in the presence of an unobstructed vena cava and without established venous collateral circulation. It would appear that even with sudden obstruction to venous outflow the left kidney can develop an adequate network of collateral venous drainage capable of supporting normal renal function. PMID- 6249011 TI - Delayed cutaneous hypersensitivity reaction: complication of lymphangiography. AB - An unusual delayed hypersensitivity skin reaction developed after lymphangiography to stage the patient's adenocarcinoma of the prostate. PMID- 6249013 TI - Comparison of the serologic reactions stimulated in calves by the present bovine viral diarrhea vaccine strains. PMID- 6249012 TI - Multilocular cyst of kidney with embryonic tissue. AB - A case of a multilocular cyst in a child is documented, and a brief review of reported cases of multilocular cysts in pediatric age groups is presented. These cases can be divided into two subgroups based on the presence or absence of embryonic tissue within the cysts. The significance of this embryonic tissue with regard to histogenesis and prognosis of the multilocular cysts is discussed. PMID- 6249014 TI - Passively transferred immunity to IBD following live vaccination of parent chickens by two different routes. AB - Vaccination of broiler breeder parents with live infectious bursal disease (IBD) vaccine by the oral route resulted in higher and more persistent quantitative gel diffusion precipitins than vaccination by intramuscular injection. All the progeny of the orally vaccinated parents had maternally derived IBD antibody (MDA) at hatching while MDA was detected in only 35 per cent of the progeny of the intramuscularly vaccinated parents. This MDA had disappeared completely at 14 and eight days respectively. Susceptibility to IBD challenge began at eight days in the first group and at one day old in the second. The age of 100 per cent susceptibility occurred at 19 and 11 days in the respective groups. PMID- 6249015 TI - [99mTc-pyrophosphate scintigraphy in the diagnosis of arthritis]. PMID- 6249016 TI - [Clinical x-ray diagnosis of giant-cell tumors of the vaginae tendinum]. PMID- 6249017 TI - [Glomus angioma of the ungual phalanx]. PMID- 6249018 TI - [Properties of the causative agents of viral diseases in calves (a review of the foreign literature)]. PMID- 6249019 TI - [Aerosol vaccination of poultry against pox]. PMID- 6249020 TI - [Protective medium for the lyophilization of the infectious bronchitis virus of hens]. PMID- 6249021 TI - [Effectiveness of the microencapsulated form of trivitamin]. PMID- 6249022 TI - Studies on the in vitro uncoating of poliovirus. III. Roles of membrane-modifying and -stabilizing factors in the generation of subviral particles. PMID- 6249023 TI - Physical map of coliphage N4 DNA. PMID- 6249024 TI - Effects of arabinofuranosylthymine on Epstein-Barr virus replication. PMID- 6249025 TI - Properties of herpesvirus-induced "immediate early" polypeptides. PMID- 6249026 TI - Similar frequencies of antigenic variants in Sendai, vesicular stomatitis, and influenza A viruses. PMID- 6249027 TI - A study of the epithelioid transformation of MC29-infected chicken embryo cells. PMID- 6249028 TI - Viral interference by defective particles of vesicular stomatitis virus measured in individual cells. PMID- 6249029 TI - Early interactions of foot-and-mouth disease virus with cultured cells. PMID- 6249030 TI - Recombination between endogenous and exogenous simian virus 40 genes. III. Rescue of SV40 tsA and tsBC mutants by passage in permissive transformed monkey lines. PMID- 6249031 TI - Murine mammary tumor virus deficient in the major glycoprotein: biochemical and biological studies on virions produced by a lymphoma cell line. PMID- 6249032 TI - Immunoprecipitation of polypeptides from hamster embryo cells transformed by herpes simplex virus type 2. PMID- 6249033 TI - The in vitro activation and further characterization of the bluetongue virus associated transcriptase. PMID- 6249034 TI - A high-resolution oligonucleotide map generated by restriction of poliovirus type I genomic RNA by ribonuclease III. PMID- 6249035 TI - Cloning of DNA fragments of the right end of phage mu and location of the HindIII, SalI, PstI, and BamHI restriction sites on the genetic map of mu. PMID- 6249036 TI - Induction of neutralizing antibodies by the coxsackievirus B3 virion polypeptide, VP2. PMID- 6249037 TI - Human fibroblasts transformed by the early region of SV40 DNA: analysis of "free" viral DNA sequences. PMID- 6249038 TI - Endonuclease-sensitive regions in SV40 chromatin from cells infected with duplicated mutants. PMID- 6249039 TI - Isolation and characterization of low-molecular-weight DNA-binding proteins from retroviruses. PMID- 6249041 TI - Adenovirus early region 1b gene function required for rescue of latent adeno associated virus. PMID- 6249040 TI - SV40 T-antigen-related surface antigen: correlated expression with nuclear T antigen in cells transformed by an SV40 A-gene mutant. PMID- 6249042 TI - [Antibodies to hepatitis A virus in the population of SAP Vojvodina]. PMID- 6249044 TI - [Case of coxsackie virus infection with multiple organ involvement]. PMID- 6249043 TI - [Clinical aspects and pathomorphology of infectious polyradiculoneuritis]. PMID- 6249045 TI - [Organization of radiologic-gynecological care from the gynecologist's viewpoint]. PMID- 6249046 TI - [Effect of methyl bromide on the German cockroach (Blatella germanica L.)]. PMID- 6249047 TI - [Modification of glucose resorption by bulk materials]. AB - 40 test persons were randomized for testing the influence on the glucose resorption by ballast substances. The four groups consisted of 10 persons with healthy metabolism, 10 diabetics with diet, 10 with maninil 5 and 10 with B insulin. The oral glucose tolerance test with 100 g glucose was used. The examination time after application of the test meal was 120 minutes. As ballast substances the hemicelluloses supercol (galactomannan) and manucol (sodium alginate) were tested. For comparison an examination with only 100 g glucose (experiment A) and one with a placebo substance (experiment D) were performed. Of supercol (experiment B), mannucol (experiment C) and of the placebo substance 20 g were added to the sugar solution. Using supercol we could get unequivocally lower mean blood sugar curves in non-diabetics and in all groups of diabetics compared with the examination without addition of substance and with addition of placebo. When manucol was used, a decrease of the mean blood sugar curves could be observed, however, not proved. Thus the swelling substance supercol leads to a retardation of the glucose resorption. PMID- 6249048 TI - [Ways in which chemicals can affect cholinergic nerve endings]. PMID- 6249049 TI - [Certain biocybernetic aspects of carcinogenesis]. PMID- 6249050 TI - [DNA of the herpesvirus group]. PMID- 6249051 TI - [Hypothalamic releasing hormones. II. Submicroscopic localization, mechanism of action, routes of release into the blood]. PMID- 6249053 TI - [Surgical treatment of primary lung cancer]. PMID- 6249054 TI - [Hair diseases in children]. PMID- 6249052 TI - [Biological basis of the effect of toad toxin on the body]. PMID- 6249055 TI - [Asymptomatic form of ratpox in laboratory rats]. PMID- 6249056 TI - [Distribution of antibodies to poliovirus in the children of a large industrial city]. AB - The results of prolonged dynamic observations on the state of herd immunity against poliomyelitis virus in an industrial city are given. The survey covered 1304 children. The data thus obtained, when synchronized according to years, seasons, the age of the surveyed children and the methods used in the survey, indicated that in every age group 20-30% of children had no antibodies to group I poliomyelitis virus and 30% of children had no antibodies to group III poliomyelitis virus. The geometrical mean of antibody titers to different types of the virus fluctuated from 1.8 to 4.6 log2, the lowest value being obtained for the titer of antibodies to type III poliomyelitis virus. During the whole period of immunological control (1974-1978) no mass circulation of poliomyelitis virus and no outbreaks of poliomyelitis were registered despite the fact that a considerable proportion of children having no antibodies to one or several types of the virus was constantly present among the most susceptible part of children. PMID- 6249057 TI - [Poliovirus infection in monkeys vaccinated with live Sabin vaccine]. AB - An account of the findings resulting from the study of experimental poliomyelitis in M. rhesus after several immunizations with Sabin live vaccine is given. The challenge of the vaccinated monkeys with the virulent strain of poliomyelitis virus, type I, was shown to result in the development of a disease with clinical and morphological characteristics typical of poliomyelitis in some of these monkeys. The incidence of the infection was found to decrease with the growth of antibody level in the blood of the monkeys. The virus was isolated from the tissues of the vaccinated animals showing the symptoms of the disease less frequently than from the tissues of the control animals. PMID- 6249058 TI - [Reflex therapy of vertebrogenic radicular pain syndromes]. AB - The authors analyse results of the treatment of 120 patients with vertebrogenic radicular pain syndromes by reflexotherapy, electropuncture, electroacupuncture and acupuncture, applied both alone and combined under conditions of a neurological department. Examination of the patients included a comprehensive analysis of neurological symptomatology and its variations in the time course of the treatment exercised according to a specially elaborated schedule of case history. Approaches to the choice of the most effective methods of reflexotherapy, depending on the extent of injury, intensity of the pain syndrome and the state of the vegetative nervous system are offered and the efficacy of the methods of reflexotherapy is clinically compared. PMID- 6249059 TI - [Recent achievements concerning primary liver cancer in the adult]. PMID- 6249060 TI - Hereditary spastic paraplegia with neurogenic bladder disturbances and syndactylia. AB - The present paper reports a family settled in the northern part of Norway, with a hereditary neurological disorder consisting clinically of spastic paraplegia associated with neurogenic bladder disturbances and syndactylia. Nine out of 22 members in three generations exhibit these clinical features. The bladder disturbances, being incomplete supranuclear bladder paresis (uninhibited neurogenic bladder), were the main complaint and occurred at an early stage of the disease. The family probably represents an unusual form of hereditary spastic paraplegia (HSP). The mode of inheritance is considered to be autosomal dominant. PMID- 6249061 TI - Light, fluorescence, and electron microscopic features of neuronal intranuclear hyaline inclusions associated with multisystem atrophy. AB - Light, fluorescence, and electron microscopic features of intranuclear hyaline inclusions of neurons associated with multisystem atrophy in a 21-year-old woman are described. The neuronal inclusions resemble Marinesco bodies on light microscopy but differ from the latter in their distribution, autofluorescence, and ultrastructure. They are widespread in almost all central, peripheral, and autonomic neurons and are generally larger than Marinesco bodies. The inclusions emit yellow-green autofluorescence with ultraviolet light between 470 and 530 nm of the spectrum and are ultrastructurally composed of haphazardly arranged, uniform, fine, straight filaments (8-9 nm in diameter). The neuronal inclusions have neither the ultrastructural feature of known viral inclusions nor are associated with virus particles. Their chemical nature and pathogenesis remain to be elucidated. PMID- 6249062 TI - Congenital cerebellar neuroepithelial tumor with multiple divergent differentiations. AB - A case of congenital cerebellar tumor is reported. The tumor is composed of a few incomplete tubular structures analogous to the neural tube, and of neuroblastic, mature ganglionic, astrocytic, ependymal and undetermined neuroepithelial cells. A tentative diagnosis of congenital cerebellar neuroepithelial tumor with multiple divergent differentiations is made: the histogenesis is discussed. From a histogenetic point of view this tumor is given the provisional name of matrix cell tumor. PMID- 6249063 TI - Ultrastructural changes in granulomatous myopathy. AB - Muscle biopsies from four middle-aged to elderly women with a 3--16-years' history of slowly progressive proximal muscle weakness showed non-caseating granulomas. Although two of them had clinical features suggestive of sarcoidosis, the other two had not. No distinct differences in the structural changes of these cases were noted by light or electron microscopy. The granulomas were comprised of epithelioid cells, Langhans type giant cells, lymphocytes, macrophages, and small numbers of plasma cells, monocytes, and mast cells. Some lymphocytes appeared to be transformed. The damaged muscle fibres were mostly located near the granulomas. Some of them were infiltrated by epithelioid cells, macrophages and mononuclear cells similar to lymphocytes. These cells were seen between the basement and plasma membranes of the muscle fibres. The muscle fibres showed various degenerative changes. Regeneration of muscle fibres was also observed. Filamentous intranuclear inclusions were present in two cases. PMID- 6249065 TI - Cell-mediated immunity to herpes virus type-1 in patients with recurrent corneal herpes simplex. AB - The proportion of T lymphocytes in the peripheral blood, their phytohaemagglutinin reactivity, and the leucocyte migration inhibitory effect of purified tuberculin protein were found to be equal in 25 recurrent corneal herpes simplex patients and 17 healthy individuals who had never suffered from clinically manifest herpes simplex virus (HSV) infection. Conversely, the HSV vaccine inhibited the leucocyte migration in the healthy group, but not in the recurrent herpes patients when the clinical symptoms were manifest. In 14 recurrent corneal herpes simplex patients, the examinations were repeated after a 3-month symptom-free period, and in these periods the patients corresponded equally to the healthy group in every respect. PMID- 6249064 TI - [Value of the determination of the beta subunit of chorionic gonadotropin in the follow-up and control of trophoblastic disease]. PMID- 6249066 TI - Effect of trisodium phosphonoformate and idoxuridine on experimental herpes simplex keratitis in immunized and non-immunized rabbits. AB - The effect of trisodium phosphonoformate (PFA) has been compared to that of idoxuridine (IDU) when applied topically in both liquid and ointment preparations on herpetic keratitis in rabbits. Trisodium phosphonoformate had a therapeutic effect but was not as effective as idoxuridine in the vehicles tested. This was seen with both herpes-immunized and non-immunized rabbits. A herpesvirus mutant inducing a PFA restant DNA polymerase was used to infect rabbit corneas. A comparison of the effect of PFA on the keratitis caused by this resistant mutant and the wild type herpesvirus indicates that the therapeutic effect of PFA on the herpes keratitis was due to an inhibition of herpesvirus DNA polymerase. PMID- 6249067 TI - Angiotensin-converting enzyme in uveitis and sarcoidosis. AB - Serum angiotensin-converting enzyme (SACE) was studied in a group of 29 sarcoidosis patients (among whom five had uveitis) and in 22 patients with non sarcoid uveitis. SACE was normal in all non-sarcoid patients and elevated in 62 per cent of the patients with sarcoidosis. Thus an elevated SACE is closely linked to sarcoidosis and may be a valuable tool in evaluating patients with uveitis in search of a sarcoid origin. PMID- 6249068 TI - Generalized cytomegalic inclusion disease in neonates and infants. AB - Cytomegalic inclusion disease (C.M.I.) is caused by the salivary gland virus which is species-specific, and characterized by formation of inclusion-bearing cells in various organs. From the view point of spreading, it is divided into the localized and generalized type. We studied 18 generalized cases of infants in whom inclusion-bearing cells were detected in more than three organs. As to the portal of entry and the time of infection, cytomegalic inclusion disease can be classified into three subgroups in infants; congenital form (2 cases), early acquired form (8 cases) and acquired form with other debilitating diseases (8 cases). PMID- 6249069 TI - Malignant transformation of adenoma in large intestine--especially on villous adenoma. AB - The incidence of 454 resected adenomas was histologically 87.8% of tubular, 7.7% of tubulovillous and 4.5% of villous adenomas, respectively. Eigtosigmoid region. Male to female ratio was 1 to 1.8, 1.5 to 1 and 1.8 to 1 for the villious, tubulovillous and tubular adenomas, respectively. Adenocarcinomas of large intestine consisted of 684 cases, 709 lesions and male to female ratio was 1 to 1.01. It should be considered that the adenomas in female may grow largely compared with those in male, with subsequent malignant transformation. Although the adenomas were found at the rate of 26.4% in the rectosigmoid region, 74.2% of the adenocarcinomas were found in this region, because the adenomas in this region grow largely compared with the other regions. Mucinous carcinomas were found in 33%, 23% and 9%, respectively, in the adenocarcinomas with remaining adenoma showing villous, tuvulovillous and tubular types. PMID- 6249070 TI - Histamine H2 receptor-mediated cyclic AMP formation in human platelets. AB - The influence of histamine on the level of cyclic AMP was studied in human platelets. A dose-related accumulation of cyclic AMP was obtained, culminating at about 10 microM of histamine. The response was blocked by the H2 antagonist cimetidine, but neither by H1 antagonists nor by alpha- or beta-adrenergic antagonists. The results suggest that histamine causes an accumulation of cyclic AMP in human platelets by stimulation of H2 receptors. Cyclic AMP accumulation is supposed to be associated with a depression of the platelet function, and a reduced platelet release reaction was actually demonstrated by our results. PMID- 6249071 TI - Effects of ethanol on human lymphocyte levels of cyclic AMP. In vitro: Potentiation of the response to isoproterenol, prostaglandin E2 or adenosine stimulation. AB - The effects of ethanol, acetone and dimethylsulfoxide (DMSO) were tested on the accumulation of cyclic AMP in human peripheral blood lymphocytes in vitro. Isoproterenol (1.0X10(-8) - 1.0X10(-4)M), PGE2 (3X10(-8)-3X10(-6)M), adenosine (10(-7) - 10(-4)M) and phenylisopropyladenosine (10(-8) - 10(-4)M) caused a dose dependent increase in cyclic AMP accumulation. Over the entire range of concentration of stimulating drugs, ethanol caused an enhanced accumulation of cyclic AMP. At temperatures between 15 degrees and 30 degrees the effect of ethanol rose with increasing concentration from 0.2-6%. At 37 degrees and 40 degrees, 6% ethanol had less stimulatory effect than 2% ethanol. The effect of ethanol was shared by acetone and to a minor extent by DMSO, and was present also when phosphodiesterase was inhibited by isobutylmethylxanthine. It is suggested that ethanol enhances adenylate cyclase activity as a consequence of altered cell membrane fluidity. Since the effects on cyclic AMP accumulation can be observed already at rather low concentration of the solvents they may be of toxicological significance. PMID- 6249072 TI - Effect of primycin on some electric properties of the frog skeletal muscle. AB - The effect of primycin, a guanidine-type antibiotic was studied on the electric properties and 42K+ uptake of the frog sartorius and semitendinosus muscle. Both in normal and choline chloride Ringer solution, primycin evoked a concentration and time dependent depolarization of the surface membrane of the muscle. This depolarization was significantly increased by Na ions. Primycin treatment was shown to evoke a dose-dependent decrease of the depolarization induced by 20 mM K+-Ringer. When the muscles were incubated in a Ringer solution containing choline chloride, during an incubation period of 30 min the uptake of 42K+ was decreased to 12% upon the exposure to 5 x 10(-6) mol primycin as compared to the control value. As the primycin-induced depolarization increased, the shape and amplitude of the action potentials elicited by square-wave electric impulses were altered and decreased, respectively. In sodium isaethionate Ringer 1--2 x 10(-6) M primycin induced a slow depolarization resulting in firing potentials. The results suggest that primycin depolarizes the surface membrane exclusively through the blockade of the resting K+ channels, the other phenomena being the results of this depolarizing effect. PMID- 6249073 TI - [Juvenile fibromatosis with cytoplasmatic inclusions]. PMID- 6249074 TI - Possible physiological role of ACTH-peptides in nociception. PMID- 6249075 TI - Studies on corticotrophin and somatotrophin releasing factors using the perfused isolated pituitary cell column. PMID- 6249076 TI - Circular dichroic study of beta-endorphin conformation induced by membrane acidic lipids. PMID- 6249077 TI - Enkephalin inhibition of adenylate cyclase activity in neuroblastoma N18TG2 cells: effect of sulfatide incorporation. AB - Potentiation of the morphine inhibition of adenylate cyclase activity in the neuroblastoma N18TG2 cell line after sulfatide incorporation has been observed previously and a similar sulfatide effect on enkephalin inhibition was investigated. Conditions for the sulfatide incorporation were defined. Though N18TG2 cells possess a high affinity for 3H-D-Ala2-Met5 enkephalinamide (14 nM), the met5-enkephalin was relatively inactive in inhibiting the intracellular cAMP level. The IC50 value for met5-enkephalin to inhibit the prostaglandin E1 (PGE1) stimulated cAMP product was 65 nM in N18TG2 as compared to the IC50 value of 3 nM in the neuroblastoma x glioma NG108-15 hybrid. Upon exposure of the N18TG2 cells to 22 microM of sulfatide in the growth medium for 6 hours, both the potency and efficacy of the met5-enkephalin in sulfatide treated cells were found to be 3.4 nM. The degree of potentiation was dependent on the quantity of CS added to the growth medium and the age of the culture. Furthermore, the sulfatide effect appeared to be at the adenylate cyclase complex. Basal and PGE1-stimulated adenylate cyclase activity in the cellular membrane was similarly affected by enkephalin after sulfatide incorporation. There was a lipid specificity, since in the group of lipids tested only CS and PC exhibited the potentiation effect. PMID- 6249078 TI - Inhibition of development of tolerance to morphine by a peptide related to ACTH. PMID- 6249079 TI - Recent studies on interaction between opioid peptides and their receptors. PMID- 6249081 TI - On the mechanisms of the simultaneous release of immunoreactive beta-endorphin, ACTH, and prolactin by stress. PMID- 6249080 TI - Characteristics of peptide and alkaloid opiate binding sites in brain and peripheral tissues. PMID- 6249082 TI - Phosphorylation of beta-lipotropin, beta-endorphin, corticotropin, and parathyroid hormone: a potential control for peptide processing. PMID- 6249083 TI - Neuromodulatory functions of the brain pro-opiocortin system. PMID- 6249084 TI - Oral loading with L-tryptophan may augment the simultaneous release of ACTH and beta-endorphin that accompanies periaqueductal stimulation in humans. PMID- 6249085 TI - A role for the opiate peptides that presumably coexist with acetylcholine in splanchnic nerves. PMID- 6249086 TI - Biochemical and autoradiographic evidence for type 1 and type 2 opiate receptors. PMID- 6249087 TI - Possible functions of the enkephalins. PMID- 6249088 TI - Adrenocorticotropic hormone (ACTH) in the central nervous system. PMID- 6249089 TI - Multiple CNS receptor interactions of ergot alkaloids: affinity and intrinsic activity analysis in in vitro binding systems. PMID- 6249090 TI - Bromocriptine in the medical management of acromegaly. PMID- 6249091 TI - The molecular architecture of ergopeptines: a basis for biological interaction. PMID- 6249092 TI - Selective influence of ergot alkaloids on cortical and striatal dopaminergic and sergotonergic receptors. AB - The ergot alkaloids studied do exert selective effects on monoamine receptor systems. Lisuride acts as a very potent stimulator of adenylate cyclase in cortical brain regions, and may function as a mixed agonist-antagonist at high concentrations. It is most likely that in cortex, lisuride effects both dopamine and serotonin receptors, but predominantly serotonin receptors coupled to adenylate cyclase. The antagonist molindone exhibits selectivity for cortical serotonin-stimulated cyclase versus dopamine-stimulated cyclase and may prove useful for further elucidating the sites of lisuride action. LSD interacts with serotonin-stimulated cortical adenylate cyclase at higher concentrations than are needed for lisuride stimulation but, nevertheless, at lower concentrations than for serotonin itself (2-4). Bromocriptine, lergotrile and ergonovine may also act as agonists in stimulating adenylate cyclase, but with considerably less potency, and with differences in regional specificity for this stimulation, from lisuride and LSD. Each of these ergots may act as a mixed agonist-antagonist at high concentrations. With respect to the regions studied, antagonist effects on cyclase appear to be more prominent in striatum than in the cortical regions. The greater specificity of lisuride for serotonergic cortical receptors should make this compound useful in further studies of this system. PMID- 6249093 TI - Interaction of dopaminergic ergot derivatives with cyclic nucleotide system. PMID- 6249094 TI - The analysis of marijuana cannabinoids and their metabolites in biological media by GC and/or GC-MS techniques. PMID- 6249095 TI - Interaction of hormones with receptors and alterations of these processes with age. AB - A variety of hormone receptor concentrations appear to decrease during aging. Such reductions seem to be closely, if not causally, related to reduced responsiveness. The receptors appear to be lost from target cells during aging. The simple loss of target cells from target tissues is not a sufficient explanation for decreased hormone concentrations, since we can observe these changes in static cell populations. Currently, we are attempting to elucidate the molecular and neuroendocrine mechanisms that are involved in these changes, and we would like to apply some of the mechanisms of hormone receptor control to these problems of altered responsiveness. PMID- 6249097 TI - Population doubling numbers in cells with genetic disorders. PMID- 6249096 TI - Changes in synaptic structure affecting neural transmission in the senescent brain. PMID- 6249098 TI - Hypertension, vasculature and aging. AB - Essential hypertension is the most common disease which develops with advancing age, and its complication, arteriosclerosis, seems to be an exaggerated form of aging process in the mesenchymal tissues. Our present investigation demonstrated that deposition of collagen fibers in vessel wall may represent one aspect of the aging phenomenon occurring in normal vasculature. PMID- 6249099 TI - Genetic disorders of male sexual differentiation. PMID- 6249100 TI - [Effects of gluco- and mineralocorticoid and ACTH on rabbits' ERG (author's transl)]. PMID- 6249101 TI - [Studies on herpes simplex keratitis in experimental animals. Viral spread and latent infection (author's transl)]. PMID- 6249102 TI - Effects of transportations, a high lactose diet and ACTH injections on the white blood cell count, serum cortisol and immunoglobulin G in young calves. PMID- 6249103 TI - High Z elements in human sarcomata: assessment by multienergy CT and neutron activation analysis. AB - "Tumor equivalent" phantoms containing inorganic salts (KH2PO4, CH3COOK, NaCl and Kl) were scanned on an EMI 5005 body scanner at 140 kVp, 28 mA; 120 kVp, 33 mA; and 81 kVp, 42 mA. Significant signal gain for the detection of higher atomic number elements by multiple energy scanning was noted. Certain sarcomas are known to accumulate high Z elements. Accordingly, excised specimens of various histologies of human sarcomata (chondrosarcoma, liposarcoma, and malignant fibrous histiocytoma) were scanned at 140 kVp and 81 kVp. Using selected areas of interest in the computed tomographic (CT) image to direct the in vitro biopsy of various regions of excised tumors, interesting correlations between the CT number variation and the respective, high Z elemental composition variation, as determined by thermal neutron activation analysis were observed. Further investigation with phantoms and excised sarcomata at 62 kVp and 42 mA suggested that dual energy CT scanning (at 140 kVp and 62 kVp) may be a method of monitoring "effective Z" and heavy element compositional changes. The authors are also attempting to develop these same low kilovoltage techniques as a method for the noninvasive clinical monitoring of an antisarcoma chemotherapeutic agent, cis diammineaichloroplatinum (11). PMID- 6249104 TI - Lung metastases from synovial sarcoma simulating granulomas. PMID- 6249105 TI - Unusual ring in liver cell adenoma. PMID- 6249106 TI - Computed tomography of colon carcinoma. AB - A review was made of 80 computed tomographic (CT) examinations of the abdomen and/or pelvis in patients with known carcinoma of the colon. These studies were obtained for evaluation of the initial extent of disease, delineation of the progression of disease, determination of the response to therapy, or location of possible recurrence. The sites of metastases are reported. The results support the routine use of CT in patients with colon carcinoma. PMID- 6249108 TI - CT of noncystic liver lesions: bolus enhancement. AB - The combination of rapid bolus injections of urographic contrast medium and timed sequential computed tomography (CT) scans permits recognition of different patterns of enhancement. In a series of 68 proven tumors of the liver, minimal enhancement was observed in 68% of the lesions, homogeneous positive enhancement in 9%, and complex patterns in 23%. Sequential scanning of these lesions demonstrated both early and late contrast enhancement. Early enhancement seems to be related to tumor vascularity, whereas delayed uptake may be caused by slow diffusion into an abnormally large extravascular space. Although the combination of bolus injection and serial scans seems very promising in the detection of solid liver tumors, the usefulness of the method is limited by present inability to study the entire organ sequentially. PMID- 6249107 TI - Differentiating hepatic abscess from tumor: combined 111In white blood cell and 99mTc liver scans. AB - Space-occupying lesions in the liver are usually seen as photon-deficient areas on 99mTc sulfur colloid liver scans, irrespective of the underlying disease. The results of combined 111In white blood cell scans and sulfur colloid scans in three patients in whom the clinical diagnosis was either cancer or abscess are described. In the first patient, the 111In scan showed increased uptake in a region of the liver where 99mTc sulfur colloid scan showed a negative defect. Abscess was diagnosed. In the other two patients, both 111In and 99mTc scans showed cold lesions and cancer was believed to be the most likely diagnosis. These diagnoses were confirmed by biopsy. It is suggested that simultaneous white blood cell scans and sulfur colloid imaging provide additional specificity in diagnosis of hepatic masses. PMID- 6249109 TI - Irregular fatty infiltration of the liver: diagnostic dilemmas. AB - Five cases in which fatty infiltration of the liver occurred in a nonuniform distribution involving predominantly the right lobe of the liver are reported. Such nonuniform fat deposition may cause serious difficulty in the interpretation of the sonographic examination. With extensive hepatic fat deposition, the natural tendency of the operator to adjust the sonographic equipment to display most of the liver as a uniform medium gray tone resulted in the display of the small, normal areas of the liver as apparently abnormal anechoic areas. CT correctly identified the fat-infiltrated areas. Confusion between metastases and fat deposition on this basis can be anticipated in future patients. PMID- 6249110 TI - Dynamic calibration of a continuous organo-isocyanate monitor for hexamethylene diisocyanate. AB - In 1978, NIOSH recommended new exposure standards for all diisocyanates. They are 5 ppb TWA for a 10-hour work shift and 20 ppb ceiling for a 10-minute period (or the equivalent microgram/m3). Recently, a new continuous reading monitor, which responds immediately to both aliphatic and aromatic diisocyanates, has become commercially available. This instrument factory calibrated for measuring toluene diisocyanate, has different responses for different diisocyanates. The monitor was dynamically calibrated to measure hexamethylene diisocyanate (HDI) against the recommended high pressure liquid chromatographic methods. The standard atmospheres of HDI were generated using permeation and an evaporation method. The monitor reading is 50% of the true concentration up to 50 ppb. Beyond that, the monitor reading reaches a plateau and the measured concentrations could be unreliable. PMID- 6249111 TI - Skeletal muscle amino acid metabolism in chronic uremia. AB - The kinetics and factors regulating acid release were studied in epitrochlaris preparations of control and chronically uremic rats. These data were correlated with abnormal glucose and glucose precursor kinetics of azotemic patients and the impact of hemodialysis on these precursor-product interrelationships. In chronically uremic rat skeletal muscle, a subsensitivity to catecholamines was evident. A 1000-fold greater concentration of epinephrine was required in uremic muscle to inhibit alanine release compared to control preparations. The dose response curve for cAMP formation stimulated by epinephrine was shifted 1 log unit to the right in uremic muscle and adenylyl cyclase stimulation by epinephrine was shifted 1 log unit. Using simultaneous primed-injection continuous infusions [U-14C]-alanine and [2-3H]glucose, rates of metabolite turnovers were calculated from the plateau portions of the specific activity curves. In 14 azotemic patients, alanine and glucose turnover rates were found to be increased 276 and 154%, respectively, over that of the control group of 17 subjects. Glucose production was found to be 3-fold greater. Hemodialysis decreased alanine turnover by 35% and glucose production by 19%. However, glucose turnover was not affected by dialysis. Although the percentage of glucose produced from alanine approached normal levels, the percent of alanine used for gluconeogenesis increased 60%. These studies demonstrate that abnormal carbohydrate metabolism in uremia is a result of multiple factors. Diminished response of adenylyl cyclase and decreased levels of cAMP contributes to, but does not entirely account for, increased amino acid release. The increased alanine synthesis in skeletal muscle supports glucose overproduction found in chronic azotemia. Hemodialysis ameliorates but does not fully normalize glucose and alanine metabolism and may actually introduce additional abnormalities. PMID- 6249112 TI - Evaluation of enhanced glucagon sensitivity as the cause of glucose intolerance in acutely uremic rats. AB - These studies were undertaken to evaluate the possibility that increased hepatic glucose output, secondary to enhanced glucagon sensitivity, contributes to the glucose intolerance of acute uremia. In order to accomplish this, we determined the effect of an infusion of glucagon (6 ng/kg per min) on hepatic glucose output from isolated perfused livers of acutely uremic and sham-operated rats. Hepatic glucose output by livers from sham-operated rats more than doubled during glucagon infusion. In contrast, hepatic glucose output did not increase when livers of acutely uremic rats were perfused with glucagon. Furthermore, glycogen content did not fall nor did urea formation increas when livers from acutely uremic rats perfused with glucagon. On the other hand, dibutyryl cAMP infusion led to a similar increase in hepatic glucose output by livers from sham-operated and acutely uremic rats. Furthermore, urea formation increased and glycogen content decreased when livers from acutely uremic rats were perfused with dibutyryl cAMP. These results indicate that livers from acutely uremic rats exhibit a diminished responsiveness to glucagon-induced glycogenolysis and gluconeogenesis, but respond normally to dibutyryl cAMP. Thus, an increase in hepatic glucose output, secondary to enhanced glucagon sensitivity, does not appears to contribute to glucose intolerance in acutely uremic rats. PMID- 6249113 TI - Hepatic cancer in Chinese: a chapter in "georgraphic pathology". PMID- 6249114 TI - Effect of electro-acupuncture on behavioral responses and plasma levels of ACTH and TSH in naloxone-induced morphine withdrawal in rats. AB - Acupuncture with electrical stimulation effectively suppresses naloxone-induced morphine withdrawal in rats and reduces the plasma levels of adrenocorticotropin and thyroid stimulating hormone. PMID- 6249116 TI - Radioimmunoassay for detection of antibody to hepatitis A virus. Results of clinical evaluation. AB - The performance of a solid-phase radioimmunoassay (HAVAB) for the detection of antibody to hepatitis A virus (HAV) was evaluated in clinical studies. The procedure was reproducible by eight investigators, and laboratory-to-laboratory variations were minimal. The sensitivity of the test was about equal to or slightly greater than that of immune adherence hemagglutination (IAHA) for detecting antibody in serum, but IAHA gives somewhat higher titer values than HAVAB. A survey of the incidence of anti-HAV in selected populations revealed an overall frequency of 48% and a correlation with age and lower socioeconomic status. The specificity of the test was demonstrated with specimens from patients who had clinical hepatitis A. Seroconversion to anti-HAV positivity was demonstrated with HAVAB to coincide with onset of illness, about two to three weeks earlier than it was detected by IAHA. HAVAB provided a convenient test for demonstrating the immune status of subjects, and was useful as an aid in diagnosing hepatitis A. PMID- 6249115 TI - Immunohistochemical demonstration of common antigen of polyomaviruses in routine histologic tissue sections of animals and man. AB - All polyomaviruses have a common antigen, which is located on the major capsid polypeptide (VPI). This antigen was demonstrated in routine histologic sections of formalin-fixed paraffin-embedded tissues by the peroxidase-antiperoxidase technic. Antiserum to the common determinant reacted with JC virus in oligodendrocytes of a patient who had progressive multifocal leukoencephalopathy, BK virus in bladder epithelium of a renal transplant patient, and K virus in endothelial cells of mouse lung. This method may be applicable to the screening of tissues for all polyomaviruses in diagnostic and investigative pathology. PMID- 6249117 TI - The prostaglandins. PMID- 6249118 TI - CSF eosinophilia during an acute coxsackie B4 viral meningitis. PMID- 6249119 TI - Bile duct carcinoma: a late complication of congenital hepatic fibrosis. Case report and review of literature. AB - Bile duct carcinoma is reported in a 50-year old man as a rare late presentation of congenital hepatic fibrosis (CHF). A survey of the world literature suggests that carcinoma occurs with increased frequency in congenital biliary dilatation. It appears to be a particular risk in patients with prolonged survival but is rare in CHF, where portal hypertension and renal insufficiency make the long-term prognosis poor. In this patient the absence of both gastroesophageal varices and renal disease may have permitted longevity with development of carcinoma. The finding of carcinoma arising in the bile ducts distal to the basic lesion of CHF suggests that active carcinogens may be present in the bile in CHF. The tumor in this patient was unusual in producing mucinous biliary obstruction and terminal hypercalcemia. PMID- 6249120 TI - Immunoglobulin M-specific serologic testing in an outbreak of foodborne viral hepatitis, type A. AB - Ninety-seven symptomatic and five asymptomatic infections with viral hepatitis, type A (102 cases) were identified in members, guests and employees of a private country club in an outbreak associated with consuming food and ice prepared or handled by an employee of the club's kitchen pantry. Twenty-three symptomatic persons were tested by differential radioimmunoassay for immunoglobulin M (IgM) (acute-phase) hepatitis A antibody (anti-HAV) and all 23 were documented to be infected with hepatitis A virus (HAV). Forty-one member/guest cases had only a single exposure at the county club. Their incubation periods ranged from 21 to 40 days, with a mean of 30 days. The exposure of these single-day patrons occurred over a 14-day period. The index case was not icteric and only moderately symptomatic and was diagnosed retrospectively to have viral hepatitis, type A by serologic determination of IgM anti-HAV in blood samples. Four items implicated in disease transmission were potato salad, hot dogs, molded salmon and ice handled by the index case. Serologic screening of controls did not appear to alter the conclusions of the food item analysis. PMID- 6249121 TI - Syndactyly: frequency of specific types. AB - Syndactyly without other combined limb anomalies, Poland complex, or amniotic bands, was diagnosed in 174 of 599, 109 consecutive newborn infants (3/10,000). Syndactyly was the only diagnosed anomaly in 133 cases, and it was associated with other anomalies in 41. The most common type of syndactyly was isolated syndactyly of the second and third toes (70 cases), which affected more males than females, and had a higher than expected frequency of white non-Latin European ancestry. The second most frequent type was isolated syndactyly of the middle and ring fingers (18 cases), and the third was isolated syndactyly of the fourth and fifth toes (13 cases). Considering both isolated and syndromal cases, 66% (114/172) could be assigned to one or another of the fourth genetic categories of syndactyly described by Temtamy and McKusick [1978]. This, plus the high frequency of affected first degree relatives observed (25/434:6%), suggests that the genetic forms of syndactyly may be more common than might be suspected from the small number of pedigrees in the literature. PMID- 6249122 TI - Corticosteroids and varicella disciform keratitis. PMID- 6249123 TI - Brain tumors. PMID- 6249124 TI - 25-hydroxyvitamin D3 metabolism by isolated perfused rat kidney. AB - Kidneys of adult rats were removed and perfused with semisynthetic media with the object of elucidating the separate actions of factors implicated as modulators of renal metabolism of 25-hydroxyvitamin D3 (25(OH)D3). During a 3-h perfusion with 3[H]25(OH)D3, the kidney produced high yields of 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) or 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) depending on whether the rat had previously been, respectively, normocalcemic, normophosphatemic, vitamin D-replete or hypocalcemic, hypophosphatemic, vitamin D-deplete. With longer perfusion (up to 12 h), kidneys from normocalcemic, normophosphatemic, vitamin D replete rats mainly produced 24,25(OH)2D3 but also amounts of 1,25(OH)2D3. This pattern was unaltered by reducing Ca or Pi concentrations of perfusate or by adding parathyroid hormone. Kidneys of hypocalcemic, hypophosphatemic, vitamin D deplete rats perfused with low Ca, low Pi medium for 12 h at first produced 1,25(OH)2D3 exclusively. However, 24,25(OH)2D3 appeared after 4 h and accumulated thereafter, whereas 1,25(OH)2D3 synthesis ceased after 7 h, a metabolic pattern unaffected by the concentration of substrate or end products in the perfusate or by addition of cyclic AMP. The model shows promise for studying regulation of 25(OH)D3 metabolism by the kidney. PMID- 6249125 TI - ACTH-elicited sodium appetite in sheep. AB - Intramuscular injections of long-acting synthetic ACTH (45 U twice daily for 5 days) caused a large increase in the intake of 0.5 M NaCl in sheep. Mean Na intake of the sheep on the last 3 days of treatment approximated 50% of their total extracellular fluid Na. The mineral appetite was specific for NaCl. Intakes of 0.5 M KCl or 0.25 M CaCl2 were not significantly altered. The enhanced appetite for Na induced by ACTH appeared to precede any increase in urinary Na excretion. ACTH treatment was ineffective in adrenalectomized sheep. However, an infusion into adrenalectomized sheep of a combination of adrenal steroid hormones (including aldosterone, deoxycorticosterone, 11-deoxycortisol, cortisol, and corticosterone) that contrived blood levels similar to those, obtained with ACTH treatment in normal sheep did induce Na appetite. Thus, ACTH induces a specific, adrenal-steroid hormone-dependent Na appetite in sheep. PMID- 6249126 TI - Calcium transport in small intestine during pregnancy and lactation. AB - The factors involved in calcium homeostasis during the mammalian reproductive cycle and specifically in the control of active calcium transport in the intestine have not been thoroughly investigated. For this reason calcium transport in the intestine was measured in vitamin D-replete and vitamin D deficient rats during pregnancy and lactation using the everted gut sac technique. In addition the changes in the plasma concentrations of calcium and 1,25-dihydroxyvitamin D were measured and correlated with transport. During the later stages of pregnancy and during lactation, the concentration of calcium in the plasma is reduced 10-30%. In turn, in the vitamin D-replete rat, the concentration of 1,25-dihydroxyvitamin D in the plasma increases from a control value of 26 pg/ml to 158 pg/ml at day 14 of lactation. Calcium transport in the intestine increases late in pregnancy, peaks during lactation, and then falls to control values by 3 wk postweaning in both vitamin D-replete and D-deficient animals. These findings strengthen the established relationship between 1,25 dihydroxyvitamin D and active calcium transport in the intestine as well as suggest that some factor(s) independent of vitamin D is stimulating intestinal calcium transport during the reproductive cycle. PMID- 6249127 TI - Down-regulation in vivo of PGE receptors and adenylate cyclase stimulation. AB - Down-regulation in vivo of liver plasma membrane receptors for prostaglandin E (PGE) was investigated in Sprague-Dawley rats using the 16,16-dimethyl analogue of PGE2, This analogue was used for subcutaneous injections because it escapes the rapid pulmonic degradation characteristic of PGE and was recognized well by liver plasma membrane receptors. Following treatment with the analogue, the concentration of PGE receptors was significantly decreased (-37%, P less than 0.001), but the binding affinity was not altered. There was no evidence for carry through of the analogue into the isolated plasma membrane preparation. It was also demonstrated that GTP decreased the binding affinity between PGE and its receptor. Down-regulation of receptor concentration was associated with a significant decrease (P less than 0.001) in PGE1-stimulated plasma membrane adenylate cyclase activity. These data provide the novel demonstration that rat liver plasma membrane receptor for PGE can be down-regulated in vivo and that this causes a corresponding decrease in PGE-induced plasma membrane adenylate cyclase activity. PMID- 6249128 TI - Blood-brain barrier transport and brain sequestration of steroid hormones. PMID- 6249129 TI - Use of a model of small bowel mucosa to predict passive absorption. AB - The purpose of this study was to determine if the observed rate of passive absorption of inert gases from the canine small bowel could be predicted by the use of an anatomical model of the mucosa and measurements of villus blood flow and the diffusive barrier to absorption. Villus blood flow was measured with microspheres and the diffusive barrier separating bulk luminal contents and blood was estimated from CO absorption. The model predicts initial uptake of the inert gases (H2, He, CH4, and 133Xe) in blood at the villus tip, subsequent countercurrent exchange in the villus, and longitudinal diffusion of the gases down the villus to a subvillus blood flow. Observed absorption rates for each of these four gases were reasonably accurately predicted by the model at both basal villus blood flow and at low villus blood flow induced by hypotension. We suggest that this model can be used to predict passive absorption kinetics over a range of villus blood flows and to predict the influence of a variety of parameters on the rate of passive absorption of diffusible substances. PMID- 6249130 TI - Projections to the hypothalamus from buffer nerves and nucleus tractus solitarius in the cat. AB - In 18 cats anesthetized with chloralose, electrical activity of spontaneously active hypothalamic units was monitored for changes in firing frequency during electrical stimulation of carotid sinus (CSN) and aortic depressor (ADN) nerves and the nucleus tractus solitarius (NTS). Stimulation of the CSN altered the activity of 55% (381/691) of the tested. These responsive units were widely distributed in the ipsi- and contralateral hypothalamus. Of the units tested during stimulation of the ADN only 6% (17/274) changed their firing frequency. Responsive units were located only on the ipsilateral side and primarily in the paraventricular and supraoptic nuclei, Electrical stimulation of the NTS altered the firing frequency of all 84 hypothalamic units previously identified by stimulation of the CSN. NTS stimulation elicited responses that had a significantly shorter latency and followed significantly higher frequencies of stimulation when compared to stimulation of the CSN. These results demonstrate that the two buffer nerves have distinctly different central projections to the hypothalamus and suggest different functional roles for the ADN and CSN in homeostatic regulatory mechanisms mediated by the hypothalamus. PMID- 6249131 TI - Sympathetic nerve rhythm of brain stem origin. PMID- 6249132 TI - Basis for 2-6 cycle/s rhythm in sympathetic nerve discharge. PMID- 6249133 TI - Coexistent lobular carcinoma in situ and intraductal carcinoma in a single lobular-duct unit. AB - Current classifications of mammary carcinoma generally divide noninvasive disease into two seemingly distinct categories: in situ lobular carcinoma and intraductal carcinoma. The two are considered to be independent entities which may sometimes coexist separately in the same breast. Three cases illustrated in this report each had classical histological changes of noninvasive duct and lobular carcinoma merging in single lobular-duct systems. The morphological separation of lobular carcinoma in situ and intraductal carcinoma may not be clear-cut in all cases. The existence of combined patterns may explain why some patients with untreated in situ lobular carcinoma subsequently develop invasive duct carcinoma. PMID- 6249134 TI - Small cell squamous and mixed small cell squamous--small cell anaplastic carcinomas of the lung. AB - Five patients are presented who had neoplasms which, by light microscopy and in two cases cytologically, appeared to be small cell anaplastic (polygonal and fusiform cell type) carcinomas of the lung. However, by electron microscopy, four of the carcinomas exhibited squamous characteristics including desmosomes and tonofilament bundles, and lacked demonstrable neurosecretory granules, suggesting that they were small cell squamous carcinomas. The fifth carcinoma contained cells with neurosecretory granules as well as cells demonstrating squamous differentiation. One patient died within 3 months of presentation. Three patients survived for approximately 18 months each; two received chemotherapy but one was treated by surgical resection alone. The fifth patient had a peripheral coin lesion which was treated by surgical resection only; he is alive without evidence of recurrent carcinoma 1 year after operation. We suggest that some carcinomas of the lung with the light-microscopic and cytologic appearance of small cell anaplastic carcinoma are actually small cell variants of squamous cell carcinoma and lack the characteristic neurosecretory granules of classic small cell carcinoma. The behavior of these tumors needs to be determined. PMID- 6249135 TI - Insulinoma in Seattle: 39 cases in 30 years. PMID- 6249136 TI - Immediate breast reconstruction after modified mastectomy for carcinoma of the breast. PMID- 6249137 TI - [Reaction of stress parameters during electrostimulation analgesia and neuroleptanalgesia (author's transl)]. AB - Surgical interventions produce a stress response in patients. Electrostimulation analgesia (ESA) has been described as a method yielding excellent results in poor risk patients. The present study was undertaken to investigate the stress response of ESA compared with neuroleptanalgesia (NLA). 30 female patients (16 with ESA, 14 with NLA) ranging from 34 to 55 years without endocrine, hepatic, renal or cardiovascular disease who were undergoing vaginal hysterectomy, were subjected to the study. The concentrations of cortisol, cholesterol and glucose in the plasma, the mean arterial blood pressure, the heart rate and the tension time-index were measured before and during anesthesia as well as during and after surgery. In patients receiving ESA the stress reaction seems to be more pronounced, judged by the higher level of plasma cortisol. The decrease of cholesterol as well as the increase of plasma glucose, mean arterial pressure, heart rate and tension-time-index supported this interpretation. During anaesthesia but before starting the operation the changes in the parameters showed that ESA induces a higher stress reaction than NLA. PMID- 6249138 TI - Simultaneous determination of vitamins A, D2 or D3, E, and K1 in infant formulas and dairy products by reversed-phase liquid chromatography. PMID- 6249139 TI - [Vitamin-resistant rachitism related to the X chromosome in adults. A report on three cases, one of whom had associated articular chondrocalcinosis (author's transl)]. AB - Three cases of X-linked vitamin-resistant rachitism and discovered in adult life are reported. In all 3 cases there were morphological anomalies affecting mainly the limbs which were incurved and reduced stature. In two of the patients the disorder was progressive and presented as pain, walking difficulties, and Looser Milkman striae. In the third case the hypophosphatemia was asympomatic, but it enabled the early diagnosis of a progressive rachitic disorder in the patient's child; treatment with 1-25 dihydroxycholecalciferol alone caused renewed growth, disappearance of radiological anomalies, and regression of biological disorders. Articular chondrocalcinosis was also present in one of the patients. This could be a coincidence and systematic search for this condition in cases of vitamin resistant rachitism will be necessary to establish a possible relationship between the two affections. PMID- 6249140 TI - The roles of calcium and cyclic AMP in cell proliferation. PMID- 6249141 TI - Junctional cell-to-cell communication and growth control. PMID- 6249142 TI - On the mechanism of Na+-dependent glucose transport. PMID- 6249143 TI - Anion and proton transport. PMID- 6249144 TI - Specific inhibition by "loop" diuretics of an anion-dependent Na+ + K+ cotransport system in avian erythrocytes. PMID- 6249145 TI - The role of bicarbonate ions and of adenosine 3',5'-monophosphate (cAMP) in chloride transport by epithelial cells of bullfrog small intestine. AB - In an HCO3-free medium, isolated segments of bullfrog small intestine, stripped of their external muscle layers, displayed a small, serosal positive PD that did not, on the average, differ significantly from zero. Similarly, in this medium, the mean values of Isc and of net Na+ and Cl- absorption under short-circuit conditions did not differ significantly from zero. External HCO3- (25 mM) induced a highly significant serosal negative PD and Isc and a large net absorption of Cl . Net Cl- absorption exceeded Isc, i.e., there was a significant net flux, JR, which was consistent with a net secretion of HCO3-. The ratio of the internal Cl activity of the absorptive cells (alpha Cli) to its equilibrium value was larger in the presence than in the absence of HCO3-. In the presence of HCO3-, cAMP, added to the serosal medium, reversed the serosal negative PD and Isc, and inhibited, though it did not completely abolish, net Cl- absorption. JR was unchanged; tissue Cl- and alpha Cli were reduced, and tissue Na+ decreased and tissue K+ increased. When HCO3- and Cl- were removed from the bathing medium, the electrical response of the tissue to cAMP, though greatly attenuated, was not completely abolished. Under these conditions, cAMP induced a significant net Na+ absorption. A model for ion transport in the absorptive cells of the small intestine is proposed that is consistent with these findings. PMID- 6249146 TI - The role of cyclic nucleotides and calcium in the regulation of chloride transport. PMID- 6249147 TI - Chloride active transport, membrane lipids and receptors in the corneal epithelium. PMID- 6249148 TI - Theories on gastric acid secretion. PMID- 6249149 TI - The functional role of K+-ATPase in proton transport by gastric microsomal vesicles. PMID- 6249150 TI - Aspects of parietal cell biology: cells and vesicles. AB - Many features of these gastric vesicles satisfy the requirements for the gastric H+ pump. For example, we have: (a) K+ requirement, (b) KA for K+ of about 30 mM; (c) identical cation sequence for tissue and vesicles, (d) similar anion sequence, (e) localization at the microvillus of the secretory canaliculus, (f) TI+ inhibiting H+ transport of both systems, and (g) the K+ gradient satisfying the osmotic gradient requirement for HCl-flow out of the parietal cell. Points that require explanation are lack of SCN- effects and regulation of KCl permeability. PMID- 6249151 TI - Transport ATPases in anion and proton transport. AB - Studies in our laboratory have shown that the anion-sensitive Mg-ATPase is located in mitochondria, but not in the plasma membrane of rabbit gastric mucosa, trout gill, rabbit kidney and rat pancreas; whereas in rabbit erythrocyte membrane, it is part of the Ca-Mg activated ATPase system. These findings appear to rule out a function of the anion-sensitive ATPase in the transport of anions and protons across the plasma membrane in these tissues. On the other hand, the K activated ATPase in a gradient-purified vesicle fraction of pig gastric mucosa mediates proton uptake in exchange for K+ in the presence of ATP, in agreement with earlier findings of other investigators. The enzyme requires a phospholipid environment for its activity. Studies of arginine modification with butanedione in the presence or absence of ATP and its analogues, and of activating cations indicate that the enzyme contains an essential arginine group involved in ATP binding; and that K+ induces a conformational change, which leads to decreased ATP binding and probably coincides with enzyme dephosphorylation. Similar studies of sulfhydryl modification with DTNB indicate that the enzyme contains an essential sulfhydryl group, which does not appear to be directly involved in ATP binding, but rather that ATP binding may induce a conformational change which makes the sulfhydryl group less accessible. PMID- 6249152 TI - The kinetics of the titratable carrier for anion exchange in erythrocytes. PMID- 6249153 TI - Transport and interactions of anions and protons in the red blood cell membrane. PMID- 6249154 TI - Reconstitution of the erythrocyte anion transport system: in vitro and in vivo approaches. PMID- 6249155 TI - The separation of apical from basal-lateral plasma membranes of epithelial cells: a tool to identify transport systems. PMID- 6249156 TI - Thermodynamic efficiency of cotransport mechanisms with special reference to proton and anion transport in yeast. PMID- 6249157 TI - Anion transport mechanisms in neurons. AB - Evidence has been presented and reviewed to show that chloride is often not in electrochemical equilibrium across neuronal cell membranes. An ATP- and sodium dependent uptake mechanism has been described for the squid giant axon. Finally, the role of chloride in the maintenance of pH1 has been discussed. Present evidence favors a net chloride extrusion being involved in the acid extrusion process. Measurements of free, ionized chloride levels in several neuronal cells have suggested that the transmembrane distribution of chloride does not conform to thermodynamic equilibrium conditions. Net extrusion of Cl- against its electrochemical gradient has been measured in the giant neuron of the Aplysia abdominal ganglion. In the squid giant axon, cellular Cl- levels are higher than predicted from passive thermodynamic considerations. An ATP requirement as well as a dependence upon extracellular sodium has been demonstrated for chloride influx. Similarly, there is an ATP-, external Cl-dependent, Na+ influx. Thus, an ATP-requiring Na-Cl cotransport mechanism appears to account for the high cellular chloride content of the squid giant axon. Chloride efflux from several neurons appears to be involved in the regulation of intracellular pH (pHI). When pHi is made acidic, chloride efflux from the squid giant axon increases and this stimulation requires cellular ATP and external HCO3-. When pHi is measured following an acid load, it is found that pHi recovery toward normal values requires cellular Cl-, ATP and external HCO3-. Thus, an exchange process between cellular Cl- and extracellular HCO3- appears to play an important role in pH1 regulation. Such a process appears to be responsible for the lower-than equilibrium levels of chloride found in certain neuronal cells. PMID- 6249158 TI - A voltage-dependent chloride conductance channel from Torpedo electroplax membrane. PMID- 6249159 TI - Structure and mode of action of a voltage dependent anion-selective channel (VDAC) located in the outer mitochondrial membrane. AB - VDAC is a channel-forming protein, located in the outer mitochondrial membrane, whose properties are consistent with the known permeability behavior of that membrane. When extracted with Triton X-100, VDAC exists as a 110,000 molecular weight glycoprotein complex which is a prepackaged channel. When inserted into liposomes, the permeability increase to non-electrolytes is consistent with a pore radius of 20. In a planar lipid bilayer, VDAC is anion selective and voltage gatable. This suggests that the permeability pathway in the outer mitochondrial membrane might be under physiological control. Many of VDAC's properties are qualitatively very similar, although quantitatively different, to those of porin, the channel responsible for the permeability of the outer membrane of at least some gram negative bacteria. PMID- 6249160 TI - Protonmotive cytochrome system of mitochondria. PMID- 6249161 TI - Respiration-coupled H+ ejection by mitochondria. PMID- 6249162 TI - Functional organization of proton and bicarbonate transport in turtle urinary bladder. PMID- 6249163 TI - Protein precursors in the assembly of yeast cytochrome c oxidase, a transmembranous oligomer of the inner mitochondrial membrane. PMID- 6249164 TI - Proteolytic events in replication of animal viruses. PMID- 6249165 TI - Synthesis and assembly of viral membrane proteins. PMID- 6249166 TI - Studies of cloned DNA encoding the structure for the bovine corticotropin-beta lipotropin precursor protein. PMID- 6249167 TI - The structure of rat preproinsulin genes. AB - In rat there are two nonallelic insulins, I and II. We have cloned and sequenced double stranded cDNA copies of both preproinsulin mRNA I and II. Using the cloned sequence as probe, we established by the Southern blotting technique a restriction map of the two chromosomal genes. This map indicates that an intron exists within the insulin II gene. To examine this in more detail, we have isolated both genes from a library of rat DNA cloned in phage lambda. Restriction endonuclease analysis and direct DNA sequencing revealed that gene II contains two introns: a 490 base pair intron between the region encoding amino acids 38 and 39 of proinsulin, and a 119 base pair intron, which is 17 base pairs upstream from the initiation codon. Gene I is not interrupted within the protein coding region, but possesses an intron homologous to the 119 base pair intron of insulin II. We are studying the structure of insulin genes from other species to determine if the 490 base pair intron was lost or inserted in the duplicated gene. We have identified nuclear RNA molecules larger than preproinsulin mRNA which contain the transcribed intronic sequences. These molecules represent a new precursor in insulin biosynthesis. PMID- 6249168 TI - Presence of a pre-sequence (signal sequence) in the common precursor to ACTH and endorphin and the role of glycosylation in processing of the precursor and secretion of ACTH and endorphin. PMID- 6249169 TI - Biosynthetic studies on ACTH, beta-endorphin, and alpha-melanotropin in the rat. PMID- 6249170 TI - Detection and gene defects in the thalassemias and related disorders. PMID- 6249171 TI - Pathophysiology of thalassemia. AB - The clinical manifestations in homozygous thalassemia may be attributed to the defect in hemoglobin synthesis (Figure 16). It is best typified by beta thalassemia, where excess alpha chains accumulate to form intracytoplasmic erythrocytic inclusions. This leads to anemia, bone marrow hyperplasia, osteoporosis, hemosiderosis, and organ failure. PMID- 6249172 TI - Specific abnormalities of globin gene organization in the thalassemia syndromes. PMID- 6249173 TI - Dynamics of lipid motions in high-density lipoprotein subfractions HDL2 and HDL3: magnetic resonance studies. PMID- 6249175 TI - Lipid-protein interactions in enveloped viruses. PMID- 6249174 TI - The lipid-protein interface in biological membranes. AB - A significant fraction of the lipid in many biological membranes is at the lipid protein interface. The ESR and NMR data are in basic agreement that there is a dynamic equilibrium between lipid at the interface and the bulk bilayer. The lipid contact with the hydrophobic surfaces of the protein is spatially disordered compared to the bilayer lipids. The spatial disordering on the protein surface leads to the prediction that cooperative chain melting would not occur between lipid tails directly contacting the protein. This is in agreement with most, but not all of the DSC data. While there are some disagreements in the ESR studies, most of the quantitative data support the conclusion that the protein associated lipid is motionally restricted under physiologically relevant conditions. In general, the NMR data are in agreement that exchange between boundary and bilayer regions is rapid on the NMR time scale at physiological temperatures, although there are some differences in interpretation of the lipid dynamics. From the available data, several kinds of lipid binding sites may be involved. Most of these sites are probably nonspecific, but with some additional sites exhibiting specificity for the chemical properties of the polar head group. The relative binding constants can vary within the boundary layer with several exchange rates applying. Although most of the exchange rates are rapid, perhaps more rapid than specific mechanistic steps in the enzyme reaction, there is a characterizable set of thermodynamic parameters for the boundary and bilayer equilibrium. Although many of the lipid binding sites may have very low relative binding constants, they must be higher than the binding constants for nonspecific protein-protein contacts. One probable function of the boundary is to act as a molecular spacer, preventing indiscriminate protein-protein aggregation in the two-dimensional lipid solvent. Other roles are suggested by the higher relative binding constants of some specific lipids. PMID- 6249176 TI - Platelet structure and function role of prostaglandins. AB - A long way has been travelled since platelets were likened to sponges in 1961. At that time research on thrombotic mechanisms was mainly concentrated on blood coagulation. Since then, a shift of emphasis toward the study of platelets has dramatically evolved. How to prevent platelets from becoming sticky at sites of injury has been the main concern for platelet researchers over the past decade. Following adherence of platelets to a damaged vessel wall, prostaglandin synthesis is triggered leading to the formation of thromboxane A2, the most potent platelet activating agent so far discovered. By an "autocatalytic" process, thromboxane A2 together with the released ADP are responsible for the growth of the platelet thrombus. Among the substances released by the alpha granules is the mitogenic factor, which, by stimulating the proliferation of smooth muscle cells from the media to intimal layers in arteries, is instrumental in the generation of atherosclerotic plaques. The narrowing of the vessel wall lumen can be further aggravated by the formation of a thrombus over the plaque, thereby occluding the vessel, and leading to cardiovascular diseases or stroke depending on the location of the lesion. An all-out effort to find a means for preventing platelet stickiness is currently under way. The recent discovery of prostacyclin has been the cornerstone for most of the research carried out so far in this field. The presently available antiplatelet drugs should be used with caution. Indeed, whereas a dramatic thrombosis may occur with full platelet activation, a catastrophic hemorrhage may follow the "neutralization" of platelets. Eskimos who are fed with eicosapentaenoic acid, the precursor of a potent antiplatelet agent, may indeed be immune against thrombotic disorders; however, they have an increased tendency to bleed. PMID- 6249177 TI - Structure of erythrocyte membrane and its transport functions. AB - The red cell membrane contains approximately equal amounts of lipids and proteins. Membrane lipids are either phospholipids or neutral lipids, mostly unesterified cholesterol. Membrane phospholipids are asymmetrically arranged into a lipid bilayer two molecules thick. Choline phospholipids are more abundant in the extracellular surface whereas amino phospholipids are more concentrated on the inner leaflet of the bilayer. Cholesterol is intercalated between the phospholipid molecules. The relative amounts of cholesterol and phospholipids are responsible for the fluid properties of the erythrocyte membrane. Alterations in the membrane cholesterol-phospholipid ratio result in morphologically abnormal erythrocytes with decreased life span. Membrane proteins are also asymmetrically oriented within the lipid bilayer and can be divided into three functional sets: structural, catalytic and receptor proteins. Sprectrin and actin are the two main structural proteins that together form a submembranous cytoskeletal meshwork that is responsible for the viscoelastic properties of the erythrocyte membrane. Band 3, or the anion channel, is a major transmembranous protein involved in the transport of water and anions and is a carrier of the blood-group-I antigen. Glycophorin A, a sialic-acid-rich glycoprotein, is the major contact or receptor membrane polypeptide that also spans the lipid bilayer. The MN blood group determinants and possibly other biologic receptor sites have been localized on the extracellular portion of glycophorin A. At least 35 to 40 enzymes are confined to the membrane and, undoubtedly, play a vital role in the maintenance of normal structure and function of the erythrocyte. PMID- 6249178 TI - Evidence for the assignment of GUK 1 gene locus to 1q32 leads to q43 segment from gene dosage effect. AB - A male infant with dup (1) (q32 leads to q43) constitution is reported. He had mental and physical retardation and a constellation of dysmorphisms, which are considered characteristic of trisomics for the distal one-third of the long arm of chromosome 1. The assay for guanylate kinase 1 (GUK 1) activity showed a gene dosage effect and confirmed the regional assignment of this marker in the chromosomal region indicated by data derived from somatic hybrids. PMID- 6249179 TI - Genetical and biochemical studies on human phosphoserine phosphatase. AB - 1. Phosphoserine phosphatase (PSP), specific for D- and L-phosphoserine, has been identified in all human tissues. 2. PSP shows no activity towards phosphorylated serine residues in phosphoproteins. 3. In most tissues, PSP consists of a single major isozyme, probably determined by a single autosomal locus. 4. Other isozymes, identified quite frequently in such post-mortem tissues as kidney and liver, appear to be due to post-translational modification, the mode of which has not yet been identified. 5. Two different rare electrophoretic variants have been identified in 1% and 0.25% of 378 post-mortem kidneys (PSP 2-1 and PSP 3-1 respectively). 6. The three banded isozyme pattern of the rare variants suggests PSP is a dimeric enzyme. From gel filtration results the subunit molecular size is 26 000 daltons. 7. Homologous PSP isozymes have been detected in primates with similar electrophoretic mobility to that of the human enzyme. PMID- 6249180 TI - Expression of GALT in 9p chromosome alterations: assignment of GALT locus to 9cen leads to 9p22. AB - Determination of activity and electrophoretic mobility of GALT in patients with various chromosome 9 deletions and duplications confirms the assignment of its locus to 9p and suggests its locus is in the segment 9cen leads to p22. Two inversions of 9qh (inv(9)(p11q12)) did not alter GALT expression. PMID- 6249181 TI - Systemic candidiasis in mice. II.--Main role of polymorphonuclear leukocytes in resistance to infection. AB - Cyclophosphamide (CY) increased whereas the talc embedded in a calcium phosphate gel (TCP) decreased the susceptibility of mice to systemic candidiasis estimated by measuring mean survival time and "renal infectivity" 12 h after challenge. Transfers of plasma from CY- and TCP-treated mice did not modify cnadidiasis susceptibility of recipient mice. Granulopenia and granulocytosis induced respectively by CY and TCP were significantly correlated with susceptibility or resistance to candidiasis. Nevertheless, TCP produced significant reticuloendothelial stimulation which could be also correlated with TCP protection. Reticuloendothelial stimulation with associated granulopenia in TCP CY-treated mice gave protection against Listeria monocytogenes challenge but not against Candida albicans. Thus, blood polymorphonuclear leukocytes seem to play the main role in natural resistance of mice to candidiasis. This was corroborated after injection of immunostimulants; a good correlation was found between C. albicans resistance and the induced granulocytosis. PMID- 6249182 TI - Glycerol kinase deficiency with neuromuscular, skeletal, and adrenal abnormalities. AB - Two brothers with a recently described inborn error of metabolism characterized by glyceroluria, hyperglycerolemia, and generalized glycerol kinase deficiency had moderate psychomotor retardation, spasticity, growth failure, a nonspecific myopathy, osteoporosis, and adrenal insufficiency. Glycerol kinase activity in leukocytes and cultured fibroblasts was less than 5% of control values. Hepatic and renal tissue obtained at autopsy in one patient had similarly low enzyme activity. Thus the deficiency of glycerol kinase in these patients appears to be generalized and heritable, though the relationship of the clinical phenotype to the enzymatic defect is not yet established. PMID- 6249183 TI - Peripheral neuropathy in the cherry-red spot-myoclonus syndrome (sialidosis type I). PMID- 6249184 TI - The structure of proteins involved in active membrane transport. PMID- 6249185 TI - Magnetic circular dichroism of biological molecules. PMID- 6249186 TI - Certain slow synaptic responses: their properties and possible underlying mechanisms. PMID- 6249187 TI - Erythropoiesis. PMID- 6249188 TI - Active immunizations for adults. PMID- 6249189 TI - [Biosynthesis of the antibiotic, grizin, by prototrophic revertants of Streptomyces griseus biochemical mutants]. AB - Spontaneous and nitrosomethylbiuret-induced prototrophic revertants of various biochemical mutants of Str. griseus producing grisin, a streptothricin antibiotic, were isolated. The antibiotic production level of the revertants was studied. It was found that most of the prototrophic revertants synthesized much higher amounts of grisin than the initial biochemical mutants. It was also shown that a number of the prototrophic revertants of the methionine- and arginine dependent mutants synthesized 20-23% higher amounts of grisin as compared to the control. PMID- 6249190 TI - [Action of antibiotics on the growth and metabolic processes of streptomycetes and Nocardia]. AB - New experimental data on the effect of novobiocin, ristomycin and nystatin on growth and metabolism of Streptomycetes and Nocardia are presented. The study of the organisms producing other antibiotics showed that they were tens, hundreds and even thousands times more sensitive to the tested biologically active compounds than the organisms producing these compounds. The protein synthesis and antibiotic biosynthesis proved to be most sensitive out of the processes studied. The findings showed that during their evolution the antibiotic-producing organisms have developed definite protective mechanisms which enable them to resist relatively high concentrations of their own metabolites (antibiotics). This ensures them in their struggle for existence. PMID- 6249192 TI - CP-45,899 in combination with penicillin or ampicillin against penicillin resistant Staphylococcus, Haemophilus influenzae, and Bacteroides. AB - CP-45,899 is a new, semisynthetic beta-lactamase inhibitor. When tested alone, CP 45,899 displayed only weak antibacterial activity, with the notable exception of its potent action against penicillin-susceptible and -resistant Neisseria gonorrhoeae. A combination of 3.12 microgram of CP-45,899 per ml with 3.12 microgram of ampicillin per ml, tested in broth cultures, inhibited ca. 90% of resistant Staphylococcus and Haemophilus influenzae strains; similar data were obtained in a variety of media. The same combination of CP-45,899 with ampicillin or penicillin G inhibited 90% of Bacteroides fragilis as interpreted from agar dilution minimal inhibitory concentrations. Inhibitory concentrations of CP 45,899-ampicillin were bactericidal against H. influenzae strains and were as bactericidal as nafcillin or cephalothin against S. aureus. Ampicillin-resistant S. aureus, H. influenzae, and B. fragilis strains did not develop resistance to CP-45,899-ampicillin when transferred as many as six passages in the presence of a sublethal concentration of the combination. PMID- 6249191 TI - Combination chemotherapy: interaction of 5-methoxymethyldeoxyuridine with adenine arabinoside, 5-ethyldeoxyuridine, 5-iododeoxyuridine, and phosphonoacetic acid against herpes simplex virus types 1 and 2. AB - The antiviral activity of 5-methoxymethyl-2'-deoxyuridine (MMUdR) was compared with that of 5-iodo-2'-deoxyuridine (IUdR), 5-ethyl-2'-deoxyuridine (EtUdR), adenine arabinoside (Ara-A), and phosphonoacetic acid (PAA) against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). MMUdR was more potent than Ara-A and PAA but less active than EtUdR and IUdR against HSV-1 in rabbit kidney (RK 13) cells. In Vero cells, the antiviral activities of MMUdR, Ara-A, and PAA against HSV-1 were of the same order of magnitude. The antiviral potency against HSV-2 varied with the strain of virus used. All strains of HSV-2 were markedly inhibited by EtUdR and IUdR and to a lesser degree by PAA. However, considerable variation was noticed in the susceptibility of HSV-2 strains to Ara-A and MMUdR. Interaction of MMUdR with Ara-A, EtUdR, IUdR, and PAA was investigated by the method of response isobolograms. MMUdR showed synergistic activity in combination with Ara-A and PAA but antagonistic activity in combination with EtUdR and IUdR against herpesviruses. Minimum toxic dose (concentration required to produce definite evidence of microscopic cytotoxicity in rapidly growing RK-13 cells) was determined for each compound and was found to be 512, 172, 64, 8, and less than 0.5 microgram/ml for MMUdR, PAA, Ara-A, EtUdR, and IUdR, respectively. MMUdR was found to have the maximum antiviral index against HSV-1 (512) and HSV-2 strains X 265 (102) and ATCC (85). Antiviral index was defined as the minimum toxic dose divided by the dose that reduced plaque numbers by 50%. PMID- 6249193 TI - Effects of carbon sources on chemical composition of cell envelopes of Pseudomonas aeruginosa in association with polymyxin resistance. AB - Cells of Pseudomonas aeruginosa 015 were grown in basal medium with isobutyrate, DL-2-methylbutyrate, isovalerate, L-valine, L-isoleucine, L-leucine, D-glucose, or L-glutamate as the carbon source. Their resultant susceptibility to polymyxin B varied from a minimal inhibitory concentration of 2 U of polymyxin per ml for isobutyrate-grown cells to 975 U/ml for L-glutamate-grown cells. Cell envelopes from cells grown with each carbon source were compared with cell envelopes from cells grown in Mueller-Hinton broth as to their content of total protein, carbohydrate, and 2-keto-3-deoxyoctonate and as to their protein composition as determined by slab polyacrylamide gel electrophoresis. No pattern of cell envelope content of total protein, carbohydrate, 2-keto-3-deoxyoctonate, or outer membrane protein concentrations could be correlated with the degree of resistance to polymyxin. In these cells increased resistance to polymyxin was not associated with the loss of outer membrane proteins and lipopolysaccharide by the cell envelope. PMID- 6249194 TI - Identification of a nicotinamide adenine dinucleotide glycohydrolase and an associated inhibitor in isoniazid-susceptible and -resistant Mycobacterium phlei. AB - Nicotinamide adenine dinucleotide glycohydrolase (NADase) activity was demonstrated in the catalases fraction of Sephadex G-200-chromatographed sonic extracts of isoniazid (INH)-susceptible (Inhs) and -resistant (Inhr) Mycobacterium phlei. Since crude extracts had no demonstrable activity even after heating, active fractions of the NADase were purified chromatographically by removing the inhibitor with Sephadex G-200. Assays for oxidized nicotinamide adenine dinucleotide (NAD+) hydrolytic activity were done by following the disappearance of NAD+ by the methods of alcohol dehydrogenase or cyanide addition. The NADase activity was linear with respect to time as well as concentration of enzyme and was inhibited in the presence of 0.04 M NADP, benzoic acid hydrazide, or nicotinamide. Crude extracts or pooled concentrated Sephadex G 200 fractions eluting after the catalase inhibited NADase activity by at least 70%. Inhibitor activity was present in both the Inhs and Inhr strains of M. phlei. The activity of the partially purified inhibitors was reversible by INH or nicotinic acid hydrazide at levels between 10 and 100 mM. These findings indicate that an NADase inhibitor system which is sensitive to reversal by INH functions in both the Inhs and Inhr strains; however, unlike previous studies with other mycobacterial species, the enzyme is sensitive to inhibition by nicotinamide. Furthermore, the inhibitors are heat stable and sensitive to reversal by nicotinic acid hydrazide as well as INH. PMID- 6249195 TI - In vitro antimicrobial activity of cefoperazone, cefotaxime, moxalactam (LY127935), azlocillin, mezlocillin, and other beta-lactam antibiotics against Neisseria gonorrhoeae and Haemophilus influenzae, including beta-lactamase producing strains. AB - Minimum inhibitory concentrations and agar disk diffusion tests were determined on clinical isolates of beta-lactamase-positive and beta-lactamase-negative Neisseria gonorrhoeae and Haemophilus influenzae with the newer beta-lactam antibiotics, cefoperazone, cefotaxime, moxalactam (LY127935), azlocillin, mezlocillin, and piperacillin, and with seven older beta-lactam antibiotics. All the drugs were active against beta-lactamase-negative strains of N. gonorrhoeae and H. influenzae. The drug most active against beta-lactamase-positive N. gonorrhoeae was cefotaxime, followed closely by cefoperazone, moxalactam, piperacillin, and mezlocillin. The drugs most active against beta-lactamase positive strains of H. influenzae were cefotaxime, moxalactam, cefoperazone, and cefamandole. PMID- 6249196 TI - 2'-fluoro-5-iodo-aracytosine, a potent and selective anti-herpesvirus agent. AB - A newly synthesized pyrimidine analog, 2'-fluoro-5-iodo-aracytosine (FIAC), suppressed by 90% the replication of various strains of herpes simplex virus types 1 and 2 at concentrations of 0.0025 to 0.0126 microM. Cytotoxicity was minimal, as determined by trypan blue dye exclusion with norman Vero, WI-38, and NC-37 cell proliferation; the 50% inhibitory dose was 4 to 10 microM in a 4-day assay. When compared with other antiviral drugs, FIAC was active at much lower concentrations than arabinosylcytosine, iododeoxyuridine, and arabinosyladenine. It was slightly more active against herpes simplex virus type 1 than acycloquanosine and slightly more toxic to normal cells. FIAC was about 8,000 times more active against the replication of wild-type herpes simplex virus type 1 than against a mutant strain lacking the expression of virus-specified thymidine kinase. Since FIAC appears to be preferentially phosphorylated by the viral enzyme, this is probably responsible, at least in part, for the selectivity of its antiviral actions. Although FIAC appears to be an arabinosylcytosine analog, its antiviral activity was not reversed by deoxycytidine. The minimal cytotoxicity exhibited by FIAC for normal cells, however, was reversed by equimolar concentrations of deoxycytidine. Thymidine, which reversed the antiviral activity, was effective only when used in great excess. PMID- 6249197 TI - In vitro activities of miconazole, miconazole nitrate, and ketoconazole alone and combined with rifampin against Candida spp. and Torulopsis glabrata recovered from cancer patients. AB - A total of 440 fresh clinical isolates of yeasts from cancer patients were tested by an agar dilution technique against miconazole, miconazole nitrate, and ketoconazole individually and combined with 5 micrograms of rifampin per ml. Most strains of Candida albicans were susceptible to 0.5 microgram or less of the imidazoles per ml. Candida tropicalis required 2 to 4 micrograms of miconazole and its nitrate base per ml for inhibition and was resistant to ketoconazole. The 100% minimal inhibitory concentration of the imidazoles for Candida krusei was 1 microgram/ml. Susceptibility to 4 micrograms of miconazole and miconazole nitrate per ml occurred in 73 and 87% of Torulopsis glabrata strains, respectively, and none was susceptible to ketoconazole. Miconazole was most effective against the Candida spp., whereas its nitrate base was most active against T. glabrata. Synergy was observed when rifampin was combined with miconazole and miconazole nitrate but was not observed when rifampin was combined with ketoconazole. Synergy occurred most frequently when rifampin was combined with miconazole nitrate. PMID- 6249199 TI - The role of beta-lactamase and the outer-membrane structure in the resistance of Enterobacteriaceae to mecillinam. PMID- 6249198 TI - Comparison of moxalactam (LY127935) and cefotaxime against anaerobic bacteria. AB - The in vitro activities of moxalactam (LY127935 [6059S]) and cefotaxime were compared with those of cefoxitin, cefamandole, cefuroxime, carbenicillin, and penicillin by agar dilution susceptibility testing of a variety of anaerobic bacteria. Moxalactam proved to be the most active agent tested against Bacteroides fragilis and other species of the B. fragilis group. Moxalactam and cefotaxime showed activity similar to the other drugs against the remaining species of Bacteroides, Fusobacterium, Actinomyces, Propionibacterium, and Veillonella. Penicillin was the most effective drug tested against most species of Clostridium, the anaerobic gram-positive cocci, and Eubacterium lentum. PMID- 6249200 TI - Regulation of phosphoenolpyruvate carboxylase in C4 plants: inhibition by pyrophosphate of the enzyme from Amaranthus viridis. PMID- 6249201 TI - Properties of rabbit intestinal fructose 1,6-bisphosphatase. PMID- 6249202 TI - Differential inhibition of respiration and its dependent H+ extrusion by fluorescamine in rat liver mitochondria. PMID- 6249203 TI - Adenosine 3',5'-monophosphate-dependent protein kinase: interaction with guanidinium compounds. PMID- 6249204 TI - Evidence for a membrane-bound multienzyme sequence degrading cyclic adenosine 3':5'-monophosphate. PMID- 6249205 TI - Collagen synthesis in cultured osteoblast-like cells. PMID- 6249206 TI - Pituitary corticotropin-inhibiting peptide: properties and use in study of corticotropin action. PMID- 6249207 TI - The effect of cyclic AMP on glycoprotein secretion in isolated rat hepatocytes. PMID- 6249209 TI - Postnatal development of rat liver mitochondria: state 3 respiration, adenine nucleotide translocase activity, and the net accumulation of adenine nucleotides. PMID- 6249208 TI - Electron paramagnetic resonance properties and oxidation-reduction potentials of the molybdenum, flavin, and iron-sulfur centers of chicken liver xanthine dehydrogenase. PMID- 6249210 TI - Ion fluxes during T5 bacteriophage infection of Escherichia coli. PMID- 6249211 TI - Purification of human and monkey endonucleases acting on ultraviolet-irradiated DNA. PMID- 6249212 TI - Effect of ethanol on hepatic phosphatidate phosphohydrolase: dose-dependent enzyme induction and its abolition by adrenalectomy and pyrazole treatment. PMID- 6249213 TI - Inhibition and activation of fat cell adenylate cyclase by GTP is mediated by structures of different size. PMID- 6249214 TI - Effects of histidine modification on the biological and immunological activities of equine chorionic gonadotropin. PMID- 6249215 TI - Correlation of inhibition of fructose 1,6-bisphosphatase by AMP and the presence of the nucleotide-binding domain. PMID- 6249216 TI - Cyanide-resistant respiration in yeast. II. Characterization of a cyanide insensitive NAD(P)H oxidoreductase. PMID- 6249217 TI - Multiple forms of cyclic nucleotide phosphodiesterases in normal and goitrous rat thyroid. PMID- 6249218 TI - Cyclic AMP-dependent and -independent protein kinases in HeLa cells. PMID- 6249219 TI - Cu2+ probe of metal-ion binding sites in melanin using electron paramagnetic resonance spectroscopy. I. Synthetic melanins. PMID- 6249220 TI - Cu2+ probe of metal-ion binding sites in melanin using electron paramagentic resonance spectroscopy. II. Natural melanin. PMID- 6249221 TI - Latent and active forms of collagenase in rat uterine explant cultures: regulation of conversion by progestational steroids. PMID- 6249222 TI - Preferential response of thyroid glycosyltransferases to changes in thyrotropin stimulation. PMID- 6249223 TI - Plasma concentrations of vitamin D3 and its metabolites in the rat as influenced by vitamin D3 or 25-hydroxyvitamin D3 intakes. PMID- 6249224 TI - An in vitro study of the stability of the chicken intestinal cytosol 1,25 dihydroxyvitamin D3-specific receptor. PMID- 6249225 TI - Relationship between herbicide concentration and the rates of enzymatic degradation of 14C-diallate and 14C-triallate in soil. PMID- 6249226 TI - The chemotherapy of onchocerciasis V. A standard method for the determination of microfilarial density in skin snips. AB - The microfilarial density in 400 skin snips from 100 patients was determined using the standard technique of the Onchocerciasis Chemotherapeutic Research Centre (OCRC method), the method used by the Onchocerciasis Control Programme (OCP method), and also after collagenase digestion. The OCRC method was fairly consistent and detected 84% of the total microfilariae. The OCP method gave a density which was consistently 20% less than the OCRC method, indicating that the increase in weight in skin snips following incubation in saline was fairly predictable. It is concluded that collagenase digestion is not worthwhile as a routine technique in chemotherapeutic trials, for which the OCRC method is recommended. PMID- 6249227 TI - Infection with CDC group DF-2 gram-negative rod: report of two cases. AB - Two patients had bacteremia with Center for Disease Control group DF-2 Gram negative rods. Previously described patients infected with this organism had clinical syndromes including cellulitis, meningitis, and endocarditis, and generally were severely ill. One of our patients had acute oligoarticular arthritis. The other had fever, headache, malaise, and a generalized rash. In neither case was bacterial infection considered likely at onset, and neither patient received antibiotic therapy. Both patients recovered completely. The organism is a fastidious Gram-negative rod that only recently has been characterized. Methods for isolating and identifying the organism are reviewed. The spectrum and frequency of illnesses caused by this organism are probably greater than previously recognized. PMID- 6249228 TI - Monoarthritis with heterophil-negative infectious mononucleosis. Case of an older patient. AB - A patient aged 57 years with infectious mononucleosis and monoarthritis of the knee joint is described. To our knowledge, this association in elderly patients has not been reported heretofore, nor has the pathogenesis of arthritis in infectious mononucleosis been established. Because of the clinical picture and the synovial fluid findings, we suggest that the main mechanism of this arthritis is viral replication in the synovia. PMID- 6249229 TI - Nephrogenous cyclic AMP as a diagnostic test for hyperparathyroidism. PMID- 6249231 TI - [Kearns' syndrome: a case study (author's transl)]. AB - An anatomoclinical study of a case of Kearns' syndrome is reported. Neuro ophthalmic symptoms appeared when the child was 13 year-old. Two and a half years later occurred an episode of paroxystic atrioventricular block, after which the triad characterising the syndrome was completed: retinitis pigmentosa, ophthalmoplegia, disorder of heart conduction. The course was unfavorable despite pacemaker insertion. Study of the central nervous system showed spongiosis of the subcortical white substance, of the basal ganglia and of the cranial nerve nuclei. The specialized heart conduction tissue was the site of apparently primary degeneration. The extension of the visceral involvement is discussed in the light of published data. PMID- 6249230 TI - Regulatory properties of the ADPglucose pyrophosphorylase from Rhodopseudomonas sphaeroides and from Rhodopseudomonas gelatinosa. AB - The ADPglucose pyrophosphorylases from Rhodopseudomonas sphaeroides and Rhodopseudomonas gelatinosa are activated by fructose-6-phosphate, pyruvate and fructose-1,6 biophosphate-P2. The effects of the activators are to increase significantly the Vmax of ADPglucose synthesis and to lower the S0.5 values (concentration of substrates giving 50% maximal velocity) for ATP and MgCl2. The R. sphaeroides enzyme is inhibited by Pi while the R. gelatinosa enzyme is inhibited by AMP as well as by Pi. The interaction between inhibitor and activator is complex. At very low concentrations of activator the enzyme is more sensitized to inhibition. However, at higher concentrations of activator there is a decrease in the sensitivity of the enzyme towards inhibition. The findings are discussed with respect to glycogen synthesis in these microorganisms and may be related to findings that indicate that Rhodopseudomonads have the ability to degrade sugars via the Entner-Duodoroff or Embden-Meyerhoff pathways. PMID- 6249232 TI - Electron microscopy of Paneth cells in Crohn's disease. PMID- 6249233 TI - Intestinal development in insulinoma containing Psammoma bodies. Recapitulation of ultrastructural features. AB - Extensive junctional complex formation was observed between cells of an insulinoma with an acinar pattern. Cytolysosomes, multivesicular bodies, and small vesicles were present in the luminal aspect of acinar cells that were shedding cytoplasm. These and other ultrastructural features suggest a recapitulation of intestinal development by this tumor and this is consistent with an endodermal origin of pancreatic beta-cells or their precursors. Psammoma body formation, a rare occurrence in apudomas, was probably due to the accumulation of intraluminal cytoplasmic debris. PMID- 6249234 TI - Pancreatic islet cell damage. Its occurrence in neonatal coxsackievirus encephalomyocarditis. AB - Pancreata from five infants with culture-proven coxsackievirus encephalomyocarditis were studied for evidence of islet cell damage. Four of the five showed islet cell change, varying from clusters of cells with pyknotic nuclei to total islet necrosis. The lesion appeared to be characteristic of coxsackievirus and was not seen in the pancreata of neonates with other neonatal systemic viral infections. This confirms that coxsackievirus shows tropism for insular tissue and may play a role in the genesis of some cases of juvenile diabetes mellitus. Immunostaining was used to ascertain the specificity of the lesions. Damage to cells other than beta cells could be clearly demonstrated. The finding that all islet cell types may be involved lends support to the theory that juvenile diabetes mellitus may be a genetically determined failure to reconstitute the beta cells after viral injury. PMID- 6249235 TI - Exercise training in ischemic heart disease: effect on physical performance and plasma lipids, ACTH, and cortisol. PMID- 6249236 TI - Isolated sural neuropathy: report of two cases. AB - Two cases of isolated sural neuropathy are reported. In 1 case it was thought that the neuropathy was a direct result of compression of the sural nerve by a combat boot. In the 2nd case the etiology possibly involved 2 factors: chronic trauma to the nerve by walking on an inverted foot and irritative neuritis secondary to chronic, low-grade thrombophlebitis of the small saphenous vein. In both cases nonsurgical treatment was successful. Although isolated sural neuropathy occurs infrequently, the diagnosis should be considered in patients who have numbness along the lateral aspects of the foot. PMID- 6249237 TI - Effects of diethyldithiocarbamate and penicillamine on the tissue distribution of 63NiCl2 in mice. AB - The effects of sodium diethyldithiocarbamate and DL-penicillamine on the fate of 63Ni2+ in mice injected with 63NiCl2 were studied by whole body autoradiography and liquid scintillation counting. Sodium diethyldithiocarbamate caused a retention and redistribution of 63Ni2+ in the tissues. DL-penicillamine decreased the 63Ni2+-concentration in the tissues. The nickel-diethyldithiocarbamate complex is lipophilic, whereas the nickel-DL-penicillamine complex is hydrophilic, and these differences in chemical properties may determine the different effects which these chelating agents have on the fate of Ni2+. PMID- 6249238 TI - Inhibition of the hepatotoxicity of paracetamol and its irreversible binding to rat liver microsomal protein. AB - Dithiocarb and (+)-cyanidanol-3-prevented paracetamol-induced liver injury in rats in vivo. Both, as well as two other antihepatotoxic agents, deanol and DMSO, inhibited covalent binding of [3H]-paracetamol to rat liver microsomal proteins in vitro. Dithiocarb and (+)-cyanidanol-3 were the most effective inhibitors. The concentrations of the antidotes yielding 50% inhibition (I50) valued 1 . 8 x 10( 5) M for dithiocarb and 2 . 1 x 10(-5) M for (+)-cyanidanol-3. PMID- 6249239 TI - Dose-dependence of early cellular changes during liver carcinogenesis. PMID- 6249240 TI - Incidence of hepato-carcinoma in relation to aflatoxin intake. PMID- 6249242 TI - Persistence of high titre antibodies to the early antigens of cytomegalovirus in pregnant women. AB - Serial serum samples were obtained from 45 pregnant women who had been shown to possess complement fixing (CF) antibodies to cytomegalovirus (CMV) during a previous pregnancy. The serial samples were tested for antibodies against the early antigens (EA) and complement fixing antigens of CMV. All of the 45 women still possessed CF antibodies at the commencement of their next pregnancy. Six of the 45 women (13 per cent) lacked detectable IFA-EA antibodies whilst 19/45 (42 per cent) women possessed only low titres (less than or equal to 64) of these antibodies. However, 20/45 (44 per cent) women possessed high titre (greater than or equal to 128) antibodies despite having experienced their primary CMV infection many months previously. It is concluded that antibodies to the EA OF CMV are not as transitory as has been suggested and that their presence, even at high titre, in a serum sample from a pregnant woman cannot be taken as presumptive evidence of recent primary infection with this virus. PMID- 6249241 TI - Assessment of human cytomegalovirus antibody detection techniques. PMID- 6249243 TI - Prepubertal vaccination of mice against experimental infection of the genital tract with type 2 herpes simplex virus. AB - Pre-pubertal immunisation of mice with a formalin-inactivated type 1 and 2 herpes simplex virus vaccine conferred a level of life-long protection against primary type 2 genital infection. Protection levels were better with type 1 vaccine and strikingly influenced by vaccine dosage where a one-hundred-fold reduction from the standard vaccine dosage diminished protection to insignificant levels. Vaccine efficacy was not significantly affected by the method of virus inactivation, the number of immunisations or the age of the mouse at immunisation. Vaccination conferred better protection than previous type 2 genital infection; this may be a consequence of a higher antigenic dose, more acceptable antigenic presentation or to a perversion of the immune response in a latently infected animal to homologous virus challenge. PMID- 6249244 TI - Age and susceptibility of Swiss mice for mouse adenovirus, strain FL. AB - NMRI mice of different ages (24 hours, 10 to 12 days old, adults) were inoculated intraperitoneally with varying doses of mouse adenovirus. The susceptibility to disease was high in newborn mice (1 LD50 equalled 7 TCID50, as measured in mouse kidney cell cultures), medium in 10 days' old mice and almost nil in adult animals. The survival time was not greatly influenced by the virus dose. The susceptibility to infection is greatest in adults and lowest in 10 day old mice; these show a susceptibility equal to kidney cell cultures. In newborn mice, the virus spreads via the blood to all organs tested except for the intestinal tract, peak titers being reached in kidney and liver for at least 52 days, together with a sustained viruria. Adult mice could be infected by oral or intranasal installation. PMID- 6249245 TI - Physical integrity of herpes simplex virus following thermal inactivation. AB - The effect of thermal inactivation on the gross physical integrity of herpes simplex virus (HSV) was investigated. Purified preparations of HSV containing 3H thymidine were subjected to thermal inactivation at 36 degrees C, ph 6.3 and pH 7.8 and then were analysed by sucrose gradient centrifugation. The data indicated that although HSV inactivation at 36 degrees C was significantly greater at pH 7.8 than at 6.3, the gross physical integrity of most of the HSV in both of these inactivated virus populations was maintained. In addition, heat inactivated HSV adsorbed to mammalian cells as readily as non-inactivated HSV. Thus, thermal inactivation of HSV does not result in the physical disassembly of the virion particles or in the destruction of virus receptor activity. PMID- 6249246 TI - Cyclic nucleotides and platelet aggregation in hypertensive rats with ectopic pituitary tumor. AB - The transplantable pituitary tumor MtT-F4 secretes several pituitary hormones in Fisher rats, resulting in severe cardiovascular disease with a mineralocorticoid type of hypertension and hyperlipidemia. The mineralocorticoid-dependent hypertension possesses particular characteristics in humans and animals. It was of interest to study cyclic nucleotides and platelet aggregation in the Fisher rat with an MtT-F4 tumor in order to evaluate the type of abnormalities in this form of hypertension. The effect of administration of an anti-hyperlipidemic agent (clofibrate) was also evaluated. The animals bearing the tumor showed anomalies of platelet aggregation induced by the divalent cation ionophore A 23187, in that there was an apparent enhanced change in shape and a decreased rate of aggregation. Although the basal concentrations of cyclic nucleotides were normal, as were the increases in cyclic GMP induced by epinephrine, cyclic AMP concentrations increased less (about 2.7-fold) in response to PGE1 than in control Fisher rats (about 6-fold). A decreased stimulation of adenylate cyclase activity by PGE1 was observed in platelets of tumor-bearing rats. The administration of clofibrate to sham-operated animals somewhat lowered the increase of cyclic AMP in response to PGE1. In tumor-bearing animals, clofibrate considerably reduced plasma lipids, blood pressure and the degree of abnormalities in platelet aggregation and cyclic AMP in platelets. Thus, the abnormalities of platelet aggregation and regulation of cyclic nucleotides in the mineralocorticoid-type of hypertension induced by MtT-F4 were opposite to those found previously in spontaneous hypertension in rats. Hyperlipidemic and hypertensive rats with MtT-F4 tumor may provide a useful model for the study of the relatioship between hyperlipidemia and hypertension. PMID- 6249247 TI - [Morphologic and histochemical indices of hepatic function following bilateral subdiaphragmatic vagotomy]. AB - A complex morpho-functional investigation of the rat liver was performed after bilateral subdiaphragmal vagotomy by means of light, electron microscopy methods and a quantitative histochemical method. Some ultrastructural disorders in hepatocytes and in stellate reticuloendotheliocytes were revealed, with their maximal manifestation 7 days after vagotomy. At later stages (45 and 90 days), compensatory-restorative processes develop resulting in considerable (but not complete) normalization of the organ's structure. Quantitative histochemical investigations have demonstrated that even at the highest degree of the resulted disorders the liver preserves its ability to synthesize and accumulate glycogen, but the intensity of the process is considerably lowered. Functional changes are reversible in their character and correlate to the degree of structural disorders. PMID- 6249248 TI - [Submicroscopic changes in the mammary gland epithelium of white rats during chronic administration of high doses of estrogen]. AB - Ultrastructural alterations of female albino rat mammary glands in normal estrous cycle as well as in lactation, postlactation involution caused by weaning of sucklings from the nursing dams, and after administration of estrogen (synestrol) in a daily dose of 0.1 mg per 100 g body weight were studied. Particular attention was given to histochemical and morphometrical analys is of the secretory and vacuolar apparatus of the epithelial cells. A significant increase in the number of secretory granules in estrus as compared to that in diestrus accompanied by the reverse relationships in primary lysosome (small coated vesicles) count was observed. Similar relationships between the above parameters were found when the mammary glands of the lactating animals and those from the dams with their sucklings weaned were compared. The abundant primary and secondary lysosomes, autophagosomes, and heterophagosomes as well as some Golgi lamellae and smooth cisternae of endoplasmic reticulum filled with acid phosphatase were often observed in the epithelial cells of the involutary mammary glands, indicating the activation of the vacuolar apparatus. In synestrol-treated animals a gradual decrease in both secretory and catabolic activities occurred after transient successive increase of these two activities. The possible role of the relationship between the secretory and catabolic activities of the epithelial cells during mammary gland tumorogenesis is considered. PMID- 6249249 TI - [Certain varieties of malignant fibrous histiocytoma]. PMID- 6249250 TI - [Role of insulitis and autoimmune component in the etiology of diabetes mellitus]. PMID- 6249251 TI - Rate-limiting steps of the glycolytic pathway in the oral bacteria Streptococcus mutans and Streptococcus sanguis and the influence of acidic pH on the glucose metabolism. PMID- 6249252 TI - Aspects of the biochemistry, physiology and endocrinology of lactation. AB - Recent research on the endocrine control of the initiation of lactation, on the hypothalamic control of prolactin secretion, and on the utilization of nutrients by the mammary gland for the synthesis of milk is reviewed. Particular emphasis is placed on the mechanism of action of prolactin, and the role played by prolactin receptors. PMID- 6249253 TI - The chemistry of the collagen cross-links. Purification and characterization of cross-linked polymeric peptide material from mature collagen containing unknown amino acids. AB - A polymeric form of the alpha 1-chain C-terminal peptide alpha 1 CB6 (poly-alpha 1 CB6) was purified from CNBr digests of insoluble bovine tendon type-I-collagen by gel filtration and ion-exchage chromatography. The purified material had a molecular weight of 1.5 x 10(6)-5 x 10(6) on gel filtration and an amino acid content virtually identical with that of monomeric peptide alpha 1 CB6. The material could be adsorbed on affinity gels containing immobilized anti-(alpha 1 CB6-peptide non-helical region) antibodies and was an inhibitor of haemagglutination by the same antibodies of alpha 1 CB6-peptide-coated sheep erythrocytes. Periodate treatment of the material had no effect. Alkali hydrolysates were shown to contain two unknown amino acids, which were purified by gel filtration and ion-exchange chromatography in volatile buffers and are believed to be components of the mature cross-link of collagen. PMID- 6249254 TI - Electron-paramagnetic-resonance parameters of molybdenum(V) in sulphite oxidase from chicken liver. AB - A study has been made of e.p.r. signals due to Mo(V) in reduced sulphite oxidase (EC 1.8.3.1) from chicken liver. Reduction by SO3(2-), or photochemically in the presence of a deazaflavin derivative, produces spectra indistinguishable from one another. Three types of spectra from the enzyme were distingusihed and shown to correspond to single chemical species, since they could be simulated at both 9 and 35 GHz by using the same parameters. These were the low-pH form of the enzyme, with gav. 1.9805, the high-pH form, with gav. 1.9681 and a phosphate complex, with gav. 1.9741. The low-H form shows interaction with a single exchangeable proton, with A(1H)av. (hyperfine coupling constant) = 0.98 mT, probably in the form of an MoOH group. Parameters of the signals are compared with those for signals from xanthine oxidase and nitrate reductase. The signal from the phosphate complex of sulphite oxidase in unique among anion complexes of Mo-containing enzymes in showing no hyperfine coupling to protons. There is no evidence for additional weakly coupled protons or nitrogen nuclei in the sulphite oxidase signals. The possibility is considered that the enzymic mechanism involves abstraction of a proton and two electrons from HSO3- by a Mo = O group in the enzyme. PMID- 6249255 TI - 3-hydroxy-3-methylglutaryl-coenzyme A reductase A comparison of the modulation in vitro by phosphorylation and dephosphorylation to modulation of enzyme activity by feeding cholesterol- or cholestryamine-supplemented diets. AB - The activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (hydroxymethylglutaryl-CoA reductase) was considerably inhibited during incubation with ATP+Mg(2+). The inactivated enzyme was reactivated on further incubation with partially purified cytosolic phosphoprotein phosphatase. The inactivation was associated with a decrease in the apparent K(m) of the reductase for hydroxymethylglutaryl-CoA, and this was reversed on reactivation. The slight increase in activity observed during incubation of microsomal fraction without ATP was not associated with a change in apparent K(m) and, unlike the effect of the phosphatase, was not inhibited by NaF. Liver microsomal fraction from rats given cholesterol exhibited a low activity of hydroxymethylglutaryl-CoA reductase with a low apparent K(m) for hydroxymethylglutaryl-CoA. Microsomal fraction from rats fed cholestyramine exhibited a high activity with a high K(m). To discover whether these changes had resulted from phosphorylation and dephosphorylation of the reductase, microsomal fraction from rats fed the supplemented diets and the standard diet were inactivated with ATP and reactivated with phosphoprotein phosphatase. Inactivation reduced the maximal activity of the reductase in each microsomal preparation and also reduced the apparent K(m) for hydroxymethylglutaryl-CoA. There was no difference between the preparations in the degree of inactivation produced by ATP. Treatment with phosphatase restored both the maximal activity and the apparent K(m) of each preparation, but never significantly increased the activity above that observed with untreated microsomal fraction. It is concluded that hydroxymethylglutaryl-CoA reductase in microsomal fraction prepared by standard procedures is almost entirely in the dephosphorylated form, and that the difference in kinetic properties in untreated microsomal fraction from rats fed the three diets cannot be explained by differences in the degree of phosphorylation of the enzyme. PMID- 6249256 TI - Oxygen kinetics of frozen cytochrome oxidase. The capacity of the oxygen pocket. AB - Low-temperature kinetics of the reaction between O2 and cytochrome oxidase suggest the existence of an O2 pocket of limited capacity in membrane-bound cytochrome oxidase, and one of larger capacity in purified cytochrome oxidase. A model is proposed to explain the difference in capacity of the pockets. PMID- 6249257 TI - Actions of insulin and vitamin A on Sertoli cells. AB - The synthesis of androgen-binding protein by cultured Sertoli cells is increased by insulin, retinol, follitropin and testosterone. Only follitropin will stimulate an increase in cyclic AMP in these cells, yet each agent individually increased the synthesis of androgen-binding protein in short-term cultures. For long-term culture of Sertoli cells follitropin, testosterone, insulin, and retinol appeared to act synergistically to prolong the ability of the cells to secrete androgen-binding protein. These are the first reported results which suggest an action of insulin and retinol directly on Sertoli cells even though the importance of both factors in male reproduction is known. PMID- 6249258 TI - Guanosine 5'-triphosphate and guanosine 5'-[beta gamma-imido]triphosphate effect a collision coupling mechanism between the glucagon receptor and catalytic unit of adenylate cyclase. AB - 1. GTP, but not p[NH]ppG (guanosine 5'-[betagamma-imido]triphosphate), abolishes the sensitivity of glucagon-stimulated adenylate cyclase to the lipid-phase separations occurring in the outer half of the bilayer in liver plasma membranes from rat. 2. When either GTP or p[NH]ppG alone stimulate adenylate cyclase, the enzyme senses only those lipid-phase separations occurring in the inner half of the bilayer. 3. Trypsin treatment of intact hepatocytes has no effect on the basal, fluoride-, GTP- or p[NH]ppG-stimulated adenylate cyclase activity. However, (125)I-labelled-glucagon specific binding decays with a half-life matching that of the decay of glucagon-stimulated adenylate cyclase activity. 4. When GTP or p[NH]ppG are added to assays of glucagon-stimulated activity, the half-life of the trypsin-mediated decay of activity is substantially increased and the decay plots are no longer first-order. 5. Trypsin treatment of purified rat liver plasma membranes abolishes basal and all ligand-stimulated adenylate cyclase activity, and (125)I-labelled-glucagon specific binding. 6. Benzyl alcohol activates the GTP- and p[NH]ppG-stimulated activities in an identical fashion, whereas these activities are affected differently when glucagon is present in the assays. 7. We suggest that guanine nucleotides alter the mode of coupling between the receptor and catalytic unit. In the presence of glucagon and GTP, a complex of receptor, catalytic unit and nucleotide regulatory protein occurs as a transient intermediate, releasing a free unstable active catalytic unit. In the presence of p[NH]ppG and glucagon, the transient complex yields a relatively stable complex of the catalytic unit associated with a p[NH]ppG-bound nucleotide-regulatory protein. PMID- 6249259 TI - Low-level chemiluminescence of bovine heart submitochondrial particles. AB - Submitochondrial particles from bovine heart mitochondria showed low-level chemiluminescence when supplemented with organic hydroperoxides. Chemiluminescence seems to measure integratively radical reactions involved in lipid peroxidation and related processes. Maximal light-emission was about 1500 counts/s and was reached 2-10min after addition of hydroperoxides. Ethyl hydroperoxide, cumene hydroperoxide and t-butyl hydroperoxide were effective in that order. Antimycin and rotenone increased chemiluminescence by 50-60%; addition of substrates, NADH and succinate did not produce marked changes in the observed chemiluminescence. Cyanide inhibited chemiluminescence; half-maximal inhibitory effect was obtained with 0.03mm-cyanide and the inhibition was competitive with respect to t-butyl hydroperoxide. Externally added cytochrome c (10-20mum) had a marked stimulatory effect on chemiluminescence, namely a 12-fold increase in light-emission of antimycin-inhibited submitochondrial particles. Stimulation of hydroperoxide-induced chemiluminescence of submitochondrial particles by cytochrome c was matched by a burst of O(2) consumption. O(2) is believed to participate in the chain radical reactions that lead to lipid peroxidation. Superoxide anion seems to be involved in the chemiluminescence reactions as long as light-emission was 50-60% inhibitible by superoxide dismutase. Singlet-oxygen quenchers, e.g. beta-carotene and 1,4 diazabicyclo[2,2,2]-octane, affected light-emission. beta-Carotene was effective either when incorporated into the membranes or added to the cuvette. The present paper suggests that singlet molecular oxygen is mainly responsible for the light emission in the hydroperoxide-supplemented submitochondrial particles. PMID- 6249260 TI - Modulation of cyclic AMP-dependent protein kinase by vasopressin and calcitonin in cultured porcine renal LLC-PK1 cells. AB - We have previously demonstrated that a cultured porcine kidney cell, LLC-PK(1), maintains the characteristics of a polar renal epithelial cell in culture, and responds to salmon calcitonin and [arginine]vasopressin by increasing cyclic AMP content. To demonstrate the usefulness of this cell line as a model for the study of the biochemical events distal to cyclic AMP production, the activation of cyclic AMP-dependent protein kinase was examined. Intact cells in monolayer demonstrated progressive increases in cyclic AMP content and activation of protein kinase in response to [arginine]vasopressin (2-200nm) and salmon calcitonin (0.03-30nm) with both hormones fully activating the enzyme at a cell cyclic AMP content of 35pmol/mg of protein. Of the total cyclic AMP-dependent protein kinase activity, 80% was found in the 27000g supernatant fraction of sonicated cell material, and this soluble protein kinase could be fully activated by hormone. Conversely, the 27000g pellet contained a significant proportion of cyclic AMP-independent protein kinase and only 20% of total cell cyclic AMP dependent protein kinase; the latter showed little response to hormone. On the basis of DEAE-cellulose chromatography, type II protein kinase was the predominant isoenzyme in both soluble and particulate fractions of the LLC-PK(1) cells and the soluble fractions of rat and guinea-pig renal medulla. Thus, the LLC-PK(1) cell line can serve as a model for hormonal modulation of protein kinase and as a potential source for defining the endogenous substrates for these enzymes. PMID- 6249261 TI - Effect of insulin, catecholamines and calcium ions on phospholipid metabolism in isolated white fat-cells. AB - The incorporation of [(32)P]P(i) into phosphatidylinositol by rat fat-cells was markedly increased in the presence of adrenaline. Phosphatidic acid labelling was also increased, but to a lesser extent. These effects are due to alpha(1) adrenergic stimulation since they were unaffected by propranolol, blocked by alpha-blockers in the potency order prazosin< poly(C). Divalent cations (Mg2+ or Mn2+) was required for the enzymatic activity, but monovalent cations (Na+, K+ or NH4+) inhibited the enzyme. The breakdown of poly(C) and poly(U) by the enzyme was inhibited by spermine, but that of poly(A) was not influenced by spermine. The enzyme was inhibited by p-chloromercuribenzoate and poly(G), but not by rat-liver ribonuclease-inhibitor and anti-RNase A serum. PMID- 6249373 TI - Protection of transfective poliovirion RNA by histidine. AB - Transfectivity titers of RNA preparations obtained from purified poliovirions in phosphate-buffered saline using phenol were low. Addition of tissue culture nutrient medium to the virions prior to extractin with phenol increased the RNA titers 100-1000-fold. The 32 solute differences between the phosphate-buffered saline and the nutrient medium were divided into three blocs for testing. Only the bloc containing the 13 amino acids of the nutrient medium enabled the preparation of high-titer RNA. Tests of the individuals amino acids revealed that L-histidine has high activity, L-cystine and L-glutamine moderate activity, and the remaining ten zero or very slight activity. Five congeners of L-histidine, viz. D-histidine, histamine, L-histidine methyl ester, alpha-N-acetyl-L histidine, and L-histidyl-glycine, also had high activity; but imidazole had no activity. The histidine effect was obtained whether transfection was enhanced by DEAE-dextran or by bentonite. Histidine was fully effective only when it was added to the virions before or very shortly after the phenol; later additions of histidine were progressively less effective. Without added histidine, RNA preparations made very rapidly and inoculated promptly showed high transfectivity titers, but the transfectivity was highly labile; with histidine present, the high RNA titers were stable. Histidine did not reactivate the inactivated RNA. PMID- 6249374 TI - Regulation of ornithine decarboxylase activity by amino acids, cyclic AMP and luteinizing hormone in cultured mammalian cells. AB - Any one of five amino acis (alanine, asparagine, glutamine, glycine, and serine) is an essential requirement for the induction of ornithine decarboxylase (EC 4.1.1.17) in cultured chinese hamster ovary (CHO) cells maintained with a salts/glucose, medium. Each of these amino acids induced a striking activation of ornithine decarboxylase in the presence of dibutyryl cyclic AMP and luteinizing hormone. The effect of the other amino acids was considerably less or negligible. The active amino acids at optimal concentrations (10 mM) induced only a 10-20 fold enhancement of enzyme activity alone, while in the presence of dibutyryl cyclic AMP, ornithine decarboxylase activity was increased 40-50 fold within 7-8 h. Of the hormones and drugs tested, luteinizing hormone resulted in the highest (300-500 fold) induction of ornithine decarboxylase with optimal concentrations of dibutyryl cyclic AMP and asparagnine. Omission of dibutyryl cyclic AMP reduced this maximal activation to one half while optimal levels of luteinizing hormone alone caused no enhancement of ornithine decarboxylase activity. The induction of ornithine decarboxylase elicited by dibutyryl cyclic AMP, amino acid and luteinizing hormone was diminished about 50% with inhibitors of RNA and protein synthesis. The specific amino acid requirements for ornithine decarboxylase induction in chinese hamster ovary cells was similar to the requirements for induction in two other transformed cell lines. Understanding the mechanism of enzyme induction requires an identification of the essential components of the regulatory system. The essential requirement for enzyme induction is one of five amino acids. The induction of ornithine decarboxylase by dibutyryl cyclic AMP and luteinizing hormone was additive in the presence of an active amino acid. PMID- 6249375 TI - Purification and properties of two ribonucleases and a nuclease from barley seeds. AB - Three enzymes possessing RNAase activity were isolated from barley seeds. These enzymes were further purified by ammonium sulphate precipitation DEAE-cellulose chromatography, gel filtration on Sephadex G-75 and DEAE-Sephadex A-50 chromatography. These enzymes have been characterized and classified as: 1. Plant RNAase I (EC 3.1.27.1). It has a pH optimum at 5.7 and molecular weight of 19 000. 2. Plant RNAase II (EC 3.1.27.1). It has a pH optimum at 6.35 and molecular weight of 19 000. 3. Plant nuclease I (EC 3.1.30.2). It has a pH optimum at 6.8 and molecular weight of 37 000. Two RNAases were purified to homogeneity by means of affinity chromatography on poly(G)-Sepharose 4B, as shown by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. PMID- 6249376 TI - Chromatin-associated protein kinases specific for acidic proteins. AB - Protein kinases (EC 2.7.1.37) were eluted by 0.4 NaCl from chromatin of several mammalian cell typs. The enzymes were partially purified by ion-exchange chromatography, DNA-cellulose columns and sucrose gradient centrifugation. At least five different enzymes could be distinguished by their biochemical properties and their substrate specificities. Three of the enzyme activities tested phosphorylate different sets of histones, while two enzymes phosphorylate acidic nonhistone chromatin proteins or artificial substrates like casein and phosvitin. The two nonhistone protein kinases have slightly different pH and salt optima. They sediment through sucrose gradients with approx. 4 S and approx. 8 S, respectively. These enzymes are further characterized by their different substrate specificity, since they phosphorylate different, though partially overlapping sets of nonhistone chromatin proteins. Enzymes with these properties were deteced in chromatin from mouse ascites cells, bovine lymphocytes, African green monkey kidney cells and a human SV40 transformed cell line. PMID- 6249377 TI - Transformations of 5,8,11,14,17-eicosapentaenoic acid in human platelets. AB - 5,8,11,14,17-[1-14C]Eicosapentaenoic acid was prepared biosynthetically from [1 14C]arachidonic acid using the fungus, Saprolegnia parasitica. Incubation of 5,8,11,14,17-[1-14C]eicosapentaenoic acid with suspensions of human platelets led to the formation of three labeled compounds which were identified as thromboxane B3 (2-5% yield), 12-hydroxy-5,8,10,14-heptadecatetraenoic acid (2-5% yield), and 12-hydroxy-5,8,10,14,17-eicosapentaenoic acid (7-59% yield). PMID- 6249379 TI - Electron spin resonance study of human transcortin: Thiol groups and binding site topography. AB - A series of cortisol analogs bearing a nitroxide free radical on C-17 side chains with a variation of distance between the steroid D-ring and the spin label from 7.4 to 17.6 A has been synthesized. These analogs were found to retain a good affinity for the specific corticosteroid binding site of purified human transcortin. The spin-labeled cortisol analogs were used to probe the human transcortin binding site structure by electron spin resonance (ESR) spectroscopy. A total depth of approx. 25 A was estimated for the binding site crevice. Use of sulfhydryl reagents (N-ethylmaleimide, p-chloromercuribenzoate) showed that a maximum of two sulfhydryl groups were titratable after reduction and denaturation of the protein. One of these thiol groups appeared to be involved in the cortisol binding site and could not be detected in the presence of bound steroid. ESR study of its environment, using spin-labeled N-ethylmaleimide reagents of various side-chain lengths, led to the conclusion that this thiol was at a depth of approx. 15 A or more in the binding site cavity. The second sulfhydryl group may be present in an oxidized form in the purified native transcortin, since it became titratable only after reductive treatment of the protein. ESR study showed that this thiol may be located in a crevice at approx. 15 A from the protein surface. These findings are compatible with a structural organization of the transcortin cortisol binding site, taking into account tentative models previously proposed by others. PMID- 6249378 TI - Prostaglandin I2 synthesis and elevation of cyclic AMP levels in 3T3 fibroblasts. AB - Arachidonic acid and prostaglandin H2 elevate the levels of adenosine 3':5' monophosphate (cyclic AMP) in Balb/c 3T3 fibroblasts. This effect was inhibited by 15-hydroperoxy-5,8,11,13-eicosatetraenoic acid, an inhibitor of prostaglandin I2 synthase (Claesson, H.-E., Lindgren, J.A. and Hammarstr!om, S. (1977) FEBS Lett. 81, 415-418). After addition of arachidonic acid to 3T3 cultures, cellular cyclic AMP levels and growth medium concentrations of 6-ketoprostaglandin F1 alpha (degradation product of prostaglandin I2) were quantitatively determined. The stimulatory effect of exogenously-added prostaglandin I2 on cellular cyclic AMP levels was also determined. The results indicate that the endogenous production of prostaglandin I2 is sufficient to explain the stimulatory action of arachidonic acid on cyclic AMP formation in 3T3 fibroblasts. PMID- 6249380 TI - Functional properties of the glycosylated minor hemoglobins A1a-1,A1a-2 and A1b. EPR evidence for increased stability of the low affinity quaternary structure and decreased susceptibility to organic phosphate. AB - Electron paramagnetic resonance (EPR) spectra of the glycosylated minor hemoglobins A1a-1, A1a-2, A1b and A1c and the major hemoglobin A0 in the nitrosyl form have been obtained in the absence and presence of inositol hexaphosphate. In the absence of inositol hexaphosphate, nitrosyl hemoglobins A1a-1, A1a-2 and A1b exhibited a triplet hyperfine structure centered at g = 2.009 which has been shown to be diagnostic of the low affinity (T) quaternary structure. Addition of inositol hexaphosphate to nitrosyl hemoglobins A0, A1c, A1b and A1a-2 developed a triplet hyperfine structure of the EPR spectra but the magnitude of the hyperfine was decreased in the order of hemoglobins A0, A1c, A1b and A1a-2. However, inositol hexaphosphate had essentially no effect on the EPR spectrum of nitrosyl hemoglobin A1a-1. The present results account qualitatively for the oxygen binding properties of these glycosylated minor hemoglobins in the framework of a two-state allosteric model. PMID- 6249381 TI - Semi-synthetic analogs of cytochrome c. Substitutions for methionine at position 80. AB - Derivatives of cytochrome c having S-methyl cysteine and ethionine substituted for methionine residue 80 have been synthesized in order to study the effects of structural perturbations near the heme on the biological function of cytochrome c. The etionine derivative has 96% as much activity as native cytochrome c in the succinate oxidase system, whereas the S-methyl cysteine analog is totally inactive. PMID- 6249382 TI - Differential solubilization of nuclear glucocorticoid receptors by DNAase I and DNAase II. AB - This study analyzes the sensitivity of nuclear bound glucocorticoid receptors to solubilization from nuclei by DNAase I and DNAase II. Thymocytes were incubated with 10(-8) M [3H]dexamethasone, [3H]cortisol or [3H]triamcinolone acetonide, without or with 10(-6) M unlabelled dexamethasone, for 30 min at 37 degrees C and nuclei from these cells were digested with either DNAase I and DNAase II. DNAase I for 2 h at 3 degrees C leads to solubilization of 60% of the nuclear DNA and release of 10--20% triamcinolone acetonide-receptor, 30--40% dexamethasone receptor and 85--90% cortisol-receptor. DNAase II at the same enzymatic concentration solubilizes only 10--20% of the nuclear DNA, but releases 40--50% triamcinolone-receptor, 60--70% dexamethasone-receptor and 100% cortisol receptor. Release of nuclear bound dexamethasone-receptor by DNAase I parallels the solubilization of DNA, reaching maximum values by 2 h at 3 degrees C, whereas maximal release by DNAase II is obtained within 45 min when DNA solubilization is not complete. When nuclei initially extracted with DNAase I are re-extracted with DNAase II, greater than 65% of the DNAase I residual dexamethasone-receptors are solubilized, whereas DNAase I is ineffective in solubilizing DNAase II residual dexamethasone-receptors. DNAase I solubilizes only 30% of the 0.4 M KCl residual dexamethasone-receptor whereas DNAase II digests over 90% of this fraction. DNAase I extracts of nuclear dexamethasone-receptor chromatograph on G-100 Sephadex as a single radioactive peak just after the void volume, whereas DNAase II extracts of nuclear dexamethasone-receptor chromatograph as two peaks of radioactivity, one which is similar to the DNAase I solubilized receptor and a second broad peak of macromolecular bound radioactivity which is smaller in size. PMID- 6249383 TI - Developmental changes of two distinct ribonuclease H activities from rat brain and characterization of these enzymes. AB - The specific activities of both Mg2+- and Mn2+-dependent ribonucleases H (RNAase H) from rat cerebella increased up to approx. the 6th day after birth and then decreased in adult rats. Those isolated from the non-cerebellar part decreased gradually toward adult levels after birth. The two enzymes could be separated by phosphocellulose chromatography. They can be distinguished from one another by their ionic requirement, molecular weight, sedimentation coefficient, optimal pH, sensitivity to the -SH reagent, and the effects of salt, polyamine and pyrophosphate. Both enzymes liberate a mixture of oligonucleotides from RAN substrates, with 5'-phosphate and 3'-hydroxyl termini. PMID- 6249384 TI - Control mechanisms in the acceleration of hepatic glycogen degradation during hypoxia. AB - Hepatic glycogen metabolism in aerobic and hypoxic conditions has been assessed with respect to glycogenolysis, phosphorylase alpha activity and nucleotide content. Insulin did not inhibit glycogen breakdown nor stimulate lipogenesis in the aerobic perfused liver. Partial ischaemia induced glycogen breakdown, release of glucose and changes in nucleotide content in the perfused liver. Phosphorylase alpha content increased within 2 min in response to total ischaemia, in vivo and in the perfused liver. This change was paralleled by an increase in hepatic AMP. Glycogen synthase alpha activity decreased, as did the hepatic content of both cyclic AMP and cyclic GMP. PMID- 6249385 TI - Evidence for a cyclic AMP system highly sensitive to secretin in gastric glands isolated from the rat fundus and antrum. AB - The effects of secretin and vasointestinal peptide (VIP) on the production of cyclic AMP have been studied in gastric glands isolated by means of EDTA from rat fundic and antral mucosa. (1) In gastric fundus, secretin and VIP caused a time- and temperature-dependent stimulation of cyclic AMP production that was maximal when the test agents were incubated for 60 min at 20 degrees C in the presence of 0.5 mM 3-isobutyl-1-methylxanthine as a phosphodiesterase inhibitor. The dose response curve was monophasic for both peptides, the production of cyclic AMP being sensitive to 10(-10) M secretin and to 5 . 10(-8) M VIP. Half-maximal stimulation was obtained with 2.9 10(-9) M secretin or 2 . 10(-7) M VIP and the maximal stimulation represented a 21-fold and a 19-fold increase above control for secretin and VIP, respectively. Histamine also stimulated cyclic AMP production, with a Km of about 5 . 10(-4) M. No additive effect on cyclic AMP production was oberved when secretin and VIP were simultaneously added at maximally active concentrations, while an additive effect was observed when secretin and histamine were added together. (2) In gastric antrum, the characteristics of the secretin- and VIP-stimulated cyclic AMP production were similar to those observed in gastric fundus. Histamine nevertheless failed to stimulate the formation of cyclic AMP in antral mucosa. (3) These data demonstrate the existence of a cyclic AMP system highly sensitive to secretin in gastric glands isolated from the rat fundus and antrum and suggest that VIP operates through this system. (4) It is proposed that the pepsinogen- and/or mucous-secreting cells are implicated in the regulation of cyclic AMP production by secretin in gastric glands of the rat. PMID- 6249386 TI - Activation of type I and type II cyclic AMP-dependent protein kinases by 2,8 disubstituted derivatives of cyclic AMP. AB - Derivatives of cyclic AMP with substituents in both the 2-position (methyl or butyl) and the 8-position (bromo, benzylthio, p-chlorophenylthio or azido) and their singly modified parent compounds were examined for their abilities to activate type I isozymes of cyclic AMP-dependent protein kinases from rabbit and porcine muscle and type II isozymes of cyclic AMP-dependent protein kinases from bovine brain and heart. The specificity of 2-n-butyl-cyclic AMP for type II was substantially reduced or eliminated by the addition of 8-substituents. The lack of specificity of 2-methyl-cyclic AMP for either type I or II was not changed by the addition of 8-substituents. PMID- 6249387 TI - Rat pancreas adenylate cyclase: VII. Effect of extracellular calcium on pancreozymin-induced cyclic AMP formation. AB - 1. The effect of stimulation of adenylate cyclase by pancreozymin-C-octapeptide on the cyclic AMP level of rat pancreatic fragments has been investigated. 2. In normal Krebs-Ringer bicarbonate medium pancreozymin-C-octapeptide causes a slight increase in pancreatic cyclic AMP level; this increase can be considerably enhanced by incubation in a calcium-free incubation medium. 3. The dose-response curve for pancreozymin-C-octapeptide in calcium-free medium is shifted to lower peptide concentrations, compared to the curve in normal Krebs-Ringer bicarbonate medium. 4. The maximal stimulatory effect of pancreozymin-C-octapeptide is obtained at a 1-methyl-3-isobutylxanthine concentration of 10 mM. 5. It suffices to lower the Ca2+-concentration of the medium from 2.5 to 1.5 mM to get the maximal increase in cyclic AMP content under influence of pancreozymin-C octapeptide. 6. It is concluded that extracellular calcium antagonizes the stimulation of adenylate cyclase by pancreozymin-C-octapeptide. This suggests that a low cytoplasmic Ca2+-concentration is required for the maximal response of acinar cell adenylate cyclase to pancreozymin. PMID- 6249388 TI - Calcium-dependent proteins in platelets: response of calcium-activated protease in normal and thrombasthenic platelets to aggregating agents. PMID- 6249389 TI - Characteristics of a new binding protein distinct from the kinase for guanosine 3':5'-monophosphate in rat platelets. AB - A new type of cyclic GMP binding protein was recently identified in our laboratory (Hamet, P. and Coquil, J.-F. (1978) J. Cyclic Nucleotide Res. 4, 281- 290). The binding, recovered in the supernatant fractions, is highly specific for cyclic GMP and is clearly distinct from the binding to cyclic GMP-dependent protein kinase. Chromatography on DEAE-Sepharose separated the cyclic GMP binding protein from cyclic AMP binding, cyclic AMP-dependent kinase activities, and from guanylate cyclase. The optimal binding occurs at high pH and in the presence of thiol reagents. Several phosphodiesterase inhibitors increase the affinity of binding (Kd was 353 +/- 60 nM in the absence and 13.4 +/- 1.5 nM in the presence of 1-methyl-3-isobutyl-xanthine). The molecular weight of the binding protein was determined to be about 176,000 and the sedimentation coefficient was 6.4 S. While the binding and phosphodiesterase activities co-migrated on DEAE-Sepharose, gel filtration and sucrose gradients, certain treatments (such as increasing the concentrations of salt and heating) were able to influence one activity while having no effect on the other. Hence, the binding activity may be involved in the regulation of the activity of cyclic GMP phosphodiesterase. Since the binding protein appears to be the only 'receptor' for cyclic GMP detectable in platelets, this protein and/or its relation to cyclic GMP phosphodiesterase may play a role in the mechanism of action of cyclic GMP in platelets. PMID- 6249390 TI - Site of synthesis of geranylgeraniol derivatives in intact spinach chloroplasts. AB - Chloroplasts isolated from fully developed spinach leaves and incubated in the presence of isopentenyl pyrophosphate were able to synthesize rapidly geranylgeranyl chlorophyll alpha and geranylgeraniol. The biosynthesis of the geranylgeraniol derivatives from isopentenyl pyrophosphate is a compartimentalized process. The membrane fractions (thylakoid and envelope membranes) were essentially unable to synthesize geranylgeraniol, geranylgeranyl pyrophosphate and geranylgeranyl chlorophyll alpha. When stromal and thylakoid fractions were combined the capacity to synthesize geranylgeranyl chlorophyll alpha and geranylgeraniol was restored. When stromal and envelope membrane fractions were combined the capacity to synthesize gernylgeranyl pyrophosphate and geranylgeraniol was restored. The products of the reaction were discharged inside the lipid phase of the membranes. PMID- 6249391 TI - Formation of cyclic AMP from exogenous ATP by isolated hepatocytes and adipocytes. AB - Suspensions of isolated rat hepatocytes and adipocytes converted exogenous ATP to cyclic AMP at a rate which was about 30--50% of that observed with homogenates of isolated cells. Formation of cyclic AMP was stimulated by hormones (isoprenaline in the case of adipose tissue and glucagon in the case of liver) and sodium fluoride. Experiments with [alpha-32P]ATP indicated that the conversion of exogenous ATP to cyclic AMP did not occur within the cells. It is proposed that in isolated hepatocytes ad adipocytes some catalytic units of adenylate cyclase are exposed on the outer surface of the cell membrane. PMID- 6249392 TI - Preparation and properties of glucagon analogs prepared by semi-synthesis from CNBr-glucagon. AB - The semi-synthetic approach has been used to obtain new analogs of the peptide hormone glucagon. Using the highly purified 27 amino acid fragment of cyanogen bromide-treated glucagon, we have prepared, by nucleophilic addition to the lactone ring, the following derivatives: CNBr-Gly28-glucagon, CNBr-glucagon hydrazide, CNBr-glucagon n-butylamide and CNBr-glucagon biotinamide. Direct aminolysis of the lactone was successful only with sterically unhindered primary amines. Addition of an amino acid could be accomplished by formation of the peptide hydrazide followed by azide coupling. All these analogs were full agonists with decreased potency relative to the native hormone. Examination of the structure-function relationships of these new C-terminal glucagon derivatives suggests that the hydrophobic side-chain of methionine is important to the binding of glucagon to its receptor and that the C-terminal portion of glucagon is only involved in the binding of the hormone to the receptor and not in the transduction process. PMID- 6249393 TI - Phosphorylation and dephosphorylation of the regulatory subunit of cyclic 3',5' monophosphate-dependent protein kinase (type II) in vivo and in vitro. AB - A phosphorylated regulatory subunit of cyclic AMP-dependent protein kinase (type II) was purified to homogeneity from inorganic [32P]phosphate-injected rats. A new method of measuring the phosphorylation reaction was developed. It was found that this regulatory subunit was phosphorylated in cells and comprised 60, 82 and 55% of the total regulatory subunit in brain, heart and liver cytosol fractions from rats, respectively. Dephosphorylation was stimuated by cyclic nucleotides. The Ka values for cyclic AMP and cyclic IMP were 0.30 and 1.0 microM, respectively. Purified phosphoprotein phosphatase could dephosphorylate the regulatory subunit and this reaction was also stimulated by cyclic nucleotides with similar Ka values. The inhibitors of phosphoprotein phosphatase, NaF and ZnCl2, protected against dephosphorylation unless ADP or cyclic AMP were present. PMID- 6249394 TI - Detection of a calmodulin-sensitive cyclic nucleotide phosphodiesterase in rat parotid gland. AB - Calmodulin coupled to Sepharose has provided a rapid and sensitive means of isolating a cyclic nucleotide phosphodiesterase activity which is stimulated by the calmodulin-Ca2+ complex, from rat parotid gland. Initial experiments established that phosphodiesterase activity sensitive to calmodulin and Ca2+ could not be demonstrated in crude extracts of rat parotid gland or after partial purification of rat parotid phosphodiesterase over DEAE-cellulose. However, it was possible to readily demonstrate the presence of a cyclic nucleotide phosphodiesterase activity regulated by calmodulin if the extracts were first purified by batch ion-exchange chromatography over DEAE-cellulose followed by affinity chromatography with calmodulin coupled to Sepharose. The batch ion exchange chromatography step removed the major portion of free parotid calmodulin which could compete with calmodulin-coupled Sepharose for the proteins regulated by calmodulin. Thus, by employing an initial chromatography step over DEAE cellulose to separate phosphodiesterase activity from calmodulin, it was possible to increase the recovery of calmodulin-sensitive phosphodiesterase after affinity chromatrography with calmodulin coupled to Sepharose. This approach should be useful for demonstrating the presence of and for purifying other parotid proteins regulated by calmodulin. PMID- 6249395 TI - Properties of solubilized and purified follitropin receptor from calf testis. PMID- 6249396 TI - [Stoichiometric conditions for reactions between molecules of certain biogenic amines and their analogs and receptors]. PMID- 6249397 TI - [Photoinduced calcium ion transport through photoreceptor membranes]. PMID- 6249399 TI - [Effect of deuterization and possible water molecule participation in cytochrome c oxidation]. PMID- 6249398 TI - [Paramagnetic centers during carcinognesis induced by an RNA-containing virus]. AB - An ESR method was used to investigate the metalloenzyme centres, characteristics of cell energetic and detoxicity systems of models of tumors induced by RNA virus MSV(M) as progressor and regressor of tumor development. Different stages of ESR signal formation and its reverse transformation centres that reflect relations between tumor and organism the iron--sulphur proteins proved to be the most important. PMID- 6249400 TI - [Chemical composition of calcium channels of characean algal cells]. AB - The present study was performed to determine the chemical composition and molecular weight of channel-forming complex by fractioning the cell homogenate supernatant by different means (chromatography, gel-electrophoresis, using dissociating and denaturating agents). Availability of the channel-forming complexes in individual fractions is judged from reconstruction of channels in BLM. The Ca-channels reconstructed in BLM are formed by molecules of a protein nature (presumably, peptides). Their molecular weight is no more than 20000 (presumably, 5000). A high stability of spacial organization of channel forming molecules was observed. The channels--subunits aggregate without any change in properties of the selective filter. The thermodynamically preferred agagregates have conductivity of 200 pmho in 0.1 M KCl and seem to consist of 80 channels- subunits which are switched off and on all together. PMID- 6249401 TI - [Lipid layer distortion as a possible cause of active ion transport through biological membranes]. PMID- 6249402 TI - [Paramagnetic centers in regenerating mouse liver]. PMID- 6249403 TI - [Protonation of acridine in a hydrated protein matrix]. AB - Fluorescence of polycrystaline acridine in the matrix of solid alpha-chymotrypsin was studied at different humidities of the atmosphere. The fluorescence was not changed when the mixture was extensively dried. At intermediate and high humidities two consecutive processes proceed: 1) the solid-state dissolution of acridine crystals in the protein matrix and 2) the capture of protons by dispersed acridine molecules due to the proton transport through H-bound chains of water molecules from the protein proton-donor groups. PMID- 6249404 TI - Identification of endogenous and exogenous activity in a molluscan neurone by spike train analysis. AB - The statistical properties of background spike train activity recorded from a molluscan neurone are used to identify lengths of discharge which are produced by endogeneous pacemaker mechanisms. Such pacemaker discharge has an infinitely divisible interspike interval probability density function. PMID- 6249406 TI - Endorphins: naloxone failure to increase sexual arousal in sexually unresponsive women: a preliminary report. PMID- 6249405 TI - Oscillatory neural networks in the rabbit hippocampus. AB - A model is described to account for damped oscillatory activity of two interacting neural populations, pyramidal cells and interneurons. This network in the hippocampus is treated as a lumped system with time delays between elements. The physiological mechanism underlying the oscillatory activity appears to involve neural population interaction and cannot be described in terms of a network composed of but two neurons, a single pyramidal cell and a single interneuron. An unusual aspect of the model is the explicit incorporation of an ongoing background input to raise the mean level of activity of the pyrammidal cell population. This model has evolved from a series of studies previously performed on cats. To test the model experiments were performed on rabbits. The data showing oscillatory activity following fornix stimulation in the rabbit indicate that the model can be applied not only to the cat but also to the rabbit. In additions, for commissural stimulation oscillatory potentials of neural populations and individual pyramidal cells were evoked as predicted by the model. PMID- 6249408 TI - Temporal relationship between interstitial fluid accumulation and changes in gonadotropin receptor numbers and steroidogenesis in the rat testis. PMID- 6249407 TI - Prolactin, testicular growth and LH receptors in the ram following light and 2-Br alpha-ergocryptine (CB-154) treatments. PMID- 6249409 TI - Testosterone synthesis in rhesus fetal testes: comparison between middle and late gestation. PMID- 6249410 TI - Bromo and chlorobiphenyl metabolism: gas chromatography mass spectrometric identification of urinary metabolites and the effects of structure on their rates of excretion. AB - The identification of the hydroxylated rat urinary metabolites of the 2-, 3- and 4-chlorobiphenyls and 2-, 3- and 4-bromobiphenyls has been determined by gas chromatographic mass spectrometric analysis of their corresponding methyl ether derivatives. The electron impact fragmentation patterns of the bromotheoxybiphenyls and chloromethoxybiphenyls were used to assign the position of the methyoxyl group (ortho, meta or para to the biphenyl bond); the mass spectra of the corresponding [2H5]halobiphenyls confirmed the sites of the hydroxylation by distinguishing between the halophenyl and phenyl rings. The results illustrated that ring hydroxylation occurs predominantly at the para positions of the biphenyl nucleus and at sites which are ortho and para to the halogen substituents. 4,4'-Dimethoxyhalobiphenyls are major urinary metabolites of the 2- and 3-halobiphenyls and the rapid formation of these metabolites is illustrated in a time course study which monitors the urinary metabolites formed after the separate coadministration of the isomeric chlorobiphenyl and bromobiphenyl substrates to rats. PMID- 6249411 TI - Stereospecific elimination of deuterium as a method for determining the stereochemistry of a number of metabolites of the tetrahydrocannabinols. AB - The stereospecific elimination of the 3-deuterium atom from metabolites of [2H] analogues of delta 1-tetrahydrocannabinol (delta 1-THC), delta 6-THC and delta 7 THC has been investigated as a possible method for determining the stereochemistry of metabolites substituted with hydroxy or acid groups in the terpene ring. Elimination of HCOOTMS was found to involve the 3-hydrogen of the axial but not the equatorial isomer of hexahydrocannabinol-7-oic acid, a metabolite of all three cannabinoids. Similar stereospecific eliminations were observed during the loss of TMSOH from the TMS derivatives of 5 alpha-hydroxy delta 6-THC, 6 alpha-hydroxy-delta 1-THC and 1 alpha, 2 beta-dihydroxy-delta 1 THC. Loss of TMSOH from 1 alpha, 7- and 1 beta, 7-dihydroxy-HHC involved the 3 hydrogen in both cases but the isomers could be distinguished as their alkane boronate derivatives; only the derivative of 1 alpha, 7-dihydroxy-HHC lost the boronate ring with stereospecific removal of the 3-hydrogen. The stereochemistry of the four isomers of 1,6-dihydroxy-HHC could not be determined in this way as the [M-TMSOH]+ ions from all four compounds had lost the 3-hydrogen, presumably as the result of 1,6-bond cleavage. PMID- 6249412 TI - Why ATP instead of pyrophosphate? Interrelation between ATP and pyrophosphate production during evolution and in contemporary organisms. PMID- 6249413 TI - Structural and functional assembly of glycogen metabolizing enzymes. PMID- 6249414 TI - Hormonally stimulated adenylate cyclase: a membranous multicomponent system. PMID- 6249415 TI - Evolutionary aspects of the biological action of cyclic nucleotides. PMID- 6249416 TI - [Effect of cyclic guanidine monophosphate on experimental wound healing]. AB - Studies on the effect of cGMP on the proliferation of granulation tissue and collagenogenesis in experimental wound healing have shown that cGMP promoted more rapid formation and differentiation of fibroblasts rose thereby promoting an accelerated formation of collagen. Histological and biochemical findings correlated with wound planimetry data. In the course of stimulation the wound healing surfaces diminished more quickly as compared to the control. PMID- 6249417 TI - [Compensatory ovarian hypertrophy during alloxan diabetes and adrenoreceptor blockade]. AB - The sexual cycle ceases in rats with alloxan diabetes. Chronic administration of phentolamine promoted interruption of the sexual cycle while obsidan was conducive to its preservation in part of the animals. Most diabetic rats both given and not given adrenoblockers showed the complete absence of compensatory hypertrophy of the ovary (CHO). As shown by the analysis, the content of gonadotropins in the pituitary glands of diabetic rats was increased, with the response to chorionic gonadotropin being close to normal. It is suggested that the absence of CHO in most diabetic rats can be accounted for by the fact that after removal of one ovary the hypothalamohypophyseal system does not secrete gonadotropins in adequate amounts. PMID- 6249418 TI - [Stimulus dependent sodium channel blockade in node of Ranvier membranes by the quaternary antiarrhythmic N-propyl ajmaline (neogiluritmal)]. AB - The blocking action of neo-gilurytmal (NG), a quaternary derivative of aimalin, on sodium channels was studied in the voltage-clamped node of Ranvier. NG exerted no action on the resting membrane unless the repetitive pulsing was turned on. A series of repetitive depolarizing pulses of short duration (5 ms) produced the accumulating "stimulus-dependent" blockade of sodium channels. The rate and degree of the blockade increased with the increasing of pulse voltage even over the potential range where all the sodium channels were open. Recovery from the blockade occurred within several tens of minutes. Unlike the repetitive pulsing, long-lasting (1 s) depolarization of the membrane produced only a slight increase in the blockade of sodium channels. Elimination of sodium inactivation by aconitine prevented the blocking action of NG. The results of the experiments indicate that NG blocks only the open sodium channels with intact inactivation gate. PMID- 6249419 TI - [Effect of alkylating derivatives of cyclic adenosine-3' ,5'-monophosphate on proliferation of mouse bone marrow stem cells]. AB - The effect of the physiological concentration of cyclic adenosine-3' ,5' monophosphate (cAMP) analogues on the proliferation of mouse bone marrow stem hemopoietic cells (CFUs) was examined. The stimulating effect was estimated from the decrease in CFUs expressed in the percentage derived from comparing the number of spleen colonies in the control and experimental groups treated with hydroxyurea 10(-3) M (incubation with hydroxyurea resuted in the cell death in S phase). Cyclic AMP stimulted the proliferation of CFUs by 60%, while its analogues such as 8-(N-chloroacetylaminoethylamino)-cAMP, 1-(N chloroacetylaminoethyoxy)-cAMP and 1-(N-(p-fluorosulfonyl)-benzoylaminoethoxy) cAMP stimulated the proliferation by 39.2%, 32.4% and 21.9%, respectively. Therefore, the synthetic analogues of cAMP were not only far from inhibiting the proliferation of CFUs but, on the contrary, exerted a stimualting effect unlike most antineoplastic alkylating drugs that depress hemopoiesis up to its total aplasia. PMID- 6249420 TI - [Effect of thyrotropic hormone on the membrane potential of thyroid gland cells and thyroid hormone secretion with aging]. AB - Effect of thyrotropic hormone (TTH) on membrane potential (MP) of thyroid cells and thyroid hormone secretion was studied in experiments on male rats of two age groups (7--12- and 27--32-month-old animals). It was found that during the first 3 hours after TTH administration (5 U/100 g i. v.) the depolarization of secretory cell membranes of adult rats was done pronounced and developed more rapidly than in old ones and that an increase in free thyroxin (T4) correlation with MP changes with time. In a dose of 0.5 U/100 g TTH caused a significant rise in T4 secretion only in old rats. The cAMP level in the thyroid gland declined with aging. In a dose of 5 U/100 g TTH provoked a significant increase in the cAMP content in adult rats and had no effect on its content in old ones. A relationship between the MP level of thyroid secretory cells and thyroid hormone secretion is discussed. PMID- 6249421 TI - [Effect of a febrile response on adrenal cortex reactivity]. PMID- 6249422 TI - [Structural and functional changes in erythrocyte membranes in experimental atherosclerosis]. AB - Structural and functional characteristics of erythrocyte membranes were studied in rabbits with experimental atherosclerosis. In animals with single lipid spots in the aorta, a significant rise of the plasma cholesterol level was associated with the increased cholesterol/phospholipid (CS/PL) ratio and diminished activity of erythrocyte membrane Na+, K+-ATPase. EPMR spin probe data point to changes in structural membrane characteristics--an increase in order parameter for fatty acid chains of lipids and expansion of the temperature interval of the transition phase in the membranes. In rabbits with total aorta injury, a further increase both in the plasma cholesterol concentration and in the CS/PL ratio as well as in structural changes in erythrocyte membranes does not lead to another decrease in the enzymatic activity. In aorta homogenates of the experimental animals, the activity of Na+, K+-ATPase correlated with that in the erythrocyte membrane. This suggests the existence of similar chemical and structural changes in aorta cell membranes. The data may provide an indirect evidence in favour of the hypothesis of the involvement of smooth muscle cells and membrane enzymatic activity alterations in atherosclerosis. PMID- 6249423 TI - [Functional characteristics of nerve endings isolated from brain by the Hajos method]. AB - A study was made of the functional potentialities of synaptosomes isolated from the brain cortex and lumbar enlargement of the spinal cord. The yield of synaptosomes from the brain cortex amounted to 10 mg (with reference to protein) from 1 g of wet tissue, and that of synaptosomes from the spinal cord was equal to 1/3 of the yield from the brain, with the preparation being strongly contaminated with myelin scraps. Brain synaptosomes were marked by high level of respiration whose magnitude was affected by the agents (ouabain, high concentrations of K+ and benzylpenicillin) that change ion membrane transport. Synaptosomes maintained higher GABA gradient across the plasmatic membrane. Ouabain and potassium depolarization produced a considerable release of GABA and 3H-GABA into the incubation medium. A conclusion is made that the method of Hajos should be rather used for rapid isolation of the synaptosomal fraction from the rat brain cortex. PMID- 6249424 TI - [Study of the state of blood plasma by the spin probe method]. AB - To evaluate the potentialities of the spin probe method in examination of the blood plasma state, a study was made into the blood plasma bound nitroxyl radical 2,2,4,4-tetramethyl-1,2,3,4-tetrahydro-5,6-benzo-gamma-carbolin-3-oxyl in healthy rabbits and those with pronounced experimental atherosclerosis. The probe absorption by high molecular plasma components was assayed in order to determine the binding constants and concentration of the binding centers, mobility of adsorbed probes and polarity of their surroundings. In the course of experimental atherosclerosis development these parameters underwent changes correlating with those of blood plasma cholesterol level. The data obtained suggest that the spin probe method may be used for assessement of the plasma state for diagnostic and research purposes. PMID- 6249425 TI - [Inactivated sodium channels are blocked by the anti-arrhythmic cordaron]. AB - The blocking action of the antiarrhythmic cordaron (amiodaron hydrochloride) on Na currents in the frog node of Ranvier was studied by the voltage-clamp technique. It was established that the degree of the cordaron-induced block can be reversibly increased by long-term (1 s and more) membrane depolarization. The time constants of both the development and recovery from the block caused by membrane depolarization are of the order of hundreds of seconds ("induced slow sodium inactivation"). The fraction of blocked channels rises to some limiting level with an increase in the magnitude of the depolarizing step, the region of strong voltage dependency being between -130 and -70 mv. The inhibition of outward potassium current by 7.10(-4) M cordaron does not exceed 15%. The time- and voltage-dependent block of Na channels is supposed to result from interaction of the antiarrhythmic with inactivated channels. PMID- 6249426 TI - [Role of alpha- and beta-adrenoreceptors in isolated guinea pig trachea anaphylaxis to aerosol tick (D. pteronyssinus) allergy]. AB - Experiments were performed on inhalation-sensitized guinea-pigs, with the use of immunoallergic neurohistochemical techniques. Anaphylactic tracheobronchial spasm was shown to be related not only to the degree of sensitization but also to the state of alpha- and beta-adrenoreceptors. Sensitization, in its turn, changed the function of adrenoreceptors. It increased histamine sensitivity and decreased catecholamine sensitivity of an isolated organ. PMID- 6249427 TI - [Comparative karyologic study of transplantable MIO and MIO-r cells, sensitive and resistant to poliomyelitis virus]. AB - The continuous MIO cell line, highly sensitive to poliovirus, and the derivative subline MIO-r specifically resistant to this virus have been studied karyologically. It has been shown that these cell lines are different in modal class of chromosomes, mean number of the copies of individual intact chromosomes per cell and in morphology of marker chromosomes. PMID- 6249428 TI - [Effect of the functional state of adrenoreceptors on the mitotic activity of regenerating rat liver]. AB - Phentolamine, a blocker of alpha-adrenoceptors, given in a single dose (one hour before or 30 minutes, 8 and 24 hours after liver resection) decreased the mitotic index and the coefficient of mitotic phases, and elevated the glycogen content. The number of two-nucleated cells in rats exposed to phentolamine rose 8 hours after resection (p < 0.05). Obsidan, a blocker of beta-adrenoceptors, administered at the same periods, increased the mitotic index and the coefficient of mitotic phases. It is suggested that phentolamine prolonged the late mitotic phases, inhibiting the entry of the cells into mitosis. Obsidan elicited an opposite effect. PMID- 6249429 TI - Cryopreservation of human granulocytes: study of granulocyte function and ultrastructure. AB - Human granulocytes can be cryopreserved with dimethyl sulfoxide (DMSO) at--80 degrees C. However, the percent recovery of functional cells has been unsatisfactory to date. Throughout this study we have been able to prepare relatively pure granulocytes approximately equal to 85%), cryopreserve them with 5%--10% DMSO with and without serum, and store them at--80 degrees C for up to 4 mo. The parameters studied were absolute cell counts and viability determination, myeloperoxidase activity, phagocytosis, candidacidal activity, bactericidal activity, nitroblue tetrazolium reduction, chemiluminescence, and cell morphology by transmission and scanning electron microscopy. Based on our investigation, granulocytes cryopreserved without serum showed an intact membrane of superior integrity as compared with those preserved with serum. At least 50% of the cells recovered were functional after 2 mo of storage, but there was a progressive loss of viability and function on prolonged storage. The property of phagocytosis was the best preserved after storage for 4 mo, whereas myeloperoxidase activity, killing activity, nitroblue tetrazolium reduction, and chemiluminescence were maintained less efficiently. Morphological studies of cryopreserved granulocytes revealed that the nuclear, cytoplasmic, and cell surface architectures were altered by storage. Depletion of nuclear and cytoplasmic material, as well as changes in configuration, were also noted. PMID- 6249430 TI - Hemolytic anemia due to pyrimidine-5'-nucleotidase deficiency: report of eight cases in six families. PMID- 6249431 TI - An erythropoietic stimulating factor similar to erythropoietin released by macrophages after treatment with silica. AB - An erythropoietic stimulating factor (ESF) can be detected in the supernatant from fetal liver and adult bone marrow and spleen cells when preincubated with the macrophage-specific cytotoxic agent, silica. Stimulation is observed in 12 day fetal liver CFU-E cultures in the absence of added erythropoietin (Ep). The concentration of ESF in the supernatant added to CFU-E cultures is dependent on the preincubated cell dose and the volume added. The stimulating activity is abolished when mice are hypertransfused and increased above normal values when mice are bled. A concentrated silica-treated spleen supernatant was able to stimulate erythropoiesis in the polycythemic mouse bioassay. It is concluded that the ESF is similar, if not identical, to Ep. PMID- 6249432 TI - In vitro effects of cadmium and lead on ATPases in the gill of the rock crab, Cancer irroratus. PMID- 6249433 TI - Purine antagonists in the identification of adenosine-receptors in guinea-pig trachea and the role of purines in non-adrenergic inhibitory neurotransmission. AB - 1 To test the possibility that adenosine receptors exist within the trachea of the guinea-pig, an attempt has been made to identify a compound with adenosine antagonist activity in this tissue.2 Quinidine, phentolamine, phenoxybenzamine, 2 2'-pyridylisatogen tosylate (PIT) and caffeine were tested for antagonism of spasmolytic responses to adenosine, adenosine 5'-triphosphate (ATP) and adenine on the guinea-pig isolated trachea.3 Quinidine (10 and 25 mug/ml), phentolamine (10 and 30 mug/ml) and phenoxybenzamine (10 mug/ml) had little or no effect on response to adenosine, ATP and adenine. PIT (21 mug/ml) potentiated responses to adenosine, ATP and adenine by an unexplained mechanism.4 Caffeine (25 mug/ml) partially relaxed the trachea and inhibited spasmolytic responses to both adenosine and ATP, but not to adenine, isoprenaline, aminophylline or prostaglandin E(2) (PGE(2)).5 A number of compounds related to caffeine (xanthine, hypoxanthine, theophylline and theobromine) were tested for adenosine antagonist activity. Xanthine (300 mug/ml) and hypoxanthine (300 mug/ml) did not relax the trachea or antagonize spasmolytic responses to adenosine. Both theophylline (10 mug/ml) and theobromine (30 mug/ml) partially relaxed the trachea; theophylline, but not theobromine, antagonized spasmolytic responses to adenosine.6 pA(2) values for caffeine and theophylline as antagonists of adenosine were 4.3 and 4.7 respectively. However, the slopes of the Schild plot regressions were significantly less than 1.0 for both compounds.7 Four compounds, adenine, AH 8883, M30966 and ICI 63197, which like caffeine and theophylline, have phosphodiesterase inhibitory activity were tested for adenosine antagonist activity in the trachea. Adenine and AH 8883 had no effect and M30966 and ICI 63197 caused significant potentiation.8 The effects of caffeine and theophylline were also investigated on the non-adrenergic inhibitory response to nerve stimulation (NAIR). Both caffeine (100 mug/ml, n = 4) and theophylline (30 mug/ml, n = 4) enhanced the NAIR (20 Hz) while virtually abolishing matched responses to exogenous adenosine.9 The results support the existence of adenosine receptors in the guinea-pig trachea. PMID- 6249434 TI - Comparative study of the effects of 4-aminopyridine and tetraethylammonium on neuro-effector transmission in the guinea-pig vas deferens. AB - 1 Effects of 4-aminopyridine (4-AP) and tetraethylammonium (TEA) on the neuro effector junction of the guinea-pig vas deferens were investigated by microelectrode and double sucrose gap techniques. 2 4-AP (0.05 to 0.5 mM) or TEA (0.5 to 1 mM) did not alter the membrane potential, or the membrane input resistance of the smooth muscle cell. 3 The amplitude and frequency of the miniature junction potentials (m.e.j.ps) were not modified by treatment with 4-AP (0.05 to 0.5 mM) or TEA (1 mM). 4 4-AP (1 mM) increased the membrane input resistance, enhanced the spike amplitude of the smooth muscle cells and thereby augmented the amplitude of twitch contraction. 5 4-AP (.05 to 0.5 mM) or TEA (1 mM) markedly increased the amplitude of excitatory junction potentials (e.j.ps), but the facilitation phenomena produced by repetitive stimulation were not affected. 6 The duration of the extracellularly recorded action potential from the small nerve bundle was prolonged by 4-AP (0.5 mM). 7 The amplitude of the e.j.p. was dependent on the external concentration of calcium. A straight line was produced when the amplitude of the e.j.p. and [Ca]o was plotted on a double log scale. Application of 4-AP resulted in a parallel shift of this line to the left. 8 These results indicate that 4-AP (0.05 to 0.5 mM) and TEA (0.5 to 1.0 mM) prolonged the action potential generated from the sympathetic nerve terminal thus enhancing the amplitude of the e.j.p. due to an increase in the Ca-influx. However, in the concentrations used, these compounds did not modify the Ca mobilization in the nerve terminal or the postsynaptic membrane during the resting state. PMID- 6249435 TI - The effect of conditions influencing endogenous prostaglandins on the activity of delta'-tetrahydrocannabinol in mice. AB - 1 The cataleptic effect of delta'-tetrahydrocannabinol (THC) depends upon the availability of the precursors of prostaglandins and the response is reduced in mice maintained on a diet deficient in arachidonic acid (AA) and restored by exogenous AA given intraperitoneally, or by feeding a normal diet. 2 In yeast induced fever, which is accompanied by an increase in the synthesis of prostaglandins, THC shows an enhanced cataleptic effect. 3 Exposure to cold which results in depletion of prostaglandins reduces the effect of THC. PMID- 6249436 TI - A classification of opiate receptors that mediate antinociception in animals. AB - 1 To investigate the opiate receptors that mediate antinociception, the activity profiles of opioid analgesic drugs have been determined against different nociceptive stimuli in the mouse and rat. 2 In tests that employ heat as the nociceptive stimulus, mu-opiate receptor agonists, such as morphine, pethidine and dextropropoxyphene, had steep and parallel dose-response curves and were capable of achieving maximum effects. In addition, the antinociceptive potency ratios of these drugs in heat tests were similar to those for analgesia in man. 3 The kappa-agonists, such as ethylketazocine, nalorphine, Mr2034 and pentazocine, were essentially inactive against heat nociception except at doses that caused sedation and motor incapacitation. 4 In the writhing and paw pressure tests both mu- and kappa-agonists produced steep and parallel dose-response curves. 5 It is concluded that both mu- and kappa-opiate receptors mediate antinociception in animals and that the interactions of analgesic drugs with these receptors may be classified in terms of their antinociceptive activities against qualitatively different nociceptive stimuli. PMID- 6249437 TI - Prostacyclin-dependent activation of adenylate cyclase in a neuronal somatic cell hybrid: prostanoid structure-activity relationships. AB - 1 Prostacyclin activates adenylate cyclase of the NCB-20 neuronal hybrid cell line. 2 There is a guanosine 5'-triphosphate requirement for the activation of adenylate cyclase by 5,6 beta-dihydroprostacyclin (a stable analogue of prostacyclin). 3 Steady-state kinetic analysis of the activation of adenylate cyclase by 5,6 beta-dihydroprostacyclin suggests a simple non-cooperative bimolecular interaction between the ligand and single receptor population. 4 Structure-activity relationships of selected prostanoids elucidated certain functional requirements for activation of adenylate cyclase. PMID- 6249438 TI - A distinct form of adult polyglucosan body disease with massive involvement of central and peripheral neuronal processes and astrocytes: a report of four cases and a review of the occurrence of polyglucosan bodies in other conditions such as Lafora's disease and normal ageing. AB - We have described 4 patients with progressive lower and upper motor neuron deficits, marked sensory loss in the legs, 'neurogenic bladder', and, in 2 of the 4, dementia. Autopsy of two revealed a profusion of microscopic bodies resembling corpora amylacea or Lafora bodies, but restricted to processes of neurons and astrocytes. Similar (but especially large) bodies were seen within axons of sural nerves taken at biopsy from the other two patients. A general term--'polyglucosan body'--is introduced to refer to these structures in all the circumstances in which they may occur, such as in Lafora's disease, in a syndrome of longstanding double athetosis, in some cases of amyotrophic lateral sclerosis, in type IV glycogenosis, in diabetic rats, and in the normal course of ageing. Except in type IV glycogenosis, the causes for accumulation of polyglucosan bodies are unknown. They may damage tissue by more than one mechanism--probably by impeding axonal flow and impairing perivascular diffusion of metabolites. PMID- 6249439 TI - The role of GABA and serotonin in the mediation of raphe-evoked spinal cord dorsal root potentials. AB - The possible involvement of bulbospinal serotonergic systems in the mediation of analgesia has created a need for a better understanding of the influence this system has on neuronal mechanisms in the spinal cord. Therefore, these studies were designed to examine the effects of caudal raphe stimulation on primary afferent depolarization and to determine the role of serotonin (5-HT) and GABA in the mediation of these stimulation-produced effects. Stimulation of the raphe evoked two electrotonically conducted dorsal root potentials (DRP-1 and DRP-2) and two compound action potentials (VRP-1 and VRP-2) which were recorded from the dorsal and ventral roots, respectively. Length constant measurements indicated that DRP-1 was generated in group II and DRP-2 in group I primary afferent fibers. Histological determination of stimulation sites revealed that short latency potentials (DRP-1 and VRP-1) were evoked from many sites within the caudal brain stem, while the long-latency potentials (DRP-2 and VRP-2) were evoked primarily from sites within the caudal raphe nuclei. The role of serotonin in mediating these evoked potentials was assessed by administering various antagonists of serotonin (cinanserin, methysergide and D-lysergic acid diethylamide). These agents consistently attenuated the long-latency potentials (DRP-2 and VRP-2) but increased the magnitude of DRP-1. The possibility of a GABAergic neuron in the descending systems projecting to primary afferent terminals was studied. Depletion of GABA by semicarbazide blocked DRP-1, but had only a modest effect of DRP-2. However, the putative GABA antagonist, bicuculline, inhibited both DRP-1, and DRP-2. These results suggest that a GABA interneuron is not involved in the bulbospinal serotonergic depolarization of primary afferent terminals. This system appears to constitute a presynaptic filter of afferent input, with the capacity to inhibit different fiber groups. PMID- 6249440 TI - Angiotensin II-sensitive neurons in septal areas of the rat. PMID- 6249441 TI - Kainic acid neurotoxicity toward hippocampal formation: dependence on specific excitatory pathways. PMID- 6249442 TI - Synaptic organization of expansion motoneurons of Navanax inermis. AB - The opisthobranch mollusc, Navanax, feeds by rapid pharyngeal expansion that sucks in prey followed by peristaltic swallowing that moves prey into the esophagus. Several identifiable neurons on the ventral surface of the buccal ganglia control radial musculature within the pharyngeal wall, contraction of which leads to pharyngeal expansion. These are considered expansion motoneurons because their axons run into the muscle and twitches and EMGs occur one for one with action potentials. The motoneurons are electrotonically coupled. Electrotonic PSPs, the components of spread associated with impulses, can summate with subthreshold DC depolarizations to yield synchronous impulses in coupled cells. During a train of responses the later electrotonic PSPs can be facilitated because of increase in amplitude and duration of the presynaptic impulses. Expansion motoneurons are synaptically connected by two apparently interneuronal pathways: a low threshold pathway activated by subthreshold depolarization of the two largest expansion motoneurons (the G-cells) that inhibits the entire population, and a high threshold pathway that is activated by a train of G-cell impulses and produces largely excitatory PSPs in the smaller expansion motoneurons and an EPSP--IPSP sequence in the G-cells. Coupling among expansion motoneurons can be abolished by chemical inhibitory synaptic inputs that are activated by electrical stimulation of the pharyngeal nerve or tactile stimulation of the pharyngeal wall. This uncoupling phenomenon can be explained by a simple equivalent circuit in which inhibitory synapses along the coupling pathway short circuit electrotonic spread. Uncoupling can outlast the evoking stimulus by several seconds. During uncoupling the smaller expansion motoneurones can fire independently while the G-cell is inhibited, and impulses still propagate from somata to the periphery. The expansion motoneuron population receives excitatory input from the mechanoreceptors in protractor muscles. Mechanical stimulation of the pharyngeal wall activates primary sensory neurons in the buccal ganglia that fire during excitation and during inhibition and uncoupling of expansion motoneurons. PMID- 6249443 TI - Experimental allergic neuritis. I. Rat strain differences in the response to bovine myelin antigens. AB - Strain differences among rats to the induction and severity of experimental allergic neuritis (EAN) in response to whole PNS myelin were observed. Lewis rats were highly susceptible and developed severe EAN without central nervous system lesions (EAE), while Brown Norway rats were most resistant. Wistar, Sprague Dawley, and Buffalo rats were susceptible but developed less severe disease than Lewis rats. Only Lewis rats consistantly developed EAN in response to isolated P2 protein. The severity of EAN was enhanced by treatment of the P2 with mercaptoethanol prior to injection. None of the strains developed EAN in response to galactocerebroside and none developed the lesions of EAE in response to any of the bovine myelin antigens tested. Myelin protein profiles from these rat strains were similar which suggests that factors other than target tissue differences, such as genetically determined immune responses to bovine myelin antigens, must be involved in these differing responses. PMID- 6249444 TI - Intracellularly-recorded effects of glutamate and aspartate on neurones in the guinea-pig olfactory cortex slice. AB - The effects of bath-applied glutamate, aspartate (and some related amino acids) on neurones of the guinea pig olfactory cortex slice were recorded intracellularly. Neurones were activated either by intracellularly-applied current or orthodromically by stimulating the lateral olfactory tract. In response to orthodromic stimuli several neurones displayed a late hyperpolarizing potential (LHP) after the usual sequence of EPSP, spike and IPSP. Glutamate and aspartate evoked 3 types of response: (a) a depolarization with apparent increase in input conductance; (b) a depolarization with no detectable conductance change; and (c) a hyperpolarization with conductance increase. Some possible mechanisms by which these 3 response-types could be generated are discussed. Depolarizations evoked by the glutamate analogue, kainate, were usually irreversible. Our results emphasize that glutamate and aspartate can evoke a variety of neuronal responses from olfactory cortex neurones. Several of these responses were previously undetected in experiments based on extracellular recordings. PMID- 6249445 TI - Reduction of hippocampal acetylcholine turnover in rats treated with (-)-delta 8 tetrahydrocannabinol and its 1',2'-dimethyl-heptyl homolog. AB - The effects of (-)-delta 8-tetrahydrocannabinol (THC), (+)-delta 8-THC, and the dimethyl-heptyl (DMH) homolog of (-)-delta 8-THC (delta 8-THC-DMH) have been compared with the action of (-)-delta 9-THC on the turnover rate of acetylcholine in various brain areas. The data demonstrate that (-)-delta 8-THC-DMH, (-)-delta 9-THC and (-)- delta 8-THC all specifically reduce ther turnover rate of acetylcholine in the hippocampus in a dose-dependent manner ((-)-delta 8-THC-DMH > (-)-delta 9-THC > (-)-delta 8-THC) without altering the acetylcholine or choline content (except for high doses of (-)-delta 8-THC-DMH). The (+)-isomer of delta 8-THC fails to change any cholinergic parameter. The selectivity of action suggests that the tetrahydrocannabinoids may activate specific transmitter receptors which indirectly modulate the activity of the cholinergic neurons in the septal-hippocampal pathway. PMID- 6249446 TI - Does vanadate participate in the response of cerebral (Na+-K+)-ATPase to electrical stimulation. PMID- 6249447 TI - Effects of 4-aminopyridine on the frequency following properties of the parallel fibers of the cerebellar cortex. PMID- 6249448 TI - The dendritic varicosity: a mechanism for electrically isolating the dendrites of cat retinal amacrine cells? AB - Amacrine dendritic varicosities from cat retina were reconstructed using serial electron micrographs. Each varicosity contained a synaptic input and a synaptic output, suggesting that they may function as isolated local circuits. A passive steady state electrical model demonstrated that for a given conductance change the varicose dendrite maximizes the local membrane potential and minimizes th distance membrane potential change as compared to other possible dendritic shapes. We, therefore, suggest that the function of the varicosities on amacrine cell dendrites might be to electrically isolate these local input-output circuits. PMID- 6249449 TI - Potentiation by intraventricular muscimol of the anticonflict effect of benzodiazepines. AB - The anticonflict action of muscimol (a potent GABA receptor agonist) and its ability to potentiate the anticonflict action of the benzodiazepines was studied in rats using VOgel's procedure. Rats were injected intraventricularly with a dose of muscimol from 50 to 200 ng to study whether the anticonflict action was dose-related. The potency of a 200 ng dose of muscimol is comparable to the potency of an anticonflict dose of 0.5 mg i.v. of diazepam. THIP (a muscimol analogue with weaker intrinsic GABA-mimetic activity) is active in doses 10 times higher than muscimol. The threshold dose of diazepam (0.2 mg/kg i.v.) to elicit anticonflict action was markedly potentiated when it was injected 5 min after intraventricular muscimol (150 ng). These data support the concept that GABA receptors may be involved in the anticonflict effects of the benzodiazepines. PMID- 6249450 TI - Depressant and excitant effects of intraspinal microinjections of morphine and methionine-enkephalin in the cat. AB - The effects of intraspinal microinjectins of morphine (10 microgram) and methionine-enkephalin (Met-enkephalin) (5 microgram) on the C-fiber and polysynaptic reflexes in the acute decerebrate low spinal cat were investigated. Microinjected into the dorsal horn, morphine and Met-enkephalin depressed the nociceptive C-fiber reflex (CFR) without altering the short latency polysynaptic reflex. Microinjected into the ventral horn, morphine and Met-enkephalin facilitated the C-fiber and polysynaptic reflexes. Pretreatment of the cats with intravenous naltrexone (2 mg/kg) antagonized the depressant effects produced by dorsal horn intraspinal microinjections of morphine and Met-enkephalin. The excitant effects of ventral horn microinjections of morphine were not antagonized by naltrexone (2 mg/kg). These results support a hypothesis that the analgesic effects of morphine at the spinal cord level are due to interactions with opiate receptors in the dorsal horn. PMID- 6249451 TI - Dye-coupling betwen CA3 pyramidal cells in slices of rat hippocampus. PMID- 6249452 TI - Blockade of ACh potentials by alpha-bungarotoxin in rat superior cervical ganglion cells. PMID- 6249453 TI - Spontaneous discharges caused by increasing external Na ion or divalent cation concentration in the mouse dorsal root ganglion cells in culture. PMID- 6249454 TI - Electrophysiological analysis of taurine and glycine action on neurons of the midpuppy retina. I. Intracellular recording. AB - Intracellular recordings were carried out in the prefused retine-eyecup preparation of the mudpuppy. Taurine and glycine were added to the bathing medium to study their effects on different retinal neurons. In a few cases, gamma aminobutyric acid was exogenously applied to compare GABA vs taurine/glycine action. Receptors and horizontal cells were relatively insensitive to taurine/glycine, while amacrines and ganglion cells were comparatively more sensitive to these agents. Bipolar cells proved to be differentially effected by inhibitory amino acids: hyperpolarizing (OFF) bipolars were depressed by taurine/glycine and proved less sensitive to GABA; depolarizing (ON) bipolars were suppressed by GABA and were comparatively less sensitive to glycine/taurine. Taurine and glycine had identical actions on neurons and both were about equally effective at the same concentration. Strychnine blocked the action of taurine and glycine. The patterns of glycine/taurine sensitivity and their effects on second order neurons eliminate taurine as a photoreceptor transmitter; one or both of these agents may be utilized by a subclass of amacrine cells which interact with hyperpolarizing bipolars, other amacrine cells and ganglion cells. It appears that taurine or glycine or both may be selectively involved in OFF channel activity, while GABA may subserve an equivalent role for the ON channel. PMID- 6249455 TI - Electrophysiological analysis of taurine and glycine action on neurons of the mudpuppy retina. II. ERG, PNR and Muller cell recordings. AB - Extracellular electrophysiological recordings of the electroretinogram (ERG) and proximal negative response (PNR) were carried out in the perfused retina-eyecup prepartation of the mudpuppy. Intracellular recordingws were obtained from Muller cells. Bath-applied taurine/glycine had identical effects on the ERG, PNR and Muller cell responses and the effects of both agents were blocked by strychnine. Taurine and glycine suppressed the d-wave of the ERG, the OFF response of Muller cells and ON and OFF responses of the PNR. These observations show that taurine/glycine sensitivity is predominantly found in the OFF channel of the ERG whose underlying neuronal basis appears to be dark evoked depolarization of OFF bipolars. PMID- 6249456 TI - A comparison of the effects of localized brain administration of catecholamine and protein synthesis inhibitors on memory processing. AB - Protein synthesis inhibitors disrupt biosynthetic processes thought to control the formation of long-term memory. While the agents used (i.e. puromycin, acetoxycycloheximide, cycloheximide and anisomycin) do not selectively inhibit the synthesis of any particular class of protein, it has generally been hypothesized or assumed that the critical proteins(s) is structural and necessary for modification and/or growth of synapses. Recent reports indicated that all of the protein synthesis inhibitors causing amnesia inhibited tyrosine hydroxylase activity. Tyrosine hydroxylase is needed for the conversion of tyrosine to dopamine (DA) and norpinephrine (NE); altering the level of this enzyme could affect catecholamine (CA) turnover. Since drugs known to inhibit CA synthesis cause amnesia, it is of considerable interest whether amnesia induced by protein synthesis inhibitors depends basically on inhibition of CA synthesis. PMID- 6249457 TI - Angiotensin II responsive cells in the organum vasculosum lamina terminalis (OVLT) recorded in hypothalamic brain slices. PMID- 6249458 TI - Lack of cross-tolerance between morphine and Leu-enkephalin in the mouse vas deferens. PMID- 6249459 TI - Enkephalin-induced inhibition of hypothalmaic paraventricular neurons. PMID- 6249460 TI - Effects of amygdaloid stimulation upon trigeminal sensory fields of the lip that are established during hypothalamically-elicited quiet biting attack in the cat. AB - An experiment was performed in order to determine the role of the amygdala and surrounding cortex in quiet biting attack elicited from electrical stimulation of the hypothalamus. Stimulation of basal, cortical, and anterior amygdala as well as pyriform cortex and parahippocampal gyrus resulted in a suppression of the attack response and in a constriction of trigeminal sensory fields that are established during hypothalamic stimulation. Stimulation of lateral and central amygdala resulted in a facilitation of the quiet biting attack response and an expansion of the trigeminal sensory fields, and a decreased latency for the occurrence of jaw opening when the sensory field was held constant. These studies suggest that the amygdala modulated quiet biting attack behavior generated by hypothalamic stimulation at least, in part, by virtue of its control over sensory fields. PMID- 6249461 TI - Effects of stimulation of the substantia innominata upon attack behavior elicited from the hypothalamus in the cat. AB - Experiments were undertaken in order to determine the role of the substantia innominata and surrounding regions in quiet biting attack elicited from electrical stimulation of the hypothalamus in the cat. Stimulation from sites in the lateral aspect of the substantia innominata resulted in a suppression of quiet biting attack and in a constriction of the 'effective trigeminal sensory fields' established during hypothalamic attack site stimulation. Stimulation from sites situated more medially in the substantia innominata resulted in a facilitation of quiet biting attack and in an expansion of the 'effective trigeminal sensory fields'. The motor component of the jaw opening response was altered in only 50% of the cases in contrast to the consistent effects observed upon the 'effective sensory fields'. Electrical stimulation of the substantia innominata had little effect upon affective display elicited from the ventromedial hypothalamus. Stimulation from sites located in the nucleus accumbens had no effect upon hypothalamically-elicited quiet biting attack and inhibited the occurrence of affective display in 2 to 5 animals tested. These studied suggest that the substantia innominata differentially modulates quiet biting attack and accomplishes this, at least in part, through its effects upon sensory mechanisms associated with the jaw opening reflex. PMID- 6249462 TI - The action of 5-hydroxytryptamine on neuronal membranes and synaptic transmission in area CA1 of the hippocampus in vitro. AB - Cell membrane properties and synaptic transmission were examined by intracellular recording from the CA1 region of hippocampal slices during application of 5 hydroxytryptamine (5-HT). Seventeen cells (50%) showed an inhibitory response to 5-HT. The cells were hyperpolarized with decreased spontaneous activity and increased membrane conductance. The increase may be in potassium or chloride conductance. Synaptic transmission was not involved since Mg2+, Co2+ or Mn2+ did not block the response. 5-HT inhibited dendritic EPSPs by local postsynaptic effect. Four cells (11%) showed an excitatory response. They were depolarized while the spontaneous activity increased and the conductance decreased. The decrease may be in the potassium or chloride conductance. Two cells (6%) showed a mixed type of response with an early excitation and late inhibition. This respons may be a mixture of the two other responses or associated with a third type of 5 HT receptor. Eleven cells (33%) did not respond to 5-HT, but only in 3 of these 5 HT was applied in the soma region. In conclusion, 5-HT may inhibit dendritic excitatory synapses and decrease recurrent inhibition in hippocampus. PMID- 6249463 TI - Two reciprocating current components underlying slow oscillations in Aplysia bursting neurons. AB - The mechanisms of the slow oscillatory potential in burst firing neurons in the abdominal ganglion of Aplysia californica (L3-L6 and R15) were studied using voltage clamp methods, including a novel tract and hold technique. The steady state negative resistance characteristic (NRC) of these neurons is attributed to the activation of a moderately fast, persistent, inward current over a range of membrane potential below spike threshold. This inward current is quite sensitive to changes in external sodium concentration (Na)0 and insensitive to potassium (K)0. By contrast, the portion of the I-V curve below the NRC range is insensitive to (Na)0, but highly sensitive to (K)0. The results of 'track and store' voltage clamping show that there are actually two reciprocating currents whose combined action produces the slow oscillation. In addition to the inward current, there is a slow outward current which develops during the depolarized (burst) phase. The slow outward current can also be evoked, and more completely examined, with prolonged depolarizing voltage commands. The extremely slow decay of this current (tau approximately 45 sec) appears to be the factor underlying the slow, ramplike depolarization of Vm during the interburst interval. This slow outward current is insensitive to changes of (Na)0, but changes with (K)0 in a manner consistent with the Nerst equation. We conclude that the burst-inducing slow oscillations are generated as follows: a moderately fast inward sodium dependent current (INa) produces a regenerative depolarization, and this in turn, produces a much slower outward potassium current (IS) which hyperpolarizes the cell. The cycle is completed when IS has decayed sufficiently to allow Vm to depolarize enough to reactivate INa. We have used a quantitative version of this model to determine the time courses of gNa and gK throughout the oscillation, and to explain why different portions of the oscillatory cycle display 'graded' or 'all-or-none' behavior. PMID- 6249464 TI - Regional and subcellular localization of luteinizing hormone releasing hormone in the adult human brain. AB - The localization of luteinizing hormone releasing hormone (LHRH) in the post mortem adult human brain was investigated. LHRH was highly concentrated in medial basal hypothalamic tissue (1.14 ng/mg protein); lower levels of LHRH were present in tissue from the optic chiasm (0.05 ng/mg protein) and mammillary bodies (0.07 ng/mg protein). The concentrations of LHRH in hypothalamic tissue of men and women were similar. LHRH was undetectable (< 0.001 ng/mg protein) in the frontal cerebral cortex and cerebellum. When homogenates of the medial basal hypothalamus were fractionated on continuous or discontinuous sucrose density gradients, LHRH was found to be associated with subcellular particles. Upon examination by transmission electron microscopy, we found that these subcellular particles resembled isolated neuron terminals, i.e., synaptosomes. Low to undetectable amounts of LHRH were found in the cytosol or the myelin + microsome fraction of the gradients. The results of these studies are supportive of the view that LHRH is highly concentrated in neuron terminals of the adult human brain and may, therefore, be a central neurotransmitter or neuromodulator in the human. PMID- 6249465 TI - [(Na-K) ATPase activity and corticopapillary osmotic gradient in the kidney of rats with hereditary hypothalamic diabetes insipudus after administration of 1 deamino-8-arginine-vasopressin (DDAVP)]. PMID- 6249466 TI - A comparative study of the interaction of anionic, cationic and nonionic detergents with active site spin-labelled alpha-chymotrypsin and trypsin. PMID- 6249468 TI - [Changes in plasma electrolytes and their regulatory hormones during an acute exposure to heat. Human studies in a Finnish sauna]. AB - Plasma Na, K, Cl, Ca, P didn't or moderately be altered by exposure to acute heat in sauna bath (20 mn, 80 degrees C, relative humidity 15-20%). However, CO2T decreased, ARP, aldosterone, ACTH, PRL increased, and PTH wasn't modified. PMID- 6249467 TI - [Comparative study of the effects of carbachol, eserine and dibutyryl cyclic guanosine monophosphate on the behaviour of the cat]. AB - Carbachol and eserine injected into cerebral ventricles of conscious cats evoked aggressive behaviour accompanied with autonomic and motor phenomena. However, db cGMP also injected into cerebral ventricles of conscious cats elicited autonomic effects with miaowing, restlessness, ear twitching and scratching. When butyrate sodium and butyryc acide were injected intraventricularly no visible gross behavioural phenomena in conscious cats were observed. The gross behavioural effects of db-cGMP were substantially the same when the cats were pretreated by intraventricular injections of aminophylline. PMID- 6249469 TI - [Effect of the time of administration of 5-hydroxytryptophan on the restoration of circadian stimulation of ACTH secretion in rats treated with p chlorophenylalanine]. AB - In female rats kept under a photoperiod of 12L-12D (50 lux from 07.00-19.00 h) the pharmacological blockade of serotonin synthesis by pCPA (2 X 300 mg/kg i.p.) obliterated the diel ACTH stimulation, which could, however be restored by an additionnal 5-HTP injection (60 mg/kg i.p.), provided that the serotonin precursor was administered at 11.00 h. If injected at 23.00 h the same dosage of 5-HTP failed to elicit any increase in plasma ACTH. The circadian ACTH rhythm appears, therefore to depend upon a daily activation of the serotoninergic system occurring 4 h after the onset of the light phase. PMID- 6249470 TI - [Cardiovascular collapse after tracheal ligature in the rat]. AB - Tracheal ligature provokes in the Rat a cardiovascular collapse, the animal dying in 4 minutes. Pretreatment with phentolamine, an alpha-adrenergic blocker, increases the systemic arterial hypotension and shortens the survival time. PMID- 6249471 TI - Crystallinity of human pineal calcospherulites. AB - Crystallinity of mineral in human pineal calcospherulites was determined by electron spin resonance spectrometry after irradiation of the samples with gamma rays in a 60Co-source. The radiation-induced stable paramagnetic centers in the crystalline lattice of hydroxyapatite crystals were used as a marker of the crystalline fraction and related to the total mineral content. The crystallinity of pineal sand is higher than that of compact bone. The numerical value of the crystallinity coefficient depends on both the average crystal size of hydroxyapatite and the percentage of the crystalline fraction in the total amount of mineral. Literature data show that the average size of hydroxyapatite crystals in pineal sand are smaller than in bone tissue. It is, therefore, concluded that the higher crystallinity of pineal acervuli is due to the lower percentage of the submicrocrystalline fraction in their mineral. PMID- 6249472 TI - Effects of a bone resorptive factor from human cancer ascites fluid on rat bone cell calcium and cyclic AMP. AB - The effects of a bone resorptive protein isolated from human cancer ascites fluid on bone cell calcium and cyclic AMP were studied with fetal rat cells. The osteoclast-activating factor increased bone cell calcium uptake at 37 degrees C and 4 degrees C with no direct effects on calcium efflux. Concentrations of the resorptive factor that increased in vitro bone resorption and cell calcium uptake had no effect on cyclic AMP. The effects of the protein on calcium uptake were not specific for bone cells, and large increases were also observed in isolated fetal rat skin cells. These studies suggest that increases in the permeability of the cell membrane to calcium are involved in the mechanism of action of the ascites fluid resorptive protein. PMID- 6249473 TI - Effect of ACTH on PTH-stimulated bone resorption in vitro. AB - In vitro demonstration of PTH effects requires hormone concentrations greater than the "physiological" concentrations reported by radioimmunoassay or cytochemical assays. This discrepancy could be the result of binding or destruction of PTH at nonbiologically active sites. In the present study, ACTH was found to have no effect by itself on bone resorption, but addiction of ACTH to bone cultures together with low concentrations of PTH resulted in a specific enhancement of PTH-stimulated bone resorption. This effect was not observed when bone resorption was stimulated by PGE2 and 1,25(OH)2D3, and it was blocked by human serum. The effect of ACTH is similar to the enhancement in PTH-stimulated bone resorption by poly-l-lysine [7]. We suggest that the amplification of PTH stimulation was the result of displacement of PTH from nonbiologically active sites, making more PTH available for binding to its biologically active receptor. An alternative explanation for our results was that ACTH prevented degradation of PTH by bone-derived proteolytic enzymes. Thus the sensitivity of bioassays for PTH could be improved by adding ACTH. PMID- 6249474 TI - In vitro effects of vitamin D3 metabolites on rat calvaria cAMP content. PMID- 6249475 TI - Mineralization and metabolic response in serially passaged adult rat bone cells. PMID- 6249476 TI - Production of tumors in hamsters by cells of a pig uterine tube line. AB - Tumorigenicity was investigated in a pig established cell line continuously subcultured more than 400 times. Tumors were not found in hamsters' cheek pouches inoculated with cells from the first 200 subcultures. Fibroma developed in five out of 13 animals (9/26 pouches) inoculated with cells of the 313th and 314th subcultures. Two chromosome markers were found in the 290th subculture, in the 313th subculture inoculum and in tumor cells. PMID- 6249477 TI - AMP metabolism in the marine bacterium Beneckea natriegens. AB - The catabolism of AMP by preparations from Beneckea natriegens has been reexamined. In the absence of ATP, cell-free extracts catabolized AMP via adenosine to inosine. When ATP was present, adenylate kinase converted AMP to ADP, lowering the rate of AMP catabolism. Particle-free supernatants (225,000 x g) metabolized AMP alone slowly, but adenylate kinase was active when ATP was added. Washed particulate fractions contained AMP nucleotidase activity which converted AMP to adenosine; in the presence of ATP, adenosine formation was reduced by residual adenylate kinase associated with the particulate fraction. IMP was not detected as a metabolite in these experiments. PMID- 6249478 TI - Extracellular accumulation of L-glutamate in adenylyl cyclase deficient or cyclic AMP receptor protein deficient mutants of Escherichia coli. AB - An Escherichia coli cya mutant deficient in adenylyl cyclase and an E. coli crp mutant deficient in cyclic AMP receptor protein (CRP) accumulate substantial amounts of L-glutamate extracellularly when entering stationary phase of growth. The cya mutant grown in the presence of cyclic AMP accumulates little glutamate whereas the addition of cyclic AMP has no effect on glutamate accumulation in the crp mutant. It is proposed that an E. coli cell entering stationary phase requires a change in cell envelope structure which involes a cyclic AMP-CRP dependent process, and without this process the permeability of the cell membrane increases. PMID- 6249479 TI - Chemoreceptor tumors diagnosed at the Western College of Veterinary Medicine 1967 1979. AB - Twenty-nine chemoreceptor tumors submitted to the Western College of Veterinary Medicine, Saskatoon, Saskatchewan between 1967 and 1979 were compared with those previously reported. The prevalence was low, with 28 cases occurring in dogs while only one was diagnosed in a cat. Old male dogs and the Boxer, Boston bull terrier and Collie breeds were affected most commonly. The prevalence in Collies (five of 28 dogs) was unexpected but may have been coincidental in this size of sample. The chemoreceptor tumor was often of clinical significance because in two thirds of the cases it was either the presenting complaint or considered at necropsy to have caused illness or death. PMID- 6249480 TI - Chemotherapy for adenocystic carcinoma. AB - Seventeen patients with adenocystic carcinoma have received 34 adequate trials of chemotherapy at Princess Margaret Hospital since 1969. There have been five objective responses to chemotherapy in 4 cases, lasting from five to 24 months, and 3 other patients have had stabilized disease for a period of five to seven months. Responding and stabilized patients all had symptomatic improvement. Most responses were to 5-fluorouracil, the preferred drug for initial treatment of metastatic disease or locoregional disease that cannot be controlled by means of surgery or radiation therapy. PMID- 6249481 TI - Evaluation of vindesine and MER in colorectal cancer. AB - Vindesine, a derivative of vinblastine, was administered to 39 patients with advanced colorectal cancer refractory to 5-fluorouracil alone or in combination with other chemotherapeutic agents. The initial dose of vindesine was 4 mg/m2 administered intravenously (IV) over 30 minutes every two weeks. Tumor regression of more than 50% was seen in 2 and stable disease in 13 of 33 patients evaluable for response. Prior treatment with vincristine did not seem to influence response to vindesine. The median survival time was four months. The major toxic effect of vindesine was peripheral neuropathy, which occurred in 35% of patients who received two or more courses of treatment. Methanol extract residue of BCG (MER) was administered IV to 20 of 39 patients receiving vindesine without randomization in order to evaluate toxicities associated with IV MER. The most common toxic reactions to MER were fever and chills, while malaise and headaches were less common. Transient respiratory distress associated with appearance of reticulonodular pulmonary infiltrates occurred in 1 patient. Thus, MER at a dose of less than 1 mg/m2 did not seem to significantly influence the response rate to vindesine or the survival of patients. However, it appeared to ameliorate the myelosuppression caused by vindesine. PMID- 6249482 TI - Malignant melanotic neuroectodermal tumor: light and electron microscopic study. AB - An 11-year-old white boy had a melanotic neuroectodermal tumor of infancy (MNTI) in his right mandible. Gross-examination showed that the tumor had originated in the right lower dental nerve, destroyed the right mandible, infiltrated the surrounding soft tissues, and metastasized to several lymph nodes. The typical alveolar pattern was observed in most of the tumor mass; however, solid areas with neuroblastic features were present in the infiltrating and metastasizing portions of the tumor. Ultrastructural study demonstrated unequivocal neuroblastic and melanocytic differentiation. PMID- 6249483 TI - Large mitochondria in a pituitary adenoma with hyperprolactinemia. AB - A 27-year-old woman with amenorrhea following cessation of birth control pills was found to have a pituitary tumor which was secreting large amounts of prolactin. Many tumor cells had large mitochondria, the diameter of which ranged between 7 and 12 mu. Some tumor cells also displayed oncocytic transformation, and a few were definite oncocytes. The pathogenesis of mitochondrial swelling in pituitary tumors is discussed and the possible roles of prolonged intake of steroids and/or ischemia are suggested. PMID- 6249484 TI - Bronchial carcinoid tumor with ovarian metastasis: a light microscopic and ultrastructural study. AB - An unusual case of brochial carcinoid tumor with skin and bilateral metastases is presented. Histochemical stains and electronmicroscopic findings confirmed the diagnosis. The peculiar pathologic features and unique clinical characteristics are described. PMID- 6249485 TI - Hormonal receptor determination in juvenile nasopharyngeal angiofibromas. AB - Juvenile nasopharyngeal angiofibromas (JNA) are rare. They have been frequently treated with estrogens, either solely or as an adjuvant therapy prior to surgery or irradiation. Clinical trials have proveded no evidence to explain the objective respose to estrogens observed in some tumors. Since the mechanism of steroid hormone action is mediated via specific receptors, we analyzed 8 JNA for tumor cytosol estrogen receptors. None were positive for estrogen receptors. Additionally, all were also negative for progesterone receptors. Nasopharyngeal angiofibromas occur predominantly in adolescent boys at a time when there is a gradual change in androgen availability. Therefore, three latter angiofibromas were also analyzed for the presence of cytosol androgen receptor. Specific testosterone and dihydrotestosterone binding components in the tumor cytosol were detected. This observation raises for the first time the possibility that JNA may be an androgen-dependent tumor. Estrogen may act as an antiandrogen on these tumors, an action similar to that on prostate cancer. PMID- 6249486 TI - Vulvar Paget's disease: a topographic study. AB - Four vulvectomy specimens from patients with vulvar Paget's disease were studied by means of subserial total sectioning. In each case, the extent of histologically demonstrable disease was far greater than that of the visible lesion, the outline of the involved area was highly irregular, and multiple foci of disease were present. The implications of the findings for treatment selection, intraoperative management, and histogenesis are discussed. PMID- 6249487 TI - Treatment of feline leukemia and reversal of FeLV by ex vivo removal of IgG: a preliminary report. AB - Cats that were spontaneously infected with feline leukemia virus (FeLv) were treated with a combination of low-dose irradiation and extracorporeal immunosorption using formalin and heat-fixed S. aureus as a non-specific immunosorbent to remove plasma IgG and immune complexes. The treatment resulted in reduction of circulating lymphoblasts within two weeks and clinical improvement of three of the five animals. A reversal of the FeLV status is reported in five of five cats. Two of the five cats remain FeLV negative and completely tumor free seven and eight months post-therapy at the time of writing (July 1979). A third cat returned to an FeLV positive state but remained tumor free for 24 weeks. Another cat responded to the therapy by reduction of lymphoblasts and became FeLV negative but died of a hemorrhage during an immunosorption. The last cat's status was FeLV positive, then FeLV negative, and finally FeLV positive again. He died 20 weeks after initiation of therapy. During the treatment there was a weight gain in the three cats responding by tumor regression. The results are discussed in terms of a removal of some type of immunoinhibiting factors such as antigen-antibody complexes or suppressor molecules. PMID- 6249488 TI - Multifocal recurrent adult rhabdomyoma. AB - The clinical and morphologic features of a recurrent, multifocal, adult, extracardiac rhabdomyoma are reported. This benign skeletal muscle neoplasm is composed of large round to polyhedral cells containing cross striations. The ultrastructural features consist of hypertrophic Z bands, intranuclear inclusions, and numerous mitochondria with linear, intracristal inclusions. The low thymidine labeling index and long potential doubling time correspond wi th the length of time for clinical recurrence. PMID- 6249489 TI - Psychologic adaptation to breast cancer. AB - Adaptation to breast cancer depends on two parameters: one derived from the patient and one from the disease. The first comprises the psychological and social factors that are determined by the patient and her surroundings: the psychologic adjustment the patient had before illness, her social supports, especially her spouse, and her social context which will contribute to her need to hide her illness or encourage her sharing the loss with others, especially those who have had a similar experience. The other factor determining psychologic adjustment is contributed by the disease itself: the extent of spread, surgical operability, need for adjuvant therapy, the full application of rehabilitative measures, including plastic reconstruction when appropriate, and the psychologic management by the surgeon in the doctor-patient relationship. Each of these variables contributes to the emotional resources available to the woman and to the stresses that must be surmounted in adaptation to breast cancer; each can serve as a positive force or a negative one. At times, one strongly positive factor, such as family support, can counter several exceptionally negative aspects and result in a positive adjustment despite severe illness. Each variable will be discussed in relation to its contribution to an "adaptive readaptation" and optimal psychologic well-being despite illness, versus those factors that create a "maladaptive readaptation" with less than optimal psychologic well being. PMID- 6249490 TI - The use of aminoglutethimide in the treatment of patients with metastatic carcinoma of the breast. PMID- 6249491 TI - Nerve palsies: the preventable sort. PMID- 6249492 TI - In utero effects of 1,2-dimethyl hydrazine on adenosine and guanosine 3',5' cyclic monophosphate content in rat fetal intestine. AB - Sperm positive 12-14-day pregnant Holtzman rats were exposed to a single subcutaneous injection (20 mg/kg body wt) of 1,2-dimethylhydrazine (DMH). Two days post-exposure, the fetal intestinal tissues were examined for their content and metabolic activities for cyclic 3',5'-adenosine monophosphate (cAMP) and cyclic 3',5'-guanosine monophosphate (cGMP). The in utero exposure to the carcinogen resulted in lowering the intracellular content of cAMP and increasing cGMP. The decreased levels of cAMP may be accounted for the finding of a corresponding increase in its breakdown by its phosphodiesterases; however, associated with the increase in cGMP was correspondingly an increase in its phosphodiesterases, suggesting the activities for synthesis of this cyclic nucleotide may be the major factor for its elevated concentration. These observations indicate that DMH may cross the placental barrier and can effect the intracellular cyclic nucleotide concentrations in the fetal tissues as well as acting as a colorectal carcinogen in the adult rat. The changes in the cyclic nucleotide levels were toward the direction expected for an increased cell proliferation; consequently, further investigations are suggested to determine whether a hyperproliferative state is induced by the DMH in the already rapidly dividing fetal intestinal tissue. PMID- 6249493 TI - In search of an effective antiemetic: a nusring staff participates in marijuana research. PMID- 6249494 TI - Historical development and potential uses of tumor antigens as markers of human cancer growth. AB - During the past 30 years, the rapidly developing and changing concepts and technology of the discipline of immunobiology have been applied to studies in oncology. After the definitive demonstration of so-called tumor-specific transplantation antigens in chemically and virally induced tumors in syngeneic rodent and murine species, numerous efforts were then directed toward the demonstration of comparable materials in human tumors. After a number of false starts in an overzealous search for a marker that would serve as a panacea for human cancer diagnosis, more rational approaches have been taken to the problem and valuable information from the points of view of both the cell biologist and clinical oncologist has been forthcoming. The present paper presents an overview of human tumor antigens as biological markers of tumor growth. Reference is made to the fact that normally occurring biological materials of known function that are qualitatively and/or quantitatively altered during the process of malignant transformation may be most useful in the diagnosis and management of the cancer patient. The role of the presently available radioimmunoassays for carcinoembryonic antigen in clinical medicine is outlined. PMID- 6249495 TI - Use of isotopic immunoglobulin in therapy. AB - Antibodies raised in heterologous species against tumor-associated antigens such as ferritin and carcinoembryonic antigen may be utilized in diagnostic scanning and in cancer therapy. The radiolabeled (131I) antibodies have a mean effective half-life of 3 days. The tumor-bearing regions retain activity which was associated with objective evidence of remission in primary hepatic cancers. Major organ toxicity was not apparent in eight of nine patients treated with radioactive antibody. Objective evidence of clinical remission was documented by computer-assisted axial tomography scan remission in sequential studies that determine residual tumor in the same planar cuts. Future possible improvements in radioimmunoglobulin are discussed in light of the clinical findings. PMID- 6249496 TI - Correlation of 99mTc-pyrophosphate myocardial accumulation with left ventricular wall motion abnormalities. AB - Reports have indicated that myocardial accumulation of 99mTc-pyrophosphate occurs in the absence of a recent myocardial infarction. An attempt was made to determine if myocardial accumulation, in the absence of a recent infarction, may be associated with left ventricular wall motion abnormalities. 51 patients undergoing elective left ventriculography had 99mTc-pyrophosphate cardiac scans 24-28 h prior to the procedure. 33 (33/51) patients had myocardial accumulation; all 33 had left ventrcular wall motion abnormalities. Localized myocardial accumulation occurred in 21 (21/33) patients; 19 of the 21 had localized left ventricular wall motion abnormalities corresponding to the area of myocardial accumulation. 12 (12/33) patients had diffuse myocardial accumulation; 4 had diffuse left ventricular hypokinesis and 8 had localized myocardial dysfunction. 18 (18/51) patients had no myocardial accumulation of the radionuclide; 9 had normal wall motion in all areas and 9 had localized dysfunction. The data strongly suggest that myocardial accumulation of 99mTc-pyrophosphate in the absence of a recent myocardial infarction is associated with a left ventricular wall motion abnormality. PMID- 6249497 TI - Physical conditioning and membrane receptors for cardioregulatory hormones. AB - To seek possible mechanisms for the relative bradycardia induced by physical conditioning we studied the effects of an eight-week swimming programme upon cardiac beta-adrenergic and muscarinic-cholinergic receptors in rats. A training effect was documented by an increase in the ratio of heart wet weight to body weight in the conditioned animals compared with sedentary controls. Cardiac beta adrenergic receptors as assessed in crude membrane fractions by the binding of ( ) (3H) dihydroalprenolol did not differ significantly in either number or affinity in conditioned hearts (30 +/- 2 fmol.mg-1 protein; KD = 1.4 +/- 0.1 nmol.litre-1) compared with sedentary hearts (33 +/- 2 fmol.mg-1; KD = 1.5 +/- 2 nmol.litre-1). Likewise cardiac muscarinic-cholinergic receptors as assessed by the binding of (3H) quinuclidinyl benzilate to crude cardiac membranes did not differ significantly in either number or affinity in conditioned hearts (116 +/- 6 fmol.mg-1 protein; KD = 0.17 +/- 0.03 nmol.litre-1) compared with sedentary hearts (125 +/- 11 fmol.mg-1; KD = 0.19 +/- 0.03 nmol.litre-1). We conclude that the bradycardia of physical training is probably mediated by mechanisms other than alterations in cardiac beta-adrenergic or muscarinic-cholinergic receptors. PMID- 6249498 TI - [Scintigraphic diagnosis using 99mTc-labelled pyrophosphate (author's transl)]. PMID- 6249500 TI - Antibody-dependent cellular cytotoxicity to virus-infected target cells: role of nylon wool-adherent T cells as effectors. PMID- 6249499 TI - Cytological differentiation of the interrenal tissue of the Japanese quail, Coturnix coturnix. AB - As reported for several other avian species there are clearly distinguishable subcapsular (SCZ) and inner (IZ) zones of interrenal tissue in the Japanese quail. The SCZ contains large columnar cells (type I) with rounded nuclei, polymorphic mitochondria with shelf-like cristae, and relatively small numbers of lipid droplets. The IZ contains two and possibly three types of cells. Type II consists of large columnar cells with moderately dense cytoplasm containing large numbers of lipid droplets and many rounded mitochondria with tubular cristae. Smooth endoplasmic reticulum (SER) and Golgi apparatus are well developed; coated vesicles occur in Golgi area and at the cell surface. Type-III cells occur in IZ and especially in its more peripheral areas. They are columnar cells with strikingly clear cytoplasm (in comparison with type II) containing mitochondria with plate-like cristae and tubular SER. Type-IV cells are sparsely distributed in IZ and occur rarely in SCZ. Type IV may be a degenerating phase of type III. After adenohypophysectomy or section of portal vessels type-I cells atrophy somewhat with a decrease in lipid droplets; type-II cells, also atrophy with conspicuous increase in size and number of lipid droplets, enlargement of mitochondria, and gradual disappearance of Ser; type-III cells decrease in number whereas type-IV cells increase. After injection of ACTH, type-I cells enlarge and their mitochondria, SER and Golgi apparatus become more conspicuous; there is a decrease in lipid droplets in type-II cells and a development of SER, polysomes and Golgi apparatus; there is also a decrease in lipid droplets and a development of SER in type-III cells after injection of 2 IU ACTH and an almost complete disappearance of lipid droplets after 4 IU ACTH; type-IV cells increase in number. PMID- 6249501 TI - Gene inserts. Introns and exons, a condensed review. PMID- 6249502 TI - Electron microscopy of phospholipid vesicles reconstituted with purified renal Na,K-ATPase. AB - Purified Na,K-ATPase after reconstitution into phospholipid vesicles catalyzed an active coupled transport with a ratio close to 3Na/2K. A uniform population of closed vesicles with average diameters close to 900 A are observed after freeze fracture and thin sectioning. After freeze-fracture intramembranous particles with diameters of 80-100 A are observed. The data suggest that these particles correspond to Na,K-ATPase molecules. PMID- 6249503 TI - Loss of fibronectin in human breast cancer. AB - The distribution of fibronectin was studied in normal human breast tissue and in breast tumors. In normal tissues and in benign tumors, fibronectin was present in basal laminae and on the cellular surfaces of myoepithelial and secretory cells. A partial loss of (pericellular) fibronectin was seen in atypical dystrophies, and a complete disappearance of pericellular and basement membrane-bound fibronectin was observed in invasive adenocarcinoma. PMID- 6249504 TI - Immunohistochemical localization of cyclic AMP, cyclic GMP and calmodulin in Dictyostelium discoideum. AB - Using an indirect immunofluorescence technique cyclic AMP, cyclic GMP and calmodulin have been localized in Dictyostelium discoideum cells. The bound cyclic AMP is localized throughout the cell. Cyclic GMP and calmodulin are markedly localized in the nuclear area of the cell. No changes in the pattern of staining was observed during differentiation. Chemotactic stimulation induced a transient increase of cyclic GMP staining. PMID- 6249505 TI - Differential susceptibility of fibroblastic and non-fibroblastic surface fibronectins to periodate-borohydride labelling and enzymic treatment. AB - Surface labelling of liver epithelioid cells permits the detection of a 230,000 dalton component reactive with antifibronectin serum, when tritiated borohydride labelling is preceded by oxidation of sugar residues with galactose oxidase but not with sodium periodate. Similar experiments with liver fibroblasts lead to the labelling of a similar 230,000 dalton component both when sugar oxidation is carried out with galactose oxidase or periodate. Neuraminidase treatment prior to surface labelling lead to an increased labelling in both cell types, although a decreased labelling in the fibronectin region was apparent in the epithelioid cells. PMID- 6249506 TI - [Diagnosis and therapy of juvenile fibromas of the nasopharynx. Juvenile fibroma of the nasopharynx in an atypical locaction]. PMID- 6249507 TI - [An interesting case of chemodectomy of the head]. PMID- 6249508 TI - Human monkeypox, 1970-79. AB - Increasing attention has been given to human monkeypox since the achievement of global smallpox eradication. Monkeypox, which was first described in Central Africa in 1970, resembles smallpox clinically but differs from it epidemiologically. Forty-seven cases of human monkeypox have occurred since 1970 in 5 Central and West African countries; 38 of these cases have been reported from Zaire. The evolution of the illness and the sequelae of monkeypox and smallpox are the same; monkeypox has a case-fatality rate of about 17%. Children below 10 years of age comprise 83% of the cases. All cases have occurred in tropical rainforest areas and clustering of cases has been observed in certain zones within countries and within families. Person-to-person spread may have occurred in 4 cases; the secondary attack rate among susceptible, very close family members was 7.5% (3 cases/40 contacts) and among all susceptible contacts was 3.3% (4 cases/123 contacts)-much lower than the 25-40% secondary attack rate that occurs with smallpox. Although the low transmission rate and the low frequency of disease indicate that monkeypox is not a public health problem, more data are needed.Whilst many animals near human monkeypox cases have been demonstrated to have orthopoxvirus antibodies, the natural reservoir(s) and the vector(s) of monkeypox virus are unknown. Studies are in progress to identify the natural cycle of monkeypox virus and to define better the clinical and epidemiological features of this disease. PMID- 6249509 TI - Rotavirus and other viral diarrhoeas: WHO scientific working group. AB - Recent evidence indicates that viruses are an important cause of acute diarrhoea in infants and young children in both developed and developing countries. This article reviews the available information on the epidemiology, clinical features, and laboratory diagnosis of acute diarrhoea due to two of the more important and recently discovered viruses, namely rotaviruses and the Norwalk and Norwalk-like agents, or to other viral agents. Research priorities are also recommended that will help to elucidate the epidemiology, pathophysiology, and means of preventing viral diarrhoeas. Foremost among these research priorities is the development of a rotavirus vaccine for use in man. PMID- 6249510 TI - Injections and paralytic poliomyelitis in tropical Africa. AB - A case-control study was conducted in Yaounde, United Republic of Cameroon, to evaluate the hypothesis that intramuscular inoculations predisposed young children to paralysis if they were later exposed to poliomyelitis virus. Thirty three cases with lower motor neuron disease and 66 neighbourhood controls were studied. Poliovirus was isolated from 39% of the paralytic cases but from only 18% of the comparison group. Controls were more likely to have had serological evidence of previous exposure to all three poliovirus types while most of the paralytic cases had been exposed to a poliovirus for the first time. Two-thirds of the paralytic cases but only 11% of the comparison group had been ill, visited a medical facility, and received multiple injections, primarily with quinine and penicillin, in the month prior to the onset of poliomyelitis. There was a strong temporal relationship between these injections and the onset of paralysis. The increased relative risks (15 and 32, respectively) of paralysis associated with inoculations in the two weeks immediately prior to onset of disease were felt to represent the treatment of symptoms related to poliomyelitis. However, the increased relative risks (13 and 27, respectively) three and four weeks prior to onset were felt to be consistent with the hypothesis that intramuscular injections provoked paralysis. Overestimation of this measure of the effect because of bias in the control group is discussed. PMID- 6249511 TI - Neurological diseases associated with viral and Mycoplasma pneumoniae infections. AB - In 1963 the World Health Organization established a system for the collection and dissemination of information on viral infections and by 1976, laboratories in 49 countries were participating in this scheme. The present study is in two parts: part 1 is an analysis of almost 60 000 reports on neurological disease associated with viral and Mycoplasma pneumoniae infections reported during the 10-year period 1967-76. This analysis showed a steady increase in the yearly number of reports of viral neurological diseases, which closely followed the general increase in the overall reporting of virus diseases. Likewise, the seasonal pattern was similar to that seen in general for any given virus.Over 75% of the cases were in children. Over half of all viral neurological diseases were associated with enteroviruses, while the myxoviruses accounted for almost 30%. Among the myxoviruses, mumps virus was by far the most frequently reported. The polioviruses were the agents most commonly detected in cases of paralytic disease. The other enteroviruses, mumps virus, and the herpesviruses were the most frequently reported viruses in cases of aseptic meningitis or encephalitis. On the other hand, one-third to over one-half of the reports on the myxoviruses (excluding mumps and measles) related to ill-defined clinical conditions.Part 2 of the study deals in particular with viruses whose role in neurological disease is less well documented. One laboratory reported an outbreak of adenoviral aseptic meningitis in Czechoslovakia, while another described neurological disease associated with M. pneumoniae infection in Finland. Part 2 also includes a detailed appraisal of viral infections diagnosed in the Netherlands during the period 1973-76. The results are very similar to those routinely reported. PMID- 6249512 TI - [Nitrite reduction by NADH, catalyzed by the nitrite reductase of Pseudomonas aeruginosa]. AB - Reduction of nitrite by NADH catalyzed by Pseudomonas aeruginosa nitrite reductase is inhibited by a high concentration of nitric oxide NO. Contrary to what is currently admitted, we find that the nitrite reduction proceeds to the nitrogen monoxide N2O stage. EPR spectra show that, during the catalytic cycle, the enzyme forms specific Fe2+-NO heminic complexes. PMID- 6249513 TI - Experimental and clinical effect of ACNU in Japan with emphasis on small-cell carcinoma of the lung. AB - The experimental and clinical effects of ACNU so far recorded in Japan are reviewed. ACNU was highly effective in leukemia L-1210 and in other types of leukemias, ascites tumors, and solid tumors of mice and rats. On the basis of the results of phase I study, the maximum clinically tolerable single dose of ACNU was 101.8-135.7 mg/m2 at a time, and the total acceptable dose was 300-600 mg. The desirable interval between doses was 6-8 weeks. Phase II study revealed that ACNU seemed to be effective against small-cell carcinoma of the lung, brain tumors, Hodgkin's disease, and chronic myelocytic leukemia. In the treatment of small-cell carcinoma of the lung ACNU reduced the rate of brain metastasis and prolonged the survival of patients. PMID- 6249514 TI - Small-cell lung cancer. A curable disease. PMID- 6249515 TI - Use of sodium bicarbonate as a means of ameliorating doxorubicin-induced dermal necrosis in rats. PMID- 6249516 TI - Kaposi's sarcoma: a review and recent developments. PMID- 6249517 TI - The 4-O-methylation pathway of catecholamines: search for an in vivo production of 3-hydroxy,4-methoxyphenylglycol (iso-MHPG). AB - The existence of 3-hydroxy,4-methoxyphenylglycol in biological fluids has been investigated. 4-Hydroxy,3-methoxy-phenylglycol (MHPG) and 3-hydroxy,4 methoxyphenylglycol (iso-MHPG) have been separated from each other by gas-liquid chromatography of their heptafluorobutyryl derivatives, using an electron capture detector procedure. Urines of normal subjects, of patients with secreting nervous tissue tumors and human cerebrospinal fluids were analyzed. Iso-MHPG was never detected, with the exception of trace amounts in one urinary sample from a patient with a peculiarly high excretion of MHPG. It is concluded that norepinephrine is probably not 4-O-methylated in vivo, contrary to dopamine which is known to lead, at least to a small extent, to 4-O-methylated metabolites. PMID- 6249518 TI - A spin label study of the erythrocyte membranes in Duchenne muscular dystrophy. AB - Red blood cells and freshly prepared erythrocyte membranes of 15 patients with Duchenne muscular dystrophy (DMD) as well as age-matched controls were studied by the spin label method. No significant modifications appeared for spin-labelled proteins of ghost membranes. With the two fatty acid spin labels, 5-nitroxide stearate and 16-nitroxide stearate, we have confirmed previous results of Sato et al. concerning the thermal behaviour of the erythrocyte membranes, i.e. no change near the polar part probed by 5-nitroxide stearate and a linearization of the fluidity versus temperature variation around 12 degrees C, as explored by 16 nitroxide stearate. Furthermore we studied in the whole erythrocyte the amplitude of the 5-nitroxide stearate electron spin resonance signal as a function of the microwave power. This saturation effect was observed in 12 out of 15 controls and only in 1 out of 13 DMD cases studied. In erythrocyte membranes labelled with 16 nitroxide stearate the penetration of the label inside membranes was statistically different between DMD and controls. These new findings furnish further arguments in favour of a structural alteration of the phospholipid organization of erythrocyte membranes in DMD. Associated together, these different sets of tests obtained by spin labelling permit good statistical discrimination between DMD and normal subjects. PMID- 6249519 TI - Serum steroids and pituitary hormones in female puberty: a partly longitudinal study. AB - Pubertal development of 200 normal girls, 7--17 years of age, was investigated in a partly longitudinal manner with two examinations 1.5 years apart. Samples from postmenarchal girls were taken on days 6--9 and 20--23 of the menstrual cycle. Serum pregnenolone, progesterone, 17-hydroxyprogesterone, dehydroepiandrosterone, androstenedione, testosterone, 5 alpha-dihydrotestosterone, androsterone, oestradiol and cortisol as well as ACTH, FSH, LH and prolactin were measured radioimmunologically and were related to bone age, breast and pubic hair developmental stages, and gynaecological age. In the samples of premenarchal girls as well as the follicular phase of postmenarchal girls the concentration of all the steroids increased with age. Of all the steroids measured, serum dehydroepiandrosterone and pregnenolone displayed the earlier increase, from the youngest age group of 7.5 years onwards. Serum oestradiol testosterone and androstenedione in creased rapidly from the bone age group of 9.5 years (subjects 9.0--9.9 years of age) onwards, in close association with the appearance of the first physical signs of puberty. A marked increase in these three steroids continued until 13.5 years, the age at which menarche took place. Menarche was followed by a plateau of 1--2 years duration and then a second increase took place up to the two oldest age groups (17.5 and 18.5 years bone age), a trend seen in the follicular phase levels of all the steroids measured. The 5 alpha dihydrotesterone/testosterone ratio decreased with increasing testosterone concentration. Serum oestradiol, testosterone, androstenedione, dehydroepiandrosterone and FSH showed no overlapping in the 2.5--97.5% range of concentrations and androsterone and LH in the 16--84% range between prepubertal and postmenarchal subjects. Pregnenolone, progesterone, 17-hydroxyprogesterone, 5 alpha-dihydrotesterone, cortisol, ACTH and prolactin overlapped even in the 16- 84% range between these two groups of subjects. In postmenarchal girls, about 80% of the cycles were anovulatory in the first year after menarche, 50% in the third and 10% in the sixth year. The background of the majority of the anovulatory cycles seems to be a physiological variant of the pattern seen in the polycystic ovary syndrome: the levels of testosterone, and androstenedione and LH were increased in anovulatory cycles compared to ovulatory ones. PMID- 6249520 TI - An improved method for the detection of heterozygosity of congenital virilizing adrenal hyperplasia. AB - A modified short ACTH test for the detection of heterozygote carriers of 21 hydroxylase deficiency (21-OHD) was applied to twenty-one controls and fourteen parents of children with 21-OHD. The following modifications were introduced: (1) Endogenous ACTH was suppressed by dexamethasone administration prior to the test, (2) Plasma 17-hydroxyprogesterone (17-OHP), cortisol (F), progesterone (P), corticosterone (B) and delta 4- androstenedione (A) were measured, (3) Variables studied were the ratio of plasma increments (delta) between precursors and end products, (4) Data were analysed by a step-wise discriminant analysis. Significant alterations in the metabolic pathway of F, B and A were demonstrated. The discriminant analysis showed that the addition of B pathway data did not improve the discrimination potency of the test performed on F pathway data. The combination of variates which provided the best discrimination was the logarithmic sum of delta 170HP/delta F at 15 and 30 min. It led to a 94% correct classification for normals and carriers. PMID- 6249521 TI - The dose-response relationship of ACTH and cortisol in Cushing's disease. AB - The dose-response relationship between plasma ACTH and plasma cortisol was examined in normal subjects, patients with Addison's disease and patients with Cushing's disease. Plasma cortisol and ACTH levels were measured every half-hour from 06.00 h to 10.00 h and from 16.00 h to 18.00 h during a control day and during 1 to 3 days of continuous cortisol infusion. A plot of mean morning plasma ACTH versus the log of mean plasma cortisol revealed a similar dose-response relationship in normal and Addisonian subjects. Total plasma cortisol was four times more potent in suppressing mean morning ACTH in normal and Addisonian subjects, than in patients with Cushing's disease. When plasma cortisol was undetectable, there was no significant difference between mean morning ACTH concentrations in Addisonian patients and in adrenalectomized Cushing's patients. The glucocorticoid feedback control of ACTH in Cushing's disease had dose response characteristics similar to those in Addison's disease and normal subjects, except for decreased sensitivity to cortisol feedback suppression of ACTH. PMID- 6249522 TI - Adrenal steroidogenesis in hirsute women. PMID- 6249523 TI - Hormone precursors. AB - Evidence for the existence of multiple forms of various peptide hormones has been accumulated. The processing of the hormone precursors by cleavage at specific arginine or lysine residues can account for the presence of multiple forms. PMID- 6249524 TI - Hormone receptors in primary and advanced breast cancer. AB - The use of cytoplasmic ER is an integral part of the management of patients with metastatic breast cancer. Tissue from the primary tumour should be routinely assayed for ER and, when feasible, metastatic tissue should be obtained for assay. In addition, ER is an important prognostic variable for recurrence and overall survival and may be useful in the design of adjuvant therapy trials. Whether knowledge of receptor status correlates with chemotherapy response has yet to be conclusively determined. Whether PgR will ultimately add to the clinical usefulness of ER has also yet to be clearly defined; however, it is known that patients whose tumour contains both receptors have a high response rate to hormone therapy. These questions, and others await confirmation in prospective clinical trials. PMID- 6249525 TI - Hepatocellular carcinoma and type B hepatitis. PMID- 6249526 TI - Viral hepatitis type A: virology and course. PMID- 6249527 TI - Pathology of viral hepatitis and its sequelae. PMID- 6249528 TI - The influence of dibutyryl adenosine cyclic monophosphate on cell proliferation in the epithelium of the jejunal crypts, the colonic crypts and in colonic carcinomata of rat. AB - 1. Cell proliferation in the jejunal crypts, the colonic crypts and in dimethylhydrazine (DMH)-induced adenocarcinomata of rat colon was measured using a stathmokinetic technique. 2. Dibutryl cyclic adneosine monophosphate (dibutyryl cAMP) was found to inhibit cell proliferation in colonic crypts and in colonic adenocarcinomata. 3. Dibutryl cAMP at very high doses was found to inhibit jejunal crypt cell proliferation but at lower doses was found to accelerate jejunal crypt cell proliferation. 4. Neither bilateral adrenalectomy nor chemical sympathectomy was found to abolish the ability of dibutryl cAMP to stimulate jejunal crypt cell proliferation. 5. The present results are difficult to interpret in terms of known hormonal influences on cell proliferation in the tissues examined and of established actions, of these hormones on cyclic nucleotide metabolism in other tissues. PMID- 6249529 TI - Reversal of an abnormality of polymorphonuclear leukocyte chemotaxis with lithium. PMID- 6249530 TI - The effect of fatty acid addition in vitro on direct migration inhibition with paramyxoviral antigens. PMID- 6249531 TI - Pituitary pathology associated with abnormalities of prolactin secretion. PMID- 6249532 TI - Tc-99m-pyrophosphate accumulation on prosthetic valves. AB - Tc-99m-stannous pyrophosphate myocardial imaging has been one of the most effective and sensitive procedures for detection of acute myocardial infarction since Bonte et al introduced it in 1974. However, many causes of false-positive studies have also been reported since then. Presented here is an abnormal case of a patient with aortic and mitral valve replacement. PMID- 6249534 TI - Effects of delta 9-tetrahydrocannabinol on foot shock-induced aggression in rats. PMID- 6249533 TI - Influence of acid or alkaline treatment on tissue distribution and urinary excretion of (3H)-cocaine on acutely treated rats. AB - The effects of acid (NH4Cl, 60 mg/kg) or alkaline (NaHCO3, 400 mg/kg) pretreatment on tissue disposition and urinary excretion of (3H)-cocaine and its metabolites were assessed in rats. Animals were decapitated 4 hr after 1.9 microCi in 40 mg/kg cocaine (Cl-) in experiments on the biological disposition and the plasma, brain, and liver were assayed. In experiments on urinary excretion, 10 microCi were given and urine was assayed after 18, 24, and 48 hr. Pretreatment with NH4Cl produced a decrease of rates of cocaine + norcocaine in the brain as well as of the polar metabolites (benzoylecgonine, ecgonine benzoylnorecgonine). Forty-eight hours after injection of (3H)-cocaine, NH4Cl produced an increase of the rates of cocaine and its metabolites in the urine. Pretreatment with NaHCO3 causes a decrease of total radioactivity (cocaine + metabolites) in the plasma and in the liver, as well as a decrease of the levels of cocaine + norcocaine in the liver, as well as an increase of the rate of polar metabolites that are excreted in the urine. These data suggest that the decrease of pH after acid treatment produces ionization of basic molecules; these do not penetrate as well in the tissues for which they have no affinity. As a consequence, the urinary excretion is more important. It is possible that alkaline treatment accelerates the excretion of cocaine and its metabolites because it increases diuresis. PMID- 6249535 TI - Guidelines for short-course tuberculosis chemotherapy. U.S. Department of Health, Education, and Welfare, Public Health Service, Center for Disease Control Atlanta, Ga. PMID- 6249536 TI - Effects of parathyroid hormone and cyclic AMP on distal tubular calcium and sodium transport. PMID- 6249537 TI - Does parathyroid hormone cause protein wasting? PMID- 6249538 TI - Parathyroid hormone and the uremic manifestations. PMID- 6249539 TI - Metabolites of 24,25-dihydroxyvitamin D3 made in the kidney of chicks supplemented with vitamin D3. AB - Metabolism of 25-hydroxyvitamin D3 (25-OH-D3) was examined in chicks supplemented with vitamin D3. Kidney homogenates metabolized in vitro [3H]-25-OH-D3 to 3 new metabolites (peaks A, C and E) by way of 24,25-dihydroxyvitamin D3. The enzymes responsible for the synthesis of these metabolites appeared to be induced by 1 alpha,25-dihydroxyvitamin D3. Production of these metabolites was increased in parallel with the increase of the supplemented levels of vitamin D3, while recovery of the radioactivity in the chloroform phase was sharply decreased. The production of peak C was considered to be closely related to the transfer of the radioactive metabolites to the water-soluble phase. These results may indicate that 24-hydroxylation is a degradation step in the 25-OH-D3 metabolism. PMID- 6249540 TI - Vitamin D metabolism in hypophosphatemic vitamin D-resistant rickets. AB - Plasma levels of 1,25-(OH)2-D were low in children with hypophosphatemic vitamin D-resistant rickets (HVDRR), but increased after very large doses of 1 alpha-OH D3. These results suggest that the metabolism of 1,25-(OH)2-D is accelerated in HVDRR. In addition, the lower level of plasma 1,25-(OH)2-D in untreated HVDRR was correlated with the lower level of serum phosphate and renal threshold phosphate concentration (TmP/GFR). The administration of 1 alpha-OH-D3 to the patients with HVDRR could enhance the renal threshold phosphate concentration. PMID- 6249541 TI - Vitamin D and parathyroid hormone degradation by the kidney. AB - Parathyroid function is controlled by the regulation of hormone secretion as well as degradation, through the action of calcium and vitamin D derivatives. In order to clarify the relationship between vitamin D metabolism and parathyroid degradation system, parathyroid hormone (PTH)-degrading activities of the kidney were measured in vitamin D repleted and depleted rats given various derivatives of vitamin D. Kidney calcium content rose markedly in animals given 10 microgram/kg 1 alpha(OH) vitamin D3 and 1,000 microgram/kg dihydrotachysterol and PTH-degrading activity rose only in these animals, indicating a parallelism between kidney calcium content and PTH-degrading activity of the kidney tissue. These vitamin D derivatives also increased the PTH-degrading activity of kidney tissue when they were added in vitro. PMID- 6249542 TI - Urinary adenosine 3',5'-monophosphate, circulating amino-terminal PTH (1--34) and carboxyl-terminal PTH in hypoparathyroidism. AB - In 38 patients with hypoparathyroidism, electrolytes, amino-terminal PTH(1--34) and carboxyl-terminal PTH in serum and urinary cyclic AMP were measured. Serum PTH(1--34) levels were low and C-PTH levels measured simultaneously in the same sera were low except one having a high level. In pseudohypoparathyroidism, serum C-PTH was elevated and in 1 of 2 patients serum PTH(1--34) was elevated. Urinary cyclic AMP was decreased in hypoparathyroidism and there was a positive correlation between urinary cyclic AMP and serum PTH in normal subjects and parathyroid dysfunctions. Responses of urinary cyclic AMP to PTH were better in hypoparathyroidism and less in primary hyperparathyroidism than normal subjects. These data suggest that measurements of serum PTH(1-34), C-PTH and urinary cyclic AMP are important in the diagnosis and pathophysiological classification of hypoparathyroidism. PMID- 6249543 TI - Lung transplantation protection after warm ischemia and 1 day preservation. PMID- 6249544 TI - Regulation of oocyte maturation. PMID- 6249545 TI - Cytochrome c methylation: enzymology and biologic significance. PMID- 6249546 TI - Human phosphoglycolate phosphatase is coded by a gene on chromosome 16. PMID- 6249547 TI - Plasma aldosterone regulation in anephric and non-nephrectomized patients on regular haemodialysis. A survey. PMID- 6249548 TI - [Experimental assessment of the effect of chlorhexedine and sodium fluoride on enamel demineralization in perchloric acids]. PMID- 6249549 TI - Comparative mechanisms for contraction of cardiac and skeletal muscle. PMID- 6249550 TI - Ca2+ movements in smooth muscle. AB - We describe the Ca2+ movements in smooth muscle cells at rest and during activation and relaxation as deduced from transplasmalemmal Ca2+ fluxes and contractile respnses. The general picture which emerges is: the resting cell has a [Ca2+]cyt below 10(-7) M and large gradients are poised across both the cell membrane and intracellular membranes. Excitation opens up Ca2+ channels which are linked to receptors and, if depolarization occurs, to other channels not linked to specific receptors but capable of sensing the membrane potential. Receptor activation also leads to release of Ca2+ from a limited intracellular Ca2+ pool which is superficially located because it has to be refilled from the outside. Relaxation is effected by Ca2+ accumulation by another intracellular Ca2+ pool, very likely sarcoplasmic reticulum, which does not release Ca2+ during activation. The sarcoplasmic reticulum Ca2+ pump can also decrease initial activation of the myofilaments. Elevation of cAMP levels may inhibit contraction by stimulating the sarcoplasmic reticulum Ca-ATPase. An enormous amount of research is still required to prove the above scheme and to localize and quantitate the various intracellular Ca2+ pools. PMID- 6249551 TI - Pharmacology of agents that affect calcium. Agonists and antagonists. AB - Calcium utilization by smooth muscle is briefly reviewed. A variety of stimulant evoked calcium mobilization processes exist including utilization of intracellular Ca2+ and translocation of Ca2+ through voltage-sensitive and insensitive channels. The extent of use of these several sources is both stimulant and tissue-dependent and it is probable that most smooth muscle excitation-contraction coupling processes employ more than a single Ca2+ source. A large number of agents have been described as "Ca2+-antagonists" and ideally there would exist antagonists specific for each mobilization process. This does not appear to be the case and the structural diversity of the many antagonists is consistent with multiple modes of action. Prominent among the Ca2+ antagonists are agents as verapamil, D600 and nifedipine which have as one component of their action inhibition of voltage sensitivie Ca2+ channels. However, the mechanisms by which these agents act are unknown and it is also clear that they have important effects at sites other than Ca2+ channels. PMID- 6249552 TI - Infantile spasm. A clinicoelectroencephalographic report of 41 cases. PMID- 6249553 TI - Experience in resection of small hepatocellular carcinoma. PMID- 6249554 TI - Hypoglycemia: insulinoma or islet hyperplasia? PMID- 6249555 TI - [Abrikosov's tumor. Observation of a case with double localization]. PMID- 6249556 TI - Effects of reovirus infection on the spatial and temporal organization of DNA replication in L cells. AB - DNA fiber autoradiography was used to analyze the spatial and temporal organization of activated initiation sites for DNA replication in mouse L929 cells infected with reovirus type 3 (Dearing strain) and in uninfected control cells. Cells were labeled for 10 min with 3H-thymidine at high specific activity followed by 3 h of low specific activity labeling. Reovirus infection causes no change in the rate of replication fork progression, but increases both the mean distance between activated initiation sites by approximately 30% and the nonrandomness in the spatial distribution of the sites along the DNA fibers. Significant synchronization of initiation in adjacent activated sites was detected on DNA fibers from uninfected cells and from reovirus-infected cells. The mean relative initiation time for pairs of initiation events which had occurred prior to high specific activity labeling did not differ significantly between the infected and uninfected cells. The data are consistent with the interpretation that reovirus infection shuts off initiation sites in a coordinated fashion, possibly by preventing activation of entire clusters of potential initiation sites. PMID- 6249557 TI - Primary linitis plastica of the rectum. AB - Five cases of primary linitis plastica of the rectum are presented. The clinical, radiologic, and pathologic features of the disease are described with emphasis on the difficulty in establishing a correct preoperative diagnosis. Because the histologic features of primary and secondary linitis plastica are indistinguishable and because secondary involvement is twice as common as primary, it is mandatory that other sites of origin are excluded and that both the proximal and distal margins of the resected area be free of tumor. PMID- 6249558 TI - Effects of bisacodyl on cAMP and prostaglandin E2 contents, (Na + K) ATPase, adenyl cyclase, and phosphodiesterase activities of rat intestine. AB - The hypothesis that bisacodyl induces inotestinal fluid accumulation by increasing mucosal PGE2 content, inhibiting (Na + K) ATPase, and stimulating adenyl cyclase activities was tested in rats. Eighteen hours after its intragastric administration, bisacodyl (5.9 mg/kg body wt) decreased significantly jejunal and colonic (Na + K) ATPase activity: 36.4 +/- 1.4 (SE) and 28.3 +/- 1.4, respectively, as compared to 42.1 +/- 1.6 and 37.0 +/- 2.9 mumol/mg protein/hr in saline-treated rats. Bisacodyl administration increased significantly jejunal and colonic PGE2 content and stimulatd jejunal and colonic adenyl cyclase activity as compared to those in control rats. Jejunal and colonic cAMP content was not significantly increased by bisacodyl. Four hours after its administration, bisacodyl increased intestinal PGE2 content but failed to stimulate adenyl cyclase activity. Pretreatment with indomethacin prevented the increase in PGE2 content and the stimulation of adenyl cyclase induced by bisacodyl. Only jejunal phosphodiesterase activity was stimulated by bisacodyl (10 mg/kg body wt). The results reported thus suggest that intestinal inhibition of (Na + K) ATPase activity, increase of mucosal PGE2 content, and possibly also stimulation of adenyl cyclase activity might contribute to the net water accumulation induced by bisacodyl. It is also suggested that the stimulation of adenyl cyclase activity is mediated by increase in mucosal PGE2 content. PMID- 6249559 TI - The influence of delta 9-tetrahydrocannabinol on intraocular pressure in the anaesthetized cat. AB - delta 9-Tetrahydrocannabinol (delta 9-THC) was injected both intravenously and into the brain stem via the left vertebral artery. Contrary to results obtained with clonidine, neither the fall in intraocular pressure (IOP), nor the arterial hypotension induced by delta 9-THC, were enhanced after the 'central' administration of the drug. For clonidine, a central mechanism underlying the ocular hypotensive effect has recently been proposed. This suggestion is based upon the enhanced fall in IOP after 'central' administration of clonidine. The pontomedullary area is considered to be the main initial target of this drug. Obviously, the IOP-lavering mechanism of delta 9-THC is different from that of clonidine. PMID- 6249560 TI - [Determination of the location of the initiation site of replication and of ribosomal genes on a restriction map of Misgurnus fossilis loach mtDNA]. PMID- 6249561 TI - [Mammalian DNA sequences related to the src gene of Moloney virus and their mapping]. PMID- 6249562 TI - [Experimental infection of fattening calves with bovine adenovirus type 4 (author's transl)]. PMID- 6249563 TI - [Serological investigations for detection of neutralising antibodies against the virus of Aujeszky's disease in pedigree breeding - and piglet producing farms in the district of the Animal Health Office in the Chamber of Agriculture Weser-Ems (author's transl)]. PMID- 6249564 TI - [Comparing investigations for detection of antibodies against transmissible gastroenteritis (TGE)-virus by use of the microneutralization test, the indirect immunofluorescence test and the virus inhibition test (author's transl)]. PMID- 6249565 TI - Epidemiology of acute gastroenteritis in early childhood in Kenya. III. Distribution of the aetiological agents. PMID- 6249566 TI - Mesenteric dermoid cyst simulating hepatocellular carcinoma in a Nigerian male: a case report. PMID- 6249567 TI - Binding of THS by normal and TSI-containing globulins. AB - 125I-TSH was found to be specifically, bound to globulins from healthy persons and from patients with Graves' disease (GSI negative). Bmax 1.2 pmol mg-1, Kd 1.2 mga pmol-1 was found for TSI negative globulins from normal sera and Bmax 32 pmol mg-1, and Kd 53 pmol-1 mg for TSI positive ones. Maximum binding appeared within a 1 incubation period and was little dependent on temperature. The pH optimum for the binding was found between 7--8. There was a linear correlation between the protein content and the specific binding of the globulin preparations. LH, FSH, ACTH, prolactin and insulin competed with TSH for the binding sites only in relatively very high concentrations. The binding sites appear to be macromolecules, since they were eluted from Sephadex G-200 at the void volume. PMID- 6249568 TI - Cellular mechanism of the angtigonadotropic action of luteinizing hormone releasing hormone in the corpus luteum. PMID- 6249569 TI - A longitudinal hormonal profile of the genetically obese mouse. AB - Obese mice (C57BL/6J ob/ob) and their lean littermates were studied at various ages from immediately post weaning until 62 weeks of age, at which mortality increased markedly. Several age-related changes were noted. 1) Plasma glucose levels were elevated in obese mice 5-20 weeks and 62 weeks of age, but were similar to those in the lean mice at 20-60 weeks of age. Plasma insulin levels were elevated in obese mice, and there were no age-related differences. 2) Brain serotonin was elevated in obese mice at all ages and increased with age in both obese and lean animals. 3) Pituitary contents of ACTH and beta-endorphin were elevated in young obese mice and increased further as these mice approached their life expectancy. 4) The ratios of ACTH to beta-endorphin immunoreactivities were similar in obese and lean mice, except in obese mice over 50 weeks of age where this ratio was increased. We conclude that: 1) the obese mouse is characterized by hyperinsulinemia and hyperadrenocorticism throughout its life; 2) the insulin resistance of the obese mouse improves at 20 weeks of age, yet deteriorates as its life expectancy is approached; 3) the obese mouse has an elevated brain serotonin content similar to previously described elevations of the putative neurotransmitters dopamine and norepinephrine in these mice; and 4) as the obese mouse approaches its life expectancy, abnormalities may occur in the synthesis, processing, or secretion of ACTH and/or beta-endorphine. PMID- 6249570 TI - Modulation by thyroid status of the glucagon receptor-adenyl cyclase system in rat liver plasma membranes. PMID- 6249571 TI - Regulation of pituitary receptors for gonadotropin-releasing hormone during the rat estrous cycle. AB - A radioiodinated superagonist analog of gonadotropin-releasing hormone (GnRH:[D Ser(TBu)6]des-GLy10-GnRH N-ethylamide) was used to quantitate the GnRH receptor content of single pituitary glands. This ligand binds with high affinity (Ka = 4.9 X 10(9) M-1) to a single class of sites in pituitary homogenates, without significant tracer degradation, during equilibration for 80 min at 4 C. The GnRH receptor content of adult male rat pituitaries [112 +/- 6.4 (SE) fmol/gland; n = 9] was similar to that of adult female rat pituitaries obtained at estrus or metestrus (104.8 +/- 6.4 fmol/gland, n = 13). Between 1800 h on metestrus and 1800 h on diestrus, the pituitary content of GnRH receptors increased to 200 fmol/gland or greater in each of three separate experiments. The pituitary content of GnRH receptors remained elevated until the time of the serum LH surge, then consistently fell sharply to metesterus levels. These data imply a physiological relevance for the GgRH-binding sites measured by radioassay and demonstrate their relationship to the events of the estrous cycle. The increased GnRH receptor content from the evening of diestrus until late in the afternoon of proestrus may contribute to the enhanced sensitivity of the pituitary to GnRH during proestrus. The close temporal relationship between rising blood estrogen levels and increasing pituitary GnRH receptors suggests that steroid-mediated receptor induction occurs before proestrus. Such an effect of estrogen could be exerted directly upon the pituitary gland or indirectly via the hypothalamus to increase the release of endogenous GnRH, which subsequently induces its own receptors in pituitary gonadotrophs. PMID- 6249572 TI - Interaction of equine luteinizing hormone with binding sites for follicle stimulating hormone in the rat seminiferous tubule. PMID- 6249573 TI - Development of responsiveness of dispersed rabbit adrenocortical cells to synthetic adrenocorticotropic hormone [ACTH-(1-24)] and alpha melanocyte stimulating hormone. AB - Although there is a considerable body of evidence suggesting increased activity of the fetal and neonatal adrenal in the rabbit, the mechanism responsible for this increased activity has not yet been determined. This report provides data on the function of dispersed fetal, neonatal, and adult rabbit adrenocortical cells in vitro. During the period between 22-29 days gestation, the fetal rabbit adrenal cortex increases its cell number and three features of in vitro activity: basal corticoid production, responsiveness to synthetic ACTH-(1-24), and maximum corticoid secretory capacity. None of these variables is significantly altered during the first 3-5 days of neonatal life or in adult rabbits. At no time was any corticoid response observed to alpha MSH. PMID- 6249574 TI - Prolactin receptor content of rabbit milk. AB - Rabbit milk fat globule membranes have been shown to contain PRL receptors by a variety of criteria, including hormonal specificity and inhibition by specific anti-PRL receptor antisera. Collection of milk samples throughout the period of lactation facilitated a temporal study of the receptor content of the membrane fraction of these milk samples by Scatchard analysis after treatment with 5 M MgCl2 to dissociate endogenously bound PRL. Total receptor content was low after parturition (3.3 +/- 1.3 fmol/mg membrane protein) but increased subsequently, reaching maximal levels (43.7 +/- 3.4 fmol/mg) by day 21 of lactation. No significant difference in the Ka (4.9 X 10(9) +/- 0.35 M-1) of the milk receptor was detected over a 4-week suckling period. No apparent relation seemed to exist between rabbit serum PRL values measured by RIA in serum samples taken just before milking and milk PRL receptor content. Milk receptor content, however, was significantly (P < 0.02) correlated with the PRL receptor content of the gland when animals were sacrificed immediately after milking. PMID- 6249575 TI - Marihuana inhibits dihydrotestosterone binding to the androgen receptor. AB - Marihuana and its constitutents delta 9-tetrahydrocannabinol (delta 9-THC) and cannabinol (CBN) were tested for their ability to interact with the androgen receptor in rat prostate cytosol. Smoked marihuana condensate, delta 9-THC, and CBN inhibit specific binding of dihydrotestosterone (DHT) to the androgen receptor with a dissociatin constant of the inhibitors (Li) of 2.1-5.8 X 10(-7)M. in addition, other metabolites of delta 9-THC were also androgen antagonists. This data suggests that the anti-androgenic effects associated with marihuana use results, at least in part, from inhibition of androgen action at the receptor level. PMID- 6249576 TI - Properties and localisation of rabbit alveolar macrophage 5'-nucleotidase. AB - 5'-Nucleotidase has been demonstrated in rabbit alveolar macrophages. This enzyme has been found to be localised on the plasma membrane as have alkaline phosphodiesterase I and leucyl-2-naphthylamidase. Heterogeneity of the plasma membrane has been evidenced by the behaviour of these enzymes during isopycnic centrifugation. PMID- 6249577 TI - On the role of inorganic phosphate in divalent-cation sequestration by mitochondria. AB - Rat liver mitochondria which have actively accumulated Mn2+ ions exhibit an electron para-magnetic resonance (EPR) spectrum dominated by a component E in which the usual hyperfine sextet has been collapsed to a single line through the process of spin exchange narrowing. When uptake occurs in the absence of added Pi, the line width of E shows considerable variation. By comparing experimentally observed spectra with computer-generated simulations it is demonstrated however that, under these conditions, E can be as narrow as approximately equal to 190 Oe, considerably narrower than the spectrum from a manganese phosphate precipitate. Furthermore parallel quantification on a single mitochondrial sample shows the level of Pi to be several times lower than the amount of Mn2+ observable in E. It is concluded therefore that the spectral component E, obtained under these conditions, cannot be accounted for in terms of manganese phosphate precipitate. These findings further indicate that a substantial number of sites (approximately equal to 100 nmol/mg protein), other than Pi, must exist inside the mitochondria which are capable of complexing divalent cations in regions of high local concentration. PMID- 6249578 TI - Relative increase in polysomal mRNA for R1 cAMP-binding protein in neuroblastoma cells treated with 1,N6-dibutyryl-adenosine 3',-5'-phosphate. AB - Polysomal RNAs were isolated from control neuroblastoma cells and those treated with 1,N6-dibutyrl-adenosine 3',5'-phosphate (Bt2cAMP) and translated in wheat germ lysates. Comparison of proteins synthesized in vitro on two-dimensional gel electrophoretograms showed that there was a specific induction in the synthesis of a protein, Mr 48000, by the polysomal RNAs from Bt2cAMP-treated cells. This protein was identified as the R1 cAMP-binding protein by its coelectrophoresis with unlabelled binding protein and by its specific retention on 8-(6 aminohexylamino)-adenosine 3',5'-phosphate linked to Sepharose. Quantification of the proteins synthesized in vitro with subsaturating inputs of polysomal RNAs showed that there was a 1.4--1.7-fold increase in the synthesis of the R1 cAMP binding protein by polysomal RNAs isolated from Bt2cAMP-treated cells. There was a similar increase when purified polyadenylated mRNA populations were compared. showing there was no change in the ratio of adenylated to nonadenylated mRNAs in the induced mRNA population. There was no corresponding increase in the synthesis of the R2 cAMP-binding protein although the relative synthesis of several other proteins was also increased and the synthesis of actin and the alpha and beta tubulin subunits was decreased. The increased levels of the R1 cAMP-binding protein found in Bt2cAMP-treated neuroblastoma cells are therefore partly caused by a specific accumulation of its mRNA on polysomes. The mRNA content of the cytoplasmic messenger ribonucleoprotein (mRNP) population of control cells was insufficient to account for this increase by a translocation of R1 mRNA from the mRNP to the polysome fraction in Bt2cAMP-treated cells. The increase in polysomal R1 mRNA is therefore caused by its increased transcription of post transcriptional processing or its decreased rate of degradation in Bt2cAMP treated cells. Although the R1 and R2 binding proteins have identical molecular weights and similar pI values, the specific induction of the mRNA for R1 cAMP binding protein and the differential distribution of the R1 and R2 mRNAs between the polysomal and messenger ribonucleoprotein compartments show that these two cAMP-binding proteins are encoded by different mRNA populations. PMID- 6249579 TI - Investigations on the possible involvement of phospholipids in the glucose-6 phosphate transport system of rat-liver microsomal glucose-6-phosphatase. AB - Interrelationships between the catalytic behavior of glucose-6-phosphatase and the structure of rat-liver microsomal membranes were investigated. 2. Rabbit anti microsomal serum completely inhibited glucose-6-phosphate hydrolysis in detergent modified microsomes but showed no inhibitory effect on the enzyme activity of intact or mechanically disrupted vesicles. 2. Controlled proteolysis of intact microsomes using carboxypeptidase A and/or aminopeptidase M largely denatured enzymes situated on the outer surface of the microsomal vesicles such as monodehydroascorbate reductase and cytochrome c reductase. However, it did not affect the glucose-6-phosphatase activity at all, which remained in a latent state within the membrane. 3. Temperature studies on glucose-6-phosphatase have revealed that only the enzyme activity of intact microsomes exhibited a nonlinear Arrhenius plot, whereas detergent-modified microsomes showed a linear temperature response. 4. Treatment of microsomes with phospholipase C and toluene-2,4 diisocyanate resulted in an apparent loss of about 65% and 85% of the original glucose-6-phosphatase activity and was closely correlated with hydrolysis and chemical modification of phosphatidylethanolamine, respectively. These apparent inactivations could be reversed by addition of Triton X-114 alone without any phospholipid supplementation. These observations indicate that glucose-6 phosphatase is buried within the microsomal membrane, not exposed on either side. They also suggest that phospholipids are involved in the glucose-6-phosphate transport mechanism. PMID- 6249580 TI - Amplification of a mitochondrial DNA sequence in the cytoplasmically inherited 'ragged' mutant of Aspergillus amstelodami. AB - A comparison has been made between mtDNA of the cytoplasmically inherited 'ragged' mutant of Aspergillus amstelodami and that of the wild-type strain. Ragged mitochondria contain both the wild-type mitochondrial genome and several large DNA molecules which are not cleaved by the restriction endonucleases BamHI, HaeIII, HhaI, HindII, HindIII, PstI and MboI, but are converted by either EcoRI or HpaII into a single 820-840 base-pair fragment. Restriction analysis and molecular hybridization data indicate that this fragment contains sequences of wild-type mtDNA located within a 1200-base-pair segment of the 40,500-base-pair genome, for which a basic restriction map has been deduced. It is concluded that in the ragged mutant a small segment of wild-type mtDNA has been amplified as tandem repeats, which is reminiscent of the Rho- petite phenotype of yeast. The results are discussed in relation to the phenomenon of senescence in Podospora anserina. PMID- 6249581 TI - Purification and characterisation of adenosine-3',5'-phosphate-independent protein kinase from wheat germ. AB - cAMP-independent protein kinase was isolated from the wheat germ and purified to electrophoretic homogeneity. The molecular weight of enzyme was approximately 20,000, Km for ATP was (1 +/- 0.2) x 10(-5) M. V was 215 nmol phosphate mg enzyme 1 min-1, and the isoelectric point was at pH 9.2. The enzyme promotes phosphorylation of casein and crude wheat germ ribosomes. PMID- 6249582 TI - Binding and inhibitory effect of 2-heptyl-4-hydroxyquinoline-N-oxide in the presence of ubiquinone-3 in Saccharomyces cerevisiae. AB - 1. 2-Heptyl-4-hydroxyquinoline-N-oxide (HpHOQnO) binds to oxidized mitochondria of Saccharomyces cerevisiae with a dissociation constant of 5 x 10(-8) M and with a ratio of 1 mol per mol cytochrome b. 2. After addition of 171 micro M ubiquinone-3 to oxidized mitochondria, 0.3 mol HpHOQnO bind to 1 mol cytochrome b. The binding strength of the inhibitor is not essentially affected. 3. Reduction of mitochondria with succinate results in a strong decrease of the HpHOQnO binding. The dissociation constant could not be calculated on the basis of the applied method. 4. On the basis of the inhibitory effect of HpHOQnO on reduced mitochondria, a dissociation constant of 5 x 10(-6) M is calculated. 5. The respiratory electron flow to oxygen is about 100 times as sensitive to HpHOQnO as the electron flow to cytochrome c. 6. Ubiquinone-3 reverses the inhibition by HpHOQnO and stimulates the electron flow. 7. The different influence of ubiquinone-3 in binding and in inhibition experiments is discussed as a result of redox conditions. PMID- 6249583 TI - Steroid receptors and effects of oestradiol and progesterone on chick oviduct proteins. AB - After a single injection of oestradiol benzoate (1.5 mg/kg) to oestrogen withdrawn chickens, there was an increase in magnum wet weight, DNA polymerase alpha activity, adenosine-3',5'-monophosphate-dependent protein-kinase activity and estrogen-receptor concentration, as measured over 36 h. Besides these intracellular proteins, the secretory proteins ovalbumin and conalbumin were also augmented, and detailed time-course studies were performed. Early induction kinetics for ovalbumin and conalbumin synthesis, which differed for each protein, were independent of the dose of oestradiol benzoate injected if it exceeded 0.1 mg/kg. After 6 h for ovalbumin and 2 h for conalbumin, the induction curves diverged according to the dose of hormone administered and in correlation with the persistence of elevated nuclear oestrogen-receptor concentrations, a result confirmed with 11 beta-methoxy-17 alpha-ethynyloestradiol (R 2858), a powerful synthetic oestrogen. When oestradiol benzoate (1 mg/kg) and progesterone (3 mg/kg) were injected simultaneously, the rate of conalbumin sythesis, during the first 6-8 h, was lower than that observed in animals injected with oestradiol benzoate alone. However at later times conalbumin synthesis was greater in animals receiving both hormones than with oestradiol alone. In contrast, the rate of ovalbumin synthesis after the combined injection was higher than that induced by either hormone alone throughout the entire experimental period. In order to study further the synergistic and antagonistic activities of these two hormones, a single injection of progesterone (3 mg/kg) was administered 6, 12 or 18 h after 1.5 mg/kg oestradiol benzoate. Progesterone administration resulted in a reduction in cytoplasmic, nuclear and total oestrogen receptor concentration for at least 6 h when compared with the values in birds treated with oestrogen alone. DNA polymerase and protein kinase activities were also reduced during this period. Subsequently, all parameters increased, and by 18-24 h after progesterone treatment, reached values higher than those observed in animals receiving oestrogen alone. PMID- 6249584 TI - Demonstration of specific receptors of the rough endoplasmic membrane for the signal sequence of carp preproinsulin. AB - 1. Evidence is given for the cotranslational processing in a wheat germ cell-free system of carp preproinsulin to proinsulin by dog pancreatic rough endoplasmic membranes stripped of ribosomes by EDTA. Concomitantly with processing there is a translocation of the protein across the membrane as shown by the accessibility to proteases. Conversion of preproinsulin to proinsulin occurs post-translationally only in the presence of detergent. 2. Stripped rough endoplasmic membranes bind a significant proportion of the cell-free translation products synthesized in a wheat germ system in response to poly(A)-rich RNA from carp islets. Among the bound material there is completed preproinsulin. The bound material is accessible to proteases. It is located on the cytoplasmic side of the membranes. Peptides lacking a signal sequence, such as globin or proinsulin, are not bound. The binding can be abolished by pretreatment of the rough membranes with proteases. Neither smooth endoplasmic membranes from dog pancreas nor erythrocyte plasma membranes from rabbits are able to bind signal peptides. The binding sites on the rough membranes can be saturated with cell-free products coded by carpislet RNA and are then no longer able to process preproinsulin to proinsulin in a contranslational assay. The amount of membranes necessary to bind a certain amount of cell-free products post-translationally corresponds roughly to the amount required for complete conversion of preproinsulin to proinsulin cotranslationally. The binding phenomenon occurs independently of the presence of ribosomes and is not sensitive to high ionic strength. A hydrophobic peptide (Ac Lys-Phe-Phe-Gly-Leu-Nle-NH2) did not compete with signal peptides. 3. The results show that stripped rough endoplasmic membranes possess specific protein containing receptors for signal sequences on their cytoplasmic side. The recognition of the signal by the endoplasmic membranes occurs without participation of the ribosomes. The latter are only required for the translocation of the nascent peptide into the lumen of the membrane. PMID- 6249585 TI - The relationship between intramitochondrial N-acetylglutamate and activity of carbamoyl-phosphate synthetase (ammonia). The effect of glucagon. AB - 1. The relationship between urea synthesis, intracellular N-acetylglutamate and the capacity of rat-liver mitochondria to synthesize citrulline was investigated. 2. Treatment of rats with glucagon prior to killing results not only in an increased intramitochondrial ATP concentration and an increased capacity of the mitochondria to synthesize citrulline, but also in an increased concentration of intramitochondrial N-acetylglutamate. 3. Comparison of the rate of citrulline synthesis in mitochondria from glucagon-treated and from control rats, incubated under different conditions, shows that the increased N-acetylglutamate concentration after glucagon treatment is at least in part responsible for the observed increased capacity of the mitochondria to synthesize citrulline. 4. Ureogenic flux in isolated hepatocytes under different incubation conditions correlated with the intracellular concentration of N-acetylglutamate and with the capacity of the mitochondria to synthesize citrulline. 5. When isolated hepatocytes were incubated with NH3, ornithine, lactate and oleate, intracellular N-acetylglutamate increased about eightfold in the first 10 min; during this period the rate of urea synthesis increased considerably. 6. It is concluded that the concentration of intramitochondrial N-acetylglutamate plays an important role in the short-term control of flux through the urea cycle under different nutritional and hormonal conditions. PMID- 6249587 TI - The ganglioside content of the milk fat-globule membrane and the mouse mammary tumour virus isolated from the milk of infected mice. Partial characterization of a new disialoganglioside. AB - The milk fat-globule membrane and the mouse mammary-tumour virus isolated from the milk of infected Swiss mice have been investigated for their content in gangliosides. When compared on the lipid phosphorus basis, viral envelope is found to contain more than twice as much lipid-bound sialic acid as fat-globule membrane. The ganglioside patterns of these two structures appear rather similar, except for the occurrence in fat-globule membrane of a low ganglioside homolog, presumably GM2, not detected in viral envelope. A common and dominant trait is the presence in both structures, as the main ganglioside, of a component which has been so far characterized as a disialoganglioside, having the same neutral glycolipid moiety as GD1a, but with both sialic acid residues displayig to Clostridium perfringens and Vibrio cholerae neuraminidase, the susceptibility typical of terminal sialic acid residues. PMID- 6249586 TI - On the role of dihydroorotate dehydrogenase in growth cessation of Ehrlich ascites tumor cells cultured under oxygen deficiency. AB - In pyrimidine biosynthesis the oxidation of dihydroorotate is catalyzed by dihydroorotate dehydrogenase, which is linked to the mitochondrial electron transport chain in vertebrates. In order to elucidate the role of this oxygen dependent anabolic process in the arrest of cell proliferation under anaerobic culture conditions, the effect of the antimetabolite dihydro-5-azaorotic acid on growth, metabolism and cell cycle distribution of Ehrlich ascites tumor cells was studied and compared with the effect of oxygen-free culture conditions. Experiments with cell homogenates confirmed that the dehydrogenation of dihydroorotate is blocked by the inhibitor. In intact cells 2 mM dihydro-5 azaorotic acid inhibited incorporation of dihydro[6-14C]orotate into nucleic acids, and no further increase in RNA and DNA content was observed in its presence for several hours. The cells remained viable; glycolytic activity was normal; respiration was reduced; growth cessation occurred within a few hours. DNA histograms obtained by flow cytometry revealed an accumulation of cells in the G1 phase, which was also observed with anaerobically cultured cells. Substitution of cultures with pyrimidine nucleosides completely sustained cell proliferation in the presence of the inhibitor but not in an anoxic atmosphere. It is concluded that in the absence of oxygen cell proliferation may be arrested by inhibition of the dihydroorotate dehydrogenase alone. However, additional impairments of cell metabolism must play an important role. PMID- 6249588 TI - Spin-label study of histone H1-DNA interaction. Comparative properties of the central part of the molecule and the N and C-amino tails. AB - Covalent spin labelling of lysine and arginine residues in histone H1 under specified conditions allows the study of histone-DNA interaction. When the labelled histone is free in solution, the electron spin resonance spectrum is characteristic of a label moving in a viscous medium while the label becomes fully immobilized upon the interaction of histone and DNA. This property is used to study histone-DNA interactions under various conditions of ionic strength and thermal denaturation. On the other hand, spin label probes in the globular part of the molecule shows no strong immobilization upon binding to linear DNA, suggesting a special mechanism for the binding of histone H1 to chromatin. PMID- 6249589 TI - Phosphorylation of plasma membrane proteins dependent on adenosine 3',5' monophosphate in rat-glial C6 cells. PMID- 6249590 TI - A study of the mechanism of ferritin formation. The effect of pH, ionic strength and temperature, inhibition by imidazole and kinetic analysis. AB - The rate of ferritin formation in the buffers 4-morpholinepropanesulphonic acid (Mops), 4-morpholineethanesulphonic acid (Mes) and imidazole at pH values from 5.0 to 6.5 is quite similar. However, the rate of iron deposition is much greater in Mops and Mes at pH values above 6.5 than in imidazole. Increasing the concentration of imidazole inhibits ferritin formation and also leads to a transformation in the shape of the kinetic curves observed. This inhibiton is also observed at constant ionic strength but is not found for non-complexing buffers such as Mops. An inhibition of ferritin formation in imidazole and in Mops buffers is also observed with increasing ionic strength. We conclude that the unprotonated form of imidazole inhibits iron deposition, possibly by binding to the active site of the apoferritin molecule. The temperature dependence of iron deposition was examined. An optimum temperature of 50 degrees C was found but the Arrhenius plots were non-linear. On the basis of these and previous results, a kinetic model is developed which accounts well for ferritin formation at pH values below 6.5 and above 7.0 in non-complexing buffers. The model does not account for the kinetics observed at pH values close to neutrality. PMID- 6249591 TI - Simultaneous decrease in deamination of 5'-adenylic acid and 5'-deoxy-5'-S isobutylthioadenosine in chick-embryo fibroblasts infected by Rous sarcoma virus. AB - The rate of deamination of 5'-deoxy-5'-S-isobutylthioadenosine [(iBuS5'Ado] in chick embryo fibroblasts was substantially reduced after their infection and morphological transformation by Rous sarcoma virus. Concomitant with the reduction in rate of (iBuS)5'Ado deamination there was a decrease in adenosine deaminase and 5'-adenylic acid deaminase activities. The drop of these activities was related to infection and not to the expression of the src gene. (iBuS)5'Ado was deaminated by at least three enzymes or isoenzymes whose apparent molecular weights have been estimated to be 295000, 121000 and 37000 respectively. Two of these enzymes have been characterized as 5'-adenylic acid deaminase and the heavy form of adenosine deaminase, respectively. PMID- 6249592 TI - Cytochromes c-556 from three genetic races of Agrobacterium. Purification and comparison of their properties. AB - 1. The soluble cytochromes c-556 from three strains of Agrobacterium tumefaciens, B6, II Chrys and Apple 185 have been purified to homogeneity. The strains are representative members of the three main genetic races of Agrobacterium. The purity of the final preparations was established by electrophoresis with an without sodium dodecyl sulphate, by analytical isoelectric focusing and ultracentrifugation, and by N-terminal analysis. 2. Properties of these cytochromes were compared wih those of cytochrome c-556 from A. tumefaciens, strain B2a, a member of the same genetic race as strain B6. The four cytochromes are monohaem proteins with molecular weights of about 12300 (determined by four different methods). The isoelectric points of those from strains B6 and B2a are identical at pH 5.5, but they differ from the cytochromes of the other genetic races: cytochrome c-556 from strain Apple 185 is more acidic (ph 5.2) and that from strain II Chrys more basic (pH 6.2). The cytochromes from strains b6 and B2a have very similar but not identical amino acid compositions; both of them differ more from Apple 185 than from II Chrys c-556. 3. Comparison of the tryptic, chymotryptic and thermolytic fingerprints of cytochrome c-556 from strains B2a and II Chrys reveals strong homology between the primary structures of these cytochromes. Therefore and because of the sequence identity of the first eight residues, the cytochromes c-556 from strains II Chrys, B6 and B2a are most likely C-terminal haem-bound, of the same type as the cytochrome c' from photosynthetic bacteria. PMID- 6249593 TI - Purification and properties of hamamelosekinase. AB - Hamamelosekinase (ATP:hamamelose 2(1)-phosphotransferase) was purified from a crude extract of Kluyvera citrophila 627 (Enterobacteriaeceae) which has been grown on D-hamamelose. Ammonium-sulfate fractionation and twofold chromatography on DEAE-cellulose resulted in a 51-fold purification of the enzyme. Neither glucosekinase nor significant ATPase activity could be detected in the pure preparation. Besides D-hamamelose only D-hamamelitol was utilized as a substrate; however, the latter was phosphorylated at a very low rate. The molecular weight of the enzyme as estimated by gel chromatography is 21 000. The Km values for hamamelose and ATP were 3 mM nd 2.5 mM, respectively. The pH optimum was found at 7.5. In contrast to hexokinase, purified hamamelosekinase is very labile and could only be stabilized by addition of its substrate D-hamamelose. The most unusual property with respect to yeast hexokinase is a pronounced substrate inhibiton by hamamelose (> 5mM) and ATP (> 7mM), respectively, which could be interpreted as due to an economic utilization of the nutrient. Hamamelosekinase as well as glucosekinase are inducible by growing the microorganisms on the corresponding monosaccharides. PMID- 6249594 TI - Analysis of binding interactions between histone core complex and simian virus 40 DNA. A comparison of acetylated versus non-acetylated histone core complexes. AB - The interactions of acetylated and non-acetylated core complex histones with simian virus 40 (SV40) DNA 1 have been analyzed. A modified filter-binding assay utilizing micrococcal nuclease, which allows quantification of histone octamer binding to DNA has been developed. Using this assay it was determined that both non-acetylated core complex histones ad core complex histones acetylated with acetyl adenylate to levels existing in vivo bind cooperatively to SV40 DNA 1. Although both interactions are cooperative, the magnitude of the cooperativity parameter, omega, is significantly less in the acetylated case. This difference in cooperativity is in contrast to the nearly identical intrinsic association constant, K, observed in both cases. PMID- 6249595 TI - Chemically induced gene expression. Manipulation of the transforming ability of simian virus 40 minichromatin by specific chemical hyperacetylation of histones H3 and H4. AB - We have developed a non-enzymatic acetylating procedure, closely resembling the situation in vivo, utilizing acetyl adenylate, an acetylating agent in vivo, that mimics the enzymatic hyperacetylation of specific histone species. Analysis of the acetylated species of calf thymus histones produced from reaction with soluble chromatin yielded the same species generated in vivo and observed during active gene transcription. Four species of histone H4 and three of histone H3 occur with no alteration in histones H2A or H2B. This procedure has been utilized to hyperacetylate simian virus 40 (SV40) minichromatin in vitro in order to study the effect of acetylated compared to non-acetylated minichromatin in cellular transformation of cultured Balb/3T3 cells. Transformed cell foci appeared only in the cultures infected with hyperacetylated SV40 minichromatin. To select for cellular transformation, foci were transferred to agar-lined culture flasks and grown in the suspension of 1% methylcellulose. The selected cells were plated on slides and analyzed for the presence of T-antigen by indirect immunofluorescence. The hyperacetylated-minichromatin-infected cells exhibited T-antigen-specific fluorescence, while non-acetylated-minichromatin-treated cells and normal cells showed no specific fluorescence. These results suggest a major role for histone hyperacetylation in the mechanism of SV40 viral transformation. PMID- 6249596 TI - Glycogen synthase kinase-3 from rabbit skeletal muscle. Separation from cyclic AMP-dependent protein kinase and phosphorylase kinase. PMID- 6249597 TI - Cellular localization of the apurinic/apyrimidinic endodeoxyribonucleases in rat liver. AB - A method has been developed to purify rat liver nuclei; the isolated nuclei keep both nuclear membranes and retain more than 90% of the cell apurinic/apyrimidinic (AP) endodeoxyribonuclease activity. The nuclear enzyme is located mostly in chromatin non-histones; there is also an important amount of activity in the nuclear sap and some in the nuclear membranes. The cytoplasmic AP endodeoxyribonuclease activity is shared between mitochondria, cytosol and membranes. Different cell compartments appear to contain different AP endodeoxyribonuclease species: the membrane enzyme is activated by Triton whereas the other enzymes are rather inhibited; the nuclear sap enzyme has a higher molecular weight and a higher thermal resistance than the chromatin enzyme. A hypothesis is formulated according to which: (1) the chromatin enzyme is the only species important for nuclear DNA repair; (2) the species present in the other cell compartments might be precursors of the chromatin AP endodeoxyribonuclease. PMID- 6249598 TI - Generation of pyrophosphate from extracellular ATP at the surface of HeLa cells. AB - On incubation of intact HeLa cells with micromolar concentrations of [gamma 32 P]ATP under physiological conditions, the generation of inorganic pyrophophate in the supernatant has been observed. The reaction depends on incubation time and cell number employed; the enzymatic activity is not shed into the supernatant. Isotope dilution data support that the responsible enzyme(s) is located at the cell surface. PMID- 6249599 TI - 99mTc-colloid kits from the view point of the accretion in the bone marrow--with special reference to comparison with 198Au-colloid. AB - With 9 kinds of available 99mTc-colloid kits for RES imaging, especially from the aspect of RES imaging of the bone marrow, observations were conducted on pH, the presence of free 99mTcO4(-), labelling efficiency, rabbit blood clearance, the uptake in RES, urinary excretion, as well as the scintigraphy with rabbits and clinical cases. Compared to 198Au-colloid, marrow to liver ratio was found to be about the same, but its uptake to the spleen and liver was greater. In particular its urinary excretion was much more marked than 198Au-colloid, and in clinical use the bladder was more often delineated. This fact seems to suggest that it is desirable to develope a 99mTc-colloid more suitabale for the bone marrow scintigraphy. PMID- 6249600 TI - Radioiodocholesterol scintigraphy in adrenal gland tumors. PMID- 6249601 TI - Lymphomatoid granulomatosis manifesting as a subacute polyradiculoneuropathy. A case report and review of the neurological manifestations. PMID- 6249602 TI - Neuropathies associated with disorders of plasmocytes. AB - Neurological syndromes, e.g. polyneuropathies, can be associated with abnormal production of immunoglobulins, as for example in multiple myeloma. The pathogenetic mechanisms for the development of neurologic symptoms have often, indeed, remained obscure and speculative. This article presents some aspects of gammopathies correlated to polyneuropathy. Results of protein analyses of plasma and cerebrospinal fluid, utilizing a high separation technique, are presented. We also introduce a few case histories, illustrating the possible association between polyneuropathy and benign monoclonal gammopathy, hitherto regarded as an abnormality without clinical significance. The possible association between immunoiglobulin findings in cases of polyneuropathy with unknown etiology and a good response to steroid therapy is also mentioned. PMID- 6249603 TI - Lead polyneuropathy of nonindustrial origin. AB - A case of a subacute, distal, symmetrical polyneuropathy in a housewife is reported. The fact that the polyneuropathy affected almost only the motor fibers led us to suspect an exogenous intoxication. Blood lead level and the urinary excretion of lead after intravenous EDTA very high. The blood lead levels were normal in the husband and children oif the patient. A glazed cup used only by the patient to keep tea with lemon juice was found to release toxic amounts of lead with acidic solutions. The manufacturer of the cup was not identified by the enquiring authorities and therefore almost certainly other lead-releasing cups are still in use. The importance of suspecting lead intoxication in individuals not professionally exposed is stressed. PMID- 6249604 TI - Pure sensory polyneuropathy of herpes virus origin associated with meningoencephalitis. A case report. AB - A patient who had meningoencephalitis and corneal inflammation originating in a herpes virus infection sustained severe pure sensory polyneuropathy with superficial pain sensitivity and proprioceptive sensory deficits. The sensory deficiencies were diagnosed both in clinical and in electromyographic testings. The clinical EMG picture pointed to a pure sensory polyneuroplathy with a viral background according to blood serum and CSF examinations. PMID- 6249605 TI - Adrenomyeloneuropathy and adrenoleukodystrophy in two brothers. AB - A 19-year-old patient presented with spastic paraparesis and peripheral neuropathy without clinical or biochemical signs of adrenal insufficiency. The diagnosis of adrenomyeloneuropathy was supported by typical ultrastructural findings in peripheral nerve and endomysial nerve bundles and by a positive family history. Indeed his younger brother died at age 12 from a demyelinating disease of the central nervous system. Cutaneous nerve bundles and postmortem examination limited to the brain demonstrated features specific for adrenoleukodystrophy. The various features of both disorders are discussed. Their occurrence in the same sibship pleads strongly for a very close relationship. PMID- 6249606 TI - Adult metachromatic leukodystrophy. IV. Ultrastructural studies on the central and peripheral nervous system. AB - Ultrastructural studies on the central and peripheral nervous system of 2 patients with adult onset metachromatic leukodystrophy (MLD), dead at the ages of 46 and 51 years, showed MLD-specific inclusions, tufaceous and prismatic structures, a wide spectrum of membranous arrangements within lysosomal residual bodies, and the intimate admixture of sulfatides and other membranous material with lipopigments. Oligodendrocytes and Schwann cells were foremost affected but membranous inclusions could also be verified in neuronal perikarya and astrocytes. The varying ultrastructural spectrum of lysosomal residual bodies in adult onset MLD and the association with lipopigments, chiefly in nerve cells, exceed the fine structural observations on late infantile and juvenile MLD and may reflect morphological differences between these subtypes of MLD that are also known from clinical and biochemical observations. PMID- 6249607 TI - n-hexane polyneuropathy. An occupational disease of shoemakers. AB - The epidemiological, clinical, electrophysiological and nerve biopsy findings of 3 cases of n-hexane neuropathy in shoe industry are reported. The disease affects more than 1 person working in the same environment, regardless of their specific role, and occurs in factories where standards of hygiene are low. In the most severe cases the picture of peripheral neuropathy is associated with symptoms suggesting a concurrent involvement of the central nervous system such as dysarthria, disproportionate ataxia of the gait, blurred vision, and sometimes, after the recovery of the peripheral neuropathy, appearance of leg spasticity. Light- and electron microscopic study of peripheral nerve biopsies shows that the toxic produces a primary axonopathy characterized by segmental swellings of the fibers, due to accumulation of filaments. Retraction of the myelin from the node and segmental demyelination are secondary to the axonal changes. Experimental models of hexacarbon neurotoxicity may offer an explanation for the anatomical substrate underlying the symptoms related to the involvement of the central nervous system. PMID- 6249608 TI - Effects of cerebral gangliosides in the alcoholic polyneuropathies. AB - In chronic alcoholic patients with a slight or moderate polyneuropathy the effect of gangliosides at a daily dosage of 20 mg was investigated. A clinical improvement represented by a reappearance of the Achilles reflex and/or marked reduction of hypoaesthesia was found in the treated group. No significant changes in motor function were observed. No significant variation of the electrophysiological examination was found. PMID- 6249609 TI - Mouse mammary tumour virus-related antigens in core-like density fractions from large samples of women's milk. PMID- 6249610 TI - Changed Fc and C3 receptor pattern on human EBV-negative lymphoma cells, following in vitro conversion by EB-virus. PMID- 6249611 TI - Renin-angiotensin-aldosterone system. AB - There is increased activity of the renin, angiotensin, aldosterone (RAA) system in infancy and childhood. An inverse relationship between plasma renin, aldosterone and age has been demonstrated. In childhood hypertension due to renovascular disease or pyelonephritic scarring peripheral plasma renin is increased. Renal vein renin measurements in children with renal hypertension have proved valuable in predicting surgical curability of the underlying lesion. The upper limit of normal for the renal venous renin ratio in normotensive children without renal disease is 1.5. Pharmacological blockade of the RAA system has a place in diagnosis and treatment of hypertensive children. The plasma renin aldosterone profile is diagnostically useful in the investigation of salt-wasting disease and can easily distinguish between aldosterone biosynthetic defects and pseudohypoaldosteronism. PMID- 6249612 TI - The role of vesicular stomatitis virus major glycoprotein in determining the specificity of virus-specific and H-2-restricted cytolytic T cells. PMID- 6249613 TI - Mechanism of chlorpromazine action on plasma glucose and cyclic AMP levels. AB - The s.c. administration of chlorpromazine (CPZ) caused an elevation of plasma glucose and cyclic AMP levels in fed intact mice, but not in fed adrenalectomized mice. The pretreatment with reserpine partially blocked the elevation of plasma glucose and cyclic AMP. The pretreatment with 6-hydroxydopamine or alpha-methyl-p tyrosine failed to inhibit the increase of plasma glucose and cyclic AMP induced by CPZ. These findings suggest that CPZ acts on the central nervous system and increases plasma glucose and cyclic AMP through epinephrine release from the adrenal medulla. The elevations of plasma glucose and cyclic AMP induced by epinephrine were enhanced by CPZ. CPZ increased plasma glucose and cyclic AMP significantly at high room temperatures (28 and 33 degrees C) at which CPZ did not decrease body temperature. The mechanism of CPZ action is discussed in relation to the increase in the plasma glucose and cyclic AMP levels. PMID- 6249614 TI - Inhibition of neuronal uptake reduces the presynaptic effects of clonidine but not of alpha-methylnoradrenaline on the stimulation-evoked release of 3H noradrenaline from rat occipital cortex slices. AB - The iminoimidazolidine clonidine reduced concentration-dependently the release of 3H-noradrenaline evoked by electrical stimulation from the rate cerebral cortex. Exposure to the neuronal uptake inhibitors cocaine (10 micro M), desipramine (0.1 to 1 micro M) and amphetamine (1 micro M) significantly increased the stimulation evoked overflow of tritium. These uptake inhibitors antagonized the effects of clonidine on stimulation evoked 3H-noradrenaline release but failed to modify the inhibition induced by the catecholamine alpha-methylnoradrenaline. Inhibition of monoamine oxidase by preincubation of cerebral cortex slices with 0.5 mM pargyline significantly increased the stimulation-evoked overflow of tritium, but clonidine was as effective as in the controls in inhibiting 3H-noradrenaline overflow. The antagonism by desipramine of the clonidine-induced inhibition of neurotransmission could not be attributed to a blockade of presynaptic alpha adrenoceptors because: (1) the facilitating effect of phentolamine on 3H noradrenaline overflow was not modified in the presence of desipramine; (2) the magnitude of the inhibition of the stimulation-evoked 3H-noradrenaline release elicited by alpha-methylnoradrenaline was the same in the presence of cocaine or desipramine; (3) exposure to desipramine in the presence of cocaine did not further increase the stimulation-evoked release of 3H-transmitter. Since the catecholamine alpha-methylnoradrenaline inhibited neurotransmission in the presence of desipramine or cocaine, we can conclude that inhibition of neuronal uptake of noradrenaline antagonized selectively the presynaptic inhibitory effects of imidazolines on alpha 2-adrenoceptors. The influence of the inhibition of neuronal uptake on the presynaptic effects of imidazolines and catecholamines should be taken into account when the relative order of potencies of various alpha 2-adrenoceptors agonists is determined. PMID- 6249615 TI - 'gamma-MSH' fragments from ACTH-beta-LPH precursor have an affinity for opiate receptors. AB - gamma-Melanotropin (gamma-MSH), a putative peptide residing in the cryptic N terminal portion of ACTH-beta-LPH precursor, shares several amino acid residues with alpha-MSH or beta-MSH. The present study revealed that gamma-MSH and structurally related peptides had as potent an affinity for rat brain opiate receptors as did ACTH1-24 when 3H-naloxone was used as a ligand. Thus, gamma-MSH and structurally related peptides may have physiological significance in the activities of the CNS. PMID- 6249616 TI - Comparative study of analgesia induced by N VAL5- and Pro5-enkephalin analogs. AB - We have compared the analgesic potency of N-Val5 analogs and Pro5 derivatives in order to identify the mechanism of the unusually strong antinociceptive activity induced by Pro5 enkephalin analogs. Whereas N-Val5 and Pro5 compounds are equiactive in in vitro assays, N-Val5 derivatives are considerably less active analgesics than Pro5 analogs. Since N-Val is the homolog of Pro with an opened pyrrolidine ring, these data show that the cyclic structure of Pro participates in the strong in vivo activity of Pro5 analogs without altering the binding to the opiate receptor. PMID- 6249618 TI - Pentobarbital potentiates GABA-enhanced [3H]-diazepam binding to benzodiazepine receptors. PMID- 6249617 TI - Antagonism of an indirectly acting agonist: block by propranolol and sotalol of the action of tyramine on rat heart. AB - Some agonists act indirectly in the sense that they cause the release of a second substance that brings about the response finally observed. An antagonist which competitively inhibits the action of the intermediate substance will also reduce the response to the indirectly acting agonist, provided that the receptors are freely accessible. A simple mass-law model for indirect antagonism of this kind is presented, and its predictions are compared with the results obtained in an experimental study of the influence of propranolol and sotalol on the inotropic response of isolated rat atria to tyramine. While there is reasonable qualitative agreement, the fit is not exact and reasons for this are discussed. PMID- 6249619 TI - The regulation of cardiac muscarinic cholinergic receptors by isoproterenol. PMID- 6249620 TI - The effects of long-term ethanol on brain receptors for dopamine, acetylcholine, serotonin and noradrenaline. AB - Rats were treated with ethanol for 11-15 days, after which the brain neurotransmitter receptors for dopamine, acetylcholine, serotonin and noradrenaline were measured. The rats were intubated at 12 h intervals with 4 g/kg ethanol, and sacrificed 10 h after the last intubation. After ethanol treatment, the specific binding of 3H-haloperidol to dopamine receptors was significantly decreased in the mesolimbic areas by 20 +/- 6%, but was unchanged in the striatum. Specific binding of 3H-serotonin was increased by 63 +/- 29% in the striatum and by 32 +/- 9% in the brainstem, but decreased by 20 +/- 7% in the hippocampus. The specific binding of 3H-quinuclidinyl benzilate to muscarinic acetylcholine receptors increased by 7 +/- 2% in the striatum, but decreased by 5 +/- 2% in the cerebral cortex. The specific binding of 3H-WB-4101 to alpha adrenergic receptors was unchanged in all brain areas assayed, namely the striatum, mesolimbic areas, hippocampus, hypothalamus, brainstem and cerebral cortex. These changes may be related to some aspects of tolerance to, and dependence on, ethanol. PMID- 6249621 TI - Effects of chronic administration of delta 9-tetrahydrocannabinol on the cardiovascular system, and pressor and behavioral responses to brain stimulation in freely moving rats. AB - The effects of chronic administration of delta 9-THC on the cardiovascular system, and the pressor and behavioral responses to brain stimulation were investigated in freely moving rats with chronic electrode and arterial cannula implants. delta 9-THC at a dose of 6 mg/kg was injected intraperitoneally once a day for 10 days through an abdominal cannula. On the first day, delta 9-THC induced a significant decrease in heart rate and rise in blood pressure. The animals exhibited abnormal behavior such as catalepsy, walking backward and pivoting. On the 5th day, the bradycardia induced by delta 9-THC markedly decreased and on the 10th day tachycardia was observed. The pressor effect of delta 9-THC significantly increased on the 5th and 10th days. However, delta 9 THC-induced abnormal behavior was observed without any changes following chronic administration. delta 9-THC inhibited the pressor response and behavioral changes to electrical stimulation of the posterior hypothalamus and midbrain reticular formation. No tolerance developed to these depressive effects of delta 9-THC after chronic treatment. These data suggest that tolerance develops only to bradycardic effect of delta 9-THC and that the decrease in vagal activity may play some role in the development of tolerance. PMID- 6249623 TI - Rapid development of tolerance to the hyperthermic effect of beta-endorphin, and cross-tolerance between the enkephalins and beta-endorphin. PMID- 6249622 TI - Sedative and analgesic actions of methoxylated 2-aminotetralins; involvement of alpha 1- and alpha 2-adrenoreceptors. AB - Three 5,8-dimethoxylated derivatives of 2-aminotetralin (2-AT) were compared with clonidine, methoxamine and phenylephrine in tests for sedation (inhibition of exploratory activity) and analgesia. In both tests the 2-AT derivatives were less potent than clonidine, but more potent than methoxamine or phenylephrine. Antagonism of the 2-AT derivative, DR-31, and clonidine by yohimbine in both tests argues for the involvement of alpha 2-adrenoreceptors in the mediation of these behavioral effects. alpha 1-Adrenoreceptors may also mediate an inhibition of exploratory activity since the inhibition induced by methoxamine was antagonized by phenoxybenzamine (POB) but not by yohimbine. The methoxylated 2-AT derivatives, which have previously been shown to exert potent peripheral alpha 1 agonism are now demonstrated to have sedative and analgesic effects characteristic of central alpha 2-adrenergic stimulation. PMID- 6249624 TI - Effect of azepexole (B-HT 933) on pre- and postsynaptic alpha-adrenoceptors at peripheral and central nervous sites. PMID- 6249625 TI - Effects of prazosin on the cAMP system in the spontaneously hypertensive rat (SHR) aorta. AB - 3',5'-adenosine monophosphate (cAMP), adenylate cyclase and cAMP phosphodiesterase (PDE) activity were measured in aorta homogenates from normal and spontaneously hypertensive rats (SHR) during treatment with prazosin, an antihypertensive drug. cAMP levels were lower in SHR than in normal rats. In SHR prazosin treatment induced marked inhibition of PDE activity thus causing an increase in cAMP levels; adenylate cyclase activity remained unaffected. This effect was only present for the first 32 days of drug administration. PMID- 6249626 TI - Anticonvulsant effects of careulein and cholecystokinin octapeptide, compared with those of diazepam. AB - Caerulein and the C-terminal octapeptide of cholecystokinin (CCK-8), after subcutaneous administration to mice, both delayed the onset and retarded the development of toxic effects of convulsants such as strychnine, pentetrazol, bicuculline, and picrotoxin. They also increased the seizure threshold doses of intravenously infused pentetrazol and picrotoxin. In this regard, both peptides were at least equipotent with diazepam. PMID- 6249627 TI - Pituitary cell cultures contain muscarinic receptors. AB - The presence of muscarinic receptors in 5-day dissociated cell cultures of rat anterior pituitary glands was detected by atropine-sensitive binding of 3H quinuclidinyl benzilate (3H-QNB). Muscarinic receptor levels in cultures were compared to levels of receptors for dopamine and thyrotropin releasing hormone. PMID- 6249628 TI - Effect of some antiarrhythmics on [3H]clonidine binding to alpha 2-adrenergic receptors. AB - The effects of the antiarrhythmics quinidine, propranolol, procainamide and lidocaine were determined on the specific binding of [3H]clonidine to the alpha 2 adrenergic receptor. Quinidine is effective in decreasing specific [3H]clonidine binding to the alpha 2 receptor within the range of therapeutic blood levels (Ki = 6 x 10 (-8) M). The effectiveness of all compounds tested, with the exception of quinidine and procainamide, correlate with the membrane/buffer partition coefficient, suggesting a relationship with the local anesthetic activity. PMID- 6249629 TI - Angiotensin I converting enzyme (kininase II) in ocular tissues. PMID- 6249630 TI - Facilitation and inhibition of jaw reflexes evoked by electrical stimulation of the cat's cerebral cortex. AB - The effects of electrical stimulation of the cerebral cortex on the monosynaptic jaw closing and the disynaptic jaw opening reflexes were studied in cats anaesthetized with chloralose. The time course of the reflex effects was recorded. Similar rhythmic sequences of facilitation and inhibition were observed in both reflexes (Fig. 3). The sequence could start with facilitation or inhibition. The latency of the initial effects was short (2.5 ms) indicating a minimum of two synapses in the descending path. The period of the rhythmic sequence was approximately 10 ms. Optimal parameters for the conditioning cortisol stimuli were found to be: trains of 3-5 surface anodal pulses, 0.5 ms, 400 Hz. The threshold of the cortical effects on the reflexes was 0.3 mA. A single pulse evoked effects. The cortical origin of the effects was located and related to the somatosensory projections, and to the cytoarchitecture. The effects of largest amplitude and most complex time course were evoked from the oral and perioral projections to areas 3a and 3b. Effects evoked from areas 4 gamma, 5a, and 6a beta were less complex and of lower amplitude. It is suggested that a trigemino-cortico-trigeminal loop via 3a may function in reflex modulation of the jaw movements. In addition area 3a may contribute to cortico-cortical motor elaborations via U-fiber connections to area 4 gamma. PMID- 6249631 TI - Slow waves and unitary activity evoked by cutaneous stimulation from the rat cuneate nucleus. AB - Depth profiles of averaged evoked potentials (AEPs) and simultaneously generated unitary activity have been recorded from the cuneate nucleus of the rat in response to controlled tactile stimulation of the ipsilateral forepaw. Four separate components of the AEPs were isolated, N1, N2, P, and N3. N1 corresponds to the classical N wave previously described by other workers; four fractions of N1 are described. The classical P wave which follows N1 reverses at 150--350 micrometers depth to become a negative wave of identical time course, the N2 wave, at deeper locations. N2 peaks deeper than N1 within the non-relay portion of the cuneate nucleus, or below in the subnuclear reticular formation where it is the only significant evoked component. Its strong susceptibility to high Mg++ C.S.F. superperfusion suggests a polysynaptic origin. It is argued that the depth distribution and time course of N2 does not support its function relating to depolarisation of primary afferents (PAD) in the vicinity of synaptically driven cuneate cells. Alternative possibilities for its origin are discussed. An additional sustained component of the AEP, the N3 component, is described and evaluated. N3 is co-extensive with N1, has a long time course and simple exponential decay, and is the component most resistant to high Mg++ C.S.F. superperfusion. A similar component to N3 has been described by previous workers in the spinal cord, where it has been shown to arise from glia depolarised by K+ effluxing from discharging afferents and cells. A similar origin for N3 is suggested, and its possible involvement with PAD discussed. PMID- 6249632 TI - Histologic, immunocytologic and subcellular changes in the rat adenohypophysis caused by prolactin, growth hormone and ACTH-producing transplanted pituitary tumors: a comparison with spontaneous prolactin-producing adenomas. PMID- 6249633 TI - Manganese induced testicular changes in monkeys. AB - Oral administration of manganese chloride (25 mg/kg b. w. daily) to monkeys for a period of 18 months produced congestion and marked increase in weight of testis. Histopathologic examination revealed interstitial oedema and degeneration of seminiferous tubules. Activities of succinic dehydrogenase, glucose-6-phosphate dehydrogenase and acid phosphatase were significantly inhibited whereas NADH diaphorase and alkaline phosphatase activities showed only slight inhibition in seminiferous tubules of treated monkeys. It was concluded that chronic exposure to manganese does not produce sever degenerative changes in the testis earlier than metal induced encephalopathy in primates. PMID- 6249634 TI - The response of cyclic 3',5'-AMP and cyclic 3',5'-GMP phosphodiesterases to experimental diabetes. AB - Alloxan diabetes caused a decrease in cyclic AMP phosphodiesterase in all affected rat tissues. Cyclic GMP phosphodiesterase activity was, however, decreased in adipose and liver, but increased increased in heart and uterus. PMID- 6249635 TI - Satellite DNA sequences and reproductive isolation in the Drosophila willistoni group. PMID- 6249637 TI - Inhibition of the oxidant--induced reduction of cytochrome b by a synthetic analogue of ubiquinone. PMID- 6249636 TI - Effects of inhibition and stimulation of Na+-K+ active transport on the resting membrane input conductance of the guinea-pig ventricle. AB - The effects of inhibition by ouabain and stimulation by high frequency drive of the sarcolemmal Na+-K+ active transport system on the resting input conductance (gi) of guinea-pig ventricular muscles were determined. Although both pump inhibition and stimulation were associated with changes in electrophysiological properties of the muscles, neither had a significant effect on gi. PMID- 6249638 TI - Selective spin labeling of sialic acid residues of glycoproteins and glycolipids in erythrocyte membranes: a novel method to study cell surface interactions. PMID- 6249639 TI - Opposite effects of dibutyryl cyclic GMP and dibutyryl cyclic AMP on glucose 1,6 diphosphate levels and the activities of glucose 1,6-diphosphate phosphatase and phosphofructokinase in diaphragm muscle. PMID- 6249640 TI - Calcium movements in in situ mitochondria following activation of alpha adrenergic receptors in rat liver cells. PMID- 6249641 TI - Phage lambda integration protein: synthesis in lambda-infected minicells and membrane affinity. PMID- 6249642 TI - Soluble and membrane-bound paramagnetic centers in methanobacterium bryantii. PMID- 6249643 TI - The estimation of protein secondary structure by laser Raman. Spectroscopy from the amide III' intensity distribution. PMID- 6249644 TI - Quantitative evaluation of electrophoretic allo-and isozyme patterns. PMID- 6249645 TI - The meaning of tissue pO2 and local blood flow for the chemoreceptive process of the carotid body. AB - The paper concentrates on measurements of tissue pO2 and local flow, which are both assumed to determine the nervous signal of the carotid body. The measurements were performed with needle electrodes. Inside the specific tissue of the carotid bodies of cat and rabbit, which is assumed to be surrounded by an oxygen barrier, pO2 values between 7 and 25 torr were recorded. From experiments on the fetal carotid body it was concluded that these low values are essential for the chemoreceptive process. Two types of blood flow were observed in the carotid body: high flow running through arteriovenous shunt vessels or flow through channels (total flow), and low flow running through the capillaries supplying the specific tissue (local flow). Local flow decreases under hypoxia, whereas total flow follows the changes in blood pressure in any case. These pO2 dependent regulatory mechanisms influence the extracellular calcium activity, which determines the calcium uptake of type I cells under hypoxia and, consequently, (by vesicle release) the chemoreceptor discharge. Other mechanisms are assumed to be involved during hypercapnia, since under these conditions local flow does not change. PMID- 6249646 TI - Physiological and experimental regulation of taurine content in the heart. AB - High concentrations of taurine are found in the heart and these are increased still further in congestive heart failure. It appears that taurine is largely derived by influx from the circulation, and this influx is stimulated by cyclic AMP, whereas influx of alpha-amino acids is unaffected. Influx occurs via a saturable transport system that has strict requirements for ligands. Other substances are transported by this system, including beta-alanine, hypotaurine, guanidoethyl sulfonate, and, to a lesser extent, guanidinopropionate; and these are competitive antagonists for taurine transport. Guanidinoethyl sulfonate, in vivo, markedly lowers taurine concentrations over the course of a few days in all tissues examined in the rat and mouse (but not in the guinea pig). The concentrations of other amino acids are unaffected. Guanidinoethyl sulfonate may prove to be a useful substance in the study of the biological role of taurine, in view of its ability to regulate taurine content in a number of species. Despite the numerous pharmacological actions of taurine, its physiological function in the heart remains problematic. One function appears to be the modulation of calcium movements. The inotropic actions of taurine and beta-adrenergic activation may be linked via the cyclic AMP-dependent regulation of taurine influx. PMID- 6249647 TI - Partial adrenocortical hydroxylase deficiency syndrome in infertile women. PMID- 6249648 TI - [Electrophysiologic analysis of the action of a series of anticholinesterase agents on the functional state of peripheral nerves and neuromuscular transmission in warm-blooded animals]. PMID- 6249649 TI - [Effect of purified erythrocyte chalone on proliferating cells of the mouse erythron]. PMID- 6249650 TI - [Changes in cell membrane excitability during guinea pig papillary muscle after contractions]. AB - In isolated guinea-pig papillary muscles, the excitability of cellular membrane was investigated during the after contractions induced by cooling of the perfusate to 13--15 degrees C, addition of noradrenaline (2 mg/l), and calcium to 16 MM. At stimulation rate 0.2 Hz the oscillation amplitude was 19 +/- 2% of the initial contraction. The activity of the fast sodium channels was estimated by the threshold for AP initiation and appeared to increase gradually after the end of AP. Slow channel response measured in the high potassium solution (29 MM), significantly decreased during the after contraction. Even at supramaximal amplitude of stimulation the slow responses were about 10--20 mV smaller than those after or before oscillation. Slow channel activity seems to depend on intracellular calcium concentration. Oscillations after contractions were abolished by addition of caffeine (2 mM). The oscillations seem to result from recirculation of calcium between myoplasma and sarcoplasmatic reticulum. PMID- 6249651 TI - [Role of fast Na--Ca current channels in effecting parathyroid hormone action]. AB - Under conditions of incomplete tetrodotoxin (TTX) blockade of the fast channels, the parathyroid hormone augmented the AP amplitude, accelerated development of ascending depolarization, and enhanced the AP plateau in the frog myocardium cells. The TTX appears to activate Ca++ transport both in the slow and fast Ca++- Na+ channels which participate in formation of the AP slow phase of ascending depolarization in the frog myocardium cells. PMID- 6249652 TI - [Role of cholinergic mechanisms in development of the rhythmic activity of motoneurons of the amphibian lymphatic center]. PMID- 6249653 TI - Vitamin D deficiency rickets. PMID- 6249654 TI - [The black hidrocystoma (Monfort)]. PMID- 6249655 TI - Animal model for small cell carcinoma of the lung. Effect of immunosuppression and sex of mouse on tumor growth in nude athymic mice. AB - An animal model for the experimental study of small cell carcinoma of the lung (SCCL; human) has been developed. Tumors arising from continuous cell lines of cultured tumor cells as well as transplantable tumors of human SCCL in nude athymic mice have been characterized as to growth rate and morphology. The effect of antilymphocyte and antithymocyte sera and the sex of the host mouse were evaluated. PMID- 6249656 TI - Regulation of renal gluconeogenesis by alpha-adrenergic action. PMID- 6249658 TI - Energetics and specificity of transcellular NaCl transport in the dog kidney. PMID- 6249659 TI - Energetics of active transtubular transport; function of the Na-K-ion pump. PMID- 6249657 TI - Insulin receptors of isolated glomeruli. PMID- 6249660 TI - Structure, function and regulation of Na-K-ATPase. PMID- 6249661 TI - Operation of the renal Na+ -K+-pump in artificial membranes. PMID- 6249662 TI - Indications of several nucleotide binding sites on the Na+ -K+-ATPase molecule. PMID- 6249663 TI - Use of mono- and bifunctional group-specific reagents in the study of the renal Na+ -K+-ATPase. PMID- 6249664 TI - Diversity of effects of fructose loads on different parts of the nephron. PMID- 6249665 TI - Microdetermination of Na-K-ATPase in single tubules: its application for the localization of physiologic processes in the nephron. PMID- 6249666 TI - Effect of bicarbonate on glutamine metabolism. PMID- 6249667 TI - The sodium ion/calcium ion cycle of cardiac mitochondria. PMID- 6249668 TI - Evidence for the existence of a histidine residue at the active site of the nuclear-envelope enzyme involved in nucleo--cytoplasmic RNA transport in mammalian liver [proceedings]. PMID- 6249669 TI - Location of cytochrome bc1 complex in mitochondrial inner membrane [proceedings]. PMID- 6249670 TI - Stimulation of rat liver initiation factor eIF-2 by a factor with guanosine diphosphase activity [proceedings]. PMID- 6249671 TI - Lipolytic agents as regulators of fatty acid esterification in rat adipose tissue [proceedings]. PMID- 6249672 TI - Xanthine oxidase in adipose tissue: potential effects on lipolytic activity [proceedings]. PMID- 6249673 TI - The mechanism and function of phosphatidylinositol turnover [proceedings]. PMID- 6249674 TI - Selective inhibition of rat lung cyclic AMP phosphodiesterase and cyclic GMP phosphodiesterase by cyclic nucleotides and their analogues and various drugs [proceedings]. PMID- 6249675 TI - The effect of insulin and adrenaline on the phosphorylation of a 22 000-molecular weight protein within isolated fat cells; possible identification as the inhibitor-1 of the 'general phosphatase' [proceedings]. PMID- 6249676 TI - The permissive action of glucocorticoid on the inhibition of hepatic lipogenesis by glucagon in the rat [proceedings]. PMID- 6249677 TI - Studies on the purification of glucose 6-phosphatase from rabbit liver microsomal fraction [proceedings]. PMID- 6249678 TI - Genetics of restriction/modification systems. PMID- 6249679 TI - Adenosine triphosphate-requiring restriction enzymes. PMID- 6249680 TI - Restriction endonucleases and their recognition sequences. PMID- 6249681 TI - Sequence determination of restriction-endonuclease recognition sites. PMID- 6249682 TI - The specificity of the EcoRI restriction endonuclease. PMID- 6249683 TI - Induction of neural-like cells and acetylcholinesterase activity in cultures of F9 teratocarcinoma treated with retinoic acid and dibutyryl cyclic adenosine monophosphate. PMID- 6249684 TI - Calcium efflux during germination of Blastocladiella emersonii. PMID- 6249685 TI - Partial sequence analysis of Xenopus alpha- and beta-globin mRNA as determined from recombinant DNA plasmids. PMID- 6249686 TI - Comparative properties of the in ovo and in vitro differentiation of the muscarinic cholinergic receptor in embryonic heart cells. PMID- 6249687 TI - Free calcium changes associated with hormone action in amphibian oocytes. PMID- 6249688 TI - Glucosamine metabolism in Drosophilia virilis salivary glands: ontogenetic changes of enzyme activities and metabolite synthesis. PMID- 6249689 TI - Variability in derivative strains of Bordetella pertussis. AB - Bordetella pertussis strain UT25 was isolated on Bordet-Gengou(B-G) agar from a child with whooping cough in 1977. Derivative strains were isolated from UT25 by serial passages on Trypticase Soy Agar (TSA) containing blood,followed by serial passages on plain TSA. At passage 69, UT25 was subcultured in parallel on TSA and B-G. For experiments, strains were grown in defined liquid medium, adjusted to a standard turbidity, and tested in parallel. Tests were performed to detect changes in immunogenicity, production of dermonecrotic toxin, histamine sensitizing ability, serologic properties, infectivity for mice by the intranasl route, production of adenylate cyclase, patterns of outer membrane proteins. Notable changes occurred in the properties of UT25 at passage 16, just when stable growth on blood-fresh medium was established. After 5 additional passages on TSA, however, the strain resembled the original isolate. At about passage 45, biological activity began to decline, and by passage 60 most biological activities were sharply diminished or undetectable. No recovery of biological activity was observed during a further 15 passages on TSA. Strains derived from the sixty-ninth passage of UT25, after passage on B-G for 5 subcultures, showed partial recovery of biological activity. Ten additional subcultures on B-G yielded strains which showed even higher biological activity. Fluorescent antibody staining confirmed that all strains studied were B. pertussis, and maintained reactive surface antigen(s), in spite of loss of agglutinability in specific antiserum. PMID- 6249690 TI - Detection of primate herpesvirus antibodies including Herpesvirus simiae by enzyme immunoassay. AB - An enzyme immunoassay (EIA) was used for the detection of antibodies to Herpesvirus hominis type 1 and 2 (HVH-1 and HVH-2), SA8 and Herpesvirus simiae (HVB) in human and nonhuman primate sera. Optimal assay conditions were approximately the same for HVH-1, HVH-2, and SA8 but different for HVB. The recognized lethality of HVB required studies to determine whether or not inactivated HVB could be used in the EIA outside a biohazard safety cabinet. Ten percent buffered formalin destroyed infectivity of antigen coated discs after 5 minutes while retaining activity in the EIA. Antibody titers to HVB determined by serum neutralization were up to eightfold higher in the EIA. Using EIA to survey sera for antibodies to herpesviruses, it was determined that most humans reacted to HVH-1 (88%), HVH-2 (81%) and SA8 (94%), and 38% to HVB. Whereas baboons reacted almost exclusively to their indigenous herpesvirus SA8 (44%), rhesus monkeys demonstrated a high positive rate to HVH-1 (63%), SA8 (94%), and HVB (50%). These data indicate that EIA is rapid, sensitive, reproducible, and useful in the detection of antibodies to human and nonhuman primate herpesviruses but does not, at this point, resolve problems related to cross-reactivity among these viruses. PMID- 6249692 TI - Regulation of hepatic sodium plus potassium-activated adenossine triphosphatase activity by glucocorticoids in the rat. PMID- 6249691 TI - Impaired T cell function and decreased natural killer activity in patients with liver cirrhosis and their significance in the development of hepatocellular carcinoma. AB - It is well known that the incidence of hepatocellular carcinoma (HCC) in patients with liver cirrhosis (LC) is very high. We investigated the immunological state in patients with LC and HCC. T cell population of peripheral blood lymphocytes (PBL) and blast transformation of PBL by phytohaemagglutinin (PHA) were significantly decreased in patients with LC. Natural killer activity against HeLa cell was also significantly decreased in these patients. These results suggest that immunological surveillance is impaired in patients with LC and this may be one of the aetiological factors in genesis of hepatocellular carcinoma in patients with LC. PMID- 6249693 TI - Alteration of rat liver plasma membrane fluidity and ATPase activity by chlorpromazine hydrochloride and its metabolites. PMID- 6249694 TI - Dog intestinal mucosa contains two vitamin D-stimulating calcium binding proteins. AB - Dog intestinal mucosa has been found to contain more than one vitamin D responsive calcium-binding protein (CaBP). Duodenal and upper jejunal mucosa contains a protein that has a mol wt of 19,000 and a Kd of 1.2 microM, and that increases in activity over twofold after administration of 1,25 (OH)2 vitamin D3. This protein could not be demonstrated in ileal tissue. In ileal mucosa all the calcium binding activity resides in fractions that elute from Sephadex G200 with a mol wt of about 57,000. Calcium-binding activity was demonstrated in gel electrophoresis corresponding to a protein with an Rf of about 0.5, unlike the small CaBP, which has an Rf of 1.0. The calcium-binding activity from the ileum was demonstrated to coincide with a protein band on acrylamide gel electrophoresis, and to be destroyed by pronase. This large CaBP responded to 1,25 (OH02 vitamin D3 by increasing activity by about 50%, and was inhibited similarly to the small protein by Sr, Ba, and Mg. Neither fresh tissue homogenates, nor explants cultured up to 20 hr showed any evidence of the small CaBP on disc gel acrylamide electrophoresis. The small CaBP could be demonstrated on gel electrophoresis only in tissue that was partially autolyzed or was treated with a 10% (milligrams per milligram) solution of trypsin. The small CaBP was relatively resistant to trypsin. It is suggested that the small CaBP may be derived at least in part from the large protein. PMID- 6249695 TI - General anaesthetic action in the invertebrate central nervous system. PMID- 6249696 TI - Na+-independent binding of [3H]GABA and [3H]muscimol to a "microsomal" fraction, but not to a myelin fraction of rat brain; further evidence that glial elements do not possess GABA-receptors. PMID- 6249697 TI - Pre- and postjunctional potentiation of the adrenergic neurotransmission by angiotensin II in the perfused rabbit kidney. PMID- 6249698 TI - Humoral-and cell-mediated immune responses to herpesvirus antigens in patients with cervical carcinoma. PMID- 6249699 TI - Pretreatment curettage-A predictor of chemotherapy response in gestational trophoblastic neoplasia. PMID- 6249700 TI - Human chorionic gonadotropin-secreting large cell carcinoma of the lung detected during follow-up of a patient previously treated for gestational trophoblastic disease. PMID- 6249701 TI - [Aging of the nervous system and control mechanisms]. PMID- 6249702 TI - [Pharmacological studies of new sulfhydryl compounds 2-mercapto-2-methylpropanoyl L-cysteine (SA96). I. Evaluation of anti-rheumatic action (author's transl)]. AB - Oral administration of 2-mercapto-2-methylpropanoyl-L-cysteine (SA 96), a newly synthesized sulfhydryl compound, showed protective and curative effects on adjuvant-induced arthritis in rats similarly to those seen with D-penicillamine (D-PA). However, the effects of these compounds were not dose-dependent, and the maximum effects of SA96 were observed at 10 mg/kg/day. On the contrary, SA96 and D-PA had little effect on the various acute and subacute inflammatory responses induced in rat and mice. Formation of hemolytic plaque forming cells in the spleen of mice immunized with 5 X 10(8) sheep red blood cells was potentiated by the oral administration of both compounds. These stimulatory effects of SA96 and D-PA on the humoral immune responses were also not dose-dependent, and the maximum effects of SA96 were observed with 10 mg/kg/day, as in the case of adjuvant-induced arthritis in rats. In in vitro experiments, the inactivation of rheumatoid factor and the inhibition of collagenase and bone alkaline phosphatase activities were observed with both compounds, but these effects of SA96 were more potent than those of D-PA. As there is a similarity in the pharmacological profiles of SA96 and D-PA, SA96 may prove to be clinically effective for rheumatoid arthritis. PMID- 6249703 TI - Simultaneous induction of three catabolic enzymes in Escherichia coli. AB - During a simultaneous induction of three enzymes which are subject to catabolite repression (beta-galactosidase, tryptophanase and amylomaltase, or beta galactosidase, tryptophanase and D-serine deaminase) in a batch culture, the rates of synthesis of beta-galactosidase and tryptophanase decreases, while the rates of synthesis of amylomaltase and D-serine deaminase remain unaffected. The addition of cAMP brings about a considerable increase of the rate of synthesis of D-serine deaminase and a partial synthesis rate increase of beta-galactosidase whihle the synthesis rate of tryptophanase remains lowered and the synthesis rate of amylomaltase remains unaffected. In a continuous culture beta-galactosidase, tryptophanase and D-serine deaminase are synthesized simultaneously at a maximum rate without mutual influence. The addition of cAMP increases the rate of synthesis of all three enzymes. PMID- 6249704 TI - Enzyme apparatus of the genus Fusarium. AB - The ability to degrade oligo- and polysaccharides by enzymes of the glycosidase and glucan-glucan hydrolyse type, and esterase, phosphatase, proteinase, peroxidase, catalase, laccase and tyrosinase activities were tested in 35 strains of 11 sections of the genus Fusarium. PMID- 6249705 TI - Isolation of intact plankton from drowning lung tissue by centrifugation ina colloidal silica gradient. AB - Several species of intact phyto- and zooplankton from the homogenate of rat "drowning lung" were separated by centrifugation in a colloidal silica gradient. The plankton, except diatoms, were isolated from a small amount of human "drowning lung" by this procedure. This new method was found to be more useful in detecting plankton in tissues than chemical digestion with strong acid. PMID- 6249706 TI - Role of carbohydrates in thyrotropin binding sites. AB - The role of carbohydrates in thyrotropin binding was studied by glycosidase treatment of human thyroid membranes. Removal of over 75% of membrane sialic acid resulted in a 50% increase of TSH binding, measured in 10 mM Tris-HCl, 50 mM NaCl, 0.1% bSA, pH 7.4, 37 degrees C (buffer A). This augmentation was due to an increase in binding to high affinity sites (Ka 1 X 10(10)M-1). The binding was highly specific and was not significantly inhibited by gangliosides. In contrast, low affinity binding of TSH was unchanged either in buffer A or in 10 mM Tris acetate, 0.1% bSA pH 6.0, 4 degrees C (buffer B) and was inhibited by gangliosides. Treatment of membranes with beta-galactosidase, beta-N acetylglucosaminidase and alpha-L-fucosidase had little effect on TSH binding. The data suggests that membrane-associated sialic acid inhibits TSH binding to high affinity receptors and that gangliosides are not involved in tthis TSH receptor interaction. PMID- 6249707 TI - Ontogeny of opiate receptor sites in brain: apparent lack of low affinity sites during early neonatal life. PMID- 6249708 TI - Thyroid hormone regulation of central nervous system (CNS) beta-endorphin and ACTH. PMID- 6249709 TI - A radioimmunoassay for pregnancy associated protein, beta 1SP1: levels in pregnancy, trophoblastic and neoplastic disease. AB - A radioimmunoassay system for the glycoprotein beta 1SP1, one of the pregnancy associated proteins, has been set up. beta 1SP1 levels in normal pregnancy have been established transversally. Clearance (t1/2) from the circulation postpartum ranged from 1.4 to 1.8 days. Several patients with trophoblastic disease, e.g., mola hydatidosa, choriocarcinoma and embryonic cell carcinoma, were followed longitudinally. Human chorionic gonadotropin (hCG), a highly reliable tumor marker in trophoblastic disease, has been determined concomitantly by radioimmunoassay. In all instances, hCG proved to be a better indicator of the presence of a tumor, because by the time beta 1SP1 became undetectable, hCG could still be detected. Samples from a large multicenter study on trophoblastic disease were studied: out of 100 positive for hCG, beta 1SP1 could be detected in 86; however, out of 21 samples in which hCG was not detectable, 1 was found to be positive for beta 1SP1. In a number of samples from patients with bronchial carcinoma, no beta 1SP1 could be detected. PMID- 6249710 TI - Treatment in the seventies: a decade of refinement. AB - In the treatment of mental disorders, the 1970s was a decade of increasing refinement and specificity of existing treatments. There was increasing focus on the negative effects of various treatments, such as deinstitutionalization, and a stronger scientific basis for some treatments emerged. For instance, the field of somatic treatments saw a greater and more sophisticated use of lithium, accompanied by concern about possible side-effects of goiter and renal changes; greater specificity of the anti-depressants; more widespread monitoring of plasma levels; and growing attention to the tardive dyskinesias. In psychotherapy there was a change toward more eclectic and pragmatic approaches, as evidenced by the combining of behavioral and dynamic techniques and an increased use of short-term psychotherapies, plus a concern with efficacy. Ties between the mental health care and general health care fields became stronger, as evidenced by the growth of consultation-liaison programs, the often combined delivery of mental and physical health services, and advances in behavioral medicine. The authors expect such trends to continue in the 1980s, along with a greater rigor in diagnostic systems and an increased focus on prevention. PMID- 6249711 TI - The effect of referral procedures on aftercare compliance. AB - A study of four referral procedures involving 400 patients discharged consecutively from a geographically distant state hospital and referred to a community mental health center for aftercare suggests that simple changes in hospital discharge systems can increase compliance of patients and reduce recidivism. The scheduling of a specific follow-up appointment for the patient increased aftercare compliance significantly. Compliance was further increased, and the recidivism rate was cut in half, when the patient was seen by the community mental health aftercare nurse before discharge and was also given a specific follow-up appointment with that nurse. PMID- 6249712 TI - The vitamin d hormonal system: implications for bone diseases. AB - A half century ago, vitamin D was recognized as a vitamin. Now it has become clear that it is also a hormone--indeed the biochemical cornerstone of a major hormonal system involved in regulating the body's calcium economy. The active metabolite, calcitriol, produced in the kidney, acts on bone and intestine and has been found effective in therapy of osteodystrophy and perhaps other metabolic bone diseases. PMID- 6249713 TI - The problems of poliovirus immunization. PMID- 6249714 TI - Sclerosing vascular variant of plasma cell granuloma. AB - A single mass in the right lung was found in a 33 year old asymptomatic male by routine chest x-ray examination. In the surgically removed right middle lobe was a well circumscribed but nonencapsulated round tumor (diameter, about 4 cm.) compressing and gradually becoming incorporated into the adjacent pulmonary parenchyma. Histologically the bulk of the tumor consisted of numerous hyalinized blood vessels in a loose mesenchymal background, the latter containing spindle shaped connective tissue cells and an acid mucopolysaccharide stroma. At the margins in the fibrous septa, which divided the tumor into nodules, there was intense lymphoplasmacytic infiltrates forming lymphoid follicles. No epithelial elements were observed around the hyalinized blood vessels. Electron microscopic findings suggest mesenchymal cells, giving rise to endothelial cells of numerous blood vessels and spindle cell connective tissue cells associated with unique lymphoplasmacytic aggregates. The unusual tumor best fits the characteristics of the sclerosing plasma cell granuloma, composed predominantly of sclerosing vascular vessels. PMID- 6249715 TI - Ultrastructure of nuclear "inclusions" in pheochromocytoma and paraganglioma. AB - Nuclear "inclusions" similar to those seen in a variety of normal and neoplastic cells are commonly found in pheochromocytomas and paragangliomas. Rather than representing areas of nuclear or nucleolar degeneration, the "inclusions" of these tumor cells represent deep invaginations of the cytoplasm into the nucleus. The great frequency of nuclear "inclusions" in pheochromocytomas is a reflection of the high degree of nuclear angulation and lobulation commonly seen in these tumors. PMID- 6249716 TI - Unusual histiocytic tumor of the small intestine. AB - A case of unusual sarcoma of the small intestine is described. Ultrastructural observation, enzyme histochemical studies, and functional analysis, such as phagocytic capacity and surface markers, were helpful in defining the neoplastic cells as histiocytes. Autopsy findings are presented. PMID- 6249717 TI - Immunohistochemical markers of histiocytic tumors. PMID- 6249720 TI - Spatial summation of monochromatic light in the visual system. PMID- 6249719 TI - Somatic cell hybridisation studies showing different gene mutations in Niemann Pick variants. AB - Cultured skin fibroblasts from patients with different clinical types of Niemann Pick disease were hybridized and sphingomyelinase activities were measured in the heterokaryon cell population. Both the natural substrate (3H-choline) sphingomyelin and the chromogenic analogue hexadecanoylamino-4 nitrophenylphosphorylcholine were used in the complementation analysis. In fusions between cells from type C Niemann-Pick disease with those from type A or B a clear restoration of sphingomyelinase activity occurred, whereas no complementation was found in other fusion combinations. The results indicate that at least two different genes are involved in the mutations leading to the different Niemann-Pick variants. PMID- 6249721 TI - Cell culture of infantile digital fibromatosis. AB - Two cell cultures were obtained from excised tumors of two cases of infantile digital fibromatosis (IDF). The cells had eosinophilic cytoplasmic inclusion bodies characteristic of IDF. Although the rate of cells bearing the inclusion bodies was high at the earlier passage levels, it was reduced to zero by the 15th passage of one of the cultures, but the cells of the other culture continued to produce the inclusion bodies even at the 30th passage. Chromosome analysis revealed both cultures to have tetraploid cells in approximately 8 to 12% in late passage levels. No viruslike particles were found in electron microscopy. No tumors developed when the cells were inoculated into athymic, nude mice subcutaneously. These cell cultures will be valuable for characterizing the eosinophilic inclusion bodies and determining the origin of the tumors. PMID- 6249722 TI - Delayed brain necrosis in irradiated adenoid cystic carcinoma nose--a case report. PMID- 6249723 TI - Mucinous adenocarcinoma of prostate. PMID- 6249718 TI - On procaryotic gene expression in eucaryotic systems. AB - Numerous types of interaction between pro- and eucaryotes exist in nature, from the endosymbiosis of some bacteria with unicellular organisms and insects to the complex systems of bacterial flora associated with the skin and intestines of animals and man, and nitrogen-fixation and crown-gall tumor induction in plants. Until recently, such interactions were not thought to include genetic transfer, but an increasing body of evidence points to the probability of similar naturally occurring exchanges with wide-ranging implications for evolution and genetic manipulation. Experiments to elucidate the possible effects of procaryotic genes in eucaryotic systems have included in vitro and in vivo studies with both plant and animal systems, for instance the translation of bacterial messenger RNAs in the wheat germ and rabbit reticulocyte systems and the introduction of bacterial genes into plant protoplasts, animal cells and whole organisms. In the present paper we have tried to summarize the results of experiments involving the uptake, replication, transcription, translation and integration of procaryotic genes in various eucaryotic systems and to discuss the implications of such findings for basic research as well as for possible biomedical applications. Awareness of the possibility of procaryotic-eucaryotic genetic interactions may help to elucidate unresolved questions in pathology, such as possible involvement of the intestinal flora in carcinogenesis, as well as to provide valuable probes of eucaryotic control mechanisms and new approaches in agricultural genetic engineering. PMID- 6249724 TI - Bovine-derived spinal cord protein (SCP) protects guinea pigs from experimental allergic encephalomyelitis (EAE) - a confirmatory report. AB - An axonally localized, non-encephalitogenic protein derived from bovine spinal cord can protect guinea pigs from EAE following challenge with bovine myelin basic protein. Protection from neurologic signs is significant although CNS pathology is present. The protective regimen apparently varies depending upon the species and strain of animal; this specific requirement may account for a previous negative report. PMID- 6249725 TI - On the mechanism of action of low molecular weight inhibin from ram testes. PMID- 6249726 TI - Studies on some enzymes & metabolites of guineapig testis following X irradiation. PMID- 6249727 TI - 3'5' Cyclic AMP phosphodiesterase activity in the testes & fat body & the effect of prostaglandins & cAMP in the green frog Rana hexadactyla Lesson. PMID- 6249728 TI - Effect of O-chlorobenzylidene malononitrile (CS) on tissue glycolysis & oxidation. PMID- 6249729 TI - Action of polymyxin B on liposomes prepared from cholera & El Tor Vibrios. PMID- 6249730 TI - Chlorpromazine induced cytological & enzymological changes in the male reproductive organs & the endocrine glands in rat-tailed bat Rhinopoma kinneari (Wroughton). PMID- 6249731 TI - Partial purification & properties of fructose-1,6-diphosphatase from the deep-sea fish Indocibium guttattam. PMID- 6249732 TI - Effect of different levels of Bengal gram protein on the ferroenzymes of rat liver. PMID- 6249733 TI - Action of ACTH & hydrocortisone on pituitary ACTH cells in male & female of the squirrel Funambulus pennanti (Wroughton). PMID- 6249734 TI - Propane-1,2-diol-induced in vivo & in vitro changes in rat erythrocytes. PMID- 6249735 TI - Central actions and brain receptor binding of angiotensin II: Influence of sodium intake. AB - The effects of dietary sodium on the central actions of angiotensin II (AII) and on 125I-AII binding to brain membranes were investigated in rats fed a low-sodium or control diet and implanted with a permanent cannula into the lateral cerebral ventricle. Blood pressure (BP) responses to AII injections intracerebroventricularly (i.v.t.) were blunted in sodium-deficient rats compared with controls. The BP increases in response to i.v.t.-injected Carbachol were the same in the two groups. In sodium-depleted rats, water intake was lower than in controls after AII given i.v.t.; higher after 1.5% NaCl i.v.t.; and unchanged after Carbachol i.v.t. The pressor response to AII given i.v.t. was higher in spontaneously hypertensive rats (SHR) than Wistar-Kyoto (WKY) control rats. This hyperresponsiveness to central AII was abolished by feeding a low-sodium diet. Specific 125I-AII binding in vitro to brain membranes was consistently lower in sodium-depleted rats. The results suggest that sodium depletion modifies the central actions of AII. This may be related in part to changes in the binding properties of AII receptors in the brain. PMID- 6249736 TI - Plasma cortisol and its relation to malnutrition. PMID- 6249737 TI - [The daily use of a dental plaque detector]. PMID- 6249738 TI - Bactericidal mechanisms of human breast milk leukocytes. AB - The functional capacity of human breast milk phagocytes was evaluated with both bactericidal and biochemical assays. Acridine orange was used as a vital stain for bacteria to directly visualize phagocytosis and killing. Bactericidal capabilities were further examined by colony count and chemiluminescent methods. Cytocentrifuged specimens stained for myeloperoxidase exhibited enzyme activity in breast milk leukocytes equal to that of peripheral neutrophils. A radioisotopic assay of hexose monophosphate shunt activity demonstrated metabolic activity in breast milk leukocytes greater than that in peripheral blood neutrophils. However, the chemiluminescent response of breast cells was negligible, apparently the result of quenching secondary to fat present in the milk; preincubation of human blood leukocytes with the fatty layer of breast milk produced similar inhibition in the chemiluminescence assay. By most parameters breast milk phagocytes are at least equal to blood neutrophils. PMID- 6249739 TI - Passive immunity in calf rotavirus infections: maternal vaccination increases and prolongs immunoglobulin G1 antibody secretion in milk. AB - Ten heifers were inoculated on two occasions with an inactivated preparation of tissue culture-grown calf rotavirus, and a further ten heifers received a placebo vaccine. Serum anti-rotavirus antibody titers were significantly increased throughout pregnancy in the vaccinated group. After calving, the mean neutralizing antibody titer of colostral whey in control cows was 100, associated with immunoglobulins A and G1. No antibody was detected in the milk of these cows after the 4th day postpartum. The colostral whey from the vaccinated cows had a mean antibody titer of 20,452; 28 days after calving, the mean milk antibody titer was 320, associated mainly with immunoglobulin G1. Calves were challenged with a large oral inoculum of calf rotavirus at the 7th day of age. There was significant lengthening of the incubation and prepatent periods in calves born to vaccinated dams, but rotavirus-associated diarrhea of equal severity occurred in both groups. Evidence is presented which suggests that rotavirus antibody in milk can protect against a smaller challenge dose. Maternal immunization against rotavirus may be a practical proposition. PMID- 6249740 TI - Demonstration of cell envelope-bound exotoxin A in Pseudomonas aeruginosa. AB - The quantity of membrane-bound and extracellular exotoxin A in four strains of Pseudomonas aeruginosa was investigated. In strain PA-103, which is the prototype strain used for toxin production, all of the toxin was released into the growth medium and little toxin remained with the cell envelope. In a virulent strain from a clinical source, strain 119, exotoxin A was found in equal amounts in the growth medium and in the cell envelopes. An avirulent mutant of this strain, strain 119 (AP-), which was resistant to 800 microgram of polymyxin B per ml, had all the exotoxin A in a membrane-bound state and was unable to release exotoxin A into the growth medium. Thus, exotoxin A can be found in the membrane-bound form, in the extracellular form, or in both. The quantities of membrane-bound toxin and extracellular toxin vary with the strain P. aeruginosa. The polymyxin B-resistant mutant which is blocked in toxin release will be useful in studies of exotoxin A secretion. PMID- 6249741 TI - Age-dependent resistance of human alveolar macrophages to herpes simplex virus. AB - Studies in mice demonstrate an age-dependent susceptibility to disseminated herpesvirus infection which is mediated. at least in part, by a defect in macrophage antiviral function. We examined the growth of herpes simplex virus within human alveolar macrophages obtained by bronchopulmonary lavage from neonates, adults with a variety of immunosuppressive disorders, and healthy adult volunteers. At 24 h postinfection, mean viral titers in neonatal macrophages increased 19-fold over adsorbed virus levels, a highly significant increase when compared to either immunosuppressed or normal adult macrophages (P less than 0.0005). These findings indicate that human macrophages, like those of mice, exhibit age-dependent permissiveness for the replication of herpes simplex virus. This permissiveness may at least partially account for the clinical observation that human newborns are highly susceptible to disseminated herpes simplex virus infections, whereas adults are not. PMID- 6249742 TI - Effect of surface modifiers on an ectoenzyme: granulocyte 5'-nucleotidase. AB - Several agents that react with plasma membranes, namely the native lectins concanavalin A, Ricinus communis agglutinin, and wheat germ agglutinin, the modified lectin succinyl concanavalin A, and sodium meta-periodate, inhibited the ecto-5'-nucleotidase of intact guinea pig granulocytes. Stimulation of the enzyme was not observed at any lectin concentration. Inhibition by native lectins could be blocked or reversed by appropriate competing hapten sugars. In the case of concanavalin A, reversal could be achieved at 37 degrees C, but not at 5 degrees C. When lectins were used in combination with each other, the effects were found to be largely independent. However, when concanavalin A and R. communis agglutinin were applied together, complications arose because the former lectin binds to the latter as well as to the cell surface. To avoid some of the complexities inherent in studying intact cell 5'-nucleotidase and to gain additional information about the system, two broken cell enzyme preparations were also examined. The enzyme of plasma membrane-enriched fractions was inhibited by all five agents mentioned above. 5'-Nucleotidase solubilized in sodium deoxycholate was inhibited by the four lectins but stimulated by periodate. The effects of the surface modifiers on kinetic data for all three enzyme preparations are consistent with the hypothesis that direct interactions with the enzyme molecule give rise to changes in Vmax; interactions at membrane sites other than 5'-nucleotidase itself could cause increases in apparent Km values. Effects of interactions of ectoenzymes with plant lectins may serve as models for phenomena that result from cell-cell interactions or from interactions of animal cells with lectin-like components of the cellular environment. PMID- 6249743 TI - Expression of enzymic activity by exotoxin A from Pseudomonas aeruginosa. AB - Exotoxin A from Pseudomonas aeruginosa is a single polypeptide chain (M(r), 66,000) containing little if any adenosine 5'-diphosphate ribosyltransferase or oxidized nicotinamide adenine dinucleotide glycohydrolase activity. These activities have been demonstrated in the reduced intact toxin and in a peptide (M(r), 26,000) isolated from culture fluids or toxin preparations after storage. In this report we describe methods for generating enzymically active fragments by cleaving the fully or partially reduced exotoxin by proteolytic or chemical methods. Incubation of reduced toxin with chymotrypsin in the presence of oxidized nicotinamide adenine dinucleotide yielded an enzymically active peptide (M(r), 26,000) similar to the fragment characterized previously. Chemical cleavage by treatment of the reduced molecule with CNBr or 2-nitro-5 thiocyanobenzoate yielded fragments (M(r), 50,000 and 30,000, respectively) with similar activities. Also both adenosine 5'-diphosphate ribosyltransferase and oxidized nicotinamide adenine dinucleotide glycohydrolase activities were maximally expressed by the intact exotoxin after reduction of only two of its four disulfide bridges. Kinetic constants for activated whole toxin were similar to those of fragment A of diphtheria toxin. It is evident that in the native toxin the catalytic center is buried or distorted and that alterations in the covalent structure permit the center to become exposed or assume an active configuration. It is unknown whether reduction, proteolytic processing, or both occur during the course of toxin action on whole cells. PMID- 6249744 TI - Virus replication and localization of varicella-zoster virus antigens in human embryonic fibroblast cells infected with cell-free virus. AB - When human embryonic fibroblast cells were infected with cell-free varicella zoster virus, virus replication began between 8 and 14 h postinfection, and 4 more h werp required for the virus to infect neighboring cells. Virus-specific antigens were traced by the anticomplement immunofluorescent antibody technique. Virus antigen was first detectable 2 h postinfection in the cytoplasma, and diffuse fluorescence was observed in the nucleus as early as 4 h after infection. The nuclear fluorescence got brighter and cytoplasmic fluorescence was observed at 14 h postinfection. The spread of virus to the neighboring cells was recognized in 18 h postinfection. In the period of 24 to 48 h, antigens were seen at the nuclear membrane region and in the cytoplasma. Very strong fluorescence was restricted mainly to the nucleus, when phosphonoacetic acid or cytosine arabinoside was added to the infected cultures and the cells were incubated for 48 h. PMID- 6249745 TI - Peripheral infection in culture of rat sensory neurons by herpes simplex virus. AB - The peripheral infection of neurons from dissociated rat sensory ganglia by herpes simplex virus was studied with a newly developed tissue culture system. The results indicated that the virus arrives at the neuronal soma by an axoplasmic route and that at least some of these neurons are productively infected since eventually all cells in the culture appeared to be destroyed by the virus. This system showed promise in elucidating the possible roles of various effector cells, antiviral antibody, or antiviral compounds in the mechanism of herpes simplex virus latency. PMID- 6249746 TI - Marrow-dependent cells depleted by 89Sr mediate genetic resistance to herpes simplex virus type 1 infection in mice. AB - Adult mice resistant to infection with 10(6) plaque-forming units of a virulent strain of herpes simplex virus type 1 were treated with 89Sr to abrogate marrow dependent cell functions. Treated mice were found to be much more susceptible to the herpes simplex virus type 1 infection than untreated mice. The virus persisted in the visceral tissues of 89Sr-treated mice for 3 or more days postinfection but not in those of untreated mice. The virus also spread to the spinal cords of treated but not untreated mice. A marrow-dependent cell appeared to mediate resistance to herpes simplex virus type 1 by controlling the infection early after inoculation and not allowing the infection spread to the central nervous system. PMID- 6249747 TI - Presence of a virulence-associated plasmid in Yersinia pseudotuberculosis. AB - We have shown that Yersinia pseudotuberculosis can possess plasmids which are similar in size and function to the previously described Vwa plasmids of Y. enterocolitica. These plasmids are associated with the production of V and W antigens (calcium dependency) and pathogenicity of the organism. Further investigation of these plasmids from Y. pseudotuberculosis and Y. enterocolitica with restriction endonucleases revealed significant differences in their fragmentation pattern. PMID- 6249748 TI - Antibody-mediated neutralization of virus is abrogated by mycoplasma. AB - The ability of a mouse mammary tumor cell line to abrogate antibody neutralization of vesicular stomatitis virus was shown to be due to the presence of mycoplasma. The mycoplasma was isolated from the cell line and typed as Mycoplasma orale. Colonies of this mycoplasma were used to deliberately infect cell cultures which then gained the capacity to reactivate antibody-neutralized virus. The extent of the reactivation depended on the source of neutralizing antiserum. Other species of mycoplasma were tested and were found to reactivate neutralized virus, indicating that this may be a general phenomenon of mycoplasma contamination. PMID- 6249749 TI - Differences in attachment between herpes simplex type 1 and type 2 viruses to neurons and glial cells. AB - Fractions of nerve cell perikarya, synaptosomes, and astrocytic glia were prepared from human, monkey , rabbit, rat, and mouse brain tissue. The herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) binding capacity of these fractions was studied. Pretreatment of fractions with one type of HSV and the subsequent testing of adsorption of homotypic and heterotypic virus ws employed to reveal type selectivity of virus binding receptors. A higher density of HSV-1 than of HSV-2 selective receptors was found on synaptosomes and glial cells, except with mouse-derived preparations. Synaptosomal and glial cell preparations of mouse brains adsorbed both types of HSV well. Little or no adsorption was observed with HSV-1 and HSV-2 to neuronal perikarya. The type selectivity of HSV binding receptors on brain cells ws demonstrated on preparations of human synaptosomes and mouse glial cells. Some possible implications of the observations on the HSV infection of the nervous system are discussed. PMID- 6249750 TI - Specific immunoglobulin M response to hepatitis A virus determined by solid-phase radioimmunoassay. AB - Immunoglobulin M antibody to hepatitis A virus (IgM anti-HAV) is found in most patients with acute type A hepatitis. To determine the duration of this IgM response as well as to confirm that IgM anti-HAV is a specific marker for acute infection, we developed a solid-phase radioimmunoassay for IgM anti-HAV. This new assay is 25-fold more sensitive than a conventional blocking radioimmunoassay for anti-HAV, and interference due to rheumatoid factor was eliminated by simultaneously testing sera against virus-free control antigen. Maximum IgM anti HAV titers (1:6,400 to greater than or equal to 1:51,200) were detected during the first 30 days after the onset of illness. Although the IgM anti-HAV titer subsequently declined 64-fold over the ensuing 90 days, low-titer IgM anti-HAV (1:100 to 1:400) persisted in many sera for 90 to 150 days. Acute sera having an IgM anti-HAV titer of greater than or equal to 1:25,600 possessed a significantly higher mean IgM concentration (492 mg/dl) than acute sera with an IgM anti-HAV titer of less than or equal to 1:12,800 (344 mg/dl; P < 0.05). IgM anti-HAV titers did not correlate with other clinical or laboratory measures of disease severity. Detection of IgM anti-HAV proved to be both a highly specific (>99%) and a sensitive (>99%) method for the diagnosis of type A hepatitis. PMID- 6249751 TI - Comparative in vitro imunotoxicology of acyclovir and other antiviral agents. AB - In vitro lymphocyte blastogenic responses to the commonly employed mitogens phytohemagglutinin, pokeweed, and concanavalin A were evaluated when acyclovir, adenine arabinoside, cytosine arabinoside, and idoxuridine were added to the culture materials. Similarly, specific antigen-induced blastogenic responses, including herpes group antigens, and cytotoxicity and leukocyte inhibitory factor assays with herpes group viruses were determined in the presence and absence of antiviral agents. No depression of these cellular immmune responses by acyclovir or adenine arabinoside ws demonstrated. This was in contrast to the effects of cytosine arabinoside and idoxuridine, which severely inhibited blastogenic and cytotoxic responses but not leukocyte inhibitory factor production. Even at concentrations up to 20 microgram/ml, the antiviral agent acyclovir did not depress selected cellular immune responses that are important for successful elimination of invading herpes group viruses. PMID- 6249752 TI - Transfer of a CFA/I-ST plasmid promoted by a conjugative plasmid in a strain of Escherichia coli of serotype O128ac:H12. AB - Escherichia coli strains belonging to serotype O128ac:H12 and producing heat stable enterotoxin (ST) and colonization factor CFA/I were found in Sao Paulo in children with diarrhea, but not in normal children. Segregants occurred in such strains with a frequency of about 10%, which have lost the ability to produce ST and CFA/I at the same time. From one strain, both properties were transformed jointly in matings to an E. coli K-12 strain. All such ST+ CFA/I+ progeny had received two plasmids of length 97 and 64 kilobases in the matings. Insertion of a transposon, Tn5, carrying a gene for kanamycin resistance, into the two plasmids enabled us to select for kanamycin-resistant progeny in further matings. Analysis of such progeny strains in terms of plasmid content and production of ST and CFA/I revealed that the larger plasmid carries the genes for St and CFA/I and is not self-transmissible, whereas the smaller plasmid does not carry any recognizable phenotypic traits, but is conjugative and promotes cotransfer of the larger plasmid with a frequency of about 30%. PMID- 6249753 TI - Characterization of pneumococcal purpura-producing principle. AB - Purpura was grossly observable in albino mice 6 to 8 h after the intraperitoneal injection of sterile, deoxyribonuclease-treated, cell-free extracts prepared by sodium deoxycholate-induced lysis, sonic disruption, Parr bomb treatment, autolysis without sodium deoxycholate, or alternate freezing and thawing of washed suspensions of Streptococcus pneumoniae type I. Cell-free extracts obtained from sonically disrupted, heat-killed cells (100 degrees C for 20 min) did not contain purpurogenic activity. The reaction was maximal at approximately 24 h postinjection, started to fade slowly after 24 to 48 h, and usually was not grossly observable by 4 to 6 days postinjection. The purpura-producing principle (PPP) in the cell-free extract was purified by sequential ammonium sulfate precipitation, protamine sulfate precipitation, Sepharose 6B gel filtration, wheat germ lectin-Sepharose 6MB affinity chromatography, ribonuclease and trypsin treatment, and a second Sepharose 6B gel filtration step. The final preparation (i) contained glucosamine (5.6%), muramic acid (8.0%), neutral carbohydrate (12.8%), phosphate (8.0%), orcinol-reactive material (6.0%), and Lowry-reactive material (1.6%), and (ii) was free of detectable amounts of deoxyribonucleic acid, capsular polysaccharide, neuraminidase, cytolysin, and hyaluronidase. The isoelectric point and molecular size of the PPP were approximately pI 3.0 and several million daltons, respectively, and the activity remained in the supernatant fluid after centrifugation for 1 day at 105,000 x g. PPP activity was destroyed by incubation with egg white lysozyme and sodium metaperiodate but was resistant to trypsin, pronase, alpha-amylase, deoxyribonuclease, ribonuclease, alkaline phosphatase, pancreatic lipase, 7% trichloroacetic acid, 6 M urea, autoclaving (121 degrees C) for 30 min, and mild acid and alkali exposure. Our observations indicate that the PPP requires intact beta-1,4-glucosidic linkages for activity and support the working hypothesis that activity is associated with pneumococcal peptidoglycan solubilized by the bacterium's autolysin. PMID- 6249754 TI - In vitro activation of feline complement by feline leukemia virus. AB - Incubation of normal feline serum with purified feline leukemia virus (FeLV) at 37 degrees C for 30 min resulted in the activation of the complement system via the classical pathway as demonstrated by consumption of the C1, C4, C2, C3, and, to a lesser extent, the later C components. A similar finding was observed when normal human serum was substituted for normal cat serum. In contrast, complement dependent lysis of FeLV with normal feline serum as assayed by the release of ribonucleic acid-dependent deoxyribonucleic acid polymerase was one-third that of complement-dependent FeLV lysis with normal human serum. The levels of total hemolytic complement and neutralizing antibody in individual feline sera were also not proportional to the degree of virolytic activity. These observations indicate that the inefficient virolysis of FeLV by normal cat serum may be one of the factors contributing to the high incidence of leukemia observed in cats. PMID- 6249755 TI - Physical map of the conjugal plasmid of Neisseria gonorrhoeae. AB - The 24.5-megadalton plasmid of Neisseria gonorrhoeae is required for transfer of R-factors and possibly chromosomal markers during conjugal matings between gonococcal strains. We constructed a physical map of one such plasmid, pLE2451, using EcoRI, BglII, and HincII site-specific restriction endonucleases. The patterns of deoxyribonucleic acid digestion obtained with this plasmid were identical to those obtained with three other plasmids of similar size. PMID- 6249756 TI - Genetic and physical evidence for plasmid control of Shigella sonnei form I cell surface antigen. AB - Virulent Shigella sonnei synthesize a surface antigen (form I) which appears to be one of several requirements needed for this host to invade epithelial cells. Upon restreaking on agar media, form I cells readily and irreversibly generate form II cells that lack the form I antigen. All form II cells are avirulent. Plasmid deoxyribonucleic acid of form I and II cells of four different S. sonnei isolates, obtained from different areas of the world, was analyzed by agarose gel electrophoresis. A large plasmid (approximately 120 megadaltons in three of the strains) that is present in form I cells was always absent from form II derivatives. Attempts to transfer conjugally only this large plasmid from form I to genetically marked form II cells were unsuccessful. However, a composite molecule, apparently formed by recombination between the large form I plasmid and a self-transmissible plasmid, was found to transfer the form I trait. Transconjugant S. sonnei strains acquiring the form I antigen could retransfer this trait to S. sonnei, Shigella flexneri, or Salmonella typhi. These preliminary findings demonstrate that S. sonnei form I antigen synthesis is mediated by a large plasmid which is lost spontaneously at a relatively high frequency from S. sonnei strains. PMID- 6249757 TI - Lectin activity in Entamoeba histolytica trophozoites. AB - A lectin (carbohydrate-binding protein) has been found in extracts of a number of axenically grown trophozoites of Entamoeba histolytica strains. The strains grown in TYI-S-33 medium (Diamond et al., Trans. R. Soc. Trop. Med. Hyg. 72: 431-432, 1978) were HK-9, 200:NIH, and HM-1:IMSS. Strain HU-1:MUSC (HSC) was grown monoxenically in the same medium. The amoebic lectin agglutinated glutaraldehyde fixed erythrocytes. This activity was pH dependent and heat and oxidation sensitive, and was destroyed by proteolysis upon autoincubation. The relative agglutinating potency of the different strains of amoebae was investigated. Strain HSC had the highest specific activity (210 U/mg of protein), and strain HM 1 had the lowest (14 U/mg). One unit of hemagglutinating activity is defined as the amount of lectin present in 1 ml of extract which will agglutinate 1 ml of 4% erythrocytes. Upon subcellular fractionation of the lectin present in extracts of strain HK-9, two-thirds of the activity was detected in the soluble, nonsedimentable (100,000 x g, 60 min) fraction. Partial hydrolysate of chitin was found to inhibit the hemagglutinating activity. Among the oligosaccharides of N acetylglucosamine, the trimer and tetramer were the most potent inhibitors. The lectin was purified approximately 300-fold by a one-step affinity chromatography on a chitin column. The loading and elution from the column were based on the pH dependence of the lectin activity. PMID- 6249758 TI - Aerosol infection of mice with Bordetella pertussis. AB - Aerosol inhalation of Bordetella pertussis Tohama phase I resulted in a reproducible and uniform infection of mice (strain DDY or ICR). Mice in groups of 10 exposed for 30 min to aerosols generated from bacterial suspensions of 10(9) and 10(10) organisms per ml resulted in mean bacterial counts of 2.3 (+/- 0.3) X 10(4) and 1.0 (+/- 0.3) X 10(5) colony-forming units, respectively, in the lung of each animal. Subsequent studies using a 30-min aerosol inoculation of ICR mice with 2 X 10(9) bacterial cells per ml showed: (i) B. pertussis cells reached a maximum of about 10(7) colony-forming units per lung 14 days after inhalation. (ii) Deaths (10 to 100%, depending on mouse age) occurred 10 to 14 days after exposure. (iii) The lung weight and the leukocyte count increased from basal values of 100 mg and 10(4) leukocytes per mm3 to a plateau of 950 mg and 1.95 X 10(5) leukocytes per mm3, respectively, 14 days after challenge. (iv) There was a significantly reduced rate of body weight gain by infected mice compared to noninfected mice. (v) With mortality as the criterion for disease, susceptibility varied with the age of mice as follows: 10 days old greater than 18 greater than 28 greater than 49. (vi) Bacteria were associated with ciliated respiratory epithelial cells by scanning electron microscopy. PMID- 6249759 TI - Chemotaxin-induced changes in cyclic adenosine monophosphate levels in human neutrophils. AB - Incubation of the chemotactic agent N-formyl-methionyl-leucyl-phenylalanine with human neutrophils produced a rapid elevation of the intracellular level of cyclic adenosine monophosphate (cAMP). This cAMP spike occurred within 30 s after exposure and returned to normal by 5 min. PMID- 6249760 TI - Cervical carcinoma: detection of herpes simplex virus RNA in cells undergoing neoplastic change. AB - 3H-HSV-2 DNA has been hybridized in situ to frozen sectioned tissue from human cervical biopsies. RNA complementary to the virus-specific probe was detected in cells undergoing pre-malignant changes, but not in the cells of the fully developed squamous-cell cancer. PMID- 6249761 TI - H-2 associated resistance to leukaemia transplantation: natural killing in vivo. AB - Natural resistance in vivo was studied by injecting non-immunized mice with leukaemia cells prelabelled with the thymidine analogue 131I-iododeoxyuridine. There was a decrease in the survival of the leukaemia cell inoculum as determined by whole-body gamma counting, and a failure of the leukaemia cells to survive in the spleens of mice which were not H-2 identical with the transplant. H-2 associated resistance could be measured within 24 h of leukemia inoculation and was strongest in the spleen and absent from the liver. Although all strains of mice tested were able to resist H-2 non-identical cells, resistance in irradiated (800--900 R) mice was restricted to certain strains and their F1 hybrids, notably those of the C57BL family. Resistance in both non-irradiated and irradiated mice was not due to classical immunological rejection. Mice with either genetic or induced T-cell deficiency showed full resistance, and circulating preformed antibody could not account for the rejection observed. Treatment with silica or with 89Sr abrogated natural resistance in non-irradiated as well as irradiated animals; these treatments had previously been shown to abolish both bone-marrow graft rejection in irradiated mice and in vitro natural killing. Resistance against leukaemia transplantation in irradiated C57BL mice appeared to depend on Hh-1 (H-2D) incompatibility between the host and the graft, again suggesting that bone-marrow graft rejection, and perhaps natural killer activity, is a subset of a more general paraimmune or non-adaptive rejection mechanism. PMID- 6249762 TI - Bovine leukemia virus-specific antibodies in French cattle. III. Prevalence of the BLV-gp 51 radioimmunoassay for the detection of BLV-infected animals. AB - The control of the spread of BLV infection among cattle requires very sensitive methods of detection. The BLV-gp51 radioimmunoassay presents great advantages over the other serological methods, including the BLV-p24 radioimmunoassay. This is clear from studies of normal animals from the high-leukemia-incidence region which show that anti-gp51 antibodies reach higher titers than anti-p24 or may even exist alone. Moreover, a sequential survey reveals that the anti-gp antibodies appear earlier. On the other hand, it was not possible to detect a viral antigen expression in the tissues of the infected animals. PMID- 6249763 TI - Long-term T-cell-mediated immunity to Epstein-Barr virus in man. IV. Development of T-cell memory in convalescent infectious mononucleosis patients. AB - Under appropriate culture conditions, EB virus infection of lymphocytes from seropositive donors leads to regression of transformation, and this was shown previously to be due to activation in a secondary immune response to T lymphocytes inhibitory for the autologous lymphoblastoid cell line. Regression can be quantified by determining the number of cells required for its expression. To investigate the development of memory T cells with EB-virus specificity in the primary infection, a comparison was made of the capacity for regression of lymphocytes from 16 cases of infectious mononucleosis (IM) and 13 normal donors. With 9 normal seropositive donors a mean lymphocyte concentration of 4.6 X 10(5)/ml was required to achieve 50% regression. In contrast, with 8 cases of IM tested within 1 week of onset, a much higher mean lymphocyte concentration (3.7 X 10(6)/ml) was necessary. Six of these IM cases, and another not tested in the first week, were tested on several occasions between 5 and 23 weeks after onset, and showed a slight reduction in the mean cell concentration required for regression (1.5 X 10(6)/ml). Six additional were tested 23--83 weeks after onset by which time the cell concentration required for 50% regression (mean = 4.5 X 10(5)/ml) had reached the level shown by normal seropositive donors. Regression did not occur with lymphocytes from seronegative donors, even at the highest cell concentration. Recombination cultures of T-cell-depleted and T-cell-enriched lymphocyte populations from 3 IM cases in ratios of 1:7 to 7:1 showed that the failure of regression in acute IM was not due simply to lack of sufficient numbers of T cells. The results indicate that EB-virus-specific memory T-cell activity as detected by the regression test is absent in the acute phase of IM, becomes evident at low levels 5--23 weeks after onset, and reaches a maximum after about 6 months. PMID- 6249764 TI - AG-4 complement-fixing antibodies in cervical cancer and herpes-infected patients using local herpes simplex virus type 2. AB - The incidence of anti-AG-4 complement-fixing antibodies in Australian cervical carcinoma (CaCx), herpes simplex virus (HSV) type 1 and 2, and control patients, was investigated using local HSV strains. The local HSV strains (both HSV-IMI and HSV-2MI) were found, by neutralization experiments, to vary from the American prototype strains. All HSV-2-strains tested were able to induce AG-4 in 4-h infected HEp-2 cells. Anti-AG-4-complement-fixing antibodies were detected in 40% of dysplasia patients, 60% of carcinoma-in-situ patients, 75% of CaCx patients, 65% of CaCx post-operative patients, 88% of HSV-2 patients with active lesions, 10% of HSV-1 patients with active lesions, 10--20% of normal patients and 20% of patients with cancer, other than CaCx. The AG-4 test is tumour-specific in that it distinguishes CaCx from other cancer patients tested, but it cannot distinguish HSV-2 patients from CaCx patients. PMID- 6249765 TI - Activated T lymphocytes in infiltrates and draining lymph nodes of nasopharyngeal carcinoma. AB - Lymphocytes isolated from the tumors and draining lymph nodes of nasopharyngeal carcinoma (NPC) patients exhibit the following characteristics of immune activation: (1) stable E rosette formation, (2) natural attachment to various human cells, (3) sensitivity in vitro to the lytic effect of glucocorticoids. Although the NPC T cells attach in vitro to various cells they kill only EBV genome-carrying targets. These findings suggest the occurrence of a local cellular immune response in NPC, possibly directed to EBV-determined antigens. PMID- 6249766 TI - DDS 100 mg daily preventing permanent nerve damage in reversal reaction. PMID- 6249767 TI - [Influence of copper in combination with other trace elements on the activity of trypsin (author's transl)]. AB - The activity of trypsin was determined by using N alpha-Benzoyl-L-arginin-p nitroanilid (L-BAPA) as a substrate, and adding either the elements Cu, Zn, Fe, Ni, and Co alone or in combination with copper in the concentration range of 0.9 x 10(-7) to 0.9 x 10(-4) moles Men+/l. Cu and Zn don't elevate the activity of trypsin but if they are added separately in very small concentrations. They lower the activity at higher concentrations. The other trace elements elevate the trypsin activity over the whole concentration range investigated. When copper is used in combination with the other trace elements there is no additional effect on trypsin activity. Here activities are somewhere in between the values when elements are added separately. A competing effect for the bounding sites of the trypsin is supposed. In this way it is possible to explain the non-linearity of the turnover rate curves of the experiments with the combined trace elements. PMID- 6249769 TI - Bilateral malignant choroidal melanomas. PMID- 6249768 TI - Vitamins and alcoholism. III. Vitamin B6. PMID- 6249770 TI - The Bragg peak of proton beams for treatment of uveal melanoma. PMID- 6249771 TI - Improved single-dose metyrapone test. AB - One dose of metyrapone (1.5 g) administered at 6 AM, with subsequent measurement of plasma ACTH, 11-deoxycortisol, or 17-hydroxycorticosteroids (17-OHCS) (cortisol + 11-deoxycortisol) at noon and 2 PM allowed an accurate assessment of the pituitary-adrenal reserve. Eighteen subjects with a normal pituitary-adrenal reserve were studied before and after the administration of this single metyrapone dose. By noon, plasma ACTH rose from a premedication value of 39 +/- 22 (SD) to 193 +/- 104 pg/ml and 11-deoxycortisol, from 0.0 +/- 0.3 (SD) to 9.0 +/- 2.7 microgram/dl. By 2 PM, plasma 17-OHCS had increased from a premedication value of 5.0 +/- 1.5 (SD) to 16.0 +/- 1.8 microgram/dl. The differences between pre- and postmedication values were statistically significant for all indices measured (P less than 0.001). No overlap was found between values before and after metyrapone. This protocol eliminates the need for metyrapone administration every 4 h over a 24-h period. It offers the advantage of low dose and low toxicity. The integrity of the pituitary-adrenal axis can be demonstrated by measuring either plasma ACTH and 11-deoxycortisol or even 17-OHCS 6 to 8 h after the administration of this single metyrapone dose. PMID- 6249772 TI - Prevalence of serum antibody to reoviruslike agent in hospital patients in Israel. AB - The prevalence of antibody to reoviruslike agent was studied in serum from 350 hospitalized patients in the Tel Aviv area by the complement-fixation technique, with calf diarrhea virus as the antigen. There were 217 (62%) serum samples that showed evidence of antibody to reoviruslike agent. The highest prevalence was noted in postpartum women (95%) and in infants under one month of age (93%), the latter probably as the result of placental transfer. The presence of antibody declined rapidly in the first six months of life and rose sharply after this age. These findings accord with the high incidence of reoviruslike agent infection in these age groups, as previously reported. Above the age of three years, the prevalence of detectable antibody remained stable, ranging from 54.5 to 81.0% in various age groups. PMID- 6249773 TI - Isolated ACTH deficiency and primary hypothyroidism: volume-dependent elevation of antidiuretic hormone secretion in the presence of hyponatremia. AB - The unusual combination of isolated deficiency of ACTH secretion and primary hypothyroidism was demonstrated in a 72-year-old man. Antidiuretic hormone (ADH) levels were elevated despite severe hyponatremia. This abnormality was corrected by salt replacement and hydrocortisone therapy. These results suggest that the elevated ADH levels were appropriate for the volume depletion caused by the hypoadrenalism and were not related to the hypothyroidism. PMID- 6249774 TI - [Sexually communicable diseases: current status in the USA]. PMID- 6249775 TI - [Heterozygous Fabry's disease. Case report with electron microscopic studies]. AB - Fabry's disease is an inborn error of sphingolipid metabolism. The lysosomal hydrolase, alpha-galactosidase, is deficient. The full spectrum of symptoms (diffuse angiokeratoma, alpha-galactosidase deficiency) is only seen in males, who are always hemizygous. The heterozygous females may be asymptomatic and the enzyme activity can be normal. Such a case is reported. The diagnosis of this case was made by electron microscopic findings of the characteristic cellular lipid-inclusions within endothelial, perithelial, smooth muscle, and nerve sheath cells. The electron microscopic findings are a valuable clue to the diagnosis in these problem cases. The early diagnosis of female conductors is important for genetic counseling. PMID- 6249776 TI - Dietary fibre. PMID- 6249777 TI - [Suture material in intestinal anastomosis]. PMID- 6249778 TI - Ultrastructural localization of intestinal glucose-6-phosphatase activity during the postnatal development of the mouse. AB - The development of the endoplasmic reticulum (ER) and the ultrastructural localization of glucose-6-phosphatase activity have been studied in the proximal jejunum and distal ileum during the postnatal period. One day after birth, the amount and the repartition of ER in the jejunal enterocytes are similar to that observed in postweaning period. In the following days an extensive proliferation of SER is noted in the supranuclear zone of the absorbing cells. From day 7 till postweaning period a gradual decrease of the amount of SER is observed and after weaning, the ultrastructure of the enterocytes is similar to that in the adult mouse enterocytes. At all time, a positive reaction for G-6-Pase activity is observed in the cisternae of the endoplasmic reticulum and in the nuclear envelope. In the distal ileum, the SER is poorly developed one day after birth. During the first two weeks, the ER increases but no extensive proliferation of SER can be noted as in the jejunum. The G-6-Pase activity can be visualized in the rough and smooth endoplasmic reticulum as well as in the nuclear envelope. It appears that the proliferation of SER could be interpreted as the morphologic expression of an increased G-6-Pase activity. PMID- 6249779 TI - A new one-step method for the cytochemical localization of ouabain-sensitive, potassium-dependent p-nitrophenylphosphatase activity. AB - A new one-step method for the light and electron microscopic localization of the ouabain-sensitive, K-dependent p-nitrophenylphosphatase (K-NPPase) activity of the Na-K-ATPase complex is introduced. The incubation medium contains p nitrophenylphosphate (NPP) as substrate, lead citrate as the capture reagent, and dimethylsulfoxide (DMSO) as an activator. It is usable at the optimal pH of the K NPPase, which is about pH 9.0 in the presence of 25% of DMSO. The effects of fixation, lead concentration, and DMSO on the enzyme activity were studied using rat kidney as a test tissue. The fixation of tissues in a mixture of 2% paraformaldehyde and 0.5% glutaraldehyde for 60 min at 0 degrees--4 degrees C preserved 45% of the enzyme activity. In the absence of DMSO, lead citrate (4.0 mM) caused 82% inhibition of the enzyme activity in fixed tissue. However, the addition of DMSO (25%) caused about 3-fold activation of the remaining activity. Cytochemical demonstration of the ouabain-sensitive K-NPPase activity was successfully made by this method at both light and electron microscopic levels. PMID- 6249782 TI - Transmission delay of phase-locked cells in the medial geniculate body. AB - Over 4000 single unit recordings were obtained from the medial geniculate body (MGB) of nitrous oxide anaesthetized cats. Out of 1600 cells sensitive to tone bursts below 4 kHz, 10% were responding in a sustained manner. From these, 121 were tested for phase-locked responses. The general characteristics of these units have been described in a previous report. The central tendency of the discharges distribution within the period or mean phase angle was studied for many frequencies in 24 phase-locked units. For each of them, the mean phase angle shifts linearly with the frequency. The slope of these phase versus frequency lines is an accurate measure of the transmission delay from the cochlea to the MGB. This delay is a function of the unit's characteristic frequency and shows that the time spread introduced by the cochlea between the high and low frequency components of an acoustic signal is preserved up to the MGB. Subtracting the cochlear delay from this overall delay, the neural delay from the eighth nerve to the MGB was found to be 6.4 ms for neurons having a CF above 300 Hz; it was greater by 3 ms for cells with a CF below that frequency. PMID- 6249780 TI - Alteration in myocardial oxygen balance during exercise after beta-adrenergic blockade in dogs. AB - The effects of beta-adrenergic blockade upon myocardial blood flow and oxygen balance during exercise were evaluated in eight conscious dogs, instrumented for chronic measurements of coronary blood flow, left ventricular pressure, aortic blood pressure, heart rate, and sampling of arterial and coronary sinus venous blood. The administration of propranolol (1.5 mg/kg iv) produced a decrease in heart rate, peak left ventricular (LV) dP/dt, LV (dP/dt/P, and an increase in LV end-diastolic pressure during exercise. Mean coronary blood flow and myocardial oxygen consumption were lower after propranolol than at the same exercise intensity in control conditions. The oxygen delivery-to-oxygen consumption ratio and the coronary sinus oxygen content were also significantly lower. It is concluded that the relationship between myocardial oxygen supply and demand is modified during exercise after propranolol, so that a given level of myocardial oxygen consumption is achieved with a proportionally lower myocardial blood flow and a higher oxygen extraction. PMID- 6249781 TI - Effect of hydrostatic pressure on ion transport and metabolism in human erythrocytes. PMID- 6249783 TI - In vitro activity of mecillinam and mecillinam/ampicillin combinations on Proteus species. PMID- 6249784 TI - Spectrophotometric determination of inhibitory effects of CP-45899 on beta lactamase with benzylpenicillin and nitrocefin. PMID- 6249785 TI - On-calcium periodate reaction method for analysis of ephedrine sulfate in solid dosage forms: collaborative study. PMID- 6249786 TI - Glutamine and related analogs regulate guanosine monophosphate reductase in Salmonella typhimurium. AB - The addition of a glutamine analog, 6-diazo-5-oxo-L-norleucine, or an inhibitor of glutamine synthetase, L-methionine-dl-sulfoximine, to the growth media of most Salmonella typhimurium strains resulted in a marked elevation of guanosine monophosphate reductase levels. The elevation caused by either compound required protein synthesis and could be antagonized by exogenous glutamine. In addition, when glutamine auxotrophs were grown in suboptimal concentrations of glutamine, the guanosine monophosphate reductase levels were increased. It is postulated that glutamine or a product of its metabolism may function under normal conditions as a negative regulatory element in the control of guanosine monophosphate reductase and that decreased effective intracellular levels of glutamine result in an increase in the level of the enzyme. PMID- 6249787 TI - Molecular comparison of plasmids encoding heat-labile enterotoxin isolated from Escherichia coli strains of human origin. AB - The molecular properties of enterotoxin (Ent) plasmids from 12 Escherichia coli strains of human origin were examined. Ten strains belonged to the O78 serogroup, and the remainder were of serogroup O7 or O159. Eleven plasmids coded for heat labile enterotoxin (LT), and one coded for heat-stable enterotoxin (ST) and LT. The results of restriction enzyme digests and deoxyribonucleic acid reassociation experiments showed that all of the Ent plasmids were related, and supported the subdivision of the LT plasmids into three groups based on their genetic properties (M. M. McConnell et al., J. Bacteriol. 143: 158-167, 1980). Within group 1, two plasmids from South African strains were indistinguishable but differed in EcoRI and HindIII digests from the LT plasmid that originated from an Ethiopian strain. The three plasmids had >70% homology. The two non autotransferring group 2 plasmids identified in O78.H11 strains from Bangladesh were indistinguishable. The group 3 plasmids were from strains belonging to serogroups O7 and O78 isolated in Bangladesh, India, and Thailand. They shared >95% homology but showed slight differences in fragment patterns when treated with EcoRI and HindIII. There was 60 to 70% homology between the plasmids of groups 1 and 3, and the group 2 plasmid had 40 to 50% homology with members of these two groups. The autotransferring Ent plasmids had up to 40% homology with R factors of incompatibility groups FI, FII, and FIV. PMID- 6249788 TI - Genetic control of hydroxamate-mediated iron uptake in Escherichia coli. AB - Cells of Escherichia coli can derive iron from a variety of chelators (siderophores) in addition to enterochelin, the catechol derivative excreted by many enteric bacteria. The genetic control of hydroxamate siderophore utilization was investigated in mutants of E. coli K-12 selected for resistance to lethal agents which adsorb to the tonA protein of the outer membrane (albomycin, colicin M, and phages T5 and phi80). Many of the mutants were unable to utilize hydroxamate siderophores as an iron source. This phenotype was termed Fhu, for ferric hydroxamate uptake. Mutants carrying lesions in the tonA region of the chromosome were studied and fell into several types. Members of one class had lost some or all of the tonA receptor protein's functions in that they were resistant to the lethal agents and unable to utilize ferrichrome and its analogs, although able to respond to the hydroxamate rhodotorulic acid (FhuA phenotype). Other mutants were unable to utilize any of the hydroxamate siderophores tested and were resistant to albomycin, althogh many were sensitive to the other lethal agents (FhuB phenotype). Members of these classes lacked ferrichrome-mediated iron uptake. Strains carrying transposon Tn10 insertions in fhuA (previously termed tonA) lacked the 78,000-molecular-weight outer membrane protein previously described; insertions in fhuB retained this protein and had no detectable change in outer membrane composition. Three-point transduction crosses revealed the gene order to be pan-fhuA-fhuB-metD in the min 3.5 region of the chromosome map. Complementation analyses with F' merodiploid strains showed that fhuA and fhuB comprise separate transcription units which are both required for utilization of ferrichrome. Response of diploid strains to rhodotorulic acid suggested the existence of a third gene, fhuC, required for utilization of this siderophore, but not ferrichrome. It is suggested that fhuB encodes a transport component in the cytoplasmic membrane that is necessary for the uptake of all hydroxamate siderophores following their receptor-mediated passage across the outer membrane. PMID- 6249789 TI - Genetic control of tyramine oxidase, which is involved in derepressed synthesis of arylsulfatase in Klebsiella aerogenes. AB - Mutants of Klebsiella aerogenes with three types of mutations affecting regulation of tyramine oxidase were isolated by a simple selection method. In the first type, the mutation (tynP) was closely linked to the structural gene for tyramine oxidase tynA). The order of mutation sites was atsA-tynP-tynA. In the second type, the mutation that relieves catabolite repression of the syntheses of several catabolite repression-sensitive enzymes are not linked to the tyn gene by P1 transduction. These strains contained high levels of cyclic adenosine 5' monophosphate when grown on glucose. The third type of mutation, in which tyramine oxidase was synthesized constitutively, was shown by genetic analysis to involve mutations of tynP and tynR. The tynR gene was not linked to tynA. Results using the constitutive mutants showed that the constitutive expression of the tynA gene resulted in depression of arylsulfatase synthesis in the absence of tyramine. PMID- 6249790 TI - Conservation and variation of nucleotide sequences within related bacterial genomes: Escherichia coli strains. AB - Changes in the patterns produced by annealing restriction endonuclease digests of bacterial genomes with probe deoxyribonucleic acids (DNAs) containing small portions of a bacterial genome provide sensitive indicator of the degree of nucleotide sequence relatedness that exists in localized regions of the genomes of closely related bacteria. We have used five probe DNAs to explore the relatedness of parts of the genomes of six laboratory Escherichi coli strains. A range in in the amount of variability in the positions of restriction enzyme cleavage sites in the selected portions of the genomes was found. Portions of the genome that are believed to be inacative were more variable than portions that contained functional genes: the sites in and near regions of homology to phage lambda DNA in the genome showed the greatest variability. These regions probably represent remnants of cryptic prophages. Variability was assessed pairwise among four of the E. coli strains and ranged from 5 to > 25% base pair substitutions in the lambda-related regions. In contrast, the endonuclease cleavage sites in the trp, tna, lac, thy regions, and one other as-yet-unidentified segment of the genome were more highly conserved. It seems likely that these sites lie in genetic locations that are subject to functional constraints. PMID- 6249791 TI - Regulation of aspartokinase III synthesis in Escherichia coli: isolation of mutants containing lysC-lac fusions. AB - Mutants containing fusions of the lac gene to the lysC gene were isolated. In these, the expression of beta-galactosidase was regulated by lysine (and arginine), as previously described for aspartokinase III. PMID- 6249792 TI - Construction of an Hfr strain useful for transferring recA mutations between Escherichia coli strains. AB - Strain JC10240 (Hfr PO45 srlC300::Tn10 recA56 thr-300 ilv-318 rpsE300) was constructed. On account of the close linkage of Tn10 to recA56, the latter can be moved to other Escherichia coli (and closely related) strains in transductional or conjugational crosses selecting resistance to tetracycline. PMID- 6249794 TI - Adenosine 3' : 5'-monophosphate binding activity and guanosine 3' : 5' monophosphate binding activity during adrenocorticotropic hormone stimulation in rat adrenal gland. PMID- 6249793 TI - Isolation of two protein-free and chemically different lipopolysaccharides from Bordetella pertussis phenol-extracted endotoxin. AB - Endotoxin prepared from several Bordetella pertussis strains in both immunological phases I and IV gave two lipopolysaccharide peaks (LPS-I and LPS II) when analyzed on hydroxylapatite columns in a phosphate buffer containing 0.1% sodium dodecyl sulfate; these lipopolysaccharides, present in the ratio of 2:3, are true endotoxins by both chemical and biological criteria. Endotoxins isolated from Escherichia coli, Salmonella typhimurium, and Shigella flexneri gave single lipopolysaccharide peaks when analyzed by the same procedure. Upon hydrolysis with acetic acid (pH 3.4) at 100 degrees C for 1 h, LPS-I released a polysaccharide (PS-I); the linkage broken was that of the glycosidic bond of a non-phosphorylated 3-deoxy-oct-2-ulosonic acid. Treatment with 0.25 M mineral acid at 100 degrees C for 30 min was required to free the polysaccharide moiety (PS-II) of LPS-II, the linkage broken being the glycosidic bond of a phosphorylated 3-deoxy-oct-2-ulosonic acid. Chemical and physical differences of the polysaccharide moieties PS-I and PS-II present in LPS-I and LPS-II have been described previously (25). By using the technique of 125I labeling, it was shown that the totality of labeled proteins present in the endotoxin extracted from Bordetella pertussis by the phenol-water procedure could be separated from the lipopolysaccharide by column chromatography on hydroxylapatite; it follows that these proteins are not linked by covalent bonds to the lipopolysaccharide. PMID- 6249796 TI - Acid adenosine triphosphatase from chicken liver lysosomes. I. Partial purification and some properties. PMID- 6249795 TI - Superoxide anion production from guinea pig macrophages stimulated with immune complexes of different IgG subclasses. AB - Guinea pig peritoneal macrophages produced superoxide anions (O2-) when reacted with ovalbumin complexes of homologous IgG1 and IgG2 antibodies. In this reaction, IgG2 complexes were about three times as active as IgG1 complexes. But the susceptibility of IgG1 complexes to phagocytosis by the cells appeared to be indistinguishable from that of IgG2 complexes. The avidity of IgG1 complexes in the antigen excess zone for Fc receptors on the cells was lower than that of the IgG2 counterparts. The amount of IgG1 complex bound to the cells, however, did not significantly differ from that of IgG2 complexes when compared using each complex at the equivalence zone which showed maximal effector functions on the cells. The binding of Clq to IgG2 complexes increased markedly the amounts of complexes bound to the cells, but it reduced O2- generation. These results suggest that the difference in abilities of IgG1 and IgG2 complexes to promote O2 generation may be caused by different structures of the Fc parts or their antigen complexes involved in priming macrophages for O2- generation. PMID- 6249797 TI - Effect of cholesterol on human erythrocyte membrane. A spin label study. AB - The effect of cholesterol on the membrane fluidity of human erythrocytes has been studied by electron spin resonance (ESR) spectroscopy, sensing the motion of androstane and fatty acid spin labeles in the cell membrane and in vesicles made from extracted phospholipids. 1. Androstane spin label (ASL) was incorporated from ASL-containing phospholipid vesicles into the erythrocyte membrane, essentially by a partition mechanism in proportion to their phospholipid contents. 2. On increasing the cholesterol or ASl content in the cell membrane, the spin label was gradually immobilized. 3. ASL motion in the cell membrane seemed to be primarily determined by the cholesterol/phospholipid molar ratio, regardless of the membrane protein-lipid interaction, as judged from the temperature effects on the ESR spectra of both membranes. 4. However, glutaraldehyde pretreatment induced considerable changes of the cholesterol-lipid interaction in the cell membrane, i.e., strong immobilization and cluster formation of ASL were observed. PMID- 6249798 TI - Order of release of ADP and Pi from phosphoenzyme with bound ADP of Ca2+ dependent ATPase from sarcoplasmic reticulum and of Na+, K+-dependent ATPase studied by ADP-inhibition patterns. AB - The inhibition of Ca2+-dependent ATPase from SR [EC 3.6.1.3] by ADP was of mixed type under both low Ca2+ and high Mg2+ concentration and high Ca2+ and low Mg2+ concentrations. On the other hand, the inhibition of Na+, K+-dependent ATPase [EC 3.6.1.3] by ADP was of competitive type in the presence of low and high K+ concentrations. These results suggest that ADP is released before Pi from the phosphoenzyme with bound ADP (EPADP) in the case of Ca2+-ATPase, but that Pi is released before ADP in the case of Na+, K+-ATPase. PMID- 6249799 TI - Amino acid sequence of cytochrome c3 from Desulfovibrio vulgaris, Miyazaki. AB - The complete amino acid sequence of a tetrahemoprotein, cytochrome c3 isolated from Desulfovibrio vulgaris, Miyazaki, was determined to be Ala-Pro-Lys-Ala-Pro Ala-Asp-Gly-Leu-Lys-Met-Asp-Lys-Thr-Lys-Gln-Pro-Val-Val-Phe -Asn-His-Ser-Thr-His Lys-Ala-Val-Lys-Cys-Gly-Asp-Cys-His-His-Pro-Val-Asn-Gly-Lys-Glu-Asn-Tyr-Gln-Lys Cys-Ala-Thr-Ala-Gly-Cys-His-Asp-Asn-Met-Asp-Lys-Lys-Asp-Lys-Ser-Ala-Lys-Gly-Tyr Tyr-His-Ala-Met-His-Asp-Lys-Gly-Thr-Lys-Phe-Lys-Ser-Cys-Val-Gly-Cys-His-Leu-Glu Thr-Ala-Gly-Ala-Asp-Ala-Ala-Lys-Lys-Lys-Glu-Leu-Thr-Gly-Cys-Lys-Gly-Ser-Lys-Cys His-Ser. The highest homology was found between the sequence of cytochrome c3 of D. vulgaris, Miyazaki, and that of D. vulgaris, Hildenborough, on comparison among various cytochrome c3'S. These two consist of 107 amino acid residues and they differ by 14 residues. PMID- 6249800 TI - A rapid micro-assay method for gelatinolytic activity using tritium-labeled heat denatured polymeric collagen as a substrate and its application to the detection of enzymes involved in collagen metabolism. AB - A rapid micro-assay method for gelatinolytic activitiy has been developed using 3H-labeled heat-denatured polymeric collagen (gelatin) as a substrate to investigate enzymes involved in the post-collagenase catabolism of collagen. The method is based on the incubation of gelatin with enzyme followed by determination of the enzyme digestion products soluble in 67% dioxane. It is sensitive enough to detect microgram levels of gelatin fragments, and can be employed over wide ranges of pH and ionic strength. By applying the method to an embryonic chick skin culture system, three gelatinolytic enzyme fractions which showed high, limited and no caseinolytic activities were demonstrated to be separable by gel chromatography. PMID- 6249801 TI - Nuclear translocation of the 1,25-dihydroxycholecalciferol receptor in mouse kidney. AB - We have recently demonstrated that cytosol from mouse kidney contains a receptor like binding protein for 1,25-dihydroxycholecalciferol (1,25-(OH)2D3). The present studies were undertaken to investigate whether this component undergoes nuclear translocation, thus adding support to the contention that this binding moiety represents a receptor for 1,25-(OH)2D3. Kidney slices from vitamin D deficient mice were incubated with 1,25-(OH)2[3H]D3 and specific binding was assessed in cytosol and 0.3 M KCl extracts of isolated nuclei. The appearance of specific nuclear-bound 1,25-(OH)2[3H]D3 exhibited a saturation time course and the increase in nuclear binding was accompanied by a concomitant decrease in cytoplasmic binding such that, by 120 min, approximately 80% of specifically bound 1,25-(OH)2[3H]D3 was associated with the nuclear fraction and approximately 20% remained in the cytoplasmic compartment. The nuclear transfer was found to be temperature-dependent and specific for the dihydroxy metabolite. Both the cytoplasmic and nuclear receptors sedimented at 3.2 S in 0.3 M KCl sucrose density gradients. However, under low salt conditions, the cytoplasmic receptor was transformed to yield an approximately 5.4 S peak while the nuclear receptor sedimented unchanged t 3.2 S. In summary, the cytoplasmic 1,25-(OH)2D3 receptor in mammalian kidney undergoes temperature-dependent nuclear translocation and the cytoplasmic and nuclear forms of the receptor can be distinguished by their sedimentation properties. PMID- 6249802 TI - Characterization of the heat-stable polypeptide of the ATP-dependent proteolytic system from reticulocytes. AB - A heat-stable polypeptide from rabbit reticulocytes has been previously shown to be required for ATP-dependent protein breakdown (Ciechanover, A., Hod, Y., and Hershko, A. (1978) Biochem. Biophys. Res Commun. 81, 1100-1105) and to form covalent conjugates with proteins in an ATP-requiring reaction (Ciechanover, A., Heller, H., Elias, S., Haas, A.L., and Hershko, A. (1980) Proc. Natl. Acad. Sci. U.S.A. 77, 1365-1368). We now describe its purification, characterization, and tissue distribution. Its presence in erythrocytes at high level makes this a possible preferred source in the future. PMID- 6249803 TI - Ubiquitin is the ATP-dependent proteolysis factor I of rabbit reticulocytes. AB - A small heat-stable polypeptide, ATP-dependent proteolysis factor 1 (APF-1), is an essential component of the ATP-dependent proteolytic system of rabbit reticulocytes (Ciechanover, A., Hod, Y., and Hershko. A. (1978) Biochem. Biophys. Res Commun. 81, 1100-1105). The following evidence supports the view that APF-1 is ubiquitin, a highly conserved heat-stable polypeptide found universally in nature: 1) APF-1 and ubiquitin (generously given by G. Goldstein) yield co migrating bands on five polyacrylamide gel electrophoresis systems and in isoelectric focusing; 2) amino acid analysis shows excellent agreement between the two proteins; 3) APF-1 and ubiquitin give similar specific activity, in activating the ATP-dependent proteolysis system; 4) 125I-APF-1 and 125I-ubiquitin form electrophoretically identical covalent conjugates with endogenous reticulocyte proteins. Recently, such conjugates have been proposed as the active intermediates in ATP-dependent proteolysis (Ciechanover, A., Heller, H., Hershko, A., Haas, A.L., and Rose, I.A. (1980) Proc. Natl. Acad. Sci. U.S.A. 77, 1783 1786). Thus, ubiquitin is an essential component of the ATP-dependent system in reticulocytes and a similar role in degradation and proteolytic processing in other cells is likely. PMID- 6249804 TI - Insulin and glucagon as a new regulator system for tryptophan oxygenase activity demonstrated in primary cultured rat hepatocytes. AB - The basal activity of tryptophan 2,3-dioxygenase (EC-1.13.11.11) in primary cultured rat hepatocytes decreased during culture, but addition of either tryptophan (2.5 x 10(-3) M) or dexamethasone (1 x 10(-6) M) could prevent the decrease. Addition of both compounds caused severalfold induction of activity. Glucagon (1 x 10(-8) M) alone did not induce the activity, but its inductive effect in combination with tryptophan was similar to that of tryptophan plus dexamethasone. The effect of glucagon was additive with those of tryptophan and dexamethasone and hence the highest induction (7-fold) was achieved by addition of all three inducers. Glucagon could be replaced by dibutyryl cyclic AMP (1 x 10(-5) M). Insulin (1 x 10(-8) M) inhibited the inductions by glucagon and dexamethasone, but not that by tryptophan. Cycloheximide inhibited the inductions by all three inducers, but actinomycin D inhibited only the induction by dexamethasone. These results suggest that the three compounds have different mechanisms of induction of tryptophan oxygenase activity: tryptophan prevents enzyme inactivation, dexamethasone may stimulate enzyme synthesis at the level of transcription, and glucagon may enhance the synthesis at the translational level. PMID- 6249805 TI - Insulin stimulation of pyruvate dehydrogenase in an isolated plasma membrane mitochondrial mixture occurs by activation of pyruvate dehydrogenase phosphatase. PMID- 6249806 TI - Enzymatic analysis of 5-methylcytosine content in eukaryotic DNA. Study of intracellular Simian Virus 40 DNA. AB - An enzymatic method is described for the analysis of the content of 5 methylcytosine in the DNA of eukaryotic cells. The conventional acid hydrolysis procedure was found to result in variable deamination of 5-methylcytosine into thymine, making the exact quantitation difficult. We applied the enzymatic method for the analysis of a simple eukaryotic viral genome. Viral and cell DNA in Simian Virus 40-infected monkey kidney cells was labeled with [methyl 3H]methionine in vivo and their 5-methylcytosine content was analyzed. The content of 5-methylcytosine per thymine in the total intracellular viral DNA was found to be less than 10(-4) of the host DNA. The implication of this result with regard to eukaryotic gene expression is discussed. PMID- 6249807 TI - Electron spin resonance studies of bovine plasma amine oxidase. Probing of the environment about the substrate-liberated sulfhydryl groups in the active site. AB - A series of nitroxide spin-labeled reagents have been employed to explore the environment of the cysteine residues in bovine plasma amine oxidase. When the enzyme was reduced by substrate or phenylhydrazine, 1 essential sulfhydryl residue/subunit was liberated. This cysteine residue was reacted then with the spin label 3-(maleimido-methyl)-2,2,5,5-tetramethyl-1-pyrrolinyloxyl. The ESR spectra of the labeled enzyme derivatives suggested that this essential sulfhydryl residue is located in a pocket, whereas the nonessential sulfhydryl residues are probably located near the surface. By varying the length of the nitroxide spin-labeled N-ethylmaleimide derivatives, it was determined that the liberated essential cysteine residues are in a restricted environment. The ESR spectral data also suggested that the nitroxide radical and the essential copper in the enzyme do not interact with one another. The effect of ionic strength, pH, and urea denaturation on the environment of the essential sulfhydryl residue were also investigated. PMID- 6249808 TI - Mitochondrial biogenesis during fungal spore germination. Biosynthesis and assembly of cytochrome c oxidase in Botryodiplodia theobromae. PMID- 6249809 TI - Alteration of the membrane lipid composition and infectivity of vesicular stomatitis virus by growth in a Chinese hamster ovary cell sterol mutant and in lipid-supplemented baby hamster kidney clone 21 cells. AB - The cholesterol and phospholipid composition of the membrane of vesicular stomatitis (VS) virus was altered by growth in a sterol auxotroph Chinese hamster ovary (CHO MI) host cell and by infection of CHO MI and baby hamster kidney (BHK) 21 cells supplemented with fatty acids and dimethylethanolamine. VS virus released from infected CHO MI sterol auxotroph cells grown in delipidated serum had a 50% lower ratio of cholesterol to phospholipid and an 80% drop in infectivity measured by plaque formation on L-929 cells compared with VS virus released from infected CHO MI cells grown in fetal calf serum. When VS virus was harvested from infected BHK-21 cells fed the choline analogue dimethylethanolamine, 29% of the membrane phospholipids were phosphatidyldimethylethanolamine (PDME); 87% of the PDME was located in the external monolayer of the virus membrane as determined by phospholipase C hydrolysis. Exogenous fatty acids added to the medium of cells infected with VS virus comprised up to 30% of the fatty acyl chains of the viral glycerophospholipids. The presence of PDME or unusual fatty acyl chains in the viral membrane had no effect on viral infectivity. These data indicate that the lipid composition of the VS virus membrane is determined primarily by the lipids available in the host cell and that only cholesterol content affects the biological activity of the virus membrane. PMID- 6249810 TI - Stimulation of in vitro mitochondrial protein synthesis by yeast cytoplasmic extracts is caused by guanyl nucleotides. AB - Micromolar concentrations of GDP or GTP stimulate protein synthesis by isolated yeast mitochondria 3- to 10-fold even if alpha-ketoglutarate and an ATP regenerating system are present. No stimulation is observed with GMP, UTP, CTP, TTP, and the nonhydrolyzable GTP analogues guanyl(beta, gamma-methylene) diphosphate and guanyl imidodiphosphate. This stimulatory effect of exogenously added guanyl nucleotides may answer the long standing question why protein synthesis by isolated mitochondria is so slow. It can also explain previous reports by two other laboratories that a high speed supernatant from yeast cells stimulates protein synthesis by isolated mitochondria. The supernatant contains nondialyzable GMP which is converted to GDP under the conditions used for assaying mitochondrial protein synthesis. The stimulatory effect of high speed supernatants is abolished by 5'-nucleotidase (which degrades GMP) or by trypsin (which destroys supernatant protein(s) necessary for converting GMP to GDP). No evidence was obtained that the stimulatory effect of high speed supernatants was caused by precursors to cytoplasmically made cytochrome c oxidase subunits. PMID- 6249811 TI - Identification of a protease inhibitor from rat peritoneal macrophages as poly(ADP-ribose). AB - Rat peritoneal macrophages contain a chymotrypsin-like protease and its specific inhibitor, both being associated with chromatin of the cells. The inhibitor was separated from the protease by gel filtration through a Sephadex G-75 column, further treated with trypsin, DNase and RNase, and then purified successively on Sephadex G-75, Sephadex G-25, and dihydroxyboryl Bio-Gel P-60 columns. The purified inhibitor had a molecular weight in the range from 2,000 to 3,500 and an absorption maximum at 260 nm at pH 7.0. When the inhibitor was digested by snake venom phosphodiesterase, the inhibitory potency was lost, yielding 5'-AMP and 2' (5'-phosphoribosyl)-5'-AMP as the digestion products which were identified by high pressure liquid chromatography. The inhibitory potency was neutralized specifically by anti-poly(ADP-ribose) antiserum. The profile of inhibition by the isolated inhibitor was nearly identical with that produced by authentic poly(ADP ribose). It was therefore concluded that the inhibitor isolated was identical with poly(ADP-ribose), whose chain length ranged from 4 to 7 ADP-ribosyl units. This is the first demonstration that a intracellular protease inhibitor can be endogenous poly(ADP-ribose). PMID- 6249812 TI - Activation of a complex of C1r and C1s subcomponents of human complement C1 by the third subcomponent C1q. PMID- 6249813 TI - Appearance of beta-adrenergic receptors and catecholamine-responsive adenylate cyclase activity during fusion of avian embryonic muscle cells. PMID- 6249814 TI - Changes in affinity of Na+- and K+-transport ATPase for divalent cations during its reaction sequence. AB - Previous experiments (Fukushima, Y., and Post, R.L. (1978) J. Biol. Chem. 253, 6853-6862) demonstrated that the Ca x phosphoenzyme of sodium- and potassium transport adenosine triphosphatase gradually becomes stable after dissociation of Ca2+ in the presence of a chelating agent such as 1,2-cyclohexylenedinitrilo tetraacetic acid. In the present study, we investigated whether the ADP- and K+ sensitive forms of the Ca x phosphoenzyme show different affinities for divalent cations. Our findings were as follows. (a) As the concentraion of Na+ was increased during phosphorylation of the enzyme with ATP at pH 7.4 and 0 degrees C, both the sensitivity to ADP and the amount of calcium-free phosphoenzyme increased in parallel. (b) For this Na+-dependent change, kidney enzyme required higher concentrations of Na+ than did brain enzyme. (c) In addition, the rate of dissociation of Ca2+ from the ADP-sensitive Ca x phosphoenzyme was faster than that from the K+-sensitive phosphoenzyme. It was thus concluded that Ca2+ binds to the ADP-sensitive phosphoenzyme less tightly than to the K+-sensitive phosphoenzyme. PMID- 6249815 TI - Interactions of K+ with (Na,K)-ATPase orientation of K+-phosphatase sites studied with inside-out red cell membrane vesicles. AB - Inside-out membrane vesicles from human red cells were used to investigate the side specificity of K+ interactions with the K+-activated phosphatase, a partial reaction of the (Na, K)-ATPase. In the absence of Na+ and ATP, K+ at moderate affinity sites at the extravesicular surface (cytoplasmic K+) stimulates activity, whereas intravesicular K+ (K+ normally at the extracellular surface) is without effect. In contrast, under conditions of phosphorylation of (Na, K) ATPase (Na+ and ATP present), K+ ions acting at high affinity sites at both surfaces are required. It is concluded that an enzyme x K complex is involved in K+-activated phosphatase activity and that it is formed either by interaction of cytoplasmic K+ with the dephosphoenzyme, or as a consequence of extracellular K+ binding and dephosphorylation of the phosphoenzyme formed in the presence of Na+ plus ATP. PMID- 6249816 TI - Proteolytic solubilization and modification of hormone-sensitive cyclic nucleotide phosphodiesterase. PMID- 6249817 TI - Characterization of insulin-sensitive phosphodiesterase in fat cells. I. Effects of salts and oxidation-reduction agents. PMID- 6249818 TI - Characterization of insulin-sensitive phosphodiesterase in fat cells. II. Comparison of enzyme activities stimulated by insulin and by isoproterenol. PMID- 6249820 TI - Human carbamylphosphate synthetase I. Stabilization, purification, and partial characterization of the enzyme from human liver. AB - Carbamylphosphate synthetase I from human liver was stabilized, purified, and partially characterized. The labile enzyme was stabilized in cell-free extracts by the presence of MgATP and dithiothreitol at pH 7.8. The stabilized enzyme was purified by a rapid procedure consisting of ion exchange chromatograhy and electrofocusing The native molecular weight of the enzyme was determined by gel filtration to be 190,000. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated a monomeric molecular weight of 165,000. The isoelectric point of the purified enzyme was 6.05, and only one species of active enzyme was observed during electrofocusing of both purified enzyme preparations and crude liver homogenates. The enzyme exhibited a pH optimum of 7.8. The apparent Michaelis constants for NH4+, HCO3-, MgATP, and the activator, N-acetyl L-glutamic acid, were 0.8, 6.7, 1.1, and 0.1 mM, respectively. PMID- 6249819 TI - Electron paramagnetic resonance studies of nitrosyl ferrous heme complexes. Determination of an equilibrium between two conformations. PMID- 6249821 TI - Purification and properties of eIF-2 phosphatase. AB - Eukaryotic initiation factor 2 (eIF-2) phosphatase has been purified 840-fold to apparent homogeneity from rabbit reticulocyte lysate. Native eIF-2 phosphatase has a Mr = 98,000, pI = 6.1, s20,w = 5.1, and a Stokes radius = 38 A. A subunit composition of one 60,000-dalton polypeptide and one 38,000-dalton polypeptide is indicated. The Km for [32P]eIF-2 is 30 microM and the Vmax = 1.1 nmol of phosphate released/min/microgram. The 38,000-dalton subunit of eIF-2 phosphatase does not co-electrophorese with the catalytic subunit of liver phosphorylase phosphatase, a type 1 protein phosphatase. The specificity of eIF-2 phosphatase for phosphorylation sites on th alpha- and beta-subunits of eIF-2 appears to be determined by the environment of the phosphatase and substrate. Both the alpha- and beta-subunits of [32P]eIF-2 are rapidly dephosphorylated by the purified phosphatase. In unfractionated lysate and in unfractionated lysate supplemented with an equivalent activity of the purified phosphatase, only the alpha-subunit of eIF-2 is dephosphorylated. This indicates other factors are present in the lysate which govern the dephosphorylation of eIF-2. PMID- 6249822 TI - Bacteriophage T7 DNA replication in vitro. Stimulation of DNA synthesis by T7 RNA polymerase. AB - Four T7 products, DNA polymerase, gene 4 protein, RNA polymerase, and DNA binding protein, have been purified from phage-infected cells. It has been previously shown (Hinkle, D. C., and Richardson, C. C. (1975) J. Biol. Chem. 250, 5523-5529; Kolodner, R., and Richardson, C. C. (1978) J. Biol. Chem. 253, 574-584) that two T7 products, DNA polymerase and gene 4 protein, catalyze extensive synthesis on duplex T7 DNA containing single strand breaks. However, the T7 DNA polymerase purified by our procedure does not efficiently contribute in this reaction, although the preliminary evidence suggests that this enzyme may be the native form of the DNA polymerase. Such inefficient T7 DNA synthesis is greatly augmented by adding the third T7 product, namely T7 RNA polymerase. This DNA synthesis apparently requires transcription, since each of the four rNTPs must be present. The rate of synthesis is increased about 2-fold by the addition of T7 DNA binding protein. In contrast to the results obtained when DNA synthesis is initiated at single strand breaks in a duplex DNA molecule, essentially none of the DNA synthesized in the presence of T7 RNA polymerase is covalently attached to the T7 DNA template. We postulate that in this in vitro system, T7 DNA replication is initiated using an RNA primer synthesized by the T7 RNA polymerase. PMID- 6249823 TI - Mechanism of hemoglobin oxidation by ferricytochrome c under aerobic and anaerobic conditions. PMID- 6249824 TI - Serological response to formolized Kyasanur forest disease virus vaccine in humans at Sagar and Sorab Talukas of Shimoga district. PMID- 6249825 TI - Cyclic 3',5'-AMP relay in Dictyostelium discoideum III. The relationship of cAMP synthesis and secretion during the cAMP signaling response. AB - Refinement of a perfusion technique permitted the simultaneous measurement of cAMP-elicited [3H]cAMP secretion and intracellular [3H]cAMP levels in sensitive D. discoideum amoebae. These data were compared with measurements of the rate of [32P]cAMP synthesis by extracts of amoebae sonicated at different times during the cAMP signaling response. cAMP stimulation of intact cells led to a transient activation of adenylate cyclase, which was blocked if 10(-4) M NaN3 was added with the stimulus. During responses elicited by 10(-6) M cAMP, 10(-8) M cAMP, and an increment in cAMP from 10(-8) M to 10(-7) M, the rate of cAMP secretion was proportional to the intracellular cAMP concentration. Removal of a 10(-6) M cAMP stimulus 2 min after the initiation of the response led to a precipitous decline in intracellular cAMP. This decline was more rapid than could be accounted for by secretion alone, suggesting intracellular phosphodiesterase destruction of newly synthesized cAMP. Employing these data and a simple rate equation, estimates of the time-course of the transient activation of adenylate cyclase and the rate constants for cAMP secretion and intracellular phosphodiesterase activity were obtained. The calculated rate of cAMP synthesis rose for approximately 1 to 2 min, peaked, and declined to approach prestimulus levels after 3 to 4 min. This time-course agreed qualitatively with direct measurements of the time-course of activation, indicating that the activation of adenylate cyclase is a major in determining the time-course of the cAMP secretion response. PMID- 6249826 TI - Cyclic 3',5'-AMP relay in Dictyostelium discoideum IV. Recovery of the cAMP signaling response after adaptation to cAMP. AB - In dictyoselium discoideum, an increase in extracellular cAMP activates adenylate cyclase, leading to an increase in intracellular cAMP and the rate of cAMP secretion. Cells adapt to any constant cAMP stimulus after several minutes, but still respond to an increase in the concentration of the stimulus. We have now characterized the decay of adaptation (deadaptation) after the removal of cAMP stimuli. Levels of adaptation were established by the perfusion of [(3)H]adenosine-labeled amoebae with a defined cAMP stimulus. After a variable recovery period, the magnitude of the signaling response to a second stimulus was measured; its attenuation was taken as a measure of residual adaption to the first stimulus. The level of adaptation established by the first stimulus depended on both its magnitude and duration. Deadaptation began as soon as the first stimulus was removed. The magnitude of the response to the second stimulus increased with the recovery time in a first-order fashion, with a t(1/2)=3-4 min for stimuli of 10(-8) M to 10(-5) M cAMP. Responses to test stimuli, although reduced in magnitude, had an accelerated time-course when they closely followed a prior response that had not completely subsided. This effect is called priming; we believe it reveals a reversible, rate-limiting step that modulates the onset and termination of the signaling responses of amoebae that have not recently responded to a cAMP stimulus. We have suggested that the cAMP signaling response is controlled by two antagonistic cellular processes, excitation and adaptation. The data reported here imply that both the rate of rise in the adaptation process and the final level reached depend on the occupancy of cAMP surface receptors and that the decay of adaptation when external cAMP is removed proceeds with first order kinetics. PMID- 6249827 TI - Cyclic 3',5'-AMP relay in Dictyostelium discoideum V. Adaptation of the cAMP signaling response during cAMP stimulation. AB - In dictyostelium discoideum, extracellular cAMP activates adenylate cyclase, which leads to an increase in intracellular cAMP and the rate of cAMP secretion. The signaling response to a constant cAMP stimulus is terminated after several minutes by an adaptation mechanism. The time- course of adaptation stimuli of 10( 6) or 10(-7) M cAMP was assessed. We used a perfusion technique to deliver defined cAMP stimuli to [(3)H]adenosine-labeled amoebae and monitored their secretion of [(3)H]cAMP. Amoebae were pretreated with 10(-6) or 10(-7) M cAMP to periods of 0.33-12 minutes, and then immediately given test stimuli of 10(-8) M to 2.5 x 10(-7) M cAMP. The response to a given test stimulus was progressively attenuated and finally extinguished as the duration of the pretreatment stimulus increased. During concentration of the test stimulus. The responses to test stimuli of 10(-8), 5 x 10(-8), 10(-7), or 2.5 x 10(-7) M cAMP were extinguished after approximately 1, 2.25,2.5, and 10 min, respectively. 1.5 min of stimulation with 10(-7) M cAMP was necessary to extinguish the response of a test stimulus of 10(-8) M cAMP. Our data suggest that adaptation begins within 20 s of stimulation, rises rapidly for approximately 2.5 min, and reaches a plateau after approximately 10 min. The absolute rate of rise was faster during pretreatment with 10(-6) than with 10(-7) M cAMP. These results support a working hypothesis in which the occupancy of surface cAMP receptors leads to changes in two opposing cellular processes, excitation and adaptation, that control the activity of D. discoideum adenylate cyclase. PMID- 6249828 TI - Differences between rat liver epithelial and fibroblast cells in metabolism of purines. AB - Epithelial and fibroblast cells from adult rat liver were found to differ markedly in their metabolism of the purine hypoxanthine. Both cell types took up hypoxanthine and possessed hypoxanthine-guanine phosphoribosyl transferase for phosphoribosylating the purine. However, in the transferase assay, lysates from epithelial cells converted hypoxanthine predominantly to inosine monophosphate, with small amounts of the nucleoside inosine as product, whereas fibroblast cell lysates converted hypoxanthine predominantly to inosine. The inosine appeared not to be produced by direct ribosylation of the base, since fibroblast cell lysates had less purine nucleoside phosphorylase activity than epithelial cell lysates. Rather, the inosine produced by fibroblast lysates appeared to be derived from inosine monophosphate through catabolism of the mononucleotide by 5' nucleotidase. An inhibitor of 5' nucleotidase, thymidine triphosphate, reduced the amount of inosine formed. PMID- 6249829 TI - Water permeability of mammalian cells as a function of temperature in the presence of dimethylsulfoxide: correlation with the state of the membrane lipids. AB - The water permeability of V-79 Chinese hamster lung fibroblasts was determined by measuring the rate of cell shrinkage in hypertonic medium using a cell sizer. The water permeability appears to follow Arrhenius kinetics as a function of temperature with a sharp discontinuity at 21 degrees C. An activation energy of 7.0 +/- 1.6 kcal/mole was found below 21 degrees C and 22.8 +/- 3.1 kcal/mole above 21 degrees C. The correlation time of rotation of the spin label 2,2 dimethyl-5-dodecyl-5-methyloxazolidine-N-oxide was measured as a function of temperature in the cellular membranes, and shows a break at 20 degrees C. A discontinuity was also found in the membrane to water partitioning of the spin label 2,2-dimethyl-5-pentyl-5-butyloxazolidine-N-oxide near 20 degrees C. These breaks may correspond to a membrane lipid phase transition. Dimethylsulfoxide, in the concentration range of 0.2--0.5 M, decreases the water permeability by a factor of two. PMID- 6249830 TI - The role of cell swelling and haemolysis in Sendai virus-induced cell fusion and in the diffusion of incorporated viral antigens. AB - The role of the haemolytic activity of Sendai virus in cell-cell fusion has been examined in monolayers of human erythrocytes and erythrocyte ghosts fused with either haemolytic or non-haemolytic virus. Morphological observations indicate that cell swelling and haemolysis is a distinct event in cell-cell fusion irrespective of whether it is virally induced or, in the case of non-haemolytic virus, experimentally induced. Osmotic swelling appears to be the driving force by which cells which have established sites of membrane fusion expand such sites to form poly-erythrocytes. Immunofluorescent labelling of viral antigens incorporated into the erythrocyte membrane as a result of viral envelope-cell fusion indicates that diffusion of antigens in the plane of the membrane is restricted in intact erythrocytes and resealed erythrocyte ghosts but not in haemolysed erythrocytes or unsealed ghosts. A perturbation of the erythrocyte membrane resulting from osmotic lysis appears to form a prerequisite for the lateral diffusion of viral elements. PMID- 6249831 TI - Characterization of a CV-1 cell cycle. II. The role of cell-substrate attachment. AB - The availability of synchronous cultures of untransformed CV-I cells has allowed analysis of the role of cell-substrate attachment in cell cycle progression as well as the ability of serum and SV40 infection to override the requirement for cell-substrate attachment. Attachment to a solid substrate is required for progression through G1. Prevention of attachment results in cell cycle arrest 30 min after cytokinesis. Serum is required for attachment, but increasing the serum concentration from 2 to 20 % does not enhance cell attachment, nor obviate its need for cell cycle progression. SV40 infection does not overcome the requirement of serum for attachment nor the need of attachment for normal cycling. PMID- 6249832 TI - The effect of different treatment regimens on hormonal profiles in congenital adrenal hyperplasia. PMID- 6249833 TI - Serum calcitonin after pentagastrin stimulation in patients with bronchogenic and breast cancer compared to that in patients with medullary thyroid carcinoma. AB - Serum immunoreactive calcitonin (iCT) was measured in the peripheral blood of 29 normocalcemic patients with bronchogenic carcinoma of various pathological types and nine patients with breast cancer before and after pentagastrin stimulation. These results were compared to those found in 22 normal subjects and 30 patients with histologically proven medullary carcinoma of the thyroid. Our results revealed that 1) serum iCT levels may be abnormally high in all pathological types of bronchogenic carcinoma and in patients with breat cancer; 2) the basal level of serum iCT may be normal, but it is abnormally high after pentagastrin stimulation; 3) the increment rise of iCT after pentagastrin stimulation in the bronchogenic and breast cancer patients was significantly less than that seen in patients with medullary carcinoma of the thyroid (P less than 0.001). PMID- 6249834 TI - Adrenocortical 11 beta-hydroxylation defect in adult women with postmenarchial onset of symptoms. AB - Four cases in adults of a deficiency in the 11 beta-hydroxylation of corticosteroids were investigated by both basal and dynamic biological studies. Symptoms varied from patient to patient; hirsutism, menstrual disturbance, acne, deepening of the voice, and arterial hypertension appeared post puberty. Basal testing demonstrated elevated levels of plasma androgens. These include delta 4 androstenedione (patients, 3.80-6.43 ng/ml; normal, 1.33 +/- 0.33 ng/ml), urinary 17-ketosteroids (patients, 11.8-16.7 mg/24 h; normal, 5-10 mg/24 h), and urinary dehydroepiandrosterone. The basal tests were often insufficient to show the accumulation of the precursors (especially 17-hydroxyprogesterone) which are often given as evidence for an increase in ACTH stimulation. In studying the levels of the mineralocorticoids, there was shown to be an increased basal level of tetrahydrodeoxycorticosterone (patients, 142-317 microgram/24 h; normal, 60-80 microgram/24 h) which was raised by ACTH stimulation. These results, therefore, confirm the characteristic partial enzyme defect and give evidence for the heterogeneity of this syndrome. Based on the above observations, we believe it is appropriate to rename this condition adult adrenocortical 11 beta-hydroxylation defect rather than late-onset congenital adrenal hyperplasia. PMID- 6249835 TI - The mechanism of the suppressive action of bromocriptine on adrenocorticotropin secretion in patients with Cushing's disease and Nelson's syndrome. PMID- 6249836 TI - Sensitization of T-lymphocytes in Graves' and Hashimoto's diseases. PMID- 6249837 TI - Effect of growth hormone administration: reciprocal changes in serum 1 alpha,25 dihydroxyvitamin D and intestinal calcium absorption. AB - The mechanism by which GH stimulates intestinal calcium absorption was explored. In this study, seven children with idiopathic GH deficiency were studied before and during GH therapy while they were maintained on the same metabolic diet. After 5-14 months of GH administration, fractional intestinal calcium absorption increased from 0.364 +/- 0.114 to 0.449 +/- 0.159 (P less than 0.01), and serum 1,25-dihydroxyvitamin D decreased from 63.7 +/ 19.3 to 46.7 +/ 17.8 pg/ml (P less than 0.025). Serum immunoreactive parathyroid hormone, urinary cAmp, serum 24,25-dihydroxyvitamin D, and 25-hydroxyvitamin D did not change significantly. The data suggest that GH does not directly influence parathyroid hormone or vitamin D metabolism. The possibility that relative intestinal resistance to 1,25 dihydroxyvitamin D exists in patients with GH deficiency is considered. PMID- 6249838 TI - Pubertal presentation of congenital delta 5-3 beta-hydroxysteroid dehydrogenase deficiency. PMID- 6249839 TI - Chemical characterization of adrenocorticotropin and a novel peptide biosynthesized from a pituitary adenoma of a patient with Cushing's disease. AB - ACTH and another unidentified peptide have been biosynthesized in vitro and purified from a pituitary adenoma of a patient with Cushing's disease. The new peptide had an apparent molecular weightof 4000 daltons and was more acidic than ACTH as analyzed by sodium dodecyl sulfate/urea and acidic (pH 4.5) polyacrylamide gel electrophoreses, respectively. Sequence studies revealed the presence of [35S]methionine at position 3 of the new peptide. High performance liquid chromatographic analysis of [35S]methionine-labeled tryptic fragments of the peptide revealed that this peptide contained gamma MSH- (1-7) within its sequence. Our observations raise the possibility that this peptide contains at its N-terminus gamma MSH, a putative peptide proposed by Nakanishi et al. PMID- 6249840 TI - Compartmentalization of human growth hormone by cultured human lymphocytes. PMID- 6249841 TI - The distribution of forms of adrenocorticotropin and beta-endorphin in normal, tumorous, and autopsy human anterior pituiary tissue: virtual absence of 13K adrenocorticotropin. AB - To begin to define the nature of the biosynthesis and processing of ACTH and beta endorphin in the human, anterior pituitary tissue (fresh normal and adenomatous, and autopsy) was extracted in acetic acid in the presence of protease inhibitors and subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The gel slice eluates were assayed for ACTH and beta-endorphin immunoactivity. Human anterior pituitary tissue contained four major size classes of ACTH and three major size classes of beta-endorphin. We found that in all tissue sources examined there was a virtual absence of 13-15K ACTH, which is a major form in the rat and mouse. When comparing extracts obtained from fresh normal or adenomatous anterior pituitary tissue, we also found a drastic decrease in beta-lipotropin and beta-endorphin in extracts of autopsy human anterior pituitaries. These results suggest that the biosynthesis and processing of pituitary ACTH and beta endorphin in the human may be different than in the mouse, and because of apparent postmortem proteolysis of beta-endorphin, human pituitary obtained at autopsy is probably not a good source of material for biochemical studies of pituitary tissue. PMID- 6249842 TI - Testicular GnRH receptors--characterization and localization on interstitial tissue. AB - Testicular GnRH membrane receptors were demonstrated using the non-degradable GnRH analog D-Ala6des-Gly10 GnRH ethylamide (D-Ala6) as ligand. Displaceable 125I D-Ala6 binding was present on crude membranes prepared from whole testes and interstitial tissue but not on the fractions from seminiferous tubules. 125I D Ala6 binding to interstitial tissue was specific as only unlabeled D-Ala6 analog and synthetic GnRH inhibited binding of D-Ala6 tracer. Scatchard analysis of the analog data revealed a single high affinity binding site (Ka = 7 x 10(9) M-1) with a binding capacity of 200 +/- 10 (SE) fmol/mg membrane protein. In vivo treatment of both intact and hypophysectomized adult male rats with synthetic GnRH (6.6 microgram every 8 hr for 3 days) resulted in a 2-fold increase in GnRH binding capacity without change in receptor affinity. These results indicate that specific high affinity GnRH receptors are present only on interstitial tissue membrane fractions and receptor numbers are increased by a direct action of GnRH on the testis. PMID- 6249843 TI - Cellular action of vasopressin in medullary tubules of mice with hereditary nephrogenic diabetes insipidus. AB - Our previous studies (1974. J. Clin. Invest.54: 753-762.) suggested that impaired metabolism of cyclic AMP (cAMP) may be involved in the renal unresponsiveness to vasopressin (VP) in mice with hereditary nephrogenic diabetes insipidus (NDI). To localize such a defect to specific segments of the nephron, we studied the activities of VP-sensitive adenylate cyclase, cAMP phosphodiesterase (cAMP-PDIE), as well as accumulation of cAMP in medullary collecting tubules (MCT) and in medullary thick ascending limbs of Henle's loop (MAL) microdissected from control mice with normal concentrating ability and from mice with hereditary NDI. Adenylate cyclase activity stimulated by VP or by NaF was only slightly lower ( 24%) in MCT from NDI mice, compared with controls. In MAL of NDI mice, basal, VP sensitive, and NaF-sensitive adenylate cyclase was markedly (> -60%) lower compared with MAL of controls. The specific activity of cAMP-PDIE was markedly higher in MCT of NDI mice compared with controls, but was not different between MAL of control and NDI mice. Under present in vitro conditions, incubation of intact MCT from control mice with VP caused a striking increase in cAMP levels (>10), but VP failed to elicit a change in cAMP levels in MCT from NDI mice. When the cAMP-PDIE inhibitor 1-methyl-3-isobutyl xanthine (MIX) was added to the above incubation, VP caused a significant increase in cAMP levels in MCT from both NDI mice and control mice. Under all tested conditions, cAMP levels in MCT of NDI mice were lower than corresponding values in control MCT. Under the present experimental setting, VP and other stimulating factors (MIX, cholera toxin) did not change cAMP levels in MAL from either control mice or from NDI mice. The results of the present in vitro experiments suggest that the functional unresponsiveness of NDI mice to VP is perhaps mainly the result of the inability of collecting tubules to increase intracellular cAMP levels in response to VP. In turn, this inability to increase cAMP in response to VP is at least partly the result of abnormally high activity of cAMP-PDIE, a somewhat lower activity of VP sensitive adenylate cyclase in MCT of NDI mice, and perhaps to a deficiency of some other as yet unidentified factors. The possible contribution of low VP sensitive adenylate cyclase activity in MAL of NDI mice to the renal resistance to VP remains to be defined. PMID- 6249844 TI - Effect of D-alanine methionine enkephalin amide on ion transport in rabbit ileum. AB - The presence of enkephalins in the intestine and the use of opiates to treat diarrheal diseases suggests that enkephalins may affect intestinal ion transport. Using isolated rabbit ileal mucosa, we found that leucine enkephalin, methionine enkephalin, and D Ala2-methionine enkephalin amide (D Ala2-Met E) decreased the short circuit current (Isc) and potential difference although the effect of D Ala2-Met E was more pronounced and prolonged. D Ala2-Met E increased net sodium (+1.27 +/- 0.5 mu eq/cm2h), and chloride absorption (+2.33 +/- 0.4), and increased tissue conductance by 37%. Although the effect of enkaphalin on ion transport is opposite that of cyclic AMP, D-Ala2-Met had no effect on basal or vasoactive intestinal polypeptide-stimulated cyclic AMP levels. The effect of D Ala2-Met E on Isc was blocked by naloxone, suggesting the involvement of specific opiate receptors. Tetrodotoxin completely blocked the decrease in Isc induced by D-Ala2-Met E but not by epinephrine, inferring that enkephalins are preganglionic neurotransmitters. The effect of D-Ala2-Met E on Isc was not blocked by phentolamine, haloperidol, or pretreatment of animals with 6-hydroxydopamine, suggesting that enkephalin does not affect the Isc by stimulating the release of alpha-adrenergic or dopaminergic agonists. D-Ala2-Met E also decreased the Isc in the presence of carbachol and bethanechol, indicating that enkephalin does not inhibit the release of acetylcholine. Further, up to 10 mu M atropine had no effect on the Isc. These studies demonstrate that enkephalins stimulate intestinal ion transport and may do so by stimulating (or inhibiting) the release of a nonadrenergic, noncholinergic neurotransmitter. PMID- 6249845 TI - Multiple enzymatic defects in mitochondria in hematological cells of patients with primary sideroblastic anemia. AB - Activities of mitochondrial enzymes in blood cells from 69 patients with primary sideroblastic anemia were determined to elucidate the pathogenesis of the disease. In erythroblasts of patients with primary acquired type the activities of both delta-aminolevulinic acid synthetase and mitochondrial serine protease were inevitably decreased. The susceptibility to the protease of apo-delta aminolevulinic acid synthetase prepared from erythroblasts of patients with this type was within the normal range, in contrast to that of pyridoxine-responsive anemia. The activities of mitochondrial enzymes such as cytochrome oxidase, serine protease, and oligomycin-sensitive ATPase, except citrate synthetase, were usually decreased in mature granulocytes of the patients. Patients with hereditary sideroblastic anemia also had decreased delta-aminolevulinic acid synthetase activity in erythroblasts, and decreased serine protease activity in both erythroblasts and mature granulocytes. Mature granulocytes obtained from patients with pyridoxine-responsive anemia before therapy had decreased cytochrome oxidase activity, however, the activity increased to a normal level when the patients were in remission. The activities of other mitochondrial enzymes in mature granulocytes were within normal range in these patients before pyridoxine therapy. The activities of these mitochondrial enzymes in lymphocytes were within normal range in all groups of patients with primary sideroblastic anemia. We suggest that patients with primary acquired, and possibly also those with hereditary sideroblastic anemia have impaired mitochondrial function in both erythroblasts and granulocytes. That only anemia is observed in these patients is because a functional abnormality of mitochondria in erythroblasts is most important because of the role of mitochondria in the formation of heme in erythrocyte development. In contrast to these two types of sideroblastic anemia, only delta-aminolevulinic acid synthetase in both erythroblasts and granulocytes seems to be impaired in patients with pyridoxine-responsive anemia. PMID- 6249846 TI - Enhancement of neutrophils function as a result of prior exposure to chemotactic factor. AB - Exposure of human polymorphonuclear leukocytes (PMN) to chemotactic factor, as well as the migration of PMN through a 5-mum pore-size membrane, results in a PMN population with enhanced chemiluminescence, enhanced capacity for superoxide anion production, and increased Escherichia coli bactericidal activity. The enhanced PMN response resulting from exposure to chemotactic factor was observed with several chemotactic stimuli, including a mixture of casein and autologous serum, chemotactic C5 fragment, and formyl-l-methionyl-l-leucine-l-phenylalanine (f-Met-Leu-Phe). Enhanced levels of chemiluminescence were observed with both soluble stimuli (concanavalin A and phorbol myristate acetate) as well as particulate stimuli (opsonized zymosan). Once activated by chemotactic factor, PMN retained their enhanced stimulated chemiluminescence in the absence of chemotactic factor for at least 2.5 h. Enhanced activity could not be correlated with a shift in the number of immunoglobulin (Ig)G Fc receptor positive or complement receptor positive PMN. In vivo studies with guinea pigs indicated that PMN attracted to an intraperitoneal injection of casein, like those attracted through a chemotaxis membrane in vitro in response to casein, showed markedly enhanced stimulated chemiluminescence when compared with peripheral blood PMN from the same animal. Such a mechanism to stimulated PMN function may enhance the effectiveness of PMN in host defense at inflammatory foci. PMID- 6249847 TI - Enhanced biosynthesis of human skin collagenase in fibroblast cultures from recessive dystrophic epidermolysis bullosa. AB - Using a sensitive, specific immunoprecipitation method, the biosynthesis of human skin collagenase was studied in fibroblast cultures from patients with recessive dystrophic epidermolysis bullosa. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of solubilized immunoprecipitates showed two 3H-labeled procollagenase species that comigrated with those harvested from control cultures. Recessive dystrophic epidermolysis bullosa cultures accumulated increased amounts of collagenase. Both the initial rate of accumulation of intracellular enzyme and the rate of secretion were enhanced, suggesting that excessive accumulation is related to increased synthesis. Because the turnover of labeled collagenase was unaltered, the accumulation could not be attributed to diminishing enzyme degradation. No preferential incorporation of [3H]leucine into recessive dystrophic epidermolysis bullosa collagenase occurred. Furthermore, the mutant cultures displayed no alteration in total protein synthesis, the intracellular leucine pool, or the growth kinetics of the cells. Cells from a patient with dominant epidermolysis bullosa did not show enhanced accumulation of collagenase. The levels of collagenase synthesized in vitro correlated with those observed previously in vivo in recessive dystrophic epidermolysis bullosa patients, suggesting that this biochemical trait is pathogenetically significant in the disorder. PMID- 6249848 TI - Diminished polymorphonuclear leukocyte adherence. Function dependent on release of cyclic AMP by endothelial cells after stimulation of beta-receptors by epinephrine. AB - To investigate the biochemical and cellular basis for the rise in polymorphonuclear leukocyte (PMN) count during epinephrine administration, PMN from subjects receiving epinephrine were studied for their capacity to adhere to nylon wool fibers and endothelial cell monolayers. After administration of epinephrine, the PMN count increased by 80% at 5 min, and isolated PMN adherence to nylon fibers fell from a base line of 44+/-2-18+/-3%. In contrast, when subjects were infused with the beta-antagonist propanolol before receiving epinephrine, the PMN count failed to rise and PMN adherence was normal. Exposure of PMN endothelial cell monolayers to 0.1 muM epinephrine led to diminished PMN adherence that could be blocked by 10 muM propanolol but not by 10 muM phentolamine. Sera obtained from subjects 5 min after receiving epinephrine or from supernates derived from endothelial cell monolayers exposed to 90 nM epinephrine inhibited PMN adherence to nylon fibers. Addition of anticyclic AMP antisera but not anticyclic guanosine monophosphate antisera to the postepinephrine sera or to the postepinephrine supernate derived from the endothelial cell monolayers abolished their inhibitory effect of PMN adherence to nylon fibers. In contrast, direct exposure of PMN to epinephrine failed to affect their adherent properties. Because it has been previously shown that endothelial cells contain beta-receptors and respond to catecholamines by raising their intracellular concentrations of cyclic AMP, and that PMN adherence is attenuated by cyclic AMP, it would appear that diminished PMN adherence after epinephrine administration is mediated through endothelial cell beta-receptor activity, which in turn impairs PMN margination in vivo and could account for the rise in circulating PMN. PMID- 6249849 TI - Calcium dependence of serotonin-induced changes in rabbit ileal electrolyte transport. AB - These studies describe the calcium dependence of the serotonin-induced changes in active electrolyte transport in rabbit ileum in vitro. In the presence of a standard calcium concentration (1.2 mM) in the serosal bathing fluid, serosal serotonin caused a transient increase in short-circuit current and a prolonged decrease in net Na and Cl fluxes. Removing calcium from the serosal (no calcium plus 1 mM EGTA) but not the mucosal bathing fluid inhibited the serotoin-induced increase in ileal short-circuit current, and also completely blocked the serotonin effects on net Na and net Cl fluxes. This inhibition was rapidly reversed by readding calcium. Removing serosal calcium did not inhibit all active electrolyte transport processes, as the effect of a maximum concentration of theophylline (10 mM) was not altered. Similarly, d,l-verapamil, a calcium channel blocker, inhibited the serotonin-induced changes in short-circuit current and in net Na and net Cl fluxes, but did not alter the theophylline effects. In contrast, d-verapamil, a stereoisomer which does not block calcium channels, did not inhibit the serotonin-induced changes. The calcium dependence of these serotonin effects was associated with increased uptake of 45Ca into rabbit ileum, including increaed 45Ca uptake from the serosal surface. Serotonin also increased the rate of 45Ca efflux from rabbit ileum into a calcium-free solution, compatible with serotonin increasing the ileal plasma membrane permeability to calcium. It is postulated that serotonin affects active intestinal electrolyte transport by a mechanism dependent on serosal but not mucosal calcium that involves an increase in the intestinal plasma membrane permeability to calcium, and perhaps an increase in intracellular calcium. PMID- 6249850 TI - B cell differentiation and immunoregulatory T cell function in human cord blood lymphocytes. AB - The functional maturity of T and B lymphocyte populations from human newborns was evaluated using a reverse hemolytic plaque assay to detect immunoglobulin secreting cells generated in in vitro cultures stimulated with pokeweed mitogen (PWM), a T cell-dependent polyclonal activator, and the Epstein-Barr virus (EBV), a T cell-independent B cell activator. Cord blood lymphocytes failed to produce immunoglobulin in response to PWM, but did respond with immunoglobulin synthesis to stimulation with EBV. Co-culture experiments demonstrated that cord blood T cells would inhibit immunoglobulin production by adult cells stimulated with PWM, but not with EBV. Cord blood T cells did suppress immunoglobulin production by cord blood B cells when stimulated with a mixture of EBV and PWM, indicating that cord blood, in contrast to adult blood, contains a population of suppressor T cell precursors that are easily activated by PWM. Irradiation of the cord blood T cells with 2,000 rad eliminated the suppressor activity and revealed normal helper function for immunoglobulin (Ig) G, A, and M when these T cells were co cultured with adult B cells. Cord blood B cells co-cultured with adult T cells or irradiated cord blood T cells did produce immunoglobulin in response to PWM, but the response was significantly lower than that of adult B cells, and only IgM was produced in these cultures. These studies demonstrate that both the T and B cells of the human newborn have significant functional differences compared with the functions of T and B lymphocyte populations in adults. PMID- 6249851 TI - Use of lipophilic probes of membrane potential to assess human neutrophil activation. Abnormality in chronic granulomatous disease. AB - Previous studies using membrane potential sensitive probes have provided evidence that chemotactic factors elicit membrane potential changes in normal human neutrophils (PMN). In addition to stimulation of PMN motility, chemotactic factors also stimulate degranulation and superoxide ion (O-2) generation and it has been suggested that alteration of membrane potential activates these events (Korchak, H. M., and G. Weissmann. 1978. Proc, Natl, Acad, Sci. U. S. A. 75: 3818 -3822). To further define the inter-relationship of these functions, studies were done with two indirect probes of membrane potential, 3-3'-dipentyloxacarbocyanine and triphenylmethylphosphonium ion (TPMP+) using PMN from normal subjects, from patients with abnormal O-2 production (chronic granulomatous disease [CGD]), and from patients with defective degranulation and/or chemotaxis (Cheddiak-Higashi syndrome and patients with elevated immunoglobulin (Ig)E and recurrent staphylococcal infections). The stimuli used were the chemoattractant N-formyl methionyl-leucyl-phenylalanine (f-Met-Leu-Phe) and the secretagogues ionophore A23187 and phorbol myristate acetate (PMA). The results obtained with 3-3' dipentyloxacarbocyanine and TPMP+ were comparable. The apparent membrane potential changes elicited by f-Met-Leu-Phe and PMA in normal PMN were reduced or entirely absent in PMN obtained from patients with CGD but normal in PMN from other patients. PMN from patients with CGD had normal calculated resting membrane potentials and normal responses elicited by the potassium ionophore valinomycin. The responses to calcium ionophore A23187 were only slightly impaired. The abnormality of the elicited response of CGD cells of f-Met-Leu-Phe and PMA could not be attributed to the absence of O-2, hydroxyl radical, singlet oxygen, or hydrogen peroxide acting on the probes. Instead this abnormality appears to be associated with a dysfunction in the normal molecular mechanism(s) stimulated upon neutrophil activation. The data suggest chemoattractant alteration of membrane potential in normal PMN is related to activation of oxidative metabolism but the relationship to chemotaxis and degranulation remains to be established. PMID- 6249852 TI - Effect of thyroid status on insulin action in rat adipocytes and skeletal muscle. AB - Isolated adipocytes and soleus muscles prepared from mature rats, rendered hypothyroid by a low iodine diet and propylthiouracil, markedly resisted the ability of insulin to increase glucose utilization. In adipocytes, the sum of basal d-(1-(14)C)-glucose conversion to CO(2), glyceride-glycerol, and fatty acid was unaltered by hypothyroidism, although conversion to fatty acid was decreased. The response of each of these metabolic pathways to insulin at all concentrations tested was greatly diminished in hypothyroid rat adipocytes. 3-O-Methylglucose transport rates in the presence of insulin were not significantly different in adipocytes from hypothyroid as compared with euthyroid rats, although basal transport rates were significantly higher in the hypothyroid state. Lipolysis and cyclic AMP accumulation in adipocytes from hypothyroid rats in response to theophylline were markedly diminished compared with euthyroid controls, but insulin was about as effective in inhibiting lipolysis in these cells as in those derived from euthyroid animals. The binding of (125)I-insulin to adipocytes at several hormone concentrations was also shown to be unaffected by hypothyroidism. In soleus muscle, basal glucose conversion to H(2)O and glycogen was unaltered in the hypothyroid state, whereas insulin action on these pathways was markedly inhibited. The decrease in muscle insulin responsiveness was less marked than that observed in adipocytes. Uptake of either 2-deoxyglucose or l-arabinose in the presence or absence of insulin was similar in soleus muscles derived from euthryoid vs. hypothyroid rats. Similarly, insulin action on the conversion of soleus muscle glycogen synthase D to the I form in the absence of glucose was unaltered by hypothyroidism. We conclude that (a) hypothyroidism in mature rats leads to a marked decrease in the responsiveness of glucose metabolism in adipocytes and skeletal muscle to insulin; (b) no detectable impairment of the membrane insulin effector systems that mediate the regulation of adipocyte hexose transport and glycogen synthase is caused by hypothyroidism in this animal model; and (c) the cellular defect that leads to apparent insulin resistance of adipocyte and soleus muscle glucose utilization resides at the level of one or more intracellular enzymes involved in glucose catabolism. PMID- 6249853 TI - Chronic granulomatous disease. Expression of the metabolic defect by in vitro culture of bone marrow progenitors. AB - Chronic granulomatous disease (CGD), an often fatal syndrome of recurrent infections results from the inability of patients' peripheral blood phagocytic leukocytes to generate superoxide despite otherwise normal phagocytic functions such as ingestion and degranulation. Circulating granulocytes and monocytes are the progeny of bone marrow progenitor cells, colony-forming units in culture. We compared the function of cells grown in two different in vitro cuture systems from the bone marrow of a CGD patient with those from normal subjects. The cells of normal colony-forming unit in culture colonies grown in semisolid medium reduced nitroblue tetrazolium dye when stimulated by phorbol myristate acetate; none of the cells from colonies derived from CGD marrow did so. Cells grown in liquid suspension culture from normal marrow generated superoxide nearly as well as normal peripheral blood granulocytes; those from CGD marrow produced no superoxide, similarly cultured cells from both normal and CGD marrow ingested opsonized bacteria at rates equal to peripheral blood granulocytes. CGD marrow derived cells showed increased exocytic degranulation relative to both normal marrow-derived cells and normal peripheral blood granulocytes. These studies demonstrate that the basic functional characteristics of CGD are embedded in the genetic program of granulocyte progenitors. PMID- 6249854 TI - Extrarenal Wilms' tumor: sonographic appearance. PMID- 6249855 TI - Synergistic haemolysis test for presumptive identification and differentiation of Clostridium perfringens, C. bifermentans, C. sordellii, and C. paraperfringens. AB - A new test for the presumptive identification of Clostridium perfringens, C. bifermentans, C. sordellii, and C. paraperfringens is described. The test is based on the synergistic haemolysis shown by the clostridia and group B streptococci on sheep and human and CaCl2-supplemented human blood agar. C. perfringens gave crescent-shaped synergistic lytic zones (7 to over 20 mm in length), and C. paraperfringens usually small-sized (3 mm), bullet-shaped reactions on all three types of media. C. bifermentans showed a horseshoe-shaped synergistic reaction only on human blood containing media, and C. sordellii only on CaCl2-supplemented human blood agar. C. perfringens type A antiserum inhibited synergistic lytic activities of the four species. The test provided a reliable method for presumptive identification and differentiation of the four clostridial species and may obviate the need for the Nagler test. PMID- 6249856 TI - Comparison of electron microscopy and immunofluorescence in cell culture for rotavirus detection. PMID- 6249857 TI - Biochemical findings in sarcoidosis. AB - The majority of patients with sarcoidosis in this large series have had a number of biochemical investigations performed. Abnormal calcium metabolism was demonstrated in 40% of the patients but permanent renal damage due to nephrocalcinosis as a result of persistent derangement of calcium metabolism was rare. Raised immunoglobulin levels were seen. Half the white and two-thirds of the West Indian patients had elevated IgG levels. Abnormal immunoglobulin levels carried no obvious diagnostic or prognostic significance. Raised alkaline phosphatase levels reflected space-occupying hepatic granulomas and occurred in 23% of patients. Serum angiotensin converting enzyme (SACE) was elevated in half the patients. The highest SACE activity was found in patients with severe parenchymal lung infiltration due to sarcoidosis, and the lowest levels in those with inactive disease or after successful management with steroid drugs. SACE levels were not significantly elevated in four other granulomatous conditions: Crohn's disease, primary biliary cirrhosis, Hodgkin's disease, and active tuberculosis. PMID- 6249858 TI - Comparison of methods available for assay of chloramphenicol in clinical specimens. AB - Eight methods for the assay of chloramphenicol in clinical samples were compared with our own modification of a plate diffusion technique using Sarcina lutea and yeast extract agar. Six of the eight methods were less sensitive than originally reported, and five of them were considered unsuitable for use in clinical microbiology practice. The remaining three methods together with the S. lutea/yeast extract modification were used to assay chloramphenicol in 20 samples of serum. Twenty samples of cerebrospinal fluid were also assayed by the S. lutea/yeast extract method. Our results indicate that only the Bacillus subtilis (sensitivity 6x0 mg/l) and the S. lutea (sensitivity 2x5 mg/l) diffusion methods are suitable for use with clinical samples in routine practice. The problems of chloramphenicol toxicity, appropriate dosage regimens, and the need for assay of the drugs are considered. PMID- 6249859 TI - Ketoconazole--an oral antifungal with activity against superficial and deep mycoses. International Symposium, Medellin, Colombia, Nov. 28 and 29, 1979. PMID- 6249860 TI - Fate of isotopically labeled cholecalciferol and 25-hydroxycholecalciferol in sheep. AB - The fate of tritiated 25-hydroxycholecalciferol administered intramuscularly is compared in two groups of sheep raised either in confinement or outdoors. The uptake of radioactivity was more rapid by the indoor than the outdoor sheep. The assessment of radioactivity in plasma and tissues of outdoor sheep dosed with either tritiated 25-hydroxycholecalciferol or with equivalent amounts of tritiated cholecalciferol revealed that plasma and tissue radioactivity were substantially higher in sheep dosed with tritiated 25-hydroxycholecalciferol than in sheep dosed with tritiated cholecaliferol. Three days after the administration of tritiated cholecalciferol virtually all plasma radioactivity was associated with 25-hydroxycholecalciferol. PMID- 6249861 TI - Calcium and cGMP in isolated rat parotid acinar cells. AB - The role of calcium ions in the activation of guanylate cyclase and in the propagation of the effects of cGMP during activation of the muscarinic cholinergic receptors was studied in isolated rat parotid acinar cells. It was demonstrated that the requirement for extracellular calcium is complete in the transduction of information from the muscarinic receptor to the guanylate cyclase, and partial in the steps beyond the synthesis of cGMP. PMID- 6249862 TI - Orientations of carbonate ions in human tooth enamel studied with use of the CO3 3 radical ions as probes. AB - With the use of CO3-3 radical ions as probes, it is concluded that the carbonate ions substitute in the apatite lattice of human tooth enamel in two different ways. Most of the carbonate ions in the apatite lattice are aligned with their symmetry axis parallel to the c axis, whereas the remaining carbonate ions are aligned with their symmetry axis perpendicular to the c axis. PMID- 6249863 TI - Chemotaxis. PMID- 6249864 TI - Reduced aldosterone secretory response to acute ACTH stimulation in sodium restricted elderly subjects. PMID- 6249865 TI - [Ocular infection caused by adenovirus 19 (author's transl)]. AB - A case of ocular infection due to adenovirus type 19 is reported. The patient developed a bilateral keratoconjunctivitis with preauricula nodes and a mild general malaise. The virus was isolated from both eyes; serological tests carried out on the serum of the patient were compatible with the diagnosis. PMID- 6249866 TI - Reaction of solid carrier-adsorbed polycyclic aromatic hydrocarbons with gaseous low-concentrated nitrogen dioxide. AB - The interaction of gaseous NO2 with solid carrier-adsorbed polycyclic aromatic hydrocarbons was studied under laboratory conditions with a specific attention to factors that might possibly influence this reaction, such as type of carrier lighting conditions, NO2 concentration, exposure time, and temperature. At the NO2 concentration of 1.33 ppm there were detected the following nitro derivatives: nitroanthracene, nitropyrene, nitrochrysene, two mononitro derivatives of benzo/a/pyrene, and dinitrobenzo/a/pyrene. The experimental data suggest that the formation of nitroaromates in atmospheric environment is to be expected, provided that there are present, besides polycyclic aromatic hydrocarbons and nitrogen oxides, also suitable types of sorbents, such as silica gel or fly ash. PMID- 6249867 TI - Detection of antibodies against foot-and-mouth disease virus using purified Staphylococcus A protein conjugated with alkaline phosphatase. AB - Purified protein A (PA) from Staphylococcus aureus was conjugated with the enzyme alkaline phosphatase. This reagent reacted well with pig, rabbit and guinea pig IgG and less well with mouse and bovine IgG. Radioactive 125I-labelled PA showed a similar affinity for the IgGs examined. Antibodies against foot-and-mouth disease virus contained in guinea pig, rabbit and pig serum were detected, using the enzyme-conjugated PA in indirect tests, which were of similar sensitivity to those using enzyme-conjugated anti-species antibody as tracer. PMID- 6249868 TI - [Clear cell sarcoma of the kidney in the child]. PMID- 6249869 TI - A prospective study of human polyomavirus infection in pregnancy. AB - Urine samples from 1,235 pregnant women were examined by light microscopy for cytologic evidence of virus infection. Smears of urine sediment from 40 women (3.2%) were observed to contain inclusion-bearing cells; polyomavirus infection was confirmed by virologic methods in 24 (60%). A polyomavirus was isolated from 12 women. Five isolates were identified as JC virus and one as BK virus. Another isolate designated AS virus appeared to be unique. Serologic studies on the 40 women were consistent with a high frequency of reactivation of JC virus, and virus excretion was related to gestation. The evidence suggests that selective excretion of JC virus may occur in pregnancy. Among 390 pregnant women without inclusion-bearing cells in their urine, 78 (20%) had a high or rising titer of serum antibody to JC or BK virus or both, a result suggesting virus reactivation, but virus excretion was not detected. In contrast to other reports, no evidence was found for transmission of BK virus to the fetus. PMID- 6249870 TI - Microneutalization of cytomegalovirus. AB - A simple microneutralization test for cytomegalovirus (CMV) is presented. Using a laboratory adapted stock virus, definite results were obtained after 10 days. All patients with primary CMV infection showed an antibody rise and/or seroconversion; however, neutralizing antibody appeared only seven weeks after the onset of clinical symptoms. In control patients without evidence of recent primary infection, there was a complete concordance of the presence of complement fixing and neutralizing antibodies. PMID- 6249871 TI - Sequential outbreaks of infection due to Klebsiella pneumoniae in a neonatal intensive care unit: implication of a conjugative R plasmid. AB - Sequential outbreaks of infection in a neonatal intensive care unit were due to multiple antibiotic-resistant strains of Klebsiella pneumoniae of different serotypes. In investigations of these outbreaks, the transfer of resistance to gentamicin, ampicillin, cephalothin, carbenicillin, and kanamycin from gentamicin resistant organisms to standard laboratory recipients and between recipients was observed. Purified plasmid DNA, isolated from all multiple antibiotic-resistant strains, was analyzed by agarose gel electrophoresis, which revealed a common, large plasmid component with a molecular size of 71 megadaltons. Analysis of drug resistant progeny suggested this plasmid encoded resistance to antibiotics and the information needed for its transmission. The identity of the plasmid from three different sources was established by the use of restriction-enzyme fingerprinting. The dissemination and persistence of this plasmid in environmental and fecal organisms, despite the disappearance of multiple antibiotic-resistant K. pneumoniae, provided a potential source for spread to other bacteria. PMID- 6249872 TI - Killing of virus-infected cells by cytotoxic lymphocytes. PMID- 6249873 TI - Bordetella pertussis respiratory tract infection in the mouse: pathophysiological responses. AB - The influence of living Bordetella pertussis on the induction and duration of pathophysiological reactions in mice infected intranasally with graded doses of culture was studied. Lethally infected mice showed loss of body weight, spleen atrophy, pronounced hypothermia and hypoglycemia, and highly elevated levels of leukocytes and serum immunoreactive insulin. Sublethally infected mice showed normal weight gain, practically normal temperature, spleen enlargement, lesser pronounced hypoglycemia, lower but significantly elevated levels of leukocytes and serum immunoreactive insulin, and histamine sensitization. Intensity of each reaction was related to the degree of lung infectivity. Hypothermia and leukocytosis were highly correlated. Concentration of serum immunoreactive insulin was closely related to the level of leukocytosis but not to the level of glucose. The strain and age of mice significantly affected the degree and duration of the reactions. The results suggest that the intranasally infected mouse may provide a useful model for investigations on whooping cough. PMID- 6249874 TI - An in vitro model for investigation of chemotherapeutic agents in leishmaniasis. AB - Clinically achievable concentrations of the three major antileishmanial drugs in use--pentavalent antimony, pentamidine, and amphotericin B--eliminated 90%--100% of the mammalian forms (amastigotes) of Leishmania tropica and Leishmania donovani from in vitro infected human monocyte-derived macrophages. This is apparently the first report of in vitro susceptibility of Leishmania to pentavalent antimony or to pentamidine. The insensitivity of insect forms (promastigotes) multiplying in cell-free media to thee drugs suggests that amastigotes are more sensitive than promastigotes to these antileishmanial agents. Alternatively, macrophages may concentrate or metabolize the drugs to increase their toxicity. In contrast, amphotericin B was toxic to both amastigotes and promastigotes. The sensitivities of Leishmania within human monocyte-derived macrophages in vitro to clinically achievable concentration of antileishmanial agents suggests that this model may be useful for investigation of mechanisms of sensitivity and resistance of antimicrobial agents against Leishmania. PMID- 6249875 TI - Cytomegalovirus infection in patients with renal transplants: potentiation by antithymocyte globulin and an incompatible graft. AB - Fifty-six of 67 patients with antibody to cytomegalovirus before transplantation shed cytomegalovirus from urine and/or saliva postoperatively. Symptomatic reactivation occurred in 17 (25%) patients, five of whom had pneumonitis. The symptomatic patients were more likely to have received a cadaver kidney (P = 0.004) and high-dosage antithymocyte globulin (P = 0.003) and to be viremic (P < 0.0001), compared to patients with silent infection. Forty-eight of 49 patients treated with antithymocyte globulin received cadaver or parent donor kidneys. Twenty-four were given a low-dosage intramuscular regimen, and 25 received a higher dosage intravenously. In the latter group 48% experienced symptomatic reactivation adn 48% viremia, compared to 21% and 17%, respectively, in the former group (P < 0.05 for both comparisons). There were no symptomatic cytomegaloviral infections among 18 patients not treated with antithymocyte globulin, all of whom received related donor kidneys. Renal transplant patients who receive both a poorly matched graft and antithymocyte globulin are at increased risk of morbidity due to cytomegalovirus. PMID- 6249876 TI - Connective tissue activation. XVIII. Stimulation of hyaluronic acid synthetase activity. AB - Human synovial fibroblasts synthesize hyaluronic acid, a process that can be stimulated by a number of agents. Several steps in the synthetic pathway could be the locus at which these stimulators act; the final step, promoted by hyaluronic acid synthetase, was selectd for study. Hyaluronic acid synthetase is an enzyme system that transfers monosaccharide units to nascent hyaluronic acid chains. Activities of the enzyme were determined in lysates of cultured synovial fibroblasts by measuring incorporation of 14C-UDP-glucuronic acid into hyaluronic acid. Rates of hyaluronic acid synthesis were increased by adding CTAP-I or CTAP III, DbcAMP, or prostaglandin E2 to the cultures. In each instance, hyaluronic acid synthetase activity was enhanced in a manner comparable to that seen in hyaluronic acid synthesis. The changes in enzyme and product were observed as early as 6 hr after cultures were exposed to CTAP-III, and both indices declined when this stimulator was withdrawn for 24 hr. Although DbcAMP incrased the hyaluronic acid synthetase activity of intact fibroblasts, it had no effect on the enzyme in lysates of cells. In the cultured cells, cycloheximide reduced basal levels of synthetase activity and hyaluronic acid synthesis of hyaluronic acid may do so by inducing hyaluronic acid synthetase. PMID- 6249877 TI - Effect of acute metabolic acidosis on the renin-aldosterone system. Mechanism of increases in plasma aldosterone in dogs infused with lactic acid. AB - Recent observations suggest that PA increases during acute metabolic acidosis. The pathophysiological mechanism(s) involved remains undefined. In the present study, anesthetized mongrel dogs were infused with lactic acid (10 mEq/kg body weight) for 3 hr. During acidosis there was no change in plasma potassium concentration, a tendency for an incrase in PRA, and significant increases in PC (as a marker for ACTH secretion) and PA. Other dogs were infused with lactic acid after prior treatment with dexamethasone and propranolol or with dexamethasone alone. Under these conditions, the development of acidosis was not associated with changes in PC, plasma potassium, PRA, or PA, suggesting that the stimulatory effect of acidosis on PA is not a direct one but is mediated by concomitant increases in ACTH and/or PRA. PMID- 6249878 TI - Cartilage-associated collagenolytic activity in rabbits with antigen-induced chronic synovitis. AB - Rabbit articular cartilage fragments from knees with normal and antigen-induced chronic synovitis were assayed for active and latent collagenolytic activity. Significant levels of latent collagenolytic activity, as measured by hydroxyproline release, were associated with cartilage from chronic synovitis knee cartilage but not from normal knee cartilage. Neither normal nor chornic synovitis knee cartilage contained demonstrable levels of spontaneously active cartilage-associated collagenolytic activity. Cartilage-associated latent collagenolytic activity was demonstrated only after activation with either trypsin or p-aminophenylmercuric acetate and was inhibited by EDTA (10(-2)M) and 1,10-phenanthroline (10(-3) M). Cartilage-associated latent collagenolytic activity was demonstrated after incubation of activated cartilage at 37 degrees C but not 4 degrees C. The activity could not be removed or diminished by extensive prewashing of these cartilage fragments. Treatment of rabbits undergoing development of antigen-induced chronic synovitis, with methylprednisolone (1 mg/kg/day), significantly suppressed the level of cartilage-associated collagenolytic activity in antigen-challenged knees. The measurement of cartilage associated collagenolytic activity may be useful for the evaluation of potential antirheumatic drugs. PMID- 6249879 TI - Studies on osteoporosis III. Effect of estrogens and fluoride. AB - Total skeletal calcium levels were determined in female mice with the aid of whole body neutron activation analysis. Three months treatment with heparin produced significant osteoporosis in C3-H/St(Ha) mice but not in C57/BL6 (J) mice. Treatment with a conjugated natural estrogen preparation (Premarin) prevented heparin accelerated osteoporosis, but high level fluoride in the drinking water had no preventive effect. In some experiments there was a suggestion of a deleterious effect of fluoride. PMID- 6249880 TI - Studies on the possible role of cyclic AMP in limb morphogenesis and differentiation. AB - Recent studies indicate that one of the major functions of the apical ectodermal ridge (AER) of the embryonic chick limb bud is to maintain mesenchymal cells directly subjacent to it (i.e. cells extending 0.4-0.5 mm from the AER), in a labile, undifferentiated condition, and that when mesenchymal cells are freed from the AER's influence either artificially or as a result of normal polarized proximal to distal limb outgrowth, they are freed to commence cyto differentiation. In a preliminary attempt to investigate at a molecular level the mechanism by which the AER events its 'negative' effect on the cytodifferentiation of subjacent mesenchymal cells, we have examined the effect of a variety of agents that elevate cyclic AMP levels on the morphogenesis and differentiation of the unspecialized subridge mesoderm in an organ culture system. In vitro in the presence of the AER, undifferentiated subridge mesoderm explants undergo remarkably normal morphogenesis characterized primarily by progressive polarized proximal to distal outgrowth and changes in the contour of the developing explant. In the presence of cyclic AMP derivatives, explants fail to undergo the polarized outgrowth and contour changes characteristic of control explants. In fact, in the presence of dibutyrl-cyclic AMP and theophylline, AER directed morphogenesis essentially ceases during the first day of culture. The cessation of AER-directed morphogenesis in the presence of cyclic AMP derivatives is accompanied by the histochemically and biochemically detectable precocious chondrogenic differentiation of the subridge mesenchymal cells. In control explants, cartilage differentiation only occurs in those proximal cells of the explant which gradually become located greater than 0.4-0.5 mm from the AER. In contrast, in the presence of cyclic AMP derivatives, cartilage differentiation by cells within 0.4-0.5 mm of the AER is detectable from the first day of culture, and by the third day cartilage formation has occurred throughout the entire explant. Overall, these results indicate that elevating the cyclic AMP content of the subridge mesenchymal cells enables the cells to overcome negative influences on cytodifferentiation and the positive influences on morphogenesis being imposed upon them by the AER. On the basis of this observation and previous studies, a testable model on the role of cyclic AMP in limp morphogenesis and differentiation is proposed. PMID- 6249881 TI - Genetic mapping of xenotropic murine leukemia virus-inducing loci in five mouse strains. AB - A single mendelian gene was identified for induction of the endogenous xenotropic murine leukemia virus in five mouse strains (C57BL/10, C57L, C57BR, AKR, and BALB/c). This locus, designated Bxv-1, mapped to the same site on chromosome 1 in all strains: Id-1-Pep-3-[Bxv-1-Lp]. Thus, inducibility loci for xenotropic virus are more limited in number and chromosomal distribution than ecotropic inducibility loci. Virus expression in mice with Bxv-1 was induced by treatment of fibroblasts with 5-iododeoxyuridine or by exposure of spleen cells to a B cell mitogen, bacterial lipopolysaccharide. An analysis of the hamster X mouse somatic cell hybrids indicated that chromosome 1, alone, was sufficient for virus induction. PMID- 6249883 TI - Plasma membrane of Entamoeba histolytica. AB - Axenically propagated Entamoeba histolytica (HK9:NIH strain) were employed as starting material for the isoation of plasma membrane by a novel procedure. In the absence of known enzymatic markers, the externally disposed polypeptides of intact amoebae were iodinated and the incorporated label used to monitor membrane separation and recovery. 12 major plasma membrane polypeptides (12 x 10(3)-200 x 10(3) mol wt) were labeled and separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Each of these was a glycoprotein. Preincubation of amoebae with concanavalin A stabilized the plasma membranes as large sheets, facilitating its separation by low-speed centrifugation. Dissociation of the lectin with alpha methyl mannoside, followed by additional homogenization led to vesiculation and further purification. The isolated plasma membrane was recovered in high yield (28%) and enriched 30-fold in terms of incorporated iodide. All iodinated surface glycoproteins of the intact organism were present in the plasma membrane fraction. A Ca++-dependent ATPase was enriched in the plasma membrane to a similar extent, but over one-half of the total activity was associated with internal, unlabeled membranes, suggesting a dual localization of this activity. The isolated plasma membrane was enriched in cholesterol and had a cholesterol:molar ratio of 0.87. It also contained larger amounts of an unusual phospholipid--ceramide aminoethyl phosphonate--a phospholipase-resistant species. PMID- 6249882 TI - Cytopathogenic mechanisms of Entamoeba histolytica. AB - Cinemicrography of Entamoeba histolytica destruction of Chinese hamster ovary (CHO) cells shows that ameba cytopathogenicity consists of separate components: a contact-dependent cytolethal effect, and phagocytosis. Cells not in contact with amebae remain intact. Quantitation of ameba destruction of CHO cells by applying the one-hit hypothesis confirms that the cytoethal effect of amebae is contact dependent. Studies with 111Indium oxine-labeled cells provide further evidence of extracellular killing by E. histolytica and indicate that > 94% of the target cells are killed before phagocytosis. When we examined for a cytotoxin release by E. histolytica, we found no effect on CHO cells with filtrates of amebae, and a nonspecific effect of cell rounding and release with sonicates of amebae. The ameba sonicate effect was time-dose dependent, was not cytolethal, was reversible, and was inhibited by alpha II macroglobulin. Cytochalasin B altered ameba motility and morphology, and monolayer experiments confirmed that cytochalasins A, B, or D inhibited CHO cell destruction by E. histolytica. Cytochalasin D also inhibited extracellular killing of CHO cells by amebae in pellets, apparently independent of effects on ameba motility or phagocytosis. Colchicine and vinblastine, alone or in combination with cytochalasin D, did not inhibit E. histolytica cytopathogenicity, which indicates that microtubule function is not required for target cell killing by amebae. PMID- 6249884 TI - Stimulation of herpes simplex type I infection of C6 cells by trypsin-EDTA. AB - The nature of the refractoriness of C6 glioblastoma cells to herpes simplex virus type I (HSV-I) infection has been studied. The cells were restricted in susceptibility to HSV-I since only a small proportion of the cells could be infected by HSV-I and the virus yield per cell was low. The susceptibility to infection was increased by treating the cells with trypsin-EDTA prior to infection. The cells so treated recovered resistance to the virus when incubated at 37 degrees C, their resistance being restored to the initial level in 2 days. This restoration was inhibited by addition of cycloheximide or puromycin. Trypsin EDTA treatment of C6 cells increased the efficiency of adsorption of HSV-I and the formation of stable cell-virus complexes from which the virus could not be dissociated by heparin. PMID- 6249885 TI - Cell-mediated immunity in herpes simplex virus-infected mice: induction, characterization and antiviral effects of delayed type hypersensitivity. AB - Delayed type hypersensitivity (DTH) was induced ihe reaction was observed 4 to 5 days p.i. and could still be induced up to 18 months later. In contrast, the adoptive transfer of DTH using draining lymph node cells was only possible during the period 6 to 10 days p.i. The cells taken at these times also contained mediators of antiviral immunity, as determined by a marked reduction of virus titres in the ears of infected animals 1 to 3 days after transfer. Draining lymph node cells taken at later times contained mediators of virus immunity, but titres were not reduced until day 5 after the transfer. The cell type involved in both the DTH and antiviral activity was a T lymphocyte, although the particular T cell subsets involved have yet to be determined. PMID- 6249886 TI - Cell-mediated immunity in herpes simplex virus-infected mice: suppression of delayed hypersensitivity by an antigen-specific B lymphocyte. AB - Lymph node cells, regional to the site of infection with herpes simplex virus type 1 (HSV-1), when taken 1 to 9 months p.i. and transferred to HSV-1 immune recipients, suppressed the delayed type hypersensitivity (DTH) reaction to the virus. The suppressive activity was specific for HSV-1 and was transferred by a thy-1.2-negative, Ig-positive, lymphocyte population. Anti-HSV-1 serum did not suppress the HSV-1-induced DTH response. Contralateral lymph nodes contained little or no suppressor cell activity but in infected, adult thymectomized mice, these lymph node cells were as effective as the draining node in transferring suppression. The significance of these observations for the pathogenesis of herpes infections is discussed. PMID- 6249887 TI - The immune response against the ASV-coded src-gene product in syngeneic mice. AB - The antigenicity of the avian sarcoma virus (ASV)-coded src-gene product pp60src, which is responsible for fibroblast transformation after ASV infection, has been investigated in STU mouse fibrosarcoma cell lines and the corresponding immune response in syngeneic mice has been determined. The development of effective anti pp60src antibody titres depends on the mode and stie of injection of tumour cells and parallels tumour growth. It was found that mouse immunoglobulin heavy chains are unable to serve as substrate for the protein kinase activity of pp60src. Therefore, an indirect protein kinase absorption (PKA) test was initiated to demonstrate recognition of the protein kinase activity associated with the src gene product. The availability of syngeneic mice and the corresponding ASV transformed tumour cells should facilitate studies designed to elucidate the possible relationship between the cytoplasmic pp60src and ASV-induced tumour specific surface antigens (TSSA), for example, by allowing the production of stable mouse hybridomas synthesizing antibodies specific for pp60src and TSSA. PMID- 6249888 TI - Influence of trypsin on the infectivity and biological properties or parainfluenza type 2 type 2 (croup-associated) virus in Vero cells. AB - A comparative study on the infectivity and biological activities of parainfluenza virus type 2 revealed that one strain (Toshiba) showed c.p.e. with cell fusion and produced plaques in Vero cells, an established line of African green monkey kidney cells. Another strain (62-M786) of this virus, however, showed minimum c.p.e. and produced almost no plaques in Vero cells, although c.p.e. appeared and plaques were observed following addition of trypsin. The infectivity titre of the latter strain, estimated by 50% tissue culture infectious doses (TCID50), was increased 10 times and plaque counts more than 6400 times by addition of an adequate concentration of trypsin; however, trypsin did not affect the infectivity of the former strain. Trypsin also increased the haemolytic activity of strain 62-M786 but not that of the Toshiba strain. These results show that the two isolates of parainfluenza virus type 2 were affected very differently by trypsin as regards infectivity, cell fusion and haemolytic activity. PMID- 6249889 TI - Effect of acyclovir on recurrence of herpes simplex skin lesions in mice. AB - Acyclovir (ACV) was effective in preventing recurrence of herpes simplex in mice whose skin was stripped with cellophane tape. Treatment with ACV did not eliminate latent herpes simplex virus from the cervical ganglia. PMID- 6249890 TI - Cell fusion activity of bovine leukaemia virus. AB - Bovine leukaemia virus (BLV) induces two types of cell fusion. Cells inoculated at high multiplicity show cell fusion within 2 h. This type of fusion can be induced by non-infectious virus and does not require protein synthesis for induction. Low m.o.i. also induces cell fusion but this depends on production of infectious virus. PMID- 6249891 TI - Sensitivity of viruses to phosphorylated 9-(2-hydroxyethoxymethyl)guanine revealed in TK-transformed cells. AB - Vaccinia and pseudorabies viruses are resistant to ACV [Acyclovir or 9-(2 hydroxyethoxymethyl)guanine] in normal cells. However, both viruses are sensitive in thymidine kinase (TK)-transformed cells in which the resident HSV-specific TK is able to phosphorylate the drug. This demonstrates the sensitivity of these viruses to phosphorylated ACV and suggests a wider antiviral activity for the phosphorylated drug. PMID- 6249893 TI - Morphologic and immunopathologic findings in myasthenia gravis and in congenital myasthenic syndromes. AB - Overwhelming evidence now supports Simpson's concept, originally proposed in 1960, that acquired myasthenia gravis (MG) is an autoimmune disease in which antibodies are directed against the nicotine postsynaptic acetylcholine receptor (AChR).1 An autoimmune pathogenesis of acquired MG implies that those myasthenic syndromes which occur in a congenital and familial setting may have a different, non-autoimmune basis. This paper focuses on ultrastructural, immunoelectron microscopic and cytochemical aspects of acquired autoimmune MG and some recently recognised congenital myasthenic syndromes. PMID- 6249892 TI - Experimental autoimmune myasthenia gravis. AB - Injection of animals with purified acetylcholine receptor in complete Freund's adjuvant causes development of antibodies which crossreact with receptors in muscle. The crossreacting antibodies impair neuromuscular transmission. Animals with experimental autoimmune myasthenia gravis (EAMG) are excellent models for studying the complex mechanisms by which the autoimmune response to receptor in myasthenia gravis causes muscle weakness. This review first briefly describes the discovery of EAMG. Then, to provide the necessary perspective, receptor structure and function and properties of anti-receptor antibodies are discussed, followed by a brief review of the pathological mechanisms in EAMG. PMID- 6249895 TI - Clinical electrophysiology in myasthenia gravis. AB - Effective diagnostic methods are of great importance in order to recognise myasthenic patients among those with muscle fatigability. Intracellular recordings are useful for research work within the field and for detailed description of the motor end-plate's physiology in the individual case. The method is not used for the routine diagnosis of myasthenia gravis. The decrement of the electrical muscle response with nerve stimulation is the most commonly used method. The diagnostic yield is higher in proximal muscles, in warmed muscles, after exercise, and after ischaemia. A significant number of patients may be undiagnosed with this technique. The mechanical response with nerve stimulation shows the same type of decrement but also an abnormal response to long stimulation. The diagnostic value of this is under dispute. Single fibre ENG needs more patient cooperation than do these tests. The diagnostic yield is significantly higher. Some patients considered to have myasthenia gravis do not show any abnormalities with this technique, particularly those with the pure ocular form. Conventional EMG is not useful for the diagnosis of myasthenia, but may be indicated in these patients when concurrent nerve or muscle disease is in question. Tests for eye movement fatique have not proved useful. Stapedius reflex fatigability is demonstrated in about the same proportion of patients as have positive SFEMG findings. The technique is not uncomfortable for the patient and requires minimal cooperation. The general usefulness must be assessed by further routine use. Even with the advent of immunological tests, neurophysiological investigations are indispensable in helping establish the diagnosis of myasthenia gravis. Discrepancies between the results comparing electrophysiological and immunological tests may indicate that myasthenia gravis is a heterogenous entity within which subgroups may be identified. PMID- 6249894 TI - Mechanisms of acetylcholine receptor loss in myasthenia gravis. AB - The fundamental abnormality affecting the neuromuscular junctions of myasthenic patients is a reduction of available AChRs, due to an autoimmune attack directed against the receptors. Antibodies to AChR are present in most patients, and there is evidence that they have a predominant pathogenic role in the disease, aided by complement. The mechanism of antibody action involves acceleration of the rate of degradation of AChRs, attributable to cross-linking of the receptors. In addition, antibodies may block AChRs, and may participate in producing destructive changes, perhaps in conjunction with complement. The possibility that cell-mediated mechanisms may play a role in the autoimmune responses of some myasthenic patients remains to be explored. Although the target of the autoimmune attack in myasthenic patients is probably always the acetylcholine receptors, it is not yet clear which of these immune mechanisms are most important. It is likely that the relative role of each mechanism varies from patient to patient. One of the goals of future research will be to identify the relative importance of each of these mechanisms in the individual patient, and to tailor specific immunotherapeutic measures to the abnormalities found. PMID- 6249896 TI - Hepatoma visualization with Tc-99m pyridoxylidene glutamate. AB - Tc-99m sulfur colloid is concentrated in Kupffer cells of the liver, whereas the new biliary agents are processed by hepatic parenchymal cells. A case of primary hepatocellular carcinoma, appearing as a defect on sulfur-colloid liver scan and visualized on a biliary scan, is presented. The possible role of biliary scanning in the evaluation of a defect on sulfur-colloid liver scan is discussed. PMID- 6249897 TI - Pharmacokinetics of pertechnetate administered after pretreatment with 400 mg of potassium perchlorate: concise communication. AB - The pharmacokinetic behavior of pertechnetate in normal subjects has been studied. Each received 400 mg of potassium perchlorate 30 min before pertechnetate injection. Timed blood samples were collected and counted. The time activity curves for whole blood and plasma could both be fitted to an open two compartment model of the form 3 comes from 1 in equilibrium with 2, where Compartment 1 refers to the vascular pool, Compartment 2 to the perivascular pool, and Compartment 3 to the urine. The pharmacokinetic state equation is given by: leads to X = -KX. Rate constants determined were: k21 = 1.47 hr-1; k12 = 3.11 hr-1; k01 = 0.137 hr-1. The rate constants were the same for the whole-blood and plasma time-activity curves. PMID- 6249898 TI - Tc-99m glucoheptonate renal imaging: congenital mesoblastic nephroma. PMID- 6249899 TI - Intestinal microflora in the guinea pig as observed by scanning electron microscopy. Effect of fibrous dietary supplements. AB - The gastrointestinal ecosystems of weanling guinea pigs fed a purified diet with and without supplements of cabbage, alfalfa and holocellulose were examined by scanning electron microscopy. The diets, which were based on soybean protein, sucrose and wood cellulose, were fed for 28 days and the mucosa and associated microbes were fixed in situ. Bacteria, rods and cocci being the predominant morphological types, were commonly observed on the epithelial surface of the jejunum and ileum and much less frequently in the duodenum. In the cecum, fusiform- and spiral-shaped organisms were the most common types. The fusiforms, which produced unique indentations in the intestinal mucosa, were found in the intestines of the cabbage and alfalfa-supplemented guinea pigs but not in those fed the basal diet. There was considerably less mucus on the intestinal epithelium when the cabbage supplement was supplied. Whether promotion of the fusiform population or elimination of the mucus secretion are causally related to the growth stimulating properties of the supplements is not clear, but the results suggest a relationship. PMID- 6249900 TI - Mode of action of pharmacological doses of cholecalciferol during parturient hypocalcemia in dairy cows. PMID- 6249901 TI - Chemoprevention of tumor development and metastasis of transplantable hepatocellular carcinomas in rats by vitamin A. AB - Vitamin A is attracting increasing attention as a potential cancer chemopreventative agent. To investigate the effect of vitamin A on tumor establishment, growth and metastasis, rats were fed diets containing zero, adequate or excess (100X adequate) amounts of vitamin A prior to subcutaneous injection with transplantable hepatocellular carcinomas derived from solid tumors induced by N-2-fluorenylacetamide. When rats were injected at the same time the dietary regimen was begun, tumor growth was similar in both the deficient and adequate vitamin A groups with 20% less in the excess vitamin A group. However, when rats were injected 2 weeks post-initiation of the dietary regimen, tumors were fewer and appeared later under conditions of either vitamin A deficiency or excess. When rats were injected with a metastatic line 2 weeks following initiation of the dietary regimen, no metastases were observed in the animals fed excess vitamin A, but 60% had metastases in the deficient group and 75% in the adequate group. Results suggest that dietary extremes of vitamin A affect tumor establishment and growth and excess amounts prevent metastasis of transplantable hepatomas in the rat. PMID- 6249902 TI - Periodic ACTH discharge. AB - A 9 1/2-year-old girl is presented who had cyclical attacks of abdominal pain, vomiting, emotional disturbance, and marked weight change for two years. Associated findings were facial plethora, hypertension, transient hyperglycemia and glycosuria, elevated plasma ACTH, cortisol, and urinary 17-OHCS excretion, and low plasma osmolality with hyponatremia. Urinary excretion of catecholamines and porphyrin metabolites was not increased. Between episodes, she showed no abnormal clinical signs or laboratory data. The attacks were effectively suppressed with the administration of chlorpromazine. The disorder appears to be due to the periodic release of excessive ACTH; the cause remains unknown. PMID- 6249903 TI - Staphylococcal protein A adsorption of neonatal serum to facilitate early diagnosis of congenital infection. AB - The early diagnosis of congenital infection frequently depends on the ability to distinguish between infant IgM and maternal IgG antibodies. Staphylococcal protein A, which specifically binds IgG, removed maternal IgG from the serum of newborn infants. Residual IgM antibodies to CMV, rubella, toxoplasmosis, and syphilis were then identified by routine serologic techniques. Persistence of greater than or equal to 25% of the original antibody titer following SPA adsorption distinguished the sera of infants with congenital infection from those of healthy infants. No false negative results were encountered. Specificity of the serologic results of SPA-treated infant sera correlated with IgM-specific identification of the causative agent. Potentially false positive titers were identified by concurrent elevation of IgA or rheumatoid factor. Adsorption of cord or neonatal serum with SPA facilitates accurate serologic diagnosis of congenital infection. PMID- 6249904 TI - Adenovirus pneumonia. PMID- 6249905 TI - Collagenase in the human periodontal ligament. AB - Collagenase activity was demonstrated by direct incubation to be present in human periodontal ligament. This activity was found in only one of two populations of ligament, i.e., those ligaments taken from teeth in which their attachment site was at least 2.5 mm apical to the cementoenamel junction. The collagenase was demonstrated to be of host origin because it degraded collagen into 3/4 and 1/4 alpha chain fragments characteristic of mammalian collagenases. The enzyme was shown to be inhibited in the presence of EDTA and to have a pH optimum of 7.5. PMID- 6249906 TI - Rearrangement of chloramphenicol-3-monosuccinate. AB - The equilibrium mixture of chloramphenicol-3-monosuccinate and its alternate form at neutral pH in aqueous solution was reexamined. The structure of the alternate form was shown by mass specxtrometry and NMR spectroscopy to be chloramphenicol-1 monosuccinate and not the cyclic hemi-ortho ester reported previously. PMID- 6249907 TI - Differential effects of divalent cations, cation chelators and an ionophore (A23187) on morphine and dibutyryl guanosine 3': 5'-cyclic monophosphate antinociception. AB - The effects of intraventricularly (i.c.v.) administered divalent cations, cation chelators and an ionophore (A23187) on antinociception produced by i.c.v. administration of morphine or dibutyryl guanosine 3':5'-cyclic monophosphate (db c-GMP) were quantitated in the mouse tail-flick procedure. Ca++ pretreatment produced a dose-related potentiation (> 10-fold) of db c-GMP and a dose-related antagonism (> 20-fold) of morphine antinociception. Mg++ pretreatment antagonized db c-GMP, whereas morphine antinociception was unaffected. Ba++ and Sr++ were observed to possess intrinsic antinociceptive activity. Administration of Ba++ or Sr++ had greater than additive effects on db c-GMP and morphine antinociception. EDTA pretreatment did not affect db c-GMP or morphine antinociception. Ethylene glycol bis(beta-aminoethyl ether)N,N-tetraacetic acid had no effect on db c-GMP but potentiated the morphine response. The ionophore A23187 had no effect on db c GMP or morphine in the tail-flick test. However, A23187 potentiated the effect of high doses of Ca++ on db c-GMP and increased the antagonistic effect of a low dose of Ca++ on morphine antinociception. The results provide further evidence that the mechanism of db c-GMP antinociception is different from that of morphine. PMID- 6249908 TI - Binding of adenosine to the crude plasma membrane fraction isolated from dog coronary and carotid arteries. AB - In an attempt to elucidate the mechanism of action of adenosine, specific adenosine binding was determined by using plasma membrane rich microsomal fraction of dog coronary and carotid arteries. The binding of adenosine to both coronary and carotid preparations was temperature as well as pH dependent and was inhibited by aminophylline and adenosine nucleotides. Scatchard analysis of the saturable binding data on carotid arteries exhibited a single species of binding sites with a Kd value of 1.34 x 10(-6) M and binding capacity of 140 pmol/mg of protein. The first order dissociation rate constant of adenosine binding to carotid preparation was 0.0247 min-1. The nonlinearity of equilibrum binding data (Scatched Plot) and dissociation curve of binding to coronary arteries suggested the presence of more than one population of binding sites. The data suggest that the binding sites located in the microsomal fraction of coronary and carotid arteries possess the basic characteristics of the receptors which might be involved in the vasodilatory action of adenosine. PMID- 6249909 TI - Use of an uncoupling agent to distinguish between direct stimulation of metabolism and direct stimulation of transport: investigation of antidiuretic hormone and aldosterone. PMID- 6249910 TI - Specific, high affinity [3H]ethylketocyclazocine binding in rat central nervous system: lack of evidence for kappa receptors. AB - The binding properties and distribution of the tritiated benzomorphan, [3H]ethylketocyclazocine, were studied in rat central nervous system (CNS). Specific binding is saturable and represents 75 to 90% of total binding. Scatchard analysis is consistent with the existence of two classes of binding sites with Kd values of 0.5 and 10.5 nM, respectively. Ethylketocyclazocine binding is increased in the presence of sodium chloride. This characteristic resembles that of opiate antagonists rather than that of other agonists. The distribution of ligands. The IC50 values of various opioid agonists and antagonists for competition with [3H]ethylketocyclazocine correlate well with their IC50 values for competition with [3H]naloxone. This evidence does not lend support to the existence of a separate kappa receptor in rat CNS. PMID- 6249911 TI - Subcellular actions and potential adverse cardiac effects of the cardiotonic ionophore monensin. AB - Monensin concentrations between 0.5 and 30 microM produced dose-dependent positive inotropy when administered to normal, electrically driven rabbit left atria. These doses did not produce contracture. When monensin was combined with very low concentrations of ouabain (10 or 50 nM), irreversible contracture, irregular responses to electrical stimulation, or both, occurred in a significant number of atria treated with both drugs. This was apparently due to intracellular Na+ overload produced by both drugs, with secondary elevations of intracellular Ca++ concentrations. Monensin (17 nM, 1.7 or 170 microM) did not inhibit canine myocardial Na+mK+-adenosine triphosphatase activity. When administered to mitochondria isolated from normal rabbit hearts, monensin concentrations greater than 10 nM significantly depressed ADP-stimulated (State 3) respiratory rates and calculated respiratory control ratios. Maximum inhibition of the respiratory control ratio (85% decrease) occurred with monensin concentrations of 1 microM or more. These concentrations also significantly decreased calculated ADP:0 ratios. The data show that monensin concentrations required to increase contractility of isolated myocardium can produce marked inhibitory effects on isolated mitochondria, but apparently do not do so when the drug is administered to intact, normal cardiac tissue. PMID- 6249912 TI - Evidence for two distinct types of potassium-activated calcium channels in an intestinal smooth muscle. PMID- 6249913 TI - Effects of variations in extracellular acetylcholine and calcium ion concentration on the operational level of calcium channels in intestinal smooth muscle. PMID- 6249914 TI - Sustained cardiac beta adrenoceptor blockade in vitro and increased vulnerability to aconitine-induced arrhythmias in vivo after propranolol withdrawal in rats. AB - The present study was undertaken in order to investigate the possibility of cardiac hypersensitivity to norepinephrine (NE) after propranolol withdrawal in rats. The effect of NE was studied on heart rate and left intraventricular pressure development (maximal dP/dt) in the isolated perfused heart at various time periods after termination of the propranolol feeding. Also, the influence of propranolol withdrawal on vulnerability to aconitine-induced arrhythmias in vivo was evaluated in anesthetized rats. No hypersensitivity to NE was seen in the perfused rat heart 1 and 3 days after propranolol withdrawal. Rather, a depressed response to NE was registered suggesting a long half-life for the disappearance of beta adrenoceptor blockade. Increased vulnerability to aconitine-induced arrhythmias was observed 1 and 3 days after treatment with propranolol had ceased. Rats receiving propranolol continuously until experimentation exhibited an elevated threshold to aconitine-induced arrhythmias. These data indicate that a hypothetical rebound phenomenon after withdrawal of propranolol is not associated with an increase in mechanical performance of the heart in response to NE. A decreased threshold for development of arrhythmias appears, however, to be at hand, perhaps due to an inbalance in the transmembrane sodium flux in the heart in the early time course after propranolol withdrawal. PMID- 6249915 TI - [Adrenergic lipolysis in human fat cells: properties and physiological role of alpha-adrenergic receptors (author's transl)]. AB - Lipolytic activity of human isolated fat cells from different fat deposits was studied. The purpose of the present investigations was to determine the epinephrine responsiveness, with regard to alpha- and beta-adrenergic receptor site activity, of omental and subcutaneous adipocytes (abdominal or from the lateral part of the thigh). Adipocytes were obtained from normal subjects or from obese subjects on iso- or hypocaloric diets. The lipolytic effect of epinephrine varied according to the fat deposits, while the beta-lipolytic effect of isoproterenol was more stable (Fig. 1). We explored the possible involvement of adrenergic alpha-receptors, in order to explain these results. The potentiating action of phentolamine on epinephrine-induced lipolysis, and the antilipolytic effect of alpha-agonists on basal or theophylline--induced lipolysis, were found to be a good indication of alpha-adrenergic activity. The alpha-adrenergic antilipolytic effect was most prominent in adipose tissue from the lateral part of the thigh, and less noticeable in omental adipocytes. In conclusion, the inability of epinephrine to induce lipolysis, and the epinephrine-induced inhibition of lipolysis observed when the basal rate of FFA release was spontaneously increased in subcutaneous fat-cells of the thigh, could be explained by an increased alpha adrenergic responsiveness (Fig. 2). Moreover, various alpha-adrenergic agonists (phenylephrine, noradrenaline and adrenaline) showed a clear inhibiting effect on theophylline-stimulated adipocytes from the thigh. The pharmacological study of the antilipolytic effect of epinephrine on theophylline-induced lipolysis showed that the inhibition was linked to a specific stimulation of the alpha-receptors of the subcutaneous adipocytes (Fig. 4). From the different sets of experiments, it is shown that the modifications in the lipolytic effect of epinephrine on adipocytes of different areas could be explained by the occurrence of a variable alpha-adrenergic effect initiated by catecholamine. Furthermore, theophylline stimulation of lipolysis provides an accurate system to investigate the alpha-inhibiting effect of catecholamines. Our study was completed by the investigation of the lipolytic activity of subcutaneous fat cells from obese subjects submitted to a hypocaloric diet (800-1 000 Cal/day). An increased alpha-inhibitory effect of epinephrine was shown on the increased basal lipolytic activity observed in the fat cells of obese subjects on a hypocaloric diet (Fig. 5); a similar effect was observed when these adipocytes were stimulated by theophylline. To conclude, these investigations allow the alpha-adrenergic effect to be considered as a regulator mechanism of the in vitro lipolytic activity in human adipose tissue, since the antilipolytic effect is operative whenever the basal rate of lipolysis is increased (spontaneously, after caloric restriction, or with a lipolytic agent such as theophylline). PMID- 6249916 TI - Talking about sex--with less anxiety. PMID- 6249917 TI - Teaching and learning in a psychiatric-mental health clinical setting. PMID- 6249918 TI - Perception. PMID- 6249919 TI - Music: a milieu factor with implications for the nurse-therapist. AB - The effects of one type of music upon the social interactions observed in a group play therapy with ten male children, ages 8 to 10, were studied. A behavioral check list was developed to measure five target behaviors: the children's verbalizations, proximity with group members, proximity with the group co therapists, involvement in toy exchanges and involvement in acts of physical aggression. The resulting statistical analysis of tabulated data suggests music to be a factor in an increased number of social interactions. Consideration of such a milieu factor as music may prove valuable in many varying situations. PMID- 6249920 TI - A conceptual framework for psychiatric-mental health nursing. AB - A conceptual framework for a psychiatric-mental health nursing program gives direction for course content and becomes a rich source of hypotheses leading to development of theory. For this described framework tenets of humanistic theorists provide the philosophical base: Belief in the individual's responsibility, capacity and potential for growth; meaning of life; respect and dignity of the individual; and freedom of the individual for self-determination. Four major components comprise the framework: social systems and developmental theories, communication concepts, and self-esteem. Set in the nursing process schema, concepts from social systems and developmental theories are used in the assessment, concepts from communication theories are the basis for intervention, and changes in self-esteem become a measure of evaluation. The framework is applicable for individual clients, families, and/or groups. The nurse therapist is viewed in the same framework which may evolve into an intersystem model. Numerous research questions are suggested which may validate the relationships between the components of the framework. PMID- 6249921 TI - Attachment and short-term maintenance of motility and viability of Entamoeba histolytica in a defined medium. AB - Organic requirements for attachment to glass, elongation, and motility of Entamoeba histolytica, have been determined. The trophozoite, which has been grown axenically only in highly complex media with reduced oxygen tensions, remains rounded and detached when placed in a Tris-HCl buffered solution containing NaCl, KCl, MgClI, and CaCl2. A maintenance medium in which the amebae could attach to glass, elongate, and remain motile and viable for 12 to 24 h was devised with the addition of cysteine, ascorbic acid, bovine serum albumin, and the vitamin solution of medium NCTC No. 107. Tris-HCl was the most effective buffer tested and the optimal pH was 6.9 to 7.0. Survival, but attachment, of the amebae was decreased at osmolalities ranging between 110 and 180 milliosmoles/kg, whereas both functions were decreased above approximately 260 milliosmoles/kg. Bovine serum albumin, the most effective of the proteins tested, and the vitamin solution helped maintain attachment of some ameba strains, but were not required by other strains. The requirements for cysteine and ascorbic acid were absolute and highly specific. During incubation in the maintenance medium, cell volumes decreased. Sensitivity of the organisms to agglutination by concanavalin A, wheat germ agglutinin, soybean agglutinin and fucose binding protein remained unchanged. PMID- 6249922 TI - Structure of mitochondrial DNA from Paramecium tetraurelia. AB - Mitochondrial DNA (mtDNA) from endosymbiote-free stocks of Paramecium tetraurelia was isolated by 2 procedures. The buoyant density of the mtDNA in neutral CsCl was 1.702 gm/cm3, a value consistent with the melting temperature of the mtDNA. Only linear molecules were observed by electron microscopy. These molecules were homogeneous in size with a monomer molecular weight of 25.6 x 10(6) daltons. The size of the mtDNA determined after digestion with the restriction endonucleases EcoRI or Hind III agreed with the value obtained by electron microscopy. These studies also revealed that the digestion pattern of mtDNA from stock 172 differed from that of other 3 stocks (51, 127, 203) examined. Some mtDNA molecules exhibited snapback reassociation following denaturation. PMID- 6249923 TI - Giant fibroadenoma of the breast in young women. PMID- 6249924 TI - A non-functioning para-aortic paraganglioma. PMID- 6249925 TI - [Radiological appearances of congenital malformations of the hand (author's transl)]. AB - Pre- and post-operative radiological appearances of various isolated congenital malformations of the hand are described, as observed in a personal series of 52 cases. Six groups of malformations can be distinguished, and are, in decreasing order of frequency: agenesias, syndactylies, duplications, amniotic bands, arthrogryposis, and macrodactyly. PMID- 6249926 TI - Annual circulating testosterone levels in captive and free-ranging male armadillos (Dasypus novemcincuts). AB - Mean circulating concentrations and seasonal changes in plasma testosterone over 3 years were similar in free-ranging and captive male armadillos. The highest concentrations were seen in the summer months, i.e. at the time of maximum breeding, but the relatiely high values at other times and the inability of ACTH to restore dexamethasone-suppressed testosterone concentrations confirms that testicular function continues throughout the year. There was a gradual rise in plasma testosterone to adult levels from the 5th to the 9th month of life in captive-born males, indicating that sexual maturity is reached within the first year of life and that captivity is not deleterious to Leydig cell function. PMID- 6249927 TI - Psychological and social impact of gestational trophoblastic neoplasia. PMID- 6249928 TI - Neuropsychiatric lupus. AB - Sixty-six systemic lupus erythematosus (SLE) patients followed prospectively had 77 episodes of neuropsychiatric lupus (NPL). Patients with NPL had more SLE manifestations than patients without NPL. Serologic data and cerebrospinal fluid analysis were not helpful in identifying an episode of NPL. Electroencephalogram was abnormal in more than 1/2 and brain scans in more than 3/4 of patients. In 74 episodes with a known outcome, 54 improved, 44 having been treated with increased corticosteroids. Patients with NPL had a higher incidence of deaths compared to patients without NPL. PMID- 6249929 TI - Variation in plasma and urinary inorganic phosphate and pyrophosphate in normal subjects and in patients with acromegaly or osteoarthritis. AB - Plasma inorganic pyrophosphate (PPi) and inorganic orthophosphate (Pi) levels, urinary PPi and Pi excretion were measured every 2 h for a day in 4 normal subjects on a normal diet and again while fasting; 5 patients with osteoarthritis and 4 patients with acromegaly were also studied. Plasma Pi values were elevated at night in all subjects and were highest in the acromegalic patients. Mean plasma PPi was lower during fasting and correlated with Pi levels in all non fasting subjects. Urinary Pi and PPi were strongly correlated; both were lower in fasting subjects. Food intake and the time of blood sampling are important biological variables that must be considered when interpreting plasma PPi levels. PMID- 6249930 TI - Synthesis and analgesic activity of some 5-(4-hydroxyphenyl)-2 azabicyclo[3.2.1]octanes. AB - A representative series of 5-(4-hydroxyphenyl)-2-azabicyclo[3.2.1]octanes was synthesized and evaluated in vitro, as well as in vivo, as potential analgetic agents. In general, moderate to good activity (19 twice as active as morphine) was observed in the phenylquinone writhing assay (PQW), while only marginal activity was detected by the tail-flick method. Compounds 19 and 18, being the most active in the PQW model, also demonstrated weak binding affinity for the opiate receptors labeled by [3H]naloxone in rat brain homogenates. PMID- 6249931 TI - Derivatives of 5-hydroxy-6-methyl-2-aminotetralin. AB - The title compounds were designed to provide semirigid congeners of m-tyramine in which the ring position ortho to the phenolic OH is blocked to metabolic hydroxylation. A sequence leading to a key synthetic intermediate, 5-methoxy-6 methyl-2-tetralone, has been developed. In animal test models for dopamine-like effects, the title compounds demonstrated qualitative and quantitative differences from the isomeric 5-methyl-6-hydroxy-2-aminotetralins and from 5,6 dihydroxy-2-aminotetralins. Two of the compounds were potent in a cat cardioaccelerator nerve assay, which involves dopamine receptors. PMID- 6249932 TI - Simple beta-lactam compounds derived from 6-aminopenicillanic acid. AB - As part of a general program of structural modification in beta-lactam antibiotics, we have synthesized several simple penicillins from 6 aminopenicillanic acid where the C-3 carboxyl group has been replaced by a hydroxy or an acetoxy group and the C-6 side chain has been substituted by bromine or hydrogen. Some of the compounds exhibit mild activity against the Gram positive strain Bacillus subtilis. PMID- 6249933 TI - Conformationally restricted tricyclic antidepressants. 1. Octahydrodibenzazepinonaphthyridines as rigid imipramine analogues. PMID- 6249934 TI - Haemoglobin K Woolwich: a study of the family of a homozygote. AB - A family is described in which the proband is homozygous and several relatives are heterozygous for Hb K Woolwich (beta 130 [H10] Lys leads to Gln). These people are clinically and haematologically normal. The relationship between the presence of Hb K Woolwich and beta +-thalassaemia is discussed. The distribution of Hb K Woolwich in West Africa is discussed and it is seen to be closely associated with the Akan group. PMID- 6249937 TI - Partition coefficients of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO0 in erythrocyte lipids in multiple sclerosis. AB - Electron spin resonance (ESR) was used in a search for a possible generalized membrane defect underlying myelin instability in multiple sclerosis (MS). In contrast to most ESR studies of biological membranes, a small, nonelectrolyte spin label, TEMPO, was chosen; its partition coefficient was determined in extracted erythrocyte lipids from MS patients and normal controls. No differences were observed the advantages and limitations of TEMPO in comparison with lipid spin labels as probes for the study of biological membranes are discussed. PMID- 6249936 TI - Synthesis of peptides from amino acids and ATP with lysine-rich proteinoid. AB - Lysine-rich proteinoids in aqueous solution catalyze the formation of peptides from free amino acids and ATP. This catalytic activity is not found in acidic proteinoids, even though the latter contain some basic amino acid. The pH optimum for the synthesis is about 11, but is appreciable below 8 and above 13. Temperature data indicate an optimum at 20 degrees C or above, with little increase in rate to 60 degrees C. Pyrophosphate can be used instead of ATP, with lesser yields resulting. The ATP-aided syntheses of peptides in aqueous solution occur with several types of proteinous amino acid. PMID- 6249935 TI - Energy-transducing proteins in thermophilic biomembranes. AB - Biomembranes are the major site of energy transduction. The chemisomotic theroy of energy transduction is based on the following four major systems (i) H+-ATPase which is composed of a catalytic portion (F1) and a H+-channel (Fo), (ii) electron transport components, (iii) H+-linked porters, and (iv) a H+-impermeable lipid bilayer which is plugged through by systems i to iii that are specially oriented to translocate H+. Studies on the molecular mechanism of energy transduction have been hampered by the impurity, instability and complexity of preparations of membrane proteins from mesophilic organism. However, using stable, simple membrane proteins from a thermophilic bacterium, we obtained the following results: 1) Thermophilic H+-ATPase was dissociated into 5 subunits of F1 and 3 subunits of Fo and their functions and structures were studied by reconstitution. F1 was crystallized. 2) Thermophilic cytochrome oxidase, cytochrome c and NADH-dehydrogenase were purified. In contrast to the complex mitochondrial cytochrome oxidase (7 subunits) and NADH-dehydrogenase (3 subunits), the purified thermophilic proteins were shown to be composed of single components. 3) H+-linked porters such as a H+-driven amino acid carrier and a Na+ H+ antiporter were characterized. 4) Thermophilic lipids were shown to be completely saturated. Using these stable lipids, liposomes capable of H+-driven vectorial reactions including net ATP synthesis and alanine transport were reconstituted. PMID- 6249938 TI - Comparison of haemagglutination inhibition (HI) and indirect fluorescent antibody (IFA) techniques for the serological diagnosis of certain flavivirus infections. AB - Paired serum samples from 25 patients having clinical evidence of arboviral infections and 15 controls were examined for antibodies against dengue, Japanese encephalitis and West nile viruses by haemagglutination inhibition (HI) and indirect fluorescent antibody (IFA) methods. The two tests were comparable in specificity but the IFA test was found to be more sensitive than the HI test. Like the HI test, the antibodies detected by IFA test cross-reacted within the flavivirus group under test. Use of IFA test is recommended to detect flavivirus infections as the test is simple, sensitive and can be carried out rapidly. PMID- 6249939 TI - Neoplasms associated with hemihypertophy, Beckwith-Wiedemann syndrome and aniridia. AB - Hemihypertophy and the Beckwith-Wiedemann syndrome are associated with Wilms tumor and adrenocortical carcinoma. These conditions also have a relationship with nodular renal blastema, nephroblastomatosis and adrenocortical adenomas, all of which are pre-malignant lesions. children with aniridia also are predisposed to development of Wilms tumors. PMID- 6249940 TI - The Na,K-ATPase and its function in the regulation of intracellular ion and H2O concentration. Abstract. PMID- 6249941 TI - Cytochemical investigation on acid phosphatase activity in cerebral arteries in spontaneously hypertensive rats. AB - Acid phosphatase activity in the cerebral arterial system in spontaneously hypertensive rats (SHR) was cytochemically investigated. In the endothelial and medial smooth muscle cells, endoplasmic reticulums and Golgi complex revealed an intense acid phosphatase activity and primary lysosomes containing the high enzyme activity were found to be augmented in number. The enzyme activity was demonstrated in the vacuolated secondary lysosomes and in the intercellular spaces of the arterial walls. Lytic changes of the arterial mural cells and vessel matrix due to lysosomal enzymes were also evident. Causes of the lysosomal enzyme induction and roles of the enzyme in the developmental mechanism of hypertensive cerebrovascular changes in the SHR brain are discussed. PMID- 6249942 TI - Ionic current and pacemaker activity of the S-A node cells. AB - 1) Five membrane current (if, is, ik, ih, il) were observed in rabbit S-A node cells by the voltage clamp method. 2) The outward current (ik) was carried by k ion, while the inward current (is) was mainly carried by Na ion with some contribution of Ca ion. The inward current activated by hyperpolarization (ih) ws a mixed current system, but participation of Na and Cl ions was found to be existed. 3) Each current was analysed according to the Hodgkin-Huxley type equation. 4) Finally the action potential and pacemaker activity of S-A node were reconstructed. 5) In phase 4 diastolic depolarization, is played the major role, but the assistance of ik ws also important. PMID- 6249943 TI - [Sensitivity to FL 1060 (mecilliman) of E. coli and Klebsiella pneumoniae isolated from bile (author's transl)]. PMID- 6249944 TI - Changes of cyclic AMP concentration to isoproterenol after abrupt cessation of propranolol in rats. AB - Because the mechanism of adverse reactions to abrupt cessation of propranolol in patients with coronary heart disease was an enigma, we studied the effect of cessation of propranolol on beta-adrenergic receptor reactivity to catecholamine stimulation. The cyclic AMP concentrations in plasma and left ventricular muscle after the administration of isoproterenol (5 mg/Kg) were measured in rats before, during, 2 days after, and 4 days after of the administration of propranolol (5 mg/Kg). Two days after withdrawal from propranolol, the cyclic AMP concentrations in plasma and left ventricular muscle were significantly increased (p less than 0.005, p less than 0.01). Four days after withdrawal from propranolol, the cyclic AMP concentration in plasma was significantly increased (p less than 0.001). On the other hand, that of left ventricular muscle showed a tendency to have higher value, although, this was statistically not significant. From these results, this study suports that there is a hypersensitivity to adrenergic stimultion after abrupt cessation of long-term propranolol treatment. The explanation of propranolol withdrawal phenomenon most likely lies in lthe nature of beta adrenergic receptors that become activated during long-term blockade. PMID- 6249945 TI - [Response of plasma cyclic AMP to exogenous glucagon in patients with severe hepatic damage (author's transl]. PMID- 6249946 TI - [Clinical evaluation of angiographic portal vein findings and operability in hepatocellular carcinoma (author's transl)]. PMID- 6249947 TI - Hypotensive effect of captopril, an angiotensin converting enzyme inhibitor in pentobarbital anesthetized dogs. PMID- 6249948 TI - Effects of phthalazinol (EG 626) and pyridinolcarbamate (Anginin) on lipolytic enzyme activities in rat adipose tissue -in vivo and in vitro-. AB - Effects of Phthalazinol (EG 626), a cyclic AMP phosphodiesterase inhibitor, a thromboxane A2 antagonist and an antiatherosclerotic agent was examined regarding lipolytic enzyme activities in rat epididymal adipose tissue. The effect of Pyridinolcarbamate (Anginin) was concomitantly examined. There was a significant decrease in serum triacylglycerol levels in rats given EG 626 (100-500 mg/kg), p.o. for 1-3 weeks. In adipose tissue from EG 626 treated rats, the basal and adrenalin induced lipolysis, and cholesterylester hydrolase activity were markedly enhanced, while the phosphodiesterase activity was decreased. Anginin treatment had no effect either on the serum lipid levels or the cholesterylester hydrolase activity. An elevation in cholesterylester hydrolase activity and lipolysis by EG 626 was observed both in vivo and in vitro. Incubation of the adipose tissue with 0.229 mM of EG 626 or 0.603 mM of theophylline induced a lipolysis equivalent to that seen with 2.7 x 10(-2) mM of adrenalin. These results indicate that EG 626 exerted marked effects on lipolysis and cholesterylester hydrolase activity, probably through inhibition of phosphodiesterase. Possible contributions of the enhanced cholesterylester hydrolase activities to the antiatherogenic effect were discussed. PMID- 6249949 TI - Immunologic cytotoxicity against autologous human lymphocytes transformed or infected by Epstein-Bar virus: role of antibody-dependent cellular cytotoxicity in health individuals. AB - Immunologic cytotoxicity against lymphocytes transformed or infected by Epstein Barr virus (EBV) was mainly studied in an autologous in vitro system by 51Cr release assay and EBV-determined nuclear antigen (EBNA)-specific trypan blue exclusion method. When the cells of newly established EBV-transformed or spontaneously transformed lines were incubated with unfractionated autologous healthy donor lymphocytes or T-cell-depleted lymphocytes in the presence of EBV positive autologous or allogeneic serum, the transformed cells were killed with high frequency. Exposure to lymphocytes alone or to EBV-positive serum alone was not effective. The cytotoxic reaction was directed against cells positive for EBV induced membrane antigens (MA) but not against MA-negative transformed cells. A very small fraction (1 of 200) of healthy donor lymp]hocytes exposed to EBV converted into EBNA-positive and MA-positive cells, and these were also killed by the remaining autologous lymphocytes in the presence of EBV-positive serum. These results indicated that the present cytotoxic reaction represents antibody dependent cellular cytotoxicity (ADCC), and this particular mechanism probably plays an important role in the immunologic surveillance in the protection against EBV-induced oncogenesis in seropositive individuals. Such ADCC, however, does not seem to function effectively in patients with systemic lupus erythematosus. PMID- 6249950 TI - Effect of dithiothreitol on plasma membrane intramembranous particle topography in BALB/c 3T3 and simian virus-transformed 3T3 cells and plasma membrane vesicles. AB - A statistical analysis of plasma membrane intramembranous particle topography was performed on purified 3T3 and simian virus (SV)-transformed 3T3 plasma membrane vesicles and on intact 3T3 and SV3T3 cells. The results show that intramembranous particles were more aggregated in intact 3T3 cells than in intact SV3T3 cells. By contrast, in purified plasma membrane vesicles intramembranous particles were significantly more aggregated in SV3T3 than in 3T3 preparations. These unexpected results suggest that intramembranous particle topography is selectively altered in SV3T3 plasma membranes during the membrane vesicle isolation procedure. Inasmuch as the disulfide-reducing agent dithothreitol (DTT) was used to isolate membranes, tests were done to determine if DTT would preferentially affect particle topography in intact SV3T3 cells. Exposure of intact SV3T3 cells to 10 or 50 mM DTT induced intramembranous particle aggregation but had no effect on intact 3T3 cells. Preliminary studies also showed that other sulfhydrylreactive compounds preferentially induced particle aggregation in SV3T3 specimens. These observations suggest that the state of cross-linking of membrane-associated proteins by disulfide bonding influences intramembranous particle topography and that differences exist in plasma membrane-associated sulfhydryl proteins in nontransformed and transformed cells. PMID- 6249951 TI - Properties of mouse embryo fibroblasts transformed in vitro by infectious bovine rhinotracheitis virus. AB - Infection of CD-1 mouse embryo fibroblast(s) (MEF) with infectious bovine rhinotracheitis virus (IBRV) strain HMC resulted in persistent infection and subsequent transformation of these cells. IBRV-transformed MEF cultures consisted of short fibroblastoid cells, and IBRV-specific membrane and intracellular antigens were detectable in early in vitro passages by indirect imunofluorescence (IF) techniques. The presence of IBRV genetic information was confirmed in IF positive and IF-negative cells by in situ hybridization. IBRV-transformed MEF induced fibrosarcomas in athymic nude mice given sc transplants. Infectious virus could not be rescued from the transformed cells or from tumor cells by cocultivation with rabbit kidney cells, by treatment with 5-iodo-2'-deoxyuridine, or by UV irradiation. Nontransformed control cells did not survive more than 10 in vitro passages and did not induce tumors when transplanted to athymic nude mice. These observations represent new data concerning the mouse cell transforming potential of IBRV and confirm the presence of at least part of the virus genome in the transformants. PMID- 6249952 TI - Non-T-cell-mediated cytotoxicity in mice with tumors induced by Moloney murine sarcoma virus (M-MuSV). II. Granulocyte-mediatd cytotoxicity against autochthonous target cells isolated from M-MuSV-induced tumors. AB - Experiments were performed in A/Sn and A/WySn mice to determine the specificity, organ distribution, and further characteristics of the small non-T-cells that infiltrate Moloney murine sarcoma virus (M-MuSV)-induced tumors and are capable of killing the autochthonous M-MuSV-infected tumor target cells. Continuous bovine serum albumin density gradient separation proved to be the most effective method of enriching the cytotoxic cells. Increase in cytotoxic activity, measured by both the 51Cr release assay and the microcytotoxicity test, paralleled the increase in the proportion of polymorphonuclear leukocytes in mice bearing M-MuSV induced tumors also contained myeloperoxidas-positive cytotoxic effector cells. The cytotoxic activity appeared to be nonspecific. Various mouse tumor lines as well as allogeneic fibroblasts were sensitive to these effector cells. The only target cell type not affected was the syngeneic fibroblast. In addition to the tumor mass, cytotoxic cells were found in the bone marrow, blood, and spleens of mice bearing M-MuSV-induced tumors. Only bone marrow cells from normal mice exhibited cytotoxic activity. Thus cells of the myelopoietic series may be important in fighting M-MuSV-induced tumors by way of their direct cytotoxic effects on the infected cells. PMID- 6249953 TI - [Effect of cytochrome C of plant origin on experimental cardiac arrhythmia and myocardial contractile function and energy metabolism]. PMID- 6249954 TI - [Characteristics of 3H-dihydroalprenolol binding to beta-receptors in the fat cells of rats and spontaneous genetic hypertension and in hypertensive disease]. AB - The binding of 3H-dihydroalprenolol, a beta-antagonist, with the fat cell plasma membrane was studied in spontaneously hypertensive rats and in patients with essential hypertension. It was found that, as compared to control rats, hypertensive animals had an increased maximum number of 3H-DHA binding sites in the membranes and diminished affinity of beta-adrenoreceptors. It is suggested that these differences may play an essential role in the latered sensitivity to adrenalin in hypertensive rats. Removal of the adrenal, i. e. deprivation of the stabilizing corticosteroid effect, leads to marked changes in the state of the beta-adrenoreceptors in hypertensive animals. Thus, the maximum number of binding sites reduces in hypertensive rats but remains unaltered in the controls; following adrenalectomy the affinity of beta-adrenoreceptors increases in rats with hypertension, but in normal rats, on the contrary, does not change or rather has a tendency to decrease. PMID- 6249955 TI - Cholinergic inhibition of urinary acidification by the turtle bladder. AB - The effect of carbachol on urinary acidification by the turtle bladder in vitro was studied. Carbachol inhibited urinary acidification in a dose-dependent fashion, with half maximal inhibition occurring at 4.5 x 10(-5) M. The effect of carbachol on urinary acidification could be totally prevented by atropine, indicating that the inhibition is mediated through a muscarinic receptor. Carbachol inhibited hydrogen ion secretion by decreasing the active proton conductance and not by altering the proton motive force. Carbachol failed to increase passive loss of hydrogen ion from the mucosa. Carbachol increased calcium uptake by the turtle bladder; this increase in calcium uptake could be prevented by pretreatment with atropine, pentobarbital, or lanthanum. Pentobarbital or lanthanum blunted the inhibitory effect of carbachol on hydrogen ion secretion. In the presence of low extracellular calcium (0.2 mM), carbachol failed to increase calcium uptake but caused a significant inhibition of hydrogen ion secretion. In the presence of normal calcium concentration, carbachol caused a significant efflux of calcium. These data demonstrate that carbachol inhibits urinary acidification and suggest that the mechanism of this inhibition may be related, at least in part, to changes in cytosolic calcium. PMID- 6249956 TI - Comparative study of an angiotensin-II analog and a converting enzyme inhibitor. AB - The effects of an angiotensin-II analog (saralasin, i.v.) and of a converting enzyme inhibitor (captopril, oral) were compared in 12 sodium-depleted patients with hypertension. The decrease of the mean intraarterial pressure (MAP) with captopril (-21.5 +/- [SEM] 4.3 mm Hg) was more pronounced (P < 0.001) than the change of MAP during saralasin (-10.5 +/- 4.0 mm Hg). The pretreatment arterial plasma renin activity (log PRA) was closely related to the change of MAP during saralasin (r = -0.94; P < 0.001) and also to the captopril-induced change of MAP (r = -0.82; P < 0.001); similar results were obtained for the log plasma angiotensin (PA) I and II levels. The change of MAP was more pronounced, however, with captopril than during saralasin at any level of pretreatment PRA, PAI or PAII. Saralasin did not affect heart rate (P > 0.4), but during captopril the heart rate increased by 5.1 beats/min (P < 0.001). Captopril produced a 70% decrease of PAII, but the change of MAP was poorly related to the changes of PAII (r = -0.57; P < 0.05); PRA and PAI rose threefold to fourfold. PRA, PAI, and PAII all increased during saralasin. These observations may suggest that the antihypertensive action of captopril is not based solely on the inhibition of AII formation, but also the agonistic effect of saralasin has to be considered. PMID- 6249958 TI - [Drugs. Drug addicts. I]. PMID- 6249957 TI - [Influence of vitamin D therapy on renal osteodystrophy in children (author's transl)]. AB - Growth arrest and renal osteodystrophy is a major problem in renal insufficiency of children. The present report describes our experiences in managing renal osteodystrophy by using vitamin D3 for 24 months. Values in plasma of Ca, Mg, alkaline phosphatase, iPTH, 25-OH-D were determined regularly. Skeletal X-rays and analysis of iliac crest bone biopsies were obtained in each child. In treatment with vitamin D3 no hypercalcemia was seen despite high serum levels of 25-OH-D. Plasma-Ca, alkaline phosphatase, and iPTH normalized nearly. Radiographic abnormalities improved. Bone biopsies showed improvement in signs of secondary hyperparathyroidism and ostitis fibrosa, whereas osteomalacia remained unchanged. Osteoblast population showed a small reduction. No real increment in body growth was seen. PMID- 6249959 TI - [I used to like drugs]. PMID- 6249960 TI - [Society, creativity, drug addiction]. PMID- 6249962 TI - [You keep yourself aloof...]. PMID- 6249961 TI - [Youth, drugs and our responsibility]. PMID- 6249963 TI - [Courses for prevention in schools]. PMID- 6249964 TI - [Short considerations on education in drug matters in schools]. PMID- 6249965 TI - [Unimpeded liberation from the ghetto of drug addiction]. PMID- 6249966 TI - [Sleep: a hospital survey]. PMID- 6249967 TI - After a so-called "global" study of visiting hours at the district hospital in Geneva; some surprising conclusions. PMID- 6249968 TI - [Fits and starts with 3 former presidents of the Swiss Nurses' association: thank you to Erika Eichenberger and Marguerite Schor]. PMID- 6249969 TI - [Rooming-in. 2. Rooming-in and demand feeding for the newborn infant]. PMID- 6249970 TI - [Psychological aspects in geriatrics]. PMID- 6249971 TI - [Motivation for resigning: intermediate balance]. PMID- 6249972 TI - Basement membrane synthesis in spontaneously diabetic Mystromys albicaudatus. PMID- 6249973 TI - Acute cytomegalovirus glomerulonephritis: an experimental model. AB - HA/ICR mice injected intraperitoneally with an LD(10) of murine cytomegalovirus develop a transiet acute glomerulonephritis characterized by cytomegalic intranuclear inclusions limited to mesangial cells. Viruria and proteinuria occur on the 3rd day and usually subside by the 10th day, accompanied by resolution of the glomerular lesion. By electron microscopy, virus synthesized within mesangial cell nuclei accumulates in intercelluar channels that course through the mesangial matrix. Virus and cellular debris are also found in channels surrounded by matrix in the juxtaglomerular area and between the epithelial cells of the macula densa. By immunofluorescence, viral antigen first concentrated in glomerular mesangial cells on the 5th day is cleared centripetally, appearing as fine granules in the juxtaglomerular area by the 7th day after infection. By the 10th day, changes are restricted to the juxtaglomerular region, and thereafter hyalinization at the glomerular vascular pole or cellular disarray of the juxtaglomerular zone with lymphocytic infiltration extending into the renal interstitium from few glomeruli occurs in approximately 40 per cent of the mice associated with persistence of viral antigen in these foci. These findings indicate that at least one route of transport resulting in viruria involves the glomerular mesangium, juxtaglomerular zone, and the distal convoluted tubule. Persistence of viral antigen or other noxious substances along this route may result in a unique juxtaglomerular lesion and interstital nephritis. PMID- 6249974 TI - Unavailable carbohydrates of commonly consumed indian foods. PMID- 6249975 TI - The use of guinea pig K+-depolarized tracheal chain preparations in beta adrenoceptor studies. AB - Guinea pig tracheal chain preparations were K+-depolarized using Krebs solution in which all the Na+ was replaced by an equivalent amount of K+. This caused a sustained contraction of the preparations. Reproducible concentration-response (relaxation) curves to isoprenaline could be obtained provided that the preparations were repolarized by washing in normal Krebs solution between curves. pA2 values for propranolol (8.30) and butoxamine (5.89) were in good agreement with values obtained on other types of tracheal preparation. The maximum relaxation to salbutamol was less than that to isoprenaline and the maxima to both drugs were less than the maximum relaxation of the tissue (to papaverine). It is suggested that K+-depolarized tracheal preparations have no beta adrenoceptor reserve and may, therefore, be useful in studies designed to compare the efficacies of beta-adrenoceptor agonists. PMID- 6249976 TI - The effect of ascorbic acid on the interaction of adrenaline and neostigmine on neuromuscular transmission. AB - Ascorbic acid is used in the laboratory as a stabilizing agent to delay the oxidation of adrenaline solutions. The rat isolated phrenic nerve-diaphragm preparation was used to study the interaction of ascorbic acid, adrenaline and neostigmine on neuromuscular transmission. While ascorbic acid itself did not affect the response of the preparation to phrenic nerve stimulation, it significantly reduced the response of the preparation to neostigmine and the augmentation of this response by adrenaline. The results emphasize the need to consider the consequences of including preservatives or stabilizing agents in drug solutions when quantitative comparisons are made. PMID- 6249977 TI - [Double-label scintigraphy in the diagnosis of hepatocarcinoma]. PMID- 6249978 TI - [Primary liver carcinoma and markers of virus of type B hepatitis (author's transl)]. AB - Association of primary liver carcinoma with virus of type B hepatitis has been demonstrated around the world, especially in African and Asian countries where high titles for surface antigen of B hepatitis (HBsAg) have been found. Presence of viral markers of B hepatitis has been studied in a group of 34 patients with primary liver carcinoma, in 139 cirrhotic patients, and in 100 normal individuals. Positive titles of HBsAg or of antibodies against "core" antigen (anti-HBc) without evidence of antibodies against HBsAg (anti-HBs) were considered as positive markers for virus B infection. Percentages of positive markers in the series studied were as follows: 52% in the cases of primary liver carcinoma, 38% in the cirrhotic cases, and 5% in the control subjects. There is a significant difference in relation to the incidence of viral markers between patients with liver carcinoma and normal controls. A possible role of the virus of B hepatitis in the pathogenesis of primary liver carcinoma could be suggested on the basis of these results. PMID- 6249979 TI - [Hepatic tumors and environmental factors]. PMID- 6249980 TI - [Clinical aspects, diagnosis, treatment and etiology of pyrophosphate arthropathy]. PMID- 6249981 TI - [The value of aspiration cytology in giant breast tumors (author's transl)]. AB - Examinations by fine-needle biopsy are compared with histological data. In preoperative diagnosis aspiration cytology is a useful method which provides useful information on the nature of giant breast tumors. Giant tumors should be aspirated in several places. PMID- 6249982 TI - Malignant fibrous histiocytoma of the head and neck. AB - Eight cases, the largest series of malignant fibrous histiocytomas of the head and neck to date, are reported. In over one-half of the cases, the initial problems encountered in the case made the true diagnosis misleading. For correct diagnosis multiple biopsies may be required. The diagnosis is further confirmed by the clinical behavior of the tumor and its site, size, and depth of involvement. Four specific histopathologic variants are described. Wide surgical excision is the preferrred treatment. The potential role of adjunctive irradiation should be considered. PMID- 6249983 TI - Hormones in milk. PMID- 6249984 TI - The effect of acid-base changes on vasopressin-stimulated water flow in toad urinary bladder. PMID- 6249985 TI - Opioids modulate periodicity rather than efficacy of peristaltic waves in the guinea pig ileum in vitro. PMID- 6249986 TI - Ethanol and prostaglandin E1: biochemical and behavioral interactions. PMID- 6249987 TI - The effects of insulin on choline kinase activity in cultured rat liver cells. PMID- 6249988 TI - Cholecystokinin octapeptide: vesicular localization and calcium dependent release from rat brain in vitro. PMID- 6249989 TI - Regional sensitivity of cyclic AMP and cyclic GMP in rat brain to central cholinergic stimulation. PMID- 6249990 TI - Changes in the relationship between cerebrospinal fluid and blood composition produced by ACTH treatment in conscious sheep. PMID- 6249991 TI - FSH receptors in isolated Sertoli cells: changes in concentration of binding sites at the onset of sexual maturation. PMID- 6249992 TI - Chronic antidepressant treatment enhances alpha-adrenergic and serotonergic responses in the facial nucleus. PMID- 6249993 TI - Increased sensitivity of heart cell cultures to norepinephrine after exposure to polyamine synthesis inhibitors. PMID- 6249994 TI - The calcium requirement in GnRH-stimulated LH release is not mediated through a specific action on receptor binding. PMID- 6249995 TI - Correlation between circular dichroism data and biological activities of 2,5 substituted enkephalin analogues. PMID- 6249996 TI - In vitro cyclic AMP-mediated lipolytic activity of endorphins, enkephalins and naloxone. PMID- 6249997 TI - The direction of opiodid agonists towards mu-, delta- and epsilon-receptors in the vas deferens of the mouse and the rat. PMID- 6249998 TI - ATP-dependent calcium transport in cardiac sarcolemmal membrane vesicles. PMID- 6249999 TI - Pharmacology of excitatory amino acid receptors mediating the stimulation of rat cerebellar cyclic GMP levels in vitro. PMID- 6250000 TI - Dissociation between ACTH and beta endorphin immunoreactivity in cells of the rat pituitary gland. PMID- 6250001 TI - Ontogenesis of enkephalinergic systems in rat brain: post-natal changes in enkephalin levels, receptors and degrading enzyme activities. PMID- 6250002 TI - Effect of diet on choline phosphotransferase, phosphatidylethanolamine methyltransferase and phosphatidyldimethylethanolamine methyltransferase in liver microsomes. PMID- 6250003 TI - [Radionuclide diagnosis of acute myocardial infarct]. PMID- 6250004 TI - [Assessment of left ventricular contractile function by a radionuclide ventriculography method]. PMID- 6250005 TI - [Use of radioactive technetium-labelled erythrocytes for studies of the heart]. PMID- 6250006 TI - [Radiation changes in the regional lymph nodes and their effect on the migration of tumor cells]. PMID- 6250007 TI - [Induced radioactivity in the tissues under the action of high-energy protons]. PMID- 6250008 TI - The effects of fasting on glucagon binding and action in isolated rat hepatocytes. PMID- 6250009 TI - The fate of a large bolus of exogenous estrogen administered to postmenopausal women. AB - Seventeen postmenopausal women were given a bolus of conjugated estrogens (USP, Premarin), 17 beta-estradiol and estriol orally, intravenously or by pellet implantation, and circulating levels of estrone, estradiol and/or estriol were measured by radioimmunoassay at various intervals during a 48--72-h period. Oral administration resulted in a marked rise in serum estrone; parenteral administration resulted in a marked increased in serum estradiol. There was no significant fall in serum gonadotropins during this period. Following estriol administration orally, there was a decided elevation in estriol levels but minimal change in estrone and estradiol. PMID- 6250010 TI - Plasma levels of ACTH and cortisol in bilharzial and non-bilharzial individuals during halothane and nitrous oxide anaesthesia. AB - The effect of stress of anaesthesia and surgery was studied in non-bilharzial and bilharzial individuals. Estimation of ACTH and cortisol was carried out by the radio-immunoassay (RIA) technique. The level of ACTH and cortisol was found to be lower in unanaesthetized bilharzial subjects than in normal individuals. Under the effect of anaesthesia and surgery the elevation in the level of both hormones was also lower in bilharzial than in non-bilharzial patients. The response to the stress of anaesthesia and surgery was more marked during halothane than during nitrous oxide anaesthesia. PMID- 6250011 TI - [Relationship between polymyxin B and M biosynthesis and the amount and age of the inoculum]. PMID- 6250012 TI - [Isolation and partial purification of the intracellular phosphatases of Propionibacerium shermanii]. PMID- 6250013 TI - [Glucose transport and catabolite repression in Endomycopsis fibuligera yeasts]. AB - The role of systems for glucose transport in the manifestation of carbon catabolite repression of glucoamylase synthesis was studied in the yeast Endomycopsis fibuligera. Experimentas were conducted with its mutant AB-192 defective in the system of transport universal for glucose and 2-deoxy-D-glucose (2-DG). The nature of the mutation was established from the following data: (1) transport of labeled glucose into the mutant cells was twice as low in comparison with the parent culture 20-9; (2) transport of labeled 2-DG was suppressed almost entirely; (3) no competition was found between glucose and 2-DG for penetration into the mutant cells. Glucoamylase synthesis in the mutant AB-192 was not sensitive to catabolite repression by glucose. This was confirmed by the resistance of the AB-192 cells to the inhibition by glucose and their complete resistance to the repression by 2-DG. Moreover, an addition of cAMP did not stimulate glucoamylase synthesis by the mutant culture in the presence of glucose and 2-DG. It can be concluded therefore that the resistance of the yeast to catabolite repression by the glucose is caused by the mutation in the system for carbohydrate transport. The results suggest that the system of glucose transport plays an important role in the manifestation of carbon catabolite repression in the yeast Endomycopsis fibuligera. PMID- 6250014 TI - [Immobilization of methane-oxidizing bacterial cells]. AB - The purpose of this work was to study how the conditions for immobilizing the cells of the methane oxidizing bacterium Methylomonas rubra using chemical and physical techniques influence their functional catalytical properties. These properties were found to depend on the chemical nature of a matrix and the mode of binding the cells to the carrier. The best carriers were shown to be silochrome with introduced carboxy groups and agar gel. PMID- 6250015 TI - What controls collagen resorption in vivo? AB - The local control of collagen degradation in mammals in vivo is currently considered to depend primarily on variations on the level of activity of specific collagenases. Such variations are believed to depend on three factors: a) the rate of active collagenase synthesis and/or of activation of inactive enzyme precursors; b) the action of serum and/or tissue collagenase inhibitors; and c) different combinations of both mechanisms. We suggest that another element contributing to the regulation of collagen degradation in vivo is the susceptibility of the substrate. Support for this suggestion is derived from two sources: 1) experimental data, indicating that the rate of collagen degradation depends on the genetic type of substrate, on its state of aggregation (including degree of cross-linking), and on the nature and amount of other macromolecules associated with collagen in vivo. Other experimental findings supporting our hypothesis are the universal presence of collagen-bound collagenase, the apparent greater affinity of the enzyme for the more recently synthetized substrate molecules, and the increased amounts of intact collagen that may be solubilized from some tissues undergoing massive collagen degradation, 2) analogy with currently accepted views on intracellular protein catabolism, which cannot be rejected a priori as irrelevant to the problem. PMID- 6250016 TI - Ion migration through cell membranes: is it a process of diffusing corpuscles or diffracted ion matterwaves? AB - Justifications are presented for treating the process of ion migration through cell membranes not as a process of diffusing corpuscles but as a process of ion matterwaves being diffracted or reflected at the membrane corresponding to a permeable or an impermeable membrane. A qualitative explanation of the actions of anesthetics is given using the wave mechanical concept. PMID- 6250017 TI - Detection of enterovirus specific IgG and IgM antibodies in humans by an indirect solid phase radioimmunoassay. AB - The development of a solid phase radioimmunoassay which is able to detect virus specific IgG and IgM antibodies in serum specimens from patients with enterovirus infections is described. Viral antigen partially purified from infected tissue culture fluid was absorbed passively to individual polystyrene microtiter wells. Dilutions of sera were incubated on these antigens and bound anti-viral antibodies were monitored by the addition of 125-iodine labeled anti-human-IgG or anti-human-IgM antibody. Specificity of the assay to detect virus-specific IgM antibody was ensured by highly specific anti-IgM antibody which did not cross react with IgG and 2-mercaptoethanol sensitivity of IgM antibody titers. Changes of IgM antibody titers clearly indicated a current infection by that virus strain which was isoalted as etiological agent. Advantages and restrictions of the introduced radioimmunoassay are discussed. PMID- 6250018 TI - Combined antiviral effect of DNA inhibitors on Herpes simplex virus multiplication. AB - The inhibition of herpesvirus type 1 in cell cultures by seven inhibitors of DNA synthesis and by pactamycin was investigated by plaque inhibition in Vero cells with agarose overlay, and by yield reduction in one-step growth in HeLa cells. While the plaque inhibition method proved to be suitable to show inhibition by single substances, only the yield reduction procedure was reliable for investigating the interaction of two substances. Inhibition was evaluated by means of an inhibition quotient (number of PFU in uninhibited virus controls:number of PFU in test specimen); combined inhibition was related to results with single substances. Among the 28 substance pairs, 9 cases of indifference, 10 additive, and 9 synergistic interactions were found. Indifference was observed only with fluorodeoxyuridine and amethopterin as one of the partners, which by themselves inhibited herpesvirus multiplication incompletely. PMID- 6250019 TI - Mechanisms of thyroid hormone action. PMID- 6250020 TI - Phosphorylation of rabbit skeletal muscle glycogen synthase I by the cAMP dependent protein kinase, the cAMP independent synthase kinase and the phosvitin kinase from human polymorphonuclear leukocytes. PMID- 6250021 TI - Hydrophobic interaction of soluble 3':5' cyclic nucleotide phosphodiesterase with octyl-sepharose. PMID- 6250022 TI - The enzymes involved in the synthesis of phytic acid in Lemna gibba (studies on the biosynthesis of cyclitols, XL.(1)). AB - The biosynthesis of phytic acid is known to be catalyzed by enzymes causing a stepwise phosphorylation of myo-inositol or 1L-myo-inositol 1-phosphate with adenosine triphosphate as phosphate donor. The kinase responsible for these phosphorylations in Lemna gibba were purified by affinity chromatography on a Sepharose gel carrying myo-inositol 2-phosphate at the binding site. Three fractions with enzymatic activity could be identified; in the first one, we find myo-inositol kinase (EC 2.7.1.64) phosphorylating myo-inositol to 1L-myo-inositol 1-phosphate; the second one brings about the phosphorylation of myo-inositol trisphosphate to phytic acid; the third one phosphorylates myo-inositol 1 phosphate to a myo-inositol trisphosphate. An enzyme oxidizing 1L-myo-inositol 1 phosphate to an uronic acid derivative is found in the first two fractions. In the presence of ATP, Mg2+, Mn2+, and the second and the third enzyme fractions in an appropraite mixture, 1L-myo-inositol 1-phosphate can be phosphorylated to phytic acid. The structure of the trisphosphate acting as an intermediate is not yet known. PMID- 6250023 TI - [Mechanism of activating action of ATP on repair synthesis of DNA in chromatin]. AB - The mechanism of activating action of ATP on the repair synthesis of DNA was studied in the chromatin isolated from rat liver (G0). It was shown that chromatin catalyzed the conversion dNTP leads to dNDP leads to dNMP leads to NdR. The principal mechanism of activating action of ATP is the maintenance of dNTP levels. The maintenance is carried out mainly by the inhibition of dNTP's phosphatases and in less extent by the means of reaction dNDP leads to dNTP. Besides that, ATP partially suppresses 3' leads to 5' exonuclease of chromatin which degrades the nascent DNA. The activating action of ATP is connected neither with phosphorylation of histones, nor with the activities of ATP-dependent endo- or exonucleases, DNA gyrase, polynucleotide ligase, or DNA unwinding protein. PMID- 6250024 TI - [Cloning of fragments of lambda phage DNA, containing red and gam genes]. AB - On the base of plasmid pCV20 (Apr, Tcr mol. weight 5.2 x 10(6) a recombinant plasmid pEH60 (Apr, mol. weight 17.0 x 10(6) with BamHI fragment of phage DNA, containing red+ and gam+ genes was constructed. Selection was found on the ability of phage red- and gam- to propagate in strain E. coli K12 recA-, which was transformed by recombinant plasmid with active red and gam genes. Influence of recombinant plasmid pEH60 on processes of repair and recombination of phage lambda DNA and bacterial DNA was studied. It was shown that red gene in plasmid pEH60 compensates deficiency of redA gene in these processes with phage lambda DNA; in the case of E. coli K12 AB2480 uvr- recA- (pEH60) the processes of multiple reactivation and decombination of phage red- were presented. In the case of bacterial cells, plasmid pEH60 did not compensate deficiency of recA function of bacteria, although it partly compensates deficiency of recBC function. Increase of survival after introduction of plasmid pEH60 in the cell was obtained only for recBC- strain, but not for wild type and recA- strains. PMID- 6250025 TI - [Simian adenovirus 20 genome. I. DNA mapping using restriction enconucleases BamHI, EcoRi, XbaI, HindIII]. AB - The effect of specific restriction endonuclease on the simian adenovirus SV20 DNA was studied. It was shown that endonucleases SalI, XbaI, EcoRI, BamHI, HindIII cleaved the viral DNA into 3, 4, 5, 5, 8 specific fragments respectively. The sequence of fragments (physical map) was determined and found to be B-C-A for enzyme SalI, C-D-B-A--for enzyme Xbal, E-A-C-D-B--for enzyme EcoRI, B-E-C-A-D- for enzyme BamHI and B-E-A-C-(GH)-D-F--for enzyme HindIII. The G-C content of specific fragments was studied. The "right"-"left" orientation of the physical map of the simian adenovirus 20 DNA based on the G-C content was made in respect with the nomenclature of human adenoviruses. PMID- 6250026 TI - Hormonal control of lactation. PMID- 6250027 TI - [Disorders of bile secretion, Pathophysiological principles and therapeutic possibilities (author's transl)]. AB - A number of disturbing factors may lead to total impairment of bile secretion by altering the physical chemical properties, enzyme activites of the number of available receptors of the hepatocyte plasma membrane or raise the permeability of the biliary tract. Other disturbing factors change the composition of the bile and may consequently favor the formation of gallstones. More recent information on the formation of gallstones has led in a relatively short time to a better recognition, prophylaxis and therapy of individual disorders of bile secretion. Thus the tendency to form cholesterol concrements can be detected by investigating the bile. Knowledge of risk factors makes prophylaxis possible and today the pharmacological control of biliary lipid secretion permits drug therapy of certain forms of gallstones disorders. PMID- 6250028 TI - Research opportunities in alcoholism. PMID- 6250029 TI - Plasma-cell dyscrasia and peripheral neuropathy with a monoclonal antibody to peripheral-nerve myelin. PMID- 6250030 TI - Demyelinative neuropathy and myelin antibodies. PMID- 6250031 TI - Familial neonatal transient hypothyroidism due to maternal TSH-binding inhibitor immunoglobulins. PMID- 6250032 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 38-1980. PMID- 6250033 TI - Chromosomal action of ecdysone. PMID- 6250035 TI - Diurnal cycles in serotonin acetyltransferase activity and cyclic GMP content of cultured chick pineal glands. AB - Levels of serotonin N-acetyltransferase (NAT: acetul CoA:arylamine N acetyltransferase; EC 2.1.1.5.) activity in the chick pineal gland exhibit a marked diurnal variation in birds kept under a diurnal cycle of ilumination. Activity begins to rise rapidly at the start of the dark phase of the cycle and reaches maximum levels at mid-dark phase about 25-fold greater than the minimum basal level at mid-light phase. Thereafter, the level of activity declines to the basal level about the start of the light phase. This diurnal cycle in chick pineal NAT activity found in vivo has recently been reproduced in vitro with intact glands incubated in organ culture. The mechanism of the 'biological clock' which regulates these variations in level of chick pineal NAT activity is unknown. However, I now report that chick pineal glands cultured under a diurnal cycle of illumination exhibit a diurnal cycle in content of cyclic GMP which roughly parallels the cycles in NAT activity. In contrast, there was no correlation between variations in pineal content of cyclic AMP and in level of NAT activity. PMID- 6250034 TI - Expression of cloned beta-endorphin gene sequences by Escherichia coli. AB - DNA coding for the opiate peptide beta-endorphin has been cloned into bacterial plasmids in such a way as to direct the synthesis of a hybrid beta galactosidase/beta-endorphin protein. This hybrid protein can readily be cleaved in vitro to release biologically active beta-endorphin. PMID- 6250036 TI - Transformation of rat fibroblasts and formation of virus-induced syncytia. PMID- 6250037 TI - alpha-Actinin-containing branched microvilli isolated from an ascites adenocarcinoma. AB - Microvilli, slender projections approximately 0.1 micrometer in diameter which occur on the surfaces of many cell types, are bounded by plasma membrane except at the site of attachment to the cell body and contain microfilament bundle cores. The presence of both microfilaments and plasma membrane suggests the use of microbilli for investigations of membrane cytoskeleton interactions. Immunofluorescence studies with anti-alpha-actinin have suggested that alpha actinin is concentrated at the tips of intestinal brush border microvilli and might link actin microfilaments and the plasma membrane. However, this idea was disputed by later immunofluorescence and electrophoresis studies. To investigate the components and organization of microvilli from a less highly differentiated cell type, we have used an ascites sub-line (MAT-Cl) of a rat mammary tumour, the 13762 mammary adenocarcinoma, whose microvilli are high branched. Becaused such unusual structures may provide an understanding of cell-surface assemblies important in determining cell morphology, we have developed a procedure for isolating the branched microvilli and have shown that they contain significant quantities of alpha-actinin. PMID- 6250038 TI - Sequence of retrovirus provirus resembles that of bacterial transposable elements. AB - The nucleotide sequences of the terminal regions of an infectious integrated retrovirus cloned in the modified lambda phage cloning vector Charon 4A have been elucidated. There is a 569-base pair direct repeat at both ends of the viral DNA. The cell-virus junctions at each end consist of a 5-base pair direct repeat of cell DNA next to a 3-base pair inverted repeat of viral DNA. This structure resembles that of a transposable element and is consistent with the protovirus hypothesis that retroviruses evolved from the cell genome. PMID- 6250039 TI - Increased pulmonary alpha-adrenergic and reduced beta-adrenergic receptors in experimental asthma. PMID- 6250040 TI - F plasmid provides a function that promotes recA-independent site-specific fusions of pSC101 replicon. PMID- 6250041 TI - Alpha-Adrenergic receptors modulate beta-receptor affinity in rat kidney membranes. AB - Adrenergic receptors were first classified into two calsses--alpha and beta--on the basis of the relative pharmacological potencies of agonist compounds, and this classification has been supported by subsequent studies. In some tissues, such as the heart and liver, they exert similar physiological responses, and in other tissues, such as the uterus and vasculature, they have opposing roles. The occurrence of both classes of receptor in the same tissue lewwds to the problem of what determines whether the overall response observed is alpha-type or beta type, as adrenaline and noradrenaline bind to both receptor classes. Furthermore, direct binding studies have demonstrated that the two receptor classes are distinct and separate entities. We show here that stimulation of alpha-receptors in renal membranes causes a specific decrease in the affinity of the agonist compound isoprenaline for beta-receptors in the same membranes. This demonstrates that interactions occur between renal alpha- and beta-adrenergic receptors. Such interactions may modulate the response of the kidney to sympathetic stimulation. PMID- 6250042 TI - An unusual translocation of immunoglobulin gene segments in variants of the mouse myeloma MPC11. AB - Immunoglobulin light chain genes of the mouse are composed in germ-line DNA of four separate segments, the leader, V (variable), J (joining) and C (constant) segments. In immunocompetent cells a V and J gene segment are joined by a site specific recombination event. In variants of the mouse myeloma MPC11 a so-called kappa (k) light chain fragment is expressed which consists of the MOPC321 leader peptide, joined to the kappa constant region peptide. Using the Southern blotting technique we found that the gene coding for the light chain fragment has apkparently been generated by an aberrant translocation of a V gene segment identical or very similar to the MOPC321 V gene segment into the large intervening sequence between the J and the C gene segments. The resulting deletion of the splice signals of the J segments could be the reason for the observed splicing between leader and C region sequences, a phenomenon which may be of general interest for the understanding of the splicing mechanism. PMID- 6250043 TI - A new papillomavirus associated with alimentary cancer in cattle. PMID- 6250044 TI - A pyrimidine dimer-DNA glycosylase activity associated with the v gene product of bacterophage T4. AB - Mutations in the v gene of bacteriophage T4 are associated with a marked increase in sensitivity to killing by UV radiation at 254 nm, but not to a variety of other forms of base damage to DNA. Early studies from this laboratory provided evidence for a role of the v gene in the excision of pyrimidine dimers (PD) from DNA. Specifically, it was shown that extracts of T4v+-infected Escherichia coli catalyse the formation of single-strand breaks (nicks) and/or alkali-labile sites in UIV-irradiated duplex DNA. Comparable hydrolysis of phosphodiester bonds is not observed with extracts of E. coli infected with the mutant T4v1 (ref. 5). The product of the v gene has been extensively purified in a number of laboratories; however, convincing evidence of purification to physical homogeneity has not yet been presented. PMID- 6250046 TI - Special sites in genetic recombination. PMID- 6250045 TI - Calcium-induced decrease in membrane fluidity of sea urchin egg cortex after fertilization. AB - Fertilization of the sea urchin egg is a dramatic example of cell activation resulting from the interaction of an external stimulus, the spermatozoon, with the cell surface. Growing and quiescent cells may have different membrane states. Here we report membrne fluidity measurements on a surface membrane fraction, the cortex, isolated from unfertilized and fertilized eggs. The fluidity of the fertilized egg cortex, measured by electron spin resonance (ESR) spectroscopy using 5-doxylstearate as a probe, is less than that of the unfertilized cortex. In the intact egg the intracellular CA2+ to the cortex fraction isolated from unfertilized eggs triggers a fluidity decrease in vitro. The fluidity decrease seems to represent a Ca2+-induced change in membrane structure rather than a direct interaction of Ca2+ with phospholipid headgroups. PMID- 6250047 TI - Epidermal growth factor and mitogenesis. PMID- 6250048 TI - Invertible DNA determines host specificity of bacteriophage mu. AB - The function of the invertible G region of bacteriophage Mu is apparently to confer different host specificities on Mu. Two products of genes S and U, situated in the G region are not needed for the infectivity of Mu G(-) particles. In the Mu G(-) phage the S gene product and the 21-K polypeptide, presumably the product of gene U, are missing. Instead, two other polypeptides with different molecular weights are observed. PMID- 6250049 TI - A mouse alpha-globin-related pseudogene lacking intervening sequences. AB - A mouse alpha-globin-related pseudogene (psi alpha 30.5) completely lacks intervening sequences, and could not code for a functional globin poypeptide because of frameshifts. The widespread occurrence of globin pseudogenes in other species suggests that they are not 'dead' genes but may be important in controlling globin expression. PMID- 6250050 TI - Leukotriene B, a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes. AB - Arachidonic acid is metabolised either by cyclooxygenases to produce prostaglandins and thromboxanes or by lipoxygenases to produce mono-, di- and trihydroxyeicosatetraenoic acids (HETEs). Polymorphonuclear leukocytes (PMNs) release HETEs, including mono- and dihydroxy fatty acids, when exposed to stimuli such as the calcium ionophore A23187 (refs 1, 2). The mono-HETEs are assumed to be of particular importance with respect to effects on leukocyte function because they have been shown to possess both chemotactic and chemokinetic activities towards PMNs and eosinophils. However, we have now shown that the chemokinetic and aggregating activities released from rat and human PMNs exposed to ionophore A23187 (ref. 5) are not due to the release of mono-HETEs but to that of 5, 12-di HETE (leukotriene B). This compound is active over the concentration range 10 pg ml-1 to 5 ng ml-1. PMID- 6250051 TI - Increased proton conductance pathway in brown adipose tissue mitochondria of rats exhibiting diet-induced thermogenesis. AB - It has recently been demonstrated that in rats induced to overeat by being fed a varied and palatable diet (the 'cafeteria diet') there is a marked increase in heat production which serves to reduce, or prevent, the development of obesity. This diet-induced thermogenesis is associated with increases in sympathetic activity, and with changes in brown adipose tissue. Following cafeteria feeding, brown adipose tissue hypertrophies and and exhibits increased lipolysis and an apparently greater thermogenesis in response to noradrenaline. These metabolic changes resemble those seen during non-shivering thermogenesis in cold-adapted rats, and it was proposed that non-shivering thermogenesis and diet-induced thermogenesis have a similar metabolic origin which depends on the unique capacity of brown adipose tissue for thermogenesis. During non-shivering thermogenesis heat is produced in brown adipose tissue through a proton conductance pathway across the inner mitochondrial membrane that dissipates the proton gradient generated by respiration. The activity of the proton conductance pathway can be modulated by purine nucleotides, and changes in the pathway seem to be related to the level of purine nucleotide binding to brown adipose tissue mitochondria. We now report results which indicate that the proton conductance pathway is augmented in cafeteria-fed rats, and suggest that it operates to dissipate their excess energy intake through diet-induced thermogenesis PMID- 6250052 TI - Insulin stimulates sugar transport in giant muscle fibres of the barnacle. AB - Insulin stimulates sugar transport in vertebrate skeletal muscle but the mechanism of insulin action is unknown. It has been reported that Na transport in giant muscle fibers of the barnacle (Balanus nubilis) is sensitive to insulin but no one has examined the sensitivity of sugar tansport to insulin in this preparation. We show here that insulin does, indeed, stimulate sugar transport in barnacle muscle. The great advantage of barnacle muscle over all other muscles used so far for investigating the mechanism of insulin action is its large size, which facilitates measurements on single cells and permits the experimenter to control the intracellular environment of the muscle fibre by the technique of internal dialysis. Using single muscle fibres it is possible to show that acceleration of sugar transport by insulin is associated with a fall in ionized Ca, a fall in cyclic AMP and a rise in cyclic GMP. Working with internally dialysed muscle fibres we find that insulin only increases sugar transport when the dialysis solution contains ATP. In the absence of insulin, sugar transport is dialysed muscle is increased by a rise in ionized Ca, a fall in cyclic AMP and, when the internal Ca is elevated, by a rise in cyclic GMP. PMID- 6250053 TI - An effect of chloride on (Na+K) co-transport in human red blood cells. AB - In certain conditions, internal K can stimulte active Na:K transport as well as Na:Na exchange through the ouabain-sensitive Na, K exchange pump. When the exchange was examined during a study of the action of internal K, it emerged that the removal of K0 (the main requirement for Na:Na exchange) reduced the ouabain insensitive Na efflux. Thus, in eight experiments done variously with outdated cells or high and low [K]i, PCMBS-treated cells, the K0-dependent Na efflux ranged from 0.18 to 0.70 muEquiv per ml cells per h. This conflicts with the well established view that the K0-dependent and ouabain-sensitive components of Na efflux are identical. However, the K0-dependent, ouabain-insensitive Na efflux was found to go through the (Na+K) co-transport system, which was further found to show a dependence on chloride ions. PMID- 6250054 TI - Molecular heterogeneity of benzodiazepine receptors. AB - Benzodiazepines exhibit reversible, stereospecific high affinity binding to mammalian brain membranes, and the respective binding sites for 3H-flunitrazepam represent pharmacologically and clinically relevant receptors for benzodiazepines. Recently it has been demonstrated that reversibly bound 3H flunitrazepam becomes irreversibly attached to a specific membrane protein with apparent molecular weight of 50,000 when incubations are performed in the presence of UV light. Irreversible binding of 3H-flunitrazepam to this protein had pharmacological properties similar to reversible benzodiazepine receptor binding, indicating that 3H-flunitrazepam is a photoaffinity label for the benzodiazepine receptor. Using irreversible binding of 3H-flunitrazepam and subsequent electrophoretic separation of the labelled proteins in SDS-gels followed by fluorography, we found that in hippocampus and several other brain regions at least two different types of benzodiazepine receptors exist. Each seems to be associated with a gamma-aminobutyric acid (GABA) receptor. PMID- 6250055 TI - Evidence against presynaptic alpha-adrenoreceptor modulation of cardiac sympathetic transmission. PMID- 6250056 TI - Open time of channels activated by binding of two distinct agonists. PMID- 6250057 TI - Proton NMR detection of acetylcholine status in synaptic vesicles. AB - The storage granules of cholinergic nerve terminals, the synaptic vesicles, have a central role in the mechanism of cholinergic transmission, and direct evidence as to whether acetylcholine is stored in them in a free or partially immobilized form is therefore of interest. In some secretory systems it has become evident that low molecular weight secretion products are stored within the granules as complexes with proteins or proteoglycans. The application of high resolution NMR spectroscopy to isolated granules has recently elucidated the internal structure of secretory granules. We report here that proton NMR analysis of isolated cholinergic synaptic vesicles from Torpedo marmorata allows the identification of acetylcholine within the organelle. The spectrum shows that all the acetylcholine is dissolved in an essentially fluid phase within the core. Vesicular and uncompartmentalized acetylcholine can be distinguished from each other and in addition, any hydrolysis to choline and acetate can be monitored. The results open the possibility of studying dynamics of acetylcholine pools and their breakdown in cholinergic tissue by a direct and non-perturbing method. PMID- 6250058 TI - Structure of cytochrome c': a dimeric, high-spin haem protein. PMID- 6250060 TI - Evolution of bacterial cytochromes c2. PMID- 6250059 TI - Molecular dynamics of ferrocytochrome c. PMID- 6250061 TI - Malignant transformation and protein phosphorylation. PMID- 6250062 TI - Insertion of the eukaryotic transposable element Ty1 creates a 5-base pair duplication. AB - The his4-912 mutation results from insertion of a transposable element into the 5'-non-coding region of the his4 gene of yeast. A duplication of 5 base pairs of wild-type his4 DNA flanks the inserted element. The major class of His+ revertants result from excision of most of the transposable element, leaving an inserted segment of 334 base pairs flanked by the 5-base pair repeats. PMID- 6250063 TI - Co-infection by lactic dehydrogenase virus and C-type retrovirus elicits neurological disease. AB - Intraperitoneal injection of neuropathogenic strains of lactic dehydrogenase virus (LDV) causes a histologically distinctive fatal paralytic disease characterized by an inflammatory destruction of motor neurones in the brain stem and cord in C58 mice aged over 9 months. To elicit the disease in the naturally susceptible C58 strain requires an age-associated or X-ray induced loss of immunological competence, LDV infection and genetic susceptibility. Genetic studies of the common inbred mouse strains showed that susceptibility to the disease was not linked to the major histocompatibility complex but correlated with the FV-1n allele, susceptibility to spontaneous leukaemia, and infection by neuropathogenic strains of LDV. These observations suggested that neuropathogenic strains of LDV elicit the disease only in those strains of mice that carry multiple copies of N-tropic C-type retroviruses in their genomes and that are permissive for retrovirus replication. Presumably the expression of these viral genomes (high titres of virus in tissues correlating with age) is the important factor. Here we present genetic evidence to support this hypothesis and briefly discuss the possible implications. PMID- 6250064 TI - Feline sarcoma virus polyprotein P115 binds a host phosphoprotein in transformed cells. AB - Several independent isoltes of feline sarcoma virus (FeSV) have been described. Such viruses are apparently derived by genetic recombination between feline leukaemia virus (FeLV) genomic RNA and host cellular genetic sequences with transforming potential. Two FeSV isolates, one originally described by Gardner and the second by Snyder-Theilen, have been shown to encode polyproteins of around 115,000 molecular weight. Both polyproteins contain FeLV structural components (p15, p12) at their amino terminus in addition to nonstructural carboxyl terminal components encoded by acquired sequences within the FeSV genome. We have previously shown that Gardner FeSV P115 contains multiple sites of phosphorylation within its nonstructural component and possesses an associated protein kinase activity. In the present study we describe the expression in cells derived from a number of mammalian species, of a highly conserved celklular phosphoprotein with binding affinity for Gardner FeSV P115. This protein, designated P150, exhibits an associated protein kinase activity and is immunologically and structurally distinct from polyproteins encoded by the Gardner or Snyder-Theilen strains of FeSV. PMID- 6250065 TI - The yeast transposon Ty1 generates duplications of target DNA on insertion. PMID- 6250066 TI - The caries resistance of human teeth is determined by the spatial arrangement of hydroxyapatite microcrystals in the enamel. AB - Teeth from different people differ in their susceptibility to caries. The beginning and the development of tooth decay depend on the presence of bacterial plaque and on the structure of the tooth enamel. But it has not been established whether the organic or the inorganic component of the enamel (which is comprised principally of hydroxyapatite microcrystals organized in a firm matrix), is responsible for most of the resistance of teeth to caries. We report here that the electron spin resonance (ESR) lines of the (CO3)3 defect of samples of enamel prepared from caries-resistant teeth differ significantly from the corresponding spectra of the caries-sensitive samples. We have traced these differences to the hydroxyapatite microcrystalline alignment in the tooth enamel, and found that this alignment is specific to individuals and is therefore probably nutritionally or genetically determined. PMID- 6250067 TI - Gametocytogenesis by malaria parasites in continuous culture. AB - Asexual proliferation of malaria parasites proceeds by multiplication of the parasites within red cells. Following rupture of the host cells the released merozoites re-invade other red cells. On re-invasion, a proportion of merozoites become, not asexual parasites but gametocytes, the sexual stages infective to the mosquito vectors. Conversion of asexual parasites to gametocytes occurs not only during natural infections but also in continuous in vitro culture as reported first by Trager and Jensen and by others. We showed previously that the proportion of early intra-erythrocytic stages (ring stages) of Plasmodium falciparum which developed into gametocytes in culture was influenced by culture conditions. Gametocyte formation was rare in conditions supporting rapid proliferation but frequent when parasite densisites were static. We now show that nearly 100% of ring stages develop into gametocytes in response to 1mM cyclic AMP in static cultures whereas in rapidly growing cultures few rings become gametocytes in response to cyclic AMP. PMID- 6250068 TI - Interaction of anaesthetics with electrical synapses. AB - Studies of the interaction of anaesthetics with various preparations, from whole animals to organic solvents, have been continuing since Overton and Meyer found a correlation between anaesthetic potency and solubility in olive oil. Although the physiological basis of anaesthesia is far from clear, one popular hypothesis is that anaesthetics act primarily by interfering with the normal functioning of chemical synapses. This hypothesis is supported by experiments showing that these synapses are more sensitive to both local and general anaesthetics than are axons. The effects of anaesthetics on electrical synapses (gap-junctions or nexus) have not previously been studied. These ubiquitous structures, presumably responsible for cell-to-cell communication, are found in most vertebrate and invertebrate tissues. We report here the effects of several anaesthetics on electronic coupling between nerve cells, and show that electrical synapses are less sensitive to most anaesthetics than are chemical synapses and axonal membranes. PMID- 6250069 TI - Abelson murine leukaemia virus transformation involves loss of epidermal growth factor-binding sites. AB - Malignant transformation by mammalian RNA sarcoma viruses has previously been shown to involve a reduction in receptor sites for a well characterized 6,000 molecular weight (MW) growth-promoting substance, designated epidermal growth factor (EGF). Although Abelson murine leukaemia virus (AbLV) resembles sarcoma viruses in its ability to transform embryo fibroblasts in cell culture, AbLV induces a rapid B-cell lymphoid leukaemia rather than fibrosarcomas in vivo. The major translational product of AbLV is a highly phosphorylated polyprotein of MW 120,000 which exhibits an associated tyrosine-specific protein kinase activity and probable transforming function. We show here that AbLV transformation resembles transformation by RNA sarcoma viruses with respect to the abolition of EGF-binding sites. EGF binding is restored to control levels following loss of polyprotein expression in morphological revertants of AbLV-transformed clones and remains uninfluenced in cell lines infected with transformation-defective (td) AbLV mutants encoding polyproteins deficient in protein kinase activity. These findings indicate that AbLV transformation involves a polyprotein-associated, tyrosine-specific protein kinase activity which mediates its effect through a mechanism resulting directly or indirectly in the abolition of EGF-binding sites. PMID- 6250070 TI - DNA cloning in Streptomyces: resistance genes from antibiotic-producing species. AB - The biochemical and morphological differentiation of actinomycetes makes them academically and economically interesting. Their secondary metabolites provide the majority of medically and agriculturally important antibiotics (streptomycete genes may also be the primary source of clinically important antibiotic resistance); their complex morphological developmental cycle involves a series of changes from vegetative mycelial growth to spore formation. Recombinant DNA technology would add a powerful new dimension to the analysis of these various aspects of actinomycete biology and would also facilitate the development of industrial strains with increased antibiotic yield, or capable of making new antibiotics. For most of these purposes, cloning of genes within and between actinomycetes is required to study the expression of particular genes in genetic backgrounds defined by mutations of the characters under study. To achieve this, we have now developed a method for molecular cloning involving the transfer of genes between unrelated streptomycetes. PMID- 6250071 TI - DNA cloning in Streptomyces: a bifunctional replicon comprising pBR322 inserted into a Streptomyces phage. AB - The Gram-positive, mycelial, differentiating streptomycetes are responsible for the production of many important antibiotics. The availability of gene cloning systems in this microbial group would have many industrial applications besides allowing more penetrating study of the genetics of Streptomyces coelicolor A3(2) (which, as the best understood streptomycete genetically, serves as a model for much other Streptomyces genetics). Recent successes (see previous paper) in introducing Streptomyces DNA into S. coelicolor and Streptomyces lividans on plasmid vectors would be nicely complemented by the availability of Streptomyces bacteriophage vectors (discussed in ref. 5): for example, many phages have wide and easily defined host ranges; heat-inducible prophages might be used to give high copy number of cloned DNA; efficient phage promoters might be used to increase gene expression; there may be differential stabilities for particular DNA sequences cloned in plasmids vis-a-vis phages; selective insertion of DNA, utilizing packaging constraints, may be possible with phages; and in situ hybridization of radioactive probes to DNA in plaques is likely to be simple. We describe here the use of the moderately wide host range temperate phage, phi C31, for this purpose. PMID- 6250072 TI - Novobiocin inhibition of simian virus 40 DNA replication. PMID- 6250073 TI - Identification of integrated hepatitis B virus DNA and expression of viral RNA in an HBsAg-producing human hepatocellular carcinoma cell line. PMID- 6250074 TI - Presence of integrated hepatitis B virus DNA sequences in cellular DNA of human hepatocellular carcinoma. AB - Hepatitis B virus (HBV) may be one of the agents involved in the aetiology of human primary liver cancer. This hypothesis is supported by (1) the similarity between the geographical distribution of chronic carriers of the viral surface antigen (HBsAg) and that of hepatocellular carcinoma (HCC); (2) the increase in the prevalence of HBV markers in serum of patients with primary liver cancer when compared with the general population; (3) the observation that HBV infection precedes the development of the tumour. Moreover, these epidemiological indications of an association between HBV infecton and hepatocellular carcinoma are supported by the detection of HBV markers such as HBsAg or viral DNA sequences, although in a non-integrated form in tumour tissue. To study the relationship between HBV and primary liver cancer further, we looked for the presence of free or integrated viral DNA in tumour tissue of human hepatocellular carcinomas and in a HBsAg-producing human hepatoma cell line. Using the blot transfer hybridization technique and cloned HBV DNA as a probe, we have now demonstrated that the viral DNA is integrated in the cellular genome both in tumour tissue and in a hepatoma cell line. PMID- 6250076 TI - Membrane protein distributors. PMID- 6250075 TI - Integration of hepatitis B virus sequences and their expression in a human hepatoma cell. AB - Hepatitis derived from hepatitis B virus (HBV) infection is endemic throughout the world, but it is particularly prevalent in Asia and Africa. In these areas, demographic studies show a strong coincidence between HBV infection (assayed by HBV antigenic markers) and the incidence of primary liver cancer. On these grounds, a causal link between HBV infection and primary hepatocellular cancer has been proposed. Recently, a human hepatoma cell line (PLC/PRF/5; Alexander cells) has been shown to produce hepatitis B surface antigen (HBsAg). We show here that the Alexander cell line contains at least six (four complete and two partial) hepatitis B viral genomes integrated into high molecular weight host DNA. An analysis using specific probes to fragments of the HBV genome suggests that integration of the virus in most cases occurs at the nicked cohesive end region of the virus. Expression of viral sequences using Northern blots demonstrates the presence of RNA transcripts specific for the surface antigen sequences of HBV DNA and the absence of detectable transcripts corresponding to the hepatitis B core antigen. PMID- 6250077 TI - Ethyl beta-carboline-3-carboxylate shows differential benzodiazepine receptor interaction. AB - High-affinity binding of 3H-diazepam and 3H-flunitrazepam has provided evidence for the presence of benzodiazepine receptors on brain neurones. Pharmacological evidence showing a clear correlation between receptor affinity and in vivo pharmacological potency for several benzodiazepines and a link between benzodiazepine receptors and GABA (gamma-amino-butyric acid) receptors at the molecular level, indicates that these receptors are relevant to the pharmacological and clinical effects of benzodiazepines. In searching for possible endogeneous ligands for benzodiazepine receptors we have recently isolated ethyl beta-carboline-3-carboxylate (beta-CCE) found human urine and brain, and shown that beta-CCE has a higher affinity than diazepam for brain benzodiazepine receptors. beta-CCE itself is probably not present in the brain, but may be closely related to an endogenous benzodiazepine receptor ligand. We report here that beta-CCE, in contrast to benzodiazepines, can distinguish clearly between benzodiazepine receptors in cerebellum and hippocampus. This result strongly indicates that benzodiazepine receptors are not a single class of non-interacting entities. It has not been possible to determine whether two distinct receptors are present and/or whether true negative cooperativity exists among hippocampal, but not cerebellar, benzodiazepine receptors. PMID- 6250078 TI - Adrenal corticoids regulate sensitivity of noradrenaline receptor-coupled adenylate cyclase in brain. PMID- 6250079 TI - Elution of herpes simplex virus-specific cytotoxic antibodies from squamous cell carcinoma of uterine cervix. AB - There is evidence that carcinoma of the cervix uteri is associated with infection with herpes simplex virus type 2 (HSV-2), and although indirect evidence suggests an aetiological relationship, this remains controversial. One facet of the problem is that complement-dependent cytotoxic antibodies is HSV-2-infected cells have been undetectable or found only in low titre in sera from patients with progressive cervical cancer whereas higher titres have been found where cervical lesions are less advanced. Indeed, cytotoxic antibody titres have been found to rise during the follow-up period after successful treatment. Absorption of these antibodies by the tumour cells has been proposed as a possible reason for low HSV 2 cytolytic reactivity in patients with progressing cervical cancer. This explanation assumes the presence of HSV-2-specific antigen(s) on the tumour cells. We now provide support ffor this assumption with evidence that absorbed HSV-2-specific antibodies can be eluted from cervical cancer tissue. PMID- 6250080 TI - Modulation of brain polyphosphoinositide metabolism by ACTH-sensitive protein phosphorylation. AB - Phosphorylation of membrane components is thought to be an important process in membrane function. Phosphorylated proteins and a special class of phospholipids, the (poly)phosphoinositides (poly PI), are implicated in the regulation of membrane permeability and synaptic transmission in neurones. For many years, protein phosphorylation and poly PI metabolism have been studied in parallel without knowledge of their possible interaction. We report here that the ACTH sensitive protein kinase/B-50 protein complex which we recently isolated in soluble form from rat brain synaptosomal plasma membranes has lipid phosphorylating activity. Exogenously added phosphatidylinositol 4-phosphate (DPI) is phosphorylated to phosphatidylinositol 4,5-diphosphate (TPI), and this DPI-kinase activity is dependent on the state of phosphorylation of the protein kinase/B-50 protein complex. The results imply that phosphorylation of protein may affect the metabolism of (poly) PI in brain cell membranes. PMID- 6250081 TI - Rescue of a splicing defective mutant by insertion of an heterologous intron. PMID- 6250082 TI - Nucleosome assembly. AB - Histones and DNA can spontaneously associate to form the nucleosome subunits of eukaryotic chromatin, but two proteins which occur in the eukaryotic nucleus can facilitate nucleosome assembly and greatly extend the conditions which permit assembly to occur. Recently several laboratories have reported new experimental systems which help to analyse, reconsruct and exploit the cellular mechanisms of chromatin assembly. PMID- 6250083 TI - Genetic alteration of nerve membrane excitability in temperature-sensitive paralytic mutants of Drosophila melanogaster. PMID- 6250084 TI - Sodium ions increase the affinity of clonidine for alpha 1-adrenoceptors in rat brain. AB - alpha 1-Adrenoceptors in rat brain membranes, labeled by the antagonist [3H] prazosin, increase their affinity for clonidine several-fold when sodium ions are added. The conversion of alpha 1-adrenoceptors, buy sodium ion, into a conformation, which has higher affinity for the agonist clonidine, indicates that these receptors as the alpha 2-adrenoceptors are modulated by cations in vitro. PMID- 6250086 TI - The positive inotropic, antiarrhythmic and Na+, K+-ATPase inhibitory effects of the isoquinoline derivative BIIA. PMID- 6250085 TI - The time course of changes in cyclic nucleotide levels during cholinergic inhibition of positive inotropic actions of isoprenaline and theophylline in the isolated canine ventricular myocardium. PMID- 6250087 TI - Effects of Goniopora toxin on guinea-pig blood vessels. AB - Effects of a marine polypeptide, Goniopora toxin (GPT) (molecular weight 12,000), were examined in isolated blood vessels guinea pigs. GPT, ranging from 10-100 nM, augmented the contractile response to electrical transmural stimulation in the thoracic aorta, portal vein, and mesenteric and femoral arteries. The effects were abolished by tetrodotoxin and bretylium, and were markedly attenuated by phentolamine. As GTP did not affect the resting tension spontaneous rhythmicity or noradrenaline-induced contraction, the toxin appears to act on the neural elements in the vascular wall rather than on the smooth muscle. In the portal vein preloaded with 3H-noradrenaline, GPT enhanced the 3H-efflux in response to electrical transmural stimulation, yet had not effect on the spontaneous efflux. The increase in stimulation-evoked 3H-efflux caused by GPT was more than 15 times larger than the increase seen with cocaine or phentolamine. Tetrodotoxin completely blocked the 3H-efflux induced by electrical transmural stimulation. These data suggest that GPT acts on nerve components in guinea pig blood vessels and increases the release of noradrenaline evoked by electrical stimulation of the nerve fibers. These effects are probably associated with prolongation of the action potential duration and repetitive discharges in the adrenergic nerve fibers. PMID- 6250088 TI - Enhanced behavioural, electrocortical and hyperthermic effects of serotonin-like agents after impairment of serotonin transmission in fowl brain. AB - In adult fowls and in young chicks (Gallus domesticus) the effects were studied on body temperature, behaviour and electrocortical activity of 5-HT and other direct or indirect serotonin agonists given into the III cerebral ventricle in conditions of prolonged impairment of serotoninergic transmission. In chicks pretreated with 5,6-dihydroxytryptamine the subsequent intraventricular injection of 5-HT produced more intense and longer-lasting hyperthermic response and behavioural and electrocortical sleep. On the other hand fenfluramine given intraventricularly in fowls pretreated with 5,6-DHT did not produce significant body temperature and behavioural changes. After 14 and 21 day treatment with methysergide the subsequent administration of 5-HT, fenfluramine and quipazine produced in fowls an hyperthermic response and behavioural sleep more marked and longer-lasting than in control animals. The present experiments show that in conditions of chronic impairment of 5-HT function there is an enhanced behavioural and body temperature response to 5-HT and drugs acting by releasing endogenous 5-HT or 5-HT agonists. PMID- 6250089 TI - [Regulation of the cerebral circulation]. PMID- 6250091 TI - [Slow inactivation of incurrent channels of the electroexcitable membranes of mollusk central nervous system neurons]. PMID- 6250090 TI - [Effect of prostaglandins F2alpha and E2 on the sensitivity of rabbit cerebral cortex neurons to acetylcholine and noradrenaline]. AB - Effects of microiontophoretically applied prostaglandins F2 alpha and E2 on the activity pattern and sensitivity of single neurons to acetylcholine and norepinephrine were investigated in the rabbit somatosensory cortex. F2 alpha generally inhibited and E2 increased the firing rate of the neurons. F2 alpha usually changed the sensitivity of the neurons acetylcholine, while E2 realized its effects upon norepinephrine-sensitive units. F2 alpha influence on the excitatory effects of acetylcholine and E2 influence on the norepinephrine inhibition were characterized as a rule by decreasing the mediator actions or by changing the initial responses sign to the opposite one. It is assumed that prostaglandins of group F take part in cholinergic transmission while those of group E -- in the adrenergic transmission. The investigated prostaglandin action is likely to be realized by selective inhibition of the adenilate or guanilate cyclase activity with subsequent decrease in synthesis of cyclic adenosine monophosphate and cyclic guanosine monophosphate. PMID- 6250092 TI - Specific binding of kainic acid to purified subcellular fractions from rat brain. AB - The subcellular distribution of kainic acid (KA) binding sites in rat brain has been studied using a microcentrifugation assay. KA did not bind to myelin or brain cytosol and had few or no binding sites in the nuclear fraction. However, it bound to microsomal components (Kd = 128-136 nM; 2.5-4.8 pmol/mg protein), purified synaptic plasma membranes (SPM)(Kd = 45-71 nM; 5.8-6.5 pmol/mg), and purified cell-body and intraterminal mitochondria (Kd = 11-31 nM; 0.4-1.1 pmol/ng). Bound KA could be totally displaced by L-glutamate or L-asparate, but several putative antagonists of these amino acids (nuciferin, compound HA-966, 2 amino-4-phosphonobutyrate, and 2-amino-3-phosphonoproprionate) failed to displace KA or did so at very high concentrations (greater than or equal to 4 mM). Glutamic acid diethyl ester (GDEE) and D,L-alpha-aminoadipate (alpha-AA) were more effective (IC50, 0.2-0.8 mM) and showed differential effects in their capacity to displace KA bound to the various subcellular fractions. Thus, GDEE only displaced 40-60% of the KA bound by SPM or mitochondria and did not prevent the binding of KA to microsomes. alpha-AA, on the other hand, was more effective in preventing the binding of KA at high concentrations and displaced between 80 and 100% of the drug. Both compounds showed biphasic curves of KA displacement from synaptic plasma membranes and mitochondria. The overall results indicate the presence of multiple binding sites for KA in brain cells and suggest that KA does not act exclusively as synaptic glutamate receptors. The mechanism of KA action is most likely quite complex, and the drug probably acts at multiple binding sites affecting a number of processes. PMID- 6250094 TI - Further ultrastructural observations of virus morphogenesis and myelin pathology in JHM virus encephalomyelitis. AB - Groups of 3, 17, and 28-day-old Swiss mice were inoculated intracerebrally with JHM virus, the neurotropic strain of mouse hepatitis virus (MHV), and studied serially by virologic and morphologic techniques. Beginning 2--5 days post inoculation, all groups of infected mice developed CNS lesions which were destructive in the 3-day-old group and demyelinative in the 17 and 28-day-old animals. Infectious virus could be isolated from the brain, spinal cord, and liver. Electron microscopy demonstrated the virus to be pantropic in the CNS with virions occurring within ependymal cells, astrocytes, neurons, oligodendrocytes, endothelial cells, and cell of haematogenous origin. Giant cell formation was a constant feature. In regions of demyelination, oligodendrocytes exhibited a propensity to proliferative aberrant membrane. Myelin degradation was accompanied by membrane vesiculation and by the stripping action of macrophages. The lesions were not due to CNS elements in the inoculum since in animals inoculated with normal CNS suspensions from appropriate age groups failed to show lesions. The morphogenesis of JHM virions was followed ultrastructurally as was the formation of syncytia in the different cell types. In addition to delineating virus morphogenesis and myelin pathology, the results underscore the pantropic nature of JHM virus in the CNS, the synstemic nature of the infection, and that oligodendrocytes were the principal targets. PMID- 6250093 TI - Calmodulin in brain of schizophrenics. AB - A heat-stable Ca2+-dependent regular protein with the characteristics of calmodulin was extracted and purified from striatum and cerebral cortex of autopsied human brains. The human calmodulin preparation cross-reacts with Ca2+ dependent phosphodiesterase isolated from rat, bovine, and human cerebral cortex. There was no significant difference between calmodulin content measured in membranes obtained from striatum or cortex of nine control subjects without a psychiatric history and seven schizophrenic individuals. PMID- 6250095 TI - Alterations in beta-endorphin-induced locomotor activity in morphine-tolerant rats. PMID- 6250096 TI - Interaction of nerve growth factor with pheochromocytoma cells. Evidence for tight binding and sequestration. PMID- 6250097 TI - Calcium ionic channels in electrically excitable membrane. PMID- 6250098 TI - Cyclic nucleotides in the rat caudate-putamen complex: histochemical characterization and effects of deafferentation and kainic acid infusion. PMID- 6250099 TI - Aminopyridines and synaptic transmission. PMID- 6250100 TI - Extracellular potassium accumulation and transmission in frog spinal cord. PMID- 6250101 TI - Subcellular distribution of adenylate cyclase and cyclic adenosine monophosphate phosphodiesterase in rat and guinea-pig deferens. PMID- 6250102 TI - Autoanalgesia: opiate and non-opiate mechanisms. AB - Autoanalgesia (behaviorally-activated antinociception) was elicited by lesion induced hyperemotionality or the classical conditioning of fear to the environmental stimuli associated with measuring antinociception. Both hyperemotionality and antinociception exhibited parallel decline in septal lesioned rats with daily handling and in VMH-lesioned rats following treatment with diazepam. Autoanalgesia elicited by conditioned fear was blocked by spinal cord transection but not by diazepam. Although opiate binding experiments suggested the involvement of endorphins as mediators of autoanalgesia, hypophysectomy, morphine tolerance or very high doses of opiate antagonists failed to reduce the antinociception. Electrolytic lesions of the nucleus raphe magnus, a descending serotonergic system, did cause a significant reduction in autoanalgesia. Therefore, endorphin systems may be activated by the stress involved in autoanalgesic paradigms as a parallel system, whose functional integrity is not necessary for the expression of behaviorally-induced antinociception. PMID- 6250103 TI - The role of endorphins in animal learning and behavior. AB - The present review examined the influence of endorphins in animal learning and behavior. It was suggested that in learning paradigms involving stress, the stressor elicits the release of endorphins. Given the evidence on endorphin mediated, stress-induced analgesia, it was further suggested that the stress induced release of endorphins modulates the aversiveness of the stressor, and as such, affects the learning based on this stressor. A number of learning paradigms, e.g., the conditioned emotional response, preference for signaled shock, conditioned taste aversions, and learned helplessness, were presented in support of this mediation of learning by the endorphins. A possible interaction between the endorphins and adrenocorticotropic hormone was offered as a physiological basis for this mediation. PMID- 6250104 TI - The role of endorphins in stress: evidence and speculations. AB - Several lines of evidence suggest that the endogenous opioid peptides endorphins may play a role in the defensive response of the organism to stress. The present paper summarizes these findings as well as evidence linking endorphins to the anterior pituitary polypeptide hormone adrenocorticotropin (ACTH). Evidence is presented that endorphins may function as trophic hormones in peripheral target organs such as the adrenal medulla and the pancreas. As such they may be part of the physiological mechanisms that mediate adrenaline and glucagon release in response to stress. Endorphins (enkephalins) are also suggested to play a role in the control of the pituitary gland during stress. In such capacity they may act as hormone-releasing or inhibiting factors. Finally, endorphins appear to play a role in the behavioral concomitants of stress. In such capacity endorphins are suggested to function as modulators of neural systems that mediate the elaboration and expression of the reactive/affective components of stress. Speculations on the mode of interaction between endorphins and ACTH in the global response to stress are discussed. PMID- 6250105 TI - Bilateral mammary carcinoma; immunologic implications. PMID- 6250106 TI - The antiemetic activity of tetrahydrocannabinol versus metoclopramide and thiethylperazine in patients undergoing cancer chemotherapy. AB - A double blind-cross-over randomised clinical trial has been conducted to compare the antiemetic effects of tetrahydrocannabinol, thiethylperazine and metoclopramide. There were no significant differences in the antiemetic effects of these drugs. The incidence of adverse reactions as recorded by both the staff and the patients was significantly higher in the tetrahydrocannabinol group than in either the metoclopramide or thiethylperazine groups. This trial has established that in the dosages used tetrahydrocannabinol given by mouth has an antiemetic effect of approximately the same order as thiethylperazine and metoclopramide. However, its adverse effects are sufficiently greater than those of the other agents to prevent is widespread usage for this purpose. Tetrahydrocannabinol taken by mouth is not recommended as a routine antiemetic agent in cancer chemotherapy. PMID- 6250107 TI - The control of uterine activity. PMID- 6250108 TI - Viral infections in obstetrics and gynecology. PMID- 6250109 TI - [Herpes simplex virus types I and II in experimental eye infections]. PMID- 6250110 TI - [Blast transformation reaction in ophthalmic herpes]. PMID- 6250111 TI - Simultaneous primary oat cell carcinoma (apudoma) and squamous cell carcinoma of the hypopharynx. AB - The first case of the association of oat cell carcinoma and squamous carcinoma of the hypopharynx occurring in a 57-year-old man is reported. The patient underwent total laryngopharyngectomy with radical neck dissection, but died 3 1/2 months after diagnosis with multiple bone metastases of the ribs and vertebrae. The histogenesis of oat cell carcinoma in the hypopharynx is discussed, together with the therapeutic approach for the simultaneous occurrence of two primary malignant neoplasms in the same organ. PMID- 6250113 TI - Primary Ewing's sarcoma of the mandibular ramus: a case report. AB - Primary Ewing's sarcoma of the mandible is an exceedingly rare finding in the practice of otolaryngology. A case of this neoplasm occurring as a parotid mass is presented. It represented a diagnostic dilemma because of its elusive histopathologic findings. The gross and clinical appearances, microscopic findings, differential diagnosis, and prognosis of this neoplasm are discussed. PMID- 6250112 TI - Nasopharyngeal mucormycotic osteitis: a new syndrome characterized by initial presentation of multiple cranial nerve palsies. AB - Rhinocerebral mucormycosis, a highly lethal fungal infection of the head and neck, is commonly recognized by its classic appearance. Two cases of this newly recognized clinical syndrome with isolated unilateral peripheral cranial nerve V, VI, VII, IX, X, XI, and XII palsies and initial sparing of the eighth cranial nerve are presented. Examination revealed that each patient had ulceration of the nasopharynx and osteitis of the base of the skull. Nose, orbits, paranasal sinuses, and intracranial nervous systems were initially spared. The cause of this obscure cranial nerve paralysis was diagnosed from biopsy specimens of the nasopharyngeal tissues and the demonstration of nonseptate hyphae. Review of the literature did not indicate that this syndrome had previously been recognized. The name nasopharyngeal mucormycotic osteitis is suggested. PMID- 6250114 TI - Synovial cell sarcoma. AB - Synovial sarcoma of the head and neck is a rare lesion. Based on previous literature reports, these lesions carry a poor prognosis. Case reports of two patients diagnosed and treated recently for head and neck lesions of this type are presented. A review of pathologic sections at the Armed Forces Institute of Pathology (AFIP) suggests that this lesion is more colmon than believed previously. PMID- 6250115 TI - Behavioral and electrophysiological effects of various types of peripheral nerve lesions in the rat: a comparison of possible models for chronic pain. AB - Three types of nerve lesions involving the brachial plexus were produced in rats: (1) multiple dorsal rhizotomy; (2) spinal nerve section just distal to the dorsal root ganglia (DRG); (3) section of the median, ulnar and radial nerves. The 3 types of lesion caused self-mutilation (autotomy) of the denervated forelimb. Significant differences were found in the time course and severity of this abnormal behavior among the 3 groups. Rats that had undergone spinal nerve lesion (group 2) performed significantly less severe autotomy than rats with dorsal rhizotomy (group 1) or peripheral nerve lesions (group 3). The latency to the onset of autotomy was significantly shorter for group 2 than for groups 1 and 3. Electrophysiological investigation of rats in group 2 revealed neural activity in the dorsal roots. The characteristics of the neural discharge were largely a function of postoperative survival times. The possible role of the various types of nerve lesion in producing chronic pain states is discussed. PMID- 6250116 TI - A non-beta-endorphinergic adenohypophyseal mechanism is essential for an analgetic response to stress. AB - The present paper examines the role of pituitary pools of beta-endorphin in mediating the elevation in nociceptive threshold produced by stress. A 5 min foot shock stress, characterized as activating both central and pituitary systems of beta-endorphin (beta-EP) and eliciting a naloxone-attenuated elevation in tail flick latency in rats, was employed. Both total hypophysectomy and selective ablation of the anterior lobe almost completely abolished stress-induced analgesia (SIA), whereas removal of the neuro-intermediate lobe alone proved ineffective. However, manipulation of the hypothalamus-pituitary-adrenal feedback system by administration of either the corticosteroid, dexamethasone, or the corticosteroid synthesis inhibitor, metyrapone, in neither case affected SIA. None of these surgical or pharmacological manoeuvres affected basal nociceptive threshold (BNT). These data indicate that although the integrity of the adenohypophysis is essential for the manifestation of SIA, an adenohypophyseal mechanism, probably involving neither ACTH nor beta-EP, is essential for the development of the analgesia which accompanies stress. PMID- 6250117 TI - [Immunologic mechanisms of allergic predisposition]. PMID- 6250118 TI - [Endocrine methods of diagnosing sclerocystic ovarian degeneration in girls]. PMID- 6250119 TI - CT and IVU in the diagnosis of Wilms' tumour. A comparative study. AB - CT whole-body scanning has been performed in 20 children in the evaluation on a suspected Wilms' tumour. All the patients had abnormal urographic findings including a "non-functioning" kidney in 6 cases, severe urographic changes in ten cases and minor alterations suggesting a small space-occupying lesion in four patients. - A solid tumour was found in 13 of the patients, eight were renal tumours and five neuroblastomas. The rest of the children had benign lesions as the underlying cause of the abnormal clinical and radiological findings. - CT was superior to IVU in the differentiation between a solid tumour and benign lesions such as cysts and hydronephrosis; the examination gave important supplementary information of the size and extent of the solid nature of tumours and tended to be helpful in the preoperative differentiation between Wilms' tumour and neuroblastoma. PMID- 6250120 TI - Unusual renal angiomyolipoma in tuberous sclerosis. AB - A patient with tuberous sclerosis and a normal intravenous urogram 5 years previously presented with a large and palpable upper pole renal mass. Since patients with tuberous sclerosis have small bilateral hamartomas, a Wilms' tumor was suspected. In retrospect, inhomogenous nephrograms should have alerted the radiologist to the multiplicity of other small lesions. Also, a partially lucent rim should have sustantiated that the lesion was not a Wilms' tumor. PMID- 6250121 TI - Small intestinal epithelial brush border enzymatic changes in suckling mice infected with reovirus type 3. AB - Suckling mice infected with reovirus type 3 were examined for changes in the epithelial brush border of the small intestine. After 3 days of infection with reovirus type 3, no significant changes were found in intestinal morphology or activity of any enzymes tested. After 6 days, villi were shortened and blunted with lymphangiectatic lesions and mild mononuclear infiltration in the lamina propria. In addition, there was a significant decrease in lactase (P < 0.001) and enterokinase activity (P < 0.05). However, there were no significant changes in the activities of alkaline phosphatase. In contrast, maltase (P < 0.001) and leucine aminopeptidase (P < 0.05) activities in the infected mice were significantly increased. These data suggest that brush border enzymes are affected differently by reovirus infection. PMID- 6250122 TI - Regional cerebral Na+K+ ATPase activity following octanoate administration. AB - Sodium octanoate in an 0.2 M solution was administered to rabbits by continuous slow IV infusion over 4 hr. Controls were given identical infusions of normal saline. The animals were then sacrificed, brains were removed, and specific areas were isolated and assayed for Na+K+ ATPase activity. Significant inhibition of regional Na+K+ ATPase activity was detected in cortex, thalamus, hypothalamus, pons, and medulla of rabbits given octanoate when compared to controls. PMID- 6250123 TI - Wilms' tumor in a patient with an incomplete form of Beckwith-Wiedemann syndrome. PMID- 6250124 TI - Etiology of pertussis syndrome. AB - One hundred patients with clinical pertussis were studied to determine the etiology of pertussis syndrome. Forty-two (42%) of the patients had either Bordetella pertussis of Bordetella parapertussis isolated from the nasopharynx. In additional 36 (36%) patients, B pertussis was isolated from the nasopharynx of the associated index case or family contact case. Thus, Bordetella was isolated from 78 (78%) of the patients or from their immediate family group. Of the 22 culture-negative patients residing in culture-negative families, 12 had serologic evidence of Bordetella infection and another was from a family group in which two members were seropositive. Therefore, 91 patients (91%) had bacteriologic or serologic evidence of Bordetella infection themselves or within their families. Viral cultures were obtained on 75 of the patients. Adenoviruses were isolated from 33% of those with positive cultures for B pertussis and from 14% of those with negative cultures. In the group without direct or indirect, bacteriologic or serologic evidence of Bordetella infection, the adenoviral isolation rate (13%) was not significantly different from the adenoviral isolation rate (33%) in patients with a positive bacterial culture. These data do not support a role of adenovirus alone in causing pertussis syndrome. PMID- 6250125 TI - Negative serology for hepatitis A and B viruses in 18 cases of neonatal cholestasis. AB - Serologic evidence of hepatitis A virus (HAV) or hepatitis B virus (HBV) infection was sought in 14 patients with biliary atresia and in four patients with neonatal hepatitis; maternal serum was also analyzed. Specific sensitive radioimmunoassays were used to detect HBV surface antigen (HBsAg) and antibody (anti-HBs); complement fixation was used to detect antibody to HBV core antigen (anti-HBc). Antibody to HAV (anti-HAV) was assayed by radioimmunoassay, as well as by immune adherence hemagglutination. There was no evidence of active or past HBV infection in any infant or mother studied. All three infants with detectable anti-HAV were born to mothers similarly anti-HAV positive; serial testing of sera from two of these infants documented disappearance of detectable anti-HAV by 9 months of age. It is unlikely, therefore, that either HAV or HBV had an etiologic role in neonatal cholestasis in these patients. The role of other (non-A, non-B) hepatitis viruses or nonviral etiologies must be investigated. PMID- 6250126 TI - The content of cyclic nucleotides (3',5'-cGMP and 3',5'-cAMP) in cat skeletal muscle during sympathetic cholinergic vasodilatation. AB - Phosphorylase activity and content of cyclic GMP and AMP were investigated in the gastrocnemius muscle of the cat during the development of cholinergic vasodilatation evoked by stimulation of the hypothalamus. Samples of muscle tissue were taken during an early stage of the vascular effect. One of the hindlimbs was denervated and served as control. With the development of the dilator response the conductance in the bed of the femoral artery increased by 143 +/- 12%, phosphorylase "a" activity reached 76.1 +/- 2.1% of the total phosphorylase activity as compared with 49.2 +/- 1.9% in the control, the content of cGMP increased approximately 2-fold. The content of cAMP remained unchanged. All these effects - the increase in blood flow, phosphorylase activation and the increase in cGMP content - were abolished by atropine. It is suggested that acetylcholine, released by sympathetic endings during hypothalamic stimulation, has the effect of increasing the level of intracellular cGMP and that the vasodilatation is secondary to the metabolic changes. PMID- 6250127 TI - Effects of 5-hydroxytryptamine, dopamine, and acetylcholine on accumulation of cyclic AMP and cyclic GMP in the anterior byssus retractor muscle of Mytilus edulis L. (Mollusca). AB - We investigated in vitro accumulation of adenosine 3',5'-monophosphate (induced by 5-hydroxytryptamine and dopamine) and of guanosine 3',5'-monophosphate (induced by acetylcholine) in the anterior byssus retractor muscle of Mytilus. The response to 5-hydroxytryptamine exceeded that induced by equimolar concentrations of dopamine. 1-methyl lysergic acid, a 5-hydroxytryptamine blocking agent, diminished the 5-hydroxytryptamine-induced increase of cyclic AMP level. This parallels the effect of this amine on the contracted muscle. Acetylcholine, which causes a tonic contraction of the muscle, increased intracellular levels of cyclic GMP in a dose-dependent (max. 45-fold at 10(-4) M ACh) manner. The time course of the rise in cyclic GMP level was rapid and transient (peak concentration of cyclic GMP at 2 min). Mytolon was the most effective of all cholinergic blockers tested. It was concluded that cyclic nucleotides may play a role in the modulatory process of the transmitters. A direct relation to the relaxation-contraction process could not be established. PMID- 6250129 TI - Multicompartment kinetic analysis of the amiloride block of Na+ fluxes in frog skin. PMID- 6250130 TI - [Osteomalacia due to vitamin D deficiency. Part One: mechanisms (author's transl)]. AB - Vitamin D deficiency is in most cases subclinical and can only be detected by blood vitamin assays or biochemical changes in phosphorus and calcium metabolism. Clinical and radiological osteomalacia is much less common. It is due to prolonged and profound hypovitaminaemia, which in turn depends upon a variety of factors, the main one being defective photosynthesis. Low vitamin D dietary intake apparently does not result in osteomalacia unless it is accompanied by insufficient exposure to sun. Malabsorption of cholecalciferol results from steatorrhoea of various origina. Disorders in hepatic 25-hydroxylation are due to drug enzymatic induction and seem to be unrelated to the state of the renal function. Disorders in renal 1,25-hydroxylation may be consecutive to reduced renal tissue, impaired stimulation, or inhibiton or even congenital lack of 1 alpha hydroxylase. PMID- 6250128 TI - Mechanism of action of aldosterone on active sodium transport across toad skin. AB - Epithelium of the abdominal skin of the toad, Bufo marinus, has been studied by microelectrode impalement. Using an electrical equivalent circuit model, effective EMF's and specific conductances of the apical and basolateral membrane could be calculated. The skin was divided into 2 fragments for incubation in the presence, or not, of aldosterone (greater than or equal to 0.1 microM). After incubation overnight, sodium transport by the hormone-treated piece was increased 2.7-fold on average, compared to the untreated control. Concomitantly, conductance of the apical border increased more than 3-fold. Furthermore, mean conductance and electromotive force at the basolateral border increased by 80% and by 10%, respectively. Whether the latter changes merely represent delayed adaptation to increased apical conductance, cannot be settled from the data available. PMID- 6250131 TI - [Giant pheochromocytoma mimicking hepatoma]. PMID- 6250132 TI - [African constipation]. PMID- 6250133 TI - Comparative examinations of 99mTc-DMS preparations obtained by labelling dimercaptosuccinate kits with different formulations. I. Comparison of chemical and biological characteristics of Tc P-5 and TCK-12 kits. AB - The chemical and biological properties of two freeze-dried DMS kits for labelling with 99mTc (Tc P-5, manufactured by Boris Kidric Institute, Vinca, and TCK-12, by CIS, Saclay) were compared. A method for the determination of the radiochemical composition of the injection solution is proposed: ascending Whatman 31 paper chromatography in 50% aqueous methanol. The chromatographic results correspond to the biologic activity of the preparations. The biodynamics of both radiopharmaceuticals were determined at intervals in rats. Maximum renal concentrations were achieved at 3-4 hrs post injection (52% kidney and 3% liver uptake for Tc P-5; 59% kidney and 6-8% liver uptake for TCK-12). The bench-lifes of the injection solutions were compared by determining organ distribution after standing of the solutions for 0, 2 and 4 hrs. The Tc P-5 preparation was more stable, since the renal and hepatic concentrations were nearly constant. On the other hand, the hepatic concentration of TCK-12 was increasing during aging of the solution with a simultaneous decrease in renal concentration. PMID- 6250134 TI - Dietary fibre and disease: when roughage is the fibre of health. PMID- 6250135 TI - Childhood cancer: multimodal therapy. PMID- 6250136 TI - Rous sarcoma regression in seven highly inbred lines of White Leghorns. AB - Response to Rous sarcoma virus (RSV)-induced tumors was studied in Regional Poultry Research Laboratory (RPRL) lines 61, 63, 72, 100, 151, and 15I5 and in Reaseheath line C, all highly inbred White Leghorn stocks. Virus inoculations were made in chickens at 6 weeks of age. Tumors were scored subjectively for size on a regular basis and in some instances a tumor profile index (TPI) was assigned which characterized tumor development over a 10 week period for each chicken (TPI 1 = complete regression in 28 days; TPI 5 = terminal tumor). The frequency of tumor regression, terminal tumors, and metastases and mean TPI was examined. The incidence of tumor regression ranged from 92% in line 61 to 0 % in lines 151 and 15I5. The frequency of terminal tumors varied from 100% in line 151 to 2% in line61, while metastasis in chickens with terminal tumors differed from 92% in line 15I5 to 0% in line 61. Mean TPI ranged from 2.0 in line 61 to 4.6 in line 15I5 and 4.7 in line C. The erythrocyte alloantigen genotype at the B blood group locus, (part of the B complex, MHC) and 11 additional blood group loci were known for each of the lines. The data indicate that genetic differences in tumor regression may be pronounced between inbred lines which share similar, if not identical, B locus erythrocyte alloantigens and that other unknown genes are also involved. PMID- 6250137 TI - Combined therapy of Salmonella infection in chickens by antimicrobial agents followed by cultured cecal bacteria. AB - Week-old chickens infected with Salmonella infantis when one day old were treated with antimicrobial drugs either given alone or followed by peroral inoculation of bacterial culture. The bacteria were derived from the cecal contents of adult chickens. The antimicrobial drugs used were: neomycin, neomycin plus oxytetracycline, neomycin plus polymyxin, and sulfadiazine plus trimethoprim. The combined therapy with oxytetracycline plus neomycin and bacterial culture seemed to be the most effective, although the efficacy varied between the parallel trials. Sulfadiazine plus trimethoprim followed by treatment with the bacterial culture decreased the infection rate. The bacterial culture alone also had a slight anti-salmonella effect. When only antimicrobials were given, salmonellae rapidly reappeared in the intestines when the therapy was stopped. PMID- 6250138 TI - Virus infections of the myocardium. PMID- 6250139 TI - Dietary advice in regard to risk for colon and breast cancer. PMID- 6250140 TI - [Effect of adenosine cyclic monophosphate on insulin secretion in healthy rats and in those with alloxan diabetes]. AB - Studies on rats and dogs demonstrated exogenous cAMP to aid elevation of the blood insulin level in healthy animals and, to a lesser extent, in the animals with a mild course of diabetes mellitus caused by alloxan damage of beta-cells. In case of a severe course of diabetes mellitus exogenous cAMP produced no stimulating action on the insulin secretion. PMID- 6250141 TI - [Sensitivity of neurones of the limbic structure, hypothalamus and cerebral cortex of rabbits to microiontophoretic administration of corticotropin]. AB - Reactions of the neurons of the hypothalamus, septum, amygdala of the hyppocampus, and of the brain cortex of rabbits to microionophoretic application of adrenocorticotropic hormone (ACTH) of the hypophysis, noradrenaline and acetylcholine were investigated. About half of the cells in all the brain areas under study changed the frequency of their discharges during the hormone application. The septal and the hyppocampus neurons mostly responded to ACTH by the excitation reactions, whereas neurons of the medial hypothalamus--by the inhibtion reactions. Comparison of the number of cells responding unidirectionally to the hormone and to each of the mediator agents studied, with the number of neurons responding multidirectionally showed no definite significant differences. PMID- 6250142 TI - [Corticosteriod regulation of Na, K-ATPase and ion transport in diverse zones of rat kidney]. AB - Effect of corticosteroids on the activity of transport Na, K-ATP-ase and on the content of Na and potassium ions in various zones of the kidneys in rats with removed adrenal glands was studied. Adrenalectomy diminished the activity of Na, K-ATP-ase and Na level considerably; the greatest changes were observed in the medullary and the papillary zones of the kidneys. Aldosterone administration increased the Na content in the medullary and papillary zones, but failed to influence the enzymatic activity. DOCA injections caused an increase in the enzymatic activity and normalized the Na content in the medullary and papillary zones of the kidneys. Hydrocortisone therapy restored the Na, K-ATP-ase activity in the cortical and the medullary zones. On the basis of the data obtained a conclusion was drawn that both minerals and glucocorticoids took part in the regulation of the transport processes through the membranes of the renal tubules, but influenced different areas of the nephron. PMID- 6250143 TI - [Indirect isotope lymphography in pulmonary tuberculosis]. PMID- 6250144 TI - Angiotensin-1-converting enzyme activity in the spontaneously hypertensive rat. PMID- 6250145 TI - Duodenal lesions associated with adenovirus infection in athymic "nude" mice. PMID- 6250146 TI - Effects of naloxone upon prolactin and costisol in normal women. PMID- 6250147 TI - Effects of adenine guanine and inosine nucleotides on procaine induced nerve blockade in vivo. PMID- 6250148 TI - Effects of the anticonvulsant dipropylacetate on bullfrog sympathetic ganglia. PMID- 6250149 TI - Intracellular changes in arrhythmogenesis and the effect of propranolol. PMID- 6250150 TI - Responses of working rat and guinea pig hearts to carbachol. PMID- 6250151 TI - Effects of 4-aminopyridine on depolarization induced automaticity in ventricular myocardium. PMID- 6250152 TI - Effect of antiarrhythmics on clonidine binding to alpha receptors. PMID- 6250153 TI - Localization of the central cardiovascular action of dibutyryl cyclic AMP. PMID- 6250154 TI - Photoaffinity labelling of angiotensin receptors in the rat portal vein. PMID- 6250155 TI - Production and characterization of monoclonal antibodies to type II regulatory subunit of cyclic AMP dependent protein kinase. PMID- 6250156 TI - Characterization of a plasma membrane enriched fraction of human skin fibroblasts derived from cystic fibrosis patients and age matched controls. PMID- 6250157 TI - Spin label study of phenothiazine interactions with the lipid phase of erythrocyte membranes. PMID- 6250158 TI - Effects of halothane on the neuronal output, membrane properties and synaptic transmission of an isolated neuron. PMID- 6250159 TI - Ethanol, neuroreceptors and postsynaptic membrane function. PMID- 6250160 TI - Molecular mechanisms of beta-adrenergic receptor desensitization. PMID- 6250161 TI - Beta-receptor desensitization in smooth muscle: past, present and future. PMID- 6250162 TI - The contamination of the food chain in Michigan with PBB: the breast-feeding question. PMID- 6250163 TI - Adenine derivatives in epilepsy. PMID- 6250164 TI - Cholera toxin induced epileptogenic focus: an animal model for studying roles of cyclic AMP in the establishment of epilepsy. PMID- 6250166 TI - Iatrogenic neurological diseases of the peripheral nervous system. PMID- 6250165 TI - Vitamin deficiencies. PMID- 6250167 TI - The spacing of rhesus monkey troops changes when a few group members receive delta 9THC or D-amphetamine. AB - Free ranging troops of 18--25 rhesus macaques were housed in large enclosures where a few higher-ranking monkeys were given psychotropic agents (delta 9THC: 4 mg/kg or d-amphetamine: 2 mg/kg). Measures of group spacing were (1) mean distance between all animals. (2) daily variance in mean distance, (3) nearest neighbor distance, (4) daily variance in nearest neighbor distance, (5) index of clumping (S2/mean ratio), (6) % touching, and (7) % movement/2 sec. When 3--4 animals were drugged, the entire group moved closer together and distances were more variable. Acute changes after the first week of delta 9THC and effects after delta 9THC withdrawal were seen in two experiments. Chronic behavioral changes were found for d-amphetamine and in one delta 9THC experiment. PMID- 6250168 TI - Multiple symmetric lipomatosis. A defect in adrenergic stimulated lipolysis II. PMID- 6250169 TI - Estradiol-induced stimulation of 25-hydroxyvitamin D3-1-hydroxylase in vitamin D deficient Japanese quail. AB - The dose-response relationship of estradiol benzoate (E2B)-induced increase of in vitro 1,25-dihydroxyvitamin D3 - 1,25-(OH)2D3 - production in Japanese quail raised on a vitamin D-deficient diet was investigated. 4-week-old male and female Japanese quail, initially raised on a normal calcium and vitamin D diet, were placed on a vitamin D-deficient diet for an additional 4 weeks. At 8 weeks of age, E2B was injected intramuscularly at three different doses (0.03, 0.3 and 3.0 mg/kg) daily for 5 days. Two control groups received an equal volume of vehicle only (0.5 ml/kg, 95% ethanol). Kidney homogenates were incubated with tritiated 25-hydroxyvitamin D3 (25-OH-D3). All three doses of E2B stimulated 1,25-(OH)2D3 production beyond the basal level in both sexes but to a much greater extent in the female. Maximal stimulation was observed with the lowest dose (0.03 mg/kg) of E2B. There was no detectable 24,25-dihydroxyvitamin D3 production in any group. A rise in plasma calcium and phosphorus was seen at all three dose levels of E2B in both sexes. The femur dry weight increased significantly only at the two higher doses of E2B in both sexes. It is concluded that E2B injection in vitamin D deficient Japanese quail can stimulate 25-OH-D3-l-hydroxylase activity beyond the already stimulated basal. PMID- 6250170 TI - Central effect of dibutyryl cyclic AMP on the temperature in the conscious rabbit. AB - In the rabbit, intracerebroventricular administration of dibutyryl cyclic AMP (DBC) produces fever which is selectively antagonised by phenoxybenzamine. This indicates the involvement of central alpha-adrenoceptors in DBC-induced fever. The decrease in DBC hyperthermia after 6-hydroxydopamine (6-OH-DA) supports the viewpoint that DBC-induced fever is dependent on the presence of noradrenaline (NA) in the central nervous system. The accentuation of NA hyperthermia by theophylline suggests that NA fever may be mediated by cAMP. It is unlikely that DBC-induced hyperthermia in the rabbit is mediated via prostaglandins since indomethacin does not inhibit this response to DBC. PMID- 6250171 TI - The binding of 3H-ouabain to Na+-K+ ATPase sites in arterial smooth muscle. PMID- 6250172 TI - Effect of cannabinoids on estrous cycle, ovulation and reproductive capacity of female A/J mice. AB - Virgin A/J female mice were intubated daily for 8 days (short term) or 70 days (long term) with 0, 1, 5, or 25 mg/kg delta 9-tetrahydrocannabinol (delta 9-THC) or 0, 3, 15, or 75 mg/kg crude marihuana extract (CME) in a sesame oil:polysorbate 80:saline vehicle. These dosages approximate light, moderate, and heavy human usage. Short-term exposure to CME has no significant effect on PMS HCG-induced ovulation but appears to: (1) delay entry into proestrus at all dose levels; (2) depress serum progesterone during the luteal phase at the highest CME level used (75 mg/kg), and (3) inhibit female receptivity to males at least at the highest dosage. Long-term oral administration of CME or delta 9-thc had no significant effect on length of estrous cycles or mating (plug formation) but term pregnancies were reduced by 32 and 68% for medium and high dosages, respectively. After a 30-day recovery period, 80% of those females that failed to have successful pregnancies now became pregnant. PMID- 6250173 TI - The influence of a high-bran diet on trace element retention in primates. AB - Proton-induced x-ray emission (PIXE) has become an established analytical method for the determination of trace elements in biomedical samples. The standard PIXE technique has been modified, resulting in a considerable improvement in detection limits. Refinements include the use of an external proton beam, the incorporation of a triggered beam-pulsing system, and the backward angle location (135 degrees to the incident ions) of the Si(Li) x-ray detector. The technique is now clearly capable of rapid, multielemental investigations, and requires a minimum of target preparation. Samples of liver and oesophagus tissue were obtained from 26 baboons at autopsy. Of these, 13 had been maintained on a semi-synthetic (high-bran) diet, with the remaining 13 forming the control group. Some 15 elements were analysed quantitatively; optimum detection limits were in the range 10-20 PPB (1 billion = 10(9). Clear differences were obtained: the high-bran diet is shown to produce imbalances in biologically active elements such as S, K, Ca, Ni Cu and Zn. These results are discussed on the basis of the phytate hypothesis, in terms of which trace elements in the diet are rendered physiologically unavailable to the subject. PMID- 6250174 TI - Physical measurements with a high-energy proton beam using liquid and solid tissue substitutes. AB - The measurement of the physical parameters of a high-energy proton beam, using a range of liquid and solid tissue substitutes, is described. The system, the detectors used and the experimental verification of the tissue equivalence of the new tissue substitutes is presented. The measurements with the scattered but uncollimated proton beam in muscle- and brain-equivalent liquids and in water are compared to similar data obtained from the scattered but collimated beam. The effect of lung, fat and bone on the dose distributions in composite phantoms is also investigated and the necessary corrections established. A simulated patient treatment indicated that the Bragg peak can be positioned with an error not exceeding +/- 0.5 mm. PMID- 6250175 TI - The influence of 3-aminopropansulphonic acid (3-APS) on thalamic neurons. AB - The possible pathways conducting pain are still being discussed. One of the possible pathways may pass through the centrum medianum (CM). In the present study the activity of neurones of CM in cats was recorded using glass micropipettes. 3-aminopropansulphonic acid (3-APS), which is a GABA analogue was administered intravenously in a dose of 0.1, 0.2, 0.5 and 1.0 mmol/kg. The depressive effect starts at the dose of 0.2 mmol/kg. The duration of the effect depends on the dose of 3-APS. Hence 3-APS has a very strong effect on other thalamic neurones so that it may be used for influencing their activity. PMID- 6250176 TI - Review: prostaglandins and cancer. AB - This paper reviews work on the role of prostaglandins in cancer. A substantial body of evidence demonstrates elevated amounts of E series of prostaglandins in human and experimental tumors. Blockade of prostaglandin synthesis in vitro or in vivo results in inhibition of tumor growth. Involvement of prostaglandins is implicated in the actions of tumor promoters like phorbol and polycyclic aromatic hydrocarbon carcinogens. Symptoms like hypercalcemia, osteolysis and tumor metastasis are discussed where disordered synthesis and/or action of prostaglandins and related substances might have a role in the altered metabolism associated with neoplasia. PMID- 6250177 TI - [A cliniconeurophathological study of the "Lewy body disease"]. PMID- 6250178 TI - Effects of morphine and naloxone on the responsiveness (unit and field potential) of three opiate-relevant brain areas during electrical stimulation of the substantia nigra. PMID- 6250179 TI - Stimulation of the plasma membrane enzyme, 5'-nucleotidase, by ethanol exposure to neural cells in culture. PMID- 6250180 TI - Plasma cyclic AMP in schizophrenics. PMID- 6250181 TI - Influence of drug associations incorporating psychotropic drugs and theophylline on cerebral cyclic AMP in mice. PMID- 6250183 TI - Antidepressant drugs: effect on adrenergic responsiveness and monoamine receptors. PMID- 6250182 TI - Peptides, opiate receptors, and cerebroside sulfate: an hypothesis. PMID- 6250184 TI - Peripheral alpha-adrenergic receptor subtypes. PMID- 6250185 TI - alpha-Adrenergic receptor function in schizophrenia. PMID- 6250186 TI - Diethyldithiocarbamate, a superoxide dismutase inhibitor, decreases the radioresistance of Chinese hamster cells. PMID- 6250187 TI - Mechanisms of poliovirus inactivation by the direct and indirect effects of ionizing radiation. PMID- 6250188 TI - [Evaluation of the radioprotective effectiveness of certain aminoalkylthiophosphoric derivatives. 3. Study of the radioprotective effectiveness of S-[S-thioethyl-2-amino-N-(3-aminopropyl)] thiophosphoric acid]. PMID- 6250190 TI - [Ultrasound examination of the breast. Experience with a high resolution 'real time'-scanner (author's transl)]. AB - A new high resolution real-time ultrasound scanner for diagnosis of the breast is presented. The scanner is designed for the examination of peripheral blood vessels, all superficial soft-tissue organs, such as the thyroid, breast, salivary glands, testes as for well as pediatric examinations. It is a mechanical linear scanner with electronic and mechanical transducer focusing. Its high resolution as such and also the sonographic appearance of benign and malignant breast lesions are demonstrated, general problems of ultrasound examinations of the breast are discussed. The equipment under evaluation is of considerable value in the differentiation of palpable or otherwise localised breast tumors. It is less useful for a general application in the screening for breast cancer. PMID- 6250189 TI - [Possibility of modifying the distribution of 35S-APAETP, administered orally, by using other radioprotective agents]. PMID- 6250191 TI - [Do radiographic findings in mammography of a malignant mammary gland tumor permit conclusions about its histology? (author's transl)]. AB - Histo-pathological classification of malignant breast tumors is compared with their morphological radiology. Shape, density and kind of growth of a tumor are not always in accordance and conclusion with its histological picture. PMID- 6250192 TI - [The role of mammography in the diagnosis of cystosarcoma phylloides (author's transl)]. AB - Cystosarcoma phylloides is not a single disease entity, but, a spectrum, which includes a benign, a non-metastatic malignant and a metastatic malignant form. Neither macroscopic nor microscopic examinations enable one to prediction as to whether the tumor is of a potentially metastatic kind or not. Neither pain nor infiltration or ulceration of the skin are reliable signs of malignancy; palpable axillary lymphnodes are misleading too. The treatment is composed of either a wide local excision of the tumor or a simple mastectomy. In cases where the lymphnodes have increased in size, simple mastectomy plus axillary lymphnodes dissection will be done. Since most tumor recurrence occurs following a local excision of the tumor only simple mastectomy is the surgical method of choid. The author presented two cases, examined by mammography; one case of malignant cystosarcoma phylloides malignum and one case of carcinoma. Both were similar in their clinical and radiographic presentation. Both cases demonstrate the difficulty of radiographie and pathologic diagnosis. A warning is given to radiologists not to compete with the pathologists for the histologic diagnosis but to limit themselves to suggest the presence of a possibly malignant tumor and the need for surgery. PMID- 6250193 TI - [Ultrasonography of the kidney (author's transl)]. AB - Ultrasound is a nowadays widely accepted diagnostic tool in urology and nephrology. It can improve, supplement or even replace standard radiographic procedures. Indications and limitations are presented. Main indications for renal ultrasound are renal and pararenal masses and nonvisualisation of the kidney. As in any other imaging procedure, the diagnostic accuracy depends on the following: location and size of the lesion and its density compared to that of the neighborhood, and the quality of the imaging unit and of the investigator. PMID- 6250194 TI - [Renal embolisation, renal cystography and percutaneous nephrostomy (author's transl)]. AB - In renal disease, therapeutic procedures performed by radiologists include embolisation, cystography with obliteration and percutaneous nephrostomy. More than 72 therapeutic occlusions of the renal artery by balloon, coil, and gelfoam are presented. Basic differences in technique of application and in the mechanism of Ethibloc in comparison to other kinds of embolisation material are pointed out. In 61 diagnostic punctures of renal cysts, guided by sonograpny, 31 were treated by injection of Lipiodol. As in cystography, the combination of sonography and radiology proved to be highly valuable in 37 percutaneous nephrostomies. Technique, indication, contraindication, and complication of renal embolisation, renal cystography and percutaneous nephrostomy are briefly discussed. PMID- 6250195 TI - Infusion hepatic angiography in the detection of small hepatocellular carcinomas. AB - Selective celiac angiography, conventional hepatic angiography, and infusion hepatic angiography, were utilized for the diagnosis of hepatocellular carcinoma in 90 patients. The first two of these methods were not always able to detect small foci measuring less than 2 cm in diameter, due to vascular proliferation which cannot be distinctly identified by conventional angiography. In these cases infusion hepatic angiography enhanced the detection of the foci. This method is indispensible in the diagnosis of hepatocellular carcinoma. PMID- 6250196 TI - Prolonged injection angiography for diagnosing intracranial neoplasms. AB - Prolonged injection angiography (PIA), in which large amounts of contrast material are administered for three or four seconds, was used to visualize the vasculature of 70 intracranial neoplasms. Tumor stains were demonstrated better with or solely by PIA in all pituitary adenomas with suprasellar extension and in most meningiomas. PIA was less effective in tumors with marked arteriovenous shunts or in low-grade gliomas. PIA is especially indicated when avascular or hypovascular masses are encountered on conventional angiography or when contrast enhancement is encountered on computed tomography (CT). PIA is also indicated to demonstrate neoplasms which are not enhanced with contrast media on CT since PIA demonstrates the venous anatomy surrounding the tumors especially well. PMID- 6250197 TI - Delayed scanning with DMSA: a simple index of relative renal plasma flow. AB - Relative renal uptake of 99mTc-dimercaptosuccinic acid (DMSA) was compared with the relative effective renal plasma flow (ERPF) to each kidney. In 25 patients with serum creatinine less than or equal to 2.0 mg/dl, there was excellent agreement when the regions of interest were assigned by a computer. In 10 patients with serum creatinine greater than 2.0 mg/dl, agreement was poor. A 24 hour image is sufficient to obtain such data. In patients with renal failure, this technique may give inaccurate results due to high tissue background activity; moreover, since it reflects the current functioning status of the kidney, it should not be used to predict recoverable function in patients with acute or unstable renal disease. PMID- 6250198 TI - Radiologic diagnosis of oat cell cancer in a high-risk screened population. AB - A screening program of 10,040 cigarette-smoking men over 45 years of age was undertaken in an attempt to achieve earlier diagnosis, thereby increasing the cure rate, of oat cell lung cancer. Of the 155 men who were found to have lung cancer, 27 (17%) had confirmed oat cell cancer. Only one case was diagnosed at the first examination. The other 26 cases (called incidence cancer) were diagnosed by subsequent examinations. In 24 of the 26 patients, the tumor was not found until it was advanced (Stage III), and of these patients, only one is alive at 21 months follow-up. Two tumors were diagnosed as oat cell carcinoma at an early stage (Stage I), and both patients are alive with no evidence of disease at seven and 24 months. The screening program used in this study did not succeed in detecting oat cell cancer at an early stage. PMID- 6250199 TI - Postinflammatory pseudotumors of the lung: fibrous histiocytoma and related lesions. AB - Three cases of pulmonary fibrous histiocytoma, sometimes known as xanthogranuloma and fibrous xanthoma, are described. The lesion is part of a spectrum of diseases known as postinflammatory pseudotumors of the lung. It is usually discovered on routine radiographic examination on which it appears as a well circumscribed mass, and it usually has a benign course. The microscopic findings upon which diagnosis is based, the theories of origin, and previously reported cases are discussed. PMID- 6250200 TI - Pitfalls in mammography: demonstrating deep lesions. AB - The difficulty of demonstrating lesions near the chest wall is one source of error in mammography. A mediolateral xeroradiograph of the breast which images the chest wall was added to the routine mediolateral and cephalocaudal film screen projections to minimize this problem. In one case, a posterior breast lesion was detected solely on the xeroradiograph. However, three tumors were demonstrated on the film-screen mediolateral view but not on the chest wall xeroradiographic view. Using the two mediolateral views results in increased detection of malignancies in the posterior mammary tissues. PMID- 6250201 TI - Radionuclide imaging of lipoma and liposarcoma. AB - Radionuclide imaging with technetium-99m phosphate compounds was performed in 18 patients with deep-seated soft-tissue masses. The histologically established diagnosis was intra- or intermuscular lipoma in 13 patients and liposarcoma in five. Radionuclide scans demonstrated disparate scintigraphic characteristics in these two often clinically similar lesions. Soft-tissue radionuclide accumulation occurred in two lipomas and corresponded to radiographically evident calcification. All liposarcomas were uncalcified and demonstrated intense radionuclide activity. This activity may be related to the angiographic and histologic hypervascularity of liposarcomas, which is also demonstrable on computed tomography as contrast enhancement; hence, these modalities offer the same nonspecific diagnostic information. It is concluded, however, that plain radiography and radionuclide scaning should suffice to establish the diagnosis of lipoma. PMID- 6250202 TI - [Studies on microbial lipoxygenase (author's transl)]. PMID- 6250203 TI - Evidence against prostaglandin modulation of cardioaccelerator nerve activity in the anesthetized dog. AB - The hypothesis that prostaglandins have a modulatory role in adrenergic neurotransmitter release was tested in the anesthetized dog. Inhibition of prostaglandin synthesis with indomethacin (10 mg/kg, i.v.) did not alter positive chronotropic responses to cardioaccelerator nerve stimulation or blood pressure responses to exogenous norepinephrine. In the presence of indomethacin, infusions of PGE, (0.01 and 0.1 microgram kg-1 min-1) also failed to influence the responses to cardioaccelerator nerve stimulation although the blood pressure responses to exogenous norepinephrine were reduced in a dose-related manner. It was concluded that endogenous prostaglandins and exogenous PGE2, the purported physiological inhibitor of neurotransmitter release in cardiac tissue, do not play a role in modulating chronotropic responses during cardioaccelerator nerve stimulation in the anesthetized dog. PMID- 6250204 TI - [Study of blood serum ACTH and urinary 17-hydroxycorticosteroids in psoriasis treated with different steroid ointments]. PMID- 6250205 TI - Restoring effects of refeeding and dibutyril cyclic AMP on the increased glucagon secretion of rat pancreatic islets during starvation. AB - The glucagon release in the presence of glucose and the interaction of dibutyril cyclic AMP was studied in isolated pancreatic islets from fed and 96 h-fasted rats incubated for 30 min. In both states the increase of glucose concentration produced a similar inhibition of glucagon release and stimulation of cyclic AMP content. Higher glucagon secretion and lower cyclic AMP contents were observed in islets from fasted than in those from fed animals at both 2.75 and 16.7 mM glucose. Islets from rats starved for 96 h and refed for 48 h with normal diet or oral 20% glucose showed glucagon release patterns similar to those of controls. Addition of 2 mM dibutyril cyclic AMP to the incubation medium inhibited the fasting-induced increase of glucagon secretion at both glucose levels. These results show an inverse correlation between glucagon secretion and islet cyclic AMP content. However, the sensitivity of the islet to glucose-induced inhibition of glucagon secretion appears to be independent of the islet cyclic AMP levels. PMID- 6250206 TI - Tissue immunoreactive prolactin hormone in breast cancer. AB - The prolactin contents of the cytosol extracts of 159 human mammary carcinomas was measured by specific radioimmunoassay. Of these extracts 157 contained measurable prolactin (detection limit, 7.8 ng/g tumor). The levels measured were in most cases greater than would be expected to be due to only serum contamination. The levels of prolactin did not correlate with either estrogen or progesterone receptor content of the tumors, or menopausal status of the patient. PMID- 6250207 TI - Changes in brain N-demethylation and opiate receptor content correlate with analgesic effectiveness of morphine. AB - Castration of male rats results in an increase in the analgesic effectiveness of morphine. This change is abolished by testosterone replacement. The greater effectiveness of morphine in the castrated rats is not due to differences in liver metabolism but correlates with increases in brain N-demethylation and opiate receptor content. PMID- 6250208 TI - Dopamine-beta-hydroxylase: a modulator of beta adrenergic receptor activity. AB - The demonstrated proportionality between norepinephrine and dopamine-beta hydroxylase released exocytotically from sympathetic nerve endings led us to explore the possible physiologic significance attached to this proportionality. The beta adrenoreceptor mediated desensitization of the hyperpolarization response to norepinephrine observed in pinealocyte membranes was rapidly reversed following the infusion of dopamine-beta-hydroxylase (DBH). This infusion also resulted in an augmented cyclic 3',5'-adenosine monophosphate (cAMP) response to isoproterenol in vitro. We suggest that the dissociation of the concentrations of norepinephrine and dopamine-beta-hydroxylase released into the synaptic cleft as a result of continuous sympathetic nerve stimulation produces a relative dopamine beta-hydroxylase deficiency which is associated with the beta receptor desensitization. The observation that DBH restored the membrane sensitivity to NE in vitro in rat pineals, suggests that it either augments the rate at which agonist recognizes the beta receptor and couples to adenylate cyclase, or directly increases the activity of adenylate cyclase itself. The increase in cAMP generated in the presence of DBH supports such a hypothesis. PMID- 6250209 TI - [Pancreatic cancer associated with pancreatitis and pseudocysts]. AB - A discussion is presented of the diagnostic problems encountered in 27 of 153 consecutive cases of pancreatic cancer, all of which were initially misinterpreted as acute (relapsing) or chronic pancreatitis or pancreatic pseudocysts. PMID- 6250210 TI - [Chemical structure and biological activity of cholecystokizin octapeptides with respect to the stomach and pancreas]. AB - Dose response curves of the octapeptide of cholecystokinin (CCK-8) and 3 of its methoxinine analogues have been established in 4 conscious dogs with respect to gastric and pancreatic secretion. In the analogues the methionine was replaced by methoxinine in position 3 (B) and (D) or 6 (C). Of the 4 tested substances CCK-8 exhibited most activity with regard to pancreatic protein secretion, followed by B, C, and D. Analogue C had the strongest stimulating effect on gastric acid secretion, while its effect on pancreatic secretion was minor. Correlation of chemical structure with biological activity points to the importance of the methionine residue in position 6. PMID- 6250212 TI - The development of oocytes and ovarian follicles of mammals. PMID- 6250211 TI - [Co-occurring liver cell adenoma and focal nodular hyperplasia due to contraceptives. Case report]. AB - The case is presented of a female patient who developed two pill-associated tumors in the liver, a liver cell adenoma in the right lobe and focal nodular hyperplasia in the left lobe. The pathological, clinical and prognostic features are discussed. PMID- 6250213 TI - Analysis of the irreversible process of proton transport in the purple membrane of Halobacterium halobium. AB - The proton transport across biological membrane, accompanied by energy transformation, is closely related with many basic processes involved in the maintenance of life. Active researches are carried out in this field, but so far we have not known a complete calculation. This paper presents a model of an open and closed photon-controlled ion pore with a quantitative analysis of the irreversible process of the proton transport across the purple membrane. Upon absorbing photon by the purple membrane, the deprotonation of the Schiff base causes the ion pore to open, but it will close when it returns to bR570. A set of nonlinear differential equations describing this model is given. The stability of the equations is discussed. The results of the numerical calculation for steady state are found in good agreement with the experimental data of Bakker. PMID- 6250214 TI - Teratocarcinomas and mammalian embryogenesis. AB - In the last decade there has emerged an appreciation of the remarkable similarity between the cells that give rise to teratocarcinomas in mice and the cells that give rise to the developing mouse embryo. The resemblance is so close that in certain instances the tumor stem cells can join with their embryonic counterparts and develop into a completely normal mouse. The availability of stem cell lines isolated from mouse teratocarcinomas has made possible a number of new biochemical, immunological, and genetic approahes to the study of early mammalian development. PMID- 6250215 TI - Thyroid hormone receptor-containing fragment released from chromatin by deoxyribonuclease I and micrococcal nuclease. AB - Limited deoxyribonuclease I and micrococcal nuclease digestion of hepatic nuclei from euthyroid rats injected with 125I-labeled triiodothyronine ([125I]T3) releases a discrete [125I]T3-labeled chromatin fragment (5.8S) which is larger than the T3 receptor (3.5S). These results suggest the T3 receptor is associated with a restricted fraction of hepatic chromatin that has a nuclease sensitivity characteristic of transcriptionally active chromatin. PMID- 6250216 TI - Vitamin D deficiency inhibits pancreatic secretion of insulin. AB - The effects of a vitamin D deficiency on insulin and glucagon release was determined in the isolated perfused rat pancreas by radioimmunoassay of the secreted proteins. During a 30-minute period of perfusion with glucose and arginine, pancreases from vitamin D-deficient rats exhibited a 48 percent reduction in insulin secretion compared to that for pancreases from vitamin D deficient rats that had been replenished with vitamin D. Vitamin D status had no effect on pancreatic glucagon secretion. This result, along with the previously demonstrated presence in the pancreas of a vitamin D-dependent calcium-binding protein and cytosol receptor for the hormonal form of vitamin D, 1,25 dihydroxyvitamin D3, indicates an important role for vitamin D in the endocrine functioning of the pancreas. PMID- 6250217 TI - Dexamethasone fails to suppress beta-endorphin plasma concentrations in humans and rhesus monkeys. AB - In humans and rhesus monkeys, dexamethasone decreased concentrations of plasma cortisol but did not alter circulating beta-endorphin immunoreactivity. Contrary to current theory suggesting that pituitary beta-endorphin and adrenocorticotropic hormone are controlled by identical regulatory mechanisms for synthesis and release, our evidence suggests that in higher primates the established glucocorticoid feedback mechanism for the adrenocorticotropic hormone cortisol system does not regulate beta-endorphin secretion in the same way. PMID- 6250218 TI - Pituitary gonadotropin-releasing hormone receptors during the rat estrous cycle. AB - The binding of [6-alanine]gonadotropin-releasing hormone to pituitary plasma membranes increased threefold between metestrus and early proestrus in female rats. Receptor numbers fell rapidly on the afternoon of proestrus coincident with the preovulatory gonadotropin surge. The numbers of receptors for gonadotropin releasing hormone were positively correlated with concentrations of estradiol in serum; this pattern may be a necessary component of increased pituitary sensitivty to gonadotropin-releasing hormone observed during proestrus. PMID- 6250220 TI - Electrical stimulation of the midbrain mediates metastatic tumor growth. AB - Pulmonary metastases were counted 10 days after female rats received tail-vein injections of Walker-256 carcinosarcoma cells. Previous observations that halothane anesthesia plus hind-limb amputation increases the number of metastases were confirmed. Amputation under the analgesia of electrical stimulation of the midbrain was found to increase metastatic activity. However, the stimulus produced analgesia alone also increased the number of metastases. Systemically administered naloxone blocked the analgesic effect of midbrain stimulation but did not block the increase in the number of pulmonary metastases. PMID- 6250219 TI - J genes for heavy chain immunoglobulins of mouse. AB - A 15,8-kilobase pair fragment of BALB/c mouse liver DNA, cloned in the Charon 4A lambda phage vector system, was shown to contain the mu heavy chain constant region (CHmu) gene for the mouse immunoglobulin M. In addition, this fragment of DNA contains at least two J genes, used to code for the carboxyl terminal portion of heavy chain variable regions. These genes are located in genomic DNA about eight kilobase pairs to the 5' side of the CHmu gene. The complete nucleotide sequence of a 1120-base pair stretch of DNA that includes the two J genes has been determined. PMID- 6250221 TI - 1 alpha, 25-Dihydroxyvitamin D3 nuclear receptors in pituitary. AB - Specific binding of 1 alpha,25-dihydroxyvitamin D(3) was found in nuclear and cytosol fractions of the bovine pituitary. For nuclear binding. the dissociation constant was 0.1 namomole per liter, and maximum binding was 104 femtomoles per milligram of protein. In competition studies, 25-hydroxyvitamin D(3) was 300 times weaker than 1 alpha,25-dihydroxyvitamin D(3). The existence of high affinity sites supports a physiologic role for 1 alpha,25-dihydroxyvitamin D(3) in the pituitary. PMID- 6250222 TI - Stress-induced eating is mediated through endogenous opiates. AB - The interaction of endogenous opiates and stress-induced eating in rats was evaluated by pharmacological manipulation. Eating induced by the tail-pinch method was inhibited by the opitate antagonist naloxone; after being repeatedly stressed over a 10-day period and then given nalozone, the rats behaved in a manner indistinguishable from the "wet-dog" shakes of opiate withdrawal. Thus endogenous opiates may have a role in the control of stress-related eating, a finding that may have therapeutic implications for humans. PMID- 6250223 TI - Multidisciplinary approach to the diagnosis of hepatoblastoma: ultrasound, nuclear medicine, and angiography. AB - This report demonstrates the findings of angiographic, nuclear medicine, and ultrasonic examinations in a case of primary liver neoplasm (hepatoblastoma). The use of a multidisciplinary approach pin-pointed the neoplasm and guided a liver biopsy for subsequent tissue diagnosis. The patient is now undergoing radiation therapy, with monitoring by serial ultrasonic examinations. PMID- 6250224 TI - Oat cell carcinoma presenting as a pseudoaneurysm. AB - A man thought to have a dissecting aortic aneurysm was found to have an oat cell carcinoma encasing the thoracic aorta and great vessels. This is the first reported association of pseudoaneurysm with an oat cell carcinoma and is only the third case of a tumor presenting as a pseudoaneurysm. False-positive or false negative results of aortography, echocardiography, and thoracic CT scanning point out the shortcomings of modern, sophisticated laboratory and radiographic procedures. PMID- 6250225 TI - Prevalence of genital herpesvirus infection in Thai women. AB - Specimens from uterine cervices were collected from 157 women patients from a Venereal Disease Clinic for isolation of Herpesvirus hominis type 2. None of these women had detectable herpetic lesions. Virus was isolated from 14 cases, 6 of whom also had gonorrhoea. These results indicated that a large number of women are shedding the virus asymptomatically. The sera from these patients as well as sera from 101 healthy controls were subjected to serological tests for herpesvirus antibody using the indirect haemagglutination (IHA) test and the enzyme linked immunosorbent assay (ELISA). It was found that both IHA titer and ELISA value of the sera from the patients were significantly higher than those of the control sera. Positive correlation between IHA and ELISA value was also found. Likewise was the demonstration of positive correlation between the positive virus isolation and the positive serological tests. PMID- 6250226 TI - An outbreak of acute conjunctivitis caused by coxsackievirus A24 in Kuala-Lumpur, Malaysia, 1978. AB - An investigation of an outbreak of acute conjunctivitis in Kuala Lumpur from May to August 1978 was made. A total of 2,133 cases was involved, most of whom were adult Malay males of low income status from the surrounding villages and low-cost flats. The majority of cases had bilateral conjunctivitis with clear discharge. Pain and subconjunctival haemorrhage were not common and recovery, mostly without complications, occurred within 1 week. Eye scrapings and paired sera specimens were examined and the causal agent was found to be Coxsackievirus A24 (CA24). PMID- 6250227 TI - Cell-mediated immune response in amebiasis. AB - Studies on cell-mediated immune response (CMIR) to amebia antigen in amebic liver abscess showed conflicting results. The leucocyte migration test was employed in nine cases of amebic liver abscess and CMIR to amebic antigen was demonstrated in four cases. The role of CMIR in the pathogenesis of amebic liver abscess remains unknown but its presence is confirmed. PMID- 6250228 TI - [Clostridium sepsis as a result of acute gangrenous cholecystitis]. PMID- 6250229 TI - The Epstein-Barr virus. PMID- 6250230 TI - The importance of early ultrasonography in jaundice. AB - The ultrasonographic findings in 3 patients with longstanding jaundice of clinically unsuspected obstructive nature are presented and discussed. Attention is drawn to the importance of early ultrasonography, even when the clinical and biochemical picture is not necessarily in keeping with a diagnosis of obstructive jaundice. PMID- 6250231 TI - A cannabis dilemma. PMID- 6250232 TI - Carcinoma of the breast in children: a case report and review of the literature. AB - The case of a 10-year-old girl with juvenile carcinoma of the breast is presented. The literature is reviewed and current thoughts relating to the treatment of breast carcinoma in children are discussed. The major controversy seems to revolve around the choice between radical and local excision in cases of juvenile or secretory breast cancer. PMID- 6250233 TI - Urinary virus excretion in pregnancy. AB - In a series of 774 women with pregnancies ranging from 7 weeks to term, virus particles representing five different groups have been detected in urine specimens by negative staining electron microscopy. Of the virus-positive women, 0,39% excreted papillomavirus (in the absence of genital warts), 3,1% polyomavirus, 0,26% adenovirus type II, 0,65% an antibody-coated unidentified virus particle and 7,7% a membrane-associated virus-like particle. The implications of these findings are discussed in the light of the apparently increased susceptibility of pregnant women to virus infection. PMID- 6250234 TI - Choriocarcinoma and invasive mole. PMID- 6250235 TI - Fibrosarcoma of the breast. AB - A total of 5 583 symptomatic patients were referred for xeromammography at the Mammographic Clinic, Johannesburg General Hospital, between June 1974 and January 1979. Four hundred and fifty-eight carcinomas and 3 sarcomas were recorded. The incidence of carcinoma in our series was 7,9% and that of sarcoma 0,65%, while there was a 0,21% incidence of pure fibrosarcoma. Comparison is made with world literature. PMID- 6250236 TI - Change in the prevalence of active pulmonary tuberculosis discovered at autopsy in black miners. AB - The prevalence of active pulmonary tuberculosis at autopsy in two groups of Black miners who had died while working on the mines during the periods 1961-1963 and 1974-1978 was investigated. Radiographs had been taken regularly in both groups while they were alive to detect early tuberculous lesions. If any such lesions were found, the worker was excluded from the populations which were being studied. A highly significant secular decrease in the prevalence of active pulmonary tuberculosis was found. Possible explanations for this finding are discussed and it is concluded that there may be a decline in the incidence of tuberculosis in Blacks. PMID- 6250237 TI - Cimetidine in the treatment of herpesvirus infections. AB - In August 1977 a patient developed herpes zoster just before she commenced a course of cimetidine (Tagamet; Smith, Kline & French) for a chronic gastric ulcer. She experienced both rapid relief of the ulcer symptoms and, rather unexpectedly, dramatic relief of the herpetic pain and rapid disappearance of the eruption. On the basis of this observation cimetidine was prescribed to 21 patients with herpes zoster. The results continued to be encouraging in all but 3 patients. The trial was therefore extended to other herpesvirus infections. In all but 1 of 7 patients with herpes labialis the blisters were aborted, and in 1 patient with herpes keratitis the result was also encouraging, the attacks being markedly shortened in duration and reduced in frequency. The results of this preliminary trial warrant a systematic scientific inquiry into the potential role of cimetidine in the treatment of hypesvirus infection, as well as a study of the mechanisms involved. PMID- 6250238 TI - Metamorphosis of chronic granulocytic leukaemia, lytic bone lesions and hypercalcaemia. A case report. AB - Chronic granulocytic leukaemia may undergo metamorphosis characterized by diffuse granulocytic sarcomas resulting in lytic bone lesions and hypercalcaemia. A patient with this rare complication is reported. PMID- 6250239 TI - Griseofulvin and viruses. PMID- 6250240 TI - Adrenalectomy in the treatment of incurable carcinoma of the breast in five hundred consecutive patients. PMID- 6250241 TI - [Viruses and the kidneys]. PMID- 6250243 TI - [Antimicrobial chemotherapy in severe infections. Experience with a new beta lactam antibiotic]. PMID- 6250242 TI - [Prostaglandins and the heart]. PMID- 6250244 TI - Response of cyclic nucleotides to stimulation by prostaglandin E1 and 5 hydroxytryptamine in stored human platelets. PMID- 6250245 TI - Effect of oral delta-9-tetrahydrocannabinol on coagulation. PMID- 6250246 TI - Inhibition of platelet adenylate cyclase by ADP. PMID- 6250247 TI - [Receptors for polypeptide hormones]. PMID- 6250248 TI - [Intracellular mediators for polypeptide hormones]. PMID- 6250249 TI - Differentiative and proliferative effects of (But)2cAMP, n-butyric acid and prednisolone on the malignant melanoma cell line (TM-1) in vitro and in vivo. AB - Both (But)2cAMP and n-butyric acid suppressed the proliferation of TM-1 cells and induced the formation and elongation of the cellular processes in vitro. Prednisolone stimulated the proliferation of TM-1 cells and increased the number of polygonal cells in vitro. These results indicated that (But)2cAMP and n butyric acid induce the differentiation of TM 1 cells, whereas prednisolone brings the cells in an undifferentiated state. The growth of TM-1 cell tumor transplanted into nude mice was suppressed by 5 mg of (But)2cAMP and 1 mg of theophylline. Remarkable histological changes were seen in the tumors treated with these agents as compared with untreated tumors. This suggests that (But)2cAMP suppresses the proliferation of TM-1 cells in vivo. PMID- 6250250 TI - Cerebro-cortical innervation of the urinary bladder. AB - In this report cerebro-cortical innervation of the urinary bladder has been investigated in man by the use of electroencephalography and in the cat by the application of the evoked potential technique. Electroencephalographic monitoring during bladder filling while the patient was asleep was a useful method to determine cerebral response to stimulation of bladder sensory receptors. Bladder filling was performed during stage IV sleep. In the intact individual detrusor reflex contraction or attainment of bladder capacity was followed by prompt arousal and desynchronization of EEg rhythms. In patients with interruption of bladder sensory pathways in the periphery or in the spinal cord there was loss of impairment of the EEG response to bladder filling. In the cat, anesthetized with sodium pentobarbital, electrical stimulation of the nerve supply to the urinary detrusor muscle and to the pudendal nerve innervation to the periurethral striated muscle and anal sphincter, evoked a diphasic response in the cerebral cortex of the frontal lobe. All responses were grouped in the same area and were of short latency. Similar potentials have been evoked in man. These studies demonstrate that the peripheral, spinal and cerebral innervation of the urinary bladder in man are definable by electrophysiologic techniques. As a result, these electrophysiologic techniques are applicable to defining neuropathic changes in the urinary bladder innervation in man. PMID- 6250251 TI - Newly synthesized glycoproteins in plasma membranes of cells transformed by SV40 and its gene A function. AB - SV40 temperature sensitive mutant transformed mouse cells synthesized different membrane glycoproteins at 5 to 10 hr after temperature shift and inhibition of DNA synthesis by cytosine arabinoside (Ara C) after temperature shift led to the alterations in the patterns of newly synthesized membrane glycoproteins analyzed by polyacrylamide gel electrophoresis. PMID- 6250252 TI - The interaction of cadmium and certain other metal ions with proteins and nucleic acids. AB - The toxic effects of cadmium and other selected divalent cations are presumed to be related to specific chemical and physical characteristics of the ion. The chemistry of cadmium and metal ions in general is reviewed from the viewpoint of such relevant properties as ion polarizability, electronic structure, and the hard-soft characteristics. The softness of metal ions is seen as a useful single parameter to correlate with the affinity for nucleic acids and proteins and with toxic effects. The effects of cadmium on nucleic acids and proteins are examined for a number of specific cases to illustrate the variety of interactions that are well recognized and to demonstrate the utility of soft metal ions as reagents and probes for examining the relationship of structure and function in these macromolecules. PMID- 6250253 TI - Induction of xenobiotic metabolism in rats by brominated diphenyl ethers administered for 90 days. AB - The administration of doses as low as 0.78 mu mol/kg/day p.o. for 90 dys of the commercial fire retardants pentabromodiphenyl ehter and octabromodiphenyl ether to rats resulted in increased O-ethyl O-p-nitrophenyl phenylphosphonothioate (EPN) detoxification and p-nitroanisole demethylation. This dose of pentabromodiphenyl ehter and higher doses of octabromodiphenyl ether also increased cytochrome P-450 and NADPH cytochrome c reductase. Measurements made at 30 and 60 days after the last dose showed that these indicators of induced xenobiotic metabolism return to control levels slowly. The results demonstrate that these inducers are not only potent but that their effects may be long lasting. PMID- 6250254 TI - The aging Leydig cell: 1. Testosterone and adenosine 3',5'-monophosphate responses to gonadotropin stimulation in rats. AB - Plasma testosterone levels before and after a single injection of hCG were significantly lower in 24-month old rats than 60--90 day old animals (p less than 0.001). Even with repeated hCG administration for three weeks, plasma testosterone levels of old rats could not be restored to levels present in unstimulated young rats. In response to in vitro LH and 8-bromo-cyclic AMP stimulation, purified young Leydig cells produced significantly higher amounts of testosterone than Leydig cells from old rats. Maximal testosterone formation of the young Leydig cells in response to LH was 42.0 +/- 6.88 ng/10(6) cells, while cells from old rats produced only 16.8 +/- 3.69 ng/10(6) cells (p less than 0.01). However, the dose of LH at which one half maximal response (ED50) occurred was 0.1 mIU/ml for young Leydig cells and 0.05 mIU/ml for old Leydig cells. Basal and 1.0 mIU LH-stimulated cyclic AMP formation were comparable in both groups, but cyclic AMP formation in response to 10 mIU of LH was significantly less in the old rats (p less than 0.05). Present results demonstrate impaired steroidogenic capacity of old rats both in vivo and in vitro. Decreased testosterone response in old rats most likely is the consequence of understimulation of Leydig cells by gonadotropin; however, there appear to be additional intrinsic defects in old Leydig cells. PMID- 6250255 TI - Conjugation of androgens and estrogens by human breast tumors in vitro. AB - The metabolism of 3H-androstenedione (delta 4-A) and 3H-estriol (E3) was studied in 12 human breast tumors. Part of each tumor was analyzed for estrogen receptor content. Aliquots of tumor homogenates were incubated for 2 hr separately with 3H delta 4-A and 3H-E3 in the presence of appropriate cofactors. No distinct differences emerged in the profiles of the unconjugated metabolites of 3H-delta 4 A, the major compounds in the approximate order of descendence being androsterone, androstanedione, testosterone, 5 alpha-androstane-3 alpha, 17 beta diol, epiandrosterone, and dihydrotestosterone. One tumor homogenate from an infiltrating lobular carcinoma converted 3H-delta 4-A to glucosiduronate metabolites (11%), of which androsterone, 6.4%; testosterone, 1.6%; and androstanediol, 0.6% predominated. The homogenate of this tumor and two other tumors converted 3H-E3 to 3H-E3-3S. Conversions of E3 to E3-3S in the other tumor homogenates were less than 0.6%. No correlation between receptor content and the capability of the tumor to conjugate delta 4-A or E3 evolved. However, correlations between steroid hormone metabolism and tumor histopathology may exist. PMID- 6250256 TI - Effects of herpes simplex virus antigens on human mixed lymphocyte culture. PMID- 6250257 TI - [Sodium flux across a muscle fiber membrane in saline media lacking sodium and potassium]. AB - Unidirectional sodium fluxes were measured in frog sartorius muscle with radioisotopes and emission techniques. A comparison was made of sodium rate constants, evaluated from the efflux of sodium preexisting in muscle, and from the efflux of 22Na. The rate constants for sodium influx and efflux were determined in solutions in which sodium and potassium were substituted for magnesium, choline and tris. Ouabain inhibits about 40% of sodium efflux investigated. In sodium- and potassium -free media, the rate constant for sodium efflux does not depend on the internal sodium concentration both for ouabaine resistant and ouabain-sensitive components. The ouabain-sensitive and ouabain resistant sodium fluxes and operation pump in cation deficient medium have been discussed. PMID- 6250258 TI - [The concept of carcinoma in situ]. PMID- 6250260 TI - [Public high schools in psychiatric after care]. PMID- 6250259 TI - [Rapid diagnosis of respiratory virus infections in children. Respiratory syncytial virus demonstrated by the immunofluorescent technic]. PMID- 6250261 TI - [Paget's disease of the nipple]. PMID- 6250262 TI - Integrated imaging for the evaluation of the urologic diseases of childhood. AB - The rational selection of imaging modalities for the diagnosis of renal and adrenal masses in children is discussed with a view toward obtaining an accurate assessment of pathologic changes with the least amount of stress and expense to the patient. The integration of the results of these tests in specific clinical settings is also described. PMID- 6250263 TI - Renal nuclear imaging and analysis in pediatric patients. AB - Because a renal scan reflects the physiologic configuration and function of the kidney, it provides information that cannot be obtained with conventional intravenous pyelography. It is particularly useful in children with hydronephrosis, vesicoureteral reflux, chronic pyelonephritis, and congenital renal anomalies. PMID- 6250265 TI - Computed tomography in the evaluation of pediatric genitourinary disease. AB - Traditionally, urography has been the diagnostic imaging technique of choice in children with renal and retroperitoneal diseases. However, ongoing experience with abdominal CT in the pediatric patient suggests that CT may be superior to more conventional modes of evaluation for certain urologic conditions, including renal masses and blunt abdominal trauma. PMID- 6250264 TI - Ultrasonography of the urinary tract in children. AB - The various urologic abnormalities for which ultrasonography can be a valuable diagnostic tool are discussed, including renal masses, nonfunction of the kidney, and abnormalities of the lower urinary tract. Ultrasonography is a useful adjunct to radionuclide imaging, intravenous urography, and renl angiography, and is particularly well suited for the pediatric population. PMID- 6250266 TI - [Mucous adenocarcinoma of the urinary bladder (urachal carcinoma) (author's transl)]. AB - A report is presented of 5 cases of urachal carcinomas (3 women and 2 men). The mucous adenocarcinomas were located on the apex of the urinary bladder. In 3 cases partial cystectomy and in 2 cases a subtotal cystectomy were performed. Two patients were treated with cytostatics postoperatively. The prognosis of urachal carcinomas is poor. 3 patients had metastases to the bones, cerebrum and peritoneum. Diagnostic and therapeutic procedures are discussed. PMID- 6250267 TI - Bladder cancer following administration of cyclophosphamide. AB - The relationship between cyclophosphamide and hemorrhagic cystitis is well documented; its role in inducing bladder cancer is less clear. To date, 18 cases of cyclophosphamide-associated bladder tumors have been reported. We present 3 additional cases of transitional cell bladder cancer, all preceded by hemorrhagic cystitis. Data implicating cyclophosphamide as a direct carcinogen as well as an immunosuppressive agent allowing bladder tumor development in the compromised host are discussed. While no direct relationship has been established, we suggest patients receiving this drug are at risk for developing bladder cancer, more likely transitional cell rather than squamous cell as has been reported previously. PMID- 6250268 TI - Case profile: Wilms tumor completely obstructing inferior vena cava without invasion. PMID- 6250269 TI - [State of the organ of vision in workers in the diamond-processing industry]. PMID- 6250270 TI - Peripheral nerve disease in the dog and cat. PMID- 6250271 TI - Diseases of the cerebellum. PMID- 6250272 TI - Viruses associated with diseases of the urinary tract. PMID- 6250273 TI - [Dynamics of maternal and post-infection adenovirus antibodies in fowl]. AB - The epizootological study of the adenovirus infections of poultry, conducted with the use of the serum virus-neutralizing test, gives a picture of the distribution of various serotypes of avian adenoviruses in the poultry population, or in the largest poultry stocks in Czechoslovakia. There is a description of the occurrence of type-specific antibodies in serums of different age categories of poultry acting against seven available virus serotypes. An ascending trend in positive findings of adenovirus antibodies was observed with increasing age of the birds. The dynamics of yolk or maternal antibodies was studied under experimental conditions after the application of virus antigen. PMID- 6250274 TI - Visna-maedi-like disease associated with an ovine retrovirus infection in a Corriedale sheep. AB - A visna-maedi-like disease was found in a Corriedale sheep from which a retrovirus sharing the group antigen of visna-progressive pneumonia virus was isolated from lung, brain, and spleen. Clinically, the sheep had acute neurologic signs and dyspnea. Pathologic examination showed lesions similar to both visna and maedi. In the lung, there was a patchy interstitial pneumonia with marked lymphoid hyperplasia. Changes in the central nervous system were necrotizing nonsuppurative encephalitis of the brain stem, poliomyelitis of the cervical cord, and ependymitis and subependymal gliosis of the ventricles. Histologically, the central nervous system lesions seemed to have arisen sequentially, perhaps in response to bursts of virus replication as the agent underwent possible antigenic mutation. The severe lesions in both the central nervous system and lungs suggested a virus strain with dual tropism. PMID- 6250275 TI - Cholangiocarcinoma in a Capuchin monkey (Cebus albifrons). PMID- 6250276 TI - Some particularities of Sendai virus multiplication in chorioallantoic membrane fragments. AB - Marked differences were recorded in the kinetics of infectant and hemagglutinating (HA) activities of parinfluenza type 1 (Sendai) virus grown in chorioallantoic membrane (CAM) fragments in roller tubes with or without daily changes of the culture medium. The differences were dependent on cultivation conditions, the time interval post inoculation and the state of the CAM cells. Taking into account these conditions, it is possible to obtain either highly infectant virus or virus with low infectivity but high HA activity. PMID- 6250277 TI - Investigations on the presence of papova virus in certain forms of human cancer. Note I. Renal tumors and melanomas. AB - Within the framework of their research concerns regarding the presence of papova viruses in the human population of Romania, as well as the relationship between these viruses and certain forms of human cancer, the authors undertook an electron microscopic study of 4 renal tumors and 6 melanomas. No viral particles could be made evident in any of the sections examined. Viral SV-40 antigen was detected by indirect immunofluorescence reaction in kidney sections from a nephrosis case considered as control. PMID- 6250278 TI - Inhibition of mengovirus RNA-dependent RNA polymerase by an isatinisothiosemicarbazone and a piperidine-thiocarbonyl-hydrazone derivative in a cell-free system. AB - The inhibitory action of two antiviral compounds used at the maximum tolerated dosis in a cellular system led to a complete suppression of the infectious mengovirus yield and to a 100% plaque reduction. The products of the RNA polymerase reaction catalyzed by the microsomal-mitochondrial fraction of mengovirus-infected FL cells were analyzed by linear sucrose gradient centrifugation and polyacrylamid gel electrophoresis. The results showed that the inhibitors cause a general reduction of the synthesis of single-stranded viral RNA. The influence on double-stranded viral RNA was more obvious in the case of the isatinisothiosemicarbazone derivative. PMID- 6250279 TI - The absence of precipitating antibodies to the glycoprotein and p24 fractions of bovine leukemia virus in humans. PMID- 6250280 TI - Influence of 2,4,6-triamino-pyrimidyl-5-azobenzene on the activities of acid phosphatase, alkaline phosphatase and lactate dehydrogenase in cell cultures infected with herpes simplex virus type 1. AB - Treatment of VERO cells with 2,4,6-triamino-pyridimyl-5-azobenzene (10 gamma/ml) one hour after inoculation of herpes simplex virus type 1 limits the influence of the virus infection, consisting in the enchancement of the activities of alkaline phosphatase, acid phosphatase and LDH (especially of the latter two enzymes) and in changes in the isoenzyme patterns of acid and alkaline phosphatases and of peroxidase. In general the influence of the drug is expressed both by the fact that enzyme levels in homogenates of infected cells become closer to the values recorded in controls, and by modifications in the isoenzyme patterns altered by virus multiplication, making them more similar to those of uninfected, untreated cells. PMID- 6250281 TI - Specific protection against bovine leukemia virus infection conferred on cattle by the Romanian inactivated vaccine BL-VACC-RO. AB - The Romanian BL-VACC-RO vaccine against bovine leukemia virus (BLV) infection was prepared with ethylenimine-inactivated BLV obtained from persistently infected cell lines. Intramuscular administration of two vaccine doses (each containing 0.40 mg virus glycoprotein with adjuvant), 2 weeks apart, conferred protection against challenge infection with BLV on 18 of the 20 vaccinated calves. Two calves were not protected, in spite of their positive serologic response to vaccination. The results demonstrate the efficiency of the BL-VACC-RO vaccine in preventing BLV infection. PMID- 6250282 TI - [Secretion of growth hormone, ACTH, and cortisol in humans under conditions of acute hypoxic stress]. PMID- 6250283 TI - [Clinical value of polyposition quantitative 99mTc-pyrophosphate and 99mTc-sulfur colloid scintigraphy in assessing the degree of spreading of tumorous process in lymphogranulomatosis]. AB - To assess the degree of tumor proliferation radionuclide studies were performed in 187 patients with lymphogranulomatosis. Scintigraphy was conducted with 99mTc pyrophosphate and 99mTc-sulfur colloid on gammer chambers FO GAMMA LFOV and OH 110 subsequently followed by processing a scintigraphic image on special-purpose computers CDP 11/34 and OH DC 160. The signs of bone affection revealed by 99mTc pyrophosphate were supported in 86% of cases roentgenotomographically and histologically. A correlation between scintigraphic findings and the results of morphological studies in 45 patients showed a coincidence of the results in 93% of the cases with scintigraphy of the liver and in 81% of cases with radionuclide examination of the spleen by 99mTc-sulfur colloid. A statistical analysis has indicated that scintigraphic findings are consistent with histological ones qualitatively, the probability value being p > 0.999 (X2 = 15.35). PMID- 6250284 TI - [Effect of the physiological status of culture on herpes simplex virus type 2 infection of synchronized cells BNK-21]. AB - Infecting of synchronized cells-BNK-21 by herpes simplex virus type 2 in the S period resulted in a secondary rise of the labeled cells index and shortened time of the cell cycle as a whole. While infecting of the cells during the S period some morphological transformation was observed. The infecting of the cells in the periods M, G1, G2 revealed no essential changes in cell DNA synthesis and failed to result in any cell transformation. PMID- 6250285 TI - [Transforming effect of RNA isolated from polysomes of virus-induced sarcoma]. PMID- 6250286 TI - [25-hydroxycholecalciferol and 24,25-dihydroxycholecalciferol content on rat tissues in vitamin D poisoning]. AB - As vitamin D3 dose increases, the level of 25-hydroxycholecalciferol in the blood plasma, liver, kidneys, small intestine, bones and muscles of rats rises. The maximum concentration and maximum content of 25-hydroxycholecalciferol with reference to the entire tissue growing with vitamin D3 dose increase are characteristic for the osteal tissue. The synthesis of excess quantities of 25 hydroxycholecalciferol is followed by formation of a metabolite that is similar to 24,25-dioxycholecalciferol from the standpoint of chromatographic mobility. The metabolite is accumulated in the kidneys, intestine, blood plasma and to a less measure in the osteal tissue. No metabolite could be detected in the liver or muscles. PMID- 6250287 TI - [Correlation of the nitrate and ascorbic acid content in vegetables and fruits]. AB - Comparison of the evidence on the content of nitrates and ascorbic acid in vegetables and fruits shows that the content of ascorbic acid in fruits exceeds that of nitrates whereas in a number of vegetables the nitrate content is greater than that of ascorbic acid. With increase in the amount of nitrogen fertilizers introduced, the content of nitrates in vegetables grows more intensively as compared to ascorbic acid. The range of these variations is relative to the type and grade of vegetables. During the storage of beet and cabbage the decreased content of ascorbic acid correlated well with the amount of nitrogen-containing mineral fertilizers introduced. It is recommended that fruits and berries be used first of all as a source of ascorbic acid, while rhubarb, fall radish and salad be restricted in the diet. PMID- 6250288 TI - The effect of presynaptic alpha blocker yohimbine on rat paradoxical sleep. AB - In rats, the presynaptic alpha-receptor blocking drug yohimbine given at low doses increases paradoxical sleep (PS) while much higher doses are necessary to depress it. These results are in line with the postulated preferential affinity of this drug for presynaptic noradrenergic (NA) receptors, resulting in an increased activity in NA synapses. The depression of PS under high doses of yohimbine may be related to a post-synaptic blockade of NA receptors, thus cancelling the presynaptic effect. This type of study illustrates the necessity of investigating the temporal evolution of PS instead of simply counting its total amount in a given period of time. PMID- 6250289 TI - Hepatoma. PMID- 6250290 TI - [Neoplastic skin changes after radiotherapy of breast cancer]. PMID- 6250291 TI - [Mixed tumor of the skin]. PMID- 6250293 TI - [Allergy as a typical pathological process]. AB - Allergic reactivity has features of a typical pathologic process and can not be regarded as a "mistake" in the function of the immune system. The sensitivity of the allergic reactivity indicating the entrance of antigenic material into the organism is essentially greater than the sensitivity of all other known reactions of immunity. Reactions on the membrane of target cells after antigen-antibody reaction are not followed by cell damage. Cellular changes after release of allergic mediators are the same ones as in other secretory cells. The mediator liberation is not a result of alteration but of an activation of target cell functions. Allergy developed in the evolution after formation and on the base of immunity and inflammation. Allergy is the combination of specifity of immunologic reaction and more general effects of inflammation. Insufficiency of tissue barriers may be caused by genetic or environmental factors. This insufficiency is possibly the main factor "to be or not to be" of allergy. The allergic reactivity is not an exception but the rule, if an antigen enters into the organism. PMID- 6250292 TI - High dose propranolol in the treatment of angina pectoris: relationship of dose to blood levels and hemodynamic consequences. AB - Propranolol blood levels and the effect of these levels on hemodynamic parameters were evaluated in 25 patients with coronary artery disease undergoing cardiac catheterization and coronary angiography. Fifteen patients were receiving high doses of propranolol (320--1920 mg/day) while ten patients were receiving conventional doses (80--240 mg/day). The high dose propranolol group had significantly higher plasma propranolol levels than the conventional dose group (788 +/- 134 SD vs. 43 +/- 7.2 ng/ml SD), and there was a direct linear relationship between propranolol dose and plasma drug levels (r = 0.85, P < 0.001). There were no significant differences between high and conventional dose propranolol groups in terms of all hemodynamic parameters measured, namely ejection fraction, ventricular volume, cardiac index, or peripheral vascular resistance. Despite high drug dosage and blood levels, only mild side effects were seen. PMID- 6250294 TI - [Therapeutic aspects of endoscopic polypectomy]. AB - 466 endoscopic polypectomies of the upper and lower gastrointestinal tract were analysed according to their curative value. In 254 removed polyps of the upper gastrointestinal tract the result of the histological examination was twice a proof of a carcinoma. One it had to be after-resected, once a carcinoid, five times bleeding polyps were removed. Four times prolapsing gastric polyps were removed in the bulbus duodeni. In these cases intermittent disturbances of the passage could be repaired. Thus the endoscopic polypectomy in the upper gastrointestinal tract was of therapeutic value in 4.3%. In the lower intestinal tract in 204 polypectomies 16 focal carcinomas or invasive carcinomas removed in the healthy tissue, 1 carcinoid and 98 bleeding adenomas were cut away. Thus the coloscopic polypectomy was connected with a therapeutic use in 56.3%. 81.8% of the polyps was tubular, papillary or villous adenomas. Taking into consideration the "adenoma-cancer-sequence", the coloscopic polypectomy must thus be regarded as a prophylactic and curative method, while in the polypectomy in the upper gastrointestinal tract the diagnostic value is in the first place. PMID- 6250295 TI - [Ainhum and a pseudo-ainhum syndrome. Overview with 2 case reports]. AB - In a case of a 26-year-old African Ainhum-Syndrome is reported and compared with a Pseudo-Ainhum-Syndrome by a 44-year-old German woman with chronical Polyneuropathy. Short description of both syndromes. PMID- 6250296 TI - [Insulin and glucagon in the blood plasma of partial hepatectomized rats (author's transl)]. AB - Up to 4 weeks after partial hepatectomy the concentrations of immunoreactive insulin and glucagon in the blood plasma of rats were determined. Furthermore we measured the activity of acid phosphatase in the serum, the concentration of cyclic AMP in liver cells, the activities of acid phosphatase in whole liver cells and in the cytosol of liver cells after partial hepatectomy. 2 h after partial hepatectomy there was a decline of the concentration of insulin in the plasma to about 13% of the initial value. 12 h after surgery a 5-fold increase of glucagon was found in the plasma. Shortly after this cyclic AMP reached its highest concentration. The activity of acid phosphatase in the whole liver cells and in the cytosol decreases slightly in the first 24 h after surgery whereas there is an increase of the activity of acid phosphatase in the serum. PMID- 6250297 TI - Construction of phylogenetic trees by pattern recognition procedures. AB - The sequence of a protein can be graphed as a discrete function and a cross correlation between any two such number sets produces a similarity score. The scores are used to prepare a phylogenetic tree involving hierarchical cluster analysis, non-linear mapping, and minimal spanning routines. Changes are suggested in the sequences of cytochrome c's from Mediterranean fruit fly, locust, and rattlesnake. The method is faster than existing procedures and does not require human intervention at any stage. PMID- 6250299 TI - [Detection of hepatitis A and B markers in the bone marrow of patients with chronic active hepatitis]. PMID- 6250298 TI - [Cavernous hemangioma of the palm with symptoms resembling carpal tunnel syndrome]. AB - In two adults with cavernous hemangiomas occurred symptoms similar to carpal tunnel syndrome. When the angiomas were removed the pains as well hypaesthesia and hypoalgesia in the median nerve area disappeared completely. While in one patient this result stayed on, in the other the same symptoms reappeared when hemangioma recurred. Ischemia in the median nerve area is supposed to be due to shunts in the hemangioma. Their existence could be noticed angiographically as well as histologically in operation specimens. PMID- 6250300 TI - [Enzymes of the "salvage" pathways of RNA and DNA pyrimidine precursor synthesis in hepatomas and tissues of normal and tumor-bearing animals]. PMID- 6250301 TI - [Role of cyclic nucleotides in regulation of the tumor process]. PMID- 6250302 TI - Pathogenicity of ratpox virus for laboratory mice. PMID- 6250303 TI - [System for effecting the action of cyclic adenosine monophosphate in skeletal muscle during chicken ontogeny]. AB - Studies have been made on the possibility of realization of cAMP regulatory action on carbohydrate and calcium metabolism of skeletal muscles in chick embryos. It was shown that during embryonic period cAMP does not activate phosphorylase system and does not inhibit glycogen synthetase. It was found that the absence of any influence of cAMP on these enzymes of carbohydrate metabolism in embryonic muscles does not depend on the state of cAMP-dependent protein kinase, since this enzyme is functionally active. In contrast to the enzymes of carbohydrate metabolism, Ca2+, Mg2+-ATPase of sarcoplasmic reticulum is sensitive to stimulation by cAMP at least from the 2nd week of embryonic development. It is concluded that embryonic skeletal muscles of chicks exhibit all the conditions which are necessary for realization of the regulatory effect of cAMP. Yet the realization of any effect of the nucleotide depends on the maturity of the given effector link. PMID- 6250304 TI - [Role of cholinergic mechanisms in central regulation of respiratory activity in Periplaneta americana cockroaches]. AB - Studies have been made on cholinergic mechanisms in the thoracic ganglion of the cockroach P. americana. It was shown that cholinergic systems are involved not only in the transmission of excitation, but in realization of the inhibitory effects as well. Both types of cholinereceptors were found on motoneurones. Nicotinic, muscarinic or both of the cholinoreceptors may be present on a single interneurone. Nicotinic cholinoreceptors play key role in transmission of excitation. Both types of the cholinoreceptors are involved in realization of the inhibitory influences. PMID- 6250305 TI - [Renal sodium-potassium ATPase during adaptation to different factors in the environment of rats and Citellus flavus susliks]. AB - Seasonal changes in the activity of microsomal transport Na, K-ATPase from cortical, medullar and papillary zones of the kidney have been studied in rats kept under constant laboratory conditions. Maximum activity of the enzyme was found in all kidney zones during May and December-January periods (up to 70%). The lowest level of the activity was observed in summer, especially in July (up to 30-40%). In the ground squirrels, the activity of transport ATPase decreased significantly in all kidney zones within 3 weeks of keeping the animals in the laboratory. PMID- 6250306 TI - [Diagnostic value of detecting neutralizing antibodies to Coxsackie B enteroviruses in patients with infectious-allergic myocarditis]. AB - The clinical virological survey of 180 cardiological patients aged 16-60 years with clinically diagnosed infectious allergic myocarditis (100), rheumatism (38) and other cardiac diseases (42) was made. A group of 97 practically healthy adults aged 21-60 years was used for control. The survey revealed statistically significant differences in the frequency of occurrence of Coxsackie B virus in healthy persons and in cardiac patients. Thus the criteria of the diagnostic significance of the results of the serologic survey gave grounds for suspicion that diseases in 31.2% of the surveyed patients were connected with the presence of Coxsackie B virus infection. Significantly more frequently Coxsackie B virus infection (predominantly type 4 virus) was found to be associated with infectious allergic myocarditis (42%). PMID- 6250307 TI - [Experimental development of immunity to pertussis]. AB - Experiments on animals inoculated intracerebrally with B. pertussis culture No 18 323, serovar 1.2.3, revealed that among sera against B. pertussis strains of different serovars sera against the strains of serovar 1 showed the highest protective potency, and sera against the strains of serovar 1.2 showed the lowest protective potency. In active immunization experiments vaccines from the strains of serovar 1 proved to be least effective, while the immunogenic properties of vaccines from the strains of serovar 1.2 were found to be most pronounced. Since this discrepancy in the above results is due to the fact that the strains of serovar 1 in small doses were unable to create a stable focus of antigenic stimulation, it is not expedient to include strains belonging to serovars other than 1.2 into vaccinal preparations. PMID- 6250309 TI - [Diseases of the lumbosacral division of the peripheral nervous system in children and adolescents]. AB - The clinical picture and course of diseases affecting the lumbosacral division of the peripheral nervous system in 111 children and adolescents aged 8 to 18 years are described. It was found that in 40.5% of the patients the diseases developed in the presence of congenital anomalies in the development of the lumbosacral part of the vertebral column. Unlike adults, the pain syndrome in children and adolescents is less pronounced, and leading in the clinical picture are signs of reflectory-tonic protection of the vertebral column. PMID- 6250308 TI - [Pathogenesis of spinal osteochondrosis and its neurologic manifestations at different ages]. AB - The paper deals with the modern pathogenetic concepts of vertebral osteochondrosis in the age aspect. It was demonstrated that most frequently vertebrogenic lesions of the peripheral nervous system appear in patients aged 30 to 50 years. The role of different pathogenetic mechanisms in the development of the disease (biochemical, autoimmune changes in the intravertebral discs, the state of the higher nervous acitivity, the vestibular apparatus, etc.) was investigated. Pathomorphological studies permitted to establish certain correlations between the intensity of the generative-dystrophic changes in the lumbar part of the vertebral column and the level of the blood supply. Vertebral osteochondrosis can be considered as a polyetiologic but monopathogenetic disease, the clinical signs of which depend upon different endogenous and exogenous factors. The clinical traits of vertebrogenic diseases of the peripheral nervous system in children and adolescents, as well as in patients of old age are described. PMID- 6250310 TI - [Local anomalies and secondary degenerative-dystrophic damage in the craniovertebral region]. AB - Clinical and x-ray studies of patients with focal anomalies of the osteoarticular apparatus of the craniovertebral area demonstrated that half of the cases showed early complications in the form of secondary degenerative-dystrophic lesions. This process is aggravated proportionally to the degree of pronounced interrelation disturbances and overstrain in the craniovertebral area. The secondary degenerative-dystrophic lesions indicate disordered compensation and significantly aggravate the clinical state and working capacity of the patients. PMID- 6250311 TI - Identification of crystals in joint fluids. AB - The inflammatory process present in synovial arthritic specimens can be diagnosed by crystal-type identification performed in cytopathology laboratories by the use of simple methods. These methods involve wet coverslipped preparations of fresh fluid specimens or sediments and compensated polarizing microscopy, which can be performed with a routine microscope equipped with polarizing filters and a substitute compensator. Details of the methodology are described. The morphologic characteristics of the crystals are described in cases of gout, pseudogout and arthritis of other types in which secondary calcifications are present. PMID- 6250312 TI - Double primary lung cancers: with special reference to their exfoliative cytology and to the rare, malignant "mixed" tumor of the salivary-gland type. AB - Two autopsy cases are reported in which double primary cancers of the lung had been strongly or definitely suspected before death by demonstration of two different types of malignant cells in the sputum as well as in smears of aspirates from pleural fluid and/or mediastinal tumor. By exfoliative cytology, one case was characterized by carcinoma cells of the small-cell type plus the large-cell and/or adenocarcinoma type; the other displayed small-cell-type and squamous-cell-type malignant cells. The autopsies definitely revealed in the first case an anaplastic carcinoma of the small-cell type in the left bronchus and a salivary-gland-type malignant "mixed" tumor in the right lower lobe and in the second case an anaplastic carcinoma of the small-cell type in the right upper lobe and a squamous-cell carcinoma in the left upper lobe. The frequence of occurrence and pathologic diagnosis of double primary lung cancers are reviewed and discussed. A rare type of lung cancer, salivary-gland-type malignant "mixed" tumor, is given special reference. PMID- 6250313 TI - Kinins in blood and urine with special reference to intrarenal kinin formation in normal and hypertensive individuals. PMID- 6250314 TI - Iodothyronine release from the perfused canine thyroid. PMID- 6250315 TI - Absorbable sutures (Dexon and Vicryl) in the corneolimbal incision. Used in lens implantation surgery. AB - In 115 consecutive cataract extractions with implantation of artificial lens a clinical evaluation of absorbable sutures--polyglactin (910) (Vicryl 7-0) and polyglycolic acid (Dexon 8-0)--in corneolimbal incision has been performed. The corneolimbal wounds were closed by continuous suture technique with one double loop knot at the 12 o'clock and 5-6 loops on each side of the 12 o'clock knot. The suture had disappeared after 8 weeks in 95% of the eyes. Two months after operation the visual acuity, the power of corneal astigmatism and astigmatic orientation remained unchanged in both the Vicryl and the Dexon sutured group. This provided effectuation of early full prescription of glasses. Most complications in this material were suture independent and appeared during the early postoperative period. In only one eye inadequate wound closure was noticed. Shallow anterior chamber and hypotonia of short duration occurred in 5 eyes. Four of these patients developed corneal dystrophy. In the Vicryl sutured group suture reactions took place in 87% of the eyes. With dexon suture no such reaction appeared. The use of absorbable sutures in corneolimbal incision technique implies several surgical advantages and is seemingly safe. PMID- 6250317 TI - Hair cell damage in the guinea pig due to different kinds of noise. AB - Guinea pigs were exposed in groups of five animals to intense pure-tones or impulse noise, where either the intensity or the exposure duration was varied. The damage to the inner ear was analysed histologically and the loss of outer hair cells was used as damage parameter. The intensity in the pure-tone experimets was varied from 102 to 120 dB sound pressure level. The hair cell damage was not increasing proportionally over the entire intensity range. Above a certain critical level of intensity the damages started to increase more rapidly. This could be explained by theories stating that different mechanisms are responsible for the damage below and above the critical level. When the animals were exposed to impulse noise and the duration of the exposure was doubled the hair cell damage was also doubled up to an exposure time of 24 hours. At longer durations the increase of the damage seemed to level off. Animals exposed to impulse noise for 6 hours and with an equivalent sound level of 102 dB showed slightly higher mean damages than animals exposed to a corresponding continuous pure-tone. The results indicate that the total energy concept is a too simplified hypothesis concerning inner ear damage. PMID- 6250316 TI - An uncommon apudoma: a functional chemodectoma of the larynx. Report of a case and review of the literature. AB - The authors report a case of laryngeal chemodectoma in a 53-year-old man who died from general dissemination and lymphatic and subcutaneous metastases. This functional neoplasm secreted calcitonin revealed by fluorescence and biochemical tests and perhaps adrenaline-like substances. Its cells looked like the light chief cells of the human carotid body; they contained secretory granules and lysosomal formations. Thirty similar cases had been previously reported. The superior laryngeal glomi and more occasionally the inferior ones were the seat of these tumours which occurred with an equal frequency in both sexes. A hoarseness was often the unique symptom noticed during the several months or years preceding the first examination of this slow growing neoplasm. Nevertheless among the chemodectomas of the head and the neck region those arising in the larynx had the highest incidence of malignant evolution. Five of the patients presented a general dissemination, two had lymphatic metastases and one a local recurrence. The ultra-structural features and sometimes the rarely detected functional activity of these chemodectomas are those of apudomas whose cells might originate from the cephalic portion of the neural crests. PMID- 6250318 TI - Effect of papaverine analogues on 3', 5'-adenosine monophosphate phosphodiesterase activity in rat brain. AB - In vitro studies were carried out of some hydrated papaverine analogues on the rat cerebral phosphodiesterase (PD). The potential inhibitory effect of the newly synthesized drugs (Trifonov, Orahovats, 1978), as well as the effect of papaverine, were studied in a series of concentrations (1 micrometer to 100 micrometers) on brain homogenates. The enzyme activity was determined by the isotope method of Filburn and Karn (1972) at two substrate concentrations (1 and 200 micrometers). Dihydropapaverine was found to have practically no effect. 6' Iodo-dihydropapaverine is a weaker inhibitor of the enzyme with low Km, compared with 6'-bromo-dihydropapaverine, however, unlike it its effect on PD with high Km is more marked. Among the compounds tested, papaverine is the most powerful inhibitor of the enzyme with low and high Km. The kinetic analysis of PD with low and with high Km, performed after Lineweaver and Burk, has shown hat the inhibition of the enzyme by the studied substance is reversable and of the competitive type. The inhibitory constants of the compounds studied were estimated. PMID- 6250320 TI - Effect of chronic treatment with tricyclic antidepressant drugs on identified brain noradrenergic and serotonergic neurons. PMID- 6250319 TI - [Gastric secretory receptors]. PMID- 6250321 TI - A neuroendocrine study of adrenoceptor function in endogenous depression. PMID- 6250322 TI - Effect of peptide fraction of cerebrospinal fluid from patients with post traumatic brain oedema on ATP-ase activity in erythrocyte shadows. PMID- 6250323 TI - Attempts to develop super- or subsensitivity of retinal dopamine receptors after various treatments with antagonists or agonists. PMID- 6250324 TI - Short- and long-term effects of GABA and dopamine neurons during treatment with sulpiride. PMID- 6250326 TI - Chronic effects of alcohols on mouse biomembranes. PMID- 6250325 TI - The sequential analysis of cancer development. PMID- 6250327 TI - Cyclic AMP and beta-adrenergic receptors during the development of physical dependence on ethanol in the rat. AB - 1. The half-time for maximal withdrawal scores in the rat is 30 to 36 hours following around the clock intubation with ethanol. 2. Cyclic AMP levels in all brain areas decline with ethanol treatment and rise again to control levels during withdrawal. 3. Norepinephrine-stimulated adenylate cyclase activity is increased by chronic treatment with ethanol. However, it is unlikely that this change is related to physical dependence, as it occurs 50 to 60 hours following the development of half-maximal withdrawal scores. 4. Ethanol had no effect on the concentration of beta-receptors in the cerebral cortex. PMID- 6250328 TI - Rat brain cyclic AMP levels and withdrawal behavior following treatment with t butanol. AB - 1. The time course development of physical dependence as assessed by the withdrawal reaction was identical for ethanol and t-butanol. 2. t-Butanol is most likely not metabolized by the liver and is eliminated from the rat 6 to 7% as rapidly as ethanol. 3. Blood and brain acetaldehyde could not be detected following treatment with t-butanol. 4. At the peak of withdrawal, cyclic AMP levels were indistinguishable from control values following treatment with either ethanol or t-butanol. PMID- 6250329 TI - Effect of ethanol on neural cells grown in culture: interaction with plasma membrane ecto-5'-nucleotidase activity. AB - The effect of ethanol on an enzyme system within an intact functional plasma membrane has been studied using neural cells grown in culture. Rat C6 glioma cells in mono-layer culture were treated acutely or chronically with 100 mM ethanol and the effect of this exposure on the activity of ecto-5'-nucleotidase was determined. Acute exposure led to an increase in enzyme activity with maximum stimulation occurring at concentrations of 100 - 400 mM ethanol. Chronic treatment of cells with 100 mM ethanol for 4 - 8 days also caused an increase in ecto-5'-nucleotidase activity. Both the acute and chronic ethanol-induced stimulation of enzyme activity was completely reversible by removing the ethanol; the acute effects reversed immediately, whereas the chronic effects required several hours. The addition of Concanavalin A demonstrated that the effects on enzyme activity of both chronic and acute exposure to ethanol were blocked by modification of the external cell surface. The effect of chronic exposure to 100 mM ethanol was further localized to an action on the plasma membrane by studies which showed chronic exposure to have no effect on the intracellular 5' nucleotidase activity. Furthermore, the occurrence of pharmacological tolerance to acute ethanol was observed in this plasma membrane system following chronic treatment of C6 cells with 100 mM ethanol. These findings are consistent with the hypothesis that mammalian neural cells can adapt to the chronic presence of ethanol through changes in their plasma membrane. PMID- 6250330 TI - The effects of thyrotropin-releasing hormone (TRH) and other drugs on the actions of alcohol. PMID- 6250331 TI - Effects of lithium chloride on human and murine marrow myeloid colony formation and colony stimulating activity. PMID- 6250332 TI - Biology of the lithium ion. PMID- 6250333 TI - Higher leukocyte nadirs with lithium carbonate after chemotherapy. PMID- 6250334 TI - Effects of lithium on polymorphonuclear leukocyte chemotaxis. PMID- 6250335 TI - Effects of lithium on neutrophil metabolism in vitro and on neutrophil function during therapy. PMID- 6250336 TI - The bactericidal defect of neutrophil function with lithium therapy. PMID- 6250337 TI - Characterization of lithium effects on two aspects of T-cell function. AB - Cell surface receptors receive, transduce and relay a variety of environmental signals. These phenomena, which have been extensively characterized in non lymphoid cells, also appear to play a crucial role in dictating the degree of lymphocyte responsiveness. The nature of these regulatory events is only beginning to be unraveled but the adenylate cyclase-cyclic AMP axis appears to be one of the important controlling systems. Lithium appears to be as important a modulator of lymphocyte responsiveness as previously shown for a variety of other cells and the mechanism of action, in general, is consistent with its role as a putative blocker of adenylate cyclase activation. Indeed, lithium may exert its role as a regulator of lymphocyte responsiveness by acting on specific lymphocyte subpopulations. Direct proof for this is still wanting and consideration of its capacity for action as an imperfect substitute for normal extra- or intracellular cations or on the physiochemical state of the plasma membrane is necessary. Nevertheless, these studies indicate the validity of using lithium for assessing the role of the lymphocyte adenylate cyclase-cyclic AMP system in the generation and expression of regulatory signals leading to modulation of the immune system. PMID- 6250338 TI - The effect of lithium upon granulocyte production in vitro and in vivo in the mouse. PMID- 6250339 TI - The biochemistry of the renin-angiotensin system. PMID- 6250340 TI - Inhibitors of angiotensin-converting enzyme. PMID- 6250342 TI - Interactions between the renin-angiotensin system and the brain. PMID- 6250341 TI - Role of angiotensin II in the regulation of aldosterone biosynthesis. PMID- 6250343 TI - Comparative endocrinology of renin and angiotensin. PMID- 6250344 TI - Receptor-adenylate cyclase components: abnormalities in clinical medicine. PMID- 6250345 TI - Cyclic nucleotides in hypertension. PMID- 6250346 TI - On the mechanism of cyclic AMP-mediated growth arrest of solid tumors. PMID- 6250347 TI - Cyclic AMP-dependent protein kinase type I and type II and cyclic AMP binding in human mammary tumors. PMID- 6250348 TI - Cyclic nucleotides and the control of psoriatic cell function. PMID- 6250349 TI - Editorial comments: cyclic nucleotides and cellular events related to cell growth. PMID- 6250351 TI - Cyclic nucleotides and the Chediak-Higashi syndrome. PMID- 6250350 TI - Cyclic nucleotides, beta receptors, and bronchial asthma. PMID- 6250352 TI - Editorial comments: modulation of lymphoid cell function and allergic responses. PMID- 6250353 TI - Cyclic nucleotides in mental disorder. AB - Human CSF cyclic nucleotides do not distinguish manic-depresive patients or schizophrenic patients from controls, although a "high CSF cyclic AMP" subgroup of poor-prognosis schizophrenics is still under investigation. Neuroleptic therapy raises CSF cyclic GMP and lowers CSF cyclic AMP, at least in the responder subgroup of a clinically heterogeneous patient population when neuroleptics that are good adenylate cyclase inhibitors in vitro are used in the treatment. This is consistent with the concept that neuroleptic treatment in humans involves blockade of dopamine neurotransmission. Attempts to correlate the decline in CSF cyclic AMP concentration with clinical improvement may be important. Lithium treatment does not alter the level of CSF cyclic AMP, which probably derives largely from dopamine-related neurotransmission that lithium does not affect. However, the plasma cyclic AMP response to epinephrine is inhibited by lithium at therapeutic doses in vivo after chronic treatment. The lithium effect is somewhat specific in that the glucagon-stimulated rise in plasma cyclic AMP is not affected. The results in clinical experiments support the theory that norepinephrine-sensitive adenylate cyclase inhibition in brain is involved in lithium action. Research to attempt to distinguish lithium-responsive from lithium nonresponsive patients on the basis of sensitivity to lithium inhibition of the epinephrine-induced rise in plasma cyclic AMP is of considerable potential practical importance. PMID- 6250354 TI - Epilepsy and cyclic nucleotides. PMID- 6250356 TI - Altered cyclic nucleotide metabolism and the pathogenesis of hereditary retinal dystrophies. PMID- 6250355 TI - Acute and chronic effects of psychoactive drugs on adrenergic receptors and calmodulin. AB - The effects that psychoactive compounds have on those biochemical mechanisms of brain that influence the metabolism of cyclic nucleotides depend on whether the drugs are administered acutely or chronically. For example, antipsychotic agents acutely block the action of catecholamines on the adrenergic receptor-adenylate cyclase complex, thereby preventing the catecholamine-induced rise in cyclic AMP. But with long-term treatment, which might correspond more closely to the manner in which they are used clinically, the drugs appear to produce a compensatory increase in these catecholaminergic receptors. Repeated stimulation of adrenergic receptors with compounds that block the uptake of catecholamines, such as the antidepressants, produces a decrease in the number of these receptors and a concomitant subsensitivity to the effects of catecholamines on the formation of cyclic AMP. This is in contrast to their acute actions which result in a potentiation of the action of catecholamines. In addition to their effects on catecholamine receptors, clinically-effective antipsychotic drugs also bind to an endogenous calcium-dependent protein termed calmodulin, which is found in high concentrations in the CNS. This binding of antipsychotics to calmodulin can explain several of their biochemical actions and suggests that some of the pharmacological and perhaps clinical effects of these drugs may also be explained by a common mechanism. In fact, the specificity with which antipsychotic drugs bind to calmodulin suggests the possibility of searching for new and clinically more effective antipsychotic agents based on their selective binding to calmodulin. PMID- 6250357 TI - Editorial comments: cyclic nucleotides in the CNS. PMID- 6250358 TI - Cyclic nucleotides and cystic fibrosis. PMID- 6250359 TI - Adrenergic and cholinergic modulation of extracellular cyclic nucleotides. PMID- 6250360 TI - Role of cyclic nucleotides in enterotoxic diarrhea. PMID- 6250361 TI - Editorial comments: cyclic nucleotides and exocrine secretion. PMID- 6250363 TI - Editorial comments: kidney function and cyclic nucleotides. PMID- 6250362 TI - Cyclic nucleotides and tubule function. PMID- 6250364 TI - Cyclic nucleotides in diabetes mellitus and obesity. PMID- 6250366 TI - Editorial comments: cyclic nucleotides in the regulation of storage and mobilization of fuels. PMID- 6250365 TI - Role of cyclic AMP in human adipose tissue lipolysis. PMID- 6250367 TI - The adenylate cyclase-cyclic AMP system in Graves' disease. PMID- 6250368 TI - Adrenergic receptors. PMID- 6250369 TI - FSH stimulation of protein kinase inhibitor: regulation of cellular metabolism. PMID- 6250370 TI - Use of cyclic nucleotides in detection of disturbed parathyroid function. PMID- 6250371 TI - Editorial comments (A): measurement of cyclic nucleotides. PMID- 6250373 TI - Comments on pathophysiological studies and cyclic nucleotides. PMID- 6250372 TI - Editorial comments (B): extracellular cyclic nucleotides. PMID- 6250374 TI - Cyclic nucleotides in heart in acute myocardial ischemia and hypoxia. PMID- 6250375 TI - Evidence for role of cyclic AMP as second messenger of arrhythmogenic effects of beta-stimulation. PMID- 6250376 TI - Cyclic nucleotides in hemostasis and thrombosis. PMID- 6250377 TI - Editorial comments: cyclic nucleotides and the pathophysiology of the cardiovascular system. PMID- 6250378 TI - Growth in children treated with long-term dialysis. A study of 76 patients. PMID- 6250379 TI - Role of the renin-angiotensin-aldosterone system in the regulation of blood pressure. PMID- 6250380 TI - Spontaneously occurring animal models of human kidney diseases and altered renal function. PMID- 6250381 TI - Cellular senescence: cell proliferation and its control. PMID- 6250382 TI - Receptor changes and the control of hormone action during aging. PMID- 6250383 TI - The role of the cell surface and the microfibrils in transformation. PMID- 6250384 TI - Wilms tumor arising from spontaneously regressing nephroblastomatosis. PMID- 6250385 TI - Radionuclide and CT diagnosis: cavernous hemangioma of liver. PMID- 6250386 TI - Hepatic and thoracic amaebiasis. AB - Sonographic and radiographic fidings were reviewed in 27 patients with hepatic amebiasis. Sonography usually demonstrated nonspecific, peripheral, hypoechoic lesions. The only diagnostic sonographic appearance was a combination of a hypoechoic lesion and diaphragmatic disruption, which was found in four patients. About 50% of the patients had accompanying radiographic abnormalities that were nondiagnostic. These included elvation of the right hemidiaphragm, basilar pulmonary infiltrates, and pleural effusions. Liver abscesses occasionally grew during the first 2 weeks of treatment even though the patients were responding well to medical therapy. Lesions frequently became more anechoic and better defined on follow-up examinations. Successfully treated abscesses may calcify rather than diminish. PMID- 6250387 TI - CT of abdominal malignancies: dynamic approach. AB - By sequential CT scanning, the dynamics of intravenously injected contrast medium were observed in 21 patients with abdominal malignancies. Within 30 sec, and one breath, four sequential cuts of the same section were obtained. The corticomedullary junction of the kidney was clearly delineated in the early phase, and tumor vascularity was well appreciated within vascularized malignancies. Angiographic CT was found to be superior to conventional CT and is promising in the assessment of the nature of abdominal tumors. In some cases, use of CT angiography may enable deferring catheter angiography. PMID- 6250388 TI - Intravenous extension of endocrine tumors. AB - Four patients with intravenous extension of endocrine tumors are described. Three had adrenal carcinoma with extension along the adrenal veins into the inferior vena cava. In two of these, the extension into the inferior vena cava was demonstrated by computed tomography. The fourth patient had a glomus jugulare with extension down the jugular vein into the superior vena cava. In ech case preoperative radiologic evaluation demonstrated the tumor and its venous extension. PMID- 6250389 TI - Malignant granular cell myoblastoma with metastatic cardiac involvement: Case report and echocardiogram. AB - A malignant form of granular cell myoblastoma originating in the shoulder, gave rise to metastatic cardiac involvement causing infiltrative cardiomyopathy with heart block. The patient survived four months with a permanent pacemaker. The echocardiographic and histological features are described and the literature is reviewed. Features shown on the echocardiogram are indistinguishable from other causes of infiltrative cardiomyopathies. PMID- 6250390 TI - Inhalation of a radioactively labeled monodisperse aerosol in rats for the assessment of regional deposition and clearance. AB - Unanesthesized male Sprague-Dawley rats, averaging 261 g of weight (s.d. = 9 g), were exposed to a radioactively (198Au) labeled monodisperse carnauba wax aerosol, whose AMMD was 0.54 micrometers with a sigma g of 1.1, to determined the alveolar deposition and clearance of particles. Results indicate that 74% of the initial lung burden is cleared in phase one with a T/2 of 11 hours. The remaining 26%, conventionally considered to be the alveolar deposit, is cleared with a T22 of 320 hours. Excised lungs from serial sacrifices have also been measured. The retention curve resulting form the pooled lung data per each day compared well with the curve of the whole animals counted in vivo. PMID- 6250391 TI - Respiratory function study of Nigerian workers in a TDI-based foam plant. PMID- 6250392 TI - Acute and chronic systemic and pulmonary hemodynamic effects of angiotensin converting enzyme inhibition with captopril in hypertensive patients. PMID- 6250393 TI - Calcium and the secretory cycle of prolactin cells: a cytochemical and ultrastructural study of dopamine inhibition and monobutyryl cyclic AMP stimulation of prolactin secretion. AB - To identify intracellular calcium pools that may be involved in the secretory process in prolactin (PRL) cells, hemi pituitaries were incubated in medium containing 10(-6) M dopamine, 5 mM cyclic cAMP (experimentals), or in medium alone (controls) and then processed for electron microscopy using potassium pyroantimonate to localize intracellular calcium. PRL in the medium was measured by radioimmunoassay. The concentration of antimonate associated with mitochondria, Golgi saccules, and secretory granules was estimated. Dopamine inhibition of PRL secretion (> 80% at 1, 2, 3 h) resulted in accumulation of secretory granules in all stages of maturation and dilation of Golgi saccules at 2 and 3 h, accompanied by increased mitochondria antimonate and increased Golgi associated antimonate. Cyclic AMP stimulation of secretion (635% at 5 min., declining to 34% at 1 h) resulted in marked exocytosis at 5 and 15 min., declining after 30 min. Mitochondrial antimonate decreased after 30 min. Stimulated cells exhibited numerous coated membrane structures at or near exocytotic pits and an amassing of microvesicles at the margin of the Golgi apparatus. Although some secretory granules consistently exhibited reactivity to antimonate (unchanged by inhibition or stimulation), plasma membrane, and granule membrane translocated to the plasma membrane during exocytosis, were not reactive. PMID- 6250394 TI - Diabetic diets: high carbohydrate combined with high fiber. AB - The ideal level of carbohydrate intake for diabetics placed on high-fiber diets is unknown. Nineteen diabetics, therefore, took part in a total of twenty-four 5 day studies of fiber supplementation (guar) with carbohydrate intakes ranging from 22 to 61% of total calories. Where carbohydrate formed more than 40% of the calorie intake, there was a mean 64% reduction in glycosuria over the last 2 days on guar (P < 0.001, 14 studies, 11 patients). No significant reduction in glycosuria was seen in the 10 studies on lower carbohydrate intakes. This suggests that dietary fiber supplements in diabetes should be given against a background of higher rather than lower carbohydrate intake. PMID- 6250395 TI - Dietary fiber: the effect of particle size of wheat bran on colonic function in young adult men. PMID- 6250396 TI - Influence of dietary fiber from vegetables and fruits, bran or citrus pectin on serum lipids, fecal lipids, and colonic function. PMID- 6250397 TI - Alterations in zinc absorption and salivary sediment zinc after a lacto-ovo vegetarian diet. AB - The effect of a lacto-ovo-vegetarian diet on plasma zinc tolerance tests and plasma and saliva zinc levels was measured in 12 nonvegetarian women. A diet meeting the Recommended Dietary Allowances for all nutrients, including zinc, was fed to the subjects for 22 days. Initial zinc status of subjects was determined by zinc analysis of their diet, hair, plasma, and saliva. Plasma response to an oral load of 50 mg Zn was determined in five subjects before and after the dietary period. Zinc levels of salivary sediment, which consisted primarily of epithelial cells, significantly decreased from initial values of 128 to final levels, of 94 microgram/g. No significant differences were found in zinc levels of plasma or whole mixed saliva. Plasma response to initial zinc tolerance tests were inversely correlated (P < 0.05) to dietary protein levels. Significantly increased plasma zinc uptake and areas under zinc tolerance curves were found after consumption of vegetarian diets compared to diets containing meats. The increased plasma response to a zinc load and decrease in salivary sediment zinc after a vegetarian diet indicate that this diet adversely affects zinc status. PMID- 6250398 TI - Inclusion-bearing cells in industrial workers exposed to lead. AB - Histochemical and microscopic studies have shown that a characteristic renal response to lead exposure is the formation of discrete, dense, staining intranuclear inclusion bodies in renal tubular epithelial cells. Cytologic examination of urinary sediment showed that four of 19 (21%) lead workers had exfoliated inclusion-bearing cells of proximal renal tubular origin. These lead induced inclusion-bearing cells appeared distinctly different from viral-induced inclusions, degenerative or nonspecific intranuclear inclusions seen with tubular necrosis, or macronucleoli seen in reparative renal tubular epithelium. While their presence indicates cytologic evidence of tubular injury, the clinical significance of these cells and their application to medical monitoring is not clearly understood. PMID- 6250399 TI - Rotavirus gastroenteritis in the Washington, DC, area: incidence of cases resulting in admission to the hospital. AB - The incidence of rotavirus gastroenteritis in infants and children that required admission to the hospital was estimated for a defined population of approximately 105,000 individuals, including 29,000 children aged 15 years or younger whose primary health care was provided by Group Health Association, Inc, a health maintenance organization in the Washington, DC, area. From January 1977 through March 1979, almost all infants and children in this age group who required hospitalization for gastroenteritis were studied for evidence of infection with human rotavirus (HRV) and other agents. On the average, one in 272 (3.7/1,000) infants less than 12 months old and one in 451 (2.2/1,000) children aged 13 through 24 months were hospitalized for HRV disease each winter. The incidence of rotavirus gastroenteritis requiring hospitalization declined precipitously in children after the second birthday and such illness was not detected in children aged 5 years or older. The role of other agents in acute gastroenteritis requring hospitalization was minimal, compared with that of rotavirus. PMID- 6250401 TI - Acute monoarticular arthritis caused by herpes simplex virus and cytomegalovirus. PMID- 6250400 TI - Computerized tomography to define CNS involvement in congenital cytomegalovirus infection. PMID- 6250402 TI - Asymptomatic virus shedding after herpes genitalis. AB - Samples of cervical and vaginal secretions obtained daily from five women were studied for the presence of active virus and/or viral antigens. In women with a history of recurrent genital herpes, either infectious virus or viral antigen in exfoliated cells was repeatedly detected in the absence of overt clinical symptoms. The epidemiologic and obstetric importance of the observations is discussed. PMID- 6250403 TI - Detection of circulating placental protein 5 in patients with trophoblastic tumors. PMID- 6250404 TI - Management of liver metastasis from gestational trophoblastic neoplasia. PMID- 6250405 TI - Calcium-dependent, parathyroid hormone-independent regulation of 1,25 dihydroxyvitamin D. AB - The increase of plasma 1,25-dihydroxyvitamin D (1,25(OH)2D) in response to Ca restriction has been suggested to be essentially mediated by parathyroid hormone (PTH). In this study, we have assessed the influence of variations in calcium intake on plasma 1,25(OH)2D in pair-fed sham-operated (sham) and in hypocalcemic hypoparathyroid rats after thyroparathyroidectomy (TPTX). In sham rats, plasma 1,25(OH)2D increased from 189 +/- 16 to 486 +/- 41 pM when dietary calcium was inreased from 1.2% Ca to 0.2% Ca. This increase was associated with an increase in plasma PTH level. In TPTX rats, plasma 1,25(OH)2D increased from 112 +/- 9 to 332 +/- 36 pM when dietary calcium was decreased. In this case, the increase was not associated with a rise in plasma PTH level nor with an increase in urinary cyclic AMP. When TPTX rats were infused chronically with PTH (60 U/day), plasma 1,25(OH)2D was 62 +/- 9 pM when the 1.2% Ca diet was given and 281 +/- 45 pM with the 0.2% Ca diet. These reults confirm that the thyroparathyroid glands influence plasma 1,25(OH)2D but they also provide evidence for a PTH-independent response of plasma 1,25(OH)2D to Ca restriction. PMID- 6250406 TI - Beta-adrenergic stimulation of cAMP and progesterone in rat ovarian tissue. PMID- 6250407 TI - Parathyroid hormone modulates protein kinase in giant cell tumors of human bone. AB - The physiological effects of parathyroid hormone (PTH) in bone are mediated at least in part by cyclic AMP. The biochemical events subsequent to this step have not been well characterized in this tissue. Giant cell tumors of bone (GT) increase cyclic AMP in response to PTH. This response can be inhibited by an analogue of bovine PTH, [Nle8, Nle18, Tyr34] bPTH-(3-34) amide (PTH-Inh). Cyclic AMP content and cyclic AMP-dependent protein kinase (cAMP-PK) were assayed in fresh tumors and cells in culture incubated with 1 microgram/ml of bPTH and/or PTH-Inh. PTH fully activated cAMP-PK in GT, and PTH-Inh completely inhibited PTH stimulated increases in cyclic AMP content and cAMP-PK activity. When endogenous protein substrates were sought for cAMP-PK, three phosphoproteins of 55,000, 43,000, and 38,000 mol wt maximally increased their phosphorylation by 30% after 12-min incubation with bPTH. Dephosphorylation of proteins of 200,000 and 120,000 mol wt was also observed. These data are consistent with the hypothesis that PTH action in bone is mediated by the phosphorylation and dephosphorylation of specific substrates. PMID- 6250408 TI - Effect of PTH on calcium transport across the cortical thick ascending limb of Henle's loop. AB - Cortical thick ascending limbs of Henle's loop were dissected from rabbit kidneys and perfused in vitro. Unidirectional transepithelial calcium fluxes from lumen to-bath and bath-to-lumen were measured with 45Ca. The tubules were bathed in 150 mM sodium and perfused with 60 mM sodium to simulate conditions in the cortical thick ascending limb in vivo. During the 20-30 min preceding the addition of parathyroid hormone (PTH), net calcium absorption decreased from 0.207 to 0.084 pmol x s-1 x cm-1. After addition of synthetic bovine PTH (60-64 nM) to the bath, there was an immediate increase in calcium absorption, and by 20 min the net flux increased to 0.415 pmol x s-1 x cm-1. The increase in calcium absorption was due to an increase in the lumen-to-bath flux. Dibutyryl-cAMP or 8-BrcAMP mimicked PTH; adrenocorticotropic hormone had no effect on the calcium flux. Transepithelial voltage was unchanged after addition of PTH. We conclude that PTH increases calcium absorption across the cortical thick ascending limb, probably by stimulation of adenylate cyclase. PMID- 6250409 TI - PTH inhibition of bicarbonate transport by proximal convoluted tubules. AB - These studies examined the effect of parathyroid hormone (PTH), dibutyryl cyclic AMP DBcAMP, and 8-bromo-cyclic AMP BrcAMP on HCO3- transport by rabbit superficial proximal convoluted tubules perfused in vitro. Bicarbonate was estimated as total CO2 measured microcalorimetrically. At slow perfusion rates with 25 mM HCO3- in the perfusate and bath, PTH (0.1 U/ml in the bath) caused the total CO2 in tubular fluid to rise from 10.2 to 19.9 mM. The hormone had no effect on the total CO2 concentration in tubules perfused with HCO3(-)-free perfusates. With HCO3(-) in the perfusate and bath, PTH reduced the rates of fluid and total CO2 absorption to 57 and 48% of control values, respectively. PTH had no effect on the rates of fluid absorption and total CO2 secretion when HCO3( )-free perfusates were used. The effects of DBcAMP and BrcAMP (10(-7) M in the bath) were similar to those of PTH. 5'-AMP (10(-6) M in the bath) did not alter the total CO2 concentration of tubular fluid when the tubules were perfused at slow rates with HCO3- in the perfusate and bath. Ouabain (10(-5) M in the bath) caused the total CO2 concentration in tubules perfused at slow rates with HCO3- free perfusates to rise from 8.9 to 12.7 mM. PTH caused no further change in the total CO2 concentration in the presence of ouabain. PMID- 6250410 TI - The renal sodium pump and vanadate. PMID- 6250411 TI - Stimulus-permeability coupling in rat lacrimal gland. AB - Incubation of isolated cells wtih 10(-2) M ethylene glycol-bis-(beta aminoethylether)-N,N'-tetraacetic acid or cobalt inhibits 22Na and 45Ca uptake stimulated by carbachol. The artificial introduction of Ca into the cytosol by the cation ionophore A23187 also initiates the 22Na uptake. Amiloride (10(-5) M) partially inhibits 22Na uptake induced by carbachol, but has no effect on receptor-stimulated 45Ca uptake or 86Rb release. Tetrodotoxin (TTX) has no effect on 22Na uptake stimulated by carbachol, whereas methoxyverapamil (D 600) produces a small but significant decrease in both 22Na and 45Ca uptake. This effect of D 600 may be related to a block of receptor activation and not to a block of Ca channel activation. Incubation in high K (56 mM) does not prevent the change in membrane permeability to Ca, K, and Na initiated by carbachol. It is concluded that carbachol stimulates the influx of Ca; the rise in the cytosolic Ca concentration then couples receptor activation to a change in membrane permeability to K and Na. The permeability mechanisms for Ca, K, and Na that are activated by carbachol appear to be specific for each of the three cations and appear to be dissimilar to permeability mechanisms in excitable tissue that carry the same ions. PMID- 6250413 TI - Cholinergic intervention in intracardiac autonomic nerves in atrioventricular junctional area. AB - Cholinergic influence on atrioventricular (AV) junctional rhythm via its intervention in the intracardiac autonomic nerves was investigated in the canine, blood-perfused AV node preparation. Large amounts of acetylcholine (ACh) injected into the anterior septal artery (ASA) caused a rapid increase in the rate of automaticity superimposed on a slow increase. Nicotine given in the ASA caused to a rapid increased superimposed on a slow increase. Large amounts of ACh injected into the posterior septal artery (PSA) caused a slow increase, which was superimposed by a rapid icrease in the presence of l-hyoscyamine. The rapid and slow increases were abolished by dl-propranolol given in the PSA and ASA, respectively. Both types of increases were suppressed by tetrodotoxin (TTX). Nicotine given in the PSA caused a decrease superimposed by a rapid increase, both of which were abolished by TTX. These reslts indicate that cholinergic excitatory intervention induces AV junctional tachycardia via norepinephrine release from sympathetic nerve endings, distributing widely from the proximal to distal portion of the AV junctional area. PMID- 6250412 TI - Ca2+-dependent secretagogue stimulation in isolated rabbit gastric glands. PMID- 6250414 TI - Quantitative microautoradiography of arteries: comparison of radioactivity to silver. AB - The local concentration of silver in developed aortic transmural microautoradiographs was compared to the corresponding 125I-labeled albumin radioactivity concentration [ci(x)] in the subjacent tissue. Silver [s(x)] was measured by electron probe X-ray microanalysis (EPA) and the corresponding ci(x) by direct gamma-ray counting. The results show 1) that the relationship between volume-averaged values of radioactivity (ci) and EPA signal (s) is adequately described by ci = Ks, where K is a proportionality constant, and 2) that ci(x) measured by EPA [i.e., Ks(x)] agrees closely with ci(s) measured direcly from en face microtomy slices of corresponding unfixed tissue specimens. PMID- 6250415 TI - Application of thin layer immunoassay (TIA) for demonstration of antibodies against Entamoeba histolytica. AB - Thin layer immunoassay (TIA) was used to demonstrate antibodies against Entamoeba histolytica in sera from patients and blood donors. The TIA results agreed well with those obtained by the indirect hemagglutination (IHA) and immunodiffusion (ID) techniques. It is suggested that because of its technical simplicity and low cost TIA may be used alternatively or in addition to the IHA and ID techniques for screening patient sera for antibodies to E. histolytica. However, the new technique must first be evaluated on a goup of clinically well defined patients with different stages of amebiasis. PMID- 6250416 TI - Transovarial transmission of Japanese encephalitis virus by Culex tritaeniorhynchus mosquitoes. PMID- 6250417 TI - David M. Hume Memorial Lecture. An overview of the stroke problem in the carotid territory. AB - In a review of 1,000 carotid endarterectomies performed over a 20 year period, there was relief of transient ischemic attacks in approximately 85% of patients, an operative mortality of 1.3%, due almost exclusively to myocardial infarction, and a recurrent stenosis rate of 3.1%. Coexisting cardiac disease constitutes the greatest operative hazard. Continuous electroencephalographic monitoring is a reliable method of detecting inadequate cerebral perfusion during carotid cross clamping and for the selective use of a temporary inlying carotid shunt. An atherosclerotic plaque in the carotid system constitutes a greater risk than elsewhere in the peripheral arterial system and should not be considered an innocent lesion. Prophylactic carotid endarterectomy can be performed with almost no mortality and morbidity. Antiplatelet agents, while useful in reducing the incidence of transient ischemic attacks, do not seem to provide equal protection against stroke and death from stroke. PMID- 6250418 TI - [Cellular immunity in uterine trophoblastic tumors]. PMID- 6250419 TI - [Granulosa and theca cell ovarian tumors (a lecture review)]. PMID- 6250420 TI - Masseter spasm after pancuronium. PMID- 6250421 TI - Bovine viral diarrhea infection in pregnant swine. AB - Twenty pregnant gilts (5 groups of 4) were infected experimentally with 1 of 4 strains of bovine viral diarrhea virus (BVDV) administered intranasally-orally. Blood specimens were taken from the gilts on postinfection day (PID) 7 and cultured for virus. Serum specimens, obtained on PID 21 and at termination of the experiment, were tested for neutralizing antibodies. At 90 to 112 days of gestation, the gilts were euthanatized and their fetuses were examined for evidence of intrauterine infection. Evidence of infection was demonstrated in all of the gilts, either by isolation of BVDV at PID 7 or subsequently by detection of neutralizing antibody titers. Intrauterine infection was confirmed in one of 20 gilts by isolation of BVDV, detection of neutralizing antibodies, and demonstration of microscopic lesions in the fetuses. The microscopic lesions were characterized as nonsuppurative meningitis and choroiditis. Clinical signs of disease were not seen in the infected fetuses. Of 8 gilts exposed to strains of BVDV pathogenic for cattle, 1 gilt developed intrauterine infection, 2 gilts were found barren, and 3 gilts had significantly fewer fetuses than copora lutea. PMID- 6250422 TI - Feline chronic progressive polyarthritis. AB - Twenty cats with a chronic progressive polyarthritis were studied. The disorder occurred exclusively in male cats, and all but six of the cats were between 1.5 and 5.0 years of age. There were two forms of the disease as determined by radiographic changes: joint instability and deformity, and clinical course. The most prevalent form of the disease was characterized by osteopenia and periosteal new bone formation surrounding affected joints. Marginal periarticular erosions and collapse of the joint spaces with fibrous ankylosis occurred with time, but joint instability and deformities were not seen. The second form of the disease was characterized by severe subchondral marginal erosions, joint instability, and deformities. The periosteal proliferative form resembled Reiter's arthritis of man, and the deforming type resembled human rheumatoid arthritis. The disease began as tenosynovitis and synovitis, with subsequent changes in the articular cartilage and periosteal bone. Histopathologic changes in these cats were similar to those occurring in both chronic Reiter's and rheumatoid arthritis of man. Chronic progressive polyarthritis of cats was not caused by identifiable bacteria or mycoplasma, but was etiologically linked to feline leukemia virus (FeLV) and feline syncytia-forming virus (FeSFV) infections. The FeSFV was isolated from the blood or was detected by a serologic test in all of the cats with the disease, whereas FeLV was isolated or identified by immunofluorescence technique in 60% of the cats. The arthritis could not be reproduced by inoculation of cell-free cynovial tissue from diseased cats or with tissue culture fluid containing FeSFV and FeLV isolates. It was postulated that arthritis was an uncommon manifestation of FeSFV infection that occurred in predisposed male cats. Feline leukemia virus may not have been directly involved in the disease, but may have acted in some way to potentiate the pathogenic effects of FeSFV. PMID- 6250423 TI - Role of the raccoon in the transmission of pseudorabies: a field and laboratory investigation. AB - Serum samples were collected from 42 raccoons trapped in a pseudorabies enzootic area of Missouri. All samples were negative for neutralizing antibodies to pseudorabies virus (PRV). Raccoons were orally exposed with one of four dose levels of PRV. The raccoons were found to be susceptible to moderately large doses of PRV tissue culture infective dose (10(4) - 10(5) TCID50). All raccoons given 10(3) TCID50 of PRV survived and did not develop clinical signs. The PRV was consistently isolated from tonsillar swabs collected from raccoons that died after exposure. The PRV was also isolated from the brain, tonsils, lungs, and salivary glands of raccoons that died. It was isolated from samples of the brain and tonsils collected from a raccoon 5 days after death. Neutralizing antibodies to PRV could not be detected in the serum of raccoons that survived PRV exposure. Tonsillar swabs and tissue samples collected from these raccoons were free of PRV. The results indicated that the raccoon may serve as a short-term reservoir for PRV, but it is unlikely to have an ipizootiologic role as a long-term, subclinical carrier of the virus. PMID- 6250424 TI - Horizontal transmission of a pancreas-passaged avian encephalomyelitis virus in chicks. AB - Pancreas-passaged avian encephalomyelitis (AE) virus was transmitted horizontally in a group of 40 (1-day-old) chicks within 3 weeks after they were intermingled with two orally infected 1-day-old chicks. Viral antigen was detected in the pancreas of these contact-exposed chicks. After 5 weeks, contact-exposed chicks developed high titers against AE virus, but the chicks did not develop clinical signs of AE. The passaged virus could not be recovered from feces of six immunized chicks. PMID- 6250425 TI - Evaluation of a hemolysis-in-gel test for detection and quantitation of antibodies to bluetongue virus. AB - A hemolysis-in-gel (HIG) test was developed to detect and quantitate antibody to bluetongue virus (BTV). The HIG test was sensitive and accurate when applied to sera from sheep and cattle infected with BTV. Sensitized sheep RBC were prepared by adsorption of partly purified BTV to the cells. Regression analysis of data showed a linear relationship between the diameter of the hemolytic zone and the log of the antibody concentration. The HIG test did not differentiate among antiodies to four serotypes of BTV, but did differentiate between antibody of BTV and antibody to epizootic hemorrhagic disease virus. PMID- 6250426 TI - Disseminated intravascular coagulation in experimentally induced feline infectious peritonitis. AB - Disseminated intravascular coagulation was induced in kittens by intraperitoneal inoculation of feline infectious peritonitis virus (FIPV). Kittens seronegative to FIPV survived significantly (P less than 0.05) longer than those seropositive to FIPV. Pyrexia, anemia, icterus, hyperbilirubinemia, and elevated concentrations of liver-specific enzymes were detected in the inoculated cats. Lesions induced included disseminated fibrinonecrotic and pyogranulomatous inflammation, hepatic necrosis, and widespread phlebitis and thrombosis. Localization of FIP viral antigen and immunoglobulin G was demonstrated in foci of heptic necrosis by immunofluorescence miroscopy. Lymphopenia, thrombocytopenia, hyperfibrinogenemia, and increased quantities of fibrin fibrinogen degradation products were present in cats after the onset of clinical illness. Depression of factor VII, VIII, IX, X, XI, and XII plasma activities and prolongation of prothrombin and partial thromboplastin times also developed in infected cats. The accelerated onset of clinical disease and mortality in seropositive kittens vs seronegative kittens and the association of virus and antibody in multiple foci of hepatic necrosis suggest an immune-mediated component is involved in the pathogenesis of this disease. PMID- 6250427 TI - Immunofluorescent and electron microscopic studies of feline small intestinal organ cultures infected with feline infectious peritonitis virus. AB - The pathogenesis, morphology, and morphogenesis of feline infectious peritonitis virus were studied in feline small intestinal organ cultures. Characteristic coronaviruses were demonstrated by electron microscopy in the extracellular organ culture fluid taken at 1 through 12, 15, 22, 31, and 43 days after the cultures were inoculated. Viral particles had a mean diameter of 94 nm. Numerous petal shaped projections approximately 15 nm long were seen on the envelopes. Specific immunofluorescence was detected in the absorptive epithelial cells of villi of small intestinal organ cultures at 1 through 12 days after they were inoculated. By electron microscopy, coronavirus particles were observed entirely in the cytoplasm of the infected columnar epithelial cells of villi with no apparent nuclear involvement. Thin sections of the villous epithelium of small intestinal organ cultures showed a number of ultrastructural alterations, and morphogenesis of feline infectious peritonitis virus in the absorptive epithelial cells of villi was consistent with that for other known human animal coronaviruses. PMID- 6250428 TI - Semen changes in boars after experimental infection with pseudorabies virus. AB - Two groups of adult boars were inoculated with a field strain of pseudorabies virus (PRV) by intranasal droplet; one group was given 5 x 10(5) median tissue culture infective doses (TCID50), and the other, 5 x 10(6) TCID50. (A third group was maintained as controls.) Ejaculates were examined twice a week for volume, sperm numbers, sperm morphology, and presence of PRV. Severe clinical disease with fever followed administration of the larger virus dose. Death (one boar), testicular degeneration, and transient elevation in spermatozoa with proximal cytoplasmic droplets were seen in different members of this group. The smaller dose resulted in seroconversion, but did not produce signs of disease. In this group, volume, sperm numbers, and sperm morphology did not decline when compared with base-line values or data of control animals. The virus was not isolated from semen. Effects of PRV infection on semen quality in boars seem to be related to the associated clinical signs of systemic disease. PMID- 6250429 TI - Characterization of immunoglobulin A antibody in serum of swine inoculated with transmissible gastroenteritis virus. AB - Sera and contents of the small intestine from swine inoculated with transmissible gastroenteritis (TGE) virus were examined for immunoglobulin (Ig) A antibody responses by the radioimmunoprecipitation test with antiporcine IgA serum. When swine were orally inoculated with virulent virus, IgA antibody activity was detected in the contents of the small intestine and in serum from postinoculation days 7 to 56. However, IgA antibody activity was not detected in the contents of the small intestine or serum in swine inoculated IM with attenuated virus. The Ig class of serum of swine inoculated with TGE virus was examined by gel filtration chromatography. When swine were orally inoculated with virulent virus, neutralizing antibody was always detected from both fractions of IgA and IgG Neutralizing antibody ws detected only from the IgG fraction in the serum of swine inoculated IM with attenuated virus. The molecular size of serum IgA antibody was determined by sucrose density gradient centrifugation. The titer of this antibody was the highest at a position between 10.9S- and 7S-marker protein. The antibody consisted almost exclusively of dimers. It appeared that serum IgA antibody always originated from the lymphoid tissue of the intestinal tract. This antibody was regarded as an indicator of active immunity of TGE virus. PMID- 6250430 TI - Effect of neonatal thymectomy on pathogenesis of herpesvirus of turkeys in chickens. AB - Effect of immunosuppression on pathogenicity of herpesvirus of turkeys (HVT) in chickens was studied. In three experiments, newly hatched chickens of two genetic strains were surgically thymectmized and gamma-irradiated and then exposed to HVT. Lymphoid cells of thymectomized-irradiated chickens had reduced in vitro mitogenic response; this result indicated that the immunosuppressive regimen caused suppression of T cell function. The immunosuppressed chickens had more circulating HVT and had a slightly higher frequency of microsocpic lesions in peripheral nerves than the intact control chickens, although the intensity of lymphoproliferation remained very mild and no gross lesions or clinical disease was noted during the 5-week observation period. The absence of significant lesion development in an immunosuppressed host indicated that pathogenic potentials of HVT may be limited. PMID- 6250431 TI - Electron microscopic identification and subsequent isolation of a rotavirus from a dog with fatal neonatal diarrhea. AB - Negative contrast electron microscopic examination of intestinal contents from a 3-day-old pup with fatal diarrhea exhibited numerous rotavirus-like particles. Rotavirus was subsequently recovered, using MDCK cells, and was carried through 11 sub-passages; rotavirus-like particles were identified in each passage by negative contrast electron microscopic examination. Experimental inoculation of two 6-month-old Beagle dogs with purified intestinal contents did not result in clinical signs or virus shedding. PMID- 6250432 TI - Hemagglutination by canine parvovirus: serologic studies and diagnostic applications. AB - Conditions for canine parvoviral hemagglutination (HA) and hemagglutination inhibition (HI) reactions were defined. The HA phenomena were used to differentiate canine parvovirus (CPV) from feline panleukopenia virus (FPV), mink enteritis virus (MEV), and minute virus of canines. Serologic comparisons of the CPV, FPV, and MEV by HA-HI and serum-neutralization tests indicated that CPV, FPV, and MEV were antigenically similar but were different from minute virus of canines. Diagnostic application of HA tests to fecal samples from acute cases of enteritis was discussed. Combinating HA tests with HI tests on fecal samples provided a rapid and specific diagnostic method for CPV infection. Secular seroprevalence studies indicated the emergence of CPV infeciton in the United States dog population-at-large in 1978. PMID- 6250433 TI - Effect of paraquat on serum angiotensin converting enzyme. AB - Intraperitoneal administration of paraquat to mice produced a linear dose response increase (20 to 50 mg/kg of body weight) in serum angiotensin converting enzyme (ACE). The peak increase (31%) in ACE occurred after 50 mg/kg of paraquat and began at approximately 4 h. ACE was still significantly elevated 8 h after the administration of paraquat, but it began to return to normal 24 h later. Although serum ACE increased during the first 5 h after the administration of paraquat, lung ACE decreased. The enzyme that we measured in mouse serum was inhibited 100% by 10(-7) M of SQ 20881, a known ACE inhibitor. PMID- 6250434 TI - Cytomegalovirus pneumonia in bone marrow transplant recipients: miliary and diffuse patterns. PMID- 6250435 TI - Pseudoinsulinoma syndrome from inadvertent tolazamide ingestion. AB - A 70-year-old woman with rheumatoid arthritis presented with fasting hypoglycemia, inappropriately elevated insulin and C-peptide levels, and negative insulin antibodies, all compatible with the diagnosis of an insulinoma. However, results of a 72-hour fast were subsequently negative. Medication identification revealed that the patient had been taking tolazamide (Tolinase; The Upjohn Company, Kalamazoo, Michigan) instead of tolmetin (Tolectin; McNeil Laboratories, Inc., Fort Washington, Pennsylvania). PMID- 6250436 TI - Herpes zoster in patients with small-cell carcinoma of the lung receiving combined modality treatment. AB - Herpes zoster, a rare complication in patients with solid tumours, was observed in 13 of 161 (8.1%) patients with small-cell anaplastic carcinoma of the lung treated in a prospective combined modality therapy trial. Induction therapy consisted of three courses of cyclophosphamide, doxorubicin, and vincristine, followed by thoracic radiation. Maintenance chemotherapy with oral lomustine, procarbazine, and methotrexate was given for 1 year. Most herpes zoster cases (11) occurred while patients were on maintenance chemotherapy. Three patients developed nonfatal disseminated herpes zoster and one, postherpetic neuralgia. Herpes zoster may be a relatively frequent complication of prolonged aggressive treatment of small-cell carcinoma of the lung. PMID- 6250437 TI - Trifluoperazine reversal of secretory diarrhea in pancreatic cholera. AB - Diarrhea in a patient with pancreatic cholera syndrome caused by a vasoactive intestinal polypeptide producing pancreatic islet-cell carcinoma responded rapidly and dramatically to the phenothiazine trifluoperazine. Treatment with intravenous somatostatin decreased the plasma vasoactive intestinal polypeptide level without changing the diarrhea. The chemotherapeutic agent chlorozotocin, the 2-chloroethyl analogue of streptozocin, caused a decrease in plasma vasoactive intestinal polypeptide but caused significant renal toxicity with proteinuria. PMID- 6250438 TI - [Malignant chemodectoma of the vagus. One case (author's transl)]. AB - The authors report a case of malignant chemodectoma of the Xth cranial nerve, presenting with a right cervical swelling in a 68-year-old woman, with cervical lymphatic invasion. It was treated by surgical excision complemented by irradiation. PMID- 6250440 TI - Metabolism of proline and the hydroxyprolines. PMID- 6250439 TI - [Radiologic methods of nasopharyngeal angiofibroma diagnosis (author's transl)]. PMID- 6250441 TI - Collagenases. PMID- 6250442 TI - Proteins containing 4Fe-4S clusters: an overview. PMID- 6250443 TI - Integrated genomes of animal viruses. PMID- 6250444 TI - b-Type cytochromes. PMID- 6250445 TI - Discontinuous DNA replication. PMID- 6250446 TI - Enzymes of glycerolipid synthesis in eukaryotes. PMID- 6250447 TI - Calmodulin. PMID- 6250448 TI - Replication of eukaryotic chromosomes: a close-up of the replication fork. PMID- 6250449 TI - Active oxygen species and the functions of phagocytic leukocytes. PMID- 6250450 TI - Enzyme-catalyzed phosphoryl transfer reactions. PMID- 6250451 TI - Mechanisms of gastric H+ and Cl- transport. PMID- 6250452 TI - Humoral control of the pulmonary circulation. PMID- 6250453 TI - Co- and counter-transport mechanisms in cell membranes. PMID- 6250454 TI - Phosphorylation of the myofibrillar proteins. PMID- 6250455 TI - Neuroeffector mechanisms. PMID- 6250456 TI - Biophysical analysis of the function of receptors. PMID- 6250457 TI - Mechanism of action of prolactin in the control of mammary gland function. PMID- 6250459 TI - [Isolation and physicochemical study of the components of the new antibacterial antibiotic 2562]. AB - An antibacterial antibiotic complex consisting of 2 components designated as 2562 A and 2562 B is produced by Streptomyces griseovarabilis. The antibiotic was isolated from the mycelium and purified chromatographically on a column with aqueous silicic acid. The study of the components showed that component 2562 A was chlorbiocin, while component 2562 B differed from the known antibiotics of this group. Physicochemical assays demonstrated that component 2562 B differed from chlorbiocin by the absence of the methyl group in pyrrol, which is probably attached to sugar at beta-position. It was found that component 2562 B is a new representative of the antibiotic cumero-glycoside group. PMID- 6250460 TI - [Structure of carminomycins II and III]. AB - Carminomycins II and III, the main components of the carminomycin complex were isolated in pure state. Their crystalline exalates and acetate of cardminomycin II were prepared. The PMR spectra of both carminomycins and the 13C-NMR spectra of the oxalates were obtained. The molecular weights of the antibiotics were determined by mass-spectrometry. On the basis of the PMR spectra it was shown that carminomycins II and III had similar structures and differed in the stereoisomerism of the nitrogen-free fragment linked to the amino sugar. This was confirmed by the 13C-NMR spectra. The above fragment (C7H15O3) is analogous to the fragment of baumycins A1 and A2 described earlier. PMID- 6250458 TI - Nucleic acid complexing compounds. PMID- 6250461 TI - [Minor components from the carminomycin complex]. AB - Three components differing by their properties from the carminomycins described earlier were isolated from the carminomycin complex. Comparison of the IR and UV spectra, as well as chromatographic and physicochemical properties of 2 of them showed that they were dihydrocarminomycin and its aglycone or dihydrocarminomycinone, which was prepared earlier by synthesis. The third component was a chromophore belonging to 1,4,6-trihydroxyanthraquinone. Investigation of its IR spectrum, physicochemica properties and PMR spectrum showed it to be carboxymethylethylcarminomycinone identical to epsilon rodomycinone. The data were confirmed by 13C-NMR spectrometry. PMID- 6250462 TI - [Permeability of an actinomycoma for ristomycin (experimental studies)]. AB - In vitro studies showed that ristomycin was the most active against actinomycetes causing actinomycosis as compared to benzylpenicillin, ampicillin, methicillin and lincomycin. The growth of the test microbes was inhibited by ristomycin in concentrations of 61--122 mg/ml. Since ristomycin was the most active against actinomycetes, its levels in the blood, parenchymatous organs, capsule and pus of actinomycomas of 5 rabbits infected wtih actino nycosis in the submaxillary area were determined. In the control healthy rabbit, the ristomycin levels were determined in the blood and organs. Ristomycin was administered intravenously in a single dose of 7000 mg/kg. Its concentrations in the animals were determined in 2.5 hours. The results of the experiments showed that ristomycin penetrated in therapeutic concentrations into the connective tissue capsule of actinomycoma. As for the other antibiotics tested earlier, they failed to penetrate this barrier. In 3 infected rabbits, ristomycin penetrated even the pus contained in actinomycoma. Ristomycin provides therapeutic concentrations in the disease focus and may produce a satisfactory therapeutic effect in treatment of actinomycosis. PMID- 6250463 TI - [Structure of the carbohydrate moiety of carminomycins II and III]. AB - Saccharides II and III were obtained on catalytic hydrogenolysis of carminomycins II and III. The saccharides contained daunosamine and a nitrogen-free fragment of unknown structure. Crotonic aldehyde in the form of 2,4-dinitrophenylhydrazone and 1,2-propylenglycol in the form of 3,5-dinitrobenzoate were isolated on acid hydrolysis of the saccharides. The study on the chemical and spectral properties (PMR-spectra) of the saccharides, their N,O-acetates and hydrolysis products suggested the structure of th carbohydrate moiety of carminomycins II and III as a disaccharide of daunosamine and acyclic semiacetal of 2,4-desoxytetrose. PMID- 6250464 TI - [Ability of vancomycin-group antibiotics to induce or to inhibit thrombocyte agglutination]. AB - The effect of 4 vancomycin antibiotics on factor VIII-dependent agglutination of thrombocytes was studied. Significant similarity, both quantitative and qualitative, between ristocetin and ristomycin was found. In this connection ristomycin may be used for determination of the so-called ristocetin cofactor. Actinoidin and vancomycin inhibited agglutination of platelets induced by ristocetin or ristomycin in platelet-enriched plasma with citrate or EDTA the same as in the system contaning platelets treated with formalin and did not inhibit agglutination induced by the bovine factor VIII. The 4 antibiotics induced precipitation of the plasma protein. Vancomycin was most active and actinoidin ws lest active in this respect. Ristocetin and ristomycin also possessed such capacity, the effect of the latter being higher. Actinoidin and vancomycin did not prevent the immediate effect of light absorption increasing due to addition of ristocetin or ristomycin to fixed platelets in concentrations completely inhibiting agglutination of platelets in the presence of the protein cofactor. Inhibition of this direct effect of ristocetin and ristomycin was observd only at higher concentrations, which indicated that this effect was not probably associated with agglutination. The results of the study on various ristomycin derivatives showed that methylated carboxylic groups and free hydroxyls of phenol may play the main role in ristomycin binding with the thrombocytic membrane and/or protein cofactor. PMID- 6250465 TI - Hydrolysis of Cefotaxime by a beta-lactamase from Bacteroides fragilis. AB - A beta-lactamase isolated from a strain of Bacteroides fragilis subsp. fragilis possessed hydrolytic activity toward cefotaxime. This antibiotic was degraded to a lower extent than was cephalothin, cephaloridine, and cefamandole, whereas cefoxitin remained unaffected by the enzyme. Kinetic parameters Vmax and Km for cefotaxime were calculated at 0.172 mumol/min and 1.1 X 10(-2) mM, respectively. PMID- 6250466 TI - Antiviral activity of tunicamycin on herpes simplex virus. AB - Tunicamycin (0.5 microgram/ml) significantly lowers (2 to 3 log10) the infectious yield of herpes simplex virus type 1 grown in chicken embryo fibroblasts and in BSC1 cells. Although virus particles are formed and the synthesis of the viral deoxyribonucleic acid is only partially affected by the antibiotic, the glycosylation of herpesvirus glycopeptides is amost completely inhibited. The morphology of virus particles made in the presence of tunicamycin is similar to that of intact virus particles, as demonstrated by electron microscopy. This suggests that the absence of the carbohydrate side-chain from the viral glycopeptides does not affect the overall integrity of the virion but decreases very significantly the infectivity of these particles. PMID- 6250467 TI - Antiherpesviral activity and inhibitory action on cell growth of 5-alkenyl derivatives of 1-beta D-arabinofuranosyluracil. AB - Antiherpesviral activity of 5-vinyl-1-beta-D-arabinofuranosyluracil was as high as that of 1-beta-D-arabinofuranosylthymine, whereas the former was less inhibitory to cell growth than the latter. 5-Propenyl- and 5-butenyl-1-beta-D arabinofuranosyluracil were less active than 5-vinyl-1-beta-D arabinofuranosyluracil. PMID- 6250468 TI - Inhibition of herpes simplex virus multiplication by the pokeweed antiviral protein. AB - The pokeweed antiviral protein inhibited the multiplication of herpes simplex virus type 1 in cell culture. The extent of antiviral activity was proportional to the length of time that the antiviral protein was present postinfection. The results demonstrate that the continued presence of the pokeweed antiviral protein is necessary for the maximum inhibition of virus yields. PMID- 6250470 TI - In vitro activities of moxalactam and cefotaxime against aerobic gram-negative bacilli. AB - The in vitro activities of two new beta-lactam antibiotics, moxalactam disodium (LY 127935) and cefotaxime (HR-756), were compared with cefoxitin, cefamandole, cefuroxime, cephalothin, and, in some instances, carbenicillin, gentamicin, and amikacin against aerobic gram-negative bacilli. Test isolates included normally cephalosporin-resistant members of the Enterobacteriaceae and Pseudomonas spp. and a variety of nonfermentative or oxidase-positive bacteria. Both moxalactam and cefotaxime demonstrated impressive in vitro activities against both groups of microorganisms. The two new drugs were clearly more active than any of the other beta-lactam antibiotics against species of Escherichia, Citrobacter, Enterobacter, Klebsiella, Proteus, Providencia, Pseudomonas, and Serratia. An additive or synergistic effect could also be demonstrated with the majority of Pseudomonas and Serratia isolates when either moxalactam or defotaxime was combined with amikacin. PMID- 6250469 TI - In vitro and in vivo effects of the antimycotic drug ketoconazole on sterol synthesis. AB - Ketoconazole, an orally active antimycotic drug, is a potent inhibitor of ergosterol biosynthesis in Candida albicans when added to culture media which support yeast or mycelial growth or to cultures containing outgrown mycelium. This inhibition coincides with accumulation of sterols with a methyl group at C 14 and can thus be attributed to an interference with one of the reactions involved in the removal of the 14 alpha-methyl group of lanosterol. When administered to rats infected with C. albicans, ketocanazole also inhibits fungal synthesis of ergosterol. A six-times-higher dose is required to effect cholesterol synthesis by rat liver. PMID- 6250471 TI - In vitro activity of mecillinam against anaerobic bacteria. AB - A microtiter broth dilution method was employed to determine the in vitro activity of mecillinam against 201 recent clinical isolates of anaerobic bacteria. Both the anaerobic gram-positive and anaerobic gram-negative bacilli displayed a wide range of minimal inhibitory concentrations of mecillinam; most strains were resistant to the antibiotic. The anaerobic cocci exhibited a narrower range of minimal inhibitory concentrations than were observed with other anaerobes, but also exhibited mecillinam resistance. As a single drug, mecillinam does not appear to be an effective antimicrobial agent against anaerobic bacteria. PMID- 6250472 TI - Survival of human enteroviruses in the Hawaiian ocean environment: evidence for virus-inactivating microorganisms. AB - The stability of certain human enteroviruses in the Hawaiian ocean environment was examined. The present data indicated that the time for 90% reduction of poliovirus type 1 at 24 +/- 1 degree C in seawater samples obtained from different sites in Hawaii ranged from 24 to 48 h, and complete inactivation occurred within 72 to 96 h. The accumulated evidence also strongly indicated that a virus-inactivating agent(s) of a microbiological nature was present in both clean and sewage-polluted seawaters, but not in fresh, mountain stream waters. The antiviral activity was lost when the seawater samples were subjected to boiling, autoclaving, or filtration through a 0.22- or 0.45-micrometer, but not a 1.0-micrometer, membrane filter. That the antiviral activity of the seawater was related to the growth activities of microorganisms was corroborated by the observed effects of added nutrients, a lower temperature of incubation, and the presence of certain antibiotics. Other enteric viruses, such as coxsackie virus B 4 and echo virus-7, were also shown to be similarly inactivated in seawater. PMID- 6250473 TI - Improved method for purification of enterotoxin from Clostridium perfringens type A. AB - The purification procedure of Clostridium perfringens type A enterotoxin has been improved. The cell sonic extract was precipitated twice with ammonium sulfate, first 40% saturated to concentrate the enterotoxin and then 15% saturated. The two precipitations were followed by gel filtration on Sephadex G-100. The enterotoxin appeared to be homogeneous on 7% polyacrylamide gel electrophoresis after this three-step purification procedure, with a recovery of 56% and a 12.3 fold purification. The solubility properties at different pH values, temperatures, and ammonium sulfate concentrations are also given as basis for the purification procedure. PMID- 6250475 TI - Effects of wastewater sludge and its detergents on the stability of rotavirus. AB - Wastewater sludge reduced the heat required to inactivate rotavirus SA-11, and ionic detergents were identified as the sludge components responsible for this effect. A similar result was found previously with reovirus (R. L. Ward and C. S. Ashley, Appl. Environ. Microbiol 36:889-897, 1978). The quantitative effects of individual ionic detergents on rotavirus and reovirus were very different, and rotavirus was found to be extremely sensitive to several of these detergents. However, neither virus was destabilized by nonionic detergents. On the contrary, rotavirus was stabilized by a nonionic detergent against the potent destabilizing effects of the ionic detergent sodium dodecyl sulfate. The destabilizing effects of both cationic and anionic detergents on rotavirus were greatly altered by changes in the pH of the medium. PMID- 6250474 TI - Comparative study on the mechanisms of rotavirus inactivation by sodium dodecyl sulfate and ethylenediaminetetraacetate. AB - This report describes a comparative study on the effects of the anionic detergent sodium dodecyl sulfate and the chelating agent ethylenediaminetetraacetate on purified rotavirus SA-11 particles. Both chemicals readily inactivated rotavirus at quite low concentrations and under very mild conditions. In addition, both agents modified the viral capsid and prevented the adsorption of inactivated virions to cells. Capsid damage by ethylenediaminetetraacetate caused a shift in the densities of rotavirions from about 1.35 to about 1.37 g/ml and a reduction in their sedimentation coefficients. Sodium dodecyl sulfate, on the other hand, did not detectably alter either of these physical properties of rotavirions. Both agents caused some alteration of the isoelectric points of the virions. Finally, analysis of rotavirus proteins showed that ethylenediaminetetraacetate caused the loss of two protein peaks from the electrophoretic pattern of virions but sodium dodecyl sulfate caused the loss of only one of these same protein peaks. PMID- 6250476 TI - Isolation and identification of pathogenic microorganisms at wastewater-irrigated fields: ratios in air and wastewater. AB - Samples of air and corresponding wastewater samples were taken at wastewater spray-irrigated fields. The concentrations of salmonellae and enteroviruses present in these samples were determined and compared with those of coliforms, and the ratios between them were calculated. The most common Salmonella serotype in the air was Salmonella ohio, whereas in the wastewater, Salmonella anatum was the most common. Enteroviruses isolated and identified were poliovirus, echovirus, and coxsackievirus type B. From the ratios of salmonellas to coliforms and enteroviruses to coliforms in the air, as compared to these ratios in the wastewater, it was concluded that the suitability of coliforms as an indication of airborne contamination caused by spray irrigation is questionable. PMID- 6250477 TI - Purification of glycoside hydrolases from Bacteroides fragilis. AB - Six glycoside hydrolases in the culture medium of Bacteroides fragilis--alpha glucosidase, beta-glucosidase, alpha-galactosidase, beta-galactosidase, beta-N acetylglucosaminidase, and alpha-L-fucosidase-were systematically purified by ammonium sulfate precipitation, gel filtration chromatography, and density gradient isoelectric focusing. The isoelectric focusing resolved the glycosidases into distinct, well-separated fractions and revealed three differently charged forms of beta-N-acetylglucosaminidase and of alpha-L-fucosidase. Furthermore, alpha-glucosidase and beta-N-acetylglucosaminidase were shown to possess dual affinities for the respective galactoside substrates, and beta-galactosidase also hydrolyzed beta-D-fucoside. alpha-Glucosidase was purified to homogeneity, as indicated by a thin-layer isoelectric focusing zymogram technique. The glycosidases, with exception of beta-glucosidase and the acid alpha-L-fucosidase, were each separated from other glycosidic activities to 99%. The molecular weights varied between 58,000 and 125,000. The pH optima ranged from 4.8 to 6.9. PMID- 6250478 TI - Interactions and survival of enteric viruses in soil materials. AB - There were marked differences in the abilities of eight different soil materials to remove and retain viruses from settled sewage, but for each soil material the behavior of two different viruses, poliovirus type 1 and reovirus type 3, was often similar. Virus adsorption to soil materials was rapid, the majority occurring within 15 min. Clayey materials efficiently adsorbed both viruses from wastewater over a range of pH and total dissolved solids levels. Sands and organic soil materials were comparatively poor adsorbents, but in some cases their ability to adsorb viruses increased at low pH and with the addition of total dissolved solids or divalent cations. Viruses in suspensions of soil material in settled sewage survived for considerable time periods, despite microbial activity. In some cases virus survival was prolonged in suspensions of soil materials compared to soil-free controls. Although sandy and organic soil materials were poor virus adsorbents when suspended in wastewater, they gave >/=95% virus removal from intermittently applied wastewater as unsaturated, 10-cm deep columns. However, considerable quantities of the retained viruses were washed from the columns by simulated rainfall. Under the same conditions, clayey soil material removed >/=99.9995% of the viruses from applied wastewater, and none were washed from the columns by simulated rainfall. PMID- 6250480 TI - Specific binding protein for 1,25-dihydroxyvitamin D3 in bovine mammary gland. PMID- 6250479 TI - The nature of the axial ligands of spinach cytochrome. PMID- 6250481 TI - Epidermal growth factor-urogastrone receptor: selective alteration in simian virus 40 transformed mouse fibroblasts. PMID- 6250482 TI - Putative superoxide dismutase activity of iron-EDTA: a reexamination. PMID- 6250483 TI - Lysosomal membrane adenosine triphosphatase; solubilization and partial characterization. PMID- 6250484 TI - Biogenesis of mitochondria: a temperature sensitivity mutation affecting the mitochondrially synthesized var1 protein of Saccharomyces cerevisiae. PMID- 6250485 TI - Epinephrine-stimulated phosphorylation of pyruvate kinase in hepatocytes. PMID- 6250486 TI - Regeneration of reduced-denatured seminal ribonuclease: effect of modification at cysteines 31 and 32. PMID- 6250487 TI - The degradation of adrenocorticotrophic hormone-(1-4) by mouse brain cytosol. PMID- 6250488 TI - The reaction of red blood cell catalase with perchlorate. PMID- 6250489 TI - Production of superoxide anions in Paracoccus denitrificans. PMID- 6250490 TI - Storage and secretion of beta-endorphin and related peptides by mouse pituitary tumor cells: regulation by glucocorticoids. PMID- 6250491 TI - A partial characterization of the cyclic nucleotide phosphodiesterases of Drosophila melanogaster. PMID- 6250492 TI - (Na+,K+)-ATPase of mammalian brain: differential effects on cation affinities of phosphorylation by ATP and acetylphosphate. PMID- 6250494 TI - The phosphorylation potentials generated by respiring Ehrlich ascites tumor mitochondria. PMID- 6250493 TI - Reconstitution and characterization of a sodium-stimulated active aminoisobutyric acid transport system derived from partially purified plasma membranes from mouse fibroblasts transformed by simian virus 40: comparison of reconstituted vesicles with native membrane vesicles. PMID- 6250495 TI - Liver glycogen synthase phosphatase and phosphorylase phosphatase activities in vitro following glucose and glucagon administration. PMID- 6250496 TI - The captopril-induced eruption. A possible mechanism: cutaneous kinin potentiation. AB - Captopril, an orally active dipeptidyl-carboxypeptidase inhibitor, is a promising new antihypertensive agent. Cutaneous reactions are the most common side effects of this therapy. The data from 15 previous cases and seven new ones are reviewed. The cutaneous eruptions appear to be pharmacologic. In nature, occurring mostly at higher dosage schedules and resolving at lower dosage levels. Historical data, the results of skin tests, and the known pharmacology of captpril suggest that these captopril-induced eruptions may be the result of potentiation of kinin mediated cutaneous reactions. PMID- 6250497 TI - Noninvasive breast carcinoma: results of a national survey by the American College of Surgeons. AB - This study evaluates the data of noninvasive (in situ) lobular (ISLC) and ductal (ISDC) carcinoma, collected from 498 hospitals in a National Breast Cancer Survey, carried out by the American College of Surgeons in 1978. ISLC and ISDC were identified in 323 (3.2%) of 10,054 female patients with lobular and ductal carcinoma, of the total of 23,972 patients with histologically proven breast cancer surveyed (1.4%). The frequency of ISLC was significantly higher (18.5%) than ISDC (2.1%) suggesting a less agressive nature of ISLC, with a slower progression to invasion than ISDC. There was a different age distribution of ISLC and ISDC: about 80% of ISLC and 50% of ISDC were diagnosed in patients who were less than 54 years old, and the incidence showed a marked decrease in the older age groups in ISLC, whereas the incidence remained high in the following decade in ISDC. In this series there was a distinctly better five-year cure rate in the patients with ISLC (83.5%) than in the patients with ISDC (68.8%), in spite of the fact that radical surgery was performed more frequently in ISDC (67.8%) than ISLC (36.3%). The recurrence rate was five times higher (10.5%) in ISDC than in ISLC (2.5%). In black patients the recurrence rate (21.3%) was significantly higher in ISDC than in white patients (9.3%). In the present study there were no statistically significant differences in the five-year cure and recurrence rate in patients with noninvasive carcinoma, treated by more conservative procedures (72.9% and 8.5%) and those treated by more extensive surgeries (76.2% and 7.7%). The results of this study suggests that the biologic behavior of ISLC and ISDC may be different with regard to their propensity to invade and their overall prognosis. In contrast, the infiltrative form of lobular and ductal carcinoma, were found to have the same prognosis, regardless of the type of operative procedure performed. PMID- 6250498 TI - Effects of thyroid hormone deficiency on pre- and postsynaptic noradrenergic mechanisms in the rat cerebral cortex. AB - Thyroid hormones are known to influence the noradrenergic neurotransmission in several peripheral organs. In order to find out whether similar changes exist in the central nervous system, we investigated adrenoceptor-mediated responses in the rat brain cortex during propylthiouracil-induced hypothyroidism. In contrast to unchanged basal cAMP levels, the cAMP accumulation following (-)noradrenaline incubation (3 X 10(-6)--3 X 10(-5) M) was significantly reduced in brain slices from hypothyroid animals. The difference between controls and propylthiouracil fed rats became more pronounced when (-) isoprenaline (3 X 10(-6)--3 X 10(-5) M) was used for selective stimulation of beta-adrenoceptors. Since the cAMP increase mediated via alpha-adrenoceptors was not affected, it may be concluded that thyroid hormone deficiency only impairs the beta-adrenergic transmission. Phosphodiesterase activity remained unaltered suggesting that thyroid hormones influence the beta-adrenoceptors or the adenylate cyclase coupled to it. The sensitivity of presynaptic alpha-adrenoceptors modulating the release of noradrenaline was evaluated using occipital cortical slices preincubated in 3H noradrenaline. Clonidine inhibited whereas phentolamine enhanced the 3H-overflow induced by electrical stimulation in a dose-dependent manner. No differences could be detected between control- and propylthiouracil-treated animals. Thus presynaptic alpha-adrenoceptors are not affected by hypothyroidism. PMID- 6250499 TI - alpha-methyldopa reduces locomotor activity in rats via its metabolite, alpha methylnorepinephrine, acting on alpha 2-adrenoceptors. AB - The decrease in locomotor activity in rats caused by alpha-methyldopa (alpha-MD), 400 mg/kg p.o. was antagonized by treatment with yohimbine, a selective antagonist of alpha 2-adrenoceptors. Effective doses of yohimbine ranged from 0.25--2.0 mg/kg s.c., whereas yohimbine at 0.125 mg/kg did not significantly affect the decrease in locomotor activity caused by alpha-MD. Similar results were obtained in studies on the interaction between clonidine injected intracisternally and various doses of yohimbine given s.c., except that the higher doses of yohimbine completely blocked the depression of locomotor activity caused by clonidine, but not by alpha-MD. The depression of motor activity following alpha-MD was not offset by prazosin, a preferential alpha 1-antagonist. At the same doses that failed to alter the action of alpha-MD, prazosin was effective in antagonizing the increase in motor activity resulting from intracisternally injected methoxamine, a selective agonist, at alpha 1-receptors. Treatment with FLA-63, using a regimen that was shown to inhibit dopamine-beta hydroxylase in brain, caused a diminution in the ability of alpha-MD to depress locomotor activity. These findings indicate that alpha-MD reduces locomotor activity in the rat at least in part via the formation of alpha methylnorepinephrine which acts on alpha 2-adrenoceptors. PMID- 6250500 TI - An apparent preferential antagonism by practolol of the positive inotropic responses of guinea-pig isolated atria to isoprenaline. AB - The positive inotropic response of guinea-pig isolated atria to isoprenaline was antagonized to a greater extent than the positive chronotropic response, when measured at 38 degrees C as the reduction of the responses to a single concentration of isoprenaline. This method avoided increasing the the concentration of agonist in the presence of practolol and any difference in the proportion metabolized affecting the blockade. This observation was substantiated from the vertical displacement of dose-response curves from four concentrations of isoprenaline added sequentially. No difference between the antagonism of rate and tension was obtained when the antagonism was measured as the horizontal displacement of complete dose-response curves constructed sequentially or cumulatively. The resultant pA2 values from cumulative dose-response curves were identical, indicating that the beta-adrenoceptors subserving these responses are the same. The rate and tension curves were not, however, superimposable; rate lay to the left. By lowering the bath temperature to 30 degrees C they were brought together and the selective antagonism was no longer observed. This phenomenon was therefore attributed to the separation of rate and tension curves at 38 degrees C, the selected concentration of isoprenaline occupying different positions on these curves. PMID- 6250502 TI - Sodium activation of heart (Na+ + K+)-ATPase from normotensive and spontaneously hypertensive rats. AB - The sodium activation of heart (Na+ + K+)-ATPase has been studied in a microsomal fraction prepared from hearts of normotensive and spontaneously hypertensive Wistar rats. The results show that the apparent affinity of the transport enzyme for sodium was lower in hypertensive than in normotensive rats. PMID- 6250501 TI - Differences in pharmacological properties of postjunctional alpha-adrenergic receptors among arteries and veins. PMID- 6250503 TI - Stimulation and inhibition of synaptosome ATPases by noradrenaline. The involvement of cytoplasmic factor. AB - The activity of Na+, K+-ATPase was determined in synaptosomes and in pellets, (containing membranes, mitochondria and vesicles) and cytoplasm prepared from synaptosomes from rat cerebral cortex. The activity of the pellets was more than two fold higher than that of the synaptosomes or of their components and adding back the cytoplasm reduced the activity of the pellets. Noradrenaline did not affect the activity of the pellets but increased that of the synaptosomes in a dose-dependent fashion. It inhibited the activity of the membranes. Results indicate that synaptosomal Na+, K+-ATPase activity is low because of a factor in the cytoplasm and this factor is not present in synaptosome pellets. NA antagonises the activity of the factor. PMID- 6250504 TI - The effect of amino-substitution on the beta-adrenoceptor activity of 4 bromophenylethanolamines. AB - A series of 4-bromophenylethanolamines with a variety of amino substituents has been prepared. A detailed pharmacological evaluation has been made of their beta adrenergic activity to study how the amino substituent may effect the mixed agonist and antagonist action of a phenylethanolamine series. PMID- 6250505 TI - Cyclic nucleotide elevation preceding catecholamine release in isolated dog adrenals. AB - Acetylcholine caused the rapid elevation of cAMP and cGMP levels with a peak within 30 sec in the medulla and in the perfusate preceding catecholamine release in isolated perfused dog adrenal glands. These responses to ACh were completely blocked by hexamethonium plus atropine. A functional role of cyclic nucleotides in catecholamine secretion mechanisms is discussed. PMID- 6250506 TI - Ionophoretic activity of hypoglycemic sulfonylureas. AB - Hypoglycemic sulfonylureas, such as tolbutamide, gliclazide and glipizide, provoked the translocation of Ca from an aqueous medium into or across an organic immiscible phase. The amount of Ca translocated into the organic phase was proportional to the square of the drug concentration, and appeared saturable at high Ca concentration. Non-hypoglycemic sulfonylureas and diazoxide had little or no effect upon Ca translocation. The ionophoretic capacity of the hypoglycemic sulfonylureas was antagonized by suloctidil. Tolbutamide and gliclazide also provoked Na translocation into the organic phase, the amount of Na translocated being proportional to the drug concentration. Gliclazide-mediated Ca translocation was inhibited in a dose-related fashion by increasing concentrations of Na+ or H+. It is proposed that the ionophoretic capacity of hypoglycemic sulfonylureas may participate in their insulinotropic action. PMID- 6250507 TI - Lymphoid hypophysitis with selective adrenocorticotropic hormone deficiency. AB - This report describes a 31-year-old woman with evidences of selective adrenocorticotropic hormone deficiency associated with a remarkable pituitary lesion, lymphoid hypophysitis. Clinical manifestations of secondary hypocortisolism, which first appeared during the immediate postpartum period following normal pregnancy, included progressive weakness and mental aberrations, fasting hypoglycemia, transient hypercalcemia, and striking ECG changes. Sudden death resulted from cardiorespiratory collapse. Microscopic examination of the anterior pituitary disclosed focal fibrosis and extensive lymphocytic infiltrations with a marked reduction of basophils; immunostaining techniques demonstrated a selective loss of corticotropin-secreting cells. The histopathology of the pituitary and its association in this case with lymphoid thyroiditis suggest that selective damage to corticotrophs was due to an autoimmune process. PMID- 6250509 TI - [Effect of pilocarpine on cell proliferation and the concentration of cyclic nucleotides in murine spleen cell preparations]. PMID- 6250508 TI - [Clostridium perfringens infection and necrotising enterocolitis]. AB - During a four year period (1974--1977) 21 infants died as a result of severe necrotising enterocolitis (N.E.C.). In 9 cases, Clostridium perfringens was isolated. When this organism is recovered either from the placenta or from the first meconium and or when the signs of the disease appear within a few days of birth, materno-fetal transmission of the infection may be suspected. The infection occurs most frequently in neonates in whom the gastrointestinal tract was already colonized by Clostridium. PMID- 6250510 TI - Rehabilitation outcome: comparative analysis of different patient types. AB - Postdischarge progress in 11 types of patients was analyzed with regard to eating, dressing, transfers, bladder management, ambulation, cognition, language comprehension and speech, placement (living arrangement), and mortality rates. Of 273 patients admitted, 263 were available for foillow-up, which disclosed that patients with lower bladder management and cognition scores are more likely to be directed into restrictive discharge placements (p < 0.05), and that CVA patients with right and left cerebral hemisphere involvement, cancer patients, and patients with brain stem infarctions make significant postdischarge gains in ADL (p < 0.05). The majority of patients showed continual improvement after discharge, some making significant gains in functional competency. Such program evaluation offers a systematic method for forecasting post-discharge outcome. PMID- 6250511 TI - Variable effect on chromosomes of six herpes simplex virus isolates. PMID- 6250512 TI - Effect of zinc ions, phosphonoacetate, phosphonoformate and violamycin BI on the induction by herpes simplex virus of chromosome abnormalities in cell cultures. PMID- 6250513 TI - Restriction of herpes simplex virus by Ama 1 cells. An analysis of viral macromolecule synthesis. AB - Ama 1 cells, and alpha-amanitin-resistant subline of CHO cells, restricted herpes simplex virus-1 and -2 replication. The infection was characterized by i) induction of typical cytopathology; ii) appearance of all the major virus proteins, glycoproteins and DNA earlier than in HEp-2 cells, followed by shut off of virus macromolecule synthesis; iii) defective maturation of viral particles, i.e. scarce assembly and lack of envelopment. The early shut off of viral DNA and protein synthesis, and the altered glycoprotein pattern may account for herpes simplex virus restriction. PMID- 6250514 TI - Studies on poxvirus infections in irradiated animals. AB - If rabbits were given total body irradiation and infected wih vaccinia virus (strain Elstree) a severe disease developed with a viraemia lasting up to 12 days. The clearance of the virus from the peripheral blood was severely impaired by x-ray doses above 800 R. The attenuated vaccinia virus strain MV did not turn virulent, if it was injected to irradiated rabbits. With caution it can be assumed that live vaccines, containing attenuated viruses, may be given to immunosuppressed persons. Rats are not susceptible to ectromelia-virus (mouse poxvirus); overt clinical sympatoms, however, with a mortality of 30 per cent developed in irradiated rats. This proofs that specific poxviruses can be transferred to another species. As the experimental conditions are unnatural, this may occur only rarely in immunosuppressed persons. After intracerebral infection of Balb-C-mice with low doses of vaccinia virus two types of infection were seen: 1. a severe cytocidal infection of leptomeninges, chorioid plexus and vessels; 2. a noncytocidal, latent infection of glial cells and neurons. Several animals developed a picture resembling experimental allergic encephalomyelitis. It seems that irradiation altered the antigenic conditions of the cytoplasmic membranes in non-cytocidally infected cells. The model might explain some processes in the pathogenesis of demylinating diseases. PMID- 6250515 TI - Electron microscopic studies of herpes simplex virus type 1 infection of macrophages, T- and B-lymphocytes of mice. AB - The course of infection with herpes simplex virus type 1 (HSV-1) in peritoneal macrophages, phytohemagglutinin (PHA-)stimulated (T-)lymphocytes and lipopolysaccharide (LPS-)stimulated (B-)lymphocytes of NMRI-mice was studied by means of electron microscopy. Non-stimulated as well as thioglycolate-stimulated macrophages were investigated; lymphocytes were derived both from HSV-1 sensitized and non-sensitized animals. The morphological characteristics of the abortive infection in macrophages and T-lymphocytes and of the productive infection in B-lymphocytes are described. No differences were observed between stimulated and non-stimulated cells or cells of sensitized and non-sensitized animals. PMID- 6250516 TI - Ribonuclease H levels in herpes simplex virus-infected cells. AB - Two forms of ribonuclease H (RNase H) have been identified both in uninfected and Herpes Simplex virus (HSV-)infected BHK cells. Identical RNase H species were detected in control- as well as in infected cells. RNase H I and II have not been found to be associated both with host cell DNA polymerase alpha and beta and HSV induced DNA polymerase. Infection of BHK cells with HSV type 1 does not lead to a pronounced alteration of RNase H II activity but to an increase (3-fold) of the extractable RNase H I activity. RNase H I activity increases to a maximum between 8-10 hours p.i.; the bulk of HSV-DNA synthesis occurs between 6-8 hours p.i. From these experiments we draw the preliminary conclusion that RNase H I is involved in the degradation of the RNA primer which is covalently linked to newly synthesized HSV-DNA strands. PMID- 6250517 TI - Ultrastructural studies on Maedi-Visna virus. AB - Ultrastructural studies of Maedi-Visna virus (MVV) particles isolated from tissue culture fluids of MVV-infected cells as well as cultured cells infected with MVV were performed. MVV particles aree bounded by an envelope with projections loosely attached to its surface. Virions contain a core (sometimes two or more) of conical or ovoid shape enclosing an electron-dense nucleoid which is much smaller in diameter than the core and which can only be seen in ultrathin sections. A distinct core shell is to be found in most of the ultrasectioned particles. Cores, liberated from the virions by detergent treatment, exhibited the same shape as their enveloped counterparts. Budding structures with crescents underlying the cell membrane without an intermediate space seem to be bordered on their cell side by an electron-dense thin layer. Particles obviously representing intervenig stages of viral maturation showing parts of the crescents at the viral membrane and empty core shells could be found in single cases. PMID- 6250518 TI - [Age and the activity of certain enzymes in developing muscle fibers]. PMID- 6250519 TI - [ultrastructural localization of adenylate cyclase activity in the smooth muscle cells of the wall of the aorta and the kidney]. AB - As the data on estimation of adenylate cyclase activity in the aortic and nephric tissue have demonstrated the product of histochemical reaction is localized in sarcolemmic vesicles of the aortic wall smooth muscle and on the plasmic membrane of the brush border microvilli in the proximal tubules of the kidney. From our knowledge on how some hormones affect the cell via the intracellular mediator cAMP, which is formed from Atp at activation of the adonylate cyclase system, it is possible to suggest that sarcolemmic vesicles of the smooth muscle cells and separate parts in plasmolemma of the brush border of the proximal tubules correspond to the adenylate cyclase system in the receptory zones where the hormones interact with the cell. It is interesting to note topographic coincidence in one ultrastructure--sarcolemmic vesicules--of the adenylate cyclase system and a sarcolemmic area through which calcium ions (the primary regulator of contractility) are excreted at relaxing action of beta-adrenergetics on the smooth muscles. PMID- 6250520 TI - Cyclic guanosine-5'-phosphate and protease secretion from rat submandibular gland in vitro. PMID- 6250522 TI - Physician, heal thyself. PMID- 6250521 TI - Early detection of asymptomatic hereditary chemodectoma with radionuclide scintiangiography. A possibility for family screening and surveillance. AB - A large family with a history of hereditary chemodectoma has been successfully screened by means of radionuclide scintiangiography. This procedure could restrict selective and more invasive roentgenangiography only to those cases in which flow patterns are abnormal. Three asymptomatic cases of chemodectoma were revealed by this method. Early therapeutic measures may now be feasible. We discuss the possibilities for surveillance of these families without causing discomfort to the group involved. PMID- 6250523 TI - Painful conditions of peripheral nerves. AB - A plea is made for the early recognition of the possible development of painful conditions affecting peripheral nerves, since it is believed that the experience of our institution, which is detailed here, confirms that while rehabilitation programmes are of benefit to the patient, successful therapy depends upon prompt institution of prophylactic measures to prevent sensitization to sympathetic outflow. Patients are encouraged to use their hands, and it is considered important that they would understand that their complaints arise from a genuine organic condition. PMID- 6250524 TI - A transmissible chicken tumour associated with reticuloendotheliosis virus infection. AB - Histiocytic lymphosarcomas of the intestine, liver, spleen and sciatic nerve were found at necropsy in a 36-week-old laying hen that was culled from a flock of 1800 birds because of emaciation. Type C particles were observed in ultrathin sections of liver and spleen. The serum of the hen contained reticuloendotheliosis virus (REV) antigen, and antibody against REV, but lacked antibodies reactive with Marek's disease virus or subgroups A and B of Rous sarcoma virus. The tumour was transmitted to chickens using a suspension of the initial tumours. These experimental tumours were then transmitted to further chickens, using cultured spleen cells, viable spleen cells that had been stored frozen, and disrupted spleen cells. The tumours, which developed after incubation periods as short as 2 weeks, were histologically similar to those in the original hen. A few chickens also developed feather abnormalities. The chickens with experimentally transmitted tumours developed antibody against REV and REV antigen was demonstrated in cultured cells from these chickens. The chickens failed to develop antibody against Rous sarcoma virus and only 1 of 29 developed antibody against Marek's disease virus. PMID- 6250525 TI - Isolation of bovine leucosis virus from cattle. PMID- 6250526 TI - Differentiation of equine herpesviruses of type 1. PMID- 6250527 TI - Differentiation of subtypes within equine herpesvirus type 1. PMID- 6250528 TI - A generalised infection of cattle with bovine herpesvirus 2. PMID- 6250529 TI - [Herpesvirus infections in men and animals, problems and combat]. PMID- 6250530 TI - [The rotating aeration (system Fuchs) for treatment of liquid animal and municipal wastes. 9. report: the effect of aerobic treatment of pig slurry containing pseudorabies virus]. PMID- 6250531 TI - [Detection of neutralizing antibodies against avian adenoviruses by a mircotiter cell culture system]. PMID- 6250532 TI - Utilization of membranous lipid substrates by membranous enzymes. Hydrolysis of sphingomyelin in erythrocyte 'ghosts' and liposomes by the membranous sphingomyelinase of chicken erythrocyte 'ghosts'. AB - Incubation at 37 degrees C of haemolysed chicken erythrocytes ('chicken erythrocyte ghosts') resulted in hydrolysis of the membrane sphingomyelin, suggesting an activation of a latent sphingomyelinase during the haemolysis procedure. When this incubation was continued for several hours, the entire sphingomyelin of the erythrocyte 'ghosts' was hydrolysed and membranes were obtained that were devoid of sphingomyelin, but had an active sphingomyelinase. Mixing the latter membranes with human erythrocyte 'ghosts' or positively charged liposomes led to hydrolysis of the sphingomyelin in these two membranes. This suggested that, after haemolysis, the activated sphingomyelinase in the membrane of the chicken erythrocyte 'ghosts' could hydrolyse sphingomyelin in its own membrane ('intramembrane utilization') or adjacent membranes ('intermembrane utilization'). PMID- 6250533 TI - Low-level chemiluminescence of hydroperoxide-supplemented cytochrome c. AB - Ferricytochrome c showed low-level chemiluminescence, with a light-emission measured of about 1x10(3)-3x10(3) counts/s, when supplemented with organic hydroperoxides. Tertiary hydroperoxides (cumene hydroperoxide and t-butyl hydroperoxide) showed a saturation behaviour at about 5mm-hydroperoxide, whereas primary hydroperoxides showed a quadratic dependence on the hydroperoxide concentration. Chemiluminescence depended linearly on cytochrome c concentration, and optimal light-emission was observed at [t-butyl hydroperoxide]/[ferricytochrome c] ratios of 160-500. Hydroperoxide-supplemented ferricytochrome c consumed O(2) at a rate of 1.0mumol/min per mumol of cytochrome c; the rate of O(2) uptake was linearly related to the concentration of cytochrome c. The Soret absorption band of ferricytochrome c decreased about 64% after incubation with t-butyl hydroperoxide, whereas the 530nm band was almost totally abolished. Light-emission was (a) inhibited competitively by cyanide. (b) inhibited by singlet-oxygen quenchers (e.g. beta-carotene), scavengers (e.g. dimethylfuran) and traps (e.g. histidine and tryptophan) and (c) increased by singlet-oxygen-chemiluminescence enhancer 1,4-diazabicyclo[2.2.2]-octane. Superoxide dismutase had no effect on the present system. The participation of free radicals is suggested by the effect of the radical trap 2,5-di-t butylquinol. Singlet-oxygen dimol emission seems to be mainly responsible for the observed light-emission; a mechanism that can account for the major part of the present experimental observations is proposed. PMID- 6250534 TI - An electrophoretic study of endogenous phosphorylation in vitro of the polypeptides of microsomal membrane fractions of mouse liver. AB - 1. The patterns of phosphopolypeptides produced by endogenous phosphorylation in vitro of rough- and smooth-membrane fractions of the microsomal fraction of mouse liver were studied by radioautographic analysis of sodium dodecyl sulphate/polyacrylamide-gel electrophoretograms. 2. A minimum of 17 polypeptides of both rough- and smooth-microsomal-membrane fractions were phosphorylated by using [gamma-(32)P]-ATP as the phosphate donor; only minor differences in phosphorylation pattern between the two membrane fractions were detected. 3. Phosphorylation in vitro by [gamma-(32)P]ATP was markedly stimulated by Mg(2+), but not by cyclic AMP, cyclic GMP or Ca(2+). The phosphorylation of certain polypeptides was preferentially stimulated by Mg(2+). Addition of cyclic AMP resulted in a decrease in the amount of (32)P detected in one polypeptide of mol.wt. approx. 56000, present in both the rough- and smooth-membrane fractions. 4. [gamma-(32)P]GTP was found to be a relatively poor donor of (32)P as compared with [gamma-(32)P]ATP. However, incubation of rough- and smooth-membrane fractions with this compound resulted in the phosphorylation of one polypeptide of mol.wt. approx. 96000 that was scarcely or not at all phosphorylated by [gamma (32)P]ATP. 5. Under the conditions of incubation used, appreciable incorporation of (32)P from [gamma-(32)P]ATP occurred into products migrating at the front of the electrophoretograms; these products were identified as being principally comprised of 1-phosphatidylinositol 4-phosphate. Incorporation of (32)P into this lipid was also markedly stimulated by Mg(2+). 6. The overall results show that a considerable number of polypeptides of the rough- and smooth-microsomal-membrane fractions of mouse liver may be phosphorylated in vitro and indicate that the enzymes responsible are principally non-cyclic AMP-dependent protein kinases. PMID- 6250535 TI - Selective release of plasma-membrane enzymes from rat hepatocytes by a phosphatidylinositol-specific phospholipase C. AB - When isolated hepatocytes are incubated with phosphatidylinositol-specific phospholipase C, three cell-surface enzymes show markedly different behaviour. Most of the alkaline phosphatase is released at very low values of phosphatidylinositol hydrolysis, whereas further phosphatidylinositol hydrolysis releases only a maximum of about one-third of the 5'-nucleotidase. Alkaline phosphodiesterase I is not released. If cells containing phosphatidyl[3H]inositol are similarly treated, then the released [3H]inositol is in the form of inositol phosphate: no evidence has been obtained for any covalent association between released [3H]inositol and alkaline phosphatase. PMID- 6250536 TI - Distribution of sequences common to the 25--28S-ribonucleic acid genes of Xenopus laevis and Neurospora crassa. AB - The extent of homology between the nucleotide sequence of L-rRNA (the major RNA component of the larger ribosomal subparticle) of a lower eukaryote (Neurospora crassa) and an amphibian (Xenopus laevis) was investigated by utilizing rDNA (DNA coding for rRNA) of X. laevis cloned in plasmids pMB9 and pML2, and rDNA of N. crassa cloned in bacteriophage lambda. Hybridization studies revealed that sequences common to both N. crassa and X. laevis L-rRNA comprise a total of approx. 1050 /+- 200 nucleotides. The thermal stability of the X. laevis rDNA.N. crassa L-rRNA hybrid was 5 degrees C lower than that of the X. laevis rDNA.X. laevis L-rRNA duplex, indicating the presence of fewer than 10% mismatches in homologous sequences. X. laevis rDNA was analysed by means of restriction endonucleases and hybridization with 125I-labelled N. crassa L-rRNA. Most (at least 95%) of the conserved sequences were present in a 3000-base-pair fragment produced by restriction with endonucleases HindIII and BamHI. This fragment, which includes the 3'-OH terminus of the L-rRNA-coding region, was used as an adaptor in the construction of a bacteriophage-lambda recombinant. One section of the recombinant phage terminating in a HindIII-specific site was obtained from bacteriophage lambda plac5 (after restriction with endonuclease HindIII). A second section terminating in a BamHi-specific site was obtained from bacteriophage lambda 540 (after restriction with endonuclease BamHI). These two parts were joined by means of the X. laevis rDNA fragment. Further analysis of cloned rDNA by means of restriction endonucleases confirmed that conserved sequences were widely distributed throughout the 3000-base-pair fragment produced by HindIII and BamHi endonucleases. A 3400-base-pair fragment of N. crassa rDNA cloned in a bacteriophage lambda [Cox & Peden (1979) Mol. Gen. Genet. 174, 17- 24] was restricted with endonucleases. The products were hybridized with 125I labelled X. laevis L-rRNA. Conserved sequences were shown to be distributed over a range of approx. 1600--2700 base-pairs. Hence, in neither X. laevis nor N. crassa L-rRNA can be conserved sequences from a single block; instead regions of high and low (or no) homology must be intermingled. Both N. crassa rDNA and X. laevis rDNA were found to hybridize with Drosophila melanogaster L-rDNA sequences. Those rDNA fragments with sequences common to X. laevis and N. crassa L-rRNA also hybridized with D. melanogaster L-rRNA probe. Thus the same set of conserved sequences may be present in all three species. PMID- 6250537 TI - Adenosine diphosphate ribose transferase from baby-hamster kidney cells (BHK 21/C13). Characterization of the reaction and product. AB - Some properties of ADP-ribose transferase, and its reaction product, from BHK 21/C13 cells are described. Enzyme activity was found almost exclusively in nuclei (90%), with the remaining 10% located in the cytosolic fraction. The nuclear enzyme is chromatin-bound and requires bivalent cations, preferably Mg2+, a pH of 8.0 and a temperature of 25 degrees C for optimal activity. Chromatin preparations incorporated radioactivity from [14C]NAD+ into acid-insoluble material for about 60 min. Kinetics for substrate NAD+ utilization were not of Michaelis--Menten type; biphasic kinetics were shown from a double-reciprocal plot (1/reaction velocity against 1/[NAD+]) and from a 'Hofstee' plot (reaction velocity/[NAD+] against reaction velocity). The transferase is unstable in the absence of Mg2+ ions. It is inhibited by thymidine, nicotinamide and nicotinamide analogues, but not by ATP, which stimulates it at concentrations of 5 mM and above. The enzyme requires thiol groups for activity; it is readily inhibited by N-ethylmaleimide at 0.5 mM. The product of the reaction is stable under acid conditions at temperatures up to 25 degrees C, but it is hydrolysed by HClO4 at 70 degrees C. It is resistant to NaOH, but is cleaved from its attachment to protein with alkali into trichloroacetic acid-insoluble and -soluble components. On the basis of Cs2SO4- density-gradient analysis under denaturing conditions (gradients included urea and guanidinium hydrochloride), and analysis of the reaction product directly on hydroxyapatite, we conclude that most of the radioactive ADP-ribose residues are firmly bound to protein, presumably in covalent linkage. Hydroxyapatite-chromatographic analysis of ADP-ribose residues released from protein by alkaline digestion showed a spectrum of molecular sizes including mono-, oligo- and poly-(ADP-ribose), when chromatin was incubated initially with [14C]NAD+ for 10 min and then for a further 30 min after addition of excess non-radioactive NAD+, only about 10% of the radioactive mono-(ADP ribose) could be 'chased' into longer-chain molecules. Hydroxyapatite analysis was also used to show that, whereas all ADP-ribose residues were released from protein with NaOH, only 50% of them were susceptible to hydroxylamine. These hydroxylamine-sensitive residues included all size classes, although mono-(ADP ribose) predominated. Finally, there was an approximately equal distribution of ADP-ribose incorporated into HCl-soluble proteins (including the histones) and HCl-insoluble proteins (including the non-histone proteins) when chromatin was incubated with NAD+ up to 0.5 mM, but at higher NAD+ concentrations more ADP ribose was incorporated into the HCl-soluble fraction (82% at 4.0 mM-NAD+). PMID- 6250538 TI - Consequences of hormone-induced desensitization of adenylate cyclase in intact cells. AB - A hypothesis on the role of the hormone-induced desensitization of adenylate cyclase is proposed. It is suggested that the desensitization process could provide the cell with a highly efficient cyclic AMP system for transmitting hormone stimulus without requiring a large energy consumption. Theoretical considerations show that in fact the desensitization phenomenon allows the cyclic AMP system to present a good compromise between the efficiency and economy requirements of the cells. PMID- 6250539 TI - Regulation of coenzyme A biosynthesis by glucagon and glucocorticoid in adult rat liver parenchymal cells. AB - We studied the effects of glucagon, dibutyryl cyclic AMP and dexamethasone on the rate of [(14)C]pantothenate conversion to CoA in adult rat liver parenchymal cells in primary culture. The presence of 30nm-glucagon increased the rate by about 1.5-fold relative to control cultures (range 1.4-2.3) and 2.4-fold relative to cultures containing 1-3m-i.u. of insulin/ml. The half-maximal effect was obtained at 3nm-glucagon. Dibutyryl cyclic AMP plus theophylline also enhanced the rate by about 1.5-fold. Dexamethasone acted synergistically with glucagon; glucagon at 0.3nm had no effect when added alone, but resulted in a 1.7-fold enhancement when added in the presence of dexamethasone (maximum effect at 50nm). The 1.4-fold enhancement caused by the addition of saturating glucagon concentrations was increased to a 3-fold overall enhancement by the addition of dexamethasone. However, dexamethasone added alone over the range 5nm to 5mum had no effect on the rate of [(14)C]pantothenate conversion to CoA. The stimulatory effect of dibutyryl cyclic AMP plus theophylline was also enhanced by the addition of dexamethasone. Changes in intracellular pantothenate concentration or radioactivity could not account for the stimulatory effects of glucagon, dibutyryl cyclic AMP or dexamethasone. Addition of 18mum-cycloheximide, an inhibitor of protein synthesis, decreased the rate of incorporation of [(14)C]pantothenate into CoA and the enhancement of this rate by glucagon and dibutyryl cyclic AMP plus theophylline in a reversible manner. These results demonstrate an influence of glucagon, dibutyryl cyclic AMP and glucocorticoids on the intracellular mechanism regulating total CoA concentrations in the liver. PMID- 6250541 TI - Modulation of neurotransmission by purine nucleotides and nucleosides. PMID- 6250540 TI - Dephosphorylation and activation of exogenous glycogen synthase by adipose-tissue phosphatase. AB - Exogenous purified rabbit skeletal-muscle glycogen synthase was used as a substrate for adipose-tissue phosphoprotein phosphatase from fed and starved rats in order to (1) compare the relationship between phosphate released from, and the kinetic changes imparted to, the substrate and (2) ascertain if decreases in adipose-tissue phosphatase activity account for the apparent decreased activation of endogenous glycogen synthase from starved as compared with fed rats. Muscle glycogen synthase was phosphorylated with [gamma-(32)P]ATP and cyclic AMP dependent protein kinase alone, or in combination with a cyclic AMP-independent protein kinase, to 1.7 or 3mol of phosphate per subunit. Adipose-tissue phosphatase activity determined with phosphorylated skeletal-muscle glycogen synthase as substrate was decreased by 35-60% as a consequence of starvation. This decrease in phosphatase activity had little effect on the capacity of adipose-tissue extracts to activate exogenous glycogen synthase (i.e. to increase the glucose 6-phosphate-independent enzyme activity), although there were marked differences in the activation profiles for the two exogenous substrates. Glycogen synthase phosphorylated to 1.7mol of phosphate per subunit was activated rapidly by adipose-tissue extracts from either fed or starved rats, and activation paralleled enzyme dephosphorylation. Glycogen synthase phosphorylated to 3mol of phosphate per subunit was activated more slowly and after a lag period, since release of the first mol of phosphate did not increase the glucose 6-phosphate independent activity of the enzyme. These patterns of enzyme activation were similar to those observed for the endogenous adipose-tissue glycogen synthase(s): the glucose 6-phosphate-independent activity of the endogenous enzyme from fed rats increased rapidly during incubation, whereas that of starved rats, like that of the more highly phosphorylated muscle enzyme, increased only very slowly after a lag period. The observations made here suggest that (1) changes in glucose 6 phosphate-independent glycogen synthase activity are at best only a qualitative measure of phosphoprotein phosphatase activity and (2) the decrease in glycogen synthase phosphatase activity during starvation is not sufficient to explain the differential glycogen synthase activation in adipose tissue from fed and starved rats. However, alterations in the phosphorylation state of glycogen synthase combined with decreased activity of phosphoprotein phosphatase, both as a consequence of starvation, could explain the apparent markedly decreased enzyme activation. PMID- 6250542 TI - The alpha-adrenergic mediated effect in rat liver. Correlation between [3H] dihydroergocryptine binding to plasma membranes and glycogen phosphorylase activation in isolated hepatocytes. PMID- 6250543 TI - Acetylcholine modulation of phosphorylase and contractility in rat hearts exposed to anoxia or isoproterenol. PMID- 6250544 TI - Effects of adenosine analogs and adenine nucleotides on adenosine 5'-diphosphate induced rat platelet aggregation. PMID- 6250545 TI - Evidence for the external location of alkaline phosphatase activity on the surface of Sarcoma 180 cells resistant to 6-thioguanine. PMID- 6250547 TI - Enzyme modifications that alter interactions of K+ and cardioactive steroids with (Na+ + K+)-dependent ATPase. PMID- 6250546 TI - Stimulatory effect of ionophores on adenosine 3',5'-monophosphate content in human mononuclear leukocytes. PMID- 6250548 TI - Biliary excretion of copper and zinc in the rat as influenced by diethylmaleate, selenite and diethyldithiocarbamate. PMID- 6250549 TI - Inhibition of buttermilk xanthine oxidase by folate analogues and derivatives. PMID- 6250550 TI - Influence of colchicine derivatives on lysosomal enzyme release from polymorphonuclear leukocytes and intracellular levels of cAMP after phagocytosis of monosodium urate crystals. PMID- 6250551 TI - Dexamethasone increases beta-adrenoceptor density in human astrocytoma cells. PMID- 6250552 TI - [Clinical and etiological data in 21 cases of Poland's syndrome]. AB - Clinical and etiological data of 21 cases of Poland's syndrome are reported. The anomaly was seen especially on the right side and was significantly more frequent in males than in females (4:1). The variable expressivity of the morphology of the ipsilateral hand is analyzed. Height of the hand was obtained in 18 cases. Simian crease and Sydney line are significantly more frequent in patients than in controls. These observations confirmed that unilateral isolate absence of the pectoralis major muscle is a mild expression of the syndrome. Most of the cases were sporadic. No difference was found in the number of spontaneous abortions between the mothers of patients and controls. In one family, it seems that a mother-to-child transmissin was present which could be explain by an autosomal dominant inheritance. PMID- 6250553 TI - Characterization of protein kinase activity associated with rat liver polysomal messenger ribonucleoprotein particles. AB - Poly(adenylic acid)-containing rat liver polysomal messenger ribonucleoprotein particles (pmRNP) were isolated and found to contain protein kinase activity. The association of the enzyme(s) with the particles was confirmed by experiments showing that the protein kinase activity comigrated with the pmRNP on metrizamide gradients and bound to oligo-(dT)-cellulose columns only under conditions where the pmRNP bound. The following properties were determined for the pmRNP associated kinase(s). Casein and phosvitin were preferred substrates over histone and protamine. The optimal MgCl2 and KCl concentrations were found to be 12.5 and 50 mM, respectively. MnCl2 and CaCl2 could not replace MgCl2 and were inhibitory at low concentrations. The optimum pH range was 7.7--9.0, and the enzyme activity was cAMP independent. A molecular weight of 55 000--60 000 was determined for the kinase(s) by sucrose gradient analysis. The enzyme(s) was capable of phosphorylating proteins endogenous to the pmRNP. Membrane-bound pmRNP contained much less kinase activity than free pmRNP while pmRNP from hepatoma 7777 contained an elevated level of the enzyme(s). The relationship between the protein kinase activity and one of the pmRNP proteins of molecular weight 66 000 is discussed. PMID- 6250554 TI - Structure of the cytochrome c oxidase complex: labeling by hydrophilic and hydrophobic protein modifying reagents. AB - Beef heart cytochrome c oxidase has been reacted with [35S]diazobenzenesulfonate ([35S]DABS), [35S]-N-(4-azido-2-nitrophenyl)-2-aminoethylsulfonate ([35S]NAP taurine), and two different radioactive arylazidophospholipids. The labeling of the seven different subunits of the enzyme with these protein modifying reagents has been examined. DABS, a water-soluble, lipid-insoluble reagent, reacted with subunits II, III, IV, V, and VII but labeled I or VI only poorly. The arylazidophospholipids, probes for the bilayer-intercalated portion of cytochrome c oxidase, labeled I, III, and VII heavily and II and IV lightly but did not react with V or VI. NAP-taurine labeled all of the subunits of cytochrome c oxidase. Evidence is presented that this latter reagent reacts with the enzyme from outside the bilayer, and the pattern of labeling with the different hydrophilic and hydrophobic labeling reagents is used to derive a model for the arrangement of subunits in cytochrome c oxidase. PMID- 6250555 TI - Conformationally restricted creatine analogues and substrate specificity of rabbit muscle creatine kinase. PMID- 6250556 TI - Location of the heme groups in cytochrome cd1 oxidase from Pseudomonas aeruginosa. AB - The disposition of the heme groups in cytochrome cd1 oxidase from Pseudomonas aeruginosa is studied by emission spectroscopy. This protein of molecular weight 120 000 is composed of two monomers each with a heme c and a heme d1. It has been shown by electron microscopy to be oblong in shape and by preliminary X-ray crystallography to have a twofold axis of rotation. Three electronic energy donors, a singlet tryptophan, a triplet tryptophan, and an attached 8 dimethylamino-1-naphthalenesulfonyl group, all exhibit normal decay lifetimes. It follows that there are parts of the protein at least 80 A from the nearest heme. The conclusion is that the hemes are all at one end of the molecule. PMID- 6250557 TI - lac Operator nucleosomes. 1. Repressor binds specifically to operator within the nucleosome core. AB - We have shown that the lac repressor can recognize and bind specifically to the lac operator contained in short restriction fragments which have been complexed with the four core histones to form artificial nucleosomes and core particles. These lac reconstitutes have been well characterized, and it is apparent that the operator DNA itself is associated fully and normally with the octameric histone cores. The binding of repressor to these reconstitutes is operator dependent since nucleosomes lacking the operator sequence fail completely to bind repressor under our conditions. Moreover, binding is abolished by IPTG (isopropyl thiogalactoside), further demonstrating operator specificity. Nevertheless, sedimentation studies show that repressor binding does not involve displacement of the histone octamer. Thus, the lac repressor and the histone octamer bind simultaneously to the same DNA. lac reconstitutes, in which the DNA has been cross-linked to the histones with formaldehyde, also support simultaneous specific binding by lac repressor. Since all particles among the reconstitutes, cross-linked or not, bind repressor quantitatively, we infer that the repressor binding surface of the operator DNA always faces generally outward rather than inward toward the histone core. It is likely to be this feature of lac operator particle structure, dictated in an unknown manner by DNA sequence, that allows the simultaneous binding of histones and repressor to the same DNA region. PMID- 6250558 TI - lac Operator nucleosomes. 2. lac Nucleosomes can change conformation to strengthen binding by lac repressor. AB - We have shown previously that lac repressor binds specifically and quantitatively to lac operator restriction fragments which have been complexed with histones to form artificial nucleosomes (203 base pair restriction fragment) or core particles (144 base pair restriction fragment. We describe here a quantitative method for determining the equilibrium binding affinities of repressor for these lac reconstitutes. Quantitative analysis shows that the operator-histone reconstitutes may be grouped into two affinity classes: those with an affinity for repressor close to that of naked DNA and those with an affinity 2 or more orders of magnitude less than that of naked DNA. All particles in the lac nucleosome preparations bind repressor with high affinity, but the lac core particle preparations contain particles of both high and low affinities for repressor. Formaldehyde cross-linking causes all high-affinity species to suffer a 100-fold decrease in binding affinity. In contrast, there is no effect of cross linking on species of low affinity. Therefore, the ability of a particle to be bound tightly by repressor depends on a property of the particle which is eliminated by cross-linking. Control experiments have shown that chemical damage to the operator does not accompany cross-linking. Therefore, the property sensitive to cross-linking must be the ability of the particle to change conformation. We infer that the particles of low native affinity, like cross linked particles, are of low affinity because of an inability to facilitate repressor binding by means of this conformational change. Dimethyl suberimidate cross-linking experiments show that histone-histone cross-linking is sufficient to preclude high-affinity binding. Thus, the necessary conformational change involves a nucleosome histone core event. We find that the ability of a particle to undergo a repressor-induced facilitating conformational change appears to depend on the position of the operator along the DNA binding path of the nucleosome core. We present a general model which proposes that nucleosomes are divided into domains which function differentially to initiate conformational changes in response to physiological stimuli. PMID- 6250559 TI - Biochemistry of terminal deoxynucleotidyltransferase: identification, characterization, requirements, and active-site involvement in the catalysis of associated pyrophosphate exchange and pyrophosphorolytic activity. AB - Terminal deoxynucleotidyltransferase (TdT) has been found to catalyze both pyrophosphate exchange and pyrophosphorolysis reactions. Both reactions are strongly inhibited by antiserum to TdT. The reactions require the presence of a divalent cation, a single- or double-stranded oligomeric or polymeric DNA or RNA, and deoxyribonucleoside triphosphates (for PPi exchange only). Of the three divalent cations tested, Mg2+ and Co2+ are equally effective, while Mn2+ neither is used for catalysis nor inhibits the Mg2+-catalyzed reactions. Ribonucleoside triphosphates have been found to support the PPi exchange reaction to a minor extent and have no inhibitory effect on the catalysis mediated by dNTPs. Inhibition studies, using SH group inhibitors, Zn chelator, and a substrate binding site specific reagent, revealed that PPi exchange and pyrophosphorolysis reactions may be distinguished by differences in their sensitivity to inhibition by various reagents. While the PPi exchange reaction is strongly inhibited by sulfhydryl reagents, o-phenanthroline, and pyridoxal phosphate, the pyrophosphorolysis reaction is insensitive to these reagents. In addition, the pyrophosphorolysis reaction is also found not to require a free 3'-OH terminus of a primer. This difference in the susceptibility of the two reactions indicates that discrete active-site structures exist in TdT which catalyze PPi exchange and pyrophosphorolysis reactions. PMID- 6250560 TI - Photoreactive derivatives of corticotropin. 1. Preparation and chracterization of 2,4-dinitro-5-azidophenylsulfenyl derivative of corticotropin. AB - A photoaffinity probe for corticotropin (ACTH) receptors was prepared by selective modification of the single tryptophan residue in ACTH. A new photoreactive agent, 2,4-dinitro-5-azidophenylsulfenyl chloride, was synthesized and used for introducing the photoreactive group into ACTH. 2,4-Dinitro-5 azidophenylsulfenyl-Trp9-ACTH (DNAPS-ACTH) was also prepared by thiolysis of 2,4 dinitrophenyl-sulfenyl-Trp9-ACTH to form 2-thiol-Trp9-ACTH and reaction of this with 2,4-dinitro-5-azidofluorobenzene. DNAPS-ACTH was characterized by ultraviolet spectra, peptide mapping, and amino acid analysis. Covalent attachment of DNAPS-ACTH to a pituitary protein fraction FI by photolysis was demonstrated by ultraviolet absorption changes as well as by the use of tritiated DNAPS-ACTH. PMID- 6250561 TI - Photoreactive derivatives of corticotropin. 2. Preparation and characterization of 2-nitro-4(5)-azidophenylsulfenyl derivatives of corticotropin. AB - Two new photoreactive arylsulfenyl chlorides, 2-nitro-4-azidophenylsulfenyl chloride (2,4-NAPS-Cl) and 2-nitro-5-azidophenylsulfenyl chloride (2,5-NAPS-Cl), have been synthesized and used for the selective modification of corticotropin (ACTH). Both reagents reacted rapidly with N-acetyltryptophanamide and ACTH under acidic conditions. The NAPS derivatives of ACTH were purified by partition chromatography and characterized by absorption spectra, amino acid analysis, and peptide mapping. The spectral changes caused by photolysis as well as the kinetics of photolysis are described. Tritiated 2,5-NAPS-ACTH was attached covalently to a pituitary protein fraction FI by photolysis. The photolabeling of FI was blocked in the presence of excess ACTH. PMID- 6250562 TI - Characterization of the slowly dissociable human growth hormone binding component of isolated rat hepatocytes. AB - Human growth hormone (hGH) bound to specific sites on rat hepatocytes. The time course of hGH dissociation was comprised of more than one component. Dissociation was resolved into rapid (t1/2 = 10.5 min) and slow (t 1/2 = 6.4 h) fractions. The amount of slowly dissociable hormone increased for the first 75 min during which time cells and [125I]hGH associated. Subsequently, the amount of slowly dissociable hGH was constant. The time courses of hGH receptor binding and subsequent retention of slowly dissociable label were similar. The capacity of hepatocytes to accumulate slowly dissociable label was saturated by hGH over the same concentration range as the high-affinity binding site (KD approximately 2 nM). This suggested that a receptor-mediated process was responsible for the accumulation of slowly dissociable hGH. Rapidly dissociable label was intact [125I]hGH and fragments resulting from growth hormone degradation. Slowly dissociable hGH recovered from hepatocytes by acid extraction was intact and immunocompetent. There was a large increase in the extent of [125I]hGH degradation between 23 and 37 degrees C. Over this temperature range, the proportion of hGH not in rapid equilibrium with the medium decreased. High concentrations of hGH decreased the amount of slowly dissociable [125I]hGH retained by hepatocytes by competing for high-affinity sites. The interaction of [125I]hGH with low-affinity degradative systems was favored by the presence of hGH. The temperature and concentration dependencies of hGH retention and degradation distinguished these proceses. PMID- 6250563 TI - Interconversion between different states of affinity of the human growth hormone receptor on rat hepatocytes: effects of fractional site occupancy on receptor availability. AB - Isolated rat hepatocytes accumulate a slowly dissociable human growth hormone (hGH) binding fraction with incubation time. Slowly dissociable [125I]hGH is receptor bound, intact and immunocompetent. Fifty-six percent of the bound hormone was slowly dissociable within 3 min of the initiation of hGH-hepatocyte incubation. Subsequently, the proportion of slowly dissociable [125I]hGH increased at the expense of the rapidly dissociable fraction. This suggested that binding induced interconversion between different states of affinity of the hGH receptor. Preincubation with hGH diminished the capacity of hepatocytes to subsequently bind [125I]hGH. Receptor occupancy resulting from accumulation of slowly dissociable hGH accounted for 37 and 62% of the decreased binding after preincubation with 0.79 and 7.9 nM hGH, respectively. Fractional receptor occupancy, among but distinguishable from other processes, may account for the inverse relationship between site number and applied hormone concentration. Addition of hGH to the medium of [125I]-hGH-hepatocyte incubates increased the extent of loss of label from hepatocytes. The progressive retention of intact [125I]-hGH by hepatocytes with site occupancy and invariant receptor affinity subsequent to fractional saturation was inconsistent with negative cooperativity. A mechanism in which hGH diminished reassociation of [125I]hGH with available sites during dissociation was consistent with the available binding data. The interrelationship between peptide hormone in rapid and slow equilibrium with the medium is of fundamental importance in modulating receptor binding and availability. PMID- 6250564 TI - Characterization of octapeptin-membrane interactions using spin-labeled octapeptin. AB - Octapeptin is a membrane-active peptide antibiotic that contains a C10 fatty acid covalently attached to the peptide through an amide bond. Interactions of octapeptin with bacterial membranes and phospholipids were characterized by using spin-labeling techniques and octapeptin derivatives containing fatty acids of varying chain length. Acyl modification of octapeptin demonstrated that the fatty acid of the antibiotic contributed to the antimicrobial activity of octapeptin and its affinity for membranes. The influence of octapeptin and C2 acyloctapeptin on the rates of ascorbate reduction of several membrane-bound doxyl stearates was also examined. These studies demonstrated that octapeptin increaed the rate of diffusion of ascorbate into the lipid bilayer and suggested that the acyl chain contributed to this activity. In addition, an acyl spin-labeled analogue of octapeptin was prepared and shown to retain biological activity. Spectral analysis showed that octapeptin does not aggregate in solution over a wide concentration range. However, the isotropic splitting constant indicated that the acyl chain of octapeptin is not completely exposed to water. It is proposed that the acyl chain of octapeptin in solution interacts with hydrophobic amino acids in the peptide, which partially shields the acyl chain from water. Spectral features of the spin-labeled antibiotic bound to phospholipid dispersions were consistent with directional binding of octapeptin to lipid bilayers with insertion of the fatty acid into the hydrocarbon domain. PMID- 6250565 TI - Oxidation of cytochromes c and c2 by bacterial photosynthetic reaction centers in phospholipid vesicles. 1. Studies with neutral membranes. AB - The oxidation of cytochrome c2 by photosynthetic reaction center isolated from Rhodopseudomonas sphaeroides and incorporated into unilamellar phosphatidylcholine vesicles was found to be kinetically similar to that observed earlier for reaction centers in low detergent solution [Overfield, R.E., Wraight, C.A., & DeVault, D. (1979) FEBS Lett. 105, 137-142]. At low ionic strength the kinetics were biphasic. The fast phase indicated the formation of a cytochrome reaction center complex with an apparent binding constant, KB, of about 10(5) M 1. However, KB decreased dramatically with increasing salt concentration, and no fast oxidation was detectable in 0.1 M NaCl. The slow cytochrome oxidation was first order in both cytochrome and reaction centers and, thus, second order overall. Deviations from theoretical second-order behavior were observed when the rate of the first-order back reaction of the primary photoproducts was significant compared to the cytochrome oxidation. This can cause serious overestimation of the second-order rate constant. The slow oxidation of cytochrome c2 by reaction centers in phosphatidylcholine vesicles exhibited a 40% lower encounter frequency than with the solubilized reaction center. This was attributed to the much lower diffusion coefficient of the reaction center in the vesicle membrane than in solution. No effects of diminished dimensionality were detected with neutral vesicles. An activation energy of 8.0 +/- 0.4 kcal x mol-1 was determined for the slow phase of cytochrome c2 oxidation by reaction centers in solution and in vesicles of several different phosphatidylcholines, including dimyristoylphosphatidylcholine above and below its phase transition temperature. Thus, the physical state of the lipid did not appear to affect any rate-limiting steps leading to cytochrome oxidation. The ionic strength dependence of the slow kinetics of oxidation of cytochromes c and c2 confirmed the electrostatic nature of the cytochrome-reaction center interaction, and the pH dependence indicated the titration of a group or groups, important to this interaction, at pH 9.5. PMID- 6250566 TI - Oxidation of cytochromes c and c2 by bacterial photosynthetic reaction centers in phospholipid vesicles. 2. Studies with negative membranes. PMID- 6250567 TI - Chromatium vinosum cytochrome c-552. Reduction by photoreduced flavins and intramolecular electron transfer. AB - Cytochrome c-552 from Chromatium vinosum is an unusual heme protein in that it contains two hemes and one flavin per molecule. To investigate whether intramolecular electron transfer occurs in this protein, we have studied its reduction by external photoreduced flavin by using pulsed-laser excitation. This approach allows us to measure reduction kinetics on the mirosecond time scale. Both fully reduced lumiflavin and lumiflavin semiquinone radical reduce cytochrome c-552 with second-order rate constants of approximately 1.4 x 10(6) M 1s-1 and 1.9 x 10(8) M-1 s-1, respectively. Kinetic and spectral data and the results of similar studies with riboflavin indicate that both the flavin and heme moieties of cytochrome c-552 are reduced simultaneously on a millisecond time scale, with the transient formation of a protein-bound flavin anion radical. This is suggested to be due to rapid intramolecular electron transfer. Further, steric restrictions play an important role in the reduction reaction. Studies were conducted on the redox processes following photolysis of CO-ferrocytochrome c-552 in which the flavin was partly oxidized to resolve the kinetics of electron transfer between the heme and flavin of cytochrome c-552. Based on these results, we conclude that intramolecular electron transfer from ferrous heme to oxidized flavin occurs with a first-order rate constant of greater than 1.4 x 10(6) s-1. PMID- 6250568 TI - Comparison of glycopeptides from control and virus-transformed baby hamster kidney fibroblasts. AB - Glucosamine-labeled glycopeptides from control and virus-transformed BHK fibroblasts were characterized by size, lectin affinity, charge, and composition. As already demonstrated, on the basis of elution position on a column of Sephadex G-50, transformed cells contained a greater proportion of large glycopeptides than did control cells. Transformed cells also contained a larger proportion of glycopeptides which do not bind to Con A-Sepharose. By sequential chromatography on Sephadex G-50, Con A-Sepharose, and DEAE-Sephadex, approximately 40 individual peaks were partially or completely resolved. If sialic acid was removed from the glycopeptides prior to analysis by ion-exchange chromatography, 95% of the glycopeptides from control cells and 85% of the glycopeptides from transformed cells were no longer bound by DEAE-Sephadex. It was concluded that the DEAE Sephadex elution properties of the glycopeptides are determined almost entirely by the sialic acid content of the molecules. A comparison of the profiles of control and transformed cell glycopeptides simultaneously eluting from columns of DEAE-Sephadex revealed that the differences between the two cells were largely quantitative; however, the possibility of the existence of qualitative differences as well cannot be excluded. In particular, there was one component present on the surface of transformed cells that was virtually absent in control cells. It was degraded by nitrous acid hydrolysis and heparinase and appeared to be heparan sulfate like material. After fractionation, each isolated glycopeptide population was analyzed for carbohydrate and, in some cases, amino acid content. The apparently larger glycopeptides, group A, the dominant population in transformed cells, were found to contain 3 to 4 mannose residues/glycopeptide when the sugars were normalized to sialic acid content. On the basis of the same criteria, group B glycopeptides contained 4-6 mannose residues/glycopeptide. The carbohydrate and amino acid compositions of the glycopeptides from transformed cells were, with a few exceptions, similar to those from control cells. Some isolated glycopeptides appeared to contain both O-glycosidic anad N-glycosidic linkages on the same oligopeptide. PMID- 6250569 TI - Phosphatidylcholine exchange protein catalyzes the net transfer of phosphatidylcholine to model membranes. AB - 2-Stearoyl spin-labeled phosphatidylcholine (PC*) has been introduced into the phosphatidylcholine exchange protein from bovine liver and its electron spin resonance (ESR) spectrum determined. The spin-labeled group in the PC*- exchange protein complex was strongly immobilized. Addition of sodium deoxycholate micelles released PC* from its binding site, producing a mobile signal. This was also observed when micelles of lysophosphatidylcholine and vesicles of phosphatidic acid were added, indicating that the exchange protein can insert its endogenous PC* into interfaces devoid of phosphatidylcholine. ESR spectroscopy was used to measure transfer of PC* from spin-labeled "donor" vesicles to unlabeled "acceptor" vesicles as described by Machida & Ohnishi [Machida, K., & Ohnishi, S. (1978) Biochim. Biophys. Acta 507, 156-164]. The donor vesicles consisted of PC* and phosphatidic acid (75:25 mol%) and the acceptor vesicles of phosphatidylethanolamine and phosphatidic acid (81:19 mol%). Addition of exchange protein catalyzed a net transfer of PC* from donor to acceptor vesicles. This transfer proceeded until the acceptor vesicles contained approximately 2 mol% of PC*. A spontaneous transfer of PC* was not observed. As for the mode of action, it appears that the exchange protein, after insertion of its endogenous PC* into the acceptor, leaves the interface without a bound phospholipid molecule yet continues to shuttle PC* from donor to acceptor. PMID- 6250570 TI - Binding of Escherichia coli ribonucleic acid polymerase holoenzyme to a bacteriophage T7 promoter-containing fragment: selectivity exists over a wide range of solution conditions. AB - The selectivity of binding of Escherichia coli RNA polymerase holoenzyme to a promoter-containing fragment of T7 DNA has been investigated over a range of solution conditions by using a double-label nitrocellulose filter binding assay. A 32P-labeled HaeIII restriction fragment of T7 D111 DNA containing the A1 and D promoters for the E. coli enzyme and a 3H-labeled nonpromoter HaeIII fragment of comparable size were incubated with sigma-saturated holoenzyme and filtered through a nitrocellulose membrane filter. We find that the extent of binding of polymerase to the promoter-containing fragment decreases dramatically with increasing salt concentrations and with increasing pH and increases moderately with increasing temperature in the range 0-37 degrees C. By contrast, the nonspecific interaction of polymerase with the nonpromoter fragment is known to be relatively insensitive to pH and temperature, though a strong function of salt concentration [deHaseth, O. L., Lohman, T. M., Burgess, R. R., & Record, M. T., Jr. (1978) Biochemistry 17, 1612-1622]. Selectivity of binding of RNA polymerase in our assay is demonstrated by a greater fractional retention of the promoter containing fragment than of the nonpromoter fragment on the filter. We observe selective binding over the temperature range from 0 to 37 degrees C near neutral pH and over a wide range of Na+ concentrations, in the presence or absence of Mg2+. Because of the different dependences of promoter and nonpromoter binding on pH and temperature, the extent of selectivity increases with increasing temperature and decreases with increasing pH. Quantitative treatment of these binding data [Strauss, H. S., Burgess, R. R., & Record, M. t., Jr. (1980) Biochemistry (second paper of four in this issue)] confirms these conclusions and shows that selectivity is a function of ion concentration as well. PMID- 6250571 TI - Use of difference boundary sedimentation velocity to investigate nonspecific protein-nucleic acid interactions. AB - The difference boundary sedimentation velocity technique of Schachman and co workers is demonstrated to be applicalbe to the measurement of binding constants (Kobsd) in the range 10(2)-10(5) M(-1) for the nonspecific interactions of proteins with DNA. The difference technique can reproducibly detect a 2% change in the sedimentation coefficient of the DNA upon binding ligands, corresponding to average extents of association as low as 10 molecules of protein (in the cases of Escherichia coli lac repressor and E. coli RNA polymerase) per molecule of bacteriophage T7 DNA. At these low binding densities, it is plausible to assume that the primary effect of ligand binding is on the buoyant mass of the complex and not on the frictional coefficient of the flexible DNA coil. Binding constants calculated by using this assumption agree well with literature values for the nonspecific interactions of RNase and lac repressor proteins with double-stranded DNA. Advantages of the method are that it is relatively rapid, requires the optical detection of the DNA only, and can be performed on small amounts of sample. The method appears useful for surveying (to an accuracy of +/-50% in Kobsd or +/-10% in log Kobsd) the effects of solution variables on Kobsd of protein-DNA interactions. Applications of the method to the nonspecific interactions of RNA polymerase core and holoenzymes with T7 DNA are discussed. PMID- 6250572 TI - Isolation and properties of a mitochondrial protein that converts succinate dehydrogenase into succinate-ubiquinone oxidoreductase. PMID- 6250573 TI - Electron paramagnetic resonance detectable states of cytochrome P-450cam. AB - Cytochrome P-450cam is a low-spin Fe3+hemoprotein (g = 2.45, 2.26, and 1.91) which is made 60% high spin (g = 7.85, 3.97, and 1.78) at 12 K by the addition of 1 mol of substrate per mol of enzyme. Low-temperature EPR spectra show that the low-spin fraction of substrate-bound P-450cam contains two magnetic species. The majority species has an unusual EPR spectrum (g = 2.42, 2.24, and 1.97) which connot be simulated by using the range of crystal field parameters known for other heme proteins. The minority species has the same g values as substrate-free enzyme. Both low-spin species show Curie law temperature dependence below 50 K and have similar saturation behavior. Above 50 K the g = 2.42, 2.24, and 1.97 species rapidly loses signal intensity. The distribution of low-spin species is pH dependent (apparent pKa = 6.2) with the g = 2.42, 2.24, and 1.97 magnetic species favored at high pH. The substrate binding stoichiometry and the equilibria observed in the low-spin fraction suggest that there are not multiple protein forms of cytochrome P-450cam. Putidaredoxin and other effector molecules which specifically catalyze hydroxylation convert either the high-spin or the g = 2.42, 2.24, and 1.97 low-spin species to another new magnetic species (g = 2.47, 2.26, and 1.91). This species is only seen in the presence of substrate, and its stability reflects the catalytic potency of the effector molecule. The EPR and UV visible spectra of cytochrome P-420 depend upon the manner in which the P-420 is generated. Incubation with acetone or reaction with N-ethylmaleimide or diethyl pyrocarbonate generates P-420 with different spectral characteristics. Through identification of active-site amino acids by chemical modification and comparison with porphyrin model complexes, the range of ligands likely to participate in each of the EPR detectable species is assigned. Mechanisms of interconversion of these species and their bearing on catalysis are discussed. PMID- 6250574 TI - Investigation of the essential boundary layer phospholipids of cytochrome c oxidase using Triton X-100 delipidation. PMID- 6250575 TI - Proteolytic cleavage of methionyl transfer ribonucleic acid synthetase from Bacillus stearothermophilus: effects on activity and structure. AB - Methionyl-tRNA synthetase from Bacillus stearothermophilus, a dimer of molecular weight 2 X 85K, is converted by limited subtilisin digestion into a fully active monomeric fragment of molecular weight 64K. The reversible methionine activation reaction of these enzymes was followed through the variation of the intensity of their trypotophan fluorescence. Equilibrium and stopped-flow experiments show that the rate and mechanism for adenylate formation supported by the monomeric derivative are undistinguishable from those of each adenylating site of the native dimeric enzyme. In contrast, the rate of tRNA aminoacylation is improved upon limited proteolysis of the native enzyme. This behavior can be related to the anticooperativity of the binding of tRNA molecules to native dimeric enzyme. Accordingly, at 25 degrees C, the dimer might behave as a half-of-the-sites enzyme with only one active tRNA site at a time, compared to two after limited proteolysis with consequent irreversible disociation into two 64K fragments. Another modified form of the enzyme is obtained through limited tryptic digestion. This derivative is completely devoid of activity although its molecular weight under nondenaturating conditions remains undistinguishable from that of the 64K fragment generated by subtilisin. Denaturation reveals that this tryptic derivative is composed of two subfragments with molecular weights of 33K and 29K, respectively. The same fragments may also be directly obtained through limited tryptic digestion of the subtilsic fragment. Interestingly, although trypsin treatment has abolished the activity of the enzyme, fluorescence studies demonstrate that the ATP and methionine binding sites have remained intact. It is shown that the effect of the internal cut made by trypsin into the active 64K fragment has been to considerably depress the "coupling" between the methionine and nucleotide binding sites. Finally, the rate of inactivation of the enzyme by trypsin is observed to be substantially decreased by in situ synthetized methionyl adenylate but not by tRNA. These properties and others are discussed in relation to the problem of its significance of repeating sequences and structural "domains" within the class of aminoacyl-tRNA synthetases. PMID- 6250576 TI - Cloning and determination of a putative promoter region of a mouse ribosomal deoxyribonucleic acid fragment. AB - An endonuclease EcoRI digest of mouse DNA was subjected to molecular cloning, after partial purification with respect to the ribosomal RNA sequence, using lambda gtWES x lambda B with an in vitro packaging technique. Twelve positive clones were obtained from approximately 2 X 10(4) plaques. One of the clones transferred to the plasmid pBR322 (PMrEL-1) was about 14.9 kb long, hybridizing only with 18S rRNA but not with 28S rRNA. Hybridization of restriction fragments and electron microscopic studies of the R-loop confirmed that this fragment carried about half of the 18S rRNA sequences at one end, suggesting that it contained the initiation site for the 45S preribosomal RNA (pre-rRNA). S1 nuclease protection mapping with hybrids between restriction fragments of the cloned DNA and the 45S pre-rRNA indicated that at least major transcription of the 45S RNA started at a site approximately 4.0 kb upstream from the 5' end of the 18S rRNA. This was confirmed by electron microscopic observations of these hybrids. PMID- 6250577 TI - Calcium-induced exposure of a hydrophobic surface on calmodulin. AB - Interactions between calmodulin (CaM) and several hydrophobic fluorescent probes were characterized in order to determine if CaM expresses hydrophobic binding sites in the presence of Ca2+. Several classes of fluorescent probes capable of sensing exposure of hydrophobic binding sites on proteins were found to bind to CaM, and these interactions were greatly enhanced by Ca2+. In the presence of Ca2+, the fluorescence intensity of 9-anthroylcholine (9AC) was increased 24-fold by CaM, with a shift in the fluorescence emission maximum from 514 to 486 nm. The fluorescence intensity of 8-anilino-1-naphthalenesulfonate (Ans) was enhanced 27 fold with an emission maximum shift from 540 to 488 nm in the presence of CaM and Ca2+. Similar results were obtained with the uncharged fluorescent ligand, N phyenyl-1-naphthylamine. With all three fluorescent dyes, the fluorescence changes caused by CaM in the absence of Ca2+ were minor compared to those observed with CaM and Ca2+. Direct binding studies using equilibrium dialysis demonstrated that CaM can bind four to six molecules of 9AC or two to three molecules of Ans in a calcium-dependent manner. The effects of various amphiphilic compounds on the Ca2+-dependent complex formation between CaM and the Ca2+-sensitive phosphodiesterase or troponin I were investigated. Trifluoperazine (TFP) and 9AC inhibited CaM stimulation of the Ca2+-sensitive phosphodiesterase. The Ca2+-dependent binding of the phosphodiesterase to CaM-Sepharose was also inhibited by TFP, 9AC, and Ans. Furthermore, binding of CaM to troponin I Sepharose was inhibited by these ligands. Consistent with these data was the observation that troponin I antagonized binding of 9AC to CaM. These data indicate that binding of Ca2+ to CaM results in exposure of a domain with considerable hydrophobic character, and binding of hydrophobic ligands to this domain antagonizes CaM-protein interactions. It is proposed that this hydrophobic domain may serve as the interface for the Ca2+-dependent binding of CaM to the phosphodiesterase or troponin I. PMID- 6250578 TI - Synthesis of [3 beta-3H]-3-epivitamin D3 and its metabolism in the rat. AB - 3-Epivitamin D3, the 3 alpha epimer of vitamin D3, was synthesized, and its biological activity in the rat was evaluated. It was found to be approximately 4 times less active on a weight basis than vitamin D3 with respect to intestinal calcium transport, bone calcium mobilization, and calcification score as determined by the line-test assay. Tritiated 3-epivitamin D3 was prepared, and its metabolism in the rat was compared with that of vitamin D3 to investigate the reasons for this diminished activity. 3-Epivitamin D3 was converted to two polar metabolites, for which the chromatographic properties and the origin of biosynthesis (in the liver and kidney, respectively) correspond to 25-hydroxy-3 epivitamin D3 and 1 alpha,25-dihydroxy-3-epivitamin D3. The fact that the concentration of 1 alpha,25-dihydroxy-3-epivitamin D3 in the intestine is half that of 1 alpha,25-dihydroxyvitamin D3 may be one explanation for the reduced biological activity of this epimer. PMID- 6250579 TI - Mechanism of benzo[a]pyrene diol epoxide induced deoxyribonucleic acid strand scission. AB - Approximately 1% of (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy 7,8,9,10-tetrahydrobenzo[a]pyrene (BaP-diol epoxide) DNA alkylation sites rearrange with strand scission at neutral pH. Phosphotriester hydrolysis and depurination/depyrimidination strand scission were critically examined as possible mechanisms for this phenomenon. The catalysis of nicking by alkali and the inhibition of nicking by counterions were consistent with either mechanism. The kinetics of nicking, however, were characteristic of a multistep reaction such as depurination/depyrimidination strand scission and the detection of apurinic sites in BaP-diol epoxide alkylated DNA strongly supported this mechanism. The number of such sites, especially at lower reaction levels, was probably sufficient to account for strand scission. No direct evidence was obtained for nicking occurring through phosphotriester hydrolysis. Studies with model substrates, including dibutyl phosphate, DNA homopolymers, and TMV RNA, indicated that if BaP-diol epoxide forms phosphotriesters in DNA or RNA, they do not hydrolyze with strand scission. Besides apurinic/apyrimidinic sites, a second alkali-sensitive rearrangement product was present in BaP-diol epoxide modified DNA. These latter sites accumulated with time and after 24 h accounted for as much as 4% of the initial alkylation events. Although relatively stable at neutrality, they spontaneously nicked the DNA backbone at high pH. It is possible that these sites represent a rearrangement of the major N2 guanine adduct. PMID- 6250580 TI - Glycolate formation catalyzed by spinach leaf transketolase utilizing the superoxide radical. AB - A homogeneous preparation of transketolase was obtained from spinach leaf; the specific enzyme activity was 9.5 mumolo of glyceraldehyde-3-P formed (mg of protein)-1 min-1, when xylulose-5-P and ribose-5-P were used as the donor and acceptor, respectively, of the ketol residue. Transketolase catalyzed the formation of glycolate from fructose-6-P coupled with the O2- -generating system of xanthine-xanthine oxidase. The addition of superoxide dismutase (145 units) or 1,2-dihydroxybenzene-3,5-disulfonic acid (Tiron) (5 mM), both O2- scavengers, to the reaction system inhibited glycolate formation 72 and 58%, respectively. The reacton was not inhibited by catalase. Mannitol, an .OH scavenger, and beta carotene and 1,4-diazobicyclo[2.2.2]octane, 1O2 scavengers, showed little or no inhibitory effects. The rate of glycolate formation catalyzed by the transketolase system was measured in a coupled reaction with a continuous supply of KO2 dissolved in dimethyl sulfoxide, used as an O2- -generating system. The optimum pH of the reaction was above pH 8.5. The second-order rate constant for the reaction between transketolase and O2-, determined by the competition for O2- between nitroblue tetrazolium (NBT) and transketolase, was 1.0 X 10(6) M-1 s-1. Transketolase showed an inhibitory effect on the O2- -dependent reduction of NBT only if the reaction mixture was previously incubated with ketol donors such as fructose-6-P, xylulose-5-P, or glycolaldehyde. The results suggest the possibility that transketolase catalyzes O2- -dependent glycolate formation under increased steady-state levels of O2- in the chloroplast stroma. PMID- 6250581 TI - Inactivation of Bacillus cereus beta-lactamase I by 6 beta-bromopenicillanic acid: kinetics. AB - The kinetics of the inactivation of Bacillus cereus beta-lactamase I by 6 beta bromopenicillanic acid are described. Loss of beta-lactamase activity is accompanied by a decrease in protein fluorescence, by the appearance of a protein bound chromophore at 326 nm, and by loss of tritium from 6 alpha-[3H]-6 beta bromopenicillanic acid. It is shown that all of the above changes probably have the same rate-determining step. The inactivation reaction is competitively inhibited by cephalosporin C, a competitive inhibitor of this enzyme, and by covalently bound clavulanic acid, suggesting that 6 beta-bromopenicillanic acid reacts directly with the beta-lactamase active site. It is proposed that this inhibitor reacts initially as a normal substrate and that the rate-determining step of the inactivation is acylation of the enzyme. A rapid irreversible inactivation reaction rather than normal hydrolysis of the acyl-enzyme then follows acylation; 6 beta-bromopenicillanic acid is thus a suicide substrate. PMID- 6250582 TI - Studies on human lactoferrin by electron paramagnetic resonance, fluorescence, and resonance Raman spectroscopy. AB - Investigations of metal-substituted human lactoferrins by fluorescence, resonance Raman, and electron paramagnetic resonance (EPR) spectroscopy confirm the close similarity between lactoferrin and serum transferrin. As in the case of Fe(III)- and Cu(II)-transferrin, a significant quenching of apolactoferrin's intrinsic fluorescence is caused by the interaction of Fe(III), Cu(II), Cr(III), Mn(III), and Co(III) with specific metal binding sites. Laser excitation of these same metal-lactoferrins produces resonance Raman spectral features at ca. 1605, 1505, 1275, and 1175 cm-1. These bands are characteristic of tyrosinate coordination to the metal ions as has been observed previously for serum transferins and permit the principal absorption band (lambda max between 400 and 465 nm) in each of the metal-lactoferrins to be assigned to charge transfer between the metal ion and tyrosinate ligands. Furthermore, as in serum transferrin the two metal binding sites in lactoferrin can be distinguished by EPR spectroscopy, particularly with the Cr(III)-substituted protein. Only one of the two sites in lactoferrin allows displacement of Cr(III) by Fe(III). Lactoferrin is known to differ from serum transferrin in its enhanced affinity for iron. This is supported by kinetic studies which show that the rate of uptake of Fe(III) from Fe(III)--citrate is 10 times faster for apolactoferrin than for apotransferrin. Furthermore, the more pronounced conformational change which occurs upon metal binding to lactoferrin is corroborated by the production of additional EPR-detectable Cu(II) binding sites in Mn(III)-lactoferrin. The lower pH required for iron removal from lactoferrin causes some permanent change in the protein as judged by altered rates of Fe(III) uptake and altered EPR spectra in the presence of Cu(II). Thus, the common method of producing apolactoferrin by extensive dialysis against citric acid (pH 2) appears to have an adverse effect on the protein. PMID- 6250583 TI - Alkyl glycoside detergents: a simpler synthesis and their effects on kinetic and physical properties of cytochrome c oxidase. AB - Octyl glucoside is an effective, nonionic, solubilizing agent for membrane proteins with the advantage of ease of removal by dialysis. In order to study the detergent-sensitive activity of cytochrome c oxidase, we chose this detergent because of its simple structure and the possibility of synthesizing analogues to test the structural dependence of the detergent specificity. A procedure was therefore developed that facilitates large-scale preparation of octyl glucoside and related alkyl glycosides, improving on previous methods by eliminating crystallization steps and employing a one-step purification of the final product on Dowex 1. This new purification procedure is particularly important for achieving the level of purity required to obtain the disaccharide, longer alkyl chain detergents in soluble form. Of the alkyl glycosides prepared (octyl beta-D glucopyranoside, octyl beta-D-lactopyranoside, dodecyl beta-D-lactopyranoside, dodecyl beta-D-cellobiopyranoside, and dodecyl beta-D-maltopyranoside), lauryl (dodecyl) maltoside was found to be the most successful as an activator of purified beef and Neurospora cytochrome oxidase, giving two- to tenfold higher activities than octyl glucoside and other commercially available detergents, Tween-20 and Triton X-100. Kinetic studies using two different steady-state assay systems indicate that the activity changes are not the result of altered binding of the substrate but rather reflect a detergent effect on the state of association of the enzyme (as a monomer, dimer, or polymer) as well as on its intrinsic activity. By gel filtration procedures, lauryl maltoside and octyl glucoside were found to exist as monodisperse populations of micelles of 50 000 and 8000 daltons, respectively. The small uniform micelles and chemically well defined structures of lauryl maltoside and octyl glucoside make them superior to other nonionic detergents for the study of membrane proteins in general and cytochrome oxidase in particular, since its activity in lauryl maltoside most closely approaches that of the physiological state. PMID- 6250584 TI - Deoxyribonuclease I sensitivity of the nontranscribed sequences flanking the 5' and 3' ends of the ovomucoid gene and the ovalbumin and its related X and Y genes in hen oviduct nuclei. PMID- 6250585 TI - Temperature dependence of beta receptor, adenosine receptor, and sodium fluoride stimulated adenylate cyclase from turkey erythrocytes. AB - The individual temperature dependencies of the process which control the activity of turkey erythrocyte adenylate cyclase have been determined. The temperature dependence of the fraction of activable cyclase units experiences a thermal transition at 24 degrees C for all three modes of enzyme activation: l epinephrine, adenosine, and NaF. This thermal transition probably reflects the phase transition in the inner monolayer of the membrane which influences the behavior of the GTP regulatory unit which is involved in all three modes of enzyme activation. The "rate constant" of enzyme activation by adenosine reflects two thermal transitions, at 24 and at 35 degrees C; the apparent rate constant of cyclase activation by NaF activation experiences a transition only at 24 degrees C whereas the rate constant of the beta-receptor-bound agonist decreases monotonously with no "breaks" on the Arrhenium plot. Following the temperature dependence of the fluorescence intensity of dansylphosphatidylethanolamine embedded in both sides of the membrane and exclusively in the outer monolayer, one can assign the thermal transition of 24 degrees C to the inner monolayer and the other two transitions to the outer monolayer (10 and 35 degrees C). We interpret these results as follows. (a) The monomolecular rate constant characterizing the activation of cyclase by the precoupled adenosine receptor experiences both the transition at 24 and 35 degrees C, indicating that the latter may span the bilayer. (b) The bata receptor activates the cyclase units only in fluid areas since it can diffuse exclusively in the fluid areas of the membrane and is unable to interact with cyclase units in "frozen" areas. the linear dependence of the logarithm of the rate constant on 1/T for the bata receptor reflects the change of membrane fluidity as a function of temperature. PMID- 6250587 TI - Specific solvent effects on the thermal denaturation of ribonuclease. Effect of dimethyl sulfoxide and p-dioxane on thermo dynamics of denaturation. AB - Differential scanning calorimetry has been used to study the thermal denaturation of ribonuclease in aqueous dimethyl sulfoxide and acqueous p-dioxane. A two-state reversible denaturation occurs in acqueous dimethyl sulfoxide. The denaturation is irreversible in aqueous p-dioxane. The transition temperatuire decreases in both organic solvents, with p-dioxane producing a considerably greater effect. The enthalpy of the denaturation initially increases with increasing dimethyl sulfoxide concentration and then decreases at high concentrations. Similar behavior is observed in the entropy in the dimethyl sulfoxide solutions. The enthalpy of the denaturation decreases markedly with low p-dioxane concentrations. Changes in pH due to presence of organic solvent cannot account for the changes in enthalpy of denaturation. Addition of organic solvent tends to increase the pH of the ribonuclease solution. Higher pH in aqueous solutions gives a high transition temperature, whereas addition of organic solvent results in the opposite bahavior. The relative changes in the two solvents systems suggest that specific solvent effects occur and that destablization of the native state relative to the denatured state is greater with p-dioxane than with dimethyl sulfoxide. PMID- 6250586 TI - Parallel modulation of catecholamine activation of adenylate cyclase and formation of the high-affinity agonist.receptor complex in turkey erythrocyte membranes by temperature and cis-vaccenic acid. PMID- 6250588 TI - Ubiquinol-cytochrome c reductase (EC 1.10.2.2). Isolation in triton X-100 by hydroxyapatite and gel chromatography. Structural and functional properties. AB - 1. A mehod for the isolation of a monodisperse ubiquinol-cytochrome c reductase (complex III) from beef heart mitochondria has been developed. The procedure consists of an enzyme solubilization in Triton X-100 followed by hydroxyapatite and gel chromatography. 2. The minimum unit of the isolated complex is composed of 9 polypeptide subunits with Mr of 49000, 47000, 30000, 25000, 12000, 11000 and 6000. It contains 8 mumol of cytochrome b, 4 mumol of cytochrome c1, 7-8 mumol of nonhemne iron, corresponding to 3.5-4 mumol of the Rieske iron-sulfur protein, less than 1.0 mumol of ubiquinone and about 60 mumol of phospholipids, per g of protein. The specific detergent binding amounts to 0.2g of Triton X-100 per g protein. 3. Cytochrome b exhibits an alpha-absorbance maximum at 562 nm. In redox titrations it reveals two half-reduction potentials, i.e. -10 and + 100 mV, at pH 7.0. The absorbance maximum of cytochrome c1 lies at 553 nm and its half reduction potential amounts to +250 mV. 4. The reductase reveals electron transferring activity with ubiquinol-1, -2, -3, and -9 as donor and cytochrome c as acceptor. The activity with ubiquinol-9 was analyzed according to the surface dilution scheme developed for the action of phospholipases. The molecular activity amounts to 75 mol of cytochrome c reduced per s at 20%C. 5. A dissociation constant K's of 5.5 mM has been determined for the Tritonsolubilized enzyme: ubiquinol-containing micelle association. In this case the total concentration of ubiquinol plus Triton X-100 has been substituted for the concentration of binding areas on the ubiquinol-containing micelles. This substitution makes the reasonable assumption that the sum of ubiquinol concentration plus Triton X-100 is proportional to the number of available binding areas. 6. A K'm value of 0.025 was found for ubiquinol-9. This is an analog to the Michaelis constant and is expressed as mol fraction of ubiquinol in the ubiquinol-Triton micelle. PMID- 6250589 TI - Use of specific trifluoroacetylation of lysine residues in cytochrome c to study the reaction with cytochrome b5, cytochrome c1, and cytochrome oxidase. AB - The preparation, purification, and characterization of four new derivatives of cytochrome c trifluoroacetylated at lysines 72, 79, 87, and 88 are reported. The redox reaction rates of these derivatives with cytochrome b5, cytochrome c1 and cytochrome oxidase indicated that the interaction domain on cytochrome c for all three proteins involves the lysines immediately surrounding the heme crevice. Modification of lysines 72, 79, 87 had a large effect on the rate of all three reactions, while modification of lysine 88 had a very small effect. Even though lysines 87 and 88 are adjacent to one another, lysine 87 is at the top left of the heme crevice oriented towards the front of cytochrome c, while lysine 88 is oriented more towards the back. Since the interaction sites for cytochrome c1 and cytochrome oxidase are essentially identical, cytochrome c probably undergoes some type of rotational diffusion during electron transport. PMID- 6250590 TI - The orientation of the magnetic axes of the membrane-bound iron-sulfur clusters of spinach chloroplasts. AB - Spinach chloroplast membranes were oriented onto mylar sheets by partial dehydration, and the orientation of the magnetic axes of membrane-bound paramagnetic clusters determined by electron paramagnetic resonance (EPR) spectroscopy. Our results indicate that the reduced Rieske iron-sulfur cluster signal is of orthorhombic symmetry oriented with th gy = 1.90 axis orthogonal to the membrane plane and with the gz = 2.03 axis in the membrane plane; the gx-axis is undetectable, presumably due to its broadness. If the Rieske center is a two iron iron-sulfur cluster, we conclude that the iron-iron axis lies in the plane of the membrane. Illumination reduces the two bound chloroplast iron-sulfur proteins known as Clusters A and B. Center A is oriented such that gx = 1.86 and gy = 1.94 lie at an angle of about 40, and gz = 2.05 is at approximately 25, to the membrane plane. There are two possible orientations of Cluster B depending on the set of g-values assigned to this cluster. For one set of g-values, gz = 2.04 and gx = 1.89 are oriented in the plane of the membrane while gy = 1.92 is orthogonal to the plane. Alternatively, gz = 2.07 and gy = 1.94 are oriented approximately 50 and 40 to the membrane plane respectively, and gx = 1.80 is in the plane of the membrane. An additional light-induced signal at g = 2.15 oriented orthogonal to the plane is currently unexplained, as are other membrane perpendicular signals seen at g = 2.3 and g = 1.73 in dark-adapted samples. PMID- 6250591 TI - Structural changes in (Na+ + K+)-ATPase accompanying detergent inactivation. AB - Structural changes in the purified (Na+ + K+)-ATPase accompanying detergent inactivation were investigated by monitoring changes in light scattering, intrinsic protein fluorescence, and tryptophan to beta-parinaric acid fluorescence resonance energy transfer. Two phases of inactivation were observed using the non-ionic detergents, digitonin, Lubrol WX and Triton X-100. The rapid phase involves detergent monomer insertion but little change in protein structure or little displacement of closely associated lipids as judged by intrinsic protein fluorescence and fluorescence resonance energy transfer. Lubrol WX and Triton X-100 also caused membrane fragmentation during the rapid phase. The slower phase of inactivation results in a completely inactive enzyme in a particle of 400 000 daltons with 20 mol/mol of associated phospholipid. Fluorescence changes during the course of the slow phase indicate some dissociation of protein-associated lipids and an accompanying protein conformational change. It is concluded that non-parallel inhibition of (Na+ + K+) ATPase and p-nitrophenylphosphate activity by digitonin (which occurs during the rapid phase of inactivation) is unlikey to require a change in the oligomeric state of the enzyme. It is also concluded that at least 20 mol/mol of tightly associated lipid are necessary for either (Na+ + K+)-ATPase or p nitrophenylphosphatase activity and that the rate-limiting step in the slow inactivation phase involves dissociation of an essential lipid. PMID- 6250592 TI - The role of extracellular calcium ions in HVJ (Sendai virus)-induced cell fusion. AB - The biochemical and biophysical roles of extracellular calcium ions in HVJ (Sendai virus)-induced cell fusion were studied. (1) Various kinds of cell, such as Ehrlich ascites tumor cells, mouse melanoma cells (B16-CW1 cells) and human epidermoid carcinoma cells (KB cells), could fuse in Ca2+-free medium containing a cheletor, glycoletherdiaminetetraacetic acid, in the same way as in Ca2+ containing medium. (2) The ATP content in Ehrlich ascites tumor cells decreased rapidly when the cells were treated with the virus in Ca2+-free medium but not in Ca2+-containing medium. (3) Intracellular adenine nucleotides leaked out into the reaction medium when the cells were treated with the virus in Ca2+-free medium but not in Ca2+-containing medium. (4) On addition of the virus, O2 consumption of Ehrlich ascites tumor cells decreased in Ca2+-free medium, but not in Ca2+ containing medium. (5) HVJ (Sendai virus) did not affect production of lactate by Ehrlich ascites tumor cells in both Ca2+-free medium and Ca2+-containing medium. These observations suggest that the role of extracellular Ca2+ in virus-induced cell fusion is to maintain the ATP and other intracellular metabolite contents at normal levels instead of triggering the fusion reaction itself. PMID- 6250593 TI - Trypsin-induced masking of tetrodotoxin receptor of the sodium channels in mollusc neurons. AB - At the early stage of trypsin treatment of mollusc neurons tetrodotoxin cannot block the Na+ current. In the course of further exposure of neurones to trypsin, tetrodotoxin-sensitivity is restored completely, so its temporal loss results from shielding rather than destruction of the tetrodotoxin-binding site. Pronase and papain do not affect the tetrodotoxin action on the Na+ current. PMID- 6250594 TI - An investigation of membrane fluidity changes during sporulation and germination of Bacillus megaterium K.M. measured by electron spin and nuclear magnetic resonance spectroscopy. AB - Changes in membrane and macromolecular fluidity which may accompany the differentiation processes of sporulation and germination in Bacillus megaterium K.M. are examined by electron spin and nuclear magnetic resonance spectroscopy. No change in membrane lipid fluidity is observed in isolated forespores up to stage VI. Between stage VI and release of mature spores, the ESR spectrum of doxylstearic acid spin labels becomes polycrystalline. This change in spectral fluidity is completely reversed during germination and is paralleled by the rapid release of Ca2+ from the spore. NMR studies also show that the mature spore has reduced macromolecular mobility and an increased nonexchangeable water pool compared with vegetative cells. PMID- 6250595 TI - Surface membrane redistribution and stabilization of concanavalin A-specific receptors following Yaba tumor poxvirus infection. AB - Monkey kidney cells productively infected with Yaba tumor poxvirus clearly exhibit plasma membrane alterations when treated with both fluorescein-labeled and unlabeled concanavalin A. The convanavalin A-mediated cytoagglutination reaction for Yaba-infected Jinet and CV-1 cells increased linearly from 12 to 16 h post-infection, reaching a maximum by 24-28 h. Treatment of either Yaba infected CVC-1 or Jinet cells with methyl-D-glucopyranoside before or after addition of concanavalin A completely blocked or reversed the cytoaglutination response. Trypsin treatment of uninfected CV-1 or Jinet cells enhanced concanavalin A-mediated cytoagglutination properties. Conversely, trypsin treatment of Yaba-infected Jinet cells resulted in a reduced cytoagglutination response. Increasing temperature and lectin concentration enhance concanavalin A mediated cytoagglutination for uninfected, trypsin-treated and Yaba-infected CV-1 cells. Cytosine arabinoside has little or no effect on the Yaba-induced cell cytoagglutination reaction while cycloheximide blocks the cytoagglutinatin response if added prior to 12 h post-infection. Fluorescein-labeled concanavalin A binding studies have revealed that at 4 degrees C, Yaba-infected CV-1 cells display a predominantly 'patchy' pattern of topological fluorescence, while trypsin-treated and uninfected CV-1 cells at 4 degrees C display a uniform pattern of fluorescence binding. Patchy fluorescence, indicative of concanavalin A-suspeptible, receptor-site clustering on the surface membrane, was reduced 50% if Yaba-infected CV-1 cells were treated with glutaraldehyde (2.5%) before addition of fluorescein-labeled concanavalin A at 4 degrees C. Similar pre fixatin of trypsin-treated CV-1 cells resulted in uniform, fluorescent labelling patterns at all assay temperatures. PMID- 6250596 TI - Characterization of a temperature-sensitive membrane alteration in chick embryo fibroblasts infected with a temperature-sensitive mutant of Rous sarcoma virus. AB - The intramembrane particles of freeze-fractured chick embryo fibroblasts transformed with a temperature-sensitive mutant of Rous sarcoma virus (TS68) are distributed differently at the permissive and non-permissive temperatures if, and only if, the cells are treated with glycerol before fixation. Few aggregates of intramembrane particles are present in glycerol-treated cells grown at the permissive temperature for transformation (36 degrees C), while numerous large aggregates of particles are present at the non-permissive temperature (41 degrees C). Changes in the distribution of particles after cells are shifted from 36 to 41 degrees C are observed after 20 min, while a temperature shift from 41 to 26 degrees C causes changes in glycerol-induced redistributions after 1 h. The changes observed in temperature shifts from 36 to 41 degrees C and from 41 to 36 degrees D do not require protein synthesis or RNA synthesis. PMID- 6250597 TI - Interaction of divalent cations and proteins with phospholipid vesicles. AB - The broadening of spin-label absorption lines resulting from spin-exchange reactions that occur during collision with paramagnetic Ni2+ is diminished when Ni2+ binds to phospholipid vesicles. Subsequent addition of non-paramagnetic ions that compete for binding sites releases Ni2+ into solution and restores the line broadening. The concentrations of various ions required to achieve this effect was used to order the ions with respect to their binding to vesicles containing phosphatidylethanolamine and phosphatidylglycerol. The relative strengths of binding for those ions studied were: Ca2+ > Mg2+ > Zn2+ > Sr2+ > Ba2+. The spin broadening assay was also used to study the effects of two proteins on the availability of Ni2+-binding sites on the vesicles. Ribonuclease, which is thought to associate electrostatically as an extrinsic protein on the surface of vesicles, completely blocked the Ni2+-binding sites at comparatively low protein concentrations. Quantitative considerations of these data suggest the possibility that Ni2+ may bind preferenetially to phosphatidylglycerol, and that these binding sites are aggregated in the ribonuclease-containing vesicles. In contract to ribonuclease, cytochrome c does not block Ni2+-bindings sites on the phospholipid vesicles, but rather contains sites of its own that bind Ni2+, both when the protein is in solution and when it is associated with the vesicles. These results are consistent with other studies which suggest that cytochrome c becomes partially embedded in membrane bilayers and associates with phospholipid molecules through hydrophobic interactions. PMID- 6250598 TI - Membrane-bound protein kinase activity in acetylcholine receptor-enriched membranes. AB - Membrane protein phosphorylation may be a general regulatory mechanism mediating the response of cells to exogenous metabolic and physical signals. We have determined that the membrane-bound acetylcholine receptor is the major substrate phosphorylated in situ by a nearby membrane protein kinase. Moreover, these same membranes also contain phosphoprotein phosphatase activity which dephosphorylates the membrane-bound receptor. These findings suggest that reversible phosphorylation of the actylcholine receptor may be critical for receptor function at the synapse. Therefore, it is necessary to define the properties of the enzymes which mediate this phosphorylation-dephosphorylation mechanism. In this report we describe the properties of the first component of this system, the membrane-bound protein kinase in receptor-enriched membranes from the electric organ of Torpedo californica. Only ATP is effective as a phosphate donor for this cyclic AMP-independent membrane kinase; GTP does not support phosphorylation of the receptor. Both casein and histone can also be phosphorylated by the membrane protein kinase, but casein is a better substrate. Although phosphorylation of the receptor appears to be regulated by cholinergic ligands and K+, casein phosphorylation is not specifically affected by these agents. Moreover, while phosphorylation of the acetylcholine receptor is maximal in receptor=enriched membranes, casein phosphorylation is similar in all membrane fractions prepared from the electric organ. Taken together, these findings suggest that the membrane protein kinase activity in receptor-enriched membranes is similar to most other membrane kinases. Therefore, the unique characteristics of membrane-bound acetylcholine receptor phosphorylation appear to be determined by the receptor and its availability as a substrate for the membrane kinase. PMID- 6250599 TI - A study of the rate of chelation of magnesium by CDTA and EDTA in the ATP (NA+ + K+)-ATPase system. PMID- 6250600 TI - Apparent pyridoxine transport mutants of Escherichia coli with pyridoxal kinase deficiency. AB - By nitrosoguanidine treatment of a vitamin B-6 auxotroph (KG980) of Escherichia coli, mutants were isolated that require for growth markedly higher concentrations of pyridoxine than the parent strain. One of the mutants, strain HN1, exhibited a severely reduced ability to take up extracellular pyridoxine. Besides, cell-free extracts of HN1 showed an extremely low activity to phosphorylate pyridoxine compared to that of KG980. These findings together with other results suggest that phosphorylation of pyridoxine is essential for the concentration uptake of the vitamin. PMID- 6250601 TI - The diffusion-solubility of oxygen in lipid bilayers. AB - The product, Do alpha, of the oxygen diffusion coefficient, Do, and the oxygen solubility, alpha, is determined in phosphatidylcholine bilayers at temperatures above the lipid phase transitions from ESR spin-exchange measurements. The resulting values of Do alpha are in good agreement with those obtained from fluorescence-quenching experiments. The use of fatty acid spin labels makes it possible to measure Do alpha as a function of the coordinate perpendicular to the bilayer surface. The results indicate that do alpha is a strong function of this coordinate; it is greatest in the bilayer center and least near the bilayer head groups. PMID- 6250602 TI - Separation of basolateral plasma membranes from smooth endoplasmic reticulum of the rat enterocyte by zonal electrophoresis on density gradients. AB - Basolateral plasma membranes of rat small intestinal epithelium were purified by density gradient centrifugation followed by zonal electrophoresis on density gradients. Crude basolateral membranes were obtained by centrifugation in which the marker enzyme, (Na+ + K+)-ATPase, was enriched 10-fold with respect to the initial homogenate. The major contaminant was a membrane fraction derived from smooth endoplasmic reticulum, rich in NADPH-cytochrome c reductase activity. The crude basolateral membrane preparation could be resolved into the two major components by subjecting it to zonal electrophoresis on density gradients. The result was that (Na+ + K+)-ATPase was purified 22-fold with respect to the initial homogenate. Purification with respect to mitochondria and brush border membranes was 35- and 42-fold, respectively. Resolution of (Na+ + K+)-ATPase from NADPH-cytochrome c reductase by electrophoresis was best with membrane material from adult rats between 180 and 250 g. No resolution between the two marker enzymes occurred with material from young rats of 125 to 140 g. These results demonstrate that zonal electrophoresis on density gradients, a simple and inexpensive technique, has a similar potential to free-flow electrophoresis. PMID- 6250603 TI - Imipramine and lipid phase transition in inner mitochondrial membrane. AB - As ascertained by freeze-fracture electron microscopy, imipramine prevents lateral phase separation from taking place in inner mitochondrial membranes at sub-zero temperatures. Electron spin resonance (ESR) measurements performed on mitochondrial membranes labeled with the N-oxyl-4',4'-dimethyloxazolidine derivative of 16-ketostearic acid, show that the spin probe motion is markedly inhibited below 0 degree C and that 5 mM imipramine attenuates the temperature effect. These results are explained by supposing that imipramine is able to decrease the transition temperature of the inner mitochondrial membrane lipids as it does for simple lipid systems. PMID- 6250604 TI - Effects of cations of the plasma membrane of Blastocladiella emersonii zoospores An ESR study. AB - The physical properties of the plasma membrane of the aquatic phycomycete Blastocladiella emersonii were investigated, in particular the effects of cations on membrane structure. Intact zoospores and lipid extracts were labelled with the spin-labels 5-nitroxystearate (5-NS), 12-nitroxystearate (12-NS), and 2,2,6,6 tetramethylpiperidine-1-oxyl (Tempo). Electron spin resonance spectroscopy indicated a total of three breaks in plots of the hyperfine splitting parameter, 2T parallel, order parameter, S, and the partition coefficient, f, vs. temperature. The first and third break points (TL and TH) were found to be independent of the external K+, Ca2+, or Mg2+ concentrations. They were similar to the break points found in aqueous dispersions of lipid extracts and correlate well with the temperature limits for zoospore liability. In contrast, the middle break point (TM) was markedly influenced by the external Ca2+ concentration. Ca2+ increased TM from 12 degrees C (no Ca2+ added) to 22 degrees C (10 mM Ca2+), i.e., growth temperature. K+ reversed this Ca2+ effect, downshifting TM from 22 degrees C to 10 degrees C. A comparison of the physico-chemical effects of these ions on the membrane, as revealed by the cation-induced shift in TM, is closely correlated with the temperature dependence and physiological effects of cations on zoospore differentiation. This suggest that cations may modify the physical state of the plasma membrane and be involved in regulating the initial changes during zoospore encystment. PMID- 6250605 TI - Electron spin resonance study of the isolated lipid components from Blastocladiella emersonii zoospores. AB - The physico-chemical properties of lipid components isolated from zoospores of the aquatic phycomycete, Blastocladiella emersonii, were investigated with electron spin resonance (ESR) spectroscopy using the spin label, 5 nitroxystearate. Lipid dispersions were made from zoospore phospholipids and glycolipids, both singly and in combination with each other and with isolated neutral lipid components. Plots of the hyperfine splitting parameter (2T parallel) vs. temperature indicate that it is the zoospore glycolipids rather than the phospholipids which are responsible for the phase transformations previously observed in aqueous dispersions of the total lipids extracted from zoospores and in zoospores in vivo. The discontinuities observed in the glycolipid dispersions seem to represent the onset and completion of a gel-to liquid-crystalline phase transition. Over the temperature range tested, Ca2+ increased the rigidity of the glycolipid dispersions, the major component of which is probably a diglucosyldiglyceride, but had no effect on the phospholipid dispersions. The increase in 2T parallel was not affected by inclusion of neutral lipids into the glycolipid dispersion but was eliminated at high (5 : 1, w/w) phospholipid-to-glycolipid ratios. The Ca2+ effect was relatively independent of both the absolute rigidity of the dispersion and its phase (gel or liquid crystalline), suggesting an interaction with the glycolipid head group rather than the hydrocarbon core. The Ca2+-induced increase in 2T was neither prevented nor reversed by the presence of K+. The presence of two spin label populations co existing in a dynamic equilibrium was found in glycolipid/neutral lipid dispersions. Plots of the percentage ([HA/(HA + HB)] X 100 of the spin label population, as measured by the peak height of the low-field peaks, corresponding to the more immobilized component (HA) vs. temperature indicated two break points. The temperatures at which these break points occurred are similar to those obtained for the glycolipid dispersions, and match the break points (TL and TH) found in ESR experiments using zoospores in vivo. The importance of the glycolipids in the development of this organism is discussed. PMID- 6250606 TI - Interaction of pyrethroids with the Na+ channel in mammalian neuronal cells in culture. AB - The interaction of a series of pyrethroids with the Na+ channel of mouse neuroblastoma cells has been followed using both an electrophysiological and a 22Na+ influx approach. By themselves, pyrethroids do not stimulate 22Na+ entry through the Na+ channel (or the stimulation they give is too small to be analyzed). However, they stimulate 22Na+ entry when used in conjunction with other toxins specific for the gating system of the channel. These include batrachotoxin, veratridine, dihydrograyanotoxin II or polypeptide toxins like sea anemone and scorpion toxins. This stimulatory effect is fully inhibited by tetrodotoxin with a dissociation constant of 1.6 nM for the tetrodotoxin-receptor complex. Half-maximum saturation of the pyrethroid receptor on the Na+ channel is observed in the micromolar range for the most active pyrethroids, Decis and RU 15525. The synergism observed between the effect of pyrethroids on 22Na+ influx on the one hand, and the effects of sea anemone toxin II, Androctonus scorpion toxin II, batrachotoxin, veratridine and dihydrograyanotoxin II on the other, indicates that the binding component for pyrethroids on the Na+ channel is distinct from the other toxin receptors. It is also distinct from the tetrodotoxin receptor. Some of the pyrethroids used in this study bind to the Na+ channel but are unable to stimulate 22Na+ entry. These inactive compounds behave as are unable to stimulate 22Na+ entry. These inactive compounds behave as antagonists of the active pyrethroids. An electrophysiological approach has shown that pyrethroids by themselves are active on the Na+ channel of mammalian neurones, and essentially confirm the conclusions made from 22Na+ flux measurements. Pyrethroids are also active on C9 cells in which Na+ channels are 'silent', that is, not activatable by electrical stimulation. Pyrethroids chemically activate the silent Na+ channel in a manner similar to that with veratridine, batrachotoxin, or polypeptide toxins, which are known to slow down the inactivation process of a functional Na+ channel. PMID- 6250607 TI - Stimulus-response coupling in the human neutrophil. Transmembrane potential and the role of extracellular Na+. AB - Receptor-ligand interactions at the surface of the human neutrophil induce lysosomal enzyme release and the generation of O2.-, responses which are anteceded by changes in the membrane potential (delta psi) as measured by [3H] triphenylmethylphosphonium ion distribution. Surface stimuli (immune complexes, concanavalin A) initiated a rapid (less than 10 s) hyperpolarization response by both normal and cytochalasin B-treated cells. Replacement of extracellular Na+ with either K+ or choline depressed O2.- generation and lysosomal enzyme release in neutrophils exposed to concanavalin A or immune complexes. Replacement of Na+ with K+ led to a substantial fall in resting membrane potential, whereas replacement of Na+ with choline did not. Thus, depression of O2.- generation and lysosomal enzyme release in Na+-free medium were specifically due to a lack of extracellular Na+ and not to depolarization of the membrane. Although it has been shown that extracellular Na+, and possibly an influx of Na+, is required for optimal neutrophil function, neither depolarization nor Na+ influx per se was sufficient to activate fully these cells, since the Na+ ionophore, monensin, was not an effective stimulus for beta-glucuronidase release or O2.- generation. The hyperpolarization response to neutrophils exposed to immune complexes and to concanavalin A was greatly diminished in both high [K+] and [choline] buffers. Thus, extracellular Na+ was required for an optimal membrane potential response to receptor-ligand interaction. Since O2.- generation and lysosomal enzyme release in response to the Ca2+ ionophore, A23187, were also reduced in the absence of extracellular Na+, it was concluded that extracellular Na+ was also required after induction of Ca2+ fluxes. Ouabain (1 mM) had no effect on O2.- generation, lysosomal enzyme release or the hyperpolarization response to immune complexes, indicating that the hyperpolarization observed on stimulation cannot be due to the action of the electrogenic pump, (Na+ + K+)-ATPase. The experiments indicate that extracellular Na+ is required (1) in the delta psi response triggered by receptor-ligand interaction, and (2) at a step(s) subsequent to Ca2+ fluxes and common to O2.- generation and lysosomal enzyme release. PMID- 6250608 TI - S-substituted derivatives of 6-mercaptopurine ribosides interact both with the transport and metabolic phosphorylation of uridine by virus-transformed hamster fibroblasts. AB - The uptake of uridine by mammalian cells consists of transport of uridine across the plasma membrane followed by its metabolic conversion, mainly by phosphorylation. S-substituted aromatic derivatives of 6-mercaptopurine ribosides are potent inhibitors of the nucleoside uptake systems in human erythrocytes and in mammalian cells in culture and have been studied extensively. We present here a theoretical analysis which enables one to decide whether transport of metabolites, their metabolic trapping within the cell, or both, are susceptible to inhibition. This analysis was applied in the study of the effect of some inhibitors on uridine and cytosine-beta-D-arabinoside uptake by transformed Nil-8 cells. It was found that in Nil-SV cells, both transport and metabolic conversion are susceptible to inhibition by nitrobenzylmercaptoinosine and by dansylaminoethylmercaptoguanosine. Nitrobenzylmercaptoinosine displays inhibition constants of 20 and 7 nM for transport and phosphorylation, respectively, while for dansylaminoethylmercaptoguanosine the inhibition constants are 1.8 and 0.6 microM, respectively, for the same processes. Cytosine-beta-D-arabinoside is a synthetic nucleoside which is not metabolizable in Nil cells. Its uptake properties are determined by the transport mechanism alone. The transport of this nucleoside into Nil-SV cells in inhibited by nitrobenzylmercaptoinosine and the inhibition constant found is approx. 5 times greater than that for uridine. PMID- 6250609 TI - The induction of (Na+ + K+)-ATPase in the salt gland of the duck. PMID- 6250610 TI - Analysis of phosphoryl transfer mechanism and catalytic centre geometries of transport ATPase by means of spin-labelled ATP. AB - Spin-labelled ATP [3'-O-(1-oxyl-2,2,5,5-tetramethyl-3-carbonyl pyrrolidine) adenosine 5'-triphosphate], abbreviated SL-ATP, is used to study firstly the occurrence of an associative phosphorane mechanism for the phosphoryl transfer from ATP to the transport-ATPase protein, and secondly the presence of two geometrically unequal catalytic centres in the two catalytic peptide chains deduced to explain the existence of two KD'(ATP) values under equilibrium conditions and two Km(ATP) values under turnover conditions. 1. In the presence of Na+, K+ and Mg2+, SL-ATP is not hydrolysed by transport-ATPase from three different sources. In the presence of Na+ and Mg2+, SL-ATP reacts initially like ATP with the enzyme, as indicated by the production of a similar ouabain-binding protein conformation. With both nucleotides, this initial reaction includes the formation of the covalent enzyme-nucleotide complex through nucleophilic attack of the aspartate carboxyanion of the catalytic centre on the terminal phosphorus atom of the triphosphate chain. This produces the ouabain-binding conformation of the enzyme. Unlike ATP, the covalent enzyme-SL-ATP complex resists further transformation. 2. In the presence of Na+, K+ and Mg2+, the influence of SL-ATP on ATP hydrolysis by transport-ATPase depends on the ATP concentration chosen. At low ATP concentration, when the enzyme works as Na+-ATPase, SL-ATP does not affect the rate of ATP cleavage. At high ATP concentration, however, when the enzyme works as (Na+ + K+)-ATPase, SL-ATP reduces the rate of ATP hydrolysis to the level of Na+-ATPase activity, apparently due to the formation of the covalent enzyme-SL-ATP complex. 3. SL-ATP in the covalent enzyme-SL-ATP complex shows an ESR spectrum which is indistinguishable regarding the overall shape, the rotational correlation time, tau, and the hyperfine coupling constant, aN, from the ESR spectrum of free SL-ATP. Consequently, the dimensions of the catalytic centre cleft of transport-ATPase provide the labelled group of SL-ATP, opposite to its 3'-O-esterification site at the ribose moiety, in a wide-cleft groove, enough free space for an essentially unhindered rotational mobility within an aqueous environment like that of the bulk medium. Judged from literature data, similarly wide grooves exist in the catalytic centre clefts of mitochondrial and myosin ATPases. 4. In the framework of present knowledge, the idea is put forward that the structural unit forming the binding site for the AMP moiety of ATP in ATPases is similar to the structural unit forming the binding site for the AMP moiety of NAD and ADP in several dehydrogenases and kinases. PMID- 6250611 TI - On the structure of the hemocyanin channel in lipid bilayers. AB - Keyhole limpet hemocyanin has been shown by others (Alvarez, O., Diaz, E. and Latorre, R. (1975) Biochim. Biophys. Acta 389, 444-448) to form single conductance channels in black lipid membranes. In an attempt to visualize how the large (300 A) water-soluble hemocyanin molecule interacts with lipid bilayers, we have examined hemocyanin in the presence of lipids with the electron microscope. We find that incubation of lipids with keyhole limpet hemocyanin produces a characteristic 70 A in diameter, ring-shaped particle or annulus associated with the bilayer. This annulus, which appears to be quite distinct from previously observed aggregated and dissociated forms of hemocyanin, may be responsible for the channel formation in black lipid membranes. PMID- 6250612 TI - Potassium binding to the (Na+ + K+)-ATPase. AB - The number of K+ bound to the (Na+ + K+)-ATPase has been measured under equilibrium conditions by a differential-titration technique (Hastings, D.F. (1977) Anal. Biochem. 83, 416-432). 5.1 K+ were bound per 32P-labelling site. The K'D for K+ was dependent on the concentration of choline, which was included to give ionic strength. K'D was 59 +/- 2.5 microM with 97 mM choline, 26 +/-1.9 microM with 30 mM choline. The K+ : choline selectivity was 2564 : 1 and the calculated K'D for K+ with zero choline was 11 microM and for choline with zero K+ was 28 mM. 20 microM ATP in the presence of 97 mM choline incresed the K'D for potassium 3-fold to 177 +/- 14 microM. The K'D for K+ with 3 mM Na+ in the presence of 27 mM choline was 81 +/- 10 microM and with 30 mM Na+ without choline 700 +/- 250 microM. The calculated K'D for Na+ at zero K+ and zero choline was 0.6 +/- 0.2 mM. The K+ : Na+ selectivity was 54 : 1. PMID- 6250613 TI - Characterization of an endonuclease activity associated with Friend-murine leukemia virus. AB - An endonuclease activity shown to be associated with Friend leukemia virus has been characterized using double-stranded phi X174 DNA as substrate. In the presence of Mg2+, the endonuclease activity was able to convert supercoiled circular DNA duplexes to the relaxed form by introducing single-stranded nicks into the DNA. Most of the nicked DNA duplexes contained only one nick per strand, since unit length DNA was the predominant species obtained when the nicked DNA was analyzed by alkaline sucrose gradient centrifugation. The regions into which the nick could be introduced were evenly distributed around the circular DNA molecule. When Mn2+ was substituted for Mg2+ in the reaction mixture, the number of nicks introduced into circular DNA duplexes by the virus associated endonuclease was greatly increased. In contrast to circular duplexes, linear duplexes and single-stranded DNA functioned poorly as substrates for the virus associated enzyme. The Friend leukemia virus-associated endonuclease activity is with respect to these characteristics very similar to the endonuclease activity associated with the p32 protein of the avian myeloblastosis virus [1]. The molecular weight of the Friend leukemia virus endonuclease was estimated by gel filtration on a Sephacryl S-200 column to be about 45 000. PMID- 6250614 TI - Ionic control of enzymic degradation of double-stranded RNA. AB - The pattern of the degradation of various double-stranded polyribonucleotides by several ribonucleases (bovine RNAase A and its cross-linked dimer, bovine seminal RNAase, and pike-whale pancreatic RNAase) has been studied as a function of ionic strength and pH. It appears that (1) there is no direct correlation between the secondary structure of double-stranded RNA and its resistance against enzymatic breakdown, i.e., the stability of the secondary structure of double-helical RNA is not the main variable in the process. (2) The acstivity responses of the enzymes examined to changes of ionic strength and pH suggest that enzymic degradation of double-stranded RNA is mainly controlled by ion concentration, and that the process may fall within the phenomena interpreted by the theory of the ionic control of biochemical reactions advanced by Douzou and Maurel (Douzou, P. and Maurel, P. (1977) Proc. Natl. Acad. Sci. U.S.A. 74, 1013--1015). (3) The activity curves of the enzyme studied show, at a given pH, a shift toward higher ionic strengths as a function of the basicity of the enzyme protein. This finding explains the already observed correlation between number and/or density of positive charges of a ribonuclease molecule and its ability to attack double stranded RNA in 0.15 M sodium chloride/0.015 M sodium citrate (SSC). (4) A careful analysis of the influence of ionic strength and pH on the reaction appears to be necessary in order to characterize a ribonuclease which shows activity towards double-stranded RNAs, and to allow a meaningful comparison between different enzymes capable of attacking these substrates. PMID- 6250615 TI - In vitro replication of bacteriophage T7 DNA damaged by ultraviolet radiation. AB - The effect of ultraviolet radiation on DNA replication has been examined with an in vitro system capable of replicating intact chromosomes of T7 DNA from an exogenous template. Exposure of the template DNA to ultraviolet radiation resulted in a sharp drop in the amount of in vitro DNA synthesis. The residual replication detected when irradiated templates were used was found to proceed semiconservatively and to result in the production of pieces of duplex DNA approximately the same size as the average distance between pyrimidine dimers. It was also found that prior irradiation of the template inhibits formation of fast sedimenting concatemer-like DNA structures normally synthesized in vitro. Hybridization studies demonstrated that the product synthesized in vitro from ultraviolet-irradiated templates includes DNA from both the left and right halves of the T7 chromosome. This may mean that after ultraviolet irradiation more than one origin of replication exists. PMID- 6250616 TI - Restriction fragment primed phi X174 single-stranded DNA as template for DNA polymerase alpha and beta. Detection and partial purification of a polymerase alpha stimulating factor. AB - Template-primers constructed of phiX174 single-stranded viral DNA hybridized to a restriction fragment of phiX174 RF DNA can be used for extensive polymerization by DNA polymerase alpha. Polymerization is dependent upon a restriction fragment containing a 3'OH. The products of the reaction have been identified by agarose gel electrophoresis. Polymerization of 150--400 nucleotides can be obtained in 1h depending upon the restriction fragment used as primer. Synthesis may be limited by barriers in the primary or secondary structure of the template. A factor which stimulates the rate of alpha polymerase activity on these templates was partially purified. This factor does not stimulate alpha polymerase on activated DNA. The stimulating factor sediments at 5.5 S in glycerol gradients containing 0.4M potassium phosphate and has an apparent molecular weight of 70 000 on Sephadex G 100. PMID- 6250617 TI - Inhibition of herpes simplex virus-induced DNA polymerase, cellular DNA polymerase alpha, and virus production by aphidicolin. PMID- 6250618 TI - Properties of herpes simplex virus type 1 and type 2 DNA polymerase. AB - Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) DNA polymerases were highly purified from infected HeLa BU cells by DEAE cellulose, phosphocellulose and DNA cellulose column chromatography. DNA exonuclease activity but not endonuclease activity was found associated with both types of DNA polymerase. Both DNA polymerase activities could be activated by salt in a similar fashion with the optimal activity in the range of ionic strength between 0.22 and 0.29 alpha. At an ionic strength of 0.14, spermidine and putrescine in the concentration range (0--5 mM) studied could mimic the action of KCI in stimulating DNA polymerase activity. Spermine, in the same concentration range, had a biphasic effect. At an ionic strength of 0.29 all three polyamines were inhibitory. HSV-1 and HSV-2 DNA polymerase are similar in their column chromatographic behavior, sedimentation rate in sucrose gradient centrifugation, and activation energy, but they differ in their heat stability at 45 degrees C with the HSV-2 enzyme more stable than the HSV-1 enzyme. Kinetic behavior of both enzymes is similar, with Km values for deoxyribonucleoside triphosphates in the range of 5 . 10(-7) to 1.8 . 10(-8) M. IdUTP and dUTP served as apparent competitive inhibitors with respect to dTTP, and AraATP acted as an apparent competitive inhibitor with respect to dATP. AraATP could not replace dATP in the DNA polymerization reaction; in contrast, IdUTP could replace TTP. Phosphonoformic acid behaved as an uncompetitive inhibitor with respect to DNA. The ID(50) value estimated was foind to be dependent on the purity of the DNA polymerase used and the ionic strength of the assay condition. Each DNA polymerase associated DNA exonuclease had the same stability at 45 degrees C as its DNA polymerase. The associated DNAase activity was inhibited by phosphonoformic acid and high ionic strength of the assay condition. PMID- 6250619 TI - The DNA polymerase beta reaction with ultraviolet-irradiated DNA incised by correndonuclease. AB - Covalently closed circular Col E1 DNA was ultraviolet-irradiated with a dose of 60 J/m2, thus introducing about 3.2 pyrimidine dimers per DNA molecule. Treatment of irradiated Col E1 DNA with Micrococcus luteus correndonuclease resulted, in the vicinity of pyrimidine dimers, in an average of 3.3 incisions per DNA molecule, and converted DNA to the open circular form. Incised Col E1 DNA stimulated no reaction with calf thymus DNA polymerase alpha but was recognized as a template by DNA polymerase beta. The latter enzyme incorporated about 1.6 molecules of dTMP (corresponding to 6 molecules od dNMP) per one correndonuclease incision. The length of the DNA polymerase beta product was comparable to the anticipated length of the DNA region within which the hydrogen bonds were disrupted owing to dimer formation. The enzyme required Mg(2)=nd four dNTPs for reaction and was resistant to N-ethylmaleimide or p-mercuribenzoate. The average numbers of deoxynucleotides incorporated per one DNAase I incision or per one nonspecific break, measured in control samples, were equal, amounting to 0.3 dTMP molecule. This value corresponded to 1.2 dNMP molecule; in our opinion, this reflects contaminating nuclease activity of the system used. The present results testify to the ability of DNA polymerase beta to repair synthesis by the "patch and cut' mechanism. PMID- 6250620 TI - Biogenesis of mitochondria. Two-dimensional electrophoretic analysis of mitochondrial translation products in yeast. AB - 1. Mitochondrial translation products of yeast Saccharomyces cerevisiae were separated according to charge as well as molecular weight by a highly resolving two dimensional electorphoretic technique (isoelectric focusing in the first dimension ana SDS-electrophoresis in the second dimension). 2. The major protein components (the oligomeric form of subunit 9 of mitochondrial ATPase, var 1, cytochrome oxidase subunits I, II and III, subunit 6 of mitochondrial ATPase and cytochrome b apoprotein) were identified either from their mobility in SDS electrophoresis or by using mit- mutants defective in certain mitochondrially made polypeptides. 3. This method allowed the separation of subunit III of cytochrome oxidase and subunit 6 of mitochondrial ATPase which cannot be resolved by conventional SDS-polyacrylamide gel electrophoresis. 4. Subunit II of cytochrome oxiodase resolves in two spots of similar pI values and subunit 6 of mitochondrial ATPase resolves in two spots of similar molecular weight. In both cases the double spots disappear simultaneously following a single mutation in the coresponding structural gene. 5. Total mitochondrial proteins were also resolved two-dimensionally revealing over 100 components. The mitochondrial translation products, with the exception of subunit 9 of mitochondrial ATPase, could be easily recognized among the other mitochondrial proteins. PMID- 6250621 TI - AUG is the only initiation codon in eukaryotes. AB - An analysis of mutants of the yeast Saccharomyces cerevisiae indicates that AUG is the sole codon capable of initiating translation of iso-1-cytochrome c. This result with yeast and the sequence results of numerous eukaryotic genes indicate that AUG is the only initiation codon in eukaryotes; in contrast, results with Escherichia coli and bacteriophages indicate that both AUG and GUG are initiation codons in prokaryotes. The difference can be explained by the lack of the t6 A hypermodified nucleoside (N-[9-(beta-D-ribofuranosyl)purin-6 ylcarbamoyl]threonine) in prokaryotic initiator tRNA and its presence in eukaryotic initiator tRNA. PMID- 6250622 TI - Purification and some properties of inducible N-acetylglucosamine kinase from Candida albicans. AB - N-Acetylglucosamine kinase (ATP:2-acetamido-2-deoxy-D-glucose 6 phosphotransferase, EC 2.7.1.59) catalyzes the first reaction in the inducible N acetylglucosamine catabolic pathway of Candida albicans, an obligatory aerobic yeast. As a part of continuing biochemical studies concerning the regulation of gene expression in a simple eukaryote, N-acetylglucosamine kinase has been purified and characterized biochemically. The enzyme has been purified about 300 fold from the crude extract and its molecular weight of 75 000 has been determined by Sephadex G-100 gel filtration. Isolation and analysis procedures are described. The kinase reaction is optimal within a pH range of 7--8. The enzyme is strictly specific for GlcNAc as phosphate acceptor; ATP is the phosphoryl group donor for the kinase reaction and to a lesser extent dATP and CTP. Km values for GlcNAc and ATP are 1.33 mM and 1.82 mM, respectively. The enzyme required Mg2+, which may be replaced by other bivalent metal ions such as Mn2+, Ca2+, Ba2+ and Co2+ for a lesser degree of effectiveness. The purified enzyme is extremely sensitive to thermal denaturation and becomes completely inactive by heating at 65% C for 2 min. The enzyme is also inactivated by sulphydryl reagents such as p-chloromercuribenzene sulfonic acid and N ethylmaleimide. PMID- 6250623 TI - Apparent 'glucokinase' activity in non-hepatic tissues due to N-acetyl-D glucosamine kinase. AB - 1. Electrophoretic examination of tissue extracts from rat intestinal mucosa, kidney, lung, spleen, mammary gland, adipose tissue, heart muscle and placenta in agarose gels did not reveal the presence of any glucokinase (ATP:D-glucose 6 phosphotransferase, EC 2.7.1.2) activity corresponding to that present in rat liver. 2. All these tissues do contain an enzyme that possesses very high-Km glucose-phosphorylating activity but which has a slightly lower electrophoretic mobility than glucokinase and can be separated from it by various means. 3. This phosphotransferase activity is due to N-acetyl-D-glucosamine kinase (ATP:2 acetamido-2-deoxy-D-glucose 6-phosphotransferase, EC 2.7.1.59), which has been partialyy purified from intestinal mucosa tissue and shown to have similar kinetic properties to the same enzyme previously purified more extensively from liver and kidney. 4. It is suggested that many of the effects reported in the literature of 'glucokinase' activity in non-hepatic tissues are probably due to N acetyl-D-glucosamine kinase. PMID- 6250624 TI - Inhibition of UDP-N-acetylglucosamine pyrophosphorylase by uridine. AB - UDP-N-acetylglucosamine pyrophosphorylases (UTP: 2-acetamido-2-deoxy-alpha-D glucose-1-phosphate uridylyltransferase, EC 2.7.7.23) from baker's yeast and Neurospora crassa IFO 6178 were inhibited by uridine which is the nucleoside moiety of UDP-GlcNAc. The inhibition was shown in both directions of pyrophosphorolysis and of synthesis of UDP-GlcNAc. Kinetic analysis revealed that uridine demonstrated a noncompetitive type of inhibition with UDP-GlcNAc and competitive inhibition with PPi. The Ki values for the baker's yeast enzyme were 1.8 mM for UDP-GlcNAc and 0.16 mM for PPi, and the values for the Neurospora enzyme were 1.1 mM for UDP-GlcNAc and 0.15 mM for PPi, respectively. Uridine did not bind irreversibly to the enzyme, as the activity was restored with dialysis. No other nucleosides caused inhibition of the enzyme activity except uridine. Some uridine derivatives, such as 5-hydroxyuridine, 5,6-dihydrouridine and pseudouridine, also inhibited the enzyme activity. But doexyuridine showed only slight inhibition, and 5'-UMP and orotidine caused no inhibition of the enzyme activity. PMID- 6250625 TI - [Effects of basic proteins of low molecular weight on the phosphohydrolase and phosphotransferase activities of microsomal glucose-6-phosphatase in adult monkey hepatocytes (author's transl)]. AB - The effects of histone 2A and some polycations on microsomal carbamylphosphate:D glucose phosphotransferase and glucose-6-phosphate phosphohydrolase activities (D glucose-6-phosphate phosphohydrolase, EC 3.1.3.9), have been investigated. 1. Histone 2A and polycations activate the two enzymic activities. At a constant cation concentration, this activation increases with the number of cationic groups per molecule. 2. Activation by histone 2A is related to its fixation on microsomal membranes. This fixation varies with quantities of histones and pH. 3. The nature of the interactions between histones and microsomal membranes is shown to be electrostatic, probably between the cationic groups of histones and the anionic group of membranous lipids. 4. Kinetic analysis reveal that histone 2A increases the maximal reaction velocity but does not affect the apparent Michaelis constant values for the substrates. 5. The role played by the cationic groups of histone 2A on the microsomal glucose 6-phosphatase, is discussed. PMID- 6250626 TI - Purification of human liver fructose-1,6-bisphosphatase. AB - Human liver fructose-1,6-bisphosphatase (D-fructose-1,6-bisphosphate 1 phosphohydrolase, EC 3.1.3.11) has been purified 1200-fold using a heat treatment step followed by absorption on phosphocellulose at pH 8 and specific elution with buffer containing the substrate (fructose 1,6-bisphosphate) and allosteric effector (AMP). The enzyme is homogeneous in electrophoresis in polyacrylamide gel, in the presence and absence of denaturing agent. It has a molecular weight of 144 000 and is composed of four identical or nearly identical subunits. Fluorescence spectra indicate that the enzyme does not contain tryptophan residues. The pH optimum is 7.5 and the Km is determined as 0.8 microM. The enzyme is inhibited by AMP in cooperative manner with a K0 x 5 of 6 microM. PMID- 6250627 TI - Use of fluoride to inactivate phosphorylase a phosphatases from rat liver cytosol. Presence of fluoride-insensitive glycogen synthase-specific phosphatase. AB - The diverse metal requirements for activity of the phosphoprotein phosphatases (EC 3.1.3.16) concerned with glycogen metabolism in rat liver were postulated to reflect the diverse binding intensities of their essential metal(s). After inactivation by fluoride, three of these phosphatases had similar metal requirements in contrast to a fourth phosphatase. Further similarities led to a grouping of these enzymes into two general types. Phosphatases designated type 1 consisted of three enzymes which had the following properties; (1) preference for glycogen phosphorylase a as a substrate; (2) molecular weights in excess of 100 000; (3) conversion to an active 30 000 dalton 'subunit' form upon selective denaturation by 80% ethanol; (4) diverse degrees of stimulation by metals (Mg2+ and Mn2+); and (5) changes to an absolute dependence upon added Mn2+ (but not Mg2+) for activity of both the holoenzyme and the subunit after a demetallating treatment with fluoride in EDTA. The phosphatase designated type 2 exhibited the following properties; (1) preference for glycogen synthase D as a substrate; (2) molecular weight of 50 000; (3) no conversion to an active 30 000 dalton subunit form upon selective denaturation by 80% ethanol; (4) complete metal-dependence upon either Mg2+ or Mn2+; and (5) no change to an absolute dependence on added Mn2+ for activity after a demetallating treatment with fluoride in EDTA. PMID- 6250628 TI - Studies on the properties of a soluble phosphatidylinositol-phosphodiesterase of rabbit iris smooth muscle. AB - Some properties of the soluble phosphatidylinositol phosphodiesterase (monophosphatidylinositol inositolphosphohydrolase, EC 3.1.4.10) of rabbit iris smooth muscle are described. Studies on its subcellular distribution showed that in this tissue the phosphodiesterase is not exclusively cytosolic. Thus, under our experimental conditions about 58% of the enzyme activity was found in the soluble fraction and the remainder was particulate. When the latter was treated with deoxycholate about 59% of the enzyme activity, compared to 86% of that of ATPase, was still bound to the particulate fraction. The kinetic properties of the enzyme (30--50% (NH4)2SO4 fraction) were examined. Maximum breakdown was 7.7 mumol/h per mg protein and occurred at pH 5.6. The products of [14C]arachidonic acid-labelled phosphatidylinositol were 1,2-diacylglycerol and a mixture of 86% myoinositol 1-phosphate and 14% myoinositol 1,2-(cyclic)phosphate. The enzyme has an absolute requirement for Ca2+. Addition of Ba2+, La3+, Mg2+, Mn2+, EGTA or EDTA at 0.05--5 mM concentrations; Sr2+ at higher concentrations (greater than 0.25 mM) markedly inhibited the phosphodiesterase activity and this inhibition was completely reversed by Ca2+. The enzyme is specific for the phosphoinositides. PMID- 6250629 TI - The oxygen-dependent deactivation and reactivation of spinach ribulose-1,5 bisphosphate carboxylase. AB - Ribulose-1,5-bisphosphate carboxylase-oxygenase (3-phospho-D-glycerate carboxy lyase (dimerizing), EC 4.1.1.39) is deactivated by the removal of oxygen, and reversibly reactivated by its readdition to the enzyme solution. A short pulse of oxygen to the anaerobic enzyme solution is sufficient to trigger the reactivation process; the Ka value for this reaction was estimated as 0.12 mM oxygen. The enzyme could not be reactivated under anaerobic conditions by an organic oxidant (benzoylperoxide) or by sulfhydryl group reducing reagents (dithiothreitol or beta-mercaptoethanol), suggesting that the process of reactivation was oxygen specific. Furthermore, the inhibition of the reactivation by superoxide anion scavengers such as Tiron (1,2-dihydroxybenzene-3,5-disulfonic acid), copper penicillamine, hydroxylamine, nitroblue tetrazolium, and ascorbate, indicated that the monovalent reduced oxygen was involved as the reacting species in this process. The deactivation of the enzyme associated with the removal of oxygen was also sensitive to the presence of scavengers of O2(-), suggesting that superoxide anion was also involved in the deactivation process. Both the carboxylase and the oxygenase activities were similarly affected under all the experimental conditions studied. On the basis of these results it is argued that the enzyme molecules are able to reduce oxygen and that superoxide anion causes the deactivation or reactivation of the enzyme. PMID- 6250630 TI - Hormone-sensitive lipase of rat adipose tissue: correlation of activity with a protein of molecular weight 84 000. AB - Hormone-sensitive lipase of rat adipose tissue was partially purified. The enzyme retained its capacity to be activated by cyclic AMP-dependent protein kinase throughout purification. When the partially purified 32P-labeled preparation was subjected to two-dimensional gel electrophoresis, the enzyme activity was found to be associated with a 32P-labeled protein of molecular weight 84 000. The result suggests that this 32P-labeled protein represents hormone-sensitive lipase or the catalytic subunit of the enzyme. PMID- 6250631 TI - Purification and properties of retinol- and retinoic acid-binding proteins from a transplantable mouse colon tumor. AB - Cellular retinol-binding protein and retinoic acid-binding protein, the possible mediators of the action of retinoids in epithelial differentiation and control of tumorigenesis, have been reproducibly purified from mouse colon tumor 26, and some of their properties were studied. The main steps of purification involved acid-precipitation, DEAE-Sephadex, CM-cellulose and Sephadex G-100 chromatography. About 2 mg of the binding proteins were isolated from 60 g tumor. The purified preparations showed only two protein bands on polyacrylamide gel electrophoresis. The two binding proteins were partially resolved by sedimentation equilibrium technique; but was completely separable by preparative electrophoresis in the presence of sodium dodecyl sulfate. The retinol- and retinoic acid-binding proteins are presumably monomers with molecular weights of 15,500 and 14,600, respectively, as determined by polyacrylamide gel electrophoresis in sodium dodecyl sulfate. On gel filtration however, both the binding proteins retarded to the same molecular size of 17,800. On preparative columns, both the proteins expressed the same isoelectric pH, 4.5. Both proteins of the tumor possessed functional thiol groups. The mercurial inhibition of the binding capacity of the proteins for their ligands was reversible upon treatment with thiol compounds. PMID- 6250632 TI - EPR spectroscopy of soybean lipoxygenase-1. Determination of the zero-field splitting constants of high-spin Fe(III) signals from temperature and microwave frequency dependence. AB - The zero-field splitting constants (D) of the different components building up the high-spin Fe(III) EPR spectrum of lipoxygenase from soybeans were determined by two methods: (1) temperature dependence studies using the low-spin Fe(III) signal of cytochrome c at g 3 for accurate measuring of the temperature in the sample; (2) by establishing g-shift upon increasing the microwave frequency. The ranges of D for the axial and rhombic species contributing to the complex signal at g 6 are found to be 1.5-3.0 K and 1.8-4.4 K, respectively. The occurrence of such large ranges is attributed to variations in amount and number of species in the different samples. The combination of the applied methods offers a more generally applicable approach to the determination of zero-field splitting constants. PMID- 6250633 TI - Circular dichroism comparative studies of two bacterial collagenases and thermolysin. AB - The recently isolated and purified collagenase produced by Achromobacter iophagus, the collagenase from Clostridium histolyticum, and thermolysin, three enzymes having common properties, were studied by circular dichroism. From the spectra of the aqueous solutions obtained in the peptide region, the fraction of alpha helix, beta sheet and aperiodic segments in the three proteins could be estimated. Good similarity was found between Achromobacter collagenase and thermolysin, which both contain a high fraction of alpha helix. Side-chain contributions were analyzed in the aromatic region of thespectra: effects of pH and of organic solvents were observed, showing the strong influence of surroundings on the stabilization of the proteins. PMID- 6250634 TI - Evidence for the absence of photoreduction of the metal centers of cytochrome C oxidase by X-irradiation. AB - Samples of X-irradiated cytochrome c oxidase were examined by electron paramagnetic resonance and optical spectroscopy. Both radiation from the Stanford Synchrotron Radiation Laboratory and a conventional X-ray source (W target) were utilized. The X-ray flux from these sources ranges from 10(9) to 10(13) photons/s. No evidence was found for photoreduction of the metal centers in the enzyme by X-ray photons. These results demonstrate that the integrity of cytochrome c oxidase is maintained using the conditions under which X-ray absorption measurements are presently being made. PMID- 6250635 TI - Structure of Cu2(indomethacin)4 and the reaction with superoxide in aprotic systems. AB - The copper complex of indomethacin (1-(p-chlorobenzoyl)-5-methoxy-2-methyl-indole acetate), a common anti-inflammatory drug, was prepared and characterized. Crystal structure determination revealed the dimeric form of the 1 : 2 complex, namely Cu2(indomethacin)4 x L2, in the unit cell. Surprisingly, the copper-copper distance (263 pm) was very close to metallic copper (256 pm). The two coordination sites in the copper-copper axis can be readily replaced by superoxide. An intriguing similarity to Cu2(acetate)4 was seen. Due to the lipophilic nature of the indomethacin ligand, this copper complex reacted with superoxide in aprotic solvents. the superoxide dismutating activity was successfully demonstrated in Me2SO/water and acetonitrile/water mixtures using the nitro-blue tetrazolium assay and pulse radiolysis. The second-order rate constant of 6 x 10(9) M-1 x s-1 in strictly aqueous systems dropped only slightly to 1.1 x 10(9) M-1 x s-1 when aprotic solvents were used. This is the fastest rate constant ever observed for a copper-dependent dismutation of superoxide. The KO2-induced lipid peroxidation in both erythrocytes and liver microsomes was suppressed by 70% in the presence of 1 x 10(-10) mol x ml-1 of Cu2(indomethacin)4. The inhibitory action dropped to 25% when Cu2Zn2superoxide dismutase was employed. The formation of copper x indomethacin in rat serum after administration of indomethacin was shown in vitro and vivo. PMID- 6250636 TI - Epinephrine effects on cyclic AMP-dependent protein kinases from rat diaphragms. AB - Diaphragm extracts were subjected to electrophoresis on polyacrylamide gels to separate the different molecular species of th cyclic AMP-dependent protein kinase. Using cyclic [3H]AMP, three peaks of binding activity were observed. The peak closest to the origin (peak I) was associated with cyclic AMP-dependent protein kinase activity and was abolished by incubation of the extracts with cyclic AMP prior to electrophoresis. The peak farthest from the origin (peak III) was devoid of kinase activity and was increased by incubation of extracts with cyclic AMP before electrophoresis; furthermore, when extracts were incubated with cyclic [3H]AMP before electrophoresis, essentially all the radioactivity appeared in peak III. Peak II, in an intermediate position, was also abolished by preincubation of the extracts with cyclic AMP and both its binding capacity and cyclic AMP-dependent protein kinase activity were lower than in Peak I. A peak of cyclic AMP-independent protein kinase (peak 0) that migrated more slowly than peak II was also detected. From these and other data it is concluded that peaks I and II are cyclic AMP-dependent protein kinase and that peak III is the dissociated regulatory subunit, respectively. Peak 0 is cyclic AMP-independent protein kinase together with free catalytic subunits from cyclic AMP-dependent protein kinase. Incubation of rat diaphragms with epinephrine resulted in dose- and time-dependent decrease in peak I and increase in peak III. These changes correlated with the decrease of cyclic AMP-dependent protein kinase associated with peak I. No changes in Peak II were observed with epinephrine, but an increased peak 0 was noted. Changes in peak I and peak III correlated with the modification of glycogen synthase and glycogen phosphorylase activities. No regulatory subunits (peak III) were detected as phosphorylated forms in diaphragms previously equilibrated with 32P. Treatment with epinephrine produce no noticeable phosphorylation of these regulatory subunits. PMID- 6250637 TI - Dibutyryl cyclic AMP affects hyaluronate synthesis and macromolecular organization in normal adult articular cartilage in vitro. AB - When normal adult dog articular cartilage was cultured in the presence of dibutyryl cyclic AMP a higher proportion than normal of newly synthesized 35S labeled glycosaminoglycans was released from the tissue into the culture medium, although their net synthesis was not affected. In conjunction with this release of sulfated glycosaminoglycans, 24 times more [3H]glucosamine-labeled hyaluronic acid was released from the cartilage into the medium, and net hyaluronate synthesis was enhanced 3-fold. Virtually all of the newly synthesized hyaluronic acid in the medium was associated with proteoglycans. The proteoglycans in the medium of the dibutyryl cyclic AMP treated cultures were normal in hydrodynamic size and interacted normally with hyaluronic acid to form large aggregates. These results suggest that the increase in hyaluronate synthesis caused by dibutyryl cyclic AMP mayt have destabilized the interaction of proteoglycans with the collagen meshwork of the cartilage. The changes seen in normal adult articular cartilage after incubation with dibutyryl cyclic AMP, therefore, are similar to those which are observed in cartilage of osteoarthritic joints. PMID- 6250638 TI - Negative cooperativity of rat kidney beta-adrenergic receptors. PMID- 6250639 TI - Comparative studies on superoxide anion production by polymorphonuclear leukocytes stimulated with various agents. AB - Guinea-pig peritoneal polymorphonuclear leukocytes promoted superoxide anion (O2( )) generation when stimulated with soluble antigen-antibody complex, concanavalin A or sodium dodecyl sulfate. The enhancement with antigen-antibody complex or concanavalin A was inhibited with diisopropyl fluorophosphate. On the other hand, the enhancement with sodium dodecyl sulfate was not affected by the inhibitor. L 1-pTosylamido-2-phenylethyl chloromethyl ketone (Tos-PheCH2Cl) and tetrahydrofuran also enhanced O2(-) generation even in the presence of diisopropyl fluorophosphate, while at low concentrations they inhibited O2(-) generation with antigen-antibody complex. These results indicate that a certain diisopropyl fluorophosphate-sensitive factor may be involved in the O2(-) generating response of leukocytes to antigen-antibody complexes or concanavalin A, but not in that to sodium dodecyl sulfate, Tos-PheCH2Cl or tetrahydrofuran. PMID- 6250640 TI - Effect of insulin and prednisolone on cyclic nucleotides and phosphoenolpyruvate carboxykinase activity in brown fat and liver of developing rats. AB - The concentrations of cyclic AMP and cyclic GMP in brown fat and liver of both suckling and adult rats at fixed times after injection of insulin (2.5 U/100 g body weight) or prednisolone (2.5 mg/100 g body weight) were compared with the activity of phosphoenolpyruvate carboxykinase assayed 24 h after the injections. A stimulus that produced an increase in cyclic AMP content also produced an increase in the enzyme activity. If the content of cyclic GMP was also increased there was no rise in phosphoenolpyruvate carboxykinase activity. A rise in the content of cyclic GMP alone was associated with a reduction in the activity of the enzyme. These preliminary results indicate that cyclic AMP could be involved in the induction of phosphoenolpyruvate carboxykinase and that cyclic GMP may somehow be related to its repression. The known differences in the response of phosphoenolpyruvate carboxykinase activity to insulin and prednisolone in different tissues and at different stages of ontogenic development may thus be linked to differences in the responsiveness of enzymes concerned with the metabolism of cyclic nucleotides. PMID- 6250641 TI - Growth hormone and insulin binding to isolated hepatocytes in the genetically dwarf mouse. AB - The interaction of growth hormone with its specific receptors in dwarf mice was investigated. (1) The interaction of 125I-labeled human growth hormone with isolated mouse liver cells is a specific, time-dependent and saturable process. Hepataocytes of male and female dw/dw mice bound only 10-20% as much growth hormone per unit of cell surface area as those of their litter mates. Scatchard analysis suggested that this decrease in binding was due to a decreased number of receptor sites in th liver cell of the dwarf mouse. (2) In contrast to the marked decrease in growth hormone receptors, the binding of insulin is higher in dwarf mice than in litter mates, at low hormone concentration. (3) Competition and stoichiometric studies indicate that growth hormone and prolactin bind to the same type of binding site in female and male mouse hepatocytes. These results indicate that dwarfism in this animal was associated with a loss in the number of growth hormone binding sites. The decrease in growth hormone receptors and the increase in insulin receptors correlate well with the respective biological activity of these two hormones. PMID- 6250642 TI - Esterification of cholesterol and lipid-soluble vitamins by human pancreatic carboxyl ester hydrolase. AB - Human pancreatic carboxyl ester hydrolase is shown to catalyse the esterification of cholesterol and lipid-soluble vitamins A, E and D3 with oleic acid. The acitivity requires the presence of bile salts, and the trihydroxylated or the 3 alpha, 7 alpha dihydroxylated bile salts are better activators than the 3 alpha, 12 alpha dihydroxylated bile salts. The hydrolyzing and synthetizing activities of human pancreatic carboxyl ester hydrolase are separated by a large pH range since the synthesis of cholesterol esters is optimal at pH 5.25 and the hydrolysis of cholesterol and vitamin E esters is optimal at pH 8.0. From the comparison of the catalytic constants determined for the hydrolyzing and synthetizing activities and from the pH dependence of the two activities, it appears that human carboxyl ester hydrolase plays an important part in the intestinal lumen. The role of the enzyme in the esterification of cholesterol and lipid-soluble vitamins is questionable. PMID- 6250643 TI - [Effect of ouabain on the lactogenic action of prolactin and on the level of mammary prolactin receptors]. AB - Ouabain added to the culture medium of rabbit mammary gland inhibits prolactin action on the initiation of lactose and casein synthesis. The degree of inhibition is a function of the ouabain concentration in the medium. Likewise, ouabain blocks the accumulation of casein mRNA supported by prolactin. In addition, ouabain provokes a rapid disappearance of prolactin receptors. Conversely prolactin keeps its capacity to enhance the concentration of casein mRNA and the parallel casein synthesis when K+ ions are totally absent from the culture medium. These results suggest that although prolactin induces a modification of the K+/Na+ ratio in the mammary cell and ouabain prevents this effect of prolactin, the inhibitory action of ouabain on lactogenesis can be explained essentially by its effect on the hormone receptors. PMID- 6250644 TI - Irreversible inactivation of beta-adrenergic receptors of C6 glioma cells. Synthesis and study of a thiol derivative of propranolol. AB - The beta-adrenergic receptor of C6 glioma cells contains a disulfide bridge which can be reduced by dithiothreitol (DTT). On intact cells, N-ethylmaleimide (NEM) (5 mM) does not change the affinity of [3H] H2-alprenolol ([3H] DHA) but reduces the total number of beta-adrenergic cell receptors by 21 +/- 3 per cent ; (N = 3). After receptor reduction by DTT, NEM irreversibly blocks the accessibility of the beta-adrenergic receptors to [3H]DHA. On isolated membranes, incubation in the presence of either NEM (5 mM) or isoproterenol (5.10(-7) M) does not significantly modify the total number of beta-adrenergic receptors accessible to [3H]DHA. Incubation of membranes with both NEM and isoproterenol reduces the number of binding sites by 33 +/- 2 per cent ; (N = 3). A thiol derivative of propranolol was synthetized. Its affinity is 10 times lower than that of propranolol. This sulfur derivative reduces the total number of beta-adrenergic receptors by 22 +/- 3 per cent (N = 3) when incubated with the native receptor and by 55 +/- 4 per cent (N = 4) when incubated with the reduced receptor. DTT does not significantly reverse the blockade induced by propranolol-SH. A model is proposed for explaining these results. PMID- 6250645 TI - [Ubiquinone reduction, proton absorption and the formation of a transmembrane electric potential differential induced by a series of light bursts in the chromatophores of Rhodopseudomonas sphaeroides]. PMID- 6250646 TI - [Photosensitivity of cytochrome C conformational states at different pH values]. PMID- 6250647 TI - The effect of exogenous steroids and steroid inhibitors on IgG transmissions in young rats. AB - The transmission of labelled IgG by the proximal small intestine was assessed in 16- and 18-day-old rats. Closure had commenced by 18 days and in some animals was well advanced by this age. The injection of large doses of cortisone acetate, hydrocortisone sodium succinate, deoxycorticosterone acetate and corticosterone induced precocious closure of the small intestine by 16 days; and all but the latter steroid also induced precocious cell replacement in the ileum. Maternal deprivation for about 18 h daily led to closure of the proximal small intestine but did not induce precocious replacement in the ileum. The injection of metopirone, aminoglutethimide and ACTH resulted in partial closure of the proximal small intestine but did not induce precocious cell replacement in the ileum. Maternal deprivation for about 8 h daily produced a similar result. PMID- 6250649 TI - The mitochondrial membrane potential. PMID- 6250650 TI - Regulation of the contact behaviour of cells. PMID- 6250648 TI - Iris pigmentation and fractionated reaction and reflex time. AB - Recent investigations indicate that an iris pigmentation-motor behavior exists, but may be limited to the reaction time component of a motor task. The absence of differences in peripheral nervous conduction (Wolf and Landers, 1978) suggests that a central nervous system mechanism may be operating, possibly dependent on the characteristics of neuromelanin or catecholamine turnover. Experiment 1 tested this notion by fractionating simple reaction time into the premotor and motor components by electromyography. ANOVA revealed that dark-eyed subjects had faster total reaction times and premotor times, but only the premotor time component approached significance (p < 0.07). Experiment 2 fractionated patellar reflex time of light-eyed and dark-eyed subjects into reflex lagency and motor components. There were no eye color differences for any of the reflex time measures. The results of Experiments 1 and 2 support a central nervous system explanation for the iris pigmentation-reaction time phenomenon. PMID- 6250651 TI - Urinary glycolipids of YC8 lymphoma bearing mice: effectors of glycosylation process. AB - Glycolipids from YC8 lymphoma bearing mice urines have peen obtained by the method of Folch and fractionated on silicic column and on silica gel plates. One fraction, among the five obtained, may be used by sera galactosyltransferase as an acceptor for galactose, to form a new glycolipid compound. Furthermore this fraction has shown an inhibitory effect on phosphatase activity, in agreement with hypothesis which relates relates glycosyltransferase and phosphatase activities during tumorous process. PMID- 6250652 TI - Dynamic light scattering studies of ribonuclease. AB - Dynamic light scattering has been used to measure the translational diffusion coefficients of bovine pancreatic ribonuclease A as functions of temperature and concentration in the presence of 1 M Guanidine-HCl. Data was collected throughout a temperature range including the folding-unfolding transitions. Evidence of a pretransition "swelling" of the protein was observed. Entropy and enthalpy changes upon unfolding were obtained using a two-state model. PMID- 6250653 TI - [Cyclic 3',5'-adenosine monophosphate in macrophages, intestinal mucosa, and blood plasma of germ-free and ordinary animals]. AB - The level of cAMP in macrophages, intestinal mucosa and blood plasma as well as its formation in intestinal mucosa of germfree animals under the effect of lipopolysaccharide E. coli 055 (LPS) were studied in experiments on germfree and ordinary mice and guinea-pigs. The concentration of cAMP in intestinal mucosa of ordinary guinea-pigs was 5-fold higher than in germfree animals. LPS induced an increase in cAMP level in intestinal mucosa, but this level did not reach that in ordinary animals. The levels of cAMP in blood plasma of germfree guinea-pigs in macrophages of germfree mice increased 2-fold and 4-fold, respectively, 30 minutes following the treatment with LPS. The increased level of cAMP was accompanied by its intensive secretion into the exocellular medium. Macrophages of ordinary animals had a moderate output of cAMP. A conclusion is made about the relationship between cAMP formation and microbial contamination of the microorganism as well as about an important role of the cyclic nucleotide in the mechanism of nonspecific resistance and homeostatic reactions of the body to microbial exposure. PMID- 6250654 TI - [Age and the effect of adrenocorticotropic hormone on aldosterone secretion in rats]. AB - Age-related changes in functional activity of the glomerular zone were studied in the adrenal cortex of Wistar rats. It was shown that secretion of the basic mineralocorticoid hormone aldosterone was decreased with age. The glomerular zone of old rats showed the reduced sensitivity to the stimulant action of corticotropin, marked by the pronounced reaction to less doses of the hormone administered. At the same time the reactivity and the range of shifts in the course of ACTH dosage build-up decrease with aging. PMID- 6250656 TI - [Effect of L-DOPA on cyclic adenosine-3',5'-monophosphate in neurogenically damaged cardiac muscle]. AB - During electric stimulation of the aortal reflexogenic zone in rabbits, administration of L-DOPA prevented the reduction of the level of cyclic adenosine 3',5'-monophosphate (cAMP) in the cardiac muscle and blood plasma. This is likely to be related to L-DOPA ability to participate in the biosynthesis of endogenous catecholamines, and thus to stimulate the synthesis of cAMP. PMID- 6250655 TI - [Effect of amizil and arecoline on the interaction of Na+ and Ca2+ ons in the cerebral nerve endings of rats]. AB - A study was made of the effect of the central cholinolytic benactizin and cholinomimetic arecoline on the uptake of 45Ca and 22N by rat brain synaptosomes. It was shown that benactizin in a dose of 40 mg/kg increased the incorporation and uptake of 45Ca and decreased the incorporation and uptake 22Na. Arecoline (2.5 mg/kg) increased the accumulation of 22Na and decreased the content of 45Ca in the synaptosomes. It is assumed that benactizin activates Ca-channels and inactivates Na-K-channels and inhibits or produces no action on Ca-channels. PMID- 6250657 TI - [Membrane antigens of transformed and tumor cells of hamsters]. AB - Normal membrane antigens to tumour and in vitro transformed tissue cultures of Syrian hamster cells were comparatively studied in cross-adsorption experiments. It was found that each cell strain has an individual profile of normal membrane antigens with characteristic quantitative and qualitative features seen on antigen expression. The absence of at least one of the antigens which the cells of other strains possessed was demonstrated with reference to the cells of each line tested. All 5 tumor cell lines were bearing antigen or a group of antigens absent on normal embryonic hamster cells (HE) and 5-strains of in vitro transformed HE cells. PMID- 6250658 TI - [Dynamics of the reactions of small intestine vessels of animals at the high altitudes]. AB - In acute experiments on cats carried out in Frunze (at an altitude of 760 m above the sea level, control group) and at the Touya-Ashu high-altitude base (3200 m above the sea level, Central Tien Shan), resistography and extracorporeal vein reservoir were used to study the reactions of resistance and capacitance blood vessels of the small intestine to intraarterial injection of adrenaline (0.5, 5 and 10 micrograms). The reactions were studied days 3, 15 and 30 after the animals stay in the mountains. It was found that during adaptation to extreme high-altitude conditions, the animals showed significant changes in the reactivity of alpha- and beta-receptors of smooth muslce cells, with these changes being inconsistent in the resistance and capacitance compartments of the small intestine. PMID- 6250659 TI - [Applicability of the integral form of the Michaelis-Menten equation for the kinetic study of transport ATPases]. AB - Applicability of the integrated form of the Michaelis-Menten equation to kinetic analysis of transport ATPases has been shown during continuous pH-metric recording of their activity. Two values of Km for both Na, K-ATPase and Ca-ATPase have been found to be consistent with the reported data. Both values of Km for Na, K-ATPase change with temperature, i. e. at 37 degrees, 26 degrees and 15 degrees C they are as follows: Km1--21, Km2--171; Km1--3.32, Km2--47; and Km1- 1,2, Km2--20 microM, respectively. This method of determination of Km and V for transport ATPases compares favourably with the previously used methods in resulting efficiency. PMID- 6250661 TI - [Syrian hamster sensitivity to tumor cell inoculation in the period of pregnancy and nursing the cubs]. AB - The influence of pregnancy and lactation on the sensitivity of females to the transplantation of tumor cells was studied in experiments with Syrian hamsters. During the first days of the joint keeping of males and females (1--6 days before pregnancy) the latter ones were shown to be more resistant to the transplantation of tumor cells as compared with unbearing females. However, days 1--8 of pregnancy and during lactation no subtantial differences were revealed between animal groups compared in the sensitivity to the transplantation of tumor cells. PMID- 6250660 TI - [Changes in the sodium current under the action of etmozin and lidocaine inside and outside the membrane of single rat myocardial cells]. AB - The voltage clamp experiments were carried out on single internally perfused rat myocardial cells. The effect of ethmozine (8 x 10(-5) g/ml) and lidocain (8 x 10( 6) g/ml) on the fast maximum inward sodium current (INa) was studied. The drugs were tested inside and outside the cell. INa was inhibited insignificantly when ethmozine was added inside the cell. After 5 min of ethmozine action outside the cell INa dropped on the average to 43 +/- 6% of its initial value. Under these conditions the reactivation constrant of INa did not change significantly. Lidocain depressed INa both when added outside and inside the cell. However, when lidocain was added outside the cell a longer period was needed to depress INa. Comparison of lidocain and ethmozine action outside and inside the myocardial cell has shown that the sites of action of these antiarrhythmic drugs on the cellular membrane are different. PMID- 6250662 TI - [Atypical incompatibility of the F-like factors of pA22-4, pAP39 and pA41 genetic transfer with the F-group incompatibility plasmids]. AB - A study was made of compatibility of three F-like factors of the genetic transfer (pAP22-4, pAP39, pAP41) identified in the cells of serologically typed E. coli strains with F-group incompatibility reference plasmids. The factors of pAP22-4 and pAP41 transfer are partly incompatible with groups FII, FIII, FIV, and FI, FIV, respectively, while the factors of pAP39 transfer are completely incompatible both with groups FI and FIV plasmids. PMID- 6250663 TI - [Measurement of ventilation-perfusion distribution by the inert gas method (author's transl)]. PMID- 6250664 TI - Guar crispbread in the diabetic diet. PMID- 6250665 TI - Cell mediated and humoral immune response in chickens infected with avian infectious bronchitis. PMID- 6250666 TI - The preservation of nerve cells in rat neostriatal slices maintained in vitro: a morphological study. AB - The in vitro preservation of neurons in 300 micron thin neostriatal slices, which are routinely used for electrophysiological studies, was examined by light and electron microscopy and was compared to 700 micron thick neostriatal slices. The thin slices displayed well-preserved cells after up to 5 h of incubation. This finding correlated well with whether electrical activity could be recorded. In cross-section, the thin slices consisted of three layers: the inner layer contained many intact cells (80%) and was sandwiched between the outer layers where deteriorating cells predominated. In contrast to the thin slices, the thick slices (700 micron) displayed no layering of intact cells in cross-section. Instead, the majority of cells throughout these thick slices was swollen (98%), with only small patches of intact cells. Two types of deteriorating cells were apparent: swollen cells and dark (pycnotic) cells. The proportion of swollen cells increased with incubation time. In the thin slices this swelling occurred in the outer layers with the middle layer of intact cells remaining relatively unchanged over long incubation periods, whereas all cells in the thick slices were swollen after 2 h of incubation. Dark cells were localized to the outer portion of both slices and the number of such dark cells did not change with incubation time. PMID- 6250667 TI - Hippocampal inhibition of pituitary-adrenocortical function in female rats. AB - To assess the influence of the hippocampus on ACTH secretion, plasma ACTH concentrations were compared in hippocampectomized and control rats under conditions of differing plasma corticosterone concentrations. In the PM, hippocampectomized rats had higher basal and 2-min ether-stress-induced ACTH concentrations than did cortex-removed controls. Basal PM plasma corticosterone concentrations were also significantly elevated in the hippocampectomized group. In the AM, there were no between-group differences. Adrenalectomy abolished the PM differences between cortical-control and hippocampectomized rats. PM hypersecretion of ACTH in the absence of the hippocampus suggests that this structure contributes an inhibitory component to the neural mechanisms regulating ACTH release. The fact that this increase in hormone concentrations is limited to the PM indicates that there is a circadian variation in hippocampal action. PMID- 6250668 TI - Inhibitory action of ibotenic acid on the crayfish neuromuscular junction. AB - The effect of ibotenic acid on the crayfish neuromuscular junction was investigated. Ibotenate reduced dose-dependently the amplitude of the excitatory junctional potentials (EJPs) elicited by repetitive stimulation of the excitatory axons. Ibotenate did not affect facilitation of successive EJPs. The decrease in the EJP amplitude caused by ibotenate was almost completely blocked by picrotoxin. A quantum analysis of extracellularly recorded EJPs demonstrated that the mean quantum content was reduced by ibotenate without remarkable change in unit size. Ibotenate increased the conductance change induced by ibotenate was observed even if the glutamate receptor was completely desensitized by the prolonged application of glutamate. From an analysis of the dose-response curve of GABA with or without ibotenate, it is suggested that ibotenate acts on the GABA receptor in the crayfish neuromuscular junction. PMID- 6250669 TI - Opiate and muscarinic ligand binding in five limbic areas after bilateral olfactory bulbectomy. AB - Bilateral olfactory bulbectomy (BBX) in mice leads to a variety of neutrochemical changes in 5 limbic areas associated with the bulbs. Within one week after BBX, opiate ligand binding declined by 73% in the amygdala, rose by 82% in the hypothalamus and then returned to sham levels by 4 weeks in both areas. Opiate binding also declined by 47% in the olfactory tubercle and to essentially zero in the piriform cortex and the olfactory peduncle after 16 weeks. Muscarinic cholinergic binding declined in the amygdala and hypothalamus at 16 weeks after BBX, but reductions in muscarinic binding were observed in the piriform cortex and the olfactory peduncle by two weeks postsurgery. Muscarinic binding in the olfactory tubercle was unaffected by BBX, as was binding of beta-adrenergic and benzodiazepine ligands in the limbic areas. Binding of [3H]spiroperidol rose 61% in the olfactory tubercle two weeks after surgery and then declined to normal levels. Choline acetyltransferase activity rose by 64% within one week after BBX in the piriform cortex and remained elevated throughout the study. Activity of this enzyme also rose in the olfactory peduncle and the olfactory tubercle after surgery. BBX had only moderate effects on glutamic acid decarboxylase in the limbic areas, and enzyme activity increased 25% in the olfactory tubercle and the piriform cortex 4 weeks after BBX. BBX also resulted in a moderate decrease (22%) in DOPA decarboxylase activity in the olfactory tubercle two weeks after BBX. The implications of these neurochemical changes are discussed in terms of what is known about bulb-limbic system connections. PMID- 6250670 TI - Naloxone antagonism of GABA-evoked membrane polarizations in cultured mouse spinal cord neurons. AB - Pharmacological studies using an in vitro model system were carried out to determine if naloxone, an opiate receptor antagonist, could have effects on neuronal membranes which were unrelated to its action as an opiate receptor antagonist. Intracellular recordings were made from cultured mammalian spinal cord neurons. Putative amino acid neurotransmitters and naloxone were applied by iontophoresis or superfusion. When naloxone was co-iontophoresed with the amino acids a depression of the GABA response resulted. This depression was dose dependent and reversible. At the lower doses of naloxone tested, the depression was specific since the glycine and glutamate responses were unaffected. At the higher doses of naloxone tested, alterations in the glycine and/or glutamate responses and membrane input resistance were frequently observed. The naloxone depression of the GABA response did not appear to involve opiate receptors since (+)-naloxone, the inactive isomer, equally depressed the GABA response. Analysis of the effect of naloxone on GABA dose-response curves indicates that naloxone acts as a competitive antagonist at the neuronal GABA receptors. Similar results were obtained when naloxone was applied by superfusion. However, high concentrations of naloxone (0.1-1 mM) were required, suggesting that naloxone has a low affinity for the GABA receptor. These data indicate that under some experimental conditions naloxone could not be considered a specific opiate antagonist. PMID- 6250672 TI - Receptive fields of neurons in areas 3b and 1 of somatosensory cortex in monkeys. AB - Receptive fields of neurons within the separate representations of the glabrous hand in areas 3b and 1 of somatosensory cortex were studied in cynomolgus monkeys. Many neurons in area 1 have center-surround receptive fields with separate 'on' and 'off' zones, while neurons in area 3b exhibit largely uniform or homogeneous receptive fields. PMID- 6250671 TI - Effects of thyroid state on brain development: beta-adrenergic receptors and 5' nucleotidase activity. AB - The effect of thyroid status on beta-adrenergic receptor binding and 5' nucleotidase activity was studied in the forebrain and the cerebellum of the rat during the first 5 postnatal weeks. The developmental increase in beta-adrenergic receptor binding was significantly depressed in thyroid deficiency in both the forebrain and the cerebellum. The effect was more pronounced in the cerebellum, where at day 35 the concentration and the total number of beta-adrenergic receptor sites were reduced by 35% and 50% respectively. In contrast, hyperthyroidism had no significant effect on the development of beta-adrenergic receptors in the brain. On the other hand, hyperthyroidism led to a sustained increase in the forebrain in the activity of 5'-nucleotidase, an enzyme which is also associated with plasma membranes and has been proposed to play some role in neurotransmission. In thyroid deficiency the enzyme activity was markedly depressed. The effect was significant from day 12 in the cerebellum and from day 21 in the forebrain, the maximal depression, at day 21, being 55% and 45% respectively. In comparison with these plasma membrane markers, the accretion of membranous proteins was less affected: although this was retarded in hypothyroidism and advanced in hyperthyroidism there was no residual effect at 35 days except those attributable to changes in organ size. The results indicated, therefore, that the biochemical specialization of cells, as reflected in certain plasma membrane constituents, are chatacteristically influenced in the developing brain by thyroid disorders. PMID- 6250673 TI - Identification of a second category of alpha-melanocyte-stimulating hormone (alpha-MSH) neurons in the rat hypothalamus. AB - An immunocytochemical localization of alpha-melanocyte-stimulating hormone (alpha MSH) as well as ACTH and a fragment (16K) of the common precursor of ACTH and beta-lipotropin (beta-LPH) was performed in rat brain. Two different groups of neuronal cell bodies showing alpha-MSH-like immunoreactivity (alpha-MSH-LI) were observed in the hypothalamus. One group of neurons located in the arcuate nucleus was shown to contain not only alpha-MSH-LI, but also ACTH and the 16K fragment. A second category of alpha-MSH-LI-containing neurons was characterized by the complete absence of staining for ACTH and 16K fragment. These neurons were mainly located in the dorsal-lateral portion of the hypothalamus. Immunoelectron microscopy showed that immunostaining for alpha-MSH was restricted to dense core vesicles in the positive perikarya. Nerve fibers staining for alpha-MSH (but not for ACTH and 16K fragment) were also observed outside the ACTH-beta-LPH pathway, especially in the cortex, caudate-putamen nucleus and hippocampus. These findings strongly suggest the presence of two different neuronal systems reacting with antibodies to alpha-MSH. PMID- 6250674 TI - Identification of neurons contributing to presynaptic inhibition in Aplysia californica. AB - Electrical stimulation of the connectives presynaptically inhibits the PSP from cell L10 to the left upper quadrant cells (LUQC). The present report describes the properties of some of the individual neurons contributing to this response. Action potentials produced in a cluster of cells in the abdominal ganglion reduce the amplitude of the L10-LUQC PSP for periods greater than 30 sec. At least some of their inhibitory action is mediated by a slow hyperpolarization of L10 which results in a decreased transmitter release. In other cases, however, the inhibition is produced with no significant alteration of L10 membrane potential, indicating that additional mechanisms may also be present. The neurons producing these effects are approximately 75 microns in diameter and are located on the left ventral surface of the ganglion. They have axons in the connectives and are thus activated by stimuli previously utilized to produce presynaptic inhibition. They appear to be some of the same cells that produce a slow inhibition of ink motoneuron L14; one of these has been identified as L32. The identification of these cells allows for the further biochemical, biophysical and morphological analysis of the events underlying presynaptic inhibition. PMID- 6250675 TI - Influence of unilateral olfactory bulbectomy on opiate and other binding sites in the contralateral bulb. AB - The neurochemical consequences of unilateral olfactory bulbectomy (UBX) in mice were determined in the remaining olfactory bulb at various times after surgery. The most significant finding was a progressive decline in opiate ligand (dihydromorphine) and naloxone) binding that appeared within 11 days after surgery and persisted throughout the study. Statistically significant declines in spiroperidol (-67%), clonidine (-48%) and muscimol (-16%) binding were also observed 90 days after surgery. At 180 days postsurgery we observed a 20% increase in diazepam binding. No effect of UBX on dihydroalprenolol, quinucludinylbenzilate or serotonin ligand binding was observed. Bulbectomy resulted in a moderate decrease (-28%) in DOPA decarboxylase activity 14 days after surgery, which returned to normal by 30 days. Glutamic acid decarboxylase activity decreased by 37% 7 days after UBX, returned to normal by 14 days after surgery and then increased by 25% 90 days after UBX. Unilateral bulbectomy had no effect on cholineacetyltransferase activity in the remaining bulb. Thus, following a unilateral procedure, one bulb cannot necessarily serve as a valid control for the other. Possible explanations for the neurochemical changes observed are discussed. PMID- 6250676 TI - Opiate antagonist receptor binding in vivo: evidence for a new receptor binding model. AB - The in vivo accumulation and retention of the opiate antagonist tracers [3H]diprenorphine and [3H]naloxone at cerebral opiate receptor sites in rats exceed that expected from their known in vitro receptor affinities. The [3H]diprenorphine serum and brain levels can be stimulated with a pharmacokinetic model that contains the receptors in a micro-compartment. The receptor micro compartment consists of a population of binding sites next to a diffusion boundary which restricts ligand diffusion away from the receptor. Such an arrangement introduces a delay in the binding equilibrium of potent antagonists with the receptor sites and an increase in the apparent in vivo receptor affinity at subsaturating doses of the ligand; at saturating ligand concentrations these functions of the receptor micro-compartment are abolished. A physiological interpretation of the receptor micro-compartment could be the location of clustered opiate receptor sites on the exterior cell surface next to the synaptic cleft as the diffusion boundary. This kinetic approach involving a combination of pharmacokinetics and drug-receptor interactions permits the quantitative analysis of receptor site availability in the intact animal. Our results support the hypothesis that only one receptor population affects the in vivo disposition of the antagonist tracers, while they do not exclude the presence of low affinity binding sites that have been observed with the use of [3H]naloxone in vitro. Moreover, the binding site population observed in vivo may be responsible for mediating opiate agonist analgesia. PMID- 6250677 TI - Nerve growth factor receptors: analysis of the interaction of beta NGF with membranes of chick embryo dorsal root ganglia. AB - The binding of the beta subunit of Nerve Growth Factor (beta NGF) to membrane preparations of 8-day chick embryo dorsal root ganglia (DRG) has been investigated under conditions similar to those used to study the binding of beta NGF to intact single cell dissociates of DRG. The equilibrium binding data reveal heterogeneityy of binding that is more complex than that seen with intact cells. Binding is not saturable up to 125I beta NGF concentrations of 10(-8) M. Steady state and kinetic binding data show two sites with dissociation constants similar to those found on DRG cells. In addition, displacement data reveal a binding component with lower affinity (Kd = 10(-6) M) which is not found on intact cells. As with intact cells, the difference in the affinities of the two high affinity sites has been shown to be due to different rate constants of dissociation. The kinetics of dissociation of NGF are slower with membranes than with cells, and dissociation characteristics of 125I beta NGF change with increasing time of exposure to membranes. Degradation of 125I beta NGF during incubation with membranes is minimal and does not complicate the analysis of steady-state binding. Insulin does not bind to either of the two high affinity sites. Heterogeneity of the 125I beta NGF preparation and cooperativity of binding as a cause for the heterogeneity of the binding of NGF has been ruled out. Although there was an apparent increase in the rate of dissociation of 125I beta NGF in the presence of unlabelled NGF, a finding previously interpreted as evidence for negative cooperativity, this was shown to be independent of receptor site occupancy by NGF, and in part due to isotopic dilution within a diffusion barrier around the membranes. PMID- 6250678 TI - Thermoregulatory effects of (D-ala2)-methionine-enkephalinamide in the cat. Evidence for multiple naloxone-sensitive opioid receptors. AB - (D-ala2)-methionine-enkephalinamide (DAME) was injected into the third cerebral ventricle of unrestrained cats. At ambient temperature (Ta) = 22 degrees C, 3.1 50 micrograms caused dose-related hyperthermias. As dosage was increased, the hyperthermias diminished and in some cats hypothermia developed. Hyperthermia was not due to pyrogenic contamination or prostaglandin synthesis since it was not altered by pretreatment with a large IV dose of indomethacin. However, pretreatment with naloxone did cause a dose-related reduction in the hyperthermia. A low dose of DAME (12.5 micrograms) also caused hyperthermia at Ta = 4 and 32 degrees C, indicative of an increase in the level about which body temperature was regulated. On the other hand, a dose of 200 micrograms, which caused hyperthermia Ta = 22 and 32 degrees C, usually caused hypothermia at Ta = 4 degrees C, perhaps due to impairment of thermoregulatory control mechanisms. The response to DAME in the cold was reduced by naloxone pretreatment or reversed by subsequent injection of naloxone. Differences in hyperthermic patterns over a range of TaS and the lack of hypothermogenic action of morphine indicate that DAME alters thermoregulation in the cat by acting on morphine-insensitive, but naloxone-sensitive receptors. Central injection of beta-endorphin (5-50 micrograms) caused a dose-related hyperthermia. (Des-tyr1)-leucine-enkephalin (10 250 micrograms) was weakly hyperthermogenic, and kyotorphin (500 micrograms) did not consistently alter body temperature. PMID- 6250679 TI - The effect of an injection of corticotrophin on plasma concentrations of corticosterone, growth hormone and prolactin in two strains of domestic fowl. AB - 1. Three-week-old Light Sussex (LS) and Rhode Island Red (RIR) chicks were injected with long-acting corticotrophin (ACTH: 30 IU/kg) and the plasma concentrations of corticosterone, growth hormone (GH) and prolactin were determined over a 6-h period. Plasma concentrations of corticosterone and growth hormone were also measured after an injection of corticosterone (500 microgram/kg). 2. The resting plasma concentration of corticosterone in LS was less than that in RIR birds. The increase elicited by ACTH was smaller in LS but, since it was maintained for longer, the plasma corticosterone response was at least 18% larger than that in RIR birds. 3. Plasma GH concentration was decreased after an injection of ACTH in both strains but the decrease lasted longer in the LS chicks. 4. Plasma prolactin concentration was unaffected by ACTH. 5. After intra-abdominal injection of corticosterone, plasma GH concentration was depressed in both strains. It is concluded that ACTH-induced depression of plasma GH and growth is mediated by corticosterone. PMID- 6250680 TI - Carotid body tumors: a 40-year study. AB - A total of 44 carotid body tumors were observed for over 40 years at Memorial Sloan-Kettering Cancer Center in New York. The true nature of th paraganglioma can remain obscure in those patients without prior tissue biopsy or sophisticated diagnostic studies. Eighteen patients came to surgery without a primary working diagnosis of the conditions, 43 percent of the seris. Significant advances in the preoperative workup of a cervical mass attached to the carotid sheath are now recommended: ultrasonography, radioisotope perfusion scanning, and selective carotid arteriography. Catecholamine determination should be considered for any paraganglioma exhibiting vasomotor instability or hypertension. Prior to 1945 the carotid bifurcation was sacrificed eight times with a 50 percent mortality occurring in relatively youthful subjects. In the 35 years since then, a more sophisticated surgical technique preserving the carotid circulation has resulted in over 30 resections with but one fatality. Multicentricity, both in the sporadic and the familial form, is characteristic of this rare tumor, also called "APUDoma." (APUD is an acronym derived from three of the most important characteristics of these cells: a high amine content, amine precursor uptake, and decarboxylation. Its malignant potential is beyond debate. PMID- 6250681 TI - Is THC an effective antiemetic for cancer patients? Opinion 1. PMID- 6250682 TI - Is THC an effective antiemetic for cancer patients? Opinion 2. PMID- 6250683 TI - Reticulocyte membrane transferrin receptors. AB - A membrane protein with specific transferrin binding activity has been isolated from rabbit reticulocytes. The isolation procedure involved the immunoprecipitation by antibody to transferrin of transferrin-receptor complexes from reticulocyte membrane proteins which had been solubilized with nonionic detergent. Receptor dissociated from the antibody-transferrin-receptor complexes could bind transferrin saturably and reversibly. It migrated electrophoretically as a single band of glycoprotein with an estimated molecular weight of approximately 180 000 which was reduced to around 93 000 following complete dissociation with dithiothreitol. PMID- 6250684 TI - Studies on the pathogenesis of pseudorabies in domestic cats following oral inoculation. AB - Domestic cats were inoculated orally with an Iowa isolate of pseudorabies virus. Several cats were killed at intervals of one day and tissues were examined virologically and histologically to determine the initial sites of virus penetration and replication and to evaluate the pathways traveled by the virus from the mouth to the central nervous system. Lesions were consistent in the tonsils, along the pathways of the sensory branches of the ninth and tenth cranial nerves, the tractus and nucleus solitarius and the area postrema in the medulla. Less consistent lesions in the ganglia and nuclei of the fifth cranial nerve indicated a lesser role for the passage of virus via this nerve. Nervous lesions consisted of multifocal to diffuse microgliosis, mononuclear perivascular cuffing and a mononuclear inflammatory cell infiltration with a variable number of neutrophils occasionally forming microabscesses. Virus isolations correlated well with microscopic lesions. Ultrastructurally, virions were observed within the nucleus of the neurons in the medulla. Clinical signs were similar to those previously reported. Pruritus was consistently absent. Virus was isolated consistently for the first two or three days postinoculation from oral and nasal secretions but not from secretions after three days. PMID- 6250685 TI - Proteolytic enzymes and rotavirus SA-11 plaque formation. AB - In addition to trypsin, eight other proteolytic enzyme preparations were tested for their ability to assist simian rotavirus SA-11 plaque formation in MA-104 cells. When incorporated in the overlay (minimal essential medium and 0.7% Ionagar No. 2) in the concentrations per mL indicated, alpha-chymotrypsin (10 micrograms), elastase (0.5 micrograms), subtilisin (0.5 micrograms), pronase (2.5 micrograms) and pancreatin (25 micrograms) were as efficient as trypsin (5 micrograms) in helping SA-11 produce 3-4 mm diameter plaques after five days of incubation at 37 degrees C. No plaques were produced when pepsin (25 micrograms), papain (10 micrograms) or thermolysin (10 micrograms) was added to the overlay. Addition of soybean trypsin inhibitor to alpha-chymotrypsin-, pronase- or pancreatin-containing overlays completely inhibited virus plaque production. A similar effect was not seen with elastase or subtilisin. PMID- 6250686 TI - Effect of prostaglandin E1-induced elevation of cyclic AMP on glucose repression in the lactic streptococci. AB - Cyclic adenosine 3', 5' -monophosphate (cAMP) activity was observed in Streptococcus lactis C2, Streptococcus cremoris C10, Streptococcus diacetlactis 18-16, and Streptococcus thermophilus C3. In vitro assays of cell-free extracts obtaianed from S. lactis C2 showed that the cAMP-associated enzymes adenyl cyclase and phosphodiesterase were also present. In vitro experiments showed that prostaglandin E1 (PGE) stimulation of adenyl cyclase increased cAMP concentrations approximately fivefold, and in vivo studies showed that PGE treatment of S. lactis C2 increased intracellular cAMP concentrations twofold. Futhermore, PGE-induced elevation of intracellular cAMP levels was shown to prevent the repression of ss-D-phosphogalactoside galactohydrolase synthesis by glucose. PMID- 6250687 TI - Purification and characterization of exocellular proteases produced by a clinical isolate and a laboratory strain of Pseudomonas aeruginosa. AB - Exocellular protease production was examined in two separate strains of Pseudomonas aeruginosa, one a clinical isolate and the other a laboratory strain. Both strains produced two separate proteases (proteases 1 and 2) which were indistinguishable from one strain to the other. The two proteases were purified by a two-step procedure of gel filtration chromatography followed by ion-exchange chromatography. Proteases 1 and 2 were shown to be distinct serologically and unrelated by physiochemical parameters examined. Protease 1 was the major exocellular protein produced and contributed about 95% of the total protease activity of the culture. It was etimated to have a molecular weight of 34850 and was also shown to contain 10% glucosamine by weight. Protease 2, in contrast, had an estimated molecular weight of 52750 and contained no detectable carbohydrate. Proteases 1 and 2 were both stimulated by Ca2+, and Mg2+ and inhibited by Co2+Zn2+, and 1,10-o-phenanthroline. Protease 1 was also inhibited by EDTA. In addition to protease activity, both proteases 1 and 2 demonstrated elastase activity as well as a limited collagenase activity. Specificity of the two protease against synthetic peptides was, however, quite different. Protease 1, but not protease 2, showed a preference for peptide bonds in which the amino group was contributed by an amino acid with a hydrophovic R group. PMID- 6250689 TI - The effect of cortisol on glycogen and fructose-1,6-bisphosphatase in baby hamster kidney cells infected with Chlamydia trachomatis. AB - This study was designed to assay changes in glycogen synthesis which may occur as a result of cortisol treatment of chlamydial-infected cells. Monolayers of baby hamster kidney (BHK) cells, unlabeled and prelabeled with [6-14C]glucose, were treated with various concentrations of cortisol before (pretreated) or during (post-treated) infection with Chlamydia trachomatis. At designated times after absorption, the cells were harvested and assayed for total glycogen and 14C accumulation in glycogen. The total amount of glycogen accumulated in cells during the period of greatest chlamydial glycogen synthesis (36 h) was not affected by cortisol treatment. Cortisol treatment appeared to have retarded the accumulation of glycogen in treated infected cells until 30 h after infection. Treated infected cells prelabeled with [6-14C]glucose accumulated a greater amount of 14C in glycogen than untreated infected cells. All cortisol-treated, infected cells exhibited elevated levels of fructose-1,6-bisphosphatase activity, whereas untreated infected cells did not. The hypothesis that cortisol affects chlamydia multiplication by altering the intracellular environment of the host cell is compatible with the results obtained. PMID- 6250688 TI - Consequences of interaction between F plasmid and a drug-resistance plasmid belonging to incompatibility group F1. AB - Two plasmids, pLK1 and pLK2, were derived from pIP218, an in vivo recombinant of plasmid F and the drug-resistance plasmid pIP176 (Cmr, Smr, Sur, Tcr). Of these two plasmids, pLK1 is 70 Mdaltons and carries the Tc-resistance determinant in a 7-Mdalton transposition element; pLK2 is 125 Mdaltons and carries Cm-, Sm- and Su resistance determinants. The plasmid pLK1 resulted as a Tc-resistance segregaant of PIP218 during its coexistence with another plasmid, Co1E1-araC101, and pLK2 (125 Mdaltons) as a CmrSmrSur segregant during the conjugal transfer of pIP218. Both plasmids belong to the F1-incompatibility group, surface-exclude each other and Flac, and are derepressed for transfer. Incompatibility studies also indicated the preferential maintenance of pLK2 in hosts carrying either pLK2 and pLK1, or pLK2 and F'lac. An explanation of this phenomenon is provided. Furthermore, our data suggest the illegitimate recombination of the chromosomal lac genes with pLK1. In course of the incompatibility studies, the tet determinant was transposed from pLK1 into the chromosome, from the chromosome into the lac genes of an Flac plasmid, and from the Flac plasmid into another site on a second Flac plasmid. PMID- 6250690 TI - Lethal effect of polymyxin B sulfate in experimental Proteus rettgeri infection in mice. AB - The mouse model of intraperitoneal sepsis with Proteus rettgeri was used to evaluate the anti-endotoxic effect of polymyxin B sulfate. An unexpected reversal of the usual protective effect of polymyxin in experimental enterobacterial sepsis was observed in which the lethality of the infection was enhanced. PMID- 6250691 TI - Immunofluorescent detection of double-stranded RNA in cells infected with reovirus, infectious pancreatic necrosis virus, and infectious bursal disease virus. AB - Urea treatment of ethanol-fixed virus-infected cells exposed nucleic acid antigens for immunofluorescence. Three double-stranded (ds) RNA-containing viruses showed bright fluorescence using antibodies against dsRNA. Three single stranded RNA-containing viruses showed less intense fluorescence with anti-dsRNA. Four out of five cell lines persistently infected with various RNA-containing viruses showed no dsRNA detectable by immunofluorescence. PMID- 6250692 TI - Diagnosis of rotavirus, adenovirus, and herpesvirus infections by immune electron microscopy using a serum-in-agar diffusion method. AB - The sensitivity of immune electron microscopy (IEM) for the detection and identification of bovine rotavirus, infectious bovine rhinotracheitis virus (IBR), and canine adenovirus has been studied by using the serum-in-agar (SIA) method in which a specific antiserum has been incorporated in agar. PMID- 6250693 TI - Characterization of an Escherichia coli mutant which utilizes glycerol in the absence of cyclic adenosine monophosphate. AB - The aerobic catabolism of glycerol depends on the expression of the glpK operon specifying a glycerol kinase and the glpD operon specifying an sn-glycerol-3 phosphate (G3P) dehydrogenase. It has not been clearly established how the expression of these operons is dependent on adenosine 3',5'-cyclic monophosphate (cAMP). We have isolated a promoterlike mutant (CA8306B) which, owing to a mutation in the glpK operon, can utilize glycerol in the absence of cAMP. Glycerol kinase and G3P dehydrogenase are inducible in CA8306B and its wild-type parent CA8000. The induced level of glycerol kinase in CA8306B is 30% that of CA8000 and this level is increased fivefold by the addition of cAMP. However, the induced level of G3P dehydrogenase in CA8306B is similar to that of CA8000 and is unaffected by cAMP addition. These results suggest that the promotion of the glpK operon requires cAMP whereas the promotion of the glpD operon does not. PMID- 6250694 TI - Chlamydia psittaci: inclusion vacuole ultrastructure. AB - The inclusion ultrastructure of fibroblasts infected with Chlamydia psittaci (6BC) was studied. Electron microscopic techniques were used which permitted the observation of whole infected host cells and 1.0-micron sectioned preparations. It was shown that the cytoplasmic inclusion vacuoles of infected cells contained interconnecting structures within which chlamydiae reproduce. PMID- 6250695 TI - Cooperation between herpes simplex virus specific alpha protein and host cell RNA polymerase II in the transcription of viral deoxypyrimidine kinase. AB - A cistron specific enzyme-forming capacity method was used to study the control of herpes simplex virus (HSV) specific deoxypyrimidine kinase (dPyK) mRNA synthesis. In this assay, the alpha (or immediately early) protein was required to effect the transcription of dPyK mRNA. However, the dPyK mRNA synthesis was sensitive to alpha-amanitin in alpha-amanitin sensitive cells and resistant to alpha-amanitin in alpha-amanitin resistant cells. The effective dose range of alpha-amanitin used and the genetic lesion in alpha-amanitin resistant cells suggested that cellular DNA-dependent RNA polymerase II was also involved in the transcription of dPyK. This study suggests that two components, the HSV alpha protein and the cellular RNA polymerase, II, were required for dPyK mRNA synthesis. PMID- 6250696 TI - Immunohistochemical study of foci of recent cell death in Huntington's disease. AB - Foci of recent cell death were identified in 10 consecutive cases of Huntington's disease in the caudate nucleus and putamen. Indirect immunohistochemical staining procedures were performed on these areas and controls using fluorescein conjugated anti-globulin and peroxidase-conjugated anti-globulin. Positive results were found when human antiserum to Cytomegalovirus was used. The possibility of abnormal antigen presence within the dying neurons in this disease is discussed. PMID- 6250697 TI - Peripheral neuropathies associated with chronic renal failure. AB - A variety of peripheral nerve disorders may be associated with chronic renal failure. The polyneuropathy due to uremic toxins is a distal, motor and sensory polyneuropathy in which there is segmental demyelination, axonal degeneration, and segmental remyelination. The nature of the uremic toxin and the underly mechanism of these changes is unknown. The incidence in patients with "end-stage" renal disease has fallen in recent years, severe cases now being rare, perhaps due to refinements in chronic hemodialysis, transplantation, and other therapies. However, while chronic hemodialysis stabilizes uremic neuropathy, manipulation of hemodialysis schedules may not alter its course, according to current assessment. Successful renal transplantation improves both the clinical and electrophysiological signs, even in severe uremic neuropathy. PMID- 6250698 TI - Endorphins--morphine-like peptides of brain. PMID- 6250700 TI - [Plasma and urine steroids in essential hypertension with normal and suppressed renin and in primary hyperaldosteronism. Changes after ACTH stimulation]. PMID- 6250699 TI - Double-blind comparison of the antiemetic effects of nabilone and prochlorperazine on chemotherapy-induced emesis. AB - The antiemetic effect of oral nabilone, a synthetic cannabinoid, given at a dose of 2 mg every 12 hours was compared to oral slow-release capsules of prochlorperazine given at a dose of 10 mg every 12 hours by a double-blind crossover method in 37 patients receiving cancer chemotherapy. Patients received one of the following as the primary emetic stimulus: high-dose cis dichlorodiammineplatinum(II) (DDP), low-dose DDP, mechlorethamine, streptozotocin, actinomycin D, or DTIC. Although results varied according to strength of emetic stimulus received, both nabilone and prochlorperazine appeared to produce antiemetic effects. Eighteen of the 37 patients achieved a complete or partial elimination of symptoms: seven with nabilone alone, three with prochlorperazine alone, and eight with each drug. Nabilone appeared to be the more effective antiemetic for patients who received chemotherapy agents other than high dose DDP; it was equivalent to prochlorperazine for those who did receive high-dose DDP. Side effects from prochlorperazine were limited to mild drowsiness occurring among 35% of the patients. The side effects from nabilone were drowsiness and dizziness which occurred frequently and were dose-limiting in 25% of patients. PMID- 6250701 TI - Mechanism involved in the response of granulated vesicles in the mouse pinealocyte to acute cold exposure. AB - Quantitative electron microscopic studies on the mouse pineal gland were done to elucidate the mechanism of the response of the granulated vesicles in pinealocytes to acute cold exposure. An increase in the number of the granulated vesicles in the mouse pinealocytes occurs following administration of isoproterenol and this increase is prevented by pretreatment with the beta adrenergic blocking agent, propranolol. In addition, a numerical increase of the granulated vesicles in response to acute cold exposure is abolished in mice pretreated with propranolol or in adrenalectomized animals. The results suggest that catecholamines released from the adrenal medulla, but not from sympathetic nerve endings, may cause the response of the granulated vesicles to cold by way of beta-receptors. PMID- 6250702 TI - Long cytoplasmic processes in pancreatic polypeptide cells. AB - Pancreatic polypeptide (PP) cells were studied in human endocrine pancreatic tumours and in normal human pancreata by immunohistochemical techniques and electron miscroscopy. The existence of long cytoplasmic processes was demonstrated both in tumours and normal tissue. These processes are in close contact with other endocrine cells or with acinar cells. This particular morphological aspect suggests that PP cells may control the function of other cells via paracrine secretion. PMID- 6250703 TI - Hormone-induced filopodium formation and movement of pigment, carotenoid droplets, into newly formed filopodia. AB - Treatment of cultured goldfish xanthophores by hormone (ACTH) or c-AMP induces not only pigment dispersion, but subsequent outgrowth of processes, and pigment translocation into these processes. These latter effects are shown to proceed as follows: First the edge of the cytoplasmic lamellae takes on a scalloped contour with numerous protrusions. These presumably serve as nucleation centers where short microfilament bundles are assembled. Later, the microfilament bundles elongate ("grow"), often resulting in an extension of the protrusions to become filopodia while the proximal end of the microfilaments penetrates into the thicker portion of the cellular process which now houses the pigment, i.e., the carotenoid droplets. Carotenoid droplets appear to migrate along the microfilament bundles, or cytoplasmic channels associated with them, into the filopodia. Finally, some of the filopodia become broader, thicker and laden with carotenoid droplets and are then recognized by light microscopy as pigmented cellular processes. The microfilaments have been shown to be actin filaments by their thickness, the size of their subunits, and decoration by heavy meromyosin. Evidence is presented which suggests that the growth of these actin filaments may come about by recruitment from short F-actin strands found in random orientation in adjacent areas. PMID- 6250704 TI - Ultrastructural investigation of ACTH immunoreactivity in arcuate and supraoptic nuclei of the rat. AB - Fine structural localization of an ACTH-like substance was obtained in neurons of the rat arcuate nucleus using immuno-electron microscopy, whereas it could not be confirmed that ACTH-containing cell bodies are present in the supraoptic nucleus. The immunoreactive cells of the arcuate nucleus appeared to be more numerous than the unreactive neurons. Immunostaining was carried out before embedding in resin. Empty vesicles of irregular shape were found in dendrites of immunoreactive arcuate neurons, but their significance and nature remain enigmatic. The reaction product was distributed uniformly throughout the cytoplasm of the ACTH-positive cells, except that the mitochondria, rough endoplasmic reticulum and Golgi vesicles and cisternae were devoid of PAP molecules. This distribution differed from the localization reported in ACTH-secreting cells of the rat anterior pituitary, where the reaction product was found in the rough endoplasmic reticulum and Golgi complex as well as in secretory granules. PMID- 6250706 TI - Terminal stages of SV40 DNA replication proceed via multiply intertwined catenated dimers. AB - We have identified a new class of SV40 replicative intermediates which consists of a least 20 discrete DNA species. All members of this class are catenated dimers, two circular molecules of SV40 duplex DNA linked topologically by one or more intertwining events. Most of these molecules are linked by several intertwining events, and the range of linkage states observed runs from L = 1 to L = 10. A catenated dimer with a given linkage state is assigned to one of three distinct families (A, B or C) depending on the open or covalently closed nature of its two circular components: in form A catenated dimers, both circles are nicked or gapped; in form B, one of the circles is supercoiled; and in form C, both circles are supercoiled. Members of all three of these families are found in SV40 chromatin pulse-labeled with 3H-thymidine, and together they comprise 10-20% of the total replicative form SV40 DNA, appearing as a discrete series of electrophoretically resolved bands superimposed upon a continuous smear of growing cairns structures. The distribution of linkage states varies between the families, A being the most intertwined and C the least intertwined. Upon a chase with cold thymidine, label is lost rapidly from all these catenated DNA species. We suggest that the sequence A leads to B leads to C leads to mature monomeric supercoiled SV40 DNA represents the final stages of SV40 replication, and that a special enzyme activity exists in vivo to uncatenate the SV40 daughter chromosomes. PMID- 6250705 TI - Immunohistochemical study of the pars tuberalis of the adenohypophysis in the monkey, Macaca irus. AB - The pars tuberalis of the hypophysis in the monkey Macaca irus encompasses the hypophysial stem up to the median eminence. Histologically, it consists of several layers of chromophobic cells. A few PAS-positive cells also stainable with Alcian blue (pH 3.0) can be observed among the unstained elements. Using the indirect immunofluorescence antibody technique, scattered immunoreactive cells were revealed with the anti-beta oLH antibody; these cells did not react with the anti-beta hFSH antibody. In contrast, the immunoreactions to anti-hGH, anti-hPRL, anti-ACTH, anti-MSH, anti-LPH and anti-endorphin sera were completely negative. Single cells reacting with the anti-beta hTSH serum were observed at the inferior end of the hypophysial stalk (zona tuberalis), i.e., beyond the pars tuberalis proper. These results are compared with data reported in the literature. PMID- 6250707 TI - ATP-dependent DNA topoisonmerase from D. melanogaster reversibly catenates duplex DNA rings. AB - Extracts of Drosophila embryos contain an enzymatic activity that converts circular DNAs into huge networks of catenated rings in an ATP-dependent fashion. The catenated activity is resolved into two protein components during purification. One component is a novel DNA topoisomerase that requires the presence of ATP in order to relax supercoiled DNA. We have shown that the ATP dependent DNA topoisomerase relaxes DNA by a mechanism distinct from that of nicking-closing enzymes. The Drosophila ATP-dependent topoisomerase allows one segment of a circular DNA to pass through transient breaks in both strands at another site on the DNA circle without any relative rotation between the ends at the transient break. This mechanism can convert negative supertwists to positive twists and vice versa until a relaxed equilibrium state is reached. The formation of catenated rings is mediated by an analogous bimolecular reaction which can occur between two nonhomologous DNA circles. The catenation reaction is fully reversible: in the presence of the second protein component, circular DNA is converted quantitatively into catenated forms; in its absence, the ATP-dependent topoisomerase resolves catenated networks back into monomer circles. The Drosophila ATP-dependent topoisomerase appears to be closely related to E. coli DNA gyrase in that both use a similar mechanism to change the topology of DNA, both require ATP and both are inhibited by the antibiotic novobiocin. The presence of an enzyme that allows one DNA helix to pass freely through another could not only be useful in relaxation of topological constraints, but also may be involved in the folding and unfolding of eucaryotic chromosomes. PMID- 6250708 TI - Characteristics of an SV40-plasmid recombinant and its movement into and out of the genome of a murine cell. AB - A bacterial plasmid carrying the early region of SV40 (pOT) has been stably established in high molecular weight (hmw) DNA of mouse L cells by selection for the herpes virus thymidine kinase (tk) gene. DNA blotting has demonstrated that most cell lines contain multiple discrete copies of pOT, generally with an intact SV40 early region. No free copies of pOT have been detected. Both pOT and tk sequences may be amplified up to 20-200 copies of the SV40 early region. In contrast to the uniform staining pattern normally observed in SV40-transformed lines, indirect immunofluorescence using antiserum to the SV40 T antigen has demonstrated that the expression of the early region is heterogeneous in these cell lines. This fraction expressing T is characteristic of a given cell line, and varies from 0 to 99% positive. Several pOT cell lines have been fused to simian cells, and replicating low molecular weight DNAs were isolated from the heterokaryons. Transformation of E. coli with this DNA demonstrates that pOT can be rescued from hmw DNA in L cells and reestablished as a plasmid in E. coli. Excision is generally precise when pOT is introduced to the murine cells as supercoiled molecule, and imprecise when pOT is introduced in linear form. PMID- 6250709 TI - Defined oligomeric SV40 DNA: a sensitive probe of general recombination in somatic cells. AB - We have constructed well defined oligomeric molecules of simian virus 40 (SV40) DNA as probes for investigating mechanisms by which cultured somatic cells recombine DNA. Restriction enzyme fragments from different temperature-sensitive mutants were joined in a head-to-tail orientation to create partial dimers 1.84 genome lengths in size. These molecules are too large to fit into a viral capsid. Therefore an assay that depends on production of progeny virus after infection with oligomeric DNA is a selective measure of precise conversion of oligomers to monomers. By constructing oligomers from appropriate combinations of temperature sensitive DNAs, we have been able to study the conversion process in several defined regions of the SV40 genome. Our results indicate that conversion of oligomers to monomers occurs uniformly throughout the genome and is not dependent on normal viral DNA replication. These data indicate that conversion occurs primarily by general, homology-dependent recombination. At least one secondary mechanism that generates a low level of wild-type progeny was also detected. Studies with heteroduplex molecules indicate that repair of mismatched bases may be the secondary mechanism. PMID- 6250710 TI - DNA sequence organization of the beta-globin complex in the BALB/c mouse. AB - Clones containing five non-adult beta-globin genes were isolated from a library of BALB/c DNA. Together, the newly cloned regions comprise a contiguous block of 32 kb of the mouse genome. Restriction mapping of genomic DNA established the physical linkage of these non-adult genes to the two adult beta-globin genes as well as the two adult genes to each other. Thus this entire BALB/c beta-globin complex consists of seven linked genes, all with the same transcriptional orientation, arrayed over 70 kb of DNA. The order of these genes is: 5'-epsilon y3-beta h0-beta h1-beta h2-beta h3-beta major-beta minor-3' Portions of each of the five newly identified genes have been sequenced. Only one, epsilon y3, encodes a previously described globin. beta h0 and beta h1, which are closely related, differ significantly from both adult and embryonic globins. The beta h2 sequence is more closely related to the adult genes than to the other non-adult genes. However, it is the sequence least homologous to both of these classes. The 5' half of the beta h3 gene (preceding codon 75) has an aberrant structure. The rest of this sequence is intact, resembling an adult beta-globin gene except for an inserted base at cocon 90, resulting in a frameshift. Consequently, the beta h3 sequence cannot be translated to produce a normal beta-globin. PMID- 6250711 TI - Evolution of a D. melanogaster glutamate tRNA gene cluster. AB - We have determined the DNA sequence of a cloned cluster of essentially identical glutamate tRNA genes of D. melanogaster. The cluster consists of five genes: a gene triplet spanning approximately 0.55 kb followed by a 0.45 kb gene doublet 3.0 kb downstream. The genes are all arranged with the same polarity, do not encode the tRNA CCA end and contain no intervening sequences. Examination of the 5' and 3' sequences immediately flanking each gene reveals a striking pattern of sequence homologies between certain of the genes, which suggests a possible evolutionary history of this gene cluster. We propose that two ancestral genes each gave rise to gene doublets by duplication, while one of these gene pairs then gave rise, in turn, to a trio of genes as a result of unequal crossover. PMID- 6250712 TI - Genetic events associated with an insertion mutation in yeast. AB - The his4-912 mutation shares similar genetic properties with mutations promoted by procaryotic insertion elements. This mutation lacks all three his4 functions. Many different classes of His+ revertants have been obtained from his4-912. The most frequent class of His+ revertants results from a site mutation which confers a cold-sensitive His- phenotype. Other classes of revertants contain translocations (one between chromosomes I and III and the other between chromosomes III and XII), a transposition of the his4 region to chromosome VIII, and an inversion of most of the left arm of chromosome III. Another class contains deletions which extend from his4-912 into the his4 region. In each of these classes of revertants, the his4 region is closely linked to the chromosomal aberration. Many of these revertants contain additional changes in chromosome structure (duplication, deletion and aneuploidy) that are unrelated to the reversion of his4-912 to His4+. PMID- 6250713 TI - DNA rearrangements associated with a transposable element in yeast. AB - The his4-912 mutation results from insertion of a 6200 bp transposable element into the his4 gene of yeast. In order to clone the his4-912 mutation, the plasmid pBR322 was integrated into the his4 gene by means of yeast transformation, and then the vector sequences and the his4-912 insertion element were excised as a single restriction fragment. This his 4-912 insertion element is homologous to Ty1, a family of repetitive yeast DNA sequences. His+ revertants derived from the his4-912 mutant carry a number of chromosomal aberrations including deletions, translocations, a transposition and an inversion. The majority of His+ revertants result from deletions which have both endpoints within the element and which leave behind only 300 bp of the insertion element. Other derivatives of the his4 912 mutant carry deletions which have one endpoint in the insertion element and one endpoint in the his4 coding sequence. In two His+ revertants carrying reciprocal translocations, the chromosome III translocation breakpoints occur within the his4-912 insertion element. A His+ revertant carrying an inversion of most of the left arm of chromosome III may be an intermediate in transposition of the his4-912 insertion element to a new site on chromosome III. PMID- 6250714 TI - The transposition properties of Tn2 in E. coli. AB - We report the characterization of Tn2 transpositions into the chromosome and into an F' lacproB episome of E. coli. When Tn2 transposes into the chromosome a proportion of the insertions result in auxotrophy. These insertions can revert to prototrophs and lose ampicillin resistance concomitantly. However, Tn2 insertions in F' lacproB are often associated with deletions, and it seems probable that insertion and deletion occur simultaneously. PMID- 6250715 TI - Unique mode of transcription in vitro by Vesicular stomatitis virus. AB - In addition to the five mRNA species and 47 nucleotide long leader RNA synthesized by purified virions of vesicular stomatitis virus, at least three discrete low molecular weight RNA species having approximate chain lengths of 28, 42 and 70 nucleotides can be detected in vitro. Each of these RNA species displays a unique and characteristic T1 fingerprint profile and contains (p)ppAA as its 5' terminus. By partial sequence analyses, two of the small RNA products, 42 and 28 bases long, were found to contain 5' terminal sequences identical to those in the N and NS mRNAs, respectively. Ultraviolet inactivation studies demonstrate that each of these RNA species has a target size in agreement with its molecular weight indicating independent initiation. Kinetic studies show that the small RNA species are synthesized within 1 min, while mRNA chain completion occurs later in the sequential order N-NS-M-G. These results indicate that viral mRNA synthesis occurs in vitro by multiple initiations at different promoter sites on the genome RNA, and that the elongation and completion of the individual mRNAs depend on prior transcription of 3' proximal genes. We present a model for viral mRNA synthesis in vitro. PMID- 6250716 TI - Tandem repeats within the inverted terminal repetition of vaccinia virus DNA. AB - A tandemly repeated sequence within the genome of vaccinia virus is cut to fragments of approximately 70 bp by Hinf I, Taq I or Mbo II. The 70 bp repetition was localized within the much larger (10,300 bp) inverted terminal repetition by restriction analysis of cloned DNA fragments and by hybridization of the purified 70 bp repeat to vaccinia virus DNA restriction fragments. The molar abundance of the 70 bp fragment corresponds to a 30 fold repetition at each end of the genome. The repeating restriction endonuclease sites were mapped by agarose gel electrophoresis of partial Hinf I digests of the terminally labeled cloned DNA fragment. The first of 13 repetitive Hinf I sites occurred approximately 150 bp from the end of the cloned DNA. After an intervening sequence of approximately 435 bp, a second series of 17 repetitive Hinf I sites occurred. The DNA between the two blocks of repetitions has a unique sequence containing single Dde I, Alu I and Sau 3A sites. Tandem repeats within the inverted terminal repetition could serve to accelerate self-annealing of single strands of DNA to form circular structures during replication. PMID- 6250717 TI - The genome-linked protein of picornaviruses. VII. Genetic mapping of poliovirus VPg by protein and RNA sequence studies. AB - The poliovirus genome-linked protein (VPg) has been subjected to radiochemical microsequence analysis. Sequence studies of virion RNA by a modification of Sanger's dideoxy method have revealed a base sequence corresponding to the amino acid analysis. This result proves that VPg is virus-encoded. The RNA sequence has allowed us to predict the total amino acid sequence of VPg and part of its precursor. VPg is, at most, 27 amino acids long. It maps within the 3' terminal segment of the viral genome that encodes the precursor polypeptide NCVP1b for the virus-specific RNA polymerase NCVP4. PMID- 6250718 TI - Protein inhibitor of cAMP-dependent protein kinase: production and characterization of antibodies and intracellular localization. AB - Multiple forms of protein kinase inhibitor exist in mammalian testis. Specific antibodies to testicular protein kinase inhibitor (PKI) have been raised in sheep. The antibody to the smallest of the inhibitors (9300 daltons) has been purified by antigen-affinity chromatography and shown to give a precipitin band with the inhibitor by double immunodiffusion. The antibody does not recognize any of the subunits of cyclic nucleotide-dependent protein kinases, namely cGMP dependent protein kinase or the catalytic or regulatory subunits from type I or type II cAMP-dependent protein kinases. The biological activity of the 9300 dalton PKI is blocked completely by a 5 fold molar excess of antibody. Furthermore, the antibody can also block the activity of all other forms of testicular PKI. Using the antibody in indirect immunofluorescence microscopy, PKI localization was examined during interphase and mitosis in a variety of cell types. Our observations indicate that PKI is localized on microtubules in the cytoplasmic microtubule complex during interphase and in the spindle apparatus during mitosis. We suggest that PKI may play a role in the cAMP-dependent regulation of microtubule structure and/or function. PMID- 6250719 TI - Hormonal induction of differentiation in teratocarcinoma stem cells: generation of parietal endoderm by retinoic acid and dibutyryl cAMP. AB - It has previously been shown that retinoic acid induces multiple phenotypic changes in cultures of F9 teratocarcinoma stem cells. In this paper we demonstrate that these retinoid-generated cells can be converted to yet another cell type by compounds that elevate cAMP concentrations. The phenotype of the new cell type is characterized by the synthesis of plasminogen activator, laminin and type IV collagen, and by very low levels of alkaline phosphatase and lactate dehydrogenase. The secretion of plasminogen activator and type IV collagen, and low levels of alkaline phosphatase and lactate dehydrogenase, have been previously shown to be properties of parietal endoderm, an extraembryonic cell which is generated early in mouse embryonesis. We show here that parietal endoderm also synthesizes laminin. The cell type generated by retinoic acid and dibutyryl cAMP treatment is therefore indistinguishable from definitive parietal endoderm. Analysis of the final phenotype indicates that it is not dependent upon the continued presence of either compound, and that cAMP agents are active only on cells that have been treated with retinoic acid. PMID- 6250720 TI - Transmembrane location of oligosaccharide-lipid synthesis in microsomal vesicles. AB - The oligosaccharide-lipid which is the precursor of asparagine-linked oligosaccharides of eucaryotic glycoproteins is synthesized from sugar nucleotides in the endoplasmic reticulum. The transmembrane location of the assembly of this oligosaccharide-lipid has been studied in vitro in rat liver microsomes. Protease treatment of these sealed vesicles which are derived from the endoplasmic reticulum resulted in the inactivation of a number of enzymes of oligosaccharide-lipid synthesis. Three early steps, the synthesis of dolichol- phosphate--mannose, of dolichol--phosphate--glucose and of dolichol- pyrophosphoryl--di--N--acetylchitobiose, as well as the final steps, the addition of glucose residues to oligosaccharide-lipid, were inactivated under conditions where only the cytoplasmic side of the membrane was accessible to protease. This finding, and the fact that no activities were latent to protease in intact microsomal vesicles, suggest that oligosaccharide-lipid is assembled on the cytoplasmic side of the microsomal membrane. However, the possibility of enzymes spanning the bilayer with their active sites facing the lumen cannot be ruled out. These results are discussed in relation to the segregation of newly made glycoprotein products within the lumen of the endoplasmic reticulum. PMID- 6250721 TI - Mutants of vesicular stomatitis virus blocked at different stages in maturation of the viral glycoprotein. AB - Maturation of the vesicular stomatitis virus (VSV) glycoprotein (G) to the cell surface is blocked at the nonpermissive temperature in cells infected with temperature-sensitive mutants in the structural gene encoding for G. We show here that these mutants fall into two discrete classes with respect to the stage of post-translational processing at which the block occurs. In all cases the mutant glycoproteins are inserted normally into the endoplasmic reticulum membrane, receive the two-high-mannose oligosaccharides, and apparently lose the NH2 terminal signal sequence of 16 amino acids. In cells infected with one class of mutants, no further processing of the glycoprotein occurs, and we conclude that the mutant protein is blocked at a pre-Golgi stage. In cells infected with ts L511(V), however, addition of the terminal sugars galactose and sialic acid occurs normally. Thus the maturation of G proceeds through several Golgi functions but is blocked before its appearance on the cell surface. The oligosaccharide chain of ts L511(V) G, accumulated at either the permissive (where surface maturation occurs) or the nonpermissive temperature, lacks one saccharide residue, probably fucose. In addition, no fatty acid residues are added to the ts L511(V) G protein at the nonpermissive temperature, although addition does occur under permissive conditions. PMID- 6250722 TI - Expression of unselected adenovirus genes in human cells co-transformed with the HSV-1 tk gene and adenovirus 2 DNA. AB - We have introduced adenovirus 2 genes into high molecular weight DNA of permissive human cells by co-transformation of tk- human 143 cells with Ad2 restriction enzyme fragments and a cloned Bam HI fragment that carries the HSV-1 thymidine kinase gene. Tk+ cells were isolated after selection and maintenance in HAT medium. Several co-transformed lines are able to complement the growth of Ad5 dl312 (delta 1.2--3.7) and Ad5 dl434 (delta 2.6--8.7), deletion mutants that lack sequences from the left end of the viral genome. The amount and arrangement of viral sequences in the co-transformed cell lines have been analyzed by restriction endonuclease digestion and filter hybridization. Most of the cell lines contain a single insertion of the HSV-1 tk fragment and a single insert of adenoviral DNA. However, one line (B1) contains at least four different insertions, two of which are present in multiple copies. The adenoviral DNA in all cell lines is composed of sequences from the left end of the genome and extends for varying lengths in different lines. Two cell lines that complement deletion mutants efficiently synthesize both early region 1a and 1b mRNAs. The B1 line synthesizes low levels of 1a mRNA, higher levels of 1b mRNA and a unique mRNA that maps to the right of the 1b gene family. When grown continuously in HAT medium, some cell lines are quite stable while others are fairly unstable. Some tk+ subclones support the growth of viral mutants as well as the parental line while others give reduced levels of complementation. For all tk+ subclones examined, the alteration or reduction in viral gene expression is independent of changes in the pattern of integration of viral DNA. PMID- 6250723 TI - Sequence organization of cloned intracisternal A particle genes. AB - Seven recombinant DNA clones containing mouse intracisternal A particle genes were isolated and analyzed by restriction enzyme digestion, Southern blot analysis and heteroduplex mapping. The sequence organization of the individual genes was found to differ, with one end of the gene region being most variable, while a central segment of 1.8 kb was missing from two of the clones. A third region, common to all the clones and containing the 3' end of the gene, is present in about 1800 copies per haploid genome, but the central portion is found in only 650 copies. The same reiteration frequency is found in both myeloma tumor and mouse liver DNA. The most abundant intracisternal A particle RNA in two different myeloma lines was found to be 3.5 kb, and RNA/DNA hybrids show that the RNA is homologous to all but a small internal segment of one of the clones. PMID- 6250724 TI - Internal organization of the major adult alpha- and beta-globin genes of X. laevis. AB - We describe the isolation of two recombinant lambda phages, each containing genomic DNA fragments encoding both the major adult alpha- and beta-globin mRNAs of X. laevis. The DNA fragment in the two clones have restriction maps which indicate that they are each derived from a different member of the pair of alleles present in the heterozygote used as the source of DNA for cloning. The characterization of these two clones by restriction mapping, R looping and DNA sequencing shows that the alpha 1- and beta 1-globin genes lie in the orientation separated by 7.7 kb of DNA. There are two introns in the alpha 1-globin gene and two in the beta 1-globin gene, and they interrupt the genes at exactly the same positions as the introns found in all known mammalian alpha- and beta-globin genes. The exon sequences proximal to the introns show a much higher degree of homology with mammalian sequences than the sequences distal to intron/exon junctions, and the introns in the beta 1-globin gene of X. laevis are very similar in length to the corresponding introns in the beta-globin genes of several mammals and the chicken. PMID- 6250725 TI - Insertion of the Drosophila transposable element copia generates a 5 base pair duplication. AB - To examine the details of insertion for the D. malanogaster transposable element copia, we have isolated three independent pairs of genomic fragments which correspond to occupied and unoccupied target sites for insertion. Restriction endonuclease analysis suggests that sites with and without an element differ by a simple 5000 bp insertion. Direct DNA sequence analysis demonstrates that a 5 bp sequence, present once in the target DNA at the site of insertion, is found on both sides of the element after insertion. The 5 bp sequences which are duplicated are different in each case. Moreover, there does not appear to be any sequence homology among these three independent insertion sites PMID- 6250726 TI - Terminal repeats of the Drosophila transposable element copia: nucleotide sequence and genomic organization. AB - We have determined the nucleotide sequence of the terminal regions of two members of the copia sequence family of D. melanogaster. The first 276 bp at one end of a copia element are repeated in direct orientation at its other end. The direct repeats on a single copia element are identical to each other, but they differ by two nucleotide substitutions between the two elements which were examined; this suggests that during transposition only one direct repeat of the parent element is used as a template for both direct repeats of the transposed element. Each direct repeat itself contain a 17 bp imperfectly matched inveted terminal repetition. The ends of copia show significant sequence homology both to the yeast Ty1 element and to the integrated provirus of avian spleen necrosis virus, two other eucaryotic elements known to insert at many different chromosomal locations. Analysis of the genomic organization of the direct repeat sequence demonstrates that it seldom, if ever, occurs unlinked to an entire copia element. PMID- 6250727 TI - Endotoxin and macrophage-migration inhibition. PMID- 6250728 TI - Concanavalin A promotes bromodeoxyuridine induction of enodgenous C-Type virus in B cells. PMID- 6250729 TI - [Treatment of recurrent herpetic disease with specific inactive antigen]. PMID- 6250730 TI - Synthesis of salmon endorphin. PMID- 6250731 TI - Inotropic and chronotropic actions of 2-substituted and 8-substituted derivatives of adenosine 3',5'-cyclic monophosphate. PMID- 6250732 TI - Effects of saikosaponins on the metabolic actions of adrenaline, ACTH and insulin on the fat cells. PMID- 6250733 TI - Spectral interaction of 11-hydroxy-delta-8-tetrahydrocannabinol with rabbit and rat liver microsomal cytochrome P-450. PMID- 6250734 TI - Studies of the fatty acid composition and membrane microviscosity in Salmonella typhimurium TA98. AB - When the mutagen tester bacterial strain Salmonella typhimurium TA 98 was grown at different temperatures, we found that the unsaturated fatty acid composition increased at the lower growth temperatures. Membrane microviscosity, as assessed with spin-probe fatty acids using electron spin resonance, decreased as the unsaturated fatty acid content increased. These findings are of importance in understanding our recent observation that the mutagenic response of these bacteria was increased when they were grown at 27 degrees C vs. 37 degrees C, and indicate that membrane properties may play an important role in the sequence of events leading to mutagenesis. PMID- 6250735 TI - [Mesoblastic nephroma. Apropos of 6 cases]. AB - 6 cases of congenital mesoblastic nephroma removed surgically between 5 days and 2 months 1/2 of age are reported. The authors point out the peculiar histological aspect of this tumor : myomatous or fibromyomatous proliferation which surround in some places normal or dysplastic glomerular or tubular structures and penetrates by digitations in parenchymatous elements without destroying them. At the periphery of the tumor there are some lymphatic capsular ectasia or lymphoid infiltration or cartilaginous islets. In case of a renal tumor of the newborn or infant they emphasize the necessity to search for a congenital mesoblastic nephroma in order to avoid all types of radio therapic or chimiotherapic treatment without histological diagnosis. These forms of therapy are responsible for severe complications heavily impairing a prognosis which in most cases is an excellent one when nephrectomy alone is carried out. In some exceptional cases it seems useful to add other forms of therapy when the tumor proves itself to be of a peculiar aggressivity macro or microscopically. PMID- 6250736 TI - [Baroreceptors capable of inducing the biosynthesis and release of prostaglandins (PG) and of modulating adrenergic neurotransmission in the myocardium]. AB - In the isolated Rabbit heart, high pressure, on the one hand, inhibits the noradrenaline release, and on the other hand, induces both the biosynthesis and release of PGs(PGE2,PGF2 alpha) from the auricles and mainly from the right auricle i.e. where the sympathetic nerve endings are the most numerous. Therefore, high pressure, by a negative feedback process, plays a great part in moderating the adrenergic neurotransmission responsible for the hypertension. These effects result from a supplementary pressure which acts on the walls of coronary arteries and arterioles and modifies their distensibility. It thus appears that in the walls of arteries and arterioles there are baroreceptors which are sensitive to the pressure variations in order to regulate adrenergic neurotransmission, by means of a reflex path still unknown. PMID- 6250737 TI - Evidence for uncoupling of the beta receptor-adenylate cyclase complex. PMID- 6250738 TI - Effect of phospholipid methylation on beta-adrenergic receptors in the normal and hypertrophied rat myocardium. AB - Abdominal aortic constriction in rats results in mild cardiac hypertrophy (20% increase in left ventricular weight compared to sham-operated controls) which is associated with increased numbers of beta-adrenergic receptors (123 +/- 7.3 fmol/mg protein (mean +/- SE) vs. 87 +/- 4.3 fmol/mg in controls, P < 0.01) without changes in their affinities for dihydroalprenolol. In vitro synthesis of phosphatidylcholine through successive methylation of phosphatidylethanolamine by S-adenosyl-L-methionine is enhanced in the hypertrophied myocardium) 0.38 +/- 0.03 nmol/mg per 30 minutes vs. 0.23 +/- 0.03 nmol/mg per 30 minutes in controls, P < 0.01). In both experimental groups, methyltransferase activity has a high affinity for S-adenosyl-L-methionine (Km = 6.8 microM), depends on Mg2+, is optimal around pH 9.0, and is inhibited by S-adenosyl-L-homocysteine (ki = 8.3 microM). The possible relationship between phospholipid methylation and changes in myocardial beta-adrenergic receptors was studied in both normal and hypertrophied hearts. Preincubation of cardiac membranes with S-adenosyl-L methionine increased the numbers of b eta-adrenergic receptors in proportion to the duration of incubation and the concentration of S-adenosyl-L-methionine. In both groups, S-adenosyl-homocysteine, but not 5'-AMP or L-methionine, attenuated the increase in beta-adrenoreceptors. These results indicate that phospholipid methylation may be an important mechanism for regulation of beta-adrenergic mechanisms in both normal and hypertrophied myocardium. PMID- 6250740 TI - Rapid preparation of nucleotides from acid-soluble pools by chromatography on silica, as exemplified with acid extracts of cultured cells. AB - A rapid technique (5-10 min) has been developed for fractionating nucleotides from base and nucleoside contaminants in acid extracts of cells, by adsorption to silica gels. Silica gels (1-mL bed volume) were washed with 5 mL of water then with 5 mL of acetonitrile/water (90/10 by vol). After applying 3-mL samples, adjusted to 900 mL/L acetonitrile content, we washed the gel with an additional 10 mL of the acetonitrile/water solvent. More than 95% of the amounts of bases and nucleosides prsent, except for cytidine (92%), did not adsorb to silica under these conditions. Nucleotides were then quantitatively eluted with 9 mL of water. The retention volumes for positive, negative, and neutral nucleic acid components have been determined, to investigate the discriminatory properties of nucleic acid components on silica. Compounds (bases, nucleosides) that are not ionized at pH 7 do not bind to silica. However, negative, positive, and zwitterionic compounds are tightly adsorbed to the silica gels. This procedure has been used to purify nucleotides from several normal and transformed cell lines. PMID- 6250739 TI - Therapeutic implications of slow-channel blockade in cardiocirculatory disorders. PMID- 6250741 TI - Diagnosis of viral infections by multicomponent mass spectrometric analysis. AB - Metabolic profiles of urine extracts of humans with viral infections, as well as of media of virus-infected human tissue cultures, have been analyzed by non fragmenting mass spectrometry and compared with corresponding controls. The spectra were then subjected to several alternative computerized statistical procedures to detect diagnostic biochemical profiles. Controlled longitudinal studies on fully informed, consenting volunteers who received sandfly fever virus demonstrate the onset of a characteristic metabolic pattern that precedes the onset of symptoms and subsides when the patients overcome the infection. Longitudinal studies of human tissue cultures infected with poliomyelitis virus demonstrate characteristic metabolic patterns within a few hours after infection. Non-fragmenting mass spectrometry may thus provide the clinical laboratory with a sensitive, reliable test for viral infections significantly faster than attainable by current techniques. PMID- 6250742 TI - Microenzymatic assays for lysosomal enzymes in primary amniotic fluid cell cultures. AB - A study of three lysosomal enzymes (hexosaminidase, beta-galactosidase and alpha galactosidase) in normal primary amniotic fluid cell cultures using a microenzymatic assay is presented. No difference in enzyme activity was found between primary and amniotic cell cultures in passage number one. A progressive change in the proportions of hexosaminidase A and hexosaminidase B with time was demonstrated in culture. The feasibility of this procedure for the early prenatal diagnosis of disorders due to lysosomal enzyme deficiency is discussed. PMID- 6250743 TI - The estimation of vitamin D and some metabolites in human plasma by mass fragmentography. AB - A mass fragmentographic assay for vitamin D3, 25-hydroxyvitamin D3, 25 hydroxyvitamin D2 and 24,25-dihydroxyvitamin D3 is described. After extraction of plasma with methanol and dichloromethane, Lipidex 5000 chromatography was used to separate the plasma extract into three fractions (a vitamin D fraction, a 25 hydroxyvitamin D fraction and a 24,25-dihydroxyvitamin D fraction). Cholesterol was removed from the vitamin D fractio by thin-layer chromatography. :After addition of vitamin D2 to each fraction, isotachysterol trimethylsilyl ethers were formed. Recoveries prior to gas chromatography-mass spectrometry were assessed by the use of tritiated standards added to the plasma before extraction. Using this procedure, normal ranges were established (vitamin D3: 3--17.7, 25 hydroxyvitamin D3: 5.9--35.2, 25-hydroxyvitamin D2: 0.6---1.0 and 24,25 dihydroxyvitamin D3: 0.6--2.9 micrograms/l). PMID- 6250744 TI - Extraction of cyclic AMP for the determination in the competitive protein binding assay. PMID- 6250745 TI - Effect of sulfhydryl reagents on the enzymatic activity of human renin: implications for renin assay. AB - Sulfhydryl (SH) reagents are sometimes used in renin assays, yet their effects on the enzymatic activity of human renin are not clearly understood. We have employed radioimmunoassay of angiotensin I (AI) to assess the effects of dithiothreitol (DTT) and of dimerecaptopropanol (DMP) on the formation of AI at pH 5.5 and at pH 7.4. When ethylenediamine tetra-acetate, phenylmethylsulfonyl fluoride, and 8-hydroxyquinoline were used as angiotensinase inhibitors, both DTT and DMP decreased the rate of AI formation in each of two human plasma pools at both pH values. In contrast, in a system of semi-purified human kidney renin and hog renin substrate, DTT enhanced the formation of AI, increasing Vmax without changing Km at both pH values. The reaction of human kidney renin with synthetic tetradecapeptide renin substrate was stimulated by DTT at pH 7.4 but inhibited by DTT at pH 5.5. In all three systems, SH reagents altered the ratio of reaction velocity at pH 5.5 to reaction velocity at pH 7.4. We conclude that SH reagents affect the assay of human renin in complex ways which depend upon the pH of incubation and upon the subcomplex ways which depend upon the pH in incubation and upon the substrate utilized. Although the mechanism of these effects is not known, such effects probably contribute to the lack of agreement among many of the procedures for renin assay. PMID- 6250746 TI - Serum ferritin in patients with cancer: determination with antibodies to HeLa cell and spleen ferritin. AB - Some malignant tissues and cell lines contain acidic isoferritins and it has been suggested that the assay of such isoferritins in serum may be of value in the diagnosis of malignancy. This paper describes a radioimmunoassay for acidic ferrtin purified from HeLa cells. Examiniation of purified heart, kidney, liver and spleen ferritin showed that the assay was highly specific for acidic isoferritins. Ferritin concentrations have been measured with antibodies to HeLa cell and spleen ferritin in extracts of normal and tumour tissue. Although the tumours contained more HeLa type ferritin than the corresponding normal tissue the HeLa/spleen type ferritin ratio was low. HeLa-type ferritin concentrations have been compared with values obtained with anti-spleen ferritin in over 1000 sera from normal subjects and patients with cancer and leukaemia. HeLa-type ferritin as not detected ( less than 2 micrograms/l) in most normal sera. Concentrations of up to 53 micrograms/l were found in sera from patients with malignant disease but the HeLa/spleen type ferritin ratio was always very low. There appears to be little application for antibodies to HeLa cell or heart ferritin in the diagnosis or monitoring of cancer. PMID- 6250747 TI - Pitfalls in the radioactive method of galactose-1-phosphate uridyltransferase activity measurement. PMID- 6250748 TI - Intraparotid haemangioma in an adult: case report and review of the literature. AB - Capillary haemangiomas are among the common benign tumours of the parotid during infancy and childhood. Cavernous haemangiomas are rare lesions in the adult parotid. A cavernous haemangioma of the parotid is described in a 63-year-old woman. The literature is reviewed and the adult and childhood haemangiomas of the parotid are compared. PMID- 6250749 TI - Lymphocyte 5'-nucleotidase deficiency in hypogammaglobulinemia: clinical characteristics. PMID- 6250750 TI - Immune response to polyoma tumor cells in mice. II. Antibody-dependent cell mediated cytotoxicity with embryonic and polyoma specificity. PMID- 6250751 TI - Hypothalamic-pituitary-adrenal (HPA) function in adrenocortical steroid treated minimal change nephrotic syndrome. AB - Seventeen children aged 1.5 to 15.6 years with minimal change nephrotic syndrome (MCNS) had hypothalamic-pituitary-adrenal (HPA) tests performed. The study consisted of baseline cortisol levels (8 a.m. and 4 p.m.), 6-hour ACTH stimulation tests and metyrapone tests. Ten patients were frequent relapsers (4 or more relapses per year) and 7 patients were infrequent relapsers (less than 4 relapses per year). All relapses were treated with daily prednisone 60 mg/m2 until the urine was protein-free for 3 days followed by prednisone 40 mg/m2 every other day for 28 days. All were tested no sooner than 1 week after alternate-day prednisone therapy was discontinued. The morning and afternoon cortisol levels of all frequent relapsers were abnormally low. The average a.m. and p.m. cortisol levels in the frequent relapsers were 2.6 +/- 0.08 and 1.4 +/- 0.4 microgram/dl respectively (normal a.m. value 10-20 microgram/dl, p.m. 50% a.m. value). In the frequent relapsers 9 out of 10 had a normal 6-hour ACTH test and 8 out of 9 had a normal response to metyrapone. In all infrequent relapsers the morning and afternoon cortisols were normal (mean a.m. 12.9 +/- 1.4 and p.m. 6.8 +/- 0.8 microgram/dl). Also, all infrequent relapsers had normal responses to ACTH and metyrapone. It is concluded that low baseline plasma cortisol levels are predictably present in frequent relapsers treated with prednisone. PMID- 6250752 TI - Foregut apudomas in Zimbabwe-Rhodesian Africans. PMID- 6250753 TI - Ganglion migrans of the proximal tibiofibular joint causing lesions in the subcutaneous tissue, muscle, bone, or peroneal nerve: report of three cases and review of the literature. AB - Three cases illustrate the variety of ways a ganglion may arise from the tibiofibular joint. In one case, the diagnosis was initially obscure because the swelling occurred under the muscles of the lateral compartment of the lower leg; the lesion was also intraosseous and extended into a tendon. In the second case, the ganglion had invaded the peroneal nerve, and in the third, the ganglion was a palpable subcutaneous tumor. PMID- 6250754 TI - Recent advances in the understanding of the metabolism and functions of vitamin D. AB - Many advances have been made in the past several years in our understanding of the metabolism and mechanism of action of vitamin D. Recognition of the clinical implications of this knowledge continues to grow. Despite these gains, however, many questions remain unanswered. These include the role of 24,25(OH)2D3 in physiologic processes, the nature of the contribution of vitamin D metabolism to bone growth and development, the responses of other possible target tissues such as the pancreas and parathyroid gland, and the further elucidation of interactions between vitamin D metabolites and parathyroid hormone in the maintenance of calcium and phosphorus homeostasis. The next decade of research is bound to bring insight into these and other questions. PMID- 6250755 TI - [Subacute sensory neuropathy associated with lung cancer (author's transl)]. PMID- 6250756 TI - [Experimental ethambutol neuropathy-comparison between short-term administration of large dose and long-term administration of small dose- (author's transl)]. PMID- 6250757 TI - [Marinesco-Sjogren syndrome associated with peripheral nerve involvement--report of three cases in a family (author's transl)]. PMID- 6250758 TI - Availability of immunobiologic agents and antiparasitic drugs from CDC. PMID- 6250759 TI - Dose response in captopril therapy of hypertension. AB - Dose-response curves of blood pressure and of the biochemical components of the renin-angiotensin-aldosterone system were determined during long-term treatment with captopril in 21 hypertensive patients. Captopril was given in biweekly, doubling doses starting with 25 mg 3 times a day until control of blood pressure was achieved or a total daily dosage of 600 mg was reached. Recumbent and standing systolic and diastolic blood pressure fell on 75 mg captopril daily. Increasing the captopril dose did not induce further significant hypotensive effects. The pretreatment level of plasma renin activity (PRA) was a poor predictor of the hypotensive effect of captopril. The rises in PRA and plasma angiotensin I level (PA I) and the decrease in plasma angiotensin II level (PA II) and plasma aldosterone level (PAC) provide biochemical evidence for angiotensin-converting enzyme (ACE) inhibition in vivo. These effects were present on daily doses of 75 to 150 mg captopril. PMID- 6250760 TI - Plasma delta-9 tetrahydrocannabinol concentrations and clinical effects after oral and intravenous administration and smoking. AB - Delta-9-tetrahydrocannabinol (THC) was given intravenously, by smoking, and by mouth to 11 healthy subjects. Plasma profiles of THC after smoking and intravenous injection were similar whereas plasma levels after oral doses were low and irregular, indicating slow and erratic absorption. Based on AUC0-360 min systemic availability of THC after smoking was estimated to be 18 +/- 6%. Oral THC in a chocolate cookie provided systemic availability of 6 +/- 3%. Of the two major clinical signs of cannabis intoxication, reddened conjunctivae persisted for as long as THC levels were above 5 ng/ml, and tachycardia was a less reliable measurement of prevailing THC levels or "high." The time courses of plasma concentrations and clinical "high" were of the same order for intravenous injection and smoking, with prompt onset and steady decline over a 4-hr period. The appearance of "high" lagged behind the increase in plasma concentrations, suggesting that brain concentrations were increasing as plasma concentrations decreased. After oral THC, the onset of clinical effects was much slower and lasted longer, but effects occurred at much lower plasma concentrations than after the other two methods of administration. PMID- 6250762 TI - Poisoning with 4-aminopyridine: report of three cases. AB - Four-aminopyridine is an acutely toxic avicide considered by the manufacturer to be a bird "repellant" because only a small number of birds are acutely poisoned, become disoriented, and emit a distress cry frightening other members of the flock. Four-aminopyridine dramatically enhances transmission at the neuromuscular junction and other synapses, and has been employed clinically in the treatment of prolonged paralysis caused by antibiotics and muscle relaxants, and in the Eaton Lambert syndrome. In this paper we report the results of an acute poisoning misadventure in three adult males. We review the animal toxicology, summarize the neurophysiological research using 4-AP as a potassium channel blocker, comment on clinical applications, and outline the management of overdose with this agent. PMID- 6250761 TI - Endocrine profile in the long-term phase of converting-enzyme inhibition. PMID- 6250763 TI - The evaluation of hypoglycemia. PMID- 6250764 TI - Endocrine disorders. Introduction. PMID- 6250765 TI - Simultaneous parathyroid and pharyngeal tumors with normal PTH and NcAMP. PMID- 6250766 TI - Gynecologic oncology: cancer update (second of two parts). PMID- 6250767 TI - Metabolic control mechanisms in precancerous liver. PMID- 6250768 TI - Development of radiographic abnormality in chrysotile miners and millers. PMID- 6250769 TI - Toxicity and tolerance of 9-(2-hydroxyethoxymethyl)guanine. AB - Acyclovir [9-(2-hydroxyethoxymethyl)guanine] is a new antiviral agent which has specific activity in virus-infected cells. The drug has a high therapeutic index in animal and laboratory models but had not been tested for toxicity in human eyes at the time of this study. A randomized double-blind study on patients requiring antiviral therapy for treatment or prophylaxis of herpetic ocular infections revealed minimal irritation associated with topical administration. Further controlled studies will be necessary to evaluate this compound's clinical efficacy. PMID- 6250770 TI - [Liver transplantation]. PMID- 6250772 TI - [After-care in the hospital. Tasks and solutions from a surgical viewpoint]. PMID- 6250771 TI - [Blunt dissection of the esophagus]. AB - The operative technique of blunt dissection of the esophagus is described, in which opening the thorax to remove the total esophagus is not necessary. This procedure is indicated in carcinoma of the laryngopharynx and carcinoma of the proximal and distal third, in lye strictures, and scleroderma of the esophagus. Blunt dissection is advantageous because it contains less risk compared to operations with opening of the pleural and abdominal cavities. In malignomas blunt dissection can be more radical than tumor resection. For esophageal replacement we used the stomach, which was transformed into a tube supplied by the right gastric arteries. PMID- 6250773 TI - Mineral and vitamin status on high-fiber diets: long-term studies of diabetic patients. AB - High-fiber diets have a beneficial impact on glucose metabolism of selected persons with diabetes mellitus. A major concern is the long-term effects of fiber intake on mineral and vitamin status. We measured serum concentrations of selected minerals and vitamins and also assessed three fat-soluble vitamins in 15 patients fed high-fiber diets for an average of 21 mo. Average values for serum calcium, phosphorus, alkaline phosphatase, iron-binding capacity, magnesium, and hemoglobin values were normal. Vitamin B12 and folic acid concentrations in serum were also normal. Indirect assessment suggested that these patients had adequate intakes of the fat-soluble vitamins A, D, and K. These preliminary observations suggest that high-fiber diets containing a wide variety of natural foods are well tolerated for up to 51 mo; we failed to detect evidence suggesting mineral or vitamin deficiency in these patients. PMID- 6250775 TI - [Effect of membrane potential, and extra- and intracellular verapamil concentrations on the inward ion current of dialyzed Helix pomatia neurons]. PMID- 6250774 TI - Glucose tolerance and blood lipids in bran-fed patients with impaired glucose tolerance. AB - Thirty-eight patients (13 men and 25 women) with impaired glucose tolerance, aged 33--70 yr, underwent a dietary program adding 20 g of raw bran to their usual diet without changing their dietary habits. After 1 mo of treatment, the areas under the curves for glucose and insulin were reduced from 26,214 +/- 5618 to 24,529 +/- 5207 g/min (P < 0.001) and from 15,893 +/- 9714 to 12,440 +/- 7377 mU/min (P < 0.001), respectively, cholesterol was reduced from 234 +/- 40 to 212 +/- 29 mg/dl (P < 0.001), and triglycerides were reduced from 108 +/- 56 to 97 +/ 50 mg/dl (P < 0.05). Body weight (initially 128.44% relative body weight) decrease 0.8% (P < 0.02). After the first month, 14 subjects were studied for a further 2 mo. Six patients continued bran feeding, and eight, who stopped bran, were used as controls. Patients who took bran maintained metabolic improvement over the 3-mo treatment period, while those who stopped bran did not. PMID- 6250776 TI - [Enzyme activity in sections of kidney cortex cells]. PMID- 6250777 TI - [Preferential development of flexion of the left or right hindlimb as a result of treatment with methionine-enkephalin or leucine-enkephalin, respectively]. PMID- 6250778 TI - [New DNA modification-restriction plasmid system detected in a clinical strain of Escherichia coli]. PMID- 6250780 TI - [Oxygen as an inducer of calcium ion transport across lipid bilayer membranes]. PMID- 6250779 TI - [Supersynthesis of EcoRII endonuclease and methylase by strains of Escherichia coli containing recombinant plasmids obtained in vitro]. PMID- 6250781 TI - [Production of physiologically active angiotensin I, a product of synthetic gene expression in Escherichia coli cells]. PMID- 6250782 TI - [Alcohol-induced Cushing's syndrome: case report (author's transl)]. AB - Reversible Cushing's syndrome with typical physical appearance and increased basal plasma-cortisol level developed in a 48-year-old man with essential arterial hypertension, as a result of chronic alcohol abuse and could not be supressed by prolonged dexamethason inhibition. Alcohol abstinence within a few weeks produced remission with normal adrenocortical function and regulation without any other therapeutic measures. Renewed alcohol consumption quickly brought about again the alcohol-induced Cushing's syndrome. An abnormality of central regulation with inadequate ACTH secretion was the cause of the hypercortisolism. Previously reported cases of alcohol-induced Cushing's syndrome are not uniform: in some the diagnosis is in doubt. PMID- 6250783 TI - [Demonstration of Epstein-Barr virus genome in european Burkitt lymphoma (author's transl)]. AB - A 6-year-old European boy with a tumour in the head and neck region died 86 days after the first occurrence of symptoms despite chemo- and radiotherapy. An epipharyngeal biopsy at the beginning of the disease and a cytological investigation of biopsy and autopsy material showed non-Hodgkin lymphoma with a high degree of malignancy of the Burkitt type. High antibody titres against Epstein-Barr virus (EBV)-specific virus capsid antigen, nuclear antigen and the R component of the EBV-early-antigen-complex as well as the approximately 27 EBV genome equivalents per tumour cell, demonstrated by DNA-DNA hybridisation, characterised the tumour as true Burkitt lymphoma which is observed extremely seldom outside Africa. PMID- 6250784 TI - [Diagnosis of hypercalciuria in calcium nephrolithiasis (author's transl)]. AB - An increased calcium excretion in 24-hour urine was found in 32 of 42 out patients with recurrent calcium nephrolithiasis (calcium excretion > 300 mg in males, > 250 mg in females). Subsequent hospitalization of the 32 patients revealed the following diagnosis after a calcium tolerance test: absorptive hypercalciuria in 18, renal hypercalciuria in 4, primary hyperparathyroidism in 2 and dietary hypercalciuria in 7. Normocalciuria in 10 out-patients was confirmed in 6; in one instance there was, however, primary hyperparathyroidism, in 3 there was absorptive hypercalciuria. In one patient it was not possible to classify the hypercalciuria. Total as well as nephrogenic cAMP showed wide scatter and was unsuitable, therefore, in differential diagnosis. In 2 of 3 cases of hyperparathyroidism the serum level of parathormone was distinctly elevated. PMID- 6250785 TI - Epidemiology of acute gastroenteritis in early childhood in Kenya. V. An inverse relationship between the peak age-incidence and the waning of rotavirus maternal antibodies. PMID- 6250786 TI - Malignant tumours of the breast in Northern Savannah of Nigeria. PMID- 6250787 TI - [Electrophysiology of peripheral, non-traumatic facial paralysis]. PMID- 6250788 TI - [Electromyographic studies in 131 cases of traumatic paralysis of the brachial plexus]. PMID- 6250789 TI - The regulation of de novo synthesis of cholesterol in the human fetal adrenal gland by low density lipoprotein and adrenocorticotropin. PMID- 6250790 TI - Metabolism of low density lipoprotein by human fetal adrenal tissue. PMID- 6250791 TI - Follicle-stimulating hormone-mediated induction of functional luteinizing hormone/human chorionic gonadotropin receptors during monolayer culture of porcine granulosa cells. AB - The LH/hCG receptor content of porcine ovarian granulosa cells from 1- to 3-mm follicles can be increases to 4--5 times the preculture level during monolayer culture in serum-containing media supplemented with insulin and FSH. The binding of [125I]iodo-hCG declines during the first 2 days of culture, but then uniformly increases through 6 days, achieving a 14- to 15-fold increase relative to the 2 day level under optimal conditions. Analysis of receptor binding by autoradiography indicates that after 2 days, the number of cells specifically binding [125I]iodo-hCG increases significantly during culture, as does the intensity of binding on receptor-bearing cells. Granulosa cells in monolayer culture exhibit heterogeneous receptor induction, indicating that normalized [125I]iodo-hCG binding data cannot be used to estimate receptor concentration per cell. Receptor affinities in the initial and induced populations are identical. LH/hCG receptors induced in granulosa cells during culture are functional, as demonstrated by specific hCG-stimulated progesterone secretion. 17 beta-Estradiol produces a differential effect in vitro, generally increasing [125I]iodo-hCG binding with respect to FSH-induced levels but consistently depressing the subsequent hCG-stimulated steroidogenic response of cells bearing the induced receptor. The porcine granulosa cell monolayer system thus appears to be a useful model with which to study, in vitro, mechanisms of steroid and gonadotropin regulation of granulosa cell differentiation and overall follicular development. PMID- 6250792 TI - Uremia decreases nuclear 3,5,3'-triiodothyronine receptors in rats. AB - The maximal binding capacity (MBC) of hepatic T3 nuclear receptors was decreased in uremic rats (132 +/- 37 fmol/mg DNA) compared to sham-operated controls (212 +/- 44 fmol/mg DNA; P < 0.025), while the equilibrium affinity constants (Ka) remained unaltered (1.8 +/- 0.4 and 1.5 +/- 0.3 X 10(9) M-1 in the uremic and control rats, respectively, P = NS). There was also a reduction in the MBC of the kidney T3 receptors, from 73 +/- 14 fmol/mg DNA in the control animals to 32 +/- 7 fmol/mg DNA in the uremic rats (P < 0.10), while the Ka values were identical in both groups (1.9 +/- 0.5 X 10(9) M-1). In addition, there were significant reductions in serum T4 (1.5 +/- 0.7 microgram/dl) and T3 (92 +/- 10 ng/dl) in the uremic rats compared to control rats, whose T4 levels averaged 4.4 +/- 0.1 microgram/dl (P < 0.005) and whose T3 levels averaged 140 +/- 13 ng/dl (P < 0.005). Further, insulin levels averaged 83 +/- 21 microU/ml in uremic rats and 38 +/- 7 microU/ml in control rats (P < 0.025), while glucagon levels averaged 457 +/- 114 pg/ml in the uremic rats and 101 +/- 30 pg/ml in the control animals (P < 0.0125). These data suggest that 1) in addition to starvation and hepatectomy, uremia is another pathological condition associated with the modification of the number of T3 receptors, 2) the reduction in MBC observed may be generalized rather than organ specific for hepatic nuclear receptors, and 3) elevated glucagon levels are associated with reduced MBC in uremia, but it is indeterminate whether hyperglucagonemia is the etiology of the decrease. PMID- 6250793 TI - Characterization of gonadotropin-releasing hormone receptors in cultured rat pituitary cells. AB - The properties of gonadotropin-releasing hormone (GnRH) receptors were analyzed in isolated pituitary cells prepared by enzymatic dispersion with trypsin or collagenase-hyaluronidase. The initial impairment of LH responses to GnRH in isolated cells prepared by both methods was reversed during culture for 2 days in multiwell vessels. However, specific binding sites for GnRH, assayed by equilibration with [125I]iodi0[D-Ser(t-BU)6]des-Gly10-GnRH N-ethylamide (GnRH-A) were demonstrable in collagenase-dispersed cells, both initially and after 2 days in culture. Cellular uptake of GnRH-A was temperature dependent, with rapid and saturable binding to a limited number of specific receptor sites with high affinity for the labeled analog (Ka = 4.0 +/- 0.8 X 10(9) M-1). These sites showed common binding specificity for GnRH-A and the native GnRH peptide, with significantly lower affinity for the natural peptide (Ka = 2.3 X 10(7) M-1). Other protein and peptide hormones, including ovine LH, ovine PRL, hCG, TRH, somatostatin, and angiotensin II (up to 10(-6) M) did not inhibit binding of GnRH A to its receptors. Cellular binding of GnRH-A was followed by increased cGMP production and LH release within 10 min. The analog was 50 times more potent than native GnRH in stimulating LH release. The Kact values derived for GnRH and GnRH A were 0.5 and 0.01 nM, respectively, considerably lower than the Kd values of 50 and 0.25 nM derived from receptor binding analysis. These results indicate that GnRH receptors can be identified in isolated pituitary cells, in which peptide binding is followed by increased cGMP production and LH release. The impaired LH responses in acutely dispersed pituitary cells are not due to the loss of receptor sites but to a reversible postreceptor defect. Occupancy of about 20% of the GnRH-binding sites elicits a near-maximal LH response, indicating the nonlinearity of GnRH-receptor coupling to secretory responses in the cultured gonadotroph. PMID- 6250794 TI - Role of internalization and degradation in the removal of receptor-bound human chorionic gonadotropin in rat luteal cells in vivo. PMID- 6250795 TI - Somatogenic receptors of rat liver: regulation by insulin. AB - Somatogenic (i.e. GH) receptors have been studied on liver microsomal membranes from male and female rats. Tracer bovine GH was displaced from its binding sites by GHs of various species, but was displaced only weakly by PRLs. Specific bovine GH binding was 3.5-fold higher to female rat liver membranes than to membranes from males. Streptozotocin-induced diabetes significantly reduced binding, by 80% in females and 50% in males, while insulin therapy to normalize weight gain reversed the decrease in binding. Competitive binding curves were consistent with two independent classes of binding site: low affinity sites with K equal to 0.5 nm-1 in both sexes, and high affinity sites with K equal to 12.1 nm-1 in males and 21.4 nm-1 in females (P less than 0.001). The addition of excess ovine PRL caused a substantial loss of high affinity binding with little loss in the low affinity region, suggesting a weak somatogenic role for ovine PRL. In diabetic animals, low affinity sites were unchanged from normal, while high affinity sites were decreased in number, with no change in affinity, and restored on insulin therapy. Serum immunoreactive rat GH levels were the same in normal and diabetic, male and female animals. These studies suggest that the apparent hepatic resistance to GH seen in diabetes when liver somatomedin release is low despite normal serum GH might be explained by the loss of GH receptors in this condition. PMID- 6250796 TI - Use of an octadecylsilica purification method minimizes proteolysis during isolation of porcine and rat relaxins. AB - Previous attempts to purify relaxin from pregnant sow and rat ovaries have led to the identification of multiple components with very similar molecular weights (around 6000 daltons) and similar, but not identical amino acid compositions. It has been unclear whether these multiple forms of relaxin represented different allelic forms (isohormones), intermediates in a prohormone-hormone conversion, different hormones in their own right responsible for effects on different target tissues, or degradation products. We have applied a purification system using adsorption to small octadecylsilica (ODS) columns to reduce drastically the degree of heterogeneity. Both pig and rat relaxins are isolated as single major components with defined amino acid sequences and with minimal contamination by other molecular forms. These findings indicate that the relaxin heterogeneity previously observed is due to proteolysis of a single major stored form during conventional isolation procedures. PMID- 6250797 TI - Gonadotropin-releasing hormone and its agonist inhibit testicular luteinizing hormone receptor and steroidogenesis in immature and adult hypophysectomized rats. AB - The direct effect of gonadotropin-releasing hormone (GnRH) and its agonist on testicular LH receptor and steroidogenesis was studied in hypophysectomized immature and adult rats. Hypophysectomized rats were treated daily with varying doses of GnRH or [des-Gly10,D-Leu6(N alpha Me)Leu7, Pro9-NHEt]GnRH(a potent agonist). Some animals were also treated concomitantly with FSH, PRL, GH and/or LH to prevent the hypophysectomy-induced loss of testicular LH receptor and steroidogenic capacity. At the end of 5 days of treatment, testicular LH/hCG receptor concentration was measured by a [125I]-hCG-binding assay and steroidogenic responsiveness was determinded by in vitro incubations. GnRH and the GnRH agonist reduced testicular LH receptor in control and FSH-treated hypophysectomized immature rats. As little as 0.5 microgram agonist/day induced a greater than 40% decrease in the LH receptor content, whereas GnRH was less potent, with 50 micrograms/day inducing about a 50% decrease. The inhibitory effect of GnRH was shown to be the result of decreases in the concentration of LH receptor rather than changes in the receptor affinity (Kd = 1.1 X 10(-10)M). GnRH did not interfere with the [125I]hCG receptor assay. Treatment with PRL, GH, and FSH, alone or in various combinations, increased the testicular LH receptor content. The stimulatory effect of these pituitary hormones was depressed by concomitant treatment with the GnRH agonist. Similar inhibitory effects of GnRH and the agonist on testicular LH receptor were demonstrated in adult hypophysectomized rats. In vitro studies demonstrated that treatment with the GnRH agonist in vivo inhibited both basal and hCG-stimulated androgen production in FSH-primed immature hypophysectomized rats. Associated with decreases in androgens (testosterone and androstenedione) and reduced androgens (dihydrotestosterone, androstanediol, and androsterone), there was marked suppression of 17 alpha-hydroxylated precursors and C-21 steroid intermediates in animals treated with the GnRH agonist, thus suggesting that the inhibitory effect of the GnRH agonist was associated with possible defects in 17 alpha-hydroxylase and side-chain cleavage enzymes. Likewise, treatment with the GnRH agonist inhibited in vitro testicular steroidogenic responses in adult hypopysectomized rats. These results demonstrate the extrapituitary inhibitory effect of GnRH on testicular LH receptor content and Leydig cell steroidogenesis in immature and adult hypophysectomized rats. PMID- 6250798 TI - Dependency of acetylcholine-induced insulin release on Ca++ uptake by rat pancreatic islets. AB - The dependency of acetylcholine-induced insulin release on Ca++ uptake from extracellular fluid has been investigated in isolated rat pancreatic islets. Islets were maintained for 46 h in tissue culture, and 45Ca++ uptake and insulin release were measured over 5 min on the same batches of islets. Acetylcholine (10(-10)--10(-6) M) at 2.8 mM glucose stimulated insulin release and Ca++ uptake. Both effects were inhibited by atropine. When acetylcholine-stimulated Ca++ uptake was inhibited by verapamil, a blocker of the voltage-dependent Ca++ channel, acetylcholine-induced insulin release was abolished. In a previous report, verapamil did not inhibit glucose-stimulated insulin release over 5 min despite inhibition of the accompanying Ca++ uptake. Glucose (16.7 mM) stimulated insulin release to a similar extent as acetylcholine. Acetylcholine further enhanced glucose-stimulated insulin release without changing glucose-stimulated Ca++ uptake. Acetylcholine did not significantly alter cAMP levels in the islets. It is concluded that acetylcholine, in contrast to glucose, appears to stimulate the early phase of insulin release by enhancing Ca++ uptake from extracellular fluid. An additional effect of acetylcholine in the presence of high glucose may be operative. PMID- 6250799 TI - Multiple inhibitory actions of luteinizing hormone-releasing hormone agonist on luteinizing hormone/human chorionic gonadotropin receptor-mediated ovarian responses. AB - The administration to female rats of the LHRH agonist, [des-GlyNH2(10)]LHRH ethylamide, as either a single dose or repeated injections resulted in a decrease in the binding of 125I-labeled hCG to ovarian plasma membranes. An ovarian cell suspension prepared from the agonist-injected group of rats also responded to hCG with a decreased ability to accumulate cAMP and progesterone compared with the saline-treated controls. The receptor loss was due to a decreased number of hormone-binding sites rather than to a change in the affinity of the receptor for the hormone. Preincubation of ovarian cells with the agonistic analog in vitro also caused an inhibition of progesterone synthesis in response to hCG, cholera toxin, and 8-Bromo-cAMP, suggesting a direct inhibitory effect of the analog on ovarian steroidogenesis. Prior exposure to the agonistic analog, however, had no effect on cAMP accumulation by the ovarian cells in response to either hCG or cholera enterotoxin, further suggesting that the site of inhibitory action lies at a point after cAMP accumulation. In summary, the present study demonstrates that 1) the inhibition of ovarian steroidogenesis observed in response to the injection of the LHRH agonist is primarily due to down-regulation of ovarian hCG/LH receptors with a resultant decrease in cAMP accumulation, and this effect may be caused by the pulses of LH release from the pituitary, and 2) the direct inhibitory effect on steroidogenesis observed under in vitro conditions is independent of gonadotropin receptor, and the site of this inhibitory action lies at a point after cAMP accumulation. PMID- 6250800 TI - Serially transplantable chemically induced rat islet cell tumor. AB - A serially transplantable, chemically induced pancreatic islet cell tumor was developed in Lewis rats. The original tumor was induced by the administration of streptozotocin and nicotinamide. It was subsequently maintained by ip or sc transplantation of tissue fragments into recipient animals. Tumors generally grew to 0.5--2.0 cm in diameter within 3--4 months of transplantation. They were well encapsulated, without gross evidence of metastasis. Peroxidase immunocytochemical staining revealed a predominance of insulin-positive cells. Somatostatin-positive cells were also present and varied widely in numbers between different tumors. In addition, small numbers of glucagon-positive cells were observed in all of the tumors. On electron microscopy, cells containing secretory granules, indistinguishable from nonneoplastic beta-cells, were most abundant. Other granulated cells were also observed, but the granule morphology was not identical to that of any of the other classically described islet cell types. Tumor extracts contained an average of 3260 micrograms insulin, 22.6 micrograms somatostatin, and 0.84 micrograms glucagon per g wet wt of tissue. Tumors caused marked, progressive hypoglycemia in recipients, with plasma glucose levels frequently falling below 30 mg/dl before death. Furthermore, the recipients' islets were markedly reduced in size due to a decreased beta-cell volume. PMID- 6250801 TI - Organization of the lateral hypothalamus for control of adrenocorticotropin release in the cat. AB - Regions in the ventral midbrain that project to the lateral hypothalamus have been implicated in the control of ACTH release. To define further those areas in the lateral hypothalamus through which afferent signals might pass, we electrically stimulated 188 sites in the lateral hypothalamus of 20 cats anesthetized with chloralose-urethane. Stimulations were monophasic pulses of DC (200 microA; 0.2 msec; 100 Hz; 20 sec). Venous samples were drawn over 30 sec 0.5 min before and 1.5 min after stimulation. Equal volumes of warmed isoncotic dextran were infused during sampling to prevent hypovolemia. ACTH was assayed by RIA. Areas were defined in which stimulation led to increased, decreased,, or unchanged ACTH. Mean changes in ACTH were tested by analysis of variance. The present data indicate that the ACTH-active areas defined previously in the midbrain may join the medial forebrain bundle in the subthalamic area and nucleus to traverse the lateral hypothalamus. At the level of the mammillary bodies, a facilitatory area occupied the ventral portion of the medial forebrain bundle. This area extended rostrally and medially to join the medial aspect of the medial forebrain bundle. Continuity with the mediobasal hypothalamus was seen only anteriorly in the area of the supraoptic decussations. An inhibitory area occupied the dorsal extent of the medial forebrain bundle at the level of the mammillary bodies. It extended rostrally and laterally around the caudal pole of the supraoptic nucleus and then medially at the level of the optic chiasm. There appear to be no other medial projections of the lateral lying ACTH-active areas to the mediobasal hypothalamus. The lateral hypothalamus may serve as a site of passage and/or of processing of information that ascends from the midbrain and descends from the limbic system. PMID- 6250802 TI - 3,5,3'-triiodothyronine receptor-containing chromatin fragments: production by nuclease digestion. AB - Nuclear thyroid hormone (T3) receptors are nonhistone proteins which are tightly bound to rat liver chromatin. The solubilization of the T3 receptors by micrococcal nuclease was studied using an assay which allows the delection of in vitro hormone binding and which is independent of the state of solubility of the chromatin. Nuclease digestion produces a receptor containing moiety which sediments at a rate of 5--6S. This form of the receptor is different than that released from chromatin at high ionic strength (3.8S) and potentially represents the stable association of the receptor which other elements of chromatin. Partial release of chromatin compaction by the use of dilute buffer solutions increases the rate of nuclease digestion, facilitates the release of the (5--6S) T3 receptor complex, and allows the isolation of sucrose gradient fractions which are enriched with receptor. PMID- 6250804 TI - The metabolism of estriol-3-glucosiduronate and estriol in the rabbit. AB - Urinary metabolites of [6,7-3H]-estriol-3-glucosiduronate and of [6, 7-3H] estriol in intact female rabbits were analyzed. The separation of urinary metabolites was performed by countercurrent distribution followed by DEAE Sephadex A-25 column chromatography. Each conjugate was then hydrolyzed with the enzymes and the aglycone thus liberated was identified. In either case, major urinary metabolites were found to be diconjugates, a considerable part of which was glucosiduronate-N-acetylglucosaminide of 17-epiestriol. In addition, estriol 16-glucosiduronate or monoglucosiduronate of 17-epiestriol was identified as a minor urinary metabolite of [6,7-3H]-estriol. From these results, it was concluded that the greater part of the estriol-3-glucosiduronate was converted to diconjugates and that estriol-3-glucosiduronate was probably an intermediate metabolite in the conversion pathway from estriol to diconjugates in this species. PMID- 6250803 TI - High-fiber diet in the control of diabetes in rats. AB - The effects of high-fiber diet on the metabolic states in streptozotocin-induced diabetic rats were investigated. The animals were divided into three groups: group A fed on a diet containing 5% of fiber (bagasse), group B paired-fed on a control diet and group C fed on a control diet ad libitum. The body weight gain was greater and the fasting blood sugar level was lower in A than B and C. The plasma triglyceride level was lowest in A, while no significant difference in the serum total cholesterol level was observed between A and B. Plasma glucagon levels were decreased in A and increased significantly in B and C. Plasma insulin levels were not changed in these groups. These results support the theory that a high-fiber diet is an effective therapeutic regimen for the control of metabolic derangement in diabetics. PMID- 6250805 TI - In vitro examination of LH-HCG receptors in human corpora lutea of the menstrual cycle and pregnancy. AB - Binding of 125I-human chorionic gonadotropin (HCG) to homogenates of the human corpora lutea of the menstrual cycle and pregnancy was examined in vitro. While corpora lutea of the menstrual cycle bound 125I-HCG specifically, the corpora lutea of pregnancy from 8 weeks' gestation bound little or none of the added 125I HCG. In the corpus luteum of the menstrual cycle the dissociation constant for HCG and the number of binding sites were analyzed by a Scatchard plot. However, from these observations along with the findings of earlier reports, it may be suggested that LH-HCG receptors remain reduced in number in the corpus luteum of pregnancy. PMID- 6250806 TI - A case of oat cell carcinoma of the lung associated with ectopic production of ADH, neurophysin and ACTH. AB - A woman with oat cell carcinoma of the lung showed the typical findings of the syndrome of inappropriate secretion of ADH initially during her hospital course. Ectopic production of ADH was indicated. The presence of ectopic production of ACTH was then suggested after the appearance of the elevation of plasma cortisol and ACTH which was not suppressed by dexamethasone administration. The laboratory findings of metabolic alkalosis and hypokalemia were also consistent with hyperadrenocorticism. In tumor tissue obtained by biopsy, ACTH and ADH were proven to be present by radioimmunoassay as well as nicotine-stimulated neurophysin and estrogen-stimulated-neurophysin. This was a rare case in which the simultaneous production of ADH and ACTH was clinically diagnosed. It is suggested that the elevation of neurophysins in plasma is of value in the diagnosis of ectopic production of ADH. PMID- 6250807 TI - Experimental models for study of common respiratory viruses. AB - Numerous epidemiological studies have shown that there is excess respiratory disease morbidity in areas of high atmospheric pollution, implying an interactive effect on the clinical illness associated with these common infections. The principal etiologic agents of human respiratory infections are respiratory syncytial virus (RSV), influenza viruses (IV), parainfluenza virus types 1 and 3 (P1, P3), adenoviruses (AD), rhinoviruses (RV) and Mycoplasma pneumoniae (Mpn). Understanding the pathogenesis of the excess morbidity related to pollutants would facilitate detection of undesirable human health effects and provide a basis for intervention strategies. Through use of experimental model systems the mechanism of toxic effects could be defined (whether microbiological, immunological, pathological or physiological) to provide direction for appropriate studies in the human host. Small animal models of IV and Mpn infections have been available for many years; recently, experimental models of several more common viral diseases have been developed. A parallel to human RSV infections is provided by the ferret: virus replicates in the lungs of infant animals, but only in the noses of adults. The common cotton rat infected with RSV develops small airways lesions which may mimic the pathophysiologic changes of bronchiolitis. Both guinea pigs and Syrian hamsters are susceptible to human P3 virus, developing peribronchiolar and interstitial lesions. Practical small animal models for human AD and RV infections are not available because of the high host-specificity of these agents. Both the RSV and P3 model infections are nonlethal which enables study for long-term sequelae. Recent reports of pulmonary function abnormalities among children suffering bronchiolitis in infancy underscores the importance of defining toxic influences which could play a role by making the initial infections more severe. PMID- 6250808 TI - Chemical modulation of alveolar epithelial permeability. AB - The volume and composition of fluid on the surface of the alveoli can affect alveolar ventilation, gas diffusion, and macrophage function. The passive permeability and active processes of the alveolar epithelial lining play a role in regulating surface fluid and are a potential site of damage by airborne chemicals. Like other epithelial barriers, the alveolar lining is permeable to lipophilic substances but restricts the transmural flow of small ions and hydrophilic nonelectrolytes (equivalent pore radius ca. 0.5-1.5 nm). The mammalian fetal lung and alveolar sacs of the adult bullfrog secrete Cl- and K+ into the airspace. Secretion by the fetal lung ceases at birth. Many environmental agents increase the permeability of the capillary endothelium and/or respiratory epithelium and induce pulmonary edema. Studies with bullfrog alveolar sacs have demonstrated that selective effects may or may not be followed by general derangement of the epithelial barrier. Exposure of the luminal surface to HgCl2 (10(-6) to 10(-4) M) induces a selective increase in Cl- secretion that is followed by a fall in transport and a general increase in ion permeation. CdCl2 (10(-5) to 10(-3) M) depresses ciliomotion on cells on the trabecula of the alveolus but does not affect Cl- secretion or transepithelial conductance. HNO3, like other mineral acids, increases conductance and the radii or pores in the barrier, whereas NaNO3 selectively inhibits Cl- secretion. Amphotericin B(10(7) to 10(-5) MJ) induces K+ secretion into the lumen of both bullfrog and rat lung. We conclude that environmental agents induce changes in epithelial function that may compromise the lung's ability to regulate respiratory fluid without destroying the characteristic permeability of the epithelial lining. PMID- 6250809 TI - Angiotensin-converting enzyme: I. New strategies for assay. AB - The disposition of converting enzyme (kininase II) on the luminal surface of pulmonary endothelial cells is well established. Further, it is known that there is a net conversion of angiotensin I into angiotensin II as blood passes through the lungs. However, little is known about modulations of converting enzyme activity that may arise through, e.g., changes in the quality of inhalants, blood flow, or blood oxygenation. There are few data on the effects of lung disease. A major barrier to studies to examine for pathophysiologic modulations of converting enzyme is that of assay. The enzyme can be measured in terms of the rate of formation of angiotensin II from a known quantity of angiotensin I. However, both peptides are biologically active, and lungs contain other enzymes capable of degrading them. We have developed a series of radiolabeled, acylated tripeptides to improve our ability to examine for changes in the net converting enzyme of intact lungs. The enzyme, a dipeptidyl carboxypeptidase, is capable of removing C-terminal dipeptides from a variety of oligopeptides. We have prepared benzoyl-Gly-Gly-Gly (I), benzoyl-Pro-Phe-Arg (II), benzoyl-Gly-His-Leu (III), benzoyl-Phe-Ala-Pro (IV), and benzoyl-Phe-His-Leu (V), each containing a (3)H atom in the para position of the benzoyl moiety. Substrates I and III have been used previously in photometric assays of low sensitivity. II is the acylated C terminal tripeptide of bradykinin, IV is an acylated tripeptide analog of BPP(5a) ( 11.5 producing the well known violet chromophores CuIIN4(-). In general these complexes, which also include the Cu(II) biguanides, show a clearly resolved electron paramagnetic resonance spectrum with nitrogen superhyperfine structure. 5. A third class of peptide model ligands (class C) consists of those amides where the CuII-X bond does not provide enough thermodynamic stability. The binding site of these class C amides includes functional groups such as carboxylate (COO-), methionine sulfur (RSR'), aliphatic or aromatic hydroxyl (OH) and amide nitrogen (NHCO) itself. When X is a pyridine (sp2) nitrogen or an amino (sp3) nitrogen, NHCO deprotonation is only promoted in five-membered but not six membered ring chelates. On the other hand, a combination of COO- and NH2, as in asparagine, will allow deprotonation of NHCO in the presence of Cu(II). And third, despite a pronounced unidentate affinity of the imidazole nitrogen for Cu(II), N-acetylhistamine acts as a class C amine, in contrast to imidazolylacetamide, which forms a stable Cu(II) peptide chelate. This difference in Cu binding is explained on the basis of space-filling models. These clearly demonstrate that in the case of the 2:1 complex of Cu(II) with N-acetylhistamine, the planarity of the ionised peptide function can not be retained in a square planar arrangement of the two amide ligands around the copper center. PMID- 6250849 TI - Catecholamines and cyclic AMP in allergic and exercise induced asthma of childhood. PMID- 6250851 TI - Lack of evidence for non-virion cell surface antigens on virally-induced murine mammary tumor cell. PMID- 6250850 TI - Achondrogenesis type I: light and electron-microscopic studies. AB - The light- and electron-microscopic structure of articular and costal cartilage in a case of achondrogenesis type I has been described. The most characteristic ultrastructural change in the chondrocytes was conspicuous dilatation of the rough endoplasmatic reticulum (RER) which contained amorphous electronopaque material. This change in the RER was accompanied by marked hypertrophy of the Golgi apparatus; the matrix was basically unchanged. PMID- 6250852 TI - Lymphomas in C3H mice perinatally inoculated with (C3H X T6) F1 or C3H spleen cells. PMID- 6250853 TI - Cerebrospinal fluid ACTH and calcitonin in patients with CNS metastases from small cell bronchogenic carcinoma. PMID- 6250855 TI - Indomethacin-sensitive suppressor cells regulate the cell-mediated cytotoxic response to SV 40-induced tumor-associated antigens in mice. PMID- 6250854 TI - Macrophage requirement for in vitro generation of specific, secondary cell mediated cytotoxicity against SV 40-induced tumor-associated antigens in mice. AB - The role of adherent phagocytic cells in an in vitro secondary cytotoxic response against Simian virus 40 (SV 40)-induced tumor-associated antigens was investigated. Spleen cells (responder cells), from mice primed with syngeneic SV 40-transformed cells, extensively depleted of macrophages by filtration through a Sephadex G-10 column followed by iron carbonyl treatment, had a markedly decreased capacity to generate in vitro secondary cytotoxic reactivity against syngeneic SV 40-transformed cells when cultured with the relevant stimulator cells. The secondary response was restored by the addition of adherent peritoneal cells from normal mice syngeneic to those immunized with the antigen. Within a certain dose range, small numbers of peritoneal cells completely reconstituted the response, whereas large numbers inhibited the reactivity. The restored cultures maintained specific cytotoxic reactivity against SV 40-induced tumor associated antigens which was mediated by effector T cells as shown by sensitivity to anti-Thy-1.2 antiserum and complement. These results suggested a requirement for adherent phagocytic cells (accessory cells) in in vitro generation of a secondary, cytotoxic response to tumor-associated antigens. PMID- 6250856 TI - T cell-mediated cytotoxic immune responsiveness of chimeric mice bearing a thymus graft fully allogeneic to the graft of lymphoid stem cells. AB - Fully allogeneic, chimeric mice were established by adult thymectomy of (A x B) F1 animals, grafting parental A-type thymus under the kidney capsula, followed by lethal (900 rd) irradiation and reconstitution with B parental-type bone marrow cells treated with xenogeneic anti-T cell antiserum plus complement. Following in vivo sensitization with inactivated Sendai virus (SV) suspensions, no virus specific T cells could be detected within the spleen cells of the mice. Upon stimulation with third-party allogenic cells in a primary mixed lymphocyte culture, spleen cells of all animals generated alloreactive cytotoxic T lymphocytes (CLT). More interestingly, upon secondary in vitro stimulation with inactivated SV-conjugated B-type stimulator cells, B-type-restricted, virus specific CTL were inducible in each case. Upon restimulation with SV-conjugated A type stimulator cells, A being the H-2 type of the grafted thymus, T cells of some but no all mice generated A-type-restricted, virus-specific CTL. The data suggest that in allogeneic, chimeric mice virus-specific CTL can be induced. Moreover, virus-specific CTL, restricted to the H-2 type of the lymphoid stem cell inoculum, are more readily inducible than those restricted to the H-2 type of the allogeneic thymus. PMID- 6250857 TI - Investigation into different types of post- and presynaptic alpha-adrenoceptors at cardiovascular sites in rats. PMID- 6250858 TI - Prazosin increases paradoxical sheep. AB - Prazosin 0.5 and 1.0 mg/kg i.p. induced a prompt and enduring increase in paradoxical sleep in the cat. The maximal effect, 140 percent above control was observed during the first 4 h after 1 mg/kg. In 16 h polygraphic records the respective increment was 69%. After 10 mg/kg paradoxical sleep was inhibited but it returned to control levels in 16 h. These results are discussed with reference to our previous experiments with agents having different alpha 1- and alpha 2 antagonist or agonist potency. It is concluded that selective, moderate blockade of alpha 1-receptors favours paradoxical sleep. PMID- 6250859 TI - Adenosine antagonizes the positive inotropic action mediated via beta-, but not alpha-adrenoceptors in the rabbit papillary muscle. AB - In the isolated rabbit papillary muscle, adenosine (1-300 microM) alone scarcely affected the basal tension developed. The positive inotropic action of isoprenaline, mediated via beta-adrenoceptors, was inhibited by adenosine in a concentration-dependent manner. Atropine (0.3 microM) abolish the inhibitory action of carbachol on the isoprenaline-induced positive inotropic action but not affect the inhibitory asction of adenosine. Adenosine failed to inhibit the positive inotropic action exerted by phenylephrine via stimulation of alpha adrenoceptors in the presence of pindolol (30 nM). The present results indicate that the positive inotropic action was mediated via alpha-adrenoceptors whose subecllular mechanism was not susceptible to the inhibitory action of adenosine as are beta-adrenoceptors. PMID- 6250860 TI - Naloxone promotes stimulus-evoked vasopressin release in vivo. PMID- 6250861 TI - Effects of cholecystokinin-like peptides on rearing activity and hexobarbital induced sleep. AB - Caerulein and the C-terminal octapeptide of cholecystokinin (CCK-8), when subcutaneously injected into mice, inhibited spontaneous rearing activity and prolonged the hexobarbotal sleeping time. These effects were resistant to naloxone. In molar terms, caerulein was 40 times (hexobarbital potentiation) or 115 times (rearing) more potent than diazepam. CCK-8 was less active than caerulein) though still superior to diazepam. PMID- 6250862 TI - Oestrogen and progesterone change the binding characteristics of alpha-adrenergic and serotonin receptors on rabbit platelets. AB - The binding characteristics of the alpha-adrenergic and serotonin receptors on intact rabbit platelets were identified using [3H]-dihydroergocryptine and [3H]-5 hydroxytryptamine respectively. In untreated female rabbits a single slpha adrenoceptor and two serotonin receptors were identified with ligand affinities similar to those in human platelets. The effects of oestrogen and/or progesterone on the alpha-adrenergic and serotonin receptors of rabbit platelets were studied. Oestrogen alone increased the capacity of serotonin receptors but reduced that of the alpha-adrenoceptor. Oestrogen plus progesterone reduced the capacity of both receptors and reduced the affinity of the alpha-adrenoceptor. The possible mechanisms of the steroid-induced changes and the implications of these with regard to the effects of the oral contraceptive pill are discussed. PMID- 6250863 TI - Halothane effect on cAMP generation and hydrolysis in rat brain. AB - The volatile anesthetic halothane increased the rate of cAMP generation and decreased the rate of cAMP hydrolysis in rat cerebral cortex and cerebellum. The effect of halothane on the enzymes was reflected in a two-fold rise in cAMP content of cerebral cortical tissue exposed to the anesthetic at 3 vol% for 15 and 30 min. The action of halothane on adenylate cyclase is calcium-independent and different from the action of guanine nucleotides, sodium fluoride and specific transmitters. The Vmax of the enzyme is higher in the presence of the anesthetic. It is suggested that halothane, through conformational changes of the enzyme, renders more catalytic sites operative. PMID- 6250864 TI - The effect of histamine on cyclic AMP levels in guinea-pig tracheal smooth muscle. AB - Histamine (10(-5)--3 x 10(-4) M) increased the cylic AMP content of guinea-pig tracheal smooth muscle, the maximal effect being a 3-fold increase after 2-min incubation with 10(-4) histamine. Histamine-induced accumulation of cyclic AMP was not affected by propranolol or atropine, but was reduced by mepyramine. Aspirin and indomethacin abolished the cyclic AMP response to histamine and potentiated histamine-induced contractions of the smooth muscle. These results suggest that the elevation of cyclic AMP levels in response to histamine is mediated by prostaglandins, and represents an important negative feedback regulatory mechanism which modulates the contractile response of guinea-pig tracheal smooth muscle to histamine. PMID- 6250865 TI - Modification of the surface ATPase activity in cultured hepatoma cells by lipid depleted media. PMID- 6250866 TI - Alterations of cAMP metabolism and hormone responsiveness of cloned differentiated rat liver cells (RL-PR-C) upon spontaneous transformation. PMID- 6250867 TI - Polyethylene glycol- and lysolecithin-induced cell fusion between follicle cell and very small oocyte in Xenopus laevis. PMID- 6250868 TI - Multiple interconvertible forms of cAMP phosphodiesterase in normal, malignant and hybrid mammalian cells. PMID- 6250869 TI - Immunofluorescence radioautography. Simultaneous visualization of DNA replication and supramolecular antigens in individual cells. PMID- 6250870 TI - Effects of animal age and phenobarbital on rat liver glucose-6-phosphatase activity. PMID- 6250871 TI - AKR murine leukemia viruses and long-term bone marrow cultures from AKR and SJL mice. AB - We have evaluated the effects of AKR mouse retroviruses on a system of long-term bone marrow cultures which allows prolonged replication of hemopoietic stem cells (CFUs) and granulocyte-monocyte progenitors with production of mature granulocytes. Ecotropic-nononcogenic virus is expressed in all cultures and does not adversely effect stem cell replication. We found, however, that cultures established from mice treated in vivo with lymphomagenic AKR viruses (Gross murine leukemia virus and AKR SL3 murine leukemia virus) showed a more rapid decline in CFUs and CFUc than cultures from "normal" AKR mice. Only the former cultures were found to produce lymphomagenic viruses. Furthermore, it was shown that addition of lymphomagenic virus to three-week marrow cultures established from AKR and SJL mice also caused a prompt decline in progenitor cell production and granulopoiesis when compared to medium-treated control cultures. The fate of all cultures was a loss of CFUc and granulocytes with a continuous production of macrophages. The change to macrophage production occurred earlier in the cultures treated with lymphomagenic virus or in those derived from lymphomagenic virus treated animals. A study of these bone marrow-drived macrophage cultures, as well as cultures of similar morphology but of thymic origin, showed that they could be maintained as continuous lines. Cells from three of the cultures from lymphomagenic virus-treated animals plroduced locally growing sarcoma when inoculated into mice. The macrophages from the declined marrow cultures differed in certain properties from those of the established lines. PMID- 6250872 TI - Cholinergic facilitation of thalamic relay transmission in the cat. PMID- 6250873 TI - Glucocorticoid modification of the responsiveness of a fast (type 2) neuromuscular system to edrophonium and d-tubocurarine. PMID- 6250874 TI - Boophilus microplus: cattle antienzymes to larval phosphomonoesterases. PMID- 6250875 TI - The prevention of rehospitalization of adolescents and young adults. AB - This paper presents a family-oriented therapy approach for the prevention of rehospitalization of adolescents and young adults with diverse diagnoses. The dilemma of the family is presented in terms of the incongruities evident in the organizational hierarchy of these families. The main premise is that if the hierarchy is corrected so that the parents are jointly in charge of the youth and the extended kin cooperate, rehospitalization can be prevented. A therapeutic strategy is presented with the emphasis on overcoming the family's attempt to avoid a hierarchy in which the parents are in charge of the family. PMID- 6250876 TI - [Basic electron optical characteristics of estrogens]. PMID- 6250877 TI - On the presence of poly(ADP-ribose) polymerase activity in metaphase chromosomes from HeLa S3 cells. PMID- 6250878 TI - Irreversible stimulation of Xenopus melanophores by photoaffinity labelling with p-azidophenylalanine13-alpha-melanotropin. PMID- 6250879 TI - Spectroscopic aspects of copper binding site in bovine serum amine oxidase. PMID- 6250880 TI - Heterogeneity and subcellular localization of hamster adipocyte alpha-adrenergic receptors: evidence of alpha 1- and alpha 2-subtypes. PMID- 6250881 TI - Protein phosphorylation in rat liver plasma membranes: in vitro and in vivo inhibition by insulin. PMID- 6250882 TI - Methjylation in Physarum DNA. PMID- 6250883 TI - Light activation of bovine rod phosphodiesterase by non-physiological visual pigments. PMID- 6250884 TI - Redox reactions in mixed-valence cytochrome c oxidase. PMID- 6250885 TI - The structural flexibility of ferric cytochrome c: regulation of the spin-state equilibrium by an anti-arthritic gold(I) compound at neutral pH. PMID- 6250886 TI - Hypothalamic peptides influencing secretion of ACTH by isolated adenohypophysial cells; two corticotrophin releasing factors and a potentiator. PMID- 6250887 TI - Basement membrane glycoprotein laminin binds to heparin. PMID- 6250888 TI - Asymmetric transcription of cauliflower mosaic virus genome by the Escherichia coli RNA polymerase in vitro. PMID- 6250889 TI - Regulation of liver phosphorylase phosphatase: ATP-Mg-mediated activation of the partially purified dog-liver enzyme. PMID- 6250890 TI - Effect of methylamine on internalization, processing and biological activation of epidermal growth factor receptor. PMID- 6250891 TI - The effect of methylglyoxal on the glycolytic enzymes. PMID- 6250892 TI - The P-light chain of rabbit skeletal muscle myosin: a 31P NMR study. PMID- 6250893 TI - In vitro inactivation of oestrogen receptor by nuclei: prevention by phosphatase inhibitors. PMID- 6250894 TI - Sequence of the 3'-terminal portion of Drosophila melanogaster 18 S rRNA and of the adjoining spacer: comparison with corresponding prokaryotic and eukaryotic sequences. PMID- 6250895 TI - Two sequence-specific deoxyribonucleases from Rhodospirillum rubrum. PMID- 6250896 TI - Calcium binding properties of the C1 subcomponents C1q, C1r and C1s. PMID- 6250897 TI - An essential sulfhydryl group at the substrate site of the fumarate reductase of Vibrio succinogenes. PMID- 6250898 TI - Chemical radiolabeling of carboxyatractyloside by [14C]acetic anhydride: binding properties of [14C]acetylcarboxyatractyloside to the mitochondrial ADP/ATP carrier. PMID- 6250899 TI - Na+ transport via Na+/H+ antiport in Halobacterium halobium envelope vesicles. AB - Using H. halobium cell envelope vesicles containing either bacteriorhodopsin plus Na+ pump, bacteriorhodopsin alone, Na+ pump alone, or no light-responsive pigment altogether, it could be shown that the large majority of light energized Na+ extrusion in these mutants is linked to bacteriorhodopsin and to protonmotive force, and therefore must be facilitated by a Na+/H+ antiporter. Thus, the recently discovered primary Na+ pump makes only a minor contribution to light mediated Na+ flux. The activity of the Na+/H+ antiporter appears to be independent of the presence of any photoreactive pigments, since an artifical electron donor will drive rapid Na+ extrusion in all of the vesicle preparations tested. PMID- 6250900 TI - Sodium/proton antiporter of rat liver mitochondria. PMID- 6250901 TI - A novel type of superoxide generating system in nuclear membranes from hepatoma 22a ascites cells. PMID- 6250902 TI - Identification of mitochondrial DNA species in interspecific cybrids and reconstituted cells using restriction endonuclease. PMID- 6250903 TI - Biochemical evidence for intertypic genetic recombination of polioviruses. PMID- 6250905 TI - Insulin controls the cyclic AMP-dependent phosphorylation of integral and peripheral proteins associated with the rat liver plasma membrane. PMID- 6250904 TI - Does caeruloplasmin dismute superoxide? No. PMID- 6250906 TI - The influence of glycosidases and lectins on insulin binding to Zajdela hepatoma cells. PMID- 6250907 TI - A new site-specific endonuclease from Neisseria cinerea. PMID- 6250908 TI - Nitroguanidyl-lutropin, a derivative which inhibits the stimulation of ovarian adenylate cyclase by lutropin. PMID- 6250909 TI - The formation of the primary compound from hydrogen peroxide and Pseudomonas cytochrome c peroxidase. PMID- 6250910 TI - Recent progress in vitamin D metabolism and the chemistry of vitamin D metabolites. PMID- 6250911 TI - Symposium. Probes of cellular composition in epithelia. PMID- 6250912 TI - Pituitary hormones in the brain: what is their function? AB - Data concerning the presence in the central nervous system of the anterior and intermediate lobe hormones ACTH, beta-lipotropin, alpha-melanocyte stimulating hormone, beta-endorphin, prolactin, growth hormone, gonadotrophic hormone, and thyrotropin stimulating hormone are reviewed. Available evidence for the ACTH lipotropin family of peptides indicates that synthesis can occur in brain as well as in pituitary. Although behavioral effects have been described for some of these peptides and their fragments (ACTH, alpha-MSH, beta-endorphin, prolactin), the physiological relevance and the mechanisms of such effects, the nature of the biosynthetic pathways involved, and the factors regulating the brain concentrations of these peptides remain to be explored. PMID- 6250913 TI - [Aerosil stabilization of drug mixtures]. PMID- 6250914 TI - Sperm motility. PMID- 6250915 TI - [Cholinergic sympathetic influences on blood flow and cyclic nucleotide concentration in skeletal muscles]. AB - The content of 3.5 cGMP increased twofold and the content of 3.5 cAMP remained unchanged in the cat skeletal muscle during vasodilatation evoked by hypothlalamic stimulation. Cholinergic vasodilatation increased also phosphorylase activity by 90%. These effects were blocked by atropine. Possible existence of an interrelationship among the vasodilator effect, phosphorylase activity and increase in cGMP, is discussed. PMID- 6250916 TI - [Structuro-functional organization of the vegetative (autonomic) nervous system]. AB - On the basis of a number of structural and functional indices, application of pharmacological analysis as well as recording of neuronal activity, the autonomic nervous system is subdivided into the sympathetic, parasympathetic and metasympathetic parts. The metasympathetic system includes the complex of microganglia situated in the walls of vosceral organs and having marked motility activity (the heart, ureters, intestine, stomach). According to the localization, separate areas of this system can be defined by its site (for example, the cardiometasympathetic area in the heart). The metasympathetic system attains the features of true autonomy. Its cells have no direct connection with the high centers: this connection is established through mono- and polysynaptic sensory and afferent units of sympathetic and parasympathetic nature. The system has a definite set of functional elements including sensory ones (mechano-, chemo- and thermosensitive those), oscillators, interneurons, tonic neurons. Neurons of the metasympathetic system are incorporated through interganglionic connections into the common functional network of the organ. A typical excitatory pattern suggests the presence of a temorary connection in the work of at least two neurons according to the "driver--follower" type. In addition to excitatory patterns there are also patterns showing inhibitory interactions. Besides well known systems of mediation including cholinergic and adrenergic ones, the metasympathetic system has its peculiar purinergic transmission. PMID- 6250917 TI - [Electrophysiologic analysis of mediator stores and release in smooth muscle synapses of the nictitating membrane in cats]. AB - At the adrenergic junction of the sympathetic nerve with the medial smooth muscle of the cat nictitating membrane, blocking of the reuptake of noradrenaline with phenoxibenzamine suppressed the amplitude of rhythmic excitatory synaptic potentials. Stimulation of postganglionic sympathetic nerve (10/sec) made the time constant of the first component of the potential 60 sec whereas that of the second component--600 sec. The depression of amplitude seems to be connected with possible decrease in the noradrenaline release and partial exhaustion of its storage. The analysis of the transmitter function showed the release of noradrenaline to a single impulse to be in the reverse relation to the stimulation frequency and at 10/sec to constitute about 3 x 10(-4) (at 20/sec 1.9 X 10(-4)) of the transmitter storage. The replenishment of the transmitter (4 x 10(-6) of the initial operating pool of noradrenaline to a single impulse at 10/sec) was intensified parallel to the increased frequency of adrenergic neurons firing and was able to provide for afferent synaptic transmission within the working frequencies of the afferent part of the sympathetic reflex arch. PMID- 6250918 TI - [Conduction pathways of the caudal mesenteric sympathetic ganglion in guinea pigs]. AB - Stimulation of the intermesenteric tract induced a biphasic response in left and right colonic nerves. In splanchnic nerves, the response had three peaks two of them being conducted by fibers passing through the ganglia. The third component disappeared at 30--40/sec stimulation and in antidromic stimulation. The projections from limbar splanchnic nerves to postganlionic trunks were characterized by one more stable potential with great latency due, probably to interneurons. A scheme of the ganglion pathways has been composed. PMID- 6250919 TI - Detection of viral markers and incomplete viral genome rescue from ASV transformed rodent cells. AB - Two non-virogenic rat cell lines TWERC and FR transformed with PR-RSV and FSV, respectively, were analyzed. Both these cell lines contained vRNA, but only in TWERC cells was the major viral polypeptide p27 synthetized. Transforming virus can be rescued from both cell lines only after fusing them with chicken fibroblasts preinfected with avian leukosis viruses of subgroup A, C, D, F and both td mutants of PR-RSV-C and B77-C. Similarly, virus was rescued in experiments in which QEF infected with RAV-1 or DEF infected with td B77-C or RAV 61 were employed as indicator cells. On the contrary, DEF infected with MuLV-X and probably also myeloblasts transformed with AMV were not active in virus rescue. No virus rescue was observed in long-term passaged non-virogenic mouse cell lines RVP(3) and RVA(4), using the same spectrum of helper virus-infected avian cells, which gave positive virus rescue with the non-virogenic rat cells. In both mouse cell lines, also no vRNA or p27 was detected. In 13 independent experiments in which TWERC cells were fused with RAV-1-infected BLEF, rescued viruses were isolated. Using two independent host-range tests, only the subgroup A specificity was detected in the viral isolates tested, which is the subgroup of RAV-1 used as a helper virus. These and other experiments indicate that ASV rescued from TWERC cells acquire in a vast majority of cases the env gene product only from the helper virus which suggests that the viral genome(s) present in TWERC cells is (are) vastly deficient in the env gene. The specificity of helper virus and indicator cells both required for the virus induction from some nonvirogenic cells and the possibility of the loss of viral genome from other non virogenic cell lines are discussed. PMID- 6250920 TI - [Urinary cyclic AMP and nephrogenous cyclic AMP in the diagnosis of parathyroid disorders (author's transl)]. PMID- 6250921 TI - [2 cases of congenital adrenocortical unresponsiveness to ACTH (author's transl)]. AB - Congenital adrenocortical unresponsiveness to ACTH is characterized by hyperpigmentation, muscular weakness, and episodes of hypoglycemia, with lethargy or coma and convulsion, and without signs or symptoms of salt wasting. Endocrinological evaluation reveals low levels of serum and urinary glucocorticoids, elevated levels of plasma ACTH and unresponsiveness to exogenous ACTH. On the other hand, aldosterone secretion or excretion is normal and is elevated during a low sodium diet. We reported on two patients with this syndrome. Case A, a 4 year-old-girl, showed skin hyperpigmentation, hypoglycemia, convulsion and coma. She was tall wlth a marked advance of bone age. Case B, a 4 year-old-boy, showed skin hyperpigmentation, fatigability and muscular weakness. Both of them revealed low urinary excretion of THE, THF, cortolone, and beta cortolone and low levels of plasma cortisol. The levels of urinary glucocorticoids and plasma cortisol did not respond to ACTH administration. During a low sodium diet, urinary aldosterone excretion was elevated, urinary sodium excretion ws decreased, and the patients were able to conserve sodium normally. We also summerized other reported cases and discussed the etiology of this syndrome. PMID- 6250923 TI - [On the encapsulated intraneural granular cell tumor (author's transl)]. AB - Two cutaneously and subcutaneously localized nodules of the left mamma from a 66 year-old patient were excised. The lesions were flesh-colored, firm and well circumscribed. Sections of the tumors show the typical aspects of granular cell tumor. The lesions were both surrounded by a condensation of fibrous tissue which formed a capsule. This condensaton of fibrous tissue resembled and on some sections was in continuity with the perineurium of a nerve. In addition to that is the finding of granular cells situated within a nerve fascicle and apparently replacing several, or all, of the nerve fibres. PMID- 6250924 TI - Induction of antibody tolerance to sheep erythrocytes in lizards using modified erythrocyte preparations. PMID- 6250922 TI - A serological study of herpes simplex virus type 1 antibody over a 13-year period. AB - HSV-1 serum antibody titers determined by 50% plaque reduction and confirmed by radioimmunoassay in 11 samples from an individual over a 13-year period indicated a significant increase between the first sample and a sample taken 9 years later. This increase did not seem to reflect loss of antibody in the low titered serum sample due to storage. PMID- 6250925 TI - Cell-mediated immune reponses to fungal, bacterial, viral, and chemical antigens in three nonhuman primate species. PMID- 6250926 TI - Rapid isolation of functionally intact pancreatic islets from mice and rats by percollTM gradient centrifucation. AB - A discontinuous gradient of Percoll was used to effectively separate islets of Langerhans from collagenase digested pancreas from mice and rats. Percoll isolated islets and islets isolated by direct hand-picking from the pancreatic digest were maintained in tissue culture. Percoll isolation of islets did not affect glucose-stimulated insulin release from islets cultured for one week nor the ability of islets from newborn rats to incorporate 3H-thymidine into DNA. Centrifugation in Percoll is an efficient method to isolate functionally intact pancreatic islets. PMID- 6250927 TI - Induction of syncytia by simian sarcoma virus type I (SSV-I/SSAV-I) in several human transformed cell lines. AB - Simian sarcoma virus type I (SSV-I/SSAV-I) induced syncytia formation in human cells derived from malignant tumors (KB, HEp-2 and HeLa cells) and human cells transformed by tumor viruses (RSa, RSb and KC cells) as well as rat XC cells. However, SSV-I/SSAV-I did not induce syncytia formation in human cells derived from normal embryos (WI-38, HEL and HEC). Syncytia-inducing activity of SSV I/SSAV-I was neutralized by anti-SSV-I/SSAV-I serum, indicating that syncytia formation was SSV-I/SSAV-I mediated. PMID- 6250928 TI - A comparative crossover study on the treatment of heartburn and epigastric pain: Liquid Gaviscon and a magnesium--aluminium antacid gel. AB - Forty-four patients with symptoms of gastro-oesophageal reflux were randomly assigned in a crossover trial to treatment for 15-day periods with Liquid Gaviscon (a reflux suppressant) or an antacid gel containing magnesium and aluminium hydroxide. Good relief of symptoms was reported by 84% of patients during therapy with Liquid Gaviscon compared to only 23% during antacid therapy. Relief of symptoms was obtained within 15 minutes by 68% of patients during therapy with Liquid Gaviscon compared to only 9% during antacid treatment. The beneficial effect lasted for more than 4 hours in 75% of patients during treatment with Liquid Gaviscom compared to only 23% of patients obtaining long term relief during antacid therapy. PMID- 6250929 TI - Interactions of glucagon with isolated rat-liver cells. Fate and subcellular localization of cell-associated hormone. PMID- 6250930 TI - Calcium- and potassium-channel blockers interact with alpha-adrenoceptors. AB - The so-called calcium antagonist D-600 and agents that enhance the influx of calcium ions into nerve terminals during action potentials (4-aminopyridine, tetraethylammonium, guanidine) interact with alpha-adrenoceptors. The interaction was revealed by binding experiments in vitro with the alpha 2- and alpha 1 specific ligands [3H]clonidine and [3H]prazosin, resp. D-600 binds in a competitive manner to alpha 2- and alpha 1-adrenoceptors in rat-brain membranes. [3H]Prazosin was used to identify alpha 1-adrenoceptors in rat-heart-membrane fragments. D-600 inhibited the binding of the tritiated antagonist, in a manner similar to that seen in rat-brain membranes. 4-Aminopyridine, guanidine and tetraethylammonium blocked no-competitvely the binding of [3H]clonidine in brain membranes. There ws little or no effect of these agents on the binding of [3H]prazosin to alpha 1-adrenoceptors in rat heart or brain. The results indicate that D-600 binds to a region common to alpha 1- and alpha 2-adrenoceptors, whereas the potassium-channel blockers reveal a structural feature of the alpha 2 adrenoceptors in brain membranes which is also present in voltage-dependent potassium channels but is not shared by alpha 1-adrenoceptors. PMID- 6250931 TI - Ontogeny of somatomedin during development in the mouse. Serum concentrations, molecular forms, binding proteins, and tissue receptors. PMID- 6250932 TI - Apparent cerebral atrophy in patients on treatment with steroids. AB - The apparent loss of cerebral tissue sometimes demonstrated by computerised axial tomography and other radiological techniques is not always irreversible. A report is given of a child with infantile spasms who was treated with ACTH. While on this treatment, a CAT scan showed findings suggestive of cortical atrophy but when this test was repeated four months after treatment was stopped, it was normal. Various theories are discussed to account for the effects of steroids on the brain. The most likely one is a change in brain volume because of loss of water. As the radiological appearances can be reversible, they should not be described as cerebral atrophy. PMID- 6250933 TI - Gastric gastrinoma and diffuse G cell hyperplasia associated with chronic atrophic gastritis. Endoscopic detection and removal. AB - Chronic atrophic gastritis and a sessile polyp were diagnosed during gastroscopy of a patient with splenomegaly and portal hypertension. The polyp was removed endoscopically. Histologically, it proved to be an endocrine tumour, which was identified as gastrinoma by immunohistochemistry. Then, hypergastrinemia was found and gastrectomy was performed to ensure complete removal of the tumour. The surgical specimen showed G cell hyperplasia of the antro-pyloric mucosa and severe atrophic gastritis with scattered argyrophil micronodules in the corpus fundus region. 3 years after this treatment the patient is well. PMID- 6250934 TI - Biochemical and ultrastructural studies of cultured rat astroglial cells: effect of brain extract and dibutyryl cyclic AMP on glial fibrillary acidic protein and glial filaments. AB - The growth of astroglial cells in primary cultures derived from newborn rat cerebral hemispheres was investigated in the absence and in the presence of newborn rat brain extract or dBcAMP. The parameters chosen were the content of DNA, total protein, and glial fibrillary acidic protein (GFA) as well as the morphologic development of gliofilaments. During the entire culture period the DNA content increased in control culture indicating a continuous cell division, whereas the cells stopped dividing after 14 or 4 days of treatment with either brain extract or dBcAMP respectively. In contrast, a constant increase of total protein was found in both control and treated cultures. Since cell divisions had stopped in treated cultures, the increase in total protein in these cultures indicates growth of the individual cells. The GFA levels increased progressively and similarly in control cultures and in cultures treated with brain extract. The values in the treated cultures remained slightly higher than those in controls. Conversely, immediately after the addition of dBcAMP a sudden increase in GFA protein occurred and the amounts were statistically significantly different from those of the controls. The GFA levels were expressed relative to total protein indicating that GFA constitutes an increasing amount of the total protein of the individual cells during culture. The changes in the amount of GFA was shown to parallel the morphologic development of gliofilaments. Indeed, when the level of GFA increased a progressive accumulation of gliofilaments was observed. The results obtained were discussed in relation to the astrocytic maturation. PMID- 6250935 TI - Central inhibition of basal pancreatic and gastric secretions by beta-endorphin in rats. AB - The effects of intracerebroventricular injections of synthetic ovine beta endorphin were tested in conscious rats with gastric and pancreatic fistulas. In the range of 0.8 to 25 microgram injected in the third ventricle of the brain, basal gastric and pancreatic secretions were strongly inhibited in a dose dependent manner. Pancreatic volume, bicarbonate output, and total protein output were similarly inhibited, while the bicarbonate concentration was only slightly changed. Similar effects were noted after the administration of morphine. In the present model system, morphine was 20-30 times less active than beta-endorphin on a molar basis. Beta-Endorphin inhibition of pancreatic secretion was reversed by naloxone, suggesting that opiate receptors are involved in this phenomenon. Gastric acid secretion participated in the pancreatic effects of beta-endorphin to only a slight extent, since pancreatic inhibition by the endorphin was decreased only slightly in rats with gastic fistula in which gastric juice was diverted and did not reach the duodenum. The comparison of intravenous and intraventricular injections of beta-endorphin and morphine suggested that the observed inhibitions originated in the central nervous system. No effects were detected after the administration of alpha-endorphin, Met-enkephalin or Leu enkephalin, although pancreatic secretion was measurably inhibited by long-acting synthetic enkephalin analogues. PMID- 6250936 TI - The use of Boot's secretin in the secretin stimulation test. PMID- 6250937 TI - [Carcinoembryogenic antigen (CEA) and lactoferrin (LF) in benign and malignant disease of the breast. A contribution to the immuno-histological demonstration of marker substances (author's transl)]. PMID- 6250938 TI - [Suppression of free plasma oestriol in high-risk pregnancies after stimulation of the maternal adrenals by ACTH (author's transl)]. PMID- 6250939 TI - Daily rhythms of liver cAMP, total liver lipids, prolactin-like hormone and growth hormone cell activities in Sarotherodon mossambicus acclimated to different photoperiod regimes. PMID- 6250940 TI - Effects of mammalian gonadotropins on progesterone release and cyclic nucleotide production by isolated avian granulosa cells. PMID- 6250942 TI - [Stimulation of the corticomelanotropic cells in the hypophyseal pars intermedia of the boxfish, Boops salpa L. (a marine teleost) subjected to acoustic neurogenic stress]. PMID- 6250941 TI - The presence of steroids in the sera of the Pacific hagfish, Eptatretus stouti, and the sea lamprey, Petromyzon marinus. PMID- 6250943 TI - Coexistence of alpha-melanocyte-stimulating hormone and adrenocorticotrophin in all cells containing either of the two hormones in the duck pituitary. PMID- 6250944 TI - The nucleotide sequence of adenovirus type 5 early region E1: the region between map positions 8.0 (HindIII site) and 11.8 (SmaI site). AB - The nucleotide sequence of the region between map positions 8.0 (HindIII site) and 11.8 (SmaI site) of adenovirus type 5 (Ad5) has been determined. Together with the sequences reported earlier (Van Ormondt et al., 1978; Maat and Van Ormondt, 1979) it encompasses the entire leftmost early region E1 of Ad5 DNA (4126 base pairs). The total sequence revealed a number of potential regulatory signals (promoter sites, ribosome binding sites, 3'-poly(A)-associated sequences), which confirm that region E1 is divided into subregions, E1a and E1b, and a region coding for semi-late viral protein IX. By taking into account the adenovirus 2 (Ad2) RNA-splicing data of Perricaudet et al. (1979; 1980) and the Ad2 RNA mapping data of Chow et al. (1979) we predict that E1a codes for polypeptides of 32, 26 and ca. 13 kd, and subregion E1b for polypeptides of 67 kd and 20 kd; the expected molecular weight of protein IX is 14.4 kd. PMID- 6250945 TI - Characterization of a site-specific restriction endonuclease SphI from Streptomyces phaeochromogenes. AB - A new type-II restriction endonuclease SphI, has been partially purified from Streptomyces phaeochromogenes. SphI recognizes the hexanucleotide sequence 5' GCATGC and cleaves it at the position marked by the arrow. This nucleotide sequence is present twice in SV40 DNA, four times lambda DNA and only once in the cloning vehicles pBR322, pBR325, pBR327 and pBR328. PMID- 6250946 TI - Construction of restriction enzyme fragment libraries containing DNA from human adenovirus types 2 and 5. AB - Restriction-fragment libraries containing adenovirus type 2 (Ad2) DNA have been constructed, using the pBR322 plasmid (Bolivar et al., 1977) as a vector. Clones have been isolated which contain all the HindIII fragments of Ad2 DNA except the terminal G- and K-fragments inserted into the HindIII cleavage site of the vector. All the 13 SmaI-fragments of Ad2 DNA were separately inserted into the PstI site of the pBR322 vector after addition of homopolymeric poly(dG) tails to the fragments and poly(dC) tails to the linearized plasmid. Two large fragments of adenovirus type 5 (AD5) DNA, located between map positions 17.0 and 59.5 and between map positions 59.5 and 97.3, respectively, were cloned using bacteriophage lambda as a vector. All clones, which are described in the present report, are available upon request. PMID- 6250947 TI - A versatile primer for DNA sequencing in the M13mp2 cloning system. AB - A primer for DNA sequencing by the chain-termination method in the M13mp2 cloning system was constructed and amplified. The primer was isolated as an EcoRI/AluI restriction fragment. After conversion of the AluI end into an EcoRI end the fragment was cloned in pBR325 from which it can be recovered by cleavage with EcoRI. The primer hybridizes to the single-stranded DNA of the mature M13mp2 phage next to the site of insertion thereby directing DNA synthesis along the inserted DNA. PMID- 6250948 TI - Base distribution in the coding and noncoding regions in the rDNA of Lytechinus variegatus. AB - The EcoRI restriction endonuclease cleaves rDNA repeat units of the sea urchin Lytechinus variegatus into four fragments. The G + C contents of all four cloned restriction fragments were determined by ispycnic analysis. Electron microscopic denaturation mapping of one of the fragments allowed alignment of the denaturation pattern with the restriction map and correlation with previously reported transcriptional data. From these results the base distribution in the spacer region and regions coding for rRNAs was derived. PMID- 6250949 TI - Restriction endonuclease BamHI cleaves bacteriophage Mu DNA within cistrons E and F. AB - We have cleaved phage Mu DNA with restriction endonucleases EcoRI and BamHI and have cloned three specific DNA fragments from the middle of the Mu genome into vector plasmid pBR322. By marker rescue experiments, we have determined that the two BamHI cleavage sites in Mu DNA occur within cistrons E and F. PMID- 6250950 TI - [Malignant trophoblastic disease: management and evolution]. PMID- 6250952 TI - [Role of silicon dioxide in the development of lung tumors induced in rats by intratracheal administration of benz(a)pyrene]. PMID- 6250951 TI - [Effect of collagenase on sclerosis in different types of pneumoconiosis]. PMID- 6250954 TI - [Fiber supplemented meals in insulin-dependent juvenile diabetics]. PMID- 6250953 TI - [Development of experimental silicosis from the chronic inhalation of a colloidal solution of silicic acid]. PMID- 6250955 TI - [Malignant fibrous histiocytoma]. PMID- 6250956 TI - [Prolactin determination in the early diagnosis of pituitary tumors]. PMID- 6250957 TI - [Catecholamine-antagonistic effects of propranolol and the mechanical function of ventricular myocardium]. AB - The catecholamine-propranolol antagonism was studied on guinea-pig papillary muscles. 1. A competition between propranolol and catecholamine, the latter subject to saturable elimination from the extracellular space, for a homogeneous populations of beta-adrenoceptors of the cellular surface does not suffice to explain the influence on the inotropic effects. 2. The antagonism was differentiated into a "surmountable" and an "unsurmountable" component by means of the stereospecific influence of propranolol on maximal catecholamine effects in regard to velocity of contraction and acceleration of relaxation. The "unsurmountable" component was explained by a competition for intracellular beta adrenoceptors, in addition to the competition at the beta-adrenoceptors of the cellular surface ("surmountable" component). PMID- 6250958 TI - [Influence of food browning on nutrition. IV. Effect on trypsin action on a synthetic substrate (author's transl)]. AB - The action of brown substances on trypsin inhibition was studied using casein and a synthetic substrate, alpha-N-benzoyl-DL-arginine-p-nitroaniline. It was found that brown substances inhibit trypsin action similarly on both substrates. Lineweaver-Burk plots revealed that the inhibition was of irreversible, noncompetitive type in either case. Inhibitory action of each fraction after Sephadex G-25 passage was found to be proportional to the degree of food browning or oxidation. PMID- 6250959 TI - [Experimental and clinical studies on enzymes of mitochondria in various liver diseases; with special reference to alcoholic liver disease (author's transl)]. AB - Mitochondrial enzymes in rat livers or intestines were investigated in experimental models with ethanol- or other hepatotoxic agent-induced liver injuries and extrahepatic cholestasis. In clinical experiment, activities of mitochondrial GOT (mGOT) and ornithine carbasmyl transferase (OCT) were examined in alcoholisms and patients with other various liver diseases. Results obtained are as follows; 1) The activities of OCT and mGOT were increased particularly at onset of acute hepatitis, in chronic active hepatitis and intrahepatic cholestasis, showing that mitochondria were injured strikingly in these diseases. The activities in alcoholics were not so great, however mGOT/total-GOT ratio was increased in level than in other diseases. 2) Changes in mitochondrial enzymes of rat liver treated with ethanol were too varied to catch the actual tendency in this pathologic state. 3) Administration of galactosamine, carbon tetrachloride, or alpha-naphthyl isothiocyanate (ANIT) caused a significant fall in activities of succinate cytochrome C reductase and OCT, along with increase in serum activity of OCT, indicating severe mitochondrial injury with these drugs. Extrahepatic cholestasis following bile duct ligation showed the same changes of mitochondrial enzymes in liver tissue and serum. 4) These data indicate that observation of activities of serum OCT, mGOT, along with mGOT/total-GOT ratio are useful for estimation of mitochondrial damage in extra- and intra-hepatic cholestasis, and acute or chronic active hepatitis. The changes in alcoholic fatty liver was not so subtle as compared with other liver diseases. 5) It is surmized that smooth endoplasmic reticulum was increased in content and pentose phosphate shunt was inhibited by chronic ethanol treatment, estimating from increased activities of NADH-ferricyanide reductase and gamma-glutamyl transpeptidase, and decreased activity of glucose-6-phosphate dehydrogenase. 6) The changes in hepatic enzymes with ethanol treatment were paralleled with those of intestinal ones, indicating that metabolic changes in intestine contribute someway in the formation of alcoholic fatty liver. 7) Chronic ethanol treatment induced lowered active transport in intestinal mucosa, which indicates inhibition in absorption of various nutrients by ethanol. PMID- 6250960 TI - Effect of somatomedin A and insulin on cyclic AMP generation in isolated rat hepatocytes. AB - Insulin and somatomedin A were shown to have inhibitory action on glucagon stimulated but not basal cyclic AMP production in isolated rat hepatocytes. The inhibition was dose-dependent and the potency per mol was about 100 fold higher for insulin than for somatomedin A. PMID- 6250961 TI - Effect of thyroxine on the hepatic glycogen and glucose-6-phosphatase activity of developing rats. AB - The influence of exogenous thyroxine was studied on the hepatic glycogen content and glucose-6-phosphatase activity of rats of different age groups. The glycogen content and glucose-6-phosphatase activity were found to be decreased in the livers of 5, 15, 30 and 60-day-old rats after thyroxine treatment. In normal rats of 5, 15, 30 and 60-day-old, a gradual rise in both the hepatic glycogen content and glucose-6-phosphatase activity was noted as the age advanced from immature to adult. PMID- 6250962 TI - Involvement of adrenergic receptors in skeletal muscle metabolism of the cold adapted rat. AB - Hind-limb perfusion was used to investigate alterations of alpha and beta receptor-mediated metabolic effects in cold-adapted (CA) rats. The response to beta receptor stimulation by isoproterenol in the isolated hind-limbs of CA rats was slightly diminished. Oxygen consumption and lactate production were reduced in CA rats after beta receptor stimulation. Noradrenalin infusion caused less vasoconstriction in CA rats than in the controls (CO). Desensitization of alpha and beta receptors due to chronic sympathetic overstimulation may be the underlying cause of these observations. Compared with the controls, metabolism was enhanced in perfused hind-limbs of CA rats with an active nervous system. Decreased vascular resistance due to the lower perfusion pressure in CA rats might contribute to this increased metabolism. PMID- 6250963 TI - Altered calcitonin sensitivity in thyroid disorders. PMID- 6250964 TI - Association between serum insulin, serum somatomedin and liver receptors for human growth hormone in streptozotocin diabetes. AB - Streptozotocin-induced diabetes in the female rat caused a decrease in the serum level of somatomedin (Sm), measured by radioreceptor assay. The decrease was reversed by insulin therapy. In diabetes of varying severity, serum insulin and Sm levels showed highly significant association up to the insulin concentration (18 microU/ml) corresponding to normal serum Sm (1 U/ml). Similarly, the hepatic binding of human growth hormone (hGH) showed highly significant association with serum Sm levels up to the degree of binding (7% of tracer) corresponding to normal serum Sm. Binding of hGH to normal liver was about 12% of tracer. These results suggest that insulin might regulate serum Sm via its effect on liver lactogenic receptors, and that about half of these receptors are "spare", or in excess of those required to maintain normal serum Sm levels. PMID- 6250965 TI - Elevated plasma and tissue concentrations of beta-endorphin and beta-lipotropin associated with an ectopic ACTH-producing lung tumor. AB - beta-Endorphin- and ACTH-like immunoreactive peptides were measured in plasma and certain tissues of a patient suffering from an oat-cell-carcinoma of the lungs and Cushing's syndrome. Using sensitive radioimmunoassays in combination with gel filtration, highly elevated levels of beta-endorphin, beta-lipotropin (beta-LPH), alpha-melanotropin (alpha-MSH) and ACTH were found. PMID- 6250967 TI - The kinetics of the interaction of a helix-destabilizing protein from roe-deer liver with DNA and the influence of phosphorylation. AB - The kinetics of the interaction of the DNA double-helix-destabilizing protein from roe-deer liver with different DNAs revealed a fast phase which is observed both by the increase in A260 of the DNA and the quenching of the protein intrinsic fluorescence. A slow phase with a smaller amplitude is only recorded by the increase of A260.--The protein contains slightly less than two phosphate groups per molecule, removal of one of which by alkaline phosphatase does not affect its activity; however, removal of both phosphates decreases the DNA unwinding property significantly. A similar decrease in activity is also revealed upon incorporation of an additional phosphate by cAMP-dependent protein kinase I. -Results of the protection of poly[d(A--T)] from DNase I digestion by the protein are in favor of a migration of the protein along the DNA. PMID- 6250966 TI - Inhibition of the cytochrome c/cytochrome c oxidase system by cytochrome c derivatives and related fragments. AB - The oxidation of ferrocytochrome c mediated by cytochrome c oxidase was investigated in the presence of ferricytochrome c, trifluoroacetyl-cytochrome c, the heme fragments Hse65-[1-65] and Hse80-[1-80] and their respective porphyrin derivatives, as well as carboxymethylated apoprotein and related fragments, polycations, salts and neutral additives. The inhibition of the redox reaction by salts and neutral molecules, even if in theoretical agreement with their effect on electrostatic interactions, may alternatively be interpreted in terms of hydrophobicity. The latter can account for the inhibitory properties of trifluoroacetylated ferricytochrome c, similar to those of ferricytochrome c. On the assumption that the inhibitory properties of some of the investigated derivatives monitor their binding affinities to the cytochrome c oxidase at the cytochrome c binding sites, the experimental results do not confirm a primarily electrostatic character for the cytochrome c/cytochrome c oxidase association process. Strong indication was found that the cytochrome c C-terminal sequence is critically involved in the complex formation. Conformational studies by circular dichroism measurements and IR spectroscopy in solution and in solid state respectively, show that some of the derivatives examined may possibly acqkuire in the binding process to the oxidase, as secondary structure similar to that present in the native cytochrome c. PMID- 6250968 TI - On the heterogeneity of vertebrate cytochrome c oxidase polypeptide chain composition. PMID- 6250969 TI - Influencing mental health policy: the MHA approach. AB - The Mental Health Association was founded in 1909 as a citizen advocate organization for the mentally ill. Today it embraces more than a million members in nearly 850 chapters nationwide and conducts numerous programs designed to prevent mental illness, promote mental health, and improve mental health services. In recent years it has played an increasingly active role in influencing mental health policy at the federal level. This article focuses on the association's activities in the political arena. PMID- 6250970 TI - Study to rate IC performance. PMID- 6250971 TI - Recombinant DNA and medical progress. AB - In the extensive debate surrounding recombinant DNA research, the significant contributions it has already made and their potential for directly affecting medical practice are often lost. The recombinant techniques are described in the context of the already achieved "manufacture" of highly pure insulin and human growth hormone and their promise for practical application in diagnosis and therapy. PMID- 6250973 TI - Iatrogenic hepatic injury. AB - Liver injury produced by therapeutic drugs is common, and has been increasing in incidence. Drug induced injury can mimic almost all varieties of liver disease. These conditions include cholestasis, steatosis, granulomas, acute and chronic hepatitis, cirrhosis, vascular disorders, and tumors. When confronted with a patient suffering from liver disease, it is imperative for the physician to obtain an accurate history of drug administration. PMID- 6250972 TI - Varicella vaccination: where do we go from here? AB - Although meager knowledge of the virus raises serious safety questions, the risk of death from varicella in immunocompromised children justifies further trials. In the meantime, passive immunization is a safe and relatively effective alternative. PMID- 6250974 TI - Multiple atypical acinar cell nodules of the pancreas. AB - Although acinar cell nodules of the pancreas have been described in rats given carcinogenic chemicals, similar nodules have not been reported in humans. This report describes two cases of nodular acinar cell lesions in the pancreas in patients who died of insulin secreting islet cell adenoma and of bronchogenic carcinoma. The lesions consisted of multiple nodules that were well demarcated from the surrounding acinar tissue and were composed of zymogen granule containing acinar cells with a pale to pink cytoplasm. The significance of these atypical acinar cell nodules in regard to their being possible precursor lesions of acinar cell carcinoma of the pancreas is discussed. PMID- 6250975 TI - Separation of interleaved nerve spike trains in a noisy channel. PMID- 6250976 TI - Feline sarcoma virus induced in vitro progression from premalignant to neoplastic transformation of human diploid cells. AB - Human diploid cells morphologically transformed by feline sarcoma virus were serially propagated under selective cell culture conditions. When injected into nude mice prior to passage in soft agar (0.35%), morphologically transformed cells did not produce tumors. However, when propagated under selective cell culture conditions, transformed cells grew in soft agar and, when injected subcutaneously into the subcapsular region of the n mu/n mu mice, produced neoplastic nodules histopathologically interpreted as fibromas. Karyological examination of cell populations grown out from the tumors confirmed that the tumors were composed of human cells. Examination of electron micrographs of the excised tumor tissue revealed the presence of budding virus particles. Tumor cells isolated from nude mice and morphologically transformed cells both contained the feline oncornavirus-associatied cell membrane antigen. It was concluded that expression of feline oncornavirus-associated cell membrane antigen is associated with an early stage of feline retrovirus-induced carcinogenesis, namely focus formation. In addition, it was shown that FeLV-FeSV can induce morphological transformation in human cells in vitro and that there is a requirement for the cells to passage through soft agar before subsequent tumor formation (neoplastic transformation) can be demonstrated. PMID- 6250977 TI - Influence of various immunomodulators on the induction of experimental autoimmune encephalomyelitis in Lewis rats. PMID- 6250978 TI - Kidney, liver and erythrocyte membrane Na+-K+ adenosine triphosphatase in oral contraceptive treated rats. PMID- 6250979 TI - Electrophysiological study of peripheral nerves in secondary polycythemia. PMID- 6250980 TI - Concentrations of cefotaxime in skin. PMID- 6250981 TI - Cefotaxime pharmacokinetics following a single intravenous dose to patients with varying renal function. AB - The pharmacokinetics of cefotaxime (HR 756) were investigated in two groups of patients (Groups I and II) with creatinine clearances of greater than or equal to 60 and < 60 ml/min per 1.73 m2 respectively. Each of the 24 patients included in the study received 0.5 g or 1.0 g cefotaxime intravenously as a bolus injection. The decline of serum concentrations was biphasic in all patients, and the data were fitted to the pharmacokinetic two-compartment model. The mean distribution and elimination half-lives of cefotaxime in individuals in Group I were 0.2 and 1.2 hours respectively. In the uremic individuals, the pharmacokinetic parametes did not differ markedly from those in normal subjects, except when renal function was markedly reduced. In severe renal impairment, the elimination half-life increased to 8.3 hours. Cumulative 24-hour urinary excretion accounted for a mean of 59% of the dose in normal individuals, and from 0.3 to 36% of the dose in uremic individuals. Incomplete recovery of intact drug in urine of normal individuals reflects excretion by an extrarenal pathway, possibly as desacetyl cefotaxime. Urine levels were greater than the minimum inhibitory concentrations for susceptible organisms for at least eight hours after dosing in all individuals who produced urine. Because of the relatively small effect of renal impairment on the pharmacokinetics of cefotaxime, dose reduction is necessary only in cases of severe renal impairment. PMID- 6250982 TI - [Diffusion of cefotaxime in different tissues of the urogenital tract (author's transl)]. AB - Within the framework of perioperative prophylaxis against infections, serum and tissue concentrations were measured following an i. v. bolus injection of 2.0 g of cefotaxime in 25 patients with a prostatic adenoma. The mean serum concentrations were 64.9 microgram/ml, 56.6 microgram/ml, 45.2 microgram/ml, 18.2 microgram/ml and 19.9 microgram/ml 30, 60, 90, 120 and 150 minutes respectively following the injection. The corresponding concentrations in the prostatic adenoma tissue were 8.8 microgram/g, 15.3 microgram/g, 22.9 microgram/g, 4.3 microgram/g and 2.7 microgram/g respectively. The tissue concentrations in ten testes from six patients were measured in a similar way. The maximum concentration (5.4 microgram/g) was also found to occur 90 minutes after the injection. We found very different values, ranging from 0.3 microgram/g to 39.6 microgram/g, in eight kidneys as a result of greatly differing diagnoses and function. Average concentrations of 9.2 microgram/g to 0.8 microgram/g in the ureter, fatty tissue and muscle tissue were within the therapeutically effective range. The cefotaxime concentrations found in serum and tissue lead us to expect successful therapy when cefotaxime is used to treat bacterial infections with sensitive pathogens in the urogenital tract. PMID- 6250983 TI - Similar effects of prolactin and dbcAMP upon human spermatozoa metabolism. AB - Studies were carried out of the effects of prolactin (0.5-1.0 mU) and 3'5' dibutyryl cyclic AMP -(dbcAMP) (100-500 ng) on oxygen uptake and (U-14C) glucose and (1-14C) acetate utilization by human spermatozoa. Both molecules induce a significant increase (P < 0.01) in oxygen uptake when acetate, glucose, pyruvate and lactate were used as substrates, although differences were noted in the induction effect depending on the substrate used (Tukey's multiple comparisons after ANOVA) (P < 0.01). The production of 14CO2 from glucose and labelled acetate was also statistically increased (P < 0.01) by prolactin (from 15.15 to 25.32 nmoles CO2/hour/10(8) sperm cells) as well as by dbcAMP (15.15 to 34.95 nmoles CO2/hour/10(8) sperm cells). From these results we conclude that the activator effects of prolactin and dbcAMP on human spermatozoa with respect to the studied parameters are similar and that prolactin may be an activator of spermatic adenylyl cyclase. PMID- 6250985 TI - Cyclic nucleotides vary by area in the retina and pigmented epithelium of the human and monkey. AB - Cyclic GMP and cyclic AMP are present in lower concentrations in the central (macular) region of the neural retina of the human and monkey than in other areas. This pattern approximates the distribution of rod photoreceptor cells. Surprisingly, an inverse gradient of cyclic GMP concentration is observed in the pigmented epithelium. Levels in the central region are over fourfold higher than in cells in the periphery, offering the first evidence of biochemical differences in this embryologically uniform cell type. PMID- 6250984 TI - Progress on the EBV front. PMID- 6250986 TI - Induction of cell-mediated immunity in herpes simplex virus keratitis. Kinetics of lymphocyte transformation and the effect of antiviral antibody. AB - The in vitro lymphoproliferative responses to herpes simplex virus (HSV) antigens were followed in rabbits with herpesvirus infection of the cornea. The proliferative cellular responses occurred early in infection and were demonstrated by lymphoid cells from the local lymph nodes at day 5, the peripheral blood at day 11, and the spleen after day 14. The presence of autologous serum antibodies suppressed lymphoproliferative responses of the lymph node lymphocytes to HSV antigens early in infection at day 5, the time at which antibody production is first noted. Peripheral blood and spleen cells were not appreciably influenced at early time periods. However at 7 months after infection, the presence of autologous serum antibodies stimulated spleen lymphocytes from animals with recurrent disease. These results indicate that antiviral antibodies can affect the cellular immune response in herpesvirus infections by modulating the lymphoproliferative response to herpes antigens. PMID- 6250987 TI - Special characteristics of the polar regions of the rat lens: morphology and phosphatase histochemistry. AB - Ultrastructural analyses of the normal rat lens revealed a number of characteristics present regionally within the anterior and posterior polar regions: (1) elaborate folding of the plasma membrane, including numerous microvillar processes; (2) wide intercellular spaces at basolateral cell borders; (3) concentrations of mitochondria; and (4) ouabain-sensitive Na-K-ATPase activity. These features, confined primarily to the suture systems and the anterior epithelium, suggested a cortical as well as an epithelial involvement in ion-linked fluid transport, supporting recent physiological investigations of the lens. Acid phosphatase localized in aggregations of smooth endoplasmic reticulum at the lens fiber ends suggested that this micro-organelle may be a source of acid hydrolases in the normal lens. PMID- 6250988 TI - Ultrastructure of intracytoplasmic particles in a Burkitt's lymphoma cell line. AB - Electron microscopic examination of a Burkitt's-lymphoma-derived cell line, P3HR 1, repeatedly revealed clusters of membrane-free nucleoids within the cytoplasmic matrix. The particles possessed an electron-lucent center surrounded by two layers - a dense ring and a fuzzy broad outer layer. PMID- 6250989 TI - Identification of Tettnang virus ('possible arbovirus') as mouse hepatitis virus. AB - Virus isolation attempts in specific-pathogen-free suckling mice (strain ICR) yielded 21 virus strains initially shown to be closely related to or identical with Tettnang virus. Subsequent studies showed them, as well as standard strains of Tettnang virus, to be closely related to or identical with mouse hepatitis virus. Tettnang virus is not an arbovirus. PMID- 6250990 TI - Biological properties of Junin virus proteins. I. Identification of the immunogenic glycoprotein. AB - Purified Junin virus was disrupted by nonionic detergent treatment (Triton X 100), and subviral components were separated by ultracentrifugation. Only the soluble fraction, containing all of the major glycoprotein (mol.wt. 38,000), induced the formation of neutralizing antibodies in laboratory animals and protected them against subsequent challenge with live virus. Thus, the glycoprotein is the antigen responsible for these immunologic responses. PMID- 6250991 TI - Populations of infectious virus produced during avian adenovirus-associated virus infection. AB - Multiple rounds of infection in vitro or in vivo with avian adenovirus-associated virus (AvA-AV) and avian adenovirus (AvAV) result in production of both heavy (H) and light (L) infectious forms. In this study, the infectious AvA-AV progeny produced at different hours during recombined dual infection of cells with either H or L AvA-AV and AvAV was determined by equilibrium CSCl centrifugation and infectivity assay. In both types of infection, H virions were found early, both intra- and extracellularly, whereas L virions were found late. The data iondicate an H to L particle density shift during infection. Virus-specified cell-dependent factors mediated the process extracellularly, as activity was detected in infected cell-conditioned medium and in lysates of infected cells but not in medium or components of uninfected cells. The shift in density was accompanied by a conversion in particle type. H and L virions differed in size and conformation as evidenced by differences in serological cross-reactivity and physical-chemical stability during heat inactivation, ultrasonic disruption and DNA extraction. PMID- 6250992 TI - Isolation and genetic analysis of temperature-sensitive mutants of rhinovirus type 2. AB - Temperature-sensitive mutants of human rhinovirus type 2 were isolated by random clonings of mutagenized virus. All mutants were stable. Temperature sensitivity was not affected by different host cell systems. Complementation was observed in 3 of 10 dual viral mixtures, with complementation indices being as high as 4.0. Recombination frequencies fluctuated widely between experiments with different mutants, but positive recombination occurred with mean frequencies ranging from 0.03 to 1.25%. The complementation and recombination results obtained are similar to those reported for other picornaviruses. PMID- 6250993 TI - An additional role for the outer nuclear membrane in the morphogenesis of herpes simplex virus. AB - Ultrastructural study of MRC-5 cells infected by herpes simplex virus yielded several examples of physical continuity between the outer nuclear membrane and the envelope of viral particles in the perinuclear cisterna, suggesting a fusion between the two. Such virions would thus lose their envelope and enter the cytoplasm as naked capsids. Fusion first occurred at 6-8 h postinfection (p.i.), while naked cytoplasmic capsids appeared at 6 h p.i. Since nuclear membrane disruption was not observed until 24 h p.i., it is unlikely to account for the early appearance of these capsids. Thus, in addition to its other roles, the outer nuclear membrane may be involved in naked cytoplasmic capsid production via a fusion event. PMID- 6250994 TI - Biophysical studies of erythrocyte membranes from patients with duchenne muscular dystrophy. AB - Lipid-soluble spin labels were used to probe the fluidity of membrane lipids in erythrocyte membranes from patients with Duchenne muscular dystrophy. A greater mobility of spin label motion was noticed at the surface of the Duchenne erythrocyte membranes in comparison with the similary labeled normal human erythrocytes. Changes in the protein conformation and/or protein-lipid organization, as a consequence of an altered membrane lipid fluidity, have been demonstrated by the use of a sulfhydryl group specific protein spin label. Strongly immobilized sulfhydryl groups appear to be located both at the membrane surface and deep within the lipid bilayer. The ratio of the spectral amplitude of the spin label attached to weakly immobilized sulfhydryl groups to that of strongly immobilized SH-groups is significantly greater in Duchenne membranes, compared to those of controls. These studies suggest alterations in lipid-protein organization at the surface of Duchenne erythrocytes, indicating that Duchenne muscular dystrophy may be a disease resulting from a membrane abnormality at the molecular level. PMID- 6250995 TI - Relative risk factors in the treatment of juvenile nasopharyngeal angiofibroma. AB - The potentially fatal complications associated with surgery and radiation therapy in the management of juvenile nasopharyngeal angiofibroma (JNA) are analyzed. Quantitative risk factors established from review of the literature suggest a risk of potentially fatal complications of 1 in 3,000 from general anesthesia, 1 in 1,600 from arteriography, 1 in 160 from blood transfusion, and 1 in 500 from the surgical procedure itself. The total of these risks is comparable to the 1% lifetime risk of developing a radiation-induced tumor after radiation therapy. The time pattern of these complications differs in that fatal radiation-induced complications are delayed, whereas the risks associated with surgery, general anesthesia, and blood transfusion are more immediate. However, it is suggested that treatment-related risks of fatal complications are of a similar order of magnitude for surgery and for radiation therapy in the management of JNA. PMID- 6250996 TI - The pathology of head and neck tumors: neoplasms of cartilage, bone, and the notochord, part 7. AB - Neoplasms of the supporting tissues in the head and neck are outnumbered by their histologic counterparts in the trunk and extremities. This is especially true for tumors of bone, cartilage, and the remnants of the notochord. Malignancies occurring in all three tissues, however, are just as lethal as those sited elsewhere. Chondrosarcomas and osteogenic sarcomas of the facial bones are resistant to all conventional modes of therapy, manifest many recurrences, and have an often protracted morbidity. The craniocervical chordoma manifests a similar biologic course. For the tumors of cartilaginous origin and the osteogenic sarcomas, the initial surgical attempt at removal is of key importance. Neoplasms present at the margins of resection have a poor prognosis. Chorodomas are not likely to be cured by any modality. PMID- 6250999 TI - The stress audit: identifying the stressors of ICU nursing. PMID- 6250998 TI - A case of multiple skeletal anomalies, ectodermal dysplasia, and severe growth and mental retardation. AB - A 17-year-old female patient presented extreme growth failure, severe microcephaly and developmental delay, and a unique pattern of congenital anomalies, predominantly of the skeleton and the skin. Prominent findings included hidrotic ectodermal dysplasia with virtually complete absence of body hair, ichthyosiform hyperkeratosis of the skin over the lower legs, dysplasia of toenails; small hands and feet with with short fifth fingers and toes complete cutaneous syndactyly between toes 4 and 5; in X-rays, fusion of several vertebral bodies, humero-radial ankylosis, fusion between talus and navicular bone, lunate and triquetral, and proximal fusion between metacarpals 4 and 5; and luxation of the right femoral head. The patient might represent a hitherto undescribed malformation syndrome of unknown etiology. PMID- 6250997 TI - Hypophosphatemic vitamin D resistant rickets (phosphate diabetes): bone mineral problems studied by 125I-computed tomography and microradiography. AB - 125I-computed tomography (CT) for the bone mineral analysis of the radius was performed on 9 children with vitamin D resistant hypophosphatemic rickets (VDRR) treated with vitamin D in pharmacological doses. Trabecular bone density was increased in 1 patient and normal in all others. The cortical width of the diaphysis of the radius was decreased, and the cross sectional area of the bone increased, but the total amount of compat bone mineral in the cross section was normal. Measurements of the second metacarpal bone on X-rays of the hand revealed similar findings. Microradiographic and histological examinations of the fibula on 9 different patients also treated with vitamin D showed grossly abnormal mineralization of bone tissue with a perilacunar mineral deficit. It is concluded, that the amount of compact bone and trabecular bone is not decreased in children with VDRR. The normal mineral content determined by CT and the impaired mineralization of the bone material examined by microradiography indicate an over-abundance of incompletely mineralized bone. PMID- 6251001 TI - Building a research alliance: a necessary first step. PMID- 6251000 TI - The design of a stress management program for Stanford intensive care nurses. PMID- 6251002 TI - Coping with stress through an "on-site" running program for Stanford ICU nurses. PMID- 6251003 TI - Personalogical measures to assess program effects: a case study. PMID- 6251004 TI - Management actions to humanize the health care environment. PMID- 6251005 TI - Work-site interventions for stress reduction. PMID- 6251006 TI - Stress and stress management: an overview. PMID- 6251007 TI - "Pay-offs" and "trade-offs": reflections of a nursing administrator and a nursing educator on a collaborative study in the practice of nursing. PMID- 6251008 TI - Stress and the nurse: a selected bibliography. PMID- 6251009 TI - Occupational stress of intensive care nurses & air traffic controllers: review of related studies. PMID- 6251010 TI - Evaluating students' clinical performance: using videotape to establish rater reliability. PMID- 6251011 TI - A survey of obstetrical teaching strategies in baccalaureate schools of nursing. PMID- 6251012 TI - Skill acquisition in nurse-midwifery education. PMID- 6251013 TI - The process of change in curriculum evaluation. PMID- 6251014 TI - Ambulatory care and the integrated curriculum. PMID- 6251015 TI - Student and faculty perspectives on the role of a nursing instructor. PMID- 6251016 TI - An approach to analysis of a symptom: an educational experience. PMID- 6251017 TI - Feline leukemia. PMID- 6251018 TI - Antibiotics that specifically block translation in virus-infected cells. AB - Several antibiotics including anthelmycin, blasticidin S, destomycin A, gougerotin, hygromycin B and edeine complex, known to powerfully block translation in cell-free systems, did neither inhibit protein synthesis in intact mouse L and 3T6 cells, nor in hamster BHK 21 cells, due to failure to cross the cell plasma membrane. However, after viral infection, these antibiotics exhibited a marked blockade of translation, that is related to the permeability changes induced by viral infection. The inhibition of protein synthesis by hygromycin B in virus-infected cells was studied over the time course of infection, both in encephalomyocarditis virus-infected mouse L cells and in Semliki forest virus infected hamster BHK cells. We have observed that the entry of hygromycin B into virus-infected cells parallels the inhibition of cellular protein synthesis, i.e., the cells became permeable to this antibiotic at the time the shut-off of host translation occurred. A marked inhibition of picornavirus RNA synthesis by hygromycin B was also noticed, likely as a consequence of the inhibition of the viral replicase synthesis. Finally, a reduction in the virus yield by treatment of virus-infected cells with several antibiotics is also described. All these observations are considered in the context of the interference of viral infection with cellular functions and the potential use of inhibitors non-permeable to normal cells as antiviral agents. PMID- 6251019 TI - 6 beta-Halopenicillanic acids, a group of beta-lactamase inhibitors. PMID- 6251020 TI - Inhibitory effect of polymyxin B on prodigiosin biosynthesis in Serratia marcescens. PMID- 6251021 TI - Chemotherapy with cefotaxime: how to avoid selection of Pseudomonas aeruginosa. PMID- 6251022 TI - CSF concentrations of ketoconazole. PMID- 6251023 TI - Duration of pivmecillinam treatment of urinary tract infections in hospital in patients. PMID- 6251024 TI - High pressure liquid chromatographic determination of vitamin D3 in instant nonfat dried milk. AB - Vitamin D3 was determined in commercially fortified instant nonfat dried milk by using normal phase high pressure liquid chromatography (HPLC). The sample was extracted with dichloromethane with sodium phosphate tribasic solution added. The sample was cleaned up by using a Sep-Pak silica cartridge and then a microparticulate column containing 10 micrometer Partisil-10 PAC packing material. The final analysis was performed by using a normal phase HPLC system with 10 micrometer LiChrosorb NH2 column. Recovery of vitamin D3 at levels as low as 10000 IU/kg was 97.7% with a standard deviation of 3.9%. PMID- 6251025 TI - Structure of the Escherichia coli K2 capsular antigen, a teichoic acid-like polymer. AB - The primary structure of the K2 antigen of Escherichia coli was elucidated by composition, alkaline fragmentation, dephosphorylation with hydrofluoric acid, periodate oxidation, and methylation analysis. The polymer contains galactose in the pyranosidic and furanosidic ring form. It consists of phosphogaolactopyranosyl glycerol and phosphagalactofuranosyl glycerol units in a molar ratio of 2:1. The sequence of these units is not known. The structure of the K2 antigen is reminiscent of that of certain teichoic acids of gram-positive bacteria. Using microprecipitation, it was shown that in the polymer galactoside is immunodominant. PMID- 6251026 TI - Physical mapping and expression of hybrid plasmids carrying chromosomal beta lactamase genes of Escherichia coli K-12. AB - Hybrid plasmids carrying the ampC gene of Escherichia coli K-12 that codes for the chromosomal beta-lactamase were physically studied. The ampC gene was mapped to a deoxyribonucleic acid segment encompassing 1,370 base pairs. The mapping was facilitated by the isolation of a plasmid carrying an insertion of the transposable element gamma delta (gamma delta) close to ampC. The ampA1 mutation, which increases the expression of ampC by a factor of about 20, was localized to a 370-base pair segment of the 1,370-base pair deoxyribonucleic acid segment that contains the ampC gene. Using a minicell protein labeling system, it was seen that plasmids carrying either ampA+, ampC, or ampA1 and ampC coded for a 36,000 dalton protein which comigrated with purified chromosomal beta-lactamase. In cells carrying plasmids that bore the ampA1 allele, the production of this protein was greater. In addition, a protein with a slightly higher molecular weight (38,000) was expressed by both ampA+ ampC and ampA1 ampC plasmids in this protein labeling system. This protein might represent a precursor form of chromosomal beta-lactamasee. From E. coli K-12 strains carrying the ampA1 allele, second-step mutants were isolated that hyperproduced chromosomal beta-lactamase. By reciprocal recombination, plasmid derivatives were isolated that carried these mutations. Two second-step regulatory mutations mapped within the same 370-base pair region as ampA1. This piece of deoxyribonucleic acid therefore contains ampA, a control sequence region for ampC. PMID- 6251027 TI - Tn2301, a transposon construct carrying the entire transfer region of the F plasmid. AB - The largest R . BamHI fragment of the plasmid F, which carries the entire F conjugation system, has been cloned into the single R . BamHI site of the ampicillin (Ap) resistance transposon TN1. pDS1106 (ColE1 mob::Tn1) was the vector plasmid, and the resultant conjugative plasmid, pED830, was characterized both genetically and by restriction enzyme analysis. The transposon construct, denoted Tn2301, was transposable at frequencies similar to Tn1 to small nonconjugative plasmids or to the Escherichia coli host chromosome. In the former case, Apr conjugative plasmids were obtained, whereas in the latter case, Hfr strains resulted. Representative Hfr strains were characterized by quantitative and interrupted mating experiments. Extension of this technique for Hfvr formation should aid chromosome mapping both in E. coli and in other bacterial genera. PMID- 6251028 TI - Pyridine nucleotide control and subunit structure of phosphoribulokinase from photosynthetic bacteria. AB - With one exception, phosphoribulokinase from the Rhodospirillaceae requires reduced nicotinamide adenine dinucleotide for maximum activity. This mode of regulation is unique to the facultatively anaerobic photoorganotrophic photosynthetic bacteria, since the phosphoribulokinase from oxygen-evolving photosynthetic species is not subject to activation by reduced nicotinamide adenine dinucleotide. The enzyme was purified of fructose bisphosphatase activity from Rhodopseudomonas capsulata by means of affinity chromatography and was shown to have a native molecular weight of about 220,000. The homogeneous enzyme is composed of a single size polypeptide of 36,000 molecular weight. This study represents the first time the subunit structure of phosphoribulokinase has been determined from any source. PMID- 6251029 TI - Genetic organization of the broad-host-range IncP-1 plasmid R751. AB - We have identified regions encoding conjugal transfer, plasmid maintenance, and trimethoprim resistance on the IncP-1 plasmid R751 by complementation tests with cloned deoxyribonucleic acid fragments and self-replicating derivatives constructed in vitro. The genes for replication and transfer show a scattered organization similar to that previously determined for RK2, another IncP-1 plasmid. Derivatives of RK2 are able to complement R751 derivatives defective in these functions. Restriction enzyme cleavage sites in R751 deoxyribonucleic acid are clustered in regions of the plasmid physical map. Neither region is required for plasmid maintenance or transfer, although one determines resistance to trimethoprim. A similar clustering of cleavage sites is seen with RK2, which nevertheless has a very different restriction map. PMID- 6251030 TI - Chimeric streptococcal plasmids and their use as molecular cloning vehicles in Streptococcus sanguis (Challis). AB - Chimeric plasmids, which were useful as cloning vehicles in a Streptococcus sanguis (Challis) host vector system, have been constructed. By using three different strategies of restriction endonuclease digestion and ligation, a deoxyribonucleic acid (DNA) fragment bearing an erythromycin resistance determinant was ligated in vitro to a phenotypially cryptic plasmid from Streptococcus ferus. Recombinant plasmids could be recovered after transformation of S. sanguis (Challis) with these preparations. Three useful chimeras were constructed. pVA680, 5.5 megadaltons in size, contained a single KpnI site into which passenger DNA may be spliced. pVA736, 5.0 megadaltons in size, contained single EcoRI, HindIII, and KpnI sites into which passenger DNA may be spliced. The EcoRI and KpnI sites of pVA736 may be used in combination with one another when ligating DNA into this plasmid. pVA738, 3.7 megadaltons in size, contained single HindIII and AvaI sites into which passenger DNA may be spliced. pVA680, pVA736, and pVA738 were stably maintained as multicopy plasmids in S. sanguis (Challis). None of them continued to replicate (amplify) in chloramphenicol treated cells. By using pVA736 as a vector, we have cloned a chloramphenicol resistance determinant obtained from a large, conjugative streptococcal R plasmid. In addition, chromosomal DNA sequences from Streptococcus mutans have been inserted into pVA736 by using the KpnI-EcoRI site combination. PMID- 6251031 TI - Genetic mapping of the Salmonella typhimurium pepB locus. AB - Transposon technology has been used to map the pepB locus of Salmonella typhimurium. This locus is cotransducible by phage P22 with glyA and strB at min 56 on the Salmonella genetic map. The gene order is strB pepB glyA. PMID- 6251032 TI - Cloning of the URA1 gene of Saccharomyces cerevisiae. AB - A 5.7-kilobase segment of Saccharomyces cerevisiae deoxyribonucleic acid which complements both the yeast ura1 and Escherichia coli pyrD mutations in dihydroorotate dehydrogenase has been cloned in plasmid YRp7. PMID- 6251033 TI - Cooperation of cytochalasin D and anti-microtubular agents in stimulating superoxide anion production in polymorphonuclear leukocytes. AB - Superoxide anion production in polymorphonuclear leukocytes obtained from guinea pig peritoneal cavities was stimulated by treatment with 5 microgram/ml of cytochalasin D in vitro. The stimulation was further enhanced by the addition of either 10(-5)-10(-7) M vinblastine or 10(-3)-10(-8) M colchicine to cytochalasin D. Higher concentrations of these anti-microtubular agents were inhibitory to the stimulating effect of cytochalasin D on the superoxide anion production, while lower concentrations had almost no effect. In the resting leukocytes, i.e. without cytochalasin D, the anti-microtubular agents by themselves had no effect on the superoxide anion production. The cooperation of cytochalasin D and the anti-microtubular agents was also observed in the stimulation of NADPH oxidase activity and bactericidal function of the leukocytes. PMID- 6251034 TI - Circular dichroism studies on flavoproteins containing covalently bound coenzymes. AB - Absorption and circular dichroism spectra of cholesterol oxidase from Schizophyllum commune and choline oxidase from Alcaligenes sp. were measured and compared. The prosthetic group of cholesterol oxidase is 8 alpha-[N(1)-histidyl] FAD (1, 2), while that of choline oxidase is 8 alpha-[N(3)-histidyl]-FAD (3). In the CD spectra of the two enzymes in either the oxidized or reduced state, the corresponding bands in the visible region are of approximately the same intensity and shape but of opposite sign. A notable feature in the CD spectra of the two enzymes after light irradiation is the appearance of a CD band in the longer wavelength region (550-650 nm) and the opposite signs of the CD band in this region in the two enzymes. The similarity of the shape and intensity of the CD spectra of the two enzymes suggests that the environments surrounding the flavin moieties are very similar, and the sign reversal of the CD bands suggests that the mutual orientations between the transition moment of flavin and that of its environment differ in the two enzymes. PMID- 6251035 TI - Purification and properties of thiamine pyrophosphokinase in Paracoccus denitrificans. AB - The existence of thiamine pyrophosphokinase [EC 2.7.6.2] in procaryotic cells was first demonstrated in Paracoccus denitrificans (J. Bacteriol, (1976) 126, 1030 1036). The enzyme was therefore purified from this organism to determine its molecular structure and properties. Thiamine pyrophosphokinase which was purified 620-fold from P. denitrificans showed a single band on both polyacrylamide and sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis, and the molecular weight in the latter case was calculated to be 23,000. Gel filtration analysis using Sephadex G-150 gave a molecular weight of 44,000, indicating that this enzyme contains at least two identical subunits. Although sedimentation equilibrium analysis gave a molecular weight of 96,000, indirect evidence suggests that the form having this molecular weight is an aggregate of the functional dimer. The activity of the purified enzyme required thiamine, ATP, and Mg2+, and the enzyme catalyzed thepyrophosphorylation of thiamine by ATP. Km values for thiamine and ATP were 10 microM and 0.38 mM, respectively. The activity was competitively inhibited by pyrithiamine, giving a Ki value of 19 microM. Oxythiamine and chloroethylthiamine were very weak inhibitors of the enzyme. The activity was also inhibited by the product, TPP. PMID- 6251036 TI - Temperature sensitive phosphoproteins in rat cells transformed by a temperature sensitive mutant of rous sarcoma virus. AB - The localization of the src-encoded protein kinase was examined by fractionating cellular extracts from rat cells transformed by a wild type and a temperature sensitive mutant of Rous sarcoma virus (SR-A 3Y1 and ts68 3Y1 cells). It was found to be specifically localized in the post-microsomal supernatant (PMS) fraction. Furthermore, it was noticed that a protein with a molecular weight of 16,000 (16K-protein) in the PMS fraction was phosphorylated in vitro when the PMS fraction from ts68 3Y1 cells was preincubated at 33 degrees C, but not at 42 degrees C. This protein was phosphorylated when the fraction from SR-A 3Y1 cells was preincubated at 33 degrees C and at 42 degrees C. Similar temperature sensitive phosphorylation of 16K-protein was also observed in the PMS fraction from ts68 3Y1 cells labeled in vivo with [32P]orthophosphate at 33 degrees C. These results suggest that this 16K-protein might be a candidate for the endogenous acceptor for the src-encoded protein kinase. PMID- 6251037 TI - Steady-state kinetics of mouse DNA polymerase alpha. AB - Steady-state kinetic studies of DNA polymerase alpha purified from mouse myeloma MOPC104E cells have been carried out. The results of initial velocity analysis with or without sodium pyrophosphate, a product inhibitor, indicated that the reaction mechanism of this enzyme can be categorized as an ordered Bi Bi type where the concentration of the ternary complex is very low. PMID- 6251038 TI - Substrate specificity of nuclease TT1 from Thermus thermophilus HB8. AB - The substrate and the action mechanism of a nuclease named nuclease TT1, from the culture broth of an extreme thermophile, Thermus thermophilus HB8, were investigated. The enzyme is nonspecific for the sugar moiety and cleaves both single- and double-stranded DNAs, rRNA, tRNA and oligonucleotides irrespective of chain length to produce 5'-mononucleotides exonucleolitically. The action mechanism is processive and the enzyme shows no porality of degradation. The minimal unit as a substrate is a 5'-dinucleotide. The rate of hydrolysis is independent of a terminal phosphate group. The substrate lacking a 5'-phosphoryl group is degraded to leave the 5'-terminus and the penultimate nucleotide (NpN) as a core. The substrate possessing a 3'-phosphoryl group is degraded to leave the mononucleoside 5',3'-diphosphates (pNp). However, NpN and pNp are gradually degraded by a large dose of the enzyme to produce a 5'-mononucleotide. The enzyme is free from nonspecific phosphatase and phosphodiesterase activities. Application of this enzyme to determine the sequence of oligonucleotides is shown. PMID- 6251039 TI - Sterol-content lowering action of o-chlorobenzylchloride in yeast. AB - o-Chlorobenzylchloride, a simple aromatic halogen compound, was found to inhibit the growth of Saccharomyces cerevisiae and to lower the contents of sterols and fatty acids. The growth inhibition was considerably alleviated by the presence of sterols such as ergosterol and cholesterol and of unsaturated fatty acids such as oleate and linolenate. Inspection of effect of the inhibitor on the electron transport system related to the biosyntheses of these compounds revealed that the cytochrome contents and some enzyme activities in the system of the inhibited cells were much lower than those of the control cells. The features of the inhibition were similar to those of inhibition for other organisms by the hypocholesterolemic compounds such as triparanol and benzmalecene. PMID- 6251040 TI - Reversible dissociation of steroid hormone x receptor complexes by mercurial reagents. AB - Steroid hormone receptors contain a reactive sulfhydryl group (or groups) required for hormone binding. In the present study, the effects of several sulfhydryl-blocking reagents on hormone binding to aporeceptors and hormone x receptor complexes were compared, with the use of preparations of chick oviduct progesterone receptor and intestinal vitamin D receptor. N-Ethylmaleimide inhibited hormone binding to aporeceptors, whereas prior hormone binding protected against inactivation. In contrast, the mercurial reagent mersalyl both inhibited hormone binding to aporeceptors and dissociated hormone x receptor complexes. Complete dissociation of these complexes was achieved within 20 to 30 min at 0 degrees C. This process was a pseudo-first order reaction with a t 1/2 much less than the t 1/2 for hormone dissociation for either receptor at 0 degrees C. Hormone displacement was a general property of mercurial reagents; several organic mercurials as well as HgCl2 were effective. In contrast, sulfhydryl-alkylating agents (maleimides, iodoacetamide) and the disulfide 5,5' dithiobis(2-nitrobenzoate) were ineffective in displacing bound hormone from either progesterone or vitamin D receptors. Finally, hormone displacement by mersalyl was reversible; addition of excess thiol reagent displaced the bound mersalyl and regenerated hormone binding activity in good yield. This result suggests that mercurial reagents should prove useful in further study of steroid hormone receptors, for example in elution of receptors from steroid-affinity adsorbents. PMID- 6251041 TI - Calmodulin-dependent glycogen synthase kinase. AB - A cAMP-independent glycogen synthase kinase has been purified from rabbit liver. This kinase is completely dependent on the presence of calmodulin and Ca2+ for activity. Half-maximal activation required about 0.1 microM calmodulin. Complete inhibition was obtained in the presence of ethylene glycol bis(beta-aminoethyl ether)N,N,N',N'-tetraacetic acid or trifluoperazine. This calmodulin-dependent synthase kinase does not phosphorylate phosphorylase, myosin light chain, casein, or histone. It rapidly incorporates 0.4 to 0.5 mol of 32P/mol of synthase subunit into the NH2-terminal domain, resulting in partial inactivation of glycogen synthase. These results indicate the existence of a calmodulin-dependent kinase which may be specific for glycogen synthase. PMID- 6251042 TI - Enzyme-catalyzed DNA unwinding. The role of ATP in helicase III activity. AB - The enzyme helicase III catalyzes ATP-dependent unwinding of double-stranded DNA (Yarranto, G. T., Das, R. H., and Gefter, M. L. (1979) J. Biol. Chem. 254, 11997 12001). The free enzyme is able to bind to double- and single-stranded DNA. In the presence of ATP the enzyme can bind single- but not double-stranded DNA. The enzyme catalyzes an ADP-ATP exchange reaction in the absence of DNA. It is suggested that there is an enzyme.phosphate complex that discriminates between the two forms of DNA. These results are discussed in relation to a model that accounts for catalytic unwinding of DNA coupled to ATP hydrolysis. PMID- 6251043 TI - Mechanism of cyclic AMP effect on nutrient transport in Chinese hamster ovary cells. A genetic approach. AB - The effect of 8-bromo cyclic adenosine 3':5'-monophosphate (8-Br-cAMP) on sugar and amino acid transport was investigated in wild-type Chinese hamster ovary (CHO) cells and in mutants selected for resistance to cAMP inhibition of cell growth. In wild type cells, both 3-O-methyl-D-glucose and alpha-aminoisobutyric acid transport were decreased in cells treated for 24 h with 8-Br-cAMP; kinetic analysis indicated that a decrease in Vmax, without a significant change in Km, accounted for the lower transport capacity of 8-Br-cAMP treated cells. Among the different transport systems contributing to amino acid entry, "alanine" preferring transport system (system A) appeared to be specifically affected. The sensitivity of transport processes to 8-Br-cAMP was tested in three cAMP resistant cell lines. When tested for their capacity to phosphorylate histones in crude extracts, one strain had apparently normal amounts of protein kinase activity, one strain had a decreased enzyme sensitivity to cAMP, and one strain had little or no enzyme activity. In all three mutants, no effect of 8-Br-cAMP on 3-O-methyl glucose and alpha-aminoisobutyric acid transport could be observed, regardless of the level of cAMP-dependent protein kinase activity. These data do not indicate whether the effect of cAMP on nutrient transport in CHO cells is the cause or consequence of growth inhibition. However, they support the conclusion that, in CHO cells, the presence of a normally functioning cAMP-dependent protein kinase appears to be necessary but may not be sufficient to observe the effects of cAMP on nutrient transport as well as cell shape and cell growth. PMID- 6251044 TI - Interaction of 70 S ribosomes from Escherichia coli with spin-labeled N-Cbz-Phe tRNAPhe. An electron paramagnetic resonance study. AB - Two selectively spin-labeled Cbz-Phe-tRNAsPhe, one at position s4U8 and the other at position U33, have been used to study the dynamics of tRNA-ribosome interaction in the presence of poly(U) and factors washable from ribosomes. Upon binding to the ribosome, the correlation time of the spin label at position s4U8 decreases markedly while the same parameter for the label in the anticodon increases. The presence of poly(U) is not a prerequisite condition for the EPR spectral changes observed but larger variation occurs in the presence of factors washable from ribosomes. No variation in the correlation time is observed if uncharged spin-labeled tRNAPhe (on the s4U8 residue) is used in these experiments. Most of the ribosome-bound spin-labeled Cbz-Phe-tRNAPhe are puromycin-reactive, and consequently, the observed effect is manifested mainly at the ribosomal P site. These observations seem to suggest that the interaction between the N-blocked aminoacyl residue on the tRNA and the ribosome results in a conformational change on the tRNA, possibly involving tertiary interactions in a region close to s4U8. The role that the amino acid at the 3'-end can possibly play on this structural change is discussed. PMID- 6251045 TI - Salt-induced exposure of high affinity thyrotropin receptors on human and porcine thyroid membranes. AB - Thyropin binding to high affinity receptors on human and porcine membranes was studied at pH 7.4, 37 degrees C, in 10 mM Tris-HCl, 150 mM NaCl, 0.1% albumin. By preincubating the membranes in high salt concentration before binding studies, the number of high affinity receptors could be increased 4- to 8-fold. The salt induced exposure of high affinity TSH receptors was pH- and temperature-dependent and was maximal at pH 5.0, 37 degrees C in the presence of 1 M (NH4)2SO4. Other salts tested, including NaCl, HN4Cl, and Na2SO4, were also able to increase high affinity THS binding. The receptors exposed by salt were indistinguishable from those present on the membranes before such treatment. They had an affinity constant of 0.5 to 1 X 10(10 M-1, and a high TSH specificity with no inhibition of 125I-TSH binding in the presence of a thousandfold excess of gamma-globulin, thyroglobulin, corticotropin, cholera toxin, and gangliosides. Thyrotropin binding to low affinity TSH binding sites (affinity constant 1 to 3 X 10(7) M-1) measured at pH 6.0, 4 degrees C in 10 mM Tris/acetate, 0.1% albumin was unaltered by pre-exposure of membranes to high salt concentrations. These receptors had low TSH specificity and binding was inhibited by gamma-globulin, thyroglobulin, cholera toxin, and gangliosides. The salt-induced selective exposure of high affinity receptors with unaltered number of low affinity sites is further support for the existence of two separate TSH binding sites on thyroid membranes. PMID- 6251046 TI - Intracellular movement of cholesterol in rat adrenal cells. Kinetics and effects of inhibitors. PMID- 6251047 TI - The stereochemistry of peroxidase catalysis. PMID- 6251048 TI - Evidence of substantial separation of the catalytic and allosteric sites of AMP nucleosidase. PMID- 6251049 TI - Deoxyadenosine/deoxycytidine kinase from Bacillus subtilis. Purification, characterization, and physiological function. AB - Three different deoxyribonucleoside kinases with specificities toward thymidine, deoxyguanosine, and deoxyadenosine/deoxycytidine, respectively, are identified in Bacillus subtilis. The deoxyadenosin/deoxycytidine kinase is purified 950-fold employing blue Sepharose CL-6B column chromatography. The two deoxyribonucleoside kinase activities copurify and are present in the same band after polyacrylamide gel electrophoresis. The molecular weight is determined by gel filtration to be 47,000. Cytidine, adenosine, arabinosylcytosine, and arabinosyladenine are substrates for the enzyme. The activities toward these substrates are less than 20% of the activities obtained with deoxyadenosin and deoxycytidine. The deoxycytidine and deoxyadenosine saturation curves are hyperbolic with Km values for both nucleosides around 5 microM. The maximal velocities for the two deoxyribonucleosides are nearly identical with GTP as phosphate donor. GTP is the best donor showing hyperbolic saturation curves and Km values around 150 microM depending on the deoxyribonucleoside concentration. dATP and dCTP are inhibitors when GTP is the phosphate donor. They may both act as phosphate donors themselves. A divalent metal ion is required, Mg2+ giving the highest activity. A spontaneous mutant, selected as resistant to 5-fluorodeoxycytidine, lacks both deoxycytidine and deoxyadenosine kinase activity, while it retains normal activities toward deoxyguanosine, deoxyuridine, and thymidine. PMID- 6251050 TI - Definition of enzymic interaction domains on cytochrome c. Purification and activity of singly substituted carboxydinitrophenyl-lysine 7, 25, 73, 86, and 99 cytochromes c. PMID- 6251051 TI - Phosphatidylcholine vesicle reconstituted cytochrome P-450scc. Role of the membrane in control of activity and spin state of the cytochrome. AB - Cytochrome P-450scc from bovine adrenal cortex mitochondria was purified and reconstituted into phosphatidylcholine vesicles which varied in both cholesterol content and in the fatty acyl composition of the phospholipid. Under conditions of optimal ionic strength, pH, and excess adrenodoxin and adrenodoxin reductase, it was found that at a constant cholesterol: phospholipid ratio, the membrane composition had large effects on the rate of hemoprotein-catalyzed side chain cleavage of cholesterol. Rate effects were due to phospholipid-induced changes in the enzyme's Km for cholesterol, and not due to Vmax effects. Binding of cholesterol to cytochrome P-450 could also be monitored optically by measuring the fraction of enzyme in the high spin form. Dissociation constants determined in this manner for cholesterol binding in phospholipid of differing fatty acyl composition showed an excellent inverse correlation with the rates of pregnenolone formation in the same lipids (at constant cholesterol concentration) (see Fig. 6); thus, phospholipid exerts its rate effects by modulating the binding of cholesterol to the cytochrome. The membrane-mediated effects on spin state and activity mimic closely the effects seen in mitochondria isolated from adrenocorticotropic hormone-treated versus control adrenal cells. This behavior suggests to us that acute steroidogenic action of adrenocorticotropic hormone may be mediated through changes in the composition of the inner mitochondrial membrane in which cytochrome P-45scc is embedded. PMID- 6251052 TI - Skeletal muscle protein and amino acid metabolism in hereditary mouse muscular dystrophy. The role of disordered cyclic nucleotide metabolism in the accelerated alanine and glutamine formation and release. PMID- 6251053 TI - Purification of acetylcholine receptors, reconstitution into lipid vesicles, and study of agonist-induced cation channel regulation. AB - We report the purification of acetylcholine receptors with active agonist regulated cation channels from Torpedo californica electric organ tissue by five methods. In one method, previously used by others, contaminating proteins were removed from partially purified membranes by alkaline extraction, preserving membrane integrity throughout the procedure. In the other four methods, acetylcholine receptors were purified after solubalization with sodium cholate. The continual presence of soybean lipid in mixed micelles with cholate was required to prevent irreversible inactivation of the cation channel. Solubilized receptors were purified by affinity chromatography using either Naga naja siamensis toxin III or concanavalin A coupled to agarose. Sucrose gradient centrifugation was also used to purify solubilized receptors. The best method combined affinity chromatography on toxin-agarose and concanavalin A agarose. Receptors purified by all five methods were incorporated into soybean lipid vesicles by the cholate dialysis technique. The agonist-regulated cation channels of the receptors were equally active after reconstitution, independent of the method used for purification. All reconstituted vesicle preparations were similar in preferential orientation of acetylcholine receptor toward the external surface, dose-response to carbamylcholine, carbamylcholine-induced desensitization, and carbamycholine-induced influx of 22Na+ per mol of receptor. Carbamylcholine-induced 22Na+ influx/receptor was greater after reconstitution than in native vesicles. This was because, in native vesicles, carbamylcholine induced 22Na+ influx was limited by equilibration of the internal volume of the vesicles with the external 22Na+ concentration, whereas in reconstituted vesicles 22Na+ influx was limited by desensitization of the receptor molecule. We demonstrate that only one of the two toxin binding sites on the receptor monomer, the one which can be affinity alkylated with 4-(N maleimido)benzyltrimethylammonium, controls the carbamylcholine-induced opening of the cation channel. PMID- 6251054 TI - Phosphorylation of the beta subunit of Na+K+-ATPase in Ehrlich ascites tumor by a membrane-bound protein kinase. AB - We have shown previously that proteoliposomes reconstituted with purified Na+K+ ATPase from Ehrlich ascites tumor cells, transport Na+ with low efficiency (Spector, M., O'Neal, S. and Racker, E. (1980) J. Biol. Chem., 255, 5504-5507). We now present evidence that this low efficiency (expressed in the ratio of Na+ transported/ATP-hydrolyzed) is caused by the phosphorylation of the beta subunit of the Na+K+-ATPase by an endogenous protein kinase. On addition of [gamma 32P]ATP, crude tumor plasma membrane preparations phosphorylated the beta subunit of the ATPase, whereas crude mouse brain plasma membranes did not. However, solubilized Na+K+-ATPase from either tumor or brain wre phosphorylated by purified protein kinase from the tumor plasma membrane and dephosphorylated by a phosphatase. In both cases, the phosphorylated enzyme was inefficient; the dephosphorylated enzyme was efficient after reconstitution into liposomes. During isolation of the Na+K+-ATPase from Ehrlich ascites tumor or mouse brain, an endogenous protease partially cleaved from the beta subunit a polypeptide of 29,000 daltons that contained the phosphorylation site. The proteolytic cleavage of the beta subunit was partially inhibited by phenylmethylsulfonyl fluoride and the major site of phosphorylation was then seen in the 53,000-dalton beta subunit of the enzyme. The isolated 29,000-dalton polypeptide from mouse brain ATPase was phosphorylated by tumor protein kinase with a stoichiometry of 1 mol of phosphate/mol of protein. When this 29,000-dalton polypeptide from mouse brain was incorporated into the tumor Na+K+-ATPase after mild proteolytic digestion, a marked increase in efficiency was observed after reconstitution of the Na+ pump. PMID- 6251055 TI - Type Ib glycogen storage disease is caused by a defect in the glucose-6-phosphate translocase of the microsomal glucose-6-phosphatase system. PMID- 6251056 TI - Identification of a rat liver alpha-N-acetylglucosaminyl phosphodiesterase capable of removing "blocking" alpha-N-acetylglucosamine residues from phosphorylated high mannose oligosaccharides of lysosomal enzymes. AB - We recently reported that the high mannose-type oligosaccharides of the biosynthetic intermediates of beta-glucuronidase contain phosphate groups in diester linkage between mannose residues and outer alpha-linked N acetylglucosamine residues (Tabas, I., and Kornfeld, S. (1980) J. Biol. Chem. 255, 6633-6639). We now describe an alpha-N-acetylglucosaminyl phosphodiesterase from rat liver that is capable of removing the N-acetyl-glucosamine residues, leaving phosphomonoester groups on the high mannose oligosaccharide units. This activity is greatly enriched in smooth membrane preparations. It can be distinguished from a lysosomal alpha-N-acetylglucosaminidase by several criteria, including subcellular localization and differential inhibition by amino sugars. In addition, human fibroblasts with mutations which lead to a deficiency of the lysosomal activity have normal levels of the alpha-N-acetylglucosaminyl phosphodiesterase. This enzyme may be involved in the "unmasking" of the phosphomannosyl recognition marker on newly synthesized acid hydrolases which could then direct the targeting of these enzymes to lysosomes. PMID- 6251057 TI - EPR study of heme x NO complexes of ascorbic acid-reduced Pseudomonas cytochrome oxidase and corresponding model complexes. AB - The EPR spectra of the NO complexes of frozen solutions of ascorbic acid-reduced cytochrome oxidase (nitrite reductase) purified from Pseudomonas aeruginosa, of its heme d1-depleted form, and of heme d1 in solutions containing various nitrogenous bases are quite similar to each other as well as to several heme (iron protoporphyrin IX)-containing proteins. The NO complexes of heme d1 (an iron-chlorin) in the presence of nitrogenous bases belong to spectral type C according to Kon's classification and, thus, the energy levels of the iron are closely related to thorse of heme complexes recorded under similar conditions. Comparison of these spectra with those of complexes of known structure suggests that both heme c and heme d1 are linked with Pseudomonas cytochrome oxidase by means of a nitrogenous ligand. The EPR spectrum of the NO complex of the native enzyme exhibits a lack of resolution of the high field (gy) resonance which can be characterized in terms of a spectral contribution from both the heme c and heme d1 moieties. The similarity between the EPR spectra of the NO complexes of horse heart cytochrome c and the heme d1-depleted Pseudomonas cytochrome oxidase before and after interaction with urea suggests structural similarities involving the heme irons. The changes caused by urea are likely to be a breaking or distortion of the bond between the iron and the protein-donated nitrogenous ligand and are similar to alterations seen with NO complexes of hemoglobin under a variety of conditions. PMID- 6251058 TI - Covalent modification of an adenosine 3':5'-monophosphate binding site of the regulatory subunit of cAMP-dependent protein kinase II with 8-azidoadenosine 3':5'-monophosphate. Identification of a single modified tyrosine residue. AB - The regulatory subunit of cAMP-dependent protein kinase II (RII) from porcine heart was modified specifically and covalently using the photoaffinity reagent, 8 azidoadenosine 3':5'-monophosphate (8-N3cAMP). In the presence of excess cAMP, the photo-dependent incorporation of 8-N3cAMP was abolished whereas excess AMP and ATP had no effect. A maximum incorporation of 0.5 mol of 8-N3cAMP was achieved/mol of regulatory subunit monomer (Mr = 55,000). This level of incorporation was obtained when the purified regulatory subunit was treated with urea prior to labeling to remove residual bound cAMP. When the regulatory subunit was labeled with radioactive 8-N3cAMP, cleaved with trypsin, and the tryptic peptides mapped in two dimensions, a single major radioactive peptide was observed. Chemical cleavage of the radioactively labeled RII with cyanogen bromide and subsequent chromatography on Sephadex G-50 also yielded a single major peak of radioactivity. The covalently modified cyanogen bromide peptide subsequently was purified to homogeneity using high performance liquid chromatography. Greater than 90% of the radioactivity that was incorporated into the regulatory subunit was recovered in this cyanogen bromide peptide which had the following sequence: Lys-Arg-Asn-Ile-Ser-His-Tyr (cAMP)-Glu-Glu-Cln-Leu-Val Lys-Hse. When the Edman degradation of this peptide was carried out, the radioactivity derived from the 8-N3cAMP was released with the tyrosine residue at Step 7 identifying this residue as the specific site of attachment of the photoaffinity reagent. PMID- 6251059 TI - Regulation of phosphoenolpyruvate carboxykinase (GTP) mRNA turnover in rat liver. PMID- 6251060 TI - Characterization of yeast iso-1-cytochrome c mRNA. AB - The iso-1-cytochrome c mRNA has been identified by hybridization of a 32P probe prepared from a plasmid containing the iso-1-cytochrome c gene to RNA size fractionated on agarose gels and transferred to paper. A hybridization band was visible with RNA prepared from wild type cells, but not with RNA prepared from an iso-1-cytochrome c deletion mutant. RNA prepared from cells containing a nonsense mutation in the iso-1-cytochrome c gene showed reduced levels of hybridization. The RNA that hybridized to the probe was 700 +/- 50 nucleotides in length and was polyadenylated. The cellular levels of this RNA were repressed by glucose, and this repression was achieved within 5 min after glucose addition to a derepressed culture. No precursors of this RNA were detected in wild type cells or in an RNA1 mutant, temperature-sensitive for RNA metabolism. The length of the 3' noncoding region of this RNA was determined to be 200 +/- 25 nucleotides (excluding the poly(A) tail) and the 5' noncoding region was estimated to be about 120 nucleotides in length. PMID- 6251061 TI - Structure of the rat prolactin gene. AB - The organization and sequence of the rat preprolactin gene has been investigated. Analysis of two different plasmids containing pituitary cDNA inserts has provided the complete 681-nucleotide coding sequence of preprolactin as well as 17 nucleotides preceding the initiation codon and 90 nucleotides following the termination codon. Digestion of rat chromosomal DNA with the restriction endonuclease Eco RI followed by size fractionation and hybridization to a labeled prolactin cDNA probe has demonstrated that prolactin genomic sequences are located on 6.0-, 3.9-, and 2.9-kilobase fragments. The 6.0- and 3.9-kilobase fragments were isolated from a library of cloned rat DNA fragments. The sequence of more than 1800 nucleotides of the cloned DNA has been determined. The sequenced region contains coding regions of 180 and 189 nucleotides which specify the COOH-terminal 123 amino acids of the 227-amino-acid sequence of rat preprolactin. These coding regions are separated by an intervening sequence of 597 nucleotides. At least one other large intervening sequence separates this region from the region coding for the NH2-terminal portion of preprolactin. Hybridization experiments suggested that the intervening sequences of the rat prolactin gene contain DNA sequences which are repeated elsewhere in the rat genome. PMID- 6251062 TI - Smooth microsomes. a trap for cholesteryl ester formed in hepatic microsomes. AB - Acyl-CoA:cholesterol acyltransferase was found predominantly (85%) in RNA-rich microsomes, the rest being in RNA-poor and smooth microsomes. However, the esterified cholesterol concentration of smooth microsomes was 2-fold greater than that of RNA-rich microsomes, suggesting the possibility of an interaction between RNA-rich and smooth microsomes. The distribution of cholesteryl ester between microsome subfractions was examined after incubation of a mixture of RNA-rich and smooth microsomes with [1-14C]palmitoyl-CoA. Based upon specific acyl CoA:cholesterol acyltransferase activities of the individual fractions, only 31 +/- 3% of the total cholesteryl ester radioactivity should have been found in the smooth component. However, the smooth microsomes contained 54 +/- 3% (p < 0.01) of the radioactive cholesteryl esters. The entrapment of radioactive cholesteryl ester in the smooth microsomes could not be accounted for by passive transfer of cholesteryl ester from RNA-rich microsomes to smooth microsomes. It is proposed that cholesterol in the smooth microsomal membranes may have been esterified by acyl-CoA:cholesterol acyltrasferase located on the surface of RNA-rich microsomes with the resulting cholesteryl ester retained in the smooth microsomes. This hypothesis was strengthened by the observation that acyl-CoA:cholesterol acyl transferase was located on the cytoplasmic surface of the RNA-rich microsomal vesicle. PMID- 6251063 TI - Liver cell adenylate cyclase and beta-adrenergic receptors. Increased beta adrenergic receptor number and responsiveness in the hypothyroid rat. PMID- 6251064 TI - Glycosaminoglycans and other carbohydrate groups bound to proteins of control and transformed cells. AB - The membrane glycoproteins from control (BHK21/C13) and Rous sarcoma virus transformed (C13/B4) baby hamster kidney cells labeled with D-[14C]- or D [3H]glucosamine, respectively, were purified by means of polyacrylamide electrophoresis and gel electrofocusing. The homogeneity of the isolated glycoproteins was demonstrated by analysis of the NH2-terminal peptides. Some purified glycoproteins were found to be hybrid molecules in terms of the type of oligosaccharides they bear. The majority of the oligosaccharides (approximately 90%) bound on thee glycoproteins are N-glycosidically linked (Mr approximately 3000 to 5000). Another 5% appears to be small groups linked O-glycosidically to several adjacent or closely spaced amino acid residues. The remainder (5%) of the carbohydrate groups appears to be small, covalently bound glycosaminoglycans. This is the first report of hybrid molecules bearing glycosaminoglycans in the cell surface. The ratio of the types of oligosaccharides varies among different glycoproteins. There is slightly more glycosaminoglycan present on glycoproteins from malignant cells. A remarkably complex but similar array of N-glyucosidically linked oligosccharides is bound to different individual membrane glycoproteins. Each individual polypeptide must contain only a small number of the total observed carbohydrate groups, i.e. the carbohydrate groups on individual polypeptides are grossly heterogeneous. This implies that purification is based largely on the characteristics of the polypeptide, and that overall charge and size of the carbohydrate groups are relatively constant in a single population of glycoproteins. Our results suggest that the differences between the carbohydrate groups derived from glycoproteins from control and transformed cells are mainly quantitative. PMID- 6251065 TI - Vitamin K3 (menadione) and related quinones, like tumor-promoting phorbol esters, alter the affinity of epidermal growth factor for its membrane receptors. AB - The effects of vitamin K3, quinones, fat-soluble vitamins, and various naturally occurring and synthetic compounds on the binding of 125I-epidermal growth factor (EGF) to mink lung cells or murine 3T3 cells in culture were studied. Vitamin K3, but not other fat-soluble vitamins, markeldy inhibits the binding of 125I-labeled EGF to treated cells, but does not affect the binding of insulin, concanavalin A, alpha-2-macroglobulin, and murine leukemia virus glycoprotein, gp70, to their membrane receptors. The binding of multiplication stimulating activity to treated cells is also reduced to some extent. Vitamin K3 alters the affinity of the receptors for EGF without changing the total number of available receptors per cell. Vitamin K3 modulation of EGF-receptor interaction is a temperature- and time-dependent phenomenon. EGF-receptor interaction is also significantly modulated by 1,4-naphthoquinone, 1,4-benzoquinone, and phenanthrenequinone but not by other quinones of anthracyclic antibiotics. PMID- 6251066 TI - Lactose and D-galactose metabolism in Staphylococcus aureus. III. Purification and properties of D-tagatose-6-phosphate kinase. AB - D-Tagatose-6-phosphate kinase, an inducible enzyme that functions in the metabolism of lactose and D-galactose in Staphylococcus aureus, was purified about 300-fold from an extract of D-galactose-grown cells. The enzyme catalyzed the nucleoside triphosphate-dependent phosphorylation of both D-tagatose 6 phosphate and D-fructose 6-phosphate. Although the Vmax values were equal for these two substrates, the apparent Km values differed by 10,000-fold, being 16 micro M for D-tagatose 6-phosphate and 150 mM for D-fructose 6-phosphate. The purified enzyme was free from the constitutive D-fructose-6-phosphate kinase. Phosphoryl donors used by D-tagatose-6-phosphate kinse, listed in order of decreasing rates at saturating concentrations were GTP, UTP ITP ATP, CTP, and TTP; the Km values were 0.38, 0.91, 0.17, 0.16, 18, and 20 mM, respectively. The enzyme appeared to be nonallosteric; it exhibited Michaelis-Menten kinetics and was not inhibited by high concentrations of MgATP. However, it was activated 3- to 4-fold by 33.3 mM K+, NH4+, Rb+, and Cs+, and was inhibited 31 to 65% by 33.3 mM Na+ and Li+. It was inactivated reversibly by the thiol reagent, N ethylmaleimide. The subunit molecular weight was estimated to be 52,000, and the native enzyme appeared to be a dimer with a sedimentation coefficient of 6.8 S. Data on stability, pH optimum, and inducibility of the enzyme are also presented. PMID- 6251067 TI - Specificity of promoter site utilization in vitro by bacterial RNA polymerases on Bacillus phage phi 29 DNA. Transcription mapping with exonuclease III. AB - Bacillus subtilis RNA polymerase holoenzyme transcribes phi 29 DNA in vitro producing five major RNA species defined by characteristic electrophoretic mobilities. In addition to these products, Escherichia coli RNA polymerase transcribes phi 29 DNA to yield three RNA species not detected when transcribing with the B. subtilis enzyme under the same optimal reaction conditions for RNA synthesis. Transcriptional analysis of purified restriction fragments and exonuclease III-digested DNA established locations of six promoter and three termination sites defining the eight transcripts. The transcription map shows that E. coli RNA polymerase initiates transcription at three sites not efficiently utilized by the B. subtilis enzyme. However, initiation by the B. subtilis polymerase from at least two of these sites could be detected at E:DNA ratios greater than 10 in the absence of competing promoters. These results indicate that differences between the two polymerases in promoter utilization are not explained by specificity of promoter binding, but represent differences in responding to promoter strength. Transcription of phi 29 DNA and T7 DNA by E. coli core polymerase with either B. subtilis or E. coli sigma subunits results in formation of transcripts identical with those produced by E. coli holoenzyme, suggesting that core polymerase contains elements important in determining relative promoter strength. The efficiency of rifampicin-resistant complex formation on phi 29 and T7 promoters is also dependent upon the source of core polymerase. PMID- 6251068 TI - Kinetic intermediates in the formation of ordered complexes from cytochrome c fragments. Evidence that methionine ligation is a late event in the folding process. AB - The reactions of ferric heme-containing fragments with apofragments to form ordered complexes resembling native horse heart cytochrome c have been studied under conditions which resolve the overall process into consecutive second order and first order kinetic steps. In the initial, second order step the two fragments combine to form an intermediate complex which exhibits tryptophan 59 fluorescence quenching similar to native cytochrome c, but which has not yet achieved the native ligation state of the heme iron. The existence of first order processes following the second order step is demonstrated by absorbance changes in the Soret region. the entire absorbance change at 695 nm, relating to ligation of the sulfur atom of methionine 80 to the heme iron, is also associated with these first order processes. Thus, ligation of methionine is a late event in this self ordering of the polypeptide chains. Since the conformational energy is assumed to distinctly decrease in this late process of folding (Parr, G.R., and Taniuchi, H. (1980) J. Biol. Chem. 255, 2616-2623), it would follow that small spatial rearrangements of the polypeptide chains in the late stage of folding (as manifested by the ligation of methionine) are associated with a specific decrease in energy. PMID- 6251069 TI - Structure of a newly isolated variant of Simian virus 40 DNA containing monkey DNA and its similarity to previously isolated variants. AB - The structure of a newly and independently isolated defective variant of simian virus 40 that contains covalently linked monkey and SV40 DNA sequences is described. This variant, termed 290, has a structure essentially identical with a previously isolated and characterized variant named CVP8/1/P2 (Eco RI res). The structural similarities include the monkey (host) DNA segment that is combined with viral DNA sequences, the particular viral DNA segment that is present, and the arrangement of these within the defective genome. The monkey DNA segment contains sequences derived from both low and high reiteration frequency monkey DNA. The viral sequences include the origin of replication. The separate isolation of essentially identical variants suggests a high level of specificity in the events leading to the formation and amplification of this type of defective genome. PMID- 6251070 TI - Cloning of fragments of lambda dapB2 DNA and identification of the dapB gene product. AB - DNA of the specialized transducing phage lambda dapB2 has been digested with the restriction endonucleases Bam I, HindIII, or both together to generate fragments originating from the bacterial substitution on the phage. Seven such fragments ranging in size from 0.8 to 7.1 kilobases and encompassing the entire bacterial substitution of 18 kilobases of DNA have been covalently ligated to the vector pBR322. The recombinant plasmids so constructed have been tested for their ability to complement the dapB17 allele in Escherichia coli strain AT999. Only pGM4, which contains a 7.1 kilboase fragment generated by Bam I cleavage of lambdadapB2 inserted into pBR322, relieves this strain's requirement for DL diaminopimelic acid and restores dihyrodipicolinic acid reductase activity to wild type levels. Deletions were obtained in pGM4 by two methods. None of the resultant shortened plasmids were proficient in complementation of the dapB17 allele. The proteins encoded by the parental plasmid and by those of seven deletions derived from it have been identified by coupled transcription and translation of plasmid DNA templates in vitro or by the stimulation of protein synthesis promoted by these plasmids in an ultraviolet irradiated host. The parent encodes four proteins unique to the 7.1 kilobase insert whose apparent molecular weights are 48,000, 36,000, 32,000, and 17,000. Of these, the protein of 32,000 is consistently missing when noncomplementing pasmids harboring deletions are used as templates. This protein is tentatively identified as the product of the dapB gene. The role of the other three proteins whose genes are closey linked to the dapB gene is unknown. There appear to be at least two transcriptional units within this cluster of genes, however, suggesting independent regulation and, possibly, function. PMID- 6251071 TI - A specific DNA unwinding activity associated with SV40 large T antigen. AB - The incubation of highly purified large T antigen with relaxed, circular SV40 DNA in the presence of topoisomerase I (nicking closing enzyme) resulted in the introduction of negative superhelical turns in the DNA. ATP was not required for this reaction. A similar introduction of superhelical turns could also be obtained when a recombinant plasmid DNA (Y182), which contains sequences from both SV40 DNA and pBR322, was used. However, no effect was observed when relaxed pBR322 DNA, which does not contain SV40 DNA sequences, was incubated with T antigen in the presence of topoisomerase. These results are consistent with the hypothesis that large T antigen can recognize and unwind specific sequences on SV40 DNA. PMID- 6251072 TI - Activation of phospholipid methyltransferase by glucagon in rat hepatocytes. AB - Glucagon produces a time- and dose-dependent activation of phospholipid methyltransferase activity in isolated rat hepatocytes. Half-maximal effect is caused by a dose of glucagon of 1 x 10(-10) M. This activation is due to an increase of the Vmax value of the enzyme, without affecting the Km value for S adenosylmethionine. Exogenous cyclic AMP added to isolated rat hepatocytes mimics the effect of glucagon, and the activation of phospholipid methyltransferase by a nonsaturating concentration of glucagon is spontaneously reversible within 40 min of incubation. PMID- 6251073 TI - Budding of Rous sarcoma virus and vesicular stomatitis virus from localized lipid regions in the plasma membrane of chicken embryo fibroblasts. AB - The origin of the envelope lipids acquired by Rous sarcoma virus (RSV) and vesicular stomatitis virus (VSV) during budding from the plasma membrane of chicken embryo fibroblasts was examined. Several differences were observed between the lipid composition of RSV and the plasma membrane. When the phospholipid composition of the cells was modified by growing them in the presence of the choline analogues, N,N-dimethylethanolamine or l-2-amino-1 butanol, the phospholipid composition of the virus was subsequently altered but in a very different manner than the plasma membrane. In the plasma membrane, the increase in the analogue-containing phospholipid was at the expense of phosphatidylcholine and phosphatidylethanolamine while the amount of sphingomyelin remained constant. In RSV, however, there was a decrease in sphingomyelin and phosphatidylethanolamine while there was only a small change in the amount of phosphatidylcholine. Phospholipid polar head group modification did not significantly alter the fatty acid composition or the cholesterol content. Membranes of phagosomes isolated after the cells had ingested latex beads had essentially the same phospholipid composition as the plasma membrane. The phospholipid composition of VSV was different from RSV, but it also did not reflect the composition of the plasma membrane. The composition of the plasma membrane was intermediate between the viruses and the endoplasmic reticulum, but contamination of the plasma membrane fraction with the endoplasmic reticulum could not account for the observed differences. These results show that the viruses bud from localized lipid regions that do not reflect the average properties of the plasma membrane. PMID- 6251074 TI - Assembly of the mitochondrial membrane system. Sequences of yeast mitochondrial tRNA genes. AB - Two cytoplasmic "petite" (rho-) clones of Saccharomyces cerevisiae have been selected for the retention of the aspartic acid tRNA gene. The two clones, designated DS200/A102 and DS200/A5, have tandemly repeated segments of mitochondrial DNA (mtDNA) with unit lengths of 1,000 and 6,400 base pairs, respectively. The DS200/A102 genome has a single tRNA gene with a 3'-CUG-5' anticodon capable of recognizing the 5'-GAC-3' and 5'-GAU-3' codons for aspartic acid. The mtDNA segment of DS200/A102 has been determined to represent the wild type sequence from 5.3 to 6.8 map units. The genome of DS200/A5 is more complex encompassing the region of wild type mtDNA from 3.5 to 12.7 units. A continuous sequence has been obtained from 3.5 to 8.6 units. In addition to the aspartic acid tRNA, this region codes for the tRNAUGCAla,tRNAUCUArg, tRNAACGArg, tRNAGCUSer,tRNAUCCGly and tRNAUUULys. The DNA sequence of the DS200/A5 genome has allowed us to deduce the secondary structures of the seven tRNAs and to assign precise map positions for their genes. All the tRNAs except tRNA GUCAsp exhibit most of the invariant features of prokaryotic and eukaryotic tRNAs. The aspartic acid tRNA has unusual D and T psi C loops. The structure of this tRNA is similar to the mitochondrial initiator tRNA of Neurospora crassa (Heckman, J.E., Hecker, L.I., Shwartzbach, S.D., Barnett, W.E., Baumstark, B., and RajBhandary, U.L. Cell 13, 83-95). PMID- 6251075 TI - S-Adenosylmethionine synthetase from Escherichia coli. AB - Adenosylmethionine (AdoMet) synthetase has been purified to homogeneity from Escherichia coli. For this purification, a strain of E. coli which was derepressed for AdoMet synthetase and which harbors a plasmid containing the structural gene for AdoMet synthetase was constructed. This strain produces 80 fold more AdoMet synthetase than a wild type E. coli. AdoMet synthetase has a molecular weight of 180,000 and is composed of four identical subunits. In addition to the synthetase reaction, the purified enzyme catalyzes a tripolyphosphatase reaction that is stimulated by AdoMet. Both enzymatic activities require a divalent metal ion and are markedly stimulated by certain monovalent cations. AdoMet synthesis also takes place if adenyl-5'yl imidodiphosphate (AMP-PNP) is substituted for ATP. The imidotriphosphate (PPNP) formed is not hydrolyzed, permitting dissociation of AdoMet formation from tripolyphosphate cleavage. An enzyme complex is formed which contains one equivalent (per subunit) of adenosylmethionine, monovalent cation, imidotriphosphate, and presumably divalent cation(s). The rate of product dissociation from this complex is 3 orders of magnitude slower than the rate of AdoMet formation from ATP. Studies with the phosphorothioate derivatives of ATP (ATP alpha S and ATP beta S) in the presence of Mg2+, Mn2+, or Co2+ indicate that a divalent ion is bound to the nucleotide during the reaction and provide information on the stereochemistry of the metal-nucleotide binding site. PMID- 6251076 TI - Properties of acyl-CoA:cholesterol acyltransferase in rat liver microsomes. Topological localization and effects of detergents, albumin, and polar steroids. PMID- 6251077 TI - Purification and characterization of nuclease beta from Ustilago maydis. AB - A nuclease highly active on single-stranded DNA has been purified 11,200-fold from Ustilago maydis. The enzyme has a sedimentation coefficient of 4.3 S and a Stokes radius of 36 A. The native form of the enzyme appears to be a single polypeptide chain of 68,000 daltons. The enzyme is fully active in the presence of chelating agents but is strongly inhibited by nucleotides. Maximal activity is seen at pH 6. The enzyme hydrolyzes linear DNA in an exonucleotytic fashion from the 5' end liberating 3'-mononucleotides and small oligonucleotides. Degradation of DNA takes place through a distributive mode rather than a processive mode. The enzyme is also active on both single-stranded and duplex circular DNA, dephosphorylates 5'-nucleotides, and hydrolyzes RNA. PMID- 6251078 TI - Acetylglutamate kinase. A mitochondrial feedback-sensitive enzyme of arginine biosynthesis in Neurospora crassa. AB - The radioisotopic method used to assay acetylglutamate kinase (EC 2.7.2.8) of Neurospora crassa has been shown to detect two distinct enzymatically catalyzed reactions. The enzymes were separated by differential centrifugation into a cytosolic activity and an organellar activity. Both activities required ATP and were thermal-labile. The cytosolic activity was insensitive to inhibition by arginine and formed a stable reaction product in the absence of hydroxylamine. The organellar activity had an absolute requirement for hydroxylamine in order to form a stable reaction product. The product of the cytosolic activity was separated from acetylglutamate hydroxamate (the product of the organellar activity) and was identified as the cyclic amide pyroglutamate by cation exchange chromatography. The organellar activity has been implicated in arginine biosynthesis by the following criteria: it was completely and specifically inhibited by arginine concentrations as low as 200 microM; its level was elevated 2-fold in a mutant strain with derepressed levels of arginine biosynthetic enzymes; and it was absent in an arginine auxotrophic strain (the cytosolic activity was present). The organellar activity co-sedimented with mitochondria during isopycnic gradient centrifugation. The metabolic problems posed by a mitochondrial location of a feedback-sensitive enzyme and the cytosolic location of its effector are discussed. PMID- 6251079 TI - Demonstration of two classes of opiate binding sites in the nervous tissue of the marine mollusc Mytilus edulis. Positive homotropic cooperativity of lower affinity binding sites. PMID- 6251080 TI - Subcellular localization of sugar nucleotide synthetases. PMID- 6251081 TI - Biochemical characterization of the tsE1 mutant of vesicular stomatitis virus (New Jersey). Alterations in the NS protein. AB - Alterations in the NS protein of the tsE1 mutant of vesicular stomatitis virus (New Jersey serotype) appear to be responsible for its temperature-sensitive phenotype. The NS proteins of thermostable revertants of tsE1 migrated in polyacrylamide gels containing sodium dodecyl sulfate with apparent sizes which were identical to tsE1 NS, or which were 5% or 14% larger than tsE1 NS. These novel differences persisted during electrophoresis in 10% and 12.5% acrylamide gels, and in gels with gradients of acrylamide, suggesting that aberrant sodium dodecyl sulfate binding was not involved. Co-infection of cells with pairs of viruses resulted in the synthesis of both types of NS protein, suggesting that no trans-acting phenomenon was involved. Two-dimensional gel electrophoresis demonstrated that each of the NS proteins consisted of several species, but the isoelectric points of the proteins from different viruses overlapped. Furthermore, all of the NS species from a particular virus migrated with the same apparent molecular weight, suggesting that aberrant phosphorylation was not responsible for the apparent differences in size. Finally, tryptic peptide maps of amino acid and 32Pi-labeled NS proteins demonstrated that the revertant NS proteins contained all of the peptides and phosphopeptides of tsE1 NS, but each revertant NS with an apparently larger protein also contained an extra nonphosphorylated peptide. These data are consistent with the idea that the reversion of the temperature-sensitive phenotype of tsE1 can be accompanied by production of a significantly larger NS protein. PMID- 6251082 TI - The pH and temperature dependence of the activity of the high Km cyclic nucleotide phosphodiesterase of bakers' yeast. AB - The hydrolysis of adenosine 3':5'-monophosphate by the high Km cyclic nucleotide phosphodiesterase of bakers' yeast was studied over a range of temperature and pH at I = 0.17. The effects of ionic strength and MgCl2 concentration were studied at pH 7.7 and 30 degrees C. Km and Vmax were insensitive to changes in the MgCl2 concentration between 1 and 30 mM, implying that this enzyme (which does not require free divalent metal ions) does not discriminate between free cyclic AMP- and the Mg-cyclic AMP+ complex. Vmax decreased below pH 6.8 because of protonation of a group required in the basic form in the enzyme x substrate complex. On the basis of its pK (5.46 at 30 degrees C) and delta H (23 kJ/mol) this group was tentatively identified as imidazole. Vmax/Km decreased above pH 6.8 because of ionization of a group required in the acid form in the free enzyme, with a pK of 7.88 at 30 degrees C and a delta H of about 13 kJ/mol. Several possibilities exist for the identity of this group, the most likely being a second imidazole, sulfhydryl, or a water molecule bonded to tightly bound zinc. At pH 7.90, log Vmax and log Km both changed linearly with 1/T (between 12 degrees C and 37 degrees C) with enthalpies of 47 and 55 kJ/mol, respectively. Consequently, at low enough cyclic AMP concentration, the rate of reaction at pH 7.90 decreases slightly when the temperature is increased. This is also true at higher pH, but in the physiological pH range (6.4 to 7.5) Vmax/Km and, therefore, the rate of reaction at very low cyclic AMP concentration were nearly independent of temperature. Under physiological conditions, the Km approaches the upper limit of in vivo cyclic AMP concentrations in yeast, and at normal in vivo cyclic AMP concentrations the pH optimum is within or below the physiological range of pH in yeast. PMID- 6251083 TI - Chicken globin genes. Nucleotide sequence of cDNA clones coding for the alpha globin expressed during hemolytic anemia. PMID- 6251084 TI - Sequestration of 125I-labeled beta nerve growth factor by sympathetic neurons. AB - Nerve growth factor binds to cell surface membrane receptors on sensory and sympathetic neurons. The binding of radiolabeled beta nerve growth factor to sympathetic neurons is characterized by two specific binding sites with similar dissociation constants to those seen for sensory neurons. The high affinity site, type I, has an apparent dissociation constant of 1.1 X 10(-11) M. The lower affinity site, type II, has an apparent dissociation constnat of 5.0 X 10(-10) M. When radiolabeled beta nerve growth factor is incubated with sympathetic nerve cells for various lengths of time, as much as 50% of the specifically bound labeled nerve growth factor is sequestered. Sequestration is time- and energy dependent, and appears to o ccur mainly through type I sites. These data suggest a step which is subsequent to the binding of nerve growth factor to its responsive cells and may be the first step in the process that allows nerve growth factor to be internalized. PMID- 6251085 TI - The forms of tRNATrp found in avian sarcoma virus and uninfected chicken cells have structural identity but functional distinctions. AB - We have determined the complete nucleotide sequence of the avian tRNATrp which serves as primer for avian retrovirus DNA synthesis by the viral polymerase. The sequence is identical to that reported for tRNATrp present in uninfected avian cells (Harada, F., Sawyer, R. C., and Dahlberg, J. E. (1975) J. Biol. Chem. 250, 3487-3497). Although there appears to be only a single species of tRNATrp in avian cells, two functionally different forms within the population can be distinguished. We show that the tRNATrp isolated from virions can act in vitro as an efficient suppressor for UGA. The suppressor activity is roughly 3-fold greater with viral tRNATrp than with cellular tRNATrp. In addition, it has been reported (Panet, A., Haseltine, W. A., Baltimore, D., Peters, G., Harada, F., and Dahlberg, J. E. (1975) Proc. Natl. Acad. Sci. U. S. A. 72, 2535-2539) that the viral polymerase can bind 100% of viral tRNATrp, but only 30% of cellular tRNATrp. Hence, avian retroviruses seem to selectively incorporate and utilize only one of these forms. Since the nucleotide sequence and nucleoside modifications are identical between viral and cellular tRNATrp, two conformations of avian tRNATrp may exist which can influence several biological activities of the molecule. PMID- 6251086 TI - Studies on the phosphorylation of the type I cAMP-dependent protein kinase. AB - The regulatory subunit of the type I cAMP-dependent protein kinase (RI) can be separated into multiple forms on isoelectric focusing gels. RI from bovine skeletal muscle gives rise to bands at pI = 5.57 and 5.45. Phosphate determinations indicate that the more acidic band contains protein-bound phosphate. RI from rat skeletal muscle can be separated into three bands of pI = 5.57, 5.45, and 5.35. The two acidic forms comigrate with labeled RI isolated from rat soleus muscles that were incubated with [32P]orthophosphate. RI from bovine muscle is isolated mainly in the unphosphorylated state while that from rat muscle is primarily phosphorylated. At lest 4 mol of phosphate can be incorporated into each RI dimer following extensive phosphorylation by cGMP dependent protein kinase in vitro. Two phosphopeptides are observed on polyacrylamide gels following partial proteolysis of in vitro phosphorylated rat RI. One of these peptides is also observed following proteolysis of rat RI phosphorylated in intact soleus muscles. PMID- 6251088 TI - Purification, subunit structure, and serologicai analysis of calf thymus ribonuclease H I. AB - Calf thymus ribonuclease H I (for nomenclature, see Busen, W., and Hausen, P. (1975) Eur. J. Biochem. 52, 179-190) has been purified to near homogeneity. The large scale purification procedure results in a 1,000-fold enrichment of enzyme protein over the crude extract. The enzyme has a molecular weight of about 80,000, and S value of about 5, and an isoelectric point of about 4.9 under nondenaturing conditions. The purified enzyme sample contains two forms of ribonuclease H I, possibly isozymes, named ribonuclease H I 1 and ribonuclease H I 2. They can be activated by Mn2+ or Mg2+ ions. The most highly purified fraction is composed of four polypeptides named A, B, C, and D with molecular weights of 31,6000, 26,6000, 24,800, and 24,300, respectively. Polypeptides A, C, and D are acidic, whereas Polypeptide B is basic. Each form consists of three polypeptides. Ribonuclease H I 1 and ribonuclease H I 2 have Polypeptides A and B in common and differ from each other in the third. The data are consistent with a trimeric (A, B, C/D) or tetrameric (A, B2, C/D) structure for calf thymus ribonuclease H I. When alkalisensitive supercoiled DNA molecules containing ribonucleotides covalently inserted in one of the DNA strands are used as substrate, the products of the reaction are relaxed circles; thus, ribonuclease H I has an endonucleolytic mode of action. The final preparation is free of ribonuclease, and also of endodeoxyribonuclease activity single- and double stranded DNA. Rabbit antiserum raised against the most highly purified calf thymus ribonuclease H I specifically precipitates the Polypeptides A, B, C, and D and inhibits the Mn2+ - and Mg2+ -dependent enzyme activities to more than 90%. Whereas a typical monophasic neutralization curve is obtained with Mn2+ activation, the neutralization curve observed with Mg2+ is biphasic. These results and several other differences between the Mn2+ - and the Mg2+ -dependent activities of the ribonucleases H I seem best explained by a hypothesis in which the enzymes exist in two different conformations depending on the type of divalent cation activation. The antiserum neutralizes ribonuclease H I but not the other known calf thymus ribonuclease H activities (IIa; IIb), demonstrating that the different ribonuclease H activities in calf thymus are serologically distinct. Ribonuclease H I is localized in the cell nucleus as visualized by immunofluorescent staining of bovine cells. PMID- 6251087 TI - Membrane phospholipid synthesis in Escherichia coli. Cloning of a structural gene (plsB) of the sn-glycerol-3-phosphate acyl/transferase. AB - Si+ hybrid ColE1 plasmids of the Clarke-Carbon collection (Clarke, C., and Carbon, J. (1976) Cell 9, 91-99) which eliminate the sn-glycerol 3-phosphate growth requirement of a mutant of Escherichia coli with a Km defect in sn glycerol-3-phosphate acyltransferase (plsB) were identified. Marked overproduction of a plasmid-encoded sn-glycerol-3-phosphate acyltransferase with a wild type Km in a host plsB- background indicates that the hybrid plasmids carry a structural gene for this enzyme. In addition, all of these plasmids suppress the phenotype of a mutation in a second locus involved in phospholipid biosynthesis, dgk (diglyceride kinase), and one of them also bears the dnaB structural gene. Diglyceride kinase activity is also overproduced in these strains. The linkage of plsB, dgk and dnaB loci was confirmed by transduction analysis which demonstrated the clockwise gene order malB, dnaB, dgk, plsB, and uvrA near Minute 91 on the E. coli linkage map. This is in contrast to the previously reported co-transduction of plsB with dctA near Minute 78 (Cronan, J. E., Jr., and Bell, R. M. (1974) J. Bacteriol., 120, 227-233). Recloning of restriction endonuclease fragments and in vitro mutagenesis have localized the dgk, and plsB loci to a 2.2-megadalton DNA segment, and have demonstrated that diglyceride kinase and sn-glycerol-3-phosphate acyltransferase activities reside in separate polypeptides. Availability of these clones and mutationally altered derivatives has allowed the identification of a single polypeptide (Mr = 83,000) corresponding to the sn-glycerol-3-phosphate acyltransferase and purification of this membrane-bound enzyme to near homogeneity (Larson, T. J., Lightner, V. A., Green, P. R., Modrich, P., and Bell, R. M. (1980) J. Biol. Chem. 255, 9421-9426). The size of the plsB polypeptide indicates that a major fraction of the DNA segment to which this gene has been localized is involved in coding for the sn glycerol-3-phosphate acyltransferase. PMID- 6251089 TI - Internal structure of the silk fibroin gene of Bombyx mori. II. Remarkable polymorphism of the organization of crystalline and amorphous coding sequences. AB - Alleles of the silk fibroin locus from 22 inbred stocks of Bombyx mori were compared. Nineteen alleles differing from one another in length and internal sequence organization were distinguished. Individuals from a single stock generaly are homozygous for a particular allele, as judged by their gene restriction pattern and the length of the fibroin protein produced. Restriction with endonucleases having four base recognition sequences revealed no variation with respect to these particular coding sequences among the alleles tested. Furthermore, digestion with endonucleases specific for amorphous coding sequences indicated that all the alleles tested had amorphous coding sequence domains alternating regularly with crystalline domains just as was found for the L allele. The stocks differed considerably in their fibroin length, and in the total length of the fibroin coding regions of their genes. These differences were accounted for by variation in the lengths of crystalline coding domains when compared to the ends of the genes. Several characteristics of the alleles indicates that this variation results from recombination between the highly repetitive coding sequences of misaligned genes (homologous unequal crossing over). Polymorphism of the fibroin gene in B, mori appears to be greater than for any other gene for which data are available. PMID- 6251090 TI - Purification and structural properties of gelsolin, a Ca2+-activated regulatory protein of macrophages. AB - We describe the purification procedure and some of the physiochemical properties of gelsolin, a major Ca2+-dependent regulatory protein of actin gel-sol transformation in rabbit lung macrophages. Gelsolin accounts for the majority of Ca2+ control of actin gelation in macrophage extracts. It is a single polypeptide chain with an average molecular weight of 91,000 a Stokes radius of 44 A, a sedimentation coefficient (s20(0),w) of 4.9 S, an isoelectric point of 6.1, and a frictional ratio of 1.43. Gelsolin binds 2 mol of Ca2+ with high affinity (Ka 1.09 X 10(6) M-1) in the presence of 0.1 M KCl and 2 mM MgCl2. PMID- 6251091 TI - Ca2+ control of actin gelation. Interaction of gelsolin with actin filaments and regulation of actin gelation. AB - We elucidated the mechanism by which gelsolin, a Ca2+-dependent regulatory protein from lung macrophages, controls the network structure of actin filaments. In the presence of micromolar Ca2+, gelsolin bound Ca2+. The Ca2+-gelsolin complex reduced the apparent viscosity and flow birefringence of F-actin and the lengths of actin filaments viewed in the electron microscope. However, concentrations of gelsolin causing these alterations did not effect proportionate changes in the turbidity of actin filament solutions or in the quantity of nonsedimentable actin as determined by a radioassay. From these findings, we conclude that gelsolin shortens actin filaments without net depolymerization. Such an effect on the distribution of actin filament lengths led to the prediction that low concentrations of gelsolin would increase the critical concentration of actin-binding protein required for incipient gelation of actin filaments in the presence of Ca2+, providing an efficient mechanism for controlling actin network structure. We verified the prediction experimentally, and we estimated that the Ca2+-gelsolin complex effectively breaks the bond between actin monomers in filaments with a stoichiometry of 1:1. The effect of Ca2+-gelsolin complex on actin solation was rapid, independent of temperature between 0 degrees and 37 degrees C, and reversed by reducing the free Ca2+ concentration. PMID- 6251092 TI - Transcription and in vitro processing of yeast 5 S rRNA. AB - A method is described for the isolation of a yeast chromatin fraction highly enriched in ribosomal DNA sequences. In the presence of exogenous yeast RNA polymerase III, this purified chromatin actively synthesizes a set of 5 S ribosomal RNAs all of which have 5'-sequences identical with mature 5 S RNA but which end with a variable number (up to 10) of additional residues at the 3' terminus. These extra nucleotides are precisely removed by a processing nuclease found in the chromatin supernatant fraction. PMID- 6251093 TI - Opacity units and opacity-unit mililitres. PMID- 6251094 TI - A two-dose schedule for immunization of infants against diphtheria, pertussis and tetanus. PMID- 6251095 TI - Slipped upper femoral epiphysis after radiotherapy. AB - Eight slipped upper femoral epiphyses in patients who had had radiotherapy are described. These cases involved five patients in an "at risk" population of 48. This increased incidence is highly significant. PMID- 6251096 TI - Ultrastructure of Na,K-transport vesicles reconstituted with purified renal Na,K ATPase. AB - To study the size and structure of the Na,K-pump molecule, the ultrastructure of phospholipid vesicles was examined after incorporation of purified Na,K-ATPase which catalyzes active coupled transport of Na+ and K+ in a ratio close to 3Na/2K. The vesicles were analyzed by thin sectioning and freeze-fracture electron microscopy after reconstitution with different ratios of Na,K-ATPase protein to lipid, and the ultrastructural observations were correlated to the cation transport capacity. The purified Na,K-ATPase reconstituted with phospholipids to form a very uniform population of vesicles. Thin sections of preparations fixed with glutaraldehyde and osmium tetroxide showed vesicles limited by a single membrane which in samples stained with tannic acid appeared triple-layered with a thickness of 70 A. Also, freeze-fracture electron microscopy demonstrated uniform vesicles with diameters in the range of 700-1,100 A and an average value close to 900 A. The vesicle diameter was independent of the amount of protein used for reconstitution. Intramembrane particles appeared only in the vesicle membrane after introduction of Na,K-ATPase and the frequency of intramembrane particles was proportional to the amount of Na,K-ATPase protein used in the reconstitution. The particles were evenly distributed on the inner and the outer leaflet of the vesicle membrane. The diameter of the particles was 90 A and similar to our previous values for the diameter of intramembrane particles in the purified Na,K-ATPase. The capacity for active cation transport in the reconstituted vesicles was proportional to the frequency of intramembrane particles over a range of 0.2-16 particles per vesicle. The data therefore show that active coupled Na,K transport can be carried out by units of Na,K-ATPase which appear as single intramembrane particles with diameters close fo 90 A in the freeze-fracture micrographs. PMID- 6251097 TI - Localization of a 16,000-dalton fragment of the common precursor of adrenocorticotropin and beta-lipotropin in the rat and human pituitary gland. AB - To clearly identify cells and organelles containing the common precursor (31,000 dalton) for both adrenocorticotropin (ACTH) and beta-lipotropin (beta-LPH), an immunohistochemical localization of a fragment (16,000 dalton) of the precursor that is not common to beta-LPH and ACTH was conducted in rat and human pituitary glands. With the help of specific antibodies that do not cross-react with beta LPH and ACTH, the 16,000-dalton fragment was localized in the cells that also produce ACTH and beta-LPH in both the pars distalis and pars intermedia of the rat pituitary. At the electron microscope level, the secretory granules that contain ACTH were also stained for 16,000-dalton fragment. In the human pituitary, the 16,000-dalton fragment was also observed in all the secretory granules of lipocorticotrophs. These results suggest that, after enzymatic cleavage, fragment(s) of the common precursor and/or the whole common precursor remain packaged within the secretory granules with peptides of known activity. PMID- 6251098 TI - Control and virus-transformed baby hamster kidney cells resistant to ethidium bromide. I. Characterization and the respiratory enzymes. AB - Cell lines resistant to ethidium bromide have been developed from cultured mammalian BHK21/C13 cells and these same cells transformed by Rous sarcoma virus (C13/B4). Cells resistant to 2 micrograms ethidium bromide per milliliter have been cloned. One clone of the control and one of the virus-transformed cell lines has been employed for characterization. The resistant cells, in the presence of 2 micrograms ethidium bromide/ml, grow at approximately the same rate as the untreated parental cells. The control cells possess a "normal" karyotype (44 chromosomes), while the corresponding ethidium bromide mutant has a reduced chromosome number of 41 and a number of translocations. The mitochondria displayed morphological alterations compared to the parental lines during the transition phase prior to the isolation of the ethidium bromide-resistant cells. The mitochondria of the ethidium bromide-resistant mutants appear somewhat enlarged with a normal morphology. The effect of ethidium bromide on selected respiratory enzymes in normal and virus-transformed ethidium bromide-resistant baby hamster kidney cells was determined. Ethidium bromide-resistant cells exhibited a depressed level of cytochrome aa3. This depression could not be reversed by growth in ethidium bromide-free media. Ethidium bromide-resistant cells possessed the same cytochrome b, c, and c1 levels per cell as their corresponding parental lines. Purified mitochondria isolated from virus transformed ethidium bromide-resistant cells exhibited a depression in cytochrome oxidase-specific activity, while the ethidium bromide-resistant control cells did not. All cell lines studied showed a depression in NADH-ferricyanide and NADH cytochrome c reductase-specific activities relative to their parental BHK21/C13 cells. No increase was observed in virus-transformed ethidium bromide-resistant cells. Ethidium bromide-resistant control cells exhibited a two-fold increase in oligomycin-insensitive adenosine triphosphatase activity relative to their parental cells. All of the cell lines studied possessed equivalent oligomycin sensitive adenosine triphosphatase-specific activity except for the virus transformed, dye-resistant mutant, whose activity was increased. PMID- 6251099 TI - Expression of SV40 tumor antigen in SV40 transformed teratocarcinoma-derived cell lines. AB - The relative importance of viral tumor antigen expression and the cellular background in the maintenance of a transformation phenotype was examined in five SV40-transformed teratocarcinoma-derived cell lines. These cell lines show qualitative differences in growth characteristics associated with transformation, and vary in their state of differentiation. Viral T antigen expression was evaluated by two criteria: 1) the amount of immunoprecipitated antigen in growing cells, and 2) the amount and rate of antigen synthesis in density-inhibited cells. There was no direct correlation found between retention, or rate of synthesis, of the viral T antigen and the degree of transformation. These findings imply that the cellular environment has a more important influence on the growth properties of a stably transformed cell than the quantitative levels of viral T antigen expression. PMID- 6251100 TI - Selective high metabolic lability of uridine triphosphate in response to glucosamine feeding of untransformed and polyoma virus-transformed hamster fibroblasts. PMID- 6251102 TI - Nucleic acid bases and derivatives: detection by Dns derivatization thin-layer chromatography. PMID- 6251101 TI - Interactions of insolubilized lectins with membrane glycoproteins in presence of detergents. AB - The effects of several detergents commonly used to solubilize membrane glycoproteins have been investigated on the binding of hepatoma cell surface [3H] galactoglycoproteins to, and their elution from, concanavalin A or Ricinus communis lectins conjugated to Sepharose 4B. The optimum conditions (pH, ionic strength) in the presence of ionic [sodium deoxycholate (DOC) and sodium dodecyl sulphate (SDS)] and non-ionic detergents (Triton X-100) at a constant concentration were determined in order to ascertain which would yield the better efficiency. The effects of different detergent concentrations on binding and elution were then studied. The range of concentrations for each detergent to be used without modifying efficiency was determined. Triton X-100 and DOC (0.1-1%) did not change the efficiency on Ricinus lectin-Sepharose, whereas SDS, at a concentration greater than 0.05%, caused a dramatic decrease in efficiency. On concanavalin A-Sepharose, by contrast, the non-ionic detergent had no effect on the efficiency at all the concentrations tested (0.1-1%), while concentrations of more than 0.5% DOC and 0.1% SDS significantly decreased both binding and elution. PMID- 6251103 TI - Presence and influence of cholinergic nerves in the human thyroid. AB - There is evidence that the sympathetic nervous system exerts a control on human thyroid function via an adrenergic innervation of follicle cells. The present study demonstrates that cholinergic nerve fibers also reach follicle cells in the normal human thyroid. In addition, cholinergic agents were found to enhance cGMP accumulation in human thyroid tissue. This effect was blocked by atropine, a muscarinic receptor antagonist, but not by d-tubocurarine, a nicotinic receptor antagonist. These results provide morphological and biochemical arguments supporting a role of the parasympathetic nervous system in the regulation of thyroid function in man. PMID- 6251104 TI - Parallelism of 11 beta- and 18-hydroxylation demonstrated by urinary free hormones in man. AB - To investigate whether the functions of 11 beta- and 18-hydroxylase are parallel in the human adrenal cortex, we measured urinary free deoxycorticosterone (DOC), free 18-hydroxy-DOC (18-OH-DOC), and free corticosterone (B) in 22 subjects (aged 3 6/12 to 19 yr) before and after metyrapone administration and ACTH infusion. The substrate to product ratio was used as an index of enzyme activity. There were parallel changes in the ratios of DOC to B (11 beta-hydroxylase) and DOC to 18-OH-DOC (18-hydroxylase) in all conditions, while the B to 18-OH-DOC ratio (product ratio) was relatively constant. The correlations between the ratios of DOC to B and DOC to 18-OH-DOC as well as between B and 18-OH-DOC were highly significant under all conditions (r = 0.89; P = 0.00001). These findings are consistent with previous in vitro studies and studies in patients with congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency, suggesting that a single enzyme system is responsible for both 11 beta- and 18-hydroxylation of DOC in the adrenal zona fasciculata. As part of the metyrapone study, 18-OH-B was measured: 18-OH-B values decreased significantly, and the B to 18-OH-B ratio increased during metyrapone administration (from 0.38 +/- 0.09 to 1.79 +/- 0.04; P < 0.005), showing inhibition of 18-hydroxylation of B as well. Since 18-OH-B was suppressed without a decrease in PRA, we concluded that this inhibition is a primary metyrapone effect and not the result of increased DOC and suppressed PRA. PMID- 6251105 TI - Adrenocorticotropin and lipotropin secretion by dispersed cell cultures of a human corticotropic adenoma: effect of hypothalamic extract, arginine vasopressin, hydrocortisone, and serotonin. AB - Basal and modulated secretion of ACTH and lipotropin (LPH) by cultures of trypsin dispersed cells of a biopsy of a human corticotropic adenoma have been examined. ACTH secretion was detectable throughout the period of culture (13 days) but declined steadily from an initial production rate of 238 +/- 124 ng/3 X 10(5) cells/12 h. The time course of secretion showed a slower phase over the first 4 h, with increases up to 12 h. An extract of rat stalk median eminence caused a significant (P less than 0.005) dose-dependent increase in both ACTH and LPH secretion during 30 min. The patterns of response for ACTH and LPH were very similar; both exhibited a decline in the basal release of peptide subsequent to the period of stimulation. The addition of hydrocortisone (0.2 micrograms/ml) did not suppress basal ACTH secretion during 30 min but significantly (P less than 0.05) inhibited stimulation produced by rat stalk median eminence extract. Arginine vasopressin (dose range, 1-9 ng/ml) significantly (P less than 0.025) stimulated both ACTH and LPH secretion during 30 min. The patterns of response were again very similar. Serotonin (dose range, 0.01-10 micrograms/ml) did not affect ACTH secretion during incubations of 30 min to 4 h. The results obtained with the cell cultures of a human corticotropic cell adenoma concur with in vivo findings of incomplete autonomy of secretion, parallel secretion of ACTH and LPH in response to provocative stimuli, and suppression by corticosteroids. The technique has potential for exploring the cellular mechanisms controlling secretion by human corticotropic adenomas as well as the nature of the hormones produced. PMID- 6251106 TI - Corticosteroid-induced differential regulation of beta-adrenergic receptors in circulating human polymorphonuclear leukocytes and mononuclear leukocytes. AB - A method of reproducibility measuring human leukocyte beta-adrenergic receptor density and affinity has been developed and applied to the study of receptor regulation in man. The method has the advantages of using a membrane preparation which binds highly specifically and employing techniques such as using low concentrations of [3H]dihydroalprenol, analyzing the data by computer modelling techniques, and providing data from both granulocytes and lymphocytes in the same individual to minimize measurement errors. Using this methodology, human beta adrenergic receptor regulation is examined. Cortisone acetate was found to induce an acute rise in granulocyte beta-adrenergic receptor density and adenylate cyclase activity and an acute fall in lymphocyte beta-adrenergic receptor density. This potentially differential regulation of a single receptor subtype in two lines of leukocytes has important implications for the study of receptor regulation in man using leukocyte models. PMID- 6251107 TI - Biological effects of various doses of conjugated equine estrogens in postmenopausal women. AB - To determine which dosage of estrogen might provide physiological replacement and also avoid possible harmful side effects, 21 postmenopausal women were studied before and after the oral administration of conjugated equine estrogens. The dosages studied were 0.15, 0.30, 0.625, and 1.25 mg/day, with each being given for 6 weeks. Fifteen premenopausal women were also studied, and their values were presumed to reflect normal physiological function. Variable responses of the different biochemical and biological markers of the action of estrogen were observed. Both LH and FSH levels showed stepwise decreases with increasing amounts of estrogen, but even 1.25 mg/day did not suppress these hormones to the range found in premenopausal women, suggesting a subphysiological response. The lower dosages of conjugated estrogen had minimal effects on vaginal cytology, with only the 1.25-mg dose changing the maturation index to values similar to those found in premenopausal subjects. The 0.3-mg dose of conjugated estrogen was the lowest amount that resulted in a significant reduction (P < 0.05) of the urinary calcium to creatinine ratio (an index of bone resorption). Liver protein synthesis was the most sensitive parameter to the action of estrogen. Hepatic resoponses were variable depending on which protein was assessed. These data indicate that the oral administration of conjugated equine estrogens results in inconsistent effects. All doses exerted subphysiological, physiological, and pharmacological responses at the different sites of action. PMID- 6251108 TI - The attenuated form of congenital adrenal hyperplasia as an allelic form of 21 hydroxylase deficiency. AB - A 17-yr-old female presented with marked menstrual irregularities since menarche at age 13 yr and severe hirsutism, particularly facial, since puberty. Her disorder was shown to be related to a mild 21-hydroxylase deficiency and she was diagnosed to have an attenuated (so-called acquired) form of congenital virilizing adrenal hyperplasia. HLA typing and ACTH testing of her parents and siblings provided evidence of a linkage between HLA and 21-hydroxylase deficiency loci. Similar observations have been made previously for the salt-losing and simple virilizing forms of congenital virilizing adrenal hyperplasia, suggesting that these two as well as the attenuated forms are allelic in regard to the 21 hydroxylase deficiency gene. PMID- 6251109 TI - Thyrotropin-releasing hormone stimulation of adrenocorticotropin production by mouse pituitary tumor cells in culture: possible model for anomalous release of adrenocorticotropin by thyrotropin-releasing hormone in some patients with Cushing's disease and Nelson's syndrome. AB - ACTH-producing mouse pituitary tumor cells in culture (AtT-20/NYU-1 cells) were found to have binding sites for thyrotropin-releasing hormone (TRH). These putative receptors bound TRH with high affinity; the apparent equilibrium dissociation constant was 3.7 nM. The affinity of the receptors for a series of TRH analogues was similar to those previously reported for TRH-receptor interactions on thyrotropic and mammotropic cells in culture. Like some human pituitary tumors in situ, AtT-20/NYU-1 cells were found to produce the alpha subunit of the glycoprotein hormones (alpha). Alpha accumulation in the medium was constant (3.1 ng/mg cell protein per h) and was not affected by TRH. In contrast, TRH increased the amount of ACTH accumulated in the medium from AtT 20/NYU-1 cells to 190 and 420% of control at 1 and 24 h, respectively. TRH induced a dose-dependent increase in ACTH release during a 30-min incubation; half-maximal stimulation occurred at approximately 0.1 nM. TRH had no effect on ACTH release in vitro from anterior pituitary cells derived from normal rats. Because TRH stimulates release of ACTH in some untreated patients with Cushing's disease and Nelson's syndrome as well as pathological states associated with pituitary tumors (but not in normal subjects), AtT-20/NYU-1 cells may serve as an important in vitro model for human pituitary ACTH-secreting adenomas. Moreover, these findings suggest that the primary abnormality in Cushing's disease and Nelson's syndrome, allowing TRH stimulation of ACTH release, may be intrinsic to neoplastic adrenocorticotrophs rather than in neuroregulation of ACTH release. PMID- 6251110 TI - Calcium and inorganic phosphate transport in rat colon: dissociated response to 1,25-dihydroxyvitamin D3. AB - In the small intestine, 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] stimulates both calcium (Ca) and inorganic phosphate (Pi) absorption. This is mediated through an increase in mucosal-to-serosal flux (Jms) whereas the serosal-to mucosal flux (Jsm) remains unchanged. We now report that in rat proximal colon, 1,25(OH)(2)D(3) produces active Ca absorption without affecting Pi transport, and that this induced active Ca absorption is associated with alterations in kinetics of both Jms and Jsm so that both processes demonstrate saturable components. Vitamin D-deficient rats were given daily injections of solvent (-D) or 270 ng 1,25(OH)(2)D(3) (+D) for 3 d. (45)Ca and [(32)P]phosphate fluxes were measured employing the Ussing technique using a modified Krebs-Ringer-HCO(3) buffer ([Ca] 1.25, [Pi] 1.18, [glucose] 11 mM). In -D rats there was no net flux (Jnet) of either Ca or Pi. In +D rats net active Ca absorption was observed (-D = 3.3 nmol/cm(2) per h +/-3.4 (SEM); +D = 27.3 +/-3.8, n = 11, P < 0.001) whereas Pi transport was unchanged, i.e., still no Jnet. Pi Jms was not different from Pi Jsm measured at the following buffer [Pi]: 0.0118, 0.118, 1.18, and 2.36 mM. Ca saturation kinetics were estimated using buffer [Ca] from 0.0125 to 5.0 mM. Saturable processes were demonstrated for both Jms and Jsm. Jnet for Ca across colon from +D rats exhibited saturation at [Ca] > 3 mM, with an estimated V(max) of 44.0 nmol/cm(2) per h and a K(m) of 0.9 mM. This colonic model may provide a useful system for studying 1,25(OH)(2)D(3)-induced molecular events related to Ca but not Pi transport. The apparent action of 1,25(OH)(2)D(3) on Ca secretory process may furnish new insights into the mechanism of action of vitamin D. PMID- 6251111 TI - Constituents of human neutrophils that mediate enhanced adherence to surfaces: purification and identification as acidic proteins of the specific granules. AB - The endogenous constituents of human neutrophils that enhance the adherence of the neutrophils to surfaces have been isolated from sonicates of purified neutrophils. The predominant adherence-enhancing activity in the neutrophil sonicates cofiltered on Sephadex G-75 with a major peak of chemotactic inhibitory activity and exhibited approximately 30,000 mol wt. Sequential isoelectric focusing and electrophoresis in glycerol gradients of the 30,000-mol wt activities resolved two distinct acidic protein with isoelectric points of 3.6 3.8 and 3.3-3.4 that were designated the neutrophil adherence factor (NAF) I and II, respectively. Glutamic acid and aspartic acid together accounted for a total of 18 and 19% of the amino acids in purified preparations of NAF I and NAF II, respectively, whereas the basic amino acids lysine, arginine, and histidine represented <2 and 3% of the total residues. The preincubation of portions of 2 x 10(6) neutrophils with as little as 6 pmol of NAF I or 9 pmol of NAF II enhanced adherence to plastic petri dishes and inhibited chemotactic migration to a maximal extent, with comparable dose-response relationships for the two effects. Neither of the NAF was cytotoxic, exhibited substantial neutrophil chemotactic or chemokinetic activity, or influenced the phagocytosis of sheep erythrocytes sensitized with immunoglobulin (Ig)G. Analyses of subcellular fractions of neutrophils indicated that the NAF are contained predominantly in the specific granules. These distinctive acidic proteins of the specific granules of human neutrophils represent a new class of endogenous constituents that may regulate the involvement of neutrophils in inflammation. PMID- 6251112 TI - Effect of portal venous blood flow diversion on portal pressure. AB - To anticipate the hepatic vascular response to portacaval anastomosis, we studied portal pressure during diversion of portal blood through a temporary extracorporeal umbilical vein to saphenous vein shunt. The relationship of portal pressure to shunted flow was approximately linear. In five schistosomiasis patients (controls) portal diversion to 1,250 ml/min gave portal pressure-shunted flow curve slopes ranging from 0.13 to 0.57 cm water/100 ml per min (0.31+/-0.18, mean+/-SD). In 17 cirrhotic patients with portal hypertension a continuum of slopes was observed from within mean+/-2 SD of control (type A) to larger slopes (type B) indicating failure of portal pressure regulation. When portal flow was augmented by shunting from saphenous vein to portal vein, cirrhotic patients who had slopes less than mean+/-2 SD of controls during diversion (type A) exhibited a compliant system with small increases in portal pressure, whereas type B patients had significantly greater pressure increases. Selective investigations suggested that changes in portal pressure provoked compensatory changes in hepatic arterial blood flow that tended to maintain portal pressure at a set point. Type B patients demonstrated failure of this mechanism to varying degrees.After end-to-side portacaval shunt, seven type A cirrhotic patients maintained residual intrahepatic venous pressure unchanged from prior portal pressure, whereas six type B patients had a significant decrease. Residual intrahepatic venous pressure was measured after portacaval shunt in 40 cirrhotic patients who were followed for as long as 9 yr (median survival 4.0 yr). The 13 patients who developed chronic encephalopathy had significantly lower pressure (21.1+/-4.4 cm, mean+/-SD) and shorter survival (median 0.6 yr) than the other 27 patients (32.6+/-5.3 cm, 5.0 yr). The preoperative estimation of portal pressure diverted portal flow curve slope anticipates the hepatic vascular response to portacaval anastomosis and identifies a group of patients in whom loss of portal blood flow results in a low residual intrahepatic venous pressure that is associated with early death and chronic encephalopathy. PMID- 6251113 TI - Parathyroid hormone acutely increases polyphosphoinositides of the rabbit kidney cortex by a cycloheximide-sensitive process. AB - Parathyroid hormone(PTH) rapidly increases the concentrations of diphosphoinositide and triphosphoinositide in rabbit kidney cortex. Cycloheximide pretreatment abolishes these effects of PTH. These findings are similar to those reported for adrenocorticotropin and cyclic AMP action in the adrenal cortex, and suggest a common mechanism. Cycloheximide-sensitive effects of PTH, e.g., phosphaturia, may require polyphosphoinositides and/or other phospholipids. PMID- 6251114 TI - Inhibitory action of a met-enkephalin on ACTH release in man. AB - In order to study the mechanism of action of a Met-enkephalin (FK 33824) on the pituitary-adrenal axis eight normal male volunteers were subjected to an ACTH stimulation test. Lysine-vasopressing (LVP), 5 IU, was injected intramuscularly after pretreatment with 0.5 mg FK 33824 i.m. or a placebo. In six of the subjects the opiate was again administered preceding a single injection of 0.25 mg ACTH beta 1-24 i.m. Blood was collected at regular intervals and ACTH and cortisol concentrations analyzed in all samples. LVP induced significant plasma ACTH (P < 0.05) and cortisol (P < 0.001) increases. Pretreatment with FK 33824 completely antagonized the effect of LVP. Furthermore, the cortisol elevation after exogenous ACTH was not modified by previous administration of FK 33824. It is concluded that the Met-enkephalin derivative FK 33824 directly suppresses ACTH release from the pituitary without influencing adrenal synthesis of cortisol. PMID- 6251115 TI - Echocardiographic detection of metastatic cardiac mural tumor. PMID- 6251116 TI - Glucocorticoids, the hippocampus, and behavior: interactive relation between task activation and steroid hormone binding specificity. AB - A previous investigation established a modulatory effect of adrenal glucocorticoids on a behavior generally believed to require participation of the hippocampus for normal expression. For further delineation of whether the observed effects on appetitive extinction are consistent with a glucocorticoid action on hippocampus, adrenalectomized rats were administered either corticosterone or dexamethasone, a synthetic glucocorticoid that is accumulated much less intensively by the hippocampus than is corticosterone. While corticosterone normalized extinction, dexamethasone did not. In two other hippocampal-dependent behaviors, alternation and exploration, there was no glucocorticoid modulation of behavior, which may indicate that factors such as the level of activation of the type of learning determine whether a glucocorticoid effect will occur. These findings of a glucocorticoid action on one of three tasks that involve hippocampal function reinforce the notion that in addition to their well-studied actions in protein and carbohydrate metabolism, the adrenal glucocorticoids may also be subtle modulators of behavior. PMID- 6251117 TI - Opiates and homing. AB - Beginning at 15 days of age. Long-Evans rat pups were trained to run toward their home cage in a T-maze task. Morphine (.5-1.0 mg/kg sc) slowed initial acquisition running times but did not change the number of trials required to learn the position habit. Morphine markedly impeded extinction of the homing behavior. Opiate-treated animals ran as accurately and as quickly toward home on the 12th day of extinction as on the first (10 trials given per day). Conversely, naloxone (1 mg/kg sc) reduced resistance to extinction. The morphine effect was not state dependent since the drug also impeded extinction in animals that had acquired the task under saline. The morphine effect was blocked by naloxane, which indicates that the increased resistance to extinction was due to an opiate receptor effect. These results indicate that morphine has a strong capacity to sustain a social habit in the absence of reinforcement. PMID- 6251118 TI - CT demonstration of portal and superior mesenteric vein thrombosis in hepatocellular carcinoma. AB - Three cases of hepatocellular carcinoma in which computed tomography (CT) demonstrated thrombosis of the portal vein are reported. In one patient, extension of the thrombus into the superior mesenteric vein was identified as well. The outstanding CT features of portal vein thrombosis were: (a) enlargement of the vein, (b) intraluminal low density area, and (c) hyperdense peripheral ring due to the enhancement of the venous wall. These findings may be useful in differentiating hepatocellular carcinoma from hepatic metastases. PMID- 6251119 TI - Early two-dimensional reconstruction (CT scanning) and recent topics stemming from it. Nobel lecture, December 8, 1979. PMID- 6251121 TI - Effects of acetylcholine and nitroprusside on cGMP-dependent protein kinase in the perfused rat heart. AB - The effects of acetylcholine and sodium nitroprusside on the activity of cGMP dependent protein kinase were studied in the perfused rat heart. Acetylcholine produced a dose-dependent increase in cGMP levels and cGMP-dependent protein kinase activity, and reduced the force of contraction. Both acetylcholine and sodium nitroprusside produced rapid increases in cardiac cGMP, with nitroprusside being the more potent agent. Only acetylcholine, however, raised the activity ratio of the cGMP-dependent protein kinase and decreased the force of contraction. Whereas acetylcholine and nitroprusside were slightly additive in their effects on total cGMP levels, the increase in the activity ratio of the cGMP-dependent protein kinase and the decrease in the force of contraction produced by acetylcholine were unchanged by nitroprusside. The results suggest that the cGMP produced by acetylcholine, but not nitroprusside, was coupled to protein kinase activation in this tissue. PMID- 6251120 TI - Interaction between alpha and beta adrenergic receptors and cholinergic receptors in isolated perfused rat heart: effects on cAMP-protein kinase and phosphorylase. AB - The ability of acetylcholine to antagonize catecholamine-induced activation of myocardial cyclic AMP dependent protein kinase and glycogen phosphorylase activity was assessed using isolated perfused rat hearts. Perfused hearts were treated with either saline, epinephrine, epinephrine plus phentolamine or isoproterenol. After 1 minute of infusion of the indicated drug a second infusion containing acetylcholine was started. After an additional minute hearts were frozen and analyzed for cyclic nucleotide content and enzyme activity. In the presence of the alpha receptor blocking agent, phentolamine, epinephrine is a more effective activator of protein kinase than in its absence. Under these conditions the antagonistic action of acetylcholine on protein kinase activation is more pronounced. In the presence of epinephrine plus phentolamine or in the presence of isoproterenol the antagonistic action of acetylcholine on phosphorylase activity can be accounted for by a reduction in cyclic AMP-protein kinase. This same action of acetylcholine on epinephrine-stimulated phosphorylase in the aabsence of phentolamine, however, cannot be totally accounted for by a reduction in cyclic AMP content or in protein kinase activity. PMID- 6251122 TI - Residual cyclic nucleotide associated with tissues after exposure to aqueous buffer analogous to that used in immunocytochemistry. AB - A question concerning cyclic nucleotide immunocytochemical localization has been how much nucleotide remains associated with the tissue section. To answer that question cryostat sections of goldfish eye and mouse spleen, liver and lung were mounted on microscope slides and air dried. Following fixation by a variety of procedures employing heat, paraformaldehyde, glutaraldehyde, acetone, or ethanol, the sections were exposed to buffer (20 microM NaHPO4, 154 microM NaCl, pH 6.1) for 4 hours. The tissues were then scraped from the slides into 0.4N Perchloric Acid and cAMP and cGMP extracted and measured. The results show that fractions of both nucleotides are retained during buffer exposure. However, the amount retained varied with the: i) neucleotide, ii) fixation procedure, and iii) tissue type. Cyclic GMP retention was consistently higher (20-70%) than cAMP (6-30%). Glutaraldehyde was consistently more efficient in fixing cAMP, while cGMP retention was more variable with different fixation procedures. Tissue variability is seen in the example that spleen and liver retained more cGmp (71.4 and 70.6% respectively) than lung and eye (22.8 and 37.7% respectively). Maximum nucleotide loss occured during the first 5-30 minutes of buffer exposure with no additional loss accuring after another 20 hours. Collectively, these results demonstrate that cyclic nucleotides are retained during immunocytochemical staining procedures but that the degree of retention is dependent on several variables. PMID- 6251123 TI - [Formation of a complex of spin label 9-aminoacridine with DNA and polynucleotides]. PMID- 6251124 TI - Development of a mental health programme in the Central Coast of New South Wales, Australia. AB - The Central Coast Programme is considered to have begun in December 1969 with the arrival and commitment of Dr Donald Scott-Orr (specialist psychiatrist) in the Central Coast, and with the parallel commitment of the then Medical Superintendent of Morisset Hospital, Dr Howard Gorton to support the development of a regional programme for the Central Coast. It was decided not to re-establish any clinics and so avoid waiting lists. There was an emphasis on groups as a means of interaction and a family orientation in the work. In the early years the role of the nurse was changing. Initially, the extramural role was expected by the hospital to be 'following-up' patients. However, the service was based on commitment to a community rather than hospital. Increasingly the nurses' work was directly referred to them independently of hospital admissions. Staff visited general practitioners (GPs) on the Central Coast in their surgeries and regular letters were sent keeping the GPs informed of changes in the service. Consultations and transactions were recorded on referral forms and files were opened on all persons concerning whom the service was consulted. A client's name was always linked with the name of their general practitioner who was encouraged to make telephone contact freely to seek consultative support in connection with problems in their practice. Priority for crisis intervention and orientation towards family and group was backed up by domiciliary visits and widespread communication and consultation. The attempt was made to use therapeutic community principles for the in-patient programme. The processes of care were seen as being as important as the content of care in assuring an optimum quality care. There is a continuing need to focus on the flexible interchange between intra- and extra mural staff in providing continuity for clients in care and integration with primary care services and agencies. In January 1978 Dr Max Chapman was appointed director of the psychiatric and mental health services on the Central Coast and he is currently in that position. PMID- 6251125 TI - Occupational asthma: review of present clinical and immunologic status. PMID- 6251126 TI - Radioallergosorbent testing of toluene diisocyanate-reactive individuals using p tolyl isocyanate antigen. AB - Serum from 26 persons shown to react to provocative inhalation challenge with low concentration of toluene diisocyanate (TDI) was tested by radioallergosorbent test (RAST) using a p-tolyl isocyanate-human serum albumin (TMI-HSA) conjugate. Results were evaluated by the RAST ratio and by the mean +3 standard deviation methods. Positive results were obtained in 15% to 19% of TDI reactors, depending on the method of evaluation. These findings suggest that TDI asthma may be a complex syndrome with several types of reaction possible, including an IgE mechanism in some individuals, but they do not support the theory that TDI asthma is based solely on an immune mechanism. However, they do not disagree with the hypothesis that TDI reactivity may be mediated by a pharmacologic mechanism. PMID- 6251127 TI - In vitro effects of radiographic contrast media on the complement system. AB - The effect of several radiographic contrast media on the complement system in vitro was examined using quantitative crossed immunoelectrophoresis. Diatrizoate, iothalamate, metrizoate, and methiodal did not cause electrophoretic conversion of C3 or properdin factor B. In fact, the small degree of spontaneous conversion occurring when serum is incubated in polypropylene tubes was inhibited by these contrast media or by hypertonic sodium chloride. Metrizamide caused enhanced conversion of C3 and factor B that was only partially inhibited by ethylene glycol tetracetic acid (EGTA) but completely inhibited by ethylenediaminetetraacetic acid (EDTA). Iodipamide caused a unique electrophoretic alteration of C3 that was not affected by EDTA or several other inhibitors and that was not identical with the usual products of C3 activation. Iodipamide in very low concentrations inhibited complement activation through the classical pathway. PMID- 6251128 TI - Alleviation of constipation in the elderly by dietary fiber supplementation. AB - To alleviate the constipation problem among the elderly residents of Essex County Geriatric Center, New Jersey, a fiber-supplemented dietary regimen was started. Under this regimen, bran was added to the hot breakfast cereal, thus increasing the crude fiber content of the diet to 6-8 gm compared with the former 4-6 gm. As estimated from recent analysis data, the total dietary fiber was increased from 25 to 40 percent by the addition of bran. This amount of fiber proved effective in preventing constipation in 60 percent of the residents even though many of them had previously required laxatives. Additional programs of dietary fiber supplementation were devised for residents who did not respond to the cereal supplementation or who required nasogastric feedings. In the year following initiation of the program at this Center, the use of laxatives was virtually eliminated, and the institution's pharmacy reported a saving of $44,000 in expenditures for laxative drugs. Recipes are included for the bran-supplemented hot cereal, a special fiber-prune juice supplement, and a fiber-rich liquid for tube-feedings. PMID- 6251129 TI - Evaluation of a dietary regimen for chronic constipation. Report of a pilot study. PMID- 6251130 TI - Varicella morbidity in Czechoslovakia. AB - Data are presented on varicella and herpes zoster morbidity notified in Czechoslovakia in the years 1970 to 1978. The notified varicella incidence is compared with serologically confirmed varicella incidence among the selected groups of children up to the age of 12 from the North-Moravia region. Comparative analysis revealed a considerable difference between the notified and serologically detected cases of varicella. The highest rate of notified varicella was recorded in children of 3 and 4 years of age, while the highest incidence of seropositive cases was detected among the 2-year-old children. The cumulative notified morbidity involved about 35% of 6-year-old and 45% of 12-year-old children, whereas specific antibodies against the varicella-zoster virus were found in about 60% of 6-year-old and 90% of 12-year-old children. The titres of virus-specific antibodies were determined by the method of indirect hemagglutination reaction. No serological methods are applicable for herpes zoster morbidity studies in the population. PMID- 6251131 TI - Appendicectomy and dietary fibre. AB - The hypothesis that dietary fibre protects against appendicitis was tested. One thousand seven hundred subjects, involved in another enquiry, were sent a questionnaire asking about their intake of cereal fibre and other foodstuffs, and whether or not they had had an appendectomy. The respondents, who represented 92 per cent of the sample, were divided into those who ate wholemeal bread daily and those who ate wholemeal bread rarely or never. These groups appeared to be very similar with respect to age, sex, smoking habit, alcohol intake and various other factors. Comparison of appendicectomy rates between those who ate wholemeal bread and those who did not showed a deficit among the former, which is consistent with a protective effect of cereal fibre, but the difference was not statistically significant. PMID- 6251132 TI - The cellular basis for viral-induced immunodeficiency: analysis by monoclonal antibodies. AB - Viral infections are often associated with immunodeficiency states. Although T lymphocytes have been thought to suppress the host's response, the precise etiology remains unclear. Therefore, we characterized T lymphocytes from six patients during both acute and convalescent phases of infectious mononucleosis (IM) with monoclonal antibodies (titer, 10(-5) to 10(-7) to antigens restricted to the TH2- helper (T4) and TH2 suppressor (T5) T cell subsets as well as to a common T cell antigen (T3) and HLA-D related Ia antigens. It was found that during acute infectious mononucleosis, there is both activation and increase of suppressor T cells (T5+, Ia+ phenotype). Fuctionally, the acute IM lymphocytes suppress autologous T cell proliferation to antigens as well as pokeweed mitogen driven B cell immunoglobulin production. In contrast, convalescence is associated with a return to normal of T cell subsets and immune function. These results demonstrate that viral infections can preferentially activate a specific T cell subset and suppress the overall human immune response. PMID- 6251133 TI - Changes in macrophage ectoenzymes associated with anti-tumor activity. AB - The phenotype of three ectoenzymes was determined for murine resident peritoneal macrophages, macrophages elicited in vivo by treatment of mice with thioglycollate, Corynebacterium parvum or pyran, and for resident macrophages activated in vitro by treatment with lymphokine. The relationship of these biochemical markers to macrophage antiviral and anti-tumor activity was established. Thioglycollate-elicited macrophages showed a unique ectoenzyme phenotype, with increased leucine aminopeptidase and alkaline phosphodiesterase I activity and markedly reduced 5'-nucleotidase activity as compared with resident macrophages. Thioglycollate-elicited macrophages exhibited extrinsic antiviral activity against herpes simplex virus but did not show anti-tumor activity. Another ectoenzyme phenotype was shared by macrophages elicited in vivo by treatment of mice with the immunomodulators or in vitro by treatment with antigen specific lymphokine. These macrophage populations showed increased levels of leucine aminopeptidase but reduced levels of both 5'-nucleotidase and alkaline phosphodiesterase. This ectoenzyme phenotype was associated with the acquisition by the macrophages of selective anti-tumor activity. There appear to be clear distinctions in biochemical markers and functional properties among macrophages activated by different mechanisms. PMID- 6251134 TI - Effects of prostaglandin D2 on rat serosal mast cells: discordance between immunologic mediator release and cyclic AMP levels. PMID- 6251135 TI - Minimal molecular and cellular requirements for elicitation of secondary anti vesicular stomatitis virus cytotoxic T lymphocytes. PMID- 6251136 TI - Antigenic modulation as a mechanism for tumor escape from immune destruction: identification of modulation-positive and modulation-negative mouse lymphomas with xenoantisera to murine leukemia virus gp70. PMID- 6251138 TI - Activation of lymphocytes from Epstein-Barr virus-seronegative donors by autologous Epstein-Barr virus-transformed cells. AB - The activation of peripheral lymphocytes by Epstein-Barr virus (EBV)-transformed cells was tested in the autologous system. EBV-transformed cells activated autologous lymphocytes from all 10 healthy subjects regardless of their status of antibody to EBV. Lymphocytes from three neonates were also activated by autologous EBV-transformed cells. It was concluded that activation of lymphocytes by autologous EBV-transformed cells is a nonspecific phenomenon in the sense that prior infection by EBV is not a prerequisite for responsiveness of lymphocytes to autologous EBV-transformed cells. The responding cells were found predominantly in the T cell-enriched fraction. This finding is of no interest because the pathogenesis of, and recovery from, infectious mononucleosis may depend in part on this nonspecific phenomenon. PMID- 6251137 TI - Use of benzoyl-L-phenylalanyl-L-valyl-L-arginine (3H) methyl ester as a sensitive and selective substrate for the human lymphokine, leukocyte migration inhibitory factor (LIF). AB - Human leukocyte migration inhibitory factor (LIF) appears to be a serine esterase and protease exhibiting specific affinity towards arginine esters and amides. On the basis of indirect evidence that an amide of the oligopeptide benzoyl phenylalanyl-valyl-arginine might have high and selective affinity for LIF, we prepared an ester of this oligopeptide, benzoyl-phenylalanyl-valyl-arginine (3H) methyl ester (3H-BPVAME) for the direct measurement of LIF activity in a double phase radio-enzyme assay. The hydrolysis of 3H-BPVAME followed enzyme-substrate kinetics in that the reaction was time-, temperature-, pH-, and concentration dependent. 3H-BPVAME rpoved to be more selective and approximately 20 times more sensitive as a substrate for LIF than previously used radiolabeled substrates such as 3H-BAEE and 3H-TAME. Moreover, hydrolysis of 3H-BPVAME by partially purified LIF preparations was significantly inhibited by 10(-8) to 10 (-5) M of guanosine 3',5'-cyclic monophosphate (cGMP), further supporting the hypothesis that cGMP acts as a regulator of LIF activity. Inhibition of LIF-induced esterolysis was also provided by dibutyryl cGMP, but only at concentrations 10( 7) to 10(-5) M; 8-bromo cGMP and adenosine 3',5'-cyclic monophosphate were both ineffective. These results provide support for the use of 3H-BPVAME as a more selective substrate to detect esterase activity in LIF preparations than heretofore described and the possible development of a biochemical assay for the measurement of this lymphokine. PMID- 6251139 TI - Experimental endotoxin shock: the pathophysiologic function of endorphins and treatment with opiate antagonists. AB - The specific opiate-antagonist naloxone rapidly reverses hypotension caused by endotoxin, hypovolemia, and spinal transection. In endotoxin shock in rats, naloxone's effects were stereospecific and were observed with intravenous (iv) doses as low as 0.1 mg/kg. In endotoxin shock in dogs, naloxone treatment significantly improved both cardiovascular parameters and survival. Naloxone, given iv, similarly improved blood pressure and survival in rat and canine models of hypovolemic shock. Moreover, intracerebroventricular (ivt) naloxone at a dose of 10 micrograms restored blood pressure after hypovolemia; this effect was blocked by hypophysectomy. In addition naloxone, given ivt, stereospecifically restored blood prssure after spinal shock. From these findings it is suggested that (1) pituitary endorphins are pathophysiologic factors in shock; (2) endorphins' cardiodepressant effects are mediated by opiate receptors within the central nervous system; and (3) use of opiate antagonists may be of therapeutic benefit in the treatment of shock in humans. PMID- 6251140 TI - Rheumatoid factor in acute viral infections: interference with determination of IgM, IgG, and IgA antibodies in an enzyme immunoassay. AB - IgM rheumatoid factor (RF), an autoantibody to the Fc fragment of IgG, was determined by solid-phase enzyme immunoassay (EIA). RF levels were significantly higher in patients with rubella virus infection than in patients with infections due to influenza virus, cytomegalovirus, respiratory syncytial virus, parainfluenza virus, adenovirus, mumps virus, or herpes simplex virus. To evaluate the role of RF in EIA determinations of viral antibodies, IgM RF from IgM-IgG cryoglobulin or control IgM was added to patient sera before assay for viral antibodies. IgM RF inhibited virus-specific IgG and IgA reactions and gave nonspecific IgM reactions in EIA for antibodies to rubella and influenza viruses, but had little or no effect on antibodies to cytomegalovirus. The minimal effective amounts of RF were 100-500 ng/ml for inhibition of IgG, 300-1,000 ng/ml for IgA, and 25-500 ng/ml for IgM. The control IgM preparation gave no such effects. These studies reinforce the need to eliminate RF interference in solid phase EIA. PMID- 6251141 TI - Poliovirus type 3 keratoconjunctivitis. PMID- 6251142 TI - [A case of cervical pheochromocytoma (author's transl)]. PMID- 6251143 TI - [A case of antidiuretic hormone, oxytocin and clacitonin producing oat cell carcinoma of the lung with prominent peritoneal carcinomatosis (author's transl)]. PMID- 6251144 TI - Dead wrong--estrogens, osteoporosis cancer and public policy. AB - Practicing physicians must constantly decide what is the best treatment for each patient. Their decisions are often influenced by prominent professors and by a climate of opinion created by the press and regulatory agencies. If these are wrong, because of pressure from 'consumer advocates', wrong interpretations, or the risks of litigation, physicians may be forced into making inactive decisions which can cause more harm than the treatment under attack. My attention was drawn to this problem by recent actions of the press and the FDA discouraging the use of estrogens because of a putative risk of endometrial cancer. Even if the danger were real, and I consider the evidence faulty, doctors would have to balance risks against benefits. We have 2,718 deaths each year, constant for ten years, from endometrial cancer and at least 50,000 female deaths because of preventable osteoporotic hip fractures. Recent data establish that the doses of estrogen needed to prevent postmenopausal bone loss are lower than those associated with any cancer. History abounds with similar examples. Semmelweis showed that handwashing prevented deaths from puerperal sepsis but was laughed into a madhouse. More recent examples are the long delays in the use of propranolol, cimetidine, bromcryptine, pulmonary surgery, antihypertensive therapy, poliomyelitis vaccination, penicillin and cardiac surgery. An approach to correction of this serious problem will be presented. PMID- 6251145 TI - Sclerosing hemangioma of the lung: report of a case with an ultrastructural study. PMID- 6251146 TI - Liver cell dysplasia in cirrhosis and liver cell carcinoma. PMID- 6251147 TI - atypical fibrous histiocytoma of the lung: a case report. PMID- 6251148 TI - Chromatographic characterization of adsrenocorticotrophin in human plasma. AB - A chromatographic procedure has been developed for the characterization of ACTH- and lipotrophin- (LPH) related peptides in human plasma under acid-dissociating conditions to minimize artifacts of protein binding. The recovery and sensitivity of this method permits identification of ACTH at normal physiological levels in the circulation. Plasma profiles obtained from normal subjects and patients with pituitary dependent Cushing's disease, Addison's disease and Nelson's syndsrome showed only one significant peak of ACTH activity eluting in the position of purified native human 1--39 ACTH. However, the plasma profiles obtained from all the patients with the ectopic ACTH syndrome demonstrated a second peak of immunoreactive larger-molecular-weight ACTH and in some plasma samples this was the only form of ACTH observed. This larger-molecular-weight ACTH eluted midway between the void volume and 1--39 ACTH and co-eluted with a protein marker of molecular weight 22 000. PMID- 6251149 TI - Oestrogen-induced myometrial quiescence in the post-partum rat is not mediated by adrenaline or by alpha- or beta-adrenoceptor activation. AB - Ovariectomized post-partum rats exhibit in vivo continuous stable myometrial activity with a frequency of 45--50 pressure cycles per h, and a mean maximum amplitude of 45--50 mmHg for many days. Oestradiol benzoate (5 micrograms) reduced the frequency of intra-uterine pressure cycles to 5 cycles per h by 20 h after treatment. The decrease in frequency was due to increased periods of uterine quiescence. Pretreatment with reserpine caused significant reductions in the concentration of uterine adrenaline and noradrenaline as measured by a fluorometric assay but had no effect on the extent or time-course of oestrogen induced myometrial quiescence. Neither intravenous infusion of the adrenergic beta-blocker, propranolol, altered the extent or the time-course of the reduction of intra-uterine pressure cycles after oestrogen treatment. These results suggest that the mechanism by which oestrogen induces myometrial quiescence does not involve adrenaline mediation or alpha- or beta-adrenoceptor activation. PMID- 6251151 TI - Hormonal regulations of follicle-stimulating hormone receptors in the tests of Japanese quail. PMID- 6251150 TI - Cyclic AMP levels in purified rat adrenal zonae fasciculata and reticularis cells and the effect of adrenocorticotrophic hormone. AB - Cyclic AMP levels were measured in combined cells and supernatant fraction from incubations of dispersed rat adrenal zona fasciculata and zona reticularis cell preparations purified by unit gravity sedimentation. These measurements were correlated with deoxycorticosterone (DOC) and corticosterone outputs from the cells in the presence or absence of ACTH. Similar measurements of cyclic AMP outputs were made for unpurified dispersed, decapsulated rat adrenal cell preparations and they were found to correspond to previously reported measurements made by other workers on such preparations. The response of the purest zona reticularis cells to ACTH in terms of cyclic AMP output was 28-fold lower than that of the purest zona fasciculata cells (compared with a fivefold lower DOC output and a 20-fold lower corticosterone output) and the response to ACTH of the mixed-cell preparations was related to the number of zona fasciculata cells in the preparation, i.e. the greater the proportion of zona fasciculata cells in the preparation the greater the response in terms of both outputs of cyclic AMP and of either of the two steroids measured. This correlation is in accordance with the theory that cyclic AMP may be the secondary messenger for both zona fasciculata and zona reticularis cells of the rat adrenal cortex in mediating the response to an ACTH stimulus. PMID- 6251152 TI - Stability of the Third International Standard for corticotrophin: accelerated degradation study using different bioassays and isoelectric focusing. PMID- 6251153 TI - Localization of a gene for expression of mouse mammary tumor virus antigens in the GR/Mtv-2- mouse strain. AB - The GR/Mtv-2- mouse strain is congenic to the GR strain but lacks the Mtv-2 gene for high amounts of mouse mammary tumor virus (MMTV) virion particles in the milk and early mammary tumors. With a sensitive competition radioimmunoassay for individual viral proteins of MMTV, substantial amounts of the gag proteins p27 and p10 could still be detected in extracts of the mammary glands of GR/Mtv-2- mice, but essentially no viral envelope antigens. The genetic transmission of the MMTV gag expression in the GR/Mtv-2- strain was investigated. In a cross with the virus-negative BALB/c strain, the MMTV p27 expression behaved as a dominant feature. Double backcross analysis proved that the p27 expression was governed by a single gene located on chromosome 11, cloe to the Es-3 locus. The gene was thereby not allelic to any of the previously described MMTV induction genes, Mtv 1 and Mtv-2, and is therefore called Mtv-3. It is concluded that the total MMTV expression in the GR strain is under control of two separate loci, Mtv-2 on chromosome 18, inducing high levels of complete virus particles and also early mammary tumors; and Mtv-3 on chromosome 11, coding for partial MMTV expression. PMID- 6251154 TI - Effect of cAMP and related compounds on newt epidermal cell migration both in vivo and in vitro. AB - The effect of cyclic AMP and related compounds on both in vivo and in vitro epidermal cell migration during wound closure in the adult newt was examined. Cyclic AMP (cAMP) and N6,O2'-dibutyryl cyclic AMP (db-cAMP) inhibited migration both in vivo and in vitro when used with equimolar concentrations of theophylline, an inhibitor of 3',5'-cyclic nucleotide phosphodiesterase. Neither db-cAMP nor theophylline alone inhibited migration in vivo. Adenosine 5' monophosphate (AMP), cyclic guanosine 3',5' monophosphate (cGMP) and imidazole, a potentiator of phosphodiesterase were tested in vivo and had no effect on migration. Isoproterenol and epinephrine, which are known to stimulate adenylate cyclase, inhibited migration in vitro. Experiments using the protein synthesis inhibitor, cycloheximide, suggest that cAMP could be acting partially through regulation of protein synthesis but that other factors are involved. Dibutyryl cyclic AMP and theophylline had no effect on the incorporation of 3H-leucine into protein. The inhibition of migration both in vivo and in vitro provides further evidence for a role of cAMP in the regulation of cell motility. PMID- 6251155 TI - Receptive fields of second-order neurons in the olfactory bulb of the hamster. AB - Electrical stimulation of nerve fibers emerging from different positions of the olfactory epithelium was used to determine the receptive fields for 52 olfactory bulb neurons in the hamster. The responses of olfactory bulb neurons were recorded extracellularly with metal-filled micropipettes. Suprathreshold stimuli (500 microA) were applied to each of eight standard epithelial positions spaced approximately 250 microns apart, and the position, or positions, which, when stimulated, produced a response in the bulb were taken as an index of the neuron's receptive field. The results indicate that most bulb neurons have very localized receptive fields limited to only one or two stimulating positions. Furthermore, there was a statistically significant correlation between the location of a neuron's receptive field in the olfactory epithelium and the recording depth of the neuron in the olfactory bulb (Spearman rank correlation coefficient, rs, 0.67, P < 0.001). These findings demonstrate that in the mammalian olfactory system there exists a topographical projection of input from localized regions in the epithelium onto the second-order neurons in the olfactory bulb. PMID- 6251156 TI - Facilitation, augmentation, and potentiation of synaptic transmission at the superior cervical ganglion of the rabbit. AB - The effect of repetitive stimulation on synaptic transmission was studied in the isolated superior cervical ganglion of the rabbit under conditions of reduced quantal content. Excitatory postsynaptic potentials (EPSP) were recorded with the sucrose gap technique to obtain estimates of transmitter release. Four components of increased transmitter release, with time constants of decay similar to those observed at the frog neuromuscular junction at 20 degrees C, were found in the ganglion at 34 degrees C: a first component of facilitation, which decayed with a time constant of 59 +/- 14 ms (mean +/- SD); a second component of facilitation, which decayed with a time constant of 388 +/- 97 ms; augmentation, which decayed with a time constant of 7.2 +/- 1 s; and potentiation, which decayed with a time constant of 88 +/- 25 s. The addition of 0.1-0.2 mM Ba2+ to the Locke solution increased the magnitude but not the time constant of decay of augmentation. Ba2+ had little effect on potentiation. The addition of 0.2-0.8 mM Sr2+ to the Locke solution appeared to increase the magnitude of the second component of facilitation. Sr2+ had little effect on augmentation or potentiation. These selective effects of Ba2+ and Sr2+ on the components of increased transmitter release in the rabbit ganglion are similar to the effects of these ions at the frog neuromuscular junction. Although the effects of Ba2+ and Sr2+ are similar in the two preparations, the magnitudes of augmentation and the second component of facilitation after a single impulse were about 6-10 times greater in the rabbit ganglion than at the frog neuromuscular junction. These results suggest that the underlying mechanisms in the nerve terminal that give rise to the components of increased transmitter release in the rabbit ganglion and frog neuromuscular junction are similar but not identical. PMID- 6251157 TI - Cationic selectivity and competition at the sodium entry site in frog skin. AB - The cation selectivity of the Na entry mechanism located in the outer membrane of the bullfrog (Rana catesbeiana) skin epithelium was studied. This selectivity was determined by measuring the short-circuit current when all of the external sodium was replaced by another cation and, also, by noting the relative degree of inhibition that the alkali metal cations produced on Na influx. The ability of the Group Ia cations to permeate the apical membrane was determined from the tracer uptake experiments. The results demonstrate that (a) only Li and Na are actively transported through the epithelium; (b) the alkali cations K, Rb, and Cs do not enter the epithelium through the apical border and, therefore, Na and Li are the only alkali cations translocated through this membrane; (c) these impermeable cations are competitive inhibitors of Na entry; (d) the cations NH4 and Tl exhibit more complex behavior but, under well-defined conditions, also inhibit Na entry; and (e) the selectivity of the cation binding site is in the sequence Li congruent to Na > Tl > NH4 congruent to K > Rb > Cs, which corresponds to a high field strength site with tetrahedral symmetry. PMID- 6251158 TI - Characterization of Bacillus stearothermophilus plasmid pab124 and construction of deletion variants. AB - A restriction endonuclease cleavage map of the tetracycline resistance plasmid pAB124, originally isolated from Bacillus stearothermophilus, was constructed using ten enzymes. Tetracycline resistance was associated with a 1 x 95 megadalton (Md) region of pAB124 lying between two EcoRI sites, and this region was circularized to produce a viable tetracycline resistance plasmid (pAB224), with two EcoRI fragments of pAB124 deleted amounting to 0 x 95 Md. A second plasmid (pAB524) with one EcoRI fragment (0 x 6 Md) of pAB124 deleted was also constructed. Restriction endonuclease cleavage maps of pAB224 and pAB524 were constructed. PMID- 6251159 TI - The orientation of cytochromes in membrane multilayers prepared from aerobically grown Escherichia coli K12. AB - Centrifugation of membrane vesicles, prepared from ultrasonically disrupted Escherichia coli K12, on to a planar surface followed by slow, partial dehydration results in a high degree of parallel orientation of the membrane planes with respect to each other and the supporting surface. Rotation of such membrane multilayers about a single axis parallel with the membrane planes within the magnetic field of an electron paramagnetic resonance (e.p.r.) spectrometer allows the orientation of anisotropic paramagnetic centres to be deduced. Computer simulations of the angular dependence of cytochrome e.p.r. spectra show two, or perhaps three, cytochromes, well-oriented with respect to the membrane plane. A low-spin cytochrome is oriented with the normal to its haem plane lying in the membrane plane. One (or perhaps two) high-spin cytochrome(s) lies with its haem plane making an angle of 45 degrees with the membrane plane. The orientation of the low-spin cytochrome haem is thus the same as that of haems in b-type cytochromes and cytochrome oxidases of the a type found in the mitochondria of higher animal and microbial cells and the bacterium Paracoccus denitrificans (Erecinska et al., 1979). The possible identity of this low-spin component as the terminal oxidase, cytochrome o, is discussed. PMID- 6251160 TI - DNA restriction and modification in Escherichia coli: functional analysis of the role of the dnaC(D) gene product. AB - Escherichia coli strain PC-7 carries two independent temperature-sensitive mutations, one affecting the restriction and modification (R-M) phenotype and the other the DnaC(D) phenotype. The results of complementation and P1 transduction analysis of the mutation affecting the R-M phenotype implicate a fourth gene, designated hsdX, located close to the hsd three-gene complex. The properties of merodiploids constructed between appropriate recipients and F' elements with different mutations in hsdS, hsdR and hsdM genes might indicate that in strain PC 7 the temperature-sensitive products, determined by hsdR and hsdSK cistrons, are synthesized. The role of the temperature-sensitive dnaC(D) gene product in the formation of the restriction endonuclease was studied and no direct relation was found between the DnaC(D) and R-M phenotypes. PMID- 6251161 TI - Expression of the lactose transposon Tn951 in Escherichia coli, Proteus and Pseudomonas. AB - The control of beta-galactosidase specified by the lactose transposon Tn951 (inserted into RP1 to give pGC9114) has been studied in Escherichia coli K12, Proteus mirabilis, Pseudomonas aeruginosa and Pseudomonas putida; in the first two species comparison could be made with Flac. In E. coli K12, the Tn951 and chromosomally encoded enzymes showed marked qualitative differences in regulatio, the former giving a substantially lower maximum induced level and induction ratio. Several parameters were slightly affected by strain background. In P. mirabilis, beta-galactosidase control determined by both Flac (in accord with earlier work) and pGC9114 was markedly different from E. coli in that maximal induced levels were about an order of magnitude lower and the induction ratio was reduced to 3 to 5. In Ps. aeruginosa and Ps. putida, Tn951-specified lac expression was qualitatively similar to that in P. mirabilis. Possible reasons for anomalous expression in Proteus and Pseudomonas are discussed. PMID- 6251162 TI - Isolation of Escherichia coli mutants (cpdB) deficient in periplasmic 2':3' cyclic phosphodiesterase and genetic mapping of the cpdB locus. AB - Mutants of Escherichia coli deficient in the periplasmic enzyme 2':3'-cyclic phosphodiesterase have been obtained. The gene, designated cpdB, was mapped by conjugation and transduction and found to be located about 0 . 11 min to the right of the cycA locus on the E. coli genetic map. PMID- 6251164 TI - Aminophospholipid asymmetry in murine synaptosomal plasma membrane. PMID- 6251163 TI - Exaggerated norepinephrine-stimulated accumulation of cyclic AMP in vitro in cerebellar slices from pcd mutant mice following Purkinje cell loss. AB - Norepinephrine caused in vitro an accumulation of cylic AMP in slices of the cerebellum from pcd mice which was 300 percent greater than in cerebella from age matched, heterozygous, normal mice. Purkinje cells had disappeared in the pcd mice at the time when the exaggerated hormonal response was seen. The data indicate that high cyclic AMP accumulation can take place in cerebellar cells other than Purkinje cells. PMID- 6251165 TI - Thymidine phosphorylase activity in the optic tectum of developing chick embryos and the effects of 3',5'-cyclic nucleotides and monosodium glutamate on enzyme activity. PMID- 6251166 TI - Multiple alpha 2-noradrenergic receptor sites in rat brain: selective regulation of high-affinity [3H]clonidine binding by guanine nucleotides and divalent cations. PMID- 6251167 TI - Interactions of divalent cations and guanine nucleotides at alpha 2-noradrenergic receptor binding sites in bovine brain mechanisms. PMID- 6251168 TI - Alterations in gamma-aminobutyric acid receptor sensitivity following acute and chronic ethanol treatments. PMID- 6251169 TI - Phosphorylation of synaptic membranes. PMID- 6251171 TI - Norepinephrine-stimulated cyclic AMP formation in rat spinal cord. PMID- 6251170 TI - Partial purification of acid sphingomyelinase from normal and pathological (M. Niemann-Pick type C) human brain. PMID- 6251172 TI - Toxic polyneuropathy due to n-hexane. AB - Three women developed a predominantly motor polyneuropathy following industrial exposure to an adhesive agent containing 80.4% of n-hexane as a volatile substance. Histological and electron-microscopic studies were carried out on sural nerve and on soleus muscle. In the nerve, there were polymorphous changes in both myelin sheaths and axons of large diameter fibres. Irregular and swollen myelin sheaths and segmental swelling of axons with dissolution of neurotubules and evident increase of neurofilaments were frequently observed. Polymorphous inclusion bodies were often present in Schwann cell cytoplasm. The small myelinated and unmyelinated fibres did not show significant changes. The muscles showed denervation atrophy and focal degenerative myopathic changes, with presence of lymphocytic infiltrates and phagocytosis. This study confirms the noxious effect of n-hexane on the peripheral nerve, with development, in our cases, of a toxic polyneuropathy and denervation muscular atrophy with consistent myopathic changes. PMID- 6251173 TI - Cytochrome c oxidase activity and fatty acid oxidation in various types of human muscle. AB - Cytochrome c oxidase activity, carnitine concentration and oxidation rates of pyruvate and palmitate were determined in homogenates of various types of human skeletal muscle. Cytochrome c oxidase activity appeared to be closely related to the pyruvate oxidation rate, but its correlation with palmitate oxidation was less distinct. Trunk muscles oxidize less palmitate and have a lower cytochrome c oxidase activity per mg homogenate protein than leg muscles; soleus muscle biopsies showed higher activities than those of other leg muscles. Based on cytochrome c oxidase activity no large differences are found in palmitate oxidation rate between various types of human muscle. Cytochrome c oxidase activity and palmitate oxidation rate of muscles do not show an age dependency. The carnitine concentration is similar in all kinds of human skeletal muscle. PMID- 6251174 TI - A new type of hereditary distal myopathy with characteristic sarcoplasmic bodies and intermediate (skeletin) filaments. AB - A family with a hitherto unrecognized type of distal myopathy is described. The disorder appears to be of late onset and to be inherited through a dominant autosome. It has a more malignant course than the distal myopathies described earlier, from which it can be differentiated clinically by an early involvement of thenar muscles and hand flexors. The key to the correct diagnosis is provided by the morphological and immunohistological investigation of muscle biopsies, which show typical sarcoplasmic bodies and an abundance of intermediate-sized (skeletin) filaments. PMID- 6251176 TI - Detection of uremic neuropathy by reflex response latency. AB - Dialysis time necessary for treatment of terminal renal failure is very different in different patients. Adequacy of therapy cannot be controlled by laboratory measures but only clinical means. Uremic peripheral neuropathy is regarded as the most reliable indicator of insufficient dialysis treatment. Serial measurements of peripheral nerve function therefore make individual adjustment of dialysis schedule possible. In some cases motor nerve conduction velocity is not sensitive enough for this purpose, as conduction velocity in afferent nerve fibers is disturbed at an earlier stage of uremic intoxication. Measurement of sensory nerve conduction velocity is time consuming and afferent fibers can also be examined in proprioceptive reflexes. Ths suitability of H-reflex response latency (RRL) for detection of slight uremic neuropathy was analysed. The wide range of RRL in healthy subjects can be explained by the different length of neural pathway in different subjects. A strong correlation between RRL and body height was found in healthy subjects. Relating RRL to the body height gives a highly sensitive measure of peripheral nerve function. Asymptomatic uremic neuropathy was detected very much earlier by RRL than by motor nerve conduction velocity. The method proved to be well suited for routine monitoring of uremic neuropathy in patients on dialysis. PMID- 6251175 TI - Specificity of biophysical and biochemical alterations in erythrocyte membranes in neurological disorders--Huntington's disease, Friedreich's ataxia, Alzheimer's disease, amyotrophic lateral sclerosis, and myotonic and duchenne muscular dystrophy. AB - Previous studies in our laboratory had demonstrated alterations in the physical state of membrane proteins in erythrocytes in Huntington's disease. In order to assess the specificity of our findings, the results of electron spin resonance studies of protein and lipid components, scanning electron-microscopic studies, enzymatic analyses of membrane-bound sodium plus potassium stimulated, magnesium dependent adenosine triphosphatase and protein kinase, and cell deformability studies of erythrocyte membranes have been performed in the neurological disorders, Huntington's disease, Friedreich's ataxia, Alzheimer's disease, amyotrophic lateral sclerosis, and myotonic and Duchenne muscular dystrophy. Comparison of the results revealed that alterations in the biophysical and biochemical states of erythrocyte membranes in each disorder are specific to the particular disease state with the exception of those in Friedreich's ataxia and Alzheimer's disease. In the latter instance, the clinical and pathological alterations suggest that these two diseases have different primary defects. Our studies suggest that the molecular basis of each disease is different. In addition, the results suggest that biophysical and biochemical investigations of extraneural tissue in Huntington's disease and other neurological disordes have the potential of clarifying the molecular mechanisms by which these diseases arise. PMID- 6251177 TI - Inhibition of mechanosensory interneurons in the crayfish. I. Presynaptic inhibition from giant fibers. AB - 1. Sucrose-gap and intracellular recordings were used to study the primary afferent depolarization (PAD) produced in mechanosensory afferents by impulses in lateral and medial giant axons, which are the command cells for the tail flip escape response in the crayfish. 2. The lateral and medial giant axons produce PAD through a polysynaptic interneuronal pathway. The response has a relatively long intraganglionic latency (7--11 ms), and command-evoked PAD can be recorded in ganglia from which the giant axons have been experimentally disconnected. 3. The final neurons of the pathway that delivers inhibition are few in number and extensive in distribution; most appear to be common to lateral and medial giant pathways. 4. At least some of the inhibitory interneurons have axons in the interganglionic connectives and probably produce both presynaptic and postsynaptic inhibition. 5. Stimulation of the lateral, but not the medial, giant axons causes a small, short-latency deplorization that is stable at high repetition rates. This small potential can be accounted for by transmission across known electrical synapses between mechanosensory afferents and the lateral giants in each abdominal ganglion. 6. Repetitive stimulation of the lateral giant axons causes substantial augmentation of PAD, apparently through recruitment of additional interneurons. PAD evoked by a single medial giant (MG) stimulus is generally much larger than that elicited by a single lateral giant (LG) spike. However, MG-PAD summates little and so the maximum PAD deltaV reached during repetitive firing is equivalent for the two types of giant axons. 7. Iontophoresis of gamma-aminobutyric acid (GABA) into the ganglionic neuropil depolarizes the primary afferents and blocks activity in neurons that have axons in the interganglionic connective. 8. The extrapolated PAD reversal potential and pharmacological studies suggest that a GABA-mediated chloride conductance increase is involved in the production of PAD. PMID- 6251178 TI - On- versus off-responses of raccoon glabrous skin rapidly adapting cutaneous mechanoreceptors. AB - 1. The on- and off-responses of 50 raccoon median nerve fibers associated with rapidly adapting cutaneous mechanoreceptors in glabrous skin were examined under experimental conditions designed to allow comparable opportunities for on- and off-responses to occur. Trapezoidal stimuli were utilized, providing for equal stimulus indentation and retraction velocities and equal static displacement times and intertrial intervals. Principal findings were as follows: 2. At stimulus levels well above displacement and velocity thresholds for on-responses, 80% of units yielded a more vigorous on-response than off-response (as measured by the total number of ramp impulses); in 6%, the reverse was true; while in the remaining 14%, the off-discharge was absent. 3. On and off displacement thresholds were approximately equal (on median, 43 micron; off median, 42 micron). However, on velocity thresholds were significantly lower than off velocity thresholds (on median, 1.0 micron/ms; off median, 3.8 micron/ms). 4. Exponents (b) of power functions relating discharge rate to ramp velocity (frequency = a x velocityb) were consistently greater for on-responses than for off-responses, but intercept constants (a) were consistently greater for off responses than for on-responses. 5. Previous findings that mammalian rapidly adapting (RA) mechanoreceptors possess a "linear directionality" generally favoring on-responses were confirmed. 6. Results are discussed in relation to the role of viscoelastic properties of RA mechanoreceptors and neighboring skin. It is suggested that, when considerations is also given to the mechanical properties of surrounding tissues, the Loewenstein and Skalak (18) analysis of the mode of operation of Pacinian corpuscles might also apply, at least qualitatively, to the simple dermal (rapidly adapting) corpuscle of raccoon glabrous skin. PMID- 6251179 TI - Inhibition and excitation of primate spinothalamic tract neurons by stimulation in region of nucleus reticularis gigantocellularis. AB - 1. Electrical stimulation in the region of the nucleus reticularis gigantocellularis (NGc) in anesthetized monkeys inhibited or excited spinothalamic tract neurons in the lumbosacral and cervical enlargements. 2. The descending effects were generally more pronounced for activity evoked by cutaneous A-delta-fibers than for activity produced by large myelinated cutaneous afferents. Nevertheless, the responses to all types of natural stimuli used could be inhibited or facilitated. 3. The excitation from repeated brief stimulus trains to the NGc sometimes increased progressively, suggesting the existence of a positive feedback system. Occasionally, repeated stimulation of the NGc produced a progressively greater inhibition. 4. The threshold stimulus strength to elicit the inhibitory and excitatory actions was usually less than 50 microA, and in some cases less than 25 microA. The inhibition and excitation increased as the stimulus intensity was raised above the threshold value, or as the number and/or frequency of pulses in the stimulus train was increased. 5. The strongest inhibition and excitation was produced by stimulation within the NGc on either side of the brain stem. There was no obvious topographic organization of inhibitory and excitatory zones. 6. Dorsolateral tractotomies in the high cervical spinal cord did not prevent the effects of NGc stimulation, indicating that the inhibitory and excitatory pathways descend in the ventral parts of the white matter. 7. It is suggested that the inhibition and excitation are mediated by the medullary reticulospinal system. PMID- 6251180 TI - Properties of a persistent inward current in normal and TEA-injected motoneurons. AB - 1. Membrane currents of normal and TEA-injected cat lumbar motoneurons were investigated using the technique of somatic voltage clamp. 2. The current-voltage (I-V) relation of healthy motoneurons contains a region of negative slope conductance caused by a persistent inward current component (Ii). In the most striking examples, Ii is net inward at some potentials between 10 and 30 mV positive to resting potential. 3. Near its activation threshold (greater than or equal to 10 mV positive to rest), Ii does not decrement during prolonged voltage steps and, in most cells, activates very slowly. Ii amplitude increases and time to peak Ii decreases with further small increments of depolarization, and Ii decrements during sustained voltage steps. Maximum Ii amplitude occurs 20--30 mV positive to rest in most cells. Ii is not visible at sufficiently large depolarizations. 4. Ii appears to be mixed with potassium current components at nearly every potential where it is visible. These include a slow outward current first activated near Ii activation threshold, a fast outward current additonally activated at larger depolarizing potentials, and a fast, transient outward current that obscures the true onset of Ii at nearly every potential. 5. Ii is not carried by sodium entering via the fast, transient channels and is present after pharmacological blockage of sodium currents. It is proposed that Ii is predominantly carried by calcium ions. 6. The presence of inward tail currents after repolarization from potentials that activate a steady outward current suggest that Ii remains present but hidden at large depolarizations. Ii inactivation was further investigated in TEA-injected motoneurons since Ii and the tail currents are more prominent in these cells. 7. Conventional recordings from TEA-injected motoneurons suggest that a prolonged, postspike plateau potential is maintained by a persistent inward current. Voltage-clamp data can account for the principal features of the plateau potential. 8. Voltage-clamp results in TEA-injected motoneurons suggest that Ii is subject to little or no inactivation at potentials less than or equal to 30 mV positive to rest and to partial inactivation, at most, at higher potentials during steps lasting less than or equal to 100 ms. The apparent decay of Ii during sustained depolarization is caused by the development of a larger outward current. 9. Ii is similar in several ways to a persistent calcium current observed in some molluscan neurons. Theoretical and experimental results suggest that Ii is generated predominantly in a local region under voltage control and that the observed membrane currents govern somatic membrane potential and cell behavior. PMID- 6251181 TI - Neurodynamic response analysis of anterior semicircular canal afferents in the pigeon. AB - 1. The neurodynamic responses to sinusoidal and pulse angular accelerations were studied in anterior semicircular canal afferents in the barbiturate-anesthetized pigeon. 2. The resting discharge frequency, aS, varied from 7.4 to 149.0 impulses/s. For most units, aS remained fairly constant for long periods of time during the experiment. 3. The neural-response harmonic distortion, resulting from stimulation by sinusoidal angular accelerations, varied in different units. Percent distortions from as low as 3% to those as high as 57% were determined. 4. Intensity-function plots of peak first harmonic neural response as a function of the peak sinusoidal angular acceleration (with frequency, f, as a parameter) are of two types: one has a linear relationship between the variables; the other demonstrates pronounced nonlinearities ("saturation," particularly for low values of f). In saturation-type units, the data of which fit a power law function, the exponent of the function is frequency dependent, becoming closer and closer to unity with increasing f. 5. Data for all units fit the transfer function, G'(s) = Csk/(tauLS + 1), where G'(s) relates the unit response to angular acceleration, C is a gain constant, 0 < k < 1, and tauL is the so-called long time constant of the classical torsion pendulum model. tauL varied from 4.45 to 22.17 S (mean +/- SE = 10.24 +/- 1.20 S). This may be interpreted as an indication of a regional distribution of tauL'S within the neuroepithelium. Arguments are advanced to show that this is consistent with our present understanding of the ampullary end organ. 6. The degree of regularity of the spontaneous discharge (as determined by the coefficient of variation, CV) was significantly correlated with the parameter k in G'(S). The larger the CV, the larger is the corresponding k. Further work indicated that the larger the value of k, the more adaptation a unit exhibited (k varied from 0.017 to 0.66). 7. The time-domain response of G(S) = G'(S)/(tauSS + 1) to different durations of pulse angular acceleration stimuli agreed well with the neural response to these stimuli (tauS = 2.27 ms is the short time constant of the torsion pendulum model). 8. The term Sk was decomposed into an expression containing a series of polynomials in S in the numerator and denominator. The first term in this expansion K0tau1S/(tau1S + 1), has previously been shown to describe so-called adaptation properties in the dynamics of the semicircular canals. A mean (+/-SE) tau1 = 71.56 (+/-10.01) S was determined. Evidence is presented that Sk probably represents a relaxation phenomenon comprised of a time varying intracellular Na+/K+-transport process, components of which are summed with the generator potential in the afferent terminal(S) of the receptor hair cell. PMID- 6251182 TI - Sensory discrimination: decision process. AB - 1. This paper and a following paper deal with problems, such as the following, that arise in experimental studies of the neural mechanisms underlying sensory discrimination: What measures of neural activity are relevant in such a study? How can sample data from the responses of single neurons be combined to represent the information relayed by a population of neurons? How can neural data be compared with results from psychophysical studies? What assumptions are implicit in any such comparison? What are the implications of assumptions that neurons respond independently or that they have homogeneous response properties? How can neural codes be assessed in a systematic way? Can psychophysical and neurophysiological observations be combined to infer mechanisms or relationships in the processes underlying discrimination? All of these questions require some theoretical framework before they can be answered. These papers set out such a framework, they deal with most of those questions, and they provide practicable formulas for relating sample data from neurophysiological experiments to behavioral measures derived from psychophysical experiments. 2. The processes that intervene between a relatively peripheral array of neural activity and a subject's decision in a discrimination task are split into two sections: a) the ascending sensory processes that provide the final patterns of neural activity on which discrimination is based, and b) a process that yields decisions of the type required by the experimental design used in the psychophysical study. The approach is to develop a theory of the decision process in this paper, and then to expand it to incorporate the ascending processes in the following paper. 3. The decision theory deals with a class of experimental designs in which a subject is required to make a decision about two stimuli S1 and S2 (e.g., S1 is larger than S2, S2 is the same as S1, S2 was the modified stimulus, and so on). A mathematical representation for experimental designs of this type is developed. 4. The decision process is analyzed in two forms: a) a multivariate form in which the discrimination decision results directly from multidimensional neural representation of the two stimuli, and b) a vivariate form in which the final representation of each stimulus is a unidimensional variable. Conditions required for equivalence of these formulations are examined. 5. The theory includes as explicit variables a) the experimental design, b) the subject's discrimination strategy, c) bias, d) memory variance, e) bias variance, f) variance in the final neural representations of the stimuli, and g) their functional dependence on the stimuli that they represent. 6. Formulas are developed for the expected values of commonly used psychophysical measures such as the classical psychometric function, receiver operating characteristic (ROC) functions, discriminatory separation index (d'), and the difference limen. 7. Optimum discrimination behavior is analyzed. PMID- 6251183 TI - Multiple sclerosis, adrenocorticotropic hormone, and nursing implications. PMID- 6251184 TI - Differential accumulation of Tc-99m DTPA and Tc-99m pyrophosphate within cerebral and cranial lesions: concise communication. AB - We sought to determine the clinical utility of using a bone-scanning agent in addition to a brain-scanning agent for the imaging of cerebral and cranial lesions. Images were obtained in 51 patients with Tc-99m diethylene-triamine pentacetic-acid (DTPA) followed by Tc-99m pyrophosphate (PPi) within 2--5 days. The scans were qualitatively analyzed and the lesion-to-background count density ratios were determined from the corresponding brain and skull images. Only four of 20 cerebral infarctions were better demonstrated with PPi, whereas they were better with DTPA in 14 patients. They were equally good in two patients. The average lesion-to-background count-density ratio for infarction was 1.555 +/- 0.335 with DTPA and 1.428 +/- 0.573 with PPi (p < 0.05). Primary brain tumors were better visualized with DTPA in four out of five cases (p < 0.05). Metastases to brain showed up better with DTPA in 15 of 16 patients (p < 0.05), whereas all ten metastases to skull were seen better with PPi (p < 0.01). These results support previous reports regarding the radiopharmaceutical of choice for tumor imaging but not for infarction. This may be due to the differences in blood clearance for the various imaging agents. PMID- 6251185 TI - Effect of dietary fiber on mineral absorption in growing rats. AB - The effect of "indigestible" polysaccharides fed at the 10% level in a semi synthetic diet on absorption of Ca, Fe, Zn, Cu, Cr and Co, on weight gain and on fecal dry matter excretion was studied over a period of 8 days in five groups of 12 weanling male rats each and compared to a control group. Carrageenan (C) and agar-agar (AA) reduced absorption of all minerals tested, Na-alginate (NA-A) decreased Fe-, Cr- and Co-absorption, carob bean gum (CBG) and gum guar (GG) interfered with the absorption of Zn, Cr, Cu and Co. In a second study the long term effect of GG and AA-ingestion at the 10% dietary level on mineral absorption was investigated during three 4-day balance periods of a 21-week feeding trial in 24 young rats. Mineral content of rat carcasses, assayed at the termination of the experimental period, did not reveal any significant differences between controls and animals fed AA or GG, suggesting that the rat is able to compensate for the increased fecal losses, presumably by reduced urinary losses. Ingestion of AA, C or Na-A resulted in a marked increase of fecal dry matter, indicating that hardly any of these substances were degraded, whereas a considerable portion of GG and CBG was metabolized, presumably due to the action of intestinal bacteria. PMID- 6251187 TI - Use of deuterium oxide for the in vivo prediction of body composition in female rats in various physiological states. AB - Deuterium oxide (D2O) was used to estimate total body water (TBW) and subsequently to predict the body composition of female rats at breeding, after pregnancy and after lactation as influenced by dietary manipulation. The correlation between D2O space (grams) and body water (grams) was 0.893 (P < 0.01). Deuterium oxide space accounted for 70% of the variance in predicting the weight of TBW. Fixed effects (pregnancy, lactation, feeding levels and two-way interactions) accounted for an additional 10% (P < 0.05) of the variance. The correlation between TBW in grams (predicted from D2O space, grams) and total body protein (grams) was 0.700 (P < 0.01). Total body water accounted for 49% of the variance in total body protein. Fixed effects accounted for an additional 21% (P < 0.05) of the variance in total weight of body protein. The correlations between D2O space (%) and body water (%) and between D20 space (%) and body fat (%) were 0.786 (P < 0.01) and -0.758 (P < 0.01), respectively. The accuracy of estimation of body water (%) and body fat (%) from D2O space was not significantly improved (P > 0.05) when the fixed effects (pregnancy, lactation, feeding levels and two way interactions) were included in the model. PMID- 6251186 TI - Effect to cholecalciferol and 1,25-Dihydroxycholecalciferol on the intestinal absorption of zinc in the chick. AB - The effect of cholecalciferol on the intestinal absorption of 65Zn was assessed in zinc-deficient and zinc-replete rachitic chicks, using the in situ ligated loop techniques. Cholecalciferol did not significantly affect 65Zn absorption in either group, although the synthesis of the intestinal calcium-binding protein (CaBP) in both groups was similar. In an analogous study, 1,25 dihydroxycholecalciferol increased 47Ca absorption and induced the synthesis of CaBP but exerted on effect on 65Zn absorption in zinc-deficient rachitic chicks. When fed a diet adequate in cholecalciferol, more CaBP was present in the intestine of the zinc-adequate group than in the zinc-deficient group, possibly due to the greater rate of growth and therefore the greater need for calcium by the former group. These results suggest that cholecalciferol and its most active metabolite do not directly affect zinc absorption and, by inference, that the vitamin D-dependent transport mechanism is not involved in zinc homeostasis, or in the interaction between calcium and zinc. PMID- 6251188 TI - Competence of 1 alpha, 25-dihydroxyvitamin D3 receptor system in embryonic chick intestine. PMID- 6251189 TI - The use of the optacon as a screening device. A new technique for detecting sensory loss in individuals exposed to neurotoxins. AB - Periphral neuropathy is one of the most common nervous system reactions to toxic chemicals. Early detection signs of peripheral neuropathy among workers exposed to these chemicals is of paramount concern to occupational physicians. This study describes the use of the Optacon to to assess finger-tip sensation in normal and diabetic subjects. The instrument is capable of detecting the steady increase in threshold with age and is able to identify peripheral neuropathy in diabetic subjects. There was little variation upon repeated testing of the same subject. This study illustrates the usefulness of the Optacon as as a simple, reliable technique for detecting sensory loss in individuals with peripheral neuropathy, and suggests that it may be useful in detecting sensory loss in workers exposed to neurotoxins. PMID- 6251190 TI - Molluscum contagiosum of the lower lip: report of a case. PMID- 6251191 TI - Recurrent melanotic neuroectodermal tumor of infancy: report of case and tumor heterotransplantation studies. AB - A fifth case of rapidly recurring melanotic neuroectodermal tumor of infancy is reported. The possibility of recurrence and subsequent encroachment on vital facial structures is emphasized. Vigorous bony curettage at initial excision of this benign lesion may aid in the preventing recurrence. Heterotransplantation studies disclosed the benign nature of the MNTI cells. PMID- 6251192 TI - [Facial paralysis and varicella-zoster virus (VZV); fluctuations in anti-VZV antibody titers and early diagnosis by viral specific IgM antibody examination (author's transl)]. PMID- 6251193 TI - Renal prostaglandin E2 in nephrogenic diabetes insipidus: effects of inhibition of prostaglandin synthesis by indomethacin. PMID- 6251194 TI - Management of bilateral diffuse nephroblastomatosis. PMID- 6251195 TI - Ocular abnormalities in chronic familial hyperphosphatasemia. AB - The ocular findings in two patients with Chronic Familial Hyperphosphatasemia are described in detail. They consist mainly of abnormal pigmentation, the presence of retinal folds of variable degree, and angioid streaks. It is suggested that these changes are in relationship to abnormal collagen metabolism and that CHF is not only a bone dysplasia but a more generalized condition with variable extraskeletal manifestations. PMID- 6251196 TI - Preoperative chemotherapy for hepatoblastoma in children: report of six cases. AB - Surgical excision has been the primary treatment for hepatoblastoma; however, at presentation, only one-third of such tumors are surgically resectable. Without operation, the disease is universally fatal. Six children with initially unresectable hepatoblastoma (two with pulmonary metastases) were treated with chemotherapy, which included Adriamycin. Four of the six children showed a significant reduction in tumor size, in three delayed resection of the primary lesion was possible, and the fourth patient died of Adriamycin cardiotoxicity. Two patients did not respond and developed pulmonary metastases after 2 and 16 mo of chemotherapy, respectively. Adriamycin alone, or in combination with other agents, has proven effective in primary and metastatic childhood hepatoblastoma. This preoperative chemotherapy regimen permits resection of previously unresectable hepatoblastoma at "second look" operation and reduces the morbidity and mortality of an otherwise extensive operation. PMID- 6251197 TI - Carbocyclic analogs of arabinosylpurine nucleosides. AB - Carbocyclic analogs of arabinofuranosylguanine (VII) and 2,6-diamino-9-beta arabinofuranosylpurine (VIII) and the corresponding 8-azapurine analogs, 5-amino 7-hydroxy-3-[2 alpha,3 beta-dihydroxy-4 alpha-(hydroxymethyl)cyclopent-1 alpha yl]-v-triazolo[4,5-d]pyrimidine (X) and 5,7-diamino-3-[2 alpha,3 beta-dihydroxy-4 alpha-(hydroxymethyl)cyclopent-1 alpha-yl]-v-triazolo[4,5-d]pyrimidine (XI), were prepared. Carbocyclic nucleoside analogs VII and X exhibited significant cytotoxicity against P-388 mouse leukemia cells in culture. In vitro testing against herpes simplex type 1 (strain HF) indicated that only VIII exhibited significant antiviral activity. PMID- 6251198 TI - Anti-inflammatory activity of amine cyanoboranes, amine carboxyboranes, and related compounds. AB - Amine cyanoboranes and amine carboxyboranes (boron analogs of alpha-amino acids) were shown to inhibit inflammation. The analogs effectively blocked general inflammation, induced arthritis, and the writhing reflex associated with inflammation pain, while the inflammation associated with pleurisy was marginally inhibited. The boron analogs were shown in vitro to inhibit the release of lysosomal enzymes from liver and polymorphonuclear neutrophils. Furthermore, prostaglandin synthesis was blocked by these agents at a low concentration, i.e., 10(-6) M. Liver oxidative phosphorylation processes also were uncoupled by these agents, but the migration of polymorphonuclear neutrophils was unaltered at 10( 4) M. The elevation of cyclic adenosine monophosphate levels in polymorphonuclear neutrophils correlated positively with in vivo antiarthritic activity. Initial studies in rodents demonstrated that these boron analogs can be used at safe therapeutic doses. PMID- 6251199 TI - Stability of solid drugs: degradation of ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3) at high humidities and elevated temperatures. AB - Ergocalciferol and cholecalciferol powders were studied at 25 and 40 degrees and at different humidities. Ergocalciferol decomposed rapidly at 25 and 40 degrees when stored in dry air. Decomposition of ergocalciferol led to the formation of products of higher polarity. Cholecalciferol was not as labile under dry conditions, but decomposed rapidly at high temperature. PMID- 6251200 TI - Alpha-drenergic inhibition of calcium-dependent potentials in rat sympathetic neurones. AB - 1. Post-ganglionic neurones of the rat superior cervical ganglion were studied in vitro (21-26 degrees C) using single intracellular micro-electrode methods. 2. Three Ca2+-dependent potentials were studied: the shoulder on the normal action potential, the hyperpolarizing afterpotential (h.a.p.), and th Ca2+ spike. 3. Bath-applied noradrenaline reversibly inhibited these Ca2+-dependent potentials. The EC50 for inhibition of peak h.a.p. amplitude was about 1 microM. The order of catetholamine potency was: L-adrenaline > L-noradrenaline > D-noradrenaline congruent to dopamine > DL-isoprenaline. Phentolamine (10 microM), an alpha blocker, but not MJ-1999 (10 microM), a beta-blocker, antagonized the action of noradrenaline. 4. Noradrenaline (10 microM) hyperpolarized most neurones (1-6 mV) studied, with no detectable change in resting membrane conductance. 5. Superfusion with low external Ca2+ and high Mg2+ mimicked the effect of noradrenaline. Either procedure alone antagonized the h.a.p. conductance increase but did not alter the h.a.p. reversal potential. However, in the presence of low Ca2+, high Mg2+, the remaining action potential and h.a.p. were not further reduced by noradrenaline. 6. The Ca2+-dependent shoulder of the action potential did not appear dependent upon GK. Noradrenaline and low Ca2+ antagonized the shoulder when enhanced by TEA+ or Ba2+. 7. Both the rate of rise and amplitude of the Ca2+ spike were antagonized by noradrenaline. 8. We propose that activation of an alpha-adrenoceptor inhibits a voltage-sensitive Ca2+ conductance (GCa(V)), thereby reducing the inward Ca2+ current which may generate the noraml action potential shoulder and the rising phase of the Ca2+ spike. Reduction of Ca2+ current would also reduce the Ca2+-dependent portion of outward K+ current underlying the h.a.p. PMID- 6251202 TI - Mouse pancreatic acinar cells: effects of electrical field stimulation on membrane potential and resistance. AB - 1. Intracellular micro-elctrode recordings of acinar cell membrane potential and resistance were made from the mouse pancreas superfused in vitro. The acinar cells under investigation were stimulated by electrical field stimulation using two platinum wire electrodes and by micro-ionophoretic acetylcholine (ACh) application from an extracellular AChCl-filled micro-electrode. 2. Field stimulation evoked membrane depolarization and reduction in input resistance. Maximal effects were observed at 20-40 Hz frequency, 1-2 msec pulse width and 8 20 V amplitude. The mean latency for the field stimulation-evoked depolarization was 900 msec. Field stimulation responses were seen at low frequency levels of stimulation, the majority of cells responding at 5 Hz and some at 2 Hz. The physiological significance of the low frequency stimulation is discussed. 3. The field stimulation effects resembled those induced by ACh ionophoresis and were abolished by atropine. The equilibrium potentials for both field stimulation and ACh ionophoresis were identical at about -15 mV. The field stimulation response was selectively abolished by tetrodotoxin and by superfusion with Na-free or Ca free media, while the ACh ionophoretic response persisted. Field stimulation therefore initiated nerve action potentials and consequent ACh release. 4. Spontaneous miniature depolarizations observed in some preparations were not abolished by tetrodotoxin and woult therefore seem to be a result of quantal release of ACh from nerve terminals. 5. There is no indication from the present studies of the existence of neurotransmitters other than ACh. No inhibitory effects have been observed. 6. All preparations studied to date have responded to field stimulation and it is concluded that all acinar cells are potentially under cholinergic neural influence. PMID- 6251201 TI - Characteristics of histamine release evoked by acetylcholine in isolated rat mast cells. AB - 1. Histamine secretion from rat mast cells occurs in the presence of nanomolar concentrations of acetylcholine. 2. Intact glycolytic and oxidative metabolism is required for the acetylcholine-induced histamine secretion. Removal of extracellular glucose, hypoxia, cyanide and monoiodoacetate almost completely inhibit the secretion. 3. The secretion of histamine is dependent on the extracellular H ion concentration and is blocked when the cells are exposed to Na deficient media. 4. The order of potency of cholinrgic agonists in evoking the secretion of histamine is oxotremorine > acetylcholine > choline > carbamycholine > nicotine. 5. Atropine competitively blocks the acetylcholine-induced histamine secretion, indicating the presence of cholinergic muscarinic receptors on mast cells. 6. Dibutyryl cyclic AMP and adrenaline inhibit the acetylcholine-induced histamine secretion, indicating a regulatory function afforded by cyclic nucleotides in the cholinergic histamine release. PMID- 6251205 TI - [Experimental neuroendocrinology. 10th annual meeting of the French Society of Experimental Neuroendocrinology, Oullins, 6-7 September 1979]. PMID- 6251203 TI - The effects of vanadate on the fluxes of sodium and potassium ions through the sodium pump. AB - 1. The effects of sodium orthovanadate on the fluxes of sodium and potassium (or rubidium) ions through the sodium pump have been investigated in intact human red cells and in resealed ghosts prepared from them. Sodium-potassium exchange, potassium-potassium exchange, pump reversal, sodium-sodium exchange and uncoupled sodium efflux have each been studied.2. When intact human red cells were incubated in high-sodium media containing vanadate in low concentrations, inhibition of potassium or rubidium influx was marked only if the potassium or rubidium concentration in the medium was sufficiently high to cause nearly maximal influx in the absence of vanadate. The absence of inhibition at lower potassium or rubidium concentrations cannot be explained by supposing that the onset of inhibition by vanadate is slower in these conditions.3. Lowering the extracellular sodium concentration, or raising the vanadate concentration, decreased the minimum concentration of extracellular potassium or rubidium at which inhibition by vanadate was detected.4. Experiments on potassium influx into intact red cells treated with the ionophore A23187 showed that magnesium ions act at intracellular sites to promote inhibition by vanadate.5. Measurements of potassium efflux from intact red cells incubated in high-sodium media, with or without potassium, showed that potassium-potassium exchange was inhibited by vanadate at low concentrations whereas reversal of the pump was not.6. Measurements of sodium efflux from intact red cells or resealed ghosts incubated in high-sodium media, with or without potassium, showed that vanadate had little or no effect on sodium-sodium exchange at concentrations at which sodium potassium exchange was markedly reduced. Much higher concentrations of vanadate did cause partial inhibition of sodium-sodium exchange.7. Experiments to determine whether vanadate in low concentrations inhibited uncoupled sodium efflux were inconclusive, but suggested that the flux was inhibited. Measurements of the ATP hydrolysis that is thought to be associated with the uncoupled sodium efflux showed that this hydrolysis was strongly inhibited.8. The different effects of vanadate on the different fluxes are discussed, and related to the way in which vanadate is thought to act on the sodium pump. PMID- 6251204 TI - Electrical properties of individual cells isolated from adult rat ventricular myocardium. AB - 1. Individual cells were isolated from adult rats ventricular myocardium by a collagenase digestion procedure. 2. Steady membrane potentials recorded with conventional intracellular glass micro-electrodes from cells in a modified Krebs solution containing 3 . 8 mM-KCl and 0 . 5 mM-CaCl2 were less negative than -40 mV in most cells (-25 . 3 +/- 10 . 9 mV, mean +/- S.D., 211 cells). 3. After addition of the potassium selective ionophore valinomycin (60 nM) to the bathing solution all recorded membrane potentials were more negative than -60 mV (-74 . 8 +/- 7 . 0 mV, sixty-three cells). 4. The internal concentration of potassium in the cells was determined as 120 . 8 +/- 1 . 7 mM (+/- S.E., n = 24) by flame emission spectrometry after centrifugation through silicone oil, using tritiated water and D-[1-14C] mannitol to estimate total and extracellular water in the pellet. 5. In the majority of cells in the standard solution the membrane potential recorded within a few msec of penetration was more negative than -70 mV (-78 . 4 +/- 9 . 7 mV, seventy-three cells). In sixty-six cells penetration initiated an action potential which overshot zero by 31 . 3 +/- 7 . 1 mV. This overshoot was abolished by reducing the external sodium to 0 . 1 of the normal value, and reduced or abolished by addition of tetrodotoxin (30 microM). 6. Modifications of the standard bathing solution which increased the number of cells with steady recorded membrane potentials more negative than -60 mV were: isosmotic substitution of sucrose for NaCl; replacement of NaCl and KCl by sodium isethionate and potassium methyl sulphate; addition of 5 or 10 mM-CaCl2; addition of 10 mM-MnCl2. 7. For cells in solution containing 2 . 5 or 5 . 5 mM-CaCl2, input resistances estimated from the amplitude of hyperpolarizations evoked by 200 msec current pulses were approximately 40 M omega at a resting potential close to -80 mV and became much greater as cells were depolarized. Time constants measured at the resting potential were approximately 8 msec. 8. In certain conditions, repeated spontaneous action potentials were recorded from contracting cells, and in quiescent cells evoked action potentials could be initiated by applying brief depolarizing pulses through the micro-electrode. Action potentials were coincident with contractions. 9. It is concluded that the resting potential of these isolated cells is normally more negative than -70 mV, and that the cells retain the ionic mechanisms necessary for the generation of active currents. PMID- 6251206 TI - [Basic principles for characterization of hormonal membrane receptors. Application to assay methods (author's transl)]. AB - Basic calculations for membrane receptor characterization, concentration and the affinity constant, are given including usual data linearization procedures. Determination of the specific radioactivity and maximum binding activity of the tracer and development of saturation curves from binding-inhibition experiments together with criteria for correction of non-specific binding, are presented both theoretically and practically in giving examples from the author's study of Luteinizing hormone (Lutropin) receptors in boar testis. The interest for physiologists of the receptor characterization is emphasized by underlying the regulatory aspect in hormone response of the variation of receptor concentration at the target cell surface in the case of spare receptors. PMID- 6251207 TI - [Hypophyseal GnRH receptors. A minireview (author's transl)]. AB - The preliminary step in the involvement of gonadoliberin (GnRH) in the cellular mechanism for the secretion of the gonadotropic hormones LH and FSH, consists of a reversible binding of GnRH with specific site on plasma membranes of the pituitary gland. The parameters of this interaction have been determined in vitro with the aid of biologically active preparations of synthetic GnRH labelled with [3H] or [125I], and homogenates or preparations of plasma membranes, from the pituitary glands, of rat, sheep or beef. According to several authors, one or two types of sites are involved in GnRH-receptor binding. At 0-4 degrees C, the equilibrium association constants of the high affinity sites vary from 0.77 X 10(8) M-1 to 2.33 X 10(10) M-1. At 37 degrees C, we have obtained a value of 1.1 X 10(8) M-1 for this constant. Low affinity binding sites have been found in pituitaries and in other tissues; according to CLAYTON (1979), they may be structurally bound to enzymes which degrade GnRH. Other authors feel that a correlation may exist between the biological activity of agonistic analogues of GnRH and their capacity for binding to high affinity sites. Modulation of the binding of GnRH to low and high affinity sites by steroids and/or peptidases has been considered. The existence of intracellular receptors and internalisation of the GnRH-receptor complex have also been reported. PMID- 6251208 TI - [Pituitary LHRH receptor sites: quantification with a superactive analog as tracer, structure-function relationship, and change during castration in male rats (author's transl)]. PMID- 6251209 TI - [Specificity of the effect of vasopressin at the anterior pituitary level (author's transl)]. AB - The present investigation was conducted in order to get more insight into the mechanism of action of vasopressin (VP) on ACTH secretion and characterize VP interaction with putative receptor sites at the level of the anterior pituitary gland. The experimental procedure consisted of increasing ACTH release from incubated pituitary fragments as induced by VP in the presence or absence of oxytocin (OT) and various releasing factors. Our results show that, whereas OT was able to depress VP-induced release of ACTH (Fig. 2), TRF (Fig. 3), LH-RH (Fig. 4) and crude "CRF" extract (Fig. 1) it did not exhibit any significant inhibitory effect. This provides indirect evidence for the presence of specific pituitary sites for VP and related peptides such as OT. The latter, however, was devoided of corticotrophic releasing properties. PMID- 6251210 TI - [Bioactive and immunoreactive molecular forms of adrenocorticotropic hormone in the fetal rat hypophysis (author's transl)]. PMID- 6251211 TI - [Cardiac electrogenesis]. PMID- 6251212 TI - Melancholy in the 20th century: causes and prevention. PMID- 6251213 TI - Operation: homeward bound--a military psychiatric transition program. PMID- 6251214 TI - Helping students to resolve conflicts between their religious beliefs and psychiatric-mental health treatment approaches. PMID- 6251215 TI - A comprehensive adolescent treatment program: an inpatient, interdisciplinary approach. PMID- 6251216 TI - Immunological parameters in gestational trophoblastic neoplasia. AB - Immunological function were studied in 22 patients with hydatidiform mole and 29 patients with malignant trophoblastic disease before and after treatment; normal pregnant and post-pregnant women served as controls. The only significant abnormality in hydatidiform mole was a low granulocyte chemotaxis before evacuation. In malignant trophoblastic disease the total lymphocyte counts, T cell counts. B-cell counts, lymphocyte responses to mitogens and serum IgA levels were significantly lower than in normal women 6 wk after pregnancy. In those who responded to chemotherapy, these indices rose to the levels of post-pregnancy controls. An 'immune profile score' based on these indices was found to be a useful prognostic index. All patients with hydatidiform mole who had a score of 7 or less developed malignant trophoblastic disease, while the two patients with malignant trophoblastic disease who died had the lowest scores of the series. PMID- 6251217 TI - Intracellular levels and stimulated release of lysosomal enzymes from human peripheral blood monocytes and monocyte-derived macrophages. PMID- 6251218 TI - Estrogen receptor based imaging agents. 2. Synthesis and receptor binding affinity of side-chain halogenated hexestrol derivatives. AB - We have synthesized as potential imaging agents for human breast tumors a series of hexestrol analogues bearing the halogens fluorine, chlorine, bromine, and iodine at the terminus of the hexane chain. The binding affinity of these compounds for the estrogen receptor from uterine tissues forms a monotonically decreasing series, starting at 129% of that of estradiol for the fluoro analogue and decreasing to 60% for the iodo analogue. Such a modest decrease in binding affinity is thought to reflect the preference of the receptor for lipophilic groups and for substituents of moderate steric size at this site, parameters which change in opposite directions in the halogen sequence going from fluorine to iodine. Three estrogenic bis(trifluoromethyl)diphenylethylenes, prepared by DuPont, also showed substantial binding affinities for the estrogen receptor. In terms of ease of radiolabeling and high receptor binding selectivity, the compound that appears to be the most promising candidate for a breast tumor imaging agent in these series is the chain terminal fluorohexestrol. PMID- 6251219 TI - Structure-activity relationship of diphenylthiourea antivirals. AB - The dependence between chemical structure and antiviral activity of N,N' diphenylthioureas is studied by synthesis and testing of model compounds and use of conformational data. The analysis revealed a number of structural features as essential for the antiviral effect: (1) the presence of an intact -NHC(==S)NH- grouping; (2) the presence of a substituent of the XH type (X = O, NH) in the aromatic ring; (3) the distance between these substituents and the sulfur atom in the 6.68-6.75 A range for the active compounds: (4) a trans conformation of the C(==S)NH-group bound to the substituted phenyl ring. The directed synthesis of compounds satisfying the above requirements yielded the derivative N-phenyl-N'-(m aminophenyl)thiourea exhibiting a very high antipicornavirus activity in vitro and several other active analogues (four out of seven synthesized). The possible mechanism of interaction between the active diphenylthiourea derivatives and the viral target is discussed. PMID- 6251220 TI - Ocular physiology. PMID- 6251221 TI - Scanning electronmicroscopy of the jejunum in enteritis necroticans. AB - Intestinal tissue resected at laparotomy from patients in Papua New Guinea at various clinical stages of enteritis necroticans, locally known as pig-bel, has been examined under the scanning electronmicroscope. Evidence obtained from parallel studies of experimental infection in pigs is presented. Progressive destruction of the intestinal mucosa was seen during the course of the disease in man. Numerous filamentous rods morphologically consistent with the appearance of Clostridium perfringens type C, were seen to be attached the affected areas of gut and were associated with the necrotic tissue. The mechanism of pathogenicity includes a stage of attachment to the surfaces of jejunal villi, local multiplication, and the production of beta toxin which may be protected from tryptic digestion by the inadequacy of pancreatic protease production in susceptible subjects and by the ingestion of a trypsin inhibitor. The association of the condition with pork feasting is discussed. PMID- 6251222 TI - Evidence of voltage-induced channel opening in Na/K ATPase of human erythrocyte membrane. AB - Previous studies have shown that human erythrocytes when subjected to a high voltage pulsation, in the microsecond time range, lysed in an isotonic medium. The hemolysis was the result of the colloid osmotic swelling, which, in turn, was caused by the voltage perforation of the red cell membranes. In this work we demonstrate that in a low ionic medium at least 35% of the pores was related to the opening of Na+/K4 ATPase channels. The membrane conductance generated by the externally applied electric field could be partially blocked by a specific inhibitor, ouabain, or by a specific cross-linkin g reagent, Cu++-phenanthroline, of the ATPase. The effect of ouabain was saturable and had a mid-point of saturation at 0.15 microM. This value agrees with the physiological inhibition constant of the drug. K+ ion in the external medium suppressed the effect of ouabain, as has also been demonstrated n physiological studies. Experiment presented in this communicaton also suggests that the Na+/K+ ATPase was not perforable in a high ionic medium, and that a large fraction of the voltage induced pores occurred at as yet unidentified sites. PMID- 6251224 TI - The role of electrogenic pump in Chara corallina. AB - The conductance, G, and the electromotive force, E, of the Chara membrane were determined accurately by using the current-clamp technique. The measurements at the final steady state of inhibitor poisoning give the conductance, g1, and the electromotive force, E1, of the passive ion conducting pathways. By knowing these values the conductance, g2, and the electromotive force, E2, of the electrogenic pump can be calculated from the measured G and E at each time during the progress of inhibitor poisoning. The local closed circuit current, i, which usually causes a hyperpolarization across the passive conducting pathways, can be calculated by using g1, g2, E1 and E2 thus determined. The values of g2 and i decrease monotonically to zero with the progress of poisoning, while E2 approaches E1 asymptotically after a transient hyperpolarization. During excitation i increases markedly. Such an increased inward current through the passive conducting pathways may help in accelerating the inactivation of the excitatory mechanism. PMID- 6251223 TI - Effect of quinidine on Na, H+, and water transport by the turtle and toad bladders. AB - The effect of quinidine on Na and H+ transport by the turtle bladder and water transport by the toad bladder was examined. Quinidine inhibited the short-circuit current and the potential difference in a dose-dependent fashion. The effect of quinidine on the short-circuit was not dependent on extracellular calcium concentration and was not reversible with removal of the drug. Quinidine inhibited H+ secretion in a dose-dependent fashion. The effect of quinidine on H+ secretion also was not dependent on extracellular calcium concentration and was not reversible, either with removal of the drug or with stimulation of H+ secretion with 5% CO2. The effect of quinidine on Na or H+ transport could not be elicited by an equivalent dose of tetracaine, suggesting that the inhibitory effect of quinidine is not dependent on its anesthetic properties. Quinidine also inhibited vasopressin and cyclic AMP stimulated water flow in the toad bladder. Quinidine did not alter calcium uptake by the turtle bladder but increased calcium efflux by the turtle and toad bladders. These observations suggest that a rise in cytosolic calcium is responsible for the inhibitory effect of quinidine on Na, H+, and water transport. PMID- 6251226 TI - Replication of ultraviolet-irradiated simian virus 40 in monkey kidney cells. PMID- 6251225 TI - Ion transport across the isolated intestinal mucosa of the winter flounder, Pseudopleuronectes americans: II. effects of cyclic AMP. AB - Addition of cyclic AMP and theophylline to the intestinal mucosa of the winter flounder, Pseudopleuronectes americanus decreased short-circuit current and net Na and Cl absorption and increased total conductance and the serosa-to-mucosa unidirectional Cl flux (JsmCl). The last two changes were independent of the original rate of NaCl absorption and persisted even when net absorption of Na and Cl had been abolished by ouabain. Voltage clamp experiments revealed that the increment in JsmCl produced by cyclic AMP is PD-insensitive and therefore not due to an increase in the Cl conductance of the paracellular shunt. Cyclic AMP appears, therefore, both to inhibit net NaCl absorption and to increase the Cl permeability and total conductance of the intestinal epithelial cells; its failure to stimulate secretion (in contrast to its action on mammalian intestine) may be related to the absence of crypts in flounder intestinal epithelium. PMID- 6251227 TI - Heterogeneity of minicircles in kinetoplast DNA of Leishmania tarentolae. PMID- 6251228 TI - Regulatory light-chains and scallop myosin. Full dissociation, reversibility and co-operative effects. PMID- 6251229 TI - A cis-dominant regulatory mutation linked to the argB-argC gene cluster in Saccharomyces cerevisiae. PMID- 6251230 TI - Cold-sensitive regulatory mutants of simian virus 40. PMID- 6251231 TI - The specific non-symmetrical sequence recognized by restriction endonuclease MboII. PMID- 6251232 TI - Cloning of human mitochondrial DNA in Escherichia coli. PMID- 6251233 TI - Properties of cardiac contractions in zero sodium solutions: intracellular free calcium controls slow channel conductance. PMID- 6251234 TI - Maintained differentiation in rat cardiac monolayer cultures: tetrodotoxin sensitivity and ultrastructure. PMID- 6251235 TI - Myeloproliferative virus, a cloned murine sarcoma virus with spleen focus-forming properties in adult mice. AB - Myeloproliferative virus, derived from Moloney sarcoma virus, causes erythroleukemia and myeloid leukemia in adult mice. This virus is also capable of fibroblast transformation in vitro. The virus consists of two separable biological entities which have been cloned. The helper virus component caused no visible changes in adult mice, whereas the defective virus induced both spleen focus formation and a large increase in erythroid precursor cells but retained the sarcoma virus property of transforming fibroblasts in vitro. Thus, myeloproliferative virus is the first murine sarcoma virus which induces erythroleukemia in adult animals. PMID- 6251236 TI - Polyoma virus DNA: Sequence from the late region that specifies the leader sequence for late mRNA and codes for VP2, VP3, and the N-terminus of VP1. AB - The DNA sequence of part of the late region of the polyoma virus genome is presented. This sequence of 1,348 nucleotide pairs encompasses the leader region for late mRNA and the coding sequence for the two minor capsid proteins VP2 and VP3. The coding sequence for the N-terminus of the major capsid protein overlaps the C-terminus of VP2/VP3 by 32 nucleotide pairs. From the DNA sequence the sizes and sequences of VP2 and VP3 could be predicted. Potential splicing signals for the processing of late mRNA's could be identified. Comparisons are made between the sequence of polyoma virus DNA and corresponding regions of simian virus 40 DNA. PMID- 6251237 TI - Polyoma virus DNA: complete nucleotide sequence of the gene which codes for polyoma virus capsid protein VP1 and overlaps the VP2/VP3 genes. AB - The nucleotide sequence of part of the late region of the polyoma virus genome was determined. It contains coding information for the major capsid protein VP1 and the C-terminal region of the minor proteins VP2 and VP3. In the sequence with the same polarity as late mRNA's, all coding frames are blocked by termination codons in a region around 48 units on the physical map. This is the region where the N-terminus of VP1 and the C-termini of VP2 and VP3 have been located (T. Hunter and W. Gibson, J. Virol. 28:240-253, 1978; S. G. Siddell and A. E. Smith, J. Virol. 27:427-431, 1978; Smith et al., Cell 9:481-487, 1976). There are two long uninterrupted coding frames in the late region of polyoma virus DNA. One lies at the 5' end of the sequence and contains potential coding sequences for VP2 and VP3. The other contains 383 consecutive sense codons starting with the ATG at nucleotide position 1,218, extends from 47.5 to 25.8 units counterclockwise on the physical map, and is located where the VP1 gene has been mapped. The VP1 gene overlaps the genes for proteins VP2/VP3 by 32 nucleotides and uses a different coding frame. From the DNA sequence, the amino acid sequence of VP1 was predicted. The proposed VP1 sequence is in good agreement with other data, namely, with the partial N-terminal amino acid sequence and the total amino acid composition. The VP1 coding frame terminates with a TAA codon at 25.8 map units. This is followed by an AATAAA sequence, which may act as a processing signal for the viral late mRNA's. When both nucleotide and amino acid sequences are compared with their counterparts in the related simian virus 40, extensive homologies are found over the entire region of the two viral genomes. Maximum homology appears to occur in those regions which code for the C-termini of the VP1 proteins. The overlap region of VP1 with VP2/VP3 of polyoma virus is shorter by 90 nucleotides than is that of simian virus 40 and shows very limited homology with the simian virus 40 sequence. This leads to the suggestion that the overlap segments of both viruses have been freed from stringency imposed on drifting during evolution and that proteins VP2 and VP3 of polyoma virus may have been truncated by the appearance of a termination codon within the sequence. PMID- 6251238 TI - Partial amino-terminal sequences of the polyoma nonhistone proteins VP1, VP2, and VP3 synthesized in vitro. AB - The three polyoma virus capsid proteins VP1, VP2, and VP3 were synthesized in vitro in the presence of several radiolabeled amino acids and, after purification on sodium dodecyl sulfate-polyacrylamide gels, were subjected to sequential Edman degradation. The partial amino-terminal amino acid sequences obtained were compared with the sequence of amino acids predicted from the polyoma virus DNA sequencing (Arrand et al., J. Virol. 33:606--618, 1980). Together, these results showed that the 5' ends of the VP1, VP2, and VP3 coding sequences are located 1,217, 289, and 634 nucleotides, respectively, from the junction of HpaII restriction fragments 3 and 5. PMID- 6251239 TI - Topography of the three late mRNA's of polyoma virus which encode the virion proteins. AB - The three cytoplasmic polyadenylated mRNA's which separately encode the three capsid proteins (VP1, VP2, and VP3) of polyoma virus were mapped on the viral genome by one- and two-dimensional gel electrophoreses of nuclease S1-resistant RNA-DNA hybrids. The mRNA's, which we designated mVP1, mVP2, and mVP3 to indicate the coding functions deduced from the cosedimentation of the RNAs and the messenger activities, comprise an overlapping set of 3'-coterminal molecules which also share a heterogeneous family of noncoding 5'-terminal regions (Flavell et al., Cell 16:357--371, 1979; Legon et al., Cell 16:373--388, 1979). The three species differ in the length of the 3' colinear coding region which is spliced to the 5' leader sequences. The common polyadenylated 3' end maps at map unit 25.3. The 5' ends of the colinear bodies of mVP1, mVP3, and mVP2 map at 48.5, 59.5, and 66.5 map units, respectively. An examination of the polyoma virus DNA sequence (Arrand et al., J. Virol. 33:606--618, 1980) in the vicinities of splicing sites approximated by the S1 gel mapping data for sequences common to the ends of known intervening sequences allowed prediction of the precise splice points in polyoma virus late mRNA's. In all three cases, the leader sequences are joined to the mRNA bodies at least 48 nucleotides before the translational initiation codon used in each particular messenger. The start signal which functions in each mRNA is the first AUG (or GUG) triplet after the splice junction. PMID- 6251240 TI - Biochemical analysis of murine leukemia viruses isolated from radiation-induced leukemias of strain BALB/c. AB - Murine leukemia viruses isolated from radiation-induced BALB/c leukemias were characterized with respect to viral proteins and RNA. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the viral structural proteins revealed that for p12, p15, p30, and gp70, three of four electrophoretic variants of each could be detected. There was no correlation found between any of these mobilities and N- or B-tropism of the viruses. Proteins of all xenotropic viral isolates were identical in their gel electrophoretic profiles. The similar phenotypes of multiple viral clones from individual leukemias and of isolates grown in different cells suggest that the polymorphism of ecotropic viruses was generated in vivo rather than during in vitro virus growth. By two-dimensional fingerprinting of RNase T1-resistant oligonucleotides from 70S viral DNA, the previously reported association of N- and B-tropism with two distinct oligonucleotides was confirmed. The presence of two other oligonucleotides was correlated with positive and negative phenotypes of the virus-coded GIX cell surface antigen. The RNAs of two B-tropic isolates with distinctive p15 and p12 phenotypes differed from the RNA of a prototype N-tropic virus by the absence of three oligonucleotides mapping in the 5' portion (gag region) of the prototype RNA. In addition, one small-plaque B-tropic virus displayed extensive changes in the RNA sequences associated with the env region of the prototype. PMID- 6251241 TI - DNA binding properties of simian virus 40 T-antigens synthesized in vivo and in vitro. AB - Simian virus 40 large T- and small t-antigens have been shown previously to share immunological determinants and common sequences and to have roles in virus induced cell transformation. However, only large T-antigen is a DNA binding protein. Under all conditions tested, small t-antigen did not interact with DNA. Large T-antigen synthesized in infected cells bound to both native calf thymus and simian virus 40 DNAs. As its binding efficiency was less than 100%, it is likely that there are different forms of T-antigen which vary in their affinity for DNA. Large T-antigen synthesized in cell-free protein-synthesizing systems primed by simian virus 40 mRNA also bound to DNA-cellulose, whereas small t antigen similarly synthesized in vitro did not. An 82,000-molecular-weight T antigen polypeptide synthesized in cell-free protein-synthesizing systems primed by simian virus 40 complementary RNA transcribed in vitro from simian virus 40 DNA by Escherichia coli RNA polymerase bound efficiently to simian virus 40 DNA. As this product did not share sequences with the small t-antigen, it can be concluded that the amino-terminal portion of the T-antigen is not required for some of its specific DNA binding properties. PMID- 6251242 TI - Distinct transformation phenotypes induced by polyoma virus and simian virus 40 in rat fibroblasts and their control by an early viral gene function. AB - Several transformed cell lines established from Fisher rat cells (FR 3T3) infected with wild-type polyoma virus or simian virus 40 or early temperature sensitive mutants (polyoma tsa and simian virus 40 tsA30) were studied for their transformation phenotypes. The distinct patterns which were obtained for polyoma and simian virus 40 transformants led to the conclusion that these two viruses express different transforming abilities in rat cells. The results obtained with temperature-sensitive mutant-derived transformants indicate that all of the transformation characteristics studied so far may be under the control of a viral function in polyoma tsa-transformed cells. PMID- 6251243 TI - Control of early gene expression of bacteriophage T4: involvement of the host rho factor and the mot gene of the bacteriophage. AB - Many early mRNA species of bacteriophage T4 are not synthesized after infection of Escherichia coli in the presence of chloramphenicol. This has been interpreted as a need for T4 protein(s) to be synthesized to allow expression of some early genes, e.g., those for deoxycytidinetriphosphatase, deoxynucleosidemonophosphate kinase and UDP-glucose-DNA beta-glucosyltransferase. In the experiments described here, early mRNA of bacteriophage T4 was allowed to accumulate during chloramphenicol treatment. After the addition of rifampin to inhibit further RNA synthesis, and subsequent removal of chloramphenicol, the accumulated mRNA was permitted to express itself into measured enzyme activities. It was shown that the early mRNA species coding for deoxycytidinetriphosphatase and UDP-glucose-DNA beta-glucosyltransferase could be formed in the presence of chloramphenicol if the E. coli host cell carried a mutation in the structural gene for the RNA chain termination factor rho. This was interpreted to mean that T4 protein(s) with anti rho activity is normally required for the expression of these two early genes. An altered rho-factor could not, however, relieve the need of phage protein synthesis for the formation of another early mRNA, that coding for deoxynucleosidemonophosphate kinase. In this case the mot gene of T4 seemed to be involved, since the primary infection of E. coli cells with the mot gene mutant tsG1 did not allow subsequent deoxynucleoside monophosphate kinase mRNA synthesis after wild-type phage infection in the presence of chloramphenicol. In control experiments, deoxynucleoside monophosphate kinase mRNA synthesis induced by wild type phage superinfecting in the presence of chloramphenicol was facilitated by the primary infection with T4 phage containing an unmutated mot gene. PMID- 6251244 TI - Bacteriophage XP-12-induced exonuclease which preferentially hydrolyzes nicked DNA. AB - An exonuclease has been partially purified from XP-12-infected Xanthomonas oryzae which is not found in uninfected X. oryzae. Although both the phage-induced exonuclease and the major host exonucleolytic DNase released 5'-mononucleotides, these enzymes differed in their chromatographic behavior, pH optimum, salt inhibition, and heat sensitivity. These two exonucleases preferred different substrates. Nicked native DNA was the best substrate for the phage-induced enzyme, whereas denatured DNA was the best substrate for the host enzyme. Also, the host enzyme had a significant preference for denatured or nicked, normal cytosine-containing DNA (e.g., X. oryzae or T7 DNA) over similarly denatured or nicked 5-methylcytosine-rich DNA (namely, XP-12DNA), whereas the phage-induced enzyme hydrolyzed both types of DNA equally well. PMID- 6251245 TI - Integration of the adeno-associated virus genome into cellular DNA in latently infected human Detroit 6 cells. AB - A clone of human cells (Detroit 6) latently infected by adeno-associated virus (AAV) has been characterized with regard to the status of the viral DNA. In both early (9 to 10) and late (118) passages of the clone, AAV-DNA was recombined with host DNA, at least in some cases as a head-to-tail tandem repeat, via the terminal sequences of the viral genome. However, it was not possible to distinguish between integration into chromosomal DNA and very large plasmids (< 20 x 10(6) molecular weight) which contain both viral and cellular DNA sequences. Although evidence for some modifications of the viral sequence was obtained, most of the integrated sequences appeared to be intact. In some cases sequences of undetermined origin separated adjacent copies of the viral genome. Free copies of the AAV genome were detectable in late passage cells, but not in early passage cells. The orientation of nucleotide sequences present in the free AAV DNA from late passage cells was indistinguishable from that of virion DNA. With the notable exception, the organization of the integrated AAV sequences as determined by restriction enzyme digestion remained constant with continued passage. Digestion with SmaI, which cleaves within the palindromic region of the terminal repetition in AAV DNA, produced reproducibly different patterns when early and late passage DNAs were compared. Several models for rescue of free copies of the genome from the integrated DNA are possible, all of which involve the terminal repetition. PMID- 6251246 TI - Isolation and translation of mRNA encoded by a specific region of the herpes simplex virus type 1 genome. AB - We have examined in detail the major mRNA species encoded by the region of the herpes simplex virus type 1 genome encoded by HindIII fragment K (0.53-0.59 from the left end of the prototype arrangement of the genome) by using this restriction fragment bound to cellulose as a reagent for isolation of this mRNA. Before viral DNA replication in infected cells (early), a major species of viral mRNA 5.2 kilobases (kb) in length is abundant. After the onset of viral DNA replication (late), four mRNA species are abundant: 7, 5.2, 3.8, and 1.8 kb in size. We have used reverse transcriptase from avian myeloblastosis virus to make DNA complementary to these RNA species and their 3' ends. We have shown by hybridization of this complementary DNA to Southern blots of herpes simplex virus type 1 DNA that the 7-, 5.2-, and 1.8-kb mRNA species have their 3' ends to the right of 0.59 and are at least partially colinear. The 3.8-kb mRNA has a 3' end mapping to the left of the 3' ends of these other species. In vitro translation of HindIII fragment K-specific mRNA in a reticulocyte lysate system yielded three major polypeptide products: 140,000, 122,000, and 54,000 daltons (d). Less prominent species of 86,000 and 65,000 d also were produced. Translation of size fractionated HindIII fragment K-specific mRNA showed that the 7-, 5.2-, and 3.8 kb mRNA's encoded the 54,000-, 140,000-, and 122,000-d polypeptides, respectively. The 140,000-d polypeptide was the major polypeptide translated using early HindIII fragment K-specific mRNA as a template. The 3.8-kb mRNA also encoded the 86,000-d polypeptide, whereas the 1.8-kb mRNA encoded a polypeptide that was indistinguishable from the 54,000-d polypeptide encoded by the 7-kb mRNA, in addition to the 65,000-d polypeptide. The implications of the data are discussed. PMID- 6251247 TI - Arrangement of integrated avian sarcoma virus DNA sequences within the cellular genomes of transformed and revertant mammalian cells. AB - We have examined the arrangement of integrated avian sarcoma virus (ASV) DNA sequences in several different avian sarcoma virus transformed mammalian cell lines, in independently isolated clones of avian sarcoma virus transformed rat liver cells, and in morphologically normal revertants of avian sarcoma virus transformed rat embryo cells. By using restriction endonuclease digestion, agarose gel electrophoresis, Southern blotting, and hybridization with labeled avian sarcoma virus complementary DNA probes, we have compared the restriction enzyme cleavage maps of integrated viral DNA and adjacent cellular DNA sequences in four different mouse and rat cell lines transformed with either Bratislava 77 or Schmidt-Ruppin strains of avian sarcoma virus. The results of these experiments indicated that the integrated viral DNA resided at a different site within the host cell genome in each transformed cell line. A similar analysis of several independently derived clones of Schmidt-Ruppin transformed rat liver cells also revealed that each clone contained a unique cellular site for the integration of proviral DNA. Examination of several morphologically normal revertants and spontaneous retransformants of Schmidt-Ruppin transformed rat embryo cells revealed that the internal arrangement and cellular integration site of viral DNA sequences was identical with that of the transformed parent cell line. The loss of the transformed phenotype in these revertant cell lines, therefore, does not appear to be the result of rearrangement or deletions either within the viral genome or in adjacent cellular DNA sequences. The data presented support a model for ASV proviral DNA integration in which recombination can occur at multiple sites within the mammalian cell genome. The integration and maintenance of at least one complete copy of the viral genome appear to be required for continuous expression of the transformed phenotype in mammalian cells. PMID- 6251248 TI - Isolation of a foot-and-mouth disease polyuridylic acid polymerase and its inhibition by antibody. AB - A template-dependent polyuridylic acid [poly(U)] polymerase has been isolated from BHK cells infected with foot-and-mouth disease virus (FMDV). Enzyme activity in a 20,000 x g supernatant of a cytoplasmic extract was concentrated by precipitation with 30 to 50% saturated ammonium sulfate. The poly(U) polymerase was freed of membranes by sodium dodecyl sulfate and 1,1,2 trichlorotrifluoroethane extraction, and RNA was removed by precipitation with 2 M LiCl. The solubilized poly(U) polymerase required polyadenylic acid as template complexed to an oligouridylic acid primer and Mg2+ for activity, but was inhibited by Mn2+. Antisera from animals infected with FMDV had previously been shown to inhibit the activity of FMDV RNA replicase complexed to the endogenous RNA template. The same antisera also inhibited the activity of poly(U) polymerase. Antisera depleted of antibody by absorption with the virus infection associated antigen of FMDV no longer inhibited replicase and polymerase activities. The evidence suggests that FMDV RNA replicase, poly(U) polymerase, and the virus infection-associated antigen share a common protein. PMID- 6251249 TI - Intervening sequence between the leader region and the nucleopcapsid gene of vesicular stomatitis virus RNA. AB - The base sequence at the 3' end of vesicular stomatitis virus RNA was determined by using terminal labels and chemical RNA sequencing. The leader RNA was complementary to 47 bases at the 3' terminus, whereas the nucleocapsid gene (N) began 51 nucleotides from the 3' end of the genomic RNA. The intervening bases were 3'...GAAA...5' for the Indiana serotype and 3'...GAAAA...5' for the New Jersey serotype. The complements of these bases did not appear in either the leader RNA or the N mRNA. This sequence may function as a stop signal or cleavage site during transcription. Furthermore, processing or termination at this sequence must be inhibited during the production of full-length RNA plus-sense strands (replication). We recently found similar sequences approximately 46 to 48 nucleotides from the 3' ends of several defective interfering particle RNAs where the short defective interfering particle transciption products terminate. This sequence is present also at the end of the polymerase (L) gene. PMID- 6251250 TI - State of hepatitis B viral DNA in a human hepatoma cell line. AB - PLC/PRF/5, a tissue culture cell line isolated from a human hepatocellular carcinoma and producing hepatitis B surface antigen, was studied for the presence of hepatitis B virus (HBV)-specific DNA and RNA. PLC/PRF/5 cell DNA accelerated the rate of reassociation of HBV [32P]DNA, and quantitative experiments indicated that the cells contained approximately four copies of viral DNA per haploid, mammalian cell DNA equivalent. PLC/PRF/5 DNA accelerated the rate of reassociation of all individual restriction endonucleases HincII and HaeIII fragments of HBV [32P]DNA, indicating that DNA from all regions of the viral genome is present in the cells. This suggests that these cells contain at least most, and possibly all, of the viral genome. Digestion of PLC/PRF/5 cell DNA with restriction endonuclease HindIII (an enzyme found not to cleave the DNA of any HBV isolate so far examined) yielded only three fragments, all larger than virion DNA, which contained HBV DNA base sequences, suggesting that HBV DNA is integrated in high-molecular-weight DNA at three different sites in these cells and that there is no viral DNA in an episomal form. PLC/PRF/5 cell [32P]RNA was found to hybridize with all restriction fragments of HBV DNA adequately tested, indicating that at least most, and possibly all, of the viral DNA in these cells is transcribed. PMID- 6251251 TI - Oligonucleotide sequence analyses indicate that vesicular stomatitis virus large defective interfering virus particle RNA is made by internal deletion: evidence for similar transcription polyadenylation signals for the synthesis of all vesicular stomatitis virus mRNA species. AB - RNase T(1) oligonucleotide fingerprint analyses of three vesicular stomatitis virus Indiana serotype small defective interfering (DI) particle RNA species indicate that they only have oligonucleotides derived from the 5' region of the viral genome. These studies also indicate that these three DI RNAs have partial L gene sequences as well as two 5' viral oligonucleotides (59 and 70) that are not transcribed into L (or other) mRNA species (J. P. Clewley and D. H. L. Bishop, J. Virol. 30:116-123, 1979). Analyses of the large DI RNA (LT DI) reveal a different origin. The LT DI RNA has oligonucleotides derived from both the 3' end of the genome (including all the large oligonucleotides identified for N, NS, M, and G genes), in addition to at least one of the 5'-proximal L gene oligonucleotides (47), as well as all seven oligonucleotides (3, 38, 42, 43, 44B, 59, and 70) that are not protected from nuclease digestion after the formation of mRNA-viral RNA duplexes (Clewley and Bishop). It appears therefore that the genesis of LT RNA involves a deletion of internal L gene sequences from the viral RNA. Oligonucleotide sequence analyses have been undertaken on several of the vesicular stomatitis viral RNA oligonucleotides, including all seven (3, 38, 42, 43, 44B, 59, and 70) that are not transcribed into mRNA. The analyses confirm that oligonucleotides 59 [3'...GAACACCAAAAAUAAAAAAUA(G)...5'] and 70 [3'...GACCAAAACACCA(G)...5'] are at the 5'-end region of the viral genome. Oligonucleotide 38 [3'...GAAAUUCAUACUUUUUU(U)(G)...5'] may represent the termination signal for L mRNA synthesis (R. A. Lazzarini, personal communication). Oligonucleotide 43 [3'...GUAUACUUUUUUU(G)...5'] corresponds to the sequence shown to be the N gene mRNA polyadenylation signal (D. J. McGeoch, Cell 17:673-681, 1979). The other three oligonucleotides share a common feature with oligonucleotides 43 and 38, viz., a stretch of 6 or 7 U residues preceded by an AUAC sequence. Thus the sequence of oligonucleotide 3 is 3'...GAAUUAAUAUAAAAUUAAAAAUUAAAAAUACUUUUUU(U)(G)...5', whereas that of oligonucleotide 42 is 3'...GAUACUUUUUUUCAU(U)(G)...5', and that of oligonucleotide 44B is 3'...G(U)AUACUUUUUU(G)...5'. These sequence analyses suggest a common polyadenylation signal for the synthesis of all vesicular stomatitis virus mRNA species, i.e., the sequence (3')...AUACUUUUUU(U)...(5'). PMID- 6251252 TI - Defective interfering particle generated by internal deletion of the vesicular stomatitis virus genome. AB - The genome structure of the long, truncated defective interfering particle derived from the heat-resistant strain of vesicular stomatitis virus has been examined. Stocks of this defective interfering particle are shown to contain several different species having information primarily from the 3' half of the vesicular stomatitis virus genome; the proportions of these components vary depending on the passage history of the stock. The two most abundant types have been identified and characterized. One has complementary 5' and 3' termini and consequently appears as a circular molecule when examined by electron microscopy. The other cannot circularize and remains linear. The circular forms are consistently 8 to 10% longer than the linear molecules. Rapid sequencing analyses reveal that both forms retain the 5' parental viral terminal sequence, but only the linear form retains the parental 3'-terminal sequence which is the complement of the 5' end. Hybridization experiments and electron microscopic analyses indicate that the linear form has retained 320 to 350 nucleotides of the 5' parental sequence and was probably generated by an internal deletion of the vesicular stomatitis virus genome. PMID- 6251253 TI - Molecular cloning of the Harvey sarcoma virus circular DNA intermediates. II. Further structural analyses. AB - Three species of unintegrated supercoiled Harvey sarcoma virus DNA (6.6, 6.0, and 5.4 kilobase pairs) have been molecularly cloned from Harvey sarcoma virus infected cells. On the basis of restriction enzyme analyses, the 6.6- and 6.0 kilobase pair viral DNAs contain two and one copies, respectively, of a 650-base pair DNA segment which contains sequences present at the 3' and 5' termini of the viral genome. R-loop structures formed between Moloney leukemia virus RNA and the cloned Harvey sarcoma virus DNA indicated that about 500 base pairs of the 650 base pair repeating segment was complementary to the 3' end of the viral RNA. During amplification in the Escherichia coli host, some recombinants containing the 6.6- or the 6.0-kilobase pair Harvey sarcoma virus DNA insert acquired or lost the complete 650-base pair DNA segment. These changes occurred in both recA+ and recA- E. coli. PMID- 6251255 TI - Transformation of rat fibroblast cells with early mutants of polyoma (tsa) and simian virus 40 (tsA30): occurrence of either A or N transformants depends on the multiplicity of infection. AB - Infection of rat fibroblasts with early mutants of polyoma virus (tsa) or simian virus 40 (tsA30) leads to the establishment of either temperature-independent A transformants or N transformants temperature-sensitive for the expression of the transformed phenotype. The choice between the A- and N-transformed states is not only dependent, as we reported previously (Rassoulzadegan et al., j. Virol., 28:421-426, 1978), on the growth conditions after infection, but is also a function of the multiplicity of infection (MOI); high MOI led to the predominant occurrence of A derivatives, and lower MOI led to that of N transformants. PMID- 6251254 TI - Localization of three major cappe 5' ends of polyoma virus late mRNA's within a single tetranucleotide sequence in the viral genome. AB - The nucleotide sequences at the 5' ends of polyoma virus late mRNA's were determined by direct RNA sequencing of decapped and 5'-(32)P-labeled RNase T1 oligoribonucleotides. Virus-specific polyadenylated cytoplasmic RNA, which was isolated from mouse cells late during productive infection, was enzymatically or chemically treated to specifically remove the cap structure (m(7)Gppp). The unblocked 5' ends of the viral mRNA's were then labeled enzymatically with (32)P, and the RNAs were digested with RNase T1 and fingerprinted. Three oligonucleotides derived from capped termini were isolated, and their sequences were determined to be pGmACAUUUUCUAUUUUAAGp, p(m)AmCAUUUUCUAUUUUAAGp, and p(m)AmUUUUCUAUUUUAAGp. These oligonucleotides comprise a staggered set with members 15, 17, and 18 nucleotides long, which share a common 3' sequence for 15 nucleotides. The sequences correspond exactly to the polyoma virus DNA sequence (Arrand et al., J. Virol. 33:606-618, 1980) from 66.79 to 66.46 map units (between 75 and 92 nucleotides preceding the ATG initiation codon for the capsid protein VP2). Previous results showed that the sequence between 13 and 64 nucleotides preceding the VP2 initiation codon corresponds to oligonucleotides reiterated in the leader sequence which is spliced onto the bodies of the three functionally distinct viral late mRNA's (Flavell et al., Cell 16:357-372, 1979; Legon et al., Cell 16:373-388, 1979). The three capped oligonucleotides we sequenced are derived from the first large predicted T1 oligonucleotide 5' to those detected in the leader sequence. The occurrence of a cap at each purine of a single tetranucleotide sequence reflects micro-heterogeneity either in transcriptional initiation or in processing cleavage involved in cap syntheses. PMID- 6251256 TI - Replication of the resident Marek's Disease virus genome in synchronized nonproducer MKT-1 cells. AB - MKT-1, a virus nonproducer lymphoblastoid cell line established from a Marek's disease tumor, was synchronized by double thymidine block to determine the sequence of events in the synthesis of cellular and latent marek's disease virus DNA. Cellular DNA synthesis was measured by incorporation of [3H]thymidine, whereas viral DNA synthesis was determined by DNA-DNA reassociation kinetics. The results of these studies indicate that the resident Marek's disease viral DNA in MKT-1 cells replicates during the early S phase of the cell cycle, before the onset of active cellular DNA synthesis. This observation is similar to that seen in the replication of resident Epstein-Barr virus DNA in synchronized Raji cells. PMID- 6251257 TI - Induction of neoplasms by subgroup E recombinants of exogenous and endogenous avian retroviruses (Rous-associated virus type 60). AB - Chickens susceptible to infection with subgroup E viruses were inoculated with four independent isolates of Rous-associated virus type 60 (RAV-60) that are subgroup e recombinants of endogenous and exogenous virus. Neoplasms developed in each inoculated group. Therefore, nontransforming viruses of subgroup E can induce lymphoid leukosis at a moderate rate compared with RAV-0, a subgroup E endogenous virus, suggesting that oncogenicity is not a viral envelope (env) related characteristic. Since the common (c) regions of the RAV-60s examined were of exogenous origin, we suggest that the c region rather than env is important for a high rate of induction of lymphoid leukosis and related neoplasms. PMID- 6251258 TI - Effect of a tsA mutation of simian virus 40 late gene expression: variations between host cell lines. AB - Infection of AGMK or CV-1 cells by the early simian virus 40 mutant tsA58 at the permissive temperature (32 degrees C) followed by a shift to the nonpermissive temperature (41 degrees C) caused a substantial decrease in the levels of late viral RNA in the cytoplasm of AGMK cells but not CV-1 cells. At the translational level, this depression of late viral RNA levels was reflected by a decrease in late viral protein synthesis. Thus, in AGMK cells, an early region gene product (presumably large T-antigen) appeared to be continuously required for efficient expression of the late viral genes. In contrast, late simian virus 40 gene expression, once it is initiated in CV-1 cells, continued efficiently regardless of the tsA mutation. The difference in expression of the late simian virus 40 genes in these tsA mutant-infected monkey kidney cell lines may reflect a difference in host cell proteins which regulate viral gene expression in conjunction with early viral proteins. PMID- 6251259 TI - Genetic studies of cell fusion induced by herpes simplex virus type 1. AB - Eight cell fusion-causing syn mutants were isolated from the KOS strain of herpes simplex virus type 1. Unlike the wild-type virus, the mutants produced plaques containing multinucleated cells, or syncytia. Fusion kinetics curves were established with a Coulter Counter assay for the mutants and wild-type virus in single infections of human embryonic lung (HEL) cells, for the mutants and wild type virus in mixed infections (dominance test), and for pairs of mutants in mixed infections (complementation test). In single infections, fusion began 4 to 6 h after infection and proceeded with an exponential decrease in the number of small single cells. At some later time that was characteristic of the mutant, there was a significant reduction in the rate of fusion for all but possibly one of the mutants. Although the wild-type virus did not produce syncytial plaques, it did induce a small amount of fusion that stopped abruptly about 2 h after it started. These data are consistent with the hypothesis that both mutants and wild type induce an active fusion inducer and that the activity of this inducer is subsequently inhibited. The extent of fusion is apparently determined by the length of the interval during which the fusion inducer is active. That fusion is actively inhibited in wild-type infections is indicated by the observation that syn mutant-infected cells fused more readily with uninfected cells than with wild type infected cells. Fusion was decreased in mixed infections with the mutants and wild-type virus, but the mutants displayed a codominant fusion phenotype. Fusion was not decreased in mixed infection with pairs of mutants, indicating that the mutants, with one possible exception, are members of the same complementation group. A linkage map was established for six of the mutants by analysis of recombination frequencies. PMID- 6251260 TI - Alterations in glycoprotein gB specified by mutants and their partial revertants in herpes simplex virus type 1 and relationship to other mutant phenotypes. AB - The tsB5 mutant of herpes simplex virus type 1 (HSV-1) strain HFEM was shown previously to be temperature sensitive for accumulation of the mature form of glycoprotein gB, for production or activity of a factor required in virus-induced cell fusion, and for production of virions with normal levels of infectivity. In addition, a previous study showed that virions produced by tsB5 at permissive temperature were more thermolabile than HFEM virions and contained altered gB that did not assume the dimeric conformation characteristic of HFEM. Results presented here demonstrate that, at permissive temperature, tsB5 differs from HFEM in another respect: plaques formed by tsB5 are syncytial on Vero cells (but not on HEp-2 cells), whereas plaques formed by HFEM are nonsyncytial on both cell types. In addition, our results indicate that tsB5 produces an oligomeric form of gB, but that it differs in electrophoretic mobility and stability from the gB dimers of HFEM. The major purpose of this study was to investigate the dependence of the various tsB5 mutant phenotypes on the temperature sensitivity of gB accumulation and on the alterations in oligomeric conformation of gB produced at permissive temperature. For this work the following HSV-1 strains related to tsB5 or HFEM were analyzed: (i) phenotypic revertants selected from tsB5 stocks for nonsyncytial plaque morphology on Vero cells or for ability to form plaques at restrictive temperature (38.5 degrees C); (ii) a plaque morphology variant of HFEM selected for its syncytial phenotype on Vero cells; (iii) temperature sensitive recombinants previously isolated from a cross between tsB5 and the non temperature-sensitive syncytial strain HSV-1(MP); and (iv) a phenotypic revertant selected from one of the recombinant stocks for its ability to form plaques at 39 degrees C. These strains were all compared with tsB5 and HFEM at three different temperatures in two different cell lines with respect to plaque formation, yield of infectious progeny, virus-induced cell fusion, and accumulation of gB. The results of our analyses on all the strains tested revealed the following correlations between mutant phenotypes and the accumulation and oligomeric conformation of gB. (i) There was a direct and quantitative relationship between the accumulation in infected cells of infectious progeny and of the mature form of gB, providing strong support for the hypothesis that this form of gB is necessary to the production of infectious virions. The oligomeric conformation of gB characteristic of HFEM is apparently not required for virion infectivity; nor was virion thermostability necessarily related to the presence of the HFEM-like oligomeric form of gB. (ii) The previously reported correlation between temperature sensitivity of gB accumulation and virus-induced cell fusion was confirmed for tsB5 and extended to other virus strains, and coordinate reversion of these traits was also demonstrated, providing support for the hypothesis that gB has a role in virus-induced cell fusion. At 37 degrees C, intermediate between permissive and restrictive temperatures, some of the mutants and partial revertants induced cell fusion despite reduced accumulations of the mature form of gB, suggesting that the amount of mature gB present did not determine the extent of fusion and that other forms of gB as well as other factors should be investigated with regard to the process of cell fusion. (iii) Some of the mutants and partial revertants could form plaques at 38.5 degrees C despite reduced accumulations of gB and infectious progeny, indicating that the cell-to-cell transmission of viral infection may be at least in part independent of these factors. PMID- 6251261 TI - Transformation-defective mutants of feline sarcoma virus which express a product of the viral src gene. AB - Mink cell cultures infected with the Snyder-Theilen strain of feline sarcoma leukemia virus were cloned from single cells under conditions favoring single virus-single cell interactions. The primary colonies included (i) typical feline sarcoma virus (FeSV)-transformed nonproducer clones, one of which segregated revertants, and (ii) FeSV-infected, phenotypically normal clones, three of which spontaneously converted to the transformed phenotype. The revertants and spontaneous transformants were compared with parental and sister clones expressing the opposite phenotype. Transformed subclones formed colonies in agar, were tumorigenic in nude mice, and failed to bind epidermal growth factor, whereas flat sister subclones were indistinguishable from uninfected mink cells in each of these assays. Sister subclones derived from the same infectious event contained FeSV proviruses integrated at the same molecular site, regardless of which phenotype was expressed. One revertant clone, however, lacked most FeSV proviral DNA sequences but retained terminal portions of the FeSV genome which persisted at the original site of proviral DNA insertion. Two flat subclones expressed viral RNA and the phosphorylated "gag-x" polyprotein (pp78gag-x) encoded by the gag and src sequences of the FeSV genome. Both of these clones were susceptible to retransformation by FeSV. Although unable to induce foci, the viruses rescued from these cells contained as much FeSV RNA as the focus-forming viruses rescued from transformed sister subclones and could be retransmitted to mink cells, again inducing FeSV gene products without signs of morphological transformation. We conclude that these FeSV genomes represent transformation defective mutants. PMID- 6251262 TI - Preferential replication of a class of host-substituted defective simian virus 40 variants at low temperature. AB - The host-substituted variant termed CVP8/1/P2 (EcoRI res) was first isolated several years ago after serial passage of simian virus 40 strain 777 on BSC-1 cells at 37 degrees C. When BSC-1 are coinfected with wild-type simian virus 40 strain 777 and variant CVP8/1/P2 (EcoRI res), the variant rapidly becomes the dominant species produced, often representing as much as 80% of the total DNA I synthesized after infection. We present evidence that the replicative advantage of the variant was increased when the infection was carried out at 33 rather than 37 degrees C. Also described are nine new and independent serial passage experiments carried out at 33 degrees C with several purified wild-type virus stocks, including strain 776, and both BSC-1 and primary African green monkey kidney cells. In each series variants related to CVPs/1/P2 (EcoRI res) were detected in the progeny viral genomes after four serial passages. Hybridization data suggest that at least some of these variant DNA I molecules contain simian virus 40 DNA sequences, monkey alpha-component DNA sequences (highly repetitive), and the infrequently reiterated monkey DNA sequences found in CVP8/1/P2 (EcoRI res), all covalently linked as in CPV8/1/P2 (EcoRI res). It appears that this type of variant emerges with some frequency during infection and is then preferentially replicated at 33 degrees C, thereby becoming readily detectable in passaged stocks. A variety of control experiments indicated that the repeated emergence of similar, if not identical, variants is unlikely to be the result of inadvertent cross-contamination or the presence of detectable amounts of the variant in the plaque-purified viral stocks. PMID- 6251263 TI - Shutoff of HeLa cell protein synthesis by encephalomyocarditis virus and poliovirus: a comparative study. AB - Previous experimental results have suggested that poliovirus and encephalomyocarditis (EMC) virus employ very different mechanisms for shutting off host protein synthesis. However, this conclusion is suspect, inasmuch as different cell types were used for the two viruses; hence the apparent mechanistic differences might be specific for cell type and not virus type. To test this possibility we compared shutoff mechanisms in poliovirus- and EMC virus infected HeLa cells. Striking differences were seen: poliovirus-induced shutoff was much more rapid and extensive than that induced by EMC virus; relative translation rates of certain host proteins were inhibited to different extents by the two viruses; initiation factors prepared from poliovirus-infected cells were specifically defective for translation of capped mRNA's in vitro, whereas those from EMC virus-infected cells were not. These results indicate that EMC virus and poliovirus employ different mechanisms for the shutoff of HeLa cell protein synthesis. This conclusion is consistent with much earlier work and indicates that many differences previously reported are specific to virus type. PMID- 6251264 TI - Control of simian virus 40 gene expression at the levels of RNA synthesis and processing: thermally induced changes in the ratio of the simian virus 40 early mRNA's and proteins. AB - Examination of the simian virus 40 early mRNA's from infected AGMK or CV-1 cells showed that the ratio of large T- to small t-antigen mRNA's increased with an increased incubation temperature. In tsA58 mutant-infected cells, an increased incubation temperature resulted in the overproduction of early RNAs'; however, the ratio of the early mRNA's was the same, at any temperature, in both wild-type and tsA58-infected cells. Thus, the thermally induced alteration in the early mRNA ratios was apparently not affected by the tsA mutation or by the overproduction of early RNA in tsA mutant-infected cells. Time course studies at various temperatures showed that, although the ratio of large T- to small t antigen mRNA's increased with temperature, at any one temperature it was consistent from early to late times of infection. Furthermore, the ratio of the early mRNA's adjusted in temperature shift experiments. Thus, the ratio of the early mRNA's appeared to be intrinsic to the thermodynamic environment of the cell. The thermally induced alterations in the early mRNA's were reflected at the protein level by parallel changes in the ratio of large T- to small t-antigens. These data suggest a level of gene expression control which may function at the stage of splicing. PMID- 6251265 TI - Characterization of a 170,000-dalton polyprotein encoded by the McDonough strain of feline sarcoma virus. AB - In this study, we demonstrated the expression of a 170,000-Mr polyprotein in each of several McDonough feline sarcoma virus (FeSV)-transformed mink cell clones and one McDonough FeSV-transformed rat clone. This polyprotein designated McDonough FeSV P170, contained feline leukemia virus (FeLV) p15, p12, and p30 immunological determinants and shared two of its five [35S]methionine-labeled tryptic peptides with FeLV Pr180gag-pol. Both of these peptides were shown to be specific to the p30 component of Pr180gag-pol. The remaining McDonough FeSV P170 methionine containing peptides were not represented within either FeLV Pr180gag-pol or Pr82env. Of interest, of the three peptides specific to the nonstructural component of McDonough FeSV P170, one was also represented in the 115,000-Mr polyproteins encoded by the Gardner and Snyder-Theilen strains of FeSV. These findings raise the possibility that the nonstructural components of polyproteins encoded by each of the three independently derived feline transforming viruses contained both common and unique regions. Moreover, if the sequences encoding these components are involved in transformation, as appears to be the case, our findings establish that the position of their insertion within the gag-pol region of the FeLV genome can vary among individual isolates. PMID- 6251266 TI - Derivation of a restriction map of bacteriophage T3 DNA and comparison with the map of bacteriophage T7 DNA. AB - The DNA of bacteriophage T3 was characterized by cleavage with seven restriction endonucleases. AvaI, XbaI, BglII, and HindIII each cut T3 DNA at 1 site, KpnI cleaved it at 2 sites, MboI cleaved it at 9 sites, and HpaI cleaved it at 17 sites. The sizes of the fragments produced by digestion with these enzymes were determined by using restriction fragments of T7 DNA as molecular weight standards. As a result of this analysis, the size of T3 DNA was estimated to be 38.74 kilobases. The fragments were ordered with respect to each other and to the genetic map to produce a restriction map of T3 DNA. The location and occurrence of the restriction sites in T3 DNA are compared with those in the DNA of the closely related bacteriophage T7. PMID- 6251267 TI - Integration of the simian virus 40 genome into cellular DNA in temperature sensitive (N) and temperature-insensitive (A) transformants of 3T3 rat and Chinese hamster lung cells. AB - We studied the pattern of integration of the simian virus 40 (SV40) genome into the cellular DNA of N-transformants (temperature sensitive) and A-transformants (temperature insensitive) derived from 3T3-Fisher rat and Chinese hamster lung cells. The SV40 DNA was covalently linked to the cellular DNA in both types of transformants. In the rat cells, most N-transformants contained SV40 sequences integrated at a single site; most A-transformants contained SV40 sequences integrated at two to five sites. In the Chinese hamster cells, no significant correlation between the number of integration sites and the phenotype of the transformant was found; one of three integration sites were observed for both the N- and A-transformants. Single copies and tandem repeats of SV40 sequences were observed in A- and N-transformants derived from rat cells. A-transformants arise neither by amplification of the SV40 genome nor by integration at a unique site. PMID- 6251268 TI - Persistence of herpes simplex virus genes in cells of neuronal origin. AB - The growth characteristics of the KOS strain of herpes simplex virus type 1 (HSV 1) in cell lines of nervous tissues origin were examined in an attempt to develop a tissue culture system mimicking the in vivo state of HSV-1 latency. We have previously reported that the B103 rat brain neuroma cell line is nonpermissive for growth of the KOS strain. In this report, we show that this nonpermissiveness is a temperature- and multiplicity-dependent phenomenon, with minimum virus yields at an elevated temperature and a low multiplicity of infection. Under these conditions, B103 cells survived infection with active wild-type or mutant HSV-1, whereas similarly treated Vero cells were killed. Six independent cultures of B103 cells surviving HSV-1 infection have been established. The surviving cells ceased production of any HSV-1 virus by 14 days postinfection and resumed growth and division at rates comparable to those of uninfected B103 cells. Survivor cells continued to express HSV-1-specific antigens, however, as detected by indirect immunofluorescence and by surface iodination followed by immunoprecipitation and polyacrylamide gel electrophoresis. The survivor cells did not express all of the surface proteins seen on productively infected B103 cells, and they were not susceptible to complement-mediated immune cytolysis with anti-HSV-1 antiserum. These results demonstrate that at least a portion of the HSV-1 genome is being harbored in these survivor cells. PMID- 6251269 TI - Characterization of virus produced by a lymphoma induced by inoculation of AKR MCF-247 virus. AB - We report the characterization of the virus produced by a lymphoid cell line derived from a lymphoma of an AKR mouse after injection of the polytropic AKR virus MCF-247. The virus displays polytropic host range properties and is indistinguishable from MCF-247 as judged by analysis of the large RNase T1 resistant oligonucleotides of the RNA genome. Restriction enzyme analysis of cellular DNA revealed the presence of sequences homologous to MCF-247 genomic RNA. The EcoRI cleavage fragments were characteristic of MCF-247 DNA provirus cleavage products. PMID- 6251270 TI - Middle T antigen as primary inducer of full expression of the phenotype of transformation by polyoma virus. AB - A large number of polyoma virus-transformed cells of rat, mouse, and hamster origin were examined for presence of T-antigen species. The results showed that all lines of cells contained middle and small T antigens, but not all contained a full-sized large T antigen, in some cell lines large T antigen was absent, whereas in others it was present as truncated forms lacking various lengths of the carboxy-terminal part of the protein. Cells transformed by the new viable deletion mutants of polyoma virus, dl-8 and dl-23, formed larger and smaller colonies or foci, respectively, when they were suspended in semisolid medium or plated as monolayers together with untransformed cells on a plastic surface. The deletions in the DNA of these mutants resulted in the shortening of the large and middle T antigens simultaneously without affecting the size of the small T antigen. Variation of large T-related proteins in dl-8 and dl-23-transformed cells seemed to be the same as that observed in wild-type-transformed cells. Regardless of the amount and size of large T-related protein in mutant transformed cells, the phenotype of the cells was entirely dependent on the mutant used. The results suggest that (i) persistence of large T antigen is not universally required for the maintenance of the transformation phenotype, (ii) small T antigen alone may not be sufficient for inducing the full expression of the transformation phenotype, and (iii) middle T antigen is implicated as being primarily responsible for the full expression of the phenotype of transformation. The results also provide the evidence that the carboxy-terminal region of middle T antigen and a part of large T antigen are encoded in the genome in the same DNA segment around map units 88 to 94 in different reading frames. PMID- 6251271 TI - Temperature dependency for maintenance of transformation in mouse cells transformed by simian virus 40 tsA mutants. AB - Mouse embryo fibroblasts and 3T3 cells were transformed by wild-type, tsB4, tsA7, tsA58, and tsA209 simian virus 40. Clones of transformants were generated both in soft agar and in liquid medium by focus formation and at both high and relatively low multiplicities of infection. All transformants were assayed for three phenotypes of transformation: (i) the ability to form highly multinucleated cells in cytochalasin B-supplemented medium, i.e., uncontrolled nuclear division; (ii) the capacity to continue DNA synthesis at increasing cell density; and (iii) the ability to form colonies in soft agar. The great majority of mouse embryo fibroblast transformants generated with tsA mutant virus were temperature sensitive for transformation in all three assays, regardless of the input multiplicity or whether they were generated in liquid medium or soft agar. These transformants exhibited a normal or near-normal phenotype at the nonpermissive temperature of 40 degrees C. All but one of the transformants which appeared transformed at both temperatures were in the A209 group. In contrast to mouse embryo fibroblasts, transformants generated with 3T3 cells and tsA virus were often not temperature sensitive, exhibiting the transformation phenotypes at both temperatures. This phenomenon was more often observed when 3T3 transformants were generated in soft agar. These results, along with other published data, suggest that uncontrolled nuclear division and uncontrolled DNA synthesis are a function of the simian virus 40 A gene. Finally, with the 3T3 transformants, there was often discordance in the expression of transformation among the three phenotypes. Some tsA transformants were temperature sensitive in one of two assays but were transformed at both 33 and 40 degrees C in the remaining assay(s). Other transformants exhibited a normal cytochalasin B response at either temperature but were temperature sensitive in the other assays. PMID- 6251272 TI - Replication of Chinese hamster embryo cells transformed by temperature-sensitive T-antigen mutants of simian virus 40. AB - Chinese hamster embryo cells transformed by simian virus 40 temperature-sensitive T-antigen mutants replicated when confluent at 40.5 degrees C, regardless of the selection method, selection temperature, or virus strain used. PMID- 6251273 TI - Phenotype of polyoma-induced hamster tumor cells lines. AB - Cell lines from polyoma-induced hamster tumors exhibit a fully transformed phenotype despite the absence of the 105K (105,000-dalton) form of polyoma T antigen. PMID- 6251274 TI - Three independent isolates of feline sarcoma virus code for three distinct gag-x polyproteins. AB - Cells nonproductively transformed by the Snyder-Theilen, Gardner-Arnstein, and McDonough strains of feline sarcoma virus synthesize gag-x polyproteins of 78,000, 100,000, and 180,000 daltons, respectively. These feline sarcoma virus coded products were precipitated by antisera to polypeptides encoded by the gag gene of feline leukemia virus and by rat antisera raised to feline sarcoma virus transformed rat tumor cells. Precipitation with rat antisera absorbed with feline leukemia virus showed that the x-portions of the three gag-x proteins were each antigenically distinct, suggesting that the src genes of the three independent isolates are not identical. Anti-x sera did not precipitate products from radiolabeled cat lymphoid tumor cells (FL74) and therefore lacked reactivity to the feline leukemia virus-induced tumor-specific antigen, FOCMA. PMID- 6251275 TI - Transformation of primary hamster brain cells with JC virus and its DNA. AB - We transformed primary hamster brain cells with four isolates of JC virus and JC virus DNA. Several properties of these transformants were characterized and compared to those of simian virus 40 transformants isolated under identical conditions. PMID- 6251276 TI - Frequent isolation of ecotropic murine leukemia virus after x-ray irradiation of C57BL/6 mice and establishment of producer lymphoid cell lines from radiation induced lymphomas. AB - Fractionated whole-body X irradiation of C57BL/Ka mice leads to the development of thymic leukemia in 90% of the treated animals at an average age of 6 months. Using a sensitive high-density cocultivation procedure, we were able to demonstrate the presence of ecotropic murine leukemia virus (MuLV) from 1 month post-irradiation up to leukemia development. These viruses are not specific to any one particular organ, but can be found in at least two of the three lymphoreticular tissues studied, namely, spleen, thymus, and bone marrow. Host range studies on the isolated viruses showed that both N- and B-tropic MuLV could be isolated early after irradiation. However, as mice reached an age where leukemias develop, only the B-tropic MuLV could be recovered. We have established cell lines from primary radiation-induced tumors that are being maintained in continuous culture: except one cell line, all are virus producers. The results clearly indicate that X irradiation induces ecotropic MuLV in C57BL/Ka mice and suggest that B-tropic MuLV might be involved in the disease process. PMID- 6251277 TI - Evidence for the common origin of viral and cellular sequences involved in sarcomagenic transformation. AB - The src genes of six different strains of avian sarcoma virus (ASV) were compared with those of a series of newly isolated sarcoma viruses, termed "recovery avian sarcoma viruses" (rASV's). The rASV's were isolated recently from chicken and quail tumors induced by transformation-defective (td) deletion mutants of Schmidt Ruppin Rous sarcoma virus. The RNase T1-resistant oligonucleotide maps were constructed for the RNA genomes of different strains of ASV and td mutants. The src-specific sequences, characterized by RNase T1-resistant oligonucleotides ranging from 9 to 19 nucleotides long, were defined as those mapping between approximately 600 and 2,800 nucleotides from the 3' polyadenylate end of individual sarcoma viral RNAs, and missing in the corresponding td viral RNAs. Our results revealed that 12 src-specific oligonucleotides were highly conserved among several strains of ASV, including the rASV's, whereas certain strains of ASV were found to contain one to three characteristic src-specific oligonucleotides. We previously presented evidence supporting the idea that most of the src-specific sequences present in rASV RNAs are derived from cellular genetic information. Our present data indicate that the src genes of rASV's are closely related to other known ASVs. We conclude that the src genes of different strains of ASV and the cellular sarc sequences are of common origin, although some divergence has occurred among different viral src genes and related cellular sequences. PMID- 6251278 TI - Adenovirus helper function for growth of adeno-associated virus: effect of temperature-sensitive mutations in adenovirus early gene region 2. AB - Adeno-associated virus (AAV) grows efficiently only in cells that are also infected with an adenovirus (Ad). We employed Ad mutants to determine which genes may be required for the AAV helper function. Two mutants of Ad type 5 (Ad5), Ad5ts125 and Ad5ts107, with temperature-sensitive lesions in the E72 DNA-binding protein coded by the Ad early region 2, were deficient for AAV helper functions at the nonpermissive temperature (40 degrees C). In contrast, Ad5ts149, with a temperature-sensitive lesion in the Ad early region 5, was an efficient helper of AAV at the nonpermissive temperature. In KB cells, with the Ad5ts125 or Ad5ts107 mutant as the helper, the accumulation of AAV capsid proteins and AAV particles was decreased by about two logs, whereas AAV DNA synthesis was decreased only severalfold. Cytoplasmic, polyadenylic acid-containing AAV RNA is composed of a set of overlapping, spliced RNAs having different 5' start points. With the ts125 helper at 40 degrees C there was a decreased accumulation of some but not all of these AAV RNAs. The Ad5 E72 protein may have an effect on transcription or more likely posttranscriptional processing of AAV RNA. These observations suggest additional pleiotropic effects of the multifunctional E72 protein and suggest further similarities in the actions of E72 and the simian virus 40 T-antigen. PMID- 6251279 TI - Functional organization of the Harvey murine sarcoma virus genome. AB - The comparative infectivity of Harvey murine sarcoma virus (Ha-MuSV) DNA for NIH 3T3 cells was determined for supercoiled Ha-MuSV DNA molecularly cloned in lambda phage and pBR322 at its unique EcoRI site (which is located near the middle of the 6-kilobase pair [kbp] unintegrated linear viral DNA) and for two cloned subgenomic fragments: one was 3.8 kbp and lacked about 1 kbp from each side of the EcoRI site, and the second did not contain the 3 kbp of the unintegrated linear viral DNA located on the 3' side of the EcoRI site. Each subgenomic DNA induced foci of transformed cells, but with a lower relative efficiency then genomic DNA. Transfection with intact vector Ha-MuSV DNA yielded results similar to those obtained after separation of Ha-MuSV DNA from vector DNA. Cells lines were then derived from individual foci transformed with each type of viral DNA. Focus-forming virus was recovered from transformed cells after superinfection with a helper-independent virus, but the efficiency varied by several orders of magnitude. For several transformed lines, the efficiency of recovery of focus forming virus was correlated with the structure of the Ha-MuSV DNA in the cells before superinfection. When 32P-labeled Ha-MuSV DNA probes specific for sequences on either the 3' or 5' side of the EcoRI site were used to analyze the viral RNA in the transformed cell lines, all lines were found to hybridize with the 5' probe, but some lines did not hybridize with the 3' probe. The transformed lines contained high levels of the Ha-MuSV-coded p21 or its associated GDP-binding activity. We conclude that the transforming region and the sequences that code for the viral p21 protein are both located within the 2 kilobases closest to the 5' end of the Ha-MuSV genome. PMID- 6251281 TI - Adult Wilms tumor: a report of prolonged survival and review of literature. PMID- 6251280 TI - Increased rate of RNA synthesis: early reaction of primary mouse kidney cells to infection with polyoma virus of simian virus 40. AB - The rate of transcription in isolated nuclei of primary mouse kidney cells increases by a factor of about 1.5 between 5 and 8 h after infection with polyoma virus or simian virus 40. This process requires intact virus and is inhibited by cycloheximide and actinomycin D. It appears to involve the activity of all three nuclear RNA polymerases, and evidence was obtained for an increase in the rate of synthesis of most, if not all, species of RNA that were already produced in resting cells before infection. The additional synthesis of a few new RNA species not made in uninfected cells, however, cannot be excluded. The increase in the rate of transcription seems to precede an increase in the rate of translation in infected cells. Our additional finding that large and small tumor antigens (T antigens) are synthesized at the same time after infection suggests that these cellular reactions are early consequences of the action of one or both of these T antigens in the infected cell. Experiments with simian virus 40 mutants provided strong evidence for an involvement of large-T-antigen but not of small t-antigen. These studies furthermore indicate that the increase in the transcription rate is a prerequisite for the induction of DNA replication in simian virus 40-infected mouse kidney cells. PMID- 6251282 TI - Wilms tumor extending into the dilated renal pelvis as a mold. AB - A case of Wilms tumor associated with hydronephrosis is reported. The tumor extended into the dilated renal pelvis but there was no invasion in the mucosa of the ureter or renal pelvis. PMID- 6251283 TI - Fibrosing adenocarcinoma of the intestine of a gopher snake (Pituophis melanoleucus). AB - Histologic examination of a mass from the intestine of a gopher snake revealed a neoplastic process with an excessively exuberant fibrous component. PMID- 6251284 TI - The response of some African wildlife species to foot-and-mouth disease vaccination. AB - The preservation of wildlife is of increasing importance in may countries in Africa but, due to hazards of possible transmission of disease from wild to domesticated species, the interests of the conservationist can conflict with those of the livestock owner. Foremost among transmissible diseases common to many species of both wild and domesticated animals is foot-and-mouth disease (FMD). The effects of FMD vaccination on three important wildlife species, African buffalo (Syncerus caffer), eland (Taurotragus oryx) and impala (Aepyceros melampus), are described. The pattern of response in all three species was similar to that of cattle but of a lower order. The implications are discussed and a vaccination protocol is suggested. PMID- 6251285 TI - Herpesvirus-like infection in a painted turtle (Chrysemys picta). AB - A painted turtle (Chrysemys picta) which died in captivity had marked necrosis in the liver and lungs with numerous intranuclear inclusion bodies in hepatocytes and respiratory epithelial cells. Electron microscopy revealed herpesvirus-like particles in cells in affected tissues. PMID- 6251286 TI - Clostridium perfringens wound infection associated with elastic bandages. AB - Clostridium perfringens wound infections were associated with the use of nonsterile elastic outer bandages in diabetic patients who had undergone lower extremity amputation for vascular insufficiency. In each case a second surgical procedure was required. Elastic bandages similar to those used in these procedures were found to contain C perfringens and other clostridial species. This report illustrates the need for maintenance of a sterile, nonpermeable inner barrier to prevent transudation of bacteria into the wound and the potential benefit of using sterile elastic outer bandages after amputation for vascular insufficiency. PMID- 6251287 TI - Mixed multiple endocrine neoplasia syndromes. PMID- 6251288 TI - Ethinyl estradiol and conjugated estrogens as postcoital contraceptives. AB - Five study centers enrolled 1,311 women seeking postcoital contraception methods. Ethinyl estradiol was administered at 5 mg/day and conjugated estrogens at 30 mg/day for five consecutive days starting within 72 hours of unprotected coitus. Eleven pregnancies occurred in the 976 women who had a single unprotected coitus at midcycle. Based on published information, 69 pregnancies would have been expected if no contraceptives were used. Although both treatments were effective in preventing pregnancy, ethinyl estradiol seemed to be more effective. At the two centers alternately prescribing both drugs, none of 137 women treated with ethinyl estradiol became pregnant, while six of the 132 given conjugated estrogens became pregnant. Women whose treatment commenced on the first postcoital day seemed to have lower pregnancy rates than those whose medication was delayed to the second or third postcoital day regardless of which drug was used. Side effects were mainly limited to nausea that occurred in 70% and vomiting that was experienced by 33% of all women treated. PMID- 6251289 TI - Work-related asthma comes out of hiding. PMID- 6251290 TI - Home parenteral nutrition. PMID- 6251291 TI - The tophus in calcium pyrophosphate deposition disease. AB - A 61-year-old man had a tophus on the third finger of his right hand. There was no history of arthritis, no laboratory abnormality, and no chondrocalcinosis. Crystalline material from the tophus was identified as calcium pyrophosphate dihydrate by x-ray diffraction. PMID- 6251292 TI - Prostaglandins and cyclic nucleotides: effects of PGI2 and PGE1 on cardiac hemodynamic and coronary arterial and myocardial cyclic nucleotide levels in dogs. AB - The effects of prostacyclin (PGI2) were compared with those of prostaglandin E1 (PGE1) on the cardiac hemodynamics (coronary blood flow, systemic blood pressure, cardiac output and max dp/dt of the left ventricle) in closed-chest dogs. Moreover, the effects of PGI2 were compared with those of PGE1 on the concentrations of the coronary arterial and myocardial cyclic adenosine 3':5' monophosphate (cyclic AMP) and cyclic guanosin 3':5'-monophosphate (cyclic GMP) in open-chest dogs. The intraventricular and intravenous injection of 0.1 to 4.0 microgram/kg of POGI2 increased the coronary blood flow and decreased the mean systemic blood pressure. Comparison of dose response curves for PGI2 and PGE1 in relation to the coronary blood flow indicated that PGI2 and 4 times as potent as PGE1. On the other hand, the effect of PGI2 on the systemic blood pressure was twice as potent as PGE1. The concentration of the coronary arterial cyclic AMP was significantly increased by the administration of PGI2 and PGE1 (control group: PGI2 group was 0.201 +/- 0.022 vs. 0.264 +/- 0.017 pmoles/mg tissue, p < 0.05; control: PGE1 was 0.201 +/- 0.022 vs. 0.286 +/- 0.027 pmoles/mg tissue, p < 0.05). The concentrations of the coronary arterial cyclic GMP were not significantly changed by the administration of PGI2 and PGE1, nor were those of myocardial cyclic AMP and cyclic GMP. The changes in cyclic nucleotide levels and cardiac hemodynamics induced by PGI2 were qualitatively similar to those induced by PGE1, but the change caused by PGI2 was greater than PGE1 in the coronary and systemic hemodynamics. PMID- 6251293 TI - [Shock and microcirculation, including the question of alpha, beta receptors in microcirculation]. PMID- 6251294 TI - [Metabolic approach in the management of shock: GIK therapy and DBcAMP]. PMID- 6251295 TI - [Viral etiology of idiopathic cardiomyopathies]. PMID- 6251296 TI - [Trends in cancer therapy with new particle radiotherapy. Use of pi-mesons and heavy ion beam, with special reference to our own cases]. PMID- 6251297 TI - [Re-examination of the spectrophotometric assay for serum angiotensin-converting enzyme (author's transl)]. PMID- 6251298 TI - [Closure of the wound with polyglycolic acid sutures in cardiac and thoracic surgery (author's tranls)]. PMID- 6251299 TI - [Thymus related tumor--classification and therapy (author's transl)]. PMID- 6251300 TI - [Renal parenchymal tumor induced by dimethylnitrosamine in newborn rats (author's transl)]. PMID- 6251301 TI - Isolation of antigenic mutants of type 1 poliovirus: growing the virus in the presence of homologous antiserum. PMID- 6251302 TI - Serum sialyltransferase and 5'-nucleotidase as reliable biomarkers in women with breast cancer. AB - Sialyltransferase and 5'-nucleotidase were measured in the sera of 135 women with breast cancer: 53 undergoing mastectomy for primary cancer and 83 receiving different modalities of palliative therapy for metastatic disease. The objective of this study was to determine whether these enzyme levels were associated with the extent of the disease and whether changes in these enzyme levels could be correlated with success or failure of treatment. Mastectomy caused a rapid fall of elevated enzyme levels to within the normal range in all patients with stage I breast cancer but not in those with stage II or III disease. In women with metastatic disease, elevated enzyme levels fell only in patients responding to treatment. Thus serum sialyltransferase and 5'-nucleotidase activities are reliable biomarkers of breast cancer activity, and serial measurement of these enzyme activities provides a useful tool for the monitoring of disease activity and success or failure of the treatment. PMID- 6251303 TI - Host cell-modified T-antigen in membranes of simian virus 40-transformed hamster cells. AB - Highly purified plasma membranes of simian virus 40 (SV40)-transformed hamster and mouse cells were subjected to indirect immunoprecipitation and bidimensional isoelectric focusing-immunoelectrophoresis with high-titer (greater than or equal to 512) sera against SV40 T-antigen. An SV40-specific protein of approximately 100,000 daltons and pH-4.7 isoelectric point cross-reacted immunologically with T antigen, which indicated the presence of a T-antigen species. However, this protein appeared to be host cell modified because of its low isoelectric point and its reactivity with heterologous antisera containing antibodies specific for neuraminidase- and trypsin-sensitive carbohydrate and/or peptide moieties lacking nuclear T-antigen. Another protein specific for the membranes of SV40-transformed cells had a molecular mass near 60,000 daltons and an isoelectric point at pH 4.5 and appeared closely associated with membrane T-antigen. It coprecipitated with membrane T-antigen upon direct immunoprecipitation with anti-T serum. However, when this protein was dissociated from membrane T-antigen by isoelectric focusing in the presence of Triton X-100 and urea, its reactivity with anti-T serum was lost. This suggested that the protein was not encoded in the SV40 genome. PMID- 6251304 TI - Transplacental teratogenic and carcinogenic effects in rabbits chronically treated with N-ethyl-N-nitrosourea. AB - Pregnant rabbits of two partially inbred strains, WH/J and IIIVO/J, were given ten consecutive daily ip injections of 10 mg N-ethyl-N-nitrosourea (ENU)/kg dissolved in trioctanoin starting on either day 10, 15, or 18 of gestation. Of 7 WH/J progeny weaned, 3 developed primary renal tumors at 6.8 +/- 0.6 months of age (mean +/- SE). Similarly, of 12 IIIVO/J progeny weaned, 10 developed primary renal tumors at 6.3 +/- 0.6 months of age (mean +/- SE); in addition, 1 fibroblastic osteosarcoma and 5 neurofibromas, some associated with neurilemma cysts, were observed. Renal tumors were nephroblastomas , which appeared to develop within small renal cortical cysts. The frequency of tumor induction for each strain was similar to that in our previous experiments with acute administration of ENU and ethyl-urea plus NaNO2, but the latency period (6.4 +/- 0.5 mo) was almost doubled. In addition, chronic treatment of ENU induced teratogenic effects. In a number of these progeny, a disproportionate stunting or miniaturization was evident, the frequency of which increased with the age of the treated fetuses. In contrast, holes were found in the parietal bones at birth, but with a frequency that decreased with increasing fetal age at time of treatment. No teratogenic effects were observed in the controls. PMID- 6251305 TI - [A study on pulmonary lesions in mice induced by allogeneic soluble lung antigen (author's transl)]. PMID- 6251306 TI - [Formation of ectopic excitation in the heart under the action of aconitine. II. The generation of oscillatory fluctuations of the membrane potential and current]. AB - The method of potential fixation was used to study the mechanism of the origin of membrane potential oscillations induced by aconitine (50, 100 mg/l) on isolated trabeculae of Rana ridibunda atrium. Some of the sodium channels change their properties under the effect of aconitine: these channels are activated at potentials close to the rest potential, while the rate of their inactivation is slowed down. The direct cause of the aconitine ectopic excitation are oscillations of the sodium current caused by modified channels. As a result of oscillations of the current, the membrane potential reaches the level of a regenerated response from time to time, after which generation of the excitation occurs. PMID- 6251307 TI - beta 1-Adrenergic receptors in kidney tubular cell membrane in the rat. AB - We used a beta-adrenergic antagonist, (-) 3H-dihydroalprenolol, to demonstrate binding sites in purified rat kidney preparations that consistsed of plasma membranes of cells from tubules. The tubular origin of these plasma membranes was shown by electron microscopy and Na-K-ATPase enrichment. The binding was rapid (t1/2, 78 sec) and rapidly reversible (t1/2, 48 sec). The binding sites were saturable and bound 69.8 +/- (SD) 29.1 fmoles/mg of membrane protein. The binding was stereospecific with the isomers of beta-adrenergic agonists and beta adrenergic antagonist propranolol, the (-) isomers being about 40 times more potent than the (+) isomers incompeting for these sites. (-) 3H-dihydroalprenolol had a high affinity for the binding sites, expressed by the mean equilibrium dissociation constant (KD) (KD, 7.1 nM). The beta-adrenergic antagonist (-) propranolol also showed high affinity (KD, 62.8 nM). The order of potency for inhibition of binding by beta-adrenergic agonists was: (-) isoproterenol (KD, 0.66 microM) greater than (-) epinephrine (KD, 4.3 microM) greater than or equal to (-) norepinephrine (KD, 13.5 microM). Conclusion. The (-) 3H-dihydroalprenolol binding sites in the rat kidney tubular cell membrane are beta-adrenergic receptor of the beta1 subgroup. PMID- 6251308 TI - [Current problems in the clinical immunology of infectious diseases]. PMID- 6251309 TI - Effect of dietary fiber on intestinal mucosal sodium-potassium-activated ATPase. PMID- 6251310 TI - In vitro studies of serotonin release from rat enterochromaffin cells: studies of gut serotonin release. PMID- 6251311 TI - Sertoli cell chromatin acceptor sites for androgen-receptor complexes. PMID- 6251312 TI - Assay of ethynyloestradiol in human serum and its binding to plasma proteins. PMID- 6251313 TI - Proton turnover at mitochondrial coupling sites. PMID- 6251314 TI - Theoretical analyses of the functioning of the high- and low-Km cyclic nucleotide phosphodiesterases in the regulation of the concentration of adenosine 3',5' cyclic monophosphate in animal cells. PMID- 6251315 TI - Biological activity of the tetrahydrocannabinols. PMID- 6251316 TI - Prospective study of 445 lung carcinomas with mediastinal lymph node metastases. PMID- 6251317 TI - Adenosine 3':5' cyclic monophosphate and myeloid leukemic cell proliferation in vitro. PMID- 6251318 TI - The recovery of a random variable from a noisy record with application to the study of fluctuations in synaptic potentials. AB - Analysis of fluctuations in the amplitude of evoked synaptic potentials can be severely handicapped by the presence of spontaneous synaptic potentials and recording noise. A numerical procedure has been described whereby it is possible to remove some of the masking effects of this noise from the underlying distribution of the fluctuating synaptic potentials. it is not necessary to make an initial assumption about the type of distribution which will best describe the fluctuations. To use this technique, it is necessary to measure the histograms which approximate the probability densities of both the noise, and the noisy evoked potential. It is also necessary to assume that the statistical mechanisms generating the noise are independent of those mechanisms which cause the fluctuation in synaptic transmission, and that the noise and the evoked potentials add linearly. The statistical reliability of the technique depends upon the amount of noise present, and the sample size. Problems of resolution which arise from finite sampling and high noise levels are discussed. PMID- 6251319 TI - A simple and rapid method for the assay of cyclic GMP-dependent protein kinase. AB - A method for the isolation in partially purified cyclic GMP-dependent protein kinase (cGPK) from cerebellum is described. It involves a step-elution of an ion exchange column charged with the post-mitochondrial supernatant of cerebellar homogenate. The cGPK activity is defined as the protein kinase activity in presence minus that in absence of cyclic GMP. Under the assay conditions used no interference by cyclic AMP-dependent protein kinase, and only negligible activities of cyclic nucleotide phosphodiesterase and phosphoprotein phosphatase could be detected. PMID- 6251320 TI - Attempted curative resection of ductal carcinoma of the pancreas: review of Mayo Clinic experience, 1951-1975. PMID- 6251321 TI - Biliary bypass for ductal adenocarcinoma of the pancreas: Mayo Clinic experience, 1970-1975. AB - During a recent 6-year period at the Mayo Clinic, 151 biliary bypass procedures for ductal adenocarcinoma of the pancreas were done, with operative mortality of 6.0% and an acceptable operative morbidity. Relief of jaundice was universal among survivors. Median survival was 6.0 months, and 3-year survival was 2%. These figures are compared with those for resective procedures. PMID- 6251322 TI - Antidepressant drug action and presynaptic alpha-receptors. AB - Receptors have been demonstrated on the terminations of the sympathetic adrenergic nerves. One type, the so-called alpha 2-receptors, are activated by the norepinephrine that is released from the nerve terminals into the synaptic cleft; this activation causes a reduction in the output of the transmitter (negative feedback). Recent studies have demonstrated that certain antidepressant drugs can block these alpha 2-receptors and thus prevent their inhibitory action on the release of norepinephrine. If this occurs in the brain, the increases in norepinephrine levels could help explain the antidepressant action of these agents. PMID- 6251323 TI - Ductal adenocarcinoma of the pancreas. PMID- 6251324 TI - [Absence of increase of cyclic adenosine monophosphate (cAMP) in the cerebrospinal fluid of febrile patients (author's transl)]. AB - Recent studies point toward the importance of cyclic adenosine 3',5' monophosphate (cAMP) in the genesis of fever. Experimental fever induction in animals using bacterial pyrogens is accompanied with an increase of nucleotid concentration in the cerebrospinal fluid up to duplicate normal basal values. This aspect, however, has not been studied in human pathology. The concentration of cAMP in the cerebrospinal fluid of 11 patients with fever higher than 38.5 degrees C was studied. there were no significant differences between values found in these patients (14.03 +/- 5.82 pM/ml) and those corresponding to normality (15.44 +/- 3.36 pM/ml). We think that these results did not refute the role of cAMP in the pathogenesis of fever; they are only laboratory findings in discordance to experimental results. PMID- 6251325 TI - [Histological and cytological criteria for classification of primary liver cell carcinoma (author's transl)]. AB - 23 cases of liver cell carcinoma were reclassified according to the WHO classification schema. Appropriate cases could be classified without any difficulty into the trabecular, compact and acinar type groups; there was more difficulty to classify the scirrhous type of carcinoma. Carcinoma composed by clear cells, and inacrocellular eosinophilic carcinoma with lamellar fibrosis have a lower incidence of mitoses than the other carcinoma types. AFP could be demonstrated in tumor tissue by immune histochemistry in one case only; HBs-Ag could never been shown by the aldehyd-thionin method. The ratio mitoses/apoptoses was approx. 2:1. PMID- 6251326 TI - [Diagnosis of congenital deficiency of alpha 1-antitrypsin by the immune peroxidase technique (author's transl)]. AB - 10 cases of congenital deficiency of alpha 1-antitrypsin with liver involvement were identified on clinical grounds; 10 cases of liver cirrhosis were selected by way of the diastase-PAS-reaction. In these 20 cases alpha 1-antitrypsin was demonstrated in paraffin sections by a modification of the indirect peroxidase antiperoxidase method. In all these cases the immunoreactive inclusions could be demonstrated in the hepatocytes, even when the paraffin sections were several years old. 399 cases of cirrhosis of the liver were investigated in this retrospective study; only 10 of these cases had, as mentioned above, inclusions in the hepatocytes, which were immunoreactive, PAS-positive, and resistant against diastase. PMID- 6251327 TI - Neurotransmitter receptors-biochemistry and alterations in nueropsychiatric disorders. PMID- 6251328 TI - Rapid and direct stimulation of hepatic gluconeogenesis by L-triiodothyronine (T3) in the isolated-perfused rat liver. PMID- 6251329 TI - Low permeation of systemically administered human beta-endorphin into rabbit brain measured by radioimmunoassays differentiating human and rabbit beta endorphin. PMID- 6251330 TI - Solubilization of the opiate receptor. PMID- 6251331 TI - Circadian rhythms in rat brain alpha- and beta-adrenergic receptors are modified by chronic imipramine. PMID- 6251332 TI - Independent expression of cyclic AMP dependent protein kinases related to cyclic nucleotide systems, during triiodothyronine induced cardiac hypertrophy. PMID- 6251333 TI - Effect of age on adrenergic and dopaminergic receptor binding in rat brain. PMID- 6251335 TI - [Segmental hemangiomatosis of the distal colon in a patient with Klippel Trenaunay syndrome]. PMID- 6251336 TI - [Should one operate on the small cell bronchial carcinoma?]. PMID- 6251334 TI - Glucagon and N6,O2'-dibutyryl adenosine 3':5'-monophosphate inhibition of lipogenesis and phosphofructokinase activity of hepatocytes from meal-fed rats. AB - Glucagon and N6,O2'-dibutyryl adenosine 3':5'-monophosphate (dibutyryl cyclic AMP) inhibit net glucose utilization, lactate plus pyruvate accumulation and fatty acid synthesis by isolated hepatocytes prepared from meal-fed rats. A crossover in the metabolite profile of the glycolytic intermediates occurs between fructose-6-phosphate and fructose-1,6-bisphosphate, suggesting either inhibition of phosphofructokinase or activation of fructose diphosphatase, or both. Direct assay of the enzymes in cell-free extracts of the hepatocytes indicates that dibutyryl cyclic AMP inhibits phosphofructokinase but has no effect upon fructose diphosphatase. The assay for phosphofructokinase was modified by the use of ITP in place of ATP for the phosphate donor as the ATP linked assay is complicated by an apparent time-dependent activation of the enzyme. These findings strongly suggest that cyclic AMP inhibition of phosphofructokinase explains in part cyclic AMP inhibition of aerobic glycolysis and lipogenesis by rat liver hepatocytes. PMID- 6251337 TI - [Antigenic capacity of Junin virus inactivated by photodynamic oxidation]. PMID- 6251338 TI - Calcium and O2-dependent control of inner medullary cGMP: possible role for Ca2+ dependent arachiodonate release and prostaglandin synthesis in expression of the action of osmolality on renal inner medullary guanosine 3'5' monophosphate. AB - The present study examined the effects of osmolality on basal cGMP metabolism and cGMP responses to carbamylcholine in rat inner medulla. The basal cGMP content of inner medullary slices and cGMP responses to carbamylcholine fell as media osmolality was increased from 305 to 1650 mosmole/liter by the addition of urea plus NaCl to standard Krebs bicarbonate buffer. Exclusion of extracellular Ca2+ or addition of tetracaine abolished the effects of both a reduction in osmolality and carbamylcholine to increase cGMP. Readdition of Ca2+ to Ca2+-deprived slices restored the actions of media osmolality and carbamylcholine on cGMP. Ionophore A23187 enhanced the effects of Ca2+ to increase slice cGMP content. Analogous to the effects of Ca2+ alone, increases in cGMP accumulation in response to Ca2+ plus A23187 were significantly suppressed at high osmolality. In slices prelabeled with [14C]-arachidonate, the stimulatory effects of Ca2+ plus A23187 on cGMP were correlated with enhanced release of [14C]-arachidonate into the media and with increased accumulation of prostaglandin E in the media, all of which were depressed in slices incubated at 1650 compared to 750 mosmole/liter. Exogenous arachidonate increased cGMP 50% to twofold in the absence of Ca2+. However, the effects of exogenous arachidonate on cGMP were clearly less than those of either Ca2+ or carbamylcholine. Addition of indomethacin or exclusion of O2 abolished effects of exogenous arachidonate, Ca2+ plus A23187, reduced osmolality, and carbamylcholine to increase cGMP. In the presence of indomethacin or in the absence of O2, Ca2+, and arachidonate-induced prostaglandin E accumulation was also not detectable. By contrast, addition of indomethacin or exclusion of O2 had no effect on Ca2+-induced [14C]-arachidonate release. Changes in cGMP accumulation in inner medulla in response to changes in media osmolality, Ca2+ plus A23187, and exogenous arachidonate were accompanied by directionally similar alterations in cAMP. Moreover, increases in cAMP induced by Ca2+ or arachidonate were inhibited by indomethacin and O2 deprivation. These data suggest that Ca2+-dependent fatty acid release and oxygenation by fatty acid release and oxygenation by cyclooxygenase may participate in the control of the metabolism of both cGMP and cAMP in inner medulla. However, PGE2 and PGI2 increased cAMP but not cGMP, whereas carbamylcholine increased cGMP but not cAMP. Thus, to the extent that arachidonate oxygenation products mediate changes in cyclic nucleotide metabolism in inner medulla, it is likely that more than one product is involved or that changes in cGMP and cAMP occur in separate compartments of inner medulla. PMID- 6251339 TI - Human endothelial cells in vitro. PMID- 6251340 TI - Prospects for growing normal human melanocytes in vitro. PMID- 6251341 TI - Properties of a macrophage cell line transformed by simian virus 40. Morphological changes related to cell functions. AB - A mouse macrophage clone (line nH-1) transformed by simian virus 40 (SV40) was examined by electron microscopy. In the growing phase of the cultures, NH-1 cells were non-phagocytic and SV40 T antigen-positive, and contained a large number of filament sheaths within their pseudopodia. In the late stationary phase, they became phagocytic, SV40 T antigen-negative and contained a filamentous network within their psudopodia. In addition, NH-1 cells in the late stationary phase were very similar to normal macrophages in other morphological properties. PMID- 6251342 TI - Enhanced phagocytic activity of macrohpages in mouse hepatitis virus-infected nude mice. PMID- 6251343 TI - Gene expression of ampicillin resistance transposons, Tn2601 and Tn2602. AB - To establish the mode of gene expression specified by transposon, we investigated the correlation among the homology of the DNA sequence, the extent of transposon specific transcription, the specific activity of penicillinase (PCase) per cell, and the transposition frequency by using two ampicillin resistance transposons (TnAs), Tn2601 and Tn2602. Although both the TnAs specify the so-called type I PCase, Tn2602 always conferred 10- to 20-fold higher PCase activity per cell than Tn2601 regardless of the kind of replicon carrying TnA. The transposition freuency of Tn2602 also was 8 to 50 times higher than that of Tn2601 in all combinations of donor and recipients plasmids examined. As a result, the transposability expressed by the TnA was thought to correlate with the productivity of PCase in the cell specified by the corresponding TnA. The level of TnA-specific transcription of Tn2602 was noticeably higher than that of Tn2601, whereas the two TnAs shared a high degree (more than 90%) of DNA sequence homology. These results suggest that the difference in rates of transcription of the two transposons plays a key role in determining the difference in the productivity of PCase and the transposition-protein(s) of Tn2601 and Tn2602. PMID- 6251344 TI - Effect of oxidizing agents and sulfhydryl group reagents on beta toxin from Clostridium perfringens type C. AB - Purified beta toxin from Clostridium perfringens type C was inactivated by the oxidizing agents o-iodosobenzoate (OIBA), oxidized glutathione, and ferricyanide, and by the sulfhydryl group regents 5,5'-dithio-bis(2-nitrobenzoic acid) (DTNB) and N-ethylmaleimide, iodoacetamide, and iodoacetic acid, causing loss of activity in various degrees depending on the concentration used. The activity of the toxin was not influenced by exposure to 1.0 mM of p-chloromercuribenzoate. The toxin treated by OIBA or DTNB was reactivated by incubation with 2 mercaptoethanol and dithiothreitol. The data suggest that beta toxin contains thiol groups which are essential for the activity. PMID- 6251345 TI - [Removal of the microbial cells from a silica gel layer after their electroretention]. PMID- 6251346 TI - [Characteristics of the course of dysentery in experimental animals infected with a complex of Shigella and adenoviruses]. PMID- 6251347 TI - [Isolation and identification of a coronavirus, the causative agent of transmissible gastroenteritis of swine]. PMID- 6251348 TI - The reversibility of cancer: the relevance of cyclic AMP, calcium, essential fatty acids and prostaglandin E1. AB - Transformed cells in culture can be normalised (made to undergo reverse transformation) by exposure to cyclic AMP, prostaglandin (PG) E1 and certain drugs. One of these drugs, thioproline, has been successfully used in treating human cancer. All cancer cells have a number of common characteristics: they exhibit aerobic glycolysis, they fail to show feedback regulation of cholesterol biosynthesis, they do not regulate cytoplasmic calcium levels normally and they produce excessive amounts of 2 series PGs. It has been known since 1975 that transformed cells cannot make PGE1 because of loss of the delta-6-desaturase enzyme which converts linoleic acid to gamma-linolenic acid. There is evidence that PGE1 acting in concert with thromboxane A2 has effects which make it able to reverse all the metabolic abnormalities common to all cancer cells. It is therefore argued that loss of the ability to make PGE1 and/or thromboxane A2 may be the critical step in malignant change in many forms of cancer. Restoration of normal PGE1 synthesis by providing gamma-linolenic or dihomogammal inolenic acids which will by-pass the blocked desaturase, whould be of value in normalising malignant cells and reversing cancer growth. Since this approach is completely non-toxic it is here seriously suggested that it might be used as a first step in treatment of those cancers where current evidence suggests that delay in the administration of orthodox treatment is unlikely to affect prognosis. PMID- 6251349 TI - A hypothesis for a role for unsaturated fatty acids in electron transport and its potential application to understanding the mitochondrial respiratory chain. AB - Unsaturated fatty acids are required for mitochondrial oxidative phosphorylation and electron transport, though their role has not been determined. We have considered the possibility that unsaturated fatty acids might facilitate electron transfer from non-heme iron to heme iron. Unsaturated fatty acids markedly enhanced the reduction of ferric cytochrome c by ferrous iron. Neither stearic acid nor methyl arachidonic acid were effective suggesting that both a double bond and the carboxylic acid group were essential. Thus unsaturated fatty acids can directly facilitate electron transfer from non-heme iron to heme iron. We hypothesize that unsaturated fatty acids may play a similar critical role in mitochondrial oxidative phosphorylation and other biological processes where rapid electron transfer occurs. PMID- 6251350 TI - Progressive patterns in breast diseases. PMID- 6251351 TI - Primary liver cancer in Malaysian children. PMID- 6251352 TI - [Does the "pill" promote the development of tumors?]. PMID- 6251353 TI - [Changing emphasis in nuclear medical diagnosis of kidney diseases]. PMID- 6251354 TI - [Analysis of islet cell tumors]. PMID- 6251355 TI - [Neurological, psychological and physical complications in alcoholics]. PMID- 6251356 TI - Neurotensin binding to extraneural and neural receptors: comparison with biological activity and structure--activity relationships. PMID- 6251357 TI - Adenosine-induced alterations in the adenosine 3':5'-monophosphate levels in mammalian epidermis. PMID- 6251358 TI - Ouabain-induced changes in the tertiary and the quaternary conformations of (Na+ + K+)-activated adenosine triphosphatase. PMID- 6251359 TI - Inhibition of fibroblast cyclic AMP escape and cyclic nucleotide phosphodiesterase activities by xanthines. PMID- 6251360 TI - Effect of adrenergic amines on phosphatidylinositol labeling and glycogen synthase activity in fat cells from euthyroid and hypothyroid rats. PMID- 6251362 TI - Comparative analysis of proteins selectively released from cell nuclei of different eukaryotic species under conditions of mild hydrolysis by nucleases. AB - Nuclei of cultured Chinese hamster fibroblasts, dechoryonized eggs of Drosophila melanogaster, calf thymocytes and mouse spleen were digested with micrococcal nuclease or DNAse I under conditions when about 15-20% of nuclear DNA is hydrolyzed. Proteins released from the nuclei with this DNA were analyzed by electrophoresis in polyacrylamide gels in the presence of SDS and the most prominent components were purified in each case. It is shown that these components derived from different species have different electrophoretic mobilities but are very similar in the amino acid composition characterized by high glycine content and a low lysine/arginine ratio. Molecular weights of two of those components, from mouse spleen and thymocytes, were estimated and are shown to be 25,500 and 23,000, respectively. Notwithstanding their different molecular weights they have the same N-terminal amino acid--arginine. PMID- 6251363 TI - The cytochemical bioassay of polypeptide hormones. PMID- 6251361 TI - Inhibitors of the GABA uptake systems. AB - This review describes a novel class of heterocyclic GABA uptake inhibitor with no affinity for the GABA receptors. The parent compound nipecotic acid is a potent inhibitor of neuronal and glial GABA uptake, and nipecotic acid is a substrate for the transport carriers concerned. The structurally related cyclic amino acids guvacine and cis-4-hydroxynipecotic acid are also potent inhibitors of both GABA transport systems. Even minor structural alterations of these compounds result in considerable or complete loss of activity. Whereas homonipecotic acid is a weak but selective inhibitor of glial GABA uptake, homoguvacine is virtually inactive. Similarly the lower homologues of nipecotic acid and guvacine, beta-proline and 3 pyrroline-3-carboxylic acid, respectively, show some selectivity with respect to inhibition of glial GABA uptake, but these compounds are much weaker than the parent compounds. The bicyclic compounds THPO and THAO, in which the carboxyl groups of nipecotic acid and homonipecotic acid have been replaced by 3 isoxazolol units are moderately potent and practically specific inhibitors of glial GABA uptake. cis-4-Mercaptonipecotic acid is considerably weaker than the closely related analogue cis-4-hydroxynipecotic acid, but the former compound may interact irreversibly with the GABA transport carriers. The results demonstrate a pronounced substrate specificity of the glial and in particular the neuronal GABA transport system. It is evident that the GABA molecule is transported in a conformation different from that, in which it activates its receptors. These findings are of importance for the development of drugs for selective pharmacological regulation of the functions of central GABA-mediated synapses in certain neurological diseases. PMID- 6251364 TI - Ca-activated neutral protease and its inhibitors: in vitro effect on intact myofibrils. AB - SDS gel electrophoresis of troponin and myosin extracted from chicken myofibrils pretreated with Ca-activated neutral protease showed a pattern similar to that observed in the muscles of patients with Duchenne muscular dystrophy, that is, a decrease in troponin-I and troponin-C with relative preservation of troponin-T and degradation of the heavy chain of myosin. Also, alpha-actinin and troponin-C were released from myofibrils. Two inhibitors of Ca-activated neutral protease, leupeptin and E-64, inhibited the degradative action of Ca-activated neutral protease on intact myofibrils in vitro. PMID- 6251366 TI - Mediators of immediate hypersensitivity derived from arachidonic acid. PMID- 6251365 TI - Phenytoin therapy of recessive dystrophic epidermolysis bullosa. Clinical trial and proposed mechanism of action on collagenase. AB - We administered phenytoin (diphenylhydantoin) by mouth to 17 unselected patients to assess its ability to reduce blistering in recessive dystrophic epidermolysis bullosa (RDEB). Therapeutic response was correlated with blood levels of the drug. Although there was a decrease in blistering of 53 +/- 6 per cent (mean +/- S.E.) among all patients at levels of more than 8 microgram of phenytoin per milliliter, the response was variable, with 12 of 17 patients having a decrease in blistering of more than 40 per cent. Since increased collagenase in human skin has been implicated in the pathogenesis of blistering in RDEB, we examined the effect of phenytoin on this enzyme. Although the drug did not inhibit collagenase activity directly, its addition to human-skin explant and fibroblast cultures produced a 50 to 60 per cent decrease in collagenase activity and immunoreactive protein concentrations. These in vitro studies suggest that phenytoin inhibits synthesis or secretion of collagenase of both, and that the favorable clinical response can be explained by this inhibition. PMID- 6251367 TI - Absorption of whole peanuts, peanut oil, and peanut butter. PMID- 6251369 TI - Management of Zollinger-Ellison syndrome. PMID- 6251368 TI - Current concepts. Biochemical markers in lymphoid malignancy. PMID- 6251370 TI - Molecular epidemiology of cytomegalovirus infections in women and their infants. AB - We studied cytomegaloviruses (CMV's) isolated from mothers and their children to determine whether recurrent infections and transmission to the fetus in immune women are due to reinfection or reactivaton of endogenous virus. Twenty-one strains of CMV from six mother-baby pairs, from two congenitally infected siblings, and from repeat isolates from four women were examined for genetic relatedness, by means of restriction endonuclease analysis of purified viral DNA. Although CMV's from unrelated persons were always different, strains from five to six congenitally infected babies were identical or very closely related to those from their mothers. Strains from congenitally infected siblings were also concordant, as were repeat isolates form three of four women. Major differences in viral DNA were detected in strains recovered from the same woman or from a mother-baby pair in only two cases. Endogenous CMV appears to be most frequent source of recurrent infection and intrauterine transmission in immune women; reinfection also occurs, but less commonly. PMID- 6251371 TI - Human T-cell cultures from virus-sensitized donors can mediate virus-specific and HLA-restricted cell lysis. PMID- 6251372 TI - Lamarckist revival in immunology. PMID- 6251373 TI - Strategies of drug resistance in herpes simplex. PMID- 6251374 TI - Nucleotide sequence of the yeast plasmid. AB - The nucleotide sequence of the yeast DNA plasmid (2 mu circle) from Saccharomyces cerevisiae strain A364A D5 has been determined. The plasmid contains 6,318 base pairs, including two identical inverted repeats of 599 base pairs. Possible functions are suggested, and attributes of an improved vector for cloning foreign DNAs in yeast are discussed. PMID- 6251375 TI - Insulin trigger, cyclic AMP-dependent activation and phosphorylation of a plasma membrane cyclic AMP phosphodiesterase. AB - Regulation of blood glucose levels by the liver is primarily achieved by the action of two peptide hormones, insulin and glucagon, which bind to specific receptors associated with the hepatocyte plasma membrane. Whilst the molecular action of glucagon at the level of the cell plasma membrane in activating adenylate cyclase is relatively well understood, we know little, if anything, of the molecular consequences of insulin occupying its receptor. We demonstrate here that insulin, at physiologically relevant concentrations, can trigger the cyclic AMP-dependent activation and phosphorylation of a low Km cyclic AMP phosphodiesterase attached to the liver plasma membrane. Such an effect may in part explain the ability of insulin to inhibit the increase in cellular cyclic AMP content that glucagon alone produces by activation of adenylate cyclase. Our observation that basal, intracellular cyclic AMP levels are insufficient to allow insulin to activate the cyclic AMP phosphodiesterase, yet those cyclic AMP levels achieved after exposure of the cells to glucagon are sufficient, gives a molecular rationale to Butcher and Sutherland's proposal that it is necessary to first elevate cellular cyclic AMP levels before they can be depressed by insulin. PMID- 6251376 TI - The acetylcholine receptor. PMID- 6251377 TI - Enkephalin blocks inhibitory pathways in the vertebrate CNS. PMID- 6251378 TI - Role of corticosteroid-binding globulin in interaction of corticosterone with uterine and brain progesterone receptors. AB - The central actions of the steroid hormone progesterone remain an enigma. However, there is no doubt that this hormone has a vital role in the control of sexual function and behaviour in many species, including man. Furthermore, progesterone may be involved in the premenstrual and postpartum syndromes. It would therefore be very useful to know the role and mechanism of action of progesterone in the brain. We now show that there are differences between progesterone receptors in brain and uterus, and possibly in the distribution of the serum progesterone-binding protein, corticosteroid-binding globulin (CBG), which may enter uterine but not brain cells. PMID- 6251379 TI - Action of formamidine pesticides on octopamine receptors. AB - The formamidines are a structurally novel group of pesticides of growing importance in the control of mites, cattle ticks and certain orders of insects which have become resistant to conventional acaricides and insecticides. Their mode of action is complex with dose-dependent lethal and subletahal effects. At sublethal levels they cause behavioural changes in the target pest species (for example in feeding and in mating behaviours), changes which are responsible for the protective effects on crops and livestock. Although many suggestions have been made for the underlying biochemical mechanism, including inhibition of monoamine oxidase activity, uncoupling of respiration and blockade of neuromuscular transmission, no direct evidence has been presented. Another possibility is interaction with octopamine receptors in the central nervous system. We report here that the formamidine acaricide/insecticide, chlordimeform (CDM), and its demethylated deivative can mimic the actions of octopamine at the locust neuromuscular junctions. This gives the clearest evidence to date of the site of action of the formamidines and indicates a novel mode of action for these pesticides. PMID- 6251380 TI - The sodium channel and intracellular H+ blockage in squid axons. AB - Sodium channels in plasma membranes can be blocked by a large variety of toxins and local anaesthetics. This property, however, is not confined to relatively large molecules. For instance, extracellularly applied small ions like hydrogen may also prevent the passive transport of permeant cations across open Na+ channels. A typical feature of this phenomenon is that the blocking action of hydrogen is gradually relieved by increasing the voltage applied across the membrane. Although in the frog skeletal muscle there is no clear evidence for a similar intracellular action, we report here for the squid giant axon remarkable effects on the ionic permeability of Na+ channels when the internal perfusate contains an excess of protons. Analysing the action of low pH inside and outside the fibre in terms of a kinetic model, we could conclude that Na+ channels in squid axons are controlled by two independent groups: one with an apparent pKa of 4.6 and the other with pKa 5.8, the former feeling one-fifth of the applied membrane potential, the latter three-quarters. As with pharmacological agents, we also show that the voltage-dependence of the H+ blockage is not affected by the presence of the inactivation gate. PMID- 6251381 TI - In vitro tumorigenic transformation by a defined sub-genomic fragment of bovine papilloma virus DNA. PMID- 6251382 TI - Calcium-dependent phosphorylation of histone H3 in butyrate-treated HeLa cells. AB - Ca2+ is prominant in the control of cell proliferation and function. However, the biochemical mechanism(s) mediating its effects on nuclear events is unknown. We report here that Ca2+, at physiological concentrations, stimulates the phosphorylation of histone H3 by an endogenous protein kinase in HeLa cell nuclei. Also, pretreatment of cells with Na butyrate, which increases histone acetylation, selectively increases the susceptability of histone H3 to phosphorylation by the protein kinase. Our results reveal a potential link between histone H3 acetylation and phosphorylation, modifications which are thought to have important effects on chromatin structure and function and suggest a possible mechanism whereby stimuli at the cell surface (such as hormones, mitogens and drugs) may influence biochemical events at the nuclear level; changes in the intracellular Ca2+ concentration may influence the phosphorylation of chromosomal proteins, mediated by Ca2+ -dependent kinases in th nucleus. PMID- 6251383 TI - The putative mRNA for subunit II of human cytochrome c oxidase starts directly at the translation initiator codon. AB - The gene for subunit II of cytochrome c oxidase (COII) in human mitochondrial DNA (mtDNA) is immediately contiguous, on its 5'-end side, to a tRNAAsp gene. Since all eukaryotic mRNAs so far analysed have been shown to have a noncoding stretch, which is presumably used for ribosome attachment on the 5'-side of the coding sequence, it was resonable to ask whether, in the case of the human COII mRNA, the above function is performed by the tRNAAsp sequence or a portion of it, or whether this mRNA lacks a 5' noncoding stretch. We have sequenced a 5'-end proximal segment of the putative COII mRNA from HeLa cells of about 30 nucleotides and have aligned it with the COII coding sequence in human mtDNA. Our results show that this RNA starts directly at the AUG initiator codon. PMID- 6251384 TI - Structural and functional diversity in 4-alpha-helical proteins. AB - Protein crystallographic studies show that many structural arrangements appear as common features among proteins which are otherwise unrelated in sequence or function. One of the more recently recognized recurring protein structural motifs is a nearly parallel arrangement of four alpha-helices to form a sequentially connected left-twisted bundle. We describe here the geometrical properties of these structures and suggest how they relate to the functional and aggregate properties of these molecules. PMID- 6251385 TI - [Current understanding of the etiology of colonic carcinoma]. PMID- 6251386 TI - [Dietary fiber, useless ballast or necessary component?]. PMID- 6251387 TI - [Fiber in the diabetic diet]. PMID- 6251388 TI - [Fiber in the diabetic diet]. PMID- 6251389 TI - Effect of volume expansion on nephrogenous cyclic AMP during vena cava constriction in the dog. PMID- 6251390 TI - [Intraneural synovial cyst in the peroneal nerve. Case report (author's transl)]. AB - The authors report one case of paralysis of the peroneal nerve due to an intraneural synovial cyst, in connection with the superior tibio-fibular joint. After an anatomic work and a complete revue of the literature, etiopathogenic and diagnostic problems seem to be resolved, and this justifies their terminologic choice. PMID- 6251391 TI - [Electromyographic study of mentalis muscle reaction to pain]. AB - Three types of muscular reaction to pain were distinguished. Type I--a defensive reaction to a noxious stimulus, type II--muscular guarding at the site of pain, type III--suffering expression. The third type includes reaction of facial muscles discernible only at high pain intensity in subjects with hypersensitivity to pain. In a search for this reaction in all pains electromyographic investigations of the mentalis muscle were carried out since their connection with nociceptive stimulation is made use of in the sign of Marinesco-Radovici. In 18 out of 20 patients with sciatic pain spontaneous activity was observed in the mentalis muscle. Intensification of pain caused by nerve stretching (straight-leg raising test) evoked activity of these muscles in all studied patients and its intensity was higher. The observed reaction may be an objective evidence of suffering. PMID- 6251392 TI - [Disorders of neuromuscular transmission in hyperthyroidism]. AB - Using the method of supramaximal electrostimulation 35 hyperthyroid patients with signs of muscle weakness or muscular fatigability were investigated and in over half the cases (53.5%) disturbances of neuromuscular transmission were found using sufficiently sensitive methods of activation. In nearly 70% of the tested muscles stimulated at 10 Hz a fall of the amplitude of successive potentials was observed. The analysis of these results suggested the following conclusions: 1. Muscular fatigability in hyperthyroidism is reflected in electrophysiological findings. 2. A comparison of hyperthyroidism with myasthenia showed that similarities and differences exist in the electrophysiological findings between both groups. 3. An additional, besides disturbances of neuromuscular transmission, factor determining muscular fatigibility in hyperthyroidism is probably damage to the muscle fibre. PMID- 6251393 TI - Nuclear inclusions in Alzheimer's disease. AB - Biopsy samples of parietal cortex from seven patients undergoing atrio ventricular shunt operations have been examined electron microscopically. Five were suffering from Alzheimer's disease, while two were subjects with normotensive hydrocephalus following previous head injuries. Intranuclear neuronal, inclusions of three types were found. Most frequent was the intranuclear rodlet, which was commonly observed in four of the patients with Alzheimer's disease, but in one block only from one of the hydrocephalus cases. The other two types, namely the spherical inclusion body and the vermicellar-like inclusion, were found less commonly and in only two cases. No inclusions were seen in glial nuclei. PMID- 6251394 TI - Adrenal regeneration. Time course, effect of hypothalamic hemi-islands and response to unilateral adrenalectomy. AB - Regeneration of rat adrenals was studied after bilateral enucleation to determine whether there is a neural component mediating this process as there is in compensatory adrenal growth after unilateral adrenalectomy. Regeneration was approximately 50% complete (based on criteria of wet weight and DNA content) by 10 days after enucleation; at this time circulating ACTH levels were twice as high in enucleates as in sham-operated controls, but corticosterone levels were normal. Regeneration was apparently complete at sometime between 3 and 6 weeks and circulating ACTH and corticosterone levels were normal at these times compared to controls. Unilateral adrenal enucleation resulted in compensatory growth of the opposite gland, not regeneration of the enucleated gland. Unilateral hypothalamic hemi-islands made with a Halasz knife resulted in bilateral augmentation of adrenal regeneration at 10 days and 6 weeks. From these results we conclude that adrenal regeneration after bilateral enucleation occurs by different afferent and efferent mechanisms than compensatory adrenal growth after unilateral adrenalectomy. Additional studies were performed in rats 3 and 6 weeks after adrenal enucleation to test whether the adrenal medulla participates either in compensatory adrenal growth or in the augmented ACTH response to ether vapors observed in unilaterally adrenalectomized rats. Normal compensatory adrenal growth occurred 3 days after unilateral adrenalectomy in rats bilaterally enucleated 6 weeks earlier. Prior enucleation did not inhibit the increased ACTH response of unilaterally adrenalectomized rats to ether. Therefore, the adrenal medulla does not mediate compensatory adrenal growth or the augmented ACTH response of unilaterally adrenalectomized rats to ACTH-releasing stimuli. PMID- 6251395 TI - ACTH regulation of tissue-CRF. AB - The influence of the anterior pituitary on tissue CRF was investigated in two sets of experiments using lesioned, hypophysectomized, adrenalectomized donor rats. Donors were injected with 1 or 0.5 anterior pituitary equivalents 3 h before transfer of plasma to recipient animals. Injection of 1 pituitary equivalent significantly reduced levels of corticosterone in recipient rats compared to saline injection at 3 different time intervals following the transfer. In a second series of experiments donor animals received replacement with saline, ACTH, TSH, or PRL at 0, 2 and 4 h following adrenalectomy; transfer of plasma to recipient animals was at 5 h. Of the three hormones injected only ACTH significantly reduced tissue CRF activity in donor animals. Recipients of these donors showed suppressed levels of corticosterone compared to recipient animals whose donors were injected with saline, TSH or PRL. The ACTH dose response curve indicates that the effective dose for suppression of tissue CRF in donor animals is in the range of 1-10 mU/ml. Results of these experiments clearly show that tissue CRF is inhibited by the anterior pituitary hormone ACTH rather than by elevated levels of corticosterone. These experiments suggest that feedback regulation of tissue CRF release by ACTH may occur in response to prolonged physical stress. PMID- 6251396 TI - Microsurgical relationships of the anterior inferior cerebellar artery and the facial-vestibulocochlear nerve complex. AB - The relationship of the anterior inferior cerebellar artery (AICA) to the facial (7th) and vestibulocochlear (8th) nerves was studied using 3x to 20x magnification in 50 cerebellopontine angles (CPAs) from 25 adult cadavers. The AICA originated from the basilar artery as a single (72% of the CPAs), duplicate (26%), or triplicate (2%) artery. Each of the 50 CPAs had one or more arterial trunks that coursed in close proximity to the 7th and 8th cranial nerves and thus were said to be nerve-related. The nerve-related arterial trunks were divided into three segments based on their relationship to the nerves and meatus: the premeatal, meatal, and postmeatal segments. The meatal segment projected to the meatus or into the canal in 64% of the CPAs. In relation to the nerves, the premeatal segment was most commonly anteroinferior, the meatal segment was inferior, and the postmeatal segment was posteroinferior. The nerve-related branches of the AICA gave rise to internal auditory arteries in 100% of the 50 CPAs, recurrent perforating arteries in 82%, and the subarcuate artery in 72%. The internal auditory and recurrent perforating arteries arose most commonly from the premeatal segment, and the subarcuate artery arose most commonly from the postmeatal segment. There were one to four internal auditory arteries per CPA, zero to three recurrent perforating arteries, and zero or one subarcuate artery. The effects of occlusion of the nerve-related arteries and their involvement in conditions treated by neurosurgeons are reviewed. PMID- 6251397 TI - Glioblastoma multiforme occurring 13 years after treatment of a medulloblastoma. AB - Although medulloblastoma is said to be capable of astrocytic differentiation, the development of an astrocytic neoplasm in association with a medulloblastoma is extremely rare. We report the light and electron microscopic features of a supratentorial glioblastoma that occurred 13 years after radiation therapy for a cerebellar medulloblastoma. The diverse ultrastructural features of the glioblastoma may reflect the multipotentiality of the cells in medulloblastoma. An alternate interpretation is that the glioblastoma represents a radiation induced neoplasm after therapy for a medulloblastoma. PMID- 6251398 TI - Hypoxic cell radiosensitizers in the treatment of malignant brain tumors. AB - Radiation therapy provides the most effective adjuvant treatment for patients with malignant brain tumors, but brain intolerance to potentially curative doses of radiation is limiting. Solid tumors are thought to contain a substantial population of cells that are hypoxic; because much of the cell kill caused by ionizing radiation is the result of an oxygen-dependent, free radical-mediated attack on deoxyribonucleic acid, hypoxic tumor cells are known to be radioresistant and are therefore a barrier to cure. With the hope of improving the therapeutic ratio of brain tumor radiation therapy, hypoxic cell radiosensitizers are being evaluated. Two nitroimidazoles, metronidazole and misonidazole, have received the most attention. These compounds are thought to mimic oxygen by "fixing" the free free radical-induced damage caused by radiation in tumor cells. Clinical trials ae providing considerable information about the pharmacokinetics and toxicities of these agents. The preliminary results obtained in clinical trials with brain tumor patients are somewhat discouraging; drug toxicity limits the number of radiation treatments with which a sensitizer may be given. The results of ongoing clinical trials with metronidazole and misonidazole and the identificiation of new, less toxic hypoxic cells sensitizers may improve the potential for this modality of therapy. PMID- 6251399 TI - Reversible osmotic blood-brain barrier disruption in humans: implications for the chemotherapy of malignant brain tumors. AB - The blood-brain barrier seems to be an important factor in drug access to malignant brain tumors. Successful experimental reversible disruption of the blood-brain barrier in animals provided the basis for a clinical evaluation of osmotic disruption in five patients with primary and metastatic malignant brain tumors. Good to excellent blood-brain barrier disruption was achieved in four patients with a single nontransient complication, a superficial wound infection at the burr hole site in the first patient. Reversible, transient osmotic barrier disruption was achieved 15 times in five patients without additional toxicity. Computed tomography and radionuclide brain imaging were shown to be useful noninvasive monitors of the adequacy and extent of barrier disruption. These studies also provide further evidence that the barrier is at least partially intact in human tumors because in one patient a metastsis was seen only after barrier disruption. PMID- 6251400 TI - Mechanisms of disturbance in neuromuscular transmission in rats with alloxan diabetes. PMID- 6251401 TI - Interaction between hypophyseal-adrenal and genital system in silver foxes. PMID- 6251402 TI - Identification of additional histaminergic neurons in Aplysia: improvement of single cell isolation techniques for in tandem physiological and chemical studies. PMID- 6251403 TI - Effect of apamin on the electrical responses of smooth muscle to adenosine 5' triphosphate and to non-adrenergic, non-cholinergic nerve stimulation. PMID- 6251404 TI - Monoaminergic synapses in infant mouse neocortex: comparison of cortical fields in seizure-prone and resistant mice. PMID- 6251405 TI - Effect of alpha-bungarotoxin on retinotectal synaptic transmission in the goldfish and the toad. PMID- 6251406 TI - Fatal infantile mitochondrial myopathy and renal dysfunction due to cytochrome-c oxidase deficiency. AB - A 1-month-old boy was admitted because of failure to thrive. He was floppy and had bilateral ptosis, diminished reflexes, and poor suck. He had aspiration pneumonia, developed seizures, and died at age 3 1/2 months. Laboratory data showed lactic acidosis, proteinuria, glycosuria and generalized aminoaciduria. He was an only child, and family history was negative. Muscle biopsy showed large clumps of granules positive with oxidative enzyme stains and increased lipid droplets. Ultrastructural studies showed large aggregates of mitochondria, many of which were greatly enlarged and contained disoriented or concentric whorls of cristae and paracrystalline inclusions. Cytochrome c oxidase was absent in fresh frozen sections by histochemical staining. By biochemical assay, cytochrome c oxidase (cytochrome aa3) was 6% of normal in muscle biopsy and undetectable in autopsy muscle; spectra and content of cytochromes showed lack of cytochrome aa3, decreased cytochrome b and normal cytochrome cc1. In kidney, cytochrome-c-oxidase activity was 38% of normal and spectra showed decreased cytochromes aa3 and b. The association of fatal infantile mitochondrial myopathy, lactic acidosis and renal dysfunction was previously reported by Van Biervliet et al and appears to be a distinct nosologic entity, one of the few biochemically defined mitochondrial myopathies. PMID- 6251407 TI - CSF "monoclonal" bands in chronic relapsing polyneuropathy. AB - The characteristics and temporal profiles of cerebrospinal fluid (CSF) and serum immunoglobulin patterns on agarose gel electrophoresis were studied in 47 patients with acute idiopathic polyneuropathy (AIP) and 15 patients with chronic relapsing polyneuropathy (CRP). Nineteen of 47 patients with AIP had transient oligoclonal IgG bands, which disappeared when the neurologic signs subsided. By contrast, 14 of 15 patients with CRP had a "monoclonal" (single) IgG band, which (1) was unchanged on repeated CSF examinations over 18 months, (2) was unaffected by corticosteroid therapy, and (3) did not correlate with the severity or chronicity of the disease. Serum protein patterns and in situ central nervous system IGG synthesis and IgG:albumin index were normal in the CRP patients. The origin of the band and the nature of the putative antigen(s) that the band may be directed against were not identified. Our findings suggest that different immunopathogenic mechanisms may be operating in CRP, compared with AIP. The stable IgG band in CRP may reflect response to a persisting antigenic stimulation and, with further experience, may prove to be of prognostic significance by furnishing early in the illness: (1) a clue to the subsequent course of the disease, and (2) possible guidance on therapeutic decisions. PMID- 6251408 TI - [Adenosine cyclic monophosphate level, adenyl cyclase activity, 3,5'-cyclic AMP phosphodiesterase and protein kinases in rat brain in experimental carbon monoxide poisoning]. PMID- 6251409 TI - Case report: false aneurysm due to synovial sarcoma. AB - On the basis of a false aneurysm of the radial artery caused by a synovial sarcoma, the behavior and histology of this fairly rare tumor are discussed. There are no reports in the literature which record such a rapidly developing synovial sarcoma as that observed in the patient described here. PMID- 6251410 TI - Proton beam irradiation. An alternative to enucleation for intraocular melanomas. AB - Proton irradiation was used in the treatment of uveal melanomas in 36 eyes. The average follow-up period was 16 months. One patient developed metastatic disease and died. No eye has been enucleated and tumor regression has been observed in all 22 eyes with a follow-up of more than 12 months. This type of treatment offers definite advantages over previously used methods, can be used for the treatment of relatively large melanomas, and should be considered before enucleation. PMID- 6251411 TI - Pathology and computed tomography. AB - Although computed tomography (CT) has been an explosive development over the past several years resulting in great improvement in the preoperative localization of orbital tumors and other pathologic processes, it has its limitations in terms of providing specific histologic diagnoses. The cases selected for this presentation illustrate some of these limitations, and some of the lessons learned from our experiences during the past few years. PMID- 6251412 TI - The control of bacterial contamination in carcass meal with propionic acid. AB - The effect of the addition of 2, 3, 5, 7 and 10% respectively of propionic acid on known numbers of bacteria added to or contained in carcass meal was examined. Escherichia coli was totally inhibited by 2% propionic acid, while 5% of the acid both inhibited Salmonella typhimurium and brought about a 74,7% reduction in the total aerobic bacterial count. PMID- 6251413 TI - Turkey meningo-encephalitis in South Africa. AB - Turkey meningo-encephalitis is a neuroparalytic disease of turkeys first described and shown to be caused by a flavivirus in Israel. During 1978 a similar disease was observed in South Africa. In addition to the lesions described in Israel, myocarditis, regression of the ovary and egg peritonitis were constant findings. The similarity in host range, symptoms and pathological changes produced by the virus isolated locally and in Israel and the serological cross reaction between the 2 virus isolates indicate that they are identical. PMID- 6251414 TI - [Specific delayed hypersensitivity to Epstein-Barr virus: in vitro study by leukocyte migration inhibition]. PMID- 6251415 TI - [Congenital cytomegalic disease]. PMID- 6251416 TI - [What is your diagnosis?]. PMID- 6251417 TI - Sacrococcygeal paciniomas. AB - Two well differentiated pure Paciniomas, bearing no resemblance to neurofibromas, were resected from infants with spinal deformities. Each was in the form of a thick cord running from a sacral dimple through a low occult spina bifida to the spinal dura. The lesions are considered to be a malformation or hamartomatous overgrowth. Control sacrococcygeal regions from necropsies on 15 infants were examined histologically, and Pacinian corpuscles were found in 7, usually near the tip of the coccyx, and never numerous. PMID- 6251418 TI - [Role of prostaglandins, thromboxanes and prostacyclin in regulating the thrombocyte aggregation process and liberation reaction normally and in pathology]. PMID- 6251419 TI - Hormone-stimulated cyclic AMP production by skin fibroblasts cultured from healthy persons and patients with cystic fibrosis. AB - The experiments reported here illustrate a few of the factors apart from genes which can influence hormone-responsive generation of cyclic adenosine 3':5' monophosphate in human fibroblasts. For both normal and cystic fibrosis fibroblasts, the isoproterenol stimulation ratio was maximal 2 to 3 days after subculture and declined thereafter; prostaglandin E1 stimulation ratio was maximal 7 to 10 days after subculture. Cells dislodged from the plate by either scraping or typsinization had reduced isoproterenol or prostaglandin E1 stimulation ratios compared to cells studied in situ. Fibroblasts from healthy controls and cystic fibrosis patients plated simultaneously and grown in three different culture conditions responded similarly to the change in growth conditions. Addition to the incubation medium of polyamines, calcium, magnesium, or guanosine triphosphate did not alter the stimulation ratios for isoproterenol or prostglandin E1. Repeated measures analysis indicates that cellular content of cyclic adenosine 3':5'-monophosphate is not a reliable measure for comparing cell lines; isoproterenol stimulation ratio is a reliable measure, but there is large variation from cell line to cell line. Isoproterenol stimulation ratio was the same for normal and cystic fibrosis fibroblasts in each of the three culture conditions tested at both three and ten days after subculture. PMID- 6251420 TI - Adenosine deaminase deficiency without immunodeficiency: clinical and metabolic studies. AB - A child diagnosed at birth as deficient in red blood cell adenosine deaminase (ADA) but with substantial residual lymphocyte ADA has been evaluated for two and one-half years. The only immunologic abnormality observed was hypogammaglobulinemia during the fifth month of life. This was unexpected because children with total ADA deficiency either have severe combined immunodeficiency or selectively greater impairment of cellular than humoral immunity. The absence of severe combined immunodeficiency in this child was associated with normal lymphocyte content of ATP, dATP, and cyclic 3'5'-adenosine monophosphate, potentially toxic metabolites which are elevated in ADA-deficient immunodeficient children. PMID- 6251421 TI - Phosphatidic acid phosphohydrolase and phospholipids in tracheal and amniotic fluids during normal ovine pregnancy. AB - Samples of amniotic fluid and fetal tracheal fluid were obtained from 36 ovine pregnancies which were studied either acutely or chronically during the last two thirds of gestation (65 to 149 days). The specific activity of phosphatidic acid phosphohydrolase (PAPase), disaturated lecithin (DS-L), total phospholipids (TLP) and the L/S ratio were assayed in the amniotic and tracheal fluids. There was a significant and progressive increase in the specific activity of PAPase in tracheal fluid beginning after 110 days, increasing from 66+/- 7 nmoles phosphate released X mg-1 protein x hour-1 (Mean +/- S.E.M.) less than or equal to 110 days, to 107 +/- 6 at 111 to 120 days, and to 277 +/- 70 at 131 to 144 days. The rise in PAPase specific activity was followed by a parallel rise in the DS-L fraction of the TPL (DS-L/TPL ratio), increasing from a DS-L/TPL ratio of 0.06 +/ 0.-1 in fetuses less than or equal to 120 days, to 0.29 +/- 0.06 at 121 to 130 days, and to 0.50 +/- 0.18 at 131 +/- 135 days. The PAPase specific activity and the L/S ratio in amniotic fluid did not change during pregnancy. Neonatal respiratory distress syndrome is the result of inadequate production of surface active material by the fetal and neonatal lung. The enzyme PAPase occupies a central role in the biosynthesis of the glycerophospholipids, and increases in the specific activity of PAPase in human amniotic fluid and in fetal rabbit lung tissue precede or are parallel with the increase in the L/S ratio and pulmonary surfactant synthesis, respectively. We have shown that this sequence is also demonstrable in ovine fetal tracheal fluid, thus providing an animal preparation in which the formation and regulation of surfactant biosynthesis during fetal lung maturation can be investigated in vivo. PMID- 6251422 TI - Aldosterone in vitro restores nephron Na-K-ATPase of distal segments from adrenalectomized rabbits. AB - Aldosterone, when added in vitro to defined nephron segments, dissected from adrenalectomized rabbits, restores the depressed Na+-K+-ATPase activity in the thick ascending limb of the loop of Henle and in the cortical collecting tubule within 1 h of incubation. The direct effect is specific and, as demonstrated for the cortical collecting tubule, dose-dependent. The time course of aldosterone mediated Na+-K+-ATPase activation is compatible with the conjecture of changes in the enzyme lipid environment. PMID- 6251423 TI - K efflux through inward rectifying K channels in voltage clamped Purkinje fibers. AB - The 42K efflux was measured in voltage clamped sheep Purkinje fibers. The voltage dependence of the K efflux can be described as N-shaped, showing a negative slope region. At potentials negative to -30mV, the K efflux is largely due to K flowing through a channel which rectifies in the inward direction and which is blocked by external application of 20mM Cs+. At potentials positive to -30mV an outward rectifier dominates the shape of the K efflux-voltage relationship. This component is insensitive to short external application of Cs+. Both components were also found when Na+ was replaced by tetramethylammonium. When the steady state current-voltage relationship is compared with the K efflux one can conclude that the outward rectifying K flux largely determines the shape of this curve at positive membrane potentials, while the negative slope region of the K efflux correlates with the negative slope of the steady-state current-voltage relation. The K efflux is only slightly enhanced by stimulation of the preparation, corroborating the finding of inward-going rectification of the K channel. A clamp program repetitively activating the positive dynamic current e.g. by alternating the membrane potential between -70 and +10mV, increases the K efflux by about 50% as compared to the efflux measured in steady-state at this positive membrane potential. 4-Aminopyridine suppresses both this extra K efflux and the positive dynamic current. It is concluded that K ions contribute to the positive dynamic current. PMID- 6251424 TI - Blocking action of intracellularly injected neuraminidase on central synapses in vivo. AB - The effect of neuraminidase on synaptic transmission was studied at cholinergic and noncholinergic contacts in the buccal and cerebral ganglion of Ap]lysia. The amplitudes of monosynaptic unitary postsynaptic potentials generated by intracellular stimulation of identified presynaptic neurones were measured as indication for the efficacy of synaptic transmission. Neuraminidase was either intrasomatically injected into a presynaptic neurone, or the whole ganglion was incubated with the enzyme. Intrasomatic injection of the enzyme resulted in complete failure of synaptic transmission. This effect occurred independently of the transmitter used. The synaptic failure was presynaptic in origin. The biophysical characteristics of an injected neurone, particularly the amplitude and propagation of its action potential, did not appear to be affected by neuraminidase. Synaptic transmission and biophysical membrane properties were unaffected by extracellular neuraminidase. We conclude that the synaptic blockade is due to the enzyme's action inside the presynaptic nerve ending. It seems most likely that neuraminidase cleaves sialic-acid-containing-compounds associated with the nerve terminal surface membrane, probably thus causing failure of transmitter release. PMID- 6251425 TI - The effect of histamine on the smooth muscle cells of the ear artery of the rabbit. AB - Histamine activates both H1- and H2-receptors in the ear artery of the rabbit. The specific action of these receptor activations on the membrane potential and the force development has been investigated by using the H1-blocking agent mepyramine and the H2-blocking agent cimetidine. H1-activation depolarizes and increases force development, while H2-activation hyperpolarizes and reduces force development. These effects on the force development can occur independently of the changes of the membrane potential. By determining the effect of histamine on tissues which were denervated with 6-hydroxydopamine it was shown that histamine exerts its effect directly on the smooth muscle cells. Na-deficiency depolarizes the smooth muscle cells, but it also reduces the changes of the membrane potential and the force development induced by H1-stimulation. K-free medium prevents the hyperpolarizing effect of H2-activation. As far as the ion fluxes are concerned an H1-activation is found to induce an increased efflux of K while a simultaneous H2-activation only reduces the increase of flux induced by H1 activation. H1-activation induces a release of Ca from the intracellular Ca stores, while H2-activation inhibits this release. PMID- 6251426 TI - Interaction of lidocaine and benzocaine in blocking sodium channels. AB - 1. Single myelinated nerve fibres of the frog, Rana esculenta, were investigated in voltage and current clamp experiments at pH 7.2 2. Measured with infrequent test pulses, 0.123 mM lidocaine reduced INa to 54%, 0.25 mM benzocaine to 40% and the mixture 0.125 mM lidocaine +/- 0.25 mM benzocaine to 31% of the control. When hyperpolarizing prepulses (V = -40 mV for 15 ms) preceded the test pulses the respective reductions were to 58%, 74% and 55% i.e. adding benzocaine to lidocaine had little additional effect. 3. Increasing the rate of the prepulse test pulse pairs from 1 to 20 Hz did not change INa in benzocaine but gradually relieved block by lidocaine; in the mixture this change was much reduced or absent. 4. Switching off prepulses (at 20 Hz) led to a gradual decrease of INa in lidocaine but to a prompt fall in benzocaine and in the mixture. 5. 0.25 mM lidocaine and 0.5 mM benzocaine were approximately equieffective in reducing INa (no prepulse) to 29% and 24%; a one-to-one mixture of the two solutions (0.125 mM lidocaine + 0.25 mM benzocaine) reduced to 27%. 6. In current clamp experiments 0.25 mM lidocaine and 0.36 mM benzocaine reduced the maximum rate of rise of the action potential to 32% and 30%, the mixture of solutions (0.125 mM lidocaine + 0.18 mM benzocaine) to 29%. 7. These results are fully compatible with the idea of a single common binding site for which lidocaine and benzocaine compete. PMID- 6251427 TI - A new extraction of arginine vasopressin from blood: the use of octadecasilyl silica. AB - Small columns packed with octadecasilyl-silica were used to extract arginine vasopressin in femtomole amounts from biological fluids for radioimmunoassay. This method is effective in isolating the peptide from substances in plasma and serum which interfere with its quantitation. Consistent and reproducible results and recoveries > 80% were obtained with this procedure. High pressure liquid chromatography and serial dilution of extracted samples confirm the identity of the extracted product. PMID- 6251429 TI - [Quantitative whole-body bone scintigraphy. I. Methodology (author's transl)]. AB - Quantitative whole-body bone scintigraphy is a method for evaluating digital bone scans. Its principles are: use of a double detector scanner and correction of attenuation and organ thickness effects in the scan; its results: calculation of whole-body activity, relation of bone, soft tissue and organ activity, distribution of the activity in single regions of the skeleton expressed as a percentage. The mean error of the results of 10%. By comparison with a standardized normal scan a local concentration factor for focal and diffuse bone alterations expressing quantitatively increased bone metabolism. The calculation is made automatically by computer. Further papers will report on the application of the method to the evaluation of the kinetics of bone seekers and on clinical experiences. PMID- 6251428 TI - Differences between K channels in motor and sensory nerve fibres of the frog as revealed by fluctuation analysis. AB - Differences between K channels in the nodal membrane of sensory and motor myelinated nerve fibres of the frog were investigated by fluctuation analysis. Spectral densities, S(f), between 3 Hz and 5 kHz were determined from K-current fluctuations measured between 145 and 460 ms after the onset of depolarizations V between 16 and 80 mV. Fits by the sum of a 1/f component and Lorentzian spectra corresponding to Hodgkin-Huxley n4-kinetics gave significant deviations from the measured spectra. The best fit was obtained by: S(f) = S1/[1+(f/fc)1.5]+S2. The first term can be interpreted as a diffusion spectrum which would originate from gating of K channels governed by an electrodiffusion process. To describe the spectral density at frequencies above 1 kHz it was necessary to add the plateau S2. Time constants taun* = 1/(2pifc) are roughly equal to the conventional Hodgkin-Huxley time constant taun only for pulses V < 40mV. At higher depolarizations taun increases with increasing depolarization in contrast to taun. The variance, var, of conductance fluctuations was determined by integration of the first component of S(f). From var, the probability of the open channel state, and the steady-state K current the single-channel conductance gamma and the number N of K channels per node were calculated; all parameters were corrected for K accumulation during depolarizing pulses. gamma and N were found to be only weakly voltage-dependent. The mean values over all voltages are for motor fibres: gamma=2.7 pS, N = 5.7 x 10(4), and for sensory fibres: gamma = 4.6 pS, N = 5.2 x 10(4). The results suggest two different kinds of K channels in motor and sensory nerve fibres. PMID- 6251430 TI - [Functional imaging of characteristic kinetic parameters of kidney and thyroid (author's transl)]. AB - A procedure has been developed by which the reaction of an organ to a very short delta-function activity pulse of an organ-specific tracer introduced into the blood can be determined for the kidney and the thyroid. The data for the procedure are available from sequence scintigrams and the change with time of the activity of the tracer in the blood. The nature and duration of this reponse function makes it possible to calculate organ-specific parameters such as uptake rates, clearance rates or transit times. They may be calculated for the total field of the gamma camera and delineated as grey or colour gradations to yield the respective parametric functional images. The apparatus necessary for the procedure is described and its possible clinical application in comparison to conventional scintigraphic procedure is discussed. PMID- 6251431 TI - A hospital-based home care program. PMID- 6251432 TI - The significance and impact of the home care of an older adult. PMID- 6251433 TI - [Role of nutrition in the development of neoplasms]. PMID- 6251434 TI - [Activity of various lysosomal enzymes in the peripheral blood leukocytes in hyperthyroidism]. PMID- 6251435 TI - [Insulin secreting islet cell tumor - diagnostic problems]. PMID- 6251436 TI - Enzyme-histochemical differentiation of neuroglia and microglia: a contribution to the cytogenesis of microglia and globoid cells. Review of the literature. PMID- 6251437 TI - The application of glial fibrillary acidic (GFA) protein immunohistochemistry in neurooncology. A progress report. PMID- 6251439 TI - Localization of herpesvirus of turkeys in blood cells. AB - The buffy coat pellets of blood clots from Broad Breasted Large White turkeys were processed for electron microscopy. No viruses were found in extracellular spaces nor in the heterophils, eosinophils, or basophils. Enveloped virions, measuring approximately 135 nm in diameter consisting of a core 30 to 35 nm in diameter and a capsid 20 to 30 nm thick were found in cytoplasmic vacuoles in lymphocytes. No developmental stages of virus maturation were observed in the nuclei or cytoplasm of any of the lymphocytes. Virus-like particles were observed in the nuclei and perinuclear zones of many erythrocytes and were approximately 135 nm in diameter but did not possess herpesvirus morphology. PMID- 6251438 TI - Mucinous adenocarcinoma of the renal pelvis. AB - A case of mucinous adenocarcinoma of the renal pelvis occurring in association with staghorn calculus and severe pyelonephritis is reported. The incidence and aetiopathogenesis of this neoplasm is briefly discussed. PMID- 6251440 TI - Divergent selection in Japanese quail for the plasma cholesterol response to ACTH. AB - Two lines of Japanese quail were divergently selected for high and low plasma cholesterol levels after three daily injections with 2 IU of adrenocorticotropen (ACTH)/100 g of body weight. Plasma cholesterols were obtained at 31 days of age, just before the first injection, and at 34 days of age, after the last injection. After eight generations of selection, the plasma cholesterol level after ACTH injections in the high line was 34% greater than the level in the control line, whereas the low line level was approximately 14% less than that in the control. Selection differentials were significantly greater in the high line than in the low line. The realized heritability for plasma cholesterol before ACTH treatment calculated by regression of progeny on mid-parent was .25 in the high line and .16 in the low line. PMID- 6251441 TI - Effect of adrenocorticotropin on binding of endogeneous corticosteroid by chicken bursal cells. AB - An intravenous injection of ACTH stimulated a maximal increase in the serum concentration of corticosterone within 60 to 65 min. This increase was closely paralleled by the amount of corticosterone which was bound to be cytoplasmic and nuclear fractions of chicken bursal cells. PMID- 6251442 TI - Ubiquity of infectious bursal disease in East Texas backyard flocks. AB - Sera from 25 "backyard" flocks were screened by agar-gel precipitin (AGP) and virus-neutralization (VN) tests for antibodies to infectious bursal disease virus. Although titers varied from flock to flock, 100% of the birds screened had virus-neutralizing antibodies. In general, birds with high VN titers had positive AGP reaction. PMID- 6251443 TI - Purification of subcomponents Clq, Cl(-)r and Cl(-)s of the first component of complement from Cohn Fraction I by affinity chromatography. PMID- 6251444 TI - [Electroroentgenoscanning in the diagnosis of expanding mediastinal growths]. AB - Thirty eight patients with the upper mediastinal tumours were examined by electroroentgenoscanning; 35 of these were operated on later and the diagnosis was confirmed. Comparison of the thyroid gland scannogram with the chest roentgenogram aided recognition of the nature of the detected formation. In cases of nonfunctional stromas the results of this method should be considered only in combination with other data. PMID- 6251445 TI - [Effect of ACTH in the biosynthesis of prostaglandins, adenosine cyclic monophosphate and steroids in the adrenal cortex of rabbits in vivo]. AB - The effect produced by intravenous injection of ACTH to rabbits on the content of prostaglandins E and F (PGE and PGF) in the adrenal glands was studied. At the same time a determination was made of the cAMP content in the adrenal glands and of the peripheral blood corticosterone concentration. PGE and PGF were revealed in the adrenal cortex in concentrations of 199--550 and 271--335 pg/g respectively. After a dose of 50 Units there was a 2--3-fold rise of PGE, and a 1 1/2-fold rise of the PGF content. PG synthesis was elevated maximally in the adrenal glands 15 minutes after the ACTH injection, remaining at this level for 60 minutes; similar dynamics was revealed for the cAMP and corticoterone formation. The results obtained indicated that, along with intensification of the steroids and cAMP formation, ACTH stimulated PG synthesis in the adrenal glands. These data permit a suggestion to be made that PG participated in the ACTH action on the adrenal glands. PMID- 6251446 TI - [Role of the anterior pituitary gland in the regulation of 18 hydroxydesoxycorticosterone by the adrenal cortex]. AB - The work is devoted to a study of the hypophysis control of the adrenal cortex hormone--18-hydroxy-11-deoxycorticosterone (18-HO-DOC) secretion; these investigations were performed on 136 mongrel female rats, weighing 130-140 g. The regulating role of the hypophysis on the 18-HO-DOC secretion was ascertained on the hypophysectomized animals (pseudohypophysectomized animals served as control) and intact rats to which ACTH was administered (physiological saline was injected to control animals). The rate of secretion, specific rate of secretion, and the secretion content in the blood and in the arenal efferent and the peripheral vessels were determined by thin-layer chromatography and competitive protein binding. The data obtained led to the conclusion that both corticosterone and 18 HO-DOC were regulated by the hypophysis. Under the effect of stress there apparently occurred selective regulating action of ACTH on 18-HO-DOC and corticosterone secretion indicating that the expediency of elevation of one or another steroid secretion was determined by the character of stress reaction, the blood adrenocorticotropin and corticosteroid level. PMID- 6251447 TI - Synthesis, cloning, and identification of DNA sequences complementary to mRNAs for alpha and beta subunits of thyrotropin. AB - Double-stranded cDNA sequences were synthesized, by using as templates mRNA for alpha and beta subunits of thyrotropin purified from mouse thyrotrophic pituitary tumours and cloned in Escherichia coli RR1 by insertion in the Pst I site of the bacterial plasmid pBR322 by use of poly(dA) x poly(dT) homopolymeric extensions. Plasmids containing inserted cDNA sequences were selected by resistance to tetracycline and sensitivity to ampicillin; those containing thyrotropin cDNA sequences were identified by colony hybridization with an 125I-labeled mixture of alpha and beta thyrotropin mRNAs. Plasmids carrying either alpha or beta thyrotropin cDNA sequences were further identified by hybridization to highly purified 125I-labeled alpha or beta thyrotropin mRNA, respectively. Two plasmids, one containing a 400-nucleotide alpha thyrotropin cDNA insert and the other containing a 710-nucleotide beta thyrotropin cDNA insert, were purified and characterized by restriction endonuclease digestions. Plasmid [32P]DNA containing either alpha or beta thyrotropin cDNA was then used as a hybridization probe for further characterization of alpha and beta thyrotropin mRNA from the mouse thyrotropic tumor. RNA was fractionated by agarose gel electrophoresis under denaturing and nondenaturing conditions and transferred to diazobenzyloxymethyl paper. alpha thyrotropin mRNA of two sizes, 650 and approximately equal to 1500 nucleotides long, were identified. The larger alpha thyrotropin mRNA appeared to have marked secondary structure in its native form in contrast to the 650 nucleotide alpha thyrotropin mRNA. However, only one form of beta thyrotropin mRNA was detected with an apparent size of 710 nucleotides. We have successfully cloned and identified alpha and beta thyrotropin cDNA sequences in bacterial plasmids and used them to identify a second form of alpha thyrotropin mRNA. PMID- 6251448 TI - Structure and phosphorylation of microtubule-associated protein 2 (MAP 2). AB - Chymotryptic fragments of microtubule-associated protein 2 (MAP 2) containing the portion of the molecule responsible for promoting microtubule assembly were identified. These assembly-promoting fragments displaced intact MAP 2, but not MAP 1, from assembled microtubules. This indicates that the association of MAP 2 with the microtubule surface is reversible. Both the assembly-promoting fragments and fragments representing the portion of the MAP 2 molecule observed as a projection on the microtubule surface were found to contain sites for endogenous cyclic AMP-dependent phosphorylation. The projection fragments were capable of endogenous phosphorylation even after their physical separation from microtubules. This suggests an intimate association of a kinase activity with the projections. Detailed analysis of the properties of the chymotryptic fragments of MAP 2 has led to a map of the molecule showing the major sites of proteolytic attack and the sites of phosphorylation. PMID- 6251449 TI - beta-Endorphin omission analogs: dissociation of immunoreactivity from other biological activities. AB - An analog of human beta-endorphine with omission of four residues at positions 11, 14, 20, and 22 has been synthesized. This analog and other synthetic analogs with deletion of a single amino acid at position 2, 5, 6, 10, 11, 12, 13, 15, or 22 have been assayed for analgesic potency, ileal opiate activity,opiate receptor binding activity, andimmunoreactivity. Results show that deletion of a single amino acid of the beta-endorphin molecule outside of the enkephalin segment to give des-Gln11-, des-Thr12, des-Pro13-, des-Leu14-, des-Val15-, des-Asn20-, or des-Ile22-beta-endorphin markedly reduced or abolished the immunoreactivity yet gave substantial retention of opiate potencies. Deletion of a single amino acid of beta-endorphin within the enkephalin segment (des-Gly3- or des-Met5-beta endorphin) did not markedly affect the immunoactivity; however, the opiate activities were abolished or markedly reduced. The data indicate a clear dissociation of immunoactivity from analgesic, ileal-opiate, and opiate receptor binding activities. PMID- 6251450 TI - Integrative recombination of bacteriophage lambda: extent of the DNA sequence involved in attachment site function. AB - We have investigated the minimum extent of DNA sequence required for the attachment site of bacteriophage lambda to function in integrative recombination. A DNA fragment carrying the phage attachment site (attP) of bacteriophage lambda was trimmed, recloned, and tested for recombination proficiency. In order to recombine with the bacterial attachment site (attB), the phage attachment site must retain about 250 base pairs of its original sequence. On the left side, the essential sequence extends beyond 106 base pairs from the center of the 15-base pair common core sequence but not beyond 152 base pairs. On the right side the required sequence extends beyond 68 base pairs but not beyond 99 base pairs from the center of the core. A trimmed site that has lost part of the sequence mentioned above cannot function as the phage attachment site. However, depending on which part of the sequence is present, such a site can still act in reactions normally requiring one of the prophage attachment sites or the bacterial attachment site. The results also suggest that the essential suquence of the bacterial attachment site consists only of the sequence common to the phage and bacterial attachment sites. PMID- 6251451 TI - Coding capacity of a 35 percent fragment of the polyoma virus genome is sufficient to initiate and maintain cellular transformation. AB - Rat-1 cells were transfected with the restriction enzyme fragment of polyoma virus DNA that extends clockwise from the Bcl I site ((65.4 map units) to the EcoRI site (0/100 map units). Six transformed cell lines were obtained and one of them (BE-1) has been investigated in detail. The viral DNA that is integrated into host DNA in this line appeared to consist of two fragments arranged in a "head-to-tail" tandem with no detectable intervening host sequences. BE-1 cells contained polyoma virus small and middle tumor antigens that were indistinguishable from the corresponding tumor antigens from lytically infected cells. No large tumor antigen was detected but a "new" Mr 34,000 protein, which proved to be a truncated version of large tumor antigen, was immunoprecipitated by anti-tumor-antigen antiserum. After injection of 10(6) BE-1 cells into young syngeneic Fischer rats, tumors appeared within 3--4 weeks. Thus, the coding capacity of the Bcl I/EcoRI fragment of polyoma virus DNA is sufficient to enable the cells to produce all of small and middle tumor antigens and about a third of large tumor antigen, to transform cells stably in culture, and to produce tumors in vivo. PMID- 6251452 TI - Lysomotropic amines cause intracellular accumulation of receptors for epidermal growth factor. AB - By direct biochemical methods, we demonstrate that the process of internalization of receptors for epidermal growth factor (EGF) occurs even without EGF stimulation and is not prevented by the lysomotopic agents methylamine or chloroquine. These agents inhibit the degradation of 125I-labeled EGF, thus preventing the rapid dissociation of EGF from cells. Furthermore, 125I-labeled EGF incubated with cells in the presence of methylamine becomes increasingly insensitive to trypsin with time, suggesting that the EGF receptor internalization is not prevented by alkylamines, but that there is an intracellular accumulation of ligand--receptor complex due to the loss of normal modes of ligand-induced receptor processing. Lysis of cells treated with methylamine results in recovery of 125I-labeled EGF binding. Fractionation of these lysates on sucrose density gradients demonstrates that EGF receptors are localized within membrane fractions having higher densities than fractions from lysates of untreated cells. PMID- 6251453 TI - 5,6-dichloro-1-beta-ribofuranosylbenzimidazole enhances premature termination of late transcription of simian virus 40 DNA. AB - Short RNA chains initiating at the major promoter sites for simian virus 40 (SV40) late transcription are elongated to approximately 450 nucleotides in a molar ammount greater than that from any other region of the viral DNA. This conclusion is based on the following observations: (i) Transcriptional complexes isolated by Sarkosyl and by hypotonic leaching (minichromosomes) from nuclei of cells infected with SV40 as well as intact nuclei were pulse labeled in vitro with [alpha-32P]TUP and were observed to synthesize short RNA transcripts that hybridized predominantly to a SV40 DNA fragment spanning between 0.67 and 0.76 map units. (ii) In the presence of 5,6-dichloro-1-beta-D ribofuranosylbenzimidazole (DRB), a drug known to accentuate premature transcriptional termination, accumulation of these short SV40 RNA chains was enhanced. When SV40-infected cells were pretreated with DRB and then labeled in vivo or in vitro, they synthesized short labeled viral RNAs that hydridized almost exclusively with the DNA fragment spanning between 0.67 and 0.76 map units. These observations suggest a mechanism in the regulation of SV40 late transcription. PMID- 6251454 TI - Nucleotide sequence of Moloney leukemia virus: 3' end reveals details of replications, analogy to bacterial transposons, and an unexpected gene. AB - We have determined the sequence of a cloned DNA fragment 1108 base pairs long which corresponds to the 3' end of the Moloney murine leukemia provirus. The clone was obtained as the primary product of reverse transcription and begins with the Moloney "strong stop" sequence, then extends towards the 5' end of the provirus. Our sequence: (i) proves that reverse transcriptase switches templates during minus strand synthesis; (ii) defines the limits of the 515-base-pair repeats which occupy both ends of the integrated provirus; (iii) shows that the structure of the proviral repeats has strong analogy to bacterial insertion sequences, indicating that the Moloney provirus is a transposon; (iv) identifies the putative promotor for genomic transcription within these repeats; (v) shows that the presumed origin of second strand synthesis, which lies just outside the 3' repeat, has tertiary structure analogous to single-stranded bacteriophage origins of replication; (vi) solves the amino acid sequence of most of pI5E, the carboxy-terminal product of the env gene; (vii) allows detailed mapping of the mink cell focus-forming virus substitution locus in a central location within the gp70 region of the env gene; and (viii) identifies a long open translation frame to the right of the env gene (R gene) which could be involved in leukemogenesis. PMID- 6251455 TI - Structure of Moloney murine leukemia viral DNA: nucleotide sequence of the 5' long terminal repeat and adjacent cellular sequences. AB - Some unintegrated and all integrated forms of murine leukemia viral DNA contain long terminal repeats (LTRs). The entire nucleotide sequence of the LTR and adjacent cellular sequences at the 5' end of a cloned integrated proviral DNA obtained from BALB/Mo mouse has been determined. It was compared to the nucleotide sequence of the LTR at the 3' end. The results indicate: (i) a direct 517-nucleotide repeat at the 5' and 3' termini; (ii) 145 nucleotides out of 517 nucleotides represent sequences between the 5'-CAP nucleotide and 3' end of the primer tRNA (strong-stop DNA); (iii) an 11-nucleotide inverted repeat is present at the ends of the 5'-LTR and a total of 17 out of 21 nucleotides at the termini are inverted repeats; (iv) sequences CAATAAAAG (at positions -24 to -31) and CAATAAAC (at positions +46 to +53) resembling the hypothetical DNA-dependent RNA polymerase II promoter site can be identified in the 5'-LTR; (v) the sequence GAAA appears to be repeated on both sides of the junction of viral and cellular sequences; and (vi) in analogy with the bacterial transposons, the presence of an inverted repeat sequence at the termini of 5'-LTR suggests that M-MLV also has the integration properties of a transposon. PMID- 6251456 TI - Multienzyme complex for metabolic channeling in mammalian DNA replication. AB - In the DNA-synthesizing phase (S phase) of CHEF/18 Chinese hamster embryo fibroblast cells, six enzymes associated with DNA metabolism, including DNA polymerase (deoxynucleoside triphosphate:DNA deoxynucleotidyl-transferase, EC 2.7.7.7), were largely localized in the nuclear region (karyoplasts). By contrast, in quiescent and G1 phase cells these enzymatic activites were mainly absent from the nucleus and were recovered in the cytoplasmic portion (cytoplasts). These nuclear (but not cytoplasmic) enzymatic activities cosedimented rapidly on sucrose density gradients. Further, the rapidly sedimenting enzyme activities were unique to cells in S phase. An organized supramolecular structure that allows channeling of metabolites into DNA was demonstrated by kinetics of nucleotide incorporation. "Permeabilized" cells selectively channeled incorporation of ribonucleoside diphosphates into DNA in preference to deoxyribonucleoside triphosphates. Deoxyribonucleoside triphosphate incorporation occurred when ribonucleoside-diphosphate reductase (2' deoxyribonucleoside-diphosphate: oxidized-thioredoxin 2'-oxidoreductase, EC 1.17.4.1) activity was abolished by hydroxyurea. Our interpretation is that during DNA replication, the nucleus contains a complex of DNA precursor synthesizing enzymes juxtaposed with the "replication apparatus" comprising DNA polymerase, other enzymes, and structural proteins. Functional integrity of this structure is impaired when one of its essential components is inactivated. We propose the name "replitase" for this multienzyme complex for DNA replication and suggest that it incorporates precursors rapidly and efficiently. Possibly its assembly signals the initiation of the S phase of the cell cycle. PMID- 6251457 TI - The Escherichia coli L-arabinose operon: binding sites of the regulatory proteins and a mechanism of positive and negative regulation. AB - The locations of DNA binding by the proteins involved with positive and negative regulation of transcription initiation of the L-arabinose operon in Escherichia coli have been determined by the DNase I protection method. Two cyclic AMP receptor protein sites were found, at positions -78 to -107 and -121 to -146, an araC protein--arabinose binding site was found at position -40 to -78, and an araC protein-fucose binding site was found at position -106 to -144. These locations, combined with in vivo data on induction of the two divergently oriented arabinose promoters, suggest the following regulatory mechanism: induction of the araBAD operon occurs when cyclic AMP receptor protein, araC protein, and RNA polymerase are all present and able to bind to DNA. Negative regulation is accomplished by the repressing form of araC protein binding to a site in the regulatory region such that it stimultaneously blocks access of cyclic AMP receptor protein to two sites on the DNA, one site of which serves each of the two promoters. Thus, from a single operator site, the negative regulator represses the two outwardly oriented ara promoters. This regulatory mechanism explains the known positive and negative regulatory properties of the ara promoters. PMID- 6251458 TI - Eukaryotic signal sequence transports insulin antigen in Escherichia coli. AB - We made a series of plasmids with unique Pst restriction sites within or near the DNA that encodes the penicillinase signal sequence. Inserted DNA can be read in all three frames both within and immediately after the signal sequence. We cloned Pst-terminated DNA copies of the structural information for rat proinsulin and preproinsulin into these plasmids, forming a large number of hybrid penicillinase (bacterial) and insulin (eukaryotic) signal sequences. We then compared the levels of insulin antigen in the Escherichia coli periplasm with those inside the cells. We conclude that either the bacterial or the eukaryotic signal is sufficient to transport rat insulin antigen into the periplasmic space. PMID- 6251459 TI - Aggregation of luteinizing hormone receptors in granulosa cells: a possible mechanism of desensitization to the hormone. AB - The temporal relationship between redistribution of receptors to lutropin (luteinizing hormone)/human chorionic gonadotropin in cultured rat ovarian granulosa cells and the cellular response to hormonal challenge were studied. Visualization of receptor-bound human chorionic gonadotropin by indirect immunofluorescence, with hormone-specific antibodies after fixation with 2% formaldehyde, revealed the existence of small clusters around the entire cell circumference 5--20 min after exposure to the hormone at 37 degrees C. Such small receptor aggregates were also evident if hormone incubation was at 4 degrees C or if cells were fixed with 2% formaldehyde before incubation. Larger clusters were evident after prolonged incubation with the hormone (2--4 hr) at 37 degrees C. The later change coincided with diminished cyclic AMP accumulation in respose to challenge with fresh hormone. When the fixation step was omitted and antibodies to human chorionic gonadotropin were applied after hormonal binding, acceleration of both receptor clustering and the desensitization process was observed. This maneuver also induced capping of the hormone receptors. In contrast, monovalent Fab' fragments of the antibodies were without effect. Internalization of the bound hormone in lysosomes, and subsequent degradation, was evident 8 hr after hormonal application and was not accelerated by the antibodies. It is suggested that clustering of the luteinizing hormone receptors may play a role in cellular responsiveness to the hormone. Massive aggregation of the receptors may desensitize the cell by interferring with coupling to adenylate cyclase. PMID- 6251460 TI - Toward a model for the molecular genetics of carcinogenesis in rats. AB - Cultured rat embryo cells are resistant to neoplastic transformation by chemical carcinogens unless they are extensively subcultured or infected with a murine leukemia virus (MuLV) first. We found that, in normal cultured cells, MuLV activates expression of rat genes that are the progenitors of sarcoma virus genes, but not those of endogenous "leukemia" virus. Elevated levels of sarcoma virus-related RNA in normal cells infected with MuLV were indistinguishable from the levels in cells transformed spontaneously or by a carcinogen or a sarcoma virus. Because of previous reports that some carcinomas in rats also contain elevated levels of sarcoma virus-related RNA, we believe these events can be explained by a molecular genetic model which may be generally valid for initiation of carcinogenesis. The basic elements of the model are: transcriptional activation of all the multiple copies of normal rat progenitors of sarcoma virus genes is required before cellular transformation can be initiated, and initiation occurs when a spontaneous or induced mutation in any one active copy of these same genes generates a dominant transforming function. PMID- 6251461 TI - Association of the src gene product of Rous sarcoma virus with cytoskeletal structures of chicken embryo fibroblasts. AB - We have prepared cytoskeletons from normal and Rous sarcoma virus-transformed cells by extraction with nonionic detergents in a buffered salt solution designed to preserve the structure as it exists in vivo. Virtually all of the phosphoprotein pp60src in the cell is bound to such cytoskeletons. Furthermore, when these cytoskeletons are incubated in situ with [gamma-32P]ATP, pp60src is phosphorylated. Labeling of other apparently transformation-specific cytoskeletons phosphoproteins is also observed. These results directly demonstrate an association between pp60src and elements of the cytoskeleton and suggest that pp60src may exert at least some of its effects as a consequence of its interaction with this cellular framework. PMID- 6251462 TI - Transforming growth factors: isolation of polypeptides from virally and chemically transformed cells by acid/ethanol extraction. AB - Polypeptides characterized by their ability to confer a transformed phenotype on an untransformed indicator cell have been isolated directly from tumor cells growing both in culture and in the animal, by using an acid/ethanol extraction procedure. Assay of these polypeptides is based on their ability to induce normal rat kidney fibroblasts to form colonies in soft agar. Peptides from murine sarcoma virus-transformed mouse 3T3 cells grown in culture had the highest specific activity in this assay; peptides from sarcomas produced from these cells or from chemically induced transplantable bladder carcinomas of mice were one third as active; and peptides from a chemically induced rat tracheal carcinoma had only one-tenth the activity. Treatment with either trypsin or dithiothreitol destroyed the activity of all of these materials. The properties of these intracellular polypeptides from both virally and chemically transformed cells are similar to those described for the sarcoma growth factors (SGFs) previously isolated from the conditioned medium of sarcoma virus-transformed mouse 3T3 cells, suggesting the definition of a class of transforming growth factors common to tumor cells of different origins. The transforming peptides from the cultured sarcoma virus-infected cells were separately by gel filtration into two fractions of apparent molecular weight 7000 and 10,000. The major fraction at molecular weight 7000 represented approximately 0.1% of the original cell protein and had a specific activity 50 times that of the original acid/ethanol extract. PMID- 6251463 TI - Biological activity of cloned Moloney sarcoma virus DNA: Terminally redundant sequences may enhance transformation efficiency. AB - We have measured the ability of cloned restriction fragments containing the whole and partial genomes of two strains of Moloney murine sarcoma virus to induce cell transformation in DNA transfection assays. The cloned intact ml and HTl murine sarcoma virus proviruses transform with an efficiency of approximately 40,000 50,000 focus-forming units/pmol of proviral DNA, and the majority of these transformed cells contain a rescuable viral genome. A cloned 2.1-kilobase-pair internal fragment of the murine sarcoma virus containing 1.2 kilobase pairs of sarcoma virus-specific sequences (src) and approximately 900 base pairs of leukemia virus-derived sequences adjacent to the 5' end of src transforms with approximately 1/10,000th the efficiency of the intact genome. When leukemia virus deprived sequences containing a single copy of the 600-base-pair direct terminal repeated sequences are present at either the 5' or 3' end of this src-containing fragment, the transforming activity is stimulated 1000-fold. Cotransfection with a mixture of cloned fragments, one containing the internal 2.1-kilobase-pair src fragment and the other containing a single copy of the terminally redundant sequence, results in a 300-fold increase in transformation efficiency. PMID- 6251464 TI - Adhesion plaques of Rous sarcoma virus-transformed cells contain the src gene product. AB - Another intracellular location of the Rous sarcoma virus (RSU) src gene product (pp60src) has been detected within RSV-transformed cells by indirect immunofluorescence. By using rabbit anti-tumor serum specific for pp60src, a speckled pattern of fluorescence was found on the ventral surface of RSV (Schmidt Ruppin strain)-transformed normal rat kidney cells. Several tests indicated that this pattern was specific for pp60src. In addition, interference-reflection microscopy was used to visualize cellular adhesion plaques, which are the points at which cells attach to the substratum. Simultaneous immunofluorescence and interference-reflection microscopy indicated that the speckles of pp60src fluorescence corresponded exactly to the adhesion plaque structures. The presence of pp60src within the adhsion plaques was further demonstrated by indirect immunofluorescences on isolated adhesion plaques that remained bound to glass after removal of the cells. pp60src also was observed in adhesion plaques of RSV tranformed chicken embryo fibroblasts (CEF) and mouse fibroblasts, as well as CEF infected with the temperature-sensitive RSV mutant tsNY68 and grown at permissive temperature. At nonpermissive temperature, pp60src was not detectable in adhesion plaques of the tsNY68-infected CEF. Adhesion plaques serve as focal points of microfilament bundle attachment, and thse results suggest that pp60src interacts directly with cellular cytoskeletal components. PMID- 6251465 TI - Transformation of Streptococcus pneumoniae with S. pneumoniae-lambda phage hybrid DNA: induction of deletions. AB - The genetic fate of a fragment of Streptococcus pneumoniae DNA cloned into a derivative of the Escherichia coli bacteriphage lambda has been studied in pneumococcal transformation. Transforming activity of this hybrid DNA is 8 times higher than standard S. pneumoniae DNA. Hybrid DNA is mutagenic for the recipient bacteria. Mutations are induced at a rate of 2 per 1000 transformation events. Most of these mutations are deletions adjacent to the cloned pneumococcal fragment, starting at or near its extremities and extending outside. The length of these deletions, estimated by genetic analysis or by gel electrophoresis of DNA fragments generated by restriction endonucleases, is quite variable, ranging from 150 base pairs to more than 1800 base pairs. Insertion of lambda DNA bas been detected in two large deletions by using DNAxDNA hybridization as a probe. This suggests that nonhomologous regions adjacent to the cloned fragment may be illegitimately integrated by the tranformation process. During the genetic analysis of these induced mutations we have observed that not only these deletions but also spontaneous deletions drastically increase recombination rates when present on donor DNA in transformation of neighboring markers. Such an effect is interpreted as partial exclusion of deletions from synapsis between donor and recipient DNA. PMID- 6251466 TI - Cloning and direct examination of a structurally abnormal human beta 0 thalassemia globin gene. AB - Restriction endonuclease mapping permitted identification of a form of beta 0 thalassemia in which a partial deletion of the beta-globin structural gene occurred [Orkin, S. H., Old, J. M., Weatherall, D. J. & Nathan, D. G. (1979) Proc. Natil. Acad. Sci. USA 76, 2400-2404]. To analyze its structure more directly, this abnormal human gene has now been cloned in bacteriophage lambda gtWES. Restriction mapping of the cloned gene and of a normal beta-globin gene contained in the phage H beta G1 confirmed previous findings regarding the presence of a deletion toward the 3' end of the gene but could not establish its position more accurately. Electron microscopy of the hybrid of the beta thalassemia gene with globin RNA (R-loop analysis) provided unequivocal evidence for a deletion with the beta-globin structural gene. Hybridization of restriction fragments of the mutant gene with homologous fragments of H beta G1 (heteroduplex analysis) revealed a continuous, internal deletion of about 0.6 kilobase of DNA in the mutant gene and permitted its localization within the beta-globin gene region. This deletion removed the terminal third of the large intervening sequence within the beta-globin gene, the entire 3' coding block (extending from codon 105 to the end of the gene), and approximately 150 base pairs of DNA past the end of the normal globin gene. PMID- 6251467 TI - Silent delta-globin gene in Old World monkeys. AB - The delta polypeptide chain is present in the adult hemoglobin of all higher primates except Old World monkeys. Because Old World monkeys have evolved from higher primate ancestors, it can be concluded that the ability to synthesize this polypeptide has been lost relatively recently. It is shown here that the gene for delta globin exists in two of these species, the rhesus monkey (Macaca mulatta) and the baboon (Papio papio). Restriction endonuclease fragments of monkey genomic DNA bearing the delta- and beta-globin genes were detected after hybridization of human globin cDNA probes to filter-bound primate DNAs according to the Southern method. A restriction map prepared for rhesus DNA was identical in overall organization to the map of the human region. This indicates that large deletions or additions of DNA are not responsible for the Old World monkeys' lack of delta globin. PMID- 6251468 TI - Transformation of mammalian cells with an amplifiable dominant-acting gene. AB - We have transferred a mutant hamster gene coding for an altered dihydrofolate reductase to wild-type cultured mouse cells by using total genomic DNA from methotrexate-resistant Chinese hamster ovary A29 cells as donor. By demonstrating the presence of hamster gene sequences in transformants we have provided direct evidence for gene transfer. Transformants selected for increased resistance to methotrexate contain increased amounts of the newly transferred gene. We have used this mutant dhfr gene to introduce the Escherichia coli antibiotic resistance plasmid pBR322 into animal cells. Amplification of the dhfr sequences results in amplification of the pBR322 sequences as well. The use of this gene may allow the introduction and amplification of virtually any genetic element in various new cellular environments. PMID- 6251469 TI - Intracisternal A-particle genes: identification in the genome of Mus musculus and comparison of multiple isolates from a mouse gene library. AB - The genome of Mus musculus contains multiple copies (500 -1000) of DNA sequences related to the 35S RNA of intracisternal type A particles (IAPs). Using labeled IAP RNA as a probe in blot-hybridization experiments, we have identified a characteristic electrophoretic pattern of reactive fragments generated by restriction endonuclease cleavage of mouse DNA. From the genomic blots, we deduced a composite restriction map for a 6.5- to 7-kilobase (kb) DNA region containing sequences homologous to the IAP RNA. Units of this type appeared to be interspersed without obvious regularity in nonhomologous flanking regions. A 5.2 kb segment of this unit was inserted directly into plasmid pBR322 from HindIII/EcoRI digest of mouse DNA. The fragment was cloned and then labeled by nick-translation and used to scan a mouse embryo gene library (average 16-kb inserts in lambda Charon 4A); 1% of the library samples hybridized, confirming the extensive reiteration of IAP genetic units. Among six different library isolates containing 6.5- to 7-kb IAP units, some restriction sites were highly conserved whereas others varied in both occurrence and position. Despite this variation, heteroduplexes between the individual isolates showed continuous IAP homology regions of 7 kb. No flanking region homologies were seen in this limited sample. Some evidence suggests that mouse DNA may contain other dispersed sequence elements related to but smaller than the genetic unit defined above. PMID- 6251470 TI - Identification of 5-methylcytosine in DNA fragments immobilized on nitrocellulose paper. AB - A method to identify 5-methylcytosine (m5Cyt) in DNA immobilized on nitrocellulose paper by using antibody against m5Cyt raised in rabbits is described. Immobilized restriction fragments of DNA are incubated first with purified antibody against m5Cyt and then with goat anti-rabbit IgG labeled with 125I. Restriction fragments containing m5Cyt are visualized by autoradiography. By using this method, a heavily methylated fragment of about 1700 base pairs was identified in nuclear DNA fom Chinese hamster cells, the methylation pattern of calf thymus satellite I DNA was examined, and chloroplast DNAs that were extracted from various stage of the Chlamydomonas life cycle were compared. Little if any methylation was detected in chloroplast DNA from vegetative cells or from male gametes, whereas homologous DNAs from female gametes and from zygotes were heavily methylated. The sensitivity of the method was examined with calf thymus satellite I DNA (which contains approximately 40 m5Cyt residues per repeat unit of 1400 base pairs) and with phi X174 virion DNA (which contains a single m5Cyt per molecule). The presence of m5Cyt was detected with as little as 40 ng of phi X174 DNA containing 0.02 pmol of m5Cyt and with 100 ng of satellite DNA containing about 0.5 pmol of m5Cyt. Thus, the method makes possible the identification of individual methylated sites in purified DNAs in the size range of single genes. PMID- 6251471 TI - Feedback regulation of ribosomal protein gene expression in Escherichia coli. AB - The structural genes for Escherichia coli ribosomal protein (r-protein) genes L1, S4, and S11 were inserted into a plasmid vector containing the lac operator and promoter such that the synthesis of L1, S4, and S11 was controlled by lac regulatory elements. Synthesis of L1, S4, and S11 was stimulated by addition of an inducer of the lac operon (isopropyl thiogalactoside) to exponentially growing cells. Elevated synthesis of L1 caused a specific decrease in L11 synthesis, whereas overproduction of S4 resulted in lowered synthesis of S13 and L17. Stimulation of L1 or S4 synthesis also inhibited cell growth. Overproduction of S11 did not affect synthesis of other r-proteins or alter growth. These results confirm previous in vitro studies [Yates, J. L., Arfsten, A. E. & Nomura, M. (1980) Proc. Natl. Acad. Sci. USA 77, 1837-1841] and support the hypothesis that certain r-proteins have the capacity to selectively inhibit synthesis of r proteins whose genes are in the same operon as their own. PMID- 6251472 TI - Comparative gene mapping: order of loci on the X chromosome is different in mice and humans. AB - For comparative studies we have used the somatic cell hybridization approach to regionally map genes on the mouse X chromosome. Fibroblasts from a mouse with the balanced reciprocal translocation T(XD;16B5)16H were fused with a Chinese hamster cell line (V79/380-6) deficient in activity of the enzyme hypoxanthine phosphoribosyltransferase (HPRT). Interpecific cell hybrids were initially selected for retention of the mouse translocation chromosome carrying the Hprt gene. Subsequently, hybrid clones were counterselected to force segregation of this chromosome. Selected and counterselected hybrid clones were analyzed for their chromosome content by trypsin/Giemsa banding and for expression of the mouse forms of the X-linked enzymes HPRT and alpha-galactosidase (GALA) by isoelectric focusing. The results indicate that the breakpoint on the mouse X chromosome (in band XD) has separated the genes for HPRT (Hprt) and for GALA (Ags). Hprt is proximal to the breakpoint in region Xcen-XD and Ags is distal in region XD-Xter. The gene order in the mouse (centromere-Hprt-Ags) is therefore inverted when compared to the order of the homologous loci on the long arm of the human X (centromere-GALA-HPRT). PMID- 6251473 TI - Polymorphism in mitochondrial DNA of humans as revealed by restriction endonuclease analysis. AB - Mitochondrial DNA samples from each of 21 humans of diverse racial and geographic origin were digested with each of 18 restriction endonucleases. The sizes of the resulting DNA fragments were compared after gel electrophoresis. No differences among the samples were detected in digest with 7 of the enzymes. Analysis of digests with the remaining enzymes showed one or more differences. Each of the 21 samples could be characterized individually on the basis of these digests. All between-sample differences could be explained by single base substitutions. No evidence for sequence rearrangements (inversions, transpositions) was obtained. Fourteen of the site alterations were shared by two or more samples; six of these were shared between races. The data indicate that individuals differ from a postulated ancestral mtDNA sequence at 0.18% of their base pairs. On the basis of an estimated rate for base substitution of 1% per 10(6) years [Brown, W. M., George, M., Jr. & Wilson, A. C. (1979) Proc. Natl. Acad. Sci. USA 76, 1967-1971], Homo sapiens could have speciated or passed through a severe population constriction as recently as 180,000 years ago. The data suggest that group specific patterns of cleavage exist. The high resolution and precision afforded by this method of analysis makes possible the investigation of many questions concerning human population genetics, evolution, and recent history. PMID- 6251474 TI - Nucleotide sequence of immunoglobulin heavy chain joining segments between translocated VH and mu constant regions genes. AB - To investigate the mechanism of recombination of immunoglobulin heavy chain variable and constant region genes, we have determined the nucleotide sequence of a large portion of the recombination region between an active C mu gene and its associated VH gene, isolated from an IgM-secreting mouse plasmacytoma, HPC76. By comparison with the sequence of the mu mRNA, we determined the exact boundaries of the intervening sequence between the VH76 and C mu genes. The rearranged VH76 gene encodes up to amino acid 116 without interruption, the 3' 39 nucleotides (the JH76 region) being derived from an embryonic JH segment (JH315) whose sequence was recently determined [Early, P., Huang, H., Davis, M., Calame, K. & Hood, L. (1980) Cell 195, 981-992]. The active JH76 does not use the first two codons of the embryonic JH315 from which it is derived. This indicates that V-J recombination is important in generating diversity within the third hypervariable region of heavy chains. We have identified another JH segment (JHA4), located 336 nucleotides 3' to the rearranged JH76 segment. This JH segment is expressed in the heavy chains of anti-levan myeloma proteins, which have truncated third hypervariable regions. We propose that the nucleotide sequence 5' to JHA4 is important for generating V region genes with shortened third hypervariable regions. PMID- 6251475 TI - Passive immunotherapy prevents expression of endogenous Moloney virus and amplification of proviral DNA in BALB/Mo mice. AB - BALB/Mo mice carrying the Moloney murine leukemia virus (M-MuLV) as an endogenous virus become viremic soon after birth and develop leukemia at a later age. M-MuLV specific gene expression and an increase of virus-specific DNA copies in lymphatic target organs are characteristics of the preleukemic phase. Passive immunotherapy of new born BALB/Mo mice with anti-gp70 glycoprotein or anti-M-MuLV serum prevented viremia and delayed significantly the subsequent development of leukemia. Molecular hybridization experiments showed that both virus-specific genome transcription and virus-specific DNA amplification could be completely suppressed by antiserum treatment. Thus virus-specific RNA concentrations in target organs of immunized BALB/Mo mice of 6 months or older were as low as in normal BALB/c mice. This is an age at which untreated BALB/Mo mice have already developed malignant lymphoma. Our experiments demonstrate that treatment with antiserum interferes with the early events of virus expression and thus prevents the subsequent steps leading to leukemia. PMID- 6251476 TI - Cloning of DNA complementary to the measles virus mRNA encoding nucleocapsid protein. AB - Double-stranded cDNA synthesized from total poly(A)-containing mRNA, extracted from monkey cells infected with measles virus, has been inserted into Pst cleavage site of Escherichia coli plasmid pBR322 and cloned. A clone containing measles virus DNA sequences was identified by hybridization to a measles virus specific 32P-labeled cDNA probe prepared from the mRNA of measles virus-infected cells. Cellular sequences in the probe were neutralized by prehybridization with an excess of unlabeled mRNA from uninfected monkey cells. The insert of cloned cDNA isolated contans 1420 base pairs, as shown by agarose gel electrophoresis and electron microscopy. The size of the mRNA complementary to this cloned cDNA is 1750 nucleotides, as determined by the reverse Southern technique. The cloned DNA fragment was further identified as the reverse transcript of the mRNA coding for the nucleocapsid protein of measles virus on the basis that the major cell free translation product of mRNA selected by hybridization to the cloned DNA comigrated with the nucleocapsid protein and was immunoprecipitated by measles virus-specific antibodies. Subsequently, the cloned DNA was used to detect specific measles virus sequences in the poly(A)-RNA extracted from brain autopsy material from a patient with subacute sclerosing panecephalitis. The cloned DNA can thus be used as a probe to study the structure and expression of the measles genome, and in particular, to study diseases of the central nervous system in which persistent infection with measles virus has been implicated. PMID- 6251477 TI - Multiple opiate receptors: [3H]ethylketocyclazocine receptor binding and ketocyclazocine analgesia. AB - The receptor binding of the kappa agonist [3H]ethylketocyclazocine to brain homogenates in vitro and ketocyclazocine (kappa) analgesia in vivo has been investigated and compared to morphine, a mu agonist. Saturation analysis of [3H]ethylketocyclazocine binding in both mice and rats yielded biphasic Scatchard plots similar to those of opiate mu agonists, antagonists, enkephalins, and endorphins. Treatment of brain membranes with monovalent and divalent cation, chelating agents, protein-modifying reagents, and enzymes affected [3H]ethylketocyclazocine binding in a manner similar to that of [3H]morphine. Naloxazone, a long-acting antagonist that selectively abolished high-affinity [3H DAla2,Met5]enkephalinamide binding in vivo, also selectively blocked high affinity [3H]ethylketocyclazocine binding. Evaluation of analgesia with writhing and tail-flick assays in animals whose high-affinity binding sites were blocked by naloxazone demonstrated a 6- to 7-fold increase in median effective dose (ED50) values of ketocyclazocine. This decrease in analgesic potency was comparable to morphine's decreased potency in similarly treated mice. These biochemical and pharmacological results suggest that the analgesic properties of both kappa and mu agonists may be mediated through the same subpopulation of receptors, the high-affinity binding sites. PMID- 6251479 TI - Growth potential of sheep and sea mammal cells transformed by SV40 early region DNA. PMID- 6251478 TI - Inhibition of AKR leukemogenesis by SMX-1, a dualtropic murine leukemia virus. AB - Intrathymic injection of SMX-1, a dualtropic murine leukemia virus (MuLV) originally derived from Moloney murine leukemia virus stocks, protects AKR mice from developing MuLV-accelerated leukemia and spontaneous leukemia. Thymuses of SMX-1-injected mice show no change in weight, morphology, or thymocyte size, and quantitative expression of Thy-1 and Lyt-2 differentiation antigens is identical to control mice. The amplified thymic expression of MuLV-related antigens that occurs spontaneously in 6-month-old preleukemic AKR mice or that can be induced in young AKR mice by leukemogenic AKR dualtropic MuLV is prevented by SMX-1. It appears unlikely that the protective effect of SMX-1 is explicable in terms of cross-immunogenicity with transforming MuLV or transformed cells. As SMX-1 persists for long periods after intrathymic injection and does not alter levels of thymic ecotropic MuLV, SMX-1 may interfere with the generation, spread, or leukemogenicity of dualtropic MuLV that form de novo in AKR thymus during the late preleukemic phase. SMX-1 provides a way to probe the events leading to cell transformation in AKR mice. PMID- 6251480 TI - Increased infectivity of oncogenic herpes viruses of primates with tumor promoter 12-O-tetradecanoylphorbol-13-acetate. PMID- 6251481 TI - Ascorbic acid inhibition of cyclic nucleotide phosphodiesterase acitivity. PMID- 6251482 TI - Activity of cyclic AMP-dependent protein kinase in heart and aorta of spontaneously hypertensive rat. PMID- 6251483 TI - Effects of chronic administration of antidepressant drugs on aggressive behavior induced by clonidine in mice. AB - The effects of antidepressant drugs on clonidine-induced aggressive behavior were determined in mice. Imipramine, mianserin and iprindole used in a single dose attenuated clonidine-induced aggression. Their chronic administration enhanced it. PMID- 6251484 TI - Caffeine potentiation of apomorphine discrimination. AB - Rats were trained to discriminate between the stimulus properties of intraperitoneal 0.16 mg/kg apomorphine and saline in a two-lever, food-motivated operant task. Apomorphine, at doses different than the training dose, produced a dose-response relationship, whereas, caffeine (7.5-30 mg/kg) produced saline-like responding. However, co-administered of 15 mg/kg caffeine with 0.01, 0.02 or 0.04 mg/kg apomorphine potentiated the discriminative stimulus properties of these low apomorphine doses. This potentiation was antagonized by pretreatment with 0.25 mg/kg haloperidol. The results are consistent with the idea that caffeine, by virtue of being a phosphodiesterase inhibitor, may increase post-synaptic cyclic AMP and this, in turn, may supersensitize the dopamine receptors and result in the potentiation of the apomorphine-induced dopaminergic responses. PMID- 6251485 TI - The evaluation of topological pharmacophores by heuristic approach. AB - A simple approach to evaluate logical pharmacophores on the base of topological features is described. It is based on considerations of the relative frequencies of structural features within different classes of activity. Shannon's entropy is used in the case of more than two classes. To obtain a pharmacophore a stepwise interactive procedure is performed. The algorithm is applied to fungicidal carboxamides and beta-adrenergic phenethylamine agonists and antagonists. In both cases meaningful pharmacophores could be obtained. PMID- 6251486 TI - Cyclic nucleotides, prostaglandins and polyamines in psoriasis. PMID- 6251487 TI - Effect on dental caries of a stannous fluoride-calcium pyrophosphate dentrifice in an adult population: one-year results. AB - The first year of a two-year double-blind clinical trial of the anticaries effectiveness of a stannous fluoride-calcium pyrophosphate (SnF2-CPP) dentifrice as compared to a placebo control dentifrice involved 1,337 adult subjects, 18 to 78 years of age. Adult subjects were examined for dental caries at a baseline examination and after one year of ad lib dentifrice usage by an experienced clinical examiner using a visual-tactile examination and a radiographic evaluation. Results of the study after one year indicate a significant (P < 0.05) 33.3% difference in new caries formation with use of the SnF2-CPP dentifrice as compared to the placebo control based on the DMFS score. PMID- 6251488 TI - Age-associated differences in guinea pig myocardial Na+, K+-ATPase activity and ouabain inhibition and in Mg2+-ATPase activity. AB - The influence of age on activity of cardiac Mg2+-ATPase and Na+, K+-ATPase from guinea pigs was studied. Tissue homogenates and NaI-washed membranes were prepared from the heart tissue of 10- to 12-day-old or greater than 12-month-old male guinea pigs. Tissue homogenates from the young animals had significantly greater enzyme activities than those from the older. Na+, K+-ATPase activity in young tissue preparations was less inhibited by ouabain than in older tissue preparations. These differences may be related to the observations that young animals and humans are less sensitive to cardiac glycosides than adults. PMID- 6251489 TI - Ventromedial hypothalamic lesions and stomach ulcers: reduction by non-nutritive bulk ingested in the post lesion period. PMID- 6251490 TI - Taste synergism between monosodium glutamate and disodium 5'-guanylate. AB - The examples of "synergism" reported in the taste literature fit the common definition of the term but may merely reflect normal additivity in the taste system. That is, the perceived intensities of these "synergistic" mixtures exceed the sums of the perceived intensities of the unmixed taste components (addition of perceived intensities), but do not exceed the perceived intensities predicted by adding along the expandng psychophysical functions which describe the unmixed taste components (stimulus addition). True synergism requires that the perceived intensity of a mixture be greater than that predicted by both types of additivity. Subjects used magnitude estimation to judge the perceived intensity of unmixed monosodium glutamate and disodium 5'-guanylate and mixtures of these two taste substances. The mixtures showed synergism according to both crtieria. The robustness of this phenomenon is striking; for all subjects the taste mixtures showed true synergism. True synergism in taste is an extremely rare phenomenon. PMID- 6251491 TI - Shock-induced fighting attenuates the effects of prior shock experience in rats. PMID- 6251492 TI - The influence of epinephrine on prostacyclin (PGI2) induced dissociation of ADP aggregated plateletes. AB - Prostacyclin (PGI2) is a powerful inhibitor of platelet function and recent studies have indicated that it can dissociate aggregated platelets in vivo. The present investigation has evaluated the mechanism involved in the dissociation of ADP aggregated platelets by PGI2, the influence of epinephrine on the process of PGI2 mediated disaggregation, and effects of the catecholamine on the refractory state of PGI2 dispersed cells. Dissociation of ADP aggregates by PGI2 was concentration and time dependent, caused complete disappearance of sensitive platelet clumps and restored platelet discoid form. The dispersed platelets were refractory to further stimulation by ADP, thrombin, arachidonate or the calcium ionophore, A23187. Measurement of cAMP revealed no change in control levels after aggregation by ADP, but a sharp increase during and after dissociation by PGI2. Epinephrine added to ADP aggregates before or after PGI2 blocked disaggregation, or stopped dissociation if already in progress, and caused a rapid fall in the high levels of cAMP stimulated by PGI2. Agents to which PGI2 dissociated platelets were refractory, including ADP, arachidonate and A23187 caused no lowering of elevated cAMP levels. Reduction of high levels of cAMP in PGI2 dispersed platelets by epinephrine did not result in reaggregation. However, epinephrine addition to refractory platelets restored in large measure their sensitivity to aggregation by arachidonate, thrombin, ADP and A23187. PMID- 6251493 TI - Effects of delta 9-tetrahydrocannabinol and cannabidiol on phospholipase and other enzymes regulating arachidonate metabolism. AB - delta 9-Tetrahydrocannabinol (THC) and cannabidiol (CBD) caused a marked stimulation of phospholipase A2 when incubated with intact human platelets that were prelabeled with [14C] arachidonate. CBD was about 1.5 x as potent as THC in the same concentration range (10 leads to 80 microM) Most of the released arachidonate was converted to lipoxygenae products. When [14C] arachidonate was incubated with lysed platelet extracts, THC inhibited both thromboxane synthetase and prostaglandin cyclooxygenase, so that the net effect was a redistribution of products toward the lipoxygenase pathway at the same time that a decrease in total cyclooxygenase product formation occurred. THC did not directly affect arachidonate lipoxygenase. Both TCH and CBD also stimulated release from prelabeled neuroblastoma cells (NBA2), which do not contain an active lipoxygenase pathway. In this case, accumulation of free arachidonate was detected by autoradiography. The multiple effects of THC and CBD on phospholipase A2 and arachidonate metabolism may mediate some of the pharmacological actions of these compounds, such as their anticonvulsant, anti-inflammatory, and hypotensive properties. PMID- 6251494 TI - Inhibition of platelet aggregation and elevation of cyclic-AMP levels in platelets by 13,14-dehydro PGI2 methyl ester. AB - 13,14-Dehydro PGI2 (dh-PGI2) and 13,14-dehydro PGI2 methyl ester (dh-PGI2-Me) inhibited platelet aggregation and release of [14C]-serotonin and ADP induced by collagen, ADP, arachidonic acid and PGG2. The inhibitory dose (ID50) ofg dh-PGI2 Me on platelet aggregation was 3 x 10(-9)M when induced with collagen, 2 x 10(-8) M with ADP, 5 x 10(-9) M with arachidonic acid and 1 x 10(-8)M with PGG2. The effects of dh-PGI2 and dh-POGI2-Me on platelet aggregation appear to be mediated by cyclic AMP, since both agents were potent to stimulate platelet cyclic AMP formation. In this respect dh-PGI2-Me was more effective than dh-PGI2 and PGE1. The actions of dh-PGI2-Me on platelet aggregation reported in this study suggest that is posseses similar biological properties as natural PGI2. Since dh-PGI2-Me is considerably more stable at physiological pH than PGI2 (Fried, J. and Barton, J. (1977) Proc. Natl. Acad. Sci. USA, 74, 2199-2203) this PGI2 analog might be useful as an anti-thrombotic drug. PMID- 6251495 TI - Adverse effects of Tris. HEPES and MOPS buffers on contractile responses of arterial and venous smooth muscle induced by prostaglandins. AB - The influence of artificial buffers, Tris, HEPES and MOPS, on PGA1, B2 and F2 alpha-induced contractile responses of isolated rat aorta and portal vein was investigated. All three buffers, in 5mM concentration, when substituted for bicarbonate and phosphate anions, differentially attenuated PG-induced contractile responses; the vein responses exhibited the greater sensitivity to artificial buffer inhibition. In the presence of the artificial buffers, the PG induced fast phase contractile components on the arterial smooth muscle were obliterated and the slow, tonic components were markedly depressed. PG contractile concentration-effect curves were shifted, differentially, to the right, concomitant with differential reductions in maximum tensions. Reincubation of the vascular tissues in normal Krebs-Ringer bicarbonate for 30-60 min resulted in a complete restoration of full PG-induced contractions. These results support the idea that Tris, HEPES and MOPS may interfere with the binding, translocation and utilization of calcium ions in vascular smooth muscle cells. One must be cautious regarding conclusions drawn for calcium-dependent responses obtained in smooth muscles in which Tris, HEPES or MOPS was the sole buffering agent. PMID- 6251496 TI - dl-9a-Deoxy-9a-methylene-PGI2 (a stable prostacyclin derivative): preliminary pharmacological data. AB - Carboprostacyclin (dl-9a-deoxy-9a-methylene-PGI2), a new stable PGI2-analogue, has been studied in vitro and in vivo. This analogue relaxes bovine coronary artery (potency ratio to PGI2 = 0.17), inhibits human PRP aggregation induced by ADP (IC50 = 12.5 nM2), deaggregates platelet clumps in cat heparinized blood (ED50 = 10.4 microgram/kg) and raises cAMP content in human PRP, but is less potent than PGI2. It is less potent (about 30 times) than PGI2 in lowering blood pressure in anaesthetized rats, inhibits basal gastric secretion in the rat and is 8 and 6 times less potent than PGE2 in protecting rat gastric mucosa from the lesions induced by stress and ASA, respectively, and about half as potent as PGE2 in protecting intestinal mucosa from damage by indomethacin. PMID- 6251497 TI - Alterations in maternal and fetal prostaglandin dehydrogenase as a result of maternal ethanol consumption. AB - Various lines of research have suggested that ethanol consumption may alter prostaglandin-related physiology. Our laboratory has reported that chronic exposure to high doses of ethanol lowers the ability of kidney and lung homogenates from rats to catabolize prostaglandin E2 and F2 alpha via 15 prostagladin dehydrogenase (PGDH). Because of the apparently unique role played by prostaglandins in conception, growth and development of the fetus and parturition, we have attempted to determine if the alterations observed in male rats also occur in females and if any alterations in fetal metabolism result from maternal ethanol exposure. Further, we have measured the influence of ethanol administration on renal clearance of the 15-keto metabolite of PGF2 alpha in an attempt to determine the in vivo significance of the enzyme inhibition observed in vitro. Initial results indicate the following. 1) Female Holtzman rats doses at 2.0, 5.0 and 7.0 mg ethanol/kg during the first, second, and third trimesters of pregnancy, respectively, showed losses in renal PGDH activity similar to those found in males (1.52 versus 1.05 picomole/min/mg, p < 0.001 by matched t-test). 2) Placental tissue (amnion) isolated from these same animals on day 21 of the pregnancies also showed a significant decrease in PGDH activity (14.79 versus 11.77 picomoles/min/mg, p < 0.01). 3) Kidney homogenates from fetuses delivered on day 21 of the pregnancies showed a significant increase in PGDH relative to pair-dosed controls (16.77 versus 12.65 picomoles/min/mg, p < 0.01). 4) In a separate experiment, urinary clearance of PGF2 alpha metabolite was inhibited in a dose related manner up to a level of 6 gm/kg. PMID- 6251498 TI - Decrease of eicosapentaenoic acid in fatty liver of diabetic subjects. AB - Simultaneous biopsies of liver and subcutaneous adipose tissue have been carried out in 228 patients with diabetes mellitus. In liver triglycerides a marked variability of the fatty acid pattern in relation to fatty degeneration of liver parenchyma has been confirmed. In adipose tissue fatty acid pattern was relatively constant. The most striking finding was a high content of eicosapentaenoic acid in normal liver and its decrease with the rise of lipid droplet size in the hepatocytes. No correlation with the quantity of liver fat or inflammatory liver diseases could be ascertained. When diabetes was associated with hyperlipoproteinemia (HLP) the percentage of eicosapentaenoic acid was significantly less. From the results the suggestion is obvious that a diminution of eicosapentaenoic acid in hepatic triglycerides is associated with lipid accumulation in the liver cells. A local mechanism, possibly the antilipolytic potency of prostaglandins, may be responsible for the creation of lipid droplets in liver cells of patients with metabolic disturbances. The alterations of eicosapentaenoic acid should be considered in view of recent data on the antiaggregatory effect of this fatty acid and its possibly preventive role for atherosclerosis. PMID- 6251499 TI - Influence of trifluoperazine on platelet aggregation and disaggregation. AB - Calmodulin has been shown to activate platelet phospholipase A2 and initiate the metabolism of arachidonic acid. Trifluoperazine (stelazine), an agent which selectively binds calmodulin, inhibits phospholipase activity induced by calcium. We have evaluated the effect of this agent on the aggregation, disaggregation and reaggregation of human platelets. Results of our study have shown that stelazine is a selective inhibitor of the second wave response of platelets to the stimulation of agonists. The compound causes dissociation of aggregated platelet clumps and induces a refractory state in dispersed cells. Epinephrine reverses the refractory state and potentiates the response of dissociated cells to the action of thrombin, arachidonate and ionophore A23187. Stelazine elevates cAMP levels to some extent and inhibits release of labeled arachidonic acid from platelet membranes in response to thrombin induced stimulation. Epinephrine may correct stelazine induced inhibition by acting through alpha-adrenergic mechanism, by inducing changes in membrane permeability to calcium, by releasing membrane associated calcium or by directly promoting deacylation of phospholipids. PMID- 6251500 TI - [Catamnestic examinations in a crisis intervention ward of a general hospital (author's transl)]. AB - The article reports on a catamnestic examination of patients of a crisis intervention center at a general hospital, conducted during the period from 1.5.1977 to 31.5.1978. A total of 560 admissions was recorded comprising 492 patients. Examination was carried out via an open questionnaire, plus data taken from the hospital's care index file. In 59% of the patients, the state of crisis was relieved in the course of an average hospitalisation period of 4.2 days; in 1.23% (= 6 patients), suicide occurred after hospitalisation. 2.4% only of the treated patients were re-admitted to inpatients treatment because of mental difficulties during the period of this study. Improvement of treatment is represented by the institution of facilities of transitional treatment which make it easier to transfer the patient from the crisis-intervention ward, motivating him to participate in long-term outpatient therapy. PMID- 6251501 TI - Effect of clonidine on growth hormone release in psychiatric patients and controls. AB - The stimulation of human growth hormone (HGH) release by clonidine (0.15 mg i.v.) was studied as a test of the postsynaptic alpha-receptor sensitivity of psychiatric patients. In this test, endogenous depressives showed a significantly reduced HGH response to clonidine as compared to normal controls, neurotic reactive depressives, and schizophrenics. However, no differences were found between the endogenous depressives and a group of schizoaffective patients. HGH response to clonidine was not correlated with plasma levels of noradrenaline, serum cortisol, free fatty acids, or blood glucose. Within the group of normal control subjects, a reduced HGH response was found in most postmenopausal women and in some regular users of alcohol. Our findings suggest that patients with endogenous depression are characterized by a subsensitivity of postsynaptic alpha receptors or of structures related to them. The clonidine test shows promise as an indicator of vulnerability to endogenous depression. PMID- 6251502 TI - Prolonged brainstem transmission time in autism. AB - Brainstem auditory evoked potentials (BAEPs) to clicks presented monaurally were gathered for 16 institutionalized children with a prior diagnosis of autism and with no hearing loss as tested by standard audiometry. Twenty age-matched normal children served as controls. Brainstem transmission time, defined as BAEP interpeak I-V latency, was prolonged significantly on the average in the autistic sample on both left and right sides. Individually, BAEPs for 9 of the 16 autistic children (or 56%) on whom some electrophysiological data were gathered were classified as abnormal when compared to the norms established in the control group. The most common BAEP abnormality was a prolonged interpeak III-V latency on the left side. PMID- 6251503 TI - Glucocorticoid effects on serotonergic and noradrenergic facilitation of spinal monosynaptic transmission. AB - The ability of an intensive glucocorticoid regimen (i.e., triamcinolone diacetate, 8 mg/kg i.m./7 days) to modify the lumbar spinal monosynaptic reflex response to serotonergic and noradrenergic agents has been examined in unanesthetized acute spinal (C-1 sectioned) cats. Triamcinolone pretreatment enhances the 2N facilitatory actions of amitriptyline (AMIT), 5 mg/kg i.v., when given after D,L-5-hydroxytryptophan (5--HTP), 50 mg/kg i.v., as compared to untreated control preparations. Subsequent administration of methysergide, a serotonin receptor blocking drug, in a dose of 1 mg/kgh i.v. promptly and completely reverses the monosynaptic response increase by AMIT in untreated animals, but not in the glucocorticoid treated ones. In contrast, the monosynaptic facilitation normally produced in untreated preparations by methoxmine (MX), 1 mg/kg i.v., a centrally active noradrenergic agonist, is prevented as a result of triamcinolone dosing. These results demonstrate a glucocorticoid effect on spinal biogenic amine function such that serotonergic monosynaptic reflex activation is enhanced while noradrenergic reflex stimulation is depressed. Furthermore, they suggest that the elevations in plasma cortisol in certain cases of psychiatraic depression may; contribute to alterations in central biogenic amine synaptic activity. PMID- 6251504 TI - Short-term hormonal effects of naloxone in man. PMID- 6251506 TI - The role of cation-activated ATPases in transmitter release from the rat iris. AB - Release of noradrenaline (NA) from isolated rat iris during perfusion in K+-free medium was confirmed. Direct biochemical measurement of different cation activated ATPases did not reveal any definite relationship between Na+K+ ATPase and NA release. A significant increase in Ca++Mg++ ATPase activity was found on termination of NA release obtained by reintroduction of K+ to the medium. Criticism of the model for studying enzymatic control of transmitter release under physiological conditions is presented. It is suggested that removal of intracellular Ca++ ions by a calcium pump is directly associated with termination of transmitter release. PMID- 6251505 TI - The mechanism of action of delta 9-tetrahydrocannabinol on body temperature in mice. AB - The effect of delta 9-tetrahydrocannabinol (delta 9-THC) on body temperature of the mouse was studied. A dose-response relationship (5-100 mg/kg) for the hypothermic effect of delta 9-THC was seen. The investigation as to the mechanism underlying the hypothermic action of delta 9-THC was also investigated. The relatively specific dopamine antagonist haloperidol potentiated delta 9-THC induced hypothermia as did the alpha-adrenoceptor antagonist phenoxybenzamine. However, depletion of serotonin with P-chlorophenylalanine reduced the hypothermic response to delta 9-THC as did pretreatment with the serotonin antagonist methysergide. Inhibition of re-uptake of serotonin with clomipramine potentiated the hypothermia following delta 9-THC. It is suggested that the hypothermic effect of delta 9-THC in the mouse is mediated to a large extent via serotonergic mechanisms. PMID- 6251507 TI - The effect of naloxone on the inhibition of nociceptor driven neurones in the cat spinal cord. AB - The functional role of the opiate receptors and enkephalins found in high concentration in the superficial dorsal horn of the spinal cord has not been ascertained but may be the modulation of transmission in nociceptive pathways. In cats anaesthetized with alpha-chloralose the nacrotic antagonist, nalozone, was tested on various types of inhibitory input to spinal cord neurones which responded to both noxious and non-noxious stimulation of their receptive fields (Class 2 neurones). Naloxone (0.3-2.0 mg/kg i.v.) failed to alter the response of these neurones to noxious radiant heat, to tonic descending inhibition or to inhibition evoked by stimulation of the dorsal columns or contralateral plantar nerve. Thus the endorphins do not appear to be involved in mediating the types of inhibition examined. On the other hand, i.v. morphine reduced the response of Class 2 neurones to noxious heating of the skin that was reversed by naloxone. PMID- 6251508 TI - Cancer invasion and metastasis. AB - Metastasis, the spread of neoplastic cells from a primary site to distant organs, is responsible for the majority of cancer deaths. Dissemination of malignant cells throughout the body and their survival to form secondary growths is a complicated process dependent on both host and tumor properties. Although a primary tumor may release many cells, only a few survive the interactions with host defense mechanisms to yield distant cancer growths. In recent years a considerable body of evidence has accumulated which suggests that the survival of these few cells is not a random event. Rather, it represents the selection of a pre-existent metastatic subpopulation of tumor cells within the parental population. Such a process has profound implications in determining approaches to therapy and to the elucidation of those tumor-cell properties which are responsible for successful metastatic spread. These implications are discussed within the framework of what is at present known about the pathogenesis of cancer metastasis. PMID- 6251509 TI - Neutron irradiation of bacteria in the presence and absence of secondary charged particle equilibrium. PMID- 6251510 TI - Variation in cyclic nucleotide levels and lysosomal enzyme activities in the irradiated rat. PMID- 6251511 TI - [Joint use of aminopropylaminoethylthiophosphate with other radioprotective agents]. PMID- 6251512 TI - Modulation of autonomic neurotransmission by PGD2: comparison with effects of other prostaglandins in anesthetized cats. AB - Experiments with anesthetized cats were done to study possible roles of different prostaglandins (PGs) in modulating sympathetic neuroeffector transmission. We recorded contractions of the nictitating membrane (n.m.), blood flow in the carotid artery, heart rate and blood pressure, both under control conditions and while stimulating the cut cervical sympathetic nerve. Intra-carotid arterial injection (i.a.) of PGD2 depressed sympathetic transmission to the n.m. without depressing the effects of exogenous norepinephrine (NE). In contrast, PGE2 enhanced the effects of nerve transmission or exogenous NE on the stimulated n.m. PGI2 had similar but shorter effects to PGE2. PGF2 alpha or a stable PGH2 analog, contracted the n.m. smooth muscle with no detected effect on nerve transmission. Carotid blood flow was increased by PGD2, PGE2 and PGI2. PGD2 and PGI2 caused bradycardia that could be blocked by atropine. This ability of PGD2 to modulate autonomic nerve activity is of particular interest because of recent reports that nerve tissue synthesizes PGD2. PMID- 6251513 TI - 6-keto-prostaglandin E1 is not equipotent to prostacyclin (PGI2) as an antiaggregatory agent. AB - A direct comparison of the relative potencies of the two antiaggregatory prostaglandins PGI2 and 6-keto-PGE1 showed PGI2 was at least 20 times more potent than 6-keto-PGE1 when tested against ADP-induced human platelet aggregation. This marked difference in potency was even more evident when the ability of PGI2 and 6 keto-PGI2 to stimulate platelet cyclic AMP levels was determined. When cyclic AMP levels were measured direct comparisons were difficult because the respective dose response curves were not parallel, but 10 ng of PGI2 was equivalent to 300 ng of 6-keto-PGE1. PGI2 was also more potent (10-20 times) than 6-keto-PGE1 as a disaggregatory agent, and the disaggregatory activity of both prostaglandins was enhanced by the phosphodiesterase inhibitor 1-methyl-3-isobutylmethylxanthine. PGI2 was also more active than 6-keto-PGE1 as an inhibitor of thrombus formation in dog coronary arteries in vivo. In vivo, 6-keto-PGE1 was at least 10 times less potent thatn PGI2, the exact difference could not be determined because 6-keto PGE1 caused significant falls in blood pressure before anti-platelet activity could be detected. PGI2 is an intrinsically more potent anti-aggregatory molecule than 6-keto-PGE1, but these data do not rule out the possibility that some of the activities attributed to PGI2 could be the result of the conversin of PGI2 and/or 6-keto-PGF1 alpha to 6-keto-PGE1. PMID- 6251514 TI - Chemokinetic activity of arachidonic and lipoxygenase products on leuocyctes of different species. AB - A number of hydroperoxy (HPETE) and hydroxy (HETE) products of the lipoxygenase pathway of arachidonic acid metabolism are chemotactic and chemokinetic for human neutrophils. We have investigated the relative chemokinetic potency of some of these products on human, rat and rabbit neutrophils. The most potent lipoxygenase product studied was 5,12-dihydroxy-6,8,10-14-eicosatetraenoic acid (5,12-diHETE), which was maximally chemokinetic and chemotactic between 0.1 and 1.0ng/ml for the three species. The 5, 11 and 12-HPETEs and HETEs were chemokinetic, but less active by at least two orders of magnitude, for human and rabbit neutrophils at concentrations between 0.1 and 10micrograms/ml. 15-HPETE and 15-HETE were inactive on human leucoctes, and none of the monosubstituted products studied were chemokinetic for rat neutrophils. These results indicate that 5,12-diHETE may be an important mediator in the local accumulation of leucocytes in the inflammatory response. PMID- 6251515 TI - Studies on phage internal proteins. VI. Interaction of bacteriophage T4 internal proteins with T4 DNA in vivo and in vitro. AB - Internal proteins are basic proteins bound to the DNA of T4 coliphage. Centrifugation in sucrose gradients was employed to isolate DNA-internal proteins complexes formed in vitro. Polyacrylamide gel electrophoresis of radioactive internal proteins in the presence of sodium dodecyl sulfate followed by autoradiography of the gels was used to identify the DNA-bound proteins and to determine their respective abundance in these complexes as well as in the bacteriophage head. The internal proteins were found to bind to the phage DNA (in vitro experiments) at the same ratio as that of internal proteins associated with the viral DNA within the phage head (in vivo binding). PMID- 6251516 TI - [Hepatocarcinoma in giant solitary congenital cyst of the liver]. PMID- 6251517 TI - Steroid hormone receptors in breast cancer treatment strategy. PMID- 6251518 TI - ACTH, beta-lipotropin, and related peptides in brain, pituitary, and blood. PMID- 6251519 TI - Hormones controlling insect metamorphosis. PMID- 6251520 TI - Autoimmunity in endocrine disease. PMID- 6251521 TI - Regulation of peptide hormone receptors and gonadal steroidogenesis. PMID- 6251522 TI - Effects of general central nervous system depressants with and without calcium ionophore A23187 of rat cerebellar cyclic guanosine 3',5'-monophosphate. AB - Rat cerebellar cyclic guanosine 3',5'-monophosphate (cGMP) concentrations were determined by radioimmune methods after sacrifice with focused microwave fixation in animals pretreated with either ethanol, pentobarbital, or diethyl ether, either alone or in combination with the calcium ionophore A23187. Both pentobarbital sodium and diethyl ether produced a dose-dependent depression of cerebellar cGMP. When A23187 was administered alone, significant increases of cerebellar levels of cGMP were observed. The administration of A23187 to animals acutely intoxicated with ethanol, pentobarbital, or diethyl ether resulted in significant depression of cerebellar cGMP levels. PMID- 6251523 TI - Evidence for the presence of an endogenous inhibition of prolyl hydroxylase. AB - Prolyl hydroxylase [EC 1.14.11.2] was shown to be inhibited by an ultrafiltrate (less than 30,000 molecular weight) fraction isolated from skin and blood of neonatal and adult rabbits. This fraction also inhibited two other alpha ketoglutarate requiring mixed function oxidases, lysyl hydroxylase [EC 1.14.11.4] and alpha-butyrobetaine hydroxylase [EC 1.14.11.1] but not the amine oxidase, lysyl oxidase. Purification of the skin ultrafiltrate on Sephadex G-25 demonstrated a peak of prolyl hydroxylase inhibitory activity which chromatographed at a molecular weight corresponding to approximately 3,000. Chromatography of a blood ultrafiltrate separated a similar peak of material which was inhibitory for prolyl hydroxylase. PMID- 6251524 TI - Evaluation of the double immunodiffusion test for the diagnosis of louping ill infection. AB - The usefulness of the double immunodiffusion test for the diagnosis of louping ill infection was investigated. Whereas louping ill viral antigen was not detected in brain material from field cases of the infection, its presence was readily confirmed in suckling mouse brain isolates of the virus. The double immunodiffusion test was found to be unreliable as a serological test for the retrospective diagnosis of louping ill infection in the horse. PMID- 6251525 TI - Response of caeruloplasmin to Escherichia coli endotoxins and adrenal hormones in the domestic fowl. AB - The injection of chickens with Escherichia coli endotoxins immediately produced a 50 per cent rise in plasma caeruloplasmin activity which was attributed to the release of the protein from liver cell. This was followed by a fall in activity, which was probably due to a fall in activity, which was probably due to a stabilising effect of adrenocortical hormones on the cell membranes, and then by a five-fold increase. The results of experiments with cycloheximide, adrenocorticotrophin, beta-methasone and reserpine indicated that the third phase of the response reflected increased synthesis in the liver which was partly induced by adrenal hormones. It increased with the dose and was not elicited by the particulate nature of the toxin preparation or by its lipid and polysaccharide components. PMID- 6251526 TI - Survival of Aujeszky's disease virus in frozen pig meat. AB - The survival of Aujeszky's disease virus was studied in muscle, lymph node and bone marrow frozen at -18 degrees C, following infusion of a large dose of the virus into the hindquarter of a freshly killed pig. Previous attempts to induce an adequate viraemia for such studies, using intranasal and intravenous routes of inoculation of large doses of virus in live pigs, were unsuccessful. In frozen meat and marrow, the virus showed a biphasic inactivation curve with time, similar to that seen with cell-cultured virus. Most virus was rapidly inactivated initially but a small population of more stable virus persisted for a considerable period of time. In contrast, virus in lymph node showed a uniform inactivaton rate, like that of the more stable componet only. Virus was not detectable in any of the tissues after 35 days of storage at -18 degrees C. PMID- 6251527 TI - Cytomegalovirus immunization: status, prospects, and problems. AB - The cytomegaloviruses (CMV), members of the herpesvirus group, are widely disseminated; however, among healthy, nonpregnant adults these viruses are not usually responsible for serious illness or disability. However, CMV infections associated with pregnancy are an important cause of prenatal infection and are significantly associated with sensorineural injury and mental retardation in the offspring of infected mothers. CMV infections also constitute a significant threat to patients with disseminated malignancies, to allograft recipients, and to others who are debilitated and immunosuppressed. The development of a program of immunization against CMV has been proposed as a means to control prenatal infection and injury as well as to reduce the relevant morbidity and mortality of these infections among allograft recipients and others at high risk. In this review the potential benefits, problems, and risks associated with CMV immunoprophylaxis are discussed and results of preliminary trials of prototype CMV vaccines are presented and evaluated. PMID- 6251528 TI - Approaches to immunization of infants and young children against gastroenteritis due to rotaviruses. AB - Recent studies have shown that in developed countries rotaviruses are the single most important etiologic agents of acute gastroenteritis that requires hospitalization of infants and young children. Although deaths from gastroenteritis are, in general, infrequent in the developed countries, an effective rotavirus vaccine would clearly be of benefit to reduce the heavy toll of morbidity from gastroenteritis due to rotavirus. In the developing countries the impact of diarrheal diseases is staggering. It was recently estimated that in Asia, Africa, and Latin-America during a one-year period there would be 3.5 billion cases of diarrhea and 5-10 million deaths associated with diarrhea; in addition, diarrhea was ranked first in freqency in the categories of disease and mortality. In the developing countries rotaviruses are known to cause diarrhea, but their relative role in this high mortality rate is not yet known. epidemiologic data indicate that development of an effective rotavirus vaccine would reduce morbidity, and they suggest that a vaccine would also reduce a portion of the mortality from diarrheal disease. The prospects and approaches for the development of an effective rotavirus vaccine are presented. The recent successful propagation of rotavirus type 2 in cell culture represents an important step in this regard. In addition, the antigenic relation between human and animal strains offers another possible approach. The need for a live attenuated vaccine is indicated by the prime role played by local intestinal immunity in resistance to rotavirus disease. PMID- 6251529 TI - Classics in infectious diseases. The cultivation of the poliomyelitis viruses in tissue culture by John F. Enders, Frederick C. Robbins, and Thomas H. Weller. PMID- 6251530 TI - Congenital disorders of the function of polymorphonuclear neutrophils. AB - This review has concentrated on clinical syndromes for which a congenital basis of polymorphonuclear neutrophil dysfunction has been identified. The first clinical syndrome found to be associated with dysfunctional polymorphs was chronic granulomatous disease of childhood. Identification of a cellular defect in oxidative metabolism and microbicidal activity of polymorphonuclear neutrophils from patients with CGD stimulated intense investigation of the function of phagocytes in several clinical entities characterized by increased susceptibility to infection. Other diseases with a probable congenital basis for polymorph dysfunction include Chediak-Higashi syndrome, myeloperoxidase deficiency, severe glucose-6-phosphate dehydrogenase deficiency, and Down's syndrome. Functional defects have also been identified in neutrophils with morphologic abnormalities, such as the Pelger-Huet anomaly and the May-Hegglin anomaly, and in neutrophils without alkaline phosphatase or with a disorder of the glutathione system. The evidence for a relation between these cellular disorders and susceptibility to infection is tentative. Patients with congenital disorders of polymorphonuclear neutrophil microbicidal function frequently suffer prolonged infections in spite of appropriate antimicrobial therapy, and severe lesions recur with discouraging frequency. These lesions are usually soft tissue or bone abscesses, and the etiologic agents are typically staphylococci, gram negative enteric species, or fungi. The infectious disease problems of patients with phagocytic cell disorders are usually quite distinct from the problems of patients without immunoglobulins or with complement deficiency. Patients with agammaglobulinemia, for example, suffer recurrent septicemia or meningitis due to Streptococcus pneumonia or H. influenzae. Septicemia, especially with the pyogenic bacterial species, is unusual in patients with polymorphoinuclear dysfunction. A major contribution of the currently intense investigation of cells from patients with congenital disorders of phagocyte function has been the greatly increased understanding of the molecular events necessary for the normal function of these cells. The role of the oxidative metabolic burst during phagocytosis has been clearly identified as essential to the microbicidal function of polymorphs and monocytes, and the glutathione system has been identified as essential to the regulation of these oxidative reactions. It is anticipated that these studies may lead to practical methods for "stimulating the phagocytes" in patients with increased susceptibility to infection. PMID- 6251531 TI - [Whip-lash injury and the two last skull nerves damage. Two cases (author's transl)]. PMID- 6251532 TI - [Etiology of colonic and rectal cancer]. PMID- 6251533 TI - Microbiology of the canine nasal cavities. AB - The anterior and superior regions of canine nares yielded two distinct microbial populations consisting of 25 microbial species. Streptococci predominated in the anterior nose; clostridia and staphylococci were also quite prevalent. At least two distinct microorgranisms were cultured from most anterior sites. In contrast, sterile conditions prevailed in the superior nasal regions of at least 50% of the ninety-two animals. Various Bacillus sp. were recovered from the remainder. PMID- 6251535 TI - Enzyme activities, fibre types and capillarization in calf muscles of patients with intermittent claudication. PMID- 6251534 TI - Liberation of a fibrogenic factor from human blood monocytes, ascites cells, cultured histiocytes and transformed mouse macrophages by treatment with SiO2. AB - Human monocytes and ascites macrophages from cirrhotic patients were isolated in Percoll-gradient and cultured with and without silica. Similar experiments were carried out also with cultured malignant human histiocytes and transformed mouse macrophages. The fibrogenic activity of the culture media was tested by measuring the incorporation of [3H]proline and [3H]thymidine into cultured rat granuloma and human synovial cells. Media from silica-treated monocytes, ascites macrophages and certain histiocyte and mouse macrophage lines caused an increase in the incorporation of both [3H]proline and [3H]thymidine into collagen and DNA, respectively, in both cell systems. Alkaline RNase activities were decreased markedly in the media from silica-treated ascites macrophages but not in the media of the monocytes or histiocytes. PMID- 6251536 TI - Molecular and morphological evidence for type B retrovirus (oncornavirus) expression in human mammary carcinoma. An overview using scanning electron microscopy, immunoperoxidase staining, and transmission electron microscopy. AB - Approximately 45% of human mammary carcinoma cases express an antigen which cross reacts in formalin fixed tissues with antiserum prepared against the purified 52,000 molecular weight structural glycoprotein (gp52) of mouse mammary tumor virus (MMTV). Breast carcinoma immunoperoxidase marking is abolished by antiserum adsorption with MMTV. Adsorption with murine leukemia virus failed to block immunoperoxidase marking. No correlation was seen in the cases analyzed between gp52-like antigen expression and family history of mammary carcinoma, age, or pathological classification. The evidence linking an oncornaviral agent in human mammary carcinoma is reviewed with respect to the structure and biology of a known etiological agent, MMTV, in murine mammary cancer. The potential role of SEM in amplifying the surface area available for analysis in malignant and premalignant human breast epithelia is considered. PMID- 6251537 TI - Surface configuration of human tumor cells obtained by fine needle aspiration biopsy. AB - Surface configuration of viable cancer cells freshly aspirated from various malignant tumors such as mammary carcinoma, renal carcinoma, malignant melanoma and oat cell carcinoma were described. Various aspects of surface configuration of tumor cells ranging from numerous microvilli, blebs or ridges, to almost entirely smooth surfaces were found. Microvilli were most commonly seen on surfaces of tumor cells from carcinoma of the breast and from malignant melanoma. There were no specific surface features for any of the tumor cells studied except for oat cell carcinoma. This is in contradistinction to the configuration of cancer cells in effusions wherein most cancer cells are covered by dense, irregular microvilli. PMID- 6251538 TI - Immunoelectron microscopic studies using monoclonal antibodies to mouse mammary tumor virus antigens as probes of the cell surface with the unlabeled antibody hemocyanin bridge. PMID- 6251539 TI - Use of backscattered electron imaging to quantify the distribution of inhaled crystalline silica. AB - Inhalation of crystalline silica causes fibrotic pulmonary disease. The lung pathology of silicosis is well characterized and predictable, but the initial patterns of particle deposition and translocation are unknown. Scanning electron microscopy and backscattered electron imaging were utilized to quantify silica particle distribution in the distal air spaces of rats following a three-hour exposure to silica dust at a concentration of 100mg/m3. Lungs were perfused through the vasculature with 2% Karnovsky's fixative at a pressure of 15cm of water for 30 minutes. Blocks of tissue were dissected from five predetermined regions of the left lung and critical point dried. Mounted blocks were further dissected to reveal terminal bronchioles and their attached alveolar ducts. The tissue was sputter-coated with gold. Silica particles were visualized on the alveolar duct surfaces, then counted using negative backscattered electron imaging. The precise area of alveolar duct surfaces was calculated by using a standard magnification of 10,000X and a grid of 64cm2 over the viewing cathode ray tube. Thus, quantitation of silica particles could be expressed as number of particles per square micron. Our data show that there were fewer particles on the alveolar duct surfaces and in alveolar spaces of animals 8 hours after exposure when compared with animals 3 hours post-exposure. PMID- 6251540 TI - The surface appearance of some lung tumors, mesothelioma and their precursor lesions. PMID- 6251541 TI - A revolution in biology. PMID- 6251542 TI - Steps toward computer analysis of nucleotide sequences. AB - Advances in recombinant DNA technology have allowed the isolation of large numbers of biologically interesting fragments of DNA. Concomitant improvements in methods for nucleic acid sequencing have led many investigators to characterize their clones by sequencing them. This has resulted in the accumulation of such large amounts of sequence data that computer-assisted methods, with programs directed toward the manipulation of nucleic acid sequences, have become indispensable during the collection and analysis of that data. PMID- 6251543 TI - Phase variation: evolution of a controlling element. AB - Phase variation in bacteria is regulated by homologous recombination at a specific DNA site. This recombinational event causes the inversion of a 970-base pair DNA sequence that includes the promoter necessary for transcription of a flagellar gene. The invertible segment is flanked by two sites that are necessary for the inversion and contains a gene (hin) whose product mediates the inversion event. The hin gene shows extensive homology with the TnpR gene carried on the Tn3 transposon. It is also homologous with the gin gene carried on bacteriophage mu. These relationships suggest that the phase variation system may have evolved by the association of a transposon with a resident gene and the subsequent specialization of these elements to regulate flagellar antigen expression. PMID- 6251544 TI - The origins of gene instability in yeast. AB - Two unstable mutations at the his4 locus of yeast are due to the insertion of the transposable elements Ty912 and Ty917 into the his4 regulatory region. The two transposons are related, one being derived from the other by a substitution of 4000 base pairs of DNA. Element Ty912 includes identical terminal repeats, whereas the terminal repeats of Ty917 are not identical. Transposition of Ty912 or Ty917 generates 5-base-pair duplications of the target DNA at either end of the element. Expression and reversion of a his4 gene containing Ty912 or Ty917 is controlled by three unlinked regulatory genes. The properties of these regulatory genes are similar to those described for the controlling elements in maize. PMID- 6251545 TI - Recombination of dispersed repeated DNA sequences in yeast. AB - Yeast transformation can be used to insert new sequence arrangements into a variety of chromosomal locations by homologous recombination. These newly inserted sequences can recombine with similar sequences located on other chromosomes. In these events, information is duplicated without being lost at the site from which it is derived. Similar mechanisms might be utilized by cells to provide new functions during development or differentiation. PMID- 6251546 TI - Tumor DNA structure in plant cells transformed by A. tumefaciens. AB - Crown gall tumors are induced in plants by infection with the soil bacterium Agrobacterium tumefaciens. Because the tumor induction involves transfer of a portion of the tumor-inducing (Ti) plasmid DNA from the bacterium to the plant cells, this system is of interest for the study of genetic exchange as well as tumor induction. The boundaries of the transferred DNA (T-DNA) have been cloned from transformed plant cells of tobacco. Detailed mapping with restriction enzymes and nucleotide sequence analysis of two independent clones were used to study the molecular structure of the ends of the T-DNA. One clone contains the two ends of the T-DNA joined together; the other contains one end of the T-DNA joined to repetitive plant DNA sequences. These studies provide direct evidence that the T-DNA can be integrated into the plant genome. In addition, the data suggest that in the plant, T-DNA can be tandemly repeated. Sequence analysis of the junction of crown gall clone 1 reveals several direct repeats as well as an inverted repeat; these structures may be involved in the transfer of the DNA from Agrobacterium to plant cells. PMID- 6251547 TI - Isolation of mutants of an animal virus in bacteria. AB - Mutants of animal viruses can be isolated in bacteria by recombinant DNA methods. Since no viral functions are required for propagation of recombinants in bacteria, viral mutants with lethal changes in cis- or trans-acting elements can be isolated, as well as partially or conditionally defective mutants. In the cases of viruses with small DNA genomes, such as the tumorigenic simian virus 40 (SV40), the entire viral DNA can be inserted into the bacterial plasmid pBR322 and cloned in Escherichia coli. Recombinant plasmids with a single copy of SV40 DNA cause morphological transformation of mouse cells in culture with the same efficiency as SV40 DNA isolated from virus-infected monkey cells, but the recombinant DNA is noninfectious and replicates poorly in permissive cells. However, SV40 DNA excised from the plasmid replicates as well as authentic viral DNA and is fully infectious. SV40 mutants with small deletions or base substitutions have been isolated by in vitro site-specific or random local mutagenesis of recombinant DNA followed by cloning in E. coli. Many of the mutants thus isolated are defective in specific viral functions. PMID- 6251548 TI - Promoter sequences of eukaryotic protein-coding genes. AB - In vitro genetic techniques were used to study the sequence requirements for the initiation of specific transcription. Deletion mutants were constructed around the putative promoter of the adenovirus-2 major late and chicken conalbumin genes. Specific transcription in vitro by RNA polymerase B together with a HeLa cell cytoplasmic extract was used as the test for promoter function. With this approach sequences which are essential for the initiation of specific transcription in vitro, were shown to be located between 12 and 32 base pairs upstream from the 5' end of these genes. PMID- 6251549 TI - Expression of a bacterial gene in mammalian cells. AB - Transfection of cultured monkey kidney cells with recombinant DNA constructed with a cloned Escherichia coli gene that codes for xanthine-guanine phosphoribosyltransferase and several different SV40 DNA-based vectors, results in the synthesis of readily measurable quantities of the bacterial enzyme. Moreover, the physiological defect in purine nucleotide synthesis characteristic of human Lesch-Nyhan cells can be overcome by the introduction of the bacterial gene into these cells. PMID- 6251550 TI - Long-term antidepressant treatment decreases spiroperidol-labeled serotonin receptor binding. AB - Antidepressants compete at several neurotransmitter receptor binding site, but drug affinities do not correlate with clinical efficacy. Long-term, but not short term, antidepressant treatment decreases the numbers of both serotonin and beta adrenergic receptors. The decrease in the number of receptor sites is most marked for [3H]spiroperidol-labeled serotonin receptors and is characteristic for antidepressants of several classes. PMID- 6251552 TI - Asymmetry of the acetylcholine channel revealed by quaternary anesthetics. AB - Tissue-cultured rat myoballs were examined electrophysiologically with a suction pipette, which was used for voltage clamping and internal perfusion. The lidocaine derivative QX-314 caused a time- and membrane potentia-dependent block of acetylcholine-induced current only when applied from the extracellular membrane surface. The same compounds caused a use-dependent block of the sodium channel only from the intracellular membrane surface. These experiments demonstrate a fundamental asymmetry of the acetylcholine receptor-channel complex. PMID- 6251551 TI - Photosynthesis of previtamin D3 in human skin and the physiologic consequences. AB - Photosynthesis of previtamin D3 can occur throughout the epidermis in the dermis when hypopigmented Caucasian skin is exposed to solar ultraviolet radiation. Once previtamin D3 is formed in the skin, it undergoes a temperature-dependent thermal isomerization that takes at least 3 days to complete. The vitamin D-binding protein preferentially translocates the thermal product, vitamin D3, into the circulation. These processes suggest a unique mechanism for the synthesis, storage, and slow, steady release of vitamin D3 from the skin into the circulation. PMID- 6251554 TI - [Cyto-colposcopic and epidemiologic study of uterine cancer (author's transl)]. AB - 11 364 systematical gynecological items including colposcopy and cytology have been performed in the specialized consultation of the "Centre des Examens de Sante de la Gironde". 58 severe dysplasias and cancers were found, all of them by tissue section. The efficiency of this screening amongst a non selected population is of 0,51 per cent. This study, the results of which are compared to a few recent statistics, is an approach to a regional epidemiologic research, upon uterine carcinomas. It may define a high risk group which should benefit a more frequent survey. PMID- 6251553 TI - [Compensatory renal hypertrophy (CRH) (author's transl)]. AB - CRH is now well established. Theorical study shows arterial and tubulary changes after nephrectomy. These studies show also the mechanism of CRH: the presence of a growth inhibiting substance and also the presence of stimulating agents transmitted humorally for stimulating and inhibiting substance to be able to act in a coordinated way. There must be a negative feed back control mechanism. Clinical application of thoses findings are very important. PMID- 6251555 TI - [Treatment of headache with tiapride (author's transl)]. AB - The therapeutic effect of tiapride was studied in 54 patients attending a neurological department for various types of headaches. In most cases these had been present for several years and were resistant to treatment. The average dosage of tiapride was one tablet three times per day. The headache had completely disappeared after treatment in 17 patients. In 28 patients they reappeared after discontinuing treatment but disappeared again when tiapride was again administered. The symptom persisted in 9 patients. Best results were obtained in post-traumatic and psychogenic headaches and in migraine. Results were less successful in headaches occurring in epileptic patients. Tolerance was good and no significant extrapyramidal, neurovegetative, or neuro-endocrine effects were observed. PMID- 6251556 TI - [The thyroxine hyperthyroidism (author's transl)]. AB - 24 of all patients observed between 1974 and 1976 suffering from thyrotoxicosis were found to have increased blood thyroxine (T4) levels without increased triiodothyronine ones. T4 hyperthyroidisms represented 3.5% of all hyperthyroidisms observed; they were in relation with Grave's disease (18 patients) or toxic nodular (6 patients); clinical pictures were quite usual; old age, severe illnesses, amiodarone and corticoids treatments, iodine excess, were sometimes being incriminated, but often no particular cause could be found. Preferential T4 secretion or impaired peripheral T4 conversion are two possible mechanisms of T4 hyperthyroidism. PMID- 6251558 TI - [Portal hypertension thermographic aspects (author's transl)]. AB - From the study of 80 patients, the authors show the interest of abdominal thermography to explore a portal hypertension. Linear stripes, stellar pictures, periumbilical hot spot are specific pictures. These thermographic modifications come before cutaneous venous signs in half of the population. Their interest for prognosis remains to be specified. PMID- 6251557 TI - [Study of 104 patients with renal polycystic disease (author's transl)]. AB - Hereditary factors were observed in 43% of patients. Hypertension was observed in 45% of cases and was not correlated with the degree of renal insufficiency. Serum creatinine was significantly correlated with calcemia and uricemia. Identical correlations were observed in a population of patients whose renal insufficiency was not related to renal polycystic disease. The study provides evidence that, in polycystic kidneys: 1) Hypertension is not related to the degree of renal failure. 2) Hypocalcemia and hyperuricemia are not specific factors of the disease. PMID- 6251559 TI - [Renal arteriovenous fistulae after nephrectomy: report of a case and review of the published literature (author's transl)]. AB - The authors review the principal etiological, pathogenic, clinical and radiological features of post-nephrectomy renal arteriovenous fistulae, basing their remarks on the personal observation and 46 cases reported in the published literature. Surgical treatment is essential and consists, preferentially, of resection of the aneurysmal sac with dissection and a separate ligature of the artery and the vein. PMID- 6251560 TI - [ACTH response to 24 hours oral metyrapone test in normal children (author's transl)]. AB - A study of ACTH response to orally given metyrapone were carried out with 32 normal subjects aged 18 months to 15. Effectiveness of adrenal inhibition was supported by delta F > 5 microgram or cortisol level after metyrapone < 3 microgram/100 ml. The strong positive correlation between delta F and delta ACTH indicates the high sensibility of delta ACTH as an index of the responsiveness. No correlation was found between delta ACTH and weight, height, or age. Mean level (M +/- 2 SEM) are established: plasma ACTH level at 8 before metyrapone = 32,1 +/- 7,5 pg/ml; plasma ACTH level at 8 after metyrapone = 271,8 +/- 57 pg/ml; delta ACTH = 240 +/- 6 pg. Including these considerations, biological ACTH variability, and reproductibility of determinations, an abnormal response seems to be proved by plasma ACTH level at 8 after metyrapone < 100 pg/ml or/and delta ACTH < 70 pg. A normal response is established by delta ACTH > 150 pg. PMID- 6251561 TI - [Lack of ACTH responsiveness in children and paroxysmal central nervous system manifestations. (Study of nine cases of isolated ACTH deficiency) (author's transl)]. AB - Study of ACTH responsiveness to oral metyrapone and insulin hypoglycemia in children with repetitive nervous system manifestations (convulsions, coma, mental confusion apathy, tremor) has led to diagnosis of isolated ACTH deficiency in nine children within a three year period. Hypoglycemia was ascertained in five children; in four cases no hypoglycemia was proved, possibly because of promptly disappearance or because of other mechanisms accounting for clinical symptoms (occurrence of intracellular overhydratation associated with corticol deficiency is considered). The incidence of isolated ACTH deficiency in children is possibly undervalued. Reappraisal of isolated ACTH deficiency in childhood as to be considered in idiopathic spontaneous hypoglycemia and perhaps in some paroxysmal neurologic and/or digestive manifestations without proved hypoglycemia and so far poorly defined or held for epileptic fits. In order to disclose further additional tropic hormone deficiencies, and to differentiate permanent from transient impairment of ACTH responsiveness which often seems to be related to emotional deprivation syndrome, more protracted follow up studies are needed. PMID- 6251562 TI - [Cytological diagnosis of prostatic cancer by transrectal aspiration biopsy (author's transl)]. AB - From the cytologic study of fifty transrectal needle aspirations of the prostate the authors try to establish the principles leading to the diagnosis of prostatic carcinoma. Correlation with clinical diagnosis shows that in positive cases, cytologic diagnosis is accurate. In the case of negative cytologic responses this negative response may be imputable: to the paucicellularity of the sample, unavoidable blind needle aspiration, an early necrosis of the cellular material, a false interpretation of minimal cellular and nuclear abnormalities. This method proves valuable for the clinician. In two cases out of three the cytological diagnosis confirms the clinical diagnosis. PMID- 6251563 TI - [Inflammatory rheumatic disorders during the course of secondary syphilis (author's transl)]. AB - A 46-year-old man presented signs of secondary syphilis, including a skin eruption, multiple adenopathies, and alopecia. The diagnosis was confirmed by positive serological and Nelson's tests. Inflammatory arthritic signs developed in a few joints two weeks after the onset of the skin eruption, affecting mainly the left wrist, right sternoclavicular joint, lumbar spine, and right shoulder and hip joints, which were painful and stiff. Tests for a rheumatic origin, especially urethral smears and HLA B27 antigen, were negative. The articular manifestations disappeared completely after 8 to 10 days of penicillin. Rheumatic disorders from secondary syphilis affect one or several of the large joints, and quite frequently the sternoclavicular joints, the clinical, radiological, and biological characteristics showing no particular features. Diagnosis is based on the exclusion of other causes for the rheumatic disorder, total rapid regression after penicillin alone, and the simultaneous appearance of the affections. PMID- 6251564 TI - [Gastric tuberculosis, villous atrophy, dermatitis herpetiformis (author's transl)]. AB - A case of gastric tuberculosis associated with villous atrophy is reported in a sixty-three years old female. Fifteen years before she had a skin-disease whose histology was compatible with a dermatitis herpetiformis. Under treatment by gluten exclusion and anti-tuberculous drugs, a cure of gastric tuberculosis and a dramatic relapse of jejunal morphology were observed. PMID- 6251565 TI - [Two cases of ankylosing spondylitis in Negroes from Indian Ocean (author's transl)]. AB - Are reported: the first one, observed in Tananarive, on a 26 years old man born in Madagascar, with involvement of sacroiliac articulation and rachis. The second one, observed in Marseille on a 20 years old man who was born in la Reunion, with serious right coxitis and sacroileitis. In the second case, the investigation of HLA B27 antigen was positive. Both cases were probably primitive. A review of literature shows unusualness of ankylosing spondylitis in tropical countries. PMID- 6251566 TI - [Bronchial myoblastoma with cartilage injury (author's transl)]. AB - The authors present a new case of bronchial myoblastoma the particularity of which is the partial destruction of bronchial cartilages. This unusual aggressivity of the tumor facing the toughest bronchial structures does not seem to be an unfavourable prognosis element. Two years after resection, the tumor hasn't recurred. PMID- 6251567 TI - [Two new cases of the oculo-dento-digital syndrome (author's transl)]. AB - Authors report two new cases of oculo-dento-digital syndrome, besides the classical findings concerning the eyes, nose and upper extremities, they noted a relative shortening of the skeletal structure of the ocular maxillary region. This syndrome is thought to be an hereditary disease compatible with autosomal dominant inheritance. PMID- 6251568 TI - [Present data on inflammation. III. Experimentally induced inflammation (author's transl)]. AB - In a previous chapter, the importance of macrophages in inflammatory processes was emphasized upon. The authors now mention the outstanding inflammatory agents utilized for experimental purposes, especially as regards the pattern of their action. Finally, this paper restates the question of the pharmacology and therapy in inflammation. PMID- 6251569 TI - Acute immune hemolytic anemia in adults after cytomegalovirus infection. PMID- 6251570 TI - [Determination of blood serum 5'-nucleotidase activity in differential diagnosis of jaundice]. PMID- 6251571 TI - [Ultrastructural study of intra-erythrocyte inclusions in some haemolytic syndrome (author's transl)]. PMID- 6251572 TI - Radiation induced sarcoma. AB - A case of radiation induced sarcoma presenting seven years after radiotherapy for a conus cauda equina astrocytoma is reported. PMID- 6251573 TI - Comparative biochemical and ultrastructural studies of capillaries from normal humans, normal mice, and human cerebral astrocytomas. AB - Capillaries from cerebral white matter were isolated from normal humans and normal mice and from human astrocytomas (Grades II-IV) to investigate potential biochemical and ultrastructural differences between normal and neoplastic-derived microvessels. Capillaries from Grade III and IV astrocytomas averaged 55-fold higher in the concentration of total protein than capillaries from normal mouse and normal human cerebral tissues. Scanning electron microscopic examination revealed more bifurcations and fewer surface undulations in the capillaries derived from anaplastic astrocytomas than in capillaries derived from normal specimens. Sprouting configurations were detected in the capillaries from anaplastic astrocytomas. They measured 4 to 5 micron in diameter and manifested fewer surface undulations than capillaries from normal human white matter. The results of these preliminary investigations suggest early capillary growth from parent vessels in high-grade and highly vascularized astrocytomas. PMID- 6251575 TI - Plasma glucose monitoring during operation for insulinoma: a critical reappraisal. PMID- 6251574 TI - Stereotactic radiosurgery in Cushing's syndrome: acute radiation effects. AB - Stereotactic radiosurgery was used for selective destruction of adrenocorticotropic hormone (ACTH)-producing adenomas in 18 patients with Cushing's syndrome. A radiation-induced lesion in the most anterior part of the sella turcica caused remission of the disease. The acute increase in ACTH and cortisol secretion that occurred in the majority of patients had no predictable relationship to the final outcome. Decreased cortisol excretion during the first three weeks after treatment was positively correlated to favourable long-term results. The treatment is a therapeutic alternative to open selective excision of the adenoma. PMID- 6251576 TI - [Benign tumors of the scalp]. PMID- 6251577 TI - Ultrastructural observations on spermatozoa retained within the seminiferous epithelium after treatment with dibutyryl cyclic AMP. AB - Spermiation was inhibited in the Syrian hamster by administering large doses of dibutyryl cyclic AMP. After treatment with dibutyryl cyclic AMP most stage VIII, IX, and X seminiferous tubules contained some mature spermatozoa within the seminiferous epithelium. The acrosomal membranes and plasma membranes of the unreleased spermatozoa remained intact, indicating that the spermatozoa had not been phagocytized by the Sertoli cells. Sertoli-spermatid junctional specializations were usually applied to the heads of the mature spermatozoa. The unreleased spermatozoa often appeared swollen with accumulated fluid located in the subacrosomal space. The accumulation of subacrosomal fluid in the unreleased spermatozoa seems to result from the absence of tubulobulbar complexes. That is, when tubulobular complexes fail to form the normal flow of cytoplasm into the tubulobular complexes is blocked resulting in an accumulation of fluid around the nucleus. Inhibition of spermiation may result from the absence of tubulobulbar complex formation. It is postulated that the tubulobulbar complex functions to transfer a chemical trigger from the maturing spermatid into the Sertoli cell. This chemical trigger may initiate the disappearance of the Sertoli-spermatid junctional specialization and induce spermiation. PMID- 6251578 TI - [Neuropeptides, endorphins and psychoses]. PMID- 6251579 TI - [Diet and defecation]. PMID- 6251580 TI - [Investigations on combined injuries, 29th communication. Protective effect of aminopropylamino-ethylthiophosphate (WR 2721) in mice with radiation and combined injuries (irradiation and skin wound or burn) (author's transl)]. AB - Because of the crucial practical importance of combined injuries, investigations of the efficacy of the radioprotective agent aminopropylamino-ethylthiophosphate (WR 2721) were performed on mice which were whole-body X-irradiated and stressed with a second trauma either as an open wound or as burn wounds on the skin. In cases of sole whole-body irradiation, probit analyses of our data yielded the dose reduction factors (DRF) of 2.42 (NMRI-Hannover) and 2.12 (NMRI-Kisslegg). In case of a combination of an open skin wound (SW) with irradiation in mice of the Hannover breed the following dose reduction factors have been obtained: for irradiation+SDW 10 min p. r. the DRF 2.22, for irradiation+SW 2 d p. r. the DRF 2.30, and for irradiation+SW 8 d p. R.. the DRF 2.29. In cases of combined injuries with two burn wounds (BW) as second trauma in mice of the Kissblegg breed yielded: the DRF 2.01 for irradiation+BW 10 min p. r., and the DRF 1.91 for irradiation+BW 2 d p. r. The protective effect of WR 2721 is apparently similar in the various groups with combined injuries as compared to the animals exposed to whole-body irradiation only. The mechanisms of action of the sulphur containing radioprotective agents are discussed. PMID- 6251581 TI - Vitamin D3 sulfoconjugate in pregnant and lactating mother rats after dosing with 3H vitamin D3. AB - Twenty four hours after dosing of pregnant rats with 3H vitamin D3 i.v. the sulfoconjugate was detected only in the kidney. In contrast, 24 or 48 hours after 3H vitamin D3 i.v. dosing the vitamin D3 sulfoconjugate was detected in the plasma, liver, kidney and mammary glands of lactating mother rats. PMID- 6251582 TI - [Membrane-bound intranuclear inclusion bodies and their occurrence in Aujeszky's disease]. PMID- 6251583 TI - [Control of cell multiplication in vitro. II. Relationship between cell multiplication and cyclic AMP concentration]. AB - Compairing non-transformed mouse fibroblasts and some L-cell variants, it was shown that the decrease of dependence on serum mitogenic factors, and the decease of sensitivity to the contact inhibition of growth do not always correlate with the decrease of intracellular cAMP content. The decrease of sensitivity of transformed cells to the factors limiting non-transformed cell growth in vivo might be also connected with a relative independence of the cell growth on the intracellular level of a cAMP. PMID- 6251584 TI - [Relationship between the effect of dibutyryl-cAMP on L cell differentiation and cell population density]. PMID- 6251585 TI - [Effect of an industrial-frequency electromagnetic field on protein biosynthesic processes of embryonal fibroblasts in tissue culture]. AB - Using radioautography, the influence of the industrial frequency electromagnetic field (50 cps) (EMF i/f), with the tension of 50 and 150 kv/m was studied, on the synthesis of collagen and non-collagen proteins in cultured fibroblast-like human embryo cells in the presence and absense in the medium of adrenaline and of cyclic adenosine monophosphate (cAMP). The EMF depresses protein proportionally to its intesity and duration. The specific function of fibroblasts -- the synthesis of collagen -- is subject to this influence to a great extent. The preliminary administration of adrenaline or cAMP prevented the above changes. The cyclic AMP exerted a much stronger protective effect. PMID- 6251586 TI - Some virus diseases of domestic animals in the Sultanate of Oman. AB - Little is known of the occurrence of animal virus diseases in the Sultanate of Oman. This paper reports the results of a countrywide survey carried out in 1978 to establish the prevalence of some important viral pathogens of domestic animals with the dual purpose of providing baselines for future investigations and guidelines for those entrusted with disease control. Foot-and-mouth disease virus type O, previously identified in Oman in 1976, was isolated from clinically affected animals. In addition, virus types A and Asia 1 were isolated from unaffected animals. Serological studies indicated that infection with all 3 types had been widespread. The presence of infectious bovine rhinotracheitis was confirmed by virus isolations and sheep and goat pox, long recognised in Oman, was confirmed by the demonstration of pox particles in dried lesion material. In serological studies antibodies were found to the viruses of peste des petits ruminants, bovine herpes mammillitis, bovine virus diarrhoea, parainfluenza 3 and African horse sickness. There were no significant antibody levels to rinderpest in unvaccinated animals and no antibody to equine infectious anaemia or vesicular stomatitis viruses. PMID- 6251587 TI - Stability of characters of mammary tumors in BALB/cfRIII mice. AB - The biological and morphological characteristics of mammary tumors in BALB/c mice infected with RIII mammary tumor virus (MTV) by foster nursing have substantially kept stable and unchanged after 20 years, 53 inbred generations and transfer of the strain from Perugia to Pisa. This suggests that the causal MTV keeps unaltered in time its biological properties. PMID- 6251588 TI - Mullerian adenosarcoma of the uterus: a report of 5 cases. AB - The clinicopathologic features of 4 cases of Mullerian adenosarcoma of the uterine body and 1 of the cervix are reported. They showed the characteristic pattern of benign epithelial growth within sarcomatous stroma. In the cervical tumor, malignant heterologous stromal cells were also present. All the patients are alive and well, confirming the good prognosis of this neoplasm. The authors think that the presence of a malignant heterologous component probably does not imply a worse prognosis. PMID- 6251589 TI - Reactions to contrast material during retrograde pyelography. AB - Reactions to contrast material during retrograde pyelography are rare. Two cases are reported, and the literature is reviewed. PMID- 6251590 TI - [Results of using dexamethasone in treating experimental uveitis]. PMID- 6251591 TI - [Chemodectomas with an outlet into the parapharyngeal space and larynx]. PMID- 6251592 TI - Microbiology of the canine and feline eye. PMID- 6251593 TI - Primary corneal disease in the dog and cat. PMID- 6251594 TI - Biochemistry of the lens and cataractogenesis: current concepts. PMID- 6251595 TI - Current concepts in veterinary neuro-ophthalmology. PMID- 6251596 TI - Infectious bovine rhinotracheitis vaccine. PMID- 6251598 TI - Myofibroblasts and myoepithelial cells in human breast carcinoma. An ultrastructural study. PMID- 6251597 TI - [Comparative studies of sera from cattle with complete leukemia virus and glycoprotein antigens]. AB - One hundred cattle serums were investigated by the AGTD-test with two antigens: an antigen produced by the whole virus and an antigen containing glycoproteins. Of all serums studied 44 showed a specific precipitation in case the glycoprotein antigen was used. In case the antigen from the whole virus was used 41 serums showed a specific precipitation line, while in 3 of the serums two precipitation lines were observed. Fifty six serums proved negative, containing no antibodies against bovine leucosis virus, after antigens were used. In 2 of the serums non specific precipitation lines were obtained when the antigen from whole virus was used. the precipitation lines produced by both antigenes did not differ in intensity and time of manifestation. PMID- 6251599 TI - Herpesvirus-associated nuclear antigen(s) in cells biochemically transformed by fragments of herpesvirus DNA and in somatic cell hybrids. PMID- 6251600 TI - Replication and assembly of VSV nucleocapsids: protein association with RNPs and the effects of cycloheximide on replication. PMID- 6251601 TI - Novobiocin blocks the shutoff of SPO1 early transcription. AB - Novobiocin, an inhibitor of bacterial DNA gyrase strongly impairs the development of bacteriophage SPOl. DNA replication seems to be the primary target for the antibiotic in this system, but viral-coded transcription is also affected in several aspects: (a) The level of phage transcription is diminished; (b) the shutoff of the synthesis of early RNA classes is inhibited; (c) RNAs of late class are not synthesized. This last effect is a consequence of the coupling between transcription and replication. The other two results could be taken as an indication that the appropriate secondary structure of the parental phage DNA is a requisite for the recognition of promoters. The introduction of negative turns by DNA gyrase seems to make early genes unavailable for transcription. PMID- 6251602 TI - Isolation and partial characterization of a 55,000-dalton protein induced in cells transformed by the ml strain of Moloney murine sarcoma virus. PMID- 6251603 TI - Resistance of herpes simplex virus to acycloguanosine--genetic and physical analysis. PMID- 6251604 TI - Correlation of the genetic and physical maps in the central region of the bacteriophage Mu genome. PMID- 6251605 TI - Localization and organization of integrated simian virus 40 sequences in a human cell line. PMID- 6251606 TI - DNA of a chicken herpesvirus is associated with at least two chromosomes in a chicken lymphoblastoid cell line. PMID- 6251607 TI - In ovo tumorigenesis induced by avian osteopetrosis virus. PMID- 6251608 TI - Polypeptides of feline leukemia virus: a glycosylated gag-related protein is released into culture fluids. PMID- 6251609 TI - Identification of proteins tightly bound to herpes simplex virus DNA. PMID- 6251610 TI - A map of the late proteins of vaccinia virus. PMID- 6251611 TI - Poly(A)-adjacent sequence of the 14.5 S mRNA of vesicular stomatitis virus (New Jersey serotype). PMID- 6251612 TI - The translation products of Moloney murine sarcoma virus-124 RNA. PMID- 6251613 TI - Recovered src genes are polymorphic and contain host markers. PMID- 6251614 TI - Effect of arildone on modifications of poliovirus in vitro. PMID- 6251615 TI - Replication of flaviviruses: separation of membrane translation sites of Kunjin virus proteins and of cell proteins. PMID- 6251616 TI - Inhibition of animal virus production by means of translation inhibitors unable to penetrate normal cells. PMID- 6251617 TI - Isolation and polypeptide characterization of varicella-zoster virus. PMID- 6251618 TI - Gene order of murine mammary tumor virus gag proteins and env proteins. PMID- 6251619 TI - Isolatin and characterization of a viable deletion mutant of adenovirus type 3. PMID- 6251620 TI - Intramembrane structural differentiation in Sendai virus maturation. PMID- 6251621 TI - Synthesis of chromosomal proteins and Epstein-Barr virus DNA in activated Burkitt somatic cell hybrids. PMID- 6251622 TI - Genetics of bacteriophage P22. III. The late operon. PMID- 6251623 TI - Genetics of bacteriophage P22. IV. Correlation of genetic and physical map using translocatable drug-resistance elements. PMID- 6251624 TI - [Pyrophosphate scintigraphy of the myocardium after cardioversion]. PMID- 6251625 TI - [Status of research on physical and health resort therapy in nervous system diseases]. PMID- 6251626 TI - [Cyclic nucleotide system and the hormone content in allergic dermatoses in children]. PMID- 6251627 TI - [Enzymatic activity in the blood serum in mixed viral hepatitis]. PMID- 6251628 TI - [Activity of malate dehydrogenase, cytochrome oxidase and their isoenzymes in the blood serum in chronic cor pulmonale]. PMID- 6251629 TI - [Comparative results from the use of the direct immunoperoxidase and immunofluorescence methods to diagnose chronic herpetic infection]. AB - Comparative data are presented on application of varying methods for viremia detection in hamsters with chronic herpesvirus infection (CHVI). The specificity of the immunofluorescent method was shown in a comparative diagnosis of CHVI when virologic and immunomorphologic methods was used. At the same time the immunoperoxidatic method proved more advantageous because it is specific, simple and realizable in common laboratory conditions, and the preparations can be preserved for a long time. PMID- 6251630 TI - [Hepatitis viruses in tissue culture]. PMID- 6251631 TI - [Biophysical parameters and biological activity of Herpes simplex DNA. Restriction analysis]. PMID- 6251632 TI - [Dispersion analysis of viral suspensions by the technic of optical mixing spectroscopy]. AB - To evaluate the heterogeneity of virus populations and determinations of virus monoparticle size in suspensions, a dispersion analysis by the method of spectroscopy of optic mixing was developed. The parameters of influenza USSR/Khabarovsk and parainfluenza Sendai virus suspensions were measured in correlation spectrometer and the results were computerized. PMID- 6251634 TI - [Comparative analysis of the dynamics of antibodies to influenza A (H1N1) and A/Hong Kong/1/68 (H3N2) in the sera of a healthy population]. AB - A comparative analysis of the dynamics of antibodies against A(H1N1) and A/Hong Kong/I/68 (H3N2) influenza viruses was carried out in the blood sera of healthy population in some cities of the USSR. The data obtained suggest that anamnestic antibody production can be stimulated only by the drift- and not by the shift variants of viruses, i.e. by those with varying hemagglutinin serotypes. PMID- 6251633 TI - [Isolation of influenza virus from Chlidonias nigra and serologic examination of the birds for antibodies to influenza virus]. AB - Influenza A virus with the antigenic formulae Hav4Neq2 has been isolated from Chlidonias nigra in the region of mass moulting in the territory of the Kazakh SSR. Antihemagglutinins for the newly isolated virus were detected in the sera of some specimens of the sea gull order. The data obtained suggest an active circulation of the virus in this region during the summer of 1977. PMID- 6251635 TI - [Detection of antigens immunologically related to the envelope antigens of mouse mammary gland cancer virus antigens in human breast cancer tissue]. AB - A highly sensitive method of electroimmunodiffusion in acetate cellulose films developed by G.I. Abelev on the principle of isotachophoresis was used for the detection in human mammary gland carcinoma (HMGC) of an antigen related to envelope antigens of mouse mammary gland cancer (MMGC) virus. In 4 out of 10 HMGC cases, fractions of proteins with molecular weight about 50,000 d previously isolated in PAAG with sodium dodecyl sulphate were found to contain an antigen reacting with the antiserum to p52 MMGCV precipitation band which proved immunological identity of both antigens. PMID- 6251636 TI - ["Pharaoh" line culture of Japanese quail cells as a leukosis-free system for virus reproduction]. AB - Contamination of Japanese quail, strain Pharaoh, cell culture with oncogenous and infectious avian viruses was studied. The susceptibility of the embryonal cell cultures of the Japanese quail, strain Pharaoh, to measles, parotitis and fixed rabies viruses was also determined. It was found that the sera of pubertal quails had no antibody to Rous sarcoma virus (RSV), strains Brian, RSV (RAV-1), Schmidt Ruppin, Carr-Zilber, as well as to Marek's disease and Newcastle disease viruses. No reverse transcriptase activity was detected in the embryonal alantoic fluid of this avian species. The quails were less susceptible, as compared to the chicken, to Schmidt-Ruppin and Carr-Zilber strains of RSV. Measles, parotitis and fixed rabies viruses reproduced actively in the Japanese quail, Pharaoh strain, embryonal cell cultures. It is suggested that the embryonal cell cultures of this avian species can be used as a leukemia-free substrate for experimental studies and manufacturing of viral vaccines. PMID- 6251637 TI - [Serum magnesium and the elimination of cyclic adenosine monophosphate in the urine in chronic kidney insufficiency]. PMID- 6251639 TI - Fanconi syndrome and oat cell carcinoma of the lung. PMID- 6251638 TI - [Potentials of complex radionuclide study of the joints in the diagnosis of osteoarthrosis]. AB - The possibilities of the complex radionucleid joint investigations in the diagnosis of ostheoarthrosis are discussed. The investigation covered 104 patients with osteoarthrosis, aged 471 +/- 2.0 and 22 control subjects, aged 43.9 +/- 3.1. The time for half-elimination of 133Xenon injected in the knee joint is 154.8 minutes for the healthy subjects and 122.2 minutes for those suspected of narrowing of the joint cavity resp., 105.4 minutes for the patients with II X-ray stage and 77.7 minutes for III-IV X-ray stage of osteoporosis. The accumulation of 99MTc-pertechnetate is 115.3 per cent for the control group and 134.9 per cent, 127.7 per cent and 143.0 per cent for the patients with I, II and III-IV X ray stage of osteoarthrosis. The accumulation of 99MTc-pyrophosphate is 115.7 per cent in the sound joints and 144.8 per cent; 158.1 per cent and 170.7 per cent resp., according to X-ray stage of the diseases. With the progress of bonetissue destruction the effektiveness of Xenon clearance is improved as well as of 99MTc pyrophosphate in the joints investigated. High reactivity of joint structure (synovial membrane and bone epiphysis) was established in the early and late stages of osteoarthrosis. The radionucleid constellation of an intensified joint clearance, high pyrophosphate test and light fluctuating pertechnetate joint index are indicative for a diagnostic test of the disease prior to the manifestation of confirmed X-ray data. Catabolic osseous destruction is coordinated, according to rate, with the effectiveness of the j oint 133Xenon clearance and with the accumulation of 99MTc-pyrophosphate in the joints with arthrosis alterations. PMID- 6251640 TI - Healing and control of healing. PMID- 6251641 TI - Collagenolysis: the other side of the equation. PMID- 6251642 TI - [The bioptical exploration of non-tuberculous cavities in the lungs]. AB - Considering the difficulties in X-ray differentiating, every lung abscess should be submitted to a bronchologic-bioptical control. In using the fine needle biopsy for the cytological evaluation, no severe complications could be observed so far. A promising therapy of the lung abscess is given by perthoracal local treatment. PMID- 6251643 TI - [Biopsy of suspected metastatic lung lesions]. AB - Among the tumours of the lung metastatic formations are to be expected in 7.5 to 10% of the cases. This is based on the anamnesis, on the X-ray findings or on the results from bioptical examinations. Compared with primary tumours, cytological investigations of the exfoliative material are less effective (positive results in about 50% of the cases). As metastatic formations primarily manifest themselves in the interstitium and only late touch the bronchial system, direct excision of material or methods of puncture respectively are from the first much more promising. Sixty out of 95 patients with pulmonary processes, supposed to show metastatic formations, had been submitted to a bioptical control, mainly by means of fine needle biopsy, with the following cytological evaluation of the material. In 50 cases it was possible to secure the finding morphologically, i.e. in 83.3% of the cases. The cytological appearance, too, leads to a clear position to the primary tumour, for example in hypernephroid carcinomas, pigment-storing melanomas, diseases of the lymphatic system and various sarcomas. PMID- 6251644 TI - [Value of disodium cromoglycate (INTAL) in the treatment of obstructive pulmonary diseases (author's transl)]. AB - Disodium cromoglycate has a strong place in the differentiated treatment of asthma. Especially the use is indicated in extrinsic asthma, but trials of treatment are also indicated in other kinds of asthma. It is reported about the present ideas of pharmacodynamics. Own results of examinations in an open study of 15 patients and a crossed double-blind-study of 40 patients are discussed. PMID- 6251645 TI - [Progressive coordinate structuring (target-tree method) in studying problems of dispensary care for selected groups of the population]. PMID- 6251646 TI - [Effect of cytochrome C and zinc ions on acid-base metabolism in burn shock]. AB - The authors investigated the influence of cytochrome C and zinc ion on the acid base balance in experimental burn shock (animal experiments in rabbits). A pH value stabilisation was obtained in the first shock hours after a single injection of cytochrome C and also after a single injection of zinc ion in another rabbit group. PMID- 6251647 TI - [Phosphatases and oxidative enzymes in the kidney of the Prussian carp (Carassius auratus gibelio Bloch) adapted to salt water]. AB - The distribution and activities of phosphatases and oxidative enzymes have been determined with the help of histochemical methods in the kidney of the Prussian Carp, a stenohaline freshwater-fish. In addition to fish maintained in freshwater aquaria, a group of the animals used has been adapted to seawater of moderate salinity. The following pattern of enzyme reaction intensities has been observed in the various kidney structures: Strong reactions of alkaline phosphatase in the nephron are confined to the glomerular capillary convolute and the brush border of proximal segments. Equally enzyme activities are observed in the connective tissue sheath of the collecting duct -- archinephric duct system. Acid phosphatase can be detected in all segments of the nephronic tubule, strong activities are found in the proximal segment (P I), in the epithelium of the archinephric duct, and, especially, in the interstitial tissue. ATPase reacts strongly positive in epithelial cells of the distal tubule and the collecting duct -- archinephric duct system. ATPase reactions are inhibited by Ouabain, and therefore can be regarded as reactions of Na--K-ATPase. Mitochondrially bound oxidative enzymes, connected with the citric acid cycle and the respiratory chain, show very strong reaction intensities in the distal tubule and the collecting duct- archinephric duct system, while the glomeruli generally exhibit negative reactions. Lactate -- and malate dehydrogenases are found to react weakly to negatively throughout the whole kidney. Maintenance in seawater does not deeply affect the enzyme pattern of the kidney of the Prussian carp, with exception of some oxidative enzymes, reacting weaker in the distal tubule and the collecting duct-archinephric duct system. In addition, the epithelial cells of the archinephric duct of seawater adapted fish show a marked apical localization of reaction products for these enzymes. Possible relations between enzyme histochemistry and fish kidney physiology are discussed, in connection with comparative aspects of the enzyme histochemistry of the vertebrate kidney. A short review of normal histology and function of the kidney of the Prussian carp is added. PMID- 6251648 TI - A histochemical study on the adrenal components of the teleost Cirrhinus mrigala (Ham.). AB - The adrenal components of C. mrigala are embedded in the pronephric cephalic kidney around the post cardinal vein. The cortical cells responded positively to the lipids, ascorbic acid, delta 5-3 beta-HSD, G-6-PD, MAO, acid and alkaline phosphatase tests. The presence of intense MAO activity may suggest the possible involvement of monoamines in the adrenocortical function. Localization of lipids and delta 5-3 beta-HSD show the sites of corticosteroid synthesis. In the chromaffin cells, MAO, acid and alkaline phosphatase activity was moderate whereas they gave a strong reaction to ascorbic acid test in comparison to the cortical cells. Noradrenaline (NA) and adrenaline (A) storing cells were differentiated adopting glutaraldehyde silver, dichromate and iodate techniques. NA and A storing cells are almost totally depleted of their contents after reserpine treatment. The histochemical response of the adrenal gland of this species is largely comparable to that of higher vertebrates. PMID- 6251649 TI - [The difficult way back. On integration of mental patients following dehospitalization--a psychodemoscopic study on opinion of the general public and the patient]. PMID- 6251650 TI - [Breast cancer and melanoma in progressive scleroderma]. PMID- 6251651 TI - [Ambulatory care of suicide-prone patients in hospital and office setting]. PMID- 6251652 TI - [Protein specificity as the basis of the molecular organization of the integrative activity of the nervous system]. PMID- 6251653 TI - [Morphofunctional mechanisms of regulating impulse conduction and the formation of functional systems of neurons in the CNS]. PMID- 6251654 TI - [Central mechanisms controlling pain sensitivity]. PMID- 6251655 TI - [Problem of specific initiation during replication and transcription of the genomes of RNA-containing viruses]. PMID- 6251657 TI - [Pituitary adrenocorticotropic hormone in the regulation of the cardiovascular system]. PMID- 6251656 TI - [Antibody affinity]. PMID- 6251658 TI - [Hormones, their mechanism of action and the regulation of metabolism]. PMID- 6251659 TI - [Achievements in the field of the surgical treatment of endocrine disease patients]. PMID- 6251661 TI - [Biosynthetic and metabolic pathways and the mechanism of action of thyroid gland hormones normally and in pathology]. PMID- 6251660 TI - [Problems of the synthesis and study of neurohormones]. PMID- 6251663 TI - Instestinal obstruction as a late complication in rotentgen therapy of Wilms' tumor. AB - A case of intestinal obstruction, as a result of radiation injury of the colon, is reported. This child was treated by roentgen therapy in the infant period because of a Wilms' tumour of the left kidney. PMID- 6251662 TI - [Results and prospects in the study of peptide and protein hormones]. PMID- 6251664 TI - [The use of 99mTc-pyrophosphate indices in the quantitative evaluation of rheumatoid arthritis activity]. AB - The authors have presented their own method of defining "joint to bone" and "joint to joint" radioactivity indicators with the application of 99mTc pyrophosphate. Investigations of the degree of 99mTc-pyrophosphate accumulation in the 4 chosen points have shown that the lowest coefficient of changeability points out at half of crus length. The authors have employed radioactivity measurement of this place as a constant reference point while defining all the indicators "joint to bone". On the basis of the investigations carried out in 45 patients with varied degrees of rheumatoid arthritis activity and in the control group of twenty individuals it was established that the applied method makes possible the quantitative evaluation of rheumatoid arthritis activity in a simple way and in a short time. PMID- 6251665 TI - [Concomitant diseases in acromegaly and endocrine inactive pituitary adenomas. A morphological study of 65 cases (author's transl)]. PMID- 6251666 TI - [True congenital nephroblastoma (author's transl)]. AB - A case of true congenital nephroblastoma is reported. The macroscopic and histologic features of this extremely rare renal lesion are depicted in detail and compared with those of congenital mesoblastic nephroma (fetal mesenchymal hamartoma). PMID- 6251667 TI - [Quantitative histological observations in gliomas (author's transl)]. AB - 30 autopsy cases of gliomas (5 fusiform glioblastomas, 5 multiform glioblastomas, 5 fibrillary astrocytomas, 5 protoplasmic astrocytomas, 5 oligodendrogliomas, 5 spongioblastomas) were studied by means of morphometry. 7 parameters (volume and area parameters of tumor vessels and of tumor cell nuclei, mitoses) were tested for the ascertainament of useful quantitative criteria for the objective differentiation of the gliomas. 210 statistical comparisons were carried out. Significant differences were observed in 32 of them. It could be demonstrated that the parameters of the tumor cell nuclei are most useful in the differentiation of the gliomas. Significant differences do not exist between fusiform glioblastoma--multiform glioblastoma, fusiform glioblastoma- oligodendroglioma, fibrillary and protoplasmic astrocytoma--spongioblastoma. PMID- 6251668 TI - [Benign fibrous histiocytoma of bone (author's transl)]. AB - A case report is presented of a large cystic lesion of the proximal end of the left femur in a 66 years old man which is classified as a benign fibrous histiocytoma of bone. After the first description of the malignant fibrous histiocytoma of bone in 1972, this is the first report of the benign type of this tumor. PMID- 6251669 TI - [Rate tumour types in scars of the lung (author's transl)]. AB - A report is given on three rare tumor types that developed in chronic lung scars. There were a malignant mucoepidermoid tumor, a carcinosarcoma, and a mixed tumor consisting of a carcinomatous and a mesenchymal part. The scar is regarded as the realizing factor in these tumors. PMID- 6251670 TI - [Prophylaxis of gallstone formation (author's transl)]. AB - Today we know the pathobiochemical mechanism of gallstone formation. Cholecystectomy is the therapy of choice with a mortality-rate 0,5% in uncomplicated cases. The mortality-rate increases in patients with recurrent stones in the biliary tract system after cholecystectomy. In addition the liver produces a lithogenic bile. We propose the prophylactic use of chenodesocycholic acid in patients after choledochal revision, if the bile duct system is altered in such a way that cholesterol crystals can aggregate and grow to stones. A low dose of cheno acid is sufficient. Moreover a fibre rich diet increases the chenodesoxycholic acid synthesis in the liver. PMID- 6251671 TI - [Neurogenic tumours: clinical and therapeutic aspects (author's transl)]. AB - Tumours of the nervous system are rare. Clinical and therapeutic aspects are discussed with relation to 54 cases. The benign tumours of the peripheric nerves such as neurinomas and neurofibromas, show a high rate of malignant degeneration. For this reason, every tumour of the soft tissues has to be removed and should be examined by the pathologist. In cases of retroperitoneal and intestinal localisation an early diagnosis is frequently impossible. For differential diagnosis laparotomy or thoracotomy are always indicated. X-ray examinations of the kidneys, the thorax as well as the intestines and mesenteric vessels show satisfactory results. The neurogenic sarcomas and neuroblastomas are discovered late because of their hidden localisation and poor symptoms. The poor prognosis has not been improved by cytostatsis and radiation. PMID- 6251672 TI - Enteroviruses in drinking water correlated with the physical-chemical and bacteriological indicators of water quality. AB - A comparison between the presence of enteroviruses and the physical-chemical and bacteriological qualities of drinking water showed that the usual treatment procedures of surface water, though correctly applied to satisfy the standards of quality, yet failed to achieve complete removal of enteroviruses. Thus the results obtained in field conditions confirmed the data established experimentally in laboratory conditions, by other authors. PMID- 6251673 TI - Studies on the pathogenesis of Aleutian disease of mink. X. Demonstration of immune complexes by the 125I-C 1 q binding test after experimental infection. PMID- 6251674 TI - Detection of precipitating antibodies and identification of bovine leukemia virus antigens by micro counter-current immunoelectrophoresis. PMID- 6251676 TI - [Electron microscopic findings on reversion of Listeria L-forms]. AB - Reversion in L-forms of Listeria monocytogenes was studied with the use of electron microscopy. In the culture undergoing the process of reversion cells differing in size, form and the electron density of the cytoplasm were present. The process of reversion was characterized by the increase of cytoplasmic density, the decrease of nucleoid, the appearance of fibrillary material of medium electron density on the membrane surface and the longitudinal elongation of the cell. The cell wall of the revertants was thinner and its outer layer with greater electron density was less pronounced than in the initial culture. PMID- 6251675 TI - [Localization of oxidative enzymes of bacteria by means of electron microscopic cytochemistry]. PMID- 6251677 TI - [Biological characteristics of coagulase-negative staphylococci isolated from conjunctivitis]. AB - The biological properties of 101 strains of coagulase-negative staphylococci isolated from conjunctival secretions of conjunctivitis patients, as well as from healthy persons were studied. More than a half of these strains (66%) were identified as Staph. epidermidis. 18% of the strains differed from this species only by the absence of phosphatase activity. The existence of the phosphatase negative variants of Staph. epidermidis was inferred from this fact. About 1/3 of the cultures could not be identified in accordance with the scheme of the International Subcommittee on the Taxonomy of Staphylococci and Micrococci. The biological activity of the cultures isolated from conjunctivitis patients did not differ from that of the cultures isolated from healthy persons. The frequent occurrence of hemolytic activity in the strains isolated from both conjunctivitis patients and healthy persons was noted (88% and 83%, respectively). The conclusion on the variegated character and lability of the phenotypic characteristics of staphylococci has been made. PMID- 6251678 TI - [Effect of different doses of diphtheria exotoxin on the properties of L929 and HeLa cells]. AB - Various forms of interaction between diphtheria exotoxin and the continuous L and HeLa cell lines were revealed, depending on its doses: toxic, subtoxic and small (following the subtoxic dose). Cells of the same origin, treated with these doses, develop similar changes in some of their properties, differing only in their "survival" time, the period of adaptation and the time of entering the phase of active proliferation. the systems of cells, having simultaneously low susceptibility to infection with some RNA-containing viruses (L cells with low susceptibility to vesicular stomatitis virus and HeLa cells with low susceptibility to Coxsackie B5 virus) and high susceptibility to repeated treatment with diphtheria exotoxin, have been obtained. PMID- 6251679 TI - [Genetics of immunoglobulins]. PMID- 6251680 TI - [Bordetella pertussis bacteriophage]. AB - For the first time Bordetella pertussis bacteriophage was isolated, and its presence was confirmed by electron microscopy and by agar layer titration. The lysogenic strains were activated by their treatment with mitomycin C in a dose of 4.5 mg/ml. The phage system of the Bordetella genus, heretofore unknown, has been revealed: Bordetella pertussis phage lyzed all the tested strains of Bordetella parapertussis (25 strains) and could be passaged in these strains. The phage formed turbid and transparent negative colonies 0.1 mm and 0.15 mm in size. The phage titer (e. g., in strain No. 3865) was 1 X 10(10). The lysogenic variants of Bordetella pertussis, capable of spontaneous release of the phage, were obtained. These variants were characterized by changes in some of their phenotypical properties, e.g., the increased content of certain toxic substances and increased virulence. PMID- 6251682 TI - [Analgesic cutaneous electrostimulation in diseases of the nervous system (technic and indications)]. AB - In 76 patients with various pathologies of the nervous system accompanied with the pain syndrome, cutaneous electric stimulation was used for analgesia. The optimal effect was attained by proper positioning of the electrodes, use (as usual) of the monopolar method of the stimulation simultaneously in two sites, and maintenance of the definite parameters of the electric current (rectangular impulse duration 0.1 to 0.2 msec, frequency 60 to 70 o. p. s., current strengh 30 to 50 mA). A prolonged analgesic effect depended little on the disease entity: it was the duration of the pain syndrome that was the main factor predetermining the degree of the analgesic effect. PMID- 6251681 TI - [Metabolism of lipid peroxidation products in multiple sclerosis patients]. AB - Concentration of dienic conjugates and malonic dialdehyde (metabolites of lipid peroxidation) were examined in the blood and the cerebrospinal liquor of patients suffering from disseminated sclerosis, CNS tumours complicated with neurological pathology, and osteochondrosis with the secondary radical syndrome at D4--D5 and D5--S1 levels. In patients with disseminated sclerosis no malonic dialdehyde was found in the cerebrospinal liquor, while its blood level exceeded normal 1.5 to 2 times. After hormonal therapy the situation was found to be reverse: malonic dialdehyde appeared in the cerebrospinal liquor, while its serum level dropped. This is, probably, due to a stabilization of the process and a fall of the concentrations of antioxidants in the liquor. An experiment with direct determination of the antioxidant activity in the liquor confirmed the hypothesis on migration of antioxidants from myelin to the liquor during process exacerbation. Since in cases of CNS tumours (contrary to disseminated sclerosis) malonic dialdehyde is regularly present in the cerebrospinal liquor, a test is suggested for diagnostic differentiation between atypic forms of disseminated sclerosis and CNS tumours. PMID- 6251683 TI - Metastatic malignant fibrous histiocytoma in lung examined by fine needle aspiration: case report and literature review. AB - Malignant fibrous histiocytoma appears to be emerging as one of the most common soft tissue sarcomas of late adult life. Cytologic features of a metastatic malignant fibrous histiocytoma in the lung, examined by fine needle aspiration, are reported. Essentially, four cell types in various proportions were observed: spindled cells, pleomorphic giant cells, undifferentiated mesenchymal-type cells and rare signet ring "lipoblast-like" cells. There also were several huge hyperchromatic and often bizarre naked nuclei. PMID- 6251684 TI - Cytologic features of a mixed mesodermal tumor of the uterus demonstrated by cells obtained with the mi-mark endometrial sampler. AB - A case is reported of a 68-year-old woman with a malignant mixed mesodermal tumor of the uterus. Prior to diagnostic curettage and hysterectomy, cells were obtained with the Mi-Mark Endometrial Sampler. Cellular features are described in detail. PMID- 6251685 TI - 46, XY lung adenocarcinoma in a 46, XX female patient. PMID- 6251686 TI - Influence of corticotrophin on plasma testosterone in normal women. AB - The concentrations of ACTH and testosterone (T) in the plasma from 12 normal women (aged 18-35 years) were simultaneously determined at various times after im injection of 1 mg corticotrophin. The increase in the plasma level of total immunoreactive ACTH was maximal 0.5 h after the injection (mean value 1123 as compared to 36 pg/ml in the basal state); at 48 h, the ACTH level was still 2.4 fold that measured in the basal state. The administration of corticotrophin induced a broad increase in the mean level of plasma T which was highly significant (P < 0.001) at 4, 6, 8, 16 and 24 h after the injection. The maximum T response was detected at 16 h (mean value 477 as compared to 338 pg/ml in the basal state). The results indicate that plasma T is susceptible to stimulation by a pharmacological dose of ACTH in normal women. This effect should be taken into account in evaluating the indication of ACTH as a therapeutic agent. PMID- 6251687 TI - Effects of angiotensin I converting enzyme inhibitor (SQ 14225) on control of aldosterone. PMID- 6251688 TI - Improved sensitivity to adrenocorticotrophin after purification and pre incubation of isolated rat adrenal cells. PMID- 6251689 TI - The effect of bromocriptine during early pregnancy in the rat: inhibition of implantation. AB - The increase in the number of the ovarian LH/hCG-receptors and of serum progesterone concentration during pregnancy in the rat is highly dependent on the presence of prolactin during the luteinization process. Blocking of the hypophyseal prolactin secretion by twice daily injections of 2 microgram/g body weight bromocriptine into rats from the first day of pregnancy onwards prevents the increase in ovarian hCG-binding and progesterone production. Similar results are obtained by application of bromocriptine during the first three days only or either at day 1, 3 or 5 after mating. In all bromocriptine treated rats implantation of blastocysts does not occur. The failure to implant is not due to a teratogenic effect of bromocriptine onto preimplantation embryos, but is probably the consequence of changes of the uterine mucosa caused by the lack of progesterone production in the luteal cells. PMID- 6251690 TI - Additional data from two kindreds with genetically induced deficiencies of erythrocyte pyrimidine nucleotidase. AB - Two subjects, not previously reported in detail, had severe inherited deficiencies of erythrocyte pyrimidine nucleotidase. This was manifested hematologically by moderate hemolytic anemia with splenomegaly, morphologically by punctate basophilic stippling of Wright's stained erythrocytes, and biochemically by intraerythrocytic accumulation of pyrimidine nucleotides, elevated concentrations of reduced glutathione, and partial deficiencies of ribosephosphate pyrophosphokinase. All 5 of their children were asymptomatic and phenotypically normal except for intermediate reductions in activities of pyrimidine nucleotidase consistent with heterozygosity for an autosomal recessive defect. PMID- 6251691 TI - [Distribution and activities of enzymes in humeral epiphyses of albino rats of a specific age]. AB - In the cartilage epiphysis of newborn, 8-, 30-, and 60-day-old Sporague-Dawley rats, 5'-nucleotidase, adenosine triphosphatase, alkaline and acid phosphatase activities were found. The main centre of activity of nearly all enzyme reactions is situated, with only small temporal differences in animals of all age groups in the middle and distal cells of the column cartilage, the proximal hypertrophic cells and the chondrocytes of the opening zone. The cells of the tangential layer in the articular cartilage of newborn and 8-day-old rats demonstrate 5' nucleotidase activity. PMID- 6251692 TI - Comparative histochemical localization of some hydrolytic enzymes in mammalian epididymides. AB - The activity of enzymes hydrolyzing sodium-beta-glycerophosphate, adenosine triphosphate, adenosine monophosphate, and glucose-6-phosphate in the epididymides of adult ram, rabbit, rat and hamster has been investigated histochemically. The enzymes hydrolyzing sodium-beta-glycerophosphate, adenosine triphosphate and adenosine monophosphate were rather similar in their distribution in the intertubular connective tissue of the epididymides of the four species studied. However, the distribution and activity of these enzymes in the stereocilia varied. There was a high activity in the stereocilia of the middle segments of ram, rabbit and rat and in the proximal part of the terminal segment of hamster epididymides. Glucose-6-phosphatase was distributed homogeneously in the epithelial cells of the epididymides throughout the duct. The possible functions of these enzymes in the mammalian epididymis are briefly discussed. PMID- 6251693 TI - Further observations on peripheral neuropathy in the Syrian hamster with hind leg paralysis. AB - Pathological alteration of peripheral nerves in the mutant Syrian hamster with hind-leg paralysis were examined under the electron microscope. The changes included alteration of axonal caliber and abnormal distribution of axoplasmic contents. In addition, changes at the inner loop: axonal interface were noted which included accumulation of filamentous and granular material in the axon, loss of the inner loop membrane, and discontinuity of the subjecent axonal membrane. Demyelination and onion bulb formation was seen in the older hamsters. PMID- 6251694 TI - Intracytoplasmic inclusions (Bunina bodies) in amyotrophic lateral sclerosis. AB - In an autopsy case of sporadic amyotrophic lateral sclerosis, there were intracytoplasmic eosinophilic inclusions of the Bunina type in motor neurons. Electron microscopically, these bodies were observed as amorphous substances, irregularly deposited around the endoplasmic reticulum to form masses. Similar small masses were also visible in mitochondria. These substances did not stain for acid phosphatase. By analytical electron microscopy they contained silicon. Bunina bodies, therefore, seem to be due to deposition of some metabolite, but their nature is still obscure. PMID- 6251695 TI - Ultrastructure of adenoid cystic carcinoma arising in the salivary gland of a child. AB - A case of adenoid cystic carcinoma which developed in the left parotid gland of an 11-year-old girl was studied by electron microscopy. Islands of tumor cells, showing glandular and cribriform appearances, infiltrated the surrounding tissue and nerves. True lumina and pseudocysts were present in the islands of tumor cells. Electron microscopic examination revealed two types of tumor cells; clear cells (secretory epithelial cells) and dark cells myoepitheium-like cells). Some of the tumor cells, showing a transitional form between the two types, formed a part of the luminal wall. There were many crystalline spicules, cellular debris, and fine stellate granules in the lumina. Pseudocysts were composed of replicated basal laminae, fine stellate granules, and a central core of microfilaments. Rarely, a capillary was noted in the center of the pseudocysts. It is speculated that ultrastrutural features of adenoid cystic carcinoma in chidren may differ from the adult cases in the following ways; they contain numerous crystalline spicules in the lumina, dark cells with microvilli forming the luminal wall, and fine capillaries in the pseudocysts. PMID- 6251696 TI - Watery diarrhea, hypokalemia and achlorhydria syndrome. Morphological and immunohistological study. AB - A case of WDHA syndrome accompanied by a pancreatic tumor in a 44-year-old Japanese male is presented, the 6th case in Japan. Clinically, the patient suffered from unremitting watery diarrhea, hypokalemia and achlorhydria with marked anemia and jaundice. The patient died of emaciation, dehydration and bronchopenumonia, and an autopsy was performed. Autopsy examination revealed a hen's egg-sized tumor in the tail of the pancreas with metastases in liver, lungs and lymph nodes. In addition, bronchopneumonia and diabetic nephrosclerosis were present. Histologically, the tumor had the characteristics of an islet cell tumor, and histochemically the tumor cells were positive to Grimelius' stain which revealed non-B-islet cell features. Electron-microscopically, the tumor cells had electron dense round membrane-bounded granules resembling non-B granules of pancreatic islet cells. With the immunoperoxidase procedure (PAP method), tumor cells nearly almost reacted to anti-vasoactive intestinal polypeptide (VIP) serum, which suggested that the tumor of the present case had the capability to produce VIP. PMID- 6251697 TI - The occurrence of the trehalose fermenting, tetracycline and polymyxin resistant phenotype among the Enterobacteriaceae. AB - In Proteus morganii, P. mirabilis, and Providencia stuartii the ability to ferment trehalose and resistance to tetracycline were associated in 90%-97% of the strains. The same was true of at least 78% of the strains of Serratia marcescens. Proteus vulgaris showed a more quantitative association of the two traits. As the characters occur independently in 3-10% of the strains, the association is considered to be due to simultaneous selection in some natural niche. The trehalose fermenting, tetracycline and polymyxin resistant species ferment few other carbohydrates, fewer than the remainder of the Serratia species. PMID- 6251698 TI - Sodium nitroprusside induced cGMP accumulation in isolated frog skin epithelium. Effect on cAMP, hydroosmotic and natriferic response to antidiuretic horomone. AB - The cGMP content of isolated frog skin epithelia has been measured, and the basal level was found to be 14.3 +/- 1.7 fmol/mg dry lweight. 0.1 mM sodium nitroprusside induced a 10-fold increase in the cGNP level within 5 min after which it rose more slowly. The maximum increase in cGMP level was obtained with 1 mM sodium nitroprusside, giving a 20-50-fold increase. 1 mM sodium nitroprusside per se had no effect on osmotic water flow or active sodium transport. On the other hand, the osmotic water flow response to arginine vasotocin was somewhat enhanced in skins which had been pretreated with 1 mM sodium nitroprusside; thus the water flow responses to 1 and 31 ng/ml arginine vasotocin were on the average 31 and 14% higher in skins exposed to sodium nitroprusside than in control skins. Sodium nitroprusside had no effect on the increment in sodium transport rate elicited by arginine vasotocin. Sodium nitroprusside alone increased the cAMP level slightly; the enhanced cAMP level, reached after 30 min incubation with 40 ng/ml arginine vasotocin, was 20% higher in the presence of 1 mM sodium nitroprusside. IN CONCLUSION: cGMP has no effect on osmotic water flow nor on active sodium transport and is not involved in the regulation of sodium transport by antidiuretic hormone. However, cGMP (or sodium nitroprusside) has a moderate effect on the hormone-stimulated osmotic water flow. PMID- 6251699 TI - Determination of antibody to hepatitis B core antigen by radioimmunoassay in chronic liver disease. AB - Antibody to hepatitis B core antigen (anti-HBc) was measured by radioimmunoassay using CORAB (Abbott Laboratories) in 10 cases of chronic persistent hepatitis (CPH), 46 cases of chronic aggressive hepatitis (CAH), 33 cases of liver cirrhosis (LC) and 53 cases of hepatocellular carcinoma (HCC) in relation to hepatitis B surface antigen (HBsAg) and its antibody (anti-HBs). Ninety-eight point four percent of patients with HBsAg and 93.8% of patients with anti-HBs were positive for anti-HBc and the titers of anti-HBc in patients with HBsAg were significantly higher than those with anti-HBs. Thirty-five point five percent of patients negative for either HBsAg or anti-HBs were positive for anti-HBc. The titers of anti-HBc in patients with CPH, CAH and LC were relatively low, whereas 7 (46.8%) of the HCC patients negative for either HBsAg or anti-HBc had high titers of anti-HBc. The significance of the presence of anti-HBc alone is discussed. PMID- 6251700 TI - [Prolactin and galactorrhea]. PMID- 6251701 TI - Lysosomal acridine orange uptake in fibroblasts transformed by SV40 or human cytomegalovirus. AB - Lysosomes of living human fibroblasts, SV40-transformed rat fibroblasts and human CMV-transformed hamster fibroblasts were examined by fluorescence microscopy after pretreatment with acridine orange at a supravital concentrations (5 x 10(6) M). Dye uptake by human primary fibroblast lysosomes was considerable and independent of the age of the cultures. In the transformed cultures, cytoplasmic granular red fluorescence indicating lysosomal acridine orange uptake could not be observed in part of the cells; cells showing no cytoplasmic granular fluorescence appeared as early as after 48 hr incubation and were growing in dependence on the age of the culture. Staining of living cells by acridine orange solutions at supravital concentration is a practicable method for the examination of functional changes of lysosomes. PMID- 6251702 TI - Specific antibodies to viruses HL-23 and BILN in the blood plasma of patients with acute myelogenous leukaemia and with potential preleukaemia. AB - Blood plasma samples from patients with acute myelogenous leukaemia (AML) or potential preleukaemia and from control subjects were tested for antibodies to the viruses HL-23 and BILN by membrane immunofluorescence. Of 15 patients with untreated AML, three, each having a low peripheral leucocyte count at the time of sampling, had detectable antibodies. Antibodies were present in the plasma of 5 out of 8 AML patients being in remission as a result of chemotherapy. In these cases, the antibody levels significantly exceeded those demonstrated in the untreated cases. Of 12 patients with potential preleukaemia, five proved to be positive. Of the 7 antibody-negative patients, four developed manifest leukaemia within 12-18 months after the first testing. The results are suggestive of a favourable prognostic role of the presence of the antibodies under study. In the majority of the antibody-positive AML and potential preleukameia cases antibodies were detectable to both components of the HL-23 virus. Of 30 control subjects, three had demonstrable antibodies to the BILN virus. PMID- 6251703 TI - Genetic analysis of hormone-sensitive adenylate cyclase. PMID- 6251704 TI - Cyclic nucleotides in bone and mineral metabolism. II. Cyclic nucleotides and the renal regulation of mineral metabolism. PMID- 6251705 TI - Cyclic nucleotides in hormonal regulation of adrenocortical function. PMID- 6251706 TI - Phosphorylation of contractile proteins in relation to muscle function. PMID- 6251707 TI - The phosphoprotein phosphatases: properties of the enzymes involved in the regulation of glycogen metabolism. PMID- 6251708 TI - Antibody-mediated destruction of virus-infected cells. PMID- 6251709 TI - Aleutian disease of mink. PMID- 6251710 TI - Relationship of rubella, herpes simplex, cytomegalovirus, and certain other viral disabilities. PMID- 6251711 TI - Influence of refined cellulose on human bowel function and calcium and magnesium balance. AB - The effect of cellulose purified from wood pulp on wet and dry stool weights, gastrointestinal transit time (TT), frequency of defecation, and calcium and magnesium balances was tested. Seven healthy women consumed a low fiber diet of constant composition (percentage of total kcal: 23% protein, 30% fat, 47% carbohydrate) and the same metabolically controlled diet to which 16 g of refined cellulose (Solka Floc) was added. Each diet was consumed for approximately one month. The neutral detergent fiber contents of the two diets were 9.5 and 23.5 g, respectively. Cellulose consumption significantly increased mean daily wet stool weight from 74.6 +/- 23.4 (SD) to 130.5 +/- 29.4 g, mean daily dry fecal weight from 19.1 +/- 4.2 to 39.5 +/- 7.7 g, and frequency of defecatin from 0.85 +/- 0.2 to 1.10 +/- 0.29/day. Cellulose effectively shortened TT of two subjects with initially slow TT (7 days), but mean TT of all subjects was not significantly affected when fiber was added to the diet. Fecal excretions of calcium and magnesium were significantly greater when the diet containing cellulose was fed, and only calcium balance was significantly more negative. These results suggest that moderate levels of refined cellulose adversely increased fecal losses of calcium and magnesium. All other indices of bowel function remained within normal ranges. PMID- 6251712 TI - Ground-glass cells in hepatocellular carcinoma. AB - Hematoxylin and eosin-stained sections representing ten cases of hepatocellular carcinoma showed many tumor cells with ground-glass cytoplasm identical to that found in hepatocytes containing hepatitis B surface antigen (HBsAg). However, the aldehyde fuchsin stain was negative, as were the were the immunoperoxisidase stains for HBsAg and core antigen (HBcAg). Electron microscopically, the ground glass appearance corresponded to the presence of non-membrane-bound amorphous or fibrillar inclusions. Immunohistochemically, the ground-glass material reacted with antiserum to human fibrinogen, suggesting synthesis of this protein by the carcinoma cells. Although the ground-glass appearance in hepatocellular carcinomas may sometimes be associated with HBsAg, special stains or technics are necessary to confirm its presence. PMID- 6251714 TI - Relation of culture site to the recovery of nonpolio enteroviruses. AB - The relative utilities of rectal swab, throat swab, stool, and cerebrospinal fluid cultures for the recovery of nonpolio enteroviruses were retrospectively evaluated for 81 patients who had one or more positive cultures. Of 33 stool cultures submitted, 32 (97%) were positive; of 52 throat swabs submitted, 35 (67%) were positive; of 29 rectal swabs, 20 (69%) were positive. Of 16 patients for whom both sites were simultaneously sampled, stool cultures were positive for 15, but throat cultures were positive for only six. Seven other patients who had positive throat cultures had simultaneous rectal swab cultures that were negative. For patients who had aseptic meningitis, cerebrospinal fluid was positive in only nine of 21 cultures, whereas stool was positive in all of 12 cultures. Stool should be cultured for all patients suspected of having nonpolio enterovirus infections; rectal swabs are inadequate substitutes for stool cultures. PMID- 6251713 TI - Antibiotic susceptibility testing of Bordetella pertussis. AB - A tube dilution test to evaluate the effectiveness of antibiotics against Bordetella pertussis is described. Five B. pertussis strains, including a well characterized research strain and four fresh clinical isolates, were tested with several antibiotics. Erythromycin showed the highest in-vitro activity of the antibiotics tested. A concentration of 0.12 microgram/ml was bacteriostatic for all strains, while 2 microgram/ml was bactericidal. Minimal inhibitory and minimal bactericidal concentrations for ampicillin by tube tests were found to be higher than values previously reported for agar plate tests. PMID- 6251715 TI - Activation of human polyomavirus infection-detection by cytologic technics. AB - Human polyomaviruses produce characteristic large basophilic nuclear inclusions in urothelial cells. Cytologic screening of urinary sediment for inclusion bearing cells permits the identification of persons who are actively excreting these viruses. The human polyomavirus-induced changes may be differentiated from changes induced by other viruses and from cancer by transmission electron microscopy of infected cells. Cytologic evidence of virus infection was detected in five of 37 cancer patients receiving various treatments, two of whom were also diabetic, and in two of 84 adult patients who had diabetes mellitus. The monitoring of 3,648 urine samples sent for routine cytologic examination revealed 12 additional patients to have cytologic changes of human polyomavirus infection. Electron microscopy confirmed the presence of polyomavirus particles in seven of the 19 cytologically positive specimens. Previous reports of human polyomavirus excretion have been confined to describing patients whose immunity may have been impaired by drug therapy, congenital disease, or pregnancy. This study indicates that cytologic evidence of active human polyomavirus infection may be found among patients receiving various treatments for a number of medical disorders not usually associated with immunologic defects. Further studies to identify factors concerned in the reactivation of human polyomavirus are indicated. PMID- 6251716 TI - Childhood brachial plexus neuropathy. PMID- 6251717 TI - Demonstration of cavitated hepatic masses by "skinny needle" transhepatic cholangiography. The need for ultrasonic or computed tomography evaluation in obstructive jaundice. AB - A patient with cholestatic jaundice, ascending cholangitis and recent development of sepsis had an unsuspected intrahepatic abscess discovered by "skinny needle" percutaneous transhepatic cholangiography (PTC). Ultrasound and computed tomography (CT) evaluation were omitted in the work-up because of the clinical impression that the disease was almost certainly due to an obstructing calculus. The unsuspected cause of cholestasis was found by PTC but would have more easily been detected by other means, as a second similar case illustrates. PMID- 6251718 TI - Diet and cancer. PMID- 6251719 TI - Inhibition of platelet aggregation with histamine. AB - A sensitive in vitro technique was used to demonstrate the inhibitory effects of histamine or human blood platelets. Platelet aggregation by epinephrine was completely inhibited at 10(-3) M concentrations of histamine. Persistent elevations of cyclic AMP levels were shown to occur in the platelets when histamine was added and corresponded to the inhibitory effects on platelet aggregation. In contradistinction to the analogous inhibitory effects by histamine on other cellular elements of the hematopoietic system, this inhibitory effect on platelets could not be blocked by equimolar concentrations of either of the classes of histamine antagonists presently available. It is suggested that there may be other additional histamine receptors on the surface of membranes of platelets or that histamine mediated its inhibitory effect on platelets through a mechanism other than surface receptors. PMID- 6251720 TI - Relationship of SV40 T-antigen expression in vitro to disorders of bone marrow function. AB - Skin fibroblasts from patients with a variety of hematologic disorders were infected with SV40 virus in vitro in attempts to discover the reason for increased susceptibility of Fanconi anemia cells to this transforming virus. The proportion of skin fibroblasts expressing SV40 T-antigen by immunofluorescent methods was elevated in 12 patients with Fanconi anemia and in seven of nine obligate heterozygous relatives. Elevated expression was also observed in three patients with other hematological disorders at high risk of acute non-lymphocytic leukemia, but was not apparent in seven sporadic aplastic anemia patients or four of their relatives. T-antigen expression was elevated in about one-half of patients with thrombocytopenia-absent radius syndrome and related conditions, with familial aplastic anemia, and in their normal relatives. In the conditions under study, elevated T-antigen expression seemed clearly correlated with predisposition to leukemia, which may be genetically determined, but it was not associated with cytogenetic or anemic manifestations. PMID- 6251722 TI - Immunofluorescent detection of angiotensin-converting enzyme (ACE) in Gaucher cells. AB - The cellular localization of the elevated angiotensin-converting enzyme (ACE) in the spleen of a patient with Gaucher's disease was examined by immunofluorescence using an antibody prepared against highly purified human lung enzyme. Intense ACE specific cytoplasmic fluorescence was observed in Gaucher cells, but not in various controls, indicating the localization of large quantities of enzyme in these cells. These results and the demonstrated capability of mononuclear phagocytes for marked induction of this enzyme suggest the possibility that induction of active synthesis of ACE in Gaucher cells may be responsible for the elevated enzyme levels in the serum and spleen of patients with Gaucher's disease. PMID- 6251721 TI - 1,25(OH)2D3 is not the only D metabolite involved in the pathogenesis of osteomalacia. AB - Three patients are described in whom there was no simple correlation between plasma 1,25(OH)2D3 concentration and the occurrence of osteomalacia. One patient had severe osteomalacia with high plasma 1,25(OH)2D3 and normal mineral ion product; the second had a normal mineral ion product and no evidence of osteomalacia even though plasma 1,25(OH)2D3 was undetectable; and the third had osteomalacia, low plasma 1,25(OH)2D3 and a reduced mineral ion product. In considering these data in the light of presently available information, it is concluded that osteomalacia can occur as a consequence of a lack of a vitamin D metabolite other than 1,25(OH)2D3, or a consequence of a reduced mineral ion product, but not as a consequence of 1,25(OH)2D3 lack if the mineral ion product is normally maintained and other D metabolites are present. However, a deficiency of 1,25(OH)2D3 normally leads to a reduction in the mineral ion product hence 1,25(OH)2D3 deficiency may play a role in the development of certain forms of osteomalacia. PMID- 6251723 TI - Late recurrences of gestational trophoblastic neoplasia. AB - Presented are two cases of recurrence of gestational trophoblastic neoplasia more than 1 year after apparently successful therapy. Both patients initially had had nonmetastatic disease, were clinically free of disease, and had had repetitively negative serum radioimmunoassay titers for the beta subunit of human chorionic gonadotropin for 2 to 3 years. The development of these late recurrences re emphasizes the need for prolonged follow-up monitoring of patients after apparently successful therapy for gestational trophoblastic neoplasia. PMID- 6251724 TI - Thyroid function in gestational trophoblastic neoplasia: evidence that the thyrotropic activity of chorionic gonadotropin mediates the thyrotoxicosis of choriocarcinoma. AB - An investigation was made of thyroid function in 20 patients with gestational trophoblastic neoplasia. Two patients were judged to be overtly thyrotoxic on the basis of the symptoms and physical findings; both patients had widely metastatic choriocarcinoma, markedly increased serum T4 levels (21.4 and 27.7 micrograms/100 ml), and extremely high levels of serum human chorionic gonadotropin (hCG) (3,220 and 6,720 IU/ml) relative to those of normal gestation(< 100 IU/ml). Three other patients had moderately increased serum T4 levels (13 to 17.1 micrograms/100 ml), moderately increased serum hCG levels (110 to 310 IU/ml), and findings on clinical examination which suggested euthyroidism. Using the mouse thyroid bioassay, we found that the biologic characteristics of the thyroid-stimulating factor were those of purified hCG, and that the levels of thyroid-stimulating activity in both serum and urine correlated closely with the levels of hCG. These results provide evidence that the thyroid-stimulating activity intrinsic to the hCG molecule plays the central pathophysiologic role in choriocarcinoma associated thyrotoxicosis. PMID- 6251726 TI - Benign glandular inclusions in para-aortic lymph nodes: A cause for false positive lymphangiography. PMID- 6251725 TI - Trophoblastic disease monitoring: Evaluation of pregnancy-specific beta 1 glycoprotein. AB - Pregnancy-specific beta 1-glycoprotein (SP1) was evaluated as a potential marker protein for monitoring trophoblastic disease. Four patients with post-molar pregnancy accompanied by spontaneous titer remission and three patients with nonmetastatic trophoblastic disease were found to have regression curves for both human chorionic gonadotropin (hCG) and SP, which closely followed each other. Of three patients with metastatic choriocarcinoma, two were shown to have discordant hCG and SP1 patterns, SP1 in both cases was plateauing or rising while hCG continued to fall. Two other patients are described, one with a spontaneous remission, and one who previously had had choriocarcinoma and was found to have low levels of hCG with higher levels of SP1. PMID- 6251727 TI - Effect of phenol on conduction and synaptic transmission block. AB - The effect of phenol on nerve conduction and ganglionic synaptic transmission has been studied on sciatic nerve and on the VIIIth sympathetic ganglion of the frog. Ganglionic synaptic transmission block occurred at lower concentration than axonal conduction block. Both, conduction and synaptic transmission recovered in Ringer's solutions after 10 minutes. CaCl2 5.4 mM antagonized partially the axonal conduction block and EGTA in Ringer's solution without CaCl2 increased the effect of phenol on axonal conduction block on desheated sciatic nerve. Early in the experiments phenol had a weaker effect than procaine but at 10 minutes the effect of procaine became steady state and the effect of phenol continued to increase. PMID- 6251728 TI - The use of a correctional setting for follow-up care of psychiatrically disturbed adolescents. AB - The authors studied the first 88 adolescents boys who were placed on the secure unit of a correctional school during an 18-month period and found that 52 (59.1%) of the boys had previously received psychiatric residential treatment or psychiatric hospitalization. The authors hypothesize that many of these boys may have been transferred from a psychiatric setting to a correctional facility during adolescence when long-standing aberrant behaviors became more threatening to staff. At present the number of psychiatric hospital beds is decreasing and the criteria for hospitalization of children are becoming more stringent. The data indicate that correctional facilities are now expected to function as psychiatric treatment centers for disturbed adolescents no longer welcome in therapeutic settings. PMID- 6251729 TI - [Plasma determination of AMPc and GMPc in normal subjects in Mexico City]. PMID- 6251730 TI - High-resolution preparative gel electrophoresis: separation and recovery of functional messenger RNA species. PMID- 6251731 TI - An improved assay and some properties of phosphoglycolate phosphatase. PMID- 6251732 TI - The use of rotating disk voltammetry for the determination of homogeneous small molecule--redox protein reaction rates. PMID- 6251733 TI - A filter assay specific to Eco helix-destablizing Protein I in crude extracts. PMID- 6251734 TI - Effects of serum components on the morphology of Sertoli cells in culture. AB - Studies of Sertoli cell structure, maturation, and function have been aided by the use of in vitro systems. Although numerous papers have appeared that utilize the Sertoli cell culture model, few papers have dealt with the characterization of these cells under various culture environments. Recently, it has been reported that the addition of serum to the culture medium prevents induction of long cytoplasmic appendages in cultured Sertoli cells that have been treated with FSH, TSH, or c-AMP. The purpose of this investigation was to determine which serum components, obtained by gel filtration, are capable of inhibiting the morphological response induced by FSH, TSH, or c-AMP. Sertoli cell-enriched cultures were prepared using collagenase and trypsin digestion, each followed by gravity sedimentation. Untreated cells grown on plastic or glass substrates assumed an epithelioid appearance after several days. Cells treated with FSH, TSH, or c-AMP formed long cytoplasmic appendages after 1-2 days. This response was prevented or reversed by the addition of fetal calf serum (10%), crystallized bovine serum albumin (0.25%-2%), or purified albumin obtained by gel filtration of whole serum (0.25%). It was also found that fractions that elute between the void volume and the initial albumin fractions (molecular weights of approximately 50,000 and greater) mimic the hormone-induced response after only 10-12 hours. The results of this investigation indicate that albumin is the primary serum component responsible for inhibiting morphological alterations induced by FSH, TSH, and c-AMP. Furthermore, it is apparent that the production of long filamentous cytoplasmic appendages in Sertoli cells can be induced by a wide variety of substances. PMID- 6251736 TI - [Clinical study of tercuronium]. PMID- 6251735 TI - Isolation, culture and characterization of epithelial cells derived from rat ventral prostate. AB - Epithelial-cell enriched primary cultures have been established from rat ventral prostate (RVP). Minced ventral prostates were dissociated with 0.5% collagenase in F12K tissue culture medium containing 1% fetal bovine serum. This treatment resulted in the gradual removal of stromal elements from the base of the epithelial cells. After 60 minutes of digestion the aggregates of epithelial cells were washed and plated at high density in F12K plus 10% horse serum. After 48 hours in vitro the unattached cells were removed from the culture dishes, washed, and reinoculated into new culture vessels containing fresh medium. After 96 hours in vitro, the aggregates had attached to the culture vessels and spread out to yield discrete patches of epithelial cells. By 144 hours in vitro the patches of cells had grown and coalesced to form a semi-confluent monolayer of epithelial cells. Ultrastructrual examination of these cultures indicated that adjacent cells were joined by desmosomes and tight junctions and had formed "lumen-like structures" into which projected microvilli. In addition, the cells contained secretory granules and tonofilaments, giving them a morphological appearance similar to prostate epithelial cells in the intact organ. The primary cultures also retained histochemical activities for acid phosphatase, beta glucuronidase, and succinic dehydrogenase that were similar to the intact organ. PMID- 6251737 TI - [Changes in protein metabolism and humoral immunity and their correction in the postoperative period in children with nephroblastoma]. PMID- 6251738 TI - A screening test for influenza immunity: preimmunization antibody titers to influenza virus antigens in atopic patients. AB - Antibody titers to three common strains of influenza virus, including the Swine Flu strain, were determined in 152 patients in an allergy and pediatric allergy practice prior to planned immunization with influenza vaccine. Because allergic patients are considered to be more prone to hypersensitivity reactions than individuals who are non-allergic, it was deemed prudent to screen for patients who might have pre-existing protective levels of antibody to the viruses. A considerable number of the 152 patients were found to have titers of 1:20 or 1:40 to one or more of the three influenza strains, including the Swine Flu strain. The largest percentage of positive antibody levels was found to be to the A Victoria strain which has recently been most prevalent in the northeastern United States. The lowest numbers of patients with protective antibody levels were for the Swine Flu strain. Nevertheless, the highest titers occurred with patient specimens tested against the Swine Flu strain. Approximately one-quarter of the patients showed significant levels of antibody (1:40 or more) to one or more of the virus antigens and thus were not vaccinated, avoiding the possibility of untoward areactions which habe been observed in some individuals who have been given the vaccine. PMID- 6251739 TI - The role of cyclic amp in the process of specific hyposensitization. AB - The parenteral administration of a specific allergen produces a local edema due to the liberation of histamine. We have investigated the plasmatic cyclic AMPO in this reaction. A group of allergic patients (36 in all) with asthma or rhinitis or both diseases and with a very positive prick skin test was studied. The level of cyclic AMP was investigated before and after injecting the patients with the specific hyposensitizing extract. The average levels of cyclic AMP in our patients before the injection of the specific extract were 2.6 pmol/ml and this corresponded to the normal levels found in the controls in our laboratory (13.8 pmol/ml). After the injection of the allergen these levels increased by an amount that varied between 0.1 pmol/ml and 33.4 pmol/ml in 61.1% of the cases (p > 0.05). The cyclic AMP decreased by an amount that varied between 0.1 pmol/ml and 16.0 pmol/ml in 38.8% of the patients (p > 0.05). PMID- 6251740 TI - Lack of detection of factor VIII in sarcoidal epithelioid cells. AB - We investigated the possibility that epithelioid cells in sarcoidosis contain abundant angiotensin-converting enzyme, because these cells are derived from endothelial cells, which normally contain the enzyme in abundance. Granulomas from 9 patients with sarcoidosis were examined for the presence of the endothelial cell marker, factor VIII, by immunofluorescence microscopy using monospecific anti-human factor VIII antibody. Strong factor VIII-specific fluorescence was detected in the endothelial cells but no fluorescence was observed in the epithelioid cells. These results do not support the origin of epithelioid cells in sarcoidosis from endothelial cells as an explanation for their abundance of angiotensin-converting enzyme. PMID- 6251742 TI - [Herpes simplex encephalitis (author's transl)]. AB - A 25 months old male with herpes simplex virus encephalitis is presented. After analizing the diagnostic value of several parameters, the E. E. G. findings during the first days of the illness are specially emphasized. Results obtained until now with every type of therapy are reviewed. PMID- 6251741 TI - Characterization of adenylate cyclase activity in asthmatic neutrophil sonicates. PMID- 6251743 TI - [Structure and characterization of the principal constituents of dietary fiber]. PMID- 6251744 TI - Ionic currents in molluscan soma. PMID- 6251745 TI - Dementia of the Alzheimer type. PMID- 6251746 TI - [Use of the artificial pancreas in the diagnosis and management of an insulinoma (author's transl)]. AB - The artificial endocrine pancreas is generally used to control blood glucose in brittle diabetic patients. In this study, it was applied to the diagnosis and surgical management of a pancreatic insulinoma. Several tests were performed without the risks inherent to severe hypoglycemia. It was also used during surgery, permitting an optimal blood glucose control. PMID- 6251747 TI - Comparative effects of an inflammatory reaction on the resistance of mice to bacterial and viral infections. AB - The induction in mice of a sterile subcutaneous granuloma exerted no influence upon the mortality following their infection with herpes type 1, murine hepatitis or encephalomyocarditis viruses. Attempts to reproduce the resistance -- which has been found to occur as a result of the granulomatous reaction, in the case of bacterial, fungal or protozoa infections and tumour invasions -- by varying the route and timing of the virus inoculation or the strain of mice have failed. We conclude that it is not merely through their inflammatory properties that some non-specific immunostimulating substances enhance resistance against viral infection. PMID- 6251748 TI - Control of nucleotide pools in mammalian cells. AB - The deoxyribonucleoside triphosphates (dNTPs) are produced via reduction of the corresponding nucleoside diphosphates and subsequent phosphorylation. The reduction step is catalyzed by the enzyme ribonucleoside diphosphate reductase, an enzyme which is induced in S phase cells. The activity and specificity of this enzyme is controlled by dNTPs and ATP, and this feedback mechanism provides a stringent control of the concentrations of the dNTPs themselves. The pools of the dNTPs vary during the cell cycle and are largest is S phase cells. Moreover, in S phase cells, the difference between the largest pool (dCTP) and the smallest pool (dGTP), is about 20-fold. Also, the pools are compartmentalized into cytoplasmic and nuclear pools, and this compartmentalization is most pronounced in S phase cells. In such cells, the total nuclear concentration of dNTPs is about micronM. Mainly by use of virus-infected cells, results were obtained which indicate a direct involvement of a deoxycytidine nucleotide in the regulation of DNA synthesis. PMID- 6251749 TI - In vitro antimicrobial activity of cefotaxime, a new cephalosporin. AB - Cefotaxime, a new semisynthetic cephalosporin derivative, showed a broad spectrum of antibacterial activity against clinically isolated strains of gram-positive and gram-negative bacteria. This cephalosporin was slightly less active than cefazolin against Staphylococcus aureus but 4 to 300 times as active as carbenicillin against gram-negative organisms, including Pseudomonas aeruginosa, Pseudomonas cepacia, Enterobacter cloacae, and Serratia marcescens. Cefotaxime was the most active compound against members of the Enterobacteriaceae and 20- to 100-fold more active than cefoxitin against the indole-positive Proteus group. The minimal bactericidal concentrations of the compound were identical to, or two times higher than, the minimal inhibitory concentrations against Escherichia coli and P. aeruginosa and four times higher against S. marcescens. A reduction of inoculum size decreased greatly the minimal inhibitory and bactericidal concentrations of cefotaxime against E. coli P. aeruginosa, and S. marcescens. The antibiotic was very stable to penicillinase and cephalosporinase produced by gram-negative bacteria, including Proteus vulgaris. PMID- 6251750 TI - Cefotaxime: in vitro activity and tentative interpretive standards for disk susceptibility testing. AB - Tested against 9,412 recent clinical isolates, cefotaxime exhibited 8 to 64 times greater activity against the Enterobacteriaceae than did cephalothin and two to four times greater activity against Pseudomonas aeruginosa, but only one-half to one-eighth the activity of cephalothin against staphylococci. Using 420 different clinical isolates, but with comparable minimal inhibitory concentration (MIC) distributions, disk diffusion-MIC regression analyses were performed, using 5- and 30-micrograms cefotaxime disks. Cefotaxime MIC susceptible and resistant breakpoints of less than or equal to 8 and greater than 32 micrograms/ml are tentatively proposed. Based on the MIC breakpoints, the data showed the best discrimination among the three susceptibility categories (susceptible, indeterminate, and resistant) when the 30-micrograms cefotaxime disk was used. The zone diameter breakpoints as determined by the error rate-bounded method and regression analysis were greater than or equal to 23 mm for susceptible, 15 to 22 mm for indeterminate, and less than or equal to 14 mm for resistant. PMID- 6251751 TI - Skin test with Varicella-zoster virus antigen on herpes zoster patients. AB - Intracutaneous injection of Varicella-zoster (V-Z) viral antigen was performed on 55 patients with herpes zoster. All of them reacted positively after 10 days. The patients in the acute stage responded weakly wereas those in the convalescent phase developed a stronger reaction. The intensity of the reaction did not correlate with the number of days of illness. Positive reactions were observed in those patients who had suffered from herpes zoster several years ago. Complement fixing antibody titers did not parallel the intensity of skin reaction. PMID- 6251752 TI - Regulation of ovarian LH/HCG receptors in pregnant rats. PMID- 6251753 TI - Regulation of ovarian LH/HCG receptors in immature rats after injection of HCG. AB - In 24-day-old rats the reappearance of ovarian HCG-receptors up to day 4 after the injection of 200 IU HCG was due only to receptors in non-luteal cells. The receptor capacity increase observed on days 6 and 7 after the hormone injecion resulted from newly synthesized binding sites in luteinizing ovaries. Bromocriptine or an antiestrogen inhibited this receptor synthesis. PMID- 6251755 TI - Serum immunoreactive prolyl hydroxylase in inflammatory rheumatic diseases. AB - Serum immunoreactive prolyl hydroxylase protein (S-IRPH) was measured in 56 patients with inflammatory rheumatic diseases, and the values were compared with those in 32 control subjects. S-IRPH was above the 95% confidence limit of the controls in about 70% of the patients with active systemic lupus erythematosus, rheumatoid arthritis, scleroderma, Reiter's syndrome, Sjogren's syndrome, polyarteritis nodosa, or polymyositis. Raised values were observed in about half of the patients with an erythrocyte sedimentation rate (ESR) of 21-50 and in about 90% of those with ESR of over 50, whereas only about 10% of the patients with an inactive disease had an S-IRPH concentration exceeding this limit. Only 1 out of 8 patients with active ankylosing spondylitis had a raised S-IRPH value. The results support previous data indicating that significant changes in collagen metabolism occur in active connective tissue diseases. Assays of S-IRPH might be of some value in assessing the activity of these diseases and in monitoring the treatment provided. PMID- 6251754 TI - Determination and properties of proteohormone receptors in malignant gynecological tumors with special reference to lactogen receptors in human breast cancer. AB - Proteohormone receptors have been demonstrated in gynecological malignancies, but more sensitive methods for measurement of such receptors are required and should be a matter of intensive research. The clinical response of hormone-dependent tumors to endocrine therapy has not yet been correlated with the occurrence of proteo-hormone receptors in neoplastic tissue from gynecological patients and such studies are required. PMID- 6251756 TI - Formation of calcium pyrophosphate crystals in vitro: implications for calcium pyrophosphate crystal deposition disease (pseudogout). AB - Little is known about how calcium pyrophosphate dihydrate (CaPPD) crystals form in vivo and give rise to chondrocalcinosis or pseudogout (pyrophosphate arthropathy or calcium pyrophosphate crystal deposition disease). In this study a simple method has been devised to define the conditions necessary for the deposition of crystals in vitro. Crystal formation is monitored by (45)Ca in the presence of 1.5 mmol/l Ca and increasing concentrations of inorganic pyrophosphate (PPi) under simulated physiological conditions of pH and ionic strength. Concentrations of PPi required to initiate crystal formation were about 40 mmol/l in the absence and 175 mmol/l in the presence of 0.5 mmol/l Mg(2+) at pH 7.4. Less PPi was required at higher pH values. The naturally occurring monoclinic and triclinic forms of CaPPD were produced after prolonged incubation in vitro, but the initial deposits were amorphous or orthorhombic. The physiological significance of these observations is discussed. Since much higher concentrations of PPi are required to form crystals in vitro than are found to occur naturally in synovial fluids from patients with pyrophosphate arthropathy, it is suggested that crystals are more likely to deposit initially within cartilage and that nucleating mechanisms may be important in vivo. Since other workers have observed a slow interconversion of other calcium pyrophosphate crystal forms into monoclinic and triclinic allomorphs under laboratory conditions, the reason why only these 2 forms occur under clinical conditions may reflect the long time available in vivo for the formation of crystals. PMID- 6251757 TI - 5' nucleotidase activity in the human synovial lining in rheumatoid arthritis. AB - 5'-Nucleotidase (EC 3.1.3.5), a plasma membrane-bound enzyme, has been assayed in unfixed tissue sections of human synovium, activity being measured by scanning and integrating microdensitometry. Activity was markedly increased in the lining cells of the rheumatoid synovial membranes. PMID- 6251759 TI - Effect of cyproterone acetate on mouse adenohypophysis. I. The adrenocorticotrophs. AB - The adenohypophyses of adult male C57BL/6J mice pituitaries injected with cyproterone acetate for four weeks were examined with the electron microscope. The adrenocorticotrophs of the adenohypophysis showed an absence of the 200-nm granules that were lined along the plasma membrane, a decrease in profiles of rough endoplasmic reticulum, sparse distribution of ribosomes, and flatten Golgi membranes. It is believed the antiandrogen cyproterone acetate inhibited ACTH synthesis and release and that this was responsible for adrenocortical atrophy. PMID- 6251758 TI - Primary peptic ulcerations of the jejunum associated with islet cell tumors. Twenty-five-year appraisal. AB - A review of 42 patients with gastrinoma, who either survived five years or longer or who died during this period of evaluation, was carried out to define the surgical principles which might be combined with the recent trend toward cimetidine therapy. Thirty-four (80%) of the patients had total gastrectomy with an operative mortality rate of 2.3%, and eight patients (20%) had less than total gastrectomy. No tumor was found in six patients with hypergastrinemia and an abnormal secretin bolus whose five-year survival rate was 100%. Of the thirty-six patients having tissue proof of gastrinoma, twenty-two (61%) had complete resection of all gross tumor resulting in a 76% five-year survival rate. Fourteen patients had unresectable tumor or partial resection with a five-year survival rate of 21%. Complete gross tumor resection increased mean survival by six years (p < 0.01), but resulted in persistent eugastrinemia in only two patients. Long term survival was possible with a combination of vagotomy, lesser gastric procedures, tumor resection, and cimetidine, seven of eight patients living more than five years. Surgical management of gastrinoma should be directed toward aggressive tumor resection and vagotomy, with reliance on cimetidine therapy postoperatively to control the gastric hypersecretion. Total gastrectomy should be reserved for cimetidine failures and those who do not wish to take cimetidine for the rest of their lives. PMID- 6251760 TI - Effects of filipin, digitonin, and polymyxin b on plasma membrane of ram spermatozoa--an EM study. AB - The effects of three membrane-active agents, filipin, digitonin, and polymyxin B on the plasma membrane of ram spermatozoa have been studied by freeze-etch electron microscopy. Filipin and digitonin both reacted with cholesterol and caused visible membrane modification in cholesterol-rich regions, with filipin being a more specific agent than digitonin. Polymyxin B, which is known to interact specifically with negatively charged phospholipids of bacterial membranes, exhibited a selective binding and subsequent modification of sperm plasma membranes. This binding was shown to be inhibited in the presence of 1 mmol/1 Ca2+. We hence propose that both filipin and polymyxin B are useful cytological markers for specific biological molecules in eukaryote membranes- filipin for cholesterol, and polymyxin B for negatively charged phospholipids. PMID- 6251761 TI - First dose effect of the oral angiotensin converting enzyme inhibitor captopril. AB - Captopril was given orally to 24 patients with moderate to severe essential or renovascular hypertension, with variable degrees of sodium-volume depletion. Initiation of treatment resulted in orthostatic hypotension in 5 and in symptoms and signs of hypotension while still recumbent in 4; bradycardia accompanied the adverse hypotension which was relieved by iv atropine. After iv infusion of 1-2 liters of 0.9% NaCl patients cound resume their normal activities and be treated with captopril. The development of hypotension was related to the prevailing plasma renin level, which was partly determined by the degree of sodium-depletion and the aetiology of hypertension. The degree of sodium-depletion, the aetiology and severity of hypertension and heart rate did not contribute independently from plasma renin activity to the development of hypotension. PMID- 6251762 TI - Captopril: an oral angiotension converting enzyme inhibitor active in man. PMID- 6251764 TI - Inhibition of hypersensitivity reactions by 16(S)-methyl-20-methoxy-PGE2 (YPG 209) in animals. AB - The effects of 16(S)-methyl-20-methoxy-PGE2 (YPG-209) on hypersensitivity reactions were investigated in the rat, guinea-pig and mouse. Intravenously administered YPG-209 was 150 times as potent as disodium cromoglycate (DSCG) in the inhibitory effect on the IgE(mouse)-mediated 24 hr rat PCA. When administered intravenously to guinea-pigs, YPG-209 inhibited significantly the IgE (guinea pig)-mediated 8 day guinea-pig PCA, whereas DSCG exhibited no significant inhibitory effects. The oral doses of YPG-209 diminished both histamine and 5 hydroxytryptamine hypersensitivity of the Bordetella pertussis-treated mice. These results suggest that YPG-209 exhibits not only the prevention of mediator release but also the antimediator effect in laboratory animals. PMID- 6251763 TI - Prostaglandins: role in renin regulation and mediation of antihypertensive drug effects. AB - A role of prostaglandins in renin regulation has been recognized in animals and man. Indomethacin, a blocker of prostaglandin synthesis, lowers plasma renin activity, renal prostaglandin synthesis and causes sodium retention in man. It is shown that the sodium retaining effect of indomethacin can be separated from its effect on plasma renin activity. A more precise definition of the mechanisms whereby prostaglandins influence renin release is given showing that the baroreceptor and the macula densa mechanisms of renin release are affected by prostaglandins. Investigations aiming at the indentification of the prostaglandin responsible for cylooxygenase--dependent renin regulator reveal that PGI2 is a prominent prostaglandin biosynthesized in the renal cortex and causes renin release in vivo and in vitro. A hypothesis is presented which postulates that prostaglandin dependent renin release is mediated by prostacyclin. Various antihypertensive drug effects can be antagonized by blockers of prostaglandin biosynthesis. Possible mechanisms of such drug interactions between propranolol, hydralazine and diuretics on the one hand and indomethacin and aspirin on the other hand are discussed. PMID- 6251765 TI - Prazosin protects vascular alpha-adrenoceptors against irreversible blockade by phenoxybenzamine. AB - The interaction of prazosin with the vascular alpha-adrenoceptor was studied in isolated vessel preparations by means of receptor protection experiments. Prazosin was compared to phentolamine. Prazosin, like phentolamine protected the receptor against irreversible blockade by phenoxybenzamine. It is concluded that prazosin acts by a direct occupancy block of the vascular alpha-receptor. PMID- 6251767 TI - [Live vaccine for oral immunization against avian encephalomyelitis of fowl]. AB - Strain C 2653 have proved to be applicable with good success as a live vaccine to treat avian encephalomyelitis. The virus is excreted by immunised animals up to roughly three weeks from immunisation and absorbed by non-immunised animals. Propagation and excretion of the immunisation virus will bring about sufficient immunity of the entire herd, within something between four and eight weeks from immunisation. Something between two and four per cent of the individuals in one herd are treated by crop instillation, which works well in cases of floor keeping. Yet, contact of all animals with the immunisation virus cannot be ensured, if the same technique is applied to animals kept in cages. Administration of the vaccine in pressure compensating vessels of the cage nipple lines or valve-operated drinking grooves in floor-keeping fowl houses will increase the amount by vaccine needed by the factor of 2.5, as compared to crop instillation, but the entire stock will be immunised in a shorter period of time, with 80 per cent of man-hours being saved. Application to floor-kept animals can be further simplified, which was demonstrated by the experimental prototype of a new drug proportioning device. Five times more vaccine will be needed, as compared to crop instillation, but that higher quantity is offset by more savings in man-hours. PMID- 6251766 TI - A comparison of the cardiovascular effects of haloperidol, thioridazine and chlorpromazine HCl. AB - Transient hypotension, electrocardiographic conduction changes and cardiac arrhythmias have been reported with the use of certain anti-psychotic agents. To assess these observations, we compared the effects of haloperidol, thioridazine and chlorpromazine HCl on alpha-adrenergic receptors, mean aortic pressure, myocardial contractile force and myocardial electrophysiology in anesthetized dogs. The results from these studies indicated that, on a milligram basis, chlorpromazine HCl was equipotent to haloperidol, and thioridazine was 0.5 times as potent as haloperidol as an alpha-adrenergic receptor blocker and as a myocardial depressant. Each compound induced conduction nonhomogeneity in myocardial conducting tissue. However, as a neuroleptic, when tested in dogs, haloperidol was 50 times more potent than chlorpromazine HCl and 180 times more potent than thioridazine. The therapeutic safety indices (cardiovascular effect dose/neuroleptic dose) for haloperidol regarding alpha-adrenergic blockade, hypotension, myocardial depression and ventricular conduction delay were 4, 145, 235 and 125, respectively, whereas these indices for chlorpromazine and for thioridazine were 0.06, 2, 4, 6 and 0.05, 1, 3 and 1, respectively. Therefore, because of differences in neuroleptic potency, therapeutic doses of haloperidol are less likely to cause adverse cardiovascular effects than are those of either chlorpromazine HCl or thioridazine. PMID- 6251768 TI - [Use and effectiveness of live vaccines in industrialized livestock production]. AB - There is an inseparable correlation between higher livestock performance and animal health with many visible repercussions in terms of further intensification of livestock farming. This is the background against which immunobiological action is defined as a major element of all efforts which are undertaken for the purpose of ensuring high-stability and high-continuity and no-problem production. Underlined in this paper is the great role played by legal provisions for immunisation concepts as well as by straight-forward guidance, organisation, and documentation of all uses of live vaccines. Practical experience so far obtained from the use of vaccines and its effects under conditions of industrialised livestock farming is reported in this paper, with particular reference being made to swine fever and transmissible gastro-enteritis of swine. PMID- 6251769 TI - [Immunoprophylaxis against Marek's disease and its perspectives]. AB - An account is given of the present international position in immunoprophylactic control of Marek's disease. An assessment is made of the method used for immunisation in the GDR. In that context, reference is made to problems for which solutions will have to be found in the long run. PMID- 6251770 TI - [Certain properties of the Aujeszky live vaccine "Dessau" with special reference to laboratory diagnostic aspects]. AB - Aujeszky live vaccine "Dessau" proved to be apathogenetic to and unconditionally tolerable by pigs of all age groups, including pregnant sows. Transmission of Herpes virus suis vaccine strain from immunised individuals to non-immunised contact animals was not observed at all. Higher titres of virus-neutralising serum antibody with longer persistence were not attained until repeated vaccinations had been applied, using Aujeszky live vaccine "Dessau". Spherical detachment of single cells was the only manifestation in fowl embryo cell cultures to demonstrate the cytopathic action of the Herpes virus suis strain which had been used in the preparation of Aujeszky live vaccine "Dessau". This high-stability marker of Herpes virus suis vaccine strain "Tornau" can be readily and dependently differentiated from Herpes suis field strains with cytopathic effects in fowl embryo cell cultures which include not only spherical detachment of single cells but, as well, differentiated portions of giant cells. Those are the properties of Aujeszky live vaccine "Dessau" which provide favourable conditions for laboratory diagnosis to monitor the incidence of Aujeszky's disease in areas with different degrees of contamination. PMID- 6251771 TI - Prostaglandins, platelets, and schizophrenia. AB - Prostaglandin (PG) E1 enhances formation of 3H-adenosine-3',5'-cyclic monophasphate (3H-cAMP) in platelets pulse-labeled with 3H-adenine. This response was assessed as an index of receptor sensitivity and of PG function. Prostagladin E1-stimulated 3H-cAMP accumulation in paltelets from schizophrenics was significantly reduced compared with control subjects. Platelet incorporation of 3H-adenine and basal 3H-cAMP accumulation. We discuss the results in terms of the possible role of PGs in the etiopathology of schizophrenia and derivative implications for treatment. PMID- 6251773 TI - Bronchial carcinoid appearing as a breast mass. AB - Carcinoid tumors of the breast are extremely rare. We studied what is to our knowledge the second case of an extramammary carcinoid presenting initially as a breast mass. Varying degrees of ribbon, trabecular, acinar, and insular patterns were present in the primary bronchial tumor and in several secondary deposits, including the initial breast lesion. The cells were argyrophilic and contained round and membrane-bound electron-dense granules. Estrogen and progesterone receptors were present in a cerebral metastasis. Polypeptide hormones and 5 hydroxytryptamine were not detected by immunocytochemistry. PMID- 6251772 TI - Hormonal bioassay of gonadotropin-producing hepatoblastoma. AB - Hepatoblastoma was associated with signs of isosexual precocity in an 11-month old boy. Circulating gonadotropic hormone levels were elevated. Gonadotropic activity was demonstrated by bioassay in extracts of primary and metastatic tumor, and in media surrounding long-term tissue culture of the primary tumor. Morphology of the endocrine glands and bioassay of the pituitary gland obtained at autopsy indicated the presence of gonadotropins and other tropic hormones despite the physiologically abnormal hormone status. These ae the first direct studies of pituitary hormone content in this syndrome. PMID- 6251774 TI - Lymphocytes and urine in ceroid lipofuscinosis. AB - Pathognomonic ultrastructural inclusions were found in the lymphocytes of 16 patients with neuronal ceroid lipofuscinosis (Batten's disease) and in the urine of three of four of such patients. These inclusions remained type specific for each patient and were identical with deposits in nerve cells and other body tissues. They persisted in lymphocytes in short-term tissue culture, but disappeared with stimulation by phytohemagglutinin. Siblings had identical inclusions. None were present in heterozygotes. Examination of lymphocytes in the peripheral blood cells is an easy method to use in the diagnosis of ceroid lipofuscinosis, but it cannot be used to detect carriers. PMID- 6251775 TI - The late facilitation in H-reflex recovery cycles in different pyramidal lesions. AB - H-reflex amplitudes were recorded after stimulation of the tibial nerve and different electrical stimuli in 18 normal persons and 26 patients showing pyramidal spasticity (8 spastic spinal paralysis, 6 spastic hemiparesis, 12 spinal lesions). A just subthreshold stimulus of the tibial nerve facilitated the H-reflex in spastic patients slightly after about 300 ms (up to 113%), following an early strong facilitation (10 ms) and a longer lasting depression (20-200ms). Similar postinhibitory facilitation was obtained in spastic patients after ipsilateral stimulation of the plantar surface and after direct stimulation of the dorsal columns. Conditioning by contralateral stimuli of the posterior tibial nerve caused a slight late facilitation in both normal and spastic patients. This late facilitation did not correlate significantly with the severity of spasticity, but it was more pronounced in cerebral pyramidal lesions than in spinal ones. It is assumed that this postinhibitory facilitation is probably generated as a spinal rhythm, similar to the clonus, and that it is modulated from supraspinal structures. PMID- 6251776 TI - Progressive dementia with "diffuse Lewy-type inclusions' in cerebral cortex. A case report. AB - A 69-year-old male suffering from progressive dementia died 3 years after the beginning of his disease. The neuropathology of this case revealed the coexistence of senile changes, typical for Alzheimer's disease, and the characteristics of Parkinson's disease, namely, numerous senile plaques and neurofibrillary tangles in the cerebrum and neuronal loss with depigmentation in the substantia nigra and locus caeruleus. Lewy-type inclusions were distributed not only in the pigmented brain stem nuclei, but also diffusely in the CNS. The close nosological relationship between paralysis agitans and Alzheimer's disease is discussed. PMID- 6251777 TI - The production of COFAL test antiserum in pigeons. PMID- 6251778 TI - Clostridium perfringens food-borne disease and bacteriological analysis for strain identification. PMID- 6251779 TI - Breast cancer in Japan and United States: epidemiology, hormone receptors, pathology, and survival. AB - Breast cancer is the most common cancer among American women, whereas in Japan it ranks third behind gastric and uterine cancers. In spite of the relatively low incidence of breast cancer in Japan, a sharp increase in the frequency has been noted since 1966, which is decidedly related to change in dietary patterns in Japanese women. An increase of over 250% in dietary intake of fat has been noted during the past 15 years. Cancer is detected at an earlier stage in Japan as compared with the United States, and consequently the end result is significantly better. But the improved results could not be totally explained on the basis of early detection, since stage-for-stage the Japanese series appears to be consistently better than the US series by 10% in their ten-year survival rates. PMID- 6251780 TI - [Investigation of the feed value of straw]. AB - Two groups of four pigs each were fed ad libitum with rations containing 70.7% barley, 7.7% fish meal, 0.7% Sussopan, 0.9% mixed minerals and 20% straw meal. Group 1 received partly hydrolysed straw meal, group 2 untreated straw meal. When those rations were given, weight increase performances of 767 g per animal and day in group 1 and 537 g per animal and day in group 2 were achieved in a preliminary 30-day feeding period. On the basis ofthe weight of the feed remnants, a consumption of 19.7% dry matter of the straw meal (group 1) resp. 18,5% (group 2) of the total intake of dry matter could be ascertained. At an average live weight of 93 kg (group 1) resp. 87.5 kg (group 2) the digestibility of both rations was examined. A significant difference was only found for the crude protein fraction with an apparent digestibility of 74.6% in group 1 and of 79.1% in group 2. Those pigs which received partly hydrolysed straw meal consumed 71.4 g N per animal and day, of which 25,4% were excreted in feces and 32.4% in urine. Those animals which were fed with untreated straw meal consumed 62.9 g N per animals and day of which 20.8% were excreted in feces and 49.7% in urine. The higher N-excretion in feces could also be proved for most amino acids the feeding with partly hydrolysed straw meal. For arginine, serine, glutamic acid, proline, isoleucine and Leucine these differences were significant. Differences concerning N-retention could not be found between the groups. 25% of the organic matter of the partly hydrolysed straw meal, 9.4% of the crude fibre and 44.2% of the N-free extractives were digestible. Of the untreated straw, 12.9% of the organic matter, 5.5% ofthe crude fibres and 21.7% of the N-free extractives were digestible. 193 EFpig were calculated for partly hydrolysed and 105 EFpig for untreated straw meal per kg dry matter. The result of substracting the CaCl2 of the partly hydrolysed straw meal is 205 EFpig per kg dry matter of the straw. PMID- 6251781 TI - [The influence of various feedstuffs containing fat and protein on the digestibility of crude nutrients in young calves]. AB - Digestibility trials were carried out with calves, aged 3, 5, 7, 9, and 11 weeks, which were fed with feedstuffs of various energy and protein levels (various amounts of dried skim milk supplement with 146, 219, 323 g per day of the milk replacer Laktin) plus concentrate and hay. The purpose of the experiment was to find out what effect the amount of milk replacer varying daily had on the digestibility of the nutrients. The experiments confirm that the amount of milk replacer has a great influence on the digestibility of the crude fat. The amount of digestible crude fat consumed with the feed considerably influcenced the digestibility of the energy, it had little influence on the digestibility of the other nutrients, however. With increasing age the calves received more plant protein sources with a lower biologic value. Thus the digestibility of the protein in the complete ration was diminished as well. This shows that the digestibility was influenced by the protein quality, not, however, by the amount of crude protein. The digestibility of the dry matter andthe organic matter as well as of the N-free extractives in the feed ration diminished according to the changed composition with the increasing age of the animals; in constrast to this the digestibility of the crude fibres increased gradually. PMID- 6251782 TI - Glucosamine metabolism of herpes simplex virus infected cells. Inhibition of glycosylation by tunicamycin and 2-deoxy-D-glucose. AB - The formation of glucosamine-containing cell surface glycoproteins of herpes simplex virus (HSV) infected BMK cells was studied. Tunicamycin (TM) and 2-deoxy D-glucose (DG) were used as inhibitors. With both inhibitors the multiplication of HSV was inhibited. DG markedly reduced cellular uptake of radioactively labelled glucosamine while TM interfered with the processing of glucosamine into TCA-insoluble material. Gel filtration chromatography on Sephadex G50 gel of cell surface material released by trypsin and further prepared by digestion with pronase indicated that TM and DG reduced the apparent high molecular weights of virus induced surface glycoproteins. In presence of DG the accumulation of a class of glucosamine-containing heterosaccharides (MW less than 3000) not present on DG-free HSV infected cells was observed. In TM treated cells virtually all surface heterosaccharides with molecular weights exceeding 3000 and containing glucosamine disappeared. Moreover, a component compatible with a lipid-linked oligosaccharide present in DG treated cells was not observed in HSV infected TM treated cells. The results exemplifies some different steps in glucosamine metabolism of virus induced cell surface glycoproteins differently affected by tunicamycin and 2-deoxy-D-glucose. PMID- 6251783 TI - Infections of susceptible and resistant mouse strains with herpes simplex virus type 1 and 2. AB - The spread of HSV of type 1 and 2 was investigated after intraperitoneal, intraplantar and intracerebral infections of resistant (C57/bl) and susceptible (NMRI) mice. The virus spreads after i.p. infection to the spleen and the liver to the same extent in both strains of mice. However, virus is eliminated earlier in resistant mice. Intracerebral infections revealed a peculiar type of resistance of C57/bl mice especially for type 2 of HSV. HSV multiplies in the thymus at the early stage of infection and can be detected in this organ in sick mice of NMRI strain. HSV-1 and 2 can be detected in the spinal cord of C57/bl mice without sickness or death of these animals. PMID- 6251784 TI - Experimental skin infection with an acyclovir resistant herpes simplex virus mutant: response to antiviral treatment and protection against reinfection. AB - Skin infections induced in hairless mice with an Acyclovir resistant herpes simplex virus (HSV) mutant were not followed by the death of the animals, and the survivors had no evidence of latent infections in their sensory ganglia. However, mutant virus was detected in the ganglia during the acute phase of the infection. Mice inoculated with the mutant were fully protected against the fatal outcome of the infection when subsequently challenged with the relatively pathogenic parental virus. In addition the frequency of latent infections established after challenge was significantly reduced. Phosphonoacetic acid treatment of the primary mutant-induced infection abolished the protection against reinfection with parental virus. Acyclovir treatment of the primary infection with the mutant virus did not affect the protection against reinfection with parental virus. The results indicate that drug-resistant, latency-negative, HSV mutants are a promising starting point for the development of an attenuated HSV vaccine. PMID- 6251785 TI - Electron microscope study of cultured cells of the chorioallantoic membrane infected with representative paramyxoviruses. AB - Chorioallantoic membrane (CAM) tissue cultures were found to be permissive for representative paramyxoviruses. The CAM cells can be used for plaque assay without the presence of trypsin. Ultrastructures of CAM cells infected with paramyxovirus Yucaipa (PMY), Sendai virus, and NDV were different. Nucleocapsids were readily seen in budding structures of cells infected with PMY, and in Sendai virus infected cells, large clusters of nucleocapsids were clearly evident in the cytoplasm. The site of glycoprotein cleavage does not have any effect on the nature of budding. It appears that a factor or factors in addition to the nature of the plasma membrane influences the morphology of cells infected with paramyxoviruses. PMID- 6251786 TI - DNA of simian virus 40 mutates Chinese hamster cells. AB - Infection of Chinese hamster cells with SV 40 DNA gives rise to mutants resistant both to S-axaguanine (AG) and aminopterin (AP). This mutagenic effect can be raised when facilitating DNA uptake of cells by a helper agent. The extent of muyagenic action depends further on the concentration of DNA applied to the cells, with 2 micrograms/ml being more effective than 10 micrograms/ml, as well as on the period of incubation of infected cells before onset of mutant selection (mutation expression time). Using the AG resistance marker the mutation frequency can be increased more than 8-fold compared with the spontaneous mutation frequency. Reconstituted SV 40 minichromosomes show a mutagenic action which is similar to the DNA-mediated mutagensis whereas non-viral DNA from mammalian cells fails to induce mutations significantly. A major part of isolated clones of SV 40 induced mutants tested so far does express SV 40 T-antigen, suggesting the persistence of SV 40 genetic material in these clones. The possible existence of relations between mutagenic and transforming capacities of SV 40 is discussed. PMID- 6251787 TI - Experimental infection and the state of viral latency of adult tupaia with herpes simplex virus type 1 and 2 and infection of juvenile Tupaia with temperature sensitive mutants of HSV Type 2. AB - The susceptibility of adult Tupaia Belangeri to infection with herpes simplex virus (HVS) was investigated. Adult animals were inoculated intraperitoneally with HSV type 1 or 2. With the exception of HSV-2, strain HG-52, 10(5)--10(6) PFU of all HSV strains caused lethal infection irrespective of the age of the animals. Infections HSV was recovered from the spinal cord of those animals which had survived infection with a low dose of virus. The DNA of the recovered viruses was compared to the DNA of the inoculated HSV. The viral genome of the recovered HSV was unchanged as judged by analysis of the fragment pattern of the viral DNA's using restriction endonucleases. Animals which had survived the first HSV infection were protected against a second infection even at highly lethal doses of HSV-1 or 2. Juvenile Tupaia survived infection with temperature-sensitive mutants of HSV-2, strain HG-52, which induced protection against a second infection with lethal doses of HSV-1 or 2. PMID- 6251788 TI - Epstein-barr Virus (EBV) intracellular antigens: factors affecting the patterns of immunofluorescence. AB - Immunofluorescent pictures of Epstein-Barr Virus (EBV) antigens were studied with regard to the lability of the antigens to heat and to solvents as well as to the modifications of the immunofluorescent patterns related to the length of drying time of the cell smears. The nuclear antigen (EBNA) and the early restricted antigen (EA-R) appeared to be sensitive to heating 30 minutes at 56 degrees C. Lengthening of the drying time of the cell smears results in a progressive dispersion of three antigens; viral capsid antigen (VCA), early diffuse antigen (EA-D) and EA-R in the cell and in some apparent loss of EBNA. Petroleum benzine which can be used as a fixative on plastic, support, allows the detection of all four antigens. PMID- 6251789 TI - [Pathomorphology and mineral saturation of the bone tissue in congenital vitamin D-resistant rickets]. AB - Fragments of tubular bones obtained in correcting operations from 11 patients aged between 10 and 17 years with congenital vitamin-D-resistant rickets were examined using quantitative microroentgenography, light and electron microscopy. The bone tissue was characterized by reduced mineral saturation of microstructures, marked osteoporosis and numerous resorption foci. The latter were located around osteocytes both in the area of osteones and in inserted plates. Electron microscopy revealed uneven incrustation of the organic matrix with the mineral component as well as disorganization of the ultrastructure of collagen fibrills and associated crystals in the foci of periosteocyte resorption. PMID- 6251790 TI - In vivo and in vitro models of demyelinating diseases. III. JHM virus infection of rats. AB - Suckling rats of three inbred and three outbred strains were inoculated intraperitoneally (P) or intracerebrally (IC) with the JHM strain of mouse hepatitis virus (JHMV) and were monitored for evidence of neurologic diseases. Consequences of varying age at inoculation, route of injection, and virus dose were ascertained. No disease was evident after IP injection but IC inoculation with at least 10(4) plaque-forming units at 2 days of age resulted in either a rapidly fatal encephalitis or a chronic, progressive, fatal neurologic disease in most rats, regardless of strain. Inoculation at 5 or 10 days of age predominantly caused the chronic neurologic disease, characterized by demyelinating lesions in the brain, spinal cord, or optic nerve, which sometimes were evident as late as several months postinoculation. Demyelination in the optic nerve proved to be concurrent with demyelinating lesions elsewhere in the CNS. Occasionally, clinical remissions were observed in rats in which posterior paralysis developed, suggesting that remyelination in the rat can occur. Demonstration of virus replication, by infectivity, in rats exhibiting neurologic disease and in rats without clinical symptoms was substantiated by electron microscopic observations of virus development and assembly in oligodendroglia of the optic nerve and spinal cord. In view of the protracted course of the disease in some rats, presence of demyelinating lesions confirmed by light and electron microscopy, and remissions of clinical symptoms, the JHMV-infected rat seems to be an appropriate animal model to study virus-mediated progressive demyelinating disease. PMID- 6251792 TI - Strain specificity of clinical isolates of herpes simplex virus. AB - Herpes simplex virus (HSV) produces a wide variety of ocular disease in man. Although host factors are important in determining this variation, it is possible that the different clinical patterns of herpetic ocular disease may be attributed at least partially to the differing biological behavior of specific strains of HSV. To test this theory, we compared the anterior segment disease produced by infecting rabbit corneas with seven different strains of HSV. We found that these seven different strains produced different patterns of ocular disease in the rabbit eye. This also may occur in humans, and we hope to define the biological differences that cause one strain to produce disease more severe than that produced by another strain. PMID- 6251791 TI - Progressive multifocal leukoencephalopathy: immunofluorescent demonstration of simian virus 40 antigen in CSF cells and response to cytarabine therapy. AB - We report an instance of progressive multifocal leukoencephalopathy in which cytarabine administration was successful as demonstrated by clinical course and follow-up computerized tomography studies. In this case, simian virus 40 (SV40) antigen was demonstrated in CSF cells by the indirect immunofluorescence technique. PMID- 6251793 TI - Cataract formation. PMID- 6251794 TI - A comparison of treatment modalities in carcinoma of the maxillary antrum. AB - Sixty-two patients with carcinoma of the maxillary antrum are observed to define symptoms, physical findings, and radiologic findings suggestive of a poor prognosis. Using these poor prognostic indicators, the cases are retrospectively analyzed according to the various treatment modalities that were used. It is concluded from the accumulated data that raesection of the orbital contents can be avoided in selected patients with T3 and T4 carcinoma of the paranasal sinuses. PMID- 6251795 TI - Radical surgery for ethmoid cancer. AB - Radical surgery followed by radiotherapy offers the best chance of cure for ethmoid cancer. In operations on 15 patients with ethmoid cancer, intracranial spread was found in five instances. In every patient, a craniofacial ethmoidectomy was performed. Two approaches are recommended. If there is radiologic or clinical evidence of intracranial spread, a frontal craniotomy and lateral rhinotomy approach is employed. With the help of the neurosurgeon, the overlying dura can be resected with the anterior cranial floor. When the cribriform plate appears intact, the resection is accomplished via a lateral rhinotomy and transfrontal sinus approach to the anterior cranial fossa. These techniques were used in 15 patients. Nine are free of recurrence after an observation time of two to seven years. PMID- 6251796 TI - Regional odontodysplasia. AB - A case of regional odontodysplasia is reported. An unusual feature, only twice previously described in the world literature of fifty-four cases, was the presence of an apparently normal tooth within the group of affectd teeth. The implications of such a finding for the various theories relating to aetiology and pathogenesis are discussed. PMID- 6251797 TI - Calcium stimulation of a novel lipoxygenase. PMID- 6251798 TI - Disappearance of a basic chromosomal protein from cells of a mouse temperature sensitive mutant defective in histone phosphorylation. PMID- 6251799 TI - Human erythrocyte phosphoglycerate mutase: evidence for normal catalysis in the absence of added 2,3-bisphospho-D-glycerate. PMID- 6251800 TI - Conversion of monensin from an ionophore to an inhibitor of Na+ uptake by SV3t3 membrane vesicles as a function of Na+ concentration. PMID- 6251801 TI - Modified polynucleotides. V. Slow-down of nuclease action by 5-alkyluracil containing DNAs. PMID- 6251802 TI - Decrease by glucagon in hepatic succinyl-CoA. PMID- 6251803 TI - Prostaglandin metabolism in the rat adrenal cortex: characterization of prostaglandin-9-ketoreductase and 15-hydroxyprostaglandin dehydrogenase. PMID- 6251804 TI - Distribution of stereospecific opiate receptor binding activity between subcellular fractions from ovine corpus striatum. PMID- 6251805 TI - Photoaffinity spin-labeling of the Ca2+ ATPase in sarcoplasmic reticulum: evidence for oligomeric structure. PMID- 6251806 TI - Suppression of cyclic AMP-dependent protein kinase activity in murine melanoma cells by 12-0-tetradecanoylphorbol-13-acetate. PMID- 6251807 TI - Apparent "negative cooperativity" kinetics in the absence of a nonlinear Scatchard plot of thyrotropin-receptor interaction in a human thyroid adenoma. PMID- 6251808 TI - Release of calcium from membranes and its relation to phagocytotic metabolic changes: a fluorescence study on leukocytes loaded with chlortetracycline. PMID- 6251809 TI - Protection by picolinamide, a novel inhibitor of poly (ADP-ribose) synthetase, against both streptozotocin-induced depression of proinsulin synthesis and reduction of NAD content in pancreatic islets. PMID- 6251810 TI - Stimulation of synaptic membrane phosphorylation by a calcium and calmodulin independent heat stable cytosol factor. PMID- 6251811 TI - Isolation of bovine cytochrome c1 as a single non-denatured subunit using gel filtration or high pressure liquid chromatography in deoxycholate. PMID- 6251812 TI - Tubulin polymerisation in the presence of GMP-PCP. PMID- 6251813 TI - Hormonal stimulation of cAMP-dependent protein kinase in rat pancreas. PMID- 6251814 TI - Studies of the internalization of vitamin D3 metabolites by cultured osteogenic sarcoma cells and their application to a non-chromatographic cytoreceptor assay for 1,25-dihydroxyvitamin D3. PMID- 6251815 TI - Inhibition of Na+, K+-ATPase of intact mouse soleus muscle by Mg++. PMID- 6251816 TI - Cyclic AMP-dependent protein kinase of Neurospora crassa. PMID- 6251817 TI - Enzymatic dephosphorylation of dolichyl pyrophosphate--the bacitracin-sensitive, rate-limiting step for dolichyl mannosyl phosphate synthesis in rat liver microsomes. PMID- 6251818 TI - Stimulation of insulin secretion from mouse pancreatic islets, maintained in tissue culture, by the pituitary neurointermediate lobe of the genetically obese mouse (ob/ob). PMID- 6251820 TI - Specific thyroxine receptors in mammary cytosol from lactating cattle. PMID- 6251819 TI - Serine protease inhibitors inhibit superoxide production by human basophils stimulated by anti-IgE. PMID- 6251821 TI - In vivo replication of carcinogen-modified rat liver DNA: increased susceptibility of O6-methylguanine compared to N-7-methylguanine in replicated DNA to S1-nuclease. PMID- 6251822 TI - Characterization of a distinct membrane bound dipeptidyl carboxypeptidase inactivating enkephalin in brain. PMID- 6251823 TI - Aggregation of human lymphoblastoid cells by tumor-promoting phorbol esters and dihydroteleocidin B. PMID- 6251824 TI - Differences in aminoacylation in vivo and in vitro of lysine isoaccepting tRNAs from virus-transformed cells. PMID- 6251825 TI - Acetylcholine-induced receptor-controlled ion flux investigated by flow quench techniques. PMID- 6251827 TI - Purification of rat heart cyclic nucleotide phosphodiesterase on column of immobilized phenylbutenolide inhibitor. PMID- 6251826 TI - Reduction of LH-RH pituitary and estradiol uterine binding sites by a superactive analog of luteinizing hormone-releasing hormone. PMID- 6251828 TI - Effect of experimental diabetes on glycolytic intermediates and regulation of phosphofructokinase in rat lens. PMID- 6251829 TI - Dethiophosphorylation of thiophosphorylase a by a multifunctional phosphoprotein phosphatase of Mr=35,000. PMID- 6251831 TI - Timing of ubiquitin synthesis and conjugation into protein A24 during the HeLa cell cycle. PMID- 6251830 TI - Independent responses of nucleoside triphosphatase and protein kinase activities in nuclear envelope following thioacetamide treatment. PMID- 6251832 TI - Molecular cloning of part of the mitochondrial DNA of Drosophila melanogaster. PMID- 6251833 TI - The isolation of a restriction enzyme from Bordetella pertussis. PMID- 6251834 TI - An adenine nucleotide translocase in the procaryote Methanobacterium thermoautotrophicum. PMID- 6251835 TI - Arrest of mammary tumor growth in vivo by L-arginine: stimulation of NAD dependent activation of adenylate cyclase. PMID- 6251836 TI - The nucleotide sequence of nuclear 4.8S RNA of mouse cells. PMID- 6251837 TI - Identification of a phi X174 coded protein involved in the inhibition of beta galactosidase synthesis in Escherichia coli. PMID- 6251839 TI - Control of ribosomal protein phosphorylation in HeLa cells. PMID- 6251840 TI - ESR evidence of superoxide radical dismutation by human ceruloplasmin. PMID- 6251838 TI - Studies on the mechanism of activation of mitotic histone H1 kinase. PMID- 6251841 TI - Fibroblasts transformed by an oncogenic virus show decreased uptake of puromycin aminonucleoside. PMID- 6251842 TI - Resistance of cells biochemically transformed by herpes simplex virus DNA fragments to thymidine and deoxyadenosine cytotoxicity. PMID- 6251843 TI - Conformational studies of lipid-bound polypeptides by elucidation of proton proton cross-relaxation networks. PMID- 6251844 TI - Intrinsic coupling in cytochrome oxidase: nature and stoichiometry of the coupling reactions. PMID- 6251845 TI - Energized transport of cations by cytochrome oxidase. PMID- 6251846 TI - Regulation of fluid secretion by calcium-dependent modulator proteins of 3':5' cyclic-AMP phosphodiesterase. PMID- 6251848 TI - Isolation and characterization of (Na,K)-ATPase proteolipid. PMID- 6251847 TI - The isolation and characterization of an active site phosphohistidine peptide from human erythrocyte bisphosphoglycerate synthase. PMID- 6251849 TI - Probing the biologically and immunologically active conformation of beta endorphin: studies on C-terminal deletion analogs. PMID- 6251850 TI - Corticotropin-like substances in human gastric antrum and pancreas. PMID- 6251851 TI - Biosynthesis of cytoplasmic subunits of cytochrome C oxidase in rat liver. PMID- 6251852 TI - Purification of luteinizing hormone receptor and its subunit structure. PMID- 6251853 TI - Presence of methyl adenine in the DNA of some strains of Neisseria gonorrhoeae. PMID- 6251854 TI - Phosphatidylcholine mobility in bile salt depleted rat liver microsomes. PMID- 6251855 TI - Human neutrophil elastase functions as a type III collagen "collagenase". PMID- 6251856 TI - Correlation between anti-RANA and anti-EBNA titers in normal subjects with and without HLA-DRw4. AB - We have determined the relationship of antibody titers to the rheumatoid arthritis nuclear antigen (RANA) and of antibody titers to the Epstein-Barr nuclear antigen (EBNA) to each other and to the DRw4 B cell alloantigen in the sera of 34 normal white adults. By a sensitive indirect immunofluorescence (IF) assay, 76% had RANA antibody, compared to 23% by a micro-immunodiffusion assay. The correlation coefficient for the tube dilution titers of anti-RANA and anti EBNA was 0.61 (P < 10(-4)). The 14 DRw4-positive subjects and the 20 DRw4 negative subjects did not differ with respect to anti-RANA titers (P = 0.51) or anti-EBNA titers (P = 0.89). We conclude that: 1) most normal adults have RANA antibody by IF; 2) anti-RANA and anti-EBNA titers are closely related; 3) the titers of these antibodies cannot be related to the presence of the DRw4 determinant in normal persons. PMID- 6251857 TI - Differences in the lipolytic and cyclic AMP accumulative action of noradrenaline theophylline and norephedrine-theophylline. AB - The action of theophylline derivatives (-)-7-2-(2-hydroxy-1-methyl-2-phenyl ethylamino)-ethyl-theophyl-line (cafedrine) and 7-2-2-(3,4-dihydroxy-phenyl-2 hydroxy-ethylamino)-ethyl-theophylline (theodrenaline) on free fatty acids (FFA) levels in rat blood serum and on cyclic AMP (cAMP) accumulation and FFA mobilization in isolated fat cells has been studied and compared to the action of a noradrenaline plus aminophylline mixture (NAA). A significant in vivo increase of FFA appeared 15 min after NAT and 90 min after NET i.p. administration. NAA was active at both times. Unlike NET, NAT stimulated in vitro FFA mobilization and cAMP accumulation: NAA action was however stronger. NAT-mediated cAMP accumulation, but not that which was NAA-induced, was totally inhibited by timolol. Our results suggest the existence of a beta-adrenergic mechanism for NAT and a tyraminic mechanism for NET. A theophyllinic action dos not seem to apply to either drug. PMID- 6251858 TI - Pharmacological study of 2-phosphonoxybenzoic acid (fosfosal), a new analgesic drug. PMID- 6251859 TI - Variations in dose and time of collagenase digestion for maximal islet cell separation for transplantation. PMID- 6251860 TI - The nutritive value of silages. Digestion of organic matter, gross energy and carbohydrate constituents in the rumen and intestines of sheep receiving diets of grass silage or grass silage and barley. AB - 1. Two experiments were conducted to study the digestion of organic matter, gross energy and carbohydrate constituents in the rumen, small intestine and caecum and colon of sheep given grass silage diets. Three silages made from perennial ryegrass (Lolium perenne) with formic acid as an additive were used. One was made from first-harvest grass in the spring and the others from regrowth grass cut from a single sward in either early autumn or late autumn. Expt 1 involved a comparison between the spring silage given alone or supplemented with barley (silage:barley, 4:1 dry matter (DM) basis). Expt 2 involved a comparison between the early-cut and late-cut autumn silages. 2. In Expt 1, supplementation of the silage with barley resulted in a non-significant (P > 0.05) reduction in the proportion of digestible energy (DE) and digestible organic matter digested in the rumen and an increase in the proportions digested in the small intestine. There were also pronounced effects of barley on ruminal cellulolysis and the proportion of digestible cellulose broken down in the rumen was reduced (P < 0.05) from 0.90 to 0.77. There was an increased passage of alpha-linked glucose polymers to the duodenum but even with the supplemented diet 0.91 of the dietary polymers were digested in the rumen. The molar proportion of propionic acid in the rumen tended to be reduced and there were increases in the proportions of butyric acid (P < 0.01) and acetic acid. 3. Expt 2, the digestibility of organic matter, gross energy and cellulose in the early-cut silage was higher (P < 0.01) than in the late-cut silage but there were no significant (P < 0.05) differences between silages in sites of digestion of these constituents. However, the molar proportion of acetic acid in the rumen was higher (P < 0.01) and the molar proportion of propionic acid was lower (P < 0.01) with the late-cut silage than the early-cut silage. 4. The results are discussed in relation to the voluntary intake and utilization of high-digestibility silages. PMID- 6251861 TI - Dependence of thyroxine utilization rate on dietary composition. AB - 1. The rate of utilization (k) of labelled thyroxine increased when energy intake, given as standard pig meal, was doubled from 20 to 40 g/kg body-weight per d. When the bulk of food was increased, but not its energy content, the value of k did not change. Ambient temperature was constant throughout the experiment. 2. Groups of pigs were given pig meal at 20 g/kg body-weight, 40 g/kg body-weight or 20 g/kg body-weight plus a supplement. The supplement was of equivalent energy content to 20 g pig meal/kg body-weight and consisted of coconut (high-fat), fish meal (high-protein) or glucose. The values of k were similar on diets (g/kg body weight) of 40 pig meal, 20 pig meal plus coconut, and 20 pig meal plus fish meal. When the supplement was glucose however the values of k were similar to that for 20 g pig meal/kg body-weight. 3. The plasma concentrations of T4, and triiodothyronine were not affected by eating a meal, or by changing the energy intake presented as pig meal. A comparison between pigs given 20 g pig meal/kg body-weight plus supplements of bran, coconut, fish meal or glucose revealed differences in the concentration of both hormones. When food was withdrawn for 5 d the concentrations of both hormones declined. PMID- 6251862 TI - The response of serum 25-hydroxyvitamin D concentrations to vitamin D intake and insolation in sheep. AB - 1. Vitamin D-depleted, housed sheep were given diets providing fixed intakes of cholecalciferol ranging from 0.0 to 0.8 microgram/kg body-wt per d for 220 d. Thereafter they were shorn, deprived of dietary cholecalciferol and turned out from 30 June to 30 November. The concentration of 25-hydroxyvitamin D (25-OHD) in serum was determined at frequent intervals. 2. The serum concentrations of 25-OHD took approximately 10 weeks to stabilize after which they reflected dietary intake over 0.1--0.4 microgram/kg body-wt per d. For intakes of 0.4 and 0.8 microgram/kg body-wt per d the mean maximum concentrations were similar, but the rates of increase differed. The latter was proportional to the logarithm of intake over the range studied. 3. Changes in serum 25-OHD due to insolation were similar in all sheep regardless of their starting values, and consequently in some animals reached levels considerably greater than from the dietary source. 4. Although the response of serum 25-OHD to the higher dietary intakes appeared to be limited there was no evidence of any such control over the response ot endogenously-synthesized vitamin. PMID- 6251863 TI - Rates of thiol-disulfide interchange reactions involving proteins and kinetic measurements of thiol pKa values. AB - Bronsted coefficients have been determined for the rates of thiol-disulfide interchange between low molecular weight thiols and the disulfide groups of four native or modified proteins: DNase (beta nuc congruent to 0.36), lysozyme (beta nuc congruent to 0.55), adenylate kinase(SSCH3)2 (beta nuc congruent to 0.65), and papain(SSCH3) (beta nuc congruent to 0.45). These values are similar to those observed for reductions of oxidized glutathione and Ellman's reagent by a similar set of thiols (beta nuc congruent to 0.5). Glutathione is anomalously slow in reduction of certain protein disulfide groups: although this effect may in part reflect steric hinderance to attack by the relatively large glutathione molecule at disulfides shielded by protein tertiary structure, other (presently undefined) factors appear also to be important, at least in the case of DNase. The rates of reduction of several disulfide derivatives of papain(SSR) by DTT were determined. These data provide estimates of the Bronsted coefficient for the "central" thiol in thiol-disulfide interchange: these estimates fall in the range beta c congruent to -0.25 to -0.43. Rates of reduction of protein disulfide moieties were analyzed by using a Bronsted equation developed previously [Szajewski, R. P., & Whitesides, G. M. (1980) J. Am. Chem. Soc. 102, 2011] to yield pKa values for the participating thiol moieties: in particular, for papain, pKa(Cys-25) = 8.4 at pH 9 and pKa (Cys-25) = 4.1 at pH 6. The thiols of the structurally essential cysteine group of lysozyme seem to have pKa congruent to 11. The advantages and disadvantages of this method for estimating thiol pKa values are discussed. PMID- 6251864 TI - Binding of arylazidocytochrome c derivatives to beef heart cytochrome c oxidase: cross-linking in the high- and low-affinity binding sites. AB - Two arylazidocytochrome c derivatives, one modified at lysine-13 and the second modified at lysine-22, were reacted with beef heart cytochrome c oxidase. The lysine-13 modified arylazidocytochrome c was found to cross-link both to the enzyme and with lipid bound to the cytochrome c oxidase complex. The lysine-22 derivative reacted only with lipids. Cross-linking to protein was through subunit II of the cytochrome c oxidase complex, as first reported by Bisson et al. [Bisson, R., Azzi, A., Gutweniger, H., Colonna, R., Monteccuco, C., & Zanotti, A. (1978) J. Biol. Chem. 253, 1874]. Binding studies show that the cytochrome c derivative covalently bound to subunit II was in the high-affinity binding site for the substrate. Evidence is also presented to suggest that cytochrome c bound to the lipid was in the low-affinity binding site [as defined by Ferguson-Miller et al. [Ferguson-Miller, S., Brautigan, D. L., & Margoliash, E. (1976) J. Biol. Chem. 251, 1104]]. Covalent binding of the cytochrome c derivative into the high affinity binding site was found to inhibit electron transfer even when native cytochrome c was added as a substrate. Inhibition was almost complete when 1 mol of the Lys-13 modified arylazidocytochrome c was covalently bound to the enzyme per cytochrome c oxidase dimer (i.e., congruent to 280 000 daltons). Covalent binding of either derivative with lipid (low-affinity site) had very little effect on the overall electron transfer activity of cytochrome c oxidase. These results are discussed in terms of current theories of cytochrome c-cytochrome c oxidase interactions. PMID- 6251865 TI - Reaction of cytochrome c oxidase with endogenous and exogenous cytochrome c. PMID- 6251866 TI - Biogenesis of mitochondria. oli2 Mutations affecting the coupling of oxidation to phosphorylation in Saccharomyces cerevisiae. AB - 1. Two oligomycin-resistant strains of Saccharomyces cerevisiae have been isolated and shown to have mutations in the oli2 region of the mitochondrial DNA. On solid media containing a non-fermentable energy source, the mutant strains were able to grow only slowly at 28 degrees C and not at all at 18 degrees C or 36 degrees C. 2. When grown in a glucose-limited chemostat at 28 degrees C, the mutant strains were almost completely defective in oxidative metabolism. The mutant mitochondria contained significant levels of all respiratory enzymes, and an active, oligomycin-sensitive ATPase, but the ATP-32Pi exchange activity and P : O ratio were very low. 3. The mutations in these strains are genetically closely linked to mit mutations which have been shown to affect a 20 000-dalton ATPase subunit (Roberts, H., Choo, W.M., Murphy, M., Marzuki, S., Lukins, H.B. and Linnane, A.W. (1979) FEBS Lett. 108, 501-504). Since the mitochondrial ATPase in these mutant strains appears to be fully assembled, the defect in the coupling mechanism is probably a result of a small alteration in the structure of the 20 000-dalton ATPase subunit. 4. When the mutant strains were grown at 18 degrees C, the mitochondria had very low cytochrome oxidase activities, and reduced levels of cytochrome aa3. The largest subunit (Mr 40 000) of this enzyme was not synthesized. PMID- 6251867 TI - The role of the Rieske iron-sulfur center as the electron donor to ferricytochrome c2 in Rhodopseudomonas sphaeroides. AB - The Rieske iron-sulfur center in the photosynthetic bacterium Rhodopseudomonas sphaeroides appears to be the direct electron donor to ferricytochrome c2, reducing the cytochrome on a submillisecond timescale which is slower than the rapid phase of cytochrome oxidation (t 1/2 3-5 microseconds). The reduction of the ferricytochrome by the Rieske center is inhibited by 5-n-undecyl-6-hydroxy 4,7-dioxobenzothiazole (UHDBT) but not by antimycin. The slower (102 ms) antimycin-sensitive phase of ferricytochrome c2 reduction, attributed to a specific ubiquinone-10 molecule (Qz), and the associated carotenoid spectral response to membrane potential formation are also inhibited by UHDBT. Since the light-induced oxidation of the Rieske center is only observed in the presence of antimycin, it seems likely that the reduced form of Qz (QzH2) reduces the Rieske Center in an antimycin-sensitive reaction. From the extent of the UHDBT-sensitive ferricytochrome c2 reduction we estimate that there are 0.7 Rieske iron-sulfur centers per reaction center. UHDBT shifts the EPR derivative absorption spectrum of the Rieske center from gy 1.90 to gy 1.89, and shifts the Em,7 from 280 to 350 mV. While this latter shift may account for the subsequent failure of the iron sulfur center to reduce ferricytochrome c2, it is not clear how this can explain the other effects of the inhibitor, such as the prevention of cytochrome b reduction and the elimination of the uptake of HII(+); these may reflect additional sites of action of the inhibitor. PMID- 6251868 TI - The kinetics and thermodynamics of the reduction of cytochrome c by substituted p benzoquinols in solution. AB - 1. The mechanisms by which p-benzoquinol and its derivatives reduce cytochrome c in solution have been investigated. 2. The two major reductants are the species QH- (anionic quinol) and Q.- (anionic semiquinone). A minor route of electron transfer from the fully protonated QH2 species can also occur. 3. The relative contributions of these routes to the overall reduction rate are governed by pH, ionic strength and relative reactant concentrations. 4. For a series of substituted p-benzoquinols, the forward rate constant, k1, of the anionic quinol mediatd reaction is related to the midpoint potential of the QH-/QH. couple involved in the rate-limiting step, as predicted by the theory of Marcus for outer-sphere electron transfer reactions in a bimolecular collision process. 5. A mechanism for the biological quinol oxidation reactions in mitochondria and chloroplasts is proposed based upon the findings with these reactions in solution. PMID- 6251869 TI - Interaction of cytochrome c with cytochrome bc1 complex of the mitochondrial respiratory chain. AB - The binding of cytochrome c to the cytochrome bc1 complex of bovine heart mitochondria was studied. Cytochrome c derivatives, arylazido-labeled at lysine 13 or lysine 22, were prepared and their properties as electron acceptors from the bc1 complex were measured. Mixtures of bc1 complex with cytochrome c derivatives were illuminated with ultraviolet light and afterwards subjected to polyacrylamide gel electrophoresis. The gels were analysed using dual-wavelength scanning at 280 minus 300 and 400 minus 430 nm. It was found that illumination with ultraviolet light in the presence of the lysine 12 derivative produced a diminution of the polypeptide of the bc1 coplex having molecular weight 30 000 (band IV) and formation of a new polypeptide composed of band IV and cytochrome c. Band IV was identified as cytochrome c1, and it was concluded that this hemoprotein interacts with cytochrome c and contains its binding site in complex III of the mitochondrial respiratory chain. Illumination of the bc1 complex in presence of the lysine 22 derivative did not produce changes of the polypeptide pattern. PMID- 6251870 TI - Purification and characterization of cytochrome f-556.5 from the blue-green alga Spirulina platensis. AB - The membrane-bound cytochrome f-556.5 from the blue-green alga Spirulina platensis was purified to apparent homogeneity. Most of its properties are comparable to cytochrome f isolated from higher plants and green algae. It is clearly distinguishable from soluble cytochrome c-554, also present in Spirulina, which probably replaces the function of plastocyanin in photosynthetic electron transport. 1. The reduced form of cytochrome f exhibits an asymmetrical alpha band with a maximum at 556.5 nm, and a pronounced shoulder at 550 nm. The beta-, gamma and delta-bands coincide with those described for Scenedesmus cytochrome f 553, with maxima at 524 (532), 422, 331 and a protein peak at 276 nm. The maximum of ferricytochrome f is at 410.5 nm; there is no indication of a weak 695 nm band, described for soluble c-type cytochromes. The purest preparations had a delta/protein-peak ratio of 0.8; the gamma/alpha ratio was 7.3. Formation of a pyridine hemochromogen with a maximum at 550 nm indicated a c-type cytochrome. The molar extinction coefficient at 556.5 nm is 30200, the differential extinction coefficient 21 500. 2. The molecular weight determined by gel filtration or SDS-polyacrylamide gel electrophoresis is 33 000 and 34 000, respectively. 3. The redox properties differ from those described for other cytochromes f isolated from green algae and higher plants: the midpoint redox potential is significantly more negative (+318 mV, pH 7.0) and from pH 6 to 10 no pH dependence is observed. 4. The isoelectric point was determined at pH 3.95, which is more acidic as compared to other cytochromes f. 5. Comparison of the amino acid composition indicated a distant relationship to higher plant cytochrome f and a closer relationship to cytochrome f from green algae. PMID- 6251871 TI - Metabolic regulation by pH gradients. Inhibition of photosynthesis by indirect proton transfer across the chloroplast envelope. AB - Anions of several weak acids inhibited photosynthesis in isolated spinach chloroplasts. Inhibition was drastic at low pH and weak or absent at high pH. Glyoxylate was particularly effective and inhibition decreased in the order: glyoxylate, nitrite, glycerate, formate, hydroxypyruvate, glycolate, propionate, acetate, pyruvate. These anions operated as indirect proton shuttles across the chloroplast envelope. They compensated active proton fluxes into the medium, minimized gradients in proton activity across the chloroplast envelope, and so prevented light-dependent stroma alkalization. This caused inhibition of sugar bisphosphatases which are known to be pH-regulated. At concentrations that caused potosynthesis inhibition, the proton shuttles were not effective in decreasing the proton gradient across the thylakoids. Some anions also inhibited fructose bisphosphatase directly, when present at concentratins higher than needed for photosynthesis inhibition. PMID- 6251872 TI - Kinetic, binding and ultrastructural properties of the beef heart adenine nucleotide carrier protein after incorporation into phospholipid vesicles. AB - 1. ADP/ATP transport has been reconstituted by incorporation of the purified carrier protein in liposomes filled with ATP. The transport was assayed by uptake of [14C]ADP into the liposomes, and by release of ATP as determined by a luminescence technique. [14C]ADP uptake was strictly dependent on internal ATP. 2. The simplest phospholipid system capable of yielding high rates of ADP/ATP transport was a mixture of phosphatidylethanolamine and cariolipin (92: 8, w/w). 3. ADP/ATP transport in the reconstituted system proceeded by exchange-diffusion with a 1/1 stoichiometry. The specificity for aDP and ATP was absolute. The capacity and the rate of exchange depended on the concentration of ATP present in liposomes. The rate of transport at 20 degrees C, at 20 mM internal ATP, routinely ranged between 300 and 1000 nmol of nucleotide exchanged per min/mg of added carrier protein. The apparent Km value for external ADP was around 10 microM. 4. The ADP/ATP exchange in the reconstituted system was rather stable to ageing. It dropped by only 20% after 1 day of ageing at 20 degrees C. Divalent cations (Mg2+, Mn2+, Ca2+) at concentrations higher than 1 to 2 mM had a deleterious effect on ADP/ATP transport, concomitant with the release of internal ATP and accumulation of multilamellar vesicles. 5. Atractyloside behaved as a competitive inhibitor and carboxyatractyloside as a non-competitive inhibitor. Bongkrekic acid required a slightly acidic pH to be inhibitory. The data concerning atractyloside, carboxyatractyloside and bongkrekic acid were similar to those obtained with whole mitochondria, suggesting that the carrier protein in liposomes has the same asymmetrical arrangement as in the mitochondria. 6. The percentage of competent carrier protein in liposomes was calculated from dose response data concerning the inhibition of ADP/ATP transport by atractyloside or carboxyatractyloside, and from the amount of bound [3H]-atractyloside removable by ADP. By both methods, 3 to 6% of the added carrier protein was found to be competent in ADP/ATP transport, based on the assumption that the binding of one atractyloside or carboxyatractyloside molecule per 30000 molecular weight carrier unit results in complete inhibition of transport. 7. Freeze-fracture electron microscopy showed that the ADP/ATP carrier protein-lipid preparations are formed by small vesicles, most of which give rise to smooth fracture faces (probably pure lipid vesicles). Only a small percentage of the vesicles (2 to 4% depending on the amount of carrier protein added) were clearly particulated. About 90% of the particulated vesicles showed no more than 2 particles per vesicle and only 5% more than 5 particles per vesicle. The distribution of the particles between convex and concave fracture faces was asymmetric; about 2/3 of the protein molecules were anchored at the external surface of the vesicles and only 1/3 at the internal one... PMID- 6251873 TI - Influence of divalent cations on the reconstituted ADP, ATP exchange. AB - 1. Divalent cations cause a decrease in the exchange activity of the reconstituted ADP,ATP translocator from beef heart mitochondria. This effect is due to complex formation with the adenine nucleotides. 2. It is confirmed that only the free nucleotides are transported. A possible competition of free adenine nucleotides and the Mg2+-complexes for the binding site at the carrier protein is excluded. 3. The stability constants (Kn) for the cation-nucleotide complexes are derived from these experiments. For Mg2+-ATP, Kn = 0.8 x 10(4) M-1 and for Mg2+ ADP, Kn = 0.8 x 10(3) M-1 is obtained. 4. The carrier system was reconstituted with the neutral phospholipids phosphatidylcholine and phosphatidylethanolamine. Interaction of the divalent cations with these phospholipids seem not to be important for the exchange suppression. PMID- 6251874 TI - Blocking by 2,4,6-triaminopyrimidine of increased tight junction permeability induced by acetylcholine in the pancreas. AB - 1. The permeability of the paracellular pathway in the isolated rabbit pancreas has been studied with the aid of 2,4,6-triaminopyrimidine. 2. Addition of 2,4,6 triaminopyrimidine (1--10 mM) to the bathing medium has no effect on the rate of fluid secretion or on protein, Na+, K+, Ca2+ and sucrose concentrations in the secreted fluid. 3. When 1 x 10(-5) M carbachol is also added to the 2,4,6 triaminopyrimidine-containing bathing medium, there is a marked reduction in the increase of the paracellular permeability for sucrose and Ca2+ found upon addition of carbachol alone. The enzyme secretion, induced by carbachol, is not affected. 4. The minimal concentration of 2,4,6-triaminopyrimidine in the bathing medium required to reach its maximal effect on the paracellular permeability is approx. 0.55 mM at pH 7.4. 5. The effect of 2,4,6-triaminopyrimidine on the paracellular permeability after carbachol stimulation is also present when 2,4,6 triaminopyrimidine is added 5 min after the addition of 1 x 10(-5) M carbachol. 6. 2,4,6-Triaminopyrimidine has no effect on the increases in enzyme secretion and sucrose permeability caused by 1 x 10(-8) pancreozymin C octapeptide. 7. 2,4,6-Triaminopyrimidine appears in the secreted fluid at a concentration of 50% of that in the bathing medium. Upon addition of 1 x 10(5) M carbachol this concentration increases up to 80%. 8. These results indicate that: (a) the increased paracellular permeability upon stimulation with carbachol is not caused by the enzyme secretion as such and (b) addition of 2,4,6-triaminopyrimidine prevents the carbachol-induced increase in permeability of a channel in the tight junction complex. PMID- 6251875 TI - Leucine aminopeptidase as an echo-enzyme of polymorphonuclear neutrophils. AB - Intact polymorphonuclear neutrophils were modified chemically by a poorly permeable reagent, diazotized sulfanilic acid, and the changes in the activity of 5'-nucleotidase, alkaline phosphodiesterase, and leucine aminopeptidase were examined. Among three plasma membrane enzymes, 5'-nucleotidase activity was hardly detected in the human neutrophils. The activity of alkaline phosphodiesterase was observed in all the neutrophils examined, but was not inhibited by diazotized sulfanilic acid in the guinea-pig neutrophils. On the other hand, the activity of leucine aminopeptidase was not only found but also inhibited by diazotized sulfanilic acid without the inhibition of lactate dehydrogenase, a cytosol enzyme, in all the neutrophils, suggesting that leucine aminopeptidase is located generally on the plasma membrane as an ecto-enzyme in the neutrophils. PMID- 6251876 TI - A light scattering study on the ion permeabilities of dark-adapted bovine rod outer segment disk membranes. AB - The ion permeability properties of dark adapted bovine rod outer segment disk membranes were studied using light scattering to monitor osmotic responses of disks to various salts and ionophores. A preparation procedure is presented which provides very fresh rod outer segment material with mostly intact stacked disks, but with perforated plasma membrane. It is shown that in this preparation the disks (or rod sacs) are the only osmotically responding compartments and that these responses can be readily monitored by means of light-scattering techniques. The disk membrane is found under the conditions tested, to possess no measurable permeability to cations Na+, Ca2+, Mg2+ nor the the anions Cl-, Br-, NO3-, SO4(2 ), H2PO4- and HPO4(2-). There is a considerable K+ permeability, which can be completely abolished by millimolar amounts of divalent cations. The proton permeability of the disk membrane is found to depend dramatically upon the preparation procedure and duration. The fresher the material used the lower is the proton permeability measured. In our freshest preparations, even after freeze thawing in liquid nitrogen, the disks exhibit an H+ permeability which is so low that it cannot be measured with the techniques used in this study. Even in mitochondrial or chloroplast membmranes, in which proton gradients and therefore a low proton conductance play an essential role, such low proton permeabilities have not been found. This would suggest that proton gradients across the disk membrane could play an important role in the physiological function of the photoreceptor cell. In summary it can be said that the disk membrane, apparently more than any other natural membrane system studied so far, is capable of retaining ion gradients for extended periods of time. PMID- 6251877 TI - Spin labeling of human spectrin. Effects of temperature, divalent cations and reassociation with erythrocyte membrane. AB - Spectrin extracted from human red blood cells has been spin labeled in its dimeric and tetrameric forms with five different nitroxide derivatives of increasing chain length between their maleimide binding group and their nitroxide reporter group. Three molecules of spin label are bound per spectrin dimer. Electron spin resonance spectra show the simultaneous presence of strongly and weakly immobilized spin labels. Their relative proportion depends on the label length and is suddenly modified when it reaches 12 A This indicates the presence of cavities of approximately this size in the tertiary structure of spectrin in solution at 0 degrees C. The conformation of spectrin varies greatly with temperature. Reversible changes occur between 0 and 35 degrees C. At higher temperatures, partial denaturation is observed. Divalent cations (Mg2+ and Ca2+) stabilize spectrin in a more constrained conformation and protect it against thermal denaturation. The same behavior is observed when spin-labeled spectrin is reassociated with spectrin-depleted inside-out erythrocyte vesicles. When fatty acid spin labels are incorporated in the phospholipidic structure of these vesicles, the reassociation of spectrin does not change their electron spin resonance spectra. This result confirms the fact that spectrin interacts predominantly with proteins on erythrocyte membranes. PMID- 6251878 TI - Preparation of unilamellar liposomes of intermediate size (0.1-0.2 mumol) by a combination of reverse phase evaporation and extrusion through polycarbonate membranes. AB - Liposomes can be prepared by a combination of reverse phase evaporation and sequential extrusion through polycarbonate membranes. The vesicles have diameters in the range 0.05-0.5 micron and are mostly unilamellar as indicated by electon microscopy, capture volume, and availability of reactive groups to periodate oxidation. Sequential extrusion leads to a decrease in the encapsulation efficiency by 2-4-fold, depending upon the lipid composition. The inclusion of cholesterol at a 1 : 1 molar ratio of cholesterol-to-phospholipid increases both the mean size and the size heterogeneity of the liposomes as measured by negative stain electron microscopy. The mean size of vesicles with an equal molar ratio of cholesterol-to-phospholipid after extrusion through a 0.1 micron membrane is 0.140 micron. Vesicles composed of phosphatidylglycerol/phosphatidylcholine (1 : 4) have a mean size of 0.08 micron after extrusion through a 0.1 micron membrane. The intermediate-size (0.1-0.2 micron) vesicles formed by this process have an aqueous space-to-lipid ratio of 3 : 5 and capture between 12 and 25% of the aqueous phase. The procedure is relatively simple, rapid, and yields almost quantitative recovery of vesicles that encapsulate a large percentage of the total aqueous space. PMID- 6251879 TI - Use of cytochalasin B to distinguish between early and late events in neutrophil activation. AB - Cytochalasin B greatly enhances secretion of beta-glucuronidase and generation of superoxide on stimulation of rabbit peritoneal neutrophils with the soluble chemotactic factor N-formylmethionylleucylphenylalanine (f-Met-Leu-Phe). There are smaller changes due to cytochalasin B on binding of f-Met-Leu-[(3)H]-Phe, stimulation of phosphatidylinositol turnover and the stimulated increase in the permeability of the cell membrane to Ca(2+). These latter changes are probably artefactual and arise as secondary consequences of cell stimulation. Our observations support the notion that changes in Ca(2+) permeability of membranes and stimulation of phosphatidylinositol turnover reflect early stages in the sequence of events initiated by f-Met-Leu-Phe binding to its receptor and which lead to cell activation phenomena such as secretion and superoxide production. PMID- 6251881 TI - Photosensory transduction in the flagellated alga, Euglena gracilis. II. Evidence that blue light effects alteration in Na+/K+ permeability of the photoreceptor membrane. AB - 1. The blue light-induced cell tumbling behavior (the step-down photophobic response) and the accumulation of cells into a blue light trap (photoaccumulation) were investigated in Euglena. Dose response plots for these phenomena which we collectively term 'photobehavior' show both threshold and saturation characteristics. 2. NaCl effects apparent elevation in the photosensitivity of the cell as evidenced by alteration of the dose response plot character and lowering of the light intensity saturation level. 3. NaCl and ouabain enhance the duration of the photophobic responses and the rate of photoaccumulation. KCl and NH4Cl have lesser or inhibitory effects. 4. Choline chloride reduces the duration of the photophobic responses and the rate of photoaccumulation. 5. KCl reduces the enhancement of photobehavior induced by NaCl and at constant chloride concentration, photobehavior is unaffected by the relative KCl and NaCl concentrations. 6. Antagonists of voltage-dependent, monovalent cation fluxes in membranes (tetrodotoxin, procaine, tetraethylammonium, 4-aminopyridine) do not alter photobehavior. 7. The results suggest a role for a photoreceptor membrane-located transport system for Na+/K+ as a key step in control of the intraflagellar free Ca/+ levels that determine the photobehavior mediated by flagellar reorientation. PMID- 6251880 TI - The fluidity of plasma membranes of Dictyostelium discoideum. The effects of polyunsaturated fatty acid incorporation assessed by fluorescence depolarization and electron paramagnetic resonance. AB - Two probe techniques, fluorescence depolarization (using diphenylhexatriene) and electron paramagnetic resonance (using 5-doxyl stearic acid), have been used to assess the fluidity of the purified plasma membranes of Dictyostelium discoideum. Both techniques indicate that a large incorporation of polyunsaturated fatty acids into the plasma membranes does not significantly change membrane fluidity In addition, phosphatidylcholines isolated from cells grown on both polyunsaturated fatty acid-supplemented and unsupplemented media exhibit similar mobilities of an incorporated spin probe when dispersed in aqueous solution. This result suggests that the enrichment of a membrane already high in content of fatty acyl chains containing two double bonds with those containing three or more double bonds does not markedly change fluidity. PMID- 6251882 TI - Electron spin resonance studies of changes in membrane fluidity of Chinese hamster ovary cells during the cell cycle. AB - Electron spin resonance (ESR) spin-label methods were used with 5-doxyl-stearic acid as a probe to investigate membrane fluidity of Chinese hamster ovary (CHO) cells during the cell cycle. A 35 GHz ESR technique was developed to study membrane fluidity of intact cells. This technique requires only about 1/6 the amount of cells compared to the conventional spin-label techniques. With this technique we observed a cyclic change of membrane fluidity during the cell cycle of CHO cells: cells in mitosis had the highest membrane fluidity, whereas cells in G1 and early S phases had the lowest membrane fluidity. PMID- 6251883 TI - Isolation of sealed vesicles highly enriched with sarcolemma markers from canine ventricle. PMID- 6251884 TI - Studies on (Na+ + K+)-activated ATPase. XLVI. Effect of cation-induced conformational changes on sulfhydryl group modification. AB - (1) (Na+ + K+)-ATPase (ATP phosphohydrolase, EC 3.1.6.3) contains 34 sulfhydryl groups on the catalytic subunit, and two on the glycoprotein subunit. Under native conditions, only sulfhydryl groups on the catalytic subunit are accessible to modifying reagents. (2) The degree of inhibition of (Na+ + K+)-ATPase activity by N-ethylmaleimide and 5,5'-dithiobis(2-nitrobenzoic acid) depends on the cations present in the reaction medium. Mg2+ strongly enchances the inhibitory effects of both sulfhydryl reagents. The effects of Mg2+ on the inhibition by 5,5'-dithiobis(2-nitrobenzoic acid) are counteracted by the addition of Na+ or K+. Na+ has no more effect than choline on the inhibition by 5,5'-dithiobis(2 nitrobenzoic acid), but it enhances the inhibitory effect of N-ethylmaleimide at low Na+ concentrations (less than 10 mM). Low concentrations of K+ (less than 10 mM) slightly protect the enzyme against modification. (3) Titration of residual sulfhydryl groups reveals that these ions do not only influence modification of essential sulfhydryl groups, but also that of sulfhydryl groups which are not essential for the enzyme activity. (4) These results indicate that Na+, K+ and Mg2+ have marked effects on the conformation of the catalytic subunit of (Na+ + K+)-ATPase. Various enzyme conformations can be induced, depending on the concentration and the kind of cation added. The largest effects are observed after addition of Mg2+. PMID- 6251885 TI - Fluctuations of barrier structure in ionic channels. AB - In rate-theory analysis of ion transport in channels, the energy of binding sites and the height of activation barriers are usually considered to be time independent and not influenced by the movement of the ion. The assumption of a fixed barrier structure seems questionable, however, in view of the fact that proteins may exist in a large number of conformational states and may rapidly move from one state to the other. In this study, some of the effects of multiple conformational states of a channel on ion transport are analyzed. In the first part of the paper, the ion permeability of a channel with n binding sites is treated on the assumption that interconversion of channel states is much faster than ion transfer between binding sites. Under this condition, the form of the flux equation remains the same as for a channel with fixed barriers, provided that the rate constants for ion jumps are replaced by weighted averages over the rate constants for the individual conformational states. In the second part, a channel with two (main) barriers and a single (main) binding site is considered, with the rates of conformational transitions being arbitrary. This case, in particular, includes the situation where a jump of the ion is followed by a slow transition to a more polarized state of the binding site. Under this condition, the conductance of the channel exhibits a nonlinear dependence on ion concentration which is different from a simple saturation behavior. Under non stationary conditions damped oscillations may occur. PMID- 6251886 TI - A Ca2+-refractory state of the Ca-sensitive K+ permeability mechanism in sickle cell anaemia red cells. AB - Simultaneous measurements of Ca content and 42K+ influx in sickle cell anaemia red cells confirm predictions from earlier data in the literature that the increased Ca content of sickle cell anaemia cells which are not metabolically depleted does not cause a quinine-sensitive increase in K+ permeability. It is shown that the ionophore, A23187, can cause the Ca contained inside sickle cell anaemia cells to activate the quinine-sensitive K+-permeability mechanism. This demonstrates the existence of a Ca2+-refractory state of the K+ channel in sickle cell anaemia cells and a direct stimulatory effect of the ionophore A23187 on its Ca sensitivity. PMID- 6251887 TI - The association of tetrodotoxin-sensitive, sodium-selective ionophore of brain membranes with liposomes. AB - The tetrodotoxin-sensitive, sodsium-selective ionophore of nerve membranes has been associated with liposomes by adding the solubilized brain microsomal fraction to a cholate/phospholipid dispersion and subsequently removing the detergent from suspension by using gel chromatography. A stimulation of the efflux of sodium from the vesicles was observed in the presence of veratrine. Tetrodotoxin itself did not effect the sodium permeability, but inhibited the veratrine-induced increment. The activation was absent in the liposomes prepared without soluble membrane proteins. The effects demonstrated for tetrodotoxin and veratrine were specific for the Na+ movement. It was possible to precipitate the tetrodotoxin-sensitive ionophore by use of (NH4)2SO4. PMID- 6251888 TI - Studies on adenosine 3',5'-monophosphate phosphodiesterase of human erythrocyte membranes. AB - In this work we show the existence of cyclic AMP phosphodiesterase (EC 3.1.4.17) in human erythrocyte membranes and have clarified some properties of the enzyme. In human erythrocytes, about 23% of the total cyclic AMP phosphodiesterase activity is in a membrane-bound form. Although it could be solubilized with Triton X-100 in 5 mM Tris-HCl buffer (pH 8.0), it was not solubilized by a low or high concentration of salt. The enzyme seems to be localized in the cytoplasmic surface, since it is detected in sealed inside-out vesicles of human erythrocyte membranes, but not in intact human erythrocytes. The optimum pH was found to lie between 7.4 and 8.0, and Mg2+ was found to be necessary for its activity. Ca2+ and calmodulin could not stimulate the activity of this enzyme. Theophylline was a strong inhibitor, but cyclic GMP could not inhibit the enzymic hydrolysis of cyclic [32P]AMP and this membrane-bound enzyme therefore seems to be specific to cyclic AMP. PMID- 6251889 TI - Skin sulfhydryl oxidase. Purification and some properties. AB - A sulfhydryl-oxidizing enzyme has been found in skin of young rats and a method for purifying the enzyme over 600-fold has been developed. Enzymatic activity was assayed either by its ability to oxidize dithiothreitol of by measuring its ability to renature reductively denatured ribonuclease A. Skin sulfhydryl oxidase catalyzed the oxidation of various thiols: dithiothreitol, dithioerythritol, D penicillamine, and L-cysteine. Glutathione and 2-mercaptoethanol were very poor substrates for the enzyme. The enzyme also reactivated reductively denatured ribonuclease A, with neither the presence of a thiol nor prior reduction of the enzyme being necessary. The molecular weight of the enzyme was estimated to be 66 000 +/- 2000, and the isoelectric point was determined to be at pH 4.65. Alkylating reagents alone had some inhibiting effect on skin sulfhydryl oxidase; when the enzyme was preincubated with thiols which were substrates, inhibition by alkylating reagents was greatly increased. After preincubation with dithiothreitol, treatment of the enzyme with alkylating reagents or N ethylmaleimide caused significant inhibition; preincubation with a poor substrate, reduced glutathione, did not enhance inhibition by alkylating reagents or N-ethylmaleimide. PMID- 6251890 TI - Isolation and characterization of cyclic AMP-independent glycogen synthase kinase from rat skeletal muscle. AB - Glycogen synthase kinase was isolated from rat skeletal muscle. This kinase, which is cyclic nucleotide-independent and calcium-independent, was separated from phosphorylase kinase, cyclic AMP-dependent protein kinase and phosvitin kinase by phosphocellulose chromatography. Gel filtration on Sephadex G-100 resolved the glycogen synthase kinase into two fractions with apparent molecular weights of 68 000 (peak I) and 52 000 (peak II). This step also separated glycogen synthase kinase from the catalytic subunit of the cyclic AMP-dependent protein kinase, which had an apparent molecular weight of 39 000. Peak II glycogen synthase kinase activity was not affected by the addition of calcium, EGTA or a number of cyclic nucleotides. In addition to ATP, dATP would serve as the phosphate donor. Other trinucleotides tested were either poor or ineffective substrates. Activity was about 5-fold greater with Mg2+ than with Mn2+. Glycogen stimulated activity about 25%. Modifications of the methods of Soderling et al. ((1970) J. Biol. Chem. 245, 6317--6328) and Nimmo et al. ((1976) Eur. J. Biochem. 68, 21--30) were developed for purification of glycogen synthease (UDPglucose:glycogen 4-alpha D-glucosyltransferase, EC 2.4.1.11) to specific activity of 35 units/mg of protein. Using this preparation of glycogen synthase as substrate, the phosphorylation and inactivation catalyzed by glycogen synthase kinase was compared to that catalyzed by cyclic AMP-dependent protein kinase or phosphorylase kinase. Each of the kinases had different specificities for phosphorylation sites on glycogen synthase. PMID- 6251891 TI - Biochemical studies of the excitable membrane of Paramecium. IV. Protein kinase activities of cilia and ciliary membrane. AB - Two protein kinases (ATP: protein phosphotransferase, EC 2.7.1.37) were detected in disrupted cilia of Paramecium tetraurelia. One of the enzymes exhibited maximum activity at pH 6.0, required 4 mM Mg2+ for its maximum activity and was stimulated by cyclic AMP and cyclic GMP. Histone was a good exogenous protein substrate for this enzyme, but protamine sulfate was not. The other protein kinase showed a peak of activity at pH 8.0, required 10 mM Mg2+ for its maximum activity and was slightly inhibited by cyclic AMP and cyclic GMP. Protamine sulfate was a good exogenous substrate for this enzyme. The pH 8.0 activity partitioned preferentially with the axonemes, but the pH 6.0 activity was divided almost equally between the axonemes and the membranes. We also found indirect evidence for the presence in cilia of phosphoprotein phosphatase (phosphoprotein phosphohydrolase, EC 3.1.3.16) and adenyl cyclase (ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1) activity. PMID- 6251892 TI - Chemical modifications of Achromobacter collagenase and their influence on the enzymic activity. AB - A study of the influence of chemical modifications on the activity of Achromobacter iophagus collagenase (EC 3.4.24.8) has led to the following conclusions: a modification of 4 out of 80 COOH groups with carbodiimide led to 90% loss of enzymic activity. A 70% inactivation was found after modification of two tyrosines out of 30 with tetranitromethane. The modification of four to six tryptophans out of 16 with 2-hydroxy-5-nitrobenzyl bromide decreased enzyme activity to 36%. This inactivation is accelerated in the presence of collagen. An increase of reagent/enzyme molar ratio led to a modification of 16 tryptophan residues and denaturation of Acahromobacter collagenase. A modification of two arginines out of 18 with 1,2-cyclohexanedione and eight NH2 groups out of 24 with 2,3-dimethyl maleic anhydride does not change the collagenolytic activity. All NH2 groups become available for 2,3-dimethyl maleic anhydride after dissociation of the dimer. A possible analogy of hydrolytic site of collagenase with that of two other known bacterial metalloproteinases (thermolysin and Bacillus subtilis neutral proteinase (EC 3.4.24.4)) is discussed. PMID- 6251893 TI - Functional multiplicity of phosphoglucose isomerase from Lactobacillus casei. AB - Phosphoglucose isomerase (D-glucose-6-phosphate ketolisomerase, EC 5.3.1.9), purified from Lactobacillus casei, showed multiplicity with respect to electrophoretic mobility, molecular weight, kinetic properties and responses to erythrose 4-phosphate. Among the three forms isolated, one having a dimeric conformation, was specific for glucose 6-phosphate. Erythrose 4-phosphate inhibited this preparation in a sigmoid fashion, while this compound activated the enzyme for isomerization of ribose 5-phosphate. In tetrameric conformation of the similar subunits, the enzyme was more specific for ribose 5-phosphate and the inhibition exerted by erythrose 4-phosphate was hyperbolic. The possible implications of these observations have been discussed. PMID- 6251894 TI - Lipid activation of undecaprenol kinase from Lactobacillus plantarum. AB - Extraction of membranes of Lactobacillus plantarum with Triton X-100/glycerol solubilized up to 80% of the undecaprenol kinase activity. Fractionation of the extract by gel chromatography separated endogenous phospholipid from the enzyme but simultaneously inactivated the enzyme. The kinase was reactivated by reconstitution with various synthetic phosphatidylcholines and purified L. plantarum phospholipids. Ditetradecanoylphosphatidylcholine and lysylphosphatidylglycerol were the best activators. Furthermore, the optimal environment for enzyme stimulation was provided by different defined molar ratios of Triton X-100/phospholipid. The ratios for the phospholipids tested ranged from 1.25 to 6.3. Similar substrate specificity and kinetic constants were observed for both the solubilized and reconstituted enzymes suggesting that no fundamental changes in the enzyme activity occurred during the delipidation-reconstitution process. PMID- 6251895 TI - The intracellular distribution of high density lipoproteins taken up by isolated rat hepatocytes. AB - The subcellular distribution of 125I-labelled HDL taken up by rat hepatocytes in vivo and in vitro has been studied with subcellular fractionation techniques: differential centrifugation and isopycnic centrifugation in sucrose gradients. 125I-labelled HDL bind to plasma membranes both in vivo and in vitro and part of the membrane-bound 125I-labelled HDL can be dissociated by the addition of unlabelled HDL. The hepatocytes also internalize 125I-labelled HDL. The 125I labelled HDL accumulate, however, at different intracellular sites in the in vivo and in vitro situation. The subcellular distribution pattern of 125I-labelled HDL taken up by the cells in vivo is similar to that of the lysosomal marker enzyme acid phosphatase. Peak activity was found at a density of 1.20 g/ml. In vitro 125I-labelled HDL accumulate in an organelle with a medium density of about 1.13 g/ml. This distribution was similar to that of the plasma membrane marker 5' nucleotidase. The subcellular distribution of radioactivity taken up in vivo was changed to lower density by incubating the cells with chloroquine, a drug known to render the lysosomes more boyant. Chloroquine had no effect on the distribution of 125I-labelled HDL taken up by hepatocytes in vitro. PMID- 6251896 TI - Alteration in enzyme activities of de novo phosphatidylcholine biosynthesis in rat liver by treatment with typical inducers of microsomal drug-metabolizing system. AB - 1. The activities of choline kinase, ethanolamine kinase, cholinephosphate cytidylytransferase(s) and cholinephosphotransferase were compared in the liver subcellular fractions after the treatment of rats for two successive days with phenobarbital, 3-methylcholanthrene and polychlorinated biphenyls. 2. The administration of phenobarbital resulted in a significant decrease in choline kinase activity while not affecting ethanolamine kinase activity. Both 3 methylcholanthrene and polychlorinated biphenyls caused considerable enhancement of choline kinase activity concomitantly with ethanolamine kinase activity. 3. The activity of cytosolic cytidylytransferase was not affected by any of the inducers while the microsomal activity was significantly depressed by the administration of either phenobarbital or polychlorinated biphenyls. 4. The activity of microsomal cholinephosphotransferase decreased significantly after the treatment with both 3-methylcholanthrene and polychlorinated biphenyls and increased slightly after phenobarbital administration. 5. The observed opposite effects of phenobarbital and 3-methylcholanthrene on the enzymes in de novo phosphatidylcholine synthesis indicate that there exist a possible relation between induction of microsomal drug-metabolizing system and modulation of phosphatidylcholine biosynthesis in animal liver. PMID- 6251897 TI - Partial purification and properties of mammalian phosphatidylglycerophosphatase. AB - The phosphatidylglycerophosphatase (EC 3.1.3.27) activity of rat liver mitochondria was investigated by assaying the conversion of 14C-labelled phosphatidylglycerophosphate to phosphatidylglycerol. The activity was associated with a mitochondrial membrane fraction and could not be released into solution employing techniques applicable to a peripheral membrane protein. The enzyme was partially purified by sonication, pH 5.0 precipitation, and gel filtration. Various ionic and nonionic detergents as well as numerous divalent cations inhibited the phosphatase. The enzyme displayed a high affinity for phosphatidylglycerophosphate. PMID- 6251898 TI - Solution studies on heme proteins. Circular dichroism and optical rotation of Glycera dibranchiata hemoglobins. AB - Circular dichroism (CD) and optical rotatory dispersion (ORD) spectra of several liganded derivatives of the monomer and polymer hemoglobin components of the marine annelid, Glycera dibranchiata were measured over the wavelength range 650- 195 nm. The differences observed between the monomer and polymer components for the heme dichroic bands in the visible, Soret and ultraviolet wavelength regions seem to result from changes in the heme environment, geometry and coordination state of the central heme iron in these proteins. Within the Soret region, the liganded derivatives of the monomer hemoglobin exhibit predominantly negative circular dichroic bands. The heme band at 260 nm is also absent for the monomer hemoglobin. The ORD and CD spectra in the far-ultraviolet, peptide absorbing region suggest also differences in the alpha-helix content of the monomer and polymer hemoglobins. The values for the single-chain G. dibranchiata hemoglobin are in the expected range (about 70% alpha-helix) as predicted by the X-ray structure of this protein. The lower estimates of the alpha-helix content for the polymer hemoglobin (approx. 50%), may reflect the differences in amino acid composition, primary structure and polypeptide chain foldings. Changes in oxidation state and ligand binding appears to have no pronounced effect on the helicity of either the monomer or polymer hemoglobins. The removal of the heme moiety from the monomer hemoglobin did result in a major decrease in its helix content similar to the loss of heme from myoglobin. PMID- 6251899 TI - Physical-chemical properties of ubiquitin. AB - The secondary structure of ubiquitin, the environment of its single tyrosine residue and its potential for interacting noncovalently with histone 2A or DNA, have been probed by circular dichroism (CD), ultraviolet absorbance, fluorescence and ancillary techniques. The results indicate that ubiquitin has a stable secondary structure containing only a low percentage of alpha-helix or beta sheet. The ubiquitin tyrosine has an elevated pKa arising from the influence of a spatially proximate carboxylate which also causes a marked quenching of the tyrosine fluorescence at neutral pH; the influence of this carboxylate is lost when the protein is unfolded in 7 M guanidine. No evidence has been obtained for the presence of allosteric noncovalent interactions between free ubiquitin and either histone 2A or purified unfractionated DNA. The results suggest that one function of ubiquitin (or of the ubiquitin segment of protein A24) may be to interact with a chromatin component other than histone 2A or DNA, and/or that ubiquitin functions within 2A as a steric blocking group of a region of the nucleosome. PMID- 6251900 TI - Phosphorylation of low molecular weight proteins in purified preparations of rat heart sarcolemma and sarcoplasmic reticulum. AB - A rat heart sarcolemmal preparation could be obtained in which both 5' nucleotidase and adenylate cyclase were enriched approx. 9-fold by subjecting a homogenate to a discontinuous sucrose gradient, without the use of a high salt extraction. After incubation of this fraction with Mg[gamma-32P]ATP, the majority of 32P incorporated was present in 24 000- and 9000-dalton protein components. Only when a heart cytosol fraction or a purified cyclic AMP-dependent protein kinase was added, was enhancement of 32P-incorporaton found by addition of cyclic AMP. The 9000- and 24 000-dalton proteins appeared to be interconvertible. The degree of conversion could be affected by changing the temperature during solubilizaion of the membranes in SDS prior to electrophoresis. This suggested that the 24 000-dalton protein does not correspond to phospholamban, first identified by others in canine heart sarcoplasmic reticulum. Moreover, it could be excluded that the 24 000-dalton protein was derived from contaminating myofibrillar troponin I. When the sarcolemmal fraction was preincubated with Ca2+, Mg2+, ATP and oxalate, contaminating sarcoplasmic reticulum vesicles, loaded with calcium oxalate, settled to a greater density in the sucrose gradient. Membrane constituents other than those with enzymatic activity were monitored to confirm the separation between sarcolemmal and sarcoplasmic reticulum membranes: Coomassie blue staining material, sialic acid, cholesterol and phospholipid. The 24 000- and 9000-dalton proteins were equally distributed among the sarolemmal and sarcoplasmic reticulum fractions present in the sucrose gradient. However, the rate of 32P-incorporation in the presence of heart cytosol fraction was much slowr in the sarcoplasmic reticulum than in the sarcolemmal fraction. PMID- 6251901 TI - The pentaammineruthenium(III)-histidine complex in ribonuclease A as an optical probe of conformational change. AB - The formation of stable transition metal complexes between pentaammineruthenium(III) and the imidazole moiety of histidine residues in ribonuclease A is described. Studies of the kinetics of incorporation suggest that three of the four histidines are reactive and ion-exchange chromatography affords the isolation of three derivatives containing a single ruthenium histidine complex. Equilibrium studies of the thermal- and urea-induced unfolding of one of these derivatives show that the ligand-to-metal change-transfer absorptions above 300 nm can be used to follow the conformational changes in the vicinity of the complex. For the urea-induced unfolding of this derivative, the coincidence of the transition curves obtained from the change-transfer absorptions and from difference ultraviolet spectroscopy at 286 nm, which measures the exposure of buried tyrosine residues to solvent, suggest that only two conformations, native and unfolded, are present at equilibrium in significant concentrations. PMID- 6251902 TI - Relation of the structure and function of ferricytochrome c bound to the phosphoprotein phosvitin. AB - The relationship between the structure and function of ferricytochrome c bound to the phosphoprotein phosvitin was investigated. The rates of reduction of phosvitin-bound ferricytochrome c by cytochrome b2, ascorbate and the superoxide radical generated by xanthine oxidase wer repressed where the binding ratio was less than half the maximum, but at higher ratios they were restored gradually with increase in the ratio. The affinity of cytochrome b2 for cytochrome c was not affected by binding of cytochrome c to phosvitin. The redox potential of the bond form was lower than that of the free form and only decreased with decrease in the ratio. The conformatin around the heme moiety and the electronic structure of the heme group of bound ferricytochrome c were similar to those of free ferricytochrome c, but the conformational stability in the vicinity of the prosthetic group was related to the binding ratio as ratios above half the maximum and was well correlated with the reduction rate. Since the binding of cytochrome c to phosvitin is much stronger at binding ratios below half the maximum, these results suggest that this binding strength exclusively affects the conformational flexibility of the heme crevice in the cytochrome molecule, thus altering the reduction rate. PMID- 6251903 TI - Hormonal regulation of glycogen synthase: insulin decreases protein kinase sensitivity to cyclic AMP. AB - Rat hemidiaphragms incubated with epinephrine exhibited increases in cyclic AMP content and protein kinase activity which were proportional to the logarithm of the hormone concentration from 0.1--2 microM. The fraction of glycogen synthase made independent of glucose-6-P for activity (%I) decreased concomitantly, but correlated only with epinephrine concentrations up to 0.2 microM. Insulin (0--100 mU/ml) increased glycogen synthase %I in a dose-dependent manner with no change in cyclic AMP concentration. Protein kinase activity increased slightly at the lowest insulin concentration, then decreased slightly as glycogen synthase %I increased. Insulin was without effect when administered with a supramaximal dose of epinephrine. In the presence of submaximal epinephrine, insulin produced a dose-dependent increase in glycogen synthase %I which correlated with a decrease in protein kinase activity, without changing cyclic AMP. Insulin had no effect on the increases in cyclic AMP produced by varying levels of epinephrine. However, the activation of protein kinase activity by endogenous cyclic AMP was inhibited in the presence of insulin. The glycogen synthase %I response to epinephrine also was less sensitive in the presence of insulin. Insulin antagonizes the activation of cyclic AMP-dependent protein kinase by epinephrine without altering cyclic AMP levels. PMID- 6251904 TI - Renal parathyroid hormone-dependent adenylate cyclase activity after repletion of vitamin D-deficient rats with vitamin D-2. AB - Rats fed a diet deficient in both vitamin D and Ca2+ exhibited a greater depression of the renal parathyroid hormone (PTH)-dependent adenylate cyclase than was observed in rats fed diets deficient in either vitamin D or calcium. Total serum Ca2+ was decreased from a control level of 11.2 mg/dl to 8.5 mg/dl in rats fed the diet deficient in calcium alone, and to 5.4 mg/dl in rats fed the diet deficient in vitamin D. Serum calcium was decreased further to 4.3 mg/dl in rats fed the diet deficient in both vitamin D and Ca2+. Serum immuno-reactive PTH was significantly elevated over control levels when rats were fed the test diets; however, there were no significant differences between the elevated levels in the three experimental groups. Repletion of rats deficient in vitamin D only with a single oral dose of 3200 I.U. vitamin D-2 resulted in restoration of serum calcium to normal levels, a return of serum PTH to the control state, and an associated increase in PTH-dependent adenylate cyclase activity to the control level by 72 h. Repletion of rats deficient in both vitamin D and Ca2+ with the same dose of vitamin D-2 raised serum Ca2+ to 7.2 mg/dl by 72 h, but did not cause a reduction in circulating PTH, nor did it result in any significant improvement in the responsiveness of the membrane adenylate cyclase to PTH. These results suggest that elevated PTH is a factor in the down regulation of the PTH dependent adenylate cyclase, but do not rule out a role for calcium as a regulatory factor. PMID- 6251905 TI - Specific activation of cyclic AMP-dependent protein kinase(s) by H2-histamine agonists in isolated gastric mucosal cells from guinea-pig. AB - Histamine stimulated cyclic AMP-dependent protein kinase activity in dispersed mucosal cells from guinea-pig gastric fundus (Ka = 5 microM). The H2-agonists dimaprit and impromidine produced similar effects, while the H1-agonist 2-(2 pyridyl) ethylamine had only a weak one. The H2-antagonist cimetidine competitively inhibited 0.1 mM histamine stimulation (Ki = 2 microM). In contrast, the H1-antagonist diphenhydramine had no effect up to 1 mM. PMID- 6251906 TI - Taurine catabolism. II. biochemical and genetic evidence for sulfoacetaldehyde sulfo-lyase involvement. AB - Cell-free extracts of Pseudomonas aeruginosa. TAU-5 catalyze the cleavage of chemically or enzymatically synthesized sulfoacetaldehyde to form acetate and sulfite. The activity is enhanced by the presence of thiamine pyrophosphate. The sulfo-lyase responsible for this reaction has been partially purified 9-fold in order to separate it from taurine: pyruvate aminotransferase and to demonstrate its role in taurine catabolism. The sulfo-lyase is induced in organisms grown on taurine but not on other compounds tested. The induction occurs co-ordinately with the induction of the aminotransferase. Mutagenesis of the organism yielded a strain which lacks the sulfo-lyase and in incapable of growing on taurine. A revertant of this strain regained all the prototrophic characterics. PMID- 6251907 TI - Catecholamine-induced stimulation of adenylate cyclase in parallel with a change in tubulin assembly in Ehrlich ascites tumor cells. AB - In vitro incubation of Ehrlich ascites tumor cells in the presence of norepinephrine induced desensitization of adenylate cyclase to the later norepinephrine stimulation. Such a desensitization was not accompanied by a decrease in the number of receptor sites. Formation of actin filaments from actin monomers was not changed in the desensitized cells, whereas polymerization of tubulin was significantly increased. The increase in the polymerizaton was dependent on the concentration of norepinephrine. PMID- 6251908 TI - Induction of surface glycoprotein expression by cyclic AMP in Chinese hamster ovary cells. AB - Surface expression of a membrane glycoprotein of 135,000 molecular weight (P135) was inducible by adenosine 3',5' -cyclic monophosphate in Chinese hamster ovary cells, CHO-K1 clone. Cells were cultured in the presence or absence of cyclic AMP derivatives, chemicals influencing cytoplasmic cyclic AMP levels, or inhibitors of protein or RNA synthesis. Surface proteins wre radiolabeled by a lactoperoxidase-catalyzed iodination reaction and analyzed by two-dimensional polyacrylamide gel electrophoresis. Surface expression of P135 increased 3---5 fold inthe presence of N6,O2' -dibutyryl cyclic AMP or 8-parachlorophenylthio cyclic AMP. Induction was also observed after treatment with prostaglandins E1 and F2 alpha, but not with sodium butyrate. Phosphodiesterase inhibitor, Roche compound Ro20-1724, enhanced the effect of N6,O2' -dibutyryl cyclic AMP. Metabolic incorporation of [35S]methionine into P135 was increased by N6,O2' dibutyryl cyclic AMP. The induction was sensitive to inhibitors of protein and RNA biosynthesis. These results are consistent with a proposal that cyclic AMP controls the synthesis of this protein. Metabolic incorporation of a radioactive precursor suggested that P135 was a glucos-amine-containing glycoprotein. P135 appeared to be strongly associated with cell membrane because it was resistant to extraction of plasma membrane by cole 0.1 N NaOH. PMID- 6251909 TI - Effect of iodide on estrogen-induced uterine peroxidase. AB - Iodide administered in the drinking water for 5-7 days increased the activity of estradiol-induced uterine peroxidase in the immature rat. This effect was specific for iodide and could not be mimickead by chloride, bromide, thiocyanate, perchlorate or iodate. Sodium iodide also increased peroxidase activity in the parotid gland but had no effect on glucose-6-phosphate dehydrogenase in the uterus, thyroid or parotid even though estradiol produced a 2-fold increase in the activity of this enzyme in the uterus. 125I was taken up more readily by the uterus than by muscle but this process was not influenced by prior treatment of the animals with estrogen. The in vitro effect of sulfhydryl reagents on uterine peroxidase was also investigated and proposals made for possible mechanisms of action of iodide on this enzyme in the intact animal. PMID- 6251910 TI - Activation of cyclic AMP-dependent protein kinase. A common step in vasopressin- and hypertonicity-induced water flow. PMID- 6251911 TI - Properties of a collagenase inhibitor partially purified from cultures of smooth muscle cells. AB - An inhibitor of mammalian collagenase has been partially purified from the spent medium of smooth muscle cells grown in culture. The inhibitor is a glycoprotein with an apparent molecular weight of 25,000. It is stable to heat, acid, and mercurials, but is destroyed by trypsin treatment and by reductive alkylation. The inhibitor interacts with active mammalian collagenase and this interaction results in the loss of enzymatic activity. This presumptive collagenase-inhibitor complex is stable to the treatment with mercurials and to trypsin. These latter observations suggest that this inhibitor is different from other collagenase inhibitors that are thought to be responsible for the latency of the enzyme. PMID- 6251912 TI - Adenosine 3',5'-monophosphate-dependent phosphorylation of a 6000 and a 22,000 dalton protein from cardiac sarcoplasmic reticulum. AB - In canine cardiac sarcoplasmic reticulum, adenosine 3',5'-monophosphate (cyclic AMP)-dependent protein kinase specifically phosphorylates two proteins, as seen by sodium dodecyl sulfate-slab gel electrophoresis and autoradiography. One protein has a molecular weight ranging between 22,000 and 24,000 daltons and has previously been identified and named phospholamban (Tada, M., Kirchberger, M.A. and Katz, A.M. (1975) J. Biol. Chem. 250, 2640-2647). The other protein that the 32P label incorporates into has a molecular weight of approximately 6000. Like the 22,000 dalton protein, the 6000 dalton protein has characteristics of phosphoester bonding. The time-dependent course of phosphorylation shows that initially the 32P label is incorporated more rapidly into the 22,000 dalton protein than the 6000 dalton protein, with both proteins reaching a steady-state level of phosphorylation after 10 min of incubation. When both protein kinase and cyclic AMP are eliminated from the incubation medium, both the 22,000 and the 6000 dalton protein are still phosphorylated, but only to about a quarter of the activity found when cyclic AMP and protein kinases are included in the incubation mixture. The addition of phosphodiesterase completely eliminates the phosphorylation of both proteins. Treating the microsomes with trypsin prevents subsequent phosphorylation of either protein. Phosphorylating the microsomes first, then treating with trypsin, renders both the 22,000 and the 6000 dalton proteins resistant to even prolonged trypsin attack. Unphosphorylated, both proteins are solubilized by a very low concentration of deoxycholate. After phosphorylation the proteins cannot be solubilized by deoxycholate. Phosphorylation appears to alter greatly the physical properties of these proteins. Control experiments exclude the possibility that a lipid is being phosphorylated. After phosphorylation the phosphorylated 22,000 dalton protein is separated from the 6000 dalton protein by proteolipid extraction. After first treating the microsomes with methanol, the 22,000 dalton protein is then soluble in acidified chloroform/methanol, while the 6000 dalton protein remains insoluble. The finding that both proteins have much different biochemical properties when phosphorylated than when not, may be relevant in how they regulate calcium transport in the sarcoplasmic reticulum. PMID- 6251913 TI - Lanthanum stimulates the accumulation of cyclic AMP and inhibits secretion and thromboxane B2 formation in human platelets. AB - La3+ was found to inhibit the secretion of 5-hydroxytryptamine and the production of thromboxane B2 by washed platelets exposed to collagen or thrombin. In addition, La3+ inhibited secretion in response to sodium arachidonate, although the conversion of arachidonate to thromboxane B2 was not affected. La3+ was also found to enhance the accumulation of cyclic AMP under basal conditions and in response to prostaglandin E1, in washed platelets. The inhibition of cyclic AMP accumulation by ADP was prevented by La3+, suggesting that the effect of ADP on cyclic AMP metabolism was dependent upon the presence or flux of calcium at the platelet membrane. La3+ inhibited the activity of adenylate cyclase in platelet lysates both in response to prostaglandin E1 and to F-, indicating a possible effect at the catalytic subunit of the enzyme. None of the observed effects of La3+ could be reversed by the addition of Ca2+ up to 10 mM. The stimulation of cyclic AMP production by La3+ may largely explain the inhibitory effect of La3+ upon platelet secretion and thromboxane B2 production. These results also suggest that Ca2+ localised at the platelet plasma membrane may be important in the regulation of cyclic AMP metabolism. PMID- 6251914 TI - Inhibitory effect of glucose and adenosine 3',5'-monophosphate on the synthesis of inducible N-acetylglucosamine catabolic enzymes in yeast. AB - Glucose can block the utilization of N-acetylglucosamine in Saccharomyces cerevisiae, a facultative aerobe, but not in Candida albicans, an obligatory aerobe. Furthermore, glucose represses the synthesis of the enzymes of the N acetylglucosamine catabolic pathway in S. cerevisiae, but not in C. albicans. The results suggest that catabolite repression is present in S. cerevisiae, but not in C. albicans. Cyclic AMP added to S. cerevisiae cells maintained in a glucose medium cannot bring about their release from catabolite repression. On the contrary, the synthesis of inducible enzymes of N-acetylglucosamine pathway was inhibited by cyclic AMP in both the yeasts. This seems to indicate that cyclic AMP can penetrate into the yeast cells. Furthermore, cyclic AMP inhibits protein synthesis, suggesting that protein synthesis in yeast is under cyclic AMP control. PMID- 6251915 TI - Use of cell fusion techniques to probe the mechanism of catecholamine-induced desensitization of adenylate cyclase in frog erythrocytes. AB - The catecholamine-sensitive adenylate cyclase system appears to be comprised of at least three components; the beta-adrenergic receptor (R component), the catalytic unit of adenylate cyclase (C component) and a nucleotide regulatory protein (N component), responsible for mediating the effects of guanine nucleotides on the system. Cell fusion techniques were used to investigate the role of these three components in the process of homologous desensitization in the frog erythrocyte. Dicyclohexylcarbodiimide (DCCD) was used to inhibit beta receptor function in one population of frog erythrocytes, whilst phenyl glyoxal was employed to inactivate the N and C components in a second population of frog erythrocytes. Using Sendai virus to fuse the two types of modified cell, heterologous beta-adrenergic receptor-adenylate cyclase systems were constructed which contained components from each cell type. When beta receptors from cells previously desensitized to catecholamines were coupled to N-C components derived from fresh erythrocytes, the resulting hybrid exhibited a densitized response to isoproterenol. By contrast, when beta-adrenergic receptors from fresh cells were coupled to N-C components derived from desensitized erythrocytes, no decreased responsiveness to isoproterenol was apparent in the hybrid. That this resensitization was the result of the addition of fresh beta-adrenergic receptors was demonstrated in a control experiment. Frog erythrocytes were desensitized simultaneously to catecholamines and prostaglandin E1 and modified with DCCD which inactivates the beta-adrenergic receptor but not the prostaglandin receptor. When fresh beta-adrenergic receptors were supplied by cell fusion to these doubly desensitized erythrocytes, only the beta-adrenergic response was restored to control levels. The response to prostaglandin remained desensitized in the hybrids, indicating that the observed resensitization of catecholamine stimulated adenylate cyclase activity was specific and was due to the addition of fresh beta-adrenergic receptors. These data suggest that in the frog erythrocyte, homologous desensitization is primarily the result of receptor-related alterations. PMID- 6251916 TI - The role of phosphorylation in the alpha-adrenergic-mediated inhibition of rat hepatic pyruvate kinase. AB - Phenylephrine in the presence of 1-methyl-3-isobutylxanthine and propanolol caused a 40-50% inhibition of pyruvate kinase (type L) activity in isolated hepatocytes, which was accompanied by a 2-3-fold increase in the phosphate content of the enzyme. These changes were blocked by the alpha-adrenergic antagonist dihydroergocryptine and could not be accounted for by the slight increase in cyclic AMP-dependent protein kinase activity generated by the alpha adrenergic agonist. It is concluded that a significant component of the inhibition of hepatic pyruvate kinase mediated by alpha-adrenergic agonists can be attributed to a cyclic AMP-independent alteration in the phosphorylation state of the enzyme. PMID- 6251917 TI - Growth of Penicillium janthinellum on glycine as sole carbon and nitrogen source. AB - Penicillium janthinellum is able to grow on glycine as the sole carbon and nitrogen source. The amino acid is transaminated to glyoxylate which is further metabolised to pyruvate by the glycerate pathway. The reaction product of partially purified glycerate kinase from this fungus is 2-phosphoglycerate. Phosphoglycerate mutase initiates gluconeogenesis from glycine. Partially purified phosphoglycerate mutase is inhibited by fructose 6-phosphate. The possible significance of this regulation is discussed. PMID- 6251918 TI - [Changes in collagen structure under the influence of mechanical dispersion]. AB - Air-dry collagen isolated from cattle retinal layer by means of alkaline-salt treatment was crushed in a laboratory vibro-mill at 80-150 degrees K. Mechanochemical transformations were studied by means of viscosimetry, polarimetry, ESR-spectroscopy and electron microscopy. Mechanical tensions induce breakage of covalent bonds of polypeptide chains, accompanied by a decrease of protein molecular mass, and of lateral interactions, which results in loosening of collagen structure and partial denaturation. PMID- 6251919 TI - [Reaction capacity of the nonequilibrium form of cytochrome c formed during reduction of the protein by radicals]. AB - It has been shown that during fast (< 1 ms) photosensitized by anthraquinone or benzophenone reduction of cytochrome c in 0.15 N NaOH water-glycerol solutions ferrocytochrome c in a nonequilibrium state with increased reactivity was formed. The rate constants for reactions of CO binding to nonequilibrium and equilibrium ferrocytochrome c are 2.10(4) M-1S-1 and 70 M-1S-1 correspondingly. Nonequilibrium cytochrome c is relaxed to corresponding equilibrium state with lambda = 4 S-1. PMID- 6251920 TI - [Effect of the calcium antagonist compound D600 on bradykinin-induced smooth muscle contraction and 14C-D600 binding by a fraction of myometrial cell plasma membranes]. PMID- 6251921 TI - [Model of the selective calcium channel of characean algae]. AB - The present work was intended to further investigate the selective filter of calcium channel on both a cell membrane and reconstructed channels. For the studies on cell membranes, an inhibitor of chloride channels was chosen (ethacrynic acid) to pass currents only through the calcium channels. On both the cells and reconstructed channels, permeability of ions of different crystal radii and valencies was investigated. The obtained results suggest that the channel represents a wide water pore with a diameter larger than 8 A into which ions go together with the nearest water shell. The values of the maximal currents are given by electrostatic interaction of the ions with the anion center of the channel. A phenomenological two-barrier model of the channel is given which describes the movement of all the ions studied. PMID- 6251922 TI - [Electron paramagnetic resonance spectra of iron-sulfur proteins in the mitochondria of bacterial tumors of peas]. PMID- 6251923 TI - [Detection of a paramagnetic product developing during oxidative phosphorylation in mitochondria]. AB - It was shown by ESR technique using flow system combined with ESR-spectrometer that paramagnetic product appearing in the course of oxidative phosphorylation was directly associated with mitochondrial ATPase operation. A decrease of ESR signal intensity and the changes of its form observed on mitochondria uncoupled by 2,4-dinitrophenol as compared with those inhibited by olygomicin suggest that in the case of olygomycin block a free radical ATPase linked intermediate can be recorded, the ESR signal of which seems to be partly due to flavin semiquinone of ATPsynthetase itself. PMID- 6251924 TI - [Principle of parametric ion separation in a molecular model of the sodium pump]. AB - Expressions were obtained for separation coefficients of sodium and potassium ions in macroscopic and molecular models of the sodium pump. Conjugation between the energy-donor process at ATP hydrolysis and ion transport is achieved at the expense of synchroneous changes of the affinity of ion-binding centers and divided cations. i. e. the cyclic changes of energetic profiles in the membrane for each type of ions. The division coefficient in the stationary state is equal to the product of relative changes in selectivity towards the cations of the enzyme ion-binding centers in phosporylated and unphosphorylated states. PMID- 6251925 TI - A model of the complex cell based on recent neurophysiological findings. AB - A neural network model is proposed for the understanding of the receptive field properties of the complex cell. The model is based on recent neurophysiological findings on the visual cortical network. The model is proved to be functionally identical with Hubel's and Wiesel's hierarchy model though the two models are structurally quite different. PMID- 6251926 TI - A layered model for visual processing in avian retina. AB - Visual processing in avian retina is interpreted by means of a layered model in which: a) outer layers provide with spatio temporal fast and retarded versions of the stimuli incident on the retina; a possibility is that horizontal cells are involved in isotropically generating the retarded version which is transversally translated; b) prominent specialization of ganglion cells is the result of local non-linear lateral interaction at the inner plexiform layer, mediated by amacrines which return, also isotropically, the translated retarded signals. Small though systematic deviations in the sites of the lateral interaction result in anisotropic but uniform receptive fields for some ganglion cells. A simple though general expression for the model is derived which includes the various types of recorded avian ganglion retinal cells responses, which also permits a unified interpretation of visual processing in avian and cat's retinae. PMID- 6251927 TI - Lysosomal enzyme activities of human fetal organs during development. AB - The developmental patterns of four lysosomal enzymes have been investigated in liver, kidney, lung, heart, spleen, muscle and brain tissues of human fetuses at varius gestational ages. The largest increment in the activity of all four enzymes, namely acid alpha-glucosidase, alpha-galactosidase, beta-galactosidase and acid phosphatase had been observed in kidney with a 6- to 12-fold increase between the second and third trimester of gestation. The activity of all liver and spleen enzymes also increased considerably during these periods. In muscle, however, only alpha-glucosidase and acid phosphatase showed an increase in the activity, and in lung, acid phosphatase and beta-galactosidase. Most of brain and heart enzymes, except acid phosphatase, did not change significantly during the observation period. The activities of these lysosomal enzymes were also measured in tissues of a normal adult individual, and aspects of the neonatal and postnatal development of these enzymes were discussed. PMID- 6251928 TI - Reduced plasma cyclic AMP level during prophylactic lithium treatment in patients with affective disorders. PMID- 6251930 TI - Differences in cAMP levels in tn- and non-tn-bearing mouse spermatozoa. PMID- 6251929 TI - Cannabis sativa: effects on brain function and ultrastructure in rhesus monkeys. AB - Two studies, designed to control for as many variables as possible, were conducted in 21 rhesus monkeys, some with brain electrodes and some unoperated, to determine the effects of marijuana on brain function and ultrastructure. Some monkeys were exposed to smoke of active marijuana (using different dose schedules), some were administered delta-9-THC (0.69 mg/kg iv), and others were exposed to smoke of inactive marijuana (from which all cannabinols had been removed). To deliver smoke to the monkeys, two different apparatuses were used. Dose schedules comparable to those of human marijuana smokers were established, as determined by plasma levels of delta-9-THC. After 2- to 3-months' exposure, the monkeys that were heavy- and moderate-smokers of active marijuana, and those administered delta-9-THC iv, developed chronic recording changes at deep brain sites, most marked in the septal region, hippocampus, and amygdala. These changes persisted throughout the exposure period (6 or 8 months) and during the postexposure observation period (1 to 8 months). Brains of these electrode implanted monkeys, as well as those without electrodes that were exposed to delta 9-THC, showed ultrastructural alterations characterized by changes at the synapse, destruction of rough endoplasmic reticulum, and development of nuclear inclusion bodies. In contrast, brains of monkeys exposed to smoke of inactive marijuana and of unexposed controls showed no ultrastructural changes. The findings indicate that exposure to delta-9-THC, the psychoactive ingredient of marijuana, at doses commensurate with those used by human marijuana smokers can produce permanent alterations in brain function and structure of monkeys. PMID- 6251931 TI - Oxytocin receptors and parturition in the guinea pig. PMID- 6251932 TI - Calcium and a fucose-sulfate-rich polymer regulate sperm cyclic nucleotide metabolism and the acrosome reaction. PMID- 6251933 TI - Maintenance of receptors for luteinizing hormone by ovine placental lactogen in pseudopregnant rats. PMID- 6251934 TI - In utero evidence for a functional fetoplacental unit in rhesus monkeys. PMID- 6251935 TI - Reversal of follicular fluid inhibition of granulosa cell progesterone secretion by manipulation of intracellular cyclic AMP. PMID- 6251936 TI - Small cell carcinoma of the lung. PMID- 6251937 TI - Pharmacology of airways in the normal and abnormal state. PMID- 6251938 TI - Serologic investigation of herpes simplex virus: usefulness of the double immunodiffusion (DID) technique in epidemiologic surveys. PMID- 6251939 TI - Abdominal wound closure: a trial of Prolene and Dexon. AB - The incidence of wound infection, burst abdomen and incisional herniation after a vertical abdominal incision was studied in a prospective trial comparing polypropylene (Prolene) with polyglycolic acid (Dexon). Wounds were closed by interrupted mass suture with an optional reinforcing continuous closure of the anterior rectus sheath. A total of 347 patients was studied, randomly allocated to suture with either Prolene or Dexon. The two groups were well matched for known risk factors. Dehiscence occurred in 0.6 per cent of patients overall and at 6 months 5.7 per cent of cases had an incisional hernia, although many of these were asymptomatic. There was no difference in the rate of infection, disruption or herniation between the two suture materials. PMID- 6251940 TI - Selective vulnerability of neural cells to viral infections. PMID- 6251941 TI - Clinical and morphological features of gold neuropathy. AB - Three cases of gold-related neuropathy are reported. Clinical features include an acute, symmetrically progressive polyneuropathy, focal or generalized myokymia and a tendency for initial neurological deterioration followed by improvement, after cessation of chrysotherapy. The degree of clinical recovery related to maximal disability. Morphological findings on sural nerve biopsies revealed both axonal degeneration and segmental remyelination. Similar peripheral nerve histology was seen in a parallel animal study in which the severity of the neuropathy was dose-related. PMID- 6251942 TI - Nodal and paranodal membrane structure in complementary freeze-fracture replicas of amphibian peripheral nerves. AB - Complementary freeze-fracture replicas of frog peripheral nerves have revealed new details of membrane structures at the node of Ranvier and paranodal axon Schwann cell junction. At the node both E and P fracture faces of the axolemma have high particle concentrations (approximately 1350/sq. micron and 1600/sq. micron respectively) and these particles do not overlap when tracings from the respective fracture faces are superimposed. A high proportion of the E face particles are large (> 9.5 nm) and cast long shadows while the proportion of large particles in the P face is much lower. In the paranodal region the diagonal pattern of parallel rows in the junctional axolemma always has the same orientation within a given fracture face. In the E face, the parallel rows form a positive (+ 30 degrees) angle to the groove below and in the P face, a negative ( 30 degrees) angle to the ridge above. This implies that the diagonal pattern derives from asymmetric subunits that are able to associate along only one axis and are unable to 'flip over' with respect to the junctional membranes. PMID- 6251943 TI - Maintenance of isolated oligodendrocytes in long-term culture. AB - A new procedure for isolating oligodendrocytes from ovine white matter is described. The method separates oligodendrocytes into two bands on a linear sucrose gradient. Five criteria have been employed to classify the separated cells. It is shown by indirect immunofluorescence with specific antisera that 97% of the cells from both bands carry galactocerebroside, a specific surface marker for oligodendrocytes, on their plasma membranes and 95% of the cells retain myelin basic protein as distinct patches on their surfaces. Isolated cells conform ultrastructurally to current concepts of oligodendrocytes. The cells incorporate [3H]galactose into galactocerebroside and carrier free H2(35)SO4 into sulfatide, specific markers for oligodendrocytes. The specific activity of 2',3' cyclic nucleotide-3'-phosphodiesterase in the two cell fractions is comparable to that reported for isolated oligodendrocytes by others. It is concluded that conservatively, 95% of the cells in both fractions are oligodendrocytes. Cells from both bands survive in culture for months. In vitro the cells extend two or more processes, contain 'gliosomes', and surround themselves with extensive sheet like membranes; i.e. they exhibit the morphological characteristics ascribed to oligodendrocytes in explant cultures. Conservatively 90% of cultured cells stain with an antimyelin basic protein serum. The staining is localized in the cytoplasm and processes. The cells also stain with antigalactocerebroside and antioligodendrocyte sera. Cells remain differentiated for up to 70 days in vitro as evidenced by their incorporation of [3H]galactose and H2(35)SO4 into galactosyl and sulfogalactosylceramide, respectively. PMID- 6251944 TI - Glial fibrillary acidic protein in monolayer cultures of C-6 glioma cells: effect of aging and dibutyryl cyclic AMP. AB - Aging induced a dramatic increase in the number of glial fibrillary acidic protein (GFA) positive cells in monolayer cultures of C-6 cells. Dibutyryl cyclic AMP (DBcAMP) had a similar effect on subconfluent cultures. Both aging and DBcAMP treatment also helped C-6 cells to develop mature astroglia like morphology. PMID- 6251945 TI - Supersensitivity in rat caudate nucleus: effects of 6-hydroxydopamine on the time course of dopamine receptor and cyclic AMP changes. AB - The intranigral administration of 6-hydroxydopamine resulted in the destruction of dopaminergic nerve terminals in the rat caudate nucleus and a 98% decrease in dopamine content. The time courses of the effects of this treatment on dopamine stimulated cyclic 3',5'-AMP accumulation in slices of caudate nucleus and on dopamine receptors in two behaviorally distinct denervation syndromes were determined in an investigation of the mechanisms underlying supersensitivity in this system. The density of dopamine receptors was determined by measuring the high affinity binding of the dopamine receptor antagonist [3H]haloperidol. The density of dopamine receptors was decreased 4 days after the lesion surgery and this effect was probably due to the loss of presynaptic receptors. The density of dopamine receptors and the acumulation of cyclic AMP then increased, with a slower time course, reaching peak levels 10 days after lesioning. The maximal increase in density of dopamine receptors was 70% in both denervation syndromes, while the maximal increase in dopamine-stimulating cyclic 3',5'-AMP levels was 300% at maximally stimulating concentration. The equilibrium dissociation constant (Kd) for haloperidol remained unchanged for 3 weeks following denervation, but there was a slight increase in Kd 40 days post-surgery. The turning behaviour in both syndromes was correlated with a decrease in doapmine levels. The present results are consistent with the notion that the supersensitivity to dopamine that occurs in caudate nucleus following 6 hydroxydopamine lesions has both pre- and post-synaptic components in both syndromes. PMID- 6251946 TI - Relationships between seizure activity and cyclic nucleotide levels in brain. AB - The effects of pentylenetetrazol on behavior, EEG activity and regional CNS levels of cyclic AMP (cAMP) and cyclic GMP (cGMP) in mice and guinea pigs were studied. Pentylenetetrazol increased cGMP levels in all regions of brain examined (cerebral cortex, hippocampus, striatum and cerebellum) and increased cAMP levels in all regions except striatum. cGMP levels were increased by both sub-convulsant and convulsant doses of pentylenetetrazol. In contrast, cAMP levels were elevated only by concentrations of pentylenetetrazol that produced clinically evident seizures or epileptiform EEG activity. These data indicate that increases in CNS cGMP levels produced by epileptogenic stimuli can occur independently of seizure discharges, whereas accumulation of cAMP requires and is secondary to seizure activity. In conjunction with results of other studies, these data support the hypothesis that cGMP may have a role in seizure genesis and/or propagation, whereas cAMP may be involved in processes that attenuate or terminate seizures. PMID- 6251948 TI - Depression of cyclic AMP and cyclic GMP in the cerebrospinal fluid of rats after acute administration of ethanol. AB - The effect of single oral doses of ethanol on the levels of cyclic AMP and cyclic GMP in the cerebrospinal fluid was studied in rats. Ethanol markedly decreased the levels of both cyclic nucleotides for at least 24 h. The decrease of cyclic nucleotides after medium and high doses (1.65 and 4.59 g/kg) was slower in onset but more pronounced than the decrease after a low dose (0.55 g/kg) of ethanol. PMID- 6251947 TI - Glial-released proteins in clonal cultures and their modulation by hydrocortisone. AB - Rat glial C6 cells release into the culture medium a reproducible spectrum of soluble proteins of 12 major peaks over a broad molecular weight range as determined by fractionation on SDS-gel electrophoresis. Exposing C6 monolayers to hydrocortisone (HC) results in a selective alteration in the pattern of glial released protein (GRP). The selective HC-induced increase or decrease in GRP peaks is specific to HC in that 17 beta-estradiol, dibutyryl cyclic AMP, isoproterenol and melatonin exert either no detectable or a qualitatively different influence on the GRP pattern. The HC influence is dose dependent over a physiological range of concentrations from 10(-9) to 10(-6) M. Differences in culture age and in subclones of C6 can influence both the normal and the HC induced pattern of GRP. The origin of th GRP is unknown, but pattern reproducibility, viability tests, surface labeling studies and metabolic labeling studies of soluble and particulate compartment proteins and glycoproteins support the position that cell lysis is not an important source of GRP. More importantly, these studies indicate that GRP and HC-induced changes in GRP pattern are physiologically significant aspects of glial cell behavior. PMID- 6251949 TI - A study of the quantal (all-or-none) change in reflex latency produced by opiate analgesics. AB - The properties of opiate-induced changes of tail-flick latency were studied in the rat. (1) Morphine and pentazocine produced a stepwise increase in latency which rose from near baseline to cut-off (usually greater than 20 sec) in less than 30 sec. Abrupt return to pre-treatment latencies was observed either spontaneously or when the rat was back-titrated with the narcotic antagonist naloxone. (2) The proportion of rats showing this stepwise change increased with increasing dose; however, the step itself was independent of dose. The same step was produced by a slow, constant infusion of morphine but was not produced by ice water stress or barbiturate administration. (3) Increasing heat intensity to the tail shortened the baseline latency and raised the mean dose of morphine required to produce a step latency increase. (4) A step increase in latency was also observed when paw withdrawal instead of tail-flick was measured. We hypothesize that the analgesic behavior described partly defines the operating characteristics of an intrinsic endorphin-mediated analgesia system which mediates narcotic suppression of withdrawal reflexes. PMID- 6251950 TI - The response of rabbit ciliary nerve to luminance intensity. AB - Using cervical sympathectomized and immobilized rabbits, the relationship between the luminance intensity and the magnitude of the response in pupillo-constrictor units of the ciliary nerve was investigated. It was revealed that the intensity- response relationship of the units closely resembled that of retinal receptors. Therefore, it would seem that retinal information concerning luminance is relayed without alteratin to the ciliary nerve in spite of passing through a number of synapses. PMID- 6251951 TI - Effects of focal electrical stimulation and morphine microinjection in the periaqueductal gray of the rat mesencephalon on neuronal activity in the medullary reticular formation. AB - Neurons in the medullary reticular formation (MRF; nucleus reticularis gigantocellularis and nucleus reticularis paragigantocellularis) were evaluated for their involvement in the analgesia produced by focal electrical stimulation and microinjection of morphine into the periaqueductal gray region (PAG) of the rat mesencephalon. Analgesia-producing PAG stimulation altered the spontaneous activity of 80% of the neurons in the MRF (both excitation and inhibition were observed) and inhibited the noxious-evoked excitation of 75% of MRF neurons. Microinjection of morphine into the PAG also increased (50%) and decreased (17%) the spontaneous activity of MRF units and inhibited the noxious-evoked excitation of 47% of MRF neurons. These effects were specific for analgesia produced by the PAG manipulations and were partially reversed by naloxone. The role of the MRF in PAG-induced analgesias and the degree of overlap in neuronal systems influenced by intracranial morphine and electrical stimulation is discussed. PMID- 6251952 TI - Decreased beta-adrenergic responses in the female rat brain are eliminated by ovariectomy: correlation of [3H]dihydroalprenolol binding and catecholamine stimulated cyclic AMP levels. PMID- 6251953 TI - The shift-effect enhances X- and suppresses Y-type response characteristics of cat retinal ganglion cells. AB - Responses to a number of stimuli have been studied during the continuous movement of a "global" pattern covering a large part of the retina but excluding the receptive field of the ganglion cell under investigation. With remarkable consistency, the motion of the pattern induced a reinforcement of response properties usually associated with X-cells. In particular, the following responses characteristic of Y-cells were abolished or strongly reduced: (1) the response to simultaneous increment and decrement switching in a bipartite field in the receptive field center; (2) the "discrete" shift-effect, elicited by a jerk of the global pattern; and (3) the relative elevation of the mean discharge rate as a response to a fine drifting grating. Futhermore, responses to center illumination became sustained, and the ongoing discharge rose ("continuous shift effect"). Y-type responses were most strongly affected, except for the sustained components of center responses which increased in a rather unpredictable way. The results strengthen the view that the shift-effect accounts for most of the functional differences between X- and Y-cells. Saturating the shift-effect mechanism by continuous stimulation is a tool by which the shift-effect components in Y-type responses can be largely removed so that essentially X-type responses are left. Possible neuronal pathways involved in the transmission of the resposes are discussed. PMID- 6251954 TI - Reversible inactivation of raphe magnus neurons: effects on nociceptive threshold and morphine-induced analgesia. PMID- 6251955 TI - Human nociceptive reactions: effects of spatial summation of afferent input from relatively large diameter fibers. PMID- 6251956 TI - Serotonin, dopamine and intracellular cyclic AMP inhibit the responses of nicotinic cholinergic membrane in snail neurons. PMID- 6251957 TI - Canadian contributions towards the comprehension of hyperinsulinism: the first successful excision of an insulinoma. AB - The authors review briefly the contributions to the "insulin story" made by Canadian doctors. A.G. Nichols from the department of pathology, McGill University, first described an adenoma arising from the islets of Langerhans. The authors also review the background to the first successful excision of a functioning tumour of the pancreas by R.R. Graham in 1929; in the preceding 2 years W. J. Mayo had found a malignant islet cell tumour with hepatic metastases and J.M.T. Finney had operated on a patient suffering from functional hypoglycemia. Graham found and successfully excised what was probably a solitary benign islet cell adenoma. The authors believe the patient was cured. PMID- 6251958 TI - Familial pseudohypoparathyroidism without somatic anomalies. AB - A family is described in which affected individuals showed pseudohypoparathyroidism, with hypocalcemia, hyperphosphatemia and increased serum levels of parathyroid hormone, but none of the somatic anomalies frequently associated with this disorder. The untreated individuals showed radiologic evidence of osteitis fibrosa. The administration of parathyroid hormone evoked only a slight increase in the excretion of cyclic adenosine monophosphate but no change in the renal tubular reabsorption of phosphate and no rise in the serum calcium level. The infusion of ethylenediamine tetra-acetic acid caused an appropriate increase in the serum level of parathyroid hormone, but again there was no apparent renal or skeletal response to the hormone. There were no associated abnormalities in calcitonin, thyrotropin or prolactin levels and no thyroid dysfunction. Therapy with vitamin D corrected the hypocalcemia but did not improve the renal and skeletal responsiveness to parathyroid hormone. The inheritance of the disorder in this family was compatible with an autosomal dominant mode with variable penetrance, but other modes could not be excluded. PMID- 6251959 TI - 67Ga scintigraphy in granulocytic sarcoma. AB - Several granulocytic sarcomas (chloromas) developed in a patient with acute myelogenous leukemia while in hematologic remission. A positive diagnosis of the symptomatic lesion was made by means of open biopsy examination. The other lesions, which were unsuspected, were detected with a 67Ga-citrate scan. Subsequent 67Ga-citrate scans indicated a favorable response to treatment. The incidence and significance of silent granulocytic sarcomas in patients in hematologic remission is not known. Documentation of such lesions might prove valuable for diagnosing extramedullary relapse or for delivering intensive local therapy. PMID- 6251960 TI - Fanconi anemia. Oxymetholone hepatic tumors, and chromosome aberrations associated with leukemic transition. AB - Jaundice and hepatomegaly developed in a boy with Fanconi anemia after he had undergone treatment with oxymetholone for nine years. A liver scan showed patchy uptake consistent with the presence of space-occupying lesions. After oxymetholone treatment was stopped, the jaundice resolved, the liver size decreased, and the filling defects were no longer detectable on the liver scan. A year later, 5% of his white blood cells showed a consistent chromosomal abnormality. His leukocyte count increased and 85% of these cells showed the same chromosomal abnormality. The rapid replication of this abnormal clone suggests that it was leukemic. The significance of oxymetholone therapy and the occurrence of hepatic tumors and leukemia is discussed. PMID- 6251961 TI - Hepatocellular carcinoma. Polygonal cell type with fibrous stroma--an atypical variant with a favorable prognosis. AB - Hepatocellular carcinoma, even when treated with operative resection, is generally regarded as uniformly fatal. Isolated reports of an unusual histologic variant characterized by polyglonal cells with a fibrous stroma (PCFS) suggest a more favorable outcome. Twelve cases of PCFS, representing the largest reported group, are presented. The mean age of the patients at the time of onset was 23.1 years and the male to female ratio was 1:2. Successful operative resection of the primary neoplasm and metastatic foci has resulted in a significant percentage of long-term survivors with a mean survival time of 68 months and two- and five-year survival rates of 82% and 63%, respectively. The variant shows cytologic similarity to differentiated hepatocellular carcinoma with a unique stromal appearance suggesting a pattern of fibrosis associated with focal nodular hyperplasia. Focal nodular hyperplasia is noted occasionally in the liver adjacent to PCFS. The possibility that PCFS represents an intermediate stage between focal nodular hyperplasia and the more malignant variants of hepatocellular carcinoma is discussed. PMID- 6251962 TI - Effect of antineoplastic drugs on human leukocyte-mediated cytotoxicity against herpes simplex virus infected cells. AB - We evaluated the effect of five antineoplastic drugs on the ability of human leukocytes to destroy herpes simplex virus (HSV) infected target cells in the presence of antibody (antibody-dependent cellular cytotoxicity) and in its absence (natural killer cytotoxicity). Leukocytes from healthy volunteers were separated into macrophages, polymorphonuclear leukocytes, and lymphocytes. Adriamycin, cyclophosphamide, prednisone, procarbazine, and vincristine, at various concentrations and incubation periods, were tested for their effects on the natural killer and antibody dependent cellular cytotoxicity of macrophages, lymphocytes, and polymorphonuclear lymphocytes in a 51Cr release microcytotoxicity assay against HSV-infected cells. All drugs at therapeutic concentrations inhibited natural killer and antibody dependent cellular cytotoxicity; an exception was cyclophosphamide, which did not inhibit the natural killer cytoxicity of lymphocytes. The antibody dependent cellular cytotoxicity of macrophages and polymorphonuclear leukocytes appeared to be more than that of lymphocytes. The results of short incubation (2 hours) of the drug with either effector cells or target cells, followed by drug removal, suggests that the drug effect occurred early and predominantly at the effector cell level. Antineoplastic drugs had an inhibitory effect on natural killer and antibody dependent cellular cytotoxicity against HSV-infected cells. This inhibitory action may partially explain the increased susceptibility of patients receiving chemotherapy to developing viral infections. PMID- 6251963 TI - Purification of herpes simplex virus tumor associated antigen from human kidney carcinoma. AB - In the present study, we attempted to purify herpes simplex virus (HSV) tumor associated antigen(s) (TAA) extracted from human kidney carcinoma. Trypsinized human tumor cells were sonicated for 9 minutes and clarified at 100,000 x g for 1 hour; the supernate yielded 70% of detectable TAA as determined by means of quantitative absorption with specific antisera. The supernate used as source of soluble HSV-TAA was concentrated and the pellet was resuspended in 0.02 M tris, pH 7.2, and purified by means of filtration on Sephadex G-100 followed by chromatography on DEAE Sephadex A-50 and then affinity chromatography on concanavalin A (Con A) sepharose. The TAA bound to Con A sepharose was eluted by 0.5 M of alpha-CH3D-mannoside (alpha-MM) and behaved as a glycoprotein. The molecular weight determined on SDS-PAGE was about 70,000 daltons in relation to standard marker proteins. This antigen reacted in complement fixing tests with hyperimmune guinea pig sera as well as with certain human squamous cancer sera. As a control we used a human kidney carcinoma which showed no complement fixing activity in any of the procedural steps, and as control sera, guinea pig sera prepared by inoculation of uninfected guinea pig cells. PMID- 6251964 TI - Hemorrhagic infarcts caused by mucin emboli mimicking brain purpura. AB - The macroscopic aspect of brain purpura was mimicked by multiple hemorrhagic infarcts arising in the vascular supply region of small arteries occluded by embolized mucin in a case of scar adenocarcinoma of the right lower pulmonary lobe, which had extensively permeated pulmonary blood vessels. The pathophysiology is discussed along with its clinical implications. PMID- 6251965 TI - Hepatitis B surface antigen and hepatocellular carcinoma in the People's Republic of China. AB - Eighteen cases of heptocellular carcinoma from the People's Republic of China were investigated for the presence of hepatitis B surface antigen (HBsAg) in the cytoplasm of hepatocytes and tumor cells. The Sternberger-PAP immunoperoxidase technique utilizing monospecific antibody to HBsAg and a modified orcein method demonstrated cytoplasmic HBsAg in hepatocytes of 15 cases (83.3%) and tumor cells of 3 cases (16.7%). Thirteen of these cases were also investigated for HBs antigenemia and of these 11 were positive (84.6%). These hepatomas were often associated with macronodular cirrhosis and/or a persistent inflammatory process in the hepatic parenchyma. The high association of HBsAg and hepatoma indicates that the hepatitis B virus plays an important role in the pathogenesis of this malignancy in China. It is concluded that a major public health effort to eradicate endemic hepatitis B infection is the most reasonable way to decrease the incidence of this cancer, which is common in China. PMID- 6251966 TI - Management of adenoid cystic carcinoma of the uterine cervix (cylindroma): report of six cases and reappraisal of all cases reported in the medical literature. AB - We report 6 new cases of adenoid cystic carcinoma (cylindroma) of the uterine cervix (5, invasive cancer and 1, in situ cancer). All 6 patients were elderly women and 5 were hypertensive. Additionally, 3 (Patients 1, 2, and 4) were obese and 1 (Patient 3) had diabetes mellitus. Three patients were seen because of postmenopausal vaginal bleeding and 3 were found to have malignant cells on routine exfoliative cytologic examination. Histologically, the tumor cells were relatively uniform, with scanty cytoplasms and a palisading pattern at the periphery of the tumor masses. Round cystic spaces were found in all 6 cases and hyaline nodules were present in some of the cyclic spaces in 2. The tumors were found in Stages IA, IB, IIB, IIB, and IIIB (cases 1-4 and 6 respectively), and were treated with irradiation only. There have been only 38 cases of invasive adenoid cystic carcinoma of the cervix reported in the world medical literature. We review the treatment and survival for all 38 cases previously reported and add 5 new cases. PMID- 6251967 TI - Effect of dibutyryl cyclic adenosine 3'5'-monophosphate on mitotic activity in the thyroid of hypophysectomized rats. AB - Effect of dibutyryl cyclic adenosine 3'5'-monophosphate (dbcAMP) on mitotic activity in the thyroid of hypophysectomized rats has been examined. It has been demonstrated that dbcAMP stimulates the incidence of mitoses in the thyroid follicular cells. It is therefore suggested that cAMP may be a mediator of the proliferogenic effect of TSH on the thyroid in vivo. Cyclic AMP could also release some unidentified growth-promoting factors for the thyroid. A direct stimulating effect of dbcAMP on the proliferation of the thyroid follicular cells is assumed to be possible as well. PMID- 6251968 TI - Structural and microspectrofluorometric studies on glial cells from the periventricular and arcuate nuclei of the rat hypothalamus. AB - Fluorescence spectroscopy and electron microscopic techniques have been employed to investigate a class of glial cells that is characterized by the presence in their cytoplasm of large fluorescing inclusions that stain with paraldehyde fuchsin or chrome-hematoxyline-alum. In the periventricular nucleus the cells have been identified as a population of astrocytes whose inclusions emit an orange-red fluorescence. In the arcuate nucleus there are, in addition to an overwhelming majority of such astrocytes, also some microglial cells with similar characteristics. The ability of the latter to emit any kind of fluorescence has not yet been established. The fluorescence maximum of these astrocytic inclusions was found to be at 640 nm when excited at 405 nm. The data obtained suggest that the fluorescence observed is due to the presence of porphyrins in the astrocytic inclusions. In the majority of our electron microscopic pictures the inclusions lack a bounding membrane. By contrast, neuronal lipofuscin has an outer membrane. In cryostat sections, the lipofuscin emits a yellow fluorescence when excited at 400-410 nm. PMID- 6251969 TI - Transposable elements. PMID- 6251970 TI - Eucaryotic transposable genetic elements with inverted terminal repeats. AB - DNA carrying inverted repeats was tested for transposition within the Drosophila genome. Five Bam HI segments containing related inverted repeats were isolated from D. melanogaster and analyzed by electron microscopy and restriction mapping. Southern blot experiments using single-copy flanking sequences as probes allowed the study of DNA arrangements at specific sites in the genomes of five closely related strains. We found that in some genomes the sequences with inverted repeats were present at a particular site, whereas in other genomes they were absent from this site. These results indicated that three of the sequences are transposable genetic elements. In one case we have purified the two corresponding DNA segments, with and without the sequence containing inverted repeats, thereby confirming the mobility of this sequence. These DNA elements were found to be distinct in two ways from copia and others previously described: first, they contain inverted terminal repeats, and second, they have a more heterogeneous construction. PMID- 6251971 TI - An E. coli gene product required for lambda site-specific recombination. AB - We report characteristics of himA mutations of E. coli, selected for their inability to support the site-specific recombination reaction involved in the formation of lysogens by bacteriophage lambda. The himA allele lies at minute 38 on the chromosome. Three noncomplementing and closely linked mutations define the himA locus; one is a nonsense mutation which shows that the gene product is a protein. HimA mutations reduce both lambda integrative and excisive site-specific recombination. Since dominance tests demonstrate that himA mutations are recessive, it is probable that the himA protein is either a necessary component for site-specific recombination or, alternatively, regulates the expression of such a function. HimA mutations exhibit pleiotropic effects. They reduce integration of phages that have different attachment specificities from lambda and inhibit the growth of phage mu. In addition, himA mutations reduce precise excision of integrated phage mu as well as Tn elements. This pleiotropy suggests that the role of himA protein is nonspecific. Since all of the processes affected by himA mutations ultimately rely on protein-DNA interactions, we suggest that himA protein may act in an auxillary manner to facilitate these interactions. PMID- 6251972 TI - Viral infection permeabilizes mammalian cells to protein toxins. PMID- 6251973 TI - Structure and gene organization in the transformed Hind III-G fragment of Ad12. AB - The nucleotide sequence of the transforming Hind III-G fragment of Ad12 DNA which encompasses the left 6.8% of the genome has been determined. The fragment was 2320 nucleotides long, and contained a GC cluster at positions 126-155 and a region extremely rich in AT at positions 1098-1142 (number from the leftmost end). Possible coding regions for the two transforming gene products were assigned. The predicted coding region for T antigen g is positions 502-1069 and positions 1144-1373, which are joined by splicing (266 amino acid residues, 30 kd), and that for T antigen f is positions 1845-2126 (94 amino acid residues, 10 kd). The sequence of the Hind III-G fragment was compared with that of the transforming DNA fragment of Ad5 which encompasses the left 8.0% of the genome (2809 nucleotides). There are several discrete regions with significant sequence homology. The comparison suggests that the regions in the left two thirds of the Ad5 and Ad12 transforming DNA fragments (map units 0-4.7% in Ad5 and 0-4.4% in Ad12) bear some resemblance in their gene organizations, and code for proteins containing structurally homologous regions. PMID- 6251974 TI - Evidence that the phosphorylation of tyrosine is essential for cellular transformation by Rous sarcoma virus. PMID- 6251975 TI - LDL receptors in coated vesicles isolated from bovine adrenal cortex: binding sites unmasked by detergent treatment. AB - Coated vesicles isolated from bovine adrenal cortex contain specific binding sites that recognize 125I-labeled human low density lipoprotein (LDL). These sites share the properties of the functional LDL receptors previously demonstrated on the surface of adrenal cells and in unfractionated adrenal membranes. Approximately 90% of the LDL receptors of the isolated coated vesicles were initially masked. Binding of 125I-LDL increased 10 fold after the vesicles were disrupted with the detergent octylglucoside. The LDL receptors of intact coated vesicles were also shielded from destruction by pronase; proteolytic destruction occurred only after the vesicles had been disrupted with octylglucoside. The adrenal coated vesicles measured 60 nm in diameter, suggesting that they were derived from the Golgi apparatus. Like the previously studied coated vesicles from brain and other tissues, the coated vesicles from adrenal cortex contained clathrin as the major protein component. In contrast to the coated vesicles of adrenal cortex, however, the brain coated vesicles failed to reveal masked LDL receptor activity when treated with octylglucoside. The current data indicate that isolated coated vesicles from the adrenal cortex contain LDL receptors and that these receptors exist in a masked form, apparently because their binding sites face the interior of the vesicle. PMID- 6251976 TI - Serum factors required for arginase induction in macrophages. PMID- 6251977 TI - Lymphokines secreted from sodium periodate-treated lymphocytes. PMID- 6251978 TI - Morphological reverse transformation of Chinese hamster ovary (CHO) cells and surface fibronectin. AB - Alterations in the distribution of surface fibronectin during reverse transformation of chinese hamster ovary (CHO) cells induced by dibutyryl adenosine cyclic monophosphate (dbcAMP) and theophylline was examined by indirect immunofluorescence. dbcAMP-induced reverse transformation was not followed by any significant increase in surface fibronectin up to 48 hrs after treatment. Reverse transformation induced by theophylliner by itself or in combination with dbcAMP is followed several hours later by a phenomenal increase in fibrillar surface fibronectin, which is largely persistent even in the presence of cytochalasin-B or colcemid but is sensitive to the presence of cycloheximide. It appears that reverse transformation consists at least of two steps: (a) morphological reversion to normal phenotype and (b) modulation of cell membrane properties or components favouring retention of fibronectin in the cell surface. PMID- 6251979 TI - Dissociation of uridine and (86Rb+) uptake from stimulatioin of DNA synthesis in Swiss 3T3 cells. AB - The importance of the stimulation of uridine and (86Rb+) uptake to the stimulation of DNA synthesis was investigated using three defined growth factors, EGF, FGF, and PGF2 alpha, and three hormones, hydrocortisone, insulin and PGE1, which do not stimulate proliferation of Swiss 3T3 cells but modify the response to these growth factors. Uridine uptake is stimulated by insulin, but not by PGF2 alpha, indicating that its activation is neither sufficient nor necessary for stimulation of cell proliferation. (86Rb+) uptake was stimulated by each growth factor tested, but also by insulin and PGE1. Modifying effects of insulin, hydrocortisone or PGE1 in combination with growth factors on the level of DNA synthesis were not reflected in changes in stimulation of these uptake systems. We conclude that these events are regulated separately and are not tightly coupled to the initiation of DNA synthesis. PMID- 6251980 TI - [Recurrent keratoconjunctivitis epidemic caused by adenovirus type 29 in the North Bohemia region]. PMID- 6251981 TI - [Herpesviruses, especially Epstein-Barr virus, in the child's environment]. PMID- 6251982 TI - Routine enterovirus diagnosis in a human rhabdomyosarcoma cell line. AB - For many years a substitute cell line has been sought to replace monkey kidney cell cultures for the diagnosis of enterovirus infections. Reports by various workers have shown that the RD cell line, derived from a human rhabdomyosarcoma, will support the replication of most of the prototype strains of enterovirus. The present study shows that, with the exception of the group B coxsackieviruses, RD cells are more sensitive than cynomolgus monkey kidney cultures for the isolation of a wide variety of enteroviruses from clinical specimens. Since regular access by many diagnostic laboratories to supplies of primary cell cultures is often difficult because of distance from source or cost factors, a simple cell culture system is proposed which should prove useful for the diagnosis of most of the important enterovirus infections. PMID- 6251983 TI - Two receptor forms for ouabain in sarcolemma-enriched preparations from canine ventricle. AB - Some evidence indicates that the inotropic effect of cardiac glycosides occurs at concentrations too low to affect Na+,K+-ATPase activity. This suggests that some receptor other than Na+,K+-ATPase mediates the inotropic effect. We studied ouabain binding to sarcolemma-enriched preparations from canine ventricle under conditions known to promote binding to Na+,K+-ATPase. Profiles for binding and dissociation were characterized by two kinetic components: (1) fast association and slow dissociation; (2) slow association and fast dissociation. Profiles in the absence of supporting ligands were consistent with a single species of receptors with slow association, fast dissociation and minimal effect on Na+,K+ ATPase activity. Binding supported by magnesium plus inorganic phosphate inhibited Na+,K+-ATPase activity by 86%. The two binding components were affected differentially by heating at 55 degrees C. It was concluded that the preparation possesses two receptors for ouabain: the Na+,K+-ATPase and a "new" receptor. The latter may be different chemically from the Na+,K+-ATPase. The more likely possibility is that the "new" receptor is the Na+,K+-ATPase in a state characterized by low catalytic activity, low affinity for ouabain, and no requirement of specific ligands for ouabain binding. Further, the data suggest an interdependence between the two forms. This leads to a mechanism which allows an inotropic effect to precede loss of Na+,K+-ATPase activity even though both result from glycoside binding to Na+,K+-ATPase. The mechanism involves an equilibrium between inactive and active forms of the Na+,K+-ATPase such that the inactive form buffers loss of the active form upon exposure to a cardiac glycoside. PMID- 6251984 TI - Advantage of Florisil over charcoal separation in a mechanized testosterone radioimmunoassay. AB - We have facilitated radiommunoassay of testosterone by mechanizing every pipetting step and separating bound from free hormone by shaking assay tubes with activated magnesium silicate (Florisil) in a multi-tube Vortex mixer. Compared with dextran-charcoal separation, Florisil separation has the advantage that testosterone is only negligibly adsorbed except during active shaking, so that the interval for adding adsorbent does not produce discrepancies in bound hormone estimates between first and last assay tubes in a series. Our method gave CVs of 5% (within assay) and 6% (between assay) for samples containing 4.0 mug of testosterone per liter, considerably better than those obtained with charcoal (respectively 12 and 15%). The assay also had low blank values and demonstrated excellent accuracy. PMID- 6251985 TI - Serum glutathione S-transferase activity in liver diseases. AB - Assay conditions of human liver glutathione S-transferase and its activity in human serum from liver disease patients were investigated. One mmol/l reduced glutathione, and 1 mmol/l-1-chloro-2,4-dinitrobenzene, pH 6.5, were used for the measurement, because of the very low non-enzymatic conjugation. Glutathione S transferase activity was inhibited by bilirubin, but this inhibition was counteracted by the presence of a low concentration of albumin. The normal human serum glutathione S-transferase activity was 5.2 +/- 2.4 I.U./l (mean +/- S.D.), and was not influenced by any differences of age, sex or leukocyte count. A significant increase in serum enzyme activity was noted in cases of acute hepatitis with GPT exceeding 200 I.U./l, primary hepatoma and metastatic liver cancer. Some of the cases with fulminant hepatitis showed extremely high values. The degree of correlation between serum glutathione S-transferase and GOT or GPT was high in acute hepatitis, with GOT or GPT exceeding 200 I.U./l, in fulminant hepatitis, primary hepatoma and gall stones, while in chronic hepatitis and liver cirrhosis it was low. In cases of acute hepatitis and fulminant hepatitis, the disappearance of serum glutathione S-transferase from the blood was much faster than that of GOT and GPT. Serum glutathione S-transferase measurements will provide new and unique information for the diagnosis of acute liver diseases. PMID- 6251986 TI - Sphingomyelinase activities of various human tissues in control subjects and in Niemann-Pick disease - development and evaluation of a microprocedure. AB - A micromethod was elaborated for the assay of sphingomyelinase activities with native labelled substrate in leukocytes, cultivated skin fibroblasts, liver tissue and cultivated amniotic fluid cells. The optimal assay conditions and specific activities in control samples were investigated for each enzyme souce. No significant difference was found between results obtained either with the micromethod or with our previous procedure. Findings obtained in pathological material from 62 patients with the various forms of Niemann-Pick disease and 21 obligate heterozygotes by one or another method are reported. A generalized severe sphingomyelinase deficiency was observed in all cases with Niemann-Pick disease type A or B, while in Niemann-Pick disease type C, sphingomyelinase activities were normal in leukocytes, elevated in liver tissue and partially deficient in cultivated skin fibroblasts. Six pregnancies at risk were monitored. PMID- 6251987 TI - "Tryptic-like" activity in sera of patients with pancreatitis. AB - Serum trypsin esterolytic activity was measured in 106 sera from 61 controls and 45 patients with pancreatitis. A trypsin specific synthetic substrate, N-alpha benzoyl-L-arginine-paranitroanilide, was used. High levels of enzymatically active trypsin were shown to be present in serum of patients with pancreatitis. No difference between the two samples was noticed for the serum concentrations of alpha-1-antitrypsin and alpha-2-macroglobulin (the two main serum trypsin inhibitors). Active trypsin was contained in the high molecular weight fraction of plasma proteins, corresponding to a complex with alpha-2-macroglobulin. The determination of serum typsin activity as a sensitive test for detection of pancreatitis was demonstrated to be statistically significant. PMID- 6251988 TI - Familial occurrence of trophoblastic disease - report of recurrent molar pregnancies in sisters in three families. AB - Three families are described in which trophoblastic desease occurred in one or more pregnancies in two or more sisters. The possible role of genetic factors in the etiopathogenesis of hydatidiform mole is reviewed in light of these data. We believe this to be the first report of familial occurrence of molar pregnancies. PMID- 6251989 TI - Thyroid-stimulating antibody (TSab) detected in sera of Graves' patients using human thyroid cell cultures. PMID- 6251990 TI - A review of small cell lung cancer: diagnosis and treatment. PMID- 6251991 TI - [Recurrent adenoma of the islands of Langerhans. A case]. PMID- 6251992 TI - [Scanner examination of mediastinal neurogenic tumours. Twelve confirmed cases (author's transl)]. PMID- 6251993 TI - Free radical initiation in proteins and amino acids by ionizing and ultraviolet radiations and lipid oxidation--Part I: ionizing radiation. AB - Parallels and similarities in chemical and functional damage to proteins by ionizing and UV radiations and oxidizing lipids have been recognized for some time. However, only recently have oxidizing lipids been shown directly by electron spin resonance to be radiomimetic also in their capacity for protein free radical production. Free radicals play a key role in the transformation of energy to molecular and cellular damage. It is thus of critical importance to elucidate the general mechanisms of free radical formation and reactions in proteins in order to understand protein involvement in various pathological conditions and in food deterioration. Accordingly, this review is a detailed comparison of gamma radiation, UV radiation, and lipid oxidation for what is presently known concerning (1) the specific modes of energy deposition and free radical formation, (2) the free radicals formed in proteins and amino acids, and (3) the typical damage correlating with these radicals. PMID- 6251994 TI - Granular cell tumor. AB - The case report presented herein involves a granular cell tumor of the vulva, an uncommon site, with unusual clinical characteristics. PMID- 6251995 TI - Toxic effects of ethambutol. PMID- 6251996 TI - Persistent lymphocytopenia as a diagnostic feature of bronchogenic carcinoma. AB - Patients with abnormalities due to bronchogenic carcinoma, noted on chest films, have decreased peripheral blood lymphocytes and increased total white cells compared to patients with benign lesions. Precision studies of 40 patients revealed that a low percentage of lymphocytes averaged over a three-week period distinguished bronchogenic carcinoma patients from patients with benign lesions with 95 percent overall accuracy. Lesions as small as 1.0 cm were correctly predicted to be malignant. Mean 8 AM plasma cortisol levels were elevated in patients with bronchogenic carcinoma and there was a negative correlation of 8 AM plasma cortisol levels with precentage of lymphocytes. Increased levels of endogenous cortisol may account for lymphocytopenia in bronchogenic carcinoma patients. PMID- 6251997 TI - Clostridial pleuropulmonary infection. AB - Primary clostridial pleuropulmonary infection occurred in two patients. The pathogenesis of infection was related to aspiration of oropharyngeal contents or hematogenous seeding of infarcted lung tissue. One patient was cured with penicillin; the other died secondary to sepsis and respiratory failure. Review of 13 additional cases from the literature demonstrated pulmonary infection due to Clostridia to be characterized by lobar or multilobar disease with uniform involvement of the pleura. Iatrogenic contamination of the pleural space may play some role in the pathogenesis of infection. The treatment of choice is penicillin and drainage of infected pleural fluid. The disease appears similar to other forms of bacterial empyema, although in some patients, a fulminant, fatal course may be seen. PMID- 6251998 TI - Enhanced growth hormone response to clonidine in the spontaneously hypertensive rat. AB - Plasma concentrations of growth hormone (GH) were measured after administration of clonidine (0.5 mg/kg) to spontaneously hypertensive (SH) rats and normotensive Wistar Kyoto controls. All rats were pretreated with reserpine (10 mg/kg). The GH response to clonidine was significantly higher in SH rats than in controls, indicating that in SH rats the responsiveness of post-synaptic alpha-adrenergic structures in the hypothalamus may be increased. PMID- 6251999 TI - [Preliminary observation on respiratory infection of Pseudomonas aeruginosa treated with ultrasonic aerosol inhalation of polymyxin B (author's transl)]. PMID- 6252001 TI - [Lung carcinoma in young adults. A clinico-pathologic analysis of 30 cases (author's transl)]. PMID- 6252000 TI - Anomalous plasma cyclic AMP responses to glucagon in patients with liver disease. AB - The purpose of the present study is to show anomalies of the plasma cAMP response of patients with hepatic disorders to a single injection of a low dose of glucagon (1 microgram/kg body wt). The response was markedly blunted in patients with liver cirrhosis and potentiated in patients with acute or chronic hepatitis. This glucagon test is, therefore, promising for development as a simple diagnostic means without undertaking liver biopsy to distinguish cirrhosis from chronic hepatitis. PMID- 6252002 TI - [Site-specific deletions of vector plasmid pBR322]. PMID- 6252003 TI - [Cloning simian adenovirus 7 DNA fragments in Escherichia coli bacteria using plasmid vector pBR322]. PMID- 6252004 TI - [Inhibitory action of newly synthesized 1,3-dimethylxanthine derivatives on the 3',5'-cyclic AMP phosphodiesterase activity of the homogenates of various tissues]. AB - The authors examined the action of fine newly synthesized xanthine derivatives on the activity of the enzyme 3',5' AMP phosphodiesterase (at high substrate concentrations) in homogenates, obtained from the brain lung and myocardium of a rat. The compounds were compared with theophylline for their activity. They showed low inhibiting activity in brain homogenates in contrast to the manifested activity of some of them in lungs and myocardium. Especially manifested difference was observed for the compound with a code 1t which was find times stronger inhibitor in the lung than in the brain. The authors make an inference that some of the compounds manifect selective activity as inhibitors of the enzyme phosphodiesterase and in this sense the search for xanthine derivatives with specific activity is prespective. PMID- 6252005 TI - Neuromuscular junction transmission deficit in a patient with primary hyperparathyroidism. PMID- 6252006 TI - Ouabain effects on hormonally-stimulated bone resorption and cyclic AMP content in cultured fetal rat bones. AB - Ouabain in concentrations from 20-100 micromoles produced a dose-related inhibition of in vitro stimulation of bone resorption by parathyroid hormone, 1,25-dihydroxyvitamin D3 and calcium ionophore A23187, as measured by 45Ca and [3H]-hydroxyproline release in 5-day cultures of fetal rat forelimb rudiments. The inhibitory effect on 45Ca release was completely reversed by subsequent incubation in ouabain-free medium. At a concentration of 100 micromoles ouabain virtually abolished active bone resorption; however, basal and stimulated bone cyclic AMP (cAMP) content were significantly increased above levels observed in the absence of ouabain. The increased cAMP content did not appear to be the result of phosphodiesterase inhibition. It is concluded that intact Na/K ATPase function is required for hormonally-stimulated bone resorptive processes and that the inhibitory effect of ouabain on bone resorption is produced at a point subsequent to cyclic AMP generation. PMID- 6252007 TI - Effect of dopaminergic and GABA-ergic drugs given alone or in combination on the anticonvulsant action of phenobarbital and diphenylhydantoin in the electroshock test in mice. AB - In the electroshock test--taking hind-limb tonic extension as the end point- apomorphine (10 mg/kg) exerted no effect on the anticonvulsant action of phenobarbital (PB; 20 mg/kg) or diphenylhydantoin (DPH; 8 mg/kg); amantadine (25 and 100 mg/kg) decreased that of DPH, while L-DOPA (500 mg/kg) and d,l amphetamine (10 mg/kg) potentiated the action of both anticonvulsants. Fluphenazine (4 mg/kg) had no influence on the effects of the two anticonvulsants, but haloperidol lessened that of DPH. All GABA-ergic stimulants used, i.e., gamma-hydroxybutyric acid (GHBA/250 mg/kg), baclofen (2.5 and 10 mg/kg) and aminooxoacetic acid (AOAA; 15 and 20 mg/kg) potentiated the action of PB; the action of DHP was unaffected by these drugs except for AOAA (20 mg/kg). The combined treatment with dopaminergic and GABA-ergic stimulants, being ineffective in terms of anticonvulsant activity, resulted in a marked potentiation of the action of the anticonvulsants tested in this study. The most distinct potentiation was noted in the case of PB, baclofen (1 mg/kg), and amantadine (25 mg/kg). PMID- 6252008 TI - Mechanisms of interaction of asymmetrical bilateral epileptogenic foci in neocortex. AB - The mechanisms of interaction of bilateral asymmetrical foci on cat neocortex were studied with varying concentrations of the epileptogenic agent and with callosal splitting and cortical-callosal isolation. When epilepsy was severe, a facilitatory interaction occurred. This was the result of two opposing mechanisms simultaneously operating, namely a transcallosal inhibitory mechanism and a predominant facilitatory subcortical mechanism. When epilepsy was less intense, subcortical structures were not involved and only the inhibitory transcallosal mechanism was at work, leading to an inhibitory interaction. The conclusion is put forward that two asymmetrical cortical foci do not necessarily interact in only one simple way. Their type of interaction (facilitatory or inhibitory) depends on the pathways involved in the interaction and this, in turn, depends on the severity of epilepsy. PMID- 6252009 TI - The effect of quartz, administered by intratracheal instillation, on the rat lung. I. The cellular response. PMID- 6252010 TI - Evidence of a quartz-induced chemotactic factor for guinea pig alveolar macrophages. PMID- 6252011 TI - Studies of microsomal glucose-6-phosphatase on liver of irradiated rats. AB - The activity of microsomal glucose-6-phosphatase (EC 3.1.3.9) on male rat liver was measured 1-9 days after whole-body gamma-irradiation. A marked fall of activity, expressed per whole liver, was observed reaching a minimum on the 4th day following irradiation. The enzyme activity is partially and momentarily restored (on day 7), before a new decrease occurred. Furthermore, when the results are expressed per milligram of microsomal proteins, there was no change. Cysteamine, when injected in vivo, kept up the glucose-6-phosphatase of whole liver. On day 4, a histochemical demonstration of the enzyme in liver cells is in accordance with enzyme measures. These observations suggested that the enzyme quantity was altered during the acute radiation syndrome in the rat. PMID- 6252012 TI - Phosphorylating-dephosphorylating enzymes of avian oviductal secretions. AB - Avian oviductal fluids contain phosphorylating-dephosphorylating enzymes that might function in sperm-oocyte interactions. Phosphorprotein phosphatase and protein kinase have been purified 20-fold and 40-fold, respectively. The latter easily aggregates and is highly labile. Other properties are comparable to those of holoenzymes. PMID- 6252014 TI - alpha 1- and alpha 2-vascular adrenoceptors in the dog. AB - Prazosin inhibited contractions of isolated electrically stimulated dog pulmonary artery preincubated with (-)-7-3H-norepinephrine, but had no effect on 3H overflow, whereas yohimbine enhanced both responses. In pithed dogs the cumulative doses of yohimbine required for 50% inhibition of the pressor effects of clonidine, phenylephrine and norepinephrine were 23, 188 and 35 micrograms/kg i.v., and those for prazosin were 9, 1.5 and 5 micrograms/kg i.v., respectively. The agonists could be ranked in pairs depending on the extent to which the antagonists discriminated members of the pair: clonidine-phenylephrine > phenylephrine-norepinephrine > clonidine-norepinephrine. The results suggest that pressor effects in dogs are mediated by both alpha 1- and alpha 2-vascular (i.e. postsynaptic) adrenoceptors. PMID- 6252013 TI - Pharmacological characterization of neurotensin receptors in the rat isolated portal vein using analogues and fragments of neurotensin. AB - The contractile effects of the tridecapeptide neurotensin (NT) and several NT fragments and analogues were evaluated and compared in the rat isolated portal vein. The removal of the sequence pGlu1-Leu2-Tyr3-Glu4-Asn5-Lys6-Pro7 produced practically no change in the myotropic activity of NT while the deletion of Leu13 or the last 3 C-terminal amino acids (e.g. Tyr11, Ile12 and Leu13) gave compounds with very low agonist activity (NT(1-12)) or devoid completely of affinity and intrinsic activity (NT(1-10)). Replacing Tyr11 with Ala, Leu, D-Tyr or D-Phe markedly decreased the stimulant effect of NT but did not confer to the molecule antagonistic properties. On the other hand, the substitution of Try11 with D-Trp or Tyr(Me) gave NT analogues which behave as specific and competitive antagonist of the contractile effect of NT in the portal vein. pA2 values of [D-Trp11]-NT and [Tyr(Me)11]-NT measured in the venous preparation were similar to those found in the coronary vasculature of the rat. Taken all together, these results suggest that: (1) the minimum structure required for the full expression of the myotropic activity of NT in the rat portal vein is -Arg9-Pro10-Tyr11-Ile12-Leu13-OH; (2) Tyr11 appears to be closely involved in the process of NT receptor activation since its replacement with D-Trp or Tyr(Me) produced specific and competitive antagonist of NT; (3) the receptors mediating the contractile effect of NT in the rat portal vein appear to be pharmacologically similar to those found in the coronary vessels of the rat. The possibility for the existence of different types of NT receptor in other tissues is discussed. PMID- 6252015 TI - Opiate receptors may mediate the suppressive but not the excitatory action of ACTH on motor activity in rats. AB - Subcutaneous injections of adrenocorticotropin (ACTH) or of the opiate antagonist naltrexone produced a one (2.0 mg/kg) dpressed, whereas smaller doses of ACTH (50 micrograms/kg) and of naltrexone (0.125 and 0.25 mg/kg) stimulated motor activity in the open field test. Furthermore, naltrexone at a dose level that had no effect on motor activity blocked the suppressive effect of the high doses of ACTH but had no effect on the stimulating effect of the intermediate dose of ACTH. Finally, chronic naltrexone administration resulted in enhanced sensitivity to the suppressive but not to the stimulating effect of ACTH on motor activity. It is argued that opiate receptors may play a selective role in the effect of ACTH on motor activity. Such receptors may mediate the supressive effect of high doses of ACTH whereas other, naltrexone insensitive receptor systems may mediate the stimulating effect of ACTH on activity functions. PMID- 6252016 TI - Diminished purinergic modulation of the vascular adrenergic neurotransmission in spontaneously hypertensive rats. AB - The inhibitory effects of adenosine and ATP on the pressor response of the perfused mesenteric vascular bed to perivascular adrenergic nerve stimulation were compared between spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKR). Both adenosine and ATP inhibited the neurogenic vasoconstriction in a dose-dependent manner in WKR, in which the inhibitory effect of adenosine was approximately eight times greater than that of ATP on the basis of 50% inhibitory doses (ID50). In the same preparation isolated from SHR, the inhibitory effects of both adenosine and ATP were significatly smaller than that in WKR. The ID50 values in the SHR for both agonists were approximately six times those found in WKR. These compounds also inhibited the pressor response to norepinephrine (0.3 microgram/ml) infusion, but the degrees of inhibition were markedly less than those with the neurogenic pressor response, and were not significantly different between WKR and SHR. These results suggest that presynaptic inhibition of vascular adrenergic neurotransmission by purine compounds is reduced in SHR. PMID- 6252017 TI - Evidence for a direct inhibitory effect of morphine on the secretion of posterior pituitary hormones. AB - The effect of morphine and naloxone on vasopressin and oxytocin release from incubated neurointermediate lobe and pars nervosa of rat pituitaries were investigated. It was shown that morphine and endorphins blocked hormonal output and that this inhibitory action was reversed by naloxone. It is concluded that opiates exert a direct inhibitory influence on vasopressin and oxytocin secretions from the neurohypophysis. PMID- 6252018 TI - Regulation of receptor binding interactions of 125I-angiotensin II and 125I [sarcosine1,leucine8]angiotensin II, an angiotensin antagonist, by sodium ion. AB - Angiotensin receptor binding interactions of the angiotensin agonist, 125I angiotensin II (125I-AII), and antagonist, 125I-[sarcosine1,leucine8]angiotensin II (125I[Sar1,Leu8]AII), are differentially affected by sodium ion concentration. 125I-AII binding to calf cerebellar cortex or adrenal cortex is increased 25 or 2.5 fold respectively when sodium ion concentration is increased from 10 to 150 mM. In brain membranes increasing sodium concentration accelerates the association and slows the dissociation of 125I-AII. 125I[Sar1,Leu8]AII binding to these tissues is much less sensitive to changes in sodium ion concentration. In rabbit uterine homogenates, neither 125I-AII nor 125I[Sar1,Leu8]AII binding is significantly altered by changes in sodium ion concentration. The sodium elicited increase in 125I-AII binding to calf cerebellum is correlated with cationic size and is not an ionic strength effect. The effect of sodium on potencies of angiotensin analogues in competing for 125I[Sar1,Leu8]AII binding does not correlate with agonist or antagonist properties, but is largest for peptides with aspartic acid at position one in the peptide structure. PMID- 6252019 TI - Receptor binding interactions of the angiotensin II antagonist, 125I [sarcosine1,leucine8]angiotensin II, with mammalian brain and peripheral tissues. AB - Sarcosine1,leucine8-angiotensin II ([Sar1,Leu8]AII), an angiotensin II antagonist, binds saturably, reversibly and with high affinity (KD's of 0.03-22 nM) to calf cerebellar cortex, bovine adrenal cortex and rabbit uterine membranes. The peptide specificity of 125I[Sar1,Leu8]AII binding to brain, adrenal cortex and uterus is consistent with the labeling of physiologically relevant angiotensin receptors. A detailed study of the binding potencies of 28 angiotensin peptide analogues reveals: (1) very significant correlations between peptide binding potencies at 125I-AII compared to 125I-[Sar1,Leu8]AII binding sites, (2) many similarities between brain and uterine receptor sites and marked differences between these two tissue receptors compared to adrenal cortical receptor sites, and (3) correlations among peptide physiological potencies (AII contracted rabbit aortic strip) and receptor binding potencies in all three tissues labeled with either 125I-AII or 125I-[Sar1,Leu8]AII. The correlations are much better for adrenal cortex than for brain or uterus, suggesting that adrenal cortical angiotensin receptors are similar to aorta angiotensin receptors. PMID- 6252020 TI - Chronic heart failure in the guinea pig increases cardiac alpha 1- and beta adrenoceptors. AB - Compared with sham-operated guinea pigs, chronic heart failure produced by aortic constriction resulted in a 79% increase in alpha 1-adrenoceptor density as measured by [3H]prazosin binding (73 +/- 15 vs. 131 +/- 20 fmol/mg protein, P < 0.05); beta-adrenoceptor number, measured by (-)-[3H]dihydroalprenolol binding, increased by 93% (28 +/- 3.4 vs. 54 +/- 5.2 fmol/mg protein, P < 0.01). For each radioligand KD values were unchanged. Thus, congestive heart failure due to chronic pressure overload results in compensatory augmentation of alpha 1- and beta-adrenoceptor numbers. PMID- 6252021 TI - A novel GABA receptor modulates stimulus-induced glutamate release from cortico striatal terminals. AB - The possibility of there being a population of GABA receptors located on cortico striatal terminals is suggested by [3H]GABA binding studies. Experiments carried out to investigate the stimulus-induced release of glutamate from cortico striatal terminals revealed an active modulation by a presynaptic GABA receptor. The differential responses of this receptor to a range of GABA agonists suggest that it may represent a novel type of GABA receptor. PMID- 6252022 TI - Effects of desipramine and yohimbine on alpha 2- and beta-adrenoreceptor sensitivity. AB - The effects of yohimbine on desipramine-induced adrenoreceptor alterations were examined in murine limbic forebrain areas. Treatment with both drugs in combination resulted in a significant decrease in [3H]dihydroalprenolol binding, which was not manifest after treatment with either drug alone. Moreover, co administration of yohimbine was found to accelerate the time course and increase the magnitude of desipramine-induced increases in [3H]clonidine binding. The possible physiologic significance of these findings is discussed along with their pharmacologic implications. PMID- 6252023 TI - Harmaline-induced tremor: the benzodiazepine receptor as a site of action. AB - Harmaline produces a tremor which is prevented by diazepam. This beta-carboline also displaces specifically bound 3H-flunitrazepam from the benzodiazepine receptor. While harmaline has a low affinity for the receptor (IC50 approximately 600 micro M), tremorogenic (i.p.) doses of harmaline produce brain concentrations sufficient to occupy some benzodiazepine binding sites. It is suggested that part of harmaline's actions may be the results of an interaction with the benzodiazepine receptor. PMID- 6252024 TI - Analgesic action of intrathecal and intracerebral beta-endorphin in rats: comparison with morphine. AB - beta-Endorphin and morphine were given into the nucleus reticularis gigantocellularis (NRGC), spinal subarachnoid space and third ventricle of rats, and the antinociceptive effects were assessed by the tail-pinch method. The NRGC was 4-5 times as sensitive to beta-endorphin as was the spinal subarachnoid space and third ventricle, while the NRGC was 13-19 times as sensitive to morphine as were the other regions. Thus, it would appear that beta-endorphin has more sites of action for the production of analgesia than does morphine. PMID- 6252025 TI - Activation of presynaptic alpha-noradrenaline receptors in rat brain by the potent dopamine-mimetic N,N-dipropyl-5,6-ADTN. AB - Rat cerebral cortex slices labeled with 3H-noradrenaline (NA) were superfused and 3H-NA release was induced with 20 mM K+. The release of 3H-NA was not affected by DA (1 micro M), but was inhibited by the 2-aminotetralins, 5,6-ADTN and N,N dipropyl-5,6-ADTN (at a concentration of 1 micro M) by about 27% and 65%, respectively. The inhibitory effect of N,N-dipropyl-5,6-ADTN was concentration dependent (3 x 10(-8) to 3 x 10(-7) M) and was antagonized by phentolamine but not by fluphenazine. The data indicate that, in addition to activating dopamine receptors, N,N-dipropyl-5,6-ADTN stimulates presynaptic alpha-NA receptors. PMID- 6252026 TI - Effects of prostaglandin D3 on nerve transmission in nictitating membrane of cats. AB - In anesthetized cats, intra-arterial injection of PGD3 toward the nictitating membrane caused long-lasting, dose-related decreases in the response of the nictitating membrane to sympathetic nerve stimulation. During peak depression of nerve transmission the response of the nictitating membrane to intra-arterial norepinephrine was not depressed suggesting that PGD3 suppressed the release of norepinephrine. PGD3 was as potent as PGD2 for modulating sympathetic nerve transmission but was less effective in activating a vagally mediated bradycardia. The results show that the PGD3 can modulate autonomic nerve transmission. PMID- 6252027 TI - The striatonigral GABA pathway: functional and neurochemical characteristics in rats with unilateral striatal kainic acid lesions. AB - Rats with unilateral striatal kainic acid (KA) lesions showed ipsilateral rotation to subcutaneous apomorphine, contralateral rotation to intranigral muscimol and reductions in striatal glutamic acid decarboxylase (GAD) activity and nigral gamma-aminobutyric acid (GABA) concentration. Rotational responses to apomorphine were highly correlated with nigral GABA depletions, and were a sensitive index of the functional integrity of striatonigral GABA neurons. Rotational responses to muscimol were also correlated with nigral GABA depletions, consistent with supersensitivity of denervated nigral GABA receptors. Striatal GAD was not correlated with either behavioural measure or with nigral GABA, and was a poor index of striatonigral function. These results are discussed in terms of (i) the functional role and adaptive capacity of striatonigral GABA neurons in linking the striatum with its effector mechanisms, (ii) parallels between parameters in GABA-dependent and DA-dependent rotational models and (iii) the status of the striatal KA lesion as a model for Huntington's disease and other extrapyramidal movement disorders. PMID- 6252028 TI - Effect of the time interval between blood sampling and assay on serum angiotensin I-converting enzyme activity from captopril-treated rats. AB - Intra-arterial injection of captopril (1 mg/kg) effectively lowered arterial blood pressure in aorta-coarcted hypertensive rats along with an associated reduction of serum angiotensin I-converting enzyme (ACE) activity. ACE activity in serum samples from captopril-treated animals that were assayed within 60 min after collection was inhibited 93%. However, this inhibition progressively decreased as the interval between time of assay and blood collection increased. This information would appear to be of considerable value in planning experiments for the determination of serum ACE activity from captopril-treated animals. PMID- 6252029 TI - Evidence for a GABAergic nigrothalamic pathway in the rat. I. Behavioural and biochemical studies. AB - Unilateral stereotaxic microinjection of muscimol into the caudal region of the substantia nigra (SN) evoked tight, dose-related contralateral locomotor asymmetry and stereotypy. These behaviours were partially attenuated by various pretreatments, including 6-hydroxydopamine lesions of the nigrostriatal dopamine pathway, intraperitoneal (i.p.) haloperidol, and inhibition of thalamic GABA transaminase activity by local intrathalamic injection of ethanolamine-O sulphate. Electrolytic or kainic acid lesions of the medial thalamic nuclei (MTN) partially reduced the contraversive rotation to intranigral muscimol, and completely abolished the similar behaviour elicited by apomorphine (25 microgram) injected into the ipsilateral caudate nucleus. Contraversive turning to intranigral muscimol was completely inhibited by kainic acid lesions of the ipsilateral SN, but potentiated by intrahalamic injection of picrotoxin. Muscimol (40 ng--4 microgram) administered to the MTN complex in one hemisphere stimulated rats to move in ipsilateral circles that were unaffected by haloperidol. The results of these behavioural experiments suggest that the nigrostriatal dopamine pathway, the nigrothalamic projection and possibly other non-dopaminergic SN efferents all play important roles in mediating the influences of the SN on motor and stereotyped behaviours. Disruption of the nigrothalamic pathway following electrical or chemical injury to the SN was accompanied by falls in GABA and its synthesising enzyme in the corresponding MTN. These data, together with the findings of our electrophysiological study presented in the following paper, are consistent with the nigrothalamic system having a GABAergic inhibitory function. PMID- 6252030 TI - Evidence for a GABAergic nigrothalamic pathway in the rat. II. Electrophysiological studies. AB - Extracellular recordings were made from neurones in the ventromedial and parafasicular nuclei of the rat thalamus, many of which had demonstrable capsular or caudate projections. These cells responded to electrical stimulation of the ipsilateral substantia nigra with a short latency (4 ms) inhibition presumed to be monosynaptic. This inhibitory response was often preceded by a brief period of increased excitability (latency approximately 3 ms) attributed to activation of corticofugal collaterals. Longer latency, presumably oligosynaptic excitations (latency approximately 8 ms) and inhibitions (approximately 18 ms) were also obtained, but were more commonly evoked in non-projection neurones. All units were inhibited by iontophoretically applied GABA, glycine or 5-HT. Short and long latency synaptic and GABA-induced inhibitions were selectively blocked by bicuculline. Strychnine only antagonised glycine, while 5-HT was not affected by either convulsant. Intranigral injection of muscimol greatly elevated the spontaneous discharge rate of thalamic neurones, particularly those with a striatal projection. These data are compatible with nigrothalamic neurones maintaining a tonically active, GABA-mediated inhibition of cells in the ventromedial and parafascicular nuclei of the thalamus. It is speculated that intranigral muscimol indirectly activates these thalamic cells and thereby initiates contraversive circling behaviour by suppressing this inhibitory system. PMID- 6252031 TI - Effect of contraceptive steroids on gamma-aminobutyric acid metabolism and pyridoxal kinase activity in rat brain. PMID- 6252032 TI - Intact peripheral target essential for branching of developing nerve fibers. PMID- 6252033 TI - May K+ ions stimulate the formation of cyclic AMP in the brain independently on their depolarizing action? AB - The effect of potassium ions on the formation of adenosine 3',5'-monophosphate (cAMP) in the rat cerebral cortex in vivo was studied under conditions where development of spreading depression had been blocked by pretreatment of the cerebral cortex by topically applied magnesium ions. A linear relationship between potassium concentrations applied to the cortical surface and levels of cAMP has been found. Moreover, potentiation of the K+-effect by magnesium ions has been observed. PMID- 6252034 TI - Stimulation of pyruvate carboxylation by gastric secretagogues. AB - Pyruvate carboxylation was stimulated by 2 gastric secretagogues, histamine and dibutyryl cyclic AMP, and by butyrate. Thiocyanate, an inhibitor of acid secretion, produced a slight decrease. Avidin significantly reduced acid secretion and this effect was overcome by biotin and oxalacetate. The results suggest that carboxylation of pyruvate is one of the reactions controlling oxidative metabolism and acid secretion in toad gastric mucosa. PMID- 6252035 TI - Age-related differences in the urinary excretion of prostaglandin F2 alpha catabolites in the rat. AB - Tritium-labeled PGF2 alpha was administered i.v. into rats of varying ages (2, 4, 6 weeks and adult). Urine was collected and assayed for radioactive products by thin-layer-chromatography. Results showed a distinctly different urinary profile between the 2-week-old and the adult rat. While the urinary pattern from the 2 week-old rat gave a single less polar product than PGF2 alpha, the pattern from the adult rat gave products more polar than PGF2 alpha. Urine from the 4- and 6 week-old rats gave a mixture of these types of products. These results indicate that some prostaglandin catabolic pathway (likely the omega-oxidative system) is activated in vivo within the 4-6 week postnatal period in the rat. PMID- 6252036 TI - Effect of fasting on the lipid composition and enzyme activity of rat liver plasma membranes. AB - After 24-h fasting, when the recovery of plasma membrane protein isolated from rat liver was unchanged, the enrichment in 5'-nucleotidase was decreased by 16%. Modifications of the lipid composition were also observed and resulted in a 27% decrease of the cholesterol/phospholipid molar ratio. PMID- 6252037 TI - Brain cyclic nucleotide and energy metabolite responses to subanesthetic and anesthetic concentrations of halothane. AB - Adult rats were exposed to 0.5, 1.0 and 1.5% halothane, delivered in air, for 1 h. Whole brain 3',5'-cyclic adenosine monophosphate (cAMP) of halothane-exposed rats showed only a slight increase relative to control values. 3',5'-Cyclic guanosine monophosphate (cGMP) was increased significantly in halothane-exposed rats, and the response was directly related to the halothane concentrations. Adenosine triphosphate (ATP) and phosphocreatine (PC) remained unchanged relative to control values. Correspondence of these values to apparent discrepancies in the literature is discussed. PMID- 6252038 TI - Methionine enkephalin inhibits the bursting activity of the Br-type neuron in Helix pomatia L. AB - The present study demonstrates that methionine enkephalin can inhibit the normal bursting activity pattern of the RPal or Br-type neuron and this inhibition can be blocked by prior treatment with naloxone, the selective opiate antagonist. The study demonstrates indirectly the presence of opiate-like receptors in Helix pomatia. PMID- 6252039 TI - In vitro inactivation of gonadotropin receptors, a membrane-associated action? AB - Under in vitro conditions the time-dependent inactivation process of LH/HCG receptors is nearly identical in ovarian and testicular homogenates but different in gonadal membrane preparations. In the ovarian membranes the loss of binding sites during the first preincubation time is faster than in testicular membranes, especially in membranes of luteinized rat ovaries. Compared with the homogenates, however, the receptor-inactivation in the membranes is generally delayed. The inhibitory effect of metabolic agents on receptor inactivation indicates that membrane-associated actions are involved in this process. PMID- 6252040 TI - Localization of SV40 T antigen in mitotic cells by an immunoperoxidase method. AB - The immunoperoxidase technique has clearly demonstrated that SV 40 T antigen is dissociated from the chromosomes in mitotic cells, and massive transport of T antigen from the cytoplasm to the nucleus appears to take place during or immediately after the telophase. PMID- 6252041 TI - 5'-Nucleotidase activity in liver homogenates of rats treated with CCl4, colchicine, cycloheximide, emetine, ethanol, ethionine and 5-fluorotryptophan. AB - 5'-Nucleotidase activity an enzyme marker of the plasma membranes, increases in female rat liver homogenates following ethionine administration, while homogenates from males show no changes. Treatment with CCl4, colchicine, cycloheximide, emetine, ethanol and 5-fluorotryptophan does not significantly modify the 5'-nucleotidase activity of liver homogenates of either female or male rats. PMID- 6252042 TI - The mechanical and biochemical effects of pentoxifylline on the perfused rat heart. AB - Perfusion of the isolated rat heart at constant heart rate and coronary flow with the inhibitor of cyclic nucleotide phosphodiesterase, pentoxifylline (10(-4) moles/l), produced no significant effect on the maximum rate and the peak of contraction, but increased the maximum rate of relaxation. cAMP level and cAMP dependent protein kinase activity were increased in the absence of changes in cGMP. The results were identical in hearts of reserpinized rats. PMID- 6252044 TI - Plasma cyclic 3',5'-guanosine monophosphate and cyclic 3',5'-adenosine monophosphate response to methacholine in man. AB - Cholinergic agents are known to induce increases in tissue and plasma levels of cyclic GMP in experimental animals. We observed that i.m. injection of methacholine, a cholinergic agent, caused significant increases in plasma cyclic GMP and cyclic AMP in man. PMID- 6252043 TI - Effects of dobutamine on cyclic AMP accumulation induced by the stimulation of dopamine receptors in rabbit retina in vitro. AB - Intact rabbit retinae were used for testing in vitro the potential activation of dopamine receptors by a new cardioactive sympathetic amine dobutamine. It was found that despite the structure relationship of dobutamine with other dopamine analog, the pharmacological action of this compound is not comparable to that of apomorphine, N-methyl-dopamine and/or ADTN. PMID- 6252045 TI - Inhibition by bran of the colonic cocarcinogenicity of bile salts in rats given dimethylhydrazine. PMID- 6252046 TI - Reflections on the mechanism of action of hormones. PMID- 6252047 TI - Mechanisms of 'inducer exclusion' by glucose. PMID- 6252048 TI - Control of lactose transport in Escherichia coli. PMID- 6252049 TI - Relationship of free cytoplasmic pyrophosphate to liver glucose content and total pyrophosphate to cytoplasmic phosphorylation potential. PMID- 6252051 TI - The replacement of serum by SiO2 (aerosil) and 2-mercaptoethanol or diethanoldisulfide in the immunization and stimulation of spleen cell cultures. PMID- 6252050 TI - Stabilization of partially-purified glucose 6-phosphatase by fluoride. Is enzyme inactivation caused by dephosphorylation? PMID- 6252052 TI - 5'-nucleotidase activity of two populations of mouse thymocytes separated by peanut agglutinin agglutination. PMID- 6252053 TI - Charge isomers of simian virus 40 T-antigen. PMID- 6252054 TI - D-Tyr--Ser-Gly--Phe--Leu--Thr, a highly preferential ligand for delta-opiate receptors. PMID- 6252055 TI - A cytotoxic epidermal growth factor cross-linked to diphtheria toxin A-fragment. PMID- 6252056 TI - Bifunctional enkephalin analogues for affinity separation purposes. PMID- 6252057 TI - Distance determinations at the active site of kidney (Na+ + K+)-ATPase by Mn(II) ion electron paramagnetic resonance. PMID- 6252058 TI - A new type of AT-specific ligand constructed of two netropsin-like molecules. PMID- 6252059 TI - In vitro phosphorylation of histones H5, H2A, H2B and of the dimer H2A--H2B by a cyclic AMP-dependent protein kinase from rat pancreas. PMID- 6252060 TI - Chemotaxis. PMID- 6252061 TI - Complexities of transmission in autonomic ganglia. Introduction. PMID- 6252062 TI - The action of cAMP and catecholamines in mammalian sympathetic ganglia. AB - Electrophysiological approaches using intracellular microelectrode techniques have failed to critically test the hypothesis that cyclic AMP (cAMP) mediates the slow inhibitory postsynpatic potential (IPSP). The slow IPSP is not readily elicited, and the resting membrane potential is relatively insensitive to application of catecholamines and adenine nucleotides. However, comprehensive studies of voltage-dependent events in postganglionic neurons reveal three Ca2+ dependent potentials that are quite sensitive to catecholamines and adenine nucleotides. The hyperpolarizing afterpotential, the action potential shoulder, and the Ca2+ spike are all inhibited by alpha-adrenergic agonists, adenosine, and cAMP. We have proposed that simulation of alpha-adrenergic and adenosine receptors on the post-synaptic membrane results in antagonism of an inward Ca2+ current. Further experimentation is necessary to determine if cAMO acts as a second messenger or only by activating an adenosine receptor. Preliminary studies suggest that catecholamines and adenine nucleotides have similar and potent actions on the terminals of preganglionic axons. Here, inhibition of Ca2+ influx results in reduced acetylcholine release but facilitates high-frequency cholinergic transmission. More quantitative biophysical and pharmacological studies are required to better characterize the synaptic mechanisms in sympathetic ganglia. PMID- 6252063 TI - Current hypotheses for the slow inhibitory postsynaptic potential in sympathetic ganglia. PMID- 6252065 TI - Benzodiazepines: a tool to explore the biochemical and neurophysiological basis of anxiety. PMID- 6252064 TI - Electrophysiological actions of benzodiazepines. AB - Electrophysiological investigations have revealed that benzodiazepines, applied either locally or systemically, reduce central nervous system excitability. The studies summarized here indicate that this depression of excitability by benzodiazepines is a result of an increase in gamma-aminobutyric acid (GABA) mediated inhibition. This increase in inhibition may result from benzodiazepines increasing the activity of some GABAergic neurons and also from a modulatory action of benzodiazepines on GABA actions at some postsynaptic receptor sites. The modulatory action is observed with doses of benzodiazepines that do not cause any direct effects on neuronal excitability or membrane polarization. Specificity tests indicate that benzodiazepines do not enhance inhibition mediated by glycine or monoamines such as norepinephrine or serotonin. Results of experiments with a convulsant benzodiazepine compound, which causes a specific reduction in GABA mediated inhibition, are also presented, The data are discussed in terms of a model in which the benzodiazepine receptor, the GABA receptor, and the chloride ionophore are functionally linked. Furthermore, it is proposed that some postsynaptic actions of GABA may be continually regulated by the occupancy of a benzodiazepine receptor, and that occupancy of the benzodiazepine receptor may be permissive for the GABA-elicited increase in chloride ion permeability. PMID- 6252066 TI - GABA-benzodiazepine interactions: physiological, pharmacological and developmental aspects. AB - Many of the pharmacological actions of the benzodiazepines can be attributed to their actions on gamma-aminobutyric acid (GABA) systms in the brain. Electrophysiological studies on dorsal raphe neurons indicate that the benzodiazepines act postsynaptically to potentiate GABAergic inhibition in this midbrain nucleus. Direct binding studies have shown that both in vitro and in vivo binding of [3H]diazepam to a specific high affinity benzodiazepine binding site in cerebral cortical tissue are enhanced by the direct in vitro addition of GABA and GABA agonists or by pretreatment of animals with GABA analogs and agents that elevate GABA levels in brain. Ontogenic development of [3H]diazepam binding in brain parallels the development of the sodium-independent [3H]GABA binding. The ability of GABA to enhance benzodiazepine binding is present throughout development and inversely related to age. These data suggest that there is a functionally significant interaction between the benzodiazepines and GABA throughout development and at maturity. A model is proposed to relate these interactions to conformational changes in a benzodiazepine/GABA/Cl- ionophore complex. PMID- 6252067 TI - A normal cumulative conception rate after human pituitary gonadotropin. AB - Forty consecutive women were treated with human pituitary gonadotropin to induce ovulation. Thirty-seven patients (93%) ovulated and thirty (75%) conceived on at least one occasion. The cumulative conception rate for the series equaled that of the general population. Women with a past history of anorexia nervosa had the shortest average time to pregnancy. Of patients who did not conceive, four represented failures of patient selection in that they withdrew from treatment for a variety of psychiatric and social reasons, and six represented failures of treatment, not becoming pregnant despite the induction of ovulation. It is concluded that realistic goals for a contemporary human gonadotropin program include induction of ovulation in all patients and a cumulative conception rate equal to that of the general community. PMID- 6252069 TI - [Effect of changes in the external concentration of sodium, chlorine, and potassium ions on subsequent depolarization of a single node of Ranvier of isolated nerve fibers]. AB - Change in external concentration of Na+ (from 0 to 240 mmol), Cl- (from 0 to 120 mmol), and K+ (from 2.5 to 10--30 mmol) had no significant effect on the negative trace potential in the Ranvier isthmus of Rana ridibunda. In K+-free Ringer's solution a trace hyperpolarization occurred. The negative trace potential of the isthmus increased in blockade of the membrane potassium channels with tetraethylammonium chloride or 4-aminopyrydine. PMID- 6252068 TI - Response of serum prolactin to catechol estrogen in the immature rat. AB - The response of serum prolactin to the catechol estrogens, 2-hydroxyestrone (2-OH E1) and 2-hydroxyestradiol (2-OH E2) and their primary estrogens, estrone (E1) and estradiol (E2), was studied in 35-day-old male rats. The subcutaneous administration of 50 microgram of 2-OH E1 or 2-OH E2 significantly suppressed serum prolactin concentrations, but they were not significantly altered by the administration of 50 microgram of E1 or E2. PMID- 6252070 TI - [Effect of potassium ions on electrogenesis and contraction of ureter smooth muscle]. AB - In the ureter smooth muscle cells, high--K solution produced a depolarization at the onset of which the action potentials (AP) and contraction occur; the latter consists of an initial phasic (Ph) and subsequent tonic (T) components. Ph component is initiated by the AP, T component--by a stable potassium depolarization. In Ca--free solution the AP, Ph and T components are blocked, although a sustained potassium depolarization is preserved. Basing on these results it is suggested that: 1) phasic contraction is initiated by calcium ions influxed via fast potential--dependent calcium channels participating in the AP generation; 2) tonic contraction is also initiated mainly by extracellular calcium influx through slow potential--dependent calcium channels of plasmatic membrane that appear to be similar to calcium channels of sarcoplasmic reticulum membrane in skeletal muscles and of the membrane of presinaptic nerve terminals. PMID- 6252071 TI - [Effect of manganese ions and verapamil on electrogenesis and contraction of ureter smooth muscle]. AB - Fast and slow calcium channels of the electrically excitable membrane of the ureter smooth muscle cells had different sensitivity to manganese ions and verapamil. Manganese ions (10(-4) M) selectively blocked the fast potential- dependent Ca--channels, Ca ions being necessary for phasic contraction, whereas verapamil (10(-9)--10(-8)) specifically blocked the slow potential--dependent CA- channels. PMID- 6252072 TI - [Effect of calcitonin on the electrical activity of the sinoatrial node and contractile myocardium of homeotherms]. AB - The effect of calcitonin on the AP parameters of different myocardium cells in rabbit and guinea pig is related to different significance of fast and slow flow channels for generation of different AP components. Thus, instead of enhancement of the AP amplitude revealed in the cells of the contractile myocardium of warm- and cold--blooded animals and related to stimulation of Na+ transport via fast Na+ channels, calcitonin induced a decrease in the AP amplitude of the heart pace -maker cells in rabbits. The calcitonin effects proved to be different in actions upon the authentic and the latent pace--maker cells. PMID- 6252073 TI - [Effect of catecholamines on the electrical and mechanical activity of frog myocardium after increasing the duration of action potentials with nickel ions]. AB - The "chemical current--clump" method revealed that, after nickel ions (0.5 mM) had produced prolongation of AP, catecholamines (CA) increased the force and shortened the relaxation phase of isometric tension in the frog ventricular myocardium. Additional blockade of Ca++--channels with 2 mM NiCl2 or niphedipin inversed the positive inotropic effect of CA. Prevention of the ability of CA to increase the Ca--current and AP--duration unmasks the action of CA on intracellular stores. PMID- 6252074 TI - [Role of the opiate receptors of different brain regions in the formation of emotional responses in rats]. PMID- 6252075 TI - [Excitatory postsynaptic potentials in motor neurons of rats upon stimulation of individual reticulospinal neurons]. AB - Unit reticulo-motoneuronal EPSPs evoked by extra -- or intracellular stimulation of reticulo-spinal neurons were recorded intracellularly from rat lumbar motoneurons. Reticular neurons with fast conducting axons revealed higher probability of direct effect on motoneurons. Terminals of single reticular neurons to different motoneurons were shown to be widely distributed. Analysis of the time course of average unit EPSPs suggests proximal to soma location of some reticulo-motoneuronal synapses. Amplitude-frequency histograms of the unit EPSPs could be fitted in most cases by Poisson's or binominal distribution, suggesting the quantal nature of transmitter release. PMID- 6252076 TI - [Age and the effect of noradrenaline on the physiologic properties and cyclic 3',5'-adenosine monophosphate content of portal vein smooth muscle cells]. AB - With ageing, the threshold doses of noradrenaline necessary for initial electric and contractile responses of the vessel smooth muscle cells, significantly decrease. The levels of cyclic 3'5' adenosinmonophosphorous acid (cAMP) in the portal vein's walls differ insignificantly in adult and old animals. The noradrenaline effect on the portal vein of old animals involves a more obvious increase in the cAMP content. The increased sensitivity of the vessel smooth muscle cells to noradrenaline in old animals seems to be due to the fact that in old animals the adenylatcyclase -- cAMP system responds to lesser amounts of noradrenaline. PMID- 6252077 TI - [ACTH receptors in human adrenocortical tumors (author's transl)]. PMID- 6252078 TI - A comparison of Na-K-ATPases obtained from brains of adult and fetal rats. PMID- 6252079 TI - Collagen prolyl hydroxylase activation in dermal cell primary cultures. PMID- 6252080 TI - Isolation of a plasma membrane fraction highly enriched in ouabain-sensitive Na+ K+-ATPase from rat brain white matter. PMID- 6252081 TI - Properties of gentamicin adenylyl transferase obtained from R-factor-resistant Escherichia coli. PMID- 6252082 TI - Enzymatic characterization of sarcolemmal membranes from the marine crab Carcinus maenas L. PMID- 6252083 TI - Recombinant DNA--a new source of insulin. PMID- 6252084 TI - Relationship between tumor formation and cell-mediated immunity in hamsters with transplanted HVJ (Sendai virus)-carrying tumor cells. AB - Using macrophage migration inhibition (MMI) and the cell-mediated cytotoxicity (CMC) test, the cell-mediated immune response in hamsters with transplanted HVJ carrying tumor cells (THEL-HVJ or THEL-HVJpits) was examined in relation to the lowered transplantability of the cells. The cells cultured at a temperature (34 degrees) permissive for HVJpits (temperature-sensitive HVJ) showed significantly lowered transplantability in hamsters. After shifting the cell culture temperature up to 39 degrees (non-permissive for HVJpits) for 5 days, THEL HVJpits cells which had lost their cellular HVJ antigens regained the same high transplantability observed in parent THEl cells. However, culture of the cells at 37 degrees (partially permissive) for 24 hr did not significantly affect their tumor-forming ability with lowered transplantability, in spite of a considerable reduction in cellular HVJ antigens. The MMI test on hamsters with transplanted THEL-HVJ or THEL-HVJpits cells cultured at 34 degrees (MMI/THEL-HVJ 24 or MMI/THEL-HVJpits 34) was more markedly positive, and for a longer period (1 to 4 weeks), than the same test on hamsters inoculated with THEL cells. However, the MMI/THEL-HVJpits 39 cells acquired lowered reactivity like those from THEL-tumor bearing animals, while MMI/THEL-HVJpits 37 cells were still positive, just as in MMI/THEL-HVJpits 34. In the CMC test, much more cytotoxic activity was observed in spleen cells from hamsters with transplanted THEL-HVJpits cells than in those from THEL-transplaned animals; there was a general correspondence with the results obtained in the above MMI test. These findings strongly indicate that the lowered transplantability of HVJ-carrying tumor cells may be due to a significant induction of cell-mediated immune responses. It is suggested that cell membrane antigens modified (xenogenized) by the complete or partial expression of HVJ genomes carried may play an important part in this induction in vivo. PMID- 6252085 TI - Fusion of transformed human cells by simian retroviruses. AB - Mason-Pfizer monkey virus (MPMV), baboon endogenous virus (BaEV) and simian sarcoma virus associated virus (SSAV) induced fusion in cultured human cells derived from tumors or transformed in vitro. Not only virus-transformed cells, but also cells transformed spontaneously by 4-nitroquinoline 1-oxide (4-NQO) treatment or by 60Co-gamma ray irradiation were fused by these simian retroviruses. Non-transformed cells derived from normal human embryos were not fused by any of these viruses. Of these tumor or transformed cells, cells carrying Rous sarcoma virus (RSV) genome were most extensively fused by these simian retroviruses. Anti-MPMV, anti-BaEV and anti-SSAV sera blocked the cell fusion mediated by MPMV, BaEV and SSAV, respectively, and not that by other viruses, indicating that the cell fusion was virus-specific. PMID- 6252086 TI - Electron spin resonance study on the metabolism of twelve monohydroxy benzo[alpha]pyrenes in liver microsomes. PMID- 6252087 TI - Radionuclide diagnosis of Meckel's diverticulum. AB - Meckel's diverticulum can be detected with a high degree of accuracy by radionuclide scintigraphy using technetium-99m pertechnetate. The technique is without risk and should precede roentgenographic studies when the diagnosis is suspected. The method is described and the causes for false positive and false negative examinations are discussed. False negatives are rare and false positive are usually secondary to other surgical entities. Overall accuracy is 85 to 90%. PMID- 6252088 TI - Angiographic diagnosis of a pancreatic islet tumor in a patient with the WDHA syndrome. AB - A patient with an islet cell tumor of the pancreas that produced the watery diarrhea, hypokalemia, achlorhydria (WDHA) syndrome is presented. On celiac angiography an extremely vascular mass was seen in the body of pancreas with hypertrophied arteries and persistent, dense tumor staining. PMID- 6252089 TI - Effects of dietary fiber on intestinal glucose absorption and glucose tolerance in rats. AB - The effects of acute and chronic dietary fiber (cellulose and pectin) supplementation on both intestinal glucose absorption and oral glucose tolerance were studied in rats. The effect of intraluminal fiber on intestinal glucose absorption was evaluated in perfused jejunal loops as was the effect of a single cellulose or pectin-supplemented meal on serum glucose responses to a carbohydrate load. Neither pectin nor cellulose impaired jejunal glucose absorption, but pectin did decrease serum glucose responses to an oral carbohydrate load. Chronic fiber supplementation significantly decreased intestinal glucose absorption in rats who had received for 5 wk a fiber-free diet supplemented with either cellulose (10%) or pectin (5%). Chronic supplementation with cellulose or pectin impaired intestinal glucose absorption and decreased serum glucose responses. These results suggest that differences in glucose homeostasis observed after ingestion of single high-fiber meals may be caused by viscosity-related delays in the rate of gastric emptying, whereas differences noted after chronic supplementation of dietary fiber are related to adaptive changes in the intestine. PMID- 6252090 TI - Adenoid cystic carcinoma of the esophagus. PMID- 6252091 TI - Endoscopic biopsy diagnosis of oat cell carcinoma of the lung penetrating the esophagus. PMID- 6252092 TI - Granular cell tumor (myoblastoma) of the large intestine removed by colonoscopy. PMID- 6252093 TI - [The role of endorphins in the perinatal period (author's transl)]. PMID- 6252094 TI - [Klippel-Trenaunay syndrome. A case report]. PMID- 6252095 TI - [The effect of wheat bran on partial intestinal function and metabolism]. PMID- 6252096 TI - The influence of neonatal stress on the physiological and behavioral response of lambs during active--avoidance conditioning. PMID- 6252097 TI - Increased cyclic AMP content directly correlated with morphological transformation of cells infected with a temperature-sensitive mutant of mouse sarcoma virus. AB - Normal rat kidney cells infected with a cold-sensitive mutant of mouse sarcoma virus [NRK(MSV-lb)] morphologically transform when exposed to adenosine 3':5' cyclic monophosphate (cAMP) at the restrictive temperature. The cAMP-induced morphological changes occur rapidly and are reversible. Agents capable of elevating endogenous levels of cAMP [prostaglandin E1 (PGE1) and cholera toxin (CT)] induced morphological transformation of NRK(MSV-lb) cells at the restrictive temperature that was concentration dependent, potentiated by cAMP phosphodiesterase inhibitors, and not prevented by inhibitors of DNA, RNA, and protein synthesis. Prostaglandin E1 stimulated a transient increase in the intracellular level of cAMP with a concomitant morphological transformation and reversion of cells as cAMP levels decline. The maximum increase is reached by 10 min, followed by a decline to near basal level by 80 min. In contrast, incubation of cells with CT resulted in irreversible morphological transformation and increased levels of cAMP first detectable by 1 hr with maximum levels reached by 24 hr. Heated CT (100 degrees C, 20 min) was without effect. Addition of CT to reverted PGE1-treated cells resulted in morphological transformation suggesting the existence of discrete receptors in NRK(MSV-lb) cells. PMID- 6252098 TI - Differences between rat liver epithelial cells and fibroblast cells in sensitivity to 8-azaguanine. PMID- 6252099 TI - Separation of human eosinophils in density gradients of polyvinylpyrrolidone coated silica gel (Percoll). AB - A method for isolation of eosinophils from human peripheral blood using isosmolar solutions of polyvinylpyrrolidone-coated silica gel (Percoll) is described. The purity ranged from 86 to 99% eosinophils in the final preparation and the recovery was 38-56%. The separation technique did not affect the viability or the metabolic capacities of the cells. PMID- 6252101 TI - Passage of poliovirus antibodies across the placental barrier. PMID- 6252100 TI - Characterization of responding cells in oxidative mitogen stimulation. III. Presence of I-A- and I-J, E, C-subregion gene products on the surface of required cells. AB - Ia antigens coded by genes of the murine major histocompatibility complex are expressed on the surface of a population of cells critical to the proliferative response of murine spleen cells to the oxidative mitogen neuraminidase/galactose oxidase. By selective depletion with antiserum and complement, Ia antigens coded (or determined) by the I-A and I-J, E, C subregions of the Ir region can be detected on the surface of cells required for the response. In addition, I-A subregion products have a functional significance in cellular activation which can be demonstrated by blocking experiments with anti-Ia serum in the absence of complement. PMID- 6252102 TI - Drug interaction studies on amphibian vasoconstrictor responses to mast cell degranulators. PMID- 6252103 TI - In vitro and in vivo inhibition of mast cell degranulation by a factor from Schistosoma mansoni. PMID- 6252104 TI - In vitro effects of histamine on eosinophil migration. AB - Histamine at concentrations of 5 X 10(-6) to 5 X 10(-5) M increased eosinophil movement to endotoxin-activated serum (EAS). This effect was due entirely to stimulation of random migration (chemokinesis). Directional motility (true chemotaxis) was inhibited by these concentrations. Regulation of chemotaxis was apparently mediated via an H2 receptor as metiamide, an H2 receptor antagonist, but not diphenylhydramine hydrochloride, an H1 receptor antagonist, blocked the histamine-induced inhibition of chemotaxis. Both histamine and metiamide when used alone had no effect on eosinophil motility. The histamine effects on motility were associated with increased levels of intracellular cAMP, whereas cGMP levels were not affected. PMID- 6252105 TI - Treatment of paracoccidioidomycosis, candidiasis, chromomycosis, lobomycosis, and mycetoma with ketoconazole. AB - The authors present the use of ketoconazole in 27 cases of paracoccidioidomycosis, eight of mycetoma, seven of chromomycosis, four of systemic candidiasis and one of lobomycosis. The drug was administered orally in a dosage of 200 to 400 mg per day within a period of up to 90 days. The results of the treatment for paracoccidioidomycosis were of cicatrization of the cutaneous lesions in three to four weeks in 24 patients and in two, from six to seven weeks. Out of 27 patients, 14 presented pulmonary lesions. The evolution within a 90-day period showed radiological cure in one case, improvement in seven, and unaltered picture in five patients. In one, there was no further control. In the three out of four cases of candidiasis there was clinical and mycological cure and in one case marked improvement. In seven cases of chromomycosis there was marked improvement in two, moderate in four, and slight in one case. There was slight improvement in one case of lobomycosis, and in eight cases of mycetoma moderate improvement in three, slight in three and none in two, but the mycological examinations were still positive. The drug tolerance was excellent. PMID- 6252106 TI - Nitrate and human cancer: a review of the evidence. AB - Nitrites, derived mainly from ingested nitrates, may react in vivo with secondary nitrogen compounds occurring naturally in certain foods to form N-nitroso compounds, which are potent carcinogens in laboratory animals. This paper reviews the mechanism of their formation and the evidence from epidemiological studies that high nitrate ingestion is involved in the aetiology of human cancer. PMID- 6252107 TI - Synthesis of human beta-endorphin in solution using benzyl-type side chain protective groups. AB - A solution synthesis of human beta-endorphin (beta-EP) was carried out by condensation of protected peptide segments bearing N alpha-tert.-butyloxycarbonyl groups and benzyl-derived groups for the protection of functionalities in amino acid side chains. Five intermediate segments were assembled in a stepwise manner starting at the carboxyl terminus. Thus, the segment of sequence region (27-31) was coupled to segment (22-26) by the azide method. Segment (19-21) was incorporated into the growing chain by azide coupling, and segment (10-18) by dicyclohexylcarbodiimide coupling in the presence of 1-hydroxybenzotriazole (DDC HOBt). Solubility problems in condensing the ensuing 22-peptide with segment (1 9) by DDC-HOBt were overcome by using a dimethylformamidephenol mixture as a solvent. Protecting group cleavage by Na in liquid NH3 was much superior to liquid HF which gave rise to many decomposition products. Homogeneous betah-EP indistinguishable from authentic material in physiochemical and biological properties, was obtained in a single preparative reversed phase liquid chromatographic step after protecting group cleavage. PMID- 6252108 TI - Separation of the dead cell fraction from X-irradiated rat thymocyte suspensions by density gradient centrifugation. PMID- 6252109 TI - The autoradiolytic and the gamma-induced demethylation of solid thymine-(methyl 14C). AB - The autoradiolytic and the gamma-induced demethylation of solid thymine were measured qualitatively and quantitatively for the first time with specially purified thymine-(methyl-14C). Analogous experiments with thymine-(methyl-3H) and radio-gaschromatographic analysis provided proof for the formation of molecular hydrogen and methane. Ethane was not detected. The results are discussed in connection with e.s.r.-spectroscopic studies. PMID- 6252110 TI - The reactions of l nm particles of plutonium-238 dioxide and curium-244 dioxide with lung fluid. AB - The reactions of 1 nm particles of plutonium-238 dioxide and curium-244 dioxide with rat lung fluid have been studied both in vitro and in vivo. The plutonium 238 particles are positively charged and combine by electrostatic attraction with the negative pulmonary surfactant which mediates the transfer of radioactivity to the blood. In contrast the curium-244 particles are negative and are assumed to diffuse passively through the alveolar walls. The results emphasise that electrostatic charge is an important factor governing the reaction of 1 nm actinide oxide particles with macromolecules. PMID- 6252111 TI - Ocular antiviral therapy. PMID- 6252112 TI - Evidence for a role of the plasminogen activator--plasmin system in corneal ulceration. AB - Plasminogen is present in the cornea andcan be activated to plasmin by plasminogen activator. Plasmin is able, in turn, to activate latent collagenase. This system could initiate and perpetuate the collagen degradation of corneal ulceration. This report details evidence for such a system in the cornea. Plasmin has been found to activate latent collagenase from organ cultures of ulcerating rabbit corneas and from fibroblast cultures derived from such corneas. As in the case of activation by trypsin, activation by plasmin results in the conversion of the 40,000 MW latent form to an active species of 23,000 MW. Explants of normal or alkali-burned, ulcerating corneas demonstrated plasminogen-dependent lysis of fibrin clots; frozen sections of such corneas demonstrated that lysis begins in the superficial stroma near the periphery of the cornea. Multiply freeze-thawed ulcerating corneas, but not normal corneas, showed initial lysis, not peripherally but at the ulcer region containing polymorphonuclear leukocytes. The fact that the peripheral lytic pattern existed in corneas that were obtained from eyes prefrozen in liquid nitrogen before excision of the corneas would suggest that plasminogen activator is normally contained in cells in vivo and is not made only in response to tissue injury. There was no correlation between the location of blood vessels or the presence of the corneal endothelium and the plasminogen dependent lysis. Plasminogen activator from the ulcerating cornea and from fibroblasts was characterized by sodium dodecyl sulfate--gel electrophoresis of its cleavage products of plasminogen. The activator cleaves plasminogen into heavy- and light-chain fragments similar to those produced from plasminogen by urokinase. Plasminogen activator activity was quantitated by a new assay that restricts diffusion of the enzyme to one dimension into a narrow bore tube. The addition of plasminogen daily to cultures of ulcerating corneas resulted in earlier rises of plasminogen activator, collagenase, and collagen degradation fragments in the culture media. Although total plasminogen activator levels were not increased by the addition of plasminogen to culture, levels of both collagenase and solubilized collagen were approximately doubled. It is concluded that the plasminogen activator--plasmin system might play an important role in the destruction of stromal matrix in corneal ulceration. PMID- 6252113 TI - Sensitivity of photoreceptors to elevated levels of cGMP in the human retina. AB - When isolated human retinas were cultured in the presence of a phosphodiesterase inhibitor or dibutyryl cyclic guanosine monophosphate (dbcGMP), degenerative changes occurred which were proportional to the concentration of drug used and the period of exposure. Low concentrations of either drug did not alter retinal morphology as compared to controls. Higher concentrations provoked vesiculation of rod inner segments and rounding up of cones. Numerous pyknotic nuclei were noted in the outer nuclear layer of those preparations. Combining IBMX and dbcGMP in the same medium destroyed virtually every rod in the specimen within 8 hr of incubation. Under those conditions, cones remained structurally intact although somewhat rounded. In all treatments, cells of the innerretinal layers maintained normal morphology. Our results suggest that elevated levels of cGMP in the human retina can alter certain metabolic processes in photoreceptors, which leads to degenerative changes and cell death uniquely in rod photoreceptors. PMID- 6252115 TI - Feline leukemia in Israel: prevalence of antibody to feline oncornavirus associated cell membrane antigen in stray cats. AB - Feline lymphoma was recorded for the first time in pet cats in Israel. Furthermore, a serological survey in urban stray cats was carried out to determine the prevalence of antibody to feline oncornavirus-associated cell membrane antigen (FOCMA). A total of 91 cats was tested and only 5 has antibody to FOCMA. Of these 5 positive cats, 4 originated from an area where a feline leukemia virus-positive cat had been detected prior to the survey. The prevalence of stray cats with antibody to FOCMA is lower in Israel than found in similar studies in the USA and Scotland. PMID- 6252114 TI - Simian virus nomenclature, 1980. AB - Approximately 75 simian viruses, counterparts of other animal viruses, are recognized. Nomenclature of these isolates, in general, consists of an SV (simian virus) or SA (simian agent) numerical series with no attempt to group them according to virus families. The biologic characteristics of these viruses indicate they may be classified into recognized families and groups. A simple sequential numerical designation is recommended as a nomenclature within virus families and groups. Finalization of nomenclature would follow approval by the Study Groups of the International Committee on Taxonomy of Viruses. PMID- 6252116 TI - Interaction of EBNA with anti-EBNA antibody and DNA. AB - Binding of Epstein-Barr-virus-determined nuclear antigen (EBNA) to acid-fixed nuclei could be prevented by exposing EBNA to anti-EBNA antibodies. While EBNA is eluted from acid-fixed nuclei by 0.4 M NaCl, it was not eluted even by 1.5 M NaCl if EBNA bound to acid-fixed nuclei had been exposed to anti-EBNA antibody. In this case the reaction was abolished, and EBNA was at least partially eluted by 0.2 M glycine buffer, pH 2.8, or by 3 M NaSCN. EBNA not exposed to antibody was completely eluted from acid-fixed nuclei by treatment with a solution containing 200 microgram of DNA per 1 ml of isotonic buffer, pH 6.5; however, after treatment with antibody, EBNA was not eluted by DNA. PMID- 6252117 TI - Early nuclear antigen as DNA-binding protein in cytomegalovirus-infected cells. AB - Early nuclear complement-fixing antigen in cytomegalovirus (CMV) (strain Ad 169) infected human embryonic fibroblasts is described. The nuclear antigen was solubilized from CMV-infected cells by high salt treatment. DNA-binding properties were studied by DNA-cellulose chromatography. The purified antigen, eluted from double-stranded DNA-cellulose columns, was added to acid-fixed nuclear preparations from human embryonic fibroblasts and then exposed to human sera containing antibodies to CMV. Positive staining was obtained by anti complement immunofluorescence. These data identify the CMV-determined nuclear antigen as a DNA-binding protein. In this respect, it is similar to the Epstein Barr virus nuclear antigen. PMID- 6252118 TI - Two-hit kinetics of focus formation in cells transfected with Rous sarcoma provirus. AB - DNA was purified from an established line of SR-E-transformed quail cells and was assayed for transfection in turkey cells. Transfection events were determined from foci of transformed cells growth under agar overlay which was used to prevent the spread of the progeny virus. It was found that transfection with Rous sarcoma proviruses follows two-hit kinetics, indicating that at least two (unlinked) provirus are required to give rise to a focus of transformed cells. PMID- 6252119 TI - Viral infection and acute peripheral facial palsy. A study with herpes simplex and varicella zoster viruses. AB - The role of herpes simplex virus (HSV) and varicella zoster virus (VZV) in acute peripheral facial palsy (APFP) was evaluated according to clinical symptomatology and serologic findings in a series of 70 patients seen over a one-year period. Peak morbidity of APFP occurred in the 21 to 30 years age group. Most patients were under 40 years of age and there were more female than male patients. Concomitant dysfunction of one or more other cranial nerves was present in most patients. The sera of patients were examined for IgG antibodies to HSV and VZV by the indirect immunoperoxidase technique. The geometric mean titer for VZV antibodies was significantly higher in the VZV-seropositive APFP patients than in the seropositive matched healthy control subjects. Nine APFP patients had increased or fourfold-rising VZV antibody titers on subsequent examinations, although six of them had presented without any evidence of zosterian eruption. The proportion of APFP patients with HSV antibodies at the time of admission was significantly higher than that of matched control subjects. No significant difference was found in the geometric mean titer for HSV antibodies between seropositive APFP patients and the seropositive control subjects. Only one patient in the series showed a fourfold rise in HSV antibodies, although the clinical symptomatology was compatible with this infection in 17 patients. The significance of serologic studies in determining the etiology of APFP is discussed. PMID- 6252120 TI - Energy spectra of delta-rays produced due to high energy particles with biological systems. PMID- 6252121 TI - Specific activity of uranium and thorium in marketable rock phosphate as a function of particle size. PMID- 6252122 TI - Hemoglobin variants and methods used for their characterization during 7 years of screening at the Center for Disease Control. AB - During 7 years of screening for hemoglobin variants, over 75 rare variants have been characterized. Of these, 18 were described for the first time. This report presents tabulated data regarding the structural and functional defects that were observed, information on the ethnic origin, and other special properties exhibited by these variants. The strategy and procedures for characterizing these variants are also summarized. PMID- 6252123 TI - The organization of the gamma-delta-beta gene complex in normal and thalassemia cells. AB - Restriction enzyme digestion analysis and direct human globin gene cloning have permitted analysis of the physical arrangement of nucleotide sequences within and surrounding the human globin genes. With these methods it has been shown that the linear arrangement 5' to 3' of the globin genes is G gamma-A gamma-delta-beta. The G gamma and A gamma genes are separated by about 3.5 kilobases (kb), while the A gamma and delta genes are 15 kb apart, and the delta and beta 6.5 kb apart. Each of these genes contains a large intervening sequence (IVS) of approximately 1 kb in precisely the same position between condons 104 and 105. In addition, each of these genes has a small IVS between codons 30 and 31. In homozygous delta beta thalassemia DNA, there is deletion of all of the normal delta and beta gene fragments. However, a new fragment 4.2 kb in size containing the 5' end of the delta globin gene is retained. Retention of this fragment in delta beta thalassemia, but not in HPFH is consistent with a role for sequences in this region for limiting gamma globin gene expression. Studies to date suggest that the beta + and beta 0 thalassemias will be due to a heterogeneous group of DNA defects affecting either beta globin gene transcription or beta mRNA processing. In most cases of beta + and beta 0 thalassemia DNA analyzed, there is no detectable deletion of beta or delta genes. In three India beta 0 patients, deletion of the 3' end of the beta gene has been found. Analysis of cloned beta globin genes from a patient with beta + thalasseia shows differences from normal in the fragments generated by restriction enzymes which cut frequently. Whether these differences are responsible for the defect in thalassemia or are polymorphisms unrelated to thalassemia remains to be determined. PMID- 6252124 TI - Diagnosis of Hb M disease by electron paramagnetic resonance spectra. PMID- 6252125 TI - The use of carcinoembryonic antigen and peptide hormones to stage and monitor patients with lung cancer. PMID- 6252126 TI - Immunologic monitoring of patients with small cell anaplastic carcinoma who are treated with chemotherapy and radiotherapy. PMID- 6252127 TI - Chemotherapy of inoperable lung cancer. PMID- 6252128 TI - Treatment of small cell lung cancer: progress, potential and problems. PMID- 6252129 TI - A randomized study: small cell anaplastic lung cancer treated by combination chemotherapy and adjuvant radiotherapy. PMID- 6252130 TI - Intensive induction chemotherapy of extensive small cell bronchogenic carcinoma in protected environment--prophylactic antibiotic units. A preliminary report. PMID- 6252131 TI - Half-body and local chest irradiation as consolidation following response to standard induction chemotherapy for disseminated small cell lung cancer: an Eastern Cooperative Oncology Group pilot report. PMID- 6252132 TI - "The state of the art" toward defining the role of radiation therapy in the management of small cell bronchogenic carcinoma. PMID- 6252133 TI - Small cell lung cancer: restrained optimism. PMID- 6252134 TI - A randomized study of split-course radiotheray of lung cancer: long term results. PMID- 6252135 TI - Action of streptothricin F on ribosomal functions. AB - The effect of streptothricin F on elongation factor-dependent and on elongation factor-free translation systems was studied. Streptothricin F inhibits factor dependent as well as factor-free polypeptide synthesis. The results suggest that streptothricin F inhibits polypeptide synthesis via interaction with the ribosome. In partial reactions streptothricin F impairs EF-G-dependent translocation and to a lesser extent EF-Tu-dependent binding of aa-RNA to the ribosome, while it does not affect peptide bond formation significantly. PMID- 6252136 TI - Synthesis of novel aminoglycoside antibiotics by periodic acid oxidation of neamine. PMID- 6252137 TI - Cefotaxime: a new cephalosporin antibiotic. PMID- 6252138 TI - Pharmacokinetics of cefotaxime in subjects with normal and impaired renal function. PMID- 6252139 TI - Pharmacokinetics of cefotaxime in neonates and children: clinical aspects. PMID- 6252140 TI - Cefotaxime concentration in cerebrospinal fluid. PMID- 6252141 TI - Cefotaxime concentrations in ascites. PMID- 6252142 TI - Concentrations of cefotaxime in bronchial secretions. PMID- 6252143 TI - Cefotaxime concentration in the bile and wall of the gallbladder. PMID- 6252144 TI - beta-Lactamase stability of cefotaxime. PMID- 6252145 TI - Cefotaxime concentrations in otitis media effusions. PMID- 6252146 TI - Determination of cefotaxime concentrations in non-infected human bone [proceedings]. PMID- 6252147 TI - Transfer of cefotaxime in human milk and from mother to foetus. PMID- 6252148 TI - Concentrations of cefotaxime in the anterior chamber of the eye in rabbits and humans. PMID- 6252149 TI - Clinical pharmacology of cefotaxime including penetration into bile, sputum, bone and cerebrospinal fluid. PMID- 6252150 TI - Allergic and immunological aspects of therapy with cefotaxime and other cephalosporins. PMID- 6252151 TI - Cefotaxime in lower respiratory tract infections compared to cefazolin. PMID- 6252153 TI - Cefotaxime in the treatment of lower respiratory tract infections. PMID- 6252152 TI - Cefotaxime in the treatment of pneumococcal pneumonia. PMID- 6252154 TI - Treatment of acute exacerbations of chronic bronchitis with cefotaxime: a controlled clinical trial. PMID- 6252155 TI - Some bacterial proteins with affinity for cefotaxime. PMID- 6252156 TI - Cefotaxime in bronchopulmonary infections--a clinical and pharmacological study. PMID- 6252157 TI - Cefotaxime for urinary tract infections. PMID- 6252158 TI - Cefotaxime in urinary tract infections--comparative clinical studies with gentamicin and with cefoxitin. PMID- 6252159 TI - Comparative studies of cefotaxime and sulbenicillin in complicated urinary tract infections. PMID- 6252160 TI - Elimination kinetics of cefotaxime in patients with renal insufficiency requiring dialysis. PMID- 6252161 TI - Cefotaxime therapy of urinary tract infections. PMID- 6252162 TI - A double blind clinical trial of cefotaxime and cefazolin in complicated urinary tract infections. PMID- 6252163 TI - Cefotaxime in children: efficacy, tolerance and effect on the intestinal bacterial flora. PMID- 6252164 TI - Cefotaxime in the treatment of severe paediatric infections. PMID- 6252165 TI - Cefotaxime therapy in children with serious infections associated with reduced host defense mechanisms. PMID- 6252166 TI - Antibacterial activity of cefotaxime and other newer cephalosporins (in vitro and in vivo). PMID- 6252167 TI - Evaluation of cefotaxime in a hospital with high antibiotic resistance rates. PMID- 6252168 TI - Cefotaxime in the treatment of septicaemia and endocarditis. PMID- 6252169 TI - Management of severe systemic infections caused by multiple resistant organisms. PMID- 6252170 TI - The treatment of bone and joint infections with cefotaxime. PMID- 6252171 TI - Cefotaxime in septicaemia including typhoid fever. PMID- 6252172 TI - Study of cefotaxime in the treatment of obstetric and gynaecological infections. PMID- 6252173 TI - Treatment of gonococcal urethritis in males with a single dose of cefotaxime [proceedings]. PMID- 6252174 TI - The treatment of gonococcal urethritis with cefotaxime [proceedings]. PMID- 6252175 TI - The evaluation of efficacy and safety of cefotaxime: a review of 2500 cases. PMID- 6252176 TI - Sensitivity testing and synergy. PMID- 6252177 TI - Antibacterial activity of cefotaxime. PMID- 6252178 TI - In vitro activity of cefotaxime and other cephalosporins against Neisseria gonorrhoeae. PMID- 6252179 TI - In vitro and in vivo activity of cefotaxime on gonococcal strains. PMID- 6252180 TI - Cefotaxime and amikacin: results of in vitro and in vivo studies against Gram negative bacteria and Staphylococcus aureus. EORTC International Antimicrobial Therapy Project Group. PMID- 6252181 TI - Chemistry of cefotaxime. PMID- 6252182 TI - Metabolism of cefotaxime in animals and man. PMID- 6252183 TI - Toxicology of cefotaxime in comparison to other cephalosporins. PMID- 6252184 TI - Pharmacokinetics of cefotaxime in normal human volunteers. PMID- 6252185 TI - Human metabolism of cefotaxime. PMID- 6252186 TI - Biochemical characterization of a fructokinase mutant of Rhizobium meliloti. AB - A double mutant strain (UR3) of Rhizobium meliloti L5-30 was isolated from a phosphoglucose isomerase mutant (UR1) on the basis of its resistance to fructose inhibition when grown on fructose-rich medium. UR3 lacked both phosphoglucose isomerase and fructokinase activity. A mutant strain (UR4) lacking only the fructokinase activity was derived from UR3; it grew on the same carbon sources as the parent strain, but not on fructose, mannitol, or sorbitol. A spontaneous revertant (UR5) of normal growth phenotype contained fructokinase activity. A fructose transport system was found in L5-30, UR4, and UR5 grown in arabinose fructose minimal medium. No fructose uptake activity was detected when L5-30 and UR5 were grown on arabinose minimal medium, but this activity was present in strain UR4. Free fructose was concentrated intracellularly by UR4 > 200-fold above the external level. A partial transformation of fructose into mannitol and sorbitol was detected by enzymatic analysis of the uptake products. Polyol dehydrogenase activity was detected in UR4 grown in arabinose-fructose minimal medium. The induction pattern of polyol dehydrogenase activities in this strain might be due to slight intracellular fructose accumulation. PMID- 6252187 TI - Insertion element IS102 resides in plasmid pSC101. AB - In vivo recombination was found to occur between plasmid pHS1, a temperature sensitive replication mutant of pSC101 carrying tetracycline resistance, and plasmid ColE1 after selection for tetracycline resistance at the restrictive temperature, 42 degrees C. Extensive analysis of the physical structures of three of these recombinant plasmids, using restriction endonucleases and the electron microscope heteroduplex method, revealed that the plasmid pHS1 was integrated into different sites on ColE1. The recombinant plasmids contained a duplication of a unique 1-kilobase (kb) sequence of pHS1 in a direct orientation at the junctions between the two parental plasmid sequences. This was confirmed by comparing the nucleotide sequence of the recombinants and their parental plasmids. Nucleotide sequence analysis further revealed that nine nucleotides at the site of recombination of ColE1 were duplicated at the junction of each of the 1-kb sequences. The formation of recombinants was independent of RecA function. Based on our previous finding that a plasmid containing a deoxyribonucleic acid insertion (IS) element can recombine with a second plasmid to generate a duplication of the IS element, we conclude that the 1-kb sequence is an insertion sequence, which we named IS102. For convenience, we have also denoted the IS102 sequence as eta theta to assign the orientation of the sequence. Eighteen nucleotides at one end (eta end) were found to be repeated in an inverted orientation at the other end (theta end) of IS102. The nucleotide sequence of the eta end of the sequence was found to be identical to the sequence at the ends of the transposon Tn903, which is responsible for transposition of the kanamycin resistance gene. PMID- 6252189 TI - Synchronization of cell division in microorganisms by percoll gradients. AB - We describe a method for obtaining synchronously dividing cells of bacteria (Escherichia coli B and K-12 and Bacillus subtilis 168) and fission yeasts (Schizosaccharomyces pombe) by the use of Percoll density gradients. PMID- 6252188 TI - Regulation of enzyme synthesis in the arginine deiminase pathway of Pseudomonas aeruginosa. AB - The three enzymes of the arginine deiminase pathway in Pseudomonas aeruginosa strain PAO were induced strongly (50- to 100-fold) by a shift from aerobic growth conditions to very low oxygen tension. Arginine in the culture medium was not essential for induction, but increased the maximum enzyme levels twofold. The induction of the three enzymes arginine deiminase (EC 3.5.3.6), catabolic ornithine carbamoyltransferase (EC 2.1.3.3), and carbamate kinase (EC 2.7.2.3) appeared to be coordinate. Catabolic ornithine carbamoyltransferase was studied in most detail. Nitrate and nitrite, which can replace oxygen as terminal electron acceptors in P. aeruginosa, partially prevented enzyme induction by low oxygen tension in the wild-type strain, but not in nar (nitrate reductase negative) mutants. Glucose was found to exert catabolite repression of the deiminase pathway. Generally, conditions of stress, such as depletion of the carbon and energy source or the phosphate source, resulted in induced synthesis of catabolic ornithine carbamoyltransferase. The induction of the deiminase pathway is thought to mobilize intra- and extracellular reserves of arginine, which is used as a source of adenosine 5'-triphosphate in the absence of respiration. PMID- 6252190 TI - Salmonella typhimurium mutants with reduced levels of transfer ribonucleic acid inhibitable endodeoxyribonucleolytic activity. AB - Two methods of mutagenesis, chemical alkylation and insertion of the tetracycline resistance transposon Tn10, were used to generate mutants of Salmonella typhimurium which had reduced levels of endodeoxyribonucleolytic activity. The chemically induced mutations defined a locus, endA, which was cotransduced with serA at a low frequency and with metK at a high frequency. Three-factor crosses revealed that metK was between serA and endA. The major endodeoxyribonucleolytic activity in crude extracts of s. typhimurium was similar to the activity of Escherichia coli endonuclease I. A Tn10 insertion mutation of endA resulted in the most severe loss of endodeoxyribonucleolytic activity among the endA alleles studied. Two of the chemically induced mutations resulted in activities which were more thermolabile than the wild-type activity. PMID- 6252191 TI - Suppression of defects in cyclic adenosine 3',5'-monophosphate metabolism in Escherichia coli. AB - Strain MM6-13 (ptsI suc lacI sup) of Escherichia coli contains a suppressor of the succinate-negative phenotype. In MM6-13, sup caused enhanced growth in glycerol, maltose, melibiose, and succinate media and increased activity of beta galactosidase and tryptophanase relative to an isogenic strain without sup. In strain A61 (cya sup), sup partially suppressed cya. Cyclic guanosine monophosphate increased beta-galactosidase activity sevenfold in A61 and enabled this strain to grow on maltose, galactose, succinate, and arabinose. Strain A61 responded to much lower concentrations of cyclic adenosine monophosphate than cyclic guanosine monophosphate. It appears that sup is located in the crp locus. These results suggest that sup mutants have an altered cyclic adenosine monophosphate receptor protein which is activated by cyclic guanosine monophosphate and has an increased affinity for cyclic adenosine monophosphate. PMID- 6252192 TI - Physical and functional mapping of RP4-TOL plasmid recombinants: analysis of insertion and deletion mutants. AB - Cleavage sites for the restriction endonucleases XhoI, BamHI, HindIII, and EcoRI were mapped on the pTN2 plasmid, a recombinant of TOL and RP4, which specifies the toluene-degrading enzymes in the same way as the wild-type TOL plasmid. The pTN2 plasmid, purified from a strain of Escherichia coli, contained the entire length of the RP4 plasmid (about 54 kilobase pairs [kb]) and the TOL segment (about 56 kb). The TOL segment is inserted at about 12 and 5 kb away from the EcoRI and BamHI cleavage sites of RP4, respectively. Cleavage sites for XhoI, BamHI, HindIII, and EcoRI were also mapped on an insertion mutant, pTN1, and two deletion mutants, pTN81 and pTN9. Analysis of pTN81 and pTN9 allowed estimation of the region of the gene cluster for benzyl alcohol dehydrogenase and benzaldehyde dehydrogenase, as well as the region required for toluate oxygenase activity. Induction of TOL enzymes directed by pTN1 suggested the location and orientation of transcription of the gene cluster for catechol 2,3-oxygenase, 2 hydroxymuconic semialdehyde dehydrogenase, and 2-hydroxymuconic semialdehyde hydrolase. Analysis of strains carrying both pTN9 and a xylR mutant of the TOL plasmid demonstrated that xylR+ is trans dominant over xylR. PMID- 6252193 TI - Regulation of ilvEDA expression occurs upstream of ilvG in Escherichia coli: additional evidence for an ilvGEDA operon. AB - A low-copy-number plasmid was prepared that contained the entire ilv gene cluster of Escherichia coli. The introduction of an ilvO mutation allowed the ilvG gene of the plasmid to be expressed and imparted valine resistance to strains carrying it. Insertion of Tn10 into the ilvG gene of the plasmid resulted in a strong polar effect on ilv genes E, D, and A. Replacement of a region of ilv deoxyribonucleic acid between two KpnI sites on the high-copy-number plasmid carrying the entire ilv gene cluster with a KpnI fragment carrying an ilv-lac fusion but not extending into the ilv-specific control region resulted in a plasmid expressing the lacZ gene under ilv control when the fusion had been inserted in its normal orientation but not when it had been inserted in the opposite orientation. These experiments indicate that ilv-specific control over ilvE, ilvD, and ilvA expression is dependent on these genes being continguous with deoxyribonucleic acid that lies upstream of ilvG. The results also add further support to the concept of an ilvGEDA operon in E. coli. PMID- 6252194 TI - Clostridium perfringens type A: in vitro system for sporulation and enterotoxin synthesis. AB - Polysomes were isolated from an enterotoxigenic strain of Clostridium perfringens during vegetative growth and at 1-h intervals after transfer into Duncan-Strong sporulation medium. During vegetative growth, about 67% of the ribosomes were in polysomal complexes. This proportion decreased to about 20% during the first 2 h in sporulation medium and then gradually increased to a maximum of 45% at 6 h. Ribosomes isolated from cells in vegetative or in sporulation phase could equally translate vegetative, sporulation, and natural viral R17 messenger ribonucleic acid with either vegetative or sporulation initiation factors. When polysomes were allowed to complete their nascent chains with labeled amino acids in vitro, most of the polypeptides synthesized by the vegetative phase and by the sporulation phase polysomes appeared to be identical. There were, however, notable differences upon further investigation. Specifically, when antiserum against the enterotoxin was reacted with the completed polypeptides, no counts were precipitated from the vegetative products. On the other hand, up to 12% of the total labeled protein was precipitated from the products obtained with the sporulation phase polysomes. Upon electrophoresis on sodium dodecyl sulfate, the putative enterotoxin synthesized in vitro ran as a major band with a molecular weight of 35,000, and as two minor bands with molecular weights of 17,000 and 52,000, respectively. PMID- 6252195 TI - Morphogenetic effects of light and guanine derivatives on the fruiting myxobacterium Stigmatella aurantiaca. AB - When low cell densities of the myxobacterium Stigmatella aurantiaca were starved on an inorganic salts and agar medium, cell aggregation and fruiting body formation showed a striking dependency upon the presence of light. This dependency was not manifested when sufficient amounts of guanosine or guanine nucleotides were added to the medium. Light interacted cooperatively with suboptimal concentrations of guanine compounds to promote development. None of the other purine or pyrimidine derivatives, with the exception of adenine, stimulated development. However, aggregates that formed in the presence of adenine did not mature into fruiting bodies and instead disaggregated. PMID- 6252196 TI - Identification of a second tetracycline-inducible polypeptide encoded by Tn10. AB - Three Tn10 polypeptides were detected by analyzing the proteins synthesized in ultraviolet light-irradiated Escherichia coli cells after infection with lambda::Tn10. One of these polypeptides was the previously identified 36,000 dalton TET polypeptide. The other two had approximate sizes of 25,000 and 13,000 daltons. The syntheses of both the TET polypeptide and the 25,000-dalton polypeptide were inducible by tetracycline in lambda-immune hosts. Similarly, the synthesis of the TET polypeptide was inducible in nonimmune hosts. However, the synthesis of the 25,000-dalton polypeptide was constitutive in nonimmune hosts. An amber mutation in a gene required for tetracycline resistance on lambda::Tn10 was isolated that eliminated the synthesis of the TET polypeptide in sup+ hosts but not the synthesis of the 25,000-dalton or the 13,000-dalton polypeptides. The expression of tetracycline resistance from wild-type Tn10 was found to be anomalous in E. coli strains carrying the amber suppressors supD, supE, and supF. In general, strains containing these nonsense suppressors were less resistant to tetracycline. PMID- 6252197 TI - Partial purification and characterization of an exonuclease from Xanthomonas oryzae. AB - An exonuclease with a strong preference for single-stranded deoxyribonucleic acid over double-stranded deoxyribonucleic acid has been purified 500-fold from Xanthomonas oryzae. This enzyme liberates 5'-mononucleotides in a reaction which requires Mg2+. PMID- 6252198 TI - Characterization of Tn904 insertions in octopine Ti plasmid mutants of Agrobacterium tumefaciens. AB - Seven Tn904 insertion mutants of pTi Ach5 affecting Agrobacterium tumefaciens virulence were studied. The mutant character was shown to be plasmid borne. Four of these mutants were avirulent and carried an insertion in restriction endonuclease HpaI fragment 12, a 3.3-megadalton fragment, which therefore appears to be a Ti plasmid region essential for virulence. Two mutants were attenuated in virulence. The inserts mapped close to HpaI fragment 12. One mutant giving rise to small tumors with excessive adventitious root formation on Kalanchoe daigremontiana carried an insertion in the right side of the common sequence in the deoxyribonucleic acid of the Ti plasmid detected in crown gall tumors. The insertion behavior of Tn904 was studied by analyzing 11 independently isolated and randomly chosen mutants. The Tn904 inserts did not affect oncogenicity, tumor morphology, bacterial transfer functions, octopine catabolism functions, or vital parts of the Ti plasmid, such as the origin of replication. Most of the Tn904 inserts were concentrated in a small part of the map. The size of additional deoxyribonucleic acid as a result of Tn904 inserts varied between 5 and 15 megadaltons. In two cases a Ti plasmid was found with two Tn904 insertions at different positions. PMID- 6252199 TI - Purification and characterization of cytochrome P-450 with high affinity for cytochrome b5. PMID- 6252200 TI - Purification and characterization of a poly(A) polymerase from beef liver nuclei. AB - Poly(A) polymerase [EC 2.7.7.19] was highly purified from beef liver nuclei by the use of column chromatographies on heparin-Sepharose 4B and Blue Dextran Sepharose 4B. The purified enzyme showed one major protein band of the molecular weight of 57,000 in SDS polyacrylamide gel electrophoresis, which agreed with the molecular weight estimated from glycerol gradient centrifugation. The enzyme required the presence of Mn2+ for its activity but was almost completely inactive with Mg2+. It incorporated specifically ATP into polynucleotide as a sole substrate. The enzyme activity dependend entirely on the addition of exogenous polynucleotide primer. It showed certain selectivity for the primers. The most effective among the tested polynucleotides was a short poly(A), for which the Km of the enzyme was shown to be 7 microM. Poly(G, U) and short poly(U) also primed the reaction, but tRNA, phage RNA, poly(G), and poly(C) were inactive. Based on observed specificity for the primer, the role of this enzyme in the cell nuclei was discussed. Digestion of the reaction product of this enzyme by two specific exonucleases, snake venom and spleen phosphodiesterases, suggested that this enzyme catalyzed the covalent bonding of the substrate to the 3' terminus of the primer as in the manner expected for in vivo polyadenylation. PMID- 6252201 TI - Multiple forms of cytochrome P-450 purified from liver microsomes of phenobarbital- and 3-methylcholanthrene-pretreated rabbits. II. Spectral properties. AB - The spectral properties of multiple forms of cytochrome P-450 purified or partially purified from liver microsomes of phenobarbital (PB)- and 3 methylcholanthrene (MC)-treated rabbits have been studied. Both optical absorption and EPR studies have shown that the oxidized forms of P-450(1), P 450(2) (from PB-treated animals), and P-450(3) (from MC-treated animals) are in the low spin state, having a Soret absorption peak at 417-418 nm. Oxidized P 448(1) (from both PB- and MC-treated animals), on the other hand, shows a Soret peak at 393 nm and a weak band at 646 nm. This and EPR evidence indicate that P 448(1) contains heme which is predominantly in the high spin state, though EPR studies at low temperature indicate the presence of a small amount of low spin ferric heme. The presence of tightly bound MC in P-448(1) purified from MM treated animals is reflected by characteristic absorption peaks in the ultraviolet region, but this does not affect the absorption spectra in the Soret and visible regions. Emulgen 913, a nonionic detergent, causes the conversion of oxidized P-448(1) from the high to the low spin state, as evidenced by optical absorption and EPR results; bound MC inhibits this conversion in a noncompetitive way. Binding of ethyl isocyanide to reduced P-450(1) and P-448(1) results in the appearance of two Soret peaks in the 430 and 455 nm regions, the relative intensities of which are dependent on pH. At any pH the 455 nm peak of P-448(1) is always higher than that of P-450(1). Benzphetamine and aniline, added to oxidized P-450(1), cause Type I and Type II spectral changes, respectively, but the magnitudes of the changes are small in both cases. The Soret peak of oxidized P-448(1) at 393 nm is completely shifted to 420 nm on addition of aniline, resulting in a reverse Type I spectral change; acetanilide causes the conversion of the Soret peak to the low spin state to only a slight extent. The conversions caused by aniline and acetanilide are both inhibited by the presence of tightly bound MC. On the basis of these and other observations, the spin state of these P 450's are discussed. PMID- 6252202 TI - Structural difference between larval and adult cytochromes c of the horsefly, Musca domestica. AB - The structural difference between larval and adult cytochromes c of the housefly, Musca domestica was studied. The two cytochromes differed in electrophoretic behavior and amino acid composition from each other. Peptide maps prepared from the tryptic digests of the two cytochromes were also different from each other in several regions. Amino acid analyses of the peptides separated on the maps showed that the primary structure differed between the two cytochromes in at least 5 positions. PMID- 6252204 TI - Recovery of quenched radioactivity from thin-layer chromatographic plates. An improved assay for cGMP phosphodiesterase in Myxococcus xanthus. AB - Ammonium bicarbonate was found useful in extracting a variety of radiolabeled compounds from thin-layer chromatographic plates. The technique significantly increased the sensitivity of the assay for cyclic nucleotide phosphodiesterases. This method was used to show unequivocally, the presence of cGMP phosphodiesterase in vegetative cells of Myxococcus xanthus. PMID- 6252203 TI - ATP dependent reversible conformational change of Na+,K+-ATPase modified with N (p-(2-benzimidazoly)phenyl)maleimide. AB - Na+,K+-ATPase [EC 3.6.1.3] from pig kidneys was treated with the fluorescent reagent N-(p-(2-benzimidazolyl)phenyl)maleimide (BIPM) in the presence of CKl. The resultant preparation showed 70% of the activity with only a small change in the apparent affinity for ligands of the enzyme. The addition of Na+ to the treated preparation induced a -2.1 +/- 0.1% change of the total fluorescence intensity observed in the absence of Na+. Further addition of both Mg2+ and ATP transiently increased the fluorescence to +0.5 +/- 0.1%. After the exhaustion of ATP, the fluorescence decreased to -3.1 +/- 0.1%. This cycle can be repeated by the readdition of ATP but not by ADP. Ouabain inhibits the fluorescence change. The ligands used reduced the fluorescence intensity as follows: Mg2+ + Na+ + ATP approximately K+, none, Mg2+ approximately ATP, Na+ + ATP, Na+ approximately Na+ + Mg2+, Na+ + Mg2+ + ADP approximately Na+ + ADP. The data indicate the presence of multiple conformational states of the enzyme. PMID- 6252205 TI - Purification of rat liver glycerate kinase and studies of its enzymatic and immunological properties. AB - Glycerate kinase was purified to near homogeneity from rat liver mitochondria. Sephadex G-100 chromatography and sodium dodecyl sulfate-gel electrophoresis showed that the enzyme is a monomer with a molecular weight of 51,000-56,000. Kinetic studies indicated that the reaction proceeds by the "rapid equilibrium random sequential" mechanism, and the Michaelis constants were found to be 0.032 mM and 0.091 mM for D-glycerate and ATP, respectively. The binding of D-glycerate specifically protected the enzyme from thermal inactivation. The dissociation constant of the enzyme.D-glycerate complex was similar to the Michaelis constant, suggesting that the protective effect of D-glycerate may be caused by the specific binding of the substrate to the active site of the enzyme. The antibody to the enzyme was prepared by immunizing a rabbit with the purified rat liver glycerate kinase. Immunological experiments indicated that the cytosol and mitochondrial enzymes are indistinguishable. It was also found by immunological studies that the increase in the cytosol and mitochondrial enzyme activity depending on dietary protein intake was proportional to the increase in enzyme protein. These results support our proposal (Kitagawa, Y., Katayama, H., & Sugimoto, E. (1979) Biochim. Biophys. Acta 582, 260-275) that cytosol and mitochondrial glycerate kinase arise from a common translation product and that dietary protein regulates the distribution of glycerate kinase to the cytosol and mitochondria. PMID- 6252206 TI - Affinity chromatography of porcine pancreas deoxyribonuclease I on DNA-binding sepharose under non-digestive conditions, using its substrate-binding site. AB - 1. DNase I from porcine pancreas, if Mg2+ was present, hydrolyzed both sDNA and dDNA, whether free or bound to Sepharose. The hydrolysis rates were maximum at pH 7.5 with the bound DNAs and at pH 7.0 with the free DNAs negligible at pH 4.0 and pH 10.5 with the free and bound DNAs. The hydrolysis was completely inhibited by 50 mM sodium citrate. 2. With 50 mM citrate buffer (Ph 4.0), DNase I was effectively adsorbed on the DNA-Sepharoses in the absence of 5 mM Mg2+. The adsorbed enzyme was effectively eluated by the buffer containing 1 M KCl (eluate). The amounts of the eluated enzyme were approximately 1.5 X 10(5) units/mg DNA with sDNA-Sepharose and approximately 3.0 X 10(5) units/mg DNA with dDNA-Sepharose. This simple adsorption-elution of the pancreas extract resulted in approximately 300-fold purification of DNase I with a yield of 95%. In the elute, the ratios in activity of trypsin, chymotrypsin and RNase to DNase I were 1/(4.0 X 10(5)), 1/(5.3 X 10(3)), and 1/(4.1 X 10(2)) as low as in the extract, respectively. In addition, the eluate was not contaminated by kallikrein or carboxypeptidases A and B. 3. Upon repeating the adsorption-elution described above, the adsorbing capacities of DNA-Sepharoses gradually deteriorated with the whole pancreas extract, but not with the precipitate of the extract formed on 60% ammonium sulfate saturation, which contained 90% of the DNase I. With the precipitate, one dDNA-Sepharose solumn was repeatedly usable at least 20-times without deterioration. The DNase I preparation thus obtained was homogeneous on SDS-polyacrylamide gel electrophoresis. 4. Conceivably, the above-mentioned adsorption of DNase I on DNA-Sepharoses was mainly due to the steric and electrostatic affinity of a relatively large moiety of the DNA molecule to the substrate-binding site, but not to the catalytic site, of the enzyme. PMID- 6252207 TI - P1,P5-Di(adenosine-5')pentaphosphate(Ap5A) as an inhibitor of adenylate kinase in studies of fragmented sarcoplasmic reticulum from bullfrog skeletal muscle. AB - We examined the effects of P1,P5-di(adenosine-5')pentaphosphate (Ap5A), a potent inhibitor of adenylate kinase, on fragmented sarcoplasmic reticulum (FSR) obtained from bullfrog skeletal muscle in view of the possible usefulness of the nucleotide in experiments with FSR to avoid complications due to contaminating adenylate kinase. Ap5A itself does not cause Ca uptake in the place of ATP. It inhibited adenylate kinase activity without affecting the Ca-ATPase or Ca uptake activity of FSR. The observed effect was a competitive inhibition of basic ATPase activity of the light fraction of FSR. Therefore, P1,P5-di(adenosine 5')pentaphosphate represents an extremely useful tool in experiments wth fragmented sarcoplasmic reticulum, such as studies of H+ movement accompanying Ca movement, ATP-ADP exchange reaction, and calorimetry of the Ca uptake process. A rather high concentration (50 muM or more) of Ap5A is required for complete inhibition of adenylate kinase. Further, we detected 1.3-2.8 nmol of (ATP + ADP), 2-4 nmol of Pi, and unidentified metal(s) in 50 nmol of Ap5A, and Ap5A is more labile to acid and molybdate than ATP. PMID- 6252208 TI - Study of surface charge of the intima and artificial materials in relation to thrombogenicity. PMID- 6252209 TI - Biliary stricture dilatation: use of the Gruntzig balloon catheter. AB - The Grunzig ballon catheter in use for angioplasty was found well suited for the dilatation of strictures in the biliary tract. It may be applied in benign or malignant strictures or for dilatation of the T-tube sinus tract. The application of the ballon catheter is described for malignant stricture dilatation preceding internal biliary drainage procedures. PMID- 6252210 TI - Inhibition of DNA synthesis in adrenocortical cells by cytochalasin B. AB - ACTH inhibits DNA synthesis in normal rat and mouse tumor Y-1 adrenocortical cells within the same concentration range that it stimulates steroidogenesis. These processes can be independently regulated as demonstrated by the divergent actions of cytochalasin B on these cells. In the normal cells, cytochalasin B does not increase steroidogenesis in serum-free or serum-containing media, and it decreases the stimulation produced by ACTH. In the absence of serum, the Y-1 cells respond in a similar way. However, in serum-containing media, cytochalasin B increases steroidogenesis in these cells and does not inhibit the response to ACTH. In both cell types, cytochalasin B inhibits [3H]thymidine incorporation into DNA by a mechanism different than that of ACTH. In the Y-1 cells, this inhibition is caused by a decreased uptake of [3H]thymidine into the cell, which probably reflects a decreased transport across the cell membrane. In the normal cells, cytochalasin B, like ACTH, does not affect [3H]thymidine transport, but it decreases DNA synthesis much more rapidly than does ACTH. This inhibition may be the result of the disruption of microfilaments by cytochalasinB, because our evidence indicates that it is not caused by a decrease in glucose uptake by the cells. PMID- 6252211 TI - Transport of the membrane glycoprotein of vesicular stomatitis virus to the cell surface in two stages by clathrin-coated vesicles. AB - The G protein of vesicular stomatitis virus is a transmembrane glycoprotein that is transported from its site of synthesis in the rough endoplasmic reticulum to the plasma membrane via the Golgi apparatus. Pulse-chase experiments suggest that G is transported to the cell surface in two successive waves of clathrin-coated vesicles. The oligosaccharides of G protein carried in the early wave are of the "high-mannose" (G1) form, whereas the oligosaccharides in the second, later wave are of the mature "complex" (G2) form. the early wave is therefore proposed to correspond to transport of G in coated vesicles from the endoplasmic reticulum to the Golgi apparatus, and the succeeding wave to transport from the Golgi apparatus to the plasma membrane. The G1- and G2-containing coated vesicles appear to be structurally distinct, as judged by their differential precipitation by anticoated vesicle serum. PMID- 6252212 TI - Coalescence of microsomal vesicles from rat liver: a phenomenon occurring in parallel with enhancement of the glycosylation activity during incubation of stripped rough microsomes with GTP. AB - Rough microsomes from rat liver have been subjected to various treatments and incubated afterwards with UDP-N-acetyl-[14C]glucosamine and GDP-mannose in the presence of GTP (0.5 mM), or of other nucleotides. In agreement with earlier results from this laboratory, the preparations previously treated to strip off the ribosomes and incubated in the presence of GTP assembled dolichol-linked oligosaccharides and transferred these oligosaccharides to endogenous protein acceptors much more actively than untreated preparations, or stripped preparations incubated in the absence of GTP. Thin-section and freeze-fracture electron microscopy have revealed that pyrophosphate-treated preparations incubated with GTP are aggregated and contain numerous vesicles as large as 1-4 micrometer, or more. Such large vesicles were not present before incubation and thus were considered to have been formed through coalescence of regular-sized ones. Like glycosylation, the coalescence phenomenon depends upon the removal of ribosomes, because it occurred whether ribosomes had been stripped, at least partly, with pyrophosphate, KCl, or puromycin, but not when rough microsomes had been washed with 0.25 M sucrose or with KCl and MgCl2. Like glycosylation, it also depends on the addition of GTP and was not induced by ATP, UTP, CTP, and nonhydrolysable analogues of GTP. Rough microsomes coalesced, however, when pyrophosphate-treated preparations were incubated with GTP in the absence of nucleotide sugars, or in the presence f tunicamycin, indicating that the coalescence phenomenon does not result from the glycosylation of some membrane constituents. PMID- 6252213 TI - Three-dimensional crystals of an integral membrane protein: an initial x-ray analysis. AB - Matrix protein, a pore-forming transmembrane protein spanning the outer membrane of Escherichia coli, has been obtained in a variety of three-dimensional crystal forms amenable to both electron microscope and x-ray analyses. Successful association into large crystals depended on the use of alpha-octyl glucoside, a detergent with relatively low affinity for the protein. Electron micrographs of thin-sectioned crystals show a high degree of order. Preliminary crystallographic data suggest that the crystals, which exhibit diffraction to 3.8 A, have a cubic space group. PMID- 6252214 TI - Isolation and partial characterization of the plasma membrane of the sea urchin egg. AB - The cell surface complex (Detering et al., 1977, J. Cell Biol. 75, 899-914) of the sea urchin egg consists of two subcellular organelles: the plasma membrane, containing associated peripheral proteins and the vitelline layer, and the cortical vesicles. We have now developed a method of isolating the plasma membrane from this complex and have undertaken its biochemical characterization. Enzymatic assays of the cell surface complex revealed the presence of a plasma membrane marker enzyme, ouabain-sensitive Na+/K+ ATPase, as well as two cortical granule markers, proteoesterase and ovoperoxidase. After separation from the cortical vesicles and purification on a sucrose gradient, the purified plasma membranes are recovered as large sheets devoid of cortical vesicles. The purified plasma membranes are highly enriched in the Na+/K+ ATPase but contain only very low levels of the proteoesterase and ovoperoxidase. Ultrastructurally, the purified plasma membrane is characterized as large sheets containing a "fluffy" proteinaceous layer on the external surface, which probably represent peripheral proteins, including remnants of the vitelline layer. Extraction of these membranes with Kl removes these peripheral proteins and causes the membrane sheets to vesiculate. Polyacrylamide gel electrophoresis of the cell surface complex, plasma membranes, and Kl-extracted membranes indicates that the plasma membrane contains five to six major proteins species, as well as a large number of minor species, that are not extractable with Kl. The vitelline layer and other peripheral membrane components account for a large proportion of the membrane associated protein and are represented by at least six to seven polypeptide components. The phospholipid composition of the Kl-extracted membranes is unique, being very rich in phosphatidylethanolamine and phosphatidylinositol. Cholesterol was found to be a major component of the plasma membrane. Before Kl extraction, the purified plasma membranes retain the same species-specific sperm binding property that is found in the intact egg. This observation indicates that the sperm receptor mechanisms remain functional in the isolated, cortical vesicle free membrane preparation. PMID- 6252215 TI - Ca2+-dependent recycling of synaptic vesicles at the frog neuromuscular junction. AB - Frog cutaneous pectoris muscles were treated with low doses of crude black widow spider venom (BWSV) or purified alpha-latrotoxin, and neuromuscular transmission, quantal secretion, changes in ultrastructure and uptake of horseradish peroxidase (HRP) were studied. When these agents were applied to muscles bathed in a Ca2+ free solution with 1 mM EGTA and 4 mM Mg2+, the rate of quantal secretion rose to high levels but quickly subsided; neuromuscular transmission was totally and irreversibly blocked within 1 h. The terminals became swollen and were depleted of vesicles; HRP was not taken up. When BWSV was applied to other muscles bathed in a solution with 1.8 mM Ca2+ and 4 mM Mg2+, the rate of secretion rose to high levels and then declined to intermediate levels that were sustained throughot the hour of exposure. Neuromuscular transmission was blocked in fewer than 50% of these fibers. The ultrastructure of these terminals was normal and they contained large numbers of synaptic vesicles. If HRP had been present, most of the synaptic vesicles were labeled with reaction product. These observations suggest that Ca2+ plays an important role in endocytosis at the frog neuromuscular junction. PMID- 6252217 TI - Cyclic AMP levels in migrating and non-migrating newt epidermal cells. AB - Cyclic AMP (cAMP) levels were measured in 8-hour migrating wound epithelial and non-migrating epithelial cells of the newt. Tissues were collected in vivo and in vitro with and without epidermal-dermal separation by collagenase. Regardless of manner of collection and treatment, cAMP levels were always significantly higher in the migrating cells. Levels were also measured in 28-hour and 36-hour wound epithelia. There was a progressive decline in levels in wound epithelia between 8, 28, and 36 hours, suggesting that levels were in the process of returning to normal. When cells were treated with a dose of cAMP and theo-phylline previously shown to inhibit migration, levels of cAMP were much higher than any migrating epithelium. The fact that cAMP inhibits migration, yet migrating cells have higher cAMP levels, seems contradictory at first, but possible explanations are advanced to account for the apparent discrepancy. PMID- 6252216 TI - Regulated expression of the prolactin gene in rat pituitary tumor cells. AB - Prolactin (PRL) gene expression in three strains of GH cells (rat pituitary tumor cells) has been quantitated by measurement of: (a) intracellular and extracellular PRL, (b) cytoplasmic translatable PRL-specific mRNA (mRNAPRL), and (c) molecular hybridization of cytoplasmic poly(A) RNA to cDNAPRL (DNA complementary to mRNAPRL). Three GH cell lines utilized in this investigation were a PRL-producing (PRL+) strain, GH4C1, a PRL nonproducing 5-bromo deoxyuridine resistnat (PRL- BrdUrdr) strain, F1BGH12C1, and a new strain, 928 9b, derived by fusion of PRL+ cells with a nuclear monolayer of the PRL-, BrdUrdr GH cell strain. PRL production is a characteristic of 928-9b cells, but the level of PRL production (2-4 micrograms/mg protein/24 h) is much lower than that of the PRL+ strain, GH4C1 (15-25 micrograms/mg protein/24 h). Levels of cytoplasmic translatable mRNAPRL and cytoplasmic PRL-RNA sequences quantitated with a cDNAPRL probe were also much lower in 928-9b as compared to the PRL+ parent. PRL-RNA sequences could not be detected in the PRL- strain. Thyrotopin-releasing hormone (TRH) stimulates PRL synthesis about threefold and inhibit a growth hormone (GH) synthesis 72% in the PRL+ strain. TRH has no effect on the synthesis of either PRL or GH in the 928-9b strain, although TRH receptors could be detected in these cells. Stimulation of PRL synthesis in the PRL+ strain by TRH could be correlated with increases in levels of cytoplasmic translatable mRNAPRL and increases in cytoplasmic PRL-RNA sequences. These results demonstrate that the graded expression of the PRL gene at the basal level, and in response to TRH, is caused by the regulated production of specific mRNA, i.e., mRNAPRL in these three GH cell strains. PMID- 6252219 TI - Studies of membrane fusion. VI. Mechanism of the membrane fusion and cell swelling stages of Sendai virus-mediated cell fusion. AB - The membrane fusion and cell swelling stages of Sendai virus-mediated cell-cell fusion have been studied by thin-section and freeze-fracture electron microscopy. Sites of membrane fusion have been detected in human erythrocytes arrested at the membrane fusion stage of cell fusion and in virtually all cases a fused viral envelope or envelope components has been identified thus providing further direct evidence that cell-viral envelope-cell bridge formation is the membrane fusion event in Sendai virus-induced cell fusion. Radial expansion of a single virus bridge connecting 2 cells is sufficient to produce a fused cell. Membrane redistribution which occurs during this cell swelling stage of the fusion process is often accompanied by the formation of a system of membrane tubules in the plane of expansion of the virus bridge. The tubules originate from points of fusion between the bridging virus envelope and the erythrocyte membrane and also expand radially as cells swell. Ultimately membrane rupture occurs and the tubules appear to break down as small vesicles. When previously observed in cross sectioned cells these membrane tubules were interpreted as sites of direct membrane fusion. The present study indicates that this interpretation is incorrect and shows that the tubules are generated subsequent to membrane fusion when 2 cells connected by a virus bridge are induced to swell. A mechanism to explain the formation of this system of membrane tubules is proposed. PMID- 6252218 TI - Divergent effects of long acting cyclic nucleotides and lysine vasopressin on the release of matrix sulfated proteoglycans into the medium of fetal rat chondrocytes in monolayer culture. AB - Release of sulfated proteoglycans into the medium of fetal rat chondrocytes in monolayer culture was studied by contrasting the effects of 10% calf serum, long acting cyclic nucleotides (8 Br-cAMP or DBcAMP), and lysine vasopressin (LVP). Eight hours after initiation of the experiment, the monolayer was pulsed for 2 hours with Na2[35SO4=], the radioactivity was chased, and the monolayer was reincubated for 6 hours with conditioned medium from replicate cultures. Immediately after labelling, the amount of newly synthesized sulfated proteglycans was invariably higher in the insoluble matrix than in the medium compartment. Both additives selectively enhanced sulfate incorporation into chondroitin sulfate of the matrix when compared to serum controls, but only LVP stimulation caused increases in the medium. Remodeling (loss of cell layer and release into the medium at 6 hours) was suppressed by cAMP analogues and increased by LVP. This process was more active in cultures of lower cell density. Utilizing calibrated gel columns, no size difference of the glycosaminoglycans was found between the medium and cell layer compartments of the three treatment groups at the two time points. Because the cAMP analogues inhibit, while LVP stimulates cell division, our observations imply that the rate of degradation of the constraining matrix is increased when replication is favored, even when chondriotin sulfate synthesis is selectively stimulated. PMID- 6252220 TI - Aggregation properties of chondrocytes infected with a temperature-sensitive mutant of Rous sarcoma virus. AB - Aggregation capacity of chicken embryo chondrocytes decreases when transformed by Rous sarcoma viruses. Cell-to-cell aggregation capacity of chondrocytes infected with a T class temperature-sensitive mutant (tsNY68) (with the temperature sensitive lesion at the src gene) of Rous sarcoma virus is dependent upon the temperature at which these cells are grown. When grown at the permissive temperature (36 degrees C), where the transforming gene is expressed, aggregation capacity was lower than normal while infected cells grown at the non-permissive temperature (41.5 degrees C) had similar capacity to aggregate to that of normal chondrocytes. However, after a prolonged period of culture (10 days), chondrocytes transformed by wild type SR-RSV regained the normal level of aggregation capacity. Cells transformed by tsNY68 and incubated at the permissive temperature for 10 days also regained the normal level of aggregation capacity. It appears therefore that RSV-transformed chondrocytes first become less adhesive but during long-term cultivation they regain their property to aggregate. The decrease of aggregation capacity due to T class mutants of RSV at 36 degrees C is dependent on constant maintenance of protein synthesis because addition of cycloheximide restored the aggregation capacity even at the permissive temperature. PMID- 6252221 TI - Fusion of human erythrocytes induced by Sendai virus: freeze-fracture aspects. AB - Analysis of the freeze-fracture morphology of human erythrocytes during Sendai virus-induced fusion indicates that it occurs in several spots, with the formation of membrane-bound cytoplasmic connexions. Radial expansion of these connexions causes the formation of a polymorphic network of membrane tubules with a lumen continuous with the external space. Our results are best explained assuming that the viral envelopes do not necessarily participate directly in inter-membrane fusion but, instead, indirectly through conditioning and modification of the erythrocyte membranes by viral membrane components. PMID- 6252222 TI - An unusual form of vitamin D-dependent rickets in a child: alopecia and marked end-organ hyposensitivity to biologically active vitamin D. AB - A 12-yr-old female patient with an unusual form of vitamin D dependency and alopecia is described. She was a product of consanguineous mating and developed signs and symptoms suggesting vitamin D dependency early in life. Neither 150 microgram/day (6 microgram/kg.day) 1 alpha-hydroxyvitamin D3 nor 5 microgram/day (0.2 microgram/kg.day) 1,25-dihydroxyvitamin D3 proved to have an effect on her abnormal serum chemistry. Seven million international units per day (about 2 x 10(5) IU/kg.day) of native vitamin D restored her serum chemistry to normal and brought about marked improvement on skeletal radiographs, when her serum 25 hydroxyvitamin D, 1,25-dihydroxyvitamin D, and 24,25-di-hydroxyvitamin D were 4250, 4.8, and 35 ng/ml, respectively. Even with the high serum levels of vitamin D metabolites, her intestinal 47Ca absorption rate remained in the lower normal range and urinary calcium excretion was decidedly low. Association of hypoparathyroidism was ruled out. These results suggest that the patient has extreme and-organ (intestine) hyposensitivity, probably of congenital origin, to the biologically active metabolites of vitamin D. PMID- 6252223 TI - Angiotensin II receptors and in vitro aldosterone responses of aldosterone producing adenomas, adjacent nontumorous tissue, and normal human adrenal glomerulosa. AB - Angiotensin II (angio II) receptors have been compared using tissues from aldosterone-producing adenomas (APAs), adjacent nontumorus tissue, and normal human adrenal glomerulosa. Plasma membrane-rich subcellular fractions were employed in a radioreceptor assay with [125I]angio II. In vitro aldosterone secretory response to angio II were determined using isolated cells obtained by collagenase digestion. Results are reported as the mean +/- SE. Normal glands have high and low affinity receptor sites for angio II. The Ka values for a normal adrenal obtained at surgery were 2.5 and 0.4 nM-1, while autopsy adrenals were 1.1 +/- 0.4 and 0.3 +/- 0.15 nM-1 (n = 3). APAs and adjacent nontumorous tissue possessed only low affinity receptor sites (0.22 +/- 0.05 nM--1; n = 11). The receptor concentration for a surgically obtained adrenal was 1562 fmol/mg protein, contrasted with 466 +/- 135 from autopsy adrenals. APA and adjacent tissue bound 462 +/- 112 fmol/mg protein. Cells from seven of eight APAs produced aldosterone when stimulated by angio II (3 x 10(-10)-10(-6) m). The increments were 16-105% above basal levels. The response were similar to but less senstive than cells from normal adrenals. The only tumor that failed to respond had 1/50th of the receptors of the other APAs. In contrast, only three of seven adjacent tissues responded, and then only negligibly. ACTH (10(-8) M) increased aldosterone production by APAs 10-158%, by normal cells 283% and by three of six adjacent nontumorous tissues 170-400%. The observations that APAs have angio II receptors and aldosterone responses to angio II is consistent with the fact that some patients with APA have postural increments of plasma posture. The presence of receptors of adjacent tissue and no in vitro response suggest a defect in the aldosterone biosynthetic pathway as a cause of the prolonged absence of response to angio II after removal of APAs. PMID- 6252224 TI - Dopaminergic control of plasma catecholamine and aldosterone responses to acute stimuli in normal man. AB - This study examines the influence of dopamine on catecholamine and aldosterone secretion in normotensive individuals. The responses of plasma aldosterone (PA), norepinephrine (NE), and PRA to upright posture and isometric handgrip were studied in five normal males on a constant 50-meq Na intake before and after 4 days of administration of the dopamine agonist, bromergocriptine (BEC; 2.5 mg three times a day). In addition, the PA responses to graded angiotensin II and ACTH infusions were examined before and during BEC. Supine PA and PRA were not altered by BEC, but basal NE was reduced significantly (P < 0.01) from 204 +/- 29 to 98 +/- 12 pg/ml after BEC. There was an accompanying significant reduction in upright mean arterial pressure during BEC administration. The PA and NE during upright posture and isometric handgrip were significantly suppressed by BEC, but PRA responses were unaltered. BEC produced a significiant (P < 0.025) suppression of the PA response to graded angiotensin II infusions but did not alter the PA response to graded ACTH. Our findings indicate that in normal man there is a pronounced inhibitory effect of dopaminergic pathways on catecholamine scretion and regulation of upright mean arterial pressure. Results of the posture study would suggest that dopamine-mediated PA alterations occur independently of changes in the levels of PRA. The finding that BEC suppressed PA responses to angiotensin II and posture but not to ACTH would imply that dopamine selectively exerts its effect or adrenal angiotensin II-mediated aldosterone secretion. PMID- 6252225 TI - Glycogen metabolism of the human endometrium. AB - The glycogen concentration and the activities of glycogen synthetase and phosphorylase were assayed in endometrial tissue obtained during curettage. Tissues were obtained during different phases of the menstrual cycle from women investigated because of menometrorrhagia or sterility. The glycogen concentration was less than 2 mg/g wet wt in specimens from days 1-15 and increased 10-fold during the early secretory phase. The total activities of glycogen synthetase and phosphorylase were increased 1.5- and 2-fold, respectively, during the secretory phase compared to those during the first half of the cycle. The activities of the active forms (a form) of these enzymes did not show significant changes during the menstrual cycle. The largest difference between the proliferative and secretory phases was in the activity of glycogen synthetase phosphatase, which was virtually inactive in tissues obtained on days 1-15 and increased almost 20 fold during the secretory part of the cycle. In tissues obtained from cases of sterility, the activities of glycogen synthetase and phosphorylase were significantly reduced only during the early secretory phase. Glycogen concentration throughout the menstrual cycle and enzyme activities during the midsecretory and premenstrual phase were similar in cases of sterility and other pathologies. PMID- 6252226 TI - Human neurophysins as potential tumor markers for small cell carcinoma of the lung: application of specific radioimmunoassays. AB - A study of 61 patients with small cell carcinoma of the lung using specific RIAs for 2 human neurophysins (HNPs) has revealed that plasma levels of 1 or both HNPs are substantially elevated (> 3 times) in 62% of the patients before the commencement of therapy. These elevated HNPs may be a consequence of production/release by tumor. Eighteen patients with elevated plasma HNPs and 14 with normal values were followed during therapy. All of the patients with normal pre-therapy levels maintained these normal levels regardless of the course of their disease. For all patients with elevated HNP levels before therapy, there was good agreement between changes in these elevated values and clinically assessed responses. Partial or complete remission (12 patients) was associated with a 2- to 30-fold reduction in HNP levels, progressive disease (6 patients) was associated with a rise in HNP levels, and relapse after a previous objective response (6 patients) was associated with an increase in plasma HNPs over values found during remission. For many of the patients in clinical remission, HNPs remained elevated above normal values, and RIA data seem to forecast recurrent disease several weeks before clinical recognition. These data provide good evidence that our RIAs for HNPs can provide a valuable guide to therapeutic management of small cell carcinoma of the lung. PMID- 6252227 TI - Simultaneous determination of human plasma immunoreactive beta-lipotropin, gamma lipotropin, and beta-endorphin using immuno-affinity chromatography. AB - Since plasma ACTH, beta-lipotropin [beta-LPH-(1-91)], gamma-lipotropin (gamma LPH: [beta-LPD-(1-58)]), and beta-endorphin (beta-EP: [beta-LPH-(61-91)]) are all derived from a common precursor molecule, their quantification in the same plasma under basal and stimulatory conditions should help to elucidate factors involved in their secretion and regulation. A sequential immune affinity chromatographic procedure was used to separate immunoreactive beta-LPH, gamma-LPH, and beta-EP on individual patient samples. Basal morning plasma concentrations [femtomoles per ml (to convert values to picograms per ml, femtomoles per ml values are multiplied by 10 for beta-LPH, by 5.8 for beta-LPH, by 4.5 for ACTH, and by 3.4 for beta-EP; n = 19; mean +/- SEM)] were: beta-LPH, 6.1 +/- 0.8; gamma-LPH, 4.4 +/- 0.5; and ACTH, 11.1 +/- 1.3. beta-EP was undetectable (< 1.5 fmol ml-1) in 7 of the 19 basal samples. The mean +/- SEM for the 12 remaining samples was 2.3 +/ 0.2. Insulin-induced hypoglycemia and Pitressin administration were associated with nearly equivalent increments of immunoreactive ACTH and beta-LPH concentrations. The resolving power of the technique was tested by separately applying the immunoreactive beta-LPH, gamma-LPH, and beta-EP fractions obtained from plasma pools to Sephadex G-50 gel filtration for molecular weight estimation. Greater than 88% of all immunoreactive material eluted with a Kav similar to the appropriate standard peptide markers. This immune affinity chromatographic system, therefore, permits simultaneous quantification of these peptides on small plasma volumes more rapidly and with greater resolution than when molecular sieve chromatography is used as an adjunct to RIA. PMID- 6252228 TI - Anterior pituitary hormones in plasma and pituitaries from patients with Cushing's disease. AB - Pituitary adenomas were obtained from eight of nine patients with Cushing's disease, and the surrounding tissues as well were obtained from six of nine patients. ACTH, beta-lipotropin (beta-LPH), beta-endorphin, GH, TSH, LH, and PRL concentrations in these tissues were determined by RIA. Immunoreactive ACTH and beta-endorphin (beta-endorphin + beta-LPH) were present in high concentrations in all adenomas, and low concentrations were found in the surrounding tissues, except for one patient. As compared to levels seen in normal pituitary tissue, the GH concentration in the surrounding tissues was suppressed in five of six cases. TSH and LH concentrations were suppressed in four and three cases, respectively. The PRL concentration was not suppressed in any of the six patients studied. These four hormones were not detected in any adenoma. Plasma GH, TSH, and LH responses to various stimuli which were suppressed preoperatively returned to normal in most of the patients after adenomectomy. Basal plasma cortisol concentrations were normal or subnormal and were suppressed by the administration of 1 mg dexamethasone after adenomectomy, in contrast to the lack of such suppression preoperatively. ACTH and beta-endorphin secretion were stimulated by lysine-8-vasopressin and suppressed by dexamethasone and cyproheptadine in vitro. PMID- 6252229 TI - Luteinizing hormone receptors in ovarian follicles of patients with polycystic ovarian disease. AB - Wedge resection was performed in 12 patients with polycystic ovarian disease, and cell samples from the cystic follicles were assayed for LH(hCG) receptor using [125I]iodo-hCG as a ligand hormone. Simultaneously to wedge resection, blood samples were taken for serum FSH, LH, 17 beta-estradiol, progesterone, and testosterone RIA measurements. Serum LH was regularly elevated (16.0-57.1 U/liter), whereas FSH (5.2-11.5 U/liter) was within the normal reference range. The LH to FSH ratio was between 2.1-7.8. The 17 beta-estradiol concentrations (0.12-0.23 nmol/liter) were within the normal reference range found during the early follicular phase. Only 3 patients had progesterone levels exceeding the assay sensitivity limit of 0.1 nmol/liter. Ony 3 of the 11 patients assayed for serum testosterone had values exceeding the upper limit of the reference range. Seventy-seven percent of the ovarian follicular samples showed specific binding of [125I]iodo-hCG. The number of receptors in positive samples averaged 0.67 +/- 0.11 fmol/mg homogenate protein, which is clearly lower than that in normal preovulatory follicles. Scatchard analyses revealed a single class of binding sites, with a mean equilibrium association constant of 5.4 X 10(9) M-1 at 37 C. These results suggest that the derangement of follicular development in patients with polycystic ovarian disease probably is not due to the lack of appearance of the LH(hCG) receptor. It is possible that the tonic elevation of serum LH results in a decrease in the number of available receptor sites; this would be one step in the process leading to ovarian changes characteristic of this disease. PMID- 6252230 TI - Role of the renin-angiotensin system in enhancing the aldosterone response to adenocorticotropin during acute sodium depletion in normal subjects. AB - The role of the renin-angiotensin system in enhancing aldosterone responsiveness to ACTH during acute sodium depletion was studied in 14 healthy medical students. Acute sodium depletion was achieved by oral treatment with 80 mg furosemide and 200 mg SQ 14,225 for 1 day. The im administration of 250 micrograms alpha ACTH-(1 24) or vehicle was performed at 0800-0900 h both on the day after ad libitum diet (control) and 1 h after the oral administration of 50 mg SQ 14,225 on the day after acute sodium depletion. Treatments with furosemide and SQ 14,225 before both ACTH and vehicle administration induced a reproducible sodium depletion, accompanied by a marked increase in PRA and no significant increase in plasma aldosterone. The administration of ACTH, but not of vehicle, produced significant increases in plasma aldosterone in both control and acute sodium-depleted subjects. However, the ACTH-induced increases in plasma aldosterone and their maximal net and percent increments during acute sodium depletion were significantly greater than control values. It is concluded that angiotensin II does not play an important role in enhancing the aldosterone-stimulating activity of ACTH during acute sodium depletion and that sodium depletion per se may be responsible for this enhancement. PMID- 6252231 TI - Angiotensin II-induced aldosterone stimulation in man is not dependent upon adrenocorticotropin. AB - To document a possible role of ACTH in the aldosterone response to angiotensin II, we measured plasma aldosterone levels during physiological increments in plasma angiotensin II in normal male volunteers on two occasions, once with suppression of endogenous ACTH secretion (dexamethasone or hydrocortisone) and again without ACTH suppression. The subjects were studied under standardized conditions of dietary sodium (40 mmol/day) and potassium (100 mmol/day) intake and controlled body posture. Glucocorticoid pretreatment did not alter the plasma levels of angiotensin II attained during incremental infusions (0.5, 1, 2, and 4 ng/kg . min) of the octapeptide. Baseline plasma aldosterone levels were significantly lowered by glucocorticoid pretreatment. However, aldosterone responsiveness to infused angiotensin II (change and percentage of change from baseline levels) was not altered by suppression of endogenous ACTH production. Serum potassium levels were not increased by the administration of angiotensin II. The results demonstrate that in normal males on a sodium-restricted diet, baseline aldosterone levels are controlled in part by ACTH. The aldosterone response to angiotensin II, however, is not dependent upon endogenous ACTH secretion, an action of angiotensin II on the pituitary to release ACTH, or a rise in serum potassium. PMID- 6252232 TI - Anaphylactic shock after synthetic adrenocorticotropin-(1-18) in a patient with isolated adrenocorticotropin and beta-lipotropin deficiency. AB - A 58-yr-old woman had frequent hypoglycemic attacks, undetectable levels of plasma cortisol, ACTH, and beta-lipotropin, and deficient responses of these hormones after insulin induced-hypoglycemia and metyrapone. Her GH responses to arginine infusion were normal as were her gonadotropin responses to LRH. Her TSH and PRL responses to TRH were abnormally high. Anaphylactic shock occurred after the injection of either synthetic ACTH-Z-(1-24) (Cortrosin-Z) or ACTH-(1-18) (Acthormone). She had received two prior injections of synthetic ACTH-Z-(1-24) 2 months earlier. Circulating anti-ACTH antibody was found in her plasma by radioimmunological methods, but this antibody did not prevent corticosterone production by ACTH in an in vitro ACTH bioassay system. The pathogenic significance of this antibody in the ACTH deficiency is doubtful, and the etiology of the isolated ACTH and beta-LPH deficiency is not clear. PMID- 6252233 TI - Primary aldosteronism due to unilateral adrenal hyperplasia. AB - A 45-yr-old man with hypertension, hypokalemia, low plasma renin, and hyperaldosteronism was studied. Plasma and urine aldosterone were consistently above normal, remaining abnormally high even on a 300-meq sodium intake. Plasma aldosterone had a marked circadian rhythm, which was correlated with plasma cortisol. Aldosterone secretion was temporarily suppressed after dexamethasone administration and was stimulated by exogenous ACTH. The effect of posture was variable in the eight studies performed, possible due to episodic secretion of aldosterone observed near the sampling times of 0800 and 1200 h. Blood from the right adrenal vein contained 50--100 times more aldosterone than the left adrenal venous samples. The right adrenal gland was excised and found to contain many microscopic subcapsular nests of clear cells. Plasma aldosterone, renin, and potassium returned to normal after surgery, and blood pressure fell to 120/75 over the next 8 months. Three years later, the patient is normotensive without drugs. PMID- 6252234 TI - Twelve-hour cycles of adrenocorticotropin and cortisol secretion in Cushing's disease. AB - A 50-yr-old woman presented with a 7-yr history of Cushing's syndrome. She had high urinary free cortisol levels (711 micrograms/day) and a positive response to metyrapone and suppression with 8 mg dexamethasone, suggesting pituitary ACTH dependent adrenocortical hyperfunction. Plasma cortisol and ACTH levels showed marked temporal variation. Samples obtained at 2-h intervals revealed that plasma ACTH and cortisol levels surged during periods lasting approximately 12 h and fell to levels below normal during the remainder of the 24-h cycle. When urinary free cortisol was measured in urines collected in 12-h aliquots, the corresponding surge in free cortisol excretion was also evident. These cycles were not affected by a 2.5-month course of cyproheptadine. Pituitary irradiation and mitotane therapy resulted in remission of Cushing's syndrome, with disappearance of the peaks of ACTH and cortisol secretion. This case represents an unusual example of the abnormal circadian rhythm of ACTH secretion on Cushing's disease. PMID- 6252235 TI - Deficient activity of receptor-cyclase coupling protein in platelets of patients with pseudohypoparathyroidism. AB - Erythrocytes of patients with pseudohypoparathyroidism exhibit decreased activity of a membrane protein that is required for functional coupling of hormone receptors and catalytic adenylate cyclase. We observed decreased activity of this coupling protein in platelet extracts obtained from two pseudohypoparathyroid subjects, as compared with those of four normal control subjects. These findings support the hypothesis that generalized deficiency of this coupling protein is the primary biochemical defect of pseydohypoparathyroidism. PMID- 6252236 TI - Concomitant secretion of Y-MSH with ACTH and beta-endorphin in humans. AB - Using a specific radioimmunoassay for gamma-melanotropin (gamma-MSH), one of the predicted fragments in the amino-terminal portion of the adrenocorticotropin(ACTH)-beta-lipotropin (beta-LPH) precursor, gamma-MSH-like immunoreactivity (gamma-MSH-LI) was detected in human plasma from 4 of 5 patients with Addison's disease and 2 of 3 patients with Nelson's syndrome. None of the normal subjects or patients with Cushing's disease showed detectable concentrations (more than 150 pg/ml) of gamma-MSH-LI. gamma-MSH-LI was secreted concomitantly with ACTH-like immunoreactivity (ACTH-LI) and beta-endorphin-like immunoreactivity (beta-endorphin-LI) in response to insulin-induced hypoglycemia and the administration of lysine-vasopressin. Conversely, intravenous injection of cortisol lowered plasma concentrations of gamma-MSH-LI concomitantly with those of ACTH-LI and beta-endorphin-LI. Gel chromatographic studies of the plasma extracts showed a single peak of gamma-MSH-LI near the elution position of human beta-LPH. These results suggest that gamma-MSH-LI in human plasma is present as a big form and that this big gamma-MSH is secreted concomitantly with ACTH and beta endorphin. PMID- 6252237 TI - Detection of rotavirus by serological trapping on antibody-coated electron microscope grids. AB - A serological trapping technique for detecting rotaviruses is described which involves coating electron microscope grids with protein A and specific rotavirus antiserum. The presence of a layer of antibodies on the grid increases the number of rotavirus particles that can be visualized. Thirty-five crude fecal extracts from infants suffering from diarrhea were examined by the serological trapping technique and by standard electron-microscopy. When the specimens were deposited on antibody-coated girds, 71% of them were found to contain virus particles, compared with 20% on standard uncoated grids. The method is simple and rapid and does away with the need to concentrate the specimens. PMID- 6252239 TI - Gas-liquid chromatography of bacterial fatty acids with a fused-silica capillary column. AB - The use of flexible, fused-silica capillary column for gas-liquid chromatographic analysis of bacterial fatty acids is illustrated with Propionibacterium acnes, Propionibacterium shermanii, and a standard methyl ester mixture. PMID- 6252238 TI - Rotavirus-like, calicivirus-like, and 23-nm virus-like particles associated with diarrhea in young pigs. AB - Virus particles morphologically similar to caliciviruses and rotaviruses were detected by electron microscopy (EM) in the intestinal contents of a 27-day-old diarrheic nursing pig. A third small spherical 23-nm virus-like particle was also observed. Calicivirus-like particles averaged 33 nm in diameter. Similar to rotaviruses, rotavirus-like particles were present as single-capsid 55-nm forms or double-capsid 70-nm particles. Most gnotobiotic pigs orally exposed to samples containing these three viruses developed diarrhea and villous atrophy of the small intestine, and all shed the three viruses in their intestinal contents. Attempts to propagate these viruses in cell culture were unsuccessful. The antigenic relationship of the rotavirus-like particles to known rotaviruses was explored by immune EM and immunofluorescent staining. By these techniques, the rotavirus-like particles did not cross-react with antisera to porcine, bovine, or human rotaviruses or to reovirus type 3. Antisera from gnotobiotic pigs exposed to all three viruses had enzyme-linked immunosorbent assay and virus neutralization titers of <4 against porcine rotavirus. Previous infection of gnotobiotic pigs with the mixture containing rotavirus-like particles failed to protect them against a subsequent challenge with porcine rotavirus. The antigenic relationship of the calicivirus-like particles to known caliciviruses was investigated by immune EM and virus neutralization. By these tests, the calicivirus-like particles did not react with antisera against feline calicivirus strain 255 or M-8. In a study conducted at Plum Island Animal Disease Center, antiserum against the three combined agents did not specifically neutralize any serotype of swine vesicular exanthema virus. PMID- 6252240 TI - Evaluation of a clostridial alpha-toxin disk test for rapid presumptive identification of group B streptococci. AB - An alpha-toxin disk test is described in which group B streptococci completed the hemolysis of sheep erythrocytes partially lysed by the alpha-toxin of Clostridium perfringens. The test was performed satisfactorily on the sheep blood agar primary isolation plate, as well as on pure cultures. A total of 95% of strains of pure group B streptococci tested produced positive reactions within 5 h, and all were positive after overnight incubation, with patterns of synergistic hemolysis readily distinguishable from those seen with group A streptococci. The preparation of disks is well within the scope of most clinical laboratories. PMID- 6252242 TI - Role of infectious secretions in the transmission of rhinovirus. AB - In a series of studies aimed at investigating the role of environmental surfaces in the transmission of certain respiratory virus infections, it was shown that small amounts of nasal mucus containing rhinovirus (infectious mucus) can spread from fingertips to door knobs, faucet handles, or other environmental surfaces and remain infectious for many hours. These surfaces can serve as a reservoir of virus and may provide sufficient infectious material to contaminate hands. Recent studies have shown that once virus is on the fingers, it may be transferred to the nasal and conjunctival mucosa by means of autoinoculation. It has been estimated that as little as 1.0 plaque-forming unit can produce an infection in a susceptible human. In the present experiments, the amount of rhinovirus transmitted from fingers contaminated with infectious mucus to environmental surfaces and from there onto the fingers of a volunteer who touched the contaminated objects was quantitated, and the efficiency of transfer was studied. From 3 to 1,800 plaque-forming units of rhinovirus were recovered from the fingertips of volunteers (recipients) who handled either a door knob or a faucet that had previously been manipulated by another volunteer (donor) whose fingers were contaminated with infectious mucus. The average amount of rhinovirus recovered from the fingers of the recipients was approximately 13.5% of the amount recoverable from the fingers of the donor. In experiments in which there was direct hand-to-hand contact between donor and recipient, about 6.7% of the virus present on the fingertips of donors was recoverable from the recipients. PMID- 6252241 TI - Solid-phase enzyme immunoassay for determination of antibodies to cytomegalovirus. AB - A solid-phase enzyme immunoassay for the determination of immunoglobulin H (IgG) and IgM antibodies to cytomegalovirus is described. The enzyme immunoassay gave reliable and consistent results which were in concordance with those obtained by the complement fixation test and the indirect immunofluorescence test. Antibodies to herpes simplex and varicella-zoster viruses did not interfere in the enzyme immunoassay for cytomegalovirus IgM antibodies. In a few patients with IgM antibodies to Epstein-Barr virus, cytomegalovirus IgM antibodies were also detected. False-positive cytomegalovirus IgM antibody results were observed in sera containing both the rheumatoid factor and cytomegalovirus IgG antibodies. This rheumatoid factor interference was overcome by the absorption of sera with polymerized human gamma globulin. The absorption did not affect true cytomegalovirus IgM antibody titers. Also described is a simple enzyme immunoassay that makes possible a more sensitive detection of the rheumatoid factor than the latex agglutination test. PMID- 6252243 TI - Influence of residual moisture and sealing atmosphere on viability of two freeze dried viral vaccines. AB - This study demonstrated the complexity of the factors leading to changes in the infectivity titers of freeze-dried canine distemper and poultry infectious bronchitis viral vaccines. The change in moisture content during the storage period was an additional parameter which may influence the infectivity titer. The results emphasized the difficulty of predetermining variations in infectivity titers from the initial residual moisture. The analysis of the variations in infectivity titers during the storage of two vaccines led to the formulation of a hypothesis of the presence of two components of different thermostability. Moreover, the temporary increase in the infectivity titer of infectious bronchitis vaccine stored progressively dissociating during storage concurrent with a progressive inactivation of infectious particles. PMID- 6252244 TI - Enzyme-linked immunosorbent assay for detection of antibody in volunteers experimentally infected with human coronavirus strain 229 E. AB - An enzyme-linked immunosorbent assay was developed for detecting antibody rises to human coronavirus strain 229E and related strains in paired sera from infected volunteers. There was a close correlation between development of colds infected volunteers. There was a close correlation between development of colds and significant antibody rises detected by the enzyme-linked immunosorbent assay. Furthermore, the assay was more sensitive than a neutralization assay. This enzyme-linked immunosorbent assay is an easy, accurate, and sensitive assay for measuring significant antibody rises to human coronavirus strain 229E group viruses, and it could be useful in the clinical diagnosis of these infections. PMID- 6252245 TI - Evaluation of solid-phase immunofluorescence for quantitation of antibodies to herpes simplex virus and cytomegalovirus. AB - A recently developed semiautomated technique based on solid-phase immunofluorescence (FIAX) was compared with complement fixation for the determination of antibody levels to herpes simplex virus and cytomegalovorus in human serum samples. The results demonstrated that the FIAX method was in aggreement with the complement fixation technique for 97% of the serum samples tested. Reproducible titers were obtained from multiple FIAX determinations of representative sera within the same experimental run and between separate experimental runs. However, variability was rather high for patient sera with low (less than or equal to 1:5) antibody levels to cytomegalovirus. Hence, the results obtained by the FIAX technique were reproducible, and the FIAX system was as sensitive as complement fixation for the determination of antibody levels to herpes simplex virus and cytomegalovirus. PMID- 6252247 TI - New presumptive identification test for Clostridium perfringens: reverse CAMP test. AB - The reverse CAMP test proved to be a highly sensitive test since 97.0% of all Clostridium perfringens cultures tested gave an easily discernible positive reaction. PMID- 6252246 TI - Anticomplement immunofluorescence test that uses isolated fibroblast nuclei for detection of antibodies to human cytomegalovirus. AB - Cytomegalovirus antibodies were measured in human sera by a nuclear anticomplement immunofluorescence test that used as antigen the isolated nucleic of virus-infected fibroblasts cells lysed in distilled water. The method exhibited less nonspecific fluorescence than either a conventional whole-cell anticomplement immunofluorescence test or an indirect fluorescent antibody test applied to the same isolated nuclear substrate. The assay detected 97.5% of 40 antibody-positive sera, compared with 92.5 and 90% detection rates by indirect hemagglutination and complement fixation, respectively. In addition, antibody titers obtained by this technique were significantly higher than those obtained by either indirect hemagglutination (P < 0.02) or complement fixation with a glycine-extract antigen (P < 0.001). PMID- 6252248 TI - Role of oxygen in antibody-dependent cytotoxicity mediated by monocytes and neutrophils. AB - The antibody-dependent cell-mediated cytoxicity (ADCC) by human monocytes and neutrophils was investigated by measuring the release of 51chromate from prelabeled erythrocytes coated with immunoglobulin G. ADCC was found to be positively correlated to phagocytosis of 51Cr-labeled erythrocytes and to the postphagocytic events of the effector cells, activation of the hexose monophosphate shunt, and degranulation. Exclusion of oxygen from the incubation media halved the ADCC by both cell types without affectijg phagocytosis or degranulation. Likewise, ADCC by cells from patients suffering from chronic granulomatous disease (CGD) was only half the intensity of ADCC by cells from normals. Inhibitors of mitochondrial respiration were without depressing effect of ADCC. Azide, which in addition to its blocking action on oxydative phosphorylation also inhibits catalase and myeloperoxidase, resulted in a approximately equal to 40% stimulation of ADCC by cells from normals but was without effect of ADCC by cells from CGD patients. The hydroxyl radical scavenger, mannitol, significantly depressed ADCC by cells from normals (P < 0.01) but was without effect on cells from CGD patients. Azide and mannitol also were without effect on ADCC by normal cells when oxygen was excluded. In a xanthine-xanthine oxidase system, erythrocytes were effectively lysed. This lysis was inhibited by catalase, superoxide dismutase, and mannitol. When comparable concentrations of glucose oxidase were used no lysis was observed. H2O2 either alone or in combination with azide did not lyse erythrocytes. It is suggested that ADCC by both monocytes and neutrophils is partly dependent on the generation of hydroxyl radicals by the effector cells. PMID- 6252249 TI - Effect of insulinlike growth factor I on DNA and protein synthesis in cultured rat calvaria. AB - Insulinlike growth Factor I (IGF I), a growth hormone-dependent peptide or somatomedin, was studied for its effects on bone formation by examining the synthesis of DNA, collagen, and noncollagen protein in cultures of 21-d fetal rat calvaria. IGF I caused a dose-dependent stimulation of the incorporation of [3H]thymidine into DNA at concentrations of 0.1--100 nM; the effect appeared after 6 h, was maximal at 12 h, and was sustained for 96 h. IGF I also increased the bone DNA content, IGF I at 0.1--3 nM had a small stimulatory effect on the incorporation of [3H]proline into collagenase-digestible protein (CDP) whereas 30 nM IGF I caused a two- to threefold increment and had a maximal effect. A smaller effect on the labeling of noncollagen protein (NCP) was also observed. The effect of CDP and NCP appeared and was maximal after 12 h and was sustained for 96 h. IGF I increased the total collagen content of bones. The IGF I stimulatory effect on the incorporation of [3H]thymidine was seen in both the periosteum and periosteum-free calvarium, whereas that on the labeling of CDP was seen only in the central, osteoblastic-rich, non-periosteal bone. Histological sections showed a 10-fold increase in the mitotic index after Colcemid arrest in IGF I-treated bones, the mitoses were equally distributed in the periosteum and central portions of the calvarium. Insulin had a stimulatory effect on the incorporation of [3H]proline into CDP and NCP and 1 nM--1 microM similar to the effect of IGF I. In contrast, high insulin concentrations (0.1 and 1 microM) were required to increase the incorporation of [3H]thymidine, and insulin did not affect DNA content. Cortisol decreased the stimulatory effect of IGF I on DNA labeling but greatly enhanced the stimulatory effect of IGF I on the incorporation of [3H]proline into CDP. Triiodothyronine and parathyroid hormone increased the incorporation of [3H]thymidine and were additive to IGF I. Triiodothyronine did not affect the labeling of CDP, but parathyroid hormone inhibited it and opposed the effect of IGF I. These studies indicate that IGF I stimulates bone DNA, collagen, and NCP synthesis in vitro. IGF I and insulin have similar effects on bone collagen synthesis but IGF I stimulates the synthesis of DNA at physiological concentrations, and insulin does not. PMID- 6252251 TI - Interactions among lumbar motoneurons on opposite sides of the frog spinal cord: morphological and electrophysiological studies. AB - Light and electron microscopy have been used to study the projections of dendrites from motoneurons in lumbar segments of the spinal cord of the frog following administration of horseradish peroxidase to cut ventral roots. Processes originating from motoneurons crossed to the opposite side of the spinal cord via the anterior commissure and made contact with dendrites and motoneuronal somata. Typically, in segments 6 to 8 the crossing dendrites showed irregular enlargements in diameter. Electrophysiological recordings were obtained both extracellularly from ventral roots and intracellularly from motoneuronal somata. In Ringer's solution containing 1 mM calcium, stimulation of a lumbar ventral root, elicited population responses with early and late components in the ventral root of the opposite side of the same segment. Only the early, short latency component remained in calcium-deficient Ringer's solution. In calcium-containing Ringer's solution, intracellular recording from an antidromically activated motoneuron showed an action potential with a short latency; this response was followed by excitatory postsynaptic potentials (epsps) from which action potentials could be generated. Contralateral ventral root stimulation also elicited in the same motoneuron a short latency action potential that was rarely followed by epsps. The short latency responses, that were elicited by stimulation of ventral roots of either side persisted in calcium-deficient Ringer's solution, but the epsps were abolished. Contralaterally elicited short latency responses were eliminated by section of the anterior commissure. We believe that electrically mediated crossed interactions among lumbar motoneurons may serve as a means of coordinating muscle groups of opposite sides that are used in movements that require bilateral synchronization, such as jumping and swimming. PMID- 6252250 TI - Stimulus-specific deactivation of chemotactic factor-induced cyclic AMP response and superoxide generation by human neutrophils. AB - The responses of isolated human peripheral neutrophils to either simultaneous or sequential additions of two chemotactic factors were studied. Simultaneous additions of formyl-methionyl-leucyl-phenylalanine (10-100 nM) and the fifth component of complement, C5a (1-10 microliters/ml), evoked partially additive responses of membrane depolarization as measured by the fluorescent dye 3,3' dipropyl-thiocarbocyanine, a transient elevation of intracellular cyclic AMP (cAMP), and superoxide (O2-) generation as assessed by ferricytochrome c reduction. Preincubation of the cells with either formyl-methionyl-leucyl phenylalanine or C5a alone caused dose-dependent inhibition of the depolarization, the cAMP increase, and O2- release induced by a subsequent exposure to an optimal dose of the same stimulus, i.e., deactivation occurred. In contrast, when cells were treated with one chemotactic factor and then exposed to the other stimulus, the cells exhibited a normal response of peak depolarization, the rise in cAMP, and O2-0 production i.e., cross-deactivation failed to occur. The results imply that deactivation of these phenomena is stimulus specific. Further, these observations are consistent with the hypothesis that cross deactivation of chemotaxis is mediated by one or more processes that are irrelevant to O2- generation, and that occur distal to the depolarization and cAMP steps in the sequence of neutrophil activation: possibly microtubule polymerization and orientation. PMID- 6252252 TI - Fluorescence and electron microscopical observations on the amine-accumulating neurons of the cebus monkey retina. AB - The organization of the Cebus monkey regina was analysed after the intraocular injection of 5,6-dihydroxytryptamine. This amine was taken up not only by the previously known dopaminergic neurons, but also by a set of indoleamine accumulating neurons, whose processes are confined to the inner plexiform layer. The synaptic contacts of the dopaminergic neurons were analysed in the electron microscope after the processes of the indoleamine-accumulating neurons were destroyed by the intravitreal injection of the neurotoxic indoleamine, 5,7 dihydroxytryptamine. The subsequent injection of 5,6-dihydroxytryptamine induces certain changes in the dopaminergic neurons which accumulate the substance: electron-dense cores appear in the synaptic vesicles, and increased electron density of mitochodrial and cellular membranes is often observed. The dopaminergic neurons were found to be presynaptic to amacrine cell perikarya and processes in the inner plexiform layer. In the outer plexiform layer they were presynaptic to both bipolar and horizontal cells, but they did not contact photoreceptors. The dopaminergic neurons received synapses only in the inner plexiform layer, from amacrine cell processes. It is inferred that in Cebus most dopaminergic neurons belong to a special class of retinal neuron, the interplexiform cells, which appear to transmit information centrifugally within the retina, from the inner to the outer plexiform layers. There are considerable similarities between the synaptology of the dopaminergic interplexiform neurons in the Cebus monkey and the goldfish retina, and the function of interplexiform neurons may therefore be similar in these two species. PMID- 6252253 TI - Inappetence in ruminants as a measure of fluoride solubility in various phosphates. AB - Experiments with soft phosphate and fertilizer grade concentrated superphosphate and diammonium phosphate were to measure effects on voluntary intake of their fluoride in relation to that from calcium fluoride and sodium fluoride given once daily by capsule. Mature wethers were offered 1200 or 1400 g daily of mixed grain roughage diet, and responses to fluoride were measured by inappetence, consumption of less than 10% of offered diet. When 40 ppm fluoride as sodium fluoride was given for 2 days, inappetence resulted, whereas 2,400 ppm fluoride as calcium fluoride did not decrease feed intake. Time required for recovery of appetite increased with more fluoride. When soft phosphate, concentrated superphosphate, and diammonium phosphate were tested at 100, 200, and 400 ppm fluoride, inappetence occurred always but severity of reduction of intake was related to parts per million fluoride. Solubility of fluoride in soft phosphate, concentrated superphosphate, and diammonium phosphate is more similar to sodium fluoride than to calcium fluoride, and their use should be in keeping with fluoride tolerances established for ruminants fed sodium fluoride. PMID- 6252254 TI - Eccrine poroma. PMID- 6252255 TI - Contact sensitivity in mice induced by tolylene diisocyanate (TDI). PMID- 6252256 TI - [Renal excretion of water and electrolytes during chronic stimulation of the peripheral nervous system]. PMID- 6252257 TI - Firm, raised mass of the buccal mucosa. AB - Although the exact origin of the granular cell tumor is unknown and theories on histogenesis are controversial, some characteristics of the lesion are certain. The granular cell tumor behaves benignly, usually affects persons in the fourth decade, and has a predilection for females. The most significant aspect is the presence of extensive hyperplasis of the overlying surface (pseudoepitheliomatous hyperplasia) in 50% to 65% of the cases. PMID- 6252258 TI - Specific modulation of complement-dependent human granulocyte function by imidazole acetic acid. AB - Because imidazole acetic acid (IAA), a product of histamine catabolism was shown to inhibit histaminase release from human polymorphonuclear leukocytes (PMNs), the effect of this compound on other neutrophil functions was investigated. IAA at concentrations of 10(-10) or more inhibited histaminase release induced by particle-bound C3b, the larger fragment of the activated form of the third component of complement. Release of histaminase induced by aggregated IgG, phorbal myristate acetate (PMA), formyl-methionyl-leucyl-phenylalanine (FMLP) and calcium ionophore was not affected by IAA. In addition IAA had no effect on release of beta-glucuronidase, myeloperoxidase, and lysozyme or on phagocytosis and superoxide generation. IAA did modestly inhibit neutrophil chemotaxis. These findings suggest a highly specific modulating effect of the histamine catabolite IAA on complement-mediated PMN function. PMID- 6252259 TI - Crystal-associated arthropathies: what's new in old joints. AB - Degenerative arthritis in the aged includes two major disease categories- osteoarthritis and the crystal-associated arthropathics. The crystals chiefly involved are monosodium urate (gout) and calcium pyrophosphate dihydrate (CPPD), although several others (e.g., cholesterol, brushite and apatite) have been implicated. This report illustrates how the newer diagnostic techniques such as polarized-light microscopy, analytical electron microscopy and x-ray microdiffraction have augmented knowledge concerning diseases associated with articular crystal deposition. For example, diffraction techniques are required for accurate identification of the apatite crystals found in synovial fluid effusions and in the matrix vesicles of degenerate cartilage. According to ultrastructural studies, monosodium urate crystals found in tophi, joint surfaces and effusions show a distinct morphology. Present in inactive joints, the crystal surfaces are bare; in acute gout, the crystals are covered with mucin, confirming the observation that protein binding to crystals is necessary for inflammation to proceed. CPPD disease is by far the most common crystal-associated arthropathy affeting the aged. The incidence of CPPD deposits in articular tissues increases with age but, in contrast to gout, affects both men and women. The pathogenesis of CPPD disease is a mystery, but factors under investigation include matrix abnormalities, ionic imbalances, and enzyme disorders. PMID- 6252260 TI - The synthesis and characterisation of a cyclic AMP-Sepharose 4B matrix with affinity for cyclic AMP-dependent proteins. AB - A novel synthesis route for the preparation of a cyclic AMP-containing affinity adsorbent is described. This involves the use of a simple single-vessel, two step, solid-phase reaction in which 5'-AMP, originally coupled to the matrix in the form of 5'-AMP-Sepharose 4B, is cyclised by a sequence involving activation of the phosphate moiety, followed by intramolecular condensation to give a 3',5' phosphodiester. Physicochemical evidence, including 31P NMR studies, shows that this cyclisation takes place leaving no trace of original phosphomonoesters. The gel retains its excellent chromatographic properties, but now its specificity is directed towards cAMP-dependent proteins. Protein kinase (EC 2.7.1.37) binds to the gel, the catalytic subunit only being eluted when a simple buffer 0.2 M phosphate/1 mM theophylline is applied to column, whilst the regulatory unit is eluted using 20% ethylene glycol of 2% Pharmalyte, pH 5-8. This gel should find a use in the purification of protein kinase subunits and, by inference, of other cAMP-dependent proteins. PMID- 6252261 TI - Rapid separation and quantitation of 3',5'-cyclic nucleotides and 5'-nucleotides in phosphodiesterase reaction mixtures using high-performance liquid chromatography. AB - A simple, rapid high-performance liquid-chromatography system for the fractionation and direct quantitation of substrates and products in crude phosphodiesterase reaction mixtures is described. Phosphate buffers and a pellicular anion exchange resin are used at ambient temperature. The method is sensitive, measuring picomoles of products with ultraviolet detection and femtomoles with isotopic measurement, and offers several advantages over the more popular batch sorption and manual methods for measuring phosphodiesterase activity. The time required for analysis, less than 8 min for single substrate reaction mixtures, is a fraction of that required with other chromatographic systems, and precision is +/- 5%. Results of studies with an activatable form of phosphodiesterase demonstrate the accuracy, precision and utility of the procedure for biochemical analyses. PMID- 6252262 TI - Improved methods for automatic monitoring of contracting heart cells in culture. AB - The present communication describes improved methods for isolating and plating beating heart cells from neonatal rats using collagenase and collagen-coated petri dishes. The amplitude and frequency of contraction are continuously and simultaneously measured under well defined conditions and during prolonged periods of time with a highly sensitive and thermostated instrument. Additions, e.g. drugs and toxic agents, are made through an accessory pump system that involves extensive dilution of the added compound with medium; aliquots of medium can be withdrawn for estimation of metabolites. The system described is reliable and relatively inexpensive and allows a more extensive use of isolated heart cells, especially in studies of heart functions where small changes in amplitude and frequency of beating during prolonged periods of time are important. PMID- 6252263 TI - Bilateral attritional rupture of the ulnar nerve at the elbow. AB - In a 56-year-old woman with severely deforming rheumatoid arthritis, surgical exploration demonstrated partial rupture of one ulnar nerve and complete rupture of the other. PMID- 6252264 TI - Induction of Epstein-Barr virus early antigen by phytohaemagglutinin in the presence of 5-iodo-2'-deoxyuridine: application to EBV serology. AB - Induction of EBV early antigens in the non-producer lymphoid cell line RAJI by treatment with PHA in the presence of IUdR has been shown to be a convenient and efficient procedure for the preparation of cells for EBV serology. This induction procedure results in significant levels of EA-D and EA-R positive cells. The serological titres obtained on cell preparations induced with PHA and IUdR were comparable to those obtained on smears prepared by the classical procedure requiring infectious EBV. This convenient method of induction can replace more cumbersome techniques for routine EBV serology. PMID- 6252265 TI - Oxygen toxicity. PMID- 6252266 TI - [Metabolism of membrane phospholipid and mode of hormone action (author's transl)]. PMID- 6252267 TI - [Elucidation of microstructures of biological chromophores by resonance Raman spectroscopy (author's transl)]. PMID- 6252268 TI - Ascorbate efflux from guinea pig and rat lungs. Effect of starvation and O2 exposure. PMID- 6252269 TI - Incorporation of glucosamine by activated human neutrophils. A myeloperoxidase mediated process. AB - Zymosan-activated neutrophils were found to incorporate large amounts of [3H]glucosamine into TCA-precipitable material as compared with resting cells. The burst of glucosamine incorporation began 2 min after zymosan exposure and lasted 3 to 5 min, after which the incorporation rate returned to that of resting cells. Studies with cells from patients with chronic granulomatous disease and hereditary myeloperoxidase deficiency as well as experiments with inhibitors indicated that glucosamine incorporation required both the respiratory burst and the myeloperoxidase system. SDS-polyacrylamide gel electrophoresis of [3H]glucosamine-containing TCA precipitates from zymosan-activated cells revealed radioactivity migrating throughout the length of the gel. The radioactivity in precipitates from resting cells or cells activated in the presence of a small amount of a myeloperoxidase inhibitor was found in a peak migrating close to the tracking dye. These results indicate that zymosan-activated neutrophils are able to incorporate glucosamine into protein by a process dependent on H2O2 and myeloperoxidase. The biosynthetic significance of this phenomenon is not certain, but it most likely represents the reaction of amino sugar with macromolecular degradation products formed by the action of the myeloperoxidase system on cellular and particulate constituents. PMID- 6252270 TI - Identification of testicular cell plasma membrane receptors for calcitonin. AB - Recent studies have suggested a role for CT in the serum and tissue zinc homeostatic mechanism. The effects of CT on zinc transport appeared to be most pronounced in testis and thymus. If these effects are physiologically important, a cell membrane CT receptor, similar to those described for other peptide hormones, ought to be demonstrable. Rat testicular and hepatic cell membranes were isolated on a linear 15% to 50% sucrose density gradient. Specific hormone binding was assessed by Scatchard analysis of the binding of a constant amount of radiolabeled hormone in the presence of known variable amounts of unlabeled hormone. Nonspecific binding was assessed by measurement of radiolabeled hormone binding in the presence of 10(3) molar excess of unlabeled hormone. Hepatic cell membrane demonstrated no specific binding of either 125I-synthetic human CT or 125I-synthetic 1-34 bovine PTH. Testicular cell membranes demonstrated no specific binding for PTH. CT, however, was specifically bound with a mean KD of 3.2 +/- 0.8 X 10(-8) (S.E.M.) mol/L (M). Specificity studies demonstrated no inhibition of CT binding of 10(2) molar excess of FSH, LH, 1-34 PTH, or insulin. These data suggest the presence of a specific plasma membrane receptor for CT in rat testes. The presence of a membrane receptor in this tissue is consistent with previous observations that CT can alter the zinc content of rat testis in vivo. PMID- 6252271 TI - The lipid composition and membrane fluidity of Dictyostelium discoideum plasma membranes at various stages during differentiation. AB - There are only minor changes in the amounts of the major lipid constituents of Dictyostelium discoideum plasma membranes during the early stages in the differentiation of this organism. By the time cells reach the pseudoplasmodial stage of development there are small increases in the amounts of phosphatidylinositol, phosphatidylglycerol, and lysophosphatidylethanolamine, and small decreases in the amounts of phosphatidylethanolamine and its plasmalogen form. There is also a slight decrease in the total amount of sterol in the plasma membrane during the transition from aggregation to pseudoplasmodium formation. However, no significant change in membrane fluidity as determined by electron paramagnetic resonance (EPR) accompanies these minor changes in lipid composition. It can be concluded that the establishment of cell-cell interaction in D. discoideum does not involve gross changes in plasma membrane fluidity or lipid composition. It was found that the plasmalogen form of phosphatidylethanolamine is a major phospholipid constituent in D. discoideum, and that this species is somewhat enriched in the plasma membrane.-Weeks, G., and F. G. Herring. The lipid composition and membrane fluidity of Dictyostelium discoideum plasma membranes at various stages during differentiation. PMID- 6252272 TI - Differentiation and function of rat adipocyte precursor cells in primary culture. AB - Precursor cells to adipocytes were purified from the epididymal fat pads of small rats and studied in primary culture. A culture system in which substrate and cofactors were not rate-limiting for complete adipocyte conversion was used by utilizing an agarose feeding-layer. Detachment of cells from the culture dish was prevented by addition of a viscous layer of culture medium, containing methyl cellulose. This system allowed quantitation and definite characterization of formed adipocytes, defined as cells accumulating a lipid droplet >20 micro m in diameter. The cells could be subcultured but then gradually lost their adipocyte conversion ability. Age of the donor depressed the adipocyte conversion which, however, never seemed to stop completely. Prostaglandin E(1) and F(2alpha) had no definite effect in the physiological concentration range while indomethachin possibly had a weak inhibitory effect. Insulin, heparin, and isobutylmethylxanthine increased adipocyte formation. Development of characteristic adipocyte functions with time was examined. Lipoprotein lipase activity was very low in the isolated precursor cells before culture, but developed in culture at confluence and was a thousand-fold higher within a few days. At this peak lipoprotein lipase activity was 50-fold higher than in mature adipocytes from the same donor animal. Triglyceride synthesis from glucose peaked in parallel but never reached the value of mature adipocytes and very little fatty acid was synthesized. Hormone-sensitive glycerol release developed at confluence and reached the level of activity of mature adipocytes. This study and previous work have indicated a role for the cyclase system in the development of adipocytes from precursor cells. Dibutyrylcyclic AMP caused an enhancement of lipoprotein lipase activity and adipocyte conversion. In suspension media, the nucleotide caused inhibition. These results are compatible with an effect of the nucleotide, not directly on lipoprotein lipase and cell determination, but via events taking place at confluence associated with cell to cell interactions. In comparison with previously described cells from an established cell line which undergo adipose conversion (3T3 cells), the cells described in the present work, like adipocytes, showed more metabolic activity in pathways for fatty acid incorporation from exogenous lipid sources (lipoprotein lipase activity) than from de novo synthesis. Furthermore, host-factors could be followed such as in the age- and site-dependence of adipocyte formation. Physiological stimuli such as insulin, lipid substrate, and heparin had effects on adipocyte formation. It was therefore concluded that this cell preparation has a potential of yielding information of physiological significance in studies of the regulation of adipocyte multiplication.-Bjorntorp, P., M. Karlsson, P. Pettersson, and G. Sypniewska. Differentiation and function of rat adipocyte precursor cells in primary culture. PMID- 6252273 TI - Squamous cell carcinoma of the thyroid gland. PMID- 6252275 TI - Virus-induced diabetes mellitus. XVIII. Inhibition by a nondiabetogenic variant of encephalomyocarditis virus. AB - Plaque purification of the M variant of encephalomyocarditis (EMC) virus resulted in the isolation of two stable variants: one diabetogenic and designated D and the other nondiabetogenic and designated B. When the D variant was inoculated into SJL/J male mice, hypoinsulinemia and hyperglycemia developed in > 90% of the animals. In contrast, none of the mice inoculated with the B variant developed diabetes. Histologic examination of pancreata from mice infected with the D variant revealed insulitis and necrosis of beta cells, whereas islets from mice infected with the B variant showed little, if any, change. When islets were assayed for infectious virus, approximately 10 times more virus was recovered from animals inoculated with the D as compared with the B variant. Moreover, approximately 60% of islet cells from mice infected with the D variant contained viral antigens when stained with fluorescein-labeled anti-EMC virus antibody, whereas < 5% of islet cells from animals infected with the B variant contained viral antigens. Co-infection experiments showed that the induction of diabetes by the D variant was inhibited by the B variant. When the B and D variants were mixed together at B:D ratios of 1, 9, and 99, diabetes developed in 60, 11, and 0% of the mice, respectively. Tissue-culture experiments revealed that the B variant induced considerably more interferon than the D variant, and studies in animals showed that interferon appeared earlier and in greater amounts in the circulation of mice infected with the B as compared with the D variant. These studies suggest that the induction of interferon by the B variant is, at least in part, responsible for the inhibition of diabetes by the D variant. PMID- 6252274 TI - Macrophage variants in oxygen metabolism. AB - Whereas phagocytic cells from normal individuals have the capacity to kill ingested bacteria and parasites, those from patients with several uncommon genetic deficiency diseases are known to be defective in bactericidal activity. Studies on neutrophils of these patients have revealed fundamental defects in their ability to reduce molecular oxygen and metabolize it to superoxide anion, hydrogen peroxide, and oxygen radicals. In the present experiments, we describe a clone of a continuous murine macrophage-like cell line, J774.16, that, upon appropriate stimulation, activates the hexose monophosphate shunt, and produces superoxide anion and hydrogen peroxide. With nitroblue tetrazolium to select against cells capable of being stimulated by phorbol myristate acetate to reduce the dye to polymer--formazan--which is toxic fot cells, we have selected for variants that are defective in oxygen metabolism. Four of these subclones have been characterized and found to be lacking in the ability (a) to generate superoxide anion, as measured by cytochrome c reduction; (b) to produce hydrogen peroxide, as measured by the ability to form complex I with cytochrome c peroxidase; and (c) to be stimulated to oxidize glucose via the hexose monophosphate shunt. These variants appear to represent a useful model for studying the molecular basis for macrophage cytocidal activity. PMID- 6252276 TI - Calcium flux across disk membranes. Studies with intact rod photoreceptors and purified disks. AB - Calcium accumulation by rod disks was studied in excised bullfrog retinas with 45Ca tracer-exchange methods. Ca uptake by disks is a necessary requirement if light-induced Ca releases from disks mediate photoreceptor excitation. In an hour long incubation, disks exchanged less than or equal to 0.01 mole of Ca per mole of rhodopsin, or less than or equal to 10% of their total Ca. This corresponds to a unidirectional flux of less than or equal to 0.01 fmol/cm2 S, or less than or equal to 5 ions/disk-second across the disk membrane. Neither incubation in 10 mM Ca (which increases cytoplasmic activity 10--100-fold) nor photostimulation (which photoactivated up to 50% rhodopsin/h) had measurable effect on exchange rate, though an increase of several orders of magnitude would have been expected according to the hypothesis. The observed exchange could not be explained by: (a) 45Ca losses from disks before measurement (neither the net efflux nor the Ca-Ca exchange property of disks adequately explains such losses), (b) a limited pool of exchangeables Ca from strongly binding intradiskal sites, or (c) rate-limiting flux across the plasma membrane during incubation. For the study of the Ca efflux properties of disks, separate experiments were performed with 45Ca-loaded disks. Intradiskal activity could be estimated from the disks' hyperosmotically sensitive 45Ca pool and from their intradiskal volume (indirectly assayed by density). Ca-Ca exchange was undetectable (less than or equal to 0.1 fmol/cm2 S) in disks whose intradiskal activity was at least 0.3 mM. Net efflux was 0.2 fmol/cm2 S for an intradiskal activity of approximately 1 mM and is comparable to published fluxes for phospholipid vesicles. These results seem to exclude the internal space of disks as the source of Ca for photoreceptor excitation. PMID- 6252277 TI - Sodium channels in presynaptic nerve terminals. Regulation by neurotoxins. AB - Regulation of Na+ channels by neurotoxins has been studied in pinched-off nerve endings (synaptosomes) from rat brain. Activation of Na+ channels by the steroid batrachotoxin and by the alkaloid veratridine resulted in an increase in the rate of influx of 22Na into the synaptosomes. In the presence of 145 mM Na+, these agents also depolarized the synaptosomes, as indicated by increased fluorescence in the presence of a voltage-sensitive oxacarbocyanine dye [diO-C5(3)]. Polypeptide neurotoxins from the scorpion Leiurus quinquestriatus and from the sea anemone Anthopleura xanthogrammica potentiated the stimulatory effects of batrachotoxin and veratridine on the influx of 22Na into synaptosomes. Saxitoxin and tetrodotoxin blocked the stimulatory effects of batrachotoxin and veratridine, both in the presence and absence of the polypeptide toxins, but did not affect control 22Na influx or resting membrane potential. A three-state model for Na+ channel operation can account for the effects of these neurotoxins on Na+ channels as determined both by Na+ flux measurements in vitro and by electrophysiological experiments in intact nerve and muscle. PMID- 6252278 TI - Interaction of n-alkylguanidines with the sodium channels of squid axon membrane. AB - The effects of n-alkylguanidine derivatives on sodium channel conductance were measured in voltage clamped, internally perfused squid giant axons. After destruction of the sodium inactivation mechanism by internal pronase treatment, internal application of n-amylguanidine (0.5 mM) or n-octylguanidine (0.03 mM) caused a time-dependent block of sodium channels. No time-dependent block was observed with shorter chain derivatives. No change in the rising phase of sodium current was seen and the block of steady-state sodium current was independent of the membrane potential. In axons with intact sodium inactivation, an apparent facilitation of inactivation was observed after application of either n amylguanidine or n-octylguanidine. These results can be explained by a model in which alkylguanidines enter and occlude open sodium channels from inside the membrane with voltage-independent rate constants. Alkylguanidine block bears a close resemblance to natural sodium inactivation. This might be explained by the fact that alkylguanidines are related to arginine, which has a guanidino group and is thought to be an essential amino acid in the molecular mechanism of sodium inactivation. A strong correlation between alkyl chain length and blocking potency was found, suggesting that a hydrophobic binding site exists near the inner mouth of the sodium channel. PMID- 6252279 TI - Separation of the action potential into a Na-channel spike and a K-channel spike by tetrodotoxin and by tetraethylammonium ion in squid giant axons internally perfused with dilute Na-salt solutions. AB - Squid giant axons internally perfused with a 30 mM NaF solution and bathed in a 100 mM CaCl2 solution, which are known to produce long lasting action potentials in response to pulses of outward current, were investigated. The effects of tetrodotoxin (TTX) and of tetraethylammonium ion (TEA+) on such action potentials were studied. The results are summarized as follows: (a) An addition of 1--3 microM TTX to the external solution altered but did not block the action potentials; it increased the height of the action potential by approximately 15 mV, and it decreased the membrane conductance as the peak of excitation by about two-thirds. (b) Voltage-clamp experiments performed with both NaCl and TTX in the external CaCl2 solution revealed that the TTX-insensitive action potential does not involve a rise in gNa, whereas the experiments performed without TTX showed that the action potential is accompanied by a large rise in gNa. (c) Internally applied TEA+ was shown to selectively block the TTX-insensitive action potential, but it did not block the other component of the action potential, which is accompanied by a rise in gNa, and which is selectively suppressed by TTX. (d) The addition of a small amount of KCl to the external CaCl2 solution containing TTX greatly increased both the maximum peak inward current under voltage clamp and the maximum slope conductance. Furthermore, it was shown that K+ applied on both sides of the axon plays a dominant role in producing the membrane potential in the active state in the presence of TTX, even though a large amount of Ca2+ is presented in the bathing medium. These observations have led me to conclude that the sodium channel is responsible for the production of the TTX-sensitive component of the action potential under the ionic conditions of these experiments, and the potassium channel for the TTX-insensitive component of the action potential. PMID- 6252280 TI - Interaction of deoxycholate with the sodium channel of squid axon membranes. AB - Deoxycholate can react with sodium channels with a high potency. The apparent dissociation constant for the saturable binding reaction is 2 microM at 8 degrees C, and the heat of reaction is approximately -7 kcal/mol. Four independent test with Na-free media, K-free media, tetrodotoxin, and pancuronium unequivocally indicate that it is the sodium channel that is affected by deoxycholate. Upon depolarization of the membrane, the drug modified channel exhibits a slowly activating and noninactivating sodium conductance. The kinetic pattern of the modified channel was studied by increasing deoxycholate concentration, lowering the temperature, chemical elimination of sodium inactivation, or conditioning depolarization. The slow activation of the modified channel can be represented by a single exponential function with the time constant of 1--5 ms. The modified channel is inactivated only partially with a time constant of 1 S. The reversal potential is unchanged by the drug. Observations in tail currents and the voltage dependence of activation suggest that the activation gate is actually unaffected. The apparently slow activation may reflect an interaction betweem deoxycholate and the sodium channel in resting state. PMID- 6252281 TI - Amino-sugar transport systems of Escherichia coli K12. AB - Glucosamine, mannose and 2-deoxyglucose enter Escherichia coli by the phosphotransferase system coded for by the gene ptsM. The glucosamine- and mannose-negative, deoxyglucose-resistant phenotype of ptsM mutants can be suppressed by a mutation mapping near ptsG that allows constitutive expression of the glucose phosphotransferase coded for by the gene ptsG. N-Acetylglucosamine enters E. coli by two distinct phosphotransferase systems (White, 1970). One of these is the PtsM system, the other is coded for by a gene which maps near the nagA,B genes at about min 15 on the E. coli chromosome. We propose that this gene be designated ptsN. Strains with either of these components of the phosphotransferase system will utilize N-acetylglucosamine as sole carbon source. PMID- 6252282 TI - Isolation and characterization of a mutant of Escherichia coli K12 synthesizing DNA polymerase I and endonuclease I constitutively. AB - A mutant of Escherichia coli K12, highly resistant to ultraviolet radiation, has been isolated. Preliminary tests show that this mutant is also resistant to mitomycin C, nalidixic acid, fluorouracil and thymineless death. The mutant strain apparently repairs its damaged DNA more efficiently than wild-type E. coli K12 strains and, to do so, constitutively produces 35 times more DNA polymerase I and 12 times more endonuclease I than the wild-type strain. PMID- 6252283 TI - Human cytomegalovirus DNA: physical maps for restriction endonucleases BglII, hindIII and XbaI. AB - It is proposed that the genome of human cytomegalovirus (HCMV) consists of two unique sequences, L and S, bounded by two sets of redundant sequences (P. Sheldrick et al. unpublished data). In this arrangement the terminal sequences (TR1 and TR8) are repeated in an intenal inverted form (IR1 and IR8) and delimit L and S. After restriction endonuclease cleavage of the DNA, four o.5 M and four 0.25 M fragments are found, indicating that HCMV DNA preparations consist of four equimolar populations differing only in the relative orientation of the L and S components. Cleavage of the CMV DNA with the restriction endonucleases BglII, HindIII and XbaI results in 32, 27 and 21 fragments, respectively. The arrangement of these fragments has been determined using molecular hybridization techniques, identification of terminal fragments and the identification of linkage groups by double-digestion. In this report the physical maps for the restriction endonucleases BglII, HindIII and XbaI are presented. PMID- 6252284 TI - The isolation and characterization of a clonally related series of murine retrovirus-infected mouse cells. AB - Starting with cloned NIH 3T3 mouse cells we have isolated a series of related lines infected with the Kirsten murine sarcoma/leukaemia (MSV/MLV) virus complex. These lines exhibit all three possible infected cell phenotopes: (i) transformed MSV/MLV producers; (ii) non-transformed MLV producers; (iii) transformed non producers. We have also selected non-transformed revertants from one of the non producer clones. This series of lines allows the study of the expression of the virus genome against a constant background of cellular gene expression. We have further characterized the lines with regard to anchorage dependence of growth, tumorigenicity and the presence of a rescuable sarcoma genome. The non-producer clones are uniform in their transformed properties. The revertants contain rescuable sarcoma virus, biologically indistinguishable from the original transforming virus, implying that the reversion is due to a change in cellular rather than viurs genetic information. PMID- 6252285 TI - Isolation and characterization of acyclovir-resistant mutants of herpes simplex virus. AB - Mutants of HSV which are resistant to acyclovir (acycloguanosine) have been isolated following serial passages of several herpes simplex virus (HSV) strains in the presence of the drug. The majority of the mutants isolated are defective in induction of thymidine kinase (TK) and this is consistent with the observation that independently isolated TK- viruses are naturally resistant to ACV. One mutant is described (SC16 R9C2) which is resistant in biochemically transformed cells which express HSV TK. This suggests that its resistance resides at a level other than TK. It is also resistant to phosphonoacetic acid, suggesting that the DNA polymerase locus may be involved. A further mutant is described [Cl (101) P2C5] which induces normal levels of TK, although the nature of resistance of this virus is not yet elucidated. PMID- 6252286 TI - Latency competence of thirteen HSV-1 temperature-sensitive mutants. AB - Thirteen temperature-sensitive (ts) mutants of HSV-1 were analysed for their capacity to establish latent infections in the brains of mice. Eleven of the mutants could be classified as latency-positive or -negative; two could not be assigned to either group. Leakiness of mutants in the brain and differences in particle/infectivity ratios were found not to play a role in the results. Ts+ revertants of selected latency-negative mutants regained the capacity to establish latent infections, indicating that it was the ts lesion in these agents which was involved in latency. Ultrastructural studies of neuroblastoma cells infected with various mutants and maintained at the restrictive temperature showed that no absolute correlations could be made between capacity to establish latent infection and synthesis of various morphologically identifiable virus products. Finally, from a comparison of latency characteristics with previously established polypeptide phenotypes of mutants it was concluded that one immediate early and one or more later virus functions are necessary for establishment and/or maintenance of the latent state. PMID- 6252287 TI - Modulation of Epstein-Barr virus release from cells by components of normal human serum. AB - By filtration of normal human serum through a Sephadex G-200 column, an anti virus release factor (AVRF), which is capable of inhibiting the release of Epstein-Barr virus (EBV) from cells cultured in vitro, was found in the fractions corresponding to IgM. Another component, antagonistic to the activity of AVRF, was found in the fractions close to those of albumin. Both AVRF and anti-AVRF were found in all sera from four EBV seropositive and three sero-negative adults tested. EBV-release inhibition by AVRF was reversible. AVRF did not neutralize virus infectivity or inhibit intracellular virus growth. Virus adsorption on to cells was not prevented by AVRF but cap formation of EBV antigens on cells was augmented by it. PMID- 6252288 TI - Requirements for DI particle prophylaxis against vesicular stomatitis virus infection in vivo. AB - In contrast to biologically active DI particles, neither u.v.-inactivated standard virus nor either of two different homologous u.v.-inactivated DI particles showed any prophylactic effect when injected intracerebrally into mice concomitantly challenged with VSV. Although u.v.-inactivated DI particles did not prevent death when given with the challenge virus, they did significantly lengthen the time until death occurred. Also, both u.v.-inactivated standard virus and DI particles protected mice against late challenge (at 3 or 10 days after treatment). Dosage titrations of preparations of two different active DI particles showed significant prophylaxis against simultaneous challenge with numbers of DI particles 10- to 100-fold lower than those which gave no prophylaxis when u.v.-inactivated. Thus, prophylaxis in this system in this system required biologically active DI particles. PMID- 6252289 TI - Morphogenesis of the assembly and release of bovine enterovirus. AB - Fluorescent antibody (FA) studies of cells infected with bovine enterovirus showed cytoplasmic blebs with specific fluorescence to the virus. These structures were also found extracellularly in the debris of lysed cells and were RNA-positive by acridine orange (AO) staining. The morphology of virus-infected cells was further studied by scanning electron microscopy (SEM). Transmission electron microscopy (TEM) with immunoferritin tagging showed the development of long sacs with bilaminated and multilaminated membranes. These sacs had multiple twists at different intervals along their length forming a chain of vesicles. The development and maturation of the virus were observed in these vesicles. A number of virus-containing vesicles were also present extracellularly in the debris of lysed cells. In addition, virus was observed in layers of membranous cisternae closely associated with vacuoles and plasma membrane. Some of the cisternae opened to the extracellular space and appeared to allow the release of the virus. Virus particles were also found in patches and in crystals within the cytoplasmic matrix. Many lysed cells contained fibrils often associated with patches of ferritin-tagged virus. This study presents morphological evidence for the release of the virus in vesicles after cell lysis, via cisternae with openings to the extracellular space, and in cytoplasmic blebs. PMID- 6252290 TI - Ultraviolet irradiation of herpes simplex virus (type 1): delayed transcription and comparative sensitivites of virus functions. AB - The delay in the replication of herpes simplex virus surviving u.v. irradiation occurs after the uncoating of virus, as judged by sensitivity to DNase. It occurs before translation, judged by the kinetics of appearance of various virus specific proteins, and before transcription, judged by the detection of virus specific RNA by in situ hybridization. Since the delays in both transcription and translation are reversed by photoreactivation, the simplest hypothesis is that pyrimidine dimers directly obstruct transcription;unless these are broken by photoreactivating enzymes, there will be transcriptional delay until reactivating processes have repaired the lesion. The u.v. sensitivities of the abilities to induce various enzymes (thymidine kinase, DNase and DNA polymerase) were only about four times less than that of infectivity. The The ability to induce the three enzymes was three times less sensitive than that of the structural antigen (Band II). PMID- 6252291 TI - Characterization and comparison of the DNAs of the three closely related bacteriophages gd, ge and gf with the genome DNA of the hydrogen-oxidizing host strain Pseudomonas pseudoflava GA3. AB - The double-stranded (ds)DNAs of the three closely related temperate Pseudomonas pseudoflava bacteriophages gd, ge and gf were studied biochemically and biophysically. The GC content of the DNA was 67.4 +/- 0.5% and differed only slightly from that of the host P. pseudoflava. By electron microscopic length measurements a mol. wt. of 26.1 X 10(6) to 26.7 X 10(6) was calculated for the three bacteriophage DNAs. Homogeneity of the bacteriophage DNAs was further demonstrated by specific cleavage with restriction endonucleases WcoRI and HindIII. It was concluded that the three homo-immune bacteriophages are identical. The genome size of the host P. pseudoflava GA3 was 3.7 X 10(9) as calculated from optical renaturation rate measurement with Xanthomonas pelargonii reference DNA. The bacteriophage gd genome thus amounts to 0.7% of the chromosome of this bacterial host. PMID- 6252292 TI - Enzyme-linked immunosorbent assay for coronaviruses HCV 229E and MHV 3. AB - The antigenic relationship between human cornonavirus strain 229E (HCV 229E) and mouse hepatitis virus strain 3 (MHV 3) was studied by means of the indirect form of enzyme-linked immunosorbent assay (ELISA). A cross-reaction was found with hyprimmune rabbit sera between HCV 229E and MHV 3 which may be due to the adherence of bovine serum componeants from tissue culture media, which were present on virus particles even after extensive purification. No cross-reaction was observed with immune sera absorbed with bovine serum, or with HCV 229E grown in tissue culture without serum. This indirect ELISA with HCV 229E may prove to be useful for studies with human sera. PMID- 6252293 TI - Temperature-sensitive mutants of equine arteritis virus. AB - Seventeen temperature-sensitive mutants of equine arteritis virus, a nonarthropod borne togavirus, have been isolated. 5-Fluorouracil, o-methylhydroxylamine and ethyl methanesulphonate were used as mutagens. The mutants were characterized by their ability to synthesize virus RNA and virus proteins at the permissive (35 degrees C) and restrictive temperature (40 degrees C) using autoradiography of cells labelled with 3H-uridine in the presence of actinomycin D and immunofluorescence respectively. Among the mutants, four were unable to synthesize virus RNA and virus proteins at 40 degrees C (RNA-/protein-). The other mutants were RNA-/protein+ (3); RNA +/-/protein- (2); RNA+/protein+ (6) and RNA+/protein- (1). PMID- 6252294 TI - Passively transferred myasthenia gravis: protection of mouse endplates by Fab fragments from human myasthenic IgG. AB - Using the mouse passive transfer model, the effects of purified human myasthenic immunoglobulin G and of the monovalent Fab fragment on neuromuscular junctions were investigated. Treatment with IgG markedly reduced amplitudes of miniature endplate potentials. When Fab fragments were transferred alone or with subsequent addition of IgG no neuromuscular transmission block was induced. Myasthentic IgG and Fab were specifically demonstrated at the neuromuscular junctions by immunohistochemistry. On electronmicroscopy endplate structure was normal in transfer experiments using IgG for up to 30 days. It is suggested that Fab fragments bind to acetylcholine receptors without affecting transmission and protect them from the attack of complete IgG antibodies. PMID- 6252295 TI - Neuromuscular transmission in the athymic nude mouse. AB - No major differences were observed in the mechanical properties of diaphragm, extensor digitorum longus and soleus muscles from athymic nude and control mice. Denervated soleus muscles from nudes and controls showed no significant differences in their sensitivities to the cholinoceptor agonists acetylcholine and carbachol, either in the absence or presence of the anticholinesterase, physostigmine, suggesting that postjunctional receptor function is essentially normal. Phrenic nerve-diaphragm preparations from nudes were less sensitive to the twitch-augmenting effects of neostigmine. No difference in the time course of endplate potentials (epps) between nudes and controls was seen either in the absence or presence of neostigmine. Hence the observed differences in twitch augmentation are unlikely to be due to differences in acetylcholinesterase activity in the two muscles. In normal mice miniature endplate potential (mepp) amplitude decreased and mepp frequency increased with age. These changes were associated with an increase in muscle fibre diameter and a concomitant decrease in membrane resistance. Such changes did not occur in nude mice; thus mepp amplitude remained, high as in young normal muscle. It is suggested that the thymus may play a role in muscle development and that the effects on neuromuscular transmission are secondary to changes in development. In cut diaphragm muscles transmitter reversal potentials in nudes and controls were not different. Although there was no difference in the amplitude of the first epp of a train, or in the immediately releasable acetylcholine store, the quantal content of the first epp, the probability of transmitter release, the total nerve terminal acetylcholine store and the transmitter mobilization rate were all reduced. It is considered probable that all the measurable differences in transmitter release can be explained in terms of the nude muscle fibre diameter being small and being associated with a small nerve terminal size. PMID- 6252296 TI - Effect of aminophylline and isoproterenol on spinal cord blood flow after impact injury. AB - A study of the effects of spinal cord injury upon spinal cord blood flow was carried out in cats. A 400 mg-cm impact produced an overall reduction in spinal cord blood flow of 24% in the white matter and 30% in the gray matter, as determined by 14C-antipyrine autoradiography. At the level of the injury, white matter flow was 8.1 ml/100 gm/min, a reduction of 49%, and in the gray matter, 12.5 ml/100 gm/min, a reduction of 76%. Treatment with aminophylline and isoproterenol improved the overall blood flow in the spinal cord. At the level of the injury, white-matter flow after this treatment was no longer significantly different from control values. The gray-matter flow remained decreased to 26.2 ml/100 gm/min, a reduction of only 47%. It is proposed that aminophylline and isoproterenol may increase cyclic adenosine monophosphate (AMP) and prevent platelet aggregation along the endothelial surfaces of the microcirculation, and may thereby help to maintain improved perfusion of the injured spinal cord. PMID- 6252297 TI - Atypical fibrous histiocytoma in the skull of an infant. Case report. AB - This is a report of an atypical fibrous histiocytoma in the skull of an infant, who at the age of 3 months was noted to have a "lump" beneath the scalp in the right parietal region. It was about 2 cm in diameter, and the scalp was movable over it. Physical examination was otherwise normal. Radiographs showed erosion of the scalp deep on the palpable mass. At operation a neoplasm was found, which had destroyed the bone and invaded the adjacent temporal muscle and dura mater. The tumor was removed en bloc after the surrounding bone had been excised. Histological examination using light and electron microscopy revealed the tumor to be an atypical fibrous histiocytoma. Radiation therapy was not given. There has been no recurrence for 7 years. PMID- 6252298 TI - Tc-99m HMDP (hydroxymethylene diphosphonate): a radiopharmaceutical for skeletal and acute myocardial infarct imaging. I. Synthesis and distribution in animals. AB - Technetium-99m hydroxymethylene diphosphonate (Tc-99M HMDP) is a new diphosphonate skeletal imaging agent. Animal studies show that Tc-99m HMDP has a higher uptake on bone and a more rapid clearance from the blood than any of the three technetium-labeled bone imaging agents in current use: Tc-99m methylene diphosphonate (DMP), Tc-99 (1-hydroxyethylidene) diphosphonate (HEDP), and Tc-99m pyrophosphate (PPi). On the basis of these animal studies, Tc-99m HMDP is a highly promising candidate for skeletal imaging. PMID- 6252299 TI - Tc-99m HMDP (hydroxymethylene diphosphonate): a radiopharmaceutical for skeletal and acute myocardial infarct imaging. II. Comparison of Tc-99m hydroxymethylene diphosphonate (HMDP) with other technetium-labeled bone-imaging agents in a canine model. AB - Technetium-99m hydroxymethylene diphosphate (Tc-HMDP) was compared with the two other diphosphonates (Tc-MDP and Tc-HEDP) and Tc-99m pyrophosphate (Tc-PPi) in a canine model of acute myocardial infarction. The TC-HMDP showed higher uptake in infarcted myocardium than the other two diphosphonates, and uptake equivalent to that of Tc-PPi. PMID- 6252300 TI - Absorption and excretion of cholecalciferol and of 25-hydroxycholecalciferol and metabolites in birds. AB - The absorption and excretion in vivo of cholecalciferol or 25 hydroxycholecalciferol (25-HCC) were determined in chicks (Gallus domesticus) and turkeys (Meleagris gallopavo). The overall net cholecalciferol or 25-HCC absorption in chicks and cholecalciferol in turkey poults was 66.5 +/- 3.3, 74.9 +/- 3.7 and 83.6 +/- 7.1% of the intake, respectively. The absorption of cholecalciferol or 25-HCC in chicks and turkeys occurred at the upper part of the intestine. 25-HCC, esters and non-polar metabolites of cholecalciferol or 25-HCC, and their polar metabolites, were secreted in the duodenum of chicks and turkeys but were partially reabsorbed at the upper part of the jejunum. PMID- 6252301 TI - Pyridoxine kinase, pyridoxine phosphate phosphatase and pyridoxine phosphate oxidase activities in control and B-6-deficient rat liver and brain. AB - The levels of pyridoxal phosphate in plasma, liver and brain and the activities of pyridoxine kinase, pyridoxine phosphate phosphatase and pyridoxine phosphate oxidase in liver and brain were measured over a 6-week period in rats fed pyridoxine-sufficient and pyridoxine-deficient diets. Consistently significant differences in enzyme activities between the two groups of animals were found only in pyridoxine kinase indicating that this enzyme plays a key role during the development of vitamin B-6 deficiency. Relative to control animals, the decrease observed in liver pyridoxine kinase acivity in animals fed pyridoxine-deficient diets is much greater than the decrease in brain pyridoxine kinase activity (50% decrease versus a 14% decrease after 5 weeks). In light of the suggestion that phosphorylation and binding to proteins serve to prevent the diffusion of B-6 vitamers out of cells, the differential response of pyridoxine kinase activity in liver and brain may be important in the maintenance of the vitamin B-6 supply in the central nervous system. During the course of this study, a new method for the determination of cellular phosphatase activity on a phosphorylated form of vitamin B-6 was developed. 3H-C4'-Pyridoxine phosphate was used as substrate and was separated from 3H-C4'-pyridoxine by means of anion-exchange filter paper disks. PMID- 6252302 TI - Bioavailability to rats of iron and zinc in wheat bran: response to low-phytate bran and effect of the phytate/zinc molar ratio. AB - Low-phytate wheat bran was produced by enzymatic hydrolysis and extraction. Rat bioassay methods were utilized to determine bioavailability of iron and zinc in the low-phytate brans and to study the effect of dietary phytate/zinc molar ratio on zinc bioavailability when the phytate source was bran. Endogenous phytase activity hydrolyzed 80-100% of the phytate when wheat bran was incubated in water overnight. The relative biological values of the iron in raw bran and phytate free bran were 98 and 113, respectively, compared to 100 for ferrous ammonium sulfate in a hemoglobin repletion assay. Low-phytate brans with phytate/zinc molar ratios of 8 or less were equivalent to zinc sulfate as dietary sources of zinc for growth of rats. Rats fed diets that contained wheat bran with zinc sulfate added to reduce the dietary phytate/zinc molar ratio from 40 or 50 to 20 grew at the same rate as rats fed a phytate-free diet, but femur zinc values were lower than those in the reference group. Gel filtration chromatography of extracts of raw and low-phytate brans suggested that zinc might be associated with phytate in wheat bran. PMID- 6252303 TI - Effect of refined cellulose on apparent energy, fat and nitrogen digestibilities. AB - Seven young women consumed a low cellulose diet for about 1 month and then the same diet for an additional month except that 16 g/day Solka Floc was added to the diet. Apparent digestibilities of energy, fat and nitrogen were measured for each subject during each diet. Digestibilities of fat and nitrogen were not affected by refined cellulose ingestion. Digestibility of nitrogen was 93.2% without and 92.9% with the Solka Floc, while fat digestibility was 96.3% during the control diet and 95.4% during the high cellulose diet. Mean digestibility of gross energy decreased significantly when cellulose was added to the diet, from 95.4% to 92.0% (P < 0.01). Undigested fecal fiber was the major source of the increased fecal energy. When fecal fiber energy was subtracted from total fecal energy and apparent energy digestibility recalculated, there was no difference in apparent energy digestibility during the 2 diets, 96.1% without and 95.6% with the Solka Floc supplement. Thus, ingestion of 16 g/day Solka Floc had no detrimental effect on the utilization of nitrogen and fat and increases in fecal energy could be explained by undigested refined cellulose. PMID- 6252304 TI - Effect of zinc deficiency on bone collagenase and collagen turnover. AB - The effect of zinc deficiency on bone collagenase activity and collagen turnover was studied in the chick. Zinc deficiency symptoms, evident after 8 days on the low zinc diet, included tibia deformities and decreased alkaline phosphatase. Bone collagen metabolism was markedly altered, with a significant reduction in collagen synthesis and turnover. Half-turnover time for tibia collagen was 13 days in the control and 35 days in the zinc-deficient chicks. Tibia collagenase activity was reduced by 40-80% in the zinc-deficient as compared to the control chicks. Heparin markedly increased collagenase activity in the zinc-deficient tibias elevating activity to control levels. But commercially available heparin was found high in zinc content which may explain this effect entirely. These data show that zinc deficiency decreases bone collagen turnover and probably accounts for the leg deformities seen in zinc-deficient chicks. PMID- 6252305 TI - Incidence of increased numbers of Clostridium perfringens in the intestinal tract of rats fed xylitol. AB - Sprague-Dawley rats were fed diets containing up to 20% xylitol for 49 days. When the rats were fed a xylitol regimen intended to produce adaptation to xylitol, approximately half of the animals adapted to xylitol and remained free from diarrhea during the feeding regimen. The other half did not adapt to xylitol and developed severe and persistent diarrhea accompanied by large volumes of intestinal gas. These non-adapted rats had significantly higher levels of intestinal tract Clostridium perfringens (10(6)--10(11) organisms per gram intestinal contents) than did control rats fed a xylitol-free cornstarch diet (0 10(4) organisms per gram). Rats adapted to dietary xylitol did not have detectable levels of C. perfringens in the gastrointestinal tract. PMID- 6252306 TI - Ultrastructural effects of sex hormones and infection on lymph node post capillary venules. AB - The ultrastructure of the lymph node post-capillary venules (PCV) was studied in control, gonadectomised and gonadectomised-Hexoestrol treated male and female mice, infected or not with Toxoplasma gondii. The percentage of the cytoplasmic area of the endothelial cells occupied by Golgi apparatus was estimated by quantitative stereology. The endothelial cells of the PCV are higher and contain more Golgi elements in female than male controls. Oophorectomy decreases the percentage of Golgi apparatus and the height of the endothelial cells while orchidectomy does not affect the former but increases the latter. The endothelial cells react to Hexoestrol similarly in male and female mice, by increasing their height and becoming more heavily structured, with an effect particularly on the Golgi apparatus. All groups of mice infected with Toxoplasma gondii, show increased numbers of lymphocytes passing through the wall of the PCV. The endothelial cells of the latter show increased numbers of ribosomes both free and attached to rough endoplasmic reticulum. Golgi elements are decreased. In view of these findings the mechanisms for selective lymphocyte migration through the walls of the PCV are discussed. PMID- 6252307 TI - Demonstration of IgG EA (early antigen) and IgM MA (membrane antigen) antibodies in CMV infection of healthy infants and in those with liver disease. AB - The sequence of antibody production to various virus-specific antigens in CMV infection in infancy was studied. In healthy infants, IgG EA antibody was demonstrated in 18% of cord sera, and disappeared within two months after birth in all cases not shedding virus. The nonmaternal EA antibody was produced following virus excretion and decreased rapidly following cessation of virus excretion. Thus, demonstration of EA antibody in infants after 2 months of age was found to indicate acquired CMV infection, even when CMV could not be isolated. IgM MA antibody did not persist as long as EA antibody, disappearing before cessation of virus excretion. Both IgG EA and IgM MA antibodies were more frequently demonstrated in infants with hepatitis than in healthy infants. These findings suggest the possible association of CMV with hepatitis in infants. PMID- 6252308 TI - Klinefelter syndrome, tumor, and sexual precocity. PMID- 6252309 TI - Successful treatment of chronic mucocutaneous candidiasis with ketoconazole. AB - Ketoconazole, a new oral antifungal agent, was evaluated in the treatment of four patients with severe chronic mucocutaneous candidiasis refractory to standard antifungal therapy. Three had Candida esophagitis, and too had previously received intravenous amphotericin B. Initial ketoconazole dosage was 100 mg daily for patients weighing less than 30 kg and 200 mg daily for patients over 30 kg. All four patients showed dramatic improvement on the initial dose; three had complete clearing of mucous membrane and skin lesions within three weeks. Of the three patients with Candida esophagitis, one had complete clearing of esophagitis within one month and two were markedly improved. One patient required 400 mg daily to obtain complete clearing of skin and mucous membrane lesions. Two patients were maintained free of overt disease on one dose three times weekly but two patients relapsed and have required daily ketoconazole therapy to keep them free of Candida. The only side effects were mild nausea (two patients) occasional emesis at higher doses (two patients), and transient hypocholesterolemia (one patient). No adverse hematologic, gastrointestinal, or renal effects were noted. Ketoconazole appears to be a valuable oral antifungal agent for some patients with CMC. PMID- 6252311 TI - Vitamin D-resistant rickets? PMID- 6252310 TI - Ampicillin-induced enterocolitis: implication of toxigenic Clostridium perfringens type C. PMID- 6252312 TI - Na+, K+-dependent ATPase activity and effect of K+ on in vitro protein synthesis and NAD pyrophosphorylase in Toxoplasma gondii. AB - Although Na+, K+-dependent ATPase activity was barely detectable in extracellular tachyzoites of Toxoplasma gondii, Mg++-dependent ATPase was readily demonstrable. Based on this finding, the effect of K+ on in vitro protein synthesis and NAD pyrophosphorylase of T. gondii was evaluated. Addition of KCl enhanced in vitro protein synthesis. NAD pyrophosphorylase also was activated by KCl. The optimal concentration of KCl for both enzymatic reactions was 150 mM. The supernatant fluid (15,000 g, 20 min) isolated from the homogenate of purified tachyzoites of T. gondii contained more Na+ than K+. Evaluation of leakage of Na+ and K+ from purified tachyzoites suggested that Na+ leaked more than K+. These observations suggest an important role of K+ in the regulation of the metabolism of T. gondii. PMID- 6252313 TI - Peroxide metabolism in the liver fluke, Fasciola hepatica. PMID- 6252314 TI - Human gingival fibroblast cell lines in vitro. II. Electron microscopic studies of fibrogenesis. PMID- 6252315 TI - Evidence of the directive effect of 17 beta-conjugate group on the enzymatic O methylation of catechol estrogen. AB - Incubations of 2-hydroxyestradiol (I), 2-hydroxyestradiol 17 beta-sulfate (II), and 2-hydroxyestradiol 17 beta-glucuronide (III) with purified rat liver catechol O-methyltransferase were carried out at pH 7.2 in the presence of Mg2+ and (3H Me)-S-adenosyl-L-methionine. The radioactive methylated products, 2 methoxyestradiol (IV) and 2-hydroxyestradiol-3-methyl ether (V), from each substrate were quantificanted by reverse isotope dilution method after their complete separation and acetylation. In the experiments of conjugated substrates, II and III, the analyses of the methylated products were done after their hydrolysis of 17 beta-conjugate groups with acid or beta-glucuronidase. The product ratios (2-methoxy/3-methoxy) of substrates I, II, and III, were 1:1, 4:1, and 45:1, respectively. These results are suggesting that 17 beta-conjugate groups of 2-hydroxyestradiol has directive effect on enzymatic O-methylation of estrogen catechols. Further, it is estimated that following process may be present in the estradiol metabolism in rat and/or humans: estradiol leads to estradiol 17 beta-conjugates leads to 2-hydroxyestradiol 17 beta-conjugates leads to 2-methoxyestradiol 17 beta-conjugates. PMID- 6252316 TI - High-pressure liquid chromatographic determination of ranitidine, a new H2 receptor antagonist, in plasma and urine. AB - An assay is described for the determination of a new H2-receptor antagonist, ranitidine, and its desmethyl metabolite in human plasma and urine. Alkalinized plasma or urine was extracted with methylene chloride, the organic phase was evaporated, and the reconstituted residue was analyzed by high-pressure liquid chromatography using a reversed-phase column. Two other identified metabolites of ranitidine, the S-oxide and N-oxide, were separated chromtographically from both ranitidine and the desmethyl metabolite. However, these metabolites could not be quantitative due to poor analytical recovery and interference from endogenous components. The sensitivity limits were 5 ng/ml for ranitidine and 15 ng/ml for desmethylranitidine. Plasma samples from two volunteers who were given oral ranitidine (0.1, 0.2, and 0.4 mg/kg) at 1-week intervals were assayed. Peak levels of 30--130 ng/ml were achieved between 40 and 120 min after dosage, followed by an elimination half-life of 2.9-3.9 hr. Plasma levels of ranitidine were still detectable at 8 hr but were below the sensitivity of the assay by 24 hr. Plasma levels of the desmethyl metabolite were seldom above the threshold sensitivity of the assay. Urinary excretion of unmetabolized ranitidine accounted for 77% of the administered dose, whereas only 4% appeared as desmethylranitidine. PMID- 6252317 TI - Complexes between pilocarpine and cobalt(II), nickel(II), copper(II), and zinc(II) ions. AB - The properties of pilocarpine as a ligand toward the halides of cobalt(II), nickel(II), copper(II), and zinc(II) were investigated. Pilocarpine behaved as a monodentate ligand, giving rise to compounds with the general formula methyl(pilocarpine)2X2. The coordinating geometry at the metal ion was pseudotetrahedral in every case. PMR studies showed that the pyridine-type nitrogen of the imidazole ring of pilocarpine was the donor atom of the ligand. PMID- 6252318 TI - T. L. Cleave and the fibre story. PMID- 6252319 TI - Laparoscopy in the management of gestational trophoblastic neoplasms. PMID- 6252320 TI - Comparison of four methods of analysis of 99mTc pyrophosphate uptake in rheumatoid arthritic joints. AB - Knees, hands, forearms and thighs in 22 patients with classical rheumatoid arthritis and 18 controls were imaged with 99mTc pyrophosphate. The uptake of 99Tc pyrophosphate in the joints of the hand and knee was quantitated using a gamma camera interfaced to a computer. Quantitative measurements of joint activity were assessed by analyzing resultant data in a number of ways. Counts per unit area normalized for body weight and dose of radiopharmaceutical was found to be the most satisfactory method of quantitating differences in disease activity. However, the sensitivity of the method was not great enough to clearly distinguish normal and rheumatoid joints. PMID- 6252321 TI - Investigation of the metabolic acitivity of bone in rheumatoid arthritis. AB - Uptake of 99mTc pyrophosphate was measured in the midthird of the radius, ulna femur and metacarpal bones of 22 men with rheumatoid arthritis and 18 control subjects. It was significantly elevated in the rheumatoid population. In a parallel study, the retention of 99mTc methylene diphosphonate was significantly increased in 12 of these rheumatoid patients compared to 6 of the control subjects. These results suggest that there is increased bone turnover occurring in "nonjoint" bone in patients with RA and that the use of such bone as a reference standard for joint imaging is likely to prove misleading. PMID- 6252322 TI - Novel analogues of enkephalin: indentification of functional groups required for biological activity. AB - Novel tri- and tetrapeptide analogues of enkephalin, in conjunction with earlier structure-activity data, confirm that chemical substitutents present in the first and fourth residues of enkephalin are required for in vitro biological activity. A class of arylamino and alkylamino derivatized tripeptides also were found to have significant in vitro opioid-like activity indistinguishable from [D-Ala2,D Leu5]enkephalin and morphine. PMID- 6252323 TI - Structure-activity relationships of pyrrole amidine antiviral antibiotics. 2. Preparation of mono- and tripyrrole derivatives of congocidine. AB - Representatives of three types of congocidine (1) analogues were synthesized. These were tested for cytotoxicity, inhibition of herpes simplex virus (HSV) replication in cultured cells, and effects on the synthesis of HS DNA in isolated nuclei in vitro, as well as on DNA synthesis by purified HSV DNA polymerase. All synthesized tripyrrole derivatives of congocidine were less cytotoxic and more active than the parent drug in all the three ant iviral tests. PMID- 6252325 TI - Fractures of the scapula. AB - One hundred thirty-seven fractures of the scapula in 121 patients were reviewed. The average age at the time of injury was 35 years, with fractures predominant in males (64%). The majority of cases (43%) involved fractures of the body of the scapula, with fractures of the scapular neck being second most common (26%). Automobile accidents produced the most injuries (52%), followed by auto pedestrian (18%), falls (12%), and motorcycle accidents (11%). Associated bony or major soft-tissue trauma was present in all but 15 of the 121 patients, the most common being fractured ribs in 44%. Other associated injuries included fractures of the clavicle (26%), fractured skull (24%), cerebral contusion (20%), neurologic deficit (13%), and pulmonary contusion or hemo-pneumothorax (16%). Patients with injuries involving the acromion process or acromioclavicular joint had a significantly higher incidence of associated peripheral nerve injuries than those with other fractures of the scapula, indicating that special attention should be given to the neurologic examination of patients with these fractures. Careful neurovascular examination is mandatory. Treatment was usually conservative, independent of the location of the fracture, with satisfactory long term results. We recommend simple immobilization followed by early active range of motion exercise. PMID- 6252324 TI - Neutralizing antibodies to simian papovavirus SA12 in Old World primates in laboratory colonies: high prevalence in baboons. AB - Sera from 517 laboratory-housed nonhuman primates representing five genera and from 13 laboratory workers were examined for the presence of neutralizing antibodies to SA12 virus. The antibody prevalences were as follows: baboons, 66%; patas and vervet monkeys, 24%; macaques, 8%, and chimpanzees, 2%. The serum of one laboratory worker had antibodies. These results suggest that SA12 virus is a common infection of nonhuman primates in laboratory colonies, especially baboons. PMID- 6252326 TI - Computed tomography in the assessment of patients with juvenile post-nasal angiofibroma. AB - Surgery for juvenile angiofibroma demands a knowledge of tumor size and site, the degree of lateral extension being of particular importance. This study compares information obtained from computed tomography with findings at time of surgery. Computed tomography is found to be a reliable and accurate means of tumor assessment. It is recommended that this should be an essential pre-operative investigation for patients with juvenile angiofibroma. PMID- 6252327 TI - Genomic masking and rescue of dual-tropic murine leukemia viruses: role of pseudotype virions in viral lymphomagenesis. AB - The kinetics of genomic masking of nondefective dual-tropic murine leukemia viruses (MuLV) by ecotropic MuLV in mixedly infected mouse cells was studied. The ratio of virus infection (ecotropic to dual-tropic) determined the kinetics of genomic masking. Some dual-tropic virus isolates could be masked routinely (i.e., converted to virions containing a dual-tropic genome and possessing the ecotropic host range) at all ratios of initial infection of mixedly infected mouse cells. The masked genomes could be rescued as infectious viruses of dual-tropic genotype and host range by an infectious center assay of the infected mouse cells on mink lung cells. Infectious center rescue of masked dual-tropic MuLV took place readily, even from cells that had been kept in continuous culture for many months after the onset of genomic masking. Some dual-tropic virus clones did not undergo genomic masking at any infection ratio with ecotropic virus. Nevertheless, such mixedly infected cultures also gave rise to phenotypically mixed virions, which contained a dual-tropic genome and had an ecotropic host range. (The phenotypically mixed virions found among the progeny of mixedly infected mouse cells were not pseudotypes, as both types of viruses were genetically nondefective, nor was the process leading to their generation a bona fide phenotypic mixing [Fischinger et al., Science 201:457-459, 1978]. Nevertheless, in this paper we use the terms pseudotype and phenotypic mixing because of the lack of a better description.) The lymphomagenic potential of dual-tropic lymphomagenic MuLV was compared with that of phenotypically mixed virions possessing an ecotropic host range and with that of a simple mixture of dual tropic and ecotropic viruses. The phenotypically mixed pseudotype virions were more potent lymphoma inducers than were those of dual-tropic, cloned genotype. Inoculation of a simple mixture of the viruses did not increase dual-tropic virus tumorigenicity. The reason for this was probably the highly efficient inactivation of dual-tropic virus by oncovirus-inactivating factor, which is present in normal mouse serum and did not inactivate the phenotypically mixed virions. Simple mixtures of dual-tropic lymphomagenic and ecotropic virus preparations behaved like the cloned, dual-tropic virus in vivo and were equally sensitive to oncovirus-inactivating factor in vitro. Thus, phenotypic mixing of dual-tropic and ecotropic MuLV with or without concomitant genomic masking may be a highly significant phenomenon in naturally occurring lymphomagenesis. It may also be important to use phenotypically mixed viruses in the procedures used for in vivo testing of lymphomagenic dual-tropic MuLV isolates. PMID- 6252328 TI - Comparison of Epstein-Barr virus strains of different origin by analysis of the viral DNAs. AB - Epstein-Barr virus (EBV) originating from Burkitt's lymphoma (P3HR-1 and CC34-5), nasopharyngeal carcinoma (M-ABA), transfusion mononucleosis (B95-8), and a patient with acute myeloblastic leukemia (QIMR-WIL) was isolated from virus carrying lymphoid cell lines after induction with the tumor promoter 12-O tetradecanoylphorbol-13-acetate. Viral DNA was analyzed by partial denaturation mapping and by use of the restriction endonucleases EcoRI, HindIII, and SalI and separation of fragments in 0.4% agarose. By using the restriction enzyme data of B95-8 (EBV) and W91 (EBV) obtained by Given and Kieff (D. Given and E. Kieff, J. Virol. 28:524-542, 1978), maps were established for the other virus strains. Comigrating fragments were assumed to be identical or closely related among the different strains. Fragments of different strains migrating differently were isolated, purified, radioactively labeled, and mapped by hybridization against blots of separated viral fragments. The results were as follows. (i) All strains studied were closely related. (ii) The number of internal repeats was variable among and within viral strains. (iii) B95-8 (EBV) was the only strain with a large deletion of about 12,000 base pairs at the right-hand side of the molecule. At the same site, small deletions of about 400 to 500 base pairs were observed in P3HR-1 (EBV) and M-ABA (EBV) DNA. (iv) P3HR-1 (EBV), the only nontransforming EBV strain, had a deletion of about 3,000 to 4,000 base pairs in the long unique region adjacent to the internal repeats carrying a HindIII site. (v) Small inserted sequences of 150 to 400 base pairs were observed in M-ABA (EBV) and B95 8 (EBV) at identical sites in the middle of the long unique region. (vi) Near this site, an insertion of about 1,000 base pairs was found in P3HR-1 (EBV) DNA. (vii) The cleavage patterns of P3HR-1 virus DNA and the results of blot hybridizations with P3HR-1 virus fragments are not conclusive and point to the possibility that in addition to the normal cleavage pattern some viral sequences may be arranged differently. Even though it is possible that small differences in the genome organization may have significant biological effects, the great similarity among different EBV strains does not favor the hypothesis that disease specific subtypes exist. PMID- 6252330 TI - Physical mapping of adeno-associated virus serotype 4 DNA. AB - The organization of adeno-associated virus serotype 4 (AAV 4) DNA was probed by using restriction enzymes. The cleavage sites of the following enzymes were mapped: BglII, BamI, HincII, KpnI, PstI, SalI, SstI, and XhoI. The orientation of transcription on the physical cleavage map was determined by locating the fragments which contain the 3' end of the mRNA. Strand separation gels were run for HinII fragments of AAV 4 DNA. By hybridizing AAV 4 mRNA to the resolved strands, the polarity of the DNA strands was identified. Restriction digestion of AAV 4 DNA sometimes produced terminal fragments which migrated in agarose gels as doublets. However, when AAV 4 DNA was prepared devoid of any single-stranded nicks, these terminal doublet bands were not observed upon subsequent restriction analysis. During these studies, the molecular weights of both AAV 4 and AAV 2 duplex DNA were measured and were found to be somewhat larger than previously reported (3.18 x 10(6) and 3.10 x 10(6), respectively). PMID- 6252329 TI - Sites of synthesis of viral proteins in avian sarcoma virus-infected chicken cells. AB - We determined the sites of synthesis of avian sarcoma virus-specific proteins in infected chicken cells by immunoprecipitation of the products synthesized in vitro by free and membrane-bound polyribosomes; 85% of Pr76, the precursor of the viral internal structural proteins (group-specific antigens), was synthesized on free polyribosomes, and 15% was synthesized on membrane-bound polyribosomes. Pr92, the lycosylated precursor of the viral glycoproteins (gp85 and gp35), was synthesized exclusively on membrane-bound polyribomes, which is consistent with its role as a membrane protein. When we investigated the site of synthesis of pp60src, the product of the avian sarcoma virus src gene, we found that 90% was synthesized on free polyribosomes, whereas 10% was detected on membrane-bound polyribosomes. The implications of these results with respect to the subcellular location of pp60src are discussed. PMID- 6252331 TI - Mutant analysis of herpes simplex virus-induced cell surface antigens: resistance to complement-mediated immune cytolysis. AB - BHK-21 cells infected with temperature-sensitive mutants of herpes simplex virus type 1 strain KOS representing 16 complementation groups were tested for susceptibility to complement-mediated immune cytolysis at permissive (34 degrees C) and nonpermissive (39 degrees C) temperatures. Only cells infected by mutants in complementation group E were resistant to immune cytolysis in a temperature sensitive manner compared with wild-type infections. The expression of group E mutant cell surface antigens during infections at 34 and 39 degrees C was characterized by a combination of cell surface radioiodination, specific immunoprecipitation, and gel electrophoretic analysis of immunoprecipitates. Resistance to immune lysis at 39 degrees C correlated with the absence of viral antigens exposed at the cell surface. Intrinsic radiolabeling of group E mutant infections with [14C]glucosamine revealed that normal glycoproteins were produced at 34 degrees C but none were synthesized at 39 degrees C. The effect of 2-deoxy D-glucose on glycosylation of group E mutants at 39 degrees C suggested that the viral glycoprotein precursors were not synthesized. The complementation group E mutants failed to complement herpes simplex virus type 1 mutants isolated by other workers. These included the group B mutants of strain KOS, the temperature sensitive group D mutants of strain 17, and the LB2 mutant of strain HFEM. These mutants should be considered members of herpes simplex virus type 1 complementation group 1.2, in keeping with the new herpes simplex virus type 1 nomenclature. PMID- 6252332 TI - Effect of defective interfering particles on plus- and minus- strand leader RNAs in vesicular stomatitis virus-infected cells. AB - Vesicular stomatitis virus-infected cells contain short RNA transcripts, called leader RNAs, which are coded by the exact 3' end of both the minus-strand and plus-strand nucleocapsid templates. The molar amounts of both the plus-strand leader RNA (which is templated from the minus-strand genome) and the minus-strand leader RNA (which is templated from the plus-strand antigenome) were determined both in standard-virus- and mixed-virus-infected cells by using end-labeled genome probes. The results demonstrate that the presence of defective interfering particles in the infecting virus stock decreases the amount of plus-strand leader RNA but increases the amount of minus-strand leader RNA found in the infected cells. In addition, considerably more minus-strand leader RNA per mole of nucleocapsid template is synthesized in mixed-virus-infected cells than plus strand leader RNA per mole of nucleocapsid template in both standard-virus- and mixed-virus-infected cells. PMID- 6252333 TI - Recovery of biologically active spleen focus-forming virus from molecularly cloned spleen focus-forming virus-pBR322 circular DNA by cotransfection with infectious type C retroviral DNA. AB - The genome of the Lilly-Steeves strain of spleen focus-forming virus (SFFV) was molecularly cloned in the plasmid vector pBR322. Infectious SFFV could be recovered by releasing the SFFV DNA from the vector, transfecting the released DNA onto NIH 3T3 cells, and rescuing the SFFV either by superinfection with helper virus or by cotransfection with molecularly cloned infectious helper viral DNA. By using transfections with SFFV DNA still attached to the plasmid vector, infectious SFFV activity could also be recovered with either method of rescue. Studies performed with these latter types of transfections indicated that only a portion of the SFFV genome was required for biological activity. Since gp52, a marker protein for SFFV, could be detected in all cultures from which adequate titers of biologically active SFFV were recovered, the results are consistent with the hypothesis that gp52 is necessary for SFFV-induced erythroblastosis and polycythemia. PMID- 6252334 TI - Correlation of RNA binding affinity of avian oncornavirus p19 proteins with the extent of processing of virus genome RNA in cells. AB - We purified the p19 proteins from the Prague C strain of Rous sarcoma virus, avian myeloblastosis virus, B77 sarcoma virus, myeloblastosis-associated virus 2(0), and PR-E 95-C virus and measured their binding affinities for 60S viral RNA by the nitrocellulose filter binding technique. The apparent association constants of the p19 proteins from Rous sarcoma virus Prague C, avian myeloblastosis virus, and B77 sarcoma virus for homologous and heterologous 60S RNAs were similar (1.5 x 10(11) to 2.6 x 10(11) liters/mol), whereas those of myeloblastosis-associated virus-2(0) and PR-E 95-C virus were 10-fold lower. The sizes and relative amounts of the virus-specific polyadenylic acid-containing RNAs in the cytoplasms of cells infected with Rous sarcoma virus Prague C, myeloblastosis-associated virus-2(0), and PR-E 95-C virus were determined by fractionating the RNAs on agarose gels containing methylmercury hydroxide, transferring them to diazobenzyloxymethyl paper and hybridizing them to a 70 nucleotide complementary DNA probe. In cells infected with Rous sarcoma virus Prague C we detected 3.4 x 10(6)-, 1.9 x 10(6)-, and 1.1 x 10(6)-dalton RNAs, in PR-E 95-C virus-infected cells we detected 3.4 x 10(6)-, 1.9 x 10(6)- and 0.7 x 10(6)-dalton RNAs, and in cells infected with myeloblastosis-associated virus 2(0) we detected 3 x 10(6)- and 1.3 x 10(6)-dalton RNAs. Each of these RNA species contained RNA sequences derived from the 5' terminus of genome-length RNA, as evidenced by hybridization with the 5' 70-nucleotide complementary DNA. The ratios of subgenomic mRNA's to genome-length RNAs in cells infected with myeloblastosis-associated virus-2(0) and PR-E 95-C virus were three- to five-fold higher than the ratio in cells infected with Rous sarcoma virus Prague C. These results suggest that more processing of viral RNA in infected cells is correlated with lower binding affinities of the p19 protein for viral RNA, and they are consistent with the hypothesis that the p19 protein controls processing of viral RNA in cells. PMID- 6252335 TI - Identification of poliovirus polypeptide P63 as a soluble RNA-dependent RNA polymerase. AB - A poliovirus-specific RNA-dependent RNA polymerase was isolated from a cytoplasmic extract of infected HeLa cells and was shown to copurify with a single virus-specific protein. The polymerase was isolated from cells labeled with [35S]-methionine and was fractionated from other soluble cytoplasmic proteins by ammonium sulfate precipitation, phosphocellulose chromatography, gel filtration on Sephacryl S-200, and chromatography on hydroxylapatite. The activity of the enzyme was measured by using either polyadenylic acid or poliovirion RNA as a template in the presence of an oligouridylic acid primer. A single virus-specific protein that had an apparent molecular weight of 63,000 (p63) was found to copurify with this activity. Host-coded proteins were present in reduced molar amounts relative to p63. Noncapsid viral protein 2 (NCVP2) and other viral proteins were clearly separated from p63 by gel filtration on Sephacryl S-200. Polymerase activity coeluted from the column precisely with p63. NCVP2 was totally inactive as an RNA polymerase and did not stimulate the polymerase activity of p63. The purified enzyme sedimented at about 4S on a glycerol gradient and thus appeared to be a monomer of p63. Two-dimensional gel electrophoresis of the polymerase protein indicated that it had an isoelectric point of about 7.5. Thus, the viral polypeptide, p63, as defined by the above physical parameters, is an RNA-dependent RNA polymerase that can copy poliovirion RNA when oligouridylic acid is used as a primer. PMID- 6252336 TI - Activation of mouse lymphocytes by vesicular stomatitis virus. AB - Vesicular stomatitis virus (VSV) is a mitogen for mouse spleen cells, and infectious virus is not required for mitogenesis. At concentrations between 10 and 100 microgram per culture, VSV stimulated DNA synthesis and blast transformation. Maximal activation by VSV occurred 48 h after culture initiation. Spleen cells depleted of T-lymphocytes by treatment with anti-Thy 1.2 and complement and those obtained from congenitally athymic BALB/c nu/nu mice were activated by VSV, suggesting that VSV is a B-cell mitogen. Activation of spleen cells was independent of the host in which the virus was grown, since VSV grown in BHK-21, HKCC, or MDBK cells was mitogenic. The mitogenesis was specific for VSV, since MDBK cell-grown WSN influenza virus was not a mitogen in this in vitro activation system, VSV-specific antibody prevented VSV mitogenesis, and VSV was mitogenic for spleen cells from C3H/HeJ mice which were resistant to mitogenesis by endotoxin. PMID- 6252337 TI - Avian myeloblastosis virus proteins in leukemic chicken myeloblasts. AB - We have analyzed the avian myeloblastosis virus proteins in two types of leukemic myeloblasts: established myeloblastic cell lines (DU 1765 and DU 11157) and leukemic myeloblasts obtained from the peripheral blood of a leukemic C/E Spafas chicken (no. 21957). Using monospecific antisera for immunoprecipitation and polyacrylamide gel electrophoresis, we have detected gag gene-related proteins in the myeloblasts. The DU 1765 and DU 11157 cells contained a p100 protein which possessed antigenic determinants of the viral proteins p27, p19, p15, and p12. The p100 was not found in leukemic myeloblasts from Spafas chickens, and pulse chase experiments showed that the p100 was not a precursor for the viral proteins. However, the p100 is present in uninfected line 15 chicken embryos. A pr76-like protein was identified in DU 1765 cells but migrated slightly further into gels than the pr76 of Spafas-derived leukemic myeloblasts. The Spafas derived myeloblasts produced a pr60, whereas the DU 1765 cells contained instead a related protein of 62,000 daltons. Using anti-avian myeloblastosis virus gp85 sera, a glycoprotein of 120,000 daltons (gp120) was detected in all the tested leukemic myeloblasts. The gp120 was also present, in low amounts, in uninfected embyonic spleen and yolk sac cells. The anti-gp85 sera also precipitated a 27,000 dalton protein (h27) in these same cells. Both the gp120 and h27 could not be detected in either uninfected or myeloblastosis-associated virus-infected fibroblasts. Limited peptide hydrolysis revealed that h27 is different from the viral structural protein p27. In conclusion, monospecific antisera for gag and env gene products of avian myeloblastosis virus did not precipitate any unique or aberrant avian myeloblastosis virus protein from leukemic myeloblasts. PMID- 6252338 TI - den V gene of bacteriophage T4 determines a DNA glycosylase specific for pyrimidine dimers in DNA. AB - Endonuclease V of bacteriophage T4 has been described as an enzyme, coded for by the denV gene, that incises UV-irradiated DNA. It has recently been proposed that incision of irradiated DNA by this enzyme and the analogous "correndonucleases" I and II of Micrococcus luteus requires the sequential action of a pyrimidine dimer specific DNA glycosylase and an apyrimidinic/apurinic endonuclease. In support of this two-step mechanism, we found that our preparations of T4 endonuclease V contained a DNA glycosylase activity that produced alkali-labile sites in irradiated DNA and an apyrimidinic/apurinic endonuclease activity that converted these sites to nicks. Both activities could be detected in the presence of 10 mM EDTA. In experiments designed to determine which of the activities is coded by the denV gene, we found that the glycosylase was more heat labile in extracts of Escherichia coli infected with either of two thermosensitive denV mutants than in extracts of cells infected with wild-type T4. In contrast, apyrimidinic/apurinic endonuclease activity was no more heat labile in extracts of the former than in extracts of the latter. Our results indicate that the denV gene codes for a DNA glycosylase specific for pyrimidine dimers. PMID- 6252339 TI - Herpes simplex virus phosphoproteins. II. Characterization of the virion protein kinase and of the polypeptides phosphorylated in the virion. AB - The protein kinase associated with purified herpes simplex virus 1 and 2 virions partitioned with the capsid-tegument structures and was not solubilized by non ionic detergents and low, non-inhibitory concentrations of urea. The enzyme required Mg2+ or Mn2+ and utilized ATP or GTP. The activity was enhanced by non ionic detergents and by Na+ even in the presence of high concentrations of of Mg2+, but not by cyclic nucleotides. The enzyme associated with capsid-tegument structures phosphorylated virion polypeptides only; exogenously added substrates (acidic and basic histones, casein, phosphovitin, protamine, and bovine serum albumin) were not phosphorylated. The major phosphorylated species were virion polypeptides (VP) 1-2, 4, 11-12, 13-14, 18.7, 18.8 and 23. VP 18.7 and VP 18.8 have not been previously detected, but may be phosphorylated forms of polypeptides co-migrating with VP 19. Of the remainder, only VP 23 has been previously identified as a capsid protein; the others are constituents of the tegument or of the under surface of the virion envelope. The distribution of the phosphate bound to viral polypeptides varied depending on the Mg2+ concentration and pH. In the absence of dithiothreitol, in vitro phosphate exchange was demonstrable in VP 23 and to a lesser extent in two other polypeptides on sequential phosphorylation frist with saturating amounts off unlabeled ATP and then with [gamma-32P]ATP. Analysis of the virion polypeptides specified by herpes simplex virus 1 X herpes simplex virus 2 recombinants indicates that the genes specifying the polypeptides which serve as a substrate for the protein kinase map in the unique sequences near the left and right reinterated DNA sequences of the L component. PMID- 6252340 TI - Restriction endonuclease mapping of unintegrated viral DNA of B- and N-tropic BALB/c murine leukemia virus. AB - Unintegrated linear and closed circular DNAs of B- and N-tropic endogenous BALB/c murine leukemia virus (MuLV) were extracted from newly infected mouse cells and cleaved with EcoRI, XhoI, PvuI, HindIII, SalI, XbaI, KpnI, SmaI, and PstI restriction endonucleases. The DNA fragments were separated by electrophoresis and analyzed by the Southern blot hybridization procedure. EcoRI did not cleave the two genomes. A physical map of 15 cleavage sites on B- and N-tropic genomes was constructed with the other restriction endonucleases. Identical cleavage sites of B- and N-tropic MuLV DNAs were found with all these enzymes. However, the N-tropic linear genome was found to lack about 75 base pairs at each end of the molecule. PstI, KpnI, and SmaI recognize a cleavage site at both ends of the linear molecules. And sequences derived from the 5' end of the RNA genome were found in the third left end of the linear DNA and at its extreme right-end terminus, suggesting the presence of redundant sequences. Two species of closed circular viral DNA were observed. The larger species has the same size as the linear molecule and appears to be a circularized form of linear DNA. The smaller species contains sequences common to both the linear and the larger circular viral DNA but seems to be deleted from sequences present at either one or both ends of the linear DNA. Therefore, the general structure of the linear and circular DNA species of these B- and N-tropic endogenous BALB/c MuLV appears analogous to the structure found with other retroviruses. PMID- 6252341 TI - Evidence for the Asiatic origin of endogenous AKR-type murine leukemia proviruses. AB - A restriction endonuclease cleavage map of the genome of AKV, the endogenous, ecotropic leukemia virus of AKR mice, has been derived. By using this map and analyzing DNA from congenic mice, we have defined four DNA fragments diagnostic for AKV proviruses. Analysis of DNAs from 10 strains of American laboratory mice revealed that all strains carrying inducible, ecotropic murine leukemia viruses yielded DNAs which contained the four DNA fragments diagnostic for AKV. Virus negative strains lacked these fragments in their DNA. Screening DNA from 23 additional mice revealed that, among these mice, only mice from Asia gave rise to the DNA fragments diagnostic of an AKV provirus. We conclude that all of the endogenous ecotropic murine leukemia proviruses in American laboratory mice are closely related since they share a common set of restriction endonuclease cleavage sites. These proviruses appear to derive from the East Asian ancestors of these mouse strains. Analysis of DNA from six selected mice with an additional restriction endonuclease showed that greater than 97% of the nucleotide sequences in each provirus are contigous and that these endogenous proviruses are indistinguishable from proviruses introduced by exogenous infection. PMID- 6252342 TI - Characterization of Aleutian disease virus as a parvovirus. AB - We characterized a strain of Aleutian disease virus adapted to growth in Crandall feline kidney cells at 31.8 degrees C. When purified from infected cells, Aleutian disease virus had a density in CsCl of 1.42 to 1.44 g/ml and was 24 to 26 nm in diameter. [3H]thymidine could be incorporated into the viral genome, and the viral DNA was then studied. In alkaline sucrose gradients, Aleutian disease virus DNA was a single species that cosedimented at 15.5S with single-stranded DNA from adeno-associated virus. When the DNA was analyzed on neutral sucrose gradients, a single species was again observed, which sedimented at 21S and was clearly distinct from 16S duplex adeno-associated virus DNA. A similar result was obtained even after incubation under annealing conditions, implying that the bulk of Aleutian disease virus virions contained a single non-complementary strand with a molecular weight of about 1.4 X 10(6). In addition, two major virus associated polypeptides with molecular weights of 89,100 and 77,600 were demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of virus purified from infected cultures labeled with [35S]methionine. These data suggest that Aleutian disease virus is a nondefective parvovirus. PMID- 6252343 TI - Two-dimensional analysis of proteins sedimenting with simian virus 40 chromosomes. AB - The nonhistone proteins sedimenting in low-salt glycerol gradients with simian virus 40 chromosomes were analyzed by two-dimensional gel electrophoresis, utilizing nonequilibrium pH gradients as the first dimension and sodium dodecyl sulfate-gel electrophoresis as the second dimension. By densitometric quantitation of the radiolabeled proteins present in each fraction of the gradients, it was possible to identify sedimenting with all or a fraction of the simian virus 40 chromosomes. VP-1 sedimented with simian virus 40 chromosomes; additional evidence for its binding to chromosomes was obtained by immunochemical techniques. Four proteins (Mr 25,000, pI 6.0; Mr 32,000, pI 7.2; Mr 35,000, pI 8.5; and Mr 80,000, pI 7.2) sedimented with specific subsets of chromosomes. PMID- 6252345 TI - Phenotypic transformation of the host cell enhances polyoma pseudovirion formation. AB - Phenotypic transformation of the host cell affected the formation of polyoma pseuodovirions. Polyoma virus infection of various transformed derivatives of mouse 3T3 cells resulted in the formation of predominantly pseudovirions, whereas infection of mouse 3T3 cells produced mainly polyoma virus. The effect that transformation of the host cell had on polyoma pseudovirus formation was further demonstrated by using phenotypic revertants isolated from some of the transformed cell lines. The revertants were characterized by their morphology, saturation densities, and colony-forming ability in methylcellulose suspension. By these criteria they were distinct from their transformed parents and similar to 3T3 cells. After infection, the revertants produced predominantly polyoma virus and few pseudovirus. Thus, for the cell lines used in this study, phenotypic transformation enhanced the formationof polyoma pseudovirions. PMID- 6252344 TI - Detection and characterization of mouse mammary tumor virus cell surface antigens: estimation of antigen abundance by protein A assay. AB - Antisera against the following mouse mammary tumor virus (MMTV) structural proteins were used to detect MMTV cell surface antigens: (i) the 27,000-dalton nucleoid protein, p27; (ii) the 36,000-dalton envelope glycoprotein, gp36; and (iii) the 52,000-dalton exterior envelope glycoprotein, gp52. We report here the development of an adherent-cell isotopic staphylococcal protein A (SPA) test (ISPAT) for MMTV structural proteins which allows for the detection of an MMTV membrane-associated antigen as well as an estimate of its relative abundance on the cell surface. This test demonstrated that the gp52 was the predominant MMTV cell surface antigen detected on both C3H and GR mouse mammary tumor cells. In a comparative study with anti-gp52 and anti-gp36 sera, SPA-specific binding with anti-gp36 serum was found to be only 5 to 6% of that obtained for the external virion glycoprotein, gp52. Both direct and indirect ISPAT indicated the presence of a low but detectable number of gp36 determinants on GR-MMTV cells; however, these gp36 determinants, unlike gp52 determinants, appeared to be exposed by the fixation procedure used. Only 0.9 to 1.1% of the gp52-specific binding was detected when anti-gp36 serum was allowed to react with viable cells. The binding of [125I]SPA achieved with anti-p27 serum was even less than that detected with gp36-directed reagents, indicating that p27 is not a cell surface antigen. The use of fluoresceinated SPA further demonstrated that p27 and gp36 reactivity was only associated with a small number of cells in each of the mammary cultures tested. When N-[4-(5-nitro-2-furyl)-2-thiazoly]-formamide-induced C3H bladder tumor cells were subjected to a gp52-directed ISPAT, the failure to detect gp52 specific binding demonstrated the specificity of this assay for MMTV gp52 expressing cells. In addition to detecting and characterizing MMTV cell surface antigens, the newly developed adherent cell assay could measure changes in the abundance of cell surface gp52. When dexamethasone-treated and untreated GR cells were compared, measurements of gp52-specific SPA binding indicated that dexamethasone stimulation leads to a 12.2-fold increase in the amount of cell surface gp52 detected. PMID- 6252346 TI - Preparation and characterization of specific antisera to individual glycoprotein antigens comprising the major glycoprotein region of herpes simplex virus type 1. AB - The major glycoprotein complex (VP123) of herpes simplex virus type 1 resolved by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis was purified and further fractionated into two major and two minor components by chromatography of the isolated VP123 region on SDS-hydroxylapatite columns. The two major components (gC and gA/gB) were purified free of other polypeptides and used to prepare specific antisera to these glycoproteins. Radioimmune precipitation demonstrated that these antisera were specific for the antigens used in their production. These two antisera as well as an anti-VP123 serum were further characterized by immunoprecipitation, neutralization, and membrane immunofluorescence techniques. Results indicate that both of the major glycoprotein antigens are expressed on the surface of virions as well as on the surface of infected cells. PMID- 6252347 TI - Subgenomic fragment of molecular cloned Friend murine leukemia virus DNA contains the gene(s) responsible for Friend murine leukemia virus-induced disease. AB - Friend murine leukemia virus (G-MuLV) is a helper-independent, type C retrovirus isolated from stocks of Friend virus complex (spleen focus-forming virus plus MuLV). In cell culture, F-MuLV has an ecotropic and NB-tropic host range and causes XC cells to fuse. When injected into newborn NIH Swiss mice, F-MuLV produces hepatosplenomegaly, severe anemia, and numerous circulating hematopoietic precursors in the peripheral blood with normal thymus and lymph nodes after 3 to 6 weeks. Recently, we molecularly cloned an 8.5-kilobase pair (kbp) form of F-MuLV DNA from which we could recover the pathogenic F-MuLV virus by DNA transfection of NIH 3T3 cells. From this molecularly cloned F-MuLV DNA, we have now subcloned in pBR322 a 4.1-kbp HindIII fragment which contains in continuity 3.0 kbp from the 3' terminus (env and c region), 0.6 kbp of the terminal repeat sequences, and 0.5 kbp from the 5'terminus of the viral RNA (genome). NIH 3T3 fibroblasts were transfected with this DNA fragment an then infected with the wild mouse amphotropic retrovirus (cl 1504-A). In cell culture, 1504-A is a helper-independent type C virus which has an N-tropic host range and does not cause fusion of XC cells. When injected into newborn NIH Swiss mice, 1504-A does not produce splenomegaly or thymic enlargement in mice held for up to 8 months. The transfection with the F-MuLV fragment and the infection with 1504-A consistently yielded virus preparations that were XC positive. From such virus stocks we were able to isolate both helper-independent and replication-defective XC-positive viruses. The helper-independent virus was shown to be a recombinant virus since it contains a gp70 molecule derived at least in part from F-MuLV and a specific gag precursor derived from 1504-A as determined by radioactive immune precipitation assays. When injected into newborn Swiss mice, the recombinant helper-independent virus caused hepatosplenomegaly in approximately 50% of the mice in 6 to 8 weeks. The histology of the diseased splenic tissue was indistinguishable from that seen in the disease caused by the whole F-MuLV. The replication-defective virus could be pseudotyped with new 1504-A virus, and this viral complex also caused the F-MuLV disease picture when the complex was injected into newborn Swiss mice. We conclude that the genetic information responsible for the pathogenicity of F-MuLV is contained within the 4.1-kbp DNA fragment, which includes env gene sequences, the terminal repeat sequences, and the c region sequences of the F-MuLV genome. PMID- 6252349 TI - Characterization of the 5'-terminal cap structures of early simian virus 40 mRNA. AB - Early simian virus 40-specific mRNA was isolated from lytically infected and stably transformed cells and analyzed with respect to the 5'-terminal cap content. An analogous diversity of capped structures was found in both RNA preparations, indicating that 5'-terminal heterogeneity is not limited to late simian virus 40 RNA transcription but concerns a more general feature. Correlation of our data with previously published results of characterization of early mRNA's by reverse transcription allowed a tentative localization of the major 5' termini on the viral genome. PMID- 6252348 TI - Murine mammary tumor virus structural protein interactions: formation of oligomeric complexes with cleavable cross-linking agents. AB - Murine mammary tumor virus protein interactions in the intact virion structure were studied with the use of the cleavable cross-linking reagents dithiobis(succinimidyl propionate) and methyl 4-mercaptobutyrimidate hydrochloride. Cross-linked oligomeric complexes of murine mammary tumor virus proteins were analyzed by two-dimensional gel electrophoresis. Among the complexes most consistently formed were a heterodimer of the two glycoproteins gp36 and gp52, the homodimer of gp36, and the homotrimer of gp52. A very prominent oligomer formed at higher concentrations of dithiobis(succinimidyl propionate) was a complex of about 230,000 molecular weight, made up of three molecules each of gp36 and gp52. A number of lines of evidence, including electron microscopic analysis, suggest that the 230,000-molecular-weight complex actually represents the murine mammary tumor virus spike structure. Of the murine mammary tumor virus core proteins, p14 forms homooligomers most readily. Upon cross-linking with methyl 4-mercaptobutyrimidate hydrochloride a small amount of what seems to be a heterodimer made up of the N-terminal gag protein p10 and the hydrophobic membrane glycoprotein gp36 can be observed. PMID- 6252350 TI - Equine connective tissue tumors contain unintegrated bovine papilloma virus DNA. AB - Bovine papilloma virus (BPV) appears to be the etiological agent of common equine connective tissue tumors. We investigated the physical state of the viral DNA within such tumors and found no indication for integration into the host genome. The BPV genomes were present as free circular episomes. Two equine sarcoids were shown to contain multiple copies of free circular BPV type 1 (BPV-1) DNA. When the tumors were digested with several single-cut restriction enzymes, there were only form III BPV-1 DNA sequences could be revealed. One of the sarcoids contained, apart from wild-type BPV-1 DNA, a class of smaller BPV-1 circular DNA molecules bearing a deletion of approximately 9% of the BPV-1 genome. This deletion is located in the physical map between the relative units 0 and 0.32. PMID- 6252351 TI - DNA of avian myeloblastosis-associated virus type 2 integrates at multiple sites in the chicken genome. AB - The cellular sites of integration of the avian myeloblastosis-associated virus type 2 (MAV-2) DNA have been examined by Southern blot analysis of cellular DNA from infected cloned and uncloned chicken embryonic fibroblasts. Provirus-cell juncture fragments were not detected in restriction enzyme digests of DNA from MAV-2-infected uncloned cells. However, each MAV-2-infected cell clone examined produced a unique set of junctive bands. Thse findings indicate that multiple sites of integration exists for MAV-2 proviruses in cellular DNA. PMID- 6252353 TI - Recent advances in pediatric urological ultrasound. PMID- 6252352 TI - Transcription pattern of in vivo-labeled late simian virus 40 RNA: evidence that 16S and 19S mRNA's are derived from distinct precursor RNA populations. AB - The biosynthesis of the two major simian virus 40 mRNA molecules (19S mRNA and 16S mRNA) made at late times in the infective cycle was reinvestigated. By using a modified S1 nuclease technique, we were able to differentiate between pulse labeled RNA precursor and the spliced mRNA. During a 5-min pulse-labeling with [3H]uridine in vivo, only precursor RNA molecules were detected. Experimental results with polyadenylic acid-selected 5-min pulse-labeled RNA are consistent with the notion that simian virus 40 late RNA can be polyadenylated before final splicing. Finally, 19S mRNA was spliced much more rapidly and appeared more quickly in the cytoplasm than 16S mRNA. Nevertheless, approximately one-half the precursor molecules were destined to become 16S mRNA. Thus, for at least these two viral mRNA's derived from a common transcription unit, the rate of splicing and the rate of nuclear exist are not major determinants of relative mRNA abundance. PMID- 6252354 TI - Malignant fibrous histiocytoma of the spermatic cord. AB - We present 3 cases of malignant fibrous histiocytoma arising from the spermatic cord. This tumor occurs rarely in genitourinary organs and only 2 cases involving the spermatic cord have been reported previously. Recurrence rates of approximately 44 per cent of malignant fibrous histiocytoma in other sites are not improved by radiation or chemotherapy as adjuvants or primary means of treatment. Radical inguinal orchiectomy along with wide en bloc local resection is the therapy of choice. PMID- 6252355 TI - Association of immune responsiveness to cytomegalovirus infection with survival of renal allografts. AB - The association of immune responsiveness to cytomegalovirus infection was studied in relation to survival of renal allografts. The presence of anti-cytomegalovirus antibody in the pre-transplant patient was not associated with any detrimental effect on the graft survival. The presence or absence of cytomegalovirus antigen or of cytomegalovirus antibody, or later development of cytomegalovirus antibody, in no way affected the graft survival. The same conclusion was reached in cases when kidneys from male donors were used in cytomegalovirus antibody-postive patients. PMID- 6252356 TI - Cryptic pulmonary lesions in workers occupationally exposed to dust containing silica. AB - Fibrotic lesions associated with deposits of crystalline silica were found postmortem in the lungs of 15 granite workers who lacked radiological evidence of pneumoconiosis. All members of this occupational group had been employed in the granite quarrying and monument industry of Vermont since ambient air-dust standards were introduced in 1937. Although particulate silica was not revealed in the lesions by traditional polarization light microscopy, it was identified by scanning electron microscopy in conjunction with backscatter imaging and x-ray spectrometry. The etiologic basis of the fibrotic pulmonary disease would not have been diagnosed without the aid of these modern analytical tools. Exposure to silica-containing dust can result in cryptic pulmonary disease that is not detectable radiologically. In these retrospective postmortem studies, it was not possible to define the distribution of the lesions in the lungs. PMID- 6252357 TI - Smoking abstinence and small cell lung cancer survival. An association. AB - The prognostic implications of cigarette smoking were investigated in 112 patients with small cell lung cancer. Twenty had stopped smoking permanently before diagnosis (NS-Prior), 35 had stopped at diagnosis (NS-Dx), and 57 patients continued smoking (S). Therapies included chemotherapy alone or with radiation therapy, with or without thymosin fraction V. The survival difference among the three groups was statistically significant. The NS-Prior patients had the best survival, followed by NS-Dx patients and finally S patients. No S patient has survived, disease free, more than 96 weeks, while three NS-Prior and three NS-Dx patients are disease free 103 to 220 weeks after start of treatment. Thymosin, 60 mg/sq m, yielded survival benefits for the S group only. Continuation of smoking during the treatment of small cell lung cancer was associated with a poor prognosis, while discontinuation of smoking, even at diagnosis, may have beneficial effects on survival. PMID- 6252358 TI - Pork tapeworm of Cysticercus involving peripheral nerve. PMID- 6252359 TI - [A case of Chediak-Higashi syndrome (author's transl)]. PMID- 6252361 TI - [Small cell carcinoma of the lung (author's transl)]. PMID- 6252360 TI - [Disappearance of the right paratracheal stripe and its diagnostic significance (author's transl)]. PMID- 6252362 TI - Short gastric veins as the major portal of entry for milk-borne murine mammary tumor virus. AB - The flow pattern of the short gastric veins that drain the fundic portion of the stomach appeared to influence mammary tumorigenesis. In I and C57BL mice, strains that are highly resistant to murine mammary tumor virus (MuMTV)-induced mammary tumorigenesis, the short gastric veins empty directly into the splenic vein outside the spleen, connecting with the portal system. In (C57BL X I)F1 mice, which are highly susceptible to MuMTV-induced mammary tumorigenesis, the short gastric veins empty directly into the superior hilus of the spleen, connecting with the splenic parenchyma. Neonatal splenectomy or cauterization of the short gastric veins of (C57BL X I)F1 mice prior to the introduction of MuMTV by foster nursing delayed the onset and reduced the final incidence of mammary tumors. When neonatal splenectomy was performed after milk-borne MuMTV introduction, it caused premature appearance of mammary tumors without affecting the final tumor incidence. In A, BALB/c, C3H, DBA/2, GR, and RIII mice, strains that are susceptible to MuMTV-induced mammary tumorigenesis, the short gastric veins also empty into the superior hilus of the spleen. Our findings suggest that susceptibility to mammary taumorigenesis may depend on the direct entry of milk borne MuMTV into the splenic environment through the short gastric veins that drain the fundus of the stomach. PMID- 6252363 TI - Carcinogenicity of 2,2'-dihydroxy-di-n-propylnitrosamine in the tree shrew (Tupaia glis): light and electron microscopic features of pulmonary adenomas. AB - The carcinogenic effect of 2,2'-dihydroxy-di-n-propylnitrosamine (DHPN) was examined in the primitive primate, tree shrew (Tupaia glis). DHPN was administered at a dose of 250 mg/kg body weight sc once a week for 80 weeks. Between 65 and 102 weeks, 8 of 9 males given DHPN (89%) and 11 of 14 females given DHPN (78%) developed pulmonary adenomas. In 2 DHPN-treated males, in addition to adenomas, bronchioalveolar carcinomas were observed. Transmission electron microscopic examination of pulmonary adenomas from 4 DHPN-treated animals showed that Clara cells were the main components of these tumors. In addition to pulmonary tumors, 9% of the DHPN-treated animals developed squamous cell carcinomas of the skin and hepatocellular carcinomas. None of the 6 controls, which received olive oil alone, developed any tumors. PMID- 6252364 TI - Murine leukemia viruses: induction of macrophage production of granulocyte macrophage colony-stimulating factor in vitro. AB - Infection in vitro of freshly explanted N:NIH(S) mouse bone marrow with ectopic murine leukemia viruses produced an increase over control uninfected cultures in the 50 or more cell granulocyte-macrophage (GM) colonies and 10-49 cell clusters detected after 7 days of incubation in 0.3% agar at 37 degrees C and 7% CO2. This effect was observed only at plating densities above 5.0 X 10(4) cells/ml and was not observed with macrophage-depleted populations of colony-forming units of GM progenitor cells (GM-CFUc) purified by isopyknic density gradient centrifugation of nonadherent cells harvested from long-term bone marrow cultures. Fewer virus infected, compared to uninfected, peritoneal exudate macrophages were required to stimulate the same number of GM colonies and clusters in a given number of purified GM-CFUc. In contrast, murine leukemia virus infection of T-lymphocytes or NIH/3T3 embryo fibroblasts did not stimulate release of GM-CFUc coloney stimulating factor (CSF). Single Cell suspensions of virus-infected freshly explanted whole bone marrow grown in CSF concentrated from L929 or WEHI-3 cell conditioned medium produced more GM-CFUc colonies and GM clusters/1 X 10(5) cells compared to single cell suspensions of uninfected marrow. This phenomenon suggests that the colonoy-forming cells responding to CSF from virus-infected marrow may have been different from those responding to L929 or WEHI-3 cell CSF. The data indicate that increased granulopoiesis observed following retrovirus infection in vivo or in long-term marrow cultures was attributable in part to virus stimulation of production of CSF by adherent marrow stromal cells including macrophages. PMID- 6252365 TI - [Phosphodiesterase characteristics of the fat cells in spontaneous hypertension in rats]. AB - The activity of cAMP and cGMP phosphodiesterases in the cytosol and endoplasmic reticulum fraction of rat adipocytes was studied in animals of 4 groups: intact and adrenalectomized rats with normal pressure, intact and adrenalectmized rats with spontaneous genetic hypertension. It is shown that in animals of all groups the rate of cGMP hydrolysis in these fractions is higher than the rate of cAMP hydrolysis and that 90% of the activity of the enzymes that were studied occurs in the cytosol. Determination of the dependence of phosphodiesterase activity of cyclic nucleoides on a substrate concentration of 10(-8) to 10(-4) M made it possible to estimate the values of Hill's coefficients characterizing the degree of co-operation of the noted reactions. Increased activity of cAMP phosphodiesterase with low and high Km value and increased activity of cGMP enzyme were revealed in the cytosol of fat cells in rats with normal pressure after removal of the adrenals; the activity of these enzymes in the endoplasmic reticulum fraction did not change after adrenalectomy. In rats with spontaneous genetic hypertension the activity of both forms of cAMP and cGMP enzymes in the adipocyte cytosol increased after removal of the adrenals; in the microsome fraction the activity of cAMP phosphodiesterase with low Km value was reduced whereas the activity of cAMP phosphodiesterase with high Km value and the activity of cGMP in the region of high substrate concentration were increased. PMID- 6252366 TI - [Results of treatment of Wilms' tumors according to a plan (I/76) of the Society of Pediatric Oncology--a retrospective analysis (author's transl)]. AB - A new treatment protocol for the treatment of Wilms' tumors was proposed in 1976 by members of the German Society for Pediatric Oncology (Gesellschaft fur Padiatriche Onkologie e.V.). The data collected in 2 1/2 years (until June, 1979) and concerning 48 children, are presented in this retrospective analysis. The results of treatment in 34 children are discussed. Considerations are made for an actualized national treatment protocol for Wilms' tumors in the Federal Republic of Germany. PMID- 6252367 TI - [Ultrasonic examinations of Wilms' tumors stage II-V during preoperative therapy (author's transl)]. AB - Ultrasonic examinations were performed at weekly intervals in 8 patients with Wilms tumors Stage II-V during the period of preoperative therapy. Measurements of the maximum expansion of the tumors were made and expressed in an ellipsoid formula. The tumor volume was thus calculated. A description of the compactness of the tumor as well as the bordering of the tumor were done. This was followed by a photographic documentation. The mean value of the initial tumor volume in the 8 patients was 551 ml. At the end of the preoperative therapy, an average volume of 305,1 ml was recorded. One week after beginning the therapy, 25-40% diminution of the initial tumor volume was noted in 5 patients. The diminution in volume till tumor extirpation was in all 49%. In 3 patients, the reduction of tumor mass through therapy was only 27,8%. The histological examinations revealed a fetal rhabdomyomatic nephroblastoma in one case. The second case was massive tumor haemorrhage and in the third case a considerable formation of cysts. PMID- 6252368 TI - [Matrix activity of chromatin DNA and the adenylate cyclase system in the tissues of rats after a flight aboard biosatellite "Cosmos-936"]. AB - Chromatin DNA template activity and cAMP metabolism enzymes in the liver and lymph organs of rats flown for 19 days were studied. Postflight RNA synthesis on the chromatin DNA template was increased in the liver and decreased in lymph organs. Adenylate cyclase and phosphodiesterase activities decreased in the liver and increased in lymph organs. No correlation between cAMP enzyme activity and chromatin DNA template activity was found. The nature of the biochemical changes in animal tissues is discussed. PMID- 6252369 TI - Failure of heart rate response to cardioaccelerator nerve stimulation in Siamese cats. AB - Heart rate responses during stimulation of the cardioaccelerator nerves were compared using Siamese and non-Siamese cats. The positive chronotropic responses of Siamese cats during activation of the cardioaccelerator nerves were significantly less than that observed for non-Siamese cats. There were no differences between the two cat populations when vasopressor and chronotropic responses to norepinephrine were cmpared. Comparison of atria from Siamese and non-Siamese cats using histochemical fluorescence indciated that there was a decreased norepinephrine content of the sympathetic nerves innervating the atria of Siamese cats. PMID- 6252370 TI - Nerve growth factor-induced neurite outgrowth from normal human chromaffin cells. PMID- 6252371 TI - The effect of collagenase on the formation of fibrous long spacing collagen aggregates. AB - In order to elucidate the close relationship between the formation of fibrous long spacing fibers (FLS) and collagenase activity, electron microscopic studies on the rat skin using tissue culture technique were performed. In culture of newborn rat skin, a large number of FLS was formed in the dermis in which activity of endogenous collagenase was markedly elevated. Ethylenediaminetetraacetic acid (EDTA) supplemented to the culture medium completely arrested the formation of the FLS; subsequent exposure to bacterial collagenase resulted in the appearance of FLS in the same fashion. In another set of experiments utilizing exogenous enzyme digestion with bacterial collagenase or chondroitinase ABC on skins of 1-day-old and 1-year-old rats, it was demonstrated that the FLS formed by incubation with bacterial collagenase were found only in the regions of the dermis where reticular fibers were identified by light microscopy. There was no effect of chondroitinase ABC on FLS formation. These studies indicate that the FLS are formed in the presence of elevated endogenous collagenase and might be derived from reticular fibers which are degraded by collagenase. PMID- 6252372 TI - Spongiform polioencephalomyelopathy caused by a murine retrovirus. I. Pathogenesis of infection in newborn mice. PMID- 6252373 TI - Sampling procedures for blood delta 1-tetrahydrocannabinol analysis and interference by antioxidant. PMID- 6252374 TI - A rapid microassay for myocardial ATPases. PMID- 6252375 TI - The neomucosa and its surroundings after jejunoserosal patching in dogs. PMID- 6252376 TI - Central control of hepatic steroid metabolism and "lactogenic" receptor. PMID- 6252378 TI - Regulation of steroidogenesis in the human placenta. PMID- 6252377 TI - The ether-catalyzed dissociation rate of estradiol-receptor complex distinguishes between hormone-sensitive and resistant rat mammary tumors. PMID- 6252379 TI - The isolation and characterization of the chicken lysozyme and ovomucoid gene. PMID- 6252380 TI - Mechanisms implicated in ACTH-induced steroidogenic and DNA synthesis refractoriness on adrenal mouse cell line (Y-1). PMID- 6252381 TI - Hormonal modulation of protein degradation in Y-1 adrenal cells. PMID- 6252382 TI - Recent views on endocrine effects of catecholestrogens. PMID- 6252383 TI - A comparative study of the role of vasopressin and ACTH in the regulation of growth and function of rat adrenal glands. PMID- 6252384 TI - Adrenal desensitization following prolonged ACTH administration to normal subjects. PMID- 6252385 TI - Development and characterization of a radioimmunoassay technique for aldosterone. Application to the study of aldosterone output from perifused frog interrenal tissue. PMID- 6252386 TI - Urinary metabolites of vitamin D3. PMID- 6252387 TI - ACTH peptides and the development of the fetal adrenal. PMID- 6252388 TI - A new procedure for the formation of isotachysterol derivatives of subnanomole quantities of ergocalciferol, cholecalciferol and its metabolites prior to gas liquid chromatography. PMID- 6252389 TI - Effect of cortisol, T3 and T4, on the glucocorticoid receptor concentration in leukocytes. PMID- 6252390 TI - A comparative study of breast cancer in the black and white populations of two inner-city hospitals. AB - A comparative study of breast cancer was made among black and white populations admitted to two inner-city hospitals from 1971 through 1976, inclusive. There were 306 patients in the study group of which 162 were black and 144 were white. Age, sex, color, duration of illness, different quadrants of breast involved, staging of cancer, histological diagnosis, treatment given, and incidence of recurrence were studied in each group. A statistically higher incidence of cancer of the breast was found among the black patients in the groups aged 30--50 years and 70--80 years, as compared to the white population. All other parametes studied showed no statistical differences. PMID- 6252391 TI - Ultrastructural study of myoepithelial cells in breast carcinoma. AB - This investigation was designed to study the myoepithelium of the human mammary carcinoma. Tissues were obtained from 30 infiltrating ductal carcinomas. Under light microscope, there were no significant changes noted in the myoepithelium. Glutaraldehyde-fixed tissues were examined under electon microscope. In infiltrating carcinoma the myoepithelial cells contained increased endoplasmic reticulum, abundant microfilaments, secretory granules and intracytoplasmic duct formation. This observation suggests that myoepithelium takes an important and active role in the infiltrating stage of the human mammary carcinoma. PMID- 6252392 TI - The relationship of dietary selenium and breast cancer. AB - An inverse relationship exists between dietary selenium (Se) concentrations and the incidence of human breast cancer. The addition of Se to the diet has been shown to decrease the incidence of spontaneous murine mammary tumors. We compared the serum Se concentrations in breast cancer patients with those of women without breast cancer. Serum was collected from 35 women with breast cancer. Nineteen of these women had infiltrating ductal carcinoma and two had Paget disease of the nipple. Nine women had lymph nodal metastases at the time of mastectomy, four had definite evidence of metastatic disease when the blood samples were drawn, and the disease process of one patient was unclassified. Samples from 27 women known to be free of breast cancer were used as controls. The difference noted between the mean serum Se concentrations of breast cancer patients and controls were found to be significant. PMID- 6252393 TI - Diagnosis of hepatoma by scintigraphy using multiple radionuclides. AB - The conventional liver scan, using 99mTC-sulfur colloid, is very sensitive in detecting focal abnormalities, but it is nonspecific, since most lesions appear as "cold" defects. Liver scan can be much more specific if the right combination of the many available radiopharmaceuticals is used. This fact is exemmlified by our case report of hepatoma. All scans can be done noninvasively, with low radiation exposure to the patients. PMID- 6252394 TI - Influence of age on 5'-nucleotidase in plasma membranes isolated from rat liver. AB - Studies were carried out to determine the kinetic properties of 5'-nucleotidase from liver plasma membranes in rats of different ages; four groups were examined, namely rats 25 +/- 2, 60 +/- 5, 230 +/- 15 and 525 +/- 20 days old. The 5' nucleotidase showed minimum Vmax values in young rats; differences in this kinetic parameter were not detected among the other groups. However, the Km values increased during growth and development, declined in young animals and increased again in the middle-aged. Arrhenius plots of the 5'-nucleotidase activity showed a single break at aroung 22 degrees C in developing the middle aged animals; the break temperature decreased to 17 degrees C in the rats 230 +/- 15 days old. The pH-Vmax and pH-Km curves showed a maximum at pH 7.6 at all ages. Lipid analysis of membrane preparations was carried out. Phospholipid composition did not change markedly with age. The cholesterol level decreased between 25 +/- 2 and 60 +/- 5 days. The degree of saturation of fatty acids seemed to increase in the same period, but reached the lowest value in the young rats. The results indicate that either sphingomyelin or other phospholipids do not affect the isothermal kinetics of 5'-nucleotidase during development and aging. Furthermore, phospholipid polar groups as well as the cholesterol and fatty acids of the bulk lipid phase modulate the membrane fluidity in the same way at different ages. Finally, the modifications of the Km with age cannot be correlated with changes in the surface charge. PMID- 6252395 TI - [Carcinoid tumor of the thymus gland with multiple metastases. Report of a case (author's transl)]. AB - A pregnant woman in the 29th, week of gestation was admitted to the hospital with mediastinal pressure symptoms. A tentative diagnosis of lymphoma was made and the patient was given chemotherapy (vincristine, ciclophosphamide and adriamycin) plus radiotherapy, but no objective response was obtained. During the postoperative period (cesarean section) the patient developed clinical symptoms of muscular paralysis of unknown etiopathogenesis. Biopsy of a cervical lymph node showed histological pattern of tumor of the APUD system (chemodectoma). Multiple metastases appeared in the lungs, bones, brain, heart and ovaries in spite of treatment with various chemotherapeutic agents (vincristine, actinomycin D, CCNU and DTIC). Necropsy revealed the existence of a large tumor of the thymus gland, which histopathologic structure resembles to that of carcinoid. Ultrastructural examination showed abundant granules of neurosecretion confirming an APUD tumor. Cushing-like appearance of the patient was attributed "a posterior" to ACTH released by the tumor. A review ofthe clinical features, endocrine function and anatomical localizations of carcinoid tumors is included. PMID- 6252396 TI - Glomus vagale. AB - Glomus tumors of chemodectomas are unusual neoplasms of the head and neck. They are more prevalent in the jugular foramen and in the middle ear. Glomus vagale is very rare. To date, there are about 70 cases reported in the literature. Only two of the cases described occurred bilaterally. Two cases are reported here; one was diagnosed as having a bilateral glomus vagale. Radiation therapy was used in the treatment of one side in order to avoid bilateral vagus nerve damage. The incidence, diagnosis and management of glomus vagale tumors are discussed. PMID- 6252397 TI - Fibrous histiocytoma of the nasal cavity. AB - The case of a 17-year-old female patient with a polypoid tumor in the right nasal fossa, diagnosed as fibrous histiocytoma and treated by polypectomy and maxillectomy, is reported. It represents a very unusual variety of nasal neoplasm, generally of unpredictable course. The clinical and morphological characteristics of seven previously published additional cases are also reviewed. PMID- 6252398 TI - Small cell anaplastic carcinoma of the larynx: review of the literature and report of a case. AB - The case study of a patient with small cell anaplastic carcinoma (oat cell) of the larynx is detailed and the literature is reviewed. Small cell anaplastic carcinoma of the larynx has been demonstrated to be histologically identical to small cell anaplastic carcinoma of bronchogenic origin. The aggressive biologic behavior of this tumor justifies managing small cell anaplastic carcinoma as a systemic disease. Because of early widespread dissemination of tumor, surgery or radiotherapy alone or in combination have not been successful in controlling the disease. The combination of radiotherapy with chemotherapy has been shown to be the most effective approach to the treatment of small cell anaplastic carcinoma of the lung. We believe that a similar regimen should be considered the treatment of choice for small cell anaplastic carcinoma of the larynx. PMID- 6252399 TI - Marihuana: a forensic problem. AB - Early and unfounded stories concerning marihuana led to many sanctions being placed on the drug. They have also brought about the requirement that the drug be proved safe beyond any reasonable doubt for any consideration to be given to removing restrictive sanctions. Some of the misinformation has been dispelled by controlled studies of its effects. Present available research does not support the thesis of permanent damage, either physical or mental. Yet there appears to be no ongoing research that will adequately demonstrate the safety or the dangers of the drug. PMID- 6252400 TI - Opioid peptides in adrenal gland. PMID- 6252401 TI - Effects of alpha 2-adrenergic action on cyclic AMP levels in canine thyroid slices. PMID- 6252402 TI - Reduction of food intake by piribedil in the rat: relation to dopamine receptor stimulation. PMID- 6252403 TI - Striatal opiate receptors: pre- and postsynaptic localization. PMID- 6252404 TI - Developmental differences between high and low affinity opiate binding sites: their relationship to analgesia and respiratory depression. PMID- 6252405 TI - Simultaneous inhibition of guinea pig brain 2',3'-cyclic nucleotide 3' phosphohydrolase and myelin protein synthesis by 2'-adenosine monophosphate. PMID- 6252406 TI - Evidence for a membrane surface defect in erythrocytes in Huntington's disease. PMID- 6252407 TI - [Stopping powers of materials for heterogeneous skull phantoms]. PMID- 6252408 TI - [Clinical and experimental evaluation of osteotropic radiopharmaceutical preparations]. PMID- 6252409 TI - [Combined protection of the body during irradiation]. PMID- 6252410 TI - [Use of narrow proton beams for treating eye tumors]. PMID- 6252411 TI - [Selection of priorities in public health (author's transl)]. AB - Identification of priorities is a major factor in an public health programme. We should avoid making a selection of priorities on a subjective basis, or basing a decision on temporary situations or the desire of influential personalities confusing personal interests with true priorities. The choice of priorities in health care must take into account two essential factors: 1) The impact of a disease on the population. It can be evaluated by studying:--the mortality rate and the increased life expectation resulting from the suppression of the disease; -the incidence of the disease;--the temporary or the permanent disablement it causes;--the incidence of complications. 2) The possibility of success of health programmes. The possibility of success depends on many factors: technical, logistic, political and psychological, which should be analysed in depth before establishing any priority programme. A public health programme can only be given priority rating when it combines maximum impact on the population with the highest chance of success. Priority rating can be attributed to a public health programme only when long term impact on the population and successful achievement can be combined. PMID- 6252412 TI - [Clinical experiences with cefotaxim]. PMID- 6252413 TI - [Hepatocellular carcinoma following oxymetholone treatment]. PMID- 6252414 TI - [The problem of outsider methods in medicine (II)]. PMID- 6252415 TI - [Kinetics of bactericidial function of cefotaxim against Pseudomonas aeruginosa alone and in combination with tobramycin]. PMID- 6252416 TI - Use of glutaraldehyde as a coupling agent for proteins and peptides. PMID- 6252417 TI - Electrode-Based Enzyme Immunoassays usings urease conjugates. PMID- 6252418 TI - Interactions among retroviruses Mason-Pfizer monkey, baboon endogenous, simian sarcoma virus-associated and murine leukemia detected by virus-mediated cell fusion inhibition assay. PMID- 6252419 TI - Induction of a stable phagocytic property by cytosine arabinoside in an SV40 transformed macrophage cell line. PMID- 6252420 TI - Cushing's disease with hyperprolactinaemia treated by transsphenoidal hypophysectomy. AB - A case of Cushing's disease and hyperprolactinaemia is reported. The two endocrinological abnormalities could be suppressed independently of one another, and both were apparently relieved by transsphenoidal hypophysectomy. PMID- 6252421 TI - Diet in the treatment of diabetes. PMID- 6252422 TI - Rotavirus infection in young children in the highlands of Papua New Guinea. AB - Rotavirus infections were detected by electron microscopy examinations in 54 of 66 children (82%) with acute gastroenteritis which necessitated admission to hospital during April to July, 1979, in the Highlands of Papua New Guinea. Longitudinal epidemiological studies may confirm rotavirus infections to be more important aetiolgical agents of childhood gastroenteritis in this region than in many other countries studied to date. PMID- 6252423 TI - Herpes virus in an obstetric hospital. III: Prevalence of antibodies in patients and staff. AB - Seventy per cent of 890 patients and staff members of an obstetric hospital tested for complement-fixing serum antibodies to herpes simplex virus (HSV) were found to be seropositive. Employment, age, socioeconomic and ethnic factors of patients and different categories of staff members were examined in relation to the prevalence of HSV antibodies. Significant differences in the prevalence of antibodies were found between these groups. PMID- 6252424 TI - Pregnancies using conjugated oestrogen therapy. PMID- 6252426 TI - [Which factors influence skeletal metastases of breast cancer?]. PMID- 6252425 TI - Aspects of the pharmacology of prazosin. PMID- 6252427 TI - [Genesis of breast cancer: a multifactorial etiology]. PMID- 6252429 TI - [Comparative characteristics of reproduction of Getah and West Nile viruses in cell cultures of mosquitoes of 3 species]. PMID- 6252428 TI - Long-term survivors of high-grade malignant astrocytomas. AB - This report descibes our experience with 40 evaluable patients with high-grade malignant astrocytomas. Eleven patients were treated with surgery and radiotherapy; 29 patients were treated with surgery, radiotherapy, and BCNU chemotherapy. Ten of these 29 patients are two-year survivors. Their mean survival is over 57.3 months, and they have been off chemotherapy for one to 27 months, mean 13.7 months. Seven of these patients received 800 to 1,100 mg/m2 of BCNU; three other long survivors received greater amounts of BCNU. Our current recommendation is that patients with high-grade malignant astrocytomas be treated with surgery, radiotherapy, and at least 800 mg/m2 of BCNU. PMID- 6252430 TI - Conceptual design of beryllium targets for the generation of neutron beams for radiation therapy by the (p,n) reaction. AB - A conceptual design is presented showing that, by judiciously choosing the beryllium target thickness and the backstop material, improvements can be achieved in dose-rate, skin sparing, and penetration of neutron beams generated by the same proton accelerator. PMID- 6252431 TI - The influence of target thickness and backstop material on proton-produced neutron beams for radiotherapy. AB - Results are presented of measurements of skin sparing, penetration and total dose per unit of incident charge for various target thicknesses and filtrations for a neutron beam generated by 42 MeV protons on beryllium. These results are contrasted to predictions outlined in a previous paper. The differences from these predictions are attributed to the contribution of low-energy neutrons produced by the residual proton beam in the thick copper target backstop. PMID- 6252432 TI - An intercomparison of neutron measurments for a 25 MV x-ray radiotherapy accelerator. AB - High-energy x-ray radiotherapy machines produce neutrons by photonuclear reactions which present a potential radiation hazard to the personnel and patient. A series of measurements of the neutron flux from a 25 MV x-ray linear accelerator, inside and outside the treatment room, have been performed using a multisphere spectrometer, Nemo dosimeter, and activation detectors. These results are compared with other mixed photon-neutron field measurements for the same machine performed using an argon/propane ionization chamber, silicon diode, track etching detectors, and Monte Carlo calculations. It is found that these measurements agree with each other within a factor of two except for silicon diode measurements in the photon beam. Measured neutron spectra at various locations in the treatment room are also compared with the results of Monte Carlo transport calculations. PMID- 6252435 TI - An unusual case of hypoadrenocorticism in a dog. PMID- 6252434 TI - Viruses of guinea pigs: considerations for biomedical research. PMID- 6252436 TI - Sites of action of phencyclidine. II. Interaction with the ionic channel of the nicotinic receptor. PMID- 6252437 TI - Alterations in cardiac autonomic receptors following 6-hydroxydopamine treatment in rats. PMID- 6252438 TI - beta-Adrenergic-sensitive adenylate cyclase in choroid plexus: properties and cellular localization. PMID- 6252439 TI - Affinity labeling of angiotensin II receptors in the isolated rat uterus with a photolabile antagonist. PMID- 6252440 TI - Effects of sodium iodide, lithium bromide, and deoxycholate on dissociation of [3H]ouabain-Na,K-ATPase complex during enzyme isolation. PMID- 6252433 TI - Clostridium botulinum neurotoxin. PMID- 6252441 TI - Lipid-protein interactions in the multiple forms of monoamine oxidases: lipases as probes using purified intact rat brain mitochondria. PMID- 6252442 TI - [Conformational stability of glutamate dehydrogenase and its complexes with specific ligands]. AB - The isotermic denaturation of glutamatdehydrogenase (GDH) and its complexes with co-enzymes, substrates and allosteric regulators under the action of urea was studied. It was shown that the reaction of the enzyme with an allosteric inhibitor GTP is accompanied by a decrease in conformational stability of the catalytically active hexsamer GDH. Formation of a complex with the allosteric activator ADP increases the conformational stability of the enzyme. Studies on the isotermic unfolding of GDH in the presence of various phosphoric ethers of adenosine gave evidence that the stabilizing effect of ADP is based on the reaction of the enzyme with the adenine base of the regulator. PMID- 6252444 TI - [Phosphorylation of endogenous proteins of bovine retina rod outer segments]. AB - The components of bovine rod outer segments (ROS) and water-soluble extracts of ROS were separated by SDS-electrophoresis after incubation with [gamma-32P]ATP or [gamma-32P]GTP at different experimental conditions. After that gels were autoradiographed to reveal the phosphorylated intermediates. Our results suggest, that ROS contains the following protein kinase systems: 1) water-soluble cAMP dependent protein kinases, that uses ATP, but not GTP, and phosphorylates the water-soluble 30 000 molecular weight protein; 2) protein kinase that uses GTP (probably, ATP also) and phosphorylates the 20 000 molecular weight protein in light-adapted ROS; 3) water-soluble cyclic nucleotide- and Ca2+-independent protein kinase that uses ATP rather than GTP and phosphorylates the water-soluble 70 000 molecular weight protein. The concentrations of phosphorylated intermediates in bovine ROS are estimated. PMID- 6252443 TI - [Protein kinase activity of bovine retina rod outer segments]. AB - Dark-adapted pure bovine rod outer segments (ROS) (A280/A500--2.1) can be phosphorylated in the presence of [gamma-32P]ATP and [gamma-32P]GTP. The constant levels of phosphorylation, reached within 10--15 min, are 100 +/- 30 pmol 32P/nmol of rhodopsin for [gamma-32P]ATP and 2--4 pmol 32P/nmol of rhodopsin for [gamma-32P]GTP. These processes are not controlled by 10(-4)--10(-8) cAMP, cGMP or Ca2+, but are inhibited at higher concentrations of these agents. In the presence of histone the constant level of phosphorylation is increased up to 200 +/- 30 pmol 32P/nmol of rhodopsin for [gamma-32P]ATP, but is not changed when [gamma-32P]GTP is used. 10(-5) M cAMP is found to activate the phosphorylation in the presence of histone and [gamma-32P]ATP by 5--6 times. All this evidences that ROS contains cAMP-dependent protein kinase, which utilizes ATP, but not GTP. Moreover, ROS contains cyclic nucleotides- and Ca2+-independent protein kinase. These protein kinases are the ROS endogenous enzymes. This is shown in experiments on separation of pure ROS in a sucrose density gradient. PMID- 6252445 TI - [Determination of the secondary structure of proteins from their circular dichroism spectra. II. Estimation of the contribution of beta-pleated sheets]. AB - Protein-derived basic CD spectra for alpha-helical, beta-structural, beta-bends and irregular regions of the proteins have been determined from the experimental CD spectra of five reference proteins (myoglobin, lysozyme, ribonuclease A, papain, lactate dehydrogenase) with the knowledge of the fractions of the residues in the corresponding conformation. The alpha-helical and beta-structural regions of the reference proteins have been isolated from the X-ray data using the common "rigid" criteria for all the proteins, as proposed by Finkelstein and Ptitsyn. The residues in the beta-bend have been isolated using the data of Chou and Fasman and also three assumptions formulated in the present paper. The basic CD spectra thus obtained have been used for the analysis of secondary structures of 10 proteins (5 reference and 5 additional ones). There is a good agreement between the results of the X-ray data and those obtained from the CD spectra. PMID- 6252446 TI - [Physical mapping of Streptomyces coelicolor A3(2) actinophage DNA. II. Transposon-like structure in DNA molecules of phiC43 phage DNA, localization of region responsible for establishment of the lysogenic state]. AB - Structural properties of DNA molecules of phages phi C43, phi C43del and mutant phage phi C311yg33 were studied. Actinophages phi C43del and phi C311yg33 have been isolated and shown to have a phenotype characteristic of phages defective in integration, i. e. turbid plaques and inability to establish the lysogenic state. By means of heteroduplexing, deletions were mapped in the genomes of these phages. DNA molecules of phi C43del and phi C11yg33 are devoid of the common fragment, which suggests that the mutant phenotypic character is associated with structural alterations in DNA molecules. The presence of transposon-like structure in phi C43 DNA molecules has been inferred from the analysis of phi C43/phi C43del heteroduplexes and phi C43 homoduplexes. Also, a deletion in phi C43 genome has been detected covering the same region where deletions in phi C43del and phi C11yg33 DNAs were located. PMID- 6252447 TI - [Plasmids of Bacillus thuringiensis var. galleriae strain 612]. AB - We studied Bacillus thuringiensis var galleriae, strain 612 plasmids. B. thuringiensis cells contain double-stranded plasmid DNA molecules (ranging of about 12% from total DNA content) with buoyant density 1.59 g/cm3. Plasmid DNA content was constant during the exponential and stationary phases of bacterial growth. The plasmid fractions consist of DNA molecules with molecular weights of 5.9 x 10(6), 10.0 x 10(6), and 110.9 x 10(6) daltons (pVD1, pVD2 pVD3, respectively). Endonuclease EcoRI cuts the plasmids pVD2 and pVD3 into two and four fragments, respectivelyy, but pVDI seemed to be resistent to EcoRI treatment. We found that pVD2 and pVD3 plasmids contain a common DNA fragment with the molecular weight of 6.7 x 10(6) dalton as it was shown by restriction analysis. In contrast, the same plasmids contain the common fragment with molecular weight of 7.5 x 10(6) dalton as shown by heteroduplex analysis. Plasmid pVD3 has a transposon-like structure. PMID- 6252448 TI - [Electron paramagnetic study of electron transport in photosynthetic systems. X. Effect of magnesium ions on the structural state of thylakoid membranes and the kinetics of electron transport between the two photosystems in bean chloroplasts]. AB - The effect of Mg2+-ions on the physical state of thylakoid membrane and kinetics of electron transport between two photosystems were studied. The rate of electron transport from photosystem 2 to P700+ and the activity of photosystem 2 were obtained from the kinetics of P700 redox transients induced by flashes of white light (t1/2 = 7 musec or 0.75 msec) fired simultaneously with the background continuous far-red light (707 nm). The spin-labeled stearic acids (I1.14 and I12.3) were used as indicators of Mg2+-induced structural changes. Addition of MgCl2 stimulates incorporation of spin-labels into the lipid region of the thylakoid membrane. It was found that Mg2+-ions modify the ESR spectrum of I12.3. The results evidence that the screening of charged groups on the thylakoid membrane surface induces structural changes in the lipid region of the membrane. We have concluded that these structural changes result in reorientation of lipid molecules in the thylakoid membrane. There is a correlation between Mg2+-induced structural changes and electron transport in chloroplasts. Addition of Mg2+-ions stimulates the photochemical activity of photosystem 2 by increasing the amount of active reaction centres and modifies the rate constant of electron transport from photosystem 2 to P700+. It has been demonstrated that ion regulation of electron transport in more effective in the oxidising side than in the reducing side of plastoquinone shuttle. PMID- 6252449 TI - [Simple method of cloning eukaryote DNA: production of certain new ribosomal genes of Drosophila]. AB - We propose a simple method which allows to receive a collection of clones containing recombinant plasmids. It is based on the ligation of the longer fragment of pBR332 formed by EcoRI and BamH1 with eukaryotic DNA (from Drosophila melanogaster embryo in this case) partially cleaved with EcoRI and BamHI. This approach gave us 10(4) colonies from 1 microgram of Drosophila DNA and 0.1 microgram of the BamHI--EcoRI "vector". About 0.5% of all clones carried the fragments of ribosomal genes with insertions in the 26S gene. Ribosomal genes lacking insertions did not enter the collection due to some peculiarities in their restriction map. The sites of cleavage are mapped in eight recombinant plasmide for HindIII, BamHI and EcoRI. These maps show that some insertions within 26S gene have not been cloned earlier. The mean length of cloned fragments is 11.8 kilobases, the mean number of EcoRI and BamHI restriction sites are 1.2 and 1.0, respectively. The electrophoretical screening of plasmids using cetyl trimethyl ammonium bromide was developed. PMID- 6252450 TI - [Physical mapping of Streptomyces coelicolar A3(3) actinophages. III. Restriction analysis]. AB - It has been shown that endonucleases HindII, HindIII, SalI and BsuI treatment of phiC62, or phiC43 and phiC31 DNAs forms more than 20 fragments. EcoRI cleaves phiC62, phiC31, phiC31c5 and phiC31c28 into seven fragments, but phiC311yg33 into six fragments. Comparison of molecular weights of DNA restricts obtained after hydrolysis of phage DNAs containing deletions by endonuclease EcoRI made it possible to determine the location of four fragments on restriction map and to orientate this map in relation to the molecule's ends. BamHI cleaves phiC43 DNA into two fragments. By heteroduplexing BamHi site was mapped within the phiC43 insertion sequence. PMID- 6252451 TI - [Tumors caused by viruses]. PMID- 6252452 TI - [Clinical aspects of chronic virus infections]. PMID- 6252453 TI - [Recent aspects in diagnosis of hepatitis]. PMID- 6252454 TI - [Results of precise screening for prenatal cytomegalovirus and BK virus infections in newborn and young infants. I. CMV infections]. PMID- 6252455 TI - [Results of precise screening for prenatal cytomegalovirus and BK virus infections in newborn and young infants. II. BK virus infections]. PMID- 6252456 TI - [Lethal cytomegalovirus infection following immunologic reconstitution with cultivated thymus tissue in a child with severe combined immunologic deficiency]. PMID- 6252457 TI - [Nesidioblastosis of the pancreas: clinical aspects, diagnosis and therapy]. PMID- 6252458 TI - [Familial nesidioblastosis]. PMID- 6252459 TI - Tibial nerve H-reflex and F-wave studies in patients with uremic neuropathy. AB - The nerve conduction velocity along the whole length (knee to the spinal cord) of the 1a sensory and motor fibers of the tibial nerve, innervating the gastrocnemius and soleus muscles, of 29 control subjects and 32 patients with chronic renal failure was estimated with recently introduced electrophysiologic F wave and H-reflex methods. In control subjects and in uremic patients, the proximal sensory (1a) nerve conduction veloctiy (SNCV) was faster than the proximal motor nerve conduction velocity (MNCV), a finding which is attributed to the larger diameter and therefore faster conduction properties of 1a fibers. In uremic patients, the proximal 1a SNCV and MNCV were significantly slowed in comparison with the values in control subjects, while the terminal M-response latency was not significantly prolonged. PMID- 6252460 TI - [Oral long-term treatment of onychomycoses with ketoconazole (author's transl)]. PMID- 6252461 TI - [Determination of ketoconazole in hair from orally treated rats and guinea pigs (author's transl)]. PMID- 6252462 TI - Reduced activity of the red-cell sodium-potassium pump in human obesity. AB - Looking for evidence of reduced energy use in the cells of obese persons, we measured the numbers of sodium-potassium-pump units in erythrocytes from a group of 21 obese human subjects and found them to be reduced by 22 per cent as compared with those of nonobese controls (P <0.001). The cation-transport activity of the pump, as measured by 86rubidium uptake by the cells, we also reduced in parallel with decrease in pump units. An increased concentration of sodium in the red cells of obese subjectes was also found (9.6 +/- 0.7 vs. 7.1 +/ 0.6 mmol per liter of cells; P<0.01). This finding demonstrates independently the physiologic importance of reduced numbers of sodium-pump units and reduced pump activity as measured by ouabain binding and rubidium transport, respectively. The magnitude of the reduction in the number of pump units was found to be negatively correlated with the percentage of ideal body weight (r = 0.56, P<0.001); this observation suggests a possible role of abnormalities of the sodium pump in the pathophysiology of obesity. PMID- 6252463 TI - Bone response to phosphate salts, ergocalciferol, and calcitriol in hypophosphatemic vitamin D-resistant rickets. AB - We treated 11 children with vitamin D-resistant rickets with a phosphate mixture either alone (1.2 to 3.6 g per day) or combined with ergocalciferol (vitamin D2, to 50 x 103 IU per day) or with calcitriol (1,25-dihydroxyvitamin D3, 0.25 to 1 microgram per day). Serum calcitriol concentrations were normal in all patients. Calcitriol therapy circulating levels of the hormone to values above normal and increased intestinal phosphate absorption. In some patients this regimen decreased the need for phosphate supplements. None of the treatment regimens corrected the renal phosphate leak. Radiologic studies and bone histomorphometric analyses showed that phosphate (alone or with ergocalciferol) induced the mineralization of the growth plate but not of the endosteal bone surface. Combined calcitriol and phosphate therapy for a total of 2850 patient-days greatly improved the mineralization of trabecular bone. Short-term episodes of hypercalcemia were easily controlled by changes in calcitriol dosage. The data indicate that the combined calcitriol and phosphate regimen is useful in the treatment of vitamin D-resistent rickets. PMID- 6252464 TI - Polyclonal B-cell lymphoma during infection with Epstein-Barr virus. PMID- 6252465 TI - Inherited abnormality of neutrophil adhesion. PMID- 6252466 TI - Streptozocin alone compared with streptozocin plus fluorouracil in the treatment of advanced islet-cell carcinoma. AB - To evaluate the treatment of advanced islet-cell carcinoma, we randomly assigned 84 patients to streptozocin alone or streptozocin plus fluorouracil. Each regimen was given in five-day courses. The most frequent toxic effects were nausea and vomiting, mild and reversible renal toxicity, and bone-marrow depression with the combination regimen. The combination had advantages over streptozocin alone in overall rate of response (63 vs. 36 per cent) and in rates of complete response (33 vs. 12 per cent). There was no evidence of a preferential response among types of functional tumors. Objective responses were generally of long duration (median, 17 months) and of substantive clinical benefit. Treatment with the combination also yielded a survival advantage over treatment with streptozocin alone (medians, 26 and 16 1/2 months), but this difference is not statistically significant. In spite of gastrointestinal side effects, streptozocin combined with fluorouracil appears to be a valuable treatment for advanced islet-cell carcinoma. PMID- 6252467 TI - The confirmation and maintenance of smallpox eradication. AB - In December 1979, an independent scientific commission certified global eradication of smallpox. This conclusion was accepted at the 33d World Health Assembly of the World Health Organization (WHO) in May 1980. After WHO's intensified eradication program began in 1967, special certification procedures were used in 35 countries where the disease had been endemic and in 44 others at special risk. Six laboratories are known to retain variola virus; efforts have been made to ensure strict containment of these strains. There is no evidence that smallpox will recur as an endemic disease. Nevertheless, WHO will promote surveillance of smallpox-like disease and selected laboratory research on certain orthopoxviruses. These efforts will maintain confidence that smallpox has been eradicated and confirm that there are no animal reservoirs of variola virus. A more complete understanding of the orthopoxviruses, including monkeypox virus, should also be obtained. PMID- 6252469 TI - The effect of marijuana on reproduction and development. PMID- 6252468 TI - Ketoconazole in paracoccidioidomycosis: efficacy of prolonged oral therapy. AB - Ketoconazole, a new oral imidazole derivative, was employed for the treatment of five patients with paracoccidioidomycosis. The response was excellent, with objective clinical improvement and healing of both mucocutaneous and pulmonary lesions. Mycological and serological tests, as well as delayed hypersensitivity, were assessed and found to correlate with clinical improvement. Therapy was conducted for 12 months with a dose of 200 mg day in 2 patients; in the remainder the dose was reduced (100 mg day) after the first 6 months and maintained as such for an equal period. No side-effects or toxicity were noted despite prolonged treatment. The advantages of the new therapeutic approach are discussed. PMID- 6252470 TI - Marijuana research findings: 1980. Therapeutic aspects. PMID- 6252471 TI - Resolution, reconstitution and kinetics of the primary action of a hormone receptor. AB - The beta-adrenergic receptor (R) and the GTP binding protein (G) with which the receptor interacts were obtained in separate soluble fractions. Their recombination produced a hormone responsive system. In the presence of hormone the encounter of R with G in the reconstituted membrane occurs much faster than the subsequent R-induced activation of G. PMID- 6252472 TI - Mitotic EBNA-positive lymphocytes in peripheral blood during infectious mononucleosis. AB - Infectious mononucleosis (IM) is usually a benign lymphoproliferative disease caused by Epstein-Barr virus (EBV). Although EBV induces a state of continuous proliferation in infected B lymphocytes in vitro, the most prominent lymphoproliferation during IM is of activated, or atypical, T lymphocytes presumably responding to the virus or virus-infected cells. However, EBV genome carrying cells are known to be circulating during IM, as cultured peripheral blood leukocytes from patients with the disease give rise to continuous lymphoblastoid cell lines, each cell of which contains the EBV genome and expresses the EBV determined nuclear antigen (EBNA). The proposal that EBV infected cells in IM blood are not endowed with enhanced growth potential but are merely latently infected is supported by demonstrations that cells infected in vivo enter a viral replicative cycle when placed in vitro and that most cell lines derived from cultured lymphocytes of IM patients are infected by virus released in vitro. However the cells could also be capable of proliferation in vivo, since virus production and transformation are not mutually exclusive properties of EBV-transformed cells. Recently, EBNA has been detected in a very small fraction of peripheral blood lymphocytes of IM patients after T cells were first removed and this has been interpreted to indicate that cell transformation occurs in vivo during IM. The isolation of colonies of EBNA-positive cells from IM blood leukocytes cultures in soft agar suggests that at least some infected cells are capable of direct outgrowth into transformed cells. We report here direct evidence that circulating EBV-infected cells exhibit increased growth properties during IM. PMID- 6252475 TI - In vitro suppression of UGA codons in a mitochondrial mRNA. AB - Although both prokaryotic and eukaryotic messenger RNAs can be easily translated in heterologous protein-synthesizing systems, attempts to achieve correct synthesis of mitochondrial proteins by translation of mitochondrial mRNAs in such systems have failed. In general, the products of synthesis are of low molecular weight and presumably represent fragments of mitochondrial proteins. These fragments display a strong tendency to aggregate. Explanations have included the use by mitochondria of codons requiring a specialized tRNA population and the fortuitous occurrence within genes of purine-rich sequences resembling bacterial ribosome binding sites. In addition, the long 5'-leader sequences present in many mitochondrial (mt) RNAs may also contribute to difficulties in mRNA recognition by heterologous ribosomes. Recent sequence analysis of human mtDNA suggests that the genetic code used by mammalian mitochondria deviates in a number of respects from the 'universal' code, the most striking of these being the use of the UGA termination codon to specify tryptophan. That this may also apply in yeast mitochondria has been shown by Fox and Macino et al., thus providing an obvious and easily testable explanation for the inability of heterologous systems to synthesize full-length mitochondrial proteins. We confirm this explanation and describe here the in vitro synthesis of a full-length subunit II of yeast cytochrome c oxidase in a wheat-germ extract supplemented with a partially purified mitochondrial mRNA for this protein and a UGA-suppressor tRNA from Schizosaccharomyces pombe. PMID- 6252474 TI - S-adenosylmethionine--a novel regulator of aspartate kinase. AB - Man derives 70% of his dietary requirements of protein directly from the grains of cereals and legumes. These sources are respectively deficient in lysine (and secondarily threonine) and methionine and much effort is being devoted to their improvement. All three amino acids are derived from aspartate via a common metabolic pathway (Fig. 1) in which the first reaction catalysed by aspartate kinase is a key regulatory step limiting their production. In microorganisms, regulation of aspartate kinase occurs by a variety of mechanisms, commonly involving feedback inhibition of one or more isoenzymes by Lys plus Thr, Lys alone or Thr alone. On the other hand, Met control of this step does not seem to conform to a general pattern. Met represses, but does not inhibit aspartate kinase II of Escherichia coli; in other species Met can enhance or modify the effects of Lys or Thr. Similarly, varied controls involving Lys and Thr have been reported for the enzymes from higher plants with only one report of an effect of Met. In contrast to these previous results, we suggest here that the methionine derivative (S)-S-adenosyl-L-methionine (AdoMet) is an important regulator of the Lys-sensitive aspartate kinase of higher plants, and that this regulatory mechanism is highly conserved. There is thus a major synergistic interaction of the two nutritionally deficient amino acids Lys and Met to inhibit their own syntheses at the primary regulatory step in the pathway. PMID- 6252473 TI - VIP occurs in intrathyroidal nerves and stimulates thyroid hormone secretion. AB - Vasoactive intestinal polypeptide (VIP) is known to have powerful effects on the secretion from several endocrine and exocrine glands, and occurs in nerves with a ubiquitous distribution in the body. This infers that neuronal VIP may be a regulator of such secretion, and there is evidence that it is involved in the regulation of exocrine pancreatic function. Previous studies have shown that adrenergic and cholinergic nerves participate in the regulation of thyroid hormone secretion. We describe here combined immunohistochemical and immunochemical studies which show that the thyroid of several species is supplied with VIP-containing nerve fibres that surround blood vessels and run between and along thyroid follicles and that in the mouse neuronal VIP participates in the regulation of thyroid hormone secretion through a mechanism that is mediated by cyclic AMP. PMID- 6252476 TI - Crystallizing membrane proteins. PMID- 6252477 TI - Transcription and RNA processing by the DNA tumour viruses. AB - Messenger RNA synthesis by the DNA tumour viruses proceeds by a complex but versatile series of transcription and RNA processing steps. The major mechanistic features of this pathway are probably very similar to those used by the animal cell host itself. The viruses have, however, evolved intricate arrangements of protein coding sequences and sites for RNA initiation, polyadenylation and splicing which allow them to use their genetic information to maximum advantage. PMID- 6252478 TI - An examination of factors influencing adrenergic transmission in the pithed rat, with special reference to noradrenaline uptake mechanisms and post-junctional alpha-adrenoceptors. AB - Adrenergic mechanisms were analysed in the pithed rat to determine to what extent the actions of drugs observed in vitro are relevant in situ. The drugs examined were those which are known to block the neuronal or extraneuronal uptake of noradrenaline (cocaine, desipramine and corticosterone) or to be antagonists at post and/or pre-junctional alpha-adrenoceptors (prazosin and yohimbine) together with the antidepressant, mianserin, which has been implicated in several of these actions. These drugs were tested against the arterial diastolic pressor, cardiac chronotropic and vas deferens responses to sympathetic nerve stimulation, to indirect sympathomimetics or to direct sympathomimetics, which were chosen according to whether they were substrates for noradrenaline uptake processes or selective between adrenoceptors. Pressor and cardiac responses to sympathetic nerve stimulation or to intravenous noradrenaline were potentiated by blockade of neuronal uptake but only the pressor effect of noradrenaline was potentiated by blockade of extraneuronal uptake. The effects of the antagonists suggested that the pressor effects of noradrenaline and of sympathetic nerve stimulation result from a combination of activation of alpha 1- and alpha 2-adrenoceptors, but that the effect of noradrenaline had a relatively greater contribution from the alpha 2-adrenoceptors. Mianserin was found to potentiate adrenergic responses at low doses, to produce limited antagonism at post-junctional alpha 1-adrenoceptors in high doses but to have no detectable effect at post-junctional alpha 2 adrenoceptors. PMID- 6252479 TI - Development of and recovery from subsensitivity of the noradrenergic cyclic AMP generating system in brain. Effect of amphetamine following inhibition of its aromatic hydroxylation by iprindole. AB - Amphetamine given intraperitoneally (10 mg/kg b.i.d.) for 2 days did not alter either the basal level of cyclic AMP or the neurohormonal response of the cylcic AMP generating system to noradrenaline (NA). The same doses of amphetamine caused a significant reduction in the responsiveness to NA and the beta-adrenergic agonist isoprenaline following the inhibition of the aromatic hydroxylation by iprindole. The EC50 values (concentration of NA which causes half maximal cyclic AMP stimulation) were not significantly changed: 9.5 micro M (controls) and 11 micro M (iprindole + amphetamine). Following discontinuation of the drugs, the recovery from adrenergic subsensitivity to NA was complete within 1 week in the limbic forebrain while the adrenergic responsiveness in the cortex was still only 65% of its control value 3 weeks following discontinuation of the drugs. The subsensitivity in both limbic forebrain and cortex was linked to a decreased Bmax value of specific 3H-dihydroalprenolol binding without changes in the Kd values. The different rates of recovery from noradrenergic subsensitivity in limbic forebrain and cortex following withdrawal of the drugs were reflected in the density of beta-adrenergic receptors in the two brain regions. Since inhibition of the aromatic hydroxylation of amphetamine markedly prolongs the half life of the drug and prevents the accumulation of p-hydroxynorephedrine (a potential NA antagonist), the results support the view that homospecific down-regulation of the NA receptor coupled adenylate cyclase system in brain depends on a sustained and unhindered NA receptor interaction. PMID- 6252480 TI - Opioid receptors in the caudate nucleus can mediate EMG-recorded rigidity in rats. AB - Systemic administrations of opioids are known to induce "catatonia" or "lead pipe rigidity" in rats. The relevance of the caudate nucleus in inducing rigidity was tested. For this purpose, several opioids (or saline) were injected into the head of the caudate nucleus ("intrastriatal" injection) through an implanted cannula, and the electromyographical activity (EMG) was recorded in the gastrocnemius soleus muscle (GS). Morphine (7.5-3.0 microgram), injected unilaterally, induced a continuous EMG activity in the ipsilateral GS muscle. This effect could be antagonized by systemic administration of naloxone (1 or 2 mg/kg i.p.). D-ala2 met5-enkephalinamide (3 microgram) and levorphanol (22.5 microgram) induced an EMG activity, too, whereas an equimolar dose of dextrorphan was ineffective, indicating that this effect was stereospecific and mediated via opioid receptors in the caudate nucleus. The EMG activity observed after systemic morphine administration (15 mg/kg i.p.) was antagonized by intrastriatal injection of naloxone (5 microgram). From our results, it can be concluded that the striatum- at least the head of the caudate nucleus--plays an important role in mediating the rigidity observed after systemic administration of morphine and other opioids. PMID- 6252482 TI - [Electrical activity and Na, K-ATPase levels in an epileptic focus caused by application of penicillin to rat cerebral cortex and the effect of diazepam on them]. AB - Penicillin application to the rat brain motor cortex resulted in appearance of interictal discharges and seizures. After diazepam injection (2 mg/kg) a 100% increase in Na, K-ATPase activity of neuronal membranes in the epileptogenic focus was shown as compared to enzyme activity before diazepam injection. Interictal discharges and seizures changed in different ways after intramuscular injection of diazepam. The frequency and amplitude variation of interictal discharges increased but the seizures were suppressed. These effects increased with the dose of diazepam. It is suggested that the different influence of diazepam upon seizures and interictal discharges may reflect different mechanisms of these phenomena. PMID- 6252481 TI - Alpha 2-adrenoceptors modulating insulin release from isolated pancreatic islets. AB - Using rat isolated pancreatic islets, we investigated the effects of various alpha-adrenoceptor blocking agents on adrenaline-induced inhibition of glucose stimulated insulin release. Yohimbine was about 100 times more potent than prazosin in antagonizing the inhibitory effect of adrenaline. At concentrations of 10 micro M, phentolamine was about as effective as an antagonist as yohimbine, whereas dihydroergotamine, WB-4101 and phenoxybenzamine were less effective and prazosin produced very little antagonism. These results strongly suggest that post-synaptic alpha 2-adrenoceptors modulate insulin release from pancreatic islets. PMID- 6252483 TI - [Study of monosynaptic excitatory connections using a biomathematical model of neuronal interaction]. PMID- 6252484 TI - [Study of postinhibitory "rebound" in individual motor units of human hand muscles]. AB - Analysis of poststimulus histograms and interspike intervals of firing motor units showed that the burst following the silent period under evoked muscle contraction is the result of synchronous motoneuron escape from inhibition. Under strong evoked isotonic muscle contraction a true facilitation was revealed. The latency of this facilitation was too long for spinal monosynaptic reflex related to spindles elongation at the muscle relaxation stage. PMID- 6252485 TI - [Reactions of cat caudate nucleus neurons to cortical stimulation before and after destruction of nonspecific thalamic nuclei]. AB - In experiments on immobilized cats extracellular responses of caudate nucleus neurons were recorded during electrical stimulation of anterior sigmoideus and suprasylvius gyri. In the first set of experiments performed on cats with an intact thalamus the responses to stimulation of both cortical areas represented initial excitation (sometimes absent) followed by inhibition and late activation. Some qualitative and quantitative differences in the neuronal responses to stimulation of these cortical areas were found. The second set of experiments was performed on cats with preliminary destroyed unspecific thalamic nuclei. Changes were observed only in time course of late caudate neuronal responses. PMID- 6252486 TI - [Heterosynaptic facilitation in giant neurons of the cerebral ganglion of the horned Planorbis]. AB - Heterosynaptic facilitation evoked in the giant neuron of the Planorbis corneus cerebral ganglion by stimulation of the remote visceral nerve was more effective than facilitation achieved by paired stimulation of cerebral nerves. Its effectiveness depended not on the efficacy of the heterosynaptic input to the giant neuron, but on the strength of the connections between the chosen heterosynaptic input with neurons surrounding the giant cell. This finding as well as prolonged latency and slow rise-time of facilitation may indicate that the latter is of neurosecreory origin. The existence of a mechanism of drastic increase in the efficacy of synaptic connections may play an important role in animal habituation and during conditioning in particular, though such plasticsynaptic changes do not reflect the specificity of the conditioned reflex. PMID- 6252487 TI - [Effect of intracellular injections of cyclic adenosine monophosphate on the electrical characteristics of identified edible snail neurons]. AB - Electrical activity of silent RPa3, LPa2, LPa3, LPa8, LP11 neurons and spontaneously active RPa1 neuron was investigated as affected by iontophoretic intracellular cAMP injection. It is shown that in all cases the cAMP injection caused depolarization of the membrane; cAMP injection into the neuron when its membrane potential is clamped at the resting potential level evoked the appearance of transmembrane current (cAMP-current). External theophylline (1 mM/1) increased the amplitude and duration of vAMP-current approximately by 50%. It is concluded that variation in the cAMP concentration inside the neuron may alter the ionic permeability of its membrane, thus changing its electrical activity. PMID- 6252488 TI - [Ionic mechanisms of the transmembrane current induced by injection of cyclic adenosine monophosphate into identified edible snail neurons]. AB - The ionic mechanisms of transmembrane current evoked by cAMP injection (cAMP current) into identified neurons of the snail were studied using the voltage clamp. cAMP-current was shown to consist of two components. The early component has a reversal potential in the region of -5 divided by +20 mV and the late one in the region of -55 divided by -60 mV. It is suggested that the early component of cAMP-current is associated with an increase in the neuron membrane permeability mainly for sodium ions and the late one for potassium ions, respectively. In LPa8 neuron AMP injection also evoked the transmembrane inward current which was independent of the holding potential and was not accompanied by changes in the membrane conductance. PMID- 6252489 TI - [Kinetics of sodium current decay during normal axon membrane repolarization and in the presence of scorpion toxin]. AB - Decay of sodium currents in repolarization ("tail current") was studied in from axonal membrane. The decay in the membrane repolarization to -40 divided by -60 mV has two exponential components: fast and slow. The fraction of the slow component in the total "tail current" (theta M) decreases as the repolarization potential (Vp) becomes more negative; at Vp more negative than -80 mV "tail" follows practically one-exponential time course. When lengthening the test pulse (at the given Vp) the fraction of the fast component in the "tail" decreases quicker than that of the slow component, following approximately the kinetics of inactivation during the tests pulse. Scorpion toxin treatment results in slowing down "tail" kinetics mainly at the expense of increasing the fraction of the slow component. A kinetic diagram assuming two open state for the channel is suggested. A hypothesis is advanced that scorpion toxin, DDT and trinitrophenol have a common "site" to interact with the gating mechanism of the sodium channel. PMID- 6252490 TI - [Neurological disorders in hyper- and hypovitaminosis]. PMID- 6252491 TI - Silicon nephropathy: a possible occupational hazard. AB - A 37-year-old white male, working in a tile factory, presented proteinuria with no obvious tubular dysfunctional. Renal biopsy disclosed a mild focal segmental proliferative glomerulonephritis. Distinct alterations were found by electron microscopy, especially in the proximal tubular cells. Because of a history of heavy dust exposure the silicon content was determined in the kidney biopsy tissue. The finding of 150 mg/kg silicon on tissue dry weight supports the diagnosis of silicon nephropathy. PMID- 6252492 TI - [Growth hormone: with special reference to neurological surgery (author's transl]. PMID- 6252493 TI - Effect of electrical stimulation of the neurohypophysis on ACTH release in rats with hypothalamic lesions. AB - Electrical stimulation of the neural lobe (NL) of the pituitary induces a rise in plasma corticosterone indicating the release of adrenocorticotropin (ACTH) in rats pretreated with dexamethasone, morphine and pentobarbitone. 7-8 days after placing an anterolateral cut around the medial basal hypothalamus (MBH), the rats failed to respond with ACTH release to electrical stimulation of the NL; the number of nerve fibers and terminals in the NL decreased to less than 5% of the normal; and ACTH releasing activity of acid extracts of the NL was undetectable using both in vivo and in vitro tests, which are insensitive to vasopressin. After lesions of the paraventricular nuclei the stimulation of the NL elecited a rise of plasma corticosterone that was significantly less than that in the controls. These results suggest that the NL of the pituitary contains electrically excitable fibers capable of releasing corticotropin-releasing factor (CRF; distinct from vasopressin) and that these fibers probably originate from outside the MBH, with a portion of them coming from or through the paraventricular nuclei or their immediate vincinity. PMID- 6252494 TI - The kinetics of norepinephrine-induced stimulation of serotonin N acetyltransferase in bovine pineal gland. AB - Fresh pineal explants were cultured in medium 199 containing 0.1 mg/ml of ascorbic acid, 2 mM glutamine, and 0.1% BSA in 95% O2 and 5% CO2 from 1 to 10 h. Norepinephrine (10 micrometers) increased serotonin N-acetyltransferase (NAT) activity from 2.36+ / -0.23 to 6.98+ / -0.46 pmol product produced/mg protein/min (unit), without influencing tryptophan hydroxylase, 5-hydroxytryptophan decarboxylase, monoamine oxidase, or hydroxyindole-O-methyltransferase. Dibutyryl cyclic AMP (1 mM) also stimulated NAT from 1.39+ / -0.12 to 4.33+ / -0.65 U. The norepinephrine-induced stimulation of NAT was blocked by GABA (10 micrometers), by dl-propranolol (20 micrometers), by cycloheximide (30 micrometers), by puromycin (20 micrometers), but not by actinomycin D (10 micrometers). Comparing the kinetics of native and stimulated NAT, the occurred changes in Vmax with regard to both substrates - tryptamine (from 0.885 to 3.44 U) and acetyl CoA (from 3.45 to 9.10 U) - without changes in Km with respect to both tryptamine (Km = 5 micrometers) and acetyl CoA (Km = 50 micrometers). The results of this investigation are interpreted to indicate that the norepinephrine-induced stimulation of NAT may be due to enhanced protein synthesis involving translational or post-translational events. Furthermore, the enhanced protein synthesis is coupled through activation of beta-receptor and cyclic AMP mediated actions in pineal gland. The precise interrelationship between GABA and norepinephrine in mediating and perhaps in controlling the biological events in the bovine pineal gland still awaits clarificaton. PMID- 6252495 TI - Age-related changes in central nervous system beta-endorphin and ACTH. AB - Aging is associated with alterations in mood, thermoregulation, pain threshold, and stress response. Because these functions may be modulated by endogenous opiates, we measured immunoreactive ACTH with beta-endorphin in discrete brain areas and pituitary glands from rats aged 6 weeks (young), 6 months (mature), and 20-24 months (senscent). Beta-Endorphin and ACTH declined significantly with aging in the hypothalamus and corpus striatum. Beta-Endorphin and ACTH increased in the frontal lobe during early life; however, no change was noted after maturity. A discordant response with age was noted in the pituitary in that (ACTH did not change, while beta-endorphin increased early in life without change after maturity. Cerebellar tissue exhibited no immunoreactive ACTH or beta-endorphin. Age-related changes in brain and pituitary beta-endorphin and ACTH must be considered in the evaluation of the physiological aging process and when comparing studies of these neuropeptides. PMID- 6252496 TI - Oxytocin: major corticotropin-releasing factor secreted from diabetes insipidus rat posterior pituitary in vitro. AB - In diabetes insipidus (DI) rats, electrical stimulation of the posterior pituitary lobes in vitro promotes the release of corticotropin-releasing factor (CRF). The CRF activity is abolished by preincubation of the posterior lobe media with thioglycolate. Oxytocin, which is released concomitantly into the medium (3.2 mIU/lobe/20 min), accounts for the complete CRF effect. Neural lobe extracts from DI and normal rats contain 40-70% more CRF activity than can be explained by their content in vasopressin and/or oxytocin. The discrepancy between released and extracted CRFs suggests that hypothetical CRFs or potentiating factors are not released from nerve endings or have to be present in high concentrations to manifest their effect. PMID- 6252498 TI - GABA and benzodiazepine receptors in the offspring of dams receiving diazepam: ontogenetic studies. PMID- 6252497 TI - Dopaminergic mediation of beta-endorphin-induced prolactin secretion. AB - Intracisternal administration of synthetic human beta-endorphin increases plasma praolactin concentration, and this effect is blocked by naloxone. Drugs which stimulate dopamine receptors (apomorphine or bromocriptine) or increase availability of dopamine (pargyline) inhibited the effect of beta-endorphin on plasma prolactin. Drugs which antagonize dopamine receptors (haloperidol) or decrease availability of dopamine (alpha-methyltyrosine) potentiated the effect of beta-endorphin on plasma prolactin. Some of these drugs act only in neurons and not in anterior pituitary, supporting a brain site of action for these drug interactions with beta-endorphin which altered prolactin secretion. These pharmacological studies provide support for a concept of dopaminergic mediation of beta-endorphin-induced prolactin secretion. PMID- 6252499 TI - ACTH potentiates morphine-induced conditioned taste aversion. PMID- 6252500 TI - Action of mianserin and zimelidine on the norepinephrine receptor coupled adenylate cyclase system in brain: subsensitivity without reduction in beta adrenergic receptor binding. PMID- 6252501 TI - The effects of iron deficiency on brain biogenic monoamine biochemistry and function in rats. PMID- 6252502 TI - Portentiation of the analgesia induced in rats by morphine or [D-Ala2]-met enkephalinamide after inhibition of brain type B monoamine oxidase: the role of phenylethylamine. PMID- 6252503 TI - Opiate receptors in highly purified neuronal cell populations isolated in bulk from embryonic chick brain. PMID- 6252504 TI - Neurophysiological and behavioral maturation of cerebellar function studied with tremorogenic drugs. PMID- 6252505 TI - Functional antagonism by calcium of an intrinsic opioid mechanism in the guinea pig isolated ileum. PMID- 6252507 TI - Reversible osmotic blood-brain barrier disruption in humans: implications for the chemotherapy of malignant brain tumors. PMID- 6252506 TI - Recurrent Cushing's disease: successful treatment by pituitary irradiation or trans-sphenoidal hypophysectomy in two cases. AB - Two patients developed recurrent Cushing's disease 3 and 7 years after total bilateral adrenalectomy. In the first patient, a 65-year-old man, the adrenal tissue was not localized by radioactive cholesterol scintigraphy. Plain x-ray films of the skull revealed a normal sella turcica. Although clinical improvement resulted from the discontinuation of cortisone replacement therapy, urinary free cortisol levels remained elevated and the patient was treated with pituitary irradiation. Serum and urine cortisol levels gradually returned to normal. Four years after irradiation, the plasma adrenocorticotropic hormone (ACTH) concentration was elevated, but tomography of the sella turcica and urinary cortisol excretion remained normal. The second patient, a 41-year-old man, displayed elevated ACTH levels and x-ray evidence of a pituitary tumor at the time of recurrent Cushing's disease. After trans-sphenoidal hypophysectomy, the hypercortisolism abated and the ACTH concentration returned to normal. Adrenal scintigraphy frequently locates cortisol-secreting tissue in patients with recurrent Cushing's disease, and some investigators suggest treatment by the surgical removal of the adrenal remnant. Although the etiology of Cushing's disease is controversial, current evidence suggests that most cases result from ACTH-producing pituitary tumors. We suggest, therefore, that the anterior pituitary gland may be a more suitable target than the adrenal remnant for the treatment of recurrent Cushing's disease. PMID- 6252508 TI - The effects of dibutyryl cyclic adenosine monophosphate on the degeneration and regeneration of crush-lesioned rat sciatic nerves. PMID- 6252509 TI - Sensory nerve stimulation and evoked cerebral potentials. AB - Cerebral potentials were evoked by stimulating sensory fibers of the median, ulnar, radial, musculocutaneous, sural, superficial peroneal, and saphenous nerves. The sensory nerve action potential was simultaneously recorded from these nerves, allowing comparison of peripheral and central sensory conduction times. Somatosensory potentials (SEPs) elicited by sensory nerve stimulation are of particular value in evaluating proximal segments of peripheral as well as central somatosensory pathways. PMID- 6252510 TI - Continuous cataplexy in a patient with a midbrain tumor: the limp man syndrome. AB - A patient with glioblastoma of the rostral brainstem and hypothalamus exhibited bilateral internuclear ophthalmoplegia and vertical nystagmus; he suffered episodes of cataplexy, narcolepsy, and sleep paralysis. A peculiar fluctuation of posture and tone ("limp man syndrome") proved to be a manifestation of continuous cataplexy, as documented by H-reflex recordings. This is the first report of a remarkable movement disorder caused by continuous, fluctuating, partial cataplexy, and is the second report of an association between cataplexy and a tumor of the rostral brainstem. PMID- 6252511 TI - Multiple sclerosis de novo CNS IgG synthesis: effect of ACTH and corticosteroids. AB - ACTH gel and corticosteroids were given to 28 clinically definite multiple sclerosis (MS) patients to determine whether de novo central nervous system (CNS) IgG synthesis (rate and cerebrospinal fluid [CSF] IgG oligoclonal bands) could be eradicated. The most effective treatments were ACTH gel and ACTH gel followed by prednisone, all 11 patients had a significant reduction in rate (p < 0.05), which became normal in eight patients (< 3.3 mg per day). In order of effectiveness, the other drugs used were: dexamethasone or prednisone given orally, and hydrocortisone administered intrathecally. For most treatments, reduction of the rate of CNS IgG synthesis occurred within days and persisted for months after cessation of treatment. The MS CNS immune reaction was not eradicated when IgG synthesis rate became normal, because CSF IgG oligoclonal bands persisted. None of the chronic progressive, severely disabled patients demonstrated significant change in neurologic function or persistent adverse effects. PMID- 6252512 TI - Penicillamine-associated myasthenia gravis. AB - Electroneuromyographic studies have been reported as abnormal in only 9 of 23 cases of penicillamine-associated myasthenia gravis (MG). We report a patient with rheumatoid arthritis who developed clinical and electrodiagnostic evidence of myasthenia 7 months after beginning penicillamine therapy. Six months after discontinuing penicillamine, it was possible to discontinue anticholinesterase medications. With clinical improvement, electrodiagnostic studies (including single-fiber electrmyography) improved, serum antibody titers to human muscle acetylcholine receptor fell, and lymphocytes became more responsive to the nonspecific mitogen phytohemagglutinin. Evidence suggests that penicillamine associated myasthenia is a distinct syndrome rather than the chance occurrence of two diseases. This syndrome is clinically and electrophysiologically distinguishable from idiopathic myasthenia only by the high remission rate after penicillamine is discontinued. PMID- 6252514 TI - Assumptions in the radiotherapy of glioblastoma. AB - In the light of advances in computerized tomography (CT), we have retrospectively evaluated the assumptions that underlie the radiation therapy of glioblastoma: (1) No neuroradiologic technique provides an accurate delineation of tumor bulk and location, (2) glioblastoma is commonly multicentric, and (3) a major source of therapeutic failure is recurrence beyond radiotherapy fields. 1. CT scans, performed on glioblastoma patients within 2 months of postmortem examination, defined both gross and microscopic tumor extent (within a 2-cm margin) in all but 6 of 35 patients evaluated. The major source of error was subependymal spread (four patients). 2. Multicentricity occurred in only 4% of untreated and 6% of treated (radiotherapy with or without chemotherapy) patients. All multicentric lesions were identified on CT scans. 3. Serial CT scans on 42 patients revealed that glioblastoma recurred within a 2-cm margin of the primary site in 90%. Occurrences outside this margin were accurately delineated by CT in all instances. Because most patients show recurrence within or in close proximity to the original site, current radiation doses would appear to be inadequate for therapy of the primary tumor. CT scan accuracy may permit smaller-field and higher-dose irradiation therapy for glioblastoma. PMID- 6252513 TI - Neuroelectric blocking activity and plasmapheresis in amyotrophic lateral sclerosis. AB - Neuroelectric blocking activity, similar in nature to that previously observed in sera from patients with multiple sclerosis, has been observed in sera from 18 patients with amyotrophic lateral sclerosis. Results concerning the application of plasma exchange to this patient population are also described. PMID- 6252515 TI - Fatal Guillain-Barre syndrome after the national influenza immunization program. AB - Fifty-eight fatal cases of Guillain-Barre syndrome (GBS) were reported during the 1976 to 1977 National Influenza Program: Thirty-two (58%) of these patients had received the A/New Jersey influenza vaccine. The mean interval from vaccination to onset was 3.9 weeks, and the incidence of preceding illness in vaccinated or unvaccinated patients was similar. Fifty-eight percent had at least one chronic disease before onset. The clinical features were similar in vaccinated and unvaccinated patients. Most deaths followed medical complications of respiratory paralysis: Fifteen had pneumonia, 29 (83%) died suddenly, 15 had sudden arrhythmias or hypotension, and 7 had myocardial infarction or pulmonary embolus. PMID- 6252516 TI - Herpetic brainstem encephalitis. AB - A fatal case of brainstem encephalitis presented as an acute lateral medullary syndrome. Pathologic examination showed a focal encephalitis along the roots and the intramedullary portion of the right vagus and glossopharyngeal nerves. Herpesvirus particles were demonstrated by electronmicroscopy of formol-fixed material. This is the second known case of herpetic brainstem encephalitis confirmed by postmortem examination and the only one in which the infection was limited to the brainstem. This case and a review of previously reported cases suggest that the viral infection could proceed to the brainstem through the vagus and glossopharyngeal nerves, probably from a source of latent herpetic infection in the respective ganglia. PMID- 6252517 TI - Evaluation of diagnosis and non-surgical therapy in 24 children with a pontine tumour. AB - In a retrospective study of 24 pontine tumours in children, the problem of diagnosis is reviewed. Diagnosis is primarily on clinical signs and symptoms. In accordance to the literature, intracranial hypertension is exceptional. Bladder retention, seldom mentioned in the literature, seems an important sign of an intramedullary process. In 17 cases arteriography was positive; in 7 cases a combinatin with ventriculography was necessary to confirm the diagnosis. The principal aim of the study was to evaluate the effect of the non-surgical therapy. Without any therapy survival after diagnosis is about 2 months; with radiotherapy (3.250 a 6.650 R) prognosis reaches 9 months; irradiation with chemotherapy (cyclofosfamide, amethopterine, 6-mercaptopurine, vincristine, CCNU) gives no significant better results. Children, who respond positively after 2 or 3 weeks of therapy, have a better prognosis than those who do not. There are two exceptions with long survival (7 and 9 years). The influence of the combined therapy on personality and cognitive functions is discussed in these two cases. PMID- 6252518 TI - [Prostaglandins and peptic ulcer disease]. AB - The action of prostaglandins with regard to ulcers is made clear by their inhibition of gastric secretion, on the one hand, and their so-called cytoprotective effect, on the other. Experimental data are used in a summary of the explanations offered of the mechanisms underlying these two effects. In addition, attentions is directed to the possible role of the prostaglandins in gastric physiology, and hence in the physiopathology of ulcers. The therapeutic results obtained with prostaglandins in the management of gastroduodenal ulcer offer firm grounds for supposing that further developments will take place in the clinical field. PMID- 6252519 TI - [Metabolic changes induced with salmon calcitonin in post-menopausal osteoporosis]. AB - 10 patients suffering from post-menopausal osteoporosis were subjected to venous infusion of salmon calcitonine at a dose of 100 U.M.R.C. Essential inital biochemical data were hypocalcaemia associated with plasma increase in AMPc and, in the late phase, an increase in urinary excretion of phosphate and AMPc. In addition to conserving its physiological properties in osteoporotic disease also, the hormone is thus able to provoke a secondary secretion of parathormone. The use of CT in the treatment of post-menopausal osteoporosis is therefore recommended not only because of its evident action on bone reabsorption processes, which usually predominate in this dysmetabolic disease of the skeleton, but also in the indirect secretion of parathyroid hormone which is capable of positively affecting synthesis of 1-25 (OH)2 D3 and intestinal calcic absorption. PMID- 6252520 TI - Catecholamines and aversive learning: a review. AB - Experimental evidence is reviewed for the implication in aversive learning of the catecholamines, in particular noradrenaline and dopamine and the pituitary adrenocortical system, in particular adrenocorticotrophic hormone and corticosterone. Depending on task difficulty peripheral neural noradrenaline may be an important factor in aversive learning whereas brain catecholamines are important regardless of task difficulty. The adrenocortical system, as indexed by plasma levels of corticosterone, is also implicated in complex aversive tasks. To date, no convincing empirical evidence exists for a link mechanism between the brain catecholamine system and the adrenocortical system following aversive learning. Earlier behavior theories of aversive learning are reformulated in the light of more recent findings on neuroregulation. PMID- 6252521 TI - Glomus bodies and tumors. PMID- 6252522 TI - A cluster of septic complications associated with illegal induced abortions. AB - Between August 7 and October 14, 1977, Clostridium perfringens organisms were isolated from endometrial and/or blood specimens from 3 women who had been hospitalized in McAllen, Texas, after having had illegal induced abortions. One of the women died of clostridial septicemia. A single abortionist was suspected in these 3 cases. The authors investigated the illnesses of these 3 women and those of 6 other women who were hospitalized at some time from January through October 1977 after having had illegal abortions but did not identify a common abortionist. The patient who died was a Medicaid-eligible woman who had had an abortion performed by a nonphysician after public funding of abortion was restricted in Texas as of August 5, 1977. The authors examined the medical records of all 230 women hospitalized in McAllen General Hospital with abortion complications from 1977 through January 1978. The local effect of restriction of public funds for abortion was to be studied. The incidence of women admitted to the hospital with febrile abortion complications after August 5, 1977, did not differ from that of women admitted from January 1 through August 4, 1977. However, the incidence of hospitalization of Medicaid-eligible women with abortion-related complications was greater after August 5 than it was in the earlier period. PMID- 6252523 TI - Specific binding of human chorionic gonadotropin to human corpora lutea in the menstrual cycle. AB - Luteal tissue from 26 premenopausal women undergoing surgery for nonendocrine disease was examined for specific binding to human chorionic gonadotropin. Results showed a nadir in the percentage of binding on day 10, with a gradual increase until maximal binding was obtained on days 22 through 26. Binding then markedly declined to that seen on day 1 of the menses and decreased gradually to its lowest level on day 10. PMID- 6252524 TI - Anovulation with estrogen production: receptor disorders? AB - Receptor antibodies have been implicated in the pathogenesis of several autoimmune disorders such as Graves disease. The authors hypothesized that serum antibodies against the luteinizing hormone (LH) receptor existed in women with chronic anovulation syndrome and continuously stimulated the ovaries. Twenty patients with the clinical diagnosis of anovulation with estrogen production were studied. The effects of serum globulins on the binding of 125I-labeled human chorionic gonadotropin (hCG) to ovarian receptors in the patients were compared with the effects in age-matched controls. These studies did not demonstrate significant inhibition of 125I-hCG binding to ovarian receptors by immunoglobulins of patients with anovulation and estrogen production in comparison with those of control subjects. This finding suggests that the cause of anovulation with estrogen production is not an autoimmune phenomenon involving the LH receptor of the human ovary. PMID- 6252525 TI - [On the chemotherapy of lung cancer (author's transl)]. PMID- 6252526 TI - [Lung cancer - a retrospective survey comments on radiotherapy of lung cancer (author's transl)]. PMID- 6252527 TI - Ultrastructural localization of phosphatases and cytochrome oxidase in the dog parathyroid gland. PMID- 6252528 TI - Limited gallium scans and angiotensin converting enzyme in granulomatous uveitis. AB - The use of serum angiotensin converting enzyme (ACE) and limited gallium scans of the head, neck, and chest for patients with granulomatous uveitis is described. Mean serum ACE activity was elevated in patients with granulomatous uveitis regardless of the presence of systemic sarcoidosis. Furthermore, pathologic gallium uptake was noted in lacrimal glands, parotid glands, and lungs in some cases. These results indicate that sarcoidosis may be more common than previously believed in these patients. PMID- 6252529 TI - Floating test (Rossipal) for screening patients with fat malabsorption. PMID- 6252530 TI - Activity of quinfamide against natural infections of Entamoeba criceti in hamsters: a new potent agent for intestinal amoebiasis. AB - A novel tetrahydroquinolinyl ester, quinfamide, administered orally in multiple doses for 3 days had an ED50 of 0.25 mg/kg/day (total dose 0.75 mg/kg) for eradicating Entamoeba criceti in hamsters in several tests. It was significantly more active by direct comparison than 3 commercially available amoebicides and at least as active as 2 other esters of the parent compound, 1-(dichloroacety) 1,2,3,4-tetrahydro-6-quinolinol. After administration of a single dose, ED50 calculations for quinfamide averaged 0.9 mg/kg. Quinfamide was considerably more active than the other tetrahydroquinolinols, diloxanide furoate and teclozan, and it was approximately 1.5 times more active than etofamide; a statistical significance between the latter 2 drugs could be demonstrated in one of 4 tests. Administered prophylactically, quinfamide was shown to protect hamsters from re infection with E. criceti. It also inhibited propagation of E. histolytica in vitro at a concentration of 20 microgram/ml. No adverse effects were noted in rodents after a single dose as high as 10 g/kg. Daily administration to monkeys of doses up to 500 mg/kg for as long as 37 days produced no pharmacological aberrations during or after medication; haematological studies and urine analyses were normal and no gross or microscopical tissue changes attributable to quinfamide were observed. No toxicity was revealed following acute (2 g/kg) and chronic (500 mg/kg/day x 31 days) administration of the drug to dogs and rats, respectively. PMID- 6252531 TI - [Adrenal glucocorticoid function in hypoxic hypoxia]. PMID- 6252532 TI - [Morphological diagnosis of carcinoid tumor]. PMID- 6252533 TI - Melanotic neuroectodermal tumor of infancy. PMID- 6252534 TI - [Studies on the formation of oncornavirus particles in cell culture]. PMID- 6252535 TI - Malignant facial tumors in children: radiologic evaluation. Stressing value of conventional and computerized tomography. AB - Twenty-five cases of malignant tumors of the face in children under 16 years of age were reviewed. In each case the presenting complaint was related to a mass of the face, without a known primary malignancy. Rhabdomyosarcoma was the most common malignancy, followed by equal numbers of histiocystic malignancies and malignant lymphomas. Chloroma and neuroblastoma were less common. Plain films were obtained on every patient and were always felt to be an appropriate part of the work-up. The plain films suggested or made the diagnosis of malignancy in 16 of the patients. The most helpful additional study was tomography. CT was the modality of choice for tumors originating in or extending into the orbit, and for intracranial extension. Xeroradiography best demonstrated a superficial soft tissue tumor. In evaluating facial malignancies, the number and sequence of examinations must be individualized according to the presentation. PMID- 6252536 TI - Chediak-Higashi syndrome: abnormal lysosomal enzyme levels in granulocytes of patients and family members. AB - Nine lysosomal enzyme activities were examined in granulocytes and lymphocytes from two unrelated patients with Chediak-Higashi syndrome (CHS) in "accelerated phase" and from their family members. In CHS granulocytes, there was a marked reduction of alpha-mannosidase (E.C. 3.2.1.24), alpha-galactosidase (E.C. 3.2.1.22), and alpha-fucosidase (E.C. 3.2.1.51) activities, which were below 21, 24, and 43% of mean control values, respectively. In CHS lymphocytes, beta glucuronidase (E.C. 3.2.1.31) and alpha-mannosidase activities were also decreased. In granulocytes of family members, the activities of acid phosphatase (E.C. 3.1.3.2), N-acetyl-beta-glucosaminidase (E.C. 3.2.1.30), aryl sulphatase (E.C. 3.1.6.1), and beta-glucuronidase were significantly higher than the control values (P < 0.001), which were 262, 218, 414, and 180% of mean control values. Neither the inhibitor in CHS granulocytes nor the activator in the heterozygous granulocytes to those enzymes could be found by mixing experiments with normal ones. PMID- 6252538 TI - [Radiation treatment of angiofibroma and hemangioma in the nasopharynx and nasal cavity (author's transl)]. PMID- 6252537 TI - ACh-evoked complex membrane potential changes in mouse submaxillary gland acini. A study employing channel blockers and atropine. AB - The responses in membrane potential and resistance of acinar cells to iontophoretically applied acetylcholine (ACh) were investigated using intracellular micro-electrode recording in superfused segments of mouse submaxillary gland. For measurements of membrane resistance and acetylcholine equilibrium potential (EACh), two micro-electrodes were inserted into neighbouring communicating cells. Current could be injected through one of the electrodes. The pattern of membrane potential change induced by ACh depended on the resting potential. Simple hyperpolarizations were induced at low resting potentials, while biphasic potential changes (depolarization followed by hyperpolarization) or simple depolarizations were observed at relatively high resting potentials. A similar dependence of the ACh induced potential change on the resting potential was obtained in experiments in which the resting membrane potential was set at different levels by injecting direct current and stimulating the same cell with equal doses of ACh. The ACh equilibrium potential ranged widely between -45 and -75 mV. Under special conditions the conversion in response to ACh from a hyperpolarization to depolarization could be obtained without change in resting potential. Small doses of ACh evoked simple depolarization, while medium doses induced biphasic responses and large doses of ACh caused hyperpolarization. The effect of a low concentration of atropine on the response was an initial block of hyperpolarization followed by a secondary block of depolarization. Intracellular injection of TEA ions converted the ACh induced potential response from hyperpolarization to depolarization. Both the depolarizing and hyperpolarizing ACh responses were accompanied by a marked reduction in membrane resistance. The depolarization was abolished by a severe reduction in external Na concentration, while the hyperpolarization was sensitive to alternations in external K concentration. These results indicate that some of the complex responses in submaxillary gland acinar cells to ACh may be explained by the interaction between two different kinds of potential change (Na dependent depolarization and K dependent hyperpolarization). PMID- 6252539 TI - [Outbreak of hand, foot and mouth disease in a day-nursery. A new clinical form? (author's transl)]. AB - Ten cases of vesicular eruption affecting primarily the hands (4/10) and feet (6/10) occurred in a day-nursery for infants. An enterovirus related to coxsackie A 16 virus was isolated from two vesicular fluids and nine stools. The fact that the outbreak took place in the winter, the rarity of pharyngeal lesions (2/10), the high incidence of foot lesions and the presence of listlessness as only associated symptom lead to a discussion of the relationship between this small epidemic and true hand, foot and mouth disease. PMID- 6252540 TI - [Physiology and pathology of bactericidal activity in human polymorphonuclear neutrophils (author's transl)]. AB - Blood polymorphonuclear neutrophils defend man against aggressions from pathogens. Under the combined influence of granulocytic and non-granulocytic factors, the defensive process develops by steps: the neutrophil moves towards the pathogenic organism which, one reached, is engulfed and killed. The killing systems of the cell are either oxygen-dependent or independent. the oxygen dependent system is triggered off by stimulation of the cell membrane and involves various reactions, including cyanide-resistant oxygen consumption, production of activated oxygen, oxygen peroxide and halogenisation of the pathogen membrane. Impairment of the killing activity requires quantitative assessment of its various components in the presence of autologous or control serum with the view of: determining the origin (granulocytic or non-granulocytic) of the impairment, and identifying the step in oxygen metabolism that is affected. In the vast majority of non-granulocytic insufficiencies the cause lies in defective opsonins. In granulocytic insufficiencies, global failure of the system indicates chromic granulomatous disease, a syndrome that is now being dismembered. Defective halogenisation should lead to testing for deficiency of myeloperoxidase or abnormal degranulation. The non oxygen-independent bactericidal system, although highly effective in vitro, appears to be less important in vivo than the oxygen-dependent system. Little is known of its pathology. PMID- 6252541 TI - Two genes for the major heat-shock protein of Drosophila melanogaster arranged as an inverted repeat. AB - The physical maps of three cloned D. melanogaster DNA fragments with genes for the 70,000 dalton heat-shock protein (hsp 70) are presented. Fragment 122 contains two genes in diverging orientation, forming an inverted repeat around a central spacer. The other two fragments, which are found as polymorphic variants in the fly population, have related structures; they differ by the deletion or the insertion of large DNA segments. The sequence homologies between 122 and a plasmid with two hsp 70 genes in tandem repetition was investigated by heteroduplex analysis. In addition to the basic gene units, the segments share other homologous sequence elements which are found in different combinations near the beginning of the genes. PMID- 6252542 TI - Isolation of DNA from agarose gels using DEAE-paper. Application to restriction site mapping of adenovirus type 16 DNA. AB - A new method for isolating DNA from agarose gels is described. The method involves the simultaneous transfer of all DNA-fragments from an agarose slab gel onto DEAE-cellulose paper and the elution of the individual fragments from the paper with 1 M NaCl. DNA isolated from agarose gels in this way is susceptible to cleavage with several restriction endonucleases, and can be labeled in vitro with E coli DNA-polymerase I, T4 DNA-polymerase and T4 polynucleotide kinase. We have used the method to construct restriction endonuclease maps of adenovirus type 16 DNA. PMID- 6252543 TI - Evidence for nonrandom alterations in a fraction of the highly repetitive DNA of a eukaryote. AB - Although the DNA of the red crab Geryon quinquedens has no patent satellites, a large fraction (approximately 40%) is highly repetitive. Treatment of total DNA by Hind III produces fragments comprising 5-6% of the genome. While the sizes of some of these fragments form an arithmetic series based on an 81 bp repeating unit, the amounts of the multimers differ significantly from distributions observed for multimeric series in the DNAs of other eukaryotes. In red crab DNA, the amounts of some of the multimers suggest that they may have undergone as much as four times the divergence as the others. Other data, however, are more compatible with the conclusion that there has been selective amplification of segments of highly repeated DNA which results in the enhanced amount of specific multimers. These results indicate the presence of a nonrandom process in the evolution of the highly repetitive DNA. Selective mutation alone seems insufficient to explain these results. PMID- 6252544 TI - Organization and expression of the mitochondrial genome of plants I. The genes for wheat mitochondrial ribosomal and transfer RNA: evidence for an unusual arrangement. AB - We show here that mitochondrial-specific ribosomal and transfer RNAs of wheat (Triticum vulgare Vill. [Triticum aestivum L.] var. Thatcher) are encoded by the mitochondrial DNA (mtDNA). Individual wheat mitochondrial rRNA species (26S, 18S, 5S) each hybridized with several mtDNA fragments in a particular restriction digest (Eco RI, Xho I, or Sal I). In each case, the DNA fragments to which 18S and 5S rRNAs hybridized were the same, but different from those to which 26S rRNA hybridized. From these results, we conclude that the structural genes for wheat mitochondrial 18S and 5S rRNAs are closely linked, but are physically distant from the genes for wheat mitochondrial 26S rRNA. This arrangement of rRNA genes is clearly different from that in prokaryotes and chloroplasts, where 23S, 16S and 5S rRNA genes are closely linked, even though wheat mitochondrial 18S rRNA has previously been shown to be prokaryotic in nature. The mixed population of wheat mitochondrial 4S RNAs (tRNAs) hybridized with many large restriction fragments, indicating that the tRNA genes are broadly distributed throughout the mitochondrial genome, with some apparent clustering in regions containing 18S and 5S rRNA genes. PMID- 6252545 TI - A method for detecting the coding DNA for a protein of known sequence in a collection of chimeric plasmids constructed with cDNAs. AB - A rapid screening method for recognising plasmids containing copies of cDNA corresponding to proteins of known amino acid sequences, is described. The method is based on the computer prediction of the possible restriction sites in the cloned DNAs. It was tested on a series of proteins with known coding DNA sequences and a series of plasmid cloned cDNAs made from pure chicken globin mRNA. PMID- 6252547 TI - Non-specific binding of restriction endonuclease EcoR1 to DNA. AB - Restriction endonuclease, EcoRl cleaves the DNA sequence (see formula in text) at the points indicated. Under certain conditions, EcoRl activity is observed when (see formula in text) is cut. Mg2+ is required for both activities. We find that in addition to binding to the above sites, EcoRl will also bind, although less strongly, to DNA containing neither site. Methyl acetimidate, which reacts specifically with lysine residues, inactivates the enzyme. This specific effect can be prevented by SV40 DNA and lambda DNA which contain EcoRl and EcoRl sites, by 0X174 DNA, which has only EcoRl sites and also by Polyd(AT) and polyd(GC) containing neither site. Protection occurs in the absence or presence of magnesium. The significance of this non-specific binding, both for the use and mechanism of EcoRl will be discussed. PMID- 6252546 TI - Evidence implying DNA polymerase beta function in excision repair. AB - Comparison was made of the ability of calf thymus DNA polymerases alpha and beta to replicate the following templates: native E. coli CR-34 DNA (T-DNA), calf thymus DNA activated by DNase I (act.DNA), BU-DNA (from E. coli CR-34 cells cultured on BUdR-containing medium) with damages resulting from incomplete excision repair, as well as thermally denatured act.DNA and BU-DNA (s.s.act.DNA and s.s.BU-DNA). 3H-TTP incorporation during extensive replication of act.DNA was similar for both enzymes, being, as expected, 40 times higher than for T-DNA. Likewise, the differences in the yield of the s.s.act.DNA or s.s.BU-DNA replication between both enzymes were negligible. In contrast, damaged native DNA was 6 - 30 times more extensively replicated by DNA polymerase beta than alpha. We propose that this is due to the greater ability of DNA polymerase beta compared with alpha to replicate single-stranded gaps, the presence of which is more likely in damaged BU-DNA than in T-DNA and act.DNA. PMID- 6252548 TI - [Cavernous neoplastic metastases to the lungs in children (author's transl)]. PMID- 6252549 TI - [Clinical evaluation of a derivative of 6-beta-amidino penicillanic acid (preparation HX) in urinary tract infections]. PMID- 6252550 TI - Managing the patient with peripheral neuropathy. AB - Peripheral neuropathy may be a minor, even unrecognized, clinical problem, or it may be severe and virtually disabling. As in any chronic disorder, the physician's role is to look for treatable disease and to teach patients about the symptoms and natural history of the dysfunction as well as methods for coping with it. The physician can help patients by explaining how to contend with a damaged peripheral nervous system on a daily basis, even if healing or significant organic relief cannot be achieved. PMID- 6252551 TI - Oat cell carcinoma mimicking leukemia. AB - A patient with oat cell carcinoma had circulating carcinoma cells, which initially suggested a diagnosis of acute leukemia. The correct diagnosis was made only by histopathologic examination of the bone marrow. A case of a similar bone marrow disorder, which developed after diagnosis of oat cell carcinoma, is also presented. PMID- 6252552 TI - Skin disorders of the vulva. PMID- 6252553 TI - Skin cancer. PMID- 6252555 TI - The non-impulsive stretch-receptor complex of the crab: a study of depolarization -release coupling at a tonic sensorimotor synapse. PMID- 6252554 TI - [Biospecific chromatography of proteases (review)]. PMID- 6252556 TI - Coxsackievirus B3-positive mononuclear leukocytes in peripheral blood of Swiss and athymic mice during infection. PMID- 6252557 TI - Central and hormonal regulation of renin release by baboon kidneys. PMID- 6252558 TI - Role of prostaglandins, beta-adrenoceptors, and the central nervous system in the control of renin release in conscious sodium-depleted rats. PMID- 6252560 TI - Copurification of beta-adrenergic catecholamine receptors and hormone-sensitive adenylate cyclase with uterine smooth muscle plasma membranes. PMID- 6252559 TI - Effects of methionine-enkephalin on intestinal circulation and oxygen consumption. PMID- 6252561 TI - Dissimilar effects of nicotinamide and inosine, putative endogenous ligands of the benzodiazepine receptors, on pentylenetetrazol seizures in four strains of mice. AB - In adult male albino BALB/c mice inosine (INS, 100 and 200 micrograms, intraventricularly) prolonged the latency of pentylenetetrazol (PTZ) seizures while nicotinamide (NAM) exerted an opposite effect. In adult male C57BL/6 mice INS decreased lethality after PTZ while NAM increased it. In adult male albino SHR (bred from Swiss) and in adult male CC57BR mice INS and NAM did not modify the effect of PTZ. Both INS and NAM administered ICB induced short-lasting locomotor excitement in albino SHR and BALB/c mice but not in C57BL/6 or CC57BR mice. Pretreatment with INS (300 mg/kg, IP) prolonged the latency of PTZ seizures only in SHR mice. Pretreatment with NAM was ineffective in all strains tested. Chronic treatment with NAM and INS (100 mg/kg, IP, daily for 5 days) in SHR mice did not modify the effect of PTZ. The data obtained emphasize the importance of the appropriate choice of mouse strain for studies on INS and NAM as puntative endogenous ligands of the BDZ receptor (BDZR). The opposite effects of INS and NAM raise doubts that these two substances could play the same or similar roles in the function of a type of BDZR which is related to the action of PTZ on the central nervous system. PMID- 6252562 TI - Effects of morphine, beta-endorphin and naloxone on catecholamine levels and sexual behavior in the male rat. AB - Intraperitoneal administration of the opiate antagonist naloxone hydrochloride (30 mg/kg) to sexually experienced male rats caused a significant reduction in mount and intromission latencies, number of mounts preceding ejaculation and ejaculation latencies. Intraperitoneal adminstration of naloxone (30 mg/kg) also stimulated persistant non-copulators to begin mating and to ejaculate within a twenty minute test period. Conversely, intraperitoneal administration of morphine sulphate (6 mg/kg) as well as intraventricular injection of the endogenous opiate beta-endorphin (6 micrograms) produced a complete loss of copulatory behavior in male rats. The deficit in sexual behavior induced by beta-endorphin was correlated with a significant increase in hypothalamic norepinephrine levels. It is suggested that the endogenous opiates may be involved in the mediation of sexual behavior via an interaction with central catecholaminergic systems. PMID- 6252563 TI - Oxidation and subsequent glucuronidation of 3,4-benzopyrene in everted intestinal sacs in control and 3-methylcholanthrene-pretreated rats. AB - The metabolism of 3,4-benzopyrene in the wall of isolated everted intestinal sacs was studied in control and 3-methylcholanthrene induced rats. The luminal (outer) side of the intestine was perfused with a 100-mumol/l concentration of 3,4 benzopyrene in Krebs-Ringer's bicarbonate buffer supplemented with 5% glucose and 2% albumin. A thin-layer chromatography assay method was used to analyze benzo(a)pyrene metabolites. After the pretreatment of rats with 3 methylcholanthrene, the amount of hydroxylated metabolites was about 1.5-fold and the amount of consequent glucuronides was about 3-fold in comparison with the controls. 3-Methylcholanthrene induction mainly increased the production of 3- and 9-hydroxybenzopyrene and dihydrodiols. The glucuronidation of 3- and 9 hydroxybenzopyrene was enhanced by 3-methylcholanthrene but the conjugation of dihydrodiols was nonresponsive to induction. Only small amounts of glucuronides were present in the inner (serosal) side of the intestinal sac. The data suggest different responses of various benzo(a)pyrene metabolites to induction in the intestinal mucosa. In addition to metabolic functions the intestinal mucosa may function as an excretory organ for polycyclic aromatic hydrocarbons entering the body. PMID- 6252564 TI - Influence of cannabinoids on somatic cells in vivo. AB - Chromosomal and nuclear aberrations in bone marrow cells were studied in hybrid mice of genotype (C57BL x C3H)F1 following treatment with specific cannabinoids. In the subacute series, mice were treated for 5 consecutive days with delta 9 tetrahydrocannabinol (THC), cannabinol or cannabidiol at a dose of 10 mg/kg, the percentage of micronuclei in cannabinoid-treated mice was 3- to 5-fold greater than in the dimethyl sulfoxide controls. In the acute series, polychromatic erythrocytes were scored after a single exposure. In one acute series there was an approximately twofold increase in the incidence of micronuclei in the cannabinoid-treated mice; in the other acute series of cannabinoid-treated animals the micronuclei values were as high as 6 times the control values. Interaction between dose and frequency of exposure was assessed for THC; the number of micronuclei was affected by THC dosage, but not by frequency of exposure. Further confirmation of nuclear aberrations was obtained from assessment of bone marrow mitosis. In this limited study of mitotic cells the incidence of metaphase aberrations in cannabinoid-treated animals was 5-7 times greater than in controls. PMID- 6252565 TI - Diltiazem: lack of myocardial beta-adrenergic receptor-binding capacity. AB - It has been suggested that the mechanism of action of the calcium blocker diltiazem (DZ) is via beta-receptor blockade. In order to test this hypothesis, the effects of DZ on the competitive binding of 3H-dihydroalprenolol (3H-DHA) to myocardial beta-receptors were evaluated and compared to those of a known beta receptor agonist. Preliminary validation studies indicate that binding sites for 3H-DHA exhibit stereospecificity for isoproterenol (IP) (l-IP>d-IP) and show greater affinity for l-epinephrine compared to l-norepinephrine. In order to test the binding capacity of DZ to beta-adrenergic receptors, binding-concentration relationships were constructed for 3H-DHA (3--60 nM) in the presence of no drugs, l-IP (10(-4) M), or DZ (2.2 x 10(-6) M). 3H-DHA binding was significantly inhibited over the entire concentration range by 1-IP but was unaffected by the other conditions. This study was repeated using two different concentrations of DZ (2.2 x 10(-5) and 2.2 x 10(-7) M) with a similar lack of inhibition of 3H-DHA binding. These data indicate that DZ does not bind to myocardial beta-receptors and, therefore, does not appear to act via a beta-receptor-blocking activity. PMID- 6252566 TI - Actinic effects of light and biological implications. PMID- 6252567 TI - Herpes simplex virus produces larger plaques when assayed on ultraviolet irradiated CV1 cells. PMID- 6252568 TI - [New drugs with cardiotonic activity I. Chemistry and pharmacology of the cardiotonic active principle of Annona squasmosa L. (author's transl)]. PMID- 6252569 TI - Enzymatic responses to skin flap elevation following a delay procedure. AB - Alterations in enzyme activities of glucose metabolism were determined in the distal portion of the skin flaps of guinea pigs elevated following 3, 7, 14, or 21 days of the delay period. Hexokinase, pyruvate kinase, lactate dehydrogenase, and glucose 6-phosphate dehydrogenase activities were increased during the delay period, whereas isocitrate and malate dehydrogenases exhibited little alteration. Increases in glycolytic enzyme activities observed during the delay procedure were diminished in the flaps elevated during initial 3 days of the delay period, but were maintained or increased further in the flaps elevated at 7 to 21 days. Despite high levels of enzyme activities during the early period of the delay, the flaps elevated during this period exhibited partial necrosis with a low glucose level and decreased enzyme activities. It is concluded that tissue glucose level and its utilization are crucial factors for flap survival. PMID- 6252571 TI - Clinical trials with a new intravenous liposoluble contrast material for computed tomography of the liver and spleen. AB - Ten patients with disseminated cancer were given intravenous injections of 0.2 ml/kg (40 mg l/kg) of the experimental contrast material EOE 13. Ct scans of the liver and spleen were taken prior to and 30 minutes after contrast infusion. Visualization of the liver was significantly improved in 5, moderately improved in 3, and not appreciably improved in 2. The spleen showed an obvious increase in density in all cases. No significant toxicity was encountered: untoward side effects consisted of fever, headaches, foul metallic taste, and weakness for a short period. Four patients had no side effects, and 2 experienced only abnormal taste sensation. Further experimental and clinical work is needed before the advantages and safety of this contrast material can be documented. PMID- 6252570 TI - The hepatitis B virus. PMID- 6252572 TI - Antivirals 1980--an update. PMID- 6252574 TI - Dissociation of aldosterone and prostaglandin biosynthesis in the rat adrenal glomerulosa. AB - The relationship between aldosterone production and prosta-glandin E2 synthesis was evaluated using the responses of isolated rat adrenal glomerulosa cells to angiotensin II, ACTH and potassium. Simultaneous PGE2 and aldosterone measurements were made during timed incubations with these stimuli, and in incubations with arachidonic acid, meclofenamate, indomethacin, and aminoglutethamide. PGE2 and aldosterone production were assessed by radioimmunoassay. We were not able to demonstrate stimulation of PGE2 by angiotensin II, ACTH, or potassium despite significant increments in aldosterone production with these stimuli. Arachidonic acid enhanced PGE2 synthesis, but had no effect on aldosterone realease. Indomethacin and meclofenamate inhibited aldosterone secretion. Aminoglutethimide depressed aldosterone production, but had little effect on PGE2 levels in the media. These studies demonstrate that dienoic prostaglandins play no direct role in aldosterone production stimulated by angiotensin II, ACTH, or potassium in rat adrenal glomerulosa cells. Since inhibitors of cyclo-oxygenase decreased aldosterone synthesis, it is possible that fatty acids other than arachidonic acid may be cyclo-oxygenated to products which regulate aldosterone production. PMID- 6252573 TI - On the multiplicity of platelet prostaglandin receptors. I. Evaluation of competitive antagonism by aggregometry. AB - Methods for the evaluation of competitive interactions at receptors associated with platelet activation and inhibition using aggregometry of human PRP have been developed. The evidence supports the suggestion that PGE1 and PGI2 share a common receptor for inhibition of platelet reactivity, but only a portion (if any) of the aggregation stimulation associated with PGE2 is the result of PGE2 binding (without efficacy) to this receptor. PGE2 (at .3-20 microM) is an effective antagonist of PGE1, PGI2, and PGD2 producing a shift of about one order of magnitude in the IC50-values obtained from complete aggregation inhibition dose response curves. The antagonism of PGD2 inhibition is particularly notable, 80 nM PGE2 levels are detectable. This and other actions of PGE2 indicate another platelet receptor for PGE2. PGE1 acts at both the PGE2 and PGI2 receptor. Other substances showing PGI2-like actions only at high doses (1-30 microM), display additive responses with PGI2 indicative of decreased affinity for the I2/E1 receptor and the absence of PGE2-like aggregation stimulation activity. PGI2 methyl ester has intrinsic inhibitory action not associated with in situ ester hydrolysis. The methyl ester is dissaggregatory showing particular specificity for inhibition of release and second wave aggregation. PMID- 6252575 TI - Post-conceptional induction of menses with a single vaginal suppository of (15S) 15-methyl prostaglandin F2 alpha methyl ester. AB - The induction of post-conceptional menses needs a technically simple method which would avoid instrumentation of the uterus. One possible method investigated in this study is the abortifacient effect of a single dose long-acting vaginal suppository containing 3.0 mg of (15S)-15-methyl prostaglandin F2 alpha methyl ester. Pregnancy was terminated successfully in 13 of the 14 subjects. Two successful patients required curettage for prolonged bleeding and retained products of conception. Prolonged vaginal bleeding and the uncertainty of endpoints with particular reference to human chorionic gonadotropin (HCG) constitute the major problem with this non-invasive method, and are discussed in the light of the data obtained. PMID- 6252576 TI - Effect of prostaglandins on ornithine decarboxylase activity in the testis of immature rat. AB - Intratesticular injection of prostaglandin E2 (PGE2) and F2 alpha (PGF2 alpha) caused stimulation of ornithine decarboxylase (ODC) activity in the testis of immature rats. PGE2 at a dose of 10 microgram per testis was maximally effective 2 hours after the injection. Dibutyryl cyclic AMP (cAMP) and 1 methyl, 3-isobutyl xanthine (MIX), a phosphodiesterase inhibitor, also stimulated ODC activity. Simultaneous injection of PGE2 and FSH or LH caused additional stimulation of ODC activity. Similarly injection of PGE2 in addition to cAMP or MIX also caused increased stimulation of ODC. Indomethacin (IM, 60 microgram/testis) inhibited LH, FSH or cAMP induced ODC activity. However, IM at the same dose inhibited the synthesis of total proteins. These results suggest that PGE2 and PGF2 alpha stimulate the activity of ODC. The action of prostaglandins may be independent of the action of gonadotropic hormones. cAMP appears to mediate the action of prostaglandins in the testis of rat. PMID- 6252577 TI - [R factor in Salmonella strains isolated from urban sewage to be used in agriculture]. PMID- 6252578 TI - [Acute diarrhea caused by rotavirus: various clinical aspects]. PMID- 6252579 TI - [Ultrasonics in the diagnosis of primary and metastatic hepatic tumors]. PMID- 6252580 TI - Behavioral and electrocortical effects after intrastriatal cefazolin in rats are antagonized by drugs enhancing GABA-ergic transmission. AB - Cefazolin, a semisynthetic cephalosporin, reported to reproduce in several animal species an experimental model of epilepsy, was microinjected into the head of the caudate nucleus in rats. The effects on behavior, electrocortical activity and the antagonism by GABA receptor agonists and GABA-transaminase activity inhibitors were studied. Cefazolin given into the III cerbral ventricle produced an intense pattern of behavioral and locomotor stimulation culminating into several episodes of wild-running crisis, myoclonic jerks of the limbs and in some occasions generalized clonic seizures, these effects lasting over 2 h. At the same time bursts of electrocortical high-voltage spikes followed bu intermittent high-voltage single spikes were recorded. Similarly cefazolin, given into the caudate nucleus produced contralateral circling, an increase locomotor activity, myoclonic jerks of contralateral limbs, intense stereotyped behavior and occasionally generalized clonic convulsions. In addition postural changes consisting in tonic contralateral head-neck deviation were observed. This picture was accompanied by epileptic electrocortical changes, i.e. high-voltage spikes, spike-waves complexes, recruiting polyspikes. The subsequent intraventricular or intrastriatal infusion of GABA, GABOB, muscimol or of GABA-transaminase inhibitors, ethanolamine-o-sulphate and GABA-vinyl-GABA was able to antagonize clinical and electrocortical changes evoked by cefazolin. In conclusion, the present results suggest that cefazolin motor and electrocortical effects are due to an impairment of GABA-ergic transmission. PMID- 6252581 TI - Immunological modification of adriamycin cardiotoxicity. AB - Adriamycin-specific antibody has been shown to increase the survival of mice receiving an acute cardiotoxic dose of adriamycin. The concentrations of adriamycin in heart tissue were reduced and those in tumor elevated for more than 2 days in animals that received the antibody. The adriamycin-specific antibody prevented and reversed adriamycin inhibition of cardiac microsomal Na-K ATPase. PMID- 6252582 TI - The uterotrophic effect of delta 9 THC in ovariectomized rats and mice. AB - We have reanalyzed the statistics on uterine weights used by Virgo in his article, The Estrogenicity of Delta-9-Tetrahydrocannabinol (THC): THC Neither Blocks nor Induces Ovum Implantation, nor does it Effect Uterine Growth, which appeared in Res. Comm. Chem. Path. and Pharmacol. 25:65-77 (1979). The reanalysis shows that administration of 3 and 6 mg/kg delta 9 THC to ovariectomized mice results in highly significant (P < .002; P < .0001 respectively) increases in uterine weights. These data are in accord with the uterotrophic effect of delta 9 THC observed in ovariectomized rats. PMID- 6252583 TI - The uterotrophic effect of delta-9-tetrahydrocannabinol in ovariectomized rats and mice. PMID- 6252584 TI - Role of catecholamines in the genesis of arrhythmias. AB - Catecholamines play a major role in the induction of cardiac rhythm disorders. The effects of catecholamines are caused by activation of beta-receptors in the heart and appear to be mediated by the cyclic AMP/protein kinase system. Increased rate of spontaneous diastolic depolarization of cardiac fibers on exposure to endogenous or exogenous catecholamine activity leads to tachyarrhythmias. Because of non-uniform distribution of sympathetic nerve endings, activation of the sympathetic nerve system may result in non-uniform reduction in the refractory period leading to re-entrant excitation. Under abnormal conditions myocardium may become more sensitive to catecholamines. In ischemia, sympathetic stimulation causes more local differences in refractory period and a greater tendency to fibrillate. Following acute coronary ligation there is a direct relationship between rhythm disturbance and levels of myocardial catecholamines. Catecholamines not only cause arrhythmia but also contribute to the development of digitalis-induced arrhythmias. The role of catecholamines in the genesis of certain cardiac arrhythmias is further supported by the fact that beta-blocking drugs which antagonize sympathetic activity are effective for treating various types of acute arrhythmias and for prevention of recurrent arrhythmias. PMID- 6252585 TI - Catecholamine/cyclic AMP/Ca2+ induces arrhythmias in the healthy pig heart. AB - Agents known to increase cAMP levels in the myocardium were infused subepicardially (focal infusion, 10 microliters/min) in healthy pigs (open chest). Noradrenaline (NA) (10(-5) M), adrenaline (10(-5) M), and isoproterenol (10(-6) M) (in 0.9% NaCl) induced arrhythmias infrequently, but in the presence of Ca2+ (2.5 X 10(-3) M CaCl2) they consistently induced arrhythmias--most commonly ventricular tachycardia--within 60 sec that were readily reversible on termination of infusion. N6,O2'-dibutyryl-cAMP (dbcAMP) and N6-monobutyryl-cAMP (mbcAMP) (5 X 10(-2) M each) produced arrhythmias lasting up to 1 hr with rather slow (up to 20 min) onset. Arrhythmias were induced by 8-Br-cAMP (5 X 10(-2) M) in the presence of inhibitor of cyclic nucleotide phosphodiesterase (3 X 10(-4) M Ro 7-2956) within 30 min. The NA/Ca2+ arrhythmias were abolished by isoptin, D 600, MnCl2 (each 10(-4) M) and beta adrenoceptor blockade (10(-5) M pindolol, 10( 4) propranolol; 10(-4) M D-propranolol was ineffective) but were not suppressed by tetrodotoxin (up to 10(-5) M). Arrhythmias induced by dbcAMP or mbcAMP were abolished by isoptin (10(-4) M) and MnCl2 (5 X 10(-4) M) but not propranolol (10( 4) M). The NA/Ca2+ arrhythmias were also abolished by carbamylcholine (10(-6) M). Acetylcholine (10(-4) M) was less effective. Arrhythmias were not precipitated by 0.9% NaCl, 2.5 X 10(-3) M CaCl2/0.9% NaCl, 5 X 10(-2) M N6-monobutyryl-2'-deoxy cAMP (deoxy-mbcAMP) or 10(-1) M sodium butyrate. Analysis of myocardial tissue obtained from the NA/Ca2+ infusion site showed that cAMP was increased when ventricular tachycardia ensued. We conclude that the catecholamine/cAMP/Ca2+ system may play an important role in the genesis of arrhythimas, possibly by inducing automaticity in ventricular fibers through slow Ca2+ channels PMID- 6252586 TI - Studies on myocardial mitochondria in ischemic dog hearts by electron spin resonance (ESR) spectrometry. AB - The free radical concentration of myocardial mitochondria from ischemic dog heart was studied by means of electron spin resonance (ESR) spectrometry, and the effects of acute free fatty acid (FFA) mobilization on the process of electron transport and oxidative phosphorylation of ischemic dog heart mitochondria were studied using free radical concentration in the state IV respiration of the myocardial mitochondria as the indicators. 1. The intensity of the ESR signal of mitochondria (g = 2.003) from intact dog heart was significantly increased in state IV compared to state I (state IV/state I = 2.01 +/- 0.18). On the other hand, in state III, the ESR intensity was markedly decreased compared to state IV (state III/state IV = 0.33 +/- 0.06). 2. The ESR intensity ratio of state IV/state I of the mitochondria from the ischemic area of 1-hr ischemic dog heart decreased remarkably compared to normal group. 3. The ESR intensity ratio of state IV/state I of the mitochondria isolated from the ischemic area of 2-hr ischemic dog heart was significantly lower than in the control. The ESR intensity ratio of state IV/state III of this group was significantly higher than in the control. 4. In ischemic heart with high plasma FFA, the free radical concentration in state IV respiration of the myocardial mitochondria was significantly decreased as compared to ischemic heart without high plasma FFA. These results suggest that the free radical concentration of myocardial mitochondria in respective respiratory states may be useful for evaluation of functional disturbance of oxidative phosphorylation and the electron transfer system in myocardial mitochondria in ischemic heart. Sudden and abnormal rise of plasma FFA seems to further facilitate the uncoupling of oxidative phosphorylation in the mitochondria of the ischemic portion of the heart. PMID- 6252587 TI - Oxidative phosphorylation in isolated canine myocardial mitochondria. Effects of in vitro volume dilution, lactate, phosphate, and calcium addition, and lactic acidosis. AB - Oxidative phosphorylation of isolated canine myocardial mitochondria was evaluated after exposure to different concentrations of phosphate (5-50 mM), lactate ion in excess (5-40 mM, pH 7.4), and calcium (50-200 microM), to lactic acidosis (pH 6.3), and to mitochondrial protein dilution (in vitro volume expansion) for 10 min to 8 hr. The influence of phosphate and lactate ion addition, lactic acidosis, and in vitro volume expansion on mitochondrial function were studied in the isolation medium (0.18 M KCl, 0.5% bovine serum albumin (BSA) with or without Tris-EDTA, pH 7.4) prior to evaluation of mitochondrial function in the assay medium (0.25 M sucrose, 10 mM Tris-HCl, and 10 mM inorganic phosphate, pH 7.4). The effect of calcium addition was assessed in the assay medium. The results of these studies demonstrate that each of these interventions detrimentally alters mitochondrial oxidative phosphorylative ability. The most severe mitochondrial function impairment resulted from phosphate (5-50 mM) or calcium (50 or 200 microM) addition, each of which decreased the rate of oxygen consumption by 40% or greater. The mitochondrial functional alterations resulting from the interventions that were studied persisted after their removal, but the detrimental effect of phosphate addition and in vitro volume expansion was partially corrected by the addition of cytochrome c. The data are consistent with the possibility that each of these interventions is capaable of altering mitochondrial function but suggest that phosphate and calcium ion accumulation exert the most important detrimental effect on oxidative phosphsorylation in isolated canine cardiac mitochondria. PMID- 6252588 TI - Effect of propranolol on cyclic nucleotides of ischemic dog heart. AB - The effects of ischemic and beta-blocker on myocardial cyclic nucleotides (cyclic AMP and cyclic GMP) of dogs were studied. The concentration of cyclic AMP in both infarcted and noninfarcted area 60 min after the ligation of the proximal part of the left anterior descending coronary artery to significantly higher than in sham operated control animals. The concentration of cyclic GMP in infarcted area is also significantly elevated compared with control 15 min after the ligation. The cAMP/cGMP (A/G) ratio in the infarcted group was also elevated at 60 min and returned to control level after 5 hr. When propranolol was given, the concentration of cyclic AMP of both infarcted and noninfarcted area remained at control level. In propranolol-treated animals, the concentration of cyclic GMP in both infarcted and noninfarcted area increased significantly compared with control at 15 min and 60 min. The A/G ratio was also decreased below control level after the administration of propranolol. These results suggest that the stability of the ischemic cardiac muscle was enhanced by the administration of beta-blockers. PMID- 6252589 TI - The heart and diabetes. Vascular and metabolic aspects. AB - The metabolic changes in the heart--increased glycogen, triglycerides, and cyclic AMP, and decreased ATP and creatine phosphate--indicate that diabetes is a generalized disorder of cellular metabolism. The summarized observations provide additional biochemical reasons for early detection and treatment of patients with diabetes mellitus. Cognizance of three metabolic events are relevant to the treatment of the diabetic patient during acute cardiac events such as myocardial infarction. PMID- 6252590 TI - [Collagenase in human liver cirrhosis. Presence of collagenase linked to acid soluble collagen in normal and cirrhotic livers (author's transl)]. PMID- 6252592 TI - [Study of the diagnostic significance of the serum IgE level in patients with bronchial asthma]. AB - The serum level of IgE was determined in 59 patients (of whom 36 had atopic asthma, 15 had non-atopic asthma, and 8 had various other pneumopathies with a bronchospastic component). A radioimmunological method was used. The data obtained show that the average values for IgE are high in atopic asthma (796 +/- 161 I.U. per ml). The highest values were of 4.000 I.U. per ml. The average value is clearly different from that found in non-atopic asthmatic patients (185 +/- 30 I.U. per ml), as well as from that recorded in the other patients (260 +/- 76 I.U. per ml), an indication that an assay of the serum level of the type of bronchial asthma. With regard to the di-sodium cromoglycate treatment it was demonstrated that this does not produce signficant changes in the concentration of serum IgE, and it is not possible to foresee, on the basis of the initial level of reagins, what the results of the application of this drug will ultimately be. PMID- 6252591 TI - Angiotensin stimulation of the central nervous system. PMID- 6252594 TI - [Suppurative bronchopneumopathies in aged persons]. PMID- 6252593 TI - [Sources of infection as indicators of tuberculosis endemy]. AB - An analysis is made of cases of pulmonary tuberculosis that have been confirmed bacteriologically, as well as from the point of view of the incidence, of the prevalence and of the dynamics of the contaminating reservior. The generally favourable evolution of these indices is stressed evidencing the great danger of contamination of new cases before these patients are detected. The necessity is also stressed of a continuous improvement in the case-finding and diagnostic activity. PMID- 6252595 TI - [Aspects of the incidence, temporary work incapacity and disability due to tuberculosis in the Galati district]. PMID- 6252596 TI - [Seneca oil]. PMID- 6252597 TI - [Bronchopulmonary cancer as a public health problem]. PMID- 6252598 TI - Late results of preventive chemotherapy in persons with fibrotic lesions of the lung ; benefit, cost and risk (from the IUAT isoniazid prophylaxis trial). PMID- 6252600 TI - [Study of the changes in resistive pulmonary work after respiratory exercise therapy]. PMID- 6252599 TI - [Early failures of chemotherapy in pulmonary tuberculosis in adults]. PMID- 6252601 TI - Initial SEM observations of Herpes simplex virus infected chicken chorioallantoic membranes. AB - Chorioallantoic membranes (CAMs) of 10 day old embryonated chicken eggs were experimentally infected with types 1 and 2 Herpes simplex virus (HSV) and observed by scanning electron microscopy. This preliminary report examined CAMs at time periods ranging from 30 minutes to 24 hours post-infection. Samples also were taken for transmission electron microscopy to correlate topographic alterations with ultrastructural changes. Uninfected control CAMs, throughout the study, consisted of a homogeneous population of flattened chorionic ectodermal cells whose surface were covered with uniformly distributed microvilli of varying lengths and fairly constant diameter. At thirty minutes post infection, irrespective of infecting herpes type, microvilli were markedly decreased in numbers with those remaining showing noted blunting. Later stages of infection with type 1 HSV strains showed a cytopathic process consisting of a generalized rounding of individual cells and the presence of cells apparently containing multilobulated nuclei. CAMs infected with type 2 strains demonstrated a more focal spread of infection and the presence of intranuclear filamentous structures by transmission electron microscopy. PMID- 6252602 TI - Specimen damage considerations in biological microprobe analysis. AB - In many biological materials radiation damage limits the resolution of the microanalytical measurement. To provide some perspective regarding the relative merits of different experimental arrangements, the dose to the specimen may be calculated using a simple model. While electron and proton probe X-ray microanalysis are found to involve heavy doses to the specimen, X-ray fluorescence, performed with a polarized, monochromatic X-ray probe, is the least destructive for the analysis of medium to heavy elements. For light elements (Z less than or equal to 20), electron energy loss spectroscopy or X-ray absorption microanalysis involve the lowest dose in most applications. Other advantages and limitations of the various techniques are also summarized. PMID- 6252603 TI - [The incidence of antibodies against hepatitis A virus in various age groups in the Basle population 1978-79]. AB - In a study on the prevalence of hepatitis A virus (HAV) exposure among the Basel population in 1978/79, 763 sera matched for age were tested for HAV antibodies by radioimmunassay (HAVAB). Sera of patients with a recent history of liver disease were not included. The results show that the prevalence of HAV antibodies increases with age, a situation similar to that in poliomyelitis before vaccination. The prevalence of HAV antibodies rises from 15% in the 11-20 year age group to 90% in the over-71 age group. The fall in HAV exposure with decreasing age is attributed to a decline in infections due to improvements in hygienic standards during this century, and especially since World War II. The average prevalence of HAV antibodies found in this study is 52%. The results are partly influenced by the high proportion of subjects originating from foreign countries among the population investigated. PMID- 6252604 TI - [Burkitt's lymphoma in a Swiss patient]. AB - In summer 1978, Burkitt lymphoma was diagnosed in a 23 year old Swiss male. A brief report on this patient appears justified for the following reasons: (1) Burkitt lymphoma is very rarely diagnosed in Switzerland. (2) The tumor cells of this patient could be established as a cell line. They have now been subpassaged in vitro for over 9 months. (3) In contrast to the majority of non-African Burkitt lymphomas, these tumor cells produce small amounts of Epstein-Barr virus. PMID- 6252605 TI - [Etiopathogenesis of colorectal carcinomas]. AB - There are a small group of colonic carcinomas of known etiology and large group of unknown etiology. In the latter group epidemiology, metabolic epidemiology, and animal experiments suggest a correlation between the fat content of the diet and the incidence of colonic carcinoma. Burkitt's postulate of a protective value of high fibre intake receives backing from 3 epidemiological studies from Israel, Scandinavia, and San Francisco. PMID- 6252606 TI - NMR opens a new window into the body. The use of nuclear magnetic resonance for medical diagnosis hovers on the brink of practical application. PMID- 6252607 TI - Adrenocorticotropic hormone may be transported directly from the pituitary to the brain. AB - Experiments were designed to test the hypothesis that pituitary hormones may be delivered directly to the brain. Concentrations of adrenocorticotropic hormone (ACTH) in the plasma were determined in blood samles obtained simultaneously from the carotid artery, the sagittal sinus, and the jugular vein of three awake sheep. Seizures were induced electrically to stimulate ACTH secretion, and at precise intervals thereafter several simultaneous comparisons were made in each animal. In many of the post-seizure comparisons, the ACTH plasma concentrations within the sagital sinus exceeded those within the carotid artery as well as those within the jugular vein, indicating that this hormone was released from the pituitary and carried directly through capillary beds of brain to the venous blood within the sagittal sinus. The experiment was repeated in one hypophysectomized sheep and, in this animal, ACTH concentration in the plasma was reduced, but that in the sagittal sinus still was elevated after the seizure, an indication that some ACTH (or ACTH-like material) was released from the brain itself. PMID- 6252608 TI - [Is thyroid extract necessary in the treatment of obesity? (author's transl)]. AB - In 273 patients divided in 12 classes according to the weight, plasma T3, T4 and TSH, thyroid response to TSH and pituitary response to TRF are the same in each category. There is no reason of value for giving thyroid extract in the treatment of obesity. PMID- 6252609 TI - [Diffuse myalgias. A series of 210 cases (author's transl)]. AB - 210 cases of diffuse myalgias are analysed. Among them two groups of very near frequency can be distinguished. The first group (100 cases) concerns mainly inflammatory myalgias. In the second group (110 cases) no organic aetiology is found. They appear as purely "functional", frequent manifestations of an anxious and/or depressive condition. Their evolution is often chronic and refractory to therapeutics; the diagnosis is frequently misappreciated. PMID- 6252610 TI - [Analysis of loco-regional control rate, metastatic remission and survival in 178 breast cancer patients treated by radical modified mastectomy and post-operative irradiation (author's transl)]. AB - 178 cases of post-operative irradiation for breast cancer (145 T1, T2, T3 and 33 T4) are analyzed. According to the surgical procedure there are 146 cases of radical modified mastectomy (Patey) and 32 cases of radical mastectomy (Halsted). The axillary status reveals 50% of involved nodes, but radiotherapy has been systematic on chest wall and supra-clavicular, parasternal, axillary lymph nodes areas. Loco-regional failures are only situated on chest wall (3,9%) and in the supraclavicular area (1,7%). The five year actuarial rate of locoregional control is 93% and 98% if we exclude 7 locoregional failures contemporaneous or consecutive to a metastatic evolution. The five year actuarial rate of metastatic remission for patients with negative axillary nodes (N-) is 83% against 55% for N+ (p < 0,001). The five year actuarial survival rate is 92% (N-) and 64% (N+) (p < 0,001). We discuss about indications of selective irradiation of chest wall and parasternal area for patients with negative axillary nodes and also about post operative immuno-suppression, and chronology of chemotherapy. PMID- 6252612 TI - [Cytomegalovirus-induced lasting fever in previously healthy adults. Nine cases (author's transl)]. PMID- 6252611 TI - [Moya-Moya syndrome and renal artery stenosis (author's transl)]. PMID- 6252613 TI - [Ultrasonography investigation of mammary calcifications (author's transl)]. AB - Ultrasonography recordings in 140 patients with breast cancer, 119 with cystic mastopathy, and 299 with benign mammary tumours showed that calcifications are rarely demonstrated, and that diagnosis is not affected to any degree when they are present. Ultrasonography should be used for examination of the breast following the three traditional clinical, radiological, and cytological investigations. False negatives (7.9% of cancers) and false positives (4.2% of fibro-adenomas) are easily corrected from radiological and cytological findings which are still essential for the diagnosis of most mammary affections. Ultrasonography, however, enables an appreciable reduction in biopsy requests to be made in less than 6% of cases of atypical microcalcification in benign mammary lesions. PMID- 6252614 TI - [Results of a protocol for etiologic diagnosis of pneumopathies on immunosuppressed children (author's transl)]. AB - A protocol for etiologic diagnosis has been used on 40 immuno suppressed children with pulmonary infiltrate. The purpose of this protocol is to permit an early etiologic diagnosis, concomitant infections by several pathogen agents being frequently seen. An endobronchial brushing is first performed; the results being obtained between 24 to 48 hours. If the results are negative and the patient's condition worsens we propose an open lung biopsy. Thus pathogenic agent has been established in 24 cases, in 17 cases by endobronchial brushing, in 3 cases by open lung biopsy and in 2 cases by endobronchial brushing and open lung biopsy. In 3 cases several opportunistic organisms were responsible of the pneumopathy. Pneumocystis carinii is the most often established (19 cases); it was also present in one out of 6 post mortem examinations. In 14 cases the pneumopathy occured in children treated for acute leukemia; Pneumocystis was the organism responsible in 6 of them; the evolution was favorable in 13 of the 14 cases. One patient died from a pulmonary infection by the measles virus. PMID- 6252615 TI - [Collar-stud tumour composed of combined neurilemmona and haemangioma elements. Clinicopathological study of one case with mediastinal and intraspinal localization (author's transl)]. AB - A mediastinal and intraspinal collar-stud tumour in a 77 year-old-woman is reported. The orginality of this study comes from the histologic findings of a combined neurilemmoma and angioma. The authors also include a brief review of literature and clinicopathological and histogenetic comments, about these combined tumours. PMID- 6252616 TI - [Diffuse hemangiomas of the skin and gastrointestinal tract. A case of blue rubber bleb naevus (author's transl)]. AB - The authors report the case of a 33-year-old patient with 109 skin hemangiomas of the blue rubber bleb naevus type, accompanied by angiomas of the mucosa of the gastrointestinal tract. Bleeding of the angiomas caused anemia. This case was apparently sporadic. The authors recall the clinical, histological and ultrastructural features of this rare disorder. Histology can help to differentiate BRBN from glomangioma. PMID- 6252617 TI - [Mixed cryoglobulinaemia and benign monoclonal gammopathy in Sjogren's syndrome (author's transl)]. AB - The authors report a case of Sjogren's syndrome associated with Raynaud phenomenon and mixed IgM-IgG cryoglobulinaemia. Three years after the onset of this association:--Immunoelectrophoresis of the serum showed a monoclonal IgM (lambda) protein, --the level of the mixed IgM-IgG cryoglobulinaemia had increased from 28 mcg/ml up to 12 mg/ml and its IgM component was monoclonal (lambda) with anti-IgG activity. Search for amyloidosis and for a malignant lymphoma was negative. Such an association of a benign monoclonal gammopathy, mixed cryoglobulinaemia and Sjogren's Syndrome has only exceptionally been reported in the literature. PMID- 6252618 TI - [Trouble of liver function in polymyalgia rheumatica (author's transl)]. AB - The possible existence of liver function disease such as cholestasis during temporal arteritis or polymyalgia rheumatica has been recently discovered. Two cases are reported of cholestasis without jaundice during polymyalgia rheumatica. The alterations most frequently observed are the elevation of the alcalin phosphatases, 5' nucleotidases, gamma G.T. and the retention of BSP. The syndrome disappears by treatment as well as the rheumatologic disease. It seems to be interesting to diagnose polymyalgia rheumatica through this trouble of liver funcion. PMID- 6252619 TI - [Appendicular endometriosis. Report of one case (author's transl)]. AB - The authors studied, in one case, the signs of appendicular endometriosis. This endometriosis is discovered either through the symptoms occuring in the right iliac fossa, or during a surgical operation, usually gynecological. They emphasize the easy treatment by appendicectomy. PMID- 6252620 TI - [Kawasaki disease (mucocutaneous lymph node syndrome). Description of a case (author's transl)]. AB - The authors relate a case of mucocutaneous lymph node syndrome, first described by Kawasaki in 1967, including a fever, lasting more than five days, an erythematous rash, cervical lymphadenitis, with a usually good prognosis. One to two percent of patients die suddenly of cardiac failure with coronary aneurysm and thrombosis. Microscopically coronary arteries such as other arteries show inflammation with dilaceration of the vascular wall without necrosis. These pathologic features suggest a relationship to infantile periarteritis nodosa. PMID- 6252621 TI - [The jejuno-gastric invaginations after partial gastrectomy. General survey of literature concerning a personal observation (author's transl)]. AB - The authors relate an observation of a postgastrectomic jejuno-gastric invagination. On this occasion they make a general survey of the literature and analyze the 113 cases published up to now. The frequencies of apparition of this complication are much variable, from a few days up to several decades and the clinical symptoms are chronic or acute. They insist on the interest granted by the radiologic and endoscopic examinations for the diagnosis and on the proposed treatment aiming a twofold goal: reduce the invagination and avoid the recurrence. PMID- 6252622 TI - [Growth hormone: mode of action on different varieties of cartilage (author's transl)]. PMID- 6252623 TI - [Introduction to the study of hemostasis in cirrhotic patients (author's transl)]. AB - Any diffuse lesion of the liver induces permanent hypercoagulation with subsequent permanent lysis and possible consumption or DIVC/Hemostasis depends on two distinct mechanisms: the platelets, whose functional activity is more important than numbers, and the coagulolytic equilibrium of the plasma. Apart from the activating and inhibiting enzymes of coagulation and lysis, the lungs and liver play an important role. The lungs filter and then determine lysis of the corpuscular agglomerates. The liver produces epuration of the activated factors and prothrombinase, as well as the plasminogen activator. Except in extremely severe cases, however, these functions are rarely involved. Investigations must be complete and include a test of platelet aggregation, a TEG on total blood to analyze whole coagulation, and tests for consumption and lysis. Coagulation and bleeding time tests are of great value during severe hemorrhagic attacks. Pathological examination should evaluate the condition of the vascular state and, more particularly, the presence of fibrin thrombi with the appropriate methods. PMID- 6252624 TI - [The menopause and its problems (author's transl)]. AB - The first problem is one of definition : the menopause coincides in time with the arrival of anovulation and the disappearance of the menses ; the premenopause is characterised by irregularity of the cycles and the secretion of estrogens by the internal theca ; the perimenopause covers the entire period of the premenopause and the menopause itself. The second aspect considered is social and demographic : the average age seems to be rising (nowadays 52 years of age) but this is more an impression than a certainty ; in 1972, it was estimated that there were three million women undergoing the perimenopause in France ; finally, it would be easier for women to come through the menopause, if, at that age, they were entrusted with social responsibilities to fill their leisure time. A final problem relates to the understanding of the physiopathological factors involved. The growing insensitivity of the ovary and the consequent hormonal changes are well known, but the hypothalamo-pituitary axis remains intact and it is beginning to be thought that complex catecholamine interactions may be involved at this level. The complexity of hormonal balances and the varied effects of hormones and their derivatives suggest that much might be gained from studying the possibility of estrogen therapy. PMID- 6252625 TI - [Menopausal risk factors (author's transl)]. AB - Menopausal disorders coincide with the onset of luteal insufficiency and the resulting relative hyperestrogenism. At this stage the risks to be assessed are mainly related to a worsening of the menstrual syndrome (heaviness of the legs, abdominal distention, water retention, mastodynia, depressive syndrome), cycle changes, or various genital types of hemorrhage requiring investigation for detection of a possible fibroma, hyperplasia, endometriosis, or genital cancer. Once the menopause is settled a reduction in estrogen levels comes with reactive increases in FSM and LM levels, and the principal risk is the development of a cancer. The role of endogenous (obesity, diabetes, Stein-Leventhal, adenomatous hyperplasia) or exogenous (prolonged estrogen therapy alone) estrogens has to be evaluated in endometrial cancer. Cancer of the vulva also appears to be more frequent in menopausal women (natural or artificial), as well as cervical cancer and cancer of the breast. There is an apparent increase in cardiovascular risks in untreated menopausal women, but this is still discussed, as to the benefits of estrogen therapy. PMID- 6252626 TI - [Vasomotor sudden flushes (author's transl)]. AB - The most typical disorder encountered during the menopause is the sudden flush, but the etiopathogenicity of these disorders is still a matter of hypotheses only. Increased levels of FSH and LH have been evoked ; recent cutaneous temperature studies have demonstrated a significant increase in LH but not of FSH, E1, and E2, during sudden flushes. The degree and rapidity of estradiol level variations have also been suggested as relevant factors. Current opinion conduces to be favoured with the involvement of gonadotropins, catecholamines, and indolamines, and perhaps prostaglandins at the hypothalamic level. Whatever the cause may be, vasomotor flushes are present in 55 to 75 % of menopausal women, and may be accompanied with sudoral crises, palpitations, or lipothymia. Women with a harmonious family life are better able to endure these disorders, treatment being most necessary when they result from a greatest disorder. Therapy is essentially estrogen therapy (after exclusion of cancer), progestogens, or veralipride, a non hormonal agent which produces 80 % of positive results, without apparently the disadvantage of estrogen therapy. PMID- 6252627 TI - [Post-menopausal osteoporosis : physiopathology and therapy (author's transl)]. AB - Though directly related to the estrogen levels deficiency during the menopause, post-menopausal osteoporosis, which represents 80 % of presenile osteoporosis cases, are very unequally affecting women. A rich bone system and high residual blood estrogen levels are two essential factors for preventing this invalidating affection, especially if the woman continues to lead an active physical life and to take a diet which includes a balanced intake of calcium. Women "at risk" will benefit from administration of estrogen progestogen therapy as early as possible after the menopause onset, as long as no contra-indications to this treatment will take place and that it is administered under close supervision. PMID- 6252628 TI - [The menopause and the skin (author's transl)]. AB - It is currently admitted that the skin and its appendages plays an important part in steroid metabolism, especially in genital androgens, estrogens and progestogens. This activity produces the cutaneous changes sometimes associated with the premenopause period : facial hyper-seborrhea, seborrhea of the scalp, loss of scalp hairs, increaed pilosity on the cheeks and upper lip, whether they occur spontaneously or after hormonal treatment. Following the menopause-onset a progressive decreases in hair growth, can be observed, especially in the axillary and pubic regions, with occasional diffuse alopecia, increase in degeneration of elastic tissue, and atrophy of the vaginal mucosa, in fact as some changes appearing in the skin show correlations with the hormonal changes, others appear to be more closely related to aging of the skin. Thus, hormonal therapy will not be able to treat efficiently all these disorders. PMID- 6252629 TI - [Should the menopause be treated ? When and how? (author's transl)]. AB - The premenopausal period is characterized by a luteal insufficiency which may be associated with spaniomenorrhea, mastodynia, and more rarely, vasomotor flushes. Therapy is based on the administration of progestogens which, taken from the 10the to the 25th day of the menstrual period act as affective contraceptive. After an artificial menopause by surgical castration, increased FSH levels are noted, together with a rapid reduction of plasma estrogen levels, and a secondary rise in LH levels. Therapy consists in giving ethinyl-estradiol for 25 days a month, together with a progestogen from the 15th to the 25th day of the cycle, after excluding cancer of the ovary, uterus, or breast. The natural menopause is often associated with vasomotor flushes, psychofunctional disorders, and occasionally with vulvovaginal atrophy. Usual therapy is based on the administration of estrogens or sequential estrogen-progestogen treatment. Close, regular medical watching is necessary, however, because of the risk breast or endometrical cancer, and vascular or lipid disorders. PMID- 6252630 TI - [Test of pituitary adrenal restraining with IV dexamethasone in the diagnosis of Cushing's syndrome (author's transl)]. AB - The authors report a pituitary adrenal retraining test, using a 4 h IV infusion of dexamethasone phosphate (4 mg). Plasma cortisol is measured before and at the end of the infusion. The results allow a good discrimination between Cushing's disease (bilateral adrenal hyperplasia : 9 cases) and Cushing's syndrome of tumorous origin (adrenal tumors 7 cases, ectopic ACTH syndrome 3 cases, hypophyseal adrenomas 2 cases), only bilateral adrenal hyperplasia cases are lowering significantly. PMID- 6252631 TI - [Periodic paralysis. Histological, histochemical and ultrastructural studies in five cases (author's transl)]. AB - Muscle changed found in five patients with periodic paralysis are described. Three patients had familial hypokaliemic paralysis, one had familial periodic paralysis with hyperkaliemia, and one had periodic attacks of muscular weakness with thyrotoxicosis. According to the stage in the clinical course at which biopsy was performed, several pathological patterns are described. Vacuolization was the main feature in the early stages of periodic paralysis. Later in the clinical course, tubular aggregates were the characteristic findings. In addition, degenerative changes of the muscle fibres were found in patient exhibiting a permanent myopathic condition. In thyrotoxic periodic paralysis, the longer the clinical course, the more severe the changes appeared to be. Possible mechanisms leading to such structural abnormalities remain in question. PMID- 6252632 TI - [Hypertension and oral contraceptive therapy (author's transl)]. AB - Twenty-nine patients, either taking oral contraceptives or having stopped since less than six months, were referred for hypertension. Three conditions have to be satisfied in order to incriminate with certainty the responsibility of oral contraceptives inducing hypertension : normal blood pressure before therapy (included pregnancies), normalization of blood pressure in a delay of three months at most after the discontinuation, no other etiology of hypertension. The small number of hypertensions really induced by oral contraceptives is opposed with the great number of hypertension (essential or not) revealed by oral contraceptives. PMID- 6252634 TI - [Blood pressures in children and adolescents. An epidemiological study on 6 391 school children in a French circumscription (author's tranls)]. AB - Distribution characteristics of blood pressure (BP) by age and sex were studied in a school population of 6 391 children aged 6-18 years. BP distributions were according to a Gaussian curve tending towards the higher values. Mean BP increased with age according to linear curve. Systolic BP (SBP) was higher in boys from 14 and diastolic BP (DBP) after 16. An over all prevalence of 3,1 % systolic and 2,2 % diastolic hypertension (BP greater than or equal to 2 DS) was detected. Subjects with hypertension must be annually examined ; only those with BP greater than or equal to 3 DS must be completely investigated for etiological purpose. SBP and DBP were strongly connected. Scales give opportunity to BP follow-up during growth and promise a better understanding of early hypertension. PMID- 6252633 TI - [Endocarditis due to Hemophilus para-influenzae associated with mitral valve prolapses (author's transl)]. AB - The authors report one observation of endocarditis due to Hemophilus para influenzae associated with mitral valve prolapsus. This germ is difficult to isolate and is found late in cultures using standard techniques. The dicovery of germs resistant to ampicillin requires the search for the presence of a betalactamase. When resistant germs are found, the antibiotic of choice is chloramphenicol or cefamandole. This type of endocarditis different from the others on account of the risk major of embolism (60-85 p. 100) which justifies valve replacement when the echography reveals persistant vegetations. PMID- 6252635 TI - [Oral contraceptives :misunderstood etiology of erythema nodosum (author's transl)]. AB - The cutaneous side effects of oral contraceptives are uncommon but their manifestations are many and varied. Erythema nodosum is rare, it is typical but the associated signs are few and do not permit the etiological diagnosis. The latter rests mainly on the spontaneous disappearance of the symptomatology when the prescription of oral contraceptivae is discontinued and on the relapse on resumption of the retake. The physiopathology, much controversed, causes immunological disorders on the predisposed individual. Only stopping oral contraceptives intake brings about the cure. PMID- 6252636 TI - [Palliative intubation under fibre-endoscopic control in cancer of the esophagus and cardia (24 cases) (author's transl)]. AB - Positioning of the intra-esophageal prothesis under fibre-endoscopic control sets up a simple and effective method as a palliative treatment of dysphagia in patients with esophageal cancers unable to take advantage of curative treatment. It makes the short survival of those patients more comfortable with a low mortality rate. An X-Ray-therapy may be associated. PMID- 6252637 TI - [Diarrhea in children due to a new viral agent]. PMID- 6252638 TI - [Pathogenesis of salmonellosis]. PMID- 6252639 TI - [Catechol estrogens]. AB - Hydroxylation of oestrogens in the 2 or 4 positions leads to the formation of catechol oestrogens. These compounds are physiologically active in animals, especially in the control of gonadotropin secretion. Physiological activity can be ascribed to either an oestrogenic action or interaction with the catecholaminergic systems. These compounds are also formed in human subjects. Surprisingly high levels are found in the urine. The peri-ovulatory peak in urinary catechol oestrogen excretion is compatible with a role for these compounds in the control of gonadotropin secretion. PMID- 6252640 TI - Serum angiotensin-converting enzyme in sarcoidosis. AB - Serum angiotensin-converting enzyme (SACE) activity was measured in 29 patients with sarcoidosis, 51 reference subjects, 7 patients with active tuberculosis and 8 patients with other lung diseases. SACE activity was increased in 93% of the patients with sarcoidosis as compared with the reference subjects. Patients with active tuberculosis and other lung diseases did not have increased SACE activity. PMID- 6252641 TI - A comparison of oestrogen-progestogen with clonidine in the climacteric syndrome. AB - Twenty-three cases of the climacteric syndrome were analysed in a double-blind study comparing the effect of conjugated equine oestrogen (Premarin) and medrogestone (Colpro) with clonidine (Dixarit) on various clinical parameters. The treatment lasted 20 weeks. Statistical analysis of the results indictaed that opposed oestrogen therapy was effective in reducing hot flushes (P < 0,05) whereas clonidine was not. The other variables tested did not attain statistical significance. PMID- 6252642 TI - Mediastinal masses. PMID- 6252643 TI - Carcinoma of the lung. PMID- 6252644 TI - Benign tumors of the lung and bronchus. AB - Benign tumors of the lung and bronchus are a heterogeneous group of lesions that usually present as asymptomatic, solitary, peripheral lung nodules or, less commonly, as endobronchial lesions causing obstructive symptoms. All endobronchial lesions should be removed surgically to alleviate symptoms and to prevent destruction of distal lung tissue. Parenchymal lesions may present challenging problems in clinical diagnosis and management. Most patients will ultimately require thoracotomy for histologic confirmation of benignity. It is probable that newer diagnostic procedures will allow a more accurate nonoperative diagnosis in certain patients in the near future. At the present time, expeditious limited thoracotomy affords a safe, rapid, and effective treatment for patients with a benign tumor of the lung or bronchus. PMID- 6252645 TI - Opportunistic infections of the lung. PMID- 6252646 TI - Liposarcoma of the lower extremity. AB - Twenty patients with primary liposarcoma of the lower extremity were treated over a 25-year period. The adequacy of the initial surgical procedure and histological grade of malignancy both influenced survival rates. In addition local recurrence was noted only in patients who had undergone "inadequate" initial excision. Inguinal lymph nodes were uninvolved by tumor in all cases. In general, patients with liposarcomas of myxoid and/or round cell type survived for long periods of time. However, even patients with myxoid lesions occasionally exhibited evidence of early blood-borne metastases. This study suggests an important relationship between an inadequate primary resection, local recurrence, and eventual retroperitoneal spread. In the majority of cases, this may have resulted from failure to control the primary distal extremity tumor, with subsequent contiguous spread of metastases into the ipsilateral retroperitoneal space. If feasible, radical soft part resection should be performed as the primary surgical therapy of these neoplasms. Tumors contiguous to the knee or ankle joint should be treated by primary amputation. Failure to control local disease may result in blood-borne dissemination or local spread along musculoaponeurotic planes to involve proximal groin or retroperitoneal space. PMID- 6252647 TI - [The importance of bulk in the genesis and treatment of disease (author's transl)]. PMID- 6252648 TI - Coronavirus infection in a litter of pups. AB - An outbreak of a coronavirus infection in a litter of 10-week-old poodle pups from a commercial kennel is described. Coronavirus-like particles were demonstrated by electron microscopy in the intestinal contents and in the colonic mucosa. Treponemas and campylobacters were excreted in great numbers in the faeces. The gastrointestinal disturbances were complicated by hepatic and renal degeneration and severe bronchopneumonia. PMID- 6252649 TI - Egg transmission of egg drop syndrome 1976 virus in fowl. AB - Egg transmission of egg drop syndrome 1976 virus (BC14 virus) in fowl was demonstrated in the second and third week after experimental infection. Eggs of BC14 virus infected hens were incubated weekly after disinfection with formaline gas. After 18 days of incubation, eggs with live embryos were homogenized. This egg material was fed to adult hens, housed in isolators. Seroconversion in these birds demonstrated egg transmission. It is suggested that egg transmission occurs as a result of viremia. PMID- 6252650 TI - [Vaccination of cattle against respiratory disease caused by virus infection (author's transl)]. AB - Studies on the epizootiology of respiratory viruses in herds of cattle showed that infection by bovine respiratory syncytial (BRS) virus was a major cause of bovine respiratory disease in calves. Moreover, of IBR virus infection associated with respiratory symptoms were observed in the Netherlands since the Spring of 1974. Outbreaks of IBR virus infections occur throughout the Netherlands today. Initially, outbreaks ran a course marked by the typical symptoms of haemorhagic rhinitis, observed particularly in cows. Today, IBR virus infections have become enzootic on several farms, the majority of infections in young cattle being accompanied by respiratory symptoms that are identified as being due to IBR virus infection. Other virus infections that may cause respiratory disease, parainfluenza virus 3, adeno viruses and bovine virus diarrhoea (BVD) virus, were found to be enzootic in most herds in the Netherlands. However, there is no definite correlation between the occurrence of these infections and clinical symptoms. The use of vaccines against these virus infections is not advisable in the present situation. A vaccine against BRS virus infections is commerically available. Immunization by this vaccine against the pulmonary symptoms of BRS virus infection should be verified by a field trial. Unvaccinated control groups of calves should be included. In the experience of the present author, the immunity produced by this vaccine cannot prevent infection by the field strain of BRS virus. Postvaccination reactions were observed within seven days after vaccination with this vaccine in some cases. These were attributable to non cytopathogenic strains of BVD virus, contaminating some batches of this commerical vaccine. PMID- 6252651 TI - [Neonatal diarrhoea in calves (author's transl)]. PMID- 6252652 TI - [Border disease: a persistent virus infection in sheep (author's transl)]. AB - Border disease (BD) is a congenital infection of sheep characterised by still birth, abortion and the birth of weak lambs with nervous symptoms and sometimes an abnormally hairy birthcoat. The lambs are almost constantly trembling or shaking, they often have an erratic gait and in severe cases are unable to rise. The nervous signs are due to a defective myelinogensis of the central nervous system and tend to disappear at a later age. Many affected lambs die shortly after birth and those which survive usually show retarded growth. The disease is caused by a virus which is closely related to the virus of bovine virus diarrhoea (BVD). The virus may be isolated from every organ and is excreted with saliva, nasal discharge, urine and faeces. Clinically the diagnosis can be made with high probability when nervous signs and hairy birthcoat are both present. Laboratory diagnosis is based on the detection of antigen by immunofluorescence or virus isolation. In addition ewes of BD-affected lambs usually possess antibodies against BVD-virus. In some lambs, an immune response starts during prenatal life, others show a transient or lasting low level response at a later age, whereas still others remained serologically negative for at least 2 1/2 years. Asymptomatic virus carriers occur among lambs as well as among adult sheep. The persistently infected animals are continously shedding virus and thus maintain the infection in the flock. PMID- 6252653 TI - [Transmission and immune response in bovine enzootic leukosis (author's transl)]. AB - The causative agent of enzootic bovine leukosis (EBL) is an oncogenic RNA virus named bonvine leukosis virus (BLV). At present, instead of bovine leukemia, the name bovine leukosis is preferentially used to avoid an erroneous association with leucaemia in man. In all European Community Countries the serological diagnosis of EBL has gradually replaced hematology. A number of these serological techniques are available to-date. In the Central Veterinary Institute in Rotterdam the agar gel immunodiffusion technique, the FAT and the ELISA are used as diagnostical tools. Based on own experiments it is provisionally concluded that BLV shedding via faeces and urine does not occur. Saliva has been found infective in three out of fourteen cases (21 per cent). There is no evidence of transmission of BLV in the sperm. Prostate fluid and sperm from seven experimentally infected bulls did not contain neither BLV antigen nor antibodies to BLV. Five calves born from five cows which had been naturally served by the mentioned bulls did not show sero conversion after an observation period of one year. The authors recommend to use in AI only sperm form bulls which are negative for antibodies to BVL. Preferentially other cattle at the same farm-enterprise should be serologically tested with negative results within three months before shipment of the sperm. The humoral and cellular immunological status of leucotic cattle are examined by the application of pig erythrocytes, tetanus toxoid, Bordetella- and Aujeszky vaccine. The seroloical reactions of leucotic cattle did not differ significantly from those of the "normal' controls. By contrast the cutaneous tuberculine reaction following administration of Mycobacterium microtii was significantly more obvious in the leucotic animals as compared to the controls. PMID- 6252654 TI - [Maedi and maedi control (author's transl)]. AB - Maedi/visna is a chronic progressive interstitial pneumonia of sheep caused by a persistent infection with a retrovirus. Approximately thirty per cent of the sheep population in the Netherlands carries antibodies to maedi virus. An experimental eradication scheme based upon serological testing with ELISA and culling of reactors every six months was started, recently. Initially, 353 (25.4 per cent) reactors were identified among 1391 sheep in sixteen flocks, whereas the second test, six months later, showed 130/1111(11.7 per cent) reactors. On 11 other farms with high infection level 382 lambs were separated from their dams immediately after birth, ovine colostrum deprived and artificially reared. The lambs were serotested at 6 months of age and 2/382 (0.5 per cent) were found positive, while naturally reared lambs on the same farms scored 39 per cent positive. PMID- 6252655 TI - [Recent studies on Aujesky's dissease in pigs and cattle (author's transl)]. AB - A standardized test model for Aujeszky disease (AD) vaccines in pigs is described. The first two vaccines tested, a modified live virus (MLV) vaccine and an inactivated vaccine, failed to produce satisfactory results. The inactivated vaccine induced a short-lived, but clear-cut increase in body temperature in some of the vaccinated pigs; the MLV-vaccine was shown to spread. Complete protection against intranasal (i.n.) challenge was not achieved with either vaccine in five month-old pigs that had been vaccinated once or even twice two to three months previously. However, the vaccinated pigs were less severely affected, and for shorter periods, than were the control animals; losses from death did not occur. In the control groups, at least thirty per cent died, the average growth of the remainder was arrested for more than three weeks. The mean period of arrested growth after challenge of pigs vaccinated once with the MLV-vaccine was slightly shorter than that following a single vaccination with the inactivated vaccine: 5.8 and 9.5 days respectively. The average virus excretion of vaccinated pigs after challenge was less and was not as protracted as in unvaccinated controls. In pigs from sows hyperimmunized with the inactivated vaccine, maternal antibodies afforded partial protection against i.n. challenge at the age of two months. However, five-month-old pigs were fully susceptible, although most of them continued to show low levels of neutralizing antibody. The average virus excretion after challenge in the two age-groups was comparable with that in control pigs. Cattle were effectively protected by vaccination with the inactivated vaccine against i.n. challenge with AD-virus. It is recommended to vaccinate "threatened" cattle twice, for instance in the autumn when they are removed from the pastures for indoor housing. The possibility that temperature reactions may occur should be taken into account. PMID- 6252656 TI - [Developments in foot-and-mouth disease (FMD) vaccine production (author's transl)]. AB - Cattle in the Netherlands are annually vaccinated with MDV-vaccine which is prepared from FMD-virus grown in 'surviving' bovine lingual epithelium. This 'Frenkel production system' which was developed in the Central Veterinary Institute during the forties and early fifties is still fully operative under practically the same conditions as those by the late Dr. Frenkel. However, recent experiments show that the method can be made more productive among others by regulating the PH. Particulary in non-European countries FMD-vaccines are prepared from virus produced in suspension cultures of a Baby-Hamster kidney (BHK) cell line. In the present author's variant of the system, virus is produced in growing BHK cells. This is possible as antibodies were removed from the serum in the culture medium by pretreatment of the serum with PEG. Virus was partly purified and concentrated by a precipation-filtration-elution (PFE) process: virus is precipated with PEG, the precipated virus is collected (with 'filter aid') on a filter and eluted by pumping a buffer solution through the filter cake. Adequate protection of cattle was obtained with Al(OH)3-vaccines, which were prepared from these AEI-inactivated antigens. For the vaccination of pigs, satisfactory results were obtained with double-oil emulsion (W/O/W) vaccines prepared from these antigens. For long-term storage below -70 degrees C, antigen was highly concentrated (200 x) by a second PFE cycle. Purified antigen was obtained, which, if incorporated in double oil emulsion vaccines, has so far induced satisfactory protection of pigs. By this method, a strategic stock of concentrated inactivated antigen may be built up in order to make it possible to produce large amounts of vaccine in a last.minute operation. PMID- 6252657 TI - [Recent developments in the preparation of vaccines (author's transl)]. AB - Recent developments in biochemistry, immunology and organic chemistry suggest two new methods of producing vaccines. These new procedures which may perhaps be adopted in the future, are described. It is shown that, in the case of foot- and mouth disease, viral protein 1 (VP1) rather than the complete virus may be used in a vaccine. This protein could be produced by genetic manipulation. The isolated antigenic site responsible for inducing neutralizing anti-bodies might also be utilized in a vaccine. This antigenic site which probably is not any longer than ten amino acids, may be produced by organic chemical synthesis once its sequence is known. Both in the case of VP1 and in that of the antigenic site, the immunogenities of these products have to be increased as VP1 is less immunogenic than a comparable amount of complete virus, whereas the antigenic site presumably is not immunogenic at all. These new vaccines are safer and possibly cheaper to produce than the classical ones are. Moreover vaccines against viral diseases could be produced, which cannot be obtained by classical methods. PMID- 6252658 TI - [Studies on the resistance of fattening pigs following inoculation with various vaccines at an age of four to nine weeks (author's transl)]. PMID- 6252659 TI - Studies on sulfhydryl radioprotectors with low toxicities. PMID- 6252660 TI - Altered metabolism of progesterone by hepatic microsomes from rats following dietary exposure to polybrominated biphenyls. PMID- 6252661 TI - Effect of 2,5-Hexanedione on lipid biosynthesis in sciatic nerve and brain of the rat. PMID- 6252663 TI - An analysis of the toxicity of hydroquinone on central synaptic transmission. PMID- 6252662 TI - Inhibition of sciatic nerve sterologenesis in hexacarbon-induced distal axonopathy in the rat. PMID- 6252664 TI - Cytotoxicity of food dyes on cultured fetal rat hepatocytes. PMID- 6252665 TI - Polybrominated biphenyl toxicosis in swine: Effects on some aspects of the immune system in lactating sows and their offspring. PMID- 6252666 TI - [Indication and results of radiation therapy in the treatment of astrocytomas (author's transl)]. AB - The course of 77 patients with well-differentiated or anaplastic astrocytoma after treatment with resection and radiotherapy or radiotherapy after biopsy during the years 1954--1978 at the University hospital at Zurich is analyzed. The ten-year survival rate in patients with well-differentiated astrocytoma is about 30%. About 15% of the patients with anaplastic astrocytoma are living after 5 years, but there is no 10-year survivor in this group. Patients with mixed glioma (astrocytoma plus oligodendroglioma) show the same survival rate as patients with well-differentiated astrocytoma. Analysis of tumor dose and the size of the irradiated volume shows only in patients with anaplastic astrocytoma a trend to better survival rate after doses of at least 5000 rd in 5 weeks and irradiation fields larger than 200 cm2. In accordance with published reports, the survival rate in patients with gemistocytic astrocytoma is lower than in the other cases. PMID- 6252667 TI - [Radiation therapy of the renal tumor in children (author's transl)]. AB - Close cooperation of pediatric surgeons and pediatric oncologists with radiotherapists, using coordinated treatment schedules conformable to the stage of the disease, and combining tumor nephrectomy, postoperative irradiation and the treatment with AMD and Vincristine, has increased the 3-year survival rate from 27% (13 of 49) up to 67% (14 of 21) for children with Wilm's tumor. PMID- 6252668 TI - Viral hepatitis markers in Soviet and American blood donors. PMID- 6252669 TI - Epidemiology of acute gastroenteritis in early childhood in Kenya: aetiological agents. AB - In a case-control study of 36 infants and children admitted to Kenyatta National Hospital with acute gastroenteritis and an equal number of age and sex-matched controls, rotavirus was found to be the major aetiological agents; 39% of the 36 children had evidence of rotavirus infection as opposed to 2 (6%) in controls. Six Shigella species were isolated from the test group and none from the control. No significant difference was found between children with diarrhoea and controls wth regard to frequency of isolation of enteropathogenic and enterotoxigenic E. coli, Salmonella species and enteroviruses. Mixed infections occurred between rotaviruses and other enteropathogens. None of the 17 serum pairs obtained from children with diarrhoea showed a significant titre rise to complement-fixing adenovirus group antigen. PMID- 6252670 TI - I11-defined somatic symptoms in a South Indian rural clinic. Some preliminary clinical observations. AB - A detailed physical and psychiatric examination was carried out on 125 patients presenting with vague illdefined sensory symptoms, at a South Indian rural primary care clinic. Among these 94 cases were found to have a predominantly sensory peripheral neuropathy, 19 cases had evidence of other medical illnesses, and only 12 cases could be categorised as being functional. The large number of cases of peripheral neuropathy in a South Indian village is probably nutritional and resembles the clinical pattern of the burning feet syndrome. The significance of the presentation of these cases with vague somatic and psychological symptoms to psychiatric epidemiology is stressed. PMID- 6252671 TI - Helminths in the induction of cancer: Opisthorchis viverrini, Clonorchis sinensis and cholangiocarcinoma. AB - Opisthorchis and Clonorchis parasitize the bile ducts of millions of persons in the Far East. The most important aspect of infection with these flukes is their ability to initiate cancer. Numerous studies have shown these flukes to occur in association with cholangiocarcinoma far more frequently than can be explained by chance. Experimental studies in animals have confirmed the carcinogenic potential of these parasites. Although the pathogenesis remains unclear, the initial carcinogenic event is probably a function of the length and severity of infection, the host's immune response, and such variables as ingestion of dietary carcinogens. PMID- 6252672 TI - Interrelations of PTH, cAMP, creatinine and uric acid in nephrectomized patients under DNA or PTH application. AB - Patients with reduced renal mass (i.e., nephrectomized) and slightly decreased renal clearance (70-80%) have been treated by 4 g DNA to study uricosuria. Prompt or prolonged renal excretion of uric acid and creatinine have been observed with indirect effects on parathyroid secretion. Urinary cAMP, however, failed to correlate to the change of parathyroid function. Reversely, PTH injection significantly increases uricosuria suggesting interrelated secretion of uric acid and cAMP of the proximal tubules. In some respects this model can be used to investigate increased DNA metabolism and parathyroid function. PMID- 6252673 TI - The direct measurement of inhibitory capacity to crystal growth of calcium oxalate in undiluted urine and in other inhibitor containing solutions. AB - This paper describes a simple method to measure the capacity of undiluted urine and of other inhibitor containing solutions (PPi and EHDP) to protect a given mass of calcium oxalate crystals from growth. The method has also been used to determine relative urinary saturation with respect to calcium oxalate. It is based on titration with oxalate and measures the critical changes of concentration necessary to reach saturation or to induce crystal growth. From these changes inhibitory capacity as well as the level of urinary saturation can be calculated in terms of differences of concentration products. The use of the methods at present available to measure urinary oxalate are thereby avoided. In order to compare the results from different urines without the need for cumbersome calculations of activity products we have introduced a saturation inhibition ratio. PMID- 6252674 TI - Comparison of computed tomography and ultrasound in abdominal staging of renal cancer. AB - The relative accuracy of computed tomography (CT) and ultrasound in abdominal staging of renal cancer was determined in 22 patients. CT is capable of detecting tumor invasion of perinephric fat and adjacent muscles, which cannot usually be shown by ultrasound. While both CT and ultrasound demonstrate venous and retroperitoneal tumor extension, CT is more reliable since bowel gas not infrequently obscures the retroperitoneum on ultrasonic scanning. However, ultrasound will often provide valuable information; and whenever a solid renal mass is detected by echography using prone scans, abdominal scans should be obtained for staging pruposes. PMID- 6252675 TI - [Some mechanisms of papaverine and trental action in patients with acute arterial obstruction]. AB - A comparative study of the effect of trental and papaverin upon the systemic and peripheral blood circulation was carried out in patients with acute arterial obstruction of the lower extremities due to embolism. The advantage of trental over papaverin is shown convincingly. Injection of papaverin results in the improvement in 38% of cases. Trental improved microcirculation in the diseased extremity in all the examined patients without substantial changes in the regional microhemodynamics and systemic circulation. PMID- 6252676 TI - [Bilateral carotid chemodectoma]. PMID- 6252677 TI - [The occurrence of antibodies to the glycoprotein antigen (gp70) of the enzootic leukemia virus in a leukemic herd]. AB - The serological examination of 175 head of cattle in a herd suffering from leucosis included the study of the occurrence of antibodies to the glycoprotein antigen (gp70) of the virus of enzootic leucosis (BLV). At the same time, these antibodies were studied, as occurring in the F1 generation of the progeneis of 51 positive and 38 negative cows. The results demonstrate two important facts: increasing age brings about a higher percentage of animals having precipitating antibodies in the leucosis-affected herd; the other important finding is that the positive reaction of a cow has no significant influence on the occurrence of the antibodies in the progeny. It was found that under the actual conditions of the mentioned herd, the horizontal transmission of enzootic leucosis was predominant and that precipitating antibodies were detected by the immunodiffusion method in animals at the age from 9 to 12 months. It is desirable from the viewpoint of diagnostics and eradication of enzootic bovine leucosis to apply with utmost consistency the serological methods of examination and individual diagnostics. There is no reason for destroying whole families of animals in which the disease occurred, because no genetically conditioned occurrence of enzootic leucosis was demonstrated in the progenies of cows suffering from the disease. These facts should be respected in amending the instructions for controlling enzootic bovine leucosis. PMID- 6252678 TI - The effects of Clostridium perfringens type A enterotoxin in Shetland ponies- clinical, morphologic and clinicopathologic changes. AB - Severe abdominal pain, classic colic signs and hemorrhagic gastro-entero cecocolitis were induced in three conventional Shetland ponies by intravenous injection with Clostridium perfringens Type A enterotoxin. Histological examination showed marked congestion, edema and hemorrhage of the large and small intestine and sloughing of the tips of the intestinal villi. Marked vacuolar degeneration of hepatocytes with dilatation of the spaces of Disse also was found. Clinical changes consisted of severe hypoglycemia, markedly increased aspartate aminotransferase levels and leukopenia that occurred rapidly. PMID- 6252679 TI - Cytoplasmic crystalloids in the ovary of a woolly monkey. PMID- 6252680 TI - Cytoplasmic crystalloids in the ovary of a woolly monkey. PMID- 6252681 TI - [Angiography in nephroblastoma metastases to the liver in children]. PMID- 6252682 TI - Inhibition of nuclear migration of wild-type SV40 tumor antigen by a transport defective mutant of SV40-adenovirus 7 hybrid virus. PMID- 6252683 TI - Biochemical characterization of nuclear and cytoplasmic forms of SV40 tumor antigens encoded by parental and transport-detective mutant SV40-adenovirus 7 hybrid viruses. PMID- 6252684 TI - Characterization of Moloney murine leukemia and sarcoma viruses separated by isokinetic gradient centrifugation. PMID- 6252686 TI - Evidence for repair of ultraviolet light-damaged herpes virus in human fibroblasts by a recombination mechanism. PMID- 6252685 TI - Chemiluminescence: an early event in the interaction of Sendai and influenza viruses with mouse spleen cells. I. The role of the envelope glycoproteins in the stimulation of chemiluminescence. PMID- 6252687 TI - Sensitivity to gamma rays of avian sarcoma and murine leukemia viruses. PMID- 6252688 TI - [Effect of adrenalectomy on the enzymatic activity in thin kidney slices and homogenates]. AB - A method of "thin slices" was developed for estimation of enzymatic activities in cells, in which relationship between structure elements was maintained and the cells were readily permeable for substrates. Activities of Na, K-ATPase and succinate dehydrogenase were markedly higher in thin slices than in homogenates; activities of choline esterase and lactate dehydrogenase were of the same value in both tissue preparations. As compared with controls, adrenalectomy caused a decrease in Na, K-ATPase activity in the tissue slices, activities of succinate- and lactate dehydrogenases were unaltered and the choline esterase activity was increased. Comparison of the enzymatic activities in homogenates and thin slices indicates that some contradictions in data on the effect of the adrenal cortex hormones on the activity of the enzymes involved in the ion transport porcesses are due mainly to unadequateness of the methods used. PMID- 6252690 TI - [Mechanism of the activating action of noradrenaline on rat cerebral cortex Na, K ATPase]. AB - Effect of noradrenaline on kinetics of Na, K-ATPase activation in rat brain cortex was studied using ATP as a substrate and Na+ or K+ ions as cofactors. Noradrenaline (5 x 10(-5) M) increased the activating effect of ATP and Mg2+ as well as that of Na+ and K+. In presence of ATP and Mg2+ the hormone activated ATPase by the mixed type, and in response to Na+, K+ addition--by the non competitive type. Noradrenaline appears to cause the conformational alterations in Na, K-ATPase molecule, which change the kinetics of the enzyme activation by ATP and the ions. PMID- 6252689 TI - [Change in the cyclic nucleotide system components in neurogenic myopathies]. AB - Values of Kdiss of the "protein kinase-cAMP" complex were decreased 2-6-fold in muscular tissue of patients with neurogenic myopathies. An increase in affinity of the protein kinase to cAMP correlated with the severity of the disease. Alteration in the cAMP-sGMP ratio, due to decrease in cGMP content, was found in patients with side amyotrophic sclerosis. PMID- 6252691 TI - [Isolation and properties of 3 Clostridium histolyticum collagenases]. AB - The collagenases (I, II and III) have been obtained in a highly purified state from fresh cultural medium of Clostridium histolyticum. The collagenases were similar in their properties to clostridiopeptidase A. The three enzymes differed in their molecular weights, isoelectric points and in some chemical properties. Collagenase II exhibited the most potent hydrolytic activity. Its collagenolytic activity was two-fold higher and the peptidase activity was twenty-fold higher as compared with that of collagenase I. All the three enzymes were inactive towards azocasein and were inhibited by EDTA and cysteine. PMID- 6252693 TI - [Rotavirus gastroenteritis in children (a review of the literature)]. PMID- 6252692 TI - [Changes in prostaglandin systhetase activity in mouse tissues as affected by S [N-(3-aminopropyl)-2-aminoethyl] thiophosphoric acid]. AB - Effect of various concentrations of a radioprotector S-[N-(3 aminopropyl)-2 aminoethyl] thiophosphoric acid on the activity of prostaglandine synthetase was studied in mouse liver microsomes as well as in the soluble fractions of testicules and brain in vitro. The activity of prostaglandine synthetase was estimated by monitoring the formation of labelled PGF2 alpha and PGE2 from I-14C arachidonic acid. The radioprotector at concentration 1.66 mg/ml stimulated formation of PGF2 alpha in all the tissues studied. At the lower concentrations of the radioprotector only slight stimulation of the biosynthesis of prostaglandines in testicules was noted. No effect on their synthesis in the brain soluble fraction could be observed while in the liver microsomes it was inhibited. The radioprotective substance studied apparently affected the cyclooxygenase activity, which is a key enzyme in the prostaglandine-synthesizing system. PMID- 6252695 TI - [Steroid balance in breast cancers of varying histological structure]. AB - Patients with breast cancer in stage I--II of various histological structure showed varied hormonal disturbances. In adenocarcinoma a high level of classic estrogens or total phenolsteroids was noted. In low differentiated cancers (solid, scirrhus) the values of estrogens excretion were considerably lower, but, if correlated with other hormones (androsterone), a relative hyperestrogenization is observed. Scirrhous cancers are characterized by the increased 17-ketogenic steroids excretion. The character of hormonal disturbances concomitant with the predominant development of certain breast tumor structures (adenocarcinoma, solid cancer, scirrhus) is identical for the patients being in their reproductive and menopausal period. PMID- 6252694 TI - [Functional state of the hypophyseal-adrenal system in lung cancer]. AB - The results are reported on studies of the secretion of adrenocorticotropic (ACTH), somatotropic (STH) hormones and cortisol, using a standard set for in vitro diagnosis. A total of 66 patients aged 31--70 (64 males and 2 females) have been examined. Among these patients stage II was noted in 17, stage III--in 31, stage IV--in 18. In 19 of them a peripheral cancer and in 47--central cancer was detected. The data obtained indicate an increased basal level of ACTH, STH, cortisol which is directly dependent on the cancer process stage. The maximum increased level of these hormones was noted in low differentiated cancer of the lung. PMID- 6252696 TI - [Wilms' tumor in a 9-day-old infant]. PMID- 6252697 TI - [Isolation of the protein component of the soluble Tamiami virus antigen by using affinity chromatography on IgG-cellulose]. AB - IgG to Tamiami virus is covalently bound to metaaminobenzylcellulose by nitrogen coupling. An immune sorbent was prepared and used to treat the virus soluble antigen (SA); a protein responsible for the serological properties of SA was isolated. Electrophoretic analysis in polyacrylamide gel showed this protein to be a nucleocapsid protein of the virion. PMID- 6252699 TI - [Antibodies to rubella virus in the blood sera and in the synovial fluid of children with rheumatoid arthritis]. AB - Sera and synovial fluids from children with rheumatoid arthritis (RA) were examined for antibody to some viral and mycoplasmal antigens. Blood sera from the patients were found to have a selective excess of antibody to rubella virus as compared with the age norm. Antibody of this specificity was found in synovial fluids in titers significantly higher than those in the blood. Titers of other antibodies in the synovial fluids were, as a rule, slightly lower than in sera. In the time course of intercurrent respiratory diseases, despite the lack of rubella introduction into the wards, children with RA showed variations in the levels of antibody to rubella virus much more frequently than to other infectious agents. The foregoing data are discussed from the point of view of the etiological association of juvenile RA with rubella virus persistence. The antigen of the latter was found in snyovial membrane cells of 4 children by means of immunofluorescence procedure. PMID- 6252700 TI - [Results of vaccinating children against poliomyelitis according to the epidemic indices in the Dagestan ASSR in 1978]. PMID- 6252698 TI - [Detection of MMTV gp52 in C3H and C3Hf strain mice]. AB - Immunofluorescence in paraffine sections demonstrated the difference in expression of the membrane glycoprotein of mouse mammary tumor virus (gp52) in two mouse sublines: C3H and C3Hf. In the C3Hf the glycoprotein becomes detectable in the mammary gland in the second part of pregnancy while in C3H line mature females before pregnancy. No viral glycoprotein could be found in the spleen, liver, kidneys and other organs in males and females of the two sublines or in C3H embryos. PMID- 6252701 TI - [Species-specific flavivirus antigens for the indirect hemagglutination reaction]. PMID- 6252702 TI - [Antibodies against coxsackie, influenza and parainfluenza viruses in patients with symptoms of myocarditis]. PMID- 6252703 TI - [Effectiveness of acedist in the treatment of fascioliasis of sheep]. PMID- 6252704 TI - [Statistical evaluation of cytologically diagnosed pulmonary carcinoma (author's transl)]. AB - A statistical evaluation of bronchopulmonary carcinomas shows differences with regard to their location, types, incidence and cytological diagnosis in various materials. PMID- 6252705 TI - [Report on 198 malignant pulmonary diseases in 1975--therapy and results (author's transl)]. AB - A report is given on 198 patients with malignant pulmonary diseases, which were discovered in 1975. In the cases of primary carcinomas of the lung the stages and types of tumours are discussed. In the secondary carcinomas the kind and location of the metastases in the thoracic region and the primary tumours are listed. After a short description of the symptoms leading to hospitalisation and of the accompanying illnesses the kinds of therapy used are discussed in more detail and the results of a check-up at 1st January 1980 are given. PMID- 6252706 TI - Regulative influence of o-aminobenzoic acid (OABA) on the biosynthesis of nourseothricin in cultures of Streptomyces noursei JA 3890b. V. Effect of OABA on cytochrome levels and amino acid transport. AB - o-Aminobenzoic acid (OABA) known by its stimulatory effect on streptothricin biosynthesis by Streptomyces noursei JA 3890b was found to suppress specifically the formation of cytochrome a-type terminal oxidase while the levels of the b- and c-type cytochromes apparently remained unaffected. This change was coupled to decreased capacity of transport of u-14C-L-alanine and u-14C-L-glutamic acid into the mycelium, giving rise to delay of amino acid catabolism and decreased production of nitrogen catabolites within the cell. The above results provide supporting evidence for conjectures recently published by us concerning the control by nitrogen catabolites of the secondary metabolism of this strain. As a summary a scheme is proposed showing several hypothetic mechanisms by which nitrogen catabolite regulation of nourseothricin production could be accomplished. PMID- 6252707 TI - In vivo and in vitro recombination of lambda DNA in CaC12 transfection. AB - Using CaCl2 mediated transfection with Lambda DNA fragments, in vitro joining by ligase and in vivo recombination with helper phage DNA are effective systems for generating artificial recombinants. Recombination efficiencies are 20--30% in the in vitro and in vivo recombination systems. At 30 to 37 degree C T4 ligase mainly joins natural cohesive alpha ends, while at 12 degrees C the EcoRI-generated termini are preferentially ligated to form biologically active molecules, if the cloning vector alpha 401 is used, which has only one EcoRI target. The ligation products were characterized by gel electrophoresis and CaCl2 transfection. For in vivo recombination a new CaCl2 transfection system was developed, termed postinfection-dependent CaCl2 transfection system, which is based on the infection of recipient cells with helper phages after transfection. In marker rescue experiments using this method not only single but also double recombination occurred between two independent alpha DNA fragments and the helper phage DNA. PMID- 6252708 TI - [Protection of foreign DNA against host-controlled restriction in bacterial cells. II. Protection of pSF2124 plasmid by the gene function of bacteriophages T3 and T7]. AB - When restriction-active Escherichia coli cells (R+P1m+P1) are transformed with the pSF2124 plasmid, a common vector in experimental gene transfer, the efficiency of transformation (e.o.t.) is lowered by 2 orders of magnitude compared with restriction-negative (r-P1m-P1 or r-P1m+P1) recipient cells due to restriction of the pSF2124 DNA by endoR.EcoP1. Preinfection of r+P1m+P1 cells with UV-inactivated ocr+ phages (T3, T7, T3sam-) still able to express their early genes protects the plasmid DNA against restriction by endoR.EcoP1: The e.o.t. of r+P1m+P1 recipient cells with pSF2124 attains the same high value as that of r-m- cells. The specific role of the ocr+ gene function was demonstrated by the use of ocr- mutants (T3/R7, T7/D111): Preinfection with such phage mutants does not increase the e.o.t. of r+P1m+P1 cells. An unspecific e.o.t. alteration of restriction-negative (r-m-) recipient cells by ocr+ or ocr- phages was excluded. The ocr+ gene function can be exploited to protect pSF2124 against DNA restriction. The recipient cells survive the process of phage preinfection and transformation and stably replicate themselves as well as the plasmid DNA. PMID- 6252709 TI - Dihydroxyacetone kinase of methanol-assimilating yeast. I. Regulation of dihydroxyacetone kinase from Candida methylica in situ. AB - In order to investigate the control behaviour of dihydroxyacetone kinase of methanol-grown Candida methylica under nearly physiological conditions kinetic and regulatory studies were carried out in situ. Yeast cells were made permeable to substrate and reaction products by treatment with Triton X-100. Normal Michaelis-Menten kinetics resulted in dependence upon the dihydroxyacetone concentration, both at the pH optimum of 7.6 and near the physiological pH-value of 6.5. The Km obtained for dihydroxyacetone was 0.02 mM, independent of the pH value. The plots of dihydroxyacetone kinase activity as a function of the ATP concentration revealed complex kinetic characteristics with plateau regions. The maximum reaction rate was reached only after a lag time both at pH 7.6 and concentrations of ATP higher than 5 mM and at pH 6.5 and concentrations of ATP higher than 1.25 mM. Among a great number of tested metabolites no inhibitors of dihydroxyacetone kinase were found. Dihydroxyacetone kinase activity depending upon energy charge according to Atkinson exhibited curves of the U-type. These results and further data concerning the regulation of other enzymes obtained with C. methylica and other yeasts were the basis to propose a preliminary overall model of fine control of the carbon and energy metabolism of methanol-utilizing yeasts. PMID- 6252710 TI - Histo-chemical mapping of phosphomonoesterases in the gonads of Notopterus notopterus and Colisa fasciatus during different seasons. Part II. Adenosine triphosphatase and glucose-6-phosphatase. AB - Histochemical techniques described by McManus (1960) have been applied in the fishes, Notopterus notopterus and Colisa fasciatus, for the study of Glucose 60phosphatase and adenosine triphosphatase in the four stages of gonads in different seasons. It has been observed that the activity of adenosine triphosphatase is more intense in comparison to the activity of Glucose-6 phosphatase in all the stages i.e. I (immature), II (maturing), III (mature) and IV (spent) of the gonads in both the fishes. The general tendency of the adenosine triphosphatase and Glucose-6-phosphatase distribution in the gonads are much more remarkable in stage II in comparison to stage I, III and IV. The stage I seems to be the stage of synthesis of these enzymes. In stage III and IV, these enzymes show the tendency of declination with the time period. The possible role of these enzymes seems to be the transport of glucose across the cell membrane involving phosphorylation and dephosphorylation which depend on the different stages of gonad maturation. PMID- 6252711 TI - [Sacrificial profession - demand and method]. PMID- 6252712 TI - [Paramedical treatment methods. Endangering the patients through paramedical healing methods and magical components]. PMID- 6252713 TI - [Modern occultism and its roots]. PMID- 6252714 TI - [Multiple reticulohistiocytoma]. PMID- 6252715 TI - [Nutrient digestibility and N-balance after administration of an alpha glucosidase inhibitor to pigs]. PMID- 6252717 TI - [The importance of weeds for the transmission of Rhizoctonia solani Kuhn. IV. The role of weeds in the overwintering of the pathogen (author's transl)]. AB - In Model trials the overwintering of Rhizotonia solani Kuehn in different substrates with and without naturally infected plant materials has been studied. The results we obtained demonstrate that R. solani is able to overwinter like mycelium or sclerotia in sand and soil without organic debris. We observed a higher parasitic activity of the fungus in soil than in sand. The survival of the pathogen in soil is more promoted by addition of naturally infected roots of weeds than by burying of colonized potato tubers. PMID- 6252716 TI - [Effectiveness of symbiotic n2-fixation in leguminous plants, as affected by inoculation with rhizobia, by substrate, n-fertilizing, and 14c-sucrose application (author's transl)]. AB - Cultivation experiments (Mitscherlich-vessels, quartz sand, 15N-labelled soil, 15N-fertilizer) showed, that various strains of Rhizobium lupini (white and yellow lupines) and of Rhizobium leguminosarum (field beans and peas) induced a different N2-fixation of the inoculated plants, the most effective Rhizobium strains being 367a, Cz, T3, 271 (Rh. lupini), and Azotogen (Rh, leguminosarum). Yellow lupines and field bean plants were supplied with N2 from the air considerably better than white lupines and peas after inoculation with the most effective Rhizobium strains. Application of mineral N to the white lupines and peas not only substituted the inhibited N2-fixation, but increased N amounts in the plants. White lupines fixed more N2 under soil conditions than in quartz sand. An experiment with steam-sterilized and 15-labelled soil as a comparative substrate showed, that this finding was mainly caused by an additional Rhizobium infection from the soil. Contrary to field beans and yellow lupines which fix N2 up to ripeness, white lupines and peas finished N2-fixation in the time of flowering. Mineral-N applied at that time was an additional source of N for last named plants and they utilized it for production of higher protein yields. Continual spraying of white lupine plants with 14C-labelled sucrose solution after the time of flowering caused continuance of N2-fixation up to the stage of ripeness. It is assumed that the cause of this effect was the competition of growing seeds and nodules for the photosynthates. The supply of nodules was inadequate without external sucrose application. Mineral N inhibited the sucrose induced N2-fixation of white lupine nodules and their consumption of photosynthates. Consequently, the applied 14C was transported into seeds to a larger extent. The investigations allow the following conclusion: Effective N2 fixation requires nodules being a powerful sink for assimilates on the basis of a highly efficient photosynthetic system of the host plant. PMID- 6252718 TI - Replication of TBE and Langat viruses in cells from immune individuals. AB - The replication of TBE virus and Langat virus in cells of immune and non-immune individuals was compared in phytohemagglutinin (PHA)-stimulated and non-PHA stimulated cultures and also following infection with low and high infection multiplicity. Following infection of spleen cells from Langat-immune mice with Langat virus having a high infection multiplicity, higher virus replication rates than in non-immune cells were found to be present. Replication of Langat virus was generally superior to that of TBE virus. Virus replication was generally reduced by PHA stimulation of spleen cells. Langat virus did not replicate in human peripheral leukocytes. TBE virus replicated equally well in cells from a patient with TBE history and in cells from a non-immune person. PMID- 6252720 TI - Antioncogenic activity of influenza virus on polyoma virus induced renal and brain tumors in newborn Wistar rats. AB - Simultaneous inoculation of newborn Wistar rats with intact A/PR 8/34 (HON 1) influenza virus and the S.E. strain of polyoma virus resulted in significant reduction of the rates of both kidney sarcomas and brain tumors in comparison to controls given polyoma virus, only. This antioncogenic activity (AOA) of influenza virus was observed independently whether or not influenza and polyoma virus were injected on different sites or were inoculated as a combined vaccine. Ether-treated A/PR 8/34 influenza virus was found to have also AOA. However, in one experiment a significant AOA was demonstrated with respect to brain tumors, only, and not for the rate of renal sarcomas. In addition, the influenza strain A/Hong Kong/1/68 (H3N2) was found to have AOA. PMID- 6252719 TI - [Virus-specific IgM proof with routine serologic methods (author's transl)]. AB - By the use of a specific immunosorption to insoluble adsorbentia (controlled-pore glass, polystyrene particles) the separation of IgM and IgG is performed in serum specimens, which originate from patients presenting several virus infections (mumps, measles, cytomegalovirus, herpes simplex), for the virus-specific IgM proof with routine serologic methods (CFT, HIT, NT). The results are in a good agreement to them seen in the demonstration of significant titer rises to assure the diagnosis of acute mumps and measles infections by HIT rapidly. While the new technique is also successfully applied for the determination of neutralizing IgM and IgA antibodies to HSV, no sufficient results are available to detect CMV specific IgM antibodies by CFT compared to other methods (IFT, ELISA). PMID- 6252721 TI - [Antibodies to rotavirus in human milk (author's transl)]. AB - 116 human milk specimens taken from 36 women during the first 10 days after delivery were investigated for antibodies against rotavirus by crossimmunoelectrophoresis. Antibodies were detected in 37 specimens from 24 women, the antibody titers proved to be lower than the serum antibody titers. Antibody concentrations in the colostral and transitory milk samples declined continuously during the 10 days after delivery. Women with high serum antibody titers against rotavirus possessed antibodies in their colostrum more frequently than women with low antibody titers. There was no difference between the antibody titers in the sera of the women and the corresponding cord blood. PMID- 6252722 TI - Action of three species of Propionibacteria (P. granulosum, P. acnes, P. avidum) on experimental tumor systems in mice. AB - The antitumor activity of three different species of Propionibacteria (P. granulosum, P. avidum and P. acnes) against murine Sarcoma 180 and Moloney Sarcoma-Virus-induced tumor (MSV tumor) was investigated. All three Propionibacteria injected intraperitoneally or intratumorally in multiple doses of 1 mg per mouse appeared to be effective regarding the retardation of growth and the stimulation of regression of Sarcoma 180 in CFW mice. Moreover, the application of Propionibacteria significantly prolonged the survival of Sarcoma 180-bearing mice. No significant differences were found in antitumor effect against Sarcoma 180 between P. granulosum, P. Avidum and P. acnes, but in general, intratumoral injections of all three strains were more effective than intraperitoneal applications. All three strains of Propionibacteria were equally ineffective regarding the retardation of growth and the stimulation of regression of MSV tumors in adult NMRI mice, as assessed after intraperitoneal injections of P. granulosum, P. avidum or P. acnes (1 mg per mouse) 3 days prior to inoculation of virus particles. PMID- 6252723 TI - [Problems of maintaining hygienic and microbiological quality standards in the production of foodstuffs, particularly those of vegetable origin. Second report: Demands regarding hygiene and microbiology-theory is useless without practice (author's transl)]. AB - Many legal regulations exist on the hygienic-microbiological properties of food products. The 'Lander-Speiseeisverordnungen' (County Ice Cream Regulations), the 'Diat-Verordnung' (Dietary Regulation) and the 'Trinkwasser-Verordnung' (Regulation on Potable Water) are examples for the frequent inadequacies inherent in these regulations. Caution is indicated against any new proposals for the establishment of additional hygienic-microbiological regulations without sufficient practice-related reasoning unless a revision and improvement of inadequate, already existing regulations has been carried out. Practicable procedures have to be prepared not only to maintain the hygiene in Catering facilities, but also for the evaluation of food products and raw materials according to hygienic-microbiological criteria: Although commonly assumed, the 'Microbe Counts' alone are not sufficient for the determination of the hygienic conditions. Therefore, inspite of all the weak points inherent in quality control procedures - e. g. possible sick, co-workers, only random sample control of raw material supplies - such adapted systems (good manufacturing practice) have to be enforced with special emphasis on the economy of the control expenditure, interdisciplinary aspects, governmental control and consumer information. Examples from literature and own experience demonstrate that the importance of the 'Fecal Indicators' for the judgement of 'hygienic conditions' in food production are rather limited and a correct evaluation only by 'Bacterial Plate Counts' is not possible due to the variation of germ density within one sample. Microbiological investigations of food products according to statistic rules require such an expenditure that they cannot generally be used as routine control procedures. A possible documentation is shown which allows - even without statistic investigations, at least retrospectively - the preparation of a survey on the microbiological properties of raw materials generally available on the market and which makes it possible to recognize and reject any unqualified microbiological limiting value requirements. PMID- 6252724 TI - [Rendering of animal material in the Netherlands (author's transl)]. AB - Just before the World War II rendering of all material of animal origin unfit for human and animal consumption was a fact and was later on regulated by Decree in 1942. The rendering act dates from 1957 referring to as "processing into useful product". There is a compulsery rendering which means that withdrawal of the material mentioned from rendering is in general prohibited. Material for rendering must be notified. In use is the dry rendering system (atmospheric batch cookers). At the moment there are four (three large and one small) rendering plants, the first being established in 1926, and they are under strict government supervision but not under government management. A licence is needed. Supervision is carried out by the Veterinary Public Health Inspectorate. After heating no micro-organism must be present and therefore regular checks for Clostridium perfringens as an indicator organism are carried out besides a contol of ther thermocharts. Recontamination should be avoided. As a result of the extensive bacteriological control since 1972 (Salmonella and other enterobacteriaceae, the latter as indicator organisms) there has been noticed a still growing improvement of the hygienic condition in the rendering plants. During the past half year Salmonella could not be isolated from samples endproduct. Transportation of raw material for rendering after notification to the head of the municipal meat inspection service is done by the rendering plant in completely watertight vehicles. There is a Rendering Board which must be consulted when legislative measures related to rendering are taken. PMID- 6252725 TI - [Computation for the sterilisation process in rendering plants (author's transl)]. AB - In the present paper a mathematical model for the computation and costing of the sterilisation process in rendering plants has been developed and the computation of the F value in the canning industry has been used as a guide. In this, a test germ with the heat resistance parameters z = 10 degrees C and Dr = 10 sec is taken as a guide. If the steam-pressure heating regulation of the German Carcass Disposal Act which prescribes a temperature of 133 degrees C during 20 min after decomposition of the soft parts, is related to such a test germ, then a comparable sterilisation time of roughly 300 min at 121 degrees C is obtained, the heating-up phase and the cooling-down phase being disregarded. In computing the total lethality of a practical heating procedure in a dry melter, the result is a comparable heating process of abt. 640 min at 121 degrees C. While making allowance for the time lags in the temperature development in meat and bones during autoclaving and on the basis of a heating-up value of 100 minutes at 121 degrees C, various steam-pressure heat treating systems are suggested within the temperature range from 120 to 135 degrees C, having a comparable total lethal effect varying in duration. PMID- 6252726 TI - Effects of training on adreno-cortical function and red-cell volume in trotters. PMID- 6252728 TI - Detection by immunodiffusion- and radioimmunoassay-tests of antibodies to bovine leukemia virus antigens in sera of experimentally infected sheep and cattle. PMID- 6252727 TI - [Seroepizootiology of canine herpes virus infections in Switzerland and preliminary studies with a vaccine]. PMID- 6252729 TI - Probable horizontal spread of bovine leucosis virus not followed by secondary disease outbreaks. PMID- 6252730 TI - A pilot study of the potency of a combined Newcastle disease (fowl pox) fowl typhoid vaccine. I. The Newcastle disease component. PMID- 6252731 TI - [Effect of adrenocorticotropin fragments on the memory of Tenebrio molitor beetles]. AB - Fragments of the adrenocorticotropic hormone ACTH1-24 and ACTH5-7 facilitate memory in the beetle T. molitor, the effect being observed at different stages after learning. An analogue of ACTH5-7 which contains D-phenylalamine, as well as D-phen7-ACTH4-7, inhibit memorization (the results checked 1 day after learning) and induce some other disturbances in the behaviour of beetles. To the 10th day of learning, the effects of the analogues cannot be distinguished from those of L Phe7-fragments. The results obtained are compared with the known effect of ACTH fragments on memory in vertebrates. PMID- 6252732 TI - [Effect of calcium deficiency and addition of calcium antagonists on motoneuron synaptic potentials of isolated Emys orbicularis turtle spinal cord]. AB - In experiments carried out on the isolated spinal cord of the tortoise Emys orbicularis postsynaptic potentials produced in spinal motoneurons by stimulation of the descending tracts and dorsal roots were investigated by means of the intracellular recording technique. Postsynaptic potentials were completely and reversibly blocked in Ca2+-free solutions containing 5.0 mM Mg2+ or 2.0 mM Mn2+. The amplitude and frequency of spontaneous synaptic potentials were also reduced under these conditions. The effect of Ca2+-free medium indicates that the synaptic transmission in these synapses is mediated by chemical mechanism. PMID- 6252733 TI - [Effect of morphine, beta-endorphin, and met-enkephalin on electrical activity of Helix pomatia snail neurons]. AB - Application of morphine and methionine-enkephaline using microionophoretic technique (20-100 nA, 1-15 sec) or perfusion (10(-7)--10(-6) M) caused inhibition of the impulsation, which in some of the cases was accompanied by hyperpolarization of the membrane and the decrease in its resistance, as well as by the reduction of EPSP's. The increase in impulsation with membrane depolarization was less frequent. beta-Endorphine (10(-7)--10(-6) M) caused a substantially longer inhibition of the impulse activity than morphine or met enkephaline. PMID- 6252734 TI - [Features of vertebrate brain Na,K-adenosine triphosphatase activation by detergents]. AB - Studies have been made on changes in the activity of Na,K-ATPase in brain homogenates of vertebrates (rat, hen, frog, tortoises) induced by various detergents (sodium deoxycholate, Twin-20, Twin-80, Triton X-100). After application of detergent at optimal concentrations, usually the enzymic activity increased, the increase being dependent on animal species and the brain structure. In crude homogenate of the forebrain, Na,K-ATPase activity was the highest in hen and was altogether absent in frog; detergents practically did not affect the enzymic activity in hen and sharply increased it in frogs. It is suggested that the activating effect of detergents is associated with damage of vesicular membrane structures which are formed during homogenization of the brain tissue, the degree of vesicularization being dependent on fatty acid composition of membrane phospholipids of the brain. PMID- 6252735 TI - [Certain functional connections of neurons control the walking of the cockroach Periplaneta americana]. AB - On isolated abdominal nervous chain of the cockroach studies have been made of the responses of motoneurones of the thoracic ganglion to electrical stimulation of afferent axons of the leg nerve under normal conditions and during application of an anticholinesterase drug, GD-7. Depending on the type of stimulated axons, monosynaptic response, as well as polysynaptic phasic and tonic responses of motoneurones were recorded. A scheme of activation of motoneurones is suggested which evokes slow contractions of muscles in cockroach extremities. PMID- 6252736 TI - [Cyclic nucleotide phosphodiesterase in the taste buds of the catfish Ictalurus nebulosus]. PMID- 6252737 TI - Differential alpha- and beta-adrenergic responsiveness of beating rat heart myocytes after stationary and non-stationary cultivation. AB - Spontaneously beating myocytes from the heart ventricles of 1 to 4-day old rats were maintained for 8 days in stationary or in rocker culture under otherwise identical conditions and exposed to phenylephrine and isoproterenol for comparison of their positive chronotropic responses to alpha and to beta adrenoceptor stimulation, respectively. The heart myocytes in rocked culture were more sensitive to phenylephrine and less sensitive to isoproterenol than were the myocytes in stationary culture and they also displayed a greater maximal response to the alpha-agonist. Addition of 1 mM L(+)-lactate to the rocker cultures abolished alpha-adrenergic responsiveness in one third of the cases while persistently increasing beta-adrenergic sensitivity. PMID- 6252738 TI - Conformational changes of hemoproteins as evidenced by second derivative spectroscopy of aromatic amino acids. AB - Based on a comparison of the 2nd derivative spectra of cytochrome P-450 LM2, cytochrome c and hemoglobin with the corresponding mixtures of aromatic amino acids and the individual aromatic amino acids a significant red shift of the maxima of the absorption bands appearing as distinct minima in the 2nd derivative spectrum have been observed in the proteins. This red shift has been shown to be caused by a lowered polarity of the immediate surroundings of the chromophores. The band positions of the aromatic amino acids in the 3 investigated hemoproteins are nearly the same and therefore do not allow to qantitate conformation dependent spectral changes of the chromophores. In agreement with X-ray crystallographic data aromatic amino acids of cytochrome c and of hemoglobin are subjected to spectral changes at the transition from the oxidized to the reduced state. These redox linked conformational changes are indicated by significant changes of the amplitudes of the aromatic acids in the 2nd derivative spectrum. A quantitative evaluation of the amplitudes revealed characteristics specific for cytochrome c and hemoglobin. Surprisingly the 2nd derivative spectrum in the median UV-region of cytochrome P-450 LM2 does not show any significant change at reduction. PMID- 6252739 TI - [Calculation of the g-factors of hemoproteins with the crystal field theory. Development of a 3-term model]. AB - A 3-term crystal field model is used for the calculation of the magnetic properties of ferric hemoproteins. This model includes the high spin term (6A1), the low spin term (2T2) and the quartet term (4T1). The pertubation matrix between these 3 terms caused by spin orbit coupling and ligand fields of cubic, axial and rhombic symmetry are evaluated. The g-factor of the low spin cytochrome P-450 LM2 from rabbit liver are calculated using this 3-term model and the results are compared with those from the usual 1-term model. Contrary to the 1 term model, no orbital moment correction factor is necessary. That means that the orbital moment correction factor with value > 1 simulates some term interaction, predominantly with the quartet term. The g-factors of the high spin cytochrome P 450 LM4 were also calculated by means of the 3-term model and compared with a spin hamilton treatment. A good agreement between the spin hamilton parameters derived from the experimental g-factors and those calculated by the 3-term model were obtained. For hemoproteins with strongly mixed spin states the 3-term model is also useful, contrary to 1-term models or spin hamiltonians which are completely incorrect. The 3-term model is a minimal model to describe all typical magnetic properties of low spin and high spin ferric hemoproteins with the smallest number of terms. PMID- 6252740 TI - [The interaction of methemoglobin and modified poly-(hydroxyethylmethacrylates) studied by spectroscopic methods]. AB - The interaction between methemoglobin (MetHb) and macroporous matrices on the basis of polymethacrylates was investigated by means of optical and e.p.r. spectroscopy. The spectroscopic data show that the adsorption of MetHb to imidazole-containing matrices occurs by complex formation between matrix-bound imidazole and the iron of the prosthetic group, with all 4 polypeptide chains of the MetHb molecule being included in the interaction. The adsorption to hydrophobic side chains containing matrices leads, via the protein-matrix interaction, to considerable disturbances of iron protoporphyrin IX in equilibrium or formed from protein-contacts, which are of general importance with respect to the functional variablity and control, respectively, of iron porphyrins in hemoproteins. In case of matrix containing n-hexyl groups deoxyHb is oxidized by O2 to MetHb, instead of being oxygenated to HbO2. Not all prosthetic groups are able to bind N-3. With the increase in hydrophobicity of the matrix a conformational change is enforced leading in the beta-chains to the direct interaction between iron and sulfur of cysteine (beta-cys 92), as it is proved in all cytochrome P-450 and other model compounds. PMID- 6252741 TI - Effect of magnesium-dependent cell membrane alterations on the transport of K+ in Ehrlich ascites tumour cells. AB - Mg-deficiency or Mg-loading of tumour cells changes the permeability of the cell membrane. The influence of this change on the K+ transport across the membrane was investigated using 86Rb+ and K+ analog. The time course of the influx and efflux rates were estimated by means of a mathematical approach for a two compartment system with inconstant pool sizes. The comparison of the two states of the cells demonstrates that in Mg-deficient cells the passive K+ efflux is significantly enhanced (40%). This in turn stimulates the active counter transport mediated by the (Na+-K+)-ATPase, raising the ATP consumption by about 30%. However, the enzyme is not able to maintain the cellular K+ content under these conditions. After a short transient increase due to the initially enhanced influx the passive net efflux prevails. Differences in the electrophoretic mobility of the two states of the cells confirm Mg-dependent changes of the cell membrane structure. PMID- 6252742 TI - [Participation of a phosphatase in the Ca regulation in actomyosin preparations from smooth vascular muscle]. AB - The superprecipitation of actomyosin from the A. carotis of cattle is suppressed by a phosphatase containing protein fraction. This inhibition is compensated by ammonium molybdate, an inhibitor of phosphatase activity. The results are related to a phosphorylation-dephosphorylation cycle to realize the Ca-sensitivity of superprecipitation of the actomyosin. PMID- 6252743 TI - Pituitary Cushing's disease without adenoma. AB - Recent reports of patients with Cushing's disease who have been explored via the transsphenoidal route indicate that the great majority has pituitary adenomas. We report a patient with biochemically documented pituitary-based hypercortisolism who had a clinical and biochemical remission following hypophysectomy. Serial sections of the pituitary tissue removed showed hyperplasia of corticotroph cells but no adenoma. Hypophysectomy was complete as documented by serum levels of FSH, LH, TSH, prolactin, hGH and ACTH at the lower limits of the respective assays, with no response to appropriate stimuli. This case demonstrates that a minority of patients with Cushing's disease has corticotroph cell hyperplasia without a pituitary adenoma. PMID- 6252744 TI - Inhibition of vasopressin secretion by a met-enkephalin (FK 33-824) in humans. AB - To investigate the effect of a met-enkephalin analogue, FK 33-824, on renal handling of water, 8 subjects were given 0.5 mg im of the drug or placebo in a cross-over study. In a second trial under the same testing conditions, a 4 mg dose of naloxone iv was given to 6 subjects immediately preceding 0.5 mg FK 33 824 im. Urine and blood samples were collected at hourly intervals. Urinary vasopressin (AVP) and plasma prolactin (Prl) were assayed, and free water clearance (FWC) was calculated. Following the same protocol, a further 6 subjects received 5 IU of lysine vasopressin im 5 min preceding administration of FK 33 824. FK 33-824 significantly (P < 0.001) increased Prl and FWC and reduced urinary concentrations of AVP (P < 0.01). Naloxone pre-treatment failed to modify significantly the latter two responses, while Prl stimulation was inhibited. Lysine vasopressin pre-treatment abolished the effect of FK 33-824 on FWC while the stimulating action on Prl was preserved. These results indicate that in humans FK 33-824 reduces AVP secretion and that this effect is not mediated by naloxone sensitive opiate receptors. PMID- 6252745 TI - Relationship between insulin secretion, insulin content and dry weight of single rat pancreatic islets. AB - Single islets were incubated at glucose 5 mM for 60 min and subsequently at glucose 15 nM for 30 min. The insulin content of the incubated islets was proportional to the dry weight of the islets. The insulin secretion (Y) demonstrated a curvilinear relationship with the dry weight (X) of the islets, which could be described by the function Y = aX2/3 (a being a constant). On basis of this function it can be calculated that the insulin secretion of a particular islet is proportional to its outer surface. The consequence of this is that small sized islets secrete relatively much more insulin than large islets. Islets isolated with either purified or crude collagenase gave the same results except that a higher basal insulin secretion was observed with crude collagenase. PMID- 6252746 TI - Hepatitis markers detected in a Canadian blood donor population. PMID- 6252747 TI - ATP, beta-gamma-methylene-ATP, and adenosine inhibit non-cholinergic non adrenergic transmission in rat urinary bladder. AB - ATP and adenosine caused a dose-dependent and reversible inhibition of the atropine-resistant contraction response to transmural nerve stimulation in the rat urinary bladder. Both purines also inhibited contraction responses to acetylcholine and direct muscle stimulation, indicating a postjunctional effect on the transmission. It seems as ATP per se inhibits the excitatory transmission, because the stable ATP-analogue beta-gamma-methylene-ATP was inhibitory as well, and because exogenous adenosine deaminase annulled the inhibition by adenosine but not that by ATP or beta-gamma-methylene-ATP. Blockade of purine inactivation enhanced the inhibitory action of ATP and adenosine, and by itself inhibited the transmission. These results are consistent with the possibility that endogenous purines may modulate non-cholinergic non-adrenergic excitatory transmission in the rat urinary bladder. PMID- 6252748 TI - Effect of physical training on skeletal muscle metabolism and ultrastructure in 70 to 75-year-old men. AB - The effects of a 12-week program of physical training on skeletal muscle (vastus lateralis) characteristics in 5 old men were investigated. Heart rates during submaximal bicycle exercise were decreased after training, indicating an improved cardiovascular function. As judged from enzyme activity measurements, the anaerobic capacity as well as the mitochondrial oxidative capacity were increased by the training. Fatty acid oxidation capacity remained unchanged, while the glycolytic potential tended to be increased, suggesting a somwehat different pattern of adaptation as compared to that seen in young subjects. Volume fractions of mitochondria and lipid droplets were unchanged with training, supporting the view that in old men, increases in oxidative capacity take place within the existing mitochondrial volume. It was concluded, that the aging human skeletal muscle remains trainable, and that the training response is similar, but possibly not identical, to that seen in younger age groups. PMID- 6252749 TI - Selective vein catheterization for hormone assay in endocrine tumours of the pancreas. Technique and results. AB - Based on 45 examinations the technique of selective catheterization of the pancreatic veins for blood sampling using percutaneous transhepatic approach to the portal vein is described. The results are compared with the angiographic findings in 16 patients with islet cell tumours of islet cell hyperplasia. PMID- 6252750 TI - Qualitative and quantitative effects of ACTH, piromen, cytoxan and isobutyl-2 cyanoacrylate treatments following spinal cord transection in rats. AB - Adult, male, Long-Evans hooded rats were subjected to a spinal cord transection in the mid-thoracic region. Following surgery, animals were divided into groups for treatments with ACTH, Piromen, isobutyl-2-cyanoacrylate and Cytoxan. Animals were sacrificed at varying intervals from 7-180 days. Horizontal sections of the lesion site were stained with the Bodian silver and Gomori trichrome techniques and numbers of nerve fibers counted within the lesion. Statistical analysis of the quantitative data indicated that Piromen and Cytoxan, respectively, were significantly more effective than the other treatments in promoting regeneration of nerve fibers into the scar. Microcysts appeared adjacent to the lesion in all animals early in the postoperative period and coalesced to form large cavitations which continued to enlarge throughout the postoperative period. Although nerve fibers appeared to traverse the lesion, no return of function was observed. PMID- 6252751 TI - The response patterns of collicular neurons to moving stimuli in cats after lesion of the visual cortex. AB - The speed and direction selectivity of responses of collicular neurons in pretrigeminal cats following lesions of the visual cortex were examined using moving light spots. Following cortical lesions the number of cells showing direction selectivity was reduced, but the number of cells showing speed selectivity was increased. It is suggested that some of the characteristics of collicular neurons are dependent on initial organization of the intracollicular synaptic connections rather than the corticocollicular ones. PMID- 6252752 TI - The influence of chloralose anesthesia on the activity of red nucleus neurons in cats. AB - In unanesthetized cats peripheral stimulation typically evoked the short-latency excitation followed by short "inhibition". After administration of chloralose a gradual formation of long-lasting excitatory-inhibitory-excitatory response was observed. PMID- 6252754 TI - Brain tumour associated with intracranial arterial aneurysm. AB - Four cases of brain tumour associated with intracranial aneurysm are presented, and the available literature is reviewed. The association of brain tumours and arterial aneurysms is not well documented in neurosurgical literature. Reports of the association of giant aneurysms with brain tumours are rare. We could find only five such cases, and one of our cases is the sixth. The operative mortality of the patient with coexisting brain tumour and cerebral aneurysm is high. Two of our cases died postoperatively, one from pre-existing cardiac disease, and the other from hypothalamic vascular insuffiency related to surgery. PMID- 6252753 TI - Functionless non-chromaffin retroperitoneal paraganglioma causing cauda equina compression. AB - The authors describe a case of functionless non-chromaffin paraganglioma of the retroperitoneal space, that invaded the spinal canal causing a cross section syndrome of the cauda equina. The case is described because of the unusual clinical evolution of the tumour in question, never previously described. PMID- 6252756 TI - Clinical variability of the gouty diathesis. PMID- 6252755 TI - Serum 5-nucleotidase in progressive muscular dystrophy. PMID- 6252757 TI - AMP phosphatase activity in human term placenta: studies on placental 5' nucleotidase. PMID- 6252758 TI - The phosphaturic action of PTH in the steady state in patients with normal and impaired renal function. PMID- 6252759 TI - The control of phosphate uptake by the isolated renal tubule. AB - An in vitro isolated tubular model is presented which appears to have many characteristics of an active transport system in that Pi accumulation by the preparation is sodium- and temperature-dependent, stimulated by PTH and cAMP and is also conditioned by the metabolic integrity of the tissue. The relationship between the observations made in the dispersed convolutal tubule preparation in the present study and the mechanisms by which PTH affects phosphate transport in isolated perfused tubules and in vivo has not yet been ascertained. PMID- 6252760 TI - Altered vitamin D, cyclic nucleotide and trace mineral metabolism in the X-linked hypophosphatemic mouse. AB - Hyp mice have a defective control system for the synthesis of 1,25-(OH)2-vitamin D that does not respond to a low phosphate stimulus. While the plasma levels of 25-OH-vitamin D are reduced somewhat, this seems to be not a serious defect since plasma 1,25-(OH)2-vitamin D levels are normal. Hyp kidneys synthesize and excrete elevated levels of cyclic AMP and cyclic GMP. The elevated tissue levels of trace minerals suggests increased food intake with normal intestinal absorption of the minerals. In addition there is the reduced renal tubular reabsorption of phosphate caused by a change in the brush border transport of phosphate. This leads to hypophosphatemia, osteomalacic bone disease and altered Mg metabolism. There is intestinal resistance to 1,25-(OH)2-vitamin D stimulation. Many of these defects seem unrelated to the reduced renal tubular reabsorption of phosphate. Yet all are derived from one mutation in the Hyp gene. The underlying explanation must account for all abnormalities by a single mutation in a single gene product. The near normal phosphate levels in soft tissues and the multiple defects argue against a genetic change in the phosphate pump as an ultimate explanation. Still to be explored are possible changes in a phosphate recognition site on a cell membrane or a change in an as yet unknown phosphate regulating system. PMID- 6252761 TI - Urolithiasis research: progress and trends. PMID- 6252762 TI - The parathyroid hormone receptor-adenylate cyclase system in chicken kidney. PMID- 6252763 TI - Renal receptors for parathyroid hormone in normal, parathyroidectomized and vitamin D-deficient rats. PMID- 6252764 TI - Antagonistic effects of 25(OH)vitamin D3 and peptide hormones on the activation of adenylate cyclase/cyclic AMP system in renal tissue in vitro. PMID- 6252765 TI - Multivariate analysis of the vitamin D endocrine system: evidence for the essentiality of both 24R,25-dihydroxyvitamin D3 and 1 alpha, 25-dihydroxyvitamin D3. PMID- 6252766 TI - Structure of cytochrome c oxidase. PMID- 6252767 TI - The ATP synthesizing system of liver mitochondria. PMID- 6252768 TI - Effects of chronic ethanol consumption on the respiratory chain of rat liver submitochondrial particles. AB - Studies of hepatic submitochondrial particles, which provide an experimental system allowing direct measurements of electron transfer independent of substrate transport reactions, showed that chronic ethanol ingestion (36% calories, 40 days) lowered the specific respiratory rates associated with substrate oxidation. NADH oxidase activity was decreased about 40%, succinoxidase was decreased 25%, and oxidation in ascorbate mediated by phenazine methosulfate was decreased 20%. The content of dithionite-reducible cytochrome aa3 was decreased 38%, while that of cytochrome b was decreased 8%, and that of cytochromes c + c1 was decreased 14%. Steady state kinetic measurements indicated that the turnover number of cytochrome oxidase was unchanged, about 15 s-1 under uncoupled conditions with NADH as substrate. When electron flux to cytochrome c was maximal, cytochrome c was maintained in a more highly reduced state relative to cytochrome aa3 in submitochondrial particles from the ethanol-treated rat compared to those from the control rat. This finding is consistent with the greater decrease in cytochrome aa3 content relative to that of cytochrome c. The results indicate that the diminished content of cytochrome oxidase is one of the factors responsible for the lower respiration rates caused by chronic ethanol consumption. PMID- 6252769 TI - Changes in liver inorganic pyrophosphate content during ethanol metabolism. AB - The injection of ethanol (70 mmol/kg body weight) into male Wistar rats fed ad libitum caused an increase within 15 min in the liver inorganic pyrophosphate (PPi) content from 0.012 +/- 0.001 mumol/g (wet weight) to 0.029 +/- 0.001 mumol/g. The injection of acetate (20 mmol/kg body weight) increased the liver PPi to 0.157 +/- 0.075 mumol/g in 15 min. The alcohol dehydrogenase inhibitor 4 methylpyrazole blocked the accumulation of acetate and the increase in PPi was prevented. Disulfiram, an inhibitor of aldehyde dehydrogenase, did not prevent changes in redox state, but the accumulation of acetate in the liver was decreased and the increase in liver PPi content was diminished (0.019 +/- 0.003 mumol/g). These data suggest that the increase in PPi observed after injection of ethanol may be due to the activation of the acetate produced during ethanol and acetaldehyde oxidation. PMID- 6252770 TI - A comparison of behavioral and neurochemical effects of ethanol and chlordiazepoxide. AB - Many similarities were observed in the behavioral and neurochemical actions of ethanol and chlordiazepoxide (CDZ) suggesting that these agents may share common mechanisms of action. However, similarities in these actions could not be explained by effects on a benzodiazepine binding site, since only CDZ interacted with this locus. PMID- 6252771 TI - Receptor and membrane function in the alcohol tolerant/dependent animal. AB - Neurochemical changes which are associated with the development or expression of tolerance to or physical dependence on ethanol may be expected to display a time course of appearance and disappearance which correlates positively with the time course for tolerance or dependence. Previous studies of striatal dopaminergic receptor function indicated that ethanol-withdrawn mice displayed decreased physiological and biochemical responses to dopamine (DA) agonists, which could be best explained by postulating an inefficient coupling between DA receptors and various receptor-mediated processes, possibly as a result of ethanol-induced changes in neuronal membrane properties. The membrane-bound enzyme, (Na+ K+)ATPase, obtained from ethanol-withdrawn animals, displays an altered transition temperature and resistance to the effects of ethanol on enzyme activity. These changes also suggest compensatory alterations in neuronal membrane properties. All of these alterations show a time course of disappearance which corresponds to that for the disappearance of tolerance to the hypothermic and sedative effects of ethanol. Ethanol-withdrawn mice also display increased numbers of hippocampal muscarinic cholinergic receptors; however, the time course for the increase in receptor number appears to correlate with that of withdrawal symptomatology. Thus, compensatory changes in neuronal membrane properties in response to ethanol may be expressed via diverse functional changes. PMID- 6252772 TI - Adenovirus type 10 keratoconjunctivitis with increased intraocular pressure. AB - An 18-year-old man, with serologically diagnosed adenovirus type 10 infection, had keratoconjunctivouveitis of both eyes after pharyngitis with transient increased intraocular pressure. Increased intraocular pressure, ranging from 46 to 28 mm Hg during medical therapy, lasted for about ten days in the early stage of the disease. Many punctate corneal opacities developed bilaterally two weeks later and disappeared within ten months. Analysis of the clinical findings demonstrated that the increased intraocular pressure may have been secondary glaucoma due to keratoconjunctivitis caused by adenovirus infection. PMID- 6252773 TI - Clinical anophthalmia associated with congenital cytomegalovirus infection. AB - Three cases of congenital clinical anophthalmia associated with congenital cytomegalovirus infection were diagnosed by positive viral cultures and immunologic studies. Ultrasonography in one infant with clinically detected anophthalmia showed the presence of severe microphthalmia with cyst. These findings suggest that maternal infection occurred within the first trimester of gestation. PMID- 6252775 TI - Image alterations in the teaching microscope. A source of error in synovial fluid crystal identification. AB - An erroneous identification of sodium urate and calcium pyrophosphate crystals in synovial fluid may occur when utilizing compensated polarized microscopy with a dual-viewing-head teaching microscope. This is due to alteration of the observed image orientation with respect to the actual orientation of the crystal in space. By viewing a simple geometric figure through each microscope head, two basic types of image alterations are identified: a 180-degree rotation and a mirror image transformation. Combinations of these two may also occur. This problem is clarified and illustrated and suggestions are offered to avoid erroneous crystal identification. PMID- 6252774 TI - Dietary fibers. III. Effects of chronic intake on cholesterol absorption and metabolism in the rat. PMID- 6252776 TI - Primary hepatocelluar carcinoma in Saudi Arabia. A clinicopathological study of 54 cases. AB - A high incidence of primary hepatocelluar carcinoma in the Orient and Africa has been reported. It is also seen frequently in Saudi Arabia. In a series of 54 consecutive patients diagnosed histologically, the male to female ratio was 10:1- the highest reported. The peak age was between 40-60 years and the mean survival was eight months. This is in contrast to hepatocelluar carcinoma in Africa where the age is between 25-35 years and the disease runs a quick downhill course simulating an abscess. Macronodular cirrhosis was diagnosed histologically or suggested clinically in 80% of the cases. Serum was positive for HBsAg in 55% of the patients, compared with 8% in healthy blood donors. These figures are as significant as reports from high incidence areas and point strongly to a possible causal relationship between HBV infection and the development of primary hepatocellular carcinoma. PMID- 6252778 TI - Testimony of the American Society for Medical Technology before the Center for Disease Control's Public Hearing on proposed personnel standards. PMID- 6252777 TI - Serologic evidence for parainfluenzavirus infection during isolation at South Pole Station, Antarctica. AB - Two distinct mid-winter outbreaks of respiratory tract illness (RTI) occurred among South Pole Station personnel during the winterover period of 1976. One outbreak began early in May eight weeks after total isolation began, the second occurred in August and September after 20 weeks of complete social isolation. Sequential sera collected from 16 of the 18 subjects wintering at South Pole during 1976 were tested by hemagglutination inhibition for antibody against parainfluenzavirus types 1 and 3. Serologic responses were detected against parainfluenzavirus 1 and 3 antigens during the outbreak that occurred in May, and one subject showed a response to parainfluenzavirus 1 in September. Serologic responses occurred in both symptomatic and asymptomatic subjects and were chronologically compatible with the observed illnesses. Throat swabs collected both routinely during the winter and during each outbreak of illness and maintained at -70 C failed to reveal the causative agent when inoculated into cell culture at the home laboratory the following year. Outbreaks of mid-winter RTI and serologic responses in adult subjects isolated at South Pole Station suggest persistence of parainfluenzavirus in the human adult. Confirmation of this observation will require recovery of the virus during outbreaks of RTI within this isolated community. PMID- 6252779 TI - The effect of dihydroxy bile acids on intestinal secretion, cyclic nucleotides, and Na+-K+-ATPase. AB - The effects of dihydroxy bile acids on intestinal cyclic nucleotides, Na+-K+ ATPase, and net secretion, and of propranolol pretreatment on these actions were determined. Ileal and colonic loops were constructed in each of 12 rabbits, six of which were treated with propranolol preoperatively. In random order, normal saline, 6mM deoxycholic, chenodeoxycholic, or ursodeoxycholic acids were injected into the intestinal loops. Five hours after, net luminal secretion and mucosal adenylate cyclase, phosphodiesterase, cGMP, and Na+-K+-ATPase were determined. Deoxycholic and chenodeoxycholic acids each increased adenylate cyclase activity (< 0.01) and net secretion (p < 0.01), and decreased cGMP (p < 0.05). Ursodeoxycholic acid did not alter adenylate cyclase activity or secretion but increased cGMP (p < 0.05). Phosphodiesterase and Na+-K+-ATPase were unchanged. Propranolol reversed all of the bile acid effects. In conclusion, chenodeoxycholic and deoxycholic acid induce net intestinal secretion, probably via cAMP. Ursodeoxycholic acid does not affect cAMP but increases cGMP and does not promote net secretion. PMID- 6252780 TI - The role of adjuvant therapy in Stage I ovarian cancer. AB - Women with Stage I epithelial carcinoma of the ovary were initially treated by an extirpative operation and were subsequently randomized to either no further treatment, radiotherapy, or chemotherapy. Only two patients (6%) treated with chemotherapy developed recurrence, compared to five (17%) and seven (30%) patients in the no-treatment and radiotherapy regimens, respectively (P < 0.05). All patients, with the possible exception of those with Stage IA(1)g1, appeared to benefit from adjuvant chemotherapy compared to no treatment or radiotherapy. PMID- 6252781 TI - Isoelectric heterogenity of human chorionic gonadotropin: Presence of choriocarcinoma specific components. AB - Comparative clinical studies were carried out on the isoelectric heterogeneity of serum human chorionic gonadotropin (hCG) in normal pregnancy and trophoblastic disease by means of isoelectric focusing and radioimmunoassay. The immunoreactive hCG components in sera of women with normal pregnancy were composed of seven peaks with isoelectric points of 3.9, 4.1, 4.4, 4.7, 5.0, 5.8, and around 6.7. These same components were also observed in the sera of patients with hydatidform mole and invasive mole. However, in the sera of patients with choriocarcinoma, three additional components with isoelectric points of 3.2, 3.5, and 3.7 were observed in considerable amounts. The presence of those three specific components suggests the possibility to develop a new diagnostic procedure for the detection of choriocarcinoma. PMID- 6252782 TI - Early steps in prostaglandin metabolism in the human placenta. AB - The activities of the enzymes catalyzing in the early steps in prostaglandin metabolism (the nicotinamide adenine dinucleotide [NAD]-linked 15 hydroxyprostaglandin dehydrogenase, the nicotinamide adenine dinucleotide phosphate [NADP]-linked 15-hydroxyprostaglandin dehydrogenase, and the 15 ketoprostaglandin delta 13 reductase) were measured in homogenates of term placenta. The NAD-linked enzyme possesses the highest activity of the three. The NADP-linked enzyme has much lower activity and probably acts physiologically as a 9-ketosprostaglandin reductase rather than as a 15-hydroxyprostaglandin dehydrogenase. Placental homogenates contain a low-molecular-weight, heat-stable inhibitor of the NADP-linked enzyme. The reaction catalyzed by the 15 ketoprostaglandin delta 13 reductase is the rate-limiting step. Analysis of the activity of these enzymes has shown that there is no significant relationship between them; furthermore, whether the placentas are from spontaneous single or twin deliveries, induced deliveries, or cesarean sections (in labor or not in labor) does not have a significant effect on the activity of the NAD- or NADP linked dehydrogenases. PMID- 6252783 TI - Implant follow-up. PMID- 6252784 TI - Effect of hydrazine on transport on toad urinary bladder. AB - Vasopressin stimulates osmotic water flow and urea permeability in the toad urinary bladder via separate cAMP-responsive mechanisms. Hydrazine (10--20 MM), added to the bladder's serosal bath, reversibly enhanced the effect of both low and saturating levels of vasopressin on osmotic water flow, without increasing urea permeability. A small increase in basal water flow was also observed. Cyclic AMP-stimulated water flow was not altered by hydrazine, but hydrazine enhanced the effect of both 8-bromo-cyclic AMP and methylisobutylxantine. Hydrazine increased luminal membrane aggregate frequency in vasopressin-treated tissues examined by freeze-fracture electron microscopy. Hydrazine increased both basal and vasopressin-stimulated adenylate cyclase activity. We could measure no effect of hydrazine on cAMP content; however hydrazine did increase the protein kinase activity ratio (-cAMP/+cAMP) in vasopressin-treated tissues, suggesting that the kinase activity ratio is more sensitive than cAMP content as an index of cAMP related function in the bladder. Further strengthening the relationship between kinase activation and water flow, we found that methohexital, an inhibitor of vasopressin-stimulated water flow and adenylate cyclase, also decreased the kinase activity ratio in the presence of vasopressin. These studies link closely the role of cAMP-dependent kinase and luminal membrane aggregates to the specific mediation of vasopressin-stimulated water flow in the bladder. PMID- 6252785 TI - Basal norepinephrine overflow into the renal vein: effect of renal nerve stimulation. PMID- 6252787 TI - Histamine and cAMP as possible mediators of acetylcholine-induced acid secretion. AB - Data are presented in support of the role of histamine and adenosine 3',5'-cyclic monophosphate (cAMP) as mediators of acetylcholine-induced acid secretion in frog gastric mucosa. These data also support the notion that acetylcholine-induced alkaline secretion is mediated by guanosine 3',5'-cyclic monophosphate (cGMP). Tissue cAMP and cGMP and rates of acid secretion and histamine release were measured in in vitro preparations of frog gastric mucosa that had been stimulated by acetylcholine. A transient increase in each variable was observed, the sequence of transient maxima being histamine release, cGMP, cAMP, and acid secretion. Atropine, an anticholnergic agent, eliminated all four transient increases, the variables remaining at resting levels. Metiamide, a H2-antagonist, modified the changes observed after acetylcholine stimulation. The acid secretion transience was abolished and the transient increase in tissue cAMP was greatly diminished, whereas the tissue of cGMP transience and histamine release transience remained unchanged. A model is proposed in which acetylcholine initiates two different processes, acid and alkaline secretions. PMID- 6252786 TI - Mechanism of increased potassium secretion in potassium loading and sodium deprivation. AB - Chronic K loading and Na deficiency increase the capacity of colonic cells to secrete K and are characterized by increases in Na-K-ATPase activity and, as recently shown by our laboratory, the area of basolateral membrane. The present experiments were performed in rat colon to evaluate the quantitative and qualitative changes that occur in the enzymes after induction of K adaptation. Changes in specific binding of [3H]ouabain to a plasma membrane-rich fraction of colonic mucosal cells correlated directly with changes in enzyme activity. In Na deficient animals the number of ouabain-binding sites increased from 63.6 in controls to 111.2 pmol/mg protein, while the KD for ouabain was unchanged. The Km for ATP was not altered in experimental animals, although Vmax rose twofold. Further studies showed no change in the activity of adenylate cyclase, a marker enzyme for basolateral membrane, in the plasma membrane-rich fraction from experimental cells, although Na-K-ATPase activity increased significantly. These data indicate that increased Na-K-ATPase activity in K-adapted colonic cells reflects an absolute increase in number of pump sites, due, at least in part, to an increase in area of basolateral cell membrane. In addition, in sodium-deprived animals the present data suggest an increase in the density of K pumps in basolateral cell membrane. PMID- 6252788 TI - Subcellular distribution of PRibPP synthetase activity of rat intestinal mucosa. AB - 5-Phosphoribosyl 1-pyrophosphate synthetase (PRibPP synthetase EC 2.7.6.1) isolated from rat intestinal mucosa was found to be membrane associated. The subcellular distribution of PRibPP synthetase activity seems to parallel that of gamma-glutamyl transpeptidase, indicating it to be in the brush border. The tip cells of rat intestinal mucosa were richer in PRibPP synthetase than the crypt cells. Chromatography of a Triton-solubilized particulate fraction unmasked a peak of hypoxanthine phosphoribosyltransferase activity that was not detectable before. The activity, too, was concentrated in the brush border. The coexistence of these two activities in the fraction of the bowl involved in absorption has led to the suggestin that the synthetase and phosphoribosyl-transferase are part of a coupled transport system. PMID- 6252789 TI - Effects of estradiol on release and disposition of norepinephrine from nerve endings. AB - Studies were performed to determine whether estradiol (E2) has a direct action on the release and disposition of norepinephrine (NE) from adrenergic nerve endings in isolated superfused canine saphenous veins. [3H]NE and is labeled metabolites were separated by column chromatography with measurement by liquid scintillation spectrometry. An increase in the spontaneous overflow of total 3H, [3H]NE, and [3H]dihydroxyphenylglycol ([3H]DOPEG) that occurred with 1 and 10 microgram/ml E2 in the superfusing medium suggested that E2 either induced NE release or interfered with intraneuronal NE storage. During electrical stimulation (ES), release of [3H]NE and [3H]DOPEG exceeded controls with 1 and 10 microgram/ml E2 in the superfusate, yet total 3H was little changed. The evoked release of [3H]DOPEG showed less of an elevation over its spontaneous efflux in E2-treated veins than in nontreated veins, suggesting that E2 may block neuronal reuptake of released NE. The efflux of O-methylated deaminated metabolites during and after ES was decreased by E2 treatment, suggesting also an inhibition of extraneuronal uptake of NE. PMID- 6252790 TI - Spindle-cell carcinoid tumors of the lung: a clinicopathologic study of 35 cases. AB - Thirty-five cases of spindle-cell carcinoid tumors of the lung were studied. Fifteen patients were male and 20 female, and they ranged in age from 33 to 78 years, with a mean of 57.6 years. Eleven neoplasms were located in the left lung and 23 in the right lung; a disproportionately large number of neoplasms were present in the right middle lobe. The tumors were most commonly encountered as an incidental finding on chest roentgenogram. None of the patients had unequivocal evidence of the carcinoid or any other endocrine syndrome. All but two of the lesions were located n the periphery of the lung and most were subpleural. They ranged in size from 0.7 to 4 cm, with 82% of the neoplasms having a maximum dimension of 2 cm or less. Microscopically, the neoplasms were composed predominantly or entirely of spindle cells which were fairly uniform in length in any single lesion, but showed moderate variation from case to case. The shorter spindle cells were often arranged in an "organoid" pattern, while the neoplasms composed of larger spindle cells were more "mesenchymal" in appearance. Silver stains were performed on 12 cases and all were argyrophil-positive. Cytoplasmic dense-core granules were identified in all four neoplasms examined ultrastructurally. Twelve cases were treated by wedge resection or segmental resection, and 18 cases by lobectomy. Hilar lymph nodes were removed from seven patients, and in two there were microscopic lymph node metastases. One other patient had a single microscopic bony metastasis. Follow-up information was available for 22 patients and ranged from 1 to 13 years with a mean of 5.4 years. None of the patients have had metastases other than those described above and none of the patients had died of their disease. PMID- 6252791 TI - Sclerosing hemangioma of the lung: a clinicopathologic study of 51 cases. AB - The clinical and pathologic features of 51 sclerosing hemangiomas of the lung are reviewed. This tumor is benign and occurs predominantly in women. It has a variegated histologic appearance characterized by an admixture of four major histologic patterns: solid, hemorrhagic, papillary, and sclerotic. Characteristic uniform round cells are found within the stroma in all patterns and are unique to this tumor. Sclerosing hemangioma is a distinct clinicopathologic entity and should be distinguished from other benign neoplasms or inflammatory lesions of the lung. PMID- 6252792 TI - Mullerian adenosarcoma of the uterus. PMID- 6252793 TI - Carcinoma in a rectovaginal fistula in a patient with Crohn's disease. AB - A patient with Crohn's disease underwent resection for internal fistulas. Later a rectovaginal fistula developed that persisted with minimal symptoms for 10 years before causing pain and induration in the posterior vaginal wall, due to carcinoma developing within the fistula. PMID- 6252794 TI - Influence of morphine and naltrexone on the intraocular pressure of conscious cynomolgus monkeys (Macaca fascicularis). AB - Intraocular pressure (IOP) was measured by applanation tonometry in four trained conscious monkeys (Macaca fascicularis) which were treated with morphine (5 mg/kg), naltrexone (1 mg/kg) and a mixture of both drugs (in the same doses as given separately). Morphine lowered IOP in all animals at both 20 and 40 min after drug administration. The inter-individual scatter was 1.8--11 mm Hg. Mydriasis was noted in three monkeys. Behaviour was characteristically affected. The morphine antagonist naltrexone one and the mixture of morphine and naltrexone had no effect on IOP or pupil. Behaviour, however, differed from the normal as well as the morphine-induced behaviour. The results indicate that the morphine effect on IOP must be mediated by a specific agonistic action on the morphine receptor. PMID- 6252795 TI - Electromyographic and mechanical twitch responses following suxamethonium administration. AB - Electromyographic and mechanical evoked twitch responses at the hand were observed simultaneously following suxamethonium. The intensity of neuromuscular blockade was assessed by comparison with their control heights of the responses obtained from both the force of thumb adduction and from the compound electromyogram (EMG). Surface electrodes placed dorsally over the lateral hand provided two EMG signals, one of which was assessed in terms of its amplitude, the other as the rectified and integrated energy envelope. While the mechanical and electrical events were roughly in agreement there was better conformity between the two EMG techniques in the assessment of paralysis. PMID- 6252796 TI - Computer-assisted indirect coulometric titrations of biological redox components. PMID- 6252797 TI - A new spectrophotometric assay for 2',3'-cyclic nucleotide 3'-phosphohydrolase activity in nervous tissue. PMID- 6252798 TI - Assay of adenosine 3', 5' cyclic monophosphate by stimulation of protein kinase: a method not involving radioactivity. PMID- 6252799 TI - Determination of inorganic phosphate. A method for the determination of phosphatase activity by a continuous flow system. PMID- 6252800 TI - Effects of halothane on the cyclic 3',5'-adenosine monophosphate enzyme system in human platelets. AB - A study of the effects of halothane on the cyclic 3',5'-adenosine monophosphate (cAMP) system in human platelets was undertaken since cAMP has been implicated in the regulation of the process of platelet aggregation and this anesthetic has been reported to decrease platelet aggregation and, in other tissues, to increase adenylate cyclase activity. When exposed to halothane 0.5 to 10 vol%, adenylate cyclase activity was increased in the platelet preparation in a dose-dependent manner, reaching a maximum at 5 vol% (93% increase above basal activity). Platelet aggregation was also inhibited by halothane in a dose-dependent manner, with a maximum effect at about 5 vol% halothane (a decrease of 70%). Kinetic analysis of platelet cAMP-phosphodiesterase suggested two forms of activity, neither of which was altered by halothone. The results that the impairment of platelet aggregation observed with halothane may be brought about by the halothane-induced activation of platelet adenylate cyclase, which may result in a higher cAMP level, inhibiting platelet aggregation. PMID- 6252801 TI - Carcinoma of the breast in women 30 years of age or younger. AB - Between 1960 and 1975, 20 women aged 30 years or younger and with carcinoma of the breast were treated at the Chaim Sheba Medical Center. Eight are alive four to 12 years after the primary operative treatment, and 12 have died. The most important factor affecting the ultimate prognosis was the presence of metastasis in axillary nodes, which was found in 70 per cent of the women at surgery. On the other hand, slowly progressing circumscribed tumors of the medullary and intraductal types were more frequently found, occurring in six of the patients. This fact seems to improve the prognosis. Hence, the overall survival rate of women who are 30 years old or younger with carcinoma of the breast is comparable to that of women in other age groups with the same disease. PMID- 6252802 TI - DNA content and survival in mammary carcinoma. AB - In a retrospective study of archival fine needle aspiration biopsy material from 112 patients with primary mammary carcinoma, the DNA distribution patterns of the cancer cell populations were determined. A distinct correlation was found between the occurrence of certain types of DNA distribution histograms and the survival time of the patients. Thus, the data indicate that DNA determinations can give prognostic information, in the individual case, over and above that furnished by clinical staging and morphologic criteria. PMID- 6252804 TI - [Metastatic pulmonary emboli: clinical types and incidence (author's transl)]. AB - Pathological examinations during autopsy of 1457 cases of cancer demonstrated the presence of metastatic pulmonary emboli in 10 p. cent (148 cases). The were divided, as a function of their site and histological type of the primary neoplasm, as follows: hepatoma 33 p. cent, chorioepithelioma 25 p. cent, endocrine glands 19 p. cent, biliary tract 17.6 p. cent, hypernephroma 15.6 p. cent, sarcoma 13 p. cent, and various other tumors such as cancer of the pancreas, and breast. Two anatomical types of these emboli can be distinguished: one mixed type associated with a pulmonary cancerous lymphangitis (90 cases), and observed at a later stage in the disease. This may be latent or cause a subacute cor pulmonale. The other type is not associated with lymphangitis (58 cases), results from hematogenic cancers (hepatoma, hypernephroma, etc...), is often seen at an early stage, and causes sudden death. Histological examination enabled the consequences of any infarct developing as a result of the emboli to be demonstrated, and the origin of the emboli from neoplasmatic thromboses in the primary cancer drainage routes or from metastases in the liver to be determined. PMID- 6252803 TI - [Gamma-heavy chain disease with autoimmune abnormalities and peripheral neuropathy (author's transl)]. AB - The authors report the case of a 72 year old woman affected by gamma heavy chain disease in whom the heavy chain was detected in the serum and the urine as well. Further study of the paraprotein showed that it belonged to the gamma 1 subclass. This observation was unusual because of the presence of a 15 year-long peripheral neuropathy and the existence of various auto-antibodies, especially intrinsic factor antibody. PMID- 6252805 TI - The lactose transposon Tn951: characterization of transposition. AB - Transposition of the lactose transposon Tn951 was found to still occur in the absence of its original host plasmid pGC1. Transposition was recA-independent. These results show that Tn951 is indeed a transposon. A computer program was developed to facilitate mapping of transposon integration sites in plasmids from restriction data. PMID- 6252807 TI - Cystosarcoma phylloides presenting as massive unilateral breast hypertrophy in an adolescent. AB - A 14-year-old girl presented with unilateral massive breast enlargement while the opposite breast had minimal development. A 565 gm tumor, benign cystosarcoma phylloides, was removed by wide local excision. The literature regarding the controversial tumor is reviewed. Methods of treatment for each category of cystosarcoma phylloides, based upon morphological criteria, are outlined and the prognosis discussed. The special problem of cystosarcoma phylloides in the adolescent is reviewed and treatment recommended. PMID- 6252806 TI - [Aldosterone tests in children (author's transl)]. PMID- 6252809 TI - Liver cell cancer--a global problem. AB - Global variations in the natural history of Primary Liver Cancer and relationship to aetiology is discussed. The global incidence of this cancer is still incomplete but in Africa and the Far East where the disease is common, the establishment of Cancer Registries have provided suitable data for comparison with developed cancer registries in North America and Europe. Research into aetiology has been active in recent years and has given good clues to aetiology. Some of these studies may later lead to studies on primary prevention. PMID- 6252808 TI - The use of biochemical tests in the diagnosis of disorders of calcium metabolism. PMID- 6252810 TI - Primary hepatocellular carcinoma in the Asian Pacific region. AB - This survey was conducted to obtain current data relating to the epidemiology, aetiological factors, diagnostic tests in use, effect of various treatments and the evaluation of the extent of any population screening procedures. From replies to questionnaires sent to countries in West, South, North, South East Asian and Oceania the data showed that Primary Hepatocellular Carcinoma is common in most areas, but has a lower incidence amongst the non useful method of diagnosis. New biochemical and immunological markers are being studied. Untreated disease seldom survived more than 3 months. Various treatment protocols are being done since about 85% of tumours are non resectible at presentation. A population screening is done in China and on a risk groups in Taiwan and Singapore. PMID- 6252811 TI - Carcinoma of the liver in Thailand, trends in two decades. AB - During the past 20 years, trends have been observed in primary hepatocellular carcinoma in Thailand. There is a definite increase in the association between HCC and cirrhosis of liver from 16.6% in 1958 to 50.78% in 1968 and 73.93% in 1978 series. The increase in percentage is associated with increase in mean age group from 44.61 +/- 9.77 in 1958, to 48.84 +/- 12.35 (p < 0.01) in 1978. This reflects the important role which hepatitis B plays in the etiology of HCC associated with cirrhosis in Thailand. Also, the aggregation of people in the city of Bangkok may cause an increase in the hepatitis B carrier. PMID- 6252812 TI - An Australian experience of hepatitis B infection, cirrhosis and hepatocellular carcinoma. AB - A review of 180 patients with either chronic hepatitis or hepatocellular carcinoma (HCC) indicate a significant association. 40 patients with chronic hepatitis were seen between 1975-79. 6/25 of chronic active hepatitis and 7/15 with chronic persistent hepatitis were HBsAg positive (RIA). In the 41 patients with HCC, 15 (37%) were alcoholic, 10 cirrhosis (HBsAg positive), 5 haemochromatosis 5 cryptogenic cirrhosis, 2 probably due to sex steroids and in 4 no aetiological factor was apparent. HBsAg was present in 10/22 (45%) of HCC with cirrhosis, 15/256 (6%) for alcoholic cirrhosis, 5/16 (33%) for haemachromatosis and 5/30 (16%) cryptogenic cirrhosis. 8/80 (10%) who had acute viral hepatitis (B) are antigen positive at 6 months. This report shows that Hepatitis B virus infection is now a significant causes of liver injury in 180 patients studied. The majority of patients who have HBsAg positive cirrhosis do not have a history of acute hepatitis. PMID- 6252813 TI - Relationship between histology and aetiological factors in primary liver cancer. AB - A review of 205 primary hepatic cancers from different geographic areas reveals that HCC which forms the vast majority (86%) of these, commonly presents as the trabecular variety (76%). The compact and pseudoglandular forms are rare (18% and 6%). Relatively fewer cases of undifferentiated cancer, hepatoblastoma and cholangiocarcinoma are encountered. HCC is often associated with the presence of hepatitis B virus surface antigen (HBsAg) in the liver. This is particularly true of the trabecular variety (81%). A proportion of the compact variety as well as undifferentiated cancers do not appear to be related to HBV infection. Cholangio carcinomas are considered to be related to infection by liver flukes. Hepatoblastomas occur in infancy and childhood and show no known aetiologic association. Aflatoxin may be aetiologically related to same cases of HCC. Continued use of oral contraceptives can occasionally induce HCC. PMID- 6252814 TI - Radiological diagnosis of hepatocellular carcinoma. AB - Recent radiological procedures for the diagnosis of hepatocellular carcinoma and other liver malignancies, such as radionuclide scanning, coeliac angiography, ultrasonography and computed tomography, are discussed, particularly with respect to the diagnostic accuracy of the individual procedures. Emphasis is also made of the possible angiographic assessment of gross anatomy of hepatocellular carcinoma, angiographic diagnosis of intravascular tumour growth, and the practical value of real-time ultrasonic linear scan such as ultrasonically guided needle aspiration of the tumour cytology. PMID- 6252815 TI - A pilot study on the screening of primary hepatocellular carcinoma in selected high risk groups in the population using multiple tumour markers. AB - A prospective one year study on groups of 377 high risk individuals was done using alphafoetoprotein (AFP), alpha 1antitrypsin (A1AT), alpha 1 acidglycoprotein 1 (A1GP), gammaglutamyltraspeptidase (GGT) and isocitrate dehydrogenase (ICD) to detect hepatocellular carcinoma (HCC). The high risk groups screened were: cirrhosis, unexplanable hepatomegalies, chronic hepatitis B surface antigen (HBsAg) carrier, family members of afflicted HCC cases, individuals on hormonal therapy and males over the age of 30 years. 58/377 (15%) were found to have HCC. This consisted of 16/43 (37%) clinical cirrhosis, 40/71 (56%) unexplanable hepatomegalies, 1/33 (3%) chronic HBsAg, 1/156 (0.6%) family members. AFP remained the most useful test but the others such as A1AT, A1Gp, GGT and ICD recognised both malignant and asymptomatic nonmalignant diseases. Only 4 (7%) patients had resectible tumours detected and 1 patient was found to have liver dysplasia. HBsAg positivity and persistently raised AFP. The significance of HBsAg amongst family members and other group is discussed in terms of genetic susceptibility, environmental oncogenic vulnerability and ultimate screening. PMID- 6252816 TI - Adriamycin in the treatment of resectible and irresectible primary hepatocellular carcinoma. AB - The treatment of 205 patients with primary hepatocellular carcinoma in Singapore from 1975 to 1980 is reviewed. Adriamycin given at a dose of 40 mg/m(2) intravenously every 4 weeks for irresectible tumours achieved a response rate of 32% alone and has significantly prolonged the median survival time to 4 1/2 months (135 days) in these individuals. Despite this response only 1/34 (3%) patient showed complete remission and is alive at 2 1/2 years. Use of other combinations with Adriamycin e.g. 5 Fluorouracil and Vincristine produced a significant response in the first 16 weeks (p < 0.005) but not thereafter, when completed with the historical group. To improve the response and to consolidate this response, split doses of total hepatic irradiation (to a maximum of 3,150 rads) and alternate day administration of intravenous Adriamycin 10 mg (to a maximum of 90 mg) were given. 12/23 patients (50%) responded. This was followed by a four weekly Adriamycin, 5 F.U. and Vincristine. Median survival time was 5 1/2 months (165 days). Relapse occurred in all patients. Similarly in 5 patients who had resections, early recurrences occurred in 3/5 (60%) within 3 months, inspite of postoperative chemotherapy with Adriamycin, 5 F.U., Vincristine and Cyclophosphamide given every four weeks. In view of the high recurrence rate following effective treatment, further studies on the biological behaviour of these abnormal livers is required. PMID- 6252817 TI - Therapy of hepatocellular cancer with combined intrahepatic arterial chemotherapy and whole liver irradiation. AB - Hepatocellular cancer provides an ideal model for studying combined modality chemotherapy and radiation interactions. We have treated 20 evaluable patients. All patients received intrahepatic arterial (IA) 5 FU (10 mg/kg/d continuous infusion times 5 minus 9 d) + Adriamycin (3-5 mg/m(2)/d bolus times 5 minus 7 d), and 1,500 and 2,100 rads whole liver radiation (300 rads/day). Additionally, 3 patients have received IA Mitomycin C (8 mg/m(2)). After this "induction" therapy patients usually received IV Adriamycin + 5FU +/- Mitomycin monthly. Objective regressions occurred in 9/20 (45%) and another 9/20 (45%) and stable disease. Median duration of response is 5+ months (range 1+ to 8 months). Improvement in liver function tests occurred in 11/19, and local symptomatic relief in 12/15. Median WBC nadir = 4,000; platelet nadir = 115,000. Mild anorexia, fever, and nausea were frequent, but no radiation hepatitis has been detected. This program seems to result in significant clinical benefit (subjective and objective) in this refractory neoplasm. PMID- 6252818 TI - The indications for and results of liver transplantation. AB - The overall indications for liver transplantations are becoming clearer. Patients with decompensated cirrhosis are poor risks and grafting should be done earlier. Results of transplants for primary biliary cirrhosis and well compensated cirrhosis are more encouraging. Transplantations for hepatocellular carcinoma is faced with the problem of high recurrences postoperatively. The presence of hepatitis B in a recipient is no longer a contraindication to grafting since this can be adequately treated with specific immunoglobulin. The latest introduction of Cyclosporin as an immunosuppressant may be of real benefit in liver transplantations. PMID- 6252819 TI - Prenatal diagnosis of thalassemias and hemoglobinopathies. AB - Thalassemia syndromes and hemoglobinopathies are of clinical genetic significance because of the severity of the sequelae associated with particular genetic constitutions in these conditions, their occurrence at high frequencies in certain populations of Mediterranean, African, and Asian origin, and the high frequency of recurrence in pregnancies of at risk families. Application of recently developed techniques of molecular genetics to the antenatal diagnosis of the most deleterious of these conditions (homozygous beta-thalassemia [Cooley's anemia], homozygous alpha-thalassemia [Barts hydrops fetalis], sickle cell anemia, and related severe homoglobinopathies) now affords parents the option to interrupt a pregnancy in which the fetus has the genetic constitution causing one of these abnormalities. The two different analytical strategies utilize fetal cells obtained by aminocentesis. In one, fetal blood is obtained either by sonographically guided placental aspiration or by aspiration from a placental vein directed by fetoscopy. Globin chain synthesis is monitored by the incorporation of radiolabelled amino acids in the isolated erythrocytes and the determination of the ratio of radioactive label incorporated into the various globin chains separated by column chromatography or electrophoresis. This technique is applicable to the antenatal diagnosis of alpha-and beta-thalassemia and to selected hemoglobinopathies. However, in the most experienced centers, fetal blood sampling is associated with a greatly increased risk of fetal loss. The other analytical approach utilizes desoxyribonucleic acid (DNA) isolated from fibroblasts to evaluate the presence of quantitatively and/or qualitatively normal DNA sequences, which constitute the structural gene(s) encoding specific globin polypeptide chains. This approach is most generally applicable to the detection of structural gene deletions as in a alpha-thalassemia; maternal and fetal risk is the same as that for conventional amniocentesis. PMID- 6252821 TI - Regional assignment of catalase (CAT) gene to band 11p13. Association with the aniridia-Wilms' tumor-Gonadoblastoma (WAGR) complex. AB - A gene dosage effect for catalase (CAT) was investigated in three individuals : one with 11p13 deletion, aniridia, ambiguous genitalla, and gonadoblastoma ; one trisomic for 11p with the exception of 11p13; and one trisomic for 11p13. Results were compatible with the assignment of CAT to 11p13 and its linkage with the aniridia-gonadoblastoma or Wilms' tumor complex (WAGR). PMID- 6252822 TI - A simple screening procedure for adenylate kinase, hexokinase and glucose-6 phosphate dehydrogenase deficiencies. AB - A simple screening procedure for the detection of adenilate kinase (AK), hexokinase (Hx) or glucose-6-phosphate dehydrogenase (G6PD) deficiencies in blood, is described. It consists of two assays : in the first, the ATP formed by blood AK is coupled to Hx and G6PD, and in the second, the glucose-6-phosphate formed by blood Hx is coupled to G6PD. The enzyme activities are visually estimated by the reduction of NADP+ (non-fluorescent) to NADH (fluorescent). The appearance of fluorescence in the first assay indicates that the three enzyme activities are present. The absence of fluorescence could be due to the deficiency of any one of the three enzymes; in this case the second assay used in combination with the Beutler's screening test for G6PD permits the detection of the specific enzymatic deficiency. PMID- 6252820 TI - Clinical consequences of enzyme deficiencies in the erythrocyte. AB - The anucleate mature erythrocyte also lacks ribosomes and mitochondria and thus cannot synthesize enzymes or derive energy from the Krebs citric acid cycle. Nevertheless, the red blood cell is metabolically active and contains numerous residual enzymes and their products which are essential for its survival and normal functioning. Enzyme deficiencies in the Embden-Myerhoff glycolytic pathway can result in nonspherocytic hemolytic anemia (NSHA), and some are also associated with neuromuscular or neurologic disorders. Glucose-6-phosphate dehydrogenase deficiency in the hexose monophosphate shunt also results in hemolytic anemia, especially following exposure to various drugs. Defects in glutathione synthesis and pyrimidine 5'-nucleotidase deficiency also cause NSHA, as does increased adenosine deaminase activity. Gluthathione synthetase deficiency which is not limited to the red cell also presents as oxoprolinuria with neurologic signs. All red cell enzyme defects appear as single gene errors, in most cases recessive in inheritance, either autosomal of X-linked. PMID- 6252823 TI - Neurotonia: impulse-induced repetitive discharges in motor nerves in peripheral neuropathy. AB - Delayed relaxation of muscle following voluntary contraction was an unusual feature of a mild chronic sesorimotor peripheral neuropathy in an adult. This abnormality resulted from rapid repetitive discharges in motor nerves occurring only in response to passing impulses; there was no spontaneous nerve discharge. Voluntary contraction of affected muscles generated involuntary high-frequency discharges of motor unit potentials, which persisted briefly after attempted relaxation. Nerve blocks localized independent zones of hyperexcitability in distal and proximal sections of nerve from which such repetitive discharges could be triggered. Intravenous administration of phenytoin diminished the discharge. Examination of intramuscular nerve bundles revealed loss of myelinated nerve fibers with numberous sprouting and remyelinating axons. These findings, along with muscle biopsy changes of neurogenic atrophy and type grouping, strongly favor an axonal neuropathy. An explanation for the repetitive nerve discharge is slow waning of heightened excitability of a motor nerve after passage of an impulse. PMID- 6252824 TI - Pure axonal neuropathy: nerve xenografts and clinicopathological study of a family with peripheral neuropathy, hereditary ataxia, focal necrotizing encephalopathy, and spongy degeneration of brain. AB - Three family members had the unusual combination of severe peripheral neuropathy, atypical hereditary ataxia, spongy degeneration of cerbral hemispheres, and cerebellar and brainstem foci of necrotizing encephalopathy, proved pathologically in one autopsied case. A sural nerve from a patient, devoid of myelinated fibers, was transplanted into thymectomized, lethally irradiated, and bone marrow reconstituted adult mice. A normal number of myelinated fibers was present in the grafts eleven weeks later. Eighteen weeks after grafting, mice were reconstituted with syngeneic thymus to return immunocompetence. Schwann cells in the graft were rejected and axons became totally denuded of myelin after thymus reconstitution. The peripheral neuropathy is thus due to axonal disease since human Schwann cells were capable of normally myelinating regenerating mouse axons. A puzzling feature after rejection was the absence of myelin debris containing macrophages in the grafts. It is suggested that part of the rejection process in this model is mediated by antibody rather than by cellular mechanisms. PMID- 6252826 TI - [Isolation and characteristics of polymyxin-resistant mutants of Shigella flexneri]. AB - Some characteristics of S. flexneri 2a mutants resistant to various concentrations of polymyxin M were studied. The data indicate that mutations resulting in low (50 microgram/ml) and high (300 microgram/ml) levels of the antibiotic resistance were determined by different genes. Polymyxin resistance led to changed permeability of the outer membrane with respect to detergents and some antibiotics, such as aminoglycosides, penicillins, chloramphenicol and amphotericin B but did not change sensitivity of the strains to some bacteriophages, except phage PI. Mutants resistant to 50 microgram/ml of polymyxin M preserved their ability to induce keratoconjunctivitis in guinea pigs. Part of the strains resistant to 300 microgram/ml of the antibiotic lost this property. No correlation between the polymyxin M resistance level, loss of the pathogenic properties and toxicity of the bacterial cells was found. It was confirmed that though inactivation of endotoxin by polymyxins is associated with their capacity for interaction with lipid A, this component does not participate in development of resistance to these antibiotics. PMID- 6252825 TI - Neuropathy and mitochondrial myopathy. AB - It has been stated that peripheral neuropathy can be a feature of so-called ophthalmoplegia-plus syndrome, but to date only one case of hypertrophic neuropathy has been reported. This study is concerned with the clinical, electrophysiological, and pathological observations in a 37-year-old man with progressive external ophthalmoplegia and a ragged-red fiber myopathy associated with severe sensorimotor neuropathy. Histological and morphometric studies of the sural nerve revealed a marked loss of large myelinated fibers and an occasional degenerating axon. Residual fibers had disproportionately thin myelin sheaths in relation to axon calibers. In contrast to the muscle biopsy findings, no mitochondrial paracrystalline inclusions were observed in the nerve. However, the number of mitochondria per square micron of Schwann cell cytoplasm was elevated when compared with values obtained from normal subjects and a patient with a chronic neuropathy. These findings may indicate an alteration of mitochondrial function common to muscle fibers and Schwann cells which, in nerves, could lead to axon loss and abnormality of myelination. PMID- 6252827 TI - [Auxotrophic mutations formed on the incorporation into the E. coli C600 chromosome of transposon Tnl that determines ampicillin resistance]. AB - Incorporation of transposone Tnl of ampicillin resistance into the chromosome of E. coli C600 resulted in formation of at least 8 types of auxotrophic mutants. The transposone incorporates mainly into the loci the damage of which induces proline deficit (20 per cent). The sites of incorporation of transposone Tnl in the chromosomes of E. coli C600 and E. coli JC411 did not coincide. PMID- 6252828 TI - [Trial of the clinical use of mithramycin in treating testicular cancer]. AB - The data on efficacy of mitramycin, an antitumor antibiotic in treatment of 32 patients with cancer of the testicle are presented. The objectively pronounced effect was observed in 37.5 per cent of the cases, mitramycin being effective in patients with tumors resistant to bleomycin, vinblastin and cis dichlordiaminoplatinum. Nausea and vomiting were the most frequent side effects of mitramycin use. The hemorrhagic syndrome was recorded in 2 patients. The regimen of the mitramycin intravenous administration in a dose of 25--30 microgram/kg once in 2 days was well tolerated by the patients and may be recommended for the treatment of testicle cancer. PMID- 6252829 TI - Comparative in vitro activities of cefotaxime and ceftizoxime (FK749): new cephalosporins with exceptional potency. AB - Cefotaxime and its desacetoxymethyl derivative, ceftizoxime (previously known as FK749), are both extremely active against a wide spectrum of bacteria. In the present comparative study, the activity of ceftizoxime exceeded that of cefotaxime by a factor of four or more for strains of Klebsiella, Enterobacter, Providencia, Serratia, and Bacteroides; the only species for which the activity of cefotaxime exceeded that of ceftizoxime by a factor of four was Vibrio cholerae. Against other species, the activity of the two drugs was roughly comparable. Both showed outstanding activity against Haemophilus influenzae and Neisseria gonorrhoeae. Comparative turbidimetric and morphological studies revealed that ceftizoxime was able to induce spheroplast formation and rapid lysis in Escherichia coli strains at lower concentrations than cefotaxime. This difference was not found, however, when E. coli strains resistant to ampicillin by an intrinsic (nonenzymic) mechanism were tested. PMID- 6252830 TI - Activity of cefotaxime-aminoglycoside combinations against aminoglycoside resistant Pseudomonas. AB - The activity of cefotaxime, either alone or combined with an aminoglycoside, was determined against 50 isolates of Pseudomonas aeruginosa, of which 50, 33, and 10 were resistant to gentamicin, tobramycin, and amikacin, respectively. Cefotaxime inhibited 34 isolates at a concentration of 16 microgram/ml and all isolates at 128 microgram/ml. The combinations of cefotaxime with gentamicin, tobramycin, and amikacin were synergistic against 30, 17, and 9 isolates, respectively, and no antagonism was observed with any combination. Synergism was obtained at clinically significant antibiotic concentrations for nine isolates with cefotaxime-gentamicin, five isolates with cefotaxime-tobramycin, and nine isolates with cefotaxime-amikacin. PMID- 6252831 TI - Comparison of cefoperazone, cefotaxime, and moxalactam (LY127935) against aerobic gram-negative bacilli. AB - This study compares the minimum inhibitory concentrations of cefoperazone, cefotaxime, and moxalactam (LY127935) for 446 aerobic gram-negative bacillary isolates and further compares the minimum inhibitory concentrations of LY127935 and these third-generation cephalosporins with those of thienamycin for Pseudomonas aeruginosa. Each antibiotic at low concentrations inhibited nearly all Enterobacteriaceae tested. Minimum inhibitory concentrations for P. aeruginosa were higher, but for a majority of strains they fell below achievable serum levels. Thienamycin and cefoperazone showed significantly greater antipseudomonal activity than did cefotaxime or LY127935. Cefoxitin-inducible resistance to LY127935 and the two cephalosporins was demonstrated among Enterobacter species but did not occur with thienamycin. PMID- 6252832 TI - In vitro activities of cefotaxime and moxalactam (LY127935) against Haemophilus influenzae. AB - The in vitro activities of two new beta-lactam antibiotics, cefotaxime and moxalactam (LY127935), were compared with those of cefamandole, cefoxitin, cefuroxime, and ampicillin against both beta-lactamase-producing and non-beta lactamase-producing isolates of Haemophilus influenzae. Both cefotaxime and LY127935 were highly active against all isolates irrespective of beta-lactamase production. PMID- 6252833 TI - Comparison of cefotaxime and moxalactam pharmacokinetics and tissue levels. AB - The pharmacokinetics of cefotaxime and moxalactam were compared in six healthy male volunteers aftr the administration of 1-g doses intravenously. Penetration of the compounds into tissue fluid was studied in cantharides-induced blisters. Both serum and tissue fluid levels of moxalactam were higher than those of cefotaxime. The elimination half-life of cefotaxime was 1.2 h, and that of moxalactam was 2.85 h. On the average, 50.5% of cefotaxime and 87.5% of moxalactam were recovered in the urine in 24 h. PMID- 6252834 TI - 5'-Amino-5'-deoxythymidine: synthesis, specific phosphorylation by herpesvirus thymidine kinase, and stability to pH of the enzymically formed diphosphate derivative. AB - Radioactive 5'-amino-5'-deoxythymidine (5'-AdThd), an inhibitor of herpes simplex virus, was synthesized by direct amination of monotosylated thymidine with concentrated ammonium hydroxide. Incubation of 5'-AdThd with purified herpes simplex virus type 1-encoded pyrimidine deoxyribonucleoside kinase produced the diphosphate derivative. The monphosphate derivative of 5'-AdThd was not detected as a reaction product of this enzymatic phosphorylation. A purified mixture of nonviral thymidine kinase and thymidylate kinase derived from uninfected Vero cells was unable to phosphorylate 5'-AdThd under identical conditions. The rate of hydrolysis of 5'-AdThd diphosphate increased as the pH of the reaction mixture decreased, with a shoulder region appearing between pH 3 and 5. The rate of hydrolysis was markedly increased below pH 3. 5'-AdThd, but not the monophosphate derivative, was detected in the hydrolysis mixture. The hydrolysis of 5'-AdThd diphosphate pH 3 also yielded some thymine in addition to 5'-AdThd. PMID- 6252835 TI - Carbenicillin plus cefazolin with or without mecillinam as an early treatment of bacteremia caused by gram-negative organisms: randomized double-blind study. AB - Mecillinam or a placebo was added to a combination of cefazolin and carbenicillin as an early therapy of septicemia caused by gram-negative organisms in patients with serious underlying diseases, none of whom was neutropenic, however. Patients in whom infection was caused by pathogens against which mecillinam and cefazolin or mecillinam and carbenicillin were synergistic might have responded more often than patients treated with nonsynergistic combinations. However, overall results did not show any benefit from combining mecillinam with cefazolin and carbenicillin. This study suggests that in nonneutropenic patients with septicemia caused by gram-negative organisms, there is no need to intensify antimicrobial therapy beyond a certain point of efficacy. The measurement of the bactericidal activity in the serum of treated patients might serve as guide for adequate therapy. PMID- 6252836 TI - In vitro susceptibility of varicella-zoster virus to acyclovir. AB - The in vitro susceptibility of five strains of varicella-zoster virus to acyclovir was examined by the plaque-reduction method in human diploid lung cells. The 50% effective doses of acyclovir ranged from 2.06 microM to 6.28 microM in a 7-day assay, with a mean of 3.65 microM. Irreversible inhibition of plaque formtation was achieved by drug doses exceeding the 50% effective dose for plaque reduction but nontoxic to the cells. Studies on the relative in vitro susceptibility of varicella-zoster virus and herpes simplex virus types 1 and 2 to acyclovir suggested that varicella-zoster virus is two- to eightfold less susceptible to the drug. The antiviral potency of acyclovir for varicella-zoster virus in vitro was compared with that of several other nucleoside analogs. Analysis of the metabolism of acyclovir in varicella-zoster virus-infected WI-38 cells revealed that, as with herpes simplex virus types 1 and 2, the formation of the triphosphate forms of the drug is specific to viral infection. PMID- 6252837 TI - In vitro susceptibility of gram-negative bacilli from pediatric patients to moxalactam, cefotaxime, Ro 13-9904, and other cephalosporins. AB - Moxalactam, Ro 13-9904, cefotaxime, cefoperazone, older cephalosporins, and four aminoglycosides were tested in vitro against 432 strains of gram-negative bacteria isolated from pediatric patients. The new drugs were uniformly active against coliform bacilli obtained from patients with meningitis and against aminoglycoside-resistant coliform bacilli. PMID- 6252838 TI - Inhibition of the glycogen phosphorylase system during ochratoxicosis in chickens. AB - Graded doses of ochratoxin A incorporated into the diet (0, 0.5, 1.0, 2.0, 4.0, and 8.0 micrograms/g) of broiler chickens significantly (P < 0.05) inhibited activity of protein kinase, the initiator enzyme of the glycogen phosphorylase system, in the livers at all dose levels. Only the highest dose, 8.0 micrograms/g, significantly reduced the total activity of phosphorylase kinase, which is activated by protein kinase. The total activity of phosphorylase, which is activated by phosphorylase kinase, was unaltered by ochratoxin A at any level. Additon of ochratoxin A to liver extracts control birds inhibited protein kinase but not phosphorylase kinase. When added to extracts of livers from control birds, cyclic adenosine 3',5'-monophosphate stimulated protein kinase but not phosphorylase kinase. The cyclic adenosine 3',5'-monophosphate had no effect when added to extracts from birds fed ochratoxin A. These results suggest that ochratoxin A affects primarily the cyclic adenosine 3',5'-monophosphate-dependent protein kinase which initiates the enzymatic cascade leading to glycogenolysis. Furthermore, these results conform an earlier assignment on morphological criteria of the glycogenosis of ochratoxicosis as a type X glycogen storage disease. PMID- 6252839 TI - Inactivation of coxsackieviruses B3 and B5 in water by chlorine. AB - The inactivation rates of coxsackievirus B3 (CB3) and B5 (CB5) by chlorine in dilute buffer at pH 6 were very nearly the same and about half that of poliovirus (Mahoney) under similar conditions. Purified CB3, like the poliovirus, aggregated in the acid range but not at pH 7 and above. Purified CB5 aggregated rapidly at all pH values; still, the graph of log surviving infectivity versus time was a straight line. No chlorine inactivation data were obtained with dispersed CB5, for it could be dispersed only by addition of diethylaminoethyl dextran, which would react with the chlorine. Addition of 0.1 M NaCl to the buffer at pH 6 did not influence the aggregation of CB5 or the rate of chlorine action on either of the coxsackie-viruses, but at pH 10 it increased the disinfection activity of OCl for both viruses roughly 20-fold. Cesium chloride had a similar but smaller effect. KCl was the most active of the three in this respect, making the inactivating effect of OCl- at pH 10 about equal to that of HOCl at pH 6. PMID- 6252840 TI - Laboratory studies of disinfectants against Legionella pneumophila. AB - Legionella pneumophila suspended in tap water was exposed to biocides recommended for inhibiting biological growth in cooling towers and evaporative condensers of air-conditioning systems. Chlorine, 2,2-dibromo-3-nitrilopropionamide, and a compound containing didecyldimethylammonium chloride and isopropanol were effective in destroying concentratiois of 10(5) to 10(6) viable cells per ml. Formulations consisting of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4 isothiazolin-3-one, disodium ethylene bis(thiocarbamate) and sodium dimethyl dithiocarbamate, and a phenolic with pentachlorophenate and sodium salts of other chlorophenols were less effective. PMID- 6252842 TI - A ribonuclease specific for double-stranded RNA and two distinct ribonuclease H activities from the ribosomal salt wash fraction of Ehrlich ascites tumor cells. PMID- 6252843 TI - The role of interactions between O2, H2O2, .OH,e- and O2- in free radical damage to biological systems. PMID- 6252841 TI - Effect of Escherichia coli endotoxin on adenine nucleotide translocation in canine heart mitochondria. PMID- 6252844 TI - Stimulation of rat liver cyclic 3':5'-nucleotide phosphodiesterase by cyclic GMP is dependent on enzyme concentration. PMID- 6252845 TI - Deglycosylation of ovine pituitary lutropin subunits: effects on subunit interaction and hormone activity. PMID- 6252846 TI - Effect of crosslinking cytochrome c oxidase. PMID- 6252847 TI - Characteristics of the nucleotide phosphohydrolases of hamster embryo cells. PMID- 6252848 TI - Immobilization of nucleoside diphosphatase at its allosteric site using immobilized derivatives of pyridoxal 5'-phosphate. PMID- 6252849 TI - S1 nuclease of Aspergillus oryzae: a glycoprotein with an associated nucleotidase activity. PMID- 6252850 TI - Isolation of a new metabolite of vitamin D produced in vivo, 1 alpha,25 dihydroxyvitamin D3-26,23-lactone. PMID- 6252851 TI - Evidence of ubisemiquinone radicals in electron transfer at the cytochromes b and c1 region of the cardiac respiratory chain. PMID- 6252852 TI - Vitamins and alopecia. PMID- 6252853 TI - Ketoconazole treatment of chronic mucocutaneous candidiasis. AB - Five patients received ketoconazole treatment of chronic mucocutaneous candidiasis. One also had disseminated histoplasmosis and cryptococcosis. Ketoconazole was well absorbed after an oral dose of 200 mg and produced detectable antifungal blood levels for more than eight hours after each dose. Thrush cleared in less than two weeks in all patients. Cutaneous lesions cleared slowly during several months of treatment. A patient with polymycotic infection had a rapid clearing of candidiasis, but her histoplasmosis did not respond to three weeks of treatment. Adverse drug effects were minimal. Ketoconazole is a promising new agent for treatment of chronic mucocutaneous candidiasis. PMID- 6252854 TI - Vasculitis in cytomegalovirus infection. AB - A 7-year-old girl had fever, arthralgia, and a mild cutaneous vaculitis with papules, nodules, and livedo. A biopsy specimen of a papule showed lymphocytic small-vessel vasculitis, with some atypical lymphocytic nuclei. Splenomegaly developed, and results of subsequent studies supported a diagnosis of cytomegalovirus (CMV) infection, with atypical peripheral blood lymphocytes and a characteristic pattern of complement-fixing antibodies to CMV antigen. The CMV mononucleosis syndrome is rarely reported in children, and the cutaneous manifestations are usually rubelliform. Distinctive cutaneous pathologic characteristics have been described previously only in neonates ("blueberry muffin" syndrome) and in immunosuppressed patients (viral inclusion bodies in endothelial cells). PMID- 6252855 TI - [Light-microscopic study of classified virus warts (HPV-1 and HPV-4) (author's transl)]. AB - Histological investigations of verrucae vulgares of the hand and of plantar warts show striking differences between HPV-1-induced warts and those caused by the virus type HPV-4. In warts caused by HPV-1 massive vacuolization and disturbance of epidermal cell differentiation through the entire thickness of the epidermis is predominant whereas in HPV-4 stimulated warts cell differentiation is impaired to a much lesser degree. Despite the presence of inclusions and of vacuolized cells a thick stratum granulosum and a compact horny layer are formed in the latter type. PMID- 6252856 TI - Selection by mediastinoscopy and long-term survival in bronchial carcinoma. AB - In order to reduce the high rate of inoperability in patients with bronchial carcinoma, mediastinoscopy was carried out as a routine preoperative selection in 874 patients during 13 years. Two hundred thirty-six patients (27%) were found to have involved lymph nodes at mediastinoscopy and were not treated surgically. Follow-up data were available on 210 of them: 165 (79%) died within a year, 16 survived for 2 years, and 4 for 5 years. Pulmonary resection was carried out in 638 patients. Five-year survival in the series was 24.5% and 10-year survival (based on 104 eligible patients), 16.3%, including the operative mortality of 5.5%. Mediastinoscopy has not improved long-term survival to any great extent. However, it has raised the rate of resectability to 97.1% and lowered the operative mortality without denying the patient a chance of cure. PMID- 6252857 TI - Perioperative myocardial infarction: a diagnostic dilemma. AB - Patients undergoing coronary bypass grafting were studied for incidence of perioperative myocardial infarction (MI) using three modalities: serial electrocardiograms (ECG), serial creatine phosphokinase isoenzymes (MB-CPK), and serial technetium 99m-labeled pyrophosphate scans. A definite perioperative MI was diagnosed if the results were positive in two of the three variables studied. The perioperative infarction rate for the entire group was 8%. The operative mortality was 2.9%. Seven of 8 perioperative MIs were diagnosed by the use of scanning alone. The combination of isoenzyme and ECG analysis diagnosed 5 of 8 perioperative MIs. The MB-CPK and ECG studies were associated with a higher incidence of false-positive diagnoses than myocardial scanning. Patients with perioperative MI had a benign clinical course. Justification for performing three routine 99mTc-pyrophosphate scans on all patients undergoing aortocoronary bypass operation is still to be determined. PMID- 6252858 TI - FSH-response adenylyl cyclase in rat testes: desensitization by homologous hormone. AB - Injection of high doses of FSH causes a partial desensitization of the FSH responsive adenylyl cyclase (AC) in adult rat testes. The loss of responsiveness to FSH is dependent on time. Two hours after injection of one dose of human FSH (256 micrograms hFSH-PT2) in vivo, no effect was seen on FSH-stimulated AC activity (Km and maximal activation). After 24 hr there was an approximately 40% decrease in FSH activated AC. Injection of two doses of FSH (256 micrograms hFSH PT2) 24 and 48 hr before being killed, gave a loss in FSH-responsive AC activity of approximately 60%. The decreased FSH-stimulated AC activity after FSH injections in vivo was associated with a comparable decrease in specific FSH binding. Whether this is a reflection of receptor occupancy or down regulation of the number of FSH receptors is not known. Desensitization of the FSH-responsive AC caused by FSH was not associated with a change in its Km. PMID- 6252859 TI - Remission of pituitary-dependent Cushing's disease after removal of nonneoplastyic pituitary gland. AB - Transsphenoidal hypophysectomy was performed on a 28-year-old woman with pituitary-dependent Cushing's disease. Both clinical and chemical resolution of the hypercortisolism was achieved in spite of no evident pituitary microadenoma or cell hyperplasia. Histologic examination revealed widespread Crooke's changes and normal relative numbers, size, and distribution of corticotrophs. We propose that rare patients with pituitary-dependent Cushing's disease may have excessive pituitary production of adrenocorticotropic hormone in the absence of an adenoma or corticotroph cell hyperplasia. PMID- 6252860 TI - Cell mediated immune responses in experimental amebiasis. AB - Cell migration was inhibited when Entamoeba histolytica antigen-sensitized peritoneal exudate cells were cultured in the presence of specific antigen. The inhibition of cell migration was caused due to interaction of antigen with sensitized lymphocytes. This migration inhibition was well correlated with cell mediated immune responses, but not with circulating antibody levels. Peritoneal cells obtained from animals immunized with 70.5 microgram of antigen gave a better response in capillary tube tests. It was further found that 0.88 microgram antigen constitutes an optimum dose for studying migration inhibition reaction. The results obtained from the capillary and agarose plate technics show a slight disparity due to a difference in the respective specificities of the two tests. Agarose plate technic appears to be rather specific for pure antigen samples, while the capillary tube test is more appropriate for crude type antigens. PMID- 6252861 TI - Sequential histopathology of cavitary liver abscess. Formation induced by axenically grown Entamoeba histolytica. AB - Multiple hamster liver passage of Entamoeba histolytica trophozoites with intervening recovery into axenic culture caused increased virulence as measured by increase in the size of the lesion produced. Lesions produced by amebae that had not been liver-passaged did not persist; however, multiply liver-passaged substrains produced large, fluid-filled abscesses one month to six weeks after inoculation. Six days after inoculation, lesions consisted of multiple granulomas, lymphocytes, and E histolytica trophozoites. Large, fluid-filled abscesses produced by liver-passaged substrains lacked the granulomatous appearance of the earlier lesions. The abscesses had a fibrous wall, with E histolytica trophozoites at the inner aspect. To our knowledge, the evolution of early granulomatous lesions into a cavitary abscess with features closely resembling those of human amebic abscess has not been reported previously in the experimental disease in the hamster. PMID- 6252862 TI - Cytomegalovirus inclusion disease. Its occurrence in the myenteric plexus of a renal transplant patient. AB - Cytomegalovirus (CMV) infected the myenteric plexus of the small and large bowels in an 18-year-old renal transplant patient. This is, to our knowledge, a previously unreported condition. The patient died of a massive gastrointestinal hemorrhage, which possibly resulted from a series of CMV cecal ulcers associated with Candida fungal hyphae and spores. PMID- 6252863 TI - [Influence of various physical forms of the feed on the energy metabolism of ruminants. 3. Investigation of the energetic utilisation of rations with roughage treated with various mechanical methods]. AB - In a total of 170 experiments with the complete metabolism of fullgrown sheep the energy utilisation of rations with roughage treated with different mechanical methods was investigated. The roughage feedstuffs dried green fodder of vetch/grass, lucerne and rye grass and straw were given to 4 parallel animals in 9 rations with differing quotas of concentrates (0 to 60%). The roughage underwent the following 5 methods of treatment: 1) chopping; 2) chopping and pelleting; 3) grinding; 4) grinding and pelleting; 5) grinding and pelleting with concentrates. The results show that the bases given in the GDR system of feedstuff evaluation concerning the energetic evaluation of feedstuffs are to be applied to mechanically treated roughage too. In order to avoid negative effects on the energy metabolism one has to take care that the use of mechanically treated roughage does not cause dysfunctions of the rumen. PMID- 6252864 TI - Efficacy of a nucleic acid free herpetic subunit vaccine. AB - The efficacy of immunization with an herpes simplex subunit vaccine, free of nucleic acid, was evaluated in mice, rabbits and monkeys. One injection of 3 micrograms per kg of body weight elicited both humoral and cell-mediated immunity in all the animals studied. Furthermore, the immunization reduced significantly the mortality to a subsequent challenge with live herpes simplex virus in mice and rabbits (p less than 0.01). PMID- 6252865 TI - DNA synthesis in chromatin preparations from human fibroblasts infected by cytomegalovirus. AB - Chromatin prepared from (14C)-thymidine pulse labelled cytomegalovirus-infected human fibroblasts 72 hours postinfection exhibited under appropriate conditions endogenous activity of (3H)-thymidine triphosphate incorporation which was relatively salt-resistant and phosphonoacetic acid-sensitive. Isopycnic centrifugation of the doubly labelled DNA in CsCl revealed that cell-free incoporation occurred into viral as well as into host cell DNA. Density labelling experiments with bromodeoxyuridine triphosphate suggested the incoporation into viral DNA to be due to replicative DNA synthesis. Chromatin from infected cells contained, in addition to cellular, viral DNA polymerase activity. PMID- 6252866 TI - The molecular weight of the egg drop syndrome (EDS) avian adenovirus (strain B8/78) DNA estimated by digestion with restriction endonuclease enzyme R X EcoRI. Brief report. AB - The restriction endonuclease R X EcoRI cleaved at two sites of the EDS adenovirus (strain B8/78) DNA generating 3 fragments with molecular weights of 13.5 X 10(6), 5.0 X 10(6) and 4.4 X 10(6) daltons, respectively. The estimated molecular weight of the whole undigested DNA is about 22.9 X 10(6) daltons. PMID- 6252867 TI - Inhibition of herpesvirus multiplication in guinea pig skin by antiviral compounds. AB - The effects of adenine arabinoside, cytosine arabinoside, iododeoxyuridine, ribavirin, phosphonoacetate and phosphonoformate on virus titers in cutaneous herpesvirus infections of guinea pigs have been determined and compared to their effects on lesion score. Only phosphonoacetate and phosphonoformate caused a reduction in virus titer and lesion score when the drugs were applied topically after symptoms had developed. However, unlike phosphonoacetate, phosphonoformate did not cause local skin irritation. A herpesvirus mutant, inducing a DNA polymerase resistent to phosphonoformate gave rise to an infection in which the virus titer was not reduced by phsophonoformate. PMID- 6252868 TI - Establishment of rotavirus persistent infection in cell culture. Brief report. AB - Inoculation of the rabbit kidney cell line (RK13) with simian rotavirus SA11 resulted in persistently infected (carrier) cultures. A small percentage of these cells produced infectious virus (> 25 passages) and trypsin treatment enhanced virus production. PMID- 6252869 TI - Growth of murine cytomegalovirus in murine and heterologous brain cell cultures. Brief report. AB - Murine cytomegalovirus (MCMV) produced a cytopathic effect in mouse brain, guinea pig embryonic brain, human brain and fibroblast cells. Virus-specific antigen was detected by immunofluorescence in these cells after primary infection with MCMV. MCMV also replicated in ouse embryo brain and guinea pig brain cells. Although definite evidence of MCMV replication could not be demonstrated in human cells, MCMV infectivity was maintained for 12 days in human cell cultures. PMID- 6252870 TI - Modified radial-plaque-neutralization test for demonstration of enterovirus neutralizing antibodies. AB - A simple radial method based on the formerly described paper disc technique was developed for demonstration of neutralizing antibodies to enteroviruses with plaque forming ability. Sera administered by 5 microliter wire-loops to wells cut into the agar overlay of virus infected cell monolayers produced radial neutralization zones with a size directly related to their specific antibody contents. Results of poliovirus neutralizing antibody tests performed by the radial plaque neutralization method were found to be in a good agreement with those obtained in antibody titrations either in monolayer tube cultures or in microtitre system. The relatively simple technique makes possible to investigate several hundreds of serum samples in a single experiment, so it is especially suitable for use in expanded serological surveys. It proved to be useful also for identification of enteroviruses and for testing the laboratory strains for identity. PMID- 6252871 TI - Studies of glycoproteins from bovine aorta. AB - Glycoproteins from bovine aorta intima were isolated by a sequential digestion of the tissue with collagenase and elastase after extration of the tissue with saline. The proteins in the extracts were precipitated by (NH4)2SO4 and fractionated by Con-A sepharose affinity chromatography. The fractions were analyzed for their carbohydrate composition and by polyacrylamide disc gel electrophoresis. These studies show that considerable heterogeneity of aorta glycoproteins exists. Some of the glycoprotein materials are likely intimately associated with fibrous structures, collagen and elastin, of the aorta intima. PMID- 6252872 TI - The effect of arachidonic- and eicosapentaenoic acid on the synthesis of prostacyclin-like material in human umbilical vasculature. AB - All cis-5,8,11,14,17 eicosapentaenoic acid (EPA) inhibits platelet aggregation. The mechanisms for this inhibition are not known in detail. One of them might be a competitive inhibition of TXA2 production. Even if rat and human vasculature in pure systems covert EPA to PGI3 with the same properties as PGI2, it is essential to known if EPA influences the conversion of arachidonic acid (AA) to PGI2 in human vasculature. This problem was investigated in human umbilical vascular tissue deprived of substrate for PGI synthesis. After incubation with AA or EPA alone and in combinations, prostacyclin synthesis was measured as PGI2. Prostacyclin production in assays with AA and EPA in combinations in the incubation mixture, was found additive as calculated from assays with pure substrates. Thus, EPA did not influence the conversion of AA to PGI2 but gave obviously rise to additional synthesis of PGI-like material. PMID- 6252873 TI - [Hepatoblastoma in children]. AB - Five observations of hepatoblastoma in boys of 10 months to 4 years of age are presented. Tumor mass in the right part of the abdominal cavity was detected 1--9 months before death. Three patients died of pulmonary cardiac insufficiency, 2 of cateterization sepsis and hepatic insufficiency. The liver weight varied from 840 to 3500 g. Two children had intrahepatic metastases, one of them also had extrahepatic metastases into the portal lymph nodes and lungs. In 2 observations hepatoblastoma was of an epithelial structure, in 3 cases of a mixed type. It is suggested that hepatoblastoma, as well as liver carcinoma in adults, occurs more frequently in males. PMID- 6252874 TI - Comprehensive viral immunology of multiple sclerosis. II. Analysis of serum and CSF antibodies by standard serologic methods. AB - Sera and CSFs of 85 patients with multiple sclerosis (MS), 49 patients with probable MS, and 165 control patients with other neurologic diseases were assayed for antibodies to rubella, mumps, measles, parainfluenza I (strain 6/94), herpes simplex, cytomegalovirus, varicella-zoster, and vaccinia viruses. Methods included complement fixation (CF), hemagglutination inhibition (HI), and complement-dependent plaque reduction (CPR). Significant differences between the groups with MS and the control groups were higher serum antibody titers to measles virus in the groups with MS, higher proportion of patients with MS with CSF antibodies to measles, rubella, and vaccinia viruses, and greater percentage of patients with MS with more than one CSF viral antibody. Duration and severity of disease in the patients with MS were associated with presence of multiple CSF antibodies. Presence of CSF antibody was positively correlated with the height of the correspnding serum titer, yet a high serum titer did not ensure the presence of CSF antibody. Oligoclonal bands were present in the CSFs of equal proportions of patients with MS with and without CSF viral antibody. Our data support the hypothesis of local antibody synthesis within the CNS. However, we favor the view that preprogrammed antibody-forming lymphocytes enter the CNS and then produce antibody either because of nonspecific polyclonal activation in situ or because of failure of normal regulation. PMID- 6252875 TI - Comprehensive viral immunology of multiple sclerosis. III. Analysis of CSF antibodies by radioimmunoassay. AB - The CSF from 279 patients with multiple sclerosis (MS), probable MS, or controls was examined by radioimmunoassay (RIA) for antibodies to measles, rubella, mumps, parainfluenza 1 (Sendai) (strain 6/94), herpes simplex (HSV), varicella, and vaccinia viruses. Significantly more patients with MS than noninflammatory control patients had antibody to measles, rubella and varicella viruses, of which antibody to measles was the most prevalent. The percentage of patients with MS with two or more CSF antibodies was significantly greater than that in the controls. There was no tendency for certain antibodies to be associated. There was a general relationship between presence of CSF antibodies and severity of MS. The data support the hypothesis of local CNS antibody synthesis of several viral antibodies; however, such local synthesis may be a random event, possibly dependent on the number and specificity of peripheral virus antibody-forming lymphocytes available for ingress into the CNS. PMID- 6252876 TI - Multiple sclerosis de novo CNS IgG synthesis. Effect of CNS irradiation. AB - Megavoltage CNS irradiation was given to 20 patients with clinically definite multiple sclerosis (MS) to determine if de novo CNS IgG synthesis could be eradicated. In all five patients given 1,200 rads, a transient reduction in the de novo CNS IgG synthesis rate was noted. In ten patients given 1,800 rads, the following occurred: a reduction in synthesis rate in three patients, a reduction followed by enhancement in two, only enhancement in four, and no change in one. In all five additional patients, a therapy of adrenocorticotropic hormone (ACTH) followed by prednisone in combination with 1,800 rads produced greater and more persistent decreases in CNS IgG synthesis, but did not block the enhancement effect. Only two of 19 patients who had abnormal CNS IgG synthesis rates had reductions to normal; no patients showed changes in the number or pattern CSF IgG oligoclones. Hence, no treatment eradicated de novo CNS IgG synthesis. A persistent decrease in CSF leukocytes occurred in all 20 patients due to the reduction of small lymphocytes (not dose related). The blood-brain-barrier to albumin concentration was transiently damaged in 11 of 15 patients given irradiation, but when patients were premedicated with ACTH/prednisone therapy, no damage was found. None of the patients demonstrated neurological improvement, change in the activity of their disease, or persistent adverse effects. PMID- 6252877 TI - Immunoglobulin and complement deposits in nerves of patients with chronic relapsing polyneuropathy. AB - Sural nerve biopsy specimens from seven patients with chronic relapsing polyneuropathy (CRP) were studied by direct immunofluorescence. Granular deposits containing IgM (7/7) and C3 (6/7) (and occasionally IgG, 3/7) were found in intraneural blood vessels. Linear deposits of IgM (6/7) (and occasionally IgG, 3/7) without C3 (0/7) were found on the Schwann cell plasmalemma (and sometimes extending deeper into the Schwann cell) of yet undemyelinated portions of nerve fibers. Albumin and fibrinogen were not found in any locus. In sural nerves of ten disease-control patients with non-dysimmune chronic perpheral neuropathies, no deposits were seen on the vessels or the nerve fibers. The Schwann cell deposits may reflect a complement-independent IgM antibody toxic to Schwann cells that underlies the pathogenesis of CRP, perhaps facilitated in its passage across the blood-nerve barrier by damage from the complement-binding IgM complexes in the intraneural vessels. PMID- 6252878 TI - Uncommon causes of the lateral medullary syndrome. Report of a case of metastatic carcinoma. PMID- 6252879 TI - Bacterial collagenase. Proposed adjunct to vitrectomy with membranectomy. AB - Clostridiopeptidase A digested preretinal cicatricial tissue without causing morphological alteration of normal retina during a 30-minute incubation in the rabbit. Light and transmission electron microscopy were used to determine effects on the inner limiting membrane and retinal ganglion and Muller's cells and to evaluate enzyme digestion of preretinal scarring. Removal of the injected collangenase by vitrectomy resulted in normal electroretinograms and retinal morphology 48 hours postoperatively. If the enzyme was left in the eye for 24 hours, lens opacities, partial erosion of the inner limiting membrane, and extensive hemorrhage resulted. The specificity of action of the collagenase is due to the high degree of purity of the enzyme used and a substantial biochemical difference between scar collagen and basement membrane collagen. The injection of purified collagenase capable of digesting vitreal scar tissue while leaving the retina undamaged could represent a new approach to vitrectomy, specifically to facilitate certain cases of membranectomy. PMID- 6252880 TI - Malignant neoplasms of the external auditory canal and temporal bone. AB - In a review of 136 patients with squamous cell, basal cell, and salivary gland cancers involving the external auditory canal and temporal bone, the majority of patients had received prior treatment and came to us with recurrent tumor. Squamous cell carcinoma of the concha and cartilaginous ear canal behaved aggressively. Five-year survival in 35 patients with deep temporal bone involvement was 29%. The major reason for failure in this group was incomplete resection of disease. Postoperative irradiation was of no benefit when the cancer could not be completely excised. When compared with surgery alone, combined therapy with postoperative irradiation did improve local control in patients with completely resected lesions but did not demonstrate a corresponding increase in five-year survival. PMID- 6252881 TI - Fibre-optic bronchoscopy in small cell lung cancer: findings pre and post chemotherapy. AB - The aim of our study was to evaluate the role of fibre-optic bronchoscopy both in diagnosing patients with small cell lung cancer, and in assessing remission status following combination chemotherapy. Diagnostic bronchoscopic examination was performed in 40 patients and revealed that in all cases the lesion was located in the central bronchi. Following combination chemotherapy remission status in 18 patients was assessed by comparing the findings at repeat bronchoscopy with those of chest radiology. In ten patients there was no relationship between the findings at bronchoscopic examination and the chest radiograph (normal or abnormal). Adequate assessment of response of small cell lung cancer to therapy requires bronchoscopy in addition to chest radiology. PMID- 6252882 TI - Association of bovine viral diarrhoea-mucosal disease virus with ovaritis in cattle. PMID- 6252884 TI - Escherichia coli and rotavirus infections in four-week-old gnotobiotic piglets fed milk or dry food. AB - A haemolytic enteropathogenic E. coli (WG) and pig rotavirus were isolated from a field case of postweaning diarrhoea in pigs. Four-week-old gnotobiotic piglets fed on milk diet were found to be extremely susceptible to infection with WG E. coli. Piglets were less susceptible to the infection immediately after the diet was changed from milk to dry food, and were almost completely resistant 4 days after the change to dry food. There was no difference in the clinical response to infection with WG E. coli when the piglets were fed either a high energy diet or low energy diet. Four-week-old piglets fed milk showed mild symptoms of diarrhoea when inoculated with pig rotavirus. Symptoms were more severe when piglets were inoculated immediately after the change from milk to dry food. Piglets inoculated 4 days after the change of diet showed no symptoms of diarrhoea at all. Under the conditions of these experiments the enteropathogenic E. coli produced a more serious disease than did pig rotavirus. Infection of 4-week-old gnotobiotic piglets with both agents given sequentially produced a diarrhoeal disease that was more severe than that produced by each agent separately. PMID- 6252883 TI - Factors contributing to postweaning diarrhoea in a large intensive piggery. AB - Some aspects of postweaning diarrhoea (PWD) in a piggery during the first week after early weaning were investigated. A haemolytic enterotoxigenic strain of E. coli (O149:K88:H10) was regularly recovered from piglets with PWD while rotavirus was demonstrated on a number of occasions. Prior to weaning piglets were either free of, or shed very few, haemolytic E. coli in their faeces. However, all piglets were excreting haemolytic E. coli between 5 and 7 days after weaning. The role of rotavirus in PWD was unclear. There appeared to be a direct relationship between serum antibodies to rotavirus in the slow at farrowing and those of the piglets soon after birth. The decline of maternal neutralising antibody to rotavirus coincided with the immediate postweaning period (3 to 5 weeks after birth). This was followed by an increase in antibody levels, 5 to 8 weeks after birth. There was no significant difference in the growth rate between affected and unaffected piglets over a period of 120 days. Medication of water during the first week after weaning had no significant effect on the incidence of PWD in the herd. A change in both the weaner diet and the weaning procedure reduced piglet mortality associated with PWD by more than half. PMID- 6252885 TI - Transmission of a genital isolate of bovine herpesvirus 1 to calves by the respiratory route. PMID- 6252886 TI - In vitro biosynthesis and N-acetylation of beta-endorphin in pars intermedia of the rat pituitary. PMID- 6252887 TI - Primary effects of yeast killer toxin. PMID- 6252888 TI - Dephosphorylation and reactivation of phosphorylated pyruvate kinase by a cytosolic phosphoprotein phosphatase from human erythrocytes. PMID- 6252889 TI - Avermectin B1a: an irreversible activator of the gamma-aminobutyric acid benzodiazepine-chloride-ionophore receptor complex. PMID- 6252890 TI - Effects of vanadate on the cyclic AMP-protein kinase system in rat liver. PMID- 6252891 TI - Prereplicative modulation of nuclear protein kinases in the regenerating rat liver. PMID- 6252892 TI - On the feasibility of electron transfer to singlet oxygen from mitochondrial components. PMID- 6252893 TI - Removing bicarbonate/CO2 reduces the cGMP concentration of the vertebrate photoreceptor to the levels normally observed on illumination. PMID- 6252894 TI - Effects of alloxan-diabetes on the sodium-potassium adenosine triphosphatase enzyme system in dog hearts. PMID- 6252895 TI - Induction of choline kinase by polycyclic aromatic hydrocarbon carcinogens in rat liver. PMID- 6252896 TI - Diverse effects of Ca2+ on the prostacyclin and corticotropin modulation of adenosine 3': 5'-monophosphate and steroid production in normal cat and mouse tumor cells of the adrenal cortex. PMID- 6252897 TI - Kininases of human polymorphonuclear leucocytes. PMID- 6252898 TI - Stimulation of rat C6 glioma ecto-5'-nucleotidase by chronic ethanol treatment. PMID- 6252899 TI - Prostaglandin I2 receptors in a particulate fraction of platelets of various species. PMID- 6252900 TI - Interdependence of hemoglobin, catalase and the hexose monophosphate shunt in red blood cells exposed to oxidative agents. PMID- 6252901 TI - Inhibition of liver-microsome calcium pump by in vivo administration of CCl4, CHCl3 and 1,1-dichloroethylene (vinylidene chloride). PMID- 6252902 TI - Regulation of contraction by myosin phosphorylation. A comparison between smooth and skeletal muscles. PMID- 6252903 TI - Stimulation of the secretion of plasminogen activator from activated murine macrophages by microtubule disrupting agents and deuterium oxide. PMID- 6252904 TI - Interaction of drugs with a model membrane protein. Effects of four local anesthetics on cytochrome oxidase activity. PMID- 6252905 TI - Specific binding for opiate-like drugs in the placenta. PMID- 6252906 TI - Bone cell cultures as an experimental model. AB - The isolation and separation of bone cells with populations enriched for osteoclastic or osteoblastic phenotypes are described. Such systems offer the opportunity to compare and contrast the controls exerted by hormones, ions, and other agents on the functions of the individual bone cell types and may in the future provide explanation for the changes seen in bone tissue in various diseased states. PMID- 6252907 TI - Actions of calcitonin and mithramycin. PMID- 6252908 TI - Experimental basis for the clinical use of diphosphonates in Paget's disease of bone. PMID- 6252909 TI - Inhibition of adenine nucleotide translocase by oleoylcarnitine, oleoylcoa and oleate in isolated arterial mitochondria. AB - Adenine nucleotide translocase (AdNT) activity was studied in isolated mitochondria from normal rabbit aortas. The enzyme was inhibited by oleic acid, oleoylCoA, and oleoylcarnitine with 50% inhibition occurring at 5 muM, 6 muM and 14 muM, respectively (corresponding to 8, 10, and 23 nmol/mg protein). PalmitoylCoA and palmitoylcarnitine displayed similar potency to oleylCoA and oleoylcarnitine. The possibility that inhibition by fatty acid, acylCoA, and acylcarnitine could be attributed to non-specific detergency effects seems remote in that these compounds were more potent inhibitors of AdNT than equimolar concentrations of laurylsulfate. In addition, by use of the fluorescent probe N phenyl-1-naphthylamine, it was shown that under the experimental conditions, inhibition of AdNT occurred at concentrations not exceeding a critical micelle concentration (CMC). Specificity was also suggested in that octanoylCoA was a weak inhibitor of AdNT and acetylcarnitine, butyrylcarnitine, cholesteryl oleate, and sphingomyelin were not inhibitory to the enzyme. In contrast to the observed inhibition of arterial AdNT by oleoylCoA and oleoylcarnitine, AdNT in isolated rabbit and rat heart mitochondria was inhibited only by oleoylCoA. PMID- 6252910 TI - Possible relationship of cholesterol accumulation and collagen synthesis in rabbit aortic tissues. AB - Male adult New Zealand rabbits were fed a 2% cholesterol diet for 60 days followed by 10, 20, or 30 days of normal low cholesterol diet. Collagen synthesis was estimated by measuring aortic prolyl hydroxylase activity. Tissue cholesterol accumulation rates were estimated by dividing total tissue cholesterol by the number of experimental days. It was found there was a high degree of correlation between aortic collagen synthetic activity and the rate of aortic cholesterol accumulation. These data were interpreted as suggesting that increased collagen synthesis may be associated with the accumulation and/or retention of increased aortic cholesterol. PMID- 6252911 TI - Treatment of pituitary hyperfunction with proton beam irradiation: University Regional Hospital experience. PMID- 6252913 TI - Differential effects of myoneural blocking drugs on neuromuscular transmission. AB - The relationship between the depression in the amplitude of the compound muscle action potential and neuromuscular decrement (fade) was studied during the induction of non-depolarizing blockade, using a train of four supramaximal stimuli. Neuromuscular decrement (%) was defined as: [1 - (amplitude of fourth muscle action potential)/(amplitude of first muscle action potential)] x 100. When the amplitude of the first action potential was reduced by 50%, mean neuromuscular decrement increased in the order pancuronium < alcuronium < tubocurarine < frazadinium < gallamine. Similarly, the slope of the regression line relating the decrease in the amplitude of the action potential to decrement was least with pancuronium and greatest with gallamine. These results may reflect different affinities or intrinsic activities of the five drugs for prejunctional and postjunctional receptors. Thus, pancuronium may have a greater affinity for postsynaptic receptors, while tubocurarine and gallamine affect selectively the motor nerve terminal. It was confirmed that fazadinium had a more rapid onset on action than any of the other myoneural blocking drugs studied. PMID- 6252912 TI - Insulinoma: diagnosis and management. PMID- 6252914 TI - The eye as a mirror of systemic disease. PMID- 6252915 TI - Pharmacokinetics, beta-adrenoceptor blockade and anti-hypertensive action of labetalol during chronic oral treatment. AB - 1 beta-Adrenoceptor blockade, plasma labetalol concentrations and anti hypertensive actions were investigated at 2 hourly intervals during the interdose period of chronic oral therapy in six hypertensive patients. 2 beta-adrenoceptor blockade varied during the inter-dose period and was maximal 2 and 4 h after the oral dose (P < 0.05). 3 Systolic pressure rose during the interdose period (P < 0.05). A significant correlation was found between the degree of beta adrenoceptor blockade and the change in systolic pressure at 2 h after the oral dose. 4 Efficacy of labetalol as a beta-adrenoceptor antagonist and anti hypertensive drug was assessed 2 h after an oral dose during chronic eight hourly dosage in sixteen hypertensive patients. Pharmacokinetics of labetalol were studied in the same patients. 5 Peak plasma labetalol concentration occurred 2 h after the oral dose and subsequently the plasma concentration declined monoexponentially. 6 The steady state concentration (CSS) of labetalol was correlated significantly with the daily oral dose in mg kg-1, the mid point labetalol concentration (Cmax+Cmin) divided by 2 and the isoprenaline dose ratio 1 at 2 h after the oral dose. 7 No correlation was found between the antihypertensive effect and the CSS ng ml-1 labetalol or between the isoprenaline dose ratio-1 and the CSS labetalol ng ml-1. PMID- 6252916 TI - Mecillinam in patients on haemodialysis. PMID- 6252917 TI - The diagnostic value of circulating trophoblast-specific beta 1-glycoprotein (TSG) in cancer patients. PMID- 6252918 TI - A more general role for WR-2721 in cancer therapy. PMID- 6252919 TI - High-resolution proton nuclear magnetic resonance: application to the study of leukaemic lymphocytes. PMID- 6252920 TI - Bone metastases in childhood renal tumours. AB - Analysis of data from 1434 children with primary renal tumours revealed 57 who developed bone metastases. Of these, 54 were initially recorded as nephroblastoma. Fifty-two of the 57 cases were reviewed histologically, and only 18 were found to be Wilms' tumours. Twenty-three were classified as "Bone Metastasizing Renal Tumour of Childhood" (BMRTC), and a high male incidence was found for these tumours (M:F=6.7:1). Differences in the pattern of metastasis and the one-year survival between BMRTC and nephroblastoma are discussed. The rarity of bone metastases from true Wilms' tumours is emphasized. PMID- 6252921 TI - Silica-induced malignant histiocytic lymphoma: incidence linked with strain of rat and type of silica. AB - It has already been established that a single intrapleural inoculation of crystalline silica (quartz) produces malignant lymphomas of histiocytic type (MLHT) in Wistar-derived rats. It has now been shown that after treatment with Min-U-Sil, rats of the Alderley Park strain have a tumour incidence of 35%, whereas the incidence in Agus rats is 5% and in PVG 8%. There was also a significant difference in the incidence of MLHT caused by injecting different samples of crystalline silica, particularly of tridymite. There was correlation between cytotoxicity to mouse peritoneal macrophages and tumour incidence, except for one dust (DQ12). Zeta potential, number of particles and their size range were considered, but the incidence does not show a clear correlation with these measurements. The results are discussed. PMID- 6252922 TI - Treatments affecting the rate of asbestos-induced mesotheliomas. AB - 256 Wistar rats received a single injection into the right pleural cavity of UICC crocidolite in order to induce mesotheliomas. They were then given right intrapleural injectons of BCG, crystalline silica, talc, carrageenan or saline (as a control). There was no significant change in the mesothelioma rate in the rats exposed to BCG, silica or talc, but there was a 3-fold increase in mesothelioma incidence in the group injected with carrageenan. PMID- 6252923 TI - Immunization against primary, transplanted and spontaneous murine leukaemia using a live Moloney sarcoma virus vaccine. AB - The purpose of this study was to use an immunization protocol with Moloney sarcoma virus (MSV-M) as active immunogen against exogenous and endogenous leukaemia. The s.c. route was chosen since it offered advantages over the i.m. route: the primary sarcomas were smaller, the regression faster, there were fewer recurrences and there was good persistent immunity. Strong protection was obtained against primary leukaemias induced by Friend leukaemia virus (FLV), Moloney leukaemia virus (MLV), Rauscher leukaemia virus (RLV), Precerutti-Law leukaemia virus (PLLV/T2), and H179A leukaemia virus. It was not possible to protect against leukaemia induced by Gross leukaemia virus (GLV). With transplantable leukaemias the results varied: partial protection was observed against H110 leukaemia (induced with human material) and R14 leukaemia (induced by X-irradiation) whilst no protection was obtained against P277 leukaemia (induced by Moloney leukaemia virus). As for spontaneous leukaemias, immunized BALB/c mice showed an increased incidence over the controls, while in F1 (Swiss x AKR) mice the incidence was similar but the latent period was shorter. Furthermore, in long-term observations the MSV-M-immunized mice showed an increased mortaltiy, which could be related to (1) new phenotypic mixtures between MSV-M and leukaemia viruses; (2) reactivation of MSV-M sarcoma-genesis with age, and (3) genotype susceptibility to MSV-M. PMID- 6252924 TI - Effects of N-nitrosobis(2-oxopropyl)amine in newborn and suckling hamsters. PMID- 6252925 TI - Incidence of malignant disease in childhood: a 24-year review of the Manchester Children's Tumour Registry data. AB - The Manchester Children's Tumour Registry data for the period 1954-1977 have been analysed. The overall incidence of malignant disease in children aged 0-14 years in the north-west of England is estimated to be 100 per million person-years. The most common disease group is leukaemia, which forms about one third of the total number of cases. Among solid tumours, by far the most common presenting site is the central nervous system, representing nearly a quarter of all neoplasms. Wilms' tumour, neuroblastoma and soft-tissue sarcomas comprise approximately 5%, 6.5% and 6% respectively of the total. The tumours most frequently seen in adults (e.g. carcinoma of colon, lung and breast) are extremely rare in childhood. A significant excess of males was seen in acute lymphoid leukaemia, non-Hodgkin's lymphoma, Hodgkin's disease, medulloblastoma and hepatoblastoma. A female excess was found among germ-cell tumours. During the study period significant increases in incidence were seen among acute lymphoid leukaemia and epithelial tumours, and an increase in germ cell tumours approached significance. PMID- 6252926 TI - Collagenase immunolocalization studies of cutaneous secondary melanomas. AB - Immunoreactive collagenase has been demonstrated in 5/14 specimens of cutaneous secondary melanomas. In contrast, very little enzyme was seen in 10 specimens of normal human skin. All specimens were fixed within minutes of excision. These findings support the hypothesis that collagenase facilitates connective-tissue breakdown which is associated with tumour invasiveness and metastatic spread. PMID- 6252927 TI - Serum angiotensin-converting enzyme in malignant lymphomas, leukaemia and multiple myeloma. AB - Serum angiotensin-converting enzyme (SACE) was analysed in 27 patients with Hodgkin's disease, 25 with non-Hodgkin lymphoma, 14 with acute leukaemia, 15 with chronic leukaemia, and 15 with multiple myeloma. SACE was depressed in these patients as a whole, with a mean level of 19.9 mu/ml, compared with 116 healthy controls (mean 24.4 mu/ml, P < 0.001). This depression was greatest in chronic leukaemia and multiple myeloma. In Hodgkin's disease no relationship was found between enzyme activity and stage, activity, histopathology, treatment, mediastinal involvement or prognosis. In non-Hodgkin patients a poor prognosis was generally associated with low SACE activity. The low SACE activity was not related to recent corticosteroid treatment, and the cause and pathophysiological significance is unexplained. Since SACE is high in the granulomatous disorder sarcoidosis (which can mimic malignant lymphnode and blood diseases) SACE analysis can be valuable in evaluating patients with mediastinal lymphadenopathy and those in whom non-caseating epitheliod granulomas are found. PMID- 6252928 TI - ESR signals of lyophilized tissue. PMID- 6252929 TI - Hepatitis B surface antigen, hepatocellular carcinoma and cirrhosis in hong kong: a necropsy study: 1963-1976. AB - Hepatitis B surface antigen (HBsAg) was stained in liver tissue in 71% of 496 cases of cirrhosis with and without hepatocellular carcinoma (HCC) in Chinese coming to necropsy in Hong Kong from 1963-1976. Male cases numbered 417; HBsAg was positive in 83% of those in which HCC was combined with cirrhosis and in 62% of those with cirrhosis alone. Of 39 additional male cases of HCC without cirrhosis, 38% were HBsAg+. Similar proportions were recorded in the famale cases. This progression suggests a cumulative carcinogenic effect of persistent hepatitis B virus (HBV) fully expressed in the presence of cirrhosis. The approximate risk factors for males in Hong Kong who are HBsAg+ at the time of death, compared with HBsAg- males, are 6:1 for HCC alone, 16:1 for cirrhosis alone and 50:1 for HCC combined with cirrhosis. The frequency of HBsAg+ tests is much higher in Hong Kong than in the United Kingdom, and cirrhosis is calculated to be 2.8 times and HCC 11 times commoner. The high incidence of HCC in Hong Kong is not attributable solely to the high incidence of cirrhosis, but can be related to the high incidence of cirrhosis accompanied by persistent HBV. PMID- 6252930 TI - The therapeutic response of bronchial carcinoma xenografts: a direct patient xenograft comparison. AB - The chemotherapeutic response of a series of patients with bronchial carcinoma has been compared with the response of their xenografts established in immune suppressed CBA/lac mice. Xenograft response was assessed by the in situ endpoint of growth delay in subcutaneous tumours. Histology and chromosome analysis indicated that human characteristics were retained in the xenografts. 49 xenograft lines were attempted: 15/18 oat cell, 11/17 squamous, 6/8 large cell anaplastic and 6/6 adenocarcinomas were successfully established. 14 Lines (28%) were available (August 1979) for direct comparison of xenograft and donor patient response to the same chemotherapeutic agents. A positive correlation was found and provides support for the chemotherapeutic validity of xenografts. PMID- 6252932 TI - Pneumothorax associated with primary bronchial carcinoma. PMID- 6252931 TI - Analysis of clonogenic human brain tumour cells: preliminary results of tumour sensitivity testing with BCNU. AB - Biopsies from 6 patients with glioblastoma multiforme were disaggregated and single cells were treated in vitro with various concentrations of BCNU and plated for cell survival. One patient's cells were sensitive to BCNU in vitro; after a single dose of BCNU her brain scan reverted to normal and she was clinically well. Five tumours demonstrated resistance in vitro. Three of these tumours progressed during the first course of chemotherapy with a nitrosourea and the patients died at 2 1/2, 4 and 8 1/2 months after operation. Two patients who showed dramatic responses to radiation therapy were considered unchanged after the first course of nitrosourea therapy (although one demonstrated tumour enlargement on brain scan). The correlation of in vitro testing of tumour cell sensitivity with actual patient response is encouraging enough to warrant further work to determine whether such tests should weigh in decisions on patient therapy. PMID- 6252933 TI - Persistence of pneumonia virus of mice and Sendai virus in germ-free (nu/nu) mice. AB - The pathogenicity and persistence of pneumonia virus of mice (PVM) and Sendai virus has been studied using germ-free nu/nu mice. PVM was found to infect cells of the bronchial epithelium (and the alveolar wall) of the lungs of germ-free nu/nu mice using the immunoperoxidase technique. The virus was located in the bronchial epithelium for 11 days before elimination, but persisted in the alveolar wall for the duration of the experiment (20 days). After Day 10 a humoral antibody response to PVM was observed which persisted, although at a low level (1 in 40), by haemagglutination-inhibition (HI) testing. Sendai virus in nu/nu mice also infected cells of the bronchial epithelium and this persisted for the duration of the experiment (27 days). The persistence of virus in the bronchial epithelium in relation to lack of humoral antibody is discussed with reference to local secretory antibody production, especially since this does not occur with PVM. PMID- 6252934 TI - Experimental pigbel: the production and pathology of necrotizing enteritis due to Clostridium welchii type C in the guinea-pig. AB - An animal model for pigbel in man was developed using guinea-pigs. Intragastric dosing with growing cultures of Clostridium welchii Type C only produced necrotic lesions if protease inhibitors were given as well. beta toxin, which is made by the Type C organism, causes the intestinal damage and is very easily destroyed by proteases. Protease inhibitors in soybean and aprotinin were effectively in inducing disease in animals on a normal diet, while inhibitors in sweet potato, which inhibit only trypsin, were only effective in animals on a low-protein diet. In experiments using intragastric dosing, and in those where cultures and toxic filtrates were injected directly into the jejunum, the animals could be protected with an excess of pancreatic enzymes or by active or passive immunization against beta toxin. The pathology off Type C necrotizing enteritis in guinea-pigs had the macroscopic and microscopic features of pigbel in man. These experiments suggested the basic importance of a low-protein diet and dietary trypsin inhibitors in the pathogenesis of pigbel in man. PMID- 6252935 TI - The effect of mouse strain on the pathogenesis of the encephalitis and demyelination induced by avirulent Semliki Forest virus infections. AB - Mice from the following strains--Simpson, SWR/J, TO, CBA/Ca, CW (outbred), LAC/G (outbred), SJL/J and Swiss A2G (outbred)--were infected i.p. with avirulent Semliki Forest virus. Clinical signs of disease were noted, histopathological changes assessed and the blood and brain virus infectivities and serum immunoglobulin levels were measured. Only the CW, TO and Swiss/A2G animals showed convincing evidence of demyelination at the light microscopy level but all strains developed encephalitis and microcystic (spongiform) lesions. PMID- 6252936 TI - Histopathological changes in the lungs of influenza-infected mice superinfected with Staphylococcus aureus. AB - Histopathological changes in the lung were assessed in a model infection of mice using swine influenza virus and Staphylococcus aureus. Virus preinfection markedly enhanced both the persistence of S. aureus and the extent and duration of the inflammatory response. Lymphocytic infiltration was increased and regeneration and squamous metaplasia were delayed, suggesting an enhancement of an immunopathological response to the virus. Mice with the dual infection showed a decrease in phagocytic cell infiltration of the lung compared to that observed in those with the bacterial infection only, and this may reflect a decline in alveolar macrophage function after influenza infection. PMID- 6252937 TI - Effects of hydrocortisone on the adrenaline-adenylate cyclase system of the skin. AB - Using pig skin slices, we investigated the effects of hydrocortisone on the adenylate cyclase system of the skin. In short-term experiments, hydrocortisone, when added singly or in combination with other stimulators of adenylate cyclase in the skin (adrenaline or histamine), had no effect on cyclic AMP accumulation. However, when skin slices were incubated with hydrocortisone for more than 6 h, the response to adrenaline differed, with a greater accumulation of cyclic AMP in the hydrocortisone-treated skin. This effect was seen at a concentration of more than I micrometer hydrocortisone and was most marked 48 h later, while responses to adrenaline in control skin gradually decreased and remained low. Histamine, which is another stimulator of adenylate cyclase of the skin, did not cause a greater cyclic AMP accumulation in response to this hydrocortisone treatment. There was no significant difference in either low Km or high Km cyclic AMP phosphodiesterase activities as a result of this hydrocortisone treatment. Hydrocortisone seems to act by protecting the adrenaline-adenylate cyclase system of the skin. PMID- 6252938 TI - Heterozygote detection in Fabry's disease using mailed hair roots. PMID- 6252939 TI - Cyclic AMP is decreased in mononuclear leukocytes from psoriasis patients. PMID- 6252940 TI - Pagetoid reticulosis: a disease of histiocytic origin. AB - A patient with Pagetoid reticulosis has been investigated using standard transmission electron microscopy and an immunohistochemical technique for identifying T lymphocytes in situ in light and electron microscopy. Our results indicate that the majority of the cells in the underlying dermal infiltrate are T lymphocytes but that only very few T lymphocytes are found in the extensive epidermal infiltrate. Ultrastructurally the majority of the abnormal cells in the epidermis are of histiocytic origin. PMID- 6252941 TI - Electron microscope and high resolution autoradiographic studies of the erythroblasts in haemoglobin H disease. AB - Electron microscope studies of bone marrow from a patient with haemoglobin H (HbH) disease have revealed the presence of highly condensed branching intracytoplasmic inclusions within a proportion of the early and late polychromatic erythroblasts and reticulocytes. Intraerythroblastic inclusions of this type have not yet been described in any other haematological disorder and may well be a specific feature of HbH disease. Electron microscope autoradiographic studies of the marrow cells from the patient with HbH disease revealed that (1) active protein synthesis continues in inclusion-containing erythroblasts and (2) there is a rapid precipitation of a considerable proportion of the newly synthesized free beta chains onto the surfaces of preformed inclusions, presumably after conversion to HbH. These electron microscope and electron microscope autoradiographic findings are quite different from the findings previously reported in homozygous beta thalassaemia using the same techniques. PMID- 6252942 TI - Erythrocyte pyrimidine 5'-nucleotidase. AB - In this study 31 family members of a patient with erythrocyte pyrimidine 5' nucleotidase deficiency were studied. The activity of this enzyme in their erythrocytes is compared with levels in normal subjects and the problems surrounding heterozygote detection are discussed. The mean erythrocyte pyrimidine 5'-nucleotidase activity in 158 normal fresh blood samples was 130 +/- SD 29.8 mU/gHb. There was no significant difference between males and females. The enzyme level in a patient with non-spherocytic haemolytic anaemia was 6 mU/gHb. Of 31 relatives of the enzyme deficient patient examined five were clearly heterozygous for the enzyme defect. Their enzyme levels were below 50 mU/gHb. The father, who is an obligatory heterozygote, had an enzyme level of 87 mU/gHb which falls within the low values of the normal range. The distribution of enzyme activity in 26 family members having enzyme activities greater than 50 mU/gHb suggests that six of these may be carriers of the defective gene. We were unable to identify carriers by enzyme kinetic studies, electrophoresis, chromatographic examination of acid extractable nucleotides or measurement of enzyme levels in young and old erythrocyte populations. The last-mentioned technique showed that erythrocyte 5' nucleotidase activity in reticulocytes may be as high as 1785 mU/gHb and declines rapidly as the cell ages reaching about 50 mU/gHb in the oldest cells. Blood samples which had been stored frozen were examined to see whether such samples were satisfactory for population studies. The mean enzyme activity 151 blood samples stored frozen for more than 12 months was 153+/-SD 44.7 mU/gHb. The increase in enzyme levels in the frozen samples appears to be greatest in samples showing haemolysis. In spite of the increased enzyme level frozen samples could be used to detect subjects with enzyme deficiency and some heterozygotes. PMID- 6252943 TI - The red blood cell membrane in thalassaemia. PMID- 6252944 TI - The fluidity gradient in erythrocyte membranes in hereditary spherocytosis: a spin label study. AB - The fluidity gradient and sulphydryl groups in erythrocyte ghost membranes from healthy subjects and from seven patients with hereditary spherocytosis (HS) were studied by spin label techniques. The mobility of the stearic acid spin labels was lower in the spherocyte membranes, indicating greater stability of the phospholipid layer in these membranes than in those of matched controls. This stabilization was most distinct in the intermediate and deep membrane layers. No clear differences were observed in the protein sulphydryl groups. It is suggested that the decreased cellular deformability characterizing spherocytes reflects altered lipid organization or lipid-protein interaction in the interior of the cell membrane. PMID- 6252945 TI - Membrane characteristics and metabolic properties of glucose-6-phosphate dehydrogenase deficient red cells. AB - Two Finnish variants of reduced erythrocyte glucose-6-phosphate dehydrogenase (G 6-PD) activity were studied. The G-6-PD Espoo variant is characterized by severe enzyme deficiency which is normally non-haemolytic although primaquine sensitive. The other variant, G-6-PD Helsinki, in which the enzyme activity is moderately reduced, is associated with chronic haemolytic anaemia. The activity of the pentose phosphate pathway was not stimulated by methylene blue in G-6-PD Espoo cells, whereas in normal and G-6-PD Helsinki cells there were increases in shunt activity of 64.5- and 5.3-fold, respectively. As judged by the accumulation of 6 phosphogluconate after incubation with 6-aminonicotinamide, the activity of the pentose phosphate pathway was similar in normal and G-6-PD Helsinki cells, whereas in G-6-PD Espoo cells the metabolic flux through this pathway was decreased. Quantities of sulphydryl groups in intact cells and isolated membranes were similar in normal and G-6-PD deficient cells, as revealed by spin label experiments. In contrast to the situation in normal cells, sulphydryl groups in G 6-PD Espoo cells, and to a lesser extent in G-6-PD Helsinki cells, were sensitive to oxidation by acetylphenylhydrazine. In the G-6-PD Helsinki cells, but not in the G-6-PD Espoo cells, membrane fluidity was increased, as judged from the increased mobility of the stearic acid spin label. Mechanisms are discussed by which G-6-PD deficient cells retain adequate levels of NADPH during resting conditions, and it is suggested that the chronic haemolysis associated with G-6 PD Helsinki could be due to a defect in the lipid region of the cell membrane. PMID- 6252946 TI - Effect of kidney damage on the mobilisation of mercury by thiol-complexing agents. PMID- 6252947 TI - A prospective study of primary cytomegalovirus infection in pregnant women. AB - During a four year study, sera were obtained from 5575 women attending for antenatal care and 3188 (57.2 per cent) were shown to possess complement fixing antibodies to cytomegalovirus (CMV). A total of 1608 seronegative women were followed to term and 14 (0.87 per cent) primary CMV infections occurred in either the second or third trimester. Transplacental spread of CMV occurred in 3 out of 12 (25 per cent) of the 14 babies born to infected mothers. All 14 babies were apparently normal at birth but short term clinical follow-up has already revealed that one child has impaired hearing whilst another is microcephalic. The women were also monitored serologically throughout pregnancy for evidence of rubella infections. Only 12 infections were detected and 7 of these occurred during the large rubella epidemic of 1978. Of the 10 pregnancies which were allowed to proceed to term, transplacental spread of rubella virus occurred in 1 out of 7 (14 per cent). During this study period, CMV infections occurred as frequently as did rubella infections. We therefore conclude that, apart from those years when extensive epidemics occur, many more pregnant women are infected with CMV than with rubella virus. PMID- 6252948 TI - The effect of various regimens of hormone therapy on serum cholesterol and triglyceride concentrations in postmenopausal women. AB - The serum cholesterol and triglyceride concentrations of 84 postmenopausal women both before and after 2, 6 and 12 months therapy with various regimens of hormone therapy were measured. There was little alteration in mean serum cholesterol concentration with cyclical oestrogens but both sequential mestranol and norethisterone and sequential oestradiol valerate and norgestrel significantly reduced the mean serum cholesterol concentration to a level similar to that found in age-matched premenopausal women. There was a small and sometimes significant rise in serum triglyceride concentration with cyclical oestrogens. Sequential mestranol and norethisterone significantly elevated serum triglyceride levels, but sequential oestradiol valerate and norgestrel significantly depressed them. The results suggest that the progestogenic agent norgestrel has an important role to play in reducing both serum cholesterol and triglyceride levels, and that the sequential preparations, by virtue of their greater cholesterol lowering effect, should perhaps be preferred to cyclical oestrogens. PMID- 6252949 TI - Glaucoma in a case of Hurler disease. AB - The electron microscopic appearances of the corneoscleral and iris tissue removed at operation from a child with Hurler disease and glaucoma showed distinctive swollen cells with intracellular inclusions similar to those which are observed in other tissues in these patients and which are due to abnormal lysosomal storages of mucopolysaccharides. Some recent observations on the possible relationship between mucopolysaccharides and the drainage of fluid from the anterior chamber are briefly reviewed and correlated with the present observations. The development of glaucoma in this patient is thought to be associated with the presence of the mucopolysaccharide-containing cells in the region of the aqueous drainage channels. PMID- 6252950 TI - An outbreak of adenovirus type 4 conjunctivitis. AB - An unusually large outbreak of conjunctivitis caused by adenovirus type 4 involved 113 proved cases during a 7-month period. Though the disease was less severe than is commonly seen in epidemic keratoconjunctivitis caused by other serotypes, the cornea was affected in 23% of cases and symptoms persisted for at least 5 weeks in 6 patients. A concurrent increase in nonocular adenovirus type 4 infections in the Bristol area was not observed. Nine of the cases could have arisen as a result of hospital cross-infection. PMID- 6252951 TI - The effects of diet on some metabolic enzymes in the small intestinal mucosa during lactation in the rat. PMID- 6252952 TI - Effects of pyrophosphate, triphosphate, and potassium chloride on adenylate deaminase from rat muscle. AB - Inorganic pyrophosphate and triphosphate inhibit adenylate deaminase from rat skeletal muscle with K1 values of 10 and 1.5 microM, respectively, in the presence of 150 mM KCl at pH 7. They act by reducing the apparent affinity of the enzyme for AMP, with relatively small effects on Vmax. The inhibitions are diminished by H+, the KI values increasing two- to threefold in going from pH 7.0 to 6.2, and are relieved by ADP. These properties are similar to the inhibitions produced by GTP and ATP, indicating that pyrophosphate and triphosphate act like analogues of the nucleoside triphosphates. Neither of these inhibitors shows relief of inhibition at high concentrations as do ATP and GTP. These results suggest that nucleotides interact with the inhibitor site of the enzyme primarily through their phosphate moieties and with the activator site primarily through their nucleoside moieties. As the concentration of KCl is increased from 25 to 300 mM, the apparent affinities of the enzyme for ATP, GTP, orthophosphate, pyrophosphate, and triphosphate are decreased 8-100-fold. The cooperativity of the inhibitions is increased with the Hill coefficient rising from 1.0 to 1.3 1.8, and the maximum inhibition approaches 100%. Maximum activation by ADP is reduced from 1800% at 25 mM KCl to 80% at 200 mM KCl. Experiments with (CH3)4NCl indicate that activation of the enzyme by KCl involves both specific K+ effects and ionic strength effects. PMID- 6252953 TI - Amino acid sequence of a collagenolytic protease from the hepatopancreas of the fiddler crab, Uca pugilator. AB - The amino acid sequence of a collagenolytic protease from the hepatopancreas of the fiddler crab, Uca pugilator, was determined from the structures of overlapping tryptic, chymotryptic, thermolytic, staphylococcal protease, and cyanogen bromide peptides together with automated sequencer analysis of the intact protein. Crab collagenase is a serine protease composed of 226 residues which is capable of degrading the native triple helix of collagen under physiological conditions. When aligned for optimal homology, crab collagenase displays 35% identity with bovine trypsin, 38% with bovine chymotrypsin B, and 32% with porcine elastase. The six half-cystinyl residues in crab collagenase correspond to those forming three of the five disulfide bonds in chymotrypsin. The residues forming the charge relay system of the active site of chymotrypsin (His-57, Asp-102, and Ser-195) are found in corresponding regions in crab collagenase, and the sequences around these residues are well conserved. The primary structure of crab collagenase is the first reported for a serine protease from crustacean hepatopancreas and the first reported for a serine protease possessing the unusual property of being able to degrade native helical collagen. PMID- 6252954 TI - Physical studies of the interaction of a calf thymus helix-destablizing protein with nucleic acids. AB - UP1, a calf thymus protein that destabilizes both DNA and RNA helices, dramatically accelerates the conversion of the inactive conformers of several small RNA molecules to their biologically active forms [Karpel, R. L., Swistel, D. G., Miller, N. S., Geroch, M. E., Lu, C., & Fresco, J. R. (1974) Brookhaven Symp. Biol. 26, 165-174]. Using circular dichroic and spectrophotometric methods, we have studied the interaction of this protein with a variety of synthetic polynucleotides and yeast tRNA3Leu. As judged by perturbations in polynucleotide ellipticity or ultraviolet absorbance, the secondary structures of the single stranded helices poly(A) and poly(C), as well as the double-stranded helices poly[d(A-T)] and poly(U.U), are largely destroyed upon interaction with UP1 at low ionic strength. This effect can be reversed by an increase in [Na+]: half the UP1-induced perturbation of the poly(A) CD spectrum is removed at 0.05 M Na+. The variation of poly(A) ellipticity and ultraviolet absorbance with [UP1]/[poly(A)]p is used to determine the length of single-stranded polynucleotide chain covered by the protein: 7 +/- 1 residues. A model is presented in which the specificity of UP1 for single strands and their concomitant distortion are a consequence of maximal binding of nucleic acid phosphates to a unique matrix of basic residues on the protein. Analogous to the effect on polynucleotides, UP1-facilitated renaturation of yeast tRNA3Leu follows the partial destruction of the inactive tRNA's secondary structure. At the tRNA absorbance maximum, UP1 effects a hyperchromic change of 10%, representing one-third of the secondary structure of the inactive conformer. This change is also clearly observable as a perturbation of the tRNA's circular dichroism spectrum. PMID- 6252955 TI - Preparation of a decadeoxyribonucleotide helix for studies by nuclear magnetic resonance. AB - A self-complementary decadeoxyribonucleotide d-CpCpApApGpCpTpTpGpG was chemically synthesized by a procedure based on the phosphotriester approach. This procedure was carefully monitored and appropriately modified to ensure the purity of oligomer components at each step of the synthetic scheme. Extensive use was made of both analytical and preparative high-pressure liquid chromatography to purify and characterize the decamer and its constituent oligonucleotides. The final product (1318 A257 units or 16.5 mumol) was obtained in high purity and sufficient quantity for extensive physical studies by UV, CD, and NMR spectroscopy. Our preliminary results show that at a strand concentration of 1.3 X 10(-5) M and in 0.10 M sodium chloride and 0.01 M sodium phosphate buffer, pH 7.0, the decamer duplex has a Tm at 47 degrees C. The CD spectrum of this decamer duplex is similar to that of B-form DNA. All the resonances of the nonexchangeable base protons of the decamer are well resolved in the 1H NMR spectrum, when the single-stranded form was examined by using a 360-MHz spectrometer and when the duplex form was examined by using a 600-MHz spectrometer. These base proton resonances have been tentatively assigned by using the incremental assignment technique. Although the decamer duplex serves as a substrate for AluI restriction endonuclease, it is not cleaved by HindIII endonuclease. PMID- 6252956 TI - Inhibition of ion permeability control properties of acetylcholine receptor from Torpedo californica by long-chain fatty acids. AB - The characteristics of fatty acid inhibition of acetylcholine receptor function were examined in membrane vesicles prepared from Torpedo californica electroplax. Inhibition of the carbamylcholine-induced increase in sodium ion permeability was correlated with the bulk melting point of exogenously incorporated fatty acids. Above its melting temperature, a fatty acid could inhibit the large increase in cation permeability normally elicited by agonist binding to receptor. Below its melting temperature, a fatty acid was ineffective. None of the fatty acids altered any of the ligand binding properties of the receptor. Inhibitory fatty acids did not induce changes in membrane fluidity, as determined by electron paramagnetic resonance using spin-labeled fatty acids. The spin-labeled fatty acids also acted as inhibitors, and the extent of inhibition depended largely on the position of the nitroxide group along the fatty acid chain. Addition of noninhibitory fatty acid to the vesicle membranes did not protect the receptor from inhibition by spin-labeled fatty acids. The effects of free fatty acids on acetylcholine receptor function are attributed to the disruptions of protein lipid interactions. PMID- 6252957 TI - Electron transfer reactions of high-potential iron-sulfur proteins and c-type cytochromes. AB - Studies of electron transfer by biological oxidation-reduction proteins frequently focus on the interaction of a particular protein with nonphysiological oxidants and/or reductants. This approach, although valuable, is limited by the size and chemistry of the nonphysiological reactants. To further the understanding of biological electron transfer, we have investigated the interaction of two examples of high-potential iron-sulfur proteins (HIPIP's) with mitochondrial cytochrome c (horse heart) and bacterial cytochrome c2 from Rhodospirillum rubrum, Rhodopseudomonas palustris, Rhodopseudomonas capsulata, and Rhodopseudomonas sphaeroides. On the basis of the kinetics of electron transfer between the various HIPIP's and cytochromes, it appears that the interactions are more complex than those observed with nonphysiological reactants. We conclude that (1) specific sites on both the HIPIP's and the cytochromes mediate electron transfer with the effect of ionic strength different from that expected on the basis of the interaction of the various proteins with iron hexacyanides, (2) the interaction of HIPIP with some of the cytochromes investigated is heterogeneous, resulting from at least two possible orientations (cytochrome dependent) for interaction leading to electron transfer, and (3) no long-lived complexes between the HIPIP's and cytochromes are formed due to rapid equilibrium between the two proteins. This last conclusion suggests that the measured second-order rate constant is in fact the product of the association constant (for any HIPIP and a particular cytochrome) and a first-order rate constant reflecting the rate-limiting step leading to products. PMID- 6252958 TI - Apurinic/apyrimidinic endonuclease sensitive sites as intermediates in the in vitro degradation of deoxyribonucleic acid by neocarzinostatin. AB - Neocarzinostatin (NCS) induces alkali-labile sites in DNA which are stabilized by NaBH4 reduction. The stabilized sites are sensitive to an AP endonuclease from human lymphoma cells. NCS-induced degradation of supercoiled Col E1 DNA proceeds in stepwise fashion with apurinic/apyrimidinic (AP) sites as intermediates. Degradation is increased when reaction occurs in the presence of AP endonuclease, and DNA reacted with NCS can be shown to have numerous AP endonuclease sensitive sites. PMID- 6252959 TI - Repair of neocarzinostatin-induced deoxyribonucleic acid damage in human lymphoblastoid cells: possible involvement of apurinic/apyrimidinic sites as intermediates. AB - Neocarzinostatin (NCS) induces repair in a xeroderma pigmentosum lymphoblastoid line deficient in the ability to repair DNA damage induced with (acetoxyacetyl amino)fluorene. Repair was demonstrated by the induction of repair synthesis and by the disappearance of NCS-induced single-strand breaks and/or alkaline-labile sites in DNA. Estimation of NCS-induced repair patch size, based on the density shift induced in DNA by extensive shear after incubation of treated cells in medium with bromodeoxyuridine or by calculation from the extent of restoration of DNA sedimentation profiles in alkaline sucrose gradients and the amount of repair synthesis measured by the BND cellulose method, indicated that only a few nucleotides were inserted per repaired region. NCS-treated bacteriophage T7 DNA requires incubation with alkaline phosphatase to make it a substrate for DNA polymerase I. NCS-reacted T7 DNA, even after phosphatase treatment, is not a substrate for a DNA polymerase alpha obtained from human lymphoma cells. NCS treated T7 DNA did serve as a substrate for the DNA polymerase alpha when incubated with an apurinic/apyrimidinic (AP) endonuclease with associated 5'-3' exonuclease activity. The results suggest that NCS-induced AP sites could be intermediates for the in vivo repair synthesis. PMID- 6252960 TI - Binding of Clostridium perfringens [125I]enterotoxin to rabbit intestinal cells. AB - 125I-Labeled enterotoxin from Clostridium perfringens was utilized to characterize the association of the enterotoxin with cells isolated from rabbit intestine and tissue homogenates from liver, kidney, and brain. The enterotoxin was found to bind in a specific and saturable manner to cells from intestine and to tissue homogenates from liver and kidney but not the brain. Detailed studies of the binding were carried out with the ileal epithelial intestinal cells. The rate and amount of binding of enterotoxin to cells appeared to be temperature dependent. Apparent affinity and association and dissociation rate constants were calculated for what appeared to be two classes of saturable binding sites. The amount of enterotoxin molecules that bound per milligram of cell protein was similar in tissue of intestinal, liver, and kidney origin (approximately 10(13) molecules/mg of cell protein). Spontaneous dissociation into the supernatant medium was observed to be much slower than expected from calculations based on the rate of association. Chaotropic ions did not enhance dissociation of the enterotoxin from cells. Enterotoxin binding was demonstrated to be heat labile (binding ability was lost after the enterotoxin was heated for 10 min at 60 degrees C). A mechanism is described whereby the enterotoxin binds and then is inserted into the membrane where it becomes trapped. PMID- 6252961 TI - Coupling between reduced nicotinamide adenine dinucleotide oxidation and metabolite transport in renal brush border membrane vesicles. AB - In a previous communication [Gimenez-Gallego, G., Benavides, J., Garcia, M.L., & Valdivieso, F. (1980) Biochemistry (preceding paper in this issue)] we have reported the occurrence of a NADH oxidase activity in the renal brush border membranes. The brush border membranes can utilize the energy from the oxidation of NADH to drive the transport of amino acids (aspartic and glutamic acids), organic acids, and the lipophilic cation tetraphenylphosphonium (TPP). The coupling between NADH oxidation seems to be due to the formation of a proton electrochemical gradient (delta-mu H+) as indicated by the effect of specific ionophores. This system may be implicated in the reabsorption process in the renal tubules and in the maintenance of the delta-mu H+ (positive and acidic in the luminal side) previously described in the renal tubules "in vivo". PMID- 6252962 TI - Redox and spectroscopic properties of oxidized MoFe protein from Azotobacter vinelandii. AB - The MoFe protein from Azotobacter vinelandii undergoes a six-electron oxidation by various organic dye oxidants with full retention of initial activity. Reduction of the oxidized protein by S2O42- and by controlled potential electrolysis indicates the presence of two reduction regions at -290 and -480 mV, each requiring three electrons for complete reaction. Control of the oxidation conditions provides a means for preparing two distinct MoFe protein species selectively oxidized by three electrons. Selective reduction of the redox region at -290 mV causes development of the EPR signal associated with fully reduced MoFe protein while reduction at -480 mV produces a change in the visible spectrum but has no effect on the EPR signal intensity. Kinetic differences for reduction of the two redox regions indicate that the cofactor region undergoes a more rapid reaction with reductant than the other metal redox sites. PMID- 6252963 TI - The effect of pH and ionic strength on the steady-state activity of isolated cytochrome C oxidase. AB - 1. The turnover number and apparent Km of isolated beef-heart cytochrome c oxidase were found to increase continuously when the pH was lowered from 8.6 to 4.6 (turnover number 32-630 s-1). In this pH range neither irreversible denaturation of the enzyme nor an optimum for the turnover number was observed. 2. The turnover number of cytochrome c oxidase was found to be independent of ionic strength. It was concluded that the dependence of the activity of cytochrome c oxidase on ionic strength is caused by a change in the value of Km for cytochrome c. 3. The pH dependence of the turnover number of cytochrome c oxidase can be described by a simple model in which at least three sites on the complex of cytochrome c oxidase with cytochrome c (pKa 8.0, 6.5 and 4.8) can take up a proton. PMID- 6252965 TI - Membrane adenosine triphosphatase activities in rat pancreas. AB - The membrane ATPase activities present in rat pancreas were studied to investigate the possible role of ATPase enzymes in HCO3(-) secretion in the pancreas. It was found that all the HCO3(-)-sensitive (anion-sensitive) ATPase activity was accountable as pancreatic mitochondrial ATPase, thus supporting the view that a distinct plasma membrane 'bicarbonate-ATPase' is not involved in HCO3(-) secretion in pancreas. A remarkably high Mg+- and CA2+-requiring ATPase activity (30 mumol ATP hydrolysed/min per mg) was found in the plasma membrane fraction (rho = 1.10-1.13). This activity has been characterized in some detail. It is inhibited by p-fluorosulfonylbenzoyladenosine, an affinity label analogue of ATP and the analogue appears to label covalently a protein of Mr approximately 35 000. The (Ca2+ + Mg2+)-ATPase activity did not form a 'phosphorylated intermediate' and was vanadate-insensitive. These and other tests have served to demonstrate that the (Ca2+ + Mg2+)-ATPase activity is different in properties from (Na+ + K+)-ATPase, Ca2+-ATPase, (H+ + K+)-ATPase or mitochondrial H+-ATPase. Apart from the (Ca2+ + Mg2+)-ATPase of plasma membrane and mitochondrial ATPase, the only other membrane ATPase activities noted were (Na+ + K+)-ATPase, which occurred in the same fractions as the (Ca2+ + Mg2+)-AtPase at rho = 1.10-1.13 and was of surprisingly low activity, and an ATPase activity in light membrane fractions (rho - 1.08-1.09) derived from zymogen granule membranes. At this time, therefore, there is no obvious candidate for an ATPase activity at the luminal surface of pancreatic cells which is directly involved in ion transport, but the results presented here direct attention to the high activity (Ca2+ + Mg2+)-ATPase in the plasma membrane fraction. PMID- 6252964 TI - Inhibition of ionic transport and ATPase activities by serotonin analogues in the isolated toad lens. AB - The effects of serotonin and five other indoles were tested on the electrical parameters and ionic transport in the isolated toad lens. Serotonin, tryptophan and 5-hydroxy-L-tryptophan did not affect the electrical parameters of the lens at concentrations as high as 1 mM. Tryptamine, 5-methyltryptamine and 5 methoxytryptamine had dual effects: 1 mM in the posterior bathing solution depressed the potential difference of the posterior face of the lens, which resulted in an increase in the translenticular potential difference and short circuit current; 1 mM in the anterior solution (in contact with the lens epithelium) produced a quick and pronounced reduction of the potential difference of the anterior face. This resulted in a 90-100% decline of the translenticular short-circuit current. Serotonin and tryptamine were then tested for their effect on the ATPases of lens epithelium. Both amines inhibited the enzymes with tryptamine at 5 mM completely inhibiting all ATPase activity. Since tryptophan is transported from the aqueous humor into the lens and may be converted by lens enzymes to serotonin and tryptamine, these findings may have physiological implications in cataractogenesis. PMID- 6252966 TI - Kinetic analysis of simultaneously occurring proton-sorbose symport and passive sorbose transport in Saccharomyces fragilis. AB - Sorbose transport in Saccharomyces fragilis takes place both via an active sugar H+ symport system and via facilitated diffusion. To establish whether the two modes of transport proceed via the same transporter or via two different carriers, the kinetic consequences of both models were investigated. The kinetic equations for initial transport were derived for three possible reaction sequences with respect to sugar and H+ binding to the symport carrier: random binding and obligatory ordered binding with either sugar or H+ binding first, yielding six sets of kinetic parameters. Analysis of experimental data of sorbose transport in S. fragilis showed the existence of separate carriers for active, sorbose-H+ symport and facilitated diffusion. Furthermore, it could be concluded that the symport carrier shows random binding of sugar and H+. In recent literature, a similar combination of active and passive sugar transport in Rhodotorula gracilis and Chlorella vulgaris was interpreted as two modes of action of the same carrier, viz., active symport via the protonated, and facilitated diffusion via the unprotonated carrier. Analysis of the experimental data according to the criteria presented in this paper showed, however, that this supposition is untenable and that two different carriers must also be involved in these micro-organisms. PMID- 6252967 TI - The relationship between the transport of glucose and cations across cell membranes in isolated tissues. X. Effect of glucose transport stimuli on the efflux of isotopically labelled calcium and 3-O-methylglucose from soleus muscles and epididymal fat pads of the rat. AB - (1) The relationship between Ca2+ and sugar transport has been studied by comparing the washout of 45Ca and 3-O-[14C]methylglucose from preloaded isolated rat soleus muscles and whole epididymal fat pads. (2) In soleus muscle, nine different agents with well established stimulating effects on glucose transport were all found to produce a marked increase in 3-O-[14C]methylglucose washout, which in each instance was preceded by or coincided with a rise in the washout of 45Ca. (3) Trypsin, 2,4-dinitrophenol, p-chloromercuriphenylsulfonic acid, H2O2 and hyperosmolarity all produced dose-dependent stimulation of the washout of 45Ca and 3-O-[3H]methylglucose. Regression analysis showed a highly significant correlation between the increases in the two parameters (P < 0.001). (4) Depolarization and Na+ influx induced by veratrine were found to be associated with a marked rise in 45Ca release followed by stimulation of 3-O [14C]methylglucose washout. (5) In epididymal fat pads, six different agents known to stimulate glucose transport were found to produce a highly significant (P < 0.001) increase in the washout of 45Ca and 3-O-[14C]methylglucose. (6) It is concluded that in the major targets for insulin action, activation of the glucose transport system can be elicited by a rise in cytoplasmic Ca2+ concentration brought about by mobilization of Ca2+ from endogenous cellular pools. PMID- 6252968 TI - Active calcium transport in human red cells. PMID- 6252969 TI - Intracellular phospholipases A. PMID- 6252970 TI - Characterization and partial purification of dihydroxyacetone kinase in Dunaliella salina. AB - Dihydroxyacetone kinase from Dunaliella salina is stabilized against inactivation by maintainance in the presence of 2 M glycerol. In the stabilized form a two step purification procedure resulted in an enzyme preparation of about 440-fold purity which gave three bands (78 000--100 000 daltons) in the absence of denaturing agents on a polyacrylamide gel. The enzyme is specific for dihydroxyacetone and Mg2+-ATP complex as its substrates. It has sharp pH activity curve with pH optimum around 7.5 and little activity below 6. It is suggested that dihydroxyacetone kinase plays a central role in the mechanism of osmoregulation via glycerol in Dunaliella. PMID- 6252971 TI - Inactivation of Escherichia coli acetate kinase by N-ethylmaleimide. Protection by substrates and products. AB - Acetate kinase (ATP:acetate phosphotransferase, EC 2.7.2.1) from Escherichia coli exhibited a time-dependent loss of activity when incubated with N-ethylmaleimide at micromolar concentrations. However, prolonged incubation did not eliminate all catalytic activity and generally about 15% of its initial activity remained. When incubated with 7.2 microM N-ethylmaleimide, acetate kinase was inactivated with a rate constant of 0.063 min-1. Adenine nucleotides, ATP, ADP and AMP, protected the enzyme against such inactivation, but acetate up to 3.0 M and in the presence of 0.2 M MgCl2 and acetyl phosphate at 24 mM did not interfere with the rate of inactivation. While both acetate and acetyl phosphate did not affect the protection rendered by AMP, the presence of acetyl phosphate altered ADP protection. However, both substrates prevented ATP from protecting the enzyme. These data suggest that the binding sites for acetate and acetyl phosphate are different from that of the adenosine binding domain, but are in close vicinity to the phosphoryl binding regions of the nucleotides. PMID- 6252972 TI - A latent collagenase from rheumatoid synovial fluid. Purification and partial characterization. AB - 1. A latent collagenase (EC 3.4.24.3) has been isolated from rheumatoid synovial fluids and purified by (NH4)2SO4 precipitation and column chromatography, utilising Sephadex G-150, DEAE Sephadex A-50 and Sephadex G-100 superfine grade. 2. The final preparation activated by trypsin (EC 3.4.21.4) had a specific activity against thermally reconstituted collagen fibrils of 259 micrograms collagen degraded/min per mg enzyme protein, representing a nearly 800-fold increase over that of the original rheumatoid synovial fluid. 3. The latent collagenase preparation can be activated by trypsin and to some extent by HgCl2 but not by 3 M NaSCN, 3.5 M NaCl, 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) or p-chloromercuribenzoate. 4. Inhibition studies and the acrylamide gel electrophoretic pattern of collagen degradation products showed that the trypsin activated enzyme has the essential features of a neutral collagenase. 5. The molecular weights, determined by calibrated gel filtration, were 52 000 and 43 000 for the latent and the activated enzyme, respectively. 6. The nature of the latency of synovial fluid collagenase is discussed. PMID- 6252973 TI - The rapid purification of a phosphotransferase from wheat shoots. AB - A phosphotransferase from wheat shoots which specifically phosphorylates the 5' position of nucleosides has been purified by a simple procedure involving chromatography on Matrex Gel Blue A. PMID- 6252974 TI - Sulfite oxidase from Merluccius productus. AB - Sulfite oxidase (sulfite:oxygen oxidoreductase, EC 1.8.3.1) was purified 482-fold from liver of the Pacific hake Merluccius productus. The molecular weight of the enzyme was found to be 120 000 by gel exclusion chromatography on Sephadex G-100. Electrophoretic analysis on sodium dodecyl sulfate (SDS)-polyacrylamide gel revealed that the enzyme was composed of two subunits whose molecular weight was estimated to be 60 000. The pH optimum of the enzyme was 8.7; Ks for sulfite, 2.5 x 10(-5) M; and that for cytochrome c, 3.6 x 10(-7) M. The enzyme elicited an EPR signal at g = 1.97 characteristic of pentavalent molybdenum. Colorimetric analysis also disclosed that the enzyme contained 2 mol each of heme and molybdenum per mol of protein. This fish liver homogenate in isotonic sucrose solution was fractionated by differential centrifugation into nuclei, mitochondria, microsomes and supernatant (100 000 X g). The major portion of sulfite oxidase activity was found in mitochondria. The sulfite oxidase activity was markedly high in liver and kidney, as compared with that in heart, spleen, muscle, gill and eye. PMID- 6252975 TI - [Nature and mechanism of action of the solanidine glycosides solanine and chaconine on biological objects]. PMID- 6252976 TI - [Nature of a virus-specific protein detected in the composition of a ribonucleoprotein containing cellular messenger RNA during viral infection]. PMID- 6252977 TI - [Cardiotropic action of green toad venom (Bufo viridis Laur.)]. PMID- 6252978 TI - Biochemical aspects of DNA replication with particular reference to plants. PMID- 6252979 TI - Fragmentation pathways in electron impact mass spectra of methoxyhalobiphenyls. AB - The electron impact mass spectra of various methoxyhalobiphenyls have been reinvestigated. Previous findings, concerning the effect of the methoxy group upon the main fragmentation routes, have been confirmed and extended. In addition, studies of unimolecular and collision induced fragmentation of ions, using linked scan techniques, have been made. Such an approach permits the identification of substances with a minimal chromatographic separation prior to mass spectrometry. It has also led to some clarification of the fragmentation pathways leading to the observed cracking patterns. PMID- 6252980 TI - Method for analysis of polybrominated biphenyls by gas chromatography mass spectrometry. AB - Gas chromatography using a short packed column (45 cm, 0.2 cm i.d., 2% OV-101 on Gas-Chrom Q) with mass spectrometric detection in the selected ion monitoring mode has been found satisfactory for the analysis of lower as well as higher polybrominated biphenyls. Acceptable sensitivity (< 1 ng) may be achieved for this method by focusing selectively at either the low (m/z 20-600) or the high m/z 600-1000) range of the quadrupole filter (low range for mono- through hexabromobiphenyl, high range for hexa- through decabromobiphenyl). A tuning technique has been developed for low range and high range polybrominated biphenyls using the ion abundances of perfluorotributylamine as a standard. Standard ions for the quantitation of mono- through decabromo-biphenyls were selected and validated. The technique was applied to the analysis of a variety of environmental samples. PMID- 6252981 TI - New genetic approaches to industrially important fungi. PMID- 6252982 TI - [Relationship between the tonus of the walls of the internal carotid artery and cyclic adenylmonophosphate]. AB - Experiments were carried out in dogs with the use of resistography of circulatory isolated internal carotid artery. Both activation of adenyl cyclase by adenosine and inhibition of phosphodiesterase by theophylline in the vascular wall result in a significant decrease in the vasoconstrictor effect of prestaglandin E2. On the contrary, inhibition of adenyl cyclase by the beta-blocker propranolol or activation of phosphodiesterase by imidazol in the vascular wall causes potentiation of vasoconstriction brought about by prostaglandin E2. Thus the endogenous cyclic AMP either antagonizes the vasoconstrictor effect of prostaglandin E2, or the latter affects vascular smooth muscles by influencing the activity of enzymes that are responsible for the cyclic AMP level in the vascular wall. PMID- 6252983 TI - [Metabolic response of leukocytes as an index of the individual response of an animal to stress and traumatic shock]. AB - A relationship has been established between varying metabolic response of leukocytes to immobilization stress and severity of the shock progress. Initiation of the shock is accompanied by different response of animal leukocytes that correlates with the severity of the subsequent process. Formation of the resistance to shock is associated with an active glucose involvement into energy and plastic metabolic reactions, activation of the substrate-enzymic systems of glycolysis, pentose shunt, terminal stage of the respiratory chain, decreased rate of succinte dehydrogenation. PMID- 6252984 TI - [Biochemical characteristics of membrane fractions from different types of cerebral cortex synaptosomes]. AB - The activity of acetylcholinesterase (ACE) and Na, K-ATPase is distributed among three subfractions of synaptic membranes isolated from light (C) and heavy (D) synaptosomes of the optic area of the rabbit cerebral cortex. The levels of specific activity of both enzymes in C subfractions are similar to those in D subfractions. At the same time the specific activity of ACE and Na, K-ATPase in membrane fractions from both light and heavy synaptosomes is different. Such a biochemistry of subsynaptic components from certain brain structures favors studying a fine morphochemical organization of an isolated nerve terminal and its relationship with the activity of CNS in different functional states. PMID- 6252985 TI - [Ca2+ inhibition of adenyl cyclase of rabbit jejunal mucosa]. AB - Ca2+ ions at a concentration of 10-7--10-3 M inhibit adenylate cyclase of the rabbit jejunum mucosa (K0.5= =10-4 M). This effect is not modified after the membrane extraction by 10-3 M EDTA solution with a high or low ionic strength or after removal from the membrane preparation of Ca2+-dependent thermostable regulatory protein. The inhibition by Ca2+ions was discovered also in the presence of adenylate cyclase irreversible activators (guanylylimidodiphosphate and NaF), which points to the spontaneous interaction of Ca2+ ions with the catalytic subunit of the adenylate cyclase complex. PMID- 6252986 TI - [Increased immunologic reactivity against hepatoma 22A cells in MTV-infected C3H mice in comparison to MTV-free mice]. AB - Some tumors of no mammary tissue origin (sarcoma, hepatoma) grew more effectively in MTV-free mice (C3Hf) as compared with MTV-infected mice (C3H/He), whereas the tumors of mammary gland origin grew more rapidly in the latter ones. It has been shown that C3H/He mice develop a stronger specific immune reaction against hepatoma 22a cells than do C3H/f mice and that the animals of MTV-bearing subline exhibit a higher natural killer activity against these cells. PMID- 6252987 TI - [Depolarization of primary afferents and presynaptic inhibition of monosynaptic reflexes]. AB - In experiments on anesthetized spinal cats, perfusion of the lumbosacral spinal cord through the central canal with artificial cerebrospinal fluid containing ammonium ions led to reversible suppression of slow negative dorsal root potentials (DRP). The suppression of DRP proceeded in parallel to suppression of postsynaptic inhibition of motoneurons but was not related to a marked weakening of prolonged "presynaptic" inhibition of extensor monosynaptic reflexes produced by repetitive impulse volleys in group I flexor muscle afferents. It is concluded that primary afferent depolarization alone does not lead to presynaptic inhibition of synaptic transmission. A decisive factor for the inhibition might be the GABA-induced increase in chloride conductance of the presynaptic membrane, which, however, does not result in the terminal depolarizing current flow after the blockade of chloride pump with ammonium ions. PMID- 6252988 TI - [Changes in acetylcholinesterase and ATPase activity and certain structural features of the erythrocyte membrane in experimental myocardial ischemia]. AB - Acute heart ischemia induced by ligation of the left coronary artery is associated with variation in the activity of acetylcholinesterase, Na, K-ATPase and Ca, Mg-ATPase in rat erythrocytes. The maximum pronounced variations in the enzymatic activity and in the membrane capacity of erythroblasts for binding direct turquoise are recorded on the 7th day of the experimental myocardial infarction. PMID- 6252989 TI - [Effect of acetylcholine on cyclic guanosine monophosphate levels in the hearts of rats of different ages]. AB - The effect of various doses of acetylcholine on the content of myocardial cGMP was studied in rats of different age. The degree of changes was shown to depend on acetylcholine dosage and animals' age. Low doses produced more potent effect in adult rats. It is suggested that these features of alteration of cGMP content may be a reason for increased myocardial sensitivity to acetylcholine in old age. PMID- 6252990 TI - [Systemic blood diseases in inbred mouse strain CC57W]. AB - In "low cancer" CC57W mouse line studied over a period of 1944--1969 spontaneous leukemias occurred in 0.4--6.8%. During 1971--1976 the frequency of spontaneous leukemias amounted to 33%. Morbid anatomic and hematologic studies showed that aleukemic and subleukemic forms of chronic generalized reticulosarcomatosis with predominant affection of the lymphatic system accounted for the overwhelming majority of systemic diseases of the blood. Electron microscopy revealed virus like type C particles in the cells of the affected organs. PMID- 6252991 TI - [Effect of cyclic guanosine monophosphate on certain indices of muscle tissue carbohydrate metabolism during the wound process]. AB - The effect of intraperitoneal administration of cGMP (0.5 mg per animal) on carbohydrate metabolism of wound area muscle tissue was studied in experiments on rats with linear skin wounds. The content of glycogen, gluconeogenesis, activity of glycogen phosphorylase, lactate dehydrogenase and malate dehydrogenase were studied. Cyclic GMP induced a substantial activation of glycogen metabolism (elevation of gluconeogenesis, increase in the activity of glycogen phosphorylase) even the third day after the operation. The animals not given cGMP demonstrated such an activation only the fifth day following the operation. Under the effect of cGMP the activity of lactate dehydrogenase rose the third day after the operation. Thus cGMP administration to the animals with wounds leads to an earlier mobilization of energy resources thereby promoting the acceleration of wound healing. PMID- 6252992 TI - Regulation of platelet arachidonic acid oxygenation by cyclic AMP. AB - Intracellular cyclic adenosine monophosate (AMP) levels regulate the generation of thromboxane by platelets by inhibiting the hydrolysis of arachidonic acid from membrane phospholipids. However, there is conflicting evidence regarding the role of cyclic AMP in the control of the subsequent oxygenation of arachidonic acid by cyclooxygenase. We studoed the regulation of cyclooxygenase activity by agents that elevate platelet cyclic AMP (dibutyryl cyclic AMP and prostaglandins), measuring arachidonate-induced aggregation, O2 consumption, and malonaldehyde formation. In platelet-rich cyclic AMP. This inhibitory effect of cyclic AMP was absent in gel-filtered platelets suspended in buffer containing 0.5% albumin, and was progressively restored as plasma was added in increasing concentrations. Increasing the albumin concentration in platelet buffer suspensions likewise increased the ability of cyclic AMP to block the arachidonate-induced O2 burst and MDA production. We conclude that (1) the presence of plasma proteins is important in investigating platelet plasma milieu or at least in the presence of physiologic albumin concentrations. PMID- 6252993 TI - Prenatal diagnosis of beta-thalassemias by amniocentesis: linkage analysis using multiple polymorphic restriction endonuclease sites. AB - In order to assess the applicability of multiple restriction endonuclease analyses of amniocyte DNA to the prenatal diagnosis of beta-thalassemias in general, we studied 12 consecutive couples at risk. DNA of both members of the 12 couples and a previous offspring of each was analyzed for the presence of 4 polymorphic restriction endonuclease sites: the Hpa I site 3' to the beta-globin gene, the Hind III site in the G gamma gene, the Hind III site in the A gamma gene, and the Bam HI site 3' to the beta-gene. Linkage disequilibrium between these sites and beta A or beta thal genes was not found, presumably due to the heterogeneity of beta thal genes. However, the high frequency of polymorphism at these sites allowed differentiation of beta A-bearing chromosomes from beta thal or beta S-bearing chromosomes in both members of 6 couples. In these couples, complete prenatal diagnosis by linkage analysis of amniocyte DNA would be possible. In the remaining 6 couples, beta A and beta thal chromosomes could be discriminated in one member. In about 50% of the pregnancies of these couples, exclusion of beta-thalassemia is possible by this analysis. These data suggest that when linkage analysis of polymorphic restriction endonuclease sites is carried out, prenatal diagnosis of beta-thalassemia states can be accomplished by amniocentesis alone in 75% of pregnancies at risk. PMID- 6252994 TI - Effect of DEHP on adenine nucleotide translocase activity in isolated rat heart mitochondria. PMID- 6252995 TI - Primary reconstruction of perineal defect with a bilobed myocutaneous flap: case report. PMID- 6252996 TI - Further studies on opiate receptors that mediate antinoception: tooth pulp stimulation in the dog. AB - 1 The antinociceptive activities of morphine, codeine and dextropropoxyphene (micro-agonists), buprenorphine and Mr 2034 [(-)5,9-dimethyl-2 (tetrahydrofurfuryl)-2'-hydroxy-6,7-benzomorphan](k-agonists ) have been determined against nociceptive responses to electrical stimulation of the tooth pulp in the conscious dog. 2 Dose-dependent increases in nociceptive threshold were obtained for all of the analgesic drugs tested at doses within their antinociceptive range as determined in nociceptive pressure and chemical tests in rodents. PMID- 6252997 TI - Selenomethionine liver scanning in the diagnosis of hepatoma. AB - Liver subtraction scans using 99Tcm sulphur coloid and 75Se-selenomethionine were carried out in 58 patients with suspected hepatoma. Of the 18 patients with hepatoma proven by histology, 16 showed selective concentration of selenomethionine in the tumour, giving a true positive rate of 89%. Of the 40 patients who did not have hepatoma, 32 scans showed no evidence of selective concentration of selenomethionine, giving a true negative rate of 80%. The false positive rate was 8% in non-cirrhotic patients with focal disease, but 55% in patients with cirrhosis. It is concluded that combined scanning with this technique is useful in non-cirrhotic patients in distinguishing hepatoma from other causes of focal disease, but that the technique is not useful and frequently misleading in patients with cirrhosis. PMID- 6252998 TI - Angiographic feature of inflammatory fibrous histiocytoma. PMID- 6252999 TI - A study of childhood renal tumours using xenogeneic antiserum. AB - Fifty-six primary childhood renal tumours, 14 normal and 12 fetal kidneys were examined for their staining reaction with xenogeneic anti-Wilms' antiserum. The antiserum was raised by injecting Wilms' tumour extracts into 6-month-old rabbits which had been rendered tolerant in utero with pooled normal kidney extracts. Renal carcinomas, mesoblastic nephroma and a large proportion of tubular wilms' tumours were stained by the antiserum. In contrast, 6 of 7 bone-metastasising renal tumours of childhood (BMRTC) failed to fluoresce when treated with the antiserum, suggesting that the BMRTC has a different origin from the other childhood renal tumours studied. PMID- 6253000 TI - The human tumour xenograft--a valid model in experimental chemotherapy? AB - The chemotherapeutic response of a series of patients with bronchial carcinoma has been compared with the response of their xenografts established in immune suppressed mice. The in situ endpoint of growth delay in subcutaneous tumours was the main parameter used to assess xenograft response, but clonogenic cell survival studies were also performed to assess the extent of cell kill associated with in vivo responses. Histology, chromosome analysis and demonstration of ectopic hormone production indicated that the xenografts retained human morphology and functional behaviour. Clinical response was assessed by serial measurement of metastases. The chemotherapeutic validity of xenografts is supported by this study in which 21 separate responses in 16 patients and their respective xenografts were similar. Metastases regressed completely in 5 out of 7 patients with oat cell carcinoma. Xenografts derived from these were also highly responsive to similar chemotherapy. In contrast, minimal responses were observed in xenografts established from two chemoresistant patients. One large cell anaplastic, 3 squamous and 4 adenocarcinomas were universally chemoresistant in patients and their xenografts. It is concluded that the bronchial carcinoma xenografts broadly retained human morphology and functional behaviour, and reproduced the pattern of chemotherapeutic response of their source tumours. The present work suggests that the incorporation of human tumour xenografts into drug development programmes is justified, although their usefulness in a predictive capacity to select appropriate chemotherapy for individual patients remains limited. PMID- 6253001 TI - Assessment of the secretin provocation test in the diagnosis of gastrinoma. AB - The effect of intravenous secretin on plasma immunoreactive gastrin is presumed to improve diagnostic accuracy in patients with a gastrinoma. To investigate this further, the secretin provocation test was performed in control patients (n = 10), patients with a primary duodenal ulcer (n = 10), patients who had previously had surgery for a duodenal ulcer (n = 20), patients with symptomatic recurrent peptic ulceration (n = 50) and 2 patients with a histologically proved gastrinoma. It was found that the secretin test gave a false positive result in 3 out of 10 symptomatic duodenal ulcer patients, 2 out of 20 patients who had had previous duodenal ulcer surgery and were now asymptomatic and 15 out of 50 patients with recurrent peptic ulceration. Both gastrinoma patients had positive secretin tests but there were no obvious criteria that separated the gastrin response of a gastrinoma patient from those with primary or recurrent peptic ulceration. It is concluded that the secretin test is probably of little value in both the screening and the diagnosis of a gastrinoma. PMID- 6253002 TI - High fibre diet. PMID- 6253003 TI - Usefulness of transhepatic portal catheterization in the treatment of insulinomas. AB - Twenty-four per cent of beta-cell tumours require more than one operation to control the hypoglycaemic syndrome. Almost all of them are small insulinomas undetectable by palpation of the pancreas. Arteriography is too insensitive to detect non-palpable tumours. Transhepatic catheterization of the splenic and portal veins (TPC) can detect the position at which there is an abrupt increase in insulin level indicating the site of the tumour. Routine use of TPC allowed us to locate all 9 insulinomas in which this technique was employed, whereas of 15 patients not studied by TPC only 12 tumours were located at first operation, 2 of which were found by blind resection of the tail of the pancreas. We believe that routine application of TPC to all cases of suspected insulinoma would reduce the incidence of surgical failures, unsuccessful blind resections and lengthy trials of medical therapy before laparotomy. PMID- 6253004 TI - The value of polymixin B in endotoxaemia due to experimental obstructive jaundice and mesenteric ischaemia. AB - The role of polymixin B in endotoxaemia due to obstructive jaundice and mesenteric ischaemia has been examined. Rats made jaundiced by common bile duct ligation were challenged with intragastric endotoxin. Rats given polymixin B infusions had improved survival (11/15) compared with controls (4/14). Mesenteric ischaemia was induced in rats by clipping the mesenteric artery. Limulus assay revealed marked endotoxaemia in controls. Polymixin B infusions reduced the degree of endotoxaemia. Pre-treatment with non-absorbable intestinal antibiotics markedly reduced endotoxaemia. Polymixin B infusions gave no advantage of survival (3/10) compared with controls (2/10), but all animals pre-treated with intestinal antibiotics survived (12/12). The difference in results found between obstructive jaundice and mesenteric ischaemia may be due to different degrees of endotoxaemia. Polymixin B may have a place in the prophylaxis of endotoxaemia in clinical obstructive jaundice. PMID- 6253005 TI - An experimental study of the relationship between synergistic wound sepsis and suture materials. AB - In wounds on the back of guinea-pigs an inoculum of 6 x 10(5) of Escherichia coli and of Bacteroides fragilis produced a frank infection rate of 27 per cent. Addition of a catgut or a braided nylon tie statistically significantly increased the rate to 56 and 48 per cent respectively. Prolene and silk produced much smaller, non-significant rises. The rate with polyglycolic acid was 18 per cent which, though not statistically significant, suggests the possibility that this material produces conditions unfavourable to multiplication of bacteria that produce this type of infection. PMID- 6253006 TI - Dietary fibre and blood pressure. PMID- 6253007 TI - Benign intracranial hypertension and Cushing's disease. PMID- 6253008 TI - Staging lung cancer. PMID- 6253009 TI - Unprocessed bran and its effect on urinary calcium excretion in idiopathic hypercalciuria. PMID- 6253010 TI - A better system for polio vaccination in developing countries? PMID- 6253011 TI - Hormone receptors and human breast cancer. PMID- 6253012 TI - Unprocessed bran idiopathic hypercalciuria. PMID- 6253013 TI - Dietary fibre and calcium excretion in diabetes. PMID- 6253014 TI - Hormone receptors and human breast cancer. PMID- 6253015 TI - Can children catch leukaemia? PMID- 6253017 TI - Finger wrinkling after immersion in water. PMID- 6253016 TI - The neuropsychiatry of megaloblastic anaemia. AB - The neuropsychiatric states of 50 patients with vitamin B12 deficiency and 34 patients with folate deficiency presenting with megaloblastosis in a general hospital were examined and compared. Abnormalities of the nervous system were found in two-thirds of both groups. Peripheral neuropathy was the most common condition associated with vitamin B12 deficiency and affective disorder with folate deficiency. The proportions of patients with organic mental change were similar in the two groups. Subacute combined degeneration of the cord was an uncommon complication and occurred only in the patients with vitamin B12 deficiency. There was no relation between haematological and neuropsychiatric abnormalities. The neuropsychiatry of megaloblastic anaemia seen in this study of patients presenting to haematologists or general physicians contrasts with that reported previously, before haematological techniques for separating the two deficiencies were introduced. PMID- 6253018 TI - Management of acute stroke in the elderly. PMID- 6253019 TI - Site of action of intrathecal morphine. PMID- 6253020 TI - Nephroblastoma in infants, 1969-75: variations in treatment and survival. AB - In a series of 79 infants aged under 1 year with nephroblastoma diagnosed during 1969-75 all the patients underwent nephrectomy, 33 (42%) received a course of radiotherapy, and 49 (62%) received chemotherapy. The overall three-year survival rate for patients who survived at least one week after diagnosis was 65%. The corresponding rate for infants with stage I tumours was 76%. The survival rate in children with early-stage tumours was significantly higher in those who were treated by nephrectomy and chemotherapy alone compared with those who also received radiotherapy. In a large proportion of cases nephrectomy and chemotherapy together constituted sufficient treatment for the cure of infants with nephroblastoma, and in some instances nephrectomy alone proved adequate. There was no general tendency for children under 1 year old to be unable to withstand chemotherapy. PMID- 6253022 TI - Cimetidine and ranitidine in duodenal ulcer. PMID- 6253021 TI - Effect of guar crispbread with cereal products and leguminous seeds on blood glucose concentrations of diabetics. AB - To compare the effect on blood glucose concentrations of guar incorporated into crispbreads with that of unprocessed high-fibre foods groups of four to six diabetics took a total of seven test breakfasts on separate days. By comparison with a breakfast of wholemeal bread and cheese, guar crispbread combined with bread reduced the area under the glucose response curve to 51% (p < 0.05); bread and soya beans reduced the area to 65% (p < 0.05); guar crispbread with soya beans to 25% (p < 0.002); and soya beans with lentils to 29% (p < 0.002). Porridge and cornflake breakfasts showed no difference. The favourable results with leguminous seeds may not make such meals more acceptable than meals of guar products, but a combination of leguminous seeds and guar may allow smaller and more acceptable amounts of both to be used. PMID- 6253023 TI - HR 756--a new cephalosporin in the treatment of gonorrhoea caused by ordinary and penicillinase-producing strains of Neisseria gonorrhoeae. AB - HR 756, a new cephalosporin, was used in single intramuscular doses of 500 mg to treat 108 men and women with gonorrhoea caused by penicillinase-producing Neisseria gonorrhoeae (PPNG) and non-PPNG. Of 102 patients followed up, 99 (97.05%) were cured. Cure rates for PPNG infections and non-PPNG infections were 98.18% and 95.74% respectively. Few adverse side effects were recorded but possible cross-sensitisation with penicillin was observed. Clinical and laboratory antibiotic susceptibility results correlated well. It is concluded that this drug is safe and effective in treating both PPNG and non-PPNG infectons. PMID- 6253024 TI - Iconic reading in a case of alexia without agraphia caused by a brain tumor: a tachistoscopic study. PMID- 6253025 TI - Calcium localization in the sympathetic ganglion of the bullfrog and effects of caffeine. AB - The localization of Ca2+ in the bullfrog sympathetic ganglion was studied using electron microscopy with Oschman and Wall's technique. When the ganglion was incubated and processed in an extremely high Ca2+ solution (20 mM) for electron microscopy, electron-dense deposits (EDD) were found at or in the plasma membranes, subsurface cisterns and mitochondria of the postganglionic neurons. These EDD were proved to contain calcium by X-ray microprobe analysis. On the other hand, they were not significant in the preganglionic terminals except those in the synaptic vesicles. Addition of caffeine (10 mM) to the incubation media and fixatives caused a drastic decrease in number of EDD of the subsynaptic membranes and the subsurface cisterns. Caffeine also reduced, but less markedly, the size and number of EDD in mitochondria. Caffeine (10 mM) prolonged the afterhyperpolarization of an action potential, reduced the amplitude of the ACh (nicotinic) potential and induced slow rhythmic hyperpolarizations in a 20 mM Ca2+ solution. These effects of caffeine which were presumably the result of an increase in the intracellular free Ca2+ were discussed in relation to the morphological data. PMID- 6253026 TI - Does systemic morphine increase descending inhibitory controls of dorsal horn neurones involved in nociception? PMID- 6253027 TI - Ionic channel distribution and heterogeneity of the axon membrane in myelinated fibers. PMID- 6253028 TI - Autoradiographic studies with a behaviorally potent 3H-ACTH4--9 analog in the brain after intraventricular injection in rats. AB - Autoradiographic studies aimed at identifying target cells in the brain for ACTH like peptides were performed using (3H-7-Phe)-4-Met(O2),8-D-Lys, 9-Phe-ACTH4--9, a behaviorally potent analog of ACTH4--9. The 3H-peptide was injected into the lateral ventricle of hypophysectomized rats that were sacrificed 5, 30, 60, 180, and 240 min later. Dry-mount autoradiograms of brain showed the highest density of silver grains in the ventricular lumen and choroid plexus. In addition, radioactivity penetrated brain tissue as far as 100 microns from the ventricles, and was distributed predominantly over neuropil. Within 5 min after the injection, an intracellular concentration of radioactivity above background levels was observed in a small proportion of cells near the ventricles in the septum, caudate-putamen, preoptic area, hypothalamus, thalamus, amygdala, and hippocampus. The cellular labeling decreased in intensity at greater distances from the injection site and at longer survival intervals, and was no longer evident 4 hr after the injection. The labeled cells were usually small, dark, and often elongated, suggesting that ACTH peptides may act preferentially upon a morphologically distinct class of cells in the brain. PMID- 6253029 TI - Transmission processes in the ventrobasal complex of rat during the sleep-waking cycle. PMID- 6253030 TI - Successful prosthodontics for the general dentist. Tenth of a series. After-care of complete denture patients. PMID- 6253031 TI - Metabolic aspects of bone resorption in calcium-deficient lactating rats. AB - Lactating female rats were fed diets containing 1.0, 0.1, or 0.04% Ca for 21 days. Fat-free dry weight, ash weight, calcium and phosphorus content of the humerus, plasma calcium levels, and bone acid and alkaline phosphatase activities were compared to those of nonlactating rats fed the same diets. Bone, plasma, and urinary cAMP levels were also studied. Dietary calcium deficiency and/or lactation caused significant loss of bone mass from experimental animals. Urinary cAMP levels reflecting increased parathyroid activity were elevated by the stresses of lactation and calcium deficiency over those of control animals. Plasma and bone levels of cAMP were not different. Bone alkaline and acid phosphatase activities were affected only by the most extreme stress. The results demonstrated that the calcium-deficient lactating rat is an excellent model for bone resorption studies. PMID- 6253033 TI - Bovine papular stomatitis incidence in veterinary students. AB - Five cases of probable bovine papular stomatitis in faculty and students in a university veterinary clinic precipitated an intensive surveillance program. A senior class of veterinary medical students was questioned at the beginning of their clinical training to determine their history of exposure to cattle and presence of lesions resembling bovine papular stomatitis. Fifty-nine of the 115 students reported having had their hands in the mouths of cattle frequently. One of the 59 had experienced a hand lesion resembling bovine papular stomatitis. This class was maintained under close surveillance for bovine papular stomatitis like lesions during the final 12 months of their clinical experience in veterinary school. One case developed in 8483 person days spent in the three high risk areas of beef cattle service, dairy cattle service and large animal anesthesiology. These two bovine papular stomatitis cases compare in frequency with five class members who had been vaccinated as a result of exposure to rabid animals and two class members with brucella antibodies in their sera. The findings suggest bovine papular stomatitis infections are not unusual in veterinary students but the mild clinical manifestations make the condition relatively unimportant. PMID- 6253032 TI - Studies of the intercellular matrix of growth plates from dwarf and homozygous nonaffected Alaskan Malamutes: collagen and hexosamine. AB - This study was performed to compare the extractability of dwarf growth plate collagen and hexosamine and that of homozygous nonaffected Malamutes and to measure the activity of three of the enzymes involved in the post-translational modifications of the collagen molecule. No significant differences were found in the activity of prolyl hydroxylase or lysyl oxidase in the dwarf growth plates. Lysyl hydroxylase activity in the dwarf was decreased to 22% and 33% that of the activity present in the homozygous nonaffected growth plates. Amino acid analysis of the collagen isolated from dwarf growth plates failed to reveal any decrease in hydroxylysine content. Growth plates were extracted with either 1 M sodium chloride or 4 M guanidine hydrochloride. The extracts were applied to a DEAE cellulose column. Amino acid analyses of the material which did not bind to DEAE revealed a slight decrease in the amount of guanidine-extractable hydroxyproline in the dwarf but a 60-fold increase in the amount of salt-extractable hydroxyproline in the dwarf growth plates. Material which eluted with 1 M sodium choloride was analyzed for hexosamine. There was a 10-fold increase in the amount of salt-extractable hexosamine present in the dwarf growth plates, whereas no significant differences were observed in the guanidine-extracted material. Hexosamine analysis of the growth plates revealed a significant increase in the total amount of hexosamine present in the dwarf growth plates. SDS-polyacrylamide gels of the material which did not bind to DEAE as well as the pepsin digested, 0.9M sodium chloride precipitated collagen demonstrated the presence of only type II collagen. PMID- 6253034 TI - Detection of bovine leukemia virus by syncytium assay. AB - When various indicator cells, including virus transformed and nontransformed cells, were cocultivated with bovine leukemia virus-producing cells, strong positive syncytia formation was found in transformed cells one day after cocultivation. The results of comparison of bovine leukemia virus antibody titers and the detection of bovine leukemia by the syncytium assay showed 89% of serologically positive cows were positive for bovine leukemia virus, whereas no reactors were found in serologically negative cows. However, the frequency of bovine leukemia virus detection differed according to the difference of incubation periods in the syncytium assay. Therefore, it is important to choose the appropriate indicator cell and culture conditions for the detection of bovine leukemia virus in the syncytium assay. PMID- 6253035 TI - Specific fluorescein-labeled antibodies to bovine viral diarrhea virus prepared from sera of rabbits immunized with purified virus. AB - Specific fluorescein-labeled antibody conjugates to three strains of bovine virus diarrhea virus were prepared from hyperimmune rabbit sera. Viruses used to hyperimmunize the rabbits were purified by four different procedures. Conjugates were comparable in quality and specificity to conjugates prepared from serum of a calf hyperimmunized to bovine virus diarrhea virus in our laboratory. The latter conjugate was tested by Biologics Laboratories, National Veterinary Services, U.S.D.A., Ames, Iowa. PMID- 6253036 TI - Effect of fasting on Na-K-ATPase activity in rat small intestinal mucosa. AB - The effect of fasting on mucosal Na-K-ATPase activity in various regions of rat small intestine was investigated. Fasting (17--48 h) was associated with a consistent decrease in specific and total activity of Na-K-ATPase in the jejunum, the levels tending to rise more distally. No effect on the specific activities of Mg-ATPase or alkaline phosphatase was found. Fasting was also associated with incresed adrenocortical activity and with decreases in mucosal mass, protein content, and histological dimensions of the jejunum, no similar changes being found in the distal small intestine. Glucose ingestion prevented the decrease in jejunal enzyme activity associated with fasting and elevated levels in the mid and terminal small intestine of fed animals. These effects suggest that Na-K ATPase activity in small intestinal mucosa may be, in part, inducible. PMID- 6253037 TI - Adenosine receptor activation in human fibroblasts: nucleoside agonists and antagonists. PMID- 6253038 TI - Specific effects of alpha-D,L-aminoadipic acid on synaptic transmission in frog spinal cord. AB - The sucrose gap technique was employed to investigate both synaptic and amino acid evoked responses from motoneurones or primary afferents of frog spinal cord. alpha-D,L-Aminoadipic acid (alpha-D,L-AAD) selectively antagonized responses to acidic amino acids, especially aspartate. The drug was most effective in antagonizing the polysynaptic components of synaptic potentials evoked by dorsal root or lateral column stimulation but had little effect on their monosynaptic components. The ventral root dorsal root potential which is thought to be mediated by a pathway that does not involve acidic amino acids was insensitive to alpha-D,L-AAD. These data, which were confirmed by intracellular recording from motoneurones, provided further evidence for the role of acidic amino acids in polysynaptic pathways in frog spinal cord. PMID- 6253039 TI - Properties of Na, K-ATPase from the salivary glands of the ixodid tick Amblyomma hebraeum. PMID- 6253041 TI - Treatment of advanced endometrial adenocarcinoma with a combined cytotoxic therapy. Predictive value of cytosol estrogen and progestin receptor levels. AB - Twenty patients with advanced or recurrent endometrial adenocarcinoma were treated with combination chemotherapy consisting of Adriamycin, cyclophosphamide, 5-fluorouracil, and vincristine at three-week intervals. A minimum of four treatment courses was given in each case. There were five total and five partial responses (50% favorable response rate); progression of the disease was evident in seven cases (35%). Lung metastases responded significantly better (P < 0.01) than other lesions: seven out of nine lung metastases showed an objective remission, whereas only two out of 11 tumors in pelvic, abdominal, or retroperitoneal space responded. The response rate did not correlate with histologic grade of tumor differentiation, or the performance state and age of the patient. Cytosol estrogen and progestin receptor levels were measured in 15 cases from the carcinomatous endometrial tissue prior to therapy. Ten patients with low receptor values (estrogen and/or progestin receptors below 30 fmol/mg cytosol protein) had a significantly (P < 0.025) greater response rate (70%) than did patients with higher receptor values (both receptors above 30 fmol/mg protein, response rate 20%). Determination of only one of the two receptors did not differentiate the patients equally well, although the response rate tended to be better (0.05 < P < 0.1) in patients with a low level of either estrogen or progestin receptor (67% response rate) when compared with a 33% response rate in patients with a high level of the corresponding receptor. Our results suggest that the measurement of cytosol steroid hormone receptors has the potential to serve as a suitable indicator for selection of endocrine or nonhormonal chemotherapy for patients with advanced endometrial adenocarcinoma. PMID- 6253042 TI - Infantile digital fibromatosis. Ultrastructural, histochemical, and tissue culture observations. AB - Three cases of infantile digital fibromatosis were studied by electron microscopy, enzyme histochemistry, and tissue culture. The tumors were made up equally of myofibroblasts containing electron-dense inclusions which were composed chiefly of microfilaments measuring about 5 to 7 nm. Dense bodies usually observable in the smooth muscle cells were found in the bundles of these microfilaments and in the process of the inclusions, suggesting that these inclusions may represent an abnormal accumulation of contractile protein in the cytoplasm of tumor cells. Two cell lines were established from culture of the tumor cells, and the cultured cells also contained inclusion bodies showing the same morphologic characteristics as those of the original tumor cells. Lysosomal enzymes were abundant in the cultured cells, but they were scant in the cells of the fresh tissue specimens. Cocultivation of the cultured cells with human embryonic lung cells yielded no cytopathic effect. PMID- 6253040 TI - Clostridium perfringens in animal disease: a review of current knowledge. AB - The diseases caused by various types of Clostridium perfringens are critically reviewed in the light of current knowledge. Particular emphasis is placed on information concerning these diseases in Canadian livestock. There are two etiologically clearly-defined acute C. perfringens diseases recognized in Canada: hemorrhagic enteritis of the new born calf, caused by C. perfringens type C, and enterotoxemia of sheep, caused by type D. Clostridium perfringens type A may play a role as a secondary pathological agent in various disease conditions, such as necrotic enteritis of chickens. It may also cause wound infections and may provide a source for human food poisoning outbreaks. There appears to be a considerable lack of knowledge regarding the distribution of C. perfringens types, their pathogenesis, diagnosis and the incidence of diseases caused by this organism. PMID- 6253043 TI - Primary small cell carcinoma of the skin. AB - A case of primary small cell carcinoma of the skin is reported. The patient manifested intermittent, rapidly recurrent local disease which responded to irradiation and chemotherapy. There was no evidence of widespread dissemination during the course of the patient's illness, which terminated in a probable episode of sepsis due to leukopenia. Electron microscopic examination demonstrated rare clusters of dense-core ("neurosecretory") granules in cytoplasmic processes. Electron microscopic study is necessary in order to distinguish this tumor from other small cell neoplasms. However, detailed clinical investigation is necessary to rule out a possible primary source elsewhere, e.g., lung. PMID- 6253044 TI - Detection of alpha-lactalbumin in breast lesions and relationship to estrogen receptors and serum prolactin. AB - Alpha-lactalbumin, the B protein of lactose synthetase secreted by the mammary epithelial cells, was isolated and purified from fresh human milk and injected into rabbits for antibody production. Indirect immunofluorescence (IIF) was done on various types of breast lesions to assess the relationship, if any, between histologic type and production of alpha-lactalbumin. Fifty percent of fibroadenomas and fibrocystic disease and 63% of infiltrating ductal carcinoma showed positive reaction. No false positives were found on IIF of alpha lactalbumin of several tumors of nonmammary tissue. These findings suggest that IIF for alpha-lactalbumin may be helpful in ascertaining the site of origin of metastatic breast tumors. However, serum alpha-lactalbumin was detected by radioimmunoassay in only 10% of women with infiltrating ductal carcinoma, indicating that this may not be a useful marker for the presence of breast cancer at least by the method employed. This discrepancy between serum and tissue alpha lactalbumin may be due to the short half-life of serum alpha-lactalbumin or to the lack of secretion of the protein into the blood. There was no apparent relationship between the presence of estrogen receptors or serum prolactin and alpha-lactalbumin in the 27 mammary carcinomas investigated. PMID- 6253045 TI - Melanocytic bronchial carcinoid tumor. AB - A melanin- and serotonin-producing bronchial carcinoid tumor is described. Melanin synthesis by neoplastic cells also containing electron-dense core (neurosecretory granules was documented by electron microscopy and serotonin content was found by biochemical assay to be 201.2 micrograms/g wet weight of tissue. Simultaneous demonstration of "endocrine" properties with characteristics of a cell of neural-crest origin provides strongly confirmatory evidence for the APUD cell theory of Pearse and makes an interesting commentary in regard to general theories of neoplasia. PMID- 6253046 TI - Tubular carcinoma developing within a recurring cystosarcoma phyllodes of the breast. AB - Malignant alteration in cystosarcoma phyllodes is uncommon and almost always confined to the stromal component. A rare case of recurring cystosarcoma is reported. In the first recurrence, lobular carcinoma in situ was present within the tumor and the second recurrence revealed tubular carcinoma within the cystosarcoma. Epithelial proliferation of various sorts is not uncommon in cystosarcomas but only two previous instances of infiltrating carcinoma have been observed within these tumors. The problem of mammary carcinoma coexisting with cystosarcoma is reviewed and comparisons are made with a closely related neoplasm, the fibroadenoma. PMID- 6253047 TI - Results of radiation therapy in the treatment of epithelial carcinoma of the ovary. AB - Between 1967 and 1976, 82 patients who had epithelial carcinoma of the ovary and were treated with surgery and postoperative radiation therapy, respectively, were studied. Of these patients, 35% had Stage I disease, 16% Stage II, 45% Stage III, and 4% Stage IV. Serous cystadenocarcinoma was the histologic cell type in 54% of the patients, and mucinous cystadenocarcinoma was involved in 24%. Of the tumors, 35% were Grade 1, 34% Grade 2, 18% Grade 3, and 13% were unspecified. Survival at five years was 96% for Stage I patients, 60% for Stage II, and 60% for Stage III. No stage IV patient survived past two years. Stage III patients with no palpable tumor prior to radiation therapy did well, with 80% alive at more than two years, while only 10% of Stage III patients with palpable tumors prior to radiation therapy are alive. Patients with Stage III disease treated by whole-abdominal irradiation with a pelvic boost did better than those who received 3,000 rad or less to the pelvis. Radiation therapy continues to be an important treatment modality in epithelial carcinoma of the ovary, particularly in patients with minimal tumor burden. PMID- 6253048 TI - Enzyme activities in human fetal and neoplastic tissues. AB - The concentrations of ten or 12 enzymes involved in the metabolism of DNA, collagen, amino acids, or glucose have been determined in variants of human intestinal and pulmonary tissues. In comparison to nonneoplastic adult colon, normal fetal colon had elevated concentrations of thymidine kinase, peptidyl proline hydroxylase, phosphoserine phosphatase, ornithine transcarbamylase, gamma glutamyl transpeptidase, and ornithine aminotransferase. Raised activities of the first five of these enzymes, and of hexokinase, glucose-6-phosphate dehydrogenase, and pyrroline-5-carboxylate reductase distinguishes neoplastic from nonneoplastic sections of adult colon. Study of a wide range of pulmonary specimens permitted comparisons of different types of tumors, and revealed some subtle differences between lungs of noncancer patients and nonneoplastic portions of host lungs. The concentrations of eight previously identified enzymic indicators were less in moderately or well differentiated than in poorly differentiated pulmonary adenocarcinomas. The latter differed from epidermoid carcinomas (also poorly differentiated) by containing lower concentrations of thymidine kinase (both soluble and particulate) and hexokinase. PMID- 6253049 TI - ACTH, ADH, and calcitonin concentrations as markers of response and relapse in small-cell carcinoma of the lung. AB - The ectopically produced polypeptide hormones ACTH, ADH, and calcitonin were investigated as tumor markers in patients with small-cell carcinoma of the lung (SCC). Plasma ADH concentrations were evaluated separately as well as in relation to concomitantly obtained plasma osmolality levels. No significant nor consistent changes of marker concentrations caused by lysis of tumor cells were found immediately after administration of cytotoxic drugs. After tumor regression, plasma ACTH and serum calcitonin concentrations and inappropriate ADH secretion (plasma ADH levels inappropriately high compared with plasma osmolality) became normal in most cases; however, progressive disease was not followed consistently by changes in plasma ACTH concentrations and occurrence of inappropriate ADH secretion. Contrary to this, among 12 patients with disease progression, serum calcitonin levels increased in ten patients and plasma ADH levels increased in 11 patients. In most cases, however, these changes were only moderate, and serum calcitonin concentrations were found to be increased after tumor regression in patients who had normal pretreatment levels. It is concluded that decisions on treatment of patients with SCC cannot exclusively be based on changes in the concentrations of the polypeptide hormones that might be of ectopic origin. PMID- 6253050 TI - Elevated carcinoembryonic antigen levels in the milk of a nursing mother with inoperable breast cancer. AB - Carcinoembryonic antigen (CEA) determinations performed in the milk of a nursing mother with an inoperable breast cancer revealed a 10-15-fold higher level compared with CEA levels in the milk of healthy nursing women. CEA was highly elevated in the milk of the tumor-bearing breast (1100 +/- 100 ng/ml) and moderately elevated in the milk of the clinically nonaffected breast (700 +/- 50 ng/ml). However, serum CEA levels were within normal range (9.8 +/- 0.5 ng/ml). The various theoretical and practical implications of this finding, including considerations for early breast cancer detection, are discussed. PMID- 6253051 TI - Nasopharyngeal carcinoma in Alaskan Eskimos Indians, and Aleuts: a review of cases and study of Epstein-Barr virus, HLA, and environmental risk factors. AB - The records of thirty-one patients with nasopharyngeal carcinoma (NPC) diagnosed from 1966 through 1976 among the Alaskan native population (Eskimo, Aleut, Indian) were reviewed. There were 25 males and six females, which results in relatively high incidence rates per 100,000 of 13.5 for males and 3.7 for females. Clinical and pathologic features were similar to those found among southern Chinese NPC patients. Five-year survival rate was 48%. Antibodies to Epstein-Barr virus were higher in NPC patients than in patients with other tumors or matched controls. On histocompatibility testing Sin-2 was not detected, nor was there significantly increased frequency of A2. Instead, BW40 and a second locus blank occurred more often among NPC patients than among other groups. In response to a questionnaire, NPC patients more often reported use of salt fish in the childhood diet, smoking of cigarettes, and exposure to noxious inhalants than did controls, but the differences were not statistically significant. PMID- 6253052 TI - Lung tumors induced by chronic inhalation of 1,2-dibromo-3-chloropropane in B6C3F1 mice. AB - 1,2-Dibromo-3-chloropropane (DBCP) was inhaled by B6C3F1 mice of each sex at concentrations of 0.6 or 3.0 ppm for 6 h/day, 5 days/week, for 103 weeks. Untreated controls consisted of 50 mice of each sex. All surviving animals were killed at 104 weeks. Survival in the high-dose groups of female mice was significantly shorter than that in the corresponding controls. Alveolar bronchiolar adenomas or carcinomas occurred in both male and female mice with dose-related trends (P < 0.007) in males and (P < 0.002) in females. Papillary carcinomas in the lung occurred in low-dose female mice at an increased incidence compared with controls (P < 0.006). Many induced tumors were morphologically different than those in controls. PMID- 6253054 TI - Effects of retinoic acid on plasminogen activator and mitogenic responses of cultured mouse cells. AB - Treatment of simian virus 40-transformed 3T3 cells with 1 microM beta-all-trans retinoic acid (RA) resulted in a 5- to 6-fold enhancement of plasminogen activator (PA) release. Intracellular PA levels rose to twice control levels. Confluent 3T3 cells were less responsive to RA. In 6 of 10 experiments, no increase in 3T3 cell PA levels was noted, although up to a 2.5-fold enhancement of PA elaboration has been observed in some experiments at a dose of 10 microM RA. Simultaneous treatments of 3T3 cells with 10 microM RA and 2.1 to 9.3 mM Ca2+, 5 to 40 ng phorbol myristate acetate per ml, or 150 to 600 ng Fraction I from lactalbumin hydrolysate (Fl) protein per ml indicated that RA potentiated the PA stimulatory activities of these agents. Extracellular PA levels of RA treated cells increased by 4 to 10 times the amount of increase observed for Ca2+, PMA, or Fl alone. A potentiating activity of RA was also evident when quiescent 3T3 cells were pretreated with 10 microM RA and then stimulated to synthesize DNA with Ca2+, PMA, or Fl. For RA-pretreated cells, an increased percentage of nuclei was labeled with [3H]thymidine (24 hr) in response to doses of the three mitogens which were ineffective without RA pretreatment (2.4mM Ca2+, 5 ng PMA per ml, or 150 ng Fl protein per ml). Additional experiments have indicated that, like platelet extracts, Ra renders quiescent 3T3 cells competent to synthesize DNA in response to the progression factors of human plasma as defined by Pledger et al. (Proc. Natl. Acad. Sci. U. S. A., 74: 4481-4485, 1977). Pretreatment of quiescent 3T3 cells for 6 hr with 10 microM RA resulted in a greater than 4-fold increase in the percentage of cells which incorporated [3H]thymidine in response to a 36-hr treatment with 10% human plasma, as compared to cells treated with human plasma alone. Thus, under certain conditions, RA may have cell-activating properties, and caution should be exercised with regard to its suggested use as an antitumor agent. PMID- 6253053 TI - Induction of local epidermal papillomas and carcinoma by selected nitrosamines. AB - Weekly cutaneous application of N-nitrosobis (2-oxopropyl)amine (BOP) at a dose of 2 mg/application to the neck area resulted in the induction of local papillomas and carcinomas in 80% of Syrian hamsters as early as 19 weeks post treatment. In addition, a few tumors of internal organs (predominantly in the liver) were also found. N-Nitroso(2-hydroxypropyl) (2-oxopropyl)amine (HPOP), a common metabolite of BOP and BHP, was also found to be an epidermal carcinogen at a dose of 3.8 mg/application. N-Nitrosobis(2-hydroxypropyl)amine (BHP), however, failed to induce any epidermal lesions, when applied similarly at a much higher dose level (%) mg/animal/week). In contrast to BOP and HPOP, BHP induced a high incidence of tumors in internal organs, especially pancreatic cancer, which was the only induced tumor in 5 animals. Skin absorption studies demonstrated that BHP, but not BOP is rapidly absorbed and was detectable in the blood in concentrations of up to 5.5 mug/ml as early as 15 min after carcinogen administration. The possible reasons for the differing effects of BHP and BOP upon hamster skin are discussed. PMID- 6253055 TI - Comparative effects of estrogen and antiestrogens on enzyme activities in R3230AC rat mammary tumors and uteri of tumor-bearing animals. PMID- 6253056 TI - Pyrimidine dimer formation and repair in human skin. AB - Cyclobutyl pyrimidine dimers have been detected in the DNA of human skin following in vivo irradiation with suberythemal doses of ultraviolet (UV) radiation from FS-20 sun lamp fluorescent tubes. Dimers were assayed by treatment of extracted DNA with Micrococcus luteus UV-specific endonuclease, alkaline agarose electrophoresis, and ethidium bromide staining. This technique, in contrast to conventional dimer assays, can be used with nonradioactive DNA and is optimal at low UV light doses. M. luteus endonuclease-sensitive sites were determined after exposure of untanned skin in two volunteers to UV light (0.97, 1.94, or 3.88 X 10(3) J/sq m; lambda, 290 to 360 nm). At 20 min postirradiation (dose, 1.94 X 10(3) J/sq m), fewer M. luteus endonuclease-sensitive sites were found in the DNA than immediately after the irradiation. Even fewer endonuclease sensitive sites were found at 20 min when the UV-irradiated skin was subsequently irradiated with visible light than when the area was kept in the dark. These data suggest that some dimer disappearance by excision repair occurs within 20 min of UV irradiation and that photoreactivation of dimers can make a contribution to the total repair process. PMID- 6253057 TI - L-Ethionine as an inducer of differentiation in human promyelocytic leukemia cells (HL-60). AB - The methionine analog, L-ethionine, induces morphological and biochemical changes in cultured HL-60 cells which are indicative of myeloid maturation. After 3 to 5 days of growth in the presence of L-ethionine, the majority of cells have enhanced phagocytic ability. The percentage of cells in the culture which bear complement receptors and which can respond to 12-O-tetradecanoylphorbol-13 acetate with respiratory burst activity increases more than 3-fold. Since the cells fail to become adherent and lose nonspecific esterase activity, we conclude that L-ethionine, like dimethyl sulfoxide, induces granulocytic differentiation of HL-60 cells. PMID- 6253058 TI - Characterization of estradiol, progesterone, and prolactin receptors in nitrosomethylurea-induced mammary tumors and effect of antiestrogen treatment on the development and growth of these tumors. PMID- 6253059 TI - Cerebrospinal fluid polyamines in patients with Glioblastoma multiforme and anaplastic astrocytoma. AB - Eighteen cerebrospinal fluid polyamine determinations in 12 patients with glioblastoma multiforme and 76 determinations in 37 patients with anaplastic astrocytoma were evaluated. Cerebrospinal fluid polyamine levels showed no significant relationship to the degree of malignancy or to enhanced tumor volume or volume of tumor central low density as determined by contrast-enhanced computerized tomography. A significant correlation was found between polyamine levels and the proximity of the tumor to the cerebral ventricles. Polyamine levels were correlated with clinical status as determined by neurological examination, radionuclide scan, and computerized tomography. Compared with those of stable patients, cerebrospinal fluid polyamine levels were significantly elevated in patients with recurrent tumors; however, elevation of polyamine levels did not appear to precede tumor recurrence. A large fraction of the results were false-positive or false-negative results. In contrast to our findings in patients with medulloblastoma, it appears that cerebrospinal fluid polyamine levels determinations may be of little use for monitoring tumor progression in patients with glioblastoma multiforme and anaplastic astrocytoma. PMID- 6253060 TI - Metabolism and biological activity of 5'-deoxy-5-fluorouridine, a novel fluoropyrimidine. AB - 5'-Deoxy-5-fluorouridine (5'-dFUrd; Roche 21-9738) is a recently synthesized antineoplastic agent with therapeutic potential. The sensitivity of Ehrlich ascites tumor cells in CF-1 mice to 5'-dFUrd, as well as to 5-fluorouridine, was established. 5'-dFUrd was a more effective antitumor agent and was less toxic over a wide dosage range (50 to 400 mg/kg) than the other agents tested as measured by: (a) the ability to prevent gross development of inoculated tumor; (b) 45-day survival; and (c) weight change over the treatment period. With use of these sensitive tumor cells, the intracellular metabolism of 5'-dFUrd in vitro was investigated. Utilizing liquid chromatographic methodology for separation of acid-soluble metabolites, the only detectable metabolic products of 5'-dFUrd were FUra, 5-fluorouridine 5'-monophosphate, and 5-fluorouridine 5'-triphosphate. Novel metabolites of 5'-dFUrd were not detectable in the acid-soluble fraction or in plasma isolated from mice given [14C]5'-dFUrd. The formation of FUra appears to result from the action of nucleoside phosphorylase. 5'-dFUrd was shown to have a Km of 0.633 mM for this enzyme isolated from Ehrlich ascites tumor cells, an affinity similar to that for 5-fluoro-2'-deoxyuridine (Km, 0.278 mM) but much lower than that for 5-fluorouridine (Km, 0.049 mM). Incorporation of radiolabeled drug into the acid-insoluble fraction (representing greater than 95% incorporation into RNA) was also significant. 5-Fluoro-2'-deoxyuridine 5' monophosphate (FdUMP) was not detectable as an acid-soluble metabolite. However, significant inhibition of thymidylate synthetase activity was detectable by 20 min in cells incubated with 30 microM 5'-dFUrd, suggesting that FdUMP was produced. The production of both 5-fluorouridine 5'-triphosphate and FdUMP appears dependent on the initial expansion of the FUra pool. This correlates with the inability of 5'-dFUrd to form nucleotide directly due to the absence of a 5' hydroxyl group. It is concluded that the antineoplastic activity of 5'-dFUrd may be dependent on its enzymatic conversion of FUra. The basis for the possible increase in therapeutic index compared with other fluoropyrimidines may involve the rate and duration of the production of the biologically active nucleotides 5 fluorouridine 5'-triphosphate and FdUMP. PMID- 6253061 TI - Stimulation of melanogenesis in a human melanoma cell line by retinoids. AB - Retinoic acid was found to be a potent stimulant of pigmentation in human Hs939 melanoma cells. Exposure to 1 microM retinoic acid for longer than four days caused both a decrease in the rate of cell proliferation and a concomitant increase in melanogenesis. These effects of retinoic acid progressed lin-early in a time-dependent and a dose-dependent fashion such that at the end of a seven-day treatment cell growth was inhibited by approximately 65%, and both melanin content and tyrosinase activity increased more than three-fold over the control. Interpolation of the dose-response curves indicated that 3 nM retinoic acid would cause half-maximal melanogenesis stimulation. No elevation in the level of cyclic adenosine 3':5'-monophosphate could be detected in the melanoma cells following various periods of exposure to retinoic acid, and the cells were unresponsive to alpha-melanocyte-stimulating hormone. In the presence of the tyrosinase inhibitor phenylthiocarbamate, retinoic acid was capable of inhibiting cell proliferation without enhancing melanin synthesis. The tumor promoter phorbol myristate acetate did not affect either the proliferation or the differentiation of the Hs939 melanoma cells. However, the enhancement of melanogenesis by 1 microM retinoic acid was inhibited by 66% in the presence of 0.1 microM phorbol myristate acetate. The tumor promoter did not reverse the growth-inhibitory effect of retinoic acid. Phorbol, a non-tumor promoter, was effective. Other retinoids, such as 13-cis-retinoic acid, retinyl acetate, nd the trimethylmethoxyphenyl analog of retinoic acid, also inhibited the proliferation and enhanced melanin production in the Hs939 cells. In contrast, retinyl palmitate, the phenyl analog of retinoic acid, and the pyridyl analog of retinoic acid were ineffective. PMID- 6253062 TI - Intervening DNA insertions and the alteration of gene expression by carcinogens. PMID- 6253063 TI - Sensitivity of leukemic human null lymphocytes to deoxynucleosides. AB - The growth of cultured leukemic T-lymphocytes is readily inhibited by deoxynucleosides, particularly thymidine, deoxyguanosine, and deoxyadenosine. By contrast, Epstein-Barr virus-transformed B-lymphocytes are relatively resistant to deoxynucleosides. Growth inhibition correlates with the development of high deoxyribonucleoside triphosphate pools following exposure to deoxynucleosides. Leukemic T-lymphocytes are deficient in ecto-5'-nucleotidase (5'-ribonucleotide phosphohydrolase, EC 3.1.3.5) activity, and it has been postulated that deficiency of this enzyme decreases the capacity of these cells to degrade deoxyribonucleotides, rendering them sensitive to deoxynucleosides. We find that the sensitivity of cultured null-type leukemic lymphocytes to growth inhibition of deoxynucleosides is similar to that of T-cells. However, the null cells contain normal levels of ecto-5'-nucleotidase. We infer that ecto-5'-nucleotidase deficiency does not have a central role in determining the deoxynucleoside sensitivity of leukemic lymphocytes. PMID- 6253064 TI - Expression of a cell surface glycoprotein (p180) related to cell-substratum adhesion during differentiation of mouse myeloid leukemia cells. AB - Mouse myeloid leukemia M1 cells were induced to differentiate in vitro into macrophages and granulocytes by various inducers including ascitic fluid. Differentiated M1 cells induced with ascitic fluid expressed a differentiation associated cell surface glycoprotein with a molecular weight of 180,000 (p180), which can be labeled by lactoperoxidase-catalyzed radioiodination or metabolic labeling with L-[14C]fucose. p180 was also induced by treatment with conditioned medium of hamster embryo cells, dexamethasone, dibutyryl cyclic adenosine 3':5' monophosphate, and prostaglandin E1. Ascitic fluid, conditioned medium of hamster embryo cells, and dexamethasone induced all the differentiation-associated properties tested, whereas dibutyryl cyclic adenosine 3':5'-monophosphate and prostaglandin E1 induced lysozyme activity and adhesiveness to the substratum but not phagocytosis, locomotive activity, Fc receptors, or morphological changes. The adherent cells induced by dibutyryl cyclic adenosine 3':5'-monophosphate produced a large amount of p180, while the floating cells produced very little, but no difference was detected in the lysozyme activities of the two cell types. These results suggest that p180 is associated with cell-substratum adhesion of differentiated M1 cells. PMID- 6253065 TI - The search for viruses as etiological agents in leukemia and malignant lymphomas: the role of the happy accident and the prepared mind. PMID- 6253066 TI - Treatment of small cell undifferentiated carcinoma of the lung: update of recent results. PMID- 6253068 TI - Fat induced hypertension in rabbits. Effects of dietary fibre on blood pressure and blood lipid concentration. AB - Rabbits were fed diets containing 200 g.kg-1 coconut oil, palm oil, or safflower oil. Some of the diets also contained 200 g.kg-1 cellulose. The blood pressure was measured daily by a non-invasive technique for the 2 month duration of the experiment. Blood samples were drawn after an overnight fast at intervals during the experiment and analysed for lipids. Blood pressure was always increased by a fat-enriched diet. This effect was diminished and delayed by adding cellulose to the diets, though cellulose itself had no effect on the blood pressure in the absence of fat. There was a modest negative correlation between fasting serum triglyceride concentration and the blood pressure in animals fed fat enriched diets without added cellulose, but not in animals fed diets containing both fat and cellulose. These results coupled with those of Wright, Burstyn and Gibney may serve partly to explain the observation that vegetarians have lower blood pressures than omnivores, the latter consuming diets which are relatively richer in fats and poorer in fibre than the former. PMID- 6253067 TI - Single-agent and combination chemotherapy for extensive non-small cell carcinomas of the lung. AB - One hundred and twenty-four patients with extensive bronchogenic carcinoma were randomized to one of three chemotherapeutic regimens. Forty-one patients received cyclophosphamide (600 mg/m2 every 3 weeks) (group 1); 47 patients received cyclophosphamide (600 mg/m2 every 3 weeks) and CCNU (70 mg/m2 every 6 weeks) (group 2); and 36 patients received cyclophosphamide (600 mg/m2 every 3 weeks), CCNU (70 mg/m2 every 6 weeks), and doxorubicin (40 mg/m2 every 3 weeks) (group 3). The objective response rates were 5%, 8%, and 6% in groups 1, 2, and 3, respectively (P greater than or equal to 0.3). Median survival times were 20.5 months (group 1), 17.8 months (group 2), and 18.8 months (group 3). There was no significant difference in median survival between groups (P greater than or equal to 0.4). Responders in each group survived longer than nonresponders. Hematologic toxic effects were severe in group 3 and moderate in group 2. Since combination chemotherapy with cyclophosphamide and doxorubicin or cyclophosphamide, doxorubicin, and CCNU is not superior to cyclophosphamide as a single agent and is associated with greater toxicity, these combinations are not recommended as therapy for extensive bronchogenic carcinoma. PMID- 6253070 TI - Accumulation of technetium-99m pyrophosphate in experimental infarctions in the rat. AB - Cardiac accumulation patterns of pyrophosphate labelled with techetium-99m (TcPyP) in rats one hour to 7 days after coronary artery ligation were studied by light microscopy, myocardial scintigraphy, imaging the isolated heart and by direct measurement of tissue activity. Results suggest that myocardial cells taking up TcPyP are irreversibly damaged and that the disappearance of TcPyP uptake coincides with the removal of necrotic cells by phagocytes. PMID- 6253069 TI - Haemodynamic effects of angiotensin converting enzyme inhibition after cardiopulmonary bypass in dogs. AB - Recent studies have suggested a possible causative relationship between elevated plasma levels of Angiotensin II (AII) and the vasoconstriction associated with conventional cardiopulmonary bypass. The haemodynamic effects of SQ14225, a specific angiotensin converting enzyme inhibitor, have been studied in a group of five dogs submitted to a 60 min period of cardiopulmonary bypass (CPB). A 20 min infusion of SQ14225 in a dose of 2 microgram .kg-1 .h-1 was administered to each dog 2 h after the end of the period of CPB. Measurements of peripheral vascular resistance index (PVRI), cardiac index (CI) and plasma levels of Angiotensin II were obtained at the start and end of the infusion period. The results in the five blocked dogs were compared with a control series of ten unblocked dogs submitted to an identical cardiopulmonary bypass regine. In the blocked dogs, PVRI fell significantly during infusion of SQ14225 from 38.27 units to 21.70 units (P <0.01). There was a simultaneous significant increase in cardiac index from 3.00 to 3.98 litre.m2 .min-1 (P <0.01). Plasma Angiotensin 11 levels fell in the blocked dogs from 57 to 11.5 pg.cm-2 during the infusion period (normal levels <15 pg.cm-3). In the control unblocked dogs, there was no corresponding fall in PVRI, no rise in cardiac index, and no fall in elevated plasma AII levels. The difference between the groups were statistically highly significant (P <0.005). These results indicate that reduction in elevated plasma AII levels after CPB using converting enzyme inhibitor SQ14225 is associated with a significant fall in peripheral vascular resistance and a significant rise in cardiac index. In addition, the study confirms the causative relationship between elevated plasma levels of Angiotensin II and the increased vasoconstriction associated with non-pulsatile CPB. PMID- 6253071 TI - Role of vesicles on the transport and secretion of exocellular enzymes by yeast. PMID- 6253072 TI - Solubilization and purification of 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP-A) from bovine cerebral white matter--a review. PMID- 6253073 TI - Dynamical model of cholinergic synapse transmission. PMID- 6253074 TI - The cell types in the adenohypophysis of the South-American lungfish, Lepidosiren paradoxa, with special reference to immunocytochemical identification of the corticotropin-containing cells. AB - The histological features and distribution of cell types in the distal lobe of Lepidosiren resemble those of Protopterus. Three "basophilic" cell types are described, whereas the identification of two acidophilic cell types is uncertain. In the intermediate lobe two cell types have been found. Anti-(1-24)ACTH IgG was used in the unlabeled antibody-enzyme method to identify corticotropin-containing cells in the adenohypophysis of Lepidosiren with light and electron microscopy. Corticotropin was demonstrated in cells of the distal lobe and the intermediate lobe. The staining reaction in the distal lobe is localized in the rostrally distributed lead-hematoxylin positive cells. At the ultrastructural level the immunoreaction in these distal lobe cells is localized on polymorphic granules ranging from 130 to 210 nm. Absorption experiments show that the immunoreactive cells in the distal lobe contain at least residues 1-3 and 14-17 of the naturally occurring corticotropin hormone, while the intermediate lobe cells contain alpha MSH or at least residues 1-3 of ACTH. The plasma level of corticotropin was determined to be 71 ng/l by means of radioimmunoassay (RIA). PMID- 6253075 TI - Periodicities and tandem repeats in a Balbiani ring gene. AB - The Balbiani ring (BR) DNAs show prominent periodicities of restriction enzyme sites. Studies using a cloned fragment of the BRc gene strongly suggest that these periodicities reflect the existence of tandemly repetitive sequences within BR DNA. Tandem repeats measuring 54-58 bp have been demonstrated by partial sequence analysis of the BRc clone; the restriction site periodicities suggest the existence of additional 175 (= 3 X 58) and 1050 (= 6 X 175) bp repeat units. The short, medium and long repeats (58, 175 and 1050 bp, respectively) show sequence homology. Constrained unequal crossing over (resulting from misalignment of repeat arrays, usually by one repeat) is proposed as the mechanism for evolution of short, medium and long repeats from each other, in a manner analogous to evolution of satellite DNA sequences. Paradoxically, the dominant restriction site periodicities appear to be more conservative than might be expected on the basis of the overall sequence divergence between the sequenced repeats. This may be a consequence of functionally important, long-range amino acid or oligopeptide periodicities (for example, Asp x Ser or Glu x Ser corresponding to Hinf I sites) in the BRc protein product, in conjunction with preferential use of certain synonymous codons. PMID- 6253076 TI - The gross anatomy of a tRNA gene cluster at region 42A of the D. melanogaster chromosome. AB - The sequence organization and positions of the tRNA genes in a tRNA gene cluster at chromosomal region 42A of the D. melanogaster (Dm) genome have been studied by recombinant DNA methods. A set of overlapping inserts of Dm DNA cloned in a lambdoid vector and extending in both directions from the Drosophila tRNA gene bearing fragment of plasmid pCIT12 has been isolated by the procedure of "chromosomal walking." The isolated region has a total length of 94 kb of which a central 46 kb region contains eight tRNAAsn genes, four tRNA2Arg genes, five tRNA2Lys genes and one tRNAIle gene. The genes are irregularly spaced and transcribed from both strands; they occur to some extent in subclusters. Thus this sequence organization is totally different from the tandem repeat organizaiton seen in many 5S rRNA gene clusters of higher eucaryotes and in one Xenopus rRNA gene clusters of higher eucaryotes and in one Xenopus tRNA gene cluster. PMID- 6253077 TI - Definition of a novel promoter for the major adenovirus-associated virus mRNA. AB - A 660 nucleotide adenovirus-associated virus type 2 (AAV2) DNA fragment which encodes the 5' terminal leader and the entire intervening sequence of the major viral mRNA has been cloned into pBR322, and its primary sequence has been determined. The 5' terminal viral mRNA sequence was deduced by sequencing the reverse-transcriptase cDNA extension product of a 5' end-labeled DNA primer complementary to the RNA 5' terminal region. From combined DNA and RNA sequence analyses (which confirm our previous mapping data) we conclude that the major AAV2 transcript contains a 5' terminal leader sequence about 55 nucleotides in length encoded from a continuous region of DNA (near position 39 on the viral genome) 320 bases from the RNA body. The DNA sequences of the splice junctions are similar to those found for other class II genes. No other nucleotide sequence, indicative of promotion at another (upstream) site, is present at the 5' terminus. The DNA region encoding and flanking the leader sequence displays structural features expected for a class II gene promoter, including the canonical ATATAA sequence 23-25 bases upstream from the presumed initiation site. When the cloned viral DNA fragment is transcribed in vitro by RNA polymerase II in a cell-free system, a transcript is produced with a 5' end that is similar or identical to that found on the in vivo mRNA. Taken together these data strongly suggest that the major polysomal RNA may be generated from a transcription unit with a promoter at position 39, even though this transcription unit is part of a larger transcription unit with an upstream promoter near position 6. This indication of overlapping transcription units with independent promoters provides a major new insight into parvovirus gene expression. PMID- 6253078 TI - Molecular engineering of the herpes simplex virus genome: insertion of a second L S junction into the genome causes additional genome inversions. AB - We have developed a technique for the insertion of any DNA fragment into the herpes simplex virus (HSV) genome at specific sites. This technique was used to resolve a specific problem concerning the isomerization of the HSV genome. Briefly, HSV DNA consists of four isomers differing in the orientation of two covalently linked components, L and S, relative to each other. Each component consists of unique sequences flanked by inverted repeats. To determine whether the isomerization of HSV DNA is the result of generalized recombinatin between homologous reiterated sequences in the inverted repeats or the result of site specific recombination, we constructed plasmids in which DNA fragments derived from various regions of the viral genome were inserted in both orientations into the thymidine kinase gene, rendering it nonfunctional. The HSV DNA sequences in the plasmids were then recombined into the viral genome, and viral recombinants were selected for their thymidine kinase-deficient phenotype. The insertion of these fragments by homologous recombination was highly efficient in that all the viral clones isolated contained the inserted fragment at the expected location. The only fragments that promoted additional inversions of the viral genome were those spanning the junction between the L and S components. Furthermore, analysis of isomers formed by these recombinants indicates that the inversions occur only when sequences in the inserted fragment are in inverted orientation in relation to homologous sequences at the termini or at the authentic junction. PMID- 6253079 TI - DNA of Epstein-Barr virus VIII: B95-8, the previous prototype, is an unusual deletion derivative. AB - B95-8, an infectious mononucleosis-derived isolate of Epstein-Barr virus (EBV), is biologically and antigenically indistinguishable from other isolates of EBV and has been the prototype for previous studies of EBV DNA. The long unique region UL of the DNA of a Burkitt tumor isolate, W91, is 9 X 10(6) daltons longer than the UL of B95-8. The "additional DNA and the regions around it have been cloned from W91 and another Burkitt tumor isolate, AG876. The additional DNA is viral and not cellular, since W91 and AG876 have almost identical additional DNA, and there is no detectable homology to human lymphocyte DNA. The insertion site of the additional DNA is within the 0.96 X 10(6) dalton Hinf 1 fragment of B95-8 Bam Hl l. After infection and transformation of five cell lines B95-8 did not pick up additional DNA in this region. Hybridization of labeled DNAs from three EBV-infected cell lines derived from patients with infectious mononucleosis to blots of fragments of the additional DNA indicates that these sequences are present in American as well as in African virus. B95-8 is therefore an unusual deletion derivative. A newly discovered feature of EBV DNAs is that sequences which map near the left end of UL have homology to part of the additional DNA. PMID- 6253080 TI - E. coli and M. luteus DNA topoisomerase I can catalyze catenation of decatenation of double-stranded DNA rings. AB - Escherichia coli and Micrococcus luteus DNA topoisomerase I are found to promote catenation of double-stranded DNA rings. At low DNA concentration dimeric catenanes are the major catenated products; at high DNA concentration or when spermidine is present, catenanes containing more than two rings are formed. There is no requirement of extensive sequence homology between the conponent rings forming a catenane; dimeric catenanes between Pseudomonas phage PM2 DNA and E. coli plasmid pBR322 are readily formed. The formation of a dimeric catenane by these type I topoisomerases, however, requires the presence of at least one preexisting single-chain scission in one of the two component rings. This is in contrast to the cases with the type II DNA topoisomerases which can form catenanes made of covalently closed rings only. The catenanes formed by the type I enzymes can be unlinked by the same enzymes, or by DNA gyrase, a type II enzyme, upon dilution of the isolated catenanes. The catenation and decatenation of duplex DNA rings adds a fourth type of reaction promoted by these type I DNA topoisomerases to the three reported previously: relaxation of superhelical DNA, interconversion between single-stranded DNA rings with and without knots and the intertwining of single-stranded DNA rings of complementary sequences into a covalently closed duplex ring with a high linking number. All four topoisomerization reactions involve the crossing of one DNA strand through a transient break of another DNA strand. The new reaction reported here suggests that such a crossover event might not require pairing of complementary nucleotide sequences. PMID- 6253081 TI - Homothallic conversions of yeast mating-type genes occur by intrachromosomal recombination. AB - The switching of yeast mating-type alleles involves a transposition of a copy of a sequence from HML or HMR to replace the sequences at MAT. Using diploid strains of yeast we have discovered that about 1% of the homothalic conversions of MAT alleles are accompanied by large intrachromosomal rearrangements. These rearrangements are highly specific fusions of part of MAT either with HMR (to produce a deficiency ring chromosome). We conclude that the mechanism of MAT conversions involves a highly specific pairing between the homologous sequences at MAT and the donor genes HML or HMR followed by a specialized gene conversion event, in which the original allele is replaced by a sequence copied from HMR or HML. At about a 1% frequency conversion of the MAT locus is accompanied by a reciprocal recombination event that results in an intrachromosomal deletion. This same preferential pairing is reflected in a high frequency (> 10(-3)) of site specific mitotic recombination between MAT alleles on differenat chromosomes. A gene conversion model also allows us to explain the "illegal" transpositions of MAT alleles to HMR or HML that occur when normal excision of MAT is prevented. PMID- 6253082 TI - Evidence for a physical interaction between the transposed and the substituted sequences during mating type gene transposition in yeast. AB - Mating type switches in the yeast Saccharomyces cerevisiae occur by transposition of a replica of the "source" unexpressed loci HML and HMR to the mating type locus (MAT). The incoming information replaces previously expressed DNA, resulting in an interconversion of MAT alleles. A strain of genotype HML alpha/HML alpha MAT alpha/mata-missense HMR alpha/hmra-nonsense HO/ho generates cells with the genotype HML alpha/HML alpha MAT alpha/MAT a HMR alpha/hmra nonsense HO/ho; that is, wild-type MATa+ recombinants are produced efficiently by a strain in which the incoming a information and the resident mata allele bear different mutations. Production of the wild-type MATa recombinants requires the homothallism (switching) function, and the incoming a information and the resident mata allele must bear different mutations. This result is consistent with the formation of a heteroduplex between the incoming and the outgoing DNA at MAT. Thus a process of unidirectional gene conversion as a mechanism for mating type gene transposition is favored. A molecular model based on a single-strand transfer is proposed. Results also favor the idea that the direction of switching is controlled by cell's mating phenotype rather than by the genetic content of MAT. PMID- 6253083 TI - Genetic and physical linkage of exogenous sequences in transformed cells. AB - The calcium phosphate precipitation method of Graham and van der Eb (1973) is an efficent means of introducing DNA into culturaed animal cells. Cells which incorporate one selectable marker are also likely to incorporate one selectable marker are also likely to incorporate sequences from the carrier DNA. Both selected and unselected markers are found integrated in the high molecular weight nuclear DNA of the host. In the present study, we demonstrate that exogenously acquired sequences are gentically linked, segregating and amplifying coordinately, and that their flanking sequences derive primarily from the carrier species rather than the host species. Based on these results, we propose that, upon transformation, the host cell ligates incorporated DNA into a large concatameric structure which may at times be as large as 2000 kilobases. From blotting data alone we cannot determine whether this structure is chromosomal or extrachromosomal in location. PMID- 6253084 TI - Association of polyoma T antigen and DNA with the nuclear matrix from lytically infected 3T6 cells. AB - Nuclear matrix prepared from mouse 3T6 cells lytically infected with polyoma virus retained significant amounts of the 100K T antigen and intact viral genomes. Bound T antigen was resistant to the extraction by high salt (2 M NaCl), detergent (1% Triton X-100) and exhaustive DNAase treatment. Only conditions sufficient to disrupt the integrity of the matrix itself solubilized the matrix T antigen. During the time period of 16-30 hr after infection, both the accumulation (in microgram) and the incorporation of 35S-methionine into T antigen increased steadily in cell extracts to a peak at 26 hr and then declined. In contrast, the amount of labeled T antigen retained by the matrix was relatively constant over the same time period. Matrix-bound T antigen was more highly phosphorylated and newly synthesized compared with the extractable T antigen. Viral DNA steadily accumulates in nuclei and on the matrix from 18 to 30 hr after infection. The fraction of viral DNA retained by the matrix was greatest early in infection (25% at 16 hr), declining to less than 10% by 24 hr. These data are consistent with the existence of a fixed (and limited) number of sites for T antigen (more highly phosphorylated) on the matrix and implicate the nuclear matrix as a site of viral DNA replication and possibly encapsidation. PMID- 6253085 TI - Preferred DNA sites are involved in the arrest and initiation of DNA synthesis during replication of SV40 DNA. AB - Previous analysis of simian virus 40 (SV40) DNA replication revealed a 2-4 fold excess of DNA molecules that were 90 +/- 2% replicated, demonstrating that replication forks accumulate near the termination site. To determine whether replication is arrested at specific DNA sites, forks were located on the SV40 genome by specifically 32P labelling 3' ends of nascent DNA on purified replicating SV40 DNA, isolating the longest 32P-DNA chains, annealing them to SV40 DNA and then digesting them with a restriction endonuclease that cut near the terminatin site. 32P-DNA fragments of several discrete lengths were released, demonstrating that replication forks on native chromosomes were arrested at preferred sites on the DNA. Most forks were arrested when bidirectional DNA replication was 91% completed, and the two forks were separated by about 470 bp of unreplicated DNA centered at the expected termination site. Forks were also arrested at other locations such that the center of the termination region defined by DNA arrest sites varied by +/- 450 bp. Electron microscopic analysis of replicating DNA suggested that such variation may result from asynchronous arrival of some replication forks. Analysis of 5' end-labeled nascent DNA demonstrated that initiation of Okazaki fragments was also promoted at preferred DNA sites (about 100-120 per genome). Thus specific DNA sequences appear to be utilized throughout DNA replication, not just at the origin. PMID- 6253086 TI - T-Cell regulation of B-lymphoblastoid cell line function. PMID- 6253087 TI - Suppression of lymphokine production. I. Macrophage-mediated inhibition of MIF production. PMID- 6253088 TI - Benzo[a]pyrene metabolism in cells productively infected with simian virus 40. AB - The metabolism of benzo[a]pyrene (BP) by cell cultures and cell-free extracts of the monkey kidney cell line CV-1 was studied in uninfected and Simian virus 40 (SV40) infected cells. Metabolites formed were separated by high-pressure liquid chromatography (HPLC) and quantified by liquid scintillation techniques. The profiles metabolites formed by uninfected and SV40 infected cells were similar except that SV40 infected cell cultures metabolized BP at an increased rate relative to uninfected cells. In addition, SV40 infected cell cultures and cell free extracts produced an unknown compound which eluted between the 3 hydroxybenzo[a]pyrene and BP fractions. This material does not have a retention time characteristic of any of the known metabolites of BP. Labelled BP and/or its metabolites were bound to the viral DNA and histone components of intracellular viral minichromosomes as well as the viral DNA and proteins of mature virions. PMID- 6253089 TI - Acute effects of two melanocytolytic agents, hydroquinone and beta mercaptoethanolamine, upon tyrosinase activity and cyclic nucleotide levels in murine melanomas. AB - The acute in vitro actions of two potent melanocytolytic agents, hydroquinone (HQ) and beta-mercaptoethanolamine (MEA), were determined in the B-16, Cloudman S 91 and Harding-Passey (HP) murine melanomas grown in vivo. Drug treated melanoma dice (5--480 min) were analyzed for tyrosinase activity and cyclic nucleotide levels (cAMP, cGMP). HQ and MEA effects on tyrosinase activity are complex and vary with tumor type, duration of treatment and agent tested. MEA or HQ inhibited B-16 tyrosinase activity. With combined drug therapy, low concentrations of MEA plus HQ stimulate B-16 tyrosinase activity while high concentrations of the drugs have little effect on enzymatic activity. MEA depresses tyrosinase activity while HQ elevates enzymatic activity in the S-19 melanoma. Both high and low concentrations of the combined drugs (MEA plus HQ) elicit the same response, stimulation at 10 min followed by continued depression of tyrosinase activity for the remainder of the 4 h study period. MEA initially stimulates HP tyrosinase activity followed by depression of enzymic activity. In contrast, HQ initially depresses HP tyrosinase activity followed by stimulation of enzyme activity. In combination the drugs inhibit HP tyrosinase activity. The effects of MEA and/or HQ on murine melanoma cyclic nucleotide levels are equally complex. MEA or HQ elevate cAMP and cGMP levels in all three tumors with the exception of S-91 cGMP levels which are not altered. In combination the drugs increase cyclic nucleotide levels in each of the three tumor types but at different times. No correlation is present between cyclic nucleotide levels and tyrosinase activity. Thus, the action of increased cyclic nucleotide levels in melanogenesis can not be separated from the direct actions of MEA and HQ upon melanogenesis. The divergent effects of MEA and/or HQ on tyrosinase activity and cyclic nucleotide levels in these melanomas are not correlated with the known in vivo melanocytolytic activity of these drugs. Thus, these parameters appear to be inadequate indicators of melanoma cell viability in chemotherapeutic screening of drugs effective in destroying malignant melanoma. PMID- 6253090 TI - Mechanism of stimulation of pinocytosis by trypan blue. AB - Trypan blue at 50 microgram/ml stimulates the pinocytic uptake of 125I-labelled PVP, but not of colloidal 198Au or formaldehyde-denatured 125I-labelled bovine serum albumin, by the 17.5-day rat visceral yolk sac incubated in vitro. Neither Trypan blue nor a combination of the dye with 125I-labelled PVP stimulated the rate of pinocytosis of liquid by the tissue. Trypan blue itself was shown to enter the yolk-sac cells by adsorptive pinocytosis. It is proposed that an interaction between Trypan blue and 125I-labelled PVP enables the latter substrate to enter the cells adsorptively by so-called 'piggy-back' pinocytosis. PMID- 6253091 TI - Modulation of the mitotic action of ethylene dibromide. AB - Refeeding rats treated with a single high dose of ethylene dibromide (1,2 dibromoethane, EDB) induced liver DNA synthesis. The peak of DNA synthesis, as measured by [methyl-3H]thymidine incorporation was attained after 24 h in refed rats and at 48 h in fasted ones. Fasting enhances the EDB action leading to liver cell necrosis, as shown by elevation of serum enzymes' activities, glutamic pyruvic transaminase (GPT) and sorbital dehydrogenase (SDH). A low dose of EDB administered during 2 and 3 weeks slightly enhanced the liver DNA synthesis and elevated the activity of serum enzymes. Phenobarbitone (PB) treatment of rats together with low dose of EDB during 2 weeks prevented the enzyme activity elevation and attenuated the DNA synthesis. Diethyldithiocarbamate (DDC) pretreatment potentiated the DNA synthesis in fed rats after both a small dose of EDB for 2 weeks and after a single high-dose treatment. In DDC pretreated rats, the high single dose of EDB caused biochemical perturbations in serum and liver representative of liver cell necrosis; changes in serum enzymes' activities also were noticed as early as 2 h after EDB toxication. The possible function of modulators on the mitogenic or the necrogenic action of EDB is discussed. PMID- 6253092 TI - [A study of ultrastructure of pituitary adenomas--a preliminary report of 10 cases examined with light and electron microscope (author's transl)]. PMID- 6253093 TI - [Detection of EB virus nuclear antigen (EBNA) by anticomplement immunoenzymatic method (author's transl)]. PMID- 6253094 TI - Misonidazole peripheral neuropathy: its relationship to plasma concentration and other drugs. AB - The data from 44 patients with documented glioblastoma who received 1.5 g/m2 of misonidazole twice weekly in conjunction with whole brain radiotherapy (total dose 6000 rad) was analyzed for factors associated with the development of peripheral neuropathy. The average total cumulative dose of misonidazole was 16.9 g/m2 and mild to moderate reversible peripheral neuropathy developed in 18% of patients. Peripheral neuropathy was positively associated with: 1) evidence of residual misonidazole in pretreatment plasma samples (> 10 microgram/ml), 2) elevated plasma concentrations of misonidazole on the day following treatment (> 25% of 4-hour plasma concentration), and 3) a prolonged plasma half-life (an average of 25% greater in patients developing peripheral neuropathy). The use of corticosteriods was negatively associated with the development of peripheral neuropathy and appeared to confer some protection. Age, sex, total dose of misonidazole, 4-hour plasma concentration (namely, at the time of radiotherapy), or the receipt of phenytoin or barbiturates was not related to the development of peripheral neuropathy. Monitoring of plasma misonidazole concentrations during treatment in conjunction with careful examination of the patient may result in a reduction of the incidence or severity of peripheral neuropathy. PMID- 6253095 TI - Results of the National Wilms' Tumor Study: Treatment response in misclassified patients. AB - This report evaluates the outcome in patients treated in accord with protocol requirements of the National Wilms' Tumor Study who were assigned incorrectly to any of several clinical groups because of mistaken initial assessments of the extent of disease. A significant difference in response was found between patients correctly staged Group I and those of higher stages incorrectly placed in Group I. This observation emphasizes the need for careful staging, and for "upstaging" in doubtful Group I patients. PMID- 6253096 TI - Tissue distribution and retention of 5-thio-D-glucose in animal tumor models. AB - 5-Thio-D-glucose (5-TDG) has demonstrated potential as a radiation sensitizer for hypoxic cells growing in monolayer culture and as multicell spheroids. We have studied the biodistribution and pharmacokinetics of radiolabeled (35S or 3H) 5 TDG prior to utilizing this bioisotere of D-glucose for radiation sensitization studies in vivo. At all times after administration, 5-TDG achieved higher tissue levels of radioactivity in hamster pancreatic tumors of ductal and acinar cell origin than in the normal pancreas. By 2 hours after intravenous injection, the duct tumor activity concentration exceeded that of any other tissue; a similar situation obtained after 4 hours in the acinar tumor model. However, the functioning insulinoma model exhibited similar radioactivity uptake and kinetics as did normal pancreas. In all models, metastases behaved similarly to the primary transplanted tumor in terms of uptake and retention of radioactivity. Addition of carrier 5-TDG appeared to abrogate much of the selective uptake of label into tumor relative to normal tissue, in terms of % dose/g tissue, but the total uptake into tumor was greater. The drug is rapidly excreted in the urine and the nature of this excretion was examined. Retention of activity in normal lung tissue was similar to that of pancreatic tumors and prompted a study of uptake into Lewis lung carcinoma. Again, tumor uptake in % dose/g approximated uptake into normal lung tissue, but total uptake into tumor was greater. These studies provided the basis for initiation of in vivo studies of potential cytotoxic and radiation-potentiating activity of 5-TDG. PMID- 6253097 TI - Rationale for initial clinical trials and future development of radioprotectors. AB - Over the past two decades a number of chemical radioprotectors have been developed which, although toxic, appear to be usable in clinically relevant doses. Because of differences in blood flow, radiochemical action in hypoxic cells, and active concentration in certain normal tissues, these compounds exhibit differential protection of normal tissue versus tumor. The best, currently available protector, WR-2721, is active in skin, intestine, marrow, mucosa, and salivary glands with lesser activity in kidney and lung and none in brain. Clinical trials have been designed in the Radiation Therapy Oncology Group based on this knowledge. Phase I studies involve patients requiring palliative radiotherapy for tumors located in or adjacent to tissues which are known to be protected. These studies use excalating doses of WR-2721, starting at 50 mg/m2 and will determine the maximum tolerated dose of drug, first as single doses and then as 1X, 3X, and 5X weekly for 3 and 6 weeks. Concomitant radiotherapy is given and normal tissue response at conventionl doses observed. Phase II studies will be site specific based on phase I results and doses. They will be radiation dose ranging studies designed to determine the maximum acceptable radiation dose at each site with WR-2721 protection. These new, higher doses will then be compared to conventional radiotherapy without protector, seeking increased tumor control in phase III studies. WR-2721 is not the ideal sensitizer since it does not protect all normal tissues. It is particularly important to develop compounds which can protect the brain, spinal cord, and lung. A large effort in new drug development will be justified if an improved therapeutic ratio is observed with WR-2721. PMID- 6253098 TI - Clinical experience with misonidazole: high dose fractions versus daily low doses. AB - In April 1976 clinical experience with misonidazole began at the University Clinic for Radiotherapy and Radiobiology of Vienna. Initially the drug was given mainly in four to six divided large doses ranging from 50 to 80 mg/kg (2.1-3.1 g/m2). Since October 1977 daily low doses in the range of 1-2g (0.45-1.3 g/m2) were used. So far over 100 patients with advanced tumor stages have been under investigation. Serum levels for the different treatment schedules are reviewed and sensitizer enhancement ratios larger than 1.3 may be expected even with daily low doses of misonidazole. Neurological side effects are analyzed and related to the cumulative dose (in g/m2) and overall treatment time. Depending on the overall time of drug administration the total dose of misonidazole can be adjusted to avoid undersirable side effects. It is our impression that normal tissue reactions are unchanged by the use of misonidazole. Preliminary results of a randomized clinical trial in patients with high-grade astrocytomas appear to be favorable for the sensitizer group. Als some impressive clinical results were seen in patients when using daily low doses of misonidazole. PMID- 6253100 TI - Antiemetics for patients treated with antitumor chemotherapy. AB - The clinical efficacy of antiemetic drugs was tested in cancer patients who were given a placebo and two antiemetic drugs alone and in combination according to random sequences. The method of investigation allowed assessment of the antiemetic effect and side effects of each drug or combination of drugs using a minimum number of patients. The trial design takes into account carry-over effects and biased selection and is potentially useful in the study of drug side effects. Fifteen patients received cyclizine, metoclopramide, cyclizine and metoclopramide, or placebo in a random sequence without evidence that the drugs tested were better than the placebo. A combination of Nabilone and metoclopramide was used in an unrandomized pilot study (prior to the withdrawal of Nabilone from clinical use); these patients recorded better scores for nausea and vomiting and patient acceptability than those in the randomized study. Present antiemetics remain inadequate and although cannabinol derivatives show an improved antiemetic effect, they cause moderate side effects themselves. PMID- 6253099 TI - Combined modality treatment of localized small-cell lung carcinoma. A randomized prospective study of the Southeastern Cancer Study Group. AB - Seventy patients with small-cell lung carcinoma limited to the thorax +/- ipsilateral supraclavicular lymph nodes were randomized to either of two study arms: 33 patients received radiation therapy (RT) alone consisting of 4500 rads in 5-6 weeks to primary tumor and regional lymph nodes, and 3500 rads in 2 1/2 weeks to brain as prophylaxis; 37 patients received, in addition to the RT above, chemotherapy (CT) with cyclophosphamide (500 mg/m2), Adriamycin (50 mg/m2), and DTIC (250 mg/m2) every 3 weeks given in two cycles before RT and seven cycles post-RT. Patients receiving RT alone who showed recurrence were crossed over to receive CT as above. Of 23 patients receiving RT alone who were evaluable 17 or 74% were responders; seven of these responses were complete (30%). On the RT and CT arm, of 24 evaluable cases, the response rate was 75%, of which 12 (50%) were complete. The median duration of disease-free survival of patients receiving RT + CT was 27 weeks, which ws superior to that of patients receiving RT alone (9.9 weeks, p = 0.019). The median survival of responders was essentially the same on both treatment arms; RT + CT, 47.7 weeks vs. RT alone, 50 weeks (p = N.S.). PMID- 6253101 TI - [The role of erionite (zeolite) in pulmonary mesothelioma]. PMID- 6253102 TI - [Inhibition of the 3' to 5' exonuclease activity of the DNA polymerase I of Escherichia coli by deoxyribonucleotides]. AB - The 3' a 5' exonuclease activity of E. coli DNA-polymerase I is inhibited by nucleotides and deoxynucleotides at concentrations (< 1 mM) where polymerase activity is not affected. This inhibitory effect depends on the nature of the excised deoxynucleotide, excision of purines being much less inhibited than that of pyrimidines. It does not depend on the purine or pyrimidine nature of the inhibitor. PMID- 6253103 TI - [5-Bromodeoxyuridine augmentation of the expression, on chick embryo fibroblasts of a cellular antigen present on avian oncoviruses]. AB - Treatment of Chick embryo fibroblasts (CEF) with 5-bromodeoxyuridine considerably increases the expression on the cell membrane of a cellular antigen related to an antigen specific to Chick embryo erythrocytes, present on the envelope of avian sarcoma oncoviruses produced by CEF. PMID- 6253104 TI - [Stress responses of the ACTH-corticosterone and LH-testosterone systems in male rats given naloxone]. AB - A single injection of naloxone (1 mg/kg s. c.) increased plasma baseline levels by 6 times for ACTH, 17 times for corticosterone, 3 times for LH and 2 times for testosterone. A concomitant ether-stress induced a further 6 fold increment in ACTH and an additional 2 fold increment in corticosterone, both hormones attaining their similar levels to those after ether-stress alone. On the other hand no further increment was observed for LH and testosterone, which actually were more stimulated by naloxone than by stress alone. The tonic inhibition exerted by endogenous opiates on ACTH and LH appears, therefore, to interfere with stress in a different way for the two neuroendocrine systems considered. PMID- 6253105 TI - Automated "Gamma-flo" radioimmunoassay of urinary cyclic AMP. AB - The "Gammaflow" automated assay concept of Brooker et al. (Science 194:270, 1976) has been adapted to the assay for urinary cyclic AMP in patients' samples on the now commercially available Squibb Gamma-FloTM system, a totally automated continuous-flow immunoassay instrument. The instrument aspirates the unknown sample, combines it with radioligand and specific antiserum, incubates the mixture, separates antibody-bound radioligand from free radioligand, counts the radioactivity of the bound ligand, computes the standard curve, and determines subsequent unknown samples by comparison to the standard curve. The urinary cyclic AMP assay we report here is rapid, accurate, and concentrations of cyclic AMP as low as 15 nmol/L can be detected. The assays, which can be done at 60 determinations per hour, are accurate at all dilutions of urine tested and inter assay (day-to-day) CVs were 3.9% at the midpoint of the standard curve (B/B0 = 0.49). PMID- 6253106 TI - Spectrophotometry of angiotensin-converting enzyme in sarcoidosis. PMID- 6253107 TI - Immunohistochemical demonstration of luteinizing hormone-releasing factor-like material in human syncytiotrophoblast and trophoblastic tumours. AB - Luteinizing hormone-releasing factor (LRF)-like immunoreactivity was demonstrated by a three layer bridge immunoperoxidase technique in the syncytiotrophoblast of early human placenta, hydatidiform mole and choriocarcinoma. Anti-LRF antiserum was prepared by immunizing rabbits with synthetic LRF coupled to bovine serum albumin (BSA). The immunoreactive site of LRF reacting with the antiserum resided between residues Tyr(5) and Gly(10)-NH2. Syncytiotrophoblast cells of the normal placenta from the first half of pregnancy and trophoblastic tumours, showed staining with anti-LRF antiserum after solid phase immuno-adsorption with Sepharose-coupled BSA. Adjacent control sections showed no staining when prepared with anti-LRF antiserum after immunoadsorption with a Sepharose-coupled LRF-BSA conjugate. The findings of LRF-like material in the placenta prompted us to examine the effect of exogenous LRF on the circulating levels of placental proteins and protein hormones synthesized by the syncytiotrophoblast. Serum levels of chorionic gonadotrophin, pregnancy-specific beta-l-glycoprotein, placental protein five, and placental lactogen remain unaltered for 2 h after an intravenous bolus of LRF (100-300 micrograms) to ten pregnant volunteers admitted for legal abortion between 8 and 18 weeks of gestation. The significance of LRF like material for the endocrinology of the normal and malignant trophoblast remains to be elucidated. PMID- 6253108 TI - ACTH and related peptides. PMID- 6253110 TI - Neutrophil function studies in patients with elevated serum IgE levels and recurring Staphylococcus aureus infections. PMID- 6253109 TI - Pancreatic polypeptide. PMID- 6253111 TI - Familial multicentric non-chromaffin paragangliomas: a case report on a patient with glomus jugulare and bilateral carotid body tumours. PMID- 6253112 TI - Caries-inhibiting effect of a stannous fluoride silica gel dentifrice: a three year clinical study. PMID- 6253113 TI - Pre-operative radiotherapy and surgery in the treatment of oat cell carcinoma of the bronchus. AB - The results of treatment of 90 patients with operable oat cell carcinoma from 1966 to 1976 by low dose pre-operative cobalt radiotherapy and radical surgery are given. Forty-nine patients were given 1750 and 24 2500 cGy (rad), there being no survivors in this latter group. No explanation for this is put forward. Of the 73 patients undergoing radical surgery 11 (15%) were alive and well at four years. The organisation of a multicentre random trial to establish the value of this treatment is suggested. PMID- 6253114 TI - Hepatic plasma-membrane modifications in disease. PMID- 6253115 TI - The effect of captopril on blood pressure and angiotensins I, II and III in sodium-depleted dogs: problems associated with the measurement of angiotensin II after inhibition of converting enzyme. AB - 1. Changes in arterial blood pressure, blood angiotensin I, plasma angiotensin II and plasma angiotensin III were measured in conscious sodium-depleted dogs after infusion of captopril, an orally active inhibitor of converting enzyme. 2. Angiotensins II and III were measured after chromatography to remove angiotensin I, which increased in concentration after inhibition of converting enzyme and which interfered in the direct assay for angiotensin II. 3. Infusion of captopril at 20, 200, 2000 and 6000 microgram h-1 kg-1, each for 3 h, produced a rapid fall in blood pressure and in concentration of angiotensin II. Angiotensin II was undetectable at 6000 microgram h-1 kg-1 (mean pre-infusion value for all samples was 39 +/- SD 15 pmol/1, n = 14). 4. The percentage fall in blood pressure correlated with the percentage fall in plasma angiotensin II (r = 0.65, P < 0.001). 5. These results suggest that the initial fall in blood pressure may be mediated in part by the suppression of angiotensin II. 6. Blood angiotensin I concentration rose with each rate of infusion of drug to a maximum 16-fold increase at 6000 microgram h-1 kg-1 (26-416 pmol/l). The rise in angiotensin I was inversely related to the fall in angiotensin II (r = 0.68, P < 0.001). PMID- 6253116 TI - Human lung adrenoreceptors studied by radioligand binding. AB - 1. Direct radioligand-binding techniques have been used to characterize and quantify adrenoreceptors in human peripheral lung tissue removed at thoracotomy from ten patients, nine of whom had evidence of obstructive airways disease. 2. [3H]Dihydroalprenolol was used to characterize beta-adrenoreceptor sites and [3H]prazosin to identify alpha-adrenoreceptor sites. Binding of both ligands showed saturability, high affinity, rapid kinetics, reversibility and stereospecificity. The rank order of agonists and antagonists inhibiting specific binding correlated well with known physiological potencies. Specificity of [3H]dihydroalprenolol binding suggested that the population of lung beta adrenoreceptors is predominantly of the beta 2 subtype. PMID- 6253117 TI - Cyclic nucleotide excretion in human malignancies. AB - 1. Urinary cyclic nucleotide excretion was studied in 51 patients with malignant tumours and in 24 control subjects. 2. Adenosine 3':5'-cyclic monophosphate excretion was normal in patients with tumours. 3. Urinary excretion of guanosine 3':5'-cyclic monophosphate was significantly greater than normal in patients with lymphoid tumours (both sexes) and in male patients with myeloid tumours or malignant melanoma. 4. Guanosine 3':5'-cyclic monophosphate excretion was normal in patients with breast carcinoma or colonic adenocarcinoma. PMID- 6253118 TI - The metabolism of a physiological dose of radioactive cholecalciferol (vitamin D3) to its hydroxylated metabolites in man. AB - 1. The metabolism of an intravenous pulse-dose of 65 nmol (25 microgram) of double-isotope-labelled cholecalciferol has been studied in 28 individuals. The subjects comprised 19 with serum concentrations of 25-hydroxycalciferol (25 (OH)D) less than or equal to 25 nmol/l, of whom 12 had clinical osteomalacia, and nine with serum 25-(OH)D > 25 nmol/l (30-125 nmol/l). 2. The concentrations in serum of radioactive cholecalciferol, 25-hydroxycholecalciferol (25-(OH)D3) and the three dihydroxylated metabolites: 1,25-, 24,25- and 25,26 dihydroxycholecalciferol (1,25-(OH)2D3, 24,25-(OH)2D3 and 25,26-(OH)2D3) were measured for up to 10 days after the injection. 3. The temporal relationships between the formation of individual radioactive metabolites and factors apparently influencing their production are described and their molar concentrations in serum calculated. 4. Formation of radioactive 1,25-(OH)2D3 was detectable only in vitamin D-deficient subjects. Between individuals, its maximum serum concentration was correlated significantly and inversely with serum calcium but with not other measured variable. In the individual, concentrations of radioactive serum 1,25-(OH)2D3 varied directly with radioactive serum 25-(OH)D3. 5. The failure to detect formation of radioactive 1,25-(OH)2D3 in vitamin D replete subjects suggests that current estimates of the daily turnover of the hormone in the normal individual may be severalfold too high. 6. Radioactive 25,26-(OH)2D3 was produced rapidly by all subjects and in greater amounts by vitamin D-deficient individuals. Between subjects and in the individual its concentration in serum correlated only with the radioactive serum 25-(OH)D3. Production of this metabolite appeared to be unregulated and dependent solely on the concentration of its precursor. 7. In vitamin D-replete subjects, production of 24,25-(OH)2D3 was also apparently determined by precursor concentration. In vitamin D-depleted subjects, production of radioactive 24,25-(OH)2D3 was variably delayed for up to or more than 10 days. 8. There appeared to be a constraint on the quantitative hepatic production of 25-(OH)D which is not explained by simple feed-back inhibition. 9. If sterols other than 1,25-(OH)2D3 are required to initiate the mineralization of osteomalacic bone, after correction of vitamin D deficiency in man, 25-(OH)D3 and 25,26-(OH)2D3 are produced sufficiently rapidly to meet this hypothetical requirement, but not 24,25-(OH)2D3. PMID- 6253119 TI - Importance of the cyclic AMP concentration for the rate of lipolysis in human adipose tissue. AB - 1. The activation of lipolysis on incubation of human subcutaneous adipose tissue was examined in terms of the relationship between the release of glycerol and the concentration of tissue cyclic AMP. 2. A strong positive correlation was obtained between the maximum concentration of cyclic AMP and the rate of glycerol release in the presence of noradrenaline (r = 0.9), whereas, in the basal state, these two parameters were only weakly correlated (r = 0.45). 3. It appears that the noradrenaline-induced rate of lipolysis depends upon the maximal concentration of cyclic AMP that is present in human adipose tissue. PMID- 6253120 TI - Nuclear magnetic resonance--a 'magnetic eye' on metabolism. PMID- 6253121 TI - The influence of carbohydrate gelling agents on rat intestinal transport of monosaccharides and neutral amino acids in vitro. AB - 1. In the present investigation with rings of everted rat small intestine, carbohydrate gelling agents (plant polysaccharides) such as guaran, pectin, tragacanth, carubin and carrageenan were employed to study their direct effect on intestinal absorption of alpha-methyl-D-glucoside, D-galactose, L-leucine and L phenylalanine. 2. Inhibition was found to correlate with the viscosity of the incubation medium, a function only of the polysaccharide concentration, and was independent of other properties of the carbohydrate gelling agents. 3. Reversal of this inhibition was achieved either by washing the tissue free of polysaccharide or by raising tissue agitation. 4. Uptake kinetics in polysaccharide-containing solutions revealed a marked increase of the apparent Michaelis constant although the maximal transport capacity remained essentially unaltered. 5. Since there was no binding of the substrate by the polysaccharides under experimental conditions as judged by a membrane filtration technique, it is concluded that carbohydrate gelling agents may impair intestinal absorption by means of an increased unstirred layer resistance. PMID- 6253122 TI - Indomethacin increases leucocyte beta-adrenoreceptors in man. AB - 1. The effect of indomethacin, an inhibitor of prostaglandin synthesis, on number and sensitivity of alpha- and beta-adrenoreceptors was studied in normal healthy volunteer subjects. 2. The subjects were studied under metabolic conditions. To achieve inhibition of prostaglandin synthesis indomethacin (2 mg day-1 kg-1) was given orally for 7 days. This dose decreased urinary excretion of prostaglandin E like immunoreactivity by 70%. 3. The number or alpha-adrenoreceptors was measured by the specific binding of [3H]dihydroergocryptine to platelet membranes and that of beta-adrenoreceptors by the binding of [3H]dihydroalprenolol to leucocyte membranes. 4. The number of alpha-adrenoreceptors did not change with indomethacin, nor did basal, prostaglandin E1- or noradrenaline-stimulated cyclic AMP production by platelet membranes. In contrast, the number of beta adrenoreceptors increased by 92%. Indomethacin did not affect, however, basal, 1 isoprenaline- or prostaglandin E1-stimulated cyclic AMP production in leucocyte membranes. 5. These results suggest that a reflex-mediated decrease in sympathetic discharge in response to an indomethacin-induced decrease in release of vasodilator prostaglandins may lead to an 'up-regulation' of beta adrenoreceptor sites. PMID- 6253123 TI - Catalytic properties of the SV40 large T antigen. PMID- 6253124 TI - Enzymatic activities associated with the SV40 large T antigen. PMID- 6253125 TI - DNA binding and sedimentation properties of SV40 T antigens synthesized in vivo and in vitro. PMID- 6253126 TI - Organization of T antigens in the polyoma virus genome. PMID- 6253127 TI - Is polyoma virus middle T antigen a protein kinase? PMID- 6253128 TI - Polyoma virus T antigens expressed in transformed cells: significance of middle T antigen in transformation. PMID- 6253129 TI - Purification and characterization of the SV40 F-gene protein. PMID- 6253130 TI - Phosphorylation of SV40 large T antigen. PMID- 6253131 TI - T antigens of SV40-transformed cells. PMID- 6253132 TI - Characterization of the complex between SV40 large T antigen and the 53K host protein in transformed mouse cells. PMID- 6253134 TI - SV40 17K protein is associated with two cellular proteins. PMID- 6253133 TI - T-antigen-associated proteins induced by SV40 transformation. PMID- 6253135 TI - Characterization of a murine cellular SV40 T antigen in SV40-transformed cells and uninfected embryonal carcinoma cells. PMID- 6253136 TI - SV40 T-antigen-related molecules on the surfaces of HeLa cells infected with adenovirus-2-SV40 hybrids and on SV40-transformed cells. PMID- 6253137 TI - SV40 transplantation antigen: relationship to SV40-specific proteins. PMID- 6253138 TI - Host antigens in the centriolar region are induced in SV40-infected TC7 cells: SV40 small-T-function requirement. PMID- 6253139 TI - Transformation induced by Epstein-Barr virus and the role of the nuclear antigen. PMID- 6253140 TI - The hr-t gene of polyoma virus. PMID- 6253141 TI - Early mutants of polyoma virus (dl8 and dl23) with altered transformation properties: is polyoma virus middle T antigen a transforming gene product? PMID- 6253142 TI - Deletion mutants of SV40 that affect the structure of viral tumor antigens. PMID- 6253143 TI - Origin-defective mutants of SV40. AB - We have described a new technique for the isolation and propagation of nonconditionally lethal mutants. We have used this method to generate mutants of SV40 that contain a defective origin of DNA replication. Using these mutants, we have established the following: (1) SV40 DNA replication and early transcription are functionally separate. (2) A functional viral origin of DNA replication is not necessary for the maintenance of transformation. (3) The lack of the origin of SV40 DNA replication does not affect the efficiency of transformation when nonpermissive cells are transfected by DNA using the calcium technique. PMID- 6253144 TI - Lytic infection of teratocarcinoma cells by polyoma virus mutants. PMID- 6253146 TI - Roles of the T antigens in transformation by SV40. PMID- 6253145 TI - SV40 mutant tsA1499 is heat-sensitive for lytic growth but generates cold sensitive rat-cell transformants. PMID- 6253147 TI - Requirement for the large T and small T proteins of SV40 in the maintenance of the transformed state. PMID- 6253148 TI - Host-virus interactions critical for cellular transformation by polyoma virus and SV40. PMID- 6253150 TI - SV40-induced somatic mutations: possible relevance to viral transformation. PMID- 6253149 TI - Viral and cellular control of the SV40-transformed phenotype. PMID- 6253151 TI - Structure and function of the transforming genes of human adenoviruses and SV40. PMID- 6253153 TI - Nucleotide sequences, integration, and transcription of the adenovirus-12 transforming genes. PMID- 6253154 TI - Viral DNA sequences in adenovirus-transformed cells. PMID- 6253152 TI - Regulation of SV40 gene expression through RNA splicing. PMID- 6253155 TI - A third splice site in SV40 early mRNA. PMID- 6253156 TI - Selectivity in integration sites of adenoviral DNA. PMID- 6253157 TI - Methylation of integrated viral DNA sequences in hamster cells transformed by adenovirus 12. AB - Data have been presented which demonstrate that the Ad12 DNA sequences integrated into the DNA of four lines of Ad12-transformed hamster cells are extensively methylated. Methylation in mammalian-cell DNA presumably occurs at 5'-CCGG-3' sequences mainly at the internal C residue. The majority, though not all, of the 5'-CCGG-3' sequences present in integrated Ad12 DNA are methylated. Further experiments will be required to elucidate the functional significance of the methylation of integrated Ad12 DNA. Ad12 DNA isolated from purified virions is not methylated to any significant extent. Recent results indicate that segments of the integrated viral DNA, which are expressed into mRNA in transformed cells, are undermethylated, whereas segments that are not expressed are extensively methylated. PMID- 6253158 TI - Analysis of the sites of integration of viral DNA sequences in rat cells transformed by adenovirus 2 or SV40. PMID- 6253159 TI - Tumorigenicity of polyoma virus in hamsters. PMID- 6253160 TI - Organization and expression of integrated polyoma virus DNA sequences in transformed rodent cells. PMID- 6253161 TI - Monkey cells transformed by SV40 DNA fragments: flat revertants synthesize large and small T antigens. PMID- 6253162 TI - Integration and excision of polyoma virus genomes. PMID- 6253163 TI - Rapid detection, isolation, and amplification of host-substituted SV40 variants. PMID- 6253164 TI - Morphological transformation by DNA fragments of human herpesviruses: evidence for two distinct transforming regions in herpes simplex virus types 1 and 2 and lack of correlation with biochemical transfer of the thymidine kinase gene. PMID- 6253165 TI - Comparison of polyoma virus transcription in productively infected mouse cells and transformed rodent cell lines. PMID- 6253166 TI - Sarcoma growth factor: specific binding to and elution from membrane receptors for epidermal growth factor. PMID- 6253167 TI - Regulation of plasminogen activator synthesis in chick embryo fibroblasts infected with avian retroviruses. PMID- 6253168 TI - SV40 and cellular gene expression in the maintenance of the tumorigenic syndrome. PMID- 6253169 TI - Expression of transformation in cell hybrids: analysis of a revertant of SVT2. PMID- 6253170 TI - Tumor formation by transformed cells in nude mice. PMID- 6253171 TI - Monoclonal antibodies: detection of transformation-related antigens. PMID- 6253172 TI - Transcription of SV40 DNA in transformed rat cells. PMID- 6253173 TI - Expression of transforming viral genes in semipermissive cells transformed by SV40 or adenovirus type 2 to type 5. PMID- 6253174 TI - Transforming genes of DNA tumor viruses. PMID- 6253175 TI - Transformation-defective, temperature-sensitive mutants of Rous sarcoma virus have a reversibly defective src-gene product. PMID- 6253176 TI - Localization of pp60src within normal rat kidney cells infected with temperature sensitive mutants (T-class) of Rous sarcoma virus. PMID- 6253178 TI - Isolation of a glucose transport system from normal chicken fibroblasts and from chicken fibroblasts transformed by Rous sarcoma virus. PMID- 6253177 TI - Genetic and biochemical approaches to analyzing transformation by Rous sarcoma virus. PMID- 6253179 TI - Growth-related alterations induced in chick embryo fibroblasts by src-gene deletion mutants of the Schmidt-Ruppin strain of Rous sarcoma virus. AB - Certain tdSRD viruses induce multilayered cell foci, agar colony formation, and increased density of cellular populations in line-15 chick embryo fibroblasts. These alterations in cellular growth properties are distinct from oncogenic transformation. Available evidence favors the idea that transformation-defective focus formation is caused by one or more of the replicative viral genes, but which of the three-gag, pol, or env-is involved, remains to be determined. PMID- 6253180 TI - Expression of the src-gene product, pp60src, in transformed and reverted mammalian cells infected with avian sarcoma virus. PMID- 6253181 TI - Factors affecting phenotypic reversion of rat cells transformed by avian sarcoma virus. PMID- 6253182 TI - Organization of endogenous and exogenous viral and linked nonviral sequences. PMID- 6253183 TI - Synthesis and integration of avian sarcoma virus DNA. AB - In this paper, we have presented data regarding the integration of viral DNA and the persistence of unintegrated viral DNA. We know that integration occurs with specificity with respect to the viral genome, and yet it remains to be established which, if any, of the unintegrated DS DNA species-either the linear or the covalently closed circular forms-is the immediate precursor to the DNA that does become integrated. The results of the present studies indicate that the viral DNA species that are able to persist in an unintegrated state may be transcribed to yield new virions. Furthermore, these species may not be intermediates as far as the integration pathway, but may instead be terminal products of a synthesis reaction that has proceeded beyond the point where integration normally occurs. Varmus et al. (1977) have shown that integration occurs only into newly replicated cellular DNA. Therefore, we would speculate that integration may occur by an interaction between a replication fork of the host cell DNA and an earlier, non-double-strand form of viral DNA. PMID- 6253184 TI - Avian endogenous proviral DNA: analysis of integrated ev 1 and a related gs- chf- provirus purified by molecular cloning. PMID- 6253185 TI - Ten genetic loci in the chicken that contain structural genes for endogenous avian leukosis viruses. AB - Our interpretation of the results presented here may be summarized as follows: (1) Endogenous viral genes can be located at any of a large number of sites in the chicken chromsome. (2) Different phenotypes of viral gene expression are observed, depending on the nature of the viral sequences at a given site and depending on whether the necessary sequence elements for expression are present. (3) Endogenous viral genes perform no essential function in the chicken. PMID- 6253186 TI - Transcriptional products and DNA structure of endogenous avian proviruses. PMID- 6253187 TI - Role of the C region in relative growth rates of endogenous and exogenous avian oncoviruses. PMID- 6253188 TI - Subgroup-E avian-leukosis-virus-associated disease in chickens. PMID- 6253189 TI - Structure and infectivity of integrated murine leukemia virus DNA. PMID- 6253190 TI - Construction and characterization of molecular clones containing integrated mouse mammary tumor virus sequences. PMID- 6253191 TI - Genomic location of mouse mammary tumor virus proviral DNA in normal mouse tissue and in mammary tumors. PMID- 6253192 TI - Transformation of NIH-3T3 mouse cells by avian retroviral DNAs. AB - NIH-3T3 cells were found to be transformable by RSV DNA in the absence of progeny virus production. Cells transformed by intact RSV DNAs contained rescuable RSV genomes that were integrated into cellular DNA and were colinear with unintegrated RSV DNA. NIH-3T3 cells were also transformable by subgenomic fragments of RSV DNA, synthesized in vitro or generated by restriction endonuclease digestion of intracellular RSV DNA. These cells did not contain rescuable RSV genomes but did contain RSV DNA fragments that efficiently induced transformation of NIH-3T3 cells in secondary transfection assays. Further analysis of the RSV DNA sequences present in these cells and transformation assays of defined fragments of RSV DNA may contribute to the elucidation of the sequences required for expression of the src gene of RSV. DNAs of the avian acute leukemia viruses MC29 and AEV also induced transformation of NIH-3T3 cells. The use of these cells as recipients may thus provide a system suitable for functional analysis of the transforming genes of avian leukemia viruses as well as sarcoma viruses. PMID- 6253193 TI - Transformation by Abelson murine leukemia virus: properties of the transformed cells. AB - Ab-MuLV transforms mouse 3T3 fibroblasts, macrophages, and lymphocytes, which have properties of immature cells in the B-lymphocyte differentiation pathway. Differences in expression of intracellular immunoglobulin and surface antigens the lymphoma lines suggest that more than one B-lymphocyte differentiation stage may be transformed, each of which must be before the B lymphocyte acquires cell surface immunoglobulin receptors for antigen and antigen sensitivity. The plasmacytomas induced by Ab-MuLV plus pristane tested thus far show no evidence of infection by Ab-MuLV. The transformation of these immunoglobulin-secreting cells may be due to causes other than the transforming elements of the Ab-MuLV genome. PMID- 6253195 TI - Three new types of viral oncogenes in defective avian leukemia viruses. I. Specific nucleotide sequences of cellular origin correlate with specific transformation. PMID- 6253194 TI - Cell-surface antigens of Abelson and Friend murine leukemia viruses and of hematopoietic differentiation. PMID- 6253196 TI - Three new types of viral oncogenes in defective avian leukemia viruses. II. Biological, genetic, and immunochemical evidence. PMID- 6253197 TI - Recombination in the avian oncoviruses as a model for the generation of defective transforming viruses. PMID- 6253198 TI - Progenitor-cell populations can be infected by RNA tumor viruses, but transformation is dependent on the expression of specific differentiated functions. PMID- 6253199 TI - Murine-leukemia-virus-related cell-surface antigens as serological markers of AKR ecotropic, xenotropic, and dualtropic viruses. PMID- 6253200 TI - Status of the association of mink cell focus-forming viruses with leukemogenesis. PMID- 6253201 TI - Analysis of the genomes of mink cell focus-inducing murine type-C viruses: a progress report. PMID- 6253202 TI - Murine leukemia virus env-gene expression in preleukemic thymocytes and leukemia cells of AKR strain mice. PMID- 6253203 TI - Evolution of oncogenic mouse type-C viruses in cell culture. PMID- 6253204 TI - T-lymphoma retroviral receptors and control of T-lymphoma cell proliferation. PMID- 6253205 TI - Summary: molecular biology of viral oncogenes. PMID- 6253206 TI - Organization of murine sarcoma virus genomes. PMID- 6253207 TI - Cellular origin of the transforming gene of Moloney murine sarcoma virus. PMID- 6253208 TI - Characterization of integrated Moloney Sarcoma proviruses and flanking host sequences cloned in bacteriophage lambda. PMID- 6253209 TI - Characterization of virus-specified proteins present in NRK cells infected with a temperature-sensitive transformation mutant of Moloney murine sarcoma virus. PMID- 6253210 TI - Comparative analysis of cellular and viral sequences related to sarcomagenic cell transformation. PMID- 6253211 TI - Transforming protein encoded by the cellular information of recovered avian sarcoma viruses. PMID- 6253212 TI - Correlation of transient accumulation of linear unintegrated viral DNA and transient cell killing by avian leukosis and reticuloendotheliosis viruses. PMID- 6253214 TI - Genetic structure of avian acute leukemia viruses. PMID- 6253213 TI - Isolation and characterization of proteins carrying the feline oncornavirus associated cell-membrane antigen. PMID- 6253215 TI - Analysis of RNA specific for the transforming agent of R-strain avian erythroblastosis virus. PMID- 6253216 TI - Characterization of the src gene of a Rous sarcoma virus mutant temperature sensitive for cell transformation. PMID- 6253217 TI - Structure and expression of the Abelson murine leukemia virus genome and its relationship to a normal cell gene. PMID- 6253219 TI - Characterization of Abelson murine leukemia virus isolates differing in P120 expression. PMID- 6253218 TI - A trans-acting protein kinase identified in cells transformed by Abelson murine leukemia virus. PMID- 6253220 TI - Mammalian RNA type-C transforming viruses: characterization of virus-coded polyproteins containing phosphorylated components with possible transforming functions. PMID- 6253221 TI - Moloney murine sarcoma virions contain subgenome-length mRNA-like molecules that direct the synthesis of sarcoma-specific polypeptides in vitro. PMID- 6253222 TI - Protein phosphorylation mediated by partially purified avian sarcoma virus transforming-gene product. PMID- 6253223 TI - Origin and function of avian retrovirus transforming genes. PMID- 6253224 TI - Studies on the structure and function of the avian sarcoma virus transforming gene product. AB - The protein kinase activity associated with pp60src of a mutant of RSV temperature sensitive for transformation was shown to be sixfold more labile than that of its wild-type parent at 45 degrees C when pp60src's synthesized in vitro were compared. Thus, a mutant that is temperature sensitive for transformation has a temperature-sensitive protein kinase activity. Analysis of the levels of protein kinase activity in immunoprecipitates from cells infected with four different temperature-sensitive mutants of RSV led to the surprising finding that two mutants had barely detectable levels of protein kinase activity even at the permissive temperature, whereas two others had levels of activity at the nonpremissive temperatures that were as great as 40% that of wild-type pp60src. Protein kinase activity of pp60src of NY68 was partially renatured when cells were shifted from 41 degrees C to 36 degrees C. This reactivation occurred in less than an hour and did not require protein synthesis. It was found that pp60src synthesized in vitro is phosphorylated. Finally, the methionine containing tryptic peptides of pp60sarc immunoprecipitated from uninfected chick cells were very similar to those of viral pp60src. PMID- 6253225 TI - In vitro synthesis and processing of Rous sarcoma virus src-gene products. PMID- 6253226 TI - Activities of the src-gene product of avian sarcoma virus. PMID- 6253227 TI - Comparison of protein kinase activities in normal cells and cells transformed by a temperature-sensitive mutant of avian sarcoma virus to those of cell-free viral translational products. PMID- 6253228 TI - F-actin inhibits protein kinase activity associated with the src-gene product. PMID- 6253229 TI - Transformation by Rous sarcoma virus: effects of src-gene expression on the synthesis and phosphorylation of cellular polypeptides. PMID- 6253230 TI - Expression of viral oncogenes in differentiating chick embryo neuroretinal cells infected with avian tumor viruses. PMID- 6253231 TI - Localization and characterization of the src-gene product of Rous sarcoma virus. PMID- 6253232 TI - Acceleration of desipramine-induced decrease of rat corticocerebral beta adrenergic receptors by yohimbine. PMID- 6253233 TI - Cotranslational and posttranslational processing of viral glycoproteins. PMID- 6253234 TI - Paget's disease of the breast. A subtle clinical presentation. AB - Paget's disease of the breast often presents with an underlying palpable breast mass. However, the absence of an underlying mass at the time of diagnosis is associated with improved survival rates. A case is presented emphasizing the importance of careful clinical and biopsy examination when the disorder presents with subtle clinical findings. PMID- 6253235 TI - Pneumocystis carinii pneumonitis in patients with lung cancer. AB - Pneumocystis carinii pneumonia was histologically documented in five patients with bronchogenic carcinoma. All patients had been treated with combination antineoplastic chemotherapy. Two patients received no corticosteroids, two received no chest radiotherapy, and one received neither radiotherapy nor corticosteroids. This suggests that as more patients with lung cancer are treated with intensive chemotherapy, pulmonary infection with P carinii may become an important differential diagnostic consideration in the presence of pulmonary infiltrates. PMID- 6253236 TI - Studies on new attenuated strains of type III live poliomyelitis vaccine. I. Development of a new type III attenuated poliovirus. PMID- 6253237 TI - Studies on new attenuated strains of type III live poliomyelitis vaccine. II. Field trials of Zhong III2 virus. PMID- 6253238 TI - Time-varying effects in mice and rats of several synthetic ACTH preparations. AB - Circadian stage-dependent effects characterize synthetic ACTH 1-17 preparation (HOE 433 = Synchrodyn 1-17), tested in mice and rats, with reference notably to corticosterone and aldosterone production in vitro and to the behavior of rhythms in these two corticoids as an aspect of the adrenal cortical pacemaker of the circadian system. The possibility to advance or delay the rhythm in serum corticosterone by ACTH 1-17 also is demonstrated, as is a differential behavior of the circadian rhythm in serum aldosterone. Differences in timing of circadian corticosterone and aldosterone responses also are described and await further scrutiny for ultradian and infradian (notably circannual) modulation. PMID- 6253239 TI - Synthetic adrenocorticotropin for optimizing murine circadian chronotolerance for adriamycin. AB - An attempt to pre-set the circadian rhythm in murine chronotolerance for adriamycin (ADR) given i.p. or i.v. with ACTH was performed in three studies. In CDF1 mice standardized in LD12:12, it was demonstrated that 1) the circadian rhythm in murine chronotolerance for ADR exhibits a different timing depending upon whether the intravenous or intraperitoneal route is used for the administration of this anticancer agent; 2) ACTH or saline pretreatment does not enhance optimal circadian-stage-qualified ADR tolerance, whatever its route of injection, with any of the circadian stages and schedules explored; 3) near optimal tolerance can be achieved by a fixed 'best' interval (among those investigated) between ACTH and ADR, irrespective of circadian stage. Tolerance equivalent to optimal circadian-stage-qualified ADR tolerance results from the administration of ACTH 1-17 (HOE433 = Synchrodyn) 24 hours before ADR injection; 4) and acrophase advance of over 6 hours of the tolerance rhythm results from ACTH 1-17 administration at 6 HALO. The acrophase changes do not directly account for an optimal ADR tolerance at a fixed interval of 24 hours after ACTH 1-17. Thus, ACTH may be considered a potential relative chronizer of murine chronotolerance for ADR. PMID- 6253240 TI - Plasma catecholamines and cardiac, renal and peripheral vascular adrenoceptor mediated responses in different age groups of normal and hypertensive subjects. AB - The role of the sympathetic nervous system in cardiac, renal and peripheral vascular adrenoceptor-mediated responses was investigated in patients with essential hypertension and age-matched normotensive subjects. Regardless of age plasma adrenaline was significantly higher in hypertensive when compared with normotensive subjects. This suggests a sympatho-adrenal factor in essential hypertension. Plasma noradrenaline tended to increase with age but its similarity between normotensive and hypertensive subjects points to similar postganglionic neural activity and/or similar overflow of noradrenaline into the circulation. On the other hand, beta-adrenoceptor-mediated tachycardia in response to exercise and intravenous isoproterenol as well as the forearm vasodilator response to intraarterial isoproterenol decreased in normal subjects with older age. In hypertensives this age-dependent beta-receptor-related effect tends to be enhanced as judged from the greater reduction of cardiac isoproterenol sensitivity and the blunted renin response to exercise stimulation. The dilator response to alpha-adrenoceptor blockade with phentolamine was not different in both groups. Therefore a qualitative rather than quantitative derangement of sympathetic control of vascular resistance - in which beta-dilator effects are reduced and alpha-constrictor mechanisms prevail - may contribute to the maintenance of established hypertension. PMID- 6253241 TI - Angiotensin II and renal hypertension in dog, rat and man: effect of converting enzyme inhibition. AB - The role of the renin-angiotensin system in the pathogenesis of one-clip, two kidney hypertension has been studied in man, dog and rat. Particular attention has been paid to peripheral plasma concentrations of angiotensin II in different circumstances; angiotensin II infusion has been combined with radioimmunoassay to construct angiotensin II/blood pressure dose-response curves. The effect of converting enzyme inhibitors has been studied, precautions being taken to avoid obtaining falsely high values for plasma angiotensin II because of cross-reaction with angiotensin I in these circumstances. The initial phase of one-clip, two kidney hypertension is attributable to the direct pressor effect of the immediate rise in plasma angiotensin II. Subsequently, plasma angiotensin II is relatively lower, although blood pressure remains high. This upward resetting of the plasma angiotensin II/blood pressure relationship can be mimicked by infusing angiotensin II chronically at low dose. After reconstruction of a stenosed renal artery, or excision of a post-stenotic kidney, the angiotensin II/blood pressure relationship returns slowly to normal. In this second phase of one-clip, two kidney hypertension, the long-term administration of saralasin, or of converting enzyme inhibitor, can also return arterial pressure to normal; brief administration of these drugs is less effective or ineffective. The results are compatible with, although they do not conclusively establish, an important slow pressor action of the renin-angiotensin system in the second phase of one-clip, two-kidney hypertension. This provides a rational basis for the use of captopril clinically in this condition. PMID- 6253242 TI - The renin system and future trends in management of high blood pressure. AB - Recent research has shown that the renin-angiotensin-aldosterone system plays a role in maintaining or causing high blood pressure in the majority of patients and it has demonstrated that renin-sodium profiling defines this involvement. Plasma renin activity measurements reveal the degree of renin-mediated vasoconstriction supporting the blood pressure, and the urinary sodium value indicates the appropriateness of the renin activity to the volume status. Together with determination of serum potassium levels, this test is basic for screening and for definitive diagnosis of the surgically curable forms of renovascular and adrenocortical hypertension. For the remaining majority of patients with other forms of hypertension, renin profiling, used in the context of the vaso-constriction-volume analytical model, helps to reveal the relative participation of vasoconstriction and volume factors and it thereby guides simpler, more specific, and more predictable treatments using either antirenin or antivolume agents. In particular, renin profiling allows the physician to select those patients who should first receive a beta-blocker or a newer anti-renin drug instead of a diuretic. The vasoconstriction-volume analysis also can provide useful baseline information about the pace, severity, and prognosis of the disease in individual patients. For medical practice the new approach enables treatment with one drug instead of two for major subgroups, and the likelihood of more specific physiologic corrections. More research within this framework promises even better treatments as we near final solutions. PMID- 6253243 TI - Enhancement by diuretics of the antihypertensive action of long-term angiotensin converting enzyme blockade. AB - Thirty-nine patients with various types of hypertension were treated by chronic blockage of the angiotensin converting enzyme, i.e. by twice daily administration of captopril, 50 to 200 mg p.o. The blood pressure reduction observed 1 hour following administration of the inhibitor was directly related to the baseline plasma renin activity (r=- 0.67, p < 0.001). Whenever blockade of the renin system alone did not lower blood pressure to normal levels additional sodium subtraction brought it under control. With the renin system neutralized, blood pressure becomes exquisitely sensitive to changes in sodium balance. Diuretics seem to preserve optimal natriuretic efficacy despite blood pressure reduction, probably because aldosterone levels are reduced and renal blood flow increases. Blockade of the renin system together with individually tailored salt subtraction provides an attractive new approach to long-term treatment of clinical hypertension. PMID- 6253245 TI - Aldosterone-induced hypertension: effects of a kininase inhibitor. AB - A synthetic orally active angiotensin I converting enzyme inhibitor Captopril (Squibb), (D-2-methyl-3-mercaptopropanoyl-L-Proline), was administered to three groups of hypertensive animals. The animals were made hypertensive by uninephrectomy, daily injections of 5 ug/100 g body weight d-aldosterone (Sigma) in wheat germ oil and substitution of 0.9% NaCl for the drinking water. Captopril was given to pregnant and nonpregnant animals during the developmental phase of hypertension and to nonpregnant animals with established (4 weeks of treatment) hypertension. The agent attenuated the hypertension in both the pregnant and nonpregnant animals when given while hypertension was developing. Captopril was effective in reducing established aldosterone-NaCl hypertension to normotensive levels. PMID- 6253244 TI - Kinins and angiotensins. Angiotensin I converting enzyme (kininase II) in endothelial cells cultured from human pulmonary arteries and veins. AB - Human pulmonary endothelial cells were used to study the metabolism of angiotensin I and bradykinin by angiotensin I converting enzyme (kininase II; ACE). The endothelial cells cultured from pulmonary arteries and veins differed with respect to their enzyme activity and their surface structure, as viewed with scanning electron microscopy. Cells from adult pulmonary arteries had greater ACE activity than cells from either adult pulmonary veins or fetal pulmonary arteries. In addition, cells from adult pulmonary arteries exhibited more prominent surface projections than cells from veins or fetal pulmonary arteries. A brief exposure to trypsin decreased the ACE activity in cells from arteries but not in cells from veins. Possible the differences in ACE activity between these cells are related to their surface structures. PMID- 6253246 TI - [Dual control of liver disulfide reductase activity]. PMID- 6253247 TI - [Isolation and characteristics of the new site-specific endonuclease Eco RV]. PMID- 6253248 TI - [Development of positional asymmetry during pain, immobilization, and cold stress]. PMID- 6253249 TI - [Energy profile of the calcium channel in mollusk neuron membranes]. PMID- 6253250 TI - [Mechanism of action of the new calcium current blocker nifedipine (adalate, Bay 1040)]. PMID- 6253251 TI - [Reversible increase in the maximal potassium permeability of a nerve fiber membrane following formamide application]. PMID- 6253252 TI - [RecA+-independent formation of recombinant plasmids in strains of E. coli producing Eco RI restriction endonuclease]. PMID- 6253253 TI - [Demonstration of calcium channels in the somatic membrane of rat spinal ganglia neurons following intracellular dialysis with cyclic adenosine-3', 5' monophosphate]. PMID- 6253254 TI - [Outer retinal rod segment cyclic nucleotide phosphodiesterase; protein inhibitor separation, bimodal effect of GTP]. PMID- 6253255 TI - [Localization of R. SmaI restriction endonuclease recognition sites on the genetic map of T4 bacteriophage]. PMID- 6253256 TI - [Monochloroaniline breakdown via the meta cleavage in Alcaligenes faecalis]. PMID- 6253257 TI - [Photo-induced structural changes in the melanoprotein granules of pigmented epithelium]. PMID- 6253258 TI - [Synthetic ligands capable of "recognizing" DNA AT-sequences possessing a 2nd order axis of symmetry]. PMID- 6253259 TI - [Changes in DNA sensitivity to S1 nuclease in the process of aging and after the experimental action of a gerontologic protective agent]. PMID- 6253260 TI - [Above-average synthesis of anti-HAV by a booster effect after viral hepatitis A (author's transl)]. AB - Above-average high antibody titres without repeat illness were obtained in 31 persons who, after having recovered from viral hepatitis A had renewed contact with the hepatitis-A virus. The titre was five to thirty-fold above the level usually observed after the initial infection. The time of second or third infection appears to be decisive for the level of the titre rise, which is probably a booster effect. PMID- 6253261 TI - 19-nor analogs of adrenal steroids: mineralocorticoid and glucocorticoid receptor activity. AB - The effect of absence of the C-19 methyl group from five adrenal steroids has been studied in terms of their affinity for mineralocorticoid (MR) and glucocorticoid receptors (GR). In MR assays, 19-nordeoxycorticosterone and 19 norprogesterone showed 3-fold higher affinity for MR than did their respective parent steroids; 19-norcortisol had 1.5 times the affinity of cortisol for MR. In contrast, corticosterone and 19-nororticosterone showed equal affinity, and 19 noraldosterone showed less than 1% the MR activity of aldosterone. In GR assays, the absence of the C-19 methyl group from progesterone increased GR affinity 3 fold and deoxycorticosterone affinity 1.5-fold. In contrast, the other 19-nor steroids showed decreased affinity vis a vis their parent compounds (19 norcorticosterone, 30%; 19-norcortisol, 10%; 19-noraldosterone, < 1%). These findings suggest that while the 19-nor analogs of 11-deoxy steroids are consistently more active than their parent steroid, the 19-nor 11-oxygenated adrenal steroids show no predictable pattern of binding for MR or GR. PMID- 6253262 TI - Desensitization of primary cultures of adult rat liver parenchymal cells to stimulation of adenosine 3',5'-monophosphate production by glucagon and epinephrine. AB - The ability of glucagon or epinephrine to increase cAMP levels in primary monolayer cultures of adult rat liver parenchymal cells was markedly reduced to pretreatment of the cells with the same hormone. Induction of cAMP production by glucagon (2 X 10(-7) M) was reduced to a plateau level of about 30% of that in untreated cultures by 1 h of glucagon (2 X 10(-7) M) pretreatment, and induction by epinephrine (10(-5) M) pretreatment. The time courses of the stimulation of cAMP production by each hormone were similar in control and hormone-pretreated cells. There was no change in the concentration of hormone producing half-maximal stimulation of cAMP accumulation by epinephrine in desensitized cells and only a small increase in the concentration of glucagon producing half-maximal cAMP induction. Desensitization by glucagon was reversed to about 70% of control levels 1 h after placing treated cells in hormone-free medium, whereas desensitization by epinephrine was poorly reversible. Neither desensitization nor its reversal was affected by inhibition of protein or RNA synthesis. Cells pretreated with glucagon were desensitized equally toward glucagon and epinephrine, whereas epinephrine pretreatment caused, predominantly, desensitization toward epinephrine. Pretreatment of cultures with dibutyryl cAMP resulted in less inhibition of the stimulation of cAMP production by epinephrine than did pretreatment with the hormone itself. Depending on the cell preparation used, dibutyryl cAMP was either as effective or less effective than glucagon itself, but always caused some desensitization. The data are consistent with there being hormone-specific and nonspecific components involved in the overall process of desensitization toward glucagon and epinephrine, with a nonspecific component mediated by cAMP. PMID- 6253263 TI - Effects of sodium butyrate and 5-bromo-2'-deoxyuridine on the synthesis of human chorionic gonadotropin in human placental cells transformed by tsA mutants of simian virus 40. AB - The synthesis of hCG and its subunits was studied in simian virus 40 (SV40) tsA mutant-transformed human first trimester and term placental cells at 33 C (the temperature at which the cells have the transformed phenotype) and 40 C (the temperature at which the temperature-sensitive tsA transformants regain their nontransformed phenotype). In the presence of sodium butyrate at 33 C, synthesis of both hCG and hCG alpha was greatly induced in the tsA transformants. at 40 C, hCG synthesis was induced by sodium butyrate, although to a lesser extent than at 33 C. Yet, hCG alpha synthesis was inhibited by sodium butyrate at 40 C. In the presence of 5-bromo-2'-deoxyuridine (BrdUrd) at 33 C, hCG synthesis was not affected in the transformed first trimester placental cells and was induced in the transformed term placental cells. In the presence of BrdUrd at 40 C, hCG synthesis was induced in both forms of placental cells. The synthesis of the free hCG alpha-subunit appeared to be controlled differently. At 33 C, hCG alpha synthesis was also induced by BrdUrd. At 40 C, however, hCG alpha synthesis was inhibited by BrdUrd. hCG synthesis was induced and hCG alpha synthesis was inhibited by sodium butyrate and BrdUrd in the tsA-transformed placental cells grown at 40 C. Whereas the synthesis of both hCG and hCG alpha in choriocarcinoma cells has been reported to be inhibited by both sodium butyrate and BrdUrd. Our data indicate that the effects of sodium butyrate and BrdUrd on the production of hCG, but not hCG alpha, were different in the SV40 tsA-transformed placental cells and choriocarcinoma cells. PMID- 6253264 TI - Dependence of aldosterone stimulation in adrenal glomerulosa cells on calcium uptake: effects of lanthanum nd verapamil. AB - The calcium dependence of steroidogenic responses to angiotensin II, potassium, and ACTH was analyzed in isolated adrenal glomerulosa cells incubated with inhibitors of calcium uptake. Both lanthanum and verapamil reduced the stimulation of aldosterone production by each regulator in a dose-dependent manner, with only a moderate decrease in basal steroid production. The stimulation of aldosterone and cAMP production by ACTH was blocked by both antagonists, and the degree of inhibition was dependent on the concentration of ACTH employed. Increasing concentrations of verapamil caused an increase in th ACTH concentration required for half-maximal stimulation as well as a reduction in the maximum production of aldosterone. Aldosterone production by glomerulosa cells in response to angiotensin II or potassium was also decreased by lanthanum and verapamil, with no change in the concentration of angiotensin II required for half-maximal stimulation of steroidogenesis. Stimulation of pregnenolone synthesis by angiotensin II was also inhibited by verapamil, indicating that calcium is required for the action of angiotensin II at an early step in the steroidogenic pathway. The inhibitory action of verapamil upon angiotensin stimulated aldosterone production was overcome by increasing concentrations of calcium. Neither of the calcium antagonists affected the binding of angiotensin II to glomerulosa cells, placing the calcium requirement for the action of angiotensin II at a postreceptor locus. These results provide further evidence that angiotensin II and potassium increase aldosterone production in adrenal glomerulosa cells through a calcium-dependent mechanism, and indicate that calcium uptake is an essential requirement for the stimulation of aldosterone production by these two effectors. PMID- 6253265 TI - Effect of hypophysectomy and hormone replacement of hormone receptor levels and the growth of 7,12-dimethylbenz(a)anthracene-induced mammary tumors in the rat. PMID- 6253266 TI - Calcium-dependent actions of gonadotropin-releasing hormone on pituitary guanosine 3',5'-monophosphate production and gonadotropin release. AB - The effects of gonadotropin-releasing hormone (GnRH) on cGMP production and LH release in cultured rat pituitary cells are markedly dependent upon the extracellular calcium concentration. The absence of calcium from incubation media caused almost complete loss of the GnRH effects on cGMP production and LH release but did not change the stimulation of cAMP accumulation by GnRH in the pituitary of the adult male rat. In female rat pituitary cells, reduction of the extracellular calcium concentration increased the concentration of GnRH required to produce half-maximal LH release and decreased the maximal gonadotropin output but had no significant effect on basal LH release. The divalent cation ionophore A23187 stimulated LH release, and this action was dependent on extracellular calcium. Both GnRH and A23187 were found to have maximal effects when the calcium concentration was 0.6 mM, and their actions were not additive. The calcium antagonists, verapamil and lanthanum, caused concentration-dependent inhibition of the actions of GnRH, with half-maximal blockade values of 10(-5) and 3 X 10( 6) M, respectively, and had no effect on basal LH release. The binding of a radioiodinated GnRH analog, [D-Ser(t-Bu)6]des-Gly10-GnRH-N-ethylamide, to pituitary GnRH receptors was unchanged in the absence of extracellular calcium. These observations demonstrate that stimulation of pituitary cGMP production and LH release by GnRH is dependent on extracellular calcium. The site at which calcium is required during GnRH action is at a postreceptor locus before cGMP formation. PMID- 6253267 TI - Homologous and heterologous control of bone cell adenosine 3',5'-monophosphate response to hormones by parathoromone, prostaglandin E2, calcitonin, and 1,25 dihydroxycholecalciferol. AB - Desensitization of hormone-stimulated cAMP response to parathormone, prostaglandin E2, and calcitonin was characterized in isolated bone cells. Osteoclast- and osteoblast-like cells derived from mouse calvaria were incubated for up to 24 h with agents that cause bone resorption (parathormone, prostaglandin E2, or 1,25-dihydroxycholecalciferol) or with calcitonin, which inhibits bone resorption. The cells were then exposed to parathormone, prostaglandin E2, or calcitonin, and cAMP formation was quantified. Homologous desensitization (refractoriness to the second exposure to the same hormone) occurred for each hormone and was essentially complete after 30 min of preincubation. Heterologous desensitization to parathormone could be produced in both cell types by 1,25-dihydroxycholecalciferol and prostaglandin E2, but not by calcitonin. Heterologous desensitization was of lesser magnitude, requiring more than 8 h to reach significant proportions. In contrast, the cAMP response to calcitonin and prostaglandin E2 could not be altered by preincubation with any other hormone. Dibutyryl cAMP or 3-isobutyl-1-methylxanthine, which are bone resorptive agents, increased cellular cAMP and caused a slowly developing refractoriness to parathormone, prostaglandin E2, and calcitonin. Calcium (5 mM), an agent which mimics the biochemical action of parathormone in the bone cells but does not affect cAMP similarly desensitized the cells to parathormone, but not to calcitonin and only slightly to prostaglandin E2. These data suggest that heterologous desensitization of bone cells to parathormone results from the initiation of resorption by any agent regardless of whether cAMP is formed during activation of the cells. According to this concept, homologous desensitization to parathormone could involve two components: a rapid phase (< 30 min) and a long term phase, possibly stemming from initiation of resorption. PMID- 6253268 TI - Responsiveness and maximum secretory capacity of isolated fetal lamb adrenocortical cells throughout the last third of gestation. AB - Although considerable evidence implicates increased fetal adrenal function as a major factor in the initiation of parturition in the sheep, the mechanism responsible for this increased activity has not yet been determined. We have investigated the development of the function of fetal lamb adrenal cortical cells dispersed in vitro. There was no change in the sensitivity of the cells to synthetic ACTH (ACTH1-24), as demonstrated by the concentraton of ACTH1-24 producing a 50% maximum response in corticoid secretion. This finding does not support the suggestion that there is a qualitative change in fetal adrenal receptor function as term approaches. No stimulation of corticoid was observed after the administration of alpha MSH or PRL in vitro at any gestational age or of alpha MSH in vivo in four fetuses at 125--130 days gestation. Both the maximum output and the 50% maximum response in corticoid secretion of adrenal cells from term fetuses were similar to those of adrenal cells from adult ewes. A significant increase in the maximum output of corticoids per cell in response to ACTH1-24 occurs as early as 107 days gestation and continues steadily to term. PMID- 6253269 TI - Effects in vivo of vitamin D metabolites and 17 beta-estradiol on parathyroid hormone-dependent formation of adenosine 3',5'-monophosphate in rat bone. AB - We used an in vivo infusion technique to assess the hypothesis that vitamin D metabolites and estrogens modulate tissue responsiveness to parathyroid hormone via effects on the adenylate cyclase-cAMP system. After treatment with these agents for 3-4 days, rats were thyroparathyroidectomized. Twenty-four hours later, parathyroid extract (PTE) was infused, and cAMP in calvaria was measured. The response to PTE was achieved by 2 min and represented a 4-fold increase in the tissue concentration of cAMP at the highest dose of hormone tested. Treatment with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], did not affect cAMP levels in bone. However, 24,25-dihydroxyvitamin D3 [24,25-(OH)2D3], either 0.25 or 1.25 micrograms daily, led to a major increase in PTE-stimulated cAMP formation, a result which persisted when carried out in chronically thyroparathyroidectomized animals. This effect did not reflect direct stimulation of adenylate cyclase or inhibition of cyclic nucleotide phosphodiesterase from bone by the vitamin metabolite, nor did it operate via the 1,25-(OH)2D3 receptor. 24,25-(OH)2D3 treatment also increased cAMP concentrations in renal cortical slices, but not in liver. Adenylate cyclase activity in kidneys from 24,25-(OH)2D3-treated rats was not different from that found in control tissue, but total cytosol phosphodiesterase activity was diminished. 17 beta-Estradiol, over a daily dose range of 2.5 micrograms to 5.0 mg, lowered basal cAMP levels but did not alter PTE-stimulated cAMP production. We conclude that modulation of PTH action in bone by estrogen does not involve modification of the acute cAMP response to PTH. Further, the results support the concept that there are unique actions of 24,25 (OH)2D3 on bone and kidney which are not duplicated by 1,25(OH)2D3. PMID- 6253270 TI - Gonadotropin release and cyclic nucleotides: evidence for luteinizing hormone releasing hormone-induced elevation of guanosine 3',5'-monophosphate levels in gonadotrophs. AB - To investigate the participation of cyclic nucleotides in LHRH-mediated gonadotropin release, cells from the anterior pituitaries of 15-day-old female rats were fractionated on an albumin gradient by sedimentation at unit gravity. gonadotrophs and somatotrophs were detected in the fractions by histology and RIA of hormone content, then the cells were pooled into three subpopulations and cultured overnight. The effect of LHRH on hormone release and cyclic nucleotide content was examined by incubation in the presence or absence of the releasing hormone. After 60 min, LHRH (5 nM) had induced a 5- to 6-fold increase in LH release only from the cells in the subpopulation which was enriched in gonadotrophs. At no time did LHRH influence cAMP levels in any of the cells; however, the cGMP content of the cells in the gonadotroph-containing pool rose to twice that in the controls after only 15 min in the presence of LHRH. The increase in cGMP concentration in the cells was at or near maximum by the time of the initial sampling; however, LH continued to accumulate in the medium over the entire test period. These observations support the view that cGMP is involved in the action of LHRH. PMID- 6253271 TI - Dose- and age-dependent effects of prolactin (PRL) on luteinizing hormone- and PRL-binding sites in rat leydig cell homogenates. PMID- 6253272 TI - Glucocorticoids increase pulmonary beta-adrenergic receptors in fetal rabbit. AB - beta-Adrenergic agonists stimulate surfactant release and decrease fluid in lung alveoli of fetuses. Both effects are most evident toward the end of gestation. We used [3H] dihydroalprenolol (DHA) to investigate the development of pulmonary beta-adrenergic receptors in rabbit fetuses and to study the effect of glucocorticoid treatment on the beta-receptor number. In the lung particulate preparation, DHA binding was rapid, reversible, stereoselective, and of high affinity. The order of potency for adrenergic agonists in competing for DHA binding was isoproterenol > epinephrine = norepinephrine, which is typical of interactions at a beta 1-adrenergic receptor. Using DHA, we demonstrated that the concentration of pulmonary beta-receptors increased significantly between 28 and 31 days of gestation; however, there was no change in the dissociation constant during gestation. After injecting betamethasone (0.17 mg/kg, 24 hours) into rabbits at 25 days of pregnancy, we found that the concentration of pulmonary beta-receptors increased from 44.2 +/- 6.6 fmol/mg protein in untreated fetuses to 77.9 +/- 5.6 fmol/mg protein in treated fetuses. However, this treatment did not affect the DHA binding sites in the fetal rabbit heart. Maternal treatment with the T3 analogue 3,5-dimethyl-3'-isopropyl-L-thyronine (0.5-1 mg/kg) at a dosage which increased both surfactant synthesis and release did not alter pulmonary receptor concentration. Our results indicate that the concentration of pulmonary beta-adrenergic receptors increases in the fetus at term and suggest that this increase is stimulated by endogenous glucocorticoid in fetal circulation. PMID- 6253273 TI - Interaction of glucagon and epinephrine in the regulation of adenosine 3',5' monophosphate-dependent glycogenolysis in the cultured fetal hepatocyte. AB - The hormonal control of glycogenolysis has been studied in 3-day-cultured fetal rat hepatocytes which contained stored glycogen. A single addition of 10 nM glucagon or 10 nM epinephrine produced an identical maximal glycogenolytic response, which developed within 4 h and ceased thereafter. The amount of glycogen degraded represented 60% of the stored glycogen or 95% of the newly synthesized glycogen after a 4-h preincubation period in the presence of [14C]glucose. The latter result demonstrates that both hormones interact on the same hepatocytes. Stimulation of glycogenolysis by glucagon or or epinephrine was preceded by an accumulation of intracellular cAMP. From the decreasing order of potency of isoproterenol, epinephrine, norepinephrine, and phenylephrine to activate glycogenolysis, it can be concluded that the epinephrine effect is mainly mediated by beta-adrenergic receptors. When glucagon and epinephrine were added simultaneously at maximal concentrations, the glycogenolytic effects were not additive. Moreover, when epinephrine was added 4 h after glucagon, it elicited a second glycogenolytic response, so that the amount of glycogen degraded represented 80% of the stored glycogen. At this stage, a second addition of glucagon was ineffective, and the extent of the glucagon-induced loss of response depended on the size of the first dose of hormone. Cell densensitizatin to glucagon for glycogenolysis was closely related to the associated response in cAMP production. This desensitization was found to be highly specific for glucagon and was accompanied by a defect in specific glucagon binding. The occurrence of a specific negative regulation of the response to glucagon explained how epinephrine was able to mobilize glycogen accumulated in the continued presence of glucagon during hepatocyte development in culture. PMID- 6253274 TI - Lithium-induced polyuria: effect of lithium on adenylate cyclase and adenosine 3',5'-monophosphate phosphodiesterase in medullary ascending limb of Henle's loop and in medullary collecting tubules. AB - We investigated the effects of hyperosmolality, chronic treatment with lithium chloride (LiCl), and the addition of LiCl in vitro on vasopressin-sensitive (VP) adenylate cyclase (AdC) and cAMP phosphodiesterase (cAMP-PDIE) activities in the medullary thick ascending limb of Henle's loop (MAL) and medullary collecting tubule (MCT) microdissected from the outer medulla of the rat kidney. A hyperosmolar medium (800 mosmol) markedly enhanced AdC activity stimulated by 10( 6) M VP specifically in MCT, while having little effect or slightly decreasing VP stimulated AdC in MAL, compared to activities under standard isotonic conditions. Hyperosmolality decreased cAMP-PDIE activity to about the same degree in MAL and MCT. Inclusion of LiCl in the incubation medium (15-20 mM) caused a significant dose-dependent inhibition of VP-stimulated AdC activity in both MAL and MCT, but had no effect on CAMP-PDIE in either segment. AdC and cAMP-PDIE activities in MAL and MCT from chronic LiCl-treated polyuric rats did not differ from controls when assayed under standard isotonic conditions. However, when assayed in a hyperosmolar (800 mosmol) medium, VP-sensitive AdC activity was significantly lower (P < 0.01) in MCT from LiCl-treated rats compared to control levels, while VP-sensitive AdC in MAL did not differ in LiCl-treated and control rats. The present results suggest that lowered VP-sensitive AdC activity in MCT of LiCl treated polyuric rats may contribute to the observed lower concentrating ability and collecting tubule resistance to VP. Inhibition of VP-sensitive AdC in MAL as well as MCT by the acute addition of LiCl in vitro may explain the decreased urinary diluting ability observed with acute infusions of Li salts in vivo in the rat. PMID- 6253275 TI - Characterization and regulation of receptors for epidermal growth factor in mouse calvaria. AB - Epidermal growth factor (EGF) has been shown to stimulate bone resorption in mouse calvaria in organ culture by a prostaglandin-mediated mechanism. In this report we demonstrate and characterize specific receptors for EGF in mouse bone. Binding of tracer quantities of [125I]iodo-EGF reached a maximum after 2 h of incubation at 37 C and began to decrease only after 8 h of continuous exposure to EGF. Scatchard analysis of equilibrium binding data showed a single class of binding sites with a Kd = 2 X 10(-9) M present at a concentration of 3.8 X 10(10) sites/calvarium. The association (ki = 4.4 X 10(6) M-1 min-1) and dissociation (k2 = 0.015 min-1) rate constants for the approach to equilibrium were calculated, and there was no evidence of cooperativity between binding sites. Pretreatment of bones with EGF for 12 h produced a decrease in EGF binding of about 20%, and a maximum decrease to 50-60% of control binding after 48 h of treatment. Decreased binding was due solely to a decrease in the number of receptors rather than to a change in receptor affinity. This down-modulation of receptors occurred even when the bone resorption-stimulating action of EGF was blocked completely by indomethacin, and thus seemed to be triggered only by occupancy of receptors by EGF. Treatment of calvaria with parathyroid hormone, 1,25-dihydroxyvitamin D3, calcitonin, and prostaglandin E2 produced no net change in the number or affinity of EGF receptors in bone. EGF also produced no change in the total DNA content of mouse calvaria. We conclude that mouse bone contains specific high affinity receptors for EGF, and that this experimental system is useful for investigations on EGF receptor modulation and the biological actions of EGF on bone. PMID- 6253276 TI - Effects of immunoglobulins upon the interaction of thyrotropin with receptor in human fat tissue. AB - TSH bound to human fat membranes is shown to be unusually sensitive to the addition of immunoglobulin G (IgG). Significant displacement was observed with 10 microgram/ml, and 50% displacement was obtained with 50-100 microgram/ml IgG prepared from control sera pooled from euthyroid subjects. It was not possible to demonstrate increased TSH displacement by IgG preparations from sera of thyrotoxic compared to that of euthyroid subjects using human fat membranes, as was demonstrable with human thyroid membranes. The increased sensitivity of fat membranes to IgG was not due to nonspecific protein interactions and is suggested to derive from interactions with Fc receptors associated with fat membranes. PMID- 6253277 TI - Characterization of a specific receptor for somatomedin C (SM-C) on cultured human lymphocytes: evidence that SM-C modulates homologous receptor concentration. AB - A membrane receptor for somatomedin C (SM-C) on cultured IM-9 cells has recently been reported. The current studies were undertaken to further characterize this intact cellular receptor in terms of both kinetics and specificity and to investigate the ability of SM-C to induce homologous receptor loss. The binding of [125I]iodo-SM-C was rapid, achieving a steady state within 90 min and was greater than 95% reversible. Specific binding at 15C averaged 25-30% for 20 X 10(6) cells/ml. Competition for binding was observed at SM concentrations as low as 2 mU/ml, with half-maximal displacement of [125I]iodo-SM-C at SM concentrations of 33 mU/ml (3.33 X 10(-9) M). Insulin-like growth factor I (IGF I) and a purified SM-C preparation were approximately equipotent in their ability to displace [125I]iodo-SM-C from the IM-9 receptor. The relative potencies of other growth-related peptides, in comparison with SM-C/IGF-I, were IGF-II (1:10), multiplication stimulating activity (1:10), insulin (1:100), and hGH (nonreactive). Preexposure of IM-9 cells to SM-C at 37 C resulted in a time- and concentration-dependent reduction in [125I]iodo-SM-C. A 10-15% decrease in binding was observed after preincubation with SM in concentrations of 7 mU/ml. Preincubation with 100 mU/ml SM resulted in 50% reduction in binding, but no further decreases were observed after preincubation with higher concentrations of SM (up to 1 U/ml). Scatchard analysis indicated that the reduction in binding was due to a loss of available specific receptors on the cell membrane. These data indicate that the IM-9 cell possesses a specific SM receptor and that SM-C and IGF-I compete equally for occupancy. Furthermore, the data provide a direct demonstration in cell culture that SM-C, like insulin and growth hormone, can modulate homologous receptor concentrations and potentially alter target-cell sensitivity. PMID- 6253278 TI - Metabolism of high density lipoprotein by human fetal adrenal tissue. AB - The role of lipoproteins as a source of the cholesterol utilized for steroidogenesis by human fetal adrenal (HFA) tissue was investigated previously. It was found that low density lipoprotein (LDL) was the lipoprotein preferred as a source of cholesterol for steroidogenesis by the HFA. [125I]Iodo-LDL was taken up and degraded by HFA tissue in organ culture, and the degradation of [125I]iodo LDL was stimulated when ACTH (1 microgram X ml-1) was present in the culture medium. Others have shown that high density lipoprotein (HDL) is utilized as a source of cholesterol for steroidogenesis by rat adrenocortical cells in vitro and by the adrenals of the adult rat in vivo. In the present investigation we evaluated the metabolism of [125I]iodo-HDL by HFA tissue. [125I]iodo-HDL uptake by the HFA tissue increased in a linear manner with time and as the concentration of [125I]iodo-HDL in the culture medium was increased. However, there was little degradation of [125I]iodo-HDL by HFA. Moreover, preincubation of HFA tissue in medium containing ACTH (1 microgram X ml-1) or HDL, in various concentrations, did not affect the rate of uptake and degradation of [125I]iodo-HDL. The rate of degradation of [125I]iodo-LDL was found to decrease to low levels as the concentration of nonradiolabeled LDL in the culture medium was increased, whereas nonradiolabeled HDL had little effect on the degradation of [125I]iodo-LDL. HFA tissue fragments were incubated in medium containing ACTH plus lipoprotein-poor serum (LPPS) alone or LPPS plus HDL in various concentrations (50-1000 microgram X ml-1). The medium was changed daily and assayed for dehydroisoandrosterone sulfate and cortisol. In the presence of HDL, steroid secretion rates were no greater than those attained by HFA maintained in medium containing LPPS. It is concluded that the HFA utilizes cholesterol derived from LDL for steroidogenesis and that HDL is not metabolized efficiently by the human fetal adrenal. PMID- 6253279 TI - Glucose dependence of thyrotropin-stimulated thyroid hormone formation. AB - TSH (100 mU/ml) stimulation of organic binding of iodide, including formation of T4, in bovine thyroid slices was 3-fold greater when the incubation medium contained glucose; this effect of glucose was apparent at 0.1 mM and was maximal at 1 mM. TSH at 5 mU/ml enhanced organification of iodide in calf thyroid slices only with the presence of glucose in the medium. These effects of glucose are not mediated by mechanisms involving iodide transport. TSH stimulation of O2 consumption of slices was also significantly greater in glucose-enriched medium. Glucose was also required for maximal increase of iodide organification in response to dibutyryl cAMP and prostaglandin E1 in canine thyroid slices. Glucose did not affect the TSH-stimulated increase in the cAMP content of calf thyroid slices. Galactose, fructose, or pyruvate could replace glucose in supporting TSH stimulation of organic binding; TSH increased oxidation of [1-14C]galactose, [U 14C]fructose, or [3-14C]pyruvate, as well as that of [1-14C]glucose. In thyroid slices, TSH enhanced the oxidation of formate, a process believed to be mediated by endogenous H2O2, only in glucose-supplemented medium. The addition of of H2O2 or a H2O2-generating system (tyramine) to the medium greatly increased the organic binding of iodide in thyroid slices; this stimulation, however, did not require glucose. Since both TSH- and cAMP-dependent thyroid hormone formation and H2O2 production were augmented by glucose, while glucose supplements had no effect on hormone formation in the presence of exogenous H2O2, it is concluded that the mechanism whereby glucose potentiates the observed responses to TSH involves enhanced intrathyroidal generation of H2O2. PMID- 6253280 TI - Binding of thyroid hormones in vivo by hepatic nuclei of Rana catesbeiana tadpoles at different stages of metamorphosis. PMID- 6253281 TI - Organ distribution of the cytoplasmic 1,25-dihydroxycholecalciferol receptor in various mouse tissues. PMID- 6253282 TI - Direct inhibitory effect of gonadotropin-releasing hormone upon luteal luteinizing hormone receptor and steroidogenesis in hypophysectomized rats. AB - The effects of gonadotropin-releasing hormone (GnRH) and its potent agonist [des Gly10, D-Leu6-N alpha Me) Leu7, Pro9,NHEt-GnRH (GnRH-A)] on ovarian luteal functions maintained by PRL were studied in vivo and in vitro. Hypophysectomized, diethylstilbestrol-treated female rats were primed with FSH for 2 days, followed by an ovulating dose of LH or hCG. Two days later, ovarian luteal functions were maintained by daily injections of 250 microgram PRL for 3 days. PRL treatment increased the serum progesterone level from 13.0 +/- 0.5 to 298 +/- 24 ng/ml and increased the ovarian hCG-binding capacity from 5.8 +/- 1.3 to 584 +/- 86 ng bound hCG/ovary. In contrast, concomitant treatment with GnRH or GnRH-A resulted in dose-dependent decreases in the PRL-induced increase of serum progesterone and ovarian LH/hCG receptor content. GnRH at 100 microgram/day caused a 60% decrease in serum progesterone and an 80% decrease in ovarian LH receptor content, whereas GnRH-A was effective at a 1-microgram dose level. Neither GnRH nor GnRH-A affected the binding affinity (Kd) of ovarian LH receptor. The direct inhibitory effects of GnRH and GnRH-A upon granulosa-luteal cell function were also tested in vitro. FSH treatment for 2 days induced functional LH and PRL receptors in cultured PRL, increased (by approximately 3-fold) progesterone production by these granulosa-luteal cells, whereas concomitant treatment with GnRH-A inhibited progesterone production in a dose-dependent manner. Thus, these studes demonstrated that GnRH and GnRH-A exert direct inhibition on ovarian luteal functions by decreasing LH receptor and progesterone production in vivo as well as inhibiting progesterone production by cultured granulosa-luteal cells in vitro. PMID- 6253283 TI - Pituitary-dependent growth hormone receptors in rabbit and sheep liver. PMID- 6253284 TI - Luteinizing hormone-receptor interaction in the testis: progressive decrease in reversibility of the hormone-receptor complex. PMID- 6253285 TI - Calcium-regulated phosphodiesterase in bovine parathyroid cells. AB - The potential role of calmodulin-activated phosphodiesterase in regulating parathyroid function was assessed in dispersed bovine parathyroid cells. Boiled parathyroid cell sonicates contained 40-50 ng/10(6) cells of calmodulin, as determined by the activation of calmodulin-deficient phosphodiesterase. Bovine parathyroid calmodulin appeared to be similar to, if not identical with, pure porcine brain calmodulin by a number of criteria. 1) Both eluted as single peaks at similar ionic strengths on DEAE-cellulose ion exchange chromatography. 2) Both activated calmodulin-deficient phosphodiesterase over a similar range of calcium concentrations. 3) In both cases, calmodulin-activated phosphodiesterase activity was specifically inhibited by similar concentrations of the phenothiazine trifluoperazine. In sonicates of bovine parathyroid cells, both cAMP and cGMP phosphodiesterase activities were inhibited by EGTA and restored by the addition of excess calcium. Moreover, calmodulin-activated phosphodiesterase could be directly demonstrated in cell sonicates subjected to DEAE-cellulose chromatography. When chromatography was carried out in the absence of EGTA, calmodulin and calcium-activated phosphodiesterase comigrated at 0.22 M NaCl. In the presence of EGTA, calmodulin-activated phosphodiesterase eluted at 0.13 M NaCl, while calmodulin eluted between 0.25-0.4 M NaCl. These results directly demonstrate the presence of calmodulin and calmodulin-activated phosphodiesterase in bovine parathyroid cells and suggest that this enzyme complex may contribute to the calcium-induced reduction of intracellular cAMP content as well as parathyroid hormone release in this cell type. PMID- 6253286 TI - Chronic regulation of rat thyroid prostaglandin synthetase activity by endogenous thyrotropin. AB - Prostaglandin (PG) synthetase activity was measured in the rat thyroid after hypophysectomy, T4, and methylthiouracil treatment in order to explore the possibility that PG synthetase is subject to chronic control by endogenous TSH. T4 treatment (5 mg/liter drinking water) lowered PG synthetase activity, as measured in whole homogenates, by 22% and 31% after 2 and 4 days, respectively. Similarly, PG synthetase activity was reduced by 16% and 42% 2 and 4 days after hypophysectomy. Methylthiouracil treatment (100 mg/liter drinking water) effected 51% and 78% increases in synthetase activity by days 2 and 4, respectively. Additionally, differential effects with regards to PGE2 to PGF 2 alpha ratios were observed. The limited prostaglandin-catabolizing capacity of the rat thyroid warrants the conclusion that the observed TSH effects are expressed at the level of the PG synthetase complex. PMID- 6253287 TI - Influence of cholera toxin on in vitro refractoriness to thyrotropin of thyroids from rats fed propylthiouracil. AB - Using an increase in the concentration of cAMP as an index of stimulation, we previously reported that in vitro thyroid tissue of rats fed a goitrogenic diet (0.1% propylthiouracil in Purina) were unresponsive to TSH. We now show that the addition of cholera toxin (0.1-1.0 microM) to fragments of normal thyroid enhanced the concentration of cAMP. Subsequent exposure of the tissue to TSH resulted in a further increase in the concentration of cAMP, and there was statistical evidence of interaction or potentiation between the effects of TSH (20 mU/ml) and cholera toxin (1.0 microM). With fragments of thyroid from animals fed propylthiouracil (i.e. unresponsive in vitro to TSH), an increase in the concentration of cAMP was effected by 1 or 9 microM cholera toxin, and prior exposure to 9 microM toxin caused the tissue to be responsive to TSH. Unresponsiveness of the goitrous tissue was associated with a reduced capacity of the membrane to bind [125I]iodo-TSH although the affinity of the binding sites was unaffected. Cholera toxin at 0.1 microM enhanced and at 1 microM diminished the binding of [125I]iodo-TSH to membranes from either normal or goitrous glands, and these effects also reflected influences on the capacity rather than on the affinity of the binding sites. It is postulated that the unresponsiveness to TSH of thyroid tissue from rats fed propylthiouracil represents a down-regulation of receptor capacity, and this is effected by the binding sites becoming relatively inaccessible, rather than nonexistent. PMID- 6253288 TI - Adrenocorticotropin analogs and glucocorticoids in the hypophysectomized rat. I. Effects on liver polyribosomes and rough endoplasmic reticulum. AB - Hypophysectomy decreased polyribosome aggregation and activity in rat liver. Polyribosome aggregation was measured by sucrose density gradient analysis and polyribosome activity was determined by the incorporation of labeled amino acids into protein in a cell-free system using pH 5 enzymes from sham-operated rats. Hypophysectomy also totally disorganized the rough endoplasmic reticulum of hepatocytes, as shown by electron micrographs. The sc administration of the ACTH fragments, Hoe 433 (corticotropic) and Org 2766 (noncorticotropic), and of glucocorticoids (dexamethasone or corticosterone) to hypophysectomized rats restored these parameters to the levels recorded in sham-operated rats in a dose dependent fashion 5 h after injection; the effects were maintained until at least 24 h. The sc administration of the noncorticotropic but metabolically less stable fragment, ACTH-(1-10), had only a partial effect. The potency of a noncorticotropic ACTH fragment (Org 2766) in hypophysectomized rats suggests that ACTH may act on liver protein synthesis without the intervention of glucocorticoids or pituitary hormones. PMID- 6253290 TI - Effects of thyrotropin and cholera toxin on the thyroidal adenylate cyclase adenosine 3',5'-monophosphate system. AB - The present experiments examined the relationship between cholera toxin and TSH stimulation of the adenylate cyclase system in bovine thyroid tissue. Preincubation of thyroid slices for 20 min at 4 C with a maximal concentration of cholera toxin (100 microgram/ml) did not impair the subsequent stimulation of cAMP by submaximal amounts of TSH (1 mU/ml) during a 5-min incubation at 37 C. Incubation of cholera toxin or TSH with mixed gangliosides, followed by the addition of thyroid slices resulted in inhibition of the cholera toxin but not the TSH stimulation of cAMP formation. Previous exposure of thyroid slices to TSH induced refractoriness to subsequent stimulation of cAMP formation by TSH, but the response to cholera toxin was unchanged. NAD is necessary for cholera toxin, but not TSH, stimulation of adenylate cyclase. In the absence of NAD, cholera toxin inhibited the effect of maximal concentrations of TSH and prostaglandin E1 on adenylate cyclase activity but had no effect on NaF stimulation. In the presence of NAD, the stimulation of adenylate cyclase activity of bovine thyroid plasma membranes by a maximal amount of TSH was not influeced by maximal amounts of cholera toxin. Cholera toxin had a biphasic action on the binding of [125I]iodo-TSH, with low concentrations enhancing and high concentrations inhibiting binding. TSH augmented the binding of [125I]iodo-cholera toxin over the range of 1-100 mU/tube. Cholera toxin at 10 microgram/ml maximally inhibited binding. In addition to the requirement for ribosylation of adenylate cyclase, the present results indicate that the mechanisms of action of TSH and cholera toxin on cAMP formation are different. PMID- 6253289 TI - Adrenocorticotropin analogs and glucocorticoids in the hypophysectomized rat. II. Effects on cerebral cortex polyribosomes. AB - The capacity of free polyribosomes from rat cerebral cortex to incorporate labeled amino acids into protein (polyribosome activity) was compared in normal, hypophysectomized, and treated hypophysectomized rats. Polyribosome activity was measured in a cell-free system using a pH 5 supernatant from sham-operated rats. The polyribosome activity of hypophysectomized rats was 10-20% less than that of sham-operated rats. Subcutaneous treatment of hypophysectomized rats daily for 10 days with ACTH, corticotropic ACTH fragments [10-2- microgram of ACTH-(1-24), ACTH-(1-23), or Hoe 433 (ACTH-(1-17))], or glucocorticoids (1 mg corticosterone or 10 microgram dexamethasone) stimulated activity to a level 25-50% higher than that in sham-operated rats. Polyribosome aggregation, as measured by sucrose density gradient analysis, was also greater in treated hypophysectomized rats than in sham-operated rats. On the other hand, a daily sc dose of 100 microgram of the noncorticotropic fragment, ACTH-(1-10), did not stimulate brain polyribosome activity in hypophysectomized rats but merely restored it to the level observed in sham-operated rats. The present study suggests that stimulation of cerebral protein synthesis by ACTH and corticotropic ACTH analogs may be partly due to their ability to promote adrenal steroid secretion. Their stimulatory effect and that of glucocorticoids might explain their physiological roles during stress and learning. PMID- 6253291 TI - Parathyroid hormone does not increase nephrogenous cyclic AMP excretion by the dog. AB - The renal excretion of nephrogenous cyclic AMP (NcAMP) increases in response to parathyroid hormone (PTH) in man, and thereby serves as a test of parathyroid function. However, during studies of calcium-PTH (PTH) in man, and thereby serves as a test of parathyroid function. However, during studies of calcium-PTH interrelationships in dogs we observed no change in total urinary cAMP (UcAMP) excretion when endogenous plasma PTH levels were increased up to 10-fold. This study was designed to investigate the effects of physiologic and pharmacologic levels of PTH on NcAMP and UcAMP excretion in the dog. Maintaining plasma Ca 2 mg/dl below normal for 40 minutes caused an 8-fold increase in plasma PTH concentration, a 50% increase in the urinary fractional excretion of phosphate (FEP) but no changes in plasma cAMP levels or in UcAMP or NcAMP excretion. Infusion of a pharmacologic amount of parathyroid extract (15 U/min for 20 min) increased plasma cAMP 5-fold, UcAMP excretion 3-fold and FEP by 50% but was without effect on NcAMP excretion. We conclude that NcAMP excretion is not stimulated by PTH in the dog and thus cannot be used as an index of PTH action in vivo. The increase in UcAMP excretion by pharmacologic amounts of PTH results from glomerular filtration of increased plasma cAMP, which may be generated in bone. PMID- 6253292 TI - Gonadotropin release from pituitary cultures following activation of endogenous ion channels. AB - In primary rat pituitary cell cultures, activation of Na+ channels resulted in Na+ and Ca2+ dependent gonadotropin release. This occurred with the same efficacy and over the same time course as that stimulated by gonadotropin releasing hormone (GnRH). In contrast, GnRH required extracellular Ca2+, but not Na+ for its action. These results indicate that the gonadotrope has ion channels which resemble those found in neural tissues. PMID- 6253293 TI - Binding sites for gonadotropins in the ovary of immature and adult mice. AB - Binding sites for gonadotropins in the mouse ovary were studied using the immunohistochemical technique. Binding sites for LH were localized in the interstitial cells and theca as well as granulosa cells of large follicles. Binding sites for FSH were demonstrated in the interstitial cells and granulosa cells of small follicles. In immature mice very few binding sites for both the gonadotropins were observed until day 21 of age. An intense staining reaction for peroxidase was observed in the ovary of 24-day old mouse. In adult mice, maximum number of binding sites for FSH were demonstrated in the ovary in estrus and metestrus stage of the cycle, respectively. A good correlation between the circulating levels of gonadotropins and binding sites for them in the ovary could be noted in the cycling but not in the prepubertal mice. PMID- 6253294 TI - Basal plasma aldosterone levels and tetracosactid-induced increase of aldosterone secretion in conscious male rabbits: lack of correlation with glucocorticosteroid levels. AB - The adrenocortical secretory activity under basal conditions and after treatment with tetracosactid (1-24ACTH) has been investigated in chronically cannulated male rabbits. Basal plasma concentrations of glucocorticosteroids (0.74 micrograms/100 ml) and aldosterone (78 pg/ml) have been determined in a greater number of animals. No significant positive correlation between basal glucocorticosteroid and aldosterone plasma levels could be found. After intravenous injection of 2.5, 5.0, 10.0 and 20.0 micrograms/kg body weight tetracosactid glucocorticosteroid concentrations were significantly elevated between 40--100 min after administration; aldosterone release, on the other hand, was significantly increased only after injection of 10.0 or 20.0 micrograms/kg body weight tetracosactid between 20--60 min after injection. After administration of high tetracosactid doses glucocorticosteroid and aldosterone plasma concentrations were significantly correlated (10.0 micrograms/kg: r = 0.62; 20.0 micrograms/kg: r = 0.26). Because of the relative insensitivity of the zona glomerulosa cells to tetracosactid administered intravenously, it is concluded that ACTH is only of minor importance in the regulation of aldosterone secretion in the rabbit. PMID- 6253296 TI - [Nuclear and cytosol thyroxine and triiodothyronine receptors in the rat pituitary gland]. PMID- 6253295 TI - [Role of cytosol receptor in the regulation of deiodination of thyroxine to triiodothyronine in the microsomal fraction of rat liver]. PMID- 6253297 TI - [Detection of specific prolactin binding sites in cell membranes of the rat liver]. PMID- 6253298 TI - A rare tumor of the esophagus: the granular cell myoblastoma. Report of a case and review of the literature. AB - In 1931, Abrikossoff described a tumor, usually benign, which only rarely appears in the esophagus. In a 30-year-old man, we found an 8 mm tumor in the distal esophagus; it was removed surgically. We discovered 30 similar cases in the literature. Characteristics and treatment are discussed. PMID- 6253299 TI - Pulmonary function of control and industrially exposed Nigerians in asbestos, textile, and toluene diisocyanate-foam factories. PMID- 6253300 TI - Cyclic AMP in pancreatic and biliary secretion of children with chronic intrahepatic cholestasis and cystic fibrosis. PMID- 6253301 TI - Non-thymic malignant lymphomas induced in C57BL/6 mice by cloned dualtropic viruses isolated from hematopoietic stromal cell lines. PMID- 6253302 TI - Continuing studies of feline sarcoma virus induced tumors in newborn lambs and in kittens: a model to study comparative neoplasia. PMID- 6253303 TI - Prevention of early postmenopausal bone loss: controlled 2-year study in 315 normal females. AB - With the aim of preventing postmenopausal bone loss, a placebo-controlled double blind trial of 2 years duration was performed. We randomized 315 healthy volunteers in their early natural menopause to seven treatment and three placebo groups: 17 beta-oestradiol, oestriol and sequential norethisteron (hormones); bendroflumethiazide 5 mg/day (thiazide); hormones and thiazide; sodium fluoride 20 mg/day; vitamin D3 2000 IU/day (D3); fluoride and D3; and 1 alpha (OH) vitamin D3 0.25 microgram/day (1 alpha D3). All participants were given daily calcium supplement of 500 mg. Every 3 months we measured the bone mineral content (BMC) of both forearms by photon absorptiometry and chemical quantities in blood and 48 h urinary collections. The study was completed by 264 (84%). The combined placebo groups showed a linear fall in BMC reaching 3.3% after 2 years (P < 0.001). Hormones and hormones and thiazide led to a 2.5% gain in BMC (P < 0.01). Thiazide alone postponed the BMC fall for 6 months. After 2 years the thiazide group showed a BMC fall of 1.5% (P < 0.05), less than that of the placebo group (P < 0.05). BMC declined by 3.6%, 4.5%, 3.7% and 3.7% during the respective use of fluoride, D3, fluoride and D3 and 1 alpha D3. Nevertheless, the urinary calcium excretion during 1 alpha D3 and D3 treatment was 1--1.5 mmol/day higher than in the placebo groups. Apparently, there is no real alternative to oestrogen/gestagen in the prevention of postmenopausal osteoporosis. PMID- 6253304 TI - Linkage relationship between TK and SV40 T-antigen genes in the SV40-transformed WI98VaD human cell line. PMID- 6253305 TI - Studies of microbial toxins in Xenopus laevis oocytes. PMID- 6253307 TI - Changes in cAMP and fibronectin concentrations in adherent and suspension forms of a hybrid cell line. PMID- 6253306 TI - Redistribution of myosin during morphological reversion of Chinese hamster ovary cells induced by db-cAMP. PMID- 6253308 TI - Calcitonin-responsive adenylate cyclase in cultured F9 embryonal carcinoma cells. PMID- 6253309 TI - Localization of frog retinal pigment epithelium Na+-K+ ATPase. PMID- 6253310 TI - Chemiluminescent measurement of free radicals and antioxidant molecular protection inside living rat-mitochondria. PMID- 6253311 TI - Aging of collagen: comparative rates in four mammalian species. PMID- 6253312 TI - Diurnal changes in cyclic nucleotide levels in the hypothalamus of the rat. AB - The concentrations of cAMP and cGMP in the rat hypothalamus varied considerably over a 24-h period. The cAMP levels were found to be relatively higher in the morning and lower during the afternoon and night. Cyclic GMP levels reached highest values during the period of darkness and were lowest during the day. Deprivation of food did not have any appreciable effect on the pattern of these changes. PMID- 6253313 TI - Cyclic nucleotide metabolism in mouse brain during seizures induced by bicuculline or dibutyryl cyclic guanosine monophosphate. PMID- 6253314 TI - Entamoeba histolytica: cytopathogenicity, including serum effects on contact dependent and toxin-induced lysis of hamster kidney cell monolayers. PMID- 6253315 TI - Solution spatial structure of apamin as derived from NMR study. PMID- 6253316 TI - Animal rhodopsin as a photogenerator of an electric potential that increases photoreceptor membrane permeability. PMID- 6253317 TI - Heparin facilitates the induction of LH receptors by FSH in granulosa cells cultured in serum-enriched medium. PMID- 6253318 TI - Classification of an eIF-2phosphatase as a type-2 protein phosphatase. PMID- 6253320 TI - Functional activation by glucagon of glucose 6-phosphatase and gluconeogenesis in the perfused liver of the fetal guinea pig. PMID- 6253319 TI - An effect of dexamethasone on glycogen metabolism in hepatocyte cultures. PMID- 6253321 TI - The broad specificity protein phosphatase from mammalian liver. Separation of the Mr 35 000 catalytic subunit into two distinct enzymes. PMID- 6253322 TI - Control of folate deamine activity of Dictyostelium discoideum by cyclic AMP. PMID- 6253323 TI - F0 of Escherichia coli ATP-synthase containing mutant and wild-type carbodiimide binging proteins is impaired in H+ -conduction. PMID- 6253324 TI - Restoration of glucose-induced insulin release in the absence of extracellular calcium by inhibition of the Na+-pump. PMID- 6253325 TI - Phosphorylation of rabbit skeletal muscle phosphorylase kinase by cyclic GMP dependent protein kinase. PMID- 6253326 TI - Differences in the mode of regulation of ornithine decarboxylase activity in undifferentiated versus differentiated mouse N-18 neuroblastoma cells. PMID- 6253327 TI - Effects of vasopressin, glucagon and dibutyryl cyclic AMP on the activities of enzymes of fatty acid esterification in rat hepatocytes. PMID- 6253328 TI - Lantent collagenase from human polymorphonuclear leucocytes and activation to collagenase by removal of a inhibitor. PMID- 6253329 TI - Crosslinking of cytochrome c to peroxidase: covalent complex catalyzes oxidation of cytochrome c1 by H2O2. PMID- 6253330 TI - Ion transport by dog tracheal epithelium. AB - The dog's tracheal epithelium actively transports Cl towards the lumen and Na towards the serosa. In this review the effects of various drugs on these ion transport processes are described and possible mechanisms for Na and Cl transport are discussed. PMID- 6253333 TI - The activity of oxydoreductive enzymes in Balantidium coli. II. PMID- 6253331 TI - Proposed mechanism for neonatal rat tolerance to normobaric hyperoxia. AB - Induction of two forms of superoxide dismutase, catalase and glutathione peroxidase, occurs very rapidly in neonatal rat lung tissue upon exposure of these animals to 94 + % normobaric oxygen. No such oxygen-mediated enzyme induction occurs in the lungs of adult rats. The aged-dependent pattern of enzyme induction correlates with the well-established age-dependent tolerance of neonatal rats to hyperoxia. Enzyme induction occurs in the lungs of neonates in only those species known to be resistant to oxygen-provoked lung damage. Compromise of oxygen-mediated enzyme induction predisposed the neonatal rats to pulmonary oxygen toxicity. These data have formed the basis of the proposal that oxygen induction of the superoxide dismutases catalase and glutathione peroxidase provides a vital part of the defense mechanism against oxygen toxicity. A biochemical mechanism of oxygen-provoked pulmonary damage has been elaborated to explain the role of each enzyme in the protection against oxygen and free radical toxicity. PMID- 6253332 TI - [Reconstruction of the sodium "pump" in plane lipid bilayers. The potentials and problems of the method]. PMID- 6253334 TI - Subcellular distribution of multiple forms of acid p-nitrophenyl phosphatase in rat kidney. PMID- 6253335 TI - Effects of noradrenaline and N6,O2'-dibutyryl 3',5'-cyclic AMP on adipocyte glycerolipid-synthesizing enzymes. PMID- 6253337 TI - In vitro interactions between membrane, hormone, and cyclic nucleotides as revealed with aequorin. PMID- 6253336 TI - Divalent antibodies to mouse embryonal carcinoma cells inhibit compaction in the mouse embryo. PMID- 6253338 TI - cAMP-independent oscillations of adenylate cyclase in Dictyostelium discoideum. PMID- 6253339 TI - Dietary fibre supplementation of a 'normal' breakfast administered to diabetics. AB - The supplementation of a breakfast by 10 g of guar, pectin, agar or locust bean gum in powder form in 13 maturity onset, non-insulin dependent diabetics failed to decrease significantly the post-prandial rise in plasma glucose and insulin seen after a similar meal without the supplement. The values of one hour post prandial increment in blood glucose seen with guar powder were, for control meal (mean +/- SEM) 5.8 %/- 0.4 mmol/l, for test, 5.7 +/- 0.5; with pectin powder, control 6.4 +/- 0.8 mmol/l, test 5.0 +/- 1.2 mmol/l; with agar powder, control 7.5 +/- 1.0, test 7.0 +/- 0.5; with locust bean gum powder, control 5.9 +/- 1.0, test 5.0 +/- 0.7. The equivalent values for one hour insulin (microU/ml, mean +/- SEM) were, for guar powder, 51 +/0 21 and 51 +/- 16; for pectin powder 60 +/- 24 and 63 +/- 17; for agar powder, 27 +/- 9 and 36 +/- 11 and, for locust bean gum powder 53 +/- 26 and 62 +/- 18. The guar, pectin and locust gum tended to form lumps, and all the substances tested were unpalatable in powder form producing feelings of abdominal discomfort and abnormal fullness. Administering the same quantity of guar or pectin in a well hydrated form (but not premixed with the carbohydrate portion of the food) to the same people under identical conditions did not enhance its effectiveness. Supplementing diets with any of these sources of dietary fibre in either of these forms and in these amounts is unlikely to be beneficial in the management of non-insulin dependent diabetes. PMID- 6253340 TI - Insulinotropic effects of hypoglycaemic and hyperglycaemic sulphonamides: the ionophoretic hypothesis. AB - Hypoglycaemic sulphonamides stimulate net uptake of 45Ca++ and insulin release in isolated pancreatic islets. These effects are antagonized by organic calcium antagonists (e.g. suloctidil). In an artificial system, hypoglycaemic sulphonamides, such as gliclazide, stimulate the translocation of calcium into or across a hydrophobic immiscible domain, a process enhanced by the antibiotic ionophore A 23187 and antagonized by suloctidil. In this artificial system, the A 23187-mediated process of calcium countertransport is stimulated by gliclazide and inhibited by diazoxide. It is postulated that the insulinotropic action of hypoglycaemic and hyperglycaemic sulphonamides is primarily attributable to the ionophoretic action of these drugs. PMID- 6253342 TI - Differences in the cyclic AMP-dependent phosphorylation of plasma membrane proteins of differentiated and undifferentiated L6 myogenic cells. AB - Differences in the cyclic AMP-dependent plasma membrane phosphorylation system of undifferentiated and differentiated L6 myogenic cells have been detected. Endogenous plasma membrane protein phosphorylation in undifferentiated L6 myoblasts was stimulated more than three fold by 5 x 10(-5) M cyclic AMP, whereas no statistically significant cyclic AMP-dependent phosphorylation of endogenous plasma membrane proteins was observed in differentiated L6 cells. In undifferentiated cells cyclic AMP promoted the phosphorylation of several proteins, the most prominent of which had a molecular weight of 110,000. In differentiated cells cyclic AMP did not selectively promote the phosphorylation of specific plasma membrane proteins. Both differentiated and undifferentiated L6 cells, however, contain a cyclic AMP-dependent protein kinase capable of catalyzing the phosphorylation of exogenous substrates, such as histone f2b. Therefore, the data show that differentiation in L6 cells is associated with a selective change in the activity of a plasma membrane cyclic AMP-dependent protein kinase which employs endogenous membrane proteins as substrate. PMID- 6253341 TI - Cyclic AMP phosphodiesterase activities in Xenopus laevis oocytes. AB - Cyclic AMP phosphodiesterase activity has been identified in full-grown Xenopus oocytes in vivo and in vitro. About 50% of the in vitro phosphodiesterase activity was present in the solution fraction and 35% in a partially purified membrane fraction. Both activities exhibited high substrate affinity (Km about 10(-6) M). Sucrose gradient fractionation revealed two forms of phosphodiesterase: a 5 S form (peak I) and a 6.5 S form (peak II). Treatment with trypsin led to the activation of the soluble enzyme with the transformation of peak II into peak I. Ethylene glycol bis (beta-aminoethyl ether)-N,N'-tetraacetic acid, calcium dependent regulator, and Fluphenazine did not influence the enzyme activities suggesting that the oocyte phosphodiesterases were not Ca2+-dependent. Intact oocytes were induced to mature by exposure to progesterone; their phosphodiesterase activities and distribution tested in vitro were comparable to those of untreated oocytes. PMID- 6253343 TI - The influence of hormones and other substances on lens regeneration in vitro. AB - Culturing the dorsal iris epithelium of a newt with a pituitary gland in organ culture greatly enhances the ability of the iris epithelium to produce advanced lens regenerates in vitro. In an attempt to elucidate the mechanism by which the pituitary enhances lens regeneration irido-corneal complexes from adult newts were cultured in medium to which various substances had been added either singly or in numerous combinations. Prolactin, insulin, hydrocortisone, and thyroxine failed to enhance the production of advanced lens regenerates in any of the doses or combinations tested. Similarly, addition of 50 microgram/ml of sodium or calcium ascorbate had no effect on the progress of lens regeneration in vitro. Addition of dibutyryl cyclic-AMP caused an inhibition of depigmentation and regeneration at high doses. The results of these experiments show that the effects of the pituitary cannot be duplicated by hormones which other authors have asserted to be beneficial to limb or tail regenerates in vitro. The results with cyclic AMP suggest that prolonged exposure to high doses of cyclic AMP inhibit regeneration and indicate that further studies on the fluctations in cyclic AMP levels throughout the process of lens regeneration must be done. PMID- 6253344 TI - Localization of cyclic nucleotide phosphodiesterase in the multicellular stages of Dictyostelium discoideum. AB - Cyclic 3',5'-adenosine monophosphate (cAMP) is secreted as the chemotactic signal by aggregating amoebae of the cellular slime mold Dictyostelium discoideum. We have used ultramicrotechniques in the biochemical analysis of cyclic nucleotide phosphodiesterase (PD) distribution in individual aggregates at various stages of development. With handmade constriction pipettes in microliter volumes, sections of lyophilized individuals weighing 20-100 ng could be assayed in a reaction coupled to 5'-nucleotidase. Phosphodiesterase activity was measured at pH 7.5 with 12 microM cAMP, cAMP-PD activity in aggregates ranged from 20-40 mmol/h/kg. In the pseudoplasmodium it had dropped to 5-10 mmol/h/kg and a difference in activity between the anterior prestalk cells and posterior prespore cells began to appear. The utmost posterior sections showed elevated phosphodiesterase from this stage onward. During culmination, activity rose to 40-60 mmol/h/kg associated with the developing stalk, while it declined in the spore mass. The papilla remained constant at 5-10 mmol/h/kg. The pattern of localization in the stalk was the same when cGMP was used as substrate. Extracellular phosphodiesterase inhibitor produced at the aggregation stage was found to reduce the localized activity in the culmination stage by 50-80%, with the most marked inhibition occurring in the center of the papilla. We found no evidence of endogenous heat-stable phosphodiesterase inhibitor within the culminating sorocarp. PMID- 6253345 TI - Mammary tumor virus antigen expression in inbred mouse strains of European origin established in Japan. AB - Expression of the mammary tumor virus (MTV) antigen in the milk from inbred mouse strains maintained in Japanese laboratories was investigated by means of the immunodiffusion test (ID) and the results were compared with the incidence of mammary tumors in breeding females of identical strains. Japanese strains tested were classified into two groups. The DD/Tbr, DDD and KF strains were derived from "dd" stock mice, and they showed equally high incidences of MTV antigen expression in the milk, though each strain developed mammary tumors with different incidences; 71%, 14% and 22%, respectively. Other strains originated from Swiss albino mice. The incidence of MTV antigen expression in the milk of SHN and SLN strains was the same as that of mammary tumors at an early age. PMID- 6253346 TI - Lymphoproliferative response to membrane extracts of nasopharyngeal carcinoma. AB - The tumor-associated antigen (TAA) was extracted from cultured cells obtained from nasopharyngeal carcinoma (NPC), and the specific immune reaction was studied by utilizing the proliferation reaction of lymphocytes from NPC patients. The following results were obtained. (1) The stimulation of lymphocytes by membrane soluble antigen (MS-Ag) was significantly different in the group of patients with NPC and the control groups (patients with malignant tumors of the head and neck and healthy individuals). Lymphocytes from the NPC patients gave a significantly higher stimulation index (SI) value with NPC MS-Ag, but a lower value with PHA, as compared with those of normal controls. (2) No definite correlation was observed in anti-Epstein-Barr virus (EBV) antibody titers. (3) As for the correlation with various histological types, apparently enhanced reaction was noted irrespective of the histological type of the cancer. (4) In connection with stage classification, the reaction was always negative in patients in stage IV. A particularly close correlation was noted between the degree of the response and the N classification. Some inhibitory factor affecting the LP reaction might appear with the progress of N and M. PMID- 6253347 TI - Functional responsiveness of an isolated and enriched fraction of rodent gastrin cells. PMID- 6253348 TI - Clinical conference. Hormonal diarrhea due to pancreatic tumor. PMID- 6253349 TI - HLA antigens and hepatocellular carcinoma. PMID- 6253350 TI - [The spiritual bond in nature; mathematico-musical acoustics as a structured analytic method. VI. Biology]. PMID- 6253351 TI - [Structure and innervation of the abdominal stretch receptors in the crayfish Orconectes limosus (Raf.)]. PMID- 6253352 TI - Restriction endonuclease mapping of ColE2-P9 and ColE3-CA38 plasmids. AB - Using single and double restriction-endonuclease digestions, 16 and 17 cleavage sites have been mapped for the ColE2-P9 and ColE3-CA38 plasmids, respectively. One or more sites for AvaI, BglI, EcoRI, HincII, PvuI, PvuII, SmaI and XhoI endonucleases were found in both plasmids, two BglII sites were found only in ColE2-P9, and one KpnI site was unique to ColE3-CA38. ColE2-P9 was found to be slightly smaller than ColE3-CA38, 4.4 Md compared to 4.6 Md. Eleven restriction sites are common to both plasmids in that they are identically placed relative to each other. These sites define a continuous DNA segment equal to over 60% of each plasmid. The remaining portions of the plasmids, which contain the non-homologous regions identified by Inselburg and Johns (1975) have no restriction sites in common, and differ in size by about 0.2 Md. PMID- 6253353 TI - Direct repetition of a 1.2 Md DNA sequence is involved in site-specific recombination by the P1 plasmid R68. AB - R68.45, a mutant R68 plasmid, carries a 1.5 Md DNA insertion near its kanamycin resistance region. This DNA consists of a 1.2 Md DNA repetition of neighbouring R68-DNA and a 0.3 Md "foreign" DNA fragment that is flanked by this direct DNA repeat. This fragment seems to be involved in the formation of R'68.45 plasmids. Duplication of the 1.2 Md DNA sequence is also involved in site-specific recombination events of RP4. This 1.2 Md DNA fragment has the properties of an IS sequence and is denoted IS8. PMID- 6253354 TI - IS-like element IS8 in RP4 plasmid and its involvement in cointegration. AB - The structure of the cointegrate plasmids formed by fusion of RP4 and the tumour inducing plasmid (pTi) of Agrobacterium tumefaciens was analyzed. In all of the nine independently isolated pTi::RP4 cointegrates, the integration occurred at the same site on the RP4 genome. Moreover, a 1.2 Md (1750 bp) RP4 sequence (IS8) was directly repeated at both junction sites of the two replicons. The insertion of RP4 generated deletions, starting from the IS8 sequence and extending into the Ti part of the cointegrate. Dissociation of the cointegrates resulted in wild type RP4 and Ti-plasmids with the IS8 sequence inserted at the original RP4 insertion site. The processes of integration and dissociation and the genetic properties of the cointegrates indicate that the IS8 sequence has unique characteristics defining a new insertion sequence. PMID- 6253355 TI - EcoRI-generated reiterated components of the rat genome. I. Sequence of two (92 and 93 bp) related DNA fragments. AB - The sequence of the 92 and 93 bp long, highly repetitive DNA fragments, isolated from EcoRI digested rat liver DNA, were determined. These fragments, designated 92 and 93, are found in equal abundance, 6.5 x 10(5) copies per haploid genome. J92 and J93 can be distinguished by their differential sensitivity to cleavage by HaeIII and HindIII, respectively, which cut the fragments at 75 and 57 bp from their mutually homologous 5'-ends. J92 and J93 are 38% and 35.4% G + C, respectively, and contain a disproportionate number of triplets complementary to stop codons in all reading frames. Three methylated sites were found in J92 while none could be detected in J93. The sequences around the m5C sites were 5'-Py-Py m5C-G-Pu-Pu, except for one case where the second Py was replaced by an A. This site appeared to be hemimethylated. When J92 and J93 are placed in register from their mutually homologous 5'-ends, homology is 73% for the first 30 bp region and 63.5% for the total molecule. Thermal melting studies indicate sequence heterogeneity within J92 and J93 from substantial internal base mismatches. The sequences derived are therefore composite averages for the whole molecules. The Cot1/2 for the sequence was measured spectrophotometrically to be 2 x 10(-2) M/s on a DNA phosphorus basis and 2.15 x 10(-4) M/s on a mole fragment basis. PMID- 6253356 TI - Expression of a foreign eukaryotic gene in Saccharomyces cerevisiae: beta galactosidase from Kluyveromyces lactis. AB - Three recombinant DNA vectors carrying the beta-galactosidase structural gene, LAC4, from the yeast Kluyveromyces lactis were constructed and transformed into Saccharomyces cerevisiae. All transformants expressed the beta-galactosidase activity of LAC4. However, the level of enzyme activity varied, being highest in cells transformed with vectors which are maintained as multicopy plasmids and lowest in cells transformed with a vector which integrates into chromosomes. Enzyme levels probably reflect gene dosage. LAC4 is very stable when integrated into a chromosome, but unstable when carried on a plasmid. Therefore, stability is a property of the recombinant vector rather than of LAC4, LAC4-coded beta galactosidase synthesized in either S. cerevisiae or in K. lactis is the same as judged by two-dimensional polyacrylamide gel electrophoresis. However S. cerevisiae transformed with LAC4 cannot grow on lactose, probably because lactose does not enter the cell. PMID- 6253357 TI - Identification of palindromic sequences recognized by restriction endonucleases, as based on the tabularized sequencing data for seven viral and plasmid DNAs. AB - Computer search of DNA sequences for phages phi X174, G4, M13 and fd, plasmids pBR322 and pAO3, and virus SV40, was employed to prepare tables specifying the size classes and frequencies of DNA segments located between all possible tetra-, penta- and hexanucleotide palindromes. As described earlier (Fuchs et al., 1978), these tables permit identifying sequences recognized by most of the restriction endonucleases. The effect of sequencing errors on the accuracy of the present identification method is evaluated. Only four of the 224 listed sequences do not appear in any of the seven DNAs, leading to discussion (see Appendix) on the natural sequence distribution. PMID- 6253358 TI - On the distribution of the nucleotides in seven completely sequenced DNAs. AB - Several Markov chain models (up to fourth order) have been fitted to the sequences of the seven DNAs presented in Fuchs et al. (1980). Two methods for determining the order of Markov chain are applied to the data. The two methods lead to different conclusions and we discuss these discrepancies. When the distribution of the nucleotides in a DNA sequence is investigated, it is suggested that the study on the order of the Markov model should be supplemented with additional analysis. PMID- 6253359 TI - Changes in the NIH Guidelines for Recombinant DNA Research (Appendix 3: September 1979--April 1980). PMID- 6253360 TI - [Study of the functional state of a peripheral nerve and neuromuscular junction as a criterion for setting health standards for chemical substances]. PMID- 6253361 TI - [Diagnosis and treatment of trophoblastic tumor in the light of current theories]. PMID- 6253362 TI - Pathogenesis of necrotising enteritis with special reference to intestinal hypersensitivity reactions. AB - The aetiological aspects of 83 sporadic cases of necrotising enteritis (NE) have been studied. Of 56 cases in which histology of the intestine was possible, eight showed appearances (oedema and local eosinophilia) suggestive of a type I hypersensitivity reaction, while in 37 the appearances were suggestive of a type III reaction. We suggest that these reactions, which were more common in children and young adults, were initiating factors in the intestinal necrosis. The type III reactions (submucosal arteritis, fibrinoid necrosis of arteriolar walls, intramural and perivascular infiltration with polymorphonuclear, mononuclear, and eosinophil cells, and submucous oedema) were in seven cases accompanied by extraintestinal lesions (hypercellularity of glomeruli, amorphous material in the Bowman's capsular space, tubular casts, mononuclear cell infiltration into the hepatic portal tracts, congestion and oedema of the lung) which were compatible with systemic immune complex disease. The mesenteric lymph nodes in 12 out of 15 cases with intestinal arteritis showed appearances indicative of a humoral immune response. We suggest that NE is a two-stage process. In stage 1, a necrotic focus is established in the intestinal mucosa-submucosa by 'initiating' factors of vascular (functional or organic) or microbial (exotoxic, endotoxic, or Shwartzman) origin. Functional circulatory insufficiency in the intestine is of particular relevance to necrotising enteritis in neonates and in adults with traumatic shock or cardiac insufficiency. The jejunal and--to a lesser extent- the ileal microcirculation appear to be particularly vulnerable to microcirculatory insufficiency. Ninety-seven per cent of our cases were of NE of the small intestine of which 76% involved the jejunum alone or as a part of a jejunoileitis. These 'initiating' factors act either singly or synergistically with 'promoting' factors (changes in the volume, composition, or pH of the diet, intestinal stasis, or bacterial factors) in the establishment of necrotic foci in the intestine. Stage 2 results from the colonisation of the necrotic foci by intestinal clostridia, the toxigenic capacity of which will determine the progress of the intestinal lesion. Clinically established NE is essentially gas gangrene of the intestinal wall. Our bacteriological findings (microscopic, cultural, and serological) support a pathogenetic role of Cl. welchii in the established stages of necrotising enteritis. Strains of Cl. welchii from NE cases had significantly higher histidine decarboxylase activity than strains from control sources; it is possible that the resultant histamine production could act as a promoting factor in stage 1. Neutralising antibody against the Wanowrie virus, an Asian arbovirus which produces haemorrhagic enteritis in mice, was absent in the paired sera from 10 cases examined. PMID- 6253363 TI - Comparative absorption of vitamin D3 and 25-hydroxyvitamin D3 in intestinal disease. AB - The absorption of simultaneously administered equimolar doses of 14C vitamin D3 and 3H 25 hydroxyvitamin D3 (25-OH-D3) has been studied in controls and patients with a variety of gastrointestinal disorders. As assessed from peak radioactivity in the serum and from faecal excretion of radioactivity, malabsorption of both vitamin D3 and 25-OH-D3 occurred in patients with steatorrhoea. Malabsorption of vitamin D3 was greater than 25-OH-D3. The magnitude of malabsorption of these compounds was related to the severity of the steatorrhoea but was moderate enough to suggest that replacement therapy in patients with intestinal malabsorption should be accomplished with relatively small doses of vitamin D. The more potent vitamin D metabolites are probably unnecessary in this situation. PMID- 6253365 TI - [Calcium pyrophosphate dihydrate deposition disease]. PMID- 6253364 TI - Possible role of a defect in hepatic bilirubin glucuronidation in the initiation of cholesterol gallstones. AB - Abnormally low activity of hepatic bilirubin UDP-glucuronosyltransferase was found in 25% of 81 unselected patients with gallstones, as compared with only 3% in 35 controls. At the time of cholecystectomy, the stones were taken for analysis in 48 of 81 patients, and a bile sample was obtained in 42 of them. Among the stones, 75% were cholesterol stones, 15% pigment stones, and 10% 'intermediate' stones. Low hepatic conjugating activity was not preferentially associated with a given type of stone. No relation was found between the enzymic deficiency and the biliary cholesterol saturation index. A high proportion of biliary bilirubin monoglucuronide (over 40%) was found in four of seven patients with low transferase activity, as was earlier demonstrated in patients with overt Gilbert's syndrome. Raised biliary bilirubin monoglucuronide was also found in three patients, out of 46, who had normal transferase but raised biliary beta glucuronidase activity. There was no evidence that deficient bilirubin conjugation could be a consequence of gallstones: the activity of another hepatic microsomal enzyme, glucose 6-phosphatase, taken as a reference, was measured in 12 patients and was always normal. Taking into account the very high frequency of a bilirubin centre in the cholesterol stones (87% of the cases in the present series), it is suggested that the increased proportion in poorly soluble biliary bilirubin monoglucuronide, which was associated with defective conjugation, could act as a trigger for gallstone initiation, regardless of the final composition of the stone. PMID- 6253366 TI - Detection of mouse ectromelia virus using the heterologous rabbit antiserum conjugated with fluorescein isothiocyanate. PMID- 6253367 TI - [Pharmaco-angiography of liver tumours (author's transl)]. AB - In 36 patients with clinical suspicion of liver tumours, pharmaco-angiography using adrenalin was added to the usual liver arteriography. In 31 of these patients rumour involvement of the liver was confirmed by surgery, laparoscopy or autopsy. In four out of ten patients with benign liver tumours, pharmaco angiography lead to improved demonstration and therefore classification of the tumour. Four out of seven malignant primary tumours. Four out of seven malignant primary tumours of the liver were also better demonstrated by pharmaco angiography. Amongst 14 patients with liver metastases, an improvement in the angiographic demonstration by pharmaco-angiography was achieved in nine. This was particularly the case in tumours showing tumour vessels. Neither benign nor malignant tumours showed constriction of their vessels as a result of pharmaco angiography and this is therefore not able to differentiate between these. It was also found that tumours showing the the same histology could behave differently during pharmaco-angiography. PMID- 6253368 TI - [The radiation dose to children bone scintigraphy with 99mTc-phosphate compounds (author's transl)]. AB - In order to determine the radiation dose to children during bone scintigraphy, distribution and excretion measurements on 99mTc-pyrophosphate and 99mTc diphosphonate were carried out in rats, piglets, children and adults. Because of the more intensive bone metabolism in children, uptake of 43 to 47% is higher than in adults, in whom uptake in the skeleton reaches 33 to 36%. Assuming homogenous distribution of uptake, radiation dose to the skeleton in children of the ages investigated was 51 to 55 mrd per mCi. Bearing in mind the non homogeneous distribution in the juvenile skeleton, radiation dose at growth point reaches 85 to 95 mrd per mCi. PMID- 6253369 TI - [Diet planning for hypertensive patients (1800 calories/day). Daily planning for the treatment of hypertension by means of a low sodium, fiber and polyenic acid rich diet]. PMID- 6253371 TI - [Malignant melanomas of the skin. Early diagnosis and differential diagnosis.- conclusion]. AB - Amelioration of prognosis in cutaneous malignant melanomas essentially depends on early diagnosis which necessitates the knowledge of some risks and clinical signs of malignancy. The clinical and also histological items of lentigo maligna melanoma, superficial spreading melanoma, acro-lentiginous melanoma and nodular melanoma are referred in detail. Hints are given at the precursor lesions as well as the early signs of malignancy. For differential diagnosis, eight kinds of relatively frequent pigmented skin lesions are discussed. PMID- 6253370 TI - [Immunosuppressive treatment im multiple sclerosis]. AB - The results of various uncontrolled trials of immunosuppression in the treatment of multiple sclerosis have indicated an amelioration in the clinical course of the disease in about half of the treated patients. These observations have recently been confirmed by the findings in a double blind controlled study. The aim of future clinical trials has to lay in increasing the efficacy of conventional immunosuppressive agents in the treatment of multiple sclerosis. Further progress in immunological research and a better understanding of the etiology of multiple sclerosis may allow one day a more specific immunotherapy with the help of immunoregulatory substances. PMID- 6253372 TI - Hormone responsiveness of the lipoma: a tumor of adipose tissue. AB - The ability of adipocytes from lipomas to respond to lipolytic stimuli was investigated to determine whether diminished responsiveness could account for the excessive accumulation of neutral lipid which characterizes these tumors. Baseline studies were performed on rat adipose tissues to determine optimal conditions for comparison of lipolytic responses to a variety of hormones. Cell concentrations, the specific depot site from which the cells are derived, the age of the animal and the tissue preparation, as to whether fragments are used as opposed to collagenase-treated isolated cells, were determined to affect the lipolytic response. When the response of lipomata adjusted per unit cell (DNA) are compared to unaffected cells adjoining the tumor, an enhanced lipolytic respnse to microM concentrations of l-epinephrine is seen in both fragments and isolated cells. These findings indicate that diminished lipolysis cannot account for the exaggerated storage of neutral fat in these tumors. PMID- 6253373 TI - Effect of a synthetic substituted alpha 1-18 ACTH on mineralocorticoid secretion. PMID- 6253374 TI - Suppression by adrenalectomy of the early stimulation of rat kidney gluconeogenesis during acute liver intoxication. PMID- 6253375 TI - Isolation and characterization of acylneuraminate cytidylyltransferase from frog liver. AB - Frog liver (Rana esculenta) is a rich source of acylneuraminate cytidylyltransferase. The soluble enzyme was purified 250-fold almost to purity with 25% yield and a specific activity of 9 mkat/kg protein (0.54 U/mg protein) using DEAE Sephadex and Sepharose 6B chromatography, followed by preparative polyacrylamide gel electrophoresis. The molecular weight of the cytidylyltransferase was determined to be 163 000 with the aid of Sepharose 6B chromatography and gel electrophoresis, with or without dodecyl sulphate or urea. No subunits were found. The isoelectric point of the enzyme is at pH 6. Optimum reaction rate was observed at pH 9, 37 degrees C, 50mM Mg2 or Ca2 and ImM mercaptoethanol. The Km values for N-acetylneuraminic acid, N-glycoloylneuraminic acid and CTP are 1.6mM, 2.3 mM and 0.6mM, respectively. O-Acetylated sialic acids are inactive with the cytidylyltransferase from frog liver. Enzyme activity can be inhibited by SH reagents and CMP (Ki = 0.5mM). PMID- 6253376 TI - [1H-NMR-spectroscopic evidence for the release of N-acetyl-alpha-D-neuraminic acid as the first product of neuraminidase action (author's transl)]. AB - The 1H-NMR spectroscopy was used to study the anomeric configuration of N-acetyl D-neuraminic acid released by the action of neuraminidase. The hydrolysis of NeuAcalpha 2 leads to 3 Gal-beta 1 leads to 4Glc (20mM) by the enzymes of Clostridium perfringens and Arthrobacter ureafaciens (50 mU, 150 mU and 800 mU, respectively) in 50mM Na/K-phosphate buffer pD 5.4 was observed by recording the spectra. On the basis of the characteristic signals of the protons at C-3 (alphaNeuAc: delta[H(3e)] = 2.72, delta[H(3a)] = 1.64; betaNeuAc: delta[H(3e)] = 2.25, delta[H(3a)] = 1.84) the product of the enzymatic cleavage was identified to be the N-acetylneuraminic acid in the alpha-anomeric form. Two hypotheses are discussed to explain how the enzymatic hydrolysis may occur and how N-acetyl alpha-D-neuraminic acid leaves the catalytic site of the neuraminidases with retention of the C-2 configuration. PMID- 6253377 TI - Studies in vitro on the biosynthesis of ceramide and sphingomyelin. A reevaluation of proposed pathways. AB - The postulated biosynthetic-pathways of ceramide and sphingomyelin were reinvestigated in extensive investigations by means of synthetic stereo- and radio-chemically pure substrates of high specific radioactivity. As a result, the synthesis of ceramides requires the acyl-CoA-mediated acyltransfer to the long chain bases sphingenine and sphinganine. During the biosynthesis of sphingomyelins, phosphocholine is being transferred from the donor CDP-choline to the primary alcohol group of ceramides. Neither can the free long chain sphingosine bases act as acceptor molecule for the phosphocholine group from CDP choline, nor has a transfer of [N-14CH3]phosphocholine from [N-14CH3]phosphatidyl choline to ceramide by rat liver enzyme preparations been observed. In agreement with previous studies in vivo, the acylation of sphingenylphosphocholine by acyl CoA or free fatty acid, ATP and CoASH as an alternative pathway in sphingomyelin biosynthesis has been excluded. Other parameters of the CDP-choline:ceramide cholinephosphotransferase reaction (pH-optimum, ion requirement, competitive inhibition by diacyl glycerols, chain length of fatty acids) are reported. Sphingenine-containing ceramide species are preferred as acceptor molecules. Ceramide species with the L-threo (2S,3S)-enantiomeric long-chain bases are better acceptors than the corresponding D-erythro (2S,3R)-isomeric compounds. The meaning of the steric arrangement for the reaction is discussed. PMID- 6253378 TI - Benign and low grade variants of mixed Mullerian tumour of the uterus. AB - The clinico-pathological features of 11 examples of a rare group of uterine neoplasms composed of both epithelial and stromal components are reported. The patients complained of abnormal vaginal bleeding or discharge. Two of the tumours arose in the cervix, seven in the endometrium and two from both, forming large polypoid masses projecting from the cervix and/or filling the uterine cavity. Microscopically, the epithelial elements ranged from benign to adenocarcinoma. A similar range of stromal elements was also seen, varying from entirely bland to low grade to high grade sarcoma. The variable histology of the tumours is reflected in their biologic behaviour. Of the three tumours with the highest histological grade of malignancy, one recurred and killed the patient. One tumour, in which both components were regarded histologically as benign, recurred twice before hysterectomy. Our findings lend support to the concept that these tumours are variants of mixed Mullerian tumour. We advocate the acceptance of the latter term so that all grades of this tumour can be accommodated under one designation. PMID- 6253379 TI - Cholangiocarcinoma coexisting with developmental liver cysts: a distinct entity different from liver cystadenocarcinoma. AB - We report one liver cystadenocarcinoma and two cholangiocarcinomas coexisting with developmental liver cysts. The cystadenocarcinoma was a solitary multilocular cyst with histological features similar to those seen in ovarian mucinous cystadenocarcinoma. In contrast, the other two tumours were a mixture of solid adenocarcinoma and multiple non-neoplastic cysts containing serous fluid and lined mainly by atrophic epithelium. In both these cases renal cysts were also present and in one case there was focal malignant change of the epithelium lining the cysts from which the solid adenocarcinoma could have originated. Our observations support the view that cholangiocarcinoma associated with developmental liver cysts is an entity different from liver cystadenocarcinoma. PMID- 6253380 TI - Sweat-gland carcinomas: prognosis related to histological type. AB - A series of 10 sweat-gland carcinomas is reported. The ages of the patients at presentation ranged from 12 to 79 years. Three of the tumours had shown long latent periods with a mass present for up to 20 years. Prognosis proved to be related to the histological subtype. Thus, two papillary syringocystadeno carcinomas, one recurring cylindroma, one hybrid cylindroma/adenoid cystic carcinoma and two mucoid carcinomas were apparently all cured by surgery. Two mucoepidermoid carcinomas and one histologically malignant chondroid syringoma were not only histologically, but also clinically, malignant. The last case, a chondroid syringoma of benign histology, proved nevertheless to be malignant clinically. PMID- 6253381 TI - The pathology of the liver in porphyria cutanea tarda. AB - We report the findings in 53 biopsies from 45 patients with porphyria cutanea tarda (PCT). Red autofluorescence and birefringent acicular cytoplasmic inclusions were constant findings in all untreated cases. Autofluorescence occurs in other hepatic porphyrias, but acicular inclusions appear to be specific for PCT; we have seen them in subclinical porphyria and before development of cutaneous symptoms. They are probably uroporphyrins and they trend to disappear during rinsing by water during most staining procedures. We recommend unstained paraffin sections for their demonstration. Liver damage in PCT has features distinct from other liver diseases, including alcoholic liver disease. These include constant but mild periportal siderosis, focal lipofuscin deposition, focal lobular hepatocyte necrosis associated with groups of pigment-laden macrophages, focal steatosis, marked hepatocyte hyperplasia and the presence of periductal lymphocyte aggregates. The latter have not been previously described in PCT and were present in 43% of our cases. There is a direct relationship between increasing age and progressive distortion of liver architecture, with fibrosis present at a mean age of 48 years, cirrhosis at 57 and hepatocellular carcinoma at 66. The characteristic liver histology and the natural history of PCT are against this being the result of any non-specific liver damage and favour instead a specific liver disease whose pathogenesis may be mainly the result of the metabolic defect of PCT. PMID- 6253382 TI - Mucus-secreting 'alveolar-cell' tumour of the lung: a histochemical comparison of tumours arising within and outside the lung. AB - Five cases of mucus-secreting 'alveolar cell carcinoma' are described, two of primary pulmonary origin and three metastatic from breast or pancreas. Mucin histochemistry demonstrated qualitative and quantitative differences between the mucopolysaccharides produced by these two groups of tumours. Hyaluronic acid production was restricted to the primary lung tumours. Greater quantities of acid sulphomucins were found in the two tumours arising in the lung and more neutral mucins in the three tumours metastatic from extra pulmonary primaries. It is proposed that mucus-secreting alveolar cell carcinomas represent an unusual, and saprophytic relationship between the metastatic cells of well-differentiated adenocarcinomas and the lung. As the malignancy of the tumour cells increases, so the ability to produce specific mucins decreases and, simultaneously, the tumours cease to maintain their alveolar pattern. PMID- 6253383 TI - Hepatocellular carcinoma and hepatitis B. PMID- 6253384 TI - Short-term inpatient care and readmission rates: the CMHC approach versus the private approach. AB - Community mental health centers hospitalize patients for a significantly shorter time than do private psychiatric hospitals. Proponents of the private system of care assert that the shorter hospitalization contributes to an increased probability of readmission. A comparison of the readmission experience of CMHC patients and private patients who were hospitalized at the same institution showed no significant differences in the short-term recidivism rate. It is suggested that an aftercare network that is closely integrated with hospital care is a necessary supplement to brief hospitalization. In addition, it appears that restrictive reimbursement policies for outpatient care result in an increase in the duration of hospitalization and in the probability of rehospitalization. PMID- 6253385 TI - An agency model for developing and coordinating psychiatric aftercare. AB - The development of coordinated systems for delivery of aftercare services to psychiatric patients has lagged far behind the theoretical emphasis on community maintenance. From a collaboration of 29 treatment and rehabilitation facilities, an independent agency was established to improve aftercare services in Metropolitan Toronto. Known as Community Resources Consultants, the agency was designed to facilitate and rationalize the use of existing services, to identify gaps in service, to initiate or cooperate in the development of new services, and to involve hospital and community service personnel in raising the level of expertise in the provision of aftercare. Formal and informal assessments indicate that CRC has had a positive effect on the provision of aftercare services and on professionals' level of awareness of aftercare priorities. PMID- 6253386 TI - Phagocytic tumor cell activity in oat cell carcinoma of the lung. AB - Biopsy specimens from 14 patients with oat cell carcinoma of the lung metastatic to bone marrow and from one patient with a localized tumor were examined for evidence of phagocytic activity by tumor cells. Phagocytic activity was observed in tumor cells in 90 per cent of the bone marrow biopsy specimens, 90 per cent of the cytology specimens, and 70 per cent of the biopsy specimens of other tissues. The cell most often phagocytosed was the leukocyte. Seventeen other tumors metastatic to bone marrow were studied and only one evidenced phagocytic activity. PMID- 6253388 TI - Histamine regulates lymphocyte mitogenic responses through activation of specific H1 and H2 histamine receptors. AB - In previous studies we have reported that patients with mild atopic eczema have enhanced lymphocyte mitogenesis while those with severe disease have markedly suppressed responses. Similarly, histamine in low concentrations enhanced mitogenesis while higher levels inhibit mitogen stimulated thymidine uptake. In the present study, we investigated the kinetics of this response and the interaction of histamine with its cell-surface receptors on lymphocytes. Histamine (10(-3) M) markedly inhibited [3H]-thymidine incorporation to 27% of control levels when added at the beginning of a 72 h culture period. When added after 24 and 48 h of culture, however, the suppression was much less (62 and 88% of control). Lymphocyte cultures pulsed for 1 h with histamine, washed free of the agent and then cultured with mitogen also showed marked suppression of [3H] thymidine uptake. The kinetics of the response suggest that histamine acts to inhibit initial processing or recruitment steps in the mitogenic assay. Cimetidine, an H2-receptor blocking agent, prevented the suppressive effect of high levels of histamine while diphenhydramine, an H1 blocker, abolished the enhancement observed with low levels. Pre-incubation of mononuclear cell suspensions, which has been shown to decrease suppressor activity, resulted in a decreased response to added histamine. This change in histamine responsiveness was associated with an alteration in H1:H2 histamine binding as determined with a radiolabelled ligand-binding assay. Histamine suppression of mitogenesis was associated with an increase in cellular cAMP levels while enhancement was accompanied by a small increase in cGMP. These data suggest that lymphocyte function may be regulated, in part, by histamine receptor bearing cells with H1 stimulation having a role in enhancement of mitogenesis and H2 stimulation resulting in normal suppressor activity. PMID- 6253387 TI - Whither monoclonal antibodies? PMID- 6253389 TI - Cellular and humoral immune responses to buffalopox virus in experimentally infected mice and rabbits. AB - The experiments on protective immunity were conducted in a closely bred population of mice which did not show graft versus host reactions. Simultaneous passive transfer of 0.25 ml rabbit anti-buffalopox virus serum and subsequent challenge with 0.05 ml 10(5) TCID100/ml of buffalopox virus (BPV) showed 57.15 and 47.06% protection with a 1:2 and 1:16 dilutions of buffalopox hyperimmune serum 24 h prior to challenge with BPV showed 87.50 and 75.0% protection, respectively. The passive transfer of normal saline or normal rabbit serum did not protect mice against lethal challenge with BPV. The protection conferred by 5.0 x 10(6) and 15.0 x 10(6) spleen cells obtained from immune donor mice was 37.5, 42.85 and 50.0%, respectively. None of the mice that received spleen cells obtained from donors immunized with normal saline emulsified in Freund's incomplete adjuvant survived lethal challenge with BPV. T- and B-cell levels in the peripheral blood of rabbits during the course of BPV infection revealed transient relative lymphopaenia on the 4th, 5th and 7th days post infection. These values returned to normal on the 14th and 21st days post infection. No marked difference in percentage of B cells or absolute B-cell number between control and infected rabbits was found. This study revealed that both cellular and humoral immunity seem to play a role in recovery from BPV infection in mice and rabbits. PMID- 6253390 TI - Chemoarchitectonics of the brain stem reticular nuclei of the microchiropteran bat Taphozous melanopogon Temminck. PMID- 6253391 TI - Pathology of Nephrosis-nephritis in chickens experimentally induced by infectious bursal disease virus. PMID- 6253392 TI - Generation of a chemotactic lipid from a arachidonic acid by exposure to a superoxide-generating system. AB - Certain products of arachidonic acid have been demonstrated recently to possess chemotactic activity for human polymorphonuclear leukocytes (PMN). Enzymatic (lipoxygenase, cyclooxygenase) generation of these lipid chemotaxins proceeds through the formation of intermediate lipid peroxides. Since lipid peroxidation can be mediated by oxygen-derived free radicals, we have examined whether chemotactically active products of arachidonic acid could be produced by exposing this unsaturated fatty acid to a superoxide-generating system. A lipid with potent chemotactic activity for human PMN was produced by incubating arachidonic acid with xanthine oxidase and acetaldehyde. Generation of chemotactic activity was time-dependent and could be inhibited to the greatest extent by scavengers of singlet oxygen (i.e., histidine, uric acid, and 2,5-dimethylfuran). Inhibition was also observed with scavengers of superoxide anion radicals (i.e., superoxide dismutase), hydrogen peroxide (i.e., catalase), and hydroxyl radicals (i.e., mannitol). Silica gel thin-layer radiochromatography demonstrated a single peak with chemotactic activity (Rf = 0.33-0.38) distinct from unaltered arachidonic acid. The product of arachidonic acid was chemotactic at a concentration of 3.0 ng/ml and chemokinetic at concentrations of 0.75-1.5 ng/ml. Since PMN produce oxygen-derived free radicals and singlet oxygen upon stimulation of their plasma membrane, and since arachidonic acid is widely distributed in human tissues, free radical-mediated generations of chemotactic activity from arachidonic acid may play an important role in amplifying inflammatory responses. PMID- 6253393 TI - [Metabolic studies on intensive care patients during gastric tube feeding with a formulated diet, rich in bulk]. AB - Results of metabolic investigations in 5 intensive care patients fed via gastric tube with a prefabricated formula diet (based on milk protein, rich in bulk material) are reported. Clinical handling proved to be rather simple, due to the homogeneity of the mixture tube, obstruction never occurred. Tolerance of the tested tube feeding was good in 4 of 5 patients (in 1 tetanus patient the study to be interrupted because of acute abdominal symptoms), mean body weight increased. During the 10-day treatment period, a slightly positive nitrogen balance (mean 1.4 +/- 5.9 g/day) resulted in a cumulative nitrogen retention of 15.5 g. Fat losses in faeces, probably due to high intake (more than 50% of calories administered), were moderately elevated compared to normal values; in some patients decreased fat resorption with steatorrhoea was observed on various days. The formula diet under investigation may be qualified as a suitable nutritional regime for intensive care patients with intact gastrointestinal function. In cases with impaired fat utilization, however, relative calorie deficiency interfering with protein synthesis (gluconeogenesis) might occur. Lowering of the fat quota (having been taken into account in the meantime) to the benefit of elevated carbohydrates may be desirable in this context. PMID- 6253394 TI - Leukemogenesis, immune responsiveness, and murine leukemia virus expression in congenic AKR/J mice differing at H-2. AB - In this study we examined the leukemia incidence, ectropic and xenotropic murine leukemia virus expression, and immune responsiveness of congenic AKR/J mice differing at the H locus. Congenic AKR.L-H-2b/1 mice, bearing the H-2b haplotype derived from C57L/J, were found to have a significant delay in time of death due to leukemia relative to that of AKR/J (H-2k) mice. The expression of ecotropic murine leukemia virus was found to be identical in both strains. The expression of xenotropic murine leukemia virus did vary, however, with the AKR.L-H-2b/1 mice showing a significantly reduced level of virus expression relative to AKR/J mice. In addition to these observations, we found that the AKR.L-H-2b/1 mice have an enhanced blastogenic responsiveness to phytohemagglutinin and to specific antigen to which they had previously been sensitized. Concomitant enhanced antibody response was not found. We suggest that the stronger cellular response, relative to AKR/J, may contribute to the delay in leukemia onset and to reduced xenotropic virus expression observed with the congenic mice. PMID- 6253395 TI - Antivirus antibody-dependent cell-mediated cytotoxicity during murine cytomegalovirus infection. AB - BALB/c mice infected with murine cytomegalovirus were studied to determine whether antibody-dependent cell-mediated cytotoxicity contributes to the immune control of this infection. Antibody-dependent killer cells from uninfected mice were used as effector cells to assay for antibody in sera of infected mice. Secondary immune sera were found to contain both cytomegalovirus-specific and autoreactive antibodies. After primary infection only cytomegalovirus-specific antibodies were found. These were detected by antibody-dependent cell-mediated cytotoxicity within 8 to 10 days after onset of infection, but usually not until day 21, by a neutralizing antibody assay. Antibody titers were about 10-fold higher by antibody-dependent cell-mediated cytotoxicity than by neutralization. The results indicate that cellular immunity to cytomegalovirus infection includes an antibody-dependent cell-mediated cytotoxicity response which is likely to be highly efficient and may contribute significantly to control of both acute and later stages of infection. PMID- 6253396 TI - Attachment of SA-11 rotavirus to erythrocyte receptors. AB - Treatment of human group O and sheep erythrocytes with receptor-destroying enzyme rendered them inagglutinable by simian rotavirus SA-11. The erythrocyte receptors were also removed by periodate oxidation and markedly reduced by incubation with a high concentration of trypsin, but they were not altered by infectivity enhancing concentrations of trypsin, p-hydroxymercuribenzoate, or sodium sulfite (Na2SO3). Hemagglutinating activity of the virus particles was destroyed by periodate oxidation at 37 degrees C, p-hydroxymercuribenzoate, and a high concentration of trypsin and decreased by Na2SOa but was not altered by incubation with receptor-destroying enzyme, infectivity-enhancing concentrations of trypsin, or periodate oxidation at 4 degrees C. These results indicate that neuraminic acid-containing receptor substances are involved in the interaction of the virus with human and sheep erythrocytes, and suggest that SA-11-erythrocyte union involves carbohydrate on the surface of erythrocytes but not on the virion. Sensitivities of the SA-11 hemagglutinin to alcohols and repeated freeze-thaw cycles were also investigated. PMID- 6253397 TI - Replication of murine cytomegalovirus in lung macrophages: effect of phagocytosis of bacteria. AB - Murine cytomegalovirus was found to replicate in lung and peritoneal macrophages of both CF-1 and BALB/c mice in vitro. Cytopathic changes typical of cytomegalovirus infection, including intranuclear inclusions, developed within the infected cells and eventually resulted in death of infected macrophages. Viral antigens were demonstrable by indirect immunofluorescence microscopy, and morphologically typical herpesvirus particles were observed in both nuclei and cytoplasm of murine cytomegalovirus-infected macrophages. Within 24 h after infection, at which time there was expression of viral antigens but no marcophage death, murine cytomegalovirus-infected macrophages demonstrated marked inhibition of phagocytosis of Staphylococcus aureus. Direct inhibition of macrophage function by cytomegalovirus infection in vivo could impair pulmonary defenses and may account in part for the frequent association of cytomegalovirus infection with other infectious agents. PMID- 6253399 TI - Virus excretion and neutralizing antibody response in saliva in human cytomegalovirus infection. AB - The local secretory immune mechanism in infants with cytomegalovirus infection was studied by a measurement of neutralizing antibody in saliva. Neutralizing antibodies were determined by the microculture plaque assay in 65 saliva specimens including 54 samples from cytomegalovirus-infected subjects and 11 from seronegative controls. In addition, cytomegalovirus isolation from saliva or urine or both and antibody determination in serum and saliva were simultaneously performed on seven infants with cytomegalovirus excretion over long periods. Results obtained were as follows. (i) Neutralizing antibodies were detected in 41 (76%) of 54 saliva specimens obtained from infected subjects but in none of the 11 seronegative controls. (ii) Neutralizing antibodies in saliva were of low titer but persistently detectable in all but one of the seven infants. No relationship was recognized between the cessation of virus excretion and the development of neutralizing antibodies in saliva. (iii) Virus-neutralizing activity was specifically found in the immunoglobulin A fraction of pooled saliva by diethylaminoethyl cellulose chromatography. PMID- 6253398 TI - Persistence of human adenovirus 5 in human cord blood lymphoblastoid cell lines transformed by Epstein-Barr virus. AB - Lymphoblastoid cell lines derived from human cord blood leukocytes were persistently infected with human adenovirus 5. These cell lines expressed the Epstein-Barr nuclear antigen, but no other Epstein-Barr virus-related antigen. They continually produced infectious adenovirus 5 particles, but this production could be inhibited by the presence of specific neutralizing antibody to adenovirus 5. This suggests that the persistent infection might be due to the continual reinfection of susceptible cells by complete virus. PMID- 6253401 TI - Effect of immunosuppression on recurrent herpes simplex in mice. AB - Mice latently infected with herpes simplex virus were treated with immunosuppressive drugs either alone or combined with stimuli to the skin. Treatment with cyclophosphamide reduced spleen weights and severely depressed lymphocyte levels, but had no effect on healing after cellophane tape stripping (CTS) and did not affect the cutaneous hypersensitivity response after injection of inactivated herpes simplex virus. The drug, either used alone or combined with CTS, failed to increase the incidence of recurrent clinical disease, but increased the incidence of virus isolation after CTS. Prednisolone and azathioprine used together also reduced spleen weights and circulating lymphocyte levels. They slightly delayed healing after CTS, but had no effect on cutaneous hypersensitivity to herpes simplex virus. The treatment, either used alone or combined with CTS, slightly increased the incidence of recurrent clinical disease but did not increase the incidence of virus isolation after CTS. Treatment with antithymocyte serum severely depressed the levels of circulating lymphocytes and delayed the regression of HeLa cell tumors in mice. Used alone, the treatment slightly increased the incidence of recurrent clinical disease, but it failed to increase the incidence of recurrences after CTS. It increased the duration of recurrent herpetic lesions, although in uninfected mice healing after CTS was not affected. Silica altered the clinical course of primary infection with herpes simplex virus and increased the incidence of latency in the ganglia. It also delayed healing after CTS in uninfected mice, so it was not tested when recurrent herpes after CTS was assessed clinically. Treatment with silica alone did not increase the incidence of recurrent clinical disease or the incidence of virus isolation after CTS. The results demonstrate that potent immunosuppressive drugs are much less effective than simple cutaneous manipulation in inducing recurrent lesions, and thus argue strongly for the importance of local factors in the pathogenesis of disease. PMID- 6253400 TI - Interaction of streptolysin O from Streptococcus pyogenes and theta-toxin from Clostridium perfringens with human fibroblasts. AB - The membrane-damaging properties on human diploid embryonic lung fibroblasts of streptolysin O (from Streptococcus pyogenes) and theta-toxin (from Clostridium perfringens) were compared. The results are consistent with the suggested mechanism for hemolysis by streptolysin O involving one fixation site and one lytic site of this cytolysin. However, the membrane-damaging activity of the two toxins differed with respect to (i) relative cytolytic activity on human diploid lung fibroblasts compared with that on sheep erythrocytes, (ii) binding to the fibroblast membrane, (iii) activity at 0 degrees C, (iv) membrane repair after more than 30 min, and (v) effect on influx of amino acids. It is concluded that the mechanism of membrane damage caused by theta-toxin differs from that of cytoplasmic membrane. These results question the current concept that all thiol activated, cholesterol-inactivated bacterial toxins are similar both structurally and functionally. PMID- 6253402 TI - Relationship of in vitro immune responses to Epstein-Barr herpesvirus and severity of infectious mononucleosis. AB - Immune responses to Epstein-Barr herpesvirus (EBV) and EBV-related antigens were studied serially in 18 patients with heterophil antibody-positive infectious mononucleosis and in 18 control subjects. Enhanced cellular immune responses to EBV particles and to EBV intracellular soluble antigens were found in the patients at convalescence, suggesting that the development of specific cellular immune responses was associated with apparent control of the virus infection. In addition, a correlation between severity of disease and specific cellular immune response was found. Patients with severe clinical signs were found to have a more active cellular immune response to EBV intracellular soluble antigens early in the infection compared with patients with mild disease. This suggests that an increased immune reactivity to intracellular antigens during the early part of the illness is related to the severity of clinical manifestations in infectious mononucleosis. Serum antibody to viral capsid antigen and early antigen was not related to the severity of clinical disease. PMID- 6253403 TI - Variations in the contribution of induced interferon and adjuvanticity to the antiviral effect of different polyinosinic acid . polycytidylic acid formulations in mice infected with encephalomyocarditis virus. AB - Treatment of mice with polyinosinic acid . polycytidylic acid [poly(I) . poly(C)] 6 h before infection and once daily on days 1, 2, 3, 4, 7, and 10 after infection with encephalomyocarditis virus was found to confer no additional protection as compared with a single treatment 6 h before infection. When complexed with a colloid formed between carboxymethylcellulose and polylysine, poly(I) . poly(C) conferred significant additional protection with the multiple treatment regimen compared with a single treatment of 6 h before infection. The additional antiviral activity of multiple treatments could not be entirely attributed to interferon induction by the complexed form of poly(I) . poly(C), because free and complexed poly(I) . poly(C) both caused hyporesponsiveness to interferon induction after multiple treatments. However, mice protected against encephalomyocarditis virus infection by multiple treatments with the colloidal complex form of poly(I) . poly(C) showed a significant increase in resistance to reinfection, and this was attributable to adjuvant effects of the colloidal complex form of poly(I) . poly(C). The contribution of interferon induction and adjuvanticity of the poly(I) . poly(C) formulations varied with the times of treatment relative to infection, the dose of polynucleotide material, and the virus dose. PMID- 6253404 TI - Detection and quantification of type C viral proteins in tissues and sera with an enzyme immunoassay. AB - The detection and quantification of retroviral proteins in cells, tumors, and sera by an enzyme immunoassay technique (enzyme-linked immunosorbent assay [ELISA]) is described. The ELISA technique has been applied to three viral systems: murine leukemia virus, baboon endogenous virus, and simian sarcoma virus. By detecting 0.1 nf of retroviral antigen, the sensitivity of the ELISA is comparable to that of the competition radioimmunoassay technique. PMID- 6253406 TI - Herpes zoster in a husband and wife. AB - The wife of a 75-year-old man with zoster began to suffer from this disease some 24 days after is appeared in her husband. Although zoster is generally regarded to be an endogenously noncommunicable disease, the case reported herein suggests that the infection was exogenously communicated. The literature pointing up that zoster may possibly be acquired exogenously, particularly in immunosuppressed patients, is extensively reviewed. PMID- 6253405 TI - Peripheral nervous system functions of workers exposed to n-hexane at a low level. AB - In order to assess the effects on the peripheral nervous system of n-hexane at a low level, an epidemiological study using a questionnaire, neurological examinations, and neurophysiological studies was carried out on two age-matched groups; one, consisting of 14 exposed workers and the other, of 14 control workers. The 8 h time weighted average of n-hexane concentration in the exposure environment was 58 +/- 41 (mean +/- SD) ppm. In the individual worker, no obvious signs could be found indicating damage to the nervous system that were referable to the n-hexane exposure. On the other hand, when the subjects were taken in groups, the results obtained from the exposed group showed a minor partiality for functional impairment of the peripheral nervous system in many test items. In particular, statistically significant differences between the two groups were detected in the following items: (1) inquiries by questionnaire for persistent or transient symptoms regarding muscle weaknesses and dyesthesia of limbs; (2) the jump test on one foot; (3) the tuning fork test for vibration sensation on the radial processes; (4) the maximal velocity and the residual latency of motor nerve conduction of the posterior tibial nerve. In conclusion, it is not likely that at exposure levels less than the current threshold limit value of 100 ppm proposed by ACGIH, n-hexane may induce clinically overt polyneurophathy. However, there is no gainsaying the possibility that in the exposed workers as a whole, small cumulative effects in the peripheral nervous system may be brought about by long-term n-hexane exposure less than 100 ppm. PMID- 6253407 TI - The activity of superoxide dismutase in the liver and bone marrow of gamma irradiated rats. PMID- 6253408 TI - An e.s.r. study of stable radicals in gamma-irradiated single crystals of uridine 5'-phosphate (Na salt). AB - Electron spin resonance has been used for the study of the radical in gamma irradiated single crystals of 5'-UMP (sodium salt). Six types of radicals have been identified at room temperature. They are formed by addition of H atoms to C5, C6, 02 and 04, and by an OH addition to C5 of the uracil ring. Five of these radicals have an appreciable spin density on C6. The radicals with the addition to C5 or C6 are less stable than than the essentially planar radicals with the H addition to 02 and 04. PMID- 6253409 TI - DNA repair of U.V.-damage in heterochromatin and euchromatin of rat liver. PMID- 6253410 TI - Cholera toxin stimulates adenosine 3',5'-monophosphate synthesis and epithelial wound closure in the rabbit cornea. AB - Rabbit corneas were treated in vitro and in vivo with cholera toxin (CTX), a specific and irreversible activator of adenylate cyclase. Tissue pieces incubated in vitro in the presence of 10 mug/ml CTX for 15 min continuously synthesized adenosine 3',5'-monophosphate (cyclic AMP) at an increased rate for 3 hr in the absence of CTX in the medium. Corneas exposed for 10 min to CTX topically in vivo and after various time intervals incubated in vitro had an increased ability to synthesize cyclic AMP for at least 30 hr after topical treatment. Epithelial wounds, 6 mm in diameter, were made by brief exposure of corneas in vivo to filter disks soaked in heptanol. Wounds in corneas pretreated with CTX closed at a faster rate and earlier than wounds in corneas pretreated with inactivated CTX. We postulate that cyclic AMP mediates the initial events governing the rate of closure of an epithelial defect. PMID- 6253411 TI - Topical vanadate lowers intraocular pressure in rabbits. AB - In unanesthetized rabbits the topical application of vanadate lowered intraocular pressure. Tonographic outflow facility and episcleral venous pressure were unaltered by topical vanadate. As estimated from the tonographic data, aqueous humor flow was reduced by approximately 30%. Posterior chamber aqueous humor ascorbate increased in the eye receiving topical vanadate, and this was compatible with a decreased rate of aqueous humor flow. Topical vanadate did not alter anterior chamber aqueous humor protein or cyclic AMP. In five monkeys intraocular pressure was also significantly reduced by topical vanadate. PMID- 6253412 TI - Adrenergic alpha receptors outnumber beta receptors in human penile corpus cavernosum. AB - Using specific adrenergic receptor binding assays, we characterized both alpha and beta adrenergic receptors in human penile corpus cavernosum tissue. The density of alpha adrenergic receptors in corporal tissue was found to be almost ten times greater than the density of beta adrenergic receptors. Our results are compatible with studies that suggest an important role for adrenergic innervation in penile erection. PMID- 6253413 TI - Wilms' tumour and associated congenital anomalies. PMID- 6253414 TI - Pivmecillinam in the treatment of recurrent urinary infection in girls. PMID- 6253415 TI - Reconstruction of the floor of the mouth by an arteriolized dorsalis pedis free flap. AB - A new one-stage technique of reconstruction of the floor of the mouth, in which a free dorsalis pedis artery flap is used, was performed in five cases. The indications, implications and possibilities of this technique are discussed. PMID- 6253416 TI - [Genetically determinded deafness; 5 cases of Pendred's syndrome (author's transl)]. AB - In our experience, Pendred's Syndrome is the most frequent one clinically seen of 124 syndromes with genetically determined deafness. It is defined as a triad: congenital perceptive hearing loss, goiter, and an abnormal perchlorate test. Inheritance is by an autosomal-recessive pattern. In 5 patients seen by us--one of whom had experienced multiple episodes of sudden deafness--the difficulty of diagnosis is shown. We also emphasize the need for genetic counselling in families with the known syndrome. PMID- 6253417 TI - Gray scale ultrasonographic appearance in hepatocellular carcinoma. PMID- 6253418 TI - The development and implementation of nursing audit in a community health agency. PMID- 6253420 TI - Anxiety in the undergraduate medical-surgical clinical student. PMID- 6253419 TI - Exploration of the effect of educational level on the nurse's attitude toward discharge teaching. PMID- 6253421 TI - Clinical objectives for nurse practitioner students. PMID- 6253423 TI - A model for career development. PMID- 6253422 TI - Health education: are nurses really prepared? PMID- 6253424 TI - Selection of clinical agencies for baccalaureate nursing education. PMID- 6253425 TI - Spontaneous shedding of pseudorabies virus from a clinically recovered postparturient sow. AB - Pseudorabies virus was shed by a sow that had been clinically infected 19 months earlier (when 1 month old) and had been in isolation for 3 1/2 months. The shedding was detected from the third to eighth days after farrowing and was confined to the nasal secretion. Two susceptible pigs in contact with the sow after farrowing were not infected. PMID- 6253426 TI - Nitrate intoxication. PMID- 6253427 TI - Induced synthesis of phosphatases in Anacystis nidulans by p-NO2-phenylserinal. PMID- 6253428 TI - Utilization of Cibacron Blue 3G-A Sepharose 6B in the isolation and enrichment of pyruvate, phosphate dikinase, alanine dehydrogenase, and phosphoenolpyruvate carboxylase from mitomycin-producing Streptomyces verticillatus. PMID- 6253429 TI - Antibacterial activity of a new cephalosporin, cefotaxime. PMID- 6253430 TI - Induction of accelerated sporangial lysis by basic peptide antibiotics. A novel method of preparation of free spores of bacilli. PMID- 6253431 TI - Relationship between the increased sensitivity of heat injured Clostridium perfringens spores to surface active antibiotics and to sodium chloride and sodium nitrite. PMID- 6253432 TI - Synergy between cefotaxime, cefsulodin, azlocillin, mezlocillin and aminoglycosides against carbenicillin resistant or sensitive Pseudomonas aeruginosa. PMID- 6253433 TI - The in vitro antibacterial activity of cefotaxime compared with that of cefuroxime and cefoxitin. PMID- 6253435 TI - Mecillinam and enteric fever. PMID- 6253434 TI - The influence of gastric acidity on the bio-availability of ketoconazole. PMID- 6253436 TI - Excretory urography in infants: recent aspects in contrast medium risk. PMID- 6253437 TI - Instability in tyrR strains of plasmids carrying the tyrosine operon: isolation and characterization of plasmid derivatives with insertions or deletions. AB - The transformation of tyrR strains of Escherichia coli with multicopy plasmids which carry the tyrosine operon gave rise to modified plasmids with either insertions or deletions. The effect of each of these insertions or deletions was to decrease the level of expression of this operon. It is proposed that plasmid instability arose as a direct consequence of the metabolic effects of an overproduction of the enzymes coded for by the tyrosine operon. The results have significant implications for the cloning of genes that are repressed by the product of a regulatory gene. Since the predominant plasmid modification observed was the insertion of an IS1 element near the regulatory region of the tyrosine operon, the results also suggest a role for IS1 elements in the regulation of gene expression. PMID- 6253438 TI - Conservation and variation of nucleotide sequences in Escherichia coli strains isolated from nature. AB - A group of Escherichia coli isolates from nature were compared with one another and with laboratory strains of E. coli with respect to size distribution of chromosomal restriction endonuclease fragments and differences in nucleotide sequences in selected small portions of the genomes. The estimated frequency of base substitutions in nucleotide sequences in and near the trp operons of 26 of the 28 E. coli strains examined ranged from 0.008 to 0.066. Nucleotide sequences in or near lambda prophage homologs were significantly more variable than the sequences in or near trp, tnaA, and thyA genes. Thus, the lambda-homologous regions may have a significant horizontal component in their evolutionary histories, having undergone genetic exchange, whereas the trp, tnaA, and thyA regions may have solely vertical evolutionary histories. The relatedness of the E. coli strains in the genetic regions studied indicated that laboratory strains are not more closely related to one other than they are to isolates from nature. The isolates from natural populations did not form groups related either by host taxa or by geographical region of isolation. PMID- 6253439 TI - Capnocytophaga spp. contain sulfonolipids that are novel in procaryotes. AB - A group of unusual sulfonolipids was found in bacteria of the genus Capnocytophaga. One of these lipids, to which we have assigned the trivial name capnine, was isolated in 98% pure form and was identified, by infrared absorption spectrometry, high-resolution mass spectrometry, and other methods, as 2-amino-3 hydroxy-15-methylhexadecane-1-sulfonic acid. Another lipid appears to be an N acylated version of capnine; after acid hydrolysis, its sulfur was recovered in a form chromatographically indistinguishable from that of capnine. The new lipids are related structurally to sphingosine and the ceramides, respectively, but differ markedly from those compounds in important respects, notably the presence of the sulfonate group. Some Capnocytophaga strains accumulated mostly capnine, whereas others accumulated mostly N-acylcapnine. All seven strains examined were found to contain the new lipids, in amounts ranging from 7 to 16 mumol/g of cells (wet weight). The lipids were found in isolated cell envelopes, where they were present in amounts ranging up to 400 mg/g of envelope protein; they are, accordingly, major cell components. PMID- 6253440 TI - Genetic transformation of Streptococcus pneumoniae by heterologous plasmid deoxyribonucleic acid. AB - A number of heterologous plasmid deoxyribonucleic acids (DNAs) coding for erythromycin, tylosin, lincomycin, tetracycline, or chloramphenicol resistance have been introduced into Streptococcus pneumoniae via genetic transformation with frequencies that varied between 10(-5) to as high as 5 x 10(-1) per colony forming unit. Transformation with plasmid DNA required pneumococcal competence, was competed by chromosomal DNA, and showed a saturation at about 0.5 micrograms/ml (with a recipient population of 3 x 10(7) colony-forming units of competent cells per ml). Plasmid transformation did not occur with a recipient strain, 410, defective in endonuclease I activity and in chromosomal genetic transformation. All erythromycin-resistant transformants examined contained covalently closed circular DNA with the same electrophoretic mobility on agarose gels as the donor DNAs, and when examined in detail the plasmid reisolated from the transformants had the same restriction patterns and the same specific transforming activity as the donor DNA. In the cases of two plasmids examined in detail--pAM77 and pSA5700 Lc9--most of the transforming activity was associated with DNA monomers; DNA multimers present in pSA5700 Lc9 also had biological activity. An unexpected finding was the demonstration of transformation (2 x 10( 5) per colony-forming unit) with plasmid DNAs linearized by treatment with S1 nuclease or with restriction endonucleases. PMID- 6253441 TI - Agrobacterium tumefaciens mutants affected in crown gall tumorigenesis and octopine catabolism. AB - Mutants of Agrobacterium tumefaciens which affect virulence or the ability to catabolize octopine were isolated after Tn5-induced mutagenesis. Of 8,900 colonies tested, 7 mutants with Tn5 insertions in a specific region of other Ti plasmid unable to catabolize octopine were isolated. Thirty-seven mutants affected in tumorigenesis resulted from insertions in the Ti plasmid and the Agrobacterium chromosome. Of these mutations, 12 were chromosomal and 25 mapped on the plasmid. Twenty-three mapped within a 20-megadalton region, which is distinct from the Ti plasmid sequences found stably integrated into the plant cell genome T-deoxyribonucleic acid). Included in these were mutants that were either a virulent or produced tumors with unusual morphologies. Three mutants contained insertions in the T-deoxyribonucleic acid. These three mutants incited tumors which synthesized octopine but had an altered morphology due to either extensive proliferation of shoots or roots from the tumor callus. Three additional mutants not caused by Tn5 contained mutations in the Ti plasmid. PMID- 6253442 TI - Chemiluminescence by Listeria monocytogenes. AB - Listeria monocytogenes cells suspended in brain heart infusion broth or in carbonated saline solution emitted light (chemiluminescence) that could be detected by a liquid scintillation spectrometer. This chemiluminescence was inhibited by superoxide dismutase and catalase but not by the hydroxyl radical scavengers mannitol and benzoate; it was also dependent upon and proportional to the carbonate ion concentration in the medium. Organisms suspended in carbonated saline solution which had ceased to chemiluminesce immediately began to chemiluminesce again when acetaldehyde was added but not when glucose, sucrose, or xanthine was added. Acetaldehyde-induced chemiluminescence was inhibited by suproxide dismutase and catalase but not by allopurinol. Our data indicate that the superoxide anion, hydrogen peroxide, and the carbonate ion are involved in chemiluminescence by L. monocytogenes. Chemiluminescence is apparently initiated by the extracellular generation of superoxide anon by this organism. The mechanism for the production of the superoxide anion is not known, but xanthine oxidase does not appear to be involved. PMID- 6253443 TI - Molecular cloning of an erythromycin resistance determinant in streptococci. AB - The erythromycin resistance determinant of plasmid pDB102, a derivative of plasmid pSM19035, was cloned into the single HindIII site of the 3.6-megadalton cryptic Streptococcus mutans plasmid pVA318 and introduced into Streptococcus sanguis strain Challis by transformation. Plasmid pDB201, which was isolated from one of the transformants, consisted of the vector plasmid and the 1.15-megadalton HindIII fragment D of pSM19035. HindIII fragment D contained within it one of the two unique "spacer" sequences of pSM19035. Electron micrographs of self-annealed molecules of the recombinant plasmid revealed classical stem-loop structures, and the resistance determinant of pSM19035 appeared as a transposon-like structure. No differences were observed in either the type or the level of erythromycin resistance by pSM19035 or pDB201. The availability of a cloned erythromycin resistance determinant should be useful for future comparative studies of macrolide, lincosamide, and streptogramin B resistance plasmids in streptococci. PMID- 6253444 TI - Bacteriophage P1 as a vehicle for Mu mutagenesis of Salmonella typhimurium. AB - We developed a procedure using bacteriophage P1 as a vector for transferring Mu phage deoxyribonucleic acid into Salmonella typhimurium. Mu phage transferred in this manner yielded lysogenic auxotrophs, and we demonstrated that specific deletions and lac gene fusions can be selected. PMID- 6253445 TI - 1,25-dihydroxyvitamin D3 receptors. Differential quantitation of endogenously occupied and unoccupied sites. PMID- 6253446 TI - Deoxyuridine triphosphate pools after polyoma virus infection. AB - The synthesis of polyoma DNA in virus-infected 3T6 mouse fibroblasts is discontinuous with the intermediate formation of short Okazaki fragments. Hydroxyurea, an inhibitor of the enzyme ribonucleotide reductase, inhibits polyoma DNA synthesis, as measured by incorporation of radioactive thymidine. In the inhibited state, almost all incorporation occurs into short fragments. We investigated to what extent formation of short DNA fragments might be the result of incorporation of deoxyuridine triphosphate (dUTP) into DNA, followed by excision and repair reactions. We devised a sensitive enzymatic method for measuring dUTP in cell extracts which allows the determination of the dUTP pool when this pool amounts to between 0.1 and 2% of the dTTP pool. No dUTP was detected in growing mouse fibroblasts. After infection with polyoma virus cell extracts contained 0.4% dUTP (of dTTP) at the peak of DNA synthesis. Addition of hydroxyurea at this point led to a disappearance of dUTP. We conclude that dUTP incorporation can contribute only minimally to the generation of short fragments during polyoma DNA synthesis. PMID- 6253447 TI - Slow interaction of islet-activating protein with pancreatic islets during primary culture to cause reversal of alpha-adrenergic inhibition of insulin secretion. AB - The manner in which islet-activating protein (IAP), a protein purified from the culture medium of Bordetella pertussis, interacts with the islet B-cell was studied by following the progressive development of IAP-induced reversal of alpha adrenergic inhibition of insulin release during maintenance of islets in culture with glucose and epinephrine. This action of IAP developed in an exponential manner dependent on its concentration after a true lag period of about 1 h. The lag period was not grossly dependent on the concentration of IAP added but highly dependent on temperature of culture, and was still seen upon adding a second dose of IAP to partially stimulated cells. After 24-h culture significantly more insulin was secreted with IAP at a concentration as low as 1 pg/ml and the half maximal effect was observed at 0.1 ng/ml. The development of IAP action occurred even in the islets that had been exposed to IAP for only 30 s, but was significantly prevented by anti-IAP serum added before the end of the lag period. IAP was effective in the presence of cycloheximide, an inhibitor of protein synthesis, or of vinblastine or cytochalasin B, microtubular-microfilamentous modifiers. It is suggested that the IAP molecule is rapidly bound to the receptor area of the islet B-cell and then is gradually inserted into the cell membrane before appearance of its action to activate native calcium ionophores. This slow interaction of IAP with the membrane may be responsible for potentiation of insulin secretory and cAMP responses of the cell to various stimuli as well as for reversal of alpha-adrenergic inhibition. PMID- 6253448 TI - Phosphomannosyl-enzyme receptors in rat liver. Subcellular distribution and role in intracellular transport of lysosomal enzymes. AB - beta-Hexosaminidase B purified from human fibroblast secretions was used as a ligand to study phosphomannosyl-enzyme receptors in membranes from rat tissues. Enzyme binding to rat liver membranes was saturable, competitively inhibited by mannose 6-phosphate, not dependent on calcium, and destroyed by prior treatment of the hexosaminidase with either alkaline phosphatase or endoglycosidase H. Most (90%) of the phosphomannosyl-enzyme receptors were found in endoplasmic reticulum, Golgi apparatus, and lysosomes; 9.5% in the plasma membrane, and less than 1% in nuclei and mitochondria. Receptors were vesicle-enclosed in all fractions except plasma membrane. Receptors in the endoplasmic reticulum apparently were occupied by endogenous ligands, but most receptors in lysosomes and plasma membrane were unoccupied. Most of the endogenous beta-hexosaminidase was in lysosomes and was released from vesicles by detergent treatment. Displacement of the residual receptor-bound endogenous beta-hexosaminidase (mostly in endoplasmic reticulum and Golgi apparatus) from detergent-treated membranes by mannose 6-phosphate released high uptake enzyme with properties expected for phosphomannosyl-enzymes. Mannose 6-phosphate-inhibitable enzyme receptor activity was found in nine rat organs and correlated roughly with their lysosomal enzyme content. These data support a general model for lysosomal enzyme transport in which the phosphomannosyl-enzyme receptor acts as a vehicle for delivery of newly synthesized acid hydrolases from the endoplasmic reticulum to lysosomes. PMID- 6253449 TI - Hemoglobin-haptoglobin receptor in rat liver plasma membrane. AB - The presence of a receptor specific for the hemoglobin . haptoglobin complex is demonstrated in rat liver plasma membranes. Hemoglobin . haptoglobin complex, administered intravenously to rats, was cleared from the circulation at a constant rate with exclusive incorporation of the molecule into hepatocytes. This incorporation was unaffected by the simultaneous injection of asialoglycoprotein or heme . hemopexin complex. In vitro experiments with isolated liver plasma membranes indicated the absence of competitive binding of these molecules to the membrane and suggested that this receptor might recognize an altered conformation of the haptoglobin moiety of the complex resulting from the binding with hemoglobin. These observations suggest that the mechanism of recognition and binding of hemoglobin . haptoglobin complex by the receptor is different from that of the asialoglycoprotein receptor or heme . hemopexin receptor. PMID- 6253450 TI - Interactions of cytochrome c with mitochondrial membranes. Binding to succinate cytochrome c reductase. AB - Methyl-4-azidobenzoimidate was reacted with horse heart cytochrome c to give a photoaffinity-labeled derivative of this heme protein. The modified cytochrome c bound to cytochrome c-depleted mitochondria with the same Kd as native cytochrome c and restored oxygen uptake to the same extent. Irradiation of cytochrome c depleted mitochondrial membranes with 3- to 4-fold excess of photoaffinity labeled cytochrome c over cytochrome c oxidase resulted in covalent binding of the derivative to the membranes. Fractionation of the irradiated mitochondria in the presence of detergents and salts followed by chromatography on an agarose Bio Gel-A-5m showed that the labeled cytochrome c was bound covalently to succinate cytochrome c reductase. The covalently bound cytochrome c was active in mediating electron transfer between its reductase and oxidase. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of the succinate-cytochrome c reductase containing photoaffinity-labeled 125I-cytochrome c showed that the reductase contained a protein binding site for cytochrome c. It is suggested that cytochrome c1 is the most likely site for the cytochrome c binding in mitochondria in situ. PMID- 6253451 TI - Oligothymidylate analogues having stereoregular, alternating methylphosphonate/phosphodiester backbones. Synthesis and physical studies. AB - Two decathymidylate analogues, d-(TpTp)4TpT-isomer 1 and isomer 2, having stereoregular, alternating methylphosphonate/phosphodiester backbones were prepared. The phosphodiester linkages of d-(TpTp)4TpT are cleaved slowly by snake venom phosphodiesterase in a stepwise manner, while slow random cleavage occurs with micrococcal nuclease which hydrolyzes isomer 2 faster than isomer 1. The CD spectra of isomer 1 and d-(Tp)9T are identical suggesting they have similar conformations, while that of isomer 2 shows an overall reduction of [theta]. Isomer 1 forms a 1T . 1A complex with poly(dA) and both 1T . 1A and 2T . 1A complexes with poly(rA), while isomer 2 forms a 2T . 1A complex of low thermal stability with poly(dA) and no complex with poly(rA). The Tm values of the partially nonionic d-(TpTp)4TpT . polynucleotide complexes are less dependent on salt concentration than are those of d-(Tp)9T. The stoichiometry and CD spectra of the complexes suggest that poly(dA) . isomer 1 duplex assumes a B-type geometry while isomer 2 . poly(dA) . isomer 2 triplex and the isomer 1 . poly(rA) complexes have an A-type geometry. Although there are no apparent differences between steric restrictions to rotation about the backbones of either isomer 1 or 2, or steric restrictions to complex formation, the results suggest that the configuration of the methylphosphate linkage controls: 1) interaction with nucleases, 2) oligomer conformation, and 3) interaction with polynucleotides. The latter effects may result from differences in solvation of the two isomers. PMID- 6253452 TI - Kinetics of the reduction of horse heart ferricytochrome c. Ascorbate reduction in the presence and absence of urea. AB - The reduction of horse heart cytochrome c with ascorbate in the absence of urea and in its presence, 0 to 8 M, pH 7.0, has been investigated using a stopped flow technique and the absorptivity at 550 nm as the monitoring probes, and by using the rate of oxidizability with molecular oxygen. Reduction is found to be consistent with a mechanism involving (i) a urea-dependent equilibrium step between an ascorbate-reducible and an irreducible form, with a [urea]1/2 of 7.5 M and a reversion rate constant of 0.05 +/- 0.02 s-1, (ii) the binding of ascorbate to cytochrome c, with a binding constant of 5.9 M-1 in the absence of urea which decreases to a value of 2.7 M-1 above 5.5 M urea, and (iii) a reduction step, with a urea-independent rate constant of 2.9 +/- 0.3 s-1. This scheme is interpreted in terms of an electron-transfer pathway involving neither the classical "adjacent" attack nor attack at the exposed heme edge, i.e. "remote" attack, but rather, through an alternate pathway involving binding at some site other than the heme crevice opening and a migration path of rather low electron transfer efficiency. The urea-linked ascorbate reduction step is th X2 in equilibrium D step of the urea denaturation mechanism (Myer, Y. P., MacDonald L. H., Verma, B. C., and Pande, A. J. (1980) Biochemistry 19, 199-207), and the 9 M urea form, D, is the irreducible form. Form X2 and the other intermediate form, X1, are found to be reducible directly by ascorbate, and not through reversion to the native form of the protein. both the integrity of the heme crevice and the polypeptide-organized structures are of little importance as far as ascorbate reducibility is concerned, but the integrity of the structural and protein functional changes reflecting the X2 in equilibrium D step of the mechanism directly or indirectly determines the reducibility of the protein. PMID- 6253453 TI - Assembly of the mitochondrial membrane system. Complete restriction map of the cytochrome b region of mitochondrial DNA in Saccharomyces cerevisiae D273-10B. AB - The cytoplasmic petite (rho-) mutant DS400/A12 has been obtained from the wild type strain of Saccharomyces cerevisiae D273-10B/A21. The DS400/A12 clone has a mitochondrial genome with a 7.6-kilobase pair, tandemly repeated segment of DNA. Genetic tests indicate that DS400/A12 contains all the cob1 and cob2 markers of the cytochrome b gene. The gene has been further dissected by mutagenesis of DS400/A12 and selection of secondary rho- clones with simpler genotypes. Restriction analysis of the mtDNAs of the rho- clones was used to construct the complete restriction map of the cytochrome b region and to map the mutations within narrowly defined physical limits. The cytochrome b mutants scatter over a maximal distance of 3.3 kilobase pairs. All the mutations assigned previously to the cob2 locus are found between 71.6 and 73.2 units. The cob1 mutations are located between 74.6 and 76.3 units. The estimated distance between the two loci is at least 1 kilobase pair. PMID- 6253454 TI - Assembly of the mitochondrial membrane system. DNA sequence and organization of the cytochrome b gene in Saccharomyces cerevisiae D273-10B. AB - The mitochondrial genomes of cytoplasmic "petite" (rho-) mutants of Saccharomyces cerevisiae have been used to sequence the cytochrome b gene. A continuous sequence of 6.2 kilobase pairs has been obtained from 71.4 to 80.2 units of the wild type map. This region contains all the cytochrome b mutations previously assigned to the cob1 and cob2 genetic loci. Analysis of the DNA sequence has revealed that in the strain D273-10B, the cytochrome b gene is composed of three exons. The longest exon (b1) codes for the first 252 to 253 amino acids from the NH2-terminal end of the protein. The next two exons (b2 and b3) code for 16 to 18 and 115 to 116 amino acids, respectively. The complete cytochrome b polypeptide chain consists of 385 amino acids. Based on the amino acid composition, the yeast protein has a molecular weight of 44,000. The three exon regions of the cytochrome b gene are separated by two introns. The intron between b1 and b2 is 1414 nucleotides long and contains a reading frame that is continuous with the reading frame of exon b1. This intron sequence is potentially capable of coding for another protein of 384 amino acid residues. The second intron is 733 nucleotides long. This sequence is rich in A + T and includes a G + C cluster that may be involved in processing of the cytochrome b messenger. The organization of the cytochrome b region in S. cerevisiae D273-10B is somewhat less complex than has been reported for other yeast strains i which exon b1 appears to be further fragmented into three smaller exons. PMID- 6253455 TI - A study of the vanadate-trapped state of the (Na,K)-ATPase. Evidence against interacting nucleotide site models. AB - The state of the Na+- and K+-stimulated adenosine triphosphatase ((Na,K)-ATPase) which binds vanadate was investigated by taking advantage of the slow rate of vanadate release (koff = 0.32/h at 25 degrees C and 0.045/h at 4 degrees C). Vanadate release from the enzyme could be accelerated approximately 2-fold by addition of K+ and 50-fold by addition of Na+. The K+ effect saturated hyperbolically with a K1/2 of 0.5 mM, while the Na+ effect had a sigmoidal activation curve and K1/2 of 250 mM. These results indicate that either Na+ or K+ can equilibrate with the vanadate-"trapped" enzyme prior to vanadate release. In the presence of vanadate, a saturable Mn2+ binding site could be detected with a dissociation constant of 120 nM. When 54Mn2+ was added during incubation of the enzyme with vanadate, 1 mol of 54Mn2+ could be trapped/mol of vanadate trapped and the two metals dissociated in parallel. This result indicates a single divalent cation site is involved in stabilizing vanadate (and probably phosphate) binding. Addition of 1 to 4 mM of ATP to the vanadate-trapped enzyme had no affect on the rate of vanadate release. Also, the high affinity ATP site could not be detected in equilibrium-binding studies with the vanadate-trapped enzyme. Since kinetic experiments indicate that vanadate binding is competitive with the low affinity ATP site (Cantley, L. C., Jr., Cantley, L. G., and Josephson, L. (1978) J. Biol. Chem. 253, 7361--7368) and the high affinity ATP site is absent on vanadate-trapped enzyme, it appears unlikely that ATP can occupy either a high or low affinity site on the vanadate-trapped enzyme. We show that nonlinear Lineweaver-Burk plots for ATP hydrolysis can be explained by a single hydrolysis site which exhibits a low affinity for ATP prior to the rate-limiting E2 to E1 conformational change, but a high affinity for ATP following the conformational change. PMID- 6253456 TI - Rat alveolar macrophages require NADPH for superoxide production in the respiratory burst. Effect of NADPH depletion by paraquat. AB - Alveolar macrophages can be stimulated by concanavalin A to produce extracellular superoxide. Conflicting opinions exist, however, concerning the relative importance of the oxidation of either NADPH or NADH in the generation of (Formula: see text) by surface membrane-stimulated phagocytic cells. Alveolar macrophages were obtained from adult male rats by lavage with phosphate-buffered saline. Cells (approximately 10(6)/ml) were incubated in Krebs-Ringer phosphate 4 (2-hydroxyethyl)-1-piperazineethanesulfonic acid buffer and ferricytochrome c for 15 min at 37 degrees C before addition of concanavalin A. Release of (Formula: see text) was detected as the difference in cytochrome c reduction, followed at 550 nm, in the absence and presence of superoxide dismutase. Superoxide production by concanavalin A-stimulated alveolar macrophages was markedly increased in the presence of glucose but fructose, lactate, and pyruvate were without effect. Paraquat (methylviologen), an oxidation-reduction dye, significantly reduced concanavalin A-stimulated (Formula: see text) production when incubated at 1 mM with alveolar macrophages in the absence of glucose. The effect of paraquat was reversed by glucose, but fructose, lactate, and pyruvate could not reverse paraquat inhibition. Paraquat enhanced oxidation of NADPH (but not NADH) by cell supernatant and increased pentose phosphate shunt activity in resting macrophages, but did not affect mitochondrial respiration or ATP content of alveolar macrophages. These results suggest that paraquat is able to specifically deplete NADPH in alveolar macrophages while not affecting NADH or ATP. Our conclusion is that NADPH is essential for the production of (Formula: see text) by concanavalin A-stimulated alveolar macrophages. PMID- 6253457 TI - Stacking interactions in fluorescent nucleotide analogs containing 1 aminonaphthalene-5-sulfonate at the phosphoryl terminus. AB - The conformational properties of nucleotides containing the fluorophore 1 aminonaphthalene-5-sulfonate attached via a gamma-phosphoamidate bond have been examined. Measurements of fluorescence excitation spectra show that energy absorbed by adenine in the ATP analog is transferred to the naphthalene moiety with an efficiency of approximately 43%. In nonpolar solvents transfer is almost eliminated. The fluorescence intensity of the UTP analog is quenched. Measurements of quantum yield and excited state lifetime show that this occurs by both dynamic and static mechanisms. Thus, fluorescence studies show that both the purine and pyrimidine analogs exist in an equilibrium mixture of stacked and unstacked forms. NMR studies show that the base and ribose protons of the ATP and UTP analogs are shifted upfield by about 0.2 to 0.3 ppm, presumably due to ring current effects produced by stacking interactions. Phosphorus NMR spectra of the ATP analog are generally similar to spectra of unmodified ATP. The strong dependence on conformation of the fluorescence of the pyrimidine analogs may prove useful in studies of protein-nucleotide interactions. PMID- 6253458 TI - The role of superoxide in the destruction of erythrocyte targets by human neutrophils. AB - Human neutrophils exposed to the soluble stimulus, phorbol myristate acetate, generate a flux of O2.- which can destroy human erythrocyte targets. Under optimal conditions, each neutrophil was capable of lysing almost 10 erythrocyte targets. Hemolysis was inhibited by exogenous copper-zinc or iron superoxide dismutase while neither heat-denatured enzyme nor albumin inhibited cytotoxicity. Although neutrophils can also generate H2O2, neither catalase nor a glutathione glutathione peroxidase system inhibited hemolysis. Hemolysis was prevented by conversion of the hemoglobin to carbon monoxyhemoglobin, suggesting an intracellular mechanism of cytotoxicity. Conversion of hemoglobin to methemoglobin by nitrite treatment did not impair neutrophil-mediated hemolysis. However, nitrite-treated targets were not protected by superoxide dismutase, while exogenous catalase inhibited cytotoxicity, suggesting a potential role for H2O2 and methemoglobin. H2O2 and methemoglobin are known to interact to form an oxidant complex whose cytotoxic potential was underlined by the marked sensitivity of nitrite-treated cells to commercial H2O2. It is proposed that neutrophil-derived O2.- oxidizes oxyhemoglobin to generate methemoglobin and H2O2 which interact to form a cytotoxic complex capable of hemolyzing the erythrocyte target. PMID- 6253459 TI - Affinity labeling of the digitalis receptor with p-nitrophenyltriazene-ouabain, a highly specific alkylating agent. AB - Three derivatives of ouabain have been synthesized which alkylate the digitalis receptor. These derivatives were formed through reductive amination of p nitrophenyltriazene (NPT) ethylenediamine to the periodate-oxidized rhamnose moiety of ouabain. The non-covalent binding of the ouabain derivatives (NPT ouabain, designated I, II, and III) was followed (i) by their ability to inhibit the activity of sodium- and potassium-activated ATPase ((Na+,K+)-ATPase) purified from the electric organ of Electrophorus electricus, (ii) by the binding of [3H]NPT-ouabain I to the enzyme, and (iii) by the inhibition of [3H]ouabain binding with unlabeled NPT-ouabain I. Covalent modification of the digitalis site of (Na+,K+)-ATPase occurs after long periods of time. At pH 7.5 (25 degrees C) the best alkylating derivative, NPT-ouabain I, gives maximum covalent labeling after 6 h. Only the large polypeptide chain (Mr = 93,000) of the purified enzyme is specifically labeled with [3H]NPT-ouabain I while the glycoprotein chain (Mr = 47,000) is not significantly labeled. Labeling of a microsomal fraction of the electric organ with [3H]NPT-ouabain I gave the same type of gel pattern as that observed with the purified enzyme. [3H]NPT-ouabain I was also used to label the digitalis receptor in highly purified axonal membranes and in cardiac membranes prepared from embryonic chick heart. Although the (Na+,K+)-ATPase in both types of membranes has a low affinity for ouabain, [3H]NPT-ouabain I proved to be a very efficient affinity label for the digitalis receptor. In the complex mixture of polypeptides found in these membrane preparations, only a single polypeptide chain having a Mr = 93,000 is specifically labeled by [3H]NPT-ouabain I. PMID- 6253460 TI - The localization of tightly bound cardiolipin in cytochrome oxidase. AB - One to two molecules of tightly bound cardiolipin are associated with resolved fractions of cytochrome oxidase containing subunits I to III or I to IV. Large scale isolation of subunits I to IV indicates the presence of approximately 0.5 molecule of cardiolipin per molecule of subunit I. Lipoprotein staining of sodium dodecyl sulfate/urea/acrylamide gels of cytochrome oxidase support the findings that subunit I is a lipoprotein. The resistance of this tightly bound cardiolipin to organic solvent extraction suggests a specific association of some tenacity with the protein. PMID- 6253461 TI - Unmasking effect of alamethicin on the (Na+,K+)-ATPase, beta-adrenergic receptor coupled adenylate cyclase, and cAMP-dependent protein kinase activities of cardiac sarcolemmal vesicles. AB - A mechanism for the activating effect of alamethicin on membrane enzymes was investigated, using a purified preparation of cardiac sarcolemmal vesicles. (Na+,K+)-ATPase, beta-adrenergic receptor-coupled adenylate cyclase, and cAMP dependent protein kinase activities were measured. alamethicin increased ouabain sensitive (Na+,K+)-ATPase activity of sarcolemmal vesicles 5- to 7-fold and adenylate cyclase activity 2.5- to 4-fold. Adenylate cyclase retained its sensitivity to the beta-adrenergic agonist isoproterenol after membranes were treated with alamethicin. Alamethicin caused a 4- to 6-fold increase in the number of detectable (Na+,K+)-ATPase enzymic sites, but no increase ws noted for the number of muscarinic-cholinergic receptor-binding sites. Phosphorylation of endogenous proteins of sarcolemmal vesicles by an intrinsic cAMP-dependent protein kinase activity was stimulated 5- to 7-fold by alamethicin. The regulatory subunit of the membrane-bound cAMP-dependent protein kinase was labeled with the photoaffinity probe 8-azido-adenosine 3':5'[32P]monophosphate (8 N3-[32P]cAMP), and it migrated with an apparent molecular weight of 55,000 in sodium dodecyl sulfate polyacrylamide gels. Alamethicin stimulated autophosphorylation of the regulatory subunit by [gamma-32P]ATP 6-fold and incorporation of of 8-N3-[32P]cAMP into the subunit 2.6-fold. The results suggest that alamethicin disrupts membrane barriers of sarcolemmal vesicles, which are mostly right side out, giving substrates and activators access to enzymic sites in the interior of the vesicles, while preserving functional coupling of enzymes to their effectors. PMID- 6253463 TI - Inhibition of leukotriene biosynthesis by the leukocyte product 15-hydroxy 5,8,11,13-eicosatetraenoic acid. AB - Rabbit peritoneal polymorphonuclear leukocytes, elicited with glycogen, metabolized added [1-14C]arachidonic acid to the 5-lipoxygenase products 5 hydroxy-6,8,11,14-eicosatetraenoic acid and 5,12-dihydroxy-6,8,10,14 eicosatetraenoic acid (leukotriene B) and the 15-lipoxygenase product 15-hydroxy 5,8,11,13-eicosatetraenoic acid. These metabolites were isolated by high pressure liquid chromatography and converted to the trimethylsilyl-ether methyl ester derivatives, and the structures were confirmed by gas chromatography-mass spectrometry. When polymorphonuclear leukocytes were preincubated with 15-HETE (16 microM), the formation of 5-hydroxy-6,8,11,14-eicosatetraenoic acid and 5,12 dihydroxy-6,8,10,14-eicostatetraenoic acid from [1-14C]arachidonic acid was strongly suppressed. The concentration required for 50% inhibition of the 5 lipoxygenase pathway in these cells was approximately 6 microM, which is comparable to the concentrations (0.20 to 1.8 microM) of 15-hydroxy-5,8,11,13 eicosatetraenoic acid produced in incubations of polymorphonuclear leukocytes with arachidonic acid alone. Recent reports indicate that slow-reacting substance of anaphylaxis (leukotriene C/D) and chemotactic substance leukotriene B are arachidonic acid metabolites formed via the 5-lipoxygenase pathway. Our observations thus suggest that 15-hydroxy-5,8,11,13-eicosatetraenoic acid can regulate the formation of these vasoactive and inflammatory mediators intracellularly. PMID- 6253462 TI - Identification of endogenous substrate proteins for cAMP-dependent protein kinase in bovine brain. PMID- 6253464 TI - Characterization of a specific, high affinity binding macromolecule for 1 alpha, 25-dihydroxyvitamin D3 in cultured chick kidney cells. AB - Cytosol prepared from vitamin D3-deficient kidney cells in culture contains a 3.7 S protein that specifically binds 1,25-dihydroxyvitamin D3 with high affinity and low capacity. Whole kidney homogenate cytosol preparations are shown to possess two 1,25-dihydroxyvitamin D3 binding macromolecules. One of the binding proteins sediments at 3.5 to 3.7 S while the second sediments at 6.0 S. The 6.0 S component has a greater affinity for 25-dihydroxyvitamin D3 than for 1,25 dihydroxyvitamin D3. Cultured cell cytosol was found to have little 6.0 S 25 hydroxyvitamin D3 binding protein. Scatchard analysis of the cultured cell cytosol reveals an equilibrium binding constant (KD) of 5.6 x 10 (-11) with 57 fmol of sites/mg of protein. The receptor-like protein has a Mr = 72,000 and as with other steroid receptors it aggregates in the presence of low potassium concentrations. Analog competition for receptor binding reveals the following potency order: 1,25-dihydroxyvitamin D3 > 25-hydroxyvitamin D3 > 1 alpha hydroxyvitamin D3 > 24(R),25-dihydroxyvitamin D3; the receptor had no detectable affinity for vitamin D3. The kidney cells respond to 1,25-dihydroxyvitamin D3 by diminishing 25-hydroxyvitamin D3 1 alpha-hydroxylation and increasing 24R hydroxylation. Cultured cells provide a preparation of cytosol which has allowed extensive characterization of the renal 1,25-dihydroxyvitamin D3 receptor and should facilitate investigations into the role this receptor plays in renal control of vitamin D3 metabolism. PMID- 6253465 TI - Parathyroid hormone . renal receptor interactions. Demonstration of two receptor binding domains. PMID- 6253466 TI - Effects of cholestyramine on receptor-mediated plasma clearance and tissue uptake of human low density lipoproteins in the rabbit. AB - This study examines the effects of cholestyramine (2 g/day) on the plasma clearance and tissue uptake of human low density lipoprotein (LDL) in rabbits. 1,2-Cyclohexanedione modification of human LDL abolishes its recognition by high affinity cell membrane receptors in vitro and delays its plasma clearance in comparison to native LDL. Consequently, the difference between the fractional rates of catabolism of simultaneously injected native and cyclohexanedione treated LDL is an index of in vivo receptor-mediated clearance of the lipoprotein. When human 125I-LDL and 131I-cyclohexanedione-treated LDL were injected into rabbits, 44% of the lipoprotein was cleared from the plasma by the receptor mechanism. Various tissues were removed from the animals at the end of the turnover study and their relative uptakes of 125I native and 131I cyclohexanedione-treated LDL were measured. All exhibited receptor activity to some extent, incorporating more native than cyclohexanedione-modified LDL. The greatest receptor activity per g of tissue was found in lymph nodes, spleen, and liver and, in terms of whole organ uptake, the liver played a major role in LDL catabolism. Treatment of the rabbits with cholestyramine lowered the circulating LDL cholesterol level by promoting its clearance (120%, p < 0.001) via the receptor pathway. This was associated with a virtual doubling of receptor mediated incorporation of the lipoprotein into the liver. These results suggest that the drain which cholestyramine induces in the hepatic cholesterol pool promotes LDL receptor activity in this organ and thereby lowers the level of circulating LDL. PMID- 6253468 TI - Molecular interactions between thyroid hormone analogs and the rat liver nuclear receptor. Partitioning of equilibrium binding free energy changes into substituent group interactions. PMID- 6253467 TI - Interaction of mammalian deoxyribonuclease V, a double strand 3' to 5' and 5' to 3' exonuclease, with deoxyribonucleic acid polymerase-beta from the Novikoff hepatoma. AB - Novikoff hepatoma stimulatory factor IV has been resolved from the DNA polymerase beta on a single-stranded DNA-cellulose column and then purified to > 95% homogeneity on hydroxylapatite. A single band of Mr = 12,000 is found on sodium dodecyl sulfate-polyacrylamide gels. Addition of factor IV to a DNA synthesis reaction causes (i) an increase in initial velocity, (ii) a prolongation of linear synthesis, and (iii) an increase in extent of incorporation. In the absence of factor IV, the reaction reaches a plateau in approximately 1 h. Factor IV, added at this point, causes resumption of synthesis with kinetics similar to when factor IV was present from the start. When factor IV is present, synthesis is followed by DNA degradation, indicating nuclease activity. Factor IV is shown to be an exonuclease which hydrolyzes double-stranded substrates in both the 3' to 5' and 5' to 3' directions at similar rates. Factor IV interacts with the 3.3 S beta-polymerase forming an aggregate sedimenting at 4.1 S and containing both polymerase and exonuclease activities. Analysis of fractions containing a beta polymerase . exonuclease complex on polyacrylamide gels suggests a stoichiometry of 1:1. The exonuclease shows a strong preference for double-stranded substrates and is most active on poly(dA-dT). It can hydrolyze chains containing either a 3' or 5'-phosphoryl or a 5'- or 3'-hydroxyl terminus. The product of digestion is predominantly 5'-nucleoside monophosphates. The enzyme cannot hydrolyze di- or trinucleotides, lacks RNase-H activity, and will not liberate thymine dimers from UV-irradiated DNA. The exonuclease has an alkaline pH optimum and requires a divalent cation. Since the properties of this exonuclease are unlike those of previously described mammalian DNases, we have named this enzyme mammalian DNase V. PMID- 6253470 TI - A hypothetical model of the cytochrome c peroxidase . cytochrome c electron transfer complex. AB - A hypothetical three-dimensional model of the cytochrome c peroxidase . tuna cytochrome c complex is presented. The model is based on known x-ray structures and supported by chemical modification and kinetic data. Cytochrome c peroxidase contains a ring of aspartate residues with a spatial distribution on the molecular surface that is complementary to the distribution of highly conserved lysines surrounding the exposed edge of the cytochrome c heme crevice, namely lysines 13, 27, 72, 86, and 87. These lysines are known to play a functional role in the reaction with cytochrome c peroxidase, cytochrome oxidase, cytochrome c1, and cytochrome b5. A hypothetical model of the complex was constructed with the aid of a computer-graphics display system by visually optimizing hydrogen bonding interactions between complementary charged groups. The two hemes in the resulting model are parallel with an edge separation of 16.5 A. In addition, a system of inter- and intramolecular pi-pi and hydrogen bonding interactions forms a bridge between the hemes and suggests a mechanism of electron transfer. PMID- 6253469 TI - Regulation of hormone-receptor coupling to adenylyl cyclase. Effects of GTP and GDP. AB - GDP and GTP regulation of receptor-mediated stimulation of adenylyl cyclases in membranes of S49 murine lymphoma cells (S49), NS-20 murine neuroblastoma cells (NS-20), rabbit corpora lutea (CL), and turkey erythrocytes were studied under assay conditions which minimized conversion of added GTP to GDP and of added GDP to GTP. Hormonal stimulation in all systems required guanine nucleotide addition. In the presence of GTP, adenylyl cyclase activity in S49, NS-20, and CL was stimulated respectively by isoproterenol and prostaglandin E1 (PGE1), by PGE1 and the adenosine analog, phenylisopropyladenosine, and by PGE1 and isoproterenol, with the first of the listed stimulants eliciting higher activities than the second. Activity in turkey erythrocyte membranes was stimulated by isoproterenol. GDP was partially effective in promoting hormonal stimulation, being able to sustain stimulation by isoproterenol and PGE1 in S49 cell membranes and by PGE1 in CL membranes. In NS-20 membranes, both GDP and guanosine-5'-O-(2 thiodiphosphate) (GDP beta S) were inhibitory on basal activity, yet promoted limited but significant stimulation by PGE1. In turkey erythrocytes, stimulation by isoproterenol could not be elicited with GDP or GDP beta S. Thus, although less effective than GTP in promoting hormonal stimulation of several adenylyl cyclase systems, GDP was clearly not inactive. Concentration effect curves for active hormone in the presence of GDP had higher apparent Ka values than in the presence of GTP. In spite of differences between the effects of GTP and GDP on hormonal stimulation of adenylyl cyclase activities, GTP and GDP affected equally well isoproterenol binding, regardless of whether or not its receptor could be shown to stimulate adenylyl cyclase in the presence of GDP. Determination of transphosphorylation of GDP to GTP showed that at saturating concentrations, the proportion of GDP converted to GTP is negligible and unaffected by hormonal stimulation. Concentrations giving 50% inhibition were determined for GTP- and GDP-mediated inhibition of guanyl-5'-yl imidodiphosphate stimulation in the absence and presence of stimulatory hormones. In all four systems studied, GTP and GDP interacted with about equal potency and hormonal stimulation was not accompanied by a selective decrease in affinity for GDP. One way to explain all of the results obtained is to view hormonally sensitive adenylyl cyclase systems as two-state enzymes whose activities are regulated by GTP and GDP through an allosteric site related to the catalytic moiety, and receptors as entities that are inactive and hence unable to couple unless occupied by hormones and activated by any guanine nucleotide through a distinct receptor-related process. PMID- 6253471 TI - 18O-Labeling of guanosine monophosphate upon hydrolysis of cyclic guanosine 3':5' monophosphate by phosphodiesterase. AB - The hydrolysis of cGMP by phosphodiesterase was conducted in [18O]water to determine the site of bond cleavage and the stoichiometry of 18O incorporation into 5'-GMP. Three different forms of phosphodiesterase including a calmodulin calcium-dependent enzyme in its basal and activated states were examined. The hydrolysis of cGMP catalyzed by each of the forms of phosphodiesterase proceeded with incorporation of 1 18O atom recoverable in the phosphate moiety of each molecule of 5'-GMP generated. No molecular species of phosphate deriving from the 5'-GMP generated containing two or three 18O were detectable. These results indicate that the phosphodiesterase-catalyzed hydrolysis of cGMP proceeds by nucleophilic substitution at phosphorus resulting in P-O bond cleavage. The stoichiometry of 18O incorporation indicates that the reaction proceeds without phosphate-water oxygen exchange when the hydrolytic reaction is catalyzed by diverse forms of phosphodiesterase in the basal or activated state. These considerations of the phosphodiesterase reaction help to establish the validity of monitoring the rate of enzyme-catalyzed hydrolysis of cGMP as a function of the rate of 18O-labeling of the phosphate of 5'-GMP when the reaction proceeds in a medium of predetermined 18O enrichment. PMID- 6253472 TI - Phosphorylation of heart glycogen synthase by cAMP-dependent protein kinase. Regulatory effects of ATP. AB - Glycogen synthase I, purified from bovine heart, had a specific activity of 33 units/mg and gave a single band on sodium dodecyl sulfate gel electrophoresis with a subunit molecular weight of 86,000. The enzyme was phosphorylated with cAMP-dependent protein kinase catalytic subunit, also isolated from heart. With 10 microM ATP, only one phosphate group was incorporated per subunit of glycogen synthase. The phosphorylation decreased the per cent of glycogen synthase I from 0.95 to 0.50 when activity was determined by assays with Na2SO4 and glucose 6 phosphate. Glycogen synthase containing one phosphate per subunit was designated GS-1. One additional phosphate was incorporated per synthase subunit when ATP was increased to 0.5 mM and the percent glycogen synthase I decreased from 0.50 to < 0.05. This enzyme form was designated GS-1,2. Conversion of GS-1 to Gs-1,2 gave cooperative kinetics with ATP concentration and a half-maximal stimulation at approximately 40 microM. Phosphorylation of GS-1 could also be achieved by adding other non-substrate nucleotide triphosphates such as ITP and UTP along with 10 microM ATP. Glucose-6-P and Na2SO4 were without effect on this phosphorylation reaction. Two separate peptides were obtained after CNBr cleavage of 32P-labeled GS-1,2 and only one from GS-1. Both enzyme forms contained a single phosphorylated peptide in common. Thus, heart glycogen synthase may be phosphorylated specifically in either of two different sites using appropriate concentrations of ATP. ATP acts as a substrate for the protein kinase and also affects the availability of a second site to phosphorylation by cAMP-dependent protein kinase. PMID- 6253473 TI - Evidence for the participation of independent translocation for phosphate and glucose 6-phosphate in the microsomal glucose-6-phosphatase system. Interactions of the system with orthophosphate, inorganic pyrophosphate, and carbamyl phosphate. AB - The interactions of Pi, PPi, and carbamyl-P with the hepatic glucose-6 phosphatase system were studied in intact and detergent-disrupted microsomes. Penetration of PPi and carbamyl-P into intact microsomes was evidenced by their reactions with the enzyme located exclusively on the luminal surface. Lack of effects of carbonyl cyanide m-chlorophenylhydrazone and valinomycin + KCl indicated that pH gradients and/or membrane potentials that could influence the kinetics of the system are not generated during metabolism of PPi and glucose-6-P by intact microsomes. With disrupted microsomes, only competitive interactions were seen among glucose-6-P, Pi, PPi, and carbamyl-P. With intact microsomes, Pi, PPi, and carbamyl-P were relatively weak, noncompetitive inhibitors of glucose-6 phosphatase, and PPi hydrolysis was inhibited competitively by Pi and carbamyl-P but noncompetitively by glucose-6-P. Analysis of the kinetic data in combination with findings from other studies that a variety of inhibitors of the glucose-6-P translocase (T1) does not affect PPi hydrolysis provide compelling evidence that permeability of microsomes to Pi, PPi, and carbamyl-P is mediated by a second translocase (T2). Some properties of the microsomal anion transporters are described. If the characteristics of the glucose-6-phosphatase system as presently defined in intact microsomes apply in vivo, glucose-6-P hydrolysis appears to be the predominant, if not the exclusive, physiologic function of the system. Both the "noncompetitive character" and the relative ineffectiveness of Pi as an inhibitor of glucose-6-phosphatase of intact microsomes result from the rate limitation imposed by T1 that prevents equilibration of glucose-6-P across the membrane. In microsomes from fed rats, where T1 is less rate restricting, about one-half as much Pi was required to give 50% inhibition compared with microsomes from fasted or diabetic rats. Thus, any treatment or agent that alters the kinetic relationship between transport and hydrolysis of glucose-6-P (e.g. endocrine or nutritional status) is an essential consideration in analyses of kinetic data for the glucose-6-phosphatase system. PMID- 6253474 TI - Introduction of liposome-encapsulated SV40 DNA into cells. AB - DNA, isolated from Simian virus 40 (SV40), has been encapsulated in large (0.4 micrometer diameter) unilamellar phospholipid vesicles. The procedure used for liposome preparation encapsulated the SV40 DNA at high efficiency (30 to 50% entrapment) and did not alter the physical or biological properties of the DNA molecules. The biological activity of the liposome-entrapped viral DNA was determined by plaque assays on a permissive monkey cell line. The infectivity of liposome-entrapped SV40 DNA was enhanced at least 100-fold over that of free naked DNA. Importantly, the infectivity of vesicle-entrapped DNA was resistant to DNase digestion, dependent on the amount of DNA encapsulated per vesicle and on the vesicle lipid composition. Liposomes composed of phosphatidylserine were the most efficient for delivery of DNA to cells (1.8 x 10(3) plaque-forming units/micrograms of DNA). Following the incubation of DNA-containing liposomes with cells, their infectivity could be enhanced an additional 10- to 200-fold by exposing the cells to high concentrations of polyethylene glycol or glycerol. Under these conditions the infectivity of liposome-encapsulated SV40 DNA (3 x 10(5) plaque-forming units/microgram) was comparable with values reported using the calcium phosphate method. In addition to providing a sensitive assay for monitoring and optimizing the delivery of vesicle contents to cells, the liposome mediated delivery of nucleic acids may have potential for increasing the efficiency of DNA delivery to cells and for extending the number of cell types which can be transformed or transfected. PMID- 6253475 TI - Further evidence that desensitization of beta-adrenergic-sensitive adenylate cyclase proceeds in two steps. Modification of the coupling and loss of beta adrenergic receptors. PMID- 6253476 TI - The estradiol-stimulated lipoprotein receptor of rat liver. A binding site that membrane mediates the uptake of rat lipoproteins containing apoproteins B and E. AB - Hepatic catabolism of lipoproteins containing apolipoproteins B or E is enhanced in rats treated with pharmacologic doses of 17 alpha-ethinyl estradiol. Liver membranes prepared from these rats exhibit an increased number of receptor sites that bind 125I-labeled human low density lipoproteins (LDL) in vitro. In the present studies, this estradiol-stimulated hepatic receptor was shown to recognize the following rat lipoproteins: LDL, very low density lipoproteins obtained from liver perfusates (hepatic VLDL), and VLDL-remnants prepared by intravenous injection of hepatic VLDL into functionally eviscerated rats. The receptor also recognized synthetic lamellar complexes of lecithin and rat apoprotein E as well as canine high density lipoproteins containing apoprotein E (apo E-HDLc). It did not recognize human HDL or rat HDL deficient in apoprotein E. Much smaller amounts of this high affinity binding site were also found on liver membranes from untreated rats, the number of such sites increasing more than 10-fold after the animals were treated with estradiol. Each of the rat lipoproteins recognized by this receptor was taken up more rapidly by perfused livers from estrogen-treated rats. In addition, enrichment of hepatic VLDL with C apoproteins lowered the ability of these lipoproteins to bind to the estradiol stimulated receptor and diminished their rate of uptake by the perfused liver of estrogen-treated rats, just as it did in normal rats. The current data indicate that under the influence of pharmacologic doses of estradiol the liver of the rat contains increased amounts of a functional lipoprotein receptor that binds lipoproteins containing apoproteins B and E. This hepatic lipoprotein receptor appears to mediate the uptake and degradation of lipoproteins by the normal liver as well as the liver of estradiol-treated rats. The hepatic receptor bears a close functional resemblance to the LDL receptor previously characterized on extrahepatic cells. PMID- 6253477 TI - Poly(ADP-ribose) synthesis in vitro programmed by damaged DNA. A comparison of DNA molecules containing different types of strand breaks. AB - The ability of DNA is support poly(ADP-ribose) synthesis is completely dependent upon the number and type of strand breaks it contains and is independent of the sequence. Single-stranded DNA is ineffective. Covalently closed circular plasmid DNA is ineffective, but when it is enzymatically digested it activates poly(ADP ribose) polymerase in proportion to the number of strand breaks, suggesting that the polymerase recognizes DNA ends. Double-stranded restriction fragments with flush ends are approximately 3 times more effective than are fragments with unpaired nucleotides extending from the 3' termini and about 10 times more effective than are either fragments with unpaired nucleotides extending from the 5' termini or plasmids with single-strand breaks. All types of restriction fragments become more effective upon removal of terminal 5'-phosphate groups. This specificity profile may relate to the proposed role of poly(ADP-ribose) synthesis in the repair of DNA strand breaks, for those which are assumed to be more difficult to repair in vivo are the more effective stimulators. Poly(ADP ribose) polymerase has no divalent cation requirement when supplied with flush ended DNA fragments, but magnesium may enhance the effective of other types of DNA by activating magnesium-dependent nucleases. Ineffective DNAs, such as covalently closed plasmids or synthetic homopolymers that are unable to form Watson-Crick duplexes, apparently compete with effective DNA and weakly inhibit poly(ADP-ribose) synthesis. PMID- 6253478 TI - Assembly and disassembly properties of microtubules formed in the presence of GTP, 5'-guanylyl imidodiphosphate, and 5'-guanylyl methylenediphosphate. AB - We have examined the properties of microtubules formed in the presence of GTP, 5' guanylyl imidodiphosphate (GMPP(NH)P), and 5'-guanylyl methylenediphosphate (GMPP(CH2)P) to identify features of the assembly or disassembly reactions uniquely related to hydrolysis. The assembly of microtubules with GTP or GMPP(NH)P was similar in terms of rates and extents of assembly, the length distributions, and podophyllotoxin-induced depolymerization. The greater rapidity of GMPP(CH2)P-supported assembly, however, resulted in shorter, more numerous microtubules and the rate of podophyllotoxin-induced depolymerization was consistent with an increased number of concentration of microtubules. Experiments with GTP or analogue incorporation and release indicated that GTP-tubule turnover corresponded to a rate of about 8% of the microtubule protein taken up or released per h. With GMPP(NH)P- and GMPP(CH2)P-tubules, the rates of label uptake by unlabeled microtubules were considerably lower than observed with guanosine triphosphate. We suggest that exchange experiments can reflect contributions from head-to-tail polymerization and polymer length redistribution, but it is not as yet possible to evaluate the relative contributions of each process. PMID- 6253479 TI - An endonuclease activity of chicken erythrocyte nuclei and mononucleosomes. AB - Endogenous nuclease is present in the nuclear sap of chicken erythrocyte nuclei. This enzyme resembles the nuclease of mammalian nuclei in requirements for bivalent cations and in production of large chromatin fragments that gradually decrease in size, but differs in that the products do not go through the stage of discrete bands on gel electrophoresis. Endogenous nuclease and micrococcal nuclease are also detectable in mononucleosomes prepared from chicken erythrocytes with the aid of micrococcal nuclease. Both nucleases are extractable with 0.35 M NaCl, and both are inhibited by pTp. In the absence of Ca2+, the micrococcal nuclease is totally inactive, whereas the endogenous nuclease shows a low level of activity. PMID- 6253480 TI - Chromatin conjugate protein A24 is cleaved and ubiquitin is lost during chicken erythropoiesis. AB - The content of protein A24, an adduct of histone 2A and ubiquitin, was studied during chicken erythropoiesis. The amount of protein A24 was negligible in transcriptionally inactive mature chicken erythrocyte nuclei and 6-fold higher in the transcriptionally active nuclei of erythroid cells from phenylhydrazine treated chickens. The decreased amount of protein A24 in the mature cells was offset by the relatively increased amount of histone 2A. A loss of free ubiquitin was also noted. In contrast, the amounts of high mobility group proteins 1,2, and E were essentially constant. Inasmuch as cleavage of the ubiquitin---histone 2A bond of protein A24 and loss of ubiquitin accompanied transcriptional shutdown during erythropoiesis, the presence of protein A24 and ubiquitin in premature polychromatic erythrocytes may reflect the presence of potentially active and transcribing chromatin structures. PMID- 6253481 TI - Mapping of mitochondrial structural genes in Neurospora crassa. AB - A hybridization method has been employed to study the organization of the mitochondrial genome of Neurospora crassa. The method involves the use of 5' end labeled single-stranded restriction fragments obtained from cytoplasmic "petite" strains of Saccharomyces cerevisiae known to contain single mitochondrial genes. The presence and localization of genes homologous to Subunits 1, 2, and 3 of cytochrome oxidase, cytochrome b and Subunit 6 of the ATPase is thus established for the mitochondrial genome of N. crassa. PMID- 6253482 TI - Size characteristics of the solubilized saxitoxin receptor of the voltage sensitive sodium channel from rat brain. AB - The saxitoxin receptor of the voltage-sensitive sodium channel from rat brain was solubilized with Triton X-100 and stabilized with phosphatidylcholine. The size characteristics of the detergent . phospholipid . receptor complex were studied by gel filtration and sucrose gradient sedimentation in H2O and D2O. The complex has Stokes radius = 80 A, S20,W = 12 S, v = 0.82 ml/ g, and Mr = 601,000 +/- 48,000. Assuming v = 0.73 ml/g for the saxitoxin receptor protein, the mass of the complex consists of 47.4% detergent and phosphatidylcholine and 52.6% saxitoxin receptor protein with Mr = 316,000 +/- 63,000. PMID- 6253483 TI - Regulation of phosphatidylcholine biosynthesis in cultured chick embryonic muscle treated with phospholipase C. AB - Cultures of embryonic chick muscle cells grown in medium containing phospholipase C from Clostridium perfringens incorporated [3H]choline into lipid at a rate 3- to 5-fold higher than control cultures. To determine the mechanism by which stimulation of phosphatidylcholine synthesis occurred in phospholipase C-treated cells, activities of enzymes and levels of intermediates in the biosynthetic pathway for phosphatidylcholine were examined. Activities of choline kinase, choline phosphotransferase, glycerol-3-phosphate dehydrogenase, glycerol-3 phosphate acyltransferase, acylglycerol-3-phosphate acyltransferase, and phosphatidic acid phosphatase in phospholipase C-treated cells were the same or only slightly higher than in control cells. CTP:phosphocholine cytidylyltransferase, on the other hand, was 3 times as active in homogenates from phospholipase C-treated cells. Levels of phosphocholine decreased and levels of CDP-choline increased in phospholipase C-treated cells, and a calculation of the disequilibrium ratio indicated that the cytidylyltransferase reaction was not at equilibrium. The cytidylyltransferase was, thus, identified as the regulatory enzyme for choline flux in these cells. The cytidylyltransferase was located in both the cytosolic and particulate fractions from cultured muscle cells and a much larger portion of enzyme activity was associated with the particulate fraction in cells treated with phospholipase C. Sonicated preparations of total chick lipids, phosphatidylethanolamine, and phosphatidylserine greatly stimulated the cytosolic cytidylyltransferase activity but had no effect on the particulate enzyme. Neither stimulation of incorporation of [3H]choline into lipid nor activation of the cytidylyltransferase was dependent on protein synthesis. A model for the mechanism of regulation of phosphatidylcholine synthesis in embryonic chick muscle is presented. PMID- 6253484 TI - The reconstituted (Na,K)-ATPase is electrogenic. PMID- 6253485 TI - Characterization of the receptor for epidermal growth factor-urogastrone in human placenta membranes. AB - The binding of mouse epidermal growth factor-urogastrone (EGF-URO) to membranes from term human placenta is peptide-specific, saturable (about 20 pmol of EGF-URO bound maximally/mg of protein), reversible, and of high affinity (KD about 400 pM). Optimal binding is observed at pH 7.6. At low pH (3.5 to 5.0). EGF-URO can be reversibly dissociated from the receptor; however, exposure to pH < 3 irreversibly inactivates the receptor. The binding, which does not exhibit ligand cooperativity, exhibits an association rate constant of 6.1 x 10(-4) s-1 and a dissociation rate constant of 6.1 x 10(-4) s-1. The dissociation constant determined from the rate constants, 240 pM, is in reasonable agreement with the constant estimated by equilibrium methods. Both monovalent and divalent cations augment EGF-URO binding 2- to 3-fold. Although in general, divalent cations enhance binding at lower concentrations (optimum, 5 mM) than do monovalent cations (optimum, approximately 80 mM), there is no cation-specific effect. Neither guanine nor adenine nucleotides affect EGF-URO binding. Whereas the proteolytic enzymes (trypsin, chymotrypsin, papain, and pepsin) inactivate the receptor, neuraminidase and phospholipases A2, C, and D augment EGF-URO binding. Neuraminidase increases the number of available sites without affecting ligand affinity. Wheat germ agglutinin, concanavalin A, and phytohemagglutinin all compete for the binding of EGF-URO. The data complement previous observations of EGF-URO binding obtained in intact cells and provide a basis for the solubilization, characterization, and isolation of this receptor from a rich tissue source. PMID- 6253486 TI - Solubilization and isolation of the human placenta receptor for epidermal growth factor-urogastrone. AB - We describe the solubilization and purification of both the photoaffinity-labeled and unlabeled human placenta receptor for epidermal growth factor-urogastrone (EGF-URO). The photolabeled receptor can be purified 300- to 500-fold from membrane extracts by combined immunoaffinity and lectin-agarose affinity chromatography. This isolation approaches theoretical purity. Upon gel filtration and wheat germ agglutinin-Sepharose chromatography, the photolabeled receptor and the EGF-URO binding activity co-migrate, as measured by a newly developed lectin agarose immobilization assay of receptor binding. Sequential ion exchange, Cibacron blue-Sepharose, wheat germ agglutinin-Sepharose, and gel filtration chromatography yield a 110-fold purification of the EGF-URO binding activity; this purified fraction contains protein constituents that exhibit electrophoretic mobilities parallel to those of the photolabeled receptor constituents, that have apparent molecular weights of 180,000 and 160,000. This molecular weight range is consistent with a measured apparent Stokes radius for both the photolabeled and unlabeled receptor of 5.1 nm (Sephacryl S-200 gel filtration), although an apparent radius of 4.3 nm is estimated by gel filtration on Sepharose-6B. The apparent molecular weight of the photolabeled receptor is unaffected by 2 mercaptoethanol. This work provides a basis for further detailed studies of this growth factor receptor. PMID- 6253488 TI - Intestinal membrane calcium-binding protein. Vitamin D-dependent membrane component of the intestinal calcium transport mechanism. AB - A particulate fraction of rat intestinal mucosal homogenates, termed the "calcium binding complex," contains three vitamin D-dependent activities: calcium binding of high affinity, calcium-dependent adenosine triphosphatase, and p nitrophenylphosphatase. These particulate activities vary concordantly with intestinal calcium transport, suggesting that they represent membrane components of the translocation mechanism. The particulate was solubilized with 1-butanol and the activities were resolved partially by gel filtration and by DEAE cellulose and spheroidal hydroxyl-apatite column chromatography. The Ca-binding activity was separated from the enzymes and isolated as a protein of molecular weight approximately 200,000, as estimated by gel filtration in 0.1% Triton X 100. The membrane protein, named IMCal (intestinal membrane calcium-binding protein), was dissociated with sodium dodecyl sulfate to yield a monomer of molecular weight 20,500 which is clearly distinguishable from the soluble calcium binding protein (molecular weight 11,500) of rat mucosa. The apparent dissociation constants of Ca2+ of IMCal and of the soluble calcium-binding protein were estimated as 0.37 microM and 2.25 microM, respectively. The vitamin D-dependent activities of the calcium-binding complex are present in isolated intestinal microvillus membranes and may mediate the translocation of calcium from the intestinal lumen to the cytosol. PMID- 6253487 TI - Stabilization of proteins by guanidination. AB - Earlier studies have indicated the marked resistance of two pronase endopeptidases to denaturation in high concentrations of urea or guanidine hydrochloride (Siegel, S., and Awad, W. M., Jr. (1973) J. Biol. Chem. 248, 3233- 3240). One component has only a single residue of lysine and the other has none. The consideration arose that lysine-containing peptide segments may be less stable than those containing arginine because of the fluctuations of the side groups of the former residue. The small epsilon amino groups may not be able to sustain solvation of the hydrophobic arm in an aqueous medium. Arginine residues have shorter hydrophobic arms, larger hydrophilic groups, and higher pKa values and, thus may be less motile than lysine. The hypothesis was tested by guanidination of seven globular proteins (bovine carbonic anhydrase, chymotrypsinogen, alpha-lactalbumin, serum albumin, ribonuclease, hen egg lysozyme, and horse heart cytochrome c). Conversion of lysine residues to homoarginine was between 90 and 99%. Tritium-hydrogen isotope exchange revealed that all proteins except lysozyme demonstrated reduced out-exchange after guanidination. The results with lysozyme were not unexpected since only this protein has a high arginine to lysine ratio. These findings suggest that high arginine to lysine ratios contribute to protein stability. PMID- 6253489 TI - Independent mechanisms of adenosine activation and inhibition of the turkey erythrocyte adenylate cyclase system. PMID- 6253490 TI - The role of high density lipoproteins in rat adrenal cholesterol metabolism and steroidogenesis. AB - Addition of rat or human high density lipoproteins (HDL) or human low density lipoproteins (LDL) to rat adrenocortical cells in vitro was found to enhance steroid production and increase cell cholesterol content. These effects of HDL were not observed in cultured mouse Y-1 adrenal cells, suggesting that rat adrenal cells possess a specific mechanism for uptake of HDL cholesterol not found in Y-1 cells. The effects of HDL were most marked on cells previously stimulated with adrenocorticotropin (ACTH) and depleted of their endogenous cholesterol stores. Such cells were prepared either by treatment in vivo with 4 aminopyrazolopyrimidine or in vitro with ACTH (10(-7) M) in lipoprotein-poor media. Steroid production by treated cells exhibited a saturable dependence on media HDL concentration. In addition to enhancing ACTH stimulated steroid production, addition of HDL also resulted in a saturable concentration-dependent increase in cell cholesterol content. Both aminoglutethimide and cycloheximide were found to inhibit HDL-enhanced steroid production. Finally, addition of HDL to short term incubations (5 1/2 h) of ACTH-treated cells caused no change in the rate of incorporation of 14C-acetate into cholesterol or corticosterone. These results indicate that rat adrenocortical cells possess a specific, saturable, ACTH-dependent mechanism for uptake of HDL cholesterol. Moreover, cellular uptake of HDL cholesterol exceeded by at least 4-fold the amount of cholesterol associated with HDL apoprotein degraded by the cells, suggesting that utilization of HDL cholesterol does not require endocytosis and lysosomal degradation of the entire HDL particle. PMID- 6253491 TI - The effects of lithium ion and other agents on the activity of myo-inositol-1 phosphatase from bovine brain. AB - myo-Inositol-1-phosphatase has been partially purified from bovine brain. The enzyme has a molecular weight of about 58,000. Both L-myo-inositol 1-phosphate and D-myo-inositol 1-phosphate are hydrolyzed by the enzyme as well as (-)-chiro inositol 3-phosphate and 2'-AMP. Triphosphoinositide is not a substrate. The phosphatase is completely dependent on Mg2+, which has a Km of 1 mM. Calcium and manganese ions are competitive inhibitors of Mg2+ binding with Ki values of 18 microM and 2 microM, respectively. Lithium chloride inhibits the hydrolysis of both L- and D-myo-inositol 1-phosphate to the extent of 50% at a concentration of 0.8 mM. The phosphatase from testis is similarly inhibited by lithium. Lithium ion is a noncompetitive inhibitor of Mg2+ binding and an uncompetitive inhibitor of myo-inositol 1-phosphate binding. Because lithium chloride administration elicits both an increase in the levels of myo-inositol 1-phosphate and a decrease in the levels of myo-inositol in rat brain (Allison, 1978), and because these actions are blocked by anticholinergic agents, we examined the effects of cholinergic agonists and antagonists on the enzyme and found none. The possibility that the inhibition of this enzyme by lithium ion is related to the pharmacological actions of lithium is discussed. PMID- 6253492 TI - NMR studies of the nucleotide conformation and the arrangement of substrates and activators on phosphoribosylpyrophosphate synthetase. PMID- 6253493 TI - Insulin stimulation of (Na+,K+)-adenosine triphosphatase-dependent 86Rb+ uptake in rat adipocytes. AB - Insulin stimulated the uptake of 86Rb+ (a K+ analog) in rat adipocytes and increased the steady state concentration of intracellular potassium. Half-maximal stimulation occurred at an insulin concentration of 200 pM. Both basal- and insulin-stimulated 86Rb+ transport rates depended on the concentration of external K+, external Na+, and were 90% inhibited by 10(-3) M ouabain and 10(-3) M KCN, indicating that the hormone was activating the (Na+,K+)-ATPase. Insulin had no effect on the entry of 22Na+ or exit of 86Rb+. Kinetic analysis demonstrated that insulin acted by increasing the maximum velocity, Vmax, of 86Rb+ entry. Inhibition of the rate of Rb+ uptake by ouabain was best described by a biphasic inhibition curve. Scatchard analysis of ouabain binding to intact cells indicated binding sites with multiple affinities. Only the rubidium transport sites which exhibited a high affinity for ouabain were stimulated by insulin. Stimulation required insulin binding to an intact cell surface receptor, as it was reversible by trypsinization. We conclude that the uptake of 86Rb+ by the (Na+,K+)-ATPase is an insulin-sensitive membrane transport process in the fat cell. PMID- 6253495 TI - Induction of the fibrinogen receptor on human platelets by epinephrine and the combination of epinephrine and ADP. AB - The capacity of epinephrine alone and the combination of low dose epinephrine and ADP to support the binding of fibrinogen to washed human platelets has been examined, 125I-Fibrinogen was bound to epinephrine-stimulated platelets, but 90 min were required to achieve maximal binding at 22 degrees C in contrast to 20 to 30 min with ADP. The overall rate of interaction appeared to reflect the slow binding of fibrinogen to epinephrine-stimulated platelets as opposed to the rate of stimulation of the cell. Divalent ions were required for binding of fibrinogen to epinephrine-stimulated platelets, and both calcium and magnesium supported binding with a prolonged time course. Fibrinogen binding was maximally supported by 20 to 30 microM epinephrine. The combination of low dose epinephrine (5 microM) and low dose ADP (0.5 microM), which acted synergistically to induce platelet aggregation, supported the rapid (10 min) binding of fibrinogen to platelets. With 4 microM epinephrine, more fibrinogen bound per platelet at all ADP doses than with ADP alone. With all the stimuli, saturable binding of fibrinogen to the platelet was observed, and Scatchard plots were linear, yielding very similar apparent association constants. The number of molecules bound per cell was stimulus-dependent, with 30 microM epinephrine inducing the binding of fewer fibrinogen molecules per cell (mean = 20,400) than 10 microM ADP (mean = 35,900) or the combination of 5 microM epinephrine + 0.5 microM ADP (mean = 43,600). The participation of endogenous ADP in fibrinogen binding to epinephrine-stimulated platelets was suggested since enzymes which remove ADP, apyrase, and creatine phosphate/creatine phosphokinase, and the ADP analogue, 2 chloroadenosine, completely inhibited the binding of fibrinogen to the platelet. PMID- 6253494 TI - The role of lysine-41 of ribonuclease A in the interaction with RNase inhibitor from human placenta. AB - 3-N-Carboxymethyl-His-12 and 1-N-carboxymethyl-His-119-RNase A bind to the naturally occurring RNase inhibitor, isolated from human placenta, 1.3 and 3.6 times, respectively, more strongly than does native RNase A. Near-ultraviolet circular dichroism measurements indicate that the conformational change which occurs upon carboxymethylation of either of the active site histidine residues appears different from that which the protein undergoes upon binding of substrate of a substrate analogue. Specific carboxymethylation of Lys-41 of RNase A decreased the strength of the interaction between the enzyme and the RNase inhibitor to about 12% of the initial value. The near-UV CD spectra of Cm-Lys-41 RNase A and of acetimidyl-RNase A (9.3 lysines modified) and carbamylated RNase A (3.0 lysines modified), which also have weaker interactions with RNase inhibitor of 25% and 10%, respectively, show a negative [theta]MRW identical to that of native RNase A at 275 nm but are altered in the positive [theta]MRW at 240 nm. The CD measurements suggest that one or more tyrosine residues of RNase A may be involved in the interaction with inhibitor. The effects of pH and salt concentration suggest that a major part of the protein-protein interaction is probably through nonpolar forces. The strengths of interactions between the inhibitor and pancreatic RNases from several species were very similar. Since Tyr 92 is the only tyrosine residue retained in all of the species studied, this residue may have a key role in the nonpolar interaction. The data presented herein suggest that the interaction between RNase A and the inhibitor involves the positively charged epsilon-NH2 group of Lys-41 of RNase A. This interaction could result in the inactivation of the enzyme. PMID- 6253496 TI - Euglena gracilis chloroplast ribosomal RNA transcription units. I. The location of transfer RNA, 5 S, 16 S, and 23 S ribosomal RNA genes. AB - The organization of the genes in the rRNA coding region of Euglene gracilis Pringsheim strain Z chloroplast DNA has been determined. 125I labeled 16 S rRNA, 125I labeled 23 S rRNA, and [32P]tRNAs were hybridized to restriction nuclease fragments from cloned chloroplast DNA segments. The coding regions for 16 S and 23 S rRNAs have been located to within 1.75 and 3.1 kbp, respectively. Transfer rRNA genes are located in the 16 S to 23 S rRNA spacer region. Ribosomal RNAs and tRNAs are encoded on the same DNA strand in the 6.2 kbp tandemly repeated rRNA gene region. The order of genes, which is repeated three times in chloroplast DNA, is 16 S rRNA--tRNAS--23 S rRNA--5 S rRNA. Each set of genes is clustered in a region of 5.0 kbp. The organization and size of the genes is as expected if they are all part of a single transcription unit. PMID- 6253497 TI - Euglena gracilis chloroplast ribosomal RNA transcription units. II. Nucleotide sequence homology between the 16 S--23 S ribosomal RNA spacer and the 16 S ribosomal RNA leader regions. AB - The DNA sequences of two segments of the ribosomal RNA transcription units of Euglena gracilis Pringsheim strain Z chloroplast DNA have been determined. The first is from the 16 S to 23 S rRNA spacer region. The nucleotide sequence determined includes 64 bp from the 3'-end of the 16 S rRNA gene, the adjacent 87 bp spacer containing 68A-T base pairs, a tRNAIle gene, a 9-bp spacer, a tRNAAla gene, a spacer of approximately 15 bp, and the first 120 bp from the 5'-end of the 23 S rRNA gene. The gene organization of the 16 S to 23 S rRNA spacer, the identity of the tRNA genes, and the tRNA anticodons for the E. gracilis rRNA transcription units are identical with that of the rrnA, D, and X operons of Escherichia coli. The second DNA segment which was sequenced is from a region preceding the 5'-end of the 16 S rRNA gene. Within a continuous region of 189 bp in this 16 S rRNA leader sequence, 68% of the bases are homologous to the 16 S rRNA to 23 S rRNA spacer region. This homology includes the 3'-end of the 16 S rRNA gene, the adjacent spacer, and a complete "pseudo" tRNAIle gene. This leader sequence which has the same polarity as the rRNA transcripts, is flanked by nucleotide sequences resembling partial tRNA genes. PMID- 6253498 TI - Hormonal control of protein phosphorylation in turkey erythrocytes. Phosphorylation by cAMP-dependent and Ca2+-dependent protein kinases of distinct sites in goblin, a high molecular weight protein of the plasma membrane. AB - In previous studies, a correlation was observed between isoproterenol-responsive Na+-K+ co-transport in turkey erythrocytes and increased phosphorylation of goblin, an Mr = 230,000 protein of the turkey erythrocyte plasma membrane. The phosphorylation of specific sites in goblin has now been analyzed by tryptic fingerprinting. Three major phosphopeptides were detected in goblin prepared from intact, 32P-labeled erythrocytes. One of the peptides 1, was maximally phosphorylated in the absence of hormonal agents. Two additional peptides, 2 and 3, were phosphorylated only following exposure of cells to the beta-adrenergic agonist isoproterenol, to cAMP plus isobutylmethylxanthine, or to cholera toxin. In cells stimulated by isoproterenol, phosphorylation of goblin peptides 2 and 3 could be selectively and completely reversed by subsequent addition of the beta adrenergic antagonist propranolol. Addition of either cAMP or of Ca2+ plus calmodulin to purified turkey erythrocyte plasma membranes increased incorporation of 32P into goblin. Peptides 2 and 3 of goblin were phosphorylated by addition to the membranes of cAMP or of purified cAMP-dependent protein kinase. Two additional goblin peptides, 4 and 5, were phosphorylated in the plasma membrane preparation by addition of purified calmodulin plus Ca2+, whereas peptides 2 and 3 of goblin were not phosphorylated under these conditions. Peptide 1 did not incorporate 32P in the plasma membranes under any condition tested. Both calmodulin and cAMP-dependent protein kinase were identified directly in turkey erythrocytes. The three major phosphopeptides of goblin phosphorylated in intact cells (peptides 1, 2, and 3) contained phosphothreonine and represented distinct phosphorylation sites. In contrast, the two phosphopeptides of goblin phosphorylated in plasma membranes by addition of Ca+/calmodulin (peptides 4 and 5) contained phosphoserine. It is concluded that goblin, a plasma membrane protein possibly involved in the hormonal regulation of Na+-K+ co-transport, contains at least 3 distinct threonine residues and 1 or more serine residues which serve as specific substrates for three or more distinct protein kinases of the turkey erythrocyte, namely a cAMP-dependent enzyme, a Ca2+/calmodulin-dependent enzyme, and a third enzyme with undetermined regulatory control. PMID- 6253499 TI - H3-specific nucleohistone kinase of bovine thymus chromatin. Purification, characterization, and specificity for threonine residue 3. AB - Bovine thymus chromatin contains a cAMP-independent histone kinase which is entirely specific for a single site on H3 whether the histone substrate is soluble or associated with DNA in chromatin (Shoemaker, C. B., and Chalkley, R. (1978) J. Biol. Chem. 253, 5802--5807). The H3-kinase has been extracted, purified 2000-fold and extensively characterized. The purified enzyme produces a single band upon neutral gel electrophoresis and two distinct bands of 21,000 and 23,000 daltons upon sodium dodecyl sulfate-gel electrophoresis. Following subcellular fractionation, most or all of the enzymatic activity is associated with chromatin. Soluble histone inactivates H3-kinase after short incubations while a chromatin substrate permits the enzyme to remain active until H3 is fully phosphorylated. Assay conditions have been optimized in terms of pH and several cofactor concentrations. Optimal MgCl2 concentration occurs at 50 mM, while for MnCl2 the optimum is 300 microM. H3-kinase has a molecular weight of 38,000 as estimated by exclusion chromatography. The Km for ATP is 160 +/- 23 microM. The enzyme displays extraordinary substrate specificity for H3 histone as no other thymus protein has been observed as a substrate. Phosphorylation of H3 occurs at threonine residue 3. PMID- 6253500 TI - Primary hypophosphatemic rickets. Effect of oral phosphate and vitamin D on growth and surgical treatment. AB - Failure to diagnose and treat hypophosphatemic rickets during childhood resulted in stunted growth and progressive deformities of the lower limb. When the deformities were treated surgically, recurrent deformity and non-union of osteotomies developed, and further major opeative procedures were required to remedy these complications. Treatment from early childhood with oral phosphate and vitamin D improved the rate of growth and controlled the progression of bowleg deformity. Residual varus deformity was corrected by osteotomy through the proximal tibial metaphysis at skeletal maturity, when the results were predictable. Genu valgum deformity was corrected by stapling the medial part of the distal femoral epiphysis prior to skeletal maturity. With early postoperative mobilization and adequate medication, the complications of delayed tibial union and failure to correct the femoral valgus deformity were avoided. PMID- 6253501 TI - Molecular events in cells transformed by Rous Sarcoma virus. AB - The Rous sarcoma virus (RSV) transforming gene product has been identified and characterized as a phosphoprotein with a molecular weight of 60,000, denoted pp60src. Partially purified pp60src displays a closely associated phosphotransferase activity with the unusual specificity of phosphorylating tyrosine residues in a variety of proteins. That the enzymatic activity observed is actually encoded by the RSV-transforming gene is indicated by the comparison of the pp60src-protein kinase isolated from cells tranformed by a wild-type RSV or by a RSV temperature-sensitive transformation mutant; these experiments revealed that the latter enzyme had a half-life of 3 min at 41 degrees C, whereas that of the wild-type enzyme was 20 min. Evidence is now beginning to accumulate showing that viral pp60src expresses its protein kinase activity in transformed cells as well as in vitro because at least one cellular protein has been identified as a substrate for this activity of pp60src. Although the protein kinase activity associated with pp60src is itself cyclic AMP (cAMP) independent, the molecule contains at least one serine residue that is directly phosphorylated by the cellular cAMP-dependent protein kinase, thus suggesting that the viral transforming gene product may be regulated indirectly by the level of cAMP. The significance of this latter observation must be regarded from the point of view that the RSV src gene is apparently derived from a normal cellular gene that seemingly expresses in normal uninfected cells a phosphoprotein structurally and functionally closely related to pp60src. This celluar protein, found in all vertebrate species tested, also is a substrate for a cAMP-dependent protein kinase of normal cells, and, therefore, may be evolved to function in a regulatory circuit involving cAMP. PMID- 6253502 TI - Binding, internalization, and lysosomal association of 125I-human growth hormone in cultured human lymphocytes: a quantitative morphological and biochemical study. AB - 125I-human growth hormone (125I-hGH) binds specifically to receptors on cultures human lymphocytes (IM-9). When this process is studied by use of quantitative EM radioautography, under conditions of incubation at 15 degrees C for 5 min, the ligand is localized to the plasma membrane of the cell. At 30 degrees and 37 degrees C, however, 125I-hGH is progressively internalized by the cell as a function of time. The internalized ligand is found predominantly in the Golgi region of the cells, with a five-fold preferential localization to membrane bounded structures with the morphological and cytochemical characteristics of lysosomes. Up to 59% of these lysosome-like structures are positive for the acid phosphatase reaction under the conditions of incubation at 37 degrees C for 120 min. When the cell associated radioactivity after 15-120 min of incubation at 37 degrees C is extracted in 1 M acetic acid and filtered on a Sephadex G-100 column, 58-73% of the material elutes as intact hGH. When cells are incubated with 125I-hGH at 37 degrees C for 15-120 min, separated from the incubation medium, and washed and diluted 100-fold, the percent 125I-hGH dissociable decreases as a function of increasing time of incubation. When cells are incubated with 125I-hGH for 15 min at 37 degrees C and the radioactivity that dissociates from the cells during 15-90 min is studied, the labeled material appearing in the incubation medium is progressively degraded as a function of time of incubation. When the dissociation process is studied radioautographically, grains are found both in plasma membrane and intracelluar compartments after 30 min of association, but after 30 and 120 min of dissociation a higher proportion of grains are in the intracellular compartment. After 120 min of association, there is less dissociation from either compartment and a preferential increase of grains in the intracellular compartment. These data suggest that receptor-linked internalization of a polypeptide hormone provides a mechanism that couples degradation of the ligand with loss of the cell surface receptor. PMID- 6253503 TI - Induction of both rat and mouse lactate dehydrogenase in hybrids between inducible rat glioma and uninducible mouse neuroblastoma cells. AB - The specific activity of lactate dehydrogenase (LDH; EC 1.1.1.27) is induced two fold by l-norepinephrine (NE) in C6TK- rat glioma cells, but not in NA mouse neuroblastoma cells or various other nonglial cells. Previous reports have shown that the induction is mediated by cyclic AMP (cAMP) and possibly protein phosphorylation, and that it requires RNA and protein synthesis. To study the block to LDH induction in nonglial cells, we hybridized C6TK- cells with NA cells and isolated a hybrid clone in which LDH is inducible by NE. Mouse and rat LDH from hybrid cells were separated by electrophoresis and quantitated by two independent methods, and it was found that mouse and rat LDH were induced equally when cells were exposed to NE. The results suggest that inducibility of LDH is not determined by a cis-acting control at the gene level, but rather by the presence or absence of an earlier component in the cAMP-mediated induction system, and that the induction system acts indiscriminately on all active LDH gene copies in the cell. PMID- 6253504 TI - Hormonal regulation of amino acid transport and cAMP production in monolayer cultures of rat hepatocytes. AB - The effects of insulin, glucagon of Dexamethasone (DEX) and of glucagon with insulin or DEX were examined on the uptake of 2-amino [1-14C]isobutyric acid (AIB) and N-Methyl-2-amino [1-14C]isobutyric acid (NMe AIB) in monolayer cultures of rat hepatocytes. Insulin and glucagon stimulated the uptake of both the amino acids and DEX inhibited it, showing that all three of these hormones regulate the A system (the sodium-dependent system that permits the transport of NMe AIB) for amino acid transport in these cultures. Experiments investigating the transport of aminocyclopentane-1-carboxylic acid, 1- [carboxyl-14C] in the presence of excess AIB or in the absence of sodium showed that insulin had no effect on the activity of the L system (the sodium-independent system that prefers leucine). Experiments on the uptake of AIB in the presence of excess NMe AIB showed insulin had no effect on the transport activity of the ASC system (the sodium-dependent system that does not transport NMe AIB). Insulin concentrations ranging from 0.1 nM to 100 nM did not antagonize the stimulatory effect of optimum or suboptimum concentrations of glucagon on the uptake of either AIB or NMe AIB. Similarly, glucagon did not antagonize the stimulatory effect of optimum or suboptimum concentrations of insulin on the uptake of both the amino acids. The combined effect of insulin and glucagon was additive on the rate as well as the cumulative uptake of both AIB and NMe AIB. DEX alone inhibited the transport of both AIB and NMe AIB by about 25%, while glucagon caused a 2--3-fold increase; however, the addition of glucagon to cultures containing DEX caused a 7--8-fold increase in the uptake of both AIB and NMe AIB when compared to cultures containing DEX alone. The effect of insulin on the levels of cAMP was also investigated. Insulin had no effect on the cAMP levels in cultures treated or untreated with optimum or suboptimum concentrations of glucagon. PMID- 6253505 TI - Na entry and Na-K pump activity in murine, hamster, and human cells--effect of monensin, serum, platelet extract, and viral transformation. AB - The relationship between Na entry and the activity of the Na-K pump has been investigated in a variety of cell types by testing the effect of the Na ionophore monensin, mitogenic stimulation with serum and oncogenic transformation by SV40 and polyoma virus. We found that addition of monensin increases intracellular Na in quiescent cultures of murine, hamster, and human cells. In each case, the rise in intracellular Na by monensin is associated with an increase in the activity of the Na-K pump, which was measured as ouabain-inhibitable 86Rb uptake. The addition of serum to quiescent cultures stimulates 86Rb uptake in all cell types studied. Serum alone causes an increase in intracellular potassium with no consistent change in intracellular Na. In the presence of the Na-K pump inhibitor ouabain, serum causes a marked increase in intracellular Na, with little change in intracellular K. This pattern is interpreted as indicating that the primary effect of serum is to increase Na entry into the cells. A low concentration of monensin (0.2 micrograms/ml) mimics the effect of serum on ion fluxes and content, which supports the conclusion that serum and monensin stimulate 86Rb uptake in the same manner, namely by increasing Na entry into the cells. In addition, a partially purified platelet extract stimulates Na entry and 86Rb uptake in quiescent 3T3 cells. Finally 3T3 cells transformed by SV40 or polyoma virus exhibit a higher rate of Na entry and of Na-K pump activity than their untransformed 3T3 counterparts. All these results indicate that the rate of Na entry plays an important role in the regulation of the activity of the Na-K pump and that an increase in Na and K movements is a rapid response elicited by serum in a variety of cell types. PMID- 6253506 TI - Effects of insulin on glycogen metabolism of serum-deprived BHK-21 fibroblasts. AB - We have studied the effects of insulin on glycogen metabolism of cultured BHK-21 fibroblasts. Addition of insulin to cells cultured in 0.5% serum stimulated incorporation of 5mM 14C-glucose into glycogen and increased cellular glycogen content, without inducing proliferation. With serum-deprived cells incubated for 2 hr, maximal stimulation of incorporation of glucose into glycogen was 3.5-fold and the half-maximal dose of insulin was 5nM. After culture for 24 hr with 100nM insulin, incorporation was increased 13-fold and glycogen content was increased by 44%. Incorporation of glucose into glycogen was reduced by agents which elevate cellular adenosine 3',5-cyclic monophosphate (cyclic AMP): 10 microM prostaglandin E1 (PGE1), 0.25 mM 1-methyl-3-isobutylxanthine (MIX), 10 microM L epinephrine (L-EPI), and 10 microM L-isoproterenol (L-ISO). Culture with 100nM insulin for 2 hr stimulated incorporation three-fold in the presence of any of these compounds, but insulin did not affect cellular cyclic AMP. At all times from 1 hr to 24 hr after addition of insulin to serum-deprived cultures, the 1 min uptake of 10 microM 3H-2-deoxyglucose (3H-2DG) was increased. There were small (30 to 40%) increases in glycogen synthase I activity at 15 and 30 min but not 4 hr after addition of insulin. After 24 hr with insulin, total glycogen synthase and phosphorylase activities were increased approximately two-fold, without changes in their activation states. We conclude that insulin promotes glycogenesis in serum-deprived BHK-21 cells. This response is mediated principally by increased entry of glucose into cells, and is not mediated by a change in cellular cyclic AMP concentration. PMID- 6253508 TI - The stimulation of the initiation of DNA synthesis by fibroblast growth factor in Swiss 3T3 cells: interactions with hormones during the pre-replicative phase. AB - Fibroblast Growth Factor (FGF) stimulates quiescent Swiss 3T3 cells to initiate DNA synthesis and divide. Cells begin to enter the S-phase after a lag of 13--15 hr, and the rate of initiation of DNA synthesis in the population can be quantified by a first order rate constant, k. A subsaturating concentration of FGF may establish the lag phase, while the value of k is dependent on the FGF concentration present during the second half of the lag phase. Insulin and hydrocortisone enhance the effect of FGF by increasing k without changing the lag phase, and they can act when added at any time after FGF. Prostaglandin E1 (PGE1) causes a decrease in k and a lengthening of the lag phase, and acts only when added during the first 8 hr. None of these agents stimulate DNA synthesis in the absence of FGF. PMID- 6253507 TI - The effect of serum and multiplication stimulating activity on L6 myoblast growth: the lack of correlation with cyclic nucleotide changes. AB - The role of cAMP and cGMP in triggering proliferation of rat myoblasts was evaluated by: (1) measuring effects of mitogens on intracellular cyclic nucleotide levels, and (2) observing effects of agents which altered cyclic nucleotide levels on cell proliferation. Multiplication stimulating activity (MSA, 1 microgram/ml), a member of the somatomedin family, stimulated cell proliferation after 48 hr. It had little effect on cellular cyclic nucleotide levels, measured by radioimmunoassay. Horse serum (HS) and fetal bovine serum (FBS) stimulated cell proliferation approximately equally. Neither affected cAMP levels; FBS reduced cGMP to 33% of control values, but HS had no effect. Thus, there was no simple correlation between mitogenic action and cyclic nucleotide levels at any time from 5 min to 24 hr after addition of a purified mitogen or serum. Furthermore, agents which caused substantial changes in cyclic nucleotide levels had no effect on cell proliferation. Prostaglandin E1 (5 microM) elevated cAMP 440% without affecting cGMP levels or cell growth. A potent phosphodiesterase inhibitor, 1-methyl-3-isobutylxanthine (MIX, 0.1 mM), when added alone or in the presence of MSA, HS, or FBS, elevated cAMP 200% and cGMP 167%, but it had little effect on their mitogenic action. Lastly, a purified mitogen such as MSA, unlike serum, must be present for extended periods of time in order to stimulate cell proliferation. This makes it unlikely that a trigger mechanism functions in initiating cell division. We conclude that neither cAMP nor cGMP appear to be second messengers for the mitogenic action of MSA or serum on muscle cells. PMID- 6253509 TI - Kirsten murine sarcoma virus transformed cell lines and a spontaneously transformed rat cell-line produce transforming factors. AB - We have examined culture fluids from a variety of Kirsten murine sarcoma virus (KiMSV) transformed rat and mouse cells for the presence of factors which induce normal Rat-1 cells to assume the transformed phenotype. All KiMSV transformants produced transforming factor (TF). Revertants of KiMSV transformed rat or mouse failed to release TF as did normal rat or mouse cells. Cells transformed by a temperature sensitive mutant of KiMSV produced TF at the permissive temperature but not at the nonpermissive temperature. Further, cells from a spontaneous transformant of Rat-1 cells also produced TF. TF is a small polypeptide which competes for the epidermal growth factor receptor. Its effect upon normal cells is reversible and requires de novo RNA and protein synthesis. Cells treated with TF lose the actin fibers observed in normal fibroblasts, assume a transformed cell morphology, become anchorage independent for growth, grow in low concentrations of serum, grow to a high cell density, and have an increased rate of hexose uptake. PMID- 6253510 TI - Temperature dependent expression of polyoma virus in murine embryonal carcinoma cells. AB - At 37 degrees C, undifferentiated murine teratocarcinoma cells (PCC4) are resistant to infection with SV40 and Polyoma virus. When infection is carried out at 31 degrees C, these cells become fully susceptible to a variety of polyoma virus strains, including wt, ts-a, and hr-t; they also display an increased susceptibility to polyoma virus mutants (PyE.C.) which have been selected for their ability to develop in PCC4 cells at 37 degrees C (Vasseur et al., '80). However, expression of SV40 is still restricted at 31 degrees C and no T antigen can be detected. PCC4 cells grown at 31 degrees C express the characteristic embryonal surface antigen(s), but no H2 antigen, and do not produce plasminogen activator. PyE.C. mutants and other polyoma virus strains cannot develop at 37 degrees C in nullipotent F9 embryonal carcinoma cells and restriction is not abolished at 31 degrees C. The results indicate that: i) Resistance of PCC4 cells to polyoma virus and to SV40 are not mediated by the same process; ii) loss of restriction of polyoma in PCC4 cells does not require cell differentiation; iii) F9 and PCC4 cells control polyoma virus expression through different mechanisms. PMID- 6253511 TI - Lymphocyte capping induced by polycationized ferritin. AB - In order to better understand the mechanism of lymphocyte surface receptor redistribution induced by externally added ligands, polycationized ferritin (PCF), a nonconventional ligand, was tested using both fluorescence and electron microscopy for its ability to cause patching and capping of anionic molecules on the surface of both transformed and normal mouse lymphocytes. Binding of PCF at 0 degree C for 1 hour induces the appearance of patches; subsequent incubation at 37 degrees for 30--60 minutes causes the formation of a cap structure with the lymphoid cells tested (T-lymphoma cells and splenic lymphocytes). Using various experimental treatments (e.g., sodium azide, cytochalasin B and D, colchicine, prefixation, and cold temperatures), PCF-induced capping has been found to be temperature sensitive, and to require metabolic energy and an intact cytoskeletal system. In addition, using double immunofluorescence techniques which involve rhodamine-labeled PCF and fluorescein-conjugated heavy meromyosin, it has been observed that the formation of the PCF-induced cap coincides with an accumulation of intracellular actin directly beneath the cap structure. Furthermore, agents such as dibutyryl cyclic AMP and theophylline, which cause an increase in intracellular cyclic AMP, have been shown to stimulate PCF-associated capping. This study suggests that increasing levels of intracellular cyclic AMP may activate, directly or indirectly, membrane-associated contractile elements required for the aggregation of membrane proteins into patches and caps. PMID- 6253512 TI - On the chemistry of beta-lactamase inhibition by 6 beta-bromopenicillanic acid. PMID- 6253513 TI - Nitrosation and nitrosylation of haemoproteins and related compounds. Part 4. Pentaco-ordinate nitrosylprotohaem as the pigment of cooked cured meat. Direct evidence from E.S.R. spectroscopy. PMID- 6253514 TI - [A comparative study of "slowly resorbed suture material" in the rat with tracheal sutures (author's transl)]. AB - The authors studied the outcome of polyglycotic acid and braided polyglactine suture material used on the trachea of the rat. The compared them with two non self-resorbing sutures. 61 rats were operated. The study was on the resistance of the slowly resorbing material over time, as well a macroscopic and histological observations and the tolerance of the 4 materials tested. The merit of this work is to show that these slowly absorbed materials are far from the ideal solution for sutures of the tracheo-bronchial tree and that single-ply nylon suture has remarkable tissue tolerance. PMID- 6253515 TI - Comparison of seven enzyme immunoassay systems for measurement of cytomegalovirus. AB - The relative sensitivities of seven different enzyme immunoassay (EIA) systems for the measurement of cytomegalovirus (CMV) were compared. Methods which used two separate antisera to CMV provided the greatest degree of sensitivity. Equivalent sensitivity was noted with the use of either enzyme-labeled antiglobulin or unlabeled staphylococcal protein A and rabbit enzyme-antienzyme complex to measure the second anti-CMV antibody bound to the solid phase. Single antibody methods were less sensitive than the double-antibody methods but were more sensitive than an inhibition EIA. However, the sensitivity of the inhibition EIA was improved when CMV-antibody complexes were separated from unreacted antibody by means of precipitation with polyethylene glycol. Double-antibody EIA systems are preferable when antisera prepared in two different animal species are obtainable. However, a number of single-antibody EIA systems can be formulated for use in situations where only a single antiserum is available. PMID- 6253516 TI - Four-layer radioimmunoassay for detection of adenovirus in stool. AB - A four-layer antispecies radioimmunoassay (RIA) was developed for the detection of adenovirus in stool specimens. Polystyrene beads were used as the solid phase, anti-adenovirus guinea pig immunoglobulin (1 microgram per bead) was used as the primary antibody, anti-adenovirus rabbit immunoglobulin (16 micrograms/ml) was used as the secondary antibody, and 125I-labeled sheep anti-rabbit immunoglobulin was used as the indicator antibody. A highly purified, crystallized adenovirus type 2 hexon antigen was used as the immunizing antigen for the production of hyperimmune sera. The sensitivity of the test was 1 ng of hexon protein per ml. Each of the 13 stool specimens positive for adenovirus by electron microscopy was positive for adenovirus by the RIA. Of 200 nonconcentrated stool specimens negative by electron microscopy, 14 additional specimens were positive by the RIA, increasing the detection rate from 6% by electron microscopy to 13% by the RIA. A confirmatory test was done on the RIA-positive, electron microscopy negative specimens, and the test indicated a true specific result with each specimen. A confirmatory test was also done on each specimen with a low positive counts per minute value. The specificity of the RIA was further demonstrated by the fact that a positive result was found with only 3 of 295 specimens positive by the rotavirus RIA. In two of these three specimens, adenovirus and rotavirus were also detected simultaneously by electron microscopy, and the third specimen was from a patient with serological evidence for a dual infection. The adenovirus and rotavirus RIAs are now in a routine diagnostic laboratory, and in the 307 stool specimens tested during the first 5 months, the positive rate was 32% for rotavirus and 9.5% for adenovirus. PMID- 6253517 TI - Cryopreservation of virus-infected cells for use in the fluorescent antibody to membrane antigen test. AB - Tissue culture cells infected with varicella-zoster, respiratory syncytial, para influenza types 1, 2, and 3, and influenza A/Texas/1/77 and A/USSR/90/77 viruses were exposed to ultraviolet light and frozen in the presence of a final concentration of 20% glycerol. These cells were quick thawed at 37 degrees C and compared with freshly prepared, living infected tissue culture cells in assays of fluorescence antibodies to membrane antigens of the infecting agents in serum, nasal wash secretions, colostrum, and breast milk. Frozen cells performed as efficiently as fresh cells as targets and retained their activity for long periods of time. Cryopreservation combined with photoinactivation of infected target cells allows this useful antibody test to be performed in routine serology laboratories. PMID- 6253518 TI - Coproantibodies in hepatitis A: detection by enzyme-linked immunosorbent assay and immune electron microscopy. AB - A collection of 104-fecal specimens from 45 patients with hepatitis A, 14 patients with hepatitis B, 10 patients with non-A, non-B hepatitis, 6 patients with diseases other than hepatitis, and 18 healthy adults were studied for the presence of secretory immunoglobulin A and immunoglobulin M to hepatitis A virus by solid-phase enzyme-linked immunosorbent assay and immune electron microsopy. Specific fecal antibody was found only in patients with hepatitis A. Of 54 specimens from patients with hepatitis A, only 10 (18.5%) possessed detectable levels of fecal antibody, and each of these was collected within 10 days from the onset of dark urine. All 10 fecal specimens contained hepatitis A-specific secretory immunoglobulin A, and 4 were also positive for hepatitis A-specific immunoblobulin M. Four of the 10 antibody-positive specimens also contained hepatitis A virus particles which could be shown by immune electron microscopy to be coated with specific secretory immunoglobulin A. Since specific fecal antibody was not detected in all the patients with hepatitis A that were studied, it would appear to have limited diagnostic value, although its detection is evidence of recent infection. PMID- 6253519 TI - Immunofluorescence technique for detection of human cytomegalovirus (HCMV) antibodies against HCMV-induced late antigens with elimination of immunoglobulin G-receptor staining. AB - An immunofluorescence technique is described which permits the elimination of nonspecific cytoplasmic staining from late antigen preparations by using in situ a buffer containing Nonidet P-40. PMID- 6253520 TI - Evaluation of a role for 1,25-dihydroxyvitamin D3 in the pathogenesis and treatment of X-linked hypophosphatemic rickets and osteomalacia. AB - Although a defect in renal transport of phosphate seems well established as the primary abnormality underlying the pathogenesis of X-linked hypophosphatemic rickets and osteomalacia, several observations indicate that renal phosphate wasting and hypophosphatemia cannot solely account for the spectrum of abnormalities characteristic of this disease. Thus, in the present study, we investigated the potential role of abnormal vitamin D metabolism in the pathogenesis of this disorder and the effect of 1,25-dihydroxyvitamin D(3) therapy on both the biochemical abnormalities characteristic of this disease and the osteomalacia. Four untreated patients, ages 14-30 yr, had normocalcemia (9.22+/-0.06 mg/dl); hypophosphatemia (2.25+/-0.11 mg/dl); a decreased renal tubular maximum for the reabsorption of phosphate per liter of glomerular filtrate (2.12+/-0.09 mg/dl); normal serum immunoreactive parathyroid hormone concentration; negative phosphate balance; and bone biopsy evidence of osteomalacia. The serum 25-hydroxyvitamin D(3) concentration was 33.9+/-7.2 ng/ml and, despite hypophosphatemia, the serum level of 1,25-dihydroxyvitamin D(3) was not increased, but was normal at 30.3+/-2.8 pg/ml. These data suggested that abnormal homeostasis of vitamin D metabolism might be a second defect central to the phenotypic expression of X-linked hypophosphatemic rickets/osteomalacia. This hypothesis was supported by evaluation of the long-term response to pharmacological amounts of 1,25-dihydroxyvitamin D(3) therapy in three subjects. The treatment regimen resulted in elevation of the serum 1,25-dihydroxyvitamin D levels to values in the supraphysiological range. Moreover, the serum phosphate and renal tubular maximum for the reabsorption of phosphate per liter of glomerular filtrate increased towards normal whereas the phosphate balance became markedly positive. Most importantly, however, repeat bone biopsies revealed that therapy had positively affected the osteomalacic component of the disease, resulting in normalization of the mineralization front activity. Indeed, a central role for 1,25-dihydroxyvitamin D(3) in the mineralization of the osteomalacic bone is suggested by the linear relationship between the serum level of this active vitamin D metabolite and the mineralization front activity. We, therefore, suggest that a relative deficiency of 1,25-dihydroxyvitamin D(3) is a factor in the pathogenesis of X-linked hypophosphatemic rickets and osteomalacia and may modulate the phenotypic expression of this disease. PMID- 6253521 TI - Beta-adrenergic receptors and isoproterenol-stimulated potassium transport in erythrocytes from normal and hypothyroid turkeys. Quantitative relation between receptor occupancy and physiologic responsiveness. AB - We have previously reported that in hypothyroid turkeys the number of beta adrenergic receptors in intact erythrocytes is reduced by approximately 50% without any changes in the affinity of the receptor for the agonist, isoproterenol. In view of the physiological action of the catecholamines to stimulate bidirectional ion fluxes in these cells, we have now examined the possibility that the decrease in beta receptor number might be associated with concomitant changes in catecholamine-dependent potassium ion transport. Hypothyroid turkey erythrocytes display decreased sensitivity to isoproterenol stimulated potassium influx. Half-maximal stimulation of potassium influx occurs at 9.2+/-1.7 nM in hypothyroid cells as opposed to only 3.8+/-0.4 nM in normal cells (P < 0.005). A maximal stimulatory concentration of isoproterenol (100 nM) leads to the same increment in ion flux in erythrocytes from hypothyroid and normal turkeys. Analysis of the quantitative relationship between isoproterenol concentration, receptor occupancy, and associated effects upon potassium influx shows that at low levels of isoproterenol, where occupancy is linear with agonist concentration, occupation of a given number of beta receptors leads to a stimulation of potassium transport that is identical in erythrocytes from normal and hypothyroid turkeys. Thus, decreased sensitivity to catecholamine-stimulated potassium transport in hypothyroidism can be attributed to the decrease in receptor number and the resulting two- to threefold higher isoproterenol concentration required for occupancy of the same number of beta receptors. Once a single receptor is occupied, however, the more distal components of the sequence of events mediating the physiological response to beta-adrenergic agonists in the hypothyroid cell function as they do under normal circumstances. It would appear, therefore, that the decrease in sensitivity to isoproterenol-dependent ion flux in the hypothyroid turkey erythrocyte can be accounted for solely by the decrease in receptor number. These changes are shown to occur in the absence of any modifications in the number of Na(+)-K(+) ATPase effector units per cell. PMID- 6253523 TI - Transferrin binding to peripheral blood lymphocytes activated by phytohemagglutinin involves a specific receptor. Ligand interaction. AB - Immunohistological studies have indicated that membrane sites binding transferrin are present upon activated human peripheral blood lymphocytes. In this study, we have investigated transferrin uptake in human lymphocytes exposed to phytohemagglutinin (PHA), by quantitative radiobinding and immunofluorescence in parallel. In stimulated lymphocytes, binding was maximal after a 30-min incubation, being greatest at 37 degrees C, and greater at 22 degrees C than at 4 degrees C. Although some shedding and endocytosis of transferrin occurred at 22 degrees and 37 degrees C, these factors, and resulting synthesis of new sites, did not affect measurement of binding which was found to be saturable, reversible, and specific for transferrin (K(a) 0.5-2.5 x 10(8) M(-1)). Binding was greater after a 48-h exposure to PHA than after 24 h, and was maximal at 66 h. Sequential Scatchard analysis revealed no significant elevation in affinity of interaction. However, although the total number of receptors increased, the proportion of cells in which binding of ligand was detected immunohistologically increased in parallel, and after appropriate correction, the cellular density of receptors remained relatively constant throughout (60,000-80,000 sites/cell). Increments in binding during the culture period were thus due predominantly to expansion of a population of cells bearing receptors. Similar differences in binding were apparent upon comparison of cells cultured in different doses of PHA, and in unstimulated cells binding was negligible. Transferrin receptors appear, therefore, to be readily detectable only upon lymphocytes that have been activated. PMID- 6253522 TI - Phorbol diester-induced macrophage differentiation of leukemic blasts from patients with human myelogenous leukemia. AB - Phorbol esters, including 12-O-tetradecanoylphorbol 13-acetate (TPA), induce terminal macrophagelike differentiation of cells from human acute myelogenous leukemia lines. We report that myelogenous leukemia cells obtained from patients undergo macrophagelike differentiation after exposure to TPA. The myeloid leukemic cell cultured with TPA became adherent to charged surfaces with long filamentous pseudopodia; developed positive staining for alpha-napthyl acetate esterase, increased lysozyme secretion, reduced nitroblue tetrazolium, and acquired the ability to phagocytose candida. Cells from patients with lymphocytic leukemia did not become macrophagelike when cultured with TPA. PMID- 6253524 TI - Virus-induced decrease of insulin receptors in cultured human cells. AB - Viral infections may produce abnormalities in carbohydrate metabolism in normal subjects and profound changes in glucose homeostasis in insulin-dependent diabetics. Using an in vitro radio-receptor assay with 125I-labeled insulin and human-amnion (WISH) cells, the effect of viral infections on insulin receptors was examined. Both herpes simplex virus and vesicular stomatitis virus produced a 50% decrease in insulin binding. There was no evidence that this decrease was due to degradation of insulin. On quantitative analysis, this decrease in binding was found to be the result of a decrease in receptor concentration with no change in receptor affinity. The decrease in receptors occurred between 4 and 12 h, at the time viral antigens were being inserted into the plasma membrane of infected cells. Because the t 1/2 of insulin receptors in uninfected cells was between 14 and 24 h, the decrease in insulin receptors cannot be explained solely by virus induced shut-off of macromolecular synthesis. Moreover, viruses such as encephalomyocarditis that do not insert new antigens into the plasma membrane, did not cause changes in the number of insulin receptors. The most likely explanation is that virus-induced changes in the plasma membrane altered or displaced insulin receptors. It is concluded that the insulin receptor assay is a sensitive and quantitative method for studying the effect of viral infections on cell membranes. These data also suggest that abnormalities in glucose metabolism associated with some viral infections may be due, in part, to changes in the concentration of insulin receptors. PMID- 6253525 TI - Lipoxygenation of arachidonic acid as a source of polymorphonuclear leukocyte chemotactic factors in synovial fluid and tissue in rheumatoid arthritis and spondyloarthritis. AB - The predominant lipoxygenase products of arachidonic acid were extracted and purified from synovial fluid and sonicates of synovial tissue of patients with rheumatoid arthritis (RA), spondyloarthritis (SA), or a noninflammatory arthropathy (NIA). The concentration of 5(S),12(R)-dihydroxy-6,8,10 (trans/trans/cis)-14-cis-eicosatetraenoic acid (leukotriene B4) in synovial fluid was elevated significantly in patients with RA and a positive latex test for rheumatoid factor (P < 0.05, n = 14) and in patients with SA (P < 0.05, n = 10), compared with that of subjects with NIA (n = 9). The content of 5(S)-hydroxy 6,8,11,14-eicosatetraenoic acid (5-HETE), but not of leukotriene B4, was elevated significantly in synovial tissue of seven patients with RA in comparison with that of four subjects with NIA (P < 0.05). A single intra-articular injection of corticosteroid significantly lowered the synovial fluid level of leukotriene B4 in six patients with RA. These data suggest an involvement of the potent chemotactic factors 5-HETE and leukotriene B4 in human inflammatory disease. PMID- 6253526 TI - Deficiency of protein C inhibitor in combined factor V/VIII deficiency disease. AB - Activated protein C is an anticoagulant plasma protease enzyme that inactivates Factors V and VIII in plasma. Normal plasma contains a protein that inhibits activated protein C and that is distinct from previously described plasma protease inhibitors. Protein C inhibitory activity is not detectable in plasmas from four unrelated patients with combined Factor V/VIII deficiency but is present in normal amounts in plasmas from patients with simple factor V deficiency or Factor VIII deficiency. It is suggested that the molecular basis for combined Factor V/VIII deficiency that exhibits simple autosomal recessive inheritance is a deficiency of protein C inhibitor. PMID- 6253527 TI - Damage to Candida albicans hyphae and pseudohyphae by the myeloperoxidase system and oxidative products of neutrophil metabolism in vitro. AB - In previous studies, we noted that Candida hyphae and pseudohyphae could be damaged and probably killed by neutrophils, primarily by oxygen-dependent nonphagocytic mechanisms. In extending these studies, amount of damage to hyphae again was measured by inhibition of [(14)C]cytosine uptake. Neutrophils from only one of four patients with chronic granulomatous disease damaged hyphae at all, and neutrophils from this single patient damaged hyphae far less efficiently than simultaneously tested neutrophils from normal control subjects. Neutrophils from neither of two subjects with hereditary myeloperoxidase deficiency damaged the hyphae. This confirmed the importance of oxidative mechanisms in general and myeloperoxidase-mediated systems in particular in damaging Candida hyphae. Several potentially fungicidal oxidative intermediates are produced by metabolic pathways of normal neutrophils, but their relative toxicity for Candida hyphae was previously unknown. To help determine this, cell-free in vitro systems were used to generate these potentially microbicidal products. Myeloperoxidase with hydrogen peroxide, iodide, and chloride resulted in 91.2% damage to hyphal inocula in 11 experiments. There was less damage when either chloride or iodide was omitted, and no damage when myeloperoxidase was omitted or inactivated by heating. Azide, cyanide, and catalase (but not heated catalase) inhibited the damage. Systems for generation of hydrogen peroxide could replace reagent hydrogen peroxide in the myeloperoxidase system. These included glucose oxidase, in the presence of glucose, and xanthine oxidase, in the presence of either hypoxanthine or acetaldehyde. In the presence of myeloperoxidase and a halide, the toxicity of the xanthine oxidase system was not inhibited by superoxide dismutase and, under some conditions, was marginally increased by this enzyme. This suggested that superoxide radical did not damage hyphae directly but served primarily as an intermediate in the production of hydrogen peroxide. The possible damage to hyphae by singlet oxygen was examined using photoactivation of rose bengal. This dye damaged hyphae in the presence of light and oxygen. The effect was almost completely inhibited by putative quenchers of singlet oxygen: histidine, tryptophan, and 1,4-diazobicyclo[2.2.2]octane. These agents also inhibited damage to hyphae by myeloperoxidase, halide, and either hydrogen peroxide or a peroxide source (xanthine oxidase plus acetaldehyde). Myeloperoxidase-mediated damage to hyphae was also inhibited by dimethyl sulfoxide, an antioxidant and scavenger of the hydroxyl radical. These data support the involvement of oxidative mechanisms and the myeloperoxidase-H(2)O(2) halide system, in particular in damaging hyphae in vitro and perhaps in vivo as well. PMID- 6253528 TI - Potential mediator of inflammation. Phagocyte-derived oxidants suppress the elastase-inhibitory capacity of alpha 1-proteinase inhibitor in vitro. AB - Human polymorphonuclear leukocytes, monocytes, or pulmonary alveolar macrophages, stimulated in vitro by phorbol myristate acetate (PMA), released reactive oxygen species able to suppress the elastase inhibitory capacity (EIC) of human serum. Immunoelectrophoresis using antibodies against alpha(1)-proteinase inhibitor (alpha(1)-Pi) and elastase showed that inactivation of alpha(1)-Pi was responsible for the decreased serum EIC. Treatment of phagocyte-inactivated serum with a reducing agent (dithiothreitol) resulted in significant recovery of EIC, suggesting that alpha(1)-Pi had been oxidatively inactivated. Serum EIC was partially protected by superoxide dismutase or catalase. Hydrogen peroxide alone had no effect on serum EIC. Thus, neither H(2)O(2) nor O(2) (-) alone, but a product of the two, may have oxidatively inactivated alpha(1)-Pi. In support of the foregoing, neutrophils or monocytes from a patient with chronic granulomatous disease failed to produce detectable levels of O(2) (-) after incubation with PMA. These cells also failed to suppress serum EIC. In the case of PMA-stimulated polymorphonuclear leukocytes or monocytes, extracellular myeloperoxidase may have also played a role in alpha(1)-Pi inactivation since serum EIC was partly protected by azide, cyanide, or the depletion of extracellular chloride. Indeed, in a cell-free system consisting of purified myeloperoxidase, a glucose oxidase H(2)O(2)-generating system, and Cl(-), the EIC of human serum or purified alpha(1)-Pi could also be suppressed. Omission of any single reactant prevented this effect, as did NaN(3) or catalase, suggesting that enzymatically active myeloperoxidase and H(2)O(2) were necessary. Immunoelectrophoresis of myeloperoxidase-inactivated serum showed that, as before, inactivation of alpha(1)-Pi was responsible for the decreased EIC. Treating myeloperoxidase inactivated serum with dithiothreitol led to significant recovery of EIC, again suggesting that oxidative inactivation of alpha(1)-Pi had occurred. Oxidative inactivation of alpha(1)-Pi in the microenvironment of inflammatory cells, at sites of acute or chronic inflammation, may allow proteases released from these cells to damage adjacent connective tissue components more readily. PMID- 6253529 TI - Paraproteinaemia in neurological disease: incidence, associations, and classification of monoclonal immunoglobulins. AB - Fifty-six patients presenting with neurological complaints were found to have paraproteinaemia unassociated with immunocytic malignancy; 16 patients presented with peripheral neuropathy. There was an association between IgM paraproteinaemia and an idiopathic neuropathy with markedly slowed nerve conduction velocities. PMID- 6253530 TI - Excretion of faecal viruses during the first year of life. AB - Four hundred faecal samples, collected at approximately weekly intervals during the first year of life from nine babies, were examined for the presence of viruses. Only nine (2.3%) samples contained a virus detectable by electron microscopy, and on all but one occasion only one type of virus was present and that in small numbers. Thirty (7.5%) of the specimens contained an enterovirus other than poliovirus, and these represetned 10 infections in four of the children. All three types of poliovirus, probably vaccine derived, were excreted by each child, and one or more types were present in 87 (21.8%) of the samples. There was no evidence to suggest that any of the illnesses suffered by the children had been caused by faecal viruses. Infection with these viruses was uncommon in the first three months of life but more than 40% of faecal samples obtained from children between the ages of 3 months and 1 year contained a faecal virus. PMID- 6253531 TI - Recognition of intraduct mammary carcinoma. PMID- 6253532 TI - Rotavirus infection. PMID- 6253533 TI - Postnatal development of GABA-ergic neurons in the rabbit retina. AB - Uptake, synthesis, storage, and release of gamma-aminobutyric acid (GABA) are some of the characteristic properties of GABA-ergic neurons. In the present study, we have used these properties as physiological probes to follow the emergence and maturation of GABA-ergic neurons during postnatal development of the rabbit retina. There is autoradiographic, immunocytochemical, and pharmacological evidence that some amacrine cells and certain neurons in the ganglion cell layer probably use GABA as the neurotransmitter. These neurons take up GABA, contain the GABA-synthesizing enzyme L-glutamic acid decarboxylase (GAD, EC 4.1.1.15), and release the accumulated GABA by a CA++-dependent mechanism when depolorized with high extracellular K+ concentration. In this study, we show that certain neurons in the newborn retina already possess a specific mechanism for GABA uptake. The positions and numbers of these cells in the developing retina suggest that they will become GABA-ergic neurons in the adult retina. These putative GABA-ergic neurons are, however, probably immature at birth because newborn retinas contain only low levels of GABA and GAD. Additionally, there is relatively little K+-stimulated, Ca++-dependent release of (3H)-GABA from the newborn retinas. GABA concentrations and GAD activities in developing retinas increase steadily postnatally, reaching about 80% of the adult levels by day 9. The activities of the GABA-degrading enzyme, GABA-glutamate transaminase (GABA-T, EC 2.6.1.19), follow a similar pattern of maturation during retinal development. K+ stimulated GABA release, however, remains low until about day 6, and then increases dramatically from 20% to 85% of the adult level over the next 3 days. Taken together, our results indicate that in the rabbit retina, the commitment by certain neurons to use GABA as the transmitter is made prenatally. These neurons are immature at birth but are biochemically, physiologically, and probably functionally mature by about 9 days after birth. PMID- 6253534 TI - Postnatal development of glycinergic neurons in the rabbit retina. AB - Certain neurons in the adult rabbit retina possess a high-affinity uptake mechanism for glycine and release it in response to elevated K+ concentrations in the medium. Although the evidence is not yet complete, these properties, together with pharmacological studies, suggest that the glycine-accumulating neurons may be a subpopulation of amacrine cells and may use glycine as a neurotransmitter. In the present study, we have used the uptake and K+-stimulated release of glycine as physiological probes to follow the emergence and maturation of putative glycinergic neurons during postnatal development of the rabbit retina. We show that certain neurons in the newborn retina already possess a specific high-affinity mechanism for glycine uptake. The positions and density of these cells in the developing retina suggest that they will become glycine-accumulating neurons of the adult retina. Thus, similar to our earlier study on the development of GABA-ergic neurons in this retina, the commitment by certain retinal neurons to be glycinergic, if indeed these cells use glycine as the transmitter, is made prenatally. These putative glycinergic neurons are, however, probably immature at birth, because they do not release the accumulated glycine in response to high K+ concentrations in the medium. In fact, there is practically no K+-stimulated release of preloaded glycine from the retina until about 7 days after birth, after which the release increases drastically to about 65% of the adult level on day 10 and 80% on day 12. Assuming that this release originates synaptically, our finding suggests that the putative glycinergic neurons may be functionally mature by 10-12 days after birth. Additionally, our results show that during development of the rabbit retina, the mechanism for high affinity glycine uptake emerges and matures much earlier than the mechanism for K+-stimulated glycine release. PMID- 6253536 TI - Excitation and inhibition of marginal layer and interstitial interneurons in cat nucleus caudalis by mechanical stimuli. AB - In cats anesthetized with urethane, the caudal medulla was stabilized in preparation for intracellular recording from interstitial neurons in the descending tract of the trigeminal nerve and from neurons in lamina I of nucleus caudalis. Glass micropipets (10-50 M ohms) were advanced from the surface to a maximum depth of 350 micrometer. When DC potential shifts occurred, it was found that mechanical stimuli to the face generated bursts of positive-going spikes, followed in some cases by inhibitory postsynaptic potentials (IPSPs). Subdermal electrical stimulation of the face in each receptive field almost always enabled the same neuron to be driven electrically. Recordings were classified as from primary afferent fibers or from interneurons. Primary fibers had a purely positive spike, with a latency varying by no more than 0.05 msec, and could follow stimulation at 500 Hz. The mean latency for the fibers was 1.87 +/- 0.06 msec (n=75), and their absolute refractory period was 0.42 +/- 0.02 msec (n=36). Recordings were classed as from interneurons if there was an IPSP or the latency was at least 4 msec, with a variation of latency of at lest 0.5 msec. Responses thought to be monosynaptically driven had a mean latency of 2.09 +/0 0.07 msec (n=32) and could follow pairs of stimuli at a mean minimum interval of 0.70 +/- 0.06 msec (n=20). Responses thought to be polysynaptically driven had a mean latency of 7.9 +/- 1.08 msec (n=49) and a mean interstimulus interval of 2.96 +/- 0.84 (n=20). Most responses were generated by brushing the face (n=87), some by pressure on the face (n=25), and a few by pinching the skin of the face (n=6). Interneuron responses were most commonly recorded in the first 200 micrometer of the descending tract, and this position was confirmed by the injection of pontamine sky blue and the examination of frozen sections. The recordings were thought to be from dendrites of marginal and interstitial cells or the somas of interstitial cells. The IPSPs which followed spike potentials could only follow stimuli at 10 Hz or less. The failure appeared to be at a primary afferent synapse upon an inhibitory interneuron. Collision tests between mechanically evoked and electrically evoked responses showed long-lasting inhibition of the response to electrical stimulation after collision. Presynaptic inhibition exerted on the primary afferent excitation was suggested as the explanation. PMID- 6253535 TI - Ordinal position and afferent input of neurons in monkey striate cortex. AB - From the extracellular recording of single units in the monkey striate cortex and electrical stimulation at two selected sites in the optic radiations it was possible to estimate 1) the ordinal position of striate neurons (i.e., whether they received a monosynaptic, disynaptic or polysynaptic input from the thalamus) and 2) the nature of the afferent input to these neurons (i.e., whether it came from the magnocellular or parvocellular subdivision of the lateral geniculate nucleus (LGN)). Based on receptive field properties six major classes of striate neuron were identified--three which lacked orientation specificity (the ON center, the OFF-center, and the ON/OFF or nonoriented (N-0) receptive fields) and three with orientation specific responses (the S, the C, and the B categories of receptive field). Units lacking orientation specificity were concentrated in laminae 4A, 4C beta and 6 while, for the cells with orientation specificity, C cells were found in laminae 4B and 6, B cells in 2/3 and 5, and S cells predominantly in laminae 2/3, 4C alpha, and 5. The results of electrical stimulation indicated that cell-to-cell transmission time in the monkey striate cortex is 1.5 msec, and latency measures showed that cells with a monosynaptic drive from the thalamus were confined to laminae 4 and 6 while disynaptically driven cells were found principally in upper lamina 4 (4A and 4B). No cell class was identified exclusively with a given ordinal position and there were many types of potential first-order neurons. The conduction time from one stimulating electrode to the next in the optic radiation was used to identify the afferent input to each striate neuron. The input to color-coded neurones was found to come exclusively from parvocellular layers while the C cells and two subclasses of the S cell (S2 and S3) were driven predominantly by the magnocellular subdivision. For other cell types (those with ON-center, N-0, and S1 receptive fields) the input came from either type of LGN neuron. The laminar distribution of neurons receiving a direct input from the magnocellular and parvocellular streams is in accord with the results of anatomical studies into the site of termination of the LGN input. The cell types receiving these direct inputs vary in the two streams so that the parvocellular input terminates on cells with ON-center and N-0 receptive fields in lamina 4C beta while the magnocellular input goes to cells with S, ON-center, N-0, and C receptive fields in lamina 4C alpha and the lower part of 4B. Consideration is given to the influence of these results on models for neural processing in monkey striate cortex and a comparison is drawn with the results of similar studies in the cat. PMID- 6253537 TI - Isolation of a pathogenic strain of ovine adenovirus type 5 and a comparison of its pathogenicity with that of another strain of the same serotype. PMID- 6253538 TI - Incomplete human adenovirus replication in canine tumour cells and serological evidence of infections in tumour-bearing canine pets. PMID- 6253539 TI - The response of three grouse species (Tetrao urogallus, Lagopus mutus, Lagopus lagopus) to louping-ill virus. PMID- 6253540 TI - Immunosuppression in toxoplasmosis: preliminary studies in mice infected with louping-ill virus. PMID- 6253541 TI - The effect of starch on forage fiber digestion kinetics in vitro. AB - Purified corn and wheat starch were added to alfalfa, Coastal bermudagrass, fescue, and orchardgrass hays at 0, 40, 60, and 80% of the total as-fed substrate, and fiber digestion kinetics were determined in vitro. Kinetics were estimated by the model R = Doe-k(t-L) + U where R is residue remaining at time t, Do is digestible fraction, k is digestion rate constant, L is discrete lag time, and U is indigestible fraction. Parameters of the model were estimated by logarithmic transformation and a direct nonlinear least squares procedure. Corn and wheat starch did not differ in their effect upon lag time of fiber digestion, digestion rate, or potential extent of digestion. Alfalfa had a shorter lag time of fiber digestion (.86 h) than Coastal bermudagrass (3.05 h), but not than orchardgrass or fescue (1.66 and 2.42 h). Orchardgrass differed in fiber digestion rate (.0542h-1) from Coastal bermudagrass (.0698h-1) but not from alfalfa or fescue (.0670 and .0658h-1). The potential extent of fiber digestion was similar for fescue (75.8%) and orchardgrass (76.0%). The potential extent of fibre digestion for alfalfa (50.9%) differed from Coastal bermudagrass (64.3%), and both of these forages differed from fescue or orchardgrass. Addition of starch resulted in a linear increase in lag time of fiber digestion, but digestion rate was not affected. Potential extent of digestion was decreased when starch was added. PMID- 6253542 TI - Relation between hormones and mammary gland function. PMID- 6253543 TI - Comparison of plasma histamine and cyclic nucleotides after antigen and methacholine inhalation in man. AB - Serial determinations of plasma histamine and cyclic nucleotides (adenosine monophosphate [AMP] and guanosine monophosphate [GMP]) were performed after inhalation of antigen and methacholine in four groups of subjects. In the first group, consisting of six antigen-sensitive subjects exhibiting bronchospasm after inhalation of ragweed or grass antigen, plasma histamine was elevated within 2 min and persisted for 30 min after inhalation of antigen. Peak histamine levels were between 18 to 80 ng/ml. In the second group, consisting of four nonatopic subjects, neither bronchospasm nor histamine was observed, despite inhalation of the same or 10-fold increased concentrations of antigen. In the third group, consisting of six subjects (three atopic and three nonatopic) exhibiting bronchospasm after inhalation of 2.5 to 10 mg of methacholine, sustained increases of histamine began at 1 min and persisted for 60 min after inhalation of methacholine. In the fourth group, seven subjects (two atopic, five nonatopic) without demonstrable bronchospasm despite inhalation of 2.5- to 10-fold increased doses of methacholine, no histamine was detected in the plasma at any time after inhalation of methacholine. Serial measurements of cyclic nucleotides showed no consistent changes in serum levels of cyclic AMP or cyclic GMP following inhalation challenge. We conclude that serum levels of histamine but not cyclic nucleotides change during bronchospasm induced by either antigen or methacholine. PMID- 6253544 TI - Health, laxation, and food habit influences on fiber intake of older women. AB - Fifty-nine elderly women interviewed about their food behavior, health, and laxation showed mean dietary fiber (DF) intakes of 14 gm. per day (range 3 to 34 gm. per day). DF intakes were lower for those in poor health and those with a tendency to constipation who took laxatives than for those who did not take laxatives or had no tendency to constipation. Factors not related to DF intake included age, participation in a meal program, living arrangements, understanding of fiber, and functional health. Cooked vegetables and bread added most to DF intakes. PMID- 6253545 TI - Thyroid hormone metabolism in patients with liver cirrhosis, as judged by urinary excretion of triiodothyronine. AB - This study included 35 patients with liver cirrhosis, 23 patients with hyperthyroidism, 12 with hypothyroidism, and 2 with other endocrine disorders. In the various endocrine disorders an appreciable amount of triiodothyronine (T3) was excreted into the urine but the daily excretion was fairly constant in each patient. Urinary excretion of T3 was negligible or depressed in hypothyroidism, but increased with a rise in the serum level of T3. Serum and urinary T3 decreased in liver cirrhosis, but the serum thyroxine (T4) level was within the normal range. When the cirrhosis patients were divided into 3 groups according to the urinary excretion of T3, a decrease of urinary T3 was associated with a decrease in the serum levels of T3 and free T3. An increase of serum thyroid stimulating hormone (TSH) either before or after injection of thyrotropin releasing hormone (TRH) was inversely correlated with a decrease of serum and urinary T3. The decrease of serum and urinary T3 was correlated with the magnitude of lh a decrease in the serum levels of T3 and free T3. An increase of serum thyroid-stimulating hormone (TSH) either before or after injection of thyrotropin-releasing hormone (TRH) was inversely correlated with a decrease of serum and urinary T3. The decrease of serum and urinary T3 was correlated with the magnitude of lh a decrease in the serum levels of T3 and free T3. An increase of serum thyroid-stimulating hormone (TSH) either before or after injection of thyrotropin-releasing hormone (TRH) was inversely correlated with a decrease of serum and urinary T3. The decrease of serum and urinary T3 was correlated with the magnitude of liver damage as judged by indocyanine green retention and a decreased urinary excretion of cyclic adenosine 3',5'-monophosphate. In vitro experiments indicated that rat liver, as compared to the kidney, heart and skeletal muscle, strongly converts T4 to T3, but this activity is greatly reduced by liver damage induced by ligation of the bile duct. It is suggested that patients with liver cirrhosis are, to some extent, in a state resembling subclinical hypothyroidism because of inability of the liver to metabolize a sufficient amount of T3 from T4. PMID- 6253546 TI - Hospital treatment of elderly neuropsychiatric patients. II. Statistical profile of the first 122 patients in a new teaching ward. AB - Data are presented on the first 122 patients admitted to a geropsychiatric teaching ward in a university hospital. A high incidence of medical problems are reflected by abnormal laboratory findings complicated the management of these patients, most of whom had dementia or depression. In all diagnostic categories, the patients appeared to benefit from the intensive inpatient treatment. Difficulties in the areas of diagnosis, treatment, length of hospital stay, discharge placement and program evaluation are discussed. PMID- 6253547 TI - Vasotonic angina--a review. PMID- 6253548 TI - Professional women's unanticipated contended feelings after the birth of a child. PMID- 6253549 TI - A novel approach to renal function: mechanism of diuretic action. PMID- 6253550 TI - A comparison of specialty choices among senior medical students using Bem Sex Role Inventory scale. PMID- 6253551 TI - Women and health care: a model for women's studies. PMID- 6253552 TI - Update on drug therapy: V. Liquid antacids. PMID- 6253553 TI - Women in medicine. PMID- 6253554 TI - Perioperative considerations for the hypertensive patient. PMID- 6253557 TI - Effects fo streptozotocin in the WDHA syndrome not amenable to radical surgery. AB - Two cases of Verner-MOrrison syndrome due to pancreatic carcinoma were treated H. h streptozotocin (STZ) according to the schedule suggested by the Division of Cancer Treatment of the National Cancer Institute. In both patients the drug caused a remission of the WDHA syndrome: therefore, this finding seems to recommend such treatment when the syndrome is not amenable to radical surgery. Renal toxicity is, however, an important limitation. It occurs mostly when STZ is administered by iv infusion. In one of the patients, after a serious impairment of renal function caused by STZ, prednisone controlled the syndrome for a long period of time. PMID- 6253555 TI - Short-term kinetics of serum adrenal steroids and plasma ACTH after a single dose of metyrapone in man. AB - The in vivo influence of metyrapone (M) on different adrenal enzymes has been studied by simultaneous measurement of serum progesterone (P), 17 hydroxyprogesterone (17-OHP), deoxycorticosterone (DOC), corticosterone (B), deoxycortisol (S), 18-hydroxydeoxycorticosterone (18-OHDOC), aldosterone and cortisol (F) as well as by the measurement of plasma ACTH before and after oral administration of 40 mg of M/kg at 08:15 in four healthy male subjects. The well known inhibitory effect of M on adrenal 11-hydroxylase is demonstrated by a decrease of serum F and B and synchronous increase of serum S and DOC after administration of M. The additional inhibition of 18-hydroxylase by M is documented by a decrease of serum 18-OHDOC in spite of a marked increase of serum DOC after M. The moderate increase of serum P and 17-OHP soon after drug administration, although plasma ACTH is highly elevated at this time, as well as the marked increase of these steroids in the afternoon synchronously to a rise of serum F and B suggest a further inhibitory effect of M on the enzyme prior to the total corticosteroid biosynthesis. This effect of M should be taken into account if ACTH activity is monitored in terms of adrenal steroid output in the metyrapone test. PMID- 6253556 TI - Differences in secretion characteristics in Cushing's disease with and without radiologically evident pituitary tumors. AB - In a group of 22 unselected patients with Cushing's disease 3 had a moderately enlarged pituitary fossa, while 6 patients showed asymmetry of the sella turcica at lateral tomography. This group of 9 patients with radiologically evident pituitary adenomas had:i) a higher average basal urinary excretion of 17 hydroxycorticosteroids which showed a greater day to day variation;ii) a greater (although insufficient) decrease of plasma cortisol in response to a single oral dose of 1 mg dexamethasone and larger postdexamethasone rebound excretion of urinary 17-hydroxycorticosteroids after 8 mg dexamethasone daily for two days; and iii) a larger maximal increase of plasma cortisol after lysine vasopressin administration than the other 13 patients. The increase in the size of a pituitary (micro-) adenoma in patients with Cushing's disease is accompanied by a more severe hypercortisolism and an increased responsiveness of the pituitary adrenal axis to the manipulations mentioned. PMID- 6253559 TI - Cytochemical localization of ouabain-sensitive (K+)-dependent p-nitrophenyl phosphatase (transport ATPase) in human blood platelets. AB - The ultrastructural cytochemical localization of a potassium-dependent oubain sensitive nitrophenyl phosphatase (transport ATPase) activity in human blood platelets is described. This potassium-dependent nitrophenyl phosphatase activity was not affected by 5 mM levamisole, indicating that the reaction product identified was not due to nonspecific alkaline phosphatase activity. The K+ dependent nitrophenyl phosphatase was strictly localized to the platelet plasma membrane, while the open canalicular system and dense tubular system were devoid of reaction product. In contrast, (Ca2+,Mg2+)-activated ATPase activity was predominantly localized in the open canalicular system and dense tubular system with very little cytochemical activity expressed at the plasma membrane. These data demonstrate a relative segregation of these enzymes into unique membrane compartments of the human platelet. Such data may be useful with regard to identification of purified membrane fractions from platelets and may be significant with regard to the understanding of the function(s) of the different membrane compartments of the human platelet. PMID- 6253560 TI - Anti-carbohydrate activity of T cell-reactive chicken anti-mouse immunoglobulin antibodies. AB - The specificity of chicken anti-mouse immunoglobulin F(ab')2 antibodies, which bind readily to T cells and have been claimed to detect immunoglobulin on T cells, was analyzed by indirect immunofluorescence. It ws found that only a minor proportion of the total antibody bound to T cells whereas the major fraction bound only to B cells. The T cell-reactive antibody cross-reacted with bovine IgG and therefore could be purified on this basis by affinity chromatography. T cell staining was inhibitable with nonimmunoglobulin glycoproteins as well as immunoglobulin, in contrast to staining with the B cell-specific antibody fraction, which was only inhibited by immunoglobulin. This suggested that the T cell staining was caused by anti-carbohydrate antibody. Inhibition of T cell staining was abolished by periodate oxidation of the inhibitors but not by proteolytic digestion. In addition, the antigenic determinant on the cell surface was not destroyed by autoclaving. Finally, antibody was absorbed on a mucin Sepharose column and anti-T cell activity was found in the bound but not the unbound fraction. These results strongly suggest that the only anti-T cell activity in the chicken antibody is anti-carbohydrate antibody. PMID- 6253561 TI - Appearance of receptors for Macaca speciosa red blood cells on human fibroblasts transformed by simian virus 40. AB - Receptors for monkey red blood cells (MRBC) that are expressed on subpopulations of human lymphoid cells are coded by genes linked to the major histocompatibility complex (MHC) region. Since malignant transformation of cells is associated with changes in structures coded by the MHC region, 10 cultured human melanoma and sarcoma cells and autologous SV40-transformed fibroblasts were tested for expression of MRBC receptors and compared with normal autologous fibroblasts. Only 2 of the tumor cell lines and normal fibroblasts from the same individual formed rosettes with MRBC. On the other hand, SV40 transformation induced in all the fibroblasts expression of receptors for MRBC. MRBC receptors on SV40 transformed fibroblasts show properties similar to those on B lymphoid cells. PMID- 6253562 TI - PGBX, a prostagandin derivative, mimics the action of the calcium ionophore A23187 on human neutrophils. AB - The interactions have been studied of a water-soluble, polymeric derivative of prostaglandin B1, PGBX, with human polymorphonuclear leukocytes (PMN). PGBX, which is a potent ionophore of divalent cations, provoked superoxide anion (O2.-) generation and lysosomal enzyme release in cytochalasin B-treated PMN in the presence of extracellular divalent cations (Ca2+, Sr2+, Mg2+, Mn2+, Ba2+). Kinetic and dose-response studies showed that PGBX mimicked te action of ionophore A23187 in PMN. Both ionophores induced superoxide generation and release of enzymes from specific and azurophil granules (lysozyme > beta glucuronidase) without provoking release of the cytoplasmic marker enzyme lactic dehydrogenase. In contrast, the precursor of PGBX, prostaglandin B1 (PGB1), and arachidonate did not mimic ionophore-induced stimulation of PMN. PGBX induced enzyme release both in the presence of extracellular Ca2+ and Ba2+ (both of which it translocates in model liposomes), whereas A23187 showed specificity for Ca2+ (which it translocates preferentially over Ba2+). These studies indicate that the actions of a water-soluble polymer (PGBX) derived from a naturally occurring prostaglandin (PGB1) on human neutrophils resemble those of a classical ionophore (A23187). Moreover, they provide additional evidence that increments in the intracellular levels of divalent cations may signal stimulus-secretion coupling in human neutrophils. PMID- 6253563 TI - Analysis of the colloid osmotic step of complement-mediated immune hemolysis. PMID- 6253558 TI - Biochemistry of thyroid regulation under normal and abnormal conditions. AB - Perhaps in an oversimplified view, abnormal thyroid growth can be classified into two main categories: a) those cases due to excess of thyroid stimulators extrinsic to the gland; b) situations in which an intrinsic alteration in the gland occurs: Extrinsic (excess thyroid stimulation) Iodide deficiency with elevated TSH Goitrogens Graves' immunoglobulins Thyroid stimulating factors produced by tumors Dishormonogenesis with hypothyroidism Intrinsic (normal TSH) Increased sensitivity to TSH (iodine depletion) Altered autoregulation (?) Abnormal TSH receptor Other biochemical abnormalities From the studies performed in animals it can be concluded that since goiter appears before a detectable increase in serum TSH occurs, an intrinsic alteration in the thyroid gland would be responsible for the onset of growth. Under these conditions TSH would play a permissive role in promoting and maintaining the gland enlargement. In some aspects this situation is similar to that of certain endemic goiter areas. It may be postulated that under a mild iodine deficiency a decrease in thyroidal iodine concentration occurs (and/or in certain iodocompounds), thus rendering the gland more sensitive to the stimulatory action of TSH, and leading to the appearance of goiter. If this mechanism is able to maintain an euthyroid status no further alterations will occur. In more severely iodine deficient areas, or when additional factors such as dietary goitrogens are present, hypothyroidism develops and TSH is clearly elevated. A similar localized mechanism can be postulated for the development of nodular goiter. It is more difficult to explain the pathogenesis of goiter and tumors in nonendemic areas, since the biochemical findings so far reported are not conclusive. It seems likely that an alteration of the TSH receptor is a common factor to many tumors in man and animals. However, some contradictory results would preclude us from making a general statement. The wide variety of biochemical alterations reported would perhaps indicate, that there is not a single cause for the rise of abnormal thyroid growth and that different factors may play a role in the regulation of growth under such circumstances. It is to be hoped that future studies will provide a better comprehension of this problem. PMID- 6253564 TI - Identification of target antigen for antibody-dependent cellular cytotoxicity on cells carrying Epstein-Barr virus genome. AB - The target antigen for antibody-dependent-cellular cytotoxicity (ADCC) on Epstein Barr virus-(EBV) carrying lymphoblastoid cells expressing EBV-specific membrane antigen (MA) were examined with human serum antibody and adult human peripheral lymphocytes as effector cells. These studies confirmed that anti-MA-positive but not MA-negative sera were reactive in the ADCC. The ADCC reaction was positive with cells in which the MA consisted of late (LMA) and early (EMA) components. These included 1) MA-positive cells prepared by EBV antigen-adsorption, 2) cells carrying de novo-synthesized MA without adsorbed MA, and 3) EBV-producer cells expressing MA spontaneously. In all these preparations, the target cells were lysed roughly in parallel with the frequency of MA-positive cells. Inhibition of LMA synthesis in EBV-superinfected cells by phosphonoacetate (PA) reduced ADCC sensitivity significantly and to a far greater extent than MA synthesis as measured by immunofluorescence. This suggests that a target for ADCC is the PA sensitive LMA. No ADCC reaction occurred with the cell preparation comprised of a high percentage of MA-positive cells induced by 5-iodo-2'-deoxyuridine, which is believed to be EMA only. These results strongly suggest that the target antigen for ADCC in EBV-positive cells is a late MA but not early MA. PMID- 6253565 TI - Activation of C3H/HeJ macrophages by endotoxin. PMID- 6253567 TI - Circulating immune complexes associated with naturally occurring lymphosarcoma in pet cats. AB - Cats were classified into 4 categories by immunofluorescence antibody assay for the presence of feline leukemia virus (FeLV) and histologically as a) normal, FeLV-, b) normal, FeLV+, c) lymphosarcoma (LSA), FeLV+, and d) LSA, FeLV-. Determinations by Raji cell radioimmunoassay modified for cat serum revealed circulating immune complex (CIC) levels of healthy cats to be less than or equal to 50 micrograms equivalent aggregated cat immunoglobulin/ml (microgram/ml). In contrast, sera of cats in groups b, c, and d all contained significantly higher CIC levels (up to 12,000 micrograms/ml) associated with marked hypocomplementemia and C activation occurring via the classical pathway. Sera from FeLV+, LSA+ cats with high levels of CIC and sera of healthy cats were fractionated according to size and bouyant density by centrifugation through 10 to 40% sucrose gradients. Analysis of fractions from LSA+, FeLV+ sera revealed that both immune complexes (ICs), FeLV reverse transcriptase (RT), and IgG were present in fractions corresponding to a bouyant density of 1.15 to 1.18 g/ml. The CIC containing fractions activated C by the classical pathway. Sera from normal cats did not have CIC or RT and none of the fractions activated the classical pathway. These data suggest that vital antigen-antibody complexes are present in sera of viremic cats with LSA and these complexes activate the C system. PMID- 6253566 TI - The role of agonists that activate adenylate cyclase in the control of cAMP metabolism and enzyme release by human polymorphonuclear leukocytes. AB - An inverse relationship between cAMP content and effector function is ascribed generally to immune and inflammatory cells. Previous reports imply, however, that human polymorphonuclear leukocytes (PMN) are less responsive than other inflammatory cells to adenylate cyclase (AC) agonists. We therefore examined the effects of isoproterenol, prostaglandin E1 (PGE1), adenosine, and histamine on the adenosine 3',5'-monophosphate (cAMP) content of PMN and on particle stimulated lysosomal enzyme release. For comparison, the effect of AC agonists on the cAMP content of human peripheral lymphocytes was evaluated in parallel. Although potent stimuli for cAMP accumulation in lymphocytes, the AC agonists produced only marginal increases in the cAMP content of PMN; this difference in responsiveness was independent of agonist concentration or length of incubation. Inhibition of lysosomal enzyme release by the AC agonists was likewise marginal (< 20%). The addition of theophylline with isoproterenol produced additive inhibition without significant cAMP increases. Hydrocortisone, which caused a small increase in the cAMP content, markedly potentiated the effects of AC agonists on the cAMP level in PMN; the synergistic increases in cAMP were accompanied by additive effects on lysosomal enzyme release. It is concluded that human lymphocytes and PMN exhibit differential sensitivity to AC agonists and that this difference may provide a basis for the selective modulation of individual PMN- or lymphocyte-mediated events. PMID- 6253568 TI - Alteration of T and null lymphocyte frequencies in the peripheral blood of human opiate addicts: in vivo evidence for opiate receptor sites on T lymphocytes. AB - Street opiate addiction produces a significant depression in the absolute number of total T lymphocytes in peripheral blood as measured by the ability of the lymphocytes to rosette sheep red blood cells (SRBC). Associated with the decrease in T cells, there is an increase in the absolute number of null lymphocytes but no significant changes in B lymphocytes or total white blood cell count. The T cell values for 2 different populations of addicts (n = 12 and 32) are 31.8% and 23.1%, whereas the null cell values are 51.1% and 57.6%, respectively. The values for comparable control populations (n = 18 and 10) are: T% = 70.7% and 67.4%, and null % = 9.2% and 14.5%. Self-reported use of marihuana does not significantly alter the distribution of cell populations. A 1- to 3-hr incubation of addicted derived lymphocytes with 10(-6) to 10(-7) M Naloxone reverses both T cell depression and null cell increase by allowing the null cells to express SRBC receptors. Cyclic AMP and dibutyryl cyclic AMP can also convert the null cells to T cells. The conversion of null to T lymphocytes has additionally been measured by monitoring the increase in PHA-stimulated growth in 72-hr cultures as determined by tritiated thymidine incorporation into DNA. These results support the hypothesis that opiates can alter T lymphocyte number and function in vivo, and that this alteration may produce a significant degeneration in the immune competence of street opiate addicts. PMID- 6253569 TI - Functional properties of Ly 11.2 lymphocytes: a role for these cells in leukemia? AB - Functional studies of lymphocyte subpopulations reveal that Ly 11.2, a newly defined T cell surface antigen, is present on prothymocytes and natural killer cells, but not on suppressor T cells for antigen-specific IgE antibody responses, Ly 1+, 2-, 3- helper T cells nor on tumor-specific cytotoxic effector cells. Changes in the expression of Ly 11.2 regularly accompany leukemogenesis and are quite distinct from changes of other cell surface antigens thus far observed. After intrathymic inoculation of radiation leukemia virus (RadLV), many more Ly 11.2-positive cells are found expressing viral antigens than cells expressing other cell surface phenotypes. In addition, after RadLV inoculation, significantly more Ly 11.2-positive cells can be found in the thymus of susceptible mice than in the thymus of resistant mice. The greater availability of permissive (Ly 11.2-positive) cells in susceptible vs resistant hosts at the time when infectious virus is present may account for the shorter latency period and high leukemia incidence of susceptible vs resistant mice. PMID- 6253570 TI - Lectin-dependent neutrophil-mediated cytotoxicity against chicken erythrocytes: a model of non-myeloperoxidase-mediated oxygen-dependent killing by human neutrophils. PMID- 6253571 TI - Production and release of platelet-activating factor (PAF); dissociation from degranulation and superoxide production in the human neutrophil. AB - The generation of human PAF was examined using purified neutrophils from normal and CGD donors. PAF release occurred in response to all of the neutrophil stimuli examined, including PMA and the calcium ionophore A23187, which initiate the relatively selective release of specific granule constituents. PAF release was dissociable from neutrophil degranulation by 1) the lack of correlation between PAF titers and extent of enzyme release for different stimuli, 2) the strict dependence of PAF release on the presence of extracellular Ca++, 3) the different kinetics for release of PAF and granule enzymes, and 4) the ability of neutrophils significantly depleted of azurophil and specific granule constituents to release normal levels of PAF when stimulated with opsonized zymosan. PAF release was also normal, if not elevated, in neutrophils from patients with chronic granulomatous disease, demonstrating that the formation and release of PAF does not depend upon an intact superoxide generating pathway. PMID- 6253572 TI - The use of 125I-labelled protein A for the detection of humoral immunity to gross murine leukaemia virus. AB - A solid-phase radioimmunoassay utilising bind of 125I-labelled protein A to antibodies bound to virus adsorbed onto microtitre plates was shown to be suitable for detection of humoral immunity to Gross murine leukaemia virus (MuLV). The specificity of the reaction was shown by the fact that only homologous or closely related viruses effectively inhibited binding of antibodies to adsorbed virus. With this method a low level of spontaneous humoral immunity was demonstrated in sera from AKR/Crc mice, a strain with high concentrations of endogenous virus, whereas little or no anti-viral activity was found inCBA/H T6Crc, a subline that does not appear to express MuLV. PMID- 6253573 TI - A potentially oncogenic human papillomavirus (HPV-5) found in two renal allograft recipients. AB - We have observed 2 immunosuppressed renal allograft recipients with skin lesions induced by human papillomavirus type 5 (HPV-5). One recipient had multiple pityriasis versicolor-like (PV-like) skin lesions on his arms and trunk, and multiple Bowenoid in-situ skin cancers. The other had 2 warty lesions on the back of her fingers. Structural antigens of human papillomavirus type 5 (HPV-5) were identified in benign lesions from both patients by immunofluorescence. The histologic and ultrastructural features observed in lesions from both patients were similar to those previously seen in HPV-5-induced lesions occurring in patients with the rare disease epidermodysplasia verruciformis (EV). The severe form of EV is characterized by HPV-5-induced PV-like lesions, multiple skin cancers, and usually depressed cell-mediated immunity. The picture seen in one of our renal allograft recipients recalls this severe form of EV. HPV-5, until now, has been found only in EV patients. The role of this potentially oncogenic virus in skin cancers which are known to occur with increased frequency in immunosuppressed renal allograft recipients must be determined. PMID- 6253575 TI - [Biochemical factors of the attack in exercise-induced asthma (author's transl)]. PMID- 6253576 TI - [A case of selective IgA deficiency with the elevation of the serum antibody titers to herpes simplex virus in association with bacterial meningitis (author's transl)]. PMID- 6253574 TI - Prolyl and lysyl hydroxylase activities of human skin fibroblasts: effect of donor age and ascorbate. AB - Prolyl and lysyl hydroxylase activities in cultures of human skin fibroblasts from fetal to 94-yr-old donors were measured. In contrast to earlier studies with whole skin, neither prolyl nor lysyl hydroxylase activity was found related to donor age. Prolyl hydroxylase activity increased 3- to 6-fold when cell extracts were incubated with ascorbate and other hydroxylation cofactors before assay. A similar increase in prolyl hydroxylase activity occurred when cells were incubated with ascorbate. Lysyl hydroxylase activity remained unaltered under these conditions. PMID- 6253578 TI - The interaction of platelets, tumor cells, and vascular subendothelium. PMID- 6253577 TI - Cyclic AMP concentrations in human peripheral blood lymphocytes. Changes in association with cell purification. AB - In studies over a several year period of cAMP in human peripheral blood lymphocytes, a wide range of concentrations has been from low values (1 to 5 pmole/10(7) cells) to high values (80 to 160). Evaluation of this variation indicated that between cell separation and completion of the experiment, there eas a progressive decrease in lymphocyte cAMP as determined by RIA or immunocytochemistry. After a 2 hr incubation at 37 degrees C, a new steady state was reached at 5% to 30% of the initial concentration. This phenomenon was unique to lymphocytes and not preventable by manipulation of the incubation conditions. The cause of the cAMP reduction was shown to be decreasing AC activity. These data suggested the possibility that AC was activated during cell isolation. However, the phenomenon was present in cells not exposed to dextran or Ficoll Hypaque, and simulation of conditions employed during purification did not result in increased cAMP. Consequently, high-lymphocyte cAMP concentrations may be the normal levels in vivo. PMID- 6253579 TI - Fluorescence microphotometric studies of the transferrin receptor in human erythroid precursor cells. AB - The receptor site for transferrin in normal human erythroid precursor cells was studied by fluorescence microscopy. F-transferrin saturated with iron was used as probe of the available receptor sites on reticulocytes and nucleated red cells. In a series of experiments specificity and certain structural details of the ligand site were evaluated. Hydrolytic cleavage of exposed carbohydrate moieties by purified glycosidases revealed increased fluorescence after treatment of fixed cells by neuramindase, no perceptible change after N-acetylhexosaminidase treatment, but a pronounced decrease after exposure to beta-galactosidase. Inhibitor studies with monosaccharides and tryptic glycopeptides of normal reticulocytes complemented and amplified the results obtained with enzymes. The data suggest that an oligosaccharide chain is essential for specific transferrin binding to erythroid precursors. N-acetyl-neuraminic acid, galactose, N acetylgalactosamine, and fucose appear to be saccharides on the receptor. These studies also demonstrate the applicability of fluorescence microscopic methods to qualitative structural analysis of receptor biochemistry. PMID- 6253581 TI - Plasma requirement for the aggregation of rabbit platelets by an aggregating material derived from SV40-transformed 3T3 fibroblasts. AB - Certain tumors require platelets for metastases, and many of these aggregate platelets in vitro. We have studied their in vitro interaction by extracting a PAM from SV40-transformed 3T3 fibroblasts. The preparation is enriched with membrane vesicles and requires an intact sedimentable sialolipoprotein for activity. PAM aggregates platelets after a lag period (J Lab Clin Med 93:332, 1979) and requires plasma as a cofactor(s). Two plasma components have been identified with the use of PRP or GFP. The first component shortens the platelet aggregation lag period after preincubation of PAM with plasma at 37 degrees C for 10 min prior to its addition to PRP or GFP and is labile to heating at 56 degrees C for 30 min. However, the activated PAM (formed by incubation with plasma at 37 degrees C) is stable at 56 degrees C for 30 min. This labile factor appears to be a component(s) of the complement alternative pathway, since it is inactivated by treatment of plasma with cobra venom or zymosan; and guinea pig PRP deficient in C' 4 can be aggregated by PAM. The second component is a plasma factor that is stable to heating at 56 degrees C. Activated PAM can be sedimented at 100,000 x g. The sediment, when suspended in Veronal buffer, pH 7.4, does not aggregate GFP, however, addition of plasma heated at 56 degrees C restores the platelet aggregation response. Thus a material extracted from SV40 3T3 fibroblasts aggregates platelets in vitro in the presence of two factors: (1) a component(s) of the alternative complement pathway that activates PAM and shortens the platelet aggregation lag period and (2) a heat-stable factor that is required for activated PAM to aggregate platelets. PMID- 6253580 TI - Urinary cyclic 3',5'-adenosine monophosphate responses to exogenous and endogenous parathyroid hormone in familial benign hypercalcemia and primary hyperparathyroidism. AB - FBH is characterized by symptomless hypercalcemia, low urinary calcium excretion, normal iPTH values, generally normal parathyroid histology, and failure of subtotal parathyroidectomy is normalize serum calcium. We studies six patients with FBH from three kindreds, six patients with sporadic 1 omicron HPT, and six healthy volunteers. To characterize the renal response to PTH, 14 of the subjects had infusions of bovine PTE (300 U intravenously over 15 min) and, separately, stimulation of endogenous PTH release by infusion of disodium EDTA (50 mg/kg over 2 hr). PTE induced striking increases of UcAMP (nM/100 ml of GF) that were indistinguishable between controls and subjects having FBH. However, the rise of UcAMP in 1 omicron HPT was significantly reduced (p < 0.001) compared to controls or the FBH group. EDTA-induced hypocalcemia raised serum iPTH and UcAMP in all three groups; the increases of iPTH (two assays of differing specificity) were greatest in 1 omicron HPT and least in FBH. In contrast, increases of UcAMP were greatest in FBH and 1 omicron HPT and indistinguishable from one another. The increase of UcAMP considered as a function of the increase in PTH showed significantly greater UcAMP responses in FBH than in the other groups. These results are consistent with primary or secondary alterations of renal responsiveness to PTH in both FBH and 1 omicron HPT, which may in part explain the different renal tubular calcium handling in the two conditions. PMID- 6253582 TI - Congential granular cell myoblastoma. PMID- 6253583 TI - Correlation of cyclic AMP and cyclic GMP accumulation and steroidogenesis during stimulation of bovine luteal cells with luteinizing hormone. AB - The relationship between LH-induced steroidogenesis and the production of cyclic AMP and cyclic GMP was studied as a function of LH dose and time in isolated luteal cells from pregnant cows. Submaximal steroidogenic concentrations of LH caused a transient but significant rise in cyclic AMP that peaked after incubation for 5 min. A consequent rise in progesterone occurred at 30 min even though cyclic AMP had returned to the basal level at that time. Higher steroidogenic doses of LH elicited a maximum increase of cyclic AMP at 5 min and this was sustained for up to 1 h; the related progesterone production was significantly raised at 15 min and reached a maximum plateau at 30 min. The corresponding levels of cyclic GMP did not appear to be altered by any of the LH concentrations used. The present study has provided direct evidence that even at very low doses of LH, cyclic AMP plays an intermediary role in the stimulation of steroidogenesis in a mixed population of cells isolated from the bovine corpus luteum. Cyclic GMP, on the other hand, did not appear to play a role in the action of LH on the same population of luteal cells. PMID- 6253584 TI - Increase in the response to adrenocorticotrophin of isolated maternal adrenal cells from sheep in late pregnancy. AB - Adrenal cells were prepared from non-pregnant (anoestrous) sheep, from ewes at days 50, 100 and 130 of pregnancy and at term, and from animals at 1-5 days post partum. The ability of the cells to respond to adrenocorticotrophin (ACTH1-24), alpha-melanocyte-stimulating hormone (alpha-MSH), or combinations of these peptides has been examined in vitro. There was a progressive rise in the basal output of cortisol during pregnancy and in the absence of adrenocorticotrophin the cortisol output from adrenal cells of late pregnant and post-partum sheep the amount of ACTH required to produce half the maximum output of steroid (ED50) was 8 pg/ml. The ED50 increased in early pregnancy to 112 pg/ml and then fell to < 5 pg/ml between day 100 and term. At term both the stimulation ratio and the absolute increment in cortisol output elicited by a maximal concentration of ACTH were greater than at any other time tested in pregnant or non-pregnant sheep. Cortisol output during pregnancy was not increased by alpha-MSH, although at term the stimulatory effect of ACTH1-24 was partially antagonized by alpha-MSH. These results suggest that there may be an increase in the responsiveness of the maternal adrenal during pregnancy, although the factor(s) responsible remains unknown. PMID- 6253585 TI - Distribution of adrenocorticotrophic and lipotrophic peptides in the rat. AB - Intermediate and anterior lobes from the pituitary glands of female Wistar rats were freshly dissected and chromatographed on Sephedex G-50 and BioGel P6. Fractions were monitored with radioimmunoassays for NH2- and CO2H-terminal adrenocorticotrophin (ACTH), alpha-melanocyte-stimulating hormone (alpha-MSH), and alpha- and beta-endorphin. A large molecular weight, glycosylated form of corticotrophin-like intermediate lobe peptide (CLIP) which we have termed big CLIP, and a beta-MSH-like molecule were identified in the pars intermedia and in both lobes, a major peak of activity with the elution characteristics and cross reactivity of gamma-lipotrophic hormone (gamma-LPH) was detected. In the pars distalis, the larger peptides 1-39 ACTH and beta-LPH predominated, whereas in the pars intermedia, the smaller peptides alpha-MSH, CLIP, beta- and alpha-endorphin were more abundant. Chromatography of rat plasma revealed peaks of immunoreactivity in the corresponding positions to those detected in the pituitary gland. PMID- 6253586 TI - Effect of catechol oestrogens on induced ovulation in the immature rat. AB - The 'positive feedback' effect of exogenous oestradiol-17 beta in advancing ovulation induced by pregnant mare serum gonadotrophin (PMSG) has been used in the present study as a model in which to test the possible oestrogenic or antioestrogenic effects of the catechol oestrogens, 2-hydroxyoestradiol (2-OHE2) and 4-OHE2. Sprague-Dawley rats of 26 days of age were injected with 20 i.u. PMSG together with either vehicle alone or test steroids. The animals were killed 72 h later and the Fallopian tubes were examined for the presence of ova. Advancement of induced ovulation by treatment with oestradiol was confirmed; 2-OHE2, in doses of up to 100 micrograms, influenced neither the time of ovulation nor the number of ova present but 4-OHE2 was equipotent with oestradiol in doses varying from 0.5 micrograms (the minimum effective dose for both steroids) to 10 micrograms. The possible antioestrogenic effect of 2-OHE2 was tested by giving a 100 micrograms dose either at the same time or 2 h before PMSG plus 2 micrograms oestradiol or 4-OHE2. The effects of oestradiol and 4-OHE2 were not altered by this treatment. These data show that, in this model of 'positive feedback', 2 OHE2 has neither an oestrogenic nor an antioestrogenic action but that 4-OHE2 has a potent oestrogenic action, thus raising the question of a physiological role for 4-OHE2 in the regulation of ovulation. PMID- 6253587 TI - Effect of inhibition of converting enzyme on inactive renin in the circulation of salt-replete and salt-deplete normal subjects. AB - Angiotensin II exerts an inhibitory influence on active renin release from the kidney. To assess a possible role for angiotensin II in the release of inactive renin, levels in the circulation were measured before and at regular intervals after the administration of captopril, an orally active inhibitor of angiotensin I-coverting enzyme, to 12 salt-replete and six salt-deplete normal subjects. Concurrent measurements of active renin, angiotensin I and angiotensin II were also performed. Basal inactive renin in the salt-deplete group was increased compared with the salt-replete subjects, but inactive renin remained constant in both groups after treatment with captopril. There were significant increases in concentrations of both active renin and angiotensin I after treatment with captopril in all subject and corresponding decreases in angiotensin II. These results suggested that angiotensin II does not influence the release of inactive renin, in contrast with its role in the release of active renin. PMID- 6253588 TI - Further studies on the stimulation of rat adrenal capsular cells: four types of response. AB - Preparations of capsular rat adrenal cells consisting mainly of zona glomerulosa with less than 5% zona fasciculata contamination are described. The responses of the aldosterone and corticosterone outputs of these preparations to various stimuli were of four types. (1) Variations in K+ concentration gave a maximum aldosterone response at 5.9-8.4 mM-K+, about sixfold greater than the control output at 3.6 mmol/l. At higher K+ concentrations such as 13 mmol/l, the response decreased. (2) Serotonin (at a concentration of about 10(-4) mol/l) gave only a slightly lower maximal aldosterone response than did K+ but this did not decrease significantly at higher concentrations. Serotonin gave significant steroidogenic response at 10(-8) mol/l. (3) [Asp1,Val5]-Angiotensin II (10(-10) mol/l) with 3.6 mM-K+ gave a significant response and a constant maximal response at 2.5 x 10(-8) mol/l. This maximum response was about half that found for both aldosterone and corticosterone when stimulated maximally by K+ or serotonin: [des-Asp1,Ile5]- and [des-Asp1,Val5]-angiotensin II (angiotensin III) gave similar response characteristics but had a lower potency in this cell preparation. The initial maximum response could be further increased at a higher concentration (from 2.5 x 10(-5) mol/l) of a preparation of [Asn1,Val5]-amide angiotensin II (Hypertensin Ciba) and might eventually be greater than with K+. This additional response was, to a major extent, due to stimulation of the contaminating zona fasciculata cells and was not seen with high concentrations of the free acid, angiotensin II. It was also not seen in two experiments with pure [Asn1]-amide angiotensin II and therefore it could have been due to some impurity in Hypertensin-Ciba. (4) Adrenocorticotrophin (Synacthen) at 3 x 10(-11) mol/l gave a significant steroidogenic response. Higher concentrations (3 x 10(-10) to 7.5 x 10(-9) mol/l) gave no constant maximum but the response could be much greater than for other stimuli such as K+, serotonin and [Asp1]-angiotensin II. This additional response was again due to steroid precursors, e.g. deoxycorticosterone and corticosterone from contaminating zona fasciculata cells. Similar results were obtained with ACTH (ACTHAR) in three experiments. Threshold sensitivity (a significant increase in steroidogenesis) for ACTH (Synacthen) was, in two experiments, greater for zona fasciculata-reticularis cells (3 x 10(-12) mol/l) than for zona glomerulosa cells (3 x 10(-11) mol/l). The data show that aldosterone output was approximately a function of the square of the corresponding corticosterone value. Specific effects on this pathway can be shown by values of aldosterone/corticosterone2 greater than one. Of all stimuli used, only K+ concentrations of 5.3, 5.9 and 13 mmol/l gave such effects. However, because of several considerations, only positive results with other stimuli may be meaningful. Calculation of this parameter might be useful as a screening test in bioassays for substances with aldosterone-stimulating activity. PMID- 6253589 TI - Modulation of cyclic AMP in isolated rat uterine tissue slices by porcine relaxin. AB - Porcine relaxin produced a rapid, dose-related rise of cyclic AMP values in rat uterine tissue incubated in vitro. In time-course experiments, peak cyclic AMP concentrations were observed in the uterine slices at 5 min; subsequently the values fell, at first rapidly and then more slowly with the tissue concentration remaining significantly raised at 15 min. Levels of cyclic GMP in the same tissue slices were not significantly altered by relaxin. Furthermore, no increase in basal cyclic AMP values was measured in control slices prepared from the rat heart or jejunum. An increase in cyclic AMP concentration comparable to that found in the rat uterus was observed in slices of porcine uterus and cervix but not of vagina when they were stimulated with porcine relaxin. Our results suggest that the hormonal action of relaxin on the uterus and cervix is mediated through receptors linked to the enzyme, adenylate cyclase. PMID- 6253590 TI - Influence of stress on the secretion of corticosterone in the duck (Anas platyrhynchos). AB - The influence of stress on the secretion of corticosterone has been investigated by radioimmunoassay in domestic ducks (Anas platyrhynchos) of 6-8 weeks of age. Intravenous and i.m. injections of synthetic ACTH (Synacthen, 25 i.u./bird and Synacthen Depot, 100 i.u./bird respectively) markedly increased (2.7- to 10-fold) basal concentrations of corticosterone in plasma (3-6 ng/ml) in comparison with those in birds injected with 0.9% saline (1 ml/bird). Maximum levels of 30-40 ng/ml plasma were reached after 30 min and 5 h respectivley. Increased levels of corticosterone in plasma were also seen within 5 min of i.v. administration of saline and remained as high as those in birds treated with Synacthen for at least 20 min after injection. Blood sampling (from the brachial vein) was, by itself, sufficient to increase levels of corticosterone in plasma; a large (twofold) rise being observed as soon as 1 min after initial handling and bleeding, with concentrations of 30-40 ng/ml being found in birds bled 15 times during a period of 14 min. However, in a flock of birds, the alarm created in unhandled birds while others were being bled had no effect on concentrations of corticosterone in plasma. Deprivation of food or water for 24 h also enhanced levels of corticosterone in plasma, as did 24 h of adaptation to 0.2 M-NaCl drinking water. These results have demonstrated the lability of the secretion of corticosterone in response to stress and demonstrated its usefulness as a physiological indicator of stress in ducks. PMID- 6253591 TI - Prolactin receptors in the rat kidney. AB - Specific binding of 125I-labelled ovine prolactin iodinated by a lactoperoxidase method was demonstrated in crude membrane preparations of kidneys and adrenals of male Sprague-Dawley rats and livers from female rats. Membrane preparations derived from the 100,000 g fractions of tissue homogenates contained most of the specific prolactin binding. Kinetic and affinity characteristics of prolactin binding to kidney membranes were examined in detail. Maximal specific binding occurred after incubation for 30 h at room temperature. Scatchard analysis indicated that prolactin binding to kidney membranes was of high affinity (dissociation constant = 1.4 x 10(-10) mol/l) and similar to that for liver membranes, although kidney membranes from male rats bound approximately sixfold less prolactin/mg membrane protein than did liver membranes from female rats. Specific prolactin binding was demonstrated in both renal medulla and cortex. Autoradiography showed maximal prolactin binding activity in the epithelial cells of the proximal tubule and faint activity in the tubular cells throughout the nephron. Specificity of uptake by proximal tubular cells was indicated by the gross reduction in prolactin activity when excess ovine prolactin was administered simultaneously. The demonstration of specific binding sites for prolactin localized primarily in the proximal tubules was consistent with renal action of prolactin, predominantly on sodium metabolism. PMID- 6253592 TI - Suppression by organochlorines of the response to adrenocorticotrophin of the interrenal tissue in Sarotherodon aureus (Teleostei). AB - Superfused interrenal tissue of Sarotherodon aureus responded to ACTH with increased release of cortisol. The response to ACTH of interrenal tissue taken from fish treated with the organochlorine insecticide 1,1-dichloro-2-(o chlorophenyl)-2-(p-chlorophenyl) ethane (o,p-DDD; 50 mg/kg) in vivo was almost totally abolished. Lower doses were less effective. The response was also suppressed by exposure in vitro of the interrenal tissue to the organochlorine; there seemed to be a dose-response to o,p-DDD over the range of 0.023 to 1 mg/l. Also 1,1-dichloro-2,2-bis (p-chlorophenyl) ethylene (p,p'-DDE) was effective in suppressing the response to ACTH at concentrations of 50--150 mg/l; 1,1,1 trichloro-2,2-bis (p-chlorophenyl) ethane (p,p'-DDT) or the polychlorinated biphenyl, Aroclor 1254, were ineffective at 50 mg/l. No suppressive effect of o,p DDD on output of cortisol could be detected in superfusion when N6,O2'-dibutyryl cyclic AMP (20 mmol/L) was substituted for ACTH. This may indicate that the interference of o,p-DDD with the interrenal response to ACTH results from an interruption in the generation of cyclic AMP. PMID- 6253593 TI - Progesterone production by dispersed cells from human corpus luteum: stimulation by gonadotrophins and prostaglandin F 2 alpha; lack of response to adrenaline and isoprenaline. AB - Progesterone production was assessed following short-term incubations of luteal cell suspensions prepared from tissue samples of human corpora lutea obtained at specific times throughout the luteal phase of the menstrual cycle. Luteal cells responded rapidly and sensitively to human chorionic gonadotrophin (HCG: concentration required for 50% maximum response, 0.1--1.0 i.u./ml) with a maximum level of response (five- to tenfold higher than basal production) similar to that elicited by human LH or N6,O2'-dibutyryl cyclic AMP. In the absence of gonadotrophin or in the presence of sub-maximal (but not maximal) concentrations of HCG, progesterone production by mid-luteal phase cells was stimulated by prostaglandin F 2 alpha (1 mumol/l, an effect not observed during the late-luteal phase. L-Adrenaline and L-isoprenaline failed to elicit significant increases in the level of progesterone production. PMID- 6253594 TI - Inhibition by normal immunoglobulins of thyrotrophin-stimulated production of cyclic AMP in slices of normal human thyroid. AB - Slice preparations of normal human thyroid tissue have been used to investigate the effect of normal immunoglobulin G (IgG) on thyrotrophin (TSH)-induced accumulation of cyclic AMP. Incubation of slices in the presence of both TSH and normal IgG for 20 min reduced the stimulation of cyclic AMP accumulation elicited by TSH alone by approximately 30%. However, preincubation of slices with IgG for 100 min before addition of TSH virtually abolished the response to TSH. The latter effect of normal IgG was reversible, and removal of IgG before exposure to TSH allowed an unimpaired cyclic AMP response to TSH. The implications of these observations with respect to the application of this system to the functional bio detection of thyroid-stimulating antibodies in IgG fractions from thyrotoxic sera are discussed. PMID- 6253595 TI - Automated method for the determination of 5'-nucleotidase in serum by continuous flow analysis. AB - The manual method of Persijn & Van der Slik (J. Clin. Chem. Clin. Biochem. 6, 441 446 (1968): 7, 493-497 (1969); 8, 398-402 (1970) for the determination of serum 5'-nucleotidase has been adapted to the Auto-Analyzer II System. In the Auto Analyzer II, the incubation temperature for the enzyme reactions is 37 degrees C, and the effective sample speed is 30/h, at a sample/wash ratio of 2:1. There is good agreement and correlation between the manual method and the Auto-Analyzer II method (equation of regression line: y = x + 0.6, correlation coefficient = 0.988; the normal range is 2.9-10.5 U/l for both methods). In routine use, within run and between-day reproducibility are considerably smaller for the Auto Analyzer II than for the manual method, especially when large numbers of samples are assayed. PMID- 6253596 TI - [Primary hyperparathyroidism (author's transl)]. PMID- 6253597 TI - The stimulus-secretion coupling of glucose-induced insulin release. XLIII. Na-Ca countertransport mediated by pancreatic islet native ionophores. AB - Native ionophores extracted from isolated pancreatic islets were able to transport Ca2+ from one aqueous medium into another across an organic immiscible phase. In the presence of a K+, Na+, Li+, or H+ gradient, Ca2+ was transported against its own concentration gradient from the medium of low monovalent-cation concentration to the opposite medium. The transport of Ca2+ was abolished by the organic calcium-antagonist suloctidil. These findings provide a model for the process of Na-Ca countertransport in islet cells and its inhibition in response to the conversion of nutrient secretagogues to their acidic metabolites. PMID- 6253598 TI - Plant anticancer agents. X. Lignans from Juniperus phoenicea. PMID- 6253599 TI - Transient radiation myelopathy: spinal somatosensory evoked responses following incidental cord exposure during radiotherapy. AB - Serial spinal somatosensory evoked potentials were recorded in six patients undergoing radiotherapy involving incidental spinal radiation. Two patients developed transient radiation myelopathy. No abnormality was found in the somatosensory evoked potentials throughout the study. PMID- 6253600 TI - A sensitive method for the detection and quantification of conduction deficits in nerve. AB - A method is described which characterises the conduction deficit of a nerve in terms of the distribution of the refractory periods of transmission (RPTs) of its constituent fibres. The RPT is a particularly sensitive index of conduction deficit and measures the ability of a nerve fibre to conduct pairs of closely spaced impulses. The distribution of RPT in the nerve is represented as a graph, the RPT spectrum. Although the RPT spectrum is derived from recordings of the monophasic compound action potential, it is independent of changes in the conduction velocity of the constituent nerve fibres. The method is a particular value in the investigation lf lesions which are short or in which only a small proportion of the fibres present are affected. An investigation is described which examines the similarity between the RPT spectrum, derived from recordings of the compound action potential, and the frequency distribution histogram of RPT derived from a study of individual fibres from the same nerve. A recent study (Smith and Hall 1980) has shown that when the conduction deficit resulting from a lesion is described in terms of the RPT spectrum, a close correlation can be drawn between the physiological properties of the nerve, its histological appearance at the lesion, and the severity of the resulting behavioural deficit. PMID- 6253601 TI - Nerve conduction during peripheral demyelination and remyelination. AB - The changes in the conduction properties of peripheral nerve fibres of the mouse were examined during the phases of segmental demyelination, and remyelination, following the intraneural injection of lysophosphatidyl choline (LPC). In this lesion the sequence of the morphological changes was well synchronised in the different calibre fibres and this permitted a closer correlation to be made between the histological and physiological events than has been possible with other experimental models. Conduction in the nerve fibres was blocked during demyelination and for 1--2 days after the axons were completely free of myelin. In many fibres, however, conduction was later restored at about the time the demyelinated axon membrane became reassociated with debris-free Schwann cells, but prior to remyelination; at this time the fibres were unable to conduct closely spaced impulses and the conduction velocity was low. During the subsequent period of remyelination the ability of the fibres to conduct closely spaced impulses was fully restored and the conduction velocity progressively increased; the remyelinated internodes remained both thinner and shorter than normal. The physiological properties of the fibres were described in terms of their refractory periods of transmission (RPTs) as well as their conduction velocities; only the description in terms of the RPT correlated well with the histological events and with the degree of the behavioural deficit. PMID- 6253602 TI - Distribution of neurofilaments in myelinated axons of the optic nerve of goldfish (Carassius auratus L.). AB - Neurofilaments were counted in myelinated axons of the optic nerve of goldfish which were acclimated to 5 degrees and 25 degrees C. The number of neurofilaments increases markedly with increasing axonal size; axons of less than 0.1 micrometer 2 in area contain between 25 and 60 neurofilaments, while in the larger axons of area greater than 1.0 micrometer 2 there are approximately 190. The densities of the neurofilaments in the small axons are noticeably higher than in the larger ones (507 and 160, respectively). A variety of fixation procedures i.e. osmium tetroxide (OsO4) in phosphate buffer, glutaraldehyde (4%) in phosphate buffer or in ethyleneglycol-bis-(beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA) and piperazine-N-N'-bis-(2-ethanesulphonic acid) (PIPES) and post-fixed with OsO4 had no effect on the numbers of neurofilaments relative to the size of axon. The anaesthetic MS-222 (tricaine methanesulphonate) likewise had no effect on the numbers of neurofilaments. It is proposed that temperature acclimation alters the axon diameter concomitant with an alteration in the number of neurofilaments to fit the new diameter of the axons. PMID- 6253603 TI - Muscle fructose 1,6-diphosphatase deficiency associated with an atypical central core disease. AB - A 25-year-old woman with a non-familial congenital nonprogressive myopathy was found to have atypical core-like lesions in type 1 muscle fibers. Typical core lesions (approximately 13 micrometers in diameter) and smaller, PAS positive (4.1 micrometers in diameter) atypical core were associated with a predominant type 1 fibre myopathy. A specific deficiency of fructose 1, 6-diphosphatase was found with normal values for nine other muscle glycolytic and mitochondrial marker enzymes. The data provide evidence for a specific muscle enzyme deficiency in a patient with atypical central core disease. PMID- 6253604 TI - Postspike facilitation of forelimb muscle activity by primate corticomotoneuronal cells. PMID- 6253605 TI - Functional classes of primate corticomotoneuronal cells and their relation to active force. PMID- 6253606 TI - Effects of barium on cat spinal motoneurons studied by voltage clamp. PMID- 6253607 TI - Interstitial brachytherapy of primary brain tumors. Preliminary report. AB - Ten patients harboring inaccessible, slow-growing or recurrent malignant primary brain tumors were treated by the stereotaxic implantation of a radionuclide seed - iridium-192 (192Ir) or gold-198 (198Au) -- either permanent or removable. The strength for 192Ir seeds was selected to deliver 10,000 to 12,000 rads to the periphery of the tumor, and that for 198Au seeds to deliver 4000 to 7500 rads. Three of the six patients treated with 192Ir showed objective responses lasting 8, 11, and 12 months, respectively; and one patient's disease stabilized for 18 months. Three of the four treated with 198Au showed responses lasting 5 months, 6 months, and 2 years, respectively. Because of the higher dose-rate attainable with 198Au, removable implants of this material are more effective against the faster-growing malignant tumors. Another radionuclide, iodine-125 (125I), is now being tested against brain tumors. The radioactivity of 125I is high; but because its gamma emission is less energetic by a factor of 10 than that of 198Au or 192Ir, its radiation field is concentrated within a radius of 2.5 cm or less. This low-energy gamma emission also makes it easier to protect medical personnel and the patients' families against the nuclide when 125I is used. PMID- 6253608 TI - A study of the mineral phase of pulp calcification. AB - Physico-chemical properties of pulp calcification were studied by means of X-ray microbeam diffraction, electron spin resonance (ESR), X-ray energy-dispersive analysis, and chemical analysis. The material was obtained from the second molar of the right mandible of a 25-year-old woman. X-ray diffraction and ESR analyses showed that calcium salts of the calcification are deposited in the form of apatitie, possibly carbonate-containing apatite. Furthermore, the mineral phase of the calcification was found to be similar to that of bone rather than that of dentin with regard to crystallinity and inorganic content. An unexpected finding was that high concentrations of iron were detected in some areas near the surface of the calcification. The question remains open as to what role, if any, iron may play in the formation of pulp calcification. PMID- 6253609 TI - Oat cell carcinoma, phaeochromocytoma and carcinoid tumours--multiple APUD cell neoplasia--a case report. AB - A case of non-familial multiple APUD cell neoplasia is described in which an oat cell carcinoma occurred in association with a phaeochromocytoma and two gastric carcinoids. This is the first reported case in which an oat cell carcinoma has formed part of such a syndrome. The arguments for and against this being a chance association are briefly stated and it is suggested that this case provides some support for the view that oat cell carcinomas are themselves derived from APUD cells. The same patient had autoimmune disease, and although this may be purely fortuitous, a speculative hypothesis is advanced suggesting that the deranged anterior pituitary trophic function seen in Hashimoto's thyroiditis may have predisposed to multiple endocrine neoplasia in this case. PMID- 6253610 TI - Langerhans' cells in a pleomorphic adenoma of submandibular salivary gland. AB - Large numbers of round and dendritic cells similar to Langerhans' cells of normal epidermis and other epithelia were seen within a pleomorphic adenoma of the submandibular salivary gland. These cells, which were present only in areas of non-cornifying epidermoid metaplasia, exhibited Birbeck granules with isolated terminal vesicles, cytoplasmic microfilaments, microtubules, and a few poorly developed intercellular junctions. PMID- 6253611 TI - Coxsackie virus B3 perimyocarditis in BALB/c mice: experimental model of chronic perimyocarditis in the right ventricle. AB - Severe perimyocarditis was induced in weanling BALB/c mice inoculated with Coxsackie virus B3 (Nancy strain). Yellowish-white patches were seen only on the surface of the right ventricle of the heart on the 7th to the 180th day after the inoculation. More than half the animals were affected. Following myocardial degeneration and necrosis, mononuclear cell infiltration was evident on the 7th day. After the 28th day, perimyocardial fibrosis increased and cellular infiltration gradually decreased. Marked perimyocardial fibrosis with calcification which was limited to the right ventricle was observed 90 days after inoculation and persisted to the 180th day. This animal model enables studies on the natural history of perimyocarditis of viral aetiology and its possible sequels, chronic or constrictive pericarditis, in humans. A possible role of Coxsackie virus infection in the pathogenesis of idiopathic right ventricular myocardial hypoplasia in association with right ventricular dilatation in man (Uhl's anomaly) is discussed. PMID- 6253612 TI - An unusual case of supraclavicular and colonic malakoplakia--a light and ultrastructural study. AB - A case of malakoplakia of the supraclavicular region and colon in a 41-year-old patient is presented. Clinical, histopathological, histochemical and ultrastructural features are described. The etiology and pathogenesis are discussed. Malakoplakia is a chronic inflammatory disorder probably due to an abnormal response to infection with Gram negative bacteria, most likely Escherichia coli or Klebsiella. The disease is characterised by the accumulation of macrophages intermixed with plasma cells and lymphocytes. The malakoplakic cells are laden with phagolysosomes which may provide a suitable biochemical environment for the deposition of calcium to form the pathognomonic Michaelis Gutmann bodies. Ultrastructural examination enhances the accuracy of diagnosis since it highlights the presence of lysosomes, phagolysosomes, Michaelis-Gutmann bodies, and intact E. coli or their remnants. PMID- 6253613 TI - Immunohistochemical staining of the Dutcher-Fahey intranuclear inclusion body in a case of Waldenstrom's macroglobulinaemia. AB - Thirteen years after the patient's death, tissues removed at biopsy and autopsy from a case of Waldenstrom's macroglobulinaemia have been shown to contain intranuclear inclusion bodies composed mostly of IgM-kappa immunoglobulin. They were demonstrated by staining the tissues by peroxidase-antiperoxidase methods. A few intranuclear inclusions stained for IgG and for lambda light chains. These findings suggest that the patient's condition may have been initially polyclonal and benign, but had become virtually monoclonal and neoplastic at the time of death 23 months later. The findings lend a little support to the suggestions of other workers that the Dutcher-Fahey inclusion body is unlikely to be specific for macroglobulinaemia. Nevertheless, these inclusion bodies appear to be pertinent to the assessment of this case, in view of the marked bias towards IgM kappa monoclonal gammopathy, which was not evident from a study of the cytoplasmic staining results alone. PMID- 6253614 TI - Detection of heterozygotes for congenital adrenal hyperplasia: 21-hydroxylase deficiency-a comparison of HLA typing and 17-OH progesterone response to ACTH infusion. AB - We have studied nine families in which at least one member has congenital adrenal hyperplasia, to compare the predictive value of HLA typing and the 17-hydroxy progesterone response to ACTH as methods for detection of heterozygotes. In each of six families, two children were affected and were HLA genotypically identical. None of the unaffected siblings were HLA identical with their affected siblings. When the 17-OHP response to ACTH and the HLA haplotypes of parents and unaffected siblings were compared, there was a 79% concordance for identification of heterozygotes. Two siblings were carriers according to HLA typing, but had normal 17-OHP responses consistent with the carrier state. Three individuals with recombinations involving the HLA region of chromosome number 6 were detected. Analysis of these recombinant individuals provided additional evidence suggesting that the 21-OH degrees gene is closely associated with the B-locus of HLA. When an affected individual has been identified, HLA typing is a direct and reliable method for determining the carrier state among family members. PMID- 6253615 TI - New transfusion program for an intensive care nursery. AB - We have established a new transfusion program for an intensive care nursery which is based on crossmatching several infants to the same unit of type O Rh0(D) negative packed red blood cells, dividing the unit into quadpacks, and allowing multiple entry into each quadpack over a 24-hour period in the nursery. With this procedure, each donor unit can be used to provide multiple transfusions to four infants over a four-day period. Follow-up of transfusion recipients revealed that 20% had evidence of previous or ongoing CMB infection at 10 months of age, a prevalence comparable to that for transfused infants in other studies. We found no evidence for transmission of HB infection and a low risk of allosensitization to red cell and lymphocyte antigens. PMID- 6253616 TI - The acetylcholine channel open time in chick muscle is not decreased following innervation. AB - 1. The mean channel open time (tau) of ACh receptors was measured in chick muscles at various stages of development. Tau was estimated by analysing ACh induced current fluctuations recorded extracellularly from small (ca. 20 micrometers2) membrane patches. 2. At random sites on uninnervated, embryonic chick muscle fibres in vitro, tau was relatively long--4 msec at 23 degrees C. 3. Estimates of tau at synaptic sites on embryonic myotubes innervated in vitro were identical to estimates at extrasynaptic sites on the same fibres. Both were comparable to estimates on uninnervated myotubes. 4. Synaptic currents at cultured junctions decayed slowly as simple exponentials. The decay time constants were never shorter than the mean channel open time measured by fluctuation analysis. 5. In anterior latissimus dorsi and intercostal muscle fibres of 4- to 18-week posthatched chicks, fluctuation analysis and synaptic current decays indicate that the channel open time of mature chick endplate receptors is as long as that of embryonic synaptic receptors in vitro. Apparently, tau remains prolonged throughout the maturation of chick neuromuscular junctions. PMID- 6253617 TI - A post-natal decrease in acetylcholine channel open time at rat end-plates. AB - 1. The mean channel open time (tau) of ACh receptors in adult developing rat skeletal muscle was estimated by analysis of ACh current fluctuations. 2. At adult end-plates, tau was 1.4 msec at 21 degrees C. Time constants of miniature end-plate current decays (taus) were equally brief. 3. On the other hand, tau and taus were long (4.5 msec, 21 degrees C) at neonatal rat end-plates. These estimates are comparable to values obtained at extrajunctional sites on embryonic rat myotubes grown in culture and on adult denervated muscle fibres. 4. Both tau and taus decreased to values characteristic of adult end-plates during the first 2 weeks after birth. 5. Complex ACh power spectra were obtained at most end plates during the transition period and at some, miniature synaptic current decays were doubly exponential. End-plates in transition might contain a mixture of slow, neonatal channels and fast, adult channels. PMID- 6253618 TI - Acetylcholine sensitivity of developing ectopic nerve-muscle junctions in adult rat soleus muscles. AB - 1. The development of junctional ACh sensitivity has been studied during the formation of ectopic nerve-muscle junctions (n.m.j.s) between the superficial fibular nerve and the denervated soleus muscle of adult rats. 2. When the soleus nerve was cut 2 weeks or more after implanting the fibular nerve, spontaneous m.e.p.p.s and evoked e.p.p.s were first detected in the vicinity of the fibular nerve sprouts 2.5-3 days later. At this time, peaks of local ACh sensitivity greater than the high level of extrajunctional sensitivity induced by denervation were found near the sprouts of the fibular nerve. 3. During the first week of foreign innervation, the extrajunctional sensitivity of the newly innervated muscle fibres fell, but the peaks of sensitivity in the region of the fibular nerve sprouts persisted. Many of these peaks occurred at sites of transmitter release from the fibular nerve terminals. Each innervated fibre had from 1-8 such peaks. 4. When the fibular nerve was cut 2 days or more after cutting the soleus nerve peaks of ACh sensitivity persisted in the region of the degenerated foreign nerve terminals even if the extrajunctional sensitivity was abolished by direct electrical stimulation of the muscle starting soon after cutting the fibular nerve. 5. When the fibular nerve was left intact, more than half of the peaks of sensitivity formed initially in the region of the foreign nerve sprouts had disappeared 2-3 weeks after cutting the soleus nerve. 6. We conclude that during the formation of ectopic n.m.j.s in adult rat muscle the foreign nerve terminals bring about two types of long-lasting change in the distribution and stability of the underlying ACh sensitivity in the muscle fibre membrane; an increase and stabilization of sensitivity at sites of transmitter release which occurs by the time functional transmission at the newly formed n.m.j.s can be detected, and a loss of sensitivity at some of the sites which takes place about 1-2 weeks later. PMID- 6253619 TI - Control of junctional acetylcholinesterase by neural and muscular influences in the rat. AB - 1. The development of AChE at ectopic neuromuscular junctions forming between a transplanted foreign nerve (the superficial fibular nerve) and the denervated soleus muscle has been studied in adult rats. 2. Junctional AChE activity began to appear in the vicinity of the fibular nerve sprouts 6-7 days after section of the soleus nerve and 3-4 days after the onset of transmission. 3. No histochemically detectable AChE appeared when the fibular nerve was cut 0-4 days after the soleus nerve had been cut. 4. Direct electrical stimulation of the denervated soleus muscle caused plaques of true AChE, as determined by inhibitor studies, to appear in muscles where the fibular nerve had been cut 2-4 days after the soleus nerve but not in muscles where the two nerves had been cut at the same time. The plaques appeared only in the vicinity of fibular nerve sprouts and coincided with newly formed but stable peaks of ACh sensitivity. Local application of Neostigmine prolonged and increased the depolarising response evoked by pulses of ACh at these sites. 5. In muscles where the fibular nerve was intact the AChE plaques changed gradually over a few weeks from an immature appearance to a mature appearance characteristic of normal end-plates. In stimulated muscles where the fibular nerve had been cut the plaques stained intensely but remained morphologically immature. 6. We conclude (1) that muscle activity is important for the appearance of AChE at developing neuromuscular junctions and (2) that AChE accumulates only at sites on the muscle surface where the nerve fibres have left a 'trace' upon contact with the muscle fibres. These traces form quickly and persist after nerve-muscle interaction of as little as 2 days. The muscle appears as a major source of junctional AChE since stimulation of the muscle induces intense AChE activity in muscles where the nerve has degenerated. PMID- 6253620 TI - Phasic secretion of acetylcholine at a mammalian neuromuscular junction. AB - 1. The transient increase in secretion of quanta of acetylcholine (phasic secretion) produced by an action potential or brief depolarizing current pulse in mouse phrenic nerve terminals was examined. 2. Following an activating stimulus, there was a brief delay (minimum latency) followed by a sigmoidal increase in secretion which then decayed exponentially. 3. The minimum latency, rise time and rate of decay of phasic secretion, whether elicited by action potentials or electrotonic depolarization, were all extremely sensitive to temperature, with Q10s as high as 4 at temperatures of 5-15 degrees C. Arrhenius plots of results showed a change in slope with temperature, the change appearing most marked at 20 25 degrees C. 4. Phasic secretion in response to action potentials prolonged by inhibitors of K conductance (4-aminopyridine, uranyl, tetraethylammonium or Zn ions) showed an increase in minimum latency but no other change in time course. 5. Depolarizing pulses of varying width (0.2-2 msec) applied to nerve terminals (in the presence of tetrodotoxin and 4-aminopyridine) affected minimum latency, but had no great effect on the time course of phasic secretion. 6. Neither an increase in extracellular K ion concentration nor a decrease in pH had any effect on the time course of phasic secretion nor was any change produced by ethanol or octanol. 7. Variations in extracellular Ca concentration, substitution of Sr ions for Ca ions and repetitive stimulation, while producing changes in the magnitude of secretion, produced no change in the time course of phasic secretion. PMID- 6253621 TI - The action of serotonin in the rat hippocampal slice preparation. AB - 1. Intracellular activity was recorded from neurones in the CA1 pyramidal layer of slices of rat hippocampus maintained in vitro. 2. Application of 5-HT in a droplet or via ionophoresis produced a 3-5 mV hyperpolarization associated with a 30% decrease in input resistance. 3. The response to 5-HT was minimal with a drop concentration of 1 microM and maximal with 100 microM. The responses appeared to be blocked by methysergide applied in the superfusion medium. 4. The responses to 5-HT were minimal when the drug was applied in the apical dendritic region and maximal when it was applied near the soma. 5. 5-HT produced no substantial changes in e.p.s.p.s evoked by stimulation of the Schaffer collateral-commissural system or in i.p.s.p.s which were occasionally encountered following stimuli to the stratum radiatum. 6. The responses to 5-HT are true post-synaptic responses and are not indirect effects since they are present in a Ca2+-deficient Mg2+ enriched medium which blocks synaptic transmission. 7. The responses to 5-HT were not dependent on extracellular Cl- concentration. 8. These experiments indicate that 5-HT produces its effects in the rat hippocampus by activating K+ channels. PMID- 6253622 TI - Some properties of spontaneous excitatory junction potentials recorded from arterioles of guinea-pigs. AB - 1. Spontaneous excitatory junction potentials were recorded from electrically short segments of arterioles taken from the intestinal submucosa of guinea-pigs. 2. Histograms of the amplitudes of these spontaneous potentials were unimodal; their amplitudes often corresponded with the amplitudes of the smallest evoked potentials recorded from the same preparation. 3. The time courses of both spontaneous and evoked potentials were very similar and it is suggested that evoked potentials are made up by the simultaneous occurrence of several spontaneous potentials. 4. The mean quantal content of evoked potentials was always far fewer than the number of varicosities present in the preparations. 5. It is suggested that during neuromuscular transmission, transmitter is released at relatively few sites throughout the ground plexus for each nerve impulse. PMID- 6253623 TI - Temporal lobe epilepsy: a new entity in psychiatry. AB - There has been a scarcity of information in the nursing literature in regard to the psychiatric syndrome of temporal lope epilepsy. This paper attempts to describe the basic features of this disorder as well as its diagnosis and medical treatment. Guidelines for patient assessment and strategies for intervention are presented. PMID- 6253624 TI - A model for mental health education in Hispanic communities. PMID- 6253625 TI - Hospital treatment of borderline patients: toward a better understanding of problematic issues. PMID- 6253626 TI - Family aspects of trichotillomania. AB - This paper reports on the utilization of family system concepts in the understanding and treatment of trichotillomania. The paper discusses family interactional aspects of trichotillomania in four families as well as a description of assessment, intervention and follow-up procedures used with each family group. PMID- 6253627 TI - Women and mental illness: a sexist trap? PMID- 6253628 TI - Implications for sensory motor therapy with emotionally disturbed children. PMID- 6253629 TI - Advocacy in family therapy. PMID- 6253630 TI - Adolescent ambivalence: a therapeutic issue. PMID- 6253631 TI - A mechanism of direct photoreduction of ferricytochrome c. PMID- 6253632 TI - Opioid peptides and pituitary function. PMID- 6253633 TI - Ovarian cAMP and cGMP fluctuations in the hamster during the oestrous cycle. AB - Cyclic GMP, cAMP and total DNA levels were determined in whole hamster ovaries on each day of the 4-day cycle. Pro-oestrous ovaries were removed during the time of the preovulatory LH surge (confirmed by RIA). Cyclic AMP levels (pmol/mg DNA) were highest during pro-oestrous (1268.0 +/- 139 (s.e.m.)) and lowest during dioestrus 2 ( 266.9 +/- 22). Cyclic GMP (pmol/mg DNA levels were highest at dioestrus 2 (87.2 +/- 19) and lowest during oestrus (11.9 +/- 2). Similar patterns were obtained with total pmol/4 ovaries. However expressed, there was an inverse correlation of cAMP and cGMP at dioestrus 2 (P < 0.02) and pro-oestrus (P < 0.001). Cyclic GMP was inversely correlated with total DNA levels (P < 0.02) at oestrus and dioestrus 2. PMID- 6253634 TI - Purification and characterization of calmodulin from sea urchin spermatozoa. AB - Calmodulin was purified to apparent homogeneity from sea urchin spermatozoa by heat-treatment at 85 degrees C, ammonium sulphate precipitation at pH 4.2, DEAE Sephacel chromatography and gel filtration on Sephadex G-100. Approximately 8.3 micrograms calmodulin were recovered per 10(10) sperm cells. The sperm calmodulin had an apparent molecular weight of 17 800. The purified calmodulin activated calmodulin-deficient phosphodiesterase from pig coronary arteries, with half maximal activation occurring at approximately 40 ng calmodulin/ml. Trifluoperazine also inhibited the sperm calmodulin activity. These results demonstrate that calmodulin is present in high amounts in sea urchin spermatozoa, and that it is essentially the same as the calmodulin isolated from various other tissues. PMID- 6253635 TI - Luteal LH receptors during the oestrous cycle and early pregnancy in the pig. AB - The concentration, affinity constant and occupancy of the LH receptor have been measured in corpora lutea, from 29 pigs at Days 6--16 of the oestrous cycle, and from 25 pigs at Days 12--30 of pregnancy, by using 125I-labelled porcine LH tracer. Investigation of the specificity of the receptor showed that cross reactions of other pituitary hormones were accounted for by their contamination with LH. Luteal concentration of unoccupied receptors doubled between Days 6 and 10 of the cycle, and decreased between Days 12 and 14; it increased 3-fold between Days 20 and 30 pregnancy, but was lower on Day 12 of pregnancy than at a comparable stage of the cycle. Concentrations of receptors occupied by LH increased early in the oestrous cycle, in parallel with the total receptor concentration; in pregnancy the percentage occupancy dropped dramatically as total receptor concentration increased between Days 20 and 30. Receptor affinity constants increased towards the end of the cycle and decreased between Days 20 and 30 of pregnancy. It is suggested that (1) the lower concentration of receptors in early pregnancy may reflect down regulation by circulating LH, concentrations of which are higher in early pregnancy than during the cycle; (2) the increase in receptor concentration between Days 20 and 30 or pregnancy may be due to a rise in circulating oestrogen levels; and (3) the decrease in occupancy at this time may be caused either by a decrease in affinity constant or by placental production of a chorionic gonadogrophin-like compound. PMID- 6253636 TI - Activities of some metabolic enzymes in the small intestinal mucosa during pregnancy and lactation in the rat. AB - The food intake, gut weight, gut length, mucosal protein and mucosal activities of alkaline phosphate (EC 3.1.3.1), acid phosphate (EC 3.1.3.2), isocitric dehydrogenase (EC 1.1.1.42) and glucose-6-phosphate (EC 3.1.3.9) were measured in rats during pregnancy, lactation and after the young were weaned. In general, the quantities measured increased slightly during pregnancy and considerably during lactation, reaching maximum values during the 3rd weeks of lacation and falling more or less rapidly after the young were weaned to the same levels as those in unmated animals. However, the gut length and mucosal protein remained higher even 3 weeks after weaning, so that weight per unit length and specific enzyme activities (per mg protein) tended to be lower in mated than in unmated rats. Changes in the specific activities of enzymes indicate alterations of the metabolic function of the enterocytes during breeding similar to changes reported for digestive enzymes. It is suggested that the intestine may reflect changes that take place in the liver. PMID- 6253637 TI - Enhanced excitability of the uterus of the pregnant rabbit by imidazole stimulation of cyclic AMP phosphodiesterase. AB - Imidazole, at concentrations between 10(-3) and 10(-2) M, exerts a profound stimulatory effect on rabbit uterine strips obtained during pregnancy and studied isometrically in vitro. The action is not duplicated by N-alkylimidazoles which have greater potency as inhibitors of thromboxane synthetase but the effect of imidazole was antagonized by isoproterenol or theophylline. Biochemical analysis indicated that imidazole at concentrations greater than 5 x 10(-4) M stimulated both high and low affinity forms of cyclic AMP phosphodiesterase. The uterus of pregnant rabbits is profoundly refractory to any kind of pharmacological stimulation and the effects of imidazole, acting to stimulate phosphodiesterase, suggest that the integrity of the adenyl cyclase-cyclic AMP-protein kinase system is a necessary requirement for this organ to remain quiescent during pregnancy. PMID- 6253638 TI - Short-term effect of cyproterone acetate on testicular FSH binding in immature rats. AB - Male rats, aged 19 days, were injected with 1 mg cyproterone acetate, an antiandrogen, and killed 24 h later. In 9 out of 10 experiments this increased the apparent FSH-binding capacity by testicular tissue in vitro. In 4 out of 5 similar experiments, injection of 500 micrograms testosterone propionate caused a significant reduction in FSH binding. Observed changes were small but this does not preclude the possibility that androgens contribute to the physiological control of FSH receptor numbers. PMID- 6253639 TI - Increased incidence of symptomatic cholesterol cholelithiasis in perimenopausal women receiving estrogen replacement therapy: a retrospective study. PMID- 6253641 TI - The effect of potential agonists and phagocytic stimuli on the cyclic GMP concentrations in several macrophage populations. PMID- 6253640 TI - The role of estrogens in myeloperoxidase-mediated antimicrobial mechanisms. PMID- 6253642 TI - Cell-mediated immunity in experimental parainfluenza type 3 virus infection. AB - Local respiratory-tract infection was produced experimentally in guinea-pigs by intranasal instillation of a suspension of parainfluenza virus type 3. Histologically, interstitial pneumonitis developed within 10 days and persisted for at least 70 days. Cell-mediated immunity was measured at intervals for 70 days after infection. Dermal reactivity could not be elicited. Leucocyte migration inhibition and macrophage-migration inhibition were increased. Macrophage aggregation was present. Increased cell-mediated immunity could be transferred from infected donor animals to normal recipient animals by adoptive spleen-cell transfer even 60 and 70 days after infection. PMID- 6253643 TI - Pulse-label analysis and mapping of the two terminal regions of asynchronous complementary strand replication of mitochondrial DNA in transformed hamster cells. PMID- 6253644 TI - Fine structure of ribosomal RNA. III. Location of evolutionarily conserved regions within ribosomal DNA. PMID- 6253645 TI - Chracterisation of complete type II insertions in cloned segments of ribosomal DNA from Drosophila melanogaster. PMID- 6253646 TI - Localization of repetitive and unique DNA sequences neighbouring the rabbit beta globin gene. PMID- 6253647 TI - Intercistronic regions in phi X174 DNA. II. Biochemical and biological analysis of mutants with altered intercistronic regions between genes J and F. PMID- 6253648 TI - Conferral of transposable properties to a chromosomal gene in Escherichia coli. PMID- 6253649 TI - Experimental evaluation of the effective dielectric constant of proteins. PMID- 6253650 TI - Circular dichroism and spin-label studies of carp hemoglobin. PMID- 6253651 TI - Role of glycoproteins in the uptake of L-14C-leucine by a synaptosomal fraction. AB - The present study deals with the effect of modification of membrane glycoproteins on the accumulation of amino acids by isolated synaptosomal fractions, measured by the uptake of 14C-leucine. Superficial sugar receptors were modified by concanavalin A, neuraminidase, and neuraminidase followed by concanavalin A binding. It is demonstrated that neuraminidase treatment followed by concanavalin A binding results in significant diminution of 14C-leucine uptake. A similar effect was observed in experimental hypox followed by concanavalin A binding to isolated synaptosomal fractions. In this case, however, (Na+-K+) -ATPase activity remained unchanged. These results seem to indicate that 14C-leucine uptake was dependent on integrity of glycoprotein structure of synaptosomal membranes. PMID- 6253652 TI - Studies on AMP deaminase and 5'-nucleotidase in rat brain under different experimental conditions. AB - Adenosine monophosphate (AMP) deaminase and 5'-nucleotidase, the two enzymes involved in the disposal of AMP, have been detected in different regions of normal rat brain and in animals subjected to heightened neuronal activity (leptazol-induced convulsions) and to depression of the central nervous system (CNS) by the administration of barbiturates. They have also been estimated in the CNS of animals subjected to anoxia or treated with lithium and ammonium salts. The AMP deaminase activity was found to be highest in cerebellum and lowest in cerebral cortex, while the 5'-nucleotidase activity was found to be highest in brain stem and lowest in cerebellum. The AMP deaminase activity was elevated in all the regions of brain during the preconvulsive and convulsive periods. The activity returned to normal during recovery. The activity of 5'-nucleotidase was found to be depressed in the preconvulsive and post-convulsive periods. The enzyme was also found to be depressed in all the three regions after the administration of barbiturates. Administration of lithium or ammonium salts of induction of anoxic states resulted in an increase in the activity of AMP deaminase in all the three regions of brain. These results are discussed in relation to the probable production of cyclic AMP and cyclic guanosine monophosphate (GMP) which may have depressive and excitatory roles, respectively, in brain. It appears that increased AMP deaminase activity is associated with increased neuronal activity while depression of 5'-nucleotidase activity is associated with conditions of decreased CNS excitability. PMID- 6253653 TI - Experimental studies on TDI dermatitis in mice. AB - Allergic contact dermatitis occurred with 2, 4-toluene diisocyanate (TDI) in BALB/c mice. The results were obtained by the measurement of the ear thickness after challenged to the ear with 1% TDI in olive oil in mice previously sensitized with 5% TDI. The ear swelling rate at 48 hr postchallenge in sensitized mice was more than twice of that in unsensitized mice. In BALB/c-nu/nu (nude) mice, delayed type hypersensitivity could not be induced even when a 30% TDI solution was applied. These results suggest that T cells may play an essential role in contact sensitivity to TDI in BALB/c mice. PMID- 6253654 TI - Studies on the toxicity of coal-tar dyes. III. Reason of acute toxicity to fish caused by coal-tar dyes and their industrial effluents. AB - Reason of acute toxicity to fish caused by coal-tar dyes and their industrial effluents were studied from the three points of view. 1) Partition coefficient (n octanol/water) was determined on several coal-tar dyes, and it was found that the larger the ratio was, the stronger was toxicity to fish. 2) As a result of determination about existent form of xanthene dyes under photo-irradiation, it was clarified that dyes in solution were in the form of excited triplet state and halogen in dye molecule was liberated in free form. 3) When coal-tar dyes were treated with sodium hypochlorite, harmful chloroform was detected from dye solution. Chloroform and its homologous compounds showed the low TLm value and had the serious effect on fish. PMID- 6253655 TI - Chloroquine resistant malaria in Africa. PMID- 6253656 TI - High-resolution microanalysis of biological specimens by electron energy loss spectroscopy and by electron spectroscopic imaging. PMID- 6253657 TI - Separation of cyanogen bromide-cleaved peptides of the vesicular stomatitis virus glycoprotein and analysis of their carbohydrate content. AB - The purified glycoprotein of vesicular stomatitis virus was cleaved at methionine residues with cyanogen bromide, and the resultant peptides were analyzed by two dimensional electrophoresis in sodium dodecyl sulfate-polyacrylamide gels. Five peptide bands were resolved in cylindrical gels run under nonreducing conditions. After reduction and electrophoresis in the second dimension, 11 peptides were resolved, indicating that several were originally linked by disulfide bonds. Double-label experiments indicated that at least 8 of the 11 peptides were unique. The major oligosaccharide chains were attached to two different cyanogen bromide peptides. In addition, six other peptides contained small amounts of sialic acid, fucose, and mannose, indicating that the glycoprotein contains more carbohydrate chains than the two major ones which have been reported previously. PMID- 6253658 TI - Identification of the avian myeloblastosis virus genome. I. Identification of restriction endonuclease fragments associated with acute myeloblastic leukemia. AB - The proviral DNA of chicken peripheral blood leukemic myeloblasts was analyzed by restriction endonuclease digestion and Southern blotting. Two restriction endonuclease-generated fragments, an EcoRI 2.2-megadalton (Md) and a HindIII 2.6 Md fragment, were present upon enzyme cleavage of all leukemic myeloblast DNA preparations in addition to endogenous or helper-specific fragments. Neither of these fragments was derived from viral DNA of the two known myeloblastosis associated viruses (MAV-1 and MAV-2). In contrast, DNA similarly treated from the erythrocytes of leukemic chickens showed only small amounts of the two avian myeloblastosis virus-specific fragments, whereas the helper virus-specific fragments were present in the amount seen in MAV-producing chicken embryo fibroblasts. The appearance of the EcoRI 2.2-Md and HindIII 2.6-Md specific fragments in all leukemic myeloblast DNA preparations indicates they are presumably part of the leukemogenic genome that must be present to induce acute myeloblastic leukemia. PMID- 6253659 TI - Identification of the avian myeloblastosis virus genome. II. Restriction endonuclease analysis of DNA from lambda proviral recombinants and leukemic myeoblast clones. AB - Two lambda proviral DNA recombinants were characterized with a number of restriction endonucleases. One recombinant contained a complete presumptive avian myeloblastosis virus (AMV) provirus flanked by cellular sequences on either side, and the second recombinant contained 85% of a myeloblastosis-associated virus type 1 (MAV-1)-like provirus with cellular sequences adjacent to the 5' end of the provirus. Comparing the restriction maps for the proviral DNAs contained in each lambda hybrid showed that the putative AMV and MAV-1-like genomes shared identical enzyme sites for 3.6 megadaltons beginning at the 5' termini of the proviruses with respect to viral RNA. Two enzyme sites near the 3'-end of the MAV 1-like provirus were not present in the putative AMV genome. We also examined a number of leukemic myeloblast clones for proviral content and cell-provirus integration sites. The presumptive AMV provirus was present in all the leukemic myeloblast clones regardless of the endogenous proviral content of the target cells or the AMV pseudotype used for conversion. Multiple cellular sites were suitable for integration of the putative AMV genome and the helper genomes. The proviral genomes were all integrated colinearly with respect to linear viral DNA. PMID- 6253661 TI - Intracellular forms of simian virus 40 nucleoprotein complexes. III. Study of histone modifications. AB - The modification patterns of histones present in various forms of intracellular simian virus 40 nucleoprotein complexes were analyzed by acetic acid-urea polyacrylamide gel electrophoresis. The results showed that different viral nucleoprotein complexes contain different histone patterns. Simian virus 40 chromatin, which contains the activities for the synthesis of viral RNA and DNA, exhibits a histone modification pattern similar to that of the host chromatin. However, virion assembly intermediates and mature virions contain highly modified histones. Pulse-chase experiments with [3H]lysine showed that the newly incorporated histones in the virion assembly intermediates were already highly modified. The majority of in vivo acetylation activity of histones occurred on the 70S simian virus 40 chromatin as analyzed by pulse-labeling with [3H]acetate. These results and our previous analysis of the virion assembly pathway suggest that three stages are involved in the packaging of simian virus 40 chromatin into the mature virion: (i) modification of histones, (ii) accumulation of capsid protein around the chromatin with highly modified histones, and (iii) organization of capsid proteins into salt-resistant shells. The role of histone modification in virion assembly is discussed. PMID- 6253660 TI - Unique species of mRNA from adenovirus type 7 early region 1 in cells transformed by adenovirus type 7 DNA fragment. AB - Adenovirus type 7 (Ad7) early region 1 mRNA species transcribed in rat cell lines transformed by the HindIII-I . J fragment (the left 7.8% of the viral genome) and in human KB cells infected with Ad7 were mapped on the viral genome, using S1 nuclease gel and diazobenzyloxymethyl paper hybridization techniques. At the early stage of productive infection, two mRNA's (950 and 840 nucleotides long) with the common 5' and 3' ends but different internal splicings were mapped from region 1A (map units 1.4 to 4.3), and one mRNA (2,310 nucleotides long, with the internal splicing between map units 9.9 to 10.1) was mapped from region 1B (map units 4.6 to 11.4). At the late stage, these early spliced mRNA's were also found and at least three additional Ad7 mRNA's were identified: 700-nucleotide-long mRNA in region 1A; and 1,100- and nucleotide-long mRNA's in region 1B. In transformed rat cell lines, two early region 1A mRNA's (950 and 840 nucleotides long) were also transcribed. Surprisingly, in addition, several unique Ad7 mRNA's, not found in productivity infected cells, were identified in all of the transformed cell lines. Their molecular sizes and coding sequences varied in individual cell lines. However, these mRNA's had the 5' end-proximal portion in region 1B and the 3' end-proximal portion in region 1A, these portions being transcribed by extending from region 1B to 1A on viral DNA fragments joined in a tandem array in transformed cells. PMID- 6253662 TI - Herpes simplex virus thymidine kinase transcripts are absent from both nucleus and cytoplasm during infection in the presence of cycloheximide. AB - Nick-translated DNA from a recombinant plasmid containing the herpes simplex virus type 1 thymidine kinase gene was used as a probe for the synthesis of thymidine kinase RNA. The recombinant plasmid was generated by inserting the 3.5 kilobase fragment derived by BamHI digestion of herpes simplex virus type 1 DNA into plasmid pBR322. At 8 h after infection, cytoplasmic and nuclear RNA hybridized to 14% and 19% of the recombinant DNA probe, respectively. However, no significant hybridization was found with either nuclear or cytoplasmic RNA extracted from cells infected and maintained in the presence of cycloheximide. This suggests that no thymidine kinase-related RNA was synthesized in the absence of alpha polypeptides, and supports the hypothesis that the alpha polypeptides effect new thymidine kinase RNA synthesis rather than being involved in processing or transport of thymidine kinase RNA. In cells infected and maintained in the presence of the arginine analog canavanine, about 2 to 3% of the plasmid DNA was found to hybridize with cytoplasmic and nuclear RNA. However, when a recombinant plasmid DNA containing only thymidine kinase coding sequences was used, no significant hybridization was found. The inhibition of thymidine kinase transcription by canavanine suggests that thymidine kinase belongs to the beta 2 kinetic class. PMID- 6253663 TI - Abelson murine leukemia virus transformation-defective mutants with impaired P120 associated protein kinase activity. AB - Several transformation-defective (td) mutants of Abelson murine leukemia virus (AbLV) are described. Cells nonproductively infected with such mutants exhibited a high degree of growth contact inhibition, failed to form colonies in soft agar, lacked rescuable transforming virus, and were as susceptible as uninfected control cells to transformation by wild-type (wt) AbLV pseudotype virus. In addition, each of several td AbLV nonproductively infected cell clones analyzed was found to be nontumorigenic in vivo. Biochemical analysis of td mutant AbLV infected clones revealed levels of expression of the major AbLV translational product, P120, and a highly related 80,000-Mr AbLV-encoded protein, P80, at concentrations analogous to those in wt AbLV-transformed cells. Although the AbLV specific 120,000-Mr polyproteins expressed in td mutant AbLV-infected clones were indistinguishable from those in wt AbLV-transformed lines with respect to molecular weight and [35S]methionine tryptic peptide composition, they each differed from wt AbLV P120 in their patterns of post-translational phosphorylation. A previously described AbLV-associated protein kinase activity is shown to recognize as substrate a major tyrosine-specific acceptor site(s) contained within a single well-resolved tryptic peptide common to both AbLV P120 and P80. In vitro [gamma-32P]ATP-mediated labeling of this phosphorylation site was reduced to below detectable levels in td mutant nonproductively infected cell clones. These findings establish that the AbLV-encoded polyprotein P120 and its associated protein kinase activity are involved in AbLV tumorigenesis. PMID- 6253664 TI - Heterogeneity of the 3' end of minus-strand RNA in the poliovirus replicative form. AB - The 3' terminus of the strand (minus strand) complementary to poliovirion RNA (plus strand) has been examined to see whether this sequence extends to the 5' nucleotide terminus of the plus strand, or whether minus-strand synthesis terminates prematurely, perhaps due to the presence of a nonreplicated nucleotide primer for initiation of plus-strand synthesis. The 3' terminus was labeled with 32P using [5'-32P]pCp and RNA ligase, and complete RNase digests were performed with RNases A, T1, and U2. 32P-oligonucleotides were analyzed for size by polyacrylamide-urea gel electrophoresis. The major oligonucleotide products formed were consistent with the minus strand containing 3' ends complementary and flush with the 5' end of the plus strand. However, a variable proportion of the isolated minus strands from different preparations were heterogeneous in length and appeared to differ from each other by the presence of one, two, or three 3' terminal A residues. PMID- 6253665 TI - Cloning of human papilloma virus genomic DNAs and analysis of homologous polynucleotide sequences. AB - The complete DNA genomes of four distinct human papilloma viruses (human papilloma virus subtype 1a [HPV-1a], HPV-1b, HPV-2a, and HPV-4) were molecularly cloned in Escherichia coli, using the certified plasmid vector pBR322. The restriction endonuclease patterns of the cloned HPV-1a and HPV-1b DNAs were similar to those already published for uncloned DNAs. Physical maps were constructed for HPV-2a DNA and HPV-4 DNA, since these viral DNAs had not been previously mapped. By using the cloned DNAs, the genomes of HPV-1a, HPV-2a, and HPV-4 were analyzed for nucleotide sequence homology. Under standard hybridization conditions (Tm = --28 degrees C), no homology was detectable among the genomes of these papilloma viruses, in agreement with previous reports. However, under less stringent conditions (i.e., Tm = --50 degrees C), stable DNA hybrids could be detected between these viral DNAs, indicating homologous segments in the genomes with approximately 30% base mismatch. By using specific DNA fragments immobilized on nitrocellulose filters, these regions of homology were mapped. Hybridization experiments between radiolabeled bovine papilloma virus type 1 (BPV-1) DNA and the unlabeled HPV-1a, HPV-2a, or HPV-4 DNA restriction fragments under low-stringency conditions indicated that the regions of homology among the HPV DNAs are also conserved in the BPV-1 genome with approximately the same degree of base mismatch. PMID- 6253666 TI - Dual evolutionary origin for the rat genetic sequences of Harvey murine sarcoma virus. AB - Detailed restriction endonuclease maps were developed for Harvey murine sarcoma virus (Ha-MuSV) DNA (clone H-1), molecularly closed at its unique EcoRI site in pBR322, for three nonoverlapping subgenomic HindIII clones which together span the entire H-1 clone and for a molecularly cloned DNA copy of a portion of rat 30S RNA (which represents the majority of the rat genetic sequences in Ha-MuSV). Molecular hybridization of the 30S clone to small restriction fragments of clone H-1 revealed a 0.9-to-1.0-kilobase pair region in the 5' half of the Ha-MuSV genome not homologous to the 30S clone, although the 30S clone did contain related sequences in Ha-MuSV on both sides of this nonhomologous region. By using cloned sequences from a segment of the Ha-MuSV nonhomology region as a probe for hybridization to Southern blots of DNA from rat, mouse, bat, and chicken cells, one to three bands were detected in DNA of each species. By contrast, the 30S clone DNA was highly related to many sequences in rat DNA, partially related to fewer mouse DNA sequences, and homologous only to one to three bands in bat and chicken DNA. Earlier work had shown that the 5' half of the Ha-MuSV genome coded for transformation and for the viral p21 protein (Chang et al., J. Virol. 35: 76- 92, 1980; Wei et al., Proc. Natl. Acad. Sci. U.S.A., in press). We used two subgenomic HindIII clones whose shared HindIII site mapped within the 5' region of clone H-1 nonhomologous to the 30S clone to test whether the nonhomologous segment might encode the transforming and p21 functions. Although neither of the subgenomic HindIII fragments by themselves induced transformation, ligation of these two nontransforming DNAs to each other did restore p21-mediated transformation. A conclusion consistent with these results is that a region in the 5' half of the Ha-MuSV genome evolutionarily distinct from and not present in rat 30S RNA is essential for transformation and for p21 encoding. PMID- 6253667 TI - Factors which disorganize microtubules or microfilaments increase the frequency of cell transformation by polyoma virus. AB - Griseofulvin, 12-O-tetradecanoyl phorbol-13-acetate, melittin, epidermal growth factor, vinblastine, cytochalasin B, podophyllotoxin, colcemid, and colchicine were unable to transform cells but could increase from 8- to 40-fold the frequency of cell transformation by polyoma virus. The 3T3-like cells were resting at confluence and were exposed to the drug only during the 1st week after viral infection. Griseofulvin, a tumor promoter, reduced or increased the frequency of transformation depending on the dose with which the infected cells were treated. The antitumor activity of tumor promoters is discussed. PMID- 6253668 TI - Synthesis and processing of glycoproteins gD and gC of herpes simplex virus type 1. AB - Herpes simplex virus type 1 (HSV-1) contains five glycoproteins, designated gA, gB, gC, gD, and gE. The present studies focused on the synthesis and processing of two of these, gC and gD. By using monoprecipitin antibody to gC, we demonstrated an antigenic and structural relationship between the precursor, pgC(110), and the product, gC(130). Tryptic peptide analysis showed that pgC and gC shared methionine peptides and that these molecules had the same fingerprint pattern as that of gC(130) extracted from the purified virion. These results suggested that post-translational processing of gC involved no major changes in methionine-containing tryptic peptides or in the cleavage sites required to generate those peptides. The syntheses of gC and gD were compared. We found that the glycoproteins were synthesized starting at different times in the infectious cycle; pgD was detected by 2 h postinfection, whereas pgC was first detected at 4 to 6 h postinfection. Both precursor molecules, pgC(110) and pgD(52), are basic glycopolypeptides, and in both cases processing involved changes in molecular weight and charge. These changes were detected by two-dimensional gel electrophoresis. Both glycoproteins exhibited heterogeneity, displayed as a series of spots (6 for gD and 15 to 20 for gC) of increasing negative charge and molecular weight. Neuraminidase treatment decreased the size, number, and acidic charge of the spots, suggesting that processing was due in part, but not entirely, to addition of sialic acid to pgD and pgC. PMID- 6253669 TI - Coronavirus multiplication strategy. II. Mapping the avian infectious bronchitis virus intracellular RNA species to the genome. AB - Avian infectious bronchitis virus, a coronavirus, directed the synthesis of six major single-stranded polyadenylated RNA species in infected chicken embryo kidney cells. These RNAs include the intracellular form of the genome (RNA F) and five smaller RNA species (RNAs A, B, C, D, and E). Species A, B, C, and D are subgenomic RNAs and together with the genome form a nested sequence set, with the sequences of each RNA contained within every larger RNA species (D. F. Stern and S. I. T. Kennedy, J. Virol 34:665-674, 1980). In the present paper we show by RNase T1 oligonucleotide fingerprinting that RNA E is also a member of the nested set. Partial alkaline fragmentation of the genome followed by sucrose fractionation, oligodeoxythymidylate-cellulose chromatography, and RNase T1 fingerprinting gave a partial 3'-to-5' oligonucleotide spot order. A comparison of the oligonucleotides of each of the five subgenomic RNAs with this spot order established that all of the RNAs are comprised of nucleotide sequences inward from the 3' end of the genome. This result is discussed in relation to the multiplication strategy both of coronaviruses and of other RNA-containing viruses. PMID- 6253670 TI - Avian oncovirus mutant (SE21Q1b) deficient in genomic RNA: characterization of a deletion in the provirus. AB - We have previously described a nonconditional mutant of avian sarcoma virus (SE21Q1b) which fails to package viral RNA (Gallis et al., Virology 94:146-161, 1979; Linial et al., Cell 15:1371-1381, 1978). Quail cells transformed by SE21Q1b contain normal amounts of intracellular viral mRNA's for src, env, and gag-pol and release particles with the density of normal virus containing a typical complement of virion proteins, including reverse transcriptase. These virions are noninfectious for both chicken and quail cells and contain primarily cellular rather than viral RNA. Analysis by gel electrophoresis of the cellular DNA of quail cells transformed by SE21Q1b after restriction endonuclease digestion indicated the presence of a single provirus. The provirus was located at one site in the genome of the host cell and was flanked by the characteristic terminally repeated sequences derived from the 3' and 5' ends of viral RNA. The only defect detected in the SE21Q1b provirus was a deletion of ca. 150 base pairs of DNA somewhere between 300 and 600 bases from the left (gag-pol) end of the provirus. Analyses of the proviral DNA of cells transformed by wild-type recombinants between SE21Q1b and leukosis viruses reveal that the recombinants no longer contain this deletion. The deletion, therefore, defines a region on the viral RNA which is required for correct packaging of the virion RNA. PMID- 6253671 TI - Mechanism of inhibition of herpes simplex virus and vaccinia virus DNA polymerases by aphidicolin, a highly specific inhibitor of DNA replication in eucaryotes. AB - The inhibition in vitro of herpes simplex virus 1 and vaccinia virus DNA polymerases by aphidicolin is primarily noncompetitive with dGTP, dATP, dTTP, DNA, and Mg2+ and competitive with dCTP in analogy with the mode of inhibition of cellular alpha-polymerase. The degree of inhibition of viral or cellular growth in vivo can be quantitatively predicted by the degree of inhibition of the isolated replicative DNA polymerases at the same concentration of aphidicolin in suitable conditions (limiting dCTP concentration). Thus, the only in vivo target for aphidicolin is probably the replicative DNA polymerase, and aphidicolin is a highly specific inhibitor of replicative nuclear DNA synthesis in eucaryotes. This, coupled with the lack of mutagenic effect, represents a valuable property for an anticancer drug. The specificity of inhibition (contrary to the aspecific effect on almost all DNA polymerases by a true competitive inhibitor, such as 1 beta-D-arabinofuranosylcytidine 5'-triphosphate) and the structure of the drug, which does not resemble that of the triphosphates, suggest that aphidicolin must recognize a site common only to the replicative DNA polymerases of eucaryotes and different from the binding site for deoxyribonucleic triphosphates and DNA, which should be similar in reparative and procaryote-type DNA polymerase; the aphidicolin binding site is probably very near to, or even overlaping with, the binding site for dCTP so that the drug mimics a competitive effect with this nucleotide. PMID- 6253672 TI - Arrangement of the genome of the human papovavirus RF virus. AB - DNA from plaque-purified RF virus, a variant of BK virus, was found to contain two species of molecules. Hybridization of each DNA species to the fragments of BK virus DNA revealed that one species had a deletion corresponding to at least 50% of the late region and the other had a deletion corresponding to at least 40% of the early region of BK virus DNA. Analysis by cleavage of each RF virus DNA species with restriction endonucleases EcoRI, HindIII, AvaII, and PvuII, when compared with BK virus DNA, revealed that the size and number of fragments were different. These results suggest the loss of some restriction sites and the appearance of new sites, probably as a result of base changes in each RF virus DNA species. Furthermore, analysis of the restriction map of each DNA molecule revealed in insertion(s) in both DNA species. PMID- 6253673 TI - Close similarity between endogenous ecotropic virus of Mus musculus molossinus and AKR virus. AB - By using seven different restriction endonucleases, the cleavage patterns of the unintegrated provioral DNA from an ecotropic murine leukemia virus isolated from Mus musculus molossinus were found to be identical to those of AKR virus. An AKR [3H]DNA probe can be completely saturated with M. musculus molossinus and M. musculus castaneus DNAs, although the arrangement of viral sequences in M. musculus molossinus DNA differed from that of AKR virus. These studies indicate that an AKR-type ecotropic virus is present in some wild Asiatic mice. PMID- 6253675 TI - Characterization of tau antigens isolated from uninfected and simian virus 40 infected monkey cells and papovavirus-transformed cells. AB - Tau antigens (also known as cellular or nonviral tumor antigens) were detected in uninfected and simian virus 40-infected monkey cells after immunoprecipitation with serum from hamsters bearing simian virus 40-induced tumours (anti-T serum). These two proteins (56,000 daltons) were digested to similarly sized peptides with various amounts of Staphylococcus aureus V8 protease. The Tau antigen isolated from infected monkey cells was closely related but was not identical to the corresponding protein from human cells transformed by simian virus 40, as determined by two-dimensional mapping of their methionine-labeled tryptic peptides. Hamster cells transformed by various primate papovaviruses (simian virus 40, BK virus, and JC virus) synthesized indistinguishable Tau antigens, as determined by two-dimensional peptide mapping. When tested by the same procedure, these proteins and the ones made in monkey and human cells were found to be related to the Tau antigens isolated from simian virus 40-transformed mouse and rat cells. Based on these results, an "evolutionary tree" was constructed to show the relationship among the methionine-containing tryptic peptides of all of these proteins. PMID- 6253674 TI - Epstein-Barr virus RNA. V. Viral RNA in a restringently infected, growth transformed cell line. AB - A continuous lymphoblastoid cell line, IB-4, was established by infection and growth transformation of normal neonatal B lymphocytes with the B95-8 isolate of Epstein-Barr virus (EBV). The IB-4 cells contained the intranuclear antigen, EBNA, but not early antigen, EA. The fragments produced by the digestion of intracellular episomal viral DNA (density, 1.700 to 1.720 g/cm3) with EcoRI restriction endonuclease were identical in size to the A, B, C, E, F, G, and H fragments of virion DNA. As expected from the previous observation that episomal intracellular DNA is circular, the fragment containing the rightward terminal sequences of EBV DNA in IB-4 cells was larger than the corresponding fragment of linear viral DNA, probably as a consequence of covalent linkage to the leftward terminal fragment. Also, two fragments, EcoRI-I and -J, which were adjacent to each other in the virion DNA, were absent from the intracellular DNA. The labeled EcoRI-J of viral DNA hybridized instead to a new fragment equal in size to EcoRI I and -J combined. Analysis of viral RNA in IB-4 cells showed that RNAs encoded by more than 30% of the viral DNA comprised approximately 0.06% of the nuclear RNA, whereas RNAs encoded by 20% and 10% of the viral DNA comprised approximately 0.06% and 0.003% of the polyadenylated and polyribosomal RNAs, respectively. Viral mRNA (polyribosomal RNA) was encoded by DNA which mapped at 0.05 x 10(8) to 0.36 x 10(8) daltons and to a lesser extent by DNAs which mapped at 0.62 x 10(8) to 0.67 x 10(8), 0.70 x 10(8) to 0.73 x 10(8), and 1.13 x 10(8) to 1.15 x 10(8) daltons in the B95-8 genome. The most agundant nuclear viral RNAs were encoded primarily by DNA which mapped at the same loci; but RNAs encoded by many other fragments of viral DNA could also be detected among nuclear RNAs. Viral mRNA(s) (polyribosomal) was encoded by about 40% of the internal reiteration and by 25% of the BamHI-H fragments which mapped from 0.32 x 10(8) to 0.36 x 10(8) daltons, nuclear RNAs were encoded by at least 57% of the internal reiteration and 40% of BamHI-H. These data indicate that there is selective accumulation of some viral RNAs within the nucleus of IB-4 cells and that there is selective post transcriptional processing of these RNAs. Finer mapping of the DNA which encodes mRNA (polyribosomal) in IB-4 cells indicated that some of this DNA is deleted in the DNA of the P3 HR-1 virus, the only isolate of EBV which cannot initiate growth transformation. These data, therefore, support the hypothesis that expression of this region of EBV genome is important for growth transformation or for the maintenance of restrigent infection. PMID- 6253676 TI - BALB/c myeloma retroviruses have mink cell focus-inducing activity. AB - We have determined the in vitro host range of the cloned MO-21 and FL-1 murine myeloma retroviruses grown in SC-1 cells that were originally isolated from cloned MOPC-21 and FLOPC-1 BALB/c plasmacytoma cell lines. These viruses are able to replicate in murine (BALB/3T3, NIH/3T3) as well as numerous heterologous cell lines. These myeloma retroviruses also exhibit mink cell focus-inducing activity. MO-21 and FL-1 shared interference patterns with each other, but their replication was not interfered with by ecotropic, xenotropic, or amphotropic viruses. The lack of cross-interference with ecotropic or xenotropic viruses distinguishes these isolates from other mink cell focus-inducing viruses. PMID- 6253677 TI - A cloned polyoma DNA fragment representing the 5' half of the early gene region is oncogenic. AB - The two polyoma DNA fragments generated by cleavage with BamHI and EcoRI were cloned in pBR322, and their oncogenic potential was tested in vivo and in vitro. Only recombinant plasmid DNA containing a polyoma DNA fragment which extends clockwise from 58 to 0 map units and include approximately the 5'-proximal half of the early gene region produced tumors in newborn hamsters and transformed rat embryo cells in tissue culture. Southern blotting analysis indicated that the entire 2.2-kilobase polyoma BamHI-EcoRI fragment was intact in both a tumor cell line and a cell line transformed in culture which we examined. The presence of polyoma middle and small T antigen in these lines was demonstrated by immunoprecipitation and tryptic peptide mapping. DNA from a recombinant plasmid containing a polyoma genome deleted between 90 and 4 map units failed to induce tumors or transform cells. PMID- 6253679 TI - Generation of nondefective Rous sarcoma virus by asymmetric recombination between deletion mutants. AB - A replication-defective deletion mutant of Prague Rous sarcoma virus (RSV), which lacks functional gag, pol, and env genes, was crossed with a transformation defective deletion mutant derived from Schmidt-Ruppin RSV. Transformation- and replication-competent viruses were generated in the cross. Characterization of one of these rescued viruses indicated that it was a nondefective recombinant containing the src gene of the replication-defective mutant plus the replicative genes of the transformation-defective virus. These results indicate that, contrary to previous reports, asymmetric recombination between RSV deletion mutants can result in the formation of nondefective RSV. PMID- 6253678 TI - Molecular cloning of the avian erythroblastosis virus genome and recovery of oncogenic virus by transfection of chicken cells. AB - Avian erythroblastosis virus (AEV) causes erythroblastosis and sarcomas in birds and transforms both erythroblasts and fibroblasts to neoplastic phenotypes in culture. The viral genetic locus required for oncogenesis by AEV is at present poorly defined; moreover, we know very little of the mechanism of tumorigenesis by the virus. To facilitate further analysis of these problems, we used molecular cloning to isolate the genome of AEV as recombinant DNA in a procaryotic vector. The identity of the isolated DNA was verified by mapping with restriction endonucleases and by tests for biological activity. The circular form of unintegrated AEV DNA was purified from synchronously infected quail cells and cloned into the EcoRI site of lambda gtWES x B. A restriction endonuclease cleavage map was established. By hybridization with complementary DNA probes representing specific parts of avian retrovirus genomes, the restriction map of the cloned AEV DNAs was correlated with a genetic map. These data show that nucleotide sequences unique to AEV comprise at least 50% of the genome and are located approximately in the middle of the AEV genome. Our data confirm and extend previous descriptions of the AEV genome obtained by other procedures. We studied in detail two recombinant clones containing AEV DNA: the topography of the viral DNA in the two clones was virtually identical, except that one clone apparently contained two copies of the terminal redundancy that occurs in linear viral DNA isolated from infected cells; the other clone probably contained only one copy of the redundant sequence. To recover infectious virus from the cloned DNA, we developed a procedure for transfection that compensated for the defectiveness of AEV in replication. We accomplished this by ligating cloned AEV DNA to the cloned DNA of a retrovirus (Rous-associated virus type 1) whose genome could complement the deficiencies of AEV. Ligation of the two viral DNAs was facilitated by using a neutral fragment of DNA as linker between otherwise noncompatible termini. Cloned AEV DNA gave rise to infectious AEV capable of transforming fibroblasts and bone marrow cells in culture and of inducing both sarcomas and erythroleukemia in chickens. We conclude that the cloned DNAs represent the authentic genome of AEV undisturbed by the cloning procedure. Molecular cloning offers a powerful approach to the identification and characterization of retrovirus genomes. PMID- 6253680 TI - Leakage of nuclear transcripts late in simian virus 40-infected CV1 cells: quantitation of spliced and unspliced late 19S RNAs. AB - During the late phase of simian virus 40 infections of CV1 cells, the relative ratios of the spliced to the unspliced RNA molecules of the 19S family were measured. In the cytoplasm, unspliced 19S RNA represented between 1 and 2% of spliced 19S RNA. This ratio could be altered by the use of different methods of RNA extraction such that unspliced RNA was observed at 10 to 20% of spliced RNA. The nuclear ratios of spliced to unspliced 19S RNA were also determined. In contrast to cytoplasmic RNA, nuclear unspliced RNA was several hundred percent that of nuclear spliced 19S RNA. Cytoplasmic unspliced 19S RNA appears to be of nuclear origin, and its presence in the cytoplasmic fraction is due to nuclear leakage during RNA fractionation. PMID- 6253681 TI - Abrogation of radiation leukemia virus-induced lymphomagenesis by antisera to thymotropic but not to ecotropic or dual-tropic viruses. AB - Leukemia induction by culture-grown thymotropic radiation leukemia virus or by tumor-derived virus present in cell-free tumor extracts was abrogated by incubation of either virus with anti-thymotropoc virus serum, but not by antiserum raised against ecotropic or dual-tropic (mink cell focus-inducing type) viruses that were isolated from radiation leukemia virus-induced thymic leukemias. Thus, virus similar or identical to the cultured thymotropic leukemogenic species may also be the major biologically active principle in tumor derived extracts, even though the latter also contain viruses of the dual-tropic, mink cell focus-inducing type class. PMID- 6253682 TI - Construction of a specific amber codon in the simian virus 40 T-antigen gene by site-directed mutagenesis. AB - The site-directed bisulfite mutagenesis technique has been used to construct a specific mutation, am404, at nucleotide position 3124 in the simian virus 40 genome. The mutation was contained within a PstI restriction site (map position 0.27) and prevented cleavage by PstI at that position. Nucleotide sequence analysis of the mutagenized region indicated that only a single base pair change had occurred: a guanosine x cytosine leads to adenine x thymine transition. Comparison of the nucleotide sequence of am404 with the known DNA sequence of simian virus 40 indicted that the mutation in am404 resulted in the conversion of a glutamine codon to an amber codon. am404 could not replicate autonomously when transfected into monkey cells (BSC-40) but did replicate when it was cotransfected with the late deletion helper virus dl1007. On the basis of its position in the T-antigen, gene am404 should produce a T-antigen 24% shorter than the wild-type protein. PMID- 6253683 TI - Phosphorylation of the nonstructural proteins encoded by three avian acute leukemia viruses and by avian fujinami sarcoma virus. AB - The gag gene-related, nonstructural proteins of three avian acute leukemia viruses (namely, myelocytomatosis viruses MC29 and CMII and avian erythroblastosis virus) and of avian Fujinami sarcoma virus (FSV) isolated by immunoprecipitation from cellular lysates with anti-gag serum were shown to be phosphoproteins in vivo. The specific 32P radioactivity of the nonstructural proteins of MC29, CMII, and FSV was significantly higher than that of helper viral, intracellular gag proteins. Two of these proteins, i.e., the 140,000 dalton FSV and the 110,000-dalton MC29 proteins, were also phosphorylated in vitro by a kinase activity associated with immunocomplexes. This kinase activity is either separated from these proteins or inactivated by incubation of cellular lysates with normal serum followed by adsorption to staphylococcal protein A or sedimentation at 100,000 x g or both. It remains to be resolved whether the 110,000-dalton MC29 and 140,000-dalton FV proteins, in addition to being substrates for phosphorylation, also have intrinsic kinase activity. PMID- 6253685 TI - Enhancement and inhibition of CELO virus pathogenicity in quail by avian adenovirus-associated virus. AB - Dual infection of 12 day-old quail (Colinus virginianus) with 10(6) plaque forming units of CELO virus and low doses of avian adeno-associated virus (A-AV), resulted in significant enhancement of CELO virus-induced mortality, whereas dual infections with high doses of A-AV resulted in a delay in mortality. A-AV induced enhancement and inhibition of CELO virus pathogenicity could be blocked by the addition of A-AV antiserum prior to infection. PMID- 6253684 TI - Viruses isolated from cells persistently infected with vesicular stomatitis virus show altered interactions with defective interfering particles. AB - Virus mutants isolated from persistent infections of vesicular stomatitis virus in BHK-21 cells were much less susceptible to interference mediated by the defective interfering particle used to establish the persistent infection. This mutational change occurred as early as 34 days in the persistent infection and continued for over 5 years. The earliest variants showed no oligonucleotide map changes and no difference in the temperature-sensitive phenotype from the original virus, but the later variants exhibited extensive map changes. These results suggest a possible role for defective interfering particles in the selection of the mutants. PMID- 6253687 TI - Occurrence of pox in a northern fur seal on the Pribilof Islands in 1951. AB - The presence of pox in a northern fur seal pup, Callorhinus ursinus, examined at necropsy on the Pribilof Islands, Alaska, 13 September 1951 was confirmed by re examination of formalin-fixed tissues collected at that time. The disease was characterized by multiple 3 to 8 mm modules in the skin of the nose and flippers. Unlike pox lesions in other pinnipeds studied so far, the nodules were discrete dermal epitheliomas free of any direct connections with the overlying atrophic epidermis. They most likely arose from outer sheath cells of hair follicles. The tightly packed epithelial cells forming the nodules contained large, round, eosinophilic, intracytoplasmic inclusion bodies. As demonstrated by electron microscopy nearly 27 years after the tissues were fixed in formalin, poxvirus virions also were present in these cells. These findings indicate pox was present in a northern fur seal, hitherto undescribed in that species, 18 years before the disease was first reported in pinnipeds. PMID- 6253686 TI - An epornitic of avian pox in wild bobwhite quail. AB - An outbreak of avian pox, with an estimated 12-fold increase in the incidence of infection, occurred among wild bobwhites (Colinus virginianus) in the southwestern Georgia/northcentral Florida region. The outbreak was first detected in July, 1978, and continued at least until March, 1979. During this period, 26 separate clinical case accessions involving 43 bobwhites from 8 counties in Florida and Georgia were diagnosed as avian pox. A survey of 2,586 bobwhites from 6 southeastern states revealed avian pox infections in 312 bobwhites from Florida, Georgia, North Carolina, and Tennessee. Seventy-seven percent of the infected birds in the survey had only mild lesions on the legs and feet; however, 23% had more extensive lesions on the head. Severely affected birds had lesions around the eyes, nares, and in the mouth which impaired vision, respiration, and/or feeding. Infection rates were not related to age or sex of the birds but varied greatly among locales, even on adjoining properties. A morbidity rate of approximately 2% and a mortality rate between 0.6 and 1.2% were estimated for a 13,000 km2 region in Georgia and Florida. PMID- 6253688 TI - Oral antifungal agent effective even for widespread infections. PMID- 6253689 TI - Acyclovir for herpes: no clinical payoff yet. PMID- 6253690 TI - From the NIH: Human wart virus found in many papillomas. PMID- 6253691 TI - Brain metastases in small cell carcinoma. PMID- 6253693 TI - Subcutaneous crystal deposition in pseudogout. AB - Aspiration of inflamed periarticular tissues in seven patients suspected of having gout on clinical examination revealed positively birefringent calcium pyrophosphate crystals. The identification of calcium pyrophosphate crystals within articular structures and in the surrounding soft tissues and radiologic findings of chondrocalcinosis, in the absence of identifiable uric acid crystals, emphasize the importance of crystal identification in all cases of probable gout and stress the diagnostic role of soft-tissue aspiration in cases of soft-tissue inflammation, especially when arthrocentesis is unsuccessful. PMID- 6253694 TI - Microscopic aspects of receptor-mediated endocytosis. PMID- 6253692 TI - Spinal mineral loss in oophorectomized women. Determination by quantitative computed tomography. AB - Computed tomography (CT) provides precise anatomic localization coupled with quantitative x-ray attenuation information that can be used to determine bone mineral content. A precise and sensitive method for vertebral mineral measurement by CT is described and illustrated with results from an ongoing study of mineral loss in oophorectomized women. Spinal mineral loss measured by quantitative CT is compared with peripheral loss determined by photon absorptiometry and radiogrammetry. Vertebral cancellous bone loss was significant for the group as a whole at 12 months, while mean peripheral measurements showed no change. In two subjects in whom mineral change was significant at both sites, spinal loss was approximately five times greater than peripheral loss. PMID- 6253695 TI - Neuropathy after nitrous oxide abuse. PMID- 6253696 TI - Thyroid function after mantle irradiation in Hodgkin's disease. AB - We studied the thyroid function of 64 patients with Hodgkin's disease who received mantle irradiation during the period 1966 to 1976. More than two thirds (44 of 64) had some thyroid dysfunction. Twenty had mild dysfunction manifested by an abnormal thyroid-stimulating hormone response to thyrotropin-releasing hormone. Twenty had what could be termed compensated hypothyroidism while four were overtly hypothyroid. The severity of dysfunction was not related to age, sex, or chemotherapy. We found, however, that decreased thyroid function was inversely proportional to the length of time between a diagnostic lymphangiogram and the radiation therapy. These results are consistent with the hypothesis that the iodine load of the lymphangiogram renders the thyroid gland more radiosensitive. Thyroxine suppression of the thyroid gland during the period from the lymphangiogram through the termination of radiation therapy is suggested as a means of avoiding thyroid injury. PMID- 6253697 TI - Residual pathologic changes and 99mtechnetium pyrophosphate uptake following coxsackievirus B3 perimyocarditis in mice. AB - The myocardial uptake of technetium-99m pyrophosphate (99mTc-PYP) in perimyocarditis induced by coxsackievirus B3 in BALB/c mice was studied on 3rd- 90th day after the inoculation. 99mTc-PYP uptake ratio, measured by the ratio of cpm/gm for the heart to cpm/gm for the skull, began to increase five days after virus inoculation and reached a maximum on the seventh day. After the 14th day, 99mTc-PYP ratio began to decrease, however, on the 90th day, a high 99mTc-PYP uptake was shown in mice with severe perimyocardial fibrosis and calcification. The present findings may provide a futher basis upon which 99mTc-PYP imaging may be applied to viral perimyocarditis in humans. PMID- 6253698 TI - Experimental coxsackievirus B3 perimyocarditis in the right ventricle in BALB/c mice: a one-year follow-up study. AB - We described severe perimyocarditis in weanling BALB/c mice inoculated with coxsackievirus B3 (Nancy strain) which was exclusively limited to the right ventricle. Yellowish-white patches were seen on the surface of the right ventricle of the heart on the seventh day through 360th day after inoculation with virus. Following myocardial degeneration and necrosis, marked perimyocardial fibrosis with calcification was observed 90 days after inoculation with virus and persisted through 360th day. Spontaneous pericardial lesions were observed in the right ventricle in a few control mice, but these changes were different in severity and localization from perimyocarditis observed in mice infected with coxsackievirus B3. This animal model may provide an opportunity to study the natural course of perimyocarditis of viral etiology and possible sequel chronic or constrictive pericarditis in humans. PMID- 6253700 TI - [Experimental studies on administration method of chemotherapeutic agents. 16. Effect of polymyxin B against Pseudomonas aeruginosa (author's transl)]. AB - The most effective administration method of polymyxin B (PL-B), a peptide antibiotic, has been studied in the experimental mice infection with Pseudomonas aeruginosa. 1) Pseudomonas aeruginosa damaged by PL-B, when the drug was free, immediately began to regrow in vitro. 2) the therapeutic efficacy of PL-B on multiple administration was less effective than its single administration. 3) An important factor to decide the therapeutic efficacy of PL-B was the high drug concentration in plasma and peritoneal fluid. PMID- 6253699 TI - Peripheral effects of guanfacine compared to those of clonidine in the dog. AB - Comparative studies of the antihypertensive agents, guanfacine and clonidine, on their peripheral effects were performed using normotensive canine preparations. On the peripheral vascular beds, both drugs constricted cerebral renal and femoral vasculatures, but there were no decreases in the renal blood flow. This vasoconstriction was blocked by phentolamine, and guanfacine was about 3 times less potent than clonidine. Both drugs contracted the canine nictitating membrane, and had no effect on the ganglionic transmission in the cervical sympathetic ganglion. Qualitatively different effects were observed in their effects on renal function. Guanfacine slightly increased the urinary volume and Na excretion, while clonidine increased the urinary volume and K excretion. All these peripheral effects do not seem to be responsible for their hypotensive effect. PMID- 6253701 TI - Hepatic resections 1964-1979: vignettes drawn from the Malaysian experience. AB - We present a study of 288 hepatic resections carried out in Malaysia for the past fifteen years. First, we describe our indications for hepatic resectins which are not limited to hepatic trauma and hepatomas, but also include hepatic abscesses, cysts, intrahepatic calculi and hemangiomas. Second, we give a simplified classification of hepatic resections using accurate terminology. Third, we describe the safety of hepatic resections in our hands which we believe is due to specially designed surgical instruments and the accurate decision making process at surgery. We have had minimum postoperative mortality and no intraoperative deaths so far. Finally, while analysing each indication we have drawn vignettes from our experience for the past fifteen years. PMID- 6253702 TI - [Endocrinological studies on pathogenesis of urolithiasis. I. Characteristics of cyclic AMP (author's transl)]. PMID- 6253703 TI - [Endocrinological studies on pathogenesis of urolithiasis. II. Cyclic AMP as an index of parathyroid function in primary hyperparathyroidism (author's transl)]. PMID- 6253704 TI - [Two cases of congenital mesoblastic nephroma (author's transl)]. PMID- 6253705 TI - Levels of cyclic nucleotides in autotransplanted 7, 12-dimethylbenz[a]anthracene induced rat mammary tumors during their growth and regression. AB - Previous studies indicated that autotransplanted 7, 12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary tumors were hormone-dependent and, if derived from a single primary tumor, many of their metabolic parameters varied little. Therefore, these tumors transplanted in multiple sites provided an opportunity for serial sampling of individual tumors for repeated biochemical evaluations. In the present study, primary mammary tumors induced by DMBA in female noninbred Sprague-Dawley rats were autotransplanted at six sites. When these grafts grew to an average size of 6 cm, the hosts were ovariectomized. Eighteen days later when all tumors were apparently regressing, a silastic tubing 2 cm long containing crystalline estradiol was implanted sc into each host for 14 days. Individual tumors were serially removed from each host before ovariectomy, after ovariectomy, and after estrogen replacement. Levels of cyclic AMP (cAMP) and cyclic GMP (cGMP) in these tumors were measured by radioimmunoassay. Results indicated that tumor regression was associated with an elevation of cAMP levels and that tumor growth was accompanied by a decline in cAMP. The level of cGMP did not correlate with either tumor growth or regression. Therefore, the concept that cAMP is a biologic regulator for tissue proliferation and regression may be applied to the present model of autotransplanted, DMBA-induced rat mammary tumors. PMID- 6253706 TI - Serial cytogenetic studies of nonendemic Burkitt's lymphoma cell lines. AB - Cytogenetic study of nonendemic Burkitt's lymphoma (BL) cell lines showed a translocation of chromosomes #8 and #14, t(8;14), present in 16 of the 18 lines examined. Serial cytogenetic studies of nine of these lines showed the t(8;14) to be stable and present in all cells examined. Although many other chromosome aberrations were present, they did not demonstrate the stability or the pervasiveness of the t(8;14). The significance of these results and previously reported cytogenetic studies on the etiology of BL was discussed. PMID- 6253707 TI - Serum levels of fibronectin and a fibronectin-like DNA-binding protein in patients with various diseases. AB - The levels of fibronectin and the fibronectin-like, malignant disease-associated DNA-binding protein (MAD-2) were determined in sera from patients with various diseases. The levels of both proteins were elevated in most serum samples from patients with various types of cancer and in some patients with nonmalignant diseases. The highest levels of these proteins were found in patients with carcinomas of the breast and lung. A subset of the lung cancer patients with small cell carcinoma had either normal or depressed marker levels. The levels of fibronectin and MAD-2 varied concordantly in the different patient populations studied, which suggests that the serum levels of the fragment are directly proportional to the total amount of fibronectin in the serum. PMID- 6253708 TI - Systemic and in situ natural killer activity in C57BL/6N and CBA/N mice bearing murine sarcoma virus-induced regressor tumors. AB - Both systemic and in situ natural killer (NK) activity was assessed in young and old C57BL/6N and CBA/N mice bearing primary murine sarcoma virus-induced tumors. Splenic NK activity was depressed in tumor-bearing mice relative to normal age matched controls. In situ NK activity was detected in young mice, and the level paralleled that found in the spleens of the same mice. In older mice, in situ NK activity was not detected. Furthermore, the depressed levels of activity in the spleens of tumor-bearing mice seemed to reflect systemic effects rather than migration of NK cells from the spleen to the tumor site. PMID- 6253709 TI - Glycosphingolipids of metastatic variant RNA virus-transformed nonproducer Balb/3T3 cell lines: altered metabolism and cell surface exposure. PMID- 6253710 TI - Reevaluation of the effect of mouse mammary tumor virus infection on the BALB/c mouse hyperplastic outgrowth. AB - The BALB/c (C-) mouse hyperplastic outgrowth line (D1) was used to study murine mammary tumor virus (MuMTV) expression in both D1 and tumors derived from D1. D1 was transplanted into virus-infected BALB/cfC3H (C+) and virus-uninfected C- animals. In duplicate studies, tumor incidence was the same in both groups. However, the tumor latency period was longer for D1 transplanted into C+ mice (D1/C+) than for D1 transplanted into C- mice (D1/C-). MuMTV was detected in 85% of D1/C+ outgrowths and in 29% of D1/C+ tumors but was never detected in D1/C- outgrowths or tumors. D1/C- outgrowth and tumors and most of the D1/C+ tissues expressed little or no MuMTV RNA. Some D1/C+ tumors expressed substantial levels of MuMTV RNA. These same tumors also had MuMTV antigen and contained the exogenously acquired C3H-MuMTV provirus in the cellular DNA as shown by DNA fragment patterns following cleavage with Pst I and Eco RI endonucleases. D1/C+ tumors containing no viral RNA were also antigen-negative and lacked the acquired C3H provirus. These studies indicate that D1 has substantially changed in its incidence and in its response to MuMTV. MuMTV infection was not tumorigenic in the traditional sense, a finding that has led to a reevaluation of our current models of virus-host relationships and the biology of precancerous conditions. PMID- 6253711 TI - Influence of histologic subtype of small cell carcinoma of the lung on clinical presentation, response to therapy, and survival. AB - Patients with small cell carcinoma of the lung (SCCL) were histologically subtyped according to the Working Party for Therapy of Lung Cancer classification and were treated with combination chemotherapy. Of the 103 patients studied, 54 had the lymphocyte-like (oat cell) subtype, 41 had the intermediate cell subtype, and 8 had a mixture of the two. No significant difference in initial performance status, extent of disease, chemotherapeutic response rate, or survival (median, 10.2 mo) was noted among the histologic subtypes. When the histologic subtype of the primary biopsy tissue was compared with the subtype of other pathology specimens from the same patient, concordance of subtype was present in 74% of the patients. In the remaining 26%, two or three histologic subtypes were present. This study demonstrates no clinically significant differences among the various histologic subtypes of SCCL in patients extensively staged and treated with aggressive cytotoxic therapy. Because of this and because concurrent biopsy tissues from multiple sites in the same patient may vary in subtype, we conclude that prognostic or therapeutic decisions should not be based on SCCL subtype. PMID- 6253712 TI - Regulation of methionine adenosyltransferase in normal diploid and simian virus 40-transformed human fibroblasts. AB - Methionine adenosyltransferase activity in normal diploid and simian virus 40 (SV40)-transformed human fibroblasts increased severalfold when cell monolayers were cultured in medium deficient in L-methionine. This increase in methionine adenosyltransferase activity required RNA and protein syntheses and probably represented a derepression of the enzyme's biosynthesis. Furthermore, studies with RNA synthesis inhibitors suggested that the regulation of this enzyme activity in human fibroblasts involved posttranscriptional mechanisms. The inclusion of homocysteine thiolactone, a metabolic precursor of methionine, in the methionine-deficient medium inhibited the derepression in normal human fibroblasts but augmented the derepression in fully transformed fibroblasts. These differences in derepression patterns thus appeared related to altered metabolism of homocysteine and/or methionine in SV40-transformed human fibroblasts and as such may serve as a transformation marker in SV40-transformed cells. PMID- 6253713 TI - Nucleolar ultrastructure and transcription of preribosomal RNA in Rous sarcoma virus-transformed chick embryo fibroblasts treated with alpha-amanitin. AB - Uninfected and Rous sarcoma virus (RSV)-transformed chick embryo fibroblasts (CEF) were exposed to various concentrations of alpha-amanitin for different lengths of time. At a concentration of 4 micrograms alpha-amanitin/ml, RSV transformed cells were shown to maintain a normal rate of transcription of all classes of RNA, whereas in uninfected cells transcription was reduced to a very low level. These observations cannot be accounted for by a difference in the penetration rate of alpha-amanitin through the plasma membrane. Investigation of the ultrastructure showed that the degree of nucleolar fragmentation induced by alpha-amanitin was comparable in both types of cells. Persistence of transcription with concomitant nucleolar fragmentation in alpha-amanitin-treated RSV-transformed CEF is not in accord with the hypothesis that nucleolar integrity is required for preribosomal RNA transcription. PMID- 6253714 TI - Protection of cats against progressive fibrosarcomas and persistent leukemia virus infection by vaccination with feline leukemia cells. AB - Young cats (3-6 mo old) were challenged with oncogenic Snyder-Theilen feline sarcoma virus (FeSV) after vaccination with live or killed FL74 cat lymphoma cells. Compared with controls immunized with normal cat fibroblasts, the FL74 vaccinated cats exhibited increased resistance to FeSV-induced progressive primary and disseminated secondary tumors. Maximum protection was achieved by vaccination with live FL74 cells or with a low dose of freeze-thawed cells, but tumor cells inactivated by glutaraldehyde or paraformaldehyde were also effective. Infectious helper feline leukemia virus (FeLV) was detected in the blood of all cats after FeSV challenge, but the duration and magnitude of this viremia were reduced in animals that had been previously vaccinated with live, freeze-thawed, or paraformaldehyde-fixed cells. Although immunized cats were resistant to FeSV-induced tumors and FeLV viremia, no evidence was obtained to suggest that vaccination with dead cells induced detectable circulating antibody prior to challenge with oncogenic virus. After FeSV challenge, complement dependent antibody to feline oncornavirus-associated cell membrane antigen (CDA FOCMA) appeared at high titer in cats that were destined either to survive tumor free or to develop small, localized, and eventually regressing tumors. Cats immunized with live FL74 cells developed CDA-FOCMA prior to challenge, and antibody appeared in these cats following an episode of transient FeLV viremia induced by virus replicating from the injected tumor cells. Therefore, apparently, a state of transient or persistent FeLV viremia regularly preceded detection of CDA-FOCMA activity. Several individually derived feline lymphoma cell lines were used as targets for CDA-FOCMA, and the results suggested that lytic activity is directed to multiple antigen determinants expressed differently by individual feline lymphomas. PMID- 6253715 TI - [Anticonvulsants and their side effects. II. Side effects]. PMID- 6253716 TI - [Multiple primary cancer of the esophagus and lung]. PMID- 6253717 TI - [Malignant synovioma]. PMID- 6253718 TI - [Diagnosis and treatment of cancer of the large intestine]. PMID- 6253719 TI - [Surgical treatment of complicated forms of colonic cancer]. PMID- 6253720 TI - [Sarcoma of both breasts]. PMID- 6253721 TI - [When should metastases be operated in children with malignant tumours? (author's transl)]. PMID- 6253722 TI - [Treatment and prognosis of Wilms' tumor. Analysis of 30 patients (author's transl)]. AB - The extraordinary results of treatment of Wilms' Tumor has made it a model for interdisciplinary treatment of malignancies in children. Grouping by pathological and clinical findings helps to estimate the prognosis and to establish an individual therapeutic protocol. Since 1972 the overall 5 years survival rate of our patients (n = 30) is 86%. PMID- 6253723 TI - [Diagnosis of inflammatory diseases of the CNS in children by means of CSF protein electrophoresis (author's transl)]. PMID- 6253724 TI - Non-functioning islet cell carcinoma difficult to differentiate from duodenal carcinoma--a case report. PMID- 6253725 TI - The effect of 4-aminopyridine on the nicotinic transmission of bullfrog sympathetic ganglion cells. PMID- 6253727 TI - [Alternative medicine]. PMID- 6253726 TI - A simple and rapid assay for collagenase activity using fluorescence-labeled substrate. PMID- 6253728 TI - [Traditional Chinese medicine]. PMID- 6253729 TI - [Reflexology and nursing care]. PMID- 6253730 TI - [Shiatsu massage and reflexology in nursing practice]. PMID- 6253732 TI - [Medical sophrology]. PMID- 6253731 TI - [What is homeopathy?]. PMID- 6253733 TI - [Sophrology and nursing care]. PMID- 6253734 TI - [A nurse at the 4th World Congress of Natural Medicine, Geneva 29 to 31 May 1980. Current fashion of new roads?]. PMID- 6253735 TI - [Magnetism. Experience in "natural" medicine: another dimension in the helping relationship]. PMID- 6253736 TI - [The pill and smoking]. PMID- 6253738 TI - [The development of the Swiss hospital system]. PMID- 6253737 TI - [75 years since the birth of Le Bon Secours... 1905-1980]. PMID- 6253739 TI - [Schizophrenia: pathology and therapy of schizophrenic persons]. PMID- 6253740 TI - [Establishment of the Alumnae Association of the Cadre School for Nursing of the Swiss Red Cross]. PMID- 6253741 TI - [Study of a description of hospital personnel supply in Switzerland]. PMID- 6253742 TI - Performance of 3 successive generations of specified-pathogenfree chickens maintained as a closed flock. AB - No antibodies against Salmonella pullorum, Mycoplasma gallisepticum, Mycoplasma synoviae, Haemophilus gallinarum, fowl pox virus, Marek's disease virus, herpes virus of turkey, infectious laryngotracheitis virus, avian adenovirus, avian reovirus, infectious bursal disease virus, reticuloendotheliosis virus, avian leukosis virus, avian encephalomyelitis virus and Newcastle disease virus were detectable in the sera obtained from these chickens in 3 generations at various ages. Antibodies against infectious bronchitis virus were detected in the sera of the 3rd generations at 66, 74 and 108 weeks of age. The performances of these chickens was nearly the same as that of conventional healthy chickens in the poultry industry, with no tendency to decline. PMID- 6253743 TI - Isolation and characterization of a cytomegalovirus from the salivary gland of a squirrel monkey (Saimiri sciureus). PMID- 6253744 TI - Hepatitis A and B: serologic survey of human and nonhuman primate sera. AB - Sera of humans and seven species of nonhuman primates were tested by radioimmunoassay and enzyme immunoassay for the presence of hepatitis A antibody, hepatitis B surface antigen and antibody to hepatitis B surface antigen. The outcome of testing a total of 276 serum or plasma specimens was as follows: with the exception of squirrel monkeys (0%) and cotton-top marmosets (0%), a considerable percentage of all other species tested had detectable antibodies to hepatitis A virus: humans 45.9%, chimpanzees 36.6%, baboons 38.2%, vervets 57.9%, cebus monkeys 40.0% and common marmosets 50.0%. Only one human and two chimpanzees were carriers of hepatitis B surface antigen. Antibodies to hepatitis B surface antigen were detected in human (11.3%), chimpanzees (29.9%), baboons (36.2%) and squirrel monkeys (5%). Chimpanzees showed an increasing prevalence of antibodies to hepatitis A virus and hepatitis B surface antigen with age. PMID- 6253746 TI - Virus associated papillomas in colobus monkeys (Colobus guereza). AB - Numerous papillomas ranging in size from 1--10 mm were seen in four colobus monkeys (Colobus guereza). The lesions were confined to the fingers and toes and to the dorsal-lateral aspects of the hands and feet distal to the carpus and tarsus. Electron microscopy of two of the lesions revealed compactly arranged crystalline arrays of intranuclear virus particles in the epidermis. The particles were seen only in cells of the stratum granulosum and stratum corneum. By the negative stain technique, the non-enveloped spherical particles measured 52--58 mm in diameter. The arrangement of the capsomeres was consistent with an icosahedral symmetry. The observations suggested a viral etiology for the cutaneous papillomas similar to that of other mammalian species. PMID- 6253745 TI - Detection of antibody titers to bovine viruses in rabbit sera. AB - Sera obtained from 30 New Zealand white rabbits from four different colonies were evaluated for the presence of immunoglobulins to 10 bovine viruses. Serum neutralizing antibody titers to bovine adenovirus Type 1 and to the enteroviruses Types 3 and 4 were detected. PMID- 6253748 TI - Serum angiotensin converting enzyme in patients with Crohn's disease. PMID- 6253747 TI - Natural genital herpesvirus hominis infection in chimpanzees (Pan troglodytes and Pan paniscus). AB - Type 2 Herpesvirus hominis was isolated from pustulovesicular lesions on the external genitalia of two chimpanzees. Histopathologic examination of biopsy specimens from both animals revealed typical herpetic changes which included necrosis, superficial ulceration acute inflammatory cell infiltration, multinucleated syncytial giant cells, and intranuclear inclusions. Large numbers of herpes-type viruses were demonstrated by electron microscopy in biopsy specimens from both animals. Serologic studies also demonstrated infection of these animals with Herpesvirus hominis. PMID- 6253749 TI - Three dimensional structure and sequence homology determine splicing sites in eukaryotic precursor RNA. PMID- 6253750 TI - Ascorbate, cyclic nucleotides, citrus and a model for preventing large bowel cancer. PMID- 6253751 TI - Transbronchoscopic versus surgical resection of tracheobronchial granular cell myoblastomas. Suggested approach based on follow-up of all treated cases. AB - The case of a 31-year-old patient with a granular cell myoblastoma causing significant obstruction of the distal trachea is presented. A review of the literature suggests that size may help in deciding whether bronchoscopic removal or surgical resection should be performed. Fifty-four percent of the tumors removed bronchoscopically whose follow-up was described showed recurrent disease. All tumors removed bronchoscopically whose diameter was 1 cm or greater recurred. The correlation of full-thickness involvement of the tracheal wall with increasing tumor size appears to explain the failure of bronchoscopic treatment of these tumors. A suggested surgical approach to these rare tumors is proposed. PMID- 6253752 TI - Initial uptake and insulin releasing action of chloromercuribenzene-p-sulphonic acid (CMBS) in suspensions of pancreatic islet cells. AB - The effects of chloromercuribenzene-p-sulphonic acid on dispersed cells prepared from beta-cell-rich ob/ob-mouse islets were studied. 1) Chloromercuribenzene-p sulphonic acid at concentrations of 0.1 mmol/l or higher diminished cell viability which was partially counteracted by increasing concentrations of bovine serum albumin. 2) The uptake of 203Hg-chloromercuribenzene-p-sulphonic acid after incubation for 4 seconds or longer showed that most of the non-toxic concentrations of chloromercuribenzene-p-sulphonic acid was bound to the cell within 40 seconds. Maximal uptake was achieved after 3 minutes of incubation. The uptake of radioactive chloromercuribenzene-p-sulphonic acid was inhibited by bovine serum albumin. 3) The dynamics of insulin release from perifused dispersed beta-cells embedded in fibrin showed a maximal 40--50-fold stimulation by 0.03 mmol/l chloromercuribenzene-p-sulphonic acid within 10 minutes of perifusion. 4) Scanning electron microscopy of beta-cells revealed no major changes in the cell surface under conditions of maximal binding and insulin releasing effects of chloromercuribenzene-p-sulphonic acid. These data support the concept that the ability of chloromercuribenzene-p-sulphonic acid to induce insulin release is related to its initial binding to the beta-cell surface. The binding of chloromercuribenzene-p-sulphonic acid and the subsequent release of insulin seem to occur without major changes in beta-cell surface morphology. PMID- 6253754 TI - Do endogenous prostaglandins modulate noradrenergic transmission in the rat isolated perfused vas deferens? AB - The effects of the prostaglandin synthetase inhibitors aspirin, indomethacin and meclofenamic acid have been studied on the response of the rat isolated perfused vas deferens. None of these drugs, up to a concentration of 5 x 10(-5) M affected either phase of the biphasic constrictor response to 30 s periods of field stimulation. In the same preparations an inhibition of the response to field stimulation was seen in the presence of prostaglandin E1 at concentrations of 1 to 5 ng ml-1. All three prostaglandin synthetase inhibitors, at 5 x 10(-5) M, caused significant reduction of prostaglandin biosynthesis by homogenates of rat vas deferens. It is, therefore, suggested that stimuli which activate directly the noradrenergic nerves in the rat vas do not activate simultaneously a release of endogenous prostaglandins. PMID- 6253753 TI - Immunopharmacology: regulation of precursor cells. AB - A new area of immunopharmacology is described which deals with the regulation of the neogenesis of blood-forming cells. Hemo/immunopoiesis is the process which describes the differentiative and proliferative status of cells as they progress from the most primitive pluripotent stem cell to the most mature functional end stage cells (erythrocytes, myeloid cells and lymphocytes). This so-called "hemic cell renewal" system is under intricate control mechanisms which can be modulated by the "hemopoietic-inductive microenvironment", cell-cell interactions, hemopoietins, cyclic nucleotides, calcium, prostaglandins and pharmacological agents. Hopefully, the interesting findings that have occurred in this area of research over the past decade can be translated into useful clinical modalities for the treatment of hematological and immunological disorders. PMID- 6253755 TI - [Treatment of functional colonic diseases and colonic diverticulosis. Comparative effects of bran and Kaologeais using a crossover method]. PMID- 6253756 TI - [Tetracosactide in the acute phase of cerebrovascular accidents]. PMID- 6253757 TI - Induction of ornithine decarboxylase in macrophages by bacterial lipopolysaccharides (LPS) and mycobacterial cell wall material. PMID- 6253758 TI - Hypoxia and cold: influence on cellular oxygen consuming systems in guinea pig liver. PMID- 6253760 TI - Benzodiazepine receptor loss in brains of mice after chronic alcohol consumption. PMID- 6253761 TI - [Fraud in medicine from the viewpoint of the jurist]. PMID- 6253759 TI - Bremazocine: a potent, long-acting opiate kappa-agonist. PMID- 6253762 TI - [Infection of New World primates by Junin virus. II Callithrix jacchus]. PMID- 6253763 TI - [Effect of cyclophosphamide and antithymocyte serum on the resistance of the adult rat to Junin virus]. PMID- 6253764 TI - [Preliminary study of an atenuated variant of Junin virus derived from the XJ prototype strain]. PMID- 6253765 TI - [Viral etiology of breast cancer]. PMID- 6253766 TI - H + -substrate cotransport by the melibiose membrane carrier in Escherichia coli. AB - Proton entry into anaerobic Escherichia coli in response to the addition of HCl was measured by monitoring pH changes in the external solution. Preincubation of cells in a Na+ -free medium containing melibiose or methyl-alpha-galactoside (alpha MG) stimulated the rate of H+ entry in response to the acid pulse. This melibiose- or alpha MG-dependent proton pathway appeared to be identical to the melibiose carrier, since the channel was only observed in melibiose-induced cells. Furthermore, this membrane pathway for protons showed the same temperature sensitivity as the melibiose carrier (active at 30 degrees but inactive at 37 degrees). These observations are consistent with the idea that the melibiose transport system provides a pathway for protons in the presence of appropriate substrates, but that the pathway is closed to protons in the absence of the sugar. Such observations indicate that there is an obligatory coupling between H+ flux and melibiose or alpha MG flux through the carrier when Na+ is omitted from the incubation medium. PMID- 6253769 TI - Concanavalin A agglutinability of some enveloped RNA viruses modified by host cell transformation. AB - The dependence on concanavalin A (Con A) concentration of agglutinability of some enveloped RNA viruses grown in transformed cells was compared with that of those grown in nontransformed cells. The avian oncoviruses were purified by centrifuging to equilibrium in a combination equilibrium: viscosity gradient of potassium tartrate and glycerol after conventional isopycnic sucrose density gradient centrifugation. Avian oncoviruses were more agglutinable with Con A when grown in transformed cells than when grown in nontransformed cells. Vesicular stomatitis virus grown in transformed cells was also more agglutinable than the virus grown in nontransformed cells. These results agree with the concept that the envelopes are modified by host cell transformation and that, therefore, viruses grown in transformed cells are expected to be more agglutinable with Con A than those grown in nontransformed cell. PMID- 6253768 TI - Basal lamina thickness permeability to horseradish peroxidase of intraneural capillaries in diabetic mice. PMID- 6253767 TI - Lack of adenosine-3',5'-monophosphate receptor protein and apparent lack of expression of adenosine-3',5'-monophosphate functions in Mycobacterium smegmatis CDC 46. AB - The presence of adenosine-3',5'-monophosphate (cAMP), adenylate cyclase and the effect of glucose on cAMP levels in Mycobacterium spp have been reported earlier. To understand the role(s) of cAMP in these organisms, the induction of various enzyme systems was studied. Beta-galactosidase and L-tryptophanase were present at low levels of activity and could not be induced. Glycerokinase was inducible but the induction was not affected by glucose. The fructose uptake system was inducible, and the induction was lowered in the presence of glucose, but cAMP could not reverse the inhibition. cAMP binding protein was not detectable under a variety of conditions. On the basis of the lack of active cAMP binding protein, a model has been proposed to explain the apparent lack of expression of cAMP function in Mycobacterium smegmatis CDC 46. PMID- 6253770 TI - Superoxide anion-generating activities of macrophages as studied by using cytochalasin E and lectins as synergistic stimulants for superoxide release. AB - Treatment of macrophages with cytochalasin E in combination with a lectin was found to stimulate the generation of superoxide anions (O2-) very efficiently. The macrophages stimulated with concanavalin A, phytohemagglutinin or wheat germ agglutinin released superoxide, but cells pretreated with cytochalasin E released much greater amounts of superoxide, without notable lag time, upon stimulation with the lectin. Wheat germ agglutinin was found to be the most efficient stimulant among the lectins tested. Superoxide generation in guinea pig macrophages was shown to be dependent largely on cytoplasmic glucose metabolism and to some extent on mitochondrial respiration, since the superoxide release was largely but not totally inhibited by 2-deoxyglucose and to a lesser extent by antimycin A or KCN. The method presented is sensitive and allows rapid assay of the superoxide-generating activity with only 1--5 X 10(5) macrophages for a single determination. In application of this technique, elevation of the superoxide-generating activity was shown with macrophages elicited by chemical inflammation or those obtained from mice after treatment with tubercle bacilli. PMID- 6253771 TI - Cell differentiation, aging and cancer: the possible roles of superoxide and superoxide dismutases. AB - A unified theory of cell differentiation, aging, and cancer is discussed. All cells are hypothesized to originate from stem cells. These stem cells mature as they divide and eventually reach a fully differentiated cell, which cannot divide. Aging is caused by the loss of stem cells, either due to cell death or terminal differentiation, and by eventual death of fully differentiated cells. Both loss of stem cells and death are brought about by oxygen radicals. The cancer phenotype is caused by an inability of a stem cell to differentiate fully under the local environmental conditions. Because the cancer cell cannot differentiate, it never loses its potential for growth. The block in differentiation of cancer cells is caused by a relative lack of radical scavengers, particularly manganese superoxide dismutase, coupled with production of radicals, especially superoxide. The high reactivity of these radicals leads to changes in key subcellular structures and prevents the cell from attaining the organization needed for cell differentiation to occur. PMID- 6253772 TI - Interactions between zinc, essential fatty acids and prostaglandins: relevance to acrodermatitis enteropathica, total parenteral nutrition, the glucagonoma syndrome, diabetes, anorexia nervosa and sickle cell anaemia. AB - Many of the features of zinc deficiency and of essential fatty acid (EFA) deficiency are similar in both animals and humans. The two agents interact in various ways. EFAs are important in zinc absorption, probably after conversion to prostaglandins (PGs). Zinc seems necessary for at least two stages in EFA metabolism, the conversion of linoleic acid to gamma-linolenic acid, and the mobilisation of dihomogammalinolenic acid (DGLA) for the synthesis of 1 series PGs. Zinc may also be important in the conversion of DGLA to arachidonic acid and in arachidonic acid mobilisation for 2 series PG formation. These interactions shed considerable light on a number of clinical syndromes, including acrodermatitis enteropathica, total parenteral nutrition, diabetes mellitus, the glucagonoma syndrome and sickle cell anaemia. There is substantial evidence to suggest that anorexia nervosa is due to a combined deficiency of zinc and EFAs. Understanding of the roles of zinc and EFAs in these various clinical situations is likely to lead to improved therapy. PMID- 6253774 TI - Is the action of peptide hormones of gastrointestinal origin on the hypothalamic satiety center modulated by REM sleep-dependent release of their central nervous analogues? PMID- 6253773 TI - A biochemical basis for alcoholism and alcohol-induced damage including the fetal alcohol syndrome and cirrhosis: interference with essential fatty acid and prostaglandin metabolism. AB - Alcohol has at least two actions on essential fatty acid (EFA) and Prostaglandin (PG) metabolism. It enhances the conversion of dihomogammalinolenic acid (DGLA) to PGE1 but it blocks the activity of the delta-6-desaturase, an enzyme necessary for replenishment of DGLA stores from dietary precursors. The acute effect of ethanol is therefore an increased production of PGE1 but chronic consumption will lead to depletion of DGLA and PGE1. Withdrawal from alcohol will lead to a precipitous fall in PGE1. PGE1 is known to have profound effects on the nervous system and behaviour. Patients with mania produce more PGE1 than normal while those with depression make less. Alcoholics may drink to maintain a normal PGE1 level, something which will require more and more ethanol as DGLA is depleted. In both animals and humans PGE1 or its precursor, gamma-linolenic acid (GLA) have been shown to attenuate the acute withdrawal syndrome. PGE1 injections prevent the development of fatty liver in alcohol-treated animals. Defective EFA and PGE1 metabolism are known to lead to increased fibrosis, reproductive failure, cardiomyopathy, cardiovascular disorders, gastritis and pancreatitis and could therefore be the basis for these disorders in alcoholics. A PGE1 deficiency could also be responsible for the fetal alcohol syndrome. Three other agents are known to produce constellations of fetal defects very similar to those found in the alcohol syndrome. These other factors are dihphenylhydantoin, lithium, and a deficiency of zinc. These three factors and excessive alcohol consumption all lead to PGE1 deficiency by different routes. If this concept is correct, the key to the management of alcoholism and its medical complications lies in the provision of GLA or DGLA, fatty acids which by-pass the alcohol blocked step and which are unfortunately unlikely to be present in any normal diet. Unlike many concepts of alcoholism and alcohol damage, the EFA/PGE1 idea is very readily testable and already has considerable experimental support. PMID- 6253775 TI - Guar in management of diabetes. PMID- 6253776 TI - Herpes virus in an obstetric hospital. II: Asymptomatic virus excretion in staff members. AB - Serial studies of specimens of saliva from 384 asymptomatic members of staff of an obstetric hospital resulted in the isolation of herpes simplex virus (HSV) from 9.6%. This exposure rate of patients to HSV infection was contrasted with the very low incidence of HSV infection in neonates in Australia. Factors associated with the incidence of overt HSV infection and intermittent asymptomatic excretion of HSV were noted and assessed in relation to possible sites of virus location. PMID- 6253777 TI - Multiple myeloma with bilateral orbital infiltration and polyneuropathy. AB - Orbital involvement is a rare complication of myeloma usually presenting as unilateral proptosis without pain. A case is reported of a woman with bilateral orbital infiltration without proptosis, who became blind within three months of the onset diplopia. The blindness was due to visual field obstruction, with eyelids covering both corneas; the eyes themselves remained normal. This is the first case of orbital myeloma reported in Australia and only the second case of bilateral primary orbital infiltration with myelomatosis to be reported in the world literature. PMID- 6253778 TI - [Extended ACTH rapid test for differentiation of primary and secondary adrenal insufficiency]. AB - In 30 resting normal persons, 5 ambulant normal persons and 3 patients with disorders of the pituitary-adrenal-system before and 30 minutes after intravenous injection of 0,25 mg synthetic adrenocorticotrophin (tetracosactid, Synacthen) plasma cortisol and aldosterone levels were evaluated. The evaluation of the corticoids was continued over 240 minutes in intervals of 30 minutes. The basal cortisol and aldosterone levels of the resting normal persons and ambulant persons ordinarily doubled 30 minutes after ACTH application. The plasma cortisol level of a steroid-treated patient with lupus erythematodes disseminatus rose subnormally but his aldosterone level increased normally. 2 patients with untreated hypopituitarism had subnormal plasma cortisol and normal aldosterone responses after ACTH administration. In contrast with patients with primary adrenal insufficiency, whose plasma aldosterone levels fail to rise, patients with secondary adrenal insufficiency had normal corticotrophin-stimulated aldosterone increments. Thus the extended ACTH test can be useful in differential diagnosis of primary and secondary adrenal insufficiency. PMID- 6253780 TI - Bovine lymphosarcoma. PMID- 6253779 TI - [A case of fibroangioma of the spermatic cord]. PMID- 6253781 TI - Myoblastoma. Equine granular cell tumor. AB - A unilateral pulmonary granular cell tumor occurred in a Thoroughbred mare with longstanding respiratory disease wrongly attributed to chronic obstructive pulmonary disease. The clinical features, radiology and endoscopic appearance permitted an accurate diagnosis, which was supported by subsequent necropsy and histologic examination. Obstructive pulmonary disease was ruled out after measurement of arterial blood gases and maximum intrathoracic pressure changes, and after microscopic examination of the lung. PMID- 6253783 TI - [Methods of medical outsiders from the lawyer's point of view (author's transl)]. AB - As a consequence of the widespread humbug in Medicine today the number of law suits against medical outsiders causing damage to patients is visibly increasing. Quackery is unmasked by typical features common to nearly all occult sciences. In cases of failure or doing harm to patients medical outsiders have to face indictment more than scientifically treating physicians. Sometimes there is even suspicion of deliberate cheating, if not mental disorder. Legislation is urged to bring to an end this humiliating form of quackery. PMID- 6253782 TI - [Paramedicine (author's transl)]. PMID- 6253784 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 48-1980. PMID- 6253785 TI - Biochemical evaluation of patients with cancer-associated hypercalcemia: evidence for humoral and nonhumoral groups. AB - In 50 consecutive patients with cancer-associated hypercalcemia, we measured nephrogenous cyclic AMP, tubular phosphorus threshold, fasting calcium excretion, plasma 1,25-dihydroxyvitamin D, and immunoreactive parathyroid hormone as determined by four region-specific antiserums. Nephrogenous cyclic AMP excretion was elevated in 41 patients and suppressed in nine (means, 5.85 vs. 0.51 nmol per 100 ml of glomerular filtrate). There was no overlap between these groups. When compared with 15 patients with primary hyperparathyroidism, the group with increased cyclic AMP excretion had similar reductions in tubular phosphorus threshold; higher fasting calcium excretion (means, 0.66 vs. 0.25 mg per 100 ml of glomerular filtrate, P < 0.01); marked reductions in 1,25-dihydroxyvitamin D (means, 20 vs. 83 pg per milliliter, P < 0.001); and lower levels of immunoreactive parathyroid hormone in all four assays. The data suggest that elevated excretion of nephrogenous cyclic AMP may be a useful marker of humorally mediated cancer-associated hypercalcemia, that this type of hypercalcemia is common, that the humoral factor responsible for this syndrome is not native 1-84 parathyroid hormone, and that the various subtypes of cancer-associated hypercalcemia are biochemically distinguishable from primary hyperparathyroidism. PMID- 6253786 TI - A new genetic basis for hemoglobin-H disease. AB - We studied 11 families with alpha-thalassemia from the Qatif population of eastern Saudi Arabia to determine the genetic and molecular basis of hemoglobin-H disease, which is being encountered in this area with increasing frequency. The results show that there are two common alpha-thalassemia haplotypes, a deletion ( alpha/) determinant and a nondeletion (alpha alpha T/) determinant, which interact to produce a series of overlapping phenotypes. The most severe, hemoglobin-H disease, results from the homozygous state for the nondeletion determinant--a pattern of inheritance not previously recognized for this condition. Its molecular and genetic properties are thus different from those that produce the condition in Oriental or Mediterranean populations. PMID- 6253788 TI - Glycosylated hemoglobin (HbA1) in a case of insulinoma. PMID- 6253787 TI - The multiple causes of hypercalcemia in malignant disease. PMID- 6253789 TI - Intraoperative measurements of urinary cyclic AMP to guide surgery for primary hyperparathyroidism. PMID- 6253790 TI - Pulmonary fibrosis and angiotensin I-converting enzyme. PMID- 6253791 TI - Epstein--Barr virus-induced cell fusion. AB - Serological and molecular biological studies have shown an association between Epstein--Barr virus (EBV) and nasopharyngeal carcinoma. Although it has been shown that the epithelioid tumour cells carry EBV genomes, they are apparently devoid of receptors for EBV (H.W., unpublished observations). Other have suggested that fusion of EBV carrying cells with epithelial cells may be the mode of entry of the virus into cells unable to absorb the virus and that this may be mediated by one of the known syncytium-forming viruses which inhabit the respiratory tract (for example, members of the paramyxovirus group). de The and colleagues suggested that intercellular bridges could be seen in NPC tumour material. We have developed a technique which permits the preparation of stable monolayers of viable human lymphoblastoid cell lines. Using this technique we have now demonstrated that EBV can induce fusion between EBV-superinfected lymphoblastoid cells and cells devoid of EBV receptors. PMID- 6253792 TI - Indomethacin and inhibition of protein kinase reactions. AB - Indomethacin, an inhibitor of prostaglandin biosynthesis, is useful in studies aimed at understanding the metabolism and physiological function of prostaglandins. A recent report showing that indomethacin at 10(-7) M potently inhibits the cyclic AMP-dependent protein kinases (cAMP-PrK) from ileal mucosa in the presence or absence of cyclic AMP, suggests how indomethacin may antagonize prostaglandin action on ileal mucosa. It also suggests that indomethacin might be useful in studying the properties and functions of protein kinase reactions. Inhibitors of prostaglandin biosynthesis, such as sodium salicylate and acetylsalicylate, at concentrations near 10(-2) M, have been shown to inhibit bovine diaphragm protein kinase only in the presence of cAMP, while stimulating it in the absence of cAMP. We report here that complete inhibition of cAMP-PrKs by indomethacin requires a concentration of 10(-3) M and is not tissue-specific, and that the effect of indomethacin is concentration dependent above 2 x 10(-4) M for the cAMP-dependent, and above 10(-3) M for cAMP-independent PrKs. These results contrast previous ones. PMID- 6253793 TI - Movable genes. PMID- 6253795 TI - DNA N-glycosylases and UV repair. AB - Repair of some DNA photoproducts can be mediated by glycosylic bond hydrolysis. Thus, Escherichia coli endonuclease III releases 5,6-hydrated thymines as free bases, while T4 UV endonuclease releases one of two glycosylic bonds holding pyrimidine dimers in DNA. In contrast, uninfected E. coli apparently does not excise pyrimidine dimers via a DNA glycosylase. PMID- 6253794 TI - Nucleotide sequence of an avian sarcoma virus oncogene (src) and proposed amino acid sequence for gene product. AB - The transforming gene (src) of avian sarcoma virus (ASV) and adjacent regions of the viral genome have been isolated by molelcular cloning of viral DNA. Their nucleotide sequence encompasses the whole of src and the portion of the gene env that encodes gp 37, one of two glycoproteins found in the viral envelope. Src encodes a single, hydrophobic protein with structural features that conform to previous descriptions descriptions of the gene product (pp60src). It appears that a single viral protein is responsible for both the initiation and maintenance of neoplastic transformation by avian sarcoma virus. Neither src nor its product bear any obvious structural relationship to several other viral oncogenes and their encoded proteins. Src is flanked by a repeated nucleotide sequence that may facilitate frequent deletion of the gene from the viral genome. PMID- 6253796 TI - Regulation by angiotensin II of its receptors in resistance blood vessels. AB - The sensitivity of blood vessels to the vasoconstrictor effects of the hormone angiotensin II appears to be modulated by the activity of the renin-angiotensin system. Elevation of circulating angiotensin II levels by sodium depletion or renal artery stenosis is associated with a diminished pressor response to infused angiotensin II (refs 1-3). Conversely, the vasocontrictor response to the hormone is enhanced when endogenous angiotensin II levels are reduced by sodium loading or nephrectomy. The mechanisms of these varying effects are not known, but physiological and pharmacological experiments suggest involvement of the vascular smooth receptor for angiotensin II (refs 5-8). Modification of the interaction between angiotensin II and its vascular receptor, resulting in altered responsiveness to the hormone, could occur either via 'prior occupancy' of receptors by elevated levels of endogenous angiotensin II resulting in fewer free receptors available to respond to circulating angiotensin II (ref. 5), or, elevated levels of angiotensin II could result in a decrease in receptor affinity for the hormone or a decrease in total receptor number in the vascular smooth muscle cell. We now report the first direct evidence, by radioligand binding assay, that angiotensin II regulates the number of its own receptors in resistance vasculature. PMID- 6253797 TI - Endogenous electric field around muscle fibres depends on the Na+-K+ pump. AB - We describe here experiments which reveal a new physiological specialization in the endplate (synaptic) region of skeletal muscle fibres. Using a vibrating microelectrode which can detect small currents flowing in extracellular fluid, we have found that the membrane in the endplate region behaves as though a steady positive current is generated in this location. Current re-enters the fibre in the extrajunctional region. Further experiments show that this current is dependent on the activity of the sodium pump. The electric field created by this current may be important for long-term interactions between muscle and nerve. PMID- 6253798 TI - Active sodium transport by turtle colon via an electrogenic Na-K exchange pump. AB - Active sodium absorption by a variety of epithelia is abolished by ouabain, but the obligatory coupling between the movement of sodium and potassium expected from a basolateral (Na+ + K+) ATPase has not been convincingly demonstrated. According to the model of Koefoed-Johnsen and Ussing, the asymmetric cation selectivities of the apical and basolateral membranes prevent basolateral Na-K exchange from being expressed as opposing transmural ion flows. An additional consequence of this asymmetry is that the short-circuit current (Isc) cannot be identified with the current through the sodium-potassium pump. We used the polyene antibiotic, amphotericin-B, to reduce the resistance and the cation selectivity of the apical membrane of isolated turtle colon so that the basolateral membrane current could be dissected into two components: one through a barium-sensitive potassium channel and another which represents the current associated with ouabain-sensitive, electrogenic, Na-K exchange. Comparison of cation fluxes and short circuit current indicates that in these conditions active sodium absorption is entirely attributable to an electrogenic Na-K pump with a stoichiometry of approximately 3Na:2K. PMID- 6253799 TI - Light-induced changes in membrane current in cone outer segments of tiger salamander and turtle. AB - The peak change in membrane conductance of vertebrate photoreceptors in response to the isomerization of a single photopigment has been estimated from recordings of membrane potential to be about 8 pS in rods and 6 pS in cones. For rods the estimate has been largely confirmed by Yau et al. by directly recording membrane current responses of rod outer segments to single photoisomerizations. However, no similar measurements have been reported for cone outer segments. Here, we report on direct recordings of membrane currents of single cone outer segments using an extracellular patch electrode. The technique was similar to that described by Yau et al. for toad rods. We have measured dark currents of up to 40 pA, and calculate that the conductance change resulting from a single photoisomerization is less than 1 pS. PMID- 6253800 TI - Specific dephosphorylation of membrane proteins in Rous sarcoma virus-transformed chick embryo fibroblasts. AB - Chick embryo fibroblasts (CEF) infected with avian sarcoma virus become rapidly transformed as a result of expression of the viral src gene in the form of a single polypeptide of molecular weight 60,000 (pp60src) with protein kinase activity and suggested preferential association with the plasma membrane. Studies with normal avian and mammalian cells have revealed the presence of an antigenically related protein which seems to have similar kinase activity, but which is present at less than 1% of the levels of virally induced src protein found in transformed cells. As dynamic phosphorylation is important in numerous regulatory processes, the phenotypic expression of transformation may arise from an imbalance in one or more regulatory mechanisms that are controlled by protein phosphorylation. The cell membrane is affected during transformation, including its phosphotransferase activity. The latter has been shown using isolated membrane fractions whose properties may be changed during preparation. Therefore, we have compared the phosphorylation state of individual membrane proteins found in intact normal and RSV-transformed cells and report here the identification of two heavily phosphorylated, acidic membrane proteins in normal CEF which are specifically dephosphorylated on transformation by wild-type and temperature sensitive Rous sarcoma viruses. PMID- 6253801 TI - Continuous production of monoclonal rheumatoid factor by EBV-transformed lymphocytes. AB - Human B lymphocytes are immortalized by Epstein-Barr virus (EBV, ref. 1). The virus can be used to establish lymphoblastoid cell lines that produce and actively secrete specific antibodies. The original method, which we have used for various antigens is based on selection of the specific surface antigen receptor positive lymphocytes from the peripheral blood lymphocytes of a donor who was previously sensitized to the corresponding antigen. Furthermore, by cloning the polyclonal anti-NNP cell line we have produced human monoclonal antibodies for the first time in vitro. About 5-20 microgram ml-1 stably produced specific antibody is obtained in the supernatant of the cell lines. This approach can be used for the in vitro production of monoclonal human autoimmune antibodies by EBV immortalized lymphocytes from patients with autoimmune diseases. We demonstrate the continuous production in vitro of a monoclonal IgM and anti-IgG antibody (rheumatoid factor, r.f.) by a lymphoblastoid cell line established from a patient with rheumatoid arthritis. PMID- 6253802 TI - Single Na+ channel currents observed in cultured rat muscle cells. AB - The voltage- and time-dependent conductance of membrane Na+ channels is responsible for the propagation of action potentials in nerve and muscle cells. In voltage-step-clamp experiments on neurone preparations containing 10(4)-10(7) Na+ channels the membrane conductance shows smooth variations in time, but analysis of fluctuations and other eivdence suggest that the underlying single channel conductance changes are stochastic, rapid transitions between 'closed' and 'open' states as seen in other channel types. We report here the first observations of currents through individual Na+ channels under physiological conditions using an improved version of the extracellular patch-clamp technique on cultured rat muscle cells. Our observations support earlier inferences about channel gating and show a single-channel conductance of approximately 18 pS. PMID- 6253803 TI - Protein-linked RNA of poliovirus is competent to form an initiation complex of translation in vitro. AB - Poliovirus RNA that had been labelled with 125I in the 5'-terminal protein (VPg) was found competent to form an initiation complex of translation in a cell-free reticulocyte lysate. In conditions of ribosome binding, no cleavage occurred between VPg and RNA. We conclude that removal of VPg from poliovirus RNA is not a prerequisite for this RNA to initiate translation in vitro. PMID- 6253804 TI - HCG stimulation of testicular LHRH-like activity. AB - It is well established that the administration of high doses of luteinizing hormone (LH) or human chorionic gonadotropin (HCG) to animals can impair gonadal function in both the male and female. These effects can be duplicated by the administration of LH releasing hormone (LHRH) or its agonists to intact animals, including man. Somewhat surprisingly, recent results have demonstrated that similar impairment of gonadal function by LHRH and its agonists can be achieved in the absence of the pituitary (for review see ref. 7), and the demonstration of specific, high-affinity binding sites for LHRH and its agonists on ovarian luteal cells and on testicular Leydig cells, could mean that LHRH-like factors are involved in the local regulation of the gonads. A further intriguing finding is the striking similarity between the direct, inhibitory effects of LHRH and LH/HCG on the gonads; for example, both treatments reduce LH receptor numbers and the steroidogenic responsiveness of rat Leydig cells. We now offer a possible explanation for this similarity by demonstrating that HCG treatment stimulates the testicular production of a biologically active LHRH-like factor, suggesting that the inhibitory actions of HCG on the Leydig cell may be mediated by the local production of this factor. PMID- 6253805 TI - Gating charge immobilization and sodium current inactivation in internally perfused crayfish axons. PMID- 6253806 TI - Benzodiazepine recognition sites on GABA receptors. AB - A role of gamma-amino butyric acid (GABA) in benzodiazepine actions is supported by the GABA stimulation of membrane-bound and soluble benzodiazepine receptors and preliminary evidence that GABA protects benzodiazepine receptors from heat inactivation. We show here that the GABA receptors labelled by by 3H-muscimol possess a benzodiazepine recognition site, as benzodiazepines, in proportion to their pharmacological activity, protect 3H-muscimol binding from inactivation by heat and the protein modifying reagent iodoacetamide. We also show that benzodiazepines and GABA act at apparently distinct sites to protect benzodiazepine receptors from heat and iodoacetamide. PMID- 6253807 TI - Unifected avian cells contain structurally unrelated progenitors of viral sarcoma genes. AB - A single gene, src of Rous sarcoma virus (RSV) coding for a protein of pp60src, is responsible for the transformation of fibroblasts. DNA sequences homologous to src (the endogenous sarc) are presented in uninfected cells of chickens and other vertebrates. Endogenous nucleotide sequences have also been found in the putative transforming genes of MC29 (ref. 6) and avian erythroblastosis virus. These viruses, however, induce different spectra of tumours in animals. From analysis of a new avian sarcoma virus, Y73, we present here evidence suggesting that multiforms of viral sarcoma genes originated from cellular genetic sequences, and that these viral genes are structurally unrelated, but have similar pathogenicities. PMID- 6253808 TI - Transforming genes of neoplasms induced by avian lymphoid leukosis viruses. AB - Oncogenic avian retroviruses can be classified into three groups: sarcoma viruses, acute leukaemia viruses and lymphoid leukosis viruses (LLVs). Sarcoma and acute leukaemia viruses transform fibroblasts and/or haematopoietic cells in culture and induce tumours with short latent periods in infected birds. In contrast, LLVs do not transform cells in vitro and require long latent periods before formation of neoplasms in vivo. The most frequent neoplasm induced by LLVs is malignant lymphoma of the bursa of Fabricius, but LLVs also induce other neoplasms, including sarcomas, nephroblastomas and erythroblastosis. The genomes of both sarcoma and acute leukaemai viruses contain specific genes responsible for viral oncogenicity, whereas the genome of LLVs apparently includes only genes required for virus replication. The genetic basis for the low oncogenic potential of LLVs is therefore obscure. The present experiments indicate that LLV-induced tumours contain transforming genes that can be detected by transfection of NH 3T3 mouse cells. These transforming genes are not linked to LLV DNA sequences, suggesting that oncogenesis by LLVs may result from indirect activation of cellular transforming genes. PMID- 6253809 TI - Internal mobility of ferrocytochrome c. AB - In the refinement of the X-ray diffraction structures of molecules, it is conventional to introduce atomic 'temperature factors' of the Debye-Waller form to characterize the widths of the electron density peaks corresponding to the atoms. Although these factors are known to include a variety of contributions other than thermal fluctuations of the atomic positions, recent progress in the refinement of protein structures has led to inferences concerning atomic mobilities from the temperature factor data for several proteins. Atomic position fluctuations can be calculated independently by the molecular dynamics method, in which the classical equations of motion for the atoms of an equilibrated protein are solved on a computer. We now show that the X-ray diffraction and dynamical simulation methods yield similar pictures of the atomic mobility in tuna ferrocytochrome c. PMID- 6253810 TI - Guanine nucleotide-binding and autophosphorylating activities associated with the p21src protein of Harvey murine sarcoma virus. AB - The purified p21src protein of Harvey sarcoma virus shows a guanine nucleotide binding activity and, in addition, at elevated temperature an autophosphorylating activity at a threonine residue using as phosphoryl donor GTP or dGTP but not ATP or dATP. These biochemical activities are unique among those associated with transforming proteins of RNA-containing or DNA-containing tumour viruses. PMID- 6253811 TI - Modulation of lateral geniculate neurone excitability by noradrenaline microiontophoresis or locus coeruleus stimulation. AB - The dorsal lateral geniculate nucleus (LGNd) receives afferents from the brainstem which regulate its capacity to transmit visual information from the retina to the striate cortex. One such pathway consists of noradrenaline (NA) containing fibres originating in the locus coeruleus (LC). These provide a dense, uniform, noradrenergic innervation of the LGNd. Electrical stimulation in the LC region has been reported to enhance the responsiveness of LGNd neurones to afferent excitation. Although this effect was abolished when brain NA stores were pharmacologically depleted, it was not established as a direct action of NA on LGNd neurones because of the widespread distribution of LC fibres to many parts of the brain and the long latency of the response. Recently, we observed that NA, applied locally by microiontophoresis with low ejection currents, produced a delayed increase in the firing rate of most spontaneously active LGNd neurones, an effect selectively blocked by alpha-adrenoceptor antagonists. We show here that microiontophoretic NA can mimic the ability of LC stimulation to enhance the synaptic excitation of LGNd neurones. As neither NA nor LC stimulation activated LGNd neurones in the absence of synaptic or glutamate-induced excitation, both appear to act through a neuromodulatory mechanism. The postsynaptic alpha adrenoceptor antagonist WB-4101 blocks the facilitation produced by locally applied NA and by coeruleo-geniculate pathway stimulation, providing evidence for pharmacological identity of the two effects. PMID- 6253813 TI - Endogenous digitalis-like substance in plasma of volume-expanded dogs. PMID- 6253812 TI - Lignans in man and in animal species. AB - In our laboratories, for several years, two phenolic compounds have been detected during gas chromatographic-mass spectrometric analysis of urinary steroid extracts from human and animal species. Although features of the mass spectra of their trimethylsilyl (TMS) ether derivatives resembled those of oestrogens, they were atypical of steroids. The possibility that they were artefacts of the isolation procedures was discounted after careful studies with blanks, by varying the extraction method and because they were present almost exclusively as conjugates of glucuronic acid. Several of the general characteristics of the unknown compounds were reported after one (referred to as compound 180/442) was found to have a cyclic pattern of excretion during the menstrual cycle of an adult vervet monkey (Fig. 1). An investigation of the nature and distribution of the compounds has shown them to be urinary constituents in humans, baboons, vervet monkeys and rats, and further related compounds have been detected, so far only in vervet monkey urine. We now report spectroscopic and chemical studies that show the two original compounds to be lignans, which have a 2,3 dibenzylbutane skeleton as their basic structure. Unlike all previously known natural lignans, invariably of plant origin, the two mammalian compounds carry phenolic hydroxy groups only in the meta position of the aromatic rings. PMID- 6253814 TI - Dimeric tRNA precursors in yeast. AB - Two DNA fragments, each containing tRNA(Arg)3 and a tRNA(Asp) gene in close conjunction, have been isolated from different genomic regions of Saccharomyces cerevisiae. Nucleotide Nucleotide sequence analysis of the gene regions revealed that in both fragments the tRNA(Arg)3 coding region is located 5'-proximal to the tRNA(Asp) coding region. They are separated by an identical spacer of 10 nucleotides. Although the 5'-flanking sequences are different in the two plasmids, some similarities are observed. To test the mode of expression of this gene configuration, we transcribed the DNA fragments in a Xenopus oocyte nuclear extract. Specific transcription of the yeast tRNA genes took place in an RNA precursor which comprised both tRNA species. We report here that the precursor RNA was processed to the mature-sized tRNA molecules, indicating the presence of an enzyme activity in the Xenopus nucleus capable of cutting a dimeric tRNA precursor. This is the first observation of a eukaryotic dimeric tRNA precursor. PMID- 6253815 TI - The protein-coding sequence of the bovine ACTH-beta-LPH precursor gene is split near the signal peptide region. AB - The pituitary hormones corticotropin (ACTH) and beta-lipotropin (beta-LPH) are formed from a large common precursor. Recently, we have elucidated the whole primary structure of the bovine ACTH-beta-LPH precursor (designated alternatively as preproopiocortin) by determining the nucleotide sequence of cloned DNA complementary to the mRNA coding for the precursor protein. The amino acid sequence assigned has disclosed a characteristic repetitive structure of the ACTH beta-LPH precursor. The repetitive units of the precursor protein each contain a melanotropin (MSH) sequence (alpha-, beta- or gamma-MSH) as well as other peptide components such as beta-endorphin and corticotropin-like intermediate lobe peptide (CLIP). The repetitive units as well as their peptide components are each bounded by paired basic amino acid residues, which apparently represent the sites of proteolytic processing. Several studies have confirmed the translational initiation site and protein structure assigned (see also ref. 11 and refs therein). In view of the recent knowledge about the organization of eukaryotic genes (see refs 12, 13 for reviews), it would be of particular interest to investigate the relationship between the repetitive structure of the ACTH-beta LPH precursor containing different functional components and the arrangement of the protein-coding sequence in its gene. We have now isolated and characterized bovine genomic DNA fragments encoding this precursor protein and have demonstrated that the protein sequence is encoded by two non-consecutive DNA segments. An intron (intervening sequence) of approximately 2.2 kilobase pairs separates the smaller exon (mRNA-coding sequence), which contains the gene sequence encoding the signal peptide, from the larger exon, which contains the gene sequence for most of the protein structure, including the known biologically active component peptides. PMID- 6253816 TI - Methyltetrahydrofolate is a potent and selective agonist for kainic acid receptors. PMID- 6253817 TI - Expression of a transposable antibiotic resistance element in Saccharomyces. AB - Some eukaryotic genes can be expressed in bacteria but there are few examples of the expression of prokaryotic genes in eukaryotes. Antibiotic G418 is a 2 deoxystreptamine antibiotic that is structurally related to gentamicin but has inhibitory activity against a much wider variety of pro- and eukaryotic organisms. In bacteria, resistance to G418 can be determined by several plasmid encoded modifiying enzymes and, in view of the broad spectrum of activity of G418, we considered that this antibiotic might be useful as a selective agent for the introduction of these antibiotic resistance genes into a eukaryotic organism such as Saccharomyces cerevisiae. Additional impetus for these experiments came from the knowledge that certain of the G418-resistance determinants in bacteria are carried on transposable elements; a study of the properties of these elements in eukaryotes would be intriguing. PMID- 6253818 TI - Leaky +1 and -1 frameshift mutations at the same site in a yeast mitochondrial gene. AB - Two mutations in a mitochondrial structural gene, which cause leaky premature polypeptide chain termination and leaky growth, are +1 and -1 frameshifts in the same run of five T residues. The partial restoration of reading frame is probably due to ribosomal frameshifting at this site, and may be promoted by the unique structure of the yeast mitochondrial t RNAPhe. PMID- 6253819 TI - Different postsynaptic events in two types of retinal bipolar cell. AB - The first synapse in the vertebrate visual system is made between the photoreceptors and the biopolar cells. Bioplar cells fall into two distinct classes according to whether the cell hyperpolarizes or depolarizes to small centred spots of light. Most evidence indicates that the light-induced hyperpolarization of the photoreceptprs suppresses transmitter release from the synaptic terminals, and it is probable that the differences between the two bipolar cell classes results from the different actions of the photoreceptor transmitter. In analysing the membrane potential fluctuations in both types of bipolar cell we find that the voltage noise spectra differ. It is to be expected that postsynaptic noise would be composed of the sum of noise generated in and transmitted from the cones and the noise arising from the statistical nature of synaptic transmission. We report here evidence for two such components in the voltage noise spectra recorded from each type of bipolar cell. The differences in the frequency distribution of the presumed transmitter-related components indicates that the transmitter generates events of longer duration in the depolarizing biopolar cells. PMID- 6253820 TI - Met-enkephalin-Arg6-Phe7, present in high amounts in brain of rat, cattle and man, is an opioid agonist. AB - The enkephalins Met-enkephalin and Leu-enkephalin were first isolated from porcine brain by Hughes and co-workers. We have recently isolated from bovine adrenals another enkephalin with the structure Tyr-Gly-Gly-Phe-Met-Arg-Phe, or Met-enkephalin-Arg6-Phe7 (ref. 2). We report here that this new heptapeptide is found in human, rat and bovine striatum in concentrations comparable with or greater than that of Leu-enkephalin. This molecule should not be considered as a mere precursor of Met-enkephalin. A pharmacological study indicates that this naturally occurring enkephalin has similar properties to the two enkephalins characterized earlier. PMID- 6253821 TI - Development of virus non-producer lymphosarcomas in pet cats exposed to FeLv. AB - Naturally occurring oncoviruses of several species are transmitted contagiously and cause lymphosarcoma (LSA) or leukaemia in their hosts. All naturally occurring oncoviruses replicate in vivo in the tumours they induce or, as with bovine leukaemia virus, can be isolated from tumour cells grown in short-term cell culture. However, we have shown that feline leukemia virus (FeLV) is not present in a significant minority of pet cats that develop LSA. Unlike experimentally induced virus-negative leukaemias and sarcomas of other species, LSA cells from FeLV-negative LSA cats lack any FeLV proteins, including p15 or p12, and complete functional copies of FeLV provirus and thus do not produce FeLV when grown in cell culture. Thus, except for FeLV, the naturally occurring animal leukaemogenic oncoviruses seem to induce only virus-producing lymphoid tumours. Our earlier findings prompted a study to determine the frequency of occurrence of FeLV non-producer (NP) LSA in pet cats and whether NP LSAs develop in cats exposed to FeLV. We report here epidemiological data which indicate that development of NP LSAs in pet cats is associated with exposure to FeLV and suggest that FeLV may be the aetiological agent for FeLV NP feline LSAs. Thus, feline NP LSAs may be suitable for studying the potential viral aetiology and mechanism of leukaemogenesis of human lymphoid tumours in which no oncoviruses have, as yet, been proved to cause the disease. PMID- 6253822 TI - Biosynthesis and processing of cellular and viral polyproteins. PMID- 6253823 TI - Mutants of avian myelocytomatosis virus with smaller gag gene-related proteins have an altered transforming ability. AB - Avian myelocytomatosis virus strain MC29 is a replication-defective avian oncovirus which in newborn chickens causes myelocytomatosis and liver and kidney tumours. In vitro infection of bone marrow cells gives rise to colonies of transformed macrophage-like cells, and cloned viruses is also capable of transforming fibroblasts. The genome of MC29 contains cellular sequences which are closely related to those in other defective leukaemia viruses with similar transforming spectra. Consequently, these cellular sequences have been postulated to represent a new oncogene which has been designated mac, for macrophage transformation. MC29-transformed cells contain a gag gene-related protein of a 110,000 molecular weight (MW) (p110), which by tryptic peptide analysis has been shown to be a fusion product comprised of a gag gene-derived sequences and sequences which are presumed to be coded by the adjacent mac gene. These findings suggest that this protein may be implicated in transformation by MC29. We now describe three mutants of MC29 and synthesize smaller gag gene-related proteins. These mutants have an altered ability to transform bone marrow cells but not fibroblasts. This demonstrates for the first time a direct involvement of the p110 protein of MC29 in transformation. PMID- 6253824 TI - Vitamin E modulates the lipoxygenation of arachidonic acid in leukocytes. AB - The arachidonic acid released from cellular phospholipids of specifically stimulated platelets and leukocytes is oxygenated enzymatically by two major pathways. A complex cycloxygenase converts some of the free arachidonic acid to labile endoperoxides that are transformed to prostaglandins, thromboxanes and prostacyclin (PGI2). Lipoxygenases convert part of the arachidonic acid to unstable hydroperoxy-eicosatetraenoic acids (OOHETEs) that are transformed to monohydroxyeicosatetraenoic acids (HETEs), oligohydroxy-eicosatetraenoic or eicostatrienoic acids such as di-HETEs and tri-HETEs, and, in some instances, more complex humoral mediators, including slow-reacting substances. Both the nature of the HETEs and the ratio of the HETEs to the cyclo-oxygenase products are specific characteristics of each type of cell. In human neutrophils, the sum of the lipoxygenase products 5-HETE, 11-HETE and 5,12-di-HETE substantially exceeds the total amount of PGE2 and other cyclo-oxygenase metabolites that are generated concurrently, and the endogenous lipoxygenase products regulate neutrophil function. The present data indicate that vitamin E (alpha-tocopherol) bidirectionally modulates the activity of the lipoxygenase pathway of human neutrophils in vitro. Normal plasma concentrations of alpha-tocopherol enhance the lipoxygenation of arachidonic acid, whereas higher concentrations of alpha tocopherol exert a suppressive effect that is consistent with its role as a hydroperoxide scavenger. PMID- 6253825 TI - Herpes simplex virus in latent infection. PMID- 6253826 TI - A new class of angiotensin-converting enzyme inhibitors. AB - Much current attention focuses on the renin-angiotensin system in relation to mechanisms controlling blood pressure and renal function. Recent demonstrations (ref. 1, ref. 2 and refs therein) that angiotensin-converting enzyme inhibitors show promising clinical antihypertensive properties have been of particular interest. We now report on the design of a novel series of substituted N carboxymethyl-dipeptides which are active in inhibiting angiotensin-converting enzyme at nanomolar levels. We suggest that these compounds are transition-state inhibitors and that extensions of this design to other metalloendopeptidases merit further study. PMID- 6253827 TI - Herpes simplex virus DNA sequences in the CNS of latently infected mice. AB - It has been amply documented that herpes simplex virus (HSV) persists in sensory ganglia of the peripheral nervous system (PNS). In contrast, HSV latency in the central nervous system (CNS) has not been well characterized. Corneal inoculation of virus results in a productive viral infection in the CNS during the first week after inoculation, indicating that the virus can progress from the PNS to the CNS. During latency, HSV has been found by co-cultivation of CNS tissue in only a very small fraction of inoculated mice. We have used here molecular hybridization techniques to analyse the fate of viruses that reach the CNS by anatomical pathways. We show that 6 days after corneal inoculation of HSV-1 a productive viral infection was present in brain tissue as well as in peripheral ganglia in at least 90%F of the inoculated mice. The mortality during this acute phase was only 2%. In the survivors, latent HSV could be recovered by explantation from 95% of the trigeminal ganglia, but only 5% of the brain tissue explants of the same mice yielded infectious virus. However, HSV DNA sequences were detected in the brains of 30% of mice which harboured latent HSV in their trigeminal ganglia. These results suggest that viruses that progress from the PNS into the CNS are not eliminated, but are capable of establishing a latent infection in the CNS that cannot be reactivated by explantation techniques. PMID- 6253828 TI - Noradrenergic transmission. PMID- 6253829 TI - Opiate receptors and adrenal medullary function. PMID- 6253830 TI - Voltage-dependent translocation of the asialoglycoprotein receptor across lipid membranes. AB - A membrane receptor protein for asialoglycoproteins induces voltage-dependent increases in ion conductance across a lipid bilayer, probably reflecting penetration of the protein into the bilayer towards an electrically positive pole. In the presence of specific ligand for the receptor, this penetration leads to a 'translocation' of the receptor from one side of the bilayer to the other. These observations suggest a mechanism by which biological membranes might regulate the disposition of their proteins, and a way in which membrane receptors involved in endocytosis might be spared lysosomal destruction in order to be recycled to the plasma membrane. PMID- 6253831 TI - The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. AB - Despite its very potent vasodilating action in vivo, acetylcholine (ACh) does not always produce relaxation of isolated preparations of blood vessels in vitro. For example, in the helical strip of the rabbit descending thoracic aorta, the only reported response to ACh has been graded contractions, occurring at concentrations above 0.1 muM and mediated by muscarinic receptors. Recently, we observed that in a ring preparation from the rabbit thoracic aorta, ACh produced marked relaxation at concentrations lower than those required to produce contraction (confirming an earlier report by Jelliffe). In investigating this apparent discrepancy, we discovered that the loss of relaxation of ACh in the case of the strip was the result of unintentional rubbing of its intimal surface against foreign surfaces during its preparation. If care was taken to avoid rubbing of the intimal surface during preparation, the tissue, whether ring, transverse strip or helical strip, always exhibited relaxation to ACh, and the possibility was considered that rubbing of the intimal surface had removed endothelial cells. We demonstrate here that relaxation of isolated preparations of rabbit thoracic aorta and other blood vessels by ACh requires the presence of endothelial cells, and that ACh, acting on muscarinic receptors of these cells, stimulates release of a substance(s) that causes relaxation of the vascular smooth muscle. We propose that this may be one of the principal mechanisms for ACh-induced vasodilation in vivo. Preliminary reports on some aspects of the work have been reported elsewhere. PMID- 6253832 TI - Do human platelets have opiate receptors? AB - In their study of prostaglandin E1 (PGE1)-sensitive adenylate cyclase (AC) in rat brain homogenates, Collier and Roy claimed that the activity of this enzyme is inhibited by opiates. They also proposed that opiates exert their analgesic and allied effects by inhibiting AC of neurones that are normally stimulated by E prostaglandins. Studies using neuroblastoma x glioma hybrid cells supported this hypothesis. However, subsequent studies with mammalian brain and rat brain tissue slices yielded conflicting results. PGE1 also inhibits platelet aggregation, probably through activation of platelet AC. Gryglewski et al. showed that morphine inhibits the anti-aggregating effect of PGE1 on ADP- and adrenaline induced platelet aggregation, and suggested that the inhibition by morphine is mediated through platelet AC activity. We report here our attempts to reproduce the results of Gryglewski et al. and our examination of the effect of morphine on PGE1-sensitive AC activity in platelet lysates and on PGE1-induced accumulation of cyclic AMP in intact platelets. The possible existence of opiate receptors in platelets was also assessed by direct binding studies with 3H-etorphine. In contrast to Gryglewski et al., we could not detect any effect of opiates on the aggregation of human platelets, nor did we find any other evidence supporting the presence of opiate receptors in these cells. Thus we conclude that the presence of opiate receptors in human platelets is unlikely. PMID- 6253833 TI - Induction of diabetes by cumulative environmental insults from viruses and chemicals. AB - Encephalomyocarditis virus (EMC) induces diabetes in certain inbred strains of mice by infecting and destroying pancreatic beta cells, the severity of the diabetes depending on the number of beta cells destroyed. In strains of mice resistant to EMC-induced diabetes, insufficient beta cells are damaged to alter glucose homeostasis. However, diabetes can be produced in many species by streptozotocin, a highly specific beta-cell toxin. Here, we used concentrations of streptozotocin that did not produce diabetes, but reduced the beta-cell reserve. When strains of mice normally resistant to EMC-induced diabetes were first treated with sub-diabetogenic doses of streptozotocin, then infected with EMC virus, diabetes developed. Furthermore, when mice were infected with viruses such as Coxsackie B3 and B5, which ordinarily produce little if any beta-cell damage, diabetes developed if the mice were first treated with sub-diabetogenic doses of streptozotocin. These findings suggest that diabetes may result from cumulative beta-cell damage induced by sequential environmental insults. PMID- 6253834 TI - Retroviral antigens on gs- chf- leukocytes. AB - It has recently been suggested that the endogenous retroviruses present in many different species might be involved during stimulation of the immune system of their hosts. We have now studied the expression of two avian retroviral antigens p27 and gp85 in chicken lymphoid cells by indirect immunofluorescence (IIF) and by complement-dependent microcytotoxicity (CDM). We have now found that these viral antigens are expressed in peripheral blood leukocytes of adults and embryos and in splenic and bursal lymphocytes of Spafas gs- chf- chickens but they are not expressed in fibroblasts cultured from the feather follicles of the same individual adult birds nor in fibroblasts cultured from embryos of the same flock. The differential expression of viral antigens in leukocytes may be related to a specific property or function of these cells. PMID- 6253835 TI - Conservation and rearrangement of mitochondrial structural gene sequences. AB - Mitochondria contain the simplest DNA molecules that are present in eukaryotes. Mitochondrial DNA (mtDNA) is easily purified, and is an important model system for studying eukaryote gene structure and basic molecular processes. The protein sequences of mitochondrial gene products have been shown to be conserved from yeast to man, and there are definite similarities at the DNA sequence level. In contrast, the overall organization of the mitochondrial genome is drastically different in these organisms. To understand this, we need to extend work on mtDNA to a wider range of species. We have chosen to study the mtDNA of Aspergillus nidulans because a particularly comprehensive analysis of this system can be achieved using genetics as well as biochemistry, and like most eukaryotes it is an obligate aerobe, whereas Saccharomyces cerevisiae is not. We have investigated whether defined pieces of particular yeast mitochondrial genes show enough homology to Aspergillus mtDNA fragments to enable the corresponding Aspergillus genes to be located on the physical map. The results reported here show that this is the case for all five genes tested, and present the first data on the physical organization of the structural genes in the mitochondrial genome of A. nidulans. PMID- 6253836 TI - Salt-dependent dynamic structure of poly(dG-dC) x poly(dG-dC). PMID- 6253837 TI - Effects of lithium chloride on lateral line responses in Carassius auratus. PMID- 6253838 TI - Heterophylic action of ecdysterone. Effect on the cAMP-protein kinase system in mouse. PMID- 6253839 TI - Swine vesicular disease viruses isolated from healthy pigs in non-epizootic period. I. Isolation and identification. AB - A total of 524 fecal samples were collected from healthy swine of 36 hog farms scattered all over Japan from which had been detected neutralizing antibody against swine vesicular disease (SVD) virus. A virus was isolated from 21 of them. It was neutralized by antiserum against SVD virus. Of the 21 samples, 19 were derived from six farms, in areas which remained to be free from SVD in the past years and two from a farm where SVD broke out 18 months before. The cross neutralization test was carried out with seven strains of SVD virus isolated from healthy pigs (SVDV-H) and five strains of SVD virus isolated from diseased pigs (SVDV-D). There was, however, no significant difference in antigenicity between the two groups. Some strains of SVDV-H were antigenically close to the Faulkner strain of Coxsackie B5 virus, and others to the freshly isolated strain of this virus. Neutralizing antibody of low titer against SVD virus was detected from pigs kept in areas free from SVD. It was presumed to have been produced in these pigs involved in silent infection with this virus. PMID- 6253840 TI - Characterization of adenosine receptors in rat brain by (-)[3H]N6 phenylisopropyladenosine. PMID- 6253841 TI - Beta adrenergic receptors in the parathyroid glands. AB - The location of beta-adrenoceptors in human parathyroid gland was studied using an immunohistochemical method. Frozen sections of human parathyroid glands, taken from surgical samples, were treated with (-)-alprenolol, washed and exposed to ( )-alprenolol antibodies conjugated with fluorescent dyes. The (-)-alprenolol was bound to the parathyroid principal cells and to the main blood vessels. On the contrary, adrenergic nerve fibres, demonstrated with formaldehyde fluorescence technique, were only located within the walls of main blood vessels. The findings are discussed. PMID- 6253843 TI - Effect of diphenolic laxatives on Na+-K+-activated ATPase and cyclic nucleotide content of rat colon mucosa in vivo. AB - 1. The effect of bisacodyl and oxyphenisation on the Na+-K+- and Mg2+-activated ATPase and on the mucosa levels of cAMP and cGMP was investigated in transporting ligated loops of the rat colon in acute studies and in chronic feeding experiments 2. The specific activity of the Na+-K+-ATPase was lowered in both types of experiments, concomitantly with a reduction in net sodium absorption. The specific activity of the Mg2+-activated ATPase was unaffected. 3. The cAMP content per mg protein was elevated and the cGMP content decreased in the acute experiments in which the effect on transport was most marked. The content of cyclic nucleotides returned to normal within 2 h whereas absorption, Na+-K+ ATPase specific activity and the mucosal potential difference were still significantly depressed at that time. In chronic experiments with bisacodyl, cAMP was not affected and cGMP was increased in colon loops exhibiting reduced absorption. 4. The results indicate that the inhibition of the Na+-K+-activated ATPase by diphenolic laxatives may play a role in the inhibition of intestinal fluid absorption caused by these compounds. The increase of cAMP in acute experiments could point to a cAMP-mediated stimulation of secretory processes under this condition. PMID- 6253844 TI - [Various results of multidisciplinary treatment of children with cancer]. PMID- 6253845 TI - [Cancer and virus]. PMID- 6253846 TI - Antimicrobial agents and the central nervous system. AB - There is an ever-expanding number of antimicrobial agents available for the clinician to use to combat infections. We review the majority of such agents that are currently available relative to their theoretical or proven efficacy in the treatment of CNS infections. Due to the unique ability of the CNS to exclude many agents delivered via the blood stream, easily administered and efficacious therapy remains a problem. Based on the pharmacokinetics of anti-infective drugs and their antimicrobial spectrum, at present a penicillin derivative or chloramphenicol should be used whenever possible because parenteral therapy will usually achieve the desired results. In many neurosurgery-associated infections, intrathecal or intraventricular antibiotics may be required to supplement parenteral treatment and/or surgical intervention. Some of the more promising agents (such as rifampin, trimethoprim-sulfamethoxazole, and metronidazole) await further clinical trials to establish their place in the therapeutic armamentarium. Careful, randomized, prospective studies of prophylactic antibiotics must be performed in the neurosurgical setting. A group of tables are included that summarize the expected spinal fluid levels, the sensitivities of organisms commonly causing neurosurgical infections, doses of drugs given intrathecally or intraventricularly, and recommended regimens for certain infections. PMID- 6253842 TI - Influence of vasoactive intestinal polypeptide on net water flux and cyclic adenosine 3',5'-monophosphate formation in the rat jejunum. AB - 1. The effects were studied of vasoactive intestinal polypeptide (VIP), theophylline, and morphine on net water flux and cyclic adenosine 3',5' monophosphate (cyclic AMP) levels in the jejunum of anaesthetized rats in vivo and of VIP and morphine on adenylate cyclase activity in rat epithelial cell membranes in vitro. 2. Infusion of VIP (0.1-2 x 10(-9) mol/min/kg) dose dependently caused a reversal from net water absorption to net secretion; 2 x 10( 9) mol/min/kg enhanced the mucosal cyclic AMP content by 67%. 3. Theophylline (5 mg/ml, intraluminally) enhanced the effect of intra-arterial infusion of VIP (2 x 10(-9) mol/min/kg) as to net water secretion and increase in mucosal cyclic AMP content. 4. Pretreatment with morphine (5 mg/kg, s.c.) did not influence the effects of VIP on net water flux and on mucosal cyclic AMP content. 5. Atropine (2 mg/kg, s.c.) also failed to reduced the effect of VIP (0.4 x 10(-9) mol/min/kg) on net water flux. 6. Stimulation of adenylate cyclase activity was a function of VIP concentration over a range of 1 x 10(-10)-1 x 10(-7) M. Morphine (up to 1 x 10(-3) M) failed to influence stimulation of adenylate cyclase by VIP. 7. The finding that low doses of VIP, which already have an effect on net water flux, fail to increase cyclic AMP levels makes it likely that other mediators besides cyclic AMP are involved in the effect of VIP on net water flux. Some of the present results, however, support the assumption that VIP stimulates intestinal fluid secretion by increasing mucosal cyclic AMP levels. PMID- 6253847 TI - Discrete states of responsiveness of a locust muscle gamma-aminobutyric acid receptor: the influence of extracellular ion concentrations. PMID- 6253848 TI - Biochemical evidence for glutamate as a transmitter in hippocampal efferents to the basal forebrain and hypothalamus in the rat brain. PMID- 6253849 TI - Patterns of functional synaptic connections in organized cultures of cerebellum. PMID- 6253850 TI - [Case of Central European tick-borne encephalomyelitis with a rare clinical course]. PMID- 6253851 TI - [Viral neuraxitis. Further studies of the current epidemiological and clinical aspects]. AB - An epidemiological and clinical investigation upon ten cases of acute viral neuraxitis observed in the country of Alessandria between January 1978 - January 1979, is reported. Four cases of neuraxitis were due to coxsackie B4 virus, two to coxsackie B3, two to influenza type A and one to influenza type B virus, one to rubella and one to varicella-zooster virus. In all the cases blood chemistry, clinical and instrumental examinations (EEgraphy, cerebral scintigraphy and angiography) were coupled with determination of serum levels of complement fixing, haemagglutination inhibiting and neutralizing antibodies on two successive specimens, isolation of virus from cerebrospinal fluid, faeces and pharingeal secretions. Some particularly interesting epidemiological, immunological and clinical features of these neuraxitis are more fully discussed. PMID- 6253852 TI - [Lesions of the genital system associated with brenner tumor]. PMID- 6253853 TI - [Thecoma and pregnancy]. PMID- 6253854 TI - Subcellular particles in synovial fluids and synovial cells. AB - Membranous particles of mycoplasma-like appearance (100 to 300 nm in diameter) and non-membranous particles which are viral-like (20 to 80 nm in diameter) were observed in negatively-stained preparations of synovial fluid pellets from patients with rheumatoid arthritis (RA), osteoarthrosis (OA) or psoriatic arthritis (PA). The incidence of positive fluids were: membranous particles- 22/28 (RA), 7/11 (OA), 1/3 (PA); non-membranous particles--12/28 (RA), 1/11 (OA), 1/3 (PA). Eight of the RA fluids, one OA and one PA fluid were positive for both types of particle. The observation of an increased frequency of viral-like particles in RA synovial fluids compared to OA and PA fluids is of possible aetiological interest. Viral-like particles were also observed in the nuclei of rheumatoid synovial macrophage syncytia by electron microscopy of ultra-thin sections of cultured cells. PMID- 6253855 TI - A longitudinal serological survey of respiratory virus infections in lambs. PMID- 6253856 TI - Placental concentrations of progesterone, estradiol-17 beta, and cyclic AMP at delivery. AB - In contrast to most mammals, human parturition is not preceded by a rise in the estradiol : progesterone ratio in peripheral plasma. Thus tissue concentrations of progesterone, estradiol-17 beta, and cyclic adenosine monophosphate (AMP) were measured in placentas obtained after spontaneous vaginal delivery (SVD, N = 11), after oxytocin-induced labor (OXIL, N = 5), and at elective cesarean section (ECS, N = 8). Both progesterone and estradiol were higher in placentas obtained from SVD compared with those from ECS (progesterone: 2.95 +/- 0.26 versus 1.96 +/ 0.29 ng/mg tissue, P < .025; estradiol: 33.6 +/- 5.2 versus 26.4 +/- 3.8 pg/mg). Placentas from OXIL had intermediate progesterone (2.50 +/- 0.47 ng/mg) but the highest estradiol concentration (41.4 +/- 3.2 pg/mg). Cyclic AMP was 29.8 +/- 1.5, 39.6 +/- 8.0, and 35.9 +/- 3.9 pmoles/100 mg tissue in SVD, OXIL, and ECS placentas, respectively. Thus no rise in the placental estradiol : progesterone ratio was found in association with spontaneous labor. PMID- 6253857 TI - Hypothalamo-pituitary-adrenal axis in patients with prostatic carcinoma. AB - Insulin-induced pituitary growth hormone (GH), adrenocorticotrophic hormone (ACTH) and adrenal cortical response were studied in 12 patients with prostatic carcinoma. 3 patients demonstrated significant abnormal GH release associated with concentrations which remained on a high plateau during the study. 5 patients showed lack of ACTH-cortisol response to insulin-induced hypoglycemia. Those patients subsequently presented clinically with rapidly progressing disease. PMID- 6253859 TI - Suppression of the leukocyte adherence inhibition response to murine-sarcoma virus-induced tumors by tumor-associated suppressor cells. AB - The tumor-specific leukocyte adherence inhibition (LAI) response of lymphoid cells from C57B1/6 mice sensitized to a murine-sarcoma-virus (MuSV)-induced tumor was inhibited by adherent phagocytic spleen cells from mice with progressively growing RBL-5 tumors. Both the direct LAI response and the formation of the mediator of LAI were sensitive to the suppressive activity of the progressor spleen macrophages. Suppression of LAI was not restricted by H-2 differences between the sensitized lymphocytes and progressor macrophages. Suppression was also nonspecific since the antibody plaque-forming cell response of normal lymphocytes to triphenylated hemocyanin was lowered by the addition of progressor spleen macrophages. Removal of adherent suppressor macrophages during the late stages of tumor growth revealed greatly elevated LAI reactivity not detectable in an unfractionated population. PMID- 6253858 TI - Detection of liver metastases with 5'-nucleotide phosphodiesterase isozyme-V in gastrointestinal cancer patients. AB - An evaluation of the 5'-nucleotide phosphodiesterase isozyme V (5'-NPD-V) test for liver metastases in gastrointestinal (GI) cancer patients was undertaken with a coded serum panel provided by NCI Mayo Clinic. Upon decoding, 28 of 30 patients (93%) with known liver metastases and 11 or 32 patients (36%) with no known liver metastases were positive. In 20 patients with various benign GI diseases, there were 6 (30%) positive for 5'-NPD-V. 2 of these positive patients with benign GI diseases had identifiable liver disorders. Statistical analysis of the data supports 5'-NPD-V can discriminate between GI cancer patients with and without liver metastases and patients with benign GI diseases. PMID- 6253860 TI - From hospital to nursing home: evaluation plan helps bridge the gap between acute and long term care concerns. PMID- 6253861 TI - [On the problem of selective embolization of the maxillary artery (author's transl)]. PMID- 6253863 TI - Fatal herpes simplex encephalitis with demonstration of virus in the olfactory pathway. AB - A fatal case of herpes simplex encephalitis contained viruses within the olfactory pathway but not in the trigeminal ganglia. This finding supports the theory that the olfactory nerves are the portal of entry in adult herpes simplex encephalitis. PMID- 6253862 TI - Control of BK virus antibodies in contacts of patients under chronic hemodialysis or after renal transplantation (by an enzyme linked immunosorbent assay). AB - Elisa technique for IgG humoral BK virus antibodies titration is not time consuming, not expensive and brings results in accordance with those obtained by HI. It was observed among adults attending patients in chronic hemodialysis and renal transplantation centers an antibody level similar to observed titers in control subjects. PMID- 6253864 TI - Mucinous colorectal carcinoma: immunopathology and prognosis. AB - A total of 519 colorectal carcinomas were examined for the presence or absence of mucinous differentiation by means of microscopical morphometry. Of these, 28% had objectively measurable amounts of mucinous tumour epithelium. Tumours with > 50% mucinous areas (14%) had significantly poorer prognosis than non-mucinous in stages A and C, while mucinous differentiation did not correlate with prognosis in stages B and D. Lymph nodes regional to mucinous tumours had significantly less paracortical response, and those with < 50% mucinous differentiation, significantly less perivascular lymphocyte cuffing at the tumour margins. These lymph node and stromal compartments are putative T-lymphocyte areas, and hence our findings suggest that mucinous tumours are either less stimulatory or perhaps inhibitory of cell-mediated immunity. PMID- 6253865 TI - Melanotic neuroectodermal tumour of infancy arising in anterior fontanelle. AB - A case is described of a melanotic neuroectodermal tumour which developed in the anterior fontanelle of the skull of a Melanesian girl during the first 7 mth of life. PMID- 6253866 TI - The natural history of herpes simplex virus infection of mother and newborn. AB - The controlled evaluation of vidarabine as therapy of neonatal herpes implex virus (HSV) infection provided an opportunity to collect data to further assess the natural history of maternal and newborn infections. Women delivering infected babies were young, nulliprous, and infrequent aborters. Nearly 50% of the gestations ended in premature labor. Maternal infection was asymptomatic in 39 of 56 (70%) of the mothers, at the time of delivery. However, risk factors included a past history of genital herpes at any time and exposure to a sexual partner with presumed HSV lesions. Associated diseases in children born to these women were common. Premature infants had an incidence of respiratory distress of 52% (14 of 27). Eight of 29 (28%) term newborns had a bacterial infection, antedating the onset of neonatal HSV infection. Virologic studies on infected newborns confirmed that skin lesions were the most frequent site for virus retrieval. Progression of disease from isolated skin lesions was common, occurring in 70% of babies whose presenting sign was skin vesicles. CSF was virus-positive from 14 babies and more frequently in those with localized CNS disease. Importantly, brain biopsy was necessary for diagnosis in four cases. Finally, neither the presence or absence of antibodies to HSV was useful in predicting either presentation or outcome of infection. These studies further emphasize the complex nature of HSV infections of the newborn and need for tertiary care. PMID- 6253867 TI - Wilms tumor in five cousins. AB - Wilms tumor developed in five cousins in a family. Two with bilateral tumors have died, but three with unilateral lesions have survived. None of the patients had associated chromosome defects, aniridia, hemihypertrophy, or other anomalies. The pattern of Wilms tumor in the family is consistent with several postulated mechanisms of inheritance of the neoplasm, and shows that relatives within affected families may be at risk. PMID- 6253868 TI - Unusual eye abnormalities associated with congenital cytomegalovirus infection. AB - Seven children with congenital cytomegalovirus infection demonstrated a higher than expected incidence of "rare" ophthalmological abnormalities, including anophthalmia and Peters' anomaly. These data suggest that appropriate investigation for evidence of cytomegalovirus infection should be instituted in any child with congenital ocular defects. PMID- 6253869 TI - Prevention and treatment of neonatal herpes. PMID- 6253870 TI - The effect of papaine on the time course of the end-plate current. AB - Papaine is known to detach cholinesterases from the synaptic cleft. It could be expected that this would result in an increase of the amplitude and half-time of the end-plate current. Thus, the effect of papaine on the end-plate current. Thus, the effect of papaine on the end-plate current should be similar to the effect of anticholinesterase methanesulfonylfluoride. The end-plate current was recorded in frog skeletal muscle at various levels of membrane potential, before and after papaine was added to the bath. The effect of papaine was an increase of the half-time of the end-plate current, similarly as after treatment of the muscle by methanesulfonylfluoride. It seems that both papaine and methanesulfonylfluoride have a similar mechanism of action. In either experimental condition hydrolysis of transmitter is decreased or abolished, which results in an increase of the half-time of the end-plate current. PMID- 6253871 TI - Lactate dehydrogenase and creatine kinase activities in isolated edema fluid and peripheral blood in cold-induced brain edema. AB - A study of the alterations in lactate dehydrogenase and creatine kinase isoenzyme patterns in isolated grey and white matter edema fluid and in peripheral blood is described with a view to possible clinical use in severe brain-injury. The breakdown of the blood-brain barrier, caused by the infliction of a cold injury to the cerebral cortex of cats, resulted in a shift in the LD isoenzyme distribution in favour of the faster moving fractions and the appearance of brain type CK in the peripheral blood. Total lactate dehydrogenase activity demonstrated no statistical significant changes during the experiment and total creatine kinase showed only slight increased values in the samples collected simultaneously with the infliction of a cold lesion. This strongly suggests that measurements of these parameters in peripheral blood are of little value as indicators of brain damage. Alterations in isoenzyme patterns observed in edema fluids are reflected in peripheral blood. The presence, therefore, of brain-type creatine kinase accompanied by a relative high amount of lactate dehydrogenase H sub unit in peripheral blood, can be considered as adequate indices of severe brain damage. PMID- 6253872 TI - A comparative study of neuromuscular transmission in several mammalian muscular arteries. AB - Intracellular recordings were made from the smooth muscle of isolated segments of the rabbit ear artery, rabbit saphenous artery, rat tail artery, and guinea pig mesenteric artery. Resting membrane potentials recorded from cells in all these arteries were the same (-65 to -75 mV) and perivascular nerve stimulation evoked excitatory junction potentials (EJPs). At stimulation frequencies > 0.2 Hz facilitation of the EJPs was observed in all but the rat tail artery; in this artery the amplitude of the second EJP in a train was less than the first for stimulation frequencies between 0.3 and 2.0 Hz. Spontaneous excitatory junction potentials (SEJPs) at frequencies up to 20/min were recorded during all impalements in the rat caudal artery. In rabbit ear, saphenous and guinea pig measenteric arteries single, supramaximal intensity stimuli evoked EJPs which were not associated with any detectable contraction. Facilitation of EJPs during trains of stimuli > 1 Hz gave rise to graded active responses of up to 50 mV in the saphenous and tail arteries whereas all-or-nothing action potentials of 42- 50 mV were recorded in both the rabbit ear and guinea pig mesenteric arteries. Such responses were always associated with contraction. Intraluminal distension of the arteries had no effect on the RMP or response to nerve stimulation. PMID- 6253873 TI - On the kinetics of the potassium channel activated by acetylcholine in the S-A node of the rabbit heart. AB - 1. Voltage-clamp experiments were conducted on small specimens of rabbit sinoatrial node. In the same preparation the dose-response curve of the potassium current induced by application of different concentrations of acetylcholine (ACh), the time constant of relaxation and the current fluctuations were measured. From these measurements the apparent dissociation constant and the rate constants for the opening and closing of the ACh-activated potassium channel were estimated. 2. In the presence of neostigmine a measurable response was recorded at around 10(-8) M ACh, the saturation was reached at 10(-4) M, and the half saturation was attained at around 10(-6) M. 3. The time constant of relaxation at --35 mV decreased from 100 ms at 10(-8) M to 45 ms at 10(-4) M ACh. 4. The variance of the fluctuations of the ACh-activated current increased with increasing ACh concentration to a peak value of around 10(-5) M. 5. From the above 3 kinds of measurements, opening and closing rate constants of about 12s-1 and 10s-1, respectively, and a dissociation constant of 1.7 microM were calculated. 6. The Katz-Miledi model was considered to be appropriate to describe the reaction of ACh with the muscarinic receptor in the S-A node. 7. The current on ionophoretic application of ACh was computed using the rate constants and taking into account diffusion in the S-A node in which the density of receptors is low. The computed response had a similar time course to the recorded current. PMID- 6253875 TI - Closing of membrane channels effected by gamma-amino-butyric acid (GABA) in crayfish muscle. AB - In a small crayfish muscle fibers current elicited by superfusion of GABA was studied. In the majority of the fibers the GABA induced synaptic current relaxed after voltage steps in agreement with the known voltage and time dependence of the inhibitory chloride channels. In about 20% of the preparations, however, at low GABA concentrations of 5-50 mumol/l an anomalous i--response occurs, namely a reduced total membrane conductance in response to GABA. This i--response can be described by a closing of membrane channels, in which the average closed time increases on hyperpolarization. Equivalent conductance reductions are also observed in measurements of the power spectral density of the current noise. In addition to the noise spectrum of the inhibitory chloride current (Dudel et al. 1980), a spectrum with a higher value of the corner frequency appeared, which seems to represent the i- component. In contrast to the inhibitory chloride current, the i--response is not blocked by picrotoxin. The receptors and channels which mediate the i--response thus seem to be different from those of the inhibitory iCl. Several lines of evidence indicate that the i--response is due to the closing of potassium channels. The i--response counteracts the inhibitory effect of GABA at low GABA concentrations and can distort the dose-response curve. PMID- 6253874 TI - Effect of Na-K-ATPase inhibition on hydrogen ion and potassium secretion. PMID- 6253876 TI - Separation of current induced by potassium accumulation from acetylcholine induced relaxation current in the rabbit S-A node. AB - In a previous analysis on the rabbit S-A node the ACh-induced current was separated from the membrane current by subtracting the control from the current recorded in presence of ACh. In view of a possible interference of K accumulation processes, in the present paper the validity of the subtraction method was tested by studying the direct and indirect effects of ACh on the outward potassium current (iK). The following results were obtained. (1) The ACh-dependent channel activation and the iK-channel activation are different processes. (2) The activation curve of iK and the time constant of decay of iK current on return from a depolarizing clamp pulse were not affected by ACh. (3) In the majority of the experiments the presence of an accumulation component in the extra-current elicited by ACh could not be resolved. In a few cases the amplitude of the tail current was decreased in the presence of ACh. (4) In the case where iK was reduced, the fully-activated current-voltage relationship (i/K) was altered in the same way as that observed when the external K concentration was increased. In this case the difference between the control and the current recorded in the presence of ACh yielded a current component having a time constant similar to that of iK. We concluded that the decrease in the amplitude was due to an increase in K concentration in the clefts between the cells (K accumulation), associated with ACh application. No direct effect of ACh on the iK channel is apparent. (5) Because of the difference in the time constants of the relaxation current and the current change induced by accumulation the two processes could be clearly separated from each other. PMID- 6253877 TI - Increase of adenosine content in cerebral cortex of the cat during bicuculline induced seizure. PMID- 6253878 TI - [Precocious pseudo-puberty due to HCG-secreting androblastoma of the ovary. One case (author's transl)]. AB - A case of ovarian androblastoma (arrhenoblastoma) of the intermediate differentiation type in a 5-year old girl is reported. The clinical features were precocious isosexual puberty with secondary masculinization. The tumour was removed but relapsed 26 months later, requiring ovariectomy and salpingectomy. The patient, who has now been followed up for 7 years and 6 months, is definitely cured. Biochemically, the androblastoma was accompanied by high plasma levels of oestrogens, androgens and, quite exceptionally, human chorionic ganodotropin, alpha HCG and beta HCG. Light and electron microscope examination failed to differentiale Sertoli cells from granulosa cells and Leyding cells from luteinized ovarian stroma cells. Areas resembling syncytiotrophoblastic cells were very limited and could not be seen under the electron microscope. Some cells looked like undifferentiated germ cells. The HCG secreted was biologically active on rabbit ovaries (Reiprich's reaction) but inactive on the girl's contralateral ovary, which was found on two biopsies to be unstimulated and prepubertal. PMID- 6253879 TI - [Combined chemo- and radiotherapy in multiple pulmonary metastases of cylindroma. A preliminary note (author's transl)]. AB - Three patients with bilateral multiple pulmonary metastases of cylindroma were treated with sequential and repeated courses of chemo- and radiotherapy. Objective symptoms of regression were observed. PMID- 6253880 TI - Nucleotide sequence of the EcoRI D fragment of adenovirus 2 genome. AB - The entire nucleotide sequence of the Ad. 2 EcoRI D fragment has been determined using the Maxam and Gilbert method. This sequence of 2678 bp contains informations relative to late mRNAs ending at position 78 and for which an AATAAA sequence corresponding to their 3' ends is found at residue number 833. Position of the PVIII mRNA is determined thus allowing deduction of the probable amino acid sequence of the PVIII protein. The position and the sequence of the first leader of early 3 mRNAs is determined as well as the sequence and position of the second early leader of region 3 mRNAs, which also correspond to the "y" leader of the fiber mRNA. Following the localization of an open reading frame in which an ATG could initiate protein synthesis it can be predicted that 3a, b, c mRNAs code for the 16K early protein and the probable amino acid sequence of this protein can be deduced. The CAGTTT sequence frequently present at the 5' end of a leader or of a mRNA body as well as the GGTGAG sequence which is found at the 3' end of several leaders were used to postulate the position of various early mRNAs of region 3 and to suggest the existence of an additional splicing event during the processing of mRNAs 3a, b and c. They were also used to predict the position of the additional "x" late leaders. The imbrication of information concerning (i) the family of late mRNAs ending at position 78, (ii) the position of the "x" leader and the "y" leader and (iii) the beginning of early region 3 is also depicted. PMID- 6253881 TI - A rapid enzymatic DNA sequencing technique: determination of sequence alterations in early simian virus 40 temperature sensitive and deletion mutants. AB - We have adapted a rapid sequencing technique from the enzymatic nick-translation method of Maat and Smith. The Forward-Backward procedure employs both synthetic and 3' to 5' exonucleolytic activities of E. coli DNA polymerase I to achieve greater reliability, especially in reading stretches of the same nucleotide. The technique has been employed to determine sequence alterations in four early SV40 temperature-sensitive (tsA) point mutants and five early SV40 viable deletion mutants. The nucleotide sequence of these mutants provides an insight into their biological properties. PMID- 6253882 TI - The case of sulfonation in the chemical synthesis of oligonucleotides. AB - The sulfonation of nucleosidic component, a side reaction during phosphotriester bond formation, as a function of the reactivity of the condensing agents and the kind of substituents in the starting phosphodiester is discussed. It was found that in the coupling reaction of nucleoside alkyl phosphodiesters, the degree of sulfonation of the nucleosidic component was very high; while under the same conditions when the aryl group was present in the corresponding phosphodiester, this side reaction practically did not occur. PMID- 6253883 TI - Complete nucleotide sequence of the haemagglutinin gene from a human influenza virus of the Hong Kong subtype. AB - The complete nucleotide sequence has been determined for a cloned double-stranded DNA copy of the haemagglutinin gene from the human influenza strain A/NT/60/68/29C, a laboratory-isolated variant of A/NT/60/68, an early strain of the Hong Kong subtype. The gene is 1765 nucleotides long and contains information sufficient to code for a protein of 566 amino acids, which includes a hydrophobic leader peptide (16 residues), HA1 (328), HA2 (221) and an arginine residue which joins the HA subunits. Comparison of the predicted amino acid sequence for 29C haemagglutinin with protein sequence data available for HA from other influenza strains shows that no potential coding information is lost by processing of the mRNA. A comparison of the amino acid sequences predicted from the gene sequences for 29C and fowl plague virus haemagglutinins, (1) indicates the extent to which changes can occur in the primary sequence of different regions of the protein, while maintaining essential structure and function. PMID- 6253884 TI - HMG proteins (1 + 2) form beaded structures when complexed with closed circular DNA. AB - Structures bearing a resemblance to nucleosomes can be assembled by incubating calf thymus High Mobility Group proteins (1 + 2) with closed circular DNA. These HMG proteins are capable of forming beads and inducing superhelicity when bound to DNA. However, they do not protect from nuclease digestion the discrete DNA fragments characteristic of nucleosomes. The relationship between HMGs (1 + 2) and the "primitive" histone-like DNA-packaging proteins from prokaryotes and mitochondria is discussed. PMID- 6253885 TI - Structure of the host-derived sequences present at the 5' ends of influenza virus mRNA. AB - Nucleotide sequence analysis of the terminal virus-coded regions of a clone of the matrix gene of influenza virus indicated that the region corresponding to the 5' end of the mRNA contains an additional 13 non-virus coded nucleotides. Using the dideoxy-chain termination sequencing method with a restriction fragment derived from this clone, we have determined that the 5' ends of matrix gene mRNAs contain a heterogenous sequence of 9-15 nucleotides. In addition, the data indicate that the 3' terminal nucleotide of matrix gene virion RNA is not transcribed into mRNA, transcription of influenza virus-specific sequences commencing with the penultimate nucleotide at the 3' end of viron RNA. PMID- 6253886 TI - Temporal regulation of herpes simplex virus type 2 transcription and characterization of virus immediate early mRNA's. AB - Nuclear and cytoplasmic virus RNAs, synthesized in cells infected with herpes simplex virus type 2 at early and late times post-infection, and in the continuous presence of the protein synthesis inhibitor cycloheximide (immediate early), have been analyzed by blot hybridization to virus DNA fragments generated by Bam HI and Eco RI restriction endonucleases. Polyadenylated immediate early mRNAs were separated on denaturing gels containing CH3HgOH giving three virus specific mRNA bands of estimated sizes 4.7, 3.4 and 1.75 kb, and these have been mapped to five discrete regions of the genome. The polypeptides produced by in vitro translation of the HSV-2 immediate early mRNA's have been identified. Orientations of immediate early mRNA's on the virus genome have been determined by mapping cDNAs complementary to the 3'termini of the mRNAs. PMID- 6253888 TI - Analysis of DNA double- and single-strand breaks by two dimensional electrophoresis: action of micrococcal nuclease on chromatin and DNA, and degradation in vivo of lens fiber chromatin. AB - We describe a novel system for two dimensional electrophoresis at neutral and alkaline pH for determining the double-stranded and single-stranded lengths of DNA. With this system we analysed the mode of micrococcal nuclease digestion of DNA in cellular and SV40 viral chromatin and of supercoiled SV40 DNA. The enzyme reaction occurred in two steps : the enzyme first introduced single-strand breaks, then converted these to double-strand breaks by an adjacent cleavage on the opposite strand. Digestion of cellular chromatin DNA occurred by a similar mechanism. Chromatin fragments produced by limited micrococcal nuclease action contained many single-strand breaks, which may be important when this method is used to prepare chromatin fragments for biochemical and biophysical studies. Nucleosome monomer to tetramer produced at later stages of digestion contained few if any single-strand breaks. PMID- 6253887 TI - Processing of ribosomal precursor RNAs in Physarum polycephalum. AB - The processing of intermediates of Physarum rRNA has been investigated using two cloned rDNA restriction fragments as sequence specific probes. The size of the largest stable pre-rRNA detected is 11.8 Kb, as determined by denaturing gel electrophoresis. R-loop analysis revealed that this pre-rRNA fraction mainly consists of transcripts which do not contain the two insertion sequences present in the 26 S gene. However, a small number of molecules are found which still contain one or the other, or both, of these introns. These observations suggest that the two introns are transcribed but spliced out in a random order before RNA synthesis has reached the 3-end of the primary transcript. Transcription starts at about 17.7 Kb and stops at 4.4 Kb as measured from the ends of the linear palindromic rDNA molecule. Besides the 11.8 Kb transcript several further ribosomal RNA precursors have been identified, ranging in size from 2.5 to 8.8 Kb. In addition, the genes for 5.8 S RNA have been located by R-loop mapping. PMID- 6253889 TI - Alterations in two conserved regions of promoter sequence lead to altered rates of polymerase binding and levels of gene expression. AB - Characterization of recombinant lac promoters highlights the importance of two regions of sequence conservation in promoters. The "Pribnow box" sequences are necessary for specific transcription in this system. This specificity is maintained when a mutated upstream sequence is introduced. However, changing the upstream DNA sequences influences both the rate of RNA polymerase binding in vitro and levels of expression in vivo. PMID- 6253890 TI - Analysis of recombination in mammalian cells using SV40 genome segments having homologous overlapping termini. AB - Segments of SV40 DNA having homologous overlapping termini recombine to produce viable genomes in monkey cells. Frequencies of recombination on either side of a deletion marker are non-random; replication and palindromes do not appear to be essential. Since recombination involves host enzymes, a suitable system has been devised for analysing host cell recombination functions. PMID- 6253891 TI - Differential nuclease sensitivity of the ovalbumin and beta-globin chromatin regions in erythrocytes and oviduct cells of laying hen. AB - We have monitored the differential nuclease sensitivity of defined regions of the chicken genome in different cells using a method which combines restriction enzyme digestion and blotting to diazobenzyloxymethyl (DBM)-paper (see Ref. 11). By using different specific probes and by scanning the bands on the autoradiograms, it is possible to compare on the same blot the digestion patterns of similar-sized fragments from different regions of the genome corresponding to "active" and reference "inactive" genes. We have demonstrated the preferential sensitivity to DNaseI and micrococcal nuclease digestion of the ovalbumin gene region in hen oviduct chromatin. The beta-globin gene region (containing both an adult and an embryonic gene) is also preferentially digested by DNaseI in hen mature erythrocyte nuclei, but at a lower rate than the ovalbumin gene region in oviduct. These observations raise the possibility that there may be several types of preferential nuclease sensitivities, all characterized by increased rates of digestion but to different levels, the highest corresponding to the very actively transcribing genes. PMID- 6253892 TI - Procollagen mRNA metabolism during the fibroblast cell cycle and its synthesis in transformed cells. AB - Procollagen mRNA was isolated from mouse embryos and used for the synthesis of a highly labelled cDNA probe complementary to collagen mRNA. This probe was used for the investigation of procollagen mRNA metabolism during the cell cycle of 3T6 mouse embryo fibroblasts in culture. Titration hybridization experiments revealed that procollagen mRNA was present throughout the cell cycle following stumulation of confluent monolayers. Procollagen mRNA levels of sparse cultures appeared similar to those of unstimulated monolayers. The fluctuating levels of collagen synthesis during the cell cycle can be ascribed to changes in the amount of collagen mRNA present. In mouse sarcoma virus transformed 3T3 cells only 20--30% of the amount of procollagen mRNA in 3T3 cells is present indicating that the decline in collagen synthesis is due to mRNA availability. PMID- 6253893 TI - Variations in the satellite DNA content of Cucumis melo in relation to dedifferentiation and hormone concentration. AB - Total DNA from Cucumis melo contains a 1.706 satellite DNA which can be resolved into two components; one of these components has a higher temperature of melting (component I) then the other component II). In this study, we have further investigated these components by thermal denaturation and by Eco R1 digestion. Component I reveals a homogeneous melting profile and is only partially cleaved by Eco R1, whereas component II reveals a heterogeneous melting profile and is entirely digested by Eco R1. A possible mitochondrial origin for component II is discussed. When an in vitro culture of root tissues from Cucumis melo was initiated or when the phytohormone (NAA) concentration of established cultures was modified, a new satellite DNA (1.719) appears transitorily and the satellite DNAs already present in seedlings undergo quantitative and possibly qualitative variations. Satellite DNAs therefore seem to be involved in the response to some physiological variations. PMID- 6253894 TI - The release of high mobility group protein H6 and protamine gene sequences upon selective DNase I degradation of trout testis chromatin. AB - Limited digestion of trout testis nuclei with DNase I selectively degrades the protamine genes. Concomitant with the degradation of transcribed DNA sequences a series of chromosomal proteins are released; among these, the major species corresponds to the high mobility group protein H6. The amounts of H6 released from chromatin by limited DNase I action and that in the residual nuclear pellet have been determined. A very high proportion of H6 is associated with DNase I sensitive chromatin regions. PMID- 6253895 TI - Nucleotide sequence encoding the 5' end of Xenopus laevis 18S rRNA. AB - We have sequenced a region of cloned Xenopus laevis ribosomal DNA encompassing the last 24 nucleotides of the external transcribed spacer and the first 275 nucleotides of the 18S gene. The start of the 18S gene was identified by correlating the results obtained from RNA hybridization and fingerprinting with the DNA sequence. This 5' region of 18S rRNA contains five 2'-O-methyl groups and at least six pseudouridine residues. Several of these modified nucleotides are clustered into a relatively short region from nucleotides 99-124. Nucleotides 227 250 constitute a distinctive sequence of 24 consecutive G and C residues. Comparison with the first 160 nucleotides of a yeast 18S gene (25) reveals three blocks of high sequence homology separated by two short tracts where homology is low or absent. The external transcribed spacer sequences diverge widely from within a few nucleotides of the start of the 18S gene. PMID- 6253896 TI - Some characteristics of processing sites in ribosomal precursor RNA of yeast. AB - The DNA sequences of the intergenic region between the 17S and 5.8S rRNA genes of the ribosomal RNA operon in yeast has been determined. In this region the 37S ribosomal precursor RNA is specifically cleaved at a number of sites in the course of the maturation process. The exact position of these processing sites has been established by sequence analysis of the terminal fragments of the respective RNA species. There appears to be no significant complementarity between the sequences surrounding the two termini of the 18S secondary precursor RNA nor between those surrounding the two termini of 17S mature rRNA. This finding implies that the processing of yeast 37S ribosomal precursor RNA is not directed by a double-strand specific ribonuclease previously shown to be involved in the processing of E. coli ribosomal precursor RNA [see Refs 1,2]. The processing sites of yeast ribosomal precursor RNA described in the present paper are all flanked at one side by a very [A+T]-rich sequence. In addition, sequence repeats are found around the processing sites in this precursor RNA. Finally, sequence homologies are present at the 3'-termini [6 nucleotides] and the 5' termini [13 nucleotides] of a number of mature rRNA products and intermediate ribosomal RNA precursors. These structural features are discussed in terms of possible recognition sites for the processing enzymes. PMID- 6253897 TI - Cleavage of DNA.RNA hybrids by type II restriction enzymes. AB - The action of a number of restriction enzymes on DNA.RNA hybrids has been examined using hybrids synthesised with RNAs of cucumber mosaic virus as templates. The enzymes EcoRI, HindII, SalI, MspI, HhaI, AluI, TaqI and HaeIII cleaved the DNA strand of the hybrids (and possible also the RNA strand) into specific fragments. For four of these enzymes, HhaI, AluI, TaqI and HaeIII, comparison of the restriction fragments produced with the known sequences of the viral RNAs confirmed that they were recognising and cleaving the DNA strand of the hybrids at their correct recognition sequences. It is likely that the ability to utilise DNA.RNA hybrids as substrates is a general property of Type II restriction enzymes. PMID- 6253898 TI - Transcriptional mapping of the ribosomal RNA region of mouse L-cell mitochondrial DNA. AB - The map positions in mouse mitochondrial DNA of the two ribosomal RNA genes and adjacent genes coding several small transcripts have been determined precisely by application of a procedure in which DNA-RNA hybrids have been subjected to digestion by S1 nuclease under conditions of varying severity. Digestion of the DNA-RNA hybrids with S1 nuclease yielded a series of species which were shown to contain ribosomal RNA molecules together with adjacent transcripts hybridized conjointly to a continuous segment of mitochondrial DNA. There is one small transcript about 60 bases long whose gene adjoins the sequences coding the 5'-end of the small ribosomal RNA (950 bases) and which lies approximately 200 nucleotides from the D-loop origin of heavy strand mitochondrial DNA synthesis. An 80-base transcript lies between the small and large ribosomal RNA genes, and genes for two further short transcript (each about 80 bases in length) abut the sequences coding the 3'-end of the large ribosomal RNA (approximately 1500 bases). The ability to isolate a discrete DNA-RNA hybrid species approximately 2700 base pairs in length containing all these transcripts suggests that there can be few nucleotides in this region of mouse mitochondrial DNA which are not represented as stable RNA species. PMID- 6253899 TI - The nucleotide sequence of an untranslated but conserved domain at the 3' end of the avian sarcoma virus genome. AB - The genomes of numerous avian retroviruses contain at their 3' termini a conserved domain denoted "c". The precise boundaries and function of "c" have been enigmas. In an effort to resolve these issues, we determined the sequence of over 900 nucleotides at the 3' end of the genome of the Schmidt-Ruppin subgroup A strain of avian sarcoma virus (ASV). We obtained the sequence from a suitable fragment of ASV DNA that had cloned into the single-stranded DNA phage M13mp2. Computer-assisted analysis of the sequence revealed the following structural features: i) the length of "c" - 473 nucleotides; ii) the 3' terminal domain of src, ending in an amber codon at the 5'boundary of "c"; iii) terminator codons that preclude continuous translation from "c"; iv) suitably located sequences that may serve as signals for the initiation of viral RNA synthesis and for the processing and/or polyadenylation of viral mRNA; v) a repeated sequence that flanks src and that could facilitate deletion of this gene; vi) repeated sequences within "c"; and vii) unexplained homologies between sequences in "c" and sequences in several other nucleic acids, including the 5' terminal domain of the ASV genome, tRNATrp and its inversion, the complement of tRNATrp and its inversion, and the 18S RNA of eukaryotic ribosomes. We conclude that "c" probably does not encode a protein, but its sequence may nevertheless serve several essential functions in viral replication. PMID- 6253901 TI - Nucleotide sequence of the gene ompA coding the outer membrane protein II of Escherichia coli K-12. AB - A nucleotide sequence of 2271 basepairs has been determined from cloned E. coli DNA which contains ompA. Withing that sequence, starting at nucleotide 1037, an open translational reading frame encodes a protein of 367 amino acids which starting with amino acid 22 agrees with the primary structure of protein II. The preceeding 21 amino acids constitute a typical signal sequence. There is a non translated region of 360 nucleotides in front of the translational start. The insertion point of an IS1 element 110 nucleotides upstream from the start codon and an amber codon at the position of amino acid residue 28 have been localized in the DNA from two ompA mutants. PMID- 6253900 TI - Protection of (dA.dT) cluster regions in the DNAase I cleavage of DNA by specific interaction with netropsin. AB - The specific DNA binding ligand netropsin selectively blocks dA-dT base pairs in clusters containing two or more consecutive thymine residues at the dNAase I cleavage sites of DNA. Using CD and UV absorption measurements it is shown, that at various ratios of netropsin to nucleotide concentrations and even at satuation of ligand interaction the enzyme cuts along regions containing dG-dC pairs sandwiched between dA-dT pairs. This follows a slow kinetics and is associated with a release of netropsin from those segments. These facts suggests the usefulness of the partial protection of certain DNA sequences in DNAase I cleavage sites in producing DNA fragments in structural studies of the genome. A possible interpretation of the effect of netropsin binding on the enzymatic hydrolysis of phosphodiester bonds of the helix is discussed. PMID- 6253902 TI - The 10 kb Drosophila virilis 28S rDNA intervening sequence is flanked by a direct repeat of 14 base pairs of coding sequence. AB - Most repeat units of rDNA in Drosophila virilis are interrupted in the 28S rRNA coding region by an intervening sequence about 10 kb in length; uninterrupted repeats have a length of about 11 kb. We have sequenced the coding/intervening sequence junctions and flanking regions in two independent clones of interrupted rDNA, and the corresponding 28S rRNA coding region in a clone of uninterrupted rDNA. The intervening sequence is terminated at both ends by a direct repeat of a fourteen nucleotide sequence that is present once in the corresponding region of an intact gene. This is a phenomenon associated with transposable elements in other eukaryotes and in prokaryotes, and the Drosophila rDNA intervening sequence is discussed in this context. We have compared more than 200 nucleotides of the D. virilis 28S rRNA gene with sequences of homologous regions of rDNA in Tetrahymena pigmentosa (Wild and Sommer, 1980) and Xenopus laevis (Gourse and Gerbi, 1980): There is 93% sequence homology among the diverse species, so that the rDNA region in question (about two-thirds of the way into the 28S rRNA coding sequence) has been very highly conserved in eukaryote evolution. The intervening sequence in T. pigmentosa is at a site 79 nucleotides upstream from the insertion site of the Drosophila intervening sequence. PMID- 6253903 TI - Mapping of rRNA genes in an inverted repeat in Nicotiana tabacum chloroplast DNA. AB - Nicotiana tabacum chloroplast DNA contains two copies each of 16S and 23S rRNA genes. These genes are located in an inverted order as determined from restriction fragment mapping and Southern hybridization to restriction fragments. The position of these genes on the N. tabacum chloroplast DNA molecule has been established relative to a complete map of SalI and SMaI restriction enzyme cleavage sites. PMID- 6253904 TI - Cloning and sequence of the cDNA corresponding to the variable region of immunoglobulin heavy chain MPC11. AB - Poly(A)-containing mRNA from mouse myeloma MPC11 was transcribed into cDNA which was cloned in the PstI site of the plasmid pBR322. The transformants were screened by hybridization with a cDNA fragment, derived from plasmid p gamma(11)7, corresponding to the 5' portion of the constant region of MPC11 heavy chain. Several positive transformants were found to contain various lengths of the variable region of the heavy chain. We describe the structure and sequence of one of these clones, pV(11)2, which contains cDNA corresponding to the entire variable region of MPC11 heavy chain and extends to codon 248 in the constant region. The protein sequence deduced from the DNA sequence indicates that the variable region of MPC11 heavy chain contains 121 amino acids and belongs to subgroup II of mouse heavy chains. Comparison of this sequence with other heavy chain sequences suggests a J (joining) segment of 16 residues which overlaps five residues of the third hypervariable region. The cDNA sequence shows that there is no discontinuity between the end of the variable region and the beginning of the constant region. PMID- 6253905 TI - Fine structure of ribosomal RNA. IV. Extraordinary evolutionary conservation in sequences that flank introns in rDNA. AB - By hybridization and DNA sequencing, we have defined a specific region in Xenopus rDNA that is extremely conserved between Tetrahymena, a protozoan, and Xenopus, a vertebrate. This highly conserved region is found at the site where an intron has been shown to interrupt Tetrahymena rDNA [1,2], although we have not detected introns in genomic or cloned Xenopus rDNA. We have noted that the sequences corresponding to nuclear rDNA interon-flanking regions show an intriguing complementarity to tRNAiMet. This suggests possible models for tRNA-rRNA interactions in protein synthesis and/or rRNA splicing. PMID- 6253907 TI - The structure of the covalent linkage between proteins and RNA in encephalomyocarditis virus. AB - Two protein, VPgA and VPgB, are covalently bound to the virion RNA of encephalomyocarditis (EMC) virus. Their molecular weightrs, as determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate are 10,000 and 8,000, respectively. A study of nucleotide-peptides isolated from VPg RNA compound has shown that VPgA is bound to the 5'-terminal nucleotide of RNA by a phosphodiester bond. The 5'-terminal nucleotide of RNA is uridylic acid. It is the hydroxy group of the Tyr residue of VPgA that is involved in the formation of the linkage with RNA. VPgB-RNA seems to be similar to VPgA-RNA both in the structure of the RNA-protein linkage and localization of VPgB on RNA. PMID- 6253906 TI - Secondary structures for splice junctions in eukaryotic and viral messenger RNA precursors. AB - Thermodynamically stable secondary structures have been found for adjacent splice junctions of 17 introns from 10 eukaryotic and viral mRNA precursors. Complementary regions in these structures position the exons to be ligated in a favourable orientation for splicing. The possible role of these structures in a general splicing mechanism in described. PMID- 6253908 TI - A family of moderately repetitive sequences in mouse DNA. AB - When mouse DNA is digested to completion with restriction endonuclease Eco R1, a distinct band of 1.3 kb segments comprising about 0.5-3% of the genome is observed upon agarose gel electrophoresis. This DNA is not tandemly repeated in the genome and is not derived from mouse satellite DNA. Restriction endonuclease analysis suggested that the 1.3 kb segments are heterogeneous. Specific sequences were selected from the 1.3 kb segments and amplified by cloning in plasmid pBR322. Southern transfer experiments indicated that three separately cloned mouse DNA inserts hybridized predominantly to the Eco R1 1.3 kb band and to the conspicuous subsegments generated by secondary restriction endonuclease cleavage of the sucrose gradient purified 1.3 kb segments. Segments were also excised by Hha I (Hha I segments) from the chimeric plasmids containing mouse DNA inserts and subjected to restriction endonuclease and cross-hybridization analysis. It was found that the three Hha I segments were different, although two of them exhibited partial sequence homology. Cot analysis indicated that each of the Hha I segments are repeated about 10(4) times in the mouse genome. These findings indicate that a family of related but non-identical, moderately repetitive DNA sequences, rather than a single homogeneous repeat, is present in the 1.3 kb Eco R1 band. PMID- 6253909 TI - Analysis of the regions flanking the human insulin gene and sequence of an Alu family member. AB - The regions around the human insulin gene have been studied by heteroduplex, hybridization and sequence analysis. These studies indicated that there is a region of heterogeneous length located approximately 700 bp before the 5' end of the gene; and that the 19 kb of cloned DNA which includes the 1430 bp insulin gene as well as 5650 bp before and 11,500 bp after the gene is single copy sequence except for 500 bp located 6000 bp from the 3' end of the gene. This 500 bp segment contains a member of the Alu family of dispersed middle repetitive sequences as well as another less highly repeated homopolymeric segment. The sequence of this region was determined. This Alu repeat is bordered by 19 bp direct repeats and also contains an 83 bp sequence which is present twice. The regions flanking the human and rat I insulin genes were compared by heteroduplex analysis to localize homologous sequences in the flanking regions which could be involved in the regulation of insulin biosynthesis. The homology between the two genes is restricted to the region encoding preproinsulin and a short region of approximately 60 bp flanking the 5' side of the genes. PMID- 6253910 TI - Equilibrium melting of plasmid ColE1 DNA: electron-microscopic visualization. AB - The fine structure of the melting curve for the linear colE1 DNA has been obtained. To find the ColE1 DNA regions corresponding to peaks in the melting curve's fine structure, we fixed the melted DNA regions with glyoxal /12/. Electron-microscopic denaturation maps were obtained for nine temperature points within the melting range. Thereby the whole process of colE1 DNA melting was reconstructed in detail. Spectrophotometric and electron microscopic data were used for mapping the distribution of Gc-pairs over the DNA molecule. The most AT rich DNA regions (28 and 37% of GC-pairs), 380 and 660 bp long resp., are located on both sides of the site of ColE1 DNA's cleavage by EcoR1 endonuclease. The equilibrium denaturation maps are compared with maps obtained by the method of Inman /20/ for eight points of the kinetic curve of ColE1 DNA unwinding by formaldehyde. PMID- 6253911 TI - Spin-labeled polyribonucleotides. AB - Poly (U), poly (C) and poly (A) were spin labeled with N-(2,2,5,5-tetramethyl-3 carbonylpyrroline-1-oxyl)-imidazole. This spin label interacts selectively with 2' OH ribose groups of polynucleotides and does not modify the nucleic acid bases. The extent of spin labeling is not dependent upon the nature of the base and is entirely determined by rigidity of the secondary structure of the polynucleotide. The extent of modification for poly (U), poly (C) and poly (A) was 4.2, 1.7 and 1.5 per cent, respectively, the secondary structure of the polynucleotides being practically unchanged. Some physico-chemical properties of the spin-labeled polynucleotides were investigated by ESR spectroscopy. Rotational correlation times of the spin label and activation energy of its motion were calculated. PMID- 6253912 TI - Involvement of DNA gyrase in the transcription of ribosomal RNA. AB - The DNA gyrase inhibitor novobiocin specifically inhibits the transcription of ribosomal RNA in vivo while protein synthesis and the mRNA transcription are only partly affected. In vitro the novobiocin inhibition is only observed when protein fraction, which stimulates ribosomal RNA synthesis, is present. These results indicate that DNA gyrase is involved in the transcription of ribosomal RNA, probably at an initiation step. PMID- 6253913 TI - Fusion of the promoter region of rRNA operon rrnB to lac Z gene. AB - A Lambda phage was constructed in which the structural gene for beta galactosidase is fused to a DNA segment carrying the ribosomal promoter rrnB of E. coli. In this hybrid operon beta galactosidase synthesis in vitro is repressed by ppGpp. Repression of beta galactosidase synthesis by cAMP is reported. PMID- 6253914 TI - Molecular structure of the immunity gene and immunity protein of the bacteriocinogenic plasmid Clo DF13. AB - The nucleotide sequence of the Clo DF13 DNA region comprising the immunity gene has been determined. We also elucidated the aminoacid sequence of the 40 N terminal and 7 C-terminal aminoacids of the purified immunity protein. From analysis of the data obtained we were able to locate the immunity gene between 11.7 and 14.5% on the Clo DF13 map, and to determine the complete aminoacid sequence of the immunity protein. It was observed that the Clo DF13 immunity gene encodes an 85 aminoacid protein and is transcribed in the same direction as the cloacin gene. These experimental data support our model, presented elsewhere, which implicates that the cloacin and immunity genes of Clo DF13 are coordinately transcribed from the cloacin promoter. We also present DNA sequence data indicating that an extra ribosome binding site precedes the immunity gene on the polycistronic mRNA. This ribosome binding site might explain the fact that in cloacinogenic cells more immunity protein than cloacin is synthesized. The comparison of the complete aminoacid sequence of the Clo DF13 immunity protein, with the aminoacid sequence data of the purified, comparable Col E3 immunity protein revealed that both proteins have extensive homologies in primary and secondary structure, although they are exchangeable only to a low extent in vivo and in vitro. It was also observed that a lysine residue was modified in immunity protein isolated from excreted bacteriocin complexes. PMID- 6253915 TI - Initiation of polyoma virus DNA replication in vitro and its dependence on the viral gene A protein. AB - Initiation of polyoma virus DNA replication is dependent on the activity of the early protein affected by the tsa mutations (large-T antigen). An in vitro DNA synthesizing system blocked at the initiation stage was designed by preparing nuclei from cells shifted to high temperature after infection with a polyoma tsa mutant. Addition to these nuclei of extracts from wild type virus-infected cells resulted in a limited, but reproducible stimulation of deoxynucleoside monophosphate incorporation. At least for a significant part, this stimulation was shown to correspond to an increased synthesis of molecules identified as polyoma replicative intermediates by their sedimentation coefficient and endonuclease Hpa II cleavage pattern. The non-random distribution of label observed among restriction fragments was that expected from an initiation event occuring at the physiological origin. This activity was reduced to background level in extracts from tsa-infected cells shifted to high temperature and was specifically inhibited by addition of Fab fragments from anti-polyoma virus T antigen immunoglobulins. PMID- 6253916 TI - The 5' flanking region of human epsilon-globin gene. AB - The structural analysis of the 2.0 kb region upstream from the epsilon-globin gene has been carried out. A genomic DNA map around the gene was worked out in some detail to ensure that the cloned DNA was representative of the actual chromosomal arrangement. Furthermore, a new technique was developed to precisely map a reiterated DNA sequence present 1.5 kb to the 5' side of the gene. The complete nucleotide sequence of the 2.0 kb 5' flanking region was then determined and overlapped with the gene. The sequence included the reiterated DNA sequence which is homologous to the so-called AluI family of repeats. Unusual stretches of sequence 50 nucleotides long, where A + T represent about 90% of the bases, are present at both the 5' and 3' sides of the repeat. PMID- 6253917 TI - A detailed comparison of the 5'-end of the ovalbumin gene cloned from chicken oviduct and erythrocyte DNA. AB - We have examined homologous fragments of DNA cloned from two different tissues for changes in the dNA sequence which might be related to tissue specific gene expression. The 5' end of the chicken ovalbumin gene was cloned from oviduct or erythrocyte DNA DNA using cosmids as vectors. We have compared the two clones obtained by restriction enzyme digestions, analysis of heteroduplexes by electron microscopy or S1 nuclease digestion and by DNA sequencing. Our results show that whereas no alteration occured in the region of the gene assumed to be of importance for the control of transcription, a 4 nucleotide deletion/insertion was detected in the first intron of the ovalbumin gene. PMID- 6253918 TI - The baboon endogenous virus genome. II. Provirus sequence variations in baboon cell DNA. AB - Restriction analysis of the approximately 100 integrated baboon endogenous virus (BaEV) proviruses in baboon cells and tissues has revealed two major sequence variations, both in the gag gene region of the genome. One, a 150 nucleotide pair insert, is present in a small proportion of the proviral DNAs and some baboons, but is present in the majority of the proviral DNAs of other baboons. The second, a Bam HI recognition sequence located 2.25 kb from the proviral 5' end, is missing or modified in approximately one-half of the integrated genomes. We consider the possibility that accumulation of proviruses not containing the 0.15 kb insert is correlated with viral activation and expression since it is this form that is a replication intermediate in freshly infected permissive cells. It is evident from these initial studies that the organization of the multiple BaEV proviruses in baboon DNA has undergone modification during evolution. PMID- 6253920 TI - Fine structure mapping of an avian tumor virus RNA by immunoelectron microscopy. AB - The RNA of a deleted strain (lacking Src gene) of an avian sarcoma virus (ASV) was examined by a newly developed immunoelectron microscopic procedure which uses anti-nucleotide antibodies as probes. After denaturation of the RNA and reaction with a high affinity, highly specific anti-7-methylguanosine-5'-phosphate (anti pm 7G), 81% of 106 molecules examined were found to have antibody at one terminus, in agreement with the presence of a pm 7G cap in ASV-RNA. Hapten inhibition by pm 7G could be demonstrated. Experiments with anti-A and with anti poly A gave results consistent with the known structure of ASV-RNA, in particular the presence of a 3' poly A tail. These studies illustrate the feasibility of using anti-nucleotide antibodies in a combined immunochemical and electron microscopic study of the fine structure of nucleic acids. PMID- 6253919 TI - Four Drosophila heat shock genes at 67B: characterization of recombinant plasmids. AB - A 33 kilobase region of the 67B locus of Drosophila melanogaster genome has been isolated. The genes for the 27K, 26K, 23K and 22K heat shock induced proteins are contained within an 11 kb segment. the 27K gene, approximately 1.4 kb in length, and the 23K gene, approximately 1.0 kb in length, are separated by about 1.5 kb of spacer DNA; a third block of transcription, which encodes the 26K gene, is approximately 1.1 kb in length, and is separated from the gene for the 23K protein by 4.5 kb of spacer DNA. The 22K gene is located approximately 1.2 kb from the 26K gene. The RNAs encoding the 27K, 23K and 22K genes are transcribed from the same DNA strand. With the assignment of the four small heat shock induced proteins to 67B, genes for all seven major heat shock induced proteins have no been mapped cytologically. PMID- 6253921 TI - An Escherichia coli endonuclease responsible for primary cleavage of in vitro transcripts of bacteriophage T4 tRNA gene cluster. AB - An endonuclease activity was isolated from 100,000 g supernatant fraction of Escherichia coli using in vitro primary transcripts of T4 tRNA gene cluster as assay substrates. The endonuclease cleaves the polycistronic RNA precursors into fragments containing monomeric and dimeric stable RNA sequences. The result strongly suggest that this enzyme participates in the early steps of T4 tRNA maturation pathway preceding the action of RNase P. PMID- 6253922 TI - Origin and direction of replication in mitochondrial DNA molecules from the genus Drosophila. AB - Mitochondrial DNA (mtDNA) obtained from ovaries of Drosophila simulans, D. mauritiana, D. takahashii, D. yakuba and D. virilis was examined by electron microscopy. From a consideration of the structural properties of replicative intermediates, it was concluded that in mtDNA molecules of each species, synthesis on one strand can be up to 97% complete before synthesis on the complementary strand is initiated. MtDNA molecules of each species contain a single A+T-rich region which shows species-specific size variation from 1.0 kb (D. virilis) to 4.8 kb (D. simulans), and maps at the same position in all molecules relative to three common EcoRI sites. The structural properties of complex forms, interpreted as having originated from replicative intermediates, and produced by either partial denaturation or EcoRI digestion, are consistent with the hypothesis that replication is initiated within the A+T-rich region and proceeds unidirectionally around the molecule towards the nearest common EcoRI site. The replication origin is located near the center of the A+T-rich region in D. simulans and D. mauritiana, but lies closer to that end of the A+T-rich region which is distal to the nearest common EcoRI site in D. takahashii, D. yakuba and D. virilis. PMID- 6253923 TI - Interaction of the cAMP receptor protein with the lac promoter. AB - The cyclic AMP receptor protein (CRP) stimulates transcription of the lactose operon by binding to the lac promoter. I have identified those 5-positions of thymines in the promoter that lie close to bound CRP. Although ultraviolet irradiation of DNA with 5-bromouracil substituted in place of thymine normally cleaves the DNA at the bromouracils, a protein bound to the DNA can perturb these cleavages at those locations at which the protein lies close to the bromine. The contacts inferred from this photochemical probe and the results of nucleolytic attack of this complex by exonuclease III support a model where the cyclic AMP receptor protein binds to the promoter making symmetrical contacts with one face of the double helix and then stimulates transcription through contacts with RNA polymerase. PMID- 6253924 TI - The specific organisation of satellite DNA sequences on the X-chromosome of Mus musculus: partial independence of chromosome evolution. AB - DNA was isolated from a chinese hamster/mouse hybrid cell line containing a single mouse chromosome, the X-chromosome, and digested with a variety of restriction endonucleases known to cut mouse satellite DNA. After agarose gel electrophoresis and transfer to nitrocellulose, hybridisation was carried out to a radioactive mouse satellite DNA probe. In this manner the organisation of satellite sequences at an individual chromosome was determined. We have found that the organisation of centromeric satellite DNA sequences on the mouse X chromosome differs from that of other chromosomes in the complement. The nature of the differences suggests features of evolution of highly repeated sequences within a karyotype. PMID- 6253925 TI - The organization of the ribosomal RNA genes in the fungus Mucor racemosus. AB - The rDNA of Mucor racemosus is contained on a 6.4 megadalton repeat unit. Two Bam H-1 restriction fragments that encompass the entire rDNA repeat, as well as two Hind III restriction fragments that lie within the region, have been cloned and analyzed. The rDNA unit has been defined with respect to eight restriction endonucleases and the position of the sequences encoding the 25S, 18S, and 5.8S rRNA species have been localized. In addition, the 55 RNA encoding sequence was found to reside within the basic repeat unit. The results indicate the organization of the rDNA of Mucor more closely resembles the arrangement observed in yeast than that observed in other eukaryotic organisms. PMID- 6253926 TI - DNA gyrase stimulates transcription. AB - The nuclear DNA of HeLa cells can now be isolated unbroken and supercoiled. Using DNA gyrase and the untwisting enzyme, we have prepared an allomorphic series of templates derived from this nuclear DNA, and also from the circular DNA of the bacterial virus, PM2. We have then transcribed these templates using 2 different RNA polymerases--from wheat germ and Escherichia coli. Relaxed DNA is transcribed slowly by both polymerases. Supertwisting the naturally-supercoiled templates with gyrase slightly inhibits transcription by the bacterial polymerase but stimulates dramatically transcription by RNA polymerase II from wheat germ. PMID- 6253927 TI - The nucleotide sequence and restriction enzyme sites of the polyoma genome. AB - We present the 5295 nucleotide-long sequence of the polyoma genome and the restriction enzyme digestion sites predicted from this sequence. PMID- 6253928 TI - The presence of nuclear and mitochondrial uracil-DNA glycosylase in extracts of human KB cells. AB - Extracts of human KB cells contain detectable uracil-DNA glycosylase activity. The majority of the activity is located within the nuclear fraction, however we present evidence for the presence of identifiable uracil-DNA glycosylase activity associated with the mitochondrial fraction of these cells. PMID- 6253929 TI - Organization of 5S genes in chromatin of Xenopus laevis. AB - The chromatin organization of the genes coding for 5S RNA in Xenopus laevis has been investigated with restriction endonucleases and micrococcal nuclease. Digestion of nuclei from liver, kidney, blood and kidney cells maintained in culture with micrococcal nuclease reveals that these Xenopus cells and tissues have shorter nucleosome repeat lengths than the corresponding cells and tissues from other higher organisms. 5S genes are organized in nucleosomes with repeat lengths similar to those of the bulk chromatin in liver (178 bp) and cultured cells (165 bp); however, 5S gene chromatin in blood cells has a shorter nucleosome repeat (176 bp) than the bulk of the genome in these cells (184 bp). From an analysis of the 5S DNA fragments produced by extensive restriction endonuclease cleavage of chromatin in situ, no special arrangement of the nucleosomes with respect to the sequence of 5S DNA can be detected. The relative abundance of 5S gene multimers follows a Kuhn distribution, with about 57% of all HindIII sites cleaved. This suggests that HindIII sites can be cleaved both in the nucleosome core and linker regions. PMID- 6253930 TI - Complete nucleotide sequence of a cloned chicken alpha-globin cDNA. AB - Chicken globin double-stranded cDNA was synthesised from anaemic adult reticulocyte alpha- and beta-globin mRNA and ligated into the Hind III site of pBR322 using synthetic Hind III decamers. Transformation of E. coli x1776 resulted in the production of a number of alpha- and beta-cDNA clones. One of the alpha-type clones (pCG alpha-8) was fully sequenced and found to code for neither alpha A- nor alpha D-globin. Partial sequencing of the other alpha-cDNA clones indicates that they are all of the same type. PMID- 6253931 TI - The structure of poliovirus replicative form. AB - The structure of polio replicative form (RF) has been investigated by 3' end labeling and the use of polynucleotide phosphorylase to now allow a complete composite of the RF structure. The evidence presented indicates that the 3' terminal sequence of the minus strand is an exact complement to the 5' end of polio RNA. This suggests that the 5' terminal U of polio RNA is genetically coded. Other data is presented to show that in addition to the genetically coded poly(A) tract of the plus strand in RF, a single-stranded poly(A) tail protrudes beyond the double-stranded RNA. PMID- 6253932 TI - Mouse immunoglobulin genes: a bacterial plasmid containing the entire coding sequence for a pre-gamma 2a heavy chain. AB - A DNA sequence complementary to the entire coding part of a mouse gamma 2a immunoglobulin heavy chain mRNA isolated from a myeloma producing a levan binding protein (UPC 10), has been cloned in the PstI site of pBR 322. Transformants containing sequences complementary to purified gamma 2a heavy chain mRNA were selected. One transformant, pG2a-10-21, containing a 1750 nucleotide insert, has been characterized by hybrid-arrested translation and purification of gamma 2a heavy chain mRNA on DNA-DBM cellulose filters. Restriction enzyme analysis and partial sequencing demonstrate that the pG2a-10-21 contains the complete structural sequence for the gamma 2a heavy chain and predicts the sequence of a 18 amino acid hydrophobic amino terminal extra piece segment. PMID- 6253933 TI - Clusters containing different mobile dispersed genes in the genome of Drosophila melanogaster. AB - Ten clones containing the actively transcribed mobile dispersed gene Dm255 and its flanking sequences were selected from the HindIII bank of the Drosophila melanogaster genome. The Dm225 sequences present in these clones were identical while the flanking sequences were different in all of the clones analysed. Four of them contained, in addition to Dm225, other DNA sequences binding high amounts of cytoplasmic poly(A) + RNA. The properties of these new genes are similar to those of Dm255: they are also actively transcribed, multiple in copies, scattered throughout the genome, and located at varying genome sites which also were scattered throughout the whole genome of D. melanogaster. Thus, different mobile dispersed genes often appear as closely apposing units forming gene clusters in the genome. PMID- 6253934 TI - Endonucleases for UV-irradiated and depurinated DNA in barley chloroplasts. AB - Lysates of barley chloroplasts release more radioactivity into acid soluble form from UV-irradiated and alkylated-depurinated E. coli [3H] DNA than from intact DNA. By means of affinity chromatography on depurinated DNA-cellulose and/or UV irradiated DNA-cellulose and by electrophoresis in polyacrylamide gels, four activities on depurinated DNA were separated. One of these contained activity against heavily UV-irradiated /270 J.m-2/ native DNA. In addition, two other nucleases specific towards UV-DNA were separated. One of them was active on native and heat denatured DNA irradiated with 10 J . m-2 UV, whereas the other was predominantly active on native UV-irradiated DNA. PMID- 6253935 TI - Nucleotide sequence of the mitochondrial genes coding for tRNAglyGGR and tRNAvalGUR. AB - Yeast mitochondrial DNA-pBR322 recombinant DNA molecules known to contain tRNA genes from a tRNA rich region of the yeast genome were used as a source of DNA for restriction mapping and tRNA gene sequence analysis. We report here restriction maps of two segments of yeast mitochondrial DNA and the sequence of mitochondrial genes coding for tRNAglyGGR and tRNAvalGUR. Both genes are flanked by A + T rich DNA and neither has an intervening sequence nor codes for a 3' CCA end. The tRNA structures deduced from the genes have the usual cloverleaf structures and invariant nucleotides. This combination of DNA sequencing and restriction mapping has enabled us to determine that the tRNAvalGUR and a previously sequenced tRNA, the tRNApheUUY are transcribed from the same strand of DNA. PMID- 6253936 TI - The nucleotide sequence surrounding the replication origin of the cop3 mutant of the bacteriocinogenic plasmid Clo DF13. AB - The nucleotide sequence from about 100 base-pairs downstream to about 600 base pairs upstream the CloDF13 replication origin has been determined. A comparison of this sequence with the corresponding ColE1 origin sequence reveals that: The sequence at the origin of replication is conserved. There are large differences in the nucleotide sequence downstream the replication origin, whereas there is a large homology in the region of about 410 base-pairs upstream the replication origin. This conserved region might code for a largely homologous basic, arginine rich polypeptide of about 45 amino-acids, for both ColE1 and CloDF13. Although there are large differences in the primary structure of the region coding for the 100 nucleotide RNA, the secondary structure of this region seems to be conserved. PMID- 6253937 TI - Variable patterns of total DNA and rDNA methylation in animals. AB - Restriction endonucleases were used to determine the degree of methylation at the sequences CCGG and GCGC in a wide range of animal DNAs. Both total DNA methylation and ribosomal DNA methylation were studied. Whole DNA methylation was indetectable in arthropods, fractional in other invertebrate phyla, and high in the vertebrates. Ribosomal DNA was predominantly unmethylated in all animals except fish and amphibia, where it was heavily methylated. We discuss the evolutionary and functional implications of these results, and suggest that the large differences between genome types are the result of evolutionary changes in the relative size of heavily methylated and unmethylated compartments. PMID- 6253938 TI - DNA methylation and the frequency of CpG in animal DNA. AB - An analysis of nearest neighbour dinucleotide frequencies and the level of DNA methylation in animals strongly supports the suggestion that 5-methylcytosine (5mC) tends to mutate abnormally frequently to T. This tendency is the likely cause of the CpG deficiency in heavily methylated genomes. PMID- 6253939 TI - Electron microscopic demonstration of the presence of amplified sequences at the 5'-ends of the polyoma virus late mRNAs. AB - Electron microscopic techniques were used to examine the structure of the leader sequences at the 5'-ends of the late polyoma virus mRNAs. The three late mRNA's were partially purified and hybridized to an E. coli plasmid containing two polyoma virus genomes inserted in tandem. The hybrids were spread by the cytochrome c-formamide technique and visualized in the electron microscope. These studies revealed that whereas the body of a given mRNA molecule can hybridize with only one of the two corresponding body sequences in the two adjacent viral genomes, the leader of the same mRNA molecule can hybridize with both copies of the leader sequence-specific DNA. The mVP1 and mVP3 RNA species thus generated hybrids containing two loops, while mVP2 molecules formed hybrids containing one loop. Hence, the leaders of the three polyoma virus late mRNA species must contain two or more repeats of a sequence transcribed from a unique DNA segment. Length measurements showed that most leaders in the late mRNA's consist of at least 200 nucleotides and some contain up to 500 nucleotides, whereas the basic repeat sequence contains about 60 nucleotides. PMID- 6253941 TI - Purification and characterization of an endonuclease specific for apurinic sites in DNA from a permanently established mouse plasmacytoma cell line. AB - An endonuclease specific for apurinic sites in double stranded DNA has been purified 373-fold from the nuclei of mouse plasmacytoma cells (line MPC-11). The enzyme is free of any detectable amounts of aspecific nucleases. The enzyme does not act on methylated or OsO4-treated DNA. However, high doses of UV-light and gamma-rays render the DNA slightly susceptible to endonucleolytic attack, which is believed to be due to depurination of depyrimidination caused by the treatment. The molecular weight of the enzyme is determined to be 28,000 and its apparent Km of the purified enzyme is calculated to be 2.7 nM apurinic sites. The activity is not absolutely dependent upon the presence of Mg2+ in the assay mixture although metal chelating agents such as sodium citrate and EDTA abolish the activity completely. The nuclease was stimulated by moderate concentrations of potassium chloride optimizing at 50 mM, and higher concentrations inhibiting the activity. The pH optimun for the reaction was 9.5. PMID- 6253940 TI - Structure of a promotor on plasmid pMB9 derived from plasmid pSC101. AB - The DNA sequence of a 354 basepair EcoRI-HindIII fragment of plasmid pMB9 which has originally been derived from plasmid pSC101 has been resolved. This fragment contains a promoter for transcription directed towards the EcoRI site. Escherichia coli RNA polymerase binds to a region within the EcoRI-HindIII fragment which contains the heptamer 5' TATGGTG (132-126) and the duodecamer 5' TGATGAACATCA (158-147). Based on commonalities with other promotors these DNA sequences probably function as, respectively, "binding site" and "recognition site". Furthermore, this fragment harbours a translation reading frame free of nonsense codons and at about 25 basepairs from the indicated heptamer a nucleotide sequence which meets with the requirements for initiation of translation. By heteroduplex mapping it was shown that the EcoRI-HindIII fragment has been derived from a region near or within the origin of replication of pSC101. The copynumber of plasmids containing the EcoRI-HindIII fragment is two fold lower than that of plasmids lacking this fragment. This effect might be related to the original function of this fragment on plasmid pSC101. PMID- 6253944 TI - A rearranged DNA sequence possibly related to the translocation of immunoglobulin gene segments. AB - A 5.3 kb EcoRI fragment (T3, abbreviations in ref. 2) has been cloned from DNA of a kappa light chain producing mouse myeloma. The fragment hybridizes to the k' flanking sequences of the J1 gene segment but not to C gene sequences of kappa light chain DNA. Restriction nuclease mapping and partial nucleotide sequencing showed that the fragment consists of sequences from the 5' side of the J1 and form the 3' side of a V gene segment, which apparently had been linked in a genomic rearrangement process. These rearranged flanking sequences are not the flanking sequences of the V and J gene segments which had been joined to form the two kappa light chain genes of the myeloma. Fragments with the hybridization properties of T3 have been found also in two other kappa and one lambda chain producing myelomas. The linking of flanking sequences in the myeloma genome is discussed with respect to the mechanism of recombination between V and J gene segments. PMID- 6253942 TI - Replication of herpes simplex virus type I DNA in permeabilized infected cells. AB - Herpes simplex type 1 (HSV)-infected Vero cells can be permeabilized by a combination of hypotonic shock and a mild emulsifier, gum arabic. Permeabilized cells will incorporate triphosphate precursors into viral and host DNA in vitro in ratios similar to those seen in vivo. This reaction is ATP-dependent and is shown to be replicative by the single strand density shift of DNA synthesized in the presence of BrdUTP. The product is heterogeneous in size, and contains a significant proportion of rapidly sedimenting forms and of unit size (55S) viral DNA. The presence of polyamines and EGTA (a specific chelator of Ca2+ ions) in the labeling medium is shown to be necessary to maintain the integrity of the replicating DNA. The average size of newly synthesized single strands, however, is smaller than seen in vivo. The reaction is sensitive to phosphonoacetic acid added at the time of labeling, at concentrations which inhibit in vivo synthesis only after one hour of pre-exposure. These properties make permeabilized cell monolayers an attractive system for the study of HSV DNA replication. PMID- 6253943 TI - Two rearranged immunoglobulin kappa light chain genes in one mouse myeloma. AB - The organization of immunoglobulin gene segments coding for kappa light chains has been studied in uncloned and cloned DNA from mouse liver and a mouse myeloma. It is known that the C (constant, ref. 2) gene segment is present in the tumor DNA on two EcoRI fragments of 14 and 20 kb and in liver DNA on a 15 kb fragment. The 14 kb myeloma and the 15 kb liver fragment have been cloned previously. Here we report on the cloning of the 20 kb myeloma fragment and present detailed restriction maps covering about 22 kb of DNA surrounding the C gene segment in liver and tumor DNA. The region on the 20 kb fragment has been localized where a DNA rearrangement had occurred. The presence of two rearranged kappa light chain genes in one tumor is discussed in regard to the molecular basis of allelic exclusion. PMID- 6253945 TI - Cloning of V region fragments from mouse liver DNA and localization of repetitive DNA sequences in the vicinity of immunoglobulin gene segments. AB - Two different kappa light chain genes have previously been isolated from one mouse myeloma. The V (variable, abbreviations in ref. 2) gene segments of the two genes were now used to identify their germline counterparts in EcoRI digests of mouse liver DNA. In addition two sets of related V gene segments were found which hybridize with either of the two DNA probes. Five of the V region fragments of one set were cloned in a lambda phage vector and partially characterized by restriction mapping and Southern blot hybridization. Repetitive DNA sequences were found on each of the five fragments as well as on other cloned immunoglobulin gene containing fragments. Cross-hybridization between some but not all of the regions containing repetitive DNA sequences was observed. PMID- 6253946 TI - A short primer for sequencing DNA cloned in the single-stranded phage vector M13mp2. AB - In this paper we describe the synthesis and cloning of a short segment of DNA complementary to the region immediately adjacent to the EcoRI insertion site in the single-stranded bacteriophage vector M13mp2. This segment is useful as a "universal" primer for DNA sequencing by the dideoxynucleotide chain termination method; the template can be any DNA species cloned in M13mp2 or its derivatives. The primer has been cloned into the tetracycline resistance gene of plasmid pBR322 as one strand of a 26 bp EcoRI/BamHI fragment. This fragment may be readily prepared from an EcoRI + BamHI restriction digest of the parent plasmid (designated pSP14) by a simple size fractionation. PMID- 6253947 TI - DNA sequence of the int-xis-Pi region of the bacteriophage lambda; overlap of the int and xis genes. AB - The DNA sequence of the int and xis genes of lambda bacteriophage, as well as that of the PI promoter and a region of unknown function beyond this, was determined by the chain termination procedure. The Pribnow box sequence of the PI promoter lies just within the xis gene, and both possible sites of mRNA initiation from PI are within the xis gene. The end of the xis gene in its turn overlaps the start of the int gene by 23 base pairs, in a different reading frame. This overlap may play a role in ensuring efficient excision of the prophage in response to natural induction signals. PMID- 6253948 TI - Studies on the biological role of dna methylation; IV. Mode of methylation of DNA in E. coli cells. AB - Two pairs of restriction enzyme isoschizomers were used to study in vivo methylation of E. coli and extrachromosomal DNA. By use of the restriction enzymes MboI (which cleaves only the unmethylated GATC sequence) and its isoschizomer Sau3A (indifferent to methylated adenine at this sequence), we found that all the GATC sites in E. coli and in extrachromosomal DNAs are symmetrically methylated on both strands. The calculated number of GATC sites in E. coli DNA can account for all its m6Ade residues. Foreign DNA, like mouse mtDNA, which is not methylated at GATC sites became fully methylated at these sequences when introduced by transfection into E. coli cells. This experiment provides the first evidence for the operation of a de novo methylation mechanism for E. coli methylases not involved in restriction modification. When the two restriction enzyme isoschizomers, EcoRII and ApyI, were used to analyze the methylation pattern of CCTAGG sequences in E. coli C and phi X174 DNA, it was found that all these sites are methylated. The number of CCTAGG sites in E. coli C DNA does not account for all m5Cyt residues. PMID- 6253950 TI - Precursors to 16S and 23S ribosomal RNA from a ribonuclear III-strain of Escherichia coli contain intact RNase III processing sites. AB - Escherichia coli cells lacking the ribosomal RNA processing enzyme RNase III do no excise the normal RNA precursors p16a (17S) and p23a from nascent rRNA transcripts. These cells produce, instead, slightly larger p16b and p23b precursors. Digestion of p16b or p23b rRNA with RNases A plus T1 yields double stranded fragments composed of sequences, located at both the 5' and the 3' end regions of the molecules. The terminal duplex, or stem, of p16b contains sequences surrounding the site of RNase III processing which is wild-type cells produces p16a rRNA: the p23b stem likewise contains an intact RNase III cleavage site. The results confirm our earlier prediction for the structure of rRNA transcripts, and also yield a definite secondary structure for the p16 stem, which was not uniquely determined by the corresponding DNA sequence. These experiments demonstrate the absence of significant RNase III processing activity in rnc-105 strains of E. coli, and implicate the participation of another endonuclease(s) in rRNA processing in mutant and wild-type cells. PMID- 6253949 TI - Nucleotide sequence of a 5S ribosomal RNA gene in the sea urchin Lytechinus variegatus. AB - The nucleotide sequence of a cloned DNA fragment corresponding to a gene for 5S ribosomal RNA from the sea urchin Lytechinus variegatus has been determined. This sequence is representative of the dominant species of 5S rRNA labelled in vivo with 32pO4 during the cleavage stage of Lytechninus embryonic development. PMID- 6253951 TI - Nucleotide sequences at the ends of the mercury resistance transposon, Tn501. AB - The nucleotide sequences at the ends of the mercury-resistance transposon, Tn501, have been determined. The terminal sequences are inverted repeated sequences 38 nucleotide pairs in length, which differ in 3 nucleotide pairs. The transposon is flanked by directly repeated sequences of 5 nucleotide pairs, originating from a single pentanucleotide sequence in the recipient replicon. There is no obvious homology between recipient replicons at the site of insertion of the transposon. The structures of the ends of Tn501 are compared with those of other transposons and insertion sequences. The use of Tn501 to locate an EcoRI site within a genetically defined sequence of interest is discussed. PMID- 6253953 TI - Studies of the recognition sequence of phi X174 gene A protein. Cleavage site of phi X gene A protein in St-1 RFI DNA. AB - It is already known that phi X gene A protein converts besides phi X RFI DNA also the RFI DNAs of the single-stranded bacteriophages G4, St-1, alpha 3 and phi K into RFII DNA. We have extended this observations for bacteriophages G14 and U3. Restriction enzyme analysis placed the phi X gene A protein cleavage site in St-1 RF DNA in the HinfI restriction DNA fragment F10 and in the overlapping HaeIII restriction DNA fragment Z7. The exact position and the nucleotide sequence at the 3'-OH end of the nick were determined by DNA sequence analysis of the single stranded DNA subfragment of the nicked DNA fragment F10 obtained by gelelectrophoresis in denaturing conditions. A stretch of 85 nucleotides of St-1 DNA around the position of the phi X gene A protein cleavage site was established by DNA sequence analysis of the restriction DNA fragment Z7F1. Comparison of this nucleotide sequence with the previously determined nucleotide sequence around the cleavage site of phi X gene A protein in phi X174 RF DNA and G4 RF DNA revealed an identical sequence of only 10 nucleotides. The results suggest that the recognition sequence of the phi X174 gene A protein lies within these 10 nucleotides. PMID- 6253952 TI - Structure of a yeast non-initiating methionine-tRNA gene. AB - 4 to 8 kb Hind III fragments of yeast DNA were cloned into pBR322. One of these clones (pY6m3) containing a single tRNA3Met gene has been characterized in detail. The DNA sequence of the structural gene is colinear with the tRNA sequence, which means that in this case no intervening sequence is present. The 5'-leader and 3'-trailer sequences have also been determined. The 5'-flanking region can be folded up into possible secondary structures. PMID- 6253954 TI - Chemical synthesis of tridecanucleoside dodecaphosphate sequence of SV40 DNA. AB - The preparation, by the phosphotriester approach, of d[C-T-A-T-T-C-C-A-G-A-A-G-T] from one tetranucleoside triphosphate and three trinucleoside diphosphate blocks is described. The use of the o-dibromomethylbenzoyl (DBMB) protecting group in oligodeoxyribonucleotide synthesis is described for the first time. Internucleotide linkages are protected by o-chlorophenyl groups which are finally removed by treatment with the N1, N1, N3, N3-tetramethylguanidinium salt of syn-4 nitrobenzaldoxime. The first phosphorylation step (leading to phosphodiester intermediates) is carried out by treatment with o-chlorophenyl phosphorodi-(1,2,4 triazolide) followed by treatment with water and triethylamine. 1 Mesitylenesulphonyl-3-nitro-1,2,4-triazole (MSNT) is used as the activating agent in the second phosphorylation step in which 5'-protected mono- and di-nucleotides are condensed with nucleoside building blocks containing unprotected 3'-hydroxy functions. PMID- 6253956 TI - [Breast cancer coexistent with tumor of the uterine body and cervix]. PMID- 6253955 TI - [Effect of surgical procedures (diagnostic laparotomy with splenectomy) on body mass metabolism in Hodgkin's disease]. PMID- 6253957 TI - [Synergistic effect of inhalation of alleregen and polymyxin B in bronchial asthma]. PMID- 6253958 TI - [Polymyxin b inhalation test - a significant aid for establishing indications for intal therapy]. PMID- 6253959 TI - [1-24-ACTH stimulation test as a measure of effectiveness of bilateral adrenalectomy in Cushing's syndrome]. PMID- 6253960 TI - [Diagnosis of tumours in posterior cranial fossa by means of computerized tomography (author's transl)]. PMID- 6253961 TI - [The usefulness on angiography in the diagnosis of neoplasms of bones and soft tissues (author's transl)]. PMID- 6253962 TI - [Hepatitis A virus antibodies in preparations of normal immunoglobulin of Polish production]. PMID- 6253963 TI - [Hepatitis A and B virus antibodies among healthy Polish population]. PMID- 6253964 TI - [Opiate receptors and morphine-like endogenous peptides]. PMID- 6253965 TI - [Effect of adenosine cyclic-3',5'-monophosphate (cAMP) on thiamine hydrochloride passage through human erythrocyte membranes]. PMID- 6253966 TI - On the concept of carcinoma in situ of the breast. PMID- 6253967 TI - A hypothesis of the origin of human breast cancer from the terminal ductal lobular unit. PMID- 6253968 TI - Collagenase activity of cartilage in rats with experimental lathyrism: a model of bone diseases. AB - Collagenolytic activity was estimated in skin and joint cartilage of lathyritic rats by means of a biological assay. Lathyrism was induced by feeding beta aminopropionitrile fumarate for six weeks, and the lathyritic state was confirmed by characteristic radiographic, histomorphologic and biochemical findings. Both tissues in lathyritic animals revealed significantly increased collagenolytic activity in comparison with those of the control animals. Studies were performed using ethylendiaminetetraactate and normal rat serum to determine the origin of inhibition of the collagenolytic system inhibition. Since both agents showed no inhibition of collagenolysis, the highly increased collagenolytic activity in lathyritic skin and joint cartilage appears not to be derived from polymorphonuclear cells nor from serum, but from the tissue itself. Elevation of collagenase activity may be important with respect to the increased neutral salt solubility of collagen and hydroxyproline excretion observed in experimental lathyrism. PMID- 6253969 TI - Collagenolytic activity in hyperacute lung allograft rejection. AB - Six mongrel dogs were presensitized by full thickness skin grafts followed by orthotopic lung homotransplantation. Tissue explants of the hyperacutely rejected lung grafts were placed on the surface of a gel of native collagen. Collagenase activity was found in each specimen. Lungs of 10 untreated dogs served as controls. The collagenolytic system of the transplanted lungs was inhibited by EDTA only. No inhibitory effect was obtained by the inhibitor of bacterial collagenase, cysteine, and normal serum containing protease inhibitors. By means of inhibition studies it was tried to determine the origin of the collagenolytic activity. It is suggested that the enzyme effect is derived from the lysosomes of polymorphonuclear leukocytes. Collagenase of granulocytic origin seems to participate as mediator in the immunological reaction of hyperacute lung graft rejection. PMID- 6253970 TI - Malignant fibrous histiocytoma: histological patterns and cell types. PMID- 6253971 TI - Oat cell carcinoma of the stomach. AB - An autopsy case of oat cell carcinoma arising in the stomach is described. The histology of the tumor was similar to that of ordinary oat cell carcinoma of the lung, and the secretory granules were identified by electron microscopy. Except for the direct invasion of the perigastric region and metastasis of the liver, no tumor was found in the lungs or any other organs. The occurrence of this type of tumor in the stomach as in other extrapulmonary organs provides supplemental evidence for the existence of the carcinoid-oat cell carcinoma group, recently established in the lung. PMID- 6253972 TI - [Surgical sutures Dexon (author's transl)]. PMID- 6253974 TI - Diagnostic techniques in cardiovascular nuclear medicine. AB - "Hot-spot" and "cold-spot" myocardial imaging and first-pass and gated equilibrium blood pool studies are the most common cardiovascular nuclear medicine procedures. The data provided by these tests may be vitally important in making decisions, primarily in patients with suspected coronary artery disease. These studies are best performed where there is close coordination between the cardiovascular specialist and the nuclear medicine department. We believe that only a minority of patients with heart disease require these tests, but for those in whom they are indicated, the information obtained can be invaluable. PMID- 6253973 TI - Seroepidemiology of viral hepatitis: correlation with clinical findings. AB - Antibody to hepatitis A antigen (anti-HA) is detectable in the serum shortly after infection with hepatitis A virus. The presence of IgM antibody indicates acute infection; IgG signifies past infection. Hepatitis B surface antigen (HBsAg) indicates infectiousness and is usually present when hepatitis B virus causes active liver disease; its antibody (anti-HBs) is neutralizing and confers immunity. Antibody to core antigen (anti-HBc) is an index of hepatitis B viral replication when present in high titers; in low titers it reflects past infection. Early presence of e antigen (HBeAg) indicates a high degree of infectivity, whereas presence of its antibody (anti-HBe) indicates a lesser degree. Although markers of non-A non-B hepatitis have been described, the definitive nature and number of the virus or viruses are not yet clear. PMID- 6253975 TI - Clinical evaluation of pituitary adenomas. AB - Improvements in both diagnostic methods and surgical and medical treatment modalities for pituitary disease have been a major advance in endocrinology. Future refinements in visualization techniques and dynamic testing of pituitary function are to be expected and will further add to understanding of this complex spectrum of diseases. PMID- 6253976 TI - [Review of today's treatment of bronchial small cell anaplastic cancers (author's transl)]. AB - The median survival time of untreated patients with small cell anaplastic carcinoma of the lung does not exceed three months. An important improvement in survival and disease-free period has been achieved by some new therapeutic combinations including chemotherapy alone or radiotherapy and chemotherapy. These recent results are reviewed in this paper, and a new treatment schedule is presented. PMID- 6253977 TI - Constipation. PMID- 6253978 TI - Disorders affecting posture and gait. PMID- 6253979 TI - Haemorrhagic complications of anticoagulants. Heparin-induced femoral neuropathy. PMID- 6253980 TI - 'New' enteric infections. PMID- 6253981 TI - Infectious and exotic diseases in children. PMID- 6253982 TI - [Effect of cAMP on the growth and development of luminescence in Photobacterium belozerskii]. AB - The effect of cAMP on the parameters characterizing the development of luminescence in Photobacterium belozerskii is discussed. An addition of cAMP to the culture medium shortened the latent time of luminescence development by 3--6 hours. The intensity of bacterial luminescence increased with a varying rate. During luminescence enhancement the rate of luciferase synthesis increased by a factor of 10 to 10(3). The rate of luciferase synthesis and the maxiumum level of bacterial luminescence when cultivated in the glycerol medium containing arginine and proline increased under the influence of cAMP by 100 and 40 times, respectively. After an addition to cAMP into the glucose medium these parameters of luminescence development increased only when the medium contained arginine. After an addition of cAMP into the glycerol medium the rate of bacterial growth increased two-fold. Possible mechanisms regulating luminescence development and cAMP involvement in these processes are discussed. PMID- 6253983 TI - [Alpha-galactosidase producers among yeast cultures]. AB - The capacity for biosynthesis of alpha-galactosidase was examined in 89 yeast cultures belonging to 21 genera during submerged cultivation on a medium containing dry whey. This capacity was found only in one genus, namely Schwanniomyces. Optimal cultivation conditions were selected for the strain Schw. alluvius 1167 that showed the highest alpha-galactosidase activity. As a result, activity of alpha-galactosidase was increased 4.8 times as compared with the initial level. PMID- 6253984 TI - [Adrenal cortex glucocorticoid function in the early stages of the development of different forms of diabetes mellitus]. AB - An increase in the basal cortisol level in the blood plasma or the adrenal cortex reaction to insulin hypoglycemia was seen in patients in the early periods of diabetes mellitus (latent, initial manifest type). No considerable differences were found between the adrenals of juvenile and adult diabetic patients. Combined diabetes mellitus and obesity led to a significant rise in the indices studied. An intensification of the adrenocortical glucocorticoid function is not accompanied by an enhancement of the hypophysis adrenocorticotropic function. PMID- 6253985 TI - [Hormonal regulation of heparin clearance in immobilization stress in rats]. AB - Intensity of heparin (H) clearance is reduced and the latter gets retained in the blood flow in rats subjected to immobilization stress. A stable fall is seen when immobilization is continued not less than 20 minutes. A decrease in the rate of H secretion from the blood flow is associated with ACTH concentration in the blood. Immobilization stress does not affect the intensity of H clearance in the animals with ACTH-release blocked by DOCA administration. ACTH use was conducive to a further decrease in H clearance intensity in animals exposed to immobilization. The rate of H secretion from the blood flow in this case is minimum and significantly differs from the rate of H clearance in animals immobilized without ACTH administration. PMID- 6253986 TI - [Present-day concepts of the mechanism of the glucose induction of insulin secretion]. PMID- 6253987 TI - [Cytochemical indices as criteria of the activity of stage-I pulmonary sarcoidosis]. PMID- 6253988 TI - Predicted structure of two adenovirus tumor antigens. AB - Early adenovirus type 2(Ad2) mRNA sequences have been cloned by using the pBR322 plasmid as a vector. Two clones that include sequences from region E1B were identified and their DNAs were characterized by hybridization, restriction enzyme cleavage, and DNA sequence analysis. The results showed that the clones were derived from two different spliced mRNAs. By combining our results with the established DNA sequence for region E1B of the closely related adenovirus type 5[Maat, J., van Beveren, C.P. & van Ormondt, H. (1980) Gene, in press] it was possible to deduce the structure of a 13S and a 22S mRNA. The two mRNAs differ from each other by the size of their intervening sequences. If translation starts at the first AUG following the cap, the 22S mRNA encodes a Mr 67,000 polypeptide that is terminated by a UGA stop codon located immediately before the splice, whereas the 13S mRNA encodes a Mr 20,000 polypeptide that is translated in different reading frames before and after the splice. The Mr 20,000 and 67,000 polypeptides correspond in molecular weight to two proteins that invariably are precipitated from infected cell extracts by antisera from animals carrying adenovirus-induced tumors. PMID- 6253989 TI - The protein encoded by the transforming gene of avian sarcoma virus (pp60src) and a homologous protein in normal cells (pp60proto-src) are associated with the plasma membrane. AB - Oncogenesis by avian sarcoma virus is attributable to a single viral gene (src) which encodes a phosphoprotein (pp60src) with the enzymatic activity of a protein kinase. A closely related protein, pp60proto-src, occurs in uninfected cells from a wide variety of vertebrate species and is presumed to be the product of a cellular gene that served as progenitor for src. We explored the location of these proteins within the cell by using immunoprecipitation to analyze subcellular fractions prepared from avian sarcoma virus-transformed rat and chicken cells and from uninfected rat cells. We found that both pp60src and pp60proto-src were associated with the plasma membrane as active protein kinases and could be recovered efficiently only by disrupting the membranes with nonionic detergent. Our findings, in conjunction with those of other investigators, indicate that both proteins are embedded in the membrane by means of a hydrophobic domain(s); available evidence indicates that pp60src is not exposed on the surface of the cell but is accessible at the cytoplasmic aspect of the plasma membrane. These conclusions lend credence to two current speculations. First, pp60src and pp60proto-src may have similar or even identical functions. Second, neoplastic transformation may originate from derangements in the plasma membrane or its affiliated structures. PMID- 6253990 TI - Interaction between beta-adrenergic receptors and guanine nucleotide sites in turkey erythrocyte membranes. AB - beta 1-Adrenergic receptors from turkey erythrocyte membranes have been identified by specific binding of the radiolabeled antagonist (-) [3H]dihydroalprenolol. These receptors are inactivated by the alkylating agent N ethylmaleimide when occupied by beta-adrenergic agonists but not when occupied by antagonists or when unoccupied. A time-dependent decrease of the number of receptor sites is observed. Inactivation affects 45-60% of the sites, regardless of the agonist or N-ethylmaleimide concentration. The guanine nucleotides GTP and 5'-guanylyl imidodiphosphate effectively protect the receptors against agonist mediated inactivation by N-ethylmaleimide. Protection by ATP necessitates a 100 fold higher concentration; 10 mM NaF is ineffective. The guanine nucleotide effect is reversible and occurs via interaction with N-ethylmaleimide-insensitive sites. These observations establish that guanine nucleotide sites interact with and caused structural modification of the agonist-occupied beta-adrenergic receptors in turkey erythrocyte membranes. PMID- 6253992 TI - Calmodulin activates prokaryotic adenylate cyclase. AB - The adenylate cyclase of Bordetella pertussis is stimulated 100- to 1000-fold in a dose-dependent manner by calf brain calmodulin. The system has the following properties. (i) The activation is prevented by ethylene glycol bis(beta aminoethyl ether)-N,N,N',N'-tetraacetic acid and restored by Ca2+. (ii) Oxidation of the methionine residues of calmodulin abolishes the ability to activate the cyclase. (iii) Trifluoperazine inhibits calmodulin-activated cyclase. (iv) A troponin C preparation stimulates the B. pertussis cyclase with < 0.01 the potency of calmodulin. Although calmodulin has not been demonstrated in prokaryotes, this is an example of a (eukaryotic) calmodulin effect in a prokaryote. PMID- 6253991 TI - Comparative sequence analysis of the inverted terminal repetitions from different adenoviruses. AB - The comparative nucleotide sequences of the region of inverted terminal repetition from a representative member of group C (nononcogenic), group B (weakly oncogenic), and group A (highly oncogenic) adenoviruses are analyzed. Our data show that (i) the length of this unique region increases with the oncogenicity of the serotype, (ii) a unique homologous region--14 nucleotides long--is present exactly at the same distance from the terminus, and (iii) a hexanucleotide sequence, T-G-A-C-G-T, is present at the site where the terminal repetition diverges. PMID- 6253993 TI - Amplification of integrated viral DNA sequences in polyoma virus-transformed cells. AB - Polyoma virus (Py) transformation of rat cells requires integration of viral genomes into the host DNA, which generally occurs in a partial or full head-to tail tandem arrangement. The instability of this structure was previously demonstrated by the high rate of loss of integrated Py genomes in the presence of viral large tumor (T) antigen. We now show that integrated Py DNA sequences can also undergo amplification. We studied two rat cell lines transformed by the ts-a Py mutant, which codes for a thermolabile large T antigen. In a derivative of the ts-a H6A cell line, we have observed loss of full-length Py DNA molecules from the integrated tandem ("curing"), accompanied by the creation of new tandem repeats of two segments of viral DNA corresponding to 38% and 10% of the viral genome, each containing the origin of DNA replication. In the ts-a H3A cell line, which contains an integrated partial tandem of about 1.3 viral genomes with three distinct deletions, propagation at 33 degrees C resulted in the generation of full tandem repeats of a 94% Py DNA "unit" (including two 3% deletions), an 85% "unit" (including a 3% and the 12% deletion), or both. Amplification of integrated viral DNA was not observed in cells propagated at 39.5 degrees C, the nonpermissive temperature for large T antigen function. Amplification of integrated Py DNA sequences thus requires an active large T antigen and can generate a full tandem of integrated viral DNA molecules long after the initial integration event. PMID- 6253994 TI - Cloning and mapping of BamHi endonuclease fragments of DNA from the transforming B95-8 strain of Epstein-Barr virus. AB - DNA from the B95-8 strain of Epstein-Barr virus was cleaved into 29 different fragments by BamHI endonuclease (EC 3.1.23.6). All of the fragments except the terminal fragments have been inserted into the pBR322 cloning vector and replicated in Escherichia coli. The location of each cloned DNA fragment in the viral genome has been determined, providing a more detailed physical map of the genome than has been available previously. PMID- 6253995 TI - Deletions covering the putative promoter region of early mRNAs of simian virus 40 do not abolish T-antigen expression. AB - A recombinant plasmid was constructed by insertion of the early genes of simian virus 40 (SV40) into pBR322. When it was introduced into eukaryotic cells, the SV40 early genes were expressed. We have made deletion mutants of this plasmid, from which the major cap sites of SV40 early mRNAs have been removed along with some of the sequences upstream. The deleted sequences appear to be dispensable for early gene expression, but this does not necessarily imply that they serve no function in the initiation of transcription on wild-type SV40. PMID- 6253996 TI - Transport of vesicular stomatitis virus glycoprotein in a cell-free extract. AB - We describe a cell-free system in which the membrane glycoprotein of vesicular stomatitis virus is rapidly and efficiently transported to membranes of the Golgi complex by a process resembling intracellular protein transport. Transport in vitro is energy-dependent and is accompanied by terminal glycosylation of the membrane glycoprotein (dependent upon UDP-GlcNAc and resulting in resistance to endo-beta-N-acetylglucosaminidase H). PMID- 6253997 TI - Involvement of cyclic GMP in intracellular signaling in the chemotactic response of Escherichia coli. AB - The intracellular signal that produces changes in swimming behavior when bacteria encounter attractants or repellents has not previously been identified. We suggest, based on the following lines of evidence, that cyclic GMP (cGMP) is involved in this signaling process in chemotaxis by Escherichia coli. (i) The addition of attractants to bacteria causes a transient increase in the intracellular level of cGMP, whereas a repellent stimulus decreases the level transiently. These changes do not generally occur in a mutant lacking chemotaxis specific proteins. (ii) In the absence of chemoeffectors, both addition of cGMP to bacteria and reducing the intracellular cGMP level produce changes in swimming behavior, and a mutant with an abnormal swimming pattern has an altered intracellular cGMP level. (iii) cGMP modulates the demethylation reaction responsible for adaptation to stimuli. (iv) Mutants defective in components of the adaptation system have altered cGMP metabolism. PMID- 6253998 TI - Vesicular stomatitis virus glycoprotein is anchored in the viral membrane by a hydrophobic domain near the COOH terminus. AB - We have determined the COOH-terminal and NH(2)-terminal amino acid sequences of the vesicular stomatitis virus (VSV) glycoprotein (G). A sequence of 122 COOH terminal amino acids was deduced from the complete sequence of a cloned DNA insert carrying 470 nucleotides derived from the 3' end of the G mRNA. Evidence presented indicates that this portion of the polypeptide includes the domains of G that reside inside the virion and span the lipid bilayer of the virion. This seems clear because a partial amino acid sequence of a fragment of G that remains associated with the membrane of the virion after exhaustive proteolytic digestions can be located unambiguously in the predicted sequence. This predicted sequence contains an uninterrupted hydrophobic domain beginning 49 amino acids and ending 30 amino acids from the COOH terminus. This region presumably spans the lipid bilayer. The COOH-terminal portion of 29 amino acids contains a high proportion of basic residues and resides inside the virion. The COOH-terminal portion of the VSV G protein therefore resembles in structure that of glycophorin, an erythrocyte membrane protein well characterized previously. The configuration of G in the viral membrane demonstrated here is probably similar for other viral glycoproteins, although this has not been tested as directly in any other case. From the sequence of a DNA primer extended on the RNA genome from the adjacent M protein gene into the G protein gene, we have deduced an NH(2) terminal G protein sequence of 53 amino acids, including the leader sequence of 16 amino acids. Our sequence confirms, extends, and corrects two partial amino acid sequences reported for this region previously. PMID- 6253999 TI - Evidence for formation of a rabbit liver aldolase--rabbit liver fructose-1,6 bisphosphatase complex. AB - The ability of rabbit liver aldolase (D-fructose-1,6-bisphosphate D glyceraldehyde-3-phosphatate-lyase, EC 4.1.2.13) and rabbit liver fructose-1,6 bisphosphatase (Fru-P2ase; D-fructose-1,6-bisphosphate 1-phosphohydrolase, EC 3.1.3.11) to partition into the gel phase of Ultrogel AcA 34 is decreased in a mixture of the two enzymes. Titration experiments indicate that a 1:1 complex is formed. The value for the distribution coefficient of the complex corresponds to a molecular mass of 300,000 daltons, the value expected for a dimer containing one mole of each enzyme protein. Complex formation was not observed when either liver enzyme was replaced by the corresponding isozyme from rabbit muscle. The susceptibility of liver Fru-P2ase to limited proteolysis by subtilisin was reduced in the presence of liver aldolase, but not when the latter was replaced by muscle aldolase, suggesting that the conformation of Fru-P2ase is altered in the complex. Limited proteolysis of liver aldolase abolishes its ability both to form the heterodimer and to protect Fru-P2ase from modification by subtilisin. PMID- 6254000 TI - Expression of early genes of origin-defective mutants of simian virus 40. AB - The nucleotide sequences of eight origin-defective mutants of simian virus 40 have been determined. All of the mutants have suffered deletions, which range in size from 4 to 241 nucleotides. Some of the mutants induce the synthesis of tumor (T) antigen, others do not. Viral mRNA extracted from rat cells transformed by two of the T-antigen-positive mutants has been analyzed by the S1 nuclease technique of Berk and Sharp. Irrespective of the size or the location of the deletions, the 5' ends of viral mRNAs are located approximately the same distance from the A+T-rich region (A-T-T-T-A-T) rather than at a specific site in the viral genome. PMID- 6254001 TI - Nucleotide sequence of the primary origin of bacteriophage T7 DNA replication: relationship to adjacent genes and regulatory elements. AB - The 682-base-pair nucleotide sequence between positions 14.45 and 16.15 on the bacteriophage T7 DNA molecule has been determined. We can identify not only the sequence of the primary origin of DNA replication but also the termination of gene 1, all of genes 1.1 and 1.2, the start of gene 1.3, and a number of regulatory sequences. The endpoints of four deletion mutations that extend into this region have been determined. These mutations are inferred to have arisen by recombination between short homologous sequences, three of which ar T7 RNA polymerase promoters. The base changes of four point mutations in gene 1.2 have been identified. The sequence essential for initiation at the primary origin is located between the left endpoints of the two deletions D2 and D303. Sequence analysis of these mutants assigns the primary origin to a 129-base-pair segment between positions 14.73 and 15.05. This intergenic segment is A+T-rich (75%) and contains a single T7 gene 4 protein recognition site; it is preceded by two tandem T7 RNA polymerase promoters. A model for initiation of T7 DNA replication is presented. PMID- 6254002 TI - Synthesis in vitro of the full-length complement of defective-interfering particle RNA of vesicular stomatitis virus. AB - Under appropriate reaction conditions in vitro, four different defective interfering particles of vesicular stomatitis virus have been shown to synthesize the full-length complement of their RNAs. The reaction involved preinitiation of the core particles with ATP and CTP, followed by RNA chain elongation in the presence of the beta, gamma-imido analogue of ATP, AdoPP[NH]P, and the three normal ribonucleoside triphosphates. By hybridization of the in vitro synthesized plus strand with the standard genome RNA followed by RNase treatment of the heteroduplexes, we have shown that the RNA of a defective-interfering particle derived from the 3' end of the genome RNA has evolved by an internal deletion of the standard genome. PMID- 6254003 TI - Nucleotide sequences of integrated Moloney sarcoma provirus long terminal repeats and their host and viral junctions. AB - Integrated Moloney murine sarcoma provirus (MSV) has direct terminal repeat sequences (TRS). We determined the nucleotide sequence of both 588-base-pair TRS elements and the adjacent host and viral junctions of an integrated MSV cloned in bacteriophage lambda. Sequences were identified corresponding to the tRNAPro primer binding site in genomic RNA and the reverse-transcribed minus strong stop DNA. Each 588-base-pair repeat contains putative sites for promoting RNA synthesis and RNA polyadenylylation. The first and last 11 nucleotides of the TRS are inverted with respect to each other, and the same four-nucleotide host sequence is found bracketing integrated MSV. Some similarities of TRS and prokaryotic insertion sequence elements are discussed. PMID- 6254004 TI - Isolation, structure, biological characterization, and synthesis of beta [Tyr9]melanotropin-(9-18) decapeptide from pig hypothalami. AB - A decapeptide with the amino acid sequence H-Tyr-Phe-Arg-Trp-Gly-Ser-Pro-Pro-Lys Asp-OH was isolated from acid extracts of porcine hypothalami, structurally and biologically characterized, and synthesized. Except for the NH2-terminal tyrosine, this decapeptide corresponds to the amino acid sequences 9-18 of porcine beta-melanotropin (beta-MSH) and 49-58 of porcine beta-lipotropin (beta LPH); it also has a tetrapeptide sequence of amino acids (Phe-Arg-Trp-Gly) common to the 7-10 sequences in corticotropin (ACTH) and alpha-MSH. beta-MSH, beta-LPH, alphaMSH, and ACTH from various species all have a histidine residue in the position immediately preceding the common sequence, and the occurrence of a natural peptide with the tyrosine residue in the corresponding site has not been previously reported. This suggests that the beta-[Tyr9]MSH-(9-18) decapeptide might be a fragment of a still larger precursor (prohormone) possibly related to beta-LPH. PMID- 6254005 TI - Photoaffinity labeling of corticotropin receptors. AB - A photoaffinity label for corticotropin (ACTH) receptors was prepared by selective chemical modification of the single tryptophan residue in the hormone by reaction with 2-nitro-5-azidophenylsulfenyl chloride. The photoreactive derivative, [(2-nitro-5-azidophenylsulfenyl)-Trp9]ACTH (2,5-NAPS-ACTH), stimulated corticosterone synthesis to 60% of the maximal rate induced by ACTH in isolated rat adrenocortical cells. 2.5-NAPS-ACTH caused only a marginal stimulation of cyclic AMP production compared to the unmodified hormone. Stimulation of corticosterone production and cyclic AMP accumulation induced by ACTH were both inhibited in a competitive manner by 2,5-NAPS-ACTH. Photolysis of adrenocortical cells in the presence of 2,5-NAPS-ACTH resulted in a 40% inactivation of ACTH receptors mediating steroidogenesis, as shown by the decrease in response to subsequent stimulation with ACTH. No loss of function was observed when photolysis was conducted in the presence of the photoresistant analog [(2,4-dinitrophenylsulfenyl)-Trp9]ACTH. Covalent attachment of the hormone to the receptors was also demonstrated by photolyzing adrenocortical cells in the presence of tritiated 2,5-NAPS-ACTH of high specific radioactivity (90 Ci/mmol) and analyzing the cell proteins by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. A protein with an approximate molecular weight of 100,000 was specifically labeled by this procedure. The unique labeling of an adrenocortical cell protein and the concomitant loss of ACTH responsiveness suggest that physiologically relevant receptors are photolabeled by this method. PMID- 6254006 TI - Transformation of rat embryo fibroblasts by cloned polyoma virus DNA fragments containing only part of the early region. AB - Recombinant plasmids containing either the entire polyoma viral genome or one or the other of the two HindIII fragments of polyoma virus DNA were constructed and cloned in Escherichia coli X1776, and their DNAs were individually tested for the capacity to transform an established line of rat cells. The recombinant plasmids containing the entire polyoma genome and those containing the HindIII-1 fragment of polyoma DNA (45-1.4 map units) efficiently transform rat cells, whereas the plasmids containing the HindIII-2 fragment (1.4-45.0 map units) do not. The properties of many independent transformed cell lines established by infection with the cloned HindIII-1 fragment were determined. In contrast to the parent cell line, rat cells transformed with the cloned HindIII-1 fragment grow to high saturation densities, form colonies with high efficiency in dilute agar suspension, produce high levels of plasminogen activator, and display a disorganized arrangement of actin cables. By all criteria examined, these cells transformed by fragments are indistinguishable from cells transformed by whole polyoma viral DNA. Cellular DNA prepared from many HindIII-1 fragment-transformed cell lines was analyzed for the presence and arrangement of polyoma viral sequences by Southern blot-hybridization. In all cases examined, only those viral sequences contained within the HindIII-1 fragment of polyoma DNA were detected. These data establish a strong correlation between polyoma DNA sequences mapping within a restricted portion of the early region and the induction and maintenance of the transformed phenotype. PMID- 6254007 TI - Cytoplasmically made subunits of yeast mitochondrial F1-ATPase and cytochrome c oxidase are synthesized as individual precursors, not as polyproteins. AB - At least three subunits of yeast mitochondrial F1-ATPase (ATP phosphohydrolase, EC 3.6.1.3) and at least two subunits of cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1) are synthesized outside the mitochondria and imported into the organelles as individual precursors that are between 2000 and 6000 daltons larger than the mature subunits. These precursors were shown to be primary translation products. Therefore, neither the five F1 subunits nor the four small cytochrome c oxidase subunits are synthesized as a single polyprotein. PMID- 6254008 TI - Nucleotide sequence of the bacterial transposon Tn1681 encoding a heat-stable (ST) toxin and its identification in enterotoxigenic Escherichia coli strains. AB - the Escherichia coli heat-stable toxin (ST I) is encoded within a transposon (Tn1681) flanked by inverted repeats of insertion sequence 1 (IS1) [So, M., Heffron, F. & McCarthy, B. J. (1979) Nature (London) 277, 453-456]. By subcloning restriction fragments and by insertion mutagenesis, we located precisely the gene for ST I within the transposon. We determined the complete nucleotide sequence of the central portion of Tn1681 (i.e., that part flanked by IS1) and identified the coding sequence of the toxin. From the nucleotide sequence, we deduced a probable amino acid sequence for ST I. The NH2-terminal portion of the amino acid sequence is extremely hydrophobic and bears a striking resemblance to the signal sequence of the fd phage minor coat protein. By using a subcloned restriction fragment containing the gene for ST I but no IS1 sequences, we determined (i) that the ST toxin with activity assayable in suckling mice (ST I) is genetically distinct from the St toxin assayable in ligated ileal loops (ST II) and (ii) that ST I can be responsible for diarrheal disease in different animals. PMID- 6254010 TI - Induction and properties of beta-adrenergic receptors during erythroid differentiation of Friend leukemic cells. AB - beta-Adrenergic receptors on Friend erythroleukemic cells were identified by the use of 125I-labeled hydroxybenzylpindolol, a potent beta-adrenergic antagonist. Binding of this ligand was saturable and stereospecific. The relative orders of potency of isoproterenol, epinephrine, and norepinephrine to displace bound hydroxybenzylpindolol indicate that the Friend cells have beta 2-adrenergic receptors. After culture for 6 days in the presence of dimethyl sulfoxide or hexamethylene bisacetamide, both undifferentiated and differentiated cells have a similar number of receptors (1500 per cell), but the density of beta receptors on the cell surface increases during the process of erythroid differentiation. Incubation of the Friend cells for 24 hr with high concentrations of butyric acid, dimethyl sulfoxide, or hexamethylenebisacetamide resulted in a striking increase of th number of beta-catecholamine receptors. The induction of beta adrenergic receptors also occurred in the presence of the tumor promoter 12-O tetradecanoylphorbol 13-acetate and dexamethasone. PMID- 6254009 TI - Activation of electrogenic Na+/K+ exchange by extracellular K+ in canine cardiac Purkinje fibers. AB - Transient increments in sodium pump current were elicited in small voltage clamped Purkinje fibers suspended in a fast flow system by briefly exposing them to K+-free fluid, to temporarily inhibit the pump, and then suddenly returning them to K+-containing fluid. The exponential time course of decay of the current increment provides a measure of the pump rate constant for Na+ extrusion. The dependence of that rate constant, and of the peak amplitude of the increment in pump current, on the extracellular K+ concentration was determined. The results indicate: that in cardiac Purkinje cells, as in many other cells, the pump is half-maximally activated by about 1 mM K+; that the coupling ratio for Na+/K+ exchange is independent of either intracellular Na+ concentration or external K+ concentration; and that a simple model in which intracellular Na+ concentration is determined by a passive "leak," and an active extrusion of Na+, seems sufficient to account for moderate changes in cellular Na+ concentration. PMID- 6254011 TI - Uniparental propagation of mitochondrial DNA in mouse-human cell hybrids. AB - The retention of the two parental mitochondrial DNAs has been investigated in a large number of mouse-human cell hybrids segregating either mouse or human chromosomes, by using a highly sensitive and specific method for detection of the DNA; the results have been correlated with the karyotype and isozyme marker pattern in the same hybrid lines. In all the hybrids examined, a consistent pattern was observed for the type of mitochondrial DNA retained: the mitochondrial DNA of the parent whose chromosomes were segregated from the nucleus was undetectable or present in marginal amounts. This was true also of hybrids containing a complete set of the segregating chromosomes in the total or a large fraction of the cell population. PMID- 6254012 TI - Differences in intracellular location of pp60src in rat and chicken cells transformed by Rous sarcoma virus. AB - We have investigated the intracellular location of pp60src in Rous sarcoma virus transformed rat cells (RR1022) by indirect immunofluorescence microscopy and cell fractionation. Immunofluorescence data suggest that pp60src is predominantly associated with the nuclear envelope and the juxtanuclear reticular membrane structures. The bulk of pp60src and of the associated phosphotransferase activity fractionated with nuclei and not with plasma membranes in disrupted cells. This localization contrasts strikingly with the association of pp60src with the plasma membrane of Rous sarcoma virus-transformed chicken fibroblasts. We propose that pp60src is a membrane protein that associates with cellular membranes through hydrophobic regions and that this membrane association is a general feature of the interaction of pp60src with avian and mammalian cells. Although there are major differences in the intracellular localizations of pp60src, it may interact with cellular membranes through one or more NH2-terminal hydrophobic regions. PMID- 6254013 TI - The four cytoplasmically made subunits of yeast mitochondrial cytochrome c oxidase are synthesized individually and not as a polyprotein. AB - Subunit-specific antisera prepared against each of the four cytoplasmically made subunits (IV, V, VI, and VII) of yeast mitochondrial cytochrome c oxidase (EC 1.9.3.1) were used to precipitate immunoreactive polypeptides that were synthesized either in vitro, in a cell-free protein-synthesizing system programmed with total yeast mRNA, or in vivo, in intact cells and in spheroplasts, under conditions of pulse labeling, pulse-chase labeling, and continuous labeling. Using N-formyl-[35S]Met-rTNA as the only radioactively labeled component in the cell-free system, we demonstrated (i) that each of the four cytoplasmically made subunits is synthesized as a separate entity and not as part of a polyprotein as was claimed by others; (ii) that subunits IV, V, and VI are synthesized as precursors, larger by 1500-3000 daltons than their mature counterparts; in contrast, subunit VII is not synthesized as a larger precursor. Precursor forms of subunits IV, V, and VI identical to those synthesized in vitro were also detected in vivo by pulse-labeling of spheroplasts. The observed disappearance of these larger forms after a chase is compatible with the notion that they represent short-lived precursors that are rapidly converted to their mature counterparts during or shortly after import into mitochondria. Furthermore, using N-formyl-[35S]Met-tRNA, we provide definitive evidence that two of the cytoplasmically made subunits (beta and gamma) of another oligomeric inner mitochondrial membrane protein (F1-ATPase, EC 3.6.1.3) are not synthesized as part of a polyprotein but as individual precursors. PMID- 6254014 TI - Genetic analysis of epidermal growth factor action: assignment of human epidermal growth factor receptor gene to chromosome 7. AB - Purified murine epidermal growth factor (EGF) binds to mouse and human cells. Two mouse transformed cell lines of different origins, PG19 and B82, were found to lack EGF receptors (EGFR). The defect in each of these two cell lines seems to be identical because they fail to complement each other. Somatic cell hybrids between these EGFR-deficient mouse cells and human cells expressing EGFR were produced. Several of these hybrids bound labeled EGF. Detailed cytogenetic analysis of these cell hybrids, followed by correlation of EGFR expression with human chromosomes revealed that EGFR presence correlated with human chromosome 7. The results suggest that the structural gene or a gene necessary for expression of the human EGF receptor is located on human chromosome 7. PMID- 6254015 TI - Cloning of reiterated and nonreiterated herpes simplex virus 1 sequences as BamHI fragments. AB - Over 95% of the herpes simplex virus type 1 (strain F) DNA sequences have been cloned as BamHI fragments in the pBR322 plasmid. With one exception, all of the cloned fragments have the same electrophoretic mobilities and restriction enzyme cleavage sites as do the authentic fragments derived from the BamHI digests of the viral genome. The exception is the BamHI B fragment mapping at the right end of L component in the prototype arrangement of the DNA. Thus, a small deletion mapping near the left end of the fragment was present in two independently derived plasmids. Included in the collection of plasmids are several clones containing DNA sequences that span the junction between the L and S components of the virus DNA. Several plasmids containing the junction fragment were found to be sufficiently stable to permit the preparation of large amounts of the DNA fragment for fine-structure mapping of the restriction enzyme cleavage sites. Preliminary studies on one cloned fragment (BamHI G) have shown that it is biologically active in marker rescue of a temperature-sensitive mutation and in transfer of a plaque morphology marker. PMID- 6254017 TI - HLA antigen-related restriction of T lymphocyte cytotoxicity to Epstein-Barr virus. AB - The specificity of cytotoxic T cells generated in Epstein-Barr virus (EBV) infected lymphocyte cultures was investigated, using a 51Cr release assay. Potent cytotoxic T cells with preferred specificity directed to antigens expressed on autologous lymphoblastoid cell line (LCL) target cells were present in 14-day cultures of lymphocytes from EBV-seropositive donors and not from seronegative donors. Moreover, the cytotoxic patterns obtained with a panel of HLA antigen related and unrelated LCL target cells, supported by unlabeled target inhibition tests, strongly indicate that T cell cytotoxicity to EBV is restricted to HLA antigens. PMID- 6254016 TI - Cloning and characterization of DNA sequences surrounding the human gamma-, delta , and beta-globin genes. AB - The human gamma-, delta-, and beta-globin genes are located within a 30-kilobase (kb) region of DNA, of which only 20% represents the globin genes. We have attempted to define the nature of flanking and intergenic sequences by isolating recombinants containing the human epsilon, both gamma-, or the 3' end of the beta globin gene from a bacteriophage library of cloned human DNA. Comparison of these recombinants and a recombinant containing the delta- and beta-globin genes (H beta G1) has provided the following results. The epsilon-globin gene is located 14 kb 5' to the G gamma gene. DNA sequence homology between the region containing the two G gamma genes and the delta nd beta gene region is limited to only a few hundred nucleotides which include the globin coding sequences. Repetitive DNA sequences have been found in the region 3' to the beta-globin gene. Sequences located adjacent to the beta-globin gene are repeated in the globin gene region. A repetitive DNA sequence more than 3.2 kb long is repeated frequently in the human genome but is not repeated in the globin gene region in the clones examined. PMID- 6254018 TI - Abnormal net Na+ and K+ fluxes in erythrocytes of three varieties of genetically hypertensive rats. AB - Net Na+ and K+ fluxes were measured in Na+-loaded and K+-depleted erythrocytes of three varieties of genetically hypertensive rats. In Okamoto spontaneously hypertensive rats (4 and 10-12 weeks of age), Na+ extrusion was reduced as compared to normotensive controls (Wistar/Kyoto). Na+ extrusion was also reduced in the hypertension-prone substrain of the Hebrew University Sabra rats as compared to the Na+-resistant substrain. K+ fluxes were similar in both groups. In both Okamoto spontaneously hypertensive rats and the hypertension-prone substrain, hypertension was severe and developed rapidly. In the Lyon spontaneously hypertensive rats, in which the blood pressure elevation is less severe than in other genetically hypertensive rats, erythrocyte net Na+ extrusion was the same as in normotensive controls, but net K+ gain was slightly increased. These erythrocyte abnormalities, observed in three varieties of genetically transmitted hypertension of the rat, are in several aspects similar to those previously described in accelerated and benign human essential hypertension. Erythrocyte Na+ and K+ net flux alterations may thus represent biochemical markers of primary hypertension. PMID- 6254019 TI - Resistance of an adenosine kinase-deficient human lymphoblastoid cell line to effects of deoxyadenosine on growth, S-adenosylhomocysteine hydrolase inactivation, and dATP accumulation. AB - Accumulation of dATP derived from 2'-deoxyadenosine (dAdo), causing inhibition of ribonucleotide reductase and depletion of the other deoxynucleotide substrates required for DNA synthesis, has been suggested as the cause of the lymphopenia and immune defect in inheritable deficiency of adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4). dAdo also inactivates the enzyme S adenosylhomocysteine hydrolase (AdoHcyase; S-adenosyl-L-homocystein hydrolase EC 3.3.1.1) which is involved in the catabolism of S-adenosyl-L-homocysteine (AdoHcy), both a product and a potent inhibitor of S-adenosylmethionine-dependent transmethylation. We have tried to determine whether inactivation of AdoHcyase might also contribute to dAdo toxicity to adenosine deaminase-inhibited cells. dAdo rapidly inactivates intracellular AdoHcyase and causes the accumulation of AdoHcy in WI-L2 human B lymphoblastoid cells. Low concentrations of adenosine (Ado), which block binding of dAdo to purified AdoHcyase, prevented inactivation of intracellular AdoHcyase and also lessened the growth-inhibitory effect of dAdo. A mutant of this cell line which lacks Ado kinase and accumulated endogenously synthesized Ado was resistant to the effects of dAdo on both growth and AdoHcyase activity. The mutant also accumulated far less dATP from dAdo than did its parent and was resistant to the inhibitory effect of dAdo on DNA synthesis, indicating the Ado kinase is involved in dAdo phosphorylation in these cells. Combinations of deoxycytidine, thymidine, and deoxyguanosine that could prevent dATP-mediated depletion of deoxynucleotide pools but not AdoHcyase inactivation were less effective than Ado in preventing dAdo toxicity to normal lymphoblasts. Our results suggest that inactivation of AdoHcyase, as well as dATP accumulation, contributes to dAdo toxicity. PMID- 6254020 TI - Tyrosine administration increases striatal dopamine release in rats with partial nigrostriatal lesions. AB - Partial, unilateral nigrostriatal lesions of varying severity were produced in rats by injecting graded doses of 6-hydroxydopamine into the substantia nigra. Formation of the dopamine metabolites dihydroxyphenylacetic acid and homovanillic acid in each surviving nigrostriatal neuron (estimated by the ratios of dihydroxyphenylacetic acid to dopamine and homovanillic acid to dopamine in the striatum) increased significantly when dopamine concentrations in striata containing lesions had been reduced to 25% or less of control values, but remained unchanged in rats with less severe lesions. These findings suggest that, in rats with severe damage of nigrostriatal dopaminergic neurons, surviving neurons increase their firing rates and accelerate dopamine synthesis and release. In rats that had lesions and enhanced striatal dopamine release, but not in rats with lesser lesions (i.e., which reduced ipsilateral dopamine concentrations by less than 75%), administration of tyrosine (250 mg/kg) caused further significant increases in formation of dihydroxyphenylacetic acid and homovanillic acid. These findings provide further evidence that tyrosine availability can enhance dopamine synthesis in and release from nigrostriatal neurons if the firing rates of these neurons are accelerated. PMID- 6254021 TI - Hormone-receptor interactions are noncooperative: application to the beta adrenergic receptor. AB - We have developed kinetic methods with which we have demonstrated that the negatively cooperative hormone-binding model is untenable for the insulin receptor system. These methods have led others to the same conclusion for the thyrotropin and nerve growth factor receptors. We report here the application of these methods to the study of (l)-[propyl-2,3-3H]dihydroalprenolol [(l)-[3H]DHA] binding at 15 degrees C to the beta-adrenergic receptor of the frog erythrocyte- the remaining and most extensively characterized hormone receptor-cyclase system in which negatively cooperative site-site interactions have been reported. Scatchard analysis of the equilibrium binding data for (l)-[3H]DHA in this system is linear. In addition, increasing concentrations of (l)-[3H]DHA during the binding reactions resulted in increasing receptor occupancy but no enhancement of the subsequent dilution-induced dissociation of bound hormone, demonstrating directly that the dissociation rate is independent of occupancy. Furthermore, analysis of the time course of the approach-to-equilibrium for this system at different hormone concentrations was consistent with reversible hormone binding to a homogeneous class of noncooperative receptors, and the analysis yielded a kinetically estimated equilibrium constant consistent with that derived from the linear equilibrium data. The above data indicate that negatively cooperative site site interactions are not a significant factor for the beta-adrenergic receptor of the frog erythrocyte. These results complete the demonstration that for all known hormone receptor systems, the hormone binds noncooperatively to one or more classes of independent receptor sites. The need for critical reinterpretation of detailed thermodynamic, clinical, and hormone analogue studies based on the negative cooperativity model is discussed. PMID- 6254022 TI - Most sequence differences between the genomes of the Akv virus and a leukemogenic Gross A virus passaged in vitro are located near the 3' terminus. AB - The 70S genomic RNA of nonleukemogenic AKR(Akv) virus was compared to that of an in vitro passaged, cloned, leukemogenic Gross A virus by fingerprint and sequence analysis. Fifty-seven of the large ribonuclease T1-resistant oligonucleotides of each virus have the same electrophoretic mobility and sequence. Thirteen large ribonuclease T1 oligo nucleotides are unique to the Gross A virus, whereas five are unique to Akv. Four of the oligonucleotides unique to each virus are related by one or two simple base changes. Five of the differences in oligonucleotides are located in the region of the genome that codes for the gag and pol genes. Eight of the differences are located near the 3' poly(A) terminus of the virus. The origins and biological consequences of these differences are discussed. PMID- 6254023 TI - Separation of random fragments of DNA according to properties of their sequences. AB - The separation of DNA fragments by electrophoresis at high temperature in a denaturing gradient is independent of the length of the fragments. We have suggested that the basis of fragment separation is that each DNA molecule undergoes partial melting as it encounters a concentration of denaturants sufficient to melt its least stable sequence, while other sequences remain double stranded; in the partially melted configuration, DNA can continue migration only slowly. This model is consistent with the observation that fragments of lambda phage DNA cleaved by different restriction endonucleases reach the same final depth in the gel if they contain the same least-stable sequence. A unique set of bands is produced from the electrophoresis of randomly fragmented DNA; this would be expected if there were a limited number of melting centers occupying discrete genetic loci. An intact DNA molecule penetrates about as deeply into the gel as the uppermost band after fragmentation; this would be expected only if the least stable sequence controls the final depth of the whole molecule. PMID- 6254024 TI - Mapping of anion binding sites on cytochrome c by differential chemical modification of lysine residues. AB - The carbonate binding site on horse cytochrome c was mapped by comparing the yields of carboxydinitrophenyl-cytochromes c, each with a single carboxydinitrophenyl-substituted lysine residue per molecule, when the modification reaction was carried out in the presence and absence of carbonate. The site is located on the "left surface" of the protein and consists of lysine residues 72 and/or 73 as well as 86 and/or 87 (Carbonate Site). Although one of the binding sites for phosphate on cytochrome c (Phosphat Site I) is located near the carbonate site, the sites are distinctly different since carbonate does not displace bound phosphate, as monitored by 31P NMR. Furthermore, citrate interacts with Phosphate Site I with high affinity, whereas chloride, acetate, borate, and cacodylate have a much lower affinity for this site, if they bind to it at all. The affinity of phosphate for Phosphate Site I (KD = 2 X 10(-4) M) is at least 1 order of magnitude higher than it is for other sites of interaction. PMID- 6254025 TI - Photoaffinity label for the beta-adrenergic receptor: synthesis and effects on isoproterenol-stimulated adenylate cyclase. AB - An azide derivative of the beta-adrenergic antagonist acebutolol has been synthesized and its effect examined on the isoproterenol-stimulated adenylate cyclase [ATP pyrophosphate-lyase (cyclizing); EC 4.6.1.1] activity of rat reticulocytes. It behaved as an effective competitive antagonist (Kd = 2 X 10(-7) M) prior to photolysis. However, when the reticulocyte preparation pretreated with acebutolol azide was photolyzed, a noncompetitive inhibition of isoproterenol-stimulated adenylate cyclase was obtained. Photolysis of the azide derivative in buffer alone did not convert it to a product of higher affnity. Labeling of the beta-adrenergic receptor appeared to be irreversible; multiple washings could not reverse the inhibition produced during photolysis with the label whereas washing would completely reverse the antagonism produced by the same concentration of label prior to photolysis. The effect appears to be specific for the beta-adrenergic receptor because the inhibition could be blocked stereoselectively by propranolol and there was no inhibition of fluoride- or GMP P(NH)P-stimulated adenylate cyclase. furthermore, no effect was observed on the glucagon-mediated stimulation of adenylate cyclase of liver membranes, whereas the catecholamine response in the same membranes was inhibited. PMID- 6254026 TI - Genomic changes associated with antigenic variation of visna virus durig persistent infection. AB - Visna virus undergoes antigenic change during persistent infection of sheep. Antigenic variants of visna virus were compared by using the genomic RNA and analyzing the large RNase T1-resistant oligonucleotides. Mutants isolated from a persistently infected sheep contained a small number of changes in their oligonucleotide patterns when compared with parental virus. To determine whether the changes in the nucleotide structure were clustered in one region of the genome, we determined the order of the oligonucleotides of the parental and mutant RNAs along the genome with respect to the 3' polyadenylylated end. All but one difference between the parental strain and the antigenic mutant used for mapping were located within 2 kilobases from the 3' terminus. Nucleotide sequence analyses showed that several of the oligonucleotides that differed in the parental and mutant RNAs could be accounted for by single base changes. PMID- 6254027 TI - Direct inhibition of testicular function by gonadotropin-releasing hormone: mediation by specific gonadotropin-releasing hormone receptors in interstitial cells. AB - Agonist analogs of gonadotropin-releasing hormone (GnRH) have been shown to exert antigonadal effects in male and female animals. In hypophysectomized male rats treated with follicle-stimulating hormone, administration of a potent GnRH agonist caused depletion of luteinizing hormone and prolactin receptors and marked suppression of serum testosterone levels. The possibility that such direct effects of GnRH agonists on testicular function could be expressed through specific receptors located in the interstitial cells of the testis was supported by the selective concentration of a 125I-labeled GnRH agonist by the testis in vivo. Specific receptors for the releasing hormone were demonstrated in testis particles and dispersed interstitial cells by direct binding analysis with the 125I-labeled GnRH agonist. The binding affinity (Ka = G X 10(9) M-1) and peptide specificity of the testicular GnRH binding sites were similar to those of anterior pituitary and ovarian GnRH receptors. The presence of GnRH receptors in the testis indicates that these sites mediate the direct inhibitory actions of GnRH agonists upon testicular endocrine function. PMID- 6254028 TI - Possible role of distinct morphine and enkephalin receptors in mediating actins of benzomorphan drugs (putative kappa and sigma agonists). AB - The binding of many opiates and enkephalins to enkephalin (delta) and morphine (mu) receptors was compared by using three different binding assays: (i) 125I labeled[D-Ala2, D-Leu5]enkephalin or 125I-labeled[D-Ala2,N-Me-Phe4,Met(O)5ol] enkephalin to brain membranes; (ii) [3H]ethylketocyclazocine to brain membranes; and (iii) [3H]diprenorphine and [3H]naloxone to neuroblastoma cell and brain membranes, respectively. According to their relative binding potencies and the effects of Na+ and GTP on the binding to these two receptors, opiates and enkephalins can be classified into seven classes: (i) morphine-type mu agonists; (ii) enkephalin-type delta agonists; (iii) mixed agonists-antagonists; (iv) putative kappa agonists; (v) putative sigma agonists; (vi) nalorphine-type antagonists; and (vii) opiate antagonists. Studies with [3H]ethylketocyclazocine do not reveal specific kappa receptors distinct from those already described that bind morphine and enkephalins. The benzomorphan analogs ketocyclazocine and ethylketocyclazocine (putative kappa agonists) and N-allylnormetazocine (putative sigma agonist) bind to morphine (mu) and enkephalin (delta) receptors with similarly high affinities. The potency of putative kappa agonists, measured by competition with binding of the 3H-labeled antagonist, is greatly reduced by the presence of Na+ and GTP; the "Na+ and GTP ratios" are similar to those of morphine and enkephalins. However, Na+ and GTP greatly decrease the potency of binding of putative sigma agonists to enkephalin receptors but only slightly decrease the binding to morphine receptors. These data suggest that putative kappa agonists have agonistic activity toward both receptors, whereas putative sigma agonists behave as agonists for enkephalin receptors but have antagonist activity for morphine receptors. Mixed agonist-antagonists also show smaller difference in affinity to both receptors. These findings may have important implications for understanding the differences in the pharmacological effects of these drugs. PMID- 6254029 TI - Integration in vivo into simian virus 40 DNA of a sequence that resembles a certain family of genomic interspersed repeated sequences. AB - The isolation and characterization of a viable mutant of simian virus 40 (SV40) called "in1449" are described. the mutant DNA is found to have a 157-nucleotide long insertion at map position 0.649 within the 5' untranslated sequence of the early region of SV40. The complete nucleotide sequence of the insert is presented. Sequence comparisons show that the insert is not of SV40 origin. The insert is presumably of monkey origin since in1449 was produced within monkey kidney cells. The sequence of the in1449 insert matches remarkably well with sequences of a certain predominant family of interspersed repeated sequences in human DNA (called the Alu family) and cloned members thereof. This high degree of sequence homology suggests that the in1449 insert is derived from a member of a family of interspersed repeated sequences in monkey DNA related to the human Alu family. The in1449 insert (and the Alu family members) contain certain oligonucleotide sequences that also are found conserved in the replication origins of papovaviruses and certain other oligonucleotides found in repetitive double-stranded regions of mammalian heterogeneous nuclear RNAs. Sequences around the two recombinant joints in in1449 exhibit a definite pattern of homology. An octanucleotide present in the SV40 part of the first recombinant joint is exactly repeated 15 nucleotides away within the insert; another octanucleotide present within the insert at the second joint is exactly repeated 21 nucleotides away in the viral DNA. The viral DNA sequences flanking the insert in in1449 also exhibit some homology. PMID- 6254030 TI - Ouabain-binding-site photoaffinity probes that label both subunits of Na+,K+ ATPase. AB - 4"'-Diazomalonyldigitoxin and its isomer, 3"'-diazomalonyldigitoxin, have been synthesized at high specific radioactivity and used as photolabels for the Na,K ATPase (ATP phosphohydrolase, EC 3.6.1.3) purified from Electrophorus electricus. Photoaffinity labeling experiments using both type I and type II complexes of enzyme with both photolabels showed ouabain-protectable labeling of the alpha as well as the beta subunit. These data suggest that, in the purified eel enzyme, the alpha and beta subunits are in intimate contact, at least in the region of the third digitoxose of the "sugar-specific" binding site. PMID- 6254031 TI - Genomic organization of rat prolactin and growth hormone genes. AB - Five overlapping cloned DNAs containing the rat prolactin gene and its flanking sequences, as well as one cloned DNA containing the rat growth hormone gene and its flanking sequences, were isolated from a chromosomal DNA library. They were characterized by restriction enzyme mapping and electron microscopy. In each gene, the structural gene sequence coding for mature mRNA of a length of about 1 kilobase is split into at least five segments by a minimum of four intervening sequences. The two genes are similar in the length and organization of their coding regions, consistent with the suggestion that they are derived from a common ancestral gene. However, the two genes differ greatly in the lengths of their intervening sequences. That leads to a total gene length of 10 kilobase pairs for the prolactin and 2.1 kilobase pairs for the growth hormone gene. At least one intervening sequence appears to be in the 5' nontranslated regions of the prolactin and growth hormone mRNA coding sequences. PMID- 6254033 TI - Amino acid sequence of the T4 DNA helix-destabilizing protein. AB - The primary structure of the T4 single-stranded DNA-binding protein coded by gene 32 has been determined by manual and autoated sequencing of peptides derived from partial proteolysis, cyanogen bromide cleavage, and digestion with trypsin, chymotrypsin, and staphylococcal protease. Tryptic digestion of citraconylated or succinylated gene 32 protein yields five peptides containing 4, 27, 42, 65, and 163 residues, which can be separated by Sephadex chromatography. Each of the tryptic peptides was subjected to automated sequencing and, if necessary, more extensive cleavage. The intact protein contains 301 amino acids, has a molecular weight of 33,487, and can be specifically cleaved at lysines 21 and 253 by limited trypsin digestion. Previous studies have shown that the "B" region (residues 1-21), which has a charge of +4, is important for the protein-protein interactions involved in gene 32 protein self-association and cooperaive binding to single-stranded DNA. The "A" region (residues 254-301) has been implicated in controlling the helix-destabilizing "activity" of gene 32 protein and in interacting with other T4 DNA replication proteins. The A region has a charge of 10 and, in addition, contains two unusual stretches of four serine residues separated by glycine 284. The region between positions 73 and 115 contains 75% of the tyrosine residues and may be important for DNA binding. PMID- 6254032 TI - Apurinic/apyrimidinic endonucleases in repair of pyrimidine dimers and other lesions in DNA. AB - The characteristics of the nicks (single-strand breaks) introduced into damaged DNA by Escherichia coli endonucleases III, IV, and VI and by phage T4 UV endonuclease have been investigated with E. coli DNA polymerase I (DNA nucleotidyltransferase). Nicks introduced into depurinated DNA by endonuclease IV or VI provide good primer termini for the polymerase, whereas nicks introduced into depurinated DNA by endonuclease III or into irradiated DNA by T4 UV endonuclease do not. This result suggests that endonuclease IV nicks depurinated DNA on the 5' side of the apurinic site, as does endonuclease VI, whereas endonuclease III has a different incision mechanism. T4 UV endonuclease also possesses apurinic endonuclease activity that generates nicks in depurinated DNA with low priming activity for the polymerase. The priming activity of DNA nicked with endonuclease III or T4 UV endonuclease can be enhanced by an additional incubation with endonuclease VI and, to a lesser extent, by incubation with endonuclease IV. These results indicate that endonuclease III and T4 UV endonuclease (acting upon depurinated and irradiated DNA, respectively) generate nicks containing apurinic/apyrimidinic sites at their 3' termini and that such sites are not rapidly excised by the 3' leads to 5' activity of DNA polymerase I. However, endonuclease IV or VI apparently can remove such terminal apurinic/apyrimidinic sites as well as cleave on the 5' side of the unnicked sites. These results suggest roles for endonucleases III, IV, and VI in the repair of apurinic/apyrimidinic sites as well as pyrimidine dimer sites in DNA. Our results with T4 UV endonuclease suggest that the incision of irradiated DNA by T4 UV endonuclease involves both cleavage of the glycosylic bond at the 5' half of the pyrimidine dimer and cleavage of the phosphodiester bond originally linking the two nucleotides of the dimer. They also imply that the glycosylic bond is cleaved before the phosphodiester bond. PMID- 6254034 TI - Solubilization of active opiate receptors. AB - Receptors that reversibly bind opiates and opioid peptides have been solubilized from brain and neuroblastoma-glioma hybrid cell NG108-15 membranes. Active receptors are specifically solubilized with a new type of detergent 3-[(3 cholamidopropyl)dimethylammonio]-1-propanesulfonate, which is a zwitterionic derivative of cholic acid. The solubilized receptor complexes behave as large molecules with a Stokes radius of 70 A and contain protein as an essential constituent. PMID- 6254035 TI - Adrenocorticotropic hormone increases specific proteins of the mitochondrial fraction that are translated inside or outside this organelle in cultured adrenal tumor cells. AB - In addition to its stimulatory effects on steroidogenesis, adrenocorticotropic hormone (ACTH) also has a trophic action on the adrenal cell. This is manifested in part by increases in the levels of key mitochondrial steroidogenic enzymes. The mechanism by which this trophic action of ACTH occurs has been studied in monolayer cultures of mouse adrenal cortical tumor cells. ACTH treatment of these cells stimulates the relative incorporation of amino acids into at least eight specific proteins in mitochondrial preparations. Two of these ACTH-responsive proteins are among the nine major adrenal polypeptides that fulfill the criteria of mitochondrial translation products: (i) their synthesis in intact cells is specifically resistant to inhibition by cycloheximide yet uniquely sensitive to chloramphenicol and (ii) they are synthesized in vitro by isolated mitochondria. The other six ACTH-responsive proteins are within the much larger category of mitochondrial proteins that are synthesized on cytoplasmic ribosomes. One of the proteins synthesized in the cytoplasm electrophoretically comigrates with purified beef adrenodoxin reductase and another with beef adrenodoxin. These findings indicate that ACTH regulates the synthesis (and turnover, or both) of specific mitochondrial proteins that are synthesized inside as well as outside the mitochondria of these adrenal cells. PMID- 6254036 TI - Polycistronic vesicular stomatitis virus RNA transcripts. AB - A procedure to enrich for the sequences present at the junction between the linked messages in the polycistronic RNAs symthesized in vitro by vesicular stomatitis virus (VSV) is described. Analyses of these sequences show that they contain a precise transcript of both the intercistronic dinucleotide and the pentanucleotide 5'--C-U-G-U-U--3', common to the 5'-end of all VSV cistrons, covalently linked to the 3'-side of the intervening poly(A). The data strongly suggest that the VSV transcriptase polyadenylylates the mRNAs and can then resume direct and precise transcription of the genome-without reinitiation and without skipping nucleotides. PMID- 6254037 TI - Mapping of transforming region of the Harvey murine sarcoma virus genome by using insertion-deletion mutants constructed in vitro. AB - Circular DNA intermediates of Harvey murine sarcoma virus (Ha-MuSV) have been cloned in lambda gtWES . lambda B and shown to be capable of transforming mouse NIH 3T3 cells [Hager, G. L., Chang, E. H., Chan, H. W., Garon, C. F., Israel, M. A., Martin, M. A., Scolnick, E. M. & Lowy, D. R. (1979) J. Virol. 31, 795-809]. By using the cloned Ha-MuSV DNA insert as a parental genome, we have constructed a series of insertion-deletion mutants by inserting an octomer containing the Sal I linker sequence (G-G-T-C-G-A-C-C) into various regions of the Ha-MuSV genome after partial digestion with Hae III. After ligation into lambda gtWES . lambda B Sal I vector molecules, the mutant Ha-MuSV DNAs were cloned. Fourteen insertion deletion mutants have been mapped by restriction enzyme digestion, and their biological activities have been correlated with the locations of mutations. The mutants whose lesion mapped within 3.0 kilobases (kb) frm the 3'-end of the Ha MuSV genome retained full transforming ability. The mutants containing the Sal I linker insertion at 0.4 or 1.5 kb from the 5'-end also retained transforming ability, but the number of foci induced by the DNAs in transfection assays was greatly reduced. However, a mutant containing a deletion of 1.5 kb at the 5'-end and a mutant with a deletion of the sequences between 1.0 and 1.5 kb from the 5' end completely lost their transforming potential. A model for the transforming region of Ha-MuSV is discussed. Furthermore, because Ha-MuSV sequences can be rescued from the mouse cells transformed by these mutants using Moloney murine leukemia virus as a helper virus, it implies that the in vitro modified DNAs may be converted into genuine mutant viruses. PMID- 6254038 TI - Surface charge changes in purple membranes and the photoreaction cycle of bacteriorhodopsin. AB - The surface potential of purple membrane fragments, determined from the distribution of the aqueous free and the membrane-bound positively charged, paramagnetic, amphiphilic probe 4-(dodecyldimethylammonium)-1-oxyl-2,2,6,6 tetramethylpiperidine bromide varied almost 60 mV as a function of ionic strength and 50 mV as a function of pH of the medium. Light-induced changes in surface potential followed the changes observed in the M412 intermediate of the photocycle of bacteriorhodopsin as a function of pH, temperature, and response to antibiotics beauvericin and valinomycin. The number of induced charges per M412 appearing at the surface of purple membranes decreased from about 0.75 to 0.45 as the surface potential became more negative. The stoichiometry would be twice as large if the charge changes were localized exclusively on one side of the purple membrane. Laser flash-induced kinetics of the rise and decay of surface charge changes were slightly slower than the kinetics of the rise and decay of M412 which is associated with the reversible deprotonation of the retinal Schiff base nitrogen in the chromophore. It is suggested that the light-induced charge changes monitor a dissociable amino acid residue which may be a step in the movement of protons across the purple membrane. PMID- 6254039 TI - Similarities and dissimilarities between calmodulin and a Chlamydomonas flagellar protein. AB - A protein that resembles vertebrate calmodulins and troponin C has been isolated from Chlamydomonas flagella by using a calmodulin purification protocol that included calcium-dependent affinity-based adsorption chromatography on phenothiazine-Sepharose conjugates. The flagellar protein resembled calmodulin in elution from reverse-phase columns, had a peptide map similar to that of calmodulin, and competed with vertebrate calmodulin in a radioimmunoassay using antisera against vertebrate calmodulin. However, this flagellar protein did not activate phosphodiesterase, lacked N epsilon-trimethyllysine, and had an isoelectric point approximately 0.3 pH unit higher than that of vertebrate calmodulin. When analyzed by polyacrylamide gel electrophoresis under various conditions, the Chlamydomonas protein migrated between vertebrate calmodulins and rabbit skeletal muscle troponin C and did not manifest a large calcium-dependent mobility shift. This calmodulin-like protein was identified as one of the approximately 200 35S-labeled components in Chlamydomonas flagella resolved by two-dimensional gel electrophoresis. These studies indicate that calmodulin and a structurally and functionally homologous protein are present in the same cell. These studies also demonstrate that caution is necessary: (i) in identifying a protein as a calmodulin, (ii) in using phenothiazines or antisera directed against vertebrate calmodulins as specific probes for calmodulin, and (iii) in the interpretation of experiments on biological systems in which calmodulin is substituted for the homologous calmodulin-like protein. PMID- 6254040 TI - Desensitization of enucleated cells to hormones and role of cytoskeleton in control of normal hormonal response. AB - Prostaglandin E1 and the beta-adrenergic hormone l-isoproterenol stimulated cyclic AMP formation in both nucleated and enucleated myeloid leukemic cells that could be induced to differentiate normally to mature cells by the macrophage- and granulocyte-inducing protein MGI (MGI+D+ cells). Enucleated as well as nucleated MGI+D+ cells also desensitized to these hormones, indicating that this desensitization is an extranuclear process. Nucleated or enucleated mutant myeloid leukemic cells that are not induced to differentiate (MGI-D- cells) were not desensitized to these hormones. The antitubulin alkaloids colchicine and vinblastine, but not the antimicrofilament compound cytochalasin B, increased the maximal hormone-induced formation of cyclic AMP in nucleated MGI+D+ cells but not in the MGI-D- cells. These alkaloids also inhibited the development of desensitization to l-isoproterenol and prostaglandin E1 in enucleated MGI+D+ cells. The results indicate that in MGI+D+ cells the cytoskeletal system puts constraints on the cells' ability to respond to these hormones and that these constraints are absent in the mutant MGI-D- cells. Because MGI+D+ but not MGI-D- cells can be induced to differentiate by the macrophage- and granulocyte-inducing protein, cytoskeletal constraints, which are also found in normal myeloid cells, may be necessary for cell competence to differentiate. The results support the suggestion that membrane cytoskeletal constraints generate may control the normal response and desensitization to membrane-mediated cell inducers. PMID- 6254041 TI - Genetic recombination of bacterial plasmid DNA: electron microscopic analysis of in vitro intramolecular recombination. AB - a tetramer of pMB9 DNA containing a single EcoRI site per tetramer was used to investigate intramolecular recombination in Escherichia coli. When transformed into wild-type E. coli strains, the tetramer was converted into dimers and a small proportion of trimers and monomers. The conversion was blocked in recA strains and rec B recC recF strains but not in recB recC strains or recF strains. Extracts of E. coli converted the tetramer into dimers, trimers, and monomers. Figure of 8 molecules and catenanes were minor products. The proportion of recombinant molecules ranged from 7% to 14%. Intramolecular recombination in vitro was blocked in extracts of recA strains and recB recC recF strains but not significantly blocked in extracts of recB recC strains and recF strains. recA protein restored activity to recA extracts; activity in recB recC recF extracts was restored by purified exonuclease V (recBC nuclease) or a recF protein donor extract. Novobiocin and oxolinic acid inhibited the reaction by 70-80%. PMID- 6254042 TI - Cotransfer of circular and linear prokaryotic and eukaryotic DNA sequences into mouse cells. AB - We have attempted to introduce some eukaryotic and prokaryotic DNA sequences into mouse fibroblasts. Purified herpes thymidine kinase gene (tk) was introduced into mouse cells. The presence of the herpes tk gene was established by gel electrophoresis, sensitivity to the purine analog acyloguanosine, and Southern blot hybridization. We utilized two different methods to introduce nonselectable markers into mouse cells. Bacterial plasmid pBR322 was ligated to herpes tk and used for transfection. All cells that were TK+ also contained the plasmid sequences. In the second method, pBR322 DNA was mixed with herpes tk DNA and presented to mouse cells. TK+ cells were tested for pBR322 sequences by blot hydridization. The frequency of unlinked cotransfer was greater than 40%. When the circular plasmid containing pBR322 and tk was used for transfection, each of the resulting transfectants acquired several copies of the plasmid. Most of the copies were associated with high molecular weight DNA in the cell. In addition, we found that some of the plasmid molecules may exist as free circular molecules. Using the nonligated cotransfer method, we introduced purified human beta-globin sequences into the recipient cells. We were unable to detect any transcripts of the human beta-globin gene at a level greater than or equal to 10 molecules per cell. PMID- 6254043 TI - Indiscriminate recombination in simian virus 40-infected monkey cells. AB - DNA transfection of African green monkey BSC-1 cells with simian virus 40 (SV40) DNA and bacterial virus phi X174 replicative form DNA ("cotransfection") yielded stocks containing SV40/phi X174 recombinant virus, which was detected by an infectious-center in situ plaque hybridization procedure and which was sensitive to anti-SV40 antiserum. The recombinant virus replicated during serial passage. Restriction endonuclease cleavage of the SV40/phi X174 DNA indicated that several different types of recombinant DNA structures had arisen. Similar SV40 DNA cotransfection experiments with polyoma virus DNA, bacterial plasmid (pBR322) DNA, and a plasmid-cloned segment of the mouse genome (coding for intracisternal type A particles) yielded stocks that generated recombinant plaques as judged by in situ plaque hybridization with the appropriate labeled probe. It appears, therefore, that an active indiscriminate recombination process, incapable of distinguishing between diverse DNAs of prokaryotic and eukaryotic origin, occurs in SV40-infected monkey cells. PMID- 6254044 TI - Germ-line reinsertions of AKR murine leukemia virus genomes in Akv-1 congenic mice. AB - Congenic mouse strains NIH,Akv-1 and NIH,Akv-2 carry the two high ecotropic virus inducing loci of the AKR mouse on the NIH Swiss genetic background. Progeny tests of animals in three separate congenic families show that both Avk-1 and Akv-2 are stably transmitted as classical mendelian loci in these mice. However, during the process of inbreeding, additional chromosomal viral loci were detected in several NIH.Akv-1 sublines. These loci appeared only in the progeny of virus-positive females. They segregate with mendelian ratios, are unlinked to markers on chromsome 7 near Akv-1, and are phenotypically expressed as high-virus-inducing loci. The generation of new loci for viurs induction, no doubt resulting from the rare germ-line reintegration of the endogenous ectropic provirus, represents a unique form of gene duplication and rearrangement. PMID- 6254045 TI - DNA-transformed murine teratocarcinoma cells: regulation of expression of simian virus 40 tumor antigen in stem versus differentiated cells. AB - Thymidine kinase-deficient (TK-; ATP:thymidine 5'-phosphotransferase, EC 2.7.1.21)F9 teratocarcinoma stem cells have been transformed with a recombinant plasmid genome consisting of the pBR322 genome linked to a herpes simplex virus type 1 thymidine kinase gene (HSV-1 tk) and a simian virus 40 (SV40) genome. A clonal line of stem cells was obtained that contains only one copy of plasmid DNA, which is integrated into murine chromosomal DNA through a site on the pBRR322 genome. The HSV-1 tk gene, which is adjacent to the SV40 genome, is expressed in stem cells, whereas SV40 gene expression is not detectable. If differentiation of these stem cells is induced, the differentiated cells express SV40 early gene products. Thus, we have constructed a stem cell which contains a set of genes (SV40), the expression of which is regulated differently in stem and differentiated cells. This cell line could be used to determine the mechanism of suppression of expression of these genes in stem cells. PMID- 6254046 TI - Control of gene expression by a mobile recombinational switch. AB - Transposable recombinational switches may play important roles in the evolution of bacterial populations by increasing flexibility in the control of expression of particular genes and thereby maintaining heterogeneity in clones of cells growing in a uniform environment. Experiments reported here show that Tn5-112, a deletion derivative of kanamycin-resistance transposon Tn5, can function as such a mobile recombinational switch. The internal deletion in Tn5-112 removes transcription termination signals and permits transcription initiated within the element to continue into nearby bacterial genes. Consequently, in one orientation Tn5-112 stimulates distal gene expression, whereas in the other orientation the normal polarity imposed by wild-type Tn5 intervenes and distal gene expression is not stimulated. Because Tn5-112 contains terminal inverted repeats, intramolecular recombination can invert the Tn5-112 element and alter gene expression. Tn5-112 is transposition deficient. Its mobility derives from the recessive nature of the transposition deficiency and, in this study, from the possibility of homologous recombination which permits its placement in either orientation at any site occupied by nother Tn5 element. PMID- 6254048 TI - Induction of lymphoma in athymic mice: a model for study of the human disease. AB - A murine lymphoma, designated L1, was produced in immunologically deficient nude mice after chronic antigenic stimulation by infection with the pinworms Aspiculuris tetraptera and Syphacia obvelata. In vivo, L1 involves primarily the spleen and lymph nodes, with infiltration of liver, kidney, and bone marrow also observed. It is characterized by large clusters of B cells and null cells, and by rare T cells. The lymphoma cells express murine leukemia virus antigens (gp70 and p30) on the surface. L1 can be passaged successfully both in vivo and in vitro. The lymphoblasts that proliferate in vitro are null, but injecton back into the mouse produces a similar pattern of B cells, null cells, and occasional T cells as seen in the mouse-to-mouse transfers. Infectious viruses have been isolated from L1 cells and from tissue culture supernates and have been identified as a B tropic murine leukemia virus and a xenotropic virus. The possibilities of this model for studying the etiology of human lymphoma are discussed. PMID- 6254047 TI - Structural organization of human genomic DNA encoding the pro-opiomelanocortin peptide. AB - We have isolated a human genomic DNA segment encoding the corticotropin-beta lipotropin precursor peptide from a fetal DNA library, using previously cloned bovine cDNA for this peptide as a probe. The human genomic DNA was studied by electron microscope heteroduplex analysis and gel blotting methods, and its nucleotide sequence was determined and compared with that of cDNA corresponding to bovine pro-opiomelanocortin mRNA. From this sequence, segments of interspecies conservation and divergence, punctuated by pairs of the basic amino acid residues lysine and arginine, were identified. No noncoding intervening sequence was observed over an 830-base-pair DNA segment extending from a position near the 5' end of the structural pro-opiomelanocortin gene through the 3' terminus of the cDNA and including sequences for the component peptide hormones corticotropin and beta-lipotropin. PMID- 6254049 TI - Appearance of cytoskeletal components on the surface of leukemia cells and of lymphocytes transformed by mitogens and Epstein-Barr virus. AB - Lactoperoxidase iodination and two-dimensional electrophoresis of the labeled proteins have demonstrated well-characterized cytoskeletal proteins (actin and tubulins) on the surface of human lymphocytes undergoing blastogenic transformation and of certain malignant human cells. Such proteins could not be detected on the surface of normal resting human lymphocytes. The most prominent cytoskeletal protein identified on the surface membrane of mitogen-transformed T and B lymphocytes was actin. In Epstein-Barr virus genome-positive Burkitt's lymphoma and lymphoblastoid cell lines and in two leukemia cells, the major iodinated membrane protein components were actin and alpha 1-, alpha 2-, and beta tubulins. These proteins were firmly connected to the cytoplasmic skeleton and could not be removed by Triton X-100. Concurrent immunofluorescence studies with specific antibodies and F(ab')2 fragments confirmed the appearance of cytoskeletal components on the biochemical data, and indicated that such cytoskeletal proteins formed distinctive patterns on the cell surface, ranging from small patches to large projections. Five-hour labeling with [35S]methionine indicates that all such cells released large quantities of labeled actin and tubulins into the culture medium. These materials were not readsorbed to the membrane surfaces of the cells. PMID- 6254050 TI - A transformation-defective mutant of Abelson murine leukemia virus lacks protein kinase activity. AB - A transformation-defective mutant of Abelson murine leukemia virus (A-MuLV), called A-MuLV-P92td, has been isolated. The mutant encodes a serologically identifiable A-MuLV protein of molecular weight 92,000 (P92) but it lacks the ability to transform either fibroblasts or bone marrow lymphoid cells. In contrast to the protein made by transforming strains of A-MuLV, the protein made by A-MuLV-P92td does not becme phosphorylated during in vitro incubation with [gamma-32P]ATP. If the protein is mixed with proteins from cells transformed by a functional A-MuLV strain, phosphorylation of P92 occurs, showing that its ability to accept phosphate is not altered by the mutation. These parallel changes provide genetic evidence that the A-MuLV protein is a transforming protein and that its associated protein kinase activity (EC 2.7.1.37) is a crucial part of its transforming ability. PMID- 6254051 TI - An attempt to distinguish between the actions of neuromuscular blocking drugs on the acetylcholine receptor and on its associated ionic channel. AB - The effects of lobeline and tubocurarine on the voltage-clamped endplates of frog sartorius and cutaneous pectoris muscles were examined at room temperature (20-23 degrees C). Like tubocurarine, lobeline causes nondepolarizing neuromuscular blockade. The half-time of decay (t((1/2))) of endplate currents (e.p.c.s) recorded at a holding potential (V(m)) of -90 mV was significantly shorter in endplates treated with lobeline (50 muM; mean t((1/2)) +/- SEM = 0.41 +/- 0.02 ms) or tubocurarine (11.4 muM; t((1/2)) = 0.64 +/- 0.04 ms) than in those treated with Mg(2+) (13 mM; t((1/2)) = 1.39 +/- 0.11 ms) or a low concentration of tubocurarine (3 muM; t((1/2)) = 0.87 +/- 0.05 ms). Similarly, lobeline (10 muM) shortened the t((1/2)) of untreated miniature e.p.c.s by 35%; tubocurarine, however, abolished miniature e.p.c.s at the concentration required to observe its actions on e.p.c. decay kinetics. The t((1/2)) of e.p.c.s recorded from preparations treated with Mg(2+) (13 mM), tubocurarine at low concentrations (3 muM), or untreated miniature e.p.c.s was logarithmically related to V(m), being slower at more hyperpolarized values. By contrast, the t((1/2))s of e.p.c.s recorded in either lobeline (50 muM) or tubocurarine (11.4 muM) were independent of voltage in the range -150 to -80 mV. The ability of lobeline to shorten t((1/2)) and to remove the voltage dependence of t((1/2)) was partially antagonized by Mg(2+) (13 mM). As expected, when lobeline or tubocurarine was removed from the bath or when acetylcholine release from the motor nerve terminals was increased by 4-aminopyridine (20 muM) and Ca(2+) (10 mM) (in the presence of lobeline or tubocurarine), the amplitude of e.p.c.s increased as a function of time. However, the t((1/2)) of the decay phase of the e.p.c.s remained shortened (i.e., unaltered from the earlier treatment). These results suggest that both tubocurarine and lobeline have at least two distinct postjunctional actions including: (i) a block of the acetylcholine receptor and (ii) a block of the ionic channel associated with the acetylcholine receptor. PMID- 6254052 TI - Further evidence for peptidergic transmission in sympathetic ganglia. AB - We previously proposed that, in sympathetic ganglia of the bullfrog, a peptide which resembles luteinizing hormone-releasing factor (LH-RF, luliberin) functions as the transmitter for the late slow excitatory postsynaptic potential (epsp), a signal that may last 5-10 min. To test this hypothesis further, we have compared the physiological andpharmacological effects of LH-RF with those of the natural transmitter and have found a close parallel. (i) LH-RF, when ejected with a brief pulse of pressure through a micropipette near a ganglion cell, produces a depolarizing response lasting for minutes. (ii) The LH-RF-induced response is associated with changes in input resistance similar to thoe during a late slow epsp. (iii) The amplitudes of the LH-RF-induced response and the late slow epsp vary in parallel as the membrane potential is shifted over a wide range. (iv) Both responses increase the excitability of ganglion cells. (v) The two responses interact with the cholinergic epsps in a parallel manner: they cause diminution of the slow epsp but not of the fast epsp. (vi) Both responses are blocked by an analog of LH-RF that antagonizes the effects of LH-RF in the rat. PMID- 6254053 TI - Serotonin-induced hyperpolarization of an indentified Aplysia neuron is mediated by cyclic AMP. AB - Addition of serotonin to the medium bathing an Aplysia abdominal ganglion causes a change in the endogenous bursting activity of the identified neuron R15. At serotonin concentrations in the micromolar range, the predominant effect is an increase in depth and duration of the interburst hyperpolarization and consequent decrease in burst rate. At higher concentrations (10 microM) serototin can inhibit bursting completely. We have shown previously that these changes can be mimicked by bath application or intracellular injection of several cyclic AMP analogs substituted at the 8 position. Voltage clamp analysis indicates that serotonin and cyclic AMP analogs both cause an increase in membrane slope conductance in R15, with reversal potentials for the responses between -75 and 80 mV, close to the K+ equilibrium potential. When the K+ concentration in the bathing medium is changed, the reversal potentials change in a manner suggesting that serotonin and cyclic AMP analogs on K+ conductance are not additive. Furthermore, the effects of low concentrations of serotonin can be potentiated by the phosphodiesterase inhibitor Ro 20-1724. A pharmacological analysis indicates that the serotonin receptor that mediates hyperpolarization in R15 is similar to the serotonin receptor that we have shown to be coupled to adenylate cyclase. The present electrophysiological and pharmacological observations, together with our previous biochemical and pharmacological results, demonstrate that the serotonin induced hyperpolarization of neuron R15 is mediated by cyclic AMP. PMID- 6254054 TI - Nucleotide sequence of influenza virus RNA segment 8 indicates that coding regions for NS1 and NS2 proteins overlap. AB - The smallest RNA segment of influenza A viruses (vRNA segment 8) has recently been shown to code for two unrelated nonstructural proteins (NS1 and NS2) translated from separate mRNAs. Molecular weight considerations indicated that there might not be enough space on vRNA segment 8 for the two coding regions unless they overlap. We have recently cloned in bacterial plasmids several genes of an avian influenza A virus, fowl plague virus (EPV), and now present the complete nucleotide sequence of FPV RNA segment 8 largely determined from the cloned DNA. The DNA sequence predicts two open protein synthesis reading frames that can be translated into polypeptides of sizes similar to those of NS1 and NS2. The coding regions for these polypeptides overlap by the equivalent of 43-60 amino acids, the exact amount depending on which of several possible methionines initiates the synthesis of NS2. PMID- 6254055 TI - Nucleosomal packaging of the thymidine kinase gene of herpes simplex virus transferred into mouse cells: an actively expressed single-copy gene. AB - We have studied the nucleoprotein structure of the herpes thymidine kinase gene introduced into mouse Ltk-aprt- cells by means of DNA-mediated gene transfer. Using the technique of Southern blotting, we examined staphylococcal digests of the nuclei from the relatively stable transformants that contain one or less integrated copies of the thymidine kinase gene per haploid genome. Out experiments show that, under selection for the active expression of this gene, it is packaged in nucleosomes with a repeat length identical to the average for the host mouse sequences. PMID- 6254056 TI - Crystallization of the middle part of the mitochondrial electron transfer chain: cytochrome bc1-cytochrome c complex. AB - Complex III (cytochrome bc1 particle; ubiquinol:ferricytochrome c oxidoreductase, EC 1.10.22) was purified from beef heart mitochondria by affinity chromatography. Phospholipids were depleted by washing the particle with detergent while it still was on the affinity column. The particle first was mixed with an excess of cytochrome c in 1.5% cholate (wt/vol); slow removal of the detergent from the mixture was achieved by dialysis. Freezing of the mixture resulted in crystallization of the cytochrome bc1 particle in the form of a 1:2 complex with cytochrome c. The chemical composition and spectrophotometric properties of the crystal are described. The same crystallization maneuver used in the case of cytochrome oxidase has been demonstrated to be effective in crystallizing the middle part of the mitochondrial electron-transfer chain. PMID- 6254057 TI - Reconstitution of the hepatic asialoglycoprotein receptor with phospholipid vesicles. AB - A solubilized detergent-free preparation of the hepatic binding protein specific for asialoglycoproteins associates spontaneously with small unilamellar lipid vesicles. This process is independent of the phase transition of the lipid and effectively restores the specific binding activity of the receptor protein. The insensitivity of the resulting lipid-protein complex to ionic strength provides evidence for a hydrophobic interaction. There is a perturbation of the lipid phase transition concomitant with addition of the protein. Circular dichroism studies indicate that the protein undergoes a conformational change on association with lipid. Binding of specific ligand produces further physical changes in the receptor as indicated by alterations in the tryptophan fluorescence quenching pattern. PMID- 6254059 TI - Cloning and analysis of a cDNA coding for bovine prothrombin. AB - Poly(A)-RNA enriched for prothrombin was isolated by specific immunoprecipitation of bovine liver polysomes. Prothrombin consisted of about 8% of the cell-free translation products of this RNA. A double-stranded cDNA was synthesized by using reverse transcriptase (RNA-dependent DNA nucleotidyltransferase) and made blunt ended with nuclease S1. After tailing with dCTP and terminal transferase, the double-stranded cDNA was annealed to pBR322 DNA that had been cleaved previously at the single Pst I site and similarly tailed with dGTP. The resulting plasmids were used to transform Escherichia coli strain RR1 under P3-EK1 conditions. Sixty three tetracycline-resistant clones were obtained that hybridized to 32P-labeled cDNA synthesized from prothrombin-enriched mRNA. Recombinants containing cDNA to prothrombin mRNA sequences were screened by a solution hybridization assay with a [3H]cDNA synthesized from mRNA. This enriched mRNA was 50% prothrombin mRNA, as determined by a reticulocyte lysate translation assay. Three positive clones were identified by this assay; they contained bovine DNA inserts of 700, 500, and 400 base pairs. The DNA sequence of the 700-base-pair insert was then determined. This recombinant plasmid contained DNA coding for the carboxyl-terminal 160 residues of bovine prothrombin followed by a noncoding region of 119 base pairs and a poly(A) tail of 60 base pairs. PMID- 6254058 TI - Construction of a composite tRNA gene by anticodon loop transplant. AB - By using sites for the restriction nuclease Hpa II, the information for the anticodon stem and loop of an altered Su+2 amber suppressor tRNA (a mutant of tRNAGln) has been transplanted to a specially prepared tRNATrp gene, which lacks it homologous anticodon stem and loop sequence. The resulting tRNA gene was cloned under lac operator-promoter control. The result is a functional, hybrid, amber-suppressor tRNA that can exhibit a moderately high efficiency in translation. It appears less efficient, however, than Su+7 tRNA, the amber suppressor that results from a direct anticodon mutation in tRNATrp. As judged by its suppressor spectrum, which is almost identical to the spectra of Su+2, and Su+7, the recomposed tRNA inserts glutamine at amber sites. This experiment is the prototype of a series of construction that examine the role of the nucleotides in the anticodon region. PMID- 6254060 TI - Origin and functional properties of the major gene product of the Snyder-Theilen strain of feline sarcoma virus. AB - The only known product of the Snyder-Theilen strain of feline sarcoma virus (ST FeSV) is a 85,000-dalton protein, designated ST P85, that contains feline leukemia virus gag gene encoded proteins (p15, p12, and a fragment of p30) and a sarcoma virus-specific polypeptide. Antibodies directed against the latter immunoprecipitated a 92,000-dalton phosphoprotein (NCP 92) expressed at low levels in normal feline embryo fibroblasts as well as in feline cells of epithelial or lymphoid origin. Normal cellular proteins crossreactive with ST P85 were also detected in cell lines from various other mammalian species. These results suggest that the ST-FeSV sequences encoding for the sarcoma virus specific domain of ST P85 originated from an evolutionarily conserved cellular gene expressed in cells of independent differentiation lineage. Immunoprecipitates containing ST-FeSV P85 exhibited a protein kinase activity that specifically phosphorylated tyrosine residues. The physiological significance of this finding is illustrated by the finding that phosphotyrosine is an intrinsic component of ST P85. Furthermore, 5- to-fold higher levels of this unusual phosphorylated amino acid were present in ST-FeSV transformants than in uninfected control cells. Phosphorylation of tyrosine residues appears to be associated with cellular transformation caused by Rous sarcoma virus and Abelson murine leukemia virus. Thus, independent transforming virus isolates from birds, mice, and cats may utilize common pathways in exerting their oncogenic potential. PMID- 6254061 TI - Acyclovir inhibition of Epstein-Barr virus replication. AB - Acyclovir [9-(2-hydroxyethoxymethyl)guanine] triphosphate inhibits Epstein-Barr virus (EBV)-associated DNA polymerase (DNA nucleotidyltransferase; EC 2.7.7.7) to a greater extent than it inhibits host alpha and beta DNA polymerases. The affinity of the compound for viral polymerase is 100-fold higher than for alpha polymerase. The extent of inhibition is dependent upon the base composition of the template-primer. The inhibition is prevented by increasing concentrations of deoxyguanosine triphosphate. The EBV-associated DNA polymerase reaction in the presence of the inhibitor, although depressed, proceeds at a linear rate over a long period of time. In contrast, the reaction of Escherichia coli DNA polymerase I in the presence of 2',3'-dideoxythymidine 5'-triphosphate, a DNA chain terminator, levels off after initial linearity. Preincubation of acyclovir triphosphate with DNA and enzyme does not increase its inhibitory activity. The virus-producing cell line P3HRF-1 consistently shows reduced viral genome numbers and viral capsid antigen on prolonged exposure to acyclovir. The number of EBV genomes returns to the control level when the cells are grown in drug-free medium. The results suggest that a competitive mechanism is the major mode of acyclovir inhibition of EBV replication. PMID- 6254062 TI - Novel bacteriophage lambda cloning vector. AB - A simple method for generating phage collections representing eukaryotic genomes has been developed by using a novel bacteriophage lambda vector, lambda 1059. The phage is a BamHI substitution vector that accommodates DNA fragments 6-24 kilobases long. Production of recombinants in lambda 1059 requires deletion of the lambda red and gamma genes. The recombinants are therefore spi- and may be separated from the spi+ vector phages by plating on strains lysogenic for bacteriophage P2. Random fragments suitable for insertion into lambda 1059 are obtained by partial digestion of high molecular weight eukaryotic DNA with Sau3a. This restriction enzyme cleaves at the sequence G-A-T-C and leaves a 5' tetranucleotide "sticky end." Because G-A-T-C extensions are also produced by BamHI cleavage, these fragments may be annealed directly to BamHI-cleaved lambda 1059. By using these methods, a set of clones covering the entire Caenorhabditis elegans genome was constructed. DNA segments which include the unc-54 myosin heavy chain gene have been isolated from this collection. PMID- 6254063 TI - Cellular sequences are present in the presumptive avian myeloblastosis virus genome. AB - EcoRI restriction endonuclease fragments from a lambda proviral DNA hybrid containing the entire presumptive avian myeloblastosis virus (AMV) provirus, and from a lambda proviral hybrid containing a partial myeloblastosis-associated virus type 1 (MAV-1)-like provirus were compared by heteroduplex analysis. The cloned presumptive AMV provirus was also analyzed by electron microscopy, using R loop formation with purified 35S RNA isolated from virions of the standard AMV complex. The results indicate that the putative AMV genome contains a segment absent in its MAV-1-like helper virus. This segment represents a substitution in the region of the genome that in MAV-1 virus is occupied by the envelope gene and is approximately 900 +/- 160 nucleotide pairs in length. Hybridization of specific probes from the presumptive AMV genome to Southern blots of EcoRI digested cellular DNA has revealed that these substituted sequences are homologous to chicken and duck DNA that is not related to chicken endogenous proviral sequences. PMID- 6254064 TI - In vitro DNA replication of recombinant plasmid DNAs containing the origin of progeny replicative form DNA synthesis of phage phi X174. AB - The origin of phage phi X174 progeny replicative form (RF) DNA synthesis has been inserted into the plasmid vector pBR322 and cloned. In direct contrast to pBR322, the recombinant superhelical plasmids can substitute for phi X174 RFI DNA as template in phi X174-specific reactions in vitro. We have shown that the recombinant plasmids: (i) are cleaved by the phi X174 A protein; (ii) support net synthesis of unit-length single-stranded circular DNA in the presence of the phi X174 A protein and Escherichia coli rep protein, DNA-binding protein, and DNA polymerase III elongation system; (iii) support replication of duplexes catalyzed by the phi X174 A protein and extracts of E. coli. PMID- 6254065 TI - Autoradiographic detection of animal cell membrane mutants altered in phosphatidylcholine synthesis. AB - We have screened approximately 20,000 colonies of Chinese hamster ovary cells immobilized on filter paper [Esko, J.D. & Raetz, C.R.H. (1978) Proc Natl. Acad. Sci. USA 75, 1190-1193] for strains unable to incorporate [methyl-14C]-choline into trichloroacetic acid-precipitable phospholipid at 40 degrees C. Mutant 58, identified in this way, was specifically defective in choline incorporation, and other isolates were also blocked in thymidine and leucine incorporation into DNA and protein, respectively. Further analysis of mutant 58 revealed that the strain grew almost normally at 33 degrees C, the permissive temperature, but divided only once at 40 degrees C, the restrictive temperature. After a 20-hr incubation at 40 degrees C, the phosphatidyl-choline level dropped from 41% to 20% in the mutant whereas other phospholipids, including sphingomyelin, continued to accumulate. Wild-type cells contained approximately 50% phosphatidylcholine at both temperatures. Anion-exchange chromatography of the water-soluble choline metabolites extracted from mutant 58 revealed that phosphorylcholine accumulation increased from 6 nmol/mg of protein at 33 degrees C to 42 nmol/mg of protein at 40 degrees C whereas CDP-choline decreased from 0.42 nmol to less than 0.07 nmol per mg of protein. Phosphorylcholine also increased in wild-type cells shifted from 33 degrees C to 40 degrees C (from 1.8 nmol to 16 nmol per mg of protein), but the level of CDP-choline was not altered (from 0.52 nmol to 0.58 nmol per mg of protein). Enzymatic assays of extracts prepared from mutant and wild-type cells revealed a reduction of CTP: phosphorylcholine cytidylyltransferase (EC 2.7.7.15) activity (CDP-choline synthetase) in the mutant to 1/40th that in the wild type, and mixing experiments excluded the production of antagonists to CDP choline synthesis in the mutant. Thus, the inability of the mutant to generate normal amounts of phosphatidylcholine in vivo was correlated with an enzymatic lesion in the biosynthesis of CDP-choline in vitro. PMID- 6254067 TI - Processing of the precursor to corticotropin and beta-lipotropin in humans. AB - The biosynthesis of human corticotropin (ACTH) was studied in organ culture of pituitary adenomas and by translating mRNA from an ectopic ACTH-producing tumor in a cell-free system. Peptides similar to human ACTH, beta-lipotropin, and the amino-terminal glycopeptide are cleaved from a common precursor with an apparent molecular weight of 35,000 on sodium dodecyl sulfate/polyacrylamide gels. The precursors synthesized in pituitary and ectopic ACTH-producing tissues are indistinguishable. The cleavage sites of the peptide chain appear to be similar to those previously deduced for murine and bovine ACTH. Immunoprecipitation studies suggest that the primary structure of the precursor peptide is similar in all three species. However, glycosylation is different in the human and murine precursors: the precursor to human ACTH appears to be glycosylated only in the amino-terminal fragment, not in the ACTH or beta-lipotropin sequences. Studies with an autopsied normal human pituitary suggest that neither normal nor adenomatous pituitary tissue glycosylates the ACTH sequence. PMID- 6254066 TI - Antibodies specific for the carboxy- and amino-terminal regions of simian virus 40 large tumor antigen. AB - Antibodies specific for the amino- and carboxy-terminal portions of simian virus 40 large tumor (T) antigen were obtained by immunization of rabbits with synthetic peptides corresponding to these regions. The amino-terminal synthetic peptide has the sequence Ac-Met-Asp-Lys-Val-Leu-Asn-Arg-(Tyr). The tyrosine residue was introduced in order to couple the peptide to bovine serum albumin with bis-diazotized benzidine. The carboxy-terminal peptide has the sequence Lys Pro-Pro-Thr-Pro-Pro-Pro-Glu-Pro-Glu-Thr. It was coupled to bovine serum albumin with glutaraldehyde. The antisera against both peptides reacted with large T antigen. The specificity of the immune reaction was demonstrated by inhibition experiments using excess synthetic peptides. Furthermore, fragments of T antigen encoded by the nondefective adenovirus 2-simian virus 40 hybrid viruses Ad2+ND2 and Ad2+ND4, which contain the carboxy terminus and lack the amino terminus of large T antigen, were precipitated only with antiserum to the carboxy-terminal peptide. Small T antigen was not precipitated with either serum, suggesting that the amino terminus of small T antigen has a conformation different from that of large T antigen or that it is sterically hindered by a host protein. The procedures used here are of general importance for identification and characterization of gene product. PMID- 6254068 TI - Origin of DNA replication of bacteriophage f1 as the signal for termination. AB - Restriction fragments that contain the origin of DNA replication of bacteriophage f1 were inserted in vitro into circular f1 DNA molecules to form genomes that contain two origins. This DNA was used to transfect Escherichia coli. Analyses of the DNA of the progeny phage indicated that one origin and the DNA segment located between the two origins in the infecting DNA molecules had been eliminated. This result is interpreted to mean that the nucleotide sequence of the origin for plus (viral)-strand synthesis also serves as the signal for the termination of DNA synthesis. PMID- 6254070 TI - Electron paramagnetic resonance spectroscopy of Cu2+ in hen egg-white lysozyme. AB - We have obtained the electron paramagnetic resonance spectrum of Cu2+ bound in a tetragonal single crystal of hen egg-white lysozyme. A part of this spectrum has been shown to originate from Cu2+ ions bound at the site designated as B by Teichberg et al. [Teichberg, V.I., Sharon, N., Moult, J., Smilansky, A. & Yonath, A. (1974) J. Mol. Biol. 87, 357-368]. The values of the spin hamiltonian parameters that describe this part of the spectrum are reported. The implications of these values with respect to the chemical nature and configuration of ligands are discussed. The other features of the spectrum are also described. PMID- 6254069 TI - Nucleotide sequence analysis of the transforming region and large terminal redundancies of Moloney murine sarcoma virus. AB - The sequence of the transforming region of the Moloney murine sarcoma virus genome has been determined by using molecularly cloned viral DNA. This region, 3.6 to 5.8 kilobase pairs from the left end of the molecule, contains the entire cellular insertion (src) sequence as well as helper viral sequences including the large terminal repeat (LTR). On the viral RNA strand, a long (1224 bases) open reading frame commenced to the left of the src-helper virus junction and terminated at a point 58 nucleotides into helper viral sequences to the right of src. Possible promoter and acceptor splice signals were detected in helper viral sequences upstream from this open reading frame. On the antiviral RNA strand, several promoter-like sequences, including one within the src region itself, were identified. However, no open reading frame downstream from these promoters was detected in the antiviral RNA strand. The LTR was found to contain promoter-like sequences as well as LTR was found to contain promoter-like sequences as well as mRNA capping and polyadenylylation signals. In addition, it possessed an 11-base inverted terminal repeat at each end. Thus, the structure of the Moloney murine sarcoma virus genome with an LTR at each end resembles that of prokaryotic transposable elements. PMID- 6254071 TI - Transforming growth factors produced by certain human tumor cells: polypeptides that interact with epidermal growth factor receptors. AB - Three different human tumor lines in culture, a rhabdomyosarcoma, a bronchogenic carcinoma and a metastatic melanoma, release proteins (transforming growth factors, TGFs) into the medium that confer the transformed phenotype on untransformed fibroblasts. These proteins are acid and heat-stable; produce profound morphologic changes in rat and human fibroblasts; and enable normal anchorage-dependent cells to grow in agar. Removal of the transforming protein results in a reversion of cell phenotype. The major activity interacts with epidermal growth factor (EGF) cell membrane receptors. The peptides from these tumor cells are similar in their action to the sarcoma growth factor (SGF) released by murine sarcoma virus-transformed rodent cells. The most anchorage independent tumor cells released the most TGFs. EGF-related TGFs were not detectable in fluids from cultures of cells with high numbers of free EGF membrane receptors (normal human fibroblasts and human carcinomas). PMID- 6254072 TI - Cloning of an origin of DNA replication of Xenopus laevis. AB - DNA fragments of Xenopus laevis, the African frog, were cloned in the EcoRI site of the Escherichia coli plasmid pACYC189 and tested for ability to initiate and complete replication of the recombinant plasmid when injected into unfertilized eggs of X. laevis. After measurement of the [3H]-thymidine incorporation per egg for a number of recombinant plasmids, pSW14 and pSW9, which respectively contain a small segment (550 base pairs) and several kilobases of frog DNA, were selected for more extensive analysis. In spite of the small size of the segment in pSW14, it incorporates in 2 hr at least 3 times as much labeled thymidine as either pSW9 or the vector alone. The DNA synthesis in pSW14 was shown to be replication rather than repair synthesis, based on a buoyant density shift of the product when iododeoxyuridine was used for labeling. To determine the number of replications of pSW14, a novel method was employed. Because pSW14 is a head-to head dimer of the vector with the Xenopus fragment inserted at an EcoRI site, the plasmid has three methylatable sites--two bracketing the Xenopus fragment and one opposite the fragment. By cotransformation of E. coli with pSW14 and pBR322 containing the EcoRI methylase gene, supercoiled pSW14 was methylated and injected into eggs with [3H]thymidine. Disappearance of modified EcoRI sites by semiconservative replication was followed by measuring the sensitivity to EcoRI endonuclease over time. The results showed that about 50% of the labeled, supercoiled DNA recovered from eggs after 4 hr was sensitive to EcoRI digestion, which indicates that most of the DNA that incorporated [3H]thymidine had replicated twice during the 4 hr in the unfertilized eggs of X. laevis. We conclude that pSW14 has a functional origin in the Xenopus DNA segment. PMID- 6254073 TI - Monoclonal antibodies against the major glycoprotein (gp350/220) of Epstein-Barr virus neutralize infectivity. AB - Hybridomas producing antibodies against Epstein-Barr virus (EBV) have been produced. They have been screened for production of antibodies against the EBV associated membrane antigens that are present on EBV producer cell lines. For the screening test we used a double-antibody radioimmunoassay with 125I-labeled rabbit anti-mouse Ig as the second step. Positive cultures were cloned and one such clone, C1, was used for further study. C1 antibody neutralizes EBV in vitro and immunoprecipitates both gp350 (the major glycoprotein in B95-8 cells) and gp220 (the major glycoprotein in P3HR-1 cells) from the membrane antigen complex, suggesting that these molecules are antigenically related. The presence of gp350/220 both on the plasma membrane and in the cytoplasm may be detected by immunofluorescence with C1 antibody. PMID- 6254074 TI - Messenger RNA prevalence in sea urchin embryos measured with cloned cDNAs. AB - mRNA prevalence during sea urchin development was measured by treating cDNA clone colonies with labeled cDNAs transcribed from unfertilized egg and embryo poly(A) RNAs. The number of cytoplasmic transcripts per embryo complementary to several clones was determined independently by titration with poly(A)-RNA in solution, and the amount of cDNA bound to these clones in colony hybridizations was shown to be proportional to the concentration of the respective poly(A)-RNAs in the embryo cytoplasm. At the gastrula stage, the most prevalent mRNA species occur in about 10(6) molecules per embryo. If all cells were equivalent, this would be a few hundred molecules per cell. By pluteus stage, the prevalence of some sequences has increased more than 10-fold. Most, though not all, sequences prevalent in later embryos are also present in the maternal RNA of the unfertilized egg. For most poly(A)-RNA sequences, the prevalence levels determined during oogenesis are maintained through the pluteus stage, whereas a minority of sequences display sharp stage-specific changes in representation during development. PMID- 6254075 TI - Regulation of stromal cell collagenase production in adult rabbit cornea: in vitro stimulation and inhibition by epithelial cell products. AB - Media conditioned by epithelial cells from the adult rabbit cornea were capable of both stimulating and inhibiting production of latent collagenase by stromal cells from the same source. Cytochalasin B was required in this in vitro system for both secretion of stimulators by epithelial cells and production of collagenase by stromal cells in response. Optimal production of collagenase by stromal cells in response. Optimal production of stimulators occurred in low density epithelial cell cultures. Chromatographed conditioned medium from such cultures contained three stimulator fractions with apparent molecular weights of 19,000, 54,000, and greater than or equal to 90,000. High-density epithelial cell cultures secreted inhibitors of stromal cell collagenase production with apparent molecular weights of 7000 and 19,000. Cytochalasin B was not required for production of inhibitors. Inhibitory conditioned medium blocked the effect of the 19,000-dalton and 54,000-dalton stimulator on stromal cells. The data suggest that epithelial cells, in ways depending on their density, may modulate collagen degradation in the integument. PMID- 6254076 TI - Putative actin genes in the macronucleus of Oxytricha fallax. AB - Previous work has shown that the macronuclear DNA of the hypotrichous ciliate Oxytricha fallax is arranged as short achromosomal pieces, 22 to 0.5 kilobase pairs (kb) in length. Micronuclear DNA has a typical chromosomal organization. Macronuclear DNA is derived from micronuclear DNA through a process of polytene chromosome fragmentation with a resultant decrease in DNA sequence complexity. Three putative actin genes have been identified in macronuclear DNA by using a cloned yeast actin gene as a hybridization probe. A restriction fragment of the yeast gene containing both actin coding and noncoding DNA hybridizes strongly to two macronuclear DNA pieces, 1.6 and 1.4 kb in length, and weakly to a 1.2-kb piece. The entire 1.6-kb piece has been cloned in plasmid pBR322 and the resulting recombinant plasmid has been designated pOfACT(1.6). The 1.6-kb pOfACT(1.6) insert hybridizes only to those restriction fragments of the yeast actin gene containing actin coding sequences. When hybridized to macronuclear DNA under conditions that allow the yeast probe to hybridize to all three macronuclear pieces, the pOfACT(1.6) insert hybridizes only to the 1.6-kb piece. Under less stringent conditions the insert also hybridizes to the 1.4-kb piece, but it shows no hybridization to the 1.2-kb DNA. The three macronuclear pieces homologous to the yeast actin gene thus differ in sequence and are interpreted as a related family of actin genes. Each of these pieces could accommodate an actin coding sequence, which in yeast, Dictyostelium discoideum, and Drosophila melanogaster is 1.1 kb, and an additional 0.1-0.5 kb of noncoding DNA. PMID- 6254077 TI - Activation of cellular genes by avian RNA tumor viruses. AB - We demonstrated previously that chicken embryo fibroblasts accumulate approximately 100 copies of embryonic globin RNA after transformation by Rous sarcoma virus. Here we demonstrate that the globin gene in chicken embryo fibroblasts is activated by infection with two other oncogenic retroviruses, avian erythroblastosis virus and strain MC-29 of avian myeloblastosis virus, which contain transforming genes unrelated in nucleotide sequence content to each other or to the Rous sarcoma virus src gene. In addition, we have measured the genetic complexity of transformation by using established techniques for determining the number of different RNA sequences in specific populations of cells. Our results indicate that transformation of chicken embryo fibroblasts by Rous sarcoma virus results in the accumulation of RNA from approximately 1000 average-sized new transcription units. PMID- 6254078 TI - Segment-directed mutagenesis: construction in vitro of point mutations limited to a small predetermined region of a circular DNA molecule. AB - A general method for efficiently mutagenizing a predetermined segment of a closed circular duplex DNA molecule was used to construct mutations in two specific regions of the beta-lactamase (bla) gene carried by the small plasmid pBR322. The principle of segment-directed mutagenesis is the use of a single-stranded homologous DNA fragment to direct the nicking of circular duplex DNA within a segment defined by the DNA fragment in a two-step reaction. First, Escherichia coli recA protein is used to catalyze assimilation of the homologous single stranded DNA, producing a displacement loop ("D-loop") in the circular DNA. Second, a small amount of the single-strand-specific S1 nuclease is used to nick the displaced DNA. The segment-directed nicks are converted to small gaps, which are then mutagenized specifically with sodium bisulfite. A short (128-base pair) restriction endonuclease fragment from the center of the bla gene was used to direct mutagenesis with the result that 7.5% of the recovered plasmids were bla- mutants and 49/51 of these mutants, mapped genetically, were found to lie in a deletion interval whose endpoints approximate those of the restriction fragment. Similar results were obtained when another short fragment covering the beginning of the gene was used; many of these mutations map in the region coding the "signal" sequence thought to be involved in secretion of beta-lactamase. PMID- 6254079 TI - Four heat shock proteins of Drosophila melanogaster coded within a 12-kilobase region in chromosome subdivision 67B. AB - Unique coding sequences for four heat shock proteins of Drosophila melanogaster, hsp 28, hsp 26, hsp 23, and hsp 22, are clustered in a 12-kilobase interval at chromosome subdivision 67B. The four genes are not transcribed in the same direction and each gives rise to a separate messenger RNA, with no indication of intervening sequences. Including the present results, the genes for all seven major heat shock proteins of D. melanogaster are now cloned are found to exhibit a variety of patterns of organization at the five loci they occupy. PMID- 6254080 TI - Replication and expression of thymidine kinase and human globin genes microinjected into mouse fibroblasts. AB - A mixture of two recombinant plasmids was microinjected into mouse thymidine kinase-negative fibroblasts (L cells). One plasmid contained the thymidine kinase gene of herpes simplex virus type I and the other contained the human beta globin gene. Seven fibroblast colonies arising from injected cells incubated in hypoxanthine/aminopterin/thymidine medium were analyzed. These microinjected cells were shown to: (i) produce functionally active herpes simplex type I thymidine kinase enzyme, (ii) replicate the human beta globin gene, and (iii) produce human beta globin mRNA sequences at low levels. Thus, the genetic defect (lack of thymidine kinase activity) was corrected by the microinjected thymidine kinase gene, and a coinjected human beta globin gene was replicated and weakly expressed. PMID- 6254081 TI - Effect of diethyldithiocarbamate rescue on tumor response to cis-platinum in a rat model. AB - The nephrotoxic effects of cis-dichlorodiamineplatinum(II) (NSC-119875) (DDP) in female F344 rats were effectively inhibited by administration of sodium diethyldithiocarbamate (DDTC) in doses of 750 mg/kg intraperitoneally or 100 mg/kg intravenously 2 hr after administration of DDP. Rats were inoculated with mammary tumor 13762 and treated after 10 days with DDP (2.0 or 8.0 mg/kg) with or without DDTC rescue (750 mg/kg intraperitoneally or 100 mg/kg intravenously). Initial reductions in tumor size were identical with or without rescue in all experiments. High-dose intraperitoneal rescue, however, resulted in earlier relapse and more rapid progressions at both DDP doses than was observed in the absence of rescue. Low-dose intravenous rescue led to a tumor response identical to that observed without rescue. Urinary excretion of free DDTC was increased by prior administration of acetazolamide; however, this combination was more toxic to rats after DDP administration than was DDTC alone. Intravenous administration of DDTC appeared to be the most effective route for delivery of this ligand to the kidney. These results support our earlier mechanistic hypothesis and demonstrate the feasibility of inhibition of cis-platinum toxicity by DDTC without inhibition of the antitumor effect. PMID- 6254082 TI - Transfer of Epstein-Barr virus receptors to receptor-negative cells permits virus penetration and antigen expression. AB - Epstein-Barr virus (EBV) receptors were implanted into the membranes of receptor negative cells, using Sendai virus envelopes as vehicles. The presence of the receptors in the target cell membrane was demonstrated by monitoring the fate of radioiodinated donor membranes. Receptors could be detected for at least 36 hr after implantation. [3H]Thymidine-labeled EBV bound efficiently to receptor implanted cells but not to control cells. Binding was inhibited by an excess of nonlabeled virus. Of the [3H]thymidine-labeled EBV DNA, 50-75% was found inside the receptor-implanted, EBV-exposed cells 24 hr after the infection. The viral genome was functionally active in B lymphocyte-derived cell lines of human, murine, and baboon origin; in T lymphocyte-derived lines of human and murine origin; in mouse fibroblasts; and in freshly explanted mouse lymphocytes, as shown by the expression of EBV-determined nuclear, early, and viral capsid antigens. PMID- 6254083 TI - Low density lipoprotein receptor activity in human monocyte-derived macrophages and its relation to atheromatous lesions. AB - Human peripheral monocytes, isolated from a previously unused source (a leukocyte concentrate byproduct of the plateletphoresis procedure for platelet transfusion), transformed into macrophages while cultured with 5% human serum or isolated lipoprotein fractions. Used for the study of their cholesterol (Chol) metabolism, these human monocyte-derived macrophages had a high-affinity receptor that is saturable, specific for low density lipoprotein (LDL) and maximally induced by incubation for as little as 24 hr in medium devoid of lipoproteins or Chol. Macrophages were shown to have separate receptor activity for 125I-labeled LDL and 125I-labeled acetylated LDL; macrophages that had been incubated with lipoprotein-depleted serum degraded native and acetylated LDL at similar rates. The receptor for LDL was functional in maintaining Chol homeostasis, as demonstrated by feedback inhibition of Chol synthesis after culture with LDL or very low density lipoprotein (VLDL). The Chol content of macrophages was doubled by incubation with medium containing VLDL compared to incubation with LDL (60 microgram of Chol per ml of medium). Incubation with native lipoproteins did not lead to accumulation of esterified Chol by macrophages. Changes in the Chol metabolism of macrophages, rather than modifications in circulating LDL, may cause these cells to store cholesteryl ester and take on the characteristics of cholesteryl ester-laden macrophages of atheromatous lesions. PMID- 6254084 TI - Generation of an electrochemical proton gradient in Streptococcus cremoris by lactate efflux. AB - Recently an energy-recycling model was proposed that postulates the generation of an electrochemical gradient in fermentative bacteria by carrier-mediated excretion of metabolic end products in symport with protons. In this paper experimental support for this model is given. In batch cultures of Streptococcus cremoris with glucose as the sole energy source the maximal specific growth rate decreased by 30% when the external lactate concentration was decreased from 50 to 90 mM. In the same range of external lactate concentrations the molar growth yield Y for glucose as measured in energy-limited chemostat cultures also showed a 30% drop. From Y max lactose values of S. cremoris grown in the presence and absence of added lactate it was calculated that the net energy gain from the lactate efflux system was at least 12%. Lactate efflux from de-energized cells loaded with lactate could drive the uptake of leucine. This uptake was sensitive to carbonylcyanide p-trifluoromethoxyphenylhydrazone and was only partly inhibited by dicyclohexylcarbodiimide (DCCD). The limited inhibition by DCCD of lactate-induced leucine uptake indicates that ATP hydrolysis was not the driving force for transport of leucine. Uptake studies with the lipophilic cation tetraphenylphosphonium demonstrated that lactate efflux increased the electrical potential across the membrane by 51 mV. The generation of an electrical potential by lactate efflux and the demonstration of a potassium efflux-induced uptake of lactate indicates that lactate is translocated across the membrane by a symport system with more than one proton. PMID- 6254086 TI - Peptide inhibitor of morphine- and beta-endorphin-induced analgesia. AB - The synthetic beta-endorphin analogs with the omission of the NH2-terminal [Met]enkephalin segment [beta-endorphin-(6-31) and beta-endorphin-(20-31)] are shown to inhibit morphine- or beta-endorphin-induced analgesia in mice by the tail-flick test, whereas the synthetic NH2-terminal pentadecapeptide beta endorphin-(1-15) has no inhibitory activity. This study raises the possibility that endogenous inhibiting peptides exist in the brain which play a role in the regulation of endorphin actions. PMID- 6254085 TI - Expression of cloned hepatitis B virus DNA in human cell cultures. AB - DNA was isolated from the ayw subtype of hepatitis B virus (HBV) that had been incubated in vitro with all four deoxynucleoside triphosphates in order to complete the circular viral genome by means of the endogenous DNA polymerase. The purified viral DNA was cleaved with EcoRI restriction endonuclease, inserted into the EcoRI site of plasmid pBR322, and cloned in Escherichia coli chi 1776. DNA from a clone, pHBV-1, that contained a 3200-base-pair insert of HBV DNA was cleaved with EcoRI and incubated with phage T4 ligase under conditions favoring intramolecular ligation. HeLa cell cultures exposed to this DNA showed marked cytopathic changes, accompanied by production of hepatitis B core and surface antigens, 11-14 days after subculture. Electron microscopic examination of anti hepatitis B surface antigen immunoprecipitates from culture media of these cells revealed both 42-nm particles with central cores and 20-nm round particles. Although neither intact circular nor EcoRI-cleaved linear pHBV-1 DNAs evoked these effects in HeLa cells, both cytopathic changes and intranuclear hepatitis B core antigen were detected in HeLa cells infected with Dane particles. PMID- 6254087 TI - Morphine and opioid peptides reduce paraventricular neuronal activity: studies on the rat hypothalamic slice preparation. AB - Extracellular discharges of neurons in the paraventricular nucleus (PVN) were recorded from slices of rat hypothalamus in vitro. PVN neurons (n = 14) were identified by the criteria of (i) phasic activity patterns and (ii) antidromic invasion from the neurohypophysial tract. Neurons not displaying either of these features were considered unidentified with respect to physiological function (n = 85). The majority of unidentified neurons responded to bath application of morphine (1 microM), [D-Ala2,Met5]enkephalin (1 microM) or beta-endorphin (0.01-1 microM) with a prompt, reversible, dose-related reduction in spike discharge frequency. Naloxone (1 microM) antagonized the opioid-induced depressions in some, but not all, cases. At the concentrations tested, no tachyphylaxis to the effects of the opioids was observed. The opioid effects on putative neurohypophysial neurons were less pronounced; while 2 were depressed, the remaining 12 displayed no change in frequency or pattern of discharge to micromolar concentrations of morphine, [D-Ala2,Met5]enkephalin, or beta endorphin. Our results indicate that opioids depress neuronal activity in the rat PVN via an interaction with a specific opiate receptor but that this effect is more pronounced on unidentified neurons than on putative neurohypophysial neurons in the slice. PMID- 6254088 TI - In vitro autoradiography of opiate receptors in rat brain suggests loci of "opiatergic" pathways. AB - Slide-mounted sections of unfixed frozen rat brain can be labeled in vitro with [3H]naloxone to show the mu-like ligand selectivity characterized in previous studies. We have developed an autoradiographic technique using hot paraformaldehyde vapors to prevent diffusion of ligands with reversible binding. Resolution at the light level is sufficient to detect concordance between receptor patterns and terminal fields of axonal projections marked by tract tracing techniques. The opiate receptor distribution suggests the existence of widespread intrinsic and several longer multisynaptic "opiatergic pathways within sensory and limbic circuits. One multisynaptic pathway may link olfactory structures with limbic circuits in the amygdala and habenula. Another may lie in limbic cortical structures. Opiate receptors are numerous also in sensory systems, and within primary sensory nuclei (visual, auditory, olfactory, somatic) they are found superficially in laminated structures. Together, the opiate receptors are well placed to control incoming sensory and subsequent limbic information processing. PMID- 6254089 TI - Localization of cyclic GMP-dependent protein kinase and substrate in mammalian cerebellum. AB - The regional and cellular distribution of guanosine 3',5'-cyclic monophosphate (cGMP)-dependent protein kinase (ATP:protein phosphotransferase,EC 2.7.1.37) in mammalian brain was examined by use of the photoaffinity label 8-azidoinosine 3',5'-cyclic monophosphate. Of the regions examined, cerebellum had by far the highest concentration of this enzyme. The cellular localization of cGMP-dependent protein kinase within the cerebellum was determined by examination of mutant mice missing specific types of cerebellar neurons. Mutant mice lacking Purkinje cells had greatly reduced amounts of cGMP-dependent protein kinase, whereas the loss of another cell type, granule cells, did not reduce cGMP-dependent protein kinase levels. By using the same strains of mutant mice, a 23,000-dalton soluble cerebellar substrate for cGMP-dependent protein kinase was also shown to be enriched in Purkinje cells. In contrast, the concentration of type I 3',5'-cyclic AMP-dependent protein kinase in the cerebellum was unaffected by the absence of Purkinje cells and only slightly reduced by the absence of granule cells. The enrichment in Purkinje cells of the cGMP-dependent protein kinase and its substrate suggests an important role for cGMP and cGMP-dependent protein phosphorylation in the function of this type of neuronal cell. PMID- 6254090 TI - Adenosine receptors in brain membranes: binding of N6-cyclohexyl[3H]adenosine and 1,3-diethyl-8-[3H]phenylxanthine. AB - N6-Cyclohexyl[3H]adenosine ([3H]CHA) and 1,3-diethyl-8-[3H]phenylxanthine ([3H]DPX) to bind to adenosine receptors in brain membranes. The agonist [3H]CHA has high affinity in both bovine and guinea pig brain (Kd, 0.7 nM and 6 nM, respectively). [3H]CHA binding kinetics are slow (dissociation t1/2;60 min); binding is much higher at 25 degrees C than at 0 degrees C and is inhibited by guanine nucleotides. Potencies of nucleosides and xanthines in competing for [3H]CHA sites indicate that specific binding is entirely to A1 adenosine receptors. In bovine brain, the antagonist [3H]DPX exhibits high-affinity binding (Kd, 5 nM) to the same A1 receptors that bind [3H]CHA. Binding kinetics are rapid (dissociation t1/2, 1 min), and binding is moderately higher at 0 degrees C than at 25 degrees C. In guinea pig brain, [3H]DPX binding has only moderate affintiy (Kd 50 nM), and about 60% of specific binding is to sites that resemble A2 adenosine receptors. PMID- 6254092 TI - Using profiles of saccharin and water drinking to detect and discriminate actions of drugs and toxicants. AB - Experiments were conducted to investigate the feasibility of using the pattern of saccharin and water drinking to detect acute and chronic administration of drugs and toxicants. Procedural variables were found to be crucial. When rats were naive for the saccharin drinking fluid, a single injection of LiCl or 2 deoxyglucose produced persistant saccharin aversion. Hypertonic saline produced only a transient saccharin aversion. If rats were pre-exposed to saccharin, the 2 deoxyglucose injection and hypertonic NaCl produced an increase in saccharin drinking but LiCl was without effect. Several types of chronic treatment were given to saccharin-experienced rats. Chronic 2-deoxyglucose, LiCl, and Pb administration produced gradually developing saccharin aversion and qualitatively different patterns of saccharin and water drinking. Chronic administration of hypertonic NaCl or insulin or chronic food deprivation had no impact on saccharin preference. It was concluded that patterns of saccharin and water drinking can be used to detect the administration of a drug or toxicant and perhaps even the time course of action, but may not detect a substance given previous to saccharin, perhaps because the animal cannot associate these now familiar perturbations with the novel saccharin solution. This means that existing toxic states may not be detected by using saccharin preference as a probe. PMID- 6254091 TI - Similar luteinizing hormone-releasing hormone binding sites in rat anterior pituitary and ovary. AB - To study the luteinizing hormone-releasing hormone (LH-RH; luliberin) receptors in the rat anterior pituitary gland and ovary, 125I-labeled [D-Ser(TBU)6des-Gly NH2(10)]LH-RH ethylamide was used as a labeled ligand. The binding characteristics were assessed by Scatchard analysis of labeled ligand binding and by potency displacement with unlabeled peptides. Similar Kd values, ranging from 0.1 to 0.3 nM, were found for the labeled and unlabeled peptides in both tissues. A similar order of potency was observed between the finding affinity of 15 peptides in anterior pituitary and ovarian homogenates and their biological activity on luteinizing hormone release in rat anterior pituitary cells in culture. These data demonstrate that the LH-RH receptors present in the rat ovary have a specificity similar to that of the anterior pituitary LH-RH receptor controlling secretion of luteinizing hormone and follicle-stimulating hormone. Moreover, the binding affinities of the LH-RH agonists and antagonists can account, at least up to a large extent, for their relative biological potencies. Although there definitely are specific LH-RH receptors in the ovary which may play a role in the antifertility effects observed after administration of LH-RH agonists, the possible physiological significance of these ovarian receptors is still unknown and of great biological interest. PMID- 6254093 TI - Synthesis of pelargonoyl-cyclic decapeptide analog of the antibiotic polymyxin B.1. AB - The synthesis of pelargonoyl-cyclic decapeptide, analog of polymycin B1, is described. The open-chain protected decapeptide was synthesized on a polymer support, starting with threonine as the C-terminal amino acid residue, and was cleaved satisfactorily by hydrazinolysis. The alpha-amino protecting Boc-group was removed with HCl (1 mol/l) acetic acid and the resulting decapeptide hydrazide was converted to the azide with nitrous acid. Cyclization of the azide in pyridine at peptide concentration 2.5.10(-5) mol/l gave the penta benzyloxycarbonyl-substituted decapeptide in 65% yield. Catalytic hydrogenation afforded the pelargonoyl cyclic decapeptide pentahydrochloride (6) in 75% yield. The synthetic product (6) exhibited an activity comparable to that of the natural polymyxin B1 against Bacillus subtilis and Staphylococcus aureus, whereas it showed only 2% of the activity to Escherichia coli2. PMID- 6254094 TI - Tricyclic antidepressant drug interactions with histamine and alpha-adrenergic receptors. AB - Tricyclic antidepressant drugs are remarkable in their therapeutic actions. When given acutely they are generally sedating. Then after a lag of 1-3 weeks, they alleviate depressive symptoms. Besides the delayed psychic energizing properties, the immediate apparent sedative actions may have importance for the relief of psychomotor agitation. This article describes influences of the drugs on histamine H1 and alpha-adrenergic receptors which may be of relevance to the energizing effects and relief of psychomotor agitation. PMID- 6254095 TI - The wavelength dependence of Herpes simplex virus inactivation by ultraviolet radiation. PMID- 6254096 TI - Ultraviolet enhanced reactivation of Herpes simplex virus inactivated by different wavelengths of UV radiation. PMID- 6254097 TI - On the state of chromophore protonation in rhodopsin: implication for primary photochemistry in visual pigments. PMID- 6254099 TI - Purification of phytase from rat intestinal mucosa. AB - Phytase has been purified from intestinal mucosa of rats fed on a phytic acid enriched diet. The purification consisted of four steps: homogenate preparation, ultrafiltration procedure, DEAE cellulose chromatography, and Sephadex G-100 chromatography. The enzyme was purified 828-fold, as can be seen from the polyacrylamide gel electrophoresis pattern. PMID- 6254100 TI - An improved viscosimetric assay for vertebrate collagenase activity. AB - An improved viscosimetric assay for vertebrate collagenase acitivity is described. The assay is carried out at 35 degrees C in the presence of 1 M glucose to prevent fibril formation. The decrease in viscosity is linear with ime and proportional to enzyme concentration. PMID- 6254098 TI - Interaction of sulfur-containing radioprotectors with DNA: a spectrophotometric study. AB - The interaction between sodium-compensated DNA and several aminothiol radioprotectors [cysteamine; methyl-2-cysteamine; cysteamine phosphorothioate; N (2-mercaptoethyl) 1,2-diaminoethane; N-(2-mercaptoethyl)-1,3-diaminopropane; N-(3 aminopropyl)-2-aminoethyl phosphorothioic acid] has been studied by spectrophotometry. In all cases, elevation of the melting point (Tm) of the DNA radioprotector complex was observed. The interaction of these ionized aminothiols with phosphate groups of DNA is essentially an electrostatic one, like that for metallic cations, and can be expressed by the Schildkraut-Lifson equation Tm = a log Cradio + b, where a and b are adjustable parameters and Cradio is the concentration of the radioprotectors. PMID- 6254101 TI - Electron spin resonance spin-label studies of mouse olfactory epithelium. AB - Three classes of interaction of spin-labeled odors with olfactory membrane of mouse were identified by electron spin resonance spectroscopy and correlated with the olfactory potencies of those odors. Also, variation of fluidity in this membrane was probed using spin-labeled lipids in which the nitroxide group was at increasing distances from the lipid headgroup. A cooperative model of olfactory transduction in agreement with the results is introduced, and typical dose response curves are computed that can predict molecular features necessary for a strong odor. PMID- 6254102 TI - The living state and cancer. AB - Most inanimate systems are build of closed-shell molecules in which electrons lack excitability and mobility. These electrons can be rendered reactive and mobile by taking out some of them, desaturating the system electronically. Single electrons can be taken out of molecules by transfer to an external acceptor, creating two radicals that form a biradical having no net charge. The living state is such an electronically desaturated state. The universal electron acceptor of the biosphere is oxygen. Before light and O2 appeared, a weak electron acceptor could occur through linkage of two C=O groups to glyoxal and addition of a methyl group. The resulting methylglyoxal, being a weak acceptor, could lead to only a low degree of desaturation and thus to formation of only the simple life forms extant during this dark and anaerobic period--the alpha period. During the subsequent aerobic beta period, more highly differentiated life forms could develop because of occurrence of O2, a strong electron acceptor leading to a greater degree of desaturation. When dividing, however, beta-type cells return partially to the proliferative alpha state. The process of electron (charge) transfer, described here in two models, depends on the dielectric constant of the medium and the relative concentration of SH and methylglyoxal. Structure-building proteins that perform the main biological functions carry with them this chemical mechanism of their desaturation. Central to the mechanism is the NH2 of lysine that attaches a methylglyoxal. Through folding of the side chain, the CO groups of resulting Schiff bases can come in touch with the NH's of the peptide chain and accept electrons from it, desaturating it. Ascorbic acid is the catalyst of this charge transfer, which brings protein into the living state. Purified protein is inanimate matter. Manganese and oxygen form part of the chemical mechanism of desaturation, and the charge transfer reactions studied were found to be autocatalytic. It follows from the above observations that a cancer cell is a cell trapped in the alpha state. PMID- 6254103 TI - Effects of cryptand 2.2.1Py on the fast sodium current in cardiac Purkinje fibers. AB - For study of dose-dependent influence on sodium current, sheep heart Purkinje fibers were perfused with a cryptand (2.2.1Py) and measured for resting potential, overshoot, amplitude and duration of action potential, refractory period, and rate of rise. Concomitant investigation was made by voltage clamp. The cryptand was found to depress maximal rate rise with increase of concentration and induce shift toward negative potential with increase of dose. Also, effect on sodium current kinetics was observed but not on resting potential. The findings indicate that 2.2.1Py action probably is not primarily ionophores, negating the idea that cryptands promote transmembrane ion exchange. PMID- 6254104 TI - Entropy correlations with ethanol-induced changes in specified patterns of nerve impulses: evidence for 'byte' processing in the nervous system. PMID- 6254106 TI - Homicide among black males. Highlights of the symposium sponsored by the Alcohol, Drug Abuse, and Mental Health Administration, Washington, D.C., May 13--14, 1980. PMID- 6254105 TI - Beta-endorphin causes retrograde amnesia and is released from the rat brain by various forms of training and stimulation. AB - The endogenous opiate peptide, beta-endorphin (0.4, 1.0, 2.0, and 10.0 microgram/kg) was injected IP into rats immediately after training in a shuttle avoidance task, and its effect on memory retention was evaluated in test sessions carried out 24 h later. The drug was found to cause retrograde amnesia, the ED50 being 1.0 microgram/kg. Beta-endorphin immunoreactivity was measured in the hypothalamus and rest of the brain of rats submitted to training, or test sessions of shuttle avoidance learning, pseudoconditioning in the shuttle-box, tones alone, or foot-shocks alone. After training in any of the four paradigms, there was a marked (46-60%) depletion of beta-endorphin immunoreactivity in the rest of the brain. No changes were detected in the hypothalamus or after test sessions. The loss of beta-endorphin immunoreactivity may be attributed to release of this substance caused by the stimuli used for training. From the present findings, as well as previous observations on the memory-facilitating influence of the opiate receptor antagonist, naloxone, it is concluded that there is a physiological amnesic mechanism mediated by beta-endorphin (and perhaps other opoid peptides as well), which is triggered by the non-associative factors present in the various forms of learning. PMID- 6254107 TI - Advocacy for life: mandates, models, and priorities for prevention. PMID- 6254108 TI - Treatment of acromegaly by transethmoidal hypophysectomy. AB - The results of transethmoidal hypophysectomy are recorded in 34 patients with acromegaly. The post-operative growth hormone (GH) level was reduced to normal in 27 (80 per cent) and to less than 18 mu/l in 33 of the 34 cases. Two patients failed to respond clinically though in one of these the serum GH fell from 100 to 14 mu/l. Both the failures had had previous surgical interference. Amongst the responders there have been no recurrences. In view of these results we are of the opinion that transethmoidal hypophysectomy is at present the treatment of choice for acromegaly. PMID- 6254109 TI - The effects of viral infections on renal transplants and their recipients. AB - A prospective study of viral infections occurring after 188 renal transplants in 167 patients showed active cytomegalovirus (CMV) infection after 52 per cent of transplantations. All 37 CMV seronegative cases who received grafts from seronegative donors remained free of infection, while 24 (70.6 per cent) of 34 seronegative recipients whose donors were seropositive developed primary CMV infection (p less than 0.001). The diagnosis of 92 per cent of these primary infections was made between one and two months after grafting. Secondary CMV infection was found in 71 (62 per cent) of 114 seropositive cases, and the frequency of infection was not affected by the CMV status of the renal donor. Neither acute rejection episodes nor total graft rejections were associated with primary or secondary infections. CMV was isolated from a colonic abscess and the relationship of the virus to the intestinal disease is discussed. Herpes simplex virus was isolated from 47 per cent of cases and 32 per cent had an increase in antibody titre. Zoster was seen in nine patients, representing an incidence of 3.4 per cent per year. Other viral or mycoplasmal infections diagnosed included 71 due to respiratory tract pathogens, and a single case of hepatitis B. None of these infections was particularly severe or frequent and no association with graft rejection was detected. PMID- 6254110 TI - Ultrasound of the whole breast utilizing a dedicated automated breast scanner. AB - Innovations in design of a dedicated breast scanner resulted in automation of the scanning process, the production of high resolution images of the whole breast and an efficient mode of image review. The results of clinical evaluation of the prototype of this breast scanner investigating normal breasts as well as benign and malignant breast lesions are presented. PMID- 6254111 TI - Ultrasound visualization of the breast in symptomatic patients. AB - More than 400 breast patients (primarily symptomatic) have been examined with ultrasound alone and in combination with low-dose mammography. Symptomatic pregnant women and young patients with palpable masses were examined with ultrasound alone. In young, dense breasts, ultrasound was found to surpass mammography in the differential diagnosis of both cystic and solid masses. In older patients, the tumor characteristics displayed on ultrasound augmented those of mammography, resulting in increased diagnostic accuracy. PMID- 6254112 TI - [Abrikosov's myoblastoma]. PMID- 6254113 TI - [Salmonella isolated from city sewage for agricultural use]. PMID- 6254114 TI - [Chemodectoma of the larynx]. PMID- 6254115 TI - [Value of contrastography as a diagnostic means in paranasal sinus diseases]. AB - The authors report on their investigations in contrast phase radiography of the paranasal sinuses, insisting to a greater extent on the data furnished by lipoiodine used as a contrast medium than on the technical aspects. A description is given of the views with a therapeutical indication, but also of the possible diagnostic errors. Particular attention is drawn to the advisability of introducing in current practice the displacement method used for contrast phase radiography of the posterior sinuses, showing their diagnostic and therapeutical advantages. PMID- 6254116 TI - [Clinical and evolutive considerations on rhinosinus cylindromas]. AB - With reference to 7 cases of rhinosinusal cylindroma, rarely, encountered at this level (approximately 3% of all malignant rhinosinusal tumours), the authors discuss the evolution of the tumour and its treatment in the light of recent published data and their own experience in cases followed up over a long interval. In contrast to the pathohistologic aspect according to which these tumours are relatively benign, cylindromas appear to be malignant tumours with a slow, infiltrative evolution and a marked tendency to recurrence. After many years they may be transformed into carcinomas. They seldom give metastasis to the regional lymph nodes, but often generalize in the end stage by haematogenic route (with localizations in the lungs, pleura, brain, spinal column, ribs, long bones). As they are radioresistant, initial broad surgical excision is compulsory followed--when surgery is performed in the advanced stages--by complementary radiotherapy (intracavitary cobalt, intracavitary contact roentgentherapy, telecobalt, teleradiumtherapy, electron therapy). PMID- 6254117 TI - [Wilms' tumor with intravascular growth to the right atrium]. PMID- 6254118 TI - Possible mechanism of stimulation of gastrin secretion by exogenous serotonin in rats. AB - The effect of 6-hydroxydopamine, propranolol, phentolamine, alpha-methyl-tyrosine and alpha-methyl-tyrosine plus propranolol on serotonin-stimulated gastrin secretion in rats has been examined. Gastrin secretion in response to administration of serotonin alone (10 mg/kg i.p.) was significantly reduced in rats pretreated with 6-hydroxydopamine or with propranolol. These results suggest that the effect of exogenous serotonin on gastrin secretion can be described as sympathomimetic and indirect. The serotonin-stimulated gastrin secretion was significantly enhanced by previous administration of phentolamine. Pretreatment with alpha-methyl-tyrosine also elevated serotonin-stimulated gastrin secretion, indicating that in the presence of diminished concentrations of the catecholamines, the influence of exogenous serotonin on secretion by G cells is increased. This enhancement in the serum gastrin levels was also reduced to a significant extent by simultaneous administration of propranolol, which suggested the activation of G-cell beta-adrenergic receptors after serotonin administration. PMID- 6254120 TI - Hepatic insensitivity to glucagon in ob/ob mice. AB - Hepatic cAMP concentration of normal mice increased 40 fold within 10 min after a single dose of glucagon (2 mg/kg, IP). In contrast, hepatic cAMP increased only 2 fold in ob/ob mice. Glucagon induced hepatic L-phenylalanine:pyruvate aminotransferase and stimulated glycogenolysis in normal mice but failed to elicit these cAMP-mediated responses in ob/ob mice. The insensitivity of ob/ob mice to glucagon was not ameliorated by fasting or by theophylline. PMID- 6254119 TI - N-Oxide reduction by hemoglobin, cytochrome C and ferrous ions. AB - Indicine N-oxide is reduced to indicine by Fe(II) ions, by enzymatically reduced cytochrome c, and by ascorbic acid in conjunction with hemin or cytochrome c. Indicine N-oxide is not reduced by native hemoglobin, but is reduced by denatured hemoglobin. Oxygen competes with indicine N-oxide for reduction by denatured hemoglobin. PMID- 6254121 TI - The relationship of the cyclic nucleotide system to inhibition of hepatic drug metabolism in Walker 256 carcinoma-bearing rats. AB - The hepatic cyclic nucleotide system and hepatic monooxygenase activity were examined in male rats following intramuscular or subcutaneous Walker 256 carcinosarcoma transplantation. Twelve days of continuous s.c. tumor growth significantly increased hepatic cyclic AMP levels, while levels of cyclic GMP, cytochrome P-450, cytochrome b-5, and p-chloro-N-methylaniline metabolism were significantly decreased. Whole blood from 6 day i.m. tumor-bearing rats incubated with liver slices obtained from non-tumor-bearing rats produced significantly elevated hepatic cyclic AMP levels concurrent with significantly depressed hepatic p-chloro-N-methylaniline metabolism. The chronological monitoring of tumor growth demonstrated a close temporal relationship between decreased cyclic AMP-dependent protein kinase activity, microsomal metabolism of p-chloro-N methylaniline, and the mixed-function oxidase system. Significant changes in these hepatic enzyme systems occurred as early as 17 hours following tumor transplantation. At this same time, sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis revealed the appearance of a 184,000 molecular weight protein in hepatic tissue from all tumor-bearing rats. These studies are compatible with the proposal that the hepatic cyclic AMP system may modulate toxohormone effects on hepatic drug biotransformation. PMID- 6254123 TI - A neutral metallo-proteinase of human leucocytes: initial demonstration and characterization. PMID- 6254122 TI - Effects of carbonyl compounds (4-hydroxyalkenals) originating from the peroxidation of liver microsomal lipids on various microsomal enzyme activities of the liver. AB - Carbonyl compounds released during the NADPH-Fe dependent peroxidation of liver microsomal lipids and identified as 4-hydroxyalkenals (almost entirely as 4 hydroxynonenal) while inhibiting microsomal enzymes (such as glucose 6 phosphatase and aminopyrine demethylase) which are affected by lipid peroxidation, have no effect on microsomal NADPH-cytochrome c reductase. The latter enzyme activity is unaffected (or even increased) when liver microsomes are allowed to peroxidize in the NADPH-Fe dependent system. NADPH-cytochrome c reductase, contrary to the other enzymes, is similarly unaffected after CCl4 poisoning, that is in a situation in which peroxidation of membrane lipids of liver endoplasmic reticulum has been unequivocally demonstrated. It appears therefore that the effects exherted by lipid peroxidation or by 4-hydroxyalkenals originating from lipid peroxidation parallel the effects of CCl4 intoxication in vivo. PMID- 6254124 TI - [Rotavirus in infantile diarrhea (author's transl)]. PMID- 6254125 TI - [The pulmonary lymphoid system. Development and immunological implications]. PMID- 6254126 TI - [Significance of immunological investigation in pulmonary pathology]. AB - An extensive range of investigations were used in a comparative study of immune reactivity in the tuberculous pulmonary pathology, as well as in sarcoidosis, pneumonia and cancer of the lungs. T and B lymphocyte populations were followed, indexes of leucocyte migration, induced lymphoblastogenesis to phytohaemagglutinin, and the serum levels of immunoglobulins. Also the intensity of the hypersensitivity to tuberculin was investigated, to allergens extracted from staphylococcus and streptococcus strains, as well as against organ antigens (pulmonary tissues). Differences were evidenced, of immunologic reactivity in various nosologic entities investigated. The dynamic follow-up of some of the cases has demonstrated that the immunological reactivity varies in parallelly with severity of cases, deficiences being corrected by adequate therapy. The immunologic status may be considered a criterium for a rational pathogenetic treatment, for assessing the efficiency of such a treatment, as well as for the differential diagnosis of pulmonary diseases. PMID- 6254127 TI - [Late results of strictly supervised treatment of patients with newly detected pulmonary tuberculosis]. AB - The late results are analized, of a strictly supervised treatment of 160 patients with pulmonary tuberculosis, of the secondary bacilliferic type, recently discovered, between July 1974 and December 1976. The criterium for assessing the results was the bacteriologic examination. After the first year 144 of the patients became negative (90%), while 16 remained positive (10%). Prolonged treatment, up to 2--3 years also led to negativation of these causes, with the only exception of a single patient that did not cooperate, and who became chronically ill. After one-and-a-half year 2 patients again became positive, of which one died with fulminating hemophytysis, and the second one in cardio respiratory failure. Another 6 patients became positive after two years, while two other were positive at three years and one each after four, respectively five years. Two are still under treatment, while the remaining patients were all negative for at least two years. At the end of the observation period 155 of the initially 160 bacilliferic patients were considered as solved, and do not raise anti-epidemic problems. It is shown in conclusion that the modern anti tuberculous treatment can lead to recovery of the majority of patients. Those who are still bacille carriers, or who recidivate, can also be solved by continued treatment for a period of up to 2--3 years. The patients with multiple deficiencies have increased risks to develop relcidives, and they should be followed with perseverance for a long time. The recommended therapeutic regimens are not significantly different from the viewpoint of their efficiency, provided they are administered in a strictly supervised manner. The reactivity of the organism probably has an important role in the efficiency of the modern anti tuberculous treatment. PMID- 6254128 TI - [The late results of respiratory kinesitherapy in tubercular serofibrinous pleurisy]. AB - The authors have investigated 93 cases with sero-fibrinous pleurisy in their antecedents, and that had kinetotherapy during their disease. All the cases were controlled from the viewpoint of the respiratory function, as well as by radiological and electrocardiographic methods. Changes in the ventilatory function were evaluated by increased VEMS in absolute value in contrast with the VEMS value on hospitalization. The general late results of respiratory kinetotherapy were reflected in the fact that 84% of the cases presented either significant increase in the value of VEMS (56%), or had stationary values (28%). The most significant functional increases were noted in the patients who were under the age of 18 years upon release from hospital (median age : 14,8 years), and were mostly due to somatic development, and physical activity. The positive effects of physical activity in the frame of the occupation of the patients were amplified by respiratory kinetotherapy continued at home. Respiratory kinetotherapy demonstrated its efficiency especially in the subjects from lowage groups, and males had better results than females. Advanced age, important pleural sequels, as well as other disturbances, without apparent relation to the pleurisy, had negative effects. In the present conditions of treatment (chemotherapy + corticoid therapy and immediate and long-duration kinetotherapy) sero-fibrinous pleurisy has no significant impact on the socio-professional evolution of the patient. PMID- 6254129 TI - [Study of the ocular toxicity of ethambutol]. AB - Thirty cases were studied, of children aged between 4 and 5 years, with latent or manifest (overt) pulmonary tuberculosis under treatment with etambutol (EMB) administered intermittently (2/7) in amounts of 25 mg. per kg of body weight. Ophtalmological investigations consisted in evaluation of the visual acuity, of the visual field, of the chromatic sense, pupillary reflexes and an examination of the fundus. These were performed before the start of the treatment, then at 3 and 6 months after the treatment was begun. No cases of toxic ocular manifestations was recorded. The results are discussed on the basis of data from the literature, and care is recommended in the administration of etambutol. PMID- 6254130 TI - [Frequency of chronic bronchitis in an intensely polluted urban zone. Preliminary results in children. Analysis of the implicated factors]. AB - The starting point is that environment factors induce chronic bronchitis in adults and children and that the disease in adult is a consequence of respiratory tree susceptibility which might be better evidenced during childhood. The authors have studied a group of children aged 0--14 years in a highly air-poluted workers' quarter in the city of Baia-Mare. The frequence of chronic bronchitis was 10.3% with higher values in children below 5 years and over 10 years, the age group 5--9 years being a group with higher resistance to this disease. The figures are three times higher in boys than in girls, on possible endogenous factors. The girls could be, however, more subjected to "passive smoking" because of smokers presence in family and in bed room. The number of children in a family did not correlate with chronic bronchitis frequence. This frequence was significantly influenced by allergic and ear-nose-throat phenomena in the history, more evidently in 0--4 years and 10-14 years groups of age. These elements could be thus considered as risk factors. They also indicate the place to be acted upon in order to prevent chronic bronchitis in children. PMID- 6254131 TI - [Cartography in the "Universal Transverse Mercator" system (Gauss-Kruger projection) of sources shedding M. tuberculosis]. AB - The authors made use of maps prepared in the projection system known as the "Universal Transverse Mercator" (Gauss-Kruger projection) for the study of an epidemiometric indicator in tuberculosis, namely the instantaneous prevalence of bacili carriers on December 31 1978 in the Ilfov District. The representation allows to evaluate the density of sources of infection, and as a consequence, of areas in which antiepidemic measured have to be intensified. The extension of the study to other districts could provide data for assessing the epidemiologic potential in various territories, as well as comparisons and the dynamics of the potential. The method could also be used in the study of other epidemiometric indicators. PMID- 6254132 TI - [Idiopathic pulmonary hemosiderosis (case report)]. AB - A case is presented, of idiopathic pulmonary hemosiderosis in a female aged 19 years. The clinical onset occurred at the age of 3 years and the evolution was characterized by subfever, dispnoea, coughing and cyanosis. Radiological examination revealed reticulation and uniform distribution of nodules in both lungs. Other laboratory investigations have revealed hypochromic anaemia, restrictive syndrome and reduction of the maximal ventilation rate with marked arterial hypoxemia. Pulmonary bioptic puncture was performed and the patient died three days after puncture. Histopathologic examination of the bioptic sample and of necroptic specimens revealed fibrotic interstitial nodules filled with siderophages. The small and the median arteries displayed fragmentation of the elastic fibers, and hyperelastosis. The changes oberved allowed to make an exact diagnosis of idiopathic pulmonary hemosiderosis. PMID- 6254133 TI - [Results of bacteriological examinations in lymph-node and osteoarticular tuberculosis]. PMID- 6254134 TI - [Hepatitis B virus surface antigen (HBSAG) and primary liver carcinoma: a retrospective study]. PMID- 6254135 TI - [Determination of protein-bound iodine content in experimental Ferbam 76 poisoning]. PMID- 6254136 TI - [Polypeptide hormones and chronic renal insufficiency]. PMID- 6254137 TI - Maternal transmission of hepatitis B surface antigen in patients with hepatocellular carcinoma in Taiwan. AB - To determine the source of the highly prevalent hepatitis B virus (HBV) infection in our patients with hepatocellular carcinoma (HCC), we examined hepatitis B surface antigen (HBsAg) and its subtypes and antibody in 11 patients with HCC and their parents. All the patients were positive for HBsAg. Eight (73%) of the mothers were also HBsAg-positive, whereas only one of the seven fathers was an HBsAg carrier (P = 0.025). The observation is compatible with maternal transmission as a source of HBV infection in most of our patients with HCC. The subtype was identifiable in 10 patients, 9 with HBsAg/adw and one with adr. The subtype was identical in the patient--mother carrier pairs, suggesting that HBV infection in the patient and the mother is intimately related. This is further evidenced by the observation of a relatively uncommon adr subtype in one patient- mother pair. These observations suggest that the HBV infection in our patients results from vertical transmission from their carrier mothers probably long before the development of HCC. PMID- 6254138 TI - An epidemic of rotavirus-associated gastroenteritis in a nursing home for the elderly. AB - 92 cases of acute gastroenteritis were registered among 256 individuals during an outbreak in a nursing home for the elderly, the majority of patients being between 70 and 90 years of age. Most cases appeared in 4 of the 8 wards; 66% of the inmates of these wards became ill. Characteristic symptoms were initial nausea and vomiting followed by diarrhoea and low fever. A number of patients were severely ill. One patient died. Rotavirus infection was diagnosed by virus detection and/or antibody titre rise during the acute phase of the illness in 13 of 16 patients examined. At the end of the outbreak, high titres of complement fixing antibodies against rotavirus (greater than or equal to 64) were detected in serum from 21/22 patients convalescing from the disease, as compared to only 5/45 individuals with no signs of disease. It is tentatively suggested that the outbreak became extensive and rather severe because of lowered immunity against rotavirus infection among the elderly. PMID- 6254139 TI - Acute non-A, non-B hepatitis--clinical, epidemiological and histological characteristics. AB - Among 73 consecutive patients with biopsy documented acute non-toxic hepatitis, half of the patients (49%) had acute type B hepatitis, while 27 patients (37%) had acute type A infection. One patient had a significant rise in antibodies against cytomegalovirus. The remaining 10 patients (14%) fulfilled the criteria of hepatitis type non-A, non-B. The main type of exposure for hepatitis A was visit to endemic hepatitis areas (41%), and for type B it was drug addiction (46%). Half of the patients with hepatitis non-A, non-B had no known hepatitis exposure while some had visited endemic hepatitis areas or were drug addicts. The patients with non-A, non-B hepatitis had significantly less biochemical changes as compared to the patients with hepatitis B. In contrast, the histological findings showed the greatest activity in the biopsies from patients with hepatitis B and non-A, non-B. Follow-up liver biopsies in half of the patients with non-A, non-B hepatitis showed no signs of chronic active liver disease. It is concluded that hepatitis type non-A, non-B is a significant problem in Denmark. PMID- 6254140 TI - [Function of hormone receptors in disease]. PMID- 6254141 TI - [Function of LH releasing hormone outside the pituitary gland]. PMID- 6254142 TI - Early two-dimensional reconstruction and recent topics stemming from it. PMID- 6254143 TI - Catecholamine-induced alteration in sedimentation behavior of membrane bound beta adrenergic receptors. AB - Incubation of astrocytoma cells with catecholamines results in a decrease in catecholamine-stimulated adenylate cyclase activity and a concomitant alteration in the sedimentation properties of particulate beta-adrenergic receptors. The altered receptors exhibit agonist binding properties similar to those of receptors that are "uncoupled" from adenylate cyclase. PMID- 6254144 TI - DNA methylation and gene function. AB - In most higher organisms, DNA is modified after synthesis by the enzymatic conversion of many cytosine residues to 5-methylcytosine. For several years, control of gene activity by DNA methylation has been recognized as a logically attractive possibility, but experimental support has proved elusive. However, there is now reason to believe, from recent studies, that DNA methylation is a key element in the hierarchy of control mechanisms that govern vertebrate gene function and differentiation. PMID- 6254146 TI - Hepatitis B vaccine passes first major test. PMID- 6254145 TI - Environmental influences on serotonin and cyclic nucleotides in rat cerebral cortex. AB - The response to different environmental conditions and negative air ions was investigated on cerebral cortical serotonin and cyclic nucleotides. The results indicated that negative air ions alter the weight of the cerebral cortex and that concentrations of serotonin and cyclic nucleotides can be altered both by different environments and by negative air ions. The data stress the importance of the role of the environment when studying the structure and chemistry of the cerebral cortex. PMID- 6254147 TI - Visualization of specific angiotensin II binding sites in the brain by fluorescent microscopy. AB - The organum vasculosum of the lamina terminalis has been implicated as the site of receptors mediating central responses of angiotensin II. Up to now, this had been based on indirect evidence, but direct visualization of angiotensin II at its site of action has now been achieved by the use of a biologically active fluorescent angiotensin II agonist. The ventricular surface of the organum vasculosum lamina terminalis showed intense fluorescence, which was virtually eliminated by an excess of unlabeled angiotensin II. PMID- 6254148 TI - Electroconvulsive shock: progressive dopamine autoreceptor subsensitivity independent of repeated treatment. AB - Repeated electroconvulsive shock, applied to rats, induces a subsensitivity of dopamine autoreceptors located in the substantia nigra as indexed by single-unit electrophysiological techniques. This reduced sensitivity is time-dependent, since effects similar to those seen with repeated treatment were also observed when single electroconvulsive shock was followed by an appropriate treatment-free interval. These data, coupled with identical results after the repeated administration of tricyclic antidepressants, raise the possibility that a reduction of dopamine autoreceptor sensitivity could underlie both electroconvulsive shock and pharmacological treatment of depression. PMID- 6254149 TI - Latency of herpes simplex virus in absence of neutralizing antibody: model for reactivation. AB - Mice inoculated with herpes simplex virus (type 1) by the lip or corneal route and then passively immunized with rabbit antibody to herpes simplex virus developed a latent infection in the trigeminal ganglia within 96 hours. Neutralizing antibody to herpes simplex virus was cleared from the circulation and could not be detected in most of these mice after 2 months. Examination of ganglia from the antibody-negative mice revealed latent virus in over 90 percent of the animals, indicating that serum neutralizing antibody is not necessary to maintain the latent state. When the lips or corneas of these mice were traumatized, viral reactivation occurred in up to 90 percent of the mice, as demonstrated by the appearance of neutralizing antibody. This study provides a model for identifying factors that trigger viral reactivation. PMID- 6254150 TI - Anticonvulsants specific for petit mal antagonize epileptogenic effect of leucine enkephalin. AB - The anticonvulsants ethosuximide, sodium valproate, and trimethadione that are specific for petit mal epilepsy abolished in rats the electrical seizure activity and behavioral abnormalities produced by leucine enkephalin, whereas phenobarbital and phenytoin had no effect. The dose-response curve for naloxone against seizure activity induced by leucine enkephalin was the same as that in gamma-hydroxybutyrate-induced petit mal. These data indicate that the epileptic properties of leucine enkephalin are petit mal-like and raise the possibility of involvement of enkephalinergic systems in. The dose-response curve for naloxone against seizure activity induced by leucine enkephalin was the same as that in gamma-hydroxybutyrate-induced petit mal. These data indicate that the epileptic properties of leucine enkephalin are petit mal-like and raise the possibility of involvement of enkephalinergic systems in petit mal epilepsy. PMID- 6254151 TI - Prostaglandins, arachidonic acid, and inflammation. AB - The enzymatic oxidation of arachidonic acid has been shown to yield potent pathological agents by two major pathways. Those of the prostaglandin (PG) pathway, particularly PGE2, have been implicated as inflammatory mediators for many years. The discovery and biological activities of thromboxane A2 and prostacyclin as well as a destructive oxygen-centered radical as additional products of this biosynthetic pathway now require these to be considered as potential inflammatory mediators. Like PGE2, their biosynthesis is prevented by nonsteroidal anti-inflammatory agents. More recently, the alternative metabolic route, the lipoxygenase pathway, has been shown to yield a new class of arachidonic acid oxygenation products, called the leukotrienes, which also appear to be important inflammatory mediators. Unlike the prostaglandins, some of which play important roles as biological regulators, the actions of the lipoxygenase products appear to be exclusively of a pathological nature. PMID- 6254153 TI - Transformation by cloned Harvey murine sarcoma virus DNA: efficiency increased by long terminal repeat DNA. AB - The coding sequences for the transforming (src) protein (p21) of Harvey murine sarcoma virus have been localized to a 1.3 kilobase pair segment near the 5' end of the viral genome. Ligation of the viral terminal repeat DNA to the left end of the src region DNA markedly enhanced the low transforming efficiency of the src region DNA. PMID- 6254152 TI - Evidence for homologous actions of pro-opiocortin products. AB - alpha-Melanocyte-stimulating hormone (alpha-MSH), a modified fragment of adrenocorticotropic hormone, derives from the same biosynthetic route as beta endorphin and is stored by the same arcuate neurons. Microinjection of alpha melanocyte-stimulating hormone and several related peptides into the periaqueductal gray matter significantly reduced responsiveness to pain and had a behavioral profile similar to that produced by beta-endorphin. PMID- 6254155 TI - Glucose suppresses basal firing and haloperidol-induced increases in the firing rate of central dopaminergic neurons. AB - In the rat, doses of glucose sufficient to raise glucose concentrations in the blood to levels equivalent to those produced by a meal or stress suppress the firing of dopamine-containing neurons located within the substantia nigra. Glucose also prevents or reverses the increase in discharge rates of dopaminergic cells normally elicited by the antipsychotic agent haloperidol. PMID- 6254154 TI - Vasoactive intestinal peptide: a possible transmitter of nonadrenergic relaxation of guinea pig airways. AB - Vasoactive intestinal peptide, a smooth-muscle relaxant neuropeptide with neurotransmitter properties, was relaxed during electrical field stimulation of guinea pig trachea. The amount released correlated with the degree of relaxation, and the release was blocked by tetrodotoxin. Prior incubation of the trachea with antiserum to vasoactive intestinal peptide reduced the relaxation. Thus vasoactive intestinal peptide may mediate the nonadrenergic relaxation of tracheal smooth muscle. PMID- 6254156 TI - Fasting associated with decrease in hypothalamic beta-endorphin. AB - In rats that were fasted for 2 to 3 days there was a decline in hypothalamic, but not pituitary, beta-endorphin. There was no change in pituitary or hypothalamic adrenocorticotropin content as a result of fasting. Endogenous opiates may be involved in physiological adaptation to fasting. PMID- 6254157 TI - Gene transfer moves ahead. PMID- 6254158 TI - Modulation of epidermal growth factor receptors on 3T3 cells by platelet-derived growth factor. AB - Platelet-derived growth factor does not compete with epidermal growth factor (EGF) for binding to EGF receptors on the murine 3T3 cell surface, but it modulates EGF receptors in two ways: (i) it induces a transient down regulation of EGF receptors and (ii) it inhibits EGF-induced down regulation of EGF receptors. These data suggest a common cellular internalization mechanism for the receptors for both hormones. PMID- 6254159 TI - [Non-hormonal therapy for menopausal disorders: results of a multicentric double blind trial (author's transl)]. AB - A multicentric trial was conducted under double-blind conditions to assess the efficacy of veralipride in the treatment of menopausal disorders, when compared with placebo. Excellent or good results were obtained in 32 of the 40 patients (80 p. cent) with sudden flushes, after veralipride treatment, and only 17 of the 35 patients (48,5 p. cent) after placebo. In spite of the remarkable sensitivity of these disorders to placebo administration, the results are highly significant (p < 0-01) in favor of veralipride. Successful results after veralipride were more frequently noted in cases of natural menopause (21 out of 23 cases = 91,3 p. cent) than those with an artificial menopause (11 out of 17 cases = 64,7 p. cent). In psycho-functional disorders (anxiety, irritability, depressive syndrome), veralipride gave excellent or good results in 17 out of 32 cases, placebo in 8 out of 31 cases, a significant difference in favor of veralipride (p < 0,05). No significant modifications in biological parameters studied were noted, and only 2 cases of mild galactorrhea and mammary congestion were observed, though not reported by the patients. One patient complained of vertigo. Veralipride appears, therefore, to be the first non-hormonal therapy effective against disorders of the climateric. PMID- 6254160 TI - [A new therapeutic approach to menopausal sudden flushes and psychofunctional disorders (author's transl)]. AB - A group of 78 women with sudden flushes and associated disorders (pruritus vulvae, headache, anxiety, instability, depression, libido disturbances) related to the menopause were treated with one or two capsules of veralipride daily for 20 days. Excellent or good results were obtained in 54 of the 69 patients (78 p. cent) with sudden flushes, and 29 of the 57 cases (51 p. cent) with associated disorders. The difference in scores before and after treatment is very highly significant (p < 0.001). Clinical tolerance was good as only 2 cases of minimal galactorrhea. 2 cases of mastodynia, 3 cases with mild drowsiness, 2 patients with nervous tension or insomnia, 3 with digestive disorders, 1 with vertigo, and 1 with mild visual disturbances were observed. No modifications in the biological parameters studied were noted. Blood prolactin levels increased during treatment but returned to normal levels 4 days after discontinuation of therapy. No significant modifications in FSH, LH, E2, or E3 plasma levels were noted at the end of the study. Veralipride appears, therefore, to be the prototype for non hormonal therapy of menopausal disorders. PMID- 6254161 TI - [Vaginal smear cytology and hormonal tests before and after treatment with veralipride. Results in eleven cases (author's transl)]. AB - Vaginal smear cytology and hormonal tests were conducted in eleven patients in the natural menopause, before and after treatment with one capsule (100 mg) daily of veralipride alone for 20 days. Maturation of the vaginal epithelial cells unrelated to the degree of post-menopausal atrophy present was observed, without modification in plasma levels of gonadotropic LH, FSH and ovarian E2, E3 levels. PMID- 6254162 TI - [Clinical study of veralipride in menopausal sudden flushes (author's transl)]. AB - A double-blind clinical study was conducted to compare the therapeutic activity of veralipride and placebo in menopausal sudden flushes. Comparison of final numerical rate showed a statistical significant superiority for veralipride. Tolerance was excellent and no significant difference was observed between clinical side effects, or biological parameters studied (blood counts and differential, and blood bilirubin, transaminases, glucose, cholesterol, or creatinine levels) in the two groups. PMID- 6254163 TI - [Clinical study of the action of a new molecule, veralipride, on menopausal psychofunctional disorders (author's transl)]. AB - A preliminary open study was conducted in 20 women with menopausal sudden flushes to assess the effect of veralipride, administered as 100 mg/day for 20 days. In 15 cases, sudden flushes and night sweats were no longer present following treatment and behaviour had considerably improved. In the remaining 5 cases, sudden flushes were reduced in number and severity. A second study was then conducted in 40 women with the same symptoms, to compare the efficacy of veralipride and placebo under double-blind conditions. Successful results were obtained in 15 patients after veralipride and 5 after placebo, while treatment was a failure in 5 patients after veralipride and 15 after placebo. The difference is very significant in favor of veralipride (p < 0,01). Best results were obtained on sudden flushes, followed by mood and behavior disorders, with less consistent results in headache, pruritus vulvae, and palpitations. Clinical tolerance was good as only 4 cases of difficulty in falling asleep, 3 cases of mammary tension, and 2 cases of dryness of the mouth were reported. Biological parameters and vaginal smears were not modified by treatment. PMID- 6254164 TI - [Effect of veralipride on the estral cycle, genital tract, mammary gland and pituitary gland in female rats (author's transl)]. AB - A study of the potential biological effects of veralipride was conducted in female rats. A definite stimulating action on the mammary gland was noted, but doses of 5 to 20 mg/kg/day are required to produce secretion, which is varying from one animal to another. Follicular maturation is preserved, though there is an increase in the number of corpora lutea with more marked development in some of them. Progesterone impregnation of the uterus occurs in a variable way and then only at doses of 5 + 0 20 mg/kg/day. Vaginal mucification, from a reduction in estrogen in relation to progesterone impregnation, is noted after 1 mg/kg/day (though 25 p. cent of the animals still demonstrate vaginal keratinization after 20 mg/kg/day). Finally, degranulation of the carminophile cells of the anterior pituitary gland, occurs after 5 mg/kg/day. PMID- 6254165 TI - [An experimental study of veralipride (author's transl)]. AB - The administration of doses of 0,001, 0, 01, 0,1, and 1 mg/kg/day of veralipride to female rats produces a dose-related blocking effect on dioestrus. No histological changes are noted in the genital tract and mammary gland tissues after 0,001 and 0,01 mg/kg/day. Doses of 0,1 and 1 mg/kg/day block ovulation and the resulting estrogen impregnation modifies the appearance of the uterine glands and vaginal epithelium. Mammotropic effects, seen as a moderate hyperplasia but without galactogenic secretion, occur after 1 mg/kg/day only. PMID- 6254166 TI - [Pharmacological effects of veralipride on the mammary gland of female rats: a complementary study (author's transl)]. AB - Administration of 2 mg/kg/day of veralipride to intact female rats for 3 weeks provokes mammary gland development and, in some animals, the onset of secretory activity. These modifications do not appear after veralipride administration, under the same conditions, to castrated female rats. In castrated female rats previously conditioned by estradiol benzoate administration, some development of several acinous islets is observed in about half of the animals treated or not with veralipride. This suggests the development of a sensitivity of the mammary gland to the action of pituitary hormones, the secretion of which is stimulated by either castration or veralipride. It would seem that the absence of corpora lutea secretions prevented as great a mammary gland development as that observed in intact animals treated with veralipride. PMID- 6254167 TI - [Acute agranulocytosis. Clinical study of thirty-two cases (author's transl)]. AB - Acute agranulocytosis is a serious accident if the nature of the accident and the responsible drug are ignored or if it happens to a weak patient. Among thirty two cases of hospitalization, probably chosen according to their seriousness, the authors recall the diversity of the symptoms, the risk of the abuse of the "pyrazol compound" (70% of agranulocytosis) and the frequency of relapse (30%). The prognosis depends on the risk of infection. Septicemy is rare (15%), often foreseeable depending on the state of the patient. Agranulocytosis remains serious in spite of a wide range antibiotics administered in the early stages. PMID- 6254168 TI - [The abnormalities of carbohydrate and lipid metabolism in uremia. A study in 20 hemodialyzed patients (author's transl)]. AB - The glucose tolerance and serum lipids pattern were studied in 20 hemodialyzed patients after 8 and 12 hours of fasting. They all were non-obese uremics under 40 years of age. The test was conducted according to the nutritional conditions of the protocol of de Gennes. Fasting hyperglycemia and an abnormal glucose tolerance test were observed in 75% of the patients. The basal serum insulin levels were increased in 80% of the cases. 40% of the population studied exhibited significant hypertriglyceridemia after 12 hours and 65% after only 8 hours of fasting. Thus, this protocol was useful for detecting abnormalities in the metabolism of triglycerides in hemodialyzed patients with few baseline disturbances. The normal levels of serum triglycerides at 12 hours could be explained by 1) the relatively young age of the population studied and 2) dialysis with glucose free solutions. PMID- 6254169 TI - [Evolution of serum lipids during the first hours of an acute myocardial infarction (author's transl)]. AB - The evolution of serum lipids is investigated in 26 patients admitted in a coronary care unit less than 9 hours after the onset of an acute myocardial infarction. Blood samplings are made every 3 hours until the 15th hour after the onset of the infarction. The decrease of total serum lipids concentration is significant at the 9th hour (3rd hour : 8,45 +/- 0,58 g/l ; 9th hour : 7,74 +/- 0,36 g/l) ; that of triglycerides, at the 6th hour (3rd hour : 1,33 +/- 0,17 g/l ; 6th hour : 1,18 +/- 0,21 g/l) ; that of cholesterol is more delayed, at the 9th hour (3rd hour : 2,98 +/- 0,18 g/l ; 9th hour : 2,83 +/- 0,11 g/l). The proportion of alphalipoproteins increases, that of prebetalipoproteins decreases, that of betalipoproteins remains unchanged. There is no difference between the patients who received heparin and those who did not. Total lipids and triglycerides concentrations are lower in the group of patients with complications than in the group without complications. PMID- 6254170 TI - [Surgical treatment of myasthenia by thymectomy. A report on 248 cases (author's transl)]. AB - Good results were obtained in 80 p. cent of 248 patients seen after more than 15 months following the operation. Results are grouped as a function of the different characteristic features of the patients and three groups can be defined: failures, improvement, remissions. These results contradict those who assert that thymectomy is of no value for severe cases. Cervicotomy is performed for non-tumoral forms or for small tumors; sternotomy is reserved for large median thymomas; anterolateral thoracotomy for laterally located thymomas and tracheotomized patients. Postoperative tracheotomy is very rarely needed. Patients are followed-up by clinical signs and ergodynamometric tracings. The prognosis for the myasthenia is not affected by the presence or absence of germinating centres in the non-tumoral thymus, or by the benign nature of the thymoma. Small undiagnosed tumors may be discovered during operation. Treatment of recurrences is difficult. The myasthenia may be associated with other auto immune affections. The indication for operation in the purely ocular forms is debatable. Thymectomy may produce total remission even in severe cases, and may improve the results of medical treatment. Even in case of failure it can reduce the severity of the course of the disease. PMID- 6254171 TI - [Thymectomy for myasthenia gravis (author's transl)]. AB - The indications for thymectomy in the treatment of myasthenia gravis have changed over the years. Now it is considered in all but the mildest forms and in the elderly that are kept under medical management; 129 patients were treated surgically, 57 males and 78 females; respectively 30 and 17 per cent had a tumour and the average age was 35 years. The operation was carried out through a median sternotomy with no operative deaths but 3 late deaths and 70 per cent were improved or in remission. PMID- 6254172 TI - [Thyroid autonomous nodule. Surgical treatment and postoperative outcome, retrospective study of 102 cases (author's transl)]. AB - Follow-up of 102 patients operated upon for autonomous thyroid nodules is reported. Retrospective study of operative findings and aftermath of surgery clearly demonstrates that the patho-physiological concept of autonomous nodule does not snugly fit practical problems experienced with the management of such patients. The autonomous nodule can be a malignancy. Ipsilateral thyroid lobectomy seems more suitable than nodulectomy. Gross appearance of the thyroid remnant makes sometimes post-operative hormonotherapy unexpectedly advisable. From a theoretical point of view, post-operative thyroid scan, TSH assay and TRH test are mandatory, to assess recovery. PMID- 6254173 TI - [Articular chondrocalcinosis revealed by acute cervical symptoms simulating meningitis (author's transl)]. AB - Four cases of acute cervical pain with high fever and important stiffness of the cervical spine, leading to study the cerebrospinal fluid in emergency, are reported. All cases had elevated erythrocyte sedimentation rate. Recovery was obtained in all cases in a few days without treatment. The cerebrospinal fluid was normal in the three cases studied. In three patients the roentgenograms demonstrated calcified cervical cartilages, mainly in the atlas-axis joint, and osteo arthritis-like arthropathies. This syndrome, simulating meningitis revealed the calcium pyrophosphatecrystal deposition disease in the four cases. Crystal induced arthritis of the cervical spine is suggested but not demonstrated. PMID- 6254175 TI - [Assisted circulation during coronarography: advantages and limitations. A report on 63 cases (author's transl)]. AB - During 2588 coronarography examinations conducted over a period of 4 years, assisted circulation was employed in 63 cases to reduce the risks of the examination procedure in particularly debilitated patients. These high risk cases included 48 patients with unstable angina resistant to medical treatment and 45 cases of recent infarcts with complications. Mortality with assisted circulation was very low, in spite of the severe nature of the affections, but the authors use this technique in only a limited number of cases, mainly because of the risk of lower limb ischemia, and the possibility of using intravenous nitroglycerin and analgesia from neuroleptics for examination. For this reason the number of cases examined in this way has dropped from 4% in 1977 to 2% in 1978, though assisted circulation is still employed in certain particularly severe cases of angina, and for infarcts with complications. PMID- 6254174 TI - [Thymectomy for myasthenia gravis without thymoma. Long term results (author's transl)]. AB - The authors report an analysis of the long term results of 45 operated cases: 35 are symptom free in 7 cases more than 10 years later, 9 were improved and only one is worse. Operative mortality was nil; sternotomy is used in all cases. The authors insist on the reduction of therapy before attempting operation which should be carried out after 48 hours. PMID- 6254176 TI - [Study of 39 T1-T2 cervical stump cancers treated by a radio-surgical procedure (author's transl)]. AB - The authors present a casuistic study of 39 cervical stump cancers treated by combined radio-surgery at the Cancer Center in Nice. The protocol is similar to that of the uterine cervix. The overall five years survival rate is 68 per cent. Lymph node involvement occurred in 15 per cent of cases; non-sterilized cervical stumps represented 24 per cent. Two recurrences and two metastases were observed. PMID- 6254177 TI - [Mixed idiopathic cryoglobulinemia and glomerulonephritis (author's transl)]. AB - Mixed idiopathic cryoglobulinemia may be associated with renal failure. When this occurrence appears some characteristic lesions may be observed on renal biopsies. The authors describe a case of mixed idiopathic cryoglobulinemia with nephrotic syndrome and hypertension. Histologic data and immunofluorescence study of renal biopsies are similar to those described in the published literature. If antigen antibody complex seems to be for all authors the etiological feature of renal disease, the treatment to apply is not well known. The related case had been treated by plasmapheresis and the authors give their results to short and mean term. PMID- 6254178 TI - [Meckel's diverticular leiomyoma revealed by digestive hemorrhage. Preoperative diagnosis by selective arteriography (author's transl)]. AB - In connection with a case revealed by digestive tract hemorrhage per rectum, the authors emphasize the infrequency of Meckel's diverticula leiomyomas and stress the value of selective arteriography of the superior mesenteric artery as a means of pre-operative identification of these tumors. PMID- 6254180 TI - [Adult coeliac disease and very high IgA plasma level (author's transl)]. AB - The authors report a case of malabsorption syndrome with jejunal atrophy in a 63 years old woman. Coeliac disease was suspected from clinical and histological features, clinical evolution with diet, and presence of HLA B8 antigen. However, this case was very particular because the infiltration of lamina propria was very dense and especially composed of plasmocytes, and because there was a very important and polyclonal rise of immunoglobulin A (32 g/L) in the serum. A review of the literature allows to consider the immunopathology of coeliac disease. Such a case was never found among the adults. Two similar observations have been described in children. PMID- 6254179 TI - [Septicemia following infection of an endocardial electrode lead (author's transl)]. AB - The authors report one case of septicemia following the infection of a remaining endocardial electrode lead. From this observation and the literature's data, they are thinking that it is essential to remove the entire pacemaker system (electrode lead and generator) to cure this complication. They remind the different technics used to remove the endocardial leads. PMID- 6254181 TI - [Cholecystokinin and the control of hunger]. PMID- 6254182 TI - Case of the fall season. PMID- 6254183 TI - F-wave conduction velocity in alcoholic polyneuropathy. AB - We used the F-wave conduction velocities to estimate the motor nerve conduction along the proximal segment (spinal cord to knee) of the axon of tibial and common peroneal nerves in ten patients with alcoholic polyneuropathy and compared these to the motor nerve conduction velocities in ten normal subjects. All the studies so obtained showed a normal conduction in the proximal segments even though in three patients the distal nerve conduction values (knee to ankle) revealed moderate to severe neuropathy. These data support the hypothesis that in alcoholic polyneuropathy, motor conduction in proximal segments is not involved even though distal nerves show moderate to severe neuropathy. PMID- 6254184 TI - Ectopic ADH production before clinical recognition of small cell carcinoma of the lung. AB - Although the syndrome of inappropriate antidiuretic hormone secretion may be seen in several disorders, small cell bronchogenic carcinoma is probably the most commonly reported cause. We have reported a case of excessive production of ADH preceding the detection of the underlying small cell anaplastic bronchogenic carcinoma by nearly seven months, and suggest the possibility of using serum ADH levels in the diagnosis and management of such patients. PMID- 6254185 TI - Togavirus infection in rural Thailand. AB - Hemagglutination inhibition tests for antibody against chikungunya virus and the four dengue viruses were performed on a rural Thai village population. The 50% and 90% prevalence indices fell at about ages 3 and 15 for dengue virus exposure. This is considerably earlier exposure than comparable urban populations. The prevalence of chikungunya virus antibody was also age related with 50% prevalence at about age 45. PMID- 6254186 TI - A micro-neutralization test for flavivirus antibodies. AB - A micro-neutralization test for the detection of flavivirus antibodies is described. The test utilizes the PS line of cells in flat bottomed microtiter plates to detect the neutralization of cytopathic effect by specific antibodies. Cross-neutralization of flaviviruses found in Southeast Asia with homologous and heterologous hyperimmune mouse ascitic fluids revealed the test to be specific. The test is simple and inexpensive to perform. PMID- 6254187 TI - The activity of ketoconazole in mixed cultures of leukocytes and Candida albicans. AB - A system is described which allows the semi-quantitative investigation of the interaction between Candida albicans and leukocytes in culture with and without the addition of chemotherapeutic agents. Both polymorphonuclear leukocytes and macrophages avidly engulfed added yeast cells. However, they did not succeed in eradicating the fungus even when only 450 yeast cells were added to 3 X 10(6) leukocytes. This is probably due to several factors, including the decline in the functiontional capacity of the leukocytes with time in culture. The major way for the fungus to escape intracellular killing, however, seems to be the switch to the mycellial form in the presence of leukocytes. Engulfed yeasts produce germ tubes, grow out of the leukocytes and form hyphae which are much more resistant to the lytic action of the leukocytes. The leukocytes become necrotic through their interaction with the mycelia. Ketoconazole, a potent, orally active systemic antifungal agent inhibited the growth of C. albicans and completely suppressed the formation of mycelia in culture at very low concentrations (0.01 microgram ml-1). It was toxic to the leukocytes themselves only at 100 microgram ml-1. Addition of ketoconazole (10 (10-1.01 microgram ml-1) to mixed cultures of leukocytes and C. albicans allowed complete elimination of the fungus, probably because the leukocytes could easily remove the remaining yeast cells. The data show the usefulness of the system in the search for systemic antifungals and provide a possible explanation for the efficacy of ketoconazole in vivo. PMID- 6254188 TI - Metastatic trophoblastic disease presenting as a subarachnoid hemorrhage: report of two cases and review of the literature. AB - Trophoblastic tumors may present as subarachnoid or intracerebral hemorrhages in women of childbearing age. Although uncommon in Western countries, they constitute a significant percentage of metastatic lesions to the nervous system among Oriental women and usually follow molar pregnancies. Malignant transformation may occur at any time, but most frequently within a year of pregnancy. For this reason, close follow-up of women with molar pregnancies and subsequent prevention of pregnancy for one year is mandatory. Persistent serum human chorionic gonadotropin elevations are seen at some stage. Eighty percent of hydatidiform moles remit spontaneously, and the prognosis for persistent molar disease treated with chemotherapy and irradiation is good. The prognosis for choriocarcinoma, however, is less favorable. Subarachnoid hemorrhage may be the first and only sign of intracerebral bleeding into a metastatic lesion or leakage from a damaged vessel in which trophoblastic tissue has lodged. The triad of menstrual abnormalities, recent or remote pregnancy or abortion, and an acute cerebrovascular event with evidence of a mass lesion should suggest the diagnosis of metastatic trophoblastic disease in a woman of childbearing age. PMID- 6254189 TI - Analysis of arsenic in dental cements according to the silverdiethyldithiocarbamate photometric method - ISO 2590. AB - The reliability of the method for analysis for arsenic in dental cements according to the international standard ISO 2590 has been reinvestigated using nuclear tracer techniques and intercomparison of results obtained for the arsenic content of various cements by means of three different methods, i.e. the silverdiethyldithiocarbamate photometric method, neutron activation analysis and atomic absorption spectrophotometry. By means of the two methods first mentioned, results in rough agreement were obtained while the third method, i.e. atomic absorption spectrophotometry revealed lower contents. The interference of antimony in the analysis of arsenic in dental cements was quantitatively assayed. PMID- 6254190 TI - Unilateral odontodysplasia. AB - A case of malformation of five permanent teeth in the right maxilla is described. The asymmetrical malformations were probably caused by an early local trauma of the right maxilla. This trauma led to defective mineralization of the deciduous tooth germs, which was verified roentgenologically. The resulting early osteitic process caused injury to the permanent germs at a sensitive mineralization period. Mineralization disturbances of 13, 14, 15, 16 and 17 were established roentgenologically. In the other halves of the jaws the development was entirely normal. Endocrinological examination showed normal values and there were no signs of hypothyreosis or Turner's syndrome. Acute symptoms in the right maxilla at the age of 9 necessitated extraction of germs 14 and 16. As subsequent roentgenograms showed that 13 and 15 were not developing normally in respect of mineralization, these were extracted at, respectively, 12 and 13 years of age. For the same reason 17 was extracted two years later. The histopathological examination showed in all involved teeth a pronounced malformation with disturbances both of the morpho- and histodifferentiation of the various dental tissues. PMID- 6254191 TI - [Diagnostic criteria of hepatocellular carcinoma]. PMID- 6254192 TI - [Follow up after partial gastric resection (author's transl)]. PMID- 6254193 TI - [Problems in follow-up after total gastrectomy (author's transl)]. PMID- 6254194 TI - [Patient care after acute pancreatitis (author's transl)]. PMID- 6254195 TI - [Care of the patient with an intestinal stoma (author's transl)]. PMID- 6254196 TI - [Aggressive fibromatosis of the desmoid tumor type. Treatment and follow-up (author's transl)]. PMID- 6254197 TI - [The Colles' fracture (author's transl)]. PMID- 6254198 TI - [Postoperative treatment of tibia shaft fractures (author's transl)]. PMID- 6254199 TI - [Treatment of vertebral column injuries (author's transl)]. PMID- 6254200 TI - [Postoperative care and follow-up of hip joint arthroplasties]. PMID- 6254201 TI - [Postoperative care after knee surgery (author's transl)]. PMID- 6254202 TI - [After care of scar formation]. PMID- 6254203 TI - [Postoperative care problems in the surgery of cerebro-vascular diseases (author's transl)]. PMID- 6254204 TI - Lung metastases from a primary hepatocellular carcinoma. PMID- 6254205 TI - Compartmentalization of adenosine 3':5'-monophosphate-binding proteins in human platelets. PMID- 6254206 TI - Parallel inhibition of ristocetin and polycation-induced platelet agglutination. PMID- 6254207 TI - Dose-response, sex difference, and the effect of bran in dimethylhydrazine induced intestinal tumorigenesis in rats. PMID- 6254208 TI - The effects of aflatoxin B1 on some testicular and kidney enzyme activity in rat. AB - The effects of chronic intra-peritoneal administration of aflatoxin B1 on the activity of alkaline and acid phosphatases; glutamic oxaloacetate (GOT) and pyruvate transaminases (GPT); 5'-nucleotidase and lactic dehydrogenase enzymes were monitored in the testis and kidney of adult albino rats. Results showed that aflatoxin B1 depressed the activity of alkaline phosphatase in both tissues, but increased that of acid phosphatase in only the testis. While GOT and 5' nucleotidase were inhibited, GPT and lactic dehydrogenase activity was enhanced by this carcinogen. These responses were similar for the testis and kidney. The above findings coupled with the microscopical observation of the testis tissue seem to indicate that the essential lesion of this toxin on the testis may be a modification of the enzymes of germinal cells resulting from a gradual depletion of the latter. Furthermore, the results appear to show that by and large, aflatoxin B1 exerts only slightly different effects on the testis and kidney at the enzyme level. PMID- 6254209 TI - [Combined Wilms' tumor therapy (author's transl)]. AB - From 1967 to 1979, 40 children with Wilms' tumor were given a therapy comprising irradiation, operation and chemotherapy. Till 1972 preoperative irradiation was performed delivering a dose of 20 Gy followed by operation and actinomycin-D. The postoperative irradiation dose was 20 or 30 Gy. Of 22 patients died 7. Since 1973, therapy depends on age and tumor volume and consists in a combination of multidrug therapy, operation and irradiation (25 to 35 Gy). Of 19 children, 18 are still alive. No irradiation was given to patients younger than 1 year in stages I and II and to older children in stage I. PMID- 6254210 TI - [Radioprotective effectiveness of the paramunity inducer "pind-avi": investigation using the model "protective tetanic vaccination in mice" after exposure to X-rays (author's transl)]. AB - The model "protective tetanic vaccination in mice" was used in order to try whether the paramunity inducer Pind-Avi may diminish or suspend radiation-induced immunosuppression. The radioprotective effect was ascertained from the different results of immunization in mice exposed to radiation after pretreatment with either Pind-Avi or placebo. The dose delivered amounted to 300 R. Tetanus toxoid was used for immunization. Effectiveness of the tetanic vaccination was analysed by means of load tests with 10 LD50 tetanus toxin, and of antibody determination with passive hemagglutination. Evidence was shown of significant radiation protection following subcutaneous application of Pind-Avi once a day during three days before of after exposure. Efficiency in mice treated with Pind-Avi amounted to 75% (pre-irradiation treatment) and to 43% (postirradiation treatment), whereas the efficiency in controls was zero in all cases. Thus, it was possible with Pind-Avi to suspend radiation-induced immunosuppression within a period of 3 days before or after radiation exposure, not only by means of prophylactic but also by therapeutic administration. PMID- 6254211 TI - Prognostic value of doubling time in lung cancer. AB - The volume doubling time (DT) of 27 measurable primary pulmonary carcinomas was calculated. The prognostic value of the DT was analysed in relation to survival, age, initial size of the tumour, histology, duration of symptoms, and treatment. The survival was longest in slow-growing carcinomas. Small-cell carcinomas and other anaplastic carcinomas had the shortest DT. A close correlation was found between DT, survival, and Feinstein's symptom-staging. PMID- 6254212 TI - [Analysis of the toxicity and radioprotective effect of the chemical radioprotector WR 2721 in dogs (beagles). Part 2: Radioprotective effect of WR 2721 (author's transl)]. PMID- 6254213 TI - Occurrence of hepatic amoebiasis in rats inoculated intracaecally with a virulent strain of Entamoeba histolytica. PMID- 6254214 TI - Development of a kit for the assay of haemagglutination inhibition antibodies to flaviviruses using formalinized goose erythrocytes. AB - Haemagglutination inhibition (HI) test using goose erythrocytes (GRBC) is the method of choice for screening antibodies to various arboviruses. This test makes use of fresh GRBC preserved in dextrose-gelatin-veronal (DGV). We have tried formalinizing GRBC and have found that such cells can retain the surface property of being agglutinated by arboviruses and, therefore, can be used in haemagglutination (HA) and HI tests. Unlike fresh cells preserved in DGV, formalinized cells can be preserved for a long time without haemolysis or loss of sensitivity. They can also be frozen or lyophilized. Making use of these properties, a kit has been developed for the assay of HI antibodies to some members of the flavivirus group. Use of this kit simplifies the HI test and enables it to be carried out routinely by any hospital or laboratory to screen arboviral infections. PMID- 6254215 TI - Immunogenicity of axenic Entamoeba histolytica antigen and its fractions. AB - Amoebic antigen prepared from axenic Entamoeba histolytica (NIH:200 strain) grown at 37 degrees C in TPS I medium was chromatographed on a Sephadex G-200 column. Three fractions (F-I, F-II, F-II) were obtained, the molecular weights of which ranged from 650,000 to 1,450. Fractions were concentrated by lyophilization and antisera against each fraction and whole antigen were raised in rabbits. Partially purified fractions were used in various serological tests and their reactivities were compared with whole amoebic antigen. Main haemagglutinating and precipitating activities were confined to Fraction I, which had 14% of total protein and the highest molecular weight (650,000). 5 micrograms/ml of protein contained in this fraction gave antibody titres comparable to those obtained with whole antigen with 40 micrograms/ml or protein. Other fractions, although they had precipitin activity, lacked haemagglutinating activity. The protective efficacies of these fractions are being investigated in our laboratory. PMID- 6254216 TI - Amoebic antigen in immunodiagnosis and prognosis of amoebic liver abscess. AB - The detection of amoebic antigen by counterimmunoelectrophoresis is very useful and important in the immunodiagnosis of invasive hepatic amoebiasis. The antigen was demonstrated in 115 (92%) of 125 patients with amoebic liver abscess. All the 19 cases which showed Entamoeba histolytica in the 'pus' were positive for the antigen and 96 of 106 samples negative for the parasite by smear and culture were also positive for the antigen. In none of the controls was a falsepositive reaction obtained. 12 of 13 liver biopsy specimens were also positive for antigen. The persistence or disappearance of the antigen from the liver pus biopsy specimens was investigated: the antigen disappeared in eight of the 33 cases followed for intervals up to 60 days after cure, suggesting that this is also an important additional criterion for evaluating the prognosis of the disease. Further, it has been shown that amoebic infection is followed by the appearance of specific antigen or antigenic substances in the serum which were demonstrated in 23 of 89 proved cases of amoebic liver abscess cases. Its possible role in immune complex formation and the pathogenesis of the disease is discussed. PMID- 6254217 TI - Experimental amoebic infection in guinea-pigs immunized with low grade amoebic infection. AB - Guinea-pigs were immunzied with a low grade amoebic infection, either intracaecally or intramesenterically. The immunized animals were challenged with a virulent strain of Entamoeba histolytica. Some of the animals, immunized via the intracaecal route were challenged repeatedly. 10 to 30% of immunized animals developed caecal lesions compared with 92.8% of non-immunized animals. The percentage of protection in animals challenged repeatedly was greater than in those challenged once. Neither immunized nor non-immunized guinea-pigs developed hepatic abscesses. It appears that prior low grade infection could lead to resistance to subsequent amoebic challenge. PMID- 6254218 TI - Hepatitis-B virus determinant in patients with liver disease in Malawi. PMID- 6254219 TI - IgM responses to hepatitis-A virus and hepatitis-B core antigen in acute and chronic liver disease in Malawi; possible role of non-A, non-B, hepatitis. AB - Of 33 patients with acute hepatitis in Malawi, 21 had infection by hepatitis-B virus (HBV), five by hepatitis-A virus (HAV) and seven, who had no markers of current HBV or HAV infections, were probably infected by the agent(s) of non-A, non-B, hepatitis. 87 of 88 sera from persons without liver disease contained antibody to HAV and 49 antibody to hepatitis-B surface antigen (anti-HBs) (six were positive for hepatitis-B surface antigen). The diagnosis of recent infection by HAV was made by detecting HAV-specific IGM in single serum samples and, although such tests showed that HAV caused acute hepatitis, its absence in patients with chronic liver disease suggests that, unlike HBV, infection by HAV does not play a role in chronic liver disease in Malawi. Anti-hepatis-B core antigen (anti-HBc)-specific IgM was detected in 19 of 21 patients with acute HBV infection, in three of five HbsAg-positive patients with cirrhosis, but in none of five HbsAg-positive patients with hepatoma. PMID- 6254220 TI - Comparison of IHA test for amoebiasis on serum and filter paper specimens. PMID- 6254221 TI - Culture of human endothelial cells. PMID- 6254223 TI - Induction of active immunity to TGE in neonatal pigs nursing seropositive dams. PMID- 6254222 TI - Canine parvovirus: update. PMID- 6254224 TI - Field evaluation of an intranasally administered canine parainfluenza-Bordetella bronchiseptica vaccine. PMID- 6254225 TI - Hepatitis due to Clostridium perfringens in a dog. PMID- 6254226 TI - Rapid onset of immunity in cattle after intramuscular injection of a modified live-virus IBR vaccine. PMID- 6254227 TI - Origin of canine parvovirus. PMID- 6254229 TI - Cryptosporidia associated with rotavirus and an Escherichia coli in an outbreak of calf scour. PMID- 6254228 TI - Unusual sequelae to feline enteritis vaccination in a dog. PMID- 6254230 TI - Freeze-dried infectious bronchitis haemagglutinating antigen. PMID- 6254231 TI - Detection of coronavirus in neonatal calf diarrhoea by HEHA. PMID- 6254232 TI - New emerging viral zoonoses. AB - New developments in the field of viral transmission from animal to man can be divided into four areas of study. First are the new viral zoonoses such as diseases caused by rotaviruses, Lassa virus and the animal orthopox viruses which will be more prevalent after the cessation of mandatory vaccination against smallpox. Secondly are the numerous ubiquitous viruses, such as adeno and herpesviruses, which in healthy animals lead only to clinically inapparent infections. A typical example of the third area is the recombination and hybridisation between animal and human influenza type A viruses. The final area is concerned with the transmission of viral zoonoses to man through food of animal origin. PMID- 6254233 TI - A simple and rapid immunoperoxidase test for the detection of virus antigens in tissue culture. PMID- 6254234 TI - Canine parvovirus: safety and efficacy of attenuated feline panleucopenia vaccine. PMID- 6254235 TI - Feline leukaemia virus diagnosis. PMID- 6254236 TI - The isolation of parainfluenza 3 virus from free-living African buffalo (Syncerus caffer). PMID- 6254237 TI - Clostridium perfringens type E enterotoxaemia in rabbits. PMID- 6254238 TI - [Specific immunoprophylaxis trials with calves against foot-and-mouth disease]. AB - Studies were conducted on vaccination of different age groups of calves with monovalent and biovalent vaccine against foot-and-mouth disease using various immunization patterns. The studies showed that passive immunity of calves impedes the building up of solid immunity. It is recommended on the basis of comparative studies of different immunization schemes to vaccinate calves under 6 months of age with double vaccine dose and to revaccinate them 1--2 months later. It was shown that calves aged 6 to 12 months react to vaccine against foot-and-mouth disease as adult animals but revaccination is also recommended to build up solid immunity. The influence is discussed of various factors hindering the building up of solid post vaccination immunity in young animals following vaccination with vaccine against foot-and-mouth disease. PMID- 6254239 TI - [New ethyl-m-aminobenzoate salts as temporary anesthesia agents in trout raising]. AB - Various ethyl-m-aminobenzoate salts were synthesized to conduct biological tests on a total of 170 trouts (rainbow, siven and Balkan) with a view to establishing new agents for brief narcosis. Of these excellent effect manifested phosphate and hydrochloride, the latter even excelling the effect of the well known preparation MS-222 which is a salt of methane sulfonic acid. The tested concentrations of the substances ranged from 1:20 000 to 1:80 000 and the exposure length--from 10 to 30 min. The recommended working concentrations are from 1:40 000 to 1:60 000 narcosis setting on within a few minutes. Respiration of narcotized fish remains almost unchanged. The fish recover completely when put in running water. It is inferred that fish narcosis can be used for their temporary immobilization in case of mannual operations. PMID- 6254241 TI - Further epidemiological investigations on subacute sclerosing panencephalitis (SSPE) in Romania. AB - The epidemiological study of 101 SSPE cases revealed the following aspects: a) an increase in the annual SSPE incidence, in relation to the improvement of detection possibilities; b) the preponderent involvement of male children and of children having experienced measles within the first 6-18 months of life; c) the high incidence of SSPE cases in families with several children, the patient being the 2nd or 3rd sibling; d) a mean interval of 50.1 +/- 32 months between acute measles and the onset of SSPE; e) the clustering of cases in terms of the epidemic year when acute measles had occurred. There were no modifications in SSPE epidemiology during the first 6 months after the initiation of mass antimeasles vaccination. PMID- 6254242 TI - Electron microscopic observations concerning the action of some aromatic compounds on the morphology of Sendai virus. AB - The interaction between Sendai virus and some fluorescent aromatic compounds with reactive chemical groups ( a vinyl-sulfonic and an isocyano naphthalic acid derivative) leads to alterations of the surface and inner structure of virus corpuscles. The intensity of the changes depends on the type of reactive group. No such morphological changes were induced by 1-amino-2-anthraquinone-sulfonic acid, a compound whose interaction with the virus is exclusively of physical nature. PMID- 6254240 TI - Synovial sarcoma of the abdominal wall. Light microscopic, histochemical and electron microscopic investigations. AB - A synovial sarcoma of the abdominal wall in a 56-year old woman showed the typical features of this tumor type. Histologically a characteristic biphasic cellular pattern with epithelium-like cell complexes and sarcomatous spindle cell areas was found. The histochemical examination revealed that tumor cells synthesize glycoproteins and weakly acid glycosaminoglycans (mainly hyaluronic acid). Electron microscopically the tumor cells in epithelium-like cell islets were sometimes arranged in gland-like formations with microvilli at the luminal side, specialized intercellular junctions and a peripheral basement membrane-like condensation of the ground substance. There was no fundamental cytological difference between cells of epithelium-like and spindle cell areas. Generally the tumor cells imitated cells of the synovial membrane and we found no evidence for origin from cells of the nerve sheath. Because of the submicroscopic relationship and histochemical similarities of synovial sarcomas and mesotheliomas we suggest that they should be united in a group of sarcomas with possible biphasic cellular pattern, while preserving their clinicopathologic definition. PMID- 6254243 TI - Isolation of parainfluenza virus type 3 from an infant with meningoencephalitis. AB - A parainfluenza virus type 3 strain was isolated from the cerebrospinal fluid of an infant with a clinical diagnosis of meningoencephalitis. Specific HAI antibodies to parainfluenza virus type 3, ranging in titer from 1/80 to 1/160 could be detected in the infant's serum. A 2-fold rise in the level of complement fixing serum antibodies-from 1/16 at the first to 1/32 at the second collection was recorded. PMID- 6254244 TI - Polypeptide changes in Sendai virus-infected cells. AB - The appearance of virus-specific proteins in Sendai virus-infected chick embryo fibroblasts and chorioallantoic membrane cells was studied by high resolution SDS polyacrylamide gel electrophoresis. All the structural Sendai virus polypeptides, as well as the nonstructural virus polypeptide termed B could be identified in the total lysates of infected cells. Only the structural virus polypeptides NP, P and M were found in the ribosome fraction of virus-infected cells; these additional polypeptides were removed from the ribosome surface by washing the 1 M NH4Cl. PMID- 6254245 TI - Extrarespiratory localizations of parainfluenza viruses. AB - Two hemagglutinating and hemadsorbant agents-serologically identified as parainfluenza viruses type 3-were isolated from the cerebrospinal fluid of a 10 month-old infant with meningoencephalitis and from the urethral secretion of a male patient with nonbacterial urethritis. Parainfluenza virus antigens types 1, 2, and 3 were detected by indirect immunofluorescence reactions in cells exfoliated in the vagina of women with genital neoplasia or common gynecopathies. PMID- 6254246 TI - Cell transformation in vitro by herpes simplex virus (HSV). AB - Data are presented on morphological and biochemical cell transformation in vitro induced by HSV. The results of some investigations on the oncogenic potential of different HSV strains, performed in the "Stefan S. Nicolau" Institute of Virology, are also reviewed. Several hypotheses concerning the mechanism of HSV induced cell transformation in vitro are discussed. PMID- 6254248 TI - Infection of rat cells by avian sarcoma virus: factors affecting transformation and subsequent reversion. PMID- 6254247 TI - Restriction of murine leukemia proviral gene expression in somatic mouse cell hybrids. PMID- 6254249 TI - The white pock mutants of rabbit poxvirus. II. The early white pock (mu) host range (hr) mutants of rabbit poxvirus uncouple transcription and translation in nonpermissive cells. PMID- 6254251 TI - The small-t protein of SV40 is required for loss of actin cable networks and plasminogen activator synthesis in transformed rat cells. PMID- 6254250 TI - Receptors for encephalomyocarditis virus on murine and human cells. PMID- 6254252 TI - Identification of a normal vertebrate cell protein related to the p21 src of Harvey murine sarcoma virus. PMID- 6254253 TI - Rous sarcoma virus precursor protein pr 76 is processed in avian sarcoma virus transformed mammalian cells after fusion-injection of viral protein p 15. PMID- 6254254 TI - Inhibition of measles virus replication by cyclic AMP. PMID- 6254256 TI - The oncogenicity of avian adenoviruses. I. An unusually large number of viral DNA molecules in some tumors, and virus-specific T-antigenic proteins. PMID- 6254255 TI - Transformation-related proteins associated with Kirsten sarcoma virus. PMID- 6254257 TI - The oncogenicity of avian adenoviruses. II. The arrangement of the viral DNA in tumors and transformed cells. PMID- 6254258 TI - Different serotypes of B-tropic murine leukemia viruses and association with endogenous ecotropic viral loci. PMID- 6254259 TI - Polymorphism among the major core proteins of C57BL B-tropic murine leukemia viruses. PMID- 6254260 TI - Phosphorylation of pp60src and the cycloheximide insensitive activation of the pp60src-associated kinase activity of transformation-defective temperature sensitive mutants of Rous sarcoma virus. PMID- 6254261 TI - Morphologic changes in the rabbit SIRC cell line induced by simian sarcoma associated virus. PMID- 6254262 TI - [Continuous lymphoblastoid cell lines in virological research]. PMID- 6254264 TI - [Karyotype change in human cell cultures in the process of the reversion of Coxsackie B virus sensitivity]. AB - The study was done on a subline of cells reverting to sensitivity to Coxsackie B3 virus after treatment of J-41 cells resistant to this virus with a homogenate prepared from the sensitive J-96 cell culture. Cytogenetic examinations of this cell subline showed its karyological characteristics to approach those of the sensitive J-96 culture. The modal number of chromosomes and the number of chromosomes 2, 9, 11, 12, and 21 were completely restored and marker chromosomes typical of the sensitive culture appeared. In the reverted subline there was almost no marker chromosomes peculiar for the resistant J-41 culture. In addition, a decrease in the number of chromosomes 1 and 19 replicas as compared with J-96 and J-41 culture cells and the presence of marker chromosomes not found in the original cultures indicate that this subline has its own distinctive characteristics. PMID- 6254263 TI - [Comparison of a few methods for detecting antibodies to the bovine leukemia virus]. AB - A comparative analysis of the results of bovine sera examinations by three methods for the detection of antibody to bovine leukemia virus (BLV): VSV BLV pseudotype neutralization test (PTNT), gel immunodiffusion using BLV glycoprotein antigen (GIDgp) and BLV 125I-p24 radioimmunoprecipitation (RIPp24), was performed. The results of all the three methods were in good correlation. The PTNT sensitivity was shown to exceed essentially all the other methods of BLV antibody detection. There was a definite correlation between the serum titer in PTNT and the possibility of antibody detection in RIPp24 and GIDgp. The potentials of these methods for diagnosis of BLV infection in animals are discussed. PMID- 6254265 TI - [Spontaneous contamination of primary green monkey kidney cell cultures by foamy virus]. AB - Examinations of 1653 batches of green monkey kidney cell cultures revealed contamination with foamy virus (FV) in 243 (16%) batches. From some of these cultures 65 strains of virus belonging to two serotypes were isolated. Tests on sera from 1122 monkeys revealed antibody to FV in 985 (87.8%) animals. No correlation between the presence of antibody in the serum and virus recovery from monkey kidney cell cultures was observed, however. This might be due either to the lack of the virus in the kidneys or to the failure in its isolation from primary cultures. Passages of cell cultures were shown to facilitate additional recovery of FV. These experimental results may be used for screening and selection of FV-free cultures and for control purposes in the course of vaccine manufacture. PMID- 6254266 TI - [Degradation of Anacystis nidulans cells by the action of cyanophage AS-1]. AB - The sequence of degradation of the photosynthetic apparatus of Anacystia nidulans after virus infection was studied using different methods. In the first stages of pathogenesis changes in the structure and functional activity of the photosynthetic apparatus were shown to be insignificant. At the stages of marked degradation the system of oxygen release and light collecting complex are destroyed gradually. The reaction center of photosystem I is the most resistant to degeneration. PMID- 6254267 TI - [Persistence of attenuated poliomyelitis virus in the organs of vaccinated animals]. AB - Experiments in cotton rats weighing 60-80 g orally vaccinated with gradually decreasing doses of live poliovaccine type II causing immunological changes of varying intensity demonstrated the attenuated poliomyelitis virus to penetrate the CNS, lungs, and spleen quite regularly. The virus could be isolated from the cytoplasmic extracts of these organs for up to 45 days, from the spleen for 60 days. Penetration of the virus into the CNS did not result in the development of disease. The long-term persistence of the virus in the organs was accompanied by the development of inflammatory-degenerative changes in the CNS and in some cases by pneumonia. PMID- 6254268 TI - [Characteristics of the type C virus produced by Rous sarcoma virus-transformed hamster cells]. AB - Production of hamster type C virus in Rous sarcoma virus-transformed hamster cells is described. This virus preparation was shown to contain the antigen of the major inner protein of avian type C viruses (p27). The population of virions produced by such cells consists of either of virions of two types (99%--99.9% virions type C of hamster and 0.1%--1% virions the core capsule of which is formed from Rous sarcoma virus p 27) or of virions phenotypically mixed with regard to the major inner protein. The latter possibility seems less likely. PMID- 6254270 TI - [Sedimentation and electron microscopic characteristics of RNA isolated from a highly concentrated suspension of Sendai virus]. AB - Sedimentation analysis in a lineal (5%--30%) sucrose concentration gradient of an RNA preparation isolated from a highly concentrated Sendai virus suspension revealed an additional peak with sedimentation coefficient 69S apart from previously known peaks of 46S (genome RNA), 30S and 18S (incomplete virus RNA). Electron microscopy methods showed the single-stranded molecules of 46S RNA to have a marked hairpin structure. Molecules of double-stranded 69S RNA have a specific structure: lineal parts alternate with areas in the form of rosettes. It is suggested that molecules of of 69S RNA are a product of incomplete hybridization between "plus" and "minus" complementary chains of virion RNA. PMID- 6254269 TI - [Use in experimental virology of methods of evaluating animal behavior for the study of the pathogenesis of neuroviral infections]. PMID- 6254271 TI - [Synthesis of RNA-containing virus-specific components in L cells persistently infected with SV5 virus]. AB - An analysis of RNA-containing virus-specific structures was performed in the course of the establishment of persistent infection with SV5 virus in L cells. It was observed that up to the 11th passage in the LSV5 system, the same virus specific structures were synthesized as in acute infection. At the level of the 18th passage synthesis of intracellular RNP was reduced and high 3H-uridine incorporation into light structures was observed. In the last passages examined (25th and 31st), the structures with rho 1.18--1.17 g/ml were predominant. The sedimentation RNA analysis (the 3rd, 6th, and 11th passages) revealed 50 S, 35- 32 S, 24 S, and 18 S RNA. At later passages (25th and 31st), synthesis of 35 S, 24--22 S and lighter RNAs was dominant. The possibility of relationship between reduced 50 S RNA synthesis and low infectivity of intracellular virus is discussed. PMID- 6254272 TI - [Statistical evaluation of the results of titrating viral infectivity by the plaque method]. PMID- 6254273 TI - [DNA from cells infected with herpes simplex virus and from human tumors as an inducer of synthesis of a new nonvirion antigen]. AB - DNA from herpes simplex virus type II (HSV-II)-infected cells isolated by using SDS, phenol, and pronase as well as by a new method of Pignatti et al. from triton X-100-NaCl-supernatant was shown to be capable to induce production of an early nonvirion (new) antigen in sensitive systems of Vero, RS-537 cells and others. It was also established that as a result of transfection of DNA recovered from 13 speciment of cancer tumors of the cervix and ovaries (9 tumors contained the new antigen and 4 were free from it), the new antigen associated with HSV-II was synthesized in 8 cases in the sensitive cells as early as 6 hours postinoculation whereas no viral antigens could be detected by this time. No viral antigens could be detected within 24 hours either, with the exception of 3 cases where CPE also developed by 24 hours indicating the appearance of the virus. DNA recovered from normal tissues of the cervix was incapable of inducing the new antigen. PMID- 6254275 TI - [Detection of bovine leukemia virus in tissue cultures]. AB - Syncytium formation was demonstrated in cocultivation of cow and sheep embryo kidney cells with peripheral blood lymphocytes from leukemic cattle. The beginning of this phenomenon was observed at 3--4, and maximum development at 6- 8 days of cocultivation. Lymphocytes of 22 out of 24 leukemic animals were capable of inducing syncytium formation. Parallel examinations of cocultivated cells by the direct immunofluorescence procedure using fluorescent antibodies from sera of leukemic cows gave positive results in 23 our of 24 cases, whereas lymphocytes of 12 normal cows never induced either syncytium or specific antigens. PMID- 6254274 TI - [Study of enteroviruses in different environments using guanidine-dependent variants]. AB - Guanidine-dependent variants of enteroviruses were used as indicators for the study of the effectiveness of environmental object purification processes. The dependence of virus replication on guanidine provides complete safety of the virus for man and selective virus isolation from the objects under study. The use of the indicator virus allows to perform quantitation studies. Two examples of practical utilization of a guanidine-dependent variant of poliomyelitis virus (evaluation of the effectiveness of sewage purification from enteroviruses, and milk pesteurization system) are presented. The advantages of using guanidine dependent variants of enteroviruses for modeling and investigations of virological processes in the environment and potentials of the method are analysed. PMID- 6254276 TI - [Isolation of the poliomyelitis virus from cases of acute respiratory diseases]. AB - Poliomyelitis virus was shown to be able to cause human outbreaks of acute respiratory diseases (or "minor illness") running without clinical symptoms of the involvement of the central nervous system. It is most likely that the outbreaks were caused by vaccine poliomyelitis-virus strains circulating in the human population. PMID- 6254277 TI - [New aspects in the pathogenesis and in the course of type-I-diabetes mellitus (author's transl)]. PMID- 6254278 TI - [Hormone receptors in research and their clinical application (author's transl)]. AB - Experimental investigations and clinical studies stress the importance of hormone receptors in basic research and clinical investigation. The study of LH-RH receptors in the anterior pituitary of rats resulted in the possible use of LH-RH analogues as competitive inhibitors of the releasing hormone. This resulted in the development of a new concept of fertility control. The investigation of steroid hormone receptors in the anterior pituitary of rats provided a basis for the mechanism of action of steroids in modulating the release of gonadotropins and prolactin from the adenohypophysis. The determination of cytoplasmatic oestrogen-receptor and progesterone-receptor levels, combined with the estimation of the nuclear oestrogen-receptor content allows an improved selection of patients for endocrine therapy of breast tumours. Our results on the investigation of steroid receptors in the human endometrium suggest that receptor assays are of prognostic value and provide a guide for selecting patients with cancer of the body of the uterus for adjuvant hormone therapy. In addition, the present data combine to suggest that receptor assays may be useful in other endocrine diseases and in cases of unexplained sterility. PMID- 6254279 TI - [Disorders of calcium metabolism]. PMID- 6254280 TI - [Aetiology and importance of viral diseases of the respiratory tract (author's transl)]. AB - After discussion of the epidemiological situation of acute respiratory diseases and their economic consequences, and after a survey of clinical signs and symptoms, a review is given of the most important viral agents causing such diseases. That are influenza, parainfluenza, respiratory syncytial, adeno, corona, REO, and rhino viruses, which are prevalent in the respiratory tract. Viruses predominantly localized outside of the respiratory tract as well as bacteria and bacteria-like microorganisms are only shortly mentioned. Most weight is given to virological problems (morphology, antigenic structure), to pathogenic property and importance of viruses causing acute respiratory diseases. PMID- 6254281 TI - [Morphological changes of guinea pig lungs after aerosol application of lipiodol ultrafluid (author's transl)]. AB - The morphological lung changes of guinea pigs, exposed about 10 days to an aerosol of lipiodol ultrafluid were investigated with light microscopy and enzyme histochemistry 3, 10, 18, 25, 32, 38 and 46 days later. There was a prominent diffuse ore focal thickening of alveolar septa by accumulations of macrophages. Important are changes on the vascular endothelium of muscular pulmonary arteries with swollen and vacuolised endothelial cells. Around pulmonary veins accumulations of lymphocytes were detected. With histochemistry slight increase of phospholipids in alveolar epithelial cells was observed predominantly in the first three days after aerosol application. The intensity of the morphological changes showed a time dependent biphasic cycle with peaks of maximum at the 10th and 38th day after applicationof aerosol. PMID- 6254282 TI - [Action mechanism of the thyroid hormone in the heart cell--interaction of the thyroid hormone and catecholamines]. AB - The thyroid hormones change the adrenergic reactivity of the myocardium. Since a series of cardiac functions, among others also ways of metabolism such as glycogenolysis and lipolysis underlie an adrenergic regulation, changes of the state of the thyroid gland manifest themselves on them. Investigations at the system of the beta-adrenergic receptor-adenylate-cyclase have shown that in hyperthyreosis and the beta-adrenergic number of receptors is increased by more than double. Moreover, references were got that the thyroid hormones have an influence on the coupling of the receptor to the catalytic subunit of the adenylate cyclase and a regulatory subunit of the enzyme which is regulated by guanine nucleotides. These findings help in the clarification of the causes for the changed reaction to the beta-adrenergic stimulation of the heart. PMID- 6254283 TI - [Behavior of thyroid hormones, corticosterone, adrenocorticotropic hormone and insulin in the plasma of the rat under stress conditions]. AB - In male Wistar rats the behaviour of the plasma concentrations of thyroid hormones, corticosterone, adrenocorticotrophic hormone and insulin was examined in the course of a hypokinase stress of 6 weeks duration. Blood was taken after a stress of 1, 3 and 6 weeks. In these cases in thyroid hormones a decrease of the thyroxine (T4) and an increase of the triiodothyronine (T3) appeared. In an increased need of energy of the organism apparently a more rapid peripheral conversion of T4 to the more active metabolic T3 takes place. Only after a longer stress the deficit of thyroid hormone is equalized via the regulating circle hypothalamus-hypophysis-thyroid gland. The hormones ACTH and corticosterone which are connected together in the regulation system hypothalamus-hypophysis-adrenal cortex, after one week slightly increase in the plasma of rats and clearly decrease after a stress of 3 weeks. This shows that in a longer stress load apparently an exhaustion of the bioenergetic reserves of the organism develops. At last under long-term stress a significant decrease of the plasma insulin level was found. The decrease of insulin might be conditioned by an endogenic liberation of catecholamine. PMID- 6254285 TI - [Acetylcholinesterase activity in visual cortex structures during early visual deprivation]. AB - By means of quantitative histochemical methods it has been shown that an early photic deprivation (animals kept in a dark chamber for two months after their birth) leads to a decrease in the activity level of acetylcholinesterase (AChE) in the visual area of the cerebral cortex. With the recovery of the visual function (animals kept in normal photic conditions for two weeks) the AChE activity becomes markedly normalized. The obtained data allow to suggest that the decrease in AChE activity due to deprivation is functionally determined. PMID- 6254284 TI - Further studies on the effect of cholecystokinin and secretin on the content of cyclic AMP, cyclic GMP, protein and calcium in pure pancreatic juice of dogs. AB - The present work deals with the time course of pancreatic secretion of cyclic AMP, cyclic GMP, calcium and protein in response to cholecystokinin (CCK) and secretin (S). Three dogs with gastric and duodenal Thomas cannulae were given 1 Clinical Unit/kg/h of secretin for 150 min. CCK was added to the infusion after the first 75 min. Only one dose of CCK (0.75, 1.5, 3, 6, 16 24 Ivy dog U/kg/h) was given in any one experiment. Pancreatic juice was collected at one minute intervals for the first 15 min. at the beginning of the CCK infusion and at 15 min. intervals thereafter. CCK induced a biphasic pattern of pancreatic secretion: within 3 to 10 min. flow rate, protein, calcium, cyclic AMP and cyclic GMP output peaked in a dose dependent parallel manner. Then, the maximal flow remained constant while protein output reached a steady state; its value was fairly similar to that of the early peak for 0.75 to 6 U and for 16 and 24 U, the steady state value was lower than the first peak value. The pattern of calcium output was similar to that of protein output. The output of cyclic AMP and cyclic GMP increased until the end of the CCK infusion. When CCK (3 U/kg) was given as an intravenous bolus injection without any background of secretin, cyclic AMP, cyclic GMP and protein outputs peaked within 3 min. and then decreased. The results show that not only calcium and protein but also cyclic AMP and cyclic GMP secretion in the pancreatic juice depends on CCK. Key words: Dog, secretin, cholecystokinin, pancreatic juice: cyclic AMP, cyclic GMP, calcium, protein. PMID- 6254286 TI - [Direct solid-phase radioimmunoassay for the detection of Aujeszky's disease antibodies (author's transl)]. AB - A direct solid-phase radioimmunoassay (dRIA) was developed in order to demonstrate antibodies against Aujeszky's disease virus (ADV) in sera obtained from pigs and rabbits. In the presence of guinea-pig complement the above test is 160-fold to 1500-fold more sensitive than the neutralization test (NT) and 320 fold to 150 000-fold more sensitive than NT without complement. By means of dRIA ADV antibodies could be detected in swine sera obtained from an ADV-infected farm, which were found to be negative in the complement assisted NT. It is possible to test a single dilution of unknown serum by dRIA by comparing same with a standard curve and to make a statement regarding its ADV--specific binding capacity to 125I-labelled ADV antigen. The advantages of dRIA in comparison to the indirect RIA and the advantages and disadvantages with regard to ELISA were discussed. PMID- 6254288 TI - [Virological analyses of irradiated sewer sludge (author's transl)]. AB - The virus-inactivating effect of Co60 irradiation was verified by a field test in the sewer sludge irradiation plant at Geiselbullach near Munich. The following samples were tested: 16 waste water inlets 15 waste water outlets 32 fresh sludge samples 62 sewer sludge samples prior to irradiation 52 sewer sludge samples and 9 fresh sludge samples after irradiation. We supplemented these analyses by inoculating sewer sludge samples with polio inoculation virus type 1 before irradiation and by the admixing of virus-pure suspensions in MEM + 2 per cent fetal calf serum and virus sludge mixtures packed in plastic capsules with the material to be irradiated. After irradiation these capsules were picked up again and analyzed for their viral content. As test viruses we selected polio wild virus type 1, echovirus type 6, coxsackie virus B5, coxsackie virus A9 and adeno virus type 1. After the sludge samples had been sufficiently homogenized by an adequately long decaying period and provided they contained 3-per cent solid matter, we managed to obtain the same irradiation results in field tests, as with tests under laboratory conditions. For entero viruses the D-value (decimal reduction) was 300 to 400 krad, for adeno viruses it amounted to 700 krad. PMID- 6254289 TI - [Rational method for producing sera with high titers of virus-neutralizing antibodies. Part III]. AB - The effect of a number of nonspecific stimulators of immunogenesis (complete Freund's adjuvant, complete adjuvant prepared from Soviet made components, arlacel with vaseline oil, aluminium hydroxide) on the immune process has been studied. The highest titers of virus-neutralizing antibodies have been obtained with the use of complete Freund's adjuvant land complete adjuvant prepared from Soviet components (X=1 : 54040 and X=1 : 40960, respectively). PMID- 6254287 TI - [Aerosol vaccination of mice with inactivated influenza virus (author's transl)]. AB - NMRI mice were vaccinated by the aerosol technique, using the ethylethylenimine inactivated and polyethylenglycol concentrated virus strain A/PR/8/34 (HO/N1) with or without addition of Bordetella pertussis extract (BPE) as an adjuvant. The immune response of the vaccinated animals was controlled by challenge infection via aerosol technique and by examination of HAI antibodies in the serum and in the washings of lungs. After a single aerosol vaccination a weak protection was observed only, if the vaccines contained BPE. But a second immunization with a vaccine containing BPE induced a high degree of immunity, even if a reduced amount of antigen was used for booster vaccination. After three aerosol vaccine doses in two-weeks intervals, however, we were unable to infect the immunized animals even with largest amounts of challenge virus (approximately 50 000 LD50). The addition of BPE as an adjuvant induced a significantly better protection and resulted in much higher titres of HAI antibodies in the serum and in the respiratory tract compared to mice vaccinated by the same procedure but without BPE. PMID- 6254290 TI - [Treatment of rapid nodding "salaam" spasms in childhood]. AB - The paper deals with the etiology and epidemiology of "blitz" nodding spasms. The course of the disease was followed in 70 children who received various kinds of therapy within 1965 to 1976. Apparent prevalence of boys, role of genetic factors and the decisive importance of perinatal damages are noted. Even in the initial stage of the disease most children showed apparent signs of psychomotor retardation because of an early damage to the brain. The earliest time of the disease onset was the third week of life. An electroencephalographic examination showed a prevalence of type I (generalized) hypsarrhythmia. Treatment with ACTH and nitrazepam (radedorm) and in some cases also with apidan, lepsiral and chlopazepam was given. Frequent revision of the treatment schemes and combined treatment were found necessary. Only 5 of the 70 children developed in accordance with age; 18 children died of intercurrent infections at an age of under 5 years. Modern drugs (nitrazepam, dipromyl acetate, chlonazepam) did not improve the disease prognosis and could not replace completely the hormonal therapy. PMID- 6254291 TI - [Alcoholic polyneuropathies (review of the literature)]. PMID- 6254292 TI - [Status of blood coagulation and various background endocrine indices in patients with basal meningiomas during pre- and postoperative periods]. AB - The condition of blood coagulation activity and the indices of the endocrine background were studied in patients with tumors of prevalently basal localization which caused a direct effect on the central regulating centers. Thirty patients with basal and medially located meningiomas were examined in the pre- and postoperative periods. Before the operation most patients had clinical signs of endocrine-metabolic disorders, often in the presence of an increased content of ACTH and cortisol in the blood. Blood coagulation was disturbed in the majority of patients, mainly due to increased activity of the blood coagulation system. In the postoperative period, blood coagulation activity in 24 of 30 patients was increased or showed a tendency to increase in the presence of elevated blood ACTH content while processes of fibrinolysis were inhibited, which substantiates the necessity for anticoagulant therapy when large doses of glucocorticoids are used. PMID- 6254293 TI - Coordination of Gly-Tyr x Pd(II) complex to GMP nucleotide. AB - Coordination of the glycyl-L-tyrosinate x Pd(II) complex to guanosine-5' monophosphate (GMP) has been studied using 1H, 13CV NMR and electron spectra methods. Two kinds of monomeric ternary complexes were found in aqueous solutions: Gly-Tyr x Pd(II)-N7(GMP) complex (Pd-N7) at pH range 3 - 9 and Gly-Tyr x Pd(II)--N1(GMP) complex (Pd-N1) at pH above 5.2. The influence of the aromatic ring of tyrosine upon the chemical shifts for the -N7 bonded nucleotide molecule suggest that the plane of the purine ring and that of the Gly-Tyr x Pd(II) complex are almost perpendicular to each other. PMID- 6254294 TI - Characterization of [3H]dihydroergocryptine binding sites in brown adipose tissue. Evidence for the presence of alpha-adrenergic receptors. PMID- 6254295 TI - The paradox of sarcomas. PMID- 6254296 TI - Configuration of surfaces of human cancer cells obtained by fine needle aspiration biopsy: a comparative light microscopic and scanning electron microscopic study. AB - The surface configuration of human cancer cells removed from their natural setting by fine needle aspiration biopsies was studied by scanning electron microscopy. Cells from several carcinomas of the breast, malignant melanomas, oat cell carcinomas and a malignant lymphoma were the subject of this study. Only viable cells, identified by light microscopy prior to scanning, were selected for study. Contrary to prior observations on cancer cells in effusions, the surface configuration of human cancer cells obtained directly from tissues is variable and may depend significantly on the histologic patterns. PMID- 6254297 TI - Identification of papillary hidradenoma of the vulva by imprint cytology. PMID- 6254298 TI - Calcium and phosphate metabolism in acromegaly. AB - A study of 28 consecutively admitted patients with active acromegaly revealed the following results with regards to calcium and phosphate metabolism. When compared with controls, there was an increase in serum calcium levels corrected for total protein, urinary calcium was increased, but the tubular re-absorption of calcium was normal. There was a negative correlation between the urinary cAMP and calcium excretion indicating that hyperabsorption of calcium from the gut is the cause of the increased urinary calcium excretion. Serum phosphate values were increased in acromegalics and correlated well with TmP/GFR which was also increased. Immunoreactive parathyroid hormone (PTH) was increased in 5 patients, three of whom had hypercalcaemia. In the remaining patients the PTH values were scattered within the normal range. The urinary cAMP/creatinine ratio was increased in acromegalics, but most of this difference was abolished when urinary cAMP was expressed relative to 100 ml of glomerulus filtrate. It is concluded that parathyroid hyperactivity is a feature of acromegaly. PMID- 6254299 TI - Urinary 3',5'-cyclic adenosine monophosphate in relation to serum and urinary calcium in acromegaly and primary hyperparathyroidism. AB - A comparison of the interrelations between serum and urinary calcium values and the urinary excretion of cAMP in acromegaly (No. of subjects: 26), patients with primary hyperparathyroidism (n = 18) and control subjects (n = 42) is presented. The cAMP excretion was greatest in primary hyperparathyroidism, but acromegalics also exhibited higher values for this parameter than controls. A positive correlation was found between serum calcium values and cAMP in primary hyperparathyroidism, while acromegalics showed no correlation between these parameters. In controls there was a negative correlation between serum calcium and cAMP. Serum calcium levels corrected for variations in total protein concentrations were elevated both in acromegaly and primary hyperparathyroidism, mostly in the latter. Acromegalics and patients with primary hyperparathyroidism exhibited an increase in 24 h calcium excretion. While there was a negative relationship between urinary calcium excretion and cAMP in acromegaly, a positive correlation between these parameters as found in primary hyperparathyroidism. Controls showed a negative correlation between urinary calcium values and cAMP. It is concluded that the role of the parathyroids in the regulation of calcium metabolism in acromegaly is different from that of both normal controls and primary hyperparathyroidism. It is postulated that an active form of Vitamin D plays a major role in the regulation of calcium metabolism in acromegaly. PMID- 6254300 TI - Hypothalamic-pituitary-testicular function in rats after supraphysiological doses of a highly active LRH analogue (buserelin). PMID- 6254301 TI - Familial Cushing's syndrome with primary adrenocortical microadenomatosis (primary adrenocortical nodular dysplasia). AB - Cushing's syndrome was found in 2 of 4 siblings all of which also had other malformations. After bilateral adrenalectomy no hyperpigmentation was noted. Morphologically the adrenals of both siblings with Cushing's syndrome showed the typical lesions of the so-called microadenomatosis or primary adrenocortical nodular dysplasia with foci of eosinophilic giant cells. This is a new form of Cushing's syndrome due to an inborn error of the adrenals and no hypothalamic pituitary dysfunction. PMID- 6254302 TI - Biosynthetic ad morphological evidence for inhibition of aldosterone production following administration of ACTH to sheep. AB - The effect of ACTH administration for 1-5 days on the morphology and steroidogenic capability of sheep adrenal tissue has been examined. During this period of treatment there was a gradual decline in the in vitro conversion of 3H labelled precursors to products of solely zona glomerulosa origin (aldosterone and 18-hydroxycorticosterone) while conversion to products of zona fasciculata origin (17-hydroxyprogesterone, 11-deoxycortisol and cortisol) was stimulated throughout. Conversion to DOC, 18-hydroxydeoxycorticosterone and corticosterone (steroids produced by both the zona glomerulosa and the zona fasciculata) declined after initial stimulation. Within 2--3 days of the commencement of treatment, the zona glomerulosa showed a progressive decrease in cell number associated with disruption of cords and cell separation. Ultrastructurally, it was found that typical zona glomerulosa cells had almost disappeared. The majority of residual cells in this area had a structure intermediate between zona glomerulosa and zona fasciculata cells. The similarity in time-course of the alterations in both the morphological and biosynthetic characteristics suggests that the decline in aldosterone output caused by ACTH administration to sheep results from the loss of adrenal zona glomerulosa cells, predominantly due to selective cellular degeneration. PMID- 6254303 TI - Stimulation of rat ovarian ornithine decarboxylase in vitro by hCG, amino acids and bovine serum albumin. AB - Rat ovarian ornithine decarboxylase activity could be stimulated in vitro by a variety of factors, which apparently have different modes of action. Ovarian cells prepared from pre-pubertal rats by collagenase dispersion exhibited a low but detectable ornithine decarboxylase activity after a 6-h incubation in a defined medium. The enzyme activity as markedly enhanced in vitro by hCG, which also produced increased accumulation of cyclic AMP and stimulated the secretion of progesterone. In addition to the gonadotrophin, ovarian ornithine decarboxylase activity was strikingly stimulated by some non-essential amino acids, and especially by bovine serum albumin. While markedly enhancing ornithine decarboxylase activity, none of the latter additions increased the accumulation of cyclic AMP or enhanced the secretion of progesterone. Bovine serum albumin enhanced powerfully ornithine decarboxylase activity in vitro at very small concentrations (from 0.75 muM). The half-life of the enzyme remained unchanged (26-28 min) upon stimulation indicating that the stimulation mechanism did not involve any stabilization of the enzyme. PMID- 6254305 TI - A pituitary tumour with possible ACTH and TSH hypersecretion in a patient with Addison's disease and primary hypothyroidism. AB - A patient with Addison's disease, who was inadequately substituted with corticosteroids for twenty-five years, developed a pituitary tumour. The diagnosis of autoimmune thryroiditis with asymptomatic hypothyroidism was also made. ACTH and TSH plasma values were abnormally elevated. The ACTH secretion was suppressed by cortisone administered perorally. It seems possible that the pituitary enlargement is due to prolonged insufficient adrenocortical replacement therapy. The differential diagnosis and possible pathogenetic factors are discussed. PMID- 6254304 TI - Marathon run: effects on blood cortisol -- ACTH, iodothyronines -- TSH and vasopressin. AB - Blood cortisol, ACTH, thyroxine, triiodothyronine, reverse triiodothyronine, thyroid stimulating hormone (TSH) and vasopressin concentrations were determined in 9 runners (29-56 years old) and one 80 year old man taking part in a non competitive Marathon in Athens, Greece on October 1976. After the run the mean concentrations of cortisol, ACTH and vasopressin showed a significant rise. The thyroid function variables and TSH did not differ from the control values. There was a significant correlation between the cortisol and ACTH levels after the race and also between their increments from the corresponding base values. A significant correlation was found between the physical fitness (as measured by indirect determination of VO2max) and the post-race cortisol levels. One of the well trained runners with a fairly good running time had the highest post-race values for 6 of 7 hormones studied. PMID- 6254306 TI - Gonadal dysfunction in adult men with congenital adrenal hyperplasia. AB - Two adult males are described with congenital adrenal hyperplasia (21-hydroxylase deficiency). Patient 1 was receiving therapy with cortisone acetate and presented with clinical features of glucocorticoid excess and uncontrolled adrenal androgen activity. It was established that the short-acting steroid which the patient was receiving was cleared so rapidly that endogenous ACTH secretion was not inhibited. Patient 2 presented with enlarged and painful testes in association with poor compliance with corticosteroid therapy. The histologic picture of the testis was compatible with 'Leydig cell hyperplasia'. However, successful response to dexamethasone therapy suggests that the testes harboured an adrenal rest. These observations highlight the need for careful follow-up and treatment of adult male patients with congenital adrenal hyperplasia. PMID- 6254307 TI - The effect of chronic low-dose infusion of ACTH (1-24) on renin, renin-substrate, aldosterone and other corticosteroids in sodium replete and deplete man. PMID- 6254308 TI - Extracellular cyclic AMP levels in osteomalacia. PMID- 6254309 TI - Cyclic AMP release from normal human thyroid slices in response to thyrotrophin. AB - Slice preparations of normal human thyroid tissue were incubated in vitro with TSH. The cyclic AMP contents of slices were determined at intervals up to 120 min, and cyclic AMP in the incubation medium was also estimated for each incubation period. Slice cyclic AMP levels were related both to incubation time and TSH dose. In response to 10 mU TSH/ml, slice cyclic AMP levels were maximal within 60 min, and were not significantly changed at 120 min. Cyclic AMP was detectable in the medium within 10 min of slice exposure to TSH, and increased throughout the initial 60 min of incubation. Cyclic AMP release during this period was dependent on both TSH dose and incubation time. Between 60-120 min, however, cyclic AMP release partially lost its TSH dose-dependency, and 0.5-5.0 mU TSH/ml were equipotent with respect to the final medium cyclic AMP level attained. Slices incubated without TSH released only small amounts of cyclic AMP, and maximal levels were attained within 20 min. In contrast to the adenylate cyclase response of thyroid membrane preparations, which was stimulated by NaF, suggesting that cyclic AMP release was not a result of the stimulation of damaged cells. These findings demonstrate the importance of cyclic AMP release from human thyroid slices, following in vitro exposure to TSH, and suggest that, after incubation periods such as are used for the functional biodetection of thyroid stimulators, the magnitude of cyclic AMP release may be of quantitative significance. PMID- 6254310 TI - Uptake of L-triiodothyronine into human cultured lymphocytes. AB - The cellular uptake of [125I]L-triiodothyronine and its analogues was investigated in IM-9 human cultured lymphocytes. Uptake of L-triiodothyronine was one half maximal within 15 min of incubation and maximal within 45 min. The efflux of the hormone followed first order kinetics having a one half time of 15 min. Treating the cells with either the mitochondrial inhibitors antimycin-A and potassium cyanide, or lowering the incubation temperature to 12 degrees C, markedly reduced uptake. The uptake of [125I]L-triiodothyronine was saturable having an affinity constant (Kd) of 110 nM. When thyroid hormone analogues were studied D-triiodothyronine and triiodothyroacetic acid (analogues known to bind avidly to nuclear receptors) competed only weakly with [125I]L-triiodothyronine for uptake. These findings indicated the importance of the intact L-alanine side chain of the thyroid hormone molecule for its uptake into lymphocytes. Other studies, with cultured rat hepatocytes, demonstrated a similar saturable uptake system for [125I]L-triiodothyronine. These studies suggest, therefore, that the uptake of thyroid hormones and their analogues into cells may be an important step in the biological actions of these hormones. PMID- 6254311 TI - Study of the role of adrenocortical cyclic AMP and cyclic GMP on ascorbic acid depletion and corticosteroidogenesis by analysis of circadian rhythms. PMID- 6254312 TI - Desensitization of the cyclic AMP system in rat corpora lutea. Comparison between the effects of hCG and LH. AB - The changes in hormonal responsiveness of corpora lutea produced by a single injection of hCG or ovine LH were studied in PMSG-treated immature rats with well characterized corpora lutea of different ages. The hormonal response was measured as LH-stimulated accumulation of cyclic AMP in isolated, whole corpora lutea and, in some experiments, as LH stimulated luteal adenylate cyclase activity. Injection of hCG produced a complete desensitization (refractoriness) of very long duration (4-5 days) as has earlier been found in rats with heavily luteinized ovaries, while the injection of LH in equivalent doses, produced only a partial desensitization of much shorter duration (12-48 h). Morphological observations, after injection of trypan blue to a small number of the rats, showed that follicular growth, ovulation and formation of new corpora lutea could occur after both hCG and LH. The possibility that the corpora lutea which started to respond to LH stimulation 5-7 days after the hCG injection were not the ones originally desensitized by hCG but new corpora lutea, is discussed. The very rapid recovery of the LH sensitivity after desensitization with LH, can, however, not be explained in the same way. It represents a true reversal to the 'normal' hormonal sensitivity of the cells originally desensitized. The marked difference between hCG and LH in these desensitizing experiments is discussed in relation to earlier known differences between these two gonadotrophins, e.g. in binding properties to ovarian receptors and in rate of metabolism in the body. PMID- 6254313 TI - Cyclic AMP phosphodiesterases of the rat ovary. Oestrous cycle dependent activity change of high affinity form. AB - In the rat ovary, from prenatal to adult stages, two electrophoretically distinct forms of cyclic AMP phosphodiesterase (E.C.: 3.1.4.17) occur. These forms were analysed for their affinity towards cAMP in both crude and partially purified preparations. Whereas the slow electrophoretic form, which has a low affinity towards cAMP, shows a linear Lineweaver-Burk plot, the fast electromorph exhibits anomalous kinetic behaviour in that cAMP affinity appears to increase with decreasing cAMP-concentration. This form shows dramatic alteration of maximum velocity during the oestrous cycle, attaining maximum activity at metoestrus. This rise of activity is sensitive to inhibition of protein synthesis. PMID- 6254314 TI - Effects of insulin treatment on the activities of phosphoprotein phosphatase and its inhibitors. AB - An increase in glycogen synthase phosphatase (phosphoprotein phosphatase) activity was observed in the rat skeletal muscle extract following insulin administration. The phosphoprotein phosphatase activity present in the muscle extract from insulin treated rats was observed to remain elevated after the extract had been subjected to a molecular sieve chromatography. These results indicate that the stimulatory effects of insulin is due to modification of phosphatase itself or some macromolecular weight modifiers. The heat-stable protein inhibitors of the phosphoprotein phosphatase were isolated from skeletal muscle of insulin treated and control rats and their inhibitory potencies were compared over a wide range of protein concentrations. The inhibitory potency in the insulin treated rat skeletal muscle was found to be significantly less than that in the control muscle. Since type-1 inhibitor is well-known to be active only after being phosphorylated by cyclic AMP-dependent protein kinase, we suggest that the observed change in phosphoprotein phosphatase inhibitor potency is most likely mediated by an alteration in the phosphorylation state of type-1 inhibitor. PMID- 6254315 TI - Use of arylsulphonic acids for histochemical demonstration of cholesterol and its esters. AB - A histochemical technique is being described using for the demonstration of cholesterol and its esters a reagent composed of sulphuric acid and 2,5 dimethylbenzene sulphonic acid or p-toluene sulphonic acid dissolved in glacial acetic acid. The results of this method have been compared with other methods for cholesterol identification and verified by extraction and chromatographic techniques. The main advantage of the presented procedure is a better preservation of sections, due to the use of smaller amounts of sulphuric acid, permitting thus a more exact histological localization of cholesterol. PMID- 6254316 TI - A review of skeletal muscle contraction and neuromuscular function. PMID- 6254317 TI - Effect of an anion transport inhibitor on blood-brain barrier lesions during acute hypertension. Possible prevention of transendothelial vesicular transport. AB - Opening of the blood-brain barrier (BBB) by a hypertensive insult comprises the formation of endothelial micropinocytosis. Constricted vessels are less vulnerable to the insult. In the present study SITS (4-acetamido-4'-isothiocyano stilbene-2,2'-disulfonic acid disodium) was shown to prevent leakage across the BBB into the brain parenchyma following a hypertensive insult induced by a local increase of the intraluminal pressure in anesthetized rats and by i.v. administration of adrenaline or bicuculline in conscious unrestrained animals. Since SITS induced an increase in cerebral blood flow the protection cannot be explained by a constrictory action on the cerebral vessels. SITS is a drug with complex action on the cell membrane including an inhibitory effect on anion transport mechanisms and on some c-AMP mediated processes. It is possible that the protection of BBB observed in the present study is connected to a reduction of c-AMP but membrane stabilizing effect can at present not be excluded. PMID- 6254318 TI - Intraneuronal polyglucosan storage restricted to the lateral pallidum (Bielschowsky bodies). A golgi, light, and electron microscopic study. PMID- 6254319 TI - Ultrastructural study of globular inclusions in human skeletal muscle mitochondria. AB - Limb muscle biopsies from a patient with Luft's disease and a patient with a slowly progressive neuromuscular disorder since infancy revealed by conventional electron microscopy the presence of globular inclusions in the mitochondria as one of the most prominent morphological findings. Electron cytochemical studies on fresh tissue blocks showed no cytochrome c oxidase activity within the globular inclusions. The study of strontium uptake supported by either NAD and flavo-protein linked substrates in freshly isolated mitochondria fractions showed no electron-dense needles within the globular inclusions. Attempts to remove the inclusions with pepsin and with pronase on ultrathin sections failed but they were partially and totally removed by treatment of the sections with hydrogen peroxide. Freeze fracture studies showed the globular inclusions consisted of amorphous and lamellar material. The results suggest that the globular inclusions in muscle mitochondria may consist primarily of lipid. PMID- 6254320 TI - Brain aging in normotensive and hypertensive strains of rats. II. Ultrastructural changes in neurons and glia. AB - A variety of age-related changes occur in the structure of neurons in the cerebral cortex of Wistar-Kyoto and spontaneously hypertensive rats. The most marked alteration associated with increasing age was the deposition of lipofuscin pigment, primarily at the bases of apical dendrites of pyramidal neurons. While no strain-related differences in the amount of lipofuscin pigment were observed in the youngest (3 months) and in the aged (22-27 months) groups of rats, it appeared that hypertensive rats had larger pigment deposits at 12 months of age. At the ultrastructural level, neurons of the aged brains exhibited numerous nuclear invaginations and filamentous nuclear inclusions, increased amounts of Golgi complex and two types of cytoplasmic inclusions. The number of degenerative structures in the neuropil (membranous whorls, dystrophic axons and alterations in myelin sheaths) was also apparently increased in the aged brains. Neurofibrillary tangles were observed in dendritic processes of a 27-month-old Wistar-Kyoto rat. Glial cells accumulated distinctive pigment granules by which the three types of glia could be identified. PMID- 6254321 TI - Intracytoplasmic neuronal inclusions in the human thalamus. Light-microscopic, histochemical, and ultrastructural observations. AB - Intracytoplasmic eosinophilic inclusions were found by light microscopy in the thalamic neurons of 35 consecutive normal adult brains and in a case of myotonic dystrophy, but not in six newborn children, including one with myotonic dystrophy. Histochemical tests suggested a protein composition. Ultrastructurally, the inclusions were composed of stacks of parallel alternating dark and light rectilinear profiles not surrounded by a limiting membrane. Such inclusions are a virtually constant finding in the adult human thalamus and probably represent sites of neuronal protein storage. PMID- 6254322 TI - Elevated stapedius reflex threshold and pathologic reflex decay. Clinical occurrence and significance. PMID- 6254323 TI - Audiologic test results in 96 patients with tumours affecting the eighth nerve. A clinical study with emphasis on the early audiological diagnosis. PMID- 6254324 TI - Breast carcinoma. Aspects of early stages, progression and related problems. PMID- 6254325 TI - Effect of the antitumour agent 5-(3,3-dimethyl-1-triazeno imidazole-4-carboxamide (DTIC) on cyclic AMP levels in intact MH1C1 hepatoma cells. AB - Addition of the cytostatic agent 5-(3,3-dimethyl-1-triazeno)-imidazole carboxamide (DTIC, dacarbazin) to MH1C1 hepatoma cells, alone or in combination with adrenaline, was shown to elevate intracellular cyclic AMP. The cyclic AMP level was increased from basal values of about 0.40 to about 0.75 pmol/mg protein 10 min. after DTIC addition. Accumulation of cyclic AMP in response to a supramaximal concentration of adrenaline is amplified in a dose-dependent way by 0.1-2 mM DTIC. The effect is apparently due to inhibition of cyclic AMP breakdown, since DTIC inhibits the low-Km form of the cyclic AMP phosphodiesterase without significantly affecting the adenylate cyclase activity of MH1C1 homogenates. PMID- 6254326 TI - Effects of ACTH on the synthesis and metabolism of prostaglandin in rat kidney. AB - Prostaglandin (PG) synthetase activity of rat kidney medulla microsomal fraction was determined in vitro using I-14C-arachidonic acid as substrate. Natural ACTH resulted in a dose dependent suppression of PGE2 formation in vitro. The biosynthesis of PGE2 alpha was enhanced in the presence of ACTH (cortrophin). ACTH4--10 (1-Phe7 or d-Phe7) resulted in decreased PGE2 synthesis. The ratio of PGF2 alpha/PGE2 increased in proportion to the concentration of natural ACTH. The increase in the ratio of PG-s was more pronounced when ACTH4--10 fragments were applied. Natural ACTH in a dose dependent manner inhibited the prostaglandin dehydrogenase activity of kidney cytosol fraction in vitro. Prostaglandin inactivation was suppressed only by high doses of ACTH4--10 (d-Phe7). The data indicate that the natural ACTH and ACTH4--10 fragments might have a physiological role in the regulation of the prostaglandin system of a non-steroidogenic tissue. PMID- 6254327 TI - Reconstitution of the Na+, K+-transport system in artificial membranes. AB - (1) Purified renal Na+, K+-ATPase was incorporated into phosphatidylcholine liposomes by using the cholate-dialysis procedure. The passive permeability of the liposomes for Na+ and K+ was determined on 22Na and 86Rb equilibration curves. The rate constant for passive Na-flux was 0.014 min-1 and for K(86Rb) flux 0.013 min-1. Active transport rates of Na+ and K+ were determined after addition of 3 mM ATP to the liposomes. (2) A micromethod for continuously measuring the ADP production associated with active transport is described. Using this technique, initial velocities of ATP hydrolysis were measured in parallel with Na+-transport and K+-transport. When the Na+-concentration in the incubation medium is increased, the initial velocity of all three processes increase concomitantly. At high turnover, the stoichiometry of coupled Na+, K+-transport catalyzed by the purified reconstituted pump is 2.2Na+: 1K+:1ATP. (3) When the pump has exhausted the vesicular K+-pool, coupled NA+, K+-transport ceases. The pump then carries Na+ uphill without K+-antiport. The Na+: ATP ratio of uncoupled Na+-transport is close to 1:1. PMID- 6254328 TI - Modulation of alamethicin-induced conductance by membrane composition. AB - The effect of cholesterol on the opening and closing of the alamethicin-channel was studied varying the cholesterol content of glycerolmonooleate membranes. Increasing the cholesterol mole fraction in the membrane shifted the log of the steady-state conductance-voltage curve to the right along the voltage axis. The shift was found to be 80-100 mV when the cholesterol mole fraction was increased from 0 to 0.5. The kinetic for the approach to steady-state conductance during voltage clamp was also studied in membranes under these conditions. At all the different cholesterol contents the on kinetic is well described by a single exponential. The off kinetic, on the other hand, is described by a double exponential time course. At the same voltage the time constant describing the on current relaxation is the same as the one found for the slow relaxation present in the off relaxation. Increasing the membrane cholesterol content increases the magnitude of the time constant describing the fast and slow process by several orders of magnitude. Cholesterol also increases the voltage dependence of the slow time constant. The effect of cholesterol on the steady-state conductance can be explained, but not in a unique way, by an increase in the membrane dipole potential. Phenomenological comparison of the fast and slow kinetic processes seen in multi-channel membranes with single channel characteristics indicates that: (i) cholesterol increases the mean life of the single channel and (ii) cholesterol increases the mean life of the different conductance levels. PMID- 6254330 TI - On bilayers and biological membranes. PMID- 6254329 TI - Effects of lipid structure on the kinetics of carrier-mediated ion transport. AB - The mechanism of alkali-ion transport mediated by valinomycin (or similar macrocyclic carriers) may be studied using artificial planar bilayer membranes. The rate constants of the single transport steps (association and dissociation of the ion-carrier complex, translocation of free and complexed carrier) can be determined from electrical relaxation experiments. The turnover number of valinomycin which may be calculated from the rate constants is found to be 10(4) 10(5) s-1. Carriers of the valnomycin-type offer the possibility of studying the relationship between membrane structure and transport kinetics. Increasing the chain-length of the lipid strongly reduces the translocation rate constants of the free and the loaded carrier, and also (in the case of lecithin membranes) the association rate constant. Increasing the number of double bonds in the fatty acid residue of the lipid leads to an inrease of the translocation rate constants. These effects are discussed in terms of microviscosity of the membrane. Addition of cholesterol to monoglyceride membranes seems to affect both the microviscosity and the dipolar potential at the membrane-solution interface. PMID- 6254331 TI - Depth dose data for 4 MeV linear accelerators with lead or uranium field flatteners. AB - Per cent depth dose data for a few selected depths for 4 MV roentgen rays from Varian Clinac-4 linear accelerators equipped with lead or uranium field flatteners are presented and compared with published data. A difference by as much as 12 per cent was found. PMID- 6254333 TI - Microdosimetry. I. Use of secondary electron emission. AB - The potential of secondary electron emission as a basis for microdosimetric analysis is explored. Secondary electron emission phenomena are compared with gaseous ionisation and a brief review of work on the stochastic nature of secondary emission is presented. Input data are selected and calculations undertaken to obtain lineal energy spectra. The frequency and dose mean of lineal energy obtained from these calculations in various volumes are compared with results obtained with proportional counters. Some biologic applications of this approach to microdosimetry are discussed. PMID- 6254332 TI - Dual photon absorptiometry in lumbar vertebrae. Evaluation of the baseline error. AB - In connection with determination of the bone mineral content in the third lumbar vertebra by dual photon absorptiometry, the fat in the adipose capsules of the kidneys is assumed to cause erroneous positioning of the baseline, leading to overestimation of the bone mineral content. The bone mineral content in L3 was measured in situ (BMC1) and vitro (BMC2) in 14 cadavers. The difference between BMC1 and BMC2 was significantly greater than zero, the median value being 0.32 g/cm at the confidence level of 94.4 per cent. It is concluded that at correlation between bone mineral content and compressive strength in vitro, the in vivo strength is overestimated by about 250 N. PMID- 6254334 TI - Significance of quantum fluctuations in roentgen imaging. AB - Quantum fluctuations in the roentgen radiation relief are analysed mathematically. The intrinsic signal-to-noise ratio of the radiation relief for a given object contrast is proportional to the square root of the number of photons contributing to the image of a characteristic detail in the object. In the presence of secondary radiation the signal-to-noise ratio is impaired, since the fluctuations of secondary radiation increase the noise of the radiation relief. By efficient secondary screening, the quality of the relief can be partially recovered. With a dynamically limited recording device, i.e. a film-screen combination, increased detection speed in conjunction with improved secondary screening will either result in unchanged image quality with the gain of an object-dose reduction or provide improved imaging at an unchanged dose value. As regards the relation between contrast resolution and spatial resolution, the dose required to barely demonstrate an object detail of given geometry and composition is found to vary inversely with the fourth power of the linear size of the detail. It is also concluded that recording and secondary-screening devices should always be considered together as far as recording quality is concerned. PMID- 6254336 TI - Effect of different 90Sr doses on the microscopic structure of foetal mouse ovaries. AB - Pregnant CBA-mice were injected with different doses of 90Sr on the 19th day post coitum. The doses ranged between 11.1 and 370 kBq (0.3-10.0 muCi) per animal. The ovaries of the in utero treated females were analysed when the animals were 28, 56 or 84 days old, respectively. The effect of the nuclide was expressed as a reduction of the number (frequency) of cells in different stages of ovarian development in a comparison between 90Sr treated animals and untreated controls. The injury (reduced number of cells) was strongly correlated to log dose. The most radiation sensitive stage (the naked oocytes) was clearly affected even at the lowest dose level. The different ovarian 90Y/90Sr ratios in litters and their mothers are discussed. PMID- 6254335 TI - Natural killer activity in peripheral lymphocyte population following local radiation therapy. AB - The natural killer (NK) activity of peripheral lymphocytes against 51Cr-labelled Chang or K562 cells was tested using a 4 h release assay before and after postoperative radiation therapy for mammary carcinoma. NK activity against K562 was significantly reduced at completion of therapy (a total target dose of 45.0 Gy) and restituted 3 to 4 months later. NK activity against Change cells exhibited a slight but non-significant decline at completion of therapy followed by an overshoot 3 to 4 months later. The frequency of Fc-IgG receptor bearing lymphocytes was decreased at completion of therapy and largely restored after 3 to 4 months. PMID- 6254337 TI - Chromosome counts of 90Sr-induced osteosarcomas in mice. II. Variation of the chromosome counts of slow and fast growing tumours in hyper- and nonhyperimmunized hosts. AB - Highly inbred CBA mice were used. The registration of chromosome abnormalities was limited to numerical deviations and the occurrence of metacentric chromosomes. By separate serial transplantation from a 90Sr-induced osteosarcoma two parallel transfer series (B and b) were established. From these series transplantation was also performed to hyperimmunized hosts B (Hi) and b (Hi). Besides differences in mean outgrowth period between B-and b-generations, a variation in chromosome pattern was observed. However, this variation should not be evaluated as a typical chromosomal progression of fast and slow growing tumour series. PMID- 6254338 TI - Mitomycin C in advanced gallbladder carcinoma. AB - Seven patients with advanced gallbladder carcinoma were given intraarterial infusions of 10 to 15 mg mitomycin C with 10 to 24 days' interval, 3 received intravenous infusion (10 mg/m2) with median 3 weeks' interval. Stationary disease was obtained in 4 patients, progressive disease in 4, and treatment failures in 2. The median survival after mitomycin C treatment was 4 months (range 1-23 +). Irreversible thrombocytopenia occurred in 2 patients and a severe gastrointestinal bleeding episode in one. PMID- 6254339 TI - Pentagastrin, calcium and whisky stimulated serum calcitonin in medullary carcinoma of the thyroid. AB - The efficiency of pentagastrin, calcium and whisky in raising serum immunoreactive calcitonin (S-iCT) concentrations was analysed in 6 patients with medullary carcinoma of the thyroid and in 8 healthy controls. All 6 patients responded to pentagastrin with a significant increase in S-iCT, 5 responded to calcium and only 3 to whisky. In the 8 controls no or only a modest increase in S iCT occurred following pentagastrin, calcium and whisky with no difference between the three. It is concluded that pentagastrin is the most useful stimulative agent for ICT secretion in patients with C-cell neoplasms. In selected cases the additional use of calcium could be advantageous. PMID- 6254340 TI - Neutron radiation therapy of parotid gland tumors. AB - A retrospective analysis of 9 patients treated with cyclotron fast neurons for tumors arising from the parotid gland is presented. In 3 of 4 patients who survived longer than 2 years, significant normal tissue damage occurred within the treatment volume. Five patients treated with neutrons or surgery plus neutrons for primary tumors stage III did not have a better prognosis with regard to survival than a comparable group of patients treated with conventional methods (i.e. surgery, photons, or a combination thereof). These results appear to be similar to those obtained for parotid tumors treated with neutrons in the early 1940's by STONE. PMID- 6254341 TI - Effect of different radiation fractionation schedules on metastases from an oesophageal carcinoma. AB - Subcutaneous metastases from an oesophageal carcinoma were irradiated using different schedules. The results have to be evaluated with greatest caution but indicate that with the same CRE value, few fractions caused less skin reactions than several, and the size of the shoulder of the cell survival curve was of the order of 0.7 Gy. PMID- 6254342 TI - Osteosclerotic myeloma with polyneuropathy. AB - Five cases of histologically verified plasma cell myeloma in sclerotic skeletal foci and polyneuropathy are reported. Thirty similar cases were collected from the literature. They illustrate a special form of plasma cell neoplasia. The characteristic features are osteosclerosis, polyneuropathy resembling polyradiculitis, approximately normal hemoglobin concentration, bone marrow smears and ESR, low concentration of M-protein, and absence of Bence-Jones' proteinuria. Slow progesssion of the disease is a possible additional feature. It is hypothesized that autoimmune mechanisms are involved in the pathogenesis. This hypothesis is based on the observation of circulating immune complexes, positive Waaler's reaction and relative increase in the number of circulating B lymphocytes. PMID- 6254343 TI - Atrioventricular and intraventricular conduction in familial amyloidosis with polyneuropathy. AB - Atrioventricular and/or intraventricular conduction disturbances were found in 48 (67%) out of 71 patients with familial amyloidosis with polyneuropathy. Low voltage, often described in various forms of heart amyloidosis, was seen in one patient only. Myocardial infarction patterns, also often reported in heart amyloidosis, were not present in our patients. The prevalence of conduction disturbances increased with the duration of the disease. In 28 out of 47 patients from whom more than one ECG recording was available, a progression of conduction disturbances could be seen. Ten patients developed high-degree conduction disturbances and required permanent pacemaker treatment. PMID- 6254344 TI - The role of timing and magnitude of the vagal input in controlling the phrenic output in rabbits and baboons. AB - The effects of a short train of electrical impulses applied to the central stump of a cut vagus nerve at various moments of the central respiratory cycle were studied in 28 rabbits and 3 baboons. The animals were anaesthetized (halothane), vagotomized, paralyzed and artificially ventilated. Stimulation in inspiration elicited always an inhibitory effect (latency 8-9 ms) the magnitude of which increased towards the end of inspiration. The amplitude and duration of inhibition increased also with the frequency of impulses and/or the duration of the volley. Stimulation in expiration shortened this phase after latency being shorter towards the end of expiratory pause. It is suggested that excitation of thin myelinated vagal fibres has a facilitatory effect on the inhibitory response to information being conducted along thick myelinated fibres during inspiration. PMID- 6254345 TI - Subcortical connections of the prefrontal cortex in dogs: afferents to the orbital gyrus. AB - Afferent subcortical connections to the lateral prefrontal cortex (orbital gyrus) in the dog brain were investigated using the horseradish peroxidase retrograde transport method. It was shown that: (i) the main projection to this area derives from the ventral and intermediate regions of the mediodorsal nucleus of the thalamus, (ii) fairly rich projection arises from the midline, intralaminar as well as from ventromedial and lateroposterior thalamic nuclei, (iii) scanty extrathalamic projection to the lateral prefrontal area originates from several other structures like claustrum, hypothalamus, amygdala, ventral tegmental area, raphe nuclei and locus coeruleus. Distribution of labeled cells after particular injections showed that in the orbital gyrus two subdivisions may be distinguished: dorsal and ventral. It is suggested that the dorsal orbital subdivision in dog corresponds to the lateral prefrontal cortex in monkey. PMID- 6254346 TI - Glioblastoma multiforme of the cerebellum: description of three cases. AB - Only 43 cases of glioblastoma multiforme of the cerebellum have been reported in the literature. This report is based on the findings of 3 cerebellar glioblastomas in a review of 1,206 consecutive confirmed cases of glioblastoma operated on between 1947 and 1977 at the Istituto Neurologico of Milan, giving an incidence of 0.24%. Clinical features are similar to those of any other fast growing subtentorial tumour. Neuroradiological studies, including CAT, are of little help in predicting the exact nature of these tumours before surgery. A correct diagnosis can be reached only by microscopic examination. Histological patterns appear in no way to differ from those of cerebral glioblastoma. The biological behaviour of these tumours is in all respects identical to that of glioblastoma of cerebral hemispheres. PMID- 6254347 TI - Angioma of the jugular foramen. Case report. AB - We describe a patient with a neoplasm closely mimicking a glumous jugulare tumour with regard to both clinical and radiological presentation. The tumour was removed by the transmastoid route. Only after histological examination of the excised neoplasm could the diagnosis of angioma be made. No other case of this nature has been found in the literature. PMID- 6254348 TI - Normal and altered regional cerebral blood flow and solute movement across the cerebral capillary in rat. PMID- 6254349 TI - [Dosage of hormonal receptors for DHT in programming therapy for prostatic cancer]. PMID- 6254351 TI - Multivariate analysis of diet and serum lipids in normal men. AB - The relationships among intake of dietary fiber, fat, and serum lipids were examined in a population of 200 normal men. Univariate analyses indicated that men with lower serum cholesterol and triglyceride concentrations were consuming significantly more dietary fiber and proportionately fewer fat calories. However, higher fiber consumption was also associated with differences in relative body weight, fat intake, and cigarette smoking; the relationship of dietary fiber intake to serum lipids was largely mediated by those coexisting differences in other environmental variables. In contrast, the percentage of total calories consumed as fat was independently positively related to both serum cholesterol and triglyceride levels. PMID- 6254350 TI - Receptor mediated endocytosis. PMID- 6254352 TI - Physiological anemia of early development in the rat: characterization of the iron-responsive component. AB - The purpose of this study was to determine the circumstances under which the postnatal decline in concentration of hemoglobin in the rat can be modified by administration of iron. Base-line dietary regimens contained iron in what is considered an optimal amount, and additional iron-dextran administration to the dams had no significant influence on the concentration of hemoglobin in the pups. However additional iron when administered directly to the pups in the form of iron-dextran or heat-treated red cells did elevate the concentration of hemoglobin. The administration of iron was effective only before weaning at 21 days of age; subsequently, there was no significant effect. The age-related difference in hemoglobin-responsiveness corresponded to the effects of iron treatment on the concentration of serum iron. Between 11 and 21 days of age, serum iron values under base-line dietary conditions were low but they became increased in response to iron treatment. After 21 days of age, base-line serum iron values rose abruptly and were no longer substantially augmented by iron treatment. The findings suggest that a physiological period of low serum iron restricts the production of hemoglobin. During this period, administration of iron in greater than physiological doses was effective in raising the serum iron and the concentration of hemoglobin. PMID- 6254353 TI - Effectiveness of enteral and parenteral nutrition in the nutritional management of children with Wilms' tumors. AB - The effectiveness of enteral and parenteral feeding in supporting a satisfactory nutrition status and/or reversing protein-energy malnutrition was evaluated in nine children, ages 1 to 7 years (eight female), with Wilms' tumors. At the onset of treatment, eight patients received comprehensive enteral nutrition (CEN) which included intense nutritional counseling and oral supplements while one received total parenteral nutrition (TPN). Despite CEN, the initial, intense treatment period was associated with a decreased energy intake (64 +/- 27% Recommended Dietary Allowances), dramatic weight loss (22 +/- 7% by 26 +/- 17 days from the beginning of treatment), decreased skinfold thickness (< 10th percentile), and decreased albumin concentrations (< 3.2 g/dl). Four of those who initially received CEN subsequently required TPN. A total of five patients received TPN for a mean of 31 days (range 11 to 60); kcal averaged 105 +/- 9% Recommended Dietary Allowances during weight gain. At onset of TPN, the mean albumin, transferrin, total lymphocyte count were 3.02 +/- 0.45 g/dl, 155 +/- 40 mg/dl, and, 655 +/- 437/mm3, respectively; all children had abnormal anthropometric measurements and anergy to recall skin test antigens. TPN for 28 or more days supported weight gain (+ 2.44 kg), increased serum albumin (+ 0.58 +/- 0.47 g/dl) and transferrin (+ 76 +/- 34 mg/dl), and reversed anergy despite low total lymphocyte counts. During maintenance treatment, nutritional status was maintained or restored with CEN in the group who responded. These preliminary data document the severity of protein-energy malnutrition which accompanies initial, intense treatment of children with Wilms' tumors, the nutritional and immunological benefits of TPN during continuing intense treatment and the effectiveness of CEN in maintaining a satisfactory nutritional status during maintenance treatment. PMID- 6254354 TI - Mechanisms of thiamin deficiency in chronic alcoholism. AB - In the United States and other developed countries thiamin deficiency is often related to chronic alcoholism. A number of mechanisms may be involved in the pathogenesis of thiamin deficiency in the alcoholic population. An important cause is inadequate intake of thiamin. Moreover, there may be decreased converstion of thiamin to the active coenzyme, reduced hepatic storage of the vitamin in patients with fatty metamorphosis, ethanol inhibition of intestinal thiamin transport, and impaired thiamin absorption secondary to other states of nutritional deficiency. The present discussion focuses on the mechanism of ethanol-related thiamin malabsorption. Under normal conditions thiamin transport in animals and humans is biphasic. At low or physiological thiamin concentrations, transport is a saturable, carrier-mediated, active process; but at higher concentrations, the transport of thiamin is predominantly passive. Ethanol reduces the rate of intestinal absorption and the net transmural flux of thiamin. Furthermore, ethanol inhibits only the active and not the passive component of thiamin transport by impeding the cellular exit of thiamin across the basolateral or serosal membrane. The impairment of thiamin movement out of the enterocyte correlates with a fall in the activity of Na-K ATPase. Bound to the basolateral membrane, Na-K ATPase is believed to be involved in the kinetics of active transport. Ethanol also increases the fluidity of enterocyte brush border and basolateral membranes. Since ethanol increases membrane fluidity it is possible that tahe impairment of thiamin transport and the diminution of Na-K ATPase activity may be related, at least partly, to a physical perturbation of the enterocyte membrane. PMID- 6254356 TI - The role of narcotic antagonists in the rehabilitation of opiate addicts: a review of naltrexone. PMID- 6254355 TI - Plasma adrenocorticotrophic hormone in congenital adrenal hyperplasia. Importance in long-term management. AB - In a prospective study, assays of plasma adrenocorticotrophic hormone (ACTH) were compared with established criteria to evaluate the determination's usefulness in monitoring the control of congenital adrenal hyperplasia (CAH). In 22 infants and children with 21-hydroxylase deficiency, the plasma ACTH value correctly identified the status of control in 51 of 73 (70%) patient visits. Plasma ACTH concentrations were significantly higher in patients whose conditions were out of control when compared with patients whose conditions were under control, although there was an overlap between the two groups. Plasma ACTH concentrations were significantly higher in patients with sodium-losing CAH than in patients with non sodium-losing CAH. These findings support the concepts that patients with the sodium-losing condition have a more severe enzyme deficiency and that ACTH stimulation may be affected by sodium balance. Although plasma ACTH determinations are a useful adjunct in the long-term management of CAH, they cannot be relied on as the sole criterion of control. PMID- 6254357 TI - A case-control study of Hodgkin's disease in Brazil II. Seroepidemiologic studies in cases and family members. AB - A case-control study of antibody titers to the viral capsid antigen of Epstein Barr virus was carried out in 70 patients with Hodgkin's disease (HD) and in 92 siblings, 50 parents and 19 children of the HD patients, each paired with a control matched for age and sex. The geometric mean titer (GMT) of the HD patients was significantly greater than that of the controls (t69 = 6.30, p < 0.0005), and the proportion of HD cases with titers greater than or equal to 1:320 was significantly elevated (35.5% vs. 2.9%). No significant differences in GMTs were found when the HD patients were grouped by sex or by histologic subtype. An inverse correlation between age and titer was noted among HD patients but not among controls. The GMT of the 161 relatives of the HD cases was similar to that of their respective controls. Likewise, there was no significant elevation of the GMT of the subset consisting of family members of HD patients with high titers when compared to controls. However, when the GMT of the family members of HD patients with high titers was compared to that of the relatives of the HD patients with low titers, a significant difference was found (t159 = 2.54, p < 0.01). PMID- 6254358 TI - Epidemic outbreaks of adenovirus 7 with special reference to the pathogenicity of adenovirus genome type 7b. AB - Adenovirus type 7 (Ad 7) is the serotype among the 36 recognized adenovirus types which most frequently has been associated with severe illness. Three different epidemic patterns of Ad 7 infection can be distinguished: 1) the first appears during the winter among infants with median age below two years, has characteristic symptoms of high fever and pneumonia and an outcome that may be fatal: 2) the second appears in the fall among children with median age seven years, has characteristic symptoms of high fever, pneumonia, abdominal symptoms and meningism and an outcome that is favorable; 3) and the third has been seen as acute respiratory disease among military recruits. In the United States, the last mentioned outbreaks require prophylaxis in the form of a live enteric-coated vaccine. DNA restriction site mapping demonstrated the occurrence of three distinct viral entities of Ad 7, which have been designated Ad 7 prototype, Ad 7a (the vaccine strain) and the Ad 7b genome type. In the present study, 36 isolates obtained from outbreaks with the first and the second epidemic patterns were analyzed by restriction endonucleases Bam HI and Sma I. All were identified as the newly recognized Ad 7b genome type. It is concluded that this genome type is responsible for a large portion of the severe infections caused by Ad 7. The epidemic nature of Ad 7 and the severe illness noted among infants indicate that vaccination of institutionalized infants could be considered during years when Ad 7 epidemics appear. PMID- 6254359 TI - The role of the prostaglandin system in the regulation of renal function in normal women. AB - The role of prostaglandins in the regulation of renal function was studied in seven healthy female volunteers taking a constant metabolic diet containing 59 meq of sodium and about 50 meq of potassium daily. Each subject underwent two renal clearance studies, during which vasopressin (priming dose, 200 mU; "sustainer," 200 mU/hour at 1 ml/min) was infused intravenously. The first clearance study served as the control; indomethacin (2 mg/kg/day) was given for seven days before the second clearance study to inhibit prostaglandin synthesis. Food and fluid were withheld for 12 hours before the studies. Urine was collected through an indwelling bladder catheter at 30 minute intervals. Glomerular filtration rate was estimated from inulin clearance and renal blood flow from para-aminohippurate (PAH) clearance. Indomethacin was associated with a significant increase in maximal urinary osmolality from 826 +/- 47 mosmol/kg H2) to 920 +/- 32 mosmol/kg H2O (P < 0.01). Minimal "free water" clearance was -1.40 +/- 0.02 ml/min before and -1.63 +/- 0.04 ml/min (P < 0.01) after the administration of indomethacin. Indomethacin did not affect urine flow, urinary sodium or potassium excretion, glomerular filtration rate or renal plasma flow. In addition, indomethacin did not affect the urinary excretion of cyclic adenosine monophosphate (AMP). Plasma arginine-vasopressin, measured in two subjects by radioimmunoassay, did not change with blockade of prostaglandin synthesis. It appears that prostaglandins antagonize the hydro-osmotic effect of antidiuretic hormone by an intrarenal mechanism, independent of changes in renal hemodynamics or cation excretion. This mechanism is probably mediated by an alteration in the water permeability of the collecting ducts. Since urinary cyclic AMP did not change during blockade of prostaglandin synthesis, whereas urinary osmolality increased, a change of vasopressin-dependent cyclic AMP production in the kidney was probably not reflected in urinary cyclic AMP. PMID- 6254360 TI - Is the renin system necessary? AB - Numerous studies have been carried out to assess the role of the renin system in sustaining abnormally high blood pressure and in contributing to various other cardiovascular disorders such as congestive heart failure, ascites, and shock. The clinical use of potent and specific inhibitors of the renin-angiotensin system has produced important application in the treatment of high blood pressure, severe congestive cardiac failure and experimental hemorrhagic shock. Only in the state of considerable sodium depletion does blockade of the renin system produce any untoward effect, i.e. hypotension. These results are very similar to those obtained previously in patients with bilateral nephrectomy. They raise the question whether under conditions of our present salt-eating habits the renin system is really necessary. PMID- 6254361 TI - Suppression of human chorionic gonadotropin by progestational steroids. AB - The dynamics of the secretion of human chorionic gonadotropin (hCG) were studied by culturing explants of normal term placentas for as long as 144 hours. A significant accumulation of immunoreactive hCG (beta-subunit) was first detected at 48 to 72 hours, and a sixfold increase in hCG was observed in control culture medium at 144 hours. Compared to control cultures, progesterone (P < 0.001) in physiologic tissue levels of 5 to 20 micrograms/ml, pregnenolone (P < 0.001), 20 micrograms/ml, and 20 alpha-dihydroprogesterone (P < 0.001), 20 micrograms/ml, suppressed the secretion of hCG throughout the study period. Progesterone decreased the secretion of hCG in a dose-response manner (r = -0.8S87, P < 0.1). No suppression of hCG was observed in the presence of cortisol, testosterone, dihydrotestosterone, 17 beta-estradiol, or estriol. The secretion of human chorionic somatomammotropin was unchanged in the presence of progesterone. The augmented hCG response in the presence of dibutyl cAMP (P < 0.001) was significantly, but not completely, suppressed by progesterone 20 micrograms/ml culture medium (P < 0.01). Under these conditions progestational steroids or their immediate metabolites suppress the secretion of hCG, and they may be responsible for the decline in the levels of hCG during pregnancy. PMID- 6254362 TI - Adult manifestation of congenital adrenal hyperplasia due to incomplete 21 hydroxylase deficiency mimicking polycystic ovarian disease. AB - This study was carried out to document the postpubertal presentation of congenital adrenal hyperplasia (CAH), to elaborate the diagnostic criteria for it, and to investigate family members of CAH patients. Serum 17 hydroxyprogesterone (17OHP) was measured in normal women and 25 hirsute oligomenorrheic patients, five of whom were shown to have CAH. These five CAH patients, as a group, had significantly elevated levels of 17OHP when compared to normal and hirsute women, although the other 20 hirsute oligomenorrheic women also had higher levels of 17OHP than the follicular phase control subjects. A single intravenous bolus of 0.25 mg of adrenocorticotropic hormone (ACTH) caused much larger increased in 17OHP in all five CAH patients than in the control and hirsute women. The five CAH patients had decreased cortisol but normal 11 deoxycortisol responses to ACTH, thus indicating 21-hydroxylase deficiency (21HD). Clinically, they were indistinguishable from women with polycystic ovarian disease (PCO) and had basal serum levels of androgens and urinary 17 ketosteroids which were similar to those found in 47 other women presenting with the complaint of hirsutism. However, the androstenedione levels and androstenedione/cortisol ratios in response to ACTH were significantly higher in the five CAH patients than in both the normal and hirsute women. Of seven family members tested, two fathers and one mother had an intermediate 17OHP response to ACTH, thus suggesting heterozygosity. Human lymphocyte antigen (HLA) typing on family members indicated that the inheritance of the disorder may be linked to B antigens. Two siblings of one of the CAH patients had normal 17OHP responses to ACTH and also had a different HLA-B complement. These data document the existence of adult manifestation of CAH, due to 21 HD. This disorder presents with androgen excess and oligomenorrhea or amenorrhea and mimicks PCO. The diagnosis of it hinges upon the post-ACTH rise in 17OHP, whereas the levels of serum androgens and urinary 17-ketosteroids may be inconclusive. PMID- 6254363 TI - The induction of immunoblastic T cell sarcomas by virus-transformed prothymocytes. AB - The ontogeny of thymus-dependent lymphoid tumors induced by murine sarcoma-murine leukemia virus (MSV-MuLV) was investigated. Tumors that developed in spleens of infected mice 6 or more months after the injection of virus were diagnosed as immunoblastic T cell sarcomas. Cells derived from the tumors and established as a continuous cell line expressed the thymus leukemia (TL), brain-associated theta (BAT), and Qa2 cell surface antigens but lacked either the Ly 1 or Ly 2, 3 mature T cell differentiation antigens. In addition, the tumor cell expressed c type viral antigens, and had receptors for the lectin peanut agglutinin. The tumor cells were inert when tested for their capacity to respond in several functional T cell assays. Taken together, these data support the hypothesis that the primary target of malignant transformation by MSV-MuLV is a prothymocyte. PMID- 6254365 TI - Effects of deuterium oxide on mechanics and energetics of skeletal muscle contraction. AB - Mechanics and energetics of contraction were studied in isolated frog semitendinosus muscles (n = 15) in deuterium oxide (D2O) at 5 degrees C. Twitch force and energy liberation (heat + work) in 99.8% D2O-Ringer at lo were 4 +/- 0.8 and 22 +/- 1%, respectively, of control values. Tetanus force was slowed in development, and developed tetanus force was reduced to 89 +/- 7% of control values. With repeated tetanic contractions, the rate of force development increased, and peak force increased above control values in some muscles. The twitch was potentiated 10-fold (10 +/- 2) after repeated tetanic contractions. Energy liberation increased but not in proportion to force. Ca2+ cycling energy liberation or activation heat, estimated from stretched muscles, was 60 +/- 3% of control values. With maximum posttetanic twitch potentiation, the activation heat increased by 25 +/- 3%. Peak twitch force and energy liberation occurred at longer muscle lengths than in normal Ringer. After correcting for small differences in force development at lo and 1.38 +/- 0.01 lo, it was possible to estimate the effect of length per se on energy liberation. Under these conditions, there was an 8 +/- 2% decrease in energy liberation at 1.38 lo. PMID- 6254366 TI - Enzyme levels in individual rat muscle fibers. AB - Individual muscle fibers from the rat anterior tibialis and soleus muscles were each analyzed in duplicate for lactate dehydrogenase (LDH, EC 1.1.1.27), malate dehydrogenase (MDH, EC 1.1.1.37), 3-hydroxyacyl-CoA dehydrogenase (EC 1.1.1.35), fumarate hydrotase (EC 4.2.1.2), glycogen phosphorylase (EC 2.4.1.1), 6 phosphofructokinase (EC 2.7.1.11), pyruvate kinase (EC 2.7.1.40), fructose bisphosphatase (EC 3.1.3.11), and creatine kinase (EC 2.7.3.2). A few fibers were also analyzed for adenylate kinase (EC 2.7.4.3). In general, there was a wide and almost continuous spectrum of coordinated enzyme activities. In the tibialis muscle, two fiber groups could be clearly distinguished on the basis of MDH activity. The high MDH group had on the average lower LDH activity, but there was a great deal of overlap in LDH between the two groups. Less overlap was observed for phosphorylase and fructose-bisphosphatase, both inversely related to MDH. Only one main group of fibers (presumably slow twitch) was found in the soleus muscle, although enzyme activities also covered a wide range. These soleus fibers were clearly distinguished from the high MDH tibialis group by much lower activities of LDH, pyruvate kinase, and fructose-bisphosphatase. PMID- 6254367 TI - Characteristics of calcium transport and binding by rat myometrium plasma membrane subfractions. AB - A gradient has been designed to yield two subfractions of plasma membrane vesicles from rat myometrium, a low buoyant density (8-24% sucrose) fraction N1 richer in 5'-nucleotidase and a higher buoyant density (24-30% sucrose) fraction N2, instead of a previously described fraction F1. Both N1 and N2 had very low activities of NADPH-cytochrome c reductase and succinate-cytochrome c reductase. Electron micrographs of thin sections of N1 showed clear vesicles, whereas N2 consisted of vesicles with electron-dense bodies attached to them. These plasma membrane vesicles can actively take up Ca. The active uptake of Ca was potentiated by oxalate and phosphate and abolished by the Ca ionophore A23187. Dilution of actively loaded vesicles in isotonic media containing EGTA led to loss of a small proportion of the stored Ca instantaneously and the remainder more slowly in a biphasic manner. Dilution in hypotonic media with EGTA led to a release of a much larger proportion of the accumulated Ca. A23187 at high concentrations (10 microM) caused a release of all the sequestered Ca whether the active Ca uptake had been carried out in the presence or in the absence of oxalate. A23187, 0.5 microM, released all the sequestered Ca from the vesicles that were actively loaded in the absence of oxalate, but only 37% when the vesicles were actively loaded with Ca in the presence of oxalate. Comparison of the composite plasma membrane fraction F1 (8-30% sucrose) and the subfractions N1 and N2 showed that they had different capacities for Ca uptake in the presence and absence of ATP. An attempt has been made to analyze the active Ca-uptake data in terms of various Ca pools. PMID- 6254368 TI - Effect of verapamil on the hydroosmotic response to antidiuretic hormone in toad urinary bladder. AB - To investigate the role of the calcium ion in the hydroosmotic response to antidiuretic hormone (ADH), the effects of verapamil, an inhibitor of calcium ion entry into cells, on stimulated water flow was examined in vitro in the toad urinary bladder. Verapamil, 50 micro M, decreased ADH-stimulated osmotic water flow from 23.4 +/- 4.1 to 9.9 +/- 3.3 mg . min-1 . hemibladder-1 (mean +/- SE, n = 12, P < 0.001). That this inhibitory effect was due to a verapamil-induced alteration in cellular calcium metabolism is suggested by the findings that 45Ca2+ uptake by isolated toad bladder epithelial cells was reduced nearly 50% in the presence of verapamil and that reversibility of verapamil's inhibitory action was calcium dependent. Additionally, verapamil reduced theophylline- (20 mM) stimulated water flow from 22.8 +/- 2.7 to 9.5 +/- 2.9 mg . min-1 . hemibladder-1 (n = 7, P < 0.001) but enhanced cAMP- (10 mM) induced water flow from 12.8 +/- 2.5 to 21.6 +/- 1.1 ng . min-1 . hemibladder-1 (n = 7, P < 0.001). The latter effect was due, at least in part, to a direct inhibitory effect by verapamil on phosphodiesterase activity of toad bladder homogenates. These results, therefore, suggest that the calcium ion is an important coupling factor at the level of the adenylate cyclase enzyme complex for the stimulus-reabsorption coupling between ADH and the transporting epithelia of the toad urinary bladder. PMID- 6254369 TI - Blood pressure and renal function during chronic changes in sodium intake: role of angiotensin. AB - The present study was designed to quantitate the role of the renin-angiotensin system (RAS) in determining the chronic relationships between arterial pressure (AP), renal hemodynamics, and Na excretion. In six control dogs, Na balance was achieved during chronic step increases in Na intake from 5 to 500 meq/day with small increases in AP (<7 mmHg), moderate increases in GFR (19%), and decreases in filtration fraction (FF) and plasma renin activity. Similar increases in Na intake in six dogs with angiotensin II (AII) fixed, due to constant intravenous infusion of 5 ng . kg-1 . min-1 AII, caused large increases in AP (42%), GFR (31%) FF, and calculated renal Na reabsorption (TNa) above control. In six dogs with AII formation blocked with SQ 14,225, Na balance at intakes of 5-80 meq/day occurred at reduced AP, GFR, FF, and TNa, although plasma aldosterone concentration (PAC) was not substantially different from that in control dogs. At Na intakes above 240 meq/day, AP was not altered by SQ 14,225. These data indicate that during chronic changes in Na intake the RAS plays a major role, independent of changes in PAC, in allowing Na balance without large changes in GFR or AP. The mechanism whereby AII conserves Na chronically is through increased TNa, since steady-state TNa was increased by AII and decreased by SQ 14,225. PMID- 6254370 TI - Mechanism of activation of renal Na+-K+-ATPase in the rat: effects of reduction of renal mass. AB - The mechanism of activation of renal Na+-K+-ATPase was studied in rats 2 wk after unilateral nephrectomy. The increase in enzyme specific activity was confined to the outer medulla and occurred without changes in the cellular contents of RNA or protein. Enzyme activation was accompanied by increases in the levels of the phosphorylated intermediate with little or no change in the apparent turnover numbers of the reaction. The specific activity of the ouabain-sensitive p nitrophenylphosphatase also increased by uninephrectomy but to a larger extent than did Na+-K+-ATPase. Kinetic studies demonstrated an increase in Vmax for ATP, sodium, and potassium, and small increases in Km for ATP and K1/2 for potassium. There was no change in the activation energies or phase transition temperature to indicate alterations in the membrane environment of Na+-K+-ATPase. Adrenalectomy did not adversely affect activation. These results indicate that activation of renal Na+-K+-ATPase after reduction of renal mass occurs mainly by an increase in the number of sodium pump sites. PMID- 6254364 TI - Viral myocarditis. A review. PMID- 6254371 TI - Covalent modification and inhibition of an epithelial sodium channel by tyrosine reactive reagents. AB - This study sought to elucidate the molecular mechanism involved in the Na+ entry across the apical membrane of the urinary bladder of the toad. Na+ transport, as measured by short-circuit current (SCC), was irreversibly inhibited by three tyrosine-specific reagents: N-acetylimidazole (ID50, 4.6 x 10(-2)M), tetranitromethane (1.8 x 10(-4) M), and 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl; 3.4 x 10(-5) M). The functional specificity of NBD-Cl to block Na+ entry via Na+ channels was attested by the following: 1) NBD-Cl produced comparable inhibition of SCC and Na+ influx under aerobic and anaerobic conditions; 2) amphotericin B produced complete recovery of inhibited SCC; 3) vasopressin increased SCC only in proportion to the uninhibited SCC; 4) Km for Na+ was not changed; and 5) the half time for the inhibition varied as a function of amiloride concentration or pharmacologic activity of its analogues. On the basis of the above findings, these tyrosine-specific reagents are believed to be useful chemical probes for the identification and characterization of Na+ channel protein. PMID- 6254372 TI - Left stellate stimulation: regional myocardial flows and ischemic injury in dogs. AB - The effects of left stellate ganglion stimulation (LSGS) on regional myocardial blood flow (RMBF) and epicardial S-T segment were investigated in the normal and ischemic myocardium of anesthetized dogs. In nonischemic myocardium LSGS decreased calculated coronary resistance, increased RMBF, and reduced the endocardial-to-epicardial (endo-to-epi) ratio. These effects were reversed after atenolol (1 mg/kg) and abolished after combined atenolol and phenoxybenzamine (3 mg/kg) treatments. In ischemic myocardium LSGS did not change RMBF but increased S-T segment. However, after atenolol, LSGS increased ischemic RMBF and the ischemic-to-nonischemic areas flow ratio (reverse coronary steal phenomenon), these effects being abolished by phenoxybenzamine. We conclude that 1) LSGS increases RMBF and decreases endo-to-epi ratio in nonischemic areas by beta 1 adrenergic stimulation through metabolic autoregulation, 2)beta 1-adrenergic blockade in nonischemic areas unmasks alpha-adrenergic vasoconstriction inducing a redistribution of flow towards ischemic areas, and 3) further elevation of S-T segment by LSGS is due to oxygen requirements enhancement by beta 1-adrenoceptors stimulation. PMID- 6254373 TI - Inhibition by adenosine of catecholamine-induced increase in rat atrial contractility. AB - Because adenosine has been shown to attenuate the catecholamine-induced increase in myocardial cAMP formation and glycogen phosphorylase activity (Circ. Res. 43: 785-792, 1978), the present study was undertaken to determine whether the nucleoside inhibits the catecholamine-elicited increase in cardiac contractile state. Isolated rat atria were bathed in oxygenated physiologic saline and stimulated to contract isometrically at 2/s. Isoproterenol (0.1 microM) increased peak contractile force (PCF) by 96% and the rate of force development (+dF/dt) by 107%. Adenosine (10 microM) alone had no effect on these contractile parameters. Isoproterenol in the presence of adenosine increased PCF and +dF/dt only 15 and 14%, respectively. Elevation of bathing medium Ca2+ or administration of dibutyryl cAMP (DBcAMP) increased PCF and +dF/dt, but these responses were not decreased by adenosine. Inosine, adenine, adenosine 5'-monophosphate, and guanosine inhibited the isoproterenol-induced responses 5-22%. The results indicate that adenosine markedly inhibits, whereas some related purines only mildly attenuate, the catecholamine-elicited, but not the Ca2+- or DBcAMP elicited, increases in contractility. Thus, adenosine may antagonize catecholamine-elicited glycogenolysis and enhanced contractile state in the heart by exerting an effect at the level of, or proximal to, cAMP formation. PMID- 6254374 TI - Widespread distribution and rate differentiation of the atrial pacemaker complex. AB - In a study to examine the basis of rate-related changes in the electrocardiographic P wave we found a multicentric rather than unifocal origin of the atrial depolarization wave in dogs. Three to five pacemakers, or origin points, were distributed over a 30- to 40-mm area compared to the 11-mm size of the sinus node. Two or three of the sites could excite simultaneously, or one specific site would dominate excitation. Each separate origin point dominated excitation within a specific range of heart rates, and on reaching either the upper or lower limits of this range, a new focus abruptly dominated and initiated the atrial wave front. We have obtained evidence to suggest that these findings may be explained by a widely distributed atrial pacemaker complex. The spatial distribution of this system exceeded the dimensions of the canine sinus node by a factor of three to four times. The pacemaker centers, although distributed, were consistently located at specific positions along the superior vena caval-right atrial junction. Also, each separate pacemaker site appeared functionally differentiated to generate a specific range of heart rates. We propose that in addition to the sinus node there are other specialized atrial pacemaker centers, and that this specialization, including the differentiated response and coordination, is conferred by focal receptor characteristics and their inputs. PMID- 6254375 TI - Evaluation of presynaptic alpha-receptor function in the canine renal vascular bed. AB - The functional significance of presynaptic alpha-receptor modulation of sympathetic nerves was examined in vivo in the canine renal vascular bed. In pentobarbital-anesthetized dogs, the vasoconstrictor response to renal nerve stimulation and exogenous norepinephrine was compared before and during intra arterial infusions of epinephrine, oxymetazoline, clonidine, and norepinephrine. Only epinephrine produced a modest decrease in stimulation-induced vasoconstriction at 1 Hz. After pretreatment with desipramine, intra-arterial infusions of epinephrine or norepinephrine did not alter stimulation-induced vasoconstrictor responses relative to exogenous norepinephrine. Further, neither yohimbine nor phentolamine (10(-9) to 10(-3) g, intra-arterial) produced a distinctly increased vasoconstrictor response to nerve stimulation relative to exogenous norepinephrine. Thus, studies using alpha-receptor agonists, antagonists, and inhibition of neuronal uptake failed to reveal a physiologically significant alpha-receptor-mediated negative feedback mechanism for stimulation induced vasoconstriction in the canine renal vascular bed. PMID- 6254376 TI - Sympathetic nerve function and vascular reactivity in Doca-salt hypertensive rats. AB - The present study was conducted to measure norepinephrine release during sympathetic nerve stimulation and to evaluate vascular reactivity in the isolated perfused mesenteric vasculature of normotensive and Doca-salt hypertensive rats. Significantly greater vasoconstrictor responses to periarterial nerve stimulation, norepinephrine, and vasopressin, but not to barium chloride, were observed in the mesenteric vasculature of the hypertensive rats in comparison with the control normotensive group. Norepinephrine release, measured as total tritium overflow, during periarterial nerve stimulation at 4 Hz for 2 min, was identical in both normotensive and hypertensive animals. Phentolamine (5.3 micro M) significantly increased tritium overflow, but to the same extent in the normotensive and the hypertensive mesenteric vasculature, suggesting that the negative feedback presynaptic alpha-adrenoceptor mechanism, which has been proposed to modulate transmitter release, was unaltered in this form of hypertension. These results indicate that hyperresponsiveness of the mesenteric vasculature to periarterial nerve stimulation in the hypertensive rats is due to increased sensitivity of the vascular alpha-adrenoceptor and not facilitation of the transmitter release. The increased vascular reactivity to norepinephrine and vasopressin may be involved in the maintenance of Doca-salt hypertension. PMID- 6254377 TI - Diurnal changes in amplification of hormone rhythms in the adrenocortical system. PMID- 6254378 TI - Potassium ion as a regulator of adrenal angiotensin II receptors. AB - The importance of potassium as a regulator of angiotensin II receptors of two target tissues has been investigated by combining high-K+ diet in rats with a converting enzyme inhibitor (Captopril; SQ 14,225) or angiotensin II. K+ loading alone produced the characteristic increase in Ka and decrease in number of smooth muscle receptors and decrease in Ka and increase in number of adrenal receptors. The combination of Captopril and high-K+ diet blocked the development of most of these effects. In smooth muscle, the number of angiotensin II receptors was 40% higher (n = 5) and Ka was 94% lower (n = 5); in the adrenal the Ka was 29% higher (n = 4) than with K+ loading alone. However, development of the increment in number of adrenal receptors occurred in spite of Captopril treatment. In addition, angiotensin II infusion concomitantly with high-K+ diet resulted in a further increment in the number of adrenal receptors. These studies represent the first example of an ion as a regulator of a peptide hormone receptor and emphasize that different mechanisms of regulation are involved in adrenal and smooth muscle. PMID- 6254380 TI - Mucosal gastrin receptor. IV. Binding specificity. AB - We used membrane preparations of rat oxyntic gland mucosa to test the binding of various gastrin analogues to the gastrin receptor. Using [125I]15-Leu G-17 as a marker, a concentration of 4 X 10(-9) M unlabeled G-17 inhibited binding 50%. The tetra-, penta-, and hexapeptides of gastrin caused similar 50% inhibitions of binding at concentrations of 1 X 10(-7) M, 3 X 10(-8) M, and 7 X 10(-9) M, respectively. The heptapeptide caused only slightly less inhibition than G-17, whereas the decapeptide was equivalent in potency. Neither the G-17 nor G-34 that had the active tetrapeptide removed caused 50% inhibition of binding. When compared to G-17, these analogues produced only a 25% inhibition of binding at concentrations of 10(-8) M. We also failed to inhibit binding more than 25% when we used an analogue that had the amide removed from the C-terminal phenylalanine. Atropine, metiamide, and mepyramine did not alter the binding of gastrin to receptor. The results of binding specificity approximate the changes in biological potency associated with these compounds. This study adds further support that the gastrin receptor in question is responsible for the physiological effects of the hormone. PMID- 6254379 TI - Effects of PTH, ADH, and cyclic AMP on distal tubular Ca and Na reabsorption. AB - Tubular microperfusion experiments were performed in rats to examine the effects of thyroparathyroidectomy (TPTX), parathyroid hormone (PTH), antidiuretic hormone (ADH), and cyclic AMP (cAMP) on distal tubular Ca, Na, and water reabsorption. TPTX caused a significant decrease in the Ca reabsorptive rate as compared to intact animals. PTH (5 U/kg; 2 U x kg-1 x h-1) replacement in TPTX animals restored Ca transport to control levels. Application of either cAMP (10(-3) M) or 8-(p-chlorophenylthio)-cyclic 3',5'-adenosine monophosphate (10(-5) M) to the surface of the kidney caused a stimulation of Ca reabsorption similar to that produced by PTH. Neither TPTX nor PTH changed Na or water reabsorption significantly, whereas the cyclic nucleotides increased both of these parameters. These later actions of cAMP duplicated effects of ADH observed in these distal tubules. PMID- 6254381 TI - Immunohistochemical evaluation of a complex endocrinopathy. AB - A patient with clinical and biochemical evidence of ectopic ACTH production is described. Autopsy revealed endocrine tumors of bronchus and pancreas with metastases to the liver, kidney, abdominal lymph nodes, and bone. Immunohistochemical methods established that the bronchial and pancreatic tumors were separate primary neoplasms each with its own hormone production; and allowed us to determine that the bronchial carcinoid was the source of ACTH and gave rise to the liver metastases, and that insulin was present in the cells of the pancreatic islet cell tumor. These methods also revealed a mild C-cell hyperplasia of the thyroid gland. We wish to stress the importance of the immunoperoxidase method in the evaluation of this and similar polyendocrine cases. PMID- 6254382 TI - Protection against amebic liver abscess in hamsters by means of immunization with amebic antigen and some of its fractions. AB - Immunization of hamsters by intramuscular injections of an amebic extract and of two of its fractions, emulsified with complete Freund's adjuvant, resulted in protection against the development of amebic liver abscess, following intrahepatic inoculation of axenic trophozoites of Entamoeba histolytica such that Fraction I, Fraction II, and the whole antigen conferred protection to 18 out of 18, 4 out of 18, and 11 out of 18 hamsters, respectively. Splenomegaly was found to accompany the development of hepatic liver abscesses in this experimental system. There was a very high degree of correlation (r = 0.95) between the weights of the abscesses and the spleens. On the other hand, there was no correlation between the anti-amebic antibody titers (determined by the indirect hemagglutination test) and the development of the liver abscesses within the time-span of the experimental protocol used in this study. PMID- 6254383 TI - Surface coagglutination with formalinized, stained protein A staphylococci in the immunologic study of three pathogenic amebae. AB - The indirect immunofluorescence and, to a lesser extent, the immunoperoxidase methods have become the principal means of conducting immunological studies upon amebae. These procedures require the conjugation of fluorescein or enzyme with antiglobulin reagents and fixation of the amebae. The present report describes a somewhat similar methodology wherein formalinized, stained protein A staphylococci combined with specific antibody have been found to coagglutinate upon a portion of the amebic surface of living trophozoites in a fashion similar to direct immunofluorescence. The prepared staphylococci without attached antibody have also been found to coagglutinate in an identical fashion after the specific antibody has been deposited upon the amebic surface. This is comparable to indirect immunofluorescence reaction. A comparison of this procedure with the immunofluorescence method of identification and with measurement of titer of serum antibody is presented, which indicates that the new technique compares favorably with the immunofluorescence results. PMID- 6254384 TI - Variation in virulence for mice and rhesus monkeys among St. Louis encephalitis virus strains of different origin. AB - The virulence characteristics of 67 strains of St. Louis encephalitis (SLE) virus isolated from various sources in North, Middle, and South America were compared in mice and rhesus monkeys. Each virus strain was titrated in mice exactly 21 days old and virulence was expressed as the ratio of intracerebral (ic)/intraperitoneal (ip) LD50. Virus strains fell into three groups: 1) high virulence (ic/ip LD50 ratio approximately 1.0); 2) intermediate virulence (variable mortality over a wide dose range); and 3) low virulence (ic/ip LD50 less than or equal to 0.00002). Virus strains isolated during Culex pipiens and Cx. nigripalpus--borne epidemics in the eastern United States were highly virulent for mice, whereas a high proportion of the endemic virus strains isolated from Cx. tarsalis in the western United States were attenuated. Virus strains isolated from birds (the usual host for SLE virus) were highly virulent, in contrast to strains from rodents and carnivores, which were attenuated. Isolates from humans exhibited variable virulence characteristics. In experimentally-infected mice, virulence correlated with high viremia, replication in extraneural tissues, and earlier neuroinvasion. Mouse virulence correlated with clinical and histopathologic markers of pathogenicity for ic inoculated rhesus monkeys. Monkeys immunized with nonpathogenic strains by subcutaneous inoculation were partially protected against ic challenge with a virulent virus strain. The virulence classification of SLE virus strains is discussed in terms of epidemiologic correlations. This classification provides a framework for future studies on the antigenic, genetic, and biochemical bases for SLE virus strain variation. PMID- 6254385 TI - Equine Getah virus infection: isolation of the virus from racehorses during an enzootic in Japan. AB - A primary enzootic of equine Getah virus infection involving 722 of 1,903 racehorses occurred at a training center in Japan between September and November of 1978. Sixty-two viral agents were isolated from the plasma of 209 sick horses which exhibited pyrexia with rectal temperatures ranging from 38.5--40 degrees C, urticarial rash on various portions of the body, and edema of the hind legs. The viruses were antigenically related to the AMM 2021, Haruna, and Sagiyama strains of Getah virus. Infection and disease were produced experimentally in horses when inoculated by the intramuscular or intranasal routes. PMID- 6254387 TI - [Case of a mixed mesodermal tumor]. PMID- 6254386 TI - Characterization of pathogenic trypanosomatidae by restriction endonuclease fingerprinting of kinetoplast DNA minicircles. AB - A simple protocol was developed for the routine preparation of a kinetoplast DNA fraction from trypanosomatids. The digestion of this DNA with selected restriction endonucleases, followed by the electrophoretic analysis of the fragments on polyacrylamide gradient gels, yielded characteristic patterns that could be used for the intrinsic characterization of stocks (populations derived by serial passage in vivo and/or in vitro from a primary isolation, without any implication of homogeneity or characterization), strains (sets of populations originating from a group of trypanosomes of a given species or subspecies present at a given time in a given host or culture, and defined by the possession of one or more designated characters), and clones (trypanosomes derived from a single individual by binary fission) of certain pathogenic hemoflagellates. PMID- 6254388 TI - Persistent renal blastema (nephroblastomatosis) as a frequent precursor of Wilms' tumor; a pathological and clinical review. Part 2. Significance of nephroblastomatosis in the genesis of Wilms' tumor. AB - The historical development of the concept of nephroblastomatosis is reviewed. Subtypes of nephroblastomatosis are described, and their interrelationships are discussed. PMID- 6254389 TI - [Simultaneous determination of plasma cAMP and cGMP in asthmatic patients]. PMID- 6254390 TI - Assay for radiolabeled type IV collagen in the presence of other proteins using a specific collagenase. PMID- 6254391 TI - Ligand: a versatile computerized approach for characterization of ligand-binding systems. PMID- 6254392 TI - Separation of 5'-ribonucleoside monophosphates by ion-pair reverse-phase high performance liquid chromatography. PMID- 6254393 TI - Calcium protects DNase I from proteinase K: a new method for the removal of contaminating RNase from DNase I. PMID- 6254394 TI - Simultaneous analyses of clostridium collagenase and neutral proteinase activities with a single synthetic substrate. PMID- 6254395 TI - Fluorescence spot tests for DNA endonuclease, ligase, and topoisomerase activities. PMID- 6254396 TI - Responses of mouse spleen morphology to the growth of subcutaneously injected virally transformed cells. AB - The changes in the fractional volume of six structural components in the spleens of Balb/C mice injected with Herpes simplex virus Type 2-transformed cells (H238 tumor cells) were quantitated during progressive tumor growth. Spleen stereology was performed at three time intervals during the early stages of tumor development. The results revealed that the volume of the compact myeloid tissue and reaction center of lymphoid nodules increased about four- to five-fold from 10 to 33 days after H238 tumor cell injection. A progressive increase was also seen in the red pulp volume. Although an increase in volume of the marginal zones around the lymphoid nodules was evident early during the test period, by day 33 the mean value was similar to the control value. These results indicate that the spleen undergoes significant morphological changes in three splenic components during progressive growth of a tumor produced by subcutaneous injection of a virally-transformed cell line. PMID- 6254397 TI - [Dynamics of tubarine action in relation to infusion and transfusion therapy under combined anesthesia]. PMID- 6254398 TI - [Mechanisms of brain mitochondrial injury in cerebral ischemia]. PMID- 6254399 TI - Establishment of a canine cell line: derivation, characterization, and viral spectrum. AB - A cell line, designated A-72, for virus studies was established from a tumor surgically removed from a female, 8-year-old Golden Retriever dog. Following explant culture, the cells were serially passaged 135 times. The A-72 cells maintained a fibroblastic appearance and, at the 123rd passage, had a population doubling time of approximately 27 hours. Karyotypic analysis of the high passage cells showed the modal 2n chromosome number was 92 to 93. Using starch gel electrophoresis for enzyme characterization, the electrophoretic mobilities of enzymes extracted from A-72 cells were identical with those of canine peritoneal fibroblasts and primary canine kidney cells. The A-72 cells were susceptible to infection with infectious canine hepatitis virus, canine adenovirus type II, canine herpesvirus, canine parainfluenza virus, and canine coronavirus, but were not susceptible to canine distemper virus or the minute virus of canines. These cells have been particularly useful for studies of the fastidious canine coronaviruses, as the commonly used primary canine kidney cells exhibit varied susceptibility to these viruses. PMID- 6254400 TI - Immunologic phenomena in the effusive form of feline infectious peritonitis. AB - The effusive form of feline infectious peritonitis (FIP) was reproduced by injecting 12- to 16-week-old kittens intraperitoneally with a cell-free inoculum derived from the tissues of infected cats. The kittens used for the study were either positive for FIP virus-reacting antibodies before inoculation or they were seronegative. Seropositive kittens were obtained from a cattery where the natural infection was enzootic, and seronegative kittens were obtained from a specific pathogen-free cattery. Only about half the kittens that were seronegative before inoculation developed disease or serum antibodies to the tissue-derived virus. Seronegative kittens that developed disease showed no signs of illness until 8 to 10 days after inoculation, and they lived for 7 to 14 days after clinical signs appeared. The onset of clinical disease coincided with the appearance of serum antibodies. In contrast, all of the seropositive kittens became ill within 36 to 48 hours after inoculation, and died within 5 to 7 days. If seronegative kittens were treated with immune serum or immunoglobulin (Ig)G, they developed disease with the same frequency, acuteness, and severity as seropositive kittens. Foci of hepatitis and serositis in seropositive kittens contained viral antigen, IgG bound to antigen, and complement. Serum complement activity also decreased several days before death in seropositive kittens inoculated with tissue-derived FIP virus. The temporal relationship of clinical disease and the appearance of serum antibodies, the more acute and severe nature of the disease produced in seropositive kittens, and the presence of antibody and complement in the lesions indicated that effusive FIP is immunologically mediated. PMID- 6254402 TI - Cell-mediated immunity against turkey coronaviral enteritis (bluecomb). AB - Studies on cell-mediated immune response in turkeys infected with turkey coronavirus (TCV) were made. A whole blood culture technique was developed for quantitatively evaluating in vitro lymphocyte reactivity to mitogens concanavalin A, phytohemagglutinin-P, and TCV antigen. The degree of blastogenesis was quantitated by the measurement of the uptake of the [125I]deoxyuridine in the presence of fluorodeoxyuridine. The stimulation indices were consistently higher in the infected birds compared with those in the noninfected controls, and they were statistically significant (P < 0.05). The detection of TCV specific responses indicated that cell-mediated immunity may be important in determining the immunity against turkey coronaviral enteritis. The whole blood lymphocyte transformation assay was emphasized as a convenient and useful in vitro indicator of cell-mediated immunity in TCV infection. PMID- 6254401 TI - Effects of level of nitrogen fertilization of fescue pasture on gastrointestinal parasitism of beef cattle. AB - Two established tall fescue pastures were used in a 4-year study of the relationship between the level of gastrointestinal parasitism in cattle and the level of nitrogen fertilization of the pasture. One pasture was fertilized with 224 kg of NH4NO3/ha each year and served as the control. A second pasture, referred to as the low-fertilized (LF) pasture, was fertilized with N at 84 kg/ha the first year and 74 kg/ha in each of the next 3 years. Both pastures were stocked with Angus cows (2.5/ha) and their calves. Rectal fecal samples obtained every 6 weeks from 10 cows and as many calves as possible in each pasture were examined for nemotode eggs and coccidia oocysts. Two calves from each group were slaughtered at the end of each of the last 3 years to determine the numbers and species of parasites. Cows had significantly lower egg counts than did the calves. Egg counts did not differ between the two groups of cows, but the control cows had higher average weights than the cows on the LF pasture. Control calves had significantly lower egg counts than the calves on the LF pasture, but only slightly higher mean adjusted 205-day weights. At necropsy, significantly fewer worms were recovered from the controls (17,977) than from the LF-pastured calves (52,332). Cooperia oncophora was the predominant species. The level of coccidia infection did not differ between the two groups of cows and calves. The greater availability of forage in the control than in the LF pasture probably was responsible for the lower level of parasitism in the control calves and for the greater weight gains made by the control cows and calves. PMID- 6254403 TI - Rotavirus antibody in chickens as measured by enzyme-linked immunosorbent blocking assay. AB - The antibody titer of 202 chickens to SA-11 rotavirus was determined by enzyme linked immunosorbent blocking assay. The chickens were from 15 separate flocks on six farms. The titer was detectable (1:18 or greater dilution) in 43% of the chickens. The wide variation in infection rate between flocks on individual farms (0% to 90%) indicated there is probably not significant transmission of the virus between flocks on the farm. Significant differences in numbers of serotest positive birds were found between separate farms, possibly reflecting different management practices. PMID- 6254404 TI - Identification and characterization of a bovine rhinovirus isolated from Iowa cattle with acute respiratory tract disease. AB - Viral isolate FS1-43 isolated from a calf with acute respiratory tract disease was characterized as a bovine rhinovirus. This virus was antigenically indistinguishable from rhinovirus strains C-07 and VC-96. The virus replicated in low passage Madin-Darby and Georgia bovine kidney cells. A relative noncytopathogenic replication occurred in epithelial bovine turbinate, bovine fibroblastic turbinate, and bovine lung cells. Ciliary activity of tracheal explants was unaffected during eight serial passages. Viral replication was detected earlier and viral titers were higher at 33 C than at 37 C. Rotation of cultures did not affect viral titers but was necessary to produce a cytopathic effect in Madin-Darby bovine kidney cells. PMID- 6254405 TI - Altered metabolism, acute shock, and therapeutic response in a calf with severe coronavirus-induced diarrhea. AB - Acute shock and metabolic failure appeared in a diarrheic calf being studied intensively to determine kinetics of glucose and lactate metabolism. Intravenous therapy significantly improved its condition. During metabolic failure, the rapid increase in blood lactate and concomitant decrease in glucose were due to inhibited gluconeogenesis, as glucose entry and lactate oxidation were not modified. Therapy restored metabolic activity and decreased the severe hyperkalemia. PMID- 6254406 TI - Abnormalities and virus-like particles in spermatozoa from bulls latently infected with bluetongue virus. AB - Abnormalities were commonly observed in spermatozoa, and bluetongue virus (BTV) was isolated from semen of 2 known BTV carrier bulls and 2 of 4 BTV seropositive field bulls. The spermatozoal abnormalities ranged from a small cavity between the acrosome and nucleus with some involvement of the nucleus, to an enlargement of the cavity accompanied by vesiculation that could affect the entire acrosome. Virus-like particles were occasionally observed in the affected spermatozoa, but were present in all samples. A positive relationship was found between infectivity of semen samples from BTV latently infected bulls and the observation of abnormalities and virus-like particles in the heads of affected spermatozoa. PMID- 6254407 TI - Chemotherapeutic value of 2-deoxy-D-glucose in infectious bovine rhinotracheitis viral infection in calves. AB - Daily injection of 2-deoxy-D-glucose (2-dG) had no protective effect against respiratory tract infection in calves caused by infectious bovine rhinotracheitis virus. It also did not reduce the severity of this infection. Ocular instillation of the drug, however, markedly reduced the severity of viral-induced conjunctivitis and keratoconjunctivitis. The drug was effective when given at the time of ocular infection or after clinical conjunctivitis developed. PMID- 6254408 TI - Plasma glucocorticoid and circulating blood leukocyte responses in cattle after sequential intramuscular injections of ACTH. AB - Nine Holstein-Friesian cows in the same stage of lactation were randomly given IM injections of saline solution, 100 IU of ACTH, or 200 IU of ACTH for a period of 3 days at 0800 and 1600 hours on one day and at 0100 hours the next day. A dose of 100 IU of ACTH represented the amount of ACTH released during physiologic stress and 200 IU of ACTH represented a therapeutic dose. Blood samples were obtained from indwelling jugular catheters for total circulating leukocyte and total plasma corticosteroid determinations at -1, 0, 0.25, 0.50, 1, 1.50, 2, 4, 6, and 8 hours after the 0800-hour ACTH injections. Concentrations of blood leukocytes and total plasma corticosteroids were affected significantly (P < 0.05) by treatment, cow within treatment, day of injection, treatment by day interaction, time, treatment by time interaction, and day by time interaction. Total plasma corticosteroids were 5.6 ng/ml (saline), 38.9 ng/ml (100 IU of ACTH), and 59.8 ng/ml (200 IU of ACTH). Mean corticosteroid concentrations from 0.5 to 8 hours were 29.2 ng/ml on day 1, 42.5 ng/ml on day 2, and 32.7 ng/ml on day 3. Blood leukocytes were 8,545 cells/mm3 (saline, 11,241 cells/mm3 (100 IU of ACTH) and 9,777 cells/mm3 (200 IU of ACTH). When compared with basal circulating leukocyte concentrations (within cow), this represented increases of 20.7% for 100 IU of ACTH and 24.5% for 200 IU. Mean circulating leukocyte concentrations from 0.5 to 8 hours were 8,900 cells/mm3 on day 1, 10,500 cells/mm3 on day 2, and 10,000 cells/mm3 on day 3. These data indicate that the adrenal gland responded less on day 3 and that continuous stimulation of bovine adrenal glands by ACTH at physiologic and therapeutic concentration could lead to reduced synthesis or release of adrenal corticosteroids (or both) with concomitant reduction in the concentration of total circulating leukocytes. PMID- 6254409 TI - Susceptibility of nonhuman primate species to infection by simian rotavirus SA 11. AB - Enzyme-linked immunosorbent assay examination of sera from three nonhuman primate species demonstrated the presence of antibody reacting with simian rotavirus SA 11 and calf rotavirus C486. The occurrence of this antibody in sera from adult, wild-caught animals suggests natural rotovirus infection. The occurrence of antibody was highest in the chimpanzee and declined, respectively, in the rhesus macaque and in the squirrel monkey. Inoculation of three infant rhesus macaques, a nursery-reared chimpanzee, and a cesarian-derived nursery-reared baboon with SA 11 virus resulted in enteric infection, with virus excretion beginning 48 to 72 hours after oral administration of the virus. Clinical disease, as manifested by diarrhea, was observed only in the chimpanzee. Inoculation of ten squirrel monkeys, from 30 to 191 days old, induced infection only in the monkey inoculated at 30 days of age. This monkey became ill within 48 hours after viral administration and was euthanatized. Necropsy demonstrated a generalized infection, with virus recovered from lung, liver, kidney, spleen, and intestine. The remaining nine inoculated squirrel monkeys failed to develop enteric infection and did not respond with antibody to SA-11 virus. PMID- 6254410 TI - Possible factors influencing the immunoglobulin G concentration in swine colostrum. AB - The immunoglobulin (Ig) G concentration in swine colostrum was determined by the single radial immunodiffusion method, using 157 samples collected from farm raised sows in the Yamaguchi Prefecture of Japan during 1976 and 1977. The mean IgG value was 53.03 mg/ml, and the maximum and minimum values were 101.39 mg/ml and 11.74 mg/ml, respectively. The amount of IgG varied greatly among sows. To clarify the possible factors influencing the amount of IgG in colostrum, the following items were surveyed: season, district, breed, age of sows, number of parturitions, udder section from which samples were collected, kind of feed, vaccinations of swine erysipelas live-organism vaccine, hog cholera live-virus vaccine, Japanese encephalitis live-virus vaccine, tramsmissible gastroenteritis liver-virus vaccine, type of farming, and number of sows raised on a farm. Relationships between the amount of IgG in colostrum and each of these 13 items were analyzed. Seemingly, strong correlations with the amounts if IgG in colostrum were found with five items (district, number of parturitions, kind of feed, type of farming, and number of sows). To the contrary, five items (age, udder section, and vaccinations of swine erysipelas live-organism vaccine, hog cholera live-virus vaccine, and Japanese encephalitis live-virus vaccine) had poor correlations. Other items had moderate correlations. The multiple correlation coefficient obtained was 0.5499. PMID- 6254411 TI - Escherichia coli heat-stable enterotoxin in feces and intestines of calves with diarrhea. AB - Two experiments were conducted to evaluate detection of Escherichia coli heat stable enterotoxin (ST) in the feces of calves as a method for implicating E coli in neonatal calf diarrhea. The first experiment evaluated the use of the infant mouse test for detection of ST in the feces of calves with naturally occurring diarrhea. Simultaneous identification of bovine enteropathogenic strains of E coli (EEC) and of other infective agents implicated in neonatal calf diarrhea was attempted in these samples. The ST was detected with certainty in only 7 of 41 samples from calves less than or equal to 3 weeks old. Enteropathogenic E coli, however, was detected in 27 samples. In 23 of these 27 samples, EEC was the only recognizable diarrheagenic agent. In a small percentage of the samples, Salmonella, rotavirus, coronavirus, and cryptosporidium were recognized alone, in combination with each other, or with EEC. In the second experiment, 6 calves were fed colostrum from cows inoculated with the bovine EEC strain B44; 6 were given colostrum from cows vaccinated with non-EEC strain 28F, and 4 were given milk from nonvaccinated heifers. Two of the calves that were given colostrum from cows inoculated with strain B44 were challenge exposed with the non-EEC strain 28F. The remaining calves were challenge exposed with the EEc strain B44. Fecal samples were taken from these calves at intervals and were examined for the presence of ST and of the challenge-exposure organism. The ST was detected in approximately one half of the fecal samples obtained, and it was most often detected in the early stages of the induced diarrhea. Calves were observed to shed the challenge-exposure EEC strain for long periods in the absence of diarrhea or detectable amounts of ST in the feces. The ST was detectable in fecal samples when the diarrhea was severe and when the dry matter content of the fecal samples was low. PMID- 6254412 TI - Vaccination of pregnant ponies against equine rhinopneumonitis. AB - Bovine herpesvirus 1247 (one dose) was given subcutaneously to five pregnant pony mares between 227 and 319 days of their gestations. There were no adverse clinical reactions, and the virus was not recovered from nasal swabs collected during a 2-week period after vaccination. Four ponies foaled full-term, live, healthy foals. The foal of the fifth mare (No. 1) was found dead, but on the basis of the pathologic and virologic examinations, the virus was not considered to be the cause of the death. At 3 weeks after vaccination, the pregnant pony mares had a 13- to 250-fold increase in serum antibody titer to equine herpesvirus-1. A virulent-virus challenge exposure of all pony mares at 208 days after vaccination resulted in antibody titers greater than those just before this exposure. Virus was recovered from nasal swabs from vaccinated mares only on postexposure day 1, whereas the one control (nonvaccinated) pony shed virus for at least 3 days after challenge exposure. The immunogenic and the nonabortifacient characteristics of the herpesvirus 1247 in pregnant pony mares indicate that it may be useful to vaccinate horses against equine herpesvirus-1. PMID- 6254413 TI - Respiratory distress syndrome from lymphangiography contrast medium. AB - Adult respiratory distress syndrome (ARDS) has been reported as a rare complication of lymphangiography with ethiodized oil. We report 2 patients who developed otherwise unexplained pulmonary edema after lymphangiography, and describe an animal model of pulmonary injury after an injection of ethiodized oil. We injected 0.25 ml/kg of body weight intravenously into 45 rabbits, and followed arterial blood gases and/or killed the rabbits randomly at various intervals for morphologic lung examination by light and electron microscopy. Within 24 h after injection, there was moderate hypoxemia from oil embolization, but only minimal lung edema. However, by 2 to 4 days after injections, hypoxemia was most severe and was accompanied by extensive alveolar and interstitial inflammation, hemorrhage, and edema. After 4 days, there was gradual blood gas and morphologic recovery, with complete restoration of normal anatomy by 6 wk. Our data showed that in rabbits, ethiodized oil can reproducibly cause delayed, severe pulmonary injury, thus supporting the clinical reports that ARDS may occur several days after lymphangiography. PMID- 6254414 TI - Reduced granulocyte response to isoproterenol, histamine, and prostaglandin E1 after in vitro incubation with Rhinovirus 16. AB - Rhinovirus respiratory infections have been frequently associated with the precipitation of an asthma attack. As an explanation for virus-provoked asthma, it has been proposed that viruses or their products may alter beta-adrenergic responsiveness. Isolated human granulocytes have provided an in vitro study model for this problem. Granulocyte release of the lysosomal enzyme beta-glucuronidase (BG) occurred after incubation with complement-activated zymosan particles, and this release was inhibited by isoproterenol (ISO), histamine (HIS) acting via its H2 receptor, and prostaglandin E1 (PGE1). In asthma, the granulocyte response to HIS and ISO was impaired, and the ISO impairment was accentuated during virus provoked asthma. After an in vitro incubation of polymorphonuclear leukocytes (PMN) with rhinovirus 16, the granulocyte response to ISO, HIS, and PGE1 was significantly reduced. This change in agonist response was proportional to the virus dosage, maximal at 37 degrees C and after a 60-min incubation period, and occurred with heat or UV-inactivated virus. It is possible that impaired beta adrenergic responsiveness may also develop in other tissues, such as the airway smooth muscle, and thus explain, in part, wheezing during viral respiratory infections. PMID- 6254415 TI - An outbreak of varicella-zoster virus infection among cancer patients. AB - An outbreak of varicella-zoster infection occurred among patients of the Medicine Branch, National Cancer Institute, National Institutes of Health. Epidemiologic investigation suggested that the outbreak was due to two distinct types of disease. One type was acquired without previous exposure to other diseased patients and invariably associated with dermatomal lesions. The other, an a typical form, was associated with person-to-person transmission and equivocal initial dermatomal distribution and had an incubation period of approximately 11 to 25 days. Despite the diagnosis of zoster, the latter probably was varicella, occurring in patients who were immunodeficient because of disease, debility, and chemotherapy. PMID- 6254416 TI - Malignant glucagonoma syndrome: response to chemotherapy. AB - A 58-year-old white woman with known metastatic glucagonoma had widespread necrolytic migratory erythema characteristic of the glucagonoma syndrome. She did not respond to conventional chemotherapy with streptozocin. After one course of dacarbazine therapy, she had remission of the glucagonoma clinically with regression of tumor metastases as defined by liver scanning. After 10 months and additional courses of dacarbazine therapy, she remains in clinical remission. Plasma glucagon levels have decreased although they remain at two to four times the upper limit of normal. On several occasions there was resolution of this patient's rash after intravenous glucose in the absence of supplemental amino acids. We conclude that dacarbazine is an effective mode of chemotherapy for malignant glucagonoma. PMID- 6254417 TI - Influenza vaccine 1980--1981. Recommendation of the Public Health Service Immunization Practices Advisory Committee, Center for Disease Control, Department of Health and Human Services; Atlanta, Georgia. AB - This annual revision of influenza vaccine recommendations updates information on influenza activity in the United States during 1979--1980 and provides information on the vaccine to be available for the 1980--1981 influenza season. PMID- 6254418 TI - Oxygen metabolism and the toxic properties of phagocytes. AB - The products of oxygen reduction (superoxide anion, hydrogen peroxide, hydroxyl radicals) and excitation (singlet oxygen) have been implicated in the toxic properties of phagocytes (neutrophils, eosinophils, and mononuclear phagocytes). Enzymes that potentiate (such as peroxidase) or limit (such as catalase, superoxide dismutase) the toxicity of these agents contribute to the complexity of the oxygen-dependent antimicrobial systems of phagocytes. These toxic systems are dormant when the phagocyte is at rest but are activated when the need arises and directed to the destruction of invading microorganisms and other foreign cells. Occasionally, the toxic systems are directed against normal host cells and in this way contribute to the pathogenesis of disease. PMID- 6254419 TI - [Study of the metabolism of fatty acids and total plasma lipids, and platelet aggregation of a population of elderly men using a diet enriched in gamma linolenic acid]. AB - 33 healthy men, 72 years old on average, ingested during five week: 2,4 g of Oenothera Biennis oil rich in PUFA. Before and after ingestion, platelet aggregation was measured according to the Born's photometric method, which divided the original group into two classes: "15" normal subjects (NAG) and "18" hyperagregated (HAG). The fatty acids contained in the serum were analysed by GLC. NAG liquid pattern did not show any difference after oil ingestion, as in HAG group, significant modifications were observed in palmitoleic, linoleic and linolenic fatty acid series. These observations probably correspond to a fundamental behavior difference, which might be related to desaturase activity reduction. Such a phenomenon would appear with ageing in some subjects. If this hypothesis is confirmed, the inclusion of the two methods of investigation described above would constitute a good approach for studying the enzymatic system activity in ageing. PMID- 6254420 TI - [Protective effect of alpha-linolenic acid in encephalomalacia in chickens]. AB - Encephalomacia is a vitamin E deficiency syndrome which affects the cerebellum of young chicks. The lesion includes degenerative alterations of cellular and fibrillar elements, apparently as the result of the ischaemia caused by thrombotic events in the microvascular system. A supply of linoleic acid, as fatty acid methyl esters prepared from safflower oil (Carthamus tinctorius), caused a high incidence of encephalomalacia. On the other hand, linseed oil esters, rich in alpha-linolenic acid, did not induce any symptoms and protected the chicks to a large extend against the development of signs produced by linoleic acid. Fatty acid esters of cod liver oil, rich in long-chain derivatives of alpha-linolenic acid, exerted a relatively weak protective effect. The analytical results show that a supply of alpha-linolenic acid led to an accumulation of eicosapentaenoic acid, 20:5 omega 3, and a reduced concentration of arachidonic acid in the phospholipds of liver and plasma. The results suggest that, under the conditions leading to encephalomalacia, the prostacyclin thromboxane balance is shifted in direction of an excessive production of TXA2, causing thrombus formation in the capillaries of the cerebellum, alpha-linolenic acid, by modifying the PUFA profile, exerts a multiple action the main result of which appears to be an antithrombotic effect at the level of the microvascular system of the cerebellum. PMID- 6254422 TI - [Effects of a dietary deficiency of alpha-linolenic acid in the rat]. PMID- 6254421 TI - [Membrane polyunsaturated fatty acids of mammalian nerve cells in culture]. AB - We have observed some important changes in the distribution of fatty acid classes in cultured nerve cells according to the normal or tumoral origin of the cells: normal cells exhibit higher levels of polyunsaturated fatty acids and lower levels of monounsaturated fatty acids than tumoral cells do. When the culture medium of neuroblastoma cells is supplemented with polyunsaturated fatty acids, these fatty acids are incorporated into membrane phospholipids and some specific alterations of membrane functions occur: modification of the kinetic parameters of ecto-enzyme activities, modification of amino-acid transport characteristics. A brief review of the literature shows that polyunsaturated fatty acids are not essential for cell life in vitro, provided that monounsaturated fatty acids can be present in the cells. Polyunsaturated fatty acids seem therefore play only a regulatory role of some membrane functions. PMID- 6254423 TI - Research findings on the toxicity of quartz particles relevant to pulverized fuel ash. PMID- 6254424 TI - Simultaneous determination of 2,4- and 2,6-diisocyanatotoluene (TDI) and 3,3' dichloro-4,4'-diaminodiphenylmethane (MOCA) in air. PMID- 6254425 TI - [Two cases of cervical extra-articular synovialosarcoma (author's transl)]. PMID- 6254426 TI - Relationship between condylomata and laryngeal papillomata. Clinical and molecular virological evidence. AB - In a survey of 49 papilloma patients accurate maternal condyloma history was obtained in 31 instances and of these, 21 were positive for the presence of condyloma during pregnancy or parturition. Molecular virological studies indicate that positive hybridization could be demonstrated to human papilloma virus 2 in both laryngeal papilloma and condyloma by the Southern blot technique. Immunoperoxidase staining illustrated the presence of virus-related particles only near the surface of the mucous membrane papilloma, which is in contrast to the definite staining of the stratum granulosum and stratum corneum of verrucae. Collectively this provides convincing evidence for an etiological relationship between condyloma acuminata and some laryngeal papillomata. The highly contagious nature of human papilloma virus infection is discussed and the possibility of cesarian section in the presence of active condyloma must be considered. PMID- 6254427 TI - [Epidermodysplasia verruciformis (2 cases). Immunological study (author's transl)]. AB - Flat wart-like lesions of two patients with epidermodysplasia verruciformis (EDV) were associated with pink, tan or depigmented pityriasis-like macules. There was no familial history nor mental retardation. Human papilloma virus (HPV) type 5 was demonstrated in the two patients and was responsible for the pityriasis-like lesions. Malignancies seem to be closely related to HPV-5 infection since bowenoid transformation occurred in the 2 patients. Immunological studies showed an increase of serum IgE in both patients and an important decrease of IgM in one of them. Most of delayed hypersensitivity skin tests were negative. T-cell percentages (E rosettes) were decreased in one patient, normal for the other one. The mitogenic response to PHA and ConA was markedly depressed in the two patients but returned to normal values in one of them after 3 months of aromatic retinoid (Ro 10-9359) treatment. Beside the viral type, the defect of cell mediated immunity could play an important role in the disease and in the malignant conversion of the lesions. A long-term preventive treatment by retinoic acid derivatives could be of interest for patients with HPV type 5 EDV. PMID- 6254429 TI - Foot and mouth disease virus. Properties of a clone selected by terminal dilution technique from the original population. AB - Using the terminal dilution technique, a cloned virus was selected in a tissue culture systems from a heterogenous population of the original virus. The different markers studied differentiated the cloned virus from the original virus on the basis of its following characters: 1. ability to grow more efficiently at 29 than at 37 degrees C. 2. unstability of its capsid as seen by: a. high degree of sensitivity to heating at 50 degrees C for 10 min of exposure to pH 6.4 for 10 min. b. more inactivation by overnight exposure to 37 and 4 degrees C. 3. late pathogenicity in the suckling mice. The practical usefulness of a simple technique of the selection of viral clones and the possibilities of such clones to be used in the liver (modified) vaccine are discussed. PMID- 6254428 TI - [Granuloma gluteale infantum: ultrastructural study (author's transl)]. AB - Intracytoplasmic structures resembling rickettsia-like bodies are observed in the dermal macrophages of a case of granuloma gluteale infantum. The cells which contained these bodies show severe necrotic changes. No yeast and nor crystalline structures were observed in the dermal infiltrate. The relevance of these observations is discussed. PMID- 6254430 TI - Immunogenicity studies of foot and mouth disease vaccines at different concentrations of antigen and saponin. AB - Frenkel-type monovalent O1 and C vaccines were tested for immunogenicity under field conditions, in a large cattle farm. Both vaccines were applied in four dilutions, to furnish different concentrations of antigen, and each dilution was tested with 4 and 8 mg/dose levels of saponin, and without adjuvant. In adult multivaccinated already one eight of the standard bovine dose of both preparations developed a satisfactory booster effect, and presence or absence of the adjuvant played little role. In the growing (5-7 months old) primary vaccinated immune response to vaccination depended on the applied dose of antigen; the higher the latter, the firmer immunity was developed. The immunogenicity-enhancing effect of saponin, too, was more pronounced in the young than in the adult vaccinated. The result of the immunization was significantly improved by the use of 8 mg saponin per dose, compared to that found with 4 mg or no adjuvant in the vaccine. The best vaccination results were obtained on combination on the highest antigen conentrations with 8 mg saponin/dose. The type O1 antigen proved to be about half as strong, as the type C one, having elicited the same degree of immunity as C in a roughly double dose. PMID- 6254431 TI - Isolation of pig rotavirus in France. Identification and experimental infections. AB - Rotavirus had been demonstrated in France, in diarrheic pig faeces by electron microscopy and ELISA. Field isolates were pathogenic for HD piglets and antigenically related to american OSU rotavirus as demonstrated by protective feedings experiments. PMID- 6254432 TI - [Granular cell tumor of the esophagus: Abrikosov's tumor (author's transl)]. PMID- 6254433 TI - Viral and bacterial antibody responses in multiple sclerosis. AB - An imprint electroimmunofixation method (IEIF) was used to characterize antibodies to eight viral antigens (measles, mumps, rubella, herpes simplex type 1, varicella-zoster, vaccinia, cytomegalovirus, adenovirus) and four bacterial antigens (beta-hemolytic streptococcus, Hemophilus influenzae type B, Escherichia coli, enterococcus) in serum and cerebrospinal fluid (CSF) of 12 patients with multiple sclerosis (MS). Twelve patients matched for age and sex sex served as controls. Evidence for intrathecal synthesis of oligoclonal antibodies to one or more antigens was found in all 12 MS patients and in 1 of the controls. In the MS group, antibodies to viruses with neurotropic properties were more frequently associated with local synthesis than antibodies to other viruses and bacteria. The types and number of locally synthesized antibodies showed no correlation with disease duration and severity. The antibodies were not associated with oligoclonal CSF IgG and appear to account for only a minor fraction of the locally synthesized CSF IgG in MS. PMID- 6254434 TI - Reduced enzyme activities in inherited ataxia. PMID- 6254435 TI - Changes in endoneurial fluid pressure, permeability, and peripheral nerve ultrastructure in experimental lead neuropathy. AB - The dynamics of endoneurial edema were studied by quantifying endoneurial fluid pressure (EFP) during the development of lead neuropathy and correlating these data with changes in blood-nerve barrier permeability and with morphological alterations in nerves, capillaries, and Schwann cells. EFP measured from the sciatic nerve in control Long-Evans rats was 2.1 +/- 1.0 cm H2O. EFP was significantly elevated 7 weeks after animals were started on a diet containing 6% lead carbonate, and it increased progressively until a plateau in pressure was reached between weeks 9 and 11. Thereafter, EFP gradually returned to normal values. The progressive increase in EFP was highly correlated with the extravasation of osmotically active macromolecules, traced by fluorescein isothiocyanate-dextran compounds of graded molecular weight and by horseradish peroxidase (HRP). Electron microscopy revealed extravasation of HRP between endothelial cells, intranuclear inclusions characteristic of lead poisoning in Schwann cell nuclei, demyelination, and remyelination. The observation of intranuclear inclusions consistent with lead deposition in Schwann cells strengthens the hypothesis that extravasated lead in the interstitial fluid causes direct injury to Schwann cells, giving rise to demyelination. Nerve compliance was determined. PMID- 6254436 TI - Lafora disease: diagnosis by liver biopsy. AB - We have studied four patients who had a clinical course compatible with Lafora disease. The diagnosis was confirmed in one by the presence of Lafora bodies in central nervous system neurons at autopsy and was supported in another by findings in the cerebral biopsy of a sibling. Our patients had no clinically apparent liver disease, but liver specimens in each instance showed a distinctive histological abnormality, with hepatocytes containing inclusions having a ground glass appearance. The liver biopsy findings appear to be relatively specific for this disorder and can easily be differentiated from those in other liver diseases. PMID- 6254437 TI - Acute autonomic and sensory neuropathy. AB - A previously well 9-year-old boy developed acute autonomic and sensory neuropathy. Recovery was incomplete over a thirteen-month period. Spinal fluid protein was increased during the acute phase. Sensory nerve potentials were absent in the presence of normal motor and mixed nerve conduction velocities. Sural nerve biopsy revealed marked axonal degeneration of myelinated as well as unmyelinated fibers. This case represents a widespread acute ganglionopathy of unknown cause. PMID- 6254438 TI - C-6 glioma growth in rats: suppression with a beta-adrenergic agonist and a phosphodiesterase inhibitor. AB - Rat C-6 glioma possesses a beta-adrenergic receptor which, when activated, raises intracellular levels of cyclic adenosine monophosphate (cAMP) in cultured C-6 glioma cells. The present study shows that growth of C-6 glioma is suppressed in rats treated with the beta-adrenergic agonist isoproterenol. Addition of papaverine, a cAMP phosphodiesterase inhibitor, to the treatment schedule augments this effect. Pharmacological agents that elevate intracellular cAMP levels may retard the growth of neural tumors in vivo. PMID- 6254439 TI - Sustained limbic seizures induced by intraamygdaloid kainic acid in the baboon: Symptomatology and neuropathological consequences. AB - In Papio papio baboons chronically prepared for cortical and deep electroencephalographic recording, injection of kainic acid into the amygdala (7 animals) or temporal pole (2 animals) gave rise to focal epileptic discharges lasting 15 to 150 hours. Electrographically, the seizure activity spread ipsilaterally and contralaterally within the limbic system but did not become generalized. The principal associated motor signs were arrest of movement and oral automatisms. Histological examination after two to ten days demonstrated lesions (neuron loss and gliosis) at the injection site that varied according to the amount of kainic acid injected (2 to 68 microgram). "Remote" lesions occurred in the ipsilateral hippocampus (end-folium and Sommer sector) and neocortex (occipital and frontal regions). The hippocampal lesions were comparable to those previously described as consequent to status epilepticus. PMID- 6254440 TI - Lymph nodes--a possible site for sympathetic neuronal regulation of immune responses. AB - Noradrenergic fibers were identified in rat cervical lymph nodes by fluorescence histochemistry and confirmed by radioenzymatic determination of norepinephrine. After superior cervical ganglionectomy, lymph node norepinephrine and noradrenergic fluorescence were strikingly decreased. The alpha-adrenergic radioligand [3H] dihydroergocryptine bound to saturable sites on lymph node membranes (0.20 pmol/mg protein; affinity constant, 8 nM) with characteristics expected for alpha-adrenergic receptor binding. The alpha-adrenergic binding sites were present in high concentration in membranes from lymph node stroma but were negligible in membranes of lymphocytes teased from nodes. In lymph nodes the ratio of alpha-adrenergic binding sites to norepinephrine content was higher than ratios of many other sympathetically innervated tissues such as iris or vas deferens. The presence of sympathetic innervation and the high concentration of alpha-adrenergic binding sites relative to that innervation suggest that the sympathetic nervous system modulates an intrinsic lymph node function through alpha-adrenergic mechanisms. PMID- 6254441 TI - Proteins of the outer membrane of gram-negative bacteria. PMID- 6254442 TI - Flagellar structure and function in eubacteria. PMID- 6254443 TI - Proton movements across the membranes of sarcoplasmic reticulum during the uptake of calcium ions. PMID- 6254444 TI - Dietary fibre in under- and overnutrition in childhood. AB - Children in developing countries pass stools that are very different from those passed by children in Europe. These stools reflect a diet of unrefined carbohydrate with low-energy density, and which due to the large volume results in an energy deficit in the child. This energy deficit is now considered to be the major cause of the almost universal undernutrition. Much of the improved health in European children during the last century has probably arisen through better nutrition due to more-refined carbohydrates and to more fat in the diet. Over the same period as children have become healthier, diseases of civilisation have appeared. One factor in such diseases is clearly that of diet, and these diseases may partly be caused by the high-energy density and the low-dietary fibre content. Changes in diet offer the greatest hope for a rapid improvement in health. In the developing world we need to find a means for making foods with a high-energy density more easily available to overcome the undernutrition in childhood. In industrialised countries older children need to become accustomed to a diet of lower-energy than at present, containing more unrefined carbohydrate and less fat. PMID- 6254445 TI - Role of viruses in febrile convulsions. PMID- 6254446 TI - Infantile spasms syndrome in monozygotic twins. AB - The infantile spasms syndrome appeared on the same day in a pair of monozygotic twins at age 6 months. Clinical, electroencephalographic, and neuroradiological findings during the development of the disease are reported. One of the twins was treated with ACTH and in his case clinical and electroencephalographic improvement was more rapid than in the other who was treated with clonazepam. While the computer tomography scan initially showed in each twin an area of low density in the right fronto-parietal region, this had disappeared in the tomograms obtained about 8 months later. PMID- 6254447 TI - Oral rehydration therapy for treatment of rotavirus diarrhoea in a rural treatment centre in Bangladesh. AB - In November 1977, an enzyme-linked immunosorbent assay for detecting rotavirus antigen was introduced in the laboratory of a rural treatment centre in Bangladesh. During the next 40 days rotavirus without other pathogens was found in the stools of 216 (45%) of 480 children under age 5 years who visited the centre with a gastrointestinal illness. 188 (87%) of these children were treated with oral rehydration alone, using the solution currently recommended by the World Health Organisation, while 28 (13%) also required some intravenous rehydration; there were no deaths. Oral rehydration treatment was judged successful in 205 (95%) of the rotavirus patients and was not associated with any serious side effects. Oral rehydration treatment, with this solution, has been used extensively and successfully in the treatment of enterotoxin-mediated diarrhoea and can also safely be used for treating rotavirus diarrhoea in infants and young children. PMID- 6254448 TI - Antiglobulin antibody in the sera of contacts of children with leukaemia. AB - Healthy adults (parents, neighbours, and hospital staff) in close contact with children with leukaemia were found to have a high incidence of positive latex agglutination antiglobulin tests (probably an IgM antiglobulin antibody). This may explain a previous report of a high incidence of IgM anti-EB virus antibodies in parents of leukaemic children, which our results did not confirm (IgM antiglobulin, reacting with IgG anti-EB virus, could have been misinterpreted as IgM anti-EB virus). The antiglobulin antibody probably represents a nonspecific response to an infective agent. Other hospital staff, including those exposed to nonleukaemic children with infections, had a much lower incidence of the antibody, and it may represent a response to the leukaemic process itself, rather than to the infections to which such children are prone. Some leukaemic children have a similar antibody. PMID- 6254449 TI - Outbreaks of hand, foot, and mouth disease by enterovirus 71. High incidence of complication disorders of central nervous system. AB - In Japan we have had two outbreaks of hand, foot, and mouth disease associated with disorders of the central nervous system, one in 1973 and the other in 1978. The isolated virus in both outbreaks was enterovirus 71. Central nervous system disorders were present in 24% of patients in 1973 and in 8% of patients in 1978. These disorders were localised encephalitis with cerebellar signs as the main feature, aseptic meningitis, and polio-like paresis. The enterovirus 71 isolated in Japan had strong dermatotropic as well as neurotropic tendencies. However in cross-neutralisation tests, no difference in antigenicity from the prototype, BrCr strain, was recognised. PMID- 6254450 TI - ACTH therapy in infantile spasms: side effects. AB - 162 children with infantile spasms were treated with ACTH at the Children's Hospital, Helsinki, and at the Aurora Hospital, Helsinki, during 1960--76. In a large proportion (37%) of the children the treatment caused pronounced side effects, and the mortality was 4.9%. The most common complications were infections: septic infections, pneumonias, and urinary and gastrointestinal infections. Other side effects were arterial hypertension (11), osteoporosis (2), hypokalaemic alkalosis (2), and other marked electrolyte disturbances (10). In children necropsy showed fresh intracerebral haemorrhages. Four children developed oliguria and hyperkalaemia during and after withdrawal of ACTH. One of them had tubular necrosis confirmed by renal biopsy. Infections were significantly more common with large doses (120 units) of ACTH than with small ones (40 units). It is concluded that side effects, even severe ones, are more common during treatment than had been assumed. Careful watch is important before and after treatment. The benefit of very high dosages should also be reconsidered. PMID- 6254451 TI - Blood platelet cyclic AMP during long-term treatment of premature labor. AB - The mean platelet cyclic AMP (cAMP) value in normal pregnant women between 20 and 37 weeks of gestation was 8.2 +/- 0.4 (SEM) pmol cAMP/10(9) platelets (n = 100). From 35 patients with premature labor, 81 blood samples were obtained from measurement of the platelet cAMP before, during and after treatment with fenoterol/verapamil. During the first 4 days of therapy there was an increase of cAMP (p < 0.005); with long-term therapy the blood platelet cAMP was decreased (p < 0.005). Because platelet aggregation has a negative correlation with platelet cAMP, fenoterol should be used cautiously in patients with defective platelet function, in severe bleeding, and before surgery. With long-term treatment platelet aggregation may be increased and thus contribute to the formation of thrombi. Placental perfusion is not likely to be improved by increased platelet aggregation during long-term treatment with fenoterol. PMID- 6254452 TI - The influence of high doses of oral medroxyprogesterone acetate on glucose tolerance, serum insulin levels and adrenal response to ACTH. A study of 17 patients under treatment for endometrial cancer. AB - Seventeen women aged 55 to 76 years who had been treated for endometrial cancer by surgery or radiotherapy or a combination of both were given 300 mg of medroxyprogesterone acetate (MPA) daily by mouth. Before treatment and again during the 3rd week of treatment an oral glucose tolerance test (with measurement of serum insulin levels) and an ACTH-stimulation test were done. All blood glucose levels tended to be higher with MOA therapy and serum insulin levels were significantly increased 3 h after a glucose load. The rise of serum cortisol 30 min after ACTH-stimulation was significantly less with MPA therapy. Oral MPA thus appeared to have a glucocorticoid-like action. PMID- 6254453 TI - The experimental chemotherapy of leishmaniasis, IV. The development of a rodent model for visceral infection. AB - A description is given of two methods for investigating the action of drugs against a viscerotropic Leishmania in mice. The parasite employed was isolated from a patient with kala-azar in Ethiopia. It is designated 'L. infantum LV9' and produces a visceral infection in NMRI mice. The biochemical typing characters of the parasite are described. In Method A, infected animals were treated from the 5th or 6th day after infection (D + 5 or D + 6) for five consecutive days. They were sacrificed 24 hours after the completion of drug treatment and an estimate was made of the amastigote load in the liver. A comparison of this with untreated controls gives an index of activity of a test drug, from 0 to 3. Method B is similar except that the ED50 and ED90 are determined by graphic analysis of data from graded drug doses. A comparison is made with sodium stibogluconate used as a positive drug control to yield a 'Pentostam Index'. The course of infection in BALB/c and NMRI mice is compared with that in random-bred Swiss mice in which 'L. infantum LV9' produces an inconsistent infection. An inoculum of 10(7) amastigotes produces a peak parasite intensity between D + 15 and D + 20. The ED50 and ED90 of sodium stibogluconate (Pentostam) (as Sbv) in Method B are 22 x 5 and 46 x 5 mg/kg sc daily x 5. (By Method A the single dose figures are 65 and 280 mg/kg.) For routine use a standard dose level of 120 mg/kg sc daily x 5 of Pentostam (Sbv) is used in Method B. The ED50 and ED90 of meglumine antimoniate (Glucantime) (as Sbv) in Method B are 11 x 6 and 66 x 7 mg/kg sc daily x 5. Data are given for other antimonials in Method A. Pentamidine and diminazene aceturate proved to have a slow action which was more readily demonstrated if the observation period was prolonged. Amphotericin B was moderately active but toxic to the host. The relevance of these models and a comparison of data found in the mouse and hamster are debated. PMID- 6254454 TI - Modulation of FSH action by inhibin. AB - Both testicular and ovarian inhibin preparations caused a dose-related inhibition of binding of 125I-hFSH to rat testicular receptors. Testicular inhibin also suppressed the FSH-induced production of cAMP by rats testis in vitro. These data demonstrate a direct action of inhibin at the testicular level by interfering with FSH action. PMID- 6254455 TI - Alpha adrenergic receptors in beef aortic membranes characterised by [3H] dihydroergocryptine binding. AB - Alpha adrenergic receptors of beef vascular smooth muscle membranes were identified and characterised using [3H] dihydroergocryptine as a radioligand. Under our experimental conditions [3H] dihydroergocryptine binds rapidly and in saturable fashion to isolated beef aortic membranes, specific binding reaching equilibrium in 5 min at 37 degrees C. Scatchard analysis of the binding data indicates a single population of binding sites with the dissociation constant of 10.4 nM and maximum number of binding sites equaling 156 fmol/mg of membrane protein. The identity of [3H] dihydroergocryptine binding sites with the alpha receptor was established by the competition studies. Catecholamines inhibited binding in the following order: (-) epinephrine > (-) norepinephrine > (+/-) norepinephrine > (-) isoproterenol. Alpha adrenergic antagonists (prazosin, phentolamine, ergotamine, dihydroergocryptine, yohimbine) are potent inhibitors of binding whereas the beta adrenergic antagonist propranolol showed a weak affinity for the binding sites. These results suggest that the high affinity [3H] dihydroergocryptine binding sites are identical to the vascular (alpha 1) adrenergic receptor. PMID- 6254456 TI - Antiemetic effect of tetrahydrocannabinol. Compared with placebo and prochlorperazine in chemotherapy-associated nausea and emesis. AB - Fifty-five patients harboring a variety of neoplasms and previously found to have severe nausea or emesis from antitumor drugs were given antiemetic prophylaxis in a double-blind, randomized, crossover fashion. Tetrahydrocannabinol (THC), prochlorperazine, and placebo were compared. Nausea was absent in 40 of 55 patients receiving THC, eight of 55 patients receiving prochlorperazine, and five of 55 in the placebo group. The antiemetic effect of THC appeared to be more efficacious for cyclophosphamide, fluorouracil, and doxorubicin hydrochloride, and less so for mechlorethamine hydrochloride and the nitrosureas. Tetrahydrocannabinol appears to offer significant control of nausea in most patients and exceeding by far that provided by prochlorperazine. PMID- 6254457 TI - A trial of vidarabine for cytomegalovirus infection in renal transplant patients. AB - Vidarabine was evaluated in renal transplant patients as a potential therapeutic agent in cytomegalovirus (CMV) infection. Four patients received vidarabine on an open protocol, then ten additional patients were enrolled in a double-blind protocol. Among the nine patients who received vidarabine, no notable clinical improvement occurred in either the vidarabine- or placebo-treated groups. Thus, vidarabine showed no therapeutic effect in the treatment of CMV infections at the dosages used. Four patients showed dramatic CNS deterioration within several days of the onset of vidarabine therapy. Tremors and myoclonus were common, and one patient had unusual brain pathologic changes with widespread neuronal chromatolysis. The pathologic findings in the brain in the other three patients were complex and included intracerebral hemorrhage, Fabry's disease, coccidioidomycosis meningitis, and cerebral vascular occlusion. Thus, there was no conclusive proof that vidarabine contributed to the sudden neurologic deterioration of these patients. PMID- 6254458 TI - Idiopathic lower esophageal sphincter incompetence and esophageal stricture. PMID- 6254459 TI - Cyclic adenosine 3',5'-monophosphate and germination of sporangiospores from the fungus Mucor. AB - Cyclic adenosine 3',5'-monophosphate (cAMP) metabolism was examined in germinating sporangiospores of Mucor genevensis and Mucor mucedo. Exogenous cAMP prevented normal hyphal development from sporangiospores. Internal pools of cAMP fluctuated profoundly during development. Spherical growth of the spores was characterized by large pools of cAMP whereas germ tube emergence and hyphal elongation were characterized by small pools of cAMP. These observations suggest a possible role for cAMP in sporangiospore germination. Adenylate cyclase activities fluctuated significantly during germination with maximum values attained during spherical growth. In contrast, cAMP phosphodiesterase activities remained constant throughout germination. Internal cAMP levels may therefore be regulated by adjustment of adenylate cyclase activities. The binding of cAMP by soluble cell proteins was measured. cAMP-binding activity changed greatly during germination. Dormant and spherically growing spores possessed the highest activities. Developing hyphae contained the lowest activities. Use of the photoaffinity label, 8-azido-[32P]cAMP, in conjunction with sodium dodecyl sulfate-polyacrylamide-gel electrophoresis allowed the identification of a small population of morphogenetic-stage-specific proteins which bind cAMP and may be of regulatory significance to development. PMID- 6254460 TI - [Peripheral neuropathy and chronic cholestasis due to paucity of interlobular bile ducts (author's transl)]. AB - Peripheral neuropathy was observed in three patients in the course of a chronic cholestasis due to paucity of interlobular bile ducts associated with several malformations (Alagille's syndrome). In two patients, investigations showed a chronic axonal neuropathy. In a third, the low density of myelinated fibers was associated with onion-bulb proliferation on the Schwann-cells and myelin abnormalities related to an associated dominant inherited primary hypertrophic neuropathy. The responsibility of a chronic vitamin E deficiency in the development of axonal lesions is discussed. PMID- 6254461 TI - [Two viruses]. PMID- 6254462 TI - Ubiquity of natural antibodies to the mammary tumour virus in mice. AB - Sera of female and male mice from eleven inbred mouse strains collected at either 4, 12, 36 or 60 weeks of age were tested for the presence of natural antibodies to the murine mammary tumour virus by means of the Sepharose bead immunofluorescence assay. Antibodies to the virus proved to be ubiquitous, but pronounced strain differences were found in titer and onset of antibody production. These differences were related to neither release of virus in the milk nor susceptibility to spontaneous mammary tumour development of a given strain. Immunological specificity of the observed reactions was concluded from a) the failure to block the reaction by absorption with fetal calf serum, mouse milk or sheep erythrocytes, while absorption with purified virus abolished the reactivity; b) the lack of reactivity of rat sera with the mouse mammary tumour virus in this system; c) the negative response of mouse sera with Sepharose beads coated with ovalbumin; d) the lack of correlation between antibody titers to Rauscher murine leukemia virus and mammary tumour virus in this system; e) the retaining of activity to highly purified viral polypeptides; f) blocking of the reaction by preincubation with rabbit anti-mouse immunoglobulin serum or Protein A from Staphylococcus aureus. Since germfree mice of various strains also have such antibodies, it is concluded that the reactions are not due to horizontal transmission of the virus. From the lack of correlation between antibody titers and tumour incidences, it is concluded that various systems overshadow the potential immunosurveillance role of such natural antiviral antibodies. PMID- 6254463 TI - Abelson murine leukemia virus: characterization of a polyprotein containing phosphorylated component(s) encoded by newly acquired sequences. AB - A previously described 120,000 dalton polyprotein, P120, encoded by the Abelson strain of murine leukemia virus (AbLV) is compared to translational products representing the entire Moloney murine leukemia virus (MuLV) genome. Each of three [35S]-methionine tryptic present in Moloney-MuLV Pr65gag are also represented in Pr180gag-pol. Of these, one peptide corresponding to Moloney-MuLV p12, but neither of two p30 specific peptides are present in AbLV P120. None of the twelve remaining methionine containing peptides present in AbLV P120 appear to correspond to those of either Moloney-MuLV Pr82env. AbLV P120 and a 110,000 dalton polyprotein encoded by a second transforming isolate of mouse origin, designated AK-T8, are both shown to be highly phosphorylated. Sites of phosphorylation included known phosphorylated structural (p12) components, as well as components encoded by acquired cellular sequences. Immunoprecipitates of AbLV P120 obtained from either cells or pseudotype virions are shown to contain protein kinase activity which recognizes AbLv P120 as substrate. This activity may represent an intrinsic property of the polyprotein itself or represent a cellular enzyme associated with AbLV P120 in the form of an enzyme-substrate complex. PMID- 6254464 TI - Immunological reactivity in patients with widespread carcinoma of the liver and bile ducts as evaluated on the basis of spleen white pulp morphology. AB - The morphology of the white pulp of the spleens collected from forty four patients died in widespread carcinoma of the liver and extrahepatic bile ducts was histologically evaluated by utilizing the standardized reporting system previously outlined. As a control material, the same number of age- and sex matched patients died in myocardial infarction or cerebrovascular accident without signs of any malignancy was used. Special attention was paid to the assessment of the T- and B-lymphocyte populations responsible for the immunological reactivity. Histological characteristics suggesting an active function of both the cell-mediated and humoral immune reactions (central and peripheral lymphoid sheats, respectively) were found to be within the normal range in the control spleens, whereas in the cancer series, both these elements were profoundly deranged. The significance of the histological observations made was discussed in the light of the tumor immunology, and a conclusion was drawn that an impairment of both the humoral and cell-mediated immune responses must exist in patients dying in widespread hepato-biliary carcinoma. The applicability of the standardized reporting system used was advocated. PMID- 6254465 TI - [Tumour induction with alkyl-nitrosoureas in ribbed newts (Pleurodeles waltlii) (author's transl)]. AB - A search for animal models in the field of environmental carcinogenesis was performed. 50 adult ribbed newts were exposed to methyl- and ethylnitrosoureas. In 10 animals fibro- and hemangiosarcomas, nephroblastomas and a cavernous hemangioma were induced. No tumors of the nervous system occurred. PMID- 6254466 TI - [Activities of several enzymes of glycolysis and of the glucose shunt in the Albert hepatoma of mouse (author's transl)]. AB - The activities of key enzymes of glycolysis and of the glucose shunt as well as the capacity of lactic acid formation were determined in the high-speed tissue supernatant of the transplantable Albert hepatoma of mouse [originally produced by oral application of chrysoidin (2,4-diaminoazobenzene) on C57 Black mice]. Furthermore, the particle-bound hexokinase activity was determined. The following results were obtained: In the hepatoma the activities of aldolase, pyruvate kinase and lactic dehydrogenase are hardly altered compared with normal liver. The activities of hexokinase and phosphofructokinase are increased 2,5-fold, those of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase 2 fold. The capacity for lactic acid formation from glucose is 7 times as high in the hepatoma supernatant. Strong differences emerge from the liver-to-hepatoma relationship in terms of intracellular distribution of the hexokinase (total homogenate 1 : 5, supernatant 1 : 2,5 and particle-bound hexokinase activity 1 : 18). A summarizing consideration of all the results obtained so far for the Albert hepatoma shows that this malignoma departss in several biochemical parameters from the "Molecular Correlation Concept" maintained by Weber, providing more evidence for the individuality of tumors. PMID- 6254468 TI - Michaelis-Gutmann bodies. PMID- 6254467 TI - Glioblastoma multiforme with tuberous sclerosis. Report of a case. AB - Gliomas of the CNS associated with tuberous sclerosis have been well documented; malignant degeneration to glioblastoma multiforme, however, is rare. We studied a 17-year-old boy with stigmata of tuberous sclerosis and a cerebral glioblastoma multiforme. The rarity of this occurrence suggests that neoplasms arising from hamartomas may behave differently than those CNS tumors that arise apparently de novo. PMID- 6254469 TI - Collagenase activity of the human aorta. A comparison of patients with and without abdominal aortic aneurysms. AB - Deficit of collagen may be a precipitating cause of aneurysm formation and expansion. Specimens of aneurysmal wall were obtained from 11 patients who underwent aneurysmectomy. Comparison aortic specimens were obtained from five patients who underwent aortofemoral bypass for occlusive disease. Collagenase activity was determined on the particulate and soluble fractions by the liberation of L-leucine, with bovine collagen as the substrate. Collagenase activity was detectable in the abdominal aortic aneurysms (AAAs) but not in atherosclerotic aorta or fascia. Collagenase activity was restricted to the particulate fraction in patients with AAAs, and it correlated with aneurysm size. These data suggest that (1) endogenous collagenolytic activity may be responsible for aneurysmal expansion and rupture and that (2) this enzyme is localized in the aneurysmal wall and is inoperative in arteries affected by atherosclerosis. PMID- 6254470 TI - Hepatic nuclear protein kinases in young rats pretreated with 3 methylcholanthrene. AB - The activities of rat liver nucleolar and nucleoplasmic protein kinases were investigated after administration of a single intraperitoneal (i.p.) dose of 100 mg/kg body weight 3-methylcholanthrene (3-MC). A significant increase was observed in the activities of both the nucleolar and nucleoplasmic protein kinases in the hepatic cells from young rats. The maximum stimulation was evident 24 h after pretreatment with 3-MC. The extent of the maximum activation was distinctly greater in the nucleolar (186%) than in the nucleoplasmic fraction (133% compared with the controls). A second activation of the extranucleolar protein kinase fractions was demonstrated 96 h after 3-MC pretreatment. It is suggested that both kinds of enzymes are involved in the mechanism of the cytochrome P-448-inducing action of 3-MC via stimulating nuclear RNA polymerases. PMID- 6254471 TI - Inactivation of transfective poliovirion RNA by a product or products of the interaction of trace copper with an impurity or impurities in reagent-grade phenol. AB - A search for the cause of the inactivation of the transfectivity of the RNA from poliovirions, in the absence of a protective agent such as L-histidine, revealed that the inactivation is associated with trace contamination with copper and with an impurity or impurities in the phenol used to release the RNA from the poliovirions. Cu2+ and the impurity(ies) interact in vitro to produce a proximate inactivator or inactivators of the RNA. Phenol free or nearly free of active impurity can be prepared by steam distillation. Light is not required for formation or for action of the proximate inactivator. Addition of L-histidine to RNA undergoing inactivation promptly stops the inactivation, probably by taking copper away from the proximate inactivator. PMID- 6254472 TI - Effect of inactivator(s) formed from copper and phenol impurity(ies) on the sedimentation rate of transfective poliovirion RNA. AB - Transfective poliovirion RNA after inactivation by the inactivator or inactivators formed from copper and an impurity or impurities in reagent-grade phenol sediments more heterogeneously and, on the average, more slowly than intact transfective RNA. The data are consistent with the hypothesis that the inactivator causes scission of the viral RNA molecules. PMID- 6254473 TI - Morphological observations of the replication of herpesvirus tamarinus in RL-33 cells. AB - The replication in RL-33 cells (rabbit lung cell line) of herpesvirus tamarinus isolated from cotton-topped marmosets (Saguinus oedipus) was investigated by electron microscopy. In the early stages of infection, ring-shaped and granular structures, and fibrillar materials were recognized in the nucleus. Immature particles were often found in such nuclei. The envelope of the virus was formed by budding through intracytoplasmic membranes, the inner nuclear membrane or the membrane of intracytoplasmic vacuoles. Virus particles which appeared to be budding through the plasma membrane were also observed. Aberrant viral forms were produced by independent budding of both the inner and outer nuclear membranes. The mature particles once enveloped acquired a second envelope by budding through intracytoplasmic double membranes or the outer nuclear membrane. Unusual virus associated structures were observed in the cytoplasm and nucleus. Virus particles appeared to be released by the process of reverse phagocytosis. PMID- 6254474 TI - A new method for the determination of virus specific IgG and IgM antibodies. Brief report. AB - A Latex test has been developed for the detection of virus specific IgG and IgM antibodies. Virus was incubated with serum and the resulting virus-antibody complex harvested. Latex particles sensitized with anti IgG and anti IgM were added and the quantity and type of bound antibody determined. PMID- 6254475 TI - Mouse hepatitis virus strain 3 infection of C57, A/Sn and A/J strain mice and their macrophages. Brief report. AB - Mouse hepatitis virus strain 3 replicated in C57, A/Sn and A/J strain mouse macrophages with the production of a clear cytopathic effect, although only C57 and A/Sn strains of mice were killed with similar MHV3 dilutions. We could not confirm a previous report showing that in vitro cultured macrophages from A/J strain mice were resistant to MHV3 infection. PMID- 6254476 TI - Comparison of indirect hemagglutination and 51chromium release tests for detection of Herpes Simplex Virus type 1 and 2 antibodies in patients with recurrent Herpes infections. AB - Indirect hemagglutination and 51Cr release tests (IHAT and 51-CRT respectively) were compared in patients with recurrent herpes simplex virus (HSV) infections from whom HSV-1 or HSV-2 was isolated. Both tests were equally sensitive and specific in detecting HSV antibodies. However, IHAT was more specific in detecting homologous HSV antibody response in patients with recurrent HSV-2 infections. Past infections with HSV-1 in the patients with dual infections were detected by determining HSV-type specific antibodies by inhibition of IHAT. Cross absorption studies showed that the antibody reactivity measured by the two tests was qualitatively and quantitatively different. Nevertheless, IHAT has been found to be more appropriate test for seroepidemiologic studies of HSV-2 infections because of its specificity, rapidity and less cost, whereas, 51-CRT appears to measure antibodies against recent and more predominant type of infecting HSV. PMID- 6254477 TI - Electron microscopy detection and characterization of viral particles in dog stools. AB - A number of apparently normal dog stool samples, randomly collected on the sidewalks of Paris were examined by Electron Microscopy. The study revealed the presence of viral particles in 27 cases. Morphological criteria lead to the characterization of rotavirus in 2 specimen, coronavirus in 7 and parvovirus in 5. Rotavirus particles appeared always alone while coronavirus and parvovirus particles were present together in 5 cases. Similar particles have been implicated in animal and human gastroenteritis. The importance of their presence in canine dejections is discussed in view of pollution by dog stools of urban and suburban areas. PMID- 6254478 TI - Effects of tocopherol deficiency on lipid metabolism in the arterial wall of rats on normal and high cholesterol diets. AB - The effects of dietary tocopherol deficiency on arterial wall enzymes involved in lipid synthesis and hydrolysis were studied in rats receiving normal diets and diets supplemented with 1% cholesterol. Arterial wall lipase and cholesterol esterase were associated with both the lysosome and microsome fractions, whereas acyl CoA synthetase, triglyceride synthesizing activity, cholesteryl ester synthesizing activity and cytidine diphosphatecholine-1,2-diacyl glycerol choline phosphotransferase (CPT) were found mainly in the microsomal fraction. When tocopherol was depleted from either the normal or high cholesterol diets, the following changes occurred in the arterial wall: (1) increase in thiobarbituric acid reactive substances; (2) decrease in lysosomal acid lipase and acid cholesteryl esterase; (3) decrease in the microsomal enzymes, acyl CoA synthetase, triglyceride synthesizing activity, cholesteryl ester synthesizing activity, neutral lipase and neutral cholesteryl esterase; and (4) increase in microsomal CPT. The results of these studies suggest that dietary tocopherol plays an important role in both lipid synthesis and degradation in the arterial wall, and the results may account for the accumulation of lipids and lipoperoxides in atherosclerotic lesions. PMID- 6254479 TI - Endonuclease fingerprinting of plasmids mediating gentamicin resistance in an outbreak of hospital infections. AB - Three plasmids which each determined the same extensive antibiotic resistance phenotype, including resistance to gentamicin, and which had been recovered from organisms involved in an outbreak of gentamicin-resistant infections in Melbourne hospitals in 1975--1976, were analysed by fingerprinting with the restriction endonucleases Eco RI, Hind III and Pst I, In each case the fingerprints for all three plasmids were identical, despite the fact that each plasmid originated in a different host species at different hospitals. This observation confirms our earlier hypothesis (Davey and Pittard, 1977) that the plasmids mediating gentamicin resistance in the outbreak were the closely related descendants of one ancestral (IncL) plasmid. PMID- 6254480 TI - The natural prevalence of antibodies to infectious bursal disease in Australian poultry flocks. PMID- 6254481 TI - Cataracts and depressed galactose-1-phosphate uridyl transferase activity in a cus cus (Phalanger maculatus). PMID- 6254482 TI - Severe rhinotracheitis and pneumonia of feedlot cattle due to bovine herpes virus type 1 infection. PMID- 6254483 TI - Relationships of canine panleucopaenia (enteritis) and myocarditis paroviruses to feline panleucopaenia virus. PMID- 6254484 TI - The isolation of Salmonella from jejunal and caecal lymph nodes of slaughtered animals. AB - One jejunal and one caecal lymph node were sampled from each of 50 cows, 40 yearling cattle, 25 sheep, 20 lambs and 45 pigs after slaughter. Salmonella, Clostridium perfringens and Staphylococcus aureus, all organisms which cause food poisoning in man, were sought by direct plating methods. The samples were also enriched and cultured for Salmonella. Organisms were cultured from 208 (58%) of the 360 lymph nodes; aerobic plate counts yielded up to 25,000 organisms per gram of tissue, although from most infected samples less than 1000 organisms per gram were cultured. Salmonella was isolated directly from 5% of samples, with counts up to 1,500 per gram. After enrichment Salmonella was isolated from nodes taken from 15 cows, 2 yearling cattle, one sheep and 8 pigs. Cl. perfringens was isolated from the caecal nodes of 2 yearling cattle and 2 pigs; S. aureus was not isolated from any sample. It was concluded that mesenteric lymph nodes may be a significant reservoir of Salmonella for transfer to meat and meat products. PMID- 6254485 TI - Role of Coccidia in the occurrence of necrotic enteritis of chickens. AB - Clostridium perfringens type A, Eimeria acervulina, and Eimeria necatrix were used to produce necrotic enteritis in chickens. The disease was produced in all groups of birds that received feed contaminated with C. perfringens. Mortality due to necrotic enteritis was highest (53%) in birds infected with E. acervulina before infection with clostridia. There was a significant difference in mortality rates between birds infected with E. acervulina and birds infected with E. necatrix before infection with C. perfringens. Mortality rates also differed significantly between the group infected with E. necatrix and the group that received only feed contaminated with C. perfringens. It was concluded that under field conditions, coccidia can play a significant role in the occurrence of necrotic enteritis when a sufficient number of toxigenic strain of C. perfringens type A is present. The pathological changes induced by clostridia and coccidia are described. PMID- 6254486 TI - Response of mibolerone-treated chickens to infectious bursal disease virus. AB - The response of mibolerone-treated chickens to infectious bursal disease virus (IBDV) was studied. Chickens fed a ration containing mibolerone at 1.5 parts per million (ppm) developed bursal atrophy by 4 weeks of age. No indication was found that mibolerone prevented IBDV infection even after 7 weeks of feeding. Furthermore, only chickens treated with mibolerone died when infected with IBDV at 2 or 3 weeks of age, and treated chickens had more severe clinical signs than did untreated controls when infected at 4-8 weeks of age. Chickens fed mibolerone had lower body weights than unmedicated controls, and apparently had a lower antibody response to IBDV and to bovine serum albumin. PMID- 6254487 TI - Avian infectious bronchitis in specific-pathogen-free chickens: quantitation of serum immunoglobulins by electroimmunoassay. AB - Immunoglobulin (Ig) levels in serums of individual 6-week-old specific-pathogen free (SPF) chickens differed markedly. Quantitation by electroimmunoassay showed that the IgG level was quite low at 6 weeks of age (1.3 +/- 0.67 mg/ml), increased gradually with maturity, and by 16-18 weeks of age was 2.6 +/- 1.5 mg/ml. IgM levels were less variable during the same observation period (6-18 weeks, 2.4 +/- 0.50 to 2.2 +/- 0.86 mg/ml). IgA was high initially and decreased with age (6-18 weeks, 0.74 +/- 0.78 to 0.26 +/- 0.06 mg/ml). Single intratracheal vaccination with a moderate dose of live avian infectious bronchitis virus (IBV) and subsequent challenge-exposure with live virus via the respiratory tract did not markedly affect Ig levels. Birds vaccinated parenterally 2 or 3 times with live or killed IBV vaccines had a marked increase in serum IgG after similar challenge-exposure. IgA and IgM levels in vaccinated SPF birds approximated those in control SPF birds throughout the experimental period. PMID- 6254488 TI - Development and characterization of a Marek's disease transplantable tumor in inbred line 72 chickens homozygous at the major (B) histocompatibility locus. AB - A serially transplantable Marek's disease (MD) tumor, designated MDCT-RP-3, was developed from an MD-virus-induced lymphoma (GA strain) in a pedigreed female chicken of the inbred B-histocompatible (B2/B2), line 72, and is the first MD tumor transplant to be developed in chickens both syngeneic and selected for susceptibility to MD. The MDCT-RP-3 tumor maintained its female karyotype through at least 80 passages in male 72 chickens. High doses of tumor cells caused progressively growing tumors at 5 days postinoculation and death of young 72 chicks in 7-10 days, whereas allogeneic chicks of other lines were less susceptible. Tumors frequently regressed when doses of tumor cells were low or older chickens were used. MD virus was rescued from MDCT-RP-3 cells in cell culture, and chickens surviving the early transplant response sometimes developed MD lymphomas. The tumor cells expressed MD-tumor-associated surface antigen (MATSA) and T-cell surface antigens. A serum raised in rabbits against MDCT-RP-3 cells and absorbed with normal 72 cells appeared to be reactive against MATSA on all MD tumor cells tested and is probably monospecific. Sera raised against MDCT RP-3 in chickens also contained MATSA antibodies reactive against heterologous but not homologous MD tumor cells. Protection against transplantation of MDCT-RP 3 cells was not afforded by immunization with turkey herpesvirus vaccine. Some unvaccinated chickens that regressed MDCT-RP-3 transplant appeared to be partially immune to later development of MD lymphomas. PMID- 6254489 TI - An indirect enzyme-linked immunosorbent assay (ELISA) for measuring antibodies in chickens infected with infectious bursal disease virus. AB - An immuno-enzyme assay for measuring infectious bursal disease antibodies in chickens is described. The test is performed rapidly after coating plates overnight with partially purified antigen prepared in cell culture. Coated plates can be stored for at last 4 months. The chromatographically purified rabbit anti chicken immunoglobulin-G, conjugated to horseradish peroxidase, was used optimally at a dilution of 1:3,000. It could be stored for at least 10 months without a reduction in titer. The test is safe, highly reproducible, specific, and sensitive. Results can be read visually or by spectrophotometry. Antibodies could be detected as early as 4 days postinfection. Serum titers rose rapidly to high levels, ranging from 1:1,600 to 1:25,600 by one week postinfection. High titers persisted for up to one year. The results of this assay compare favorably with results obtained with the agar-gel precipitin and virus-neutralization tests. PMID- 6254490 TI - Field studies with convalescent serum and infectious bursal disease vaccine to control turkey coryza. AB - Convalescent serum given to 1-day-old poults delayed clinical signs of turkey coryza by several days and reduced mortality on infected farms. Turkey breeders immunized with cell-culture-adapted infectious bursal disease virus (IBDV) or turkey infectious bursal disease virus (TIBDV) had a marked increase in virus neutralization (VN) antibody titers. The VN antibody titer was significantly higher in progeny poults than in poults from unimmunized breeders. Clinical turkey coryza and mortality was considerably less in poults from IBD- or TIBD vaccinated breeders than in control poults. They also responded more favorably to hemorrhagic enteritis and fowl cholera vaccination. PMID- 6254491 TI - An enzyme-linked immunosorbent assay for detection of antibodies to avian adenovirus and avian adenovirus-associated virus in chickens. AB - An enzyme-linked immunosorbent assay system (ELISA) was adapted for the detection of antibodies to avian adenovirus (AV) and avian adenovirus-associated virus (A AV). Both before and after exposure, sera from chickens undergoing natural and experimental infections were assayed by ELISA, virus neutralization (VN), and immunodiffusion (ID) for antibody to both CELO virus and A-AV. The ELISA system was found to be comparable to VN for determining antibody concentrations to CELO virus and A-AV. In many cases, ELISA was found to be more sensitive than ID. PMID- 6254492 TI - Infectious bursal disease virus: further characterization with evidence for a single-stranded RNA virus. AB - Infectious bursal disease virus (IBDV) that had been adapted to grow and was then cloned in chick embryo fibroblast (CEF) cell culture was examined for its physicochemical properties, the cellular site of virus replication, and the nature of its viral RNA. The IBDV was an RNA virus, acid-stable, absolutely resistant to chloroform, and moderately thermolabile. It appeared to replicate only in the cytoplasm, as shown by virus-specific antigens restricted to the cytoplasm of infected cells. The viral RNA was composed of single-stranded RNA, as evidenced by flame-red fluorescence on acridine-orange staining and an absence of specific fluorescence in infected cells on immunofluorescent staining with antiserum specific for double-stranded RNA. The IBDV virion had a hexagonal outline with an average diameter of 62 nm and possessed a single layer of capsid composed of hollow capsomeres without envelope. The buoyant density as determined in a continuous sucrose gradient was 1.178 g/cm3. The IBDV was found to possess morphologial and physicochemical properties different from those of any established RNA virus group. PMID- 6254493 TI - Infectious bronchitis agar-gel precipitin test--use of infected allantoic fluid as antigen. AB - The use of infected allantoic fluid (AF) as precipitating infectious bronchitis (IB) antigen was investigated. The results show that unconcentrated AF harvested at the right time can be a very satisfactory precipitating IB antigen. With the majority of the virus strains used, unconcentrated AF, harvested 68 hours postinoculation (PI), showed more precipitating activity than that harvested at 20 or 120 hours PI. If further antigen concentration is required, dialysis with polyethyleneglycol MW 20,000, freeze-drying, and precipitation with polyethyleneglycol 6,000 are satisfactory methods of concentration. PMID- 6254494 TI - Shedding of lymphoid leukosis virus in chickens following contact exposure and vaccination. AB - Chickens contact-exposed to lymphoid leukosis virus at various ages up to 32 weeks responded with relatively high rates of infection as determined by the presence of neutralizing antibody. Virus shedding as determined by cloacal swab and albumen testing occurred in 7 of 8 groups of such chickens, but the incidence was 10% or less and sporadic. Vaccination of chickens immediately before exposure with a low pathogenicity virus of subgroup A at 8 weeks of age did not eliminate subsequent shedding. PMID- 6254495 TI - Field experiments with viral arthritis/tenosynovitis vaccination of breeder chickens. AB - Vaccination of three commercial broiler-breeder flocks at 15 weeks old with viral arthritis/tenosynovitis via the drinking water resulted in serologic conversion of two flocks to agar-gel-precipitin (AGP)-positive, while the third flock was still AGP-negative at 24 weeks, but was AGP-positive at 30 weeks old, presumably as a result of natural exposure. Progeny from the two successfully vaccinated breeder flocks remained free of clinical viral arthritis/tenosynovitis and had average condemnation rates of 0.99%. In contrast, six hatches of progeny from the third breeder flock experienced clinical viral arthritis/tenosynovitis and average condemnation rates of 3.64%. PMID- 6254496 TI - Adult Coturnix quail bronchitis. AB - Quail bronchitis was confirmed by recovery of fowl adenovirus serotype 1 from 2 flocks of adult birds (Coturnix coturnix japonica) that were reared commercially for their eggs in the Republic of Singapore. Both flocks were reported to have a fall in egg numbers of 10-15%. The main clinical signs were respiratory distress and soft-shelled and white eggs lacking shell pigmentation. PMID- 6254497 TI - Serologic detection of adenovirus infections in specific-pathogen-free chickens. AB - A specific-pathogen-free flock of White Leghorns, which were housed conventionally and were previously serologically negative for all common poultry pathogens including avian adenoviruses, incurred an outbreak of adenovirus that was detected at about 39 weeks of age. The infection was detected serologically through the agar-gel precipitin test (AGPT) and also by a microneutralization test (MNT) adapted for 11 serotypes of avian adenovirus. The MNT detected specific antibodies to serotype-3 avian adenovirus (IBHV-Tipton) but no other serotype. While AGPT-positive sera drawn from the flock gradually declined from 54% to 17%, neutralizing-antibody levels rose sharply at 46 weeks of age to a peak that was maintained over the remaining 18 weeks of the flock's production. PMID- 6254498 TI - Persistence of genomes of both herpesvirus of turkeys and Marek's disease virus in a chicken T-lymphoblastoid cell line. AB - A cell line tentatively designated as MDCC-BO1(T), was established from spleen cells of an apparently healthy chicken inoculated with herpesvirus of turkey (HVT). BO1(T) cells were T lymphoblastoid cells and the more than 95% of them had Marek's disease (MD) tumor-associated surface antigen (MATSA). However, no viral internal antigens or membrane antigens could be demonstrated in them by immunofluorescence tests using chicken anti-HVT and -MD virus (MDV) sera. The virus could be rescued from BO1(T) cells by co-cultivation with chick embryo fibroblasts (CEF). The DNA of the rescued virus was characterized as HVT DNA by its sedimentation profile in a neutral glycerol gradient and its endonuclease Hind III cleavage-pattern. Ultrastructural studies on CEF infected with the rescued virus revealed the presence of HVT-like virions. However, DNA-DNA reassociation kinetics showed that the BO1(T) cells contained a few copies of NVT and also MDV genomes. PMID- 6254499 TI - Immune response of guinea pigs to varicella vaccine strain (OKA) and wild strains. AB - An immune response (neutralizing and complement fixing antibodies) was detected in guinea pigs to varicella vaccine strain (Oka), but not to 2 wild strains. The possible use of guinea pigs and the vaccine strain (Oka) as a model system is discussed. PMID- 6254500 TI - The age distribution of neutralizing antibodies against varicella-zoster virus in healthy individuals. AB - A seroepidemiological survey of varicella was made in the Nagoya area by the neutralization (NT) test. Of 1,473 recorded cases of varicella, 81.4% were under 6 years old and 9.6% were under one year old; of the 168 recorded cases under one year old, about 30% were under 5 months old. Examination of 11 pairs of mother and cord sera and 13 pairs of mother and infant sera showed that transfer of NT antibody was in general good, even in babies that were small for their age or smnall at birth after 28 weeks gestation. The transferred maternal antibody decreased rapidly, becoming undetectable in babies of 4 months old. Then with increase in age the percentgage of seropositive children gradually increased, being 53.3% at 4 to 5 years old, and 100% in those of over 9 years old, with a temporary decrease in young adults in their twenties. PMID- 6254501 TI - A nuclear phosphatase that specifically hydrolyzes pyridoxal 5'-phosphate in mouse liver. PMID- 6254502 TI - The biosynthesis of ubiquitin by parathyroid gland. PMID- 6254503 TI - Stimulatory modulator-requiring cyclic nucleotide-independent protein kinase: partial purification from fetal calf hearts and comparison with various protein kinases. PMID- 6254504 TI - Calcitonin receptors in a cloned human breast cancer cell line (MCF 7). PMID- 6254505 TI - Phosphorylation of calf thymus H1 histone by calcium-activated, phospholipid dependent protein kinase. PMID- 6254506 TI - Identification of the C(6)-S-conjugate of leukotriene A with cysteine as a naturally occurring slow reacting substance of anaphylaxis (SRS-A). Importance of the 11-cis-geometry for biological activity. PMID- 6254507 TI - On the nature of the oxidation-reduction properties of nitrite reductase from Desulfovibrio desulfuricans. PMID- 6254508 TI - Identification of ubiquinone binding proteins in ubiquinol-cytochrome c reductase by arylazido ubiquinone derivative. PMID- 6254509 TI - Detection of oxovanadium (IV) and characterization of its ligand environment in subcellular fractions of the liver of rats treated with pentavalent vanadium(V). PMID- 6254510 TI - Novobiocin and nalidixic acid target proteins in yeast. PMID- 6254511 TI - Interactions of ouabain and vanadate with (Na+,K+)ATPase and isolated cardiac muscle. PMID- 6254512 TI - The occurrence of phosphatidyl choline exchange protein in leaves. PMID- 6254513 TI - Up regulation of corticotrophin receptors by ACTH1-24 in normal and hypophysectomized rabbits. PMID- 6254514 TI - Differential effects of guanine nucleotides on the first step of VIP and glucagon action in membranes from liver cells. PMID- 6254515 TI - Dibutyryl cGMP: inhibitor of the effect of cholecystokinin and gastrin on the guinea pig gallbladder in vitro. PMID- 6254516 TI - Coenzyme A: fatty acid synthetase apoenzyme 4'-phosphopantetheine transferase in yeast. PMID- 6254517 TI - Esterase activity of rabbit pulmonary angiotensin converting enzyme. PMID- 6254518 TI - Mycoplasma pneumoniae: a prokaryote which consumes oxygen and generates superoxide but which lacks superoxide dismutase. PMID- 6254519 TI - Cyclic nucleotide metabolism and reactive oxygen production by macrophages. PMID- 6254520 TI - Identification of an anion channel protein from electric organ of Narke japonica. PMID- 6254521 TI - Conformation of acetylaminofluorene and aminofluorene modified guanosine and guanosine derivatives. PMID- 6254523 TI - Sulfhydryl groups regulate thyroid hormone binding at nuclear receptor sites: further evidence for a separate binding site for reverse T3. PMID- 6254522 TI - Interaction of the dibutylchloromethyltin chloride binding site with the carbodiimide binding site in mitochondria. PMID- 6254524 TI - Coordinate increases in the enzyme activities responsible for phosphatidylglycerol synthesis and CTP:cholinephosphate cytidylyltransferase activity in developing rat lung. PMID- 6254525 TI - Phosphorylation of 1,N6-etheno-ADP in flash groups and the concomitant decay kinetics of the absorption change at 515 nm. PMID- 6254526 TI - Analysis of the reducible components of the muscle protein, connectin: absence of lysine-derived cross-links. PMID- 6254527 TI - Vanadate inhibits 2,3-bisphosphoglycerate dependent phosphoglycerate mutases but does not affect the 2,3-bisphosphoglycerate independent phosphoglycerate mutases. PMID- 6254528 TI - Enzymic synthesis of 5-acetamido-9-azido-3,5,9-trideoxy-D-glycero-D-galacto-2 nonulosonic acid, a 9-azido-9-deoxy derivative of N-acetylneuraminic acid. PMID- 6254529 TI - Erythrosine B (red dye No. 3) mediated oxidation-reduction in brain membranes. PMID- 6254530 TI - Bromodeoxyuridine substitution in mammalian DNA can both stimulate and inhibit restriction cleavage. PMID- 6254531 TI - Transposon (Tn5)-mediated suppressive integration of ColE1 derivatives into the chromosome of Escherichia coli K12 (dnaA). PMID- 6254532 TI - Iron transfer from transferrin to ferritin mediated by pyrophosphate. PMID- 6254533 TI - Solubilization of 20S acetylcholinesterase fro chick retina. PMID- 6254534 TI - Isolation of ACTH1-39,ACTH1-38 and CLIP from the calf anterior pituitary. PMID- 6254535 TI - Isolation and properties of oxidized alpha-1-proteinase inhibitor from human rheumatoid synovial fluid. PMID- 6254536 TI - 5-Methylnicotinamide-resistant variant of mouse lymphoma L1210 cells. PMID- 6254537 TI - Secretagogue-induced transport of H+ and K+ by in vitro amphibian gastric mucosa. PMID- 6254538 TI - Effects of phospholipids on the binding of [3H]dihydroalprenolol to the beta adrenergic receptor of rabbit heart membranes. PMID- 6254539 TI - Effects of chronic dietary lithium on activity and regulation of (Na+,K+) adenosine triphosphatase in rat brain. PMID- 6254540 TI - The 5'-monophosphates of 5-propyl- and 5-ethyl-2'-deoxyuridine do not inhibit the replication of deoxythymidine kinase deficient (TK-) mutants of herpes simplex virus. PMID- 6254541 TI - Effects of 2'-deoxycoformycin infusion on mouse phosphoribosyl pyrophosphate synthetase. PMID- 6254542 TI - The effects of hormones on liver fructose bisphosphatase concentration and activity: application of a new specific radioimmunoassay. PMID- 6254543 TI - Effect of chronic treatment with antidepressants on beta-adrenergic receptor binding in guinea pig brain. PMID- 6254544 TI - [Effects of polymyxin B and E (colistin) on blood coagulation, thrombocyte function, and fibrin structure (author's transl)]. AB - Polymyxins are known to form complexes with endotoxins and phospholipids. Therefore patients with septicaemia were treated in some studies with polymyxin. We investigated the effect of polymyxin B and E (colistin) on some blood coagulation parameters, spreading of platelets and fibrin polymerisation. With increased concentrations of polymyxin (1, 5, 10, 20, 100 mg%) we found a significant prolongation of prothrombin, partial thromboplastin and TEG reaction times. Spreading of platelets was also reduced. There was, however, no effect on fibrin polymerisation. The coagulation inhibitory effects of polymyxins could be reduced by adding phospholipids as procoagulant. These results indicate: 1. There are anticoagulant effects of polymyxins even in therapeutic doses and therefore it should not be applied in cases of haemorrhagic diathesis or renal insufficiency. 2. In septicaemia the disseminated intravascular coagulation can be prevented because due to consumption of polymyxin, endotoxinaemia persists. PMID- 6254545 TI - A review of the effects of fenbufen and a metabolite, biphenylacetic acid, on platelet biochemistry and function. AB - gamma-Oxo(1,1'-biphenyl)-4-butanoic acid (fenbufen) and biphenylacetic acid have effects on platelets similar to other non-steroidal antiinflammatory agents. In vitro biphenylacetic acid (BPAA), a metabolite of fenbufen, is more potent than fenbufen and in vivo metabolism of fenbufen to BPAA is probably required for activity. The arachidonate-thromboxane system appears to play a critical role in explaining a major part of the mechanism of action of these agents on platelets and other systems. Fenbufen, however, also inhibits collagen-induced platelet aggregation without requiring metabolic conversion to BPAA. The mechanism for this inhibition appears to be independent of the arachidonate-thromboxane system, as well as unrelated to serotonin release or inhibition of phosphodiesterase activity. The effects of fenbufen and BPAA on platelet biochemistry and function suggest their utility as clinical anti-thrombotic agents. This is further supported by the absence of any thrombocytopenia or bleeding tendency in animals and man. PMID- 6254546 TI - Mechanism of cardiovascular action of trapidil. AB - In anaesthetized, open-chest dogs N,N-diethyl-5-methyl[1,2,4]triazolo[1,5 alpha]pyrimidine-7-amine (trapidil) in doses of 0.3--3 mg/kg i.v. produced increases in coronary sinus outflow and heart rate and decreases in systemic blood pressure and coronary resistance in a dose-dependent manner. Trapidil produced an increase in myocardial oxygen consumption but virtually no change in coronary arteriovenous oxygen difference. At 1.8 mg/kg i.v. of the drug coronary resistance fell to half of the pre-drug value and coronary sinus outflow almost doubled, and so did myocardial oxygen consumption. In isolated, blood-perfused dog heart preparations, trapidil produced coronary vasodilator and positive inotropic and chronotropic effects. Theophylline produced similar effects. Trapidil was a more positive inotropic than positive chronotropic agent, and so was theophylline but to a lesser degree than trapidil. In producing vasodilator and positive inotropic effects trapidil was about 3 times more effective than theophylline. Trapidil and theophylline inhibited the cyclic AMP phosphodiesterase (PDE) activity in crude extracts prepared from the dog ventricular muscle. In this respect trapidil was nearly 3 times more potent than theophylline. It is suggested that PDE inhibition would be a fundamental mechanism of action of trapidil. PMID- 6254547 TI - Effects of trapidil on electrical activities of canine ventricular muscle. AB - The effects of N,N-diethyl-5-methyl[1,2,4]triazolo[1,5-alpha]pyrimidine-7-amine (trapidil) on the electrical activities of canine right ventricular muscle were studied using standard microelectrode techniques. Trapidil (10(-4) and 10(-3) mol/l) increased the plateau amplitude and shortened the duration of the action potential without changing the resting membrane potential and the maximum rate of rise of the action potential. Trapidil (10(-3) mol/l) restored regenerative action potentials (the slow response) in the ventricular muscle depolarized by elevation of extracellular K+ concentrations to 30 mmol/l. The slow response induced by trapidil was not affected by pindolol (10(-7) mol/l) which abolished that elicited by isoprenaline (10(-6) mol/l). These results indicate that the action of trapidil on the cardiac cell membrane is to increase the slow inward current during the action potential independently of stimulation of beta adrenoceptors. Taken together with the results obtained by previous investigations the present results suggest that the increase in slow inward current during the action potential would be responsible for the positive inotropic effect of trapidil and would probably be related to its inhibitory action on cyclic AMP phosphodiesterase. PMID- 6254548 TI - [Pathogenesis and pathophysiology of myasthenia gravis--electrophysiological, ultrastructural and immunological aspects of neuromuscular junctions (author's transl)]. PMID- 6254549 TI - Neuromuscular pharmacology. PMID- 6254550 TI - Beta-adrenoceptors in human lung, bronchus and lymphocytes. PMID- 6254551 TI - Peripheral analgesia: mechanism of the analgesic action of aspirin-like drugs and opiate-antagonists. AB - 1 Prostaglandins released by tissue injury sensitize nociceptors and produce hyperalgesia. 2 Aspirin-like drugs inhibit prostaglandins I2 and E2, synthesis, which explains their anti-algic effect. 3 The anti-algic effect of aspirin-like drugs in carrageenin-induced rat paw inflammation may involve a central component. 4 Prostaglandin E2-induced hyperalgesia, once established, is not relieved by systemically administered drugs. 5 Prostaglandin-induced hyperalgesia is possibly a cyclic adenosine, 3',5'-monophosphate C2+ dependent process. 6 Morphine, enkephalins, opiate antagonists and cyclic guanosine 3',5' monophosphate have a peripheral analgesic effect in the prostaglandin hyperalgesia test. 7 Morphine may produce peripheral analgesia by inhibiting adenylatecyclase activity at the nociceptors. PMID- 6254552 TI - Human breast-cancer xenografts in immune-suppressed mice. AB - Eight serially transplantable human breast-cancer xenograft lines have been established in immune-suppressed mice. Specimens from 102 primary and secondary lesions obtained at surgery from 80 patients were implanted into mice immune suppressed by thymectomy and whole-body irradiation. A number of variations of implantation site, transplantation technique, method of immune suppression and hormonal manipulation of the host were tried in an attempt to increase the take rate, but without success. The 8 lines established have been serially transplanted into further immune-suppressed mice for at least 2 passages, and appear to maintain characteristic human histopathology, chromosome number and tumour-marker production. None of the tumours show hormone sensitivity. The poor take rate may be a reflection of the biological nature of breast cancer rather than a failure of the immune-deprivation technique, as many other human tumours grow well as xenografts in this system. PMID- 6254553 TI - Chemotherapy of human breast-carcinoma xenografts. AB - Five lines of human breast-carcinoma xenografts have been tested for sensitivity to cyclophosphamide, methotrexate, 5-fluorouracil, adriamycin, vincristine and melphalan, alone and in combination, using tumour growth delay as an end-point. The xenograft lines were established and passaged in mice immune-suppressed by thymectomy and whole-body irradiation. There was a considerable range of sensitivity of the different lines to the agents studied, and within this variation there was evidence that the most effective single agent or combination differed for each tumour. Combination chemotherapy was more effective than single agents in 3 of the lines, but melphalan was more effective than either combination in the other 2. It is suggested that a panel of human breast tumours grown in immune-suppressed mice may prove useful in testing new cytotoxic agents for activity against breast cancer before their use in clinical trials, and that more effective combinations of existing drugs might be designed with the aid of this system. PMID- 6254554 TI - Antigenic modulation of mammary tumour virus envelope antigen or GR thymic lymphoma cells in relation to expressions of H-2, TL cell-surface antigens and THY1. AB - The MLr antigen, a mammary tumour virus-induced antigen on the surface of GR thymic lymphoma cells (GRSL) can be modulated from the cell surface upon incubation with specific antiserum for 1-2 h at 37 degrees C, followed by washing the cells. In contrast, a number of other cell-surface antigens on these GRSL cells cannot be modulated under similar conditions. These antigens include histocompatibility antigens of the H-2 complex (H-2.8 of the K-end and H-2dx(D) of the H-2dx haplotype) and two thymic markers, TL1.2 and Thy1.2. Antigenic modulation of MLr as tested by trypan-blue exclusion and by chromium51 release does not lead to a measurable change in the expression of H-2K, H-2D, TL and Thy1.2 antigens. These results could be confirmed by absorption analysis. The latter analysis showed that the number of antigenic sites per cell are about the same for MLr and the two H-2 antigens, while TL antigens are scarcer and Thy1.2 antigens are more abundant. The procedure of antigenic modulation showed that the MLr antigen resides on MTVgp52, the major protein of the envelope. There was no evidence of internal proteins, such as MTVp27, on the surface of GRSL cells. PMID- 6254556 TI - Endocervical adenocarcinoma and vulval Paget's disease: a significant association. AB - Extra-mammary Paget's disease is an uncommon entity. It has been associated with a underlying sweat gland carcinoma. This paper presents a patient with metastatic endocervical carcinoma and vulval Paget's disease. We believe that the Paget's disease developed as a direct consequence of the cervical tumour. In patients with extra-mammary Paget's disease with no sweat gland carcinoma a careful search to exclude other primary malignant tumours is advised. PMID- 6254555 TI - Treatment of tumours with the combination of WR-2721 and cis dichlorodiammineplatinum (II) or cyclophosphamide. AB - The ability of WR-2721 [S-2(3-aminopropylamino)ethyl-phosporothioic acid] to selectively protect the host against the toxic effects of multiple doses of cis dichlorodiammineplatinum [cis-Pt] or cyclophosphamide [CY] has been studied in mice and rats bearing 3 different tumours. Selective protection against cis-Pt induced nephrotoxicity has been demonstrated under all conditions studied, with the extent of protection being inversely related to the size of the cis-Pt dose. For example, pre-treatment with 200 mg/kg of WR-2721 30 min before each weekly dose of 2 mg/kg of cis-Pt allows the administration of this cytotoxic agent for 3 times longer before nephrotoxic injury. In none of these studies was there tumour protection. The same pattern was observed with CY, but quantitation of the extent of marrow protection was not possible for the multiple treatment studies, due to the longer latent period between induced and observed death with this drug. We conclude, therefore, that for both of these drugs, selective protection of the kidney and marrow is not only maintained under conditions of multiple treatment, but actually enhanced due to the need for smaller doses of cytotoxic agents in these protocols. PMID- 6254557 TI - Sinus histiocytosis with massive lymphadenopathy: virological, immunological and morphological studies. AB - The histiocytes from a patient with sinus histiocytosis were tested for the presence of Epstein-Barr viral nuclear antigen (EBNA) before and after in vitro growth. On both occasions the histiocytes as well as the lymphocytes were EBNA negative. Likewise the profile of EBV viral capsid antibody (VCA) suggests that this virus is unlikely to be directly involved in the development of the disease. The maintenance of an unusually high level of antibodies to EBV and measles, both viruses which produce persistent infections, indicates that the humoral immune response is active. That a normal humoral response occurred in response to mumps virus during the same period suggests that a deficiency in the cell mediated immune response to the persistent viruses might be the reason for the abnormally high antibody levels. The fresh as well as the cultured histiocytes had only Fc receptors. The affected lymph node lymphocytes developed unusual large inclusion bodies following in vitro culture. PMID- 6254558 TI - Ultrastructural cytochemistry of leukaemic cells: characterization of the early small granules of monoblasts. AB - An ultrastructural study of blast cells showing either monocytic or granulocytic differentiation was carried out with the acid phosphatase (AP) and myeloperoxidase (MPO) reactions. Eight cases of acute myeloid leukaemia (AML) and three of chronic granulocytic leukaemia in blast crisis were studied. A hitherto unrecognized small lysosomal granule characterized by AP activity and lack of MPO was present in the majority of cells of all six monoblastic leukaemias. These granules ranged from 0.05 to 0.2 micron in size and were distributed throughout the cytoplasm, frequently at the periphery of the cells. A small proportion of monoblasts showed AP reactivity in the Golgi cisternae. Both AP and MPO were positive in the granules of promonocytes; however, MPO positive granules were predominant in late promonocytes. Larger granules (0.2--0.6 micron) with MPO reactivity were characteristic of myeloblasts. In only two out of four cases did these granules show AP positivity, suggesting that, in contrast to monoblasts, AP activity is a late feature of myeloblastic differentiation. This study shows that ultrastructural cytochemistry may be helpful in the recognition and classification of acute leukaemias by demonstrating the early differentiation features of monocytic and granulocytic precursors. PMID- 6254559 TI - Electron spin resonance in haematological research. PMID- 6254560 TI - Male pseudohermaphroditism with 17 alpha-hydroxylase deficiency. A case report. AB - A case of male pseudohermaphroditism with 17 alpha-hydroxylase deficiency is reported in a 23-year-old woman presenting with primary amenorrhoea and a history of bilateral inguinal hernia repair. She was tall, had hypoplastic external genitalia with a blood pressure of 220/140 mm Hg. Her karyotype was XY. Acute adrenal failure occurred following exploratory laparotomy. After treatment with glucocorticoids and oestrogens, the hormone and electrolyte profiles returned to normal and the blood pressure fell. The biochemical implications of this enzyme deficiency are discussed. PMID- 6254561 TI - Utilization of low quality roughages: effects of urea and protein supplements of differing solubility on digesta flows, intake and growth rate of cattle eating oaten chaff. AB - 1. Expt 1. Five 150 kg steers with ruminal, abomasal and ileal cannulas were given 3000 g oaten chaff daily plus pelleted supplement with no added nitrogen (diet A) of 50 g N/d as urea (diet B), casein (diet C), casein and formaldehyde treated casein (HCHO-casein) (50:50 w/w; diet D) and HCHO-casein (diet E), in a 5 x 5 Latin square design. The basal diet and supplement were fed in eight equal increments at intervals of 3 h. Proportions of dry matter and organic matter digested in the stomach and whole tract were greater for diets B, C, D and E than for diet A. Total volatile fatty acid levels in the rumen and the proportion of acetic acid, were lower, and the proportion of propionic acid higher on diet A than on the other diets. Rumen ammonia levels were lower on diets A, D and E than on diets B and C. N flows at the abomasum, ileum and rectum were lower on diet A than on the other diets; abomasal flows and apparent intestinal absorptions of amino acids were higher on diets D and E than on diets A, B and C. Efficiencies of bacterial protein synthesis were 15, 15, 14, 13 and 12 g bacterial N/kg OM truly digested in the stomach on diets A, B, C, D and E respectively. 2. Expt 2. Forty 300 kg steers were fed oaten chaff ad lib. plus twice the amount of the same pelleted supplements as in Expt 1. Intake of oaten chaff was 23% higher with N supplements (diets B, C, D and E) than without (diet A). Live-weight gains were 356, 798, 843, 842 and 805 g/d on diets A, B, C, D and E respectively. 3. It was concluded that efficiency of bacterial protein synthesis was not limited by the supply of peptides and amino acids in the rumen, and that increases in amino acid availability in the intestines from feeding HCHO-casein did not increase food intake or live-weight gain. PMID- 6254562 TI - Cytochrome c specifically induces non-bilayer structures in cardiolipin containing model membranes. AB - (1) The effect of cytochrome c addition on the phospholipid structure of liposomes composed of cardiolipin, phosphatidylserine, phosphatidylglycerol, phosphatidylcholine or phosphatidylethanolamine in a pure form or in mixtures was investigated by 31P-NMR and freeze-fracture techniques. (2) Cytochrome c specifically induces the hexagonal Hii phase and possibly an inverted micellar structure of part of the phospholipids in cardiolipin-containing model membranes. (3) These results are compared with the effect of Ca2+ on cardiolipin and are discussed in relation to the structure and function of the inner mitochondrial membrane. PMID- 6254563 TI - Incorporation of hydrophilic protein modified with hydrophobic agent into liposome membrane. AB - The hydrophilic protein-enzyme, alpha-chymotrypsin, can be bound to the liposomal membrane after the preliminary increase in hydrophobicity induced by acylation of protein amino groups with palmitic chloroanhydride. The efficacy of binding depends on the degree of modification. The bound enzyme almost completely preserves its catalytic properties and the ability to interact with a high molecular weight inhibitor. Binding can be performed during both the process of liposome formation and the incubation of a modified enzyme with preformed liposomes. According to ESR and fluorescence spectroscopy, the hydrophobic tail of the modified enzyme is incorporated into the membrane and the protein globule is located on the surface of the membrane. Protein incorportation causes an increase in the amorphous nature of the membrane, and the bound protein is not as mobile as the free protein. The approach discussed can be useful in binding soluble hydrophilic proteins to artificial membranes. PMID- 6254564 TI - Pressure-induced changes in the molecular organization of a lipid-peptide complex: polymyxin binding to phosphatidic acid membranes. AB - The effect of 100 atm pressure on the organization of the lipid-peptide complex formed between polymyxin and dipalmitoyl phosphatidic acid has been investigated. Phase transition curves were obtained by electron paramagnetic resonance by measuring the partition coefficient of the spin label, 2, 2, 5, 5 tetramethylpiperidine-N-oxyl. The three-step phase transition curve previously obtained with fluorescence polarization measurements was confirmed, demonstrating three distinct phosphatidic acid domains in the bilayer. Pressure increases binding of polymyxin to phosphatidic acid bilayers and alters the proportions of the two domains that differ in the mode of binding between phosphatidic acid and polymyxin. The binding curves of polymyxin to phosphatidic acid bilayers wre determined and it was shown that application of pressure reduces the cooperativity of the binding curve. PMID- 6254565 TI - Transition temperatures of the electrical activity of ion channels in the nerve membrane. AB - The temperature dependence of some of the electrical characteristics of neuronal membranes from Aplysia giant neurons and crustacean and cuttlefish giant axons has been analyzed. Arrhenius plots for the maximum rate of depolarization of (V+max) or repolarization (V-max) of the action potential, for the resting membrane conductance, and for the speed of propagation of the action potential, exhibited clear breaks at characteristic temperatures between 17 and 20 degrees C. Lobster giant axons and frog nodes of Ranvier were voltage-clamped at different temperatures between 5 and 30 degrees C. Arrhenius plots for relaxation times related to the opening and closing processes affecting the Na+ and K+ channels were linear. No 'transition' temperature was detected. However, clear cut changes in (Formula: see text) Na+ and K+ currents, were consistantly observed around 18 degrees C. Values for (Formula: see text) plateaued above 18 degrees C, then decreased gradually as a function of reduced temperature. Variations in temperature between 1 and 30 degrees C did not alter the binding properties of [3H]tetrodotoxin to a purified crab axonal membrane. Pharmacological properties of the Na+ channel are sensitive to temperature. The temperature-dependent effect of veratridine has been studied and indicates a change in properties of the Na+ channel below 20 degrees C. These results support the possibility that the fluidity of membrane lipids in the ionic channel microenvironment may influence the degree to which the channel can open. PMID- 6254566 TI - The effect of hemin, adenosine 3',5'-monophosphate and phosphorylated sugars on Met-tRNAfMet deacylase activity in rabbit reticulocyte lysates. AB - The effect of hemin, phosphorylated sugars, adenosine 3',5'-monophosphate (cyclic AMP) and a number of purines on a specific initiator tRNA deacylase activity in rabbit reticulocytes has been investigated. In the concentration range established to be optimal for maximal stimulation of translation (5.5-30.0 microM), hemin produces a 20-82% inhibition of Met-tRNAfMet deacylation. In contrast, all phosphorylated sugars tested, with the exception of fructose 1,6 diphosphate, are without effect. High concentrations of cyclic AMP (2-4 mM) also significantly inhibit the deacylase activity. The role of hemin and Met-tRNAfMet deacylase in the control of peptide initiation are discussed. PMID- 6254567 TI - Stimulatory factor for tRNA aminoacylation: possible product of modifier genes in Drosophila melanogaster. AB - A factor which stimulates the aminoacylation of heterologous and homologous tRNAs for lysine and leucine, as well as a mixture of amino acids, has been isolated from cytoplasmic extracts in Drosophila. The stimulatory factor is separated from inorganic pyrophosphatase activity by DEAE-cellulose chromatography and from aminoacyl-tRNA synthetase activity by trichloroacetic acid precipitation. It contains no nucleotidyl transferase activity. It is trypsin-sensitive and heat stable, indicating that it may be a small protein. Attempts to measure the molecular weight, however, indicate heterogeneity in size, ranging from 20,000 to 65,000. The A53g mutant has four times as much factor Ore-R adults at 0-2 days; by 6-8 days the level has declined to less than one and a half times that of Ore R. The heightened aminoacylation activity in the mutant extract is accompanied by increased soluble protein levels. It is known that the stimulation of tRNA aminoacylation in A53g is controlled by modifier genes which enhance the expression of the A53g mutant. The possibility that the stimulation factor is a product of the modifier genes is examined. PMID- 6254568 TI - The use of fluorescence correlations spectroscopy to probe chromatin in the cell nucleus. AB - All systems in thermodynamic equilibrium are subject to spontaneous fluctuations from equilibrium. For very small system, the fluctuations can be made apparent, and can be used to study the behavior of the system without introducing any external perturbations. The mean squared amplitude of these fluctuations contains information about the absolute size of the system. The characteristic time of the fluctuation autocorrelation function contains kinetic information. In the experiments reported here, these concepts are applied to the binding equilibrium between ethidium bromide and DNA, a system where the fluorescence properties of the dye greatly enhance the effect of spontaneous fluctuations in the binding equilibrium. Preliminary experiments employ well-characterized DNA preparations, including calif thymus DNa, SV40 DNA, and calf thymus nucleohistone particles. Additional measurements are described which have been made in small regions of individual nuclei, isolated from green monkey kidney cells, observing as few as 5000 dye molecules. The data indicate that the strength of dye binding increases in nuclei isolated from cells which have been stimulated to enter the cell growth cycle. The viscosity of nuclear material is inferred to be between one and two orders of magnitude greater than that of water, and it decreases as the cells leave the resting state and enter the cell growth cycle. Washing the nuclei also lowers the viscosity. These experiments demonstrate that fluorescence correlation spectroscopy can provide information at the subnuclear level that is otherwise unavailable. PMID- 6254570 TI - Purified proenzyme C1r. Some characteristics of its activation and subsequent proteolytic cleavage. AB - 1. Upon incubation for 1 h at 37 degrees C, proenzymic C1r was activated by a proteolytic cleavage comparable to that observed in vivo; after reduction and alkylation, two fragments of apparent molecular weights 57 000 and 35 000 were evident on sodium dodecyl sulphate (SDS)-polyacrylamide gel electrophoresis. The activation kinetics were slightly sigmoidal and nearly independent of C1r concentration. They were characterized by a marked thermal dependence (activation energy = 45 kcal/mol). The reaction was inhibited by calcium and p-nitrophenyl-p' guanidinobenzoate, but poorly sensitive to di-isopropyl phosphorofluoridate. The dependence of the activation rate on pH was unusual; it decreased progressively in the acid range (pH 4.5-6.5) which coincides with the dissociation of the C1r C1r dimer. Above pH 6.5, the rate increased slightly and showed no clear maximum. These results are consistent with an intramolecular autocatalytic activation mechanism involving the pro-site of each subunit of the C1r-C1r dimer. 2. During a 5 h incubation period at 37 degrees C, C1r underwent two proteolytic cleavages which led to the successive removal of two fragments, alpha (35 000) and beta (7000-11 000) from each subunit, leaving a dimeric molecule of reduced size (Mr = 110 000; s20,w = 6.1 S). The proteolytic process was nearly independent of C1r concentration and characterized by a pH optimum at 8.5-9.0, and a high activation energy (36.8 kcal/mol). Calcium and p-nitrophenyl-p'-guanidinobenzoate, and also di-isopropyl phosphorofluoridate and benzamidine were inhibitors of this reaction. The product, C1r II, retained the original antigenic properties of C1r and a functional active site, but lost the capacity to bind C1s. These results are consistent with an autocatalytic intramolecular proteolysis mediated by the active site of each subunit of the C1r-C1r dimer. PMID- 6254569 TI - Characterization and stability of hydrogenase from Chromatium. AB - The absorption spectrum of the hydrogenase from Chromatium, which contains four iron atoms and four atoms of acid-labile sulfide, in 80% dimethylsulfoxide or hexamethylphosphoramide suggests the presence of a single [4Fe-4S] cluster. The EPR spectra of the oxidized enzyme in air, argon or carbon monoxide are the same with signals centered at g = 2.01. The enzyme reduced by hydrogen is EPR silent. The EPR spectrum is consistent with a [4Fe-4S] cluster. Chromatium hydrogenase and the hydrogenase from Proteus vulgaris show relative stability towards denaturation by sodium dodecyl sulfate (SDS), urea, guanidine and organic solvents. PMID- 6254571 TI - Purification of nucleosidediphosphatase of rat liver by metal-chelate affinity chromatography. AB - A procedure is presented for the purification of nucleosidediphosphatase (nucleosidediphosphate phosphohydrolase, EC 3.6.1.6) of rat liver by affinity chromatography using metal conjugated to epoxy-activated Sepharose 6B. The enzyme is eluted from the conjugate by a solution of L-histidine. The enzyme, when bound to metal-chelate gel, is active in a suspended form, suggesting that the catalytic site is different from the site that binds to the metal-chelate gels. Substrate specificity and Km value of the enzyme obtained are similar to those of the enzyme obtained from the same sources by a conventional procedure, indicating that the metal-chelate affinity chromatography does not bring about any substantial change in the catalytic properties. PMID- 6254572 TI - Superoxide dismutase content and microsomal lipid composition of tumours with different growth rates. AB - The content of cytosolic superoxide dismutase has been determined in Morris hepatomas 3924A (fast-growing) and 44 (slow-growing) and in ascites tumour cells (Novikoff hepatoma and Ehrlich-Lettre). The enzyme is decreased in all the tumours examined. The lowest amounts were found in the tumours with the fastest growth rates. Measurements of the lipid composition and fluidity of microsomal membranes isolated from Morris hepatomas show that also these parameters are changed in relation to the growth rate. The lipid to protein ratio and the degree of fatty acid unsaturation decrease gradually from rat liver to hepatoma 44 and 3924A microsomes. The different lipid composition is reflected also by differences in the physical environment of the bilayer, as indicated by data obtained with spin-labeled fatty acids. It is proposed that the changes in the membrane lipid composition and organization are consequent to the decrease in the protective effect of cytosolic superoxide dismutase against the O2- induced lipid peroxidation. PMID- 6254573 TI - Identification of 4-hydroxynonenal as a cytotoxic product originating from the peroxidation of liver microsomal lipids. AB - During the NADPH-Fe induced peroxidation of liver microsomal lipids, products are formed which show various cytopathological effects including inhibition of microsomal glucose-6-phosphatase. The major cytotoxic substance has been isolated and identified as 4-hydroxy-2,3-trans-nonenal. The structure was ascertained by means of ultraviolet, infrared and mass spectrometry and high-pressure liquid chromatographic analysis. Moreover, 4-hydroxynonenal, prepared by chemical synthesis, was found to reproduce the biological effects brought about by the biogenic aldehyde. Preliminary investigations suggest that as compared to 4 hydroxynonenal very low amounts of other 4-hydroxyalkenals, namely 4 hydroxyoctenal, 4-hydroxydecenal and 4-hydroxyundecenal are also formed by actively peroxidizing liver microsomes. In the absence of NADPH-Fe liver microsomes produced only minute amounts of 4-hydroxyalkenals. The biochemical and biological effects of synthetic 4-hydroxyalkenals have been studied in great detail in the past. The results of these investigations together with the finding that 4-hydroxyalkenals, in particular 4-hydroxynonenal, are formed during NADPH Fe stimulated peroxidation of liver microsomal lipids, may help to elucidate the mechanism by which lipid peroxidation causes deleterious effects on cells and cell constituents. PMID- 6254574 TI - Ontogenetic development of isoproterenol subsensitivity of myocardial adenylate cyclase and beta-adrenergic receptors in spontaneously hypertensive rats. AB - [3H]Dihydroalprenolol binding and adenylate cyclase activity in the myocardial membranes of Kyoto Wistar normotensive rats and spontaneously hypertensive rats were compared at various stages of postnatal development ranging from 2 to 36 weeks. Basal as well as agonist-stimulated myocardial adenylate cyclase activity was consistently decreased in spontaneously hypertensive rats as compared to normotensive rats as early as 2 weeks of age with significant differences (P < 0.05) observed after 6 weeks of age. When results were expressed as percent stimulation over the basal activity, only isoproterenol plus GTP-stimulated enzyme activity was reduced by 25--30% in spontaneously hypertensive rats, suggesting a specific loss of stimulation by isoproterenol in hypertensive animals. The number of [3H]dihydroalprenolol binding sites of KD for dihydroalprenolol binding were comparable between spontaneously hypertensive and normotensive rats at 3, 6 and 12 weeks of age. The competition of isoproterenol with [3H]dihydroalprenolol for the specific binding sites showed that the affinity of isoproterenol binding was decreased 3--4-fold in spontaneously hypertensive compared with normotensive rats. With postnatal development in age, basal as well as agonist-stimulated activities decreased progressively in both spontaneously hypertensive and normotensive rats. Similarly, the number of [3H]dihydroalprenolol binding sites decreased with the development in age, whereas affinity of dihydroalprenolol binding increased up to 12 weeks of age. These results therefore suggest that adenylate cyclase activity and the number of beta-adrenergic receptors in rat heart, decrease with age and that in hypertension, specific decrease in isoproterenol stimulation of cyclase appears at all stages of development. PMID- 6254575 TI - Multiple genetic changes determine ribose utilization by Novikoff hepatoma cell variants. AB - In variants of the Novikoff hepatoma cell line, the ability to use D-ribose as a carbon source appeared to be due to changes in the expression of ribokinase. Examination of ribokinase activity was prompted by the finding that uptake of radiolabeled ribose was linear for 30 min in six variants but became saturated within 2 min in nine other variants. The linear uptake of ribose was due to a high rate of phosphorylation by ribokinase. Variants which showed linear uptake kinetics had ribokinase levels of 6.8 +/- 1.7 nm/min per mg protein as compared to the parental levels of 0.90 +/- 0.25 nm/min per mg protein. The nine variants which showed saturable uptake kinetics had low parenteal levels of ribokinase. However, these variants showed a change in the subcellular location of that activity. The enzyme was predominantly membrane-associated in both parental cells and high ribokinase variants. In contrast, the low ribokinase variants had a cytoplasmic form of the enzyme. A more general membrane change probably occurred in these variants, since they showed an increased sensitivity to the unrelated membrane reactive compounds, phytohemagglutinin and ouabain. PMID- 6254576 TI - Gluconeogenesis in rabbit liver. III. The influences of glucagon, epinephrine, alpha- and beta-adrenergic agents on gluconeogenesis in isolated hepatocytes. AB - 1. Gluconeogenesis from various substrates has been demonstrated in hepatocytes from 48 h fasted rabbits. Maximum rates of gluconeogenesis (expressed as mumol glucose formed/30 min per 10(8) cells) are: D-fructose, 9.86; dihydroxyacetone, 5.28; L-lactate, 5.26; L-lactate/pyruvate, 3.83; pyruvate, 3.32; glycerol, 2.92; L-alanine, 2.24. 2. Gluconeogenesis from L-lactate is enhanced 1.3--1.5-fold over control values by glucagon, L-epinephrine, L-norepinephrine, dibutyryl cyclic AMP, L-phenylephrine and L-isoproterenol. Glucogenesis from both dihydroxyacetone and D-fructose is stimulated 1.7--2.0-fold of control values by glucagon, epinephrine and dibutyryl cyclic AMP. 3. Gluconeogenesis from lactate is enhanced by both alpha- and beta-adrenergic stimulations based on findings with alpha- and beta-agonists and antagonists. 4. Enhancement of gluconeogenesis by epinephrine and norepinephrine is apparently due to both alpha- and beta-adrenergic effects, as either propranolol or phentolamine partially inhibits such enhancement. The consistently more pronounced inhibition produced by propranolol implies that stimulation of glucose formation by catecholamines is more strongly beta adrenergic related. Epinephrine-induced glycogenolysis in rabbit hepatocytes is severely inhibited by propranolol but insensitive to phentolamine, suggesting that glycogen breakdown is solely beta-adrenergic related. These observations contrast with those of others that stimulation of both gluconeogenesis and glycogenolysis by catecholamines while sensitive to both alpha- and beta adrenergic stimulation in rats, at least young rats, is primarily alpha adrenergic mediated, especially in adult rats. PMID- 6254577 TI - Formaldehyde as a pre-treatment for dermal collagen heterografts. AB - The preparation, stability both in vitro and in vivo and resistance to bacterial collagenase of trypsin-purified pig dermal collagen cross-linked with a range of concentrations of formaldehyde in phosphate-buffered saline, was studied using 14C-labelled formaldehyde as a tracer. Washing in phosphate-buffered saline at 37 degrees C produced rapid loss of formaldehyde over 6 weeks before stability was reached. After 19 weeks washing, 12-20% of the initial radioactivity remained, representing 6, 18 and 35 mumol formaldehyde/g of collagen after 21 days reaction with 0.1, 1 and 5% formaldehyde, respectively. Collagen, incorporating stable bound formaldehyde arising from reaction with formaldehyde in concentrations of 0.5% or over, was totally resistant to bacterial collagenase. The stabilizing effect of formaldehyde cross-linking was also demonstrated by implants of fibrous pig dermal collagen in rats. After 8 weeks a significant constant amount of formaldehyde was retained in all implants. There was no net loss of mass over a 24 week period when pre-treated with 1% formaldehyde but some loss when pre treated with 0.1% formaldehyde. PMID- 6254578 TI - Low molecular weight cyclic AMP binding protein isolated from the extract of human tonsillar lymphocytes. AB - A protein fraction of molecular weight 33,000-36,000 accounted for about 40% of the cyclic AMP binding capacity of the cytoplasmic extract of human tonsillar lymphocytes. This cyclic AMP binding fraction (designated as R' protein [10]) proved to be a proteolytic fragment of the regulatory subunit of the cyclic AMP dependent protein kinase. The Scatchard plot of cyclic AMP binding by the isolated R' fraction indicated positive cooperativity. 50% saturation of the cyclic AMP binding sites was achieved at about 4 . 10(-9) M cyclic AMP. An upward concave curve was obtained in the Scatchard plot of cyclic GMP binding by the R' protein. These results strongly suggest that more than one molecule of cyclic nucleotide can be bound by one molecule of the R' protein. The R' protein could not be detected in the physiological salt extract of isolated nuclei in which type I cyclic AMP-dependent protein kinase was the dominating isoenzyme (according to the terminology used by Corbin, S.D., Keely, S.L. and Park, C.R. (1975) J. Biol. Chem. 250, 218-225). The cytoplasm of cells contained a higher amount of type II than type I regulatory subunit. In the cytoplasm the predominant part of RII was present in the dissociated state in all preparations, while when the RII was found in the nucleus it was mainly in the holoenzyme form. The R' protein presumably from the dissociated type II regulatory subunit. PMID- 6254579 TI - Disturbance of kidney aldosterone sensitivity and the mechanism of its development during neurodystrophy. AB - It has been established that neurodystrophy resulting from the sectioning of an animal's left sciatic nerve and treatment of its central stump with formalin leads to a prolonged disturbance of the water- and salt-excreting function of the kidneys. As a rule, this is expressed as oligouria and decreased excretion of sodium in the urine. The indicated changes are due to disturbance of both intra- and extrarenal mechanisms. Intrarenal mechanisms of oligouria basically involve an acute depression in filtration of primary urine, and the hyponatriuresis is due to a decrease in the sodium load of the nephron and to an increase in the tubular reabsorption of sodium. Extrarenal mechanisms implicated in the indicated changes in sodium reabsorption involve an increased concentration of mineralocorticoid hormones of the body. Further studies have shown that the hyponatriuresis which arises during neurodystrophy is related not only to the increased concentration of the above-mentioned hormones in the fluid media of the body, but also is related to a change in the kidneys' sensitivity to them. PMID- 6254580 TI - Prostaglandins, steroids and reception (an attempt to model the structure of the active centers of adrenoreception). AB - On the basis of numerous results of investigations on adrenergic systems, an orientational model of the adrenoreceptor (AR) is postulated. Its active center includes low-molecular-weight components--prostaglandins (PGE, PGF), steroids (cortisone, hydrocortisone), S+-adenosylmethionine, Ca, Mg, and Mn ions. Appraisal of the stereospecific characteristics of such a functional unit of AR explains the difference in the nature and magnitude of the effects of interaction of the catecholamines, their agonists and antagonists will the so-called alpha- and beta-AR. Depending on the organ or tissue in which the AR is located, its protein subunits comprise adenylcyclase (beta-AR) or Na,K-ATPase (alpha-AR). An obligatory component of the AR is catechol-O-methyltransferase. The model elaborated describes satisfactorily the molecular mechanisms of action of many pharmacological agents, explains why attempts to isolate and reconstruct the AR have proved fruitless, and gives grounds for rejecting the hypothesis that there exist steroid, prostaglandin, and purinergic receptors, linking the exceptionally high and diverse activity of these biologically active substances with their participation in adrenoreception among other reasons. A conception of the active centers of the AR as low-molecular-weight entities permits the explanation of such phenomena as the desensitization of the AR, the "interconversion" of beta-AR into alpha-AR with a change in the parameters of the medium, and certain components of the pathogenesis of bronchial asthma, etc. PMID- 6254581 TI - Unusual nuclear inclusions in four nerve biopsies. An ultrastructural study. AB - The authors have reported four cases where the study of peripheral nerve biopsy revealed the presence of abnormal cells in the endoneurial space. Their bulky nuclei contain in fact numerous deposits more or less tubular reminiscent of the intranuclear structures observed in the multiple sclerosis brains, and other very rare diseases. Exceptionally it seems have these images been described in peripheral nerves. It must be stressed that only one patient had an inflammatory type disease. The meaning of these images is discussed, though no definite conclusion could be reached. PMID- 6254582 TI - A 13C NMR spin-lattice relaxation study of the interaction of myelin proteins with ipid vesicles. PMID- 6254583 TI - Crotalocytin: characterization of the timber rattlesnake platelet activating protein. AB - Crotalocytin, a platelet activating protein from timber rattlesnake venom, was studied to characterize its nature and to investigate its action on platelets. It exhibited proteolytic activity on the substrate azocoll and amidolytic activity on several peptide p-nitroanilides. The platelet activating and amidolytic activity of Crotalocytin was inhibited by diisopropylfluorophosphate. In addition, phenylmethylsulfonyl fluoride inhibited Crotalocytin's ability to stimulate platelets. Active site titration with p-nitrophenyl guanidobenzoate indicated that 52% of Crotalocytin's molecules were active and that the enzyme could also hydrolyze the titrant. These studies showed that Crotalocytin is a serine protease. Like thrombin and collagen, Crotalocytin induced simultaneous platelet aggregation and adenosine triphosphate (ATP) secretion. EDTA and prostaglandin E (PGE1) blocked Crotalocytin's ability to activate platelets; hirudin and antithrombin III did not. Crotalocytin stimulated the secretion of serotonin from dense granules and low affinity platelet factor 4 and fibrinogen from alpha-granules. Crotalocytin did not cause platelet lactic dehydrogenase loss or agglutinate formalin-fixed platelets, but it did aggregate chymotrypsin treated platelets. Studies with antimycin A and 2 deoxy- D-glucose showed that Crotalocytin-induced platelet secretion was dependent on metabolic energy. Furthermore, Crotalocytin's induction of platelet secretion was prevented by eliminating exogenous ADP and blocking activation of the arachidonate pathway. Timber rattlesnake venom contains a serine protease that is unique, potent platelet activator. PMID- 6254584 TI - Organization of alpha-globin genes in Hb Hasharon (alpha 47 asp replaced by his) carriers. AB - Restriction enzymes analysis of the DNA from two unrelated Italian families with Hb Hasharon, a variant Hb (alpha 47asp replaced by his) frequently occurring in the Polesine area in Italy, indicates that this variant is associated to an alpha globin gene deletion. The alpha Hash genotype most likely results from a mutation on an alpha thal2 genotype. PMID- 6254585 TI - Distribution and localization of adenosine 3':5'-monophosphate-dependent protein kinase in mammalian artery. AB - Among the three major vascular layers (the intima-inner, the media-middle smooth muscle, and the adventitia-outer connective tissue) over 90% of the total protein kinase activity was observed in the middle layer. Of various subcellular fractions of the vascular smooth muscle, the 105,000 g supernatant (cytosol fraction) showed the highest specific activity and represented more than two thirds of the total kinase present in this layer. DEAE-cellulose chromatography of the soluble enyzme revealed the existence of two major forms of cyclic AMP dependent protein kinase, type I and type II, of which 60% of the total enzymatic activity was found in type II. A divalent cation was found to be essential for their phosphotransferase activity. Only Mg2+ and Co2+, but not Zn2+, Mn2+ or Ca2+ could satisfy the cation requirement. The phosphorylated substrate had the characteristics of a protein with a phosphoester bond. PMID- 6254586 TI - Involvement of a central alpha-adrenoceptor system in antidepressant potentiation of hyperthermia induced by thyrotropin releasing hormone. AB - Thyrotropin releasing hormone (TRH) causes hyperthermia in mice which is potentiated by tricyclic antidepressants (nortriptyline, imipramine, clomipramine, amitriptyline), the monoamine oxidase inhibitor, tranylcypromine, and various other antidepressants (maprotiline, nomifensin, viloxazine). Only iprindole is ineffective. The effect of mianserin, itself hypothermic, could not be interpreted. A property shared by the potentiating substances seems to be activation of a central adrenoceptor system. The potentiation of TRH-induced hyperthermia which seems to be specific to antidepressants might be used in the selection of antidepressants. PMID- 6254587 TI - Effects of arachidonic acid on rat gastric acid secretion in response to different secretogogues; inhibition of these effects by indomethacin. AB - 1 The effects of the prostaglandin precursor, arachidonic acid, and the non steroidal anti-inflammatory drug, indomethacin, on gastric acid secretion were studied in the rat, in vivo and in vitro. Gastric mucosal blood flow was also measured in vivo. 2 Arachidonate produced significant inhibition of acid secretion stimulated by pentagastrin or histamine. It did not significantly affect dibutyryl cyclic adenosine 3',5'-monophosphate (db cyclic AMP)-induced acid secretion. 3 Inhibition of acid secretion by arachidonate was accompanied by a rise in the ratio of mucosal blood flow to acid secretion. 4 Indomethacin did not significantly alter histamine- or pentagastrin-induced acid secretion. 5 In the presence of indomethacin, the inhibitory effect of arachidonate was significantly reduced. 6 These results provide evidence that the rat gastric mucosa is capable of synthesizing, from exogenous precursor, products of cyclo oxygenase which inhibit gastric acid secretion. PMID- 6254588 TI - An electrophysiological analysis of the effects of morphine on the calcium dependence of neuromuscular transmission in the mouse vas deferens. AB - 1 The effects of morphine on the Ca-dependence of the synaptic potential amplitude in the mouse vas deferens have been determined. 2 The synaptic potential increased with a power factor of 2.4 for [Ca]o between 0.7 mM and 1.8 mM. Morphine (40 nM) decreased the synaptic potential, without altering the second power relationship between the synaptic potential and [Ca]o. 3 Morphine reversed the depression in the synaptic potential which develops during a short high-frequency (10 Hz) train of impulses to facilitation. Consequently the synaptic potential beyond the tenth impulse was unaffected by morphine. 4 Morphine did not alter the facilitation of the synaptic potential which develops during a short low-frequency (less than or equal to 2 Hz) train of impulses in normal [Ca]o. Consequently morphine decreased the synaptic potential for each impulse by about the same percentage amount. 5 Morphine increased the small facilitation in the synaptic potential which occurs during a short low-frequency (less than or equal to 2 Hz) train of impulses in high [Ca]o. This facilitation approximated the predictions based on the assumption that each impulse leaves residual Ca ions bound to receptors involved in transmitter release from the nerve terminal. PMID- 6254589 TI - Adverse effects of artificial buffers on contractile responses of arterial and venous smooth muscle. AB - 1 In vitro studies were undertaken on rat aortic strips and portal vein segments in order to determine whether or not several commonly used artificial buffers, i.e., tris(hydroxymethyl) aminomethane (Tris), N-2-hydroxyethylpiperazine-N'-2 ethanesulphonic acid (HEPES), morpholine propanesulphonic acid (MOPS), N,N bis(2 hydroxyethyl) glycine (BICINE) and 1,4-piperazinediethanesulphonic acid (PIPES), can exert direct actions on vascular smooth muscle. 2 All artificial buffers used in 5 mM concentrations were found to inhibit development of spontaneous mechanical activity. 3 Tris, HEPES, MOPS, BICINE and PIPES markedly attenuated contractions induced by adrenaline, angiotensin and KCl. The fast phase components of the agonist-induced contractions were either obliterated or reduced in the presence of the artificial buffers. The sustained slow phase components were greatly reduced and retarded by the artificial buffers. 4 The relative order of artificial buffer potency (i.e., from 100% to 14% inhibition) seems to depend upon the agonist and type of smooth muscle. 5 All of these inhibitory effects were reversible, since normal contractile responses and spontaneous mechanical activity could be obtained by simply reincubating the smooth muscles in Krebs Ringer bicarbonate buffer. 6 A variety of pharmacological antagonists failed to mimic or affect the inhibitory effects of Tris, HEPES, MOPS, PIPES and BICINE. 7 These data show that five of the most commonly used artificial buffers, to study muscles in vitro, exert adverse effects on contractility of arterial and venous smooth muscle. PMID- 6254590 TI - Post-tetanic potentiation in ganglia which are blocked with hexamethonium. AB - 1 Post-tetanic potentiation (p.t.p.) of the compound action potential in the presence of hexamethonium was observed in the isolated stellate ganglion of the hamster using extracellular postganglionic recordings. 2 The magnitude of the p.t.p. was small (less than a 20% increase) in the control solution, but increased as the depth of blockade with hexamethonium was increased. 3 The magnitude of the p.t.p. was frequency-dependent between 1 and 40 Hz. 4 Atropine partially blocked the p.t.p. 5 McN-A-343, a muscarinic agonist, potentiated ganglionic transmission which had been partially blocked by hexamethonium. 6 Repetitive stimulation in the presence of hexamethonium potentiated the discharges induced by DMPP, a nicotonic agonist. The potentiation was blocked by atropine. 7 It was concluded that the p.t.p. in the presence of hexamethonium has the same characteristics as p.t.p. in the control solution. There appears to be both a muscarinic component and a presynaptic component of the p.t.p. PMID- 6254591 TI - Biological effects of degradation products of collagen by bacterial collagenase. AB - 1 Collagen degradation products (CDP) resulting from bacterial collagenase digestion were fractionated by gel filtration and their biological activities in rats were estimated. 2 CDP induced the following kinin-like effects: increase in permeability of skin blood vessels, contraction of the isolated intestine of the rat, depression of locomotor activity and of motor coordination. 3 The most active CDP fraction was CDP III containing peptides of mol. wt. < 1000 D with a high percentage of hydroxyproline. 4 As compared with bradykinin, CDP III was less active in the skin permeability test and was 15,000 to 20,000 fold less effective in induction of isolated intestine contraction. 5 Depression of the CNS induced by 30 microgram of CDP III administered into the brain ventricle was similar to that observed after 4 microgram of bradykinin given by the same route. 6 CDP III prolonged the duration of sleep evoked by thiopentone and enhanced the threshold of convulsion induced by pentazol. 7 The activity of CDP in comparison to other low molecular weight peptides is discussed. PMID- 6254593 TI - Release of prostaglandin E from the isolated urinary bladder of the guinea-pig. AB - 1 Release of prostaglandin E (PGE) from guinea-pig urinary bladder in vitro has been demonstrated both in the resting state and during electrical stimulation. 2 The electrically evoked release of PGE was significantly higher than the resting release and was frequency-dependent. 3 The released substance was characterized as PGE pharmacologically by (a) blockade of its response by SC-19220 on guinea pig ileum, (b) reduction of the amount of the released substance by indomethacin and (c) the inhibitory effect of the released substance on adrenergic neurotransmission in guinea-pig vas deferens. 4 The prostaglandin seemed to originate from the muscle since tetrodotoxin treatment did not abolish the release during direct muscle stimulation; however, concomitant release from neuronal tissue could not be excluded in the present experiments. 5 Indomethacin failed to inhibit the mechanical responses of the bladder to transmural stimulation. 6 The present experiments suggest that PGE is not involved in mediating the non-cholinergic non-adrenergic neurotransmission in the guinea-pig urinary bladder. PMID- 6254592 TI - alpha-Sympathomimetic amines and calcium-mediated action potentials in guinea-pig ventricular muscle. AB - 1 The ability of amines, having alpha- or alpha- and beta-adrenoceptor stimulating activity, to restore excitability and contractility in heart preparations partially depolarized by potassium, was investigated in guinea-pig ventricular muscle in order to elucidate the mechanism of the positive inotropic effect mediated via alpha-adrenoceptors. 2 In preparations in which fast sodium channels were inactivated by K+-rich medium (22 mM) slow electrical responses as well as contractions were consistently induced by high concentrations of phenylephrine (10(-4) to 3 X 10(-4) M) and synephrine (3 X 10(-4) M). 3 The restorative effective effects of both phenylephrine and synephrine were unaffected by phentolamine (10(-5) M) but were readily abolished by practolol (10(-5) M) or sotalol (10(-5) M). 4 Methoxamine induced a dose-dependent positive inotropic effect in ventricular strips paced at 0.5 Hz in normal Tyrode solution; the maximum increase in contractile tension was obtained with methoxamine 10(-4) M. However, at the same concentration, the amine did not induce slow electrical responses in potassium-depolarized preparations. 5 It is concluded that the induction of slow responses by phenylephrine and synephrine is due to beta adrenoceptor stimulation, and that the increase in cardiac contractility caused by alpha-adrenoceptor stimulation does not involve an increase in slow inward calcium current. PMID- 6254594 TI - Rate, force and cyclic adenosine 3',5'-monophosphate responses to (--)-adrenaline in neonatal rat heart tissue. AB - 1 (-)-Adrenaline sensitivity in 1 to 20 day-old rat heart tissue was investigated as rate, force and cyclic adenosine 3',5'-monophosphate (cyclic AMP) production responses together with sensitivity to (+/-)-propranolol blockade.2 Resting performances were measured and responsiveness to (-)-adrenaline then determined as ED(50) values and maximal responses together with sensitivity to propranolol (pA(2) values).3 Resting force, corrected for sample size, did not change with age, whereas resting atrial rate doubled between 1 and 20 days.4 ED(50) concentrations in atria were constant with age, but decreased in ventricles. Cocaine (10(-5) M) and other drugs did not consistently affect ED(50) values.5 Maximal responses were not age-dependent in right atria, but increased in left atria. In 2 to 5 day-old hearts there was no inotropic response to adrenaline and the very small maximal response in ventricles rose 5 to 7 fold by 20 days.6 Propranolol sensitivity increased slightly (2 to 4 times) with age in all tissue from a pA(2) value of 7.5 at 2 days to 8.2 at 20 days.7 Control cyclic AMP was higher in 2 day than in 20 day-old tissue and in atria than ventricular strips or hearts. In 2 and 20 day-old atria, hearts and ventricles, force increases with different adrenaline concentrations correlated linearly with the log of the increase in cyclic AMP. Such a correlation was not seen in 2 day hearts and ventricles for cyclic AMP rose without corresponding force increases.8 Results suggest slight maturational changes in atrial beta-receptors. In 1 to 5 day-old ventricles, normal ED(50) concentrations and good cyclic AMP response in the presence of a much reduced force response may indicate receptor-response transduction inefficiency, assuming a beta(1)-receptor occupation and cyclic AMP production response mechanism for inotropism with adrenaline. PMID- 6254595 TI - Facilitation of sympathetic neurotransmission in the rat anococcygeus muscle by prostaglandins D2 and F2 alpha. AB - 1 Investigations were made into the effects of prostaglandins D2 (PGD2) and F2 alpha (PGF2 alpha) on the responses of the rat anococcygeus muscle to field stimulation of intrinsic motor (sympathetic) and inhibitory nerves, and to exogenous noradrenaline. 2 PGD2 (2.8 X 10(-6) mol/1) substantially increased the motor responses to field stimulation at all frequencies tested (2 to 32 Hz), and caused a smaller increase in the responses to noradrenaline. 3 PGF2 alpha (2.8 X 10(-6) mol/1) strongly potentiated the motor responses to field stimulation (2 to 32 Hz) and also to noradrenaline. This prostaglandin had quantitatively similar effects on the responses to both types of stimulus. 4 PGD2 was without effect on the inhibitory responses evoked by field stimulation in the presence of guanethidine. PGF2 alpha seemed to reduce the inhibitory responses to low frequencies of stimulation (0.5 to 1.5 Hz), but this effect was marginal. 5 The results suggest that PGD2 facilitates sympathetic neurotransmission in this tissue by both pre- and post-junctional actions. The effect of PGF2 alpha seems likely to be mediated predominantly post-junctionally. PMID- 6254596 TI - Structure-activity relationships of clonidine- and tolazoline-like compounds at histamine and alpha-adrenoceptor sites. AB - 1 Thirty clonidine- and tolazoline-like compounds with differing phenyl ring substituents were tested for agonistic actions at histamine H1-receptors (guinea pig ileum), histamine H2-receptors (guinea-pig driven right ventricular strips), post-junctional alpha-adrenoceptors (rat desheathed was deferens) and pre junctional alpha-adrenoceptors (inhibition of sympathetic stimulation in guinea pig driven left atria). 2 All compounds were inactive at histamine H1-receptors, while 21 of the 30 compounds displayed varying stimulant activity at H2 receptors. 3 At post-junctional alpha-receptors all 30 compounds produced stimulant actions, whereas at prejunctional alpha-receptors the compounds displayed either agonistic or antagonistic actions. 4 Thus structure-activity relationships (SAR) could only be validated for histamine H2- and post-junctional alpha-receptor effects. These studies show that the most potent compounds are those with 2,6-phenyl substituents in which rotation is restricted so that the two rings are aplanar. Electronic effects of the substituents have a greater influence on activity at H2- than at alpha-receptors. 5 The major difference in SAR involves the influence of substituents in the 3, 4 or 5 positions on the phenyl ring. The presence of these substituents abolish significant activity at H2-receptors, while alpha-receptor stimulant activity is retained. PMID- 6254598 TI - The effects of acute and chronic ethanol administration and its withdrawal on gamma-aminobutyric acid receptor binding in rat brain. AB - 1 The effects of acute and chronic ethanol administration, and withdrawal on the binding of the inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), was investigated in rat brain. 2 Acute ethanol (2 to 4 g/kg i.p. 30 min before removal of brain) produced an increase in the binding capacity of the low affinity GABA receptor binding site. 3 Following chronic ethanol administration (1 to 21 days), the GABA receptor binding characteristics were not altered. These results suggest a possible adaptation of GABA receptors to the continuous presence of ethanol at the GABA synapse. 4 During ethanol withdrawal, the affinity of the low affinity GABA receptor binding site was significantly lower than pair-fed controls at 8 and 16 h withdrawal. 5 These results suggest that GABA receptor sensitivity may play a role in some of the neuropharmacological effects of ethanol and in its withdrawal symptoms. PMID- 6254597 TI - Pharmacological differentiation of presynaptic inhibitory alpha-adrenoceptors and opiate receptors in the cat nictitating membrane. AB - 1 The action of morphine, naturally occurring and synthetic opiate peptides on [3H]-noradrenaline release induced by nerve stimulation was studied in the isolated nerve muscle preparation of the cat nictitating membrane under experimental conditions in which the alpha-presynaptic receptors were blocked by phentolamine 1 microM. 2 Morphine and the naturally occurring peptides: [Met5] enkephalin, [Leu5]-enkephalin and beta-endorphin reduced 3H-transmitter overflow and responses to nerve stimulation from the cat nictitating membrane, effects which were completely antagonized by naloxone 0.3 microM. The relative order of potency for the inhibition of the stimulation-induced 3H-transmitter overflow at the level of the IC50 (microM) was as follows: [Met5]-enkephalin (0.020 microM) greater than or equal to [Leu5]-enkephalin (0.036 microM) > morphine (0.3 microM) > beta-endorphin (1 microM). 3 The synthetic opiate pentapeptides: BW 180 C (Tyr D-Ala-Gly-Phe-D-Leu), and BW834 C (Tyr-D-Ala-Gly-pClPhe-DLeu), which are resistant to enzymatic degradation were more potent than the enkephalins in reducing the stimulation-evoked transmitter overflow from the cat nictitating membrane. On the other hand, the tetrapeptide BW832 C, which lacks the D-leucine terminal of BW180 C l was less potent than the enkephalins in inhibiting neurotransmission. 4 In the presence of phenoxybenzamine 1 microM, 3H-transmitter overflow was increased 8 fold and the inhibition of neurotransmission by methionine-enkephalin was not affected. Exposure to phenoxybenzamine 10 microM increased [3H]-noradrenaline overflow 15 fold and antagonized the effects of methionine enkephalin on transmitter release. 5 In the cat nictitating membrane the inhibitory presynaptic opiate receptors are different from the presynaptic alpha-autoreceptors which regulate the release of noradrenaline elicited by nerve depolarization through a negative feed-back mechanism. PMID- 6254600 TI - Thermoregulatory effects of N6-2'-Q-dibutyryl adenosine 3',5'-monophosphate in the restrained mouse. AB - 1 The N6-2-O-dibutyryl derivative of adenosine 3',5'-monophosphate (db cyclic AMP) has been micro-injected into the third cerebral ventricle of the unanaesthetized, restrained mouse and the effects on body temperature and thermoregulatory activities observed. 2 Db cyclic AMP (4, 16 and 32 micrograms) injected intracerebroventricularly produced hypothermia when compared with temperature responses to sodium n-butyrate (6.8 micrograms). 3 Hypothermia induced by db cyclic AMP in mice was associated with a fall in oxygen consumption together with behavioural and autonomic heat loss activities but not cutaneous vasodilatation. The effects on rectal temperature and oxygen consumption were dose-dependent. 4 The falls in rectal temperature and oxygen consumption induced by db cyclic AMP (4 micrograms) were decreased by elevation of the environmental temperature from 22 to 32 degrees C and abolished at 36 degrees C. 5 It is concluded db cyclic AMP may inhibit central events mediating the rise in metabolic heat production in mice upon exposure to cold environments. PMID- 6254599 TI - Effects of RMI 12330A, a new inhibitor of adenylate cyclase on myocardial function and subcellular activity. AB - 1 RMI 12330A, a lactam-imine, at concentrations of 10(-4) M and higher, inhibited basal as well as isoprenaline and NaF-stimulated adenylate cyclase activity of guinea-pig heart homogenates. However, RMI 12330A was a more potent inhibitor of histamine-stimulated adenylate cyclase (IC50 of 1.5 X 10(-5) M). 2 In the isolated work-performing heart of the guinea-pig, RMI 12330A (IC50 of 1.1 X 10( 6) M) depressed all cardiac functions: pressures developed, dP/dt, contractile force, dF/dt, work performance and stroke work. Left atrial pressure rose and the positive inotropic response to increasing heart rate (staircase) became negative. Histamine, isoprenaline and ouabain no longer caused positive inotropic effects. 3 Increasing the perfusate calcium concentration from 2.5 mM to 4.5 and 6.5 mM completely restored cardiac function after its depression by RMI 12330A. 4 RMI 12330A uncoupled mitochondrial oxidative phosphorylation; the classical uncoupler, dinitrophenol, had the same effects on cardiac dynamics as RMI 12330A. 5 RMI in high doses inhibited hydrolytic activity of Na+, K+-ATPase of crude and purified heart preparations (IC50 of 1.7 X 10(-4) M) and inhibited ouabain binding to the same enzymes (IC50 of 1.5 X 10(-4) M). 6 A lactam-imine analogue of RMI 12330A that had no effect on adenylate cyclase, was also without effect on any of the systems examined. PMID- 6254601 TI - Drugs and rheumatoid arthritis. PMID- 6254603 TI - Management of patients after self-poisoning. PMID- 6254602 TI - Comparison of various treatments for irritable bowel syndrome. AB - A previous therapeutic trial of factorial design showed that a combination of a psychotropic drug, a smooth-muscle relaxant, and a bulk former (lorazepam, hyoscine hydrobromide, and ispaghula husk) relieved symptoms of the irritable bowel syndrome more effectively than the same agents given singly. Another trial of similar design was undertaken to compare each of these three agents with another having the equivalent clinical actions--namely, Motival (fluphenazine/nortriptylene mixture), mebeverine, and bran. Ninety-six patients took part; all received three agents, one from each of the three pairs being compared, and no placebos were used. Fifty-six patients reported a sustained symptomatic improvement, which was a significantly higher incidence than in the previous trial, when placebos were used. Ispaghula was significantly more effective than bran. The combination of ispaghula, Motival, and mebeverine improved 11 out of 12 patients--significantly more than bran, Motival, and hyoscine (five improved), or bran, lorazepam, and mebeverine (four improved). Mebeverine was significantly more effective when combined with Motival (18 out of 24 improved) than with lorazepam (10 improved). These results confirm the value of a combined therapeutic approach to the relief of the irritable bowel syndrome and suggest the possibility of synergism between agents. PMID- 6254604 TI - Spontaneous disappearance of psoriasis as presenting feature of oat-cell carcinoma of lung. PMID- 6254605 TI - Calmodulin. PMID- 6254606 TI - Spontaneous abortion after hand-foot-and-mouth disease caused by Coxsackie virus A16. PMID- 6254607 TI - Food for thought. PMID- 6254608 TI - Site of action of intrathecal morphine. PMID- 6254609 TI - Paraesthesiae from ectopic impulse generation in human sensory nerves. AB - Intraneural microelectrode recordings were obtained from sensory nerve fascicles in awake normal subjects experiencing post-ischaemic paraesthesiae. Spontaneous activity in afferent fibres started about half a minute after re-establishment of circulation; it peaked by the second minute and slowly waned thereafter. This parallelled the time course and intensity of the perceived paraesthesiae. During the most intense stage of paraesthesiae, single unit discharges consisted of prolonged bursts of high-frequency impulses (200-300 imp/s) lasting for 1 to 7 seconds. Repeated bursts became progressively shorter and often exhibited marked rhythmicity as paraesthesiae became weaker. Hyperventilation increased paroxysmal firing and paraesthesiae, whereas ischaemic periods repeated at short intervals exhausted the impulse generating mechanism. The outcome of local anaesthetic blocks indicated that the impulses were generated ectopically along the nerve fibres previously subjected to ischaemia and not primarily from the receptors in the skin. The high frequency of the discharge and the quality and distribution of various paraesthesiae suggest that sensory units with myelinated fibres participated in the paroxysmal discharge; normal activity, but no ectopic discharges were recorded in unmyelinated fibres. It is proposed that the perverted quality of paraesthesiae is due to an abnormal spatio-temporal pattern of ectopic impulses from different types of sensory units. creating a chaotic percept consisting of an assortment of sensations referred in irregular succession to multiple areas. PMID- 6254610 TI - An autoradiographic study of human gliomas: growth kinetics of anaplastic astrocytoma and glioblastoma multiforme. AB - When 3H-thymidine was administered either intravenously or intra-arterially to 9 patients with gliomas (5 glioblastoma multiforme, 3 anaplastic astrocytoma, and one mixed glioma) shortly before operation, and tissue obtained from the biopsy and, subsequently, at autopsy was examined by autoradiography, it was found that 2 of the glioblastomas diluted out the labelling in the two- to four-month interval between labelling and autopsy, whereas 3 other glioblastomas and the 2 anaplastic astrocytomas retained labelled neoplastic cells in parts of the tumours at autopsy after intervals of from three weeks to five months following labelling. Most patients whose tumours demonstrated foci of labelled cells at autopsy survived longer (1.5 to 7 years). Certain neoplastic cells in anaplastic astrocytomas and some glioblastomas appear either to limit cell division or to differentiate even in an environment favourable to cell proliferation. PMID- 6254611 TI - Effects of carnosine on olfactory bulb EEG, evoked potentials and DC potentials. AB - Carnosine is a dipeptide found in great quantities in the primary olfactory nerve and has been suggested to be the neurotransmitter of the olfactory receptor axons. The aim of the present study was to describe some of its electrophysiological actions in the olfactory bulb (OB) of rabbits under anesthesia. Carnosine as a 10% solution in amounts of 2-5 microliter was injected to the OB at the level of the glomerular layer by means of a pipette attached to a Hamilton syringe. Average evoked potentials (AEPs) on the stimulation of the lateral olfactory tract (LOT-AEP), electroencephalographic (EEG) activity and slow potential (DC) recordings were obtained. The LOT-AEPs were analyzed by fitting damped sine waves to them. The parameters of amplitude, frequency, decay rate, phase and rise rate were measured and statistically compared to the values obtained prior to the carnosine injection. An increase in frequency and decreases in the phase and the decay rate of the AEP were found. Carnosine also produced a sustained oscillation in the EEG and a surface negative, deep positive shift in the DC recording. The changes were maximal within the first minute after injection and lasted 2-7 min. Tyrodes' solution, which was used as the carnosine vehicle, did not produce any changes, nor did beta-alanine, which is one of the constituents of carnosine, at equivalent osmotic concentrations. It is concluded that carnosine has an excitatory action on the mitral/tufted cells, and that this effect is obscured by a secondary increase in granule cell (inhibitory) activity. PMID- 6254612 TI - Metabolic changes induced in rat hippocampal slices by norepinephrine. AB - The oxidative metabolic activity of restricted regions of hippocampal slices was assessed by a continuous measurement of the fluorescence of intramitochondrial nicotinamide-adenine dinucleotide (NADH). A large increase in NADH fluorescence was triggered by substituting the oxygen supply to the slice by nitrogen gas. A large and transient increase in NADH fluorescence was also produced by superfusion of the the slice with a high (50 mM) potassium-containing medium. Addition of norepinephrine (NE) to the superfusion medium caused a propranolol inhibited increase in NADH fluorescence. Furthermore, ouabain, which inhibits the Na-K pump, blocked the effects of NE. An analog of cyclic adenosine monophosphate (cAMP), 8-bromo cAMP, mimicked the effect of NE. Finally, effects of NE could still be produced in a kainic acid-treated hippocampus, where most neurons were previously destroyed by the drug. It is suggested that NE activates a Na-K ATPase, that this effect might be mediated by cAMP, and that these interrelations may underly the physiological action of NE in the brain. PMID- 6254613 TI - Properties of two temperature-sensitive Rous sarcoma virus transformed cerebellar cell lines. AB - Cells from the cerebellum of 3-day-old BD-IX rats were obtained as permanent lines by transforming them with temperature-sensitive Rous sarcoma virus. The presence or absence of veratridine-stimulated Na+-uptake (voltage-dependent channels) was used to operationally classify them as neuronal or glial. When incubated at 34 degrees C, the permissive temperature for transformation, the cerebellar cells exhibit a transformed phenotype determined by anchorage independence, rounded morphology, high growth rate and absence of density dependent inhibition of growth. In contrast, when the transformed cerebellar cell lines are kept at a temperature (38 degrees C) non-permissive for transformation, they exhibit a normal cellular phenotype with respect to the above properties. Moreover, changes toward neuronal morphology, increase in veratridine-stimulated Na+-uptake, decreased growth rate and the expression of the astrocyte specific protein, glial fibrillary acidic protein, suggest that a degree of differentiation is expressed at the non-permissive temperature. PMID- 6254614 TI - Increased feeding and hyperglycemia elicited by intracerebroventricular 5 thioglucose. AB - 5-Thioglucose (5-TG) is a glucose analogue in which sulfur is substituted for the pyranose ring oxygen. Intracerebroventricular infusion of 5-TG caused prompt initiation of feeding and a marked rise in plasma glucose concentration at doses as low as 0.54 mumol (106 microgram). 5-TG is, therefore, more potent for eliciting feeding than any other previously tested glucose antimetabolite. The potency of 5-TG for eliciting feeding should make 5-TG a useful tool for localizing brain glucoreceptors which participate in the control of food intake. PMID- 6254615 TI - Modulation of transmission in flexion reflex pathways by knee joint afferent discharge in the decerebrate cat. AB - In the intact hindlimb, flexion reflexes are most easily obtained when the knee is extended. Movement of the knee joint after the muscles have been tenotomized and held at fixed lengths still modulates flexion reflex excitability. After anaesthesia of the joint capsule movement of the limb no longer affects flexion reflex excitability. PMID- 6254616 TI - Inhibition of the action of cholecystokinin octapeptide on the guinea pig ileum myenteric plexus by dibutyryl cyclic guanosine monophosphate. PMID- 6254617 TI - [Effect of age on the activity of lysosomal enzymes in human polymorphonuclear leukocytes (author's transl)]. PMID- 6254618 TI - [Adrenomyeloneuropathies]. AB - An adrenomyeloneuropathy is observed in a patient died at 24 years old after an illness of five years duration. These case is peculiar by the presence of lamellar cytoplasmic inclusions in the Schwann cells. Adrenomyeloneuropathy is an adult variant of adrenoleucodystrophy. This sex linked recessive disorder is related to an excessive amount of long chain fatty acids. PMID- 6254619 TI - [Ultrastructural study in the diagnosis of various neurolipidoses]. AB - We have studied the sphingolipidosis, principally, ceroid-lipofuscinosis and other complex lipid storage diseases. We examined biopsy tissue of fourteen patients with diseases of the various types given above. The biopsy tissue was usually skin, muscle or peripheral nerve, and occassionally brain or various visceral tissue. PMID- 6254620 TI - [Biochemical and pharmacological approach to the functional disorders observed in demyelination mutants (GABAergic and noradrenergic systems)]. AB - The abnormal behavior observed in diseases of myelin remains unexplained. Mutations in the mouse in which the main phenotypic expression involves myelination is a useful tool. As tonic seizures are observed, an electrophysiological, pharmacological and biochemical study was performed. The convulsions seem to be linked mainly to an alteration of the alpha-adrenergic system. The GABA-ergic system is also modified. The relations between these observations and the defect of myelination remain to be elucidated. PMID- 6254622 TI - [A molecular abnormality of the erythrocyte membrane in beta-thalassemia]. AB - We present a new abnormality of the red cell membrane observed in the course of a study on beta-thalassemia. In a child suffering from a beta 0-thalassemia major, the neutral membrane bound phosphatase, instead of having Michaelis-Menten kinetics, displayed a biphasic kinetics consistent with inhibition by substrate excess. This abnormality is discussed along with other erythrocyte membrane alterations that are known to occur in beta-thalassemia. PMID- 6254621 TI - [Sulfatide: a multifunctional glycolipid constituent of biological membranes]. AB - Sulfogalactosylceramide (or sulfatide) has been localized in the central nervous system by indirect immunofluorescence. This glycosphingolipid belongs essentially to the myelinated areas. Nevertheless, it has also been found in ependymal cells, subpial processes and, in the cerebellum, in the Bergmann fibers. In the brain areas, known to be enriched in opiate receptors, some cells and nerve terminals are also sulfatide positive. In this latter localization, opiates were shown to selectively inhibit binding of the antisulfatide antibodies. We have also shown that antisulfatide inhibited, in vitro, the stereo-specific binding of narcotic drugs and that they antagonized the in vivo effects of morphine and beta endorphin. PMID- 6254623 TI - [Mechanism(s) of neoplastic transformation by avian oncogenic retroviruses]. AB - Neoplastic transformation by avian oncogenic retroviruses, notably by sarcoma viruses, the best known of all, results from the expression of a specific viral gene (oncogene), presumably of cellular origin. The protein coded for by this gene appears to act on different targets controlling the various modified cellular characters. A proteic factor coded for by the cell, and derepressed or activated by the expression of the oncogene, is involved in the maintenance of morphological transformation. This factor is also produced by cells transformed by other viruses or oncogenic agents. Other cellular factors, derepressed or activated, may also act as effectors for other parameters of transformation. PMID- 6254624 TI - [Origin of the transforming genes in avian acute leukemia retroviruses]. AB - The avian defective leukemia viruses are recombinants between an avian virus of low oncogenicity and specific host nucleotide sequences. The types of hematological neoplasms correlate with the specificity of the sequences transduced. These could be differentiation genes escaping cellular control after their transduction by the virus. PMID- 6254625 TI - Powassan virus encephalitis in southeastern Ontario. PMID- 6254626 TI - Dietary fibre and colon cancer: epidemiologic and experimental evidence. AB - Epidemiologic studies have identified two dietary factors, a relatively high intake of fat and a relatively low intake of fibre, that are associated with colon cancer in humans. However, a recent study has shown a low risk of large bowel cancer in a rural Finnish population with a high dietary intake of fat, but also a high intake of fibre. Observations in humans and studies in animals have indicated that dietary fibre may protect against colon carcinogenesis by binding bile acids in the intestinal tract, by a direct effect on the colonic mucosa and by an indirect effect on the metabolism of carcinogens. The strength of protection varies with the type of fibre. PMID- 6254627 TI - Sporadic bovine leukosis: a description of eight calves received at Animal Diseases Research Institute from 1974-1980. AB - Eight calves with sporadic bovine leukosis are described. The common features were generalized lymphadenopathy, visceral involvement and raised total leukocyte and lymphocyte counts. Agar gel immunodiffusion tests for bovine leukemia virus antibodies were negative in eight animals and in all animals from three herds of origin. Lymphocytic nuclear pockets were found in the tissues of one calf but attempts to isolate bovine leukemia virus from two animals were unsuccessful. PMID- 6254628 TI - Surgical resection of perforated abomasal ulcers in calves. AB - Surgical resection of perforating abomasal ulcers was successful in four of ten suckling calves. Mortality, usually occurring within 48 hours, was attributed to diffuse fibrinopurulent peritonitis, toxemia and shock. PMID- 6254629 TI - Combination chemotherapy, radiotherapy, and BCG immunotherapy in extensive (metastatic) small cell carcinoma of the lung. A Southwest Oncology Group study. AB - From November 1976 to November 1978, the Southwest Oncology Group treated 254 patients with extensive (metastatic) small cell carcinoma of the lung with combination chemotherapy and radiotherapy with and without BCG immunotherapy. Patients receiving BCG achieved a response rate of 50% versus those patients not receiving BCG of 46% (P = .704). Response duration was 20 weeks for the BCG arms and 23 weeks for the no-BCG arms; survival was 28 weeks for the BCG arms versus 29 weeks for the no-BCG arms. An adverse effect in patients surviving more than one year was detected; those continuing to receive BCG had significantly shorter survival, 60 weeks versus 85 weeks (P = .019). Toxicities of the programs were not affected by the addition of BCG immunotherapy. It appears that BCG immunotherapy has no beneficial effect on response rate or duration of response in programs using chemotherapy and radiotherapy for control of metastatic small cell carcinoma of the lung. In addition, because of the adverse effect on long term survival, we do not recommend the addition of BCG immunotherapy as a treatment modality in this tumor type. PMID- 6254630 TI - Surgical adjuvant chemotherapy with mitomycin C and cyclophosphamide in Japanese patients with breast cancer. AB - A controlled trial of surgical adjuvant chemotherapy for breast cancer was carried out using 551 Japanese patients. Single or combined treatment with mitomycin C (0.2 mg/kg i.v. three times within five days postoperatively) and cyclophosphamide (100 mg postoperatively daily for four months or longer) was used after radical surgery. In patients of the chemotherapy group with one to three lymph nodes involved in the axilla, the five-year cancer-free survival rate was 84.8% compared with 57.3% in the control group (P < 0.05), and the five-year cumulative recurrence in distant sites was 5.1% compared with 31.1% in the control (P < 0.05). The effectiveness of chemotherapy was much less marked in patients without nodal metastasis and with four or more nodes involved. Histologically, scirrhous cancer was the type that responded most favorably to chemotherapy, even in patients without axillary involvement. Premenopausal patients benefited more than postmenopausal patients from chemotherapy. A combination of mitomycin C and cyclophosphamide was more effective than their use singly. The present chemotherapy regimen was effective primarily in moderately advanced stages of breast cancer with decreased incidence of distant metastasis. PMID- 6254631 TI - Effect of dietary fiber on intestinal bacterial beta-glucuronidase activity in chicks fed a cholesterol-containing diet. AB - The effect of dietary fiber isolated from blackgram (Phaseolus mungo) was studied on the metabolic activity of microflora in the large intestine and cecum in chicks fed a cholesterol diet. The results indicate that inclusion of cholesterol in the diet increased the bacterial as well as tissue (large intestine, small intestine, and cecum) beta-glucuronidase activity when compared to a cholesterol free diet. Dietary fiber isolated from blackgram when given at 30% level to chicks fed a cholesterol diet significantly lowered bacterial as well as tissue beta-glucuronidase activity. Pure cellulose at the same level did not have this effect. PMID- 6254632 TI - Apocrine differentiation in human mammary carcinoma. AB - Six invasive carcinomas that contained apocrine differentiation as the primary morphologic pattern were selected from a series of 1500 prospectively examined breast carcinomas (0.4%). While apocrine features were seen in many breast tumors, these six cases were identified by uniformly fine granular, pale, eosinophilic cytoplasm with apical cytoplasmic projections similar to that seen in apocrine metaplasia. In each example, ultrastructural analysis revealed the presence of numerous 400-600 nm membrane bound vesicles with dense homogeneous osmophilic cores. These granules clustered toward the apex of the cytoplasm in the majority of the epithelial cells. All six tumors were deficient in high affinity, low-capacity 8S estrogen and progesterone proteins, while a high capacity, low-affinity, nonsaturable 4S progesterone-estrogen binding protein was observed. Cortisol did not bind to this protein. These observations characterize the ultrastructure of apocrine carcinoma as a variant of human mammary carcinoma. PMID- 6254633 TI - Esters of phosphonopropionic and phosphonoacetic acids: effect on synthesis of Epstein-Barr virus (EBV) antigens and on transformation of cord blood lymphocytes by EBV. AB - Cell cytotoxicity, inhibition of synthesis of Epstein-Barr virus (EBV) viral capsid antigen (VCA), nuclear antigen (EBNA) and transformation of human cord blood lymphocytes (CBL) by EBV, were studied using the disodium salt of phosphonoacetic acid (PAA), ethyl diethyl-phosphonoacetate (Et-PAA) and two derivatives of phosphonopropionic acid: ethyl diethyl-2-phosphonopropionate (Et-2 PPA) and ethyl diethyl-3-phosphonopropionate (Et-3-PPA). These substances were tested on EBV producing cell lines, B.95-8 and P3HR1. VCA and EBNA synthesis were determined by immunofluorescence and transformation of CBL by 3H-thymidine uptake. Up to 100 micrograms/ml of PAA were not toxic to 2.10(5) cells. Et-PAA, Et-2-PPA and Et-3-PPA were nontoxic at concentrations up to 2000 micrograms/ml. PAA inhibited 82.05% of EBV VCA synthesis at a concentration of 50 micrograms/ml. Et-PAA inhibited 47.01% of VCA at a concentration of 100 micrograms/ml and 78.09% at a concentration of 2000 micrograms/ml. Et-2-PPA inhibited 41.04% of VCA at 100 micrograms/ml and 80.87% when used at 2000 micrograms/ml. Et-3-PPA inhibited 35.06% of VCA at 100 micrograms/ml and 69.92% at 2000 micrograms/ml. Removal of the substances restored VCA synthesis. EBNA synthesis was not affected by these substances. PAA completely inhibited the transformation of human CBL by EBV at a concentration of 100 micrograms/ml. Et-PAA at a concentration of 2000 micrograms/ml completely inhibited 3H-thymidine uptake. ET-2-PPA was less effective whereas Et-3-PPA had almost no effects at the same concentration. PMID- 6254634 TI - Properties of uridine-cytidine kinase derived from L1210 leukemia cells. AB - Uridine-cytidine kinase isolated from murine L1210 leukemia cells exist in several isozymic forms, as indicted by isoelectric focusing and by column chromatography on Sepharose 6B. Of 39 compounds thus far examined as potential inhibitors of the phosphorylation of uridine by ATP, four were of significant activity: 5'-azido-5'-deoxycytidine, 5'-O-nitro-5-fluorouridine, 5'-O nitrouridine, and 5'-azido-5'-deoxyuridine. 5'-Azido-5'-deoxycytidine was the most active (competitive with uridine) and exhibited a Ki of 37 x 10(-5) M. Other properties of uridine-cytidine kinase were examined, and the apparent Michaelis constants for uridine, cytidine, and adenosine 5'-triphosphate were 23 x 10(-5) M, 15 x 10(-5) M, and 34.9 x 10(-5) M, respectively. PMID- 6254635 TI - Spontaneous adrenal tumors in the aged, ovariectomized NIH swiss mouse without enhanced retrovirus expression. AB - A high incidence of adrenal tumors was observed in aged female NIH Swiss mice which had been ovariectomized at 2 to 4 weeks of age but not in nonovariectomized controls. Although tumors weighing more than 1 g were not infrequent in the oldest (> 24 months) animals, adrenal glands did not appear macroscopically abnormal before the age of 18 months. Histologically, however, focal or diffuse abnormalities were found in essentially every gland examined from mice over 12 months of age, including glands of normal size. Since the NIH Swiss mouse has been shown to contain an endogenous xenotropic virus whose expression is under hormonal control, the adrenal tumors were examined in detail for evidence of abnormal viral expression. We were unable, by a variety of techniques, to demonstrate elevated expression of type C virus in these adrenal tumors. PMID- 6254636 TI - Metabolism and chemotherapeutic activity of 9-beta-D-arabinofuranosyl-2 fluoroadenine against murine leukemia L1210 and evidence for its phosphorylation by deoxycytidine kinase. AB - The 2-fluoro derivative of 9-beta-D-arabinofuranosyladenine (2-F-ara-A) and its soluble 5'-formate and 5'-phosphate derivatives were therapeutically effective against the parent leukemia L1210 (L1210/0). 2-F-ara-A and 9-beta-D arabinofuranosyladenine 5'-formate were inactive aginst a 1-beta-D arabinofuranosylcytosine-resistant subline (L1210/ara-C) that was deficient in deoxycytidine kinase. Deoxycytidine prevented 2-F-ara-A-induced inhibition of proliferation of L1210/0 cells in culture and alleviated 2-F-ara-a inhibition of DNA synthesis. After treatment of mice with 9-beta-D-arabinofuranosyladenine 5' formate, intracellular levels of the 5'-triphosphate of 9-beta-D arabinofuranosylfluoroadenine in leukemia cells were more than 10 times higher in L1210/0 cells than in L1210/ara-C cells. Similar results were obtained in this line of leukemia cells from mice treated with the 5'-monophosphate of 9-beta-D arabinofuranosyl-2-fluoroadenine. Thus, L1210/ara-C cells deficient in deoxycytidine kinase activity were also deficient in capacity to phosphorylate 2 F-ara-A. Kinase activity from L1210/0 cells for deoxycytidine and for 2-F-ara-A coeluted from calcium phosphate cellulose and from diethylaminoethyl cellulose columns and had similar mobility on gel electrophoresis. Deoxyadenosine kinase was clearly separated from deoxycytidine kinase. Deoxycytidine competed with 2-F ara-A for phosphorylation by the partially purified enzyme from L1210 cells. These results indicate that 2-F-ara-A is phosphorylated to the 5'-monophosphate by deoxycytidine kinase of leukemia L1210 cells. PMID- 6254637 TI - Humoral immune reactivity to feline leukemia virus and associated antigens in cats naturally infected with feline leukemia virus. PMID- 6254638 TI - Superoxide dismutase and superoxide radical in Morris hepatomas. AB - Total superoxide dismutase (SOD) and manganese superoxide dismutase (Mn SOD) specific activities were measured in tissue homogenates and in isolated mitochondria from normal rat liver and three Morris hepatomas of different growth rates. Total SOD and Mn SOD specific activities were decreased in all tumor homogenates when compared to normal liver; the lowest activity was associated with the fastest growing tumor. These results are consistent with the hypothesis that total Mn SOD specific activity is decreased in all tumors. The Mn SOD specific activity was similar to the total SOD specific activity of isolated mitochondria, indicating that mitochondrial SOD is almost entirely manganese containing. This activity was decreased in the fast- and medium-growth-rate hepatomas but was slightly increased in the tumor with the slowest growth rate when compared to liver. The normal or higher than normal mitochondrial Mn SOD specific activity indicates that decreased mitochondrial SOD specific activity is not a characteristic of all tumors. Superoxide radical (O2-.) formation was measured in submitochondrial particles obtained by sonication of isolated mitochondria and subsequent washings to remove the SOD. The difficulty encountered in reducing the SOD activity suggests that at least part of the mitochondrial SOD might be associated with the mitochondrial membrane. In liver submitochondrial particles, O2-. was formed only when succinate and antimycin A were used together, as substrate and inhibitor of the electron transport chain, respectively. In the hepatomas studied for O2-. production (slow- and fast-growth rates), the formation of the radical was detected in the presence of succinate even when no inhibitor was present. Antimycin A stimulated the production of O2-. in normal rat liver and slow-growth-rate tumor, but not in fast-growth-rate tumor submitochondrial particles. Reduced nicotinamide adenine dinucleotide did not lead to the production of O2-. by normal liver or hepatoma submitochondrial particles. Mitochondrial membrane damage was seen in micrographs of the medium- and fast-growing hepatomas. This could be a consequence of low mitochondrial SOD concomitant with a flux of superoxide, if the radical is produced in vivo by these mitochondria. PMID- 6254639 TI - Phase I study of 1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidyl)-1-nitrosourea (NSC 95466) in adults with solid tumors. PMID- 6254640 TI - Multiple hormone receptors in the adenylate cyclase of human adrenocortical tumors. AB - Adenylate cyclase responses to pituitary hormones including adrenocorticotropic hormone (ACTH), biogenetic amines, prostaglandin E1 (PGE1), angiotensin II, and glucagon were evaluated in adrenocortical tumors and hyperplastic adrenal tissues, obtained from patients with Cushing's syndrome at surgery, and in normal adrenals. The adenylate cyclase of two normal adrenals was activated only by ACTH and PGE1 among the hormones tested, while that of two hyperplastic adrenal tissues due to excessive pituitary ACTH secretion was stimulated only by ACTH. Of five ACTH-responsive adrenocortical adenomas, in contrast, three were stimulated by norepinephrine, two by epinephrine, one by thyroid-stimulating hormone, and one by luteinizing hormone in addition to ACTH, indicating the presence of multiple receptors for hormones other than ACTH and PGE1 in these four tumors. The cyclase of an ACTH-unresponsive adrenocortical carcinoma ws activated only by PGE1 and not by other hormones including ACTH, whereas that of an ACTH-responsive adrenocortical nodular hyperplasia was stimulated by ACTH and glucagon but not by other hormones including PGE1. These results indicate the presence of multiple receptors for hormones other than ACTH and PGE1, the normal adrenocortical stimulants, in human adrenocortical tumors, particularly in adrenal adenomas, but not in normal and hyperplastic (of whichever an etiology) adrenocortical tissues, suggesting a functional alteration of the cellular membrane receptors in human adrenocortical tumors. PMID- 6254642 TI - In vivo potentiation of concanavalin A-bound L1210 vaccine by antimacrophage agents. AB - Carrageenan potentiated in vivo the primary and secondary responses by concanavalin A (Con A)-bound L1210 murine leukemia vaccine and induced in histocompatible animals enhanced immune resistance to subsequent inoculations of live L1210 cells. This enhancement was critically dependent on the vaccine preparation and the administration timing of carrageenan. Carrageenan potentiated Con A-free vaccine to a much lesser extent if at all, than did Con A-bound vaccine, and it was effective only on the day of or one day after vaccine administration. This enhancement was L1210 specific as evidenced by the lethal growth of P388 leukemia cells in animals inoculated with Con A-bound L1210 vaccine and carrageenan. This is explicable by the increase of spleen but not peritoneal exudate effector cells as measured by suppression of in vitro L1210 cell growth. The following findings suggested that potentiation of Con A-bound vaccine by carrageenan was achieved by affecting suppressor macrophages. Silica and trypan blue, other antimacrophage agents, potentiated Con A-bound vaccine. The enhancement was nullified by the macrophage-stabilizing agent, poly-2 vinylpyridine N-oxide. This hypothesis was further evidenced by the following findings. Phagocytic peritoneal cells induced by Con A-bound vaccine and adhering to the plastic vessel suppressed in vitro spleen cell blastogenesis. Antimacrophage agents abrogated not only production but also activity of these suppressor cells. The combined administration of Con A-bound L1210 vaccine and carrageenan produced an enhanced antitumor immune response and prolonged the life span of tumor-bearing animals marginally but significantly. PMID- 6254644 TI - Growth of human small cell (oat cell) carcinoma of the lung in serum-free growth factor-supplemented medium. PMID- 6254645 TI - Multinucleation in the presence of cytochalasin B by RNA tumor virus-transformed cells. AB - RNA tumor virus-transformed cell cultures derived from rat, mouse, hamster, and mink were examined for their response to cytochalasin B (CB), and the expression of this marker was correlated with growth in soft agar and tumorigenicity in vivo. Continuous cell lines transformed and chronically infected with Moloney murine sarcoma-leukemia virus (M-MSV-MuLV) or Kirsten murine sarcoma-leukemia virus were extensively multinucleated when treated with CB. Similarly, nonproducer Moloney murine sarcoma virus- or Rous sarcoma virus-transformed cells multinucleated in response to CB treatment, whereas uninfected or murine leukemia virus-infected cells remained predominately binucleate under comparable conditions. Rat kidney or embryo cell cultures, one to two passages after infection with M-MSV-MuLV, were highly multinucleated following CB treatment and acquired the ability to grow in soft agar. Mouse 3T3 cell lines, newly infected with M-MSV-MuLV, exhibited a moderate degree of CB-induced multinucleation. CB induced multinucleation was directly correlated with anchorage-independent growth for most of the cell lines tested. An exception was the Moloney murine sarcoma virus-transformed mink cells which multinucleated in response to CB treatment but were unable to proliferate in soft agar. CB-induced multinucleation was directly correlated with the tumorigenicity of M-MSV-MuLV-transformed rat cells in syngeneic animals. These results demonstrate that CB-induced multinucleation is a useful in vitro growth-related marker of cell transformation by RNA tumor viruses and, in addition, show that this parameter of cell transformation is closely correlated with anchorage-independent growth in vitro and tumorigenicity in vivo. PMID- 6254646 TI - Carcinoembryonic antigen for monitoring patients with small cell carcinoma of the lung during treatment. AB - Carcinoembryonic antigen (CEA) was measured at specific intervals in the plasma of 56 patients with small cell carcinoma of the lung. Of these patients, 47 had serial analyses for varying periods during their illness, 42 had pretreatment CEA levels, and 17 of the latter patients had determinations throughout the entire course of their disease. Pretreatment CEA levels were elevated above 2.5 ng/ml for 74% of the 42 patients and above 5.0 ng/ml for 48%. Although exceptions were noted, in general, a direct relationship was found between pretreatment CEA levels and extent of disease or tumor burden. Initial stage of disease, however, was more predictive of survival than was the pretreatment CEA level. With response to therapy, a corresponding decrease in CEA levels occurred for patients with an elevated pretreatment level. For those patients with a pretreatment CEA level below 5.0 ng/ml, an immediate slight increase in level was often seen associated with response and followed by a subsequent fall after one month. A rising CEA level was usually found with recurrence or progression of disease after initial response and occurred frequently prior to clinical evidence of progression. In combination with careful clinical evaluation, serial CEA measurements can aid in assessing tumor changes associated with treatment in patients with small cell carcinoma of the lung particularly at the times of recurrence or disease progression following a partial or complete response. PMID- 6254641 TI - Insulinotropic effect of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate in rat pancreatic islets. AB - In isolated rat pancreatic islets, the tumor-promoting agent 12-O tetradecanoylphorbol-13-acetate (TPA), when used in the 2.10(-9) to 2.10(-7) M range, was found to stimulate insulin release both in the absence and presence of glucose. The non-tumor-promoting agent 4-methylphorbol-12,13-didecanoate failed to stimulate insulin release. The insulinotropic capacity of TPA was enhanced by glucose in a dose-related fashion. In the absence of glucose, the TPA-stimulated release of insulin was a slowly induced and not rapidly reversible phenomenon. It was inhibited by antimycin A, by epinephrine, at low temperatures, and in the absence of extracellular Ca2+ or the presence of cytochalasin B, was unaffected by the organic calcium antagonist D600 or indomethacin, and was potentiated by theophylline. No obvious effect of TPA upon 86Rb or 32P efflux and 45Ca net uptake could be detected in the isolated islets. However, TPA caused a progressive increase in both 45Ca fractional outflow rate and cyclic adenosine 3':5'-monophosphate content in the islets. It is proposed that the insulinotropic action of TPA may be due, in part at least, to interference with the transport of calcium by native ionophores. PMID- 6254643 TI - Cytotoxic activities of monoclonal antibodies against the envelope proteins of murine leukemia virus. AB - Monoclonal antibodies against the envelope proteins [gp70 and p15(E)] of murine leukemia virus react with the cell surface of virus-infected cells. The specificity and potency of these antibodies exceed those observed with conventional polyvalent antisera. In cytotoxic assays, certain of the monoclonal anti-gp70 antibodies demonstrate 1000-fold differences in their titer on leukemic and normal thymus cells. PMID- 6254647 TI - Stimulation of synthesis and secretion of chorionic gonadotropin subunits by eutopic and ectopic hormone-producing human cell lines. AB - The effects of dibutyryl cyclic adenosine 3'3':-5'-monophosphate (AMP) and sodium butyrate on the synthesis and secretion of human chorionic gonadotropin (HCG) by trophoblastic and nontrophoblastic human cell lines were studied by radioimmunoassay and pulse-chase labeling techniques. Dibutyryl cyclic AMP stimulated synthesis and secretion of HCG-alpha and HCG-beta subunits by the trophoblastic cell lines JAR and BeWo, whereas butyrate had no effect or decreased secretion. On the other hand, a number of nontrophoblastic cell lines (including the breast carcinoma lines ZR-75-31, BT-20, and MCF-7; the bronchogenic carcinoma line ChaGo; and the cervical carcinoma line HeLa S3) were induced to synthesize and secrete increased amounts of HCG subunits by butyrate, but dibutyryl cyclic AMP had less or no stimulatory effect. The nontrophoblastic brain tumor line CBT was an exception to this general rule in that HCG-beta production was stimulated by dibutyryl cyclic AMP but not by butyrate. In all cases, the drug-induced increase in HCG subunit secretion was directly proportional to the elevation of HCG subunit synthesis. These data suggest that the differential effects of dibutyryl cyclic AMP and butyrate on trophoblastic and nontrophoblastic cells reflect differences in the transcription or translation of HCG subunit genes induced by these agents in the two cell types. PMID- 6254648 TI - Effect of ovariectomy on hormone receptors and growth of N-nitrosomethylurea induced mammary tumors in the rat. AB - Estrogen receptor(s) (ER), progesterone receptor(s) (PGR), androgen receptor(s) (ANR), and prolactin receptor(s) (PRLR) were measured in N-nitrosomethylurea induced mammary tumors in intact female Sprague-Dawley rats and in rats 9 days after ovariectomy. Following ovariectomy, 12 of 15 tumors regressed to 47.7 +/- 5.5% of the original size (hormone-dependent tumors), while the remaining three had arrest of growth reaching 88.8 +/- 7.3% of their original sizes. Cytosol ER level was 50.3 +/- 6.6 fmol/mg protein in tumors of intact rats and was significantly lower (25.6 +/- 8.3 fmol/mg, p < 0.025) in the ovariectomized group. PGR was abundantly present in ten of 13 tumors of intact rats (mean, 144.5 +/- 46.8) but was undetectable in five of six hormone-dependent tumors after ovariectomy (p < 0.01). ANR ws detectable at low levels in only four of 13 tumors of intact rats but in none of six hormone-dependent tumors after ovariectomy. PRLR was not significantly different in tumors of intact and ovariectomized rats (20.6 +/- 2.4 and 15.6 +/- 1.8 fmol/mg, respectively). In three tumors that had arrest of growth after ovariectomy, the levels of ER, PGR, ANR, and PRLR were not significantly different from those of the hormone-dependent tumors. We conclude that the majority of N-nitrosomethylurea-induced rat mammary tumors are hormone dependent. ER, PGR, and PRLR were abundantly present in the majority of these tumors, while ANR was present in only four of 13 tumors. The levels of ER and PGR were significantly lower following ovariectomy, while PRLR was not significantly changed. PMID- 6254649 TI - Reaction patterns of herpes simplex virus type 1 and type 2 proteins with sera of patients with uterine cervical carcinoma and matched controls. AB - Serum from 105 individuals with diagnosed uterine cervical cancer and 231 matched controls were examined for their ability to react with a large number of herpes simplex virus type 1 or type 2 (HSV-1, HSV-2) proteins. Radiolabeled HSV-1 or HSV 2 proteins were mixed with test serum and immune complexes were isolated with staphylococcal protein A. Viral proteins in the immune complexes were resolved by polyacrylamide gel electrophoresis and visualized by fluorography. When the frequency of precipitation for cancer and control serum was calculated for each HSV-1 and HSV-2 protein, the results demonstrated that four HSV-1 and 11 HSV-2 proteins were precipitated more frequently by cases than by controls (p less than or equal to 0.05). However, since these results could be influenced by the presence or absence of HSV-2 specific antibodies as well as social, economic, and sexual history, the data were grouped and analyzed according to these parameters. This enabled all significant differences between case and control sera in the precipitation of HSV-1 or HSV-2 proteins to be abolished except for two HSV-2 proteins with molecular weights of 38,000 and 118,000. These two proteins appear to be tumor associated and not merely covariables of past infection or risk factors alone. PMID- 6254650 TI - Factors affecting the expression of carcinoembryonic antigen at the surface of cultured human colon carcinoma cells. AB - Factors affecting the expression of carcinoembryonic antigen (CEA) at the surface of in vitro human colon carcinoma cells were determined using 125I-labeled antibodies. Binding of specific anti-CEA antibodies resulted in polar redistribution of CEA, followed by endocytosis of most of the CEA-anti-CEA complexes. These processes were temperature and energy dependent. CEA removed from the tumor cell surface by antibody was totally replaced within 6 hr at 37 degrees, and the reexpression of CEA required protein synthesis. Examination of clonally derived subpopulations of various strains of human colon cancer cells indicated that control over the level of cell surface CEA expressed was genetically stable in vitro. CEA expression was enhanced in a low-CEA-producing strain by incorporating theophylline in the culture medium, and the inclusions of bromodeoxyuridine enhanced the expression of a high-CEA-producing strain. The kinetics of enhancement of CEA expression by these two drugs differed. These findings suggest that CEA expression may be controlled by more than a single gene function. PMID- 6254651 TI - Calcitonin and 1,25-dihydroxyvitamin D3 receptors in human breast cancer cell lines. AB - Five human breast cancer cell lines (MCF 7, T 47D, BT 20, MDA 157, and MDA 231) and a human breast epithelial cell line (HBL 100) have been found to contain specific high-affinity receptors for 1,25-dihydroxyvitamin D3, Kd values ranged from 0.6 to 2.0 X 10(-11) M and receptor concentration from 31 to 150 fmol/mg cytosol protein. Two of the breast cancer lines (MCF 7 and T 47D) contain specific high-affinity receptors for calcitonin and a calcitonin-responsive adenylate cyclase, which have been characterized with the aid of salmon, eel, and human calcitonins and in several substituted analogues of human calcitonin. The 1,25-dihydroxyvitamin D3 receptor may reflect a normal property of the breast cell. Breast cancer cell lines provide a useful source of 1,25-dihydroxyvitamin D3 receptors. Their coexistence with a calcitonin receptor and biological response in some breast cancers offers the opportunity to investigate new aspects of breast cancer endocrinology. PMID- 6254652 TI - Epstein-Barr virus-transformed human lymphoblastoid cells for study of sister chromatid exchange and their evaluation as a test system. AB - Epstein-Barr virus-transformed human lymphoblastoid cell lines are suitable for detection of sister chromatid exchange (SCE) induced by mutagens-carcinogens because they have shown a stable chromosome number and stable frequency of spontaneous SCE for more than two years in culture. Their spontaneous and induced SCE frequencies were practically the same as those of phytohemagglutinin stimulated lymphocytes from the same blood donors. The SCE responses of one established cell line, NL3, to 13 typical mutagens and five nonmutagens were examined. This cell line responded to all the mutagens tested but not to the nonmutagens. The SCE-inducing activities of these chemicals were well correlated with their mutagenic activities assayed with the Salmonella system by Ames' and Sugimura's groups, although there were a few but significant deviations. PMID- 6254654 TI - Cyclic AMP and mammary tumor regression. PMID- 6254653 TI - Superoxide assay-leukocyte adherence inhibition test and a soluble factor which stimulates the adherence of macrophages. AB - A modified method for the leukocyte adherence inhibition test is described. Peritoneal cells from immune guinea pigs or peripheral mononuclear cells from cancer patients were incubated with immunizing antigen or tumor extract in a 4-mm wide glass microcell for spectrophotometer analysis. Instead of visual cell counting, the cells adherent to the bottom of the microcell were stimulated with cytochalasin E and wheat germ agglutinin, and the amount of the superoxide (O2.-) generated from the adherent macrophages or monocytes was assayed. Antigen specific adherence inhibition of peritoneal cells of the immunized guinea pigs was detected 2 weeks after immunization. In contrast, cell adherence was stimulated after 3 weeks. It was shown that a soluble factor was responsible for the adherence stimulation and that nonadherent cells were necessary for its production. Peripheral mononuclear cells of 70% of the tumor-bearing lung cancer patients reacted to the lung tumor extract (9 adherence inhibitions and 7 adherence stimulations per 23 patients). Twenty-five % (3 of 12) of tumor-free patients showed positive reactions, all with adherence stimulation. Of the 12 healthy donors, 3 cases of pneumonia, one case of angiosarcoma of the left flank, one case of hemangiopericytoma of the mediastinum, and 8 cases of breast cancer, non reacted with the lung tumor extract, and only one of 7 lung tuberculosis patients showed positive adherence stimulation. PMID- 6254655 TI - Morphological alterations and transmembrane potential of cultured glia cells. PMID- 6254656 TI - The separation of extra- and intracellular cholinesterases of the rat superior cervical ganglion by mild proteolytic treatment. A quantitative, histochemical and electron microscope cytochemical study. PMID- 6254657 TI - [Antibody against hepatitis A virus--radioimmunological proof in convalescents and in immunoglobulins (author's transl)]. PMID- 6254658 TI - Ultrahistochemical and autoradiographic evidence of epithelial transport in the uterus of the ovoviviparous salamander, Salamandra salamandra (L.) (Amphibia, Urodela). AB - The uterine epithelium of pregnant females of the terrestrial ovoviviparous Salamandra salamandra is characterized by a considerable enlargement of its basolateral surface. Chloride and cations (among others sodium), preferentially within the intercellular spaces, can be demonstrated ultrahistochemically. There is indirect evidence of Na+ --K+ -ATPase activity along the basolateral plasma membranes of the epithelial cells using the Sr-technique for demonstration of a K+ -NPPase and 3H-ouabain autoradiography. Preliminary measurements reveal a potential difference across the uterine wall of 15--25 mV, the lumenal (mucosal) surface being negative with respect to the coelomic (serosal) surface, and a short circuit current of 200--300 microA. The possible electrogenic ion transport is ouabain-sensitive. The results are in agreement with the model of a "forward" transporting, i.e. absorptive epithelium. An active transport of solute out of the uterine lumen across the epithelium to the subjacent connective tissue and the blood vessels may be involved in the regulation of an intrauterine milieu appropriate for the development of the offspring. PMID- 6254659 TI - Localization of Na+, K+ -ATPase to the inside of the basolateral cell membranes of epithelial cells of proximal and distal tubules in rabbit kidney. AB - Cysteine-sensitive alkaline phosphatase and/or ouabain-sensitive Na+, K+ -ATPase were studied by ultrastructure cytochemistry in epithelial cells of proximal and distal kidney tubules. Alkaline phosphatase reactivity was confined to the surface of the microvillous luminal cell membrane of proximal tubule cells, whereas distal tubules and collecting ducts were unreactive. The Na+, K+- ATPase reactivity was localized evenly along the cytoplasmic side of the basolateral cell membrane of cells of proximal and distal tubules and in collecting ducts. In the proximal tubules, where the activity was strongest, the Na+, K+- ATPase deposits were also found in the 10--50 nm gap between the cell membrane and the cisternae of tubulo-cisternal endoplasmic reticulum (TER) underlying a major part of the basolateral cell membrane. The restriction of NA+, K+ -ATPase sites, which are involved in extrusion of Na+ from the cell, to a narrow cytoplasmic compartment located between the cell membrane and the cisternae of TER, is consistent with a transport role for the TER. PMID- 6254660 TI - Functional reinnervation of the neostriatum in the adult rat by use of intraparenchymal grafting of dissociated cell suspensions from the substantia nigra. PMID- 6254661 TI - Origin of retroviruses from cellular moveable genetic elements. PMID- 6254662 TI - Cellular location of viral transforming proteins. PMID- 6254663 TI - The primary structure of the human epsilon-globin gene. AB - We describe the complete nucleotide sequence of the human epsilon-globin gene including 387 nucleotides of 5' flanking sequence and 301 nucleotides of 3' flanking sequence. The arrangement of coding, noncoding and intervening sequences in this gene is entirely consistent with its identification as the embryonic beta like globin gene. PMID- 6254664 TI - The nucleotide sequence of the human beta-globin gene. AB - We report the complete nucleotide sequence of the human beta-globin gene. The purpose of this study is to obtain information necessary to study the evolutionary relationships between members of the human beta-like globin gene family and to provide the basis for comparing normal beta-globin genes with those obtained from the DNA of individuals with genetic defects in hemoglobin expression. PMID- 6254665 TI - A mouse globin gene promoter is functional in SV40. AB - We have constructed two SV40 recombinants carrying a complete mouse alpha-globin gene with its presumptive promoter region. In one recombinant the globin gene can be transcribed either from its own promoter or from the adjacent viral late region promoter. In the other efficient globin expression should depend only upon the promoter carried by the chromosomal globin gene. We show that both viruses direct the synthesis of functional globin mRNA in infected monkey kidney cells and that this mRNA has a 5' terminus indistinguishable from that of authentic globin mRNA. These results suggest that the cloned globin gene contains a functional promoter that is accurately recognized in monkey kidney cells. PMID- 6254666 TI - Loss of reiterated DNA sequences during serial passage of human diploid fibroblasts. AB - A specific family of tandemly repeated DNA sequences was found to diminish in the human genome after serial passage of three strains of diploid fibroblasts. Eco RI restriction fragments of 340 and 680 bp were significantly reduced in quantity at late passage as determined by autoradiography of 14C-DNA and also by ethidium bromide fluorescence. The reduction in these closely related DNA sequences was confirmed by saturation hybridization to excess 14H-RNA transcribed from a homogeneous restriction fragment recleaved from the 340 bp DNA. The maximal fraction of DNA hybridizing to the 3H-RNA probe declined by 33-50% over 21-41 population doublings. Divergence and/or methylation of such sequences could not account for these results since the thermal stability of cRNA:DNA duplexes actually increased by 0.3 degrees C at late passage. Total highly repetitive sequences assayed by reassociation kinetics were also substantially reduced at late passage, implying that depletion may be common to many repeat families in DNA. The denaturation temperature for such rapidly reassociated duplexes again increased slightly at late passage, possibly reflecting the minor decreases in DNA methylation which were detected in two of the cell strains. Karyotype analyses demonstrated that over 95% euploidy was maintained, with no specific chromosome loss and no visible deletions at late passage. The depletion of reiterated sequences during repeated cell division is thus attributed to numerous small DNA deletions, which may arise from unequal recombination coupled with selection or from a nonreciprocal mechanism such as excision. PMID- 6254667 TI - Regulated replication of DNA microinjected into eggs of Xenopus laevis. AB - Purified circular DNA of SV40 or polyoma virus has been injected into unfertilized eggs of Xenopus laevis. Injected DNA initiates and completes multiple rounds of semiconservative replication while observing cellular regulatory signals. Thus replication initiation of double-stranded templates is induced after the oocyte is matured in vitro by progesterone. Only one round of replication of injected DNA is observed in a single cell cycle. When protein synthesis is inhibited unreplicated molecules continue to initiate replication at an undiminished rate, but reinitiation on previously replicated molecules is completely and selectively abolished. The DNA sequence requirements for the replication of injected DNA have been investigated. A variety of procaryotic DNA molecules and circularized fragments of SV40 or polyoma DNA replicate, regardless of whether they contain the viral origin of DNA replication. These results suggest that a specialized DNA sequence is not essential for the initiation of semiconservative DNA replication in the Xenopus embryo, nor is a specialized sequence essential for the mechanism which prevents reinitiation on a molecule which has already replicated within a cell cycle. The possibility is discussed that viral origins of replication are not valid models for the eucaryotic chromosome but are adaptations for uncoupling viral replication from the mechanism which prevents reinitiation within a cell cycle. PMID- 6254668 TI - Torsional tension in the DNA double helix measured with trimethylpsoralen in living E. coli cells: analogous measurements in insect and human cells. AB - The rate of covalent photobinding of trimethylpsoralen to DNA is greater when the DNA is wound with negative superhelical tension than when it is relaxed. In vitro the rate of photobinding is directly proportional to the negative superhelical density of the DNA. Thus measurement of the rate of photobinding provides an assay for probing in vivo unrestrained tension in the winding of the DNA double helix. This approach has been applied to measure torsional tension in DNA as it is packaged in living E. coli. Drosophila and HeLa cells. A method is described for measuring the rate of photobinding to intracellular DNA and rRNA, and for using the latter measurement as an internal control of the rate of me3-psoralen photobinding in vivo. This permits more accurate and reproducible measurement of changes in the DNA-psoralen photobinding reaction. The me3-psoralen probe interacts with intracellular bacterial DNA as expected for a purified DNA duplex wound with superhelical density sigma = -0.05 +/- 0.01. This superhelical tension is relaxed in cells when multiple single-strand breaks are introduced into the chromosomal DNA by gamma-irradiation. Similar relaxation occurs when cells are treated with the DNA gyrase inhibitor coumermycin. The results suggest that the DNA double helix is wound with torsional tension in vivo and that DNA supercoils which are equilibrated with this tension are not completely restrained in nucleosome-like structures. Torsional tension in the DNA of eucaryotic cells is not detectable in analogous measurements of the packaged DNA of HeLa and Drosophila cells. The simplest interpretation of this finding is that, within the limits of detection, all superhelical turns in the DNA are restrained in nucleosomes or nucleosome-like structures in these eucaryotic cells. PMID- 6254669 TI - Identification of a cellular protein substrate phosphorylated by the avian sarcoma virus-transforming gene product. AB - The avian sarcoma virus-transforming gene product (pp60src) appears potentially able to mediate cell transformation via phosphorylation since it is tightly associated with a protein kinase activity. We have searched for and have been able to identify a normal cellular protein that appears to be a substrate of pp60src. The phosphorylation of this protein (34K) in transformation-specific in ASV-transformed cells of both avian and mammalian origin. Moreover, the 34K polypeptide serves as a substrate for the pp60src phosphotransferase activity in vitro and is phosphorylated at a site identical to the major site of phosphorylation in vivo. These data suggest that upon transformation the 34,000 dalton protein is phosphorylated directly as a result of pp60src activity. PMID- 6254671 TI - Genetic and nongenetic factors in expression of infectious murine leukemia viruses in mice of the DBA/2 x RF cross. PMID- 6254670 TI - A unique glycoprotein containing GR-mouse mammary tumor virus peptides and additional peptides unrelated to viral structural proteins. AB - A glycoprotein of molecular weight 130,000 (gP130) has been precipitated from the cytoplasm of GR-strain mouse mammary tumor (GR-MMT) cells by a rabbit antiserum (anti-MMTV) to GR-strain mouse mammary tumor virus (GR-MMTV). This protein was not precipitated by antisera specific for detergent-disrupted C3H-strain MMTV (C3H-MMTV); C3H-MMTV glycoproteins; C3H-MMTV nonglycosylated proteins; GR-MMTV p25 or p12; RIII strain (milk) MMTV proteins; or Rauscher murine leukemia virus (R-MuLV) proteins; nor was it precipitated by normal rabbit serum. Two dimensional thin layer analysis of 35S-methionine-containing tryptic peptides revealed that five of nine gp33 peptides and one of seven gp55 peptides are shared by gP130 and gPr76env. The envelope protein precursor, gPr76env, contains all of the gp33 peptides and six of seven gp55 peptides. One peptide in gPr76env, possibly a gp55-gp33 junction peptide, is also apparently present in gP130. Six of ten p25 peptides and four more gag-related peptides are shared by PR78gag and gP130. Protein gP130 also contains several tryptic peptides not found in gPr76env or in the core protein precursors Pr78gag, Pr110gag or Pr180gag-pol. Radioimmunoprecipitation experiments showed that gP130 could be precipitated from extracts of GR-MMTV cells with anti-MMTV serum even after antibodies to the known MMTV structural proteins had been removed from the serum by absorption. Both gP130 and a second protein, p30, were found in immunoprecipitates of detergent disrupted isotopically labeled GR-MMTV treated with the absorbed anti-MMTV serum. These results suggest that antibodies to gP130 in the anti-MMTV serum are capable of recognizing those protein sequences unique to gP130; that is, those protein sequences which are not related to viral structural proteins. In light of these data and data published previously, gP130 is apparently a polyprotein containing juxtaposed components translated from the 5' and 3' end of the MMTV genome and protein components not previously identified as virus-specific. PMID- 6254672 TI - Clonal variants of PC12 pheochromocytoma cells with altered response to nerve growth factor. AB - We describe the isolation and characterization of clonal variants of PC12 pheochromocytoma cells which have been selected for loss of response to nerve growth factor (NGF). PC12 cells mutagenized with ethyl methanesulfonate were cultured in the presence of NGF, causing normal cells to cease proliferation and allowing the isolation of cell clones which do not show growth inhibition by NGF. Some but not all of these clones also failed to respond morphologically to NGF. Forty clones were isolated and characterized. Many exhibited altered morphologies of a variety of types, including clones with an NGF-independent formation of neurites and clones with various types of flattened epithelial morphology. Variant clones appeared to be mutants since their frequency of occurrence was increased by mutagen, the clones were generally phenotypically stable and no alteration in chromosomal composition was observed. Three clones lacked NGF receptor. Some clones responded morphologically to NGF (by forming neurites) without inhibition of proliferation. Several clones which did not otherwise respond to NGF nevertheless responded with transient membrane ruffling. Thus transient changes in cell surface morphology caused by NGF binding do not necessarily lead to subsequent responses. Several alternative hypotheses concerning the nature of the mutations induced are discussed. PMID- 6254673 TI - Metabolic fate of cell surface glycoproteins during immunoglobulin-induced internalization. AB - Goat antibodies directed against a subset of the externally oriented plasma membrane glycoproteins of hepatoma tissue culture (HTC) cells were used to follow the metabolic fate of the membrane antigens and the specifically bound immunoglobulin molecules in this cell type in cultures. Analyses of the immunoprecipitates from cells labeled in situ with neuraminidase and galactose oxidase, followed by reduction with tritiated sodium borohydride, indicate that about 40% of the galactose-labeled plasma membrane glycoproteins are recognized by the antiserum. Fluorescent microscopic analyses of cells treated with fluorescein-conjugated immunoglobulins and analyses of trypsin accessibility indicate that probably all of the antibodies bound to the cell surface are patched and internalized within about 4 hr when the cells are subsequently cultured at 37 degrees C in the presence of rabbit anti-goat immunoglobulins. At the same time, the antigens are also interiorized. Analyses of the cellular localization of the interiorized antigens and antibodies by cell fractionation on Percoll gradients show that the immunoglobulins to the cell surface antigens and the antigens themselves migrate to the same region of the Percoll gradient as lysosomal hydrolases. Although the antibodies bind to the cell surface glycoproteins and bring about patching and interiorization, there is no effect on the degradation of the plasma membrane antigens labeled via the galactose oxidase/borohydride reduction method. Furthermore, the iodinated antibodies directed against these membrane glycoproteins behave in their turnover properties like membrane antigens; the cell-bound specific immunoglobulins have the same half-life as the membrane glycoproteins. When the cells that had been reacted with the goat antibodies to membrane glycoprotein were cultured in the presence of rabbit anti-goat immunoglobulins, degradation of the former antibodies was effectively decreased. Similar results were obtained with concanavalin A and antibodies directed against this plant lectin. PMID- 6254674 TI - Annulate lamellae in frog adenohypophysis under normal and experimental conditions. AB - Cytoplasmic annulate lamellae have been observed in frog (Rana ridibunda) adenohypophysis pars distalis from normal spring animals and from others which were submitted to experimental conditions inducing selective activation of different cell types. Cell activation, because of either the normal active period in the frog cycle or the experimental treatments, seems to be correlated with the occurrence annulate lamellae. These annulate lamellae consist of a succession of two relatively parallel membranes interrupted periodically by discontinuities similar to nuclear pores. Sometimes they have been observed connected to endoplasmic reticulum. PMID- 6254675 TI - [Fusion of somatic cells in vitro]. PMID- 6254676 TI - [Epithelial tumors of the liver in childhood]. AB - A group of five epithelial hepatic tumours in children includes one adenoma, one embryonic and two mixed hepatoblastomas, and one hepatocarcinoma. The specific features of the histological structure of the above tumours are discussed. PMID- 6254677 TI - [Inflammatory fibrous histiocytoma]. AB - A busky tumour of yellow colour with pus-filled central cavities was removed from the left retroperitoneum of a 54 year old man. Histology revealed it to be a rare variant of fibrous histiocytoma characterized by an extremely large quantity of mature neutrophil granulocytes in all the tumour tissue messively phagocyted by tumour histiocytes. There was no relapse or dissemination when postmortem was performed 5 months after the operation. PMID- 6254678 TI - [Permanent cure of glioblastoma multiforme of the brain with metastases into the axillary lymph nodes]. PMID- 6254679 TI - Myeloperoxidase-catalyzed binding of 3-amino-1-methyl-5H-pyrido[4,3-b]indole, a tryptophan pyrolysis product, to protein. AB - Incorporation of 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), the principal mutagen in a tryptophan pyrolysate, into bovine serum albumin was catalyzed by myeloperoxidase. Hydrogen peroxide was essential for the incorporation reaction and albumin was required for optimal incorporation of Trp-P-2 into protein. Other various proteins, such as histone, lysozyme, cytochrome c, and gamma-globulin could also incorporate Trp-P-2, but poly(L-Arg), poly(L-Lys), and poly(L-Glu) could not. The incorporation of Trp-P-2 into albumin was inhibited by L-tyrosine and L-tryptophan, but not by other amino acids. Trp-P-2 incorporated into albumin was not released from the protein by treatment with 0.3 N HCl, or 0.3 N NaOH for 2 h at 35 degrees C, or with 1% sodium dodecylsulfate for 2.5 min at 100 degrees C. On electrophoresis on polyacrylamide containing sodium dodecylsulfate or urea and on chromatography on Sepharose CL-6B in 6 M guanidine/HCl, Trp-P-2 incorporated into albumin or lysozyme migrated with these proteins. These findings indicate that Trp-P-2 is covalently bound to these acceptor proteins. PMID- 6254680 TI - [The combined effect of selenium deficiency and viral infection on the myocardium of mice (preliminary study) (author's transl)]. PMID- 6254681 TI - The role of WR-2721 in radiotherapy and/or chemotherapy. AB - This report summarizes the present status of the proposed use of WR-2721 (S-2-(3 aminopropylamino)-ethylphosphorothioic acid) acid) in radiotherapy and/or chemotherapy. This drug selectively concentrates in normal tissues, both in vivo and in vitro, but is passively absorbed by virtually all of the solid tumors which have been studied. In vivo this drug can increase the resistance to radiation or alkylating agents (nitrogen mustard, cis-platinum, cyclophosphamide, and L-phenylalamine mustard) by factors of up to 3, while leaving the solid tumors to suffer the full effects of either treatment. PMID- 6254682 TI - Phase I clinical studies with WR-2721. AB - Toxicity studies of S-2-(3 aminopropylamino)-ethylphosphorothioic acid (WR-2721) access patients in remission following radiation therapy. The dose has been escalated from 25 to 250 mg/m2 without significant symptoms. Inconsistent variation in the systolic blood pressure in some patients has been observed over an 8-10-point range without producing any symptoms. The variation could be within the patient's normal range. However, tests are planned to rule out cardiac toxicity or peripheral vascular reaction. Combining WR-2721 with conventional radiotherapy is contemplated by intravenous injection of the drug 20-30 minutes before irradiation. This will start as weekly injections, and the number of weekly injections will be increased progressively. Animal studies suggest that the level already safely reached could give significant protection to the normal tissues without protecting tumor. PMID- 6254683 TI - [Comparative induction of viral antigen synthesis in various types of cells infected by polyoma virus]. AB - Induction of synthesis of the viral antigens T and V during polyoma virus infection was studied in primary Mouse and Hamster kidney and brain cultures, as well as in various types of human cells. The results show that: (1) Despite a very low percentage of positive cells by immunofluorescence, Hamster brain cells produced more viral antigen than kidney cells, as opposed to what was found in Mouse brain cells. (2) Most human cells produced neither T nor V antigens. Conversely, a large number of brain cells synthesized the T antigen very early after infection. PMID- 6254684 TI - Phase II trial of prednimustine (NSC-134087) in the treatment of small-cell anaplastic carcinoma of the lung. AB - In a phase II trial, the clinical activity of prednimustine, an ester of chlorambucil and prednisolone, was evaluated in 28 patients with small-cell anaplastic carcinoma of the lung. Prednimustine was given at dose levels ranging from 130 to 220 mg/m2/daily for 5 days every 3 weeks. Among 19 previously treated patients no responses were observed, while responses of 2, 2, and 3 months' duration were seen in three of nine previously untreated patients more than 70 years old. The toxicity took the form of mental disturbances in six patients, while the hematologic toxicity was mild. The therapeutic effectiveness of prednimustine in small-cell carcinoma of the lung is thus limited although some activity is observed in previously untreated patients. PMID- 6254686 TI - The role of adenosine in the regulation of coronary blood flow. PMID- 6254685 TI - Failure of intensive combination therapy (cyclophosphamide, adriamycin, 5 fluorouracil) to control adenocarcinoma or large-cell anaplastic carcinoma of lung. AB - Eleven patients with advanced adenocarcinoma of lung and six patients with large cell anaplastic carcinoma of lung were treated with combination chemotherapy using cyclophosphamide 1 g/m2 i.v., adriamycin 30 mg/m2 and 5-FU 500 mg/m2 i.v. on days 1 and 8, of a 28 day cycle. In neither group did any patient achieve a complete remission; 1 patient achieved a partial response in each group, and the rest showed no evidence of response. The duration of survival of the responding patients in each group was not significantly longer than those of the non responders. Toxicity and side effects were considerable in all patients. This study demonstrates that these tumour types are refractory to this form of intensive combination chemotherapy. A literature review suggests that other forms of combination chemotherapy are usually equally ineffective. PMID- 6254687 TI - Mechanism(s) of altered mitochondrial calcium transport in acutely ischemic canine hearts. AB - Studies were undertaken to determine the mechanisms leading to altered mitochondrial function in ischemic myocardium. A new procedure has been developed to routinely isolate 60-70% of the total mitochondrial protein from heart tissue. After 1 hour of ischemia, mitochondria exhibit decreases of more than 50% in phosphorylating respiration for both NADH- and succinate-linked substrates compared to controls. However, no significant decreases in the efficiency of mitochondrial ATP synthesis (ADP:0) or ATPase activity are observed. Rates of substrate-driven Ca2+ uptake exhibit decreases greater than that seen with phosphorylating respiration with incomplete uptake and premature release of Ca2+. Spectrophotometric measurements in ischemic heart reveal rapid oxidation or loss of mitochondrial NADH with marked "swelling" of the inner membrane compartment; both changes parallel the loss of Ca2+. Significant losses in intramitochondrial adenine nucleotides also are found. Mitochondrial retention of accumulated Ca2+ can be restored by addition of small amounts of exogenous adenine nucleotides (ATP or ADP) with concomitant attenuation of both NADH oxidation and "swelling." The data indicate that, following 1 hour of ischemia, the efficiency of mitochondrial ATP production is still relatively intact whereas both electron transport chain activity and calcium transport are severely compromised. These decreases appear to be related to selective membrane damage in the mitochondrial inner membrane. PMID- 6254688 TI - Regulation of the postsynaptic alpha-adrenergic receptor in rat mesenteric artery. Effects of chemical sympathectomy and epinephrine treatment. PMID- 6254689 TI - beta-Adrenergic regulation of total systemic intravascular volume in the dog. PMID- 6254690 TI - Pharmacology of platelet-affecting drugs. PMID- 6254691 TI - Responsiveness of the coronary circulation to brief vs sustained alpha-adrenergic stimulation. AB - The effects of brief and sustained pharmacologic alpha-adrenergic stimulation on the coronary arterial circulation were compared in awake pigs. Phenylephrine was administered into the left anterior descending coronary artery (LAD) either as a bolus (eight pigs) or as a 15-minute infusion (eight pigs), with myocardial blood flow measured by the radioactive microsphere technique. Flow in the distribution in the LAD was compared with flow in myocardium perfused by the left circumflex coronary artery (LCF) as the ratio LAD/LCF. This technique corrects for systemic factors capable of modifying oxygen demand, and hence myocardial blood flow, in both zones. After a phenylephrine bolus (50-100 microgram), LAD/LCF fell significantly, whereas no change was observed after the sustained infusion (5-10 and 50-100 microgram/min). Four additional pigs were pretreated with i.v. adenosine to raise myocardial blood flow in excess of demand before sustained stimulation. In this setting LAD/LCF fell significantly during the sustained phenylephrine infusion. Brief alpha-adrenergic stimulation could overcome normal flow regulatory mechanisms and resulted in constriction of coronary resistance vessels. Such changes did not occur after sustained stimulation and suggest an ability of the coronary circulation to offset chronic vasoconstrictive effects. When the myocardium is overperfused, sustained alpha-adrenergic stimulation does not jeopardize myocardial oxygenation and its vasoconstriction potential is unmasked. PMID- 6254692 TI - Cardiorespiratory effects of inhalant occupational exposures. PMID- 6254693 TI - Novel reagent and method for direct determination of chloride in serum with a centrifugal analyzer. AB - We report a novel reagent containing ferric perchlorate, perchloric acid, and polyoxyethylene (23) lauryl ether (Brij 35) with which the concentration of chloride in serum can be measured. We applied this reagent to use with a centrifugal analyzer (CentrifiChem 400) in a dynamic bichromatic procedure, resulting in broad linearity of the standard curve (0-180 mmol/L), short analysis time (1 min), and little interference from bilirubin, hemoglobin, turbidity, or bromide ions. The reagent is simple, contains no mercury, and the combination of low acid concentration and surfactant prevents serum protein precipitation. Precision is good (for x- = 93 mmol/L, CV = 1.55%), and results correlate well with those obtained by coulometry (r = 0.974). PMID- 6254694 TI - Sodium 1,4-piperazinediethanesulfonate monohydrate ("Pipes") for measurement of pH of blood and other physiological media. PMID- 6254695 TI - Use of Sep-pak cartridges for urinary steroid extraction: evaluation of the method for use prior to gas chromatographic analysis. AB - A method is described for the rapid and quantitative extraction of free and conjugated steroids from urine using Sep-pak C18 cartridges. The method was evaluated by determining the efficiency of recovery of (1) radiolabeled steroid glucuronides, (2) radiolabeled steroids freed by enzymatic hydrolysis, (3) steroid sulphates, (4) selected reference neutral free steroids of varied structure and polarity, and (5) oestrogens. In all cases the cartridges gave results equal to or better than those obtained by solvent or Amberlite XAD-2 extraction methods. Each urine extraction could be completed in 2-3 minutes and no further purification of extracts was required prior to derivatisation and gas chromatographic analysis. PMID- 6254696 TI - Increased aldosterone secretion induced by sulpiride. AB - Sulpiride induces an increase in plasma prolactin and a simultaneous increase of aldosterone release in man. In isolated and superfused bovine adrenal glands, prolactin does not increase aldosterone production even in high concentrations, whereas sulpiride induces a significant and long lasting increase in the production of this hormone and a concomitant increase in the tissue levels of cAMP. This suggests a direct effect on the biosynthesis of aldosterone. PMID- 6254697 TI - A comparison of nephrogenous cyclic AMP, total urinary cyclic AMP and the renal tubular maximum reabsorptive capacity for phosphate in the diagnosis of primary hyperparathyroidism. PMID- 6254698 TI - Evaluation of the three hour metyrapone test in adults. AB - The prolonged metyrapone test is used to assess the hypothalamic-pituitary adrenal axis. The dynamic responses of cortisol, ACTH and 11-deoxycortisol over the 3 h of the single morning dose metyrapone test have been examined in fourteen normal adult subjects. In every case there was a rapid, sustained fall in cortisol, but the resultant ACTH responses were extremely variable and in two subjects did not exceed values obtained during the control studies. The rise in 11-deoxycortisol was also variable and in several instances occurred without any significant elevation in ACTH. In these cases, the rise in 11-deoxycortisol may be due to a normal level of production of steroids with a shift from cortisol to 1-deoxycortisol induced by the metyrapone. Thus, the hypothalamic-pituitary adrenal axis may not be adequately tested, and this together with the high incidence of unpleasant side effects, makes the 3 h oral metyrapone test unsatisfactory for routine use in adults. PMID- 6254699 TI - Secretion of ACTH, LPH and beta-endophin from human pituitary tumours in vitro. AB - Basal and stimulated secretion of immunoreactive ACTH, LPH and beta-endorphin from four human pituitary tumours has been studied in vitro using a superfused, isolated cell system. Chromatography of cell secretions under acid-dissociating conditions demonstrated that the human tumor cells released immunoreactive peptides with the elution profiles of alpha h (1-39) ACTH, beta h-LPH, gamma h LPH and beta h-endorphin confirming that beta h-endorphin is secreted by human pituitary tumour cells and is not formed by enzymic cleavage from beta h-LPH in blood. No alpha- or beta h-MSH, nor any higher molecular weight forms of ACTH or LPH were detected. The cells from all four tumours responded to stimulation with rat stalk-median eminence extract (SME) and synthetic AVP with a concomitant release of ACTH, beta-LPH, gamma-LPH and beta-endorphin. In contrast to the isolated rat anterior pituitary cells, the pattern of responses to SME and AVP were indistinguishable and the release provoked by rat SME could be accounted for virtually entirely by its vasopressin content. No stimulation of release was observed when the cells were exposed to a variety of biogenic amines. Addition of hydrocortisone to the perfusion buffer of two tumours resulted in a slow inhibition of both basal and stimulated ACTH and LPH release. These data demonstrate that human pituitary tumour tissue from patients with Cushing's disease and Nelson's syndrome can be studied in vitro and that such studies may contribute to a greater understanding of the aetiology of these diseases. PMID- 6254701 TI - Langer-Giedion syndrome and additional congenital malformations with interstitial deletion of the long arm of chromosome 8 46, XY, del 8 (q 13-22). AB - Deletion of the long arm of chromosome 8 was found in a mentally retarded boy with typical features of the Langer-Giedion syndrome (TRP syndrome type II). Additional malformations were colobomata of the iris and partial syndactyly of the 4th and 5th fingers. PMID- 6254700 TI - Acute facial paralysis: a virological study. AB - A serological study using the complement fixation reaction for herpes zoster virus (HZV) and herpes simplex virus (HSV) was carried out on 120 patients with Bell's palsy and 5 with Ramsay-Hunt syndrome. Three Bell's palsy patients (2.5%) showed a significant HZV antibody titre rise. In no case was a rise of HSV antibody titre observed. Two Ramsay-Hunt patients showed a significant rise of HZV antibody titre. Rise of HSV antibody titre was not observed in this group either. The Monosticon test to exclude infectious mononucleosis, proved to be negative in all cases of Bell's palsy. In 2 cases of Bell's palsy, a biopsy specimen for virus isolation was obtained during a decompression operation. No virus could be cultured from the epineurium of the first patient. That of the second patient was found to contain HSV type I. There was no serological evidence of a HSV antibody titre rise. PMID- 6254702 TI - Glomus tumours: a clinico-pathological survey. PMID- 6254704 TI - Correlation of disease activity and Clq-binding immune complexes with the neutrophil inclusions which form in the presence of SLE sera. PMID- 6254703 TI - Mechanisms of macrophage activation. PMID- 6254705 TI - Lymphocyte cyclic AMP levels in primary hypogammaglobulinaemia: lack of correlation with response to phytohaemagglutinin. AB - Normal levels of lymphocyte cyclic AMP were found in fourteen of fifteen patients with primary hypogammaglobulinaemia. One patient with adult-onset hypogammaglobulinaemia had low cyclic AMP levels with a very poor rise after prostaglandin E1 stimulation. Five of the patients had severely depressed thymidine uptake by their phytohaemagglutinin-stimulated lymphocytes but there was no significant difference between their lymphocyte cyclic AMP levels and those of patients with normal lymphocyte responses. Removal of monocytes from concanavalin A-stimulated lymphocyte cultures from three of these patients did not affect the severe depression of leucine uptake. These findings indicate that the depression of lymphocyte response to mitogens seen in some patients with late onset primary hypogammaglobulinaemia is not due to raised levels of lymphocyte cyclic AMP; and not usually due to prostaglandins released by monocytes in the cultures. PMID- 6254706 TI - Enzyme release and superoxide anion production by human alveolar macrophages stimulated with immunoglobulin E. AB - Human alveolar macrophages specifically released lysosomal beta-glucuronidase and neutral proteases when successively incubated with IgE, and then, for 30 min, with anti-IgE. Superoxide anion O2- generation was obtained when anti-IgE opsonized zymosan was added to IgE-incubated cells. Macrophages from smokers excreted twice as much enzymes and superoxide as cells from non-smokers. It was possible to induce the specific release of beta-glucuronidase with normal alveolar macrophages successively incubated with the serum of patients allergic to house dust or to grass pollen and then with the specific allergen. This characteristic opens the field to a direct test for allergic sera by analogy with the allergen-induced degranulation test of sensitized basophils. PMID- 6254707 TI - Non-specific inhibition by virus particles of human lymphocytes mitogenesis. AB - Many different types of virus particles including avian retroviruses, Friend leukaemia virus and Sendai virus are able, when coincubated with human peripheral blood lymphocytes in the presence of mitogens or alloantigens, to inhibit the usual proliferative responses that normally ensue. These effects are independent of infection and can be obtained using u.v.-inactivated viruses as well as virus lymphocyte combinations which are non-physiological in nature. Lymphocytes which are preincubated with viruses for as little as 5 min, and then washed free of unbound virus, are significantly impaired in terms of ability to react to mitogenic stimulus. These events may be mediated, in part at least, by the virus induced elaboration by mononuclear cells of a factor with lymphocyte inhibitory potential. PMID- 6254708 TI - Monoclonal cryoimmunoglobulin with anti-cytomegalovirus activity associated with T cell chronic lymphocytic leukaemia. AB - A patient with chronic T cell lymphocytic leukaemia developed a monoclonal immunoglobulin (IgG3 kappa = 14 g/l) which was in part cryoprecipitable. At the same time, a subclinical CMV infection occurred which was associated with a neutropenia and thrombocytopenia, and which led to a rise in anti-CMV antibodies. The F(ab')2 fragment of IgG3 kappa, obtained by enzymatic cleavage, was examined for several antiviral activities and it was found to have a strong anti-CMV activity using the immunofluorescence test with anti-kappa conjugate. This is one of the few examples of a cryoglobulin with specific antiviral activity. The leukaemia, possibly together with immunosuppressive therapy, may have been responsible for the uncontrolled proliferation of the clone producing the cryoimmunoglobulin. PMID- 6254709 TI - Olfactory disturbances in Parkinsonism. AB - Disturbance of smell should be regarded as a common symptom of Parkinson's disease. It often presents as a precursor of the motor disability. The common underlying cause might be the deficiency of catecholamines in the brain of Parkinson patients, especially in the mesolimbic projection areas. PMID- 6254710 TI - Pseudotumor cerebri due to intracranial arteriovenous malformation. AB - The authors present a case history of a meningeal arteriovenous malformation, presenting as a pseudotumor cerebri syndrome. Subarachnoid hemorrhage did not occur and brain configuration was normal on CT-scan. The pathogenesis of papilledema in this case is discussed. Probably the cause must be sought in the massive overload of the venous return, resulting in increase of cerebral blood volume, impairment of CSF absorption and increase of CSF production. The common denominator and final pathway in intracranial hypertension, also directly responsible for papilledema, is CSF hypertension. PMID- 6254711 TI - Treatment of minor head injuries. AB - The results of various forms of treatment of patients with minor head injuries have been examined. The number and frequency of post-concussional sequelae was markedly reduced by treatment which included information, explanation and encouragement. Dizziness, loss of hearing and loss of balance were related to external lesions to the vestibular system caused by injuries to the parieto temporal region of the skull. PTA proved to be a reliable indicator of the severity of cerebral concussion and correlated with post-concussional sequelae and periods of disability. Other factors which increased the number and frequency of post-traumatic sequelae, especially those related to stress before the accident, could be counteracted by better treatment of the patient. The results bear out the hypothesis that post-concussional sequelae start off on an organic basis (PTA) and that persistent sequelae after minor head injuries are also caused by psychogenic, and especially by iatrogenic factors. PMID- 6254712 TI - Clinical applications of evoked responses: a survey. AB - Evoked responses were first described in the late forties. In the late fifties, technology had so far advanced that the method became practically useful in clinical applications. Descriptions of the normal response and the influence of age and the effect of attention were extensively studied. There are marked interindividual and interlaboratory differences, partly explained by differences in test set-up. This is why it is still necessary that every laboratory, using its own test set-up, should determine its own standard values in normal test subjects. The value of ER studies in clinical diagnosis may be summarized as follows: --ophthalmology, organic psychiatry, neuropaediatrics, multiple sclerosis, uraemia: ER studies often supply important diagnostic information; - local lesions of the cerebral hemispheres, peripheral nerves and spinal cord, coma: ER studies can be useful as source of supplemental diagnostic information; -non-organic psychiatry and psychology: ER studies are still of minor practical value in individual clinical diagnosis. Research into applications of spinal evoked potentials and brain stem potentials is still in its initial phase. PMID- 6254713 TI - The application of visually evoked cerebral potentials in ophthalmological diagnosis. AB - A short survey is presented of what can be done with electrophysiological techniques in ophthalmological diagnosis. It is stressed that more investigation has to be done to elucidate the discrepancies between electrophysiological and psychophysical disturbances. These discrepancies can be used for the differential diagnosis. More, though still too little, is known about differences between a disturbance of latency time and that of amplitude. It seems that latencies are more disturbed in active pathological processes like demyelination, compression of nerve fibres and oedema, whereas isolated reduction of amplitudes occurs in optic atrophies. Some optic nerve diseases are found to be combined with ERG abnormalities, such as tobacco-alcohol neuropathy and some hereditary diseases. PMID- 6254714 TI - Circumferential cranio-reduction. AB - A simple procedure for reduction of the skull capacity is presented. This operation is indicated in cases where a hygroma had produced a marked disproportion between brain volume and skull capacity. A 'double drain' should be applied for 10-14 days in order to obliterate the intermembranous space optimally. PMID- 6254716 TI - Relative roles of radionuclide scanning and radiographic imaging in eosinophilic granuloma. AB - Twenty-four skeletal lesions were studied in seven patients with eosinophilic granuloma by radiographic skeletal surveys and radionuclide bone imaging. The radiographs detected 22 (92%) of these lesions and missed only two, whereas the scintiscans identified only 16 (67%) of these lesions, and missed eight. Radiographic skeletal survey and radionuclide bone imaging are complementary procedures in detecting bone lesions in bone marrow disorders, including eosinophilic granuloma. Use of either method alone is fraught with the danger of missing bone lesions of eosinophilic granuloma. PMID- 6254715 TI - Diagnostic CSF analysis in neurological practice. AB - In order to establish the diagnostic value of clinical chemical analyses of C.S.F. samples, the C.S.F. data from seven hundred patients have been evaluated. The authors discuss the influence this investigation has exerted on their differential diagnostic evaluation. PMID- 6254717 TI - Calcified ovarian tumor causing discrete photopenia on bone scan. PMID- 6254719 TI - Perinatal viral infections. PMID- 6254718 TI - Mechanism of uptake of bone imaging isotopes by skeletal metastases. PMID- 6254721 TI - Diet and coronary heart disease. PMID- 6254720 TI - Absence of opiate and histamine H2 receptor-mediated effects of clonidine. AB - The possibility that clonidine might exert some of its effects via opiate or histamine H2 receptors has been suggested from observations in animals and man. We undertook a double-blind, randomized study in six normal subjects, comparing the effects of 0.2 mg intravenous clonidine after pretreatment with 300 mg cimetidine, 0.8 mg naloxone, and saline. There was no attenuation of the hypotension, bradycardia, sedation, inhibition of salivary flow, or reduction in plasma catecholamines after cimetidine and naloxone, but the fall in plasma catecholamines ater clonidine correlated with blood pressure, sedation, and salivary flow, suggesting a central adrenergic mechanism for these effects. It is not known whether cimetidine can cross the blood-brain barrier after short-term dosing. We conclude that in normotensive subjects the short-term effects of intravenous clonidine are probably not mediated by an action at peripheral histamine H2 or central opiate receptors. PMID- 6254722 TI - Management of acute infectious diarrhea. PMID- 6254723 TI - Studies on Nonoxynol-9. II. Intravaginal absorption, distribution, metabolism and excretion in rats and rabbits. AB - Some pharmacological aspects of Igepal CO-630, used by some pharmaceutical companies as the source of nonylphenoxypoly (ethyleneoxy) ethanol (Nonoxynol-9, N 9) in various spermicidal formulations, were studied. It was found that Igepal CO 630 contains at least 13 components, 70% having molecular weights near that of N 9. After intravaginal administration, the detergent is rapidly and quantitatively absorbed through the vaginal wall into the systemic circulation. The rate of vaginal absorption of N-9 depends on the vehicle in which the detergent is carried. Once in the blood, N-9 is excreted by liver-bile-feces and the kidney urine routes, the first being more effective in rats, the latter in rabbits. Following intravaginal or intraperitoneal injection of radioactive N-9, the highest content of radioactivity was found in the liver and kidney. The detergent was detected in the milk of lactating rats and the serum of their pups within two hours after the intravaginal dose. PMID- 6254724 TI - Kallikrein-kinin system and hypertension. PMID- 6254725 TI - Intramolecularly hydrogen-bonded peptide conformations. AB - Over the past few years the possible occurrence of intramolecularly hydrogen bonded structures in linear and cyclic peptides has attracted increasing attention. In this review emphasis is given to solid-state studies, particularly by X-ray diffraction and infrared absorption techniques. Conformational energy calculations are also considered. The discussion is focused both on model peptides and biological activity polypeptide molecules. The tetrapeptide system (Formula: see text), examined allows one to discuss the extended C5 structure and the various folded conformations, namely the C7 (gamma-turn), C8, C10 (beta turn), C11, and C13 conformations. The four latter forms may include cis peptide configurations. The oxy-analogs to the C7, C10, and C13 conformations and structures containing bifurcated hydrogen bonds are also discussed. The last sections describe intramolecularly hydrogen-bonded peptide structures involving: (1) a side-chain group, (2) the N-protecting group (in synthetic model compounds), and (3) a beta-amino acid. PMID- 6254726 TI - Free radical initiation in proteins and amino acids by ionizing and ultraviolet radiations and lipid oxidation--part III: free radical transfer from oxidizing lipids. AB - Parallels and similarities in chemical and functional damage to proteins by ionizing and uv radiations and oxidizing lipids have been recognized for some time. However, only recently have oxidizing lipids been shown directly by electron spin resonance to be radiomimetic also in their capacity for protein free radical production. Free radicals play a key role in the transformation of energy to molecular and cellular damage. It is thus of critical importance to elucidate the general mechanisms of free radical formation and reactions in proteins in order to understand protein involvement in various pathological conditions and in food deterioration. Accordingly, this review is a detailed comparison of gamma-radiation, UV radiation, and lipid oxidation for what is presently known concerning (1) the specific modes of energy deposition and free radical formation, (2) the free radicals formed in proteins and amino acids, and (3) the typical damage correlating with these radicals. PMID- 6254727 TI - Sensitivities of clinically significant organisms to four cephalosporins, ampicillin and mecillinam. AB - Specimens received at a district laboratory over a period of 4 months were investigated for determination of the sensitivities of common pathogens to 4 cephalosporins, ampicillin and mecillinam. A total of 1035 freshly isolated clinically significant organisms was studied. When sensitivities of all pathogens were considered, the majority were found to be resistant to ampicillin and mecillinam and sensitive to the cephalosporins. Sensitivity figures changed considerably when individual groups of organisms were considered. The great majority of urinary pathogens were sensitive to mecillinam, but not to ampicillin. This pattern was reversed when respiratory pathogens were considered. Only a few pathogens from wound swabs were sensitive to either ampicillin or mecillinam. All the cephalosporins tested showed much wider spectrum of activities. Of all antibiotics tested, only cefoxitin was active against the vast majority of Bacteroides spp. These findings are discussed in relation to the clinical uses of these antibiotics. PMID- 6254728 TI - Formyl peptide chemotactic receptors of leukocytes and macrophages. PMID- 6254729 TI - Hormones, receptors, and cyclic AMP: their role in target cell refractoriness. PMID- 6254730 TI - Cooperative interaction between mitochondrial and nuclear genomes: cytochrome c oxidase assembly as a model. PMID- 6254731 TI - Stimulation of DNA synthesis in quiescent cultured cells: exogenous agents, internal signals, and early events. PMID- 6254732 TI - [Reflections on three cases of "apparently non-functional" malignant nesidioblastoma, or "silent malignant pancreatic apudomas" (author's transl)]. PMID- 6254733 TI - Isolation and characterization of a new family of mobile dispersed genetic elements, mdg3, in Drosophila melanogaster. AB - The properties of a new family of mobile dispersed genetic elements, mdg3, are described. Mdg3 is represented by a DNA fragment of about 5.5 kb long which is framed with two repetitive sequences 300-500 base pairs in length. Virtually the whole region of mdg3 including the repetitive sequences is transcribed and, as the result, 26S poly(A)+RNA is formed. The repetitive sequence is present at least at the 3'-end of a major 26S transcript. Both strands of mdg3 are transcribed, but one direction is predominant. Besides 26S RNA, a minor transcript, 15S poly(A)+RNA, can be observed. 15S RNA dose not contain sequences corresponding to the middle of mdg3. Possibly it is formed from 26S RNA by means of splicing. About 15 copies of mdg3 are present in the genome of embryonic cells and polytene chromosomes. Different copies of mdg3 are identical but surrounded with different DNA sequences. In culture cells, the gene is amplified and the number of copies is increased approximately 13 times. Mdg3 is localized in 15-17 sites on different chromosomes of D. melanogaster. Its location varies from one animal to another. The properties and possible nature of mobile dispersed genetic elements are discussed. PMID- 6254735 TI - [Tumor of glomus jugulare- Report of 2 cases and a review of literature (author's transl)]. PMID- 6254734 TI - Circadian-stage-specified effects of a synthetic short chain ACTH-1-17 (HOE 433) on blood leukocytes and corticosterone secretion in mice. AB - A synthetic short chain ACTH, ACTH-1-17 (HOE 433 = Synchrodyn 1-17), beta-ala1, lys17 corticotropin (1-17)heptadecapeptide-4-N-butylamide, was tested for activity at the anticipated circadian stage of highest adrenal corticosterone responsiveness (22-HALO) in BALB/c mice. Statistically significant dose-response relations were demonstrated both in vitro (corticosterone production by adrenals incubated in Krebs-Ringer solution) and in vivo (increases in the serum corticosterone concentration). Leukocyte counts in mice injected with this ACTH showed statistically significant decreases (as compared to controls) for all kinds of cells except the neutrophil and medium-sized lymphocyte. PMID- 6254736 TI - [Analysis of the effect of camptothecin as an adjunct treatment of primary liver cancer (author's transl)]. PMID- 6254738 TI - Influence of ranitidine on antipyrine pharmacokinetics in healthy volunteers. PMID- 6254737 TI - Hormonal influences on chemical carcinogenesis: studies with the aflatoxin B1 hepatocarcinoma model in the rat. AB - The role of adrenocorticotropin, cortisol, and corticosterone on chemical carcinogenesis was investigated using the rat aflatoxin B1 hepatocarcinoma model. The animals were divided into untreated controls and various experimental groups receiving the carcinogen alone or the carcinogen with a hormone. Animals lost during the treatment period died mostly of massive hepatic necrosis. The results following 65 weeks of observation show that: (1) hormones decrease the toxicity of aflatoxin B1; (2) adrenocorticotropin possibly exerts its influence on aflatoxin B1 hepatocarcinogenesis through adrenal stimulation, and (3) in aflatoxin B1-adrenocorticotropin treated animals, hepatocellular carcinoma, cholangiocarcinoma, and malignant lymphoma may be observed. PMID- 6254739 TI - Mullerian adenosarcoma of uterine cervix. Report of a case with rapidly fatal outcome. AB - Mullerian adenosarcoma of the uterus has been regarded as a neoplasm of low-grade malignancy; notwithstanding frequent local recurrences, sometimes after long intervals, the overall prognosis of the three dozen or so tumors reported in the literature has been good. This report documents an unusual clinical course of an adenosarcoma of uterine cervix occurring in an 80-year-old patient. Following clinically disease-free period of 25 months after hysterectomy, the tumor recurred in vaginal vault, grew with devastating rapidity, and proved fatal within 4 months. At autopsy, massive sarcomatosis peritonei and discrete tumor nodules involving the stomach and bowel were found. PMID- 6254740 TI - Trophoblastic pseudotumor: An illustrative case. AB - A case of trophoblastic pseudotumor of the uterus is presented. Erroneous interpretations of the specimens derived from curettage and hysterectomy resulted in surgery and chemotherapy. Emphasis in this report is on histologic criteria which aid in distinguishing this lesion from choriocarcinoma. Hormone production and persistence of the tumor for several months after curettage are also documented. PMID- 6254741 TI - Ultrastructural aspects of mucinous (colloid) breast carcinoma. AB - Seven cases of mucinous (colloid) breast carcinoma were studied by electron microscopy. In addition to the predictably abundant mucosubstance production, the following observations merit elaboration: 1) absence of myoepithelial differentiation and basal lamina deposition, 2) notably developed cytoplasmic filamentous systems and relatively scarce lysosomes, 3) frequent and apparently well-developed intercellular junctions, and 4) a distinct paucity of vessels in the tumors' stroma. The rather favorable clinical prognosis of mucinous breast carcinoma despite the absence of myoepithelial differentiation and basal lamina deposition parallel observations made on medullary and tubular breast carcinomas, thus confirming that those parameters, however important, are not the sole determinants of an aggresive behavior. The conspicuous cytoplasmic filaments appear to be neither true myoepithelial filaments or tonfilaments. The peculiar arrangement of these contractile proteins and the suspected sarcity of lysosomal collagenases may be reflected in the rather low invasiveness of these carcinomas. Another factor that may impact favorably on the cohesiveness of these neoplastic cell clusters is the presence of abundant and well-developed intercellular junctions. We further speculate that the paucity of stromal vessels in these neoplasms may be the result of as yet unidentified factors that might inhibit angiogenesis. PMID- 6254742 TI - [Site-specific deletions of vector plasmid pBR322]. PMID- 6254743 TI - [Cloning of fragments of simian adenovirus 7 DNA in Escherichia coli bacteria using plasmid vector pBR322]. PMID- 6254744 TI - [Proton magnetic relaxation in studies of the development of burn pathology]. PMID- 6254745 TI - [Blockade of the epithelial cell membrane sodium and chloride channels of frog skin]. PMID- 6254746 TI - Epidemiology of acute gastroenteritis in early childhood in Kenya. VI. Some clinical and laboratory characteristics relative to the aetiological agents. PMID- 6254747 TI - Diagnostic ultrasound in abdominal disease--first experiences in Kenya. PMID- 6254748 TI - [EEG and CAT in astrocytomas grade III-IV (author's transl)]. AB - The relation between C.A.T., EEG, echoencephalography and clinical data was studied in 33 patients with astrocytoma grade III-IV. The diagnostic and localizing possibilities of the EEG were evaluated. The occurrence of EEG signs (focal delta-activity, asymmetry of normal rhythms, frontal intermittent rhythmic delta-activity etc.) was related to the C.A.T.-findings. A prognostic value of the EEG could be established in this group of patients. The results of the A-scan echoencephalography were compared with the midine displacements as shown on the C.A.T. It is pointed out that comparative studies of C.A.T. and EEG are valuable only when clinically homogeneous groups are taken into consideration. The necessity of such studies for a better understanding of the EEG is stressed. PMID- 6254749 TI - [On the proposed mechanism of action of antidepressants (author's transl)]. AB - Classical antidepressants (MAOI, uptake inhibitors) increase monoamine levels in the synaptic cleft. However other presynaptic mechanisms of action have been proposed: increase in release (amineptin), blockade of presynaptic alpha adrenoceptors (mianserin). A postsynaptic approach is also possible: stimulation of beta-receptor (salbutamol), blockade of muscarinic receptor (quinupramine). Moreover the side effects have been correlated to a blockade of postsynaptic receptors: alpha 1 for aorthostatic hypotension, H1 for sedation and muscarinic for anticholinergic effects. However these effects do not explain the delay for the clinical efficiency of antidepressants. A desensitization of presynaptic receptors or a decrease in beta-postsynaptic receptors have been advanced. In fact a possible pharmacokinetic explanation for the delay of clinical efficiency, i.e. the necessary delay to reach brain steady state level, is possible. Finally the presence of imipramine binding sites might be a new approach of the mechanism of action of antidepressants. PMID- 6254750 TI - Growth stimulative effect of parathyroid hormone, calcitonin and N6,O2'-dibutyryl adenosine 3';5'-cyclic monophosphoric acid on chick embryonic cartilage cultivated in a chemically defined medium. AB - PTH (0.5 unit/ml) and CT (0.5 unit/ml) strongly stimulated the in vitro growth of the chick embryo femur in terms of elongation and dry weight increase as well as an increase in the protein, hexosamine, hydroxyproline, DNA and RNA content of the femur. A synergistic effect was observed when PTH and CT were simultaneously added to the medium, suggesting that the mechanism of the growth stimulating effect of one of these hormones might be different from that of the other. The exposure of PTH to the femur caused an increase in cyclic AMP content. The direct addition of dibutyryl cyclic AMP (1 mM) to the medium mimicked the effect of PTH on the cartilage. PTH, therefore, seems to stimulate the growth of cartilage via the increase in cyclic AMP content of the femur. CT had no effect on the cyclic AMP content of the femur. PMID- 6254751 TI - Selective activation of diaphyseal chondrocytes by parathyroid hormone, calcitonin and N6,O2-dibutyryl adenosine 3',5'-cyclic monophosphoric acid in proteoglycan synthesis of chick embryonic femur cultivated in vitro. AB - We have found that the developmental stage of chondrocytes in the chick embryo femur is sensitive to the action of PTH, CT and dibutyryl cyclic AMP in stimulating proteoglycan synthesis as estimated by the incorporation of radioactive inorganic sulfate. PTH treatment of the cartilage resulted in dramatic stimulation of the proteoglycan synthesis in the diaphysis, which is composed of rather old non-dividing hypertrophied chondrocytes with much lower proteoglycan-synthesizing activity than younger dividing cells in the epiphysis and metaphysis. No or slight stimulation was observed the epiphysis and metaphysis. Dibutyryl cyclic AMP produced much the same effect. CT also stimulated the proteoglycan synthesis only in the diaphysis but the stimulation was less potent (133% of control) than PTH (650% of control) or dibutyryl cyclic AMP (625% of control). The hormones and dibutyryl cyclic AMP, therefore, seem to activate the proteoglycan synthesis specifically in rather old chondrocytes of the diaphysis. A synergistic effect of PTH and CT suggesting a different stimulating mechanism was observed in the diaphysis. PMID- 6254752 TI - Prolonged antidiuresis by 1-desamino-8-D-arginine vasopressin (DDAVP): correlation to its plasma levels and nephrogenous cyclic AMP production. AB - In an attempt to clarify the mechanism responsible for the prolonged effect of DDAVP (1-desamino-8-D-arginine vasopressin), plasma levels of DDAVP and nephrogenous cyclic AMP were determined in patients with diabetes insipidus after a single intranasal administration of 10 micrograms of DDAVP. Plasma DDAVP levels were uniformly elevated within 30 min, and showed a peak ranging from 5.6 to 25.0 pg/ml between 30 and 120 min. The subsequent time-course of plasma DDAVP differed however, from patient to patient, and was irregular in most of them. In all of the patients whose plasma DDAVP dropped below 1.0 pg/ml, antidiuresis was still observed. Although the mean basal level of nephrogenous cyclic AMP in patients with diabetes insipidus was not significantly different from that in control subjects, the administration of DDAVP resulted in a 2-fold increase. A negative correlation between nephrogenous cyclic AMP and free water clearance was obtained. These results suggest that the long-acting nature of DDAVP may be attributed, in addition to its gradual absorption from nasal mucosa and slow metabolic clearance, to a higher or persistent biological activity at the receptor site in the kidney and that a nearly physiological level of antidiuretic hormone may cause de novo synthesis of cyclic AMP in the kidney and exert its biological action. PMID- 6254753 TI - Pancreatic islet cell tumors found in rats given alloxan and nicotinamide. AB - Morphological and biochemical studies were performed in pancreatic islet cell tumors found in rats given alloxan (40 mg/kg) and nicotinamide (305 mg/kg). Complete serial sections of the whole pancreas, combined with planimetric analysis, uncovered islet cell tumors in 5 of 7 rats which were killed 10 to 14 months after treatment. Hypoglycemia associated with hyperinsulinemia was found in a rat which developed a tumor which consisted of cells which reacted lightly with aldehyde fuchsin. Another rat developed a gross tumor which was composed of cells stained deeply with aldehyde fuchsin. However, flat insulin response to glucose associated with glucose intolerance was found in this rat. In addition to B cells, a few A and D cells were found within the two tumors. The present study suggests that pancreatic islet cell tumors found in rats given alloxan and nicotinamide are composed of at least three endocrine cell populations, although the majority of tumor cells are insulin-producing B cells. PMID- 6254754 TI - Cyclic AMP in non-toxic nodular goiter. AB - Cyclic AMP concentrations in a non-toxic nodular goiter were measured by means of the radiocompetitive protein-binding assay. It has been shown that cold thyroid nodules contain a higher concentration of cAMP than the macroscopically normal, extra-nodular thyroid tissue. PMID- 6254755 TI - A controlled study of ACTH therapy in infantile spasms. AB - A controlled study of 5 patients with infantile spasms was performed to determine the effectiveness of corticotropin (ACTH) treatment. Patients were monitored serially, using a time-synchronized polygraphic and video system. Serum cortisol levels were determined by radioimmunoassay. Four patients showed total cessation of seizures and normalization of the EEG on low-dose ACTH therapy. Two of these patients became hypertensive, requiring discontinuance of ACTH. Serum cortisol levels increased markedly in all patients after initiation of ACTh therapy. There appeared to be no consistent difference in serum cortisol levels between patients receiving 20 units/day of ACTH and those receiving 30 or 40 units/day, and there was no difference in cortisol levels in those patients who became hypertensive and those who did not. PMID- 6254756 TI - Steroid hormone production by mammalian adrenocortical dispersed cells. PMID- 6254757 TI - Structure of the 5-S ribosomal RNA gene and its adjacent regions in Torulopsis utilis. AB - A DNA segment spanning one repeating unit of ribosomal RNA(rRNA) genes in a yeast strain, Torulopsis utilis, has been cloned on a bacterial plasmid pBR322. The size of the cloned segment was about Mr = 8.0 x 10(6). All of the genes for the four species of rRNA were linked on it, and there was a long spacer between the 5 S and 18-S rRNA coding regions. The nucleotide sequences of the regions flanking the 5-S rRNA gene were determined and compared with those in the corresponding regions of Sacharomyces cerevisiae [Valenzuela, P., Bell, G. I., Masiarz, F. R., DeGennaro, L. J., and Rutter, W. J. (1977) Nature, 267, 641-643; Maxam A. M., Tizard, R., Skryabin, K. G., and Gilbert, W. (1977) Nature, 267, 643-645]. The sequence of the T. utilis 5-S rRNA is identical with that of S. cerevisiae except for two residues at positions 18 and 61. However, its upstream region contained a quite different sequence, and a sequence which showed some homology was only found at positions -21 to -28. The sequences were d(T-G-T-A-A-C-C-T) in T. utilis and d(T-A-T-C-A-C-C-T) in S. cerevisiae. Although the presence of various repeat sequences having the same or opposite directions was noted, these repeats occurred at different positions in the two yeast species. In the downstream region, the common sequence was only seven dT deoxynucleotides, which occurred immediately after the 5-S rRNA coding sequence. Significant direct and inverted repeat sequences were found in T. utilis, but such repeats are not seen in S. cerevisiae. PMID- 6254758 TI - Identification of N,N-dimethylproline as the N-terminal blocking group of Crithidia oncopelti cytochrome c557. AB - The N-terminal tryptic peptide of Crithidia oncopelti cytochrome c557 X-Pro Me3Lys-Ala-Arg in which X represents an unknown N-terminal blocking group was characterized by electrophoresis at pH 2 and by 1H and 13C nuclear magnetic resonance. 1H-NMR spectra of the tryptic peptide suggested that the blocking group X was N,N-dimethylproline although the electrophoretic mobility of the peptide suggested a larger molecular weight. The peptides X-Pro-Me3Lys and X-Pro were generated by treatment of the tryptic peptide with thermolysin and carboxypeptidase and the free blocking group X was prepared by acid hydrolysis. Comparison of the 1H-NMR spectra of these peptides with spectra of synthetic N,N dimethylproline and N,N-dimethylprolylproline demonstrated that the blocking group was indeed N,N-dimethylproline. The 13C-NMR spectrum of the tryptic peptide was consistent with this conclusion although unambiguous assignments to all resonances could not be obtained because of the small amount of material available. The origin of the dimethylproline blocking group is discussed. PMID- 6254759 TI - The modification of the peptidyltransferase activity of 50-S ribosomal subunits, LiCl-split proteins and L16 ribosomal protein by pyridoxal phosphate. AB - Pyridoxal phosphate photoinactivates the peptidyltransferase activity of 50-S ribosomal subunits, LiCl split proteins and protein L16. Ethyromycin exhibits significant protection. These results, taken together with earlier reports, indicate the involvement of the single histidine of L16 in peptidyltransferase activity. The adjacent association in L16 of histidine and lysine indicates that pyridoxal phosphate should represent a selective inhibitor of peptidyltransferase activity. PMID- 6254760 TI - Cytochrome c interaction with yeast cytochrome b2. Heme distances determined by energy transfer in fluorescence resonance. AB - Fluorescent derivatives of cytochrome c were prepared by replacing the heme iron with closed-shell metals such as zinc or tin. The iron-free derivatives of cytochrome c bind to yeast lactate dehydrogenase (cytochrome b2) stoichiometrically and with high affinity. Spectral overlap exists between the fluorescence of porphyrin, Zn(II) or Sn(IV) cytochrome c and the absorption of the heme of cytochrome b; therefore dipole-dipole interaction is possible as predicted by Forster's theory of energy transfer. Changes in the fluorescence yield and the fluorescent decay profile of the cytochrome c derivatives are consistent with the view that the heme distance is sufficiently close for dipolar interactions. The distance calculated from the data depends upon assumptions in the theory for energy transfer and uncertainties in the experiment. It can be argued that due to the symmetry of the metalloporphyrins the relative orientations of the two hemes do not introduce a significant uncertainty in the calculation. However the decay profiles of the iron-free cytochromes are complex, possibly reflecting structural rearrangement of the polypeptide chain during the fluorescent lifetime. The steady-state fluorescent yields would indicate that the mean distance is around 1.8 nm. PMID- 6254761 TI - Proton nuclear-magnetic-resonance and resonance Raman studies of thermophilic cytochrome c-552 from Thermus thermophilus HB8. AB - The pH and temperature dependences of the 270-MHz proton nuclear magnetic resonance and resonance Raman spectra of Thermus thermophilus cytochrome c-552 were studied. Observation of the NMR methyl signal of the iron-bound methionine indicates that a methionine residue is the sixth ligand of heme iron in both ferric and ferrous states, although the environment of this methionine is not similar to that in mitochondrial cytochrome c. The NMR methyl signal of the coordinated methionine in the ferrous state was observed even at 87 degrees C, indicating the retention of the methionine ligand at the sixth coordination position. None of resonance Raman lines in ferrous cytochrome c-552 at higher temperatures showed a prominant temperature-dependent frequency shift, which implies that the heme iron was still bound with strong ligands and retained the low-spin state. In either redox state overall thermal denaturation did not occur even at 87 degrees C, although the ferric form existed in thermal spin mixture of the low-spin and high-spin species at higher temperatures. The hyperfine-shifted NMR resonances of the ferric form indicated rapid exchange of the sixth ligand at alkaline pH in the process of a single-step alkaline isomerization. PMID- 6254762 TI - Autoxidation of native oxymyoglobin. Thermodynamic analysis of the pH profile. AB - A complete kinetic description has been made on the pH profile for the autoxidation rate in terms of displacement of superoxide anion, O2- from MbO2 by the entering water molecule or hydroxyl ion. Using the equation, the effect of temperature on the autoxidation rate has been studied over the pH range 4.8-12.6 in 0.1 M buffer at 15 degrees, 25 degrees and 35 degrees C. The resulting thermodynamic parameters characterize the dissociation groups involved in the reaction as histidyl and tyrosyl residues. Despite the fact that each elementary process of the reaction is primarily protected against autoxidation by the high energy barrier of approximately 85-150 kJ . mol-1, the catalytic proton participates not only in decreasing the value of delta H degrees not equal to but also in increasing the value of delta S degrees not equal to to facilitate the formation of the activated complex, thereby promoting most of the autoxidation reaction of MbO2. The proton-catalyzed process is therefore of primary importance and a mechanistic detail of the reaction is discussed. PMID- 6254763 TI - Cation binding by the rat-incisor-dentine phosphoprotein. A spectroscopic investigation. AB - Nuclear magnetic resonance and electron paramagnetic resonance spectroscopy have been used to quantify metal binding to the phosphoprotein extractable from demineralized rat incisor dentine. Paramagnetic cation probes enable identification of the metal binding sites. Cations are able to diffuse across the protein surface while forming a relatively long-lived metal-phosphoprotein complex. The ability of the protein to sequester surface-mobile Ca(II) is discussed in terms of its ability to act as a possible nucleation site for the initial localization of Ca(II) within the dentine matrix. PMID- 6254764 TI - Sepharose 4B as a matrix for affinity chromatography. A spin-labelling investigation using nitroxides as model ligands. AB - Nitroxide spin labels were attached to CNBr-activated Sepharose 4B directly and through oligoglycines and oo-amino-carboxylic acids of varying length. The homogeneity of the carbohydrate environments of directly attached labels was investigated by measuring dipolar interactions between nitroxides as a function of solvation and of spin dilution with a diamagnetic analogue, as well as by electron exchange between the nitroxides and paramagnetic metal ions in solution. Only the exchange experiment revealed any inhomogeneity, suggesting that a small proportion of sites may be less accessible than the majority. The distances between sites were sufficiently small to allow, in principle, multiple-site interactions between quite small proteins in solution and immobilized ligands. Reorientation of the label at the matrix, characterized by the correlation time t, became more rapid with increasing spacer length n. For n > 12, the decrease in t was less pronounced. The two types of spacer behaved similarly. Thus an ideal spacer length for affinity separations is 12 atoms; this is in good agreement with data from a variety of affinity separations. The results of electron spin resonance studies of the effect of non-aqueous solvent on directly and indirectly labelled Sepharose 4B were used to suggest reasons why enzymes immobilized on Sepharose may be stabilized to denaturing solvents. PMID- 6254765 TI - Hydroxyl-ion-induced subunit dissociation of east cytoplasmic pyruvate decarboxylase. A circular dichroism study. AB - Cytoplasmic pyruvate decarboxylase (EC 4.1.1.1, from Saccharomyces carlsbergensis) exhibits in its circular dichroic spectrum in the 250--320-nm range a multiple two-signal band. This couplet disappears on increasing the pH up to pH 8.5. Two classes of two protons each can be quantified by these spectral changes. The first class dissociates rapidly and the apparent pK is 7.84. The thermodynamic data are delta G = 87.7 kJ mol-1, delta H = + 56.0 kJ mol-1, delta S = - 108 J mol-1 K-1, very characteristic for the deprotonation of an amino-acid side chain. The second class of the protons has the following thermodynamic data: delta G = 88.3 kJ mol-1, delta H = - 64.3 kJ mol-1, delta S = - 520 J mol-1 K-1 which, in conjunction with kinetic reasoning and in view of enzyme stoichiometry and symmetry, suggests a conformational equilibrium exposing the second two protons. Th enzyme dissociates into two dimeric subunits. This dissociation step is considered to be rate-determining for the overall process. The data are kp = 1.4 . 10(-3), delta H not equal to = + 128.3 kJ mol-1, delta S not equal = + 136 J mol-1 K-1. If there is a conformational equilibrium, the rate constant of product formation kp will be modified by a factor beta = kc/(1 + Kc) (0 < beta less than or equal to 1) where Kc is the conformational equilibrium constant. The subunit dissociation appears to be controlled by the enthalpy of activation indicating that a number of interactions, i.e. ionic, hydrogen and hydrophobic bridges, are to be broken. Optimal conditions for the preparation of the apo enzyme are derived from the data. PMID- 6254766 TI - Dissociation of the DNAse-I . actin complex by formamide. AB - Rabbit skeletal muscle actin labeled with 125 iodine by an enzymic method is shown to be capable of polymerization and to bind to matrix-bound pancreatic DNAse I like unlabeled G-actin. It was used to demonstrate that actin can be released from DNAse-I-agarose by 35--40% formamide. Actin which was only shortly exposed to this solvent was able to bind again to DNAse I and to form filaments indicating that it has been recovered functionally intact from the affinity matrix. PMID- 6254767 TI - Isolation of polymerization-competent cytoplasmic actin by affinity chromatography on immobilized DNAse I using formamide as eluant. AB - Formamide dissociates the G-actin . DNAse-I complex and is therefore suitable as an alternative to the eluant containing 3 M guanidinium hydrochloride, suggested originally by Lazarides and Lindberg [Proc, Natl Acad. Sci. USA, 71, 4742--4746 (1974)], to elute actin from immobilized DNAse-I agarose. Formamide provides the advantage of being a much weaker denaturant than guanidinium hydrochloride and being a nonionic substance. In the concentration necessary for the dissociation of the G-actin . DNAse-I complex (approximately 10 M) formamide denatures actin only slowly (half-time approximately 150 min at 2 degrees C) and thus allows the recovery of a large fraction of actin in a polymerization-competent form from the affinity column. Based on these findings a rapid two-step procedure for the isolation of non-muscle G-actin from cultured cells is described. The actin obtained in high yield and purity (greater than 90%) and can readily polymerize to F-actin. PMID- 6254768 TI - Respiratory properties of cytochrome-c-deficient mutants of Azotobacter vinelandii. AB - Cytochrome-c-deficient mutants of Azotobacter vinelandii have been isolated following mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine. These mutants grow well under nitrogen-fixing conditions and studies of the physiology and energy conservation efficiency show no apparent differences from those of the parent strain. Under oxygen-limited growth conditions, the growth rate of the cytochrome-c-deficient mutant was slightly slower (approx. 15%) than that of the parent strain. Cytochromes of the c-type are required for the oxidation of artificial electron donors such as reduced N,N,N',N'-tetramethyl-p phenylenediamine [Ph(NMe2)2]. This study could not demonstrate a physiological role for the c-type cytochromes which supports the idea that the minor Ph(NMe2)2 oxidizing pathway of the electron transport chain may be independent of the major pathway terminated by cytochrome d. PMID- 6254769 TI - Perchlorate binding to cytochrome c: a magnetic and optical study. AB - 1. The effects of perchlorate on cytochrome c have been investigated by 1H and 35Cl NMR, electron paramagnetic resonance and optical spectroscopy. 2. The pK values for the formation and disappearance of the major alkaline conformation were found to be displaced from 9.3 to 8.3 and from 10.4 to 10.9, respectively. The displacement was dependent on the ClO4(-) concentration below 0.1 M. 3. Competition experiments between perchlorate and chloride show that ClO4(-) binds both to the neutral and alkaline forms but with a higher affinity for the latter. The appearance of a new binding site in the alkaline form accounts for the markedly enhanced relaxation rate of 35ClO4(-) in this pH range. Complex formation between cyanide and the alkaline species results in the loss of this binding site, which probably is located close to or within the heme crevice. 4. The neutral form of ferricytochrome c also binds perchlorate strongly as evidence by the unique appearance of a high-spin signal dependent on pH and perchlorate concentration. This signal disappears with the same pK value as the neutral form. The effects of perchlorate on cytochrome c are due to specific binding of this ion. PMID- 6254770 TI - Purification and properties of the major apurinic/apyrimidinic endodeoxyribonuclease of rat-liver chromatin. AB - Two nucleases active on alkylated-depurinated DNA have been extracted from rat liver chromatin with 1 M KCl. The major enzyme was purified to near homogeneity; it has a molecular weight of 12 500 (although some dimerization might occur), needs Mg2+ or Mn2+ for activity. The endonuclease activity is specific for apurinic/apyrimidinic sites in DNA; the enzyme has no associated exonuclease activity. PMID- 6254771 TI - Determination of the stability constants of Mn2+ and Mg2+ complexes of the components of the NADP-linked isocitrate dehydrogenase reaction by electron spin resonance. AB - 1. The stability constants (Ks) of Mn2+ and Mg2+ complexes of isocitrate, 2 oxoglutarate, NADP and NADPH have been estimated by using electron spin resonance to measure free Mn2+ in ligand--metal-ion solutions. 2. The values of Ks for the Mn2+ complexes at 25 degrees C, in triethanolamine buffer containing NaCl, pH 7.0 and ionic strength 0.15 M, are 497 M-1 for isocitrate, 39 M-1 for 2 oxoglutarate, 467 M-1 for NADP and 943 M-1 for NADPH. 3. For the Mg2+ complexes under the same conditions, the Ks values are 357 M-1, 25 M-1, 133 M-1 and 179 M-1 respectively. The large difference between the stabilities of the isocitrate and 2-oxoglutarate complexes is thus largely responsible for the observed variation of the apparent equilibrium constant of the NADP-linked isocitrate dehydrogenase reaction with magnesium ion concentration. 4. NADP-linked isocitrate dehydrogenase from bovine heart mitochondria binds Mn2+, and the stability constant of the complex is about 2.2 x 10(4) M-1. The formation of this complex may explain the inhibition of the enzyme-catalysed reaction observed with Mn2+ concentrations greater than 0.2 mM in initial rate measurements. PMID- 6254772 TI - Organization of alpha-globin genes and mRNA translation in subjects carrying haemoglobin Hasharon (alpha 47 Asp replaced by His) from the Ferrara Region (Northern Italy). AB - In subjects carrying the haemoglobin Hasharon mutation (alpha 47 replaced by His), originally from the delta of the Po river (Northern Italy), the concentration of the alpha-globin variant has been evaluated and found to be approximately 32%, a value definitely higher than that reported for the same mutant haemoglobin in other regions. Restriction enzyme analysis has been carried out on the DNA from these subjects; the data obtained indicate the presence of three alpha-globin genes per diploid cell. Family studies further show that the two normal genes are located on one chromosome and the Hasharon gene on the other. The origin of the single alpha-gene in the Hasharon-carrying subjects of the Ferrara region is discussed in connection with their haematological and biosynthetic data. PMID- 6254773 TI - Purification and properties of a DNase inhibitor from Nicotiana tabacum cell cultures. AB - Extraction of Nicotiana tabacum cell cultures, chromatography on DEAE-cellulose and gel filtration resulted in a homogeneous protein (Mr = 14500), which strongly reduces the hydrolysis of Escherichia coli DNA by DNase I. DNA degradation by micrococcal nuclease is not inhibited. The inhibitor protein interacts with DNase I in the absence of DNA, as determined by the partial quenching of protein intrinsic fluorescence; a 1:1 stoichiometry is deduced. From the reduction of DNase I activity with increasing inhibitor concentration apparent equilibrium constants for the inhibitor X DNase-I complex have been calculated. This interaction is strongly temperature-dependent; at 20 degrees C and 26 degrees C dissociation constants of 5 nM and 110 nM, respectively, were determined. As a consequence a rather high enthalpy of interaction can be estimated. PMID- 6254774 TI - Purification and subunit structure of rat-liver phosphoprotein phosphatase, whose molecular weight is 260000 by gel filtration (phosphatase IB). AB - 1. Phosphoprotein phosphatase IB is a form of rat liver phosphoprotein phosphatase, distinguished from the previously studied phosphoprotein phosphatase II [Tamura et al. (1980) Eur. J. Biochem. 104, 347-355] by earlier elution from DEAE-cellulose, by higher molecular weight on gel filtration (260000) and by lower activity toward phosphorylase alpha. This enzyme was purified to apparent homogeneity by chromatography on DEAE-cellulose, aminohexyl--Sepharose-4B, histone--Sepharose-4B, protamine--Sepharose-4B and Sephadex G-200. 2. The molecular weight of purified phosphatase IB was 260000 by gel filtration and 185000 from S20,W and Stokes' radius. Using histone phosphatase activity as the reference for comparison, the phosphorylase phosphatase activity of purified phosphatase IB was only one-fifth that of phosphatase II. 3. Sodium dodecyl sulfate gel electrophoresis revealed that phosphatase IB contains three types of subunit, namely alpha, beta and gamma, whose molecular weights are 35000, 69000 and 58000, respectively. The alpha subunit is identical to the alpha subunit of phosphatase II. While the beta subunit is also identical or similar to the beta subunit of phoshatase II, the gamma subunit appears to be unique to phosphatase IB. 4. When purified phosphatase IB was treated with 2-mercaptoethanol at -20 degrees C, the enzyme was dissociated to release the catalytically active alpha subunit. Along with this dissociation, there was a 7.4-fold increase in phosphorylase phosphatase activity; but histone phosphatase activity increased only 1.6-fold. The possible functions of the gamma subunit are discussed in relation to this activation of enzyme. PMID- 6254775 TI - Size of vasopressin receptors from rat liver and kidney. AB - Specific vasopressin receptors in rat liver membranes were recently characterized [Cantau et al., Journal of Receptors Research, in the press]. They differ from the receptors characterized earlier in kidney membranes as regards coupling with adenylate cyclase and specificity towards vasopressin structural analogues [Rajerison et al. (1974) J. Biol. Chem. 249, 6390-6400; Butlen et al. (1978) Mol. Pharmacol. 14, 1006-1017]. The object of the present work was to see whether these differences reflect a difference in the molecular size of liver and kidney vasopresin receptors. For this purpose, rat liver and kidney membranes were incubated with [3H]vasopressin and solubilized with Triton X-100 (0.3%). The properties of the macromolecular components of soluble extracts to which labelled vasopressin remained bound were observed to resemble those of the intact membrane receptors as regards binding reversibility at 30-37 degrees C and sensitivity to guanyl nucleotides. The hydrodynamic parameters of the soluble hormone-receptor complexes were estimated from Utrogel column filtration experiments and from sucrose density gradient ultracentrifugation experiments. The following values were obtained for liver and kidney receptors respectively: Stokes' radii: 5.4 and 5.6 nm; standard sedimentation coefficients: 3.7 and 3.7 S; partial specific volumes: 0.75 and 0.78 ml x g-1; molecular weight: 83000 and 80000. These results indicate that the marked functional differences between liver and kidney receptors are not accompanied by appreciable differences in molecular size. PMID- 6254776 TI - Elevated CSF cyclic AMP concentrations in patients with inflammatory diseases of cerebral and extracerebral origin. AB - Cyclic 3'-5' adenosine monophosphate (c-AMP) concentrations were measured in cerebrospinal fluid (CSF) from children admitted to the hospital because of suspected meningitis. c-AMP levels were found to be markedly elevated (P < 0.001) during the acute phase of most of the purulent meningitis patients, as well as in patients with acute aseptic meningitis. In convalescent patients after purulent meningitis mean c-AMP concentrations remained elevated (P < 0.01) beyond the normalization of the routine parameters in CSF. In addition, a variety of febrile inflammatory conditions of extracerebral origin produced elevations (P < 0.001) of c-AMP although CSF by routine criteria was normal. The results suggest that c AMP might serve as a sensitive indicator of transient cellular metabolic disturbance in the brain. PMID- 6254777 TI - Changes of the rotavirus concentration in faeces during the course of acute gastroenteritis as determined by the immune adherence hemagglutination test. AB - Concentrations of rotavirus were studied in serially sampled faecal specimens from 55 patients with acute gastroenteritis, utilizing the immune adherence hemagglutination (IAHA) test. Rotavirus antigen was detected in 45 (82%) out of 55 cases. In the faeces which were positive for rotavirus antigen, the concentrations reached their maximum titer shortly after the onset of the illness and diminished gradually until the 9th day. PMID- 6254778 TI - Peripheral neuropathy due to gasoline sniffing - A case report. AB - A case of polyneuropathy in a 14-year-old boy, a chronic gasoline sniffer, is reported. Clinical and electromyographic examination showed a symmetrical motor involvement, mainly distally and in the lower limbs. A sural nerve biopsy showed only slight changes, both of axonal and demyelinating type. The role of gasoline toxic substances in the etiology of this rare polyneuropathy is discussed. PMID- 6254779 TI - Diagnostic capacity of sinus node recovery time after inhibition of autonomous neural tone. AB - Symptomatic arrhythmias often occur intermittently in patients with sinus node dysfunction. A diagnostic test with ability to reveal latent sinus disease has therefore been much sought for. Determinations of sinus node recovery time (SNRT) and corrected sinus node recovery time (CSNRT) have been attempted but limitations in their diagnostic power are well recognized. To eliminate a possible masking effect of autonomous neural tone, propranolol 0.1 mg/kg and atropine 0.02 mg/kg was administered to 30 patients with established symptomatic sinus bradydysrhythmias (SSBD) and to a control group of 18 age-matched healthy volunteers. In addition the same procedure was applied to 9 patients with symptoms suggesting SSBD in whom, however, this cause was later excluded. The upper normal limit of CSNRT defined by the control group was 545 msec before and 505 msec after drugs. In the SSBD group, CSNRT was falsely negative in 8 of the 30 patients. Repeated testing after drug inhibition reduced this number to 2 patients. Thus, the sensitivity increased from 73% to 93%. CSNRT determinations were normal in the non-SSBD patients, specificity remaining at 100%. Thus, the discriminative power of electrophysiologic testing for sinus node disease was found to be high when CSNRT determinations were performed both before and after drug inhibition of autonomous neural tone. PMID- 6254780 TI - Adrenergic control of human adipose tissue lipolysis. PMID- 6254781 TI - Inhibition of human fat cell adenylate cyclase mediated via alpha-adrenoceptors. AB - Human adipose tissue contains alpha- as well as beta-adrenoceptor sites mediating antagonistic catecholamine effects on lipolysis. To characterize the mechanisms of catecholamine action in biochemical terms we have studied the effects of the almost pure beta-adrenoceptor agonist isoproterenol and of the mixed adrenergic agonist adrenaline on human fat cell adenylate cyclase in the presence of alpha- and beta-adrenoceptor blocking drugs. In contrast to the almost pure beta adrenergic agent isoproterenol, the mixed agonist adrenaline, besides its stimulatory action, also had inhibitory effects which became apparent upon complete beta-adrenoceptor blockade using 0.05 mmol/l propranolol. Under these conditions adrenaline caused a dose-dependent inhibition of basal and parathyroid hormone-activated enzymic activity with a maximum of 30-50%, which was dependent on GTP and could be reversed by simultaneous alpha-adrenergic blockade using 5 mumol/l dihydroergotamine or 10 mumol/l phentolamine. These results support the concept of antogonistic alpha- and beta-adrenoceptor sites coexisting as regulatory subunits of the human fat cell adenylate cyclase. PMID- 6254782 TI - Inhibition of growth in young mice treated with pentazocine: reversal by naltrexone. AB - One week old mice were injected subcutaneously once daily with d,1-methadone (5 mg/kg), pentazocine, naltrexone, naloxone, nalorphine or nalbuphine, each at 10 mg/kg. The remaining half of each litter was used as control. Only methadone and pentazocine groups showed reduced weight gain after 3 weeks of treatment (P < 0.01). Injection of pentazocine in dosages of 5-20 mg/kg inhibited weight gain and protein synthesis in a dose-related manner. The incorporation of labeled leucine was followed in brain, liver and muscles. Methadone and pentazocine groups showed a significant decrease in protein synthesis in all tissues studied. The nalbuphine, nalorphine, naloxone, and naltrexone-treated groups incorporated leucine normally, correlating with normal weight gain. These data suggest that pentazocine, unlike the other mixed agonist-antagonists and antagonists, adversely affects the growth of very young animals when administered chronically. A specific opioid effect is suggested by the fact that naltrexone given concomitantly with the pentazocine prevents development of the biochemical lesion. PMID- 6254783 TI - The in situ blood perfused rat mesentery; a model for assessing modulation of adrenergic neurotransmission. AB - The present study describes a method for the in situ blood perfusion of the rat mesentery and compares this method with the in vitro method of McGregor. The in situ method gives stable baseline perfusion pressures for over 2 h and consistent vasoconstrictor responses to both periarterial nerve stimulation (NS) and exogenous norepinephrine (NE). The responses to NS are blocked by phentolamine and reserpine whereas the responses to NE are blocked by phentolamine but potentiated by reserpine. The threshold responses to NS and NE were 3 Hz and 100 ng, respectively, in the in situ preparation and 11 Hz and 200 ng, respectively, in the in vitro preparation. When the effects of prostaglandin E2 (PGE2) were examined in indomethacin-treated mesenteries, PGE2 decreased the responses to both NS and NE in the in situ preparation, but in the in vitro preparation, PGE2 enhanced the response to NS and NE. Thus, the in situ blood perfused rat mesentery is a stable and reproducible model for examining the effects of drugs and hormones on adrenergic neurotransmission and responses to exogenous norepinephrine. PMID- 6254785 TI - Displacement of [3H]clonidine binding by clonidine analogues in membranes from rat cerebral cortex. AB - [3H]Clonidine binds to membranes prepared from rat cerebral cortex by a high affinity saturable process. Using [3H]clonidine of specific activity 5.29 Ci/mmol the Kd for the binding was 1.7 +/- 0.1 nM and the Bmax 9.4 +/- 0.6 pmol/g (n = 5). The Hill coefficient for [3H]clonidine binding to rat cerebral cortex membranes was 0.97 +/- 0.05 (r > 0.93; n = 5) indicating an absence of +ve or -ve cooperativity. The clonidine metabolites 4-hydroxyclonidine; N(2,6 dichlorophenyl)guanidine; N(2,6-dichloro-4-hydroxyphenyl)guanidine; and 2-(2,6 dichlorophenyl)iminoimidazolidine-4-one and the metabolic intermediate 2-(2,6 dichlorophenylamino)imidazole were less effective displacers of [3H]clonidine binding than the parent compound. The first three compounds were more polar and the last two less polar than clonidine as judged by their apparent partition coefficients in octanol/phosphate buffer. Seven imidazolidine derivatives with known alpha-adrenoceptor activity were potent displacers of [3H]clonidine binding: the order of potency being 14,304-18 > naphazoline > clonidine > lofexidine and tiamenidine > CP18,534 > ST600 > ST91. Five 'clonidine-like' drugs displaced [3H]clonidine binding with an order of potency guanabenz > Baya 6781 > guanfacine > clonidine > xylazine >> FLA136. Apparent partition coefficients of the displacing agents have been measured in octanol/phosphate buffer and the importance of this factor is discussed with reference to their in vivo antihypertensive potency and potency as displacers of [3H]-clonidine binding. PMID- 6254786 TI - Angiotensin converting enzyme. V. Serum levels as monitors of disease activity in corticosteroid-treated sarcoidosis. AB - Serum angiotensin-converting enzyme (ACE) activity was related to clinical markers of disease activity, mainly chest X-rays, pulmonary function tests and serum lysozyme (LZM) in 41 sarcoidosis patients, who received corticosteroid treatment. Increased ACE activity before treatment predicted improvement of diffusion capacity during treatment, whereas chest X-rays improved regardless of the initial ACE value. ACE decreased after initiation of treatment both in sarcoidosis patients and in healthy volunteers. In sarcoidosis most decreases were parallelled by similar LZM changes, which did not occur in volunteers. When an apparently stable state had been achieved, ACE was no longer a reliable monitor of disease activity. It often fluctuated within normal limits without accompanying clinical or LZM changes. It was not dose-dependent during daily medication but increased during alternate day administration. This may reflect decreased suppression of ACE by steroids but may also indicate reactivation of the disease process. Elevated ACE values after cessation of treatment preceded or parallelled a relapse. LZM values did not add to the information provided by ACE measurements before, during or after treatment. PMID- 6254784 TI - Hypersensitivity of cardiac beta-adrenergic receptors after neonatal treatment of rats with 6-hydroxydopa. AB - The cardiac beta-adrenergic response to noradrenaline (NA) was investigated in the rat neonatally s.c. treated with 6-hydroxydopa (6-OHDOPA, 75 mg/kg, 0, 2 and 4 days after birth). 6-OHDOPA treatment significantly (P < 0.05) reduced the NA content by 32% of the control in whole heart and markedly potentiated the isoproterenol (0.17 mg/kg, i.p.)-induced stimulation of ornithine decarboxylase activity which had been blocked by a preceding i.p. injection of propranol (10 mg/kg) at the adult stage. Scatchard analysis of the specific [3H] dihydroalprenolol ([3H]DHA0 binding indicated that 6-OHDOPA induced an increase in the maximum number of specific binding sites of [3H]DHA but did not alter the dissociation constant. In addition, 6-OHDOPA treatment resulted in a potentiation of the positive inotropic response to NA but not to isoproterenol in isolated atria. It is suggested that 6-OHDOPA treatment produces an increased density of beta-adrenergic receptor sites relevant to the hypersensitivity of beta-receptors to NA. PMID- 6254787 TI - Pleural granulocytes with cytoplasmic inclusions from patients with malignant lung tumours and mesothelioma. AB - Granulocytes with cytoplasmic inclusions (RA = Rheumatoid Arthritis cells) have previously been found in pleural effusions of rheumatoid and tuberculous origin. We now report the finding of RA-cells in effusions from patients suffering from bronchogenic carcinomas of the squamous-cell type and malignant mesothelioma. Such cells occurred only rarely in other types of primary or secondary lung tumour. PMID- 6254788 TI - Approaches to the understanding of mechanisms in occupational asthma. PMID- 6254789 TI - Theophylline actions on adenosine receptors. PMID- 6254790 TI - Transient changes in the size of the extracellular space in the sensorimotor cortex of cats in relation to stimulus-induced changes in potassium concentration. AB - The time course of local changes of the extracellular space (ES) was investigated by measuring concentration changes of repeatedly injected tetramethylammonium (TMA+) and choline (Ch+) ions for which cell membranes are largely impermeable. After stimulus-induced extracellular [K+] elevations the delta [TMA+] and delta [Ch+] signals recorded with nominally K+-selective liquid ion-exchanger microelectrodes increased by up to 100%, thus indicating a reduction of the ES down to one half of its initial size. The shrinkage was maximal at sites where the K+ release into the ES was also largest. At very superficial and deep layers, however, considerable increases in extracellular K+ concentration were not accompanied by significant reductions in the ES. These findings can be explained as a consequence of K+ movement through spatially extended cell structures. Calculations based on a model combining the spatial buffer mechanism of Kuffler and Nicholls (1966) to osmolarity changes caused by selective K+ transport through primarily K+ permeable membranes support this concept. Following stimulation additional iontophoretically induced [K+]0 rises were reduced in amplitude by up to 35%, even at sites where maximal decreases of the ES were observed. This emphasizes the importance of active uptake for K+ clearance out of the ES. PMID- 6254791 TI - Hyperpolarization of hypothalamic parvocellular neurons by 17 beta-estradiol and their identification through intracellular staining with procion yellow. AB - Intracellular recordings and injections of procion yellow (PY) were made in parvocellular neurons in hypothalamic slices of female guinea pigs. Eighty-five neurons, with an average resting membrane potential of -35 mV, were recorded in the arcuate (ARC) ventromedial (VM), and in the cell-poor zones between the ARC and VM. Eleven of the ARC neurons and four neurons from the cell-poor zone could be driven antidromically by median eminence (ME) stimulation, nine other neurons from the three areas could be driven orthodromically by stria terminalis (ST) stimulation. Twenty-eight parvocellular neurons were tested with 17 beta estradiol (E2), which was applied in the bathing medium as the free steroid. Eleven neurons (nine ARC and two cell-poor-zone neurons) were hyperpolarized 2 to 24 mV by 10(-10) M E2 concentrations. 10(-8) M estrone concentration was without effect on three of these cells. Through the intracellular injection of PY, the estrogen-sensitive neurons (N = 11) were identified as small fusiform cells with few dendrites. Spine-like appendages were found on only one of these cells. None of the larger pyramidal-like neurons of these areas responded to the application of E2. PMID- 6254792 TI - Glucose oxidation in the ventromedial hypothalamus is not affected by insulin or ouabain but depressed by alloxan treatment. AB - Insulin is apparently not required for VMH glucose oxidation in vitro. Ouabain, an inhibitor of the Na-K pump ATPase, does not prevent VMH glucose oxidation in vitro. These data suggest (a) the VMH does not exhibit a cotransport phenomenon of glucose with the Na-K pump mechanism, and (b) glucose oxidation in the VMH is not insulin dependent. Alloxan-diabetes was induced to increase tissue insulin sensitivity. A comparison of glucose oxidation rates in alloxan-diabetic VMH tissue and normal VMH tissue, supplemented only with saline, indicated a highly significant (p < 0.001) depression of glucose oxidation in the alloxan-treated tissue. Cell membranes in the VMH are perhaps altered by alloxan. PMID- 6254793 TI - Cholinergic transmission regulates extrajunctional acetylcholine receptors. PMID- 6254794 TI - Developmental changes in posttetanic potentiation of muscular potentials in the rat. PMID- 6254795 TI - Regional cyclic AMP levels in homogenates of rat brain after ketalar and trifluoperazine. AB - There was a significant fall in cAMP levels after administration of TFP or ketalar. Different amounts of cAMP were present in different regions of rat brain. Concentrations of cAMP in different regions of the rat brain were found to decrease in the following order: cerebrum > thalamus with hypothalamus > midbrain > hippocampus > cerebral cortex. PMID- 6254796 TI - Conversion of mammalian cyclic GMP-dependent protein kinase into modulator dependent protein kinase (type II) in vitro. AB - The spontaneous conversion of mammalian cyclic GMP-dependent protein kinase (G PK) into modulator-dependent protein kinase (type II) (M-PKII) in the absence of cGMP or histone was observed in vitro. The findings, together with similarity in substrate protein specificity, suggest that M-PKII is the catalytic subunit of mammalian G-PK. PMID- 6254797 TI - Separation of modulator-dependent protein kinase (type I) from cyclic GMP dependent protein kinase in mouse testes. AB - A new type of enzyme, modulator-dependent protein kinase (type I) (M-PKI), was successfully isolated from the cytosol fraction of mouse testes. It was eluted slightly after the peak of cyclic GMP-dependent protein kinase (G-PK) by Sephadex G-200 gel filtration. Unlike either cyclic AMP-dependent protein Kinase (A-PK) or G-PK, its maximal activity depended exclusively on the presence of crude protein kinase modulators (PKM) or partially purified stimulatory modulator (PKMs). PMID- 6254798 TI - Evidence against the involvement of cyclic GMP in the insulin-stimulation of lipoprotein lipase activity in fat cells. AB - Under in vitro experimental conditions in which insulin increases adipose tissue lipoprotein lipase, cyclic GMP or dibutyryl cyclic GMP has no effect on this enzyme in rat adipose tissue fragments, or on either the intra- or extracellular forms of this enzyme in isolated fat cells. These results do not support the involvement of cyclic GMP in the insulin-stimulation of lipoprotein lipase in adipose tissue. PMID- 6254799 TI - Modification of radiation response by agents that elevate the intracellular c-AMP level. AB - A study has been made of the effects of drugs known to elevate c-AMP level on radiation-induced damage in thymocytes. The test used was the ability of the cells to exclude dye, beta-receptor stimulation and phosphodiesterase inhibition were found to induce radioresistance. The possible importance of the plasma membrane in connection with cytoplasmic factors is briefly discussed. PMID- 6254800 TI - Physical exercise stimulates marked concomitant release of beta-endorphin and adrenocorticotropic hormone (ACTH) in peripheral blood in man. AB - ACTH and beta-endorphin have been evaluated by means of a specific and sensitive radioimmunoassay in athletes reaching a status of physical stress. A concomitant marked increase of these 2 peptides has been recorded. The implications of this finding lead to the conclusion that stress stimulates the synthesis of the common precursor (31 K) in the pituitary. PMID- 6254801 TI - Prospects for improved contraception. AB - Some important new birth control methods have been developed in the postpill, post-IUD era; others are on the way. But shrinking dollars in research (especially R&D), inadequate coordination and planning by donors and programs, and costly and complex regulatory requirements frustrate efforts to use current knowledge to make major breakthroughs. PMID- 6254802 TI - [Pharmacological analysis of the cardiac stimulating action of mezaton]. AB - In anesthetized dogs and rabbits, the increasing doses of mesaton raise the cardiac output and diminish overall peripheral vascular resistance. The cardiostimulant effect is prevented by obsidan, whilst the negative chronotropic by atropine. The effect of mesaton on alpha- and beta-adrenoreceptors is discussed. PMID- 6254803 TI - Ligand-induced changes at the hepatocyte sinusoidal plasma membrane. PMID- 6254804 TI - Proteolytic cleavage of exotoxin A from Pseudomonas aeruginosa: formation of an ADP-ribosyltransferase active fragment by the action of Pseudomonas elastase. PMID- 6254805 TI - Calcium uptake by reconstituted vesicles is mediated by a chymotrypsin-sensitive peptide associated with cytochrome oxidase. PMID- 6254806 TI - Specific labelling of platelet membrane glycoproteins. PMID- 6254807 TI - Increased effect of adrenaline on cyclic AMP formation and positive beta adrenergic modulation of DNA-synthesis in regenerating hepatocytes. PMID- 6254808 TI - Affinity chromatography purification of cytochrome c oxidase: use of a yeast cytochrome c - thiol-Sepharose 4B column. PMID- 6254810 TI - GABA induces behavioral and developmental metamorphosis in planktonic molluscan larvae. AB - Swimming planktonic larvae of the marine gastropod mollusc Haliotis rufescens require exogenous GABA or its homologs for induction of their genetically programed behavioral and developmental metamorphosis to the adult form. This requirement is stereochemically specific and absolute; GABA at 10(-6) M is fully effective in the induction of cellular differentiation, proliferation and organogenesis. The kinetics of the development of larval competence for GABA induction, and of the early metamorphic processes induced by GABA, are described. Biochemical, histological and electron micrographic analyses suggest that cyclic AMP, calcium, and a glycopeptide secretion from the cephalic sensory complex may mediate transduction of the GABA signal in the control of behavioral and morphogenetic changes induced by this environmentally deployed transmitter substance. This first observation and characterization of a major role for GABA in the control of differentiation and development, and the experimentally tractable system in which these are demonstrated, are of significance for further biomedical research. PMID- 6254809 TI - Identification of an AMP-activatable pyruvate dehydrogenase isozyme in embryos and tumors. PMID- 6254811 TI - [Review: mechanisms of adaptation of the cardiovascular system to hypoxic conditions]. PMID- 6254812 TI - [Fluctuations in the structure of background spiking of cortical neurons following noradrenaline application]. PMID- 6254813 TI - [Effect of different doses of ACTH fragments on the bodies of white rats]. AB - ACTH fragments improved the establishing of food--rewarded behaviour in white rats. The effective dose of ACTH4-7 (0.05 mg/kg) was higher as compared to that of ACTH4-10 (0.015 mg/kg). The further increase in the dose of the peptides induced no enhancement of their behavioral effect but produced general excitation of the rats (increase in their motor activity, O2 consumption, heart rate). The peptides seem to produce a direct effect on the mechanisms of learning, which is independent of their general excitatory action. PMID- 6254814 TI - [Antagonism between tetrodotoxin and hydrocortisone in their effects on the intensity of glycolysis in rat hippocampus]. PMID- 6254815 TI - [Relationship between synaptic facilitation and the potassium component of endplate currents]. PMID- 6254816 TI - [Variation of the method for studying miniature endplate currents in frogs]. PMID- 6254817 TI - Presence of antibodies to the viral proteins in sera of mammals bearing RSV induced tumours. AB - The sera of RSV tumour-bearing rats, hamsters and monkeys were tested for the presence of antibodies to RSV proteins. Complement fixation test and radioimmunoprecipitation followed by SDS-polyacrylamide gel electrophoresis were used for detection of antibodies to the products of the gag, env and src genes of RSV. Antibodies to the env and gag gene products were found in sera of tumour bearing monkeys. Hamster sera contained antibodies to the gag gene products only. No antibodies were detected in sera of tumour-bearing rats. The differences in immunogenicity of RSV gene products in various hosts are discussed. PMID- 6254818 TI - Adenoid cystic carcinoma of minor salivary glands. PMID- 6254819 TI - Flow cytometry: a novel approach for the quantitative analysis of receptor- ligand interactions on surfaces of living cells. PMID- 6254820 TI - Modulation of cyclic AMP content of the rat myometrium: desensitization to isoproterenol, PGE2 and prostacyclin. AB - Exposure of the oestrogen-dominated rat myometrium to either isoproterenol or PGE2 resulted in a rapid but transient accumulation of cyclic AMP, with a progressive loss of responsiveness to the corresponding agonist. Induction of refractoriness was a time- and dose-related phenomenon. In the earliest time, desensitization was agonist-specific but was followed, with continued exposure, by a cross desensitization between isoproterenol and PGE2 and vice versa. Differential time courses for development and reversal of specific and heterologous refractoriness indicate at least 2 different processes for the 2 phenomena, the non-specific type being possibly mediated by cyclic AMP. Exposure to isoproterenol or PGE2 also caused an attenuated cyclic AMP response to prostacyclin (PGI2). Kinetics for PGE2-induced desensitization to PGI2 were comparable to that of an agonist-specific refractoriness, indicating that PGE2 and PGI2 may share common receptor sites. PGF2 alpha, PGD2 and 6-keto PGF1 alpha, which contract the myometrium but are ineffective on adenylate-cyclase activity, did not promote cyclic AMP refractoriness to PGE2, PGI2 or isoproterenol. Isoproterenol also caused refractoriness to its own relaxing activity, whereas PGE2 did not affect isoproterenol-induced relaxation despite a marked attenuation of the beta-adrenergic response to cyclic AMP. These results provide further evidence for the non-exclusive role of cyclic AMP in mediating uterine relaxation. PMID- 6254821 TI - Evidence that glycosylation of pro-opiocortin and ACTH influences their proteolysis by trypsin and blood proteases. AB - The role of the carbohydrate in the stabilizaion and protection of the glycoprotein, pro-opiocortin, from non-specific proteolysis by trypsin and blood proteases was studied in vitro. [3H]Arginine-labeled, glycosylated and non glycosylated forms of pro-opiocortin were isolated from frog neurointermediate lobes and subjected to proteolysis by trypsin. The non-glycosylated form was degraded by trypsin more rapidly than the glycosylated form. Analysis of the tryptic products after trypsin treatment, showed that the non-glycosylated pro opiocortin was cleaved to unidentified peptides within 1 min, whereas the glycosylated prohormone yielded 2 products, mol. wt. 23 000 ACTH and mol. wt. 21 000 ACTH, synthesized by the intact neurointermediate lobe. These data provide direct evidence in support of the hypothesis, derived from studies on the intact lobe (Loh and Gainer, 1978, 1979) that the glycosylation of pro-opiocortin is important: (1) to protect it against non-specific proteolysis in situ, and (2) to direct processing by limiting proteolysis. In addition, we demonstrate that glycosylated forms of ACTH are much more stable in blood than non-glycosylated forms. PMID- 6254822 TI - Human choriogonadotropin-induced desensitization of granulosa-cell adenylate cyclase to gonadotropins and loss of LH/hCG receptor. AB - Immature female rats that had been primed with pregnant-mare serum gonadotropin (PMSG) were injected intravenously with various doses of human choriogonadotropin (hCG) for the investigation of the relationship between adenylate cyclase activities and the concentrations of LH/hCG receptor in luteinizing granulosa cells. Injection of 1 microgram of hCG induced a loss of LH and FSH sensitivities of adenylate cyclase within 6 h and a disappearance of free LH/hCG receptors within 24 h. Basal adenylate cyclase activity has a transient maximum at 6 h after hCG injection. After injection of 100 micrograms of hCG the loss of LH sensitivity of adenylate cyclase and free LH/hCG receptors occurred immediately, but the changes in FSH-stimulated and basal activities followed the same time scale as after injection of 1 microgram of hCG. When hCG was omitted from the injections the response of the animals to the endogenous gonadotropin surge varied. A complete desensitization of adenylate cyclase to LH and FSH stimulation and a 65% loss of free LH/hCG receptors were found at 24 h if the follicles were ovulated. These results suggest that occupation of a limited number of LH/hCG receptors in granulosa cells induces adenylate cyclase refractory to further stimulation by gonadotropins. The transient elevation of basal adenylate cyclase activity and its desensitization to further stimulation by gonadotropins may have a role in physiological processes leading to ovulation and luteinization. PMID- 6254823 TI - Receptor stability and channel conversion in the subsynaptic membrane of the developing mammalian neuromuscular junction. PMID- 6254824 TI - Electron microscopic studies of chimeric blastocysts experimentally produced by aggregating blastomeres of rat and mouse embryos. PMID- 6254825 TI - Studies on the insulin mediator. II. Separation of two antagonistic biologically active materials from fraction II. AB - Insulin treatment significantly altered the elution profile of deproteinized muscle extracts chromatographed on Sephadex G-25 columns, particularly in fraction II, which contains the insulin mediator. Further purification of fraction II by high-voltage paper electrophoresis at pH 1.9 and 3.5 resulted in two active fractions. Fraction 1 leads to 4 stimulated the cyclic AMP-dependent protein kinase and inhibited glycogen synthase phosphoprotein phosphatase, and may be a novel substance. Fractions 1 leads to 6 and 3 leads to 6 inhibited the cyclic AMP-dependent protein kinase and stimulated glycogen synthase phosphatase. It is proposed that the insulin mediator is present in fractions 1 leads to 6 and 3 leads to 6. PMID- 6254826 TI - [Influence of cortisol and the inhibitors of protein biosynthesis (puromycin) on the lipolytic activity, in vitro, of cyclic adenosine monophosphate]. PMID- 6254827 TI - [Evaluation of the dietary fiber ratio in the Midi-Pyrenee region and in New California]. PMID- 6254828 TI - [Increased hair growth during prolonged tocolytic therapy with fenoterol. Measurements of testosterone, androstandiol, cortisol and ACTH (author's transl)]. AB - 28 patients out of 30 treated with a longtime i.v. infusion of Fenoterol showed an intensive hair growth all-over the skin not especially showing the Linea alba and the beard. To investigate the normal hair growth during pregnancy we examined 384 volontiers just before delivery. 2,8% showed an android hair growth and 3,6% a more intensive hair growth all over the skin. To investigate the role of hormones in the excessive hair growth following i.v. tocolysis with Fenoterol, we measured Testosterone, 5 a-androstan-3 beta-17 beta-diol, Cortisol and ACTH. In contrast to the reports in literature we found a decrease in Testosterone during the treatment with Fenoterol. After an initial fall Androstandiol showed a slight rise in the 3rd week of therapy. ACTH and Cortisol remained unchanged. Contrary to the literature we did not see any augmentation of plasma Cortisol. We conclude, that androgen metabolites are not the reason for the intensive hair growth. The hair growth may be due to a more intensive metabolism within the hair follicle. PMID- 6254829 TI - [Endocrine regulation of the endometrium throughout the menstrual cycle (author's transl)]. PMID- 6254830 TI - Duplicated genes producing transposable controlling elements for the mating-type differentiation in Saccharomyces cerevisiae. AB - Mutation of the two homothallic genes, HML alpha/HMLa and HMRa/HMR alpha, in homothallic strains of Saccharomyces cerevisiae was studied. Of 11 mutants of the HML alpha gene, eight were due to a phenotypic mutation from HML alpha to HMLa, i.e., a mutation causing a change in function of the original HML allele to that of the other HML allele (functional mutation), and three were due to a defective mutation at the HML alpha gene, i.e., a mutation causing a nonfunctional allele (nonfunctional mutation). All 14 mutants of the HMRa gene, on the other hand, were due to a phenotypic mutation from HMRa to HMR alpha i.e., a functional mutation. Phenotypic reverse mutations, i.e., HMLa to HML alpha and HMR alpha to HMRa, were also observed in the cultivation of EMS (ethyl methanesulfonate) treated spores having the HO HMR alpha HMLa genotype. Mutation from heterothallic cells to homothallism was observed in a nonfunctional mutant of the HML alpha gene, by mutagenesis with EMS, but not in the functional mutants of the HML alpha and HMRa genes or in the authentic strains having the alpha HO HMR alpha HML alpha (alpha Hp) and a HO HMRa HMLa (a Hq) genotypes. These observations suggest that the functional mutation is not caused by the direct mutation from a homothallic allele to the opposite, but by replacement of a transposable genic element produced from a homothallic locus with a region of a different homothallic locus. These observations also support the controlling-element model and the cassette model, which have been proposed to explain the mating-type differentiation by the homothallic genes. PMID- 6254831 TI - Genes affecting the expression of cytochrome c in yeast: genetic mapping and genetic interactions. AB - The four mutant genes, cyc2, cyc3, cyc8 and cyc9, that affect the levels of the two iso-cytochromes c in the yeast Saccharomyces cerevisiae have been characterized and mapped. Both cyc2 and cyc3 lower the amount of iso-1-cytochrome c and iso-2-cytochrome c; whereas, cyc8 and cyc9 increase the amount of iso-2 cytochrome c. The cyc2, cyc3, cyc8 and cyc9 genes are located, respectively, on chromosomes XV, I, II and III, and are, therefore, unlinked to each other and unlinked to CYC1, the structural gene of iso-1-cytochrome c and to CYC7, the structural gene of iso-2-cytochrome c. While some cyc3 mutants are completely or almost completely deficient in cyotchromes c, none of the cyc2 mutants contained less than 10% of parental level of cytochrome c even though over one-half of the mutants contain UAA or UAG nonsense mutations. Thus, it appears as if a complete block of the cyc2 gene product still allows the formation of a residual fraction of cytochrome c. The cyc2 and cyc3 mutant genes cause deficiencies even in the presence of CYC7, cyc8 and cyc9, which normally cause overproduction of iso-2 cytochrome c. We suggest that cyc2 and cyc3 may be involved with the regulation or maturation of the iso-cytochromes c. In addition to having high levels of iso 2-cytochromes c, the cyc8 and cyc9 mutants are associated with flocculent cells and other abnormal phenotypes. The cyc9 mutant was shown to be allelic with the tup1 mutant and to share its properties, which include the ability to utilize exogenous dTMP, a characteristic flocculent morphology, the lack of sporulation of homozygous diploids and low frequency of mating and abnormally shaped cells of alpha strains. The diverse abnormalities suggest that cyc8 and cyc9 are not simple regulatory mutants controlling iso-2-cytochrome c. PMID- 6254832 TI - Dependence on mating type for the overproduction of iso-2-cytochrome c in the yeast mutant CYC7-H2. AB - The CYC7-H2 mutation causes an approximately 20-fold overproduction of iso-2 cytochrome c in a and alpha haploid strains of the yeast Saccharomyces cerevisiae due to an alteration in the nontranslated regulatory region that is presumably contiguous with the structural region. In this investigation, we demonstrated that heterozygosity at the mating type locus, a/alpha or a/a/alpha/alpha, prevents expression of the overproduction, while homozygosity, a/a and alpha/alpha, and hemizygosity, a/0 and alpha/0, allow full expression of the CYC7 H2 mutation, equivalent to the expression observed in a and alpha haploid strains. There is no decrease in the overproduction of iso-2-cytochrome c in a/alpha diploid strains containing either of the other two similar mutations, CYC7-H1 and CYC7-H3. It appears as if active expression of one or another of the mating-type alleles is required for the overproduction of iso-2-cytochrome c in CYC7-H2 mutants. PMID- 6254833 TI - [Tn9 integration sites and their effect on transposon properties]. AB - The insertion of transposable deoxyribonucleic acid sequence that specifies chloramphenicol acetyltransferase (Tn9) occurs in the preferential sites of the Escherichia coli K-12 chromosome. It is found that some strains of E. coli K-12 have different preferential sites for the Tn9 insertion, located in various regions of the chromosome. The IS1 element inserted into the galT gene of the N116 strain (insertion mutation galT 116:IS1) serves as a strongly preferential site for the Tn9 insertion in this strain. However, being transferred into the chromosome of the KS836 strain this element loses such preference. It was demonstrated that the transposons (Tn9) inserted into different chromosomal sites are distinguished by such properties as stability, different capability to transposition into genomes of bacteriophages and plasmids, and by the choice of the preferential sites of integration in the course of subsequent insertions. PMID- 6254834 TI - [Molecular structure of hybrid phage phi80hy43]. AB - The phage hybrid phi80hy43 derived from a vegetative cross phi80cIhlambda x lambdacIc17 was constructed for discrimination phi80mono- and polylysogens. Molecular structure of this hybrid was established using heteroduplex analysis and restriction endonuclease EcoRI. It is found that the hybrid phi80hy43 represents a phage phi80 containing a foreign piece of DNA between genes cI and 0. The length of this piece of DNA comprises 0.7%, corresponding to the length of cy-cII region of th phage lambda. So it is believed that the hybrid phi80hy43 was formed due to insertion of the lambdacy region with the mutation c17 into phi80hlambda phage genome. PMID- 6254835 TI - [Transposition of the determinant for penicillin resistance from factor RP1 to hemolysis plasmid Hly195]. PMID- 6254836 TI - A transposing forked-duplication with position effect variegation in Drosophila. PMID- 6254837 TI - Histone genes from Xenopus laevis: molecular cloning and initial characterization. AB - Histone DNA sequences, were detected in Eco RI fragments of total Xenopus laevis DNA, by hybridization with 32P-labeled h22-DNA, a histone gene repeat unit of the sea urchin Psammechinus miliaris. The about 6 kb-size class, which was found to hybridize, was subsequently integrated into the E. coli plasmid pCR1. A clone was isolated that contains a 5.8 kb EcoRI fragment hybridizing with h22-DNA. A physical map was constructed using the restriction endonucleases BamHI, PstI, HincII, BglII, XbaI, PvuII, XhoI, AvaI, SmaI, HinfI and HpaII. The fragment was not cleaved by KpnI, AvaI, SalI and HindIII. Using this restriction map we were able to determine the gene order by hybridization with purified gene probes derived from h22-DNA. The gene order was found to be H3, H4, H2A and H2B. The localization of the H1 gene was not possible, probably due to its greater evolutionary divergence. Part of the sequence of the H3-gene is presented providing unambiguous evidence on the identity, map position and polarity of this gene. PMID- 6254838 TI - Cloning of the replication gene O of E. coli bacteriophage lambda and its expression under the control of the lac promoter. AB - The expression of the replication gene O of bacteriophage lambda was put under the control of the lac promoter-operator region integrated into the pBR322 cloning vehicle. The new plasmid pKK104 was introduced into minicells and the O gene induced by isopropyl-beta-thiogalactoside (IPTG). The O protein could be identified as a major component in extracts from these cells, in association with the cell membrane fractions. The molecular weight of the O protein in SDS gels is about 33 000, and it is metabolically unstable but apparently stable upon isolation as a membrane-associated fraction. PMID- 6254839 TI - Construction and characterization of a bacterial clone containing the hemagglutinin gene of the WSN strain (HON1) of influenza virus. AB - A synthetic dodecadeoxynucleotide primer has been used to prepare a double stranded DNA form of the hemagglutinin (HA) gene of a human influenza virus (WSN strain, HON1). This DNA has been inserted in plasmid pBR322 and cloned in bacterial cells. The insert contains nearly the complete hemagglutinin gene. A restriction map of this insert has been determined and structurally important areas of the HA gene have been sequenced. Amino acid sequences of several regions of the HA protein were deduced from the DNA sequences and compared to the known amino acid sequences of other influenza A viruses. WSN HA shows extensive homology to all influenza A viruses in a few regions, namely the first 17 amino acids of the N-terminus of HA1 (N-terminal polypeptide of HA) and the first 24 amino acids of the N-terminus of HA2 (C-terminal polypeptide of HA). The sequence diverges extensively from other influenza A viruses in most other areas. The sequence of WSN virus HA is similar to that of other HON1 viruses with the exception of the C-terminus of the HA1 peptide. The change in this area may contribute to some of the unique properties of WSN virus among the HON1 viruses. In addition, WSN HA contains a 17-amino-acid precursor before the N-terminus of HA1 and a single amino acid, arginine, connecting HA1 and HA2. PMID- 6254840 TI - Cloning the modification methylase gene of Bacillus sphaericus R in Escherichia coli. AB - The gene coding for the sequence-specific modification methylase methM . BspI of Bacillus sphaericus R has been cloned in Escherichia coli by means of plasmid pBR322. The selection was based on the expression of the cloned gene which rendered the recombinant plasmid resistant to BspI restriction endonuclease cleavage. The gene is carried by a 9 kb BamHI fragment and by a smaller 2.5 kb EcoRI fragment derived from the BamHI fragment. The Bsp-specific methylase level was found to be higher in the recombinant clones than in the parental strain. The methylase gene is probably located on the Bacillus sphaericus chromosome, and not on a plasmid known to be carried by this strain. The recombinant clones do not exhibit an BspI restriction endonuclease activity. PMID- 6254841 TI - Expression of thymidylate synthetase activity in Bacillus subtilis upon integration of a cloned gene from Escherichia coli. AB - The gene from Escherichia coli encoding thymidylate synthetase was cloned in the plasmid pBR322. The resulting chimeric plasmid, pER2, was effective in transforming both E. coli and Bacillus subtilis to thymine prototrophy. Uncloned linear E. coli chromosomal DNA was unable to transform thymine-requiring strains of B. subtilis to thymine independence. Linearization of the chimeric plasmid, pER2, with restriction enzymes markedly diminished its ability to transform B. subtilis auxotrophs. The Thy+ transformants derived from the transformation of B. subtilis with pER2 DNA did not contain detectable extrachromosomal DNA as demonstrated by Southern hybridization patterns and centrifugation in CsCl gradients of DNA isolated from B. subtilis colonies transformed with the chimeric plasmid. We conclude that the DNA from the chimeric plasmid was integrated into the chromosome of B. subtilis, demonstrating that extensive homology is not required for the integration of foreign DNA. This is the first reported case of a gene from a Gram-negative bacterium functioning in a Gram-positive organism. PMID- 6254843 TI - A bacteriophage lambda vector for cloning large DNA fragments made with several restriction enzymes. AB - Lambda derivatives are described that can be used for cloning DNA fragments of about 20 kilobase pairs (kb) generated by restriction enzymes EcoRi, HindIII, BamHI, MboI and BglII. Recombinants can be selected by their Spi- phenotype and their propagation is facilitated by the presence of a chi site. PMID- 6254842 TI - Isolation of recombinant plasmids and phage carrying the lexA gene of Escherichia coli K-12. AB - The lexA gene of Escherichia coli K-12 was cloned from the plasmid pLC44-14 into pBR322. Plasmids carrying lexA+ were selected by their ability to complement a recessive tsl mutation, which is believed to be a mutation in lexA. The smallest lexA+ recombinant plasmid, pJL21, contained an EcoRI-PstI fragment 2.9 kilobases (kb) in length; two larger plasmids also contained this fragment, and genetic material to one or both sides of the EcoRI-PstI fragment. Plasmids homologous to pJL21, but carrying a dominant mutation, lexA3, or one of three recessive amber mutations in lexA, termed spr, were also isolated. To clone the EcoRI-PstI fragment onto a lambda vector, the PstI end was first converted to an EcoRI end by attachment of a 100-base pair PstI-EcoRI fragment isolated from the plasmid ColE1; the resultant EcoRI fragment was then cloned into the lambda vector lambda gt4. A restriction map of pLC44-14 was obtained for nine restriction enzymes. The orientation of this map was determined relative to the E. coli genetic map by complementation of the gene ubiA+ and by comparison with restriction enzyme digests of another plasmid, pLC11-9, which carries dnaB, a gene closely linked to lexA, but does not carry lexA. PMID- 6254844 TI - Bacteriophage lambda cloning vehicles for studies of genetic recombination. AB - A pair of bacteriophage lambda cloning vehicles has been constructed for use in studies of genetic recombination. These phages, lambda rva and lambda rvb, have the following properties: (1) Each vector has a single HindIII site in the immunity region, at which segments of DNA can be inserted. (2) These HindIII sites are flanked by selectable markers with the following phenotypes: Spi+/- (Fec+/-) to the left, and imm lambda or imm434 to the right. (3) There is essentially no sequence homology between the two phages in this region, so recombination of the markers at reasonable frequency depends on the presence of homologous inserts at the HindIII sites. As a consequence, recovered recombinants must have resulted from a crossover event within the insert DNA. Restriction enzyme maps of the vectors have been determined. Variants of the original vectors have been isolated which permit separate examination of the viral (Red) and bacterial (Rec) generalized recombination mechanisms, and which provide a standard interval to which frequencies of recombination in cloned DNAs can be compared. PMID- 6254845 TI - Recombination of a eukaryotic DNA in bacteria. AB - Single, 824 bp repeating units of xenopus laevis oocyte-type 5S DNA were inserted into the recombination vectors, lambda rva and lambda rvb. When the inserts had the same orientation with respect to the lambda chromosomes. Spi- imm434 recombinants were recovered by selection on a P2, lambda double lysogenic host. Because of the structure of the vectors, the crossover point in each recombinant must lie completely within the 5S DNA insert. The physical characteristics of these recombinants were determined by examination of restriction enzyme digests. By use of RecA mutant hosts and the Red- vector, lambda rvc, recombination frequencies were measured separately for the bacterial and phage systems. Some of the recombination events resulted in 5S DNA inserts of altered length due to unequal crossovers within repeated sequences in the 5S DNA spacer. The occurrence of just such events in frog 5S DNA had been predicted, based on the structure of 5S DNA and evolutionary considerations. PMID- 6254846 TI - Direct fractionation of genes by preparative electrophoresis of Bacillus subtilis DNA. AB - Discontinuous electrophoresis through agarose has been shown to be a satisfactory method for preparation of biologically active restriction fragments from milligram quantities of DNA. The DNA is obtained in sufficient quantity for: (1) direct use in genetic transformation, (2) the production of multiple-dimensional restriction analyses, or (3) use as a high-resolution hybridization probe. PMID- 6254847 TI - Complex molecular structure of the gene coding for rat ceruloplasmin. AB - The distribution of ceruloplasmin-coding sequences among the fragments of rat nuclear DNA obtained after the complete digestion with seven restriction endonucleases (EcoRI, BamHI, BspI, HindIII, KpnI, BglII and XhoI) was studied using highly specific cDNA probes. Although only a single copy of this gene per rat haploid genome was detected in DNA-cDNA hybridization in solution, the number of restriction fragments carrying the sequences of ceruloplasmin (CP) gene varied from two to five, depending upon the enzyme used, and their total length was several times higher than the minimal length of CP-coding gene, as deduced from the size of mRNA (2.3 Md for double-stranded DNA). The partial double stranded DNA transcript of ceruloplasmin mRNA coding for about 70% of its length (from 3' end) does not contain recognition sites for some restriction endonucleases generating multiple fragments of CP gene in cellular DNA. These data are consistent with a split pattern of CP gene which seems to consist of several exons and introns. The partial protection from S1 nuclease of discrete fragments of full-length cDNA after annealing with high molecular weight nuclear RNA is consistent with this assumption and seems to be an indication that exons and introns are joined into a functional unit coding for high mol wt. CP pre-mRNA. PMID- 6254848 TI - A cloning vehicle suitable for strand separation. AB - A new plasmid has been constructed which contains a poly(A) : poly(dT) duplex segment of length approx. 100 base pairs (bp) inserted into the PvuII site of pBR322. This plasmid, pKH47, has all the other restriction sites of pBR322 available for insertion of foreign DNA, and has the same drug resistance genes as does the parental plasmid. The complementary strands of the linearized denatured plasmid DNA can be separated rapidly an efficiently by affinity chromatography with oligo(dA)- and oligo(dT)-cellulose columns in series. More than 90% of the input DNA is recovered as separated strands which can be annealed to form full length double-stranded molecules. One of the applications of the plasmid is to prepare separated complementary strands for sequencing by the chain-terminator technique using DNA primers. This application is illustrated by a sequencing example for a Drosophila DNA insert carrying a tRNA gene. PMID- 6254849 TI - Nucleotide sequence of the filamentous bacteriophage M13 DNA genome: comparison with phage fd. AB - The 6407 nucleotide-long sequence of bacteriophage M13 DNA has been determined using both the chemical degradation and chain-termination methods of DNA sequencing. This sequence has been compared with that of the closely related bacteriophage fd (Beck et al., 1978). M13 DNA appears to be only a single nucleotide shorter than fd DNA. There is an average of 3.0% of nucleotide sequence differences between the two genomes, but the distribution of these changes is not random; the sequence of some genes is more conserved than of others. In contrast, the nucleotide sequences and positions of the regulatory elements involved in transcription, translation and replication appear to be identical in both filamentous phage DNA genomes. PMID- 6254850 TI - The cII-independent expression of the phage lambda int gene in RNase III defective E. coli. AB - This study compares the rates of lambda protein synthesis after infection of rnc- cells, which are defective in ribonuclease III (RNase III), with the analogous rates in an isogenic rnc+ host. Temporal differences in gene expression are reflected in a delay in turn-off of lambda early proteins as well as in the delayed appearance of late phage functions in rnc- host cells. Moreover, in the two hosts there is a striking difference in the regulation of gene int expression, which in wild-type cells requires the product of the lambda cII (and cIII )genes, whereas Int synthesis occurs in the absence of cII in RNase III defective cells. These results suggest that RNase III may be a negative regulator of Int synthesis. The expression of int is also shown to be cII- and cIII independent in rnc+ cells infected with b2-deleted phages, thus confirming previous studies on the negative regulation of int by the b2-region. Possible mechanisms of these two inhibitory effects on int expression are considered and the significance of int regulation in the control of site-specific recombination is discussed. PMID- 6254851 TI - A physical map of the genome of the Bacillus subtilis temperate phage rho 11. AB - A cleavage map of Bacillus subtilis temperate phage rho 11 was constructed with restriction endonucleases SalI, BamHI and BglII, which cut the genome into 6, 7 and 21 fragments, respectively. The molecular weight of the rho 11 genome was calculated to be 78 x 10(6). Among other endonucleases tested, PvuII, EcoRI and XbaI cleaved the genome into more than 25 fragments, while HaeIII, StuI, BalI and BamNx did not cut the genome at all. The rho 11-coded thymidylate synthetase gene, thyP11, was found to be located in the SalI-D fragment, which was in the central region of the genome. PMID- 6254852 TI - A cautionary note on the use of certain restriction endonucleases with methylated substrates. AB - Methylation of adenine and cytosine residues in DNA isolated from common strains of Escherichia coli K-12 can render that DNA resistant to cleavage by certain restriction endonucleases at those sites at which the recognition sequence for such an endonuclease overlaps (but does not include) a sequence recognized by methylases specified by the dam or dcm gene. PMID- 6254853 TI - Physical localisation and cloning of the structural gene for E. coli initiation factor IF3 from a group of genes concerned with translation. AB - The structural genes for translational initiation factor IF3, threonyl-tRNA synthetase (TRS), the two subunits of phenylalanyl-tRNA synthetase (PRS), and a 12 000 mol. wt. protein of unidentified function are carried by the lambda p2 transducing phage. The localization of these genes on a restriction map of the Escherichia coli DNA insert was achieved by deletion mapping. In addition a set of plasmids carrying fragments of the original phage was constructed and helped to confirm these assignments. One plasmid, containing a 3.3 kb PstI fragment inserted into pBR322, does not code for any of the synthetase genes but causes strains carrying it to overproduce IF3. PMID- 6254854 TI - Nucleotide sequence of a cloned fragment of rat mitochondrial DNA containing the replication origin. AB - The nucleotide sequence was determined for the 717 bp HapII subfragment (HapEcoA5) of the EcoRI-A fragment of rat mitochondrial DNA, which contains the heavy-strand replication origin. Analysis of the heavy-strand initiation segments released from the D-loop molecules has revealed that some 5'-ends of these initiation segments are linked to ribonucleotide(s) and are heterogeneous. Sequence analysis of the 5'-end portion of the initiation segment indicated that one of the start points of the deoxyribonucleotide polymerization corresponds to the 425th bp on the HapEcoA5. Two-fold rotational symmetry and palindrome structures, and a G-cluster sequence around the start point have been discussed in connection with unidirectional replication. PMID- 6254855 TI - Construction of an SV40-derived cloning vector. AB - A new reiterated variant of simian virus 40 (SV40; dl1142) has been constructed. It should be useful for the purpose of cloning foreign pieces of DNA in SV40 virions. Up to 80% of the SV40 genome has been made available for substitution with foreign DNA and the vector contains a number of unique (single-cut) restriction sites which will facilitate cloning. The 5' and 3' regions of both the SV40 early and late messenger RNAs are included in the vector. Prokaryotic DNA has been successfully cloned in the early region of the vector. The transcriptional properties of the recombinant have been studied, and it was found that both the vector and insert DNA are transcribed, mainly as non-adenylated RNA. PMID- 6254856 TI - Divergence of primate ribosomal RNA genes as assayed by restriction enzyme analysis. AB - Primate ribosomal RNA (rRNA) genes have been compared by restriction endonuclease mapping. In all species examined, the restriction map of the reiterated ribosomal DNA is simple (within the limits of detection by hybridization with rRNA) and is consistent with a high degree of homogeneity among the repeats. Within a species, all members have similar rDNA restriction patterns. However, different species of primates have distinctly different rDNA restriction maps; even chimpanzee and man can be discerned by their rDNA restriction patterns. Possible mechanisms for maintenance of homogeneity of the rDNA repeats within a species, while allowing divergence among closely related species, are discussed. PMID- 6254857 TI - [Determination of maximum permissible concentration of polycarbacide in the water reservoirs]. PMID- 6254858 TI - [Methodological problems of standardization of dust of complex chemical composition]. PMID- 6254859 TI - Effects of delta-9-tetrahydrocannabinol on cultured HeLa cell growth and development. AB - Monolayer cultures of HeLa cells were used to monitor the effects of non-lethal concentrations of delta-9-tetrahydrocannabinol (delta-9-THC) on the pool sizes of the acid-soluble and acid-insoluble DNA moieties and cytoplasmic RNA pool sizes. The DNA fractions were separated using acid precipitation and low speed centrifugation, while the RNA was examined through the use of sucrose gradients and high speed ultracentrifugation. The ratio of acid-insoluble to acid-soluble DNA per cell in untreated HeLa cells is 16:1, which did not change appreciably following delta-9-THC treatment. However, cell division was retarded as much as 25% in the 24 hours treatment period indicating that nucleic acid synthesis, while not inhibited, is depressed by delta-9-THC. This is not related to cell death as indicated by cell viability (> 95%). At both 1.0 x 10(-5)M and 3.2 x 10( 7)M, delta-9-THC caused a marked change in the free ribosomal RNA (an increase with 3.2 x 10(-7)M and a decrease with the 10(-5)M), total ribosomal RNA (a decrease with both observed delta-9-THC concentrations) and non-sedimental RNA (an increase with both observed delta-9-THC concentrations). PMID- 6254860 TI - [Fibrous histiocytoma of the lung]. PMID- 6254861 TI - [Peripheral neuropathy in dysglobulinemic states]. PMID- 6254862 TI - [Evaluation of hormonal treatment of threatened abortion]. PMID- 6254863 TI - Wilms' tumour - diagnostic and prognostic problems. PMID- 6254864 TI - Quantitative analysis of the incidence of lamellar inclusion bodies in granular pneumocytes. PMID- 6254865 TI - Episodic corticosterone secretion in the female rat. AB - Studies conducted in several laboratories have shown primate glucocorticoid secretion to occur episodically. In light of the methodological, as well as physiological importance of this finding, the present study was undertaken to determine whether the rat corticosteroid secretion also occurs episodically. Female rats were outfitted with chronic intravenous cannulas, and 1 week later 200 units of heparin were injected through the implanted cannula and blood samples (0.3-0.4 ml) were collected from each rat every 10 min for 3 h during the morning (06.00-10.00 h) or during the afternoon (16.00-19.00 h) (lights on from 05.00 to 19.00 h). Plasma corticosterone levels in cannulated rats showed fluctuations indicative of episodic secretion. The pattern of plasma corticosterone levels was characterized by periodic rapid increases in hormone concentration during both the morning and afternoon sampling periods; the occurrence of these hormonal fluctuations did not have a characteristic frequency. When the data were grouped to obtain single morning and afternoon values, the AM-PM difference was significant (p < 0.005). Collectively, these data suggest that in the rat, adrenal corticosteroids are secreted episodically. PMID- 6254866 TI - Demonstration of luteinizing hormone/human chorionic gonadotrophin receptor binding inhibitor in aqueous extracts of frozen human corpus luteum. AB - Aqueous extracts of frozen human corpora lutea were tested for the presence of an inhibitor of luteinizing hormone-receptor site binding (LHRBI) and for the subsequent effect on the stimulatory response of luteinizing hormone (LH) on progesterone synthesis by sheep ovarian cells. In the presence of human corpus luteum extract of normal menstrual cycle (30,000-g supernatant), the binding of 125I human chorionic gonadotrophin (hCG) to granulosa and luteal cells of sheep ovaries was markedly reduced, but the ability of rat testicular LH receptors to bind labelled hCG was less affected. However, extracts of corpora lutea of the first trimester of pregnancy appeared to be less inhibitory on the binding of LH/hCG to ovarian cells and had no effect on the binding of rat testicular cells compared to those of normal menstrual cycle. Addition of both extracts separately inhibited the LH-stimulated in vitro progesterone synthesis by granulosa cell cultures and by incubated sheep corpus luteum slices. These findings provide evidence for the presence of LHRBI in human corpus luteum. PMID- 6254867 TI - Thiamphenicol as an inhibitor of early red cell differentiation. AB - The effects of an in vivo treatment of mice with thiamphenicol on stem cells are shown. Thiamphenicol causes a drastic depletion of erythroid precursors in the marrow. Mitochondrial protein synthesis is inhibited resulting in a severely reduced cell proliferation. The number of pluripotent stem cells in the marrow did not decrease. In the spleens of thiamphenicol-treated mice a strong reduction of stem cells was found. The sedimentation behaviour of stem cells from anemic and thiamphenicol-treated mice was similar. The pluripotent stem cells from thiamphenicol-treated mice were in a low cycling state, despite a very high erythropoietin level. Under these circumstances a partial commitment of the pluripotent stem cells into the erythroid direction was observed. PMID- 6254868 TI - Endocrine differentiation in mucoid carcinoma of the breast. AB - Mucoid carcinoma of the breast is not a single homogeneous entity. It comprises two main variants separable on structural and cytological grounds and a smaller transitional type. The salient pathological differences are detailed. One variant is usually arygrophilic and contains dense core granules of the type seen in endocrine tumours. Both endocrine and amphicrine cells have been identified in this sub-type. The relationship of this endocrine variant of mucoid carcinoma to other argryophil carcinomas (so-called 'carcinoids') of the breast is discussed. PMID- 6254869 TI - Mitogenicity of Entamoeba histolytica extracts for murine lymphocytes. AB - Aqueous extracts or aqueous extracts of delipidated Entamoeba histolytica (E.h.e.) contain a mitogenic principle for murine lymphocytes. As detected by [3H]-thymidine incorporation and blast transformation, E.h.e. acted predominantly on T cells of splenic origin, but not on thymocytes or bone marrow cells. Furthermore, E.h.e. induced proliferation of a subset of non-T-cells which is present in the spleen of athymic nude mice, adhered to nylon wool, but could not be activated to produce antibody. It seems possible that polyclonal activation of lymphocytes by E. histolytica might play a role in the disturbance of the immune system as manifested in the impaired cell mediated immune response of E. histolytica infected hosts. PMID- 6254870 TI - Cyclic adenosine 3, 5'-monophosphate phosphodiesterase activity in normal & neoplastic murine mammary gland. PMID- 6254871 TI - Effects of degranulatory techniques on certain phosphatases of rat brain-cortex microsomes. PMID- 6254872 TI - Regulation of dopamine-beta-hydroxylase in vitro in rat heart & adrenal tissue. PMID- 6254874 TI - Control of cell proliferation in transformed cells. AB - We have presented evidence that T-ag of SV40 reactivates silent rRNA genes. Since rRNA synthesis correlates with growth rates, it is conceivable that T-ag may stimulate cell proliferation by acting on rRNA genes. In SV40-transformed, T positive cells, this would and does result in continuous cell proliferation, beyond the limits of that in normal cells. PMID- 6254873 TI - Resistance to HSV-1 in the mouse is governed by two major, independently segregating, non-H-2 loci. AB - Earlier studies showed that genetic resistance of adult, inbred strains of mice to Herpes Simplex Virus-type 1 (HSV-1) is a dominant genetic trait. The present studies were undertaken to determine the number of genetic loci involved and whether they were found within the major histocompatibility complex, H-2, of the mouse. Challenge with HSV-1 of progeny of mice backcrossed to moderately susceptible BALB/c mice, of progeny of mice backcrossed to very susceptible A/J strain mice, and of progeny of the F-2 cross using (C57BL/6 x A/J)F1 mice indicated that two major loci were responsible for resistance. The backcrosses to BALB/c mice suggested that additional genes on this background enhanced resistance, while further backcrosses with the A/J mice indicated that other genes on the A/J background (or the lack thereof) reduced resistance. Studies with congenic mice showed that genes within the H-2 did not influence resistance or susceptibility. PMID- 6254875 TI - Lymphocyte-derived chemotactic factor synthesis in initial genital herpesvirus infection: correlation with lymphocyte transformation. AB - Lymphocyte transformation and production of lymphocyte-derived chemotactic factor in response to herpes simplex virus antigen were studied in 15 patients with initial genital herpes and 10 controls. The patients underwent frequent genital examinations, viral cultures, and weekly immunological studies for a period of 11 weeks. The production of lymphocyte-derived chemotactic factor was maximal in week 1 of the disease and declined to control levels by week 6. In contrast, lymphocyte transformation was lowest in week 1, reached a maximum by week 4, and declined to control levels by week 11. Production of lymphocyte-derived chemotactic factor in week 1 was significantly lower in nine patients who developed signs or symptoms of systemic herpes infection than in six who had localized disease. In addition, a marked but transient decline in the production of this lymphokine was observed in patients at the time of clinical recurrence. Virus-specific lymphocyte transformation correlated inversely with the duration of genital pain and lesions and did not correlate with the presence of systemic signs or symptoms. These findings indicate that during initial genital herpes infection the dynamics of lymphocyte transformation and those of lymphocyte derived chemotactic factor production are different, and that the generation of this lymphokine is an early component of the cellular immune response in this disease. Furthermore, adequate produce of lymphocyte-derived chemotactic factor may be important in restricting herpes simplex virus to the genital area and preventing disease recurrence. PMID- 6254876 TI - Seroconversion to virus-specific pre-early nuclear antigens in infants with primary cytomegalovirus infection. AB - Antibodies to human cytomegalovirus (CMV)-specific antigens were determined in sera serially collected from 10 infants with primary CMV infection. Antibodies to pre-early nuclear antigens (PENA), which are detectable in human embryonic lung cells within 3 h of CMV infection by anticomplement immunofluorescence staining, developed in all the patients. However, in contrast to the early response of anti early antigens (EA), anti-late antigens (LA), and immunoglobulin M antimembrane antigens (MA), seroconversion or the maximum antibody response to PENA was usually observed 1 or more months later. Immunoglobulin M antibody to MA became undetectable soon after recovery from illness, followed by a decrease in anti-EA, anti-PENA, and then anti-LA titers. Results indicated analogy of the clinical significance of anti-PENA in CMV infection to that of anti-Epstein-Barr nuclear antigen in infectious mononucleosis and support the idea that parallel determinations of anti-PENA and IgM anti-MA antibodies can be useful for identifying the acute or chronic phase of primary CMV infection. PMID- 6254877 TI - Pathogenicity of wild-type and temperature-sensitive mutants of herpes simplex virus type 2 in guinea pigs. AB - The pathogenicity of herpes simplex virus type 2 strain 186, the wild-type (WT) strain, and four temperature-sensitive (ts) mutants was studied after genital inoculation of female guinea pigs. Infection with the WT virus was generally severe, with extensive skin lesions in 89% and mortality in 37% of inoculated animals. Guinea pigs inoculated with ts mutants manifest remarkably mild disease, with lesions occurring in only 16% of the guinea pits and a mortality rate of 7%. WT virus was recovered from nerve and non-nerve tissues of all acutely infected animals and from the majority of latently infected animals (71%). Virus was isolated from nerve or genital tissues from only 13% of ts mutant-inoculated animals during acute infection and from 7% during latent infection. Three of the seven isolates from mutant-infected animals appeared to be WT virus. Identification of WT and ts mutant isolates was done by biological characterization in selective cell cultures at permissive (33 degrees C) and nonpermissive (38 degrees C) temperatures. One month after initial infection with WT virus, guinea pigs were challenged with the same virus and were completely resistant to overt clinical disease. Animals inoculated with ts mutants A1b and C2b had mild manifestations of disease after challenge with WT virus; however, the capacity of WT virus to establish latent infection was conserved. Although complement-required neutralizing antibodies were detectable after challenge in animals previously inoculated with mutant virus A1b, C2b, or D6b, there was no significant protection against subsequent infection with WT virus. No complement required neutralizing antibodies were detected in F3b animals after challenge. The present study of WT and ts mutants of herpes simplex virus type 2 in the guinea pig model provides a means for better understanding the mechanisms of pathogenesis and latency after genital infection. PMID- 6254878 TI - Mechanisms of herpes simplex virus infectivity enhanced by ultracentrifugal inoculation. AB - Ultracentrifugation of very dilute suspensions of herpes simplex virus directly onto monolayer cells grown in centrifuge tubes was studied. Enhanced infectivity by ultracentrifugation was similar at 4 degrees C and at 35 to 37 degrees C. The high infectivity levels of cultures centrifuged at 4 degrees C were further examined by infectious center assays. At 4 degrees C, the numbers of infectious centers in control (noncentrifuged) cultures were almost 100-fold fewer than in control cultures at 37 degrees C. However, the numbers of infectious centers in cultures ultracentrifuged at 4 degrees C were similar to those ultracentrifuged at 37 degrees C. The great difference in the numbers of infectious centers between 4 and 37 degrees C control cultures, in contrast to the similarity between 4 and 37 degrees C ultracentrifuged cultures, indicated that ultracentrifugation at 4 degrees C enhanced infectivity possibly by facilitation of herpes simplex virus penetration into monolayer cells. PMID- 6254879 TI - Partial characterization of a bactericidal system in staphylococcal abscesses. AB - Since leukocytes comprise a major portion of staphylococcal abscesses, the properties of the bactericidal material in abscess homogenates were compared with those of bactericidal systems associated with leukocyte lysosomes. The bactericidal material in abscess homogenates was distinguished from the myeloperoxidase system by its resistance to heat (100 degrees C, 30 min), lack of solubility in dilute acid (0.005 N HCl), resistance to strong acid (pH 1), and insensitivity to catalase. It was differentiated from the cationic proteins by its lack of solubility in dilute acid, insensitivity to iron (0.1 mM) or trypsin (5 mg/ml), and greater activity in solutions of increased ionic strength. These characteristics, together with its sensitivity to Ca2+ or albumin, suggested that the material might be lipid. Subsequent studies revealed that all the bactericidal activity resided in the lipid fraction recovered after extraction of abscess homogenates by the Dole procedure. PMID- 6254880 TI - Separation of Sendai virus glycoproteins by using glutaraldehyde-treated erythrocytes and preparation of monospecific antisera against the glycoproteins. AB - Sendai virus hemagglutinin-neuraminidase (HN) and fusion (F) glycoproteins, F and HN, were separated from Triton X-100- or Nonidet P-40-solubilized envelopes as unadsorbed and eluted fractions, respectively, by using glutaralde-hyde-treated chicken erythrocytes. These separated glycoproteins were biologically active. Monospecific antisera (in terms of monoreactivity to virus glycoproteins in gel diffusion precipitation patterns) were prepared by using these fractions as immunogens. Anti-HN rabbit serum inhibited all of the viral activities tested (infectivity, neuraminidase, hemagglutinating, and viral hemolysis), whereas anti F serum definitely inhibited viral hemolysis only, although the two antisera enhanced neutralization in the presence of complement. The advantages and disadvantages of this separation method were discussed. PMID- 6254881 TI - Secretory immunological response in infants and children to parainfluenza virus types 1 and 2. AB - The secretory immunological responses to natural infection with parainfluenza viruses ae not well defined. Nasopharyngeal secretion specimens from 20 infants and children naturally infected with parainfluenza virus type 1 or type 2 were examined for class-specific antibody and virus-neutralizing activity. There was a marked discordance in individual secretions between immunoglobulin A (IgA) antibody (as measured by indirect immunofluorescence) and neutralizing activity (as determined by either hemadsorption plaque or 50% tissue culture infective dose reduction) to the infecting parainfluenza virus type. Many secretions contained neutralizing activity in the absence of detectable IgA antibody; conversely, secretions with measureable IgA antibody frequently lacked neutralizing activity. Moreover, there was no relationship between neutralizing activity and the course of illness. All 11 patients with serial secretion specimens showed a fourfold or greater titer rise in IgA antibody to the homologous parainfluenza virus type. Antibody usually appeared 7 to 10 days after the onset of symptoms and peaked at about 2 weeks. This response did not appear to be related to age or to severity of illness. in general, the secretory responses resembled those seen in infants infected with respiratory syncytial virus. PMID- 6254882 TI - Humoral and cell-mediated immune mechanisms in the production of pathology in avirulent Semliki Forest virus encephalitis. AB - Seven days after peripheral inoculation with an avirulent strain of Semliki Forest virus, the brains of CBA and nude mice exhibited a mononuclear inflammation and spongiform degeneration. Mice that had received cyclophosphamide (150 mg/kg) 24 h after infection showed no pathology until day 11. However, immunofluorescence studies of the brains of immunosuppressed, infected mice demonstrated viral antigen within the soma and processes of neurons at earlier periods. The brain lesions could be reconstituted on day 7 in immunosuppressed, infected recipients with 6-day immune spleen cells. Immune spleen cells depleted of T lymphocytes, the non-immunoglobulin-bearing population deficient in B lymphocytes, or immune sera plus nonimmune bone marrow cells could also reconstitute the lesions. However, inflammation and spongiform changes were reduced when donor immune cells were depleted of either T or B lymphocytes. When both T and B lymphocytes were removed from the donor immune population, recipient brains did not show pathology. The results demonstrate that either antibody or immune T cells can trigger pathology, but there is also participation of nonimmune bone marrow-derived mononuclear cells, probably of the monocyte macrophage lineage. PMID- 6254883 TI - Serological investigation of BK papovavirus infection in pregnant women and their offspring. AB - Paired sera from 150 pregnant women and 387 umbilical cord sera were tested for BK virus (BKV) antibodies. The hemagglutination inhibition, neutralization, and indirect immunofluorescence tests were employed for the detection of antibodies. Treatment of serum with anti-gamma Fc and tests of immunoglobulin M (IgM) fractions for antibodies were utilized as required to detect and validate the presence of virus-specific IgM. The BKV antibody prevalence in the sera collected at the time of the first prenatal visit was 75% by hemagglutination inhibition and 91% by neutralization tests. A total of 95% of the women had antibodies by at least one of the three serological tests. Five of 100 women with normal pregnancies exhibited BKV activity during pregnancy as evidenced by a greater than fourfold rise in BKV hemagglutination inhibition antibody titers and acquisition of BKV-specific IgM. The antibody rise occurred in the younger women and appeared to be a result of reactivation of the virus rather than of primary infection. Two instances of possible recent BKV infections were identified. BKV specific IgM was not detected in any of the 387 umbilical cord sera which included three specimens from infants born to mothers with definite or probable BKV activity during pregnancy and 50 specimens with IgM levels of > 20 mg/100 ml. The results indicate that few women in the child-bearing age are nonimmune to BKV and that, although reactivation of infection occurs in pregnancy, congenital transmission of the virus either does not occur or is rare. PMID- 6254884 TI - Identification of a chromosomal determinant of alpha-toxin production in Staphylococcus aureus. AB - Production of alpha-toxin (the Hla+ phenotype, controlled by the Hla gene and scored as alpha-hemolytic activity) is a property of some isolates of Staphylococcus aureus NCTC 8325 and not of others. Genetic transformation between strains differing in the Hla phenotype revealed that the hla+ gene resides in the following sequence: purB110-bla+-hla+-ilv-129-pig-131; previously, the enterotoxin A (entA) gene of strain S-6 was shown to map very close to hla+. The hla+ mutations occurring naturally in strain Ps6 and after various mutagenic treatments in strains 8325 and 233 also mapped between bla+ and ilv-129. Among the isolates of strain 8325, the Hla+ phenotype was always associated with fibrinolytic activity, whereas Hla- isolates were non-fibrinolytic. This relationship was also observed among transformants selected for their Hla+ or Hla phenotypes. The failure of Hla- strains and mutants to revert to hla+ at detectable frequencies, the instability of the Hla+ phenotype, and the previously observed pattern of recombination of the hla+ and entA+ determinants lend support to the view that hla+ may reside on a transposon; according to this view, Hla- mutants have lost the hla+-bearing transposon. It remains unclear whether hla+ is the structural gene for alpha-toxin. PMID- 6254885 TI - Partial purification and properties of a mannofructokinase from Streptococcus mutans SL-1. AB - Fructokinase activity was demonstrated in seven strains of oral streptococci. The enzyme purified from Streptococcus mutans SL-1 was capable of phosphorylating both D-fructose and D-mmannose to their respective 6-phosphates. Phosphorylation of both fructose and mannose was dependent on adenosine 5'-triphosphate and a divalent metal ion. The molecular weight of the purified enzyme was estimated to be 49,000. The apparent Km of the enzyme for fructose was 0.63 mM. This enzyme also utilized mannose as a substrate, with an apparent Km for mannose of 0.37 mM. Since the activities of the enzyme toward mannose and fructose were not separated upon purification of the enzyme and since mannose was a competitive inhibitor of fructose phosphorylation, the purified kinase is a single enzyme, mannofructokinase, with dual specificity for both mannose and fructose. A role for this enzyme in carbohydrate metabolism in S. mutans is postulated. PMID- 6254886 TI - Immunity to herpes simplex virus type 2: cell-mediated immunity in latently infected guinea pigs. AB - Cell-mediated (CMI) and humoral immunity to herpes simplex virus type 2 (HSV-2) were evaluated in infected strain 13/N guinea pigs with (45%) and without a history of recurrent herpetic disease. Virus was isolated by cocultivation from active herpetic lesions (9 of 10) as well as from the footpads (17 of 38), sacral ganglia (7 of 21), and sciatic nerves (1 of 21) of asymptomatic animals. Viral isolates grew in cells of human origin and were neutralized by hyperimmune anti HSV-2 sera. Humoral immunity measured by the presence of virus-neutralizing antibody was similar in both experimental groups. The involvement of CMI in recurrent disease was assessed by comparing lymphocyte transformation (LT) and leukocyte migration inhibition factor (LIF) responses in animals with a history of recurrent disease studied while asymptomatic (quiescent) and in animals without clinical evidence of recurrent disease (seropositive controls). Spleen cells from quiescent animals evidenced significant impairment of both LIF and LT responses as reflected in the requirement of higher antigen concentrations (up to 58-fold) and longer in vitro culture periods (up to 2.5 days) to mount responses comparable in magnitude to those observed in the seropositive control groups. Peripheral blood lymphocyte cultures obtained from quiescent animals showed similar impairment of LIF responses but displayed intact LT response. The data suggest that recurrent disease is associated with an impairment in the generation of anamnestic effector functions as reflected by altered kinetics and dose response patterns in in vitro secondary responses. PMID- 6254888 TI - Aerosol stability and respiratory infectivity of japanese B encephalitis virus. AB - Experiments were conducted to examine the aerosol stability and respiratory infectivity of Japanese B encephalitis virus. At 75 degrees F (about 24 degrees C), survival of the virus as aerosol was inversely related to relative humidity. After correction for physical decay, the mean virus half-lives of the virus were 28, 38, and 62 min at relative humiditis of 80, 55, and 30%, respectively. Virus recoveries as aerosol at 4 min aftr dissemination generally exceeded the theoretical limit of 100%, based on the amount disseminated, to suggest that the process of dissemination operated to deagglomerate or release bound virus from the tissue cells in suspension. Swiss-ICR mice and golden Syrian hamsters were highly susceptible to lethal infections after respiratory challenge. Hartley strain guinea pigs and Fisher-Dunning rats, although infected, based on seroconversion observations, survived the infections. Deaths occurred in squirrel monkeys only after exposure to a high aerosol dose of virus (10(6.0) plaque forming units). Studies of the virus concentration dynamics and histopathological findings in mouse tissues after aerosol challenge supported a hypothesis for direct transport of virus across the foramina of the cribriform plate to the tissues of the central nervous system to produce primary encephalitis. PMID- 6254887 TI - Comparison of human rotaviruses isolated in Mexico City and in Santiago, Chile, by electrophoretic migration of their double-stranded ribonucleic acid genome segments. AB - During the period October to December 1979, rotaviruses were obtained from infants and young children hospitalized with acute gastroenteritis in Mexico City and were compared by analysis of the migration of their double-stranded ribonucleic acid (RNA) genome segments in gel electrophoresis. Comparison of the results of this analysis and of those of similar studies carried out in 1977 and 1978 showed that the two rotavirus electropherotypes designated 2s and 21 have been continuously present and that the proportion in which these two types have been found in hospitalized patients has varied greatly year to year. The RNAs from rotaviruses 2s and 21 differed in the electrophoretic migraton of at least eight genome segments. However, RNAs from virus assigned to the same electrophoreotypes were not necessarily identical: on the basis of small but significant differences in the migration of segment 7, 8, or 9, isolates of types 2s and 21 could be assigned to two and three different subtypes, respectively. Human rotaviruses obtained in a distant geographical region, Santiago, Chile, in July 1979 had RNA electrophoretic patterns similar to that of electropherotype 21 but different from it in the migration of one or two of the larger RNA segments. PMID- 6254889 TI - Exfoliative toxin plasmids of bacteriophage group 2 Staphylococcus aureus: sequence homology. AB - The plasmid contents of seven exfoliative toxin-producing strains of phage group 2 Staphylococcus aureus were analyzed by agarose gel electrophoresis and deoxyribonucleic acid-deoxyribonucleic acid hybridization. All strains were found to contain a large plasmid with a molecular weight of 27 X 10(6) except for strain RW1005. A comparison of the restriction endonuclease cleavage products by agarose gel electrophoresis showed that the number and size distribution of the fragments of all these Tox plasmids were similar, except for pRW002, which appeared to contain two deletions. Deoxyribonucleic acid-deoxyribonucleic acid hybridization studies confirmed that these plasmids were related to a plasmid which carried the genes for exfoliative toxin B and bacteriocin R1 biosynthesis and that they shared some sequence homology with the penicillinase plasmid pI258 isolated from a phage group 3 S. aureus. PMID- 6254890 TI - Linkage of heat-stable enterotoxin activity and ampicillin resistance in a plasmid isolated from an Escherichia coli strain of human origin. AB - In an Escherichia coli strain of human origin, ampicillin resistance and heat stable enterotoxin activity were shown by EcoRI restriction endonuclease and genetic analysis to be in an 80-megadalton plasmid. PMID- 6254891 TI - Evidence for androgen-dependent phosphodiesterase activity in rat seminal vesicle and epididymis. AB - This paper deals with findings implying the existence of an androgen-dependent phosphodiesterase (PDE) activity in accessory sexual glands (seminal vesicle and epididymis) of the rat. It is suggested that the PDE activity is not a prerequisite for, but merely a modulator of the overall androgenic response. PMID- 6254892 TI - Absence of an association between past infection with hepatitis A virus and primary hepatocellular carcinoma. AB - Serum samples from 77 caucasians of Greek origin with primary hepatocellular carcinoma (PHC) and 77 age- and sex-matched controls were tested for antibody to the hepatitis A virus (anti-HAV). Anti-HAV was detected in 63 patients with PHC (82%) and in 70 controls (91%). These data suggest that past infection with hepatitis A virus is not related to the development of PHC, in marked contrast to the strong association between PHC and HBV. PMID- 6254893 TI - beta-Endorphin: hyperthermia in mice by intravenous injection. AB - Effects of intravenous beta-endorphin on body temperature and body weight loss were studied in naive and morphine-dependent mice. beta-Endorphin at doses 2.6 25.5 mg/kg injected intravenously caused hyperthermia in naive mice as well as in morphine-dependent mice. In addition, beta-endorphin and morphine reduced body weight loss during the morphine withdrawal. PMID- 6254894 TI - Immunochemical studies of adrenocorticotropin using tritium labeled hormone. AB - A radioimmunoassay using specifically tritiated corticotropin (3H-ACTH) of high specific radioactivity (46 Ci/mmol) and full biological activity has been developed. The assay is sensitive to ACTH in the range 200 pg-10 ng. 50% displacement of 3H-ACTH is produced by less than a twofold excess of unlabeled hormone. Immunochemical studies with various ACTH analogs showed that the antiserum recognized the intact molecule better than any of other fragments. PMID- 6254895 TI - beta-Endorphin: radioreceptor binding assay. Relative potency of synthetic analogs with various chain lengths. AB - An assay system is described to measure the specific binding of beta-endorphin to opiate sites (receptors) in rat brain membrane preparations using the tritiated hormone as the primary ligand. By this assay procedure, the radioreceptor activity of beta-endorphin and synthetic analogs with various chain lengths has been determined. The results suggest that both NH2- and COOH-terminal sequences of the molecule are involved in the interaction of beta-endorphin with opiate receptors. PMID- 6254896 TI - beta-endorphin: synthesis of analogs with extension at the carboxyl terminus with high radioreceptor binding activity. AB - Four analogs of human beta-endorphin (beta h-EP) have been synthesized: [Gly31] Beta h-EP-Gly-NH2, [CH3(CH2)4NH231]-beta h-EP, [Gly31]-beta h-EP-Gly-Gly-NH2, and [Gln8, Gly31]-betah-EP-Gly-Gly-NH2. All are more active than beta h-EP in an opiate receptor binding assay. Stepwise extension at the COOH-terminus shows a progressive increase in binding activity. The last analog, which combines extension at the COOH-terminus with elimination of the remaining anionic charge in beta h-EP, is nine times more active than the parent molecule. PMID- 6254897 TI - Synthesis and radioreceptor binding activity of turkey beta-endorphin and deacetylated salmon endorphin. AB - Des-acetylated salmon endorphin and turkey beta-endorphin have been synthesized by the solid-phase method. Relative opiate activities in a radioreceptor binding assay are: human beta-endorphin, 100; des-acetylated salmon endorphin, 169; turkey beta-endorphin, 94. Thus, non-mammalian endorphins can show high activity in a mammalian assay system. PMID- 6254898 TI - Free radicals in dicarboxylic acids: an e.s.r. study of radical conversions in gamma-irradiated single crystals of glutaric acid and glutaric-2,2,4,4-d4 acid. AB - The gamma-radiation-induced free radicals in single crystals of glutaric acid and glutaric-2,2,4,4-d4 acid were studied in the temperature range 77-300 K by e.s.r. techniques. At 77 K the decarboxylation radical and the anion are stabilized. At higher temperatures the decarboxylation radical is found to be converted into a hydrogen abstraction radical with an activation energy of 6.3 +/- 0.5 kcal/mole for the non-deuterated crystal. This radical is stable at room temperature. The anion seems be be converted to an unidentified intermediate radical which in turn is converted to the gamma-acyl radical. An analysis of the g-value anisotropy and of the 13C hyperfine splitting variation for this radical in the deuterated crystal is consistent with the assigned radical structure. By heat treatment the alpha-acyl radical is converted to another form of the hydrogen abstraction radical with an activation energy of 9.6 +/- 0.6 kcal/mole in the deuterated crystal. U.V.-light (gamma = 254 nm) transforms one of the room temperature radicals into the other. PMID- 6254899 TI - E.s.r. of spin-trapped radicals in aqueous solutions of deuterated amino acids and alcohols. AB - Selectively deuterated compounds can be utilized in spin-trapping to obtain conclusive evidence for the structures of the trapped radicals. Radicals formed from DL-alanine-2-d1, DL-alanine-3, 3, 3-d3, DL-alanine-d4, glycine-d5, isopropyl 2-d1 alcohol, isopropyl-d7 alcohol and t-butyl-d9 alcohol were studied. The hydrogen abstraction, deamination and decarboxylation radicals generated from deuterated alanines were investigated by spin-trapping using t-nitrosobutane. Since nitroxides of the type XYZC-CH2-N(O)-tBu which contain an asymmetric centre next to the CH2 group exhibit unequal beta-proton splittings and temperature dependent line width alternations, the effects of temperature on the e.s.r. spectra were studied. By these methods the structures of the trapped radicals were verified and the hyperfine coupling constants could be assigned without ambiguity. In gamma-irradiated polycrystalline amino acids, the observed deuterium exchange can be conveniently surveyed by dissolution in aqueous solutions containing t-nitrosobutane. PMID- 6254900 TI - The effects of metabolism improving agents: an electrophysiological study. AB - The effects of ATP, cytochrome C, meclofenoxate and CDP-choline on the central nervous system were studied electrophysiologically in rabbits. The threshold of arousal reaction and evoked muscular discharges following stimulation of the brainstem reticular formation, evoked muscular discharges in the fore- and hindlimbs on stimulation of the cerebral cortex and the hippocampus, afferent average evoked potential due to stimulation of the sciatic nerve and unit discharges of nerve cells in the brainstem reticular formation were examined. The results indicate that ATP facilitated the sensory system, cytochrome C facilitated the motor system and meclofenoxate and CDP-choline acted on both systems, but meclofenoxate had activity more like ATP, and CDP-choline had activity more closely allied to that of cytochrome C. PMID- 6254901 TI - Autoradiographic localization of serum retinol-binding protein receptors on the pigment epithelium of dystrophic rat retinas. AB - The density and distribution of the retinal pigment epithelium membrane receptor for serum retinol-binding protein (RBP) was compared in young rats (28 days postnatal) and adult rats (7.5 months postnatal) afflicted with retinal dystrophy. Following an intravascular injection of 125I-labeled RBP (125I-RBP) complexed with prealbumin, the binding of 125I-RBP was analyzed by quantitative autoradiographic methods. As the course of the disease progressed, the pigment epithelium of the dystrophic retina underwent regional modification. Some areas remained unchanged, whereas others were grossly altered by vascular infiltration or by attenuation due to reduction in cell number. The basal infoldings of the pigment epithelium in young and adult rats exhibited nearly identical binding densities for 125I-RBP when unmodified cells were compared. In areas of severe disruption, the blood-retinal barrier was compromised, and the labeled protein diffused readily into the the neural retina. The results imply that the RBP receptors persist on the surface of unmodified pigment epithelial cells in adult dystrophic retinas in spite of the decrease in demand for retinol that accompanies the loss of photoreceptors. PMID- 6254902 TI - Influence of chlorpromazine on the rabbit electroretinogram. AB - In anesthetized albino or nonalbino rabbits, a 3 to 8 mg/kg IV injection of chlorpromazine did not affect a-wave amplitude of the electroretinogram (ERG). However, immediately after the injection of the drug, b-wave amplitude increased. The maximum increase occurred between 35 to 50 min, and the recovery time varied between 5 to 8 hr. Initial changes in the b-wave amplitude to some extent were affected by systemic changes in the blood pressure. However, the b-wave amplitude remained high for a long time after the blood pressure reached preinjection value, indicating a local effect of the drug. There was no change in a- or b-wave latencies. Although in vitro a large quantity of chlorpromazine can be localized in the melanin granules from pigmented rabbit retina, in vivo the ERG b-wave changes caused by the small intravenous dose of the drug were similar in both albino and nonalbino rabbits. PMID- 6254903 TI - The effect of thermal burns on the release of collagenase from corneas of vitamin A--deficient and controls rats. AB - A mild trauma in the form of a thermal burn was applied to corneas of vitamin A- deficient rats and their pair-fed controls. The control corneas routinely showed rapid re-epithelialization without stromal changes. The corneas of deficient rats recovered more slowly, frequently exhibiting stromal edema, leukoma, and sometimes ulceration. Because collagenase is thought to initiate collagen destruction in corneal ulceration, the relationships among vitamin A status, severity of trauma, and collagenase levels were determine. Mild thermal burns were found to cause corneas from less severely deficient rats to ulcerate rarely but no release increased levels of collagenase, mainly on the first day of culture, as in the case of nonburned, severely deficient rats. Comparable burns of corneas of pair-fed control rats resulted in no ulceration and in very little collagenase release. Severe burns of either pair-fed control or normal rat corneas caused ulceration and collagenase release, but collagenase activity was maximal on the second and third days of culture. Differences in vitamin A status at time of burning gave rise to different patterns of collagenase. By following the development of the vitamin deficiency, it was determined that little active collagenase is released after mild burns of corneas in animals in the pre--weight plateau stage but that much more active enzyme is released when animals are in weight plateau or 5% weight loss stages. Studies of the effect of recovery from vitamin A deficiency on the response to mild thermal burn indicated that the longer the interval between feeding vitamin A and the burn, the lower the postburn level of collagenase in the day 1 medium. Thus it would appear that restitution of vitamin A status decreased the level of active collagenase after the mild thermal burn. The system developed here can be used to study the biochemical basis for ulceration in vitamin A deficiency, and the possibility exists that the ulceration characteristic of keratomalacia in people can be initiated by an environmental trauma. PMID- 6254904 TI - Replication of acute hemorrhagic conjunctivitis viruses in conjunctival-corneal cell cultures of mice, rabbits, and monkeys. AB - Acute hemorrhagic conjunctivitis (AHC) viruses--enterovirus type 70 (E70), and coxsackie-virus type A24 (CA24)--infect the superficial cells of the conjunctiva and cornea. We examined the growth of several E70 and CA24 isolates in monkey, rabbit, and mouse conjunctival and corneal (C/C) cells. We found that E70 isolates grew well in monkey (10(6.5) TCID50/ml), rabbit (10(4.5) to 10(5.5) TCID50/ml), and mouse (10(3.5) to 10(6.0) TCID50/ml) C/C cultures and caused cytopathic effects (CPE). In contrast, CA24 isolates replicated well and caused CPE only in monkey C/C cultures (10(6.5) TCID50/ml). These results show that E70 isolates grow readily in monkey, rabbit, and mouse C/C cells whereas CA24 isolates replicated in monkey C/C cells only. This finding is consistent with the suggestion that a lower animal reservoir may be a source of human infection by E70. These cell culture systems may be useful for studying virus-cell interactions and host defenses operating at the surface of the eye and for evaluating the feasibility of prophylactic or therapeutic use of interferon, interferon inducers, and/or antibody for controlling AHC virus infections. PMID- 6254905 TI - Selected hormone sensitivities of several transplantable T-cell lymphomas. AB - Ten T-cell lymphomas induced in 10 C3H mice with Gross' MuLv were established as transplantable tumor lines in syngeneic mice. The responses of these lines to cortisone, histamine, norepinephrine, and prostaglandin E1 were assessed after varying times in passage. Distinct and distinguishing sensitivity profiles were revealed. PMID- 6254906 TI - Biologial effects of the human complement fragments C5a and C5ades Arg on neutrophil function. PMID- 6254907 TI - The ethics advisory board & the right to know. PMID- 6254908 TI - Rotavirus in newborn nurseries: negative results from Honolulu and the New Hebrides. PMID- 6254909 TI - The chief scientist reports...human cytomegalovirus. PMID- 6254910 TI - Juvenile nasopharyngeal angiofibroma: control rates and treatment costs. PMID- 6254911 TI - [Experimental and clinical experiences with the synthetic skin cover of polyvinylalcohol-formaldehyde foam (PVA)]. AB - Animal experimental research and clinical experience in polyvinylalcohol formaldehyde foam (PVA) as a temporary skin cover: The usefulness of PVA as a temporary skin cover of burns and infected wounds was studied in animals. On the back of 20 pigs full thickness burns were produced and wounds were infected, then examined macroscopically, histologically and bacteriologically over a period of 18 days. PVA showed a better wound cleansing, a significantly reduced bacterial flora and a more rapid growth of the epithelium in comparison with three other materials. The clinical use of PVA in the treatment of compound fractures with a severe damage of soft tissue, of infected wounds and of burns also demonstrated a quick cleansing of the wound and an induction of a dense and vascularised granulation tissue. Thus considerable infections could be avoided and early grafting was possible. PMID- 6254912 TI - [The glucagon syndrome]. AB - Although the features of the glucagonoma syndrome had been described in isolated reports since 1942, this potentially curable condition has only recently been adequately defined. In 1974, MALLINSON collected nine cases and described the association of a peculiar skin rash with glucagon-secreting tumors of the pancreas. The typical skin rash, necrolytic migratory erythema, is accompanied by other disturbances including weight loss, anaemia, glossitis, cheilitis angularis, psychiatric symptoms. Diabetes is not a prominent feature, and the impairment of glucose tolerance can indeed be very slight. Up to 1979, about 50 cases have been reported. More than half of these patients had malignant tumors. The authors report on a 67-year-old man in whom a glucagonoma in the tail of the pancreas has been resected with apparent cure. The almost complete disappearance of the skin rash within three weeks of extirpation of the tumor has been most impressive. In June 1979 a similar tumor has been operated by one of the authors in a 60-year-old man. In this instance the tumor was located in the pancreatic corpus and could be radically resected by left-sided pancreatectomy. PMID- 6254913 TI - [Pleomorphic adenoma of the breast]. AB - The pleomorphic adenoma (mixed tumor) of the mammary gland is a rare benign tumor. Clinically, mammographically and histologically it can, on the basis of a quick-biopsy examination, be confounded with a carcinoma. We relate on a case of our own where the diagnostic difficulties conducted to an inadequate amputation of the mammary gland. PMID- 6254914 TI - [Soft tissue sarcoma of the limbs]. AB - 24 cases of soft tissue tumors treated during the last 10 years are analysed. Therapeutical results and a review of the literature are presented. Survival of patients with these types of tumors is very limited. Two points have to be emphasized. --Exact histological diagnosis, large surgical resection at distance of the neoplasm, done by an experienced surgeon give the best chances of good results. In many cases this means heavy surgery and severe functional loss. --The future will surely bring better treatment for these still poorly known tumors. Perfect knowledge of the topography of the neoplasm is necessary to perform surgery in best conditions. Chemotherapy and radiotherapy should be tested on larger series of cases to prove their efficiency. PMID- 6254915 TI - [Survival following surgery for bronchopulmonary cancer. Results after five years]. AB - The authors study the actuarial survival of 253 primary bronchopulmonary cancers operated in Geneva between 1967 and 1976. The overall operative mortality was 9.88%. The overall survival of resections alone was 26.6% at 5 years. The small size of the tumor, the absence of mediastinal extension and an epidermoid histology are the best survival rate factors: 43.2% of stage I cases survive at 5 years against 4.86% of stage III cases. The accidental discovery of as asymptomatic tumor gives a hope of survival of 43.9% at 5 years. Yet again this demonstrates the importance of mass screening by radiophotography. Surgery thus maintains its central role in the treatment of this disease, whilst chemo-, radio and immunotherapy have not yet revealed their full possibilities. PMID- 6254916 TI - [Small cell bronchus carcinoma: surgery or not?]. AB - According to literature the operability rate of small cell carcinoma of the bronchi varies from 6 to 26%. Out of this group of patients the 5-year survival rate is 0--5%. During the 8 years from 1965 to 1973 we observed 65 patients suffering from small cell bronchial carcinoma. All were men. The average age was 56.5 years. Out of this group of 65 patients 13 underwent operations. In 7 cases pneumonectomy, in 1 case lobectomy were performed. 3 patients became radical pneumonectomy. In 2 cases thoracotomy was performed. On the average the operated patients survived for 6.1 months. Out of the 13 patients 12 died during the first year and one patient survived 2 years after the operation. Out of the 52 patients who were found to be inoperable 42 had radiotherapy. In 2 patients additional chemotherapy was given. In the group of 52 patients, 58% died during the first 6 months and 85% died during the first year after diagnosis. 3 patients survived 13, 14 and 15 months respectively and one patient died 35 months after diagnosis. We come to the conclusion that surgery has not brought any advances in the treatment of this tumour. Our bad experience is shared by most authors. Indications for surgical treatment of this tumour therefore are extremely limited. PMID- 6254917 TI - [Intracellular and extracellular acid mucopolysaccharides in human bronchus carcinoma and lung metastases - prognostic parameters?]. AB - Local cellular and extracellular (acid mucopolysaccharide) reactions in human lung cancers and metastases - prognostic parameters? The role of immunologic reactions in human malignant tumors is still unsettled. In the work presented, 72 primary lung cancers and 17 pulmonary metastases of 8 different organs of origin were studied with histochemical techniques for cellular infiltrates (eosinophils and macrophages) and extracellular acid mucopolysaccharides (AMPS). The results showed a positive correlation between eosinophils and macrophages and a negative correlation between cellular reactions and the deposition of AMPS. The clinical course of radically operable patients with primary lung cancer 2 to 3 1/2 years after operation showed that patients with the reactive pattern "strong local eosinophilia, no AMPS deposition" had the best prognosis with 12 of 14 patients free of tumor. Of the patients with the same tumor stage, but lacking local eosinophilia, more than half died from the tumor or had generalized metastases within the same period. The most frequent pattern in patients with pulmonary metastases was "no local eosinophilia, strong AMPS reaction". These observations suggest that cellular reactions in radically operable primary lung cancer express immunologic responses. These are often absent in metastases. PMID- 6254918 TI - Physiologic and genetic alterations in human red cell DPGM. AB - Erythrocyte 2,3-diphosphoglycerate levels are determined principally by a single molecule which has both diphosphoglycerate mutase (DPGM) and diphosphoglycerate phosphatase activities. An antiserum containing precipitating antibodies against this molecule was used to measure its amount in red cells from normal controls, from subjects with hypothyroidism or hyperthyroidism, and from a Japanese proband who has hemolytic anemia attributed to heterozygosity for a genetic variant. The amount of DPGM in normal adult erythrocytes is 0.98 +/- 0.014 mg/gm Hb. Slightly increased amounts are found in normal cord blood and in subjects with hyperthyroidism. Hypothyroid subjects have a significantly decreased concentration of DPGM, 0.82 +/- 0.06 mg/gm Hb. Restoration of euthyroid status during treatment results in a return of DPGM amounts to normal. The red cells of the Japanese subject contained 0.67 mg/gm Hb of DPGM as measured by immunoprecipitation. PMID- 6254920 TI - Pyrimidine 5'-nucleotidase deficiency: studies of five cases in two Japanese families. AB - Two new families with red cell pyrimidine 5'-nucleotidase (P5N) deficiencies were found in Japan. The enzyme activities were 4.8% in case 1 and 9.7% in case 2. The propositi showed characteristic hemolytic anemia with market basophilic stippling, increased reduced glutathione content and accumulation of pyrimidine nucleotides in the red cell. High Michaelis constants for cytidine monophosphate, normal thermostability, abnormal optimum pH in both cases, and normal electrophoretic mobility in case 1 and slower mobility in case 2 were shown, suggesting that the cause of P5N deficiency, at least in these cases, is due to the structural gene mutation. PMID- 6254919 TI - Erythrocyte disorders of purine and pyrimidine metabolism. AB - The maturing reticulocyte degrades ribosomal RNA to constituent ribonucleoside phosphates. Guanosine ribonucleotides are retained only in small amounts and pyrimidine ribonucleotides only in trace quantities. In the mature erythrocyte more than 97% of total nucleotides are the interconvertible adenosine mono-, di-, and triphosphates. High energy ATP fuels most of the reactions required to sustain viability. Unable to synthesize adenosine phosphates from small precursor molecules, the red cell relies on certain salvage pathways to replenish its losses from the adenosine phosphate pool. The most important of these involve adenosine. Adenylate kinase deficiency, when severe, is associated with nonspherocytic hemolytic anemia. A genetically-determined deficiency of pyrimidine 5'-nucleotidase prevents the normal dephosphorylation of pyrimidine ribonucleotides, and hence is characterized by the unique accumulation of pyrimidine phosphates intracellularly. Other features are chronic hemolytic anemia, splenomegaly, and a profound increase in basophilic stippling on the stained blood film. The syndrome is transmitted as an autosomal recessive disorder. A similar syndrome is found in severe lead poisoning as a consequence of nucleotidase inhibition by lead. An inherited, dominantly transmitted hemolytic anemia associated with low red cell ATP and a 45-70 fold increase in the enzymatic activity of adenosine deaminase has also been documented. The undefined molecular lesion appears to involve overproduction of an entirely normal enzyme protein. Severe deficiency of either of two sequential enzymes of purine metabolism, adenosine deaminase anemia, but by excessive accumulations of deoxyribonucleotides within red cells and lymphocytes. The clinical counterpart of each is a severe immunodeficiency state secondary to lymphopenia and lymphocyte dysfunction. Certain other rare clinical syndromes involving disturbed nucleotide metabolism also are detectable by red cell assay procedures. PMID- 6254921 TI - Some problems in enzyme determination in red cells mainly due to the membrane structure. AB - For the enzyme assay in red blood cells, three problems related to membrane structure were examined. (1) It was difficult to get full activity of membrane enzymes, especially ATPases. The effects of various buffers and substrates and conditions of preservation were examined. (2) During preservation of blood, phosphofructokinase (PFK) decreased most among 15 enzymes including all glycolytic enzymes. This decrease was prevented by the addition of adenine and inosine which produce ATP inside the cells. After hemolysis, PFK decreased most rapidly, too. ATP prevented the inactivation effectively. (3) after centrifugation, even according to Murphy's method, pyruvate kinase decreased most in the lowest layer of stacked erythrocytes. This might be due to the effect of centrifugation. PMID- 6254922 TI - Membrane protein phosphorylation and protein kinases in normal and hereditary spherocytosis red cells. AB - Membrane protein phosphorylation by protein kinases in normal red cells takes place mainly on band 2 at the basal activity, and on bands 1 and 2.1 in the presence of cyclic 3':5'-adenosine monophosphate. Calcium precipitates preferentially bands 1 and 2.1 on extracted membrane proteins, and inhibit the membrane protein phosphorylation. Phosphorylation of endogeneous membrane proteins is diminished in red cells of some patients with hereditary spherocytosis (HS), partly corresponding reciprocally to MCHC, % spherocytes and reticulocytosis in peripheral blood of these patients, although the enzymatic activities of glyceraldehyde-3-phosphate dehydrogenase as a marker of the inner surface of red cell membranes are maintained normally in these red cells. The pattern of membrane protein fractions in HS red cells as endogeneous substrates for phosphorylation reactions is almost identical to that in normal red cells. Activities to phosphorylate casein or histone as exogeneous substrates are normal in HS red cell ghosts. PMID- 6254923 TI - The effects of adriamycin (doxorubicin HCl) on human red blood cells. AB - We have studied the effects of adriamycin (doxorubicin HCl) on human red blood cells. The peroxidizing effect of adriamycin on the thiols of red cell constituents resulted in decreased glutathione stability, and oxidation of hemoglobin and membrane protein components 1, 2, and 3, forming large molecular weight complexes. Membrane lipids were also peroxidized. Adriamycin itself did not inhibit the enzymes of the reductions system (glucose-6-phosphate dehydrogenase, 6-phosphogluconic dehydrogenase, glutathione reductase, glutathione peroxidase, catalase, superoxide dismutase) of the red cells. Because adriamycin has the potential of inhibiting ATPase, including both Na-K-dependent ATPase and ouabain insensitive ATPase, at concentrations not inhibitory to other enzymes, the net sodium content increased, and potassium content decreased after incubation of red cells with adriamycin at high concentrations. The experimental results described with adriamycin may serve as a model for the possible mechanism of cardiotoxicity observed in its clinical use, and also explain the potential hemolyzing effect on red cells. There was greater oxidizing effect on glucose-6 phosphate dehydrogenase (G-6-PD) deficient than on normal erythrocytes. It is suggested that adriamycin be used with caution in individuals with G-6-PD deficient red cells. PMID- 6254924 TI - Genetic variants of red cell enzymes as potential anthropological markers in the Western Pacific. AB - During the population genetic surveys of the aboriginal Negrito groups of the Philippines, "rare" variants of carbonic anhydrase-1 (CA1), adenylate kinase (AK) and esterase D (ESD) were discovered with remarkably high frequencies. The variant CAS1 isozyme discovered among the Mamanwa tribe of northeastern Mindanao was electrophoretically indistinguishable from the "Guam" variant. Subsequent study of peptide mapping and amino acid analysis showed that they are in fact identical. The frequency of the variant allele was estimated at 0.20-0.25. The AK variant had an estimated frequency of 0.07 among the Aeta of Luzon. The fact that these variants occur sporadically in wide areas in the western Pacific suggests that they have been spread by gene diffusion from the aboriginal populations of this area, from which the present Negrito probably are derived. PMID- 6254925 TI - Localization of AT-clusters in normal mouse chromosomes by netropsin prefixation treatment in vitro. PMID- 6254926 TI - Light and electron microscopical combined staining by immunohistochemical and enzyme histochemical methods using rat prolactin-secreting pituitary tumours. AB - Combined immunohistochemical staining (IHCS) and enzyme histochemical staining (EHCS) methods for light microscopy (LM) and electron microscopy (EM) are reported, using oestrogen-induced rat pituitary tumours. For LM, combined staining for alkaline phosphatase and acid phosphatase by EHCS, using the azo dye method, and for prolactin and ACTH by IHCS, using the enzyme-labelled antibody method, gave the best results on 1 microgram glycol methacrylate sections. For EM, combined staining by EHCS on 30 microgram tissue sections followed by IHCS for prolactin on ultrathin Epon sections (enzyme-labelled antibody method) provided acceptable results. By these combined staining methods, the neoplastic prolactin cells were shown to have close affinity to rich alkaline phosphatase positive capillaries and to possess an alkaline phosphatase-positive cell membrane. Furthermore, they revealed acid phosphatase-positive lysosomal and secretory granules. These combined staining methods may be valuable in studies on the actual functional status of cells. PMID- 6254927 TI - A critique of the contributions of immunoperoxidase cytochemistry to our understanding of pituitary cell function, as illustrated by our current studies of gonadotropes, corticotropes and endogenous pituitary GnRH and TRH. AB - The peroxidase-antiperoxidase technique has been used to study sites of pituitary hormone storage and binding. Some recent findings from our laboratory show that the technique can make intriguing contributions to our understanding of pituitary cell function. In serial, ultra-thin sections, one can identify two or three hormones in a given cell. During pre-pubertal development, gonadotropes may contain adrenocorticotropin immunoreactivity. Brain releasing hormones may be stored or sequestered in granules of cells they stimulate. This report includes a discussion and critique of our recent findings and interpretations which must be considered before one draws any conclusions about their biological significance. PMID- 6254928 TI - Immunofluorescent demonstration of myeloperoxidase of phi bodies and rods in leukaemic leucocytes. AB - Previous studies employing enzyme histocytochemical methods based on the catalysis of the peroxidation of 3,3'-diaminobenzidine (DAB) demonstrated the presence of hydroperoxidase activity in phi bodies and rods of immature leucocytes of patients with active acute myelogenous leukaemia. It could not be determined from these studies whether the DAB oxidation product was demonstrating a single hydroperoxidase, catalase or myeloperoxidase, or both. In the present study, immunofluorescence techniques for the two hydroperoxidases were applied in an attempt to identify this activity specifically. The results obtained indicate that myeloperoxidase is present in the phi bodies and rods, and that this enzyme may be the major or the only hydroperoxidase present. Its activity could account for the peroxidation of DAB under conditions which are more favourable for the demonstration of catalase. PMID- 6254929 TI - Dehydrogenase activity and loss of formazan from tissue sections. AB - Formazans can be lost from tissue sections when the incubation medium is removed at the end of a dehydrogenase reaction. The loss is not uniform and will clearly affect the interpretation of results. This suggests that both the qualitative evaluation of the reaction and the measurement of enzyme activity should be made at the time of incubation. PMID- 6254930 TI - Immunohistochemical identification of cells in the pars distalis of the pituitary of the lizard Anolis carolinensis. AB - Immunocharacteristics of the pars distalis cells of the pituitary of the male lizard A. carolinensis are determined by employing the immunoperoxidase technique with antisera to mammalian pituitary hormones. On the basis of their immunoreactivity, 5 different cell types with characteristic anatomical distribution are recognized. ACTH cells are found in the rostral half of the pars distalis, and PRL cells in the rostral two thirds of the pars distalis. GH and TSH cells are located in the caudal half of the pars distalis. GTH cells are distributed throughout the gland. When consecutive sections are stained with antiserum to ovine FSH or its beta-subunit and to ovine LH, the same cells show immunoreactivity to all the three antisera. None of the GTH cells show positive immunoreactivity to ovine beta-LH antiserum. The results suggest the existence of one gonadotropic cell type in the pituitary of this lizard. PMID- 6254931 TI - Adenosine triphosphatase localization in the branchial heart of Sepia officinalis L. (Cephalopoda). AB - Sodium- and potassium-dependent adenosine triphosphatase (Na+--K+-ATPase) is demonstrated in the branchial heart of Sepia officinalis L. by biochemical, cytochemical and autoradiographical methods. The biochemical data indicate the presence of Na+--K+-ATPase, shown by potassium and magnesium dependency and inhibition by ouabain. Cytochemically and autoradiographically, the enzyme is localized in the sarcolemma of the muscle cells. The positive reaction of the transparent cells (type I cells) is due to activity of alkaline phosphatases. The dark cells (type II cells) react negatively. In addition to the Na+--K+-ATPase, a magnesium-activated adenosine triphosphatase (Mg2+-ATPase) and a bicarbonate stimulated ATPase (HCO3(-)-ATPase) are localized in the mitochondria. PMID- 6254933 TI - [The diagnosis of nasopharyngeal carcinoma (author's transl)]. AB - Nasopharyngeal carcinoma (NPC) is etiologically closely connected to the Epstein Barr virus. NPC is the only carcinoma in man that can be diagnosed serologically. In the serum of patients with NPC characteristic antibody titres of certain viral antigens can be demonstrated during the disease. Conclusions regarding the success of treatment and on possible relapse can be deduced from these antibody titres. Criteria of histological differention for NPC prognosis are described, and the possible mode of infection is discussed. Since the disease also occurs in adolescents the treatment of a typical case of NPC is described. PMID- 6254934 TI - A comparison of continuous and discrete foreign gas VA/Q distributions. AB - Estimates of ventilation-perfusion ratio (VA/Q) distributions from foreign gas infusions have utilized a discrete lung model that constrains all alveoli to have 1 of 50 specified VA/Q. In contrast, distribution estimates based on a continuous model allow alveoli to have any VA/Q and can be derived directly from foreign gas data or by transforming distributions derived using the discrete model. We have compared analytically and empirically the properties of distributions based on these two models. Unlike the discrete model, the shape of distributions obtained from the continuous model are insensitive to changes in the VA/Q used in their calculation. Perfusion distributions found from the discrete model using VA/Q values evenly spaced on a logarithmic scale resemble ventilation distributions derived from the continuous model. In contrast, by use of VA/Q evenly spaced on a linear scale, perfusion distributions derived from either model have a similar shape. We concluded that physiological inferences derived from distribution shapes may vary according to the model employed. However, those based upon cumulative perfusion or distribution moments are invariant. PMID- 6254932 TI - Metabolic zonation in thioacetamide-induced liver cirrhosis. AB - After TAA administration to rats a central part may be distinguished histochemically from a marginal part in most of the cirrhotic nodules. The centre is characterized by a high glycogen content and by high activity of phosphorylase, G6Pase and SDH; the maxima of which are situated around the larger blood vessels. The vasculatory periphery, however, shows moderate G6PDH-activity. The marginal parts of the nodules are poor in glycogen and possess only weak G6Pase and phosphorylase activity, whereas high SDH- and G6PDH-activity can be demonstrated here. This distribution pattern leads to the conclusion that the larger blood vessels in the centre of the nodules are themselves the terminal afferent vessels. Thus the centre of the nodule corresponds to periportal zone 1, while G6PDH-activity marks the area corresponding to zone 3. The fact that the marginal parts of the nodules are marked by high SDH- but weak G6Pase-activity is interpreted as the result of a preferential arterial supply to this parenchymal part. The high G6PDH-activity of the marginal part is seen in context with the regeneration processes. In all animals single nodules could be found with a high glycogen content and extremely high G6PDH-activity. This loss of heterogeneity is interpreted as a first step in the direction of malignancy. PMID- 6254936 TI - Reactivity and contractility of rat main pulmonary artery to vasoactive agents. AB - In vitro studies were undertaken to determine the reactivity and contractility of the rat main pulmonary artery (RPA) to some selected vasoactive agents. Oxytocin was found to be inactive RPA exhibited a poor responsiveness to vasopressin, acetylcholine, histamine, and bradykinin. Prostaglandins B2 and E2, K+, angiotensin, sympathomimetic agents (epinephrine and isoproterenol), 5 hydroxytryptamine (5-HT), and [Ca2+]0 were found to produce, consistently, potent and concentration-related contractions of the RPA. Pulmonary arterial strips that were precontracted with 5-HT responded with relaxations to isoproterenol in low concentrations and with contractions in high concentrations. Blockade of isoproterenol-induced relaxation by propranolol provides evidence for the existence of specific beta-adrenoceptors in RPA. The selective antagonism of contractile responses induced by epinephrine, 5-HT, acetylcholine, and histamine by phentolamine, methysergide, atropine, and pyrilamine, respectively, provides evidence for the occurrence of specific alpha-adrenergic, "D"-serotonin as well as some cholinergic (muscarinic) and H1-histamine receptors in the RPA. PMID- 6254935 TI - Evidence for alpha-adrenergic innervation of the isolated canine thoracic duct. AB - The excitatory innervation of isolated thoracic duct segments was studied using tissue bath techniques. No spontaneous activity was present in longitudinal or helical strips obtained from a portion of the thoracic duct cephalad to the hilum of the lung. Norepinephrine (10(-8) to 10(-5) M) and tyramine (3 x 10(-5) M) produced contractions that were antagonized by phentolamine (2 x 10(-5) M) and phenoxybenzamine (10(-7) M). Acetylcholine (10(-7) to 10(-4) M) produced contractions that were antagonized by atropine (5 x 10(-9) M). Thoracic duct strips also contracted in response to field electrical stimulation, and maximal responses were obtained with a stimulus of 15 V, 15 Hz, and 1-ms pulse duration. These electrically induced contractions were abolished by tetrodotoxin (5 x 10( 7) M), phentolamine (2 x 10(-5) M), phenoxybenzamine (10(-7) M), and guanethidine (3 x 10(-6) M), but not by atropine (10(-6) M). We conclude that smooth muscle of the canine thoracic duct contains alpha-adrenergic and acetylcholine receptors, both of which cause contraction when stimulated. However, only the alpha receptors appear to be innervated. PMID- 6254937 TI - Changes in beta-adrenergic responsiveness of rats during chronic cold exposure. AB - Administration of isoproterenol (50 micrograms/kg sc) to rats that had been exposed to cold (6 degrees C) for 10, 15, and 25 days was accompanied by a greater increase in tail skin and colonic temperatures than in controls kept at 25 degrees C. Administration of isoproterenol (8 micrograms/kg sc) to cold treated rats (1, 3, 5, 7, 14, and 28 days) increased heart rates above that of controls. However, resting unstimulated heart rates of cold-treated rats were also increased above that of controls after 1, 3, 5, and 7 days of cold exposure but were not different from controls after 14 and 28 days. Cold exposure also led to time-dependent increases in the weights of heart, adrenals, and interscapular brown fat. Thus, chronic exposure of rats to cold is accompanied by an increase in responsiveness of both heart rate and tail skin and colonic temperatures to beta-adrenergic stimulation. The results also suggest that increases in responsiveness to a beta-adrenergic agonist may not occur at the same time for the different beta-adrenergic-mediated metabolic and cardiovascular responses in cold-treated rats. PMID- 6254938 TI - Isolation of a paramyxovirus from the cerebrospinal fluid of a dog with posterior paresis. AB - A paramyxovirus was isolated from cerebrospinal fluid of a dog with a history of incoordination and posterior paresis. The virus apparently was not related to canine distemper virus (CDV), considering the lack of virus neutralization with CDV-specific antibody, negative immunofluorescence with CDV-specific conjugate, and avirulence for ferrets. The virus was antigenically related to a prototype strain of canine parainfluenza virus, as determined by positive immunofluorescence with canine parainfluenza virus-specific conjugate and virus neutralization tests. PMID- 6254939 TI - In defense of Leukoassay F. PMID- 6254941 TI - Placental lesions caused by pseudorabies virus in pregnant sows. AB - Pathologic and viral investigations were done on 13 fetal placentas and 23 aborted fetuses associated with naturally occurring pseudorabies in swine. Of the 13 fetal placentas examined, 7 (53.8%) had various degrees of necrotizing placentitis. The lesions were characterized by coagulative necrosis of the chorionic fossae and by intranuclear inclusions in degenerating trophoblasts and occasionally in mesenchymal cells. In addition, a mild inflammatory cell reaction was observed in the mesenchyma. Numerous viral particles, ultrastructurally indistinguishable from herpesvirus, were observed by electron microscopy in the affected chorionic membrane. Large aggregates of herpesvirus virions were demonstrated in the nucleus and cytoplasm of degenerated trophoblasts and mesenchymal cells. Of the 23 aborted fetuses examined, 22 (95.6%) had typical coagulative necrosis in the liver, spleen, adrenal glands, and visceral lymph nodes. Inclusions similar to those in the chorionic placenta were observed in the parenchymal cells of those organs, on the margins of necrotic areas. Pseudorabies virus was isolated from various organs of the aborted fetuses, but virus isolation from the placentas was not attempted. In a survey of 52 affected sows, sera from 49 (94.2%) neutralized the isolated virus. The findings indicated that the placental lesions caused by the virus were primary. The study also indicated the merit of routine examination of aborted fetal placentas and fetuses for diagnosis of pseudorabies. PMID- 6254940 TI - Prevalence of bovine leukemia virus antibody in seven herds of Holstein-Friesian cattle. AB - Sera from 959 Holstein-Friesian cattle in 7 herds were tested for antibody to bovine leukemia virus, using the agar gel immunodiffusion test with glycoprotein antigen. Seropositive cattle were found in 6 herds; 120 (12.5%) were reactors. In 1 of the herds, the prevalence of seropositive cattle was significantly greater in purebred than in grade cows. Purebred cows raised on the premises and an overall antibody prevalence similar to purchased purebred cows. Purebred cattle more than 2 years old had a significantly greater prevalence of reactors than younger cattle. There was no difference in prevalence by sex. PMID- 6254943 TI - Vascular compartments and territories of tympano-jugular glomic tumors. PMID- 6254942 TI - In vitro evaluation of LY127935 (6050S) compared with cefotaxime, eight other beta-lactams and two aminoglycosides. PMID- 6254944 TI - Plasmid replication functions: two distinct segments of plasmid R1, RepA and RepD, express incompatibility and are capable of autonomous replication. AB - The genetic determinants for replication and incompatibility of plasmid R1 were investigated by gene cloning methods, and three types of R1 miniplasmid derivatives were generated. The first, exemplified by plasmid pKT300, consisted of a single BglII endonuclease-generated deoxyribonucleic acid fragment derived from the R1 region that is located between the determinants for conjugal transfer and antibiotic resistance. Two types of miniplasmids could be formed from PstI endonuclease-generated fragments of pKT300. One of these, which is equivalent to miniplasmids previously generated from plasmids R1-19 and R1-19B2, consisted of two adjacent PstI fragments that encode the RepA replication system of plasmid R1. The other type contained a segment of R1, designated the RepD replication region, that is adjacent to the RepA region and that has not been identified previously as having the capacity for autonomous replication. Plasmid R1, therefore, contained two distinct deoxyribonucleic acid segments capable of autonomous replication. The RepA-RepD miniplasmid pKT300 had a copy number about eightfold higher than that of R1 and hence lacked a determinant for the regulation of plasmid copy number. Like R1, it was maintained stably in dividing bacteria. RepA miniplasmids had copy numbers which were two- to fourfold higher than that of R1 (i.e., which were lower than that of pKT300) and were maintained slightly less stably than those of pKT300 and R1. The RepD miniplasmid was not maintained stably in dividing bacteria. Previous experiments have shown that incompatibility of IncFII group plasmids is specified by a plasmid copy control gene. Despite the fact that RepA miniplasmids of R1 were defective in copy control, they nevertheless expressed incompatibility. This suggests that two genes are responsible for plasmid copy control, one that specifies incompatibility and is located on RepA miniplasmids and another that is located outside of, but adjacent to, the RepA replication region. Hybrid plasmids composed of pBR322 and one PstI fragment from the RepA region, P-8, exhibited incompatibility towards R2 and RepA miniplasmids but not the RepD miniplasmid, whereas hybrids composed of pBR322 and the PstI fragment of the RepD region, P-3, exhibited incompatibility towards R1 and the RepD miniplasmid but not RepA miniplasmids. These results indicate that the two replication systems are functionally distinct and that, although the RepA system is the principal replication system of R1, the RepD system also plays a role in the maintenance of this plasmid. PMID- 6254945 TI - Myceloid growth of Arthrobacter globiformis and other Arthrobacter species. AB - Transitory myceloid growth occurs in certain complex media with Arthrobacter globiformis strain ATCC 8010. This type of growth, however, was not observed in a medium which contained an array of metal ions but did not contain agents able to complex metal ions. Addition of metal-complexing agents to this medium caused an interruption in the life cycle of strain 8010 so that growth occurred only as the myceloid form. It appeared that manganese was the critical metal that was removed by the metal-complexing agents. During growth, the myceloid cells started to fragment, but wall septation was incomplete. A. globiformis strain ATCC 4336 and several other Arthrobacter species and soil isolates, but not Arthrobacter crystallopoietes, responded to metal-complexing agents as did strain 8010. Biotin and vitamin B12 were not involved in this myceloid growth. PMID- 6254946 TI - Genetic behavior of the methicillin resistance determinant in Staphylococcus aureus. AB - The cotransformation frequency of mecC5 with pur-102 using Staphylococcus aureus C5 deoxyribonucleic acid was found to be approximately 45%. However, in cotransduction studies, there was a 15% cotransduction of purine prototrophy and methicillin sensitivity but, in the reciprocal cross, no purine-prototrophic plus Mecr cotransductants were obtained (frequency less than 0.06%). The data support the hypothesis that the mec determinant resides on an inserted deoxyribonucleic acid sequence in S. aureus and that there is no allelic equivalent in sensitive cells. PMID- 6254947 TI - Polymyxin B release of unnicked cholera toxin subunit A. AB - Polymyxin B treatment of Vibrio cholerae 569B grown with or without lincomycin released an extracytoplasmic pool of free unnicked cholera toxin subunit A. PMID- 6254948 TI - The ebg operon consists of at least two genes. AB - The ebg operon of Escherichia coli includes a second gene designated ebgB. The ebgB gene product is a 79,000-molecular-weight protein and is expressed coordinately with the ebgA gene product, ebg beta-galactosidase. Insertion of the transposable elements Tn5 and Tn9 into ebgA eliminates the expression of ebgB, suggesting that ebgB is distal to ebgA. Ultraviolet light mapping confirms that gene order. The function of the ebgB gene product is unknown. PMID- 6254949 TI - Formation of a lambda (Tn10) tyrR+ specialized transducing bacteriophage from Escherichia coli K-12. AB - The transposon Tn10, coding for resistance to tetracycline, was inserted close to the tyrR+ gene at min 28 on the Escherichia coli chromosome. The homology between this transposon and a lambda (Tn10) phage was employed to direct integration of lambda close to tyrR+ with subsequent isolation of a lambda (Tn10) tyrR+ transducing phage. Results of restriction endonuclease analysis of the transducing phage are presented. PMID- 6254950 TI - Quantitative measurements of proton motive force and motility in Bacillus subtilis. AB - The protein motive force of metabolizing Bacillus subtilis cells was only slightly affected by changes in the external pH between 5 and 8, although the electrical component and the chemical component of the proton motive force contributed differently at different external pH. The electrical component of the proton motive force was very small at pH 5, and the chemical component was almost negligible at pH 7.5. At external pH values between 6 and 7.7, swimming speed of the cells stayed constant. Thus, either the electrical component or the chemical component of the proton motive force could drive the flagellar motor. When the proton motive force of valinomycin-treated cells was quantitatively decreased by increasing the external K+ concentration, the swimming speed of the cells changed in a unique way: the swimming speed was not affected until about--100 mV, then decreased linearly with further decrease in the proton motive force, and was almost zero at about--30 mV. The rotation rate of a flagellum, measured by a tethered cell, showed essentially the same characteristics. Thus, there are a threshold proton motive force and a saturating proton motive force for the rotation of the B. subtilis flagellar motor. PMID- 6254951 TI - Respiratory systems and cytochromes in Campylobacter fetus subsp. intestinalis. AB - Cell suspensions of Campylobacter fetus subsp. intestinalis grown microaerophilically in complex media consumed oxygen in the presence of formate, succinate, and DL-lactate, and membranes had the corresponding dehydrogenase activities. The cells and membranes also had ascorbate-N,N,N',N'-tetramethyl-p phenylenediamine oxidase activity which was cyanide sensitive. The fumarate reductase activity in the membranes was inhibited by p chloromercuriphenylsulfonate, and this enzyme was probably responsible for the succinate dehydrogenase activity. Cytochrome c was predominant in the membranes, and a major proportion of this pigment exhibited a carbon monoxide-binding spectrum. Approximately 60% of the total membrane cytochrome c, measured with dithionite as the reductant, was also reduced by ascorbate-N,N,N',N'-tetramethyl p-phenylenediamine. A similar proportion of the membrane cytochrome c was reduced by succinate under anaerobic conditions, whereas formate reduced more than 90% of the total cytochrome under these conditions. 2-Heptyl-4-hydroxyquinoline-N-oxide inhibited reduction of cytochrome c with succinate, and the reduced spectrum of cytochrome b became evident. The inhibitor delayed reduction of cytochrome c with formate, but the final level of reduction was unaffected. We conclude that the respiratory chain includes low- and high-potential forms of cytochromes c and b; the carbon monoxide-binding form of cytochrome c might function as a terminal oxidase. PMID- 6254952 TI - Location of two relaxation nick sites in R6K and single sites in pSC101 and RSF1010 close to origins of vegetative replication: implication for conjugal transfer of plasmid deoxyribonucleic acid. AB - A nick-labeling method has been used to localize the relaxation complex nick sites in three plasmids (pSC101, RSF1010, and R6K) that differ markedly in their host range, deoxyribonucleic acid replication, and conjugal transfer properties. Single specific relaxation sites were located in pSC101 and RSF1010, but surprisingly two distinct sites could be identified in the bi-origin plasmid R6K. In all cases, relaxation nick sites, which are thought to be origins of plasmid conjugal transfer, were shown to be located near origins of vegetative replication. This result suggests a functional interaction between these two types of deoxyribonucleic acid loci, and we speculate here that application events initiated at origins of replication may constitute an integral part of the process of conjugal transfer of small plasmids among bacteria. Consistent with this proposal is the finding that inhibition of vegetative replication of the pSC101 and ColE1 plasmids results in a severe inhibition of their conjugal transfer ability. PMID- 6254953 TI - Some endocrine aspects of affective disorders. AB - While frank hypothyroidism can precipitate depression, most depressed patients are euthyroid. Nevertheless, there is evidence that a resilient HPT axis favors recovery from depression. Clearly small amounts of the thyroid hormones accelerate the antidepressant action of TCA, at least in women, and usually remedy TCA failure in both men and woman. Athough TRH appears to produce mood elevation in many kinds of patients as well as in normal subjects, this property cannot presently be exploited therapeutically. The present value of TRH in psychiatry is as a psychoendocrine diagnostic tool. Used in this way it has revealed a subpopulation of depressed patients and a subpopulation of alcoholic patients who show a blunted TSH response in the absence of usual endocrinological explanations. PMID- 6254954 TI - Ca2+-dependent protein phosphorylation and insulin release in intact hamster insulinoma cells. Inhibition by trifluoperazine. AB - Ca2+-dependent protein phosphorylation was studied in intact hamster insulinoma cells. Depolarizing concentrations of potassium which stimulate Ca2+ uptake and insulin release by these cells also increased phosphorylation of one peptide, Mr = 60,000 (P60). This was demonstrated by incubating 32P-labeled insulinoma cells in media containing 50 mM K+ followed by analysis of the cellular proteins by sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis and autoradiography. Potassium-induced phosphorylation of P60 was nearly half-maximal after 1 min and reached a plateau by 10 min. The enhanced 32P-labeling of P60 observed in the presence of 50 mM K+ was Ca2+-dependent since omission of extracellular Ca2+ or addition of the Ca2+ channel blocker alpha-isopropyl-alpha [(N-methyl-N-homoveratryl)-gamma-aminopropyl]3,4,5-trimethoxyphenylacetonitrile hydrochloride prevented the effect. Glucagon (3 microM), which stimulates insulin release in a cAMP-dependent manner, had no effect on P60 phosphorylation. A possible involvement of calmodulin was explored in studies using trifluoperazine. The Ca2+-dependent increase in phosphorylation of P60 was prevented by trifluoperazine. Moreover, Ca2+ influx-mediated insulin release and P60 phosphorylation were inhibited at nearly identical concentrations of trifluoperazine. Half-maximal inhibition of potassium-induced insulin release and P60 phosphorylation was seen at 2.6 microM and 2.5 microM trifluoperazine, respectively. The data are consistent with a sequence of events involving Ca2+ influx, phosphorylation of P60 by a calmodulin-dependent protein kinase, and resultant insulin secretion. PMID- 6254955 TI - Phosphorylation of smooth muscle myosin light chains by cAMP-dependent protein kinase. AB - The 20,000-dalton light chain of chicken gizzard myosin was phosphorylated in vitro by the cAMP-dependent protein kinase (ATP: protein phosphotransferase, EC 2.7.1.37) from bovine heart. The enzyme catalyzed incorporation of 1 mol of Pi/mol of light chain in a reaction that was completely dependent upon cAMP and independent of Ca2+. Two-dimensional peptide mapping of alpha-chymotryptic digests, as well as phosphoamino acid analysis of acid hydrolysates, were used to compare the site phosphorylated by cAMP-dependent protein kinase to that phosphorylated by turkey gizzard myosin light chain kinase. The results indicate that both enzymes phosphorylate the same serine residue. However, the light chains were a better in vitro substrate for myosin light chain kinase than for cAMP-dependent protein kinase. The amino acid sequence around the phosphorylated serine is characteristic of substrates of cAMP-dependent protein kinases. PMID- 6254956 TI - Activity in vitro of three replication origins of the antibiotic resistance plasmid RSF1040. AB - Replicating molecules of plasmid RSF1040, a deletion mutant of R6K, were synthesized in vitro and analyzed by electron microscopy. Initiation of replication occurs at three unique sites, ori alpha, ori beta, and ori gamma, within a 3900-base pair segment of the R6K genome. These sites are indistinguishable from the origins that are active in vivo. Frequencies of initiation at these three origins, however, are different from those observed in vivo. Replication proceeds unidirectionally in either direction from ori beta and ori gamma and in one direction from ori alpha. The replication terminus of the R6K genome is inactive in the in vitro system. PMID- 6254957 TI - Three origins of replication are active in vivo in the R plasmid RSF1040. AB - Replicating DNA molecules of RSF1040, a deletion derivative of the conjugative R plasmid R6K, are cleaved at a single site by the Eco RI restriction endonuclease. Microscopic analysis of Eco RI-cleaved RSF1040 replicative intermediates synthesized in vivo indicates that initiation of replication occurs at three unique sites, ori alpha, ori beta, and ori gamma. The relative frequencies of initiations at these three origins are different from those found in vitro. PMID- 6254959 TI - The arginines of cytochrome c. The reduction-binding site for 2,3-butanedione and ascorbate. AB - The reactions of both ferric and ferrous horse heart cytochrome c with 2,3 butanedione, pH 7.5, 0.05 M bicarbonate buffer, under a variety of solution conditions, have been examined using amino acid integrity as the primary criterion. The only observable structural alteration was the modification of both the arginyl side chains. The reaction profiles were found to be dependent upon the presence or absence of borate and ascorbate. The single-phased modification of the arginyl side chains in ferrocytochrome c in the absence of borate is rendered biphasic in the presence of borate (borate/reagent ratio of 0.04) through substantial lowering of the rate of reaction of one of the two arginyl side chains. The addition of ascorbate inhibits the reaction in a competitive manner, particularly of the arginyl side chain undergoing rapid modification in its absence. The reactivity of both arginyl side chains to reagent for the ferricytochrome was appreciably larger than for ferrocytochrome c. The addition of reagent to ferricytochrome c also reduces heme iron, which is discerned from the development of a native-like spectrum in the region 500 to 600 nm. The differences in the reactivities of the arginyl side chains to 2,3-butanedione in the two valence states of heme iron are the reflection of small, but definite, conformational differences at the two sites in the two valence states of the protein. The concurrent reduction of heme iron and the modification of the arginyl side chains localizes the reduction and the reaction site for 2,3 butanedione. The inhibition by ascorbate of the reaction of one of the two arginines also identifies the binding domain. Of the two arginines, Arg-38 is suggested to be the ascorbate-binding site. PMID- 6254958 TI - Hydrophobic regions function in calmodulin-enzyme(s) interactions. AB - Certain naturally occurring lipids (phosphatidylinositol, phosphatidylserine, arachidonic acid) and sodium dodecyl sulfate activate at least two calmodulin dependent enzymes, bovine brain 3':5'-cyclic nucleotide phosphodiesterase and chicken gizzard myosin light chain kinase in the absence of Ca2+. 2-p-Toluidinyl naphthalene-6-sulfonate (TNS), which is often used as a probe for hydrophobic groups of proteins, inhibits these two calmodulin-dependent enzymes. Kinetic analysis of inhibition of chicken gizzard myosin kinase by TNS revealed a competitive fashion against calmodulin-induced activation. The interaction between TNS and purified bovine brain calmodulin as demonstrated in the appearance of TNS fluorescence in the presence of 3 microM or more of calcium ion was not observed in the presence of 2 mM EGTA. This suggests that TNS is able to bind to calmodulin in the presence of Ca2+. Moreover, a calmodulin-interacting agent N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide suppressed the TNS fluorescence induced by complex formation with calmodulin in the presence of Ca2+. These results suggest that when Ca2+ binds to the high affinity sites of calmodulin, it induces a conformational change which exposes hydrophobic groups, and the calmodulin is then capable of activating calmodulin-dependent enzymes. We propose that hydrophobic properties of Ca2+-calmodulin are important for the activation of Ca2+-calmodulin-dependent enzymes. PMID- 6254961 TI - Role of heme in the synthesis of cytochrome c oxidase in Neurospora crassa. AB - The role of heme in the synthesis of cytochrome c oxidase has been investigated in the mold Neurospora crassa. Iron-deficient cultures of the mold have low levels of cytochrome oxidase and delta-aminolevulinate dehydratase, the latter being the rate-limiting enzyme of the heme-biosynthetic pathway in this organism. Addition of iron to the iron-deficient cultures results in an immediate increase in the levels of delta-aminolevulinate dehydratase followed by an increase in the rate of heme synthesis and cytochrome oxidase levels. The rate of precursor labeling of the mitochondrial subunits of cytochrome oxidase is decreased preferentially under conditions of iron deficiency and addition of iron corrects this picture. Exogenous hemin addition which prevents iron-mediated induction of delta-aminolevulinate dehydratase also inhibits the increase in the activity of cytochrome oxidase and the enhanced precursor labeling of the mitochondrial subunits of cytochrome oxidase. Protein synthesis on mitoribosomes measured in vivo and in vitro is decreased under conditions of heme deficiency. Hemin addition in vitro to mitochondrial lysates prepared from heme-deficient mycelia restores a near normal rate of protein synthesis. It is concluded that heme is required for the optimal rate of translation on mitoribosomes. PMID- 6254960 TI - On the role of the covalent carbohydrate in the action of ricin. AB - the covalent carbohydrate in the toxic lectin ricin has been modified by periodate treatment, and analysis of the products of this reaction indicates that only mannose residues are oxidized. HeLa cell toxicity, cell-surface binding, inhibition of cell-free protein synthesis, and other properties have been investigated as functions of the number of mannose residues modified. The data indicate an important role for mannose in ricin conformation and in the endocytotic process; however, mannose appears not to be essential for binding the toxin to cells. PMID- 6254962 TI - Disparities in the interaction of rat and human lipoproteins with cultured rat fibroblasts and smooth muscle cells. Requirements for homology for receptor binding activity. AB - This study characterizes the interactions of various rat and human lipoproteins with the lipoprotein cell surface receptors of rat and human cells. Iodinated rat very low density lipoproteins (VLDL), rat chylomicron remnants, rat low density lipoproteins (LDL), and rat high density lipoproteins containing predominantly apoprotein E (HDL1) bound to high affinity cell surface receptors of cultured rat fibroblasts and smooth muscle cells. Rat VLDL and chylomicron remnants were most avidly bound; the B-containing LDL and the E-containing HDL1 displayed lesser but similar binding. Rat HDL (d = 1.125 to 1.21) exhibited weak receptor binding; however, after recentrifugation to remove apoprotein E, they were devoid of binding activity. Competitive binding studies at 4 degrees C confirmed these results for normal lipoproteins and indicated that VLDL (B-VLDL), LDL, and HDLc (cholesterol-rich HDL1) isolated from hypercholesterolemic rats had increased affinity for the rat receptors compared with their normal counterparts, the most pronounced change being in the LDL. The cell surface receptor pathway in rat fibroblasts and smooth muscle cells resembled the system described for human fibroblasts as follows: 1) lipoproteins containing either the B or E apoproteins interacted with the receptors; 2) receptor binding activity was abolished by acetoacetylation or reductive methylation of a limited number of lysine residues of the lipoproteins; 3) receptor binding initiated the process of internalization and degradation of the apo-B- and apo-E-containing lipoproteins; 4) the lipoprotein cholesterol was re-esterified as determined by [14C]oleate incorporation into the cellular cholesteryl esters; and 5) receptor-mediated uptake (receptor number) was lipoprotein cholesterol. An important difference between rat and human fibroblasts was the inability of human LDL to interact with the cell surface receptors of rat fibroblasts. Rat lipoproteins did, however, react with human fibroblasts. Furthermore, the rat VLDL were the most avidly bound of the rat lipoproteins to rat fibroblasts. When the direct binding of 125I VLDL was subjected to Scatchard analysis, the very high affinity of rat VLDL was apparent (Kd = 1 X 10(-11) M). Moreover, compared with data for rat LDL, the data suggested each VLDL particle bound to four to nine lipoprotein receptors. This multiple receptor binding could explain the enhanced binding affinity of the rat VLDL. The Scatchard plot of rat 125I-VLDL revealed a biphasic binding curve in rat and human fibroblast cells and in rat smooth muscle cells, suggesting two populations of rat VLDL. These results indicate that rat cells have a receptor pathway similar to, but not identical with, the LDL pathway of human cells. Since human LDL bind poorly to rat cell receptors on cultured rat fibroblasts and smooth muscle cells, metabolic studies using human lipoproteins in rats must be interpreted cautiously. PMID- 6254963 TI - The novel "g' = 1.74" EPR spectrum of pink and purple uteroferrin. AB - Low temperature (T less than or equal to 20 K) EPR measurements have revealed the presence of a heretofore undetected signal in uteroferrin, a purple protein bearing a single iron atom per molecule. All three of its principal g values (1.923, 1.738, and 1.583) lie well below the free electron value of 2.0023. Magnetic susceptibility data from 2-77 K confirm that the novel EPR spectrum arises from a paramagnetic center with a single unpaired electron spin. Quantitative correlation of the EPR, susceptibility, and optical data point to chromophoric iron as the source of the rhombic EPR spectrum. Furthermore, close agreement between the concentration of iron and the integrated intensity of the rhombic EPR signal show that the iron in the paramagnetic center is mononuclear. Reduction of the protein to its pink form leaves the rhombic signal essentially unaltered. The previously reported g' = 4.3 EPR signal accounts for only a small fraction of the total iron in the protein and undoubtedly arises from adventitious iron. Collectively, these results strongly suggest that uteroferrin represents a new class of low spin iron proteins. PMID- 6254964 TI - Renal parathyroid hormone-dependent adenylate cyclase in vitamin D-deficient rats. Inhibition by hydroxylated vitamin D3 metabolites. AB - The adenylate cyclase activation by bovine synthetic parathyroid hormone (bPTH) (1-34) was studied in vitro in kidney plasma membranes from D-deficient (D-Mb) or normal (D+Mb) rats. In D-Mb, the apparent affinity of parathyroid hormone (PTH) for membranes (170 +/- 30 nM) was significantly higher than that measured in D+Mb (55 +/- 5 nM). The maximum velocity of the PTH-stimulated adenylate cyclase was significantly higher in D+Mb than in D-Mb (163.0 +/- 13.7 and 93.4 +/ 6.7 pmol of cAMP/mg of protein/min, respectively). The action of vitamin D metabolites on the adenylate cyclase stimulation by PTH was then studied in vitro in D-Mb and D+Mb. In D-Mb, 25-hydroxyvitamin D3, 24,25-, and 1, 25 dihydroxyvitamin D3 significantly inhibited cAMP production in the presence of 0.87 microM of bPTH. Vitamin D3 had no effect. Maximal inhibition (86%) was observed for 1,25-dihydroxyvitamin D3. 1,25-Dihydroxyvitamin D3 decreased the maximum velocity of PTH-stimulated adenylate cyclase but did not modify the bPTH apparent affinity for D-Mb. The vitamin D3 metabolites tested did not modify the cyclase stimulation by isoproterenol, sodium fluoride, or 5' guanylylimidodiphosphate. The presence of 1,25-dihydroxyvitamin D3 or 25 hydroxyvitamin D3 did not increase the (Na-K)-ATPase or the phosphodiesterase activities. In the presence of 1,25-dihydroxyvitamin D3 and bPTH, the apparent affinity of ATP for the catalytic moiety was not modified. The maximum velocity was decreased. These results suggest an in vitro interaction between hydroxylated vitamin D metabolites and kidney membranes PTH receptor. PMID- 6254966 TI - Phosphopeptide substrates of a phosphoprotein phosphatase from rat liver. AB - The substrate specificity of a preparation of phosphoprotein phosphatase (Mr = 32 000) from rat liver was investigated. Phosphopeptides based on the structure Leu Arg-Arg-Ala-Ser(P)-Val-Ala-Glx-Leu and Ala-Arg-Thr-Lys-Arg-Ser-Gly-Ser(P)-Val-Tyr Glu-Pro-Leu-Lys were used. These phosphopeptides correspond to the phosphorylation sites of rat liver pyruvate kinase (type L) and the beta subunit of rabbit muscle phosphorylase b kinase, respectively. A decrease in the apparent Km values and a concomitant increase in Vmax values was observed when the number of amino acyl residues after the phosphoseryl residue in the respective phosphopeptides were increased from 2 to 4, 5, or 6. Most of the phosphopeptides investigated generally showed apparent Km values higher than the values obtained with phosphopyruvate kinase. Ala-Ser(P)-Val-Ala and Gly-Ser(P)-Val-Tyr appeared to be the shortest phosphopeptides that could be dephosphorylated rapidly. These findings support the hypothesis that a small part of the phosphoprotein may be sufficient to fulfill the minimal requirements for its dephosphorylation. PMID- 6254965 TI - Subunit interactions inhibit the binding of beta nerve growth factor to receptors on embryonic chick sensory neurons. AB - The binding of the beta nerve growth factor subunit in the 7 S nerve growth factor complex to the two nerve growth factor receptors on chick embryo dorsal root ganglion cells was investigated. Under conditions where the 7 S nerve growth factor complex is maximally stable (in the presence of excess alpha and gamma subunits and of 20 to 30 microM zinc ion), no binding to either receptor was detectable. The time course of the decrease in the binding of beta nerve growth factor to the receptors upon addition of alpha and gamma subunits and zinc ion paralleled the formation of the 7 S complex. Addition of alpha and gamma subunits and zinc ion to the bisdes-arginine118-nerve growth factor, which does not re form the 7 S complex, failed to inhibit the binding of the derivative to either receptor. While the alpha subunit alone had no effect on beta nerve growth factor binding, the gamma subunit decreased its binding in proportion to the amount of complex formed between these two subunits, suggesting that the beta . gamma complex, like the 7 S complex, does not bind to nerve growth factor receptors. PMID- 6254967 TI - Location of heme a on subunits I and II and copper on subunit II of cytochrome c oxidase. AB - A systemic study has been made of copper and heme a binding to subunits of beef heart cytochrome c oxidase. Copper and heme a were readily mobilized by ionic detergents, high ionic strengths, temperatures above 0 degrees C, thiol compounds, and gel-bound peroxides and free radicals when the subunits of the oxidase were dissociated from one another during polyacrylamide gel electrophoresis. Most subunits showed some affinity for heme a and copper under these conditions. However, in the presence of specific mixtures of ionic and nonionic detergents (e.g. 0.1% sodium dodecyl sulfate, 0.025% Triton X-100) at temperatures below 0 degrees C and in buffers of low ionic strength using 10 to 12% polyacrylamide gels preelectrophoresed for 3 days with thioglycolate, about 90% of the Cu was found on subunit II (Mr = 24,100), and heme a was found in equal amounts of subunits I (Mr = 35,800) and II. The oxidized-reduced and reduced-CO absorption spectra of these subunits resembled those of cytochrome c oxidase. It appears probable that in the native enzyme, subunit I contains heme a and subunit II contains copper and heme a. A relationship of mammalian cytochrome c oxidase to the two-subunit microbial cytochrome oxidase systems appears to exist. PMID- 6254968 TI - Temperature-dependent cytosol-to-nucleus translocation of the Ah receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin in continuous cell culture lines. PMID- 6254969 TI - Periodate inactivation of ovotransferrin and human serum transferrin. AB - Azari and Phillips (Azari, P., and Phillips, J. L. 1970 Arch. Biochem. Biophys. 138, 32-38) reported that periodate treatment of iron-free ovotransferrin causes a rapid loss of iron-binding activity and an oxidation of 3 to 5 tyrosines and 1 tryptophan. Rapid inactivation and loss of tyrosine in ovotransferrin has been confirmed, and the work extended to human serum transferrin and effects of denaturing concentrations of urea. Extensive (> 80%) inactivations of both ovotransferrin and human serum transferrin were observed when approximately 4 tyrosines were destroyed. Amino acid analysis and 360-MHz 1H NMR spectra confirmed that tyrosines are the only residues rapidly oxidized; the correlation of tyrosine loss with the loss of iron-binding activity suggests strongly that the tyrosines involved are those that function as ligands to metal ions bound to the protein. NMR spectra also showed that periodate oxidation causes local changes of structure in ovotransferrin (presumably at the metal-binding sites) but does not grossly alter the conformation. The addition of 5 to 8 M urea greatly retarded the inactivation and losses of tyrosine. PMID- 6254970 TI - Partial purification and characterization of the low density lipoprotein receptor from bovine adrenal cortex. AB - The low density lipoprotein (LDL) receptor has been solubilized from bovine adrenocortical membranes with octyl-beta-D-glucoside and purified 350-fold in the presence of the detergent. The activity of the solubilized receptor was assayed by precipitating the receptor with acetone in the presence of egg phosphatidylcholine liposomes. the receptor-phosphatidylcholine liposomes bound 125I-LDL with the same affinity and specificity as did the native LDL receptor of intact membranes. The complex of receptor and octylglucoside had a Stokes radius of 53.5 A as determined by agarose gel filtration. The sedimentation coefficient, s20,w, of the receptor . octylglucoside complex was 7.3 as determined by metrizamide density gradient centrifugation. An identical value for the sedimentation coefficient was obtained when deuterium oxide was substituted for water in the metrizamide gradient. These data were used to derive an estimate of 163,000 for the molecular weight of the LDL receptor . octylglucoside complex (range of molecular weight, 152,000 to 170,000). The receptor is an acidic protein as determined by its behavior on ion exchange chromatography. In the most highly purified LDL receptor preparation, which had been subjected to the sequential steps of solubilization, DEAE-cellulose chromatography, agarose gel filtration, and phosphatidylcholine/acetone precipitation, the receptor was estimated to constitute about 5% of the total protein. Thus, complete purification of the LDL receptor from bovine adrenocortical membranes will require an additional 20-fold purification, or a total purification of about 7,000-fold. PMID- 6254971 TI - Proteolytic removal of the COOH terminus of the T4 gene 32 helix-destabilizing protein alters the T4 in vitro replication complex. AB - The proteolytic removal of about 60 amino acids from the COOH terminus of the bacteriophage T4 helix-destabilizing protein (gene 32 protein) produces 32*I, a 27,000-dalton fragment which still binds tightly and cooperatively to single stranded DNA. The substitution of 32*I protein for intact 32 protein in the seven protein T4 replication complex results in dramatic changes in some of the reactions catalyzed by this in vitro DNA replication system, while leaving others largely unperturbed. 1. Like intact 32 protein, the 32*I protein promotes DNA synthesis by the DNA polymerase when the T4 polymerase accessory proteins (gene 44/62 and 45 proteins) are also present. The host helix-destabilizing protein (Escherichia coli ssb protein) cannot replace the 32I protein for this synthesis. 2. Unlike intact 32 protein, 32*I protein strongly inhibits DNA synthesis catalyzed by the T4 DNA polymerase alone on a primed single-stranded DNA template. 3. Unlike intact 32 protein, the 32*I protein strongly inhibits RNA primer synthesis catalyzed by the T4 gene 41 and 61 proteins and also reduces the efficiency of RNA primer utilization. As a result, de novo DNA chain starts are blocked completely in the complete T4 replication system, and no lagging strand DNA synthesis occurs. 4. The 32*I protein does not bind to either the T4 DNA polymerase or to the T4 gene 61 protein in the absence of DNA; these associations (detected with intact 32 protein) would therefore appear to be essential for the normal control of 32 protein activity, and to account at least in part for observations 2 and 3, above. We propose that the COOH-terminal domain of intact 32 protein functions to guide its interactions with the T4 DNA polymerase and the T4 gene 61 RNA-priming protein. When this domain is removed, as in 32*I protein, the helix destabilization induced by the protein is controlled inadequately, so that polymerizing enzymes tend to be displaced from the growing 3'-OH end of a polynucleotide chain and are thereby inhibited. Eukaryotic helix-destabilizing proteins may also have similar functional domains essential for the control of their activities. PMID- 6254972 TI - DNA site recognition and reduced specificity of the Eco RI endonuclease. AB - It has been shown previously (Polisky, B., Green, P., Garfin, D. E., McCarthy, B. J., Goodman, H. M., and Boyer, H. W. (1975) Proc. Natl. Acad. Sci. U. S. A. 72, 3310-3314; Hsu, M., and Berg, P. (1978) Biochemistry 17, 131-138) that the cleavage sequence specificity of Eco RI endonuclease can be "relaxed" by various means. In this paper this phenomenon is explored in detail, in order to obtain further insight into the nature and selectivity of sequence recognition patterns between proteins and double-stranded nucleic acids. Using conditions of low ionic strength and alkaline pH, we have mapped the positions of potentially cleavable sites in the (completely sequenced) replicative form of the bacteriophage phi X174 genome, and have deduced their sequence. The time course of digestion of phi X174 DNA suggests that double-stranded sequences reading GGATTT, AAATTT, GAATTT, and GAATTA (only "top" strands, written 5' leads to 3', are shown) are cleaved readily under these conditions, while sequences reading CAATTN (N = A, T, G) resist attack. Cleavages at (at least) the more labile sites result in cohesive ends that are religatable. End group analysis of cleaved phi X174 DNA fragments indicates the presence of a 5'-terminal adenine residue on most of the fragments; some fragments may carry a 5'-terminal guanine residue, consistent with the cleavage site sequences suggested above. Addition of Mn2+ to cleavage reactions carried out at moderate salt concentrations and near-neutral pH induces the same pattern of cleavage seen at low ionic strength and alkaline pH. These results are combined with those from other studies, and are interpreted in terms of a model for the site-specific interaction of the Eco RI endonuclease with its substrate, considering both the effects of changes in DNA sequence and of environmental alterations. The resulting model is compared with data developed on similar grounds for Eco RI methylase (see Woodbury, C. P., Downey, R. L., and von Hippel, P. H. (1980) J. Biol. Chem. 255, 11526-11533), and attempts are made to define both common and differing molecular facets of the DNA recognition specificity of these companion (but genetically distinct) enzymes. PMID- 6254973 TI - Studies on the structure of mouse helix-destabilizing protein-1. DNA binding and controlled proteolysis with trypsin. AB - A mouse helix-destabilizing protein (HD protein-1) has been purified and characterized, and controlled tryptic digestion has been used to generate two large fragments of this protein and to study structural changes accompanying DNA binding. HD protein-1, a DNA-binding protein that has higher affinity for single stranded DNA (ssDNA)-cellulose than for double-stranded DNA (dsDNA)-cellulose and is resistant to a dextran sulfate elution from ssDNA-cellulose, was purified from mouse myeloma by the method described by Herrick and Alberts (Herrick, G., and Alberts, B. M. (1976) J. Biol. Chem. 251, 2124-2132). HD protein-1 was heterogeneous with regard to apparent molecular weight (range of Mr = 24,000 to 33,000), but individual Mr species shared extensive primary structure homology as revealed by tryptic peptide mapping. The predominant species of this protein, Mr = 27,000, was resolved from other species and obtained in nearly homogeneous form by preparative isoelectric focusing. Mouse HD protein-1 was capable of lowering the Tm of poly[d(A-T)] by 25 degrees C, indicating that it is a helix destabilizing protein. Sedimentation boundary analysis revealed that binding to ssDNA was noncooperative and that the binding site covered about 6 nucleotide residues. There was a 35% increase in the intrinsic tryptophan fluorescence of the protein in the presence of ssDNA, suggesting that structural change accompanies binding. Subcellular localization studies indicated that 75% of mouse HD protein-1 is nuclear, but not chromatin-associated, and primary structure analysis indicated that HD protein-1 is distinct from high mobility group proteins 1 and 2, histones, and P8 protein. Tryptic hydrolysis of HD protein-1 produced discrete, large fragments whose apparent molecular weights ranged from 19,000 to 24,000, and whose relative abundance was changed by the presence of ssDNA during the digestion. Thus, a Mr = 22,000 fragment (22 HDP*) predominated in the absence of ssDNA, and a Mr = 19,000, fragment (19 HDP*) predominated in the presence of ssDNA. Poly(dT) and denatured calf thymus DNA were more effective than were other polynucleotides tested in promoting accumulation of 19 HDP*; (dT)8 was as effective as were longer molecules of (dT)n, but (dT)4 and (dT)6 were much less effective, indicating that the binding site involved in 19 HDP* accumulation covered between 6 and 8 residues of (dT)n. Both 19 HDP* and 22 HDP* have the same COOH-terminal end and the same affinity for ssDNA-cellulose as does the native HD protein-1, indicating that a Mr = 8,000 sequence at the NH2 terminal end of HD protein-1 is not required for binding to ssDNA. Even though 22 HDP* retained the ability to bind to ssDNA, it could not be converted to 19 HDP* by further trypsin digestion. PMID- 6254974 TI - Purification and characterization of a GTP-pyrophosphate exchange activity from vaccinia virions. Association of the GTP-pyrophosphate exchange activity with vaccinia mRNA guanylyltransferase . RNA (guanine-7-)methyltransferase complex (capping enzyme). AB - A core-associated enzyme, which catalyzes a nucleotide-pyrophosphate exchange with GTP, has been purified from vaccinia virions. The enzyme requires MgCl2 for activity, has an alkaline pH optimum, and specifically utilizes GTP as the exchanging nucleotide. The enzyme does not catalyze exchange of GMP with GTP. The GTP-PPi exchange enzyme co-purifies with vaccinia capping enzyme (RNA guanylyltransferase and RNA (guanine-7-)methyltransferase) through successive chromatography steps on DEAE-cellulose, DNA-cellulose, and phosphocellulose. GTP PPi exchange and capping activities remain physically associated during sedimentation in a glycerol gradient. Under high salt conditions (1 M NaCl), GTP PPi exchange, capping, and methylating activities co-sediment with an RNA triphosphatase activity and a nucleoside triphosphate phosphohydrolase activity as a 6.5 S multifunctional enzyme complex which contains two major polypeptides of 96,000 and 26,000 molecular weight. The characteristics of the various enzymatic reactions catalyzed by this complex are described. The GTP-PPi exchange reaction of vaccinia guanylyltransferase affords a simple, sensitive assay for capping enzyme function. The relevance of the GTP-PPi exchange reaction to the mechanism of transguanylylation is considered. PMID- 6254975 TI - The transcription map of human mitochondrial DNA implicates transfer RNA excision as a major processing event. PMID- 6254976 TI - Cyclic GMP-specific, high affinity, noncatalytic binding sites on light-activated phosphodiesterase. AB - Two classes of high affinity, cGMP-specific binding sites have been found in association with a peripheral membrane protein in rod outer segments. [3H]cGMP and a photoaffinity label, 8-N3-[32P]cIMP, have been used to study these cGMP binding sites. The cGMP binding sites co-migrated with rod outer segment phosphodiesterase (EC 3.1.4.17) upon Bio-Gel A-0.5m column chromatography, sucrose density gradient centrifugation, and isoelectric focusing (pI 5.35). Upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the 8-N3-[32P]cIMP labeled protein also migrated in a position identical with that of purified phosphodiesterase. Scatchard analysis, using purified phosphodiesterase, revealed the presence of two classes of cGMP binding sites with apparent KD values of 0.16 and 0.83 microM. A number of observations indicated that these high affinity, cGMP-specific binding sites are distinct from the phosphodiesterase catalytic site. cAMP, which is a substrate for phosphodiesterase, did not bind to the high affinity cGMP specific sites. Limited tryptic proteolysis of phosphodiesterase resulted in a striking activation of the catalytic activity and a 96% loss of cGMP binding. 1-Methyl-3-isobutylxanthine inhibited phosphodiesterase activity and enhanced the specific binding of cGMP. Mg2+ was necessary for phosphodiesterase activity, but not for high affinity cGMP binding. Finally, phosphodiesterase activity and the cGMP-specific high affinity sites showed different stabilities on storage in phosphate buffer. These specific high affinity cGMP binding sites may be involved in the regulation of phosphodiesterase activity. PMID- 6254977 TI - Octopus calmodulin. Structural comparison with bovine brain calmodulin. AB - A protein previously isolated from octopus optic lobe is shown to have the biochemical characteristics of a calmodulin-like protein. The amino acid composition of the octopus calmodulin is similar to that of another sea invertebrate calmodulin, from Renilla reniformis, in that both contain a single residue of tyrosine which distinguishes them from the vertebrate calmodulins which contain two tyrosines. The 1H NMR spectra of the octopus calmodulin and bovine brain calmodulin are compared in their apo- and calcium-saturated conformations. A comparison of these spectra indicates that the single tyrosine of the octopus calmodulin is in a structurally homologous position to tyrosine 138 of bovine brain calmodulin. 1H NMR and UV difference spectroscopy also demonstrate that the solution conformations of the apo- and calcium-saturated forms of octopus calmodulin are very similar to those of bovine brain calmodulin. It is concluded that both proteins undergo similar calcium-induced changes in tertiary structure, which result in near identical solution conformations. PMID- 6254978 TI - The dnaZ protein, the gamma subunit of DNA polymerase III holoenzyme of Escherichia coli. AB - The dnaZ protein has been purified to near-homogeneity using an in vitro complementation assay that measures the restoration of activity in a crude enzyme fraction from the dnaZ mutant deficient in the replication of phi X174 DNA. Over 70-fold overproduction of the protein was obtained with a bacteriophage lambda lysogen carrying the dnaZ gene. The purified protein, under reducing and denaturing conditions, has a molecular weight of 52,000 and appears to be a dimer in its native form. The dnaZ protein is judged to be th 52,000-dalton gamma subunit of DNA polymerase III holoenzyme (McHenry, C., and Kornberg, A. (1977) J. Biol. Chem. 252, 6478-6484) for the following reasons: (i) highly purified DNA polymerase III holoenzyme contains a 52,000-dalton polypeptide and has dnaZ complementing activity; (ii) the 52,000-dalton polypeptide is associated tightly with the DNA polymerase III holoenzyme and can be separated from the DNA polymerase III core only with severe measures; (iii) no other purified replication protein, among 14 tested, contains dnaZ protein activity; and (iv) the abundance of dnaZ protein, estimated at about 10 dimer molecules per Escherichia coli cell, is similar to that of the DNA polymerase III core. Among several circular templates tested in vitro (i.e. single stranded phi X174, G4 and M13 DNAs, and duplex phi X174 DNA), all rely on dnaZ protein for elongation by DNA polymerase III holoenzyme. The protein acts catalytically at a stoichiometry of one dimer per template. PMID- 6254979 TI - Purification and properties of alpha-N-acetylgalactosaminidase from Clostridium perfringens. AB - Exo-alpha-N-acetylgalactosaminidase has been purified 8000-fold from Clostridium perfringens by gel filtration, ion exchange chromatography, isoelectric precipitation, and negative adsorption on human O type erythrocytes. The resulting enzyme is active at physiological pH and temperature. Phenyl glycosides, oligosaccharides, mucins, glycolipids, and cell membranes are substrates for this enzyme. The result of enzyme action on blood type A erythrocytes is the loss of A activity and the simultaneous appearance of H activity, characteristic of the O blood group type. Polyacrylamide gel electrophoresis in sodium dodecyl sulfate demonstrates electrophoresis in sodium dodecyl sulfate demonstrates that the blood group A-destroying activity is distinct from the other glycosidase activities found in C. perfringens. PMID- 6254980 TI - Further characterization of human fibroblast apurinic/apyrimidinic DNA endonucleases. The definition of two mechanistic classes of enzyme. PMID- 6254981 TI - ATP x Mg-dependent protein phosphatase from rabbit skeletal muscle. I. Purification of the enzyme and its regulation by the interaction with an activating protein factor. AB - An ATP x Mg-dependent protein phosphatase (FC) was purified to near homogeneity from rabbit muscle. The enzyme was completely devoid of any spontaneous activity but could be activated by a protein activator (FA) in the presence of ATP and Mg ions. The inactive phosphatase migrated as a single protein band on sodium dodecyl sulfate-gel electrophoresis, and in discontinuous gel electrophoresis, where the potential phosphatase activity was located in the main protein band. The molecular weight determined by sodium dodecyl sulfate electrophoresis or by sucrose density centrifugation was found to be 70,000. FC migrated on gel filtration as a 140,000 molecular weight species. The activation by FA was not paralleled by an incorporation of [32P]-phosphate into the ATP x Mg-dependent phosphatase, and from the kinetics of activation a protein-protein interaction with ATP x Mg as a necessary factor, can be inferred as the mechanism of activation. After activation by FA and ATP X Mg, the purified enzyme had a specific activity of 10,000 units/mg of protein, and a Km for rabbit muscle phosphorylase a of approximately 1.0 mg/ml. The activated enzyme did not release [32P]phosphate from 32[-labeled rabbit muscle synthase b, prepared from glucagon treated dogs. It did, however, remove all the 32P label from phosphorylase b kinase, autophosphorylated to the level of 2.0 mol/mol of 1.3 X 10(6) molecular weight. PMID- 6254982 TI - ATP x Mg-dependent protein phosphatase from rabbit skeletal muscle. II. Purification of the activating factor and its characterization as a bifunctional protein also displaying synthase kinase activity. AB - A protein (FA) has been isolated from rabbit muscle which has two functions: one is the activation of the ATP x Mg-dependent phosphatase (see previous paper) (1) and the second is the phosphorylation and concomitant inactivation of glycogen synthase, independent from cyclic AMP or Ca ions. The two activities co-purify throughout the purification scheme, and reside in the single protein band that the purified preparation shows in discontinuous acrylamide gel electrophoresis. Heat inactivation experiments with the purified protein showed a parallel decrease of both activities with time. GTP could efficiently replace the ATP in both reactions. Sodium dodecyl sulfate-gel electrophoresis also shows a single protein-stained band corresponding to a Mr = approximately 50,000 and sucrose density gradient centrifugation gave a value of 45,000. The enzyme incorporates only 1 mol of phosphate/mol of synthase monomer (85,000 daltons) and brings the activity ratio (+/- glucose-6-P) down to less than 0.05. Kinetic studies suggest that FA exerts its two activities in quite different ways: the activation of the ATP x Mg-dependent phosphatase is bought about by a protein-protein interaction (FA x FC complex formation) with ATP x Mg as a necessary cofactor, whereas for the inactivation of synthase, FA is a cyclic AMP- and Ca-independent kinase. PMID- 6254983 TI - Leukotriene A. Isolation from human polymorphonuclear leukocytes. AB - Leukotriene A, an unstable intermediate in the conversion of arachidonic acid to stable leukotrienes, was isolated from human polymorphonuclear leukocytes. The allylic epoxide intermediate is rapidly hydrolyzed under acidic conditions. A method was therefore developed for esterification and extraction of the intermediate as the methyl ester from an alkaline aqueous phase, into an aprotic solvent. This was achieved by addition of methanol and an excess of diazomethane in ether to the incubatio mixture, followed by addition of water, and phase separation. The identity of the isolated compound with the previously synthesized methyl ester of 5 (S)-trans-5,6-oxido-7,9-trans-11,14-cis-eicostatetraenoic acid (leukotriene A), was established by comparing chromatographic and chemical properties of the isolated compound and synthetic leukotriene A. PMID- 6254984 TI - Acid-alkaline transition and thermal spin equilibrium of the heme in ferric L tryptophan 2,3-dioxygenases. PMID- 6254985 TI - Assembly of the mitochondrial membrane system. Physical map of the Oxi3 locus of yeast mitochondrial DNA. AB - The oxi3 locus of yeast mitochondrial DNA is currently thought to code for Subunit 1 of cytochrome oxidase (Tzagoloff, A., Macino, G., and Sebald, W. (1979) Annu. Rev. Biochem. 48, 419-441). The respiratory competent strain of Saccharomyces cerevisiae D273-10B/A48 was used to obtain cytoplasmic "petite" clones enriched for genetic markers in the oci3 locus. The most complex clone studied (DS6) was ascertained to have a mitochondrial genome with a tandemly repeated segment of mtDNA 16.5 kilobases in length. The oxi3 locus was dissected by mutagenesis of DS6 with ethidium bromide and selection of new clones having less complex genotypes. Six derivative clones with genome sizes ranging from 2.3 to 6.1 kilobases have been extensively analyzed. Most of the restriction sites present in the segments of mtDNA retained by the clones have been mapped, thereby providing a detailed restriction map of the oxi3 gene. Based on the physical locations of the most distal oxi3 mutations, the gene spans approximately 10,000 nucleotides and occupies the region of wild type mtDNA from 44 to 58 map units. PMID- 6254986 TI - Assembly of the mitochondrial membrane system. Structure and nucleotide sequence of the gene coding for subunit 1 of yeast cytochrme oxidase. AB - the oxi3 locus of yeast mitochondrial DNA has been sequenced in Saccharomyces cerevisiae D273-10B. The sequence was obtained from the mitochondrial genomes of a series of cytoplasmic "petite" mutants selected for the retention of genetic markers in the oxi3 locus. The oxi3 locus has been ascertained to code for Subunit 1 of cytochrome oxidase. The Subunit 1 gene is 9,979 nucleotides long, consisting of seven to eight exons that account for only 16% of the gene sequence. The coding sequences have been identified on the basis of protein sequence homology with Subunit 1 of human cytochrome oxidase. The yeast Subunit 1 is 510 amino acid residues long and has a molecular weight of 56,000. In addition to the exon sequences, the Subunit I gene contains six to seven introns. The first four introns have long reading frames that are continuous with the exon coding sequences. These reading frames are potentially capable of coding for basic proteins with molecular weights ranging from 30,000 to 80,000. The first two introns of the gene have a sequence homology of 50%, while the reading frame of the fourth intron is 70% homologous with an intron of the apocytochrome b gene. At least five stable transcripts have been found by Northern blot hybridizations with single-stranded DNA probes containing either exon or intron sequences. A 1.9-kolobase transcript hybridizes only with probes from the exon regions of the gene. This RNA species has been tentatively identified as the fully processed messenger of Subunit 1. Other transcripts are detected with intron probes. Three transcripts with sizes of 2.5, 2.4, and 0.85 kilobases appear to be stable excision products from the first, second, and fifth introns. PMID- 6254987 TI - Mannose 6-phosphate receptor-mediated uptake of modified low density lipoprotein results in down regulation of hydroxymethylglutaryl-CoA reductase in normal and familial hypercholesterolemic fibroblasts. AB - Monophosphotetramannosyl-1-deoxymannitol-1-yl-low density lipoprotein (Man-6-P LDL) was prepared by covalent attachment of the pentasaccharide omega-(6-phospho tetra(alpha 1-3)mannosyl(alpha 1-2)mannose to amino groups on low density lipoprotein. Normal human fibroblasts were shown to specifically bind, internalize, and degrade 125I-labeled Man-6-P-LDL. Specificity for the mannose 6 phosphate (Man-6-P) receptor was demonstrated by competitive displacement with cold Man-6-P-LDL, Man-6-P, or mannose. No displacement was seen with cold LDL. Kd is estimated to be less than or equal to 2 X 10(-9) M. Degradation of 125I labeled Man-6-P-LDL in familial hypercholesterolemic fibroblasts showed the same time course and specificity as observed in normal fibroblasts. Man-y-P-LDL was also able to deliver cholesterol to the cytosol where down regulation of the enzyme 3-hydroxy-3-methylglutaryl CoA reductase was observed in both normal and familial hypercholesterolemic fibroblasts. Down regulation could be blocked by Man-6-P in both cell lines. The possible uses of agents such as Man-6-P-LDL as research probes and therapeutic tools directed to specific cell types are discussed. PMID- 6254988 TI - The purified product of the transforming gene of avian sarcoma virus phosphorylates tyrosine. AB - The product of the avian sarcoma virus transforming gene (src) is a phosphoprotein of 60,000 daltons (pp60src) which is responsible for the oncogenic potential of the virus. Recent findings indicate that this protein possesses an affiliated protein kinase activity. We have determined by hydrodynamic measurements and gel filtration that this kinase activity tracks with a highly asymmetric molecule of 60,000 daltons, strengthening the idea that pp60src alone (as opposed to a complex) possesses the enzymatic activity. To more fully characterize the properties of this kinase activity, we undertook its purification by two independent methods. In each case, a protein related to pp60src was extensively purified from contaminating cellular proteins. The yields from one of the procedures were sufficient to induce high titer monospecific antibodies against pp60src in mice. We have shown that purified pp60src is able to phosphorylate several protein substrates other than IgG. The conclusion that pp60src possesses the responsible enzymatic activity was strengthened by demonstrating that a temperature-sensitive conditional mutation in src affected the thermal stability of the purified protein. It has recently been shown that the protein kinase activity affiliated with pp60src phosphorylates tyrosine residues on IgG. We have examined the target specificity of the purified protein on several substrates other than IgG, and show that in every case, the phosphorylation occurs exclusively at a tyrosine residue; it therefore appears that tyrosine phosphorylatin is not an artifact of phosphorylation in th immunoprecipitate, but instead represents the general substrate specificity of pp60src. PMID- 6254989 TI - Specific cleavage of human type III collagen by human polymorphonuclear leukocyte elastase. AB - Purified polymorphonuclear leukocyte elastase degraded native human liver type III collagen at 27 degrees C by making a cleavage through the triple helix. The enzyme had no effect on human type I collagen. The reaction was inhibited by phenylmethanesulfonyl fluoride (PhCH2SO2F) but not by EDTA. The collagen reaction products were identical with those generated by human rheumatoid synovial collagenase when analyzed by polyacrylamide gel electrophoresis and gel filtration. NH2-trminal sequence analysis indicated that the enzyme cleaved at an isoleucyl-threonyl bond located 4 residues on the carboxyl side of the established cleavage site for animal collagenases. Therefore, it is likely that in pathologic states, type III collagen can be selectively depleted from the matrix by this enzyme. PMID- 6254990 TI - Ligand interactions of diphtheria toxin. I. Binding and hydrolysis of NAD. AB - Prior studies showed that diphtheria toxin could be separated into ATP-binding and nonbinding fractions (Fractions II and I, respectively) by affinity chromatography on ATP-Sepharose (Lory, S., and Collier, R. J. (1980) Proc. Natl. Acad. Sci. U. S. A. 77, 267-271). Here we show that the two fractions also differ in their interactions with NAD. Fraction II bound a single molecule of NAD (Kd about 9 microM) as assayed by flow dialysis or fluorescence quenching and catalyzed both NAD-glycohydrolase and auto-ADP-ribosylation reactions. Fraction I was deficient in NAD-binding and NAD-related reactions. The ratio of the two fractions vried widely among toxin preparations and was independent of the proportion of toxin in the nicked state. Properties of th NAD site on Fraction II were similar to, but not identical with, those of the corresponding site on free Fragment A. PMID- 6254991 TI - Comparison of the cleavage of pyrimidine dimers by the bacteriophage T4 and Micrococcus luteus UV-specific endonucleases. AB - A comparison was made of the activity of the UV-specific endonucleases of bacteriophage T4 (T4 endonuclease V) and of Micrococcus luteus on ultravilet light-irradiated DNA substrates of defined sequence. The two enzymes cleave DNA at the site of pyrimidine dimers with the same frequency. The products of the cleavage reaction are the same, suggesting that the scission of DNA by T4 endonuclease V occurs via the combined actin of a pyrimidine dimer specific DNA glycosylase and an apyrimidinic-apurinic (AP) endonuclease as was recently shown for the M. luteus enzyme. The pyrimidine dimer DNA-glycosylase activity of both enzymes is more active on double-stranded DNA than it is on single-stranded DNA. PMID- 6254992 TI - Isolation and characterization of the yeast 3-phosphoglycerokinase gene (PGK) by an immunological screening technique. AB - An immunological screening technique has been used for the detection of a specific antigen-producing clone in a bank of bacterial colonies containing hybrid plasmids. This technique involves covalent attachment of antiserum to cyanogen bromide-activated paper discs, contact of this paper with lysed colonies on agar plates, and finally detection of the bound antigen with 125I-labeled antibody. Using this method, we have identified an Escherichia coli colony, containing a yeast DNA insert in plasmid ColE1, that produces antigen which combines with antibody directed against purified yeast 3-phosphoglycerate kinase. The hybrid plasmid (pYe57E2) obtained by this procedure has been shown by both biochemical and genetic methods to contain the structural gene PGK for yeast 3 phosphoglycerate kinase. The location of the PGK structural gene on pYe56E2 was determined by immunological screening of E. coli colonies bearing plasmids containing various reconstructions of the original yeast DNA insert. Examination of the expression of the cloned yeast PGK gene in both E. coli and yeast has shown that functional enzyme is synthesized from the cloned gene in yeast, but not in E. coli. PMID- 6254993 TI - Solubilization and characterization of adrenal and uterine angiotensin II receptors after photoaffinity labeling. AB - The physical characteristic of the receptors for angiotensin II in dog adrenal cortex and uterus were determined after affinity labeling. 125I-nitro-5-azido benzoyl-angiotensin II, a photosensitive angiotensin II analogue which retained aldosterone-stimulating activity, was used to couple the octapeptide specifically and irreversibly to its membrane receptors. After solubilization with Triton X 100, the covalent hormone . receptor complex was analyzed by gel filtration and sucrose density gradient centrifugation. Two radioactive species were consistently observed, with calculated Mr values of 126,000 +/- 10,000 and 64,500 +/- 11,000. the elution profiles of solubilized adrenal and uterine particles were almost identical. When the solubilized complexes were subjected to sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis, a single radioactive band was detected upon autoradiography, with Mr - 65,000 +/- 6,000 for adrenal cortex and 68,000 +/- 7,000 for myometrium. These results indicate that the receptors for angiotensin II in adrenal cortex and uterus are composed of two subunits of similar molecular weight, and that the common functional properties of the receptors from both tissues are probably related to their similar physicochemical characteristics. PMID- 6254994 TI - Diagnosis of eosinophilic granuloma of bone by cytology, histology, and electron microscopy of transcutaneous bone-aspiration biopsy. AB - The cytological, histological, and ultrastructural morphology of transcutaneous bone aspirates from five patients with eosinophilic granuloma of bone were studied. Use of this combined approach enabled us to make a definitive diagnosis of eosinophilic granuloma from a small quantity of tissue without having to resort to open biopsy. By light microscopy, eosinophilic granuloma is composed of a polymorphous infiltrate of characteristic lobulated histiocytes, eosinophils, polymorphonuclear leukocytes, and giant cells. Each specimen examined ultrastructurally demonstrated the characteristic Langerhans granule-containing histiocyte. Eosinophilic granuloma is a benign lesion which is readily diagnosed by this technique, and more aggressive diagnostic procedures usually are not warranted. PMID- 6254995 TI - Nature of permeability changes in membrane of HeLa cells adsorbing Sendai virus. AB - Adsorption of Sendai virus to HeLa cells induced in them an increased permeability to K+, Na+, Ca++, deoxyglucose, but not to fluorescein. The stimulation of uptake of 42K was temperature-dependent, did not occur below 15 degrees C, and was not inhibited by ouabain. The virus-induced increase in the uptake and release of 42K and of 3H deoxyglucose could not be mimicked by treatment of cells with linoleic acid, a procedure which increased the fluidity of the cellular membranes. The stimulatory effect of 0.5 mM ATP on the release of deoxyglucose was enhanced several fold in the presence of Sendai virus. These results seem to indicate the possible involvement of membranal enzymes such as e.g. protein kinase in the permeability changes induced by Sendai virus. PMID- 6254997 TI - Ionophore-induced disassembly of blood platelet microtubules: effect of cyclic AMP and indomethacin. AB - Cytoplasmic calcium levels are believed to be important in blood platelet activation. Upon activation, the discrete marginal microtubule band, which maintains the discoid shape of non-activated platelets, becomes disrupted. Present studies demonstrate that the extent of assembly of the marginal microtubule band is related to cytoplasmic calcium levels. The divalent cationophore, A23187, causes platelet aggregation, secretion, and contraction by promoting calcium transport from intraplatelet storage sites into the cytoplasm. A23187 caused disassembly of platelet microtubules. Quantitation of electron micrographs revealed that numbers of microtubules were reduced by approximately 80% after A23187 treatment. Secondly, assembled microtubules in homogenates of platelets, in which microtubules were stabilized prior to homogenization, were decreased in favor of free tubulin in A23187-treated platelets. Thirdly, A23187 increased 14C-colchicine binding by intact platelets; this also indicated a shift in the microtubule subunit equilibrium to favor free, colchicine-binding tubulin subunits. In control experiments, A23187 did not affect the stability of platelet tubulin, the colchicine binding reaction, or the total tubulin content of platelets. Stimulation of colchicine binding depended on A23187 concentration (0.05-0.5 microM) and did not require extracellular calcium. A23187-stimulation of colchicine binding was blocked by dibutyryl cyclic AMP (0.80 mM) and/or 3 isobutyl-1-methylxanthine (50 microM) and by indomethacin (10 microM). Cyclic AMP or indomethacin also interferes with A23187-induced platelet activation, but indomethacin is not likely to completely inhibit the perturbation of intraplatelet calcium gradients by A23187. It is suggested that A23187-induced microtubule disassembly may be an indirect effect of calcium on microtubules. PMID- 6254996 TI - Decay of hormone responsiveness in mouse melanoma cells in culture as a function of cell density. AB - Cloudman S91 mouse melanoma cells lose their ability to demonstrate an MSH induced increase in tyrosinase activity as cell density increases. This loss in hormone responsiveness occurs before confluency is reached and cannot be reversed by exposure of cells to increasing concentrations of MSH. The failure of high density cultures to respond to MSH is apparently not the result of an inability of MSH to stimulate cAMP production, since either low- or high-density cultures exposed to MSH demonstrate equivalent increases in intracellular levels of cAMP. Further, neither theophylline (1mM), dibutyryl cyclic AMP (10(-4)M), or prostaglandin E1 (10(-6)M) is effective in stimulating tyrosinase activity in melanoma cells cultured at densities exceeding 6 X 10(4) cells/cm2. This finding suggests that the decay of hormone responsiveness occurs at a cellular site distal to cAMP production. The decrease in tyrosinase stimulation by MSH as cell density increases is also apparently not the result of an increase in activity of any soluble inhibitor of the enzyme, for cytosol preparations from high-density cultures (10(5) cells/cm2) fail to inhibit tyrosinase activity in cell homogenates from low-density cultures treated with MSH. PMID- 6254998 TI - The growth requirements of SV40 virus transformed Balb/c-3T3 cells in serum-free monolayer culture. AB - The growth requirements of SV40 transformed Balb/c-3T3 cells have been studied in the absence of serum. For growth in serum-free medium, the cells require (i) insulin, (ii) transferrin, and (iii) cis-unsaturated fatty acids added in combination with fatty acid free bovine serum albumin. The growth rate, saturation density, and morphology of cells grown in this serum-free medium are the same as those of cells grown in serum supplemented medium. This mixture also supports the growth of SV40 transformed Swiss-3T3 cells and SV40 transformed primary mouse embryo cells, but does not support the growth of untransformed Balb/c-3T3 cells. The addition of fibronectin to this mixture allows routine subculture, repeated passage, and indefinite propagation of SV40 transformed Balb/c-3T3 cells. Cells grown in this medium for a period of two months retain their ability to induce tumors when injected into athymic nude mice. PMID- 6254999 TI - The deformability of BHK cells and polyoma virus-transformed BHK cells in relation to locomotory behaviour. AB - Several aspects of the behaviour of polyoma virus-transformed BHK cells in culture have suggested that they are more deformable than BHK cells. This possibility was tested by applying negative pressure at the cell surface by means of a micropipette. It was found that PyBHK cells in early mitosis are twice as deformable as BHK cells in the same stage. In addition, the taut, non-ruffling margins of both cell types when fully spread are much less deformable than the extending, ruffling leading lamella. The degree of deformability of these cells is correlated with the distribution and organization of microfilaments and consistent with this, deformability increases greatly in the presence of cytochalasin B. The significance of deformability studies such as these is discussed. PMID- 6255000 TI - Regulation of macrophage lysosomal enzyme secretion: role of arachidonate metabolites, divalent cations and cyclic AMP. AB - We have investigated the role in macrophage lysosomal enzyme release of arachidonate metabolites, extracellular divalent cations and cyclic AMP (cAMP) which modulate secretion in other cell types. Lysosomal enzyme secretion induced by zymosan was accompanied by release of malondialdehyde (MDA), which is derived from arachidonic acid via prostaglandin synthase. Blockade of MDA formation, by aspirin or indomethacin, was associated with only a small inhibitory effect on lysosomal enzyme release by zymosan: arachidonate metabolites thus play only a minor role in mediating macrophage lysosomal enzyme release. Zymosan-induced secretion of lysosomal enzymes from macrophages did not require extracellular magnesium or calcium although release was enhanced by magnesium and inhibited by calcium. These effects may be related to an influence of the ions on phagocytosis. Elevation of intracellular divalent cation concentrations, by ionophore A23187, induced release of lysosomal enzymes but this was a result of cell lysis. Adenylate cyclase stimulants and dibutyryl cAMP produced slight inhibition of zymosan-induced lysosomal enzyme release. Aminophylline and papaverine caused more marked inhibition but their effects may be due to actions independent of phosphodiesterase inhibition. Our data indicate that arachidonate metabolites and cAMP do not play a major role in regulating zymosan-induced enzyme release from macrophages. Extracellular calcium and magnesium may modulate secretion but the role of intracellular divalent cations remains to be established. We conclude that macrophage lysosomal enzyme secretion is controlled by regulatory mechanisms different from those which control similar degranulation processes in other cell types. PMID- 6255001 TI - Effect of parathyroid hormone on 1,25-dihydroxyvitamin D formation in type I pseudohypoparathyroidism. AB - The role of parathyroid hormone (PTH) and cAMP in the hydroxylation of 25 hydroxyvitamin D to 1,25-dihydroxyvitamin D [1,25-(OH)2D] was explored in two young male volunteers and a patient with pseudohypoparathyroidism type I. Parathyroid extract infusion resulted in a prompt and distinct increase in the plasma levels of cAMP and the urinary excretion of the nucleotide in the normal controls, whereas there was only a negligible increase in the patient. In both the patient and the control subjects, the serum concentration of 1,25-(OH)2D showed a distinct increase after the parathyroid extract infusion. The responses were similar in magnitude and were apparent after 2 h, with a further rise 4 h in the patient and one of the controls, whereas the other control subject only responded after 4 h. The findings are consistent with the assumption that a normal renal cAMP response to PTH is not essential for the PTH stimulation of the renal 25-hydroxyvitamin D-1 alpha-hydroxylase. The two other dihydroxymetabolites of vitamin D, 24,25-(OH)2D and 25,26-(OH)2D, showed no consistent response to the PTH infusion in either the controls or the patient. PMID- 6255002 TI - Serotonin stimulates adenosine 3',5'-monophosphate accumulation in parathyroid adenoma. AB - The effect of serotonin on cAMP accumulation in parathyroid adenoma tissue from patients with primary hyperparathyroidism was studied in vitro. Incubation with 10(-5) M serotonin elicited a marked increase (of 90--150%) in cAMP content in slices of parathyroid adenoma tissue. This stimulatory effect of serotonin was already apparent after 2 min of incubation; stimulation by serotonin was dose dependent, with the highest stimulation being achieved at 10(-4) M serotonin. The serotonin antagonists, methylsergide and cinanserin, in concentrations equimolar to serotonin completely blocked the stimulatory effect of serotonin on cAMP increase. The serotonin content in surgically removed parathyroid adenoma tissue, as determined by fluorometric assay, was 6.4 +/- 1.2 pmol/mg wet wt (approximately 0.8 x 10(-5) M). The present observations demonstrate that parathyroid adenoma tissue has a high content of serotonin, and serotonin stimulates cAMP accumulation in this tissue. Since cAMP acts as a mediator of parathyroid hormone (PTH) release, our results suggest that serotonin could be one of the factors regulating PTH secretion and/or contributing to PTH hypersecretion in various forms of primary hyperparathyroidism. PMID- 6255003 TI - Histamine receptors on dispersed parathyroid cells from pathological human parathyroid tissue. AB - The effects of histamine on cAMP accumulation and parathyroid hormone (PTH) release were studied in dispersed cell preparations from pathological parathyroid tissue of 13 patients with primary hyperparathyroidism. Histamine stimulated cAMP accumulation 1.4- to 110-fold in a dose- and time-dependent manner. The increased cAMP content was inhibited by the H2 antagonist cimetidine and the H1 antagonist promethazine, with Ki values of 0.14--0.46 and 0.2--0.37 micrometer, respectively. Moreover, in one cell preparation, the H2 agonist dimaprit stimulated cAMP accumulation 2- to 3-fold, while the H1 agonist 2 pyridylethylamine had no effect on cAMP levels. The potent alpha-and beta adrenergic antagonists phentolamine and propranolol did not inhibit histamine stimulated cAMP accumulation significantly. Histamine also caused a dose- and time-dependent increase in PTH release, with a Ka in reasonable agreement with that for cAMP accumulation (0.5--1 vs. 3 micrometer, respectively), indicating that enhanced cAMP accumulation was linked to increased secretion. These results indicate that pathological human parathyroid cells have histamine receptors, probably H2 in subtype, which mediate enhanced cAMP accumulation and PTH release. PMID- 6255004 TI - Plasma norepinephrine levels are influenced by sodium intake, glucocorticoid administration, and circadian changes in normal man. PMID- 6255005 TI - Effect of estrogen on calcium absorption and serum vitamin D metabolites in postmenopausal osteoporosis. AB - Osteoporotic women have decreased calcium absorption and decreased serum 1,25 dihydroxyvitamin D [1,25-(OH)2D] and are usually in negative calcium balance. Estrogen therapy improves calcium balance in patients with postmenopausal osteoporosis. In birds, estrogen administration increases the conversion of 25 hydroxyvitamin D (25OHD) to 1,25-(OH)2D. To determine if estrogen therapy affects vitamin D metabolism in human subjects, we studied 21 osteoporotic women before and after 6 months of treatment. We compared groups treated with either placebo (9 patients) or conjugated equine estrogen (1.2-2.5 mg/day; 12 patients). Fractional calcium absorption (mean +/- SE) was unchanged after treatment with placebo (0.51 +/- 0.03 to 0.52 +/- 0.01) but increased after treatment with estrogen (0.53 +/- 0.02 to 0.65 +/- 0.04; P < 0.005). The increase after estrogen was similar to the increase observed in 10 additional osteoporotic women treated for 6 months with a small dose of 0.5 microgram/day 1,25-(OH)2D (0.54 +/- 0.03 to 0.68 +/- 0.04; P < 0.005). Serum 1,25-(OH)2D was unchanged after treatment with placebo (27.5 +/- 1.3 to 27.6 +/- 1.7 pg/ml) but increased after treatment with estrogen (23.6 +/- 2.7 to 33.2 +/- 3.7 pg/ml; P < 0.005). Serum immunoreactive parathyroid hormone (PTH) increased (23.0 +/- 4.2 to 32.7 +/- 4.6 microliter eq/ml; P < 0.05) after estrogen but not after placebo treatment. After treatment with estrogen, the increases in serum immunoreactive PTH and serum 1,25-(OH)2D were correlated (r = 0.68; P < 0.05), and the increases in serum 1,25-(OH)2D and calcium absorption were highly correlated (r = 0.89; P < 0.001). We conclude that estrogen treatment increases calcium absorption in postmenopausal osteoporosis by increasing serum 1,25(OH)2D. This effect appears to be mediated indirectly through stimulation of renal 1 alpha-hydroxylase by increased serum PTH. PMID- 6255006 TI - Steroid biosynthesis by isolated human ovarian follicular cells in vitro. AB - Cultured thecal preparations from human ovarian follicles obtained from patients during the follicular phase of the menstrual cycle produced large amounts of delta 4-androstenedione and smaller amounts of testosterone and other androgens when stimulated by hCG, (Bu)2cAMP, and prostaglandin E2, but not when stimulated by FSH. Prostaglandin E2 also stimulated thecal cAMP production under the same conditions. By contrast, androgen production by granulosa cells was negligible with or without gonadotropins in the culture medium. Granulosa cells also did not produce 17 beta-estradiol, even when exposed to FSH and hCG, unless supplied with exogenous delta 4-androstenedione. On the other had, thecal, preparations did not produce significant amounts of 17 beta-estradiol even in the presence of FSH, hCG, and relatively large amounts of exogenous delta 4-androstenedione. These observations suggest that delta 4-androstenedione produced by LH or hCG stimulated thecal cells is the main substrate for the synthesis of 17 beta estradiol by FSH-stimulated granulosa cells in vivo. PMID- 6255007 TI - Demonstration of 1,25-dihydroxyvitamin D3 receptors in human skin biopsies. AB - In this study we report the demonstration of receptors for 1,25-(OH)2 vitamin D3 in fresh and cultured human skin. Cultured fibroblasts grown from infant foreskin exhibit a binding site which by Scatchard analysis had a Kd for [3H]1,25-(OH)2D3 of 0.2 nM and an Nmax of approximately 40 fmol/mg cytosol protein. On sucrose density gradients the receptor sediments at 3.2S. Receptors could also be identified in skin biopsies from adult patients when assayed either in fresh epidermis or cultured keratinocytes and dermal fibroblasts. The human receptors are similar to rodent receptors assessed in classical target organs such as intestine, bone and kidney. The findings that receptors can be measured in cultured human skin after several arterial passages indicates that skin biopsy may provide a means of assessing the 1,25-(OH)2D3 receptor status of patients. PMID- 6255008 TI - The presence of lactogen receptors in human chorion laeve. AB - Lactogen receptors have been identified in human chorion laeve and possibly placenta but not other periplacental tissues. The receptors show the same hormonal specificity, and similar binding parameters (affinity 0.47 x 10(9) l/m, capacity 175 fmol3/mg) to lactogen receptors in mammary gland and liver. The presence of these receptors, suggests they may play a role in mediating an action(s) of amniotic fluid prolactn in chorion laeve, such as osmoregulation. PMID- 6255009 TI - Clearance of thrombin from circulation in rabbits by high-affinity binding sites on endothelium. Possible role in the inactivation of thrombin by antithrombin III. AB - The clearance of (125)I-thrombin and diisopropylphosphoryl-(125)I-thrombin (DIP thrombin) from the circulation in rabbits was studied. When given either intraarterially or intravenously, DIP-thrombin, which is active-site blocked, was approximately 90% cleared from the circulation by 1 min, the time of earliest sampling, indicating a large first-pass effect. DIP-thrombin given intravenously is found predominantly in the lungs, whereas DIP-thrombin injected into the aortic arch is distributed diffusely in approximate proportion to the blood supply. Renal artery, femoral artery, ear artery, left atrium, and portal vein infusions demonstrate that kidney, muscle, ear, heart, and liver, respectively, can remove DIP-thrombin from the circulation. These data imply that the clearance of DIP-thrombin is not a function of a specific organ but of the vascular bed per se. The clearance of DIP-thrombin was reversible since injection of 0.5 mg of unlabeled DIP-thrombin 10 min after the injection of a tracer dose of DIP-(125)I thrombin resulted in the rapid reappearance of the DIP-(125)I-thrombin into the circulation. In addition, the clearance of DIP-thrombin was saturable, i.e., clearance of DIP-(125)I-thrombin was inhibited by unlabeled DIP-thrombin in a dose-dependent fashion. In vivo Scatchard analysis of the saturation of the clearance process demonstrated that DIP-thrombin can be removed by binding to high-affinity binding sites, since dissociation constants (K(D)) of 10 and 13 nM were obtained for human and bovine DIP-thrombin, respectively. In contrast to DIP thrombin, approximately 75% of the radioactivity associated with active thrombin remained in the circulation at 1 min. By 10 min 55% of (125)I-thrombin had been removed from the circulation, and essentially all of the radioactivity can be accounted for in the liver. Sodium dodecyl sulfate-polyacrylamide gel radioelectrophoresis of plasma samples taken after injection of (125)I-thrombin demonstrated that all of the active thrombin was converted to covalent thrombin antithrombin III complex by the time of initial sampling (30 s). The in vitro conversion of (125)I-thrombin to thrombin-antithrombin III complex was considerably slower (50+/-5% conversion at 30 s). The simultaneous injection of excess unlabeled DIP-thrombin inhibited the rate of formation of (125)I-thrombin antithrombin III complex formation in vivo (but not in vitro), which suggests that the binding of active thrombin to the high affinity binding sites is required for the rapid inactivation of thrombin in vivo. We propose that (a) thrombin in the circulation binds to active site-independent high-affinity binding sites on the endothelial cell surface; (b) the inactivation of thrombin by antithrombin III is faster in vivo than in vitro because the high-affinity binding sites, present in a high concentration in the microcirculation, catalyze the reaction; (c) thrombin-antithrombin III complexes are selectively removed by the liver. PMID- 6255010 TI - Role of vitamin D glucosiduronate in calcium homeostasis. AB - Evidence has been presented suggesting the presence of vitamin D(3) 3beta glucosiduronate and 1,25-dihydroxyvitamin D(3) glucosiduronate in rat bile. To evaluate the role of vitamin D glucosiduronates in calcium and phosphorus homeostasis, we synthesized vitamin D(3) 3beta-glucosiduronate and tested its biological activity in calcium- and vitamin D-deficient rats. After the intravenous administration of vitamin D(3) 3beta-glucosiduronate to rats maintained on a low calcium diet, there was an increase in duodenal calcium transport and an increase in serum calcium. Vitamin D(3) 3beta-glucosiduronate, however, was less active than equimolar amounts of vitamin D(3). At doses of less than 0.65-1 nmol per rat, the conjugate exhibited no activity. When vitamin D(3) 3beta-glucosiduronate was administered to vitamin D-deficient rats, 25 hydroxyvitamin D was detected in the serum; the increase in serum 25 hydroxyvitamin D levels was less than that observed after the administration of an equimolar amount of vitamin D(3). Vitamin D(3) 3beta-glucosiduronate showed no detectable activity in the induction of calcium binding protein in chick embryonic duodena, a system in which no endogenous steroid beta-glucuronidase activity is detectable. These data demonstrate that vitamin D(3) 3beta glucosiduronate is biologically active in vivo and that the observed activity is due to hydrolysis of the conjugate to vitamin D(3). As vitamin D(3) 3beta glucosiduronate is excreted in the bile of rats, it is possible that this conjugate is reutilized in vivo after hydrolysis to free vitamin D(3). These results suggest the existence of a mechanism for reutilization of the biliary products of vitamin D(3). PMID- 6255012 TI - NAD(P)H oxidase activity in human neutrophils stimulated by phorbol myristate acetate. AB - Phorbol myristate acetate activated in normal human neutrophils a single enzymatic entity that was dormant in unstimulated cells, optimally active at pH 7.0, and capable of oxidizing either NADH or NADPH, producing NAD(P)+ and superoxide (O27). Comparative fluorometric and spectrophotometric measurements supported the stoichiometry NAD(P)H + 20(2) leads to NAD(P)+ + 20(27) + H+. the seemingly considerable NAD(P)+ production at pH 5.5 and 6.0 was due largely to nonenzymatic oxidation of NAD(P)H by chain reactions initiated by HO27 (perhydroxyl radical), the conjugate acid of O27. This artifact, responsible for earlier erroneous assignments of an acid pH optimum for NAD(P)H oxidase, was prevented by including superoxide dismutase in fluorometric assays. NAD(P)H oxidase was more active towards NADPH (Km = 0.15 +/- 0.03 mM) than NADH (Km = 0.68 +/- 0.2 mM). No suggestion that oxidase activity was allosterically regulated by NAD(P)H was seen. Phorbol myristate acetate-induced O27 production was noted to be modulated by pH in intact neutrophils, suggesting that NAD(P)H oxidase is localized in the plasma membrane where its activity may be subject to (auto) regulation by local H+ concentrations. PMID- 6255011 TI - Immunoreactive beta-endorphin and adrenocorticotropin in human cerebrospinal fluid. AB - To elucidate the significance of beta-endorphin in human cerebrospinal fluid (CSF), CSF levels of beta-endorphin-like immunoreactivity (beta-EP-LI) in various diseases were determined by a specific radioimmunoassay and compared with simultaneously determined ACTH-like immunoreactivity (ACTH-LI) levels in CSF. CSF beta-EP-LI and ACTH-LI in the control group, consisting of 5 normal subjects and 19 patients with nonendocrine diseases, were 22.2+/-1.3 and 14.6+/-0.4 fmol/ml, respectively. CSF levels of these peptides in patients with schizophrenia (n = 19) and acromegaly (n = 10) were not significantly different from those in the control group. Patients with Cushing's disease (n = 7) had significantly lower CSF beta-EP-LI and ACTH-LI levels than those in the control group. Four of them showed a parallel increase in CSF beta-EP-LI and CSF ACTH-LI levels after the complete removal of pituitary microadenomas (P < 0.05). Gel chromatography of CSF beta-EP-LI from a normal volunteer, a control patient, and one patient each with catatonia, Nelson's syndrome, Cushing's syndrome (adrenal adenoma), and acromegaly gave similar patterns consisting of three peaks with the elution positions comparable to those of authentic beta-endorphin, beta-lipotropin, and possibly their precursor molecule. Gel chromatographic patterns of CSF beta-EP-LI and ACTH-LI were compared in a normal volunteer. The first peaks of beta-EP-LI and ACTH-LI eluted at the same position and the second peak of ACTH-LI coincided with the elution position of authentic ACTH.CSF beta-EP-LI and ACTH-LI levels determined every 5 min over a period of 80 min in three normal volunteers did not show moment-to-moment variability.A significant correlation (r = 0.75, P < 0.001) was seen between CSF beta-EP-LI and ACTH-LI levels in normal subjects and patients studied (n = 73). This suggests that beta-endorphin and ACTH in human CSF share the common regulatory mechanism in normal and pathologic conditions. PMID- 6255013 TI - Potassium and angiotensin II increase the concentrations of phosphatidic acid, phosphatidylinositol, and polyphosphoinositides in rat adrenal capsules in vitro. AB - We examined the effects of K+ and angiotensin II, the major regulators of aldosterone secretion, on phospholipid metabolism during incubation of glomerulosa-rich, adrenal capsules. Addition of increasing amounts of K+ and angiotensin II to the incubation media elicited progressive increases in corticosterone production and capsular concentrations of phosphatidic acid, phosphatidyl-inositol, and polyphosphoinositides. These effects are similar to those previously reported for ACTH in the whole adrenal cortex. A common mechanism, i.e., activation of the phosphatidate-polyphosphoinositide cycle, may be operative in the action of steroidogenic agents in their target tissues. PMID- 6255014 TI - Mixed hepatoblastoma in the adult: case report and review of the literature. AB - A case of mixed hepatoblastoma in a woman is described. A survey of the English literature reveals 13 cases acceptable as mixed hepatoblastoma; these have been described and published under a variety of names. Difficulties in nomenclature and the histology of these cases are discussed. Diagnosis depends on the identification of both malignant mesenchymal and malignant epithelial elements. The former include myxoid connective tissue resembling primitive mesenchyme and areas resembling adult fibrosarcoma. Mature fibrous tissue with calcification and bone formation may be seen. Epithelial areas show tissue resembling fetal liver, poorly differentiated epithelial cells, and/or areas of adenocarcinoma. The current view on histogenesis is also given. PMID- 6255016 TI - An outbreak of calicivirus infection in a mother and baby unit. AB - A small outbreak of infection due to a calicivirus occurred in a mother and baby unit. All the infants showed evidence of infection but the clinical features varied. None of the staff or mothers showed evidence of illness, and antibody studies indicated past experience of this virus. PMID- 6255015 TI - Anti-collagen antibodies in sera from rheumatoid arthritis patients. AB - Anti-cartilage antibodies, demonstrable by immunofluorescence, were found in 3.3% of rheumatoid arthritis patients. In most of these patients antibodies to type II collagen were detected. In specificity studies on these anti-collagen antibodies, they appeared to be type specific, showing no reaction with collagen types I and III. Denatured type II collagen reacted much less well than native type II, but isolated peptides from different regions of the collagen molecule were differentiated by individual sera. Removal of the glycoside side chains from native type II collagen had no effect on its antigenicity. The findings suggest that these patients produce highly specific antibodies which react with the triple helix of type II collagen. PMID- 6255017 TI - Hypothesis. Cyclic AMP and its receptor protein in tumor growth regulation in vivo. AB - A working hypothesis is presented to elucidate the action of cyclic AMP in the regulation of tumor growth in vivo. The formation and nuclear translocation of a complex consisting of cyclic AMP, its receptor binding protein, and the catalytic unit of protein kinase are the indispensable events necessary to trigger the regression of hormone-dependent mammary tumors. If the integrity of the cyclic AMP receptor molecule is not preserved and the cyclic AMP concentration is not physiological, the above processes do not occur and tumors remain hormone unresponsive. It is therefore postulated that arrest of tumor growth in vivo depends upon the structural integrity of the cyclic AMP receptor protein and the optimum cellular concentration of cyclic AMP, which make possible the formation and nuclear translocation of the cyclic AMP receptor complex. PMID- 6255018 TI - Is extracellular calcium required for insulin action? AB - Isolated hepatocytes and isolated adipocytes incubated in the absence of added calcium ions respond to insulin with a decrease in tissue cyclic AMP levels, and an increase in low Km phosphodiesterase activity. Isolated hepatocytes also showed a diminution of glucagon stimulated glucose output in response to insulin, while adipocytes responded with increased rates of glucose oxidation, lipid synthesis and decreased glycerol output. These responses to insulin are the same as those seen when the cells are incubated in buffers containing physiological concentrations of calcium ions. When extracellular concentrations of calcium ions were made extremely low by using either gelatine or albumin which had been pretreated to remove calcium, and/or the incubation buffers contained EGTA, both the hepatocytes and adipocytes continued to respond to insulin. These results suggest that extracellular calcium ions are not required for insulin action. PMID- 6255019 TI - Methyl 5'-(6-aminopurin-9-yl)-5'-deoxy-beta-D-ribofuranoside 2',3'-cyclic monophosphate: a novel, biologically active, structural analogue of cyclic AMP. AB - A novel structural analogue of cyclic AMP has been synthesized. This compound has been found to activate protein kinase from skeletal muscle (Ka 5.0 microM). It is virtually resistant to degradation by beef heart cAMP phosphodiesterase. It is an inhibitor of this enzyme with an [I]50 of 47.0 microM. The proliferation of cancer cells (HT-29) is inhibited by this compound. It represents the first example of a 2',3'-cyclic nucleotide with marked biological activity. PMID- 6255020 TI - Studies of functional domains of the regulatory subunit from cAMP-dependent protein kinase isozyme I. AB - Homogenous regulatory subunit from rabbit skeletal muscle cAMP-dependent protein kinase (isozyme I) was partially hydrolyzed with low (1 g/1300 g) or high (1 g/6 g) concentrations of trypsin. After treatment with low trypsin two main peptides (Mr = 35,000 and 12,000) were produced. The cAMP-binding activity (2 mol cAMP/mol of subunit monomer) was recovered in the monomeric Mr = 35,000 peptide. The ability of either fragment to inhibit catalytic subunit activity was lost. Treatment of the regulatory subunit with a high concentration of trypsin yielded three main fragments (Mr = 32,000, 16,000, and 6,000) which could be resolved by Sephadex G-75 and purified further on DEAE-cellulose columns. One of the peptides (Mr = 32,000) bound 2 mol cAMP/mol fragment. The Mr = 16,000 fragment was very labile and bound cAMP with an undetermined stoichiometry. Cyclic AMP dissociation curves for the native regulatory subunit and its Mr = 32,000 component were similar and suggested the presence of two nonidentical binding sites in each monomer. Using the same procedure, the Mr = 16,000 fragment or homogenous cGMP dependent protein kinase appeared to contain a single type of binding site. Purified Mr = 32,000 fragment was readily converted to the Mr = 16,000 fragment using high trypsin as assessed by protein bands on SDS-disc gels or by following transfer of radioactivity from Mr = 32,000 peptide covalently labeled with 8-N3 [32P] cAMP to radiolabeled Mr = 16,000 fragment. The smallest regulatory subunit fragment (Mr = 6,000) did not bind cAMP, but was dimeric and could be part of the dimerization domain in the native protein. A model is presented to explain the possible structural-functional relationships of the regulatory subunit. PMID- 6255021 TI - Fiber sources for complete calf starter rations. AB - Complete calf starter rations containing either 1) alfalfa hay, 2) cottonseed hulls, or 3) alfalfa-beet pulp as sources of fiber were fed to Holstein heifer calves at two locations on a limited milk program from 3 days to 12 wk of age. Rations were isonitrogenous and similar in content of crude fiber and acid detergent fiber. Although growth and development were normal on all rations, calves fed the cottonseed hull ration consumed more starter and gained more body weight than calves fed the other sources of fiber. The similarity of feed efficiencies, rumen pH, and molar ratios of volatile fatty acids between rations indicated no appreciable differences in rumen development or function. The growth response of calves fed the cottonseed hull ration appeared to be a result of better ration acceptability for which no reason was evident. Calves raised at Puyallup gained more body weight than calves at Pullman, and these gains were made more efficiently. These location effects may be related to seasonal differences and greater demands for production of body heat. Although the incidence of scours was less for calves fed alfalfa hay starter, the incidence and severity of bloat were higher for that ration. PMID- 6255022 TI - The effect of hemodialysis on levels of cyclic nucleotide-associated hormones in patients with chronic renal failure. AB - In order to determine the molecular basis for the loss of catecholamine responsiveness in skeletal muscle in chronic azotemia, plasma and serum levels of catecholamines and other hormones whose mechanisms of action are associated in part with cyclic nucleotide mediation were assessed in 37 patients with chronic azotemia. Samples were obtained prior to and immediately following conventional hemodialysis. Plasma epinephrine and norepinephrine levels in patients predialysis were increased 50% and 25% respectively compared to control subjects. Levels of insulin, prolactin, aldosterone and renin were also in creased in azotemic patients prior to dialysis. Conventional hemodialysis reduced serum levels of growth hormone, but had no effect of the elevated levels of all other hormones found in patients predialysis. In particular, plasma epinephrine and norepinephrine levels were unaffected by hemodialysis. Despite these findings, hemodialysis did reduce to normal levels the elevated plasma levels of cyclic AMP and cyclic GMP observed in uremic subjects predialysis. These data are consistent with increased adrenergic outflow in patients with chronic azotemia, and suggest a mechanism of homologous desensitization of the catecholamine receptor adenylyl cyclase unit in chronic azotemia. PMID- 6255024 TI - SIDS--a new perspective: immunologic-mediated pulmonary disease. PMID- 6255023 TI - Will improvement in the socioeconomic status of women increase their cardiovascular morbidity and mortality? PMID- 6255025 TI - Stresses on Asian women physicians. PMID- 6255026 TI - Update on drug therapy: VI. Penicillinase-resistant penicillins. PMID- 6255027 TI - Interesting nuclear medicine and computed tomography (CT) scans. PMID- 6255028 TI - Slow inhibitory postsynaptic potentials and hyperpolarization evoked by noradrenaline in the neurones of mammalian sympathetic ganglion. AB - Slow IPSPs evoked in the neurones of rabbit isolated superior cervical ganglion by repetitive orthodromic stimulation, and a response evoked in the neurones of this ganglion by perfusion of noradrenaline, were studied using intracellular microelectrodes. Slow IPSPs were observed in 36% of neurones studied, and when investigated after treatment with D-tubocurarine and neostigmine, had a mean amplitude of 4.4 +/- 0.2 mV (mean +/- S.E.) and duration of 5 sec to 1.5 min. Two types of slow IPSPs occurring in different neurones were found. The slow IPSP of the first type was followed by a decrease in cell input resistance, was increased by depolarization and decreased by hyperpolarization of the membrane, with the reversal potential, if estimated by extrapolation method, equal to -77.8 +/- 3.3 mV. The slow IPSP of the second type was not followed by any change in cell input resistance, was increased by hyperpolarization and decreased by depolarization. The slow IPSP of the second type was reversibly blocked by phentolamine (1.4 X 10(-4) M). Noradrenaline (1 X 10(-4) M) evoked hyperpolarization or hyperpolarization followed by depolarization in 55% of the neurones studied. Hyperpolarization evoked by noradrenaline had a mean amplitude to 5.0 +/- 0.2 mV, was not followed by any change in cell input resistance, was reversibly blocked by phentolamine (1.4 X 10(-4) M), and was decreased by both depolarization and hyperpolarization of the cell membrane. It has been concluded that there are two groups of neurones in superior cervical ganglia, different with respect to the ionic mechanisms underlying the slow IPSP. In the first group of neurones the slow IPSP is probably due to an increase in potassium permeability of the membrane. The ionic mechanisms underlying the slow IPSP in the second group of neurones of noradrenaline-induced hyperpolarization remain unclear. PMID- 6255029 TI - Fiber and gastrointestinal microecology. AB - The gastrointestinal tract contains a unique microecology. Microorganisms living in the mouth, stomach, and most importantly in the small and large intestines produce enzymes which help metabolize certain ingested foods, as well as maintain important body homeostatic mechanisms such as the bile salt enterohepatic circulation. Recent awareness of the importance of poorly digested foods such as cellulose, hemicellulose, pectins, and lignins, as well as selectively absorbed long-chain polysaccharides, has stressed the importance of the relationship of food to the microflora. This intestinal microecology has definite effects on the human host in cholesterol metabolism, glucose tolerance, and may explain such diseases as carcinoma. The exacting details of the intestinal microecology need further elaboration. PMID- 6255030 TI - Morphologic probes of polypeptide hormone receptor interactions. AB - Polypeptide hormones, growth factors, and a variety of other naturally occurring ligands bind specifically to receptors on the cell surface. At physiologic temperatures these ligands are internalized by cells and associate intracellularly with lysosomes. Receptor-mediated internalization provides a simple mechanism that may act to couple receptor-mediated hormone degradation with receptor-medicated receptor regulation. PMID- 6255031 TI - Polypeptide hormone receptors in vivo: demonstration of insulin binding to adrenal gland and gastrointestinal epithelium by quantitative radioautography. AB - A tissue-screening survey employing quantitative radioautography was carried out at 2 min after the intravascular injection of 125I-insulin into laboratory rats. The results revealed a substantial binding of insulin to cells forming the proximal convoluted tubule in kidney, hepatocytes of liver, acinar cells of the pancreas, parenchymal cells of the adrenal cortex and medulla, and epithelial cells of the gastrointestinal tract. Control experiments indicated that this binding was due to a specific interaction with the insulin receptor, except in the case of kidney where the binding was shown to be nonspecific. Although the major target for insulin action (liver) clearly demonstrated specific insulin binding, several other classical targets (adipocytes, skeletal, cardiac, and smooth muscle cells) showed no specific 125I-insulin binding and therefore indicated the limits of sensitivity of the in vivo radioautographic method. Nevertheless, the working hypothesis of a direct correlation of insulin receptor density with insulin action points to the hitherto unemphasized targets of pancreas, adrenal gland, and gastrointestinal tract as major sites of insulin action in the body. PMID- 6255032 TI - Surgical treatment in Krukenberg's tumour. PMID- 6255033 TI - [Proceedings of the symposium of the Gustave-Roussy Institute on malignant germinal tumors of the testis]. PMID- 6255034 TI - Effects of cholera toxin on ornithine decarboxylase activity in mouse skin. AB - The subcutaneous injection of cholera toxin into adult mice resulted in a sustained increase in cyclic AMP levels in mouse epidermis after a lag period of about 2 hr. An increase in ornithine decarboxylase activity occurred between 7 and 10 hr, which was maintained for at least 10 hr. The increase in decarboxylase activity was localized to the area of epidermis visually affected by cholera toxin and was unaffected by hypophysectomy, suggesting a direct effect of the toxin on the epidermal cells. The subcutaneous injection of cholera toxin also led to an increase in cyclic AMP levels in newborn mouse skin. In contrast to adult mice, newborn mouse skin contained high basal activities of ornithine decarboxylase in both the epidermal and dermal fractions. The activity in both fractions was markedly decreased following cholera toxin injection. The ability of cholera toxin to induce both epidermal and dermal ornithine decarboxylase activity developed between 10 and 21 days after birth. PMID- 6255036 TI - Protection against Japanese encephalitis virus in mice and hamsters by treatment with carboxymethylacridanone, a potent interferon inducer. AB - A low-molecular-weight chemical inducer of interferon, 10-carboxymethyl-9 acridanone (CMA), effectively prevented death caused by Japanese encephalitis virus (JEV) injected peripherally into weanling mice and baby hamsters. Marked reductions in mortality were seen in mice when a single dose of CMA was administered intraperitoneally, subcutaneously, or intramuscularly to animals challenged intraperitoneally with JEV. The degree of protection was dependent on dose and time of administration of CMA in relation to virus challenge: all hamsters given CMA on the same day as JEV survived, with lesser although still significant protection when CMA was given one or two days after JEV. Viremia, an important characteristic of the pathogenesis of natural JEV infection, was reduced nearly 10,000-fold in hamsters treated with CMA. Thus, in the experimental animal models developed for these studies, CMA provided marked therapeutic and prophylactic effect against JEV. PMID- 6255035 TI - Infection with herpes simplex virus and cell-mediated immunity after marrow transplant. AB - The relationship between herpes simplex virus (HSV) infection and specific cell mediated immunity was investigated in 141 patients before and for the first four months after marrow transplant. Sixty-two (82%) of 76 seropositive patients but only one of 65 seronegative patients developed HSV infection. Lymphocyte responses to HSV antigen were suppressed immediately after transplant and subsequently became reactive in those patients with HSV infection. The presence or absence of antibody to HSV in the donor before transplant did not influence the response. Seventy long-term survivors of marrow transplant were also studied. Among 60 patients who had pretransplant serum available for study, 26 (68%) of 38 who had been seropositive before transplant had positive responses compared with none of 22 who had been seronegative. Recovery of responsiveness to HSV antigen after marrow transplant is primarily related to recurrent virus infection and not to the pretransplant immune status of the donor. PMID- 6255037 TI - Transfusion-transmitted viruses study: experimental evidence for two non-A, non B, hepatitis agents. AB - Plasma, serum, and a concentrate of factor VIII, implicated in human cases of non A, non-B (NANB) hepatitis, were inoculated into four chimpanzees. All four animals demonstrated significant elevations of alanine aminotransferase levels within five weeks. After recovery from these NANB hepatitis episodes, the chimpanzees were cross-challenged with different inocula. A second episode of NANB hepatitis occurred after challenge in three animals. Reproducibility of the results was established by reversing the sequence of inoculation in two of the animals. A known infectious concentrate of factor VIII failed to induce hepatitis in a previously infected chimpanzee although the animal remained susceptible to a third inoculum, an event suggesting that the first inoculum might contain the same NANB hepatitis agent as the concentrate of factor VIII, which was supported by results of a subsequent cross-challenge experiment. Reinfection did not occur in two chimpanzees injected with their initial challenge strain of NANB hepatitis virus, providing evidence that strain-specific immunity had been established. Thus, experimental evidence is provided for the presence of two NANB hepatitis agents, supporting clinical and epidemiologic studies that favor the existence of more than one etiologic agent. PMID- 6255038 TI - Experimental infection of guinea pigs with varicella-zoster virus. AB - Weanling guinea pigs are susceptible to infection with varicella-zoster virus (VZV). Animals inoculated intranasally or subcutaneously with VZV grown in fetal guinea pig tissue culture shed virus from the nasopharynx and seroconverted to VZV. Viremia occurred in some animals. Animal-to-animal transmission of VZV was observed. Infection of weanling guinea pigs with VZV should allow assessment of the pathophysiology of viral infection in immunocompetent and specifically immunologically modified animals. PMID- 6255039 TI - Prevention of murine rotavirus infection with chicken egg yolk immunoglobulins. AB - Passive protection of infant mice against murine rotavirus was achieved with use of immunoglobulins from the eggs of chickens. Immunoglobulins were obtained by vaccinating hens with simian rotavirus, collecting the eggs after a high level of immunoglobulins was reached in the hen's serum, and isolating the water-soluble fraction from these eggs. The water-soluble fraction was then given twice daily to three-day-old mice to protect them from infection with murine rotavirus. The protection was found to decrease the infection rate from 90% to 15% with use of a standard dose of virus. PMID- 6255040 TI - Killing of virus-infected cells: the role of antiviral antibody and complement in limiting virus infection. PMID- 6255041 TI - NIAID News. Summary of the U.S.-Japan Hepatitis Panel Conference. PMID- 6255042 TI - Fluorometric assay for measurement of viral neuraminidase--application to the rapid detection of influenza virus in nasal wash specimens. AB - A sensitive assay was developed for the measurement of neuraminidase with use of the 4-methylumbelliferkyl-alph-ketoside of N-acetyl-neuraminic acid as a fluorescent substrate. Neuraminidase activity was detected in preparation containing small quantities of cultivated influenza virus as well as in some nasal wash specimens from human volunteers experimentally infected with influenza A/Alaska/78 virus. Activity due to influenza viral neuraminidase could be distinguished from activity due to bacterial or mammalian (fibroblast) neuraminidase by means of enzyme inhibition with ethylenediaminetetraacetate, a chelating agent. The same substrate could be used in a solid-phase assay to determine the antigenic type of the influenza viral neuraminidase. The fluorescent neuraminidase assay takes 2-4 hr to perform and uses equipment available in many laboratories. Thus, it offers promise for the rapid detection of influenza viruses in cell cultures and clinical specimens. PMID- 6255043 TI - Inactivated mouse cytomegalovirus vaccine: preparation, immunogenicity, and protective effect. AB - Mouse cytomegalovirus (CMV) was rapidly and completely inactivated at 37 C by formalin diluted 1:4,000. Of 18 mice that received two doses of inactivated mouse CMV, 16 survived challenge with 250% lethal doses of mouse CMV; one of 11 mice receiving two doses of a control preparation survived the challenge (P < 0.005). After challenge with live virus, recognizable morbidity occurred in only four of 16 recipients of inactivated mouse CMV, but the virus was recovered from the salivary glands of 15 animals. Mice with reciprocal prechallenge titers of neutralizing antibody of < 4 demonstrated significantly higher morbidity and mortality than mice with higher antibody titers. Administration of inactivated mouse CMV did not depress responsiveness of spleen cells to phytohemagglutinin. Most mice immunized with inactivated virus developed only mild or subclinical infections after challenge with lethal doses of mouse CMV. PMID- 6255044 TI - Simian virus 40-associated fatal interstitial pneumonia and renal tubular necrosis in a rhesus monkey. AB - Simian virus 40 was isolated from a young adult rhesus monkey dying of naturally acquired interstitial pneumonia and renal tubular necrosis. Light microscopic examination demonstrated basophilic intranuclear inclusions associated with the lesions in the lung and the kidney. These inclusions were positive for antigen of simian virus 40 by immunoperoxidase staining of paraffin sections of affected organs. Electron microscopy revealed characteristic papovarirus particles in these tissues. This study is the first report indicating that simian virus 40 may produce pulmonary and renal disease in its natural host. PMID- 6255045 TI - Antibodies to Aleutian disease virus in human sera. PMID- 6255046 TI - Recommendations of the study group for research and training in sexually transmitted diseases. PMID- 6255047 TI - Anterior parasternal mediastinotomy. PMID- 6255049 TI - The prevention of sensori neural deafness. AB - A review of the present position concerning the causes of congenital sensori neural deafness has been presented. Significant success has been achieved in the reduction, if not the elimination, of congenital deafness arising from the rhesus factor. Indications are that babies admitted to special care units show few children with severe sensori-neural deafness. The greatest opportunity for a significant reduction in the incidence of congenital sensori-neural deafness lies in the prevention of maternal infection by the rubella virus. There is a possibility that deafness could be avoided in many as one third of children so born if a vigorous vaccination programme is pursued. If the number of women undergoing abortion for suspected rubella continues at the same annual rate the reduction of children born deaf as a result of the rubella virus will anticipate the reduction which could be expected for an effective immunization programme. If the immunization programme can be fully implemented the need for abortion will decline. The relationship of prematurity and deafness is an area where doubt must still remain. Although some statistics have stressed the relationship between prematurity and congenital sensori-neural deafness, the latest study reported indicates that for the last four years prematurity has not featured as a significant concomitant factor. On the other hand, it does appear that, in the study of D'Souza, McCartney, Nolan and Taylor (1980) of the 26 babies who took ten minutes or more to establish spontaneous respiration, the one baby found to have a hearing loss was one of two babies who had no vital signs at birth. It may be that the establishment of a heart beat is even more significant than oxygen lack. Consideration of the value of offering genetic counselling to deaf school leavers is under consideration. PMID- 6255048 TI - Initiation and stages of mineralization in tympanosclerosis. AB - The ultrastructure of tympanosclerotic tissue is described with particular reference to the structure of matrix vesicles and calcospherules, often of intricate structure, and to their role in the induction of calcification. The vesicles formed by degenerating cells within the collagenous matrix or epithelium of the tympanosclerotic tissues are the primary site of calcification. The released spherules appear scattered throughout the collagenous layers, and form the organic basis of calcospherules. Through fusion larger aggregates are formed which lead to the development of macroscopically recognizable calcified plaques in the middle ear cleft. The entire process is triggered off by the inflammatory processes of otitis media. Compared with other processes of excessive fibrogenesis and calcification, tympanosclerosis fits well into the overall scheme of induced calcification in both normal and pathological conditions which is similar in all mineralizing tissues composed of collagen and protoglycons. The cause of the prolific fibrogenesis and mineralization has remained doubtful. Clearly inflammatory and degenerative processes in otitis media may trigger off the release of a factor (or factors), and of matrix vesicles acting as fibrogenetic stimulants and primary sites of calcification. Katchburian's working hypothesis of mineralization (Katchburian, 1973) has universal appeal and can be confirmed on the basis of our observations on tympanosclerosis. Tympanosclerosis may be added to the 'crystal deposition diseases' of McCarthy. PMID- 6255050 TI - Presence of herpes simplex virus type 2 (HSV-2) antibodies and antigens in patients with cervical carcinoma in Thailand. PMID- 6255051 TI - Renal tubular transport and nephrotoxicity of DDA. AB - Since DDA [bis(p-chlorophenyl)acetic acid] has been shown to be transported and concentrated by the renal proximal tubule, this metabolite of DDT has been postulated to be a potential nephrotoxic agent. The present study explored the renal transport of DDA in the isolated, perfused rat kidney and the effects of DDA on renal function. When DDA (0.6 microM) was present in a dextran perfusate which eliminated DDA-colloid binding, the DDA/inulin clearance ratio was congruent to 0.05; however, some metabolism of DDA was apparent. During these studies, DDA had no effect on the glomerular filtration rate and the fractional reabsorption of Na, K or H2O. To determine the concentration of DDA which would produce an effect on renal cellular function, studies were performed with renal cortical slices. DDA at media concentrations greater than or equal to 0.1 mM were needed to produce significant alterations in tetraethylammonium transport, tissue oxygen consumption and intracellular electrolyte composition; however, no effect was demonstrated on Na-K-ATPase activity although DDA did affect Mg-ATPase activity. In conclusion, DDA at a 0.6 microM perfusate concentration undergoes net tubular reabsorption and metabolism without affecting the function of the perfused kidney. Only high concentrations of DDA were shown to produce alterations in cellular function. PMID- 6255052 TI - The in vitro metabolism of 2,2',4,4',5,5'-hexabromobiphenyl. AB - Radiolabelled 2,2',4,4',5,5'-hexabromobiphenyl was metabolized in vitro by rat liver microsomal enzymes to give more polar ether soluble lipophilic metabolites, trichloroacetic acid soluble conjugates and a macromolecular adduct fraction. The rates of formation of the three metabolic fractions were significantly enhanced using Firemaster BP-6 and 2,2',4,4',5,5'-hexabromobiphenyl induced microsomal enzymes. Comparative metabolic studies with the 4-brombiphenyl substrate showed that the lower brominated biphenyl substrate was more readily metabolized and the rate of metabolism was enhanced only with the Firemaster BP-6 induced microsomal enzymes and not the 2,2', 4,4',5,5'-hexabromobiphenyl induced enzyme system. PMID- 6255053 TI - Protection from cancer by 'silica' in the water-supply of U.S. cities. PMID- 6255054 TI - The embryotoxic effects of cannabinoids in rats and mice. PMID- 6255056 TI - Assessment of the intake of dietary fibre from cereal foods: an epidemiological approach. AB - In a study evaluating the intake of dietary fibre from cereal foods the results obtained from a standard 7-day weighed record were compared with simpler methods. This showed that weighing was unnecessary to obtain a valid measure of intake. There was also a low ratio of within-subject to between-subject variation: thus four days of recording are all that are required. The 4-day unweighed record is cheaper, less complex, and may be expected to produce higher completion rates than the 7-day weighed record. PMID- 6255055 TI - Effects of asbestos and chemical carcinogens on the cyclic nucleotide system of human fibroblasts. PMID- 6255057 TI - A new spectrophotometric method for the determination of 5'-nucleotidase. AB - A spectrophotometric method is described for the determination of 5' nucleotidase. In combination with the enzymes nucleoside phosphorylase and xanthine oxidase, inosine, formed by hydrolysis of 5'-IMP by 5'-nucleotidase, is cleaved phosphorolytically to hypoxanthine, which is oxidized to uric acid. In the presence of ethanol, the hydrogen peroxide formed is reduced by catalase and equivalent amounts of acetaldehyde are produced. The aldehyde is dehydrogenated (NADP-dependent) by aldehyde dehydrogenase and the production rate of NADPH is recorded at 334 nm. The inhibition of the unspecific cleavage of 5'-IMP by phosphatases is examined critically. PMID- 6255058 TI - Primary aldosteronism. IV. Observations on the postural variation of plasma aldosterone concentration. PMID- 6255059 TI - Icteric type hepatoma. PMID- 6255060 TI - [Carcinoma of the rhinopharynx in France, and the Epstein-Barr virus. Presence of Epstein-Barr nuclear antigen in tumor tissue]. PMID- 6255061 TI - Thermodynamic and kinetic studies of the gating behavior of a K+-selective channel from the sarcoplasmic reticulum membrane. AB - A voltage-dependent, K+-selective ionic channel from sarcoplasmic reticulum of rabbit skeletal muscle has been studied in a planar phospholipid bilayer membrane. The purpose [corrected] of this work is to study the mechanism by which the channel undergoes transitions between its conducting and nonconducting states. Thermodynamic studies show that the "open" and "closed" states of the channel exist in a voltage-dependent equilibrium, and that the channel displays only a single open state; the channel conductance is 120 pmho in 0.1 M K+. The channel's gating process follows single exponential kinetics at all voltages tested, and the individual opening and closing rate constants are exponentially dependent on voltage. The individual rate constants may also be determined from a stochastic analysis of channel fluctuations among multiple conductance levels. Neither the thermodynamic nor the kinetic parameters of gating depend on the absolute concentration of channels in the bilayer. The results are taken as evidence that the channel gates by an unusually simple two-state conformational mechanism in which the equivalent of 1.1 net charges are moved across the membrane during the formation of the open channel. PMID- 6255062 TI - Ionic selectivity, saturation, and block in a K+-selective channel from sarcoplasmic reticulum. AB - The open-channel conductance properties of a voltage-gated channel from sarcoplasmic reticulum were studied in planar phospholipid membranes. The channel is ideally selective for K+ over Cl- and for K+ over Ca++. In symmetrical 1 M solutions, the single-channel conductance (in pmho) falls in the order: K+ (214) > NH4+ (157) > Rb+ (125) > Na+ (72) > La+ (8.1) > Cs+ (< 3). In neutral bilayers, the channel conductance saturates with ion activity according to a rectangular hyperbolic relation, with half-saturation activities of 54 mM for K+ and 34 mM for Na+. Under symmetrical salt conditions, the K+:Na+ channel conductance ratio increases with salt activity, but the permeability ratio, measured by single channel bi-ionic potentials, is constant between 20 mM and 2.5 M salt; the permeability ratio is equal to the conductance ratio in the limit of low-salt concentration. The channel conductance varies < 5% in the voltage range -100 to +70 mV. The maximum conductance varies K+ and Na+ is only weakly temperature dependent (delta H++ = 4.6 and 5.3 kcal/mol, respectively), but that of Li+ varies strongly with temperature (delta H++ = 13 kcal/mol). The channel's K+ conductance is blocked asymmetrically by Cs+, and this block is competitive with K+. The results are consistent with an Eyring-type barriers as it permeates the channel. The data conform to Luger's (1973. Biochem. Biophys. Acta. 311:423-441) predictions for a "pure" single-ion channel. PMID- 6255063 TI - Kinetics and thermodynamics of ouabain binding by intact turkey erythrocytes: effects of external sodium ion, potassium ion, and temperature. AB - The kinetics of association and dissociation for the ouabain-Na+,K+-dependent ATPase complex have been studied in intact turkey erythrocytes as a function of external Na+ concentration, K+ concentration, and temperature. At free ligand concentrations substantially exceeding the concentration of available binding sites, the association reaction exhibits pseudo-first-order kinetics with an association rate constant (k1) that is conveniently determined over a wide range of temperatures (5-37 degrees C). The dissociation reaction exhibits strict first order kinetics with a dissociation rate constant (k-1) that has the unusual property, in the turkey cell, of being sufficiently great to permit its direct determination even at temperatures as low as 5 degrees C. Values for the equilibrium binding constant for the ouabain-ATPase complex (KA) predicted from the ratio of the association and dissociation rate constants agree closely with independently measured values of KA determined directly under conditions of equilibrium binding. KA is a sensitive function of the composition of the external ionic environment, rising with increasing Na+ concentration and falling with increasing K+ concentration. These changes in KA are shown to be quantitatively attributable to changes in the rate constant k1, k-1 in contrast being unaffected at any given temperature by even very large changes in Na+ or K+ concentration. Arrhenius plots of k1 and k-1 both yield straight lines over the entire temperature range corresponding to activation energies for association and dissociation of 29.5 and 24.2 kcal/mol, respectively. These observations have made it possible to calculate the following standard values for the ouabain binding reaction in the presence of 150 mM Na+: delta G degree = -9.8 kcal/mol; delta H degree = +5.3 kcal/mol; delta S degree = +48.7 cal/degree/mol. The large positive value of delta S degree presumably reflects a highly ordered configuration of the ouabain-free ATPase molecule that is lost upon ouabain binding and that "drives" the reaction despite the positive value of delta H degree. PMID- 6255064 TI - Control of the cyclic GMP phosphodiesterase of frog photoreceptor membranes. AB - The light-activated cyclic GMP phosphodiesterase (PDE) of frog photoreceptor membranes has been assayed in isolated outer segments suspended in a low-calcium Ringer's solution. Activation occurs over a range of light intensity that also causes a decrease in the permeability, cyclic GMP levels, and GTP levels of isolated outer segments. At intermediate intensities, PDE activity assumes constant intermediate values determined by the rate of rhodopsin bleaching. Washing causes an increase in maximal enzyme activity. Increasing light intensity from darkness to a level bleaching 5 x 10(3) rhodopsin molecules per outer segment per second shifts the apparent Michaelis constant (Km) from 100 to 900 microM. Maximum enzyme velocity increases at least 10-fold. The component that normally regulates this light-induced increase in the Km of PDE is removed by the customary sucrose flotation procedures. The presence of 10(-3) M Ca++ increases the light sensitivity of PDE, and maximal activation is caused by illumination bleaching only 5 x 10(2) rhodopsin molecules per outer segment per second. Calcium acts by increasing enzyme velocity while having little influence on Km. The effect of calcium appears to require a labile component, sensitive to aging of the outer segment preparation. The decrease in the light sensitivity of PDE that can be observed upon lowering the calcium concentration may be related to the desensitization of the permeability change mechanism that occurs during light adaptation of rod photoreceptors. PMID- 6255065 TI - The gene-enzyme relationships of proline biosynthesis in Escherichia coli. AB - A simple chromatographic procedure has been devised to separate gamma-glutamyl phosphate reductase and 1-pyrroline-5-carboxylate reductase, allowing the measurement of the former in crude Escherichia coli extracts. Analysis of a number of strains of E. coli has demonstrated that gene proA codes for gamma glutamyl phosphate reductase and proB for gamma-glutamyl kinase. Introduction of a ColE1 hybrid plasmid containing the proA,B region into a strain with a chromosomal deletion of proA,B led to 3- and 17-fold increases in the specific activities of gamma-glutamyl kinase and gamma-glutamyl phosphate reductase, respectively. PMID- 6255066 TI - Mapping of the thymidine kinase genes of type 1 and type 2 herpes simplex viruses using intertypic recombinants. AB - The thymidine kinase induced in lytic infection by each of 36 intertypic recombinants of herpes simplex virus (HSV) type 1 and type 2 was identified as type 1 or type 2 by studies on the thermolability of enzyme activity, neutralization with type 1 or type 2 antiserum and agar gel immunodiffusion with type 1 or type 2 thymidine kinase antiserum. Fourteen recombinants induced no thymidine kinase, 12 induced type 1 thymidine kinase and 10 induced type 2 thymidine kinase. Correlation of these results with restriction endonuclease analysis of the DNA of the recombinants with five restriction endonucleases (XbaI, EcoRI, HpaI, HsuI, and Bg/II) allowed mapping of the type 1 thymidine kinase gene at 0.300 to 0.309 map unit and the type 2 thymidine kinase gene at 0.295 to 0.315 map unit. PMID- 6255067 TI - DNA binding and unwinding activities associated with intracytoplasmic a particles isolated from mouse mammary tumors. AB - Intracytoplasmic A particles (CAP), previously identified as probably cytoplasmic nucleocapsid precursor structures to mouse mammary tumour virus (MMTV), possess both DNA binding and DNA unwinding activities, CAP proteins bind to both single stranded (ss)- and double-stranded (ds)DNA, with the ssDNA slightly preferred. This activity was linear over a 30-fold concentration of A particle protein and was not affected by NaCl concentrations as high as 0.6 M or pH changes over a wide range. DNA binding by CAP proteins was sensitive to heat or addition of sodium dodecyl sulphate (SDS) and was neutralized by pre-incubation of CAP with anti-MMTV p14, but not by anti-MMTV p27, p10 or anti-mouse casein. Incubation of CAP with dsDNA led to unwinding of the double helix as measured by its increased sensitivity to S1 nuclease digestion. This activity was also linear over a several-fold concentration of A particle protein and was heat labile. It was not inhibited by pre-incubation of CAP with either anti-MMTV p14 or with anti-MMTV, anti-MMTV p27 and anti-MMTV p10. DNA unwinding was inhibited by anti-A particle antiserum and to a lesser extent by anti-CAP p20-18. PMID- 6255068 TI - Characterization of the non-permissive infection of rabbit cornea cells by vesicular stomatitis virus. AB - Rabbit cornea cells (RC-60) restrict the reproduction of vesicular stomatitis virus (VSV) (Thacore & Youngner, 1975). In cells infected with VSV alone, an inhibition in the synthesis of VSV genome RNA is observed. A number of parameters which could affect virus RNA synthesis have been examined: virus transcription and post-transcriptional modification, translation, modification of proteins and migration of the G protein to the surface of the cell; they all appear to be normal, although somewhat diminished, in the restricted system. In these cells, therefore, it is the replication of VSV RNA that is directly inhibited, although limited synthesis of both (+) and (-) strand genome length RNA does occur. When the cells are co-infected with rabbit poxvirus (RPV) as a helper virus, however, VSV production is normal. Our studies suggest that RPV plays a role in the maturation as well as in the replication of VSV RNA in RC-60 cells. Certain mutants of RPV have been found to lack the helper function and are unable to convert the RC-60 cells into a permissive host for VSV. These mutants should facilitate the elucidation of the mechanism by which RPV is able to overcome the restriction in these cells. PMID- 6255070 TI - Cell-mediated immunity in herpes simplex virus-infected mice: functional analysis of lymph node cells during periods of acute and latent infection, with reference to cytotoxic and memory cells. AB - The functional characteristics of lymphoid cells were investigated during acute and latent infection of mice with herpes simplex virus (HSV). Cytotoxic T cells were found in the draining lymph node (DLN) 4 days p.i. and had reached maximum activity between 6 and 9 days. After the 12th day and during the period of latent infection (> 20 days) no cytotoxic cell activity was observed. Cytotoxic activity could only be detected when the lymphoid cells had been cultured for a period of 3 days. In general, the cell killing was specific for syngeneic infected target cells, although some killing of uninfected targets was observed. In contrast to the cytotoxic response, DLN cells responding to HSV in a proliferation assay were detected towards the end of the acute phase and at lease up to 9 months thereafter. The significance of these observations for the pathogenesis of HSV is discussed. PMID- 6255069 TI - Growth and release of several alphaviruses in chick and BHK cells. AB - The growth and release of several alphaviruses, including several strains of Sindbis virus (the wild-type strain, the large plaque and small plaque variants of the HR strain, and the HR mutant ts103), Semliki Forest virus(SFV) and Middelburg virus, and of the unrelated rhabdovirus, vesicular stomatitis virus (VSV), have been compared in chick cells and in BHK-21 cells as a function of the culture conditions for the host cell and the ionic strength of the medium. The small plaque strain of Sindbis HR, as well as SFV, grew better in BHK cells, whereas the large plaque strain of Sindbis HR showed a preference for chick cells. Wild-type Sindbis and VSV grew equally well in either cell. The optimum ionic strength for virus production as well as inhibition of virus release into the medium at low ionic strength depended upon both the virus and the host cell. Thus, VSV grown in medium of low ionic strength gave no additional release of virus on incubation with hypertonic medium (minimum effect), whereas ts103 released very little virus without exposure to hypertonic conditions (maximum effect). The viruses could be ordered as follows: minimum effect = vesicular stomatitis virus < Middelburg virus < Semliki Forest virus < Sindbis wt < Sindbis HR (large plaque) < Sindbis HR (small plaque) < Sindbis ts103 = maximum effect. After several passages in culture, chick cells required hypertonic conditions for optimum production and release of Sindbis virus. Furthermore, BHK cells cultured in different media responded differently to ionic strength for virus production and release. These results suggest that there is a charge-dependent stop in the maturation of alpha-viruses, possibly a configurational rearrangement of glycoprotein E2 upon its formation from the precursor PE2, which is sensitive to the ionic strength of the medium, to the composition of the host plasmalemma and to differences in the virus glycoproteins. PMID- 6255071 TI - The characteristics of the cell-free translation of mRNA from cells infected with the herpes virus pseudorabies virus. AB - The translation in vitro of mRNA from pseudorabies virus infected cells was studied using systems derived from wheat germ and from rabbit reticulocyte. The mRNA was shown by molecular hybridization to contain sequences complementary to virus DNA. Products of in vitro translation co-migrating with virus proteins on polyacrylamide gel electropherograms were detected and the major immune precipitation. Optimum conditions for the stimulation of amino acid incorporation in vitro were determined and found to be similar for mRNA from both infected and mock-infected cells. PMID- 6255072 TI - A non-virion surface antigen on Moloney sarcoma virus-transformed non-producer and producer cells. AB - Sera from STU mice bearing sarcomas induced by cells producing the Moloney sarcoma-helper-virus (M-MSV/MLV) complex were cytotoxic for these cells as well as for M-MSV non-producer and M-MLV producer cells. Analysis by polyacrylamide gel electrophoresis of 125I-labelled surface antigens immunoprecipitated with such sera revealed the virus envelope glycoprotein gp71 on the producer cells and an additional antigen of mol. wt 55 K on the M-MSV-transformed producer and non producer cells. This antigen was not found on non-transformed M-MLV-producing cells and was neither related serologically to structural polypeptides of murine C-type viruses nor to components of embryonal STU mouse fibroblasts and foetal bovine serum. PMID- 6255073 TI - The effect of polyamines on herpes simplex virus type 1 DNA polymerase purified from infected baby hamster kidney cells (BHK-21/C13). AB - The DNA polymerase whose synthesis is directed by the herpes simplex virus type 1 (HSV-1) DNA was purified 545-fold from BHK-21/C13 cells 16 h after infection with the virus. Spermidine and spermine stimulated the activity of the polymerase over the concentration range 0.5 mM to 2.5 mM. This effect was enhanced with increased concentrations of polyamine, maximum stimulation being threefold and fourfold for spermidine and spermine respectively. The diamine, putrescine, had little effect on the enzyme at the concentrations used (0.25 to 1.25 mM). PMID- 6255074 TI - Effect of immune serum on the establishment of herpes simplex virus infection in trigeminal ganglia of hairless mice. AB - Administration of immune serum to herpes simplex virus (HSV)-infected hairless mice could not prevent acute infection in the trigeminal ganglia and the eventual establishment of latency. However, immune serum reduced the amount of free virus in the ganglion during the acute phase of the infection. It appears also that the amount of virus that can be reactivated in the latently infected ganglion is decreased. This was indicated by a prolonged reactivation time and by a reduced virus content of ganglion homogenates prepared after various periods of cocultivation. PMID- 6255075 TI - Characterization of X-tropic endogenous retrovirus-specific RNA uninfected tissues and lymphosarcoma of BALB/c mice. AB - Analysis of endogenous X-tropic BALB/c retrovirus-specific RNAs in a BALB/c mouse tissue containing mostly non-driving cells (liver), in two normal tissues having significant proportions of dividing cells (20-h regenerating liver and 12-day embryo) and in cells of a lymphosarcoma of BALB/c mice were carried out by determining the extent to which the RNAs from these tissues hybridized to the virus 3H-cDNA probe and by their relative sedimentation values in a sucrose gradient. RNAs from 20-h regenerating liver, 12-day embryo and lymphosarcoma, each containing a significant proportion of proliferating cells, showed 8 to 21 % higher hybridization values than normal liver RNA. Differences in the exact size classes of virus-specific RNAs and, in their relative proportions were found to exist in the four different tissue types examined and no correlation between a specific RNA size-profile and the proliferating activity of a tissue could be detected. PMID- 6255076 TI - Structural heterogeneity in p30 molecules of type C viruses. AB - Tryptic digests of p30 proteins from mouse type C viruses were subjected to cation-exchange chromatography. Structural heterogeneity of p30 molecules was seen in two specific areas of the peptide elution profiles. These hypervariable regions of p30 proteins were used to discriminate representative ecotropic (N- and B-tropic), xenotropic (alpha and beta) and amphotropic viruses. PMID- 6255077 TI - The effect of delta-9-tetrahydrocannabinol on herpes simplex virus replication. AB - Both herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) failed, in an identical fashion to replicate and produce extensive c.p.e. in human cell monolayer cultures which were exposed (8 h before infection, at infection, or 8 h p.i.) to various concentrations of delta-9 tetrahydrocannabinol. Similar results were obtained with a plaque assay utilizing confluent monkey cells. Possible mechanisms for this antiviral activity are discussed. PMID- 6255078 TI - A comparative study on the u.v. resistance of double-stranded and single-stranded encephalomyocarditis virus RNAs: evaluation of the possible contribution of host mediated repair. AB - To reveal previously suggested host-mediated repair of u.v.-induced lesions in dsRNA of encephalomyocarditis (EMC) virus, two sets of experiments have been carried out: (i) samples of dsRNA of EMC virus were irradiated with different doses of u.v. light and their infectivity was assayed in krebs II cells, before and after conversion of dsRNA into a ss form: (ii) samples of ssRNA of EMS virus were similarly irradiated and their infectivity was assayed before and after conversion of ssRNA into a ds form. No evidence for a significant host-mediated repair of dsRNA in this virus-cell system has been obtained. PMID- 6255080 TI - The budding mechanisms of enveloped animal viruses. PMID- 6255079 TI - Simian virus 40 and Moloney-murine sarcoma virus infection of bona fide mouse epithelium. AB - Moloney-murine sarcoma virus (Moloney-MSV) and simian virus 40 (SV40) were found to infect successfully pure cultures of epithelial cells established from mouse liver and mammary tissue. MSV infection resulted in transient morphological foci with persistent production of infectious virus. SV40 infection produced detectable levels of virus-specific T antigen in the cells but morphological transformants were not observed. PMID- 6255082 TI - Studies on recombination in heterologous crosses of Rous sarcoma virus. AB - Ts mutants in src from the Prague and Schmidt-Ruppin strains of Rous sarcoma virus (RSV) were used to superinfect chicken and quail cells chronically infected with the Bryan strain of RSV. No wild-type recombinants and few double-defective virions were produced. These results indicate that genetic recombination does not occur with high frequency in these heterologous crosses even if all infectious virus is derived from doubly infected cells. PMID- 6255081 TI - Quantification of plasminogen activator activity associated with herpesvirus transformed cells. AB - Herpesvirus-transformed cell lines were examined for plasminogen activator (PA) activity using a quantitative assay. Previous results of cold fibrin overlay assays indicated that herpesvirus-transformed hamster cell lines produce fibrinolytic activity. Quantification of this activity involved the use of an 125I-fibrin lysis assay in which medium previously incubated with transformed or normal cells was tested for its ability to lyse 125I-fibrin polymers. This assay indicated an enhanced production of plasminogen-dependent fibrinolytic activity by transformed hamster cells compared to hamster embryo fibroblasts. The kinetics of secretion failed to reveal a significant difference in plasminogen activator activity in cells transformed by either herpes simplex virus types 1 or 2 (HSV-1 or HSV-2); however, transformed cells exhibited a significant increase in activity over non-transformed cells. Further characterization of PA activity associated with cells transformed by HSV-1 or HSV-2 has revealed that the protease is secreted and can function extracellularly. Extracellular PA activity produced by HSV-transformed cells is detected more efficiently than the cell associated enzyme. Extracellular PA can be induced in two different species of cells by infection with partially inactivated HSV-2. Lytic infection of human embryo lung cells by HSV-2 strain 333 did not enhance activity, but infection of these cells with virus inactivated by u.v. irradiation resulted in increased PA levels from the cells. Increased enzyme levels were also detected in hamster embryo fibroblasts infected with partially inactivated virus. Further investigation of this enzyme function may determine whether increased levels of protease will indicate oncogenic transformation in vitro by herpesviruses. PMID- 6255083 TI - Biological properties of polyoma DNA fragments cloned in plasmid pBR322. AB - The two HindIII fragments of polyoma virus DNA were cloned in the HindIII site of plasmid pBR322, and the biological activity of the recombinant plasmids was tested in tissue culture cells. A mixture of recombinant plasmids containing the HindIII-A and HindIII-B fragments was infectious, but only after cleavage with HindIII. Recombinant plasmids containing the HindIII-A fragment, but not those containing the HindIII-B fragment, induced the transformation of Fischer rat 3T3 cells. These findings indicate that about half of the early region of polyoma virus DNA is not essential for the initiation of the maintenance of transformation. PMID- 6255084 TI - Plaque formation and purification of BK virus in cultured human urinary cells. AB - Primary human urinary cells support growth and plaque formation by papovavirus BK, permitting plaque purification of the virus. After plaquing, the virus forms uniform plaques and its DNA has a homogeneous restriction enzyme fragment profile. Support of BK replication as well as morphological and cultural characteristics suggest an epithelial origin for the cells. PMID- 6255085 TI - Investigation of immunoperoxidase-labelled rotavirus in tissue culture by light and electron microscopy. AB - A tissue culture-adapted strain of bovine rotavirus, grown in calf kidney monolayers, has been examined by light and electron microscopy after immunoperoxidase labelling. Some of the characteristic problems associated with pre-embedding methods have been demonstrated. Preparative techniques involving pretreatment of infected cells with a detergent followed by a detergent/fixative combination have enabled virus antigen to be labelled while maintaining satisfactory ultrastructural preservation. PMID- 6255086 TI - Simultaneous injection of newborn rabbits with the Schmidt-Ruppin and prague strains of Rous sarcoma virus induces antibodies which recognize the pp60src of both strains. AB - Simultaneous injection of newborn rabbits with the Schmidt-Ruppin and Prague strains of Rous sarcoma virus regularly induces antibodies which not only recognize the pp60src of both strains but also give positive kinase reaction with extracts of cells infected with either strain. PMID- 6255087 TI - Detection of IgM antibodies to cytomegalovirus (CMV) using an enzyme-labelled antigen (ELA). AB - We have applied a peroxidase enzyme-labelled antigen (ELA) for the detection of IgM antibodies to cytomegalovirus: microtitre plates were coated with anti-IgM immunoglobulin. The IgM fraction of human serum was selectively bound to the precoated plates and the virus-specific IgM antibody was then detected by the enzyme-labelled antigen. A very efficient technique for the labelling of virus antigen is described. The IgM antibody was detected simply and specifically, Rheumatoid factor IgM did not interfere with this test. PMID- 6255088 TI - Biological characterization of the virus causing leukoencephalitis and arthritis in goats. AB - This study describes the biological properties of a strain of virus isolated from tissues of a goat with leukoencephalomyelitis-arthritis. The agent is a retrovirus, having a virion-associated reverse transcriptase enzyme and an antigenic determinant(s) which cross-reacts with the p30 of visna-maedi viruses. Morphogenesis of the virus is also similar to visna virus in terms of virus assembly and the multinucleated giant cell formation which accompanies replication of the latter virus. Despite its cytopathogenic property the goat agent was not lytic in goat cell culture, causing instead a productive infection which persisted through multiple subcultures of the cells. The virus replicated incompletely in sheep cell cultures but could be rescued from the latter, weeks after inoculation, by co-cultivation with goat cells. Our data suggest that this strain of goat leukoencephalitis virus is a variant of the ovine retroviruses with a host range limited to the goat. PMID- 6255089 TI - Delta-9-THC in pigeons: a replication and extension. PMID- 6255090 TI - Presurgical adjustment in male transsexuals with and without hormonal treatment. AB - The effects on hormonal treatment on the adjustment of adult males requesting sex reassignment surgery were examined in two studies. In study 1, the Minnesota Multiphasic Personality Inventory (MMPI) profiles of 19 patients who received no hormonal therapy and 22 patients who received 12 or more months of estrogen and medroxyprogesterone acetate treatment were compared. Patients receiving hormonal therapy not only showed significantly less psychopathology, but their scores on MMPI scales indicating neurotic and study 2, using correlational techniques to assess the effects of both hormonal treatment and cross-dressing on psychopathology. Length of hormonal treatment was related to emotional adjustment on four clinical scales of the MMPI. Scores indicating greater adjustment were associated with longer periods of treatment. Length of full-time cross-dressing, on the other hand, was not associated with patients' level of adjustment. These findings have important implications for those involved in personality evaluation of transsexuals and for future research. A more rigorous criteria for psychopathology may be required for those persons already exposed to hormonal therapy. It if further suggested that personality research with presurgical transsexuals include a drug hormone history. PMID- 6255091 TI - Connectivity changes in an isolated molluscan ganglion during in vivo culture. AB - The stability of neuronal connections in the isolated buccal ganglia of Helisoma trivolvis was examined during in vivo culture for periods up to one month. After 4--8 days the characteristic IPSP input to protractor motoneurons (PMNs) was either abolished or reduced in efficacy. This is apparently due to reduced efficacy of chemical synapses, since the input resistance and resting potential of the motoneurons is unchanged and a fraction of spike-evoked IPSPs from premotor neurons (cyberchrons) onto PMNs was absent. PMNs lacking IPSP input nevertheless exhibit vigorous cyclical bursts of action potentials driven by electrical EPSPs. The IPSP of PMNs showed partial or full restoration after 14- 32 days of culture despite the lack of reinnervation of normal targets. Existing electrical synapses were apparently more stable during culture, but electrical connections between cyberchrons and PMNs were strengthened. Probably because of the reinforcement of these electrical synapses, regenerative cycles of activity in both cyberchrons and PMNs may often be initiated by brief stimulating of a single PMN in cultured ganglia. This is in marked contrast to normal ganglia in which PMNs possess a limited ability to generate such activity. It is concluded that isolation of the buccal ganglia results in a predictable, functional alteration of its neuronal circuitry. Such a perturbation of connectivity indicates that a significant degree of plasticity can be exhibited by adult molluscan neurons. PMID- 6255092 TI - Stimulation is necessary for the development of tolerance to a neuronal effect of ethanol. AB - Ethanol accelerates the decay of post-tetanic potentiation at an identified synapse in Aplysia. We have previously shown that with repeated exposures the ethanol effect diminishes, a development termed "tolerance." Here we present evidence that the establishment of tolerance depends on a adequate stimulation of the presynaptic terminal in the presence of ethanol. Elevated magnesium in the perfusion medium prevents tolerance, whereas elevated calcium in the perfusion medium reduces the amount of stimulation required for tolerance to develop. PMID- 6255093 TI - Interaction of Pd(II) glycyl--L-histidine complex with cytidine and GMP. Proton and carbon-13 nmr studies. AB - 1H and 13C nmr studies on the Pd(II)Gly-His complex interaction with cytidine and GMP have shown that the nucleoside binds the palladium complex via N3 nitrogen and the nucleotide binds that complex via N7 nitrogen. The analysis of the Cyd or GMP aromatic ring influence on the chemical shift of the H2 proton or the C2 carbon of imidazole ring has supported the earlier suggestions that nucleoside or nucleotide base and Pd(II) complex plane are almost perpendicular to each other. The Pd(II)Gly-His: Cyd or GMP ternary systems are easily decomposed already in weak basic solutions, which may suggest that the polymerization of Pd(II)Gly-His binary species might be the competitive process in the interactions with nucleosides or nucleotides. PMID- 6255094 TI - Effect of Mg2+ and Mn2+ on hydrolysis of calf thymus DNA by pancreatic deoxyribonuclease I. AB - Divalent cations are activators for DNA hydrolysis by pancreatic deoxyribonuclease I. Apparent Vm and Km changes have been studied in presence of Mn2+ or Mg2+. The activation process modifies both Vm and Km, their relationship with Mg2+ or Mn2+ being a linear one. Deoxyribonucleotides inhibit the DNA hydrolysis, whether Mg2+ or Mn2+ is the activator; the purine deoxyribonucleotides are more effective as inhibitors than the pyrimidine ones. The effect of some derivatives of adenine has been studied: the inhibition is maximum with 5'-dAMP and minimum with adenine or adenosine. A kinetic mechanism of enzymatic activation by Mn2+ or Mg2+ is discussed. PMID- 6255095 TI - Conductimetric study of the binding of Mn2+ to bovine pancreatic deoxyribonuclease. AB - The binding of Mn2+ on bovine pancreatic deoxyribonuclease has been studied by a conductimetric method. At low ionic strengths, a high-affinity single binding site is demonstrated. The association constant value (K = 1.2 x 10(5) M-1 at pH 8) is high enough to conclude that, in standard experimental conditions for DNA hydrolysis, the reacting species is the DNAase-cation complex. Competitive binding studies in presence of Mg++ and Ca++ show that these cations do not bind on the Mn++ site. PMID- 6255096 TI - Thiamine and cholinergic transmission in the electric organ of Torpedo. I. Cellular localization and functional changes of thiamine and thiamine phosphate esters. AB - The electric organ of Torpedo marmorata was found to contain as much as 120 +/- 24 nmol of thiamine per g of fresh tissue. The vitamin was distributed as nonesterified thiamine (32%), thiamine monophosphate (22%), thiamine diphosphate (8%), and an important proportion of thiamine triphosphate (38%). A high level of thiamine triphosphate was found in synaptosomes isolated from the electric organ. In contrast, the synaptic vesicles did not show any enrichment in thiamine, whereas they contained a marked peak of acetylcholine (ACh) and ATP. Thus thiamine seems to be very abundant in cholinergic nerve terminals; its localization is apparently extravesicular, either in the axoplasm or in association with plasma membrane. When calcium was reduced and magnesium increased in the external medium, the efficiency of transmission was diminished, owing to inhibition of ACh release; in a parallel manner the degree of thiamine phosphorylation was found to increase--this condition is known to modify the repartition of ACh between vesicular and extravesicular compartments. Electrical stimulation, which causes periodic variations of the level of ACh and ATP, also caused significant changes in thiamine esters. In addition, related changes of the vitamin and the transmitter were observed under other conditions, suggesting a functional link between the metabolism of thiamine and that of ACh in cholinergic nerve terminals. PMID- 6255097 TI - Cerebellar hypoplasia in the Gunn rat with hereditary hyperbilirubinemia: immunohistochemical and neurochemical studies. AB - Immunohistochemical reactions were conducted, using the antibodies against GFA and S-100 proteins on sections of cerebellum from the homozygous (jj) and the heterozygous (Jj) Gunn rats. Hypertrophy of the fibrous astrocytes was observed but hyperplasia of the glial cells was not. Although the molecular layer was very thin, the Bergmann fibre appeared normal. Among the free amino acids in the cerebellum from the jj rat, glutamate concentration decreased to two-thirds of the control level. The protein profile of the cerebellum from the jj rat obtained by SDS-polyacrylamide gel electrophoresis revealed that the amount of P400 protein that is characteristic of Purkinje cells decreased considerably and there were also some changes of the other unidentified proteins. By two-dimensional electrophoresis, it was observed that in the supernatant from the jj rat cerebellum one protein spot diminished and in the particulate fraction from the jj rat one spot was enormously increased. The activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase) in the cerebellum from the jj rat did not differ significantly from that of the control; however, activities of choline acetyltransferase and acetylcholinesterase of the jj rat were about twice as high as those of the control. 2-Deoxyglucose incorporation was maximum in the granular layer from both the jj and the Jj rat cerebella. However, the incorporation in the jj cerebellum was not higher than in the Jj control and even lower in some parts of the jj cerebellum than in the control Jj cerebellum. PMID- 6255098 TI - Cyclic AMP enhancement of depolarization-induced NAD(P)H changes in brain cortical slices. AB - The increased levels of NAD(P)H effected by electrical depolarization are markedly augmented in the presence of cyclic AMP, isoproterenol, or RO 20-1724, agents known to elevate cyclic AMP in rat brain slices. The data presented indicate that the cyclic AMP effect on an important component of intermediate metabolism is not an enhancement of a basal response but a separate response that is activated by depolarization, is Ca2+-dependent, regulates cytochrome a-a3 independently of its effects on NAD(P)H levels, and is dependent on a substrate other than glucose. PMID- 6255099 TI - Evidence for the association of 2',3'-cyclic-nucleotide 3'-phosphodiesterase with myelin-related membranes in peripheral nervous system. AB - In PNS, the specific activity of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) in myelin was not enriched over the starting homogenate. Nevertheless, most of the total activity was recovered in myelin. In myelin-deficient mutants, low CNP activities were measured in sciatic nerves. CNP specific activities were similar in myelinated and non-myelinated nerves but in non-nervous tissues, they were significantly lower than in nervous tissue. There was no indication for the presence of an isoenzyme of CNP in peripheral nerves. These results indicate that CNP is present in PNS myelin and preferentially localized in Schwann cell plasma membranes. PMID- 6255100 TI - Effects of denervation and simple disuse on rates of oxidation and on activities of four mitochondrial enzymes in type I muscle. AB - To differentiate the effect of muscle contractile activity from that of motor nerve on oxidative processes in type I muscle, oxidative processes were studied in muscle after immobilization and after denervation. The two processes led to similar atrophy of muscle weight and of the mean diameter of muscle fibers. Disuse of soleus muscle (type I) did not affect rates of oxidation of 14C-labeled substrates although these were reduced by disuse of the vastus lateralis (type II). Disuse of the soleus did not affect activities of several mitochondrial enzymes assayed by histochemical or biochemical methods. However, denervation of the soleus did lead to a fall in metabolic rates and enzyme activities. The activity of 3-hydroxybutyrate dehydrogenase fell more than did the activities of succinic dehydrogenase, lipoamide dehydrogenase, or cytochrome-c oxidase in both homogenates and in mitochondrial fractions. These results suggest nerve may regulate mitochondrial enzymes in type I muscle. The mechanism appears to be different from that which regulates oxidative processes in type II muscle. PMID- 6255101 TI - Decreased benzodiazepine receptor density in rat cerebellum following neurotoxic doses of phenytoin. AB - The effect of acute and chronic administration of phenytoin on [3H]flunitrazepam binding was examined in the rat cerebellum. There was no significant effect of phenytoin on [3H]flunitrazepam binding in the rat cerebellum 1 and 6 h after a single i.p. injection of 200 mg/kg of phenytoin. However, after 14 days and 28 days of chronic phenytoin administration, significant decreases in [3H]flunitrazepam receptor density were observed, with no changes in apparent affinity constants in the rat cerebellum. This effect of phenytoin was dose dependent, as lower doses of phenytoin (100 mg/kg/day) for 14 or 28 days produced no alterations in [3H]flunitrazepam binding the the rat cerebellum. Light microscopic examination of the rat cerebellum treated with 200 mg/kg/day of phenytoin for 14 days showed degeneration of the Purkinje cells, with edematous Bergmann astrocytes. These data provide evidence for the neuronal localization of benzodiazepine receptors on cerebellar Purkinje cells. PMID- 6255103 TI - Motor unit potential abnormalities in multiple sclerosis: further evidence for a peripheral nervous system defect. AB - We have recently reported abnormalities of single fibre EMG in patients with multiple sclerosis. The present study applies quantitative electrophysiological techniques to the same group of patients. The number of motor units in the extensor digitorum brevis muscle was measured and their characteristics recorded. Also the shortest distal motor latency and fastest motor conduction velocities were estimated. Abnormalities suggesting a patchy denervating/reinnervating process due to pathology in the intramuscular nerve network or at the endplate were found in a number of patients. There was a good correlation between patients with abnormal motor unit potentials and those with abnormal single fibre EMG "jitter". PMID- 6255102 TI - Eaton-Lambert syndrome: a clinical and electrophysiological study of a patient treated with 4-aminopyridine. AB - In a patient with the Eaton-Lambert syndrome, 4-aminopyridine produced temporary improvement of clinical and electromyographic abnormalities. Application of the drug in vitro to intercostal muscle from the patient produced an increase in the evoked release of neurotransmitter from intramuscular nerves. PMID- 6255104 TI - The role of folate deficiency in the development of peripheral neuropathy caused by anticonvulsants. AB - To investigate the role of folate deficiency in neuropathy caused by anticonvulsants, electrophysiological studies of peripheral nerve function were carried out on 29 epileptic patients on long-term anticonvulsant therapy. All but three patients showed abnormalities in one or more electrophysiological measurements, the main abnormality being in amplitude of sensory nerve action potential--this was reduced or absent in 76% of patients. All patients had low concentrations of folate in serum and CSF, these being below the normal ranges in 19 patients. These 19 patients were treated with folate, either 5 formyltetrahydrofolate (10 patients) or folic acid (9 patients), over a period of one month. After therapy all patients had normal levels of folate in serum and CSF, slightly higher levels in CSF being obtained in those receiving 5 formyltetrahydrofolate. Folate therapy significantly reversed abnormalities in motor and sensory nerve distal latencies; the effect was greater with 5 formyltetrahydrofolate, apparently because this produced higher CSF folate concentrations than folic acid. We conclude that folate deficiency may be involved in the development of peripheral neuropathy due to anticonvulsants. PMID- 6255105 TI - Quantitative electromyography using automatic analysis--diagnostic utility of turns per unit amplitude. AB - Quantitative electromyographic (QEMG) data from 3 muscles recorded with a 50 micronV threshold for the turns and amplitude measurements are presented. Using turns per unit amplitude as the index, consistent and comparable readings were recorded from abductor digiti minimi, biceps brachii and vastus medialis in normal subjects, namely 1.132 +/- 0.08 (31 subjects), 1.059 +/- 0.122 (31 subjects) and 1.007 +/- 0.088 (11 subjects), respectively. It is shown here that the diagnostic yield increases when all 3 values, namely, turns/s, average amplitude and turns/unit amplitude are considered in conjunction rather than considering the first 2 alone. PMID- 6255106 TI - Analysis of peripheral nerve function in streptozotocin diabetic rats. AB - Conduction velocity of rat sciatic nerve, estimated both in vivo and in vitro, did not change during 2--21 weeks following induction of diabetes by injection of streptozotocin. During this period blood sugars were in the range 17.6--30.4 mM and symptoms of uncontrolled diabetes were noted. The failure of velocity to decrease contrasts strongly with several previous reports, while the failure to increase with age may be explained with the aid of published morphometric data. Experiments on nerve fibers isolated from streptozotocin-diabetic rats rats confirmed that the nerve function was normal in respect of action and resting potential. Potential clamp analysis of nodal membrane similarly indicated that these fibres had normal permeability properties. PMID- 6255107 TI - Serotonin induces a voltage-sensitive calcium current in neurons of Aplysia californica. PMID- 6255108 TI - Developmental modulation of an identified electrical synapse: functional uncoupling. PMID- 6255109 TI - Physiological basis of feeding behavior in Tritonia diomedea. II. Neuronal mechanisms. AB - 1. The nudibranch mollusk Tritonia diomedea feeds by biting and drawing pieces of coelenterate sea whips into its buccal cavity. It then swallows them in a series of cyclic ingestion movements. The coordinated pattern of swallowing can be elicited in reduced preparations by stimulation of identifiable neurons in cerebral or buccal ganglia. 2. Swallowing normally proceeds as a cyclic pattern of protraction and retraction movements driven by alternating bursts in odontophore-radula protractor and retractor motor neurons (MNs), with simultaneous coordination of many other major neurons. 3. Brief or prolonged constant-current stimulation of certain individual buccal ganglion (SW) premotor neurons reliably triggers one or more complete cycles of impulse bursts in motor neurons with coordinated movements of the jaws and buccal mass. The MN bursts produced in this way resemble the ones seen during feeding. Some SW neurons trigger responses that greatly exceed the duration of the stimulus; others drive cyclic output in the motor system whose duration corresponds closely to the duration of the depolarizing current. As well, the rate of MN bursting can be modulated by steady currents of different amplitudes injected into these SW neurons. There are, however, alternative sensory and motor routes independent of SW neurons by which the motor pattern may be elicited and modulated. 4. A search for the source of the feeding rhythm resulted in the identification of a pair of motor neurons (B5) that have prominent burst and pattern-generating capabilities independent of SW activation. They fire vigorous impulse bursts on rebound from spontaneously occurring IPSP waves or from imposed hyperpolarizing potentials of similar amplitude and duration. 5. Constant prolonged depolarizing currents injected into B5 result in the production of repetitive bursts in other MNs that resemble in amplitude and time course those seen during feeding. Cyclic bursting generated in this way apparently entrains other parts of the feeding motor generator since a coordinated output of appropriately phased hyperpolarizing waves, antagonistic EPSP volleys, motor bursts, and movements is simultaneously recorded in other, unstimulated motor neurons of the system. However, the SW neurons are not always entrained by such MN-generated bursting. 6. Brief stimulation of B5 (sufficient to elicit one or a few impulses) also results in the appearance of a depolarizing afterpotential, which is itself capable of regenerating further impulses. When prolonged, constant currents are applied, the impulses that result form bursts whose durations and interburst intervals depend on the amplitude of the stimulating currents. The spike and burst-generating qualities of these neurons (which may include endogenous and interactive components) are sufficient to serve as a source of timing and phasing for the motor pattern. PMID- 6255110 TI - Control of multiple impulse-initiation sites in a leech interneuron. AB - 1. Several heart interneurons (HN cells) of the leech nerve cord have impulse initiation sites in every segmental ganglion through which their single axons pass. All these initiation sites are capable of producing rhythmic impulse bursts. However, under normal conditions a dominant primary initiation site in the ganglion where the cell body is located suppresses the activity of the other secondary sites. 2. Hyperpolarization of the primary initiation site by injected current permits immediate expression of rhythmic activity by a secondary site, usually the one located in the next posterior ganglion. 3. The free-running impulse burst rhythm of the primary site is stronger than that of the secondary site, having a greater burst duration and a tendency toward a higher burst frequency. 4. Bursts of primary-site impulses intercalated into the secondary site impulse burst rhythm have a twofold effect. First, early to midway through the secondary-site's burst cycle, they phase delay its impulse burst rhythm. Second, early in the secondary-site's burst cycle, they tend to suppress ongoing impulse bursts, and late in the secondary-site's burst cycle, they tend to suppress the next expected impulse burst. The amount of burst suppression seen early and late in the secondary-site burst cycle depends on the burst duration and intraburst impulse frequency of the intercalated burst. 5. The ability of a train of primary-site impulse bursts to completely suppress secondary-site activity depends on burst duration, intraburst impulse frequency, and burst period. 6. Primary-site impulse trains with burst parameters close to those of naturally occurring primary-site bursts completely suppress secondary-site activity. 7. These results are consistent with the notion that the primary-site impulse burst rhythm of an HN cell suppresses the activity of its secondary site because, cycle by cycle, it delays and/or suppresses the next secondary-site burst so that no secondary-site bursts are produced. Dominance of the primary site over the secondary site is ensured by virtue of the primary-site's stronger impulse burst rhythm. PMID- 6255112 TI - Cerebral vasospasm: contractile activity of hemoglobin in isolated canine basilar arteries. PMID- 6255111 TI - Influence of raphe nuclei on neuronal transmission from perforant pathway through dentate gyrus. AB - 1. In chronically prepared, freely moving rats, electrical stimulation was applied to the perforant pathway and monosynaptic responses were recorded extracellularly in the ipsilateral dentate gyrus. In some tests a stimulus was also applied to the median raphe nucleus (mr) prior to activating the perforant pathway. Experiments were performed during two behavioral conditions: slow-wave sleep (SWS) and the still, alert state (SAL). Two varieties of evoked responses were recorded: those due to synchronous firing of neuronal action potentials (evoked action potentials or EAPs) and those produced by excitatory synaptic activity (evoked synaptic potentials or ESPs). 2. As reported previously (38), perforant path stimulation elicited EAPs of greater magnitude during SWS than during SAL. The application of a prior stimulus to mr (prestimulation) markedly increased the already elevated EAPs observed during SWS. The EAPs during SAL were unaffected by prestimulation. 3. The minimum delay time (time between mr and perforant path stimuli) at which the augmentation of the EAPs appeared during SWS was approximately 5 ms. The augmentation reached a maximum at delay times of 25 40 ms and was present up to a delay time of 150 ms. 4. As in former experiments (38), ESPs recorded in the molecular layer of the dentate gyrus after perforant path stimulation were found to be greater during SAL than during SWS. Prestimulation of mr had no significant effect on the ESPs at any level of the molecular layer during either SWS or SAL. 5. The perforant path afferent volley was recorded at high gain in the dentate gyrus. Its amplitude was found to be solely dependent on perforant path stimulus intensity and not on behavioral state or the prestimulation of mr. 6. In preparations anesthetized with Chloropent (82% chloral hydrate, 18% pentobarbital; Fort Dodge Laboratories, Fort Dodge, IA), prestimulation was applied at each of a number of loci within the pons and medulla, including mr, As in SWS, prestimulating mr resulted in augmented EAPs with a minimum delay time of 5 ms. Similar augmented responses were observed when stimulation was applied at other raphe nuclei (dorsal raphe, pontis, magnus, and pallidus), but there was no augmentation when stimulation was applied at other brain stem sites. Threshold stimulus intensities for producing augmented EAPs in the raphe nuclei were less than 30 microA. 7. In freely moving animals it was first established that the EAP responses during SWS were markedly greater than during SAL. Midline lesions were then made at the rostrocaudal level of mr. Following the lesions, there was no longer any significant difference in the magnitude of the EAPs recorded during the two behaviors. 8. These findings suggest that tonic influences arising from raphe nuclei during SWS may be involved in the facilitation of neuronal transmission through the dentate gyrus observed during this behavioral state. PMID- 6255113 TI - Cysts in malignant gliomas. Identification by computerized tomography. AB - The clinical course, computerized tomography (CT) scans, and postmortem reports for 265 patients treated for malignant brain tumors were reviewed. Forty-one patients underwent reoperation for tumor recurrence and one had needle aspiration as a diagnostic procedure; of these patients, seven (3% of 265 and 17% of 42) were diagnosed as harboring tumor cysts and 10 (25% of 41) as having necrotic tumor centers. The CT scans on the 17 patients harboring tumors with surgically confirmed cysts and necrotic centers were reviewed; criteria for distinguishing between cysts and central necrosis are suggested. The relative benefits of repeated aspiration and surgical therapy for these cystic lesions are discussed. PMID- 6255114 TI - Optimal handling of dimercaptosuccinic acid for quantitative renal scanning. AB - Methods of optimizing quantitative renal imaging with Tc-99m dimercaptosuccinic acid (DSMA) were investigated. Rats were injected with DMSA (one kit per rat) and sacrificed at 0.5, 2.0, and 24 hr after injection. Fifty percent of the injected dose localized in the kidneys at 0.5, 2, and 24 hr after injection while background activity peaked at 0.5 hr and then declined to give substantially higher kidney-to-background ratios at 24 hr. Delayed scanning should increase the accuracy of clinical studies in patients with low kidney-to-background ratios at 1-2 hr. After injection of DMSA, 1 ml of air was introduced into the reaction vials and incubated 20 min. Kidney uptake decreased from 50 to 40% and liver uptake increased from 7.5 to 17%. If multiple doses must be drawn from a single vial, air should not be introduced, and the doses should be drawn together and administered immediately to minimize radiopharmaceutical deterioration. PMID- 6255115 TI - Time-course of changes of liver tryptophan pyrrolase (tryptophan oxygenase) and liver and kidney glucose-6-phosphatase in rats shifted from high- to zero-protein diets. AB - Time-courses of changes in the activities of liver and kidney glucose-6 phosphatase [EC 3.1.3.9] and hepatic tryptophan pyrrolase [EC 1.13.1.12; TPO] in rats pre-fed high-protein diets for 5 days and then shifted to zero-protein diets were studied. Liver glucose-6-phosphatase activity decreased 1 day after the dietary shift but then increased and remained significantly higher than the 0 day value for the next 2 days. Changes in liver glycogen were found to be intimately and inversely related to liver glucose-6-phosphatase activity. Changes in kidney glucose-6-phosphatase activity paralleled the pattern of changes observed in liver activity. An initial decrease in TPO activity was followed by increased enzyme activity up to the 3rd day of the dietary shift. Later there was a rapid fall in tryptophan pyrrolase activity. Changes observed in these specific enzyme proteins differed from those observed in total tissue proteins. Alterations in the activities of these enzymes and changes in other parameters are compared with those observed earlier with the reverse type of dietary shift. PMID- 6255117 TI - A community mental health center approach to aftercare: plans, problems, promises. PMID- 6255116 TI - A viable alternative to re-institutionalization of chronic mental patients. PMID- 6255118 TI - Odontoblast metabolism in rats deficient in vitamin D and calcium. IV. Lysosomal and energy metabolic enzymes. AB - Young rats, fed a low calcium and vitamin D deficient diet for 2 weeks, developed hypocalcemia, an increased activity of serum alkaline phosphatase and an increase in the serum concentration of immunoreactive parathyroid hormone. An increased activity of lactate dehydrogenase and cytochrome oxidase in odontoblasts was found. No shift in the general energy metabolic pathway was found as visualized in the lactate dehydrogenase iso-enzyme pattern. The dominating lactate dehydrogenase isoenzyme in odontoblasts from both the normal and the deficient rats was LDH 1 (H4, LD5), thus indicating primarily an aerobic energy-metabolism Also the activities of the lysosomal enzymes acid phosphatase, cathepsin D and hyaluronidase in the odontoblasts from the deficient animals were increased when compared to the normal animals. No significant change could be demonstrated for beta-glucuronidase and beta-N-acetylglucosaminidase. It was earlier found that this deficient diet caused an increase in odontoblast alkaline phosphatase activities and protein synthesis in vitro. In view of the present findings it might be concluded that the low calcium and vitamin D deficient diet causes a general increase in the odontoblast metabolism. It is not known whether this is due to the increase in parathyroid hormone or if it is a direct effect of the lowered serum calcium concentration. PMID- 6255119 TI - Neutropenia and impaired neutrophil migration in type IB glycogen storage disease. AB - The association of neutropenia with type IB glycogen storage disease was observed in siblings. Biochemical studies of liver demonstrated a defect in glucose-6 phosphate transport. Neutrophil mobilization in vivo was impaired but the bone marrow was normal histologically. In vitro studies of neutrophils indicated a defect in random and directed cell migration. The studies suggest that a role for glucose-6-phosphate transport in neutrophils should be considered. PMID- 6255120 TI - Primary Epstein-Barr virus infection in association with Reye syndrome. PMID- 6255121 TI - Neutropenia in a patient with type IB glycogen storage disease: in vitro response to lithium chloride. PMID- 6255122 TI - The detection of acute gastrointestinal bleeding using in vivo technetium 99m pertechnetate-labeled erythrocytes. PMID- 6255123 TI - Intrascrotal Wilms' tumor developing in a heterotopic renal anlage of probable mesonephric origin. AB - A case of intrascrotal primary Wilms' tumor is reported. The histopathologic appearance of the primary tumor and subsequent pulmonary metastasis are identical with that of a typical intrarenal Wilms' tumor. The origin of this tumor in a heterotopic renal anlage consistent with mesonephric origin suggests that tissue from the intermediate and caudal segments of the nephrogenic cord may produce Wilms' tumor. Wilms' tumor arising in an embryologic rest of renal tissue is a rare occurrence. We are reporting the seventh well-documented case and the first case with confirmed distant metastasis. PMID- 6255124 TI - Stimulation of lysosomal enzyme release from macrophages by lipoteichoic acid. PMID- 6255125 TI - The cyclic nucleotide content of the rat superior cervical ganglion. PMID- 6255126 TI - Maturation of sympathetic neurotransmission in the rat heart. VI. The effect of neonatal central catecholaminergic lesions. PMID- 6255127 TI - Cyclic nucleotides and contraction/relaxation in airway muscle: H1 and H2 agonists and antagonists. PMID- 6255128 TI - Hydrocortisone and human lymphocytes: increases in cyclic adenosine 3':5' monophosphate and potentiation of adenylate cyclase-activating agents. AB - We have investigated the effect of hydrocortisone on the cyclic adenosine 3':5' monophosphate (cAMP) response of human lymphocytes and polymorphonuclear leukocytes. Hydrocortisone (10(-6)-10(-3)M) caused a dose-dependent increase in the cAMP content of human lymphocytes which occurred rapidly (within 1 min); the cAMP level peaked at about 10 min, remained elevated for 90 min and decreased promptly to base line if the cells were washed free of hydrocortisone. In contrast to its effects on lymphocytes, hydrocortisone caused only a small dose dependent increase in cAMP content of polymorphonuclear leukocytes which became significant only at high concentrations. In addition to increasing lymphocyte cAMP levels, hydrocortisone (10(-6)-10(-3)M) markedly potentiated the effect of many adenylate cyclase-stimulating agents including beta adrenergic stimuli, histamine, adenosine, prostaglandin E1 and cholera enterotoxin. The biochemical mechanism(s) of these actions of hydrocortisone were explored and it was found that hydrocortisone exerted its effects neither by blocking extracellular cAMP efflux, nor by inducing protein synthesis, nor by activating prostaglandin metabolic pathways, nor by preventing receptor (e.g., beta adrenergic receptor) desensitization. Hydrocortisone probably does not work as a cAMP phosphodiesterase inhibitor, since it did not inhibit lymphocyte phosphodiesterase, and the magnitude of synergistic potentiation by hydrocortisone was greater than that of potent phosphodiesterase inhibitors. Thus, hydrocortisone might act on the adenylate cyclase enzyme system by other, unknown mechanism(s). The ability of hydrocortisone to increase cAMP and especially to potentiate adenylate cyclase-stimulating agonists may partly explain the potent in vivo anti-inflammatory effect of corticosteroids in man. PMID- 6255129 TI - The ionic mechanism of prolongation of action potential duration of cardiac ventricular muscle by anthopleurin-A and its relationship to the inotropic effect. AB - Anthopleurin-A (AP-A) prolonged the duration of action potential and increased the developed tension of isolated guinea-pig and canine ventricular muscle. Voltage clamp experiments by using a single sucrose gap method were performed to investigate the ionic mechanism of the prolongation of the action potential in guinea-pig ventricular muscle. The prolongation of action potential by AP-A was accompanied by a decreased net outward current in a quasi-steady state. The slow inward current and the delayed potassium current were not changed by AP-A. The prolongation of action potential by AP-A was reversed by tetrodotoxin, thus it was concluded that AP-A induced tetrodotoxin-sensitive inward current which lasted long after the initial fast Na current. Modification of the AP-A-induced positive inotropic effect was also examined by using the canine blood-perfused ventricular muscle and was consistent with the above electrophysiological effects; tetrodotoxin, not nifedipine, suppressed percent changes produced by AP A and also that by veratrine. PMID- 6255130 TI - Different mechanisms of action of acetazolamide and parathyroid hormone on proximal tubular absorption of fluid and 5,5-dimethyl-2,4-oxazolidinedione. AB - The effects of acetazolamide (Diamox), parathyroid hormone (PTH) and dibutyrylcyclic-adenosine 3':5'-monophosphate (db-cAMP) on fluid and 5,5-dimethyl 2,4-oxazolidinedione (DMO) absorption in the rat proximal convoluted tubule were studied by using microperfusion methods. The rate of tubular absorption of DMO was used to estimate the rate of hydrogen ion secretion. When the tubular and the peritubular capillaries were perfused simultaneously with bicarbonate-free Ringer's solution containing DMO, the rate of DMO absorption (JDMO) was 140 +/- 15.7 pmol/min . mm, a value comparable to the rate of absorption of bicarbonate and glycodiazine, and net fluid absorption (JV) was 2.20 +/- 0.19 nl/min . mm. Administration of PTH (10(-6) M) to the capillary perfusate caused a decrease of JDMO by 23% and a decrease of JV by 28%. Similar results were observed when db cAMP (10(-4) M) was administered to the luminal perfusate. Addition of acetazolamide (10(-4) M) to the luminal perfusate caused a decrease of JDMO by 66% and a decrease of JV by 45%. The effect of either PTH or db-cAMP was additive to the maximal effect of acetazolamide. However, the effect of PTH was not additive to the effect of db-cAMP. Thus, the results suggest that PTH and acetazolamide have different mechanisms of action on fluid and DMO absorption by proximal tubule and that cAMP mediates the effect of PTH. PMID- 6255131 TI - Phenytoin inhibition of cyclic guanosine 3':5'-monophosphate (cGMP) accumulation in neuroblastoma cells by calcium channel blockade. AB - Phenytoin (diphenylhydantoin) inhibits the calcium-dependent increases in guanosine 3':5'-monophosphate (cGMP) produced by high potassium depolarization and by muscarinic receptor activation in N1E-115 neuroblastoma cells. The inhibition of the cGMP response to depolarization is half-maximal at 40 microM, similar to the plasma concentration associated with an optimal therapeutic response. The cGMP increase produced by the cationophore A23187 is insensitive to phenytoin blockade, indicating that the enzymatic machinery responsible for calcium-stimulated cGMP accumulation is not affected. The calcium concentration response curve for the cGMP response to high potassium showed that phenytoin acted primarily to reduce the maximal response. The corresponding curve for the cGMP response to acetylcholine showed apparent competitive inhibition by phenytoin whereas the acetycholine concentration-response curve showed noncompetitive inhibition by phenytoin. The results suggest that phenytoin inhibits cGMP responses by blocking calcium influx. The ability to block the depolarization-induced cGMP response is shared by other anticonvulsants which are effective against generalized tonic-clonic and cortical focal seizures but not by those effective against absence seizures. PMID- 6255132 TI - Regulation of serotonin2 (5-HT2) receptors labeled with [3H]spiroperidol by chronic treatment with the antidepressant amitriptyline. AB - Recently, we reported that chronic administration of several antidepressants of different classes produced larger reductions in numbers of serotonin2 (5-HT2) receptors in rat brain labeled by [3H[spiroperidol than in beta adrenergic receptors. In the present study, we examine detailed properties of 5-HT2 receptor regulation by chronic treatment with amitriptyline. Chronic but not acute treatment with the tricyclic antidepressant amitriptyline reduces binding to 5 HT2 receptors by [3H]spiroperidol and beta adrenergic receptor binding of [3H]dihydroalprenolol in brain membranes. The decrease is time-dependent, gradually reversible and represents a change in the number of binding sites with no alteration in drug affinities for 5-HT2 receptors. The effect can be observed at daily doses of 2.5 mg/kg, similar to clinically effective doses in humans. At all doses and time intervals, the decrease in 5-HT2 receptors is more marked than the concurrent change in total beta adrenergic receptor binding. The properties of 5-HT2 receptor reduction after chronic antidepressant treatment indicate that this alteration could be associated with therapeutic response. PMID- 6255133 TI - Maturation of sympathetic neurotransmission in the rat heart. V. Development of baroreceptor control of sympathetic tone. PMID- 6255134 TI - Electrophysiological evidence for presynaptic actions of phencyclidine on noradrenergic transmission in rat cerebellum. AB - The actions of the psychotomimetic drug phencyclidine (PCP) were studied using Purkinje neurons in the cerebellum of urethane-anesthetized rats. PCP, applied by micropressure ejection through multibarreled micropipettes, depressed the spontaneous activity of these neurons as recorded by extracellular electrophysiological techniques. This depressant effect was blocked by neuroleptic drugs and lithium, both of which also block the depressant effects of norepinephrine, but not those of gamma-aminobutyric acid. PCP-elicited depressions could not be obtained in rats in which the cerebellar noradrenergic terminals had been lesioned selectively by pretreatment with the neurotoxin 6 hydroxydopamine. However, PCP was still an effective depressant in animals after destruction of non-noradrenergic intrinsic excitatory and inhibitory interneurons which synapse on the Purkinje cell by neonatal X-irradiation. Further treatment of the X-irradiated animal with 6-hydroxy-dopamine resulted in Purkinje neurons which were not responsive to PCP. Administration of magnesium ions, which reduces the release of neurotransmitters from afferent terminals, also blocked the depressant effects of PCP. The results of this study suggest that PCP acts in the cerebellum by a presynaptic mechanism involving the release of norepinephrine from intact, functioning noradrenergic terminals. PMID- 6255135 TI - Comparative studies of the pharmacological effects of the d- and l-isomers of codeine. AB - Opiates are known for their stereospecificity. The following studies show that l codeine was active in the mouse tail-flick test as well as in the hot plate test whether given p.o. or s.c. The ED50 in the first test was 4.09 mg/kg s.c. (2.01 8.34 mg/ kg) and 13.41 mg/kg p.o. (6.91-26.0 mg/kg). In the second antinociceptive test, the ED50 was 20.66 mg/kg s.c. (11.52-37.08 mg/kg) and 20.47 mg/kg p.o. (14.63-28.57 mg/kg). The d-isomer of codeine was inactive ina both tests up to 100 mg/kg but caused hyperexcitability, convulsions and ultimately death. Although l-codeine was more potent than d-codeine inhibiting the cough reflex in the anesthetized cat, the d-compound did have good activity. The ED50 of the l-isomer was 0.27 mg/kgi.v. (0.14-0.47 mg/kg) and that of the d-isomer was 1.61 mg/kg i.v. (0.98-2.65 mg/kg). In these animals, l-codeine did not significantly affect the cardiovascular parameters at the doses tested, whereas d codeine caused a significant but transient decrease in the blood pressure and heart rate. The specific and nonspecific properties of d- and l-codeine were further delineated in the opiate receptor binding assay. l-Codeine inhibited the stereospecific binding of 2.2 x 10(-9) M [3H]dihydromorphine in mouse brain homogenate with the IC50 being 1.6 x 10(-5) M (1.2 x 10(-5)--2.0 x 10(-5) M). d Codeine had no effect up to 10(-4) M. PMID- 6255136 TI - Actions of mu, kappa, sigma, delta and agonist/antagonist opiates on striatal dopaminergic function. PMID- 6255137 TI - The effect of theophylline and other methylxanthines on presynaptic inhibition of the longitudinal smooth muscle of the guinea pig ileum induced by purine nucleotides. PMID- 6255138 TI - Specific changes in the cholinergic system in guinea-pig vas deferens after denervation. AB - A small rapid phase (1st phase) was distinguished from a concomitant phase (2nd phase) in contraction of guinea-pig vas deferens. The vas deferens 4 days after denervtion exhibited supersensitivity to stimulants. The supersensitivity in the 2nd phase of contraction was nonspecific, but that in the 1st phase was specific to muscarinic cholinergic agonists. The increase in sensitivity resulted in a shift of the dose-response curve to lower concentrations without significant change in the maximal response. Muscarinic cholinergic receptors in the vas deferens, determined by measuring binding of [3H]quinuclidinyl benzilate, changed after denervation. The maximal binding sites increased from 115 to 165 fmol/mg of protein with no significant change in the dissociation constant. The affinity of the receptor for agonist also did not change significantly. Studies on [3H]WB4101 binding indicated no significant change in alpha adrenergic receptors after denervation. Thus, specific supersensitivity of the cholinergic mechanism mediated by muscarinic acetylcholine receptors occurred after denervation of guinea-pig vas deferens. This increased sensitivity is discussed in relation to the amount of receptor. PMID- 6255139 TI - Release of prostaglandins from the isolated frog ventricle and associated changes in endogenous cyclic nucleotide levels. AB - 1. A study has been made of the decline in contractility and some associated metabolic changes which occur in the isolated frog ventricle during the development of hypodynamic depression. 2. The release of two identified prostaglandins (PG), E1 and E2, together with several as yet unknown prostaglandin-related substances (PRS), accompanies the development of hypodynamic depression. There is a close correlation between the extent to which the isometric twitch is depressed and the quantity of prostaglandin released into the superfusate. 3. Fractionation of extracts of 'used' superfusates, using preparative-scale thin-layer chromatography, revealed the presence of six major components, four of which (PGE1 and PGE2 and two unidentified components) were found to be cardioactive and potentiated contraction when tested subsequently on hypodynamic preparations. 4. Two agents which influence prostaglandin biosynthesis, arachidonic acid and indomethacin, are found to affect both the rate at which the hypodynamic state develops and the extent to which the 'steady state' twitch tension is depressed, in a dose-dependent manner. Indomethacin, a PG-synthetase inhibitor, accelerates the decay and depresses the final 'steady state' tension attained, whereas arachidonic acid, the principal precursor for prostaglandin biosynthesis, has the converse effects. 5. Measurements of endogenous 3'5'-cyclic nucleotide levels reveal a time-dependent decrease in intracellular adenosine 3'5'-cyclic monophosphate (3'5'-cyclic AMP) and a concomitant increase in guanosine 3'5' cyclic monophosphate (3'5'-cyclic GMP). The decline in isometric twitch tension is paralleled almost exactly by an equivalent reduction in the ratio 3'5'-cyclic AMP: 3'5'-cyclic GMP. 6. Superfusion of isolated ventricles with Ringer solution containing exogenous, lipid-soluble derivatives of 3'5'-cyclic AMP and 3'5'-cyclic GMP affects both the rate of decline of the isometric twitch and the steady-state tension ultimately reached: thus, 8-bromo-3'5'-cyclic GMP accelerates the decline in contractility and depresses the steady-state level, whereas dibutyryl 3'5'-cyclic AMP delays the development of hypodynamic depression, and elevates the final twitch tension. The effects of both 3'5' cyclic nucleotide derivatives are dose-dependent. 7. The possible involvement of prostaglandins and 3'5'-cyclic nucleotides as causal agents in the mechanism of hypodynamic depression is discussed. The biochemical basis for the implied antangonistic effects of 3'5'-cyclic AMP and 3'5'-cyclic GMP in regulating ventricular contractility is considered in the following paper (Flitney & Singh, 1980). PMID- 6255140 TI - Rate-limiting step of inhibitory post-synaptic current decay in Aplysia buccal ganglia. AB - 1. In neurones BL and BR 3, 6, 8, 9, 10 and 11 of Aplysia buccal ganglia, cholinergic inhibitory post-synaptic potentials are produced by activity in either of two presynaptic cells. In order to analyse the synaptic conductance change, neurones were voltage-clamped inhibitory post-synaptic currents (i.p.s.c.) recorded. 2. The synaptic conductance change rises to an average peak value of 0.65 micromho and decays exponentially with single time constant tau of 19 msec. 3. We have attempted to identify the rate-limiting step responsible for i.p.s.c. decay from among the following possibilities: (1) acetylcholine (ACh) supply, (2) ACh removal by diffusion, (3) ACh removal by hydrolysis or (4) a slow unbinding or conformational change closing open synaptic current channels. 4. Cooling prolongs tau, with Q10 of 5.2. Cooling and eserine treatment together produce greatly prolonged, exponentially decaying i.p.s.c.s with tau > 150 msec. These results suggest that ACh removal, either by diffusion or hydrolysis, is not the rate-limiting step. 5. Prolonging synaptic action potential time course with intracellular injection of tetraethylammonium broadens the i.p.s.c. peak but does not affect the decay tail, suggesting that the rate-limiting step is not ACh release. 6. The spectrum of ACh-induced current fluctuations is fitted by a double Lorentzian with cut-off frequencies of 7.8 and 47 Hz. The frequency of the slower component corresponds to the macroscopic i.p.s.c. decay tau. 7. We conclude that a slow conformational change closing open synaptic current channels is likely to determine i.p.s.c. decay. We cannot, however, exclude either delayed diffusion or a late tail of slow ACh release as possibilities. PMID- 6255142 TI - Divalent ion currents and the delayed potassium conductance in an Aplysia neurone. AB - 1. In Na- and Ca-free external solutions, Sr or Ba (but not Mg) could act as carriers of inward current during action potentials in the neurone, R15 of the Aplysia abdominal ganglion. These action potentials exhibited a prolonged plateau phase, the duration of which was dependent on the concentration and species of divalent cation and activity of the neurone. 2. Depolarization of the soma membrane in Na-free Ba solution generated a prolonged, 'late' inward current the amplitude of which was dependent on the external Ba concentration. The Ba current was insensitive to tetrodotoxin but could be blocked by Mn2+ and Co2+ ions. 3. The peak current-voltage relation and threshold for activation of the late inward current was shifted to more negative potentials on replacement of Ca with Ba. The zero-current (reversal) potentials for both Sr and Ba were more negative than for Ca, indicating that the 'Ca' channel is less permeable to Sr2+ or Ba2+ ions than to Ca2+ ions. 4. Inactivation of the 'Ca' channel is slower in Ba than in Ca solution. The time course of Ba currents during a maintained depolarization of 2 sec could be reasonably described by the expression, I'Ba(t) = I'Ba (infinity) [1 exp(-t/tau M)]2exp(-t/tau H). 5. Time constants for activation (tau M) and inactivation (tau H) were voltage-dependent. In the range -10 to +30 mV, tau M varied from 15 to 5 msec and tau H from 2.0 to 0.5 sec (12 degrees C). Steady state Ba conductance (corrected for inactivation) was voltage-dependent, increasing sigmoidally with depolarization to a maximum of approximately 12 microS at potentials beyond +15 mV. 6. Steady-state inactivation of Ba conductance (hBa(infinity)) varied with holding potential (VH). Conditioning holding potentials more negative than the resting potential (-40 to -50 mV) produced depression of Ba currents. Complete inactivation of Ba currents occurred at holding potentials more positive than 0 mV or with repetitive activation at frequencies greater than 1 Hz. 7. The divalent ions, Ba2+ and Sr2+, reversible depressed the total delayed K+ current at a rate dependent on the frequency of activation. Ba and Sr shifted the delayed K+ current-voltage curve to more positive voltages and depressed the delayed outward current at all membrane potentials. 8. Comparison of the effect of Ba on delayed K+ currents with those obtained in the presence of Mn2+ ions indicated that Ba2+ ions depress both the voltage-dependent and Ca-dependent components of the delayed K+ current. However, the mechanism by which Ba acts to inhibit the two components of the delayed K+ current appears to be different. PMID- 6255141 TI - Inotropic responses of the frog ventricle to adenosine triphosphate and related changes in endogenous cyclic nucleotides. AB - 1. A study has been made of a well documented but poorly understood response of the isolated frog ventricle to treatment with exogenous adenosine 5' triphosphate (ATP). Measurements of membrane potential, isometric twitch tension and levels of endogenous 3',5'-cyclic nucleotides have been made at various times during the ATP-induced response. 2. ATP elicits a characteristic triphasic response, which comprises an initial, abrupt increase in contractility, rising to a maximum within a few beats (first phase); followed by a period when the twitch amplitude falls, sometimes to below the control level (second phase); and superceded by a more slowly developing and longer-lasting increase in contractile force (third phase). The response is unaffected by atropine, propranolol or phentolamine. However, the prostaglandin synthetase inhibitor indomethacin depresses the first phase and entirely suppresses the third phase. 3. The inotropic effects of ATP are accompanied by changes in the shape of the action potential. These effects are dose-related. The duration of the action potential (D-30mV) and its positive overshoot (O) are increased during all phases of the response, for [ATP]o's up to 10(-5) M. However, at higher [ATP]o's, D-30mV and O ar both reduced during the second phase (but not the first or third phase), when isometric twitch tension is also depressed. The relationship between action potential duration and twitch tension (P) for different [ATP]o's is linear for all three phases of the response, but the slopes of the curves (delta P/delta D) are markedly different, indicating that the sensitivity of the contractile system to membrane depolarization is not constant, but varies continuously throughout the response. 4. ATP has a potent stimulatory effect on the metabolism of endogenous 3',5' cyclic nucleotides. The time courses of the changes in adenosine 3','5-cyclic monophosphate (3',5'-cyclic AMP) and guanosine 3',5'-cyclic monophosphate (3',5' cyclic GMP) are complex, but the accompanying change in isometric twitch tension is paralleled closely by corresponding changes in the ratio 3',5'cyclic AMP:3',5' cyclic GMP. 5. It is concluded that ATP exerts a dual effect on the ventricle and that the contractile response is regulated by changes in the metabolism of 3',5' cyclic nucleotides. The effects of indomethacin indicate a possible involvement of prostaglandins in mediating the ATP response. It is suggested that the initial effect of ATP on the ventricle is to increase the permeability of the fibres to Ca2+. 6. The relationship between 3',5' cyclic nucleotide levels and ventricular contractility is discussed. It is postulated that the antagonistic effects of 3',5'-cyclic AMP and 3',5'-cyclic GMP are expressed at the level of certain phosphoproteins which regulate both the availability of Ca2+ and the sensitivity of the contractile proteins to Ca2+. PMID- 6255143 TI - Ephaptic transmission between single nerve fibres in the spinal nerve roots of dystrophic mice. AB - 1. Ephaptic transmission was observed between spontaneously active single nerve fibres in the spinal nerve roots of dystrophic mice. 2. In the five ephaptically interacting pairs of fibres studied in detail, the conduction velocities in the exciting fibres were < 1 m/sec and the conduction velocities in the excited fibres were 2-10 m/sec in the immediate vicinity of the ephapses at 26-28 degrees C. 3. Membrane current analysis suggested that conduction was continuous in the exciting fibres. In some cases conduction away from the ephapse in the excited fibre was saltatory in at least one and possibly in both directions of transmission. 4. It is concluded that in at least some cases the direction of ephaptic transmission is from bare axon to myelinated axon. 5. Transmission time across the ephapses, measured as the interval between peaks of inward membrane current in exciting and excited fibres, was less than or equal to microseconds 240 microseconds. 6. Ephaptic transmission is not necessarily contingent upon the direction of propagation of the impulse in the exciting fibre. 7. Ephaptic transmission between two fibres can remain stable at frequencies of at least 70 Hz. 8. There may be multiple sites of spontaneous ectopic excitation in single dystrophic mouse spinal root axons. An impulse traversing a site of ectopic excitation may incite a subsequent burst of impulses to arise from that site following a delay of more than 100 msec. PMID- 6255144 TI - Voltage clamp measurements of sodium channel properties in rabbit cardiac Purkinje fibres. AB - 1. Voltage clamp studies of the excitatory sodium current, INa, were carried out in rabbit cardiac Purkinje fibres using th two-micro-electrode technique. Previous work has shown the rabbit Purkinje fibre to have relatively simple morphology (Sommer & Johnson, 1968) and electrical structure (Colatsky & Tsien, 1979a) compared to other cardiac preparations. 2. Non-uniformities in membrane potential were kept small by reducing the size of INa to less than 50 microA/cm2 of total membrane surface area through prepulse inactivation or removal of external sodium, Nao. Temporal resolution was improved by cooling to 10-26 degrees C. These adjustments did not greatly alter the measured properties of the sodium channel. 3. Under these conditions, sodium currents were recorded satisfying a number of criteria for adequate voltage control. Direct measurement of longitudinal non-uniformity using a second voltage electrode showed only small deviations at the time of peak current. 4. The properties of the sodium channel were examined using conventional protocols. Both peak sodium permeability, PNa, and steady-state sodium inactivation, h infinity, showed a sigmoidal dependence on membrane potential. PNa rose steeply with small depolarizations, increasing roughly e-fold per 3.2 mV, and reaching half-maximal activation at -30 +/- 2 mV. The h infinity -V curve had a midpoint of -74.9 +/- 2 mV and a reciprocal slope of 4.56 +/- 0.13 mV at temperatures of 10-19.5 degrees C, and showed a dependence on temperature, shifting to more negative potentials with cooling (approximately 3 mV/10 degrees C). Recovery of INa from inactivation in double pulse experiments followed a single exponential time course with time constants of 108-200 msec at 19 degrees C for holding potentials near -80 mV. No attempt was made to describe the activation kinetics because of uncertainties about the early time course of the current. 5. These data predict a maximum duration for INa of less than 1-2 msec and a maximum peak current density of about 500 microA/cm2 under physiological conditions, i.e. 37 degrees C and 150 mM-Nao. This current magnitude is sufficient to discharge the membrane capacitance at rates comparable to those measured experimentally (311 +/- 27 V/sec, Colatsky & Tsien, 1979a). 6. The limitations of the method are discussed. The major problem is the longitudinal cable delay which limits the speed of voltage control. This makes it difficult to separate the activation of INa from the decay of the capacity transient for potentials positive to -15 mV. 7. It is concluded that the approach described is valid for measurements of sodium currents in the potential range where action potentials are initiated, making it possible to study cardiac sodium channels in an adult mammalian preparation which is free of enzymatic treatment. PMID- 6255145 TI - Synaptic modulation of calcium-dependent potassium conductance in myenteric neurones in the guinea-pig. AB - 1. Ganglion cells of the myentric plexus of the guinea-pig small intestine were studied with intracellular recording methods. 2. Electrical stimulation of the interganglionic connectives elicited slow synaptic excitation (slow e.p.s.p.) that was associated with an increase in the input resistance of the cell. The slow e.p.s.p.s continued for several seconds after termination of stimulation, and they occurred only in neurones in which prolonged hyperpolarizing after potentials followed an action potential. 3. Superfusion of the neurones with solutions containing either 1-5 mM-Mn2+ or 16 mM-Mg2+ and 1 mM-Ca2+ mimicked the slow e.p.s.p. The common characteristics of Mn2+, Mg2+ and the slow e.p.s.p. were: (a) depolarization of the membrane potential, (b) increased input resistance of the cell, (c) augmented excitability, (d) blockade of post-pike hyperpolarizing potentials and (e) reversal potential between -70 and -75 mV. 4. Analyses based on the 'constant field equation' indicated that the permeability ratios of K+ to other permeant ionic species were reduced when Ca2+ influx was blocked by Mn2+ or Mg2+. 5. The organic Ca antagonist D-600 did not affect the neurones. 6. The results suggest that slow synaptic modulation of excitability within the myenteric plexus involves a reduction of both resting GK and post spike GK which is secondary to suppression of Ca2+ influx by the neurotransmitter for the slow e.p.s.p. PMID- 6255146 TI - Hypothalamo-pituitary-adrenocortical function in rats with inherited diabetes insipidus. AB - 1. Hypothalamo-pituitary-adrenocortical activity in male homozygous and heterozygous Brattleboro rats was compared with that in normal (Long Evans) controls in an attempt to elucidate the role of vasopressin the control of the secretion of corticotrophin. 2. The concentrations of corticosterone and corticotrophin in the plasma, corticotrophin in the adenohypophyses and corticotrophin releasing factor in the hypothalami were lower in the heterozygotes than in the controls and lower still in the homozygotes. 3. The capacities of adenohypophyses and hypothalami to secrete in vitro corticotrophin and corticotrophin releasing factor respectively in response to trophic stimuli were also reduced in the heterozygotes and, to an even greater extent, in the homozygotes. 4. The results suggest that vasopressin is not the corticotrophin releasing factor but they do not exclude the possibility that it may be involved in the sequence of events which leads to the secretion of corticotrophin in the rat. PMID- 6255147 TI - Effects of tetraethylammonium chloride on sympathetic neuromuscular transmission in saphenous artery of young rabbits. AB - 1. Excitatory junction potentials and electrotonic potentials were recorded from the smooth muscle of the rabbit saphenous artery using intracellular electrodes. 2. Tetraethylammonium chloride (TEA) in concentrations greater than 3.5 mM caused depolarization. Concentrations greater than 5 mM caused spontaneous electrical activity in the form of excitatory junction potentials (e.j.p.s) and all-or nothing action potentials which were associated with spontaneous mechanical activity. 3. Concentrations of TEA less than 2.5 mM did not alter the resting potential nor the passive membrane properties of the smooth muscle over a range of +/- 15 mV. 4. The following effects were observed in 2.0 mM-TEA. (a) The minimum stimulus strength required for the initiation of an e.j.p. fell by three to fivefold. (b) Single stimuli that elicited only a small e.j.p. in normal solution evoked an all-or-nothing action potential of up to 70 mV amplitude. (c) Whereas in normal solution e.j.p.s could only be recorded up to 7 mm away from the perivascular stimulating electrode e.j.p.s could be recorded at distances of up to 13 mm. (d) The duration of the e.j.p. was prolonged. 5. Based on these results and the effects of TEA reported for other synapses it is proposed that TEA may act to increase the amount of transmitter released per axon, to increase the duration of release and to cause an increased invasion throughout the autonomic ground plexus by nerve impulses. This would imply that in normal solution, in vitro, the action potential may not propagate throughout the whole length of the terminal axon and its many branches due to failure of conduction at one or more points along the terminal portion of the axon. PMID- 6255148 TI - Properties of toxin-resistant sodium channels produced by chemical modification in frog skeletal muscle. AB - 1. Single skeletal muscle fibres from the frog Rana pipiens were treated with the carboxyl group modifying reagent trimethyloxonium ion (TMO) and voltage clamped by the method of Hille & Campbell (1976). 2. TMO treatment reduced current through sodium channels to 0.33 +/- 0.03 that before treatment, but only 45 +/- 3% of this remaining current was blocked by 1 microM-tetrodotoxin (TTX) and only 37 +/- 5% by 100 nM-saxitoxin (STX). 3. This toxin resistance persisted in 90 microM-TTX, was not due to inactivation of toxin nor to components of the reaction solution other than TMO, but was prevented by the presence of 100 nM-STX during treatment with TMO. TMO-modified sodium channels can be blocked by the local anaesthetic lidocaine. 4. The permeabilities of TMO-modified channels to hydroxylammonium, ammonium, guanidinium, aminoguanidinium, methylammonium and tetramethylammonium ions relative to sodium were not significantly different from the permeabilities of untreated sodium channels. 5. Hydrogen ions blocked TMO modified sodium channels, but the apparent pKa for block at +38 mV of 5.07 was significantly less than the corresponding value of 5.32 in untreated sodium channels. 6. It is suggested that TMO produces toxin resistance by esterifying an ionized carboxyl group which is an essential part of the toxin binding site. Such esterification would electrostatically reduce the local cation concentration, thus reducing the apparent pKa of hydrogen ion block and the single-channel conductance (Sigworth & Spalding, 1980). 7. It is concluded that the sodium channel contains a second acid group, near but distinct from an acid group previously hypothesized to be part of the selectivity filter and hydrogen ion binding site (Hille, 1971, 1972, 1975a). PMID- 6255149 TI - Barium and strontium can substitute for calcium in noradrenaline output induced by excess potassium in the guinea-pig. AB - 1. The ability of Ba2+ and Sr2+ to substitute for Ca2+ in the noradrenaline output induced by excess K+ was examined using isolated guinea-pig vas deferens. 2. When the vas deferens was repeatedly exposed to excess K+ (60 mM) at 40 min intervals, the noradrenaline output increased at least three-fold in incubation medium which contained either Ca2+, Ba2+ or Sr2+. The response decreased on repetition. The order of effectiveness was roughly Ba2+ > Ca2+ > Sr2+. 3. In the absence of excess K+, these cations had no significant stimulating effect on the noradrenaline output even when added after exposure to Ca2+-free solution. 4. As the concentration of divalent cation was increased from 0.2 to 2.5 mM the noradrenaline output induced by excess K+ increased. The maximum noradrenaline output was achieved at a divalent cation concentration of 2.5 mM and was 29.56 +/ 3.52, 15.02 +/- 1.12 and 7.45 +/- 0.84 (mean +/- S.E. of mean) n-mole/g per hr in the presence of either Ba2+, Ca2+ or Sr2+, respectively. Further increase in the concentration of the cations reduced the response. 5. The addition of either Sr2+ (2 mM) or Ca2+ (1 mM) to a solution containing various concentrations of Ba2+ facilitated the K+-induced increase in the noradrenaline output when the Ba2+ concentration was low, but inhibited release of noradrenaline when higher concentrations of Ba2+ were used. The addition of Sr2+ (1 mM) to Ca2+-containing solutions had a similar effect. 6. Mg2+ competitively inhibited the K+-induced increase in the noradrenaline output in the presence of either Ba2+ or Sr2+ and blocked that in the presence of CA2+. 7. The results indicate that both Ba2+ and Sr2+ can substitute for Ca2+ in the cations act though the same site at some stage in the process of K+-induced transmitter release. PMID- 6255150 TI - Neuromuscular transmission without sodium activation of the presynaptic nerve terminal in the lobster. AB - 1. We studed Na-independent synaptic transmission in the inhibitory synapse of the walking leg of the spiny lobster (Palinurus japonicus). 2. After loading the preparation with tetrodotoxin (TTX), brief depolarizing current injected in the inhibitory axon produced a small action potential, which propagated to the nerve terminal and gave rise to inhibitory post-synaptic potentials (i.p.s.p.) 3. The presynaptic action potential, in the presence of TTX, failed to propagate after removing Na+ in the solution. The TTX-resistant action potential was decreased, but not blocked by 30 mM-CoCl2. 4. When 4-aminopyridine (4-AP) was added to low Na+ or Na-free solution containing TTX synaptic transmission was restored. When the duration of the current pulse was increased, graded i.p.s.p. were evoked. 5. In high Ca2+ solutions containing K blockers, action potentials with prolonged duration were evoked. 6. The action potential of the presynaptic axon of the lobster neuromuscular junction depends on both Na+ and Ca2+. PMID- 6255151 TI - Plasma corticosterone in relation to adrenocorticotrophic hormone in the foetal rat. AB - The corticosterone concentration was assayed by the method of MURPHY (1967), in the plasma of the maternal and foetal rat submitted to different experimental conditions, after an isooctane washing to remove the progesterone. In foetuses, decapitated on day 18, from adrenalectomized mothers, the plasma corticosterone concentration was much lower than in the controls, on day 21. An injection of synthetic 1-24 corticotrophin at the moment of decapitation suppressed this effect. When the mother was not adrenalectomized, the plasma corticosterone values in the decapitated foetuses were near the control levels. This last finding confirms the transfer of corticosteroids through the placenta from the mother to the foetus. An injection of 1-24 corticotrophin to normal foetuses, on day 18, produces a large increase in plasma corticosterone in comparison with the control foetuses, on day 21. PMID- 6255152 TI - Influences of heparin on ACTH distribution and immunoreactivity in plasma of the rat. In vivo and in vitro studies. AB - 1. Blood samples from non-pregnant female rats were incubated in vitro with porcine 125I-ACTH, and the corresponding plasmas were chromatographed on fine Sephadex G 50. When heparin was added in vivo or in vitro, almost all the radioactivity appeared in the void volume of the columns; the same was observed when labelled ACTH was added to heparin-containing saline. In contrast, when NaCl instead of heparin was added to the blood in vivo as well as in vitro, almost all the plasma radioactivity was eluted later, with 125I-ACTH. 2. When labelled ACTH was i.v. administered to pregnant females, it was eluted in the void volume in the presence of heparin, and further down in its absence. 3. The same plasma samples from non-stressed or ether-stressed females were radioimmunoassayed for ACTH, with and without heparin. The degradation of ACTH was greater in the presence of heparin, and plasma ACTH concentration was understimated for low blood levels of heparin (5 UI/ml or less) and in contrast overestimated for high ones (25 or 50 UI/ml). 4. In conclusion, the reported data clearly demonstrated firstly that heparin added to rat blood traps ACTH molecules, promoting the formation of aggregates with apparent height molecular weight; secondly that heparin interferes with the direct radioimmunoassay of ACTH in the plasma. PMID- 6255153 TI - Denial as an effective mechanism to allay anxiety following a stressful event. PMID- 6255154 TI - Women and mental illness: a sexist trap? Part Two. PMID- 6255155 TI - Why parents anonymous? PMID- 6255156 TI - Childhood cancer is a family crisis: a review. PMID- 6255157 TI - [Ultrasonic findings of parotid tumours in 40 patients]. AB - Ultrasonic findings of 40 parotid tumours are presented in this paper. After a technical description proceeding they show the ultrasonic pattern of the three main types of parotid tumours: mixed tumours, adenolymphomas and carcinomas. The differential diagnosis between malignancy and non malignancy is carried out in 87,5% of cases. This rate of success is, according to literature data, similar to that of sialography. Since it is non invasive, the authors recommend sonography in the assessment of parotid tumours, rather than sialography. PMID- 6255158 TI - The extracellular and intracellular roles of hydroxy-eicosatetraenoic acids in the modulation of polymorphonuclear leukocyte and macrophage function. PMID- 6255159 TI - Calcium pyrophosphate crystal formation in aqueous solutions. AB - Pseudogout is characterized by the deposition of calcium pyrophosphate dihydrate, triclinic [CPPD(T)] and calcium pyrophosphate dihydrate, monoclinic [CPPD(M)] crystals in articular connective tissues. We studied aqueous solutions over a range of calcium chloride/sodium pyrophosphate concentrations to determine the ionic conditions under which these particular salts form. At 37 degrees C, CPPD(T) forms when [PPi]t greater than or equal to 10(-4), while formation of CPPD(M) occurs at 10(-3) M < [PPi]t less than or equal to 10(-2) M. When [Na+]t > 120 mM, calcium disodium pyrophosphates precipitate. With 1 mM Mg++, CPPD(M) forms at [PPi]t > 10(-3) M, mixed with a calcium magnesium pyrophosphate at [PPi]t greater than or equal to 10(-2) M. We conclude that CPPD(T) and CPPD(M) crystals form in a restricted ratio and range of [Ca++]t and [PPi]t and that other ions, particularly Mg++ and Na+, affect the nature of the crystal products formed. PMID- 6255160 TI - Evidence for natural infection with group B in coxsackieviruses in bonnet monkeys. PMID- 6255161 TI - Ba2+-induced conductance fluctuations of spontaneously fluctuating K+ channels in the apical membrane of frog skin (Rana temporaria). AB - We studied the influence of mucosal Ba2+ ions on the recently described (Zeiske & Van Driessche, 1979a, J. Membrane Biol. 47:77) transepithelial, mucosa towards serosa directed K+ transport in the skin of Rana temporaria. The transport parameters G (conductance), PD (potential difference), Isc (short-circuit current, "K+ current"), as well as the noise of Isc were recorded. Addition of millimolar concentrations of Ba/+ to the mucosal K+-containing solution resulted in a sudden but quickly reversible drop in Isc. G and Isc decreased continuously with increasing Ba2+ concentration, (Ba2+)o. The apparent Michaelis constant of the inhibition by Ba2+ lies within the range 40-80 microM. The apical membrane seems to remain permselective for K+ up to 500 microM (Ba2+)o. Higher (Ba2+)o, however, appears to induce a shunt (PD falls, G increases). This finding made an accurate determination of the nature of the inhibition difficult but our results tend to suggest a K+-channel block by K+-Ba2+ competition. In the presence of Ba2+, the power spectrum of the K+ current shows a second Lorentzian component in the low-frequency range, in addition to the high-frequency Lorentzian caused by spontaneous K+-channel fluctuations (Van Driessche & Zeiske, 1980). Both Lorentzian components are only present with mucosal K+ and can be depressed by addition of Cs+ ions, thus indicating that Ba2+ ions induce K+-channel fluctuations. The dependence of the parameters of the induced Lorentzian on (Ba2+)o shows arise in the plateau values to a maximum around 60 microM (Ba2+)o, followed by a sharp and progressive decrease to very low values. The corner frequency which reflects the rate of the Ba2+-induced fluctuations, however, increases quasi-linearly up to 1 mM (Ba2+)o with a tendency to saturate at higher (Ba2+)o. Based on a three-state model for the K+ channel (having one open state, one closed by the spontaneous fluctuation and one blocked by Ba2+) computer calculations compared favorably with our results. The effect of Ba2+ could be explained by assuming reversible binding at the outer side of the apical K+ channel, thereby blocking the open channel in ;competition with K+. The association-dissociation of Ba2+ at its receptor site is thought to cause a chopping of the K+ current, resulting in modulated current fluctuations. PMID- 6255162 TI - Action of glucosamine on acetylcholine-sensitive channels. AB - The action of glucosamine was studied on voltage clamped neurones of Aplysia, presenting an excitatory response to acetylcholine. Noise and relaxation experiments show that glucosamine increases the mean channel open time and reduces the amplitude of the elementary current associated with the acetylcholine response. Both effects are enhanced by hyperpolarization of the cell membrane. The results are interpreted by a model assuming glucosamine binding to open channels. This binding impedes the flow of permeant ions and decreases the closing rate of the channels. PMID- 6255163 TI - DNA sequence of a T4 transfer RNA gene cluster. PMID- 6255164 TI - Identification of the divalent metal ion binding domain of myosin regulatory light chains using spin-labelling techniques. PMID- 6255165 TI - Complex structure of the membrane nuclease of Streptococcus pneumoniae revealed by two-dimensional electrophoresis. PMID- 6255166 TI - Long range base pairing in bacteriophage phi X174 single-stranded DNA. PMID- 6255167 TI - Genomic organization of the 87A7 and 87Cl heat-induced loci of Drosophila melanogaster. PMID- 6255169 TI - Increases of cyclic AMP intracellular levels and cardiac relaxation. PMID- 6255168 TI - Myocardial beta-adrenergic receptors in the stroke-prone spontaneously hypertensive rat. PMID- 6255170 TI - Lysosomal hydrolases in the heterotopically isotransplanted heart undergoing atrophy. PMID- 6255171 TI - Studies on choline ad ethanolamine phosphoglyceride biosynthesis in developing rabbit brain. AB - Activities of cholinephosphotransferase (EC 2.7.8.2) and ethanolaminephosphotransferase (EC 2.7.8.1) were evaluated in microsomal preparations derived from rabbit cerebrum. Animals ranged in age from nineteen days' gestation through two months of postnatal development. Under optimal conditions the properties of these transferases in rabbit brain were remarkably similar relative to pH, divalent cation requirements, and apparent-Km values for the CDP-intermediates and the lipid acceptor, respectively. Cholinephosphotransferase-specific activity exhibited a dramatic rise during the last 15%-20% of fetal life and a second rise to a maximum near the 15th postnatal day. Ethanolaminephosphotransferase-specific activity exhibited a similar, but less striking age-related increase during the same period. Growth of rabbit cerebrum as determined by weight, increased 30-fold during this same period (24 days gestation to the 19th postnatal day). Specific activities of these transferase were similar in brain preparations from mid-fetal and early adult rabbits. The maximum specific activity of cholinephosphotransferase exceeded that of ethanolaminephosphotransferase by 3-4-fold. Age-related changes in the specific activities of these transferases appear to correlate with the developmental pattern of morphological and compositional events occurring in rabbit cerebrum during the last third of gestation and the first three weeks of postnatal life. PMID- 6255172 TI - Proviruses of mouse mammary tumor virus in normal and neoplastic tissues from GR and C3Hf mouse strains. AB - We analyzed two experimental situations to assess the role of endogenous mouse mammary tumor virus (MMTV) DNA in the genesis of mammary carcinomas. (i) GR mice carry in their germ line one or more proviruses indistinguishable by limited restriction mapping from the proviruses introduced into cells by experimental infection with the highly tumorigenic virus isolated from GR mouse milk, MMTV(GR). Most tumors arising in GR mice contain one or more proviruses at various sites in tumor DNA in addition to those present endogenously. Detection of these new proviruses is possible as a consequence of the clonal or quasiclonal character of the tumors. (ii) C3H/He mice carry three units of endogenous viral DNA, none of which resembles the DNA of the commonly encountered strains of milk borne MMTV. Nevertheless, MMTV-associated tumors arise late in life when these animals are removed from the influence of milk-borne virus; the responsible agent, MMTV(C3Hf), can also produce tumors in BALB/c mice. We found that tumors arising in both C3Hf/He mice and BALB/c mice infected with MMTV(C3Hf) were clonal or quasiclonal and contained one or more new copies of proviral DNA at various sites in the host genome. These new proviruses were readily distinguished from the proviruses of the common milk-borne virus strains and closely resembled unit II of endogenous MMTV DNA (Cohen et al., J. Virol., 32:483-496). Thus, in both experimental systems, we found evidence for new proviruses in mammary tumors, despite the preexistence of similar or identical proviruses in the germ line. The results suggest that the repositioning of MMTV proviruses may be required for the full expression of the oncogenic potential of endogenous MMTV DNA. PMID- 6255173 TI - Association of simian virus 40 T antigen with replicating nucleoprotein complexes of simian virus 40. AB - An immunoprecipitation assay was established for simian virus 40 T-antigen-bound nucleoprotein complexes by means of precipitation with sera from hamsters bearing simian virus 40-induced tumors. About 80% of simian virus 40 replicating nucleoprotein complexes in various stages of replication were immunoprecipitated. In contrast, less than 21% of mature nucleoprotein complexes were immunoprecipitated. Pulse-chase experiments showed that T antigen was lost from most of the nucleoprotein complexes concurrently with completion of DNA replication. T antigen induced by dl-940, a mutant with a deletion in the region coding for small T antigen, was also associated with most of the replicating nucleoprotein complexes. Once bound with replicating nucleoprotein complexes at the permissive temperature, thermolabile T antigen induced by tsA900 remained associated with the complexes during elongation of the replicating DNA chain at the restrictive temperature. These results suggest that simian virus 40 T antigen (probably large T antigen) associates with nucleoprotein complexes at or before initiation of DNA replication and that the majority of the T antigen dissociates from the nucleoprotein complexes simultaneously with completion of DNA replication. PMID- 6255174 TI - Free viral DNA in BK virus-induced hamster tumor cells. AB - The biological properties of nine clonal lines of BK virus-induced hamster tumor cells were studied. All clonal lines were oncogenic and showed an enhanced ability to form colonies in semisolid medium. The cells of each clonal line contained T antigen; no virus could be rescued from any of the clonal lines. The number of viral DNA copies was determined in three of the clonal lines and varied from 10 to 20 copies per diploid amount of cell DNA. The state of the viral genome was studied in these lines, and the great majority of the viral DNA molecules appeared to be present as free (nonintegrated) molecules. At least six length classes of free defective BK virus DNA molecules, which all lacked a part of the late region of the genome, were detected in these cells. Three of the six length classes of BK virus DNA molecules acquired a TaqI recognition site, which suggested substitution of cellular DNA. PMID- 6255175 TI - Analysis of secondary modifications of mouse mammary tumor virus proteins by two dimensional gel electrophoresis. AB - The structural proteins of mouse mammary tumor virus (MMTV) were analyzed by two dimensional electrophoresis on isoelectric focusing and sodium dodecyl sulfate gels. Many of the viral proteins displayed heterogeneity in charge due to variable contents of carbohydrates (in particular, sialic acid) and phosphate residues. Neuraminidase treatment of the virions influenced the isoelectric pattern of the envelope glycoproteins. The glycoproteins of an MMTV variant which was attenuated by replication in feline kidney cells had different isoelectric points. This suggested that the acquisition of an altered carbohydrate configuration had changed the host range of the virus. The major MMTV structural core protein, p27, consisted of two species, which had identical iodinated tryptic peptide compositions but differed in phosphate contents. Another MMTV phosphoprotein, p21, was separated into four different phosphorylated species. Phosphorylation of p21 could be performed in vitro by the MMTV virion-associated protein kinase. This enzyme also has a high affinity for MMTV p30 as a substrate. Possible functions of this enzyme are discussed. PMID- 6255177 TI - Altered synthesis and processing of oligosaccharides of vesicular stomatitis virus glycoprotein in different lectin-resistant Chinese hamster ovary cell lines. AB - To determine the particular intracellular steps in the glycosylation of the vesicular stomatitis virus (VSV) glycoprotein that were altered in several lectin resistant CHO cell lines, VSV-infected parental and mutant cells were pulse labeled for 30 and 120 min with [3H]mannose and [3H]glucosamine. Cell-associated viral glycopeptides were analyzed by gel filtration combined with specific glycosidase digestions and compared with the corresponding mature virion oligosaccharides. The intracellular glycosylation of the VSV glycoprotein in a mutant cell line resistant to phytohemagglutinin was identical to that in the normal cells except for a complete block in processing at a specific step in the final trimming of the oligomannosyl core from five to three mannoses. The results demonstrated that a double-mutant cell line selected from the phytohemagglutinin resistant cells for resistance to concanavalin A had an additional defect in one of the earliest stages of glycosylation, resulting in smaller precursor oligosaccharides linked to protein. PMID- 6255176 TI - Structure and processing of the mouse mammary tumor virus glycoprotein precursor pr73env. AB - The polyprotein precursor to the envelope glycoproteins of mouse mammary tumor virus was investigated by using subcellular fractionation procedures, pactomycin mapping techniques, tunicamycin inhibition of glycosylation, and endo-beta-N acetyl glucosaminidase H-catalyzed removal of glycosylated residues in order to characterize the biosynthesis and processing of the precursor. The results suggest that the precursor (Pr73env) is synthesized on the rough endoplasmic reticulum as a transmembrane protein, with the carboxyl terminus remaining on the cytoplasmic side. The apoprotein as an estimated molecular weight of 60,000 and acquires five core oligosaccharide units during synthesis. Cleavage of the precursor precedes the secondary glycosylation steps and therefore probably occurs before transport to the plasma membrane. However, a minor population of Pr73env containing complex oligosaccharides was also found in the plasma membrane. The order of the glycoproteins in the precursor, as determined by pactomycin mapping, in NH2-gp52-gp36-COOH. PMID- 6255178 TI - Efficient transcription of a compact nucleoprotein complex isolated from purified simian virus 40 virions. AB - Simian virus 40 (SV40) virions were dissociated in vitro by treatment with ethylene glycol-bis-N-N'-tetraacetic acid and dithiothreitol. The compact nucleo protein core released as a result of the dissociation had a sedimentation value of 110 to 115S compared with a value of 240S for intact virions. The viral cores contained a fraction of the viral proteins VP(1) and VP(2) in addition to the proteins found associated with the viral minichromosome, i.e., VP(3) and histones H(2)A, H(2)B, H(3), and H(4). Our results suggest that the association of VP(1), VP(2), or both with the viral minichromosome, in addition to maintaining a highly compact structure, modifies the transcriptional properties of the nucleoprotein complex. In the presence of saturating amounts of Escherichia coli RNA polymerase, 95 to 100% of the SV40 nucleoprotein cores were able to form transcriptional complexes. Sedimentation analysis of the core transcriptional complex indicated that the initiation and elongation of nascent RNA chains occurred on the compact SV40 core. Cesium chloride density gradient analysis of the SV40 virion core before and after transcription indicated that no substantial loss of protein occurred during the process of transcription. RNA synthesized from SV40 cores was a fairly homogeneous 16 to 18S species with an average chain length of approximately 2,300 nucleotides. Hybridization analysis of this RNA indicated that specific recognition of RNA polymerase promoter sites was preserved, since transcription was asymmetric, occurring preferentially on the "early" SV40 DNA strand. The rate of incorporation of ribonucleoside triphosphates into acid-insoluble RNA with SV40 cores as the template was 70 to 95% of that obtained with supercoiled SV40 form I DNA. SV40 minichromosomes, under identical transcription assay conditions, had an incorporation rate which was 20% of that obtained with SV40 form I DNA. These results show that association of protein VP(1) or VP(2) or both enhances the transcriptional activity and suggest that these "late" viral proteins may play a role in the regulation of expression of the SV40 genome. PMID- 6255179 TI - Nuclear processing of viral high-molecular-weight RNA in cells infected with herpes simplex virus type 1. AB - Nuclear RNA isolated from cells infected by herpes simplex virus type 1, strain F, was fractionated on formamide-sucrose gradients into two major classes, greater and less than 45S. These two classes of labeled nuclear RNA were hybridized to viral DNA fragments generated by digestion with the restriction enzymes HindIII and BglII. Early in infection, only a few DNA fragments hybridized to RNA, with slight differences between the two classes. Late in infection, all DNA fragments hybridized, showing that all viral RNA was present in large precursor molecules greater than 14 kilobases. The fragments that correspond to late gene products hybridized more of the small RNA than the large RNA. This suggests that the mRNA corresponding to late genes accumulated after the large precursors have been cleaved. Large (greater than or equal to 45S) and small (< 45S) nuclear RNA and cytoplasmic RNA from cells late in infection were hybridized in excess to in vitro-labeled HindIII M and L fragments. More than 50% of the HIndIII M fragment annealed with the large nuclear RNA, but only 36% of it annealed with the cytoplasmic RNA. The HindIII L fragment hybridized large nuclear RNA and cytoplasmic RNA to the same extent (30% and 26%). These results suggest that RNA complementary to the HindIII M fragment, which is the template for immediate early polypeptides, was regulated in the nuclei at the posttranscriptional level. This seems to suggest that temporal regulation of RNA cleavage occurs in the nucleus. PMID- 6255180 TI - Isolation and identification of lymphocytic and myelogenous leukemia-specific sequences in genomes of gibbon oncornaviruses. AB - Five gibbon ape leukemia virus substrains (two from gibbons with lymphocytic leukemia and three from gibbons with myelogenous leukemia) were examined for unique genomic sequences specific for each form of leukemia. By using sequential adsorption procedures, the genome from each gibbon ape leukemia virus was fractionated into four sets of distinct nucleotide sequences. Based on their hybridization specificities toward DNAs of leukemic tissues, these sequences were designated as follows: (i) "COM," (ii) "LYM" or "MYE," (iii) "UNI," and (iv) "UND." The COM fraction represented sequences common to all of the viral genomes. The LYM fraction, which was isolated only from gibbon ape leukemia viruses associated with lymphocytic leukemia, represented genomic sequences associated with lymphocytic leukemia since the RNA hybridized at a 4- to 15-fold-higher rate to infected tissue DNA from lymphocytic leukemic gibbons than to infected tissue DNA from myelogenous leukemic gibbons. The MYE fraction, which was isolated only from gibbon ape leukemia viruses associated with myelogenous leukemia, represented genomic sequences associated with myelogenous leukemia since the RNA hybridized at a 5- to 15-fold-higher rate to infected tissue DNA from myelogenous leukemic gibbons than to infected tissue DNA from lymphocytic leukemic gibbons. The UNI fraction contained sequences unique to one virus substrain. The UND fraction contained sequences which varied depending upon the substrains involved in the adsorption procedures. These findings suggest that each gibbon ape leukemia virus examined in this study contains subgenomic sequences that are specifically identifiable only with the form of leukemia from which the virus was isolated. PMID- 6255181 TI - Picornaviral VPg sequences are contained in the replicase precursor. AB - It has previously been shown that the RNA replicase of encephalomyocarditis virus contains two virus-coded proteins, D and E, which are produced in two successive proteolytic steps: (i) C leads to D + ?; and (ii) D leads to p22 + E. It is here shown (i) that virus protein H (molecular weight, 12,000) is the previously unidentified product of the first step and (ii) that VPg, a protein linked covalently to the virion RNA, yields two tryptic peptides found in protein C but not in protein D. The results suggest that VPg is derived by cleavage of protein C and that protein H may be intermediate. Preliminary experiments with VPg sequences in polioviral noncapsid protein 1b, the counterpart of encephalomyocarditis viral protein C, were inconclusive. PMID- 6255182 TI - Transformation phenotype of polyoma virus-transformed rat fibroblasts: plasminogen activator production is modulated by the growth state of the cells and regulated by the expression of an early viral gene function. AB - The expression of two transformation parameters, namely, ability to grow in agar and plasminogen activator production, was studied in several rat fibroblasts transformed by either wild-type or thermo-sensitive (tsa and ts25) polyoma viruses. The production of plasminogen activator was found to be dependent upon the growth state of the infected cells during a period of several days after infection. The analysis of the transformed phenotype of 25 tsa transformants and of 19 ts25 transformants independently isolated under various growth conditions led to the conclusion that there is no correlation between the regulation processes involved in plasminogen activator production and ability to grow without anchorage. The results obtained also suggested that the production of plasminogen activator is under the control of a functional large T antigen. PMID- 6255183 TI - Comparative structural analysis of glycoprotein gD of herpes simplex virus types 1 and 2. AB - We studied the synthesis and processing of the type-common glycoprotein gD in herpes simplex virus type 2 (HSV-2) and compared it structurally to glycoprotein gD of herpes simplex virus type 1 (HSV-1). We demonstrated that in HSV-2, gD undergoes posttranslational processing from a lower-molecular-weight precursor (pgD51) to a higher-molecular-weight product (gD56). Tryptic peptide analysis by cation-exchange chromatography indicated that this processing step altered neither the methionine nor the arginine tryptic peptide profile of gD of HSV-2. Comparative tryptic peptide analysis of gD of HSV-1 and HSV-2 showed that the methionine and arginine tryptic peptide profiles of these two proteins were very similar, but not identical. Some of the resolved peptides coeluted from the cation-exchange column, suggesting that some amino acid sequences of the two proteins might be very similar. However, each protein also appeared to possess several type-specific tryptic peptides. The structural similarity of these two glycoproteins correlates well with their antigenic cross-reactivity since monoprecipitin antibody to gD of HSV-1 also immunoprecipitates gD of HSV-2 and neutralizes the infectivity of both viruses to approximately the same extent. PMID- 6255184 TI - Molecular mechanism for the capture and excision of the transforming gene of avian sarcoma virus as suggested by analysis of recombinant clones. AB - Structural analysis of two cDNA clones, derived from reverse transcripts of avian sarcoma virus 21S mRNA's, reveals unusual features in the organization and expression of the integrated avian sarcoma virus (ASV) proviral DNA and predicts a mechanism for recombination events that will lead to either the capture or the excision of the transforming gene of this virus. The latter is supported by our observation that there is an extensive homologous region on either side of the transforming gene that will allow site-specific deletion or integration to occur. Comparison of the clone derived from the src-specific 21S mRNA coding for the transforming gene product to that derived from the env-specific 21S mRNA coding for the envelope glycoprotein show that the common c region present at the 3' terminus of the ASV genome is 326 bases long. Within this c region are nucleotide sequences that may play key roles in the life cycle of this virus. These regulatory sequences include (i) probable promoter sites for the initiation of transcription, (ii) a polyadenylation signal, and (iii) a sequence that is complementary to the 3' termini of both the env and the src regions, which will allow the generation of transformation-defective deletions. PMID- 6255185 TI - Spontaneous conversion of nontransformed avian sarcoma virus-infected rat cells to the transformed phenotype. AB - Normal rat kidney (NRK) fibroblasts were infected with the Schmidt-Ruppin strain (SR-D) of avian sarcoma virus (ASV) and cloned 20 h after infection without selection for the transformed phenotype. Most infected clones initially exhibited the flat, nontransformed morphology that is characteristic of uninfected NRK cells. In long-term culture, however, the majority of the SR-D NRK clones began segregating typical ASV-transformed cells. Transforming ASV could be rescued by fusion with chicken embryo fibroblasts from most of the infected clones tested. Three predominantly flat, independently infected clones were further analyzed by subcloning 8 to 10 weeks after infection. Most flat progeny subclones derived at random from two of these "parental" SR-D NRK clonal lines did not yield virus upon fusion with chicken embryo fibroblasts, although a nondefective transforming ASV was repeatedly recovered from the parental clones. This observation suggested that most, but not all, daughter cells in these SR-D NRK clones lost the ASV provirus after cloning. The progeny of the third independent parental cell clone, c17, gave rise to both flat and transformed subclones that carried ASV. In this case, ASV recovery by fusion and transfection from the progeny subclones was equally efficient regardless of the transformation phenotype of the cells. The 60,000-dalton phosphoprotein product of the ASV src gene was, however, expressed at high level only in the transformed variants. The results of a Luria-Delbruck fluctuation analysis and of Newcombe's respreading test indicated that the event leading to the spontaneous conversion to the transformed state occurred at random in dividing cultures of these flat ASV NRK cells at a rate predicted for somatic mutation. PMID- 6255186 TI - Polyoma virus middle t antigen: a tumor progression factor. AB - Polyoma virus (PyV) deletion mutant dl23 (affecting both large T and middle t but not small t antigens) was used to study transformation of 3T3 rat cells. This mutant generated stable transformants in the agar assay at a frequency similar to that of wild-type virus (WT). However, WT-induced transformants were detected 3 weeks after infection, whereas those induced by the mutant could not be detected until 6 to 8 weeks after infection. In this respect, dl23 PyV behaved like WT simian virus 40 (SV40). Cells transformed by WT SV40 or by dl23 PyV were similar in all their transformed properties. Those transformed by WT PyV were different from the others on the basis of morphology, cell adhesion to the substrate, release of protease activity, efficiency of doubling in agar, growth rate, and time required for tumor formation. Saturation density, the ability to grow in agar, the serum requirement for cloning, and the ability to grow on a cell monolayer were similar for all transformants. Middle t antigen enhanced membrane alterations and growth rate of the transformed cells, shortening the time required for tumor formation in rats. PMID- 6255188 TI - Characterization of JC papovavirus adapted to growth in human embryonic kidney cells. AB - Human papovavirus JC virus was adapted to growth in human embryonic kidney (HEK) cells. After eight passages, the HEK-adapted JC virus produced high virus yields and was capable of forming plaques in HEK monolayer cultures. Eleven plaque purified stocks were prepared and characterized. Biologically, the plaque purified virus induced tumor and viral antigens in HEK cells earlier and in a higher percentage of cells than uncloned virus. Cytopathic changes were also evident sooner and were more extensive. The DNA from uncloned as well as plaque purified isolates was analyzed by restriction endonuclease cleavage followed by gel electrophoresis. The DNA from uncloned HEK-adapted virus was heterogeneous. Plaque-purified virus isolates yielded DNA which, although much less heterogeneous than the uncloned stock, still consisted of two or more species of viral DNA. PMID- 6255187 TI - Frequent site-specific deletion of coliphage lambda murine sarcoma virus recombinants and its use in the identification of a retrovirus integration site. AB - Stocks of hybrid lambda phages carrying the complete integrated provirus of either m1 or HT1 Moloney murine sarcoma virus, as well as flanking host sequences, frequently contain significant numbers of phages carrying a specific deletion. This deletion arises from a recombination event between the terminally repeated sequences in the provirus that deletes the unique Moloney murine sarcoma virus sequences bracketed by the terminally repeated sequences. Physical mapping has shown that the deletion phage retains one complete copy of the terminally repeated sequence and the flanking mink host sequences. One such deletion, lambdaHT1r+, was used to characterize a mink genomic DNA sequence that contains an HT1 Moloney murine sarcoma virus integration site. This integration site sequence from normal mink cells was also cloned into phage lambda. An analysis of the heteroduplexes between the integration site and the lambdaHT1r+ deletion indicated that no major rearrangement of host sequences occurred upon integration of the Moloney murine sarcoma provirus. PMID- 6255189 TI - Simian virus 40 T-antigen-related cell surface antigen: serological demonstration on simian virus 40-transformed monolayer cells in situ. AB - Simian virus 40 (SV40)-transformed monolayer cells were analyzed in situ by indirect immunofluorescence microscopy for the postulated cell surface location of SV40 T-antigen-related molecules. With antisera prepared against purified, sodium dodecyl sulfate-denatured SV40 T-antigen, positive surface staining was obtained when the cells had been treated with formaldehyde before immunofluorescence analysis. In contrast, living SV40-transformed cells analyzed in monolayer were surface fluorescence negative. The fixation procedure developed in this study combined with a double staining immunofluorescence technique allowed the simultaneous analysis of the same cells for the expression of both SV40 T-antigen-related surface antigen and nuclear T-antigen. The localization of SV40 T-antigen-related surface antigen on the outer surface of the plasma membrane of formaldehyde-fixed SV40-transformed cells was demonstrated directly by the protein A-mediated binding of Staphylococcus aureus bacteria on formaldehyde-fixed SV40-transformed cells precoated with antiserum against sodium dodecyl sulfate-denatured T-antigen. Both cell surface staining and S. aureus binding were found to be highly specific for SV40 T-antigen-related binding sites. These results indicate that T-antigen-related molecules in a cryptic form are located on the surface of SV40-transformed monolayer cells and can be detected in situ after modification of the cell surface architecture. PMID- 6255190 TI - Stimulation of growth rate of chondrocytes by Rous sarcoma virus is not coordinated with other expressions of the src gene phenotype. AB - Infection and transformation of chondrocytes by Rous sarcoma viruses (RSVs) (Schmidt-Ruppin, Prague) stimulated the rate of cell growth. In contrast, several transformation-defective (td) mutants (tdPRA, tdNY105, tdNY106, tdNY107, and tdNY108) retaining various sizes of the src gene did not stimulate cell growth, indicating that the stimulation of growth of chondrocytes is due to the function of the src gene. With the use of various T (transformation)-class temperature sensitive (ts) mutants of RSV, growth stimulation of chondrocytes by the src gene was examined. It was found that there are two types of T-class ts mutants with regard to the stimulatory effect on the growth of chondrocytes. One type (tsNY68) stimulates cell growth at both permissive (36 degrees C) and nonpermissive (41.5 degrees C) temperature, as does the wild type of RSV. Another type (ts GI201 [clone 9]) stimulates cell growth only at the permissive temperature. Chondrocytes infected with either of these two types of T-class ts mutants showed ts properties in other transformation markers, such as uptake of 2-deoxy-D glucose, change of cell morphology, and focus formation. These data indicate that the effect of the src gene on cell growth does not occur coordinately with other transformation markers. PMID- 6255191 TI - Comparative analysis of the genomes of feline leukemia viruses. AB - The genomes of several strains of feline leukemia virus (FeLV) were compared by two-dimensional polyacrylamide gel electrophoresis of the large RNase T1 resistant oligonucleotides of the 70S RNA. Differences between each strain of FeLV tested were detected by this method. We estimate that the degree of sequence identity between the viruses is: FeLV A (Glasgow-1) to FeLV B (Snyder-Theilen), 52%; FeLV A (Glasgow-1) to FeLV C(Sarma), 66%; FeLV B(Snyder-Theilen) to FeLV C (Sarma), 37%. The fingerprints of two independent isolates of FeLV strains of subgroup A (Glasgow-1 and Rickard) were detectably different. We conclude that the RNase T1 oligonucleotide fingerprint pattern provides a useful tool for identification of FeLV strains. PMID- 6255192 TI - Antibody-resistant spread of vesicular stomatitis virus infection in cell lines of epithelial origin. AB - In MDCK cells, vesicular stomatitis virus (VSV) buds exclusively from the basolateral plasma membranes beneath tight junctions, whereas influenza virus forms only at the free apical surface. Anti-VSV antiserum did not prevent the formation of plaques on MDCK cell monolayers infected with VSV, whereas plaque formation in BHK-21 cells was completely inhibited by such antiserum. Under similar conditions, homologous antiserum completely prevented plaque formation by influenza virus on MDCK cells. In several other epithelioid cell lines, VSV also formed plaques in the presence of specific antiserum. These results suggest that VSV receptors are present on basolateral membranes in the cells studied and that junctional complexes present between cells may exclude antibody from intercellular spaces and thus permit the lateral spread of virus infection in the presence of neutralizing antibody. PMID- 6255194 TI - Transcripts of the adenovirus-associated virus genome: multiple polyadenylated RNAs including a potential primary transcript. AB - Adenovirus-associated virus type 2 synthesizes four prominent viral transcripts, containing 4.3, 3.6, 2.6, and 2.3 kilobases (kb), in productively infected human KB cells (coinfected with adenovirus type 2). All species are polyadenylated and present in both nuclear and whole-cell RNA preparations, but only the predominant 2.3-kb (and possibly the 2.6-kb) RNA species are found on polysomes. Electrophoretic analyses under denaturing conditions of S1 nuclease-generated and exonuclease VII-generated DNA-RNA hybrids revealed, in each case, four protected DNA fragments which are equal in length (within 50 to 100 nucleotides) to the four S1 nuclease-generated hybrids resolved by electrophoresis under nondenaturing conditions. These results suggest that in the infected cell, abundant adenovirus-associated virus type 2 transcripts are present predominantly (by mass) as unspliced RNAs or, alternatively, they are spliced but contain very short (less than or equal to 50 nucleotides) leader sequences. That the 2.3-kb RNA represents such a spliced transcript is suggested by exonuclease VII mapping experiments and our more detailed RNA mapping studies (M. R. Green and R. G. Roeder, J. Virol., in press). PMID- 6255193 TI - Bacteriophage T4-related macromolecular synthesis under restriction of plasmid Rts1. AB - Rts1 is a plasmid which confers upon the host bacteria the capacity to restrict T4 bacteriophage growth at 32 degrees C but not at 42 degrees C. Pulse-labeling of phage-infected cells showed that Rts1 restricts the synthesis of T1 DNA. Despite efficient restriction of T4 phage growth and DNA synthesis, infected Escherichia coli 20SO harboring Rts1 synthesized both early and late T4 phage RNA. Synthesis of early T4 phage RNA under restrictive conditions (32 degrees C) was almost equal to that found under nonrestrictive conditions, and a lesser, but significant, amount of late T4 phage RNA was made in almost complete absence of T4 DNA synthesis. Moreover, very little, if any, T4 phage-coded lysozyme was detected in the infected E. coli 20SO/Rts1 at 32 degrees C, whereas normal amounts of lysozyme were present at 42 degrees C. PMID- 6255195 TI - Stimulation of encephalomyocarditis virus RNA translation in wheat embryo extracts by rabbit reticulocyte ribosomal wash. AB - Encephalomyocarditis virus RNA induced a low level of amino acid incorporation in wheat embryo extracts, but the incorporation did not result in the formation of any viral proteins. However, if wheat embryo extracts were supplemented with a ribosomal wash fraction from rabbit reticulocytes, a large stimulation of amino acid incorporation and the formation of encephalomyocarditis virus-specific proteins were obtained. Among the proteins synthesized were capsid precursor proteins which can be processed by an encephalomyocarditis virus-coded protease to produce the viral capsid proteins. PMID- 6255196 TI - Iodination of hepatitis A virus reveals a fourth structural polypeptide. AB - Hepatitis A virus present in the feces of two patients with naturally acquired hepatitis A was purified, radiolabeled with 125I, and analyzed by discontinuous sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In addition to the three structural polypeptides previously reported, a fourth polypeptide with a molecular weight of 14,000 was detected and shown to be a component of hepatitis A virus by immune precipitation techniques. Intact virions were also shown to sediment at 160S on sucrose gradients. These findings are consistent with hepatitis A virus being an enterovirus within the family Picornaviridae. PMID- 6255197 TI - Use of vesicular stomatitis virus pseudotypes to map viral receptor genes: Assignment of RD114 virus receptor gene to human chromosome 19. AB - Vesicular stomatitis virus pseudotypes bearing envelope glycoproteins of the endogenous feline type C retrovirus, RD114, were used to assay the expression of receptors specific to RD114 on the surfaces of mouse-human hybrid cells carrying different human chromosomes. These studies show that the gene encoding the RD114 receptor is located on human chromosome 19. PMID- 6255198 TI - Correlation between genetic map and map of cleavage sites for sequence-specific endonucleases SalI, KpnI, BglI, and BamHI in bacteriophage T4 cytosine-containing DNA. AB - Cleavage sites for SalI, KpnI, BglI, and BamHI in cytosine-containing DNA from T4 alc10(alc) nd28(denA) D2a2(denB) amE51x5(56) amN55x5(42) have been mapped relative to each other, and the positions of deletions sa delta 9 (D1-stp), r1589(rII), del(39-56)12, and tk2(rI-tk) relative to these cleavage sites have been determined. Based on these analyses, a physical map of the T4 genome containing 166 kilobase pairs has been constructed. PMID- 6255199 TI - Selective amplification of mouse mammary tumor virus in mammary tumors of GR mice. AB - DNAs extracted from the mammary tumors of GR mice were analyzed for mouse mammary tumor virus proviral sequences by the restriction enzyme-Southern blot procedure. The tumor DNAs contain more proviral copies of mouse mammary tumor virus than DNA from a nonmalignant tissue. The degree of proviral amplification is small (ca. one to five additional copies) and appears to be variable from tumor to tumor. The restriction patterns of the amplified proviral sequences suggest a clonal origin for the tumor mass. In addition, the restriction patterns observed after digestion with the enzymes BglII and SacI indicate that only one of the proviruses endogenous to GR mice is amplified. The amplified provirus found in GR mammary tumors is identical to the provirus that is missing in GR-Mtv-2- mice, a congenic line exhibiting a low mammary tumor incidence. PMID- 6255200 TI - Expression of the gene for the polyoma small T antigen in Escherichia coli. AB - A cloned segment of the polyoma virus genome encoding the small T antigen has been fused, in the correct phase for translation, to the 5' end of the beta galactosidase gene. The hybrid gene, cloned in Escherichia coli, produces a protein resembling the small T antigen. PMID- 6255201 TI - New chimeric splice junction in adenovirus type 2-simian virus 40 hybrid viral mRNA. AB - We have examined hybrid viral RNAs synthesized in both human and monkey cells infected by three nondefective adenovirus type 2 (Ad2)-simian virus 40 (SV40) hybrid viruses; Ad2+ND1, Ad2+ND2, and Ad2+ND4. Most of the hybrid viral RNA molecules appeared to be initiated within adenoviral sequences, but were polyadenylated on their 3' end at the early SV40 mRNA polyadenylation site. The Ad2+ND4 stock of virus was not homogeneous, but consisted of two principle populations of viral DNA. Both populations contained a segment of SV40 DNA extending from the SV40 map positions 0.63 to 0.11 in a left-to-right orientation at adenovirus map position 0.82. One population contained an intact SV40 segment, whereas the other (representing 80 to 85% of the population) has a 500-base pair deletion mapping from approximately 0.60 to 0.50 SV40 map units. This deletion encompassed the SV40 DNA segment which encodes the early SV40 splice sites. Cells infected by the mixed Ad2+ND4 population induced the synthesis of at least three major SV40 RNA species among the hybrid viral transcripts. The most abundant of these hybrid mRNA's appeared only late in the lytic cycle, after the onset of viral DNA replication. It contained an RNA splice junction which extended from a donor (5') nucleotide within the adenoviral RNA sequences to an acceptor (3') splice site within the early region of SV40 at 0.46 SV40 map units. This SV40 acceptor splice site was remarkable in that its use has not been detected in the spliced viral mRNA's of SV40-infected or -transformed cells. PMID- 6255202 TI - DNA nucleotide sequence heterogeneity between the Towne and AD169 strains of cytomegalovirus. AB - The results of reciprocal DNA-DNA reassociation kinetics indicated that although the DNAs of human cytomegalovirus (CMV) strains Towne and AD169 shared approximately 90% of their nucleotide sequences, about 10% heterogeneity did exist. The implication was that, with respect to one another, the DNAs of CMV Towne and CMV AD169 contained unique nucleotide sequences. To obtain more direct evidence, 32P-labeled DNA of one virus strain was reassociated in the presence of excess unlabeled DNA of the heterologous virus strain. Those 32P-labeled DNA sequences remaining single stranded were separated from double-stranded DNA on hydroxyapatite columns and incubated with Southern blots containing XbaI restriction enzyme fragments of the homologous virus DNA. This approach not only enriched for nucleotide sequences unique to each strain of virus, but also provided for the identification of the restriction enzyme fragments in which the unique sequences were contained. The CMV Towne unique sequences were found in XbaI fragments A, C, G, L, N, and Q of CMV Towne DNA. The CMV AD169 unique sequences were found in XbaI fragments A, C, G, and J of CMV AD169 DNA. The possible significance of these data with respect to variation among other CMV isolates is discussed. PMID- 6255203 TI - Expression of endogenous avian myeloblastosis virus information in different chicken cells. AB - Uninfected chicken cells were found to contain endogenous avian myeloblastosis virus (AMV)-specific information. Different tissues from chicken embryos and chickens expressed different amounts of the AMV-specific information. The endogenous AMV-related RNA was most abundant in bone marrow cells, which contained about 20 copies per cell. About 5 to 10 copies of AMV endogenous RNA per cell were found in embryonic yolk sac cells and bursa cells. The spleen, muscle, liver, and kidney cells of chickens and the fibroblasts of chicken embryos contained about two copies per cell. The amounts of AMV endogenous RNA in bone marrow, yolk sac, and bursa varied with age. From 19-day-old embryos to 2 week-old chickens, the bone marrow contained 20 copies of AMV RNA per cell. Bone marrow cells from 2-year-old chickens contained five copies per cell. Yolk sac cells of 10-day-old embryos and 1-day-old chickens were found to contain two copies per cell, whereas in 15- to 17-day-old embryos, these cells contained 5 to 10 copies. These results indicate that the level of endogenous AMV expression correlates with the development of granulopoiesis of the chicken hemopoietic system. The results of experiments on the thermostability of RNA-DNA hybrids indicated that the endogenous AMV RNA is closely related to viral AMV RNA. The expression of endogenous AMV information is independent of the activity of the chick helper factor. This endogenous AMV information is expressed as 20 to 21S RNA in both bone marrow and yolk sac cells. PMID- 6255204 TI - Lack of focus formation of S+L- mink cells by the ecotropic murine leukemia viral genome. AB - Infection of mink S+L- cells with ecotropic murine leukemia virus, achieved by phenotypic mixing with xenotropic virus, did not result in the induction of transformed foci. Also, clonal line of S+L- mink cells, chronically infected with ecotropic murine leukemia virus, which produce both the ecotropic virus and its murine sarcoma virus pseudotype are morphologically indistinguishable from normal S+L- mink cells. Neutralizing antiserum added to S+L- mink cells inoculated with xenotropic virus 24 h earlier prevented the formation of foci of transformed cells. Together, these observations indicate that focus formation in S+L- cells requires a regional spread of infection, with the insertion of additional murine sarcoma virus genomes and resultant transformation occurring from a gene dosage effect. PMID- 6255205 TI - Covalently closed circular DNAs of murine type C retrovirus: depressed formation in cells treated with cycloheximide early after infection. AB - Formation of viral closed circular supercoiled DNA duplexes and production of progeny virus were both inhibited in cultured mouse cells treated with cycloheximide in the first 4 h of type C retrovirus infection. With different doses of cycloheximide to cause different degrees of inhibition, the number of viral supercoiled DNA duplexes detected in the cells at 11 h showed an apparent correlation with the amount of progeny virus produced in the 12- to 22-h period of infection. A slight accumulation of the full-genome linear duplex and an open circular duplex of viral DNA intermediate was observed in the cycloheximide treated cells. Cycloheximide given to the cells during the time of conversion of viral DNA from linear to supercoiled duplex forms (6 to 11 h after virus inoculation) did not inhibit the conversion. These kinetic data suggest that a cycloheximide-sensitive metabolic process, probably early viral protein synthesis, is required for retrovirus replication and supercoiled viral DNA formation in the cell. PMID- 6255206 TI - Fine-structure mapping and functional analysis of temperature-sensitive mutants in the gene encoding the herpes simplex virus type 1 immediate early protein VP175. AB - Herpes simplex virus (HSV)-specific proteins fall into at least three kinetic classes whose synthesis is sequentially and coordinaely regulated. Temperature sensitive (ts) mutants of one complementation group (1-2) are defective in the transition from immediate early to early and late protein synthesis. To elucidate the function of the 1-2 gene product in the HSV type 1 replicative cycle, nine ts mutants in this group were mapped by fine-structure analysis and characterized members of the group lie within the terminally repeated sequences of the S region of the genome. Fine-structure genetic and physical mapping permitted the mutations to be ordered within these sequences. Because it has been shown that the message for VP175 and the DNA template specifying this protein extend beyond the limits of the physical map of the mutations, it follows that the mutations must lie within the structural gene for VP175. Sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis showed that most members of the group overproduced the immediate early proteins VP175, -136, -110, and -63 and markedly underproduced early and late proteins at the nonpermissive temperature. In temperature shiftup experiments, it was fund that the synthesis of early and late proteins ceased, whereas the synthesis of immediate early proteins began again. Thus, it is postulated that VP175 is (i) involved in the transition from immediate early to early protein synthesis, (ii) requird continuously to maintain early protein synthesis, (iii) autoregulated, acting to inhibit immediate early protein synthesis. PMID- 6255207 TI - Oncogenic transformation by by equine herpesviruses. II. Coestablishment of persistent infection and oncogenic transformation of hamster embryo cells by equine herpesvirus type 1 preparations enriched for defective interfering particles. AB - Infection of permissive hamster embryo cells with virus preparations enriched for defective interfering (DI) particles of equine herpesvirus type 1 (EHV-1) resulted in persistent infection and oncogenic transformation. Six cell lines, designated DI-5 to -10, exhibited biological properties (immortality, increased saturation density, growth in soft agar, etc.) inherent to transformed cells, but 2 to 18% of the total cells in these cell lines were shown to release virus as judged by electron microscope studies and infectious center assays. The released virus was shown to be standard EHV-1 and not to contain DI particles as determined by density measurements of the viral DNA in the analytical ultracentrifuge and by interference assays using the released virus. Tumorigenicity studies revealed that inoculation of these persistently infected cells into newborn LSH inbred hamsters resulted in a lethal, fulminating hepatitis, whereas inoculation into older immunocompetent hamsters (+4 weeks) led to the development of metastatic fibrous sarcomas. Tumor cell lines (DI-5T to 10T) established from these sarcomas were shown to be transplantable and virus nonproducers. Hybridization analyses of cellular DNAs from DI transformed and tumor cell lines using 32P-labeled genomic EHV-1 DNA as probes indicated that the whole virus genome was detectable in multiple copies (23 to 45) in the transformed cells and that DNA sequences representing only 43.5 to 56.6% of the virus genome were present in amounts of 2 to 4 copies per cell in the DI tumor cells. Expression of these viral DNA sequences as demonstrated by the detection of virus-neutralizing antibodies, 50% neutralizing dose titers ranging from 1:50 to 1:1,000, in the sera of animals inoculated with either the virus-producing transformed cells or the virus-nonproducing tumor cells. Further, EHV-1-specific proteins were detected in the membrane and the perinuclear region of bothDI transformed and tumor cells by indirect immunofluorescent assays using antisera against EHV-1 structural antigens, EHV-1 nonstructural antigens, or preparations of EHV-1 DI particles. The roles of DI particles in mediating persistent infection and cellular transformation are discussed. PMID- 6255208 TI - Anogenital warts contain several distinct species of human papillomavirus. AB - Anogenital warts from 26 patients were examined for the presence of human papillomavirus (HPV). Although no whole, intact virus could be identified, varying amounts of nonintegrated HPV DNA were detected in 18 tissue specimens (70%) by employing both an agarose gel-ethidium bromide staining method and the Southern blot hybridization procedure. When hybridization analysis was performed under stringent conditions, six anogenital warts were observed to contain HPV genomic sequences related to either of the cutaneous viruses HPV type 1 (HPV-1) or HPV-2. In 12 tissue samples lacking sequence homology to either HPV-1 or HPV-2 under stringent conditions, HPV-related sequences were detected when the hybridization was performed under less stringent conditions, indicating that an HPV distinct from both HPV-1 and HPV-2 is also associated with these lesions. This anogenital HPV also appeared to be distinct from the other characterized types of HPV. These data indicate that at least three HPVs are associated with anogenital wart disease. PMID- 6255209 TI - New endogenous herpesvirus of guinea pigs: biological and molecular characterization. AB - Two known guinea pig herpesviruses, guinea pig cytomegalovirus (GPCMV) and guinea pig herpes-like virus (GPHLV), and well characterized. A third herpesvirus (GPXV) was originally isolated from leukocytes of healthy strain 2 guinea pigs. Growth of GPXV in guinea pig embryo fibroblastic cells produced a characteristic cytopathic effect. Electron microscopy of guinea pig cells infected with GPXV revealed the morphological development of a herpesvirus. Cross-neutralization tests and immunoferritin electron microscopy demonstrated that GPXV, GPCMV, and GPHLV were serologically distinct herpeviruses of guinea pigs. To confirm the distinction between these three herpesviruses, DNA genomes were compared by CsCl equilibrium buoyant density measurements and restriction endonuclease cleavage analysis. 32P-labeled viral DNA ws obtained from nucleocapsids isolated from virus-infected cells, and the buoyant density of GPXV DNA differed from that of GPCMV and GPHLV. Cleavage of viral DNAs with restriction endonucleases followed by gel electrophoresis revealed distinct patterns for each virus. PMID- 6255210 TI - Molecular cloning of unintegrated and a portion of integrated moloney murine leukemia viral DNA in bacteriophage lambda. AB - A covalently closed circular form of unintegrated viral DNA obtained from NIH 3T3 cells freshly infected with Moloney murine leukemia virus (M-MLV) and a port of the endogenous M-MLV from the BALB/Mo mouse strain have been cloned in bacteriophage lambda. The unintegrated viral DNA was cleaved with restriction endonuclease HindIII and inserted into the single HindIII site of lambda phage Charon 21A. Similarly high-molecular-weight DNA from BALB/Mo mice ws cleaved sequentially with restriction endonucleases EcoRI and HindIII and separated on the basis of size, and one of the two fractions which reacted with an M-MLV specific complementary DNA was inserted into the HindIII site of Charon 21A. Recombinant clones containing M-MLV-reacting DNA were analyzed by restriction endonuclease mapping, heteroduplexing, and infectivity assays. The restriction endonuclease map of the insert derived from unintegrated viral DNA, lambda x MLV 1, was comparable to published maps. Electron microscope analysis of the hybrid formed between lambda x MLV-1 DNA and 35S genomic M-MLV RNA showed a duplex structure. The molecularly cloned lambda x MLV-1 DNA contained only one copy of the long terminal repeat and was not infectious even after end-to-end ligation of the insert DNA. The insert DNA derived from endogenous M-MLV, lambda x MLVint-1, contained a DNA stretch measuring 5.4 kilobase pairs in length, corresponding to the 5' part of the genomic viral RNA, and cellular mouse DNA sequences measuring 3.5 kilobase pairs in length. The viral part of the insert showed the typical restriction pattern of M-MLV DNA except that a single restriction site, PvuII, in the 5' long terminal repeat was missing. Reconstructed genomes containing the 5' half derived from the integrated viral DNA and the 3' half derived from the unintegrated viral DNA were able to induce XC plaques after transfection in uninfected mouse fibroblasts. PMID- 6255211 TI - Molecular cloning of avian sarcoma virus closed circular DNA: structural and biological characterization of three recombinant clones. AB - Unintegrated, circular viral DNA, isolated from Prague A avian sarcoma virus (PrA ASV)-infected quail cells (QT6), was cloned in the lambda vector lambda gtWES x lambda B. Three independent lambda-ASV recombinants were identified, and each contained a complete copy of the PrA-ASV genome. The arrangement of the ASV sequences within the recombinants was determined by restriction enzyme analysis and hybridization with labeled ASV-specific complementary DNA. One of the recombinants (lambda RPA101) resulted from cloning at the EcoRI site located within the terminally repeated sequence and therefore was virtually co-linear with PrA-ASV virion RNA. The other two recombinants (lambda RPA102 and 103) resulted from cloning at the EcoRI site located within the viral env gene. By restriction enzyme analysis and by measurement of R-loops formed between lambda RPA101 and PrA-ASV virion 35S RNA, the viral genome was estimated to be 9,100 bases in length. Genome length viral DNA purified from clones lambda RPA102 and 103 was biologically active. Transfection of chicken embryo cells with viral DNA, in the form of either circles or linear dimers, produced foci of transformed cells within 8 to 10 days. Linear DNA was much less efficient at inducing transformation. Viral DNA from the clone lambda RPA101 was unable to cause transformation; the basis for this defect is unknown. PMID- 6255212 TI - Synthesis and processing of viral glycoproteins in two nonconditional mutants of Rous sarcoma virus. AB - We have studied the pattern of glycoprotein synthesis in two nonconditional mutants of Rous sarcoma virus. One mutant, SE33, produces no viral particles but synthesizes Pr92env, which is cleaved intracellularly to mature glycoproteins. The second mutant, SE521, encodes a gPr92env which is not cleaved to gp85 or gp37 and therefore produces virions with the phenotype of Bryan RSV(-) or NY8. Neither of these mutants have detectable genomic deletions. The study of these mutants has led to the following conclusions. (i) In the absence of particle production or p15 synthesis, gPr92env can be cleaved to the mature glycoprotein which is found on the cell surface. (ii) Noncleaved gPr92env is not packaged into virions but is found on the cell surface. (iii) gPr92env alone can account for subgroup specific viral interference. (iv) gPr92env is probably transported to the cell surface before additional glycosylation or cleavage to mature virion glycoprotein. The nonprocessed precursor of SE521 appears to be glycosylated normally, and thus far we have been unable to determine the basis for the defect in this mutant. PMID- 6255213 TI - Simian virus 40-Chinese hamster kidney cell interaction. V. Cooperative effect of 5-iodo-2'-deoxyuridine and mitomycin C in the enhancement of virus replication in infected cells. AB - A cooperative effect of 5-iodo-2'-deoxyuridine and mitomycin C which amplified (10- to 50-fold) their stimulating effect on simian virus 40 replication was obtained in infected Chinese hamster kidney cells. The results indicate that these drugs act at different levels to modify the permissiveness of cells to simian virus 40. PMID- 6255214 TI - Molecular cloning and characterization of avian sarcoma virus circular DNA molecules. AB - Supercoiled DNA molecules were used for the molecular cloning of full-length avian sarcoma virus (ASV) DNA. Viral DNA produced by the Schmidt-Ruppin A (SR-A) strain of ASV was isolated from acutely infected transformed quail cells. Supercoiled DNA was separated from linear and open circular DNA by acid phenol extraction, opened into a full-length linear form by cleavage with the restriction endonuclease SacI, and cloned into lambda gtWES x lambda B. Four different cloned viral DNA molecules were isolated: SRA-1 contains two copies of the 330-base pair terminal redundancy normally found at each end of the linear DNA molecules, but harbors a 63-base pair deletion that spans the site at which the two copies of the terminal redundancy are joined in circular DNA molecules; SRA-2 contains two complete copies of the terminal redundancy; SRA-3 probably contains only one copy of the terminal redundancy but in all other respects appears to be similar to SRA-2; SRA-4 contains a 2,500-base pair deletion that removes all of the src gene (the gene responsible for transformation by ASVs) plus additional nucleotides adjacent to the src gene whose precise locations have not been determined. Transfection of chicken embryo fibroblasts by either SRA-1 or SRA-2 resulted both in the appearance of transformed cells and in the production of infectious virus. These results demonstrate that the cloned DNA molecules are functionally identical to viral DNA produced in vivo; therefore, molecular cloning did not cause any major alterations of the DNA. The infectivity of SRA-1 DNA indicates that the 63 base pairs missing from that molecule are not required for the initiation of viral RNA synthesis, even though the deletion is located in a copy of the terminal redundancy thought to carry a promoter for RNA synthesis. This suggests that the deletion does not remove any sequences required for the initiation of transcription. PMID- 6255216 TI - Localization of membrane-associated proteins in vesicular stomatitis virus by use of hydrophobic membrane probes and cross-linking reagents. AB - The location of membrane-associated proteins of vesicular stomatitis virus was investigated by using two monofunctional and three bifunctional probes that differ in the degree to which they partition into membranes and in their specific group reactivity. Two hydrophobic aryl azide probes, [(125)I]5-iodonaphthyl-1 azide and [(3)H]pyrenesulfonylazide, readily partitioned into virion membrane and, when activated to nitrenes by UV irradiation, formed stable covalent adducts to membrane constituents. Both of these monofunctional probes labeled the glyco protein G and matrix M proteins, but [(125)I]5-iodonaphthyl-1-azide also labeled the nucleocapsid N protein and an unidentified low-molecular-weight component. Protein labeling of intact virions was unaffected by the presence of cytochrome c or glutathione, but disruption of membrane by sodium dodecyl sulfate greatly enhanced the labeling of all viral proteins except G. Labeling of G protein was essentially restricted to the membrane-embedded, thermolysin-resistant tail fragment. Three bifunctional reagents, tartryl diazide, dimethylsuberimidate, and 4,4'-dithiobisphenylazide, were tested for their capacity to cross-link proteins to membrane phospholipids of virions grown in the presence of [(3)H]palmitate. Only G and M proteins of intact virions were labeled with (3)H-phospholipid by these cross-linkers; the reactions were not affected by cytochrome c but were abolished by disruption of virus with sodium dodecyl sulfate. Dimethylsuberimidate, which reacts with free amino groups, cross-linked (3)H phospholipid to both G and M protein. In contrast, the hydrophilic tartryl diazide cross-linked phospholipid primarily to the M protein, whereas the hydrophobic 4,4'-dithiobisphenylazide cross-linked phospholipid primarily to the intrinsic G protein. These data support the hypothesis that the G protein traverses the virion membrane and that the M protein is membrane associated but does not penetrate very deeply, if at all. PMID- 6255218 TI - Studies on sacral-evoked potentials. AB - The bulbocavernosus reflex may be evoked electrically with a latency of approximately 35 msec. in normal male subjects. We have studied the sacral-evoked response in 116 individuals, 10 of whom were normal controls. For each study ipsilateral and contralateral responses were obtained from each side, resulting in 4 latency values. We herein describe the abnormalities in 54 patients with a variety of documented neurologic lesions. Our investigation reveals that the bulbocavernosus reflex has the characteristics of a cutaneous polysynaptic bilateral flexor response. The use of bilateral stimulation and recording techniques permits more effective localization of neurologic lesions involving the conus medullaris or cauda equina roots. PMID- 6255217 TI - Beta-adrenergic activity in human proximal urethra: a study with terbutaline. AB - Beta-adrenergic activity in the proximal urethra was studied in 15 patients with neurogenic bladder dysfunction owing to spinal cord injury or to neurogenic disease. Maximum urethral closure pressure was recorded before and after the administration of terbutaline, a beta-2 agonist. The average decrease in maximum urethral closure pressure after subcutaneous injection of terbutaline was 40.46 per cent and this was significant (p less than 0.001). The clinical implications of this finding are discussed. PMID- 6255215 TI - Transcripts of the adeno-associated virus genome: mapping of the major RNAs. AB - The four major adeno-associated virus type 2 (AAV2)-specific RNAs were mapped on the linear viral genome by a variety of biochemical techniques, including S1 nuclease and exonuclease VII mapping, RNA gel-transfer hybridization, and analysis of reverse transcriptase extension products. All the major AAV2 RNAs were derived from the minus DNA strand and had 3' termini at position 96. The nucleus-specific 4.3- and 3.6-kilobase (kb) RNAs had 5' termini at positions 6 and 19, respectively. The 5' terminus of the 2.6-kb RNA mapped to position 38.5. The predominant 2.3-kb AAV2 mRNA was spliced and contained a short leader sequence (approximately 50 nucleotides) which mapped to position 38.5, coincident with the 5' terminus of the 2.6-kb RNA. The 5' end of the body of the 2.3-kb RNA mapped to position 46.5. These results are discussed in terms of the involvement of single versus multiple promoters (for transcription) and RNA splicing mechanisms in the generation of the AAV2 RNAs. PMID- 6255219 TI - Comparison of cardiac lesions induced in rats by isoproterenol and by repeated stress of restraint and water immersion with special reference to etiology of cardiomyopathy. AB - Cardiac lesions induced in rats by isoproterenol, a potent beta-agonist, and by repeated stress of restraint and water immersion, in which sensitization of beta adrenergic receptors would be expected to be induced, were investigated morphologically and following facts were revealed. 1) Cardiac lesions induced by isoproterenol, characteristic findings of which were myocardial hypertrophy, myocardial degeneration and myocardial necrosis replaced by interstitial fibrosis, were more analogous to cardiomyopathy than myocardial infarction or cardiac hypertrophy. 2) Cardiac lesions induced by repeated stress of restraint and water immersion, characteristic findings of which were myocardial hypertrophy, myocardial degeneration and myocardial necrosis replaced by interstitial fibrosis, were similar to those induced by isoproterenol. These results suggest that the endogenously induced dominant beta-adrenergic stimulating action during stress may play an important role in the pathogenesis of cardiomyopathy, the specific etiology of which is not yet known. PMID- 6255220 TI - [Cyclic AMP and cyclic GMP in ischemic myocardium and effect of propranolol on those nucleotides (author's transl)]. PMID- 6255221 TI - [Serological and clinical studies of sporadic acute viral hepatitis type A. Part 1. Serodiagnosis of sporadic acute viral hepatitis type A (author's transl)]. PMID- 6255222 TI - [Radioisotope methods of studying the foci of myocardial ischemia]. PMID- 6255223 TI - Control of vascular responsiveness during human pregnancy. AB - Normal human pregnancy is characterized by vascular refractoriness to AII. This pregnancy-induced vascular refractoriness appears to be mediated principally by decreased vascular smooth muscle responsiveness to AII rather than by alterations in blood volume or plasma concentrations of renin or AII. The mechanism that controls vascular refractoriness during normal pregnancy likely involves a localized prostaglandin or prostaglandin-like action mediated through cyclic nucleotides. The action of progesterone or one of its metabolites appears to mediate the synthesis or the catabolism of locally produced prostaglandins or prostaglandin-like agents. PMID- 6255224 TI - [Detection and registration of impulse conduction and its modification]. PMID- 6255225 TI - Renal responsiveness to parathyroid hormone in a case of nonfamilial hypophosphatemic osteomalacia. AB - Plasma immunoreactive parathyroid hormone level, urinary excretion of adenosine cyclic 3',5'-monophosphate (cyclic AMP) and the sensitivity of the renal tubule to calcium infusion and to parathyroid extract were investigated in a patient with nonfamilial hypophosphatemic osteomalacia. Plasma immunoreactive parathyroid hormone concentration was normal and basal urinary excretion of cyclic AMP was increased. Renal cortical adenylate cyclase, as measured by urinary cyclic AMP excretion, was certainly as sensitive to exogenous parathyroid extract as in normal subjects. After a previous calcium infusion, a greater parathyroid-hormone sensitive component of phosphorus transport in the kidney was present than in two control subjects. Our results indicate that in nonfamilial hypophosphatemic osteomalacia the renal tubule could be hyperresponsive to parathyroid hormone. PMID- 6255227 TI - [Problems in nursing]. PMID- 6255228 TI - [The patient from the viewpoint of community policy]. PMID- 6255229 TI - [Rooming-in. 4]. PMID- 6255226 TI - [Preadipocytes: a new model in obesity research (author's transl)]. AB - The present knowledge about the differentiation of preadipocytes into adipocytes is reviewed. The adipose conversion is initiated by an as yet unknown serum factor and is enhanced by various hormones including insulin, prostaglandin F2 alpha, steroids, and prolactin; prostaglandin E1 and phorbol diesters are inhibitors of differentiation. Adipose conversion of fibroblasts (preadipocytes) is associated with the coordinate induction of key enzymes of the lipogenetic and lipolytic pathways and is accompanied by profound changes in hormone responsiveness. Pathophysiological studies with preadipocytes of genetically obese mice show differences between adipocyte precursors of obese animals and lean controls which may be casually related to obesity. Regional differences in the hormonal regulation of fibroblast conversion might be important for the sex differences of fat deposition in human beings. PMID- 6255230 TI - [The patient and smoking]. PMID- 6255231 TI - [Research in nursing: study on the causes of urinary tract infections in patients with indwelling catheters]. PMID- 6255232 TI - [What will become of the nursing program in Europe?]. PMID- 6255233 TI - [Drugs as a means of nurse-patient relations. Theory and impact on the reality of the psychiatric hospital]. PMID- 6255234 TI - [Rooming-in. 3]. PMID- 6255235 TI - [Epidemiology and transcultural psychiatry of depression]. PMID- 6255236 TI - [Observations of a night nurse in the care of dying patient]. PMID- 6255237 TI - [Anniversary year of the Ingenbohler nurses. A look backward at celebrations and exhibits in the School of General Nursing of the Ingenbohl Institute in St. Clara Hospital, Basel]. PMID- 6255238 TI - [Swiss Placement Bureau for Foreign Nursing Personnel]. PMID- 6255239 TI - [Rooming-in]. PMID- 6255240 TI - [Problems in nursing]. PMID- 6255241 TI - [A Swiss nurse in Zaire: impressions at initial contact]. PMID- 6255242 TI - [Alcohol]. PMID- 6255243 TI - [Drug dependencies. II. Alcohol. Apropos of patients called "alcoholic" and of a practice in a center called "specific"]. PMID- 6255244 TI - [Polyvalent nurse in outpatient psychiatry. Observations of an experience in a specialized section]. PMID- 6255245 TI - [Youths and alcohol; by imitation and because of idleness]. PMID- 6255246 TI - [For women drinking means immediate degradation. A former "alcoholic" testifies in order to help others quit]. PMID- 6255247 TI - [The hospitalized alcohol and tobacco user: nursing care concerned. ENT: a service especially involved]. PMID- 6255248 TI - [Nursing care and supervision of alcoholics in the institutional environment]. PMID- 6255249 TI - [How research contributes to the understanding of nursing]. PMID- 6255250 TI - [Alcohol: psychiatric nursing report with notes over 5 days]. PMID- 6255251 TI - [Alcohol: Jellinek's alcoholic types]. PMID- 6255252 TI - [Alcohol: the bottle of red wine on the patient's bedside table]. PMID- 6255253 TI - [Medical research from the viewpoint of nursing services]. PMID- 6255255 TI - Induction of T cell-independent eosinophilia in mice with polymyxin B and schistosome infection. AB - This study examined the elevation of blood eosinophil counts in athymic and thymus-intact mice after repeated injections of polymyxin B with and without infection by Schistosoma mansoni. In athymic mice, a modest, comparable eosinophilia occurred after polymyxin B injection or parasite infection alone, or after a combination of both. In thymus-intact mice, polymyxin B injection caused a similar low grade eosinophilia, and schistosome infection produced a much higher level of eosinophilia. The combination resulted in the highest levels during the early weeks after infection; this hyperresponsive phenomenon was most apparent following 5 to 7 weekly polymyxin B injections, and the total eosinophil count approximated that derived by adding the eosinophil counts induced by polymyxin B injections or schistosome infection alone. In spite of the changes in blood eosinophil counts, tissue eosinophilia in the liver revealed no apparent differences. Furthermore, in schistosome-infected and polymyxin B-injected thymus intact mice, hepatic granulomas reached a maximal size earlier than in mice that were only infected, and there was an over-all reduction in mast cell counts. The findings indicate that a T cell-independent eosinophilia occurs under a variety of circumstances. In athymic mice, it accounts for all peripheral eosinophilia, whereas in thymus-intact mice, it operates independently from the well known T cell-dependent eosinophilia of parasite infections. PMID- 6255254 TI - The 4-methylumbelliferone sulphate sulphatases of human tears. AB - The properties of human tear 4-methylumbelliferone sulphate sulphatase (EC 3.1.6.1) have been investigated. More than 80% of the enzyme activity behaved as the acidic A isoenzyme on isoelectric focusing and DEAE-cellulose ion exchange chromatography. The distribution of enzyme activity in a normal population has been investigated. The least interindividual variation was seen when enzyme activities were calculated as units per mg tears. The alpha-galactosidase, beta-N acetylglucosaminidase and sulphatase enzyme activities in human tears varied independently of each other. The use of tear sulphatases for the detection of metachromatic leukodystrophy (McKusick 24980) is discussed. PMID- 6255256 TI - Conjugated and unconjugated plasma oestrogens--oestrone, oestradiol and oestriol- in normal human males. PMID- 6255257 TI - The scavenger cell pathway for lipoprotein degradation: specificity of the binding site that mediates the uptake of negatively-charged LDL by macrophages. AB - Macrophages isolated from a variety of organs in several animal species exhibit high affinity binding sites that recognize chemically modified proteins. One of these binding sites recognizes human plasma low density lipoprotein (LDL) in which the positive charges on the epsilon-amino groups of lysine have been removed or neutralized by chemical modification, thus giving the protein an enhanced negative charge. Effective treatments include reaction of LDL with organic acid anhydrides (acetylation or maleylation) and reaction with aldehydes, such as treatment with malondialdehyde. After the negatively-charged LDL binds to the surface receptor sites, it is rapidly internalized by the macrophages by endocytosis and hydrolyzed in lysosomes. The liberated cholesterol is reesterified in the cytoplasm, producing massive cholesteryl ester deposition. The binding sites for negatively-charged LDL has been demonstrated so far only on macrophages and other scavenger cells. It is not expressed in cultured fibroblasts, smooth muscle cells, lymphocytes, or adrenal cells. In addition to its affinity for acetylated LDL and malondialdehyde-treated LDL, the macrophage site binds a variety of polyanions. It exhibits a particularly high affinity for certain sulfated polysaccharides (dextran sulfate and fucoidin), certain polynucleotides (polyinosinic acid and polyguanylic acid), polyvinyl sulfate, and maleylated albumin. It is possible that the site that binds negatively-charged LDL may be responsible for the massive accumulation of cholesteryl esters that occurs in vivo in macrophages and other scavenger cells in patients with high levels of circulating plasma LDL. PMID- 6255258 TI - The role of hepatic artery ligation and dearterialization with infusion chemotherapy in advanced malignancies in the liver. AB - Because of limited benefits derived with the use of systemic chemotherapy, 15 patients with metastatic malignancy of the liver or hepatoma were treated by hepatic artery ligation (6) or dearterialization (9) and regional infusion chemotherapy. There were two postoperative deaths and three patients required surgical drainage of hepatic tumor liquefaction necrosis. The median survival was 14 months with two patients still living. The longest survivors were those patients with visceral leiomyosarcoma or carcinoid tumor. Five of the patients had failed to respond to previous chemotherapy, all showed a favorable response to this therapy. Rigid criteria for proper case selection have been developed which should reduce the operative mortality. Hepatic artery ligation is a therapeutic modality that can be of benefit to patients for whom no other satisfactory treatment is available. PMID- 6255259 TI - Estimation of ionic channel surface density from relaxation ionic and gating currents. PMID- 6255260 TI - Effects of isotope substitution on intermolecular electron transfer in biological systems. PMID- 6255261 TI - Insulin antagonism of dexamethasone-induced stimulation of cholinephosphate cytidylyltransferase in fetal rat lung in organ culture. PMID- 6255262 TI - Lymphoedema, macrophages and benzopyrones. AB - The role of macrophages in lymphoedema is discussed, with particular reference to post mastectomy lymphoedema. In the latter, the normal course of events is detailed using clinical and experimental evidence. Particular importance is placed on the events of the latent phase since it is during this time that important changes are occurring in the functioning of the blood-tissue-lymph system. These changes are not usually demonstrable clinically until the end of the latent phase when lymphoedema becomes manifest. Evidence suggests that the majority of these changes can be linked with changes in the functioning of the members of the mononuclear phagocytic system. Of particular importance is the disruption to the normal tissue remodelling processes as we know in lymphoedema the delicate balance between the deposition and lysis of collagenous fibres is shifted in favour of deposition--thus fibrosis occurs. The basic mechanisms behind such changes are discussed. A group of drugs, called the benzopyrones have been shown both clinically and experimentally to be of benefit in reducing most forms of high protein oedemas including lymphoedema. It is shown that they can do this by stimulating the rather depressed functioning of the members of the mononuclear phagotic system. The exact mechanism of action of these drugs is discussed with particular emphasis on coumarin which is one of the components of Venalot. PMID- 6255263 TI - The Na-K-ATPase in relation to the Na, K and taurine levels in the senile cataract. PMID- 6255264 TI - Hormonal interaction and ocular pressure in bilateral cervical sympathetic ganglionectomized rabbits. PMID- 6255265 TI - The effect of some antiviral drugs on the cell metabolism in the eye. PMID- 6255266 TI - [Results of surgical treatment of bronchiogenic carcinoma and nonsurgical treatment of oat cell carcinoma (author's transl)]. AB - Of 1732 patients, 95% were followed up. The proportion of men to women was 7:1, most patients being about 70 years old. Eighty percent of the patients smoked, 64% were considered inoperable when first seen, and 4% were found to be incurable at the time of surgery. Postoperative deaths were 8.2%; 3 bronchopleural fistulas and 17 pleural empyemas complicated recovery. Of those patients operated on without lymph node involvement, the 5-year survival rate was 45.4%, with lymph node metastasis 14.7%. Of 242 patients with oat cell carcinoma who were not operated on, 85% died within the first year after hospital discharge. Only 1.2% survived 5 years. PMID- 6255267 TI - [Diagnosis and treatment of rare tumors in the laryngeal-pharyngeal area (author's transl)]. AB - From 1968 to 1979, 11 patients with rare tumors in the laryngeal-pharyngeal area have been treated by the Department of otolaryngology at the University hospital Homburg-Saar. These 11 cases consist of 6 benign and 5 malignant tumors. The malignant tumors were irradiated postoperatively by the Department of Radiology. There was found in the pharyngeal area 1 malignant despeciated leiomyoma, 2 malignant synovialomas and in the laryngeal area 4 local nongeneralised amyloidosis, 1 hamartoma, 1 chemodectoma, 1 pleomorphic rhabdomyosarcoma of the larynx and 1 primary "oat-cell" carcinoma. The initial exploratory excisions often led to an incorrect diagnosis: The final one was made postopertively. The large number of preoperative wrong diagnoses leads to the demand to only operate after extensive exploratory excisions. PMID- 6255268 TI - [Primary malignant mesenchymal tumors in the head and neck area--the problems in diagnosis and therapy (author's transl)]. AB - The problems in diagnosis and therapy of malignant mesenchymal tumors in the head and neck area are reported on. The clinical course and the pathology of these rare tumors are described. First hand experiences with certain cases--one malignant leiomyoma, two rhabdomyosarcomas (one of embryonal and one of pleomorphic type), a haemangiopericytoma, a haemangioendothelioma, a chondrosarcoma and two malignant synovialomas are detailed and compared with similar case-studies in the literature. PMID- 6255269 TI - [Malignant medio-facial granuloma with hepatic and renal metastases]. PMID- 6255270 TI - [Bronchial tumors with granulated cells (Abrikossof's tumor). Apropos of 2 case]. PMID- 6255271 TI - Multiple receptors for brain dopamine in behavior regulation: concept of dopamine E and dopamine-I receptors. PMID- 6255272 TI - Vitamin D in lactation. I. The localization, specific binding and biological effect of 1,25-dihydroxyvitamin D3 in mammary tissue of lactating rats. PMID- 6255274 TI - Changes in mouse brain diazepam receptor binding after phenobarbital administration. PMID- 6255273 TI - Role of extrarenal and intrarenal converting enzyme inhibition in renal vasodilator response to intravenous captopril. PMID- 6255275 TI - Morphine acts through alpha adrenergic and serotoninergic neurons to stimulate growth hormone secretion in the dog. PMID- 6255276 TI - Reduction by beta-endorphin of efflux of dopamine and DOPAC from superfused medial basal hypothalamus. PMID- 6255277 TI - Demonstration of acute and chronic effects of dietary fibre upon carbohydrate metabolism. PMID- 6255278 TI - The pharmacology of prazosin, a novel antihypertensive agent. PMID- 6255279 TI - The binding of fluorocatecholamines to adrenergic and dopaminergic receptors in rat brain membranes. PMID- 6255280 TI - The effects of nitroglycerin on cyclic nucleotides in the coronary artery in vivo. PMID- 6255281 TI - [Tick-borne encephalitis in Europe (author's transl)]. AB - Tick-borne encephalitis is the major european arbovirosis. It is observed in Soviet Union, Central and Western Europe and Scandinavian countries. In France, natural foci have been detected in Alsace (more specialy in Illkirch forest, near Strasbourg). In the United Kingdom exists a sheep encephalomyelitis (loupingill) caused by an arbovirus not much different from the tick-born encephalitis virus. The tick-born encephalitis virus is a flavivirus transmitted by tick bites. Tick is also a virus reservoir; it remains infected all along its life, through its metamorphosises and transmits the virus to its progeny. Vector-ticks belong to various species of a same genus; Ixodes persulcatus in Far-Eastern Soviet Union, Ixodes ricinus in other european foci. Small rodents (field-mouse, vole) are mainly the prime vertebrate hosts. Man is more often infected by the tick bite, more rarely by ingestion of new milk from infected domestic animals. Prognosis of the disease is under geographical variations: severe in Far-Eastern Russia and much milder in Central Europe. Natural foci are detected by serological surveys in patients recovering from neurologic diseases, human populations and in domestic animals. Natural foci beeing localized, isolation and identification of the virus from ticks and local rodents are tried. Extension and creation of new natural foci are caused by big mammalians and by migratory birds which carry over virus and vector ticks. Prophylaxis for people going to or living in registered natural foci, consists of avoiding ticks bites by wearing tight clothes and using repellents. Immunization by a recent vaccine produced in Austria from cultures on chicken embryo has given promising results. PMID- 6255282 TI - [Control of arboviral encephalitis in China (author's transl)]. AB - Japanese B encephalitis is the most important and widespread arbovirus disease in China. Except Tibet and Sinjiang autonomous regions, it occured in every province. JBE virus were isolated from six species of Culex, three species of Aedes, one species of Anopheles and Lasiohelea. The main vector of JBE virus in China is Culex tritaeniorhynchus. The main spreading reservoir host, no doubt, is the pig, but the persistant reservoir is not clear yet. Vaccination of the children under ten years is an efficient measure to control the epidemics of JBE. However, integrated measures will ensure better results. It includes health educational programmes, vaccination, early applying larvicidal insecticides, residual spraying in livestock pens, biological measures against mosquitoes in rice fields. PMID- 6255283 TI - [Measurement and evaluation of air contamination by dust in the Federal Republic of Germany]. AB - The paper presents hygienic standards, either currently valid in the GFR or planned to be introduced in 1982, for industrial dusts containing free crystalline silica and asbestos. In addition, methods and apparatus for measuring dust respirable fraction concentrations at workplaces are discussed, as well as principles of work conditions evaluation and hygienic interpretation of measurements results. The basis of this interpretation is an assumption that the MAK (Maximale Arbeits-platzkonzentrationen) values for the dusts containing crystalline forms of silica and TRK (technische Richtkonzentrationen) for the dusts containing asbestos are average values for 1 year. Dustiness at workplaces is also evaluated for 1 year. PMID- 6255284 TI - Bacillus subtilis-phage phi 1 overcomes host-controlled restriction by producing BamNx inhibitor protein. AB - Bacillus amyloliquefaciens N produces two restriction enzymes, BamNI and BamNx. Subtilis-phage phi 1 is strongly restricted by BamNx. We isolated phi 1 rH, a mutant of phage phi 1, which overcame the BamNx-restriction by producing inhibitor. This inhibitor inactivated BamNx specifically and reversibly. The inhibitor directly interacted with BamNx and the inactivation might be the result of formation of a binary complex. The inhibitory activity was sensitive to treatment with trypsin. The molecular weight of the inhibitor protein was estimated to be approximately 20,000 daltons by gel filtration. PMID- 6255285 TI - The origin of Q-independent derivatives of phage lambda. AB - lambda qsr' (Q-independent) phages are characterised by the replacement of the region of the lambda genome that contains Q, S, R, and the late gene promoter, P'R, with host-derived DNA that codes for functions analogous to those deleted. Restriction endonuclease analysis and DNA/DNA hybridisation methods have been used to show that lambda p4 and lambda qin A3, two such Q-independent phages, are the product of recombination between lambda and a defective lambdoid prophage (the qsr' prophage) located at an as yet unidentified site in the E. coli K 12 chromosome. The qsr' prophage is distinct from the defective lambdoid prophage Rac (Kaiser and Murray 1979). In the E. coli K12 strain AB1157 from which lambda qsr' phages cannot be generated, the qsr' prophage has suffered an internal deletion. That the qsr' prophage appears not to carry a full complement of essential late genes suggests one explanation for its apparently defective nature. PMID- 6255286 TI - Plasmid cloning vectors that can be nicked at a unique site. AB - We describe ColEl-type plasmids, with relaxed DNA replication, based on pMB9, and carrying the CmR determinant of R1, in addition to the TcR determinant of pMB9. One of the plasmids, pPH207, has unique sites for EcoRI, HindIII, BamI, SalI and HpaI. Insertion of foreign DNA into all but the last of these inactivates either the CmR or the TcR determinant. The original CmR TcR plasmid (pCM2) contains a copy of IS1 which produces deletions to left and to right. Most of these inactivate either the CmR or the TcR determinant. An internal 280 bp deletion of IS1 DNA in pPH207 greatly reduces the frequency at which deletions are observed. The main feature of these plasmids is a site that is cleaved by some preparations of EcoRI in only one strand of the DNA duplex (the EcoRIn site). This site facilitates strand separation of sequences inserted at the HindIII, BamI and SalI sites of the TcR gene, and also of any inserted at the true EcoRI site by a method that destroys that site. Since the orientation of the EcoRIn site is known, the orientation of sequences inserted at the neighbouring sites can be easily determined. Plasmid pPH207 is not mobilised by a Hfr, but its mobilisation is promoted by ColEl. It is therefore Mob- bom+. Experiments with minicells show that it directs the copious synthesis of chloramphenicol transacetylase. PMID- 6255287 TI - Construction of pBR322-ara hybrid plasmids by in vivo recombination. AB - In vivo recombination was used to clone deletions of the araBAD-araC genes of Escherichia coli onto a hybrid pBR322-ara plasmid. Genetic and physical analyses demonstrated that the desired deletions had been recombined onto the plasmid. In addition to permitting a detailed physical analysis of various ara deletions, this procedure has generated a series of plasmid cloning vehicles that can be used to clone, by in vivo recombination, any ara point mutation located within the region covered by the deletions. Hybrid plasmids containing the cloned point mutation can be distinguished from the original cloning vehicle by genetic complementation. The desired recombinant plasmid can be easily obtained because the frequency of recombination between the plasmid ara region and the chromosomal ara region is 0.025%--3%. A plasmid containing a deletion which removes the ara controlling site region and the araC gene was used to clone two types of araBAD promoter mutations and an araC mutation by in vivo recombination. Genetic and physical analysis of these plasmids established that the mutations in question had been recombined on to the ara deletion plasmid. The application of this procedure to the ara genes and to other genetic systems is discussed. PMID- 6255288 TI - Involvement of DNA gyrase in rRNA synthesis in vivo. AB - The effects of oxolinic acid and novobiocin, two known inhibitors of DNA gyrase, on in vivo transcription in E. coli were investigated. The drugs inhibit the incorporation of 3H-uridine into RNA. It is shown that the effect is due to a direct influence of DNA gyrase on transcription, independent of interference with replication. By the use of rifampicin and hybridization experiments it was found that treatment with intermediate concentrations of DNA gyrase inhibitors reduces the rate of rRNA synthesis to a smaller extent than the rate of total RNA synthesis. By following the completion of growing rRNA chains we have also obtained evidence indicating that the average rate of rRNA chain growth is decreased in cells treated with inhibitors of DNA gyrase. PMID- 6255289 TI - A physical map of the permuted genome of bacteriophage T1. AB - A restriction map has been constructed for the DNA of coliphage T1 which locates the cleavage sites of the restriction endonucleases, BglI (6 cuts), BglII (16 cuts), EcoRI (2 cuts), HindIII (2 cuts) and PstI (2 cuts). Digestions with BglI and BglII reveal fragments which are present in sub-molar quantities. Two methods, one using the selective removal of molecular ends with exonuclease III and the other involving the comparison of digestion patterns of concatemeric and virion DNA, have shown that the submolar fragments are at or close to the ends of the molecules. Digestions with BglI show that one terminal fragment has a very precise molecular weight whereas all the others are of heterogenous molecular weight. These results are consistent with the model for DNA packaging in which maturation is initiated at a precise site on a concatemeric precursor and proceeds by the encapsidation of up to four successive 'headfuls' of 1.065 genome equivalents (MacHattie and Gill 1977). PMID- 6255291 TI - Isolation of an IS1 flanked kanamycin resistance transposon from R1drd19. AB - We have isolated and identified an IS1-flanked transposon from the plasmid R1drd19. This transposon specifies resistance to kanamycin and is 10.4 kg long. It exhibits a frequency of transposition two orders of magnitude lower than that of the smaller, IS1-flanked transposon Tn9. We have named it Tn2350. PMID- 6255290 TI - Genetic and physical mapping of recF in Escherichia coli K-12. AB - Two factor transductional crosses place recF at approximately 82 min on the E. coli chromosome; recF is highly cotransducible with dnaA and gyrB (cou). Transductional analysis with a series of lambda tna specialized transducing phages carrying chromosomal DNA from the tnaA region place recF between dnaA and gyrB. This analysis also indicates that a gene lying in the same region and producing an easily detectable protein (estimated MW of 45 kD) is dnaN and not recF. PMID- 6255292 TI - Isolation of E. coli mutants containing multiple transpositions of IS sequences. AB - The characterization of three E. coli mutants that appeared to have unselected IS1 insertions on the chromosome are described. One had a single new IS1 sequence. The second had three new IS1 sequences. The third had two new IS1 sequences and one of the IS1 sequences in the parent was missing. These mutants were found in a collection on strains that contained IS insertions in the spc operon. The frequency of finding mutants with unselected IS1 transpositions was at least 100 times greater than expected. The results suggest several transposition events may frequently occur in the same cell. PMID- 6255294 TI - Interactions between the F conjugal transfer system and CloDF13::Tna plasmids. AB - It was confirmed that all the F transfer genes required for the formation of stable mating pairs, including traN and traG, are essential for transfer of the two small multicopy plasmids ColE1 and cloDF13, whereas the traM, traI and traZ genes that are required for F conjugal DNA metabolism, are not. Differences between ColE1 and CloDF13 were that the F traD gene was needed for transfer of ColE1 but not of CloDF13, and that R100-1 efficiently transferred CloDF13 but not ColE1. A copy number mutant of CloDF13 inhibited F transfer and reduced plaque formation by the F-specific RNA phage f2, but not by Q beta or by the single strand DNA phage f1. This phenotype suggests that the inhibition system (FinC) acts on traD, mutations in which give a similar phenotype. Hybridisation experiments with lambda tra phage DNA showed that transcription of traD was not reduced, and FinC probably inhibits function of the traD product rather than its synthesis. FinC-insensitive Flac mutants were isolated and characterised. One was shown to have an uppromoter mutation resulting in increased transcription of traJ and hence of the traY leads to Z operon including traD: the raised level of the traD product presumably then counteracted FinC inhibition. PMID- 6255293 TI - Recombinant P4 bacteriophages propagate as viable lytic phages or as autonomous plasmids in Klebsiella pneumoniae. AB - We demonstrate the use of bacteriophage P4 as a molecular cloning vector in Klebsiella pneumoniae. A hybrid P4 phage, constructed in vitro, that contains a K. pneumoniae hisDG DNA fragment can be propagated either as a lytic viable specialized transducing phage or as an autonomous, self-replicating plasmid. Hybrid P4 genomes existing as plasmids can be readily converted into non defective P4-hybrid phage particles by superinfection with helper phage P2. Infection of a K. pneumoniae hisD non-P2 lysogen with P4-hisD hybrid phage results in approximately 90% of the infected cells becoming stably transduced to HisD+. Because P4 interferes with P2 growth, high titre stocks of P4 hybrid phages are relatively free (less than or equal to 10(-6) of P2 contamination. The hisG gene product was detected in ultraviolet light irradiated host cells infected by the P4-hisDG hybrid phage. A mutant of P4 (P4sid1) that directs the packaging of P4 DNA into P2 sized capsids should permit the construction of hybrid phages carrying 26 kilobase inserts. PMID- 6255295 TI - The hsd (host specificity) genes of E. coli K 12. AB - The hsd genes of E. coli K 12 have been cloned in phage lambda by a combination of in vitro and in vivo techniques. Three genes, whose products are required for K-specific restriction and modification, have been identified by complementation tests as hsdR, M and S. The order of these closely linked genes was established as R, M, S by analysis of the DNA of genetically characterised deletion derivatives of lambda hsd phages. The three genes are transcribed in the same direction but not necessarily as a single operon. Genetic evidence identifies two promoters, one from which transcription of hsdM and S is initiated and a second for the hsdR gene. The hsdR gene codes for a polypeptide of molecular weight approximately 130 000; hsdM for one of 62--65 000 and the hsdS gene was associated with two polypeptides of approximately 50 000. Circumstantial evidence suggest that one of these two polypeptides may be a degradation, or processed, derivative of the other. The hsdS polypeptide of E. coli B has a slightly higher mobility in an SDS-polyacrylamide gel than does that of E. coli K 12. A probe comprising most of the hsdR gene and all of the hsdM and S genes of E. coli K 12 shares extensive homology with the DNA of E. coli B but none with that of E. coli C. PMID- 6255297 TI - Evolutionary divergence of mitochondrial DNA from Paramecium aurelia. AB - Mitochondrial (mt) DNA from four sibling species within the Paramecium aurelia complex, including stocks of different geographic origin and mutants, were analyzed using four 6-bp recognition site and one 4-bp recognition site endonucleases and the sequence divergence was estimated using Upholt's (1977) statistical procedure. All four species were readily distinguishable regardless of the restriction endonuclease employed. With intraspecies comparisons, no differences were observed which could be accounted for on the basis of geographic origin. Except for species 4, each stock (and mutant) gave a species-specific fragment pattern. For species 4, while the patterns were distinct from the other species, two species-specific type of patterns were found, designated A and B. The sequence divergence between these was estimated to be between 1 and 2 percent. With interspecies comparisons, the sequence divergence ranged from 3.9 to 10.3% with the greatest divergence being between species 1 and 4, and the least between species 1 and 5. The similarity between species 1 and 5 is in accord with other criteria for interspecies comparisons. The degree of sequence divergence measured here in Paramecium mt DNA is well within the range reported for rodents and primates. All four species mt DNA were cleaved to many DNA fragments by DPN II, an enzyme which recognizes non-methylated sites, and not by DPNI, the methyl-site specific counterpart of DPN II, suggesting that mt DNA from Paramecium aurelia is not appreciably methylated, if at all. PMID- 6255296 TI - High frequency mobilization of the chromosome of Escherichia coli by a mutant of plasmid RP4 temperature-sensitive for maintenance. AB - Two mutants of plasmid RP4 temperature-sensitive for maintenance were isolated and one of them (pTH 10) was extensively studied. Cells carrying pTH10 showed temperature-sensitive drug resistance from which we isolated a number of temperature-independent derivatives. Almost all of them were Hfrs donating chromosomal genes to recipient bidirectionally from different points of origin. The Hfrs may be formed in two steps: (1) the transposon (Tn 1) carried by pTH 10 translocates into the host chromosome, and (2) pTH 10 is integrated in the host chromosome by reciprocal recombination between the TN 1 s, one situated on pTH 10 and another on the host chromosome. That temperature-independent drug resistance selects for this type of derivative, was supported by the following observations: (1) Hfrs thus obtained were usually unstable and segregated at high frequency 'revertants' showing temperature-sensitive drug resistance when they were cultivated at 30 degrees C. (2) The 'revertants' cured of pTH 10 were still ampicillin resistant, indicating existence of Tn 1 inserted in the host chromosome. (3) Tn 1 insertions found in these derivatives mapped in the vicinity of points of origin of the original Hfrs. (4) When new Hfrs were constructed by: (a) transduction with Plkc on Tn 1 insertions found in derivatives of Hfrs, (b) introduction of pTH 10 into the transductants,and (c) isolation of clones of temperature-independent drug resistance from such pTH 10 carrying stains, they had similar characteristics to the original Hfrs from which Tn 1 insertions were derived. Possibilities for genetic manupulation using pTH 10 in a wide range of Gram-negative bacteria are discussed. PMID- 6255299 TI - Polymorphic trophonosis: the pseudo-omnivorous diet-related disease--a hypothesis. AB - Consideration of a wide range of seemingly disparate, non-infectious diseases reveals that most of them are only the varying forms or symptoms of a single, diet-related disease postulated to be Polymorphic Trophonosis. It is pointed out that they are all associated with pseudo-omnivorous dietary practices--negating the biological limitations of Homo omnivorus. In these practices, neither the out of-all-proportion consumption of certain essential nutrients nor the liberal eating of new types of food seems to be suitable to the structure and mode of functioning of the digestive and/or metabolic systems. PMID- 6255298 TI - Tn1 generated mutants in the mercuric ion reductase of the Inc P plasmid, R702. AB - Physiological, biochemical and genetic aspects of resistance to inorganic mercury compounds were examined in a group of mercury sensitive derivatives generated in the Inc P plasmid, R702, by Tn1 insertion. Strains carrying each of these insertion mutations had no detectable mercuric ion reductase, were more sensitive to mercuric ion than a plasmidless strain, and exhibited inducible uptake of Hg2+. These characteristics indicate that the mutants are altered in the Hg(II) reductase. This hypothesis was supported by complementation and recombination analysis with known point and deletion mutations in the mer operon of the Inc FII plasmid, R100. Such experiments showed that the eight insertions studied had occurred in four distinct regions of the Hg(II) reductase structural gene (merA). Complementation data also demonstrated that the regulatory protein determined by the R702 plasmid has no effect on the expression of the micro-constitutive Hg(II) reductase activity expressed by merR mutants of R100. PMID- 6255300 TI - [Endocrine therapy only in hormone-receptor-positive breast neoplasms]. PMID- 6255301 TI - Hepatitis A-virus in cell culture: I. propagation of different hepatitis A-virus isolates in a fetal rhesus monkey kidney cell line (Frhk-4). AB - A fetal rhesus monkey kidney cell line (Frhk-4) was infected with different hepatitis A-virus (HAV) isolates GBG, GBM, GJA. The time-dependent absorption of the HAV isolates of Fhrk-4 cells was measured. Replication of all three isolates in these cells could be demonstrated intracellularly 8--10 weeks after infection, and release of HAV into the supernatant some 10--15 weeks after infection could be shown. The specificity of the virus determination by RIA from supernatants of HAV-infected cells from passages 1, 2, and 3 in Frhk-4 cells was shown with sera that were collected from a chimpanzee infected with MS-1 both before infection as well as during convalescence. These results were subsequently compared with sera collected from human patients before the onset of hepatitis as well as during convalescence. With immunofluorescence microscopy a cytoplasmic fluorescence could be shown in HAV-infected Frhk-4 cells and finally the release of 27 nm HAV particles into the supernatant of HAV-infected Frhk-4 cells could be demonstrated by immune electron microscopy. PMID- 6255302 TI - Cancer of the extrahepatic bile ducts. AB - Case histories of 47 patients with histologically confirmed carcinoma of extrahepatic bile ducts presenting to M. D. Anderson Hospital and Tumor Institute over a 30-year period were studied. The disease was more common in males during the sixth and seventh decades of life. A third of the patients had history of cholelithiasis. Four patients had prior history of chronic ulcerative colitis and one patient had congenital choledochal cyst prior to development of cancer of the bile duct. Jaundice was the earliest and the most common presenting sign. The tumor was located in the common bile duct more often than in the hepatic ducts. The overall median survival was eight months with two-year and five-year survival rates of 15% and 3%, respectively. The respective values for patients who had resectable tumors were 21.7 months, 57% and 20%. Ascending cholangitis was a frequent complication in patients treated with dilation and intubation and, overall, hepatic failure and systemic infection were more frequent causes of death than distant metastases. PMID- 6255303 TI - [Pancreatic insulinoma]. PMID- 6255304 TI - Three multifunctional protein kinase systems in transmembrane control. PMID- 6255305 TI - Specific interaction of base-specific nucleases with nucleosides and nucleotides. PMID- 6255306 TI - The cytochromes c: paradigms for chemical recognition. AB - The cytochromes c include subgroups which present a variety of redox functions based on well-defined changes in the basic three-dimensional structure exemplified by the mitochondrial and certain bacterial forms, in particular cytochromes c2. These proteins exhibit overlapping functionality and a graded sequence of structures which provide paradigms well suited for clarification of recognition mechanisms. The character and distribution of cytochromes c will be discussed and approaches to relatedness of structure and function will be described, based on kinetic analyses of cross reactivities of cytochromes c2 with mitochondrial cytochrome c oxidase. PMID- 6255307 TI - Site-specific mutagenesis in the analysis of a viral replicon. PMID- 6255308 TI - Recognition of ligands by haem proteins. PMID- 6255311 TI - Protein phosphatase from rat liver nuclei. AB - Protein phosphatase, active on non-histone phosphoprotein substrate, was partially purified from rat liver cell nuclei by means of salt extraction, ammoniumsulfate precipitation, DEAE cellulose chromatography, gel filtration and preparative isoelectrofocusing. Rat liver nuclei contain a heterogenous population of different protein phosphatases. All the enzyme fractions eluted from DEAE cellulose are of low molecular weight between 12,000--31,000. The pH 5.5 peak fraction of preparative isoelectrofocusing was characterized in detail. It has a pH optimum of 6.8 using nuclear phosphoprotein substrate. It is inhibited by Na+ at 80 mM, and to a lesser extent by K+, activated by Mg2+ (5 mM) and Mn2+ (1 mM). However, the latter is inhibitory at 6 mM. The nuclear protein phosphatase is also active on labelled F1 and F2b histones and casein, however, its V is lower on histones and it contains component(s) active specifically on nuclear phosphoprotein substrate but not on casein. PMID- 6255309 TI - The molecular basis of disorders of human hemoglobin synthesis. AB - The structure and organization of the human globin genes at the nucleotide level has been established by restriction endonuclease digestion of cellular DNA, and by the isolation and purification of these genes in phage vectors. With this approach it has been possible to define alterations at the DNA level resulting in a group of inherited diseases of man known as the thalassemia syndromes, and related disorders. Combined with other known genetic and biochemical data, these studies provide a framework for understanding the pathogenesis of these disorders at the molecular level. PMID- 6255312 TI - [Genome instability]. AB - The paper deals with the various manifestations and the role of genome changes, mainly in eukaryotes. I. Hereditary changes: 1) multiplication of genes in animals; 2) multiplication of genes in prokaryotes; 3) microsymbionts, mobile elements and supermutability; 4) extrachromosomal element delta in Drosophila; 5) hybrid dysgenesis in Drosophila; 6) mobile and unstable genes in drosophila; 7) controlling elements in planrs. II. Genome changes as a regulatory factor of genetic activity: 1) immunoglobulin genes; 2) mating types in yeast; 3) the inversion mechanism of switching gene activity in prokaryotes; 4) ribosomal and histone genes; 5) changes of DNA fractions in ontogenesis; 6) regulation of genome changes. PMID- 6255313 TI - [Cloning and restriction analysis of the 3 micron DNA of Saccharomyces cerevisiae]. PMID- 6255314 TI - [Changes in the induction and repair of double-stranded DNA breaks in pro- and eukaryote cells. I. Use of a Zimm elastoviscosimeter to study induction of double stranded DNA breaks in gamma-irradiated Escherichia coli cells]. AB - The technique of elastoviscosimetry allows to study the induction of double strand breaks in DNA of E. coli at low doses (on the order of D37). The dose dependence of retardation time to shows a characteristic maximum. It is shown that the ascending part of the curve is due to the phenomenon of relaxation of supercoiled DNA in the bacterial nucleoid. Relaxation is effected by different gamma-induced damages in DNA which are not double-strand breaks. The position of the maximum yields the average dose for the formation of the first double-strand break, which transforms the circular DNA into a linear chain. The descending part of the dose curve is explained by accumulation of additional double-strand breaks. The gamma-irradiation and lysis of cells was performed in different media. It was found that only in the case when the action of nucleases was substantially (but not completely) inhibited, the position of the maximum of the dose dependent of retardation time coincides satisfactorily with the value of D37 (14.5 +/- 2.3 and 12.5 +/- 3 krad correspondingly). If the medium does not contain inhibitors of nucleases then the position of the maximum corresponds to a 4.2 times lower dose of gamma-rays. This shows that double-strand breaks in gamma irradiated DNA are generated mainly by enzymes participating in repair processes and that the first double-strand breaks seems to be the true reason of lethality because of inability to be repaired. PMID- 6255315 TI - [Physico-chemical principles for discrimination of sodium and potassium ions by membrane Na pumps. I. Effect of organic compounds on the ionic specificity of Na, K-ATPase]. AB - Effects of some organic compounds of different hydrophobicity on the structure and ion specificity of the sodium-potassium adenosine triphosphatase (Na,K ATPase) membrane preparation were studied. Inhibition abilities of these compounds correlate well with their lipophilic properties. High hydrophobic compounds change mainly the enzyme activation by potassium ions and the spin label mobilities in hydrophobic regions of the membrane preparation. Polar species, in contrast, influence the enzyme activation by sodium ions and the surface polar properties of the membrane preparation. It is supposed, that the Na,K-ATPase activations by potassium and sodium ions are correspondingly related to hydrophobic regions of the lipoprotein enzyme complex and to the polar regions stabilized by hydrogen bonds. PMID- 6255316 TI - [Study of binding of spin probes of the carboline and benzocarboline series to bovine serum albumin]. AB - The dependence of the external and internal wide hyperfine extreme shifts of the ESR spectra on temperature and viscosity for spin-probes in solution of BSA was studied. Seven homologous spin-probes of carboline and benzocarboline derivatives were used. The obtained dependences are a consequence of the involvement of the spin-probe in two types of rotation: an anisotropic fast reorientation with tau > 10(-9) s with respect to a macromolecule and the isotropic one with tau > 10(-8) s due to rotation of the macromolecule itself. It was shown, that extrapolation values of a separation between hyperfine extreme do not reflect the degree of the immediate spin-probe environment polarity, but are determined by the hyperfine tenzor partial averaging as a result of the rapid anisotropic reorientation of the spin-probe. All spin-probes used were shown to be bound by the BSA molecule in the near vicinity of the tryptophan residue. The rotation correlation time of the BSA molecule was determined to be equal to 40 ns. PMID- 6255317 TI - [Study of the conformational situation in an aqueous solution of dinucleoside phosphates using proton spin lattice relaxation]. AB - With the use of experimentally measured spin-lattice relaxation rates of H(5), H(6), H(2), H(8) and H(1') the analysis of the conformational situation in aqueous solution of CpC, CpA, ApC and ApA has been carried out. In all cases, the close state is shown to be described by the equilibrium of right- and left-handed forms. The right-handed forms are favourable for all DNP studied and are related to the "canonical" Pba type. On the contrary, the possibility of realization of one or the other noncanonical forms (these are mainly left-handed conformers) is determined strictly by nucleotide sequences. The noncanonical conformers for CpC and CpA are Mbb forms, in which both monomeric units are characterized by anti conformation, and the base of the 3'-end is turned 180 degrees around the glycosidic bond as compared to the canonical form. The forms of Mab type are possible for ApC. In this case, the purine monomer exists in syn-, but the pyrimidine monomer--in anti-conformation. Both bases are turned to 180 degrees. Finally, in the case of ApA, the forms of Mba type with high-anti-conformation of both monomers are realized. The conformational behaviour of oligonucleotides and the possible biological role of noncanonical conformations are discussed taking into consideration the results obtained. PMID- 6255310 TI - Double-stranded RNA. AB - High molecular weight, fully double-stranded RNA (dsRNA) has been recognized as the genetic material of many plant, animal, fungal, and bacterial viruses (Diplornaviruses): virusspecific dsRNA is also found in cells infected with single-stranded RNA viruses. DsRNA has identified in a variety of apparently normal eucaryotic cells and is associated with the "killer" character of certain strains of Saccaromyces cerevisiae. PMID- 6255318 TI - The terminal stages of immune hemolysis--a brief review. PMID- 6255319 TI - Trophoblastic disease, a bridge between pregnancy and malignancy. PMID- 6255320 TI - [Functional anatomy of shoulder-arm pain (author's transl)]. AB - The treatment of pains felt in the shoulder-arm region depends on the pathogenesis of the individual case. For this reason the functional anatomical conditions which can cause pain in various diseases are first described. This is followed by a presentation of the pathophysiological mechanisms of the causation of pain. The shoulder girdle is a functional skeletal motor unit which includes joints and muscles of the arm, neck and trunk. Disturbances of one structural element of the shoulder girdle are reflected as muscular distortion of the entire shoulder girdle and possibly also of the neighboring parts of the body communicating with the shoulder girdle. Shoulder-arm pain can arise in principle from two different sources: stimulation of pain receptors (receptor pain, physiological excitation of pain) and by functional disturbance of pain conducting and pain producing neuronal structures. PMID- 6255321 TI - [Business with "God's Pharmacy"]. PMID- 6255322 TI - Untransformed xeroderma pigmentosum cells are not hypersensitive to sister chromatid exchange production by ethyl methanesulphonate--implications for the use of transformed cell lines and for the mechanism by which SCE arise. AB - A transformed cell line, XP12RO(SV40) has previously been found to be hypersensitive to several chemical mutagens including ethyl methanesulphonate, as judged by sister-chromatid exchange (SCE) formation. The hypersensitivity of this line has been confirmed for SCE formation and extended to cell survival. Measurements of SCE formation and survival show, however, that the hypersensitivity of the XP12RO(SV40) cell line is not typical of the primary strain (XP12RO) from which the transformed line was derived, nor it is typical of other primary strains also belonging to complementation group A (XP4LO, XP25RO). These results suggest that reports based on single cell lines must be viewed with caution and that the relationship between unexcised damage in DNA and SCE production is uncertain. PMID- 6255323 TI - High sensitivity but normal DNA-repair activity after UV irradiation in Epstein- Barr virus-transformed lymphoblastoid cell lines from Chediak--Higashi syndrome. AB - We established lymphoblastoid cell lines from 2 children with Chediak--Higashi syndrome (CHS), 2 xeroderma pigmentosum (XP) patients and control donors after transformation of peripheral lymphocytes by Epstein--Barr virus (EBV). We used these lymphoblastoid cell lines to investigate repair activity after ultraviolet irradiation. Cell survival of both CHS lymphoblastoid cell lines after irradiation by UV and treatment by 4-nitroquinoline 1-oxide (4NQO) fell between those of the XP and control cell lines. Unscheduled DNA synthesis of CHS cells after UV irradiation occurred at rates similar to those of control cells. PMID- 6255324 TI - Altered control of gene activity in the soma by carcinogens. PMID- 6255325 TI - Induction of prophage and mutagenic effects by alkyl alkylaminosulfonates, ethyl aminosulfonate and alkyl methanesulfonates. AB - Prophage induction and mutation by alkylaminosulfonates, ethyl aminosulfonate and alkyl methanesulfonates were examined comparatively. Prophage induction was carried out with a lysozyme lysis technique on the lysogenic strain Micrococcus lysodeikticus 53-40 (N5). The sulfonic ester derivatives show a slight lysogenic induction. At higher concentrations their toxicity seems to mask phage detection. Only methyl isopropylaminosulfonate and ethyl aminosulfonate exhibit no or negligible toxic effects, and with these compounds at higher concentrations a strong prophage induction is found. Alkyl sulfonate derivatives induce mutations in the tester strain of Salmonella typhimurium TA1535. Methyl methylaminosulfonate and ethyl N-methyl-N-2-chloroethyl aminosulfonate show a mutagenicity comparable to that of the well-known methyl methanesulfonate or ethyl methanesulfonate. With ethyl aminosulfonate, however, which does not show inactivation, no significant mutagenic effect was observed. DNA alterations were found in the polymerase-deficient strain E. coli P3478. The results of prophage induction and mutagenicity are compared and discussed. PMID- 6255326 TI - Evidence for a branched electron transport chain in Trypanosoma brucei. AB - The flow of electrons the terminal oxidases present in the bloodstream and procyclic trypomastigotes of Trypanosoma brucei LUMP 1026 has been investigated by the use of salicylhydroxamic acid (SHAM) and cyanide. Respiration in bloodstream trypomastigotes was completely inhibited by 0.5 mM SHAM with a Ki below 10 microM. The Ki for SHAM in procyclic trypomastigotes was 70 microM. In procyclic trypomastigotes there are at least three terminal oxidases of which the two major ones are cytochrome aa3 oxidase, sensitive to cyanide inhibition, and alpha-glycerophosphate oxidase (GPO), sensitive to SHAM inhibition. These two oxidases contribute 60 and 30%, respectively, to total cell respiration. Inhibition of the cytochrome system with cyanide causes an increase in the flow of electrons through the GPO system, and inhibition of the GPO system with SHAM stimulates electron flow in the cytochrome system. Succinate oxidation in the mitochondrial fraction is partially inhibited by SHAM and this SHAM-sensitive respiration is not inhibited by antimycin A. The kinetic data of respiration by procyclic trypomastigotes fit a model proposed by Bahr and Bonner to determine the maximum rates of two competing electron transport pathways. It is concluded that the electron transport chain in T. brucei is branched. PMID- 6255327 TI - cAMP phosphodiesterase and activator protein of mammalian cAMP phosphodiesterase from Trypanosoma cruzi. AB - Epimastigote forms of Trypanosoma cruzi contain a soluble cAMP phosphodiesterase. Optimal activity was found at pH 8.0 and in the presence of 5 mM Mn2+. Other cations were less efficient and did not give rise to an additional stimulation when added in the presence of optimal concentrations of Mn2+. The enzyme is not Ca2+ dependent. The apparent Km of the enzyme for the substrate is 40 microM and no kinetic evidence for the existence of two enzymes has been found. Theophylline and caffein did not inhibit the T. cruzi cAMP phosphodiesterase. The enzyme activity does not change during cell growth suggesting that the fluctuation observed in the levels of cAMP are largely a response to variations in adenylyl cyclase activity. The intracellular concentrations of cAMP ranged between 0.04- 0.15 microM. No evidence that the T. cruzi cAMP phosphodiesterase is regulated by an endogenous activator could be found. However, T. cruzi contains a heat-stable, low molecular weight, non-dialysable protein that activates mammalian cAMP phosphodiesterase in the presence of Ca2+. The properties so far studied of such an activator suggest that it might be equivalent to other Ca2+-dependent regulators described in vertebrate and invertebrate species. PMID- 6255328 TI - Inhibition of malaria parasite invasion into erythrocytes pretreated with membrane-active drugs. AB - Normal rhesus monkey erythrocytes were incubated with various membrane-active drugs (for 1 h at 37 degrees C) and after thorough washing, were exposed to infection with Plasmodium knowlesi in an invitro cultivation system. The ability of merozoites to infect with drug-pretreated erythrocytes was assessed both by counting the number of infected cells and by measuring the incorporation of [3H]isoleucine into parasite protein. Marked inhibition of invasion was observed with vinblastine and colchicine, at concentrations greater than 5 x 10(-4) M, respectively. At similar concentrations, cytochalasin B or amantadine had no apparent effect. The addition of 10(-3) M 3',5'-cAMP to the medium during the incubation in the presence of colchicine or vinblastine partially decreased the inhibitory effects. The effects of colchicine and vinblastine on parasite invasion may be correlated with a reversible alteration in erythrocyte conformation (spherocytosis) which occurs at similar drug concentrations to those above and which can be relieved by simultaneous incubation with cAMP. A possible mechanism of action is proposed. PMID- 6255330 TI - In search of Hodgkin's disease virus. PMID- 6255329 TI - Childhood social environment and Hodgkin's disease. AB - The epidemiologic similarities between Hodgkin's disease in the young and paralytic poliomyelitis suggest that Hodgkin's disease may be a rare consequence of a common infection, with the probability of oncogenesis increasing with age at the time of infection. In a study of 225 cases and 447 controls 15 to 39 years of age, we investigated the association of Hodgkin's disease with factors in childhood that influence age of exposure to infectious agents. Risk among persons with five or more siblings was nearly half that among those with one or none; risk was also reduced among persons of late birth order. Subjects who had lived in multiple-family homes had half the risk of those in single-family housing. Cases had fewer playmates and better-educated mothers than did controls, and cases had twice the rate of infectious mononucleosis. Risk is therefore associated with a set of factors that tend to decrease or delay early exposure to infections, and this association might be explained by a viral origin of the disease, with age at infection as a major modifier of risk. PMID- 6255331 TI - Increased high-molecular-weight thyrotropin with impaired biologic activity in a euthyroid man. PMID- 6255332 TI - Herpes simplex encephalitis: vidarabine therapy and diagnostic problems. AB - To learn more about the treatment of herpes simplex encephalitis with vidarabine, we conducted an uncontrolled study of 132 patients referred to 22 hospitals because of suspected disease. All had a brain biopsy and were started on vidarabine, but only 75 were diagnosed by isolation of virus from a brain-biopsy specimen. Cumulative mortality in the latter group was 39 per cent at one year. Other than therapy, levels of consciousness and age were the major variables that influenced outcome. Of 23 patients under 30 years of age who were lethargic at the initiation of therapy, two died and 16 returned to normal. Of 26 patients over 30 years of age who were lethargic at the outset, nine died and 10 returned to normal. Semicoma and coma were associated with worse outcomes, especially in older patients. Our data suggest that outcome is improved with treatment; they provide more support for the use of brain biopsy to diagnose the infection and indicate a need for better therapy. PMID- 6255333 TI - Hypertension, obesity, and sodium-potassium transport. PMID- 6255334 TI - Hepatitis B vaccine. PMID- 6255335 TI - Surface phenotypes in T-cell leukaemia are determined by oncogenic retroviruses. AB - Spontaneous thymic leukaemia in experimental mice is the result of a complex series of genetically controlled events. An important step in this process involves the production by thymocytes of recombinant polytropic retroviruses (MCF viruses). These leukaemogenic agents arise by recombination of genes from the env regions of endogenous precursor viruses. Sequences in these regions encode the envelope glycoprotein gp70 (ref. 6). Thus far, each cloned isolate of recombinant virus from AKR and HRS/J mice has been found to possess unique oligonucleotide sequences in its env region, as well as clone-specific peptides in its gp70 (refs 7,8). Therefore, the polytropic viruses of these leukaemia-susceptible mice are extremely diverse. These findings suggest that random recombination of env genes gives rise to leukaemogenic polytropic viruses. McGrath and Weissman have proposed that thymocytes with cell surface receptors for the gp70 of a particular leukaemogenic virus are the target cells for malignant transformation by that specific virus. In view of the diversity of polytropic viral gp70, their hypothesis would predict extensive phenotypic diversity among spontaneous thymic leukaemias. In contrast, leukaemias induced by a particular leukaemogenic recombinant virus would always have the same phenotype. Here we verify these predictions experimentally. PMID- 6255337 TI - Freezing induced change in ligand orientation in oxycobalt-myoglobin. AB - Single crystals of oxycobalt-myoglobin were examined by electron paramagnetic resonance (EPR) spectroscopy at ambient and cryogenic temperatures. The principal values and eigenvectors of the g-tensor and the hyperfine coupling tensor were determined. The Co--O--O bond angle was estimated to be 125 degrees at ambient temperature. The single crystal EPR dats of oxycobalt myoglobin at 77K showed two sets of the principal values for g and hyperfine coupling tensors and eigenvectors, indication that the bound oxygen molecule takes two distinct orientations. The result has demonstrated for the first time that the well defined change in the molecular orientation is induced upon freezing the biological macromolecule. PMID- 6255336 TI - Decamethonium and hexamethonium block K+ channels of sarcoplasmic reticulum. AB - The sarcoplasmic reticulum membrane (SR) of skeletal muscle contains cation selective channels which have been detected by isotope fluxes in fragmented SR vesicles, fluorimetric dyes and direct incorporation of SR vesicles to planar phospholipid bilayers. SR channels incorporated in bilayers have a single open state conductance of 140 pS in 0.1 MK+ (refs 4,5). We have previously reported blockade of the SR channel by Cs+, a low-affinity blocker with a zero-voltage dissociation constant of 40 mM (ref. 6). We showed that increasing Cs+ concentrations reduced the open-channel conductance, increased the mean open time and conferred voltage dependence on the open-state conductance. Here we report on the blockade induced by the cholinergic drugs decamethonium and hexamethonium on the SR channel. Although blockade by hexamethonium is similar to that of Cs+, decamethonium blocks with a much higher affinity and induces flickering events which are probably due to the interaction of single drug molecules with the open state. PMID- 6255338 TI - Recognition sequence of bacteriophage phi X174 gene A protein--an initiator of DNA replication. AB - Gene A protein, the initiator protein of bacteriophage phi X174 DNA replication, cleaves synthetic single-stranded oligodeoxyribonucleotides at the same site as the corresponding sequence at the phi X origin. The results identify the recognition sequence within the decamer CAACTTGATA which is cleaved next to the G residue. Further requirements for cleavage of double-stranded DNA by the gene A protein are supercoiling and an A + T-rich domain adjacent to the recognition sequence. PMID- 6255340 TI - beta-Carboline-3-carboxylic acid ethyl ester antagonizes diazepam activity. AB - Analogous to the progression of events in the opiate receptor-enkaphalin area, the first reports that benzodiazepines have selective and specific high-affinity binding sites in brain have stimulated a search for the endogenous 'ligand' or substance that might normally act at these sites. Braestrup and co-workers have extracted from human urine a gamma-fraction (ref. 10) which they have recently identified as beta-carboline-3-carboxylic acid ethyl ester (beta CEE). They reported that this substance is extremely potent in displacing 3H-diazepam from brain binding sites and proposed that a beta-carboline-3-carboxylic acid derivative might, in part, be the endogenous ligand for the brain benzodiazepine receptor. We have examined several synthetically derived beta-carboline-3 carboxylic acid analogues and now present data obtained from testing only the beta CEE described by Braestrup et al. In addition to confirming these workers' observation that this compound is a potent displacer of 3H-diazepam from brain tissue, our pharmacological data indicate that beta CEE has activity that is opposite to, rather than similar to, that of diazepam. PMID- 6255341 TI - Most of the coding region of rat ACTH beta--LPH precursor gene lacks intervening sequences. AB - The peptide hormones ACTH, beta-endorphin, alpha- and beta-melanotropin(MSH) and possibly gamma-MSH are synthesized in the pituitary gland by the processing of a 32,000-molecular weight (MW) polypeptide called proopiomelanocortin (POMC). The existence of a further precursor (pre form) to POMC containing an additional N terminal 'leader' peptide has been suggested by analysis of the in vitro translation products of poly(A)-containing RNA from AtT-20 cells, a mouse ACTH producing cell line of pituitary origin. Nakanishi et al. cloned and sequenced a cDNA copy of the bovine prePOMC mRNA. This sequence confirmed the known structure of the carboxyl half of POMC and revealed the presence of a new MSH-like moiety, gamma-MSH, within the 16,000-MW amino half of the precursor (16K fragment). Recent experiments have suggested that this peptide may act in synergy with ACTH to increase corticosterone and aldosterone production in vivo and in vitro. We have now isolated from a rat genomic DNA library a segment of a DNA encoding most of POMC, using as probe a mouse 144-base pair cloned cDNA fragment encoding beta MSH and beta-endorphin. The cloned rat gene is one of two (or more) closely related POMC genes. The DNA sequence obtained shows that the cloned POMC gene is not interrupted by any intervening sequence (IVS) between the codon for amino acid 19 and the presumptive poly(A) addition site. This region of POMC encodes all the biologically active peptides mentioned above. The DNA sequence encoding the putative gamma-MSH and the coding sequence that precedes it are highly conserved between rat and cow. This may indicate an as yet unrecognized biological function(s) for the NH2-terminal portion of the 16K fragment. PMID- 6255339 TI - External Na dependence of ouabain-sensitive ATP:ADP exchange initiated by photolysis of intracellular caged-ATP in human red cell ghosts. AB - Coupled active transport of Na+ and K+ across cellular plasma membranes is mediated by (Na+ + K+)-stimulated Mg2+-dependent ATPase. Active cation transport by this Na pump involves a cyclic Na-dependent phosphorylation of the enzyme by intracellular ATP and hydrolytic dephosphorylation of the phosphoenzyme, stimulated by K+ (ref. 1). In human red blood cells, skeletal muscle and squid axons, replacement of extracellular K by Na results in a ouabain-sensitive efflux of Na coupled to an influx of extracellular Na. There is apparently no net Na movement nor net hydrolysis of ATP. The rate of Na:Na exchange is stimulated by increased levels of ADP and exchange transport is not observed in cells totally depleted of intracellular ATP. These characteristics suggest that the biochemical mechanism underlying the Na exchange mode of the Na pump involves phosphorylation of the enzyme by ATP (which requires intracellular Na) followed by its dephosphorylation by ADP. Such a reaction has been observed in partially purified (Na+ + K+) ATPase from a variety of sources and its dependence on Na concentration has been described (although not previously for the red cell enzyme). In the present work, intracellular ATP:ADP exchange reaction was initiated by photoreleased ATP following brief irradiation at 350 nm of ghosts containing caged-ATP. The ouabain-sensitive component of the ensuing ATP:ADP exchange reaction shows a biphasic response to extracellular Na. External Na in the range 0--10 mM has an inhibitory effect whilst increasing concentrations beyond this range stimulate the rate of exchange in a roughly linear fashion up to 100 mM Na. These results represent the first direct demonstration of the sidedness of the effects of Na on this partial sequence in the overall enzyme cycle and bear a qualitative resemblance to the Na effects on the Na-ATPase which occur in the absence of intracellular ADP in human red blood cells. PMID- 6255342 TI - Expression of H-2, laminin and SV40 T and TASA on differentiation of transformed murine teratocarcinoma cells. AB - Murine embryonal carcinoma cells (ECCs) do not express antigens of the major histocompatibility complex (H-2), but do express cell-surface molecules shared with early embryos. ECCs are also characterized by their insusceptibility to infection by various oncogenic viruses, and their ability to differentiate into a variety of adult cell types. Differentiation of ECCs in vitro can occur spontaneously or can be induced. On exposure to retinoic acid the ECC line F9 (ref. 13) differentiates into cells which have the characteristics of parietal endoderm. When ECCs are exposed to simian virus 40 (SV40), the SV40 tumour (T) antigen is not expressed, although the virus genome reaches the nucleus, and a primary transcript of the SV40 A gene is made. However, following exposure to retinoic acid, the differentiated cells, like most mouse somatic cells, are susceptible to SV40 abortive infection and synthesize large T and small t antigens. To monitor the molecular events associated with the expression of the SV40 A gene on differentiation, we have constructed an ECC line (F9 12-1) containing a single integrated copy of the SV40 genome. This was accomplished by introducing a recombinant plasmid consisting of pBR322 linked to the herpes simplex type 1 thymidine kinase gene and SV40 genome into a thymidine kinase deficient F9 cell line. We report here that in F9 12-1 cells exposed to retinoic acid, synthesis of the SV40 A gene product(s), T and tumour-associated specific antigens (TASA), parallels the appearance of the normal hallmarks of differentiation in this cell line, H-2 antigens and the basement membrane protein laminin. PMID- 6255343 TI - Myocardial uptake of thallous ion by facilitated diffusion. PMID- 6255345 TI - Survey on antibody to Getah virus in horses in Japan. AB - A seroepidemiological survey was performed on antibody against Getah virus in horses in Japan by the complement fixation test. The positive rate was 35 and 53% in two areas where an outbreak of the infectious disease was reported, whereas it was in a range of 3.3 to 24.2% in other areas, except in certain prefectures of the Kyushu district where a high positive rate was observed. In the Hokkaido district, the northernmost part of Japan, no reactors were found in horses under 6 years old, unlike in any other district. It was also suggested that Getah virus infection might have already been prevalent among horses in Japan before the outbreak of the disease in 1978. It remained to be elucidated, however, that the antibody detected might have been produced by some virus which was antigenically related to Getah virus. PMID- 6255344 TI - [Powdered quartz as an adjuvant in cell-mediated immunity]. PMID- 6255346 TI - Computer simulation of Gumboro disease outbreak. III. Construction model G-4. AB - Following the simulation mode., G-3, of Gumboro disease outbreak, Model G-4 was constructed. The algorithm for computer simulation is shown in a flow chart. The postulates added to those for Models G-1 and G-2 are as follows: (1) The source of contamination is the virus remaining in the house and declining gradually in value with the lapse of time. (2) Any diseased bird excretes the virus during a certain period, so that the virus may be added to the source of contamination. (3) The morbid status of the diseased bird becomes worse in process of time, but the infection remains subclinical until a threshold value is reached. Beyond this value the bird becomes clinically diseased. In this model, more than 20 parameters are involved, and random numbers used for expressing the individual differences in the four variables, viz., the level of innate resistance, parentally conferred immunity, virus-intake, and threshold of clinical manifestation. PMID- 6255347 TI - Computer simulation of Gumboro disease outbreak. IV. Epizootics obtained by mode G-4 with flock size, age and immunity changed. AB - For the computer simulation of Gumboro disease outbreak by Model G-4 a program was written in FORTRAN. Of over twenty parameters involved in the model, the following three were used as input variables: (1) age of chickens at housing a1 (= 1 and 21); (2) size of flock at housing, N(a1) (= 100 and 1,000); and (3) geometric mean of the level of parentally conferred immunity at hatching, G(1) (= 0, 2, 8, and 32). The outputs were the graphic images demonstrating the chronological changes in a flock of innate resistance, parentally conferred immunity, and their sum, and the epizootic patterns composed of numbers of chickens at subclinical stage, clinically diseased, recovered, condemned, etc. at each age. As a result, stronger epizootics were produced at a lower level of parentally conferred immunity, and a higher age and a larger size of flocks. It was suggested that the subclinical stage might not be understood as an inapparent infection, and that a further postulate on the infection might be necessary to be introduced into this model to increase the practical utility, as well as the theoretical soundness, of this series of studies. PMID- 6255349 TI - [A young woman with an enlarged liver]. PMID- 6255348 TI - 1-Methyl-beta-carboline (harmane), a potent endogenous inhibitor of benzodiazepine receptor binding. AB - The interaction of several beta-carbolines with specific [3H]-flunitrazepam binding to benzodiazepine receptors in rat brain membranes was investigated. Out of the investigated compounds, harmane and norharmane were the most potent inhibitors of specific [3H]-flunitrazepam binding, with IC50-values in the micromolar range. All other derivatives, including harmine, harmaline, and several tetrahydroderivatives were at least ten times less potent. Harmane has been previously found in rat brain and human urine, so it is the most potent endogenous inhibitor of specific [3H]-flunitrazepam binding known so far, with a several fold higher affinity for the benzodiazepine receptor than inosine and hypoxanthine. Thus, we suggest that harmane or other related beta-carbolines could be potential candidates as endogenous ligands of the benzodiazepine receptor. PMID- 6255350 TI - [A new point of attack for the treatment of hypertension; captopril, an orally active inhibitor of the enzymatic conversion of angiotensin I into angiotensin II]. PMID- 6255351 TI - [The team work of pathologist-anatomist and pulmonologist; the benefit of doubt]. PMID- 6255352 TI - [Interaction of excitatory and inhibitory processes in the proposed inhibitory interneurons of the hippocampus]. AB - The electrical responses of 25 cells suggested to be hippocampal inhibitory interneurons to stimulation of two afferent fibre systems originated in contralateral hippocampus were investigated in nonanesthetized curarized rabbits. It is stated that the neurons under study have not only high-effective excitatory input but also a weak inhibitory one. The background and evoked activities of the neurons were under predominating influence of the excitatory input which plays a determining role in their behaviour. PMID- 6255353 TI - [Role of different types of infraorbital nerve fibers in synaptic activation of masticatory muscle motoneurons]. AB - The PSPs of the masseter and digastric motoneurons evoked by stimulation of the infraorbital nerve by stimuli from 1 to 10 thresholds were studied in cats anesthetized with chloraloze and nembutal. Masseter motoneurons were divided into two groups. The first group masseter motoneurons responded to 1-2.5 threshold infraorbital nerve stimulation by short latent EPSPs. An increase in the impulse strength to 3-9 thresholds led to appearance of IPSPs with 2.8-3.5 ms latency in these motoneurons. The second group masseter motoneurons responded to 3.9 threshold stimulation of the infraorbital nerve by IPSPs with 6.8 ms latency. The strength of stimuli below 3 thresholds evoked no PSPs in these neurons. Stimuli of 1.1-2.0 thresholds evoked EPSPs in digastric motoneurons but an increased stimulation led to generation of action potentials. It is supposed that existence of different inputs is a basis for functional diversity of jaw-closing and jaw opening reflexes. PMID- 6255354 TI - [Features of the kinetic and stationary characteristics of aconitine-modified sodium channels]. AB - Kinetic and steady-state characteristics of aconitine-modified sodium channels were studied in the Ranvier node membrane. Aconitine-modified sodium channels are shown to be inactivated only partially. The voltage dependence of the fraction of noninactivated channels (h infinity) may be described by a three-state model of the channel with closed, open and inactivated states. A reasonable agreement with the data was obtained when parameters of the inactivated state were supposed to be not changed after aconitine modification of the channels. The membrane repolarization to -70 divided by -110 mV, after long (10 ms) depolarizing shift induces firstly fast current decay ("tail") and then its rather slow increase to a steady-state level. Kinetics of this current requires two or more open states to be postulated. PMID- 6255355 TI - [Kinetics of the reaction between scorpion toxin and the sodium channels of nodes of Ranvier]. AB - The kinetics of the scorpion Buthus eupeus venom toxin binding to sodium channels at holding potential -120 mV and subsequent dissociation of the toxin-channel complex with the membrane potential shifts to -60 divided by +120 mV were studied under voltage clamp conditions in the Ranvier node membrane. The dissociation rate is shown to increase exponentially when shifting the membrane potential towards more positive values, with an e-fold increase for each 32.3 mV. The results are consistent with the suggestion that the dissociation of the toxin channel complex is due to a difference in electric energy between normal and toxin-modified inactivated sodium channels. PMID- 6255356 TI - [Features of the postsynaptic potentials and ion currents in synapses of fast and slow rat muscle fibers]. AB - The time course of spontaneous miniature end-plate potentials (MEPP) and currents (MEPC) was compared in fast and slow muscle fibres using extracellular focal recording or voltage-clamp technique. The mean values of the rise and decline half-time of MEPP and MEPC in slow fibres was 1.3-1.4 times as much as those in fast ones. A smaller difference was observed after AChE inhibition. Decay of the end-plate currents remained generally exponential and its rate depended on the membrane potential level. Distribution of different muscle fibres according to the time course of MEPP and MEPC in fast and slow muscles correlates with the content of the different fibre types identified on other properties. The possible factors controlling the time course of postsynaptic responses (AChE activity, the length of diffusional pathways, differences in the membrane passive electrical properties) and their significance in synapses of different types are discussed. PMID- 6255357 TI - [Postsynaptic potentials of cat neck muscle motoneurons induced by pyramidal tract stimulation]. PMID- 6255358 TI - [Differential diagnosis of ischemic brain infarction and acute necrotizing Herpes simplex encephalitis in elderly patients (author's transl)]. PMID- 6255359 TI - [Variations of 3' 5' cyclic AMP level in CSF after SAH with or without vasospasm (author's transl)]. AB - Levels of 3' 5' AMPc in CSF were analysed by radioimmunoassay in 56 patients. 12 were used as control and 33 had a Subarachnoid Haemorrage (SAH) between 1 and 22 days before sampling. Out of these 33 cases, 20 had an arterial aneurysm, 7 showed a more or less relevant degree of vasospasm on arteriography. 11 other patients presenting different neurological diseases were studied for comparison. (Ischemia, Hydrocephalus, Atrophy, Hematoma). 3' 5' AMPc level in CSF was found to be very low in case of SAH, especially in patients harboring a definite vasospasm. The significance of AMPc level in CSF is discussed in relation with impairment of consciousness, spasm, ischemia, cortical atrophy, hydrocephalus and hematoma. PMID- 6255360 TI - Delayed feedback inhibition of stress-induced activation of pituitary-adrenal function: effects of varying dose, rate and duration of corticosterone administration and of telencephalon removal. PMID- 6255361 TI - Pharmacological evidence of a possible tryptaminergic regulation of opiate receptors by using indalpine, a selective 5-HT uptake inhibitor. PMID- 6255362 TI - Hippocampal distribution of acetylcholine, muscarinic receptors and cyclic GMP. PMID- 6255363 TI - Inhibition of ACH release by prostaglandin E1 in the rabbit superior cervical ganglion. PMID- 6255364 TI - Effects of intrapallidal opiate receptor agonists on striatally evoked head turning. PMID- 6255365 TI - A synthetic ACTH4-9 analogue )Organon 2766) and sleep in healthy man. PMID- 6255366 TI - Sex and strain differences in GABA receptor binding after chronic ethanol drinking in mice. PMID- 6255367 TI - Computed tomography/guided stereotactic surgery: conception and development of a new stereotactic methodology. AB - Computed tomography (CT) has become the first modality to provide the patient's self-brain map for stereotactic neurosurgery. This paper describes our development of a nearly artifact-free stereotactic frame designed for CT imaging. The surgical procedure is performed within the CT scanner itself. The scanner's computer, via a new software program, spatially integrates the new stereotactic frame with the CT images of the patient and with the scanner gantry to provide rapid coordinate determinations, calculate potential probe trajectories, obtain target accuracy within 1 mm, and observe for any procedural complications. Our initial clinical experience with this system is described. PMID- 6255368 TI - Survival in glioblastoma: historical perspective. AB - The accumulated retrospective experience with glioblastoma multiforme was reviewed. Data were extracted from 17 reports in the literature, comprising 2532 patients. Survival curves were constructed for 1561 selected cases that did not include limited surgery and/or astrocytoma Grade III. The median survival after operation for the 1561 patients was 6 months, and only 7.5% lived 2 years. The survival curve is exponential in shape; calculation of its rate constant as well as extrapolation on a least squares regression line for the semilogarithmic plot of the data both predict 3- and 5-year survival rates of 1.7 and 0%, respectively. Curves were also plotted for patients who were treated by operation alone (6 study groups, 349 cases), operation plus radiation (11 groups, 568 cases), and operation plus radiation plus chemotherapy (5 groups, 146 cases); the median survival times for the three groups were 4, 9.25, and 10 months, respectively. It was concluded that (a) all curves converge at 18 to 24 months, irrespective of treatment; (b) radiotherapy is the decisive treatment during the first 18 months; (c) survival can be predicted by adopting an exponential model; and (d) prospective studies are required to detect the marginal benefits of current therapies. PMID- 6255369 TI - Electrophysiological characteristics of crayfish inhibitory. AB - Parameters of IPSPs and characteristics of inhibitory neuromuscular transmission in the dactylopodite-opener muscle of the crayfish pincer at various rhythms of activity were studied by intracellular recording. The presynaptic conduction nature of high-frequency (pessimal) blockade of the inhibitory system was demonstrated. Transformation of the rhythm of stimulation correlated with a decrease in conduction velocity along the inhibitory axon and (or) its branches. At high frequencies of stimulation the mean quantum composition of IPSPs of the potentiation plateau before the beginning of rhythm transformation was lower than at lower frequencies. No signs of exhaustion of mediator reserves were found in the course of high-frequency activity. It is concluded that the mechanism of secretion of inhibitory mediator is more reliable than the function of conduction of the presynaptic nervous impulse. The possible functional significance of the comparatively low reliability of function of crustacean nerve fibers is discussed. PMID- 6255370 TI - Selective depression of neuronal excitability during habituation. PMID- 6255371 TI - Ultrastructural pathology of skin biopsy and fibroblast enzyme studies in a case of GM2-gangliosidosis with deficient hexosaminidase A and thermolabile hexosaminidase B. AB - A 2 year-old non-Jewish boy had muscle hypertonia, a black cherry spot, dementia, and seizures. His skin biopsy showed membranous cytoplasmic bodies in axonal terminals and zebra body-like inclusions in Schwann cells. Biochemically, a deficiency of Hex A and two separate Hex B peaks indicated a type 1 (B variant, Tay Sachs) like subvariant of GM2-gangliosidosis. PMID- 6255372 TI - Retinal benzodiazepine receptors are destroyed by kainic acid lesions. AB - [3H]Diazepam binds to preparations of membranes from chicken retina. Two binding sites were detected; a high affinity site (KD, 1.8 nM and Bmax, 0.17 pmol/mg retina protein) and a low affinity site (KD, 132 nM and Bmax, 1.46 pmol/mg retinal protein). GABA stimulated [3H]diazepam binding to these retinal membranes. One week after injection of kainic acid into the eye, which destroys the horizontal and amacrine cells of the retina, the low affinity site disappeared, while the level of the high affinity site was hardly affected. These results establish that chicken retina contains benzodiazepine receptors, which are closely associated with GABA receptors. The benzodiazepine receptors are probably associated with horizontal and/or amacrine cell synapses which use GABA as a transmitter. PMID- 6255373 TI - Effects of neuronal activity on kainic acid neurotoxicity in the ventral cochlear nucleus. AB - Kainic acid was injected into the brain stem of adult guinea pigs, and the animals were either placed in a sound reducing-chamber or stimulated with 90 dB noise. The pattern and rate of kainic acid-induced degeneration in the anteroventral cochlear nucleus (AVCN) of sound-deprived animals was similar to that in animals exposed to ambient noise [2]. The amount of degeneration was greatly increased in animals stimulated with 90 dB noise. Therefore, although decreased activity in primary auditory fibers does not protect neurons in the AVCN from kainate-induced neurotoxicity, increased auditory stimulation augments the effects of kainic acid in the cochlear nucleus. PMID- 6255374 TI - Effect of calcium removal on thermosensitivity of preoptic neurons in hypothalamic slices. AB - Extracellular single-unit activities of thermosensitive neurons were recorded from the medial preoptic area in rat's hypothalamic slices in vitro. Of 256 preoptic units, 74 were warm-units which increased firing rates in response to a rise in slice temperature and 16 units were cold-units having the opposite type of thermosensitivity. Eighteen of 23 warm-units and 3 of 4 cold-units retained their thermosensitivities during perfusion with Ca2+-free/high Mg2+ salt solution. The thermosensitivities of the remaining 5 warm-units were reversibly abolished in the Ca2+ deficient medium. The results suggest that some warm- and cold-sensitive neurons in the medial preoptic area have an inherent thermosensitivity. PMID- 6255375 TI - The response of dorsal horn neurones of the cat to intraarterial bradykinin and noxious radiant heat. AB - In chloralose-anaesthetized or decerebrate cats intra-arterially administered bradykinin (BKN) and noxious radiant heat were tested on dorsal horn neurones characterized according to their responses to natural stimuli. Of the 28 neurones which were excited only to non-noxious forms of stimuli, BKN affected 4 while noxious radiant heat was ineffective. BKN also affected relatively few of the nociceptor-driven neurones (18 of 60) and most of these were inhibited, while noxious radiant heat excited the majority of these cells (47 of 60). Therefore, under our experimental conditions, noxious radiant heat would appear to be a more effective and specific noxious stimulus than BKN. PMID- 6255376 TI - Neuronal (Na+,K+)-ATPase and the release of purines from mouse and rat cerebral cortex. AB - Slices of mouse or rat cerebral cortex were incubated with [3H]adenine or [3H]adenosine, and [14C]GABA. Purines and GABA could subsequently be released by ouabain. The release of purines previously shown to occur on restoring elevated K+ levels to normal was not mimicked by noradrenaline at concentrations which activate (Na+,K+)-ATPase. Potassium-free solutions evoked no release of purine during the test period, but resulted in a large release when K+ was restored to normal. K+-free solutions evoked an immediate release of GABA. It is concluded that (Na+,K+)-ATPase is not involved in purine release. PMID- 6255377 TI - Selectivity in synaptic changes caudal to acute spinal cord transection. AB - The amplitude of monosynaptic EPSPs produced by the action of single semitendinosus (ST) Ia afferent fibers in ST motoneurons display little or no increase in amplitude within hours of a spinal cord transection performed at the thirteenth thoracic segment. This finding is in marked contrast to results obtained at the medial gastrocnemius (MG) Ia fiber-motoneuron synapse, where EPSPs have been shown to be enlarged, even in preparations with normal ST EPSPs. The increase in EPSP amplitude reported previously at the MG Ia-motoneurons synapse is selective and therefore is probably not a direct consequence of injury to the isolated segment of the spinal cord. PMID- 6255378 TI - Effect of denervation on the endogenous phosphorylating activity in the cytosol of rat skeletal muscle. AB - An endogenous phosphorylating activity is demonstrated in the cytosol from soleus muscle of the rat which is markedly stimulated after severing the motor nerve fibers to this muscle. The [gamma-32P]AT[ phosphotransferase reaction is heat labile, dependent upon Mg2+ but not Ca2+ or cyclic GMP, inhibited by a cyclic AMP dependent protein kinase inhibitor, and directly related to the amount of cytosolic protein which provides the endogenous source of both the protein kinase enzyme, ATP, cyclic AMP and phosphorylatable protein substrate. The time-course of the delayed transitory stimulation of the cytosolic phosphorylating activity of the denervated soleus may involve neurotropic factors. PMID- 6255379 TI - Selectivity of a series of clonidine-like drugs for alpha 1 and alpha 2 adrenoceptors in rat brain. PMID- 6255380 TI - Neuroleptic suppression of feeding and oral stereotypy following microinjections of carbachol into substantia nigra. AB - A large dose of carbachol (5 micrograms/0.5 microliters) unilaterally microinjected into the rostral substantia nigra of rats induced stereotypy characterized by biting, gnawing and licking. A lower dose (0.5 micrograms/0.5 microliter) of the cholinomimetic potentiated normal food intake in satiated animals. Both the cholinergically induced feeding and stereotypy were severely attenuated by subcutaneous administration of haloperidol 0.4 mg/kg. This particular dose of neuroleptic had no significant effect on locomotor activity. These data are consistent with the hypothesis that cholinergic neurotransmission in the rostral substantia nigra mediating oral responses is afferent to the dopamine systems arising from this area. PMID- 6255381 TI - Studies on the extent of dietary fiber intake in West Germany. AB - By means of food diaries the volume of the average daily crude fiber and dietary fiber consumption and the percentage contribution of various groups of plant foods to the total dietary fiber consumption was determined in a group of 150 healthy subjects (89 males and 61 females) from four different occupational groups. It thus became apparent that the mean daily dietary fiber consumption was 22.0 +/- 5.5 g in the artisians and workers of a large industrial plant (group I), 24.8 +/- 8.4 g in students (group II), 21.7 +/- 5.5 g in teachers (group III), and 17.6 +/- 7.7 g in administrative employees (group IV). In groups I-III the mean daily dietary fiber consumption was significantly higher than in group IV. In 17% of the subjects, the mean daily dietary fiber consumption was < 15 g. The mean dietary fiber intake per 1,000 kcal (4.18 MJ) in groups II and III, 8.5 +/- 1.5 and 8.8 +/- 2.2 g, respectively, was significantly higher than in group I with a mean fiber intake of 7.2 +/- 1.4 g. PMID- 6255382 TI - Na+,K+-ATPase in developing rat brain during undernutrition. AB - Na+,K+-ATPase was studied in developing rat brain during undernutrition. The activity of Na+,K+-ATPase was significantly lower in animals that were undernourished from 6 to 17 days after birth than in well-nourished controls. The decreased activity of the enzyme was partially recovered after 4 weeks of rehabilitation. No change in the cation contents of brain following undernutrition was observed. The decrease in Na+,K4-ATPase activity was possibly due to the reduction in cholesterol contents and could be responsible for the observed functional changes associated with malnutrition or undernutrition during development. PMID- 6255383 TI - The effect of various cholecalciferol-related substances on the biosynthesis of the cholecalciferol-dependent calcium-binding protein in the small intestine of the rachitic chick and its relation to rickets. AB - Rachitic chicks were injected with different dose-levels of cholecalciferol and several cholecalciferol-related substances, i.e., dihydrotachysterol 3, ergocalciferol, 5,6-transcholecalciferol and 25-hydroxycholecalciferol. The response to treatment was assayed by the amount of cholecalciferol-dependent calcium-binding protein produced in the mucosa of the small intestine. The biological activity of these substances in the healing of rickets in the rat was also estimated except for ergocalciferol. The relative potencies in stimulating calcium-binding protein production were: 25-hydroxycholecalciferol > cholecalciferol > 5,6-trans-cholecalciferol > ergocalciferol > dihydrotachysterol 3. PMID- 6255384 TI - Influence of cholecalciferol on tissue zinc homeostasis in the rat. AB - A role for calciferol in zinc homeostasis was investigated by radioisotope uptake and compartmental analysis techniques. cholecalciferol was injected into rats 4-5 days prior to radioisotopic study of rapidly exchangeable pools (< 4 h). Kidney, liver, and duodenum had significant increases in zinc uptake rates. Bone and skeletal muscle had significant decreases. No other tissues had significant differences. Compartmental analysis models generated by the SAAM-25 digital computer program suggested a decrease in the fractional tissue to plasma coefficient to be the mechanism for the observed changes in the serum zinc concentration and tissue zinc accumulation rates. It is not clear whether this is a specific effect of calciferol on zinc homeostasis or is a nonspecific response which may reflect some role for zinc in calciferol metabolism. PMID- 6255385 TI - Immunologic identification of papillomavirus antigen in condyloma tissues from the female genital tract. AB - Paraffin sections of condylomata acuminata removed from the lower genital canal were stained for papillomavirus antigen by th peroxidase-antiperoxidase test using a broadly cross-reactive antiserum. The antiserum was prepared by immunization of a rabbit with disrupted capsids of papillomavirus purified from a pool of plantar warts. Specific staining was seen as a brown granular reaction in the nuclei of the epithelial cells; this reaction occurred most consistently in the more superficial cells. Papillomavirus antigen was demonstrable in about half of the 50 specimens examined. The antigen was found in both flat and papillary lesions from the vulva, vagina, and cervix. The distribution of the antigen was widely variable and ranged from abundant in some specimens to patchy and sparse in others. In papillary lesions, antigen-positive cells were found characteristically at the tips of the epithelial fronds. The ability to detect the viral antigen in genital condylomas may help in understanding the pathogenesis of these lesions and in evaluating the role of papillomaviruses in th etiology of lower genital tract cancer. PMID- 6255387 TI - A model for estimation of human exposure to endogenous N-nitrosodimethylamine. AB - A simple mathematical model is formulated to estimate the order of magnitude of the flux of N-nitrosodimethylamine, based upon blood concentrations and the assumption of a quasi steady state between formation and metabolism. The model predicts a total daily exposure which corresponds to an extrapolated risk well within the observed risk for liver cancer in the USA. The ramifications of this model are significant for cancer prevention and for the development of techniques of risk extrapolation. PMID- 6255386 TI - Pregnancy in hypothalamic hypopituitarism. AB - Pregnancy in hypopituitarism is distinctly rare. The authors have recently seen a 26-year-old white woman who had amenorrhea. Endocrine evaluation demonstrated hypogonadotropic hypogonadism, decreased adrenocorticotropic hormone reserve, and low normal thyroid function. The patient, treated with estrogen replacement for a few cycles and with physiologic doses of hydrocortisone, spontaneously conceived and delivered a premature infant. The circumstantial evidence favored the occurrence of a spontaneous ovulation. The possibility that prior administration of cyclic estrogens and/or physiologic doses of cortisone facilitated gonadotropin release and subsequent ovulation remains unclear but cannot be completely excluded. The onset of premature labor may have been related to hypofunction of the anterior pituitary. PMID- 6255388 TI - Human relevance: epidemiology and occupational exposure. AB - This paper reviews briefly some industrial applications which may result in occupational exposure of the workforce to preformed N-nitroso compounds. It considers exposure to nitrate in more detail, discussing epidemiological evidence which lends support to the hypothesis that high nitrate ingestion is related to high mortality from gastric cancer, through the formation in vivo of carcinogenic N-nitroso compounds. It presents the preliminary findings in a census-based mortality study of industrial workers exposed to nitrate-containing dust in the manufacture of fertilizers. PMID- 6255389 TI - Observations on the synthesis of carcinoembryonic antigen by an established human colonic carcinoma cell line. AB - Some properties and kinetics of synthesis of the carcinoembryonic antigen (CEA LoVo) produced by an established human colon carcinoma cell line were analyzed. CEA-LoVo was assayed by the method of Chu and Reynoso which was standardized against the activity of the First British Standard for CEA. CEA-LoVo was stable at -20 and 4 degrees C. At 37 degrees C, CEA-LoVo degraded at the rate of 1.4%/day in cell-free supernatants, and at the rate of 6.6%/day in the supernatants of monolayer cultures. CEA-LoVo was sensitive to enzymatic treatment with trypsin (approximately 55% loss)) and extraction of PCA (> 70% loss). The elution profile of CEA-LoVo in Concanavalin A-Sepharose B coincided with that of the First British Standard for CEA. No A or B blood group antigenic activity was noted. Studies employing immunofluorescent and horseradish peroxidase-labeled antibody techniques demonstrated heavy membrane and moderate intracytoplasmic localization. The greatest amount of net synthesis occurred for cells in the stationary phase while CEA-LoVo release occurred maximally in the lag phase. PMID- 6255390 TI - Effects of theophylline treatment on mouse B-16 melanoma cells in vitro. AB - The effects of theophylline treatment on mouse B-16 melanoma cell growth, metabolism, and membrane antigen expression in vitro were studied. Theophylline treatment inhibited DNA synthesis and the cell growth rate, and caused an elevation of intracellular cAMP levels. Cells treated with theophylline became elongated and assumed a normal fibroblast-like morphology. Theophylline treatment of B-16 cells also reduced the levels of tumor specific antigen and H-2 antigen detectable on the cell membrane. PMID- 6255391 TI - [Uterine response of golden hamsters to estrogenic stimulation in postnatal ontogeny]. AB - The proliferative activity of the cells of uterine epithelium and stroma of the developing golden hamsters and the activity of acid phosphatase isozymes in these tissues was studied. The dynamics of changes of these indices during the normal development and upon estrogenic stimulation was followed. The uterine cells were shown to react to estrogenic stimulation was followed. The uterine cells were shown to react to estrogenic stimulation by the increase of proliferation from the first days of postnatal development. Characteristic changes in the ratio of the acid phosphatase isozymes in the epithelial cells in response to estrogenic stimulation appeared in the 2nd week of postnatal development only. The definite level of differentiation of cells-targets appears to be indispensable for the realization of certain specific effects of the hormone. PMID- 6255392 TI - The effect of natural and artificial light via the eye on the hormonal and metabolic balance of animal and man. AB - Color change of the plaice and frog, and development of the testes in duck are induced by light stimuli via the eye. Eliminating experiences on the frog (Hollwich) and on the duck (Benoit) showed that these stimuli-beside vision-use a separate way, the so-called 'energetic portion' of the visual pathway (Hollwich). In compared studies on blind and on temporarily blind patients involved by cataract in both eyes, we found significant low levels of ACTH and cortisol. The levels normalized after cataract extraction. -Furthermore, we studied the influence of strong artificial illumination (3,500 and 3,200 lx) on healthy persons with considerable and, on the other hand, with minimal difference of their spectral composition to daylight. We found stress-like levels of ACTH and cortisol in the first group. These findings explain the agitated mental and physical behavior of children staying the whole day in school under artificial illumination with strong spectral deviation from daylight. Therefore, to avoid mental and physical alterations, the spectrum of artificial illumination should be largely similar to that of natural light. PMID- 6255393 TI - A case of the cryptophthalmos syndrome. AB - A case of the cryptophthalmos syndrome is presented, showing bilateral absence of separate eyelids and of the palpebral fissure, the facial skin being continuous over both eyes. Low set ears, marked syndactylies, absence of the urinary tract and external genital hypertrophy were noted, while laryngeal atresia allowed a survival of 5 min only at birth. Histopathological study showed the absence of the conjunctiva, and the ectopic lens surrounded by coarse connective tissue in both eyes. The eyes showed a single chamber: no normal corneal elements, iris or anterior chamber were identifiable and the ciliary body was abnormal. An excessive vascularisation of the peripheral retina and a subretinal deposit of lenticular bladder cells were additional features. The karyotype was that of a normal female. PMID- 6255394 TI - [Acute Burkitt-cell B type lymphoid leukemia]. PMID- 6255395 TI - The etiology of nasopharyngeal cancer and its management. AB - In dealing with the nasopharyngeal cancer problem, we find a fascinating pathologic entity, which acts in a varied fashion depending on the ethnic origin of the patient with a possible genetic basis for its etiology. More recently we have become aware of the possible etiology, i.e., the role of the Epstein-Barr virus in cancer of the nasopharynx. The earlier the diagnosis is made, in view of the present radiotherapeutic advances, the greater the possibility of increasing the cure rate in this disease. PMID- 6255396 TI - Surgery for glomus tumors at the skull base. AB - Glomus tumors of the temporal bone frequently involve the skull base. In the present study, 34% of the tumors occurred with cranial nerve palsies and 15% invaded the CNS. The procedure for surgical resection of glomus tumors of the skull base is described. Results of the procedure included successful surgical resection of 80% of the glomus jugulare tumors and of 94% of the glomus tympanicum tumors. Tumor recurrence and persistence occurred only in the patients with CNS invasion. PMID- 6255397 TI - Glomus jugulare tumor surgery with intracranial extension. AB - Total surgical excision of a glomus jugulare tumor is the treatment of choice for this benign tumor. If the tumor has extended beyond the temporal bone into the intracranial spaces, most often the posterior fossa, the surgical excision becomes more difficult. If the tumor has extended anteriorly and posteriorly into the posterior fossa or if a portion of the tumor is exposed in the external auditory canal with the concurrent infection that is seen with this presentation, the intracranial portion of the tumor should be removed as a first step in a planned two-stage removal of the tumor. If the intracranial extension is limited and there is no infection present with the tumor, a combined otologic neurosurgical approach using transtemporal and suboccipital access to the temporal bone will allow successful total removal of the tumor in a one-stage procedure. Details are presented to demonstrate this combined otologic and neurosurgical approach to large glomus tumors with intracranial extension. PMID- 6255398 TI - Surgical therapy of internal carotid artery lesions of the skull base and temporal bone. AB - Five cases of carotid artery lesions at the skull base or temporal bone, treated surgically, are presented. These lesions include mycotic aneurysms and carotid stenosis secondary to angiofibroma and a glomus caroticum. One case demonstrated an anomalous carotid anatomic pattern with a persistent stapedial artery. A description is provided of the technique of subtotal petrosectomy with permanent anterior displacement of the facial nerve, and middle ear obliteration, thus achieving a safe exposure of the temporal course of the internal carotid artery. The cases indicate that cooperation between temporal bone surgeons and vascular surgeons is a prerequisite to successful repair of such lesions, as good recovery in all five cases was achieved. The techniques allow maintenance of carotid flow during and after repair, reducing the potential for neurologic complications or mortality. PMID- 6255399 TI - Immunopathology of infectious mononucleosis and other complications of Epstein Barr virus infections. PMID- 6255400 TI - Morphologic and functional aspects of hormone-producing tumors. PMID- 6255401 TI - The myofibroblast. PMID- 6255402 TI - [Oxidative enzyme activity in the gastric mucosa in gastroduodenitis in children]. PMID- 6255403 TI - [Undifferentiated carcinoma of the nasopharynx associated with the Epstein-Barr virus. Diagnostic value of EBV serology]. PMID- 6255404 TI - [Disulfiram-induced peripheral neuropathies (author's transl)]. AB - A 28-year-old woman experienced a confusional attack with hallucinations associated with moderate motor deficiency of the lower limbs during treatment with disulfiram 1 g/day. Later on, a temporary increase in disulfiram dosage to 1.75 g/day was followed by quadriplegia and paralysis of the facial and glosso pharyngeal nerves. Paralysis regressed rapidly in the cranial and upper limb areas, but very slowly in the lower limbs. Disulfiram-induced peripheral neuropathies are not uncommon. They may take various forms, such as optic neuritis, polyneuritis of the limbs and, exceptionally, severe multiple paralysis with psychic disorders, as in the case reported here. PMID- 6255405 TI - [Changes in cyclic adenosine monophosphate after vagotomy]. PMID- 6255406 TI - Extensive diversity among Drosophila species with respect to nucleotide sequences within the adenine + thymine-rich region of mitochondrial DNA molecules. AB - Mitochondrial DNA (mtDNA) molecules from species of the genus Drosophila contain a region exceptionally rich in adenine + thymine (A+T). Using agarose gel electrophoresis and electron microscopy, we determined that in the mtDNA molecules of D. melanogaster, D. simulans, D. mauritiana, D. yakuba, D. takahashii, and D. virilis, the A+T-rich regions, which are 5.1, 4.8, 4.6, 1.1, 2.2, and 1.0 kilobase pairs in size, respectively, are at homologous locations relative to various common EcoRI and HindIII cleavage sites. Under conditions highly permissive for base pairing (35% formamide), heteroduplexes were constructed between EcoRI fragments and whole circular molecules of mtDNAs of the above mentioned six species in a variety of combinations. Complete pairing of molecules outside the A+T-rich region was found in all heteroduplexes examined. However, in contrast, A+T-rich regions of the different species failed to pair in all but those combinations of mtDNAs involving the three most closely related species. In heteroduplexes between D. melanogaster and D. simulans, and between D. melanogaster and D. mauritiana mtDNAs, up to 35% of the A+T-rich regions appeared double-stranded. These data indicate that much more extensive divergence of sequences has occurred in A+T-rich regions than in other regions of Drosophila mtDNA molecules. PMID- 6255407 TI - Selective blotting of restriction DNA fragments on nitrocellulose membranes at low salt concentrations. AB - The pattern of restriction DNA fragments transferred from agarose gel to nitrocellulose membranes (Southern's technique) can be affected by the salt concentration of the transfer solvent. PMID- 6255409 TI - A new restriction endonuclease from the anaerobic bacterium, Desulfovibrio desulfuricans, Norway. AB - The purification and characterization of a new restriction endonuclease, Dde 1, from a sulfate-reducing, anaerobic bacterium, Desulfovibrio desulfuricans, Norway, is reported. The enzyme recognizes the sequence (see formula index) and cleaves at the position indicated by the arrows. The enzyme preparation obtained is suitable for restriction mapping an ligation. PMID- 6255408 TI - Nucleotide sequences of heat shock activated genes in Drosophila melanogaster. I. Sequences in the regions of the 5' and 3' ends of the hsp 70 gene in the hybrid plasmid 56H8. AB - We present the sequences at the 5' and 3' ends of one hsp 70 gene variant which is derived from the chromosomal locus 87A7. The 5' end of the hsp 70 mRNA has also been determined. 550 bp upstream from the 5' end of the hsp 70 mRNA, there is a very A+T rich region shown by heteroduplex analysis to be also present at the same position in other hsp 70 genes9. The 5' end of the hsp 70 mRNA was found 26 bp after a characteristic "Hogness box". The first ATG codon was found 250 bp downstream from the 5' end of the hsp 70 mRNA. We also determined the termination codon at the 3' end of the hsp 70 gene. Comparisons with other genes are discussed. PMID- 6255410 TI - The transposable element Mdg3 in Drosophila melanogaster is flanked with the perfect direct and mismatched inverted repeats. AB - MDg3 is a family of mobile dispersed genetic elements represented by 15 copies in the haploid genome of D. melanogaster and flanked, like other similar elements, by the regions of homology. In the present work, these regions of mdg3 have been sequenced. The existence of perfect direct repeats 268 base pairs long has been demonstrated. Inverted repeats are located on the gene distal side of them. It is possible to construct a perfect 8 b.p. palindrome or a slightly mismatched 18 b.p. palindrome. The inverted repeats are flanked by two short 5 b.p. direct repeats. PMID- 6255411 TI - A second site specific endonuclease from Thermus thermophilus 111, Tth111II. AB - A second site specific endonuclease with novel specificity has been purified from Thermus thermophilus strain 111 and named Tth111II. The enzyme is active at temperature up to 80 degrees C and requires Mg2+ or Mn2+ for endonuclease activity. Tth111II cleaves phi X174RFDNA into 11 fragments and lambda NA into more than 25 fragments. From the 5'-terminal sequences of TthlllII fragments of phi X174RFDNA determined by the two dimensional homochromatography and the survey on nucleotide sequence of phi X174RFDNA, it was concluded that Tth111II recognizes the DNA sequence (see former index) and cleaves the sites as indicated by the arrows. PMID- 6255412 TI - Sequence organization of feline leukemia virus DNA in infected cells. AB - A restriction site map has been deduced of unintegrated and integrated FeLV viral DNA found in human RD cells after experimental infection with the Gardner Arnstein strain of FeLV. Restriction fragments were ordered by single and double enzyme digests followed by Southern transfer (1) and hybridization with 32P labeled viral cDNA probes. The restriction map was oriented with respect to the 5' and 3' ends of viral RNA by using a 3' specific hybridization probe. The major form of unintegrated viral DNA found was a 8.7 kb linear DNA molecule bearing a 450 bp direct long terminal redundancy (LTR) derived from both 5' and 3' viral RNA sequences. Minor, circular forms, 8.7 kb and 8.2 kb in length were also detected, the larger one probably containing two adjacent copies of the LTR and the smaller one containing one comtaining one copy of the LTR. Integrated copies of FeLV are colinear with the unintegrated linear form and contain the KpnI and SmaI sites found in each LTR. PMID- 6255413 TI - Analysis of the secondary and tertiary structures of Rous sarcoma virus RNA. AB - The secondary and tertiary structures of the 35S RNA of Rous Sarcoma virus have been investigated. T1 RNase partial digests have been first resolved into their components by gel electrophoresis under non denaturing conditions and then each component analyzed further by various techniques. More than one hundred structured fragments have thus been isolated and shown to consist of several individual nucleotide sequences located far apart on the genome. On the basis of the results, a cloverleaf model for the structure of RSV 35S RNA is proposed that has implications for the various biological functions of this RNA. PMID- 6255414 TI - Saccharomyces cerevisiae plasmid, Scp or 2 mum: intracellular distribution, stability and nucleosomal-like packaging. AB - Cell fractions from yeast strains known to harbor the plasmic 2 mum or Scp were treated with nucleases used to probe eukaryotic chromosome structure. Scp and subfragments were identified by hybridization to natural or cloned Scp probes according to Southern (34). Specificity was confirmed with non-Scp probes. Copy/haploid nuclear genome(n) was estimated from reconstructions at a resolution of 0.5/n. About 43-67% of the total cellular copy exists as nucleoprotein complexes which separate from other debris on isokinetic sucrose gradients with s values of 67-110. These complexes are totally degraded by DNAase I. Digestion with micrococcal nuclease produced integral-sized fragments; they are not generated by direct mixing of pure Scp with nuclear chromatin from a[cir] strain. Initial digests gave a repeat of 168 +/- 3 base pairs (bp) for both Scp and nuclear nucleoprotein; advanced digests reduced the nuclear repeat relative to Scp by 8 bp. Of a potential 37 repeat units/plasmid, 31-32 were directly measured. A strain difference in Scp autodegradation was found. A partial nuclease resistant form was also demonstrated whose abundance was cell strain and growth stage dependent. Both Scp isomers exist in these complexes which are structurally similar to simian viral 40 minichromosomes. PMID- 6255415 TI - The extraction by micrococcal nuclease of glucocorticoid receptors and mouse mammary tumor virus DNA sequences is dissociated. AB - Glucocorticoid receptors (RG) and mammary tumor virus (MM-TV) DNA sequences were extracted by micrococcal nuclease digestion from the nuclei of C3H mouse mammary tumor cells in order to specify their relative distribution in chromatin. RG was labelled and translocated into the nuclei by incubating cells with 3H Dexamethasone (3H Dex). The purified nuclei were then treated at 2 degrees C with micrococcal nuclease. Three chromatin fractions were successively obtained: an isotonic extract (ne3H1), ahypotonic extract (ne2) and the residual pellet (P). The Dex-RG complexes were measured by the hydroxyapatite technique. The MMTV DNA sequences were titrated by molecular hybridization with an excess of MMTV radioactive cDNA probe. Up to 75% of the nuclear 3H Dex and the MMTV radioactive cDNA probe. Up to 75% of the nuclear 3H Dex and MMTV DNA sequences were extracted in a concentration dependent manner while only 10-15% of nucleic acids became soluble in 10% perchloric acid. The extracted 3H Dex-RG complex was found to be partly bound to soluble chromatin and partly free. The free complex displayed similar sedimentation constants (4S, 7S) and DNA binding ability to the cytosol receptor. The 3H Dex-RG complexes were 2 to 8 fold more concentrated in ne1, which is known to be enriched in active chromatin, than in ne2. Conversely, the concentration of MMTV DNA sequences per microgram DNA was the same in the three nuclear fractions. These results suggest that the Dex-RG complexes are concentrated in an active fraction of chromatin. We propose that, among the 20-30 copies of MMTV genes per haploid genome, only a small proportion are transcribed or regulated. PMID- 6255416 TI - The organisation of the long range periodicity calf satellite DNA I variants as revealed by restriction enzyme analysis. AB - The analysis of a large number of restriction sites within the long range periodicity calf satellite DNA I does not reveal a superimposable shorter repeat. Although some restriction sites are present in almost all the 100,000 tandemly arranged copies of the 1460 bp repetition unit, other sites such as Atu CI occur at much lower frequencies. When present they are distributed randomly along the satellite DNA molecules. The missing sites appear to result from random and presumably single base alterations. Digestion with the enzymes Hha I and Kpn I showed another type of variant to exist within the calf satellite DNA I. Unlike Atu CI the distributions of the variants detected by these enzymes are not random and organised on long stretches of satellite DNA. The possible functional significance and evolutionary implication of these results are discussed. PMID- 6255417 TI - The distal end of the ribosomal RNA operon rrnD of Escherichia coli contains a tRNA1thr gene, two 5s rRNA genes and a transcription terminator. AB - The distal region of the Escherichia coli ribosomal RNA operon rrnD has been sequenced to identify transfer RNA genes which might be contained within this transcriptional unit, and to define a possible transcription termination site. A nucleotide sequence corresponding to the gene for tRNA1thr is located between two genes for 5S rRNA. The spacer region between the proximal 5S rRNA gene and the tRNA1thr gene is 12 base pairs long, whereas the spacer region between the distal 5S rRNA gene and the tRNA1thr gene is 37 base pairs. Possible sites for RNA processing are discussed, and the sequence of the tRNA1thr gene is found to possess the same anticodon as the tRNA3thr gene. A putative transcription termination site for rrnD was located about 25 base pairs distal to the 3' end of the second 5S rRNA gene. The rrnD and rrnC terminators are compared with each other and with other prokaryotic terminators. Located at exactly the same site on the complementary strand is another putative transcription termination site for a gene being transcribed towards rrnD. The possibility of overlapping terminators is discussed. PMID- 6255419 TI - The 5'-cytosine in CCGG1 is methylated in two eukaryotic DNAs and Msp I is sensitive to methylation at this site. AB - Novikoff rat hepatoma and bovine liver DNAs were digested with Msp I or Hpa II. Restriction fragments were end-labeled using [alpha-32P]-dCTP and the Klenow fragment of E. coli DNA polymerase I and then digested to 2'-deoxyribonucleoside 3'-monophosphates using micrococcal nuclease and spleen phosphodiesterase. Mononucleotides were separated by two-dimensional thin layer chromatography, localized by radioautography, and the [32P]-label quantitated by scintillation spectrometry. This method, based on known specificities of Msp I and Hpa II, shows that CCGG, CMGG, and MCGG (M refers to 5-methylcytosine) occur at frequencies of 89.6%, 1.4%, and 9.0%, respectively, in the rat DNA and at 41.6%, 48.3%, and 10.0%, respectively, in the bovine DNA. [32P] recovery in 3'-5-MedCMP from end-labeled Msp I digests was negligible compared to recovery from Hpa II digests. Hence, Msp I is sensitive to methylation at the 5' cytosine in the sequence CCGG. PMID- 6255418 TI - Sequence of the distal tRNA1Asp gene and the transcription termination signal in the Escherichia coli ribosomal RNA operon rrnF(or G). AB - Several DNA fragments carrying tRNA genes have been cloned from EcoRI endonuclease digests of Escherichia coli DNA. Using cloned DNA, the sequence of the region around the distal gene for tRNA1Asp (F(or G)) in the E. coli ribosomal RNA operon [rrnF(or G)] has been determined. In the distal portion of rrnF(or G), the genes for 23S, 5S rRNA and tRNA1Asp (F(or G)) are located in that order and separated by intergenic spacers of 93 and 52 base pairs, respectively. A possible hairpin structure, with its center between the 22nd and 23rd base pair downstream from the 3'-end of the tRNA1Asp(F(or G)) gene, followed by a sequence of eight thymidine residues was identified as the transcription termination signal for rrnF(or G). The termination is rho-independent, at least in vitro, and occurs within the region of the contiguous thymidine residues. A possible promoter for a protein gene is present about 50 base pairs downstream from the rrnF(or G) terminator. PMID- 6255420 TI - Post-transcriptional modification of the poly(A) length of galactose-1-phosphate uridyl transferase mRNA in Saccharomyces cerevisiae. AB - Thermal elution poly(U)-Sepharose chromatography was utilized to fractionate yeast mRNA based on poly(A) size. Analysis of the in vitro translation products of the fractionated RNAs in a wheat-embryo cell-free protein synthesis system shows a heterogeneous but equal distribution of these abundant translatable mRNAs in the different poly(A) size classes. By comparing the translational activity of inducible galactose-1-phosphate uridyl transferase mRNA, which can be monitored as a function of age, to contitutive mRNAs, we demonstrate that initially galactose-1-phosphate uridyl transferase mRNA has a uniformly large poly(A) tail which becomes heterogeneous and shorter with age in the cytoplasm. These observations are consistent with the previously observed cytoplasmic poly(A) catabolism in yeast and with cytoplasmic post-transcriptional modification of the poly(A) length of galactose-1-phosphate uridyl transferase mRNA. PMID- 6255421 TI - DNA gyrase subunit stoichiometry and the covalent attachment of subunit A to DNA during DNA cleavage. AB - Escherichia coli DNA gyrase contains a 1:1 ratio of protomers coded by the genes gyrA and gyrB. This along with previous results shows that the enzyme has two copies of each protomer and thus a molecular weight of 400,000. Abortion of the gyrase reaction results in double-strand breakage of the DNA and covalent attachment of both gyrA protomers to the 5'-cut ends. We conclude that the gyrA protomer contains a critical part of the active site for the concerted breakage and reunion reaction of gyrase, the topoisomerase activity of the enzyme. PMID- 6255422 TI - Complete nucleotide sequence of mouse immunoglobulin mu gene and comparison with other immunoglobulin heavy chain genes. AB - We have determined the complete nucleotides sequence (2168 bases) of the immunoglobulin mu gene cloned from newborn mouse DNA. The cloned 13kb fragment contained the entire constant region gene sequence that is interrupted by three intervening sequences at the junction of domains as previously shown in the gamma 1, gamma 2 b and alpha genes. The amino acid sequence predicted by the nucleotide sequence agrees with that of the mu chain secreted by a myeloma MOPC104E except for 8 residues out of 448 residues. The homologous domains of the mu, gamma 1 and gamma 2b genes are more similar to each other than the different domains of the mu genes are. The result implicates that the class of the immunoglobulin heavy chain genes diverged after the heavy chain genes established the multi-domain structure. The short intervening sequences of the mu and gamma genes are more conserved than the coding sequences except for the COOH-terminal domains. The results implicate that the nucleotide sequence of the intervening sequence is under selective pressure, possibly to maintain a secondary structure of the nuclear RNA to be spliced. PMID- 6255423 TI - E coli RNA polymerase-rRNA promoter interaction and the effect of ppGpp. AB - The interaction between RNA polymerase and the E coli r (ibosomal) RNA promoters of the rrnX and rrnE operon was studied with the filter-binding technique. Quantitative differences were observed between the rrnX and rrnE promoters: stable rrnX promoter complexes are formed faster, and are less sensitive towards heparin and salt than stable rrnE promoter complexes. The effect of ppGpp, the specific inhibitor of rRNA synthesis, on rrn promoter complex formation was studied. In the presence of ppGpp complexes are formed which cannot be trapped in a transcription complex by addition of the start nucleotides, and are therefore considered to be non-productive. A tentative mode for the action of ppGpp is proposed. PMID- 6255424 TI - A novel type of secondary modification of two CCGG residues in the human gamma delta beta-globin gene locus. AB - The majority of the CCGG residues in the human gamma delta beta-globin gene locus are cleaved by Msp I, irrespective of the tissue of origin of the DNA, although these sites show differential sensitivity to Hap II as a result of methylation of the internal C residue of the cleavage site (ref 6). Two CCGG sites, at homologous positions 54 nucleotides in front of the G gamma- and A gamma-globin genes respectively, are not cleaved by Msp I in DNA from several human tissues, although DNA from placenta, foetal liver and from some established cell lines is cut at these sites. We have cloned the A gamma-globin gene from foetal blood DNA where the relevant CCGG site is not cut by Msp I. After cloning, the CCGG site can be cut by Msp I. The failure to cleave at this CCGG site in foetal blood DNA therefore, is not the result of a change in the DNA sequence of the cleavage site. Most likely the external C residue and perhaps both C residues are blocked by methylation at these two specific sites. PMID- 6255425 TI - Characterization of cloned ribosomal DNA from Drosophila hydei. AB - The structure of ribosomal genes from the fly Drosophila hydei has been analyzed. EcoRI fragments, cloned in a plasmid vector, were mapped by restriction enzyme analysis. The lengths of the regions coding for 18S and 28S rRNA were defined by R-loop formation. From these data a physical map of the rRNA genes was constructed. There are two major types of rDNA units in D. hydei, one having a size of 11 kb and the other a size of 17 kb. The 17 kb unit results from an intervening sequence (ivs) of 6.0 kb, interrupting the beta-28S rRNA coding region. Some homology between th D. hydei ivs and D. melanogaster type 1 ivs has been described previously (1). However, the restriction sites within these ivs show considerable divergence. Whereas D. hydei rDNA D. melanogaster rDNA, the nontranscribed spacer has little, if any, sequence homology. Despite difference in sequence, D. hydei and D. melanogaster spacers show structural similarities in that both contain repeated sequence elements of similar size and location. PMID- 6255427 TI - Histone 2B can be modified by the attachment of ubiquitin. AB - Histone 2B in mouse and man can be modified by the post-translational addition of ubiquitin. In mouse L1210 cells, both H2B variants are modified, however only to the extent of 1-1.5% compared with about 11% of H2A. Analysis of cyanogen bromide peptides shows that ubiquitin is attached to the C-terminal part of the histone. PMID- 6255426 TI - Accessibility of expressed and non-expressed genes to a restriction nuclease. AB - Nuclei of mouse liver and an immunoglobulin producing myeloma were digested with HaeIII or its isoschizomer BspRI. The DNA fragment patterns after electrophoresis, blotting, and hybridization were very similar for the two types of nuclei when a probe for the non-expressed beta-globin gene was used. The constant (C) region of the kappa light chain gene, on the other hand, was more accessible to the nuclease in myeloma than on liver nuclei. In myeloma nuclei the BspRI sites were about equally sensitive, in fact the pattern resembled a partial digestion pattern of free DNA. In contrast, in liver nuclei some sites were much more protected than others. This is interpreted by assuming that this single copy non-expressed gene region is covered by nucleosomes which are preferentially located on certain DNA sequences. Restriction nuclease digestion of nuclei seems to be a promising method for the analysis of genes in their expressed and non expressed states. PMID- 6255428 TI - Myeloma with multiple rearranged immunoglobulin kappa genes: only one kappa gene codes for kappa chains. AB - In many myelomas more than one kappa gene is rearranged (2-5). We are reporting here the results of studies undertaken to determine whether all the rearranged genes are expressed. It was found that in the myeloma NS-1 three different rearranged kappa genes exist. In a subline of NS-1 and several hybridomas produced by fusion of mouse spleen cells with NS-1 it was found that production of NS-1 kappa chains was correlated with the presence of one of the three kappa genes. Loss of this "expressed" gene eliminated the synthesis of the NS-1 kappa chains, loss of one of the other two rearranged kappa genes did not. It is hypothesized, that allelic exclusion (20) of kappa genes generally operates by the functional rearrangement of one kappa gene; other rearrangements are relatively frequent, at least in myelomas, but mostly they are nonfunctional and thus scrambled antibody molecules do not arise. PMID- 6255429 TI - Comparison of different rearranged immunoglobulin kappa genes of a myeloma by electronmicroscopy and restriction mapping of cloned DNA: implications for "allelic exclusion". AB - We have studied the organization and function of different rearranged kappa genes in a myeloma, MOPC-21. Two kappa genes were cloned into Charon 4A and compared with each other and with a cloned germline CK gene by restriction mapping and electron microscopy. One MOPC-21 clone corresponds to the gene coding for the MOPC-21 kappa chain polypeptide; it has the V21 gene joined with the CK gene at the J2 sequence. The other MOPC-21 clone corresponds to a nonfunctional rearranged MOPC-21 kappa gene, except for a lkb deletion, 3' of J4. A similar deletion is also found in a "new" kappa gene present in NS-1, a cellular subclone of MOPC-21. The clone of the "nonfunctional" kappa gene has a V gene which is distinct from V21 which is joined to CK in the vicinity of J2. The undeleted form of this gene codes for a KRNA having the size of mature KmRNA which, however, is not translated into kappa chains. Thus the defect of the "nonfunctional" gene manifests itself at a late step of gene expression. The basis for "allelic exclusion" of antibody genes may simply be the complexity of the processes between genes and gene products, resulting in the expression of only one gene. PMID- 6255430 TI - Ordered distribution of modified bases in the DNA of a dinoflagellate. AB - In DNA of the dinoflagellate Crypthecodinium cohnii, 38% of the thymine is replaced by the modified base 5-hydroxymethyluracil, and approximately 3% of the cytosine is replaced by 5-methylcytosine. Both of the modified bases are non randomly distributed in the DNA. Determinations of 3' nearest neighbors show that HOMeU is preferentially located in the dinucleotides HOMeUpA and HOMeUpC. Pyrimidine tract analysis shows that HOMeU is also greatly enriched in the trinucleotide purine-HOMeU-purine. As in other eukaryotes, methylcytosine in C. cohnii DNA occurs predominantly in the dinucleotide MeCpG. By analysis of restriction endonuclease digestion patterns of C. cohnii total DNA and ribosomal DNA, we have found that the central CpG dinucleotides in the sites for the enzymes Hpa II (CCGG) and Hha I (GCGC) are extensively methylated in both total DNA and ribosomal DNA. Results of digestion with Ava I, however, indicated that not all CpG dinucleotides in the sequence CCTCGGAG are methylated in C. cohnii DNA. PMID- 6255431 TI - Inhibition of Eco RI action by polynucleotides. A characterization of the non specific binding of the enzyme to DNA. AB - The cleavage of the plasmid pBR322 by the restriction endonuclease Eco RI has been studied in the presence of various polynucleotides and the double stranded octanucleotide d-(GGAATTCC) in order to clarify whether there is a preferential interaction of Eco RI with DNA sequences other than -GAATTC-. The steady state kinetic analysis shows that all polynucleotides investigated with the possible exception of poly-dG.poly-dC inhibit the cleavage competitively with Ki values in the range of 10(-4) to 10(-5) [M nucleotides]. The Ki of d-(GGAATTCC) is 1.5.10( 6) [M nucleotides], indicating that the specific binding is approx. 2 orders of magnitude stronger than non-specific binding. PMID- 6255432 TI - Identification by nucleotide sequence analysis of a goat pseudoglobin gene. AB - We have recently prepared a recombinant library of goat genomic DNA and have isolated clones containing th known goat globin genes. These include the alpha, gamma, beta C and beta A genes. In addition to these, another beta-like sequence has been observed. In this communication we report the complete nucleotide sequence of this gene, excluding a portion of the large intervening sequence. Several features suggest that this is a non-functional or pseudoglobin gene. The alterations include a frameshift mutation, substitution of the heme-binding histidines, a mutated termination codon, a change in the GT/AG excision sequence of the 5' end of the first intervening sequence, an AT rich sequence in the 3' untranslated region, and a mutated Hogness-Goldberg box. We conclude that this gene cannot function in the synthesis of globin. PMID- 6255433 TI - DNA wrapping in nucleosomes. The linking number problem re-examined. AB - Chromatin was assembled in vitro from relaxed closed circular DNA (SV40) and core histones at histone to DNA ratios of 0.2 to 0.3 (g/g) and incubated with topoisomerase I to relax supercoils in DNA regions not constrained by protein. Addition of histones H1 + H5 to the chromatin at an ionic strength of 0.1 M, in the presence of the solubilizing agent, polyglutamic acid, and topoisomerase I, increased the magnitude of the DNA linking number change, relative to protein free DNA. No change in the linking number distribution occurred for relaxed protein-free DNA under these conditions. Control experiments indicated that the increase in the absolute value of the DNA linking number change in the chromatin could not be attributed to an increase in the number of nucleosomes per DNA molecule. These data suggest a solution to the linking number problem associated with models of chromatin structure. PMID- 6255434 TI - Sequence of 863 nucleotides encompassing the PstI site of the yeast 2 micron plasmid. AB - The sequence of part of the larger unique region of the yeast 2 micron plasmid cloned in pMB9 has been determined. The sequence extends from the single EcoRI site in this region to the AvaI site and includes the single PstI site and HpaI site. A notable feature of this sequence is the presence of tandem repeats of 124 residues beginning at the HpaI site and extending beyond the AvaI site. The sequence was determined independently by both the Maxam-Gilbert procedure applied to isolated restriction fragments, and by the chain-termination procedure applied to restriction fragments cloned in the single-stranded phage M13mp2 and purified by plaque selection. PMID- 6255435 TI - Characterisation of polyoma late mRNA leader sequences by molecular cloning and DNA sequence analysis. AB - The leader sequences of two of the three polyoma virus late mRNAs were characterised by molecular cloning and DNA sequence analysis. A short single stranded DNA fragment complementary to the 5' end of the body of mVP1 was used to prime cDNA synthesis, and double-stranded cDNA was inserted into a derivative of pAT 153. Analysis of fourteen mVP1 cDNAs and two mVP3 cDNAs allowed the precise determination of the leader-body joints, and demonstrated that the majority of polyoma late leader sequences consist of exact tandem repeats of a 57 nucleotide sequence present only once in the genomic DNA at 66-67 m.u. The sequences in the genomic DNA borderline this unit are typical of those found at RNA splice points. Leader sequences contained on average three to four repeat units. Nuclease S1 mapping of total late mRNA demonstrated that most mRNA 5' ends map heterogeneously in the 50 nucleotides 5' to the repeated sequence unit. The structures of the leader sequences strongly suggest that they are generated by appropriate splicing events from a tandemly repeated transcript of the entire circular viral genome. PMID- 6255436 TI - Characterisation of a new alpha thalassemia 1 defect due to a partial deletion of the alpha globin gene complex. AB - A new deletion causing alpha thalassemia has been characterised in a Greek family. Detailed mapping of the alpha gene complex shows that the deletion extends for 5.2 kb and removes the whole of the alpha 2 gene and the 5' end of the alpha 1 gene. The affected chromosome, therefore produces no normal alpha chains and results in a phenotype of alpha thalassemia 1. PMID- 6255437 TI - Two drosophila melanogaster tRNAGly genes are contained in a direct duplication at chromosomal locus 56F. AB - One Drosophila melanogaster tRNAGly gene occurs on each 1.1-2.0 kb unit of a direct duplication at chromosomal region 56F. The nucleotide sequence of the gene and the 5' flanking region has been determined. The non-transcribed strand sequence of the tRNA gene is: 5' GCATCGGTGGTTCAGTGGTAGAATGCTCGCCTGCCACGCGGGCGGCCCGGGTTCGATTCCCGGCCGATGCA 3'. This nucleotide sequence is identical to that of the major glycine tRNA in Bombyx mori posterior silk gland. Within the 22 kb region mapped, additional tRNA genes are found, an observation consistent with reports that genes for other isoacceptors are present at this locus. PMID- 6255438 TI - A comparison of DNA cleavage by the restriction enzymes SalPI and PstI. AB - Methods for obtaining highly active, exonuclease-free, stable preparations of the Streptomyces albus P restriction enzyme SalPI are described. SalPI and its isoschizomer PstI (from the taxonomically distant Providencia stuartii 164) both cleave their recognition sequence (5'-CTGCAG-3') to generate fragments terminating in tetranucleotide 3' extensions whose sequence is 5'-TGCA-3'. Bacteriophage R4G2 DNA, protected against SalPI cleavage by pregrowth on S. albus P, is also protected against PstI cleavage; and total DNA of both S. albus P and P. stuartii 164 is resistant to cleavage by both enzymes. PMID- 6255439 TI - Single-strand DNA binding protein from rat liver: interactions with supercoiled DNA. AB - As shown by competition experiments, the single-strand DNA binding protein from normal rat liver (S25) interacts preferentially with supercoiled DNA compared to relaxed DNA duplexes. When followed both by sedimentation analysis and by nitrocellulose filter assay, the binding of S25 to SV40 supercoiled DNA (FI) appears to be non-cooperative. Saturation is reached at a protein to DNA weight ratio of about 2. The S25-DNA complexes prefixed with glutaraldehyde appear as beaded structures having an average of 14 to 16 beads per SV40 DNA molecules. Cross-linking of S25 bound to SV40 DNA by dimethyl suberimidate allows to detect oligomeric structures containing a maximum of twenty monomers of S25. When complexes are treated by glutaraldehyde, 10% of the genome become resistant against micrococcal nuclease. Moreover, S25 affects the DNA helical structure. Superhelical forms are generated by the association of S25 with SV40 DNA, in the presence of nicking-closing enzyme. PMID- 6255440 TI - Structure and organization of the highly repeated and interspersed 1.3 kb EcoRI Bg1II sequence family in mice. AB - EcoRI digestion of total mouse DNA yields a prominant 1.3 kb fragment amounting to between 1 and 2% of the mouse genome. The majority of the 1.3 kb EcoRI fragments have a single Bg1II site 800 bp from one end. This EcoRI-Bg1II sequence family shows HindIII and HaeIII sequence heterogeneity. We have cloned representatives of the EcoRI-Bg1II gene family in Charon 16A and studied their structure and organization within the genome. The cloned 1.3 kb fragments show the expected restriction enzyme patterns as well as additional heterogeneity. Representatives of the EcoRI-Bg1II sequence family were found to be interspersed throughout the mouse genome as judged by CsCl density gradient centrifugation experiments. Family members were also found to be organized in higher order repeating units. Homologous sequences were also found in other rodent species including rat and Chinese hamster. Cross hybridization between a cloned 1.3 kb mouse fragment and a cloned CHO repeated sequence is of special interest since the latter has been shown to contain sequences homologous to the Human A1uI family by nucleotide sequencing. PMID- 6255441 TI - Purification and properties of DNA endonucleases associated with Friend leukemia virus. AB - An endonuclease associated with the core of Friend leukemia virus (FLV) has been purified more than 10(3)-fold by ion exchange chromatography and gel filtration. Its molecular weight was determined by gel filtration to be about 40,000. Divalent cations were required for the endonuclease to function and KCl concentrations above 50 mM inhibited the enzyme activity. In the presence of Mg++ the purified enzyme nicked preferentially supercoiled circular DNA duplexes and in most of these molecules only one single-stranded nick was introduced per strand. The regions into which the nick could be introduced appeared to be randomly distributed on the circular molecule. When Mn++ was substituted for Mg++ the number of nicks introduced into DNA by the purified enzyme was greatly increased, and both relaxed circular and linear DNA duplexes were nicked as well as supercoiled circular DNA duplexes. Prior to its purification, however, in the presence of Mn++ the endonuclease activity in the virus extract was able to differentiate between circular and linear DNA duplexes, since both supercoiled and relaxed circular duplexes were nicked much more readily than linear duplexes. Single-stranded DNA functioned poorly as a substrate for the purified enzyme. PMID- 6255442 TI - Processive action of T4 endonuclease V on ultraviolet-irradiated DNA. AB - The action of the dimer-specific endonuclease V of bacteriophage T4 was studied on UV-irradiated, covalently-closed circular DNa. Form I ColE1 DNA preparations containing average dimer frequencies ranging from 2.5 to 35 pyrimidine dimers per molecule were treated with T4 endonuclease V and analysed by agarose gel electrophoresis. At all dimer frequencies examined, the production of form III DNA was linear with time and the double-strand scissions were made randomly on the ColE1 DNA genome. Since the observed fraction of form III DNA increased with increasing dimer frequency but the initial rate of loss of form I decreased with increasing dimer frequency, it was postulated that multiple single-strand scissions could be produced in a subset of the DNA population while some DNA molecules contained no scissions. When DNA containing an average of 25 dimers per circle was incubated with limiting enzyme concentrations, scissions appeared at most if not all dimmer sites in some molecules before additional strand scissions were produced in other DNA molecules. The results support a processive model for the interaction of T4 endonuclease V with UV-irradiated DNA. PMID- 6255443 TI - Structure of immunoglobulin gamma 2b heavy chain gene cloned from mouse embryo gene library. AB - A mouse DNA clone containing the constant part of the immunoglobulin gamma 2b heavy chain was isolated from a mouse gene library. The library was constructed in Charon 4A from a partial EcoRI digest of mouse embryo DNA and was screened with a plasmid (p gamma (11)7) containing a cDNA insert of the heavy chain constant region of the plasmacytoma MPC-11 (1). The Charon 4A clone contains a 14 kb insert which is cleaved by EcoRI into a 6.8 kb and 7.2 kb fragments, of which only the 6.8 kb contains the sequence for gamma 2b heavy chain. Restriction analysis and partial sequence of the insert in p gamma (11) 7 enabled us to obtain three fragments corresponding to the 5' (amino acid 161-302) middle (amino acid 302-443) and 3' (mostly non coding 107 bp) regions of the constant region. Restriction analysis of the Charon 4A clone and hybridisation to these nick translated fragments revealed that the gamma 2b constant region gene contains about 1.5 kb and has three intervening sequences. PMID- 6255444 TI - Adenovirus terminal protein protects single stranded DNA from digestion by a cellular exonuclease. AB - Adenovirus 5 DNA-protein complex is isolated from virions as a duplex DNA molecule covalently attached by the 5' termini of each strand to virion protein of unknown function. The DNA-protein complex can be digested with E. coli exonuclease III to generate molecules analogous to DNA replication intermediates in that they contain long single stranded regions ending in 5' termini bound to terminal protein. The infectivity of pronase digested Adenovirus 5 DNA is greatly diminished by exonuclease III digestion. However, the infectivity of the DNA protein complex is not significantly altered when up to at least 2400 nucleotides are removed from the 3' ends of each strand. This indicates that the terminal protein protects 5' terminated single stranded regions from digestion by a cellular exonuclease. DNA-protein complex prepared from a host range mutant with a mutation mapping in the left 4% of the genome was digested with exonuclease III, hybridized to a wild type restriction fragment comprising the left 8% of the genome, and transfected into HeLa cells. Virus with wild type phenotype was recovered at high frequency. PMID- 6255445 TI - Syntheses of some fluorescent ribonucleotides. AB - Synthesis of guanosine 3'-phosphodiesters of 1, N6-ethenoadenosine-2-sulfonate or 1, N6-etheno-2-azaadenosine can be done readily with ribonuclease N1. There is a 10-fold difference in quantum yield between the phosphodiesters and the starting fluorescent nucleosides. This difference provides the basis for the development of a fluorescent assay for nuclease. PMID- 6255446 TI - Extraction of transcribing SV40 chromosomes in very low salt. AB - SV40 chromosomes capable of continued RNA synthesis in vitro have been extracted from infected cells in solutions of very low ionic strength (5 mM HEPES, 0.25 mM MgCl2). The RNA made is of high molecular weight, and synthesis is sensitive to alpha-amanitin. More RNA is made than from previously described (high salt extracted) transcription complexes. Transcribing SV40 chromosomes sediment at a rate intermediate between replicating and mature chromosomes, and have a higher ratio of protein to nucleic acid than either. They retain proteins that are lost during exposure to high salt, and might prove valuable in identifying proteins involved in SV40 transcription. PMID- 6255448 TI - Physical and kinetic properties of the site specific endonuclease Bam HI from Bacillus amylolique-faciens. AB - The site specific endonuclease Bam HI which is composed of subunits of a molecular weight of 22 000 [1] can aggregate to complexes of a molecular weight of 360 000. It is an acidic protein with an isoelectric point at pH 5.3. Optimal activity is reached at 13 mM MgCl2. A very simple method is presented to determine kinetic constants of restriction enzymes directly from agarose gel photographs without any further equipment applying the integrated Michaelis Menten equation. With pJC 80 DNA as a substrate KM was found to be 3.6 10(-10) M. The method can be used to redefine the unit activity of site specific endonucleases unambigously. PMID- 6255450 TI - Peripheral nerve lesions--1. The start of a new three part series. PMID- 6255447 TI - In vitro splicing of SV40 late mRNA in isolated nuclei from CV-1 cells. AB - An in vitro splicing system utilizing isolated nuclei of SV40 infected cells has been developed. Nuclei were isolated from CV-1 cells at a late stage of SV40 infection after a pulse-labeling with 3H-uridine. In nuclei prepared under mild isotonic conditions, 19S viral coded RNA synthesized in vivo was converted in vitro into 16S mRNA. In contrast, the nuclei prepared with RSB, a hypotonic medium, showed a very low splicing activity only. Addition of a "nuclear extract" to these nuclei restored the activity almost to the original level. These results indicate that 1) 19S RNA is indeed a precursor to 16S mRNA 2) the splicing of 19S RNA into 16S RNA takes place in the nucleus, and 3) at least a part of the enzyme system required for splicing could be extracted from the nucleus. This in vitro system may be useful for the assay of the splicing enzyme(s). PMID- 6255449 TI - Mechanism of 3' to 5' exonuclease associated with phage T5-induced DNA polymerase: processiveness and template specificity. AB - T5-induced DNA polymerase has an associated 3' to 5' exonuclease activity. Both single-stranded and duplex DNA are hydrolyzed by this enzyme in a quasi processive manner. This is indicated by the results of polymer-challenge experiments utilizing product analysis techniques. Due to the quasi-processive mode of hydrolysis, the kinetics of label release from the 3'-terminally labeled oligonucleotide substrates, annealed to complementary homopolymers, show an initial high rate of hydrolysis. In the case of both single-stranded and duplex DNA substrates, hydrolysis seems to continue, at best, up to the point where the enzyme is five or six nucleotides away from the 5-end. The enzyme carries out mismatch repair, as evidenced by experiments with primer molecules containing improper base residues at the 3'-OH terminus. Control experiments with complementary base residues at the 3'-end indicate that extensive removal of terminal residue takes place in the presence of dNTP's only when such residues are "improper" in the Watson-Crick sense. PMID- 6255451 TI - Peripheral nerve lesions--2. The upper limb. PMID- 6255452 TI - Peripheral nerve lesions--3. The lower limb. PMID- 6255453 TI - Syndromes of ectopic hormone production in cancer. PMID- 6255454 TI - Hepatoma and obstructive jaundice. AB - Three patients with hepatoma are described whose presenting feature was obstructive jaundice. Recognition of this rare manifestation of hepatoma can establish the diagnosis before surgery. PMID- 6255455 TI - Immunological studies of transferrin and transferrin receptors of human placental trophoblast. AB - In primate pregnancy, fetal iron is derived from maternal transferrin; however, the mechanisms by which iron is taken up by the human placenta have not yet been established. In the present study, transferrin was demonstrated on the microvillous surface of human trophoblast in immunohistological studies of 130 mature and immature placentae from both normal and abnormal pregnancies. Similar results were found for baboon placentae. Upon short-term culture of placental tissue, the amount of trophoblast transferrin decreased and no incorporation of 14C lysine into transferrin could be detected by radioimmunoelectrophoresis. Thus this transferrin apparently was not synthesized by the placenta. When transferrin was removed from cryostat sections of placenta by treatment with chaotropic agents, subsequently added transferrin bound in an identical distribution. The specificity of this reaction was confirmed by the lack of binding of other serum proteins and by displacement procedures in which trophoblast transferrin was shown to be dislodged by transferrin added in vitro. These findings suggest that placental iron transport is predicated by binding of transferrin to specific receptors on trophoblast. PMID- 6255456 TI - Inhibitors of platelet aggregation in the fetoplacental unit and myometrium with particular reference to the ADP-degrading property of placenta. AB - Extracts of fresh tissue from the feto-placental unit and myometrium were tested for their ability to inhibit ADP-induced platelet aggregation and to degrade ADP. Placental extracts caused rapid reversal of aggregation and degraded ADP, both effects being mimicked by HPAP. However, whereas the latter was inhibited by L phenylalanine but not by heating to 65 degrees C for 5 minutes, the reverse was true for crude placental extracts. Umbilical cord vessels and myometrium totally inhibited platelet aggregation in a similar way to pure PGI2. Both tissues also exhibited ADP-ase activity but were much less potent in this respect than placenta. In the system used, little or no anti-aggregatory activity was detected in extracts of non-vascular cord tissue, fetal membranes or amniotic fluid, although the two latter tissues had a weak ADP-degrading effect. Thus, it appears that in contrast to myometrium and umbilical cord vessels, the major inhibitor of platelet aggregation in placenta is an ADP-ase and not PGI2. While part of the inhibitory effect of placenta may be due to HPAP, other ADP-degrading enzymes also seem to contribute to the overall anti-aggregatory property of this organ. PMID- 6255457 TI - [Effect of certain factors on the quality of the indicator tubules for determining hydrogen sulfide]. AB - Silicagel with size of granules 0.315 - 0.400 mm was used for carrier of indicator reagents in tubes for hydrogen sulphide. A planned experiment was carried out, with the purpose of establishing the influence of seven factors on the qualities of the silicagel-carrier and the tubes. It was found that essential is indicator powder porosity and humidity. An optimal amount of water to be added to keep powder humidity was found. The influence of acid processing of the carrier was also studied. Acid treatment was shown to increase carrier adsorption capacity, which affected both the ability of the carrier to take in indicator reagents and tubes quality. It was shown that tubules, prepared on the basis of acid-nontreated, but only heated at 600 degrees C carrier, are of superior quality, so long as the requirements for indicator powder humidity have strictly been observed. PMID- 6255458 TI - Modulation of cyclic AMP metabolism by S-adenosylhomocysteine and S-3 deazaadenosylhomocysteine in mouse lymphocytes. AB - Mouse lymphocytes incubated with micromolar concentrations of adenosine or 3 deazaadenosine, in medium supplemented with L-homocysteine, rapidly accumulated supramillimolar concentrations of S-adenosylhomocysteine (AdoHcy) or S-3 deazaadenosylhomocysteine (c3AdoHcy), respectively. Lymphocytes thus preloaded with high levels of AdoHcy or c3AdoHcy exhibited markedly enhanced (5- to 40 fold) cyclic AMP responses to prostaglandin E1, adenosine, 2-chloroadenosine, isoproterenol, and cholera toxin. This enhancement of cyclic AMP response by intracellular AdoHcy or c3AdoHcy was attributable both to amplification of the activity of adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] and to inhibition of cyclic AMP phosphodiesterase (3',5'-cyclic-nucleotide 5' nucleotidohydrolase, EC 3.1.4.17). Basal and prostaglandin E1- and isoproterenol stimulated activities of adenylate cyclase, assayed in lymphocyte homogenates, were increased 1.3- to 2.0-fold after treatment of the cells with homocysteine plus either adenosine or 3-deazaadenosine. AdoHcy and c3AdoHcy were found to be competitive inhibitors (with Ki values of 1.7 and 4.8 mM, respectively) of the high-affinity cyclic AMP phosphodiesterase present in lymphocyte homogenates. It is evident, therefore, that increased cellular levels of AdoHcy or c3AdoHcy can affect cellular physiology via perturbation of cyclic AMP metabolism as well as via inhibition of S-adenosylmethionine-dependent methylation reactions. PMID- 6255459 TI - Sendai virus utilizes specific sialyloligosaccharides as host cell receptor determinants. AB - Purified sialyltransferases (CMP-N-acetyl-neuraminate:D-galactosyl-glycoprotein N acetylneuraminyl-transferase, EC 2.4.99.1) in conjunction with neuraminidase (acylneuraminyl hydrolase, EC 3.2.1.18) were used to produce cell surface sialyloligosaccharides of defined sequence to investigate their role in paramyxovirus infection of host cells. Infection of Madin-Darby bovine kidney cells by Sendai virus was monitored by hemagglutination titer of the virus produced and by changes in morphological characteristics. By either criterion, treatment of the cells with Vibrio cholerae neuraminidase to remove cell surface sialic acids rendered them resistant to infection by Sendai virus. Endogenous replacement of receptors by the cell occurred slowly but supported maximal levels of infection within 6 hr. In contrast, sialylation during a 20-min incubation with CMP-sialic acid and beta-galactoside alpha 2,3-sialytransferase restored full susceptibility to infection. This enzyme elaborates the NeuAc alpha 2,3Gal beta 1,3GalNAc (NeuAc, N-acetylneuraminic acid) sequence on glycoproteins and glycolipids. No restoration of infectivity was observed when neuraminidase treated cells were sialylated by using beta-galactoside alpha 2,6 sialytransferase, which elaborates the NeuAc-alpha 2,6Gal beta 1,4GlcNAc sequence. These results suggest that sialyloligosaccharide receptor determinants of defined sequence are required for Sendai virus infection of host cells. PMID- 6255460 TI - Regulation of simian virus 40 early transcription in vitro by a purified tumor antigen. AB - Cloned DNA templates were used to direct the transcription of early and late simian virus 40 (SV40) genes by a cell-free RNA-synthesizing system. Transcription by RNA polymerase II was sensitive to low levels of alpha-amanitin and completely dependent on exogenously added DNA template. RNA products of discrete lengths were efficiently synthesized when transcription was directed by DNA restriction fragments containing promoter sequences for either early or late genes of SV40. Addition of the D2 tumor antigen to the template DNA inhibited transcription originating from the SV40 early promoter. In contrast, the D2 protein had little or no effect on the transcription from SV40 or adenovirus 2 (Ad2) late promoter sequences. When a mixture of cloned DNA containing SV40 early promoter and Ad2 late promoter was used to direct RNA synthesis, the D2 protein specifically inhibited the synthesis of SV40 early genes but not that of Ad2 late sequences. The D2 DNA binding protein also had no effect on the transcription directed by SV40 mutant templates that contain an intact early promoter sequence but lack specific tumor-antigen binding sites. We have confirmed that, under the conditions of the transcription assay, the D2 protein binds and interacts specifically with its recognition sites on wild-type template DNAs but fails to bind to mutant or Ad2 DNA templates that lack sequences containing SV40 tumor antigen binding sites. These findings provide evidence that a direct interaction between tumor antigen and its specific binding sites on DNA is the mechanism by which the SV40 A gene autoregulates its transcription. PMID- 6255461 TI - Adrenal glucocorticoid permissive regulation of muscle glycogenolysis: action on protein phosphatase(s) and its inhibitor(s). AB - Adrenal glucocorticoids exert a permissive action on the glycogen phosphorylase cascade. Epinephrine activation of muscle phosphorylase and phosphorylase b kinase is depressed in adrenalectomized rats. Phosphorylase phosphatase activity is increased by steroid lack, and normal epinephrine inhibition of the enzyme does not occur. Phosphorylase b kinase phosphatase activity is also increased; epinephrine, however, does not inhibit activity in muscle from normal or adrenalectomized rats. Protein phosphatase inhibitor activity is depressed in boiled dialyzed preparations made from adrenalectomized rat muscle. Cortisol resplacement therapy restores protein phosphatase inhibitor activity, decreases increased protein phosphatase activity, and restores normal epinephrine-induced activation of phosphorylase b kinase and phosphorylase and epinephrine inhibition of phosphorylase phosphatase. PMID- 6255462 TI - (R)-mevalonate excretion in human and rat urines. AB - (R)-Mevalonate was identified by radioenzymatic assay in human and rat urines. This was confirmed by spectrophotometric enzymatic assay of an ether extract of human urine. The average excretion rate of (R)-mevalonate in humans was 1.7 mumol/24 hr which corresponds to 29% of the glomerular filtration rate. In anesthetized rats the average rate of (R)-mevalonate excretion was 350 pmol/min, corresponding to 44% of the glomerular filtration rate. These rates were not affected by the sex of the subjects or animals. After bilateral nephrectomy, the concentration of (R)-mevalonate in rat serum increased within 2 hr to a new level that was 5 times that of sham-operated controls. Nephrectomized rats showed a decrease in their tolerance to an intravenous load of mevalonate. These data show that (R)-mevalonate is normally excreted in the urine of humans and rats. Urinary excretion of (R)-mevalonate should therefore be taken into account in in vivo studies on the metabolism of this compound. PMID- 6255464 TI - Structure of endogenous murine leukemia virus DNA in mouse genomes. AB - By using molecularly cloned ecotropic AKR murine leukemia virus (MuLV) DNA, a 400 base-pair ecotropic type-specific segment in the env region has been identified. This DNA segment and other defined viral subgenomic fragments have been used as 32P-labeled probes to identify and analyze the structure of integrated ecotropic viral DNA sequences in uninfected mouse genomes. Those mice from which endogenous ecotropic MuLV of the AKR type have been isolated contained at least one virtually complete linear copy of the viral genome. Strains from which ecotropic MuLV has not been isolated lacked ecotropic-specific sequences. All inbred mouse strains tested also contained MuLV DNAs of genomic length whose restriction endonuclease digestion pattern was characteristic of xenotropic viruses. PMID- 6255463 TI - beta-Endorphin: characteristics of binding sites in rabbit spinal cord. AB - The interaction of human beta-endorphin with binding sites in rabbit spinal cord has been characterized. The stereospecific high-affinity binding sites are concentrated in the dorsal half of the spinal cord. Scatchard analysis of the binding data shows heterogeneity of the binding sites that can be resolved into two populations with apparent dissociation constants of 3.0 (+/-2.0) X 10(-10) and 3.3 (+/- 0.5) X 10(-9) M. Sodium ions decrease the binding of human beta endorphin to spinal cord to the same extent as found in rat brain. The ability of several opiates and opioid peptides to inhibit the binding of human beta endorphin is also presented. PMID- 6255465 TI - Identification of ecotropic proviral sequences in inbred mouse strains with a cloned subgenomic DNA fragment. AB - A specific probe for detecting ecotropic murine leukemia virus sequences was constructed by cloning a 500-base-pair DNA segment, corresponding to a portion of the env region of the AKR ecotropic virus, in a pBR322/Escherichia coli K-12 host/vector system. This probe was used to screen the cellular DNAs of six inbred strains of mice for the presence of ecotropic retroviral DNA sequences by the Southern blot hybridization procedure. Three copies of ecotropic viral DNA were detected in AKR/N (a high-ecotropic virus strain) and two were found in BALB/c (a low-ecotropic virus strain) DNAs. As expected, no sequences reactive with this probe were found in NFS mouse DNA (a virus-negative strain). However, cellular DNA sequences that reacted strongly with the ecotropic-specific DNA probe were detected in certain NZB, C57L, and 129 mice (all virus-negative strains). In contrast to the reactive sequences in AKR and BALB/c, the reactions were chiefly associated with EcoRI segments that were subgenomic in size. PMID- 6255466 TI - Catabolite repression in Escherichia coli mutants lacking cyclic AMP receptor protein. AB - Pleiotropic carbohydrate-positive pseudorevertants have been isolated from a specific class of rho-crp double mutants of Escherichia coli carrying both defective transcription termination protein, rho, and cyclic AMP receptor protein. The modulation of catabolite repression of beta-galactosidase, amylomaltase, and tryptophanase has been studied in the pseudorevertants. It has been found that these mutants exhibit catabolite repression. Because catabolite sensitive operons can be expressed in the absence of functional cyclic AMP receptor protein, this would suggest on the one hand that the cyclic AMP-receptor protein complex is not the exclusive mediator of catabolite repression and on the other hand that rho might be involved in the regulation of catabolite-sensitive operons. PMID- 6255467 TI - Characterization of a receptor-like protein for 1,25-dihydroxyvitamin D3 in rat skin. AB - Isolated rat epidermis possesses a cytosolic 3.5 S receptor-like protein for 1,25 dihydroxyvitamin D3. This 3.5S binder has a high affinity (Kd = 1.4 X 10(-10) M) for 1,25-dihydroxyvitamin D3 and is present in low concentrations (31 fmol of binding sites per mg of cytosol protein). Analog competition for receptor binding revealed the following potency order: 1,25-dihydroxyvitamin D3 > 25 hydroxyvitamin D3 > 1 alpha-hydroxyvitamin D3 > 24 (R),25-dihydroxyvitamin D3 > vitamin D3. The receptor has a molecular weight of 60,000, has affinity for DNA cellulose, and aggregates in the presence of low potassium concentrations. The 1,25-dihydroxyvitamin D3 binder is stabilized by sodium molybdate (10 mM). Addition of phenylmethylsulfonyl fluoride (3 mM) was found to yield more reproducible receptor preparations. The presence of a 1,25-dihydroxyvitamin D3 binding macromolecule with properties similar to those of the bone and intestinal receptor suggests that skin is an additional target organ for this hormone. PMID- 6255468 TI - Comparison of two delta-crystallin genes in the chicken. AB - Restriction endonuclease mapping and electron microscopy established that there are at least two nonallelic delta-crystallin genes in the chicken. The structure of a complete delta-crystallin gene has been deduced by analysis of five cloned fragments from the chicken genome. Fifteen intervening sequences compose approximately 80% of this gene; the other gene contains at least 14 intervening sequences. The mRNA gene sequences appear to be similar; at least 60% divergence was found between the intervening sequences of the two delta-crystallin genes. Insertions or deletions or both appear to be major events responsible for these differences. PMID- 6255469 TI - Calcium-dependent hormonal regulation of amino acid transport and cyclic AMP accumulation in rat hepatocyte monolayer cultures. AB - The effect of glucagon, epinephrine, norepinephrine, dexamethasone, insulin, and dexamethasone plus glucagon on the transport of 2-aminoisobutyric acid (AIB) and that of glucagon on the production of cyclic AMP were examined in rat hepatocyte monolayer cultures under three different culture conditions involving calcium. The hepatocytes were studied in calcium-contaning medium after treatment with or without 0.033% dimethyl sulfoxide, the solvent for the calcium ionophore A23187 (calcium controls); calcium-free medium after treatment with A23187 (calcium depleted); and calcium-containing medium after treatment with ionophore (calcium restored). The basal and hormonally regulated rates of AIB transport for hepatocytes in calcium control and calcium-depleted cultures were comparable. The restoration of calcium in calcium-restored cultures increased the basal and the hormonally stimulated transport of AIB when compared to the other conditions. Calcium markedly enhanced the stimulation of AIB transport in cultures treated with glucagon, catecholamines, and dexamethasone plus glucagon. The level of cyclic AMP production in response to glucagon in calcium control and calcium depleted cultures was the same and it was conspicuously higher than the level in calcium-restored cultures. Varying the concentration of calcium in the medium used to maintain the hepatocytes in calcium control cultures did not affect the stimulation of AIB transport or cyclic AMP production by glucagon. However, in calcium-restored cultures, increasing the calcium concentration of the medium resulted in increased stimulation of AIB transport and decreased production of cyclic AMP by glucagon. In the calcium-restored cultures, calcium in the absence of glucagon enhanced AIB transport but had no effect on cyclic AMP production. Cultures maintained for 6 hr in calcium-free medium after the depletion of calcium showed a 6- to 7-fold increase in the production of cyclic AMP in response to glucagon, but no stimulation of AIB transport. We suggest that mobilization of cellular calcium by glucagon either directly or through cyclic AMP mediates its stimulation of amino acid transport. PMID- 6255470 TI - Effects of combined glutamine and serum deprivation on glucose control of hexose transport in mammalian fibroblast cultures. AB - Regulation of hexose transport in NIL hamster fibroblasts has been studied in confluent cultures preconditioned for 24 hr in media deprived of glutamine or of serum or of both. Cultures maintained in media containing dialyzed fetal calf serum and 4 mM glutamine accumulated up to 72 nmol of glutamine per mg of cell protein; in contrast, cells deprived of glutamine contained less than 1 nmol/mg of cell protein. Glutamine elicited a general enhancement of hexose transport compared with transport in glutamine-deprived cultures. This enhancement was particularly pronounced in glucose-fed cultures which in the absence of glutamine showed conspicuously low transport activity. When maintained in glucose media, cultures deprived of serum also showed a marked loss of hexose transport which, in this case, was not compensated for by addition of glutamine. However, regardless of the presence or absence of glutamine, these cultures were able to develop the usual transport enhancement response to glucose starvation. Moreover, 2,4-dinitrophenol was also able to elicit a pronounced enhancement of hexose transport in the glucose-fed cultures; this effect surpassed even the transport derepression observed in the glucose-starved cultures. In polyoma-transformed cultures maintained in serum-free media, hexose transport remained relatively high, even in the presence of glucose. However, addition of glutamine brought about an enhancement in both the presence and absence of serum. The various phenomena are discussed in regard to protein turnover in general and more specifically the turnover of hexose transport carriers. PMID- 6255471 TI - Platelet-derived growth factor stimulates low density lipoprotein receptor activity in cultured human fibroblasts. AB - Human platelets contain a mitogen, the platelet-derived growth factor (PDGF), that stimulates the proliferation of a variety of cell types in culture and that may play a role in atherogenesis. Studies were conducted to explore the effects of PDGF on low density lipoprotein (LDL) receptor activity of cultured human fibroblasts. The PDGF utilized in these studies was partially purified from human platelet-rich plama by ion exchange chromatography and gel filtration. LDL receptor activity was assessed by both specific binding of 125I-labeled LDL to the fibroblast's surface at 4 degrees C, and the incorporation of [14C]oleate into cholesteryl esters. Exposure of normal human fibroblasts to increasing amounts of PDGF (0.1-10 microgram/ml) for 48 hr caused a dose-related increase in 125I-labeled LDL binding to a maximum of approximately 300%. In the presence of added LDL, this increase in LDL binding was not seen. Cholesterol esterifiction was also stimulated following a 48-hr exposure to PDGF. Following a conditioning period in LDL- and PDGF-depleted medium, cholesterol esterification was greatly increased during a 48-hr exposure to LDL alone; a smaller but significant increase occurred with PDGF alone. However, both PDGF and LDL were required to return the level of esterification to that observed with whole human serum. Fibroblasts from a patient with homozygous familial hypercholesterolemia, which lack the LDL receptor, also showed a significant increase in cholesteol esterification with PDGF alone, whereas LDL had no effect. These studies demonstrate that PDGF can stimulate the LDL receptor activity in cultured human fibroblasts. The effect on other related activities of the LDL receptor system and the mechanism involved remain to be defined. PMID- 6255472 TI - Inhibiting the onset of hormone-induced desentiziation of viable thymocytes by N alpha-tosyl-L-lysine chloromethyl ketone. AB - N alpha-Toysl-L-lysine chloromethyl ketone (Tos-LysCH2Cl) was found to inhibit irreversibly the onset of the hormone-induced refractory state in intact thymocytes. When thymocytes (approximately 2 X 10(7) cells per ml) are treated with Tos-LysCH2Cl(10(-4) M, for 90 min at pH 7 and 37 degrees C) the cells retain their viability, including a full capacity to recognize and respond to hormonal stimuli, yet they selectively lose their ability to become desensitized to persistent triggering by a hormone, as reflected in the state of activation of intracellular cyclic AMP-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37). Whereas upon hormonal stimulation of untreated cells the immediate rise in the state of activation of this enzyme (up to an activity ratio of > 0.85) is followed by an exponential decline to basal values within approximately 60 min, in TosLysCH2Cl-treated cells the hormone-triggered elevation in the state of activation of the enzyme is maintained for > 60 min. Evidence is presented to suggest that in thymocytes TosLysCH2Cl inhibits the regulatory process that normally uncouples the adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] system without interfering with previous or subsequent molecular events connected with the transfer of hormonal signals across the cell membrane. This technique allows, therefore, the preparation of viable thymocytes with a limited and distinct regulatory defect introduced by chemical (covalent) means. As such, it is most useful for studies aimed at the elucidation of the mechanism of cell desensitization and for further characterization and localization of key components responsible for cellular refractoriness. PMID- 6255473 TI - Insulin and serum increase the number of receptors for vasopressin in a kidney derived line of cells grown in a defined medium. AB - A continuous strain of epithelial cells (LLC-PK1L) derived initially from pig kidney grows in a defined medium without serum or hormones. The epithelia from domes, a manifestation of transepithelial transport. The parent cell line, LLC PK1, forms similar eithelia and has vasopressin-sensitive adenylate cyclase. In this study the binding of 3H-labeled [Lys8]vasopressin was used to examine the vasopressin receptors of LLC-PK1L cells. In the absence of serum, LLC-PK1L cells have receptors with a Kd (10 nM) for 3H-labeled [Lys8]vasopressin similar to that of the parent cell line and of membranes prepared from pig renal medulla, LLC PK1L cells, however, have only 5% as many receptors as LLC-PK1 cells. The number of receptors and the vasopressin-sensitive adenylate cyclase activity are increased by growing LLC-PK1L cells in medium with 10% fetal bovine serum or with 10 microgram of insulin per ml. The combination of serum plus insulin has a greater effect than either alone. Serum and insulin do not change the apparent affinity of the receptors for vasopressin or the coupling between receptors and adenylate cyclase. Basal and NaF-stimulated adenylate cyclase activity are not affected. Several agents reported to induce receptors for hormones in other tissues have no effect on vasopressin receptors in LLC-PK1L cells. PMID- 6255474 TI - Growth of T-lymphoma cells in serum-free medium: lack of involvement of the cyclic AMP pathway in long-term cultures. AB - We have developed a serum-free, chemically defined growth medium containing casein, insulin, transferrin, testosterone, and linoleic acid in Dulbecco's modified Eagle's medium/Ham's F12 medium, 1:1 (vol/vol), for growing murine T lymphomas. This medium supports the growth in suspension of all murine T lymphomas tested, including S49, WEHI 7, EL4, BW5147, and R1.1. Growth of these cell lines was maintained indefinitely with doubling times approaching those of cells grown in 10% (vol/vol) horse serum. This medium also supports the growth of several of the S49 variants of the beta-adrenergic receptor/adenylate cyclase/cyclic AMP/protein kinase pathway, suggeting little or no involvement of this pathway in the routine growth of S49 cells or in the mechanism of action of the factors in this defined medium. This serum-free medium should prove useful for studies of a variety of metabolic pathways and of differentiated functions of T-lymphoma cells. PMID- 6255477 TI - Frequency and levels of antibodies to Epstein-Barr virus-specific DNase are elevated in patients with nasopharyngeal carcinoma. AB - Sera from healthy individuals and patients with infectious mononucleosis, Burkitt lymphoma, nasopharyngeal carcinoma, or other malignancies were examined for their capacity to neutralize Epstein-Barr virus (EBV)-induced DNase activity. Sera were found that neutralized the EBV DNase but not herpes simplex virus type 1 or type 2 DNases, and vice versa. Sera from 46 of the 49 patients with nasopharyngeal carcinoma examined (94%) neutralized > 6 units of EBV DNase per ml of serum. In contrast, only 19% of 47 patients with Burkitt lymphoma, 12% of 183 patient with other malignancies, 4% of 58 patients with infectious mononucleosis, and none of 101 healthy individuals had such levels of neutralizing activity. The neutralizing factor was found in the IgG fraction derived from nasopharyngeal carcinoma sera. There was no correlation between the concentration of these antibodie and the titers of IgG ad IgA antibodies to the EBV capsid antigen, the early antigen complex, or the EBV-associated nuclear antigen. PMID- 6255478 TI - Cytotypically specific transfecting activity of DNA from C57BL/Ka mouse cells producing thymotropic in contrast to nonthymotropic retroviruses. AB - A comparative study has been made of the susceptibility of fibroblastic cells to transfection by DNA from C57BL/Ka mouse lines producing either fibrotropic or thymotropic retroviruses. DNA isolated from fibroblasts that release a B ecotropic, fibrotropic virus, BL/Ka(B), was found to transfect fibroblasts of Fv 1bb genotype with release of virus similar to BL/Ka(B). Fv-1nn fibroblasts were also susceptible but expression was delayed, and xenotypic mink lung cells were refractory. In contrast, DNA prepared from a murine T-cell lymphoma line producing a B-ecotropic, thymotropic virus failed to transfect mouse fibroblasts though it transfected a nonproducer T-cell lymphoma line. The data suggest that the Fv-1 and differentiation-specific restriction mechanisms operate at different molecular levels. PMID- 6255476 TI - Antigen-liposome modification of target cells as a method to alter their susceptibility to lysis by cytotoxic T lymphocytes. AB - A method of liposome modification of cell surfaces to render unsuitable target cells susceptible to lysis by anti-viral cytotoxic T lymphocytes (CTLs) is described. Liposomes containing the hemagglutinin-neuraminidase (HN) and fusion (F) glycoproteins of Sendai virus as well as purified H-2Kk cells and rendering those cells susceptible to lysis by B10. A anti-Sendai virus or anti-H-2Kk CTLs. The absence from the modifying liposomes of the HN or F proteins or H-2Kk antigens eliminated the ability of the target cells to be recognized and lysed by either effector cell population. Vesicles containing HN, H-2Kk molecules, and inactive fusion protein (Fo) were not capable of increasing the susceptibility of h-2-negative target cells to lysis. Liposomes containing inactive fusion protein were similarly unable to render H-2-positive target cells susceptible to lysis by anti-Sendai virus CTLs, suggesting that fusion of the liposomes to the cell surface is a prerequisite to lysis. It did not appear that attachement of liposomes to the cell surface was sufficient for generation of susceptible targets, however, because attachment to the cell surface was observed, as long as the HN glycoprotein was present in the liposomes. These results indicate that purified H-2Kk glycoproteins are target antigens for anti-H-2k CTLs and that B10 . A anti-Sendai virus CTLs recognize in an H-2-restricted manner the HN, F, or both glycoproteins of Sendai virus in the context of the purified H-2Kk glycoproteins. This technique of liposome modification of cell surfaces has potential applications in the examination of CTL antigen recognition and immunotherapy of many viral and neoplastic diseases. PMID- 6255475 TI - Regulation of Tn5 transposition in Salmonella typhimurium. AB - The drug-resistance element Tn5 transposes with high frequency immediately after entry into a cell. Establishment of Tn5 within a cell results in a decrease in this transposition frequency. This phenomenon resembles "zygotic induction" of repressible operons and prophages. Evidence is presented that Tn5 transposition is under negative control by a factor encoded within the element itself. Established Tn5 elements (that contain point mutations inactivating the resistance gene) are able to inhibit transposition of an incoming Tn5 element by a factor of 12- to 70-fold. Several deletion derivatives of Tn5 lack the ability to inhibit transposition. PMID- 6255479 TI - An endonuclease isolated from Epstein-Barr virus-producing human lymphoblastoid cells. AB - An endonuclease has been isolated from human B lymphoblastoid cells that copurifies with an exonucleolytic activity and has been shown to produce double strand breaks and a high proportion of single-strandedness in phage lambda DNA in vitro. The data are consistent with a model in which single-strand cuts are made by the endonucleolytic activity, possibly in A+T-rich regions of the DNA, followed by creation of single-stranded regions (gaps) precessing from the site of a cut. Generation of overlapping gaps on opposite strands or of a gap opposite a nick would lead to the creation of the banding patterns that we have seen on electrophoretic gels. This endonucleolytic activity copurifies with other enzymes induced by Epstein-Barr virus that relate to the process of viral DNA replication in productively infected cells. However, a more general role is proposed for this class of eukaryotic endonuclease activities. A marked degree of single strandedness has been found in the replicating DNAs of many eukaryotes, ad these gaps could be generated by endonucleases with associated exonucleolytic activity such as that reported here. This Epstein-Barr virus-induced nuclease activity has been shown to resemble the recBC nuclease isolated from the prokaryote Escherichia coli and also the endonuclease isolated from the eukaryote Chlamydomonas. PMID- 6255480 TI - Characterization of Y73, an avian sarcoma virus: a unique transforming gene and its product, a phosphopolyprotein with protein kinase activity. AB - The Y73 strain of avian sarcoma virus recently isolated in Japan is defective in replication and is associated with subgroup A leukosis virus (YAV). The virus caused sarcoma but not acute leukosis when inoculated into chickens. Studies on the viral RNA showed that a 26S RNA, etimated to be 4.8 kilobases long, was Y73 viral RNA carrying a transforming gene. The 26S RNA has sequences in common with the RNA of an avian leukosis virus but no homology with the src gene sequence of avian sarcoma virus (ASV). Thus, Y73 has a unique sarcoma-inducing gene. A phosphorylated polyprotein of 90,000 daltons (p90) was immunoprecipitated from extracts of Y73-transformed chicken embryo cells by a variety of antisera reacting with gag gene products. When a bacteria-bound immunocomplex containing the p90 protein was incubated with [gamma-32P]ATP, the Y73-specific p90 and the IgG heavy chain were phosphorylated by a p90-associated protein kinase. The amino acid phosphorylated in vitro was exclusively tyrosine in both cases, whereas p90 phosphorylated in vivo contained phosphoserine as a major phospho amino acid with traces of phosphotyrosine and phosphothreoine. PMID- 6255481 TI - Avermectin B1a, a paralyzing anthelmintic that affects interneurons and inhibitory motoneurons in Ascaris. AB - Avermectin B1a (AVM) is an antiparasitic agent that paralyzes nematodes without causing hypercontraction or flaccid paralysis. Using selective stimulation techniques, we have shown that AVM blocks transmission between interneuron(s) and excitatory motorneurons in the ventral nerve cord of Ascaris. It also inhibits transmissin between inhibitory motoneurons and muscle but has little effect on excitatory neuromuscular transmission. Picrotoxin can reverse the AVM-induced block of interneuron-excitatory motoneuron transmission but has no effect on the inhibitory motoneuronal synapse in either the presence or absence of AVM. Our results provide an explanation of how AVM may cause paralysis of nematodes. PMID- 6255482 TI - Facilitation of membrane electrical excitability in Drosophila. AB - Prior electrical activity in the indirect flight muscles of Drosophila facilitates membrane excitability. The mechanism of facilitation involves the inactivation of an early, fast, transient outward current by prior membrane depolarizaton. In the facilitated state the calcium-dependent spike-like response has a decreased current and voltage threshold. The facilitated state persists for 1.5 sec after a membrane active response. A single nerve-driven spike is sufficient to facilitate membrane excitability. PMID- 6255483 TI - Differentiation of delta and mu opiate receptor localizations by light microscopic autoradiography. AB - We have observed two discrete populations of opiate receptors that are differently localized in rat brain. Morphine-like (mu) receptors, labeled by 125I labeled [D-Ala-2MePhe4Met(O)5-ol]enkephalin, are concentrated selectively in lamina IV of the cerebral cortex, certain thalamic nuclei, and the periaqueductal grey, while delta receptors, labeled by 125I-labeled [D-Ala2-D-Leu5]enkephalin, are more diffused, having high densities in cerebral cortex, corpus striatum, amygdala, and olfactory tubercle. Because of similarities in their localizations, we propose that mu and delta receptors are respectively the physiologic receptors for [Met]- and [Leu]enkephalin neurons. These distributions reflect the different physiological functions attributed to mu and delta receptors and thus represent discrete functions of [Met]- and [Leu]enkephalin neurons. PMID- 6255484 TI - Electrical inhibition of Purkinje cells in the cerebellum of the rat. AB - Monosynaptic activation of cerebellar Purkinje cells by a volley of parallel fiber impulses is followed by a powerful disynaptic chemical inhibition mediated by molecular layer interneurons, including basket cells. Active zone established by basket preterminal axons on the body surface of the Purkinje cell account for this inhibition. However, morphological studies indicate that branches of the presynaptic fibers further descend along the initial segment of the Purkinje axon. Terminals from several basket cells converge and encapsulate each initial segment with a peculiar architectural structure that is reminiscent of that characterizing the axon cap of the teleost Mauthner cell. Because no function has yet been attributed to this pinceau, we have reanalyzed the successive Purkinje cell responses to activation of their presynaptic elements. Electrophysiological data provided by field-potential and single-unit measurements indicate that the classical phases of excitation and inhibition after a parallel-fiber volley are preceded by a brief inhibition of the Purkinje cells. Transmembrane hyperpolarizing potentials that exhibit the characteristics expected of electrically mediatd potentials underlie this early phase of inhibition; their properties are consistent with the hypothesis that they are generated by currents through terminals of nearby basket cells. Therefore, these hyperpolarizations, which are similar in their mechanism of generation to those described in the Mauthner cell system, represent a known case of electrical inhibition in the mammalian central nervous system. PMID- 6255485 TI - Changes in hormone action during aging: glucocorticoid regulation of adipocyte glucose metabolism and catecholamine regulation of myocardial contractility. PMID- 6255486 TI - Morphine-like peptides: their regulation in the neuroendocrine system and the effect of guanyl nucleotides and divalent ions on opiate receptor binding. AB - Glucocorticoids such as dexamethasone and prednisolone at physiological concentrations inhibit the synthesis, and hence the release, of endorphins by AtT/20 pituitary cells. Several other steroids, including progesterone, estradiol benzoate and testosterone, have no such effect and do not compete with dexamethasone. Incorporation of 3H-dexamethasone into nuclei of AtT/20 cells was inhibited by a much lower concentration of dexamethasone or prednisolone than that of several other steroids studied. This study indicates for the first time that glucocorticoids directly inhibit synthesis of endorphins by pituitary cells. The effect of GTP and GMP-PNP on the binding of 3H-D-ala-methionine enkephalin to rat brain opiate receptors was studied. Different brain regions showed different sensitivity to GMP-PNP. Manganese, calcium and magnesium selectively inhibited the effect of GMP-PNP but barium and strontium had no effect. The possibility that divalent cations alter the coupling of opiate receptors to internal components is suggested. PMID- 6255487 TI - Opioid peptides and their receptors. AB - The three agonists, methionine-enkephalin, leucine-enkephalin and beta-endorphin have different pharmacological patterns. It may be of particular importance that they vary in their relative affinities to the enkephalin and naltrexone binding sites in the brain; the former are probably related to delta-receptors prevalent in the mouse vas deferens and the later to mu-receptors prevalent in the guinea pig. It is possible that mu-receptors are more important for the mediation of analgesic effects than delta-receptors. An understanding of the pharmacokinetics of the opioid peptides will be of basic importance for the design of enkephalin analogues suitable for use as analgesics in man. PMID- 6255488 TI - Characterization of humoral endorphin. AB - Utilizing a radioimmunoassay (RIA) with antibodies produced against leu enkephalin, the presence of humoral endorphin in various body fluids and tissues has been shown. Pretreatment with trichloroacetic acid (TCA) was needed in all cases in order to detect the immunoreactivity. However, both treated and untreated samples of humoral endorphin were active in the opiate receptor assay. Gel filtration on Bio-Gel P-2 as well as on Sephadex G-10 columns of human cerebrospinal fluid (CSF), amniotic fluid (AF) and blood shows that they all contain a similar material with an apparent molecular weight of 1,000-1,400 daltons. Chromatography of rat brain homogenate exhibited two peaks of immunoreactivity, one of which is probably due to enkephalins and the other to humoral endorphin. The latter fraction was found to be very stable when incubated in CSF, while its degradation in blood was slightly faster. This opioid compound inhibited the electrically stimulated contractions of the guinea pig ileum; the specificity of this action was indicated by its reversal with low concentrations of naloxone. In pregnant women, humoral endorphin levels in maternal and cord blood remains stable during pregnancy, while there is a significantly higher concentration of humoral endorphin in the amniotic fluid at mid-trimester as compared to that in term pregnancies during labor. PMID- 6255489 TI - Humoral endorphin: can in vitro experiments explain in vivo results? AB - Humoral endorphin, an endogenous substance isolated from brain, blood and cerebrospinal fluid, reveals non-conventional interactions with both opiate agonist (morphine) and antagonist (naloxone) in the guinea pig ileum bioassay. The opioid activity of humoral endorphin is potentiated by pretreatment of the preparation with morphine and vice versa. Naloxone, a specific opiate antagonist, interacts with humoral endorphin in a distinct manner which distinguishes it from opiates: while low concentrations of naloxone antagonize the effect of humoral endorphin, high concentrations of the antagonist are less effective and even potentiate its opiate activity. These interactions between opiate agents can be explained assuming conformational transformation of the opiate receptor. The in vitro interactions shed new light on paradoxical and conflicting results of in vivo experiments and indicate the physiological function of humoral endorphin. PMID- 6255490 TI - Biosynthesis of neuronal peptides: implications for neurobiology. AB - Many biologically active peptides (e.g., insulin, nerve growth factor, ACTH, endorphin, parathyroid hormone, etc.) appear to be synthesized first as prohormones, which are then converted intracellularly to the biologically active products by various post-translational modifications. Peptides of neuronal origin (e.g., vasopressin and oxytocin) are synthesized by similar mechanisms. The prominent role of post-translational processing in determining the final peptide products allows for the possibility that different peptides will by generated from identical prohormones in different cells. PMID- 6255491 TI - The effect of acute ethanol administration on the activity of membrane-bound enzymes of rat liver. PMID- 6255492 TI - The influence of thyroid function on ouabain accumulation by the rat heart. PMID- 6255493 TI - Cathinone, active principle of the khat leaf: its effects on in vivo and in vitro lipolysis. PMID- 6255494 TI - Development of drug resistance and dependence in viruses. PMID- 6255495 TI - The responses of the developing endocrine system to hormones and drugs. PMID- 6255496 TI - Clostridium perfringens toxins (type A, B, C, D, E). PMID- 6255497 TI - Structure-CNS activity studies with the enkephalins. PMID- 6255498 TI - Glucose analogues in the chemotherapy of herpesvirus infections. PMID- 6255499 TI - LPH, ACTH, MSH and motor systems. PMID- 6255500 TI - Positive reinforcement produced by noradrenergic stimulation of the hypothalamus in rats. PMID- 6255501 TI - Inhibitory and facilitatory neural mechanisms involved in the regulation of lordosis behavior in female rats: effects of dual cuts in the preoptic area and hypothalamus. PMID- 6255502 TI - Preliminary observations with a technique for measuring current spread in the rat brain. PMID- 6255503 TI - [Patterns of psychiatric follow-up care outside the psychiatric hospital (author's transl)]. AB - This study was devoted to collecting information from 57 psychiatric hospitals in the Federal Republic of Germany with regard to the quality of the care afforded to chronic psychiatric patients. The study took place during 1977/1978, and concerned the therapeutic and general quality of transitional hostels, homes for long-term follow-up care, and homes for the aged and multiple-handicapped patients. At the same time, the present-day effectivity of sociolegal rehabilitation aid measures was compared with the results of corresponding opinions polls conducted in 1973/1974. The following conclusions were drawn: 1. "Non-clinical" mental health care of chronic psychiatric patients (mentally handicapped persons) requires specific pedagogico-therapeutic programmes specially adapted to the requirements of these patients. These requirements differ considerably from the conventional style of "ward care" which has developed in psychiatric hospitals. Regional fusion or co-operation of these homes is strongly recommended. 2. The effectivity of sociolegal rehabilitation aids for the mentally handicapped continues to be very low. This is partly due to the poor level of training and knowledge of the therapeutic personnel. Hence it is absolutely imperative to arrange for knowledge of this admittedly rather dry sociolegal subject matter, by means of suitable training and instruction. PMID- 6255504 TI - [Hostels for the mentally (psychically) handicapped (author's transl)]. PMID- 6255505 TI - [Caring for psychiatric patients in proximity to their domicile or, more than one approach may be feasible (author's transl)]. AB - The arguments in favour of caring for psychiatric patients in locations which are close to their domicile, are by no means new. Practically all of these arguments had already been brought forward by Griesinger, and we can also read them up in the minutes of the meetings of the Federal Germany Parliamentary Committee for Youth, Family and Health Problems. A frequent argument against the decentralisation of psychiatric care by setting up psychiatric departments in general hospitals is that this would eventually lead to a kind of two-class psychiatry. In simplified language, this would imply that those patients who are acutely diseased, are admitted to a general hospital, whereas the chronically diseased persons remain in the large-scale psychiatric Land hospital. However, this is not necessarily so, if such psychiatric departments of regional competence are compulsorily allocated to a certain area, which means they are compelled to admit patients residing in their area, while being prohibited from transferring these patients to another, far-away hospital. The departments in Rheydt and Hanover, for example, show that relevant experience collected outside Germany applies likewise to the Federal Republic. In fact, the reports published by these two hospitals show that psychiatry conducted close to the domicile of the patients improves outpatient follow-up of patients with chronic disturbances, whereas the number of compulsory admissions is dramatically reduced. On the other hand, the rate of admission is increased, and the period of hospitalisation reduced. In the long run, this results in a pattern of psychiatric care in which long-term outpatient therapy predominates. We can sum up by saving that community centered and population oriented working is by no means a panacea for all problems of psychiatric care which have remained unsolved to data. However, experience has shown that the method is feasible and, on the whole a promising one. It is precisely the return of psychiatry to the communal level which opens up non-professional resources which would otherwise remain untapped. It must be borne in mind, however, that the physician's own psychiatric practice is exposed to the public eye to greater extent than before. This offers a real chance. The psychiatrist can take advantage of this chance only if he develops a kind of sixth sense for social processes and requirements within the community, for the best way to influence them, and to make use of them for translating one's own goals into reality. Of course, this will always involve the risk of overstepping one's own area of jurisdiction, but this need not be dramatised. PMID- 6255506 TI - Erythrocyte membrane cation carrier in manic-depressive psychosis. AB - Erythrocyte Na-K ATPase and sodium pump site numbers were estimated in groups of depressed, manic and recovered patients. The activity of Na-K ATPase per pump site was lower in the depressed group than in the recovered group. In the manic group Na-K ATPase was lower than that of the recovered group, whereas there was no difference in the pump site numbers. In the more severe manics the activity of Na-K ATPase per pump site was significantly lower than that of the recovered patients. Therefore, the change occurring in the erythrocyte membrane cation carrier in manic-depressive psychosis is probably in the activity of individual Na-K ATPase molecules and not in the number of Na-K ATPase molecules per cell. PMID- 6255507 TI - The possible relationship of herpes simplex virus infection to cause of retardation in severe mental handicap. AB - The relationship between herpes simplex virus type 1 and mental retardation is explored by studying the antibody levels to this virus in a group of 86 severely and profoundly retarded adults. A tendency towards higher antibody levels is found in patients whose retardation is of unknown aetiology. The relationship of these observations to previous research findings and the possible significance of herpes simplex virus in the aetiology of mental retardation are discussed. PMID- 6255508 TI - An abstinence syndrome following chronic administration of delta-9 terahydrocannabinol in rhesus monkeys. AB - Chaired, chronically catheterized rhesus monkeys were administered IV delta-9 tetrahydrocannabinol (THC), 0.5 mg/kg every 6 h for 3 weeks. Following the first THC injection, the animals appeared heavy-lidded, immobile, and unresponsive to observation. Tolerance developed to these behaviors during the 3 weeks of THC administration, although the animals remained subdued compared to baseline. Following discontinuation of THC, animals showed an increase in gross movement, eye contact, and tooth baring of greater frequency and/or duration than observed before THC. This presumably represents a cannabis abstinence syndrome. PMID- 6255509 TI - [Toxicity and radioprotective effect of certain sulfur-containing protectors when administered orally in combination]. PMID- 6255510 TI - [Pathology and natural history of mass-lesion in the spinal cord, its covers and in the neighbouring vertebral column (author's transl)]. AB - Space-occupying lesions occurring in the spinal cord, its covers and in the neighbouring vertebral column are reviewed with consideration to their favourite site and the patients age and sex. The main tumor types are described with special reference to the literature and a comparison is made to the findings of specific tumors when occurring intracranially. PMID- 6255511 TI - Computed tomography of pineal, parapineal, and histologically related tumors. AB - Thirty-one of 32 pineal and related tumors were diagnosed by computed tomography (CT). There were 7 germinomas, 4 primary pineal tumors, 4 embryonal cell carcinomas, one teratoma, one epidermoid, one primitive neuroectodermal tumor, 8 astrocytomas and 6 lipomas. Histologic confirmation was obtained in 22. The CT characteristics allow differentiation of benign tumors such as teratomas and epidermoids from malignant germinal lesions such as germinoma and embryonal cell carcinoma. Abnormal calcification occurs most frequently in the primary pineal tumors, pineoblastoma and pineocytoma. The CT characteristics and consideration of the patient's age and sex often lead to histologic prediction and better treatment planning. PMID- 6255512 TI - Further observations on the medical efficacy of computed tomography of the chest and abdomen. AB - A review of 262 consecutive 2-second CT scans (101 thoracic and 161 abdominal) revealed that 36% contributed information critical to diagnosis, prognosis or therapy. As a result of CT-derived data, major surgery was cancelled in 16 cases and planned surgery modified in 11. Similarly, CT contributed to treatment planning in 20 instances. Forty-four per cent of the studies produced new information but did not have definite clinical impact. Marked improvement in efficacy is noted when these data are compared to our previous study of 2 1/2 minute CT examinations. The improvement is ascribed to better imaging (faster scan speed), improved diagnostic skill, better patient selection, and improved credibility of CT-derived data. PMID- 6255513 TI - Carcinoma of the urachus: the role of computed tomography. AB - Carcinoma of the urachus is a rare entity with poor prognosis. Calcification, a deformed bladder apex, and lateral ureteral displacement have been described as radiographic findings, although radiology has been considered to be of limited value in establishing the diagnosis. Two cases are reported in which computed tomography (CT) contributed to the diagnosis and management. The association of a calcified suprapubic mass on CT together with a history of the passage of blood and mucus per urethra is suggestive of the diagnosis. PMID- 6255514 TI - Intraoperative ultrasound examination of the brain. AB - In a preliminary demonstration of cranial intraoperative real-time ultrasound, both supratentorial and posterior fossa scans displayed the pertinent anatomy. A grade III astrocytoma was visualized on the supratentorial scan as well. Ultrasound may be valuable for surgical planning and biopsy procedures because of its reliable depiction of intracranial anatomy and ease of use. PMID- 6255515 TI - Familial polyposis coli. PMID- 6255516 TI - [Unusual career of plant fiber in human pathology (author's transl)]. PMID- 6255517 TI - [Gastric carcinoma: morphological patterns of prognostic value]. PMID- 6255518 TI - High-dose methotrexate in combination chemotherapy for small cell lung cancer. AB - High-dose methotrexate and Leucovorin (calcium folinate) rescue was evaluated as induction chemotherapy in combination with cyclophosphamide, doxorubicin, and vincristine in 21 patients with extensive-stage small cell lung cancer. Nine (42%) of 21 had a complete remission. The median duration of remission has been short (5 months), and attempts are now under way to improve consolidation chemotherapy. In general, the degree of myelotoxicity was not increased by the high-dose methotrexate, although the antitumor activity of the combination appears enhanced. Attempts at further increasing the intensity of this regimen or comparative trials with other therapy appears warranted. PMID- 6255519 TI - Adjuvant therapies of postsurgical minimal residual disease. AB - The review summarizes the most recent results obtained with present combined adjuvant strategy for the treatment of resectable cancer. Recent important randomized clinical trials, either unicentric or polycentric, are discussed. As far as pediatric tumors are concerned post-surgical adjuvant chemotherapy was proved to play a useful role in prolonging the disease-free survival in Wilms tumor, rhabdomyosarcoma, Ewing sarcoma. Results obtained in the treatment of medulloblastoma and osteogenic sarcoma need further investigations. In adult neoplasms the most important results with combined modality approach are presently being obtained in breast cancer and probably in melanoma. No consistent improvement by adjuvant chemotherapy has been observed in colorectal cancer. PMID- 6255521 TI - Serum copper levels in patients with lung cancer. AB - An increased mean serum copper level was found in 149 patients with lung cancer when compared with 19 healthy people and 23 patients with non-malignant lung diseases. The level seemed to reflect the stage of disease, with asymptomatic patients showing the lowest values, and patients with metastatic symptoms the highest. In spite of significant differences between the groups of subjects the scatter in the values was large. Hence serum copper determinations can be of only limited importance for differential diagnosis or in assessing the clinical stage of cancer. No differences in copper levels were found between the groups of patients with different histological types of lung cancer. PMID- 6255520 TI - Comparison of the alpha-adrenergic agonists, phenylephrine and methoxamine in rabbit papillary muscles. AB - The positive inotropic effects of the alpha-adrenergic agonists, phenylephrine and methoxamine were compared in isolated rabbit papillary muscles. Phenylephrine in the presence of 10(-7)M propranolol produced a greater response than methoxamine. Antagonism by phentolamine was competitive for phenylephrine and apparently, noncompetitive for methoxamine. Based upon observed maximum following frequencies, 10(-4)M methoxamine had a greater cardiac depressant effect than 10( 4) phenylephrine. It was suggested that phenylephrine with a beta-adrenergic antagonist possessed advantages over methoxamine as an agonist for studying cardiac alpha-adrenergic receptors in rabbit papillary muscles. PMID- 6255522 TI - Epithelial lesions suggestive of a condylomatous origin found closely associated with invasive bronchial squamous cell carcinomas. AB - The histology of the bronchial specimens derived from 104 patients with an established invasive bronchial squamous cell carcinoma was assessed with special reference to the detection of the morphological manifestations of human papilloma virus (HPV) recently described in the uterine cervix, i.e., three different types of condylomatous lesions (papillomatous, flat and endophytic). Histological lesions fulfilling the criteria of papillomatous condyloma were found in 6 cases, those of endophytic condyloma in 4 cases, and lesions identical to flat type condyloma of the uterine cervix were encountered in 26 cases (25%). The role of HPV in the development of these lesions and their relationship to squamous cell carcinogenesis was discussed, and a concept hypothesizing the development of bronchial squamous cell carcinoma is outlined. PMID- 6255524 TI - RNA viruses, cancer and development. PMID- 6255525 TI - Hepatocarcinogenesis as a problem in developmental biology. PMID- 6255523 TI - The effects of temperature-sensitive Rous sarcoma virus and phorbol diester tumor promoters on cell lineages. PMID- 6255527 TI - Tracheal volume in the pupa of the Saturniid moth Hyalophora cecropia determined with inert gases. AB - Tracheal volume (VTr) was measured in pupae of the Giant silkworm moth Hyalophora cecropia (Saturniidae, Lepidoptera, Insecta) using inert gas wash-out techniques. The animal was placed in a small vessel that was continuously ventilated (rate, V) by a gas mixture containing 20% O2 in N2; the inflowing (F1) and outflowing gas fractions (FE) of the vessel could be continuously measured by a respiratory mass spectrometer. At the onset of a spiracular constriction period, which was evidenced from the FECO2 trace, the mixture was rapidly replaced by pure Ar. At the subsequent burst, the amount of N2 emerging from the animal, MN2, was calculated from V and the difference (FE--F1)N2. VTr was calculated from MN2 and the N2 concentration in the tracheal system before constriction (assumed to equal that in the ventilating gas before replacement by Ar). Measurements were repeated with N2 and Ar replacing each other. VTr average 48 microliter . g-1 (range 39 to 59) for animals of 5.8 g average body weight (range 3.4 to 9.9), when inert gas solubility in body fluids was accounted for. Both size and stage in pupal development appear to affect VTr. These values show reasonable agreement with literature data, mostly obtained by emptying the tracheal gas space by mechanical compression. PMID- 6255526 TI - Development of embryo-derived teratomas in vitro. PMID- 6255528 TI - [Familial, malignant, chemodectoma bilateral in a 16-year-old girl]. PMID- 6255529 TI - First International symposium on ketoconazole. Medellin, Colombia, November 29 and 30, 1979. PMID- 6255530 TI - Ketoconazole in early and late murine coccidioidomycosis. AB - Ketoconazole (35 mg/kg) was administered orally to mice twice daily, beginning at different intervals after intranasal infection with arthrospores of Coccidioides immitis. When treatment was begun on the fourth day after infection, before extensive extrapulmonary dissemination of the infection had occurred, all animals survived, and extension of the disease from lungs to liver, spleen, and kidneys was prevented. Mortality was 90% in untreated control animals. In most of the drug-treated animals, lung lesions were not rendered free of fungus after 21 days of treatment. When treatment was begun on the 12th day of infection, after extrapulmonary dissemination had occurred, the drug was life-preserving. However, lesions of the peritoneal organs of 30%--60% of the surviving animals and pulmonary lesions of 90% of these animals harbored viable fungi after 82 days of treatment. Mortality was lower when treatment was given from the 35th through the 120th day after infection to survivors of a challenge dose that was lethal to 28% of the animals within 30 days. These data indicate that the antifungal activity of the drug observed in vitro also operates in vivo. Mycologic cure was optimal when infections were treated early. It became difficult to eradicate the fungus once it became entrenched in lesions of the peritoneal organs or lungs. PMID- 6255531 TI - Combination therapy of experimental histoplasmosis and cryptococcosis with amphotericin B and ketoconazole. AB - Combinations of amphotericin B and ketoconazole had an additive effect in vitro against Histoplasma capsulatum and Cryptococcus neoformans; ketoconazole combined with flucytosine exerted an indifferent effect against C. neoformans. In vivo studies in athymic nude (nu/nu) mice and their heterozygous (nu/+) littermates demonstrated that treatment with the ketoconazole-amphotericin B combination resulted in longer survival of mice with cryptococcosis than did treatment with ketoconazole plus flucytosine. However, mice given ketoconazole plus amphotericin B did not survive significantly longer than those given amphotericin B alone (cryptococcosis) or ketoconazole alone (histoplasmosis). Combination chemotherapy with ketoconazole and amphotericin B may offer a modest therapeutic advantage over therapy with either drug alone. PMID- 6255532 TI - Ketoconazole in experimental candidosis. AB - A relatively large number of animal models of candidosis exist in which the efficacy of antifungal substances can be evaluated. These include models of candidosis of the skin, gastrointestinal tract, genital system, and internal organs in a variety of animal species. The efficacy of ketoconazole administered orally and topically was evaluated; when given orally in relatively low doses, ketoconazole was found to be efficacious in all of the experimental models used. Scanning and transmission electron micrographs of infected tissue demonstrated the rapidity with which Candida albicans was eradicated from the host after administration of ketoconazole. PMID- 6255533 TI - Oral therapy with ketoconazole for dermatophyte infections unresponsive to griseofulvin. AB - Oral ketoconazole therapy was evaluated with 21 patients who had recalcitrant dermatophytosis. During an 18-week period, all patients, including three with organisms resistant to griseofulvin in vitro, showed impressive clinical improvement. The four patients without nail involvement became mycologically negative earlier than those with onychomycosis. The latter group showed progressive clearing of the nails, but only three were mycologically clear after 18 weeks. Adverse reactions to ketoconazole were negligible, and no patients required discontinuance of the drug. Ketoconazole appears to be a safe, effective drug for oral therapy of dermatophytoses in humans. PMID- 6255534 TI - Treatment of dermatomycoses with ketoconazole. AB - Forty patients (22 males and 18 nonpregnant females) with tegumentary mycoses were treated with ketoconazole (R41,400). The group included 39 patients with dermatophytoses and one with tinea versicolor. Ketoconazole was administered in one dose per day taken with water 2 hr before or after breakfast for one month; patients weighing < 30 kg received 100 mg of ketoconazole per day, whereas those weighing > 30 kg received 200 mg per day. Twenty-one patients had complete clinical and mycologic cure, two responded clinically but the last culture was positive, eight had partial improvement, and three had no improvement at all. In six cases the treatment was stopped (in one because of gastric intolerance). The main adverse effect of ketoconazole was nausea; only one patient had vomiting. The results indicate that ketoconazole is a safe and effective drug for treatment of dermatomycosis. PMID- 6255535 TI - A multi-center, double-blind comparison of ketoconazole and griseofulvin in the treatment of infections due to dermatophytes. AB - The efficacy and safety of daily doses of 200 mg of ketoconazole or 250 mg of griseofulvin (Fulvicin-P/G, Schering, Kenilworth, N.J.) in the treatment of patients with infections due to dermatophytes are being evaluated in a three center study. Patients with chronic dermatomycoses resistant to topical treatment or with infections that involve large areas of the body, a condition that indicates oral therapy, are being treated for a minimum of four weeks. Eleven (38%) of 29 patients treated with ketoconazole for four weeks and five (24%) of 21 patients treated with grisofulvin for the same amount of time were rated as cured. At completion of therapy (four to eight weeks), 24 (83%) of 29 patients treated with ketoconazole and six (32%) of 19 patients treated with griseofulvin were rated as cured (P = < 0.001). One (7%) of 14 patients treated with ketoconazole and four (80%) of five patients treated with griseofulvin were rated as relapsed within 28 days after completion of therapy (P = 0.006). No significant adverse effects have been reported for either treatment group. The preliminary results of this study have shown ketoconazole to be more effective than griseofulvin in the treatment of dermatomycoses. PMID- 6255536 TI - Treatment of pityriasis versicolor with ketoconazole. AB - Eighty-two patients with pityriasis versicolor were treated orally with ketoconazole in tablet form (200 mg). The tablets were taken at least 90 min before a meal, and patients who received only one tablet daily were told to refrain from bathing except immediately before ingestion of the drug and only once a day. Dosage of ketoconazole varied from a single dose of 400 mg to 200- 400 mg per day for four weeks. Seventy-seven patients reported no adverse effects. There were reports from others of headache, gastralgia, nausea, dyspnea, dizziness, or tinnitus. In most affected patients, these symptoms stopped with the first meal eaten after initiation of treatment. Follow-up examinations were performed at different intervals. The maximal therapeutic effect of ketoconazole was seen three to six weeks after initiation of therapy. Seventy-eight patients were considered cured; one had received only one tablet. Only hypopigmented macules remained. Examination of these areas with a Wood lamp revealed no fluorescence, and scrapings examined with the light microscope did not contain Malassezia furfur. These results indicate that ketoconazole is effective in the treatment of pityriasis versicolor, but the problem of protecting susceptible persons from infection and reinfection remains. PMID- 6255537 TI - The activity of ketoconazole in the treatment of onychomycosis. AB - Ketoconazole was administered orally in daily doses of 200 mg to 70 patients with onychomycosis. Complete recovery was attained by 48 patients, improvement of > 50% by 10 patients, and for three patients therapy failed. For the remaining nine patients the results could not be evaluated. The average duration of treatment was 7.5 months for disease due to Trichophyton species and 6.5 months for disease due to Candida species. There were no adverse effects or signs of toxicity attributable to the administration of ketoconazole. It is concluded that ketoconazole is a positive development in the effort to control the difficult problems presented by onychomycosis. PMID- 6255538 TI - Treatment of chronic mucocutaneous candidosis with ketoconazole: preliminary results of a controlled, double-blind clinical trial. PMID- 6255540 TI - Chronic mucocutaneous candidosis and other superficial and systemic mycoses successfully treated with ketoconazole. AB - Four patients with chronic mucocutaneous candidosis from early infancy were treated successfully with ketoconazole given orally. All thrush lesions were clinically and mycologically cured within a few days of treatment with 100-400 micrograms of ketoconazole daily; skin lesions were cured within a few weeks, and nails were cured after about three months of treatment. Delayed cutaneous hypersensitivity to candidin was acquired by the third month. Cellular and humoral immunologic responses were related to the suppression of Candida albicans antigen by ketoconazole. A fifth patient with chronic lingual granuloma due to C. albicans improved considerably. Favorable results also were seen in individual patients with oral and disseminated histoplasmosis due to Histoplasma capsulatum; laryngeal, pulmonary, and hepatic disease with continuous fever also due to H. capsulatum; pulmonary histoplasmosis due to Histoplasma duboisii; cutaneous sporotrichosis; and cutaneous blastomycosis due to Blastomyces dermatitidis and in three patients with favus due to Trichophyton schoenleinii; six of seven patients with tinea capitis due to Trichophyton violaceum (after one month of treatment); and four patients with infections due to Petriellidium boydii, Phialophora pedrosoi, or Beauveria species. All patients responded rapidly to 400 mg of ketoconazole per day given orally. Only the patient with hepatic histoplasmosis required 800 mg per day. Measurements of ketoconazole in the serum during treatment were useful in the evaluation of therapy. PMID- 6255539 TI - Treatment of chronic mucocutaneous candidosis with ketoconazole: a study of 12 cases. AB - Twelve patients with chronic mucocutaneous candidosis were treated orally with ketoconazole (doses, 200-400 mg daily) for a mean period of six months. Seven of the patients had one of the following abnormalities: congenital endocrinopathy syndrome, an autosomal recessive or autosomal dominant defect in which candidosis is not associated with endocrinopathy, or the malabsorption syndrome. All patients had fungal infections of the mouth, and 11 had onychomycosis. Two patients were also infected with dermatophytes. At the end of treatment, 10 patients were cured of oral infection, and 11 with nail infections showed significant improvement. Marked improvement of hand and foot infections was also recorded. Patients infected with dermatophyte fungi had the poorest responses to therapy. The mean (+/- SD) MIC for isolates of Candida albicans from eight patients was 0.95 (+/- 0.78) microgram/ml. Clinical and biochemical monitoring showed no toxicity, and no resistant fungi emerged during treatment. Results of this initial study of ketoconazole for treatment of severe and recalcitrant superficial infections indicate the need for further assessment of this drug, which appears to offer a simple, nontoxic, and effective treatment of fungal infections. PMID- 6255541 TI - Ketoconazole in vulvovaginal candidosis. AB - The efficacy of ketoconazole, a new oral antimycotic agent, was evaluated in an open trial. Forty-two nonpregnant women were selected on the basis of proven vulvovaginal candidosis and were divided into two groups. One group received 400 mg of ketoconazole per day for three days, and the other group received 200 mg per day for three days. Of the 26 patients who received the 400-mg dosage, 24 were cured; of the 16 patients who received the 200-mg dosage, nine were cured. No adverse effects attributable to the drug were found. PMID- 6255542 TI - Chemotherapy for the systemic mycoses: the prelude to ketoconazole. AB - Successful chemotherapy of the systemic mycoses now covers a span of more than 75 years and dates to the first reported use of potassium iodide for treatment of sporotrichosis. The second drug with efficacy was stilbamidine, and its currently available successor, hydroxystilbamidine isethionate, still has a role in therapy of some patients with nonprogressive blastomycosis of the skin. The introduction in 1957 of amphotericin B marked the first time there was an effective agent for such diseases as cryptococcosis, histoplasmosis, candidosis, and with lesser success, for coccidioidomycosis, mucormycosis, and aspergillosis. However, amphotericin B is nephrotoxic, depresses bone marrow (especially erythropoeisis), and, if patients are not monitored and controlled closely, the drug produces hypokalemic muscle weakness and cardiotoxicity. Flucytosine has a narrower spectrum of activity (cryptococcosis, candidosis, cladosporiosis, and chromomycosis) but a preferable route of administration (oral). Newer agents presently available are miconazole and clotrimazole; the latter is for topical use only. PMID- 6255543 TI - Ketoconazole: a new drug for the treatment of paracoccidioidomycosis. AB - Ketoconazole was administered orally to 13 patients with paracoccidioidomycosis. Therapy consisted of 200 mg per day for periods ranging from three to 12 months. All patients improved markedly, with healing of pulmonary, mucosal, and skin lesions. Patients exhibiting the latter two manifestations began to improve two weeks after therapy, and healing occurred within three months. Pulmonary lesions regressed at a slower pace and healed by fibrosis. Mycologic tests have corroborated the clinical improvement. Adverse effects were not observed; monitoring of renal, hematologic, and hepatic functions did not reveal any abnormalities. Five patients completed a year of therapy and were free of symptoms when therapy was discontinued. Of these patients, four were followed for several months and had no relapses; the fifth patient developed tuberculosis and died. The results indicate that ketoconazole is a safe and effective drug for therapy in the treatment of paracoccidioidomycosis. PMID- 6255544 TI - Ketoconazole in the treatment of paracoccidioidomycosis and histoplasmosis. AB - Ketoconazole was given orally to 33 patients with paracoccidioidomycosis and 23 with histoplasmosis. There were 55 men and one woman, and ages ranged from 28 to 67 years. Each patient had either the chronic disseminated or the chronic pulmonary form of disease. The diagnosis was established in 54 patients by culture of Paracoccidioides brasiliensis or Histoplasma capsulatum from lesions and in two patients by the clinical picture and results of serologic tests for histoplasmosis. The initial dosage was 400 mg per day. The dosage was reduced to 200 mg when a cure was achieved. The duration of treatment ranged from two to 18 months. Results of treatment were classified as very good (clinical and serologic cure) in 23 (41%) of the patients; good (clinical cure only) in 28 (50%); fair (partial improvement) in one (2%); and poor (no improvement) in three (5%). The results were not assessable in one patient who did not complete therapy. The three patients who did not respond to treatment had less than or equal to 0.19 microgram of ketoconazole/ml in their blood. The drug was well tolerated, and no side effects were reported. PMID- 6255545 TI - Treatment of paracoccidioidomycosis, candidosis, chromomycosis, lobomycosis, and mycetoma with ketoconazole: a brief summary. PMID- 6255546 TI - Therapeutic evaluation of ketoconazole in patients with coccidioidomycosis. AB - Eleven adult patients (seven men and four nonpregnant women) with coccidioidomycosis were treated orally with ketoconazole (R41,400). Two patients presented with disseminated coccidioidomycosis, six with pulmonary coccidioidomycosis, and three with the chronic cutaneous form of the disease. Diagnosis was established by culture of Coccidioides immitis and/or histopathologic identification of the fungus. All patients received 400 mg of ketoconazole per day for the first 10 days; afterwards four of them received 200 mg per day. Evaluation indicated that nine patients improved, one did not, and one could not be assessed. Treatment of coccidioidomycosis with ketoconazole appears to be reasonably effective and produces fewer adverse effects than does amphotericin B; however, further studies of the efficacy of this new drug are needed. PMID- 6255547 TI - Therapy of disseminated or pulmonary coccidioidomycosis with ketoconazole. AB - Oral therapy with ketoconazole for active disseminated or progressive pulmonary coccidioidomycosis was evaluated according to defined criteria of objective improvement for 39 patients, most of whom had received other antifungal chemotherapy. Minimal inhibitory concentrations of ketoconazole for isolates of Coccidioides immitis were below mean peak serum concentrations. Eighteen patients responded at all sites of disease, one patient failed to respond, and the others either are being evaluated or cannot be evaluated. Most patients who responded to therapy required more than three months of treatment before the response was clearly noted. Responses were seen with skin, soft tissue, skeletal, and pulmonary infection as well as other conditions. Reversions of cultures for C. immitis to negative and decreases in titers of complement-fixing antibody were common. One patient relapsed after a course of therapy of only four months. In general, patients with skin disease who responded required only 200 mg per day, whereas those with skeletal disease required 400 mg per day. Adverse effects were uncommon despite extensive monitoring and were generally limited to transient nausea (with vomiting in patients receiving 400 mg per day). The data show that ketoconazole appears to be a promising new drug for treatment of coccidioidomycosis. PMID- 6255548 TI - Treatment of coccidioidomycosis with ketoconazole: clinical and laboratory studies of 18 patients. AB - Ketoconazole was given to 18 patients with coccidioidomycosis. Fourteen had received prior antifungal chemotherapy with amphotericin B, miconazole, or both. Ten patients had pulmonary disease, two had meningitis, and six had extrameningeal disseminated disease. The initial dose of ketoconazole was 200 mg per day; it was later increased to 400 mg per day for some patients. All strains of Coccididioides immitis tested were sensitive to ketoconazole. Approximately 2 4 hr after an oral dose of 200 mg of ketoconazole, levels of the drug in blood peaked at approximately 2 micrograms/ml. Higher concentrations in blood were achieved with a 400-mg dose. Improvement was measured by physical examination, conversion of cultures previously positive for C. immitis to negative, decrease in erythrocyte sedimentation rate by 50%, and decrease in titer of complement fixation antibody by two or more dilutions. One patient died after one week of treatment with ketoconazole and could not be evaluated; two other patients with coccidioidal meningitis could not be evaluated. Six of nine patients with pulmonary disease showed radiographic improvement, and their sputum cultures, which had been positive, became negative. Four of the six patients with disseminated disease improved. There were few adverse reactions to ketoconazole, which can be safely administered for prolonged periods to patients with coccidioidomycosis. These findings suggest that ketoconazole may be effective for treatment of this disease and indicate that trials comparing the efficacy of ketoconazole with that of amphotericin B are warranted. PMID- 6255549 TI - An evaluation of two years of clinical experience with ketoconazole. PMID- 6255550 TI - [Secreting pituitary adenomas]. PMID- 6255551 TI - [Cytoplasmic transfer of hormonal information. Receptors and antihormones]. PMID- 6255552 TI - [Mode of action of parathormone on the metabolism of calcium and aluminium]. PMID- 6255553 TI - Reversible dementia and neuropathy associated with folate deficiency 16 years after partial gastrectomy. AB - A 57-year-old woman developed dementia and peripheral neuropathy 16 years after a partial gastrectomy (Billroth II). Serum cobalamin was 198 pmol/l (reference interval 150-550), and the vitamin B12 absorption test (Schilling) showed decreased absorption (1.7% without and 2.2% with intrinsic factor). In spite of 20 months' therapy with vitamin B12, the neurological symptoms progressed. Folate deficiency was suggested by a very low erythrocyte folate and a slightly abnormal FIGLU test. There were no other signs of general malabsorption. A few months' treatment with folic acid significantly improved the massive neurological manifestations which were verified neurophysiologically as well as histologically. A common role of vitamin B12 and folate in the development of neuropathy is suggested. PMID- 6255554 TI - Fluorescing particles (F-bodies) in lymphocytes in chronic lymphocytic leukaemia resembling Y-bodies. AB - The finding of fluorescing Y-body-like particles (F-bodies) in lymphocytes in patients with chronic lymphocytic leukaemia is reported. This finding may have diagnostic and pathogenetic implications. PMID- 6255555 TI - Production of DTH in the mouse to influenza virus: comparison with conditions for stimulation of cytotoxic T cells. AB - The kinetics of sensitization and elicitation of delayed-type hypersensitivity in mice to both infectious and non-infectious preparations of influenza virus was found to be similar to that of some protein antigens and to other viruses. Sensitization was achieved without added adjuvant. Maximum DTH was elicited in the footpad 6 days after sensitization. Adoptive transfer experiments showed that the effector cells were in the Ig-negative fraction of the spleen and were sensitive to anti-theta and complement. A comparison was made of conditions for the generation of DTH activity with cytotoxic T cells. The route of inoculation was important. With a high dose (10(3) HAU) of virus, subcutaneous inoculation was the most efficient and intravenous injection the least efficient for sensitizing for DTH, whereas the reverse was found for cytotoxic T-cell generation. Second, treatment of mice with cyclophosphamide (Cy) had differential effects. Preinjection of a large dose (200 mg/kg) into mice 2 days before sensitization with virus resulted in an increase in the DTH response and a 90% reduction in cytotoxic T-cell activity in the spleens of the treated mice. The Cy injected mice had reduced (70%) anti-haemagglutinin levels compared with the controls. This may be the explanation for the enhanced DTH response, since transfer of specific antibody to sensitized mice before injection of the eliciting virus substantially reduced the DTH response. Pretreatment with Cy did not affect the generation of DTH effector cells, since spleen cells from these and control mice had similar levels of activity. PMID- 6255556 TI - TCGF production for cloning and growth of functional human T lymphocytes. AB - In an effort to increase the potency of T cell growth factor (TCGF), several variables were examined for their effects on the production of TCGF. The following manipulations enhanced the potency of TCGF: first, the removal of adherent cells and addition of indomethacin to the producing cultures; second, irradiation with 1000 rads of the cells used to produce TCGF; and, third, the addition of Epstein-Barr virus transformed lymphoblastoid (LCL) cells. It was also noted that the addition of irradiated feeder cells increased the efficiency of limiting dilution cloning. PMID- 6255557 TI - [Changes in adenosine triphosphatase activity in the heart after administration of lanatoside C in irradiated and non-irradiated rabbits with acute cardiac overload]. PMID- 6255558 TI - [Dermatological complications in immunosuppressed patients after kidney transplantation]. AB - 205 recipients of renal allotransplants were evaluated either by clinical examination (n = 91) or by study of records (n = 114). More than 75% of the patients studied had dermatologic problems in the late post transplant phase, 25% having 2 or more such conditions. Steroid related complications were most often observed, i.e. cushingoid in 42%, acne in 26%, hirsutism in 19%, purpura in 12%, and rubeosis in 12%. Infections included warts (29%), herpes simplex (13%), herpes zoster (7%), and candidiasis (29%). 9 patients (4.4%) had skin carcinomas which were diagnosed on average 6.2 years after transplantation. The frequency of skin lesions during immunosuppressive therapy after renal allotransplantation requires regular skin inspections and information to patients on the potential risks. PMID- 6255559 TI - [Extracellular desoxyribonucleic acid in small cell bronchial carcinomas]. AB - In more than half of 30 small cell anaplastic lung carcinomas the authors have observed deposits of hematoxylinophilic material, mainly in the wall of small blood vessels. This finding has been interpreted as the result of dystrophic calcification. Histochemical evaluation, however, reveals the presence of deoxyribonucleic acid (DNA) and basic proteins (histones) in this material. Such extracellular DNA-deposits are not specific for small cell anaplastic lung carcinomas. They may be detected in other tumors, particularly retinoblastomas. Occurrence of extracellular DNA appears to be independent of size and spread of the tumor, cytostatic treatment and/or radiotherapy. High cellularity, high nuclear/cytoplasmic ratio and propensity to necrosis are common denominators for tumors displaying extracellular DNA. The cause of the phenomenon is unknown; the role of immunologic factors has been evaluated in the literature. The authors advance in alternative hypothesis involving tumor-induced inhibition of deoxyribonuclease activity. PMID- 6255560 TI - Clinical applications of nuclear cardiology. PMID- 6255561 TI - Endogenous substrate for cyclic AMP-dependent protein kinase in adrenocortical polyadenylated messenger ribonucleoproteins. AB - An endogenous polysomal cyclic AMP-dependent protein kinase specifically phosphorylates a 150,000-dalton peptide bound to an adrenocortical polyadenylated messenger ribonucleoprotein complex. There is a possibility that this protein is a physiological substrate of cyclic AMP-dependent protein kinase and that the phosphorylation and dephosphorylation of this substrate may be important in the translation control of adrenal polyadenylated messenger RNA. PMID- 6255562 TI - Effect of adenosine 3',5'-monophosphate on neuronal pacemaker activity: a voltage clamp analysis. AB - Bursting pacemaker activity in nerve cells can be modified for long periods by synaptic input of short duration. There is evidence that cyclic nucleotides may play a role in these modifications. The predominant effect of elevated levels of adenosine 3',5'-monophosphate in Aplysia neurons was an increased slope conductance to hyperpolarizing pulses, evident in voltage clamp records. A similar increase in slope conductance was seen as one component of maximum strength synaptic stimulation, which is consistent with the idea that cyclic nucleotides are important in the expression of synaptic alteration of bursting pacemaker activity. PMID- 6255563 TI - Binding and mobility of the cell surface receptors for 3,3',5-triiodo-L thyronine. AB - A fluorescent derivative of the thyroid hormone 3,3'-triiodo-L-thyronine binds to cultured mouse fibroblasts; such binding is saturable. Video intensification fluorescence microscopy indicates that binding occurs at the plasma membrane. Diffusion coefficients, obtained by fluorescence photobleaching recovery, are consistent with binding to a protein receptor on the cell surface. PMID- 6255564 TI - Pituitary intermediate lobe in dog: two cell types and high bioactive adrenocorticotropin content. AB - The pituitary intermediate lobe of most species is cytologically monotonous, but that of the dog is composed of two immunocytochemically distinct cell types. The predominant A cells are typical pars intermedia cells: they stain immunocytochemically for alpha-melanotropin and, more weakly, for adrenocorticotropin and beta-lipotropin. The B cells are like the corticotrophs of the anterior lobe: they stain intensely for adrenocorticotropin and beta lipotropin but not for alpha-melanotropin. The B cells may account for the high concentration of bioactive adrenocorticotropin measured in the canine pars intermedia, and may explain why in dogs adenomas causing Cushing's disease through hypersecretion of adrenocorticotropin can arise from the intermediate as well as the anterior pituitary lobe. PMID- 6255565 TI - A movable feast in the eukaryotic genome. PMID- 6255566 TI - 2-amino-4-phosphonobutyric acid: a new pharmacological tool for retina research. AB - Information processing in the vertebrate retina occurs in two separate channels known as ON and OFF channels. When intracellular electrophysiological recordings were obtained from the perfused retina-eyecup preparation of the mud-puppy (Necturus maculosus), the addition of 2-amino-4-phosphonobutyric acid to the bathing medium blocked all responses in the ON channel but left intact the OFF responses including OFF ganglion cell discharge. 2-Amino-4-phosphonobutyric acid blocks the light response of the ON bipolar cell by mimicking the endogenous photoreceptor transmitter. PMID- 6255567 TI - [Headaches and diet]. PMID- 6255568 TI - [Compliance with anti-inflammatory therapy in rheumatologic pathology among outpatients. Value of single daily dose]. PMID- 6255569 TI - [Medical treatment of arterial hypertension in children]. PMID- 6255570 TI - [Is it possible to diagnose the presence of a hepatoma in a cirrhotic patient early, using biological tests?]. PMID- 6255571 TI - [Prevention and treatment of recurrences of myocardial infarction. Results in 2026 patients monitored for 44 months in a group study]. PMID- 6255572 TI - [Clinical pharmacology and therapeutic results of a specific antagonist in disorders of gastroduodenal and peripheral motility]. PMID- 6255573 TI - [Synthetic estro-progestational (contraceptive) agents and cerebral ischemic complications: cerebral pseudo-tumours, thrombosis of intracranial venous sinuses. Apropos of 60 cases]. PMID- 6255574 TI - [relationship between nasal polyposis and bronchial asthma]. PMID- 6255575 TI - [Menopause and its treatment]. PMID- 6255576 TI - [Treatment of venous disorders in women]. PMID- 6255577 TI - [Depression: psychotherapy-chemotherapy]. PMID- 6255578 TI - [Diagnostic problems raised by the discovery of microscopic hematuria in adults]. PMID- 6255579 TI - [High dose antacids in gastroenterology, in 1980]. PMID- 6255581 TI - [Hyperprolactinemia : a misleading pathology too frequently unrecognized]. PMID- 6255580 TI - [Treatment of biliary lithiasis with ursodeoxycholic acid]. PMID- 6255582 TI - [When to prescribe an aminoglycoside in general practice?]. PMID- 6255583 TI - [Tobacco and vascular disease]. PMID- 6255584 TI - [Are sports ultimately beneficial or harmful to the heart?]. PMID- 6255585 TI - [The brain-scan in general practice]. PMID- 6255586 TI - [Role of synthetic antibacterial agents in respiratory pathology in children]. PMID- 6255587 TI - [Should we educate diabetic patients? Successes, failures, and their causes]. PMID- 6255588 TI - [Recurrent rhinobronchitis in children. Mechanism and treatment]. PMID- 6255589 TI - [Lupus in the elderly]. PMID- 6255590 TI - [Cutaneous and muscular unmyelinated afferent fibres. Clinical, histological and experimental study. Possible explanation of muscular cramps (author's transl)]. AB - Unmyelinated afferent fibres are the most numerous of the whole afferent component. Their function in nociception is now well established. However some recent data allow to think that their function is much more complex. Cutaneous unmyelinated afferences are evaluated in controls and in 3 groups of patients (painful neuropathies, painless neuropathies with hypesthesia, diabetic neuropathies). Amyelinic myelinic ratio is not in accordance with the gate control theory. Muscular afferent fibres are studied, especially the lateral gastrocnemius soleus nerve of cat. Their predominance is obvious. Our study was conducted by recording single unit activity from a micro electrod inserted in dorsal root ganglia. But 45% of unmyelinated fibres are not activated by various algesic stimuli. It is suggested that they have a function in cardio-pulmonary adaptation to effort and possibly segmental vascular control as homonymous reflex effect on moto-neuron. Their several properties are a possible explanation of muscular cramps. PMID- 6255591 TI - [Cerebral aneurysms complicating bacterial endocarditis. Seven cases (author's transl)]. AB - The authors report seven cases of cerebral aneurysms complicating bacterial endocarditis. The evolution was good in three cases, two of which without sequelae. The bacteries involved were staphylococcus, streptococcus, and enterobacter. The cardiopathy was mitral in four cases. Two patients presented an isolated focal neurological impairment, while the other five presented a severe coma either isolated (one case) or associated with focal neurological deficits (four cases). An intracerebral hematoma was diagnosed in five cases (four died). Only one patient was not operated. The surgical treatment was as follows: one carotid ligation (good result), two evacuations of intracerebral hematomas (both died), two evacuations of intracerebral hematomas with clipping of the aneurysms (one died, one had a fair result in despite of residual hemiplegia), one clipping of aneurysm (good result). Repeated cerebral angiographies should be systematically performed in cases of bacterial endocarditis in order to disclose and follow up cerebral aneurysms which may occur in this condition. Except in cases of emergency, surgery should be differed, in particular, in cases of proximal or multiple aneurysms. Aneurysms of the peripheral cortical arteries are more accessible to treatment and may be operated in the acute phase. PMID- 6255592 TI - [Effect of long-term therapy of essential hypertension on serum creatinine, electrocardiogram and eyeground status: a study of 71 patients over 7 years (author's transl)]. AB - 71 patients with essential hypertension have been followed for 7 years under effective anti-hypertensive therapy. Significant decrease in mean blood pressure was noted at the end of the first year and progressed linearly thereafter. Serum creatinine rose slightly, probably due to diuretics. Eyegrounds improved sharply during the first year, but deteriorated slightly thereafter: this may be due to increasing arteriosclerosis and validity of classification is questioned. Electrocardiogram improved during the first year, singularly in men: correlation with reduction in blood pressure was not clear. This discrepancy is discussed. It is concluded that improvement is sufficient to justify a continued treatment in this type of hypertension. PMID- 6255593 TI - [Renal malacoplakia. Report of two cases and review of the literature (author's transl)]. AB - The authors present a study of 38 cases of renal malacoplakia, two of which are personal. The clinical roentgenological and pathological data of such a histologically defined disease are reviewed. Nosological and physiopathological recollection is necessary before discussing management. PMID- 6255595 TI - [Pancreatic heterotopia of the stomach. Nine cases (author's transl)]. AB - A general review is done about 9 observations of pancreatic heterotopia of the stomach coming from statistics of 55 gastric benign tumors. The clinical, para clinical and anatomo-pathological notions are debated; the local resection is recommended: the pre and per-operative diagnosis are very difficult. PMID- 6255594 TI - [Encapsulating perihepatitis. Report of four cases (author's transl)]. AB - The authors report 4 cases of encapsulating perihepatitis, the macroscopic appearance of which corresponded to the morphological definition of the condition. The circumstances surrounding the diagnosis were very variable: association of ascites and porial hypertension, sub-obstructive syndrome due to associated encapsulating peritonitis, chance discovery at laparotomy or an unexpected finding at autopsy. The diagnosis was made pre-operatively in 2 cases by peritoneoscopy. All the patients had portal hypertension with, in particular, evidence of oesophageal varices. Three patients were treated surgically: hepatic decortication in all cases, combined in one another with umbilico-caval anastomosis. In all cases, the underlying perihepatic matrix produced epiglissonian fibrosis. However the inderlying hepatic lesions varied, ranging from definite cirrhosis to mild fibrosis. In one case, cirrhosis was associated with a hepato-cholangioma with nodular metastatic spread. The prognosis depended essentially upon the effects of general condition and the severity of hepatic lesions. In the light of cases reported over the past twenty years, the authors review the various clinical, pathogenic and therapeutic aspects of encapsulating perihepatitis. PMID- 6255596 TI - [Progressive chronic rubella encephalitis. Report of a personal case (author's transl)]. AB - This is a report on a now alive, 18 years old boy. He was affected by a progressive encephalitis which began between 7 and 12 years of age. The first signs were walking disorders and mental regression. The disease which developed during a few years led to a bed-ridden state and advanced mental deficiency. Strong biological arguments (analysis of the cerebrospinal fluid, virological study, brain biopsy) and comparison with several similar cases published before leading to the conclusion of rubella origin of this encephalopathy, despite of the absence of known history of congenital or acquired rubella in our case. PMID- 6255597 TI - [Parietal manifestations of thoracic actinomycosis. Results in five cases (author's transl)]. AB - The authors review five cases of actinomycosis with thoracic involvement, and emphasize the importance of parietal manifestations and their radiological appearance in the diagnosis of such cases. They refer particulary to the bone locations of the disease and mention rare oesophageal lesions and the development of systemico-pulmonary shunts. PMID- 6255598 TI - [Cadmium, zinc, pseudo-cholinesterase and aldolase blood levels in hypertensive and alcoholic patients. Preliminary statistical computerised study on 124 cases (author's transl)]. AB - Changes in blood-level of cadmium, zinc, pseudocholinesterase and aldolase were studied in 44 normal subjects, 40 hypertensive patients and 40 alcoholic ones. The highest serum concentration of cadmium and pseudocholinesterase, the lowest serum and blood concentrations of zinc, the lowest serum concentrations of aldolase were found in the two groups of patients, with still lower levels in alcoholic patients than in hypertensive ones. There was a negative correlation between zinc and cadmium levels in the three groups of subjects. There was a high correlation between systolic and diastolic blood pressure value and cadmium, and negative correlation between blood pressure and zinc blood and serum levels. PMID- 6255599 TI - [Detection of glial fibrillary acidic protein in central nervous tumors using an immunohistochemical method. Preliminary study of 33 cases (author's transl)]. AB - Thirty-two cases of human central nervous tumor and one experimental glioma were studied in fixed paraffin or epon embedded tissues using the peroxidase antiperoxidase method. The present study confirms the usefulness of immunohistochemical methods for the diagnostic evaluation of neuro-epithelial neoplasms. The authors also include some prognostic and histogenetic comments about glial tumors. PMID- 6255600 TI - [Mitral valve prolapse and severe rhythmic trouble (author's transl)]. AB - Mitral valve prolapse is usually a benign affection, and yet but rather seldom, severe rhythmic troubles and even a sudden death may happen. The authors relate an observation about a seventeen years old young man presenting syncopes caused by ventricular fibrillation fit. The existence of a mitral valve prolapse is demonstrated by phonomecanogram and specially by echocardiogram which shows a telesystolic depression of the small valve. The observation is followed by commentaries about the frequency and clinic of Barlow syndrome. The rhythmic troubles liable to accompany this mitral damage are analysed and so is the evaluation of the risk of a sudden death by ventricular fibrillation. PMID- 6255601 TI - [Severe catatonia, schizophrenia and hereditary coproporphyria. A case report (author's transl)]. AB - A patient with schizophrenia for many years presented after an attempted suicide, a severe drug-induced catatonia. In these circumstances, an hereditary coproporphyria was discovered. Clinical and pathophysiological interrelationships between the two syndromes are discussed. PMID- 6255603 TI - [An unusual case of uterine leiomyoma: exophylic grapelike development in the pelvic peritoneum (author's transl)]. AB - A 34 years old woman had a hysterectomy for persistent menorrhagias. The uterine vault was covered by an exophytic grape-like tumor measuring 10 cm in length, formed by little red nodules with focal adjacent lesions. This tumor is cytologically benign and of leiomyomatous nature on the ultrastructural study. The questions concerning diagnosis and prognosis of this case are discussed. PMID- 6255602 TI - [Two cases of buccolingual dyskinesia treated with tiapride (author's transl)]. AB - Two patients with Parkinson's disease developed buccolinguo-facial dyskinesias which were greatly improved after tiapride administration in association with antiparkinsonian agents. PMID- 6255605 TI - [Current status of allogeneic bone marrow transplantation]. PMID- 6255604 TI - [Pathophysiology of gastroesophageal reflux and esophagitis (author's transl)]. AB - Two new data explain pathophysiology of gastroesophageal reflux and esophagitis: first, the low esophagus pressure is altered in the reflux, second, the biliary salts act a part in the determination of esophagitis. New methods of explorations are proposed: esophageal manometric study, measure of intraluminal pH and soon perhaps radio isotope. That better understanding, those new explorations should allow to choose better than yesterday, therapeutic schemes. But many questions remain without answer. PMID- 6255606 TI - [Studies on liver abscesses (author's transl)]. AB - The authors report 25 observations of liver abscesses in the same service over a 5 years period. Diagnostic difficulties are pointed out and the value of echography, a simple and well tolerated examination, are emphasized immunologic studies allow the differentiation of the two types off liver abscesses i.e., pyogenic and amoebic, thus orientating their different treatments. The treatment of pyogenic abscesses (12 cases) is chiefly surgical, supported with suitable antibiotic therapy. Amoebic abscesses require medical treatment in collected abscesses of little or mean volume. In our series the number of patients requiring surgery is important (13 cases). This is due to persisting residual pouches or to the absence of well defined cliical improvement with medical treatment and the occurence of pre-burst or burst symptoms. PMID- 6255607 TI - Impact of Hodgkin's disease upon the immune system. PMID- 6255608 TI - Epidemiology of Hodgkin's disease. PMID- 6255609 TI - Gallium scans and serum angiotensin converting enzyme levels in talc granulomatosis and lymphocytic interstitial pneumonitis. AB - We have described two patients who had positive gallium lung scans with simultaneous elevation in serum angiotensin converting enzyme (SACE) levels. One patient had talc granulomatosis secondary to the intravenous injection of pentazocine, while the other patient had lymphocytic interstitial pneumonitis. We believe these are the first cases in which a positive gallium scan and elevated SACE levels were associated with these entities. PMID- 6255610 TI - Serological studies on possible causes of intra-uterine infections in Thai infants. AB - Serological tests for toxoplasmosis, rubella, cytomegalovirus (CMV), Herpesvirus hominis (HVH) infections syphilis (TORCHES) were carried out in 49 infants with showed signs of possible intrauterine infections and in 212 mothers and their newborn infants. The tests employed were ELISA for rubella and CMV infections, indirect haemagglutination for HVH infection and toxoplasmosis and RPR Macro-vue card test for syphilis. The immunoglobulin class of the antibody was also determined, and only infants with IgM antibody was considered indicative of intrauterine infection. It was found that 36.7% and 10.2% of infants with signs of intrauterine infections were positive for rubella and CMV antibodies and 19% had mixed infections of rubella, CMV, toxoplasma, syphilis and HVH. In contrast, only 6.1% of normal newborn infants had rubella antibody, 6% had HVH antibody and less than 1% had toxoplasma antibody, and none of them had CMV and treponema antibodies. Higher rate of seropositivities were found in their mothers, the percentage seropositivities for rubella, HVH, CMV infections, syphilis and toxoplasmosis were 19%, 12%, 2% and 1% respectively. PMID- 6255611 TI - [Pathogenesis of scanned spleen symptoms]. PMID- 6255612 TI - [Neuroendocrine disorders in brain concussion patients]. PMID- 6255613 TI - [Proton therapy, a new type of radiation treatment of hypothalamo-hypophyseal diseases]. PMID- 6255614 TI - Tamoxifen and hypercalcaemia. A case report. AB - A patient is reported in whom hypercalcaemia developed when adjuvant hormonal treatment with tamoxifen (Nolvadex) was instituted. The response to withdrawal of the drug and the recurrence of hypercalcaemia on rechallenge with tamoxifen make a causal relationship between hypercalcaemia and tamoxifen therapy probable. Some of the mechanisms of development of hypercalcaemia in cases of breast carcinoma are discussed, and the literature on hypercalcaemia and tamoxifen therapy is reviewed. PMID- 6255615 TI - Juvenile nasopharyngeal angiofibroma. AB - The juvenile nasopharyngeal angiofibroma, a locally invasive, non-metastasizing tumour of male adolescence, occurs sporadically throughout the world. Its histiogenesis remains uncertain and its management controversial. These facets of a troublesome and dangerous conditions are discussed and the experiences from handling 9 such tumours seen at Groote Schuur Hospital over a 4-year period (1976 1979) are presented. Surgical excision, using a wide field exposure and pre operative systemic oestrogen medication, is recommended as the treatment of choice. PMID- 6255616 TI - Control of sv40 replication by a simple chromosome in monkey-hamster cell hybrids. AB - Somatic cell hybrids produced between cercopithecoid monkey and Chinese hamster cells were used to assay susceptibility to SV40 viral infection in an attempt to define the primate factors that determine permissiveness to viral replication. These cell hybrids, which differed in their primate chromosome complement, were found to differ also in their ability to sustain viral replication. A correlation was found between an elevated SV40 viral replication and the presence of the chromosomes 11 in the rhesus monkey and 12 in the African green monkey which seem to be homologous to human 11. Preliminary studies also showed that the same chromosome seems to be responsible for the ability of the cell hybrids to rescue virus from rodent-transformed cells. PMID- 6255617 TI - Characterization of mitochondrial DNA in chloramphenicol-resistant interspecific hybrids and a cybrid. AB - We have examined the restriction endonuclease cleavage patterns exhibited by the mitochondrial DNAs (mtDNA) of four chloramphenicol-resistant (CAPR) human x mouse hybrids and one CAPR cybrid derived from CAPR HeLa cells and CAPS mouse RAG cells. Restriction fragments of mtDNAs were separated by electrophoresis and transferred by the Southern technique to diazobenzyloxymethyl paper. The covalently bound DNA fragments were hybridized initially with 32P-labeled complementary RNA (cRNA) prepared from human mtDNA and, after removal of the human probe, hybridized with mouse [32P]cRNA prepared from mouse mtDNA. Three hybrids which preferentially segregated human chromosomes and the cybrid exhibited mtDNA fragments indistinguishable from mouse cells. One hybrid, ROH8A, which exhibited "reverse" chromosome segregation, contained only human mtDNA. The pattern of chromosome and mtDNA segregation observed in these hybrids and the cybrid support the hypothesis that a complete set of human chromosomes must be retained if a human-mouse hybrid is to retain human mitochondrial DNA. PMID- 6255618 TI - Replicative potentials of various fusion products between WI-38 and SV40 transformed WI-38 cells and their components. AB - Hybrid cells derived from whole-cell fusions of replicating phase-II normal fibroblast cells (WI-38s) with SV40 transformed WI-38 fibroblast cells (CL-1s) demonstrated that the majority of the hybrid experimental cells still maintained a finite life-span. Approximately 2% demonstrated sustained and possibly indefinite replication. Experimental binucleate cells and subsequent hybrid synkaryons were also formed by fusing CL-1 karyoplasts into phase-II WI-38 replicating normal fibroblasts. In addition, viable cells were constructed from WI-38 fibroblast cytoplasts with CL-1 karyoplasts. Sustained replication was not observed in these crosses. PMID- 6255619 TI - Mapping of the herpes simplex virus DNA sequences present in herpes simplex virus type-1 thymidine kinase-transformed cells. AB - Analyses of the herpes simplex virus (HSV) DNA sequences which are present in three HSV thymidine kinase-transformed (HSVtk+) mouse cell lines have revealed that these cells contain relatively large and variable portions of the viral genome. Two of these cell lines do not contain the viral DNA sequences known to encode the early viral genes normally responsible for regulating tk gene expression during lytic HSV infections. This finding suggests that cell associated viral tk gene expression may be regulated by cellular rather than viral control mechanisms. In addition, we have compared the viral DNA sequences present in one unstable HSVtk+ cell line to those present in tk- revertant and tk+ rerevertant cell lines sequentially derived from it. Our results have shown that within the limits of sensitivity of our mapping approach, these three related cell lines contain the same set of viral DNA sequences. Thus, gross changes in viral DNA content do not appear to be responsible for the different tk phenotypes of these cells. PMID- 6255620 TI - Extradural nasal and orbital extension of glioblastoma multiforme without previous surgical intervention. AB - A case of extradural nasal and orbital extension of a glioblastoma multiforme in the absence of previous surgical intervention is presented. Such penetration by a glioma is rare due to the natural resistance of the dura mater. PMID- 6255622 TI - [Drug information: agents for the treatment of arrhythmias. 6. Heart electrophysiology]. PMID- 6255621 TI - CSF prolactin determination in patients following operation for pituitary tumor. AB - Serial cerebrospinal fluid (CSF) and plasma prolactin concentrations were determined from patients during prolactin stimulatory testing with thyrotropin releasing hormone or during pneumoencephalographic stress. Six patients had been operated on for suprasellar extension of pituitary tumor and one had been irradiated for suprasellar extension of a pituitary tumor. Prior to testing, four patients had had no clinical evidence of tumor recurrence and 3 patients had had tumor recurrence. One of the recurrent tumors had again extended into a suprasellar location. Basal CSF prolactin was undetectable in all patients who had had no recurrence. In 3 of the 4 patients without recurrence, however, prolactin became detectable in CSF during stimulatory testing. CSF prolactin values also increased during stimulatory testing in the patient with suprasellar recurrence of the tumor. A basal CSF-to-plasma prolactin ratio was 0.1 or less in all patients without recurrence. In the 2 patients with recurrence but without suprasellar extension, the CSF-to-plasma prolactin ratio was 0.18 or less. The patient with suprasellar recurrence had a strikingly elevated CSF-to-plasma prolactin ratio of 1.1. Thus, an increase of CSF prolactin during stimulatory testing does not necessarily indicate suprasellar recurrence of a pituitary tumor. However, an elevated CSF-to-plasma prolactin ratio appears to remain a valid indicator of suprasellar extension despite prior pituitary surgery. PMID- 6255623 TI - Developmental pattern of cAMP, adenyl cyclase, and cAMP phosphodiesterase in the palate, lung, and liver of the fetal mouse: alterations resulting from exposure to methylmercury at levels inhibiting palate closure. AB - Exposure to methylmercury (MeHg: 10 mg Hg/kg maternal body weight) on 12(6) (days hours) of gestation significantly delays palate closure in the Swiss Webster CFW mouse. The cAMP content and activity of adenyl cyclase and phosphodiesterase (PDE) were measured in the tissues of control and MeHg-induced cleft palates between 13(6) and 17(6) of gestation. Lung and liver were investigated similarly to determine if MeHg affected the adenyl cyclase system of the palate in a unique manner. In control palatal tissue, cAMP levels increased sharply from 13(22) (undetectable) to 14(6) (maximum). PDE activity increased similarly up to 14(2), but decreased 50% between 14(2) and 14(6). Since it has been reported that cAMP induces the synthesis of PDE, the difference in cAMP/PDE from 13(22) to 14(2) and from 14(2) to 14(6) suggests the localization of relatively high levels of cAMP in at least two separate compartments. Between 14(6) and 14(10), the adenyl cyclase activity of control palates decreased significantly. This rapid decrease suggests relatively high adenyl cyclase activity in the medial edge epithelial cells which undergo autolysis prior to shelf fusion (centered at 14(15). Maternal MeHg administration at 12(6) delayed the median time of palatal shelf rotation (14(13)) by 5 hours, and significantly altered the developmental pattern of the adenyl cyclase system. Thus, the increase in cAMP between 14(2) and 14(6) was abolished and the decrease in adenyl cyclase activity between 14(6) and 14(10) was delayed by almost 20 hours. These changes may be manifestions of a MeHg induced delay in medial edge epithelial cell differentiation. In a previous study, we observed that the fetal liver exhibits the highest MeHg concentration of all tissues. Since MeHg only slightly altered the adenyl cyclase system of the fetal liver compared to the lung and palate (in which MeHg uptake is considerably less), it may be that the effects of MeHg on palatal tissue are not due to a direct effect of MeHg on components of the adenyl cyclase system. PMID- 6255624 TI - Inappropriate ADH secretion caused by oat cell carcinoma and relieved by lung resection. PMID- 6255626 TI - Reoperation for bronchial carcinoma. AB - After a primary operation for bronchial carcinoma, 17 patients underwent reoperation for local recurrence or intrathoracic metastasis (nine squamous cell, five alveolar cell, and three adenocarcinomas). The average interval between the first and second operation was 23 months (range: six to 48 months). Twelve patients had a pneumonectomy after an initial ipsilateral lobectomy. Five patients underwent contralateral wedge excision after initial lobectomy or wedge excision. Three patients died within 30 days of the reoperation. Eight of the remaining 14 patients died subsequently, the time of survival averaging 18 months (range: three to 54 months). Six patients are still alive, two having survived their reoperation for more than five years. Reoperation for recurrent bronchial carcinoma is rarely performed, but it should be considered in all cases where patients survive operation for lung cancer if the primary operation was thought to be radical. PMID- 6255625 TI - Lung cancer in a defined geographical area: history and histological types. AB - Lung cancer was diagnosed in 446 patients during four years in a population living in a defined geographical area in northern Finland. The series comprised 420 men and 26 women, with a male/female ratio of 16.6:1. The diagnosis was confirmed histologically or cytologically in 431 cases (97%). Epidermoid carcinoma was the most common histological type of tumour in the men, followed by small cell anaplastic and adenocarcinoma, whereas in the women all these types were of equal frequency. Almost all the men, but only about half of the women, were smokers or ex-smokers. The amount smoked daily had no correlation with the histological type of cancer, whereas those patients who had started smoking early had relatively more Kreyberg group I tumours (epidermoid, small cell, and large cell carcinoma) than those who had started smoking late. Cancer was usually detected on the basis of symptoms, but 17% emerged from mass radiography or some health examination, and 12% from examinations for another disease. Fifteen per cent of the patients had no symptoms at the time of diagnosis, this being more common among the patients with epidermoid or adenocarcinoma than among those with anaplastic forms. PMID- 6255628 TI - [Changes in our view on the organization of the central nervous system. Have they significance for clinical neurology?]. PMID- 6255627 TI - Effect of venous occlusion and DDAVP injection on platelet aggregation and platelet cyclic AMP. PMID- 6255629 TI - Canine viral enteritis: prevalence of parvo-, corona- and rotavirus infections in dogs in the Netherlands. AB - After a brief review of the present knowledge about canine viral enteritis, the role played by parvoviral, coronaviral and rotaviral infections in contagious diarrhoea in dogs in the Netherlands is discussed. For this purpose a serologic survey, pathologic findings in dogs, and the demonstration of parvoviral antigen with an immunofluorescence test and with a newly developed haemadsorption-elution haemagglutination assay (HEHA) are presented. It is concluded that infections with canine parvovirus, coronavirus and rotavirus appear widespread among dog populations in the Netherlands. PMID- 6255630 TI - [Vaccination of 'non-swine' against Aujeszky's disease]. PMID- 6255631 TI - Effect of chronic lead treatment on GABA-ergic receptor function in rat brain. AB - The effect of chronic lead treatment on brain gamma-amino-butyric acid (GABA) ergic function has been studied in an attempt to correlate the clinical aspects of the chronic exposure to the metal with specific neurochemical alterations. [3H]GABA-specific binding and cyclic guanosine monophosphate (GMP) content have been measured in various rat brain areas and have been found to be increased in cerebellum and decreased in the striatum of rats after chronic lead treatment. The changes found in the GABA-ergic neurons were correlated with the different levels of lead exposure in rats. Our results indicated that lead selectively affects GABA-ergic function in various rat brain areas, inducing effects which are dose-dependent. PMID- 6255632 TI - Testosterone radioimmunoassay: rapid extraction technique for steroids based on kieselguhr mini-columns. AB - A technique for the rapid extraction of steroids from serum prior to their radioimmunoassay is described. The technique is based on the use of mini-columns filled with kieselguhr (Extrelut; Merck). The columns provide a means of achieving a rapid and precise extraction without the problem of emulsion formation and without the necessity to accurately measure organic solvent volumes. The technique is inexpensive, time saving and at least as precise as most conventionally extracted steroid assays. The results achieved correlate well with those of a conventionally extracted assay. PMID- 6255633 TI - Increased testicular 5 alpha-androstane-3 alpha, 17 beta-diol formation induced by treatment with [D-Ser (TBU) 6, des-Gly-NH2(10)] LHRH ethylamide in the rat. AB - While the intact male adult rats respond to LH with a predominant increase of testicular and plasma testosterone levels, the response to LH stimulation in animals treated with the LHRH agonist, [D-Ser(TBU) 6, des-Gly-NH2(10)] LHRH ethylamide is characterized by a major production of 5 alpha-androstane-3 alpha, 17 beta-diol. The marked increase of 5 alpha-androstane-3 alpha, 17 beta-diol levels in the presence of a 90% decrease of testosterone concentration strongly suggests that 5 alpha-reductase and 3 alpha-hydroxysteroid oxidoreductase activities are increased during testicular desensitization induced by treatment with the LHRH agonist. PMID- 6255634 TI - Clinicopathologic study of cytomegalovirus and congenital hearing loss: a progress report. PMID- 6255635 TI - A comparative study of Entamoeba histolytica (NIH :200, HK9, etc.), "E. histolytica-like" and other morphologically identical amoebae using isoenzyme electrophoresis. AB - Cultures of old, well documented strains of Entamoeba histolytica (NIH:200, HK9 etc.) have been compared with "E. histolytica-like" strains and, in turn, with E. moshkovskii, E. invadens and E. chattoni. They have been grouped according to their isoenzyme patterns. The "E. histolytica-like" organisms give patterns similar to E. moshkovskii and both of these are different from E. histolytica Groups I to IV. E. invadens and E. chattoni have easily distinguished characteristic isoenzyme bands. "E. polecki" is indistinguishable from E. histolytica. PMID- 6255636 TI - Protective effects of crude and chromatographic fractions of axenic Entamoeba histolytica in guinea-pigs. AB - Axenic amoebic antigen was chromatographed on Sephadex G-200. Two peaks divided into three fractions were obtained which were concentrated by lyophilization. Guinea-pigs were given a series of subcutaneous injections of crude Entamoeba histolytica antigen and its chromatographic fractions mixed with Freund's complete adjuvant. After three immunizing doses, the animals were challenged with intracaecal injection of a virulent isolate of amoebae (Strain No. H-25) and were killed seven days later. The antibody response was studied by indirect haemagglutination (IHA) and counter-current immunoelectrophoresis (CIEP) before intracaecal inoculation and at the time of killing. Fraction I, which had the highest molecular weight, stimulated high levels of antibodies in guinea-pigs and showed 92% protection. Only one animal of 12 inoculated had gross lesions and these were very mild. The caecal contents of three of the 11 animals without gross lesions were positive for amoebae but no tissue invasion was observed. Partial protection was observed with other antigens--30% with whole amoebae, 18% with Fraction II and 30% with Fraction III. In most there were multiple ulcers of the deep penetrating type and amoebae either penetrating and invading the muscular layer or the lytic process extending up to the muscular layer. In one animal, immunized with whole amoebic antigen, multiple hepatic lesions were also observed and trophozoites of E. histolytica were demonstrated histologically. PMID- 6255637 TI - Detection of alloimmune memory cells by chemical modification of the cell surface with mitogenic oxidizing agents. AB - The mitogenic oxidizing agents, neuraminidase and galactose oxidase (NAGO), and sodium periodate (IO-4) were used to induce the differentiation of human alloimmune memory cells. NAGO or IO-4 treatment of peripheral blood mononuclear (PBM) cells obtained from 10 sensitized potential allograft recipients resulted in the induction and augmentation of cytolytic activity to a D locus-defined lymphoblastoid cell panel (B cell panel) and to a HLA-disparate peripheral blood lymphocyte cell panel (PBL cell panel). The acquisition of cytolytic activity was determined in a 4-hr 51Cr release assay. Treatment of in vitro-primed PBM cells (alloimmune memory cells generated in primary long-term mixed lymphocyte cultures) obtained from normal subjects with NAGO or IO-4 also resulted in the induction of specific secondary cytolytic activity. In contrast, NAGO or IO-4 treatment of unprimed PBM cells from normal subjects did not result in the induction of cytolytic activity despite the extensive proliferation induced by such treatment. The strikingly similar results observed with PBM cells from sensitized patients and with in vitro-primed PBM cells suggest that in vivo- and in vitro-generated alloimmune memory cells can be detected by chemical modification of the cell surface induced by NAGO or IO-4. Furthermore, our findings indicate that alloantigen-independent activation of memory cells can be accomplished by treating the memory cells with the mitogenic oxidizing agents. PMID- 6255639 TI - The diagnosis and management of trophoblastic disease in a peripheral hospital. PMID- 6255638 TI - Identification of different subgroups of beta-receptors by means of binding studies in guinea-pig and human lung. PMID- 6255641 TI - Seasonal size variation in females of the Simulium damnosum complex in the Ivory Coast. AB - The thorax lengths of monthly samples of female S. damnosum s.l. caught between August 1975 and February 1977 at Danagoro in the Ivory Coast were measured. The blackflies could be separated into three species groups according to their external characters. Flies attributable to S. damnosum/S. sirbanum and S. soubrense/S. sanctipauli were common. S. yahense was occasionally found. The flies of the S. soubrense/S. sanctipauli group were on average consistently larger than those of the S. damnosum/S. sirbanum group within any one month. The mean sizes of these two groups varied in parallel from month to month and this variation was related to the rainfall in and around the drainage basin. This relation is discussed with respect to possible changes in the discharges of local rivers and their effects on larval development. PMID- 6255640 TI - Seroepidemiologic investigations of hepatitis in the tropics. A study on volunteers of the German volunteer service. AB - Sera from 349 volunteers of the German Volunteer service (GVS), who had lived in tropical or subtropical countries for about two years were tested for Hepatitis B surface antigen two years were tested for Hepatitis B surface antigen (HBS antigen), antibody to Hepatitis B surface antigen (anti--HBS), and antibody to Hepatitis A antigen (anti-HA) by radioimmunoassay. The findings were compared with those from a control group whose sex, age and occupational status corresponded with the volunteer group. The incidence of HBS-antigen was equal in both groups (1%). Anti-HA was found in 34% and anti-HBS in 19% of the volunteers but only in 26% and 7%, respectively, of the members of the control group. The greatest occurence of anti-HA was found among volunteers of the health service (46%) and technical service (35%) and of anti-HBS among the health service (29%), economic service (26%) and agricultural service (21%). Returned volunteers from West Africa showed a higher frequency (anti-HA 38%, anti-HBS 30%) than those from other countries (anti-HA 30%, anti-HBS 17%). The increased frequency of hepatitis corresponded with an increase in the morbidity rate from 25.5/10 000/year prior to service to 244/10 000/year during the service. PMID- 6255642 TI - [Marker chromosomes of murine cell lines]. AB - Using the C-method of chromosome staining four marker chromosomes were revealed in the transplanted murine line SC-1, one comparatively rare marker chromosome was shown in RAG line, small marker chromosomes occurred almost in all cells of RVP3 line. Marker chromosomes found in the studied lines by the C-method of chromosome staining make it possible to distinguish these lines from each other. PMID- 6255643 TI - [Ionic currents of neuroblastoma clone N18 A-1 cultured cells under potassium fluoride and phosphate intracellular dialysis]. AB - Ionic currents of cells of neuroblastoma clone N18 A-1 was studied under conditions when the internal medium was placed for artificial fluoride or phosphate solutions. The specific membrane leakage resistance was measured to be 8.1 +/- 2.6 kOhm.cm2 and 1.3 +/- 0.3 Kohm.cm2, respectively. The presence of usual sodium and tetraethylammonium sensitive potassium channels is demonstrated. Potassium conductance is shown to amount to 0.25--0.025 of sodium conductance. Dialysis of the cells by phosphate solutions induces a slow outward current, which is not inhibited by tetraethylammonium ions. PMID- 6255644 TI - [Properties of the sodium channels of the membrane of neuroblastoma clone N18 A-1 cultured cells]. AB - Ionic currents through sodium channels of dialyzed mouse neuroblastoma N18 A-1 cells were measured under voltage clamp conditions. The PNa/PK ratio evaluated by reversal potential shifts was 10.4 +/- 0.7. Parameters of steady-state fast inactivation curves (h--V) and peak sodium conductance curves (gNa--V) were determined. The inactivation kinetics had usually a two-exponential time course. The internal perfusion of cells by trypsin and pronase caused a slowing-down of the sodium current falling phase, pronase being more specific in this respect. An external application of the purified scorpion toxin in concentration of 1.42 X 10(-7) M leads to a fast and sharp slowing-down of sodium inactivation. The same toxin in concentration of 5 X 10(-6) M, applied internally was quite unaffective. Experimental results demonstrate similarities in the main features between the sodium channels of neuroblastoma cells and those of other excitable cell membranes. PMID- 6255645 TI - [Electron-acceptor (acid) properties of the contents of blood platelet intracellular granules and their significance for the reactions of these cells]. AB - The fluorescent marker method and measurements of aggregation were utilized to study the significance of the acidic intragranular space in blood platelets. Acridine orange is liberated from 5-HT granules after alkalinization by the ammonia ion which inhibits the induction of platelet aggregation by ADP and causes the platelet disaggregation. At low doses, ammonia ion enhances ADP induced aggregation. The transformation kinetics of 5-HT granules was investigated in the course of clot formation with a new instrument that simultaneously monitors the light transmittance (aggregation, clot formation) and fluorescence intensity (accumulation and liberation of fluorescent marker). These experiments provide the evidence that processes of fibrin filament sedimentation and fibrin-blood platelet interaction were followed by a liberation of fluorescent marker from 5-HT granules. PMID- 6255646 TI - Histopathology of carcinomas of the liver in mice fed perthane. AB - B6C3F1 female mice fed an average dose of 3,000 ppm of perthane for 2 years developed a highly significant incidence of hepatocellular carcinomas of the liver. Male mice fed 2,500 ppm perthane had a slight increase of carcinoma of the liver. Some of the carcinomas were well-differentiated; however, most were poorly differentiated or undifferentiated. Perthane-treated mice also had well and poorly differentiated cholangiocarcinomas and carcinosarcomas, neoplasms not seen in control mice. PMID- 6255647 TI - [30-minute ACTH test. Reproducibility and interpretation]. PMID- 6255648 TI - [Pseudohypoparathyroidism. Recent diagnostic aspects]. PMID- 6255649 TI - [Effect of oat brain on intestinal transit time, feces volume and excretion of fecal bile acids in healthy volunteers. A controlled double-blind study]. PMID- 6255650 TI - [Cytostatic chemotherapy and radiotherapy in small cell anaplastic lung carcinoma. Results of 2 prospective studies]. PMID- 6255651 TI - [Combination chemotherapy of the superior vena cava syndrome in small cell anaplastic lung carcinoma]. PMID- 6255652 TI - [Normalization of obstructive lung insufficiency in patients under cytostatic treatment for small cell anaplastic lung carcinoma]. PMID- 6255653 TI - [Prevention of early post-menopausal bone mineral loss. Controlled 2-year study of 315 women]. PMID- 6255654 TI - [Intradermal suturing compared with interrupted sutures in episiotomy]. PMID- 6255655 TI - [Intracutaneous suturing in episiotomy. Comparison of polyglycolic acid (Dexon) and silk sutures in skin]. PMID- 6255656 TI - Encephalitis and cerebellar ataxia associated with Epstein-Barr virus infections. PMID- 6255657 TI - [Functional state of the gonads in testicular tumors]. PMID- 6255658 TI - Male climacteric after orchiectomy in patient with prostatic cancer. AB - The case of a patient in whom prostatic cancer developed while on testosterone replacement following orchiectomy, is presented. the origin and management of climacteric symptoms in the male is discussed. PMID- 6255659 TI - [Testing of poultry for susceptibility to sarcoma viruses in the C subgroup]. AB - Experiments were performed to test the conventional chickens of the Ross I and Tetra-B broiler hybrid and the Shaver Starcross 288 and Slovgal laying hybrid for their susceptibility to the poultry sarcoma virus of subgroup C (B77). The chickens were inoculated six days from hatching and the first sarcomata began to appear at the inoculation spot on the fourth day. The first deaths were observed on the eighth day from inoculation, and the necropsy revealed frequent metastases. Regressive fluid was also found to develop in some cases. On the basis of the haematological examination of all hybrids, significant lymphocytopenia and heterophilia were determined; in addition to this, a significant drop in the basophile count was ascertained in the Tetra-B hybrid and a significant rise in the monocyte count was found in the Slovgal hybrids. Also, a frequent occurrence of a high number of large lymphocytes, a random occurrence of large thrombocytes, and individual myelocytes and metamyelocytes were also observed. The results suggest that the tested poultry represent progressive (highly susceptible) types of poultry, in relation to sarcoma virus of subgroup C. PMID- 6255660 TI - Bovine virus diarrhoea-mucosal disease virus: pathogenicity for the fetal calf following maternal infection. AB - Fifteen pregnant, bovine virus diarrhoea-mucosal disease (BVD-MD) antibody-free Jersey heifers were infected experimentally with a mixture of 10 cytopathic strains of BVD-MD virus isolated from cattle in Britain. Each cow was inoculated intramuscularly on gestation day 100 with a high or a low dose of virus grown in primary calf testis tissue cultures. None of the cows showed clinical signs of illness following exposure, but all had seroconverted within six weeks. Six fetuses, including one set of twins, died in utero following infection. Of these five were aborted between days 136 and 154; the sixth one was mummified and still retained at day 300. The remaining 10 fetuses survived to term, but all showed evidence of intrauterine growth retardation with or without gross malformation and/or dysmyelination of the central nervous system. Three were clinically affected with congenital nervous disease. Of the 10 liveborn fetuses, two had specific serum antibodies to BVD-MD. Non-cytopathic BVD-MD virus was recovered from all of the remaining eight. When non-immune cows become infected with BVD-MD virus in mid gestation: transplacental infection of the fetus will probably result; apart from the risk of fetal death, with or without abortion, there is a high probability of fetal mal-development which may not always be clinically obvious; the immunological competence of the fetus may be impaired; congenital infection is likely in a substantial proportion of liveborn calves. About one in 16 bovine fetuses in British herds are estimated to be at risk from BVD-MD virus infection. PMID- 6255661 TI - Isolation of feline herpesvirus 1 from a young kitten. AB - Five kittens exposed neonatally to older cats exhibiting fever with nasal and ocular discharge became ill and died within 10 days of the onset of illness. One kitten which died at 16 days old was examined post mortem and feline herpesvirus 1 was isolated from the brain, liver, lung and spleen. PMID- 6255662 TI - An outbreak of bluetongue in sheep in the Sudan. AB - An outbreak of bluetongue and the first isolation of the virus in the Sudan are reported. The disease occurred in sheep stressed by walking for five days when biting arthropods were prevalent. Estimates of the morbidity and mortality rates ranged from about 30 per cent and 2 per cent respectively in adult sheep to around 80 per cent and 100 per cent respectively in lambs. The virus was isolated by the inoculation of suckling mice and embryonated eggs with whole blood from febrile sheep. In a gel precipitation test it reacted with specific antiserum to type 10 BT8 strain. No other agent was isolated. Given the relatively mild nature of bluetongue in indigenous sheep, it is believed that the long walking stress coupled with exposure to sunlight might have aggravated the severity of the disease in this particular outbreak. PMID- 6255663 TI - Enzootic bovine leucosis virus in semen. PMID- 6255664 TI - Vaccination of guide dogs. PMID- 6255665 TI - Use of a modified live infectious bovine rhinotracheitis vaccine in the field. PMID- 6255666 TI - FPL vaccine and canine parvovirus. PMID- 6255667 TI - FPL vaccine and canine parvovirus. PMID- 6255668 TI - An enzyme-linked immunosorbent assay for enzootic bovine leukosis virus antibodies. AB - An enzyme-linked immunosorbent assay (ELISA) for detecting antibodies to enzootic bovine leukosis (EBL) virus is described and its sensitivity compared with that of the agar gel immunodiffusion test (AGIDT) using 198 sera collected in Great Britain. There was 95 per cent agreement between the ELISA and AGIDT, when sera with positive/negative ratio (P/N) values of 1 . 5 or greater were considered positive. A total of 259 out of 264 sera (98 per cent) collected in Northern Ireland had P/N values of less than 1 . 5, the remaining sera having P/N values of 1 . 5 and 1 . 6. As Northern Ireland is clinically and serologically free of EBL infection it is proposed that sera with P/N values of 1 . 5 and 1 . 6, which account for approximately 3.5 per cent of the total sera tested, are considered doubtful and should be tested by another serological test. PMID- 6255669 TI - Aujeszky's disease virus in meat. PMID- 6255670 TI - A micro-enzyme-linked immunosorbent assay for the detection of antibodies to infectious bovine rhinotracheitis virus. PMID- 6255671 TI - Diarrhoea in unweaned piglets associated with rotavirus and coccidial infections. PMID- 6255672 TI - Grassland management for horses. AB - The pasture needs for horses as compared to those for farm livestock are reviewed. The differing preferences of various types of grasses and other plants, and the patterns of grazing seen on"horse-sick" pastures, are discussed. Suggestions for practical management include frequent collection and removal of droppings, the use of grazing by cattle, adequate rest from horses and the application of cattle manure. Methods for controlling weeds and renovating horse sick paddocks are discussed and compared to ploughing up. Finally, the place of fertilisers is considered for use on pastures for horses. PMID- 6255673 TI - Rupture of digital flexor tendons of chickens after infection with reovirus. PMID- 6255674 TI - Milk fever controls: comparison of 1-alpha and vitamin D3 in conjunction with induced parturition. AB - The efficacies of vitamin D3 and its 1-alpha hydroxyl derivative (1-alpha) in controlling clinical milk fever, hypocalcaemia and hypophosphataemia in parturient cows have been compared. A corticosteroid was used in some cases to optimise and control the interval between prophylactic treatment and parturition. Our observations suggest that the combination of 1-alpha and corticosteroid was particularly valuable and could be used in the development of a successful prophylactic regime. This conclusion is supported by both clinical and biochemical measurements. PMID- 6255675 TI - Biology of simian virus 40 (SV40) transplantation antigen (TrAg). VI. Mechanism of induction of SV40 transplantation immunity in mice by purified SV40 T antigen (D2 protein). PMID- 6255676 TI - Viral polypeptides associated with the RNA replication complex in poliovirus infected cells. PMID- 6255677 TI - Pathogenesis of the slow disease of the central nervous system associated with wild mouse virus. II. Role of virus and host gene products. PMID- 6255678 TI - Frog virus 3 DNA is heavily methylated at CpG sequences. PMID- 6255679 TI - Bacteriophage P22 proteins specified by the region between genes 9 and erf. PMID- 6255680 TI - Relationship between virion-associated kinase-effected phosphorylation and transcription activity of vesicular stomatitis virus. PMID- 6255681 TI - Heteroduplex analysis of cloned rat endogenous replication-defective (30 S) retrovirus and Harvey murine sarcoma virus. PMID- 6255682 TI - [Cytomegalic inclusion disease in a newborn infant]. PMID- 6255683 TI - Cancer of the kidney: international mortality patterns and trends. PMID- 6255684 TI - [Mechanism of the autocatalytic formation of ferrihemoglobin by dimethylaniline oxide: analysis of the explanation of the structure of 2-dimethylamino-4-(N methylanilino)phenol]. AB - 1. The autocatalytic oxidation of haemoglobin to ferrihaemoglobin (methaemoglobin) by dimethylaniline N-oxide (DANO) has been further investigated with special emphasis on the condensation product of 2-dimethylaminophenol and N methylaniline. 2. From incubations of DANO with ferrihaemoglobin or ferricytochrome c, N-methylaniline, N,N-dimethylaniline, formaldhyde, 2 dimethylaminophenol, and 4-dimethylaminophenol were identified as reaction products. 3. The structure of the leuco compound, which is also formed in the incubation mixture, was shown by X-ray analysis to be 2-dimethylamino-4-(N methylanilino)phenol, a condensation product of N-methylaniline and 2 dimethylaminophenol. Chemical and physicochemical investigations confirmed this assignment. 4. The purple dye produced from the leuco compound by withdrawal of two electrons, and also found in the incubation mixtures, may be considered as a resonance hybrid of the two structures, 2-dimethylamino-N-methyl-N-phenyl-1,4 benzoquinone-4-imonium and 4-(methylphenylamino)-N,N-dimethyl-1,2-benzoquinone-2 imonium. 5. With clarification of the structures of the leuco compound and the purple dye, and of the mechanism of their formation, the autocatalytic formation of ferrihaemoglobin by DANO can now be described as shown in figure 5 (cf. Kiese and Renner 1976). PMID- 6255685 TI - Redox cycle of stable mixed nitroxides formed from carcinogenic aromatic amines. AB - 1. Of the carcinogenic aromatic nitrogenous compounds investigated, 10 out of 11 were found to be biotransformed in rabbit liver microsomal preparations to nitroxide radicals, as detected by ESR spectroscopy; with non-carcinogenic nitrogenous compounds only 2 out of 8 formed nitroxide radicals. 2. The radicals are stable mixed nitroxides formed by covalent binding of the aromatic nitroxide to endogenous constituents of the microsomal membrane with preservation of the nitroxide radical group (spin-trapping). 3. From the high chemical stability and the observed ESR spectra, spin-label-like structures can be deduced. 4. From this and the known one-electron redox properties of spin-labels, a redox cycle catalysing the production of reactive oxygen species and involved in tumour initiation and/or promotion by aromatic nitrogenous compounds is proposed. PMID- 6255686 TI - [Problems of extensive resection of the small intestine]. PMID- 6255687 TI - [Smoking or health]. PMID- 6255688 TI - [Developmental trends in drug research]. AB - A survey is given on the actual state of drug research and its developmental tendencies. Issuing from an estimation of the present and prospective health political and economic importance of the drugs the following main subjects of drug research are represented:--Influence on drug research by progressing of knowledge from biosciences,--traditional cooperation between synthesis, chemistry and biological test,--problems in the judgment of activity and security in the application of drugs (indirect side-effects of drugs),--problems in clinical testing of new drugs,--drug monitoring,--biopharmaceutical and galenic research conceptions. As to the fields mentioned the developmental tendencies are described as well as possible effects on the medicamentous therapy in practice are treated. PMID- 6255690 TI - [New viewpoints on the pathophysiology and pathogenesis of arterial hypertension]. AB - The pathophysiology and pathogenesis of the arterial hypertension can be explained from disturbances in the meshed regulating circle. Newer knowledge concerns the noradrenergic transformation of the excitation at the synapse. Concerning the humoral pressor systems we refer to the tonin-angiotensin-system, it is furthermore emphasized the disturbance in the sodium-potassium-transport on the membrane. The depressor systems -- prostaglandins, kallikrein-kinin-system -- will in future certainly bring newer knowledge concerning their participation in the pathogenesis of arterial hypertension. The practical importance of such findings should be taken into consideration in the formation of the long-term therapy of arterial hypertension. PMID- 6255689 TI - [Chronic pyelonephritis from a clinical viewpoint]. AB - The chronic pyelonephritis is an unspecific, bacterial, focal, interstitial nephritis with faculative participation of the pyelon. It is differentiated between an obstructive (secondary) and non-obstructive (primary) form. It is referred to the importance of risk factors and risk groups deriving themselves from this. Without doubt, the chronic pyelonephritis is the most frequent renal disease which is confirmed by new statistics of morbidity. The diagnostics still renders difficulties. In a course poor in symptoms it is not thought of the existence of the disease. For the rational dignostics in practice a step plan is recommended. In every case diagnostics should precede therapy. A therapeutic nihilism is to be avoided. A schematic treatment used without criticism and without taking into consideration individual peculiarities, secondary diseases, pregnancy and so on is to be abandoned. Short-term therapy and long-term prevention must be tuned one to another and possibly rationally combined. A plan for the long-term control in the renal dispensary is proposed. PMID- 6255691 TI - [Experimental studies on the usefulness of Dexon (polyglycolic acid) and our own modified suture method for suturing after tendon severing]. AB - The author had observed in experimental investigations the healing process that achillo-tenotomy in rabbits and a following suture with catgut or silk or DEXON. The suture after tenotomy was carried out with a circular suture of an own modification. Microscopic and macroscopic investigations showed a distinct bigger reaction of the connective tissue and more adhesions around the tenorrhaphy after catgut suture than after silk or DEXON suture. The mechanic investigations showed a clearly smaller tensile strength after a catgut suture than after silk or DEXON suture. Since DEXON sutures will completely resorb they are superior to the non absorbable sutures. PMID- 6255692 TI - [Paget-like reticulosis]. PMID- 6255693 TI - Effect of metopirone on pituitary gland of male squirrel, Funambulus pennanti (Wroughton). AB - 1. The ACTH cell type has been demonstrated for the first time in the hypophysis of the squirrels. These are large cells with homogenous cytoplasm and are more abundant in the anteromedian zone and in the peripheral portion than elsewhere. 2. A great hypertrophy and hyperplasia of the pituitary corticotrophs were observed in the experimental group at all the intervals. 3. Metopirone treated animals showed a moderate hypertrophy and degranulation of pituitary thyrotrophs. 4. By effect of metopirone, a marked regression of pituitary interstitiotrophs and total degranulation took place by 30 days treatment. The folliculotrophs did not show alterations. PMID- 6255694 TI - Effects of perineurally applied cytostatic, cytotoxic and chelating agents upon peripheral and central processes of primary nociceptive neurons. AB - After perineural application, the effects of mannomustine, cyclophosphamide, tetrameskylmannite, 6-mercaptopurine, azathioprine and d-penicillamine upon structure of peripheral nerves and the substantia gelatinosa Rolandi were studied by means of neurohistochemical techniques and compared to those of the microtubule inhibitors Vinblastine, Vincristine and colchicine. While the cytostatic and cytotoxic drugs induced only sporadic degeneration in the structure of the peripheral nerve and, accordingly, caused only a minor extent of transganglionic degenerative atrophy in the Rolando substance, the chelating agent d-penicillamine causes massive Wallerian degeneration after perineural application and, consequently, induces an extensive degenerative atrophy in the Rolando substance. The destructive effect of d-penicillamine upon conduction properties of the impaired nerve has been established also by means of electrophysiological recording. All the drugs studied differ fundamentally from microtubule inhibitors like the Vinca alcaloids that, by virtue of their blocking effect of axoplasmic transport, induce degenerative atrophy in the Rolando substance after perineural application without causing Wallerian degeneration in the peripheral nerve. Accordingly Vinca alcaloids are the most promising candidates as locally applied therapeutics in intractable pain. PMID- 6255695 TI - Subcloning of the histone DNA sequences of phage lambda Sam 7 h 22 in plasmid pBR 322. AB - The histone DNA sequences of the Hind III cluster of the sea urchin Psammechinus miliaris which are carried by the chimeric phage DNA of lambda Sam 7 h 22 have been subcloned in plasmid p BR 322. Due to this procedure single segments of the cluster have been separated from each other and are available as gene specific hybridization probes. PMID- 6255696 TI - Deoxyribonucleases in herpes simplex virus type 1 and 2 infected primary rabbit kidney cells. AB - In primary rabbit kidney cells infected with herpes simplex virus four different neutral deoxyribonuclease activities can be detected by means of the deoxyribonuclease assay in DNA-containing polyacrylamide gels following their separation by disc-electrophoresis. The method is suitable to follow independently the change in each activity of the different enzymes using only about 5 X 10(5) cells for each assay during the time-course of infection. Under these conditions one enzyme activity is constant, two disappear while the activity of a fourth one present only in infected cells, increases. PMID- 6255697 TI - ATP-dependent proton transport into vesicles of microsomal membranes of Zea mays coleoptiles. AB - ATP-dependent proton pumps were found in the vesicles of microsomal membrane fractions of maize coleoptiles. Two membrane fractions isolated by density gradient centrifugation were identified by the aid of marker enzymes and electron microscopic analysis. Membrane fraction A largely consisted of vesicles of smooth ER and of the Golgi complex, fraction B predominantly of vesicles of plasmalemma and rough ER. The pH-indicator, neutral red, was used to measure changes in pH in the vesicles after ATP addition. Due to the binding of protonated neutral red molecules (NRH+) to negative charges of the energized membrane, a strong metachromasy of NRH+-absorption can be observed. Therefore, in order to accurately measure delta pH a pH-dependent change in absorption of neutral red covering the whole NR-spectrum was set up as difference spectra. The commonly employed method of measuring delta A of neutral red at just one wavelength (525 nm) leads to entirely incorrect results. It could be demonstrated that the ATP dependent translocation of H+-ions into the interior of the vesicles was most efficient at pH 7. Acidification, which reaches its maximum 10--15 min after ATP addition, can be reverted by adding CCCP. An ATP-dependent proton-translocation into the vesicles of fraction B was also observed, however, the proton translocation is less than that found in fraction A in relation to the amount or protein found in each. The membrane fraction A displays a strong oxidation of NADH subsequently followed by an alkalization of the medium. This process cannot be reverted by adding CCCP. NADH oxidation at membranes of fraction A is consequently not an integral part of a redox-pump. A possible significance of the ATP-dependent proton pump in membranes of the ER and Golgi fraction of coleoptiles is discussed in connection with auxin induced elongation growth. PMID- 6255699 TI - [Glomus tumors of the head, neck and thorax. Clinical and angiographic experiences in the diagnosis of 11 cases]. PMID- 6255698 TI - ESR spectra of normal human serum after treatment with complement activating agents. AB - We describe the appearance of a free-radical signal in the ESR spectrum of normal human serum incubated with several complement activating agents. The intensity of this signal is dependent of dose of activating agents, time and temperature. Signals elicited by different complement activators differ in morphology and kinetics. Inhibition by treatment with EDTA and the presence of the signal in activated C 6-deficient rabbit serum suggest that the convertase forming steps of complement activation (C2 to 5) could be the source of free-radical containing molecules. PMID- 6255700 TI - [Excitation and inhibition mechanisms of local peripheral pain in man]. PMID- 6255701 TI - [Formation of a conditioned defense reflex in edible snails and changes in command neuron activity]. AB - After 5-15 pairings of food with electrical stimulation the snail exhibited escape reaction to food, while presentation of the same stimuli at random evoked no changes in feeding behaviour. This conditioned reaction, spontaneously restored after active extinction, was retained up to 20 days. Intracellular investigation of neural events underlying the same aversive learning on half intact preparation showed that responses of command neurones of feeding behaviour to food stimulus diminished slightly, while previously unresponsive command neurones of escape behaviour generated spike discharges in response to the same stimulus. PMID- 6255702 TI - [Role of intralaminar thalamic nuclei in strengthening inhibition induced by stimulation of the caudate nucleus]. AB - The influence of preliminary subthreshold activation of thalamic intralaminary nuclei on achievement of instrumental reflex and on inhibitory effects, caused by stimulation of the caudate nucleus head, were studied in chronic experiments on 5 dogs with a model of instrumental defensive conditioned reflexes, providing for maintainance of a given posture. It was shown that the preceding high-frequency electrostimulation of intralaminary nuclei activates motor components of the instrumental response (shortened latency, EMG and mechanogram of the response, increased amplitude of instrumental response) and significantly lowers threshold strength of the current, necessary for obtaining "caudate pause". The greatest increase in inhibitory influences, caused by stimulation of the caudate nucleus head, was observed when thalamic stimulation preceded stimulations, localized in the dorsolateral segment of the caudate nucleus head. The obtained data are discussed in aspect of Buchwald et al. hypothesis on the existence of "caudate loop". PMID- 6255703 TI - [Bidermal hepatoblastoma in an adult (author's transl)]. AB - Hepatoblastomas are more common in childhood but extremely rare in adults. A further case of hepatoblastoma in an adult is reported: The tumor consisted of two components, epithelial and mesenchymal ones. Both were well-separated from each other and showed different ways of metastasizing in to lymphatic vessels and lymph nodes or in to blood vessels and lung, respectively. It is concluded that hepatoblastomas of mixed type originate from two different cell types: The tubular and, sometimes, acinar malignant cells originate from the epithelium of the foregut and the osteo-osteoid-chondromatous malignant component is derived from mesenchymal cell of the coelomic wall. PMID- 6255704 TI - [Malignant alveolar soft tissue sarcoma (so-called malignant Abrikosoff tumor) of the right calf]. PMID- 6255705 TI - Factors influencing the effectiveness of adenovirus vaccination in lambs. PMID- 6255706 TI - Isolation of infectious bronchitis, infectious bursal disease and avian adenoviruses from chickens with nephritis-nephrosis syndrome. PMID- 6255707 TI - Prevalence of neutralizing antibody to porcine enterovirus serotype 2 strain BHZP/3 and its possible relation to atrophic rhinitis in pigs. PMID- 6255708 TI - [Trials to develop an immunoprophylaxis for transmissible gastroenteritis (TGE) of swine. IV. Replication and excretion of the vaccine virus TGE B1-300 following vaccination of sows and feeder pigs]. PMID- 6255709 TI - [Demonstration of a herpesvirus in Amazon parrots (Amazona aestiva and A. ochrocephala)]. PMID- 6255710 TI - [Differentiation between B. pertussis and B. parapertussis according to their fatty acid composition]. AB - The fatty acid composition of 3 B. pertussis strains and 2 B. parapertussis strains grown on casein-carbon agar (CCA) with 8% of sheep blood added and without blood, as well as B. parapertussis strain grown on beef-extract agar (BEA) has been studied by gas chromatography. The fatty acid profiles characteristic of B. pertussis and B. parapertussis were greatly different, as B. parapertussis has a considerable amount of methylene-hexadenocanoic acid, while containing less hexadecenoic and octadecanoic acids and more tetradecanoic acid. The fatty acid composition of 2- to 5-day Bordetella cultures grown on CCA with and without blood has no essential differences. Differences in the content of various fatty acids in B. parapertussis grown on CCA and BEA had no essential influence on the fatty acid profile. The specificity of the fatty acid composition of B. pertussis and B. parapertussis allows to use this characteristics for their differentiation. PMID- 6255711 TI - [Genetic study of cholera vibrios]. PMID- 6255712 TI - [Effect of exogenous adenosine-3,5-monophosphate on development of an immune response to sheep erythrocytes in mice]. PMID- 6255713 TI - [Electron transport particles from bovine heart as a test system in toxicological studies]. AB - 14 standard respiratory inhibitors and substances of toxicological interest were tested on the NADH oxidase and the succinate-cytochrome c oxidoreductase systems of beef heart electron transfer particles (ETP) in the presence and absence of human serum albumin (HSA). HSA did not influence the half-inhibition concentrations by cyanide, amytal and antimycin A. It had little effect on the inhibition by rotenone or carboxin, whereas the inhibition by free fatty acids and monoglyceride was greatly decreased. Lindan and DDT exerted a marked inhibition of the NADH oxidase system in the absence of HSA; the inhibition was weaker but still considerable in the presence of HSA. In the presence of HSA 10( 4) M DDT but not Lindan inhibited also the succinate-cytochrome c reductase system. The results show that ETP may be a useful test object in toxicological studies. PMID- 6255714 TI - The diagnostic reliability of cytologic typing in primary lung cancer with a review of the literature. AB - To evaluate the growing tendency in recent years to attribute more diagnostic reliability to cytologic methods, we investigated the accuracy of cytologic typing in specimens obtained from bronchopulmonary material by five different clinical sampling methods, comparing the cytologic diagnoses with the known histologic diagnoses. The study consisted of 232 cytologic specimens from 157 cases of primary lung cancer. Of the 232 specimens, 173 (75%) were correctly typed and 59 (25%) incorrectly typed with respect to the appropriate histologic diagnoses. When all sampling methods were considered together, the study demonstrated that well-differentiated epidermoid carcinoma and "oat cell" and spindle-polygonal anaplastic carcinomas yielded high cytologic typing accuracies. In poorly differentiated tumors, bronchioloalveolar cell carcinoma and bronchogenic adenocarcinoma, the correct cytologic typing was much lower. The different tumor types and their degrees of differentiation seem to be the decisive factors in cytologic typing accuracy. The findings of this study were compared with those of others and were found to be consistent with the results of even larger series of cases. For some types the typing accuracy was higher than that reported in other series, whereas for other types, e.g., adenocarcinomas, it was lower. PMID- 6255715 TI - Identification of viruses in the urine of renal transplant recipients by cytomorphology. AB - This study was designed to reassess the cytomorphology of viral infections in urinary cells obtained from renal transplant patients and to examine the association, if any, between these cytologic changes and the transplant rejection. A total of 2,354 cytologic specimens obtained from 91 renal transplant recipients was evaluated. A combination of techniques, including cellulosic filters, immunofluorescence, hemagglutination inhibition and electron microscopy, was utilized. Cytologic observations were correlated with the patient's clinical history. Thirty-eight patients revealed cytologic evidence of viral infections (herpes simplex, cytomegalovirus and papovavirus). These viral infections had distinct cytomorphology. Cytomegalovirus infection may manifest as intracytoplasmic, orangeophilic inclusions, in addition to the classical intranuclear inclusion. In the majority of renal transplant patients there appeared to be no relationship between the viral infection and the renal transplant rejection episodes. PMID- 6255716 TI - Cytopathology of papillary carcinoma of the thyroid by fine needle aspiration. AB - To delineate the cytologic presentation of papillary carcinoma of the thyroid, the fine needle aspiration smears were studied from 87 surgically proven cases. Six diagnostically useful findings were identified: papillary fronds, monolayered sheets, tissue fragments, intranuclear cytoplasmic inclusions, psammoma bodies and multinucleated giant cells. From 1,500 smears on "cold" nodules of the thyroid, 6 known false-negative and 4 false-positive diagnoses for papillary carcinoma were made. The estimated accuracy of the fine needle aspirate diagnosis of papillary carcinoma is 94%. PMID- 6255717 TI - Polymorph leucocyte function in uraemia and jaundice. AB - Biochemical measures of leucocyte function have been examined using cells from patients with jaundice or uraemia in order to elucidate how toxins might affect those cells and vital enzymes such as NADPH oxidase, myeloperoxidase and esterases. Indices of function were depressed in fulminant hepatic failure, in acute uraemia and in some cases of alcoholic cirrhosis. Conversely there seemed to be an adaptive enzyme increase in chronic uraemia and obstructive jaundice. The toxins which affect leucocyte iodination and myeloperoxidase have been defined. PMID- 6255718 TI - The effect of galanthamine hydrobromide on plasma ACTH in patients undergoing anaesthesia and surgery. AB - The effects of two anticholinesterases, galanthamine and neostigmine, on ACTH and, in some cases, cortisol were compared in 16 patients undergoing relaxant anaesthesia and surgery for varicose veins. The procedures produced increases both in ACTH and cortisol. Following administration of the study drugs to reverse the non-depolarising neuromuscular block, a statistically significant elevation of ACTH occurred in those patients who received galanthamine. It was concluded, therefore, that the rise in plasma cortisol is ACTH-dependent and not due to a peripheral cholinergic mechanism. PMID- 6255719 TI - Cyclic AMP and metabolic substrates following hemorrhage in awake and anesthetized rats. AB - The levels of several metabolites in plasma were studied during a period of 4 h in awake and barbiturate anesthetized rats after a blood volume loss of approximately 3% of b.w. Blood pressure was 70 mmHg (9.3 kPa) in the awake and 35 mmHg (4.7 kPa) in the anesthetized rats. Resting levels of plasma glucose, blood lactate and pyruvate and plasma cyclic AMP were higher in the awake rats than in the anesthetized rats. Bleeding caused an increase of plasma glucose in both groups. There was a more rapid increase in blood lactate and pyruvate as well as in plasma cyclic AMP levels in the awake rats than in the anesthetized rats. By contrast, plasma glycerol levels were unaltered by bleeding, and plasma FFA levels were decreased in both groups. At the end of the 4-h bleeding period plasma glucose was higher and blood lactate levels were lower in the awake rats. The initial changes in plasma metabolite levels appeared to be directly related to changes in plasma catecholamine levels. There were no differences in the relationship between the adrenaline level and cyclic AMP or glucose increase, suggesting that anesthesia did not alter beta-adrenoceptor sensitivity, but only catecholamine concentrations. The results also indicate that awake rats tolerate long-lasting blood volume loss better than anesthetized rats, because the sympatho-adrenal activation is more short-lasting. PMID- 6255720 TI - Localization of some steroidogenic enzymes in the ovary of the rabbit. AB - The distribution of delta 5-3 beta-HSD, peroxidase and cytochrome oxidase in immature, sexually mature and pregnant rabbit ovary has been studied histochemically. Corpora lutea are found only in pregnant rabbits. delta 5-3 beta HSD is present in the theca interna of mature follicles, corpora lutea and interstitial gland cells but is absent in the granulosa cells of both developing and mature follicles. The granulosa cells of mature and developing follicles, hypertrophied theca interna and the luteal cells all show intense cytochrome oxidase activity. Peroxidase is present in the corpora lutea only. It is suggested that delta 5-3 beta-HSD in the theca interna and interstitial gland cells is the enzyme responsible for steroid synthesis in the ovaries of immature as well as sexually mature rabbits, while peroxidase and delta 5-3 beta-HSD present in the corpora lutea together regulate luteal steroidogenesis during pregnancy. The intense cytochrome oxidase activity together with peroxidase and delta 5-3 beta-HSD confirms the observations that this tissue is a site of intense oxidative activity. PMID- 6255721 TI - Actin-myosin interaction in oriented F-actin filament system. AB - The decorated actin technique combined with the spin label method was used to study the interaction of skeletal muscle actin and myosin in synthetic filament system. If follows from the orientation dependence of the EPR spectra of the rigidly attached spin label in F-action filaments that the spin-label is sensitive to the dynamic state of the filaments. The interaction of myosin heads with actin reduces the intrinsic order of the F-actin filaments. The interaction seems to be cooperative. PMID- 6255722 TI - Mixed nemaline-mitochondrial "myopathy". AB - A 4-year-old boy suffering from a nonprogressive muscular weakness had a muscle biopsy which ultrastructurally showed large aggregates of nemaline bodies and mitochondria in myofibers; occasional concentric lamellated bodies were present as well. The mitochondria were mostly at the periphery of collections of nemaline bodies, less commonly in their central portions. The light microscopic features differed from those of either nemaline or mitochondrial myopathy and were somewhat reminiscent of multicore disease. Evidence suggestive of possible neurogenic origin of both rods and mitochondria is reviewed. PMID- 6255723 TI - Periodic units in the intracristal and envelope spaces of neuronal mitochondria. An artifact due to delayed fixation. AB - Ultrastructural study of the cerebral cortex and spinal anterior horns disclosed periodically repeating processes located in the envelope space or in the intracristal space of neuronal mitochondria. The alteration was observed in postmortem cases in which fixation was delayed either voluntarily or involuntarily, but was not present in postmortem or surgical specimens in which fixation was prompt. The change is interpreted as an artifact due to delayed fixation. PMID- 6255725 TI - Granulosa-cell and theca-cell tumors. The clinical picture and long-term outcome for the Radiumhemmet series. AB - Over the period 1923--72 a total of 305 patients with granulosa-cell, theca-cell tumor and mixed tumor were seen at Radiumhemmet. The commonest symptom was abnormal uterine bleeding. Twenty-three per cent of married women were nulliparous. The menarche seems to have occurred earlier in this group than in the general population. Eight of the granulosa-cell tumor group gave birth to 12 children after treatment for the tumor. Nineteen women with granulosa-cell tumor and 4 with thecoma had received radiotherapy earlier in life for benign lesions. The risk of endometrial cancer was approximately 10 times greater for the women with granulosa- or theca-cell tumor than for the general population. Two hundred and fifty-two patients were given both surgical treatment and radiotherapy. Fifty three received only surgery (37 granulosa-cell and 16 theca-cell tumors). None of the thecoma patients but 21 per cent of those with granulosa-cell tumor died from their disease. The 5-year survival for the latter group, all stages, was 85 per cent. PMID- 6255724 TI - The AB-variant of GM2-gangliosidosis. Clinical, biochemical, and pathological studies of two patients. AB - Clinical, neuropathological, and biochemical studies are reported in two children with the AB-variant of GM2-gangliosidosis. One patient had become symptomatic by 1--1.5 years, initially showing cerebellar signs, and then progressive psychomotor retardation, with hypotonia, spasticity, dementia, and macular cherry red spots, until death at the age of 4.5 years. The second patient showed an earlier onset of retardation and a more rapidly progressive course. At postmortem, the brains were of normal or near normal weights and displayed grossly only mild cerebral cortical and cerebellar atrophy, and mild pallor or attenuation of the white matter. Neuronal storage was widespread throughout the CNS, and both neurons and glia contained a variety of abnormal, membranous inclusions. Visceral organs were not involved. Ganglioside sialic acid was increased several fold in gray matter, with GM2 the predominant ganglioside species. N-acetyl-beta-glucosaminidase activities in serum, leukocytes, fibroblasts, and postmortem gray matter, assayed with an artificial, fluorogenic substrate, were normal, as were activities of other lysosomal hydrolases. PMID- 6255726 TI - Femoral and sciatic neuropathies after total hip arthroplasty. AB - Six patients with peripheral nerve lesions after total hip replacements were reviewed. The incidence of peripheral nerve lesions was six out of 825, i.e. 0.7 per cent. The neuropathies, four sciatic, one femoral and one combined femoral and sciatic, were due to damage by the reamer in one case, haemorrhage in two, whereas the cause was unknown in three patients. After conservative treatment and 1-5 years follow-up the recovery was classified as good in three, fair in one and poor in two patients. PMID- 6255727 TI - Inhibition of Na+,K+-stimulated ATPase in the cochlea of the guinea pig. A potential cause of disturbed inner ear function in terminal renal failure. AB - The frequent occurrence of sensorineural hearing loss in patients with chronic renal insufficiency prompted us to study the influence of chronic renal failure upon Na+,K+-ATPase in the inner ear of guinea pigs. Na+,K+-activated ATPase was defined as the ouabain-sensitive part of total ATPase, the activity of which was obtained in the presence of sodium, potassium and magnesium. A significant reduction of Na+,K+-activated ATPase was found in the inner ear of uremic animals. Such inhibition could be demonstrated as early as 12 hours after subtotal nephrectomy. An inverse correlation was found between serum creatinine levels and Na+,K+-activated ATPase. A similar inhibition of Na+,K+-activated ATPase in uremia is also found in other tissues (erythrocytes, renal tubules, intestinal mucosal cells, sarcolemma). Na+,K+-ATPase in the cochlea plays a key role in the maintenance of cochlear cationic gradients. It is suggested that inhibition of this enzyme system may contribute to the inner ear dysfunction in uremia. PMID- 6255728 TI - Advances in measurement of noise and hearing. PMID- 6255729 TI - Calculation of noise dose from time distribution of sound levels. AB - The noise from ten different sites in a machine factory was measured and cumulative time distributions of the sound pressure were constructed. From these distributions it is possible to calculate the energy mean level, the equivalent sound level as well as the average sound pressure level. Calculations based on knowledge of the times during which only a few sound pressure levels are exceeded give values deviating systematically from the exact value. Because of the systematic nature of the deviations corrections can be made for them. The accuracy of this method is relatively high. PMID- 6255730 TI - An impulse sound generator and some comparative experiments with different noise dosimeters. AB - An impulse sound generator has been constructed which gives the same sound pressure wave pattern during over 10(5) impacts with very small variations. This device has been used in evaluating the response of different types of noise dosimeters for impulse sounds. PMID- 6255732 TI - The reliability of Bekesy sweep audiometry recording and effects of the earphone position. AB - The hearing thresholds of subjects with hearing impairment of different severity were tested several times. The reliability of the hearing threshold measurements were analysed and compared to the inter-aural variations, the learning effects, the degree of noise-induced hearing impairment and the application of the earphones. The main factor determining the reliability of the hearing threshold is the application of the conventional earphone. A preliminary test-retest with the earphone adapted to an ear speculum for sound transmission to the external ear canal suggests that the precision of the Bekesy sweep hearing threshold measurement can obviously be increased in the frequency range of 2 to 8 kHz. PMID- 6255731 TI - Noise dose measurements with stationary and ear-borne microphones. AB - Precision measurement of noise doses with stationary and mobile, ear-borne, microphones were made on ten workers (emery-grinders, welders and platers). The workers selected in each group differed from one another in the amount they moved about during their working day. The differences in the reverberant field at their working places were also taken into account. Very large noise dose differences, up to 20 dB, between stationary and mobile dose measurements were found and it was not possible to find any correction factors for these differences. PMID- 6255733 TI - T and B lymphocytes in peripheral blood of children with infectious mononucleosis and tonsillitis. AB - The occurrence of T and B lymphocytes was investigated in children with infectious mononucleosis. It was shown that T and B lymphocytes participate in the increase in the number of lymphocytes during the acute phase of infectious mononucleosis. The increase in the absolute number of T lymphocytes was statistically significant (p < 0.001) as compared with control healthy children, and non-significant as compared with the absolute number of T lymphocytes in children with tonsillitis. The increased absolute number of B lymphocytes with infectious mononucleosis was statistically significant (p < 0.001) as compared with both control groups. Two of the children had a high percentage of atypical lymphocytes and positive titres of EBV-VAC antibodies, mostly comprising nil type lymphocytes. The findings suggest that infectious mononucleosis has probably a more varied immunological picture in children than in adults. PMID- 6255734 TI - Vaccine-associated poliomyelitis in an infant with agammaglobulinemia. AB - We describe a female infant with agammaglobulinemia who contracted vaccine associated poliomyelitis. Poliovirus type 2 was isolated from the initial stool specimen. In our patient, temporary changes in the cerebrospinal fluid resembled those in patients without immunodeficiencies, although gammaglobulin therapy had not yet been started. Pleocytosis was observed for a short time after viremia, but soon there was a return to normal without antibody production. PMID- 6255735 TI - Ultrastructure of human hepatocellular carcinoma. AB - Twelve human hepatocellular carcinomas (HCC) were studied ultramicroscopically. In the aspects of development of cytoplasmic organelles, well differentiated cancer cells were similar to the normal hepatocytes. On the other hand, poorly differentiated HCC cells contained little cytoplasmic organelle except for relatively developed rER and ribosomes. HCC cells showed not only several differentiations but also many degenerative changes, such as fatty metamorphosis, "dark" and "clear" cells, "fingerprint" formation and myelin-like figure, and the ultratructural alterations of the vessels among HCC cells could play one of the most important roles in causing these degenerative changes in human HCC cells. PMID- 6255736 TI - Malignant fibrous histiocytoma. A clinicopathologic study of 130 cases. AB - A clinicopathologic study of 130 cases of malignant fibrous histiocytoma (MFH) of the soft tissues is reported. This malignant neoplasm principally of middle and late adults occurred most often in the proximal portions of the extremities (48%) including the thigh and buttocks (35%). MFH may be subclassified into common (storiform and pleomorphic), myxoid, xanthogranulomatous, and giant cell types, the common type being accounted for 100 cases (77%) of the series. The prognosis was more favorable in patients with storiform and myxoid tumors than in patients with pleomorphic or other type tumors, the overall relative five-year survival rate being 48%. The depth of the tumor also affected prognosis with a significantly lower survival rate in deeply situated tumors. The rate of local recurrence of the tumor was 48%. Because of incomplete informations, metastasis was confirmed in only 26 patients and was most frequently to the lung (73%). In addition, electron microscopic, histochemical and tissue culture findings in limited cases are presented, concerning the histogenesis of the MFH. PMID- 6255737 TI - Experimental approach to fibrous histiocytoma. AB - A transplantable tumor was produced in syngeneic mice inoculated with transformed bone marrow macrophages (28-12- and L-18 cell lines). The tumor composed of proliferative spindle cells was arranged in a storiform pattern, and was similar to that of human fibrous histiocytoma. Electron microscopically, the tumorous spindle cells had fibroblastic characteristics, while functionally, the tumor cells had histiocytic characteristics, and consisted of a transitional form between histiocytes and fibroblasts. We consider the spindle cells to be facultative fibroblasts. This finding is compatible with the hypothesis that fibrous histiocytoma is derived from histiocytes. PMID- 6255738 TI - A light and electron microscopic study with comments on their relation to malignant fibrous histiocytoma and angiosarcoma. AB - Analysis of 365 cases of malignant soft tissue tumors revealed 83 cases of liposarcoma. The ages of the patients were distributed between 18 and 86 years with a mean average of 54.3 years. Approximately 50% of the cases were located in the lower extremity. Histologically, they consisted of 5 types; well differentiated (17 cases), myxoid (49 cases), round cell (3 cases), pleomorphic (11 cases), and mixed (3 cases). The appearance of lipoblasts of either the signet-ring type or mulberry (multivacuolated) type with displaced nuclei was the common characteristic feature for all types. Electron microscopically, lipid droplets were found inside of endoplasmic reticulum in lipoblasts, and abundant glycogen granules were seen in the cells containing only few lipid droplets. The lipoblasts were usually located close to the vascular wall in the interstitium, and findings suggesting an intimate relation between pericytes and lipoblasts were encountered. Although the differential diagnosis of malignant fibrous histiocytoma and liposarcoma was made possible by the appearance of lipoblasts in the latter, storiform pattern and histiocyte-like cells sometimes appeared in poorly differentiated liposarcoma. This tendency was also found in angiosarcoma. A close follow-up of recurrent cases revealed that there are actually cases of liposarcoma with malignant fibrous histiocytoma-like pattern and angiosarcoma with malignant fibrous histiocytoma-like pattern. It was considered that malignant fibrous histiocytoma-like figures can appear in various poorly differentiated sarcomas. PMID- 6255739 TI - Malignant fibrous histiocytoma with special reference to its differential diagnosis. AB - The histological diagnosis of malignant fibrous histiocytoma (MFH) seems to have become recently fashionable among pathologists, although its histogenesis and diagnostic criteria are not entirely settled as yet. For practical purposes the differential diagnosis with other easily mistakable mesenchymal tumors should be strictly made with great caution, because of variable histological features of this tumor. The authors attempted to elucidate the differential points from other tumors in a review of 189 cases of malignant soft tissue tumors. Some cases of carcinoma mimicking MFH were also reviewed. No single criterion for making the histological diagnosis of MFH was obtained. Its histological features and differential points from pleomorphic rhabdomyosarcoma and fibrosarcoma were tabulated. The recognition of a true tumor osteoid was emphasized as a single differential point between osteosarcoma and MFH often with fibrous areas mimicking osteoid. Renal cell carcinoma metastasizing to bone, which was misinterpreted as MFH on biopsy tissue, was also described and its differential point was stated. PMID- 6255740 TI - Effects of bis (tri-n-butyltin) oxide on endocrine and lymphoid organs of male rats. AB - A total of 160 Sprague-Dawley rats averaging in body weight, were used for histopathological and biochemical studies of toxicity of bis (tri-n-butyltin) oxide (TBTO). Short-term effects and long-term effects were examined. LD50 of TBTO by gastric tubing was 197 mg/kg. The effects of a single dose of TBTO were transient, and rapid recovery followed. TBTO at a a single dose of 100 mg/kg, or a total dose of 390 to 780 mg/kg in 13 weeks, or 780 to 1,560 mg/kg in 26 weeks, caused adrenal hypertrophy, flattening of the thyroid epithelium and atrophy of the thymus and lymph nodes. A single or repeated administration induced swelling and vacuolation of aldehyde-fuchsin-positive cells in the adenohypophysis. The immunohistochemical stainability of the cytoplasm of ACTH-cells was markedly depressed 24 hours after TBTO treatment, and that of the cytoplasm of TSH-cells was enhanced. Analogous an inverse relationship was also manifested in the hormonal levels of serum: levels of cortisol were elevated, while those of T-4 and TSH were depressed. PMID- 6255741 TI - Inhibition of hepatitis B Dane particle DNA polymerase activity by pyrophosphate analogs. AB - A DNA polymerase is associated with the core of the so-called Dane particles. The probability that this is the hepatitis B viral DNA polymerase offers the possibility of preventing hepatitis B multiplication by selective inhibition of this enzyme. We have previously reported that trisodium phosphonoformate (PFA) inhibits Dane particle DNA polymerase. Fifteen compounds with structural similarity to PFA and pyrophosphate have now been tested for inhibition of hepatitis B virus DNA polymerase in an attempt to define the structural requirement for the inhibition. Active structures have two acid groups at close proximity of which at least one is a phosphono group. Phosphonoformate and hypophosphare were the two most active inhibitors. The Ki value for PFA was 7.2 microM when dTTP was used as variable substrate, and the mechanism of inhibition was non-competitive. Phosphonoformate caused rapid shut-off of the polymerase reaction, indicating that it might inhibit elongation. The efficient inhibition of hepatitis B virus DNA polymerase by PFA and its low toxicity suggest that it could be used to inhibit hepatitis B virus multiplication in vivo. PMID- 6255742 TI - Cellular immune response in rabbits immunized with purified Visna virus. AB - Visna virus-sensitized lymphocytes were demonstrated in the peripheral blood of rabbits following immunization with purified, concentrated visna virus. Lymphocytes sensitization was maximal at about 2 weeks and fell to control levels in 5 weeks. A delayed-type cutaneous hypersensitivity to the virus was observed at 2 weeks and lasted for at last 9 weeks. Both reactions increased after a booster injection. Although sera from immunized rabbits had precipitating antibodies against visna virus protein P25, their lymphocytes were not stimulated by P25. However, there was a slight reaction to P25 in the skin test. Therefore, in contrast to the humoral immune response, P25 is apparently not the most active viral antigen in the CMI response in rabbits. PMID- 6255743 TI - Pregnancy specific beta-1 glycoprotein (SP1) in patients with trophoblastic disease: molecular heterogeneity and a "SP1 consuming factor". AB - The reactivity of sera from 19 patients with trophoblastic disease was analyzed in analytic immunoelectrophoresis using rabbit and human pregnancy specific beta 1 glycoprotein (SP1) antisera. Molecular heterogeneity of SP1 was demonstrated in crossed immunoelectrophoresis and a "SP1 consuming factors" was found in serum from a patient with choriocarcinoma. The "SP1 consuming factor" was precipitated by 1.65 M (NH4)2SO4. The results are discussed in relation to quantification of circulating SP1 patients with trophoblastic disease. PMID- 6255744 TI - Effect of chlorpromazine on ion transport induced by cholera toxin, cyclic AMP and cyclic GMP in isolated mucosa from hen intestine. AB - The isolated short circuit mucosa of chicken colon was established as an in vitro model for studies of the pathophysiology of diarrhoea and the mechanism of action of antidiarrhoeic drugs. Cholera toxin, 10(-7) M, added to the mucosal aide of the preparation, caused in a delayed reaction a pronounced increase of short circuit current (Isc). Cyclic AMP, which mediates the effect of cholera toxin (when added serosal) induced an immediate rise of Isc. Half maximal reaction was achieved at 3 mM cyclic AMP and maximal at 7 mM. The increase of Isc corresponded to the increase in the flux of chloride from serosa to mucosa. Unlike cyclic AMP, cyclic GMP almost equally stimulated sodium and chloride transport from serosa to mucosa. Unlike cyclic AMP, cyclic GMP almost equally stimulated sodium and chloride transport from serosa to mucosa, while the effect on Isc of the two nucleotides was additive. Chlorpromazine, which effectively reverses diarrhoea in cholera patients, totally normalized Isc after treatment with either cholera toxin, cyclic AMP or cyclic GMP. This reduction was achieved by a specific stimulation of transport of chloride from mucosa to serosa. The effect occurred also without previous treatment of the tissue with secretagogues (cholera toxin, cyclic nucleotides). No change in mucosal resistance was induced by chlorpromazine or cyclic GMP while it was reduced by cyclic AMP. PMID- 6255745 TI - Cyclic AMP, DNA and proteins in various areas of rat brain. AB - Values of cyclic AMP, DNA and protein content were determined in six regions of the rat brain: cerebral cortex, hippocampus, midbrain, thalamus with hypothalamus, cerebellum, and medulla. The obtained results indicated significant differences in the levels of protein in several areas of rat brain. There is some relationship between the changes in the content of DNA and cyclic AMP in these regions of the brain. These observations support the view that adenosine 3': 5' monophosphate can play a positive role in regulating DNA synthesis in rat brain tissue. PMID- 6255746 TI - Certain aspects of the mechanism of intestinal transport of sodium, potassium, calcium and magnesium in rats. AB - Intestinal absorption of sodium, potassium, calcium and magnesium was studied in rats by the method of intestinal perfusion using ouabain as an inhibitor of sodium-potassium dependent ATPase. At the same time the activity of ATPase and phosphatase were determined in homogenates of intestinal mucosa. A significant effect on the concentration of the determined ions was demonstrated in the transport of these ions, and also an unquestionable participation of intestinal ATPase in the direction and intensity of this transport. It was found that the multidirectional effect of ouabain on the transport of cations depended on their concentration. In the case of concentrations of cations similar to those in the mean food rations it has been demonstrated that ouabain increased the absorption of sodium, potassium and calcium and inhibited the absorption of magnesium. With a threefold higher ions concentration the absorption of potassium and magnesium was inhibited, without changing the transport of sodium and calcium. The possible explanation of the mechanism of these effects is discussed. PMID- 6255747 TI - Adrenergic reactions of sheep rumen in vitro. AB - The alpha and beta-adrenergic responses of the isolated muscle of sheep rumen were analysed by pharmacodynamic methods after administration of alpha and beta adrenergic agonists and alpha and beta-adrenergic antagonists. It was found that phenylephrine, and in a lower degree propranolol, stimulated contractions of isolated muscle of sheep rumen while adrenaline, noradrenaline, isoprenaline, phenoxybenzamine and regitine inhibited these contractions. Propranolol abolished the dilating (atonic) effect of catecholamines on the isolated muscles of sheep rumen and previous blockade of beta-adrenergic receptors with propranolol reversed the dilating effects of catecholamines. It is concluded that noradrenaline has an ambiceptor effect (similar to that of adrenaline) on the isolated muscle of the rumen. PMID- 6255748 TI - Adrenergic reactions of sheep rumen in vivo. AB - Pharmacodynamical analysis of alpha-adrenergic and beta-adrenergic reactions of sheep rumen was performed in vivo after administration of agonists and antagonists of alpha-adrenergic and beta-adrenergic receptors. It was found that phenylephrine, and in a lower degree propranolol, stimulated the motor activity of sheep rumen, while adrenaline, noradrenaline, isoprenaline, phenoxybenzamine and regitine depressed this activity. Propranolol abolished atonia produced by catecholamines in sheep rumen, and previous blockade of beta-adrenergic receptors with propranolol reversed the relaxing action of catecholamines on the muscular elements in the rumen. The experiments in vivo confirmed the adrenergic effects on the motor activity of the rumen of sheep obtained in earlier investigations on isolated muscles of the rumen. It is suggested that noradrenaline exerts an ambireceptro effect (similar to that of adrenaline) on the motor activity in sheep rumen. PMID- 6255749 TI - Effect of preceding physostigmine administration on neuromuscular transmission disturbances in rats caused by dichlorphos and phospholine. AB - The reported experiments were carried out on male Wistar rats. Under general anaesthesia with chloral hydrate in situ physiological preparations were made consisting of sciatic nerve and anterior tibialis muscle. Physostigmine was injected subcutaneously and was followed after from 15 to 60 minutes by intravenous injection of DDVP or phospholine. Physostigmine effect on the blockade of tetanic muscular contractions was studied after administration of these organophosphate inhibitors of acetylcholinesterase. At the same time, the effect of these substances on acetylcholinesterase was determined in the skeletal muscle. It was found that physostigmine in a dose of 125 microgram/kg protected the tibialis muscle against the development of blockade of tetanic response. The protective effect was greatest when the time between physostogmine injection and the subsequent administration of these organophosphate inhibitors was 30--40 minutes. In the same observation period the activity of AChE in the tibialis muscle of rats was found to be highest after physostigmine injection before administration of DDVP or phospholine. PMID- 6255750 TI - Demonstration of a proton gradient across the insulin granule membrane. PMID- 6255751 TI - Functional and metabolic effects of terbutaline and propranolol in fast- and slow contracting skeletal muscle in vitro. AB - The soleus, a slow-contracting, and the extensor digitorum longus (EDL), a fast contracting skeletal muscle from guinea-pig were prepared for isometric recording of sub-tetanic contractions in vitro. The contents of adenosine-triphosphate (ATP) and creatinephosphate (CP) together with their metabolites and the contents of lactate, pyruvate and cyclic adenosine-monophosphate (c-AMP) in the muscles were determined. It was found that the energy and redox state of the isolated soleus and EDL muscles is very stable and does not significantly differ from the normal state in vivo. Moreover, there were no consistent changes in these variables after treatment with terbutaline (a beta 2-adrenoceptor agonist) or propranolol or both. Thus, effects on energy metabolism do not seem to cause the changes in muscle contraction, characteristic for beta-adrenoceptor stimulation. On the other hand, the functional effects were accompanied by elevation of the c AMP level of the muscles. PMID- 6255752 TI - Effects of purified macrophage RNase on granuloma fibroblasts with reference to silicosis. AB - Two alkaline RNases, designated RNase 1 and RNase 2, were isolated from the culture media of silica-treated and non-treated macrophages. The yield of RNase from the medium of silica-treated macrophages was 30% of that from the non treated control. The effects of these RNases on cultured granuloma fibroblasts and on granulation-tissue nuclei were studied. RNase 1 inhibited thymidine incorporation into fibroblasts except at low concentrations, where it was observed to be stimulatory. RNase 1 also inhibited the protein synthesis of fibroblasts. The incorporation of cytidine into RNA in cultured fibroblasts was not affected by RNase 1, but the incorporation into isolated nuclei was decreased. In pulse chase experiments RNase 1 increased the release of cytidine, but not that of thymidine, from the cells. RNase 2 had no effect on the protein or nucleic acid metabolism of the fibroblasts or on the RNA metabolism of isolated nuclei, perhaps because of impermeability. These experiments confirm that macrophage RNase activity is able to regulate the metabolism of granulation tissue fibroblasts by increasing RNA degradation. Through this action it also regulates DNA and protein synthesis and other metabolic functions of those cells. PMID- 6255754 TI - Pseudotumor cerebri in pseudohypoparathyroidism. AB - A case of hypocalcemia with elevated serum PTH but normal renal response of cAMP and phosphate to PTH infusion is reported. The patient also had papilledema since many years probably due to long-lasting hypocalcemia. PMID- 6255753 TI - [Behavior of human erythrocytes under stress induced by a superoxide generator]. PMID- 6255755 TI - Biochemical aspects of SIF cell function in guinea pig and rabbit superior cervical ganglia. PMID- 6255756 TI - Opioid mechanisms in regulation of cerebral monoamines in vivo. PMID- 6255757 TI - Effects of cell culture conditions, nerve growth factor, dexamethasone, and cyclic AMP on adrenal chromaffin cells in vitro. AB - Adrenal chromaffin cells from young rats, newborn guinea pigs, and adult cattle were grown under various cell culture conditions. Nerve growth factor (NGF) elicited the outgrowth of neurite-like processes from rat, but not from bovine and guinea pig, chromaffin cells. Dexamethasone, dibutyryl cAMP, theophylline, and cholera toxin, which are known to augment intracellular cAMP, specifically inhibited neurite outgrowth. We propose that glucocorticoid hormones and mechanisms which act through an increase of cAMP are prerequisites for the acquisition and maintenance of differentiation and expression of an endocrine instead of a neuronal phenotype of adrenal chromaffin cells. PMID- 6255758 TI - SIF cells in cat sympathetic ganglia and associated paraganglia. PMID- 6255760 TI - On the nature of the receptors for various excitatory amino acids in the mammalian central nervous system. PMID- 6255759 TI - A model for excitatory transmission at a glutamate synapse. PMID- 6255761 TI - Radioreceptor binding studies with glutamate and aspartate. PMID- 6255762 TI - Regulation of hippocampal glutamate receptors: role of a calcium-dependent cysteine proteinase. PMID- 6255763 TI - Excitatory amino acid-induced changes in cyclic GMP levels in slices and cell suspensions from the cerebellum. PMID- 6255764 TI - Neuronal receptor sites for kainic acid: correlations with neurotoxicity. PMID- 6255765 TI - The role of biochemical factors in ventricular dysrhythmia accompanying ischemia. AB - Early malignant ventricular dysrhythmia induced by ischemia appear to depend on electrophysiological changes predisposing toward reentry. These changes are not readily explicable in terms of direct responses to hypoxia alone. Data from several laboratories make it increasingly clear that regional, heterogenous accumulations of noxious ions and metabolites play an important role. In addition to previously recognized factors including potassium, lactate, and hydrogen ion, both free and esterified fatty acid derivatives and metabolites of membrane phospholipids, particularly lysophosphoglycerides, have been implicated as potential mediators. Elucidation of the biochemical mechanisms responsible is of particular importance to development of prophylactic and therapeutic interventions with the needed specificity to be effective in reducing the incidence and severity of malignant ventricular dysrhythmia induced by ischemia and hence of sudden death. PMID- 6255766 TI - Novel aspects of skeletal muscle protein kinase and protein phosphatase regulation by Ca2+. PMID- 6255767 TI - Role of membrane lipid oxidation in control of enzymatic activity in normal and cancer cells. PMID- 6255768 TI - Studies on the processes of chromatin phosphorylation. PMID- 6255769 TI - Assembly of a polyoma-like particle from empty capsids and DNA in a cell-free system. PMID- 6255770 TI - The chemotherapeutic exploitation of virus-specified enzymes. PMID- 6255771 TI - The reactions and the structures of molybdenum centers in enzymes. PMID- 6255772 TI - Adenosine deaminase deficiency and severe combined immunodeficiency disease. PMID- 6255773 TI - The enzymology of 2,3-bisphosphoglycerate. PMID- 6255774 TI - The utilization of binding energy in coupled vectorial processes. PMID- 6255775 TI - Macrophage activation for nonspecific tumor cytotoxicity. PMID- 6255777 TI - A comparative investigation of antibody to swine vesicular disease virus using counter immunoelectrophoresis, serum neutralization and double immunodiffusion tests. PMID- 6255776 TI - Effect of levamisole on lysosomal enzyme release from polymorphonuclear leukocytes and intracellular levels of cAMP and cGMP after phagocytosis of monosodium urate crystals. AB - In order to study the influence of levamisole on lysosomal enzyme release, human polymorphonuclear (PMN) leukocytes were incubated with 0.5 mg/ml monosodium urate crystals. The release of neutral proteinase, beta glucuronidase, myeloperoxidase and lactic dehydrogenase as cytoplasmatic marker was measured. Preincubation of PMN with various concentrations of levamisole lasting 1 h resulted in a decrease of all enzymes released. Intracellular levels of both cyclic nucleotides--cAMP and cGMP--rose in PMN preincubated with levamisole, in comparison with untreated cells. PMID- 6255778 TI - Localizing insulinomas with combined radiographic methods. AB - Twenty-one patients with hyperinsulinism were studied to localize the source of the insulin production. Nineteen patients had pancreatic tumors and two patients studied after pancreatectomy had hepatic metastases. Of the 19 pancreatic tumors, 16 were identified by angiography. CT found six tumors in 14 patients studied while sonography correctly localized only three of 12 tumors. Neither CT nor sonography was positive in those patients with a negative arteriogram. Noninvasive imaging methods can localize large tumors and may be useful for detecting hepatic metastases. Angiography, however, remains the most accurate method for detecting smaller lesions. PMID- 6255779 TI - Gallium scanning in malignant fibrous histiocytoma. AB - Malignant fibrous histiocytoma (MFH) is a recently defined, well established clinical and pathologic entity. Five patients with MFH who had gallium-67 scans are described. An attempt is made to correlate the presence, absence, and extent of disease, as both primary and metastatic deposits showed avidity for gallium 67. After excision, patients with negative gallium scans were well, while metastatic disease was shown by gallium scans in two patients shortly before death. Gallium scanning is advocated for initial evaluation and follow-up of patients with MFH. PMID- 6255780 TI - Extension of neoplasm along the tract of a transhepatic tube. PMID- 6255781 TI - Radiation dose estimate to ocular lens in irradiation for glioblastoma multiforme. PMID- 6255782 TI - Dynamic CT densitometry of hepatic tumors. AB - Forty-two patients with hepatic tumors were examined by serial computed tomography (CT), using bolus injection of contrast medium. Scanning was at 15, 60, and 120 sec postinjection at a slice level containing the tumor. The densities of the tumor, liver, and aorta were sampled on these and on precontrast CT images. The tumors were divided into four types according to the pattern derived by sequential plotting of the density difference between the tumor and the liver parenchyma. Type I manifested rapid and prolonged high tumor enhancement, in type II the tumor was enhanced rapidly but then quickly became less dense than the liver, in type III there was no significant change over time in the density difference between the tumor and the liver, and type IV showed no, or very little, tumor enhancement. All cavernous hemangiomas belonged to type I while two-thirds of the hepatomas wer type II. There was a good correlation between tumor vascularity on CT and angiography. We suggest that dynamic serial CT scanning technique may be an improvement over the conventional drip-infusion technique in assessing liver tumors. PMID- 6255784 TI - Of viral nephritis. PMID- 6255783 TI - Cytomegalovirus myocarditis. AB - A male patient, aged 31 years, with a cytomegalovirus (CMV) myocarditis is described, who showed a high IgM antibody titer for cytomegalovirus infection of 1:1,024 and a rise of the titer for complement-fixing antibody from 1:< 16 to 1:256. CMV could be isolated from the urine. Investigations for other etiological factors were negative, and we assumed a connection between the cytomegalovirus infection and the myocardial involvement. PMID- 6255785 TI - Studies with aprindine. AB - Aprindine is a very effective antiarrhythmic agent with a narrow therapeutic toxic ratio. It has been used successfully in treating patients who have both supraventricular and ventricular tachyarrhythmias. Aprindine slows conduction in all cardiac fibers and suppresses digitalis-induced after-depolarizations. Voltage-clamp studies indicate that aprindine, in higher doses, suppresses the slow inward current in frog atria. In the dog subjected to coronary artery occlusion, aprindine may be arrhythmogenic, antiarrhythmic, or have no effect on the development of arrhythmias, depending on the temporal relationship between time of administration and time of occlusion. PMID- 6255786 TI - Introduction: calcium channel blockers. PMID- 6255787 TI - Comparative pharmacology of calcium antagonists: nifedipine, verapamil and diltiazem. AB - Calcium antagonists (slow channel blocking agents) are a very heterogeneous group of agents with dissimilar structural, electrophysiologic and pharmacologic properties. Nifedipine is a potent, long-acting vasodilator that has proved highly efficacious in relieving anginal symptoms caused by coronary vasospasm. In vivo, it exerts no myocardial depressant effects and has no antiarrhythmic properties. Treatment with nifedipine can safely be combined with administration of a beta receptor blocking agent. VErapamil prolongs atrioventricular (A-V) conduction (A-H interval) in a dose-dependent manner. It is the drug of choice for the treatment of reentrant supraventricular arrhythmias, irrespective of whether reentry occurs within the A-V node or through an accessory pathway (the Wolff-Parkinson-White syndrome). Verapamil is only moderately effective as an antianginal agent. Diltiazem is efficacious for the treatment of angiospastic angina, but its value as an antiarrhythmic agent remains to be delineated. PMID- 6255788 TI - Effects of actinomycin D on dexamethasone induced hepatic glycogen accumulation: morphological and biochemical observations. AB - Effects of inhibition of protein synthesis by actinomycin D (ACT) on the acute stimulation of hepatic gluconeogenesis and glucose-6-phosphatase (G6Pase) by the glucocorticoid, dexamethasone (DEX), in adrenalectomized (ADX) rats, were investigated using both morphological and biochemical means. Examination of ultra thin sections of liver in the electron microscope revealed that ACT, administered alone or with DEX, resulted in a failure of hepatic glycogen accumulation to occur. Smooth endoplasmic reticulum (SER) appeared similar to that of the ADX untreated animals, with occasional suggestions of increased amounts of membrane in ACT-treated animals. G6Pase activity in homogenates was increased, as was activation of the enzyme under all experimental conditions, when compared with ADX-untreated controls. The DEX-induced increase in G6Pase activity in SER failed to occur to any appreciable extent in ACT-treated animals. Plasma glucose levels increased slightly when ACT and DEX were present simultaneously. It is suggested that ACT countered the inductive effects of DEX on hepatic glycogen synthesis, but only partially suppressed acute stimulation of gluconeogenesis. A possible superinduction of G6Pase enzyme synthesis through increased efficiency of translation of extant mRNA is discussed. It is proposed that ACT inhibited the formation of appropriate SER membranes and/or other components necessary for glycogen accumulation. PMID- 6255789 TI - Stereological analysis of the guinea pig adrenal: effects of dexamethasone and ACTH treatment with emphasis on the inner cortex. AB - This paper describes the morphological responses of adult male guinea pig adrenals to dexamethasone (DEX) and adrenocorticotrophic hormone (ACTH), in both qualitative and quantitative terms. Most organelles and inclusions are affected, but their responses often vary in the different cell types examined: zona fasciculata externa and interna, and zona reticularis. Following DEX the volume of lipid droplets increases in cells of zona fasciculata externa but decreases in zona reticularis; smooth endoplasmic reticulum decreases in fasciculata externa but increases in reticularis. Following ACTH, exactly the opposite occurs. This strongly suggests differing functions for these subcellular entities in each cell type, particularly for the smooth reticulum, as well as for the cells themselves. The volume of the Golgi complex markedly decreases following DEX in all cells but increases only in zona fasciculata interna and zona reticularis following ACTH. These deeper cortical cells are known to secrete at least one sulfated steroid, dehydroepiandrosterone sulfate, and these changes in the Golgi complex strengthen the suggestion that the Golgi plays a role in sulfation of steroids. Mitochondrial volume and number decrease in all cells following DEX, supporting their role in steroidogenesis. Further decreases in their volume, accompanied by increases in their number following ACTH, may be related to a proliferation of mitochondria in response to ACTH. Changes in peroxisome volume and number, following DEX and ACTH, suggest a possible role for these organelles in steroid cell metabolism. Lysosomes decrease in volume in all cells following ACTH. This does not support the recently suggested concept that they play a role in steroid secretion. PMID- 6255790 TI - Pathology of alcoholism. PMID- 6255791 TI - Postirradiation malignant fibrous histiocytoma of the lung. Demonstration of alpha 1-antitrypsin-like material in neoplastic cells. AB - A metastasizing fibrous histiocytoma arising in the lung of a patient who received radiation therapy and long-term chemotherapy for malignant lymphoma is presented. Ultrastructural studies revealed fibroblast-like and histiocyte-like cells, cells of intermediate type showing ultrastructural features of both fibroblast-like and histiocyte-like cells, primitive mesenchymal cells, multinucleate tumor cells, and xanthomatous cells. The neoplastic cells showed dilated rough endoplasmic reticula with intracisternal accumulation of electron dense material forming lattice-like structures. Direct immunofluorescence staining of the neoplastic cells using antihuman alpha 1-antitrypsin showed specific activity, with fluorescent deposits exhibiting interlacing globular formations. These findings and their implications are discussed. PMID- 6255793 TI - Clostridium infection in mother and infant. PMID- 6255792 TI - A 6-year-old boy having hepatocellular carcinoma associated with hepatitis B surface antigenemia. AB - Hepatocellular carcinoma associated with hepatitis B virus (HBV) infection occurring in a boy who was 6 years 2 months old is reported. The patient is thought to have been infected with HBV by exchange blood transfusion (horizontal infection) in the neonatal period. Jaundice appeared eight months after birth. He was subsequently treated and follow-up with a diagnosis of hepatitis B surface (HBs) antigen (Ag)-positive chronic persistent hepatitis. His mother and other family members were HBsAg-negative. Postmortem examination revealed a multinodular growth of hepatocellular carcinoma of trabecular and solid pattern, mainly of the right lobe, complicated with mild fibrosis of the liver. Numerous HBsAg-positive hepatocytes demonstrated by orcein staining and the indirect immunoperoxidase method were present in the noncancerous area. This hepatocellular carcinoma is considered to have occurred within six years two months after HBV infection and not to have been associated with liver cirrhosis. The present case may be valuable for assessing the oncogenic properties of HBV and the incubation period of HBV infection before it develops into hepatocellular carcinoma. PMID- 6255794 TI - Studies on duodenal cyclic AMP content content in pancreatic disease after administration of pancreozymin and secretin. AB - Cyclic AMP (cAMP) output in the duodenal contents of 11 normal subjects, 18 patients with chronic pancreatitis, six convalescing from acute pancreatitis and five with pancreatic carcinoma was measured after a single dose of pancreozymin and secretin. The technic was indirect, utilizing recovery of duodenal contents by the Dreiling tube rather than direct measurements of fluid that was not contaminated by bile. In all patients groups, cAMP output reached a peak after this stimulation with a concomitant increase of bicarbonate and amylase outputs. A significantly decreased cAMP output was observed in all pancreatic disease groups compared to the normal group. Patients with chronic pancreatitis showed a slightly decreased cAMP output, considerably decreased bicarbonate output and normal amylase output. In acute pancreatitis cAMP output was reduced with normal bicarbonate and amylase outputs. In pancreatic carcinoma cAMP decreased significantly, bicarbonate output was moderately reduced and amylase output was normal. cAMP output in all groups studied did not correlate with either bicarbonate output or amylase output. PMID- 6255795 TI - Granular cell tumor of the esophagus. AB - Granular cell tumor is an uncommon lesion which is usually seen in the tongue, skin and breast. It has rarely been noted in the esophagus, this case being the 16th in the literature. Eleven of these patients had tumors removed at operation and four were found at postmortem examination. The tumor appears to be benign in character, although one case has been reported with metastases. Granular cell tumors of the esophagus should be surgically removed and may require wide excision because of fixation of the mucosa. The pathological characteristics of this tumor are reviewed. PMID- 6255796 TI - Extrahepatic biliary obstruction by hepatocellular carcinoma. AB - An unusual case of hepatocellular carcinoma that presented as an obstructing intraluminal hepatic and common bile duct mass is reported. PMID- 6255798 TI - Brief clinical report: hallux varus and preaxial polysyndactyly in brothers. AB - Two brothers with hallux varus of both feet are reported. One brother also had duplication/triplication of the great toes. The parents had no skeletal abnormalities or abnormalities of dermatoglyphics. PMID- 6255797 TI - HeLa cell identification by analysis of ribosomal DNA segment patterns generated by endonuclease restriction. AB - Restriction endonuclease analysis of HeLa cells and cells in which origins have been questioned provides evidence in favor of a HeLa cell origin for the questioned cells. Digestion of cellular human DNA reveals a variable ribosomal DNA (rDNA) fragment that is present in up to four discrete sizes. Cell lines of known and suspected HeLa origin contain only two size variants. This pattern of variability serves to distinguish HeLa-derived cells from others. Despite repeated passage and divergence of the HeLa phenotype and karyotype, the restriction pattern is remarkably constant. PMID- 6255799 TI - Therapy of endometriosis and dysmenorrhea. PMID- 6255800 TI - Toxic corneal epithelial edema from exposure to high atmospheric concentration of toluene diisocyanates. AB - Exposure to organic isocyanates in the atmosphere of a polyurethane-foam producing company resulted in microcystic corneal epithelial edema and conjunctival injection localized primarily in the palpebral fissure. The degree of microcystic edema and decreased visual acuity appeared to be related to location, length of exposure, ventilation, temperature, and amount of chemicals and premold stored. Clearing time varied with amount of exposure. Moderate amounts of microcystic edema caused an average fall of one line in the visual acuity. Pain was absent. The toxic effect of the isocyanates on the metabolism of the corneal epithelium may be the cause of the corneal epithelial edema. PMID- 6255801 TI - Experimental silicosis: morphologic and biochemical abnormalities produced by intratracheal instillation of quartz into guinea pig lungs. AB - Six months after intratracheal instillation of silica, histologic, ultrastructural, cytologic, and biochemical studies were performed on the lungs of guinea pigs. The tissue response consisted of both diffuse alveolar septal infiltration with interstitial fibrosis and granulomatous infiltration with nodular fibrosis. Ultrastructural studies confirmed the presence of a mixed inflammatory exudate in the alveolar interstitium (histiocytes, neutrophils, eosinophils, and lymphocytes) and the Type II lining of cell hyperplasia. The number of lung cells recovered by lavage and the proportions of neutrophils and multinucleated cells in bronchoalveolar cells were significantly greater in experimental animals (P < .05) than in controls (intratracheal saline). Total lung collagen and collagen synthesis by cultured lung tissue were also increased in the experimental animals. Since the response of guinea pig lung to intratracheal silica included pathologic features common to human silicosis and idiopathic pulmonary fibrosis, this model has the potential for improving our understanding of both of these important clinical disorders. PMID- 6255802 TI - Regulation of renal adenylate cyclase by parathyroid hormone. AB - This study reports the effects of the removal of endogenous PTH by thyroparathyroidectomy (TPTX) on the recovery of the reduced renal cAMP response to parathyroid hormone (PTH) in rats with chronically elevated PTH secondary to diets deficient in either vitamin D or calcium. After TPTX and infusion with a calcium-glucose solution of the vitamin D-deficient rat, calcium and PTH fell from 5.8 mg/dl and 2,509 pg/ml, respectively, to 4.8 mg/dl and 160 pg/ml at 48 h. There was a partial restoration of response to PTH, assessed by assay of renal cortical adenylate cyclase activity from 64% of control activity prior to TPTX to 84% of control activity at 48 h. When rats fed the diet deficient in calcium were TPTX, serum PTH fell rapidly from 2,811 to 200 pg/ml at 5 h with no further change at 21 h, whereas calcium did not change (5.3 mg/dl). PTH-dependent adenylate cyclase activity increased from 59% of control activity prior to TPTX to 87% at 5 h and 100% of control activity at 21 h after TPTX. Each diet produced similar increases in the serum level of immunoreactive PTH, and the rate of disappearance of the circulating hormone after TPTX was also similar for both groups of rats. The data indicate a slow, partial recovery of the enzyme response to PTH after TPTX of the vitamin D-deficient rat over the time period studied, whereas the recovery was rapid and complete in rats fed the diet deficient in calcium. PMID- 6255803 TI - Mechanism of enhanced lipolysis in adipose tissue of exercise-trained rats. AB - The effects of exercise training and food restriction on the regulation of lipolysis were studied comparatively in adipocytes isolated from male and female rats. Exercise training inhibited cell proliferation in parametrial, but not in epididymal adipose tissue, whereas it significantly reduced adipocyte size in both fat depots. Adipocyte capacity for responding lipolytically to epinephrine (10 microns) or to ACTH (1 micron) was markedly increased by exercise training. Enhanced lipolysis was also observed when cells isolated from exercise-trained animals were stimulated by bypassing with dibutyryl cyclic AMP (5 mM) or theophylline (5 mM) the early metabolic steps associated with hormonal activation of the adenylate cyclase complex. Significantly, binding of (-) [3H]dihydroalprenolol to cellular receptor sites was not affected by exercise training. It is therefore concluded that exercise training increases adipocyte responsiveness to lipolytic hormones at a metabolic step distal to stimulus recognition by adrenoreceptors, possibly at the level of protein kinases or lipases. Food restriction markedly reduced adipocyte size and partially mimicked the effects of exercise training on adipocyte proliferation and lipolysis. PMID- 6255804 TI - Serotoninergic system and circadian rhythms of ACTH and corticosterone in rats. AB - The circadian rhythms of plasma ACTH and corticosterone and of locomotor activity were explored in chronically cannulated female rats, after elimination of serotoninergic (5HT) innervation of the SCN (suprachiasmatic nuclei) either by stereotaxic lesion of the median and dorsal midbrain raphe nuclei (RX) or by local injection of SCN with the neurotoxin 5,7-dihydroxytryptamine (5,7DHT). Completeness of 5HT denervation was checked on serial sections of the hypothalamus either by the Falk-Hillarp technique or by radioautography. Neither lesion eliminated the intrahypothalamic 5HT system, which, however does not take part in the 5HT innervation of the SCN. In both experimental series, the circadian rhythms of the three parameters investigated were maintained in unchanged phase relationships compared to the sham-lesioned controls, and with respect to the photoperiod (12 light-12 dark). However, the estimated amplitudes of the ACTH rhythms dropped by 43% (RX) to 47% (5,7DHT) and their mean levels by 44% (RX) to 60% (5,7DHT), whereas the corticosterone rhythm displayed normal amplitude and its mean level rose by 24% (RX) or 38% (5,7DHT). In regard to locomotor activity rhythm, the most noticeable alteration was a 25-55% increase in the light-phase activity of both experimental groups with a correlative increase in the L/D activity ratio. The essential role of 5HT innervation of the SCN therefore seems to be to facilitate circadian control of the ACTH rhythm. PMID- 6255805 TI - Prostaglandin synthesis inhibitors reverse alpha-adrenergic inhibition of acute insulin response to glucose. AB - Prostaglandin E (PGE) has several effects on glucose homoeostasis and insulin secretion. The same events can be induced by alpha-adrenergic stimulation, which is known to stimulate PGE synthesis. To evaluate the hypothesis that PGE may be one intracellular mediator for certain alpha-adrenergic events, we examined the effects of a known PG synthesis inhibitor Sodium salicylate (SS) (40 mg/min iv) on the alpha-adrenergic effects of epinephrine (Epi) at two doses (3 and 6 micrograms/min) in normal male subjects. The lower dose of epinephrine diminished the acute insulin response (AIR) after a 20-g intravenous glucose pulse (control, 463 +/- 149; epinephrine, 97 +/- 38% of basal insulin, mean +/- SE, n = 6, P < 0.02); SS markedly augmented the AIR during epinephrine towards control values (339 +/- 137%; P < 0.02). In 12 subjects, the higher dose of Epi abolished the AIR. When similar studies were performed during a SS infusion, the AIR was partially restored (96 /+- 27% of basal insulin, n = 12, P < 0.01). Similarly, partial reversal of this alpha-adrenergic effect of Epi was observed with indomethacin, another inhibitor of PG synthesis. At both doses of Epi, SS augmented the glucose disappearance rate (KG) after the glucose pulse (P < 0.001). Sodium salicylate also increased basal glucagon levels (P < 0.05). In contrast, SS did not affect the glycemic response, the suppression of basal insulin levels, or the hemodynamic responses induced by adrenergic stimulation. We conclude that two prostaglandin synthesis inhibitors partially reverse the alpha-adrenergic inhibition of the AIR to glucose caused by Epi, without affecting other adrenergic events. The data are compatible with a role for prostaglandins in alpha-adrenergic events selectively in the pancreatic islet. PMID- 6255806 TI - Effects of vitamin D and diet magnesium on magnesium metabolism. AB - Effects of 6-9 days of vitamin D3 (D3), 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], 24,25-dihydroxyvitamin D3 [24,25(OH)2D3], or 1,24,25-trihydroxyvitamin D3 [1,24,25(OH)3D3] on Mg metabolism were studied in vitamin D-deficient (-D) rats. Mg absorption expressed as percent intake increased with 1,25(OH)2D3 and 1,24,25(OH)3D3. Urinary Mg (UMg) increased with no change in serum Mg (SMg) or Mg balance. 1,25(OH)2D3 was threefold more potent than 1,24,25(OH)3D3 in raising serum Ca and Mg absorption. In a separate experiment in pair-fed rats given D3, 1,25-(OH)2D3, or 1,24,25(OH)3D3, the diet contained either 0.03 or 0.2% Mg; 1,25(OH)2D3 and D3 lowered SMg after 3 days; UMg increased after 24 h to remain elevated. D3 and 1,25(OH)2D3 augmented Mg absorption; feeding 0.2% Mg lowered Mg absorption in -D animals. All sterols augmented Mg absorption in -D rats; both the earlier action of 1,25(OH)2D3 and 1,24,25(OH)3D3 suggests that 1 hydroxylation is necessary. Suppressed Mg absorption with 0.2% Mg in -D rats suggests two transport processes, with one vitamin D dependent. Higher UMg with decreased SMg with 1,25(OH)2D3 suggests reduced tubular reabsorption. PMID- 6255807 TI - Temperature effect on ADH response of isolated perfused rabbit collecting tubules. AB - The time course of the water permeability response to synthetic arginine vasopressin (AVP) was examined in isolated perfused rabbit collecting tubules. When experiments were conducted at 37 degrees C, addition of AVP in a concentration of 100 microU/ml increased hydraulic water permeability (Lp) from 18 +/- 4 X 10(-7) to 153 +/- 15 X 10(-7) cm x s-1 x atm-1. However, in contrast to results obtained at 25 degrees C, the Lp immediately decreased in spite of the continued presence of AVP, reaching half the peak value in 67 +/- 6 (SE) min. A similar decline was observed at 37 degrees C when a cyclic 3',5'-adenosine monophosphate analogue was added to the bathing medium. Corticosteroids greatly enhanced the peak water absorption but did not stabilize the subsequent response to AVP at 37 degrees C. A decline in diffusional water permeability measured in the absence of a transtubule osmotic gradient excluded the possible roles of cellular hypotonicity, increased cell volume, or osmotic water absorption in the unstable response to hormone. The peritubular membrane remained highly permeable to water, independent of AVP and temperature. Duration of exposure to 37 degrees C was more important than AVP in determining the unstable response. On the basis of these studies we conclude that isolated rabbit cortical collecting tubules progressively become insensitive to AVP at 37 degrees C, possibly due to alterations in the responsiveness of the urinary plasma membrane to cAMP. PMID- 6255809 TI - Niacin requirement for growth of axenic Entamoeba histolytica. AB - Niacin (nicotinic acid) was found to be essential for the cultivation of axenic Entamoeba histolytica. This vitamin requirement was also satisfied by nicotinamide. Panmede liver digest, a source of vitamins in the axenic medium was replaced with a dialyzed hot water extract of homogenized whole liver, supplemented with various growth factors. Cultured medium made with the liver extract and not supplemented with niacin failed to support continued multiplication of E. histolytica, but did support serial subculture when niacin was added. The concentration of added niacin required to achieve maximum growth was about 1 microgram per ml of medium. This is the first demonstration of a niacin requirement by the organism. PMID- 6255808 TI - Secretion of H+ and K+ by bullfrog gastric mucosa: characterization of K+ transport pathway. AB - The transport of K+ and H+ (both expressed as mueq/h) by in vitro chambered bullfrog (Rana catesbeiana) gastric mucosa have been studied under a variety of conditions such as anoxia, addition of p-chloromercuribenzene sulfonic acid (PCMBS) into the secretory solution, inclusion of ouabain in the nutrient solution, addition of thiocyanate (SCN-) into the mucosal solution, and replacement of nutrient chloride (Cl-) with sulfate (SO4(2-)), or gluconate (Gl). Anoxia reversibly reduced the H+ transport close to zero within 15 min and gradually reduces the K+ transport throughout the 2-h period of anoxia. The presence of 2.5 X 10(-4) M mucosal PCMBS in the histamine-stimulated mucosa increases the K+ transport, which is promptly reduced by changing the gas phase to 95% N2-5% CO2. Addition of ouabain to the nutrient solution of the histamine stimulated mucosa with PCMBS on the mucosal side significantly (P < 0.05) reduces the K+ transport within 60 min. Addition of SCN- to the mucosal solution of a histamine-stimulated mucosa with regular nutrient or O, K+ nutrient and 10, K+ mucosal solution reduces the H+ transport to near zero within 60 min. This SCN- inhibition can be reversed by elevating secretory K+. Substitution of nutrient Cl with SO4(2-) or Gl in the histamine-stimulated mucosa reversibly inhibits H+ transport and reduces K+ transport to a low level (0.7 +/- 0.05). Our data suggest that the K+ transport across the apical membranes of gastric cells is to a large extent a passive carrier-mediated process, and the transport of both K+ and Cl- are coupled at the apical membrane. PMID- 6255810 TI - Management of parotid gland neoplasms. AB - This clinical review presents a survey of the different types of epithelial neoplasms in the parotid gland. The incidence, histopathological classification, grade of malignancy, and staging system are discussed. Diagnostic procedures are reviewed and a scheme for treatment is proposed for the different types of epithelial parotid neoplasms. PMID- 6255811 TI - Lingual malignant disease of minor salivary gland origin. AB - The base of the tongue follows only the palate in frequency of involvement in minor salivary gland malignant disease. We present the clinical history and findings in three patients and review the relevant literature. Surgery is the preferred therapeutic modality, though the judicious use of radiation therapy may enhance local control of the disease. PMID- 6255812 TI - [Effect of synthetic progestins on carbohydrate metabolism and the content of anti-insulin hormones]. PMID- 6255813 TI - Effect of Bordetella pertussis vaccination in mice and the isolated tracheal response to isoprenaline. AB - The administration of Bordetella pertussis vaccine to mice has been associated with the development of an impaired beta-adrenoceptor responsiveness and in many respects has resembled human asthma. Trachea (n = 12) were isolated from Swiss Webster mice 5 days following the intraperitoneal administration of 2 x 10(9) B. pertussis organisms. The tracheal smooth muscle response to carbachol was measured and compared with that found in trachea from unvaccinated mice (n = 15). The contractile response was similar in both groups. The tracheal smooth muscle relaxant effects of isoproterenol were measured in these two groups. The EC50 value for isoprenaline (6.5 x 10(-7) M) in trachea from B. pertussis treated mice was significantly (P < 0.05) greater than that noted in the control animals (2.3 x 10(-7) M). These studies demonstrated that in tracheal smooth muscle isolated from B. pertussis vaccinated mice, the relaxant effects of isoprenaline are impaired. PMID- 6255814 TI - Passive paw anaphylaxis in the rat. Optimum conditions for use in studies on immediate hypersensitivity. AB - The difficulties involved in quantitating passive cutaneous anaphylaxis led us to examine the rat paw as a site for passive anaphylaxis and to define optimum conditions for passive paw anaphylaxis. Generation of homocytotropic antibodies in a number of different rat strains revealed that female Brown Norway rats were excellent producers of high titre antisera after only a single injection of antigen and Bordetella pertussis. Injection of ratpaws with diluted antisera followed by short (1-2 h) or long (72 h or more) sensitization periods showed that maximum paw swelling occurred 15 min after antigen challenge. Retention of tissue sensitizing capacity in the paw for greater than 35 days but loss of this capacity following heating of antiserum at 56 degrees C, indicated that the rat homocytotropic antibodies involved in passive paw anaphylaxis belong to the IgE class. Experiments using mepyramine, methysergide and diethylcarbamazine showed that 5-hydroxytryptamine is the most important mediator of passive paw anaphylaxis after both a short (2 h) and a long (72 h) sensitization procedure. Passive paw anaphylaxis in the rat is at least as easy to perform as passive cutaneous anaphylaxis, results can be obtained more rapidly and accurate measurement of paw thickness is not difficult. The procedure is a viable alternative to passive cutaneous anaphylaxis and may offer advantages over the latter method especially in the search for, and rapid assessment of, anti allergic compounds. PMID- 6255815 TI - Metabolic indices of pulmonary damage. Changes in angiotensin converting enzyme and alpha 1 anti-trypsin activity after cardiopulmonary bypass. AB - The activity of angiotensin-converting enzyme was measured in patients undergoing cardiopulmonary bypass and in a control group requiring thoracotomy for pulmonary surgery. The activity of the enzyme was higher in patients with cardiac disease, fell during operations involving cardiopulmonary bypass, but did not change during thoracotomy for pulmonary surgery. Possible reasons for these differences are discussed. The activity of another enzyme, alpha 1 anti-trypsin, did not change during cardiopulmonary bypass and no arteriovenous difference could be detected during or after operation. PMID- 6255817 TI - paH gradients in isoelectric focusing experiments at subzero temperatures. PMID- 6255816 TI - [Lung-converting-enzyme as a possible cell-maker in connection with the ultrastructural morphology in hypovolemic-traumatic shock (author's transl)]. AB - The lung shock syndrome, associated with a high rate of mortality, has been tested on an experimental animal model and was compared with clinical results. Consequently we obtained specimens as a base for morphologic examinations and LCE determinations. A modified flurometric method to determine the angiotensin converting-enzyme (LCE) has been developed. As a consequence a significant increase of the LCE-activity in shock also was noticed which might have been caused by the damage of the endothelial cells. The main part of this enzyme is situated on the surface of the lung endothelial cells and could be used as a marker enzyme. PMID- 6255818 TI - Design of a stable isotope dilution gas chromatography/mass spectrometric assay for cAMP: comparison with standard protein-binding and radioimmunoassay methods. PMID- 6255819 TI - A method for measuring anion transfer across red cell membranes by continuous monitoring of fluorescence. PMID- 6255820 TI - The isolation of intact adrenal chromaffin granules using isotonic Percoll density gradients. PMID- 6255821 TI - A one-step procedure for the isolation of fructose 1,6-bisphosphatase and fructose 1,6-bisphosphate aldolase from rabbit liver. PMID- 6255822 TI - Physical mapping of complex mRNA populations by "criss-cross" DNA-RNA hybridization. PMID- 6255823 TI - A rapid and efficient procedure for the purification of DNA from agarose gels. PMID- 6255824 TI - Chromatographic properties of silica-immobilized antibodies. PMID- 6255825 TI - Determination of hydrogen cyanide in blood using gas chromatography with alkali thermionic detection. PMID- 6255826 TI - Prejunctional and postjunctional cholinoceptors at the neuromuscular junction. PMID- 6255827 TI - Use of the artificial beta cell during anesthesia for surgical removal of an insulinoma. PMID- 6255828 TI - [Degos' malignant atrophic papulosis. Ultrastructural study of a new case]. AB - The authors report a case of Degos' malignant atrophic papulosis (MAP) with typical skin lesions from a clinical and histological standpoint. They stress in particular the ultrastructural study of skin biopsies which revealed numerous "paramyxovirus-like" tubulo-reticular structures in the endothelial cells, lymphocytes of the perivascular infiltrate, fibroblasts and keratinocytes. Although the significance of these inclusions remains open to discussion and is probably non-specific, their frequency in MAP is worthy of emphasis. PMID- 6255829 TI - [Histogenesis of lobular cancer of the breast. Histoenzymatic and ultrastructural study of a muciparous cell invasive epithelioma]. AB - A comparative light microscopy, histoenzymological and ultrastructural study enabled the authors, in a case of invasive lobular carcinoma of the breast, to emphasise certain special morphological traits of this tumour type and to make a contribution to the understanding of its histogenesis. By light microscopy, the only special features of the case were the abundance of mucus secreting tumour cells in the perilobular infiltrating zones and in the stromal texture with marked perigalactophoric hyalinosis and active elastic neogenesis. From an ultrastructural standpoint, intralobular malignant zones contained epithelial type cells, rich in microfilaments and with numerous desmosomal junctions. Two other cell types were identified at the periphery of the lobules. On consisted of round cells with intracytoplasmic cavities filled with mucus (signet ring cells). This group, in common with the intralobular cells, contained abundant amounts of alkaline phosphatase. The other consisted of elongated "pseudo-fibroblastic" cells, rich in microfibrils and in granular ergastoplasm with secretion at points of contact of collagen and elastin. These cells showed marked ATPase activity. They no doubt represented "hybrid" cells, intermediate in terms of their morphology and enzyme activity between myoepithelial and epithelial cells. These findings would thus appear to offer arguments in favour of the double cell origin -- duct and myoepithelial -- of lobular carcinoma. PMID- 6255831 TI - Inactivated vaccine for parrot herpesvirus infections (Pacheco's disease). AB - Four tests of an inactivated emulsified vaccine against a herpesvirus infection (Pacheco's disease) in bodgerigars demonstrated that an effective vaccine could be produced with concentrated virus. Virus was propagated in chicken kidney cells, and cells and fluid were harvested 3 to 5 days after inoculation and sonicated. The virus was concentrated 100 x by centrifugation to produce a multiple emulsion vaccine that was protective against IM challenge exposure with live virus. The serologic response after vaccination was negligible, and many survivors to virus challenge exposure did not show a positive titer. PMID- 6255830 TI - Combined dexamethasone suppression and cosyntropin (synthetic ACTH) stimulation test in the dog: new approach to testing of adrenal gland function. AB - A combined dexamethasone suppression and cosyntropin (synthetic ACTH) stimulation test was developed in the dog so that information concerning pituitary gland (hypophysis) and adrenal gland competence could be provided in a single trial, during a short time span. Treatment of dogs with dexamethasone (0.1 mg/kg, IM) resulted in total suppression (below assay sensitivity or < 10 ng/ml) of plasma hydrocortisone (cortisol) at postinjection hour (PIH) 2 in 100% of the dogs, whereas suppression was inconsistent at PIH 1. Cosyntropin (0.5 U/kg, IV) administration to normal or dexamethasone-suppressed dogs increased plasma hydrocortisone concentration 3.5 to 4.5 times base-line values at PIH 1, which was the time of maximal effect. The combined test concept for adrenal gland function is valid, convenient (three sample collections; 3-hour period), and allows testing of adrenal gland response to dexamethasone suppression and ACTH stimulation in a single trial. The following test procedure for dogs is recommended: (i) collect base-line plasma sample (0900 hours) followed by injection of dexamethasone (0.1 mg/kg, IM); (ii) collect second plasma sample 2 hours after dexamethasone (to evaluate suppression of plasma hydrocortisone concentration) followed by the injection of cosyntropin (0.5 U/kg, IV); and (iii) collect a third plasma sample 1 hour later to evaluate plasma hydrocortisone concentration after cosyntropin stimulation. PMID- 6255832 TI - Immunofluorescent studies on localization of secretory immunoglobulins in the intestines of turkeys recovered from turkey coronaviral enteritis. AB - The present study concerns the production of specific secretory antibodies in turkeys orally inoculated with turkey coronavirus (TCV). Tissue localization of secretory antibodies in the intestines of recovered birds 4 and 5 months later was demonstrated by immunofluorescence technique. Intestinal sections were stained by sandwich method, using concentrated TCV antigen and anti-TCV conjugate. It was suggested that local synthesis of antibody might be responsible for life-long immunity seen in these birds after recovery from infection. PMID- 6255833 TI - Feline respiratory tract disease in Louisiana. AB - An investigation of feline respiratory tract disease (FRD) was made involving 65 affected cats (group 1) and 65 control cats (group 2) matched for age, sex, and residence. Feline calicivirus strains (FCV), feline herpesvirus-1 (FHV-1), or both, were isolated from 59% of group 1 cats and from 7% of group 2 cats. Isolation of these viruses showed a significantly greater (P < 0.05) relative risk for group 1 cats. Virus isolations were three times more frequent from males than from females older than 1 year (both groups), but were equally distributed between males and females younger than 1 year. Bacteria and fungi had a secondary role in both FCV- and FHV-1 associated FRD. Intestinal infections of Ancylostoma spp, Dipylidium caninum, and Toxocara cati were diagnosed more frequently in group 1 cats than in control (group 2). Paragonimus kellicotti was diagnosed in 3 group 1 cats, Taenia taeniaeformis in 1 group 1 cat, Isospora rivolta in 1 group 1 cat, and Giardia cati in 1 control cat. The present study supports the current concept of a primary viral cause for development of FRD. PMID- 6255834 TI - Isolation of pseudorabies virus from trigeminal ganglia of a latently infected sow. AB - A 2-year-old sow with a relatively low virus-neutralization (VN) titer (1:8) against pseudorabies virus (PRV) was brought to the National Animal Disease Center for observation and study. The sow was kept in isolation for approximately 6 weeks, and repeated nasal and tonsillar swabs for virus isolation and blood samples for VN tests were obtained during this interval. At the end of 5 weeks' observation, the sow was injected IM with 200 mg of dexamethasone and was euthanatized 1 week later. Parts of the two trigeminal ganglia, tonsillar tissue, and nasal secretions were cultured in porcine kidney cells. The rest of the trigeminal ganglia was extracted with phenol and tested for presence of the PRV DNA genome by hybridization with tritiated complementary RNA. The PRV was isolated from the trigeminal ganglia only, and the PRV genome was demonstrated in the same tissue. This latently infected sow was a potential shedder of PRV. PMID- 6255835 TI - Detection of pseudorabies virus antibodies: time of appearance by two serotests. AB - This report describes a time-course comparison of detection of pseudorabies virus antibodies in experimentally infected swine by the virus-neutralization (VN) and indirect hemagglutination tests. Specific antibody titers were observed by the IHA test at 5 days after swine were inoculated, but not until 12 days by the VN test. The predominant immunoglobulin (Ig) class present in the serums of the swine at 5 and 7 days after inoculation was IgM, as determined by sulfhydryl reductions. The VN test lacked sensitivity to early Ig levels (IgM) in these experimentally infected swine, while the indirect hemagglutination test was highly sensitive to these same levels. On the basis of these results, it is possible that the VN test may read early infections as pseudorabies virus negative, due to the low presence of IgG in these samples. PMID- 6255836 TI - Crystalline inclusions in erythrocytes parasitized with Babesia equi following treatment of ponies with imidocarb. AB - Four splenectomized Welsh ponies were infected with Babesia equi. Two ponies were treated with imidocarb dipropionate, and two were not treated. By light microscopic examination, 1% to 2% of the parasitized erythrocytes of treated ponies contained crystalline inclusions. The crystals were rectangular, diamond, or burr shaped. They occupied most of the erythrocytic cytoplasm, and, as a result, the remainder of the pale staining cytoplasm was inconspicuous in Wright Giemsa-stained blood smears. The size and shape of intraerythrocytic inclusions varied when examined by electron microscopy, but in most instances they were either adhered to or were located close to the parasite. The sides of crystals were either smooth or serrated, and corners were either sharp or notched. Fractures or faults were common in large crystals. Parasitized erythrocytes of nontreated ponies and nonparasitized erythrocytes of treated ponies did not contain crystals. Four hemoglobulin types were identified in five noninfected, nontreated Welsh ponies from the same herd. PMID- 6255838 TI - An age-related coagulation disorder associated with experimental infection with infectious bursal disease virus. AB - Specific-pathogen-free White Leghorn chickens were inoculated with a field strain of infectious bursal disease virus. One group (A) was inoculated at 17 days after the chicks were hatched, and the other groups (C and E) were inoculated at posthatch day 42. Blood samples were obtained for determination of clotting times (whole blood recalcification, prothrombin, and activated partial thromboplastin times), virus-neutralizing antibody, and total hemolytic complement. There were significant increases in clotting times for groups C and E at 3 and 5 days after they were inoculated. There were no significant increases in clotting times at 3 days after inoculation in the group A chickens (inoculated at 17 days after hatching). There were no significant decreases in total complement activity in any of these chickens (groups A, C, and E). This study indicates that the mortality and clinical symptoms observed in chickens experimentally infected with infectious bursal disease virus may be associated with a clotting abnormality because it was noted only in chickens that developed severe clinical disease (inoculated at 42 days after hatching) and was not noted in chickens that remained clinically normal (inoculated at 17 days). PMID- 6255837 TI - Immunofluorescence studies on the pathogenesis of hemagglutinating encephalomyelitis virus infection in pigs after oronasal inoculation. AB - Hemagglutinating encephalomyelitis virus (HEV; also designated vomiting and wasting disease virus) was inoculated oronasally in 14 colostrum-deprived pigs at the day of birth. Anorexia and vomition were seen after 4 days. Pigs were killed at different times after inoculation, and the results of the examination by immunofluorescent antibody technique revealed that the epithelial cells of nasal mucosa, tonsils, lungs, and small intestine served as sites of primary viral replication. After the local replication near the sites of entry, the virus spread via peripheral nervous system to the CNS. During the incubation period, viral antigens were detected in the trigeminal ganglion,the inferior vagal ganglion, the superior cervical ganglion, the intestinal nervous plexuses, the solar ganglion, and the dorsal root ganglia of the lower thoracic region. In the brain stem, the infection started in the trigeminal and vagal sensory nuclei and spread to other nuclei and to the rostral part of the brain stem. In later stages of the infection, viral spread into the cerebrum, cerebellum, and spinal cord was sometimes also observed. Viral replication in nervous plexuses of the stomach was not present during the incubation period, but was detected in all except 1 of the pigs that were ill when killed. The question whether the vomition is induced centrally by viral replication in the brain stem or is due to viral replication in peripheral nervous tissues remains unanswered. PMID- 6255839 TI - Adrenal gland function in dogs given methylprednisolone. AB - Serum cortisol (hydrocortisone) was measured by radioimmunoassay in dogs given methylprednisolone (MP) orally or methylprednisolone acetate (MPA) IM. The MP was given on a daily and on an alternate-day basis to different treatment groups and the MPA was administered weekly. Samples of blood were obtained twice a week over a 9-week treatment period for serum cortisol determination, and the adrenal gland response to ACTH was assessed on posttreatment days 1, 3, 5, and 7. Administration of MP on an alternate or daily basis caused a slight but significant (P < 0.05) depression in mean resting cortisol values over time. The MPA administration caused a severe depression of resting serum cortisol values. In response to ACTH, cortisol values invariably increased sharply in nontreated control dogs and in those dogs given MP on an alternate-day basis. Dogs given MP daily had a depressed response to ACTH. The MPA treatment resulted in adrenal cortices that were unresponsive to ACTH. Dogs given MPA, but not challenge exposed with ACTH, had markedly lowered cortisol values for at least 2 weeks after cessation of treatment. Consequently, a difference between daily- and alternate-day MP administration was detected after ACTH challenge exposure; MPA administration inhibited adrenal cortisol secretion for at least the duration of the experiment. PMID- 6255840 TI - Cytoplasmic blood plasma inclusions of canine hepatocytes demonstration by immunoperoxidase-labeling method. AB - Cytoplasmic inclusions in canine hepatocytes were scattered abundantly throughout hepatic lobules. They were mainly round, measured 3 microns to 20 microns in diameter, stained eosinophilic with hematoxylin and eosin stain, and were positive for diastase-resistant periodic acid-Schiff and phosphotungstic acid hematoxylin stains. Immunoperoxidase staining revealed that most of the inclusions were positive for such blood plasma components as albumin, immunoglobulins G, M, A, and transferrin. Ultrastructurally, the inclusions were granular, floccular, fibrillar, or homogeneous with a low or high electron density. Fibrin fibers and erythrocytes were occasionally recognized in the inclusions. These inclusions were considered to have derived from engulfment of blood elements into hepatocytes, probably as a result of increase of the intrasinusoidal blood pressure. PMID- 6255841 TI - Morphogenesis of vesiculation in foot-and-mouth disease. AB - The morphogenesis of vesiculation in cattle inoculated (aerosol expsoure) with foot-and-mouth disease virus was investigated by examining alternate, frozen sections of selected tissues stained by fluorescent antibody technique and with hematoxylin and eosin. Viremia preceded the development of lesions, and virus appeared to be transported to the epithelium via papillae. Lesions were initiated usually by the infection of single cells in the stratum spinosum adjacent to the papillae. Three types of lesions were observed. A vesicle developed mainly from the lysis of swollen, spherical cells and the release of intracellular fluid. The 2nd type of lesion was formed mainly by the accumulation of intercellular edema. The 3rd type was characterized by the absence of a vesicle due to seepage and loss of edema fluid and desiccation of the lesion. PMID- 6255842 TI - Sensitivity and specificity of needle biopsy in lung malignancy. AB - Ninety-five patients with pulmonary parenchymal lesions suggestive of malignancy underwent 103 combined puncture-aspiration biopsies using an 18-gauge Rotex biopsy needle. The over-all sensitivity of the procedure was 90%, and the specificity was 95%, as determined by pathologic and clinical outcome. Needle biopsy was diagnostic in 69 of 77 patients (90%) with malignancy. In 3 patients with a false-negative biopsy result, a second needle biopsy was diagnostic, increasing the yield to 94%. One false-negative biopsy result occurred in a patient with actinomycosis. In the 17 patients in whom no malignancy was found on percutaneous biopsy, subsequent surgical biopsy, culture of aspirate, or stability or disappearance of the lesion within a year or more confirmed the initial diagnosis of nonmalignant disease. Pneumothorax was the only significant complication, requiring tube drainage after 6 biopsies (5.8%). Our study confirms that needle puncture-aspiration is an extremely reliable technique in diagnosing lung malignancy and is adaptable to use in a community teaching hospital. PMID- 6255844 TI - Treatment of chronic mucocutaneous candidiasis with ketoconazole: a controlled clinical trial. AB - Twelve patients with chronic mucocutaneous candidiasis were assigned by random allocation to a 6-month course of treatment with ketoconazole or placebo in a double-blind trial. All six recipients of ketoconazole had remission of symptoms and virtually complete regression of mucosal, skin, and nail lesions, whereas only two of the six receiving placebo had even temporary mucosal clearing, and none had improvement of skin or nail disease. The clinical outcome in the ketoconazole-treated group was significantly more favorable (p = 0.001) than in the placebo-treated group. The six patients receiving placebo in the controlled trial were then treated with ketoconazole in an open trial, and all responded favorably. Hepatitis, probably drug induced, developed in one patient after 6 months of treatment but proved to be mild and reversible. Oral ketoconazole is an effective treatment for chronic mucocutaneous candidiasis. PMID- 6255843 TI - An evaluation of herpes simplex virus antigenic markers in the study of established and developing cervical neoplasia. AB - Previous reports from our laboratory have shown that antiserum to "pure" AG-e, a type-common HSV antigen, specifically stains atypical cervical cells in indirect immunofluorescence. These observations have been confirmed and extended. Antisera were prepared against the two protein components of pure AG-e, designated ICP 12 (M. W. = 140,000) and ICP 14 (M. W. = 130,000), and were purified to radiochemical homogeneity by SDS-acrylamide gel electrophoresis. The antisera reacted as well as antiserum to pure AG-e in immunofluorescence with HSV-2-(G) infected cells, and their reactivity was adsorbed with pelleted HSV-2 (G) virions. Unlike antiserum to pure AG-e, the antisera to ICP 12 and ICP 14 were nonreactive in immunodiffusion, and only antiserum to ICP 12 showed complement fixation with soluble viral antigenic mixtures. Antisera to pure AG-e, ICP 12 and ICP 14 specifically stained exfoliated cervical cells from patients with herpetic cervicitis and atypical cells from patients with atypia, carcinoma in situ (CIS) or invasive cancer. However, both the number of patients with a positive response and the number of staining atypical cells were greater with antiserum to pure AG e than with antisera to ICP 12 or ICP 14, suggesting that AG-e is a superior marker. Cells staining with antiserum to pure AG-e, individually identified, were classified as atypia (mild to marked), CIS or cancer. The ability of the antiserum to pure AG-e to identify atypical cervical cells was compared to cytopathologic screening in a blind study of 26 patients. A good correlation (80% to 93.8%) was observed, indicating that pure AG-e is a sensitive and specific marker for the identification of atypical cells. PMID- 6255845 TI - An immunofluorescence test to detect serum antibodies to Giardia lamblia. AB - We used an indirect immunofluorescence test with Giardia lamblia trophozoites as antigen to detect anti-G. lamblia antibodies in serum. Seventy-one patients and control subjects were studied in a blinded protocol. Titers in 29 of 30 patients with symptomatic giardiasis (1:16 to 1:1024) did not overlap titers in 19 healthy control subjects (1:2 to 1:4); titers in 15 patients with hookworm, Entamoeba histolytica, or intestinal bacterial overgrowth were 1:16 or less Absorption of giardiasis patients' sera with G. lamblia trophozoites but not with E. histolytica, Trichomonas vaginalis, or Escherichia coli reduced the titers to, or nearly to, control values. Titers in individual sera were 93.9% reproducible within a fourfold or less dilution. Our results indicate that G. lamblia, an intestinal parasite often regarded as noninvasive, induces a systemic antibody response. The indirect immunofluorescence test for anti-G. lamblia antibodies is specific and reproducible; it may be useful in epidemiologic and immunologic studies of giardiasis. PMID- 6255846 TI - Serum angiotensin-converting enzyme: elevations in diabetes mellitus. AB - Elevated levels of serum angiotensin-converting enzyme were detected in 24% of 265 patients with diabetes mellitus. The elevations correlated strongly with the presence of severe retinopathy. Diabetes mellitus must be considered when an assay of serum angiotensin-converting enzyme is used to confirm a diagnosis of sarcoidosis. PMID- 6255847 TI - Relapse of Candida parapsilosis endocarditis after long-term suppression with flucytosin: retreatment with valve replacement and ketoconazole. PMID- 6255849 TI - Treatment of arrhythmias by blocking slow current. PMID- 6255848 TI - Calcium channel blocking agents in the treatment of cardiovascular disorders. Part I: Basic and clinical electrophysiologic effects. AB - Calcium ions play an important role in the cardiovascular system. They are involved in electrophysiologic processes, link excitation to muscular contraction, control energy storage and utilization, and constrict vascular smooth muscle in coronary and systemic arteries. A new group of pharmacologic agents that block the passage of calcium ions across cell membranes has been developed. These agents act during the slow inward current of cellular depolarization. The most extensive clinical experience has been obtained with four of these agents: verapamil, nifedipine, perhexiline, and diltiazem. Verapamil, which has profound electrophysiologic effects on the slow inward current, is emerging as a valuable antiarrhythmic agent. Re-entrant supraventricular arrhythmias, such as paroxysmal supraventricular tachycardia, are particularly amenable to treatment with intravenous verapamil. Preliminary trials of long-term therapy with oral verapamil for control of atrial fibrillation, atrial flutter, and paroxysmal supraventricular tachycardia suggest that this agent is effective for therapy of these arrhythmias. PMID- 6255850 TI - Ketoconazole: a major innovation for treatment of fungal disease. PMID- 6255851 TI - "Calcium influx blockers" and vascular smooth muscle: do we really understand the mechanisms? PMID- 6255852 TI - [Cefotaxime in the treatment of genital gonorrhea]. PMID- 6255853 TI - Plasma cortisone in man: its determination, physiological variation, and significance. AB - In a method for the simultaneous determination of cortisone, cortisol, and corticosterone, the extracted steroids are separated using paper chromatography and assayed by competitive protein binding. Evidence of the reliability of the method, particularly with respect to the determination of cortisone, is presented. Only trivial changes in cortisone level were detected in response to exercise, surgery, and ACTH, even though marked changes in cortisol level were simultaneously recorded. It is suggested that the inertia in plasma cortisone level may be related to its lesser degree of binding to plasma proteins, relative to cortisol, which would permit more rapid hepatic uptake and possible accumulation of a large extravascular pool of cortisone. PMID- 6255854 TI - Rapid random-donor screening for the selection of viral antibody-containing blood donations. AB - We describe a 3 1/2 year trial in which we used immunofluorescence to detect and titrate antibody to six common viruses in normal healthy blood donors drawn at random from West and South East Scotland. The trial was designed to allow selection of blood donations rich in specific antiviral antibody for inclusion in the plasma pool which would, in turn, be used for the preparation of specific antiviral immunoglobulin. The results show the natural frequency of occurrence of antibody to different viruses in healthy adult blood donors. PMID- 6255855 TI - The differential diagnosis of the polycythemic states. AB - The clinical and laboratory characteristics that are essential for the differential diagnosis of the polycythemic states are reviewed. The various forms of polycythemia that present as increases in hemoglobin concentration or packed red cell volumes can often be distinguished on the basis of pathophysiology, predisposition to neoplasia, hematological and viral parameters, chromosomal patterns, and response to therapy. Polycythemia vera differs from secondary and relative polycythemic states in its basic pathophysiology and etiology. It appears to be a clonal disorder that is characterized by a generalized bone marrow panmyelosis. Although the primary event leading to this stem cell disorder is not known, recent studies suggest a possible etiology. Therapeutic regimens based on the parameters inherent in making a differential diagnosis of the polycythemic states are discussed. Prognosis for polycythemia vera also appears to be predicated by the choice of drugs used to treat the disease. The consequences of making the correct diagnosis and of choosing appropriate therapy in light of the differences in underlying pathophysiology and etiology of the polycythemic states are stressed. PMID- 6255857 TI - [Action of novobiocin on the capacity of Nocardia fructiferi var. ristomycini for ristomycin biosynthesis]. AB - The effect of novobiocin in concentrations of 0.05 and 0.2--0.3 microgram/ml on morphological variation of N. fructifer and its capacity for ristomycin production was studied. It was found that the number of colonies with the maximum activity increased under the effect of novobiocin used in a concentration of 0.05 microgram/ml. An increase in the level of novobiocin in the medium up to 0.2- 0.3. microgram/ml markedly increased the number of the colonies with low antibiotic productivity. PMID- 6255856 TI - The role of phospholipids in platelet function. AB - Platelet phospholipids undergo significant alterations during aggregation induced by thrombin or other agents. There is an early increase in phosphatidic acid, with a decrease in phosphatidyl inositol. De novo synthesis of most phospholipids from 14C-glycerol is decreased. Thrombin stimulates 32P-phosphate incorporation into di- and triphosphoinositides, suggesting increased phosphorylation of phosphatidyl inositol during aggregation. Arachidonic acid for prostaglandin synthesis is released from platelet phospholipids. Thrombin induced aggregation results in release of arachidonic acid primarily from phosphatidyl choline and phosphatidyl inositol. The availability of free arachidonic acid may be regulated by platelet phospholipase A2 activity. The latter activity is stimulated by thrombin, requires calcium ions, and is inhibited by agents which elevate cyclic adenosine monophosphate. Phospholipids are probably an essential component of the platelet surface lipoprotein procoagulant activity known as platelet factor 3. There is evidence that calcium ions may mediate binding between gamma carboxyglutamic acid residues on the amino terminal portion of prothrombin and negatively charged phosphate groups on phospholipid micelles. Binding of prothrombin to phospholipid on the platelet surface may orient the former such as to facilitate the prothrombinase activity of Factor Xa. Platelet phospholipids and platelet factor 3 activity are decreased in some congenital and myeloproliferative disorders. Increases in these factors may be associated with thrombotic and arterial occlusive disorders. PMID- 6255858 TI - [Changes in the membrane ATPase activity of erythrocytes and Candida guilliermondii under the action of roseofungin]. AB - Changes in the Mg-ATPase and Na, K-ATPase activity of the rat erythrocyte and Candida guilliermondii membranes under the effect of roseofungin were studied. The antibiotic was totally bound to the isolated plasmatic membranes of Candida guilliermondii, up to 3 micrograms of the antibiotic per 1 microgram of the yeast protein. The Mg-APTase activity of these membranes was slightly inhibited by the antibiotic. The activity of Na, K-ATPase was almost completely inhibited even at 0.04 mg of roseofungin per 1 mg of protein. Much higher concentrations of the antibiotic inhibited the Mg-ATPase and Na, K-ATPase activity of the erythrocyte membranes to a less extent. PMID- 6255859 TI - [Phenomenon of intestinal microfloral increase after stopping the use of poorly adsorbed antibiotics]. AB - The results of studying intestine microflora in conventional mice (CBA X C57 BL/F1) during enteral treatment and after discontinuation of low-adsorbing antibiotics (gentamicin, restomycin and nystatin) are presented. The average daily doses of the antibiotics were 2.4, 3 mg and 110000 units respectively. For determination of the intestine microflora composition various media were used. It was found that a 7-day exposure of the mice to the above antibiotic combination resulted in total decontamination of their intestine. After discontinuation of the antibiotic there was a marked increase in the number of Coli bacteria, i. e. 10(7) times higher than the initial level. The number of other microorganisms returned to normal without any significant increase. It was shown that when the normal Coli microflore of the mice contained equal numbers of lactose-positive and lactose-negative strains, the increase after discontinuation of the antibiotic was mainly due to the lactose-positive organisms. Reduction of the initial quantitative and qualitative composition of the Coli flora was observed 7 -8 days after discontinuation of the antibiotic. The analysis of the experimental and literature data demonstrated that the marked increase in the number of the Coli forms in the intestine microflora resulted from discontinuation of antibiotic. Its universal character, connection with antagonistic relations of some microorganisms, the role of exogenic contamination and means for its decreasing are discussed. PMID- 6255860 TI - Antiviral activity of antilipidemic compounds on herpes simplex virus type 1. AB - Two antilipidemic compounds, clofibrate and procetofene, inhibited the replication of herpes simplex virus type 1 (HSV-1) in African green monkey kidney cells. Clofibrate, at a concentration of 400 mumol/liter caused a 63% reduction (P < 0.001) in HSV-1 yield and at 100 mumol/liter caused a 62% reduction (P < 0.001) in plaque formation. Two stereoisomeric analogs of clofibric acid, (-)- and (+)-desmethyl clofibric acid, also caused a significant inhibition of HSV-1 replication. Procetofene at 5 mumol/liter caused a 56% reduction (P < 0.001) in HSV-1 plaques and at 10 mumol/liter caused a significant reduction (P < 0.001) in both viral yield (42 to 54%) and plaque formation (65%). Procetofene also inhibited the development of HSV-1 plaques. A concentration of 5 mumol/liter resulted in a 26% reduction (P < 0.001) in plaque diameter. Because of their nonspecific inhibitory effect on the uptake of cellular macromolecular precursors for nucleic acid and protein biosynthesis, these antilipidemic compounds may exert their antiviral activity by affecting one or more key metabolic host cell pathways. PMID- 6255861 TI - Relationship between metronidazole metabolism and bactericidal activity. AB - It has been suggested that the microbicidal effect of metronidazole is mediated by an intermediate in nitro group reduction. We have found that the addition of Escherichia coli enhances the lethal effect of metronidazole on Bacillus fragilis and suggest that this intermediate may form in one bacteria and kill another. Because acetamide forms during the reduction of metronidazole, we examined the possibility that the same partially reduced intermediate in metronidazole reduction may be both an intermediate in the formation of acetamide and the ultimate reactive form of metronidazole which is responsible for its bactericidal action. Thus, we determined the relationship between bacterial survival and the formation of acetamide when cultures of B. fragilis, Clostridium perfringens, and E. coli were incubated anaerobically in the presence of metronidazole. We found that the log of the early bacterial survival was proportional to the formation of acetamide. The rate of loss of metronidazole was not dependent on the concentration of bacteria in the medium, suggesting that any proposed intermediate formed at a rate which was proportional only to the concentration of metronidazole. PMID- 6255862 TI - Synergistic activity of piperacillin in combination with beta-lactamase inhibitors. AB - Clavulanic acid and a penicillanic acid sulfone, when combined individually with piperacillin, synergistically inhibited various Enterobacteriaceae, Staphylococcus aureus, and Bacteroides fragilis. Clavulanic acid and piperacillin synergistically inhibited 91 of 170 (55%) isolates tested. Synergy was most often found against piperacillin-resistant bacteria: 65 of 69 isolates (94%). Although the penicillanic acid sulfone acted synergistically with piperacillin, inhibiting 62 of 170 strains (33%), the concentration of clavulanic acid required for synergy generally was less than that of penicillanic acid sulfone. Combination of piperacillin and cefotaxime, an inhibitor of type 1 beta-lactamases, rarely was synergistic and was antagonistic for several species. The combination of piperacillin with potent beta-lactamase inhibitors made piperacillin active against those isolates of Escherichia coli and Klebsiella and Bacteroides species, as well as selected other species, that are resistant to piperacillin by virtue of their production of beta-lactamases. PMID- 6255864 TI - Comparative in vitro activity of moxalactam, cefotaxime, cefoperazone, piperacillin, and aminoglycosides against gram-negative bacilli. AB - The in vitro activities of four new beta-lactam antimicrobial agents (moxalactam, cefotaxime, cefoperazone, and piperacillin) and the aminoglycosides against 744 recent clinical isolates of facultative gram-negative bacilli were compared simultaneously by the agar dilution method. The major in vitro difference of these newer beta-lactam compounds appeared to be their antipseudomonal activity; cefoperazone was the most active, whereas cefotaxime had the least potency. The aminoglycosides, however, had the most effective in vitro activity on a weight basis against Pseudomonas aeruginosa. PMID- 6255863 TI - Erythro-9-(2-hydroxy-3-nonyl) Adenine alone and in combination with 9-beta-D arabinofuranosyladenine in treatment of systemic herpesvirus infections in mice. AB - Although the antiviral activity of erythro-9-(2-hydroxy-3-nonyl)adenine, a potent adenosine deaminase inhibitor, against herpes simplex virus type 1 in cell culture was readily confirmed, the compound was found to be totally ineffective in the treatment of experimentally induced systemic herpes simplex virus type 1 infections in Swiss mice. Data were obtained, however, which clearly indicated that the antiviral potency of 9-beta-D-arabinofuranosyladenine in vivo could be enhanced by the co-administration of low, nontoxic doses of erythro-9-(2-hydroxy 3-nonyl)adenine. PMID- 6255865 TI - Effect of beta-lactamase and salt on mecillinam susceptibility of enterobacterial strains. AB - Out of 15 selected enterobacterial strains resistant to ampicillin, 12 were able to transfer resistance to mecillinam to Escherichia coli K-12. This resistance to mecillinam was found to be coupled to the presence of beta-lactamase. One strain contained a beta-lactamase characterized as a class IV beta-lactamase, whereas the other 14 strains possessed a class III (TEM-like) beta-lactamase. The specific activity of the class IV beta-lactamase against mecillinam was 55%, and those of the class III beta-lactamase sensitivity of mecillinam, the minimal inhibitory concentrations were lower than might be expected. However, after enzymatic hydrolysis of mecillinam, no antibacterial activity was found. At increasing salt or buffer concentrations the minimal inhibitory concentrations of mecillinam increase to a varying extent for all strains, independently of beta lactamase production. This study indicates that the increase in minimal inhibitory concentration is dependent on the salt concentration. The study also shows that this increase is not due to salt-mediated hydrolysis or to stimulation either of beta-lactamase activity or of beta-lactamase production. To explain the difference between ampicillin and mecillnam resistance in the beta-lactamase positive strains, a hypothetical model is presented and discussed. PMID- 6255866 TI - Plasmids in Corynebacterium diphtheriae and diphtheroids mediating erythromycin resistance. AB - Plasmids were isolated from erythromycin-resistant Corynebacterium diphtheriae and skin coryneforms. Six erythromycin-resistant C. diphtheriae strains, isolated from cutaneous lesions, all contained a 9.5-megadalton (Mdal) plasmid. Loss of resistance was associated with the deletion of a 1-Mdal segment from the plasmid or, less frequently, with loss of the plasmid. Two erythromycin-resistant diphtheroids were isolated from similar skin lesions. One contained a 38-Mdal plasmid that was lost in the conversion to erythromycin susceptibiliy. The other diphtheroid contained a 30- and a 14-Mdal plasmid. Erythromycin-susceptible derivatives of this strain were not recovered. Restriction enzyme analysis indicated that the 9.5-Mdal plasmids in the C. diphtheriae strains are very similar, if not identical, and that each of the deleted plasmids has lost the same 1-Mdal segment. However, the restriction patterns of the plasmids in the two diphtheroids are not closely related to each other nor to the plasmids in the C. diphtheriae strains. PMID- 6255868 TI - [Virus survival in freeze-dried vaccines prepared in bovine lymph]. PMID- 6255867 TI - Persistence of the pBR 322 plasmid in Escherichia coli K 12 grown in chemostat cultures. AB - Populations of a Escherichia coli K 12 strain, containing the vector plasmid pBR 322, were grown in chemostat culture under glucose- and phosphate-limited conditions. Resistance to tetracycline and ampicillin were lost after prolonged cultivation, resulting in the production of apparent plasmid-free populations which were more competitive than the original population. This competitiveness between plasmid-free and plasmid-containing populations was greatest in environments where the nutrient restriction was severe. Also during sequential subcultivation in batch cultures loss of plasmid was observed. PMID- 6255869 TI - Effect of melittin-induced membrane alterations on rat heart adenylate cyclase activity. PMID- 6255870 TI - Glucocorticoid-induced changes in poly(ADP-ribose) synthetase activity from chick embryo liver. PMID- 6255871 TI - Enzymic memory studies with nucleoside-5'-diphosphate kinase. PMID- 6255872 TI - An imidoester spin probe of membrane protein interactions: application to cytochrome c. PMID- 6255873 TI - Orientation and reactivity of cytochrome aa3 heme groups in proteoliposomes. PMID- 6255874 TI - The metabolism of taurine to isethionate. PMID- 6255875 TI - Studies of the mechanism of action and regulation of cAMP-dependent protein kinase. PMID- 6255876 TI - The carbon dioxide hydration activity of brush-border carbonic anhydrase from the dog kidney. PMID- 6255877 TI - Effect of theophylline in atopic dermatitis: a double-blind cross-over study. PMID- 6255878 TI - The effects of long-term local PUVA treatment on collagen metabolism in human skin. AB - The effect of photochemotherapy on skin collagen metabolism was investigated in 57 patients with psoriasis. Twenty-eight patients were treated with trioxsalen baths and UVA irradiation, nine with ditranol and UVB irradiation, and 20 untreated psoriasis patients served as controls. No significant changes were found between the treated groups and the control group in urinary hydroxyproline excretion, skin hydroxyproline content, or in the activities of two enzymes catalyzing collagen biosynthesis, prolyl hydroxylase, and galactosylhydroxylysyl glucosyltransferase in the skin. When the same parameters were compared with the cumulative doses of UVA irradiation, skin prolyl hydroxylase activity slightly decreased with increasing UVA doses, whereas no changes were found in skin hydroxyproline content or galactosyl-hydroxylysyl glucosyltransferase activity. It was concluded that long-term local PUVA therapy does not significantly alter collagen metabolism in the skin. PMID- 6255879 TI - [Malignant evolution of a mediastinal chemodectoma. An ultrastructural study (author's transl)]. PMID- 6255880 TI - Inhibition of adrenergic neurotransmission in canine saphenous veins and tibial arteries by streptokinase. PMID- 6255881 TI - Delta-9-tetrahydrocannabinol on isolated human bronchioles. AB - Experiments were conducted to investigate the bronchodilating action of delta-9 tetrahydrocannabinol (THC) using normal human lung tissue obtained post mortem. Isolated rings of human bronchioles contracted to histamine, carbachol, and prostaglandin F(2a)(PGF(2a)) and relaxed to isoproterenol. THC (5 X 10(-4)M) did not alter the responses of the bronchial rings to histamine, whereas methapyrilene (10(-6)M) antagonized these responses. Atropine (2 X 10(-6)M) had a highly significant effect on the responses of the bronchioles to carbachol: there was also a significant effect of THC (5 X 10(-4)M), but to a much lesser extent than atropine. Propranolol (10(-6)M) pretreatment significantly antagonized the relaxant responses of the bronchioles to isoproternol: THC antagonized these responses to a smaller degree. Incubation with THC did not cause relaxation of resting tissues or tissues in which a spasm had been induced. These data suggest that THC does not have significant direct effects in human bronchial smooth muscle and that bronchoactivity observed in vivo is likely to be of a nondirect or central origin. PMID- 6255882 TI - Di- and trihydroxy analogs of chlorpromazine influence the central activity of adenylate cyclase and cyclic AMP phosphodiesterase. AB - We previously demonstrated that chlorpromazine (CPZ), 7,8 diOH-CPZ and 3,7,8 triOH-CPZ were potent inhibitors of central adenylate cyclase systems. The present studies were thus designed to observe whether further substitutions of dihydroxy groups on the CPZ molecule would influence adenylate cyclase in broken cell preparations of the rat frontal cortex. The inhibition of adenylate cyclase by 7,8 diOH-CPZ was further found to be noncompetitive with respect to ATP concentration. Raising the Ca++ concentration obliterated adenylate cyclase activation by either dopamine or 5'-guanylylimidodiphosphate (Gpp(NH)p) alone or in combination, while inhibition by 7,8 diOH-CPZ was overcome. The enzyme inhibition by 7,8 diOH-CPZ was not influenced, however, by increasing Mg++ concentration. Incubation of rat cortical homogenates with CPZ, 3,7,8 triOH-CPZ or 6,9 diOH-CPZ inhibited stimulation of adenylate cyclase activity while either 3,7- or 3,8 diOH-CPZ resulted in an enhancement of enzyme activity. In further study, using the high speed cortical supernatant, the high Km form of cyclic AMP phosphodiesterase and its activation by the Ca++-dependent, heat stable regulator protein were inhibited by CPZ, 6,9 dioxo-, 7,8 dioxo-, 3,7diOH-, 3,8 diOH-, 6,9 diOH-, 7,9 diOH- and 7,8 diOH-CPZs, but not by 3,7,8 triOH-CZP. The high affinity low Km form of the enzyme was inhibited to a considerably lesser extent by these analogs. The studies reveal rather diverse and complicated actions of CPZ and its putative metabolites on central enzyme systems. PMID- 6255883 TI - Amebiasis. A persistent problem. PMID- 6255885 TI - [Hereditary anomalies of purine metabolism. Current biochemical aspects]. PMID- 6255884 TI - The effect of nisin on murein synthesis. AB - Nisin inhibits murein synthesis with concomitant accumulation of undecaprenyl pyrophospho-MurHAc(pentapeptide) (lipid intermediate I). This inhibition is caused by the formation of a complex between the antibiotic and lipid intermediate I. Undecaprenyl-pyrophospho-MurNAc(pentapeptide)-GlcNAc (lipid intermediate II) also forms a complex with nisin. However, when murein synthesis is inhibited by nisin, this latter complex is not formed since lipid intermediate II is not longer synthesized. PMID- 6255886 TI - [Seroepidemiology of herpesvirus hominis and cytomegalovirus infections in the first 4 years of life (author's transl)]. AB - Two hundred children and their mothers were examined when they were 10 months, 2 years and 4 years of age. Anti-cytomegalovirus, anti-Herpesvirus hominis and anti rubella virus antibodies were titered. The evolution of antibody titers showed that primary infections with cytomegalovirus and Herpesvirus are especially frequent during the first months of life, and that mothers are the principal source of infection. In the group studied, it appeared that country of origin of the parents was the most important socio-economic factor influencing the frequency of infections in children, based upon the large variations of the serum positivity in mothers. PMID- 6255887 TI - [Plasma dehydroepiandrosterone sulfate (DHAS) in paediatric endocrinology (author's transl)]. AB - The normal values of plasma DHAS were determined by measuring the levels in 637 normal subjects whose ages ranged from birth to adulthood. The changes induced by adrenal stimulation and suppression, and by testicular stimulation tests were studied. Knowledge of the normal values and the changes with age is essential for the interpretation of the results in children with endocrine disorders. Normal DHAS levels were found in cases of precocious puberty. High levels were found in pseudo-precocious puberty and in premature pubarche. Low levels were detected in primary or secondary adrenal insufficiency and in delayed adrenal puberty. PMID- 6255888 TI - Clonidine ameliorates Gilles de la Tourette syndrome. AB - Gilles de la Tourette syndrome (TS) is a severe, familial neuropsychiatric disorder of childhood onset that is characterized by multiform motor, phonic, behavioral, and psychological symptoms. Clonidine hydrochloride, a centrally active alpha-adrenergic agonist, was observed to ameliorate the disorder in the majority of 25 patients who could not tolerate or did not benefit from treatment with haloperidol. Clonidine had a gradual onset of action. Compulsive behavior, frustration intolerance, speech difficulties, behavioral blocking, attentional problems, and tics were responsive to treatment. The noradrenergic system may be involved, primarily or secondarily, in the expression of the genetic predisposition to TS. These observations will require testing by suitably controlled efficacy studies. PMID- 6255890 TI - Double infection of BALB/c mice with Rauscher murine leukemia and Herpes simplex virus type 2. AB - When BALB/c mice were first infected with Rauscher murine leukemia virus (MuLV-R) and then superinfected with Herpes simplex virus type 2 (HSV-2) the inhibition of the evolution of splenomegaly was observed. The effect did not depend on the route of HSV-2 administration. Experiments in which potent anti-interferon serum was administered to double infected mice suggested that the antagonism between MuLV-R and HSV-2 was not mediated by endogenous interferon, HSV-2 was found to replicate in the LPS stimulated spleen cells which are also target cells for MuLV R; this suggested that the intrinsic interference between both viruses could take place. Mice with Rauscher virus induced disease were found to be more susceptible to infection with Herpesviruses than normal mice. PMID- 6255889 TI - The regulation of the immune response to polyvinylpyrollidone: antigen induced changes in prostaglandin and cyclic nucleotide levels. AB - Having previously established, that prostaglandins play a role in the regulation of the immune response to polyvinyl pyrollidone, a T-independent antigen, further investigations of the role of prostaglandins and cyclic nucleotides in the control of the immune response to polyvinyl pyrollidone were initiated. Strongly immunogenic (PVP 360,000) and weakly immunogenic (PVP 10,000) molecular sizes of polyvinyl pyrollidone were examined for their effects on splenic PGF2 alpha, PGE and cyclic nucleotide levels. The results show, that PVP 360,000 induces marked changes in PGF2 levels. There is an early marked depression at 2 hours after injection followed by an increase which peaks at 2 hour. At subsequent time intervals (9-10, 13-14 and 16-18 hour) high values were observed, especially in the latter case. cAMP levels undergo significant fluctuations, exhibiting very big rise at 12 and 13 hour post-immunization, cGMP levels are elevated at 2 hour declining thereafter. PGE level in C57Bl mice exhibits very substantial increase at 4-6 hour after immunization, in athymic mice, however, the increase was not significant and was preceded by a profound drop in PGE concentration. PGE level in the splenocytes from athymic mice shows a constant increase till 4 hour after PVP addition, followed by a little decrease at 6-7 hour. cAMP concentration in athymic mice exhibits a drop at 3-4 hour after immunization, followed by an increase at 5-6 hour post-immunization. Indomethacin, an inhibitor of prostaglandin synthetase, blocks the changes in PGF2 and cGMP level but has little effect on cAMP. In contrast, the weakly immunogenic form PVP 10,000 induces a large bimodal increase in cAMP levels peaking at 2 hour and again increasing between 6-8 hour; cGMP levels also rise, but more slowly. The increase in cAMP is blocked by indomethacin even though no comparable increases in PGF2 levels are observed. The changes induced by PVP 10,000 appear to be dependent on T cells since comparable changes are not observed in athymic mice. Although PVP 10,000 is non-immunogenic in normal mice or whole spleen cultures, it is immunogenic in athymic mice and purified B cell cultures. This difference has been traced to an apparent difference in the activation of T cells vs. B cells by PVP 10,000. Lastly, although inhibition of PG synthesis results in an enhancement of the immune response to PVP 360,000, no such enhancement is observed with PVP 10,000. The relevance of prostaglandin and cyclic nucleotide changes to the development of the immune response is discussed. PMID- 6255892 TI - [Solitary carcinoma metastasis in Paget's disease. Distinction from sarcomatous changes (author's transl)]. AB - This report concerns a 77 years old woman with a solitary metastasis of a bronchiogenic carcinoma to the humerus, which had been involved by previously diagnosed polyostotic M. Paget (ostitis deformans). The distinction from sarcomatous changes in Paget's disease is discussed. PMID- 6255891 TI - The influence of prostaglandins on non-specifically stimulated human lymphocytes. AB - The influence of E2 and PGF2 alpha-prostaglandins on the level of cAMP in non stimulated and stimulated by lectins lymphocytes has been studied. PGE2 increased clearly the level of intracellular cAMP but did not increase the number of blastic cells in the culture. PGF2 alpha did not change any of these factors. Prostaglandins (E2 and F2 alpha) did not influence the level of cAMP in lymphocytes affected previously by lectins (PHA and Con A), except Con A+PGF2 alpha scheme. PGE2 (and partly PGF2 alpha and lectins are supposed to act competitively in relation to the same receptor of lymphocyte cells. PMID- 6255893 TI - Malignant histiocytoma in talus: diagnostic problems. AB - A malignant histiocytoma of the left talus is described. The patient was introduced to our hospital because of an infected recidivation of a partly exstirpated tumor. It is classified as a metastasis of a malignant melanoma. The final histologic diagnosis could be proved by the original slides. The exarticulation of the knee was followed by chemotherapy. PMID- 6255894 TI - Granular cell myoblastoma of the hands. Report of a child with multiple tumors. AB - A child with 2 granular cell myoblastomas, one in the right hand and the other in the left third finger, both treated with local resection, are reported. A short review of this uncommon benign tumor, found in many different anatomical locations, is given. PMID- 6255895 TI - Selective inhibition of herpes simplex virus glycoprotein synthesis by a benz amidinohydrazone derivative. AB - 1H-benz[f]indene-1.3(2H)dione-bis-amidinohydrazone (benzhydrazone) inhibited incorporation of 14C-glucosamine, 14C-fucose and 14C-mannose into glycoproteins of HEp-2 cells infected with various strains of herpes simplex virus 1 (HSV-1) and impaired RNA and protein synthesis to a low extent. These biochemical effects are very similar to those induced by glycosylation inhibitors such as tunicamycin, D-glucosamine and 2-deoxy-D-glucose. In contrast to these inhibitors, benzhydrazone reduced HSV glycoprotein synthesis selectively since it did not significantly modify i) the saccharide uptake into glycoproteins of uninfected and of Sindbis virus-infected cells, ii) viral growth and cell fusion in paramyxovirus-infected cells, two activities which depend on viral glycoprotein synthesis. Benzhydrazone had only minor effects on the overall metabolism of uninfected cells, since it did not alter cell growth rate, and amino acid, uridine, and hexose incorporations were about 80% those of untreated cells. PMID- 6255896 TI - Immunogenicity of subviral herpes simplex virus type 1 preparation: protection of mice against intradermal challenge with type 1 and type 2 viruses. AB - An intradermal assay system for herpes simplex virus in the infected pinna (external ear) of mice was utilized for examining the immunogenicity of an experimental subviral herpes simplex type 1 virus vaccine. The administration of one dose of vaccine with adjuvant did not prevent the appearance of erythema; however, it markedly reduced the severity skin lesions induced by either type 1 or type 2 virus. In addition, neurological complications frequently seen in control mice were never observed in immunized animals. In subsequent experiments the virus content in the pinna tissues of immunized and control animals was determined at different intervals after infection. The results suggest that the immunization had resulted in an acceleration of the clearance of infectious virus from the tissues. PMID- 6255898 TI - Vesicular stomatitis virus pseudotypes produced by cells abortively infected or transformed by human cytomegalovirus. AB - Pseudotypes of vesicular stomatitis virus (VSV) and human cytomegalovirus (HCMV) were produced by normal hamster cells abortively infected with HCMV and superinfected by VSV at a certain stage of abortive HCMV infection. Hamster cells transformed in vitro by HCMV (87-TRH-5 and CX-90-3B cells) also produce VSV (HCMV) pseudotypes after infection of the cells by VSV, but the same cells after passage in vivo (TSC-1, TSC-2 cells) do not. PMID- 6255897 TI - Secondary structures of influenza and Sendai Virus RNAs. AB - The secondary structures of influenza and Sendai virus RNAs were investigated by thermal denaturation, circular dichroism and proflavine binding methods. In 0.1 M NaCl about 60% of the bases of both RNAs were involved in secondary structure. The melting temperatures (Tm) of both viral RNAs were linear functions of the logarithm of the sodium ion concentration in solution, but under all ionic conditions the melting temperatures of Sendai virus RNA were higher than those of influenza virus RNA. At all ionic strengths the melting range of Sendai virus RNA was less than influenza virus RNA, indicating that the helical regions in Sendai virus RNA were longer than those in influenza virus RNA. Although Sendai virus RNA had a higher thermal stability than influenza virus RNA, hyperchromicity and circular dichroism data showed that Sendai virus RNA had less G+C content (34%) within the double stranded regions than influenza virus RNA (48%). The binding isotherms of Sendai and influenza virus RNA-proflavine complexes were studied at different ionic strengths. The number of binding sites of proflavine with influenza virus RNA were significantly lower than those with Sendai virus RNA. These results demonstrate the essential difference between the secondary and tertiary structures of the RNAs under study. PMID- 6255899 TI - Protection of chickens against challenge with virulent influenza A viruses of Hav5 subtype conferred by prior infection with influenza A viruses of Hsw1 subtype. AB - Prior infection of six-week-old chickens with influenza A viruses of Hsw1 haemagglutinin subtype and irrelevant neuraminidase subtypes reduced the deaths and sickness in groups of those birds challenged with A/tern/s. Africa/61 (Hav5Nav2/3) and A/chicken/Scotland/59 (Hav5N1). PMID- 6255900 TI - Isolation of a recombinant influenza virus (Hsw 1 N2) from swine in Japan. AB - Outbreaks of swine influenza were first observed in Japan in 1978. A number of influenza viruses were isolated from diseased swine. Almost all viruses isolated were swine influenza virus (Hsw 1 N1) but two viruses isolated from the nasal swabs of swine showing clinical signs of influenza in the Kanagawa prefecture were characterized antigenically as Hsw 1 N2. Analysis of swine sera showed that influenza virus Hsw 1 N2 was epidemic in the farm from which the virus had been isolated. The new virus (Hsw 1 N2) seems to have been produced by recombination between swine influenza virus (Hsw 1 N1) and Hong Kong influenza virus (H3N2). PMID- 6255901 TI - Cytotoxic antibody in cattle and sheep exposed to bovine leukemia virus. AB - Sera from bovine leukemia virus-infected cattle and sheep lysed fetal lamb kidney cells in the presence of rabbit complement. This cytolytic activity was removed completely from the sera by absorption with bovine leukemia virus (BLV). Antiserum against surface glycoprotein antigens of BLV contained cytolytic antibody but antiserum against the internal protein p24 did not. The complement dependent antibody cytotoxicity test employing the trypan-blue dye exclusion method appeared to be suitable for routine diagnosis of BLV infection. PMID- 6255903 TI - Growth characteristics of two strains of bovine virus diarrhoea virus. AB - The replication cycles of a cytopathogenic and a non-cytopathogenic strain of bovine virus diarrhoea virus (BVDV) were similar in kinetics and the tendency of cell-free infectivity to exceed the titre of cell-associated, but differed in virus yield per cell. Actinomycin D enhanced the yield of the non-cytopathogenic strain and depressed that of the cytopathogenic strain. PMID- 6255904 TI - [Extrarenal variant of an embryonal nephroma]. AB - A rare variant of embryonal nephroma in a man of 18 is described. Epithelial and mesodermal components were markedly distinctive in the tumour. The epithelial part of the tumour was represented by tubules resembling renal tubules, and glomerulo-like structures, and the mesodermal part consisted of cross-striated muscles, edematous connective tissue and osteoid substance. PMID- 6255902 TI - Infection of rhesus monkeys and chimpanzees with Epstein-Barr virus. AB - Seventy-two nonhuman primates were entered into a long-term study to evaluate the pathogenicity of Epstein-Barr virus (EBV). Infectious virus was inoculated into 42 rhesus monkeys, 4 chimpanzees and 1 cynomolgus monkey. Immunostimulation or immunosuppression was attempted in 34 of these animals to enhance the oncogenic potential of the virus. Eleven inoculated animals were followed for more than 3 years and two were observed for 8 years. No tumors were observed in any of the animals; however, serological evaluation of the 47 inoculated primates and 25 matched controls indicated that at least 14 rhesus monkeys and the cynomolgus monkey were successfully infected with EBV. The potential use of rhesus monkeys as a model for EBV-induced disease in humans is discussed. PMID- 6255905 TI - [Clinical morphological characteristics of tumors in children]. AB - The clinicomorphological analysis of 60 cases of testicular tumours in children based on the WHO International Histological Classification of testicular tumours (1977) showed the most frequent kind of germinogenic group neoplasias to be tumours of the yolk sac or embryonal carcinoma of the infantile type (24 out of 60) followed in frequency by mature teratomas (7) and teratocarcinomas (8). Among the tumours of the tissues surrounding the testicle, embryonal rhabdomyosarcomas are most prevalent (10). Tumours of testes occur mostly in children under 3 years. Positive remote results of the composite treatment were obtained in 65% observations. PMID- 6255906 TI - [Lung cancer according to autopsy data from the Pathologicoanatomical Institute in Hradec Kralove (Czechoslovak SSR) for 1978]. AB - The analysis of autopsy materials for the year revealed 75 cases of pulmonary carcinoma, predominantly in men (10.9:1). Particular attention was paid to the association of pulmonary carcinoma with the duration and intensity of cigarette smoking by the patients. The results of the comparison of these data suggest that the majority of men (94.1%) dying of pulmonary carcinoma had been inveterate smokers who had smoked on an average 388,000 cigarettes during their lifetime. A high per cent of pulmonary carcinoma among other fatal diseases and a significant number of cases of this disease unrecognized before death were noted. PMID- 6255907 TI - [Histocytospectrophotometric characteristics of lung cancer]. AB - The paper presents the results of quantitative changes in the activity of some most important oxidative-reductive enzymes in lung carcinoma cells. The histo- and cytospectrophotometric studies were carried out on the operation material removed from 32 patient with lung carcinoma including 12 cases of squamous cell carcinoma, 12 cases of adenocarcinoma, 4 cases of undifferentiated large cell and 4 cases of undifferentiated small cell carcinoma. Statistically significant increases in the activity of G-6-PDH, NADP-D and LDH were observed in a decreasing degree of tumour differentiation with a simultaneous relative decrease in the activity of SDH, MDH NAD-D and alpha-GPDH. When the activity of oxidoreductases was compared in tumours having the structure of squamous cell carcinoma and adenocarcinoma, a higher activity of LDH, SDH and alpha-GPDH in squamous cell carcinoma and high activity of G-6-PDH and NADP-D in adenocarcinoma were observed. Statistically significant differences in the activity of carbohydrate metabolism enzymes in small cell carcinoma and other histological forms of lung cancer were found: a significant increase in G-6-PDH and LDH and relative decline in the activity of SDH and alpha-GPDH. In all the examined histological forms of lung cancer there was a complete agreement in the results of histo- and cytospectrophotometric examinations of the activity of the main oxidative-reductive enzymes. PMID- 6255908 TI - [Comparative histo- and cytospectrophotometric study of the DNA content in the nuclei of lung cancer cells]. AB - Histo- and cytospectrophotometric examinations of the lung carcinoma (26 observations, operation material) established that such features as hetero- and polyploidy, a considerable increase in the average content of DNA and "index of DNA accumulation" progressed as long as the degree of tumour differentiation decreased. Differences between poorly differentiated forms of squamous cell carcinoma and adenocarcinoma were found (the latter had more octoploid and other polyploid cells, higher values of the "index of DNA accumulation" and a significantly higher average DNA content in the nuclei than in squamous cell carcinoma) as well as between small- and large-cell variants of undifferentiated cancer (the latter had more octoploid and other polyploid cells, higher "index of DNA accumulation" and significantly higher average DNA content in the nuclei than in undifferentiated small-cell carcinoma). The cytospectrophotometric method for DNA determination may be used as an auxilliary test for the determination of the histological form, the degree of differentiation of lung carcinoma prognosis, and choice of the method of treatment. PMID- 6255909 TI - Herpes simplex virus encephalitis: new diagnostic and clinical features and results of therapy. AB - Six patients with herpes simplex virus (HSV) encephalitis underwent diagnostic and clinical evaluation. The HSV or its antigenic material was found in three brain biopsy specimens. In the remaining three cases, the diagnosis was supported by detection of HSV antibodies in the CSF. Cell count and total protein concentration in the CSF reached a maximum level at three weeks and two months, respectively. The IgG index and HSV antibody level in the CSF often remained constant after reaching maximal values. In three patients, a transient low serum sodium level was observed. Characteristic EEG changes were present five to 11 days after the onset of symptoms. Computerized tomographic scanning revealed a temporal low-density lesion. Three patients became deeply comatose and had respiratory failure. The patient without vidarabine therapy and one of the five patients treated with vidarabine died. PMID- 6255910 TI - Baclofen in trigeminal neuralgia: its effect on the spinal trigeminal nucleus: a pilot study. AB - Experiments with cats showed that baclofen resembles carbamazepine and phenytoin sodium in its ability to depress excitatory synaptic transmission in the spinal trigeminal nucleus. Baclofen was, therefore, given to 14 patients with refractory trigeminal neuralgia. Ten patients were relieved of the paroxysms of tic douloureux while taking 60 to 80 mg/day of baclofen. A reduction in the dosage of baclofen in six of these patients resulted in a recurrence of painful paroxysms in five patients. Seven patients have been pain-free or almost pain-free on a regimen of baclofen for four to 12 months. Our results suggest that baclofen may be a useful drug in the treatment of trigeminal neuralgia and that our experimental model may successfully predict the efficacy of a drug in the treatment of this condition. PMID- 6255911 TI - Guillain-Barre-like Polyneuropathy after renal transplant: possible association with cytomegalovirus infection. PMID- 6255912 TI - Cylindroma causing Garcin's syndrome. PMID- 6255913 TI - Aseptic meningitis by echovirus associated with herpes progenitalis. PMID- 6255914 TI - Cell-protective effect of human saliva specific for herpes simplex virus. PMID- 6255915 TI - Inhibitors of collagenolytic enzymes synthesized by fibroblasts and epithelial cells from porcine and macaque periodontal tissues. PMID- 6255916 TI - Immunohistochemical evidence that electric currents increase periosteal cell cyclic nucleotide levels in feline alveolar bone in vivo. PMID- 6255917 TI - Electron-spin resonance study of the effects of carbonate substitution in synthetic apatites and apatites from human teeth. PMID- 6255918 TI - Effect of cortisol on medial edge epithelium of organ-cultured single palatal shelves from steroid-susceptible mouse strains. PMID- 6255919 TI - Towards prediction and surveillance of Murray Valley encephalitis activity in Australia. AB - Current practices for early warning of activity of Murray Valley encephalitis and other medically-important arboviruses are reviewed with view to improvement. Data from previous papers on Culex annulirostris populations, environmental factors and virus infection rates were reanalysed and the results considered as a basis for prediction and surveillance. This goal will only be achieved with improved national cooperation, a better epidemiological understanding and greater knowledge of the bionomics of the major vector, Culex annulirostris. The improved monitoring system will utilize meteorological, serological and entomological criteria. PMID- 6255920 TI - Non-chromaffin, non-functioning retroperitoneal paragangliomas: a report of three additional cases with a review of the literature. AB - A review of the literature has revealed only 24 cases of retroperitoneal non functional paraganglioma recorded up to the present date. This report presents three additional cases, in two of which metastasis had occurred at the time of surgery. The clinical presentation and the biological behaviour of these tumours are reviewed in detail, as also are recommendations regarding therapy. PMID- 6255921 TI - Malignant fibrous histiocytoma. AB - Seven cases of malignant fibrous histiocytoma are reported. Two patients had tumour involving the scrotum and small-gut mesentery, which are unusual primary sites, while three others with pulmonary metastases are alive five years since the appearance of these metastases. A review of the histogenesis, biological behaviour and the treatment of these uncommon tumours suggests that the prognosis is good even in the presence of advanced local or metastatic disease. Radiotherapy controlled the primary lesion in one patient and was effective in treating pulmonary metastases in three, suggesting that these tumours do show a response to radiotherapy. The prophylactic use of radiotherapy and chemotherapy awaits further evaluation. PMID- 6255922 TI - Modern methods for reliable preoperative localization of insulinoma. PMID- 6255924 TI - Incidence and distribution of "avian adenovirus group II splenomegaly of chickens". AB - Forty-six percent of 3,585 serum samples from 174 broiler-breeder chicken flocks in 9 states were positive for the precipitating antibody of hemorrhagic enteritis (HE) of turkeys/marble spleen disease (MSD) of pheasants. Seroconversion was detected only in flocks 19 weeks of age and older. The percent of individual serum samples positive within a flock increased with the age of the flock. PMID- 6255923 TI - Virus-mediated abrogation of chicken lymphocyte responsiveness to mitogenic stimulus. AB - We have found that various sorts of virus particles, including avian leukosis and sarcoma viruses, Sendai virus, Friend leukemia virus and murine mammary tumor virus, are able, upon coincubation with chicken peripheral lymphocytes and either Concanavalin A (Con A) or phytohemagglutinin (PHA), to inhibit the mitogenic responses that normally follow. Such inhibition is not dependent on the use of infectious virus, and can be documented by using particles whose infectivity has been abolished by irradiation with ultraviolet light. Lymphoid cells that had been preincubated with viruses at concentrations approximating 10 particles per cell and for only 2 hours were inhibited by as much as 83% in ability to respond to the lectins employed. These results appear to be mediated, at least in part, by a virus-induced factor with the capacity to abrogate the responsiveness of freshly obtained lymphocytes to mitogenic stimulus. This factor is devoid of interferon activity, as tested in a vesicular-stomatitis-virus plaque reduction assay. PMID- 6255925 TI - Onset of progeny immunity against viral arthritis/tenosynovitis after experimental vaccination of parent breeder chickens and cross-immunity against six reovirus isolates. AB - Immunization of breeder chickens by eyedrop with viral arthritis/tenosynovitis vaccine strain S1133 (73rd egg passage) gave no immunity against day-old oral challenge of their progeny at 1 week postvaccination of the breeders, but progeny immunity was observed at 3, 4, 5, 6, and 7 weeks postvaccination of the breeders. Oral cross-challenge of immune progeny with viral isolates from Connecticut, West Virginia, California, Indiana, Pennsylvania, and Minnesota showed that in vitro neutralization of an isolate by anti-S1133 antiserum correlated with in vivo immunity of the progeny against oral day-old challenge with such an isolate. PMID- 6255926 TI - Immune profile of infectious bursal disease: I. Effect of infectious bursal disease virus on peripheral blood T and B lymphocytes of chickens. AB - A comparison was made of absolute numbers of peripheral blood B and T lymphocytes, as defined by the anti-bursal and anti-thymus sera, in chickens infected with infectious bursal disease virus at one day and 3 weeks of age by age-matched controls. Birds were evaluated sequentially at weekly intervals for a period of 8 weeks postinfection. The severity of depressions of B-lymphocyte numbers was found to be age-dependent: the birds infected at one day of age showed a more severe depletion than those infected at 3 weeks of age. The T lymphocyte numbers were less markedly affected in infected chickens of either age group. PMID- 6255927 TI - Immune profile of infectious bursal disease (IBD). II. Effect of IBD virus on pokeweed-mitogen-stimulated peripheral blood lymphocytes of chickens. AB - Pokeweed-mitogen-stimulated peripheral blood lymphocytes from chickens infected with infectious bursal disease virus (IBDV) at 1 day and 3 weeks of age, together with those from uninfected age-matched control chickens, were examined at weekly intervals for their capacity to undergo in vitro terminal differentiation. This study included the determination of cytoplasmic-immunoglobulin (CIg)-containing peripheral blood lymphocytes and those bearing the surface membrane immunoglobulin (SmIg) cells to detect any defect in immunoglobulin synthesis and secretion, respectively. The results of our study indicated that there was a highly significant and pronounced progressive depletion of CIg-containing cells in chickens infected at 1 day of age. These findings suggest that IBDV affected the "immature" or precursor B cells to a far greater extent than mature B lymphocytes. PMID- 6255929 TI - Fowlpox virus in the Sudan. AB - A virulent fowlpox virus was isolated from a natural outbreak of the disease in the Sudan. The virus was used for experimental transmission of the disease to susceptible chickens. Scarification and intravenous methods were used to infect one-month-old chickens. Scarification induced typical pox lesions at 5-7 days postinoculation, whereas intravenous injection induced only swelling of combs or wattles, at 10-11 days postinoculation, although neutralizing antibodies against fowlpox virus were detected 2, 3, and 4 weeks postinoculation. The histopathological features of the pox lesions obtained in both natural and experimental infection were described. PMID- 6255928 TI - The response of broiler breeder chickens to parenteral administration of avirulent Pasteurella multocida. AB - Broiler breeder chickens were exposed to avirulent Pasteurella multocida at 14, 22, and 34 weeks of age either by stick wing 1 to 3 times or subcutaneously 3 times. Fowl pox vaccine was mixed with the first P. multocida exposure in some groups. Exposure did not impair egg production or hatch of fertile eggs. Challenge with pathogenic P. multocida serotype 1 at 68 weeks indicated that exposure to avirulent P. multocida 2 or 3 times provided better protection than 1 exposure. Mixing fowl pox vaccine with the avirulent P. multocida did not reduce immunity to fowl cholera or fowl pox. PMID- 6255930 TI - A new viral respiratory infection in parakeets. PMID- 6255931 TI - Preexposure to delta-9-THC blocks THC-induced conditioned taste aversion in rats. PMID- 6255932 TI - Effects of vanadate on the c-AMP system of the heart. PMID- 6255933 TI - Vanadate interaction with the Na, K-ATPase. An assay of serum vanadate based on the displacement of (48V) vanadate from Na, K-ATPase. AB - Under optimum conditions for vanadate binding to Na, K-ATPase equilibrium binding date for a range of vanadate concentrations were compiled. Scatchard plots indicated an identical binding capacity for vanadate and ouabain with conventionally prepared Na, K-ATPase batches. A method for determination of vanadate in serum based upon the high affinity of vanadate for Na, K-ATPase is described. The method takes advantage of the shift in equilibrium binding of (48V) vanadate upon addition of an aliquot of vanadate-containing serum. It is shown that the interplay between vanadate and ouabain in vanadate-facilitated ouabain binding to Na, K-ATPase leads to an enzyme-vanadate-ouabain complex to which vanadate is rather firmly bound. PMID- 6255934 TI - Significance of NADH-vanadate-oxidoreductase of cardiac and erythrocyte cell membranes. AB - Vanadate(V), which has positive inotropic, natriuretic and vasoconstrictive effects, is taken up by cardiac cells and erythrocytes in large quantities. Most of the intracellular vanadium is shown to exist as protein-bound vanadyl(IV), however Vanadate (VO3) is a powerful inhibitor of the (Na+ rK+)-ATPase and the Ca++-ATPase, whereas it stimulates adenylate cyclase of cardiac tissue. Vanadyl (VO2+) has no or much less effects on these enzymes. Plasma membranes of cardiac tissue (cat, calf, human) as well as erythrocytes contain an enzyme that converts vanadate(V) to vanadyl(IV) in the presence of NADH but not NADPH. The optimal conditions for this NADH-vanadate-oxidoreductase are: pH 6.8, 1 mM, NADH, 1.5 mM Va3VO4. Mg++ inhibits the enzyme half-maximally at 3 mM, Ca++ stimulates at low and inhibits at high concentrations (half-maximally at 0.8 mM). The enzyme is supposed to be located at the inner side of the cell membrane. Vanadate has been proposed as an ideal regulator of active cation transport across the cell membrane. The finding of a HADH-vanadate-oxidoreductase converting vanadate into the rather inactive vanadyl further supports this hypotheses. The amount of vanadate at active sites of the target enzymes might be responsible for the known vanadate effects. PMID- 6255935 TI - Regulation of active cation flux by vanadate in beating rat heart muscle cells in culture. AB - Looking for a supposed digitalis-like action of compounds of the trace element vanadium, we have investigated the influence of vanadate (Na3VO4) on beating and on active cation flux of [42K+] and [89Rb+] in cultured rat heart muscle cells: Na3VO4(10(-6)-10(-3)M) exerts a positive chronotropic effect and increases contraction velocity and beating automaticity of the cells. Vanadate-induced alteration of beating is paralleled by stimulated uptake of [42K+] and [86Rb+] up to 75%. This stimulation has to be attributed to increased activity of (Na++) ATPase and cannot solely be explained by the enhanced beating frequency. In contrast to ouabain, vanadate raises intracellular potassium content up to 15% and prevents cell contractures of ouabain-intoxicated heart muscle cells. The experimental data speak against a possible digitalis-like action of vanadate in cultured rat heart muscle cells. PMID- 6255936 TI - Effects of vanadate ions on action potentials and tension development in papillary muscles and cultured heart muscle cells. AB - In isolated and electrically driven (1/s) papillary muscles peak tension and, to a slighter degree, resting tension increased through treatment with Na3VO4 in concentrations higher than 10(-4)M. The positive inotropic effect was found to be transient. With vanadate, the resting membrane potential became more negative and rate of rise and overshoot of the action potential increased. Positivity and duration of the action potential plateau was markedly lessened by vanadate. These vanadate-induced changes of the electrical activity were not transient and hardly recovered during washout. Single cardiac cells in culture showed increased beat frequency when treated with vanadate ions in excess of 10(-4)M. This increase was fast but transient and led to cessation of spontaneous discharge. Simultaneously with the initial increase of beat frequency, maximum of rate of rise, diastolic potential and overshoot of the action potential also increased. Cells inactivated by vanadate (5 X 10(-4)M and higher concentrations) were relaxed in diastole and could be excited by intracellular stimulation. PMID- 6255938 TI - Nutrition, diet and cancer. PMID- 6255937 TI - Alpha-adrenergic vasoconstriction in arterial and arteriolar sections of the canine coronary circulation. AB - Using a method which allowed the in-situ measurement of segmental coronary vascular resistances, the reaction of arterial and arteriolar sections of the coronary vascular system to alpha-receptor stimulation was studied i anaesthetized dogs. The left coronary artery was cannulated, and the perfusion pressure was kept constant. Allowance was made for extravascular and metabolic influences of alpha-stimulation on coronary vascular resistances. On an average, submaximal alpha-stimulation with xylometazoline increased the arterial resistance by about 60% and the arteriolar resistance by about 90%. The cannulation of the left coronary artery increased the sympathetic reactivity of the arterioles. Moreover, xylometazoline increased the extravascular component of the coronary vascular resistance by about 4%. Thus it can be assumed that under normal in-vivo conditions alpha-receptor vasoconstriction might be less different in coronary arteries and arterioles. Since the arterial resistance ranges from 20% to 50% of total coronary resistance, a sympathetic vasoconstriction of this vascular section might lead even to a critical limitation of coronary blood flow. On the other hand, a predominant constriction in arterioles leads to an increase in peripheral coronary pressure, i.e. to a "reverse coronary steal phenomenon". PMID- 6255939 TI - Evidence that catecholamines stimulate renal gluconeogenesis through an alpha 1 type of adrenoceptor. AB - 1. Noradrenaline stimulates gluconeogenesis through an alpha-adrenoceptor in renal cortical tubule fragments from fed rats incubated with 5 mM-lactate. 2. The selective alpha 1-adrenoreceptor agonist methoxamine stimulated gluconeogenesis, but the selective alpha 2-adrenoceptor agonist clonidine was ineffective. 3. The selective alpha 1-adrenoceptor antagonist thymoxamine blocked the stimulatory effects on gluconeogenesis of noradrenaline and of oxymetazoline (a synthetic alpha-agonist). The selective alpha 2-adrenoceptor antagonist yohimbine was ineffective in this respect. 4. It is concluded that noradrenaline and oxymetazoline stimulate gluconeogenesis in rat kidney via an alpha 1-rather than an alpha 2-type of adrenoceptor. PMID- 6255940 TI - Glucagon-stimulated adenylate cyclase detects a selective perturbation of the inner half of the liver plasma-membrane bilayer achieved by the local anaesthetic prilocaine. AB - Prilocaine can increase the fluidity of rat liver plasma membranes, as indicated by a fatty acid spin-probe. This led to the activation of the membrane-bound fluoride-stimulated adenylate cyclase activity, but not the Lubrol-solubilized activity, suggesting that increased lipid fluidity can activate the enzyme. With increasing prilocaine concentrations above 10 mM, the membrane-bound fluoride stimulated activity was progressively inhibited, even though bilayer fluidity continued to increase and the activity of the solubilized enzyme remained unaffected. Glucagon-stimulated adenylate cyclase was progressively inhibited by increasing prilocaine concentrations. Prilocaine (10 mM) had no effect on the lipid phase separation occurring at 28 degrees C and attributed to those lipids in the external half of the bilayer, as indicated by Arrhenius plots of both glucagon-stimulated adenylate cyclase activity and the order parameter of a fatty acid spin-probe. However, 10 mM-prilocaine induced a lipid phase separation at around 11 degrees C that was attributed to the lipids of the internal (cytosol facing) half of the bilayer. It is suggested that prilocaine (10 mM) can selectively perturb the inner half of the bilayer of rat liver plasma membranes owing to its preferential interaction with the acidic phospholipids residing there. PMID- 6255941 TI - Subcellular distribution and some properties of N-ethylmaleimide-sensitive and insensitive forms of glycerol phosphate acyltransferase in rat adipocytes. AB - 1. Glycerol phosphate acyltransferase (GPAT) activities were measured in subcellular fractions obtained from rat epididymal adipocytes. These contained both N-ethylmaleimide-sensitive and N-ethylmaleimide-insensitive forms of the enzyme. 2. As shown by parallel measurements of marker enzymes, N-ethylmaleimide insensitive GPAT is most probably a mitochondrial activity, whereas N ethylmaleimide-sensitive GPAT is the microsomal enzyme. 3. Subcellular distributions are also reported for dihydroxyacetone phosphate acyltransferase (DHAPAT) (assayed with and without N-ethylmaleimide), monoacylglycerol phosphate acyltransferase (MGPAT) and Mg2+-dependent and Mg2+-independent forms of phosphatidate phosphohydrolase (PPH). PMID- 6255942 TI - Influence of starvation and clofibrate administration on oxidative phosphorylation by rat liver mitochondria. AB - Whole cells, homogenates and mitochondrial obtained from the livers of albino rats which were starved for 6 days or more showed a 50% decrease in oxidative activity. The decrease could be corrected by the addition of cytochrome c in vitro. The phosphorylative activity of mitochondria remained unaffected. The decrease in oxidative rate was not observed when starving animals were given the anti-hypercholesterolaemic drug clofibrate. The total cellular concentration of cytochrome c was not affected by starvation. However, the concentration of the pigment in hepatic mitochondria isolated from starving animals was less than half that in normal mitochondria. Clofibrate-treated animals did not show a decreased concentration of cytochrome c in hepatic mitochondria. Mitochondria isolated from starving animals, though deficient in cytochrome c, did not show any decrease in succinate dehydrogenase activity or in the rate of substrate-dependent reduction of potassium ferricyanide or attendant phosphorylation. In coupled mitochondria, ferricyanide may not accept electrons from the cytochrome c in the respiratory chain. Starvation decreases the concentration of high-affinity binding sites for cytochrome c on the mitochondrial membrane. The dissociation constant increases in magnitude. PMID- 6255944 TI - Phosphorylation of human fibrinogen in vitro with cyclic 3',5'-AMP-stimulated protein kinase and (32P)ATP. PMID- 6255945 TI - Endogenous 'ouabain like' activity in rat brain. PMID- 6255943 TI - The mechanism of proton translocation driven by the respiratory nitrate reductase complex of Escherichia coli. AB - Low concentrations (1-50mum) of ubiquinol(1) were rapidly oxidized by spheroplasts of Escherichia coli derepressed for synthesis of nitrate reductase using either nitrate or oxygen as electron acceptor. Oxidation of ubiquinol(1) drove an outward translocation of protons with a corrected -->H(+)/2e(-) stoichiometry [Scholes & Mitchell (1970) J. Bioenerg.1, 309-323] of 1.49 when nitrate was the acceptor and 2.28 when oxygen was the acceptor. Proton translocation driven by the oxidation of added ubiquinol(1) was also observed in spheroplasts from a double quinone-deficient mutant strain AN384 (ubiA(-)menA( )), whereas a haem-deficient mutant, strain A1004a, did not oxidize ubiquinol(1). Proton translocation was not observed if either the protonophore carbonyl cyanide m-chlorophenylhydrazone or the respiratory inhibitor 2-n-heptyl-4 hydroxyquinoline N-oxide was present. When spheroplasts oxidized Diquat radical (DQ(+)) to the oxidized species (DQ(++)) with nitrate as acceptor, nitrate was reduced to nitrite according to the reaction: [Formula: see text] and nitrite was further reduced in the reaction: [Formula: see text] Nitrite reductase activity (2) was inhibited by CO, leaving nitrate reductase activity (1) unaffected. Benzyl Viologen radical (BV(+)) is able to cross the cytoplasmic membrane and is oxidized directly by nitrate reductase to the divalent cation, BV(++). In the presence of CO, this reaction consumes two protons: [Formula: see text] The consumption of these protons could not be detected by a pH electrode in the extra cellular bulk phase of a suspension of spheroplasts unless the cytoplasmic membrane was made permeable to protons by the addition of nigericin or tetrachlorosalicylanilide. It is concluded that the protons of eqn. (3) are consumed at the cytoplasmic aspect of the cytoplasmic membrane. Diquat radical, reduced N-methylphenazonium methosulphate and its sulphonated analogue N methylphenazonium-3-sulphonate (PMSH) and ubiquinol(1) are all oxidized by nitrate reductase via a haem-dependent, endogenous quinone-independent, 2-n heptyl-4-hydroxyquinoline N-oxide-sensitive pathway. Approximate-->H(+)/2e(-) stoichiometries were zero with Diquat radical, an electron donor, 1.0 with reduced N-methylphenazonium methosulphate or its sulphonated analogue, both hydride donors, and 2.0 with ubiquinol(1) (QH(2)), a hydrogen donor. It is concluded that the protons appearing in the medium are derived from the reductant and the observed-->H(+)/2e(-) stoichiometries are accounted for by the following reactions occurring at the periplasmic aspect of the cytoplasmic membrane.: [Formula: see text] PMID- 6255946 TI - Restriction endonuclease analysis and nucleotide composition of satellite III DNA from Drosophila virilis. PMID- 6255947 TI - Studies on vitamin D3 metabolism. Discrete liver cytosolic binding proteins for vitamin D3 and 25-hydroxyvitamin D3. PMID- 6255948 TI - Partial beta-adrenergic receptor blockade in experimental bronchial asthma. PMID- 6255949 TI - Increase in liver and kidney deoxycytidine kinase activity linked to neoplastic transformation. PMID- 6255951 TI - Leukotriene A4: enzymatic conversion to leukotriene C4. PMID- 6255950 TI - Endothelial cell adenylate cyclase: activation by catecholamines and prostaglandin I2+. PMID- 6255952 TI - Effect of norepinephrine and dibutyryl cyclic AMP on S-100 protein level in C6 glioma cells. PMID- 6255954 TI - N-Bromosuccinimide fragments of protein A24 (uH2A): an implication that ubiquitin is the precursor of conjugation in vivo. PMID- 6255953 TI - The possible implication of membrane-associated actin in stimulus-secretion coupling in adrenal chromaffin cells. PMID- 6255955 TI - Specific receptor sites for alpha-tocopherol in purified isolated adrenocortical cell membrane. PMID- 6255957 TI - Isolation of native internal structural proteins of avian oncovirions by SP sephadex column chromatography. PMID- 6255956 TI - Rapid purification by affinity chromatography of rat brain pyridoxal kinase and pyridoxamine-5-phosphate oxidase. PMID- 6255958 TI - A fluorinated vitamin D3 analog with biopotency greater than 1 alpha, 25 dihydroxy vitamin D3. PMID- 6255959 TI - Induction of differentiation in a human promyelocytic leukemic cell line (HL-60). Production of granule proteins. PMID- 6255960 TI - Translocation of hepatocyte lysosomes following partial hepatectomy and its inhibition by colchicine. PMID- 6255961 TI - [Use of serum impregnanted paper disks for the identification of enterovirus in tissue culture]. PMID- 6255962 TI - [Serological survey of parainfluenza virus infection in cattle of Antioquia, Colombia, 1976]. PMID- 6255963 TI - [EV viruses and isolation of SLE, EE, group C and Group Guama arboviruses in the Amazon region of Peru in 1975]. PMID- 6255964 TI - [Herpesvirus and human cancer]. PMID- 6255966 TI - A comparison of the activity in vitro of different cephalosporins: cephalothin, cephradine, cephacetrile, cefaclor, cefuroxime and cefotaxime. AB - 6-cephalosporins (cephalothin, cephradine, cephacetrile, cefaclor, cefuroxime, cefotaxime) has been tested in vitro against 212 gram negative bacteria and 60 Staphylococci. Cefuroxime and especially Cefotaxime showed the highest activity against the gram negative bacteria, with a very low MIC. Cefotaxime also acted fairly well against several strains of Pseudomonas. Of the six cephalosporins tested, cephalothin gave the best results against the Staphylococci. PMID- 6255965 TI - [Detection of virus A antibody through epidemiology and diagnosis of hepatitis A]. AB - In the present work the Authors report the results of the research of HAAb in 383 subjects living in Rome with negative history for hepatitis (divided for age, sex and occupation) and in 64 acute non B hepatitis (HBsAg-). In the latter, the titer of HAAb was determined at the beginning and later during the course of the disease. A fractionation of 13 sera of these patients was done and the type of specific immunoglobulin was determined. Among the subject with negative history for hepatitis, 68.9% was positive during first 6 months of age 6.2% from 6 months to 5 y.o., 27.6% from 6 to 12 y.o., 45.4% from 12 to 17 y.o., 76.8% from 18 to 25 y.o., 82.2% from 26 to 45 y.o., 90.2% from 46 to 65 y.o.. There was no statistically significant difference either between males and females, or among various occupations. Among the 64 patients with non B hepatitis, 25 (39%) were hepatitis A (because they showed either a seroconversion for HAAb or a positive HAAb-IgM); 12 (18.7%) were non A-non B hepatitis because HAAb negative or HAAb positive but negative for HAAb-IgM; while 27 (42.2%) were impossible to classify because they showed a positivity for HAAb but not a seroconversion during the disease. The limit of the determination of HAAb and the utility of the research of IgM antibody for the diagnosis of hepatitis A are discussed. PMID- 6255967 TI - [Changes in cyclic AMP concentration of the rat preoptic region as a result of long term exposure to cold]. AB - The cAMP concentration in the preoptic region was studied in rats during exposure to low ambient temperature (Ta: -10 degrees C) and after return to control Ta (22 degrees C). With respect to control cAMP concentration, changes were observed consisting of a decrease (delta cAMP: 4.19 /+- 0.15 pM/mg Pr; p < 0.001) at low Ta and an increase (delta cAMP: 1.40 /+- 0.13 pM/mg Pr; P < 0.05) after return to control Ta. In contrast, cortical cAMP concentration decreased both at low Ta (delta cAMP: 2.94 /+- 0.09 pM/mg Pr; P < 0.005) and after return to control Ta (delta cAMP: 3.21 /+- 0.09 pM/mg Pr; P < 0.001). such cAMP changes in the preoptic region may be related to different activation levels of thermoregulatory and sleep mechanisms. PMID- 6255968 TI - "In vivo" and "in vitro" effects of a bacterial extract on Herpes Simplex Virus. AB - The present studies were designed to evaluate the effects of substance or substances extracted from Escherichia coli on Herpes Simplex Virus. The "in vivo" assays show that bacterial extract introduced i.p. in mice simultaneously with HSV2 brought about 100% of survival, but the inoculation of crude extract after virus challenge brought about complete mortality of mice. "In vitro" assays show that the crude extract reduced significantly the numbers of PFU; better results were obtained when the crude extract was inoculated before the virus inoculation. PMID- 6255969 TI - [Production of lipase from Staphylococcus aureus grown on glucose media. II) Synthesis and release of enzyme in media containing glucose and cyclic AMP]. AB - Catabolite repression by glucose on lipase from Staphylococcus aureus is revealed as inhibition of the appearance of the enzyme in the surrounding medium but not as synthesis; dibutyryl cAMP results in an induction of cellular membrane permeation of the synthesized enzyme towards the external medium. PMID- 6255970 TI - [DPA and clonazepam activity in febrile convulsions: preliminary results]. AB - A pharmacological trial has been performed for the prophylaxis of febrile convulsions in childhood. The administration of two antiepileptic drugs, Sodium Valproate and Clonazepam, reduces significantly seizures occurrence compared with unmedicated controls. Furthermore, Sodium Valproate has been found to be more effective than Clonazepam. Both anticonvulsants are thought to act by a Gabaergic modulation in CNS. PMID- 6255972 TI - [Production of corticosterone in vitro: role of PGE2]. AB - The Authors have studied corticosteron output and tissue levels of cAMP during superfusion with ACTH and/or PGE2 before and after preincubation with indometacin (2 microgram/ml) in beef adrenal glands isolated and superfused with Ringer solution. The Authors on the basis of Mieir studies, conclude that PGE2 can be considered as fixed intermediares of the corticosteroidogenetic action of ACTH. PMID- 6255971 TI - [Aldosterone production in vitro by angiotensin II: the role of Ca++]. AB - In beef isolated and superfused adrenal glands, the Authors have studied the production of aldosteron and tissue concentration of cAMP during superfusion with angiotensin II alone or preceededby preincubation with indomethacin or verapamil. In such experimental conditions the Authors could evidence that th aldosterone inductor effect of angiotensin II is not mediated by cAMP but by PGs and Ca++. PMID- 6255973 TI - Fluidity of erythrocyte membranes from patients with Duchenne muscular dystrophy: studies in intact erythrocytes and in ghosts. AB - We have studied the alterations of fluidity in intact erythrocytes and in erythrocyte membranes from patients with Duchenne muscular dystrophy. The interest of this study was to comparison directly two types of results; these demonstrate an increase of fluidity in the erythrocytic membranes, no changes are present when the label is incorporated in intact erythrocytes. It might be inferred that hypotonic haemolysis removes components that are more weakly bound in Duchenne membranes, and that exert an immobilizing effect on the membrane lipids. PMID- 6255974 TI - [Role of cGMP in the response of frog skin to noradrenaline]. AB - The effects of noradrenaline on cGMP levels of epithelial cells isolated from frog skin are reported. Noradrenaline does not change cGMP levels either in a medium containing Ca++ and Mg++, or without Ca++ or without Mg++. PMID- 6255975 TI - [Rapid induction of liver cirrhosis in rats by treatment with ethanol, carbon tetrachloride and progesterone]. AB - The administration of progesterone increases the degree of liver cirrhosis in rats treated with CCl4 and ethanol. Pseudolobulation with large amount of interstitial fibrosis are obtained after only 6 weeks of treatment. The ability of progesterone to suppress collagenase activity is supposed to be responsible of the strong increase of cirrhosis. PMID- 6255976 TI - [A common pool of adenylate cyclase for different types of afferent receptors]. AB - The authors investigate whether adenylate cyclase, that is a component of different receptors, i.e. the beta-adrenergic and H2-Histaminic ones of the heart, either plays a specific role for the activation of each receptor of forms the same pool for two types of receptors. On the mechanogram of guinea pig ventricle, stimulated by electric stimuli, an analysis of interferences among isoprenaline, propranolol, histamine and noradrenaline shows that isoprenaline inhibits histamine; in presence of propranolol the isoprenaline doesn't block histamine. Therefore the AA. conclude that adenylate cyclase is common to both receptors. PMID- 6255977 TI - Failure of neostigmine to prevent tubocurarine neuromuscular block in the isolated arm. AB - Neostigmine failed to modify the development of neuromuscular block in the presence of a high local concentration of tubocurarine. Only when the concentration of tubocurarine was reduced, and a suitable concentration gradient established between the receptor area and the plasma, did neostigmine increase the rate of recovery from the action of non-depolarizing neuromuscular blocking agents. PMID- 6255978 TI - Evaluation of a radioimmunoassay for IgM-class antibodies against cytomegalovirus. AB - A solid-phase radioimmunoassay (RIA-IgM) test for cytomegalovirus (CMV)-specific IgM-class antibodies is described and its potential diagnostic usefulness in adult patients is evaluated. IgM-class antibodies were readily detected by RIA in early convalescent sera from patients with serologically confirmed primary CMV infection, as well as in sera from patients with CMV mononucleosis. Serum specimens obtained several months after primary infection gave either negative results of low antibody titres, indicating that the IgM response is transient in these patients. CMV-specific IgM was also detected in 7 of 10 patients with symptoms and supportive serological evidence suggestive of recent active CMV infection. Conversely, 12 patients who were thought not to have experienced recent primary CMV infection, but whose sera gave high complement-fixing (CF) antibody titres, and 14 of 15 renal transplant recipients with reactivated CMV gave negative results in the RIA-IgM test. The results indicate that detectable IgM antibody production is a constant feature in patients with primary infection but not in patients who experience mild secondary attacks. The RIA-IgM test is highly virus-specific and can reliably be performed with unfractionated serum, provided that false reactivity due to rheumatoid factor (RF) is excluded. Thus RIA is a simple and specific technique which could be usefully applied as a diagnostic tool in a clinical situation and in research. PMID- 6255979 TI - Ultrastructural studies of erythropoiesis in beta-thalassaemia trait. AB - The erythropoietic cells of six cases of beta-thalassaemia trait were studied by electron microscopy and electron microscope autoradiography. Intracytoplasmic and intranuclear alpha-chain precipitates were found in some late polychromatic erythroblasts and intracytoplasmic precipitates were found in several marrow reticulocytes. This provides direct morphological evidence of unbalanced globin chain synthesis in the marrow. Several of the polychromatic erythroblasts and marrow reticulocytes contained autophagic vacuoles and showed a variety of other dyserythropoietic changes. Erythroblast profiles containing moderate quantities of precipitated alpha-chains usually suffered from a marked depression of protein synthesis. The proportions of marrow cells containing alpha-chain precipitates and displaying dyserythropoietic changes varied considerably from patient to patient. It is proposed that this variation largely reflects variations in the proteolytic capacity of the erythropoietic cells in different individuals and leads to different degrees of ineffective erythropoiesis in beta-thalassaemia trait. PMID- 6255980 TI - Levels of haemoglobin H and proportions of red cells with inclusion bodies in the two types of haemoglobin H disease. PMID- 6255981 TI - Role of family susceptibility, occupational and family histories and individuals' blood groups in the development of silicosis. AB - A previous investigation has shown that family susceptibility and occupational and family histories have a decisive role in the development of byssinosis among workers exposed to flax dust. Results of investigation of silicosis in 814 male workers exposed to silica-bearing dust showed that family susceptibility has an important role in the development of silicosis among examined workers, and workers whose fathers had an occupational history of exposure to silica-bearing dust were more resistant to the development of the disease than those with non exposed fathers. The degree of consanguinity of parents and individuals' blood groups, also, have a role. Workers with cousin parents were relatively highly susceptible to the development of silicosis as well as workers with blood groups "O" or "AB". It has been concluded that the investigated factors might have a role in the development of other occupational diseases and further investigations are indicated. PMID- 6255982 TI - ACTH and resistance of small blood vessels to trauma: use of mucosal petechiometry. AB - The effect of an intramuscular injection of ACTH on the resistance to trauma of oral mucous membrane blood vessels was assessed by petechiometry. In a double blind cross-over study involving 20 healthy volunteers, 18 showed a reduction in petechial count after the active injection but only nine did so after the injection of placebo. These findings may justify the use of ACTH in the management of patients with a history of haemorrhage after dental extraction. PMID- 6255983 TI - Association of alcohols with heme proteins: optical analysis and thermodynamic models. AB - At concentrations lower than those causing denaturation, methanol, ethanol, and 1 propanol produce changes in optical absorption of alkaline ferricytochrome c. These changes arise from weak equilibrium associations characterized by dissociation constants at 25 degrees C of about 4 and 2 M, respectively, for the methanol- and 1-propanol-ferricytochrome c complexes. The difference spectra and temperature dependence of enthalpy and entropy changes accompanying formation of methanol and 1-propanol complexes, as well as changes induced in the EPR spectra, are different and suggest distinct binding modes. Considered in conjunction with related parameters from ferrihemoglobin and ferrimyoglobin, the spectral and thermodynamic data are consistent with models in which methanol is bound directly to the ferric ion of cytochrome c, methanol and ethanol are bound directly to the ferric ions of hemoglobin and myoglobin, and 1-propanol is bound to a hydrophobic region of cytochrome c. Both the absolute and alcohol-induced optical difference spectra of these proteins have been simulated, the former through summation of Gaussian bands and the latter as the difference between two such summations, one with parameters slightly altered from the other. This analysis reveals and characterizes previously unresolved structure, which is discussed in terms of electronic transitions of the heme group and changes caused by differing interactions of the heme with surroundings. Similarity between the difference spectra produced by IHP perturbation of ferrihemoglobin and that from the difference between absolute spectra of ferrimyoglobin and ferrihemoglobin suggests that, with ferrihemoglobin as reference, the conformations about the hemes of ferrimyoglobin and of ferrihemoglobin-IHP are in some way similar. PMID- 6255984 TI - Proton and oxygen-17 magnetic resonance relaxation in Rhus laccase solutions: proton exchange with type 2 copper(II) ligands. PMID- 6255985 TI - Proton nuclear magnetic resonance studies of hemoglobins M Boston (alpha 58E7 His leads to Tyr) and M Milwaukee (beta 67E11 Val leads to Glu): spectral assignments of hyperfine-shifted proton resonances and of proximal histidine (E7) NH resonances to the alpha and beta chains of normal human adult hemoglobin. PMID- 6255986 TI - Constrained configuration of double-stranded ribonucleic acid in HeLa hnRNP and its relaxation by ribonuclease D. PMID- 6255987 TI - Deoxyribonucleic acid gyrase-deoxyribonucleic acid complex containing 140 base pairs of deoxyribonucleic acid and an alpha 2 beta 2 protein core. AB - Staphylococcal nuclease digestion of the complex between DNA and DNA gyrase yields a gyrase-DNA core particle composed of a 140 base pair DNA segment and an active gyrase enzyme. The partial specific volume and S20,w of this purified core complex are measured to be 0.70 cm3/g and 14.5 S, respectively, by sedimentation measurements in H2O and D2O media. The molecular weight of the core complex estimated from equilibrium centrifugation is 470 000; the ratio of the translational frictional coefficient to that of the unsolvated equivalent sphere is calculated to be 1.9. Treatment of free gyrase in solution with dimethyl suberimidate gives three cross-linked species of roughly equal amounts that can be identified as alpha 2, alpha 2 beta, and alpha 2 beta 2. When the gyrase core complex is treated with the same cross-linking agent, 70-80% of the protein is converted to the alpha 2 beta 2 species. These results establish that the gyrase DNA core complex contains a 140 base pair DNA segment and a tetrameric alpha 2 beta 2 protein. PMID- 6255989 TI - Determination of polypeptide amino acid sequences from the carboxyl terminus using angiotensin I converting enzyme. AB - A method for sequence analysis of polypeptides starting at the carboxyl terminus is described that utilizes degradation of the polypeptide into dipeptides with angiotensin I converting enzyme. Dipeptides were identified by gas chromatography mass spectroscopy. Dipeptide alignment was achieved by replicate digestion of the polypeptide after modification at the carboxyl terminus either by chemical or enzymatic removal of one residue or by addition of a single residue. The addition reaction involved coupling of L-alpha-aminobutyric acid under conditions described herein which yielded essentially complete conversions. Unlike sequence determination methods that commence from the polypeptide amino terminus, this procedure does not require that a polypeptide have a free amino terminus for successful application. A number of polypeptides with varying chain lengths (up to 49 residues), containing among them most of the common amino acids, have been successfully analyzed in amounts as low as 5 nmol. PMID- 6255988 TI - Reactions of nitric oxide with cytochrome c oxidase. AB - The reactions of nitric oxide (NO) with both oxidized and reduced cytochrome c oxidase are reported. NMR and mass spectroscopy were utilized to determine the products of the reactions; EPR and optical spectroscopy were employed to determine the states of the enzyme produced in each of these reactions. It was found that the enzyme catalyzes the consecutive oxidation and reduction of NO. A different cycle was observed when NO was added to the reduced enzyme, to the oxidized enzyme, or to the oxidized enzyme in the presence of azide. It was possible to observe the state of the enzyme at several points in each of these three cycles by varying the concentration of NO. The reactions of NO all involved a one- or two-electron redox step and could be accounted for by the involvement of only cytochrome a3 and Cua3. On the basis of these results, a mechanism for the reduction of dioxygen by the enzyme is proposed in which cytochrome a3 functions to anchor dioxygen and intermediates while remaining in the ferrous state, whereas Cua3 functions to accept electroins from cytochrome a/Cua and transfer them to dioxygen. PMID- 6255990 TI - Stereochemistry of the hydrolysis of adenosine 5'-thiophosphate catalyzed by venom 5'-nucleotidase. AB - The stereochemical problem involving a pro-pro-prochiral phosphorus center, the hydrolysis of adenosine 5'-monophosphate to adenosine and inorganic phosphate catalyzed by the venom 5'-nucleotidase, has been studied by use of chiral [16O, 17O, 18O]thiophosphates (Psi). (Rp)- and (Sp)-[alpha-18O1]Adenosine 5' thiophosphates (AMPS) were synthesized by a combined chemical and biochemical procedure. Hydrolysis of (Rp)- and (Sp)-[alpha-18O1]AMPS in H217O by 5' nucleotidase gave two enantiomers of chiral Psi of unknown configuration. A 31P NMR method based on the combination of the quadrupolar effect of 17O [Tsai, M.-D. (1979) Biochemistry 18, 1468-1472] and the 18O isotope shift [Cohn, M., & Hu. A. (1978) Proc. Natl. Acad. Sci. U.S.A. 75, 200-203] has been developed to analyze the configuration of chiral Pso. The results indicate that hydrolysis of (Rp)- and (Sp)-[alpha-18O1]AMPS in H217O gave (R)- and (S)- [16O, 17O, 18O]Psi, respectively. Therefore the hydrolysis of AMPS catalyze by the venom 5' nucleotidase must proceed with inversion of configuration at phosphorus, which suggests that the reaction is most likely an "in line" single displacement without involving a phosphoryl-enzyme intermediate and without pseudorotation. PMID- 6255991 TI - In vivo and in vitro inhibition of rat liver vitamin D3-25-hydroxylase activity by 19-hydroxy-10(S),19-dihydrovitamin D3. AB - Rats treated with varying amounts of 19-hydroxy-10(S),19-dihydrovitamin D3 prior to administration of physiologic doses of vitamin D3 exhibit normal intestinal calcium transport but are unable to mobilize bone calcium. In contrast, 19 hydroxy-10(R),19-dihydrovitamin D3 had no inhibitory activity. Circulating serum levels of 25-hydroxy[3H]vitamin D3 and 1 alpha, 25-dihydroxy[3H]vitamin D3 are markedly suppressed but not totally eliminated in animals predosed with 19 hydroxy-10(S),19-dihydrovitamin D3 before [3H]vitamin D3. Hepatic 25 hydroxy[3H]vitamin D3 levels were approximately equal in both 19-hydroxy-10(S),19 dihydroviotamin D3 treated and untreated rats. However, the rate of conversion of [3H]vitamin D3 to 25-hydroxyvitamin D3 in vivo is greatly reduced in the treated rats. The inhibitory vitamin analogue was also show to block hepatic microsomal 25-hydroxylation in vitro. These results indicate that 19-hydroxy-10(S),19 dihydrovitamin D3 is a specific inhibitor for a hepatic microsomal vitamin D3-25 hydroxylase system. PMID- 6255992 TI - Processing of the precursor to adrenocorticotrophic hormone and beta-lipotropin in monolayer cultures of mouse anterior pituitary. PMID- 6255993 TI - Mechanism of the stimulation of calcium ion dependent adenosine triphosphatase of cardiac sarcoplasmic reticulum by adenosine 3',5'-monophosphate dependent protein kinase. AB - Canine cardiac sarcoplasmic reticulum (SR) is known to be phosphorylated by adenosine 3',5'-monophosphate (cAMP) dependent protein kinase on a 22 000-dalton protein. Phosphorylation enhances the initial rate of Ca2+ uptake and Ca2+-ATPase activity. To determine the molecular mechanism by which phosphorylation regulates the calcium pump in SR, we examined the effect of cAMP-dependent protein kinase on the individual steps of the Ca2+-ATPase reaction sequence. Cardiac sarcoplasmic reticulum was preincubated with cAMP and cAMP-dependent protein kinse in the presence (phosphorylated SR) and absence (control) of adenosine 5' triphosphate (ATP). Control and phosphorylated SR were subsequently assayed for formation (4-200 ms) and decomposition (0-73 ms) of the acid-stable phosphorylated enzyme (E approximately P) of Ca2+-ATPase in media containing 100 microM [ATP] and various free [Ca2+]. cAMP-dependent phosphorylation of SR resulted in pronounced stimulation of initial rates and levels of E approximately P formed at low free [Ca2+] (less than or equal to 7 microM), but the effect was less at high free Ca2+ (greater than or equal to 10 microM). This stimulation was associated with a decrease in the dissociation constant for Ca2+ binding and a possible increase in Ca2+ sites. The observed rate constant for E approximately P formation of calcium-preincubated SR was not significantly altered by phosphorylation. Phosphorylation also increased the initial rate of E approximately P decomposition. These findings indicate that phosphorylation of cardiac SR by cAMP-dependent protein kinase regulates several steps in the Ca2+ ATPase reaction sequence which result in an overall stimulation of the calcium pump observed at steady state. PMID- 6255994 TI - Hydrodynamic properties of solubilized (Na+ + K+)-ATPase from rectal glands of Squalus acanthias. AB - (1) (Na+ + K+)-ATPas from the rectal glands of Squalus acanthias, solubilized in octaethylene glycol dodecyl monoether (2 mg detergent/mg protein), retains its activity for days when stored at 0 degrees C both with and without 20% glycerol. Glycerol protects partially against inactivation at higher temperatures. (2) Solubilization leads to a decrease in the amount of lipids bound per mg protein. 50 mol phospholipids and 40 mol cholesterol are bound per 265 000 g protein. 90% of the phospholipid is phosphatidylcholine (72%) and phosphatidylethanolamine (18%) and there is about 1 mol acidic phospholipid per 265 000 g. In addition, the protein has about 27 000 g carbohydrate as hexose, hexosamine and sialic acid bound per 265 000 g. (3) The calculation of the molecular weight from an In C vs. r2 plot obtained by sedimentation equilibrium centrifugaton in the presence of 560 microM detergent gives a molecular weight of the protein part of the active solubilized enzyme of 265 000 using the measured values for bound detergent, lipid (phospholipid + cholesterol) and carbohydrate. The sedimentation coefficient (S20,w) is 10.1 S, giving a Stokes' radius of 77 A. (4) An increase in detergent concentration to 56 mM dissociates the 10.1 S particle into particles with a sedimentation coefficient of 5.8 S and a molecular weight of 139 000 (Stokes' radius, 66 A). In the presence of this detergent concentration the enzyme is inactive. (5) The molecular weights of the soijm dodecyl sulphate solubilized, isolated alpha- and beta-chains are found to be 106 000 and 40 000, respectively. (6) It is concluded that the active solubilized enzyme is an (alpha beta)2 structure and that it dissociates into an enzymatically inactive alpha beta structure when the detergent-to-protein ratio is increased. PMID- 6255996 TI - A critical examination of the evidence for an MgATP-dependent proton pump in rat liver lysosomes. AB - (1) When lysosomes isolated from the livers of Triton WR 1339-treated rats were incubated for 30 min in the presence of 100 mM KCl and 14CH3NH2, a stimulation by MgATP of the calculated accumulation of the base was observed, in agreement with previous results (Schneider, D.L. (1979) Biochem. Biophys. Res. Commun. 87, 559 565). A similar stimulation was seen with MgITP. Excess EDTA had very little effect on the stimulation by MgATP. (2) There was little effect of MgATP or MgITP on the calculated accumulation of 14CH3NH2 if the base was added to the incubation medium 1, 3, 4 or 5 min before terminating the incubation instead of being present for the total incubation period of 30 min. (3) The accumulation of the basic dye, acridine orange, by a crude lysosomal preparation isolated from the livers of untreated rats was found to be stimulated by MgATP, in agreement with earlier results (Dell'Antone, P. (1979) Biochem. Biophys. Res. Commun. 86, 180-189). Similar results were obtained with a crude lysosomal preparation isolated from the livers of Triton WR 1339-treated rats. In both cases, the stimulation was partly oligomycin-sensitive. (4) There was very little or no effect of MgATP on the accumulation of acridine orange by preparations of pure lysosomes isolated from the livers of Triton WR 1339-treated rats. (5) Our data do not acquire us to postulate the existence of an MgATP-dependent proton pump in lysosomes. PMID- 6255995 TI - Coordinate interplay between (Na+ + K+)-ATPase and creatine phosphokinase optimizes (Na+/K+)-antiport across the membrane of vesicles formed from the plasma membrane of cardiac muscle cell. PMID- 6255997 TI - Plasma membrane heterogeneity in ascites tumor cells. Isolation of a light and a heavy membrane fraction of the glycogen-free Ehrlich-Lettre substrain. AB - In this work we report on the isolation of two plasma membrane fractions of a glycogen-free substrain of Ehrlich-Lettre ascites cells, a light fraction sedimenting in a sucrose gradient at 1.10 g/ml, and a heavy fraction sedimenting at nuclei by a combination of short-term swelling and mild Dounce homogenization. A 12 000 X g postnuclear pellet (PII) containing major portions of the plasma membrane marker enymes, 5'-nucleotidase, ouabain-sensitive (Na+ + K+)-ATPase and the alkaline phosphatase, was prepared by differential centrifugation. The two plasma membrane fractions were obtained by centrifugation on a discontinuous sucrose gradient, from which they were further purified on a linear sucrose gradient applying sedimentation velocity conditions only. Enrichment factors for the three marker enzymes were between 5- and 14-fold for the light fraction and between 3- and 7-fold for the heavy fraction with an overall yield of 1--4% and 0.5--1.7%, respectively, of cellular protein. Contamination of both fractions with nuclear material was minor. Mitochondrial contamination was about 8% for the light material and somewhat higher for the heavy material. In the light fraction, co-sedimentation of lysosomal and Golgi marker enzymes was detected. The presence of membrane structures of these organelles could not be confirmed definitely by electron microscopy. Differences in sialic acid content and phospholipid composition within the two fractions, especially in the relative proportion of lecithin to sphingomyelin, suggests differences in membrane fluidity. The light material showed mostly unit membrane vesicles in thin-section and freeze-etch electron microscopy, whereas the heavy fraction mainly consisted of sheet-like membrane fragments. PMID- 6255998 TI - The halide complexes of myeloperoxidase and the mechanism of the halogenation reactions. AB - The spectral changes caused by the addition of halides to myeloperoxidase (donor:hydrogen-peroxide oxidoreductase, EC 1.11.1.7) have been investigated and the dissociation constants of the enzyme-halide complexes have been determined. The pH dependence of the dissociation constants suggests that halide binding is associated with a protonation step in myeloperoxidase. Myeloperoxidase catalyzes the peroxidative chlorination and bromination of monochlorodimedone. It is shown that at low pH, chloride acts as a competitive inhibitor with respect to H2O2, whereas at higher pH, H2O2 inhibits the chlorination reaction. The dissociation constant (Kd) of the spectroscopically detectable complex and the Km for chloride are considerably smaller than the inhibition constant (Ki) for chloride. These halogenation reactions are strongly pH dependent, the logarithm of the Km for chloride varies linearly with pH. The position of the pH optimum of the chlorination and bromination reaction is a linear function of the logarithm of the [halide]/[H2O2] ratio. A mechanism of the chlorination and bromination reaction is suggested with substrate inhibition for both hydrogen peroxide and the halide. PMID- 6255999 TI - Properties of prolyl 4-hydroxylase containing firmly-bound iron. AB - 1. Prolyl 4-hydroxylase (prolyl-glycyl-peptide, 2-oxoglutarate:oxygen oxidoreductase, EC 1.14.11.2) was isolated in a form containing iron (0.85-1.1 mol Fe/mol enzyme). 2. The enzyme was pure according to gel electrophoresis and had a high specific activity (1.8-2.6 mumol . mi-1 . mg-1). 3. Experiments with metal chelators showed this iron to be firmly bound and to be required for catalytic activity. 4. According to EPR spectrometry the bound iron is not part of a [2Fe-2S] or a [4Fe-4S] cluster. 5. The enzyme activity is to a large extent independent of added Fe2+. 6. The enzyme activity is completely dependent on ascorbate. 7. In the absence of ascorbate but the presence of substrates the enzyme is irreversibly inactivated. 8. Continuous measurement of enzyme activity was possible by following oxygen uptake. PMID- 6256000 TI - Studies on the regulation of chloroplast fructose-1,6-bisphosphatase. Activation by fructose 1,6-bisphosphate. AB - Chloroplast fructose-1,6-bisphosphatase (D-fructose 1,6-bisphosphate 1 phosphohydrolase, EC 3.1.3.11) isolated from spinach leaves, was activated by preincubation with fructose 1,6-bisphosphate. The rate of activation was slower than the rate of catalysis, and dependent upon the temperature and the concentration of fructose 1,6-bisphosphate. The addition of other sugar diphosphates, sugar monophosphates or intermediates of the reductive pentose phosphate cycle neither replaced fructose 1,6-bisphosphate nor modified the activation process. Upon activation with the effector the enzyme was less sensitive to trypsin digestion and insensitive to mercurials. The activity of chloroplast fructose-1,6-bisphosphatase, preincubated with fructose 1,6 bisphosphate, returned to its basal activity after the concentration of the effector was lowered in the preincubation mixture. The results provide evidence that fructose-1,6-bisphosphatase resembles other regulatory enzymes involved in photosynthetic CO2 assimilation in its activation by chloroplast metabolites. PMID- 6256001 TI - RMI 12330A, an inhibitor of cyclic nucleotide phosphodiesterases and adenylate cyclase in kidney preparations. AB - N-(cis-2-phenylcyclopentyl)azacyclotridecan-2-imine hydrochloride (RMI 12330A) inhibited cyclic AMP and cyclic GMP phosphodiesterase activities in kidney preparations from rat and mouse. The drug was effective in the concentration range 0.1-1 mM. The agent was much less effective in inhibiting chick kidney cyclic nucleotide phosphodiesterases. The onset of inhibition of rat particulate cyclic AMP phosphodiesterase activities was rapid (less than 30 s) and irreversible. The inhibition of the low Km forms of cyclic AMP phosphodiesterase in mouse kidney homogenates was of the non-competitive type. RMI 12330A inhibited cyclic AMP phosphodiesterase activities in intact rat renal tubules. Adenylate cyclase activity, both basal and stimulated, was inhibited in all three species by the drug. Since RMI 12330A affects cyclic GMP metabolism as well as cyclic AMP metabolism, caution must be exercised in interpreting its effects upon cellular processes in terms of its actions upon the adenylate cyclase-cyclic AMP pathway alone. PMID- 6256002 TI - Adenylate cyclase in silkworm. Effects of adenosine 3'-phosphate and 2' deoxyadenosine 3'-phosphate on the enzyme system in fat body. AB - Adenosine 3'-phosphate and 2'-deoxyadenosine 3'-phosphate inhibit silkworm fat body adenylate cyclase. The inhibition has a rapid onset, and is dependent on the concentration of Mn2+ or Mg2+. The concentrations of 2'-deoxy-3'-AMP required for 50% inhibition (Ki) are 13 microM with 2 mM Mn2+ and 32 microM with 10 mM Mg2+. These Ki values are 7-30 times lower than that for 2'-deoxyadenosine. Stimulation of adenylate cyclase by NaF renders the activity more sensitive to the nucleotide inhibition, reducing the Ki value to 4 microM in the presence of Mn2+. The inhibitory activity is specific for adenine 3'-nucleotide; Ki for 2'-AMP and 5' AMP are ten times or more higher than that for 3'-AMP, and the other 3' nucleotides including 8-bromo-3'-AMP, 3'-IMP and 3'-GMP have little or no inhibitory activity. PMID- 6256003 TI - Purification and characterization of a plasminogen activator from mouse cells transformed by an oncogenic virus. AB - On the basis of cellular morphology, a subline of mouse sarcoma virus-infected 3T3 cells was selected which released a 48 000-dalton plasminogen activator at an approx. 40-fold higher rate than those of the parent line, and which continued to do so for several months when the cells were maintained in serum-free culture medium. Culture medium (3.5 l) containing 0.6 mg plasminogen activator per l was used to purify 620 micrograms of the enzyme 130-fold with a yield of 32% by affinity chromatography followed by anion exchange chromatography and gel filtration. Crucial for the yield was the use of a non-ionic detergent and of inhibitors of proteolysis to prevent adsorption and degradation, respectively. The purified enzyme was homogeneous as evaluated by SDS-polyacrylamide gel electrophoresis and had an isoelectric point of pH 9.2. The purified enzyme showed characteristics of a trypsin-like serine protease (labeling with [3H]diisopropylphosphorofluoridate which was prevented by p-nitrophenyl-p' guanidinobenzoate) and converted the single chain of human plasminogen into two chains of plasmin with electrophoretic mobilities identical to those of the chains formed by non-purified enzyme and by human urokinase. In the absence of inhibitors, solutions of purified enzyme were stable for 24 h at 4 degrees C at pH 3-9. PMID- 6256004 TI - Cyclic AMP in the cell cycle of Physarum polycephalum. AB - Cyclic AMP, [3H]thymidine incorporation, and DNA content were measured in the cell cycle of Physarum polycephalum. A sensitive radioimmunoassay was employed to assay cyclic AMP so that plasmodia could be assayed individually. In contrast to previously published results (Lovely, J.R. and Threlfall, R.J. (1976) Biochem. Biophys. Res. Commun. 71, 789-795), no pre-mitotic peak of cyclic AMP was detected. In seven experiments levels of cyclic AMP showed only small changes in individual experiments and ranged from 1-6 pmol/mg protein in different experiments. When plasmodia in the immediate premitotic period were collected on the basis of nuclear mitotic morphology, no evidence of a peak of cyclic AMP was found. Light was found to increase plasmodial cyclic AMP in a rapid, transient fashion. However, the brief exposure of cell cycle samples to light during collection did not induce any apparent cell cycle specific peaks of cyclic AMP. Although the occurrence of extremely rapid transient peaks of cyclic AMP in the cell cycle cannot be ruled out, it appears likely that the P. polycephalum cell cycle can proceed normally without major changes in cyclic AMP. PMID- 6256005 TI - Cytotoxicity of pyocin S2 to tumor and normal cells and its interaction with cell surfaces. AB - Cytotoxicity and adsorption of pyocin S2 produced by Pseudomonas aeruginosa M47 (PAO 3047) to virally transformed mammalian cells, human malignant cells and normal cells in the same species were studied. Pyocin S2 inhibited the growth of not only tumor cells (XC, TSV-5, mKS-A TU-7, HeLa-S3 and AS-II cells) but also normal cells (BALB/3T3 and BHK 21 cells). The inhibitory effects on the cells increased with an increase of pyocin S2 activity. On the other hand, there were some tumor cells (155-4 T2 and HCG-27 cells) and normal cells (normal rat kidney and human embryo lung cells) which were resistant to pyocin S2. The pyocin S2 activity was neutralized by the cell membrane preparations from pyocin S2 sensitive cells, but not by those from pyocin-resistant cells. This neutralization ability was inhibited by high concentrations of D-galactose, N acetyl-D-galactosamine and N-acetyl neuraminic acid and completely destroyed by periodate and neuraminidase. The inhibition by the saccharides was concentration dependent. These results suggest that the toxicity of pyocin S2 in the cell membrane and further, that the carbohydrate moiety, especially of D-galactose, N acetyl-D-galactosamine and sialic acid, may play an important role as an initial binding site for pyocin S2. PMID- 6256006 TI - Interaction between heparan sulphate chains. II. Structural characterization of iduronate- and glucuronate-containing sequences in aggregating chains. PMID- 6256007 TI - [Nuclear magnetic resonance study of water in Nitella mucronata cells]. AB - The properties of water contained in Nitella mucronata cells are examined by proton spin relaxation measurements. Two fractions of the cell water are observed. About 70% of cell water exhibits a longer relaxation time (T 1 congruent to 600 ms, T2 congruent to 300 ms), the exchange time of water molecules to and from hydration layer of macromolecules is equal to 0.06 ms and transforms into an ice-like state at --8 degrees C. About 30% of cell water exhibits a shorter relaxation time (T 1 congruent to 100 ms, T2 congruent to 50 ms), exchange of water molecules is not observed and there is no transformation into and ice-like state down to --30 degrees C. On the basis of the properties observed it could be concluded that the greater part of cell water behaves as "free water", while the lesser part of cell water may be regarded as a "bound water". PMID- 6256009 TI - [Volume increase during phase transition and the structure of water in native collagen]. PMID- 6256008 TI - [Relation between ouabain-insensitive differential sodium flux and sodium concentrations in solution]. AB - The dependence of net sodium ion flux on the external sodium concentration was studied under the inhibition of the sodium pump. A steady state balance of sodium ion fluxes occurred at external sodium concentration differing from the calculated one, therefore the existence of a non-diffusion component of sodium ion flux was evident. It was shown that the non-diffusion ouabain-insensitive sodium ion flux consisted of the sodium efflux not connected with chlorine efflux or potassium influx, and the sodium influx connected, perhaps, with potassium efflux. PMID- 6256011 TI - Properties of Na+, K+-ATPase of liver plasma membranes in the hamster. AB - This study was designed to establish the properties of liver plasma membranes (LPM) Na+,K+-ATPase in the hamster and to determine whether a similar assay may be used to measure enzyme activity in the hamster and in the rat. Maximal Na+,K+ ATPase activity was obtained when the assay medium contained 5 mM Mg APT2- with or without 1 mM free Mg2+, 120 mM Na+, 12,5 mM K+. The incubation must be performed at 37 degrees C, pH 7.4. In the absence of free Mg2+, the saturation curve with respect to the substrate Mg ATP2- resulted in biphasic complex kinetics with a maximal activity at a substrate concentration of 5 mM. In the presence of 1 mM free Mg2+ activation of Na+,K+-ATPase and modification of the kinetics were observed: the biphasic curve tended to disappear and to become of the Michaelis-Menten type. The apparent Km for Mg APT2- was 0.36 mM and the Vmax 34.5 mumol.h-1.mg protein-1. In the presence of 10 mM free Mg2+ a decrease in the Vmax was observed without any effect on the apparent Km for Mg APT2-. It is concluded that the same incubation medium may be used to assay LPM N+,K+-ATPase from hamster and rat and that the addition of 1 mM free Mg2+ to the incubation medium is recommended to obtain Michaelis-Menten kinetics in order to eliminate complex kinetics due to the absence of free Mg2+. PMID- 6256010 TI - [New approaches in eukaryotic DNA replication]. PMID- 6256012 TI - Effect of ejaculation frequency on the water volume of rabbit spermatozoa as determined by electron spin resonance spectroscopy. PMID- 6256013 TI - Estradiol-17 beta biosynthesis by the early bovine fetal ovary during the active and refractory phases. PMID- 6256014 TI - FSH receptor autoregulation and cyclic AMP production in the immature rat testis. PMID- 6256015 TI - Properties of simian adenovirus 7 after one single passage in simian marmoset lymphoblastoid cells transformed by Epstein Barr virus. AB - Simian adenovirus 7 gave an abortive infection in simian marmoset lymphoblastoid cells, B 95-8 and M 81 (transformed by Epstein Barr Virus) whereas non transformed simian lymphocytes could not replicate this virus. Electron dense incomplete particles with a lower density than standard virus in CsCl gradients were isolated. Virus yields were low and the percentage of cells containing viral antigen as measured by immunofluorescence was 0.01% for B 95-8 cells and still less for the M 81 cells. After a single passage in either lymphoblastic cell lines, they had a reduced oncogenicity in vivo. The polypeptide pattern analysis by PAGE showed some modifications. PMID- 6256016 TI - Adipocyte adenylate cyclase and alpha- and beta-adrenergic receptors in one case of multiple symmetric lipomatosis. AB - Adenylate cyclase activity and the number of alpha- and beta-adrenergic receptors (studied by radioligand binding techniques) were compared to adipocyte membranes prepared from lipomatous and normal adjacent adipose tissue of a patient with multiple symmetric lipomatosis. No difference could be detected between the normal and lipomatous adipose biopsies. These data strongly suggest that the impairement of catecholamine-induced lipolysis often reported in lipomas is related to a defect in the enzymatic steps localized beyond rather than before cyclic AMP synthesis. PMID- 6256017 TI - Purification and characterization of human alpha-galactosidase isozymes: comparison of tissue and plasma forms and evaluation of purification methods. PMID- 6256018 TI - Access of enzymes to brain following osmotic alteration of the blood-brain barrier. PMID- 6256019 TI - Enzyme therapy XVII: metabolic and immunologic evaluation of alpha- galactosidase A replacement in Fabry disease. AB - A pilot trial of enzyme replacement using splenic and plasma forms of alpha galactosidase A was undertaken in 2 brothers with Fabry disease, an X-linked glycosphingolipid storage disease. Partially purified preparations of alpha galactosidase A from human spleen and plasma Cohn fraction IV-1 were prepared aseptically for in vivo administration. The disappearance of enzymatic activity from plasma, levels of circulating substrate, and potential immune response were evaluated following IV administration of 6 unentrapped doses (2,000 U/kg) of each enzyme form to the respective recipient during a 117-day period. Repeated injections were well tolerated. The circulating half-life of the splenic form was about 10 min whereas that for the plasma form was approximately 70 min. No immune response was detected by skin and immunodiffusion tests or by alterations in the maximal activity or clearance kinetics for either enzyme following successive administrations. After each dose of the splenic form, the concentration of the accumulated circulating substrate globotriaosylceramide, decreased maximally (approximately 50% of initial values) in 15 min and returned to preinfusion levels by 2-3 hr. In marked contrast, injection of the plasma form decreased the circulating substrate levels 50-70% by 2-6 hr; the concentrations of globotriaosylceramide gradually returned to preinfusion values by 36-72 hr. Two consecutive doses of the plasma form, administered on days 1 and 3, reduced the circulating substrate concentration to normal levels. Prior to the 6th enzyme administration, circulating substrate was stable-isotope labeled by the infusion of dideutero-glucose, and the effects of each enzyme form on circulating substrate degradation and reaccumulation were determined. The results of this study indicated that labeled (newly synthesized) substrate reaccumulated following injection of the splenic enzyme whereas both unlabeled (previously stored?) and labeled substrate reaccumulated in the circulation after administration of the plasma form. These studies demonstrated the differential disappearance kinetics of the splenic and plasma forms of alpha-galactosidase A, their differential effects on circulating substrate degradation and reaccumulation, as well as the lack of an immune response to repeated administrations of these homologous, unentrapped enzymes. PMID- 6256020 TI - Techniques for the isolation of specific and functional templates. PMID- 6256021 TI - Receptors on hepatocytes that bind ligands containing fucosyl alpha 1,3 N acetylglucosamine linkages. PMID- 6256022 TI - [Transmembrane ion currents in pulmonary artery smooth muscle]. AB - Transmembrane ionic currents were investigated in the rabbit pulmonary artery smooth muscle under voltage clamp conditions with the use of the double sucrose gap method. With depolarizing pulses, there developed a fast inactivated outward current that was followed by a steady-state outward current. Tetraethylammonium (TEA) partly suppressed the outward current, and the fast inward current that preceded the fast outward one could be seen in these conditions. Appearance of the fast inward current in TEA-containing solution suggests the overlapping of the fast inward and outward currents. It appears that the resultant transmembrane current has an outward direction since in normal conditions the permeability of the fast potassium channels exceeds that of calcium channels. Conditioning hyperpolarization increased and depolarization decreased the fast outward current indicating that at the resting membrane potential a part of the potassium channels is inactivated and this inactivation is removed by hyperpolarization. PMID- 6256023 TI - [NADPH2 and organic hydroperoxide-dependent oxidation of adrenaline to adrenochromes in liver and brain microsomes]. AB - It was shown that oxidation of adrenaline to adrenochrome in microsomal membranes of the brain and liver in the presence of NADP . H2 or NAD . H2 is mainly accounted for by the formation of a superoxide anion radical. The formation of adrenochrome from adrenalin was found to depend on organic hydroperoxides (natural and synthetic). The organic hydroperoxide-dependent oxidation of adrenochrome involves singlet oxygen. In microsomal fractions of the liver the organic peroxide-dependent oxidation of adrenalin was catalyzed by cytochrome P 450. PMID- 6256024 TI - [Effect of indomethacin on cyclic nucleotide metabolism and vascular reactivity in rats]. AB - The content and metabolism of cyclic nucleotides in the aorta as well as contractility were studied in rats given different doses of indometacin. High doses of the drug (5 mg/kg) favored an abrupt decrease in cAMP and cGMP levels in the aorta and did not essentially affect vascular response to electric stimulation. Low doses of indometacin (2 mg/kg), particularly when coupled with salt load, resulted in the decreased cAMP/cGMP ratio and in the potentiation of vasoconstrictor responses. It has been demonstrated that the reduced proportion of cAMP in cyclic nucleotide metabolism is related to the activation effect of indometacin on cAMP-phosphodiesterase activity. The role of the prostaglandin cyclic nucleotide system in the vascular tone control is discussed. PMID- 6256025 TI - [Effect of apomorphine on rat brain opiate receptors]. AB - Stereospecific binding of apomorphine to rat brain opiate receptors was shown by assaying the competition of 7,8(n)--3H--naloxone and D-ala2-tyrosyl-3,5-3H- enkephalin (5-D-leucine) for opiate receptor binding. EC-NaCl50, the concentration of apomorphine which inhibited 50% binding of the radioactive naloxone and D-ala2, D-leu5-enkephalin in the absence of NaCl were 20 and 42 microM, respectively. EC+NaCl 50, the concentration of apomorphine which inhibited 50% binding of the radioactive naloxone in the presence of 100 mM NaCl was 17 microM. From the ratio of EC+NaCl 50 to EC-NaCl the value of "sodium shift" of effective concentration can be calculated as 0.85. From the data obtained it is concluded that apomorphine, like naloxone, is a "pure" antagonist but it has much less affinity for enkephalin and opiate binding sites. The probable mechanisms of the pharmacological action of apomorphine are discussed. PMID- 6256026 TI - [Membrane bodies in the nuclei of cerebral cortex neurons of the progeny of rats sensitized to brain antigen]. AB - The ultrastructure of sensomotor cortical neurons was studied by electron microscopy in young rats born to females sensitized with brain antigen before mating. Different membranous inclusions were discovered in neuronal nuclei. The membranous bodies were seen on the second day after birth and could be detected until day 60. It is suggested that the nuclear membranous bodies have been formed in the prenatal period. They may be the result of intraplacental impact of neuroantibodies on the developing embryonic brain. PMID- 6256027 TI - [Embryogenesis and early postnatal development of rats following transplacental sex hormone administration]. AB - A study was made of the effect of different doses of testosterone propionate, sinestrol, diethylstilbestrol and sigetin administered to rats during the last three days of pregnancy on the embryogenesis and postnatal development of the progeny. It was established that sex hormones (except sigetin) often disturb pregnancy, labor and lactation. They also exert a musculinizing and sterilizing effect on the progeny. Sigetin produces no action on embryogenesis or postnatal development of rats. PMID- 6256028 TI - Isolation and characterization of cloned DNA: the delta and beta globin genes in homozygous beta + thalassemia. AB - We have isolated and characterized a clone of human DNA from a patient with beta+ thalassemia containing the entire delta and beta structural genes and their flanking sequences. Partial Eco RI digestion of spleen DNA was used to obtain 15 to 20 kilobase (kb) pieces of human DNA that were then ligated to charon 4A lambda phage DNA. The 8 x 10(5) recombinants obtained were grown and screened for their content of beta gene sequences. Four positive clones were found, and one (beta T1-1) has been extensively analyzed. Subclones containing the entire beta gene and the large beta intervening sequence (IVS 2) have been isolated in the plasmid pBR 322. The fragments generated by restriction enzyme digestion in these subclones have been compared to those in similar subclones from normal beta genes. No differences have been found indication no significant rearrangements of deletions of the delta and beta genes. With the enzymes used, 11.2% of IVS 2 have been compared, and thus far no differences between the thalassemic and normal genes have been detected. The 24 enzymes used include Hph I, which recognizes the 5' end of IVS 2, and AIu I that cleaves at the 3' end. Thus, there appears to be conservation of nucleotide sequences at the ends of IVS 2 in this beta + thalassemia patient, although RNA metabolism studies suggest a possible defect in RNA processing. PMID- 6256030 TI - [Stimulation and inhibition of the sodium pump by cardiac glycosides]. PMID- 6256029 TI - Ectoenzymes on the surface of cells from human lymphoblastoid lines: 5' nucleotidase and phosphatase. AB - Activities of the ecto-enzymes 5'-nucleotidase (5'-N) and phosphatase were determined on the surface of intact cells from 15 different established lines of human B- and T-lymphoblasts. Whereas all the lines express phosphatase, 10 of the lines were negative for 5'-N. 5'-N-negative cell lines are found among B as well as T cells, and they do not carry cryptic enzyme activity. In a 5'-N-positive line activity of this enzyme is correlated with growth showing a peak during the logarithmic phase. On the other hand, inhibition of 5'-N does not change the growth curve of this line. Neuraminidase treatment of the cell surface brings about an increase in phosphatase but not in 5'-N activity. 5'-N of two B-cell lines of human peripheral blood lymphocytes shows complete crossreactivity with an antiserum obtained against human placental 5'-N. However, the enzyme of one lymphoma line with B-cell properties (EHR-A-Ramos) does not cross-react with this serum. The results are discussed with respect to suitability of these lymphoblast lines as model systems for the study of immunodeficiencies. PMID- 6256031 TI - Administration of marihuana smoke and synthetic cannabinoids to monkeys: methods, results and problems. PMID- 6256032 TI - Use of an extracorporeal glucose monitor for the diagnosis and surgical treatment of an insulinoma. AB - An extracorporeal glucose monitor (EGM) has been used in a patient with an insulinoma. This system, which continuously measures blood glucose, can be used in combination with a feedback-controlled glucose infusion to maintain glycaemia at any preselected level. It prevents the risk of severe hypoglycaemia during diagnostic tests (total fast, tolbutamide and insulin tolerance tests) as well as during surgery. It also helps in determining whether all the insulin-secreting tumour tissue has been removed. The EGM is thus helpful in the diagnosis and surgical treatment of insulinomas. PMID- 6256033 TI - Fulminant hepatic failure in childhood. PMID- 6256034 TI - Comparison of various treatments for irritable bowel syndrome. PMID- 6256035 TI - [Effect of aminopyridines on neuromuscular transmission]. PMID- 6256036 TI - Glutamate receptor binding to cat central nervous system membranes. AB - L-[3H]Glutamate exhibited specific binding to fresh membranes of cat CNS under physiological conditions of pH and temperature. This binding occurred in the absence of sodium ions. Kinetic analysis of the data for cerebellum suggested the presence of two distinct binding sites: a high-affinity process (Kd = 0.33 microM) with a capacity of 15 pmol/mg protein and a low-affinity process (Kd = 1.8 microM) which had a capacity of 65 pmol/mg protein. Several structural analogues of glutamic acid were able to appreciably inhibit the binding of [3H]glutamate. The distribution of glutamate binding between 12 regions of the CNS was measured. The amygdaloid complex exhibited the highest binding followed by hippocampus > hypothalamus identical to visual cortex identical to thalamus identical to caudate nucleus > olfactory bulb identical to tectum identical to cerebellum > dorsal pons identical to medulla > cervical spinal cord. These findings are consistent with the binding of [3H]glutamate being to its receptor. PMID- 6256037 TI - Reconstitution of lipoproteins. I. Lipid-protein interaction of high density apoproteins, purified apoA-I and apoA-II with dimyristoyl-lecithin and dimyristoyl-lecithin:cholesterol vesicles studied by isomeric spin-labelled lecithins. PMID- 6256038 TI - Reconstitution of lipoproteins. II. Lipid-protein interaction between dimyristoyl lecithin and dimyristoyl-lecithin:cholesterol vesicles and purified apolipoprotein C-I and C-III2 studied by isomeric spin-labelled lecithins. AB - The reconstitution of purified apolipoprotein C-I and C-III2 with sn-3 dimyristoyl-lecithin and sn-3-dimyristoyl-lecithin:cholesterol (10:1) vesicles was studied by electron spin resonance spectroscopy using isomeric 5'-, 12'-, and 16'-(N-oxyl-4",4"-dimethyloxazolidine)stearoyl spin-labelled lecithin probes. Results obtained from the temperature-induced changes of lipoprotein recombinants showed the hydrophilic nature of the lipid-protein interactions. The temperature induced phospholipid phase transition, as measured by 5'-(N-oxyl-4",4" dimethyloxazolidine)stearoyl spin-labelled lecithin probe in recombinants containing apoprotein C-1 or apoprotein C-iii2, is very broad and has a small cooperative unit indicative of extensive lipid-protein interactions occurring at the head group region of the phospholipid bilayer. When 12"- and 16'-(N-oxyl 4",4"-dimethyloxazolidine)stearoyl spin-labelled lecithins are used as probes in the same system, similar sharper and more cooperative lipid phase changes are detected. These results indicate a surface location for both apoprotein C-I and apoprotein C-III2 with respect to the phospholipid bilayer in lipoprotein recombinants with and without cholesterol. PMID- 6256039 TI - Evidence of prior infection with influenza A/Texas/77 (H3N2( virus in dogs with clinical parainfluenza. AB - Eighty dogs exhibiting clinical signs of respiratory disease were sampled for influenza virus isolation and serologically tested for hemagglutination inhibiting antibody to influenza A/Hong Kong/68, A/Victoria/75, A/Texas/77 and A/USSR/77. Forty-one animals without clinical signs of respiratory disease were also examined serologically. Hemagglutinating agents were isolated from nasal and/or pharyngeal swabs taken from 21 of the 80 dogs with clinical respiratory disease. Twenty of these 21 isolates were canine parainfluenza virus. Twenty-one of 80 clinically ill animals (26.3%) and eight of 41 normal animals (19.5%) had low level hemagglutination inhibiting antibody to influenza A/Texas/77. There was no evidence that human influenza caused the respiratory disease in the dogs included in this study, since none had an increase in hemagglutination inhibiting antibody to influenza in convalescent sera. The presence of antibody to A/Texas/77, however, does suggest the possibility that these dogs had at some time been infected with this virus, and that dogs could play a role in the epidemiology of influenza in man. PMID- 6256040 TI - Scanning electron microscopy of intestine of gnotobiotic piglets infected with porcine rotavirus. AB - The development of intestinal lesions caused by the porcine rotavirus were studied in six day old gnotobiotic piglets by scanning electron microscopy. The onset of diarrhea followed an incubation period of 17 to 31 hr. The first detectable lesion was observed in the ileum at 12 hr postinfection, a few hours before the onset of diarrhea. At this time enterocytes appeared swollen and began to separate from each other. Seventeen hours after the onset of diarrhea, lesions were quite severe jejunum and ileum. Enterocytes were detaching from the lamina propria leaving denuded areas. Microvilli were sparse on the cell surfaces and there was marked villous atrophy. Regeneration of ileal mucosa was evident at 4.8 days after the onset of diarrhea. Nine days after recovery from diarrhea the intestinal villi had returned to near its normal structure but there remained some evidence of mucosal damage. PMID- 6256041 TI - Naturally occurring picornavirus infection of domestic mink. AB - The isolation and preliminary characterization of a virus from domestic mink- are reported. The virus was tentatively classified as a member of the family Picornaviridae on the basis of its physicochemical properties. The mink virus was not neutralized by antiserum to some known members of the calicivirus genus, which included the nine serotypes of vesicular exanthema of swine virus, ten serotypes of San Miguel sea lion virus and feline calicivirus. Seroepidemiological studies indicated that the incidence of mink virus infection was widespread in domestic mink populations. Although the virus was isolated from mink on ranches with a history of hemorrhagic pneumonia (pseudomonas pneumonia), no specific disease process could be attributed to the virus infection. PMID- 6256043 TI - Motor radiculopathy--an unusual presentation of multiple sclerosis. AB - A 28 year old female presented with clinical and electrical evidence indicative of L5 motor radiculopathy. Subsequently she was found to have symptoms and signs of multiple sclerosis. When clinical assessment and investigation fail to disclose a cause then demyelinating disease should be considered in the differential diagnosis of motor radiculopathy. PMID- 6256044 TI - 1980 Gallie Memorial Lecture. Lung cancer in historical perspective: lessons from the past, implications of present experience, challenges for the future. PMID- 6256042 TI - The role of trypsin in plaque formation by simian rotavirus SA-11. AB - The role of trypsin in plaque production by simian rotavirus SA-11 monolayers of MA-104 cells are investigated. Initial trypsin treatment of the virus alone or its presence only during the early phases of virus-cell interaction was found to be insufficient for plaque production by the virus. Presence of trypsin (5 microgram/mL) in the agar overlay throughout the five day incubation period was essential for the optimal development of the virus plaques. Production of plaques by the incorporation of trypsin in the overlay was not due to the enzymatic degradation of any plaque-inhibitors in the agar used. Experiments using high (4 PFU/cell) and low (35 PFU/10(6) cells) multiplicities of infection suggest that trypsin added to fluid maintenance medium facilitates the cell-to-cell spread of progeny virus particles. Therefore, the enzyme incorporated in the agar overlay appears to play a similar role thereby assisting in the formation of SA-11 plaques. PMID- 6256046 TI - High-fibre diets for diabetic and hypertriglyceridemic patients. AB - Diets high in complex carbohydrate result in lower insulin requirements than the high-fat diets conventionally used to treat diabetes. Accompanying unacceptable increases in fasting triglyceride levels can be overcome by increasing the fibre content of the diet. In diabetics a diet providing 70% of energy from carbohydrate and containing 35 to 40 g of fibre per 1000 Cal will rapidly reduce the plasma glucose level and the requirement for insulin or sulfonylurea. It will also lower the serum cholesterol and triglyceride levels in individuals with hypertriglyceridemia. These improvements are maintained in patients following a modified high-carbohydrate, high-fibre diet providing 55% to 60% of energy by carbohydrate (75% of which is complex), 15% to 20% by protein and 20% to 30% by fat, with 25 g of plant fibre per 1000 Cal. With long-term use (for up to 48 months) of the maintenance diets patients maintained or corrected their body weight, and no nutritional deficiencies were observed. PMID- 6256045 TI - Labetalol: potent antihypertensive agent that blocks both alpha- and beta adrenergic receptors. AB - Labetalol was administered as the sole antihypertensive agent to 20 ambulatory patients with mild to moderate hypertension. The mean systolic and diastolic blood pressures (+/- standard error of the mean) with the patients sitting fell significantly (P < 0.001), from 145.5 +/- 3.2 and 103.7 +/- 1.6 mm Hg respectively at the start of labetalol therapy (after a period free of antihypertensive medication) to 125.7 +/- 2.0 and 87.2 +/- 1.1 mm Hg by the end of the trial. The diastolic blood pressure was well controlled (90 mm Hg or less) with labetalol therapy in 90% of the patients. The medication was well tolerated, and no orthostatic fall in the diastolic blood pressure was observed. Pharmacologically labetalol most closely resembles a combination of a nonselective beta-adrenergic blocker like propranolol and a postsynaptic alpha adrenergic blocker like prazosin. PMID- 6256047 TI - Serological survey for human arbovirus infections in the province of Quebec. PMID- 6256048 TI - Chemotherapy versus chemoimmunotherapy for small-cell undifferentiated carcinoma of the lung. AB - Thirty-eight patients with small-cell carcinoma were treated with cyclophosphamide, Adriamycin, and VP16-213 + or - MER. Response and survival of the six patients who received radiotherapy prior to entering the study were inferior compared with patients who received chemotherapy alone. Of 32 previously untreated patients, 13 had limited and 19 had extensive disease. Ninety-seven percent of these 32 responded and 63% achieved complete remission (CR). All patients with limited disease had a response and 77% achieved CR. Patients with extensive and limited disease had 91/2 months (range 1-26 months) and 14 months (range 31/2 -42 + months) median survival, respectively. The median survival for all complete responders irrespective of extent of disease was 16 months (range 6 42 + months). Three patients with limited disease are disease free more than 34 + months and off all therapy 10 + to 18 + months. Eighteen of 38 patients required antibiotics for fever during neutropenia. Eight patients had MER fevers and nine had serious infections. There were four drug-related deaths. MER therapy did not influence response rate, drug toxicity, or survival, but did add morbidity. This combination chemotherapy alone is an effective treatment for previously untreated small-cell lung cancer patients regardless of extent of disease. PMID- 6256050 TI - Evaluation and radiotherapy implications of chest relapse patterns in small cell lung carcinoma treated with radiotherapy-chemotherapy: study of 34 cases and review of the literature. AB - Evaluation and radiotherapy implications of chest relapse patterns in small cell lung carcinoma treated with chemotherapy and radiotherapy to the chest and brain. Emphasis was placed on analysis of patterns of chest disease relapse, chest complications, and sites of initial chest disease relapse in relation to volume treated by radiation. These results were compared with published reports. Of 17 cases with disease limited to the chest (LD), nine (53%) died of chest related complications, seven of these (41%) with chest disease recurrence. However, in five of these seven cases (72%), recurrences appeared initially outside the irradiated volume, in spite of 1-2 cm of safety margin, mostly in the ipsilateral lung, while the primary was without evidence of growth. Hence, chest disease relapse does not necessarily mean radiotherapy failure, as only 2 of the 17 cases (12%) had definite tumor growth in the irradiated field. This point is not properly emphasized in the literature, where marked discrepancies among authors reporting chest disease relapses are present. We elaborate about factors that will affect results, like frequency of follow-up x-rays, tumor size, site of chest disease relapse, and criteria to define tumor relapse. More autopsy and chest diagnostic studies are needed to investigate patterns of tumor spread within the lung. Survival alone is too broad a factor to measure the impact of radiotherapy in treatment. We need more understanding of the mechanisms of chest disease relapse to obtain a better design of radiotherapy ports. Systemic disease was the main cause of death in 17 patients with extensive small cell lung carcinoma, and routine chest irradiation cannot be justified although it might be of help for chemotherapy responders who are expected to have long survival. PMID- 6256049 TI - Small-cell carcinoma of the lung: a five-year experience with combined modality therapy. AB - In the past five years, we have treated 89 patients with small-cell carcinoma of the lung with radiotherapy plus one of three chemotherapy programs. The 24 patients with disease confined to the chest (Stage IIIMO) had an 87% response rate to the combined modalities (79% complete responses) and a median survival of 18 months; 13 patients with disease confined to the chest and ipsilateral supraclavicular nodes (Stage IIIMOSCN +) had an 84% response rate (69% complete responses) and 11-month median survival; the 52 patients with distant metastases (Stage IIIMI) had a 71% response rate (15% complete responses) and eight-month median survival. Survival was not affected by adding prophylactic cranial irradiation to the latest regimen, although the CNS relapse rate was reduced. We conclude that our three chemotherapy programs to date differ very little in their effect on survival of patients with metastatic disease. New and more vigorous approaches, possibly including surgery, need to be tested for the management of disease confined to the chest. The designation of patients as Stage IIIMOSCN + is valid because such patients have better survival rates than patients with distant metastatic disease. PMID- 6256051 TI - ACTH-secreting medullary carcinoma of the thyroid: monitoring of clinical course with calcitonin and cortisol assays and immunohistochemical studies. AB - The clinical course of a patient with Cushing's syndrome secondary to metastatic medullary carcinoma of the thyroid was documented with serial calcitonin and cortisol assays and tumor immunohistochemistry studies. Cortisol levels were originally markedly elevated but returned to normal after total thyroidectomy. These levels rose again when the patient developed liver metastases but normalized during chemotherapy, never to rise again despite the appearance of cervical lymph node metastasis. Calcitonin levels remained elevated throughout the course. The original tumor was composed of two cell lines: one containing both calcitonin and ACTH and another containing only calcitonin-reacting cells. However, the cervical metastasis showed a marked decrease in both cell lines with fever than 1% of cells reacting to ACTH, and only 25% to calcitonin. The almost total disappearance of ACTH-reacting cells may have been therapeutically induced or may represent a consequence of tumor progression. PMID- 6256052 TI - Hydrophilic macromolecules of steroid derivatives for the detection of cancer cell receptors. AB - Based on a study of 118 breast cancers, the majority of human mammary carcinomas were found to be composed of largely estrogen receptor-negative cancer cells. Only in about 20% of the tumors do the estrogen receptor-positive cancer cells exceed or equal the receptor-negative ones in number in an invariably heterogeneous cancer cell population. The number of progesterone receptor positive cancer cells appears to be even less than that of the estrogen receptor positive ones in any given tumor. Very often all three sex-steroid receptors can be demonstrated in the same cancer cells. These results indicate that this histochemical approach may provide an efficient, inexpensive, and potentially more accurate method for the assessment of all sex-steroid receptors in human breast cancer. PMID- 6256053 TI - Comparison of biochemical and histochemical techniques for estrogen receptor analyses in mammary carcinoma. AB - Three histochemical techniques for estrogen binding localization in tissue sections were compared to sucrose density gradient analyses for estrogen receptor in 186 breast carcinomas. Apparent localization to epithelial elements was noted using 6-BSA-Fluor-CMO-17 beta-estradiol, 17-BSA-Fluor-TSC-estrogen, and polyestradiol phosphate/anti-estradiol antibody methods. The correlation between the histochemical methods and standard sucrose density gradient techniques was poor for the polyestradiol antibody method and the 6-BSA-fluor-CMO-17 beta estradiol techniques. While an improved correlation was observed with the 17-BSA Fluor-TSC-estrogen compound, the compound's binding was not effectively blocked by preincubation with diethylstilbestrol. This failure to show convincing saturability of binding, combined with problems of extraction of soluble receptor proteins in the aqueous incubation media and washed from cells rendered permeable by cryostat sectioning, indicates that several areas will require clarification before histochemical techniques can begin to be considered as a method for estrogen ""receptor" analyses in the clinical evaluation of breast neoplasms. PMID- 6256055 TI - Correlation of hormone receptors with pathological features in human breast cancer. AB - Correlations have been found between certain pathologic features and estrogen and progesterone receptors status of mammary carcinoma. Well-differentiated carcinomas were more frequently receptor positive than poorly differentiated tumors. An increasing degree of lymphocytic and plasmacytic infiltrate in the tumor was associated with a decreasing incidence of estrogen receptor activity. In addition, elastosis in primary carcinomas has been correlated with response to endocrine therapy in patients with advanced disease. With increasing amounts of elastosis in the primary tumor, there was an increase in the response rate. Also, patients with estrogen receptor positive tumors with no elastosis showed a response rate similar to that of estrogen receptor-negative tumors. Hormone receptor analysis is most valuable when considered with other factors. PMID- 6256054 TI - Correlation of estrogen and progesterone receptors with histologic differentiation in mammary carcinoma. AB - Using a modification of the histologic grading system of the NSABP, we observed a trend towards higher levels of estrogen (E2R) and progesterone receptor (PR) content in well (grade I) and moderately (grade II) differentiated mammary carcinomas. This relationship between receptor content and histologic grade is enhanced by considering estrogen and progesterone receptor simultaneously. The rank correlation between the quantitative levels of E2R and PR was 0.74 among histologic grade I tumors and 0.64 among histologic grade II tumors. Among the grade III carcinomas, the majority of tumors displayed either a paucity of measurable receptor or a divergence between levels of estrogen versus progesterone receptor (r = 0.19). The use of ultrastructural evaluation of features of differentiation is discussed in the evaluation of grade III tumors and in the evaluation of specific histologic types of mammary carcinoma. PMID- 6256056 TI - Histochemical assay of estrogen and progesterone receptors in breast cancer: correlation with biochemical assays and patients' response to endocrine therapies. AB - Estrogen (ER) and progesterone (PgR) receptors were assayed by histochemistry in primary, recurrent, and metastatic breast cancer. Ligand-conjugates composed of 17 beta-estradiol and 11 alpha-hydroxyprogesterone covalently linked to bovine serum albumin and labelled with fluorescein isothiocyanate were employed. Results were compared with those of conventional biochemical receptor assays and correlated for ER in 92% of 314 tumors and for PgR in 86% of 86 specimens. ER and PgR determinations by both assay systems were correlated with clinical response to various endocrine therapies in 40 women with Stage IV disease. The histochemical assay enabled successful prediction of response in 80% of cases including eight which could not be fully analyzed biochemically. PMID- 6256057 TI - Steroid receptor interactions in human breast carcinoma. AB - Sucrose gradient centrifugation of estrogen and progestin receptors in cytosol preparations revealed that the majority of human breast tumors contained two molecular forms sedimenting at either 8S or 4S. Few tumors exhibited profiles containing predominately the 8S form or the 4S form alone. Molecular heterogeneity of the estrogen receptors in cytosol was demonstrated with regard to surface charge using ion-exchange chromatography and isoelectric focusing. The molecular properties of estrogen receptors in breast tumor biopsy specimens appear to be related to clinical responsiveness of patients given hormonal manipulations. These data and other findings related to the clinical utility of steroid receptor quantification impose a requirement for rigid quality control of analyses by the laboratory. The composition, evaluation, and distribution of tissue reference powders for establishing uniformity and quality control of steroid receptor analyses used in cooperative clinical trials of breast cancer treatment are described. This approach ensures meaningful correlations between laboratory results and clinical response. PMID- 6256058 TI - Transformation-dependent effect of dibutyryl cyclic AMP on surface properties of rat cultured cells. AB - The possible differential effect of dibutyryl cyclic AMP on the surface properties of ts-NT3-KR rat cells that express a normal phenotype at 37 degrees C and a transformed morphology and behavior at 33 degrees C has been studied. Electrophoretic examination of glycosylated macromolecules revealed a 350,000 dalton glycoconjugate in phenotypically normal cells but not in the corresponding samples from phenotypically transformed cells or in phenotypically "normal" cells rounded by exposure to the cyclic nucleotide. A decreased exposure of a major 100,000 dalton surface component characteristic of cells that expressed a transformed phenotype, was observed when the corresponding cultures were exposed to dibutyryl cyclic AMP. No change in the 230,000 dalton fibronectinlike molecule of phenotypically normal cells was apparent even in the corresponding cultures exposed to the cyclic nucleotide. PMID- 6256059 TI - Antigenic modulation and down regulation-their similarities suggest they may have a common origin. AB - Antigenic modulation, the antibody-induced disappearance of membrane-associated determinants of neoplastic cells, has a fundamental similarity to the down regulation of receptors for hormones and other ligands affecting the physiology of various nonneoplastic cell types. After hormone stimulation, cells previously responsive become refractory to further stimulation. Diminution in responsiveness correlates with a quantitative reduction in the numbers of specific complementary hormone receptors present. Murine leukemia cells, as one example "escape" antibody-mediated destruction through the mechanism of antigenic modulation. Resistance of the cells correlates with a reduction of the numbers of specific antigens present. In both down regulation and modulation, continued cellular metabolism in the absence of ligand leads to a re-expression of the hormone receptor/membrane antigen involved. It is postulated that the two phenomena have evolved from similar underlying cellular mechanisms. PMID- 6256060 TI - Thermosensitivity of the membrane potential of normal and simian virus 40 transformed hamster lymphocytes. AB - The effects of temperature in the fever range (37-42 degrees) on the membrane potentials of normal and simian virus 40-transformed hamster lymphocytes were analyzed. The transmembrane distributions of radiolabeled triphenylmethylphosphonium and thiocyanate were measured, and they provide upper and lower limits for the normal cell membrane potential at 37 degrees of -48 +/- 6 (S.D.) and -31 +/- 5 mV and for the tumor cells, -36 +/- 4 and -19 +/- 2 mV. The mitochondrial contribution to the triphenylmethylphosphonium-measured membrane potential, 5 to 10 mV for both splenocytes and simian virus 40 transformed lymphocytes, was estimated by utilizing antimycin A and carbonylcyanide-m-chlorophenylhydrazone to inhibit generation of a mitochondrial membrane potential. Incubation for 1 to 2 hr at 38-42 degrees resulted in a 6- to 15-mV depolarization of normal cells and a 2- to 6-mV hyperpolarization of tumor cells. Both depolarization and hyperpolarization were fully reversible by subsequent incubation at 37 degrees and insensitive to antimycin A and carbonyl cyanide-m-chlorophenylhydrazone. The membrane potential of normal splenocytes when measured with triphenylmethylphosphonium at 37 degrees was depolarized by 35% with 1 mM ouabain and thermally induced depolarization was blocked. The membrane potential of tumor cells at 37 degrees was insensitive to ouabain; however, the hyperpolarization at 40 degrees was inhibited. The membrane potential of normal lymphocytes stimulated with phytohemagglutinin was depolarized relative to that of nonstimulated control cells and assumed the thermal response characteristics of tumor cells. PMID- 6256061 TI - Inhibiton of phorbol ester-stimulated chemiluminescence in human polymorphonuclear leukocytes by retinoic acid and 5,6-epoxyretinoic acid. AB - Chemiluminescence (CL) is an index of both the generation of and reactions mediated by O2-. and 1O2. The tumor promoter, 12-O-tetradecanoylphorbol-13 acetate (TPA), is a potent stimulator of CL by human polymorphonuclear leukocytes; treatment with TPA (100 ng/ml) provokes a CL response that peaks within five min and persists for over 30 min. The response is proportional to concentration over the range of one to 100 ng/ml. The ability of different phorbol diesters to stimulate both CL and O2-. production correlates with their relative activities as tumor promoters in vivo. Non-phorbol diester tumor promoters such as iodoacetic acid, anthralin, and tween 60 are inactive in this system. The TPA-mediated stimulation of CL can be inhibited by retinoids; cells preincubated for 15 min with 100 microM retinoic acid show only a marginal CL response to TPA. Addition of retinoic acid to resting polymorphonuclear leukocytes results in a transient burst of CL without concomitant O2-. release, observations indicative of an excitable substrate. A similar CL response is seen when retinoic acid is incubated with potassium superoxide in a cell-free system. 5,6-Epoxyretinoic acid, and even more effective inhibitor of TPA-stimulated CL than retinoic acid when added simultaneously with TPA, does not undergo these two CL reactions. Thus, it appears that retinoic acid may undergo oxidative activation to a species that exert enhanced antipromoter activities. Polymorphonuclear leukocytes provide a useful system for exploring the roles of reactive oxygen species in the mechanism of action of both TPA and retinoic acid. PMID- 6256062 TI - Interaction of the alkylating antitumor agent 2,3,5 tris(ethyleneimino)benzoquinone with the plasma membrane of Ehrlich ascites tumor cells. AB - The effect of the alkylating agent 2,3,5-tris(ethyleneimino)benzoquinone (Trenimon) on the uptake of 2-aminoisobutyric acid, 1-aminocyclopentane-1 carboxylic acid (cycloleucine), 3-O-methyl-D-glucose, and 86Rb was studied. All transport studies were performed at nonsaturating conditions where the specific transport system was rate limiting for the uptake. The activities of all systems are reduced after treatment with the alkylating agent. The impairment of the plasma membrane is expressed 30 sec after exposure to the drug, as measured by the 86Rb uptake, and lasts for at least 12 hr according to the reduced 3-O-methyl D-glucose uptake. Inhibition of protein synthesis by cycloheximide for 2 hr does not affect the uptake of 86Rb. The short interval which is necessary before an inhibition of 86Rb uptake can be registered and the resistance of the 86Rb transport system to an inhibition of protein synthesis are considered as indicative for a direct alkylation of a membrane constituent. Treatment with the alkylating agent increases the cyclic adenosine 3':5'-monophosphate of the cells. This effect is not due to an effect on adenylate cyclase or the membrane-bound cyclic adenosine 3':5'-monophosphate phosphodiesterase. In view of the known correlations between plasma membrane functions and the regulation of cell division, it is proposed that the growth inhibition by Trenimon of Ehrlich ascites tumor cells may be caused by its interaction with the plasma membrane. PMID- 6256063 TI - Amplification of circulating granulocyte-monocyte stem cell numbers following chemotherapy in patients with extensive small cell carcinoma of the lung. AB - Circulating numbers of committed granulocyte-monocyte hematopoietic stem cells (CFUc) were measured in the peripheral blood of 20 patients with extensive-stage small cell lung carcinoma during induction chemotherapy. All patients received cyclophosphamide, doxorubicin, VP16-213, and vincristine. CFUc measurements were made either weekly or twice weekly. As leukocytes declined following chemotherapy, circulating CFUc numbers also declined. However, as leukocytes recovered from their nadir levels, circulating CFUc numbers per mononuclear cell and per ml of whole blood became substantially expanded in 19 and 17, respectively, of the 20 patients studied. Per mononuclear cell, the median CFUc expansion was 7.9-fold, and the highest expansion seen was 157-fold. Per mol of blood, the median CFUc expansion was 6.7-fold, and the highest expansion seen was 46-fold. The magnitude of the amplification, its occurrence in 85 to 95% of patients studied, and its association with leukocyte recovery strongly suggest that appropriately timed collections of peripheral blood mononuclear cells obtained during leukocyte recovery from nonablative chemotherapy could be used to provide hematopoietic stem cells in numbers sufficient to effect hematopoietic reconstitution after subsequent marrow-ablative therapy. PMID- 6256064 TI - Receptor characteristics of the rat mammary carcinoma cell line 64-24. AB - Saturable binding of androgens, glucocorticoids, and triiodothyronine was found in the 64-24 hormone-responsive rat mammary carcinoma cell line. Androgen receptors had a dissociation content (Kd) for methyltrienolone of 3.4 X 10(-10) M and a binding capacity of approximately 10,000 sites/cell in whole cells. 5 alpha [3H]dihydrotestosterone (DHT) was specifically taken up into approximately 2,150 nuclear sites with an affinity of 8.3 X 10(-10) M when nuclei were isolated from whole cells incubated with [3H]DHT. Sucrose gradient centrifugation of cytosol prepared from these cells revealed a displaceable [3H]DHT-binding component which migrated at 8S. Sedimentation analysis with high salt gradients of nuclear extracts from cells incubated with [3H]DHT revealed a peak of radioactivity in the 4S region which was abolished by coincubation of the cells with excess nonradioactive methyltrienolone. Receptors for [3H]dexamethasone were more abundant (approximately 50,000 sites/cell) in whole cells and had a Kd of 7.5 X 10(-9) M, but the number of nuclear binding sites was similar to that for androgens. Specificity studies using unlabeled steroids showed that each of the two classes of steroid receptors had greater affinities for their appropriate hormones. High affinity receptors for estrogens and progestins were not detectable in these cells. Triiodothyronine receptors were demonstrable but at a very low binding capacity (1,100 sites/cell). The Kd of these receptors was 0.6 X 10(-10) M. Cytogenetic studies revealed 44 chromosomes/mitosis with several unique markers. These receptor and karyotypic features suggest that the 64-24 cells may be useful in studying androgen action on breast cancer independently of estrogen or progestin influence, as well as the effects of thyroid hormone and glucocorticoids on breast cancer cells. PMID- 6256065 TI - Activation of sodium cyanate for selective inhibition of protein synthesis in cultured tumor cells. AB - Sodium cyanate, a selective inhibitor of protein synthesis in animal tumors in situ, has no comparable effect when added to tumor cells in culture. However, a rapid inhibition of protein synthesis in cultured tumor cells can be achieved by reaction of cyanate with the drug-metabolizing system of liver microsomes. Procedures are described for the induction, preparation, and testing of an active cytochrome P-450 fraction which converts cyanate to a short-lived dialyzable metabolite that selectively inhibits amino acid incorporation in tumor cells without a corresponding effect on protein synthesis in normal cells. The suppression of tumor protein synthesis is not due to a general toxicity reaction because thymidine incorporation into the DNA of tumor cells is not inhibited by the cyanate metabolite. When HeLa cells are exposed to sodium butyrate, a substance reported to suppress the malignant phenotype in several tumor cell lines, they lose their sensitivity to the cyanate metabolite. Chick fibroblasts which are normally insensitive to the cyanate metabolite become cyanate sensitive after transformation by the Schmidt-Ruppin strain of the Rous sarcoma virus. PMID- 6256066 TI - A mitogenic factor for transformed fibroblasts from human platelets. AB - Human platelets contain discrete glycoproteins that promote the growth of 3T3 (platelet-derived growth factor 1) and SV3T3 (platelet-derived growth factor 2) cells. The factor that promotes the growth of SV3T3 cells is a heat-labile nondialyzable glycoprotein with an isoelectric point of 7.8 to 8.3. PMID- 6256067 TI - Abnormal responses to mid-ultraviolet light of cultured fibroblasts from patients with disorders featuring sunlight sensitivity. PMID- 6256068 TI - Dietary zinc modulation of Moloney sarcoma virus oncogenesis. PMID- 6256069 TI - Cardiac sodium, potassium-adenosine triphosphatase as a possible site of adriamycin-induced cardiotoxicity. AB - Adriamycin ws tested as a possible inhibitor of cardiac sodium-potassium activated adenosine triphosphatase (Na-K-ATPase). At concentrations of 10(-4) M and lower, Adriamycin had no effect upon either ouabain-sensitive (Na-K-ATPase) or ouabain-insensitive adenosine triphosphatase activity in homogenates and microsomal fractions of cardiac tissue from several different species. Adriamycin inhibited adenosine triphosphatase activity at a concentration of 10(-3) M, but this was due to the inhibition of ouabain-insensitive adenosine triphosphatase rather than to inhibition of Na-K-ATPase. Under no condition was an inhibition of Na-K-ATPase activity by Adriamycin observed. These conditions included preincubation of the enzyme with Adriamycin, chelation of Ca2+, addition of reduced nicotinamide adenine dinucleotide phosphate, and variation of buffer and pH. It was concluded that Na-K-ATPase is not a likely site of Adriamycin-induced cardiotoxicity. PMID- 6256070 TI - Parameters distinguishing herpes simplex virus type 2-transformed tumorigenic and nontumorigenic rat cells. PMID- 6256071 TI - 3':5'-stimulation of cyst formation by dibutyryl cyclic adenosine monophosphate in human urinary bladder tumors cultured in vitro. AB - Ten cases of human urinary bladder tumors, varying from histological Grades I to III, were cultured as fragments on a gyratory shaker. Low-grade tumors formed cysts spontaneously, and dibutyryl cyclic adenosine 3':5'-monophosphate stimulated both the number and the size of cysts. Grade III tumors did not form any cysts in culture, and, with light microscopy, dibutyryl cyclic adenosine 3':5'-monophosphate had no visible effect on the fragments. The cells lining the cysts that occurred in the aggregates were characterized by the appearance of zonula occludens on the aspect of the cells facing the culture medium. Two types of cysts were observed: some were lined by a monolayer of cells; and some were lined by a multilayer. In the former, zonula occludens appeared on the aspect facing the culture medium; in the latter, zonula occludens appeared on both the aspect facing the culture medium and that facing the cavities. These specialized structures functioned as tight intercellular junctions as one component of the complex of functions required for effective transport by sheets of epithelium. PMID- 6256072 TI - Prostaglandin E-mediated mitogenic stimulation of mouse epidermis in vivo by divalent cation ionophore A 23187 and by tumor promoter 12-O-tetradecanoylphorbol 13-acetate. AB - When applied to mouse skin in vivo, both the strong tumor promoter 12-O tetradecanoylphorbol-13-acetate (TPA) (2 nmol) and the divalent cation ionophore A 23187 (200 nmol) caused the same responses, i.e., skin inflammation and prostaglandin E2-mediated epidermal hyperplasia. In both cases, these events were accompanied by certain biochemical reactions in the epidermis such as an increase in the biosynthesis of and sensitivity to prostaglandin E2, increase in ornithine decarboxylase and phosphodiesterase activities, and refractoriness of cyclic adenosine 3':5'-monophosphate production to beta-adrenergic stimulation. In contrast to A 23187, TPA did not induce degranulation of mast cells; whereas, in contrast with TPA, A 23187 did not show tumor-promoting activity. These results indicate that the observed biological effects of TPA are no indication of tumor promoting ability and that, on the other hand, the mitogenic effects of A 23187 are possibly not due to its properties as a calcium ionophore. PMID- 6256073 TI - Phase I study of cis-diamminedichloroplatinum(II) administered as a constant 5 day infusion. AB - Thirty patients with metastatic malignancy of various types were treated with cis diamminedichloroplatinum(II) (DDP) administered by continuous infusion for 120 hours. The starting dose was 20 mg/m2/day (100 mg/m2/course) and was escalated by stages to 40 mg/m2/day (200 mg/m2/course). Dose-limiting toxicity was observed at 30 mg/m2/day (150 mg/m2/course), manifested as marrow suppression and particularly thrombocytopenia in 13 of 14 patients evaluated at doses greater than or equal to 30 mg/m2/day. The gastrointestinal toxicity characteristic of bolus treatment schedules was less intense but was cumulative and dose-related. Renal toxic effects developed in five of 30 patients in spite of adequate hydration and daily diuretic therapy. Peripheral neuropathy developed in the only two patients who received four courses of continuous-infusion DDP. Antitumor effects were observed in six patients (oral cancer, two; lymphoma, one; prostatic cancer, one; hepatoma, one; and bronchogenic carcinoma, one). The recommended starting dose for continuous venous infusion therapy with DDP is 30 mg/m2/day for 5 days. PMID- 6256074 TI - Results of whole-brain irradiation for metastases from small cell carcinoma of the lung. AB - Prophylactic brain irradiation significantly reduces the proportion of patients with small cell carcinoma of the lung (SCCL) who develop brain metastases. Therapeutic brain irradiation could be used instead of prophylactic irradiation if it could be delivered promptly after diagnosis of intracranial spread and if it were highly effective. Forty of 188 patients with SCCL seen in the Medical College of Wisconsin Affiliated Hospitals had brain metastases either at initial diagnosis (23 patients) or after treatment (17 patients). Irradiation was administered to the whole brain at doses ranging from 3000 rads in 2 weeks to 4000 rads in 3 weeks. Neurologic function was the same for those patients with initial and delayed metastases and did not correlate with survival. Response to irradiation affected survival. After the diagnosis of brain metastases, survival was the same whether metastases were initially present or were delayed. Eighteen (45%) of the patients died from brain metastases and two (5%) are alive following disease recurrence in the brain. Increasing survival with SCCL due to effective chemotherapy is associated with an increasing failure rate in the brain which may eventually reach the 50% rate found at autopsy. Therapeutic brain irradiation is not sufficiently effective to preclude prophylactic irradiation. PMID- 6256075 TI - Augmentation of vincristine neurotoxicity by irradiation of peripheral nerves. AB - Four cases are presented in which children receiving radiation therapy and combination chemotherapy had unilateral severe and prolonged neurotoxic effects. Augmentation of vincristine neurotoxicity by irradiation of peripheral nerves is suggested. PMID- 6256076 TI - Chemotherapy for small cell bronchogenic carcinoma: CCNU and doxorubicin compared to CCNU, doxorubicin, vincristine, and procarbazine. AB - Forty consecutive patients with small cell bronchogenic carcinoma were treated. The first 18 patients were treated with CCNU and doxorubicin (Adriamycin) (CA). The next 22 patients were treated with CCNU, doxorubicin, procarbazine, and vincristine (CAPO). Patient characteristics were similar. The partial plus complete response rate was 55% (ten of 18 patients) in the CA group compared to 41% (nine of 22 patients) in the CAPO group. The median survival from treatment was 28 weeks in the CA group compared to 33 weeks in the CAPO group. There were no drug-related deaths among the patients receiving CA compared to two definite and three probably drug-related deaths among the patients receiving CAPO. The addition of procarbazine and vincristine to CA for the treatment of small cell bronchogenic carcinoma resulted in increased toxicity and no survival benefit. PMID- 6256077 TI - DNA topoisomerases. PMID- 6256078 TI - Genetic approaches to cyclic AMP effects in cultured mammalian cells. PMID- 6256079 TI - Nucleotide sequence analysis of the long terminal repeat (LTR) of avian retroviruses: structural similarities with transposable elements. AB - The nucleotide sequences of the long terminal repeat (LTR) from six independently derived avian retrovirus recombinant DNA clones have been determined. The LTRs from three clones are approximately 350 bp in length and differ only in minor base insertions or substitutions. Three other clones have smaller LTRs, each with a large deletion which ranged from 89 to 161 bp. Sequence comparisons of the six LTRs indicate that there is conservation of sequences derived from the 5' terminus of viral RNA and extensive divergence of the 3'-specific sequences. The LTR sequences were obtained from clones of unintegrated viral DNA. Comparison of these LTRs with the sequence of an integrated Schmidt-Ruppin D provirus deduced previously reveals that two nucleotides present at the terminus of the LTR of the unintegrated DNA are absent in the integrated provirus. Analysis of the nucleotide sequence of the LTR from one clone, lambda RAV2-2, reveals several putative regulatory sites for the initiation and termination of transcription. There are also several structural features of the LTR which are analogous to procaryotic and eucaryotic transposable elements. These structural analogies include the presence of inverted complementary repeats at the termini of the LTR, deletions adjacent to LTR termini, and sequence homologies with transposable and other genetic elements. These observations suggest that the LTR of retroviruses function in the control of gene expression and integration. PMID- 6256080 TI - Mating signals control expression of mutations resulting from insertion of a transposable repetitive element adjacent to diverse yeast genes. AB - ROAM mutations cause overproduction in S. cerevisiae. Overproduction of ROAM mutant gene products is less in MATa/MAT alpha diploid strains which cannot conjugate than in haplolid strains which can. Overproduction occurs in diploid strains capable of mating whether or not they are capable of sporulating. Overproduction decreases when haploid ROAM mutants also contain the ste7 mutation which prevents conjugation; other ste mutations do not affect the expression of ROAM mutations. Cloning of the ROAM mutant gene CYC7-H2 shows that a 5.5 kb sequence homologous to a transposable and reiterated Ty1 element is inserted in the 5' noncoding region of the CYC7 structural locus. The similar genetic properties of other ROAM mutations suggest that they each contain an inserted Ty element. These results also suggest that ROAM mutations respond to signals normally directed toward genes controlling conjugation functions, and that sequences present in Ty elements may be adjacent to structural loci and are the normal receptors for these signals. PMID- 6256081 TI - Unwinding and rewinding of DNA by the RecBC enzyme. AB - Under physiological conditions the initial action of the RecBC enzyme (exonuclease V) on duplex DNA is unwinding of the DNA strands. We have examined by electron microscopy the initial products of this unwinding reaction. When such reactions are carried out in the presence of DNA binding protein, unwinding structures are seen both at the terminus of the duplex DNA and at locations remote from the ends of the DNA molecule. Both terminal and internal unwinding structures proceed along DNA at about 300 nucleotides per second, and the single stranded loops in both types of structure enlarge at about 100 nucleotides per second. In the internal unwindings DNA must be rewound behind the enzyme at about 200 nucleotides per second. The structures do not occur on supercoiled or nicked circular DNA, indicating that free ends are needed for their formation. In the absence of DNA binding protein only internal unwinding structures are seen, suggesting that the internal structures are formed from the terminal unwindings by base-pairing of their unwound single-strand tails. We present a model which incorporates these structures and is consistent with previous observations on the unwinding and degradative actions of the enzyme. In this model the enzyme travels through duplex DNA by unwinding the DNA ahead of itself and rewinding it behind itself. The internal unwindings produced by the RecBC enzyme could be active in initial synapsis step in genetic recombination. PMID- 6256082 TI - High efficiency transformation by direct microinjection of DNA into cultured mammalian cells. AB - Direct microinjection of DNA by glass micropipettes was used to introduce the Herpes simplex virus thymidine kinase gene into cultured mammalian cells. When DNA was delivered directly into the nuclei of LMTK-, a mouse cell line deficient in thymidine kinase activity, 50--100% of the cells expressed TK enzymatic activity. In contrast, no TK activity could be detected when the DNA was injected into the cytoplasm. The number of injected LMTK- cells capable of indefinite growth in a TK+ selective medium (that is, transformants) depended on the nature of the plasmid DNA into which the HSV-TK gene was inserted. One cell in 500-1000 cells which received nuclear injections with pBR322/TK DNA gave rise to a viable colony when grown in HAT medium (that is, a TK+ selective medium). The transformation frequency increased to one in five injected cells when specific SV40 DNA sequences were also introduced into the HSV-TK plasmid. With the microinjection procedure transformation frequency was relatively insensitive to DNA concentration and did not depend on co-injecting with a carrier DNA. Most of the transformants were stable in nonselective medium as soon as they could be tested. PMID- 6256083 TI - Changes in polypeptide pattern in ASV-transformed rat cells are correlated with the degree of morphological transformation. AB - Normal rat kidney cells (NRK) have been transformed with an avian sarcoma virus (ASV) mutant that induces a temperature-sensitive transformed phenotype. When compared in vitro different ASV-transformed clones showed different degrees of morphological transformation at the permissive temperature, while they all reverted to normal at 39 degrees C. Comparisons of the polypeptide patterns of the different cells showed two things. First, a group of about 30 polypeptides, amounting to 5% of all the polypeptides analyzed in normal cells, were affected in all ASV-transformed clones and also in two papovavirus-transformed clones and also in two papovavirus-transformed NRK clones. Second, the patterns were found to differ between the clones in that varying numbers of polypeptides were found to be affected depending on the clone; the number of polypeptide changes showed a good correlation with the degree of morphological transformation. At the nonpermissive temperature the polypeptide patterns of ts ASV-transformed cells were indistinguishable from that of the untransformed cells, which is in agreement with the morphological data. PMID- 6256084 TI - Amplification and rearrangement of integrated SV40 DNA sequences accompany the selection of anchorage-independent transformed mouse cells. AB - Clones of SV40 tsA mutant-transformed mouse embryo cells with a temperature independent transformed growth phenotype were derived from a parental line with a temperature-dependent growth phenotype, using the selective pressure of anchorage independent growth in agar at 40 degrees C. The parental J78 clone contained a complex tandem structure of integrated SV40 DNA within two cellular DNA fragments of 10 and 14 kb, generated by Bgl II digestion. The new clonal derivatives, in addition to an altered growth phenotype, displayed additional high molecular weight sites of SV40 DNA integration. A marked structural similarity among integration sites suggested that the new sites may have arisen by duplication and translocation of an original integration structure, or via an unequal crossover event. The rearrangement of viral DNA sequences appears to be specifically associated with the emergence of temperature-independent clones, since the isolation of new clones under nonselective conditions, that is, growth in semi solid medium at 33 degrees C, was not accompanied by modification in cellular sequences containing SV40 DNA. PMID- 6256085 TI - The white pock (mu) mutants of rabbit poxvirus. III. Terminal DNA sequence duplication and transposition in rabbit poxvirus. AB - The restriction fragment patterns of the DNA of three white pock (mu) nonhost range mutants RPmu mutants) of rabbit poxvirus (RPV) show the presence of net insertions of DNA. Two of the mutants (RPmu21 and RPmu7) contain two molar quantities of 13 X 10(6) and 15 X 10(6) daltons, respectively, of the left-most viral DNA sequences. The extra copy of these sequences was inserted into the right-most region of the viral genome which in both cases had been modified by deletion of 10 X 10(6) daltons of the original extreme right-most DNA sequences. Hence two mutants with "left-hand" mirror image termini of 13 X 10(6) and 15 X 10(6) daltons of DNA were generated with an overall net increase in mass of 3 X 10(6) and 5 X 10(6) daltons of DNA to yield genome molecular weights of 121 X 10(6) and 123 X 10(6) for RPmu21 and 7, respectively. A third mutant (RPmu81g) contained 28 X 10(6) daltons of the right-most parental DNA sequences inserted into the left end of the genome, which had deleted 6 X 10(6) daltons of the extreme left-hand sequences. This variant contains "right-hand" mirror image termini of 28 X 10(6) daltons of DNA and a net increase in molecular weight of 22 X 10(6) daltons of DNA to yield a genome molecular weight of 140 X 10(6). The cross-linked end of the transposed sequences is retained in all cases. Our data suggest that the terminal DNA sequences at either end of the virus are not essential for a productive infection in certain host cells and that the pathogenicity of orthopoxviruses may be related in part to a series of varied and interchangeable DNA sequences located at both extremes of a high conserved genome core. PMID- 6256086 TI - Epidermal growth factor-toxin A chain conjugates: EGF-ricin A is a potent toxin while EGF-diphtheria fragment A is nontoxic. AB - We have prepared a 2-pyridyl-dithiopropionate derivative of epidermal growth factor (EGF) and conjugated the derivative by disulfide interchange to the A chain of ricin (RTA) or to fragment A of diphtheria toxin (DTA). The EGF-RTA conjugate was toxic to 3T3 cells at concentrations (10(-9)--10(-11) M) similar to those at which EGF exerts its biological activity and within an order of magnitude of the toxicity of ricin. Ricin A chain alone only exerted toxic effects at concentrations (10(-6)--10(-7) M) three to four orders of magnitude higher than required for the activity of the EGF-RTA conjugate or ricin. An unconjugated mixture of RTA and EGF had no greater effect than RTA alone. Toxicity of the EGF-RTA conjugate on 3T3 cells was competed by EGF and was blocked by antibodies to RTA, but not by lactose or antibodies to the ricin B chain (RTB). In contrast to the EGF-RTA conjugate, the EGF-DTA conjugate proved virtually nontoxic at concentrations as high as 3 X 10(-8) M. Control experiments showed that the EGF-DTA conjugate retained EGF receptor binding activity; the DTA moiety of the hybrid retained ADP-ribosyltransferase activity; and the disulfide bridge linking DTA to EGF was readily reducible. PMID- 6256087 TI - Nerve growth factor mediates phosphorylation of specific proteins. AB - Nerve growth factor (NGF), epidermal growth factor (EGF), insulin, cholera toxin (CT) and cAMP all stimulate the phosphorylation of proteins in the PC12 nerve like cell line. NGF, CT and cAMP enhance phosphorylation of the same set of proteins including tyrosine hydroxylase, ribosomal protein S6, histones H1 and H3, and the nonhistone chromosomal and cytoplasmic high mobility group (HMG) 17 protein, and reduce phosphorylation of H2A. EGF but not insulin enhances the phosphorylation of tyrosine hydroxylase. Insulin but not EGF enhances the phosphorylation of histone H3 and decreases the phosphorylation of H2A. EGFD and insulin each enhance phosphorylations of both ribosomal protein S6 and histone H1, but neither hormone induces phosphorylation of HMG 17. The extent of these effects depends upon the ligand concentration and is half-maximal at physiological concentrations of the hormones (beta-NGF, 2 ng/ml; EGF, 1 ng/ml. insulin, 0.5 microunits/ml). Maximal effects of NGF are seen within 15 min and persist even after 3 days of culture in the presence of NGF. When phosphorylation of ribosomal protein S6 is maximally stimulated by NGF, no further stimulation can be achieved by adding saturating quantities of either cAMP or CT. However, simultaneous addition of saturating quantities of NGF and either EGF or insulin results in an enhancement of phosphorylation that is equal to the sum of that achieved when the two ligands are added separately. These results suggest that the enhanced phosphorylation of S6 achieved by NGF or cAMP occurs through a common mechanism which differs from those which mediate EGF or insulin-enhanced phosphorylation. The data also provide strong evidence that the action of NGF included protein phosphorylation mediated by cAMP-dependent protein kinase. The phosphorylation of each of these proteins in response to NGF may play an important role in NGF action. PMID- 6256088 TI - Hypersensitivity of platelets to thrombin: formation of stable thrombin-receptor complexes and the role of shape change. AB - The rate of rat platelet shape change increases sigmoidally with respect to thrombin concentration under conditions where free Ca++ and ADP are limited to prevent platelet aggregation. In addition, the rate of shape change due to thrombin is considerably enhanced when the platelets are first treated with concanavalin A (Con A), an agent which itself produces shape change. In the presence of both agents the rate is considerably greater than the sum of the rates due to Con A and thrombin separately. This suggests that shape change itself may trigger increased platelet sensitivity to thrombin. One possible mechanism through which this might occur is that shape change promotes binding of thrombin to its surface receptors. If so, then Con A-induced shape change might facilitate binding of 125I-thrombin. Initial binding studies using previously described methods showed that nonspecific trapping of 125I-thrombin, which is bound specifically to platelets during shape change, prevents accurate measurements of thrombin binding. We found, however, that a portion of 125I thrombin which is bound specifically to platelets forms a stable complex with a 40,000 dalton platelet protein. This complex cannot be disrupted by boiling in SDS buffer containing 2-mercaptoethanol. Linkage of 125I-thrombin to this protein is specific for thrombin, since it can be competed for by an excess of unlabeled thrombin and because a similar complex does not form using 125I-trypsin. Concentrations of Con A that induce platelet shape change also markedly increase the amount of complex produced by a given thrombin concentration. In addition, colchicine, an inhibitor of Con A-induced platelet function, markedly inhibits formation of the 125I-thrombin-receptor complex. We suggest that the sigmoidal response to thrombin might be related to appearance of new thrombin receptors on the platelet surface. PMID- 6256089 TI - [Antineoplasm immunity testing in health workers at the ORL department of the Postgraduate Medical Institute]. PMID- 6256091 TI - In vivo metabolism of 11-hydroxy-delta-tetrahydrocannabinol to two carboxylic acids and the effects of SKF 525-A, cobaltous chloride and phenobarbital on their formation in rats. PMID- 6256090 TI - Physiological activity of streptothricin antibiotics. PMID- 6256092 TI - Preparation and spectroscopic characterization of molecular species of brain phosphatidylserines. AB - This study describes the first preparation and spectroscopic characterization of naturally occurring phospholipids separated according to degree of unsaturation. Phosphatidylserines (PS) have been prepared from bovine brain and shown to be pure by extensive thin layer chromatographic analysis as well as by infrared spectroscopy and fatty acid analysis. The PS has been separated according to degree of unsaturation and prepared using AgNO3-impregnated silica gel H thin layer chromatography. Fatty acid analysis of the two principal PS subfractions indicates that they are enriched in the molecular species 1-octadecanoyl-2 docosahexaenoyl-sn-glycero-3-phosphorylserine and 1-octadecanoyl-2-octadecenoyl sn-glycero-3-phosphorylserine. The identity of the two PS subfractions was further verified by rechromatographing on several thin layer systems and by infrared spectroscopy. With the use of a 100 MHz Fourier transform nuclear magnetic resonance (NMR) spectrometer, the spectra of bovine whole brain, white matter, gray matter, monoenoic, and hexaenoic PS were obtained. Distinct proton resonances were assigned to double bond protons, protons adjacent to a double bond, and protons between two double bonds, using fatty acid methyl ester standards. The various PS preparations gave different intensities of the various proton resonances which correlated with differences in fatty acid composition. The method provides a convenient, non-destructive spectroscopic method for distinguishing monoenoic and polyunsaturated species of intact phospholipids. Electron spin resonance studies of nitroxide-labelled cholestane in sonicated PS vesicles showed greater probe motion as the unsaturation of the acyl chains was increased. The hexaenoic PS vesicles were more fluid than monoenoic PS vesicles at all temperatures in the range 10-55 degrees C. These results suggest that neuronal membranes are more fluid than myelin membranes as neuronal membranes contain more hexaenoic phospholipids. PMID- 6256093 TI - [Glomus caroticum tumors (apropos of a case)]. AB - An analysis of the current status of carotid body tumors (chemodectomas) including the report of one additional case is presented. Comments are made regarding the clinical recognition and treatment of chemodectomas in general. Historical, anatomic, physiologic and pathologic features are emphasized. PMID- 6256094 TI - [A case of Wilm's tumor in an adult (author's transl)]. PMID- 6256095 TI - [Simultaneous and independent multifocal neoplasms of the large intestine]. AB - The Authors report the presence of two simultaneous neoplasms of the large bowel which are independent of each other from the histological point of view. The Authors point out the more interesting aspects of this particular neoplastic pathology, which creates different clinical syndromes; diagnosis and therapeutic possibilities were investigated. The frequency of these neoplasms is not exceptional, and, therefore, the possible existence even in subjects having a single tumor of the colon or rectum should not be neglected. PMID- 6256096 TI - Steroid hormones and cancer. PMID- 6256097 TI - Urinary excretion of material with beta-endorphin immunoreactivity. PMID- 6256098 TI - Erythrocyte transketolase activity in uremia. AB - We performed a study concerning the activity of erythrocyte transketolase and thiamine metabolism in 73 uremic patients with or without neuropathy and 67 normal control subjects. Although the total vitamin B1 level in whole blood was high in the uremic patients, the transketolase activity in the hemolysate and the thiamine pyrophosphate effect on it were lower than those of normal subjects. The values of the transketolase activity of the two groups were statistically correlated with the levels of the thiamine pyrophosphate effect and the vitamin B1 content of the blood. Inhibition of transketolase activity was apparent in the uremic patients. However, this inhibition did not seem to be the only cause for the development of uremic neuropathy since no significant difference in these activities was observed among uremic patients with and without neuropathy. Moreover, a direct correlation could not be confirmed between transketolase activity and motor nerve conduction velocity. PMID- 6256099 TI - Studies of selected enzymes of phospholipid metabolism in the dystrophic human muscle. AB - Proceeding from deviations of the phospholipid pattern in the muscle in progressive muscular dystrophy, the activities of a number of enzymes of phospholipid metabolism in the normal and dystrophic human muscle were measured. Twelve cases of the Duchenne type and four of the Becker-Kiener type were studied. The activities of CDP-choline:diglyceride-P-cholinetransferase, of CDP choline:ceramide-P-cholinetransferase and of phosphatidylcholine degradation were determined in normal and dystrophic human muscle. A significant difference in enzyme activities between normal and dystrophic muscle could not be established. The activities of a phosphatidylethanolaminemethyltransferase and a transfer of P choline directly from phosphatidylcholine to sphingomyelin could be excluded for normal human muscle. The significance of these results for the integration of phospholipid findings in ideas about pathogenesis of progressive muscular dystrophy is discussed. PMID- 6256100 TI - Electrophoretic and kinetic studies of human erythrocytes deficient in pyrimidine 5'-nucleotidase. AB - A new variant of hereditary hemolytic anemia due to erythrocyte pyrimidine 5' nucleotidase deficiency was found in Japan. Biochemical parameters such as the Michaelis constant, thermostability, electrophoresis and pH curve were studied. The variant showed a high Michaelis constant for cytidine 5'-monophosphate, no thermolability, slower electrophoretic mobility and abnormal optimum pH. The results strongly suggest that the mechanism of this enzyme deficiency is due to a structural gene mutation. PMID- 6256101 TI - Tissue levels of glycolytic enzymes in phosphoglycerate kinase deficiency. AB - Phosphoglycerate kinase deficiency is a rate, X-linked disorder associated with a severe haemolytic anaemia. In general the deficiency has been demonstrated only in erythrocytes and leucocytes. However, in a subject with this condition, the activity of phosphoglycerate kinase in lymphocytes and platelets was also shown to be less than 5% of the normal value. Following the death of this subject in 1979, the deficiency was also found to occur in tissue samples of brain, skeletal muscle, liver and cardiac muscle, obtained at the autopsy. Values for phosphoglycerate kinase were of the order of 0.5-5% of normal controls. Other glycolytic enzymes which were tested were hexokinase, pyruvate kinase, enolase and 2-phosphoglyceromutase. In general, values for these enzymes were either normal or slightly raised. PMID- 6256102 TI - [The examination for radioimmunoassay cyclic nucleotide kit of Hoechst (author's transl)]. PMID- 6256103 TI - ACTH hypertension modifies the haemodynamic effects of prostacyclin infusions in sheep. AB - 1. The haemodynamic effects of short-term prostacyclin infusions (0.05-0.50 microgram/kg per min) were investigated in conscious adult sheep. 2. Haemodynamic dose-response curves to prostacyclin were performed before, during and after production of ACTH-induced hypertension. 3. Prior to ACTH administration prostacyclin produced dose-dependent reductions in mean arterial pressure, total peripheral resistance and stroke volume and these were accompanied by increased in heart rate and cardiac output. 4. After 5 days of ACTH-induced hypertension prostacyclin produced similar effects on mean arterial pressure to those seen prior to ACTH but the effects on heart rate, cardiac output, stroke volume and total peripheral resistance were markedly increased. 5. These studies demonstrate that the responsiveness of the circulation to prostacyclin is altered in ACTH induced hypertension. PMID- 6256104 TI - Renal, adrenal and vascular changes during inhibition of converting enzyme with captopril. AB - 1. In rats treated continuously with captopril (80 microgram/h, i.p.), for 2 days, blood pressure decreased and adrenal angiotensin II receptor concentration was decreased from 160 fmol/mg protein (s.e.m. = 9) in controls to 131 fmol/mg protein (s.e.m. 7, P < 0.01, n = 10). However, after 5 days of continuous treatment, blood pressure had returned to normal and adrenal receptor concentrations in treated rats were not significantly different from controls (180 fnol/mg, s.e.m. = 11 and 203 fmol/mg protein s.e.m. = 14 respectively, 0.1 > P > 0.05). 2. Vascular reactivity, defined as the pressor response to exogenous angiotensin II, increased concurrently by 166 and 33% respectively. 3. In anaesthetized dogs (n = 8), captopril (1.5 mg/kg, i.v.) caused a fall in blood pressure, and uring bradykinin excretion increased from 1-08 (s.e.m. = 0.14) to 1.64 microgram/h (s.e.m. = 0.33, P < 0.025) at 15 min. Renal blood flow increased significantly (P < 0.01) with no change in glomerular filtration rate, and there was no change in either renal venous or arterial blood bradykinin levels. 4. Thus, converting enzyme inhibition produces transient secondary changes in angiotensin receptors and vascular reactivity. Increased urine bradykinin probably reflects decreased catabolism of intrarenal bradykinin. The hypotensive effect of captopril may be due in part to raised levels of bradykinin in the kidney. PMID- 6256105 TI - Angiotensin converting enzyme in the brain of spontaneously hypertensive rats. AB - 1. Angiotensin converting enzyme (ACE) was measured in homogenates of regions of rat brain using the substrate Hip-His-Leu. 2. The enzyme resembles classical ACE in its marked Cl- dependence and inhibition by both SQ 20,881 (24 micro mol/1) and EDTA (1 mmol/1). 3. Spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto controls (NT-WK) were killed at 20-22 weeks of age their brains dissected into eight regions. 4. There were marked region variations of ACE with highest levels in striatum, hippocampus, cerebellum and pituitary and lower levels in hypothalamus and cerebral cortex. 5. In three brain regions ACE was significantly lower in SHR compared to NT-WK: medulla oblongata (P < 0.05), hypothalamus (P < 0.02) and cerebral cortex (P < 0.05). In the other sites the levels were not different. 6. These region-specific differences of ACE in the SHR could lead to altered production or metabolism of central neuropeptides postulated to be involved in the control of blood pressure. PMID- 6256106 TI - Effect of ACTH administration on the haemodynamic response to arginine vasopressin in sheep. AB - 1. Blood pressure, heart rate and cardiac output were studies in intace conscious sheep during AVP infusion at 0.1, 0.25, 0.5 and 1.0 microgram/min for 30 minutes to determine whether pressor responsiveness to AVP was altered in ACTH-induced hypertension. 2. Prior to ACTH treatment, AVP produced rises in blood pressure associated with a fall in heart rate and cardiac output. 3. During ACTH treatment, pressor responsiveness to AVP and decrease in cardiac output were unchanged, but reflex bradycardia was reduced. 4. ACTH-induced hypertension in sheep is not associated with enhanced pressor responsiveness to AVP. PMID- 6256107 TI - Haemodynamic changes in ACTH-incuded hypertension in sheep. AB - 1. ACTH (20 microgram/kg per day) produced an elevation in blood pressure associated with an increase in cardiac output in conscious sheep, due in the first 72 h to a rise in heart rate. Stroke volume did not rise until the fourth day of ACTH treatment. 2. Calculated total peripheral resistance did not change. 3. Intreavenous administration of acebutolol prior to and during ACTH administration did not modify the rise in blood pressure, but this was associated with a rise in total peripheral resistance. 4. These studies show that while ACTH induced hypertension is usually associated with increased cardiac output, rather than total peripheral resistance it still occurs, but is associated with a rise in total peripheral resistance if the rise in cardiac output is prevented by beta adrenoreceptor blockade. PMID- 6256108 TI - Ultrasonic stimulation of low lumbar nerve roots as a diagnostic procedure: a preliminary report. AB - Ultrasonation of irritated lumbosacral nerve roots produces radiation of pain into the ipsilateral buttock. If pain is reported when using the ultrasonic stimulator with no sonation, good evidence is obtained that the patient's symptoms are not arising from radicular pathology. PMID- 6256109 TI - Increase in prostaglandins during converting enzyme inhibition. AB - 1. Because changes in the plasma concentration of angiotensin II and bradykinin appear inadequate to account completely for the hypotensive response to captopril, we measured changes in plasma prostaglandins in response to increasing doses of captopril in nine supine normal male subjects studied on both a high (200 mol/l) and low (10 mol/l) sodium intake. 2. On both the high and low sodium diets, captopril induced significant (P < 0.01) increments in the 13,14-dihydro 15-keto metabolite of the vasodilatory prostaglandin E2, which correlated significantly with the fall in blood pressure (P < 0.0001). 3. No significant changes were noted in the plasma levels of 6-keto-prostaglandins F1 alpha or thromboxane B2, the stable products of prostacyclin and thromboxane A2 respectively. PMID- 6256110 TI - Altered cardiac beta-adrenoreceptors in spontaneously hypertensive rats receiving salt excess. AB - 1. Altered adrenergic responsiveness of hearts and blood vessels occurs in both experimental and clinical hypertension. 2. Since salt excess aggravates both types of hypertension, we investigated beta-adrenoreceptor properties in the hearts of spontaneously hypertensive and normotensive rats drinking 1% NaCl or tap water for 3 weeks. 3. Sodium loading increased heart weight in both spontaneously hypertensive and normotensive rats. 4. In spontaneously hypertensive rats excess salt attenuated the age-related decrease in beta adrenoreceptor number observed in spontaneously hypertensive and normotensive rats drinking tap water and in normotensive rats drinking 1% NaCl. 5. Unlike the normotensive rats, which did not show a relationship between beta-adrenoreceptor number and blood pressure, spontaneously hypertensive rats on tap water and 1% NaCl showed a significant negative logarithmic relationship between these two variables. These data provide further evidence implicating sodium excess as an aggravating factor in this model of experimental hypertension. PMID- 6256111 TI - Effects of variations in sodium intake on the acute vasodepressor response to kininase II inhibition in rats with mild two-kidney, one-clip hypertension. AB - 1. Unilateral renal artery constriction in rats maintained on a sodium-deplete, but not sodium-replete, diet induced an augmented acute vasodepressor response to kininase II inhibition produced by an intravenous injection of the dipeptidyl carboxypeptidase inhibitor captopril (250 microgram) during continuous saralasin induced angiotensin II blockade (10 microgram/min). Dietary sodium restriction alone in sham-operated rats had no effect. 2. Acute bilateral adrenalectomy (18 24 h) did not preclude the demonstration of an augmented response to kininase II inhibition in sodium-depleted rats with benign two-kidney, one-clip hypertension. Neither did chronic administration of deoxycorticosterone acetate in intact rats elicit an augmented response. 3. The augmented acute vasodepressor response to kininase II inhibition in sodium-depleted rats with benign two-kidney, one-clip hypertension is probably due to bradykinin potentiation and secondary to an increased activity of the kallikrein-kinin system. The mechanism responsible for this apparent increase is not known, but neither hyperangiotensinemia nor hyperaldosteronism seems to play a role. PMID- 6256112 TI - Sodium-potassium-dependent ATPase activity in erythrocyte ghosts of patients with primary and secondary hypertension. AB - 1. We have investigated the function of the Na+-K+ pump in the erythrocytes of patients with various types of hypertension by measuring the activity of ouabain sensitive Na+-K+-dependent ATPase and ouabain-insensitive ATPase in the erythrocyte ghosts of these patients. 2. Mean Na+-K+-ATPase activity was increased threefold in six patients with Cushing's syndrome and hypertension (0.985 +/- SD 0.288 mumol of phosphate h-1 mg-1) compared with that in 49 control subjects (0.334 +/- 0.147 mumol of phosphate h-1 mg-1) (P < 0.0025), but not in four patients with primary aldosteronism (0.278 +/- 0.108 mumol of phosphate h-1 mg-1). 3. Na+-K+-ATPase activity slightly exceeded the control range in 57 patients with primary hypertension (0.410 +/- 0.245 mumol of phosphate h-1 mg-1; P < 0.025) and in 12 patients with renal hypertension (0.475 +/- 0.250 mumol of phosphate h-1 mg-1) (P < 0.025). 4. There was no difference in ouabain insensitive ATPase between the controls and the different types of hypertension. 5. The data support the hypothesis of an activation of the Na+ pump in patients with glucocorticoid excess. This helps to explain previous observations of a redistribution of sodium and water to the extracellular compartment in experimental glucocorticoid-induced hypertension. PMID- 6256113 TI - Studies on the role of sodium-potassium-activated ATPase as determinant of vascular reactivity in Wistar-Kyoto and spontaneously hypertensive rats. AB - 1. The role of Na+-K+-activated ATPase in the regulation of resistance vessel reactivity to barium chloride and noradrenaline was investigated with a pair perfused hindquarter technique in spontaneously hypertensive rats and Wistar Kyoto rats (6 and 12 week old). Ouabain (10(-4) mol/l) was used to inhibit the sodium pump. 2. In all groups studied, dose-response curves to agonists were shifted to the left when ouabain was added to the perfusion medium. This potentiation in vascular reactivity produced by ouabain was expressed as 'index for sodium-pump inhibition' (ISPI = ED 50 of an agonist/ED50 + ouabain). 3. In mature rats index for sodium-pump inhibition calculated for both agonists was significantly greater in spontaneously hypertensive rats in comparison with Wistar-Kyoto rats, but not so in young spontaneously hypertensive rats. There was, however, a trend towards increased noradrenaline sensitivity in spontaneously hypertensive rats although the difference from Wistar-Kyoto rats was not statistically significant. 4. The data may suggest that there is some increase in the activity of the sodium pump in the resistance vessels of mature spontaneously hypertensive rats, perhaps to compensate for an increased passive sodium permeability. PMID- 6256114 TI - Effect of sodium-potassium-dependent ATPase inhibition on noradrenaline-activated calcium sensitivity of mesenteric resistance vessels in adult spontaneously hypertensive rats. AB - 1. We have investigated the noradrenaline-activated calcium sensitivity of 150 micrometer mesenteric resistance blood vessels from spontaneously hypertensive and control Wistar-Kyoto rats. 2. Under control conditions the spontaneously hypertensive rat blood vessels had a greater calcium sensitivity than the Wistar Kyoto rat vessels. 3. In the presence of 1 mmol of ouabain/l, a treatment known to inhibit the sodium-potassium-dependent ATPase, the responses of the spontaneously hypertensive rat blood vessels were reduced more than those of the Wistar-Kyoto rat blood vessels, so that the responses of spontaneously hypertensive rat and Wistar-Kyoto rat blood vessels were then similar. 4. Similar results were obtained by removing external potassium, a procedure which should also inhibit the sodium-potassium-ATPase. 5. The results suggest that the greater noradrenaline-activated calcium sensitivity of spontaneously hypertensive rat blood vessels may be associated with an increased sodium-potassium-ATPase activity. PMID- 6256115 TI - Increased adrenaline, beta-adrenoreceptor stimulation and phospholipid methylation in pineal gland of spontaneously hypertensive rats. AB - 1. In pineal glands of adult spontaneously hypertensive rats (Okamoto strain), dopamine levels increased 34%, adrenaline concentrations increased 152% and noradrenaline levels decreased by 26%, when compared with Wistar-Kyoto normotensive controls. 2. These results are consistent with the hypothesis of an increased uptake of peripheral adrenaline resulting in increased release of noradrenaline from pineal sympathetic nerves in hypertensive rats. 3. The activity of pineal N-acetyltransferase was increased fourfold in hypertensive rats, indicating increased stimulation of pineal beta-adrenoreceptors. 4. Methylation of pineal membrane phospholipids was also increased (100-320%) in hypertensive rats. 5. These results indicate a correlation in vivo between increased beta-adrenoreceptor stimulation and increased methylation of membrane phospholipids in the rat pineal gland, which could result in changes in membrane fluidity and affect the coupling of the beta-adrenoreceptors to the adenylate cyclase. PMID- 6256116 TI - Cyclic AMP generation in hypothalamus of hypertension-prone and -resistant rats. AB - 1. This noradrenaline-induced accumulation of cyclic AMP is decreased in both the anterior and the posterior hypothalamus of hypertension-prone as compared with resistant rats, but is similar in the cortex. 2. The noradrenaline-induced accumulation of cyclic AMP is decreased in the posterior hypothalamus as compared with the anterior hypothalamus of both strains. 3. The decreased sensitivity to phosphodiesterase inhibitor in the hypothalamus of hypertension-prone as compared with resistant rats suggests that strain differences in phosphodiesterase activity may exist. 4. Since differences in cyclic AMP were found in the hypothalamus and the medulla oblongata, regions involved in blood pressure control, but not in the cortex, they may be relevant to the diverse susceptibility to hypertension of hypertension-prone and resistant rats. PMID- 6256117 TI - Effects of tonin on vascular smooth muscle of the hypertensive rat and normal rabbit. AB - 1. The response of arterial smooth muscle to noradrenaline was studied in one clip hypertensive rats with or without the contralateral/kidney and in normotensive rabbits. 2. Strips of aorta from one-kidney, one-clip hypertensive animals were less responsive to noradrenaline than normotensive control rats. The contractile response of strips from two-kidney, one-clip hypertensive animals was not different from the control group. These results suggest that the mechanisms responsible for the lesser reactivity in the one-kidney hypertensive group are not a consequence of elevated blood pressure itself, but may be related to the intrinsic contractility of aortic smooth muscle. 3. Tonin potentiated the contraction induced by noradrenaline in aortic strips from hypertensive and normotensive rats. However, this effect was more important in the one-kidney, one clip hypertensive animals. In the aortic and mesenteric strips from normal rabbits, tonin produced not only potentiation to noradrenaline but direct contraction. 4. The potentiation to noradrenaline and the direct effect of tonin were not affected by a variety of antagonists but were blocked by a calcium ion antagonist, verapamil, suggesting that tonin may act directly on vascular smooth muscle through mechanisms which might be mediated by calcium ions. PMID- 6256118 TI - Haemodynamic effects of increasing extracellular potassium concentration in ACTH induced hypertension in sheep. AB - 1. ACTH administration (20 microgram day-1 kg-1) to sheep produces hypertension associated with a raised cardiac output and hypokalaemia. 2. The aim of the present experiments was to detail the haemodynamic changes associated with restoration of the extracellular potassium concentration in sheep with ACTH induced hypertension. 3. After 7 days of ACTH treatment potassium chloride (10 mmol/h) was infused for 3 days to restore plasma [K+] to the pre-ACTH value. 4. ACTH reduced plasma [K+] from 4.4 +/- 0.1 to 3.2 +/- 0.2 mmol/l but 3 days of potassium chloride infusion returned plasma [K+] to 4.3 +/- 0.2 mmol/l. 5. ACTH increased mean arterial pressure from 67 +/- 2 to 88 +/- 1 mmHg in the first 7 days and it remained elevated during potassium chloride infusion (91 +/- 5 mmHg on day 10). 6. Cardiac output rose with 7 days ACTH treatment from 4.9 +/- 0.2 to 6.0 +/- 0.6 l/min but fell progressively with potassium chloride infusion to 4.9 +/- 0.3 l/min on day 10. 7. These studies suggest that potassium status or extracellular [K+] may play a role in determining the haemodynamic profile associated with steroid-induced hypertension. PMID- 6256120 TI - Converting enzyme inhibition during chronic angiotensin II infusion in rats: evidence against a non-angiotensin mechanism. AB - 1. To investigate the non-angiotensin effects of converting enzyme inhibition, angiotensin II was infused intravenously at 30 ng/min for 9 days in conscious rats to produce moderate blood pressure elevation. One group was given captopril (SQ 14 225) by gavage (100 mg/kg twice daily) and the other glucose. 2. After 7 days of captopril administration, enzyme blockade was confirmed by a tenfold greater depressor sensitivity to exogenous bradykinin and a markedly decreased plasma angiotensin converting enzyme activity. 3. Mean arterial pressure, heart rate and plasma renin activity were not different between captopril and glucose treated groups in the presence of angiotensin II. Metabolic studies also revealed no long-term differences in water and food intake, weight change or sodium and potassium metabolism. 4. These findings suggest that, in the presence of angiotensin II, there is no detectable haemodynamic or metabolic effect of converting enzyme inhibition in rats and, therefore, that bradykinin plays little or no role in its long-term antihypertensive action. PMID- 6256119 TI - Adrenal angiotensin II receptors and vascular reactivity to angiotensin II in the rat during continuous inhibition of angiotensin converting enzyme. AB - 1. The effect of continuous infusion of captopril (80 microgram/h) for up to 5 days on blood pressure, adrenal angiotensin II receptors and vascular reactivity exogenous angiotensin II, arginine vasopressin and noradrenaline was studied in the rat. 2. In treated rats, blood pressure decreased transiently to a minimum after 2 days (-18 mmHg). Vascular reactivity to angiotensin II, but not to arginine vasopressin, was also increased significantly after 2 days, but vascular reactivity to noradrenaline decreased. After 5 days, vascular reactivity to angiotensin II had returned to normal and was similar to that of sham-treated controls. Adrenal angiotensin II receptor concentrations decreased significantly after 1 and 2 days, but at 5 days were again similar to controls There was no change in receptor affinity. 3. Converting enzyme inhibition with captopril causes transient specific changes in adrenal angiotensin II receptors and vascular reactivity. The receptor and vascular effects may facilitate and oppose, respectively, the early changes in blood pressure with captopril, but a long-term contribution from either is unlikely. PMID- 6256122 TI - [The use of sequence 1-39 human synthetic ACTH in therapy of asthmatic syndromes]. PMID- 6256121 TI - Effects of beta-lipotropin on aldosterone production in rats. AB - 1. beta-Lipotropin has a potent aldosterone stimulating effect in vitro and in vivo in rats. 2. The maximum aldosterone response to beta-lipotropin was the same as to ACTH and greater than to angiotensin II. 3. Although doses of ACTH which maximally stimulated aldosterone significantly increased cyclic AMP production, maximally stimulating doses of sheep beta-lipotropin did not increase cyclic AMP production significantly. 4. These data suggest that beta-lipotropin may play a role in aldosterone regulation through a mechanism different from that of ACTH. PMID- 6256123 TI - Collagen-bound collagenase. AB - The presence of collagenase bound to collagen extracted and purified from several animal and human sources by a standard procedure has been confirmed by different methods. Polyacrylamide (10%) gel electrophoresis at pH 8.1 of intact or "spontaneously"degraded neutral salt soluble collagen results in the separation of two components: the upper one says at the origin and represents collagen or collagen ragments, whereas the lower protein component contains no collagen, often preserves specific collagenolytic activity, and migrates as a single band in SDS/polyacrylamide electrophoresis. With lower polyacrylamide gel concentration the electrophoretic separation of the two components is less clear. Removal of the lower protein component from collagen solutions by two different methods (TCA-ethanol purification cycles and pepsin digestion) results in concomitant loss of their "spontaneous" instability. Eluates of the lower protein component stimulate the heterologous production of a monospecific antibody capable of inhibiting the collagenolytic activity of homologous crude collagenase preparations. It is suggested that collagen-bound collagenase is not an artifact of the extraction procedure but rather a physiological reality, probably corresponding in the living animal to the enzyme closely associated with extracellular collagen fibers, revealed by immunohistochemical methods. PMID- 6256124 TI - The chemistry and biology of cholera toxin. PMID- 6256125 TI - Structural analysis of electrical properties of cells and tissues. AB - Most cells and tissues have electrical properties relevant to their natural function. Most cells and tissues have rather complex structure, consisting of folding and invaginating membranes and specialized connections and organelles. The localization of electrical properties is particularly important, since each of the complex structures must be expected to have a specific role in the electrical function of the tissue. The structural analysis of electrical properties consists then in the measurements of the electrical properties of the individual components of the tissue or cell. The structural analysis proceeds by a qualitative analysis of the topology of the preparation, followed by quantitative measurements of the morphometric parameters, the surface, and volume of the relevant structures. A theoretical analysis is performed to determine the electrical properties expected from such a structure. Measurements of natural and induced electrical properties are then made. Comparison of the observed electrical properties with those predicted allows determination of the properties of individual components of the tissue. In this manner the role of individual membrane systems in the function of both skeletal muscle and the lens of the eye has been determined. PMID- 6256126 TI - Vitamin D and the regulation of calcium absorption in the small intestine. PMID- 6256127 TI - [Effect of the work environment on acid phosphatase and lysozyme activity in the saliva of workers in phosphate fertilizer plants]. PMID- 6256128 TI - Angiotensin-converting enzyme in farmer's lung. AB - Serum levels of angiotensin-converting enzyme were measured in a group of patients with farmer's lung and a group of precipitin-positive subjects with no history of farmer's lung. The levels did not differ significantly from control subjects matched for age and smoking history. The mean serum level of angiotensin converting enzyme in a group of acutely ill patients with farmer's lung was significantly reduced. An acute challenge of three patients with Micropolyspora faeni did not produce an increase in serum levels of angiotensin-converting enzyme. These studies suggest that an increased serum level of angiotensin converting enzyme can be a diagnostic aid in making a differential diagnosis between sarcoidosis and farmer's lung. PMID- 6256129 TI - Small cell carcinoma of the lung. Is histologic subtyping important? PMID- 6256130 TI - Endorphins and acupuncture analgesia. PMID- 6256132 TI - Subnormal inhibition of active E rosette formation by isoproterenol in bronchial asthma. AB - Three different groups of patients were studied: group A was on active attacks of asthma with bronchodilator therapy; group B was also on active attacks of asthma but free of any treatment; and group C was of remissive asthma due to hyposensitization, and free of any other treatment. Active E rosette forming populations of all the three groups showed much less reduction by beta-adrenergic agonist isoproterenol as comparing to normal controls, but had equal degrees of inhibition by cAMP and theophilline to normal subjects. Dysfunction of beta adrenergic receptors in bronchial asthma, as presented in this study, was in accordance with Szentivanyi's theory of beta-adrenergic blockage. Therapy with sympathomimetic bronchodilators might have desensitizing effect on beta adrenergic receptors. Symptom-relieving hyposensitization could'nt restore the beta-receptor functions in asthmatic patients. The significance of beta-receptor dysfunction in bronchial asthma was discussed. PMID- 6256133 TI - [Prevalence of hepatitis virus infections in restaurant workers in Taipei (author's transl)]. AB - Hepatitis B surface antigen (HBsAg) and anti-hepatitis A virus antibody (antiHAV) in sera or saliva of restaurant workers in Chung Shan District, Taipei, were tested by radioimmunoassay from October 1978 to March 1979. Among the 2006 serum samples 387 (19.3%) were HBsAg positive. While significant difference between male and female restaurant workers was observed, no age difference was noted. The workers originated from Taiwan demonstrated the highest frequency of hepatitis B antigenemia (20.9%). The next high group was the workers originated from southern mainland (16.5%). The lowest frequency was observed in those from northern mainland (9.4%). HBsAg was found in saliva of 40 out of 82 serum carriers (48.8%) Of the 946 workers 896 (94.7%) carried the anti-HAV antibody. There was no sex difference and the positive rates were 91.2%, 92.6%, 96.1%, 98.4% in 14--19, 20- 24, 25--29 and > 30 years old population, respectively, i.e. a trend of increase in the rates with age was observed. PMID- 6256131 TI - Hot lymphocyte E rosette formation and its effect on changes in endogenous lymphocyte cAMP levels. PMID- 6256134 TI - [Incidence of gangrene of the external genital organs in Abidjan during a 10-year period: report on 90 cases and review of the literature (author's transl)]. PMID- 6256135 TI - [A case of glucagonoma in a 72-year-old woman. Cephalic duodenopancreatectomy. Result after 1 year and a half (author's transl)]. PMID- 6256136 TI - [A rare pancreatic tumour: the glucagonoma (author's transl)]. PMID- 6256137 TI - Absence of short-period repetitive-sequence interspersion in the basidiomycete Schizophyllum commune. AB - Reassociation kinetics and electron microscopy were used to examine the organization of DNA sequences in the Basidiomycete Schizophyllum commune. Short period interspersion of repetitive and unique sequences is absent from the DNA of this wood-rotting fungus. Instead, repetitive sequences are found predominantly in several, perhaps 16, clusters averaging 225 kilobases in length. The results of this study, the first concerning a fungus in the important fungal Class Basidiomycetidae, are discussed in relation to: sequence organization in three other species of true fungi, fungal evolution and the regulation of gene expression. PMID- 6256138 TI - Clinical chronopharmacology of ACTH 1-17. I. Effects on plasma cortisol and urinary 17-hydroxycorticosteroids. AB - The aim of the investigation was to study the effects of ACTH 1-17 on both plasma cortisol and urinary 17-OHCS in health adult young males with regard to the time (clock hours) at which this polypeptide was injected. Eight healthy adults (males from 18-30 years) volunteered for the study. They were synchronized with a diurnal activity from 0700 to 0000 and a nocturnal rest. Each week, during 6 consecutive weeks (January 19 to February 25, 1980), a 3-day test was performed on Saturday, Sunday and Monday. On Sundays 3 control-tests and 3 ACTH-tests were programmed during which either saline or 100 micrograms ACTH 1-17 were injected i.m. at respectively 0700, 1400 and 2100. During each 3 day-test (72 h) the urinary excretion of 17-OHCS was determined every 4 h at fixed clock hours. In addition, on Sundays, venous blood was sampled prior to control or ACTH injections at respectively 0700, 1400, and 2100 and 20, 40, 60, 90, 120, 150 and 180 min thereafter. Plasma cortisol (radioimmunoassay) was determined in samples thus collected. Both conventional and cosinor methods were used for statistical analyses. A strong and statistically significant rise of plasma cortisol was observed after all of the ACTH 1-17 injections. The obtained mean response curves were observed after all of the ACTH 1-17 injections. The obtained mean response curves were similar in form and parallel. The highest plasma cortisol curve corresponded to ACTH injected at 0700, the lowest to ACTH injected at 2100. The curve corresponding to ACTH injected at 1400 went in-between. The 24-h urinary excretion of 17-OHCS after ACTH 1-17 was approximately 4 times greater than the control value when injected at 0700, approximately 3 times greater than control when injected at 1400 and only twice greater than control when injected at 2100. In terms of changes in plasma cortisol and 17-OHCS the greatest best benefit of ACTH 1-17 is achieved when this polypeptide is injected at 0700, rather than at 1400 or 2100 in diurnally active subjects. PMID- 6256139 TI - Abnormal membrane characteristics of erythrocytes in rat models and men with predisposition to stroke. AB - Erythrocyte membrane characteristics were examined in normotensive Wistar-Kyoto rats (WK), stroke-resistant spontaneously hypertensive rats (SHRSR) and stroke prone SHR (SHRSP). The membrane of SHRSP was more labile against osmotic shock than that of SHRSR or WK at the age of 2 months. This membrane fragility was not dependent on their blood pressure. The membrane permeability of lipophilic ion, tetraphenylphosphonium, was increased in 1-month old SHRSP. These membrane characteristics in SHRSP were partially dependent on cholesterol amount which was significantly decreased in SHRSP. The method determining the membrane fragility was applied to human erythrocytes. Two groups of people were selected from about 2,000 inhabitants under our community health control program. The erythrocytes from the group with stroke in their family history were more labile than erythrocytes from the corresponding group without stroke in their family history. This result suggests that the examination of these membrane characteristics may give us a new method to detect a genetic risk to hypertension or stroke-proneness also in human. PMID- 6256140 TI - The role of alpha receptors in the facilitation of the chemoreflex and inhibition of the carotid occlusion reflex by clonidine. AB - The influence of alpha receptor blockers on the facilitation of the chemoreflex by clonidine was examined in anesthetized dogs. Intravertebral arterial administration of clonidine reduced blood pressure, facilitated chemoreflex induced vasoconstriction and inhibited carotid occlusion-induced vasoconstriction. Intravertebral arterial administration of phentolamine (0.01 0.03 mg/kg), yohimbine (0.01-0.02 mg/kg), or piperoxan (0.05 mg/kg) prevented the inhibition of carotid occlusion-induced responses by clonidine, and the latter two alpha blockers reduced the hypotensive effect. Facilitation of the chemoreflex by clonidine was decreased by yohimbine and piperoxan, but not affected by phentolamine. Intravertebral infusion of propranolol (0.1 mg/kg) had no influence on clonidine's effect on reflex responses, but appeared to accentuate its hypotensive effect. The results support a role for alpha receptor stimulation in clonidine-induced hypotension and inhibition of the carotid occlusion reflex and suggest participation of alpha receptors in the potentiation by clonidine of chemoreflex-induced vasoconstriction. PMID- 6256141 TI - Separation of angiotensin receptor from cell membrane angiotensinase in rabbit aorta. AB - Deoxycholic acid (0.01%) diminished the tissue response to angiotensin in rabbit aortic strips. A lower maximal response was obtained, but the affinity of angiotensin receptors did not change. Specific angiotensin receptor binding was measured in cell membrane fraction, solubilised fraction and pellet fraction after solubilization. The solubilised fraction showed threefold increase in receptor binding and was devoid of angiotensinase activity. The binding to pellet fraction after solubilization was increased or unchanged and contained the same angiotensinase activity as before solubilization. We conclude that it is possible to separate angiotensin receptor from cell membrane angiotensinase. PMID- 6256143 TI - [Spectral studies of photochemical reactions in blood]. PMID- 6256142 TI - Effect of prostaglandin on ion transport across isolated colonic mucosa. AB - The effect of prostaglandins (PG) on colonic ion transport was investigated in in vitro experiments in the rat. Both PGE1 and PGA1 increased short-circuit current (Isc), potential difference, and mucosal cyclic AMP levels, but PGE1 was more potent than PGA1. 10(-4) M PGE1 inhibited active sodium transport across short circuited colonic mucosa (6.1-1.3 microEq/hr/cm2). This effect, coupled with an increase in Isc, is consistent with prostaglandin stimulation of active anion secretion and with the recent suggestions that prostaglandins may be important intermediaries in the process by which several laxatives alter large-intestinal fluid and electrolyte movement. PMID- 6256144 TI - [Thyroxine binding by nuclear structures of rat myocardium]. PMID- 6256146 TI - [Skull surgery in the Kisii (Gusii) in the highlands of Western Kenya]. PMID- 6256145 TI - [Identification of carriers of chronic granulomatous disease (author's transl)]. AB - Chronic granulomatous disease is caused by an X chromosome-linked granulocyte function defect whereby the superoxide radical (O2-) and hydrogen peroxide are not formed during phagocytosis. In the course of the investigation of the family of a boy with chronic granulomatosis disease carriers could not be established using the NBT test. Only determination of O2- formation by granulocytes during phagocytosis led to identification of disease carriers. This may possibly represent a means for prenatal diagnosis. PMID- 6256147 TI - Aqueous humour pralidoxime mesylate (P2S) concentrations and intraocular tension following intramuscular P2S. AB - Small transient increases in rabbit intraocular tension were measured following intramuscular pralidoxime mesylate (P2S) at doses of 10, 40 or 100 mg/kg. Peak increases in tension showed some dose dependency, and although not statistically correlated with plasma or aqueous humour P2S concentrations the changes in tension followed the general time-concentration profile for P2S in these fluids. P2S was not detected in aqueous humour following 10 mg/kg, but at 40 and 100 mg/kg dose dependent concentrations were detected in aqueous humour. From experiments involving multiple injections of P2S there was no evidence for a cumulative effect of P2S on the eye. The results indicate that P2S can enter aqueous humour following its parenteral administration and is associated with changes in intraocular fluid dynamics. Whilst they also suggest that some ophthalmic side-effects of oxime therapy may be a consequence of a direct action of the oxime on the eye, they do not exclude contributions from actions at other sites. PMID- 6256148 TI - Studies on the use of activated charcoal and cholestyramine for reducing the body burden of polybrominated biphenyls. AB - Weanling male rats were exposed to a polybrominated biphenyl (PBB) mixture (Firemaster FF-1) in their diet so that they received 1 mg/kg/day for 6 months. They were then fed a normal diet for 4 months. Following this they were placed on diets containing either activated charcoal (AC) or cholestyramine (CSA) for 6 months to evaluate the usefulness of these compounds in reducing the body burdens of the retained PBBs. Periods of restricted caloric intake were also used in an effort to mobilize PBBs stored in fat. Neither compound nor restricted caloric intake was found to be effective in reducing tissue bromine levels but CSA proved useful in preventing the progression of chronic progressive nephropathy, a spontaneous lesion of aging rats. PMID- 6256149 TI - [New drugs against herpesviruses]. PMID- 6256151 TI - Stimulation of a D-2 dopamine receptor in the intermediate lobe of the rat pituitary gland decreases the responsiveness of the beta-adrenoceptor: biochemical mechanism. AB - In experiments using a cell-free homogenate of the intermediate lobe of the hypophysis of the rat, apomorphine, a dopaminergic agonist, diminished both basal and L-isoproterenol-stimulated adenylate cyclase activity; dopaminergic antagonists from several chemical families reversed these inhibitory effects of apomorphine. Apomorphine diminished the ability of GTP to enhance both basal and L-isoproterenol-stimulated adenylate cyclase activity but did not directly interfere with the interaction between the beta-adrenoceptor and L-isoproterenol. The affinity of the D-2 dopamine receptor in the intermediate lobe for each dopaminergic antagonist used in this study was estimated from a mathematical analysis of the data. (Endocrinology 108: 420, 1981) PMID- 6256150 TI - des-Asp-angiotensin I: its identification in rat blood and confirmation as a substrate for converting enzyme. AB - The observation that angiotensin III is present in the circulation of the rat in amounts similar to those of angiotensin II has led to the notion that it may, in part, be formed by the action of converting enzyme on des-Asp-angiotensin I without the prior formation of angiotensin II. This possibility was studied in conscious rats using a combination of RIA and chromatographic techniques which allowed the separate measurement of angiotensin I, des-Asp-angiotensin I, angiotensin II, and angiotensin III in rat blood. Infusion of des-Asp1 [Ile5]angiotensin I at 50, 150, and 450 ng/kg . min resulted in a progressive increase in the plasma concentration of angiotensin III up to 279 +/- 50 (SD) pg/ml compared to 9 +/- 9 (SD) pg/ml after dextrose infusion. Regardless of the infusion of des Asp-[Ile5]angiotensin I, plasma angiotensin III made up a constant 46 +/- 8% (+/- SD) of the total immunoactive material, the remainder being composed of smaller metabolic fragments, indicating a rapid rate of clearance of angiotensin III. Captopril completely inhibited the rise in angiotensin III after des-Asp1-[Ile5]angiotensin I infusion. A substance which chromatographed as des-Asp-[Ile5]angiotensin I was detected in rat blood and made up 19% of the angiotensin I immunoactive material, while angiotensin III made up 44% of the angiotensin II immunoactive material. These results confirm that des Asp1-[Ile5]angiotensin I is a substrate for converting enzyme in the rat, and the presence of a chromatographically similar substance in the circulation suggests that at least part of the angiotensin III in rat blood may be formed by the action of converting enzyme on endogenous des-Asp-angiotensin I. (Endocrinology 108: 406, 1981) PMID- 6256152 TI - Regulation of protein kinase inhibitor by follicle-stimulating hormone in Sertoli cells in vitro. AB - The heat-stable protein inhibitor of cAMP-dependent protein kinase is specifically regulated by hormones in cultures of rat Sertoli cells maintained under completely defined conditions. Hormones that are known to elevate Sertoli cell cAMP concentrations, namely FSH and isoproterenol, produce a 4- to 5-fold increase in the specific activity of protein kinase inhibitor, whereas testosterone and LH have no effect. The stimulatory effects of FSH or isoproterenol on protein kinase inhibitor are completely mimicked by dibutyryl cAMP. The ability of FSH to stimulate protein kinase inhibitor is dependent upon the age of the animals used as a source for the Sertoli cells. FSH stimulates protein kinase inhibitor activity in cells from 9- and 16-day-old animals, but not in cells from 32-day-old animals. On the other hand, isoproterenol or dibutyryl cAMP will stimulate protein kinase inhibitor in cells from both young and old animals. FSH can stimulate protein kinase inhibitor activity in older cells only in the added presence of the phosphodiesterase inhibitor, 1-methyl-3 isobutyl xanthine. Using specific antibodies to protein kinase inhibitor, we have shown that this protein is regulated by hormones via preferential stimulation of de novo synthesis of the inhibitor. (Endocrinology 108: 427, 1981) PMID- 6256153 TI - Orally active mineralocorticoid agonists and antagonists: delta 1-derivatives of aldosterone and 18-deoxyaldosterone. AB - The effect of delta 1 unsaturation on the oral effectiveness of a representative mineralocorticoid agonist and antagonist was investigated in an adrenalectomized rat bioassay. Dehydrogenation at the 1.2 position did not alter the qualitative nature of the mineralocorticoid activity of the parent compound. Thus delta 1 aldosterone (21,18-dihydroxy-11 beta, 18-oxido-1,4-pregnadiene-3,20-dione) retained pure mineralocorticoid agonism, and delta 1-18-deoxyaldosterone (21 hydroxy-11 beta, 18-oxido-1,4-pregnadiene-3,20-dione)demonstrated the same relative degree of predominant antagonism as 18-deoxyaldosterone (21-hydroxy-11 beta, 18-oxido-4-=pregnene-3,20-dione) itself. In each instance, receptor affinity was diminished by 1,2 unsaturation, but this effect was offset by the greater bioavailability of the delta 1 derivatives on oral administration. (Endocrinology 108: 517, 1981) PMID- 6256154 TI - Mechanisms of inhibition of aldosterone secretion by adrenocorticotropin. AB - The mechanisms by which prolonged administration of ACTH causes a decrease in aldosterone secretion were studied in the rat. After 6 days of treatment with ACTH (2 U/day), blood corticosterone was elevated and plasma aldosterone was decreased in rats maintained on either a normal or low sodium diet. PRA was also decreased, probably secondary to increased sodium and/or fluid retention. In collagenase-dispersed glomerulosa cells from adrenals of ACTH-treated rats, angiotensin II receptors were markedly decreased, as were the in vitro aldosterone responses to angiotensin II, ACTH, 8-bromo-cAMP, and potassium. However, the production of deoxycorticosterone and precursor steroids was increased, indicating the presence of a block in the late aldosterone biosynthetic pathway. Measurement of the activity of biosynthetic enzymes of the steroidogenic pathway in isolated mitochondria revealed an 80% increase in side chain cleavage enzyme in both glomerulosa and fasciculata mitochondria from ACTH treated rats. Although ACTH injection also increased 11-hydroxylase activity in the fasciculata zone, this enzyme was reduced by 50% in capsular mitochondria. The 18-hydroxylase activity in adrenal capsular mitochondria was markedly decreased by ACTH treatment in both normal and sodium-restricted animals. The importance of ACTH-induced steroidogenesis in the development of altered glomerulosa cell function was indicated by the ability of aminoglutethimide to prevent the inhibitory effects of ACTH on angiotensin II receptors and PRA. It is likely that the observed inhibition of the renin-angiotensin system is responsible for the decrease in angiotensin II receptors and 18-hydroxylase, since both are highly dependent on the trophic effect of angiotensin II. The specific lesions produced in adrenal glomerulosa cells by long term ACTH treatment include decreased levels of angiotensin II receptors, 11-hydroxylase, and 18-hydroxylase. These changes are secondary to the suppression of renin angiotensin activity and are responsible for the impaired aldosterone secretion that results from prolonged treatment with ACTH. (Endocrinology 108: 522, 1981) PMID- 6256155 TI - Responses of blood pressure and angiotensin-converting enzyme activity to acute captopril administration in normotensive and hypertensive rats. AB - The purpose of these experiments ws to determine the dose of captopril which resulted in essentially complete blockade of tissue and plasma converting enzyme activity (CEA) and to correlate the effect of this dose of inhibitor on blood pressure and CEA in a number of normotensive and hypertensive rat models. Oral administration of captopril (0.3-10 mg/kg) induced a dose-related attenuation of CEA in plasma freshly drawn from normotensive conscious rats. After storage at 20 or 4 C before assay, both captopril-treated and untreated plasmas displayed markedly greater CEA. The converting enzyme inhibitor induced a parallel shift to the right of angiotensin I-induced blood pressure responses, reaching a 100-fold displacement of dose-dependent responses in the presence of 10 mg/kg captopril. Sixty minutes after oral administration of 10 mg/kg captopril, plasma CEA was blocked completely in all normo- and hypertensive models studied. This dose of the inhibitor reduced blood pressure in the sodium-deplete normotensive rat, the spontaneously hypertensive rat, and the initial phase two-kidney, one-clip Goldblatt rat but not in the sodium-replete normotensive rat, the spontaneously hypertensive rat, the mineralocorticoid hypertensive rat, or the chronic phase of two-kidney, one-clip Goldblatt rat. It is concluded that acute administration of captopril at a dose which results in complete blockade of plasma converting enzyme and severe attenuation of tissue converting enzyme reduces blood pressure in animals with high PRA but not in animals in which the PRA is low. (Endocrinology 108: 536, 1981) PMID- 6256157 TI - Ontogenesis of glucocorticoid receptors in anterior pituitary gland: transient dissociation among cytroplasmic receptor density, nuclear uptake, and regulation of corticotropic activity. AB - The present investigation was undertaken to define the developmental pattern of glucocorticoid binding to the anterior pituitary gland and ascertain whether that binding correlated to modulation of corticotropin-releasing factor-induced release of ACTH. Scatchard analysis of data revealed the presence in cytosol (besides classical receptor sites interacting with both [3H]dexamethasone and [3H]corticosterone) of a transcortin-like component binding only the natural steroid. Whereas the number of sites of the former binder was not significantly altered during maturation and remained close to the adult value (276 +/- 12 fmol/mg protein), that of the latter declined dramatically after birth and rose again after postnatal day 10. The apparent Kd, however, remained unchanged. Transfer of te [3H]dexamethasone-receptor complex to nuclei of pituitary cells from neonates 2-6 days of age was found to be 20% that of adults despite the presence of comparable concentrations of receptor sites. Mixing experiments carried out with cytosol and nuclear fractions from different origins pointed to the cytoplasmic compartment as being implicated in this discrepancy. It was not until after postnatal day 10 that nuclear transfer reached mature levels. Although the extent of nuclear uptake and the magnitude of inhibition of ACTH secretion, as judged by means of a perifusion system, correlated well in hypophyses from 10- to 30-day-old neonates and adults, steroid binding and induction of biological response at earlier time points were less closely related. The results indicate the existence during development of a transient dissociation between cytosol and nuclear binding of corticosteroids by the anterior pituitary as well as between the latter process and blockade of ACTH release. These data are discussed in connection with the postnatal period nonresponse to stress. (Endocrinology 108: 591, 1981) PMID- 6256156 TI - Neonatal rat pinealocytes: typical and atypical characteristics of [125I]iodohydroxybenzylpindolol binding and adenosine 3',5'-monophosphate accumulation. AB - Techniques are described which make it possible to study beta-adrenergic receptors on intact neuroendocrine cells. Receptors were characterized on neonatal pinealocytes using the radioligand [125I]iodohydroxybenzylpindolol ([125I]IHYP). Specific binding of [125I]IHYP, which is 4-fold greater than nonspecific binding, is concentration and temperature dependent, reversible, and saturable. [125I]IHYP binds noncooperatively (Kd = 35 pM), and Scatchard analysis indicates that only a single class of receptor sites for [125I]IHYP is present. Under the conditions used, it appears that there are about 12,000 +/- 1,100 sites/cell. Inhibition of specific [125I]IHYP binding by beta-adrenergic agonists and antagonists is stereospecific, and the relative potency of agonists is characteristic of binding to beta-adrenergic receptors. Analysis of adrenergic stimulation of intracellular cAMP accumulation indicates that similar half maximal concentrations of antagonists inhibit [125I]IHYP binding and adrenergically stimulated cAMP accumulation. In contrast, beta-adrenergic agonists are considerably more potent in stimulating cAMP than in inhibiting [125I]IHYP binding. Unexpected differences, not previously reportd, were found in the shapes of the cAMP accumulation dose-response curves of norepinephrine and isoproterenol. The relative potencies of these two agonists appear to be partially concentration dependent. This raises the possibility that there may be distinct differences in the intrinsic effects of these compounds on the regulation of intracellular cAMP accumulation in pinealocytes. (Endocrinology 108: 559, 1981) PMID- 6256158 TI - Insulin release in aging: studies on adenylate cyclase, phosphodiesterase, and protein kinase in isolated islets of Langerhans of the rat. PMID- 6256159 TI - Changes in Leydig cells and luteinizing hormone receptors in porcine testis during postnatal development. AB - LH receptors have been characterized in porcine testis (Sus crofa L.) from birth to 220 days of age and have been related to interstitial tissue development (especially Leydig cells). The mean association constant (Ka) of ovine [3H]LH, was 7 +/- 6 X 10(9) M-1, with no apparent age-dependent variation but with some significant individual variations. The concentration of specific LH receptor sites reached a maximum of 9 X 10(-12) M/g testis between days 20-70, decreased to 3 X 10(-12) M/g testis at the onset of puberty (up to 100 days), and remained stable at the same level in the adult. The total number of sites per testis essentially reflected the growth of the testis. Interstitial tissue occupied up to 80% of the volume of the whole testis during the occupied up to 80% of the volume of the whole testis during the first 30 neonatal days. It decreased to about 25% after 120 days. The Leydig cells in this tissue occupied the same proportion (70% of the volume of the whole testis) regardless of the age of the animals. The mean Leydig cell diameter reached a maximum of 20 micrometer at 30 days of neonatal life, decreased to a minimum of 10 micrometer at 90 days, and then increased to a stable value of 15 micrometer after puberty. The number of Leydig cells per unit volume varied with age, with a maximum of 3 X 10(8) cells/ml testis at 90 days, reaching a constant value of 6 X 10(7) cells/ml testis after puberty. These data suggest that each Leydig cell contains 80,000 specific LH-binding sites/cell 30 days after birth and 35,000 in the adult, with no observed periods without receptor sites. The number of receptors per cell is correlated to cell size rather than stage of sexual maturation. (Endocrinology 108: 625, 1981) PMID- 6256160 TI - The dynamics of the steroidogenic response of perifused Leydig tumor cells to human chorionic gonadotropin, ovine luteinizing hormone, cholera toxin, and adenosine 3',5'-cyclic monophosphate. AB - A perifusion system has been developed in which a dose-dependent response of isolated Leydig tumor cells to steroidogenic stimuli, as assessed by the rates of steroid production, can be measured as a function of time. In response to a continuous perifusion for 340 min with a saturating concentration of hCG, ovine LH (oLH), cholera toxin, or 8-Br-cAMP, there is a rapid increase in the rate of progesterone production, which reaches a maximum about 100 min after the onset of stimulus in the medium and then declines to a rate somewhat higher than basal. Thus cholera toxin and 8-Br-cAMP as well as hCG and oLH are able to desensitize the Leydig tumor cells to further stimulation by the same agent. Although a 10 min pulse of a saturating concentration of hCG yields the same steroidogenic response as that elicited by continuous perifusion with saturating hCG, a pulse of a saturating concentration of oLH yields a steroidogenic response only when oLH is maintained in the perifusate. These data establish a substantial difference in the actions of hCG and oLH. The results could be explained by the higher apparent affinity of hCG for the gonadotropin receptor, such that, upon removal of hormone from the perifusate, oLH would be more readily eluted from the receptor. These findings support the hypothesis that oLH and hCG exert their stimulatory effects only while bound to the cell surface. (Endocrinology 108: 632, 1981) PMID- 6256161 TI - Myocardial beta-adrenergic receptors from adrenalectomized rats: impaired formation of high-affinity agonist-receptor complexes. AB - Adrenal steroid hormones potentiate beta-adrenergic actions on the heart. Accordingly, we investigated the effects of adrenalectomy on agonist and antagonist interactions with myocardial beta-adrenergic receptors and adenylate cyclase. The affinity and number of beta-adrenergic receptor sites, both defined by the antagonist (-) [3H]dihydroalprenolol, did not change after adrenalectomy. Computer modelling of agonist (-)-isoproterenol competition curves indicated the presence of two discrete receptor states with high and low affinities. After adrenalectomy, the agonist curves were shifted to the right, and the dissociation constant of the high-affinity state significantly rose from 12 to 48 nM (p < .001), but the dissociation constant of the low affinity state was unchanged. Although basal, maximal isoproterenol-stimulated and fluoride-stimulated adenylate cyclase activities were unaltered, the EC50 for isoproterenol stimulation was increased significantly from 490 to 1500 nM (p <.018). These results suggest that adrenal steroid hormones may regulate the ability of the beta-adrenergic receptors to form a high-affinity "coupled" state, presumably by modulating the interaction of the receptor with nucleotide regulatory proteins. PMID- 6256163 TI - Levels of glycolytic enzymes in the red blood cells of Australian Aborigines. AB - Blood samples wer collected from three populations of full-blood Aborigines, and twelve different enzymes were assayed in red blood cells. These results were compared with those of Caucasian controls. In the majority of enzymes studied significant differences were observed between the Aboriginal populations and also between individual Aboriginal populations and the Caucasian controls. PMID- 6256162 TI - Insulin permits parathyroid hormone stimulation of 1,25-dihydroxyvitamin D3 production in cultured kidney cells. AB - Primary cultures of chick kidney cells in serum free medium respond to PTH with increased production of 1,25(OH)2D3 only when exposed to insulin. The response of 1,25(OH)2D3 is maximal at 5 ng bPTH (1-34) per ml and decreases at higher hormone concentrations. Increased 1,25(OH)2D3 synthesis is not evident after 30 minutes exposure to bPTH and is maximal at 4-6 hours of treatment. Insulin does not increase the cyclic AMP response to PTH suggesting that whatever permissive role it is playing occurs beyond the generation of cyclic AMP. PMID- 6256164 TI - Purification and characterization of nucleoside diphosphatase from rat-liver microsomes. Evidence for metalloenzyme and glycoprotein. AB - Nucleoside diphosphatase was purified from rat liver microsomes more than 3000 fold with a 16% yield using a procedure including concanavalin-A--Sepharose and phenyl-Sepharose column chromatography. The purified enzyme had a specific activity of 2500 units/mg protein and appeared homogeneous by gel electrophoresis. The enzyme had a sedimentation coefficient of 6.5 S by sucrose density gradient centrifugation. The enzyme had a sedimentation coefficient of 6.5 S by sucrose-density gradient centrifugation, and a Stokes' radius of 4.8 nm was estimated by the gel filtration technique. Its molecular weight is 130,000, but only one single band of Mr 65,000 was detected after sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The native enzyme seems thus to be composed of two identical subunits. The purified enzyme was confirmed to be a glycoprotein containing approximately 9% carbohydrates. The enzyme had a pH optimum of 7.5, an isoelectric point of 4.85 and a Km of 2.5 mM for UDP. On the basis of direct measurement of metal content in the native enzyme, the rat liver nucleoside diphosphatase was found to be a metalloenzyme containing 0.9 mol zinc and 0.1 mol manganese/mol 65,000-Mr subunit. Metal-free nucleoside diphosphatase has been prepared. The activity of the metal-free enzyme was restored by the addition of several divalent cations, zinc being the most effective. PMID- 6256165 TI - DNA polymerase I and recBC enzyme support the covalent closing of hydrogen-bonded lambda DNA circles in extracts of Escherichia coli cells. AB - The covalent closing of hydrogen-bonded lambda DNA circles in Escherichia coli extract was observed to require DNA polymerase I, recBC enzyme and ATP. This covalent closing activity was lost in strains harbouring a mutation in one of the genes responsible for production of the enzymes mentioned above, and was recovered by combining these mutant extracts. ATP could be replaced with dATP, but not appreciably with any of the other nucleoside triphosphates. High concentrations of ATP inhibited the closure. K+ or NH4+ (0.2M) was required for optimal activity and NMN was a strong inhibitor. PMID- 6256166 TI - Purification and properties of a mouse-cell DNA-repair endonuclease, which recognizes lesions in DNA induced by ultraviolet light, depurination, gamma-rays, and OsO4 treatment. AB - A DNA-repair endonuclease has been purified 117-fold from mouse plasmacytoma cells (line MPC-11) by gel filtration, followed by ion-exchange and affinity chromatography. Its molecular weight was determined by gel filtration to be 28,000 +/- 2000. The enzyme recognizes apurinic and apyrimidinic sites induced by acid and gamma-rays in DNA, as well as another type of lesion(s) which is introduced into DNA by both ultraviolet irradiation and OsO4. Quantitative measurements of the number of nicks the purified DNA-repair endonuclease makes in DNA treated with various amounts of OsO4 and ultraviolet light suggests that the endonuclease may act on 5,6-dihydroxydihydrothymine lesions. The endonuclease activity was sensitive to the ionic strength and was most active in the presence of 100 mM KCl, whereas the presence of divalent cations did not stimulate the activity. PMID- 6256167 TI - Identification of amino-acid substitutions in the proteolipid subunit of the ATP synthase from dicyclohexylcarbodiimide-resistant mutants of Escherichia coli. AB - The amino acid sequence of the proteolipid subunit of the ATP synthase was analyzed in six mutant strains from Escherichia coli K12, selected for their increased resistance towards the inhibitor N,N'-dicyclohexylcarbodiimide. All six inhibitor-resistant mutants were found to be altered at the same position of the proteolipid, namely at the isoleucine at residue 28. Two substitutions could be identified. In type I this residue was substituted by a valine resulting in a moderate decrease in sensitivity to dicyclohexylcarbodiimide. Type II contained a threonine residue at this position. Here a strong resistance was observed. These two amino acid substitutions did not influence functional properties of the ATPase complex. ATPase as well as ATP-dependent proton-translocating activities of mutant membranes were indistinguishable from the wild type. At elevated concentrations, dicyclohexylcarbodiimide still bound specifically to the aspartic acid at residue 61 of the mutant proteolipid as in the wild type, and thereby inhibited the activity of the ATPase complex. It is suggested that the residue 28 substituted in the resistant mutants interacts with dicyclohexylcarbodiimide during the reactions leading to the covalent attachment of the inhibitor to the aspartic acid at residue 61. This could indicate that these two residues are in close vicinity and would thus provide a first hint on the functional conformation of the proteolipid. Its polypeptide chain would have to fold back to bring together these two residues separated by a segment of 32 residues. PMID- 6256168 TI - The inhibition and activation of Ca2+-dependent phosphatidylinositol phosphodiesterase by phospholipids and blood plasma. AB - 1. Phosphatidylinositol-phosphodiesterase (EC 3.1.4.10) was strongly inhibited when ovophosphatidylcholine and saturated phosphatidylcholines with acyl chain lengths of more than eight carbon atoms were mixed with its substrate. In contrast, dihexanoylglycerophosphocholine produces a marked activation attended by a breakdown of the bilayer structure of the substrate. 2. C12, C14, and C16 lysophosphatidylcholines gave a progressive inhibition of the enzyme with increasing chain length; C10 lysophosphatidylcholine activated the reaction. 3. The enzyme was strongly inhibited by blood plasma and serum and by blood lipoproteins. 4. Phosphatidic acid, and certain lysophosphatidic acids (oleoyl and palmitoylglycerophosphates) activated the hydrolysis at a physiological pH, whereas decanoylglycerophosphate had little effect. 5. Phosphatidic acid at a concentration of 1% molar total lipid P produced an enhancement of the hydrolysis of the phosphatidylinositol substrate contained in a lipid environment which approximated to the inner (cytoplasmic) lamella of the plasma membrane bilayer of the liver sinusoidal cell surface. 6. The possible role of phospholipid molecules adjacent to phosphatidylinositol in controlling the hydrolysis of the latter in the proximity of a cell surface receptor is discussed. It is suggested that phosphatidic acid formed by the action of diacylglycerol kinase could amplify any increased hydrolysis of phosphatidylinositol which results from stimulation of the cell by an agonist. PMID- 6256169 TI - Lack of ornithine decarboxylase activity in isolated rat liver parenchymal cells. AB - Polyamines are associated with fundamental metabolic and functional steps in cell metabolism. The activity of ornithine decarboxylase, the key enzyme in polyamine metabolism, was followed during the preparation of rat liver parenchymal cells and in the isolated cells during incubation. In experiments in which ornithine decarboxylase was not induced in vivo, enzyme activity dropped to barely measurable values during the preparation. An even more drastic loss of enzyme activity was noted in livers in which ornithine decarboxylase activity was stimulated in vivo 20-40fold by previous injection of bovine growth hormone, or thioacetamide or elevated because of circadian rhythmical changes of the enzyme activity. Within the first 20 min of liver perfusion to disintegrate the tissue, ornithine decarboxylase activity decreased by up to 80%. The presence of bovine growth hormone during cell preparation cannot prevent the loss of enzyme activity. Incubation of the isolated cells for periods of up to 240 min did not restore the enzyme activity. Furthermore, incubation of the cells with bovine growth hormone did not induce ornithine decarboxylase, even though the medium was supplemented with amino acids in physiological concentrations. During normal liver perfusion and in contrast to the situation with isolated cells, there is no loss of enzyme activity but a small rise. Following pretreatment of the animals with bovine growth hormone or thioacetamide the highly stimulated activity of ornithine decarboxylase declined slowly during liver perfusion, but never dropped to values lower than normal for perfusion periods of up to 240 min. Moreover, in the intact perfused organ ornithine decarboxylase remains responsive to bovine growth hormone. The experiments demonstrate that enzymatic tissue dispersion by collagenase in particular or the preparation of isolated cells in general drastically alters the metabolic and functional state of rat liver parenchymal cells. PMID- 6256170 TI - Effects of cytochalasin B and enucleation on EGF receptor down regulation. AB - The loss of epidermal growth factor (EGF) binding activity on cultured murine 3T3 cells exposed to EGF (EGF receptor down regulation) was determined in colchicine treated cells, cytochalasin B treated cells, and untreated cells. Neither colchicine nor cytochalasin B altered the affinity of the receptor for EGF, but colchicine decreased maximal EGF binding activity by 20%. The maximal extent of EGF receptor down regulation was similar in colchicine treated cells and cytochalasin B treated cells, but the rate of receptor down regulation was higher in cytochalasin B treated cells. Cytoplasts produced by subjecting cytochalasin B treated cells adhering to the substratum to centrifugal force responded to EGF with nearly normal down regulation kinetics. The results suggest that the cytoskeleton is not obligatorily involved in EGF-induced EGF receptor down regulation. PMID- 6256171 TI - The biochemical basis of immunodeficiency disease. PMID- 6256172 TI - Binding of 3H-beta-endorphin to rat brain membranes: characterization of opiate properties and interaction with ACTH. AB - The binding of tritiated beta-endorphin (3H-beta-EP) to brain homogenates is described. This has been difficult to achieve due to the lack of availability of 3H-beta-EP and to technical difficulties associated with high non-specific binding of beta-EP. We now report that 3H-beta-EP binding is saturable, stereospecific, has high affinity and is inhibited by sodium. Its dissociation rate is ten-fold longer than that of naloxone. Its regional distribution exhibits interesting differences from naloxone and enkephalin binding. ACTH1-24 appears to displace it more effectively than it displaces 3H-naloxone. The results are discussed in terms of multiple transmitter systems and the multiple opiate receptor hypothesis. PMID- 6256174 TI - Effects of hexose infusion with insulin and of additional epinephrtine injection on the levels of serum potassium and blood glucose in dogs. AB - The hypokalemic response was roughly proportional to the dose of insulin. The hypokalemia due to adding insulin to galactose or fructose loading was slightly greater than that with insulin and glucose or mannose loading, suggesting a hexose stereospecificity of the response. When epinephrine (13.6 nmol/kg, i.v.) was given after one of the hexoses plus insulin, the hyperkalemia with glucose and galactose was 2.5-3 mEq/l, about twice that due to fructose or mannose. The hyperglycemia was about 2 mmol/l for glucose, 1 mmol/l for galactose, mannose, fructose, and ouabain with glucose, and 0.25 mmol/l for phloridzin with glucose. Addition of epinephrine, isoproterenol, and cAMP caused a significant depression of Na+,K+-ATPase activity in rat liver (P < 0.01) but the addition of insulin did not. These results show that there was a relation between the levels of blood glucose and serum potassium after an insulin-containing hexose infusion and that membrane permeability was stereospecific. PMID- 6256175 TI - Activation of guinea pig pulmonary adenylate cyclase by prostacyclin. AB - Prostacyclin activates adenylate cyclase of guinea pig lung homogenates. The concentration for half-maximum activation was 20 nM. Kinetic analysis of the increase in enzyme activity suggested a non-cooperative, bimolecular interaction between prostacyclin and a single receptor population. Comparison of the activity of prostacyclin with that of other prostaglandins revealed a rank order of potency: prostacyclin > prostaglandin E1 > prostaglandin E2 > prostaglandin F1 alpha. 6-Oxo-prostaglandin F1 alpha, the stable hydrolysis product of prostacyclin, produced no increase in adenylate cyclase activity. Lungs were dissected before homogenisation, and prostacyclin-sensitive adenylate cyclase was identified at high concentrations in peripheral lung tissue containing small airways, blood vessels and parenchyma. The precise cellular location of these receptors remains obscure, but the probability that they are in the pulmonary vascular bed rather than airway smooth muscle is discussed. PMID- 6256173 TI - Differential effects of amrinone on contractility and taurine influx in rat and guinea pig hearts. AB - Amrinone (5-amino-3,4'-bipyridin-6(IH)-one) is a non-glycoside, non catecholamine, positive inotropic agent with an unknown mechanism of action. In the Langendorff-perfused isolated guinea pig heart, we found that amrinone produced a maximum increase in contractile force of 33% at a concentration of 10 micrograms/ml (10.7 x 10(-5) M), without change in heart rate. Maximum response occurred within 2 min of initiating perfusion, and increased contractility persisted for several minutes of drug-free washout. Amrinone neither alleviated nor aggravated spontaneous arrhythmias. At the time of maximum inotropic response, amrinone produced no change in cyclic AMP levels. In contrast to the guinea pig, the Langendorff-perfused isolated rat heart responded with a decreased contractility when perfused with amrinone. Furthermore, whereas amrinone stimulated the influx of taurine in guinea pig hearts, taurine influx remained unaltered in rat hearts. This is the first case of stimulated taurine influx not being associated with an increase in cAMP concentrations. In the guinea pig heart, amrinone increased markedly the half life of exchange of intracellular calcium. It has been suggested that amrinone is positively inotropic because of a direct action on the contractile proteins. On the basis of our observations, we think it more likely to be due to the alterations in calcium flux caused by amrinone. PMID- 6256177 TI - Induction of angiotensin I-converting enzyme rat lung with Captopril (SQ 14225). AB - Angiotensin I-converting enzyme (ACE, EC 2.4.15.1.) was measured in serum and in pulmonary plasma membranes of 40 spontaneously hypertensive rats (SHR, Okamoto Aoki strain), divided into 4 groups, and treated with SQ 14225 (Captopril), 0.2 mg . ml-1 in drinking water, for 0-24 weeks. Serum ACE activity increased 2.5-3 fold after 12-24 weeks of SQ 14225 treatment, paralleled by an increase of ACE concentration in purified pulmonary plasma membranes (25-52%), and in ACE concentration upon solubilization with Triton X-100 from such plasma membranes (96-120%). We conclude that the ACE inhibitor, SQ 14225, causes marked induction of pulmonary ACE biosynthesis. High serum ACE activity probably reflects increased total biosynthesis of the enzyme. PMID- 6256176 TI - Effect of indomethacin on cardiac beta-adrenergic receptors. AB - Treatment of rats with indomethacin, 1.5 mg/kg per day, for one week, significantly reduced the number of beta-adrenoceptors in the heart without altering their affinity for the specific beta-adrenergic ligand. In indomethacin treated rats there was a reduction in the cardiac response to epinephrine in vivo as indicated by a shift to the right of the epinephrine dose-heart rate response curve. These results support a possible interference by indomethacin in beta adrenoceptor-mediated effects. PMID- 6256178 TI - Identification of alpha 2-adrenergic receptors in human fat cell membranes by [3H]chlonidine binding. AB - 3H-clonidine bound to membrane sites of human fat cells, which have the characteristics of alpha 2-adrenoceptors. Specific binding was rapid, reversible and saturable. [3H]Clonidine binding was of high affinity with a KD of 3.9 nM and with a maximal occupancy of 348 fmol/mg protein. The correlation between alpha adrenergic agonist or antagonist affinities for the membrane [3H]clonidine binding site with their physiological potencies demonstrates the usefulness of the human fat cell as a model for investigating postsynaptic alpha 2-adrenoceptor properties and regulation. PMID- 6256179 TI - Effect of guanethidine on alpha-adrenoceptor blocking potency of phentolamine in vitro. AB - The effect of guanethidine on the alpha-adrenoceptor blocking potency of phentolamine was studied using the rabbit aortic strip and rat vas deferens. The agonists used were noradrenaline (in presence of DOCA and cocaine which block uptake mechanisms) and xylometazoline (which is not taken up by uptake mechanisms). Guanethidine augmented the responses to noradrenaline and xylometazoline and increased the pA2 value of phentolamine against both agonists. Increased affinity of alpha-receptors may be partly responsible for the guanethidine-induced supersensitivity to alpha-adrenoceptor agonists. PMID- 6256181 TI - Supersensitivity of the spinal cord cyclic AMP system following 6 hydroxydopamine. PMID- 6256180 TI - alpha 2-Adrenergic receptors are associated with renal proximal tubules. AB - The location of alpha 2-adrenergic receptors has been investigated in the guinea pig kidney. We used an in vitro labeling autoradiographic technique to examine the distribution of specific [3H]clonidine binding sites with the light microscope. alpha 2-Adrenergic receptors appeared to be located predominantly on the proximal tubules. The implication of this finding for renal physiology is discussed. PMID- 6256182 TI - Discriminative stimulus effects of prototype opiate receptor agonists in monkeys. AB - This study was performed to clarify the apparent differences in the cellular substrates mediating the discriminative stimulus effects of morphine and cyclazocine. Squirrel monkeys trained to discriminate between i.m. injections of saline and either morphine (3.0 mg/kg) or cyclazocine (0.1 mg/kg) in a two-choice avoidance paradigm were tested for stimulus generalization to ethylketocyclazocine and SKF 10,047, proposed agonists of receptors mediating the effects of cyclazocine. Both drugs completely mimicked the stimulus effects of cyclazocine but not those of morphine. Naltrexone (0.3 mg/kg) produced a 3-fold shift to the right of the cyclazocine dose-response curve but did not completely block the cyclazocine-like stimulus effects of either SKF 10,047 or ethylketocyclazocine. SKF 10,047 was a competitive antagonist at the receptors mediating the stimulus effects of morphine. These data are consistent with a multiple opiate receptor model, and provide further evidence that the stimulus effects of morphine and cyclazocine are subserved by different cellular substrates. PMID- 6256183 TI - Response of a dog kidney cell line (MDCK) to antidiuretic hormone (ADH) with special reference to activation of protein kinase. PMID- 6256184 TI - Morphological changes in Ehrlich ascites tumor cells during the cell fusion reaction with HVJ (Sendai Virus). I. Alterations of cytoplasmic organelles and their reversion. PMID- 6256185 TI - Guinea pig pancreatic acini prepared with purified collagenase. PMID- 6256186 TI - Cell cycle-dependent expression of surface antigens in murine T-lymphoma cells. II. Murine leukemia virus gp70 increases in S phase. PMID- 6256187 TI - Retinoids and cultured human fibroblasts. Effects on cell growth and presence of cellular retinoic acid-binding protein. PMID- 6256188 TI - The interaction between Sendai virus and cell membranes. A quantitative analysis of 125I-sendai virus particles' association with human red blood cells. PMID- 6256189 TI - Retinoic acid-induced modifications in the growth and cell surface components of a human carcinoma (HeLa) cell line. PMID- 6256190 TI - ESR studies on membrane fluidity of Chinese hamster ovary cells grown on microcarriers and in suspension. PMID- 6256191 TI - Prolyl hydroxylase activity during sea urchin development. PMID- 6256192 TI - delta 9-Tetrahydrocannabinol transport in rabbit eyes. PMID- 6256193 TI - Distribution of beta-adrenergic receptors and isoproterenol-stimulated cyclic AMP formation in monkey iris and ciliary body. PMID- 6256194 TI - SV40-transformed hamster lens epithelial cells: a novel system for the isolation of cytoskeletal messenger RNAs and their translation products. PMID- 6256195 TI - Fine structure of lentoid bodies derived from normal and cataractous mouse lenses. PMID- 6256196 TI - Studies on experimental cataracts induced by ionophores: in vitro effects of nigericin and valinomycin on the lenses in mice. PMID- 6256197 TI - Effects of terbutaline, a beta 2-adrenergic agonist, on the membrane potentials of innervated and denervated fast- and slow-twitch muscles. PMID- 6256198 TI - Cyclic AMP and growth regulation in rat glioma cells in tissue culture. PMID- 6256199 TI - Nonlinearity in the generation of antidromic activity during evoked cortical activity. PMID- 6256200 TI - Dopamine depletion slows retinal transmission. PMID- 6256201 TI - Alanine: Glutamate ratios as an index of reversibility of cerebral ischemia in gerbils. PMID- 6256202 TI - The effect of cyclic AMP on dog renal function. AB - The infusion of dibutyryl-cyclic AMP into the dog renal artery in vivo leads to diuresis, natriuresis and glucosuria. Addition of the nucleotide to the incubation medium bathing dog renal cortex slices in vitro causes inhibition of p amino-hippurate accumulation and stimulation of glycine and beta-methyl-glucoside transport. The results are interpreted in terms of the development of a blood lumen flux of sodium and water in the renal proximal tubule, analogous to that seen in the intestine. PMID- 6256204 TI - [Effect of suloctidil on plasma viscosity in rats on an atherogenic diet]. PMID- 6256205 TI - [Influence of naloxone on the activating effect on emotionally positive brain systems of substances that induce dependence]. AB - Influence of naloxone on emotionally positive reactions facilitation produced by drugs with a dependence potential has been studied in rats. Lateral hypothalamic self-stimulation activated by heroin dropped to the initial level or was depressed. Some of the animals showed symptoms of opiate withdrawal. The effects of cocaine and amphetamine remained unchanged after the blockade of opiate receptors. Naloxone exerted a partial antagonistic action toward the activation of reward after diazepam and pentobarbital administration. PMID- 6256203 TI - Evidence against a role of (Na+ + K+)-ATPase in the alpha-adrenoceptor mediated positive inotropic effect of phenylephrine. AB - Phenylephrine (0.1-100 microM) in the presence of 1 microM propranolol increased the force of contraction in electrically driven papillary muscles from cats. This presumably alpha-adrenoceptor mediated positive inotropic effect of phenylephrine occurred without any influence on (Na+ + K+)-ATPase activity. PMID- 6256206 TI - [Effect of pharmacological agents on the development of heat stroke]. AB - The effect of drugs on the development of excitation, thermal shock and animal survival was studied. The alpha-adrenoblockers aminazin and phentolamine, the sympatholytic dopegit, and antidepressants sapilent, teperin and nuredal prolonged the time of the onset of excitation and thermal shock, and prevented the animals' death in 50-87% of experiments. It is assumed that the sympathetic nervous system plays the leading role in the development of thermal shock. Aminazin, dopegit, sapilent, teperin and nuredal can be recommended as protectors on body exposure to high temperatures. PMID- 6256207 TI - [Sequelae of a drug block and the potential for pharmacological correction of the neuroeffector effects on the heart in reversible ischemia of varying duration]. AB - The development of local reversible ischemia of the myocardium is characterized by the stereotyped time course of changes in the heat neuromediator content: predominant increase in the noradrenalin content in the hyperkinetic stage of the disease and fall in its content with concurrent increase in the acetylcholine content in the hypokinetic stage. Cardiac function changes accordingly. Partial blockade of M-cholino- and beta-adrenoreceptors leads to impaired balance of the neuroeffector influences on the heart under irreversible ischemia. The impairment is shown by more material changes in cardiac activity as compared to those induced by concurrent switch-off of the receptors. Pharmacological correction of sympathetic neuroeffector influences by means of myoephedrine increases heart resistance to its reversible ischemic alteration. PMID- 6256209 TI - [Role of calcium ions and the participation of the mitochondria in realizing the positive inotropic action of cardiac glycosides (a review of the literature)]. PMID- 6256208 TI - [Effect of calcium, thrombin and nucleotides (ADP, cAMP, cGMP) on blood platelet glycolysis and energy metabolism]. AB - It has been shown that ADP, thrombin, calcium, cAMP and cGMP induce changes in platelet metabolism. Aggregation inducers that inhibit the glycolytic enzymes decrease the content of pyruvate and ATP in platelets. The aggregation inhibitor, cAMP increases the activity of pyruvate kinase and the content of pyruvate and ATP in platelets. Cyclic AMP does not affect the activity of pyruvate kinase but raises the level of pyruvate and diminishes the content of ATP in platelets. PMID- 6256210 TI - Effect of amphetamine and dopamine on oxygen uptake of rat brain slices in vitro. AB - Effects of d-amphetamine and dopamine on rat brain cortical slices respiration were estimated to assess whether these drugs might modify membrane (Na+ + K+) ATPase activity in intact cells as they do in isolate enzyme systems. d Amphetamine, 10(-5) M (140%), 10(-6) M (123%) 10(-7) M (131%) and 10(-7) M (129%). These results may be related to estimates of (Na+ + K+)-ATPase activity in subcellular systems. In an incubation medium containing calcium, 10(-4) M ouabain does not modify brain slices respiration, but fully antagonizes oxygen consumption increases induced by d-amphetamine or dopamine, which might thus be mediated by membrane ATPase activity. Either phenoxybenzamine, oxprenolol or halo peridol, nullify those metabolic effects of d-amphetamine and dopamine, by means of unspecific mechanisms rather than by a specific interaction at drug receptor sites. It is suggested that cell respiratory control is the final resultant of mechanisms which might be separately, and oppositely, modified by drugs. PMID- 6256211 TI - [Substances with antiviral activity. XV. Preparation and antiherpes activity of alkyl- and acylamino-dihalogenated pyrimidines and pyridines]. AB - Some dihalo-amino-pyrimidines and -pyridines were alkylated and acylated at the amino group. The resulting twenty-four compounds were then tested for their action on Herpes simplex virus infection in human HEp-2 cell cultures. Five compounds were active and 2-benzamido-3,5-dichloropyridine [(III B); Table I] showed the highest antiviral activity. PMID- 6256212 TI - A bacterial test in liquid culture for the detection of mutagenic activity of antibacterial compounds: studies with cephalosporine HR 756. AB - A detailed procedure for the short term evaluation of mutagenic activity in the Salmonella assay in liquid cultures is given for Cephalosporine HR 756. The essential steps of the test are: a) determination of absence of interference of the pKM101 plasmid present in the bacterial tester strains, b) determination of the doses of the antibiotic required to obtain a limited killing, c) introduction of appropriate controls with known mutagenic compounds active in the presence and in the absence of metabolic activation, d) segregation of mutants. Following this procedure we have determined the absence of any mutagenic activity in the liquid assay of Cephalosporine HR 756. PMID- 6256213 TI - [Substances with antiviral activity. XIII. Synthesis and in vitro activity of thiosemicarbazones of 1-benzoyl- and 1-benzyl-2-chloro-3-formylindoles]. AB - A series of 1-benzoyl- and 1-benzyl-2-chloro-3-formylindole thiosemicarbazones was synthesized and investigated for antiviral activity against vaccinia virus IHD strain and parainfluenza virus type 3, HA-I/CR-8 strain. The results confirmed the previously observed high activity against vaccinia virus of m substituted benzoyl derivatives. On the contrary, the analogous benzyl derivatives showed marginal activity; the compound (V c), however, was the most active against the parainfluenza virus. PMID- 6256214 TI - Methylaplysinopsin and other marine natural products affecting neurotransmission. AB - Methylaplysinopsin is a novel marine natural product that, after oral administration, prevented the effects of tetrabenazine in mice and rats. Methylaplysinopsin was a short-acting inhibitor of monoamine oxidase activity with greatest potency when serotonin was the substrate studied. The brain concentration of serotonin in the mouse was increased by methylaplysinopsin over the same time course as monoamine oxidase inhibition ex vivo. Methylaplysinopsin was also a weak inhibitor of the neuronal uptake of [3H]serotonin and a potentiator of the K+-induced release of [3H]serotonin from prelabeled synaptosomes. The predicted potentiation of serotonergic neurotransmission was supported by initial neurophysiological studies in an identified serotonergic pathway in the central nervous system of Aplysia. Two other studies on the pharmacology of marine natural products are reviewed. The majority of polyhalogenated monoterpenes isolated from red algae had central nervous system depressant properties. The exception is plocamadiene A, which caused, in mice, a reversible spastic paresis lasting up to 72 hours after oral administration. The severe muscle spasm was antagonized by diazepam. The final study discussed is the effect of a variety of marine natural products on the synthesis, neuronal uptake, and metabolism of GABA. Their selectivity is discussed with regard to the effects on metabolic respiration, and the correlation of neurochemical and neurophysiological effects on these marine substances. PMID- 6256215 TI - Tetrodotoxin, saxitoxin, chiriquitoxin: new perspectives on ionic channels. AB - Chiriquitoxin is a new, natural analog of tetrodotoxin, differing only in having the -CH2OH on C-6 replaced with an unidentified group of 104 mass units. On isolated frog sartorius muscle fibers, chiriquitoxin is equipotent with tetrodotoxin in blocking the Na+ channel, as shown by their identical dose response relations on the maximum rate of rise of the action potential. Chiriquitoxin additionally interferes with some K+ channels, as shown by a slowed repolarization of the action potential, a reduced steady-state membrane conductance in current-clamped fibers, and a reduced K+ current in point-voltage clamped fibers. The effects of chiriquitoxin on the Na+ and K+ channels are apparently exerted by the same molecule because high concentration of tetrodotoxin can either prevent or reverse the effects of chiriquitoxin on the K+ channel. Therefore, the receptor for tetrodotoxin-chiriquitoxin is probably not located inside the Na+ channel, but is on the outside surface of the membrane close to the orifice of the Na+ channel. The results also suggest that the Na+ and K+ channels are probably not randomly distributed throughout the membrane, but occur in clusters with some definite spatial relation to each other. From the structure of tetrodotoxin and a presumed structure of chiriquitoxin, the Na+ and K+ channels are estimated to be separated from each other by not less than 5 nor much more than 15A. The receptor for saxitoxin may be different, but partially overlapping with that for tetrodotoxin-chiriquitoxin. PMID- 6256216 TI - Pharmacology of marine natural products. Introduction. PMID- 6256217 TI - [Insulin response to glucose and arginine in patients with isolated ACTH deficiency (author's transl)]. PMID- 6256218 TI - [The long term effects of the oral converting enzyme inhibitor, captopril in hypertensive patients--the endocrinological study of its hypotensive mechanism (author's transl)]. PMID- 6256219 TI - Metabolism as a prerequisite for the porphyrinogenic action of polyhalogenated aromatics, with special reference to hexachlorobenzene and polybrominated biphenyls (Firemaster BP-6). PMID- 6256220 TI - An intestinal receptor for heme: its parital characterization. PMID- 6256221 TI - Effect of delta-aminolaevulinic acid on GABA receptor binding in synaptic plasma membranes. PMID- 6256223 TI - Cyclic AMP- and Ca2+-independent glycogen synthase kinase from dog liver. PMID- 6256222 TI - Abnormal perchlorate-induced radio-iodide loss from the thyroid gland in porphyrinopathies. PMID- 6256224 TI - Radiometric measurement of pyrophosphate in cell cultures. PMID- 6256225 TI - Insulin activates a rat liver peripheral plasma-membrane cyclic AMP phosphodiesterase by a phosphorylation mechanism. PMID- 6256226 TI - Inhibition of rat liver glucose 6-phosphatase by p chloromercuribenzenesulphonate. PMID- 6256227 TI - Stimulation of growth and cytochrome P-450 production by high glucose concentration in strains of Saccharomyces cerevisiae: direct relationship of adenosine 3':5'-cyclic monophosphate and cytochrome a + a3 concentrations. PMID- 6256228 TI - Alanine transport in relation to alanine metabolism in isolated hepatocytes from fed rats. PMID- 6256229 TI - Glucose-stimulated cyclic AMP accumulation of metabolizing homogenates of the rat islets of Langerhans. PMID- 6256230 TI - The functional development of the pathway for steroid hormone production in the adrenal of the foetal sheep. PMID- 6256232 TI - Activation by glucagon of glucose 6-phosphatase activity in the liver of the foetal guinea pig. PMID- 6256231 TI - Age-dependent changes in the processing of corticotropin-containing peptides in pituitary cells of the foetal sheep. PMID- 6256233 TI - Subcellular localization of rat liver adenosine diphosphatase. PMID- 6256234 TI - Dopaminergic inhibition of thyrotropin secretion. PMID- 6256235 TI - 2':3'-Cyclic nucleotide 3'-phosphohydrolase activity in human infant corpus callosum. PMID- 6256236 TI - The effects of adenosine 3':5'-cyclic monophosphate and selected phosphodiesterase inhibitors on incorporation of L-[U-14C]lysine into protein in rat brain and liver slices. PMID- 6256237 TI - The effect of visual deprivation on beta-adrenergic receptors in the visual centres of the rat brain. PMID- 6256238 TI - Cation-dependence of the restriction endodeoxyribonuclease EcoRI. PMID- 6256239 TI - 13C n.m.r. study of unfolding and motion in small proteins. PMID- 6256240 TI - A preliminary study of immobilized NAD pyrophosphorylase. PMID- 6256241 TI - Nuclear-magnetic-resonance study of the interaction of cytochrome c with cytochrome c peroxidase. PMID- 6256242 TI - Nuclear-magnetic-resonance studies of the methanol-induced denaturation of ferricytochrome c and ferrocytochrome c. PMID- 6256243 TI - Third-harmonic detection of electron-paramagnetic-resonance spectra: resolution of the hyperfine splitting in nitrosylated nitrite reductase from vegetable marrow (Cucurbita pepo). PMID- 6256244 TI - Activation of the zymogen of collagenase by Ehrlich-ascites-tumour-cell-surface trypsin-like enzyme. PMID- 6256245 TI - Building a community gerontological program. PMID- 6256246 TI - Intracellular levels of adenosine 3':5'-cyclic monophosphate in the dorsal iris of the adult newt, during lens regeneration. AB - The intracellular levels of adenosine 3':5'-cyclic monophosphate (cAMP) were measured in the dorsal iris of the adult newt, during the first 20 days of lens regeneration. It was found that by day 2 after lens removal there is a significant drop in the levels of cAMP. After day 2 the levels of the nucleotide increase and by day 3 they are higher than those detected on day 0. The levels of cAMP remain high up to day 8. From day 8 to day 9 there is a second drop. From day 9 to day 20 the levels of cAMP did not differ significantly from the value obtained for day 0, except for days 10, 12, and 15. The period of high levels of cAMP coincides with the period of depigmentation of iris epithelial cells, the key event of lens regeneration. PMID- 6256247 TI - The control of adrenocortical cytodifferentiation by extracellular matrix. AB - Adult rat adrenal cortical cells maintained in medium supplemented with horse serum (HS) from cohesive epithelial islands secrete large amounts of corticosterone. Such cells do not produce detectable extracellular material (ECM) and are not motile. Cultures exposed to fetal calf serum supplements (FCS) produce metachromatic ECM, modulate to a fibroblastic morphology, and become motile. Within 24 h, steroid production by these cells drop 100-fold. Cells now resemble myofibroblastic "stem" cells of the adrenal cortical capsule, and express structural and functional bimorphism by exhibiting a myofibroblastic phenotype while retaining responsiveness to adrenocorticotropic hormone (ACTH) and limited corticosteroid secreting capacity. Exposure of the myofibroblastic cells to ACTH in FCS overrides the effect of FSC: ECM disappears, steroid production increases several fold, and cells develop an epithelial morphology. The possibility that ECM produced in response to FCS may be responsible for the alteration from a highly differentiated, non-motile adrenocortical cell to a less differentiated, motile adrenocortical stem cell was investigated by inhibition studies using 6-diazo-5-oxo-L-nor-leucine (DON) and by exogenously added components of ECM. DON, a glutamine analogue, inhibited the synthesis of metachromatic ECM in FCS, and prevented the modulation to a fibroblastic morphology, onset of motility, and decrease in steroid production. Addition of hyaluronic acid, but not of chondroitin sulfate, to the epithelioid secretory cells promoted a drop in steroid production and slight alteration in morphology and movement. Both results are consistent with the possibility that metachromatic ECM production is responsible for the reversion of the steroid secretory to the myofibroblastic phenotype. This effect was mimicked by maintaining cells on polystyrene surfaces that were sulfonated to a negative charge density similar to that of ECM. This result implies that the negative charge of ECM may contribute to the expression of the adrenocortical stem cell phenotype, and that its effect is extracellular. A possible physiologic role for ECM-mediated control of adrenal cortical differentiation is proposed. PMID- 6256248 TI - Control of developmental transitions in the cyclic AMP signalling system of Dictyostelium discoideum. AB - In the first few hours after starvation, the developing cAMP secretory system in Dictyostelium discoideum has been observed to be successively in one of four states: (a) quiescent, (b) excitable (capable of relay), (c) autonomously oscillating, and (d) secreting at a high steady level. A theoretical model is presented which demonstrates that the proximal cause of the transitions between different types of behavior may be slow changes in the activities of the enzymes adenylate cyclase and phosphodiesterase. These changes affect the stability properties of the steady state admitted by the cAMP signalling system. Sustained oscillations develop when the steady state is unstable, whereas relay of cAMP signals occurs upon perturbation of a stable steady state for parameter values close to those which produce oscillations. The developmental path suggested in the adenylate cyclase-phosphodiesterase space for the sequential transitions compares with the time course observed for the synthesis of these enzymes after starvation. It is suggested that there is general significance for the understanding of differentiation in the example given of a state-point following a developmental path in parameter space, moving from one behavioral domain to another, and thereby bringing about shifts in qualitative behavior. PMID- 6256249 TI - [New electrophysiological studies in the early diagnosis of encephalopathy and peripheral neuropathy in chronic uremia]. PMID- 6256250 TI - Abnormalities of serum cholinesterase isozyme in liver cirrhosis and hepatoma (Part II). AB - The pattern of serum cholinesterase (ChE) isozyme appeared to be characteristically abnormal in liver cirrhosis and hepatoma. In liver cirrhosis an abnormal fast moving peak was observed in 92.5% of fifty three patients studied. Further, diminishing activities of ChE 3 and 4, accompanied by an emergence of weak bands with unusual rates of flow, were noted in 58.5%. The latter abnormality was always associated with the former one. The pattern in hepatoma was essentially the same with liver cirrhosis, though diversity of bands was also present in some cases. It was ascertained that these abnormalities was due to sialic acid content bound to the enzyme, but was not due to production of abnormal enzyme protein moiety. It was suggested by clinical analysis that the degree of the abnormality of the isozyme may be useful for the diagnosis and prognostic evaluation of liver cirrhosis. PMID- 6256251 TI - Hepatic gluconeogenic key enzymes in patients with hepatic cancer. AB - Key enzymes of gluconeogenesis in the liver, phosphoenolpyruvate carboxykinase [EC 4.1.1.32] and glucose-6-phosphatase [EC 3.1.3.9], were studied in patients with primary or metastatic hepatic cancer. Liver specimens for enzyme assay were obtained by necropsy performed within four hours after death. It was confirmed that both enzyme activities in rat liver preserved at 4 degrees C remained unchanged within nine hours after the removal of the tissue. Activities of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase decreased to below ten per cent of the control in neoplastic liver tissue of patients with hepatocellular carcinoma accompanied with liver cirrhosis. These two enzyme activities in cirrhotic tissue of patients with hepatocellular carcinoma were lower than those in patients merely with cirrhosis. In patients with metastatic hepatic cancer both two enzyme activities further decreased and were scarcely detected not only in neoplastic tissue but also in non-neoplastic tissue. These results show that hepatic gluconeogenesis markedly decreases in patients with primary or metastatic hepatic cancer. The biochemical analysis of the blood in hepatic cancer, decreased in blood glucose and release in immunoreactive glucagon, also suggested the suppression of gluconeogenesis. PMID- 6256252 TI - The increase in cyclic AMP content in the isolated guinea pig gastric mucosa during histamine-stimulated acid secretion. AB - Using the isolated guinea pig gastric mucosa perfused in vitro with a constant acid secretion and potential difference, the cyclic AMP (cAMP) contents in the gastric mucosa and in the serosal solution were measured during the course of acid secretion stimulated by histamine or dibutyryl cyclic AMP (db-cAMP). (1) The acid-secreting response of the gastric mucosa to histamine was reproduced by addition of db-cAMP. (2) The acid secretion stimulated by db-cAMP was not inhibited. (3) The increase in mucosal cAMP content was accompanied by histamine stimulated acid secretion. (4) The increase in the mucosal cAMP content preceded the increase in acid secretion stimulated by histamine. From these findings, it has been concluded that cAMP plays an important role in the mechanism of histamine-stimulated acid secretion, including the morphological transformation of parietal cells, although its role as the intracellular mediator of the stimuli for the hydrogen ion pump itself requires further investigation. PMID- 6256253 TI - Influence of opiates on ion transport across rabbit ileal mucosa. AB - Opiates are commonly used as antidiarrheal agents, and endogenous opioids have been demonstrated in the intestine. It seemed important therefore to investigate the effects of morphine on ion transport across intestinal mucosa. In rabbit ileum in vitro morphine (2 x 10(-5) M) induced a significant fall in potential difference and short circuit current but did not influence tissue resistance. Dextromoramide (10(-5) M), an active opiate, mimicked the action of morphine, whereas the inactive isomer levomoramide (10(-5) M) had no effect. Morphine caused a significant increase in chloride absorption, due predominantly to a decrease in the serosa to mucosa flux. No change in sodium transport was detected, but the residual ion flux, possibly representing bicarbonate secretion, was enhanced. Similar response were observed with a synthetic enkephalin analogue (Me-Tyr-D-Met-Gly-Phe-Pro-NH2); but this was more potent than morphine, a significant electrical response being observed at a concentration as low as 10( 8) M. These electrical and ion transport responses to morphine were blocked by naloxone, an effect shown to be competitive in nature. The results suggest that opiate receptors exist in rabbit ileal mucosa and that these influence electrical and ion transport changes across the mucosa. PMID- 6256255 TI - Role of calcium in antral gastrin release. AB - The role of calcium in gastrin release was investigated using rat antral organ culture. During the initial 4-h culture interval, in the absence of calcium in the culture medium, gastrin release was not different from that observed with 0.5, 1, and 2 mM calcium. However, after 6 h of culture, gastrin release with 0.5, 1, and 2 mM calcium was significantly greater than that with antral explants cultured in calcium-free media. In the presence of 1 mM calcium in the culture medium gastrin release was stimulated by dibutyryl cyclic AMP, whereas with calcium-free culture medium dibutyryl cyclic AMP was ineffective in stimulating gastrin release. Effects of ionophore A23187 on gastrin release were examined in experiments with culture medium containing no added calcium and with 2 mM calcium. The dose-response to ionophore A23187 (1.2--10 microgram/ml) with 2 mM calcium demonstrated progressive increases in culture media gastrin at 30, 60, and 120 min of culture. Maximal gastrin release occurred with 10 microgram/ml ionophore at each culture interval. Gastrin releases was not stimulated by increasing doses of ionophore when added to calcium-free organ culture media. Results of these experiments suggest that calcium is important in regulation of antral gastrin release and that dibutyryl cyclic AMP-stimulated release of antral gastrin is, at least in part, calcium-dependent. Stimulation of gastrin secretion by ionophore A23187 (in the presence of calcium) further supports the role of calcium in antral gastrin release and suggests that transport of calcium across cellular membranes is important in the coupling of secretory events in the gastrin cell. PMID- 6256254 TI - Antisecretory effects of indomethacin on rabbit ileal mucosa in vitro. AB - Prior in vivo studies have shown that indomethacin, which inhibits prostaglandin (PG) synthesis, affects fluid transport in the small bowel, enhancing spontaneous fluid absorption and reducing the amount of fluid that accumulates in response to cholera toxin and other secretory stimuli. To further explore the mechanisms involved, we determined the effects of indomethacin on ion transport, cAMP concentration, and PGE2 production in rabbit ileal mucosa in vitro. Indomethacin (1 mM), when added alone, had no significant effect on short-circuit current (either basal or glucose-stimulated), Cl fluxes, or cAMP concentration. Indomethacin did, however, inhibit the ion transport changes caused by several secretagogues: Effects of theophylline, Ca-ionophore A23187, and arachidonate were reversibly inhibited by at least 65%, whereas effects of dibutyryl cAMP, 16,16-dimethyl PGE2, cholera toxin, and heat-stable Escherichia coli enterotoxin were inhibited by about 30%. Indomethacin also inhibited the theophylline-evoked increase in cAMP concentration. Indomethacin decreased PGE2 production under basal conditions and in the presence of theophylline and A23187, which may partly explain the antisecretory action of the drug. Since arachidonate increased PGE2 release from the mucosa more than 10-fold and indomethacin did not inhibit this effect, indomethacin at high concentration (0.5-1 mM) appears to also inhibit the action of intestinal secretagogues by a prostaglandin-independent mechanism. This study also demonstrates that the antisecretory effect of indomethacin is not simply due to stimulation of an unrelated absorptive process. PMID- 6256257 TI - [A new approach to the prophylaxis and therapy of puerperal mastitis (author's transl)]. AB - The prolactin-inhibitor Bromocriptin was examined in an open study in comparison with Hexoestrol, a synthetic estrogen compound, in 31 patients with severe postpartal breast engorgement and in 38 patients with acute puerperal mastitis. In both indications a significantly faster clinical improvement was achieved with Bromocriptin. Also the incision-rate in cases of breast abscess was significantly lower in the Bromocriptin group. The inhibition of prolactin is considered the method of choice, as well in the prophylaxis as in the treatment of puerperal mastitis. PMID- 6256256 TI - Influence of papaverine on bethanechol or OP-CCK stimulation of feline colonic muscle. AB - Papaverine relaxes smooth muscle from various organ systems throughout the body. The purpose of this study was to determine the effects of papaverine on colonic smooth muscle from the transverse colon of the cat. Myoelectrical activity was recorded with monopolar glass pore electrodes. Papaverine was administered alone and simultaneously with bethanechol or the octapeptide of cholecystokinin. Higher concentrations of papaverine (10(-4) M, 10(-5) M) abolished both slow-wave activity and migrating spike bursts. Lower concentrations of papaverine (10(-6) M) had no effect on slow waves or the migrating spike burst. Bethanechol (10(-6) M) or OP-CCK (4 x 10(-9) M, 4 x 10(-10) M) stimulated spike activity (p < 0.001). Papaverine (10(-6) M had a minimal effect on the increase in spike activity that occurred after octapeptide of cholecystokinin in a concentration of 4 x 10(-10) M (p < 0.05). Papaverine had no effect on the stimulation of the colonic smooth muscle by 4 x 10(-10) M octapeptide of the colonic smooth muscle by 4 x 10(-9) M octapeptide of cholecystokinin. These studies show that (a) papaverine can inhibit smooth muscle myoelectrical activity, (b) papaverine is a potent inhibitor of cholinergic stimulation of colonic smooth muscle, but (c) papaverine has a minimal effect on octapeptide of cholecystokinin stimulation of the isolated colonic smooth muscle. PMID- 6256259 TI - [Pseudomonas aeruginosa bacteriophages with DNA structure similar to the DNA structure of Mu1 phage. II. Evidence for similarity between D3112, B3, and B39 bacteriophages: analysis of DNA splits by restriction endonucleases, isolation of D3112 and B3 recombinant phages]. AB - It is found that bacteriophages B3 and B39 specific for Pseudomonas aeruginosa have the same genome structure as previously described phage D3112. On the right (S) end of their genomes a variable non-phage DNA is located (approximately 0.9 2.5 kilobases for different phages). It is probable that this variable DNa has its origin from different regions of bacterial chromosome. In genome of one of the phages, B3 phage, such variable DNA (not more than 150 base pairs) was found on the left end of DNA molecule. Isolation of a viable B3XD3112 recombinant phage and analysis of its genome with restriction technique and with studies of homo- and heteroduplex molecules had confirmed genetical relationship of B3 and D3112. Some essential non-homology of B3 and D3112 DNAs have been found on the right ends of genomes of the phages. PMID- 6256258 TI - [Initial characteristics and isolation of bacterial mutants with altered ability to transpose Tn9]. AB - The method allowing the induction of bacterial mutations affecting Tn9 transposition from the bacteriophage genome to the Escherichia coli chromosome is described. Neither impaired ability of cells to adsorb bacteriophages, nor phage DNA degradation in the mutant cells were observed in the transposition-defective mutants isolated by the method. This led us to the conclusion that the isolated mutants were indeed defective in the transposition of Tn9. PMID- 6256260 TI - [Study of a pts-gene-linked pleiotropic mutation influencing expression of catabolyte-sensitive genes of Escherichia coli K-12]. AB - Properties of the pleiotropic mutation pts17 are described. This mutation is liked to pts1 gene, which specifies the synthesis of the enzyme I of phosphoenolpyruvate-dependent phosphotransferase system (PTS) in Escherichia coli K-12. Genetic analysis has shown that pts17 mutation is located between purC and pts1 markers and that the wild type allele pts17+ has transdominant character over the mutant allele pts17. The mutant strain J6217, isogenic to parent J62, shows normal growth properties in the minimal salt media with a number of carbohydrates used as a single carbon source. The pts17 mutations does not affect the enzyme I activity, but significantly suppresses the total PTS activity in the bacterial cell extracts. The intact mutant cells reveal the enhanced rate of accumulation and phosphorylation of alpha-methylglucoside. The pts17 bacteria show 3-fold enhanced phosphohydrolase activity with glucose-6-phosphate as substrate. It is established that pts17 mutation decreases the differential rate of the L-tryptophanase synthesis and makes the process of unductions resistant to glucose catabolite repression. It is suggested that this mutation affects the activity of the PTS factor III. One can suppose that the latter mediates the influence of ptsI and ptsH mutations upon the expression of catabolite-sensitive operons in E. coli. PMID- 6256262 TI - [Reiterated genes scattered among the chromosomes of Drosophila melangoaster with varying locations. V. Nature of self-complementary RNA sequences transcribed from chromosomal DNA]. AB - Double-stranded RNA (dsRNA) sequences were isolated from either total RNA or cytoplasmic poly(A)+RNA of Drosophila melanogaster culture cells. Virtually all dsRNA was found to be of high molecular weight (> 200 base pairs) and unable to snap back after RNA melting. Thus, it corresponds to one of dsRNA classes found in mouse cells, namely, to dsRNA-A. Three different cloned DNA fragments of D. melanogaster which hybridized to melted dsRNA were selected among 100 randomly taken. All of them efficiently bound poly(A)+RNA and high percentage of total cellular DNA. According to these and other properties, they were assigned to a group of mobile dispersed genes (mdg) of D. melanogaster. dsRNA hybridizes to all subfragments of the two mobile dispersed genes tested (mdg1 and mdg3). Thus, complete transcripts of mobile dispersed genes are present in dsRNA. In total RNA transcripts from one strand are more abundant than those from another one, dsRNA is heavily enriched in the transcripts from mobile dispersed genes as compared to total RNA or poly(A)+RNA of the cytoplasm. It has been suggested that dsRNA in D. melanogaster is formed as a result of symmetric transcription of mobile dispersed genes. At least in the cytoplasmic fraction, two complementary strands are separated in vivo and may combine during the isolation of RNA. PMID- 6256261 TI - [Relation between Escherichia coli K-12 viability and mutability and the balance between DNA and protein synthesis. III. Relation between disruptions in the balance between DNA and protein synthesis and mutagenesis and viability during thymidine deprivation of thy- cells defective with respect to recB and polA genes]. AB - The phenomenon of metabolic mutagenesis is found to be determined by stabilization of metabolic breaks in DNA chains, being linked with disbalance of intracellular synthesis of DNA and protein. The rate of metabolic mutagenesis observed in case of the DNA-protein synthesis disbalance due to thymine starvation is influenced by cell genotype. The lack of exonuclease V in recB-thy- cells decreases (reduces) the rate of metabolic mutagenesis and does not effect the viability. The lack of DNA polymerase I activity in polA-thy- cells causes a sharp increase in the metabolic mutagenesis rate and a parallel sharp drop in the survival under thymine starvation, as compared to cells with polA+thy- genotype. PMID- 6256263 TI - [Management of trophoblastic disease]. PMID- 6256264 TI - Trophoblastic disease: analysis of 342 patients. AB - The registry for trophoblastic disease in Wakayama, Japan was formed and 342 cases were analyzed. The total number of trophoblastic disease was 342 during 6 years (1972-1977). The number of hydatidiform moles, invasive moles, choriocarcinoma and transitional moles was 278 (81.3%), 28 (8.2%), 18 (5.3%) and 12 (3.5%), respectively. The greatest number of hydatidiform moles occurred in the range 25-29 years inclusive. The percentage of patients with hydatidiform moles over 45 years of age was significantly high. The incidence of malignant complications (invasive moles and choriocarcinoma) of hydatidiform moles was 16.5% in 284 molar pregnancies. The frequency of malignant complications was remarkably high in women over 40 years of age. Thus the epidemiologic study of trophoblastic disease might turn up some important data and the importance should be emphasized. PMID- 6256265 TI - Plasma cAMP in normal and abnormal human pregnancy. AB - Plasma cAMP was determined using the method of Tovey et al. in normal pregnant women with a mean concentration of 18.9 +/- 0.8 pmol/ml (x- +/- SEM). Between weeks 9-12 and 33-36 of gestation, there were two peaks, with a mean cAMP of 22.5 +/- 2.4 which were significantly increased in comparison to the other weeks of pregnancy. Significantly decreased values were found in patients with threatened abortion (weeks 12-28) which terminated in abortion (11.6 +/- 2.4; p < 0.01). In premature labor no differences were found. During therapy with fenoterol there were highly significantly increased plasma cAMP levels (48.2 +/- 2.8; p < 0.0005). During thyroid hormone therapy in euthyroid goiter, cAMP was significantly decreased (14.0 +/- 1.4; p < 0.05). 1 week after cessation of therapy a highly significant increase of cAMP was observed (38.2 +/- 6.9; p < 0.0005). There was a negative linear regression between T3 and cAMP (2p < 0.01). In pregnancy with hypertension cAMP was significantly elevated (30.5 +/- 3.8 p < 0.0005), but nearly normal under antihypertensive therapy. In pregnancy with edema only, no difference was found. Induction of labor with PGE2 alpha was followed by a decrease of plasma cAMP. PMID- 6256266 TI - Detectability of radiation damage to melanoma cells using ESR spectroscopy. A review. AB - Comparison of indirect and direct methods applicable for the examination of radiation damage to melanoma cells leads to the conclusion that the only method useful for its detection appears to be the indirect method. The paper describes the principle, examples of radiobiological applications, and perspectives of future development of a new indirect method of measuring oxygen consumption by neoplastic cells under in vitro conditions. The method is based on the use of a spin label technique. PMID- 6256267 TI - Effect of fertilizers on Taenia saginata Goeze, 1782 egg viability in vitro. AB - The effect of seven fertilizers on the viability of Taenia saginata eggs was tested in vitro. The most destructive effect was produced by lime-nitrogen, in which the eggs survived only for 24 hours in the substance and for two days in a saturated solution. In the limestone the eggs survived for three days. PMID- 6256268 TI - Gastric secretion and the use of cellular and subcellular systems in gastric research. PMID- 6256269 TI - Non-epithelial malignancies of the stomach. PMID- 6256270 TI - The role of extracellular Ca++ and islet calcium stores in the regulation of biphasic insulin release. PMID- 6256272 TI - Pancreatic islet metabolism of pyruvate and other potentiators of insulin release. Effects of starvation. PMID- 6256271 TI - Cation-activated phosphatase activities in islet cell plasma membrane preparations. AB - Pancreatic islets from rats or ob/ob mice were homogenized and fractionated either by a two-step or one-step sucrose gradient centrifugation. A plasma membrane enriched fraction was obtained at a sucrose density of about 1.10. The distribution of the plasma membrane probe 125I-wheat germ agglutinin was parallel to that of other plasma membrane markers. Hydrolysis of Mg-ATP-gamma-3Pp in rat islet membranes was of high specific activity, but was little affected by K+ and/or Na+. K+-activated, ouabain-sensitive phosphatase activities were, on the other hand, readily demonstrated in both rat and ob/ob mouse islet membranes. The K+-activated hydrolysis of organophosphate indicators were markedly inhibited by ATP. The binding of 45Ca2+ to mouse islet plasma membranes was increased by ATP. Cation transport and the interaction of Ca2+ with the islet cell plasma membrane may be dependent on phosphoryl-transfer reactions with ATP as the physiological substrate. PMID- 6256273 TI - Correlations between chanelled Na+ entry, Ca2 + fluxes and insulin release in pancreatic beta-cells. AB - The results of ion flux measurements and insulin release studies performed on isolated rat islets of Langerhans using veratridine and tetrodotoxin show that Na+ channels exist in the outer membrane of pancreatic beta-cells. From a pharmacological point of view these channels appear very similar, if not identical, to those present in nerve. The consequences of opening such channels are described and their possible involvement in the physiological regulation of insulin release discussed. PMID- 6256274 TI - Ionic mechanisms of the glucose-induced membrane potential changes in B-cells. AB - The ionic basis of the glucose-induced membrane potential changes in pancreatic B cells was investigated. The results suggest that the initial depolarization of the membrane in response to a stimulation with glucose is due to a decrease of the K permeability. This depolarization seems to open a voltage-dependent Ca channel and thereby an additional depolarization, the depolarization phase of the slow waves, is initiated. Insulin release is then triggered by the entering Ca ions. The fast spike activity may be a consequence of the exocytotic process. The polarization phase of the slow waves seems to be caused by the activity of an electrogenic Na-K-pump and a calcium-dependent increase of the K permeability. The activity of the Na-pump is considered to be regulated by the intracellular Na concentration. PMID- 6256275 TI - Niemann-Pick disease, Type C: evidence for the deficiency of an activating factor stimulating sphingomyelin and glucocerebroside degradation. AB - 1) Qualitative lipid analyses by thin-layer chromatography of 4 Niemann-Pick type C spleens confirmed sphingomyelin accumulation together with increase in the amount of glucocerebroside. 2) In the presence of crude sodium taurocholate as detergent, sphingomyelin degradation rates of normal and Niemann-Pick type C cultured fibroblasts were fairly close under standard conditions at pH 5.0. In the absence of sodium taurocholate, sphingomyelinase activity was optimal at pH 4.0. Sphingomyelinase activities of fibroblasts from two patients with Niemann Pick disease type C measured without detergent, were about 30% of that of controls. 3) Extracts from Gaucher spleen heated to 90 degrees C and devoid of sphingomyelinase activity stimulated at the optimal pH of 4.0 sphingomyelin degradation by cultured normal fibroblasts (2--4-fold, Niemann-Pick type C fibroblasts (5--9-fold), whereas similarly treated extracts from Niemann-Pick type C spleen showed no stimulation of sphingomyelin catabolism. Heated extracts from normal human spleen exhibited a smaller stimulation than that shown by Gaucher spleen. This stimulating effect could not be observed in fibroblasts from patients suffering from Niemann-Pick type B (sphingomyelinase defect). 4) Heat treated extracts of Gaucher spleen were fractionated by ion exchange chromatography, isoelectric focusing and gel filtration. The active fractions obtained by these procedures stimulated sphingomyelin as well as glucocerebroside degradation and were absent from the corresponding Niemann-Pick type C preparations. Enriched activator preparations of Gaucher spleen stimulated sphingomyelinase activity of Niemann-Pick type C fibroblasts 25--38-fold and that of normal cells 3-fold. 5) The activating factor had an isoelectric point of 4.0 and an apparent molecular weight, as estimated by gel filtration, of 25000. Treatment with pronase E abolished its activity. PMID- 6256276 TI - Characterization of two high molecular weight proteins immunoprecipitated with an antibody against rat liver cytochrome c oxidase. AB - Isolated rat hepatocytes were labelled with [35S]methionine, dissolved in Triton X-100-containing buffer, and incubated with antibodies against rat liver cytochrome c oxidase. After separation by dodecyl sulfate-gel electrophoresis the fluorogram of immunoprecipitated proteins showed two labelled bands with apparent molecular weights of 52000 and 182000. The immunological relationship of the two proteins to cytochrome c oxidase was demonstrated by immunocompetition with the isolated enzyme and with purified subunits IV-VIII. Although the precursor nature of the two described proteins for cytoplasmically synthesized subunits of cytochrome c oxidase cannot be excluded, the following observations do not support this assumption: 1) The amount of incorporated radioactivity is too high; 2) they are exclusively located with the microsomal fraction; 3) the turnover is rather slow, compared to that of known precursor proteins. PMID- 6256277 TI - Isolation and characterization of secretory vesicles from bovine neurohypophyses. AB - A procedure is described for the isolation of secretory vesicles from bovine neurohypophyses by differential centrifugation followed by density gradient centrifugation on iso-osmolal gradients of percoll/sucrose. Only negligible contamination of the secretory vesicle fraction with markers for mitochondria, microsomes and plasma membranes could be detected. The amount of Ca2-ATPase in the isolated neurohypophysial secretory vesicles was of the same low order of magnitude as that of (Na, K)-ATPase. Thin-section electromicrographs confirmed the high purity of the isolated secretory vesicle fractions, In freeze-fracture electronmicrographs, vesicle fusion was demonstrated after incubation with Ca2. As shown in dodecyl sulfate-gel electrophoresis and subsequent autoradiography secretory vesicles exhibited an endogenous phosphorylation activity. The secretory vesicles contained an average of 23.1 microgram vasopressin/mg of protein. On incubation in media differing in ionic strength, pH and Ca2 concentration the vesicles were stable for at least 1 h. PMID- 6256278 TI - Effect of phorbol ester application and other mitogenic treatments on 3',5' cyclic-nucleotide phosphodiesterase activity in mouse epidermis in vivo. AB - The effects of phorbol ester application and of other mitogenic treatments on the activity of 3',5'-cyclic-nucleotide phosphodiesterase were investigated in dorsal mouse epidermis in vivo. Local treatment with either the weak tumor promoter phorbol 12,13-dibenzoate or the strong promoter 12-O-tetradecanoylphorbol 13 acetate (TPA) increased the activity of the high affinity enzyme (Km = 4 microM). The enzymic changes began within the first hour after application, and lasted for about 5 days. maximal stimulations of approximately 300--400% were reached after 3--6 h with TPA application, whereas with phorbol dibenzoate the maximum could only be reached after 1--2 days. TPA stimulation of the enzyme depended on doses within the range of 0.2 to 20 nmol and could be completely prevented by cycloheximide, but not by 5-azacytidine, actinomycin D, 5,8,11,14 eicosatetraynoic acid or indomethacin. No evidence could be found for cAMP participation in enzyme induction. An increase in enzyme activity could also be observed after other mitogenic treatments such as local application of the weakly promoting phorbol esters C14:4-phorbol acetate ("Ti8") and 4.O-methyl-TPA, or of the non-promoting divalent cation ionophore A 23187, as well as after treatment with a depilatory cream. Skin massage or removal of the horny layer, which also stimulate mitosis, did not evoke a significant increase in enzyme activity. No apparent correlation exists between the hyperplasiogenic and tumor-promoting effectiveness of a manipulation and its effect on epidermal 3',5'-cyclic nucleotide phosphodiesterase. PMID- 6256279 TI - The role of membrane sialyl and galactosyl residues in regulation of the life time of rabbit erythrocytes. PMID- 6256280 TI - Abnormal cilia in human pancreas. PMID- 6256282 TI - Serum Gm system in liver cirrhosis and hepatoma. AB - Serum Gm polymorphism was studied in 69 patients with liver cirrhosis, in 64 with liver cirrhosis plus hepatoma, in 40 with hepatoma without evidence of cirrhosis, and in 256 controls. The distribution of Gm factors in liver patients differed from that in the control group, this difference apparently being due to the distribution in cirrhosis patients negative for HBsAg and anti-HBs. Furthermore, significantly more heterozygous Gm individuals were found in this group of patients than in the control group. Thus it appears that Gm heterozygous individuals are prone to develop cryptogenic cirrhosis under the influence of other, as yet undetermined factors. PMID- 6256283 TI - The serum growth and survival requirements of SV40-transformed 3T3 cells. AB - Simian virus 40-transformed 3T3 cells are dependent on serum for survival and growth. This growth activity can be separated on a pH 2 Sephadex G100 column into two fractions: a high molecular weight activity and a low molecular weight substance that has recently been characterized as containing as its major agent, biotin. To replace the remainder of the serum requirement, hormones and other growth factors were tested. Both insulin at high, nonphysiological concentrations (200 to 500 ng/ml) and transferrin (5 X 10(-8) M) stimulate the growth rate in low serum medium (0.3% v/v bovine calf serum DME) individually and, when added together, are nearly as growth enhancing as 10% serum. The need for the residual serum in this medium can be eliminated by the use of crystalline trypsin during trypsinization. Under these serum-free conditions, biotin and transferrin supplementation provide for moderately good growth (20 to 30 hr population doubling time, 1 X 10(6) cells/3.2-cm dish final cell density). Insulin addition further stimulate the growth rate (16 to 20 hr) and the final density (1.5 X 10(6) cells). Although the protein growth factors, EGF (0.5 to 1.0 ng/ml) and FGF (4 to 10 ng/ml), also appear to enhance growth individually and additively, their effects are slight and very variable. Nevertheless, the complete serum-free medium (DME supplemented with biotin, transferrin, insulin, EGF, and FGF) yields growth comparable but still inferior to 10% serum supplementation (14-versus 12 hr population doubling time, 1 to 2 X 10(6) versus 2 to 3 X 10(6) cells final cell density). PMID- 6256284 TI - Essential amino groups of polymyxin B. PMID- 6256285 TI - Inhibitory effect of certain metal ions on the production of superoxide radical by Nishikimi's reaction. PMID- 6256286 TI - Effects of neonatal protein undernutrition on rat brain phosphoinositides. PMID- 6256287 TI - The nature of host-cell herpes-simplex virus interactions(s) that renders cells susceptible to virus-specific cytotoxic T cells. PMID- 6256288 TI - Preliminary report on serogrouping of Indian strains of Clostridium perfringens type A. PMID- 6256281 TI - Sequence organization of animal nuclear DNA. AB - Animal nuclear genomes contain DNA sequences of various degrees of repetition. These sequences are organized in highly ordered fashions; repetitive and nonrepetitive sequences either alternate in short periods, i.e., short [0.2-0.4 kilobases (kb) long] repeats are flanked by nonrepetitive sequences less than 2 kb long, or in longer periods, with repetitive and/or nonrepetitive sequences extending for several kilobases. There are two main categories of genome organization, namely those exhibiting short-period interspersion and those that do not. There are arguments for and against a regulatory role of short interspersed repetitive sequences. Besides the merely 'statistical' kinetic approach by conventional reassociation kinetics, sequence organization has been studied by restriction endonuclease mapping and nucleotide sequencing. Such studies have revealed some general features of the organization of the eukaryotic gene and its transcripts, namely possible 'promoters', 'leaders', 'introns', 'exons', 'flanking sequences', 'caps', ribosome-binding sites, and poly(A) sequences. This paper discusses how these elements of a gene might serve regulatory roles in its expression. PMID- 6256289 TI - "Coxsackie virus in diabetes mellitus". PMID- 6256290 TI - Chondroid syringoma: benign mixed tumour of skin of salivary gland type. PMID- 6256291 TI - Glomus tumour--a case report. PMID- 6256292 TI - Mechanisms of pathogenicity of anaerobic bacteria of clinical interest. AB - The host factors leading to anaerobic infection and the various models of anaerobic infection, namely direct effect of a single toxin, multiple toxin aggressin-systems, enterotoxic mechanisms, endogenous infections with non clostridial anaerobes, and synergistic infections, are reviewed. Production of carcinogens and co-carcinogens by anaerobes is also discusssed. PMID- 6256293 TI - Methods for testing antibiotic sensitivity of anaerobic bacteria. AB - Problems are still encountered in the performance and interpretation of tests of anaerobe sensitivity to antibiotics. A review of the methods currently used was carried out in order to determine factors modifying the activity of antibiotics. The sensitivity of Escherichia coli, Staphylococcus aureus and Clostridium perfringens to various drugs was tested under different conditions (including different culture media and incubation atmospheres). Gentamicin and kanamycin showed no activity in tests with brain heart infusion agar incubated anaerobically or in 10% CO2. The activity of lincomycin was much more readily influenced by test conditions than that of clindamycin. All the drugs examined except gentamicin and kanamycin showed more activity when tested in brain heart infusion agar than in Mueller Hinton blood agar. PMID- 6256294 TI - Current views in primary pulmonary cancer. AB - This chapter presents an overview of the current concepts in the diagnosis and treatment of carcinoma of the lung. Emphasis is placed on the increasing incidence, methods of detection, and diagnosis, and on the importance of staging before treatment. Best treatment recommendations are detailed by stage of disease and by presentation, with supporting evidence from institutional experience and the literature. Although surgical treatment is emphasized, other forms of management appropriate to the stage of the disease are included. The use of intraoperative irradiation to supplement surgery in the control of localized lung carcinoma is also described. PMID- 6256295 TI - Wilms tumor: a progressive study of 137 consecutive patients treated in Peru. PMID- 6256296 TI - Hormonal receptors in human neoplasia. PMID- 6256297 TI - [Methods of anesthesia in rare systemic diseases]. PMID- 6256298 TI - Complications involving neuromuscular pharmacology. PMID- 6256300 TI - Cyclazocine in the treatment of opiate addiction: a review with recommendations. AB - The use of cyclazocine, a narcotic antagonist in the treatment of opiate addiction, is reviewed. Eleven investigations which have employed cyclazocine within addiction treatment programs have led to the conclusion that cyclazocine has yet to demonstrate its therapeutic efficacy due to low patient acceptance and the difficulty in maintaining effective blocking dosages. The use of naloxone to alleviate side effects during cyclazocine induction and technological advances in implantable sustained-release devices may facilitate the effectiveness of cyclazocine treatment of opiate addiction. Experimental designs are advocated as the best method for the evaluation of narcotic treatment programs. PMID- 6256299 TI - Comparison of the effects of theophylline, prednisolone and sleep withdrawal on airway obstruction and urinary cyclic AMP/cyclic GMP excretion of asthmatic children with and without nocturnal asthma. AB - Asthmatic children suffering from nocturnal asthmatic paroxysms showed not only a reduced peak exspiratory flow rate (PEER) but also a diminished excretion of cyclic AMP (cAMP) at night. In contrast, in asthmatic children without nocturnal asthmatic attacks, neither in PEFR nor in cAMP excretion did a circadian rhythm occur. Prednisolone, theophylline, and sleep withdrawal were able to reestablish normal airway function and cAMP excretion in those patients with nocturnal bronchoconstriction. Cyclic GMP (cGMP), which has been suggested as a mediator for cholinergic mechanisms, shows the exact opposite behavior of that of cAMP. In children suffering from nocturnal asthmatic attacks, cGMP increases during the night, whereas under sleep withdrawal it decreases. Hence we propose that a reduced responsiveness of beta-adrenergic receptors as well as an increased cholinergic activity are due to nocturnal asthmatic attacks. Therapeutic interventions taking the form of increasing cAMP or decreasing cGMP levels may thus be most helpful in treating nocturnal asthma. PMID- 6256301 TI - The development of a psychiatric rehabilitation service: a two year pilot project. AB - In the history of psychiatry, one can discern conflicting trends with regard to hospitalization of people suffering from severe mental disturbances. From the beginning of the 19th century, the standard method for dealing with such people has been to take them away from their homes and work and put them in hospitals. However, since the discovery of antipsychotic drugs in the 1950's, there has developed a new movement to treat mentally disturbed people in their communities, either avoiding hospitalization altogether, or at least greatly shortening it. In many hospitals there has been a synthesis of these two trends, reflected in an upgrading of the importance of the rehabilitation function. In Shalvata Psychiatric Center, a medium-sized psychiatric hospital in Hod Hasharon, Israel, a two-year pilot project to introduce a centralized Rehabilitation Service was recently completed. The present Rehabilitation Service is based on the rehabilitation/activity therapy model in which the hospital is conceptualized as a setting in which patients may develop or recover social and vocational skills needed to function adequately in the community. It has drawn on existing, motivated staff from all mental health professions represented at the hospital, and works closely with all in-hospital wards and the day hospital. The authors discuss six areas of vocational and social rehabilitation with which the Rehabilitation Service has attempted to deal: 1. activity therapy/rehabilitation groups, 2. vocational guidance unit, 3. after-care therapeutic social club, 4. in hospital rehabilitation consultation, 5. liaison activities with community-based facilities, 6. job placement. PMID- 6256302 TI - The therapeutic club: social rehabilitation of psychiatric patients. AB - In Israel, where there exists a highly developed network of vocational rehabilitation services for discharged psychiatric patients, there are few organized programs of social rehabilitation. Accordingly, two years Shalvata Psychiatric Center, a medium-sized psychiatric hospital near Tel Aviv, opened a therapeutic social club in its satellite community clinic in the town of Raanana. The authors describe the establishment of the club and various critical facets of the on-going club experience. The club program appears to fulfill a variety of highly important therapeutic needs, and its positive results conform with those reported elsewhere. Among the rehabilitation benefits which can be attributed to such therapeutic clubs are: (1) a rich source of social stimulation, (2) the opportunity to help members improve their repertoire of social skills, (3) the separation of members from their overburdened families several evenings each week, (4) crisis intervention possibilities, and (5) continuous aftercare contact between professional mental health workers and a high risk population. One important result may be the reduction of the re-hospitalization rate among former patients who participate in the club. PMID- 6256304 TI - Free radical formation in gamma-irradiated 5-nitro-6-hydroxythymine at 77K: an electron spin resonance single crystal investigation. AB - An electron spin resonance single crystal investigation of gamma-irradiated 5 nitro-6-hydroxythymine has been carried out at 77K. The primary reduced species was identified and was shown to have the unpaired electron localized on the nitro group. NO2 radicals were identified and suggested to be formed in the decay of the primary oxidation product. A third radical which shows isotropic coupling to the methyl group was identified and is suggested to be formed by the homolytic cleavage of the C-NO2 bond. A mechanism for the radical formation is proposed. PMID- 6256303 TI - Enzymology, with applications to dermatology. PMID- 6256305 TI - The booster effect--a problem for surveillance of tuberculosis in hospital employees. PMID- 6256306 TI - Nosocomial viral infections: II. Guidelines for prevention and control of respiratory viruses, herpesviruses, and hepatitis viruses. AB - This article reviews the most likely mechanisms of transmission of the commonly encountered respiratory viruses (influenza, respiratory syncytial virus, parainfluenza, rhinovirus), herpesviruses, and hepatitis viruses, and presents the guidelines used currently for prevention and control that are in use at Strong Memorial Hospital. PMID- 6256307 TI - Calcium transport system: a comparative study in different cells. PMID- 6256308 TI - Cyclic nucleotides of cone-dominant retinas. Reduction of cyclic AMP levels by light and by cone degeneration. AB - Dark-adapted retinas or whole eyes of 13-line ground squirrels (Citellus tridecemlineatus) and western fence lizards (Sceloporus occidentalis) contain higher levels of cyclic AMP than of cyclic GMP. In these cone-dominant retinas, light reduces cyclic AMP content selectively. Freezing of dark- or light-adapted retinas or eyes also reduces cyclic AMP content, with only minimal changes in cyclic GMP levels. In addition, exposure of frozen retinas of dark-adapted ground squirrel to light results in a significant decrease in cyclic AMP content. The destruction of cone visual cells of ground squirrel retina by iodoacetic acid injection decreases the cyclic nucleotide content of the dark-adapted retina. Considering the relative loss of cyclic nucleotides from cone degeneration, we estimate that the content of cyclic AMP in visual cells of ground squirrel retina is about four times greater than that of cyclic GMP. PMID- 6256310 TI - [Sodium bicarbonate administration in neonatal metabolic acidosis]. PMID- 6256309 TI - Liver pyridoxal kinase-interaction with metal ions. AB - The binding of some mono- and divalent cations to liver pyridoxal kinase induces spectral changes. These changes in the UV absorption spectrum are consistent with our reported specificities of essential activation with K+ and NH+4 ions and low concentration of Zn2+ and much higher concentration of Mn2+. PMID- 6256311 TI - Precocious puberty in a boy with HcG-producing hepatoma. Case report. AB - This paper deals with a three-year-old male patient with sexual precocity due to a gonadotropin-producing hepatoma. Maximum levels of serum-gonadotropins were 340 muULH/ml, 430 muUHCG/ml, but only 1.4 muUFSH/ml. The level of plasma testosterone was 985 ng/dl, and of plasma delta 4-androstenedione 109 ng/dl. Gonadotropin in serum reacted like choriongonadotropin but unlike pituitary luteinizing hormone when compared in dilution tests by radioimmunoassay. Gonadotropin and androgen levels returned to normal after removal of the tumour. Histopathology showed a carcinomatous hepatoblastoma of the epithelial type with immunohistological evidence of beta-HCG production. PMID- 6256312 TI - [Recurrence of congenital mesoblastic nephroma. Case report]. AB - The congenital mesoblastic nephroma is a tumour with a low malignant potential. In this case report the clinical course as well as histological and postmortem findings of the recurrence are presented. The hitherto known recurrences of this lesion are mentioned. PMID- 6256313 TI - The value of cytochemical peroxidase reactions at the ultrastructural level in haematology. PMID- 6256314 TI - [Surgical management of pituitary adenomas with preservation of pituitary function (author's transl)]. AB - Tumors of the pituitary gland comprise a large group of the intracranial tumors. As in all tumor surgery, early diagnosis is essential for the best outcome of treatment. However, the non-functioning adenomas are often diagnosed in their later stages of development as a result of the complexity of symptoms due to a mass lesion. In contrast, hormone-secreting adenomas give early symptoms which can be supported by reliable diagnostic laboratory findings and involve the production of growth hormone, prolactin and ACTH respectively. Using the transantro-sphenoidal route, our results of surgical removal of small tumors have been excellent, and microadenomas have been treated with preservation of normal pituitary function. However, an increasing size of the tumor considerably reduces the possibility of cure. PMID- 6256315 TI - [The role of viral infection in sudden deafness (author's transl)]. AB - A series of 35 patients with various degrees of sudden deafness were investigated in regard to recent or coexistent viral infection. The virological studies included 1) viral isolation by nasopharyngeal and faecal cultures; 2) viral serology for 20 different species of virus and the Paul Bunnel test; and 3) immunocomplex tests. In only two patients could a viral infection (a viral parotitis and an adenoviral infection) be proven (i.e. 6%). Immunocomplexes were found in 15 of 22 patients. Our studies, using conventional viral diagnostic tests, do not support the belief that viral infection is a common cause of sudden deafness. To solve the question whether viral infections play a part in the occurrence of sudden deafness these diagnostic aids must be complemented with modern immunological methods. PMID- 6256316 TI - [Binaural summation of the ipsilateral and contralateral acoustic stapedius reflex (author's transl)]. AB - The binaural summation of the simultaneous contra- and ipsilateral acoustic stapedius reflexes was examined in 20 normal-hearing patients. In these patients, the effect of summation was most pronounced with subthreshold intensities. A contralateral reflex was increased by ipsilateral intensities 8 db below threshold. A reflex could also be elicited by binaural intensities which were contra- and ipsilaterally 4 db below threshold. As a result of our studies, we recommend a revision of the definition of a positive Metz-recruitment. Because of possible binaural summation effects, the absolute value of the contralateral stapedius reflex threshold should not exceed 105 db HL in spite of possible sensorineural hearing loss. PMID- 6256317 TI - Abdominal irradiation in the treatment of Wilms' tumor. PMID- 6256318 TI - Patterns of intra-abdominal relapse (IAR) in patients with Wilms' tumor who received radiation: analysis by histopathology. A report of National Wilms' Tumor Studies 1 and 2 (NWTS-1 & 2). PMID- 6256319 TI - Phase I-II study of radiolabeled antibody integrated in the treatment of primary hepatic malignancies. PMID- 6256320 TI - Radiation therapy in Wilms' tumor revisited. PMID- 6256321 TI - Independent study: a curriculum expander. PMID- 6256322 TI - Nursing students go to camp. PMID- 6256323 TI - Predictors of success in community college nursing education. PMID- 6256324 TI - Preparing nurses to teach--the charge and a response. PMID- 6256325 TI - Teaching the nursing process-practical method. PMID- 6256326 TI - Relating legalities and knowledge base to the self-governance of the nursing profession. PMID- 6256327 TI - Evaluation of a master's program by graduates and their employers. PMID- 6256328 TI - Pharmacologic management of glaucoma in the dog. PMID- 6256329 TI - Immunogenicity and safety of an inactivated vaccine for the prevention of rhinotracheitis, caliciviral disease, and panleukopenia in cats. AB - An inactivated vaccine for the prevention of feline viral rhinotracheitis (FVR), caliciviral disease, and panleukopenia has been developed. The efficacy of this vaccine for protection against FVR and caliciviral disease was assessed by vaccination of 41 cats and challenge of immunity with rrither FVR virus or feline calicivirus (FCV), strain 225. All vaccinates cats developed serum neutralizing (SN) antibody (mean SN50 1:45.5) to FVR virus, and 95% developed antibody (mean SN50 1:8.1) to FCV, strain 255. Following FVR challenge, the mean cumulative score of clinical signs was 1.1 for vaccinated cats versus 22.2 for controls. Following FCV challenge, the mean scores were 2.7 for vaccinated and 17.5 for controls. Immunogenicity of the panleukopenia fraction was demonstrated by the development of neutralizing antibody titers > 1:8 in all 21 vaccinates that were tested. PMID- 6256330 TI - Acute hemorrhagic enteritis associated with canine coronavirus and parvovirus infections in a captive coyote population. PMID- 6256331 TI - Survey for antibodies to viruses of bovine virus diarrhea, bluetongue, and epizootic hemorrhagic disease in hunter-killed mule deer in New Mexico. AB - Sera from male mule deer (Odocoileus hemionus) collected in November 1977 in Otero County, New Mexico were tested fro antibodies to bovine virus diarrhea virus (BVDV), bluetongue virus (BTV), and epizootic hemorrhagic disease virus (EHDV). Neutralizing antibodies were detected in 26 of 76 (34%) sera tested for BVDV (titer greater than or equal to 1:16). Of 46 sera tested for antibodies to BTV and EHDV, 10 (22%) and 3 (7%), respectively, were positive. Three (7%) of 46 sera were suspect (titer < 1:20) for BTV, and 18 (38%) sera were suspect (titer < 1:20) for EHDV. PMID- 6256332 TI - Poxvirus and multiple tumors in an eastern gray squirrel. AB - A moribund juvenile gray squirrel (Sciurus carolinensis) with numerous skin fibromas was submitted to the Northeastern Research Center for Wildlife Diseases. Necropsy revealed multiple firm white nodules in the lungs. On histologic examination, in addition to the skin lesions, fibromatous proliferations were seen in the wall of the alimentary tract, in 1 mesenteric lymph node, and in the myocardium. Tubular adenomas were seen in the renal cortex, and the lung nodules were bronchoalveolar adenomas. Eosinophilic intracytoplasmic poxvirus inclusion bodies were seen in both the mesenchymal and epithelial tumors. PMID- 6256333 TI - Glioblastoma multiforme in a budgerigar. PMID- 6256334 TI - Avian pox in a whistling swan. PMID- 6256335 TI - Biological activity of a new class of rifamycins. Spiro-piperidyl-rifamycins. AB - The biological properties of spiro-piperidyl-rifamycins, a new class of rifamycin antibiotics, are described. In these derivatives the positions 3 and 4 have been incorporated into an imidazolyl ring bearing a spiro-piperidyl group N substituted with linear and branched aliphatic chains. The in vitro antibacterial activity against Staphylococcus aureus and Mycobacterium tuberculosis increases with the number of the carbon atoms in the linera side chain, whereas the inhibitory effect on Escherichia coli is lowered. The antibacterial activity is only marginally affected by branching of the side chain. In vivo (experimental infections of mice) the optimal therapeutic activity against M. tuberculosis is shown by compounds bearing 3 approximately 5 carbon atoms as a linear or branched side chain; in comparison with rifampicin, the potency of these derivatives is 2 approximately 3 times higher. The finding is in a good agreement with the exceptional tissue tropism, which seems to be a favourable property of this group of derivatives. PMID- 6256336 TI - Quickfit Florisil pesticide trap for use with assisted distillation technique. AB - A quickfit Florisil pesticide trap is described for use with the assisted distillation technique for the cleanup of pesticide residues in fats. Recoveries of 80--100% were obtained for 9 pesticides. No cooling is needed and there is no measurable carryover of fat from this Florisil trap. PMID- 6256337 TI - Subcellular action of Neocarzinostatin. Intracellular incorporation, DNA breakdown and cytotoxicity. AB - The subcellular site of action of a proteinaceous antitumor antibiotic neocarzinostatin (NCS) was studied using normal human lymphocytes, Epstein-Barr virus transformed lymphoblastoid cells, osmotically burst lymphoblastoid cells, and colicin E1 plasmid DNA. The rate of DNA strand break in these different types of DNA was found to be in the following order: Colicin DNA > burst cell DNA > lymphoblastoid cell DNA > normal lymphocyte DNA. Furthermore, fluorescence microscopy revealed that lymphoblastoid cells incorporated more fluorescein isothiocyanate labeled NCS than normal cells. High uptake of NCS in lymphoblastoid cells coincided with a high killing rate; low uptake of NCS in lymphocytes resulted in very little cell killing. Uptake velocity using fluorescein diacetate (FDA) also showed that the lymphoblastoid cells exhibited a higher uptake of FDA coinciding with a higher killing rate. The cell killing activity of NCS appears to be closely associated with the rate of intracellular uptake of NCS and subsequent direct degradation of DNA by the drug. This notion is reinforced by the reported finding that the dose required for DNA strand scission is only about 1/100 of that for the inhibition of cap formation. Thus DNA strand scission, rather than the cell membrane, appears to be the primary target of NCS. Enhanced incorporation of many substances is commonly observed upon transformation of cells by viruses, and our present results may provide an important clue toward the explanation of the selective toxicity toward tumor cells of NCS. PMID- 6256338 TI - Protein-lipid interaction in rhodopsin recombinant membranes as studied by protein rotational mobility and lipid alkyl chain flexibility measurements. PMID- 6256339 TI - Simple purification and properties of bovine pancreatic deoxyribonuclease I. AB - A simple purification method for pancreatic deoxyribonuclease I (DNase I) [EC 3.1.4.3] was developed by utilizing the technique of isoelectric focusing. The active protein was resolved in to at least four forms with different isoelectric points; the major components a, b, and c had isoelectric points at pH 5.2, 4.9, and 4.8, respectively, and that of the minor component d was at 4.7. The four components (a, b, c, and d) exhibited peaks similar to those observed by Salnikow et al. after phosphocellulose chromatography (A, B, C, and D). The four components were all free from RNase and protease activities and were very stable at 0-2 degrees C for at least four weeks. Further, each of the four peaks exhibited a single protein band after polyacrylamide electrophoresis. DNase I-a antibody was prepared; it was very specific for DNase I and precipitated with the other components (b, c, and d). The mode of endonucleolytic action of pancreatic DNase I-a purified from Worthington DP grade DNase I was investigated. The sedimentation patterns in neutral sucrose gradients of digest of circular duplex DNA in an early stage of hydrolysis suggested that DNase I produces single strand scissions in the initial attack in the presence of divalent metal ions. PMID- 6256340 TI - Studies on antiviral glycosides. II. Chemical modifications of the envelope of Sendai virus. AB - Treatment of Sendai virus with p-azidophenyl-6-chloro-6-deoxy-beta-D glucopyranoside (APG) caused chemical modification of the viral envelope under UV irradiation, which did not affect the hemagglutinin activity of the virus but inhibited the hemolytic activity. Also, the transfer of phospholipid from the viral envelope to chicken erythrocytes was measured using a spinlabel technique by electron spin resonance (ESR). In this experiment, the phospholipid transfer was depressed by the treatment with APG under the conditions which inhibited the hemolytic activity of the virus. These results suggest that APG bound covalently to lipid may disturb the specific interaction between the protein and the lipid of the viral envelope, resulting in the inhibition of the hemolytic activity. The effects of APG on the hemolysis and phospholipid transfer were compared with the results for the concanavalin A- and amphotericin B-treated viruses. PMID- 6256341 TI - Ordered complexes of cytochrome c fragments. Kinetics of formation of the reduced (ferrous) forms. AB - The kinetics of formation of noncovalently bound ferrous complexes derived from fragments of horse heart cytochrome c have been investigated. When the reactions are initiated by combining ferrous heme fragments with an appropriate apofragment, in the presence of 50 mM imidazole, second order rate processes are observed with rate constants essentially the same as those reported with ferric heme fragments (Parr, G. R., and Taniuchi, H. (1979) J. Biol. Chem. 254, 4836 4842). An additional, probably consecutive, kinetic process is also demonstrated. If imidazole is not present in the reaction buffer, the kinetic profiles are dramatically altered. While this is partially due to aggregation (dimerization) of the ferrous heme fragments, it can nevertheless be demonstrated that the complementation reactions with apofragments are much faster than those observed with the corresponding ferric heme fragments (in the absence of imidazole). These results reflect the effect of the oxidation state of the heme iron on the folding mechanism and, thus, the manifold nature of protein folding pathways. The rate of reduction of productive ferric complexes by sodium ascorbate was investigated and biphasic reactions were found in all cases. The data indicate an equilibrium between two forms of the ferric complexes. The results of an experiment in which the complementation of ferric (1-25)H and (23-104) was carried out in the presence of sodium ascorbate indicate that the intermediate complex (Parr, G. R., and Taniuchi, H. (1980) J. Biol. Chem. 255, 8914-8918) is not reducible by ascorbate. Thus, the increase in oxidation-reduction potential occurring on formation of the productive complex from the unbound heme fragment occurs at a late stage of the overall reaction, possibly coinciding with ligation of methionine 80 to the heme iron. PMID- 6256342 TI - Effect of adrenalectomy and aldosterone on the modulation of mineralocorticoid receptors in rat kidney. AB - Adrenalectomized rat kidney is commonly used for the study of mineralocorticoid mechanism of action in mammals. In this model, aldosterone is known to bind to two classes of binding sites: type I (mineralocorticoid) and type II (glucocorticoid). The study of the aldosterone binding in normal rat kidney requires the elimination of endogenous hormones bound to each type of receptor. Thus, a suitable technique was developed using in situ perfusion of the kidneys. The efficacy of this method was of about 85 to 90% at the level of both cytoplasm and nucleus. Aldosterone binding capacity was checked in normal rat kidney after in situ perfusion and was found to be 300 to 500% lower than in adrenalectomized rat kidney, both in cytoplasm and nuclei. Computer analysis of aldosterone binding parameters in the cytoplasm (30,000 X g supernatant) of rat kidney suggested that adrenalectomy might induce an important rise in the number of mineralocorticoid receptors (congruent to 260%). An increase in the number of glucocorticoid receptors was also observed but appeared to be lower. Aldosterone, when perfused during 24 h in adrenalectomized rats, lowered the number of type I sites to the same level as observed in normal rat kidney. This effect was fully reversible after interruption of aldosterone perfusion. These results suggested an aldosterone-induced down regulation of mineralocorticoid receptors. PMID- 6256343 TI - Topology of the hog intrinsic factor receptor in the intestine. AB - The intrinsic factor receptor was isolated from Triton X-100 extract of hog ileal mucosa using affinity chromatography on intrinsic factor bound to cobalamin Sepharose. We verified that the receptor contains two subunits, alpha and beta. The purified receptor located in the detergent micelle was radioiodinated. The alpha subunit was labeled and dissociated from the receptor. When the receptor was immobilized on intrinsic factor cobalamin-Sepharose, the part of the receptor which binds intrinsic factor evidently faces the gel and the rest faces outward. When such gel-bound pure receptor was iodinated, the beta subunit was labeled. Iodination of the micellar cobalamin-intrinsic factor receptor complex also caused labeling of the beta subunit. This was interpreted as being due to a conformational change in the receptor affected by the binding of the substrate cobalamin-intrinsic factor, exposing groups accessible to iodination. The beta subunit was found to be hydrophobic, but the alpha subunit was soluble in phosphate buffer without detergent. The receptor was liberated from intestinal mucosa by papain treatment. The enzyme seems to solubilize an intrinsic factor binding part of the receptor, apparently a part of the alpha subunit. The liberated papain-alpha was purified by affinity chromatography. In gel filtration, it seemed to occur in dimeric form, but its true Mr = 45,000, according to findings in sodium dodecyl sulfate-electrophoresis. In the light of the findings, the topology of the receptor is suggested to be as follows: the alpha subunit binding intrinsic factor faces out and the hydrophobic beta subunit faces in. PMID- 6256345 TI - Cloning, partial sequencing, and in vitro transcription of the gene for alanine tRNA synthetase. PMID- 6256344 TI - Regulation of gonadotropin receptors and gonadotropin responses in a clonal strain of Leydig tumor cells by epidermal growth factor. AB - The MA-10 line is a clonal strain of Leydig tumor cells that has receptors for human choriogonadotropin (hCG) and mouse epidermal growth factor (mEGF). These cells respond to hCG, cholera toxin, and 8-Br-adenosine 3':5'-monophosphate with increased steroid production. It is reported herein that exposure of the MA-10 cells to mEGF results in a substantial (80 to 90%) reduction in the number of hCG receptors per cell. The loss of hCG receptors is accompanied by a corresponding reduction in the ability of hCG to stimulate steroidogenesis. The steroidogenic responses to cholera toxin and 8-Br-adenosine 3':5'-monophosphate, however, are not affected. Other results presented show that mEGF is not a mitogen for these cells. PMID- 6256346 TI - Purification and substrate specificity of bovine angiotensin-converting enzyme. AB - Angiotensin-converting enzyme was solubilized from bovine lung with detergent and purified over 2300-fold to physical homogeneity by a combination of ammonium sulfate fractionation, molecular sieve chromatography, and ion exchange chromatography. The purified enzyme had an apparent molecular weight of 126,000 in both the denatured, and reduced, denatured forms as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The purified enzyme had a specific activity of 13.6 units/mg. It was inhibited by EDTA and activated by chloride ion. Chloride functioned as a nonessential activator by raising the Vmax 4.26-fold and lowering the KM 5.99-fold under saturating conditions. Under these conditions, the Vmax was 1.2 mumol/min/unit and the KM was 1.3 mM. Three series of peptides having the general structures, Hip-His-X, Hip-X-Leu, and Hip-X-His Leu were synthesized and used to examine the binding specificity and substrate specificity of the enzyme for amino acids in the COOH-terminal (P'2), penultimate COOH-terminal (P'1), and antepenultimate COOH terminal (P1) peptide positions. These studies indicated that in terms of binding specificity, the relative importance of these three positions was P'2 > P'1 > P1, while the reverse order P1 > P'1 > P'2 was observed for the relative contribution to substrate specificity. Three peptides, Hip-His-D-Leu, Hip-D-His-Leu, and Hip-D-Phe-His-Leu, were also synthesized and used to examine the stereochemical requirements of the enzyme in terms of both peptide binding and hydrolysis. Hydrolysis was found to require an L amino acid in all three positions. In contrast, all three peptides bound to the enzyme. PMID- 6256347 TI - [13C]Methylated ribonuclease A. 13C NMR studies of the interaction of lysine 41 with active site ligands. AB - A unique resonance in the 13C NMR spectrum of [13C]methylated ribonuclease A has been assigned to a N epsilon, N-dimethylated active site residue, lysine 41. The chemical shift of this resonance was studied over the pH range 3 to 11, and the titration curve showed two inflection points, at pH 5.7 and 9.0. The higher pKa, designated pKa1, was assigned to the ionization of the lysyl residue itself while the pKa of 5.7, designated pKa2, was assigned on the basis of its pKa to the ionization of a histidyl residue which is somehow coupled to lysine 41. Both pKa values are measurably perturbed by the binding of active site ligands including nucleotides, nucleosides, phosphate, and sulfate. In most cases, the alterations in pKa values induced by the ligands were larger for pKa2. The ligand-induced perturbations in pKa2 generally paralleled those reported for histidine 12, another active site residue (Griffin, J. H., Schechter, A. N., and Cohen, J. S. (1973) Ann. N. Y. Acad. Sci. 222, 693-708). The sensitivity of the N epsilon, N dimethylated lysine 41 resonance to the histidyl ionization may result from a conformational change in the active site region of ribonuclease which is coupled to the histidyl ionization. This coupling between lysine 41 and another ribonuclease residue, which has not been documented previously, offers new insight into the interrelationship between residues in the active site of this well characterized enzyme. PMID- 6256348 TI - Oxidation of arachidonic acid in micelles by superoxide and hydrogen peroxide. AB - Arachidonic acid was co-oxidized by xanthine oxidase. Both superoxide radical and hydrogen peroxide were required for oxidation, as shown by essentially complete inhibition caused by superoxide dismutase or by catalase. Pure arachidonate, free of lipid hydroperoxides, was susceptible to this co-oxidation, and the presence of lipid hydroperoxides did not accelerate the process. The role of trace metals was indicated by the stimulatory effect of EDTA-Fe and by the inhibitory effect of diethylenetriamine pentaacetate. Initiation of arachidonate co-oxidation was due to a potent oxidant generated by the interaction of H2O2 and O2- in the presence of Fe, rather than to either O2- or H2O2 per se. Hence, mannitol, a scavenger of OH ., but not of O2- or H2O2, also inhibited oxidation. Arachidonic acid autoxidation, a much slower process than xanthine oxidase co-oxidation, was barely detectable on the time scale of these observations. Unlike the co oxidation, autoxidation was autocatalytic and therefore accelerated by hydroperoxide products. Marked quantitative differences in the distribution of isomeric hydroperoxide products of enzymic co-oxidation, as compared to the autoxidation, were noted and their significance was discussed. PMID- 6256349 TI - The single tryptophan residue of human placental lactogen. Effects of modification and cleavage on biologic activity and protein conformation. AB - In order to define further the chemical features of the human placental lactogen (hPL) molecule responsible for its lactogenic activity, two derivatives of the hormone were prepared by treatment with BNPS-skatole (2-nitrophenylsulfenyl)-3 methyl-3'-bromoindolenine). At a molar ratio of reagent to hPL of 7:1, a derivative was produced in which the single tryptophan was completely oxidized. At higher ratios, a second derivative was formed in which the peptide chain was cleaved at the tryptophan residue and the two resulting fragments remained bound by the disulfide bond between Cys53 and Cys165. Oxidation of the single tryptophan resulted in reduced immunologic activity, reduced helical content as measured by circular dichroism below 240 nm, and changes in the near-UV circular dichroic spectrum, each indicating a change in the conformation of the hPL molecule. Nevertheless, this derivative retained 20% of its ability to bind to lactogenic receptors and 40 to 50% of its ability to stimulate N acetyllactosamine synthetase in vitro. Cleavage at the tryptophan was not complete, but the loss of immunologic and biologic activity was equivalent to the degree of cleavage, indicating that the cleaved derivative was completely inactive. In addition, separation of the cleaved fragments from intact hormone followed by recombination did not generate any immunologic or biologic activity. We conclude that the single tryptophan of hPL is not essential for the biologic activity of hPL. It is likely that the reduced activity associated with modification or cleavage at the tryptophan residue is due to changes in the conformation of the molecule. PMID- 6256350 TI - Gonadotropin-releasing hormone inhibits cyclic nucleotide accumulation in cultured rat granulosa cells. AB - Ovarian granulosa cells obtained from hypophysectomized, diethylstilbestrol treated rats were cultured in the presence of ovine follicle-stimulating hormone (FSH) and gonadotropin-releasing hormone (GnRH). FSH stimulated the production and accumulation of both cAMP and cGMP, as well as progesterone, during a 48-h incubation period. Addition of GnRH or an agonist analog, [D-Ala6]des-Gly10-GnRH N-ethylamide (GnRHa), did not influence the cyclic nucleotide response to FSH in the first 6 h of incubation, but caused dose-dependent inhibition of the FSH induced rise in cyclic nucleotide production from 24 to 48 h of incubation. Cellular production of both cyclic nucleotides and progesterone was decreased by GnRHa concentrations as low as 10(-12) M, with maximum inhibition at 10(-9) M GnRHa. These results suggest that the in vitro antigonadal actions of GnRH and related peptides are expressed through inhibition of cyclic nucleotide production. PMID- 6256351 TI - Periplasmic phosphatases in Salmonella typhimurium LT2. A biochemical, physiological, and partial genetic analysis of three nucleoside monophosphate dephosphorylating enzymes. AB - Three periplasmic nucleoside monophosphate-splitting phosphatases from Salmonella typhimurium, 2':3'-cyclic nucleotide 2'-phosphodiesterase, nonspecific acid phosphatase I, and nonspecific acid phosphatase II, were separated by column chromatography. They are characterized with respect to their substrate specificities, Km values, pH optima, molecular weights, and sensitivity to inhibition by Pi and EDTA. Nonspecific acid phosphatase II has not been reported previously. The physiological roles of the various phosphatases are assessed by studies on mutant strains. Selection procedures were developed for the isolation of mutants defective in the synthesis of one or more of the phosphatase activities. Analysis of these mutant strains revealed that 2':3'-cyclic nucleotide 2'-phosphodiesterase is the major 3'-nucleotide dephosphorylating activity, and nonspecific acid phosphatase II is most active against 5' nucleotides at concentrations below 1 mM. Triple mutants, lacking all periplasmic nucleotide-splitting activities, are viable. Regulatory mutants with elevated levels of nonspecific acid phosphatase II activity were isolated. The gene for 2':3'-cyclic nucleotide 2'-phosphodiesterase (pde) was located between purA and argI at 135 min on the S. typhimurium linkage map. PMID- 6256353 TI - The effect of oligosaccharide chains of different sizes on the maturation and physical properties of the G protein of vesicular stomatitis virus. AB - The envelope glycoprotein, G, of vesicular stomatitis virus (VSV) is initially glycosylated by the en bloc transfer of Glc3Man9GlcNAc2 oligosaccharides to 2 specific asparagine residues in the nascent polypeptide chain. We carried out in vivo and in vitro studies to determine whether the size of the oligosaccharide chains on two related but different G proteins can affect their ability to fold correctly. For the in vivo studies we used a mutant lymphoma cell line, Thy-1-e, which transfers the truncated oligosaccharide, Glc3Man5GlcNAc2, to nascent polypeptides. The growth of VSV in these cells was temperature-sensitive compared to that in parental Thy-1+ cells, and VSV (San Juan) was more affected than VSV (Orsay). These results are congruous with our previous observation that in the absence of glycosylation virus assembly is temperature-sensitive and VSV (San Juan) is inhibited more than VSV (Orsay). To examine the effect of oligosaccharide size on the properties of the G protein in vitro we treated G proteins containing either Man8GlcNAc2 or Man5GlcNAc2 oligosaccharide chains with guanidine hydrochloride and measured their ability to refold using an in vitro aggregation assay. The San Juan G protein with Man5GlcNAc2 oligosaccharides aggregated at 40 degrees C but not at 30 degrees C. The Orsay G protein with Man5GlcNAc2 oligosaccharides and both proteins containing Man8GlcNAc2 oligosaccharides did not aggregate at either temperature. We conclude that the size of the oligosaccharides present on the folding G protein can be crucial in attaining a proper conformation, and the extent of their effect depends on the primary structure of the polypeptide. PMID- 6256352 TI - Receptor-dependent uptake of human chylomicron remnants by cultured skin fibroblasts. AB - Human chylomicrons were isolated from plasma from a subject with familial hypertriglyceridemia and converted to chylomicron remnants by incubation with postheparin plasma. The interaction of these apolipoprotein E-containing, cholesterol-rich human chylomicron remnants with cultured skin fibroblasts was studied. Chylomicron remnants were internalized by skin fibroblasts as a unit, mainly via the low density lipoprotein (LDL)-receptor pathway, resulting in increased cell cholesterol content. After entering the fibroblast, chylomicron remnants stimulated cholesterol esterification, suppressed 3-hydroxy-3 methylglutaryl coenzyme A reductase activity, and down-regulated LDL receptor activity similar to the action of LDL. As a function of increasing lipolysis, remnant particles were progressively more effectively taken up by skin fibroblasts, despite a decrease in the apolipoprotein E content per lipoprotein particle. Remnant particles produced after hydrolysis of 70 to 80% of chylomicron triglyceride increased cell cholesterol content to an amount nearly identical to that observed with LDL when the two lipoproteins were incubated at an equal cholesterol concentration. However, when incubated on the basis of equal particle number, chylomicron remnants were 2 to 3 times more effective than LDL in delivering cholesterol to the cells. These results suggest that chylomicron remnants play a role in the regulation of postabsorptive cholesterol homeostasis in nonhepatic cells, and possibly in the pathogenesis of atherosclerosis. PMID- 6256354 TI - Transcription of Simian virus 40 DNA in a HeLa whole cell extract. AB - Extracts of HeLa cells containing RNA polymerase II and other factors recognize specific sites on linear simian virus 40 (SV40) DNA for initiation of transcription. The most prominent RNA products transcribed from the early region of SV40 and th E strand are initiated at sites 0.67 and 0.655 on the SV40 map. These two RNAs are synthesized by polymerase II. Their 5' termini were positioned by sizing transcripts that extend from the initiation site to the end of the template restriction endonuclease fragment, and by S1-nuclease mapping of unlabeled RNA using DNA probes labeled at their 5' termini. The limit of resolution of mapping of 5' termini is approximately 25 nucleotides. RNAs with 5' termini at similar positions have been found during characterization of mRNAs produced in infected cells. Thus, the whole cell extract is probably initiating transcription on linear SV40 DNA in vitro at the same sites as RNAs synthesized in vivo. Two other processes frequently involved in mammalian cell mRNA biosynthesis, creation of specific 3'-terminal polyadenine tracts and RNA splicing, were not detected during the course of these studies. PMID- 6256355 TI - Effects of transformation on fibronectin gene expression using cloned fibronectin cDNA. PMID- 6256356 TI - Restriction enzyme mapping and heteroduplex analysis of the rat milk protein cDNA clones. AB - Detailed restriction enzyme maps have been determined for the three major rat casein and the fourth principal milk protein, alpha-lactalbumin, cDNA clones. Each of the milk protein genes exhibited unique and characteristic restriction enzyme sites. A comparison of the restriction enzyme maps of the three rat caseins revealed no apparent sequence homology among their gene sequences. The orientation of each cDNA gene sequence within the parent plasmid, pBR322, was determined by hybridization with a 3' specific cDNA probe synthesized from a partially hydrolyzed total poly(A) mRNA preparation following isolation by chromatography on oligo(dT)-cellulose. This technique provided a rapid procedure for determining the 5'-3' orientation of the cloned DNA sequences. Three casein clones were selected, which were in the same orientation, and were employed for a heteroduplex analysis to determine whether minor regions of homology existed within the alpha-, beta-, and gamma-casein genes. No heteroduplex formation was observed among these genes even under the low stringency conditions of hybridization employed, suggesting that considerable sequence divergence has occurred within the rat casein gene family. PMID- 6256357 TI - Adrenergic and cholinergic regulation of lung surfactant secretion in the isolated perfused rat lung and in the alveolar type II cell in culture. AB - The purpose of this study is to define the hormonal regulation of pulmonary surfactant secretion in two models, the isolated perfused rat lung and the isolated alveolar type II cell in culture. In the perfused lung, both cholinergic and adrenergic stimulation independently increased labeled disaturated phosphatidylcholine secretion, the major phospholipid component of surfactant, each by 2.3-fold. A concomitant increase in lung cGMP and cAMP concentration of 275- and 25-fold, respectively, was observed. The effect of each agonist was inhibited only by its appropriate antagonist. In alveolar type II cells in culture, both adenylate and guanylate cyclase responded to their appropriate agonists and antagonists. The release of 3H-labeled disaturated phosphatidylcholine was enhanced by beta-adrenergic but not alpha-adrenergic or cholinergic agonists. The effect of isoproterenol (10 microM) on surfactant release was seen by 2.5 min, and secretion was stimulated 2.9-fold at a half maximal concentration of 1 nM. Cyclic AMP levels were increased by 4.9-fold by isoproterenol at a half-maximal concentration of 40 nM. These results indicate that while in the perfused lung, secretion is stimulated by both adrenergic and cholinergic effectors, in the type II cell model, surfactant secretion is under only beta-adrenergic control. PMID- 6256358 TI - Mouse actin messenger RNAs. Construction and characterization of a recombinant plasmid molecule containing a complementary DNA transcript of mouse alpha-actin mRNA. PMID- 6256359 TI - Adeno-associated virus replication. The effect of L-canavanine or a helper virus mutation on accumulation of viral capsids and progeny single-stranded DNA. AB - We have studied the relationship between adeno-associated virus (AAV) DNA replication and virus particle assembly. Formation of empty or full particles and accumulation of AAV capsid proteins was prevented in the presence of the arginine analogue, L-canavanine, or when a temperature-sensitive helper adenovirus was used at the nonpermissive temperature. In each case there was a concomitant inhibition of AAV single-stranded (progeny) DNA accumulation but little or no effect upon synthesis of AAV duplex, replicating form DNA. These results indicate that AAV protein, perhaps in the form of assembled capsids, is required for AAV single-stranded progeny DNA accumulation. PMID- 6256360 TI - The in vivo regulation of rat liver 3-hydroxy-3-methylglutaryl coenzyme A reductase. Phosphorylation of the enzyme as an early regulatory response following cholesterol feeding. AB - Although substantial evidence supports the conclusion that 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase is the major regulatory enzyme in cholesterol biosynthesis, the molecular events involved in the in vivo regulation of this enzyme have remained obscure. In order to study this problem, rats received a single meal consisting of either rat chow or rat chow containing 2% cholesterol. The rats were killed 60 or 120 min after the beginning of feeding, and liver microsomes were prepared by ultracentrifugation. Two phases of inhibition of microsomal HMG-CoA reductase were observed. The first phase of inhibition, observed 60 min after the beginning of cholesterol feeding, was completely reversed by preincubation of the microsomes with purified phosphoprotein phosphatase. The second phase of inhibition, observed 120 min after the beginning of cholesterol feeding, was not reversed by phosphoprotein phosphatase. These results are consistent with the conclusion that phosphorylation of HMG-CoA reductase is the first step in a series of in vivo regulatory events which produce inactivation and ultimately degradation of the enzyme. PMID- 6256361 TI - HeLa ribosomal protein S6. Insulin and dibutyryl cyclic AMP affect different phosphopeptides. AB - Tryptic phosphopeptides from HeLa ribosomal protein S6 have been separated by chromatography, followed by electrophoresis. Three phosphopeptides were found in S6 from cells treated in vivo with dibutyryl cAMP and at least four different phosphopeptides were found from cells treated with insulin plus the essential amino acids. Only phosphoserine was found in S6 isolated from insulin-treated cells. PMID- 6256362 TI - Photoaffinity labeling of the cell surface adenosine 3':5'-monophosphate receptor of Dictyostelium discoideum and its modification in down-regulated cells. AB - The cAMP cell surface receptor of Dictyostelium discoideum amoebae was identified by the use of the photoaffinity analogue 8-N3-[32P]cAMP. Labeling by intact cells of one component, identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and autoradiography, could be specifically inhibited by the presence of nonradioactive cAMP. The component, P45 (apparent molecular weight of 45,000), was not identified on vegetative cells but was labeled with increasing intensity as cells differentiated and increased their levels of surface cAMP binding sites. Developmental mutants, starved under conditions where they do not express significant levels of cAMP binding sites, did not incorporate radioactivity into this protein. These mutants did label P45 when starved under differentiation-inducing conditions such that their levels of surface cAMP binding sites increased. P45 co-purified with the plasma membrane fraction isolated from cells to which 8-N3-[32p]cAMP had been covalently bound. Down regulated amoebae, which displayed approximately 25% of the binding activity of untreated cells, did not label P45. These cells did, however, label a new component with an apparent molecular weight of 47,000 (P47).l The appearance of this component represented the only discernible difference in labeling profile under these conditions. As in the case of P45, radioactive incorporation into P47 did not occur if the photoactivation of 8-N3-[32P]cAMP was performed in the presence of nonradioactive cAMP. PMID- 6256363 TI - The elevation of cyclic AMP concentrations in flagella-less sea urchin sperm heads. AB - Cycl AMP concentrations were elevated and acrosome reactions were induced in intact sea urchin spermatozoa by Nigericin, A23187, and pH 9.0 seawater. To determine whether or not the metabolism of cyclic AMP was being altered in sperm heads, the heads were mechanically separated from the flagella, and the flagella less heads were then isolated by differential centrifugation. The isolated heads contained 1 to 2 nmol of ATP and 1 to 2 pmol of cyclic AMP/mg wet weight and retained these concentrations for several hours if stored at 0 degrees C. The flagella-less heads also retained the mitochondria of the midpiece area. The heads retained their functional status and could be stimulated to undergo acrosome reactions (filament extension) in response to Nigericin, A23187, or pH 9.0 seawater. Furthermore, the isolated heads could activate sea urchin eggs after induction of an acrosome reaction by Nigericin or pH 9.0 seawater. The isolated heads contained appreciable adenylate cyclase, cyclic AMP phosphodiesterase, cyclic GMP phosphodiesterase, guanylate cyclase, cyclic AMP dependent protein kinase, and calmodulin. Nigericin, pH 9.0 seawater, and A23187 caused not only the induction of an acrosome reaction but also elevations of cyclic AMP in the isolated heads, and extracellular Ca2+ was an absolute requirement for both responses. At 16 degrees C, Nigericin caused elevations of cyclic AMP within 5 s, but maximal elevations were not observed until 1 min; it induced a maximal percentage of acrosome reactions by 40 s. Incubation of cells at 0 degrees C resulted in a delay of maximal acrosome reactions until between 10 and 20 min after addition of Nigericin. Under these conditions, maximal elevations of cyclic AMP were observed by 5 min, demonstrating that cyclic AMP elevations precede the complete morphological change associated with an acrosome reaction. ATP concentrations within the sperm heads declined in response to Nigericin, pH 9.0 seawater, or A23187, and its decrease also required the presence of extracellular Ca2+. The decline in ATP concentrations was slightly more rapid in the presence of rotenone, suggestive of some ATP synthetic capabilities of the isolated head preparation. 45Ca2+ uptake was increased by Nigericin elevated pH, and A23187 but was not appreciably altered by monensin. Monensin also did not cause appreciable elevations of cyclic AMP concentrations, induction of an acrosome reaction, or decreases of ATP concentrations. Here, we describe for the first time that cyclic AMP concentrations can be increased in flagella-less heads of spermatozoa and show that these changes are associated with an acrosome reaction. PMID- 6256364 TI - Enhanced chick oviduct dolichol kinase activity during estrogen-induced differentiation. AB - Crude microsomal preparations from hen oviduct catalyze the transfer of [32P]phosphate from [gamma-32P]CTP or [gamma-32P]dCTP to endogenous dolichol, forming dolichyl [32P]monophosphate. The oviduct kinase activity assayed with [gamma-32P]CTP is stimulated by divalent cations and exogenous dolichol. The enzymatic formation of dolichyl [32P]monophosphate is inhibited by dCDP and CDP, but not CMP, ADP, GDP, or UDP. The hen oviduct kinase is inhibited 50% by the addition of 38 microM CDP, but 101 microM dCDP is required for 50% inhibition. The amount of dolichol kinase activity in chick oviduct microsomes increases 3.7 fold within 10 days of estrogen administration. The hormone-induced increase in kinase activity is also observed when membranes from untreated and estrogen treated chicks are assayed in the presence of saturating levels of exogenous dolichol. The microsomal preparations from oviducts of untreated chicks and fully induced birds both exhibit an apparent Km value of 7.1 microM for CTP. An apparent Km of 14 microM has been determined for dCTP. Thus, the developmental change in dolichol kinase activity does not appear to be the result of a difference in the amount of available endogenous dolichol or an alteration in the reactive site for the nucleoside triphosphate substrate, but is probably due to an increased level of the enzyme. PMID- 6256365 TI - Vasopressin inhibition of epidermal growth factor binding to cultured mouse cells. PMID- 6256366 TI - Dephosphorylation of rabbit skeletal muscle glycogen synthase (phosphorylated by cyclic AMP-independent synthase kinase 1) by phosphatases. AB - Phosphorylation of rabbit skeletal muscle glycogen synthase by cyclic AMP independent synthase kinase 1 results in the incorporation of 4 mol of PO4/subunit. Incubation of the phosphorylated synthase with rabbit muscle phosphoprotein phosphatase brings about the hydrolysis of phosphates from all four major tryptic peptides and an increase in the synthase activity ratio from 0.01 to 0.85. Incubation of the phosphorylated synthase with calf intestinal alkaline phosphatase brings about the preferential hydrolysis of phosphates from three of the four major tryptic peptides and a slight increase in the four major tryptic peptides and a slight increase in the synthase activity ratio from 0.01 to 0.1. The phosphorylation site which is resistant to hydrolysis by calf intestinal alkaline phosphatase can be dephosphorylated by subsequent incubation with rabbit muscle phosphoprotein phosphatase. This dephosphorylation is accompanied by an increase in the synthase activity ratio to approximately 0.9. Measurements of the changes in the kinetic properties of the synthase samples dephosphorylated by alkaline phosphatase reveal that the phosphorylation sites susceptible to hydrolysis by alkaline phosphatase mainly affect the binding of glucose-6-P to the synthase. Comparison of the kinetic properties of the synthase samples dephosphorylated by alkaline phosphatase and by phosphoprotein phosphatase we find that the phosphorylation site resistant to hydrolysis by alkaline phosphatase affects both the binding of UDP-glucose and glucose-6-P to the synthase. PMID- 6256367 TI - Brain pyridoxal kinase. Mechanism of substrate addition, binding of ATP, and rotational mobility of the inhibitor pyridoxaloxime. AB - The inhibition kinetic patterns obtained when ATP and pyridoxal analogues are used as inhibitors of the reaction catalyzed by pyridoxal kinase are consistent with a rapid equilibrium random Bi Bi, in which binary complexes, i.e. enzyme . ATP and enzyme . pyridoxal, are formed in kinetically significant amounts. Protein fluorescence quenching was used to determine the dissociation constant (Kd = 25 microM) of ATP . Zn bound to the nucleotide site of the kinase. The binding of ATP to the kinase induces a conformational change which is transmitted to other areas of the macromolecule. Pyridoxaloxime, a competitive inhibitor of pyridoxal, was used as a probe of the pyridoxal-binding site. It binds to the kinase with Ki = 2 microM and displays a fluorescent decay time of 7.8 ns. Time emission anisotropy measurements yield a rotational correlation time for bound pyridoxaloxime of approximately 2 ns, which is considerably shorter than the rotational correlation time of the protein (phi = 38 ns). The fast rotation of pyridoxaloxime remains unaffected by the binding of ATP. PMID- 6256368 TI - Synthesis and biological activity of vitamin D3-sulfate. AB - Vitamin D3-3 beta-sulfate has been synthesized using pyridine sulfur trioxide as the sulfate donor. It has been shown to be pure by high performance liquid chromatography and spectral methods. Unlike previous reports, the product has been identified unambiguously as the 3 beta-sulfate ester of vitamin D3 by its ultraviolet, nuclear magnetic resonance, infrared, and mass spectra. The biological activity of vitamin D3-sulfate was then determined in vitamin D deficient rats. Vitamin D3-sulfate has less than 5% of the activity of vitamin D3 to mobilize calcium from bone and approximately 1% of the ability of vitamin D3 to stimulate calcium transport, elevate serum phosphorus, or support bone calcification. These results disprove previous claims that vitamin D3-sulfate has potent biological activity, and they further do not support the contention that vitamin D-sulfate represents a potent water-soluble form of vitamin D in milk. PMID- 6256369 TI - A spin label study of the thyroid hormone-binding sites in human plasma thyroxine transport proteins. AB - The binding site topographies of the three thyroid hormone-transporting proteins in human serum--prealbumin, thyroxine binding globulin, human serum albumin--have been studied with the aid of five spin-labeled analogs of L-thyroxine in which the distance between the phenolic hydroxyl and the nitroxide nitrogen ranged from 17 to 23 A. In the presence of prealbumin, the electron spin resonance spectrum of 3-([alpha-carboxy-4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenethyl] carbamoyl)-2,2,5,5-tetramethyl-3-pyrrolinl-yloxy-ethyl ester revealed the presence of a highly immobilized spin label. As the chain length between the thyroxyl moiety and the pyrroline ring was increased, the mobility of the nitroxide group in the prealbumin-bound labels increased. If the spin labels bind in an extended conformation, the thyroxine-binding site was estimated to be approximately 21 A in depth. This finding is consistent with the known crystal structure of prealbumin and suggests that the solution and crystal conformations of the protein are very similar. In contrast to prealbumin, the thyroxine-binding site on thyroxine-binding globulin was found to be more open and possibly deeper. Human serum albumin has two binding sites for thyroxine, one of which has a higher affinity and is deep enough to accommodate a molecule that is 23 A in length. The lower affinity site is somewhat shallower and probably wider, as thyroxine spin labels bound to this site exhibited greater mobility. PMID- 6256371 TI - Activation of glycogenolysis in neonatal liver. PMID- 6256370 TI - A biochemical genetic study of the role of specific nucleoside kinases in deoxyadenosine phosphorylation by cultured human cells. PMID- 6256372 TI - Exposure of fibrinogen receptor on human platelets by proteolytic enzymes. PMID- 6256373 TI - Characterization of cyclic AMP-resistant Chinese hamster ovary cell mutants lacking type I protein kinase. AB - A group of three mutants of Chinese hamster ovary cells (10260, 10265, and 10223) which are resistant to cyclic AMP (Gottesman, M. M., LeCam, A., Bukowski, M., and Pastan I. (1980) Somatic Cell Genet. 6, 45-61) have been characterized in this work. By genetic analysis, these mutants are all recessive and fall into two complementation groups. Cycl AMP-stimulated protein kinase activity in crude extracts of these mutants using histone as a substrate is decreased to 10 and 7% (complementation group I), and 31% (complementation group II), respectively, of the activity found in wild type extracts. The binding of cyclic [3H]AMP by extracts of all of these mutants is decreased to 30 to 50% of the binding found in wild type extracts. We have used the photoaffinity label 8-azidoadenosine 3':5'-[32P]monophosphate to label the regulatory subunits of type I and type II protein kinase in wild type and mutant extracts analyzed by DEAE-cellulose and Sephadex chromatography. We find that all three mutants lack type I cyclic AMP dependent protein kinase and have reduced amounts of type II kinase activity. The regulatory subunits of type I and type II kinase are present in both complementation groups. We conclude that type I protein kinase is not needed for normal growth of Chinese hamster ovary cells. The defect in both classes of mutants appears to be in the failure of the catalytic subunit to associate normally with its regulatory subunits. PMID- 6256374 TI - Cyclic AMP-dependent phosphorylation in intact cells and in cell-free extracts from Chinese hamster ovary cells. Studies with wild type and cyclic AMP-resistant mutants. PMID- 6256375 TI - Limulin: a C-reactive protein from Limulus polyphemus. PMID- 6256376 TI - Sites in histone H1 selectively phosphorylated by guanosine 3':5'-monophosphate dependent protein kinase. PMID- 6256377 TI - Histidine is the axial ligand to cytochrome alpha 3 in cytochrome c oxidase. AB - The nitric oxide-bound complexes of reduced yeast cytochrome c oxidase incorporated with [1,3-15N2]histidine have been investigated by EPR spectroscopy. The results of this study have allowed the unambiguous identification of histidine as the endogenous axial ligand to cytochrome alpha 3. PMID- 6256378 TI - Prevention by nicotinamide of desensitization to thyrotropin stimulation in cultured human thyroid cells. AB - The presence of 50 mM nicotinamide together with 100 milliunits/ml of TSH in the incubation medium prevented the decline in human thyroid cell cAMP from maximum, stimulated levels (15-30 min) that occurs when the cells are exposed to TSH alone. Nicotinamide in the absence of TSH did not increase thyroid cell cAMP content. TSH desensitization, and its prevention by nicotinamide, occurred in the presence or absence of 3-isobutyl-methylxanthine. 1-Methyl nicotinamide and N' methyl nicotinamide similarly prevented TSH desensitization. Recovery from TSH desensitization was prolonged and incomplete after 72 h. The presence of 50 mM nicotinamide hastened recovery from desensitization. Desensitization of the cAMP response to 10(6) M prostaglandin E1 and 1 mM adenosine was unaffected by nicotinamide. Other inhibitors of poly(ADP-ribose) polymerase activity, 5 bromouridine, 5-bromo-2'-deoxyuridine, and thymidine (all at 50 mM) completely or partially prevented TSH desensitization. Pyridoxine (50 mM) similarly prevented this phenomenon. As with dog thyroid cells, 10(-4) M cycloheximide blocked TSH desensitization. The combination of 10(-4) M cycloheximide and 50 mM nicotinamide had a synergistic effect in augmenting the thyroid cell cAMP response to TSH stimulation. PMID- 6256379 TI - Kinetic distinction between cytochromes a and a3 in cytochrome c oxidase. Rapid scanning stopped flow study of anaerobic reduction by a neutral and a negatively charged donor. AB - Anaerobic reduction of cytochrome c oxidase by 5,10-dihydro-5-methylphenazine (reduced PMS) and by sodium dithionite were studied by rapid scanning stopped flow spectrophotometry. In both cases the decay of the Soret band of the oxidized oxidase is not uniform. With reduced PMS, the reduction involves two molecules of reductant (4 electrons)/oxidase molecule. The first stage of the reduction exhibits an isosbestic point in the Soret region at 437 nm. This shifts to 428 nm in later stages of the reaction. The reduction of the oxidase by sodium dithionite is also complete and apparently involves SO2 radical. In this case the spectra show an isosbestic point at approximately 420 nm which shifts to 432 nm as the reaction proceeds. For each of the reductants the reaction is best described by three phases: the first is a second order reaction between the oxidase and the reductant, followed by two first order processes which appear to describe the intramolecular electron redistribution within the oxidase molecule. The results agree with the assignment of the Soret band of the oxidase molecule to cytochrome a3 with an absorption maximum near 410 nm and to cytochrome a which has its maximum absorption hear 430 nm. If these assignments are correct, the present data show that reduced PMS, an uncharged molecule, reacts more rapidly with cytochrome a than it does with cytochrome a3, while the negatively charged radical anion, SO2, appears to have more direct access to cytochrome a3. PMID- 6256380 TI - Proton nuclear magnetic resonance characterization of the oxidized intermediates of cytochrome c peroxidase. AB - Oxidation of cytochrome c peroxidase with hydrogen peroxide to form the initial oxidized intermediate, cytochrome c peroxidase compound I, drastically alters the proton hyperfine nmr spectrum. In contrast to studies of horseradish peroxidase, where the spectrum of horseradish peroxidase compound I is similar to that of the native protein, cytochrome c peroxidase compound I exhibits only broad resonances near 17 and 30 ppm from 2,2-dimethyl-2-silapentane-5-sulfonate. No unique resonances attributable to cytochrome c peroxidase compound II could be identified. These results define the molecular conditions for which resolved hyperfine resonances of the iron(IV) states of heme proteins may be observed when the data presented here are compared with the data from horseradish peroxidase. Oxidation of cytochrome c peroxidase while it is complexed to ferricytochrome c reveals that the heme resonances of cytochrome c are not influenced by the oxidation state of cytochrome c peroxidase. PMID- 6256381 TI - Stimulation of pituitary gonadotropin release does not require internalization of gonadotropin-releasing hormone. AB - Binding of gonadotropin-releasing hormone (GnRH, pyro-Glu1-His2-Trp3-Ser4-Tyr5 Gly6-Leu7-Arg8-Pro9-Gly-NH210) to its plasma membrane receptor is the first step leading to the release of pituitary luteinizing hormone. As in the case of other plasma membrane receptors, patching, capping, and internalization of this hormone receptor complex occurs rapidly following exposure of cultured pituitary cells to physiological levels of releasing hormone. In the present study we sought to determine whether gonadotropin release could occur under conditions which rigorously excluded internalization. A GnRH analog, D-Lys6-GnRH (to which a small quantity of [125I]iodoTyr5-D-Lys6-GnRH was added), was coupled by its epsilon amino group with an N-hydroxysuccinimide ester then, through a 10-A spacer arm, to a cross-linked agarose matrix. Exposure of the product to proteases, soaps, detergents, solvents, chaotropic agents, or cell cultures resulted in dissociation of < 0.28% of biologically active releasing hormone. The apparent potency of the immobilized analog was one-fourth that of the free form and it was still capable of evoking a full luteinizing hormone secretory response. It can, therefore, be concluded that internalization of GnRH is not required for gonadotropin release. PMID- 6256382 TI - Oxidation of reduced cytochrome c oxidase with 18O2. A search for mu-oxo-bridged metal species in the oxidized enzyme. AB - We have measured the increase in 18O content of water produced from single turnover oxidations of anerobically reduced cytochrome c oxidase with 18O2 in order to test the hypothesis that a reduced atom of oxygen, originating from dioxygen, remains bound to oxidized cytochrome c oxidase in the form of a mu-oxo bridge between two metal components when a single turnover occurs. When water samples produced by oxidizing the reduced enzyme with 18O2 were compared to natural abundance control samples obtained by oxidizing with 16O2, all of the 18O2 reduced in a single turnover could be accounted for in the form of additional H218O produced. We conclude that neither atom of the dioxygen reduced is incorporated into the enzyme as a bridge which is stable in the absence of oxidoreductive reactions on the time scale of several minutes. PMID- 6256383 TI - Affinity labeling of the ATP binding site of bovine lung cyclic GMP-dependent protein kinase with 5'-p-fluorosulfonylbenzoyladenosine. AB - Bovine lung cyclic GMP-dependent protein kinase was covalently labeled with the ATP analog, 5-p-fluorosulfonylbenzoyladenosine. The inactivation reaction was pseudo-first order. The rate of kinase sulfonation exhibited saturation kinetics indicative of a rapid reversible binding of the reagent prior to enzyme modification. The enzyme could be protected by MgATP, MgADP, and Mg adenylylimidodiphosphate but not by a synthetic peptide substrate. Cyclic GMP when bound to the kinase did not influence the rate of labeling. The reagent demonstrated competitive inhibition with respect to MgATP; the Ki was found to be 0.82 mM. Magnesium and cobalt ions when included in the reaction mixture accelerated the inactivation rate up to severalfold. Addition of basic polypeptides such as mixed histone, protamine sulfate, or poly-L-lysine HBr also markedly accelerated the sulfonation rate. Inactivation of the kinase with 5 'fluorosulfonyl[3H]benzoyladenosine resulted in a linear relationship between the residual phosphotransferase activity and the incorporation of up to 0.9 mol of reagent/mol of monomer. PMID- 6256384 TI - Structural requirements for glucagon receptor binding and activation of adenylate cyclase in liver. Study of chemically modified forms of the hormone, including N alpha-trinitrophenyl glucagon, an antagonist. AB - The ability of several chemically modified forms of glucagon to activate adenylate cyclase have been compared with their ability to displace 125I-glucagon from specific membrane binding sites. The results demonstrate that both NH2 terminal and COOH-terminal portions of the peptide, as well as the central region of the glucagon molecule, are all involved in receptor binding and subsequent activation of adenylate cyclase. Receptor binding was very sensitive to chemical modification of the polar residues of glucagon. For example, conversion of the sole lysine residue of glucagon to homoarginine resulted in over a 2-fold loss in receptor-binding affinity. Loss in ability to activate adenylate cyclase was at least as great as loss in receptor binding for all of the derivatives. In the case of derivatives modified at the COOH terminus, the loss in ability to activate adenylate cyclase correlated well with loss in receptor binding. In general, however, the loss of the ability to activate adenylate cyclase was greater than the loss in binding affinity. This difference was greatest for the derivative N alpha-trinitrophenyl glucagon where the loss in adenylate cyclase activation was about 100-fold greater than the loss in receptor binding. This derivative behaved as an antagonist to glucagon in the activation of adenylate cyclase. PMID- 6256385 TI - Regulation of liver hydroxymethylglutaryl-CoA reductase by a bicyclic phosphorylation system. PMID- 6256386 TI - Protein-lipid interactions in biological and model membrane systems. Deuterium NMR of Acholeplasma laidlawii B, Escherichia coli, and cytochrome oxidase systems containing specifically deuterated lipids. PMID- 6256387 TI - Phosphorus nuclear magnetic resonance study of membrane structure. Interactions of lipids with protein, polypeptide, and cholesterol. PMID- 6256388 TI - Investigations on myelination in vitro. Regulation of sulfolipid synthesis by thyroid hormone in cultures of dissociated brain cells from embryonic mice. AB - L-3,5,3'-Triiodothyronine (T3) has been shown to influence the synthesis of myelin-associated lipids in cultures of cells dissociated from brains of embryonic mice (Bhat, N. R., Sarlieve, L., Subba Rao, G., and Pieringer, R. A. (1979) J. Biol. Chem. 254, 9342-9344). This culture system was used in the present study to gain additional information on the regulation of the synthesis of myelin lipids by thyroid hormone. The rate of synthesis of the myelin associated sulfolipids remained drastically diminished throughout a 70-day developmental period when cells were grown in the presence of hypothyroid calf serum (T3 < 25 ng/100 ml; thyroxine (T4), 1.2 microgram/ml). However, the activity could be restored to normal levels after 72 h of exposure to deficient medium supplemented with exogenous T3. Half-maximal effects were obtained with 2 X 10(-9) M T3 and 6.25 X 10(-7) M T4. T3 does not alter the synthesis of sulfated mucopolysaccharides, which share adenosine 3'-phosphate, 5'-phosphosulfate (PAPS), as a common precursor, with sulfolipids. This observation argues against the hormone altering the entry of sulfate or the synthesis of PAPS. Rather, T3 acts by changing the activity of the glycolipid:PAPS sulfotransferase(s) in direct proportion to the concentration of T3 in the growth medium. The activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase, another myelin marker was also found to be T3 dependent. The response of sulfolipid synthesis to varying amounts of T3 was also observed in a serum-free medium, which suggests that T3 can function independently of other hormones and serum factors in exerting a relatively specific effect on the regulation of myelination. PMID- 6256389 TI - Multiple structural features are responsible for the nuclease sensitivity of the active ovalbumin gene. AB - The ovalbumin gene in chick oviduct nuclei or nucleosomes is digested preferentially by either DNase I or staphylococcal nuclease. Staphylococcal nuclease preferentially cuts between and within core particles of the oviduct ovalbumin gene; thus, the ovalbumin gene is more quickly degraded to mononucleosomes and the DNA within these monomers is digested to a nonhybridizable size significantly faster than the chicken globin gene. Mono- and oligonucleosomes generated by partial staphylococcal nuclease digestion at 0 degrees C, but not at 37 degrees C, retain equal sensitivity to DNase I. Most of this sensitivity persists when histone H1 and most of the non-histone chromosomal proteins are removed with 0.6 M NaCl. On the basis of these observations, we propose that nuclease sensitivity of the oviduct ovalbumin gene is due to covalent modifications of the core histones and that this sensitivity is amplified by interaction of other chromosomal proteins with these modified histones. PMID- 6256390 TI - Affinity purification of alpha-galactosidase A from human spleen, placenta, and plasma with elimination of pyrogen contamination. Properties of the purified splenic enzyme compared to other forms. AB - The substrate analog alpha-D-galactosylamine was synthesized, linked to 6 aminohexanoic acid, and coupled to carboxyhexyl-Sepharose. This affinity support permitted the purification of human alpha-galactosidase A (alpha-D-galactoside galactohydrolase, EC 3.2.1.22) from spleen, placenta, and plasma. When used in conjunction with conventional procedures, affinity chromatography enabled the rapid and specific purification of alpha-galactosidase A from each source. Significantly, pyrogenic endotoxins were eliminated from enzyme preparations by the use of the affinity column. Splenic alpha-galactosidase A was purified in high yield (38%) with a specific activity of 1.9 X 10(6) units/mg. The purified enzyme was a homodimer with a native molecular weight of 101,000 and a subunit weight of 49,800. The UV absorption coefficient was E280 1% = 18 and the lambda max was 282 nm. The plasma form was purified with a markedly improved yield to a specific activity (229,000 units/mg) which was 3 times greater than that achieved previously. The enzymes from plasma, spleen, and placenta were immunologically identical. The physical and kinetic properties of the purified enzymes were consistent with and confirmed previous findings. PMID- 6256391 TI - Activity of eukaryotic initiation factor 2 is modified by processes distinct from phosphorylation. I. Activities of eukaryotic initiation factor 2 and eukaryotic initiation factor 2 alpha kinase in lysate gel filtered under different conditions. PMID- 6256392 TI - In vitro synthesis of collagen prolyl hydroxylase. The newly synthesized enzyme contains two newly synthesized subunits of the alpha and beta size. PMID- 6256393 TI - Turnover of the surface proteins and the receptor for serum asialoglycoproteins in primary cultures of rat hepatocytes. AB - The turnover of plasma membrane proteins in primary rat hepatocyte cultures was examined by following the loss of polypeptides labeled in situ by lactoperoxidase catalyzed iodination using 125I and 131I. Most plasma membrane proteins had similar rates of degradation, having a half-life of approximately 85 h. By in situ labeling via lactoperoxidase-catalyzed iodination, as well as metabolically labeling cells with L-[35S]methionine, the asialoglycoprotein receptor, a plasma membrane constituent, was identified and shown to exist in three forms which were structurally related. The turnover of receptor on the cell surface was examined by following the loss of iodinated cell surface receptor, while the turnover of total cellular receptor, including both surface and internally localized receptor was assayed by following the loss of receptor labeled metabolically with [35S]methionine. The turnover rate in both cases was approximately 20 h. Receptor mediated endocytosis of asialoglycoproteins had no effect on the turnover of the plasma membrane proteins or receptor. Based on estimates of the rate of metabolism of the asialoglycoprotein ligand relative to the turnover rate of the receptor, we conclude each molecule of receptor can deliver about 1,000 molecules of ligand to the lysosome to be degraded. PMID- 6256394 TI - The primary structures of two yeast enolase genes. Homology between the 5' noncoding flanking regions of yeast enolase and glyceraldehyde-3-phosphate dehydrogenase genes. AB - Segments of yeast genomic DNA containing two enolase structural genes have been isolated by subculture cloning procedures using a cDNA hybridization probe synthesized from purified yeast enolase mRNA. Based on restriction endonuclease and transcriptional maps of these two segments of yeast DNA, each hybrid plasmid contains a region of extensive nucleotide sequence homology which forms hybrids with the cDNA probe. The DNA sequences which flank this homologous region in the two hybrid plasmids are nonhomologous indicating that these sequences are nontandemly repeated in the yeast genome. The complete nucleotide sequence of the coding as well as the flanking noncoding regions of these genes has been determined. The amino acid sequence predicted from one reading frame of both structural genes is extremely similar to that determined for yeast enolase (Chin, C. C. Q., Brewer, J. M., Eckard, E., and Wold, F. (1981) J. Biol. Chem. 256, 1370 1376), confirming that these isolated structural genes encode yeast enolase. The nucleotide sequences of the coding regions of the genes are approximately 95% homologous, and neither gene contains an intervening sequence. Codon utilization in the enolase genes follows the same biased pattern previously described for two yeast glyceraldehyde-3-phosphate dehydrogenase structural genes (Holland, J. P., and Holland, M. J. (1980) J. Biol. Chem. 255, 2596-2605). DNA blotting analysis confirmed that the isolated segments of yeast DNA are colinear with yeast genomic DNA and that there are two nontandemly repeated enolase genes per haploid yeast genome. The noncoding portions of the two enolase genes adjacent to the initiation and termination codons are approximately 70% homologous and contain sequences thought to be involved in the synthesis and processing messenger RNA. Finally there are regions of extensive homology between the two enolase structural genes and two yeast glyceraldehyde-3-phosphate dehydrogenase structural genes within the 5- noncoding portions of these glycolytic genes. PMID- 6256395 TI - The cyclic AMP-mediated induction of alkaline phosphatase in mouse L-cells. AB - A cell surface-localized glycoprotein that exhibits alkaline phosphatase activity was induced by treatment of mouse L-cell cultures with dibutyryl cyclic AMP. Treatment of cells with 1.5 mM dibutyryl cyclic AMP for a period of 7 days resulted in a approximately 2000-fold increase in the specific activity of the enzyme. Enzyme induction was dependent upon de novo RNA and protein biosynthesis since this induction was completely suppressed when actinomycin D (0.5 microgram/ml) or cycloheximide (5 microgram/ml) was administered with dibutyryl cyclic AMP. Further, the overall rates of incorporation of either [3H]glucosamine or [3H]leucine into macromolecules were identical in the presence or absence of dibutyryl cyclic AMP. Alkaline phosphatase was immunotitrated in 0.5% Triton X 100-solubilized cell extracts with antisera prepared against purified native enzyme and the results indicated that dibutyryl cyclic AMP stimulated that de novo synthesis of the enzyme. Analysis by sodium dodecyl sulfate polyacrylamide gel electrophoresis of specifically immunoprecipitated protein from cells incubated with either [35S]methionine or [6-3H]glucosamine demonstrated that dibutyryl cyclic AMP induced a 76,000-dalton glycoprotein that was characterized as alkaline phosphatase by its identity with native alkaline phosphatase that had been labeled with 32P in its active site. Electrophoretic analysis of specifically immunoprecipitated translation products from an in vitro protein synthesizing system supplemented with L-cell RNA isolated from uninduced and cAMP induced cells indicated that dibutyryl cyclic AMP induced the production of alkaline phosphatase-specific mRNA. These results suggest that dibutyryl cyclic AMP directly or indirectly influences the regulation of transcription of the alkaline phosphatase gene in L-cells. PMID- 6256396 TI - Nuclear magnetic resonance of heme protein crystals. General aspects. AB - A new technique capable of determining the static and dynamic structures of heme protein crystals is reported. It is shown that microcrystals of a variety of paramagnetic heme proteins, suspended in approximately 90% saturated (NH4)2SO4, may be perfectly aligned by an intense static external magnetic field, H0, due to the large anisotropy in the magnetic susceptibility of the protein caused by the paramagnetic center. Myoglobin from sperm whale (Physeter catodon) was isotopically enriched at the C epsilon methyl groups of methionine residues 55 and 131 with either 13C or 2H and studied in the crystalline solid state by 2H quadrupole echo and 13C-Fourier transform nuclear magnetic resonance spectroscopy. It was found that suspensions of both high (S = 5/2) and low (S = 1/2) spin ferric forms of the labeled protein were ordered, the axis of ordering being approximately perpendicular to the low temperature minimum g tensor valve, even though upper Kramers levels are populated at room temperature. The paramagnetic CoII derivative "coboglobin" showed similar ordering behavior, but the diamagnetic carboxymyoglobin was unaffected. The magnetic ordering method permits the recording of "single crystal" NMR spectra from microcrystalline arrays of proteins which cannot be prepared in large enough form (approximately 1 cm3) for single crystal NMR spectroscopy and thereby allows the resolution and assignment of numerous single atom sites in the crystalline solid state. The information from a "single crystal" NMR spectrum combined with that obtained on the crystal powder allows for the direct determination of (i) the spatial orientation of the particular labeled residue within the protein crystal and (ii) the rates and types of side chain motion. Resonances were assigned by spin label broadening experiments and by use of existing x-ray data to predict 2H-NMR spectra. This new technique opens up the possibility of determining directly the dynamic structure of protein crystals and of comparing the structures of proteins in the crystalline solid state with that in solution and is applicable to other heme proteins, e.g. catalase. PMID- 6256397 TI - Speract. Purification and characterization of a peptide associated with eggs that activates spermatozoa. AB - A low molecular weight peptide (speract) associated with sea urchin eggs has been purified to apparent homogeneity by charcoal adsorption, DEAE-Sephacel chromatography, Bio-Gel P-2 filtration, and Dowex AG 50W-X4 chromatography. Gametes from 5000 female sea urchins were required for the isolation of approximately 9 mg of the peptide. The isolated peptide is homogenous based on [3H]acetic anhydride labeling, gel filtration, and reverse phase high pressure liquid chromatography. Speract is composed entirely of neutral and acidic amino acids with glycine as the major component, and it appears to have a blocked NH2 terminus based on its insensitivity to leucine aminopeptidase, its failure to react with dansyl chloride, and its chromatographic behavior on strong cation exchange resins. Speract is a potent stimulator of sea urchin sperm oxygen consumption, causing significant increases of sperm respiration rates at concentrations as low as 10(-12) M and producing 20-fold increases of oxygen consumption at maximal concentrations of 10(-8) M. Sperm cyclic GMP and cyclic AMP concentrations are also increased by speract, but concentrations of at least 10(-10) M and 10(-9) M are required for half-maximal elevations, respectively. The peptide, purified from Strongylocentrotus purpuratus eggs, also cross-reacts with spermatozoa from Lytechnis pictus sea urchins, suggesting that speract does not show species specificity. These results represent the first report of the purification of a peptide associated with eggs that may affect spermatozoa under natural conditions. PMID- 6256398 TI - Differential phosphorylation of multiple sites in purified protein I by cyclic AMP-dependent and calcium-dependent protein kinases. AB - Protein I, a specific neuronal phosphoprotein, has previously been shown, using rat brain synaptosome preparations, to contain multiple sites of phosphorylation which were differentially regulated by cAMP and calcium. In the present study, Protein I was purified to homogeneity from rat brain and its phosphorylation was investigated using homogeneous cAMP-dependent protein kinase and a partially purified calcium-calmodulin-dependent protein kinase from rat brain. Employing various peptide mapping techniques, a minimum of three phosphorylation sites could be distinguished in Protein I; the phosphorylated amino acid of each site was serine. One phosphorylation site was located in the collagenase-resistant portion of Protein I and was the principal target for phosphorylation by the catalytic subunit of cAMP-dependent protein kinase. This site was also phosphorylated by calcium-calmodulin-dependent protein kinase. The other two phosphorylation sites were located in the collagenase-sensitive portion of Protein I. These latter sites were markedly phosphorylated by calcium-calmodulin dependent protein kinase, but not by cAMP-dependent protein kinase in concentrations sufficient to phosphorylate maximally the site in the collagenase resistant portion. Thus, the phosphorylation of purified Protein I by purified cAMP-dependent and calcium-calmodulin-dependent protein kinases provides an enzymological explanation for the regulation of phosphorylation of endogenous Protein I in synaptosome preparations by cAMP and by calcium observed previously. The studies suggest that certain of the synaptic actions of two distinct second messengers, cAMP and calcium, are expressed through the distinct specificities of cAMP- and calcium-dependent protein kinases for the multiple phosphorylation sites in one neuron-specific protein, Protein I. PMID- 6256400 TI - Separation of urinary steroids by gas-liquid chromatography on packed and mixed bed columns. AB - Gas-liquid chromatography (GLC) is one of the most widely used and effective techniques for group analysis of hormonal steroids. Packed columns with liquid phases OV-1, OV-17 and SE-30 are most often used and are most thermally stable. OV-1 methylsiloxane polymer is a non-selective phase employed for separating steroids according to their molecular weights and shapes. The selective phase OV 225 is a methylphenylpolysiloxane containing 75% of phenyl groups: it is used for further differentiation of functional groups of steroid molecules. We mixed nine parts of OV-1 (1%) and one part of OV-225 (3%) both on Gas-Chrom Q (100-120 mesh) and thus obtained a mixed-bed column, which enabled a higher degree of separation of some clinically important steroid metabolites. PMID- 6256399 TI - [Peritoneal hemorrhage following spontaneous rupture of a liver containing a hepatoma (author's transl)]. AB - Two cases of a rare complication of this tumor have been reported. A hepatoma can provoke an intra-peritoneal hemorrhage in two different ways: either by tearing through the hepatic tissue which surrounds it or by necrosis and hemorrhage of the tumor itself. This complication may be the initial symptom and may require emergency surgery. Local hemostasis if often precarious and does not resolve the underlying oncological problem. At best, survival is limited to several months. Rapid removal of the tumor seems to be the only means of prolonging survival although there is not yet much data on this in the literature. At any rate the poor general condition of the patient, the frequent multiplicity of the tumoral locations and the habitual cirrhotic nature of the rest of the liver would rule out any possible surgical removal in 90% of cases. In the remaining 10% where surgery is possible, the average survival rate is 13 months. PMID- 6256401 TI - Practical aspects of normal-phase chromatography. AB - Normal-phase chromatography in HPLC typically encompasses adsorption chromatography on silica and partition chromatography on cyano and amino bonded phases. Unique separations are provided for saccharides, isomers, steroids, and class separations of lipids and polynuclear aromatic hydrocarbons. PMID- 6256402 TI - Application of dansyl derivatization to the high pressure liquid chromatographic identification of equine estrogens. AB - The HPLC qualitative analysis of conjugated estrogens is accomplished by a two step procedure involving the formation of the corresponding dansyl derivatives. The first step involves the acid hydrolysis of the conjugated estrogens, followed by dansyl derivatization and HPLC separation of these derivatives on a liChrosorb Si-60 column with 50% (v/v) chloroform-n-heptane as the mobile phase. All of the dansyl estrogens are well separated except for the 17-keto estrogens, estrone, equilin, and equilenin. The second step, designed to detect the three 17-keto estrogens, begins with the selective sodium borohydride reduction of the conjugated 17-keto estrogens to the corresponding 17-hydroxyl compounds (the beta epimer being formed in vast predominance over the alpha-epimer), followed by acid hydrolysis, dansyl derivatization, and HPLC separation of the derivatives as in the first step. Detection of the 17-keto estrogens is possible by determining differences in peak heights between the chromatograms of the first and second analyses. The The proposed method is sensitive, the dansyl derivatives stable, and nine different estrogens can be readily identified. PMID- 6256403 TI - Thyrotropin (TSH) receptor and adenylate cyclase activity in human thyroid tumors: absence of high affinity receptor and loss of TSH responsiveness in undifferentiated thyroid carcinoma. AB - TSH receptor and adenylate cyclase activity of plasma membrane fractions of human thyroid tumors were examined. The mean (+/- SD) basal adenylate cyclase activity in normal thyroid tissues was 0.35 +/- 0.33 nmole/mg protein x 10 min. The activity rose to 280% (range, 270-310%) of basal with TSH (166 mU/ml). In adenomas, the activity rose to 600% (range, 530-650), which was significantly higher than that of normal thyroid (P < 0.005). In the differentiated carcinoma, TSH responsiveness of adenylate cyclase was heterogenous (range, 110-520), but was qualitatively similar to that of the normal thyroid. On the other hand, basal adenylate cyclase activity of undifferentiated carcinoma was significantly lower than that of normal thyroid (0.018 +/- 0.007 nmol/mg protein x 10 min; P < 0.05) and was not stimulated by TSH. LH, FSH, and ACTH did not stimulate the enzyme in either kind of carcinomas. The mean (+/- SD) of the capacity of the high affinity receptor of adenomas (0.72 +/- 0.64 pmol/mg protein) and differentiated carcinomas (0.77 +/- 0.84) was not significantly different from that of normal thyroid (0.92 +/- 0.84). The affinity constants of the receptors in these three tissues were much the same (1.6-2.4 x 10(10) M-1). On the other hand, high affinity receptor could not be detected in all of the undifferentiated thyroid carcinoma. It seems likely that the failure of adenylate cyclase to respond to TSH in undifferentiated carcinoma of the thyroid is due to an alteration at the level of the receptor site. These data suggest that growth and metabolic activity of undifferentiated carcinoma may be independent of TSH, while those of adenoma and differentiated carcinoma may be affected by TSH. PMID- 6256404 TI - Concomitant secretion of adrenocorticotropin, beta-endorphin, and gamma melanotropin from perfused pituitary tumor cells of Cushing's disease: effects of lysine vasopressin, rat median eminence extracts, thyrotropin-releasing hormone, and luteinizing hormone-releasing hormone. AB - Regulation of secretion of ACTH-, beta-endorphin-, and gamma-melanotropin-like immunoreactivities (ACTH-LI, beta-EP-LI, and gamma-MSH-LI, respectively) was studied by using a perfused Sephadex column containing dispersed pituitary tumor cells obtained from three patients with Cushing's disease. Serial dilution of the perfusion medium gave lines parallel to the standard curve in each RIA for ACTH, beta-EP and gamma-MSH, suggesting that immunoreactive materials in the medium are immunologically indistinguishable from the authentic peptides. Gel exclusion chromatography of the medium revealed the existence of ACTH, beta-lipotropin (beta-LPH), beta-EP, and their possible precursor protein. gamma-MSH-LI consists of a major peak of big gamma-MSH eluted near the elution position of beta-LPH, suggesting the entire or nearly entire N-terminal portion of the precursor molecule. The addition of lysine vasopressin and rat median eminence extracts (MEE) to the perfusion system concomitantly enhanced the release of ACTH-LI, beta EP-LI, and gamma-MSH-LI, although the dose-response relationship was clear-cut only in the case of MEE. TRH and LRH also elicited the concomitant release of these peptides in one patient, in whom combined administration of TRH and LRH significantly augmented plasma cortisol levels when studied preoperatively. The molar ratio of ACTH-LI to beta-EP-LI was approximately 1.0, whereas gamma-MSH-LI was about one fourth of ACTH-LI when compared on a weight basis. These results indicate that 1) ACTH-producing human pituitary adenomas concomitantly secrete ACTH, beta-LPH, beta-EP, and big gamma-MSH, and 2) lysine vasopressin, MEE, TRH, and LRH act directly on pituitary cells to stimulate the release of these peptides. PMID- 6256405 TI - Effects of delta 9-tetrahydrocannabinol during the follicular phase of the rhesus monkey (Macaca mulatta). AB - It is well documented in the literature that delta 9-tetrahydrocannabinol (THC) decreases serum concentrations of pituitary gonadotropins in several species. To study its effects in the menstrual cycle of regularly cycling rhesus monkeys, 2.5 mg/kg THC were administered to five animals from days 1-18 of the cycle [ovulation day in our colony, 15 +/- 1 day (mean +/- SD)]. Controls received vehicle (Tween 80 and saline) in an identical protocol. Animals were bled daily or every other day, and serum total estrogens, LH, PRL, and progesterone were determined by RIA. Serial laparoscopies were performed to visualize ovulation. Whereas animals treated with vehicle presented normal cycle lengths (26, 26, 29, 30, and 34 days), those treated with THC presented abnormal lengths (145, 76, 22, 94, and 59 days). All vehicle-treated cycles were ovulatory, while four of five THC cycles were anovulatory (P < 0.02). Five THC-treated animals were anovulatory in the posttreatment cycle. To determine the site of action of THC-induced anovulation, five animals received THC, human menopausal gonadotropin, and hCG simultaneously. All ovulated normally, as determined by laparoscopic visualization of stigma. Normal luteal phases were evidenced by normal luteal phase lengths and serum progesterone concentrations. These findings are of clinical relevance, since they were achieved with doses of THC that produce blood concentrations similar to those found in heavy marijuana users. PMID- 6256406 TI - Human plasma beta-endorphin during pregnancy, labor, and delivery. AB - beta-Endorphin immunoactivity was measured in the plasma of 50 pregnant women, 25 nonpregnant women, 19 women during labor, and 25 women at the time of vaginal delivery. Simultaneous maternal and umbilical cord plasma samples were obtained in 23 cases. Mean beta-endorphin immunoactivity in the pregnant women was 15.6 +/ 1.6 pg/ml. No significant differences in mean beta-endorphin concentration were found in the first, second, or third trimesters until after the onset of labor, and at no time during this interval did levels differ from the mean of 12 +/- 1.9 pg/ml found in nonpregnant controls. In early labor, beta-endorphin was not elevated (14.8 +/- 2.3 pg/ml), but rose in the later stages of labor (cervical dilatation, > 4 cm) to 70.3 +/- 8.2 pg/ml and peaked during delivery at 113 +/- 13.3 pg/ml. Chromatography of plasma from women at delivery, pregnant women not in labor, and nonpregnant controls to separate beta-endorphin from cross-reacting beta-lipotropin showed mean beta-endorphin to beta-lipotropin molar ratios of 0.22-0.27 in the three groups, with no significant differences among the groups. In 23 subjects in whom simultaneous maternal and umbilical cord plasma samples were obtained, there was no correlation between the beta-endorphin immunoactivity in the paired samples, supporting the concept that fetal beta-endorphin is not of maternal origin. In 13 fetal umbilical cord samples, ACTH was measured in addition to beta-endorphin immunoactivity. A close correlation (r = 0.836) was observed between the concentrations of the two peptides, suggesting that in the fetus, as in the adult, beta-endorphin and ACTH are processed in parallel from a common precursor. PMID- 6256407 TI - Hormonal and metabolic abnormalities associated with central nervous system germinoma in children and adolescents and the effect of therapy: report of 10 patients. AB - We describe the results of clinical and endocrinological investigations performed on 10 children and adolescents (5 males and 5 females) with a primary central nervous system germinoma. Eight of 10 patients were between 10-20 yr of age at the time of initial presentation. Polyuria (7 of 10) and a decrease in or cessation of linear growth (5 of 10) were the most common presenting symptoms, while only 2 of 10 patients complained of visual problems. Two patients presented with the syndrome of polyuria, adipsia, hypernatremia, profound muscle weakness, and hyperlipidemia. Initial physical exam revealed abnormal eye findings in 60%, short stature (greater than or equal to 2.5 SD) in 50%, and abnormal pubertal development in 30% of the patients. The neoplasm was located in the suprasellar hypothalamic region in 8, caudate nucleus in 1, and pineal region in 1. Biopsy performed in 7 patients revealed the classic two-cell germinoma in all cases. Assessment of endocrine function before radiotherapy documented pituitary deficits in all patients studied. Antidiuretic hormone was deficient in 8 of 10 patients and was associated with hypoadipsia in 4. GH was deficient in al patients tested (7 of 7). TSH (5 of 8), ACTH (3 of 7), and gonadotropin (1 of 1) deficiencies were also common before treatment. Plasma PRL concentrations were elevated in 5 of 8 patients, all with suprasellar tumors. The hCG values were elevated only in the patient with sexual precocity (1 of 10). Endocrine evaluation during the postirradiation period revealed additional instances of GH (1), ACTH (1), and gonadotropin (5) deficiencies. All 10 patients are alive without evidence of active disease 6 months to 10 yr after radiation therapy (4500-5100 R). Evidence of hypothalamic-pituitary dysfunction is an early and almost universal feature of central nervous system germ cell tumors. The importance of careful evaluation and follow-up of children with acquired anterior or combined anterior and posterior pituitary dysfunction for a suprasellar tumor is stressed. PMID- 6256408 TI - Silent pituitary apoplexy: subclinical infarction of an adrenocorticotropin producing pituitary adenoma. AB - A young woman developed intermittent headaches and progressive hyperpigmentation after bilateral adrenalectomy for Cushing's disease. Results of sellar polytomography were abnormal. Her plasma ACTH levels increased to 4750-7340 pg/ml and did not rise with insulin-induced hypoglycemia. Although she experienced no clinical features associated with spontaneous infarction of a pituitary tumor, plasma ACTH levels fell to 474-575 pg/ml, and hemorrhagic necrosis was found in a 5-mm chromophobe adenoma at transsphenoidal surgery. Postoperatively, ACTH levels returned to normal (51-88 pg/ml), with the rest of her anterior pituitary function remaining intact 4 yr later. Spontaneous infarction of pituitary microadenomas may be subclinical, resulting in improvement of pituitary hormone hypersecretion without impairment of other anterior pituitary hormone secretion. PMID- 6256409 TI - Effect of calcium on superoxide production by phagocytic vesicles from rabbit alveolar macrophages. AB - Phagocytic vesicles from rabbit lung macrophages produced superoxide in the presence of NADH or NADPH. At 37 degrees C, these vesicles generated 51+/-7.8 nmol O(2) (-)/min per mg protein in the presence of 0.5 mM NADPH. The apparent K(m) for NADPH and NADH (66 and 266 muM, respectively), the pH optimum for the reaction (6.9), and the cyanide insensitivity were similar to properties of plasma membrane-rich fractions of stimulated polymorphonuclear leukocytes studied by others. The activity of the phagocytic vesicles was trypsin sensitive. The specific superoxide-generating activity of macrophage phagocytic vesicles isolated from cells incubated up to 90 min with phagocytic particles remained constant. Calcium in micromolar concentrations inhibited the NADPH-dependent O(2) (-)-generating activity of phagocytic vesicles. In a physiological ionic medium (100 mM KCl, 2.5 mM MgCl(2), 30 mM imidazole-HCl, pH 6.9), a maximal inhibition of O(2) (-) generation by phagocytic vesicles of 80% was observed at 40 muM free Ca(2+). The half maximum inhibitory effect was at 0.7 muM Ca(2+). Variations of the calcium concentration resulted in rapid and reversible alterations in O(2) ( )-forming activity. Preincubation of phagocytic vesicles in the presence of EGTA rendered their O(2) (-) generation rate in the presence of NADPH insensitive to alterations in the free calcium concentration. This desensitization by low EGTA concentrations (1 mM) was not reversible by the addition of calcium either in the presence or absence of purified rabbit lung macrophage or bovine brain calmodulins. Furthermore, trifluoperazine, a drug that inhibits calmodulin-stimulated reactions, did not alter the activity or the calcium sensitivity of the superoxide-generating system of sensitive phagocytic vesicles. Peripheral plasma membrane vesicles (podosomes) prepared by gentle sonication of macrophages possessed on O(2) (-)-generating system with similar properties to those of phagocytic vesicles. We conclude that the activated O(2) ( )-generating system of rabbit lung macrophages has its initial localization in the plasmalemma and undergoes subsequent internalization into phagocytic vesicles, where it can function for prolonged periods of time. Calcium at concentrations likely to exist in macrophage cytoplasm exerts a regulatory effect on the activated system. PMID- 6256411 TI - Monocyte-mediated serum-independent damage to hyphal and pseudohyphal forms of Candida albicans in vitro. AB - Human peripheral blood monocytes attached to Candida albicans hyphae in the absence of serum and damaged the hyphae without completely ingesting them. Attachment and damage was not augmented by the addition of serum. Damage to hyphae was quantitated by a previously developed metabolic assay that measured leukocyte-induced reduction in uptake of [(14)C]cytosine by the hyphae. Use of cells from patients with hereditary disorders of leukocyte function, chronic granulomatous disease, and myeloperoxidase deficiency indicated that myeloperoxidase-independent and nonoxidative mechanisms could sometimes damage hyphae where oxidative mechanisms were impaired. Damage to hyphae by normal monocytes was inhibited by concentrations of sodium azide and sodium cyanide that primarily affect myeloperoxidase activity, as well as by halide-free conditions, catalase, and putative antagonists of hypochlorous acid or singlet oxygen. Iodination of hyphae, a myeloperoxidase and hydrogen peroxide-dependent process of monocytes, was similarly inhibited by sodium azide, sodium cyanide, and catalase. Under anaerobic conditions, damage to hyphae was reduced by 64.0-68.4%. In contrast, inhibitors of potential nonoxidative antifungal mechanisms, iron salts to saturate iron chelators, and polyanionic amino acid polymers to neutralize cationic proteins did not block damage to hyphae by monocytes. Preparations rich in lysosomal granules from fractionated normal monocytes also did not damage hyphae. Overall, it appeared that oxidative mechanisms were most important for damage to hyphae by normal monocytes. Electron microscopy confirmed that Candida hyphae were damaged and probably killed by monocytes, but monocytes appeared to sustain significant damage in the process. In the absence of serum, monocyte cell membranes became closely approximated to Candida cell walls. It appeared that some Candida could escape this partial engulfment, as they were seen floating free with vesicular trilaminar membrane remnants covering hyphal surfaces. In general, monocytes appeared to be damaged by interactions with Candida hyphae more than neutrophils had been in previous studies. PMID- 6256410 TI - Simultaneous assay of immunoreactive beta-lipotropin, gamma-lipotropin, and beta endorphin in plasma of normal human subjects, patients with ACTH/lipotropin hypersecretory syndromes, and patients undergoing chronic hemodialysis. AB - We have studied the relative concentrations of the human immunoreactive (IR) peptides gamma-lipotropin (hgammaLPH, [1-58]hbetaLPH), beta-lipotropin (hbetaLPH), and beta-endorphin (hbetaEND, [61-91]hbetaLPH) using gel exclusion chromatography together with a specific radio-immunoassay (RIA) for hgammaLPH and a RIA that (because hbetaEND is the COOH-terminus of the hbetaLPH molecule) measures both hbetaEND and hbetaLPH on an equimolar basis. In normal subjects, basal plasma IR-hgammaLPH was often undetectable (<12.5 fmol/ml), but ranged up to 21 fmol/ml, and IR-hbetaEND/hbetaLPH was 10.8+/-0.7 fmol/ml; previous studies by others suggest that most of the IR-hbetaEND/hbetaLPH was probably hbetaLPH. Both IR-hgammaLPH and IR-hbetaEND/hbetaLPH were significantly elevated (P < 0.001) in patients undergoing chronic hemodialysis (101.5+/-12.7 and 23.8+/-2.0 fmol/ml, respectively). Their IR-hgammaLPH coeluted with standard hgammaLPH as a single peak, and IR-hbetaEND/hbetaLPH coeluted with hbetaLPH; no distinct peak of IR-hbetaEND was observed. In patients with ACTH/LPH hypersecretion due to Addison's disease, Nelson's syndrome, or ectopic ACTH syndrome, IR-hgammaLPH and IR-hbetaEND/hbetaLPH were both elevated, and IR-hbetaEND/hbetaLPH eluted as two peaks, one coeluting with hbetaLPH and the other with hbetaEND. The molar concentrations of all three peptides were significantly correlated with one another. The lower concentrations of endogenous IR-hbetaEND observed may be due in part to its apparent shorter plasma half-life, as estimated in an Addison's patient given a cortisol infusion. The biologic significance of these three peptides in circulating blood is still unknown. The increased levels of hbetaLPH and hgammaLPH in plasma of patients with chronic renal failure suggest that the kidney may be an important organ for their metabolism. PMID- 6256412 TI - Impaired angiotensin conversion and bradykinin clearance in experimental canine pulmonary emphysema. AB - Chronic hypoxic lung diseases are associated with abnormal blood pressure regulation. Because the lung is the principal site of angiotensin conversion and because hypoxia decreases converting enzyme activity, we examined whether angiotensin converting enzyme activity was impaired in lung disease. 12 dogs received a 6 wk course of aerosolized and intratracheal papain that produced moderate panlobular emphysema. These dogs and 24 control dogs were anesthetized and sampling catheters were placed under fluoroscopic control. Angiotensin conversion was measured by a blood pressure response bioassay. Pulmonary converting enzyme activity was also assessed by infusing bradykinin (BK) and using radioimmunoassay to measure the instantaneous clearance of BK and the concentration of BK in the pulmonary artery which first produced spillover of BK into left atrial blood. Angiotensin conversion was reduced in the emphysematous dogs to 81.1% (13.2 SD) from 92% (6 SD) in the control dogs (P < 0.01). Instantaneous clearance of BK in the emphysematous dogs was only slightly reduced (93%), despite reduction in their Pao(2) to 75 mm Hg, indicating that the greatest proportion of the perfused vascular bed was exposed to alveolar Po(2) of >90 mm Hg. However, the barrier to BK passage provided by the lung, and measured by the spillover level, was reduced (1/4) to (1/2) that observed in control animals. That the defect was promptly corrected by supplemental oxygen indicates that regional pulmonary vascular converting enzyme activity had been impaired by regional alveolar hypoxia, which permitted some peptide to pass through the lungs unmetabolized. Determination of peptide metabolism in the lungs may provide a useful measure of regional alveolar hypoxia and may lead to new ways of assessing lung injury. PMID- 6256414 TI - Various enzyme activities in muscle and other organs of dystrophic mice. AB - To elucidate the metabolic abnormality of musclar dystrophy, 27 kinds of enzyme activity in various organs of control and dystrophic mice were examined. The organs examined included muscle, bone, heart, testis, uterus, spleen, thymus, submaxillary gland, stomach, pancreas, liver, kidney, brain, and lung. The activities of 14 different aminopeptidases, 5 endopeptidases, 4 glycosidases, phosphatase, esterase, and ribonuclease were measured. Most of the enzyme activities were significantly elevated in muscles and bones of dystrophic mice. These organs were similar in their patterns of enzyme abnormality. Among the 14 kinds of aminopeptidase activity studied, the degree of increased activity was greater for the aminopeptidases (AP):Ala-AP, Leu-AP, Met-AP, Phe-AP, Trp-AP, Gly Pro-Leu-AP. In addition to aminopeptidases, there were significant increases in activities of chymotrypsinlike enzyme, cathepsin C, cathepsin D, several glycosidases and neutral ribonuclease in the muscles of dystrophic mice. Similarly increased enzyme activity was also observed in organs other than muscle and bone. Furthermore, protein content in most organs was higher in dystrophic mice than in those of control mice. These abnormalities were seen in both males and females. The present results suggest that there are extensive abnormalities in the protein metabolism in dystrophic mice. It seems therefore that the therapeutic approach to muscular dystrophy should be studies not only from the well-known abnormality of intramuscular endopeptidases, but from other aspects as well. PMID- 6256415 TI - Effects of inhibition of microtubule assembly on bone mineral release and enzyme release by human breast cancer cells. AB - When supernates from the established human breast cancer cell line MCF-7 were applied to fetal rat long bones that had been labeled with 45Ca and devitalized to remove endogenous bone cells, mineral was released from the bones. The release of bone mineral by MCF-7 supernates was associated with increased basal release of hydrolytic enzyme activity by the tumor cells. The basal release of lysosomal enzymes and collagenolytic activity by MCF-7 cells with approximately twice that of mouse 3T3 cells, which did not cause mineral release by the fetal rat bones. Release of hydrolytic enzymes and bone mineral-releasing activity was increased by colchicine and vinblastine, drugs that inhibit microtubule assembly, but not affected by lumicolchicine. Time-course experiments performed on MCF-7 cells with or without colchicine showed that release of cathepsin D and collagenolytic activity was associated more closely with release of bone mineral and degradation of bone matrix than was the release of N-acetylglucosaminidase. The release of previously incorporated [3H]proline from the bones exposed to MCF-7 cell cultures was more closely associated with release of collagenolytic activity by MCF-7 cells than with release of cathepsin D or N-acetylglucosaminidase. These data suggest that breast cancer-mediated bone resorption in vitro is positively correlated with release of hydrolytic enzymes by the tumor cells, and release of these enzymes is enhanced by disassembly of microtubules. PMID- 6256416 TI - Steroids, gold, hydroxychloroquine. PMID- 6256413 TI - Antigens and antibodies cross-reactive to the murine mammary tumor virus in human breast cyst fluids. AB - Human breast cyst fluids were shown to contain low concentrations of IgA (15-78 micrograms/ml) and IgG (33-145 micrograms/ml). The IgA:IgG ratios in individual breast cyst fluids ranged from 1:0.6 to 1:4. These levels are considerably higher than their ratio in serum (1:7). IgA from 33% of the 40 fluids examined, and IgG from 10% of the fluids, reacted with the murine mammary tumor virus (MuMTV). The reactivity was detected by an enzyme-linked immunosorbent assay that measures antibody binding to both the envelope glycoprotein and core protein of the virus. In a second series of experiments. IgA from 28% of 40 breast cyst fluids reacted only with MuMTV while IgA from 30% of the fluids was reactive with both MuMTV and the Rauscher murine leukemia virus. Antigen reactive with antiserum to the 28,000 dalton MuMTV core protein (p28), was also identified in a 165,000-g pellet fraction from breast cyst fluids. In individual fluids, the extent of IgA binding to MuMTV was positively correlated (P less than or equal to 0.01) with the binding of anti-p28 antibody to the pellet of the breast cyst fluid. Fractions with the buoyant density of retroviruses (1.16-1.18 g/ml) or their cores (1.21 1.25 g/ml) were isolated from breast cyst fluids. These fractions contained a DNA polymerase capable of utilizing the reverse transcriptase-specific template, dG12 18 x poly rCm. In addition, they reacted with antiserum to MuMTV p 28 but not with antiserum to the 30,000-dalton Rauscher murine leukemia virus core protein. PMID- 6256417 TI - Eccrine porocarcinoma. AB - Eccrine porocarcinoma is an extremely rare malignant skin tumor arising from the eccrine sweat duct unit (acrosyringium). It presents histologically with nests of clear tumor cells in the epidermis and superficial dermis. In addition such clear tumor cells lie isolated high up in the epidermis, closely resembling Paget cells. The various tumors, which may originate from the acrosyringium and the histologic differential diagnosis of eccrine porocarcinoma are discussed. PMID- 6256418 TI - Studies on the motility of smooth muscles of the teats in lactating cows. AB - Rhythmic motility of teats in lactating cows in vivo was studied by an improved plethysmographic technique. Oxytocin was infused intravenously and drugs were injected into the artery of the filled udder. The beta-adrenergic agent, isoprenaline, induced relaxation of the teats whereas the alpha-adrenergic agents phenylephrine and noradrenaline, elicited contraction. In one animal however, noradrenaline always exerted a biphasic effect. Pre-treatment with propranolol, a beta-adrenergic blocking agent, changed the biphasic effect into a purely activating response. Adrenaline, which exhibits both alpha and beta effects, induced relaxation, but after propranolol treatment relaxation was abolished and even converted into contraction of the teat. It seems clear that both alpha and beta adrenoceptors are present in longitudinal smooth muscles of the teats. Milk losses as intermittent spurts were observed in several cows. Spurts occurred synchronously with rhythmical teat motility in the filled udder during oxytocin infusion. The intensity of milk leakage was increased by isoprenaline and inhibited by noradrenaline, indicating the presence of alpha and beta receptors in teat sphincter muscles. Starting and stopping of milk spurts in correlation with rhythmical teat contractions were studied by audiovisual synchronization of video recording tape. The most common type of spurt began near the middle of the teat's relaxation phase and ended either just before or exactly at the beginning of the contraction phase. Interruption of the spurt is primarily due to closure of the streak canal. PMID- 6256419 TI - The use of buffers. PMID- 6256420 TI - Assessing the outcomes of a home nursing programme: previously hospitalized versus non-hospitalized patients. AB - This study utilizes four outcome measures to compare the success of a home nursing programme on a group of patients previously hospitalized and a non hospitalized group. The outcome measures are: mortality, stabilization, hospitalization and nursing home confinement at discharge from the programme. No significant differences were found between the groups, except for nursing home confinement which was higher for the non-hospitalized group. The relationships remained the same even when age and functional status were considered as alternative hypotheses. Implications of this study suggest that home nursing programmes are likely to be as successful with previously hospitalized, as they are with non-hospitalized, patients. Secondly, in evaluating the impact of home nursing programmes on patients, the potential stabilizing influence of the hospital must be taken into account before examining the programme in isolation. PMID- 6256421 TI - Extraction and isolation of soluble and insoluble fiber fractions from the pinto bean (Phaseolus vulgaris). PMID- 6256422 TI - Inhibitory effects of corticosteroids and histamine on human lymphocytes. AB - Both corticosteroids and histamine inhibit mitogen-induced lymphocyte proliferation. Their mechanisms of inhibition were studied in lymphocytes exposed to methylprednisolone (MP) both in vivo and in vitro. Either in vivo MP treatment or in vitro histamine incubation depressed lymphocyte responsiveness to mitogen stimulation. The combination of both treatments depressed the proliferative responses to a further degree, representing a shift of baseline proliferation by in vivo MP treatment. For in vitro MP studies, normal lymphocytes cultured with varying concentrations of MP were significantly less stimulated by phytohemagglutinin (PHA) and concanavalin A (Con A). Addition of histamine (1 x 10(-3) M) as well as MP in vitro led to a further inhibition of proliferative responses of these cells in an additive pattern in cultures of all MP concentrations. Normal lymphocytes incubated in vitro with histamine, but not with MP, resulted in a rapid rise in intracellular cyclic adenosine monophosphate (cAMP). These findings suggest that corticosteroid and histamine act independently through different mechanisms. PMID- 6256423 TI - Effect of theophylline on cortisol secretion. AB - Theophylline is thought to improve asthma by increasing intracellular cyclic adenosine 3'-5'-monophosphate (cAMP) levels. It has been demonstrated in experimental animals that elevation of intracellular cAMP in the adrenal cortex causes an increased secretion of cortisol. We studied whether therapeutic doses of theophylline given intravenously and orally to human subjects over 3 days would increase cortisol secretion. A single-blind, 6-day protocol was employed in five normal and five asthmatic volunteers. Adrenal function was monitored by 8 A.M. and 4 P.M. serum cortisol and adrenocorticotropic hormone (ACTH) levels; daily 24-hr urine for urinary-free cortisol (UFF), 17-hydroxysteroids (17-OH), and 17-ketosteroids (17-KS); and alternate-day cortisol secretory rates (FSR) measured by isotope dilution after intravenous 14C-cortisol. Serum theophylline concentration also was monitored. Results in normal and asthmatic subjects were similar. Theophylline caused a significant but transient increase in UFF and 17 OH excretion. Urine volumes also increased significantly, suggesting that the renal effect of theophylline accounted for the increased UFF and 17-OH excretion. FSR increased during the first 24 hr after theophylline in eight of nine cases (p < 0.05 by sign test), mean values increasing from 14.2 to 19.3 mg, but this effect had dissipated by day 3 of theophylline administration. In contrast to these findings, theophylline had no effect on serum cortisol or ACTH or urinary 17-KS. It is likely that serum cortisol and ACTH remained unchanged because the increase in cortisol secretion was offset by a concomitant increase in cortisol clearance. It is concluded that theophylline produces a small, transient increase in cortisol secretion and clearance, and this effect is similar in asthmatic and normal subjects. PMID- 6256424 TI - The granulocyte response to the phosphodiesterase inhibitor RO 20-1724 in asthma. AB - Isolated human granulocytes secrete the lysosomal enzyme beta glucuronidase when incubated with complement-activated zymosan particles. Isoproterenol inhibits this release, and the beta adrenergic response is associated with an increase in granulocyte cyclic adenosine monophosphate (cAMP) levels. In asthma, the beta adrenergic responsiveness is impaired. Cyclic AMP concentration in the granulocyte is also influenced by phosphodiesterase hydrolysis of this cyclic nucleotide. We found that the potent phosphodiesterase inhibitor, RO 20-1724, inhibited zymosan-stimulated beta glucuronidase release from granulocytes in a dose-dependent fashion (10(-8) to 10(-4) M). The inhibition of lysosomal enzyme release by RO 20-1724 was associated with an increase in granulocyte cAMP. Granulocytes were also isolated from asthmatic patients and the RO 20-1724 inhibition of beta glucuronidase release was compared with the response in normal subjects. The negative log molar median effective dose (ED50) value (mean +/- SE) was 5.98 +/- 0.69 in normal subjects and 5.90 +/- 0.63 in asthmatics. These observations suggest that the granulocyte metabolism modulated by the RO 20-1724 sensitive phosphodiesterase is equally responsive to this potent phosphodiesterase inhibitor in normal and asthmatic leukocytes. PMID- 6256425 TI - A case for medical coeducation in the 1870s. PMID- 6256427 TI - Women entering medical school: the challenge continues. PMID- 6256426 TI - Full time, part time, and flextime--all three can work for you. PMID- 6256428 TI - AMWA's experiment in planned change: a report on the "women in medical academia" project. PMID- 6256429 TI - Problems facing American medicine--a student viewpoint. PMID- 6256430 TI - Formulation and some biological uses of a buffer mixture whose buffering capacity is relatively independent of pH in the range pH 4-9. AB - A mixture is described which has a buffering capacity which is essentially independent of pH in the range pH 4.0-9.0. It is shown how this buffer mixture may be used to determine the force-flux relationship of proton transfer between two aqueous phases separated by a phospholipid bilayer in vesicular systems and so demonstrate that this relationship is linear over a wide range of delta mu approximately H+. The buffer mixture can, furthermore, be employed to determine the volume enclosed within a vesicular preparation. PMID- 6256431 TI - An airfuge centrifugation procedure for the measurement of ligand binding to membrane-associated and detergent-solubilized plasma membrane receptors. AB - A method is described in which high-speed centrifugation of membranes through an oil phase is used to separate membrane-bound and detergent-solubilized polypeptide receptor-iodinated ligand complexes from unbound ligands. Three centrifuges, the Brinkmann Eppendorf (5412), the Beckman Microfuge B and the Beckman Airfuge were evaluated for this capability. Under the conditions described, the Beckman Airfuge surpassed the others in recovering previously 125I and 32P-labelled cell membranes. The Airfuge method was compared with the more classically employed membrane filtration method to measure specific [125I]insulin and [125I]thrombin binding to human placental membranes and an enriched plasma membrane fraction from mouse embryo fibroblasts, respectively, are found to be 4 to 6 times more sensitive. For example, specific binding of ligand to its receptor was demonstrated with 5 micrograms of protein. With slight modifications, the polyethyleneglycol 6000 method of precipitating 125I-labelled ligand-soluble receptor complexes can be adapted to the Airfuge sedimentation through oil procedure. PMID- 6256432 TI - A tracking marker for the first dimension of the two-dimensional gel electrophoresis of ribosomal proteins. PMID- 6256433 TI - [Circumstances of discovery of "borderline" lesions of the breast]. PMID- 6256434 TI - The bacteriological quality of minced beef in the U.K. AB - Minced (ground) beef from three supermarkets, three intermediate-sized chain butchers and three small family butchers in each of three geographical areas was examined three times in warm weather and three times in cool. The total viable count (37 and 20 degrees C), numbers of Enterobacteriaceae (37 and 17 degrees C), and presumptive coliforms did not differ significantly between shop type or season. Statistically significant differences in numbers of faecal Streptococci, Staphylococcus aureus and Clostridium perfringens were too small to be of commercial importance, or diagnostic value. PMID- 6256436 TI - Cell-surface immunoglobulin and insulin receptor expression in an EBV-negative lymphoma cell line and its EBV-converted sublines. AB - Membrane Ig and insulin receptors were assayed in the EBV-negative Ramos lymphoma line and its EBV-converted sublines by surface fluorescence. 125I-protein A binding assay, immunoprecipitation, and insulin receptor assay. The original Ramos line expressed surface IgM but not IgD and had a low concentration of insulin receptors. Ten of 10 converted lines expressed IgD and a variable but usually high insulin-binding capacity. Molecular weight analysis of immunoprecipitated Ig showed the presence of 2 mu-chains and 2 delta-chains. One of each heavy chain type could be characterized as membrane Ig, whereas the other was cytoplasmic. Antisera against the lambda-chain precipitated mu and delta heavy chains as well, indicating that the delta-chain expressed on the membrane of the EBV-converted Ramos lines is bound to the lambda light chain. The results show that the differentiation of a Burkitt lymphoma line is not completely "frozen" and can be induced to change in a more "activated" direction by EBV conversion. PMID- 6256435 TI - A survey of virus infections of the respiratory tract of cattle and their association with disease. AB - A total of 1590 caves were investigated between May 1972 and December 1975. Twenty-two per cent were treated for respiratory disease and 2 . 5% died of pneumonia. Almost 80% of the respiratory illness occurred in six sharp outbreaks. Samples of virology were collected routinely from 127 healthy calves and from 354 calves treated for respiratory signs and comprised 1143 nasopharyngeal swabs and 1069 sera. Virus infections were detected on 540 occasions including 135 by parainfluenzavirus type 3 (Pi-3), 78 by respiratory syncytial virus (RSV), 103 by rhinovirus, 49 by bovine virus diarrhoea virus (BVDV), 29 by adenoviruses, 53 by reoviruses and 88 by enteroviruses. The seasonal and age distribution of infections differed between viruses. Only infections by RSV, Pi-3 and BVDV were significantly associated with disease. PMID- 6256437 TI - Regulation of human polymorphonuclear leukocyte superoxide release by cellular responses to chemotactic peptides. PMID- 6256439 TI - Defective Fc-mediated phagocytosis in C3H/HeJ macrophages. II. Correction by cAMP agonists. AB - Peritoneal macrophages from LPS hyporesponsive C3H/HeJ mice lose the capacity to bind and phagocytose opsonized sheep erythrocytes (EA) over a 48-hr culture period. This loss in Fc receptor capacity is markedly different from the progressive increase in phagocytic ability exhibited by cultured macrophages derived from LPS-responsive C3H/HeN mice. Since dibutyryl-cyclic adenosine monophosphate (DBcAMP) has previously been reported to modulate membrane receptor expression in lymphocytes and certain macrophage-like cell lines, we examined its effects on EA binding and phagocytosis by C3H/HeJ macrophages. DBcAMP not only reverses the binding defect in C3H/HeJ macrophages but also restores EA phagocytosis to the level of control C3H/HeN cultures. 8-Bromo-cAMP, as well as other agents known to elevate intracellular cAMP (i.e., isoproterenol plus isobutylmethylxanthine or prostaglandin E2) also corrected the phagocytic defect. Since the C3H/HeJ macrophage phagocytic defect can also be reversed by in vitro stimulation with a lymphokine-rich culture supernatant, we examined the effect of this treatment on intracellular cAMP levels. Lymphokine treatment produced a 60% increase in the levels of macrophage intracellular cAMP. These findings suggest that the C3H/HeJ differentiation defect may be secondary to some abnormality in a cAMP dependent pathway. PMID- 6256438 TI - The potential importance of soluble deoxynucleotidase activity in mediating deoxyadenosine toxicity in human lymphoblasts. AB - Deoxyadenosine and its nucleotides have been implicated in the pathogenesis of the immune dysfunction associated with a genetic deficiency of adenosine deaminase (ADA). We have previously shown that when ADA is blocked with a synthetic inhibitor, human T lymphoblastoid cell lines are more sensitive to deoxyadenosine toxicity, dephosphorylate deoxyadenosine nucleotides at a slower rate, and have much lower levels of ecto-5'-nucleotidase than most B cell lines. It seemed unlikely, however, that an enzyme on the outer surface of the lymphocyte plasma membrane could regulate intracellular deoxynucleotide catabolism. We now report that human lymphoblasts also contain a soluble deoxynucleotidase activity that is distinguishable from the plasma membrane enzyme by several criteria. In multiple human lymphoblastoid cell lines of varying origin and phenotype. soluble deoxynucleotidase correlated significantly (rs = 0.80, p < 0.001) with sensitivity to deoxyadenosine toxicity. PMID- 6256440 TI - Inability of mice to generate cytotoxic T lymphocytes to vesicular stomatitis virus restricted to H-2Kk or H-2Dk. AB - H-2k mice are unable to generate cytotoxic T lymphocytes (CTL) to vesicular stomatitis virus (VSV). This apparent unresponsiveness is found for both major serotypes of VSV, VSV-Indiana and VSV-New Jersey. CTL unresponsiveness occurs despite the ability of H-2k mice to generate a humoral immune response against VSV that is comparable to that found in responder (H-2b and H-2a) strains. All H 2k mice regardless of background genes, including various Ig allotypes, were found to be nonresponders. H-2k-linked unresponsiveness mapped to both H-2Kk and H-2Dk and occurred despite the presence of responder alleles in (responder x nonresponder)F1 mice. The unresponsiveness cannot be attributed to an inability of VSV-infected H-2k target cells to express viral surface antigens of H-2 molecules. Further, unresponsiveness cannot be overcome by using secondary stimulation in vivo or in vitro. H-2k-linked unresponsiveness does not appear to be due to suppression, and no complementation has been found in various (nonresponder x nonresponder)F1 mice. Thus unresponsiveness to VSV in association with H-2Kk or H-2Dk appears to represent an extensive defect of immune responsiveness that probably occurs because VSV is not a natural mouse pathogen. PMID- 6256441 TI - Peroxidase-mediated toxicity to schistosomula of Schistosoma mansoni. AB - Guinea pig eosinophil peroxidase (EPO) was capable of killing schistosomula of Schistosoma mansoni in vitro when combined with hydrogen peroxide and a halide. Killing was measured by 51Cr release, by microscopic evaluation of viability, and by reinfection experiments in mice. Parasite killing was dependent on each component of the EPO-H2O2-halide system, was completely inhibited by catalase and azide, and was partially inhibited by cyanide. The EPO-mediated system required 10(-4) M H2O2 and 10(-4) M iodide at pH 7.0, and the schistosomula were killed with exposure to this system of less than 30 min at 37 degrees C. At pH 6.0, the EPO-mediated system showed significant cidal activity with 10(-6) M iodide. Canine neutrophil peroxidase (myeloperoxidase [MPO]) was also able to kill schistosomula in vitro in the presence of 10(-4) M H2O2 and 10(-4) iodide at pH 7.0 and pH 6.0. Physiologic concentrations of chloride (0.1 M) could substitute for iodide at pH 7.0 and pH 6.0 as the halide cofactor; however, at pH 7.0, a higher concentration of enzyme was required. These findings with isolated enzyme systems are compatible with a role for peroxidase in the host defense against schistosomula. PMID- 6256442 TI - Human B cell activation in vitro: augmentation and suppression by monocytes of the immunoglobulin production induced by various B cell stimulants. PMID- 6256443 TI - The effects of macrophage depletion on the clinical and pathologic expression of experimental allergic encephalomyelitis. PMID- 6256445 TI - Mitogen-induced blast cells of C type virus-infected mice as target cells for cytolytic T lymphocytes. AB - Lymphoma cells induced in vivo by exogenous C type viruses are usually used as target cells to test the activity of cytolytic T lymphocytes (CTL) directed against the virus-induced cell surface FMR antigen. Such lymphomas are available only in a small number of inbred strains of mice, thus setting limits to the study of H-2 antigens in the interaction between CTL and tumor target cells. A method is proposed to overcome this, using mitogen-induced blast cells from adult mice neonatally infected with C type viruses. Such blast cells bear serologically detectable viral antigens and function as convenient targets in the chromium release test, as well as competitor cells or stimulator cells in vitro. With this method it has been possible to study T cell-mediated anti-FMR reactions in 12 different inbred strains of mice bearing 10 different H-2 haplotypes. The same method could probably be used in any inbred strain, greatly improving the possibility of immunogenetic studies in C type virus systems. PMID- 6256444 TI - Modulation of Fc-receptor expression and Fc-mediated phagocytosis in variants of a macrophage-like cell line. PMID- 6256446 TI - Selection of antibodies for the immunofluorescent localisation of cyclic GMP in the central nervous system. AB - Radioimmunoassay techniques have been used to determine why only a small number of antibodies against cyclic GMP are able to show immunofluorescent staining in the central nervous system. However, neither the titre, avidity nor specificity as determined in liquid-phase radioimmunoassay employing [3H]cyclic GMP, have been able to predict whether a given antibody will show specific staining, or account for the different sites of immunofluorescent localisation observed with these antibodies. These observations are discussed in terms of the populations of antibody molecules employed in the radioimmunoassay and immunofluorescent procedures. PMID- 6256447 TI - A simple method for the purification of 5-aminosalicylic acid. Application of the product as substrate in enzyme-linked immunosorbent assay (ELISA). AB - Commercially available 5-aminosalicylic acid (5-AS) was recrystallised in the presence of Na2S2O5. A completely colourless solution was obtained when the purified product was dissolved at a concentration of 1 mg/ml in a phosphate buffer containing EDTA and H2O2. No significant increase in absorption was found upon storage for 18 h at 4 degrees C. A 8-fold increase in sensitivity of an enzyme-linked immunosorbent assay for the detection of rotavirus antigens was demonstrated by using the modified substrate solution instead of the conventional substrate solution of crude 5-AS. In addition, P/N values did not significantly change between 2 and 18 h after addition of the substrate, thus rendering the time of reading less critical. No difference in sensitivity of the assay was found between modified 5-AS solution and ortho-phenylenediamine (OPD). However, since OPD requires special care in handling the modified 5-AS solution is preferred for use in routine ELISAs. PMID- 6256448 TI - The applicability of freeze-thaw Percoll gradients to whole-cell isopycnic fractionations: preliminary results. AB - The freeze-thaw method of gradient generation, using Percoll as the density medium, is shown to be adaptable for the isopycnic sedimentation of live whole cells. Methods of controlling gradient profiles are examined with preliminary evidence showing that three types of cells brought to isopycnic equilibrium in these gradients and recovered from them retain satisfactory levels of several vital functions. PMID- 6256449 TI - Efficient separation of human T lymphocytes from venous blood using PVP-coated colloidal silica particles (percoll). AB - In a comparative study, human peripheral T lymphocytes were separated as E rosettes by density centrifugation through various gradient media. Sheep red blood cells (SRBC) were removed by dissociation of the E rosettes at 37 degrees C with subsequent centrifugation on a similar density gradient prewarmed to 37 degrees C. In particular, gradients made of Ficoll Urovison were compared with Percoll gradients with regard to both separation steps. Using Percoll gradients, a maximal T cell recovery of 75% was obtained, whereas Ficoll separation yielded only 46%. T lymphocytes separated with Percoll exhibited equal viability compared to Ficoll isolated cells and consisted of 98% EAET-RFC. No inhibition of cellular function by Percoll treatment was detected, whereas Ficoll treatment led to an impaired mitogenic response. An inherent mitogenicity of Percoll was not observed. The method described results in considerably shortened centrifugation times due to the low viscosity of the Percoll medium and simultaneously seems to be less harmful to the rather fragile rosettes. Reproducibility was found to depend on careful control of density and osmolarity of the Percoll medium. PMID- 6256450 TI - Determination of immunoglobulin classes of specific antibodies secreted by single cells. A cluster formation assay. AB - A method is described to identify specific antibody-forming cells and their immunoglobulin classes by a multilayer cluster formation. Cells producing specific antibodies are mixed with erythrocytes coated with the corresponding antigen in presence of rabbit anti-human immunoglobulins. Clusters are formed only if the mixtures contain rabbit antiserum against the immunoglobulin chains of the specific secreted antibody. Thus the immunoglobulin class of the specific antibody is assessed. For this study the cells of three EBV-transformed, antibody producing human lymphoblastoid cell lines were used. PMID- 6256451 TI - The regulation of complement activity by pharmacologic agents. PMID- 6256452 TI - Effect of prostaglandin E1 on the level of cAMP in bone marrow macrophages. Inhibition of phagocytosis and cell shape changes. AB - The effect of prostaglandins E1 (PGE1) and F2 alpha (PGF 2 alpha) on levels of cAMP, cell shape and phagocytosis of zymosan were examined. The addition of 10( 6) M PGE1 induced an immediate rise in the level of cAMP which fell again after 2.5 min. Phagocytosis was inhibited only after 60 min. of drug treatment. PGF 2 alpha did not show this effect. Neither db-cAMP or papaverine showed a similar effect on phagocytosis and cell shape to that produced by PGE1 treatment. Therefore, we conclude, that PGE1 does at least not exclusively act by changing cAMP levels, but rather directly influences cell membrane functions. PMID- 6256453 TI - Enhanced macrophage and natural killer cell antitumor activity by various molecular weight maleic anhydride divinyl ethers. AB - A series of Maleic anhydride divinyl ether (MVE) polyanions, synthesized with molecular weight ranging from 12500 to 52600, were found capable of enhancing macrophage tumoricidal activity of MBL-2 leukemia cells. These agents also augmented Natural Killer cell activity against the YAC lymphoma and M109 adenocarcinoma cell lines. PMID- 6256454 TI - Induction of differentiation of human null cells into T lymphocytes under the influence of serum of mice treated with sodium diethyldithiocarbamate. AB - Mouse serum collected 24 hr after administration of sodium diethyldithiocarbamate was shown to convert a subset of null cells, not bearing the human T lymphocyte differentiating antigen (HTLA cells) into HTLA+ cells in man. In addition to inducing surface characteristics of T lymphocytes, the serum of treated mice increased functional activities of human peripheral blood lymphocytes, including the response to Con A and the suppressor activity in vitro. PMID- 6256455 TI - [A successful emergency operation on extensive primary tracheal tumor (author's transl)]. PMID- 6256456 TI - Cystosarcoma phyllodes. PMID- 6256457 TI - Marijuana for nausea and vomiting in cancer patients. PMID- 6256458 TI - Inhibition of secretion of luteinizing hormone induced by electrochemical stimulation of the anterior cingulate cortex mediated by a beta-adrenergic mechanism. AB - Release of LH occurred in ovariectomized, oestrogen-primed rats when the medial preoptic area (mPOA) was electrically stimulated with monophasic square pulses of 1 ms duration (50 Hz, 150 microA, 15 s on and 15 s off for 30 min). Electrochemical stimulation of the anterior cingulate area applied immediately after the first 15 min period of stimulation in the mPOA completely prevented the rise in LH normally observed during the following 15 min. This effect was suppressed either by selective blockade of noradrenaline synthesis with diethyldithiocarbamate, or following systemic or intraventricular injection of the beta-adrenergic blocker, propranolol, whereas it did not change after systemic atropine, pimozide or phenoxybenzamine. Isoprenaline, a beta-adrenergic agonist, injected into the third ventricle of rats stimulated in the mPOA mimicked the effect of the cortical stimulation, this effect was also blocked by propranolol. Intraventricular administration of propranolol or of isoprenaline had no effect on the release of LH induced by the injection of gonadotrophin releasing hormone, showing that their action is not directly on the pituitary gland. Intraventricular injection of noradrenaline, which failed to affect the release of LH induced by stimulation in the mPOA, inhibited this release when animals were pretreated with phenoxybenzamine. On the other hand, the LH releasing potency of noradrenaline was greatly increased if the beta-receptors were blocked. From these results it may be concluded (1) that inhibition of the secretion of LH evoked by electrochemical stimulation of the anterior cingulate cortex is mediated by an adrenergic mechanism involving a beta-receptor and (2) that noradrenaline exerts an inhibitory effect on the secretion of LH through a beta-receptor in addition to the known facilitatory action through an alpha receptor. PMID- 6256459 TI - Cholinergic motor control of sea urchin tube feet: evidence for chemical transmission without synapses. AB - Isolated tube feet of Strongylocentrotus franciscanus contract briefly when the outer epithelium is touched. Similar twitch-like contractions can be induced by electrical stimulation of the outer surface of the tube foot. These responses appear to be chemically mediated. The following evidence indicates that the transmitter substance may be acetylcholine (ACh): ACh causes muscle contraction. This effect and that of electrical stimuli is potentiated by anticholinesterase agents and is antagonized by cholinergic blocking agents. Anaesthesia with chloralhydrate or chloretone abolishes responsiveness to mechanical or electrical stimulation but not to ACh. Desensitization with carbachol prevents responses to ACh and to mechanical or electrical stimulation. There are no neuromuscular synapses and no axons can be detected which cross the connective tissue layer which separates the muscle fibres from the subepithelial nerve plexus. The latter is known to contain conspicuous amounts of ACh; nerve terminals containing clear vesicles invest the outer surface of the connective tissue layer. All evidence indicates that chemical transmission involves diffusion of ACh (released from activated nerve terminals) across this connective tissue layer which is around 5 micron thick in fully extended tube feet but may have a thickness of 20 or even 25 micron in less extended ones. Calculations based on equations describing transmitter diffusion prove the feasibility of such a mechanism. PMID- 6256460 TI - Divalent cations as charge carriers during two functionally different membrane currents in the ciliate Stylonychia. AB - We have investigated the ability of various divalent cations to carry current through membrane channels in ciliates activated by mechanical stimulation and by membrane depolarization. Both types of channels are identified as Ca2+ channels. Whereas Ba2+ ions and Sr2+ ions can replace Ca2+ ions as charge carriers during either kind of current, Mg2+ ions can carry the current evoked by mechanical stimulation but not the current elicited by membrane depolarization. Mn2+ ions did not carry either of these currents, and they reduced the currents carried by Ca2+ ions. Our experiments suggest that the mechano-sensitive and the voltage sensitive channels exhibit different selectivities for divalent cations. PMID- 6256461 TI - In vitro generation of cytotoxic lymphocytes against radiation- and radiation leukemia virus-induced tumors. III. Suppression of anti-tumor immunity in vitro by lymphocytes of mice undergoing radiation leukemia virus-induced leukemogenesis. AB - Adult C57BL/6 mice exposed to fractionated irradiation or inoculated with the radiation leukemia virus (RadLV), develop high incidence (80-100%) of lymphatic leukemias within 3-6 mo. RadLV-induced lymphomas can elicit cytotoxic responses in vitro in lymphocytes of preimmunized syngeneic mice, a reaction that is dependent on the expression of membrane-associated viral antigenicity. As soon as 5 d after RadLV inoculation, and during the entire leukemogenic process, suppressor T cells are detectable in the spleen that are capable of specifically abrogating generation of syngeneic anti-tumor cytotoxic cells in vitro. Mice exposed to fractionated x irradiation do not develop suppressor cells and their splenocytes may be stimulated in vitro to generate cytotoxicity toward RadLV induced leukemias. These findings suggest that although RadLV has been isolated from radiation-induced leukemias, x-ray- and RadLV-induced leukemogenesis do not seem to involve a common viral etiology, and that induction of suppressor cells during RadLV leukemogenesis may be essential for tumor progression. PMID- 6256462 TI - Pre-B cells and other possible precursor lymphoid cell lines derived from patients with X-linked agammaglobulinemia. AB - A group of unique Epstein-Barr virus-containing cell lines was derived from the bone marrow of three patients with X-linked agammaglobulinemia. Efforts to obtain cell lines from the peripheral blood of these patients were uniformly unsuccessful. Immunofluorescence analyses as well as biosynthetic studies with [(35)S]methionine indicated unusual patterns of Ig synthesis in many of these bone marrow derived lines. Seven of the lines were of particular interest in that two produced no Ig of any type; two others showed no Ig by fluorescence but small amounts by [(35)S]methionine labeling; one expressed only cytoplasmic mu chains without any evidence of light chain synthesis, and two produced primarily mu chains with only slight amounts of light chains. One of the lines without membrane or cytoplasmic Ig studied in detail grew like a typical lymphoid line and was carried in intermittent culture over a period of 2 yr without Ig expression. One line grew quite differently and resembled the round cell type described previously, which has been obtained from a variety of sources. The cell line with cytoplasmic mu chains and no light-chain expression had the characteristic properties of pre-B cells. Three normal type Ig-producing cell lines also were obtained from the patients. The accumulated evidence obtained in the present study indicates that these unusual cell lines represent normal precursor cells of the B-cell lineage; these grew out in these cases because of the virtual absence of mature B cells that ordinarily overgrow the culture system. However, the possibility that in certain instances they reflect abnormal Ig synthesis characteristic of the disease has not been ruled out. PMID- 6256463 TI - Macrophage oxygen-dependent antimicrobial activity. III. Enhanced oxidative metabolism as an expression of macrophage activation. AB - The capacity of 15 separate populations of mouse peritoneal macrophages to generate and release H2O2 (an index of oxidative metabolism) was compared with their ability to inhibit the intracellular replication of virulent Toxoplasma gondii. Resident macrophages and those elicited by inflammatory agents readily supported toxoplasma multiplication and released 4-20X less H2O2 than macrophages activated in vivo by systemic infection with Bacille Calmette-Guerin or T. gondii, or by immunization with Corynebacterium parvum. Immunologically activated cells consistently displayed both enhanced H2O2 production and antitoxoplasma activity. Exposure to lymphokines generated from cultures of spleen cells from T. gondii immune mice and toxoplasma antigen preserved both the antitoxoplasma activity and the heightened H2O2 release of toxoplasma immune and immune-boosted macrophages, which otherwise were lost after 48-72 h of cultivation. In vitro activation of resident and chemically-elicited cells by 72 h of exposure to mitogen- and antigen-prepared lymphokines, conditions that induce trypanocidal (5) and leishmanicidal activity (14), stimulated O2- and H2O2 release, and enhanced nitroblue tetrazolium reduction in response to toxoplasma ingestion. Such treatment, however, failed to confer any antitoxoplasma activity, indicating that intracellular pathogens may vary in their susceptibility to macrophage microbicidal mechanisms, including specific oxygen intermediates. In contrast, cocultivating normal macrophages with lymphokine plus heart infusion broth for 18H rendered these cells toxoplasmastatic. This in vitro-acquired activity was inhibited by scavengers of O2-, H2O2, OH., and 1O2, demonstrating a role for oxidative metabolites in lymphokine-induced enhancement of macrophage antimicrobial activity. These findings indicate that augmented oxidative metabolism is an consistent marker of macrophage activation, and that oxygen intermediates participate in the resistance of both in vivo- and vitro-activated macrophages toward the intracellular parasite, T. gondii. PMID- 6256464 TI - Activation of macrophages for enhanced release of superoxide anion and greater killing of Candida albicans by injection of muramyl dipeptide. AB - The adjuvant muramyl dipeptide (MDP) has been shown to affect a number of macrophage functions in vitro. We studied the effect of subcutaneous injection of MDP into mice. Cultured peritoneal macrophages from treated mice displayed increased spreading, total cell protein, and specific activity of beta glucosaminidase a constituent of macrophage lysosomes, and of lactate dehydrogenase. Generation of superoxide anion (O2-) by MDP-treated macrophages stimulated by contact with phorbol myristate acetate was enhanced by over fivefold to levels achieved by macrophages from bacillus Calmette-Guerin-infected mice. The enhancement in stimulated O2- release was noted by 1 h after injection of MDP, peaked by 3 h, and remained high for at least 48 h. Priming for enhancement of O2- release by MDP was similar in athymic nude mice and in normal littermates, suggesting that mature T lymphocytes are not involved in this MDP effect. Priming for enhanced stimulated O2- release, and morphologic and enzymic changes, were not achieved by injection of the D-D stereoisomer of MDP. Phagocytosis of Candida albicans was only slightly greater by macrophages from mice give MDP, but MDP-stimulated cells killed two times more C. albicans in vitro than did cells from untreated animals. When MDP was given 18 h before, simultaneously with, or 24 h after lethal infectious challenge with C. albicans, treated mice were protected compared with controls. These results suggest that injection of MDP effectively and rapidly activates macrophages in the recipient animal. This agent should serve as an important probe of macrophage physiology and, perhaps ultimately, as a means of enhancing host defense in humans. PMID- 6256466 TI - Sendai virus-specific, H-2-restricted cytotoxic T lymphocyte responses of nude mice grafted with allogeneic or semi-allogeneic thymus glands. AB - The in vitro secondary cytotoxic T lymphocyte (CTL) response to Sendai virus treated stimulator cells by primed spleen cells from thymus gland-grafted nude mice was examined. BALB/c (H-2d) nude mice grafted with allogeneic C57BL/10 (H 2b) thymus glands developed CTL responses directed exclusively to Sendai virus infected H-2d target cells. (C57BL/6 X BALB/c)F1 nude mice grafted with thymus glands of either parent developed CTL responses preferentially against infected target cells expressing the MHC antigens present in the parental thymus graft, but also had detectable activity for infected target cells of the parental haplotype not expressed in the thymus. These results provide evidence against the concept that self recognition by MHC-restricted CTL is directed exclusively by the MCH type of the thymus. PMID- 6256465 TI - Identification of tryptic peptides unique to a 110,000-molecular weight polyprotein encoded by the T-8 isolate of murine leukemia virus. AB - Mink cells nonproductively-infected with the weakly-transforming T-8 isolate of murine leukemia virus (MuLV) express a 110,000 mol wt polyprotein designated T-8 P110. By immunoprecipitation analysis, T-8 P110 is shown to contain AKR-MuLV amino terminal gag gene-specific components (p15, p12) but to lack p30, p10, gp70, and p15(E) antigenic determinants. These observations are further substantiated by tryptic peptide analysis indicating T-8 P110 to share approximately six lysine-containing tryptic peptides with AKR-MuLV Pr65gag, and none with AKr-MuLV Pr82env. Furthermore, of seven methionine-containing T-8 P110 tryptic peptides, at least four can be conclusively shown not to be present in either AKr-MuLV Pr180gag/pol or Pr82env. A clonal mink cell line nonproductively infected by T-8, and expressing high levels of P110, although not morphologically transformed, is shown to lack elevated levels of tyrosine-specific protein kinase activity and reduction of epidermal growth factor binding sites characteristic of cells transformed by many other RNA-transforming viruses. These findings argue either that the T-8 viral genome contains acquired cellular sequences encoding a portion of P110, or that T-8 P110 represents an inphase deletion of AKR-MuLV Pr180gag/pol with extensive posttranlational modification and that an as yet unidentified protein is responsible for T-8 associated transformation. PMID- 6256467 TI - Receptors for cold-insoluble globulin (plasma fibronectin) on human monocytes. AB - This investigation focused on the role played by cold-insoluble globulin (CIg, plasma fibronectin) in monocyte function. Surface-bound CIg mediated a concentration-dependent of human blood monocytes to gelatin-coated surfaces. CIg also mediated the binding of gelatin-coated particles such as latex beads or tanned erythrocytes to surface-bound human monocytes. However, CIg did not mediate particle ingestion. Subfractionated CIg that was highly enriched in monomeric forms (zone II CIg, mol wt 190,000-235,000) was less effective than were fractions enriched in dimeric forms (zone I CIg, mol wt 450,000) in promoting monocyte attachment. Binding of CIg to a gelatin or plastic surface occurred in the absence of divalent cations, but monocyte attachment to CIg coated surfaces required divalent cations, Mg++ being much more effective than Ca++. Cation-dependent cell attachment was reversible in that bound cells could be released by treatment with EDTA. Serum-mediated binding of monocytes to gelatin-coated plastic dishes was a result of its content of CIg because the binding activity was abolished by removal of CIg from serum, and could be restored by readdition of purified CIg. Treatment of monocytes with trypsin abolished subsequent cell attachment to CIg-gelatin surfaces or particles. Expression of certain other known monocyte membrane receptors (Fc and C3b) was markedly enhanced as a result of CIg-monocyte interaction. These several observations indicate that monocytes bear membrane receptors (termed receptor cold-insoluble globulin) for surface-bound CIg. PMID- 6256468 TI - Studies on a new lymphocyte mitogen from Bordetella pertussis. I. Induction of proliferation and polyclonal antibody formation. AB - Pertussis B mitogen (PBM), isolated from culture supernatant fluids of Bordetella pertussis, is a potent mitogen for mouse and human lymphocytes. In mice, > 95% of the blast cells recovered from PBM cultures bear surface immunoglobulins. Therefore, PBM seems to induce proliferation of mouse B lymphocytes, but not T cells. The proliferative response observed is nonspecific because cells from all mouse strains tested, including germfree animals, are responsive. Moreover, the mitogenic activity of PBM is independent of T lymphocytes, macrophages, or serum factors. When human peripheral blood or cord blood lymphocytes are cultured in the presence of PBM, a high level of thymidine incorporation by these cells is detected. Furthermore, PBM can induce polyclonal antibody formation by both mouse and human lymphocytes. Despite similar methods of isolation, PBM is distinct from the lymphocytosis-promoting factor of B. pertussis, a previously described T cell mitogen. PMID- 6256469 TI - [Cylindrical epitheliomas of the ethmoid and wood-work]. PMID- 6256470 TI - Lack of effect of cannabinoids on carbonic anhydrase. AB - Cannabinoids have significant anticonvulsant effects, the mechanism of which is obscure. In addition, these agents reduce intraocular pressure. Inhibitors of carbonic anhydrase also share these two pharmacological actions. In order to investigate whether these actions of cannabinoids are mediated through inhibition of carbonic anhydrase (CA), commercial solutions of the enzyme were exposed to delta 9-tetrahydrocannabinol and cannabidiol. No inhibition was observed at concentrations of 10(-7)--10(-5) M. PMID- 6256471 TI - Protein and glycoprotein composition of myelin subfractions from the developing rat optic nerve and tract. PMID- 6256472 TI - Temperature coefficients for the oxidative metabolic responses to electrical stimulation in cerebral cortex. AB - Temperature coefficients of both cat and toad brain have been calculated for the active metabolic state induced by electrical stimulation. Values are higher than most of the values previously reported for "rest" metabolism, whether calculated from Arrhenius plots or from linear graphs. Relative rates of oxidative metabolism were obtained by measuring the time course of the transient changes in NADH fluorescence and cytochrome aa3 absorption by reflectance techniques directly from the surface of the exposed cat cerebral cortex in vivo and from the isolated intact toad brain mounted in a cuvet. These findings demonstrate that such optical methods accurately record metabolic processes. PMID- 6256473 TI - Ascorbate decreases ligand binding to neurotransmitter receptors. PMID- 6256474 TI - Calcium-dependent desensitization of adenylate cyclase in rat cerebral cortical slices. AB - Incubation of slices of rat cerebral cortical grey matter in Krebs-Ringer bicarbonate-glucose buffer induced a rapid decline in the responsiveness of the adenylate cyclase in subsequently prepared membrane preparations to stimulation by various activators of the enzyme. The loss of responsiveness was time- and temperature-dependent, showed an absolute dependence on extracellular calcium ions, and was mimicked by the presence of serine proteases in the incubation medium. The resultant adenylate cyclase preparation was partially responsive to activation by fluoride and guanylylimidodiphosphate but had become virtually unresponsive to activation by ganglioside, trypsin, or beta-adrenergic agonists. The loss of responsiveness of adenylate cyclase was not altered if slices were incubated with depolarizing agents, putative neurotransmitters, receptor blockers, serine protease inhibitors, or adenosine deaminase. The nature of the calcium-dependent mechanism involved in the loss responsiveness of membranal adenylate cyclase is unknown. A suggested mechanism for the loss of sensitivity is the action of a membrane-bound, calcium-dependent protease. PMID- 6256475 TI - Effects of detergents, proteins, and lipids on 2':3'-cyclic-nucleotide 3' phosphodiesterase activity. AB - The myelin marker 2':3'-cyclic-nucleotide 34'-phosphodiesterase (CNPase) was isolated to a lipid- and phosphate-free stage. The effects of exogenously added lipids were tested on this preparation and compared to the known stimulation of the enzyme by detergents and proteins. CNPase could be stimulated 2-3 fold by these various agents which appeared to be additive in their effect. Enzyme protein and enzyme-lipid interactions and possible medical use of the improved assay conditions for CNPase employed in the study are discussed. PMID- 6256476 TI - Characterization of [3H]guanine nucleotide binding sites in brain membranes. AB - [3H]GTP [guanosine triphosphate] and [3H]GMP-PNP [guanosine 5'-(beta, 8 imino)triphosphate, a nonmetabolized analog of GTP] have been utilized as ligands to characterize binding sites of guanine nucleotides to rat brain membranes. Binding of both [3H]GTP and [3H]GMP-PNP is saturable, with respective KD values of 0.76 and 0.42 microM. The number of binding sites for GMP-PNP (4 nmol/g) is three times greater than for GTP (1.5 nmol/g). This discrepancy is caused by rapid degradation of GTP to guanosine by brain membranes, which can be partially prevented by addition of 100 microM-ATP. The binding of [3H]guanine nucleotides is selective, with approximately equipotent inhibition by GTP, GDP, and GMP-PNP (at 0.2--1.0 microM), but no inhibition by other nucleotides at 100 microM concentrations. The bindings sites for guanine nucleotides in brain membranes appear not to be associated with microtubules, since treatments that reduce [3H]colchicine binding by 65% have no effect on [3H]GTP binding. [3H]Guanine nucleotide binding is widely distributed in various organs, with highest levels in liver and brain and lowest levels in skeletal muscle. The characteristics of these binding sites in brain show specificity properties of sites that regulate neurotransmitter receptors and adenylate cyclase. PMID- 6256477 TI - Cyclic AMP-dependent protein kinase activity in human brain across age. AB - Cyclic AMP-dependent protein kinase activity was measured in the cerebral cortex of humans 2 days to 83 years of age and in the cortex of F344 rats 3, 22, or 30 months of age. Protein kinase activity was detected in the human brain, but no age-related differences in activity were observed in the presence or absence of cyclic AMP. Age differences were also not seen in protein kinase in the rat cerebral cortex. Enzyme activities in rat and human brain were similar. PMID- 6256478 TI - Alterations in beta 1- and beta 2-adrenergic receptor density in the cerebellum of aging rats. AB - The densities of beta 1 and beta 2-adrenergic receptors were determined in homogenates of cerebral cortex and cerebellum of rats between 3 and 14 mo of age. No change in either receptor population occurred in the cortex during this period. In the cerebellum, a 20--25% decrease in the density of beta 2 receptors and a 350% increase in the density of beta 1 receptors occurred. The increase in beta 1 receptors in the cerebellum may be the result of a decrease in the function of the noradrenergic projections from the locus coeruleus which synapse on cerebellar Purkinje cells. PMID- 6256479 TI - Phosphorylation of endogenous proteins by adenosine 3':5'-monophosphate-dependent protein kinase in mouse neuroblastoma cells. AB - Increased intracellular adenosine 3':5'-monophosphate (cAMP) levels and activation of cAMP-dependent protein kinases (ATP:protein phosphotransferase, EC 2.7.1.37) in vivo were correlated in mouse neuroblastoma cells grown in the presence of 1 mM-6N,O2'-dibutyryl 3':5'-monophosphate (Bt2cAMP). The time course for activation showed that cAMP-dependent protein kinases were activated by 30 min. A heat-stable inhibitor protein inhibited a majority of activated cAMP dependent protein kinase. Activation of cAMP-dependent protein kinase caused additional phosphorylation of proteins when compared with untreated control cells, as demonstrated by endogenous phosphorylation of proteins in vitro using [gamma-32P]ATP and analysis by two-dimensional polyacrylamide gel electrophoresis. The phosphorylation data show selective phosphorylation of specific proteins by cAMP-independent and cAMP-dependent protein kinase. Among the proteins in the postmitochondrial supernatant fraction phosphorylated by cAMP dependent protein kinases, two proteins with a molecular weight of 43,000 were heavily phosphorylated. It is suggested that phosphorylation of cellular proteins by cAMP-dependent protein kinases might be involved in the cAMP-modulated biochemical changes in neuroblastoma cells. PMID- 6256480 TI - Multiple neurotransmitter receptors. PMID- 6256481 TI - Accumulations of cyclic AMP in adenine-labeled cell-free preparations from guinea pig cerebral cortex: role of alpha-adrenergic and H1-histaminergic receptors. AB - Norepinephrine, histamine, adenosine, glutamate, and depolarizing agents elicit accumulations of radioactive cyclic AMP from adenine-labeled nucleotides in particulate fractions from Krebs-Ringer homogenates of guinea pig cerebral cortex. The particulate fractions contain sac-like entities, which apparently are associated with a significant portion of the membranal adenylate cyclase. Particulate fractions from sucrose homogenates are a less effective source of such responsive entities. Activation of the adenine-labeled cyclic AMP-generating systems by norepinephrine is by means of alpha-adrenergic receptors, while activation by histamine is through H1- and H2-histaminergic receptors. Adenosine responses are potentiated by the amines and are antagonized by alkylxanthines. Glutamate and depolarizing agents appear to elicit accumulations of cyclic AMP via "release" of endogenous adenosine. It is proposed, based on the virtual absence of an alpha-adrenergic or H1-histaminergic response in the presence of a combination of potent adenosine and H2-histaminergic antagonists, that alpha adrenergic and H1-histaminergic receptor mechanisms do not activate adenylate cyclase directly in brain slices or Krebs-Ringer particulate fractions, but merely facilitate activation by beta-adrenergic, H2-histaminergic, or adenosine receptors. PMID- 6256482 TI - Cyclic AMP-generating systems in cell-free preparations from guinea pig cerebral cortex: loss of adenosine and amine responsiveness due to low levels of endogenous adenosine. AB - The accumulations of radioactive cyclic AMP elicited by adenosine, norepinephrine, and histamine in adenine-labeled vesicular entities of a particulate fraction from guinea pig cerebral cortex are greatly reduced as a result of prolonged preincubation. The presence of adenosine deaminase during preincubations largely prevents the loss of adenosine, norepinephrine and histamine responses. Adenosine deaminase was inactivated by deoxycoformycin prior to stimulation of cyclic AMP accumulation by adenosine or amines. If adenosine deaminase is not inactivated, responses to norepinephrine are not significant and histamine responses are reduced by 50%. Adenosine deaminase cannot restore responsiveness of the cyclic AMP-generating systems. It is proposed that, in particulate fractions of guinea pig cerebral cortex, low levels of adenosine cause a slow loss of receptors and/or coupling of receptors to cyclic AMP generating systems. PMID- 6256483 TI - Increase in striatal [3H]muscimol binding following intrastriatal injection of kainic acid: a denervation supersensitivity phenomenon. AB - The effect of intrastriatal microinjection of kainic acid (KA) on specific binding of [3h]muscimol to the particulate fractions obtained from corpus striatum (CS), globus pallidus (GP), substantia nigra (SN), and cerebral cortex (CC) was examined. Seven days after the unilateral intrastriatal microinjection of KA, the amount of specifically bound [3H]muscimol was significantly increased at the injected site, whereas no significant alteration of [3H]muscimol binding was found in GP, SN, or CC. Scatchard analysis of striatal binding revealed that microinjection of KA significantly increased the affinity (KD) of GABA receptors on the injected (lesioned) side of the CS without affecting the total number of binding sites (Bmax) therein. This significant increase in [3H]muscimol binding, however, was eliminated by pretreating particulate fractions from the CS with Triton X-100, a non-ionic detergent. No statistically significant difference in amounts of [3H]muscimol binding was detected when the preparations from the KA treated and non-treated CS were preincubated with 0.05% Triton X-100, respectively. Scatchard analysis using CS preparations treated with 0.05% Triton X-100 revealed that the affinity of the GABA receptor was increased by treatment with Triton X-100, while the total number of binding sites (Bmax) was unchanged by this treatment. These results suggest that neuronal degeneration produced by KA in vivo and pretreatment of particulate preparations with Triton X-100 in vitro may increase the amount of specifically bound [3H]muscimol to CS preparations by a similar molecular mechanism. PMID- 6256484 TI - The extrusion of sodium ions from presynaptic nerve endings of rat cerebral cortex. AB - (Na+-K+) ATPase is present in synaptosomal preparations and it is assumed to represent the sodium-potassium pump. 10 microM-noradrenaline activates (Na+-K+) ATPase approximately 100%, but 50 microM-noradrenaline does not stimulate the rate of 22Na extrusion from synaptosomes. The results suggest that it is unlikely that the noradrenaline stimulation of (Na+-K+) ATPase is part of a feedback mechanism whereby released noradrenaline can influence the activity of the presynaptic sodium pump. PMID- 6256485 TI - 5'-nucleotidase in rat brain myelin. AB - Rat brain myelin showed substantial activity of 5'-nucleotidase. The specific activity in myelin was enriched two- to threefold over that in rat brain homogenates, and the total activity in myelin accounted for approximately 24% of the activity in the homogenates. The 5'-nucleotidase in the homogenates and in isolated myelin had optimum activity at pH 7.5--9.0, was stimulated by Mg2+ and Mn2+, and was inhibited by Co2+, Zn2+, EDTA, and EGTA. 5'-AMP, 5'-UMP, and 5'-CMP were the preferred substrates, and 5'-GMP was hydrolyzed at approximately one half the rate of the other mononucleotides. The very low rates of cleavage of beta-glycerophosphate and 2'-AMP ruled out any significant contribution of nonspecific phosphatase to the observed 5'-nucleotidase activity in myelin. The 5'-nucleotidase was inhibited by concanavalin A and was protected by alpha-methyl D-mannoside against inhibited by that lectin, suggesting that this enzyme in the CNS is a glycoprotein. It is concluded from these data, and from histochemical observations made in other laboratories, that the myelin sheath is one major locus of 5'-nucleotidase in the rat brain. PMID- 6256486 TI - Ultraviolet irradiation produces loss of saxitoxin binding to sodium channels in rat synaptosomes. AB - Ultraviolet irradiation (UV) has been shown to cause an electrophysiologically measured inactivation of the rapid, transient sodium conductance system in nerve. Tritiated saxitoxin ([3H]STX) was used as a structural probe to assess the possibility of a corresponding perturbation in the conformation of the STX binding site. UV irradiation caused an irreversible decrease in the total number of high-affinity [3H]STX binding sites in rat synaptosomes, while the dissociation constant of the remaining sites did not change. The receptor loss followed first-order kinetics, and the rate of loss was independent of temperature. The action spectrum for binding loss indicated a peak in spectral sensitivity near 280 nm. A22Na flux assay in irradiated synaptosomes directly demonstrated that [3H]STX binding sites and veratridine-stimulated, STX-blocked 22Na efflux had similar sensitivities to UV radiation. We conclude that the UV inactivation of functional channels includes a modification of the STX binding site structure. PMID- 6256487 TI - Subcellular distribution and developmental change of 2',3'-cyclic nucleotide 3' phosphohydrolase in the central nervous system of the myelin-deficient shiverer mutant mice. AB - Shiverer is an autosomal recessive mutant characterized by dysmyelination in the central nervous system. The myelin in the shiverer is devoid of the major dense line. The pattern of increase of 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase) in the various parts of central nervous system during postnatal development was identical with that of controls. Subcellular fractionation of the brain from shiverer showed that the recovery of CNPase activity of the P2A was only 14% of the control, but those of P2B and P3 were several times higher than the controls. The specificity activity of CNPase of the purified myelin and P2A from shiverer did not differ significantly from that of the controls. The combined P2 and P3 (P2 + P3) fraction was subjected to linear sucrose density gradient (0.32--1.3 M) centrifugation. By measuring CNPase activities of the fractions obtained after centrifugation, shiverer showed two peaks of CNPase activities in the sucrose gradient, although that of the control showed a single peak. The main peak obtained from shiverer was found in the region of higher sucrose concentration than that of the control, while a small peak was found in the region of lower sucrose concentration. PMID- 6256488 TI - A sensitive fluorometric assay for 2',3'-cyclic nucleotide 3'-phosphohydrolase. PMID- 6256489 TI - Activity of pyridoxamine as a substrate for brain pyridoxal kinase. AB - The substrate activity of pyridoxamine (PM) for brain pyridoxal (PL) kinase was examined in view of a recent report which indicated that PM was a poor substrate for this enzyme. Bovine brain PL kinase was shown by liquid chromatography to catalyze the phosphorylation of PM (Km = 65 microM). The identity of the reaction product, pyridoxamine 5'-phosphate, was confirmed by is ability to act as a substrate for liver pyridoxine (pyridoxamine) 5'-phosphate oxidase. The results, which indicate that PM is a good substrate for brain PL kinase, are consistent with the proposed role of intracellular phosphorylation in the uptake of vitamin B-6 brain tissue. PMID- 6256490 TI - Brain cyclic nucleotide responses to anesthesia with halothane delivered in air or purified oxygen. AB - Inhalation of either 0.5% or 1.0% halothane in air caused a slight decrease in the cAMP concentration in rat cerebral cortex and cerebellum. During recovery, concentrations returned to normal in 3 h, or less. In contrast, cGMP decreased sixfold in cerebellum, but increased twofold in cortex. Recovery time for cerebellum was several hours. When oxygen was used as the carrier gas for halothane delivery, cAMP in the cortex doubled, in striking contrast to the case with halothane in air. Oxygen alone had no apparent effect. The cGMP effect of halothane delivered in oxygen appeared the same as for halothane in air. Thus, the cAMP effects of brain halothane are related to the enrichment of oxygen. PMID- 6256491 TI - Dissociation of myelin from its 'enzyme markers' during ontogeny. AB - To avoid any loss of membranes, total particulate material prepared from the forebrain and spinal cord of rats of different ages was fractionated on linear sucrose gradients. Particle distribution, proteins and enzyme activities were measured. Beginning at early ages, optical density increases were observed around 0.60 M-sucrose, which corresponded to myelin deposition, and were expressed by the appearance of typical myelin proteins, which paralleled the peak activity of myelin-associated enzymes. During later development myelin proteins were found over a broad density range together with optical density shifts to higher (forebrain) and lower (spinal cord) values. In both regions myelin-associated enzymes shifted to heavier densities and were dissociated from the density region commonly considered to be compacted myelin. PMID- 6256492 TI - Heterogeneity of benzodiazepine receptors in the central nervous system demonstrated with kenazepine, an alkylating benzodiazepine. AB - Binding studies using the alkylating benzodiazepine kenazepine strongly suggest the existence of several populations of benzodiazepine receptors in the CNS. Kenazepine reacts noncompetitively and irreversibly with some receptors and competitively (reversibly) with others. Cerebellum contains the largest proportion (approx. 80%) of the noncompetitive type, while hippocampus and cortex contain a preponderance of competitive-type receptors (approx. 80 and 50%, respectively). The Hill coefficients for kenazepine are approx. 0.7 in cortex and cerebellum, and near unity in dorsal hippocampus. Different populations of benzodiazepine receptors may mediate different physiologic and pharmacologic effects in vivo. PMID- 6256493 TI - Cyclic guanosine monophosphate in primary cultures of glial cells. AB - Cyclic GMP was found in primary cultures of glial cells obtained by dissociation of newborn mouse brain hemispheres. Its basal level (0.52 pmoles/mg cell protein) was as high as that found in adult mouse brain cortex but 10 times lower than in cerebellum. When glia were grown in the presence of dBcAMP, astrocytes changed their morphology; cGMP level increased and reached about 8 to 10 times the basal value. This increase was dose dependant with cAMP and was enhanced by the presence of 5mM Theophylline. Two hypothesis are discussed, either a direct action oc cAMP on glial cGMP metabolism or an indirect one on the protein activator of cGMP phosphodiesterase. PMID- 6256494 TI - Evidence for the presence of CDP-ethanolamine: 1,2-diacyl-sn-glycerol ethanolaminephosphotransferase in rat central nervous system myelin. AB - Highly purified rat brain myelin isolated by two different procedures showed appreciable activity for CDP-ethanolamine: 1,2-diacyl-sn-glycerol ethanolaminephosphotransferase (EC 2.7.8.1). Specific activity was close to that of total homogenate and approximately 12-16% that of brain microsomes. Three other lipid-synthesizing enzymes, cerebroside sulfotransferase, lactosylceramide sialyltransferase, and serine phospholipid exchange enzyme, were found to have less than 0.5% the specific activity in myelin compared with microsomes. Washing the myelin with buffered salt or taurocholate did not remove the phosphotransferase, but activity was lost from both myelin and microsomes by treatment with Triton X-100. It resembled the microsomal enzyme in having a pH optimum of 8.5 and a requirement for Mn2+ and detergent, but differed in showing no enhancement with EGTA. The diolein Km was similar for the two membranes (2.5-4 x 10(-4) M), but the CDP-ethanolamine Km was lower for myelin (3-4 x 10(-5) M) than for microsomes (11 - 13 x 10(-5 M). Evidence is reviewed that this enzyme is able to utilize substrate from the axon in situ. PMID- 6256495 TI - Effects of N-ethylmaleimide treatment on the action potential Na+-ionophore of cultured neuroblastoma cells. AB - Treatment of murine neuroblastoma N18 cells with N-ethylmaleimide under conditions that favor diminution of membrane potential leads to a 65% increase in the rate of veratridine-stimulated, tetrodotoxin-sensitive Na+ uptake and to a 50% decrease in the concentration of veratridine required for half-maximal stimulation. This modification does not appear to occur in N18 cells having a normal membrane potential of approx. -40 mV. The data are consistent with the involvement of a sulfhydryl group in the Na+ channel inactivation gate and in the conformational change in this gate which results in closing of the channel. PMID- 6256496 TI - Distribution of GABA receptors in the rat cerebellum. AB - The distribution of GABA receptors in the cerebellum is not homogeneous. In comparison with detergent-treated membranes from the whole tissue the number of [3H]muscimol binding sites per mg protein (Bmax) is about doubled in preparations enriched in large fragments of the cerebellar glomeruli, and it is about one third in the dissected deep nuclei. On the other hand, the apparent affinity (Kd) is similar in the different preparations. Comparison of the results with earlier studies suggests a heterogeneity in cerebellar GABA receptors and/or their control. PMID- 6256497 TI - Modification of the rate of ouabain binding to (Na+ + K+)ATPase by lithium ions. AB - We report on the interactions of Li+, a congener of K+ with the (Na+ + K+)-ATPase from E Electricus as measured by their effects on the rate of [3H]-ouabain binding to this enzyme. Like K+, Li+ slows ouabain binding under both Type I (Na+ + ATP) and Type II (P1) conditions, but with lower affinity. In contrast to K+, the Li+ inhibition curve is hyperbolic, suggesting interaction at an uncoupled site. Also differing from the complete inhibition by high K+, a residual ouabain binding rate persists at high Li+. The interactions of Li+ and K+ are synergistic: the apparent K+ affinity increases 3 to 4-fold in presence of Li+. These results are consistent with the conclusion that Li+ interacts with only one of the two K+ sites and may be of interest in interpreting lithium pharmacology. PMID- 6256498 TI - Transient formation of superoxide radicals in polyunsaturated fatty acid-induced brain swelling. AB - The involvement of superoxide free radicals and lipid peroxidation in brain swelling induced by free fatty acids has been studied in brain slices and homogenates. The polyunsaturated fatty acids linoleic acid (18:2), linolenic acid (18:3), arachidonic acid (20:4), and docosahexaenoic acid (22:6) caused brain swelling concomitant with increases in superoxide and membrane lipid peroxidation. Palmitic acid (16:0) and oleic acid (18:1) had no such effect. Furthermore, superoxide formation was stimulated by NADPH and scavenged by the addition of exogenous superoxide dismutase in cortical slice homogenates. These in vitro data support the hypothesis that both superoxide radicals and lipid peroxidation are involved in the mechanism of polyunsaturated fatty acid-induced brain edema. PMID- 6256499 TI - Choline uptake by the neuroblastoma x glioma hybrid, NG108-15. AB - The neuroblastoma x glioma hybrid clone NG108-15 is able to release acetylcholine upon depolarization and form cholinergic neuromuscular synapses in culture. Normal functioning of cholinergic synapses is thought to be dependent on the ability of a neuron to take up extracellular choline, since neurons are unable to synthesize choline de novo. For these two reasons it became important to characterize the choline uptake system of NG108-15 cells. The uptake system appears to bear little if any resemblance to the Na+-dependent high-affinity choline uptake system normally associated with cholinergic neurons. Although the cells appear to possess both high- and low-affinity choline uptake systems, neither system is dependent on Na+ and uptake actually is increased about 60% by the substitution of sucrose for NaCl. Acetylcholine synthesis also is not dependent on Na+, since sucrose, substituted for NaCl, also stimulates acetylcholine synthesis. Changes in the concentrations of the other ions in the uptake medium have little effect on uptake, with the exception that elevated Ca2+ or Mg2+ reverses the stimulation of choline uptake produced by substitution of sucrose for NaCl. Choline uptake is inhibited by hemicholinium-3, but only at high concentrations of the drug (IC50 = 30-80 microM). The metabolic poisons cyanide and iodoacetate inhibit uptake by only 30-40%. Growth of the cells in N6,O2' dibutyryladenosine-3',5'-cyclic monophosphate, which promotes functional and morphological differentiation of the cells, decreased slightly the total amount of choline taken up but had no additional effect on the uptake system. Thus, it appears that NG108-15 cells are capable of forming functional cholinergic synapses with muscle cells even though the neuroblastoma does not possess the high-affinity choline uptake system normally associated with cholinergic neurons. PMID- 6256500 TI - [3H]Spiroperidol binding in rat striatum: two high-affinity sites of differing selectivities. AB - [3H]Spiroperidol binding to homogenates of rat striatum is saturable and shows either monophasic or biphasic saturation isotherms under specified conditions. In poorly washed membrane fragment preparations, saturation isotherms of [3H]spiroperidol binding are monophasic, revealing an apparently homogeneous set of sites with KD 0.6 +/- 0.3 nM and density 440 +/- 80 fmol/mg protein. However, equilibrium displacement studies of [3H]spiroperidol binding at this site indicate an alpha-adrenergic component in addition to the previously described dopaminergic component. In thoroughly washed membrane fragment preparations, saturation isotherms are clearly biphasic, showing an additional high-affinity site with an approximate KD of 24 +/- 10 pM and an approximate density of 110 +/- 20 fmol/mg protein at a protein concentration of 2.0 mg/ml. Selectivity at this site appears classically dopaminergic, suggesting that the lower affinity site is the primary source of the alpha-adrenergic component of spiroperidol binding. PMID- 6256501 TI - Comparison of 2',3'-cyclic nucleotide 3'-phosphodiesterase and the major component of Wolfgram protein W1. AB - Wolfgram protein preparations from myelin are heterogeneous mixtures having major components with molecular weights in the 43,000 to 60,000 range. Through the use of an SDS-slab gel electrophoretic system of high resolving power, the Wolfgram 1 (W1) component described by Nussbaum et al. (1977) has been resolved into two components; bovine W1a and W1b proteins are found to have mobilities identical to those of the two 2',3'-cyclic nucleotide 3'-phosphodiesterase (2'3'-CN 3'-ase) components, CNa and CNb (Drummond, 1979). Crossed immunoelectrophoresis with bovine 2',3'-CN 3'-ase demonstrates that CNa and CNb are antigenically indistinguishable. Rat and bovine Wolfgram proteins W1a and W1b, but not the W2 proteins, display cross reactivity with antiserum directed against bovine 2',3' CN 3'-ase. Chymotryptic and Staphylococcus aureus V8 protease peptide profiles indicate structural similarities between proteins CNa-W1a and CNb-W1b. It is concluded that an inactivated form of 2',3'-Cn 3'-ase is a major component of Wolfgram protein W1. These results are consistent with the studies on the histochemical localization of rat W1 protein by Roussel et al. (1977, 1978). PMID- 6256502 TI - Studies on the Wolfgram high molecular weight CNS myelin proteins: relationship to 2',3'-cyclic nucleotide 3'-phosphodiesterase. AB - Evidence is presented that the major protein components of the high molecular weight CNS myelin proteins designated as the Wolfgram protein doublet (W1 and W2) contain the enzyme 2',3'-cyclic nucleotide 3'-phosphodiesterase (EC 3.1.4.37, CNP). CNP is a basic hydrophobic protein containing about 830 to 840 amino acid residues. When electrophoresed on SDS polyacrylamide gels, CNP appears as a protein doublet, separated by a molecular weight difference of about 2500-3000 in bovine, human, rat, guinea pig, and rabbit. A similar protein doublet has been identified as the Wolfgram proteins W2 and W1 in myelin and in the chloroform methanol-insoluble pellet obtained from myelin. Moreover, the relative Coomassie blue staining intensity of the CNP2 plus CNP1 protein doublet among the species examined was remarkably similar to that observed for electrophoresed myelin and chloroform-methanol-insoluble pellet derived from myelin. Antisera raised against purified bovine CNP recognized the W1 and W2 proteins isolated from bovine and human brain. The amino acid composition of pure bovine CNP is presented and compared with the compositions of several rat and bovine Wolfgram proteins obtained by other investigators. Our electrophoretic, compositional, and immunological data support the contention that the enzyme CNP is a major component of the Wolfgram protein doublet. PMID- 6256503 TI - Quantitative relationships of five putative neurotransmitter receptor sites in rat hippocampal formation. AB - The hippocampus is well suited for studies of the interrelationships of various neurotransmitter systems in the CNS by reason of its simple laminated organization, defined connections, and variety of identified neurotransmitters. We have studied the biochemical and pharmacological properties of five radiolabeled ligand binding sites in a membrane fraction prepared from rat hippocampal formation. These binding sites are thought to identify recognition sites for neurotransmitter receptors. The rank order of ligand binding sites is [3H]muscimol > [3H]quinuclidinyl benzilate > [3H]dihydroergocryptine > [3H]dihydroalprenolol > 125I-labeled alpha-bungarotoxin. All ligands have a single, saturable, high-affinity binding site. Pharmacological characterization of the ligand binding sites indicates properties consistent with the identification of these sites as neurotransmitter receptors. PMID- 6256505 TI - Short-term tissue culture observations of experimental primary and transplanted nervous system tumors. AB - Tumors of the central and peripheral nervous system were induced in BD-IX rats and transplanted serially. Both primary and transplanted tumors in different generations were cytologically analyzed, using primary explants in vitro. Four hundred and thirty single tumors were examined in vitro over th period 1969 to 1977, using the following methods: conventional aniline staining, special silver impregnation, supravital observation of cells by phase contrast microscopy, locomotion studies with time-lapse cinematography, and ultrastructural analysis from transmission and scanning electron microscopy. Cells grown in vitro were subdivided into the following groups, according to their morphology: (1) Apolar cells: Round cells only observed in rare tumors of the nasal cavity and sporadically in transplanted neurinomas; they are thought to represent cells from the reticular variant of neurinoma in the latter. (2) Bipolar cells occurred in two forms: As bipolar fibroblasts and as slender bipolar cells observed in explants of malignant neurinomas. The latter cells grow in parallel arrangements; their tentative interpretation as Schwann cells is consistent with their description in human neurilemomas. (3) Semipolar cells with one clear-cut edge and a broad ruffled membrane opposite. They are described as fibroblasts in the course of locomotion. (4) Multipolar cells, observed in several forms in primary and transplanted gliomas exclusively. Variants with long processes were seen in the first passages of intracerebrally transplanted tumors only; in later generations, all cells had short branching processes and little cytoplasm. Conclusions concerning the cytologic derivation of experimental tumors are discussed. PMID- 6256504 TI - Effects in vitro of serum from patients with Landry-Guillain-Barre syndrome of alcoholic peripheral neuropathy on outgrowth of rat dorsal root ganglia. AB - Cultures of three-day-old rat dorsal root ganglia were grown in control media containing human cord serum or in experimental media containing serum from patients with Landry-Guillain-Barre syndrome, alcoholic peripheral neuropathy, or normal adults. Analysis of variance in control cultures showed that there was a falloff of mean outgrowth length during active myelination by fourteen days, while cultures grown in the three experimental media had a greater outgrowth length and did not form myelin. PMID- 6256506 TI - Structural and biochemical effects of essential fatty acid deficiency on peripheral nerve. AB - The effect of postweaning essential fatty acid (EFA) deficiency on the peripheral nerve was studied in groups of rats. At 325 days, the characteristic biochemical changes of EFA deficiency were present in isolated peripheral myelin, although to a lesser degree than reported in non-neural tissues. There was no significant difference between control and deficient groups in number or size distributions of myelinated fibers (MFs) in muscle and sensory nerves, in the incidence of teased fiber abnormalities, in rates of axonal transport of dopamine-beta hydroxylase and acetylcholinesterase, or in conduction velocity and compound action potentials of peripheral nerve in vivo or in vitro. Four weeks after a standard sciatic crush injury, the median MF diameter in regenerated peroneal nerves was significantly smaller in EFA-deficient rats than in control rats, but this difference was no longer significant at 18 weeks. At 18 weeks, EFA-deficient and control regenerated nerves showed similar myelin periodicity and relationship of axonal area to number of myelin lamellae. We conclude that acquired EFA deficiency in the rat leads to biochemically abnormal peripheral myelin, but that this state is unaccompanied by clinical, physiological, or morphological evidence of neuropathy. PMID- 6256507 TI - Pharmacological dissection of pyloric network of the lobster stomatogastric ganglion using picrotoxin. AB - 1. Picrotoxin (PTX) (10(-7)-10(-6) M) completely blocked most inhibitory synapses in the pyloric pattern generator of the lobster (Panulirus interruptus) stomatogastric ganglion. The sensitivity of synapses from most classes of identified neurons was examined. Blockade was at least partly reversible with prolonged washing. 2. The synapses from pyloric dilator (PD) neurons were the only inhibitory synapses that picrotoxin failed to block completely. 3. A correlation is derived that brief, fast-rise inhibitory postsynaptic potentials (IPSPs) are picrotoxin sensitive, whereas a slow rounded component of IPSPs from PD neurons is not picrotoxin sensitive. 4. Picrotoxin caused specific changes in the pattern of the motor rhythm produced by the 16-cell pyloric network. This sheds some light on the functional role of particular synapses in the pyloric generator. 5. The endogenously bursting neurons (PD and anterior burster (AB)), which drive the pyloric rhythm, kept a similar burst rate. 6. Under picrotoxin, the pyloric "follower" neurons all moved to later phase relative to the "driver" group. Some normally antagonistic cells, related by reciprocal inhibitor connections, became in-phase. These and other pattern changes could be related to blockade of particular synapses. 7. The pyloric rhythm was still quite recognizable under picrotoxin despite the drastically altered circuitry of the synaptic network. This supports the idea that periodic inhibition from the PD driver neurons plays a primary role in creating the pyloric pattern. PMID- 6256508 TI - Mechanisms underlying pattern generation in lobster stomatogastric ganglion as determined by selective inactivation of identified neurons. I. Pyloric system. AB - 1. Four factors contribute to pattern generation in the pyloric network of the lobster stomatogastric ganglion. These are: a) endogenously oscillating neurons; b) synaptic network properties; c) nonlinear cellular properties, including the generation of plateau potentials; and d) excitatory input from the commissural ganglia. The roles and relative importance of these factors were investigated with a new technique for inactivating single specific identified neurons. 2. In stomatogastric ganglia in which the excitatory input is left intact, a) pattern generation continues when any cell or pair of cells other than the endogenous bursters are inactivated, b) pattern generation also continues when the endogenous bursters are inactivated, c) pattern generation ceases when the endogenous bursters plus one other particular cell are inactivated. This cell, although not an endogenous burster, displays a strong tendency to generate plateau potentials. 3. In stomatogastric ganglia that have been isolated from excitatory input, a) pattern generation continues when any cell or pair of cells other than the endogenous bursters are inactivated, b) pattern generation ceases when the endogenous bursters are inactivated. 4. Some of the inputs to the stomatogastric ganglion normally fire in bursts. However, their potentiation and acceleration of the output pattern are also produced by tonic stimulation of the nerve. The effect of one of those inputs is mimicked by bath application of dopamine to the stomatogastric ganglion. 5. The roles and importance of the three most important factors were qualitatively summarized in a chart specifying the activity of the network as a function of its intactness. PMID- 6256509 TI - Mechanism of long-lasting synaptic inhibition in Aplysia neuron R15. AB - 1. Long-lasting inhibition is a synaptically mediated response found in certain molluscan nerve cells that fire action potentials in bursts. It is elicited by repetitive stimulation of a presynaptic nerve and may last for minutes or hours after stimulation. 2. Voltage-clamp techniques were employed to measure the voltage dependence of the synaptically elicited current. Current-voltage curves were obtained by stepping or sweeping the voltage over the range -40 to -120 mV. 3. Long-lasting inhibition was found to be mediated by two separate conductance mechanisms. A component that reverses near -80 mV is most prominent at times up to 5 min following stimulation. A component with no reversal potential between 40 and -120 mV predominates at later times. 4. The reversible component is attenuated by reducing the intensity of stimulation of the presynaptic nerve, by injection of TEA into the postsynaptic cell, or by activation of a potassium conductance with serotonin prior to stimulation of the nerve. Thus, the reversible component appears to be mediated by an increase in potassium conductance. 5. The effects of the nonreversible component measured in the soma appear to be too large to attribute it to a conductance change that is electrically "distant" from the soma. It is attenuated by turning off a resting inward ion conductance with dopamine prior to stimulation of the nerve. It is not affected by short exposure to ouabain, but is attenuated by longer exposures that reduce the sodium and calcium gradients. Thus, the nonreversible component may be mediated by a decrease in voltage-dependent inward current flow carried by sodium or calcium. PMID- 6256510 TI - Immunobiology of primary intracranial tumors. Part 4: levamisole as an immune stimulant in patients and in the ASV glioma model. AB - Levamisole was evaluated as an immune stimulant in a randomized controlled study of patients with anaplastic gliomas, who had undergone surgical resection and who were also treated with radiotherapy and BCNU chemotherapy. Of 102 patients placed into the study, 85 were determined to comprise the adequately treated group (ATG): a full course of radiotherapy and two cycles of BCNU chemotherapy. Within the ATG, those patients who received levamisole did not demonstrate significantly different serial delayed hypersensitivity reactions, peripheral blood lymphocyte and T-cell counts, or serum IgM levels, compared to those patients not receiving levamisole. There was no significant difference in survival times of the two groups. Studies utilizing the avian sarcoma virus-induced glioma in rats also showed no improvement in survival with levamisole stimulation as the only immune agent, but the combination of active immunization and adjuvant stimulation with bacillus Calmette-Guerin plus levamisole was found to be therapeutically effective in this model and will be used in future pilot studies of active immunization in patients. PMID- 6256511 TI - Quantitation of experimental canine infarct size using multipinhole single-photon tomography. AB - A four-pinhole longitudinal tomographic system, with collimator and software, was developed for a standard-field portable scintillation camera. This system was used with technetium--99m pyrophosphate (Tc-PPi) to quantify the volume of infarcted myocardium in 27 dogs with experimental myocardial infarcts. These were induced by ligation of the left anterior descending (LAD) or the circumflex coronary artery. Tomographic estimations of scintigraphic infarct size agreed well with postmortem findings when the circumflex group (r = 0.87) and LAD group (r = 0.83) were considered separately, but the correlation fell when the groups were pooled (r = 0.73). Whereas multipinhole tomography extends Tc-PPi infarct sizing capability in animals to include posterior and subendocardial infarcts as well as anterior lesions, the tomographic sections contain enough blur artifacts to lower the sizing accuracy of the method. The main advantage of the technique may well be its ability to aid in detection and location of small myocardial infarcts. PMID- 6256512 TI - [Action sites of morphine--effects on dopaminergic and GABA-containing neurons in the basal ganglia]. PMID- 6256513 TI - The effect of polybrominated biphenyl on infants and young children. AB - The effects of PBB on 33 children born between September 1, 1973, and December 31, 1975, were evaluated in September, 1977. These children, born to families who lived on quarantined farms, were compared to 20 children who were not exposed to PBB. The birthdate interval was selected to obtain children who were exposed in utero or in early infancy or both, the two time periods when damage to developing tissues and organ systems should have been maximal. The results of these studies failed to identify any effects on physical growth, physical examination, or neurologic assessment, although the parents indicated by historical review that the exposed children had had more illnesses, especially respiratory, than had the control children. There were some indications of an inverse relationship between PBB fast level and performance on selected developmental tests. PMID- 6256514 TI - Structure-activity relationships of pyrrole amidine antiviral antibiotics III: preparation of distamycin and congocidine derivatives based on 2,5-disubstituted pyrroles. AB - Isomers of distamycin A and tripyrrole congocidine containing 2,5-disubstituted pyrroles were synthesized along with distamycin and congocidine homologs containing a single pyrrole ring. Selected compounds were evaluated for their cytotoxicity and antiviral activity. All of the tripyrrole derivatives tested in this series were nontoxic but were less active than distamycin A. The monopyrrole derivative, N-methyl-5-nitropyrrole-2-carboxamido-beta-propionamidine hydrochloride, was nontoxic and was almost as active antivirally as distamycin A. PMID- 6256515 TI - Synthesis and structure--activity relationship of a pyrimido[4,5-d]pyrimidine derivative with antidepressant activity. AB - The synthesis and antidepressant properties of a new pyrimido[4,5-d]pyrimidine are described. Spectral data determined in solution and in the solid state allowed establishment of the relationship between the activity and the conformation of the molecule. The spatial structure seems to be in accordance with a possible binding at the presynaptic alpha-receptor sites. PMID- 6256516 TI - Potentiation of responses to adrenergic nerve stimulation in isolated rat atria during chronic tricyclic antidepressant administration. AB - Several weeks of tricyclic antidepressant administration are required to effectively reverse depression. To determine whether there are adaptive changes in andrenergic nerve function which correspond to the clinical onset of antidepressant action, the endogenous norepinephrine content, [3H]norepinephrine uptake and retention, responses to exogenous norepinephrine and the release of norepinephrine during field stimulation were studied using left atrial strips isolated from rats treated with either acutely or chronically with tricyclic antidepressants. Desipramine, nortriptyline, chlorimipramine and iprindole were administered to rats, 10 mg/kg i.p., twice daily. After 14 days of drug administration, the responses to field stimulation were potentiated markedly by all four tricyclics. In contrast, 1 day of tricyclic treatment had only slight potentiating effects. When phenoxybenzamine, 10(-7) M, was added to the organ bath in order to block the inhibitory presynaptic alpha receptor, the responses of control atria and atria from rats treated for 1 day with desipramine were potentiated but those of atria treated for 21 days with desipramine were not potentiated. The development of presynaptic alpha receptor subsensitivity during chronic tricyclic administration would explain these findings. Other possible explanations were also investigated. The uptake and retention of [3H]norepinephrine was markedly inhibited to a similar degree of either 1 or 14 days of desipramine or nortriptyline administration. One day of chlorimipramine treatment decreased the amount of [3H]norepinephrine taken up and retained by left atrial strips, and after 14 days of treatment decreased the amount further. In contrast, neither 1 nor 14 days of iprindole administration had any effect on the uptake and retention of [3H]norepinephrine. These data indicate that the potentiation of the responses to field stimulation cannot be explained by the inhibition of norepinephrine uptake. The inotropic response to exogenous norepinephrine was not altered by any duration of administration of any of the four tricyclics studied. Furthermore, the endogenous norepinephrine content of atria did not change after as many as 21 days of desipramine administration. The present results indicate that the potentiation of the effects of adrenergic nerve transmission during chronic tricyclic administration is the result of an increase in norepinephrine release which occurs due to the development of presynaptic alpha receptor subsensitivity. The time course of development of presynaptic receptor subsensitivity corresponds well with the onset of clinical activity of these drugs. PMID- 6256517 TI - Interaction of calcium and microtubules in the action of cyclic AMP on the toad urinary bladder. AB - Involvement of microtubules in the cellular action of vasopressin was studied by physiological and biochemical procedures. The inhibitory effect of 10(-4) M colchicine on the hydro-osmotic response of the toad bladder to 2 mM cyclic AMP was completely blocked by an increase in the concentration of calcium in the serosal bathing medium from 1 to 8 mM. Most of the colchicine-binding activity of extracts of the bladder epithelial cells was recovered by DEAE-Sephadex chromatography in a procedure similar to that used to isolate tubulin of bovine brain. Sodium dodecyl sulfate urea and urea gel electrophoresis of the DEAE Sephadex fraction from the bladder epithelial cells yielded bands that corresponded to those of bovine brain tubulin. When 8 mM CaCl2 was present in an incubation mixture, the binding of colchicine to tubulin from the bladder epithelial cells and bovine brain was significantly inhibited. However, 1 mM CaCl2 did not affect the binding of colchicine to tubulin. Although the present study supports the concept that microtubules and calcium play an important role in the cellular action of vasopressin on the toad urinary bladder, the mechanism by which calcium blocks the inhibitory effect of colchicine on the hydro-osmotic response to cyclic AMP could not be elucidated. PMID- 6256518 TI - Tolerance and disposition of tetrahydrocannabinol in man. AB - The hypothesis was tested that the development of tolerance in man to the pharmacological effects of delta 9-tetrahydrocannabinol (THC) is due in part to changes in metabolism and disposition. Tolerance developed in six subjects following p.o. administration of 30 mg of THC every 4 hr for 10 to 12 days. Evaluation of THC pharmacokinetics was based on plasma levels of unchanged THC following i.v. administration of [14C] THC before and after the chronic p.o. THC. Development of tolerance was paralleled by pharmacokinetic changes: 1) average total metabolic clearance and the initial apparent volume of distribution increased from 605 to 977 ml/min and from 2.6 to 6.4 liters, respectively; 2) steady-state volume of distribution, averaging 684 liters, was unaltered; 3) the majority of model-dependent pharmacokinetic parameters as well as the time course of total metabolites in plasma were unchanged; 4) the percent dose excreted in urine decreased from 23.2 to 17.5%, but total elimination (urine plus feces) was not significantly changed; and 5) metabolites were rapidly formed (t 1/2 = 2.8 4.4 min), but slowly eliminated (t 1/2 = 49-53 hours) because of extensive protein binding. Renal clearance values of total metabolites were surprisingly low (maximum of 18-20 ml/min) and decreased with time (approximately 1 ml/min after 4-5 days), indicating the accumulation of highly bound metabolites. We conclude that such pharmacokinetic and metabolic changes cannot account for the development of tolerance to the cardiovascular, psychological and skin hypothermic effects of THC. PMID- 6256519 TI - Presynaptic and postsynaptic neuromuscular effects of a specific inhibitor of acetylcholinesterase. AB - Previous studies have shown indirectly that the neuromuscular effects of nonselective cholinesterase inhibitors are mediated through the inhibition of acetylcholinesterase (AChE). To test this hypothesis more directly we studied the effects of the specific inhibitor of AChE, BW 284c51, at the neuromuscular junction of rat diaphragms. BW 284c51 inhibits AChE in a dose-dependent partially reversible manner at all concentrations tested (10(-9) to 10(-4) M). Maximum inhibition was never greater than 92%. The drug increased miniature end-plate potential (MEPP) amplitude and prolonged half-decay time at 10(-7) and 10(-6) M. However, BE 284c51 had no effect on the resting membrane potential at any concentration. BW 284c51 at 10(-7) M reversibly increased MEPP frequency by almost 4-fold. There was a 2-fold increase in the occurrence of giant MEPPs in the presence of BW 284c51. The quantum content (m) of the end-plate potential was increased in 10(-7) M BW 284c51 as were end-plate potential amplitude and quantum size (q). Animals injected subcutaneously with 10 mg/kg of BW 284c51 displayed typical signs of AChE inhibition including salivation, whole body tremor and prostration. Spontaneous muscle fasciculation was more noticeable after in vivo injection of BW 284c51 than after in vitro administration. Furthermore, MEPP frequencies were considerably faster when the drug was injected in vivo than when applied in vitro. The data are discussed with respect to the hypothesis that inhibition of AChE causes presynaptic as well as postsynaptic effects. PMID- 6256520 TI - Opiate binding sites in the retina: properties and distribution. AB - The presence of opiate binding sites in rat retina was confirmed and their properties and distribution were investigated. Etorphine, naloxone and methionine enkephalin exhibit high affinity, saturable binding to retinal membrane preparations. Scatchard analysis of the binding data yielded linear plots for each ligand. The P1 subcellular fraction contains the greatest density of sites per milligram of protein. The response of the binding of all ligands to sodium ions was similar in the retina to that observed in the brain. Competition experiments using naloxone and methionine enkephalin indicated that a homogeneous class of binding sites exists in the rat retina. Opiate binding sites were also demonstrated in the retina of cow, toad and skate. Methionine enkephalin-like immunoreactivity was not clearly detectable in rat retina but was present in toad retina. The physiological role of the opiate binding sites in the retina remains to be elucidated. PMID- 6256521 TI - The role of norepinephrine in the regulation of fluid absorption in the rat proximal tubule. AB - In order to investigate the possibility of a direct effect of adrenergic transmitter on tubular fluid absorption, we have studied the effects of norepinephrine and phenoxybenzamine on fluid absorption in the proximal convoluted tubule of the rat kidney. Net fluid absorption (Jv) was determined in the same proximal convoluted tubule before and after addition of norepinephrine or phenoxybenzamine while the tubular lumen and peritubular capillaries were simultaneously microperfused in situ. When the tubular lumen was perfused with Ringer's solution and the peritubular capillaries were perfused with albumin Ringer's solution, Jv was 2.85 +/- 0.25 nl/min X nm. Addition of 2 X 10(-6) M norepinephrine to the capillary perfusate caused at 30% increase in Jv which could be reversed by removing the adrenergic transmitter. The effect of norepinephrine was dose dependent with the maximal increase of Jv observed at a concentration of 10(-5) M. Addition of 2 X 10(-6) M phenoxybenzamine to the capillary perfusate caused a 16% decrease in Jv while the simultaneous administration of norepinephrine and phenoxybenzamine to the capillary perfusate caused a 25% decrease in Jv. On the other hand, there was no effect observed on Jv when either norepinephrine or phenoxybenzamine was added to the luminal perfusate. These results suggest that adrenergic nerves may participate in the regulation of tubular fluid absorption through the direct action of norepinephrine on alpha adrenergic receptors located on the basolateral membrane of proximal tubular cells. PMID- 6256522 TI - Differential effects of the anticonvulsants phenobarbital, ethosuximide and carbamazepine on neuromuscular transmission. AB - The actions of the anticonvulsants phenobarbital, ethosuximide and carbamazepine were examined electrophysiologically at the frog neuromuscular junction. Phenobarbital reduced miniature end-plate potential (MEPP) amplitude, did not significantly affect end-plate potential amplitude and increased quantal content. Ethosuximide decreased MEPP and end-plate potential amplitudes proportionally; quantal content was unchanged. Carbamazepine decreased end-plate potential amplitude more than MEPP amplitude; quantal content was decreased. In a solution containing elevated (7.5 mM) K+, phenobarbital and carbamazepine increased MEPP frequency, whereas ethosuximide had no effect. Carbamazepine had to be dissolved in a solvent, propylene glycol, which was shown to produce small, but sometimes statistically significant, alterations in the measured parameters of neuromuscular transmission. The results show that all three of these anticonvulsants depress postjunctional sensitivity to released acetylcholine producing parallel dose-response curves for MEPP amplitude inhibition. These experiments also show that these drugs exhibit different mechanisms of action with respect to nerve-stimulated neurotransmitter release from nerve terminals at the neuromuscular junction: phenobarbital enhances acetylcholine release, ethosuximide has no effect and carbamazepine decreases transmitter release. PMID- 6256524 TI - Identification of two benzodiazepine binding sites on cells cultured from rat cerebral cortex. PMID- 6256523 TI - Cocaine and amphetamine antagonize the decrease of noradrenergic neurotransmission elicited by oxymetazoline but potentiate the inhibition by alpha-methylnorepinephrine in the perfused cat spleen. PMID- 6256525 TI - Centrally induced cardiovascular and sympathetic nerve responses to bradykinin in rats. AB - Central actions of bradykinin were studied by recording blood pressure and sympathetic nerve activity from the body of a recipient rat whose head was vascularly isolated and perfused by a donor rat. Intracarotid injections of bradykinin had biphasic effects consisting of initial inhibition followed by more prolonged stimulation. Initial vasodepression and sympathetic inhibition disappeared after intracerebroventricular injection of 6-hydroxydopamine. On the other hand, the secondary pressor response and its attendant sympathetic hyperactivity were reduced after inhibition of prostaglandin synthesis with indomethacin, and conversely, augmented after administration of the prostaglandin precursor, arachidonic acid. Pressor responses elicited by intracerebroventricular injection of bradykinin in awake rats were also inhibited by indomethacin. These results indicate that bradykinin has at least two centrally induced actions on blood pressure: an initial vasodepression caused by release of endogenous norepinephrine which activates alpha adrenergic vasodepressor mechanisms in supramedullary centers, and a secondary pressor effect that may be mediated via release of endogenous prostaglandins. PMID- 6256526 TI - Effects of prolonged treatment with lithium and tricyclic antidepressants on discharge frequency, norepinephrine responses and beta receptor binding in rat cerebellum: electrophysiological and biochemical comparison. PMID- 6256528 TI - Calcium in synaptic transmission. PMID- 6256527 TI - Maturation of sympathetic neurotransmission in the rat heart. VII. Suppression of sympathetic responses by dexamethasone. AB - Effects of dexamethasone on development of sympathetic nerve function in the heart were evaluated by giving 1 mg/kg of dexamethasone s.c. daily for several days beginning the day after birth. Dexamethasone interfered with tyramine- and isoproterenol-induced tachycardia in the neonates but did not cause alterations in development of a marker for presynaptic sympathetic nerve terminals (synaptic vesicle uptake of [3H] norepinephrine) nor of postsynaptic beta adrenoceptor binding of [3H]dihydroalprenolol; the deficit was also unrelated to general cellular effects of the hormone. These data suggest that the subnormal chronotropic responses of the heart to sympathetic stimulation in dexamethasone treated neonatal rats result from uncoupling of receptors from the organ response. The effects of dexamethasone on cardiac responses were specific to the neonate, as mature rats given dexamethasone did not show suppression of cardiac sympathetic action. Neonatal dexamethasone treatment also produced a deficit of adrenomedullary development with deficiencies in catecholamine levels and in catecholamine biosynthetic enzymes; deficits in phenylethanolamine N methyltransferase activity persisted into young adulthood. PMID- 6256529 TI - Ion migration and inactivation in the calcium channel. AB - 1. Calcium conduction has been studied under voltage clamp in isolated nerve cell bodies of Helix aspersa. A suction pipette method was used to produce internal perfusion and low access resistance to the cell's interior. 2. Ca current does not obey the independence principle and saturates with increasing extracellular Ca concentration. The effect is voltage-dependent. 3. The unit conductance for the Ca channel is between 10(-12) and 10(-13) S, values consistent with impeded conduction. 4. Inactivation is partly dependent upon an increase of intracellular Ca activity due to Ca current. However, a component remains after the increase in [Ca]i has been prevented with EGTA. 5. The Ca channel may have two open states or there may be two sets of Ca channels. PMID- 6256530 TI - Attempts at localizing calcium in relation to synaptic transmission: an X-ray microanalytical study. AB - 1. In view of the importance of calcium in triggering the transmitter secretion during nerve stimulation or depolarization, the localization of calcium binding sites was studied in stimulated nerve endings that were fixed in calcium containing s-collidine buffered paraformaldehyde solution. 2. In cholinergic synapses, such as the superior cervical ganglion of cat, the myoneural junction of rat diaphragm and the electric organ of Torpedo marmorata, a stimulation dependent accumulation of calcium was found in the mitochondria of presynaptic nerve endings. 3. In synaptosomes prepared from rat cerebral cortex, the activity dependent accumulation of calcium in mitochondria of pinched off nerve endings was also observed. The mitochondrial accumulation of calcium in synaptosomes was dependent on ATP, temperature and could be inhibited by quercetin. 4. In stimulated synapses, only the mitochondria seemed to accumulate calcium in appreciable amounts, whereas other intra-terminal structures, such as the smooth endoplasmic reticulum and synaptic vesicles were devoid of calcium. PMID- 6256531 TI - Transmission in the squid giant synapse: a model based on voltage clamp studies. AB - 1. Voltage clamp studies were performed in squid giant synapse after blockage of the voltage-dependent sodium and potassium conductances. 2. Presynaptic depolarization under these conditions demonstrates the presence of voltage dependent calcium conductance change for the duration of the voltage step, and a tail current at the break of the pulse. 2. This calcium current triggers a postsynaptic response which can be measured directly at the postsynaptic fiber. 4. These voltage clamp experiments have allowed the development of a mathematical model that describes the kinetics of the calcium current and the relationship between calcium current and transmitter release. PMID- 6256532 TI - Action of calcium ions on acetylcholine-sensitive channels in Aplysia neurones. AB - 1. This work deals with the effects of external divalent ions on the values of the mean open time, tau, and of the elementary current, iel, of channels activated by acetylcholine in Aplysia neurones. The action of Ca is mainly considered. 2. Ca ions were found to prolong tau and decrease iel under various experimental conditions. In isotonic Ca solution, tau is 12 times larger than in isotonic Na solution (divalent free sea water). On the other hand, iel is about 8 times smaller in the first solution than in the second. 3. A quantitative analysis of these effects is presented. PMID- 6256534 TI - Group therapy in a pain management program. PMID- 6256533 TI - Interpersonal trust, life events and coping in an ethnic adolescent population. PMID- 6256536 TI - Couples group treatment of chronic marital dysfunction. PMID- 6256537 TI - Psychosomatic problems in the People's Republic of China. PMID- 6256535 TI - Community mental health: a course for caretakers. PMID- 6256539 TI - Absurdity as an intervention in the impotence impasse. PMID- 6256538 TI - The evaluation of co-leading a gestalt group. PMID- 6256540 TI - An evening diversional activity program for psychiatric patients. PMID- 6256541 TI - Juvenile prostitution: a nursing perspective. PMID- 6256542 TI - Quality assurance: focus on environmental perceptions of psychiatric patients and nursing staff. PMID- 6256543 TI - Disability among the elderly after myocardial infarction: a 3-year follow-up. PMID- 6256544 TI - [Computed tomography investigation of hepatic carcinomas (author's transl)]. AB - Computed tomography examinations, using a second generation Acta 200 FS apparatus, were conducted on 28 occasions in 25 patients with hepatic carcinoma. Before injection, the tumor is usually of low density, to a small degree in many cases, and is heterogeneous and has indefinite limits. The sensitivity of the method is 96 p. cent. A precise study of the localization of the tumor was possible in only 11 cases, and a definite diagnosis was made in 64 p. cent. The method was only moderately effective in assessing the degree of regional extension. When compared with other methods for the investigation of the liver (scintigraphy, ultrasonography, arteriography), computed tomography shows no superiority over ultrasonography which should be employed for the initial examination. PMID- 6256545 TI - Different patterns of cyclic AMP accumulation in rat corpora lutea after LH stimulation in vitro and in vivo. AB - Tissue levels of cyclic AMP were measured in rat corpora lutea at various times after administration of LH in vitro and in vivo. In-vitro addition of LH produced more pronounced accumulation of cyclic AMP in very young corpora lutea (1-day old) than in the older corpora lutea (3- and 7-day-old). When LH was administered in vivo the highest accumulation of cyclic AMP was seen in the older corpora lutea (7- and 3-day-old). PMID- 6256546 TI - LH receptors in ovine corpora lutea in relation to various physiological states and effects PGF-2 alpha on LH-induced steroidogenesis in vitro. AB - The LH binding properties (determined using tritiated methylated LH) and the in vitro steroidogenic activity of CL from ewes in the oestrous cycle or early pregnancy (Day 18) were compared. No significant alteration in the Kd values was observed. However, the number of sites was maximal at Day 10 of the cycle and in early pregnant animals which had not been pregnant for at least 3 months (dry ewes). Non-lactating or suckling ewes had half the numbers of binding sites. The increase of the number of receptor sites was accompanied by a steroidogenic response at lower LH concentration. During incubation or superfusion for 5 h, a refractoriness to LH stimulation appeared after 1 h with high LH concentrations and after 3 h with low concentrations. The opposite effect of the addition of indomethacin or PGF-2 alpha suggests the intervention of PGs in this phenomenon. PMID- 6256547 TI - Nicotine and its influence on the female reproductive system. PMID- 6256548 TI - Ratio of unconjugated to total estriol in uncomplicated third-trimester pregnancy. AB - The serum unconjugated estriol, as a percent of total estriol, has been determined in third-trimester pregnancies studied longitudinally. The unconjugated fraction in any specific sample ranged from 4.1% to 21.6% of the total. The mean percent unconjugated estriol in 34 patients sampled 7 to 15 times each between 32 and 40 weeks of gestation ranged from 5.3% to 13.6%. Higher serum total estriol concentration correlates with a lower percent of unconjugated. The mean percent unconjugated decreases during the last eight weeks of gestation from 11.4% to 8.4%, with a calculated regression line of Y = 23.323--0.368X. Thus, the concentration of serum unconjugated estriol is relatively more constant. The majority of patients demonstrate a narrow range of percent serum unconjugated estriol. These circumstances, combined with ease of assay, support the use of serum unconjugated estriol in pregnancy estriol monitoring. PMID- 6256549 TI - The distribution of infectious bursal disease in South Africa. AB - From a country-wide serological survey done during 1978 it is evident that the disease is widely distributed in the areas densely populated with poultry in South Africa. This survey was done before vaccine were in general use in the country. PMID- 6256550 TI - Synthesis and biological activity of a ketomethylene analogue of a tripeptide inhibitor of angiotensin converting enzyme. AB - An analogue of a tripeptide inhibitor of angiotensin converting enzyme, Bz-Phe Gly-Pro, has been synthesized in which the amide bond connecting phenylalanine and glycine has been replaced by a ketomethylene group. This nonpeptide analogue, 20, shows more potent converting enzyme inhibiting activity, I50 = 0.07 microM, than Bz-Phe-Gly-Pro, I50 = 9.4 microM, or than the orally active D-3-mercapto-2 methylpropanoyl-L-proline (captopril, 1), I50 = 0.30 microM. Compound 20 has a Ki of 1.06 X 10(-7) and either competitive or noncompetitive enzyme kinetics depending on what substrate is used in the converting enzyme assay. In tests for inhibition of angiotensin I induced contractions in the guinea pig ileum, 20 has one-tenth the activity of 1. PMID- 6256551 TI - Synthesis and biological activities of chloroethylurea, methylurea, and nitrosourea analogues of N-deacetylmethylthiocolchicine. AB - A series of urea and nitrosourea analogues of N-deacetylmethylthiocolchicine (1) has been synthesized, and their antineoplastic and antiviral activities were evaluated. The objective for combination of two active moieties, such as thiocolchicine and nitrosourea, into one molecule was the generation of compounds with potential improved biological and pharmacological properties. The ED50 for 2, 3, 4, and 5 was 1.6, 1.2, 3.3, and 1.8 X 10(-8) M for L1210 cells and 3.0, 2.7, 2.9, and 2.6 X 10(-8) M for S-180 cells, respectively. The synthesis and cytotoxic and antiviral properties of these compounds are discussed. PMID- 6256552 TI - Crystal structures of calcium channel antagonists: 2,6-dimethyl-3,5 dicarbomethoxy-4-[2-nitro-, 3-cyano-, 4-(dimethylamino)-, and 2,3,4,5,6 pentafluorophenyl]-1,4-dihydropyridine. AB - The crystal structures of 2,6-dimethyl-3,5-dicarbomethoxy-4-(2-nitrophenyl)-1,4 dihydropyridine (Nifedipine) and the 3-cyano-, 4-(dimethylamino)- and 2,3,4,5,6 pentafluorophenyl derivatives were determined. The 1,4-dihydropyridine ring in all four compounds has a boat-type conformation with varying degrees of puckering at the C4 position. Increasing distortion from planarity at this position shows a limited correlation with decreasing biological activity, determined as the ability to inhibit the Ca2+-dependent muscarinic-induced mechanical responses of guinea pig ileal longitudinal smooth muscle. PMID- 6256554 TI - Competition for slow channel of Ca2+, Mn2+, Verapamil, and D-600 in rat ventricular muscle? PMID- 6256555 TI - Calcitriol and renal function. PMID- 6256553 TI - Current-voltage analysis of apical sodium transport in toad urinary bladder: effects of inhibitors of transport and metabolism. AB - The basal-lateral surface of the epithelium of the urinary bladder of the toad (Bufo marinus) was depolarized by exposure of the serosal surface to 85 mM KCL and 50 mM sucrose. The extent of depolarization appeared to be virtually complete, as evaluated by the invariance in the transepithelial electrical potential difference and conductance on addition of nystatin (a monovalent cation ionophore) to the serosal medium. The Na-specific current (INa) was defined as the current sensitive to the removal of Na from the mucosal medium or inhibitable by addition of amiloride to this medium. In the presence of the high K-sucrose serosal medium, rapid, serial, stepwise clamping of the transepithelial voltage (V) yielded a curvilinear dependence of INa on V; which is taken to represent the I--V curve of the apical Na channels. The constant field equation (Goldman, D.E. 1943; J. Gen. Physiol. 27:37) fits the I--V data points closely, allowing estimates to be made of the permeability to Na of the apical membrane (PNa) and of the intracellular Na activity (Nac). Exposure of the apical surface to amiloride (5 X 10(-7) M) decreased PNa in proportion to the decrease in INa (i.e., approximately 70%) but decreased Nac only 25%. In contrast, an equivalent reduction in INa elicited by exposure of the basal-lateral surface to ouabain was accompanied by only a 20% decrease in PNa and a sixfold increase in Nac. The effects of amiloride on PNa and ouabain on Nac are consistent with the primary pharmacological actions of these drugs. In addition, PNa appears to be under metabolic control, in that 2-deoxyglucose, a specific inhibitor of glycolysis, decreased INa and PNa proportionately, and lowered Nac marginally, effects indistinguishable from those obtained with amiloride. PMID- 6256557 TI - Studies on the mechanism of "exaggerated natriuresis" in essential hypertension. AB - Prompt and exaggerated natriuresis and diuresis were seen one to two hours after the starting of an infusion of 300 ml of 3% saline for one hour in patients with essential hypertension on a high sodium chloride intake. There were no significant differences in urinary volume and sodium excretion after the saline load in patients with normal and low plasma renin activity. The inhibition of angiotensin converting enzyme with SQ 14225 in patients with normal plasma renin activity did not produce additional natriuresis and diuresis after the saline load. Mean arterial blood pressure and/or changes in mean arterial blood pressure after the saline load showed a positive correlation with urinary volume and sodium excretion in each collection period in hypertensive subjects. Free water reabsorption in hypertensives was lower at high levels of osmolar clearance than that in control subjects. These results suggest that "exaggerated natriuresis" in essential hypertension is due to a decrease in tubular sodium reabsorption, which may be the result of intrarenal hemodynamic changes related to high blood pressure per se. The decreased medullary osmolar gradient is a possible contributing factor in the enhanced sodium and water excretion, while the renin angiotensin-aldosterone system does not seem to play an important role. PMID- 6256556 TI - Evaluation of myocardial infarction by radioisotope myocardial imaging with special reference on thallium-201 myocardial perfusion imaging. AB - One hundred and three patients with myocardial infarctions were studied with 201 thallium chloride and/or 99m-technetium pyrophosphate myocardial imaging and were followed-up for an average of 23 months. There were 24 false negative cases with 201-thallium chloride, but no deaths or serious complications occurred during the follow-up period in these false negative cases. There were six patients with widened QRS complexes (more than 0.12 seconds) without bundle branch blocks and in three of them myocardial infarction was not identified by electrocardiography. However, there were large myocardial perfusion defects in the anterior-inferior wall of the left ventricle. All of this group of patients died suddenly during the follow-up period. The incidence of complications and mortality rose sharply in patients whose myocardial perfusion defects detected by thallium-201 were larger than 40% of the entire left ventricle. The myocardial infarction areas measured by 99m-technetium pyrophosphate were 28.5 +/- 9.8 cm2 in non-survivors and 16.5 +/- 1.7 cm2 in survivors. In addition, ten patients with acute myocardial infarction were studied by double scan methods with thallium-201; myocardial perfusion defect areas were reduced from 29 +/- 3% of the entire left ventricle to 19 +/- 4% by nitrate administration, indicating that there were reversibly ischemic areas in acute myocardial infarction which could be transiently reduced by nitrate. Thus, the study suggests the possibility of decreasing myocardial perfusion defects in the early phase of acute myocardial infarction, leading to a better long term prognosis for the patients. PMID- 6256558 TI - [Effects of neurolept-anesthesia and surgery on plasma anterior pituitary hormone levels in man (author's transl)]. PMID- 6256559 TI - [A case of adult T-cell type lymphoma with generalized cytomegalovirus infection and pneumocystis carinii pneumonia (author's transl)]. PMID- 6256560 TI - [An autopsy case of gastric cancer associated with microangiopathic hemolytic anemia without local relapse after 6 years of gastrectomy (author's transl)]. PMID- 6256561 TI - Complement activating property of the protein-rich endotoxin (OEP) of Pseudomonas aeruginosa. II. Complement activating property of the lipopolysaccharide portion and the inhibition by polymyxin B. AB - In order to elucidate the active principle and the mechanism of complement activation of protein-rich endotoxin (OEP) of P. aeruginosa, the complement consumption of the LPS from OEP was studied either in guinea pig serum (GPS) or in factor D-depleted GPS (D-dpl-GPS) in the presence or absence of polymyxin B. Polymyxin B is an inhibitor of the classical pathway (CP) activation due to the lipid A of LPS. The LPS from OEP had about 5 times higher the activity than OEP in GPS. This value corresponds to the LPS content (about 20%) in OEP. It was not likely that the protein portion (about 80%) of the OEP participates to activate complement. In GPS, the ability of the LPS from OEP was only partially inhibited by polymyxin B. In D-dpl-GPS in which the alternative pathway (AP) may be abrogated, the consumption by the LPS from OEP markedly decreased, and was furthermore diminished in the presence of polymyxin B. These results suggest that the LPS from OEP is the active principle of OEP and activates both the CP and the AP. It was noteworthy that two fold or less polymyxin B in weights did not inhibit the ability of E. coli 0111:B4 LPS to activate only the AP, but rather enhanced it. PMID- 6256562 TI - [Gastric disease and cyclic nucleotides. I. Microassay of cyclic nucleotides in rat stomach (author's transl)]. PMID- 6256563 TI - [The response of plasma cyclic AMP to exogenous glucagon as a marker for severity in acute liver injury (author's transl)]. PMID- 6256564 TI - [A study on pneumoconiosis due to diatomaceous earth dust. (Report 1). Respiratory function abnormalities in workers with and without pneumoconiosis (author's transl)]. PMID- 6256565 TI - [A study on pneumoconiosis due to diatomaceous earth dust. (Report 2). Immunological examinations in workers with and without pneumoconiosis (author's transl)]. PMID- 6256566 TI - [Characteristics of silica gel cold trap for gas sampling (author's transl)]. PMID- 6256567 TI - Effect of ACTH on adrenal estrogens. AB - Tissue levels of rat adrenal estrogens during the estrous cycle were determined by radioimmunoassay, and effect of ACTH on the adrenal estrogen levels was examined. The levels of estrone and estradiol in proestrus were 2.75 +/- 0.61 pg/mg tissue and 1.0 +/- 0.19 pg/mg tissue (mean +/- SE), respectively. The higher level of estrone but not of estradiol was inclined to appear in proestrus rather than in other phases. Injection of 250 IU/kg of alpha 1-24-ACTH significantly increased the estrone level at 15 and 30 min, and estradiol at 15 min. Administration of reserpine, which was used as the ACTH releaser, produced an increase in the estrone level but did not change the estradiol level. While dexamethasone injection decreased the estrone level significantly at 8 hours after the treatment, the level of estradiol remained unchanged. Hypophysectomy produced a considerable decrease in both steroid levels, particularly estrone. These results indicate that the major estrogen in the rat adrenal gland is estrone and that the level is regulated by hypophyseal ACTH. PMID- 6256568 TI - Developmental change of beta-adrenergic receptors in rat brain. AB - The developmental change of beta-adrenergic receptors in rat whole brain, except the cerebellum, was studied by binding assays with (--) 3H-dihydroalprenolol. The synaptic membrane fraction, prepared from 2-day-old and 6-week-old rat brains, had binding sites for (--) 3H-dihydroalprenolol, which seemed to represent physiological beta-adrenoceptors. The maximal binding capacity and the dissociation constant for (--) 3H-dihydroalprenolol of the synaptic membrane fraction did not vary with the age of the rats, but the yield of synaptic membrane fraction from the brain of 2-day-old rats was much less. Therefore, the total number of binding sites was less in 2-day-old rats. In addition, there was a significant difference in the inhibitory effects of 1-isoproterenol on binding of (--) 3H-dihydroalprenolol to the synaptic membrane fractions in the 2-day as compared to the tissues from the 6-week-old animals. The developmental changes in the number and nature of beta-adrenoceptors may result in expression of catecholamine-sensitive adenylate cyclase activity. PMID- 6256569 TI - Na,K-, Mg- and HCO3-adenosine triphosphatases in the rabbit brain choroid plexus. AB - Properties of adenosine triphosphatases (ATPases) in the choroid plexus of rabbit cerebral ventricles were investigated using tissue homogenates and subcellular fractions. Na,K-ATPase or HCO3-ATPase activity of choroid plexus was significantly lower than that of the brain or the kidney, respectively. Among the homogenates of choroid plexus from the lateral, third and fourth ventricles, there were no differences in the activities of Na,K-, Mg- and HCO3-ATPases. In the choroid plexus, Na,K-ATPase activity was demonstrated to be highest in 10,000 X g fraction, while the highest Mg- and HCO3-ATPase activities were observed in 8,000 X g fraction, the so-called mitochondrial fraction. Ion requirement, pH optimum and ouabain sensitivity of Na,K-ATPase in 10,000 X g fraction of choroid plexus were similar to findings in erythrocytes, brain and kidney. However, properties of Mg- and HCO3-ATPases in 8,000 X g fraction were considerably different from those found in the brain and gastric mucosa. In the choroid plexus, thiocyanate ion inhibited Mg-ATPase as well as HCO3-ATPase. These results indicate that characteristics of ATPase systems in the choroid plexus are to some extent different from those in tissues such as brain, kidney and gastric mucosa. PMID- 6256570 TI - Preventive effects of theophylline on anaphylactic shock in rats. AB - Anaphylactic shock was induced by administration of ovalbumin to sensitized rats. Preventive effects of theophylline on anaphylactic shock were examined with regard to the relationship between cyclic AMP and prostaglandin (PG) E2 in lung tissue, and plasma histamine. During anaphylactic shock, levels of cyclic AMP content and PGE2 content in lung tissue decreased, while plasma histamine content increased. Theophylline increased levels of cyclic AMP content and PGE2 content in lung tissue, in a dose dependent manner, and pretreatment of animals with theophylline prevented the onset of anaphylactic shock. Pretreatment with indomethacin abolished the preventive effects of theophylline on anaphylactic shock, and the effect of theophylline on the cyclic AMP content. Dibutyryl cyclic AMP (DBcyclic AMP) increased PGE2 content in lung tissue, in a dose dependent manner, and also prevented the onset of anaphylactic shock. These effects of DBcyclic AMP were inhibited by the pretreatment with indomethacin, and here, cyclic AMP in lung tissue was maintained at a high level. In the group in which anaphylactic shock was prevented with these interventions, PGE2 content in lung tissue was significantly high in all cases. In addition PGE2 infusion prevented anaphylactic shock. These data suggest that theophylline increases cyclic AMP levels in lung tissue only in the presence of endogenous PG, that increased cyclic AMP content in lung tissue subsequently increases PGE2 content in lung tissue, and that the preventive effects of theophylline on anaphylactic shock result from increased PGE2 content in lung tissue. PMID- 6256571 TI - Change in catecholamine-sensitive Na+,K+-ATPase activity in the rat striatum microsomes following electrolytic or 6-hydroxydopamine-induced lesions of dopaminergic neurons. PMID- 6256572 TI - Two-stage carcinogenesis in vitro: transformation of 3-methylcholanthrene initiated Rauscher murine leukemia virus-infected rat embryo cells by diverse tumor promoters. AB - A modified in vitro transformation assay demonstrated potential for use in the identification and study of tumor promoters. Rauscher murine leukemia virus infected F344 rat embryo cells were transformable by various chemical carcinogens when they were administered at appropriate doses. Cells treated with subeffective doses of 3-methylcholanthrene did not transform. However, when these cells were regularly treated with 12-O-tetradecanoylphorbol 13-acetate, sodium phenobarbital, limonene, oleic acid, lauric acid, or saccharin, transformation was observed. Thus several dhemically diverse in vivo tumor promoters behaved as promoters in this in vitro system. This assay appeared to be useful for in vitro efforts to identify promoters and may be of value in studies on the mechanisms of action of these cocarcinogens. PMID- 6256573 TI - Kinetics of responses to tumor antigens and mouse mammary tumor virus in BALB/cCrgl and BALB/cfC3H mice. AB - Spleen cells from BALB/cCrgl mice responded to murine mammary tumor virus (MuMTV) in cell-mediated immune assays at higher levels than did the spleen cells from the syngeneic BALB/cfC3H mice. Implantation in BALB/cCrgl with a chemically induced mammary tumor and in BALB/cfCrgl mice with spontaneous mammary tumors (SMT) arising in the same strain resulted in sensitization of these animals to the antigens of their tumors. Reactivities peaked 3 weeks after transplantation, whereas no positive reactions could be detected when tumors reached maximum size. A kinetic study with the use of MuMTV antigen(s) showed that the responses of lymphocytes from BALB/cfC3H with SMT followed the same pattern as that obtained with tumor antigens, which indicated that this might be a de novo sensitization. In sharp contrast, a steady type of response to MuMTV was observed with the spleen cells from BALB/cCrgl mice; i.e., the levels of responsiveness to MuMTV did not significantly vary at any stage of tumor development. In vivo studies explored the possible relevance of the in vitro cell-mediated immunity to the host defenses. MuMTV-expressing mammary tumor cells were implanted in BALB/cCrgl and BALB/cfC3H mice. The total incidence of tumors was significantly reduced and a delay occurred in their time of appearance in BALB/cCrgl mice in relation to BALB/cfC3H animals. Thus the in vitro reactivity to MuMTV antigen(s) in BALB/cCrgl mice was found to be coincidental with a degree of protection against the development of MuMTV-expressing mammary tumors. PMID- 6256574 TI - A modified enzymatic technique for production of cell suspensions of a murine fibrosarcoma. AB - Collagenase, elastase, and mild mechanical procedures were used to obtain numerous viable single cells in suspension from a murine fibrosarcoma of C57BL/6 origin. This technique produced suspensions with minimal debris. The suspensions were more than 90% viable and yielded over 1.25 x 10(8) cells/g of solid tumor. PMID- 6256575 TI - Infection of feline embryo adherent cells with feline leukemia virus: feline oncornavirus-associated cell membrane antigen expression and morphologic transformation. AB - Feline embryo adherent cells were infected with the Richard or Kawakami-Theilen strains of feline leukemia virus (FeLV) and examined for feline oncornavirus associated cell membrane antigen (FOCMA), viral group-specific antigen (gsa) production, and in vitro evidence of transformation. As early as 10 days after infection, when more than half of the infected cells were gsa positive, FOCMA was detected on 5-10 percent of the cells. Transitory morphologic alterations (epithelioid appearance and rounding) were first noted in most cultures around 20 30 days post infection. At this time, approximately 50% of the cells in infected cultures expressed FOCMA. Morphologic characteristics of transformed fibroblastic cells (rounded shape, disordered alignment, and low adhesion to substratum), as well as enhanced agglutinability by plant lectins and ability to grow in agar, were demonstrated in one of four FeLV-infected, FOCMA-positive cultures. Findings showed that FOCMA may be expressed in FeLV-infected monolayer cells independent of transformation as assessed by in vitro criteria. PMID- 6256576 TI - Development, morphology, and progression of mammary tumors during and after fertile life in BALB/cfRIII mice. AB - A study was done on 368 BALB/cfRIII mammary tumor-bearing breeding female mice that are of the BALB/c genotype and carry milk-transmitted RIII murine mammary tumor virus (MuMTV) infection initiated by foster-nursing. All tumors were characterized by chronologic, biologic, and morphologic analyses. Mammary tumors occurring during pregnancy-lactation periods were mostly pregnancy-dependent plaques showing organoid tubular structure, sudden growth during late pregnancy, regression after delivery, and slow progression. The frequency of pregnancy dependent tumors per 100 mice at risk increased steadily from first (1 tumor) to sixth (38 tumors) pregnancy-lactation period. Mammary tumors occurring after fertile life were mostly characterized by an irregular, slow growth and a type B morphology. The frequency of these tumors per 100 mice at risk per 100 days of survival also increased regularly in females undergoing from one (73 tumors) to six (117 tumors) pregnancy-lactation periods. Data were discussed in the light of the pattern of MuMTV release through BALB/cfRIII milk. PMID- 6256577 TI - Regression of hormone-dependent mammary tumors in Sprague-Dawley rats as a result of tamoxifen or pharmacologic doses of 17 beta-estradiol: cyclic adenosine 3',5' monophosphate-mediated events. AB - The estrogen and cyclic adenosine 3',5'-monophosphate (cAMP)-binding activities changed markedly when 7,12-dimethylbenz[a]anthracene-induced mammary tumors of Sprague-Dawley rats regressed following daily injections of either tamoxifen or pharmacologic doses of 17 beta-estradiol. cAMP binding increased eightfold to tenfold, whereas estrogen binding increased twofold to threefold in regressing tumor nuclei at 5 days after either treatment, which resulted in an inversion of the ratio of estrogen binding to cAMP binding found in growing tumor nuclei. Concomitantly, both binding activities were depleted from the cytosol. In the regressing tumors, the cAMP level increased twofold and nuclear cAMP-dependent protein kinase activity increased threefold to fourfold, with a 70-80% decrease in the cytoplasmic protein kinase activity. The rise in the nuclear protein kinase activity was abolished when cycloheximide was given with tamoxifen or with high doses of 17 beta-estradiol, which suggests that the increased activity is due to new protein synthesis. In the regressing tumor nuclei, the phosphorylation of the regression-associated proteins increased, whereas the phosphorylation of growth-associated proteins decreased. These data suggest that the mammary tumor regression induced by tamoxifen or high doses of estrogen proceed through a series of cAMP-mediated events. PMID- 6256578 TI - An immunohistologic study of Shope fibroma virus in rabbits: tumor rejection by cellular reaction in adults and progressive systemic reticuloendothelial infection in neonates. AB - The development of lesions in adult and neonatal New Zealand White rabbits following intradermal inoculation of Shope fibroma virus was studied by immunofluorescence for viral antigens. T-cells, and immunoglobulin. In adults a self-limiting local fibroxanthosarcomatous tumor was rejected within 10-12 days in association with a dense infiltration of T-cells. In neonates expanding skin lesions were associated with systemic presence of virus in the reticuloendothelial system. In surviving infected neonates, granulomas formed at the site of infection after 3 weeks. These reactions may have limited further dissemination of the virus. These results support the hypothesis that the progressive disease produced by Shope fibroma virus in neonatal rabbits may be due to the inability of the reticuloendothelial system to clear infectious virus. PMID- 6256579 TI - [The effects of topical steroids in epidemic kerato-conjunctivitis (author's transl)]. AB - Fifty-three patients with proven adenovirus type 8 infection were treated at random, in a prospective study, with either artificial tears or topical steroids over six weeks. Severe cases of nummular keratitis, as well as deep keratitis and slight iritis, were significantly less frequent under steroids. No difference existed with respect to the course of the conjunctivitis and the frequency of a superficial punctate keratitis. Furthermore, the overall frequency of nummular keratitis was equal in both groups, its manifestation merely being somewhat delayed in the steroid group. This may even be disadvantageous, as the natural course of the disease could be prolonged. A significant disadvantage of topical steroids, however, was the high incidence of permanent "dry eye" in the post infection period. Therefore, as long as no effective antiviral treatment for adenovirus infection is available, steroids should only be administered to relieve symptoms in severe cases for a limited time. PMID- 6256580 TI - [Polyglycolic acid suture in strabismus surgery (author's transl)]. AB - We report on 60 patients who underwent altogether 100 operations on their eye muscles, either recession or resection of a lateral rectus muscle, or both operations together. All muscles were sutured with 5-0 Dexon, and the conjunctivae with 7-0 Dexon. The postoperative reaction was studied. This suture material produces a good tissue reaction. Tying and knotholding qualities are also good. PMID- 6256581 TI - [Enophthalmos with limitation of bulbar motility as a rare clinical symptom of metastasizing carcinoma of the breast (author's transl)]. AB - A 57-year-old woman presented with a ptosis of her left eye four weeks prior to surgery for scirrhous carcinoma of the breast. Six months later she had blurred vision in her left eye, and double vision occurred three months subsequently. The diagnosis was enophthalmus and ophthalmoplegia. The suspected diagnosis of a distant metastasis of the scirrhous carcinoma of the breast was confirmed by biopsy. The orbital symptoms were a rare first sign not only of a metastatic process, but also of the carcinoma itself. PMID- 6256583 TI - A study of some mitochondrial and peroxisomal enzymes in human colonic adenocarcinoma. AB - Three mitochondrial enzymes, cytochrome oxidase, succinate dehydrogenase, and monoamine oxidase, and two peroxisomal enzymes, catalase and urate oxidase, were measured spectrophotometrically in the postnuclear supernatant prepared from homogenates of normal mucosa and carcinoma of the human colon. The specific activities, in both normal mucosa and carcinoma, varied from patient to patient. However, the difference in these activities between normal mucosa and carcinoma was consistent when patients were compared. The activities of cytochrome oxidase, succinate dehydrogenase, monoamine oxidase, and catalase were greater in normal mucosa than in carcinoma. In contrast, urate oxidase activity increased in carcinoma as compared with normal mucosa. Furthermore, cytochrome oxidase and succinate dehydrogenase decreased proportionally in carcinoma, supporting the concept that the mitochondrial respiration in normal tissue and carcinoma is quantitatively but no qualitatively changed. However, the decrease in monoamine oxidase activity in carcinoma was greater than that observed with other mitochondrial enzyme activities and was irregular. This suggests that a qualitative mitochondrial change may occur in carcinoma. In particular, the ratio between outer membrane enzyme activity and respiratory enzyme activity may be altered. PMID- 6256582 TI - Altered cyclic AMP levels in specific cardiovascular brain centers of spontaneously hypertensive rats (SHR). AB - The possible participation of cAMP in central regulation of arterial blood pressure was investigated in spontaneously hypertensive rats (SHR). Cyclic AMP concentrations of 36 microdissected individual brain areas-including primary and higher cardiovascular centers-were measured in adult SHR and compared with those of normotensive control rats of the same strain and age. In the adult SHR, elevated cAMP concentrations were found in brain areas which are in close connection with the central regulation of blood pressure: nucleus tractus solitarii, A1- and A2- catecholaminergic cell groups in the medulla oblongata, locus coeruleus, central grey matter (subnucleus medialis), and certain cortical areas (especially cingulate cortex and hippocampus). On the other hand, hypothalamic cell groups which have been also suggested to control blood pressure, such as paraventricular, anterior, ventromedial, dorsomedial and posterior hypothalamic nuclei, show lower concentrations of cAMP in the SHR than in normotensive controls. Cyclic AMP levels in 19 other brain areas of SHR which seem to be not involved in mechanisms of central blood pressure regulation practically do not differ from the values of normotensive rats. The results suggest that cAMP-dependent processes are involved in the regulatory mechanisms of central blood pressure control. The brain areas which show alterations of cAMP levels are also distinguished by close neuronal connections to the baroreceptor reflex arc. It is supposed that these areas represent modulatory higher centers capable to affect baroreceptor reflex function. PMID- 6256584 TI - Synthesis of new steroid haptens for radioimmunoassay--VI. 3-O-Carboxymethyl ether derivatives of equine estrogens. Highly specific antisera for measurement of equilin and 17 alpha-dihydroequilin in plasma. PMID- 6256585 TI - Structure-activity relationships for agonistic and antagonistic mineralocorticoids. PMID- 6256586 TI - The Woolf plot is more reliable than the Scatchard plot in analysing data from hormone receptor assays. PMID- 6256587 TI - Effect of prostaglandin E1 and ACTH on proliferation and steroidogenic activity of bovine adreno-cortical cells in primary culture. PMID- 6256588 TI - Juvenile nasopharyngeal angiofibroma. AB - Seven cases of juvenile nasopharyngeal angiofibroma were seen in the Division of Radiation Oncology of the Department of Human Oncology, University of Wisconsin Hospitals from 1961 to 1977. The method of treatments and the end results are discussed. The clinical manifestations and the biological nature of this tumor are analyzed in detail, along with treatment recommendations. PMID- 6256589 TI - A simple microassay for the estimation of renin concentration in plasma. AB - A simple assay for the measurement of renin concentration and renin substrate concentration in microliter quantities of rat plasma is described. In the plasma renin concentration assay 5 microliter of rat plasma was incubated for 2 hr at 37 degrees C in the presence of 20 microliter renin substrate (plasma from nephrectomized rats) and 5 microliter inhibitor-buffer solution pH 7.4. At the end of the enzymic incubation the generated angiotensin I was estimated by radioimmunoassay. Angiotensin I antisera and iodinated angiotensin I were added to the same tube and left to equilibrate at 45 degrees C for 15 hr. EDTA, dimercaprol, and 8-hydroxyquinoline were used to inhibit converting enzymes and angiotensinases. Reproducibility of the assay was good, and recovery of added angiotensin I complete. The normal range of plasma renin in rats was between 7 and 15 pmol angiotensin l/ml/hr. PMID- 6256590 TI - Unpredictable course of small cell undifferentiated lung carcinoma. AB - Twenty-nine patients with small cell lung carcinoma were examined as to ultrastructural morphology, stage of disease, and survival. Although all tumors met the light microscopic criteria for oat cell carcinoma, only 19 (66%) contained neurosecretory granules characteristic of this tumor. Of 12 patients undergoing pulmonary resection, five of six patients with non-neurosecretory tumors and two of six patients with neurosecretory (true oat cell) tumors survived more than 2 years. Survival of all patients with Stage I or II disease was significantly different from that of patients with Stage III disease. Stage together with ultrastructural morphology may carry important therapeutic and prognostic implications. Pulmonary resection appears to be effective treatment for certain subsets of patients with small cell undifferentiated carcinoma. PMID- 6256591 TI - Endocrinology of parturition. PMID- 6256592 TI - Treatment of canine spontaneous diabetes mellitus with aspirin. PMID- 6256593 TI - [Pivmecillinam therapy in acute cystitis--a randomized comparative study of dosages]. PMID- 6256594 TI - [Congenital epulis - report of a case of a so-called granular-cell myoblastoma in a newborn (author's transl)]. AB - We present a case of multiple congenital epulides in a newborn girl. Though the tumors were not excised completely, we found a complete regression after two months. Considering the different clinical characteristics of granular-cell myoblastomas in newborn children and adults we feel, that these lesions may be different entities with similar histomorphological structure. PMID- 6256595 TI - [Classification of the tumours of the minor salivary glands. Pathohistologic analysis of 160 cases (author's transl)]. PMID- 6256596 TI - [The value of the transmandibular approach in cases of extraordinary large tumors (author's transl)]. AB - The problems of diagnostics and surgery of tumors of the retromaxillar space are discussed by means of two characteristic cases. PMID- 6256599 TI - Honored guest's address. PMID- 6256598 TI - Malignant fibrous histiocytoma of the frontal sinus. AB - The first case of malignant fibrous histiocytoma of the frontal sinus is reported. The aggressive nature of the tumor despite its relatively benign histologic pattern and value of electron microscopy are emphasized. Ultrastructural examination reveals a progression of several principal cell types, lending support to the multi-potent mesenchymal cell origin of these malignancies. These cells may have arisen from the supporting stroma of the ectodermally derived respiratory epithelium of the paranasal sinuses. Wide local excision is currently the primary mode of therapy. The value of radiation therapy or chemotherapy in this tumor in unproven. PMID- 6256597 TI - Anti-EBV serologic tests for nasopharyngeal carcinoma. AB - Sixty-three serum specimens from American patients with nasopharyngeal carcinoma were examined for antibodies to antigens associated with Epstein-Barr virus (EBV) and compared with 98 specimens from patients with other head and neck cancers, 133 from patients with benign head and neck diseases, and 96 from healthy donors. The level of antibody titers to EBV-associated antigens was correlated with nasopharyngeal carcinoma. The anti-EBV profile of elevated antibody titers directed against viral capsid antigen and early antigen was seen in undifferentiated and nonkeratinizing tumors but usually not in squamous cell tumors. Titers tended to rise with large increases in total tumor burden caused by distant metastases, often before clinical evidence of metastases. At the time of diagnosis, antibody-dependent cellular cytotoxicity testing was performed on serum samples from 46 of the patients with nasopharyngeal carcinoma. Pretreatment titers were usually low in patients in whom recurrence developed and were high in most of the patients who had a good response to treatment and have remained free of recurrence. PMID- 6256600 TI - [Peripheral nervous system involvement in chronic Chagas disease]. PMID- 6256601 TI - Restriction and modification in B. subtilis: effects on transformation and transfection with native and single-stranded DNA. AB - The effects of restriction in vivo by competent B. subtilis R cells and in vitro by purified endonuclease BsuR on transformation and transfection with native and denatured DNA were investigated. The results show that transformation by either native, or denatured DNA is not affected by restriction, whereas transfection both with native and denatured SPP1 DNA is severely restricted. In contrast to the results obtained in vivo, the biological activity of native and denatured transforming DNA is destroyed by BsuR in vitro, as is the transfecting activity of native and denatured SPP1 DNA. The sensitivity of denatured DNA, either with mixtures of the complementary strands or with separated single strands alone, is significantly lower than that of native DNA. The results are discussed in the context of possible mechanisms underlying the different responses of transforming and transfecting DNA to in vivo restriction by B. subtilis R cells. PMID- 6256602 TI - Restriction and modification in B. subtilis: the role of homology between donor and recipient DNA in transformation and transfection. AB - Non-modified DNAs from phages SPO2 and phi 105, and prophage DNAs extracted from lysogens carrying these phages, were used to transfect isogenic r+m+ B. subtilis recipients which were either non-lysogenic, or had been lysogenized with a homologous or a non-homologous phage. Restriction of transfecting phage and prophage DNA occurred in non-lysogenic recipients and in recipients lysogenic for a non-homologous phage. No effect of restriction was observed when phage or prophage DNA was used to transfect recipients carrying a homologous prophage. This is analogous to the absence of restriction in transformation and indicates that in B. subtilis the distinction between transforming and transforming and transfecting DNA is not made at the initial stages of DNA uptake and processing, but rather at later stages, where recognition of homologous regions in donor and recipient DNA plays an important role. PMID- 6256603 TI - A cloned suppressor tRNA gene relaxes stringent control. PMID- 6256604 TI - Cloned structural gene (ompA) for an integral outer membrane protein of Escherichia coli K-12: localization on hybrid plasmid pTU100 and expression of a fragment of the gene. PMID- 6256605 TI - Localization of mucidin-resistant locus muc3 on mitochondrial DNA with respect to ubiquinol-cytochrome c reductase deficient box loci. Locus muc3 is allelic to box2. AB - Genetic relations between mitochondrial mucidin-resistant locus muc3 and ubiquinol-cytochrome c reductase-deficient box loci have been studied by recombination and petite deletion analysis. It was found that the locus muc3 maps in the segment of mitochondrial DNA corresponding to the locus box2. The results suggest the participation of box2/muc3 locus in the sequences of the structural gene for cytochrome b. PMID- 6256606 TI - Genetic organization and restriction enzyme cleavage map of the ksgA-pdxA region of the Escherichia coli chromosome. AB - Small multicopy plasmids carrying the Escherichia coli genes ksgA and pdxA were constructed by ligation in vitro of an EcoRI restriction fragment from lambda ksg10 (Andresson and Davies, 1980a) into the EcoRI sites of the ColE1 plasmids RSF2124 and pVH51. Cleavage maps of the plasmids were determined for 21 different restriction enzymes. The ksgA gene was located in a 750 basepairs (bp) region 1,450 bp clockwise of the EcoRI site in folA: pdxA is in a 2,040 bp region immediately clockwise of ksgA. PMID- 6256608 TI - The ral gene of phage lambda. II. Isolation and characterization of ral deficient mutants. AB - The lambda ral function modulates the restriction and modification activities of the Escherichia coli K12 and B restriction enzymes (Zabeau et al., 1980). In order to further analyse this function, ral deficient mutants have been isolated, using a method which exploits the property of the strong mutagen N-methyl-N' nitro-N-nitrosoguanidine (N.G.) to induce multiple closely linked mutations. Hence, mutagenized phages carrying mutations in one locus were frequently found to contain additional mutations in adjacent loci. This very efficient mutagenesis procedure enabled us to isolate 27 independent Ral deficient mutants. Seven mutants were found to affect the ral gene directly and were located between the genes N anc cIII. Detailed mapping of two of these mutants showed that the lambda ral gene is located at position 70.6-70.9% on the physical map. The isolation and characterization of these mutants further supports the conclusion that ral is a gene different from the N gene, and demonstrates that the ral gene product is responsible for both counteracting restriction and enhancing modification. PMID- 6256607 TI - The ral gene of phage lambda. I. Identification of a non-essential gene that modulates restriction and modification in E. coli. AB - Host controlled restriction in Escherichia coli can be relieved by pre-infecting restricting cells with modified lambda helper phages. This process, in which intact unmodified phage genomes are allowed to escape restriction attack, is mediated by a newly identified lambda function called ral. The ral gene has been located by deletion mapping between cIII and N. Efficient expression of the ral gene requires the product of the regulator gene N. Polyacrylamide gel analysis of the lambda proteins specified by the cIII-N region failed to reveal the product of the ral gene, but demonstrated that protein Ea10 is encoded by a gene located immediately to the left of ral. From these results the map order cIII-Ea10-ral TL1-N was deduced. Ral specifically alleviates restriction in E. coli K and E. coli B, but does not affect restriction systems EcoRI, EcoRII and EcoP1. In addition, ral enhances the modification activity of the EcoK and EcoB restriction enzymes: we observed that efficient modification of progeny phages obtained by propagating unmodified lambda phages in r-m+ hosts, is dependent upon the presence of ral. We thus conclude that the ral gene product acts by modulating the restriction and modification activities of the type I restriction systems in E. coli, and the possible mechanisms will be discussed. PMID- 6256610 TI - Effects of hyperbaric oxygen on the growth and properties of Pseudomonas aeruginosa. AB - Growth of Pseudomonas aeruginosa in 2 atmospheres absolute of 100% oxygen at 37 degrees C produced two types of abnormal colonies--stunted, rough colonies, termed dwarfs, and large, domed, mucoid colonies, termed giants. The occurrence of these variants depended upon the partial pressure of oxygen and the inoculum size. Subculture of dwarf or giant colonies produced a mixture of both colony types after incubation in hyperbaric oxygen, and colonies of normal appearance after incubation in air. Electron micrographs of ultrathin sections showed that cells from dwarf colonies had a more clearly defined envelope region than cells from normal colonies. Giant colony and normal colony-derived cells were of similar appearance. Whole cells from giant colonies contained more carbohydrate, readily extractable lipid, neutral lipid and free fatty acid than cells from normal colonies; the two cell types showed similar contents of 2-keto,3 deoxyoctonic acid and total phospholipid, but different proportions of individual phospholipids. Cells from dwarf, giant and normal (air-grown) colonies were incubated in air on nutrient agar containing either polymyxin, tetracycline or phenoxyethanol. Relative to cells from normal colonies, cells from dwarf colonies showed enhanced resistance to all three agents and cells from giant colonies showed enhanced resistance to polymyxin and tetracycline only. The resistance of cells from variant colonies was lost following a single subculture in air in the absence of antibacterial agents. It was concluded that the envelopes of cells from dwarf and giant colonies differed both from each other and from those of normal cells. These differences, and the formation of variant colonies, appeared to result from bacterial adaptation to hyperbaric oxygen rather than from mutation. PMID- 6256609 TI - The ral gene of phage lambda. III. Interference with E. coli ATP dependent functions. AB - The ral gene of phage lambda has previously been shown to counteract host controlled restriction and to enhance DNA modification in Escherichia coli (Zabeau et al., 1980). The studies presented in this paper demonstrate that although ral plays only a minor role in the lytic development of phage lambda, it counteracts different E. coli functions, which, like the E. coli restriction system, are ATP dependent. First, ral was found to specifically decrease the efficiency of recombination mediated by the RecBC pathway. Secondly, we observed that E. coli strains in which ral is constitutively expressed, exhibit phenotypes analogous to those of strains carrying mutations in the transcription termination factor rho. In addition, in rho deficient strains general recombination and host controlled restriction are both reduced. These findings strongly suggest that ral might be a second anti-termination function, which in contrast to the lambda N gene product directly antagonizes rho. PMID- 6256611 TI - [A study on the prevalence of cytomegalovirus complement-fixing antibodies in the Turkish population (author's transl)]. AB - The prevalence of cytomegalovirus (Ad 169) antibodies in the Turkish population is studied by complement fixation techniques in 692 sera obtained from various age groups. The titer of 1:8 or higher antibody levels detected in 68% of 0-5 age groups and in 93% of 55 and above ages. Our findings proved that cytomegalovirus infections are frequent and recurrent in Turkish community like other countries which have low living and socio-economical standards. PMID- 6256612 TI - Fibrinolytic and antithrombotic action of bromelain may eliminate thrombosis in heart patients. AB - It has been established that a bromelain plasminogen activator will produce plasmin in rat experiments. In addition the plasmin cleaves Hageman factor in a way that leads to a strong release of kallikrein but a weak release of thrombin. A possible mechanism is suggested to explain how the body can maintain thrombin at a level too low to cause platelet aggregation but adequate to stimulate release of prostaglandins and enzymes for more than 24 hours from a single dose of the pineapple enzymes. Since bromelain therapy leads to formation of platelets with increased resistance to aggregation, it is obvious that the dominant endogenous prostaglandins being produced must be from the group that increases platelet cyclicAMP levels (prostacyclin, PGE1, etc.). The combination of fibrinolytic and antithrombic properties appear to be effective and two large scale tests on heart patients have shown a practically complete elimination of thrombosis. PMID- 6256613 TI - Is type 1b glycogenosis related to an anomeric preference for glucose-6-phosphate uptake by hepatic microsomes? AB - The contradictory data obtained in studies of type 1b glycogenosis would be explained by an anomeric preference for the capture of glucose-6-phosphate by hepatic microsomes. The alpha anomers of hexoses would be utilized preferentially by glycogenolysis and gluconeogenesis, while the beta anomers of hexoses would be preferentially utilized for glycolysis. PMID- 6256614 TI - Neuropeptide modulation of opiate and ethanol tolerance and dependence. AB - Evidence exists to suggest that there are neurochemical responses common to the development of tolerance to and dependence on a variety of psychoactive drugs. Experimental data indicates that pituitary peptides such as corticotropin and vasopressin, in addition to the endorphins, influence the development of physical dependence on either morphine or ethanol. If these findings are supported by further investigations with human subjects, various manipulations of pituitary adrenal function, such as the administration of corticotropin and vasopressin analogs or drugs such as dexamethasone, may prove to be of clinical utility. PMID- 6256616 TI - [Isocyanate pathology: immunological diagnostic methods (author's transl)]. PMID- 6256615 TI - [Update on the neurotoxicity of n-hexane]. PMID- 6256618 TI - Hypoglycemia in a child with hepatoblastoma. AB - A five-year-old boy with hepatoblastoma, who showed a severe hypoglycemia as an initial symptom, was studied. After resection of tumors, hypoglycemia disappeared and did not recur despite recurrence of tumor. A high concentration of insulin like activity (ILA) was found in preoperative serum and in the tumor extract. Hypoglycemia in this patient seemed to depend mainly on ILA and in part on liver enzyme activities related to carbohydrate metabolism. PMID- 6256617 TI - The effect of lithium chloride on the replication of herpes simplex virus. AB - Lithium chloride inhibited the replication of type 1 and type 2 Herpes simplex virus at concentrations which permitted host cell replication. Virus polypeptide and antigen synthesis were unaffected while viral DNA synthesis was inhibited. The replication of two other DNA viruses, pseudorabies and vaccinia virus, was inhibited but there was no inhibition of two RNA viruses, namely, EMC and influenze virus. PMID- 6256619 TI - [The role of the respiratory syncytial (RS) virus in bronchiolitis. Clinico epidemiological and virological study of 33 cases hospitalized in the period February-April 1979]. PMID- 6256620 TI - [Vegetable fiber in child nutrition]. PMID- 6256622 TI - [Urethro-adnexitis]. AB - Urethroadnexitis in the male is one of the most frequent diseases with which the urologist has to deal and, because of the complex anatomical and physiological connections as well as the polymicrobial genesis, to which he must devote particular care in diagnosis in order to be able to carry out rational treatment. To avoid unnecessary antimicrobial therapy, congestive states and psychovegetative complaints must be differentiated. The pathophysiology, diagnosis and therapy of the acute and chronic forms are discussed. PMID- 6256623 TI - Metabolic epidemiology of large bowel cancer. Fecal mutagens in high- and low risk population for colon cancer. A preliminary report. AB - Because of potential significance of fecal mutagens in the pathogenesis of colon cancer, the dietary pattern and fecal mutagens of 3 populations with distinct risk for the development of colon cancer, a high-risk population in New York Metropolitan area (non-Seventh-Day Adventists), a low-risk population of vegetarian Seventh-Day Adventists in New York Metropolitan area and a low-risk population in rural Kuopio, Finland were studied. The average daily intake of protein was the same in the 3 groups, but the sources were different, a greater portion coming from meat in the New York non-Seventh-Day Adventists and from vegetables in Seventh-Day Adventists. The intake of fat was lower in Seventh-Day Adventists and higher in Kuopio and in New York non-Seventh-Day Adventists. The intake of dietary fiber was high in Kuopio compared to other groups. Fecal samples collected for 2 days were freeze-dried extracted with peroxide-free diethyl ether, partially purified on a silica-gel column and assayed for mutagenicity using the Salmonella/mammalian microsome mutagenicity test. The mutagenic activity was observed with Salmonella typhimurium tester strain TA98 without microsomal activation and with TA100 with and without microsomal activation in high-risk subjects from New York consuming a high-fat, high-meat diet. The incidence of fecal mutagen activity was higher in volunteers from New York consuming a high-fat, high-meat diet compared to low-risk rural Kuopio population. None of the vegetarian Seventh-Day Adventists showed any mutagenic activity. PMID- 6256624 TI - A clinicopathologic study of acrodystrophic neuropathies. AB - Sixteen patients presenting with trophic changes associated with a peripheral neuropathy were investigated. Muscle power was normal in all patients, but neurogenic muscle atrophy was demonstrated in 4 of the 7 patients who had a muscle biopsy. Alcoholism was responsible for the neuropathy in 11 patients. In the other patients, one had primary hemochromatosis without diabetes and another a dominantly inherited primary hypertrophic neuropathy. Qualitative and quantitative light and electron microscopic studies, including teased nerve fiber preparations, showed axonal loss as the most salient feature. In the alcoholic patients, the large myelinated fibers were primarily involved, followed by small myelinated and unmyelinated fibers. The lesions were predominant distally as shown in patients who had a sural nerve biopsy at both calf and ankle levels. A mechanism of dying-back degeneration of the longest sensory fibers is the most plausible explanation for neurological and pathological abnormalities. In alcoholic neuropathy with trophic changes, loss of sensory fibers is more important than in alcoholic neuropathy without trophic changes. In familial and sporadic cases, axonal loss is more severe and unmyelinated fibers are more severely affected than in alcoholic acrodystrophic neuropathy. Patients with peripheral neuropathies who present with loss of pain sensation but have preserved muscle power are especially exposed to the development of trophic changes induced by usual trauma in insensitive tissues. PMID- 6256621 TI - The tumor antigens and the early functions of polyoma virus. PMID- 6256625 TI - The pathology of peripheral nerve. PMID- 6256626 TI - Sudden myelopathy secondary to therapeutic total-body hyperthermia after spinal cord irradiation. PMID- 6256627 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 10-1981. PMID- 6256628 TI - Viral gastroenteritis. PMID- 6256629 TI - More on captopril and measurement of angiotensin-converting enzyme. PMID- 6256630 TI - Placental transfer of hepatitis A antibody. PMID- 6256631 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 8-1981. PMID- 6256632 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 9-1981. PMID- 6256633 TI - Emerging concepts concerning drug abuse. PMID- 6256634 TI - Somatosensory affectional deprivation (SAD) theory of drug and alcohol use. PMID- 6256635 TI - Opiate receptors and their implications for drug addiction. PMID- 6256636 TI - Modes of genome evolution. PMID- 6256637 TI - Moloney murine sarcoma proviral DNA is a transcriptional unit. AB - A portion of Moloney murine sarcoma virus DNA which is repeated at both ends of the provirus has been sequences. The nucleotide sequence, together with hybridization data obtained with in vitro pulse-labelled nascent viral RNA, indicate that initiation and termination of RNA synthesis occur within that region of the proviral DNA. A model for transcriptional readthrough of termination signals during RNA synthesis in this system is suggested. PMID- 6256638 TI - Differential regulation of the alpha 2-adrenergic receptor by Na+ and guanine nucleotides. AB - Many hormones interact with receptors which stimulate the enzyme adenylate cyclase. Less well characterized ar those receptors which mediate an inhibition of adenylate cyclase activity. However, guanine nucleotides are clearly important in the regulation of both stimulatory and inhibitory receptors. Monovalent cations, notably Na+, regulate many inhibitory receptor systems but apparently not stimulatory receptors. We investigate here the effects of Na+ and guanine nucleotides on the adenylate cyclase-coupled inhibitory alpha 2-adrenergic receptor of the rabbit platelet. Computer modelling of adrenaline competition curves with 3H-dihydroergocryptine (3H-DHE) indicates that adrenaline induces two distinct affinity states of the alpha 2 receptor--one of higher (alpha 2H) and the other of lower (alpha 2L) affinity. Guanyl-5'-yl-imidodiphosphate (Gpp(NH)p) seems to reduce adrenaline affinity to converting the high-affinity state into the low-affinity form of the receptor. In contrast, Na+ reduces adrenaline affinity at both the high- and low-affinity states of the alpha 2 receptor while preserving receptor heterogeneity. Thus, guanine nucleotides and Na+ differ in the manner by which each reduces agonist affinity for the alpha 2-adrenergic receptor. PMID- 6256639 TI - Receptor binding and internalization of immobilized transcobalamin II by mouse leukaemia cells. AB - Membrane transport of vitamin B12 (cyanocobalamin; Cbl) into mammalian cells is mediated by the serum protein transcobalamin II (TCII). In mouse leukaemia L1210 cells, TCII-Cbl binds to membrane receptors in a rapid, temperature-independent step and is internalized by a slow, temperature-dependent process. To delineate the location of receptors on these cells, we have constructed a visual probe by covalently coupling purified TCII-Cbl to submicrometre latex particles (minibeads). We report here that when L1210 cells are incubated with minibeads containing TCII-Cbl at 4 degrees C and examined by scanning electron microscopy (SEM), the particles are found attached predominantly to microvilli. Incubation of the cells at 37 degrees C results in the internalization of the minibeads. As visualized by transmission electron microscopy (TEM), this endocytotic process seems to occur in clathrin-coated pits and vesicles at the cell surface. PMID- 6256640 TI - Identification of the BAL-labile factor. AB - One of us has previously reported that treatment of the Keilin and Hartree heart muscle preparation with 2,3-dimercaptopropanol (BAL), in the presence of air, leads to the complete inactivation of the succinate oxidase system with little if any effect on the activities of succinate dehydrogenase (until more than half the BAL was oxidized) or cytochrome c oxidase. The inactivation of the complete succinate oxidase system requires the oxidation of BAL by air in the presence of the enzyme. It is not caused by H2O2 or BAL disulphides produced during the oxidation of BAL. Spectroscopic studies identified the block as lying between cytochromes b and c. It was suggested that a BAL-labile factor is present which transfers electrons from cytochrome b to cytochrome c and which is destroyed by coupled oxidation with BAL. The factor is also required for NADH oxidation. Subsequent work showed it is not identical with cytochrome c1 (ref. 4), myoglobin present in the preparation or the antimycin-binding site. We report here that this factor is identical to the iron-sulphur protein in the central portion of the respiratory chain first identified by Rieske. PMID- 6256641 TI - Role of src gene in growth regulation of Rous sarcoma virus-infected chicken embryo fibroblasts. AB - We report here a study of the mechanisms leading to loss of growth control in chicken embryo fibroblasts transformed by Rous sarcoma virus (RSV). We have been particularly concerned with the role of the src gene in this process, and have used RSV mutants temperature sensitive (ts) for transformation to investigate the nature of the growth regulatory lesion. The two principal findings were (1) the stationary phase of the cell cycle (G1) in chick embryo fibroblasts seems to have two distinct regulatory compartments (using the terminology of Brooks et al. we refer to these as 'Q' and 'A' states). When rendered stationary at 41.5 degrees C by serum deprivation, normal cells enter a Q state, but cells infected with the ts-mutant occupy an A state. (2) Whereas normal cells can occupy either state depending on culture conditions, the ts-infected cells, at 41.5 degrees C, do not seem to enter Q even though a known src gene product, a kinase, is reported to be inactive at this temperature. We discuss the possibility that viral factors other than the active src protein kinase influence growth control in infected cultures. PMID- 6256642 TI - An embryo protein induced by SV40 virus transformation of mouse cells. AB - A specific protein of molecular weight (MW) approximately 55,000 (55K) was found recently by immunoprecipitation in all SV40 virus-transformed mammalian cells, in addition to the SV40 large T antigen (appoximately 94K) and small antigen (approximately 17K), which are the only proteins coded by the 'early half' of the SV40 genome. The 55K protein is encoded by cellular DNA; its peptide pattern is different from that of the SV40 antigens and it is species specific in mouse, rat, hamster, monkey and human SV40-transformed (or infected) cells. A 55K protein with a similar peptide pattern was found in mouse embryonal carcinoma cells not exposed to SV40. Similar proteins were reported in mouse sarcomas and leukaemias induced by a great variety of aetiological agents and also in a spontaneously transformed mouse fibroblast cell line, and it has been suggested that the protein may be a general correlated of cellular tumorigenicity. We now report that the approximately 55K protein is present in primary cell cultures from 12-14 day old mouse embryos, but not in 16-day old mouse embryos. The embryo protein has a peptide pattern virtually indistinguishable from that of the SV40 induced protein. We also show by comparing closely related cell families that spontaneously transformed highly tumorigenic mouse cells do not possess the 55K protein. PMID- 6256644 TI - Superoxide involvement in negative air ion effects. PMID- 6256643 TI - Defective repair of alkylated DNA by human tumour and SV40-transformed human cell strains. AB - We have identified a group of 8 (among 39) human tumour cell strains deficient in the ability to support the growth of adenovirus 5 preparations treated with N methyl-N'-nitro-N-nitrosoguanidine (MNNG), but able to support the growth of non treated adenovirus normally. This deficient behaviour defines the Mer- phenotype. Strains having the Mer- phenotype were found to arise from tumours originating in four different organs. Relative to Mer+ strains, Mer- tumour strains showed greater sensitivity to MNNG-produced killing, greater MNNG-stimulated "DNA repair synthesis and a more rapid MNNG-produced decrease in semi-conservative DNA synthesis. Here we report that (1) Mer- strains are deficient in removing O6 methylguanine (O6-MeG) from their DNA after [Me-14C]MMNG treatment (Table 1); (2) Mer- tumour strains originate from tumours arising in patients having Mer+ normal fibroblasts (Fig. 1a, b); (3) SV40 transformation of (Mer+) human fibroblasts often converts them to Mer- strains (Fig. 1c, d); (4) MNNG produces more sister chromatid exchanges (SCEs) in Mer- than in Mer+ cell strains (Fig. 2). PMID- 6256645 TI - Did retroviruses evolve from transposable elements? PMID- 6256646 TI - Isolation of a gene from Drosophila by complementation in yeast. AB - Transformation of mutant yeast cells by cloned genomic DNA from a higher eukaryote has made it possible to isolate a Drosophila DNA sequence that complements a yeast adenine-8-mutation. A 0.8-kilobase poly(A)-containing RNA is transcribed from the cloned Drosophila segment in transformed yeast cells and can account for functional expression of the gene. PMID- 6256647 TI - Synaptic localization of kainic acid binding sites. AB - The heterocyclic compound kainic acid (KA) is a potent excitant when applied to mammalian neurones. Lesions caused by injections of KA into the rat striatum and hippocampus cause similar patterns of damage to those seen in Huntington's chorea and status epilepticus, respectively. Although it was originally thought to be a glutamate agonist, it is now clear that KA does not act on the majority of the receptors for glutamate, and in fact seems to act on a class of receptors which are distinct from those which mediate responses to other excitatory amino acids. The potent and selective neurotoxic effects of this compound may be mediated by these same receptors. At present, the relative distribution of junctional and extrajunctional (non-synaptic) receptors is unknown and resolution of this issue would provide important insights into the action of KA on the central nervous system (CNS). We show here that KA binding sites are greatly enriched in isolated synaptic junctions from rat brain and, using an in vitro autoradiographic technique, we have found that these binding sites are concentrated specifically in terminal fields where KA acts as a potent neurotoxin. PMID- 6256648 TI - Corticotropin regulates transsynaptically the activity of septo-hippocampal cholinergic neurones. AB - The activity of septo-hippocampal neurones is affected by the action on cholinergic perikarya in the septum of a variety of putative neurotransmitters, including substance P and beta-endorphin. (The latter is released in the septal region from neurones which originate in the medial basal hypothalamus.) It has also been reported that two other neuropeptides, corticotropin (ACTH1-24) and alpha-melanotropin (alpha-MSH), affect acetylcholine turnover in septo hippocampal neurones in a manner that is not blocked by transection of the afferents to the hippocampus, from which it has been inferred that the neurotransmitters act directly on the hippocampus. We now describe experiments with corticotropin which show that the effect is rather the influence on septo hippocampal cholinergic neurones of peptidergic neurones within the septum. PMID- 6256649 TI - Defect in cyclic AMP phosphodiesterase due to the dunce mutation of learning in Drosophila melanogaster. AB - Cyclic AMP is an intracellular mediator ('second messenger') in the nervous and endocrine control of cellular function, regulating different processes in different cell types. Although evidence is incomplete, it seems that cyclic AMP enhances the calcium-mediated release of neurotransmitter in some neurones. A simple form of memory in the mollusc Aplysia is probably encoded as a cyclic AMP induced enhancement of neurotransmission at certain synapses of the central nervous system. The possibility that cyclic AMP participates in learning mechanisms may be explored using genetic mutants. For this purpose the fruitfly Drosophila is suitable as it is genetically well characterized and can learn through olfaction, vision or taste. We show here that independent searches for mutations of olfactory learning and of cyclic AMP metabolism, and for mutations causing female infertility have each led to the same gene--the dunce gene. Our evidence indicates that the normal dunce gene may specify a cyclic AMP phosphodiesterase. PMID- 6256650 TI - Altered substrate specificity of herpes simplex virus thymidine kinase confers acyclovir-resistance. AB - Acyclovir (9-[2-hydroxyethoxymethyl]guanine or ACV) is a nucleoside analogue with considerable potential for the treatment of herpes simplex virus (HSV) infections in man. Two virus-coded enzymes are important in the mechanism of action of this drug: thymidine kinase (TK) which initiates its activation by converting it to the monophosphate and DNA polymerase whose action is inhibited by ACV triphosphate. Changes in either gene may confer resistance, but all reported mutations in the TK gene have resulted in failure of the resistant virus to induce appreciable levels of the enzyme. Such TK- mutants arise readily in tissue culture systems where the enzyme is non-essential for virus replication, but in animals they show considerably reduced pathogenicity and neurovirulence. We now describe the isolation of a resistant mutant which induces a TK of altered substrate specificity and we show that this virus retains pathogenicity for mice with only a slight attenuation of neurovirulence. PMID- 6256651 TI - Terminal direct repeats in a retrovirus-like repeated mouse gene family. AB - The mouse genome contains multiple copies of a dispersed gene family known individually as VL30 genes which are thought to be associated with retroviruses. The copies consist of closely related 5.2-kilobase DNA sequences flanked by unrelated cellular DNA, and although no sequence homology has been found between the genes and the exogenous or endogenous retroviruses so far tested, the 30S RNA transcripts expressed by the genes are efficiently packaged into virions, recovered from infected cells and transmitted to other cells by pseudo-type infection. Stimulated by recent reports of the similarity between retroviruses and transposons (from which retroviruses may have evolved), and in particular by the recognition that both types of genetic elements are characterized by a large terminal repeat (LTR), we set out to determine whether the VL30 genes are also distinguished by this property. Using cloned DNAs from a mouse gene library and heteroduplex analysis, we have now found that the VL30 genes do indeed carry terminal direct repeats 400 base pairs long. PMID- 6256652 TI - A general method for site-directed mutagenesis in prokaryotes. AB - The genetic analysis of genes from prokaryotic species for which experimental genetic systems have not yet been developed is often limited by the difficulty of producing mutations in those genes. We report here a general technique applicable to Gram-negative prokaryotes for site-directed mutagenesis of cloned DNA fragments which we have applied to the study of the symbiotic nitrogen fixation genes of Rhizobium meliloti. In particular, we mutagenized cloned R. meliloti restriction fragments in Escherichia coli with transposon Tn5 and then replaced the wild-type parental DNA sequences with the mutant DNA sequences in the R. meliloti genome. Using this method we show that an R. meliloti DNA restriction fragment, cloned previously on the basis of homology to Klebsiella pneumoniae nif genes, contains gene(s) essential for symbiotic nitrogen fixation. In addition, we use this method to construct a physical genetic map of a subset of the R. meliloti nif genes. PMID- 6256653 TI - Persistent parainfluenza virus shedding during isolation at the South Pole. AB - Persistent parainfluenza virus shedding in healthy young adults occurred throughout the 8 1/2-month winter isolation period at Amundsen-Scott South Pole Station during 1978. Two episodes of respiratory illness were observed after 10 and 29 weeks of complete social isolation. Throat swabs collected both routinely, and during each outbreak of respiratory illness, were directly inoculated into cell cultures. Parainfluenza virus types 1 and 3 were recovered from both symptomatic and asymptomatic subjects throughout the winter. No other viruses were obtained by these efforts. The presence of parainfluenza virus in these subjects long after the accepted incubation period for viral upper respiratory illness, and when the introduction of new virus to this community was impossible, suggests its persistence in man. PMID- 6256654 TI - Theory agrees with experimental thermal denaturation of short DNA restriction fragments. AB - Experimental melting transitions of several natural DNAs of known nucleotide sequences have recently been obtained. The differential melting curves of these DNAs-phi X174 DNA, fd DNA and SV40 DNA-all show distinctive sets of peaks or fine structure. Theoretical melting curves calculated from the sequences and a few a priori parameters have not accurately predicted the experimental transitions. Although calculated fine structure resembled experimental curves in some cases, the characteristic features of a DNA's differential melting curve could not generally be produced. Azbel and Gabbarro-Arpa et al. have recently obtained good agreement between calculated and experimental curves using a different theoretical approach-only ground-state configurations of DNA were considered for temperatures inside the transition region. Their results suggest that the basic model of DNA melting, common to all theoretical approaches, is accurate. We have used here an exact theoretical approach to calculated melting curves of four DNA restriction fragments of 95-301 base pairs containing the lactose promoter region (Fig. 1). Theoretical curves agree very well with the experimental transitions published by Hardies et al. and obtained in this laboratory. PMID- 6256655 TI - Regulation of transcription in expressed and unexpressed mating type cassettes of yeast. AB - The genes that control the a, alpha and a/alpha cell types in Saccharomyces are carried on transposable elements known as a and alpha cassettes which reside at three different chromosomal loci. Examination of the transcripts by R-looping and filter hybridization indicates that each cassette is capable of producing two divergent transcripts. Cassettes at the MAT locus are transcribed constitutively. Transcription of cassettes at HML and HMR is prevented by trans-acting negative regulators. PMID- 6256656 TI - A position effect in the control of transcription at yeast mating type loci. AB - The two mating type loci MATa and MAT alpha each produce two mRNAs that are transcribed in opposite and diverging directions from central promoters. Silent copies of MATa (HMRa) and MAT alpha (HML alpha) contain identical DNA sequences throughout the transcribed region, yet are not transcribed. It is concluded that sequences to the left of HMRa (and probably HML alpha) must somehow affect transcription initiated at the centre of each locus 700 to 1,400 base pairs away. A possible mechanism for this position effect is discussed. PMID- 6256657 TI - Homology and non-homology at the yeast mating type locus. AB - Four mutations of the alpha mating type locus of Saccharomyces cerevisiae have been analysed to determine their relationship to the a mating type locus. Mat alpha+ recombinations are produced by mat alpha 2-/MAT but not by mat alpha 1 /MATa diploids. MAT alpha and MATa thus contain regions of homology (coding for at least part of MAT alpha 2) and regions of non-homology (coding for at least part of MAT alpha 1)-the genetic determinant for cell type is larger than the non homologous sequence seen by DNA-DNA heteroduplexes and genetic analysis. The segment transposed in mating type interconversion includes both types of sequence. PMID- 6256658 TI - Nucleotide sequences at host-proviral junctions for mouse mammary tumour virus. AB - Proviruses cloned from rat cells infected with mouse mammary tumour virus, a B type retrovirus regulated by glucocorticoid hormones, show the structural features of transposable elements: short inverted repeats conclude long direct repeats at the ends of viral DNA, and short sequences of cellular DNA are duplicated during integration and flank each provirus. The integrative mechanism joins a precise site in viral DNA to non-homologous sites in host DNA. PMID- 6256659 TI - Nucleotide sequence and formation of the transforming gene of a mouse sarcoma virus. AB - The complete nucleotide sequence of the transforming gene of a mouse sarcoma virus has been determined. It codes for a protein of 374 amino acids. The nucleotide sequence of the junctions between a murine leukaemia virus and cellular sequences leading to the formation of the viral transforming gene have also been elucidated. The viral transforming sequence and its cellular homologue share an uninterrupted stretch of 1,159 nucleotides, with few base substitutions. The predicted amino acid sequence of the mouse sarcoma virus transforming gene was found to share considerable homology with the proposed amino acid sequence of the avian sarcoma virus oncogene (src) product. PMID- 6256660 TI - Cyclosporin A promotes spontaneous outgrowth in vitro of Epstein-Barr virus induced B-cell lines. AB - Cyclosporin A (CSA) is a fungal metabolite which exerts profound effects on the immune system and has potential as a selective immuno-suppressive agent. Clinical trials with human renal allograft recipients have confirmed this potential but there have been disturbing reports of lymphoma in a significant number of patients. Despite extensive animal studies, the specificity of this drug for human lymphocyte subpopulations is largely unknown. We demonstrate here that in vitro CSA has no apparent effect on Epstein-Barr virus (EBV)-induced B-lymphocyte activation, but totally inhibits the T-cell dependent pokeweed mitogen (PWM) B cell response. In addition, CSA markedly facilitates the outgrowth of B lymphoblastoid cell lines from both EBV-infected and non-infected lymphocytes of EBV immune donors cultured in vitro. These results indicate that CSA can interfere with the lymphocytes normally responsible for maintaining the life-long carrier state initiated by primary infection with EBV, allowing outgrowth of the persistently infected cells circulating in the peripheral blood. PMID- 6256661 TI - Nonenzymatic hydroxylations of proline and lysine by reduced oxygen derivatives. AB - The biosynthesis of trans-3- and trans-4-hydroxyprolines and 5-hydroxylysine in animal cells requires polypeptide proline or lysine, enzymes and cofactors including iron, and possibly involves peroxidatic intermediates. Several laboratories have reported the presence of low-molecular-weight hydroxyproline and hydroxylysine peptides in cell and organ cultures. We found that these small peptides contained the trans-3 and cis-4 isomers of hydroxyproline as well as trans-4 ones and that their production was not completely inhibited by alpha, alpha-dipyridyl, and iron chelator and effective inhibitor of enzyme-mediated hydroxylations. It is known that oxygen or hydrogen peroxide in the presence of metal can hydroxylate proline and other aromatic compounds. We show here that reduced oxygen derivatives can hydroxylate both free and polypeptide-bound proline and lysine, and that scavengers of hydroxyl radicals suppress, but do not completely inhibit, this reaction. Reduced oxygen derivatives can be generated in normal and pathological circumstances, and some of the low-molecular-weight hydroxyproline and hydroxylysine peptides found in cell and organ cultures might be derived from these derivatives and therefore do not reflect collagen turnover, but rather some other cellular activity. PMID- 6256662 TI - Effects of ATP and vanadate on calcium efflux from barnacle muscle fibres. AB - Calcium ions carry the inward current during depolarization of barnacle muscle fibres and are involved in the contraction process. Intracellular ionized calcium ([Ca2+]i) in barnacle muscle, as in other cells, is kept at a very low concentration, against a large electrochemical gradient. This large gradient is maintained by Ca2+ extrusion mechanisms. When [Ca2+]i is below the contraction threshold, Ca2+ efflux from giant barnacle muscle fibres is, largely, both ATP dependent and external Na+ (Na+0) dependent (see also refs 5,6). When [Ca2+]i is raised to the level expected during muscle contraction (2-5 muM), most of the Ca2+ efflux from perfused fibres is Na0 dependent; as in squid axons, this Na+0 dependent Ca2+ efflux is ATP independent. Orthovanadate is an inhibitor of (Na+ + K+) ATPase and the red cell Ca2+-ATpase. We report here that vanadate inhibits ATP-promoted, Na+0-dependent Ca2+ efflux from barnacle muscle fibres perfused with low [Ca2+]i (0.2-0.5 microM), but has little effect on the Na+0-dependent, ATP-independent Ca2+ efflux from fibres with a high [Ca]i (2-5 microM). Nevertheless, ATP depletion or vanadate treatment of high [Ca2+]i fibres causes an approximately 50-fold increase of Ca2+ efflux into Ca2+-containing lithium seawater. These results demonstrate that both vanadate and ATP affect Ca2+ extrusion, including the Na+0-dependent Ca2+ efflux (Na-Ca exchange), in barnacle muscle. PMID- 6256663 TI - Photolabelling of cholera toxin subunits during membrane penetration. AB - There has been much speculation about the mechanism by which cholera toxin exerts its effect on the cytoplasmic side of the membranes with which it interacts. After the pentamer of B subunits (5B) binds to membrane receptors, particularly the monosialylganglioside GM1, the disulphide-linked dimer A1SSA2 (which together with 5B constitutes the complete toxin) is thought to penetrate the membrane, perhaps through a channel formed by 5B and become reduced so that A1SH units reach the cytoplasm and stimulate adenylate cyclase. Evidence for this mechanism is circumstantial. If it is correct, a compound which will specifically label intramembranous sections of the toxin should label the channel-forming B subunits but not the channel-contained A1 subunit. We have tested this prediction with a photoreactive glycolipid compound and have obtained the opposite result. Therefore, we propose that only the A1 subunit enters the membrane and we provide here data on the kinetics of that process. PMID- 6256664 TI - Alpha 2 adrenoceptors in rat brain: the divalent cation site. PMID- 6256665 TI - Methyldopa produces central inhibition of parasympathetic activity in the cat. AB - alpha-Methyldopa (10-100 mg/kg i.v.) produced a dose-dependent pupillary dilation in anaesthetized cats which was antagonized by subsequent administration of yohimbine hydrochloride (0.5 mg/kg i.v.). The peak effects were observed approximately 2-3 h after injection. This alpha-methyldopa-induced mydriasis was present only when the parasympathetic innervation to the iris was intact. Prior treatment with yohimbine (0.5 mg/kg i.v.) 30 min before alpha-methyldopa also antagonized the mydriatic effect, whereas pretreatment with phenoxybenzamine (2.5 mg/kg i.v.) did not. In contrast, phenoxybenzamine, but not yohimbine, effectively antagonized the pupillary dilation produced by adrenaline (0.3-10.0 microgram/kg i.v.). These results suggest that alpha-methyldopa produces mydriasis in the cat by means of CNS inhibition of tonic outflow from the oculomotor nucleus and that an alpha-adrenergic inhibitory mechanism may be involved. This conclusion is supported further by experiments in which direct measurements of ciliary nerve activity were made. PMID- 6256667 TI - Complete blockade by phenoxybenzamine of alpha 1- but not of alpha 2-vascular receptors in dogs and the effects of propranolol. AB - In pithed dogs pressor responses to phenylephrine were completely inhibited 1 h after phenoxybenzamine 20 mg/kg i.v., but those to norepinephrine were only partially inhibited. The pressor effects of norepinephrine in phenoxybenzamine treated animals were inhibited by yohimbine, 2.0 mg/kg i.v., but not by prazosin, 0.5 mg/kg i.v. In animals treated with phenoxybenzamine, 20 mg/kg i.v., plus propranolol, 5.0 mg/kg i.v., the partially restored pressor response to epinephrine, and the responses to norepinephrine, were completely inhibited by yohimbine, 2.0 mg/kg i.v., partially inhibited by corynanthine, 5.0 mg/kg i.v., but not affected by prazosin, 0.5 mg/kg i.v. In additional animals treated with phenoxybenzamine plus propranolol, yohimbine, 10, 50, 200 and 500 microgram/kg i.v., caused dose-related inhibition of both the partially restored pressor response to epinephrine, and the pressor responses to norepinephrine. It is concluded that: 1) phenoxybenzamine completely blocks alpha 1, but not alpha 2 vascular receptors; 2) the pressor effect of norepinephrine in phenoxybenzamine treated animals, and the partially restored pressor effect of epinephrine in phenoxybenzamine-propranolol-treated animals, are both mediated by alpha 2 vascular receptors which are resistant to blockade by phenoxybenzamine. PMID- 6256666 TI - Presynaptic actions of 4-aminopyridine and gamma-aminobutyric acid on rat sympathetic ganglia in vitro. AB - Responses to bath-applications of 4-aminopyridine(4-AP) and gamma-aminobutyric acid (GABA) were recorded intracellularly from neurones in the rat isolated superior cervical ganglion. 4-aminopyridine (0.1-1.0 mmol/l) usually induced spontaneous action potentials and excitatory postsynaptic potentials (EPSPs), which were blocked by hexamethonium. Membrane potential was unchanged; spike duration was slightly increased. Vagus nerve B- and C-fibre potentials were prolonged. In 4-AP solution (0.2-0.3 mmol/l), GABA (0.1 mmol/l), 3 aminopropanesulphonic acid or muscimol evoked "bursts" of spikes and EPSPs in addition to a neuronal depolarization. These "bursts", which were not elicited by glycine, glutamate, taurine or (+/-)-baclofen, were completely antagonised by hexamethonium, tetrodotoxin or bicuculline methochloride. It is concluded that: (a) 4-AP has a potent presynaptic action on sympathetic ganglia; (b) presynaptic actions of GABA can be recorded postsynaptically in the presence of 4-AP; and (c) the presynaptic GABA-receptors revealed in this condition are similar to those on the postsynaptic membrane. PMID- 6256668 TI - A neurally mediated inotropic effect of veratridine and cevadine on isolated guinea-pig papillary muscle. AB - The positive inotropic effect of veratridine and cevadine was investigated in the isolated, isometrically contracting guinea-pig papillary muscle. The increase of the force of the rested-state contraction, elicited after incubation of the resting muscle with veratridine or cevadine, served as a measure of the neurally mediated, sympathomimetic effect of these alkaloids. Concentrations exceeding 5 mumol/l veratridine or 15 mumol/l cevadine produced concentration-dependent increases of the force of the rested-state contraction. These concentrations are larger than those causing the maximum positive inotropic effect on muscles contracting continually at a rate of 1 Hz. The positive inotropic effect of 30 mumol/l veratridine as manifested by the rested-state contraction was absent in the presence of 100 nmol/l tetrodotoxin and in muscles from reserpine-pretreated animals. It was significantly inhibited by 50 nmol/l (-)-propranolol, but not by the same concentration of (+)-propranolol. The effect of 30 or 60 mumol/l cevadine was likewise absent in catecholamine-depleted preparations. It is concluded that the indirect inotropic effect of veratridine or cevadine, which is attributed to their noradrenaline-releasing effect on intracardiac nerves, requires higher concentrations than the direct positive inotropic effect, which is a consequence of the increased transsarcolemmal influx of Na ions into the myocardial cell. PMID- 6256671 TI - Nephroblastoma and renal mesenchymal tumor induced in rats by N-nitrosoethyl- and N-nitrosomethylurea. AB - Rats treated prenatally with N-nitrosoethylurea or with N-nitrosomethylurea developed nephroblastomas, renal mesenchymal tumors and epithelial tumors (adenomas and carcinomas) of the kidneys. 15 nephroblastomas and 59 mesenchymal tumors were examined histologically. Nephroblastomas were encapsulated growths composed of dark cells, forming primitive tubules similar to those seen in the rat embryonal kidney and in human Wilms' tumor. Mesenchymal renal tumors showed an infiltrative growth and consisted of fibroblast-like cells, smooth muscles and angiomatous areas with the engulfed pre-existing tubules. These growths are similar to the mesenchymal renal tumors induced in the rat by N nitrosodimethylamine. Nephroblastoma and mesenchymal renal tumor are considered to be separated entities, the first corresponsing to the epithelial variant of human Wilms' tumor and the second to congenital mesoblastic nephroma. PMID- 6256669 TI - Possible mechanisms for inotropic actions of vanadate in isolated guinea pig and rat heart preparations. AB - The mechanism of inotropic actions of vanadate studied in isolated, electrically stimulated atrial and ventricular muscle preparations of rat or guinea-pig heart. Vanadate produced a negative inotropic effect in guinea-pig left atrial preparations associated with a marked shortening of the action potential plateau. In guinea-pig papillary muscle, or rat atrial or ventricular muscle preparations, vanadate produced a positive inotropic effect, which was not affected by either propranolol, phentolamine or metiamide. The positive inotropic effect was observed when action potential duration was either increased or decreased. Inotropic concentrations of vanadate failed to significantly alter the ouabain sensitive 86Rb+-uptake, an estimate of sodium pump activity, or tissue concentration of cyclic AMP in electrically stimulated preparations. In partially depolarized rat atrial preparations in which fast sodium channels were inactivated in the presence of a high concentration of K+ (22 mmol/l), vanadate restored electrical activity (calcium-dependent action potentials) and the contraction, similar to isoproterenol. This action of vanadate was abolished by Mn2+, a slow channel inhibitor, but not by tetrodotoxin. The characteristic of vanadate- and isoproterenol-restored preparations, however, were substantially different. Moreover, vanadate failed to restore the contraction or action potential in partially depolarized guinea pig atrial preparations unlike isoproterenol. These results indicate that vanadate may either enhance or inhibit slow channels in cardiac muscle. PMID- 6256670 TI - Involvement of central GABA receptors in the regulation of the urinary bladder function of anaesthetized rats. AB - Cystometric recordings were performed in pentobarbitone anaesthetized rats and the effects of gammaaminobutyric acid (GABA) mechanisms on urinary bladder function were evaluated as their influence on a bladder hyperactivity induced by 1-dihydroxyphenylalanine (L-DOPA) after peripheral decarboxylase inhibition. The bladder response was inhibited by intracerebroventricular (i.c.v., 4th ventricle) injections of GABA (250 microgram), muscimol (0.2 microgram) and glycine (1,000 microgram) as well as by systemically administered muscimol (4 mg/kg) and diazepam (2 mg/kg). Intravenous (i.v.) bicuculline, but not i.v. strychnine, antagonized the inhibitory actions of intraperitoneal (i.p.) and i.c.v. muscimol and i.v. diazepam while the opposite was true for the inhibitory action of i.c.v. glycine. In rats not pretreated with L-DOPA, i.p. administration of bicuculline (4 mg/kg) after 15 min caused prominent detrusor contractions that were prevented by an infracollicular brain transection. It is suggested that GABA synapses in the pontinemesencephalic brain region may be involved in the modulation of urinary bladder function. PMID- 6256672 TI - [Epilepsy associated with Islet-cell adenoma (author's transl)]. PMID- 6256673 TI - [Some practical aspects of suicide prevention (author's transl)]. PMID- 6256674 TI - [Results of surgical treatment of anaplastic cerebral gliomas]. AB - In the years 1971 through 1977 247 patients with anaplastic cerebral gliomas were treated. Out of this material a group of 119 patients was completed who were treated only surgically and had follow-up examinations or responded to an inquiry form sent to them. In the light of this follow-up study it was established that the survival time was shortest, only up to 6 months, in the patients with preclinical symptoms lasting up to 3 months. In the remaining patients the survival time was longer, reaching over one year in 11 cases and over 2 years in 3 cases. In view of the mode of spread of recurrent neoplasm the authors differentiated exophytous expansion - with the infiltration filling the postoperative tissue defect and extending beyond its margins, infiltrative expansion - with the infiltration spreading on the walls of the postoperative tissue defect, destructive expansion - with the neoplasm infiltrating and destroying the brain tissue. Two latter modes of growth were most frequent and led to death of the patients without producing signs of intracranial hypertension. PMID- 6256675 TI - [Invasive growth of malignant parotid tumor in the posterior fossa (author's transl)]. PMID- 6256677 TI - [The association of cerebral aneurysm with malignant brain tumor--report of a case (author's transl)]. AB - A rare case was reported in which a brain tumor was associated with a cerebral aneurysm. A 59-year-old woman was admitted with right spastic hemiparesis and motor aphasia. She was in somnolence and complained of headache. She had two attacks of loss of consciousness about 12 years previously. Since then she had right spastic hemiparesis and motor aphasia as sequelae. Preoperative CT scan and carotid angiograms showed a malignant brain tumor in the left temporal region and an anterior communicating artery aneurysm. Operation was performed in one stage. At first the neck of the aneurysm was clipped by right sphenoidal approach and the tumor was partialy removed by left temporal approach. The histological diagnosis was glioblastoma multiforme. The cerebral aneurysm associated with brain tumor should be treated as soon as possible. The operative result in our case was good. PMID- 6256676 TI - [Scanning electron microscopy of human cultured gliomas (author's transl)]. AB - Tumor tissues of glioblastoma multiforme, astrocytoma and medulloblastoma, maintained up to 21--28 days by gelfoam organ culture technique, were examined by scanning electron microscopy (SEM). Glioblastoma multiform has irregular cell surface and many cytoplasmic folds. Astrocytoma has many fibrils. The fibrils have smooth surface and are coiling. Fibrils of piloid astrocytoma are smooth and cylindrical. The focal thickness of fibrils are associated with so-called Rosenthal fiber. Capillary of astrocytoma has irregular surface and marked tortuosity. Medulloblastoma is composed of non-fibrillated round tumor cells. The tumor cells touch each other with short cell processes. These findings seemed to correspond to the malignancy of original tumor. Comparative observation of medulloblastoma maintained by monolayer cell culture with one maintained by organ culture, using light microscopy and scanning electron microscopy, was done. And medulloblastoma in monolayer culture was proliferated to two types of cells. One is epitheloid cell with taper cell processes, and the other is stellate cell with fine processes. In most organ culture, feature of cells corresponded to those observed in original surgical material by light microscopy. PMID- 6256678 TI - Some recent advances in the clinical aspects of multiple sclerosis. AB - Recent work on the clinical aspects of multiple sclerosis is reviewed with particular regard to symptomatology: New approaches to clinical symptoms and the identification of more subtle impairments are illustrated by recent studies of visual function in M.S. patients; pathophysiology: It is now widely appreciated that the dysfunction observed in patients is not determined solely by histologically demonstrable demyelination. The function of the demyelinated neuron is highly variable, being dependent upon factors which may change from day to day. Recent ideas about 'neuro-electric blocking factors' and other factors that may influence demyelinated neurons and hence symptoms are discussed; diagnosis: tests on C.S.F., electro-physiological and psychophysiological tests and computer tomography as aids to diagnosis and the controversy over 'specific' blood tests are reviewed; course and prognosis: Long term follow-up studies confirm that, in a significant proportion of cases, the course of M.S. may be benign and have identified some early prognostic indices; TREATMENT: The results of trials of symptomatic (spinal cord stimulation) and would-be curative therapies (such as dietary supplementation with poly-unsaturated fatty acids and immunosuppression) are briefly discussed. PMID- 6256679 TI - Cycloleucine encephalopathy. AB - Cycloleucine, a non-metabolizable amino acid analogue produces status spongiosus in cerebral white matter of rats and mice as well as a distinctive lesion of astrocytes. Its mechanisms of action include competition with natural amino acids from transport across the blood-brain barrier leading to inhibition of entry of circulating amino acids into brain, interference with ribosomal RNA maturation, and blockage of transmethylation reactions, including the conversion of homocystine to methionine. Cycloleucine also affects the kidney, producing aminoaciduria. Electron microscopy of cerebral white matter reveals spongiform changes of myelin sheaths caused by separation of myelin lamellae along intraperiod lines and accumulation of whorls of filaments in astrocytes. The myelinopathy is dose related and its toxicity is cumulative due to its long half life in animals. The findings are discussed with reference to other spongiform myelinopathies, including status spongiosus observed in homocystinuria and other aminoacidurias. PMID- 6256681 TI - [Opiate receptors and sleep. II. Effects of micro-injection of ethyl alcohol and pentobarbital in the median thalamus, periaqueductal gray matter and nucleus of the tractus solitarius of the rabbit (author's transl)]. AB - There is an analogy between sleep EEGs produced by microinjections of morphine in the bulbo-mesencephalo-thalamic recruiting system and EEGs seen during anesthetic induced sleep. Many studies in the last 10 years have claimed cross-tolerance and cross-dependence between opiates and ethyl alcohol. Opiates, ethyl alcohol and pentobarbital have many common metabolic actions in the central nervous system. Like morphine, microinjections of optimal equimolar doses of ethyl alcohol and pentobarbital in the bulbo-mesencephalo-thalamic sleep-inducing system of the rabbit produce sleep EEGs with abundant fast activity, which is blocked by naloxone (2 mg/kg i.v.) or by microinjections (160 micrograms) into the same structures. However, there is neither binding nor displacement by naloxone of ethyl alcohol or pentobarbital from the opiate receptor. It is thus probable that, via an as yet unknown mechanism, ethyl alcohol and pentobarbital promote the release of endorphins or peptides, which are specific ligands of all or some opiate receptors. PMID- 6256680 TI - Calcium rather than cyclic AMP as the physiological intracellular regulator of prolactin release. PMID- 6256682 TI - The spectrum of peripheral neuropathy in myeloma. AB - The records of 20 patients with typical or sclerotic (sclerotic or mixed sclerotic and lytic) multiple myeloma and peripheral neuropathy who were seen during a 13-year period were analyzed to determine the natural history of the neuropathy. In the 10 patients with typical multiple myeloma, the clinical pattern was heterogeneous. Chemotherapy for multiple myeloma did not affect the neuropathy. The 10 patients who had sclerotic myeloma presented in a relatively homogeneous manner, with a predominantly motor neuropathy. Tumoricidal radiation therapy to localized plasmacytomas resulted in pronounced improvement in the neuropathy of two patients, mild improvement in three, and mild improvement in the endocrine abnormalities of one patient. PMID- 6256684 TI - Brachial plexus lesions in patients with cancer: 100 cases. AB - In patients with cancer, brachial plexus signs are usually caused by tumor infiltration or injury from radiation therapy (RT). We analyzed 100 cases of brachial plexopathy to determine which clinical criteria helped differentiate tumor from radiation injury. Seventy-eight patients had tumor (34 with previous RT), and 22 had radiation injury. Severe pain occurred in 80% of tumor patients but in only 19% of patients with radiation injury. The lower trunk (C7-8, T1) was involved in 72% of the tumors, and 32% also had epidural tumors. Seventy-eight percent of the radiation injuries affected the upper plexus (C5-6). Horner syndrome was more common in tumor, and lymphedema in radiation injury. The time from RT to onset of plexus symptoms, and the dose of RT, also differed. For symptoms within 1 year of RT, doses exceeding 6000 R were associated with radiation damage, whereas lower doses were associated with infiltration. Therefore, painless upper trunk lesions with lymphedema suggest radiation injury, and painful lower trunk lesions with Horner syndrome imply tumor infiltration. PMID- 6256683 TI - Chronic central nervous system demyelination in mice after JHM virus infection. AB - The pathogenesis of murine hepatitis virus, strain JHM, was studied in 6- and 12 week-old C57/BL mice. There was 100% mortality in the 6-week-old mice after intracerebral inoculation. The lesions were characterized by necrotizing encephalomyelitis, without demyelination. Intracerebral inoculation of 12-week old animals, however, resulted in no morbidity or mortality. The 12-week-old animals showed transient virus replication in the brain, spinal cord, and liver, which was cleared by day 14. Histologic examination showed evidence of ongoing demyelination, concomitant remyelination, and hydrocephalus ex vacuo. Although viral antigen was demonstrated by immunofluorescence in the central nervous system of these animals, no infectious virus was recovered, and immunosuppression regimens did not potentiate the disease. PMID- 6256685 TI - [Changes in rat liver enzymatic activity induced by CT 1341 (althesin) administration]. AB - Six enzyme activities with different intracellular localization were selected for a study of the metabolic effects caused by CT 1341 (Althesin). Glucose-6 phosphato-phosphatasic, ATP-asic and aryl-4-hydroxylasic (hydroxylasic aniline) activities are in fact localised in the microsomial fraction whereas glucose-6 phosphato-dehydrogenasic, 6-phosphogluconic dehydrogenasic and UDP-glucoso dehydrogenasic activities are to be found in the soluble fraction. The Althesin doses used varied between 0.75 and 6 mg/kg body weight, but only the latter dose is capable of triggering significant variations. With the exception of glucose-6 phosphato-phosphatase, which falls markedly, and ATPase which behaves discontinuously, the other enzyme activities increase to reach their maximum between the 15th and 30th minute after treatment. The diminution in glucose-6 phosphato-phosphatasic activity is attributable to a drug-induced change in the microsomial membranes. The increase in other activities, on the other hand, is connected with drug metabolisation. On a par with other steroid compounds, CT 1341 to be eliminated, must go through a hydroxylation reaction requiring higher production of NADPH. Its elimination also requires a higher concentration of UDP glucuronic. The data obtained with separate injection of the active principles making up the drug did not give results in agreement with those obtained with the commercial product and, for the present, no final conclusions can be drawn. PMID- 6256686 TI - [Relation between cytomegalovirus infection and the so-called intolerance to azathioprine in renal transplantation]. AB - Renal transplant recipients can develop hepatic function abnormalities or severe leucopenia after transplantation. Generally it is thought to be due to azathioprine intolerance and patients are treated by curtailment of immunosuppressive therapy, being subsequently at risk to lose their allograft because of rejection. Evidence of Cytomegalovirus (CMV) infection is also common after renal transplantation. It is generally thought that the majority of these infections are asymptomatic, but they can be accompanied by leucopenia and/or hepatic function abnormalities. Sixty-nine renal transplant recipients have been studied for at least three months in order to investigate the relationship between CMV and azathioprine intolerance after transplantation. Twenty-five out of 58 patients who underwent seroconversion to CMV (a fourfold or greater rise in titer of CMV antibodies) after transplantation or who had a high CMV titer (greater than or equal to 1 : 16) prior to transplant, developed azathioprine intolerance. None of 11 patients who before renal transplantation had low CMV titers and who did'nt underwent seroconversion did not tolerate azathioprine. Therefore the Authors advance the hypothesis that azathioprine intolerance following renal transplantation can be often due to an asymptomatic and unknown CMV infection. PMID- 6256687 TI - [Association of primary malignant neoplasms in the same patient]. AB - The Authors have examined the problem concerning the presence of "Double malignancies" in the same patient, on the basis of a review of the literature and of an investigation of their own case material (nine patients: six with double solid tumours and three with a solid tumour and an associated haematologic neoplasia). The Authors discuss the time sequence of the two neoplastic processes and the immunological pattern (T and B lymphocytes) of all cases. PMID- 6256688 TI - [Radiological signs of a disease that is dying out: hepato-splenic atrophy and cholangiocarcinoma after administration of thorium dioxide (Thorotrast)]. AB - The cases of two patients with radio-opaque residues of contrast medium (Thorotrast) in the abdomen, at the level of the liver, the spleen and certain lymph node groups of the hepatic hilum and the pancreas are reported. In one of the two patients (both of whom had undergone examination with this contrast medium in the '40s) necropsy showed the existence of cholangiocarcinoma. It is therefore considered useful to recall the X-ray signs typical of this pathology, which is dying out after the abandonment of thorium dioxide as an X-ray contrast medium. PMID- 6256689 TI - [Viral respiratory infections]. AB - A brief account of the general features of viruses and their importance in the biological world is followed by a description of the main viruses responsible for respiratory infections in man, with particular reference to matters of morphology, epidemiology, pathology, and (where possible) prophylaxis. Lastly, the modalities for the isolation of such viruses and the main serological reactions employed in diagnosis are explained. PMID- 6256690 TI - [Clinical aspects of viral respiratory infections]. AB - The Authors deal with some clinical aspect of the commonest types of respiratory tract viral infections. After a description of the characteristics of the most important diseases (common cold, ARD, influenza, viral pneumonia) they deal with some particular problem difficult in resolution, both from a pathogenetic and clinical viewpoint and quite constant bacterial over infection, the cardiac complications, th possible evolution to fibrosis and the relationship between viral infections and asthma. The nowadays problem of immunological and chemotherapeutic prevention of viral infections, particularly of type A influenza, is also discussed. PMID- 6256691 TI - Uptake and cellular degradation of low-density lipoprotein. AB - In vitro data suggest that low-density lipoprotein (LDL) is bound to specific receptors located in pits on the surface of fibroblasts by a high-affinity process and subsequently undergoes catabolism in lysosomes. This binding seems to be mediated by ionic interaction between LDL and its receptor, the latter being totally or partially absent from the fibroblasts of patients with familial hypercholesterolaemia (FH). In vivo data suggest that LDL is also catabolised by a concentration-dependent, low-affinity pathway which is probably mainly located in the liver. LDL catabolism is reduced in FH and after saturated fat feeding, whereas polyunsaturated fat has the reverse effect. Hypocatabolism of LDL alters LDL composition, accelerates atherosclerosis and may lead to premature death from coronary heart disease. PMID- 6256692 TI - Role of low-density and high-density lipoproteins in atherogenesis. AB - Among the cholesterol-carrying lipoproteins, low-density lipoproteins (LDL) have been associated with coronary heart disease as a risk factor while high-density lipoproteins (HDL) appear to protect against coronary heart disease. According to studies with cells in tissue culture, control mechanisms of receptor-mediated LDL uptake are important in maintaining the cholesterol balance within the arterial cells. HDL may be a vehicle for transporting cholesterol from peripheral cells to the liver. Recent results, derived from studies of patients affected with Tangier disease (absence of HDL in plasma), favor the hypothesis that HDL precursors (e.g. surface remnants of chylomicrons) may be more potent in cholesterol uptake than mature HDL. PMID- 6256693 TI - Dietary effects on certain adrenal cortical functions in the rat. AB - The rate-limiting step in adrenal steroidogenesis is associated with the mitochondrial-cytochrome-P450scc-dependent production of pregnenolone from cholesterol. This sterol side-chain cleavage reaction is influenced by the supply of cholesterol to the mitochondria. Cholesterol is stored as cholesterol esters while the cytosol contains a hormone-sensitive cholesterol ester hydrolase. This enzyme is activated by phosphorylation involving a cyclic AMP-dependent protein kinase and ATP; this enzyme preferentially attacks cholesterol oleate or cholesterol linoleate. The lipid composition of the adrenal cortex is influenced by diet so that animals on a low-fat diet tend to store cholesterol oleate and as the linoleate content of the diet is increased, the cholesterol linoleate content of the adrenal cortex increases. Animals maintained on a high erucate diet tend to store large amounts of cholesterol erucate in the adrenal cortex; such animals have an impaired adrenal cortical function. Animals maintained on a low-fat diet (marginally deficient in essential fatty acids), a linoleate-replete diet or a moderate erucate diet, all exhibited normal responses to ACTH and normal corticosterone production rates. PMID- 6256694 TI - A clinico-pathological study of two patients with Cushing's disease. AB - The clinical and autopsy findings are described in two patients with Crushing's disease who died five days and 18 years following bilateral adrenalectomy. In each case tomography of the pituitary fossa was normal but examination of the pituitary revealed a 5 to 6 mm basophilic adenoma in the antero-inferior aspect of the gland. The first patient failed to show suppression of urinary oxogenic steroids during administration of high dose dexamethasone. The second patient had functioning adrenal autografts in skeletal muscle 18 years after adrenalectomy. The clinico-pathological correlation of these two patients supports modern re emphasis on the aetiology of Cushing's disease as a primary pituitary tumour and its treatment by selective trans-sphenoidal hypophysectomy. PMID- 6256695 TI - A survey of antibodies to Aujeszky's disease virus in pigs. PMID- 6256696 TI - [Effect of 5'-adenosine monophosphate and cyclic 3',5'-adenosine monophosphate on the ability of guinea pig bone marrow precursor cells to form fibroblast-like cell colonies in vitro]. AB - The effect of 5'-AMP and cyclic 3',5'-AMP on the ability of cells--precursors of bone marrow to form colonies of fibroblast-like cells in vitro was studied in the guinea pig. No reliable effect of both substances (within the limits of 10(-5) to 10(-8) M) on the formation of fibroblast colonies in vitro by the cells- precursors of bone marrow was shown. No differences were established in the size of colonies between the experimental and control variants. PMID- 6256697 TI - Use of absorbable sutures in outpatient cataract surgery and lens implantation. PMID- 6256698 TI - Studies on neonatal calf diarrhoea caused by rotavirus: transmission of the disease and attempted vaccination of colostrum-deprived calves. AB - Mild to severe scouring could be produced in colostrum-deprived calves with tissue culture-adapted rotavirus and feacal material from field cases of calf diarrhoea. The feaces of experimentally infected calves contained rotavirus for at least 3 days. Pathogenic bacteria were presented in one calf only and this calf also showed the most severe gastroenteritis. Eight calves were vaccinated with a live rotaviral calf diarrhoea vaccine and subsequently challenged with infective rotavirus. Mild scouring was observed after vaccination, but the calves remained normal after challenge. Rotavirus particles were detectable in the faeces for a few days after vaccination and challenge. PMID- 6256699 TI - Diagnostic methods for herpes simplex infection: a review. AB - An antiviral treatment modalities appear in ever-increasing numbers, the need for precise viral diagnosis becomes essential. A review of the current diagnostic methods, including virus isolation, serology, biopsy, and cytology, is presented. The newer, more sensitive immunoperoxidase stain and ELISA are discussed. The needs, methods, and benefits of an accurate viral diagnosis are stressed. PMID- 6256700 TI - Adenoid cystic carcinoma of the head and neck. Controllable and uncontrollable factors in treatment and prognosis. AB - Histological re-examination of 64 adenoid cystic carcinomata showed that 15 of them were different tumours, mainly adenocarcinomata. The remaining 40 adenoid cystic carcinomata were solid in 6 cases, cribriform in 24 cases and tubular in 14 cases. No precise classification was possible in 5 cases of adenoid cystic carcinoma. Uncontrollable factors important for the prognosis of adenoid cystic carcinomata included the histological type and the site of the tumour: major salivary glands (28 cases), area of paranasal sinuses (11 cases) and minor salivary glands (10 cases). Adenoid cystic carcinomata of tubular type or situated in minor salivary glands had a relatively favourable prognosis related to survival rate, 'state of health' and tendency to recurrence. Controllable factors exerted a favourable influence on the commonly poor prognosis of adenoid cystic carcinomata. They included an early diagnosis and, because of the tendency to recurrence, radical surgery and radiotherapy. The poor long-term prognosis of this tumour was due to a tendency to local recurrence (80% of cases) and mainly haematogenous metastasis (37% of cases). Lymphogenous metastasis was less frequent (6% of cases). PMID- 6256701 TI - [Liver cirrhosis and hepatocellular carcinoma]. PMID- 6256702 TI - [Phosphonate esterase activity in human serum (author's transl)]. AB - A simple methodology for the spectrophotometric assay of phosphonate esterase activity in human serum samples is described, featuring incubation at 30 degrees C in a medium containing p-nitrophenol and phenyl-phosphonic acid ester. Reproducibility of the method as well a mean values in normal patients vs age and sex are reported. Serum activity appears to be increased almost exclusively during pregnancy or administration of estrogenic drugs (as oral contraceptives or in prostate neoplasms). PMID- 6256703 TI - Clinicopathologic study of minute and small early gastric cancer. Histogenesis of gastric cancer. AB - According to the report by Sano, and our previous study of 900 cases of early gastric cancer, multiple gastric cancers were seen in 73 patients (8 percent). The remaining 827 had solitary cancers. In comparison with solitary cancers, multiple gastric cancers were seen more often in males, with the predominant histologic type being well-differentiated adenocarcinoma. A higher incidence (28 percent) of elevated types (I and IIa) was noticed in multiple gastric cancer cases than in solitary cancers (19 percent). The incidence of ulceration within the cancerous lesion was low (35 percent) in multiple cancers but high (69 percent) in solitary cancers. These differences between solitary and multiple cancers observed in 900 early gastric cancer cases were also noted between solitary and multiple cancers in the present series, regardless of the size of lesions. PMID- 6256704 TI - Endocrinologic pathology of functioning adrenocortical tumors. PMID- 6256705 TI - Synovial sarcoma. A study of 23 biphasic and 17 probable monophasic examples. PMID- 6256706 TI - Ultrastructural aspects of human breast lesions. PMID- 6256708 TI - Recent advances in the study of mineral pneumoconiosis. PMID- 6256707 TI - Calcification processes. PMID- 6256709 TI - Drugs and chemicals excreted in breast milk. PMID- 6256710 TI - Computed tomographic diagnosis of calcified inferior vena cava thrombus in a child with Wilms' tumor. AB - A calcified thrombus in the inferior vena cava of infants and children may be imaged by computed tomography. The precise location of the calcification within the inferior vena cava may be confirmed by computed tomographic scanning during injection of intravenous contrast material. PMID- 6256711 TI - Effect of antidiuretic hormone and dibutyryl cAMP upon the urinary concentrating capacity in neonatal piglets. AB - In 18-one-day-old anesthetized piglets, the effects of 1-deamino-8-D-arginine vasopressin (DDAVP) with and without administration of dibutyryl adenosine 3':5' monophosphate (DBcAMP) upon the urinary concentrating system were studied. Supramaximal doses of 20 microgram DDAVP per kg body weight did not affect fractional water and fractional urea excretion, urinary flow rate, and relative urinary osmolarity. The same dose combined with DBcAMP (0.2 mg/kg body weight per min) changed these parameters significantly. This increase in the responsiveness of the urinary concentrating system to DDAVP by DBcAMP was paralleled by a significant increase in urinary and plasma cyclic adenosine 3':5'-monophosphate concentration and a tremendous increase in the medullary cyclic adenosine 3':5' monophosphate content (2.5 X 10(5) pmoles/g medulla) as compared to the controls (6.4 X 10(2) pmoles/g medulla) and the animals which received DDAVP without DBcAMP (8.0 X 10(2) pmoles/g medulla). To exclude the possibility that the increased medullary cyclic adenosine 3':5'-monophosphate production might be caused by degradation of the dibutyryl derivative, in vitro studies with [3H]DBcAMP were performed. Incubation of labeled DBcAMP with a renal medulla homogenate of a 1-day-old piglet for 30, 60, and 90 min did not decrease the amount of [3H]DBcAMP. PMID- 6256712 TI - Formation of acidic phospholipids in rabbit lung during perinatal development. PMID- 6256714 TI - [Perinatal infections]. PMID- 6256715 TI - The sodium pump. PMID- 6256716 TI - [Effects of adriamycin on radiation sensitivity of cultured human lung cancer cells (author's transl)]. PMID- 6256713 TI - Aldosterone response to prolonged ACTH infusion in juvenile hypertension. AB - The effects of a continuous 5-day ACTH infusion (40 units/24 hr) on plasma aldosterone (aldo) concentration and urinary excretion of aldosterone pH 1 conjugate, tetrahydroaldosterone and free aldo were investigated in 6 normotensive children, and 7 children with hypertension of unknown origin. In both groups, an initial rise of plasma aldo and all urinary aldo metabolites and a subsequent fall were observed during the ACTH test. The decline in plasma aldo correlated significantly with a decrease in plasma renin activity and serum K+. There was, however, evidence for another regulatory factor of aldo secretion during ACTH infusion because on a low salt diet. ACTH produced a similar aldo pattern which could not be attributed to the changes in plasma renin activity or serum K+. Urinary excretion of both free aldo and tetrahydroaldosterone, a metabolite formed in the liver, showed a slower decrease during ACTH infusion than aldosterone pH 1 conjugate, which is of renal origin. The change in pattern of urinary aldo metabolites may be caused by a relative increase of the free, nonprotein bound plasma fraction of aldo and an enhanced metabolism of aldo in the liver during ACTH infusion. Neither in the baseline state nor during the ACTH test was there a difference between the normotensive and the hypertensive group in any of the aldo parameters. PMID- 6256717 TI - [Endemic Balkan nephropathy (author's transl)]. AB - Endemic Balkan nephropathy (EBN) is a chronic interstitial nephritis which may occur at any age and may affect several members of the same family. The condition is slowly progressive and can more easily be diagnosed in its advanced than in its early stages. Early symptoms include severe anaemia and increased plasma aminoacids, alkaline phosphatases and gamma 2 and alpha globulins. Eosinophilia is not uncommon. Loss of urine concentration power and high beta 2 microglobin urinary levels are among the earliest signs of EBN and of considerable diagnostic value. Renal biopsy shows invasive sclerosis, IgG and IgA deposits in glomerular vessels and Bowman's capsule walls and, characteristically, osmiophilic granulations within the mitochondria of proximal tubule cells; the mitochondria may in due course burst and disappear. Atrophic or dystrophic changes may develop in the stomach, upper intestine and liver. The aetiology of EBN remains undetermined, but chronic intoxication with drinking water polluted by silicates released during soil erosion seems to be the most probable cause. Silicates may act directly or by inducing an immune process. PMID- 6256718 TI - [Cylindroma obstructing the left primary bronchus. Endoscopic ablation by YAG laser (fiberoscopy)]. PMID- 6256719 TI - The effect of norepinephrine and depolarizing agents on 14C-glucose metabolism in rat brain. AB - Hexose monophosphate (HMP) shunt activity was examined by an isotopic method based on measurements of the conversion of 1-(14)C-glucose and 6-(14)C-glucose to 14CO2, yielding 1-(14)C/6-(14)C ratio in slices from different parts of rat brain in the range of 2.5 to 5.0 after 15 min incubation of the slices at 37 degrees C. The influence of noradrenaline (NE), high K+ concentration, ouabaine and glutamate was evaluated. NE (1 mM) caused a pronounced stimulation of HMP activity in cortical, hypothalamic and striatal slices. This effect was observed only in the presence of ascorbate in the incubation medium. The experiments with dibutyrylc-AMP, theophylline and alpha and beta adrenoreceptor blocking agents suggest that the cyclic AMP-dependent mechanism is not involved in the NE stimulation of HMP shunt. Moreover, neither basal glucose metabolism (glycolysis and 14C-glucose incorporation into 14CO2, lipid, protein and nucleic acid fractions) nor SH group level were affected by the neurotransmitter. PMID- 6256720 TI - Opiate A and B receptors in the rat striatum. AB - Studies involving binding of 3H-naloxone to crude synaptosomal fraction from the rat striatum have revealed that the striatum contains opiate receptors. Scatchard analysis data indicate that KD = 70.92 nM and Bmax = 0.37 pmole per milligram of proteins. The experiments carried out in the absence and presence of Na+ in the incubating medium have shown that morphine and azidomorphine behave as agonists of the opiate receptor in the striatum, while cyclopropylmethylazidomorphine acts as an antagonist. It is concluded that the striatal opiate receptors are predominantly of type B. PMID- 6256722 TI - Minimal steric difference study of structural requirements for the luteinizing hormone-releasing hormone (LH-RH) receptor. AB - Quantitative structure-activity relation for amino acid substitution analogues of the LH-RH decapeptide were established by means of the receptor site mapping procedure based upon minimal steric differences. For a series of 17 analogues of LH-RH, obtained by substitutions of the C-terminal Gly-NH2 residue, a corelation coefficient r = 0.93 was obtained, for a series of 7 analogues, obtained by substitutions of the Leu7 residue, r = 0.95 was obtained. The shape of the LH-RH receptor regions interacting with the C-terminal of the decapetide and with the Leu7-side chain is inferred from this study. PMID- 6256721 TI - Analgesic activity and opiate receptor affinity of new derivatives of N butylpiperidine. AB - The three newly synthesized derivatives of N-butylpiperidine 1-butyl-4-phenyl-4 isonicotinoylaminoethylpiperidine (BG 25), 1-buty-isonicotinoylpiperidine (BG 26) and N-(1-butyl-4-phenyl-4-piperidinoyl) tetrahydropapaverine (BG 9) were evaluated for analgesic activity and opiate receptor affinity. All the three compounds showed analgesic activity both in hot-plate and flinch-squeak-jump test in mice, BG 9 being the most potent. The affinity of the compounds to opiate receptor was moderate (in comparison with pentazocine): the affinity of BG 9 was much greater than that of BG 25 and BG 26. The compounds showed a pronounced inhibitory action in stimulated guinea-pig ileum preparation; this was reversible by naloxone. As evaluated on pA basis, all three investigated compounds showed moderate antagonistic activity. Also in this respect BG 9 was more active than the other two compounds. Cholinolytic and strong spasmolytic properties were observed in isolated rat ileum preparation for BG 9 only. PMID- 6256724 TI - [Tumour-specific antibodies in the regional lymph nodes of patients with lung cancer (author's transl)]. PMID- 6256723 TI - [Variations of plasmatic cyclic nucleotides in the asthmatic patient (cyclic adenosine monophosphate and cyclic guanosine monophosphate) (author's transl)]. AB - The present paper studies in asthmatic patients the variations of the plasmatic levels of cAMP and cGMP as control of an eventual adrenergic beta receptors trouble. The first part includes the study of relations of the plasmatic level of nucleotides with the parameters: age, sex, time of sampling in a population of normal subjects (n = 91) and asthmatic patients (n = 203). There is a significant correlation between the age and the level of plasmatic cAMP in normal subject (r = 0.63) as well as in asthmatic patients (r = 0.73). Age for age, there is no difference between the plasmatic levels of controls and the asthmatic patients. The cGMP level is stable, identical in asthmatic (18 p mu +/- 1.74/ml) and in normal subjects (16.84 p mu +/- 2.77 p mu/ml). No nycthemeral rhythm has been revealed. The second part examines the variations of plasmatic levels of cyclic nucleotids during pharmacodynamic assay: methylcholine, beta blocking drugs, spray and subcutaneous sympathomimetics, corticotherapy. No variation of cAMP and cGMP was shown after inhalation of methylcholine or injection of beta blocking drugs able to induce or to reveal a bronchospasm. On the other hand the sympathomimetic drugs, whatever mean of introduction, bring a significant increase of the average level of cAMP going from 40 p mu/ml +/- 5.09 to 101 p mu/ml +/- 4.67 in healthy subject and of 49.42 p mu/ml +/- 10.10 to 74.38 p mu/ml +/- 13.7 in asthmatic patients. The difference in variation amplitude between asthmatic and control subjects is significant, the asthmatic patients responding less to a beta adrenergic stimulation. The plasmatic cGMP remains unchanged during the assay. Corticotherapy does not modify the initial level of cAMP but restores the response to a beta adrenergic stimulation. Inhalation of cAMP dibutyryl restores the bronchial permeability. The study of the variations of plasmatic levels of cAMP reveals a hyposensitivity of the whole of beta adrenergic receptors in asthmatic patients. The former varies in time and can be normalized either spontaneously or by corticotherapy. PMID- 6256725 TI - [Chemotherapy-cum-irradiation in the treatment of inoperable small-cell and anaplastic large-cell bronchogenic carcinoma (author's transl)]. PMID- 6256726 TI - [Histological classification of primary thymic tumors]. PMID- 6256727 TI - [Cystosarcoma phylloides of the breast and bilateral breast cancer. Case report]. PMID- 6256728 TI - An improved method for the preparation of human placental syncytiotrophoblast microvilli. AB - A simple procedure is described for the further purification of placental microvillus preparations. Based on previously published methods for the isolation of microvilli from other tissues, it depends on the preferential aggregation of containing structures by Mg2+. In the purified microvillus preparation, the two placental microvillar marker enzymes, alkaline phosphatase and 5'-nucleotidase, were enriched 24-fold and were obtained in 5 per cent yield. Five other microvilla enzymes were also further enriched by the Mg2+-treatment. Marker enzymes for other subcellular components showed that this treatment completely removed contamination by mitochondria and endoplasmic reticulum and contamination by lysosomes was decreased three-fold. (Na+ + K+)-activated ATPase was depleted by the Mg2+-treatment as was beta2-microglobulin. PMID- 6256729 TI - [Pharmacological analysis of the role of dorsal hippocampus adrenergic effects in the central mechanisms of ovulation and compensatory ovarian hypertrophy in rats]. AB - In experiments on mature female rats it was shown that L-DOPA administration restores normal ovulation in rats after the dorsal hippocampus destruction and related partial ovulation blockade. Pharmacological analysis after microinjections of alpha- and beta-adrenoblockers into the dorsal hippocampus region has shown that alpha- and beta-adrenoreception of the dorsal hippocampus plays a definite role in the regulation of gonadotropin secretion. However, the effect of phentolamine injection on the rat ovulatory reaction was less pronounced than under conditions of this hippocampus region destruction. The beta adrenoblocker propranolol injected into the dorsal hippocampus inhibited compensatory hypertrophy of the ovaries in hemicastrated rats, decreased the hypophyseal FSH content and did not influence ovulation. PMID- 6256730 TI - [Angiotensin II receptors in the adrenals]. PMID- 6256731 TI - [Differential diagnosis of pulmonary tuberculosis and sarcoidosis (review of the literature)]. PMID- 6256732 TI - Construction of a flash-activated cyclic electron transport system by using bacterial reaction centers and the ubiquinone-cytochrome b-c1/c segment of mitochondria. AB - Single-turnover electron transfer within the mitochondrial complex III has been studied by combining, in solution, the isolated complex from bovine heart with detergent-solubilized reaction centers of Rhodopseudomonas sphaeroides. Initiation of electron transfer by short flash activation resulted in the prompt oxidation of cytochrome c and reduction of cytochrome b. The subsequent reduction of ferricytochrome c was observed to be concomitant with the oxidation of the ferrocytochrome b, both reactions being inhibited by the addition of actimycin A. The rate of electron transfer through complex III is dependent upon the ambient redox potential poise in a way that is consistent with the presence of a redox component, presumably analogous to the photosynthetic ubiquinone Qz, which is an obligatory intermediate in electron transfer between cytochromes b and c. These results demonstrate cyclic electron transfer in a constructed assembly of mitochondrial complex III, cytochrome c, and photochemical reaction centers. PMID- 6256733 TI - Redox conformation changes in refined tuna cytochrome c. AB - Tuna ferrocytochrome c and ferricytochrome c have been refined independently at high resolution (1.5 A and 1.8 A) to crystallographic residual errors of 17.3% and 20.8%, respectively. Small but significant conformational differences are seen surrounding a buried water molecule that is hydrogen bonded to Asn-52, Tyr 67, and Thr-78. In the oxidized state, this water molecule is 1.0 A closer to the heme and the heme has moved 0.15 A out of its heme crevice; both changes lead to a more polar microenvironment for the heme. Chemical modification studies, patterns of evolutionary conservatism, structural differences in bacterial cytochromes, and x-ray studies all agree that the "active site" for cytochrome c is bounded by lysines 8, 13,27, 72, 79, 86, and 87 (thus containing the evolutionary conservative 72-87 loop) and has the buried water molecule just below its surface and the opening of the heme crevice slightly to one side. PMID- 6256734 TI - Ion-transport chain of cytochrome oxidase: the two chain-direct coupling principle of energy coupling. AB - Cytochrome oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1) couples the aerobic oxidation of ferrocytochrome c to the cyclical transport of monovalent cations or to the active transport of monovalent and divalent cations. This transport capability is mediated by an intracomplex ion-transport chain of two protein-bound molecules of cardiolipin per molecule of cytochrome oxidase. Cardiolipin in a two-phase system shows the identical ionophoric pattern as does the cytochrome oxidase coupled system. A molecular model of the cardiolipin chain suggests the possibility of a cage-like structure through which cations can be transferred from phosphate group to phosphate group. The ion-transport chain and the electron-transport chain are anchored to the same set of subunits (I+IV); the close proximity of the two chains argues for the direct coupling of electron and cation flow. The ion-transport chain of cytochrome oxidase provides an introduction to the molecular mechanisms by which ions are moved across membranes in energy-coupling systems. PMID- 6256735 TI - Cytoskeletal constraint of the beta-adrenergic receptor in frog erythrocyte membranes. AB - A fluorescence receptor binding assay, based upon the high-affinity beta adrenergic receptor antagonist propranolol, is utilized to probe the microenvironment of the antagonist-receptor complex in the frog (Rana catesbeiana) erythrocyte membrane. The technique of steady-state fluorescence depolarization is applied to the propranolol-receptor complex, allowing quantitation of the rotational relaxation time of the complex. It is found that the complex is dynamically constrained at 20 degrees C. However, in the temperature range 6-10 degrees C a sharp reversible release of constraint is observed. It is further demonstrated that the addition of drugs that are known to specifically disrupt the cytoskeleton (colchicine, vincristine, and vinblastine) causes a similar but irreversible release of constraint at 20 degrees C. Cytochalasin B has a much smaller influence on the rotational mobility of the propranolol-receptor complex than do the other drugs that disrupt the cytoskeleton. Amphotericin B is without effect on the rotational constraint of the complex. Binding of the antagonist [3H]dihydroalprenolol is not influenced by colchicine. A model is proposed which postulates that cytoskeletal elements are linked to the antagonist-receptor complex. Antagonist binding does not result in cytoskeletal release, whereas agonist binding is postulated to lead to dissociation of the agonist-receptor complex from the cytoskeleton, thereby activating adenylate cyclase. PMID- 6256736 TI - Mitochondrial DNA polymorphism: evidence that variants detected by restriction enzymes differ in nucleotide sequence rather than in methylation. AB - Restriction enzyme analysis of mtDNAs for the purpose of determining sequence divergence rests on the assumption that variant recognition sites differ with respect to sequence and not methylation. This assumption was tested on two mtDNAs, A and B, which are distributed throughout the laboratory rat population and which can be distinguished by a number of restriction enzymes. The mtDNAs were cloned and the nucleotide sequences of corresponding small HindIII fragments, in which a variant EcoRI site occurs, were determined. Evidence that the fragments differ in sequence and not methylation is as follows: (i) The cloned mtDNA yielded the same fragment pattern as did native mtDNA when treated with EcoRI, Hha I, HinfI, and Hae III; (ii) three nucleotide replacements were found in the 169-base pair fragment, A.T in equilibrium G.C, A.T in equilibrium G.C, T.A in equilibrium G.C; (iii) one of these replacements, A.T in equilibrium G.C at position 80, accounts for the presence of the EcoRI site in the type A and its absence in the type B mtDNA. Examination of the sequence leads to the suggestion that these three nucleotide replacements are silent; i.e., they would not lead to amino acid substitutions in a possible encoded protein. PMID- 6256737 TI - In vivo regulation of rat liver 3-hydroxy-3-methylglutaryl-coenzyme A reductase: enzyme phosphorylation as an early regulatory response after intragastric administration of mevalonolactone. AB - Although substantial evidence supports the conclusion that 3-hydroxy-3 methylglutaryl-coenzyme A (HMG-CoA) reductase [mevalonate:NADP+ oxidoreductase (CoA-acylating), EC 1.1.1.34] is the major regulatory enzyme in cholesterol biosynthesis, the molecular events involved in the in vivo regulation of this enzyme have remained obscure. To study this problem, rats were given a single 100 mg dose of mevalonolactone by intragastric tube. The rats were sacrificed 20 or 60 min later, and liver microsomes were prepared by ultracentrifugation. Two phases of inhibition of microsomal HMG-CoA reductase were observed. The first phase of inhibition, observed 20 min after mevalonolactone administration, was completely reversed by preincubation of the microsomes with purified phosphoprotein phosphatase. The second phase of inhibition, observed 60 min after mevalonolactone administration, was not reversed by phosphoprotein phosphatase. The reactivation of liver microsomal HMG-CoA reductase by phosphoprotein phosphatase was blocked by potassium fluoride or by phosphoprotein phosphatase inhibitor. Results obtained by immunotitration also showed that microsomal HMG CoA reductase obtained from animals killed 20 min after mevalonolactone administration was significantly activated by phosphoprotein phosphatase treatment of the microsomes. These findings demonstrate that phosphorylation of rat liver HMG-CoA reductase is an early in vivo regulatory response after intragastric administration of mevalonolactone. PMID- 6256738 TI - The inverted repeat as a recognizable structural feature in supercoiled DNA molecules. AB - The single-strand-specific endonuclease S1 from Aspergillus oryzae introduces highly selective cleavages into supercoiled covalently closed circular DNA molecules, but not into their previously linearized counterparts. The cleavage sites are inverted repeats of unit length between 9 and 13 base pairs, separated by a nonrepetitious 2-6 base pairs. Such regions may adopt hairpin or similar structures stabilized by the negative superhelix density and may constitute recognition sites for cellular proteins. PMID- 6256739 TI - Construction and analysis of simian virus 40 origins defective in tumor antigen binding and DNA replication. AB - We have inserted a 311-base pair DNA fragment containing the simian virus 40 (SV40) origin of DNA replication, the early promoter, and the tumor (T) antigen binding sites into a bacterial plasmid and cloned it. This recombinant plasmid, pSV01, binds to a purified T antigen in vitro and replicates in monkey cells when supplied with large T antigen. A series of deletion mutations was generated in the origin sequences of pSV01 DNA by mutagenesis in vitro. The replication of these mutant DNAs in monkey cells was compared with their ability to bind to purified D2 protein. Mutant DNAs deficient in binding to D2 protein also exhibit reduced levels of replication in monkey cells. These findings provide biochemical evidence that the initiation of SV40 DNA synthesis may involve a direct interaction of T antigen with sequences at the origin of replication. PMID- 6256740 TI - Three-dimensional structure of a protein from scorpion venom: a new structural class of neurotoxins. AB - The three-dimensional crystal structure of variant-3 toxin from the scorpion Centruroides sculpturatus Ewing has been determined at 3 A resolution. Phases were obtained by use of K2PtCl4 and K2IrCl6 derivatives. The most prominent secondary structural features are two and a half turns of alpha-helix and a three strand stretch of antiparallel beta-sheet, which runs parallel to the alpha helix. The helix is connected to the middle strand of the beta-sheet by two disulfide bridges; a third disulfide bridge is located nearby. Several loops extend out of this dense core of secondary structure. The largest loop is joined to the COOH terminus of the molecule by the fourth disulfide bridge. The overall shape of the molecule resembles a right-hand fist: the alpha-helix runs along the knuckles of the fist; the beta-sheet lies along the second and third joints of the fingers; the thumb is defined by two short loops that are composed of residues 16-21 and residues 41-46; the wrist corresponds to the COOH-terminal stretch of residues 52-65 and a loop composed of residues 5-14; and the second joint of the little finger is near the NH2 terminus of the molecule. The alpha carbon backbone displays a large flat surface that lies along the second joints of the fingers and the heel of the hand in the fist model. Several of the conserved residues in the scorpion neurotoxins are clustered on this surface, which may play a role in interactions of scorpion toxins with sodium channels of excitable membranes. PMID- 6256742 TI - Homology exists among the transforming sequences of avian and feline sarcoma viruses. AB - Fujinami sarcoma virus (FSV) of chickens does not contain nucleotide sequences related to the src gene of Rous sarcoma virus, but it carries unique sequences of at least 3000 bases, which are likely to code for the transforming protein of this virus. Using radioactive DNA complementary to FSV-unique sequences, we investigated the relatedness of FSV to other sarcoma-leukemia retroviruses in vertebrates. Under conditions of moderate stringency, no cross-hybridization was detected between FSV cDNA and RNAs of Rous sarcoma virus, Y73 avian sarcoma virus, several representative avian acute leukemia viruses, or Abelson murine leukemia virus. This cDNA, however, did hybridize with RNA of PRCII sarcoma virus of chickens to the extent of 56%. In addition, FSV cDNA was found to hybridize with RNAs of Gardner-Arnstein and Snyder-Theilen strains of feline sarcoma virus to the extent of 27% and 19%, respectively, but not with RNA of McDonough feline sarcoma virus. Studies on thermal denaturation of hybrids showed that the melting temperatures of the heteroduplexes of the FSV cDNA with RNAs of PRCII and Gardner Arnstein feline sarcoma virus were 7 degrees C and 12 degrees C lower, respectively, compared with the melting temperature of the homologous hybrid of FSV, and suggested less than 10% mismatching in both heteroduplexes. These results indicate that nucleotide sequences closely related to at least a part of FSV-unique sequences are present in the genomes of other sarcoma viruses obtained in chickens and in cats. PMID- 6256741 TI - Mechanism of action of glucagon on hepatocyte phosphofructokinase activity. AB - Addition of glucagon to isolated hepatocytes reduced the activity of 6 phosphofructokinase (ATP:D-fructose-6-phosphate 1-phosphotransferase, EC 2.7.1.11) and pyruvate kinase (ATP:pyruvate 2-O-phosphotransferase, EC 2.7.1.40). Phosphorylation contributed to the inhibition of pyruvate kinase, but several lines of evidence indicated that this reaction was not responsible for the inhibition of phosphofructokinase. First, the increase in phosphorylation in intact cells induced by increasing the concentration of glucagon did not correlate well with the decrease in enzyme activity. Second, phosphorylation of phosphofructokinase induced by addition of cyclic AMP and Mg2+-ATP or by addition of Mg2+-ATP and the catalytic subunit of the cyclic AMP-dependent protein kinase to hepatocyte extracts had no effect on enzyme activity. Third, ammonium sulfate precipitation of the enzyme from extracts of cells incubated with glucagon abolished the hormone effect. The effect could be restored, however, by the addition of a phosphofructokinase-free extract from glucagon-treated cells to the ammonium sulfate-treated enzyme from either untreated or glucagon-treated cells. These results suggest that the inhibition of phosphofructokinase by glucagon is due to changes in the level of an allosteric effector(s). PMID- 6256743 TI - Isolation of yeast genes with mRNA levels controlled by phosphate concentration. AB - A library of DNA from the yeast, Saccharomyces cerevisiae, was constructed in phage lambda Charon 4 vector and then screened by differential plaque filter hybridization for genes induced by phosphate starvation. Two EcoRI fragments of 7.9 and 5.0 kilobase pairs that contained such genes were isolated. These cloned fragments may each carry one of the several copies of the genes for the repressible acid phosphatase of yeast. The fragments were use to examine mRNA levels of these genes in regulatory mutants of acid phosphatase. PMID- 6256745 TI - Exchange kinetics of the Schiff base proton in bacteriorhodopsin. AB - Using rapid mixing techniques and resonance Raman spectroscopy, we have found that the 1H/2H exchange time for the Schiff base proton of bacteriorhodopsin in purple membrane is 4.7 msec, when experiments are carried out at pH 2 or pH 7 at room temperature in the dark. We argue that diffusion of neutral water into the membrane is fast on this time scale. Also, model Schiff bases in solution have a pKa between 6 and 7, and we show that such model Schiff bases have much faster exchange rates. Therefore, we conclude that the Schiff base proton in bacteriorhodopsin is protected from interaction with the medium, probably by interaction with a protein group, and this would account for a pKa considerably higher than 6-7. PMID- 6256746 TI - Iron-sulfur proteins: spin-coupling model for three-iron clusters. AB - Recent Mossbauer and EPR studies of two ferredoxins and of aconitase have given evidence for a three-iron cluster, probably of a [3Fe-3S] type. The studies of the oxidized EPR-active centers have shown that the three iron sites are characterized by significantly different magnetic hyperfine coupling constants. For the ferredoxin from Azotobacter vinelandii, for instance, we have observed A1 = -41 MHz, A2 = +18 MHz, and [A3] = 5 MHz. We demonstrate here that the magnetic properties of the clusters can be explained with a simple model of three high spin ferric ions (S = 5/2) exchange-coupled to a system spin S = 1/2. The model assumes isotropic exchange and different couplings between the iron sites. The results show that the three sites have intrinsic hyperfine interactions similar to those of ferric rubredoxin; the differences in the observed interactions reflect the geometrical features of spin coupling. Furthermore, the three exchange coupling constants are equal within a factor of 2. This implies that the three-iron cluster is a single covalently linked structure and should not be considered as a [2Fe-2S] cluster weakly coupled to a third iron atom. PMID- 6256744 TI - Escherichia coli RNA polymerase in vitro mimics simian virus 40 in vivo transcription when the template is viral nucleoprotein. AB - We have used a low-salt detergent-free extraction procedure on cells infected with simian virus 40 to obtain viral nucleoprotein late after infection. Addition of EScherichia coli RNA polymerase and ribonucleotide triphosphates to the viral minichromosomes permitted transcription of RNA from viral templates. This synthesis was initiated predominantly within a fragment of DNA spanning 0.67 to 0.76 map unit on the genome. The synthesis from this region proceeded primarily along the "late" strand in a clockwise direction. These results were in contrast to the synthesis obtained with naked viral DNA in which initiation occurred on other regions of the genome and from which transcription proceeded counterclockwise along the early strand. These findings indicate that the nucleoprotein template or factors tightly associated with it may be responsible for site(s) and strand selection in transcription of simian virus 40. PMID- 6256747 TI - Proton longitudinal relaxation investigation of histidyl residues of normal human adult and sickle deoxyhemoglobin: evidence for the existence of pregelation aggregates in sickle deoxyhemoglobin solutions. AB - Proton nuclear magnetic resonance longitudinal-relaxation-rate measurements have been used to investigate the molecular events that occur during the early stages of the polymerization process of sickle hemoglobin. The longitudinal relaxation rates (T1-1) of the C2 protons of 11 observable surface histidyl residues in normal human adult and sickle hemoglobin in the deoxy state were measured in 0.1 M bis[(2-hydroxyethyl)imino]tris(hydroxymethyl)methane (pH 6.8) in 2H2O. These proton resonances in hemoglobin occur at a position 1.5-5.0 ppm downfield from that of residual water in 2H2O. The T1-1 values for the C2 protons of several surface histidyl residues in sickle hemoglobin in the deoxy state were sensitive to the temperature and the concentration of hemoglobin, factors known to have a profound effect on the polymerization process of sickle hemoglobin. For hemoglobin concentrations of 13.5% or less and temperatures of 25 degrees C or less, the T1-1 values in sickle hemoglobin solutions were the same as the corresponding values in normal hemoglobin, except for the C2 proton of beta 2 histidine, which had a larger T1-1 value. When the temperature or the hemoglobin concentration was increased (i) several additional histidine resonances in sickle hemoglobin solutions had larger T1-1 values than the corresponding ones in normal hemoglobin and (ii) the differences between the T1-1 values (sickle versus normal hemoglobin) of these histidine resonances as well as that of the beta 2 histidine resonance gradually increased. It is proposed that these results reflect the formation of small aggregates in the deoxygenated sickle hemoglobin solutions before gelation. In this model, the histidyl residues for which the T1-1 values are greatly increased in sickle hemoglobin solutions as compared with those in normal hemoglobin are viewed as being located in or near the "contact" areas between sickle hemoglobin molecules within the pregelation aggregates. Thus, this magnetic resonance technique can also be used to identify the intermolecular contacts in the polymerization of sickle hemoglobin. PMID- 6256748 TI - Kinetic models suggest bimolecular reaction steps in axonal Na+-channel gating. AB - Abstract kinetic models that can successfully simulate the ion-permeability features of axonal Na+ channels suggest the presence of bimolecular reaction steps in the activation of the channels. A chemically plausible interpretation of minimum complexity is described. The implied chemical formalism is highly suggestive of an activator-controlled gating system with strong similarities to the acetylcholine-regulated system. Conformational changes that underlie the ion conductance changes are suggested to possess a greater sensitivity to the membrane field in axonal parts of excitable membranes than at synaptic parts. This would allow axonal permeability changes to be energetically regulated more conservatively than is observed for synaptic ion channels. Axonal K+ channels with delayed activation kinetics would serve to reverse the increase in membrane permeability to Na+ with a minimum of chemical dissipation. PMID- 6256749 TI - Prostaglandin I2 modifies both prolactin binding capacity and fluidity of mouse liver membranes. AB - The objective of this study was to determine if prostaglandins alter the fluidity of hepatic membranes and if this, in turn, modifies their ability to bind prolactin. Liver homogenates of adult C3H female mice incubated with 1-1000 nM prostaglandin A1, A2, B2, F1 alpha, 6-keto-F1 alpha, E1, E2, I2, or thromboxane B2 provided the 100,000 X g membrane pellets for subsequent ovine prolactin binding and membrane fluidity studies. Only membrane preparations treated with prostaglandin I2 showed an increase in specific binding of ovine prolactin. The effect (40-50%) was maximal at 100 nM prostaglandin I2 after 30 min of incubation and was due to an increase in the number of receptor sites. Under the same conditions, prostaglandin I2 induced a 17% decrease in membrane microviscosity. These data suggest that specific prostaglandins may modulate the number of prolactin receptors in vivo by modifying the fluidity of the lipid bilayer and the subsequent ease with which receptors can assume active configurations within the matrix. PMID- 6256750 TI - Active proliferation of Rous sarcoma virus-infected, but not normal, chicken heart mesenchymal cells in culture medium of physiological composition. AB - Normal as well as Rous sarcoma virus-infected chicken pectoral and chicken embryo fibroblasts proliferate actively in a plasma containing medium of physiological ion concentrations (Ca2+, 1.2 mM; Mg2+, 0.7 mM). Reduction of medium calcium and magnesium concentrations is necessary to achieve selective quiescence of normal fibroblasts in these cell systems. By contrast, normal chicken heart mesenchymal cells proliferate only sluggishly (one doubling or less during a 6-day period) in a plasma containing medium of physiologic ion concentrations, whereas Rous sarcoma virus-infected heart mesenchymal cells proliferate actively (more than four doublings during an initial 2-day phase of exponential growth). The chicken heart mesenchymal cell system therefore has great potential for studies of the mechanism that initiates cell replication and of the failure in cellular regulatory processes that is responsible for the autonomous initiation of replication of neoplastic cells. From comparison of the chicken heart mesenchymal cell system to dialyzed plasma-based systems in which 3T3 cells tend to proliferative quiescence, it is argued that this proliferative quiescence of 3T3 cells is a result of cell starvation and is not physiologically meaningful. PMID- 6256752 TI - Glycosaminoglycans that bind cold-insoluble globulin in cell-substratum adhesion sites of murine fibroblasts. AB - Glycosaminoglycans (GAGs) and glycoprotein-derived glycopeptide from mouse BALB/c3T3 and simian virus 40-transformed 3T3 whole cells or their adhesion sites, which are left bound to the serum-coated tissue culture substratum after detachment of cells mediated by [ethylenebis-(oxyethylenenitrilo]tetraacetic acid (EGTA), were analyzed for specific binding to Sepharose columns derivatized with cold-insoluble globulin (CIg). CIg is the serum-contained form of fibronectin and is required for the adhesion of these fibroblasts to the substratum. Of the various GAGs present in these fractions of either cell type, only the highly N sulfated sequences of heparan sulfate and a small subset of dermatan sulfate bind to CIg-Sepharose. There was no detectable binding of glycopeptide, undersulfated heparan sulfate, the various chondroitin species, or hyaluronate. Adhesion sites from newly attaching cells were greatly enriched in CIg-binding heparan sulfate when compared to long-term-growth adhesion sites or EGTA-detached cells. Various properties of binding were determined. The reference standard standard GAGs heparin (or heparan sulfate) and dermatan sulfate were able to displace bound radiolabeled adhesion site GAG from the column, whereas the other GAGs had no effect. CIg has been shown to be the only adhesion-promoting activity in the serum layer of this culture system. Because these fibroblast adhesion sites do not contain collagen, which could potentially mediate adhesion to the substratum bound CIg, these data support other evidence that multivalent heparan sulfate proteoglycans mediate substratum adhesion of these cells by coordinate binding to fibronectin on the cell surface and CIg on the substratum. PMID- 6256751 TI - Cytoskeletal F-actin patterns quantitated with fluorescein isothiocyanate phalloidin in normal and transformed cells. AB - Actin in cultured fibroblasts is organized into a complex set of fibers. Patterns of organization visualized with antibody to actin are similar but not identical to those visualized with fluorescein isothiocyanate-phalloidin (Fl-phalloidin), a chemical that binds to F-actin polymer with a dissociation constant of 2.7 X 10( 7) M [Wulf, E., Deboben, A., Bautz, F. A., Faulstich, H. & Wieland, T. (1979) Proc. Natl. Acad. Sci. USA 76, 4498-4502]. Fl-phalloidin reveals that transformed cells have fewer, finer, and shorter F-actin-containing structures than do normal cells. Two-color fluorescence microscopy of single cells reveals that F-actin staining by Fl-phalloidin picks out the cytoskeletal cables more sharply than does antibody to actin, due to a reduced intracellular background fluorescence. This improved resolution permits sorting of cellular Fl-phalloidin patterns into four classes ranging in organization from 90% of the cytoplasm occupied by large cables to the absence of detectable cables. Reproducible differences in pattern distributions between normal and transformed cell lines have been quantitated. Fl phalloidin together with rhodamine-based indirect antibody to simian virus 40 tumor antigen reveals a direct relationship between the degree of pattern change and simian virus 40 nuclear antigen expression in intermediate transformed 3T3 cell lines [Risser, R. & Pollack, R. (1974) Virology 59, 477-489]. PMID- 6256753 TI - Endogenous electrical currents in the water mold Blastocladiella emersonii during growth and sporulation. AB - We have explored the pattern of electrical currents generated by single cells of the water mold Blastocladiella emersonii at several stages of its life cycle. Extracellular currents were measured with a vibrating probe constructed after the design of Jaffe and Nuccitelli [Jaffe, L. F. & Nuccitelli, R. (1974) J. Cell Biol. 63, 614-628]. In growing cells positive current, of the order of 1 microA/cm2, enters the rhizoid and leaves from the thallus; circumstantial evidence suggests that protons carry much of the current. Sporulation is associated with reversal of the current pattern, such that positive current enters the thallus and leaves from the rhizoidal region; the ions that carry the current have not been identified. These current patterns appear to play a role in the spatial localization of fungal growth and development. PMID- 6256754 TI - Mutant of avian erythroblastosis virus defective for erythroblast transformation: deletion in the erb portion of p75 suggests function of the protein in leukemogenesis. AB - Previous studies have shown that td359 AEV, a mutant of avian erythroblastosis virus (AEV), is unable to transform erythroblasts in vitro or in vivo but is capable of transforming fibroblasts in vitro and of causing sarcomas in chicks. In this paper we show that the mutant synthesizes a gag-gene related protein (delta p75) which is about 1000 daltons smaller than the protein, p75, induced by wild-type AEV. The mutant protein lacks 3 of the approximately 53 lysine-arginine tryptic peptides resolved in p75 and also contains an additional peptide. By cleavage of delta p75 with p15 protease and analysis of the fragments for size and peptide composition, the deletion in delta p75 could be located in the non gag region of the molecule. In contrast, with p40 AEV, a second AEV-specific protein synthesized in in vitro translation experiments, there is no change in size of translation products obtained from td359 AEV RNA. Our data provide direct evidence that p75 is required for erythroblast transformation. PMID- 6256755 TI - Altered distributions of the cytoskeletal proteins vinculin and alpha-actinin in cultured fibroblasts transformed by Rous sarcoma virus. AB - It was recently shown by combined immunofluorescence and interference reflection microscopy that a protein named vinculin, along with alpha-actinin, is concentrated at focal adhesion plaques inside cultured normal fibroblasts [Geiger, B. (1979) Cell 18, 193-205]. These plaques are the discrete, isolated sites of strong adhesions formed between the ventral surfaces of the cells and the substrata on which they are grown. We show that after transformation of fibroblasts by Rous sarcoma virus a majority of the cells have many fewer focal adhesion plaques and now exhibit a cluster of small patches that are immunolabelled for both vinculin and alpha-actinin. Such a cluster (rosette) is located near the ventral surface of the cell, usually partly under the nucleus. The significance that these altered distributions of vinculin and alpha-actinin may have for the rounding up and loss of adherence of transformed cells is discussed. PMID- 6256756 TI - Receptor-mediated internalization of fluorescent gonadotropin-releasing hormone by pituitary gonadotropes. AB - A bioactive, fluorescent derivative of gonadotropin-releasing hormone, < Glu-His Trp-Ser-Tyr-D-Lys(N epsilon-tetramethylrhodamine)-Leu-Arg-Pro-Gly-NH2, was prepared. This peptide retained high-affinity binding (apparent dissociation constant, 3 nM) to the receptor for gonadotropin-releasing hormone and was utilized for microscopic visualization and localization of gonadotropin-releasing hormone receptors in cultured rat pituitary cells. The fluorescently labeled receptors were initially distributed uniformly on the cell surface and formed patches, which subsequently internalized (at 37 degrees C) into endocytic vesicles. These processes were dependent on specific binding sites for the rhodamine-labeled peptide to gonadotrope cells. Cluster formation and internalization were markedly reduced in the absence of Ca2+, which is required for gonadotropin secretion. It is possible that cluster formation, microaggregation, and internalization of gonadotropin-releasing hormone receptors may be important in eliciting biological effects or for the observed loss of tissue responsiveness after desensitization due to exposure to the homologous hormone. PMID- 6256757 TI - Maternal inheritance of human mitochondrial DNA. AB - Human mitochondrial DNA was obtained from peripheral blood platelets donated by the members of several independent families. The samples were screened for nucleotide sequence polymorphisms between individuals within these families. In each family in which we were able to detect a distinctly different restriction endonuclease cleavage pattern between the parents, the progeny exhibited the maternal cleavage pattern. Informative polymorphisms were detected for Hae II (PuGCGCPy) in a three-generation family composed of 33 members, for HincII (GTPyPuAC) in a two-generation family composed of four members, and for Hae III(GGCC) in a two-generation family composed of four members. The Hae II polymorphism was analyzed through all three generations in both the maternal and paternal lines. The results of this study demonstrate that human mitochondrial DNA is maternally inherited. The techniques described for using peripheral blood platelets as a source of human mitochondrial DNA represent a convenient way to obtain data on mitochondrial DNA variation in both individuals and populations. PMID- 6256758 TI - Initiation of DNA replication in a ColE1-type plasmid: isolation of mutations in the ori region. AB - We have constructed a plaque-forming hybrid phage, lambda SN4, which behaves as a composite replicon of the lambda phage and a mini-ColE1 plasmid. From the hybrid phage, plaque-type mutants altered in the ability to replicate as a ColE1 replicon were isolated. These mutations were designated as cer, signifying ColE1 replication defective. One of such mutants, lambda SN4cer6, was studied further. The mutant DNA was unable to replicate in vivo if expression and function of its lambda replicon were inhibited. The defect could not be complemented in trans. DNA sequence determination of the mutant phage revealed a single base pair (bp) alteration, C-G to T-A, at 160 bp upstream from the ori site of its ColE1 replicon. From lambda SN4cer6, revertants were obtained that had regained function of the ColE1 replicon, and they could be classified into two groups that showed a full and a partial recovery in the rates of ColE1-driven DNA synthesis. DNA sequence determination of revertant DNA indicated that the former group contained true revertants, T-A to C-G, at the cer6 site, whereas one of the partial revertants was found to sustain a secondary-site mutation, G-C to A-T at 187 bp upstream of the ori site. It was possible to construct a hairpin structure that starts by hydrogen bonding of bases at the site -160 and -187. PMID- 6256759 TI - Immunoreactive helix-destabilizing protein localized in transcriptionally active regions of Drosophila polytene chromosomes. AB - A highly purified helix-destabilizing protein (HDP) obtained from rat liver has been used to elicit specific, high-titer anti-HDP sera in rabbits. These antisera show immunological crossreaction with single-stranded DNA binding proteins from several very diverse eukaryotic sources, including Drosophila embryos. The use of such antisera in the labeling of Drosophila salivary gland chromosomes by indirect immunofluorescence shows concentrations of immunoreactive HDP in many regions, but especially in chromosome puffs. There is a striking localization of HDP in heat shock puffs known to be sites of new transcription. The pattern of HDP distribution seems to implicate a transcriptional role, with some specificities independent of puffing itself. PMID- 6256760 TI - Resistance of simian virus 40-transformed hamster cells to the cytolytic effect of activated macrophages: a possible factor in species-specific viral oncogenicity. AB - Simian virus 40 (SV40)-transformed hamster cells were relatively resistant to the lytic effect of activated macrophages from animals with chronic intracellular infections. Conversely, SV40-transformed mouse and rat cells and adenovirus 2 transformed hamster cells were highly susceptible to destruction by tumoricidal activated macrophages. The pattern of resistance or susceptibility of SV40 transformed rodent cells was the same whether activated macrophage effectors were obtained from mice, random-bred hamsters, or the inbred LSH hamsters from which some of the SV40-transformed hamster lines were derived. The results suggest that resistance of transformed cells to macrophage-mediated cytolysis may explain in part the species-specific oncogenicity of this DNA virus. PMID- 6256761 TI - Role of adenylate cyclase in immunologic release of mediators from rat mast cells: agonist and antagonist effects of purine- and ribose-modified adenosine analogs. AB - The initial monophasic rise in cyclic AMP beginning 5-15 sec after bridging of rat mast cell IgE-Fc receptors precedes the secretion of granule constituents, thereby implying a causal relationship. Direct evidence for a relationship between IgE-dependent transmembrane activation of adenylate cyclase and granule secretion was provided by the capacity of purine-modified (R site active) and ribose-modified (P site active) adenosine analogs, respectively, to augment and suppress mediator release while simultaneously increasing and decreasing the activity of adenylate cyclase. R site stimulation alone does not cause granule secretion but augments the rate and magnitude of IgE-Fc receptor-induced secretion, reflecting the coupled relationship of such receptors. Inhibition of adenylate cyclase at the P site attenuates the rise in cellular cyclic AMP and suppresses IgE-dependent mediator release in a parallel and superimposable dose response fashion. Further, the relationship between the attenuation in the rise in cyclic AMP and the diminution in immunologic mediator release is linear with the regression line passing through the origin, indicating a direct relationship between the IgE-dependent activation of adenylate cyclase and preformed mediator release. Although not the only events in coupled mast cell activation--secretion, there is a sequential relationship among perturbation of IgE-Fc receptors, transmembrane activation of adenylate cyclase, elevation of cytoplasmic levels of cyclic AMP, activation of cyclic AMP-dependent protein kinase, and secretion of mast cell granules. PMID- 6256762 TI - Strains and clones of Trypanosoma cruzi can be characterized by pattern of restriction endonuclease products of kinetoplast DNA minicircles. AB - A simple method was developed for the characterization of different strains of Trypanosoma cruzi. T. cruzi stocks isolated from vectors or by hemoculture from patients with Chagas disease could be grouped in subpopulations having similar patterns of restriction endonuclease products of kinetoplast DNA minicircles. We designate such subpopulations by the term "schizodemes." Furthermore, it is shown that, from a given T. cruzi strain, clones with different biological properties can be isolated and identified by their restriction patterns. PMID- 6256763 TI - T-cell lines established from human T-lymphocytic neoplasias by direct response to T-cell growth factor. AB - Long-term growth of lymphoblastoid T cells from tissue samples from six of six patients with cutaneous T-cell lymphoma (CTCL) and six of six patients with acute T-lymphoblastic leukemia (ALL) has been achieved by using partially purified mitogen-free human T-cell growth factor (pp-TCGF). One cell line, CTCL-2, is now independent of added growth factor; the others continue to show absolute dependency on its presence. All lines have been in continuous culture for at least 4 months and some for > 1 year. They are erythrocyte-rosette positive and are negative for Epstein-Barr virus nuclear antigen. Most of the lines are negative for Fc and complement receptors and for surface immunoglobulin except that CTCL-1 and CTCL-2 have some cells positive for these cell surface markers. Results of histochemical studies on these cell lines are similar to the known patterns for fresh cells from their disease of origin. Cell line CTCL-3 has an abnormal karyotype, but no detectable chromosomal abnormalities were found in the other lines, consistent with the karyologic features of their clinical sources. Because T cells from normal donors do not respond to pp-TCGF unless the cells are first "activated" by a lectin mitogen such as phytohemagglutinin or an antigen, the direct response to pp-TCGF of T cells from patients with T-cell neoplasias suggests that the cell lines represent a transformed neoplastic cell population. Although some of the cell lines may be normal T cells activated by the malignant cells, the morphologic and histochemical properties of the cell lines, the abnormal karyotype of CTCL-3, and the independent growth of CTCL-2 support the conclusion that most of these cell lines are of malignant origin. PMID- 6256764 TI - Nucleic acid spot hybridization: rapid quantitative screening of lymphoid cell lines for Epstein-Barr viral DNA. AB - A simple nucleic acid hybridization method to screen numerous samples of eukaryotic cells rapidly for their Epstein-Barr virus (EBV) DNA content is described. Whole cells are spotted on nitrocellulose filters and their DNA is denatured and fixed to the filter. The resultant DNA spots are hybridized to nick translated EBV DNA and the extent of hybridization is monitored by autoradiography and scintillation counting. Statistical analysis of serial dilutions of cells permits their viral genome content to be estimated quantitatively by reference to a known standard, such as Raji cells or an artificial mixture of pure viral DNA and uninfected lymphocytes. The sensitivity of the method is between 5 and 50 pg of viral DNA. With this method we are able to select subclones that are high produces of EBV DNA and to identify the optimal time for harvest of EBV DNA from cultured cells. Spot hybridization should permit any cell population or fluid to be screened for the presence of a DNA sequence for which a radioisotopically labeled probe is available. PMID- 6256765 TI - Deoxycytidine kinase-mediated toxicity of deoxyadenosine analogs toward malignant human lymphoblasts in vitro and toward murine L1210 leukemia in vivo. AB - An inherited deficiency of adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4) produces selective lymphopenia and immunodeficiency disease in humans. Previous experiments have suggested that lymphospecific toxicity in this condition might result from the selective accumulation of toxic deoxyadenosine nucleotides by lymphocytes with high deoxycytidine kinase, levels and low deoxynucleotide dephosphorylating activity. The present experiments were designed to determine if deoxyadenosine analogs which are not substrates for adenosine deaminase might similarly be toxic toward lymphocytes and lymphoid tumors. Two such compounds, 2-chlorodeoxyadenosine and 2-fluorodeoxyadenosine, at concentrations of 3 nM and 0.15 microM, respectively, inhibited by 50% the growth of human CCRF-CEM malignant lymphoblasts in vitro. Each was phosphorylated in intact cells by deoxycytidine kinase accumulated as the nucleoside triphosphate, and inhibited DNA synthesis more than RNA synthesis. Both deoxynucleosides had significant chemotherapeutic activity against lymphoid leukemia L1210 in mice. PMID- 6256766 TI - DNA gyrase on the bacterial chromosome: possibility of two levels of action. AB - In previous studies we have shown that oxolinic acid, a specific inhibitor of the A subunit of DNA gyrase, induces DNA cleavage at 100,000-base-pair intervals on the Escherichia coli chromosome. At subsaturating drug concentrations, cleavage is induced at a fraction of these sites and DNA synthesis is partially inhibited. This partial inhibition is surprisingly rapid even when few sites have been inactivated. We now report kinetic measurements suggesting that inactivation of 100,000-base-pair gyrase sites by oxolinic acid does not inhibit DNA synthesis by simply producing barriers to replication fork movement. Slowing the rate of fork movement, thus increasing the time for a fork to reach a barrier, fails to proportionately slow inhibition of DNA synthesis. Moreover, the initial, rapid phase of inhibition is followed by a slower decline that is not accelerated by increasing the frequency of barriers by raising drug concentrations. These data, when added to the observation that additional oxolinic acid-induced cleavage occurs in replicating regions of the chromosome, suggest that gyrase may function at replication forks as well as at 100,000-base-pair intervals on the chromosome. PMID- 6256767 TI - Molecular characterization, reconstitution, and "transport-specific fractionation" of the saxitoxin binding protein/Na+ gate of mammalian brain. AB - The saxitoxin (STX) binding protein has been solubilized by sodium cholate, both from axolemma and from synaptosomal membranes of mammalian brain. On the basis of agarose gel filtration and sedimentation properties in H2O and 2H2O, the solubilized particle has the following molecular properties: Stokes radius, 120 A; partial specific volume, 0.85 cm3/g; mass, 1,020,000 daltons; frictional ratio f/fo, 1.6. The solubilized STX binding protein was incorporated into unilamellar (approximately 550-A) artificial phosphatidylcholine vesicles. Based on the expectation that the STX binding protein contains functional monovalent cation gating activity ("action potential Na+ gate") that can be activated by veratridine and inhibited by tetrodotoxin, a strategy was devised for partial purification of the reconstituted sodium gate/STX binding protein by "transport specific fractionation." When the entire vesicle population was preloaded with 0.4 M cesium ion, addition of veratridine allowed Cs+ efflux from specifically those vesicles containing the ion gate; the concomitant reduction in intravesicular density permitted the ion gate/STX binding protein to be fractionated on density gradients. These observations demonstrate functional reconstitution and partial (30- to 50-fold) purification of the STX binding protein/Na+ gate of mammalian brain. PMID- 6256768 TI - Biochemical characterization of putative central purinergic receptors by using 2 chloro[3H]adenosine, a stable analog of adenosine. AB - After pretreatment of rat brain synaptic membranes with adenosine deaminase to remove endogenous adenosine, 2-chloro[3H]adenosine, a stable analog of adenosine, binds to two sites with Kd values of 1.3 and 16 nM and corresponding Bmax values of 207 and 380 fmol/mg of protein. Binding is reversible, and the highest density of sites occurs in enriched synaptosomal fractions. In peripheral tissue, negligible binding is observed in heart, kidney, and liver, while testicle has 11 fmol of binding sites/mg of protein. In brain, caudate and hippocampus have the highest density of sites, and spinal cord and hypothalamus have the lowest. This high-affinity binding is stereospecific; the L diasteromer of N6 phenylisopropyladenosine is approximately 30-times more potent as a displacer of 2-chloro[3H]adenosine than the D isomer and is also sensitive to theophylline (IC50 = 8.8 microM) and other purine-related compounds. Several putative neurotransmitters, neurotransmitter antagonists, and other centrally active compounds have no effect on binding. The data are consistent with the hypothesis that 2-chloro[3H]adenosine is binding to central purinergic receptors. PMID- 6256769 TI - Involvement of calcium channels in short-term desensitization of muscarinic receptor-mediated cyclic GMP formation in mouse neuroblastoma cells. AB - Incubation of mouse neuroblastoma cells (clone N1E-115) with Mn2+ resulted in a rapid and transient increase in cyclic GMP formation. This effect appears to be due to an increase in calcium influx because it did not occur in the absence of extracellular calcium or in the presence of verapamil, a calcium transport inhibitor. In addition, Mn2+ inhibited muscarinic receptor-mediated cyclic GMP responses. The ability of Mn2+ to increase cyclic GMP levels was markedly diminished in cells desensitized to the effects of carbamoylcholine, suggesting that this densensitization involves inactivation of calcium entry. PMID- 6256770 TI - Mechanism of calcium current modulation underlying presynaptic facilitation and behavioral sensitization in Aplysia. AB - Behavioral sensitization of the gill-withdrawal reflex of Aplysia is caused by presynaptic facilitation at the synapses of the mechanoreceptor sensory neurons of the reflex onto the motor neurons and interneurons. The presynaptic facilitation has been shown to be simulated by serotonin (the putative presynaptic facilitatory transmitter) and by cyclic AMP and to be accompanied by an increase in the Ca2+ current of sensory neuron cell bodies exposed to tetraethylammonium. This increase in the Ca2+ current could result from either a direct action on the Ca2+ channel or an action on an opposing K+ current. Here we report voltage clamp experiments which indicate that the increase in Ca2+ current associated with presynaptic facilitation results from a decrease in a K+ current. Stimulation of the connective (the pathway that mediates sensitization) or application of serotonin causes a decrease in a voltage-sensitive, steady-state outward current measured under voltage clamp as well as an increase in the transient net inward and a decrease in the transient outward currents elicited by brief depolarizing command steps. The reversal potential of the steady-state synaptic current is sensitive to extracellular K+ concentration, and both the steady-state synaptic current and the changes in the transient currents are blocked by K+ current blocking agents and by washout of K+. These results suggest that serotonin and the natural transmitter released by connective stimulation act to decrease a voltage-sensitive K+ current. The decrease in K+ current prolongs the action potential, and this in turn increases the duration of the inward Ca2+ current and thereby enhances transmitter release. PMID- 6256771 TI - Distinct cholecystokinin receptors in brain and pancreas. AB - 125I-Labeled (Bolton-Hunter) cholecystokinin triacontatriapeptide (CCK-33) binds saturably and reversibly to distinct receptors in brain and pancreatic membranes. The peptide specificity of pancreatic CCK binding is the same as that for pancreatic amylase release. In brain, gastrin and pentagastrin display nanomolar affinity for binding sites, whereas in pancreas these two peptides are virtually inactive. Though these differences indicate that brain and pancreas possess distinct CCK receptors, the two tissues show some similarities. Both pancreas and brain receptors show greater sensitivity to sulfated than to desulfated COOH terminal octapeptide of CCK and display dissociation constants of 0.3-9.5 nM. The pancreas possesses about 300 times more binding sites than does brain. CCK binding in both brain and pancreas is enhanced by divalent cations and reduced by monovalent cations. Receptor binding in both tissues is regulated in a selective fashion by guanyl nucleotides. PMID- 6256773 TI - Electron diffraction and membrane proteins. PMID- 6256772 TI - Single channel currents from excised patches of muscle membrane. AB - The currents through single acetylcholine-activated channels were measured on membrane fragments that had been torn from rat muscle myotubes with patch pipettes. The membrane fragments were sealed into the pipette by using the "gigohm-seal" technique of Neher, which also permitted voltage clamp of the membrane via the patch electrode. Membrane patches were excited by sudden withdrawal of the electrode from the cell. Substitution of fluoride for chloride ions in the bathing solution could prevent or reverse the tendency for the membrane at the electrode tip to seal over into a closed vesicle. The single membrane layer at the electrode tip could remain functional for up to 30 min. The apparent single channel conductance was minimally affected by excision. The current-voltage relationships for the single channel currents show that the inside (i.e., cytoplasmic surface) of the membrane fragment was exposed to the bathing solution. In symmetric Na solutions the current-voltage curve was nearly linear and reversed at approximately 0 mV. In other bathing solutions from 40 to 500 mM NaF, the observed zero current potential was close to that predicted by the Nernst equation. We present evidence that internal Na interacts with the channel, causing both saturation of outward current and block of inward current. At + 100 mV the apparent dissociation constant for internal Na was 138 mM. PMID- 6256774 TI - Transforming gene product of avian sarcoma viruses and its homolog in uninfected cells. AB - The product of the avian sarcoma virus (ASV) transforming gene is a 60,000-dalton phosphoprotein, pp60src. Sera from mice and from an occasional rabbit bearing ASV induced tumors are capable of immunoprecipitating a phosphoprotein of similar, but not identical, structure from normal avian and mammalian cells. This protein is presumed to be the product of the cellular sarc gene, and has been tentatively designated pp60sarc. Analysis of the tryptic phosphopeptides reveals that the viral and avian proteins have an apparently identical phosphoserine-containing peptide. They evidently also both have an analogous phosphothreonine residue surrounded by a different amino acid sequence. Immunoprecipitates containing either the viral or normal cellular pp60 protein catalyze the transfer of radiolabeled phosphate from [gamma-32P]-ATP to the heavy chain of immune rabbit IgG, therefore suggesting that both viral and cellular phosphoproteins may be protein kinases. PMID- 6256775 TI - Gene expression of Abelson murine leukemia virus. AB - Abelson murine leukemia virus (A-MuLV) represents a simple genetic system with which to study genes capable of transforming specific lymphoid target cells. A MuLV encodes a single known protein of 120,000 molecular weight (P120). A portion of this molecule is expressed at the cell surface but its function is not known. Serological reagents specific for P120 can be produced in mice regressing A-MuLV syngeneic tumors. Such sera identify a protein in normal mouse lymphoid tissues which may represent the cellular gene from which A-MuLV was derived. PMID- 6256776 TI - On the biochemistry of transformation by Rous sarcoma virus. PMID- 6256777 TI - Plasminogen activator and the membrane of transformed cells. AB - Studies have been conducted on the enzyme plasminogen activator (PA) in cultures of RSV transformed CEF. The enzyme exists in two forms, a soluble extracellular form (PAex) and a cell-associated form that is firmly bound to specific membranes (PAmem) when cell homogenates are subfractionated. Both forms of the enzyme are induced in a synergistic fashion by treatment of RSVCEF with the tumor promoter phorbol myristate acetate (PMA). The induction of the enzyme by PMA has allowed for the purification of PAex. In addition, PMA treatment of RSVCEF causes pronounced morphological alterations in culture. The use of protease inhibitors, [3H]-DFP, and a direct fluorometric assay for PA indicate that the morphological changes are due to the direct catalytic action of PA, independent of plasminogen, until now its only known natural substrate. Recent experiments suggest that PAmem is responsible for the morphological changes and that residual amounts of LETS protein are lost from the cell surface and substratum coincident with the morphological changes. The possible role of serine proteases in regulatory cellular behavior in transformed or tumor promoter-treated cells is discussed. PMID- 6256778 TI - [Preservation in aqueous solution of vancomycin, neomycin and polymyxin B, alone or in combination. Statistical analysis of antibacterial activity according to the Pharmacopee Helvetique VI]. PMID- 6256780 TI - Comparison of NMR water proton T1 relaxation times of rabbit tissues at 24 MHz and 2.5 MHz. PMID- 6256781 TI - Stopping powers of a tissue-equivalent gas for 40--200 keV protons. AB - The stopping powers of a tissue-equivalent gas were measured for protons using the proton beam from a Cockcroft and Walton type accelerator and a differentially pumped gas cell. The stopping powers of each component of the tissue-equivalent gas were also measured and used to calculate expected values of the stopping powers of the tissue-equivalent gas. Results from direct measurement and from calculation showed good agreement. The results of the measurements on the component gases were also used to calculate the stopping power of Rossi's gas. PMID- 6256779 TI - [The absorption of homologous alkyl sulphonates of tridihexethyl (author's transl)]. AB - The pharmaceutical-technological measure of varied salt formation acts on the in vivo diffusion processes of quaternary tridihexethyl (gastro-intestinal absorption, transperitoneal diffusion) in principle in the same manner as it acts on the in vitro diffusion processes (membrane diffusion): Due to the formation of corresponding ion pairs, lipophilic counterions of opposite sign facilitate the passage through membranes. In contrast, the direct pharmacodynamic activity (spasmolysis at the isolated jejunum of the rat) is not changed by varying the counterions of opposite sign. PMID- 6256782 TI - Neutron beams from protons on beryllium. AB - Measurements of dose rate and penetration in water have been made for neutron beams produced by 30--75 MeV protons on beryllium. The effects of Polythene filters added on the target side of the collimator have also been studied. A neutron beam comparable with a photon beam from a 4--8 MeV linear accelerator can be produced with p/Be neutrons plus 5 cm Polythene filtrations, with protons in the range 50--75 MeV. This is a more economical method than use of the d/Be reaction. PMID- 6256783 TI - Computer calculation of the dose distribution in the electron build-up region. AB - A procedure has been developed for producing accurate computer-calculated dose distributions at the air-tissue boundaries for oblique incidence of a photon beam. Measurements of the dose distribution under conditions of tangential incidence are presented for a Siemens 6 MV linear accelerator. These measurements have been compared with calculated distributions using the standard Cunningham Clarkson calculation technique. Based on this comparison, two changes are suggested for improving the accuracy of the calculation. The grid spacing for the calculation is decreased in order that the rapid dose variations that occur at the boundary may be better followed. Furthermore, the dose calculation scheme is modified to take into account the differences in the amount of electron build-up which occurs. An algorithm is presented for making this modification. Also, the calculated dose at the exit surface had to be modified to handle the deficit of scatter material behind the calculation points. The results of these changes are shown as a comparison of a typical chest wall irradiation treatment plan using two opposing tangential fields. PMID- 6256784 TI - The primary processes of vision: a view from the experimental side. PMID- 6256785 TI - Biochemical steps in visual transduction: roles for nucleotides and calcium ions. PMID- 6256786 TI - Rhodopsin regeneration, calcium, and the control of the dark current in vertebrate rods. PMID- 6256787 TI - Collagenase activity in human synovial fluids from joint diseases of diverse etiology. AB - The content of collagenase in latent as well as in apparent active form has been determined in synovial fluids from 21 patients with rheumatoid arthritis, 16 with non-rheumatoid inflammatory joint diseases, and 15 with degenerative joint disease. Collagenase activity was measured before and after activation of the latent enzyme by NaSCN treatment. Before activation, collagenase activity was present in the synovial fluids from 1 case of rheumatoid arthritis, 3 cases of degenerative joint disease, and 1 case of Behcet's syndrome. An excess of inhibitor was present in inactive synovial fluids. The incidence of collagenolytic activity markedly increased after treatment with NaSCN. When NaSCN dependent collagenolytic activity was present, its value was of the same order of magnitude in all patients regardless of disease type. The diagnostic value of the finding of collagenase activity in synovial fluid, and the physiological meaning of the enzyme with reference to joint diseases, are discussed. PMID- 6256788 TI - An evaluation of the selectivity of fenmetozole (DH-524) reversal of ethanol induced changes in central nervous system function. AB - The selectivity and specificity of fenmetozole (DH-524) [2(3,4-dichlorophenoxy methyl)2-imidazole HCl] as an antagonist of the actions of ethanol were examined. Fenmetozole (15--30 g/kg) reduced ethanol-induced impairment of the aerial righting reflex without changing blood or brain ethanol content, indicating that the antagonistic actions of fenmetozole were not de to change in the pharmacokinetics of ethanol. Since fenmetozole also reduced aerial righting reflex impairment due to phenobarbital, chlordiazepoxide, and halothane, this action of fenmetozole was not specific to ethanol. In mice, both the ethanol induced increase in locomotor activity at 2.0 g/kg and the decrease caused by 4.0 g/kg were antagonized by fenmetozole. In addition, fenmetozole attenuated the ethanol-induced reduction in cerebellar cyclic guanosine monophosphate (cGMP) content, but the drug also significantly elevated cGMP levels in this tissue when given alone. Fenmetozole did not alter ethanol-induced increases in punished drinking in a conflict test, except at a high dose which alone decreased both punished and unpunished responding. Fenmetozole also failed to precipitate ethanol withdrawal-like reactions when given to physically-dependent, intoxicated rats. Thus, the antagonistic action of fenmetozole against ethanol would not seem to be related to a specific receptor interaction but rather may be the result of a physiological antagonism. PMID- 6256790 TI - Effect of delta 9-tetrahydrocannabinol on the morphine-induced hyperactivity of mice. AB - The effect of delta 9-tetrahydrocannabinol (THC) on the locomotor activity stimulating action of morphine has been investigated in mice. THC (10 mg/kg) has been found to potentiate morphine-induced hyperactivity. On the other hand, the stimulating action of morphine on motor activity strongly diminished in mice rendered tolerant by the implantation of a morphine pellet. The pretreatment of morphine-tolerant mice with the same dose of THC did not change the effect of morphine on the motor activity. These results suggest that tolerance also developed to the potentiating action of THC on morphine-induced hyperactivity during the development of tolerance to this action of morphine. PMID- 6256789 TI - Importance of the Locus coeruleus and involvement of alpha-adrenergic receptors in the post-decapitation reflex in the rat. AB - The latency, duration, hindlimb kick frequency, and total activity components of the post-decapitation reflex (PDR) were measured in the rat using a movement sensitive transducer. Reduction of brain and spinal cord norepinephrine (NE) caused by neonatal administration of 6-hydroxydopamine (6-OHDA) or 5,7 dihydroxytryptamine, which also reduced brain serotonin, decreased all components of the PDR. Depletion of serotonin or dopamine alone reduced the vigor of the reflex, suggesting that these pathways can influence the PDR but are not essential for the response. Lesions of neurons in the Locus coeruleus, made electrolytically or with 6-OHDA, decreased the intensity of the PDR, with the 6 OHDA-induced lesion being more effective. Depletion of forebrain NE terminals with 6-OHDA did not alter the PDR, consistent with a critical involvement of spinal noradrenergic fibers. The PDR was also decreased by phentolamine and prazosin, but not by propanolol, suggesting an involvement of alpha-adrenergic receptors in the response. This hypothesis was further supported by the finding that the efficacy of a variety of drugs (such as tricyclic antidepressants, phenothiazines, and anti-hypertensive compounds) for blocking the reflex was apparently related to their affinity for alpha-adrenergic receptors. Thus, the PDR is dependent on noradrenergic fibers in the spinal cord and may provide a simple screen for drugs with suspected alpha-adrenergic blocking properties or for agents that disrupt the function of central noradrenergic fibers. PMID- 6256791 TI - Retrograde enhancement of human memory with alcohol. AB - In two experiments with normal male subjects, the ingestion of alcohol (1 ml/kg) immediately after learning significantly improved subsequent remembering. By comparison, marijuana (15 mg) had no significant post-acquisition effect. Facilitation of visual and verbal memory with alcohol under these conditions has implications for the interference and consolidation views of memory. PMID- 6256792 TI - Effects of an ACTH 4--9 related peptide upon intracranial self stimulation and general activity in the rat. AB - Adult male Sprague-Dawley rats were stereotactically implanted with electrodes within the anterior medial forebrain bundle. The rats were trained to respond for intracranial self-stimulation (ICS) and treated with control solution or varying doses of an ACTH 4--9 related synthetic peptide (Org 2766; H-Met(O2)-Glu-His-Phe D-Lys-Phe-OH). The drug affected ICS as measured in overnight response records, with the highest dose reliably increasing the amount of responding. In a second experiment rats were similarly treated and general activity was assessed. No remarkable changes in activity were present at any tested dose. The findings corroborate previous reports suggesting ACTH-related peptides may be active in a variety of motivated tasks, but less active with respect to general activity. PMID- 6256793 TI - Y-maze behavior after an analog of ACTH 4--9, evidence for an attentional alteration. AB - Adult, male, Swiss-Webster mice were injected with either control solution or various doses of a long-acting analog of ACTH 4--9. The drug produced significant alterations in performance in an equiangular Y-maze. In comparison with control performance, both 25 and 50 micrograms/kg of drug produced a significant increase in repeated two-arm entries. This response pattern is consistent with the hypothesis that the drug produced a focusing of attention. PMID- 6256795 TI - Acute and chronic effects of delta 9-tetrahydrocannabinol on complex behavior of squirrel monkeys. AB - Squirrel monkeys were trained to press either two (phase one) or five (phase two) differently colored keys sequentially. Food presentation resulted if colors were pressed in a specific order, and high levels or accuracy were generated. Acutely, delta 9-tetrahydrocannabinol reduced accuracy and rate of responding in a dose related fashion under both the two-key and five-key conditions. Responding, however, was more sensitive to the drug under the five-key procedure. Accuracy of responding at the beginning of a sequence tended to be more sensitive to drug effects than responding near the end. Daily (chronic) administration resulted in the development of tolerance to both the rate- and accuracy-reducing effects of the drug, although tolerance developed more rapidly to the accuracy-reducing effects. Tolerance developed more slowly under the five-key procedure than under the two-key procedure. Details of tolerance development were related to aspects of acute effects, suggesting that some facets of tolerance development may be predictable from acute drug effects. PMID- 6256794 TI - Central pharmacological control of corticosterone secretion in the intact rat. Demonstration of cholinergic and serotoninergic facilitatory and alpha-adrenergic inhibitory mechanisms. AB - A method is described for demonstrating the hypothalamic control of corticosterone in the intact rat. Oxotremorine 0.01--0.05 mg/kg IP and 5-hydroxy L-tryptophan 1--50 mg/kg IP raise plasma corticosterone levels in dose-related fashion. The oxotremorine response is blocked by atropine 1 mg/kg SC and the 5 hydroxy-L-tryptophan response by mianserin 10 mg/kg IP. alpha-Methylparatyrosine methyl ester 400 mg/kg IP raises plasma corticosterone levels 14--16 h later. This rise can be suppressed by clonidine 0.01--0.05 mg/kg IP and this suppression is antagonized by piperoxane 5--50 mg/kg IP. Apomorphine 5 mg/kg IP does not lower plasma corticosterone levels in rats pre-tested with alpha methylparatyrosine. The response to oxotremorine cannot be blocked by atropine methylbromide or by mianserin. The response to 5-hydroxy-L-tryptophan is unaffected by benserazide or atropine sulphate. These data suggest separate cholinergic and serotoninergic facilitation of corticosterone release in the intact rat. The stimulating drugs used appear to be acting centrally. The data also support the presence of a noradrenergic inhibitory system mediated by alpha adrenoceptors. Dopaminergic receptors appear to play no part in the central control of corticosterone secretion after pre-treatment with alpha methylparatyrosine. PMID- 6256797 TI - The coupling of receptors to adenylate cyclases [proceedings]. PMID- 6256796 TI - delta 9-THC as a discriminative stimulus in rats and pigeons: generalization to THC metabolites and SP-111. AB - In a drug discrimination paradigm pigeons and rats were trained with an operant procedure to discriminate between the presence and absence of the effects of delta 9-THC (1.0 and 3.0 mg/kg, injected IM 90 min and I.P. 30 min before the start of the session). Once trained, various THC metabolites as well as a water soluble derivative of THC (SP-111), were substituted for delta 9-THC to test for generalization to the training drug. Generalization to delta 9-THC occurred with the 11-hydroxy metabolites and the potency order was 11-OH-delta 9-THC > 11-OH delta 8-THC greater than or equal to delta 9-THC. Among the other metabolites tested (8 alpha-OH-delta 9-THC, 8 alpha, 11-di-OH-delta 9-THC, 8 beta-OH-delta 9 THC, 8 beta, 11-di-OH-delta 9-THC), it was only 11-di-OH-delta 9-THC that completely substituted for delta 9-THC in pigeons, albeit at very high dose levels (rats were not tested with these metabolites). SP-111 generalized to delta 9-THC in both species. However, the onset of action of SP-111 was slower than that for delta 9-THC, especially in pigeons. These studies show the importance of obtaining complete dose-effect determinations over time when assessing structure activity relationships with drug-discrimination procedures. PMID- 6256799 TI - ADAMHA's mission of prevention. PMID- 6256798 TI - Protein fluctuations and time-space asymmetries in brain [proceedings]. PMID- 6256800 TI - [Nerve injuries]. PMID- 6256801 TI - Effects of pulsed electric fields on rat liver homogenate paramagnetic species. AB - Rat liver homogenate has been submitted to pulsed electric fields at different intensities and exposition times. Among the paramagnetic species present in the samples only the mitochondria free radical is affected by pulsation, as revealed by electron spin resonance spectroscopy. In parallel a variation in the respiratory activity of mitochondria is registered. PMID- 6256803 TI - Radiation damage to nucleosides and nucleotides. III. AC4'-centered radical in the ribose moiety of uridine-5'-phosphate single crystals. PMID- 6256802 TI - Effects of 1.9 MeV monoenergetic neutrons on Vicia faba chromosomes: microdosimetric considerations. AB - Aerated Vicia faba root meristems were irradiated with 1.9 MeV monoenergetic neutrons. This source of neutrons optimally provides one class of particles (recoil protons) with ranges able to traverse cell nuclei at moderate to high LET. The volumes of the Vicia faba nuclei were log-normally distributed with a mean of 1100 micrometer3. The yield of chromatid-type aberrations was linear against absorbed dose and near-constant over 5 collection periods (2-12 h), after irradiation. Energy deposition events (recoil protons) determined by microdosimetry were related to cytological changes with the finding that 19% of incident recoil protons initiate visible changes in Vicia faba chromosomes. It is probable that a substantial fraction of recoil proton track length and deposited energy is in insensitive (non-DNA containing) portions of the nuclear volume. PMID- 6256804 TI - Potentially lethal and DNA radiation damage: similarities in inhibition of repair by medium containing D2O and by hypertonic buffer. PMID- 6256805 TI - Combined effects of anticholinesterase drugs and low-level microwave radiation. PMID- 6256806 TI - [Radiation therapy of the most frequent solid tumours in childhood (author's transl)]. PMID- 6256807 TI - [Labelling index of pulmonary carzinoma cells following preoperative irradiation with high single doses (author's transl)]. PMID- 6256808 TI - Infarct avid (hot spot) myocardial scintigraphy. AB - Infarct avid scintigraphy has emerged as a noninvasive method for determining the presence, location, and extent of myocardial necrosis secondary to infarction. In the future, it may replace studies such as serum enzyme tests, electrocardiography, and vector cardiography, all of which provide only indirect evidence of these parameters. PMID- 6256809 TI - [Angioscintigraphic examinations of pancreatic tumours (author's transl)]. PMID- 6256810 TI - The ultrasonographic appearance of cystic hepatoblastoma. AB - Cystic hepatoblastomas share ultrasonographic characteristics with simple hepatic cysts; however, a distinction can be made by the demonstration of internal septations. The differentiation is important because cystic hepatoblastoma may have malignant potential. The ultrasonographic and scintigraphic findings in five children with cystic hepatoblastoma are reviewed. PMID- 6256811 TI - The value of abdominal computed tomography in the pre-treatment assessment of small cell carcinoma of the lung. AB - Computed tomographic (CT) scans of the abdomen were obtained in 65 patients with biopsy-proved but untreated small cell carcinoma of the lung. Intra-abdominal metastases were found in 24 (37%), the majority being in the liver and adrenals. Abdominal CT before treatment is recommended as a part of the staging process in patients with small cell carcinoma of the lung, since extent of disease is relevant to prognosis. PMID- 6256813 TI - ACTH-like peptides, pituitary-adrenocortical function and avoidance behavior. PMID- 6256812 TI - Residual radiation damage in the mouse foot after exposure to heavy particles. AB - Mice receiving a first treatment with graded doses of various heavy charged particles (protons and heavy ions) to one of their hind legs were re-exposed to a fixed dose of x rays eight months later to study the "memory" of residual damage from the first treatment. No significant memory of the first radiation exposure was observed for acute skin rection. However, there is an indication of memory for foot deformity. The results do not seem to indicate any significant differences in memory after exposure to 60Co gamma rays compared with protons or heavy ions, if biological effectiveness of the doses is taken into consideration. PMID- 6256814 TI - Influences of stress-related hormones on a variety of models of attack behaviour in laboratory mice. PMID- 6256815 TI - The interaction of experience and neuroendocrine factors in determining behavioral adaptations to aggression. PMID- 6256816 TI - Relationships between structure and function of convulsant drugs. PMID- 6256817 TI - Noise analysis and channels at the postsynaptic membrane of skeletal muscle. PMID- 6256818 TI - Cardiovascular effects of linoleic acid. PMID- 6256819 TI - Effects of saturated and polyunsaturated fat diets on the chemical and physical properties of lipoproteins from type V hyperlipoproteinemic subjects. PMID- 6256820 TI - Influence of fatty acid composition of membrane phospholipids on membrane-bound enzymic activities. PMID- 6256822 TI - Replicative DNA polymerases and mechanisms at a replication fork. PMID- 6256824 TI - [Angiographic follow-up of abdominal tumours in children following radio and chemotherapy (author's transl)]. AB - The authors report 13 cases of pediatric abdominal tumours (1 hepatoblastoma, 8 neuroblastomas, 4 Wilms' tumours) angiographically evaluated following radiation and chemotherapy. The results suggest possible indications for radical surgery, in patients previously considered inoperable. PMID- 6256823 TI - [Contrast media in use in myelography and ventriculography: current status and future prospects]. PMID- 6256821 TI - Structure of transcribing chromatin. PMID- 6256825 TI - [Biosynthesis of polypeptide hormones]. AB - The biosynthesis of numerous polypeptide hormones implicates two types of precursors: pre- and prohormones. The structure, characteristics, and role of these hormone precursors is discussed taking as examples parathyroid hormone and insulin. After this general introduction, the case of the common precursor for adrenocorticotropin and beta-lipotropin is then discussed. Its maturation proceeds through a serie of proteolytic steps which lead to the formation of various end products characterized each by a biological activity of its own. PMID- 6256826 TI - [Main respiratory virus and Chlamydia psittaci antibody survey by passive hemagglutination on bovine serum from Togo]. PMID- 6256827 TI - [The reproduction of stationary bovine livestock on the North Ivory Coast : the use of calving intervals; methodological aspects and first results]. PMID- 6256828 TI - [A rare procedure: angiofibroma of the nasal cavity]. PMID- 6256829 TI - [Value of the determination of carcinoembryonic antigen (CEA) in benign and tumoral digestive pathology, chronic hepathopathies and hepatomas: study of 190 cases]. PMID- 6256830 TI - [Cyclic AMP. Physiopathological and clinical aspects]. PMID- 6256831 TI - [Cyclic AMP and essential arterial hypertension. Role of the adrenergic system]. PMID- 6256832 TI - [Epstein-Barr virus and human cancer]. PMID- 6256833 TI - [Current status of autoimmune thyroid diseases]. PMID- 6256834 TI - [Interrelations among prostaglandins, cyclic AMP and calcium ions in regulation of the inflammatory process]. PMID- 6256835 TI - Brain, behavior, and bodily disease. Introduction: the role of the brain in bodily disease. PMID- 6256836 TI - Psychosocial stimuli, physiological specificity, and cardiovascular disease. PMID- 6256837 TI - The hypothalamus and the immune response. PMID- 6256838 TI - Differentiation of porcine enterovirus serotypes by complement fixation. AB - A complement fixation test in microtitre plates for the differentiation of porcine enterovirus serotypes is described, employing guinea pig antisera prepared using inactivated purified viruses. Eleven porcine enterovirus serotypes and swine vesicular disease virus were compared and clearly distinguished from each other. In addition, 71 porcine enterovirus strains and isolates were tested and each was identified as belonging to one of the 11 serotypes. PMID- 6256839 TI - Cerebral resistance to anoxia in the marine turtle. AB - The extraordinary ability of the turtle to withstand prolonged anoxia was examined in cerebral cortex in situ by recording changes in the reduction/oxidation ratio of cytochrome a,a3 by reflection spectrophotometry. Inspiration of 100% oxygen increased the oxidation of cytochrome a,a3 beyond that of the air breathing control, suggesting that cytochrome a,a3 is not fully oxidized under normoxic conditions in turtle brain. A similar response was seen also in cerebral cortex of the rat. The significance of the cytochrome a,a3 reduction in these intact tissues is discussed. Both severe hypoxia (100% N2) and asphyxia produced increasing levels of reduced cytochrome a,a3 in turtle and rat brains. The rat of change produced by N2 inspiration was greater than that produced by asphyxia in both species. This is interpreted as demonstrating an open pulmonary blood circulation during anoxia. In turtles, levels of reduced cytochrome a,a3 were maintained for over 3 h of continual N2 inspiration. Subsequent inspiration of room air resulted in a full restoration of turtle brain cytochrome a,a3 redox state within 30 sex. In the rat, continued N2 inspiration resulted in a rapid reduction of cytochrome a,a3 to a plateau (3 min) which became irreversible within a short period. An extended tolerance of N2 inspiration found in rats cooled to temperatures approximating that of the turtle was inadequate to account for the wide species of difference. We suggest that special adaptations, not related to the redox state of cytochrome oxidase under normoxic conditions, are responsible for maintaining the functional integrity and the capacity for cytochrome oxidase re-oxidation of turtle brain mitochondria under prolonged anoxia. PMID- 6256840 TI - [Syndactylia, polydactylia and absence of thumbs associated with tibial hypoplasia and a nose abnormality in 2 generations: a new syndrome]. PMID- 6256841 TI - [Bread]. PMID- 6256842 TI - [Scintigraphy with 99m Tc pyrophosphate in the localization of myocardial infarction. Correlation with electrocardiographic and vectorcardiographic data]. PMID- 6256843 TI - A fifteen-month study on the efficacy of a single 15 mg/kg dose of oxamniquine (Vansil) in Schistosoma mansoni in an endemic area. PMID- 6256844 TI - Circulating immune complexes in patients with lung neoplasms. AB - A search was made for circulating immune complexes in 42 patients with biopsy proven lung cancer; sex- and age-matched healthy volunteers were used as normal controls. Two different mthods were employed: Clq--binding assay and the conglutinin-binding test. Patients and controls were also examined for delayed hypersensitivity by a skin testing using a set of recall antigens. A significant difference was found in the incidence of immune complexes and the response to skin tests between neoplastic subjects and normal controls. However, the incidence of immune complexes was not related to delayed hypersensitivity or the other clinical features investigated. PMID- 6256845 TI - [Present status of neurology in 1980]. PMID- 6256847 TI - Serum levels of mecillinam in patients with severely impaired renal function. AB - 12 patients with severe renal insufficiency were treated for urinary tract infection with 400 mg of mecillinam intravenously every 6 h. High serum concentrations of mecillinam were found 6 h after the first morning dose on day 2 and day 5 of the treatment period (mean values 11.4 and 14.5 microgram/ml respectively), and a serum half-life of 334 min. In spite of reduced elimination of the drug, a nearly steady state was achieved within the first few days of treatment. Side effects were not observed. PMID- 6256846 TI - [Hyperparathyroidism secondary to cirrhosis. Arguments supplied by ionized calcium, urinary cyclic AMP and blood N-terminal parathyroid hormone]. AB - A laboratory study including estimation of 25 OH vitamin D, terminal parathormone (PTH) C and N fractions, urinary cyclic AMP (AMP cU) and ionised calcium, was carried out in 25 patients, 10 cases of alcoholic cirrhosis without decompensation (group 1) and 15 cases of decompensated cirrhosis (group 2) in order to seek evidence in favour of hyperparathyroidism secondary to cirrhosis. The results show: 1) The existence of hypovitaminosis D which seems to be independent of the liver failure. 2) A very definite increase in terminal PTH N in group 2 compared with group 1 (p < 0.01), without any increase in terminal C fraction. 3) An insignificant increase in urinary cyclic AMP in group 2 compared with group 1. 4) A low serum ionised calcium in group 2 compared with 14 controls (p < 0.05). The terminal N PTH was correlated significantly with urinary cyclic AMP and ionised calcium. The evidence is in favour of secondary hyperparathyroidism where the ionised calcium plays a role, but one wonders whether other factors do not intervene, e.g. serum iron, owing to the discovery of a significant link between serum iron and terminal N PTH levels. PMID- 6256848 TI - The effect of penicillamine and 2,3-dimercaptosuccinic acid on urinary excretion and tissue distribution of gold. AB - In order to study interactions in vivo between Au+ and SH-containing agents, groups of mice were given 35 mumol/kg of radiolabelled [195Au] thiomalate (Myocrisin) intramuscularly. The administration of Myocrisin is known to result in protein-bound gold and free thiomalate (mercaptosuccinate). High doses of dimercaptosuccinate (1 mmol/kg daily) increased the urinary excretion of radiolabelled gold [195Au] for several days. Treatment for 7 days with 1 mmol/kg of penicillamine or dimercaptosuccinate reduced the blood and kidney levels of gold to 30--50% of the controls. The oral administration of penicillamine in high doses, 1--10 mmol/kg, increased significantly the urinary excretion of [195Au] the first day after the Myocrisin injection, but on the subsequent days the radio metal excretion was unaffected by the treatment. A lower dose level of penicillamine (0.3 mmol/kg daily) gave rise to only a small and insignificant increase in the urinary excretion of gold. The present results indicate that penicillamine at low clinical doses is an inefficient chelator of gold, while high doses (presumably comparable to about 1 200 mg daily in humans) may mobilize certain amounts of the metal deposits. PMID- 6256849 TI - Experimental arthritis induced by granulocyte collagenase. AB - Purified human granulocyte collagenase (1 mg %, 10 mg % or 50 mg %) was injected into rabbit knee joints (three groups of 6 animals each) three times within one week. Synovium and synovial fluid were investigated 18 hours, 1 week and 3 weeks after the last injection. After 18 hours, synovial fluids showed distinct cellular exudation, its size depending on the amount of collagenase applied. A smaller number of cells was seen after one week, while normal cell counts were observed 3 weeks after the last injection. Histologically, synovium showed an acute arthritis after 18 hours, whereas after 1 and 3 weeks a chronic proliferative form of arthritis with predominant activation of fibroblasts was diagnosed. As compared with an experimental arthritis induced with rheumatoid synovial collagenase, granulocyte collagenase was less arthritogenic. Neither trypsin nor saline injections induced distinct cellular exudation into synovial fluids nor histologic signs of arthritis. PMID- 6256850 TI - The effect of fasting on plasma cyclic adenosine-3', 5'-monophosphate in rheumatoid arthritis. AB - Cyclic adenosine-3', 5'-monophosphate (cAMP) may influence important mechanisms in the inflammatory process, and fasting has been claimed to be clinically beneficial in rheumatoid arthritis (RA). A study was therefore designed to measure the concentrations of plasma cAMP in RA patients not undergoing drug treatment during a control and a fasting period. Twelve female RA patients were hospitalized for two 14-day periods and investigated in a crossover study. Clinical and laboratory variables of inflammatory activity were assessed during both periods. During the control period the concentrations of cAMP in plasma were slightly below the lower normal limit, with no significant change throughout the period. The clinical and laboratory variables of inflammatory activity were unchanged during the same period. In the fasting period, the prefasting level of plasma cAMP was significantly higher than on the corresponding day in the control period. During 7 days of total fasting the plasma cAMP concentrations decreased significantly. The clinical and laboratory variables of inflammatory activity decreased significantly from the start to the end of fasting. High prefasting plasma cAMP concentrations were associated with improvement in clinical inflammatory activity. A decrease in plasma cAMP concentrations during fasting in RA patients is in contrast to the findings in obese and healthy subjects previously reported. PMID- 6256851 TI - Supercoiled DNA. PMID- 6256852 TI - Ectopic hormone production by tumours. Clinical aspects. AB - The ectopic production of hormones by tumours is important to appreciate as relevant endocrine features may antedate the appearance of other evidence of the tumour. This possibility should be borne in mind particularly when considering Cushing's syndrome, excessive ADH production or hypercalcaemia and could result in many instances in a quite different approach to further investigation and management. Carcinoma of lung is the commonest underlying neoplasm in several such situations but there are some, such as the hypoglycaemic syndromes, in which the tumour may even be benign. PMID- 6256853 TI - Ectopic hormones--biochemical aspects. AB - Biochemical evidence suggests that ectopic hormone production is much more common than suspected clinically. The majority of lung carcinomas of oat cell or carcinoid type appear to synthesise ACTH and related peptides, calcitonin and less frequently, chorionic gonadotrophin and vasopressin. The primary amino acid sequences of ectopic hormones closely resemble their normal counterparts but ectopic hormone producing tumours contain greater proportions of high molecular weight, subunit and fragment forms than the normal gland of origin. Assays for ectopic hormones are clinically useful in diagnosis, tumour localisation, and monitoring patients with ectopic hormonal syndromes. Currently the clinical value of hormone assays in the routine management of common forms of malignancy in the absence of overt ectopic hormonal syndromes is unproven. However, better characterisation of hormonal forms relatively specific for neoplasia together with improved assay specificity and sensitivity may enhance the clinical value of ectopic hormones as tumour markers, particularly in malignancies which are commonly associated with ectopic hormone production (e.g. lung cancer). PMID- 6256854 TI - Mouse pox threat. AB - A News and Comment Briefing ("OSHA backs away from strict lab rules," 28 Nov. 1980, p. 992) incorrectly quoted a National Research Council report on safe handling of laboratory chemicals as saying, "For most laboratory environments, ... regular monitoring of the airborne concentrations of a variety of different toxic materials is both unjustified and unjust." The report actually said it was "unjustified and impractical." PMID- 6256855 TI - Regulation of cutaneous previtamin D3 photosynthesis in man: skin pigment is not an essential regulator. AB - When human skin was exposed to simulated solar ultraviolet radiation, epidermal 7 dehydrocholesterol was converted to previtamin D3. During prolonged exposure to simulated solar ultraviolet radiation, the synthesis of previtamin D3 reached a plateau at about 10 to 15 percent of the original 7-dehydrocholesterol content, and previtamin D3 was photoisomerized to two biologically inert isomers, lumisterol3 and tachysterol3. Increases either in skin melanin concentration or in latitude necessitated increases in the exposure time to simulated solar ultraviolet radiation required to maximize the formation, but not the total content, of previtamin D3. In order of importance, the significant determinants limiting the cutaneous production of previtamin D3 are (i) photochemical regulation, (ii) pigmentation, and (iii) latitude. PMID- 6256856 TI - Metkephamid, a systemically active analog of methionine enkephalin with potent opioid alpha-receptor activity. AB - Metkephamid is an analog of methionine enkephalin that retains high affinity for the delta receptor and is a systemically active analgesic. Since it is at least 100 times more potent than morphine as an analgesic when placed directly into the lateral ventricles, and is 30 to 100 times more potent on the delta receptor and yet is roughly equipotent on the mu receptor in vitro, it is concluded that it probably produces analgesia by action on delta receptors as well as, or rather than, on mu receptors. It has less tendency to produce respiratory depression, tolerance, and physical dependence than standard analgesics, and it is presently undergoing clinical trial. PMID- 6256857 TI - Gene expression in eukaryotes. AB - Gene expression in eukaryotes is influenced by a wide variety of mechanisms including the loss, amplification, and rearrangement of genes. Genes are differentially transcribed, and the RNA transcripts are variably utilized. Multigene families regulate the amount, the diversity, and the timing of gene expression. The present level of understanding of gene expression in eukaryotes is attributable mainly to biochemical methods rather than to traditional genetics. The new techniques that permit analysis and modification of purified genes of known function will identify both the control regions in eukaryotic genes as well as the molecules within cell that influence gene expression. PMID- 6256858 TI - Jumping genes help trace inherited diseases. PMID- 6256859 TI - Interaction between purine and benzodiazepine: Inosine reverses diazepam-induced stimulation of mouse exploratory behavior. AB - Inosine, 2-deoxyinosine, and 2-deoxyguanosine completely reversed the increase in exploratory activity elicited in mice by diazepam. The inhibition of exploratory behavior by purines occurred at doses that when given alone have no effect on exploratory behavior. 7-Methylinosine, which does not bind to the brain benzodiazepine binding site in vitro, had no effect on the diazepam-induced increase in exploratory behavior. Behavioral effects produced by various combinations of inosine and diazepam indicate that the interaction between purine and benzodiazepine is antagonistic and support the hypothesis that the naturally occurring purines function in anxiety-related behaviors that respond to benzodiazepine treatment. PMID- 6256860 TI - [Sternal plasmocytoma with monoclonal dysglobulinemia 28 months after a trauma. Pathogenic discussion (author's transl)]. AB - A case of sternal plasmocytoma discovered 28 months after an occupational trauma is reported. At the first examination a small quantity of monoclonal IgG was present, and persisted in spite of a rather heavy treatment by irradiation and chemotherapy. To-day, more than eight years after the trauma, there is not any clinical or radiological sign of generalization, but bone marrow plasmocytosis is notably increased. Thus the long-dated prognosis is reserved. We discuss the frequency of solitary plasmocytomas of the sternum, the possibility of generalization sometimes after a very long delay, the relationship between the trauma and the plasmocytoma, the lack of pejorative significance of associated monoclonal dysglobulinemia. We suppose that in our case the dysglobulinemia antedated the trauma, this hypothesis is corresponding to the present concepts on oncogenesis, the trauma being only a cocarcinogenic agent. PMID- 6256861 TI - [Polycythaemia and uterine fibroma. A case with in vitro demonstration of an erythropoietic activity in the tumor (author's transl)]. AB - A new case of polycythaemia associated with an uterine fibroma is presented. The presence of erythropoietin in the tumor has been demonstrated by an in vitro technique of titration using a microculture of foetal mouse liver cells. The study of 46 previously reported cases show that the usual pattern is that of an isolated polycythaemia occurring in a woman in her fifty and of a large fibroma. The surgical cure of the tumor relieves rapidly and definitively the polycythaemia. The hypothesis of an inappropriate secretion of erythropoietin seems admitted, three factors playing probably a role in the occurrence of the polycythaemia: size of the fibroma, state of the iron stores and presence of an inhibitory factor against erythropoiesis. PMID- 6256862 TI - [Hereditary thrombocytopenia-thrombocytopathy with myelofibrosis (author's transl)]. AB - A case of hereditary autosomal recessive thrombocytopenia is reported. Thrombocytopathy is associated with the thrombocytopenia. There is a contrast between the cytologic aspect of poor bone-marrow without any megakaryocyte and the histologic aspect of dense bone-marrow with a normal number of megakaryocytes. Myelofibrosis can explain this discrepancy. The life time of platelets being just a little shortened, the disease is probably due to a lack of bone-marrow production. PMID- 6256863 TI - [Willebrand's disease and pregnancy (author's transl)]. AB - Autosomal dominant hemorrhagic disorder, Willebrand's disease causes hemorrhagic complications during post-partum period. Nevertheless our case-report as well as others's have shown that these complications only occur when there is no spontaneous biologic improvement and can be prevented by prophylactic treatment with cryoprecipitates or anti-hemophilic A fractions. This risk requires thus a regular watch of the biologic aspects during pregnancy and before the delivery date in order to decide of a possible treatment, which will be absolutely necessary in case of obstetrical surgery. PMID- 6256864 TI - [Adult Still's disease with constrictive pericarditis, Sjogren's syndrome and varied leucocytic abnormalities (author's transl)]. AB - Adult Still's disease is a newly described disorder that is of interest not only for the rheumatologist but also for the internist since fever or extra-articular symptoms can reveal this disorder, which appears to be identical to the Wissler Fanconi's syndrome. We report a new case characterized by the occurrence of a constrictive pericarditis with clinical features of protracted fever, by the late appearance of a Sjogren's syndrome and by peculiar blood abnormalities: hyperleucocytosis up to 80 000 after splenectomy, transient Felty's syndrome, blood monocytosis and bone marrow mastocytosis. PMID- 6256865 TI - [Adult Still's disease (author's transl)]. AB - The study of 36 published cases of adult Still's disease shows the following features: the onset takes place usually during the third decade of life, most often as a polyarthralgia characterized by sometimes starting fever, evanescent rash, neutrophil leukocytosis, negativity of the serological tests for rheumatoid arthritis and systemic lupus; lymphadenopathy and splenomegaly are frequent but not constant; serous cavities, particularly pericardium, are rather frequently involved; evolution is characterized by a succession of relapses and remissions, the far prognosis being rather good (1/3 of cures, 1/3 of mild articular relapses, 1/3 of articular sequelae, involving chiefly neck and hips); corticosteroids and heavy doses of aspirin seem to give the best therapeutic results, the usefulness of a maintenance treatment is debatable. PMID- 6256866 TI - [Varicocele and male hypofertility. Report of 100 cases]. AB - 100 cases of man-hypofertility associated with a varicocele have been submitted to a varicocelectomy using Ivanissevitch's procedure. Pre-operative spermogram and spermocytogram as well as testicular biopsy proved to be of no prognostic value. The only difference between pre-operative and post-operative spermocytograms concerns sperm motility. The main prognostic factor seems to be normal findings in the gynecologic examination of the female partner. Ligation of spermatic artery appears to be associated with a higher rate of failure. PMID- 6256867 TI - [Progressive multifocal leukoencephalopathy and hemochromatosis. Pathological study of a case (author's transl)]. AB - A case of progressive multifocal leukoencephalopathy (P.M.L.) with humoral immunologic deficiency and hemochromatosis has been studied by light and electron microscopy. Widespread demyelination of white substance, gigantic astrocytes, inflammatory perivascular cuffs and numerous nuclear and cytoplasmic viral inclusions, suggesting Papovavirus were observed. The relationship between P.M.L. and hemochromatosis is discussed. PMID- 6256868 TI - [Intravenous urography after radiosurgical treatment of uterine cancer (stages T1 and T2). Normal transient features and urological complications (author's transl)]. AB - The same radiosurgical treatment was given to 108 cases of stages T1 and T2 uterine cancers, and consisted of curietherapy followed by an extended colpohysterectomy with lymph node resection (Meigs operation) Intravenous urography was performed during operation in all patients, and at least one postoperative intravenous urography was also carried out. Stricture of the pelvic ureter was discovered postoperatively in 50.9% of cases, with or without subjacent stasis: this type of image is transient and disappears within eight months. A lymphocele can cause images showing signs of bladder pressure. Ureteral and vesical complications of a true and definitive nature are extremely rare. PMID- 6256869 TI - [Hepatic lesions caused by vinyl chloride monomer in humans. Study of eight clinicopathological cases (author's transl)]. AB - Six hepatic angiosarcomas, one hepatoma and one hepatic "fibrosis" with portal hypertension in patients chronically exposed to vinyl chloride monomer (VCM) are reported. The industrial methods of synthesis and current knowledge concerning the carcinogenic role of VCM are reviewed. Histogenetic and pathogenetic concepts of "fibrosis" and angiosarcomas of liver are exposed. PMID- 6256870 TI - [Radiological aspects of pulmonary lesions due to Mycoplasma pneumoniae. A report of 70 cases (author's transl)]. AB - Radiological appearance in 70 cases of pulmonary affection due to Mycoplasma pneumoniae are described. The most frequently seen radiological images are those in which a focus of bronchopneumonia sometimes associated with areas of atelectasis is observed. Reticulonodular lesions are observed less frequently but pseudomiliary or even pseudotumoral images may be present. Pleurisy was found in 17.1% of the cases, which is contrary to the data of the published literature, but no mediastinal or hilar adenopathy was observed. The authors emphasize the frequent unilateral localization of the lesions in the lower pulmonary zone, but stress that the classical migratory character of the lesions is difficult to evaluate in an affection which often involves multiple lesions. PMID- 6256871 TI - [Hypoglycemia in a patient with chronic lymphoid leukemia (author's transl)]. AB - A case of severe hypoglycemia is reported in a 71-year-old woman suffering from chronic lymphoid leukemia for three years. Hormone analysis shows that hypoglycemia was related to a Langerhans adenocarcinoma. PMID- 6256872 TI - [Paraneoplasic acrokeratosis of Bazex (author's transl)]. AB - Acrokeratosis of Bazex is a true paraneoplasic syndrome of evocative by its acromegalic and symetric topography of erythemato-keratosic lesions. It always reveals an aerodigestive epithelioma. Its diagnosis is very useful for early treatment of the epithelioma. Its diagnosis is very useful for early treatment of the epithelioma. Its evolution is parallel with primitive cancer and is the best criteria of watching. PMID- 6256873 TI - [Bilateral lobular in situ carcinoma discovered by sub-cutaneous mastectomy (author's transl)]. AB - The authors relate the observation of a 42 years old woman with antecedents of mastodynia from several years and numerous operations for fibroadenoma. During the follow-up a sub-cutaneous mastectomy is realized owing to the discovery of clustered calcifications on mammographic study, which reveals a bilateral lobular in situ carcinoma. They talk over surgical procedures in this form of carcinoma. PMID- 6256874 TI - [About eosinophilic infiltration in cellular tissue (author's transl)]. AB - With this paper, we want to settle the part of eosinophilia in the definition of diseases as entities. Consequently, we emphasize the contribution of eosinophils in the histological diagnosis. Eosinophilic infiltration is the main marker of several lesions. We review successively some of these entities. They belong to tumoral or inflammatory (without or with vasculitis) pathology. The function of eosinophils must improve our knowledge about the significance of all these lesions (parasitic infestation, hypersensitivity...). These physiopathological mechanisms must be helpful to draw some new borders between these different entities. PMID- 6256875 TI - [Cross-over study of benfluorex and a hypolipemic agent in diet-resistant types IV and II b hyperlipemia (author's transl)]. AB - The effects of benfluorex and a hypolipemic agent were compared in 24 patients with types IV or II b hyperlipoproteinemia unimproved after 4 months diet, by means of a cross-over study with two periods of two months treatment separated by two months without treatment. Results showed similar efficacy for each treatment against lipid parameters; statistically significant variations in body weight ( 0,8%; p < 0,0001), fasting blood sugar (-11,7%; p < 0.001), and of uric acid ( 8,3%; P greater than or equal to 0,001) with benfluorex VS., respectively (-0,1%; P: NS), (+ 3,4%; P < 0.05), and (+ 1,3% PP: NS) with the hypolipemic agent; statistically significant reductions in VLDL electrophoretic levels; (29,7%: P < 0,001) with benfluorex VS., (17,3%; P < 0.001) with the hypolipemic agent; and an increase in HDL electrophoretic levels; benfluorex (10,7%; P < 0,001) VS., (0,9%; P: NS) with the hypolipemic agent. PMID- 6256876 TI - [Intrasellar chordoma (author's transl)]. AB - The authors present two cases of intrasellar chordoma and review these tumor's most important characters. This intrasellar localization seems to be very rare. Endocrinological disorders, when observed, leads only to insfufficiency and never to hypersecretion. Final diagnosis is established by histological studies. Their volume is important, so that the recurrence after surgery is common and the middle term prognosis is bad. PMID- 6256877 TI - [Sarcoidosis and angioimmunoblastic lymphadenopathy with secondary immunoblastic sarcoma (author's transl)]. AB - A case associating simultaneously a sarcoidosis and an angioimmunoblastic lymphadenopathy is reported. The disease developed into a malignant lymphoma. The immunologic features and the links between the two diseases are discussed. PMID- 6256878 TI - [Pelvic recurrence after abdomino-perineal resection for carcinoma of the rectum (author's transl)]. AB - The clinical features of pelvic recurrence in a series of 52 patients who underwent abdomino-perineal excision for carcinoma of the rectum are described. About 80% of these recurrences occurred within 2 years after surgical treatment. Low level of tumor in the rectum, local spreading into peri-rectal fat or serosa, lymph node involvement are factors related to high incidence of local recurrence. The bad prognosis of this pattern of failure leads to suggest that radiotherapy be given a trail as an adjuvant method of treatment to conventional surgical approach. PMID- 6256879 TI - [Neurological and hepatic complications in chrysotherapy (author's transl)]. AB - The authors report the case of two neurologic complications and one hepatic complication gold salt induced. They study the prevalence, the clinical features, biological data and mechanisms of these complications. PMID- 6256880 TI - [Susceptibility of anaerobic bacteria to cefoxitin (author's transl)]. AB - Nine strains of Clostridium perfringens type A and 10 strains of Bacteroides fragilis s. spec. fragilis, recently isolated from blood culture, were tested for their cefoxitin susceptibility. The MIC for Clostridium perfringens ranged from 0,6 to 5 mg/l and 1,2 to 10 mg/l for Bacteroides fragilis. In most cases, the MBC were identical with the MIC for Clostridium perfringens, but for Bact. frag. there was a difference of 2 dilutions in their MBC. Cefoxitin activity was not modified by a variation in inoculum density. PMID- 6256881 TI - [Treatment of dissecting aneurysms of renal artery. Report of four cases (author's transl)]. AB - The localized dissection of visceral arteries, renal arteries in particular, is less frequent than the extension forward the visceral arteries of aneurysms of the abdominal aorta which are well known. Reporting on four cases within their own personal experience, the authors present their commentaries and insist upon the necessity of early diagnosis which, thanks to an adapted surgical treatment, permits protection of these patients from the complications inherent in this reno vascular pathology. PMID- 6256882 TI - [Value of ultrasonography in the diagnosis of renal abscesses. Results in 13 cases (author's transl)]. AB - The results of ultrasonography recordings in 13 patients with renal abscesses are described: the image of the abscess is that of a cavity, of mixed structural composition, located inside the renal parenchyma. Ultrasonography has great diagnostic value, can be used to guide the aspiration needle and therapeutic procedures, and permits effective follow-up of the course of the disease. Chronic abscesses develop thick borders which give an ultrasonographic appearance similar to that of a necrotic cancer. In the perinephric phlegmon the cavity compresses the capsule. The pyonephrotic kidney is large and heterogenous in appearance. The clinical picture and the results of guided needle puncture are the essential features for diagnosis. PMID- 6256883 TI - [Study of 241 epitheliomas of uterine cervix (T1-T2) treated by radio-surgical procedure (author's transl)]. AB - A casuistic study of 241 epidermoid cancers of the uterine cervix treated at the Cancer Center in Nice is analysed depending upon various protocols. The cases are studied according to the stage and type of treatment, with indication of the incidence of lymph node involvement. Surgical or radiological procedure, pelvic node-vaginal recurrence, modalities of death and survival control at five years are detailed. Results reveal the advantage of a radio-surgical procedure. PMID- 6256884 TI - [Tiapride and painful attacks of drepanocytosis (author's transl)]. AB - Patients with drepanocytosis require frequent hospitalization for treatment of the severe attacks of pain induced by the disease process. Therapy is often of limited extent and vasodilators, the usual medication employed, do not give very satisfactory results. A study with tiapride demonstrated that this compound could be effective both for curative and preventive treatment, probably in relation to its direct action on pain centres. Very good results were obtained in 11 cases, good results in 8, moderate results in 2, and no result in one case only. PMID- 6256885 TI - [Benign tumours of the liver and oral contraceptives (author's transl)]. AB - The pathologic features, the terminology, the etiolgoy, and the causal relations of benign tumours of the liver associated with the use of oral contraceptives were reviewed during a study on six new cases. According to the literature the following points are emphasized: these tumours can be divided into two distinctive conditions, they are commonly called focal nodular hyperplasia and liver cell adenoma, whereas the name hamartoma seems rarely appropriated, they occur without any use of oral contraceptive, but this practice is probably responsible for their increasing number. PMID- 6256886 TI - [Thrombocytosis and anaemia (author's transl)]. AB - The authors found a significant statistical association between thrombocytosis and anaemia in 600 patients admitted to Hotel-Dieu of Marseille: p < 10(-3) with Chi 2 test and p < 5.10(-4) with Mann-Whitney test. There is also a significant correlation (linear and non-parametric Spearmann): r = -0,212; p < 10(-3); and a partial correlation between platelets count and weight of haemoglobin, which is independant of sedimentation rate. PMID- 6256887 TI - [Diabetic proteinuria. Statistical study (author's transl)]. AB - One hundred and six records belonging to diabetics carrying proteinuria were studied by uni-dimensional analysis, then multi-dimensional of thiry-six variables characterizing diabetes, its micro and macroangiopathic complications and the associated biological perturbations with regards to proteinuria. The results permit us to lessen the criterium of risks of the appearance of a diabetic nephropathy and also the linked anomalies. PMID- 6256888 TI - [Chronic lymphocytic leukemia, acute anergic tuberculosis, multiple caseous adenitis (author's transl)]. AB - The authors report an exceptional case of hematopoietic tuberculosis complicating a chronic lymphocytic leukemia, developing at first an acute tuberculous septicemia then a caseous disease of lymph glands. The usual difficulties of the diagnosis were increased by the underlying blood disease and it was done mainly thanks to an osteo-medullary biopsy and to the results of the specific proof treatment. PMID- 6256889 TI - [False-membrane pharyngitis and velopalatine paralysis: false diphteria, true infectious mononucleosis (author's transl)]. AB - Paralysis of the soft-palate occurring at the end of, or in conjunction with false-membrane pharyngitis with lymphadenopathies should prompt to think of diphteria. The reported case is concerning an 18 year-old girl in whom the affection of the last cranial nerves (IX-XI and XII) is falling within the rare but deceptive neurological forms of infectious mononucleosis. The evolution was favorable, as is normally the case when there are no respiratory complications. PMID- 6256891 TI - [Severe dwarfism with high plasma hGH levels and no somatomedin acitvity: Laron's syndrome (author's transl)]. AB - A case of Laron type dwarfism which is reported describes a clinical picture of isolated previous deficiency in growth hormone. But serum level of this hormone is found to be high both in regard to basic value and after ornithin stimulation. The somatomedin activity of the child serum was studied by two methods: biological assay and binding assay. This activity was found to be non-existent both in regard to basic conditions and after injection of hGH corroborating the diagnosis of dwarfism of Laron type. PMID- 6256890 TI - [Septicemia due to polyresistant Staphylococcus aureus (author's transl)]. AB - The efficiency of vancomycin hydrochloride in the treatment of septicemia due to polyresistant aureus staphylococcus is illustrated by the observation of a patient affected with a necrotic and hemorrhagic acute pancreatitis and post operative septicemic syndrome, which has been cured after a one-month treatment with a daily dose of two grammes. The vancomycin hydrochloride, because of its potential toxicity on the kidneys and cochlea should be reserved to the treatment of major staphylococcic infections. It could be prescribed either alone or in association, with a mean daily dose of 30 milligrammes a kilo, slowly administered by intravenous way. The side effects are prevented by adjusting the doses in case of renal insufficiency and by controlling the serous concentrations in case of a long continued treatment. PMID- 6256892 TI - [Polyneuritis after use of perhexiline maleate: quantimetric and ultrastructural study (author's transl)]. AB - The authors record a new case of polynevritis through a prolonged use of perhexiline maleate. The acute neurological episode occurred 14 months after the beginning of the treatment when the daily doses had been raised to 600 mg for 2 months. The biopsy of the peripheral nerve was carried out only 27 months later as the posology was brought down to 200 mg and the clinical symptomatology had almost completely diminished. This probably accounts for the unusual aspects observed on semi-thin and ultrathin sections: a very remarkable reduction of the number of myelinated fibers and the severity of the phenomena of Wallerian degeneration, contrasting with the rarity of intra-cytoplasmic multilamellar schwannian inclusions, classically observed in the course of polynevritis caused by perhexiline maleate. The direct toxic action of the drug upon the neuron has been discussed. PMID- 6256893 TI - [Calcinosis universalis associated with dermatomyositis. A report on five cases (author's transl)]. AB - Five patients with dermatomyositis developed calcinosis universalis, the calcinosis lesions being diffuse in three cases and localized to a subcutaneous site in the other two. The diffuse lesions developed in young subjects with severe dermatomyositis, and increased progressively during recovery from the muscle disease. Treatment was ineffective. Subcutaneous calcifications can be detected at an early stage by technetium pyrophosphate scintigraphy, while the fluid nature of the swellings due to a local inflammatory reaction is proved by ultrasonography. Good results are obtained after excision of those calcified masses requiring removal because of their size, site, or superinfection. PMID- 6256894 TI - [Cardiac localizations of lymphomas. A case report and review of the literature (author's transl)]. AB - A case of malignant lymphoma with cardiovascular manifestations is reported. It is a febrile form with compression of the aortic ring provoking a murmur simulating aortic valve disease with an Osler's graft. An analysis of the various complications due to lymphomas reported in the published literature emphasizes the iatrogenic nature of some of them: cardiac toxicity of chemotherapy, post radiotherapy pericarditis, and increased incidence of coronaritis after both cobalt and radiotherapy. The diagnosis of lymphomas in the cardiac area is difficult but should be evoked in case of febrile and chronic cardiopathy, no other etiology being detectable. PMID- 6256895 TI - [Leiomyosarcoma of the inferior vena cava (author's transl)]. AB - A further case of leiomyosarcoma of the inferior vena cava is described, bringing the total number reported in the published literature to 63. The tumor was located in the inter-renal segment of the vena cava, and was effectively removed by excision combined with venous reconstruction, enabling conservation of the renal veins. These malignant tumors occur more frequently in women, and their symptomatology varies according to their location in either the upper, middle or lower area of the inferior vena cava. Upper segment tumors are revealed by a Budd Chiari syndrome or obstruction of the right atrium and are usually rapidly fatal. Middle and lower segment tumors can be treated surgically, if diagnosis is made early enough and cavography is conducted. PMID- 6256896 TI - [An unusual cause of recurrent pericarditis: esophageal leiomyosarcoma (author's transl)]. AB - A supposed primary and cortico-sensitive pleuropericarditis in a 33-year-old woman with an apparent recovery of 9 months, revealed an esophageal leiomyosarcoma with a fatal issue following tumoral and purulent invasion of the mediastinum with an esophagobronchial fistula. Pericardis of tumoral origin may appear as a benign cryptogenetic affection sensitive to corticotherapy. Acquired esophagotracheobronchial fistulae are usually of neoplastic origin and the prognosis is extremely severe, survival being rarely more than three months. 69 cases of esophageal leiomyosarcoma have been reported in the published literature, but survival was prolonged in some patients treated surgically. Investigations for possible esophageal lesions should be conducted in all cases of pericarditis of unknown origin. PMID- 6256897 TI - [Clinical and diagnostic features in seven cases of sacro-iliac tuberculosis. Contribution of bone scintigraphy (author's transl)]. AB - Sacro-iliac tuberculosis was detected in seven African immigrants following attacks of sacrolumbar pain with fever, over a period of five years. Two of the patients had a previous history of tuberculosis, and in six out of the seven cases the osteo-articular affection was part of a multifocal tuberculous disease. The value of bone scintigraphy is discussed. Surgical treatment was performed together with medical therapy in three cases. PMID- 6256898 TI - [Chronic hepatopathy and progressive systemic sclerosis. Frequency of association with Gougerot-Sjogren's disease. A report on six new cases (author's transl)]. AB - Six patients with scleroderma (Barnett's type I and II) associated with hepatopathy are reported. Primary biliary cirrhosis was confirmed in four cases and was probably present in one case, while cirrhosis of unknown origin was present in the sixth patient. The outcome was fatal in two cases. Salivary secretions were reduced in all six cases, and a diagnosis of Gougerot-Sjogren's disease was confirmed in four patients. The frequency with which this triple association has been reported suggests that its incidence has been underestimated. PMID- 6256899 TI - [Cardiac manifestations of scleroderma. Prospective study of thirty cases (author's transl)]. AB - A prospective study was conducted to evaluate cardiac effects of scleroderma by means of phonomyography (30 patients) and ultrasound cardiography (18 patients). Clinically silent effusions can be detected by ultrasound cardiography, and 50 p. cent of the patients were found to have pericarditis through this investigative technique. Valvular lesions (mitral prolapsus) were present in a more important number than simply a coincidence. Measurement of myocardial relaxation appears to give the best indication of the specific myocardial lesion in this disease, and even may be of some prognostic value. PMID- 6256900 TI - [Cerebrovascular accidents in patients with migraine (author's transl)]. AB - Cerebrovascular accidents were observed in patients with migraine, and systematic investigation for the presence of a mitral valve prolapse was positive in all cases. Precise diagnosis requires ultrasonography examination. The pathogenicity of the cerebrovascular accidents in these patients could involve an emboligenic mechanism related to the prolapse of the mitral valve. PMID- 6256901 TI - [Hypoglycemia-inducing islet cell tumors. Measurement of blood glucose and insulin levels during operation. Results in seven cases (author's transl)]. AB - The identification of hypoglycemic langerhans tumours by the surgeon, being sometimes difficult, per-operative quantity determinations of the glycemia and insulinemia levels help to ensure that all the insulino-secretory tissue has been removed. The technical protocol described includes an excess of glucids. In the 5 cases of adenomas, between 30 and 60 minutes after exeresis, a distinct increase in glycemia was noted (on average 1,25 g/l) in comparison to the initial level; this increase was not however significant in the 2 observations of adenomatous hyperplasia. Following the removal of the lesion, the fall in insulinemia is also more noticeable in adenomas (reaching 75,8 per cent of the initial level) than in adenomatous hyperplasia. Nonetheless, the fall in the latter is still considerable (42,4 per cent). This examination would be the best test, excvept that the results are known only after the operation. The 7 patients operated on recovered after 2 enucleo-excisions, and 5 isthmo-corporal-caudal splenopancreatectomies, the average post-operative period reaching 4 years. PMID- 6256902 TI - [Study of adult morbidity and mortality from pneumococcus in hospital (author's transl)]. AB - The authors report the retrospective study of 333 cases of pneumococcal infection recorded in in-patients at the Rouen CHU (University Hospital Centre) from january 1974 to december 1978. Pneumococcal infection involves mainly the lungs (210 cases) according to different features. Pleural involvement is found in 70 cases only. Extra-respiratory localizations are less frequently encountered; they are represented mainly by meningitis (43 cases). Prognosis depends more on diathesis factors such as age and associated pathology than on the site of infection (cases with isolated respiratory involvement being usually less severe). The authors insist on the necessity of prevention especially by vaccination, of which indication is discussed. PMID- 6256903 TI - [Persistant pubertal gynecomastia. Biological study (author's transl)]. AB - 17 cases of peristant pubertal gynecomastia (which differs from physiologic breast enlargement by their volume and duration) were studied. Plasma estrogens and urinary phenol steroids excretion were found higher than in normal boys. The main biological finding in these subjects was a decrease of the plasma testosterone/estradiol ratio, and a moderate but transient increase in plasma prolactin. LH and FSH were within the normal range. In the mammary tissue, no estrogen receptor was detectable and aromatase activity was in the same range as in adipose tissue. Pathological examination showed a simulataneous proliferation of galactophoric and fibroblastic stroma. Thus, persistant pubertal gynecomastia could be related to an elevated sensitivity of the mammary tissue to a moderate increase of plasma estrogens. Such a sensitivity could be due to an insufficient masculinization of the mammary anlage during the intra-uterine life. PMID- 6256904 TI - [Migraine and tiapride. A controlled study (author's transl)]. AB - Patients complaining of migraine often consult the hepato-gastro-enterologist because of dyspepsia or "crise de foie". The treatment of the migraine must improve those symptoms which lead to a wrong diagnosis and to inadequate treatments. Several medication are available to treat the migraine. The tiapride, already known as being effective in common or secondary headaches, was given to 40 patients complaining of migraine. The controlled study done versus placebo clearly proves that this medication is effective. It should be used in the treatment of migraine. PMID- 6256905 TI - [Pathological patterns of reperfused myocardial infarction. Experimental study (author's transl)]. AB - The effect of the reperfusion on the pathological appearance of experimental myocardial infarction has been studied in the rat (87 animals). Following permanent ischemia (33 animals sacrified after 1, 6, 24 and 48 hours), there appeared a reproducible extended transversal infarction marked by an uniform sequence of histologic, histoenzymatic and ultrastructural changes. Following temporary ischemia (54 animals), the pathological patterns were marked by myofibrillar degeneration (contraction band necrosis), cellular edema, calcium deposits and interstitial hemorrhages. These changes appeared after reperfusion of short duration (10 minutes). Sarcolemmal and capillary permeability alterations could be the main factor involved in the reperfusion injury. Similar tissue damage have been found in clinical conditions in subendocardial hemorrhagic necrosis after cardiopulmonary by-pass, and in reperfused infarction. PMID- 6256906 TI - [Angiodysplasia or vascular malformations of the cervical spine (author's transl)]. AB - Following exploration by angiography , 45 patients with cervical spine malformations ( out of 220 cervicocephalic examinations for vascular malformations), were treated by embolization. The 45 cases included 13 facial lesions, 4 pharyngolaryngeal lesions, 2 cervical venous ectasias, 4 arteriovenous fistulae of the vertebral artery, 19 medullary lesions, and 3 pseudomalformations (hemangiopericytomas). Though embolization is difficult it is of value in definitely vascular occlusions (follow-up for 3 years), and miniaturization of catheters and balloon sounds enables very selective occlusion of vascular tumors or malformations to be carried out, micro-emboli of 30 to 500 mu have been obtained. PMID- 6256907 TI - [Focal nodular hyperplasia of the liver. A report of seven cases (author's transl)]. AB - Seven cases of focal nodular hyperplasia of the liver are reported. The clinical and biological data are poor ; the authors define the morphological aspects : cirrhosis, bile ducts agenesis, vascular malformation and emphasize these changes as a liver dysgenesis. PMID- 6256908 TI - [Recurrent infections in hematologic diseases treated with cefoxitine (author's transl)]. AB - Forty febrile patients during several hematologic diseases (28 acute leukemias, 8 lymphocytic chronic leukemias, 3 drug induced agranulocytosis, 1 myeloid aplasia) received intensive combination antibiotherapy including cefoxitin (with gentamicin in all cases : Carbenicillin was added in 17 cases). Thirty-five patients had severe neutropenia before treatment. Infection's regression was obtained in 35 cases (in spite of persistence of neutropenia in 20 cases). No local, general or biological toxicity was observed. PMID- 6256909 TI - [Late diagnosis hyperandrogenism due to adrenal enzyme deficiency (author's transl)]. AB - Six women aged from 17 to 30 years (mean: 21 years) were referred on account disorders which had begun at puberty and had been present for 3 to 15 years. The reasons for consulting were hirsutism in 5 cases and sterility in one. The patients' height (1.61 to 1.70 m; mean: 1.64 m) and weight (54 to 70 kg; mean: 59 kg) were normal. Three women menstruated regularly and 3 had anovular spaniomenorrhaea. Hirsutism with enlargement of the clitoris (Prader's stage I) was apparent in all six cases. Three patients had permanent, though moderate hypertension. The biochemical changes essential to the diagnosis were as follows: 1) in 2 women with 21-hydroxalyse deficiency there was a rise in cortisol precursors (plasma 17-OH progesterone and its urinary metabolite, pregnanetriol). In 4 women with 11-hydroxylase deficiency urinary 17-OH corticosteroids were increased; two had high desoxycorticol levels. A rise in plasma desoxycortisol/cortisol ration under tetracosactrin stimulation is of considerable diagnostic value; 2) plasma androgens (testosterone, delta 4 androstenedione) and their urinary metabolites (17-ketosteroids) were increased; 3) all abnormalities disappeared when the adrenal function was suppressed. Under dexamethasone treatment hirsutism became stabilized or even regressed, blood pressure values rapidly returned to normal, menstrual disorders disappeared and ovular cycles were established. Three women became pregnant and delivered on term. PMID- 6256910 TI - [Pseudo-tumoral human African trypanosomiasis due to Trypanosoma gambiense. Clinical and tomodensitometry study (author's transl)]. AB - The authors report an observation of african trypanosomiasis due to Trypanosoma Gambiense, clinical signs included massive and progressive hemiplegia, papillary edema and vascular shift from median line at arteriography. These pseudo tumoral clinical features are unusual in this disease. Asymetrical heterogenous hypodensities of the centrum semioval are dominant in the initial CT scanner aspect. The confrontation of CT scanner images to the clinical and evolutive data suggests the presence of associated cerebral edema and demyelination. With treatment, hypodensities were regressing while images of subcortical atrophy appeared. Lastly, in spite of severe general signs and the importance of neurological deficit, arsenical treatment associated with high doses of corticotherapy lead to a rapid improvement. PMID- 6256911 TI - [Influence of the computed tomography in brain disorders. Retrospective study of 10,000 investigations (author's transl)]. AB - On the basis of 10,000 examinations conducted over a period of 4 years and 7 weeks (1974-1979), the authors quantify the influence of computed tomography on neuroradiological diagnostic procedures. Findings during operation, at autopsy, or from follow-up over a sufficiently long period, are used to compare the diagnoses established after computed tomography with those suggested by other investigational methods. The regular increases in pathological observations demonstrates the increasingly precise selection of patients orientated towards the scanner. Computed tomography significantly reduces the frequency of invasive neuroradiological explorations, with both medical and socio-economic consequences. Computed tomography is greatly superior to morphological scintigraphic investigations. PMID- 6256912 TI - [Immunological classification of acute lymphoblastic leukemias (author's transl)]. AB - Immunological markers in acute lymphoid leukemia complete the cytological study and allow a new classification. 44 cases of acute lymphoid leukemia were investigated for the presence of T and B membrane markers on bone marrow and/or peripheral blood lymphoblasts. 20 per cent of cases had T lymphoblasts: 10-90 per cent of the lymphoblastic cells exhibited T cells markers (E-Rosetting). 10 per cent of cases had B lymphoblasts: these cells have shown monoclonal surface immunoglobulin. 70 per cent of cases had "non T, non B" lymphoblasts: some of these lymphoblasts formed EAC-Rosettes. These techniques of lymphocytes studies are fruitful in furthering understanding of the structure function relationship of these cells. PMID- 6256913 TI - [Immunological classification of lymphoma and lymphocytic leukemias (author's transl)]. AB - Lymphocyte surface immunoglobulin, E-rosettes and EAC-rosettes were studied in 91 patients with chronic lymphocytic leukemia of well differentiated lymphosarcoma and 16 patients with poor differentiated lymphosarcoma (including lymphoblastic lymphoma and histiocytic lymphoma of Rappaport). The tests were performed on the malignant cells in peripheral blood or in lymph nodes. In well differentiated proliferation only one had T malignant cells. All the others had B malignant cells. In poor differentiated proliferation: 50 per cent of cases had "B" lymphosarcoma cells, 21 per cent of cases had "T" lymphosarcoma cells, 29 per cent of cases had "non T, non B" lymphosarcoma cells. These results show the heterogeneity of both functional aspects and stages of maturation in lymphoma cells. PMID- 6256915 TI - [The intestinal polyposes (author's transl)]. AB - In a general review of the different varieties of the intestinal polyposes, emphasis is laid upon the main three types of the so-called "genetic polyposes" (juvenile polyposis, Peutz-Jeghers syndrome, and adenomatous polyposis) because of their peculiar interest concerning the pathological diagnosis, prognosis and genetic background. A correct histological diagnosis is of the utmost importance before an appropriated treatment can be initiated. PMID- 6256916 TI - [Association of hyperlipidemia, acute pancreatitis and diabetic keto-acidosis. A case report (author's transl)]. AB - A 32-year-old man was admitted semi-comatose with digestive troubles to the hospital. A diabetic keto-acidosis was discovered. The diabetes was known by the patient for one year and a half, but it was not treated. Furthermore the laboratory studies showed a hyperlipidemia (type V) and an increase in pancreatic enzymes. The hyperlipidemia disappeared with insulin therapy. The chronology of the facts was probably: a hyperlipidemia associated with the diabetes, responsible of an acute pancreatitis, which induced a keto-acidosis. PMID- 6256914 TI - [Diagnostic aspects of cerebral arterial occlusion in infants and children (author's transl)]. AB - The authors have studied the bases of the clinical and CT diagnosis of cerebral arterial occlusion in children from a series of 16 cases. The sequential evolution of the CT appearance seems characteristic depending on the time elapsed since the onset. Contrast enhancement, concerns mainly the grey matter, is maximum during the second and third weeks and should be looked for during this period. The aetiology remains usually hypothetic. Some data, including the angiographic aspect of "endarteritis" may suggest an infectious pathogeny. PMID- 6256917 TI - [A case report of septicaemia due to Campylobacter fetus variety intestinalis on a cancerous patient (author's transl)]. AB - The authors report a case of Campylobacter fetus septicaemia from a cancerous patient. The bacterium was isolated from three blood cultures. The infection characteristics are briefly discussed. PMID- 6256918 TI - [Cutaneous manifestations of mediterranean periodic disease. Concerning an observation. Review of the literature (author's transl)]. AB - Mediterranean Periodic Disease is frequently encountered in non-aschenazic Jews and in Armenians. Aside from the classic triad of pseudo-palustral febrile crises, paroxysms of abdominal and articular pain, and a biological syndrome of inflammation; cutaneous manifestations were noted in 25 to 35% of the cases according to various authors. The most commonly encountered lesions consisted of erysipel-like plaques and subcutaneous nodules. We observed the case of a 47 years old Armenian male, afflicted with Mediterranean Periodic Disease for 30 years in which the dermatologic symptoms are quite classic aside from a vitiligo having progressively appeared since 15 years. Possibly a coincidental association, but to the best of our knowledge, which has not as yet been reported. PMID- 6256919 TI - [Continuous recording of plasma glucose level after glucose tolerance and 3 different breakfast. Search for a normal post-prandial plasma glucose (author's transl)]. AB - We have studied glucose tolerance test (GTT) and glucose after 3 different breakfast (50, 100, 150 g CHO), in order to define a postprandial glucose level for the detection and control of diabetes mellitus. If the breakfast is sufficient enough (100 or 150 g CHO) the response after breakfast is similar to GTT. The post meal glucose is < 1,5 g/L mean + 2 SD) at 35 mn and < 0,97 g/L at 108 mn. Glucose level over these limits set to search a diabetes. Nevertheless this study is restricted by two points: the subjects are young and the load must be sufficient enough (over 100 g CHO). PMID- 6256920 TI - [Flaubert, the unsatisfied]. PMID- 6256921 TI - Familial chronic mucocutaneous candidiasis successfully treated with oral ketoconazole. AB - A father and son, both suffering from chronic mucocutaneous candidiasis, were successfully treated with oral ketoconazole, a water-soluble imidazole compound. No toxic side-effects occurred during treatment. Treatment was given for about 8 months with diminishing does of ketoconazole. The disease cleared completely about half-way through the course of treatment and did not relapse within 1 month of discontinuing the drug. The only immunological abnormality was a depression in vitro of neutrophil chemotaxis. This became normal during therapy and was regarded as being a result of the disease and not as its cause. PMID- 6256922 TI - Effects of neutral proteases from human leukocytes on structure and biological properties of human factor VIII. AB - Human factor VIII was purified from cryoprecipitate and incubated for up to 24 hours with four neutral proteases of human blood leukocytes, namely, with elastase-like protease (ELP), chymotrypsin-like protease (CLP), collagenase and gelatinase. Electrophoretic patterns showed a reproducible sequence of degradation of factor VIII and of its 230,000 molecular weight subunit by ELP and CLP. Intermediate products were similar but those resulting from exhaustive proteolysis by ELP and CLP differed distinctly from each other. Procoagulant activity of factor VIII was rapidly and completely destroyed by ELP and CLP before visible electrophoretic changes would be detected. No increase in this activity was observed prior to its destruction. Von Willebrand factor (ristocetin cofactor) activity was considerably more resistant to ELP and CLP and declined in rough relation to degradation of highly aggregated forms of factor VIII. ELP and CLP produced a pronounced progressive increase in the Laurell reaction antigen. Normal human plasma showed a high potency to inhibit ELP and CLP. Large doses of these enzymes (300 microgram per ml) produced in the plasma medium only a moderate fall in factor VIII procoagulant activity. Collagenase and gelatinase did neither degrade factor VIII nor change its biological properties. PMID- 6256923 TI - [Klippel-Trenaunay-Weber syndrome]. PMID- 6256924 TI - Liver scanning in short interval autopsy material of cancer patients. AB - The accuracy of liver scanning, alkaline phosphatase and 5'-nucleotidase in the detection of the hepatic metastases was studied in short interval autopsy material of 243 cancer patients. The highest percentage of correct diagnosis was by 5'-nucleotidase, alkaline phosphatase was the second, and scanning third. The overall accuracy of liver scan was 68 per cent. It was the better the shorter the time interval between scanning and autopsy. The higher percentage of incorrect diagnoses of the scan was related to a larger number of false positives, the causes of which were to be verified only in half of the cases. PMID- 6256925 TI - Steroid secretion by ACTH-stimulated human fetal adrenal tissue during the first week in organ culture. AB - Fetal adrenal tissue has been reported to lose its in vivo secretory pattern by virtue of a loss of fetal zone cells after the first week in culture. Consequently, we studied the steroidogenic capacity and the responsiveness to ACTH of human fetal adrenal tissue during the first week in organ culture. The culture medium was removed daily and assayed for cortisol and dehydroisoandrosterone sulfate (DS). First, as the concentration of ACTH in the medium was increased from 0 to 1 micrograms/ml steroid secretion increased. When tissue fragments were maintained in the absence of ACTH for 3 to 4 days, there was a striking increase in steroid secretion upon addition of ACTH to the medium, with larger rates of secretion of cortisol than DS being observed. Second, the steroidogenic capacity of the separate zones of the fetal adrenal gland was assessed. Tissue from the fetal zone secreted large amounts of DS and small amounts of cortisol, whereas neocortex tissue secreted similar quantities of DS and cortisol. Third, fetal zone tissue was maintained the absence of ACTH for 4 days and thereafter ACTH was added to the media for an additional 6 days. In this experiment, there was a marked increase in DS secretion rate after the addition of ACTH and a smaller increase in cortisol secretion. PMID- 6256927 TI - Irreversible attachment of immunoglobulins and F(ab')2 fragments to their specific cell membrane antigens. AB - Antiserum was raised in sheep against rat kidney glomerular basement membrane, and the antibodies and their F(ab')2 fragments were prepared. These were reacted with one arm of the bifunctional reagent toluene diisocyanate at pH 7.5 and injected into the tail vein of rats. Kidney sections were taken from the rats and, after washing, incubated at pH 8.5 to permit the other arm of the toluene diisocyanate to become reactive. This procedure resulted in the specific irreversible attachment of the antibodies and their F(ab')2 fragments to their corresponding glomerular basement membrane antigens. PMID- 6256926 TI - Direct inhibition of testosterone synthesis in rat testis interstitial cells by ethanol: possible sites of action. AB - The present in vitro studies using interstitial cells of adult rat testes demonstrated that ethanol inhibits LH- and 8-bromo-cyclic AMP-stimulated testosterone synthesis, pregnenolone- and progesterone-stimulated testosterone synthesis, and basal testosterone synthesis. However, the patterns of inhibition following exposure to 0.22 to 880 or 1100 mM ethanol were different. In general, the inhibition curves for LH-, 8-bromo-cyclic AMP-, pregnenolone- and progesterone-stimulated testosterone synthesis were biphasic, with a gradual slope from 0.22 to 220 mM ethanol, and a sharper slope with concentrations of ethanol greater than 220 mM. Basal testosterone synthesis was reduced only to 74% of control with ethanol concentrations up to 44 mM, and higher concentrations of ethanol reduced testosterone synthesis no further. The effect of ethanol on Lh stimulated cyclic AMP accumulation showed an even different pattern: some of the lower concentrations of ethanol inhibited cyclic AMP accumulation, while higher levels of ethanol progressively increased cyclic AMP accumulation. These studies demonstrate that isolated interstitial cells are highly sensitive to the direct effects of ethanol; they also suggest that the principle site of ethanol inhibition may be at the level of the smooth endoplasmic reticulum where progesterone is converted to testosterone. PMID- 6256928 TI - Genetics in urogenital cancer. PMID- 6256930 TI - Experimental and field evaluation of a new oral vaccine for TGE. PMID- 6256929 TI - [Tonsillitis in mixed respiratory viral infections]. PMID- 6256931 TI - Heavy and trace metal determinations in cattle grazing pastures fertilized with treated raffinate. PMID- 6256932 TI - Electron-microscopic study of the villous adenoma of the colon. AB - The author studied the electron-microscopic peculiarities of villous adenoma as illustrated by 12 cases. She found that the dominant cells of villous adenoma are undifferentiated epithelial cells. Electron-microscopic signs of malignant transformation were revealed by nuclear changes, by the changes in the cytoplasmic membrane and by the immaturity of cells. Leuchtenberger's inclusion bodies are assumed to develop by herniation of cytoplasmic processes of immature tumour cells. In one tumour associated with electrolyte loss, atypical cells were observed with an electronmicroscopic picture indicative of an intense secretory activity. However, the secretion drops differed from the normal mucus drops of the mature goblet cells of the colonic mucosa. The author believes it to be possible that the tumour cells of atypical morphological appearance secrete mucus of abnormal composition which could be responsible for the syndrome of electrolyte loss. PMID- 6256933 TI - Multilocular renal cyst. Case report, ultrastructure and review of the literature. AB - Multilocular renal cyst is an uncommon focal, unilateral, cystic, epithelial lesion of uncertain pathogenesis. Because nephroblastomatous foci have been found on microscopic examination of several of the reported cases, some authors have proposed that multilocular cysts are differentiated and cystic forms of Wilms' tumour. This proposition is analysed and it is concluded that three possibly interrelated lesions may be defined: (1) Wilms' tumours showing cystic differentiation. (2) Lesions macroscopically indistinguishable from multilocular cyst containing variably differentiated nephroblastomatous foci. All such cases have been described in infants. (3) Typical multilocular renal cysts, which have described in children and adults. Review of the literature shows that several cases have been included in the second category solely because of the presence of small intraseptal tubules. Consequent anomalies of interpretation are highlighted and a further case of multilocular cyst in an adult female is reported in which ultrastructural examination, recorded for the first time, confirms the epithelial nature of the cyst lining cells which resemble simplified renal tubular epithelium. PMID- 6256934 TI - Myofibroblasts in soft tissue sarcomas. AB - A series of 129 soft tissue sarcomas was examined ultrastructurally to determine in which neoplasms and to what extent myofibroblasts could be demonstrated. Twenty cases of fibromatosis and fasciitis served as controls. Myofibroblasts were identified in all 30 cases of malignant fibrous histiocytoma and all 4 cases of well-differentiated sclerosing liposarcoma. Though most numerous in areas of desmoplasia, in no instance did myofibroblasts constitute the dominant cellular constituent of either neoplasm. Myofibroblasts were identified with lesser frequency and in smaller numbers in fibrosarcoma, synovial sarcoma, malignant hemangiopericytoma and neuroblastoma. None were observed in a wide assortment of diverse sarcomas in which desmoplasia was not a feature. In comparison each lesion judged by light microscopy to represent either fibromatosis or fasciitis was composed principally of myofibroblasts. The demonstration of abundant myofibroblasts within a soft tissue lesion which has been subjected to wide sampling strongly suggests a benign proliferative process as opposed to a malignant neoplasm. It is hypothesized that myofibroblasts observed within collagenized regions of soft tissue sarcomas may constitute an expression of host response to neoplasia. PMID- 6256935 TI - Ataxia-telangiectasia with renal cell carcinoma and hepatoma. AB - This paper reports the occurrence of renal cell carcinoma, hepatoma and malignant hepatic mixed tumor in a 22-year-old male with ataxia-telangiectasia (AT). Incidence of various malignant neoplasms is high in the patients with AT. The majority of these are lymphoreticular tumors and leukemia, and epithelial tumors are rare. This report is the first case with renal cell carcinoma and the second with hepatoma. The reason for a low incidence of epithelial tumors in AT is still obscure. It is possible that as the result of abnormal aging the tumors expected in the aged will occur in longer survivors with AT. PMID- 6256936 TI - Noncoordinate expression of murine mammary tumor virus gene products. PMID- 6256937 TI - A cycloheximide-enhanced protein in cytomegalovirus-infected cells. PMID- 6256938 TI - Persistent infections of green monkey kidney cells initiated with temperature sensitive mutants of simian virus 40. PMID- 6256939 TI - Intracellular SV40 nucleoprotein complexes: synthesis to encapsidation. PMID- 6256940 TI - Viral and cellular factors that influence cell fusion induced by herpes simplex virus. PMID- 6256941 TI - Induction of DNA polymerase activity after superinfection of Raji cells with Epstein-Barr virus. PMID- 6256943 TI - Recombination of influenza A strains with fowl plague virus can change pneumotropism for mice to a generalized infection with involvement of the central nervous system. PMID- 6256944 TI - Biology of simian virus 40 (SV40) transplantation antigen (TrAg). VII. Induction of SV40 TrAg in nonpermissive mouse cells by early viable SV40 deletion (o.54/0.59) mutants. PMID- 6256942 TI - Sequential passage of influenza virus in embryonated eggs or tissue culture: emergence of mutants. PMID- 6256945 TI - Generation of defective interfering particles of vesicular stomatitis virus in Aedes albopictus cells. PMID- 6256946 TI - The production of high yields of infectious vesicular stomatitis virus in A. albopictus cells and comparisons with replication in BHK-21 cells. PMID- 6256947 TI - Equine infectious anemia virus, a putative lentivirus, contains polypeptides analogous to prototype-C oncornaviruses. PMID- 6256948 TI - Phosphorylation of SV40 large T antigen in SV40 nucleoprotein complexes. PMID- 6256950 TI - Influenza virus RNA segment 7 has the coding capacity for two polypeptides. PMID- 6256949 TI - Glycoprotein micelles isolated from vesicular stomatitis virus spontaneously partition into sonicated phosphatidylcholine vesicles. PMID- 6256951 TI - Influence of influenza and Sendai virus on the rotational mobility of Band 3 proteins in human erythrocyte membranes. PMID- 6256952 TI - Effect of n-butyrate on cellular and viral DNA synthesis in cells latently infected with Epstein-Barr virus. PMID- 6256953 TI - Identification of poliovirus precursor proteins by immunoprecipitation. PMID- 6256954 TI - [Oxidative phosphorylation of Krebs cycle substrates in experimental treatment of enterocolitis with cytochrome c]. AB - After administration of exogenous cytochrome c into rats with enterocolitis, caused by salmonellae, tissue respiration and oxidative phosphorylation in presence of succinic, alpha-ketoglutaric, pyruvic and oxaloacetic acids were increased in the liver tissue. Treatment with cytochrome c produced a positive effect on the general state of an organism, led to disappearance of macroscopic alterations in mucosa of small intestine. The data obtained suggest that cytochrome c possesses the positive therapeutic effects in enterocolitis caused by salmonellae. PMID- 6256956 TI - [Effect of adrenaline on the ATPase activity of rat liver plasma membranes]. AB - In vivo and in vitro adrenaline affected dissimilarly the activity of Na+, K+-, HCO3- and Mg2+-ATPases from plasmatic membranes of rat liver tissue. Inhibition of Na+, K+-ATPase and stimulation of Mg2+-ATPase activities were observed within 1, 24 and 48 hrs after subcutaneous administration of the hormone at a dose of 0.3 and 1.0 1.0 mg/kg of body weight; at the same time, HCO3- -ATPase activity was inhibited by adrenaline at a dose of 1.0 mg/kg and stimulated--at a dose of 0.3 mg/kg. After in vitro incubation of the plasmatic membranes with 5.45 10(-6)- 10(-4) M of the hormone the activities of HCO3- - and Na+, K+-ATPases were inhibited but Mg2+-ATPase activity was not altered. The data obtained suggest that the ATPases, responsible for the active membrane transport of K+, Na+ and HCO3-, are highly sensitive to adrenaline. PMID- 6256955 TI - [Changes in phospholipid metabolism in subcellular structures of cardiac muscle of rabbits with experimental myocardial infarction]. AB - Alteration in phospholipid turnover was studied in subcellular structures (nuclei, mitochondria, microsomes) of rabbit heart muscle within various postinfarctional periods (7, 14 and 21 days). The specificity of alterations in phospholipids as well as dissimilar direction of the alterations were observed in different subcellular structures of heart cells under conditions of myocardial infarction. Administration of etpenale contributed to increased synthesis of phospholipids (especially in mitochondrial fraction) with subsequent trend to normalization. PMID- 6256957 TI - [Structure and biosynthetic functions of rat liver mitochondrial fractions]. AB - Two mitochondrial fractions, dissimilar in their sedimentation characteristics, were isolated from rat liver homogenates using differential centrifugation. Morphological peculiarities of mitochondria of both these fractions, their capacity to protein and DNA synthesis as well as activities of several key enzymes of DNA biosynthesis were studied. The differences observed are discussed in terms of age dissimilarities of the mitochondria in the population. PMID- 6256958 TI - [Concentration of free and esterified cholecalciferol in the tissues of rats with hypervitaminosis D]. AB - Within 4 hrs after intravenous administration into rats of cholecalciferol maximal concentration of the compound, which was increased depending on the dose used, was found in liver tissue, within 24 hrs--in kidney. Increase in cholecalciferol doses led to an increase in the ratio of the esterified compound to its free form. Content of the esterified cholecalciferol reached the highest level in kidney within 4 hrs and 24 hrs after administration of all the doses of cholecalciferol studied. PMID- 6256959 TI - [Reconstitution of cytochrome oxidase with liver and hepatoma 27 mitochondrial lipids]. AB - Activity of cytochrome oxidase, incorporated into the lipoprotein vesicles /proteoliposomes/ in the course of self assembly procedure, was studied. For this purpose the lipids were used, which were isolated from mitochondria of rat liver tissue and of hepatoma 27. The enzymatic activity was distinctly increased after the reconstriction using liver mitochondrial phospholipids; the hepatoma lipids were not effective. An agent uncoupling the oxidative phosphorylation activated the oxygen utilization by cytochrome oxidase in proteoliposomes containing phospholipids of liver mitochondria, but not of hepatoma organelles. A difference in electrical potentials, generated by cytochrome oxidase reaction on proteoliposome membranes containing the phospholipids from liver mitochondria, was distinctly higher as compared with proteoliposomes containing the lipids from mitochondria of tumors. PMID- 6256960 TI - [Liposomes and cAMP in lysosome membrane stabilization]. PMID- 6256962 TI - [Isolation and radiometric determination of rat liver ATP: thiamine diphosphate phosphotransferase activity]. AB - A radioassay was developed for estimation of the thiamin diphosphate kinase activity (EC 2.7.4.15); 14C-TDP was used as a substrate. After termination of the reaction (formation of TTP), the products obtained were separated using ion exchange chromatography on SP-Sephadex C-25. The method developed was very sensitive and enabled to estimate the enzymatic activity in tissue homogenates. TDP-kinase was isolated from rat liver with a 70-fold purification. Dependence of the reaction rate on pH value, concentrations of the enzyme and thiamin were studied. PMID- 6256961 TI - [Collagen metabolism indices, and plasma concentrations of lipids, cyclic 3',5' AMP, and certain hormones in 40-59-year-old men]. AB - Concentrations of protein-bound hydroxyprolin, free hydroxyproline, cholesterol, alpha-cholesterol, triglycerides, testosterone, estradiol, insuline and 3',5' cAMP were estimated in blood plasma of 40-59 years old men. The persons thus examined were divided into three groups depending on the content of protein-bound hydroxyproline. Only in blood plasma of persons with low concentration of the protein-bound hydroxyproline a direct correlation was found between cAMP and testosterone, cAMP and alpha-cholesterol, between cAMP and the ratio of the cholesterol from atherogenous lipoproteins to the cholesterol from alpha lipoproteins, as well as reciprocal correlation--between cAMP and insulin. The increase of protein-bound hydroxyproline concentration and the decrease of cAMP content in blood plasma might be related to proliferation of smooth muscle cells in the vessel wall, dependent, first, on alteration in the ratio of lipoproteins of various density in blood plasma and, second, on alteration in the hormone concentration in blood and tissues. PMID- 6256963 TI - [New means of isolating restriction endonuclease preparations using organic solvents]. AB - A new procedure is developed for isolation of highly purified preparations of restrictional endonoucleases Bam HI and Eco RI by means of fractionation with isopropyl alcohol. Restrictional endonuclease Bam HI, practically free of unspecific nucleases, was isolated after ultrasonic destruction of cells, precipitation of the restrictases with isopropanol and chromatography on DEAE cellulose. Additional chromatography on hydroxyapatite enabled to obtain the homogenous preparation of Bam HI restrictase, as shown by polyacrylamide gel disc electrophoresis. Other organic solvents (acetone, ethanol) might be also used for purification of the restrictional endonucleases. PMID- 6256964 TI - [Cyclic 3',5'-adenosine monophosphate in the liver of rats with experimental rheumatoid arthritis]. AB - Content of cAMP was distinctly decreased in rat liver tissue within the first days of development of experimental rheumatoid arthritis (adjuvant arthritis). Within 6 days the content of cAMP was slightly increased in liver tissue of the arthritic rats but it was lowered 2-fold as compared with controls. The content of cAMP was quite unaltered during subsequent course of the impairment (within 25 days). In blood plasma of patients with rheumatoid arthritis the content of cAMP was decreased more than 2-fold as compared with its concentration in blood of donors. Possible importance of cAMP deficiency in pathogenesis of rheumatoid arthritis is discussed. PMID- 6256966 TI - [Effect of whole-body vibration on glucose concentration and gluconeogenesis enzyme activity in the blood and tissues of rabbits with experimental hypercholesterolemia]. AB - Under conditions of experimental hypercholesterolemia vibration caused variable alterations in glucose-6-phosphatase activity and an increase in fructose-1,6 diphosphatase activity in rabbit tissues as well as an increase of glucose content in blood. At the same time, consumption of glucose and carbohydrate metabolism were altered in kidney cortex, heart and skeletal muscles under conditions of combined effect of total-body vibration and hypercholesterolemia. PMID- 6256965 TI - [Effect of cGMP administration on certain metabolic processes in rat wound tissues]. AB - Administration of cGMP immediately after an operation caused the early activations of collagen biosynthesis in skin, muscles and granulations. Within the 5 day content on collagen was increased two-fold in granulations of experimental animals as compared with controls. Stimulation of the label incorporation into some muscle proteins and intensification of glycogen metabolism were also observed after the cGMP treatment. Morphologic analysis of tissues and measurement of the wound area in dynamics of healing were carried out. The data obtained suggest that administration of cGMP into the operated animals activated metabolism in wound tissues and stimulated their healing. PMID- 6256967 TI - [Sensitivity of brain Na, K-ATPase to acetylcholine following heat treatment of membrane preparations]. AB - Microsomal preparations of Na, K-ATPase, isolated from dog and bovine brains, were completely insensitive to acetylcholine (10(-6)-10(-2) M) under standard experimental conditions. At the same time, heat pretreatment of membranes induced alterations of the enzymatic activity in presence of low concentrations (10(-6) 10(-5) M) of the neurotransmitter. Acetylcholine stimulated the Na, K-ATPase activity after storage of the preparations at 22 degrees within 30 or 60 min inhibited the activity at 37 degrees. Addition of the transmitter during the preincubation increased its effect. The maximal values of Na, K-ATPase activation and inhibition constituted 30% and 24%, respectively. D-tubocurarine (10(-6)-10( 5) M) and atropine (10(-4) M) did not eliminate and eserine (10(-4) M) did not alter the induced effect of acetylcholine. The effects of acetylcholine were changed to the opposite ones within 70-90 days of storage of the preparations. The phenomenon might be simulated by "ageing" of microsomes at 37 degrees within 3-6 hrs. PMID- 6256968 TI - [Age and seasonal characteristics of Na, K- and Mg-ATPase activities in different brain structures]. PMID- 6256969 TI - [Surgical treatment of adenocarcinoma of the stomach and cecum with Krukenberg's metastases (case report)]. PMID- 6256970 TI - [Effect of bacterial collagenases on the connective tissue around plastic implants during development of sarcoma]. PMID- 6256971 TI - [Adrenal cortex function in trophoblastic disease]. AB - In 100 patients with trophoblastic tumors the functional activity of the adrenal cortex was examined before and after chemotherapy. Androgen-producing function of the adrenal cortex was found to be reduced as well as the absolute number of excreted 17-ketosteroids separate fractions and their ratio. The glucocorticoid function of the adrenal cortex shows a monotonous character. Only in patients having uterine chorion-epithelioma with metastases a reliable reduction of the fraction of 11-hydroxy-17-ketosteroids is noted before and after chemotherapy, while the per cent content of free 17-oxy-corticoid fraction is increased with regard to their total amount. Successful chemotherapy, associated with a lower titre of chorionic gonadotropins up to its complete disappearance, does not result in normalization of values characterizing the functional activity of the adrenal cortex. PMID- 6256972 TI - [Changes in the cyclic AMP level in the cells of murine sarcoma induced by monkey adenovirus SA7(C8) during tumor growth enhanced by lymphocytes from intact syngeneic mice]. AB - Under consideration is the problem of changes in the cAMP level in sarcoma of mice CBA with routine and enhanced rate of growth. To this end the kinetics of sarcoma growth, induced by monkey adenovirus SA7 (C8), with common and stimulated by lymphocytes from intact syngeneic animals rates of growth was studied. Simultaneously, the kinetics of intracellular cAMP content in tumor cells was studied too. It was found that there is an inverse dependence between the cAMP content and the rate of sarcoma SA7 (C8) growth. Use of one type of tumor cells with the predetermined different rate of growth makes it possible to relate the changes in the content of intracellular tumor cell cAMP with changes being due to growth potentials. PMID- 6256973 TI - [Serotypes of herpes simplex virus and their association with cervical cancer]. AB - Comparative studies of some properties of Herpes simplex viruses type I and II and their ability to reproduce latent infection in vitro revealed no essential differences between them. Virus-neutralizing and hemagglutinating antibodies to the virus type II are detected reliably more frequently in cervical cancer patients than in healthy ones. Forty six per cent of cervical cancer patients and thirty nine per cent of healthy females along with antibodies against the virus of serotype II showed a specific cellular response, which was demonstrated in the reaction of leucocyte migration inhibition. In patients with dissemination of the disease there is an inhibited cell immunity to Herpes virus without changing of the humoral resistance. PMID- 6256974 TI - [Clinical trial of a variation of combined radiation therapy of recurrent rectal cancer in women]. AB - The results of clinical testing of the variant of associated radiotherapy for recurrent rectal cancer in 34 female patients are reported. Distant grid gamma therapy in the regime of uneven irradiation was associated with intracavitary irradiation and gammatherapy from open fields. An average focal dose under uneven irradiation was 86 Gy (8600 rad) in intracavitary gammatherapy--30 Gy (3000 rad), in open field irradiation--30 Gy (3000 rad), the radiation stress being 1.5-2 times increased within the limits of normal tisues tolerance compared with routine variants of irradiation. No marked radiation injuries hampering the continuation of the treatment were observed in the period to follow. Among 34 patients in 8 (23.5%) the complete tumor regression was gained. PMID- 6256975 TI - [Ultrastructure of the polysome-lamella complexes in ovarian cancers]. AB - Electron-microscopy was used to study the intraoperative material in 37 patients with serous (24), mucinous (8) and endometroid (5) ovarian neoplasms of benign, boundary and malignant forms. It was shown that the polysome-lamellae complexes are characteristic only of the carcinoma epithelium and practically are observed neither in benign nor in boundary analogs. This may serve an additional criterion of a malignant nature of neoplasms at the ultrastructural level. Taking into account the architectonics 3 variants of the polysome-lamellae complexes should be distinguished: polysome-lamellae, lamellae and lattice structures. All these variants may be encountered in one and the same tumor. PMID- 6256976 TI - [Rous virus-induced sarcoma study of Macaca mulatta monkeys]. AB - The Carr-Zilber strain of Rous sarcoma virus is highly oncogenic for adult monkeys of the species Macaca mulata. In the present study the authors examined some characteristics of tumor growth, when the tumor either regressed or progressed until it killed its host. The kinetics of antibody formation to antigens coded as CZ-RSV was followed in animals with a different course of tumor disease. The sera of animals under test contained virus-neutralizing antibodies in addition to gs antibodies. PMID- 6256977 TI - [Evaluation of presently used threads for suturing blood vessels]. PMID- 6256978 TI - [Chemotherapy of malignant brain tumours: principles, difficulties, results and strategies (author's transl)]. AB - Long-lasting therapeutic results have not yet been reached in brain tumour chemotherapy. Mean survival rates in patients with malignant gliomas (glioblastoma multiforme, astrocytoma III-IV) can only be increased for a few months, even with the administration of alkylating nitrosourea derivatives which are in common use these days. In addition to general difficulties of chemotherapy, the well-protected site of the target organ, the brain, is responsible for that fact. This organ has special barrier mechanisms which reduce environmental influences; furthermore the kinetics of brain tumour cells and the interaction of pharmacological agents and tumourous cells are only scarcely known. Finally there are difficulties in the comparison of different samples because criteria of sampling are not always identical and an unequivocal terminology is not used in brain tumour classification. Nevertheless there has been some therapeutic progress after the introduction of urea derivatives into brain tumour chemotherapy, be it as single agent, combination or adjuvant chemotherapy. There is apparently an increase in long-time survivors indicating the effectiveness of the chemotherapeutic scheme in use. Own results with 5 different protocols confirm this tendency. Certain cases with correlations between Ct and post mortem findings are presented. Results and conclusions are discussed. PMID- 6256979 TI - [Therapy of inflammatory and degenerative joint diseases]. PMID- 6256980 TI - [The pathogenesis of degenerative joint diseases]. PMID- 6256981 TI - [Therapeutic measures in multiple sclerosis]. PMID- 6256982 TI - The metabolism of carfecillin in rat, dog and man. AB - 1. The absorption of the phenol moiety of [phenol-14C]carfecillin following oral administration to rat, dog and man was extensive, since 95%, 73% and 99% of the administered radioactivity respectively was recovered in the urine. In contrast, less than half of the carbenicillin moiety of carfecillin was absorbed after oral administration, as judged by excretion studies using [carbenicillin 14C]carfecillin in intact and bile-duct cannulated animals. 2. The patterns of radiometabolites in the urines of rat, dog and man following single oral administration of [phenol-14C]carfecillin were determined by chromatography and radioassay. In two men, the majority of a dose was excreted as phenylsulphate (71%) and phenylglucuronide (16%) with the sulphate and glucuronic acid conjugates of quinol representing small amounts of the urinary radioactivity. Similar metabolic patterns were observed in the rat and dog following oral administration of either [14C]phenol or [phenol-14C]carfecillin, although some saturation of sulphate conjugation was apparent at the dose levels employed. PMID- 6256983 TI - [The double-pentagastrin test for measuring the gastric secretory capacity in patients of an advanced or great age (author's transl)]. AB - For studying the changes in the gastric secretory capacity that are caused by old age, the double-pentagastrin test is recommended; this test serves to examine the gastric secretory reaction by administering twice pentagastrin in a dose of 6 micrograms/kg. With this suggested method it was possible to find out the age dependent decrease in the functional possibilities of the gastric secretory system. It is demonstrated that these possibilities are determined by the physiological changes in the gastric secretory system and by the peculiarities of its neurohumoral regulation. Observations indicate an increasing sensitivity, with advancing years, of the secretory cells with respect to pentagastrin and a faster exhaustibility of the gastric secretory reaction if stimulated by pentagastrin. PMID- 6256984 TI - [Platelet sensitivity to prostacyclin in diabetic and nondiabetic patients with atherosclerotic vascular changes: a measure of platelet membrane prostacyclin receptors?]. PMID- 6256985 TI - [Ultrastructural changes in venous angiodysplasia of the Klippel-Trenaunay type]. PMID- 6256986 TI - [Congenital digital syndactylia (author's transl)]. AB - Congenital syndactylia of the fingers are discussed and the differential diagnosis is presented. While correction may be required for functional or easthetic purposes, the age of 4-6 years is recommended as the optimum time for correction. Early surgical treatment may be needed in cases of Apert's syndrome and in the case of congenital annular scars (amniotic bands). The operative technique is carefully described and general anaesthesia and exsanguination is recommended. Post-operative management is of equal importance and the fingers are dressed with vaseline gauze and a compression bandage. The author's experience is limited to 65 syndactylia operations and in only 3 of these was a repeat procedure necessary. PMID- 6256987 TI - [Syndactylia recurrences and their treatment (author's transl)]. AB - Recurrences following correction of syndactylia are usually the result of inappropriate skin incisions, or of delayed wound healing. These recurrences are examplified by interdigital cutaneous and scar bridges which may result in contractures of even rotational deformities as the result of growth. Early and late syndactylia recurrences can be differentiated. Early operative treatment is recommended and splints and bandages or similar conservative measures are useless. Considerable experience, suitable instruments and adequate surgical technique are required for these corrections. PMID- 6256988 TI - [long term results following surgical correction of syndactylia (author's transl)]. AB - Pateients were observed over a period of 10-25 years following surgical correction of syndactylia. None showed any disturbances due to growth. The interdigital webs were constructed, using a dorsal and a palmer skin-flap in each. The sides of the fingers were closed with several full-thickness skin grafts, laid horizontally and separated from each other by a skin-bridge. The results agree with previous studies. PMID- 6256989 TI - [Pitfalls in surgery of syndactylism (author's transl)]. AB - 47 children with syndactylia treated over a 12-year period were presented. The multiple Z incision with pedicle flaps is advocated. PMID- 6256990 TI - [Staged surgical correction of symbrachydactylism (author's transl)]. AB - A 3 year old girl is presented with a unilateral symbrachydactylism. A follow-up period of two years showed a satisfactory functional and cosmetic appearance, but the radiological picture of the carpal and metcarpal bones remained abnormal. PMID- 6256991 TI - [Malformation syndrome with constriction rings, pseudoligaments, acral defects and syndactylism: diagnosis and treatment (author's transl)]. AB - Congenital constricting bands of the extremities, pseudo-ligaments, distal defects of fingers and syndacatyly are all characteristic marks of this syndrome. At least two of the features must be present to make the diagnosis. The authors' results are reported and experience in paediatric hand surgery is essential. This should be performed as early as possible. Operative techniques are described. PMID- 6256993 TI - [Course of prostate cancer]. AB - From the epicritical comparison of 85 histologically ascertained carcinomas of the prostate in the 10-year interval and 105 cases in the 5-year interval in the own clinic result survival times of on an average 2.7 years or absolutely of 19.5%. References to the improvement of the prognosis in early recognition, radical operation and chemotherapeutic treatment are given. PMID- 6256992 TI - [Fiber and nutritional content of infant food]. AB - 50 mothers with healthy, already weaned babies of between 6 and 9 months old took part of the study. The babies consumed 7.5 g of dietary fibre per 1000 calories daily. The sources of energy ratio showed a definite trend in favour of carbohydrates. The proportion of sodium was extremely high. The supply of iron proved to be greatly deficient. PMID- 6256994 TI - Detection of polyphosphates and enzymes of polyphosphate metabolism in Bdellovibrio bacteriovorus. AB - Bdellovibrio bacteriovorus cells, parasitizing in E. coli, contain a considerable amount of inorganic polyphosphates, 55% of the total pool of which is due to the most polymeric acid-insoluble polyphosphates. B. bacteriovorus contains enzymes participating both in the synthesis and consumption of polyphosphates, i.e. 1,3 diphosphoglycerate: polyphosphate phosphotransferase, polyphosphate glucokinase, polyphosphatase, tripolyphosphatase, pyrophosphatase, acid and alkaline phosphatases. The possible role of high-molecular polyphosphates in the vital activity of the bacterial parasite B. bacteriovorus is discussed. PMID- 6256995 TI - Host influence on the density of chlamydiae in Renografin gradients. AB - Egg-grown and L cell-grown C. psittaci 6BC strains formed two bands when centrifuged through preformed Renografin gradients. No additional bands were observed by extending the time of centrifugation. Particles present in the bands which were collected from the Renografin gradients were examined by electron microscopy. Purified elementary bodies from both egg- and L cell-grown sources were located in a lower, minor bind; egg-derived elementary bodies showed a higher density (p < 0.01) than elementary bodies derived from L cells. Particles present in the major, upper band of both egg- and L cell-derived strains had similar densities and contained mixed populations of elementary bodies and polymorphic reticulate bodies. PMID- 6256996 TI - [Studies on the activity of the aryl hydrocarbon hydroxylase and metabolism of benzo(a)pyrene in cell strains and cell lines used for testing cytotoxic and transforming ability of foreign compounds (author's transl)]. AB - The activity of the AHH and the formation of polar metabolites from BaP was examined in several cell strains and lines, which are used for testing cytotoxic and transforming activity of environmental agents, the highest activity of the AHH and the highest capacity to metabolize BaP was found in hamster kidney cells. Much lower values were measured in kidney cells from Cercopithecus aethiops, BHK21/C13 cells, and SV-40 transformed hamster kidney cells (14-1b). The activity of AHH was inducible by BA in all these cells. However no correlation could be established between the increase in AHH activity and the formation of polar metabolites. In cells derived from a human bronchial carcinoma (E-14), a very low BaP metabolism was detectable which increased 3-fold after exposure (o BA. No BaP metabolism could be detected in HeLa cells. PMID- 6256997 TI - [Microbial settlement of paint- and building-materials in the sphere of drinking water. 5. Communication: Macrocolonies on the cement mortar lining in a water main (author's transl)]. AB - It is reported a microbial growth in form of macrocolonies on a cement mortar line in a potable water main. Simultaneously an increase of bacterial content in the water could be observed. The bacterial content could be reduced by chlorination, but the microbial growth on the surface of the lining was not suppressed. Macrocolonies could be observed the same as before at the last inspection 6 1/2 years after opening of the main. PMID- 6256999 TI - [Results obtained from staining lymphography, using carbon with lipoidal suspension, in cases of female genital carcinoma (author's transl)]. AB - Reported in this paper is the use of a carbon-lipoidal suspension for presurgical staining lymphography which was applied to carcinomata colli uteri and corporis uteri. The suspension could not be prepared until permission had been obtained from the National Drug Expert Committee. Better colour contrast representation of the femoral and iliacal lymph nodes during the operation was thus achieved, and, consequently, surgical radicality was substantively improved. The approach proved less expensive and tedious than previous methods used for colour representation of lymph nodes in the minor pelvis. The dye used did not cause any complications. The advantages of the method are discussed. General application seems to be commendable, following further testing. PMID- 6256998 TI - [Androblastoma between two normal pregnancies (author's transl)]. AB - Reported in this paper is a case of androblastoma of the right ovary, four years from first parturition. Signs of virilisation developed concomitantly but faded away very soon after tumour extirpation. The second birth took place, less than four years later. No symptoms so far have been recordable in two-a-half year follow-up checks. PMID- 6257000 TI - Level of cyclic AMP and adenyl cyclase in rabbit mammary gland during the lactation cycle. PMID- 6257002 TI - [Effectiveness of para-immunization for the control of piglet breeding losses and enzootic pneumonia of swine (piglet influenza)]. PMID- 6257001 TI - Studies on bovine leukosis. VIII. The serologic response on leucotic cattle to injections with Aujeszky's disease and Bordetella vaccines, tetanus toxoid and porcine erythrocytes. The cutaneous reaction following administration of Mycobacterium microti and the effect of pokeweed and phytohaemagglutinin stimulation on leucotic lymphocytes. PMID- 6257003 TI - [Clinical aspects of the pathology of neuromuscular transmission]. AB - On the basis of analyzing clinical reports, the results of the author's own studies, and respective information published in literature, principal problems concerning the clinical course, the mechanism of development, the methods of treatment and organization of the therapeutic and prophylactic aid to patients with neuromuscular transmission pathologies are discussed. The main myasthenic syndromes, as well as problems of myasthenia differential diagnosis are described. A question on the role of autoimmune disturbances in the formation of muscular disturbances in cases of a neuromuscular transmission pathology is raised. Data characterizing the role of anticholinesterase drugs, hormones, surgical and radiotherapeutic methods in the treatment of myasthenia and myasthenic disturbances are presented. PMID- 6257004 TI - [Defects in the cyclic adenosine monophosphate system--new hypothesis for the etiology and development of the myodystrophic process]. AB - The role of the cyclic nucleotides in the development of myodystrophic process is demonstrated. It has been shown that in patients with X-chromosome-linked myopathies the metabolic defect is localized at the level of adenylcyclase (AC): this leads to a drop of the content of cyclic adenosine monophosphate (cAMP) in the muscular tissue below the threshold magnitudes of activation of protein kinases (PKs). Indications of the primary character of those changes are: absence of relationship between the degree of the enzyme activity disturbance and the disease stage; discovery of this defect in heterozygotic carriers and systemic character of the AC complex affection. In cases of autosomal myodystrophies the primary defect of the mutant gene manifests itself in an imitation of a rise of the cAMP level because of the structural peculiarities of PKs. The data obtained were used as the basis for developing an essentially new method of treating autosomal forms of neuromuscular diseases. PMID- 6257005 TI - Corticotrophin, growth hormone and prolactin deficiencies with hypoaldosteronism and corticosteroid-reversible hypothyroidism in Sheehan's syndrome. Clinical and anatomical correlations. AB - Deficiencies of corticotrophin (ACTH), growth hormone, and prolactin were documented in a woman with diabetes mellitus and Sheehan's syndrome. The patient's ACTH deficit appeared to be secondary to a hypothalamic abnormality since on two occasions the patient had a marked plasma ACTH response to vasopressin but not to insulin induced hypoglycaemia. It is postulated that the deficits of these three adenohypophysial hormones were instrumental in causing a severely impaired aldosterone secretory capacity in response to sodium restriction and an angiotensin infusion. In addition, the patient had an unusual form of thyroid dysfunction that was in part reversed with hydrocortisone replacement. The patient's unfortunate death during a hypoglycaemic crisis allowed correlation between her extensive antemortum endocrine testing and her pathologic anatomy. PMID- 6257006 TI - 'Proopiocortin fragments' in normal human adult pituitary. Distribution and ultrastructural characterization of immunoreactive cells. AB - The distribution and ultrastructure of cells immunoreactive towards antisera against synthetic fragments of proopiocortin were studied in human pituitaries by immunohistochemical methods. Anterior lobe cells exhibiting the ultrastructural characteristics of corticolipotropes, as well as all epithelial cells 'invading' the posterior lobe, display beta-endorphin/beta-lipotropin-ACTH immunoreactivities. At low dilution a beta-lipotropin antiserum, raised with highly purified antigen, stains also somatotropes. alpha-MSH antibodies bind to certain corticolipotropic cells in the pars distalis and to only a few of the cells 'invading' the pars nervosa. Met-enkephalin antisera react only with isolated cells in the anterior lobe. These results indicate a striking difference in the processing of the proopiocortin precursor molecule in different corticolipotropic cells of the human hypophysis. Furthermore, the hypothesis of a homology between cells 'invading' the human neurohypophysis and those of the intermediate lobe of lower vertebrates, is questioned. PMID- 6257007 TI - Adrenocortical function in idiopathic haemochromatosis. AB - In idiopathic haemochromatosis, excessive iron deposits include adrenal cortex, and mainly the zona glomerulosa. In this view, we measured basal and post stimulative values of plasma cortisol, aldosterone and renin activity (RA) in two groups of patients: 1) 9 normal-salt repleted subjects (NSR) who were subjected to iv ACTH and furosemide tests, 2) 10 patients who were subjected to chronic salt depletion (CSD), to iv ACTH and furosemide tests. The results were compared with two groups of 7 healthy volunteers (NSR and CSD). In the patients, basal cortisol values were either normal or increased in cases of poorly controlled diabetes (21 +/- 2.1 microgram/100 ml, P < 0.01) and cortisol increase after ACTH injection was normal (to 43.3 +/- 4.3 microgram/100 ml). In the 9 NSR patients, basal aldosterone (7.75 +/- 1.5 ng/100 ml) and RA (1.55 +/- 0.27 ng/ml/h) values were normal; aldosterone and RA rose after furosemide injection: these increases were similar in these patients (respectively to: 13.5 +/- 2.2 ng/100 ml and 4.3 +/- 0.6 ng/ml/h) and in the 7 NSR controls. In the 10 CSD patients, basal aldosterone and RA values were always increased (26.5 +/- 3.2 ng/100 ml and 8.5 +/- 2.3 ng/ml/h) as much as in the 7 CSD controls. After ACTH administration, aldosterone values (26.1 +/- 4 in NSR patients, 54 +/- 8 ng/100 ml in CSD patients) were the same as in the two control groups. This study suggests that there is no adrenocortical deficiency in idiopathic haemochromatosis, in spite of excessive iron deposits in the adrenal cortex. PMID- 6257008 TI - Discrepancy between the effects of desialylation of human chorionic gonadotrophin on in vitro ovarian biological activity and on receptor binding. AB - An in vitro bioassay based on progesterone production by enzymatically-dispersed immature rat ovary cells, was used to investigate the effect of sialidase treatment on the biological activity of human chorionic gonadotrophin (hCG). The potency in this bioassay system and in an ovarian receptor assay were compared, to substantiate possible discrepancies between the effect of this treatment on biological activity and on receptor binding. Ovarian cells responded dose dependently to the addition of hCG as well as sialidase treated hCG (asialo-hCG). Dose-response curves of hCG and asialo-hCG were parallel and the maximal stimulation levels reached were the same. Sub-maximal doses of hCG and asialo-hCG were additive. The potency of asialo-hCG was 65% of the original preparation. Addition of low concentrations of phosphodiesterase inhibitor resulted in a greatly enhanced sensitivity of the bioassay, but had no effect on the potencies of asialo-hCG and hCG. In contrast to intact gonadotrophins, the receptor assay potency of asialo-hCG was more than three times the bioassay potency. In agreement with this, it was found that when equal amounts of 125I-labelled hCG and asialo-hCG were specifically bound to the ovarian cells, the latter stimulated progesterone production less effectively. It is concluded that there is a discrepancy between the effect of desialylation on the biological activity and on the receptor-binding ability of hCG. PMID- 6257009 TI - Inhibition of LH-stimulated cyclic AMP formation in pre-ovulatory rat granulosa cells by follicular fluid. AB - Immature female rats were injected sc with a single dose of PMSG to induce growth and maturation of ovarian follicles. In the morning of prooestrus the rats were given a single ip injection of LH (10 micrograms/rat) or 0.154 M NaCl, 2 h prior to sacrifice. Granulosa cells were isolated fro the pre-ovulatory follicles and incubated in Krebs bicarbonate buffer, for 1 h with or without in vitro addition of various test substances. Following incubation the amounts of cAMP in tissue plus medium were determined. It was found that the isolated granulose cells exposed to LH in vivo responded to the addition of LH in vitro with a production of high amounts of cAMP, i.e. these cells were not refractory to LH stimulation and in fact responded better than granulosa cells isolated from ovaries not exposed to LH in vivo. The addition to the incubation medium of follicular fluid (FFl) obtained from pre-ovulatory follicles decreased the effect of LH in vitro when added at a final concentration of 1% and completely abolished it at a concentration of 3%. Removal of steroids from the FFl did not influence the inhibitory effect and the addition of a phosphodiesterase inhibitor (IBMX) in vitro did not alter the results in principle. These results point to the existence of a factor in the FFl which interacts with the sensitivity of the isolated pre-ovulatory granulosa cells to repeated exposures to LH. Characterization of this factor is subject to further investigations. PMID- 6257010 TI - Effect of neonatal hypothyroidism on maturation of nuclear triiodothyronine (T3) receptors in developing rat brain. AB - Changes of nuclear T3 receptors during brain maturation were studied in normal and hypothyroid rats. In normal rats, the higher receptor concentration present in the neonatal period (0.35 +/- 0.04 ng T3/mg DNA) decreased at the age of 14 days (0.25 +/- 0.02 ng T3/mg DNA), and remained at this level thereafter to 35 days of age (0.25 +/- 0.03 T3/mg DNA). In contrast, hypothyroid rats showed a significantly higher concentration than that found in an age-matched control group at the age of 14 days (0.38 +/- 0.07 ng T3/mg DNA), and maintained this level up to 35 days of age (0.37 +/- 0.03 T3/mg DNA). The binding affinity was similar in both groups and throughout maturation (mean +/- SD in normal groups; 1.9 +/- 0.3 X 10(10)M-1, in hypothyroid groups: 1.7 +/- 0.2 X 10(10)M-1). Plasma T3 concentrations showed changes reciprocal to those in the binding capacity of T3 receptors. These results indicate that nuclear T3 receptors in rat brain mature by the age of 14 days, in association with a decrease in binding capacity, and this process seems to be T3-dependent. The physiological role of the high concentration of T3 receptors observed in neonatal and hypothyroid rat brain during development is at present not clear. PMID- 6257011 TI - Corticotropin- and lysine-vasopressin induced changes of plasma corticosteroids and testosterone in the adult male pig. AB - Intravenous injection of 10.0 micrograms/kg body weight synthetic corticotropin (1-24 ACTH) into chronically cannulated boars resulted in significantly elevated plasma corticosteroid and testosterone levels between 20 and 140 min (corticosteroids) and 20--80 min (testosterone) after injection. Administration of lysine-vasopressin (LVP) at doses of 0.1, 0.2 and 0.4 IU/kg body weight elicited a significant increase of plasma corticosteroids between 20 and 40 min after injection; on the other hand, plasma testosterone concentrations tended to fall when compared to pre-treatment levels. From our results it can be concluded that exogenously applied ACTH can effectively stimulate the release of corticosteroids and testosterone. Intravenous administration of LVP results in significantly, although not maximally increased plasma corticosteroid concentrations; the release of endogenous ACTH induced by LVP injection, on the other hand, appeared to be too small to stimulate testosterone release significantly. PMID- 6257013 TI - Quantitative studies of vasoactive intestinal peptide (VIP) binding sites and VIP induced adenosine 3':5'-monophosphate production in epithelial cells from duodenum, jejunum, ileum, cecum, colon and rectum in the rat. AB - The binding of vasoactive intestinal peptide (VIP) and its effect on adenosine 3':5'-monophosphate (cyclic AMP) production were measured in isolated rat intestinal epithelial cells from duodenum, jejunum ileum, cecum, colon and rectum. In every segment tested, VIP binding and VIP-induced cyclic AMP production exhibited a similar pattern with two populations of VIP binding sites and similar magnitude of cyclic AMP production. Continuous displacement of the binding of 125I-labelled VIP and stimulation of cyclic AMP production were observed in the range of 10(-10)--10(-7) M VIP concentrations. Fifty per cent inhibition of the initial binding of tracer was obtained with 2.2 to 3.2 nM VIP. The Km of stimulation of cyclic AMP production was 1.2 to 2.6 nM VIP. Chicken VIP and porcine secretin showed a 4-fold higher and a 100-fold lower affinity than porcine VIP for binding sites, respectively. The same was true for the stimulation of cyclic AMP production. The existence of receptors highly sensitive to VIP in the separate segments of the bowel corresponds to the presence of high concentration of VIP at the vicinity of epithelial cells and strongly suggests that VIP is active in regulating different intestinal functions. PMID- 6257012 TI - Adrenal corticosteroids and immunoreactive ACTH in chronically cannulated ovine foetuses with bilateral adrenalectomy. PMID- 6257014 TI - Congenital adrenal hyperplasia due to partial 21-hydroxylase deficiency. A study of five cases. PMID- 6257015 TI - Effect of cyproterone acetate on pituitary-adrenocortical function in man. AB - Recent literature (1973-1976) suggests suppression of pituitary-adrenal function in patients (eg with pubertas praecox) who are treated with cyproterone acetate in high doses for prolonged periods. Therefore we investigated in our metabolic ward the effects of administration of 200 mg cyproterone acetate per day during 20 days to 4 healthy male volunteers. Baseline plasma cortisol and ACTH levels, repeated diurnal plasma cortisol and ACTH profiles and the results of tetracosactide (Synacthen) stimulation tests and single-dose metyrapone (Metopiron) tests proved to be comparable before, during and after treatment. Moreover, a slight gradual increase in urinary cortisol excretion during the observation period indicated that cyproterone acetate in the given dose during 20 days certainly does not reduce the pituitary-adrenal function of 4 healthy male volunteers. Long-term administration (during 1 to 7 years) of the combination of cyproterone acetate and ethinyloestradiol did not suppress serum levels of cortisol, prolactin, thyroxine and TSH in 18 female patients with hirsutism and/or acne. PMID- 6257016 TI - Plasma pattern of immunoreactive ACTH in normal man and in patients with Nelson's syndrome. AB - A radioimmunoassay for ACTH determinations in human plasma was developed using an N-terminal antiserum. Plasma ACTH levels at 6 a.m. in 39 patients with normal pituitary-adrenal function were below 4 pmol/l in two individuals. The remaining had a mean of 32.7 +/- 4 pmol/l (n = 37). Gel filtration on Sephadex G-50 medium and G-75 revealed that a high molecular weight immunoreactive ACTH was found in plasma from both normal individuals and patients with Nelson's syndrome. The stimulation of ACTH secretion with metyrapone (750 mg perorally) significantly increased the mean plasma levels of 1-39 ACTH after 3 h (from 0.9 to 6.6 pmol/l) in 10 healthy individuals. The level of the high molecular weight form remained constant. In one patient with Nelson's syndrome hydrocortisone iv (100 mg/h for 3 h) suppressed the total ACTH levels from 360 to 83 pmol/l following corticoid withdrawal on the previous evening, but did not affect the high molecular weight form of ACTH. The difference between the amounts of immunoreactive ACTH found in plasma from normal individuals and from patients with Nelson's syndrome was attributed to 1-39 ACTH. PMID- 6257017 TI - New aspects of the physiological significance of LRH receptors of pituitary plasma membranes. PMID- 6257018 TI - Thyroid hormone regulation of the catecholamine effects in human adipose tissue. AB - The possibility of a relationship between the thyroid hormone level and the peripheral action of catecholamines was examined in 4 normal-weight and 19 obese euthyroid subjects as well as in 27 hyperthyroid subjects by comparing the serum thyroid hormone level and the in vitro effect of catecholamines on lipolysis and cyclic AMP accumulation in adipose tissue incubated with and without isopropyl noradrenaline (ISNA) or noradrenaline (NA). ISNA- and NA-induced rates of lipolysis and cyclic AMP production were significantly correlated with free thyroxine index (r = 0.63-0.74) and with the serum triiodothyronine level (r = 0.83-0.87). The thyroid hormone level was neither correlated with basal rate of lipolysis nor with basal cyclic AMP production (r < 0.2). These results suggest that the magnitude of catecholamine-induced cyclic AMP production by peripheral cells may be regulated by the level of circulating thyroid hormones. The effect of thyroid hormones on lipolysis appears to be specifically linked to the action of catecholamines. PMID- 6257019 TI - [The various causative agents of viral hepatitis]. PMID- 6257020 TI - [Benign hepatic tumours and oral contraception. Pathophysiology (author's transl)]. PMID- 6257021 TI - [Pathological study of a surgical series of benign tumoral lesions of the liver (author's transl)]. PMID- 6257022 TI - [Localised hepatic tumours (author's transl)]. PMID- 6257023 TI - Clinical effects of a new TENS using multiple electrodes and constant energy. PMID- 6257024 TI - [Minimal encephalitis in patients with renal transplant. Clinicopathological study and discussion of the role of the cytomegalovirus (author's transl)]. AB - An autopsy was performed in ten patients recipients of renal allograft who died from cytomegalovirus pulmonary infection. In six patients, encephalitis lesions disseminated in the whole brain were observed. These lesions were not symptomatic. The particular features of this entity and its relationships with the type of immunosuppression therapy are discussed. PMID- 6257025 TI - Liver cell carcinoma in young women possibly induced by oral contraceptives. AB - Two cases of liver cell carcinoma in young women ingesting oral contraceptives have been found within a few months in the county of Vejle, Denmark. Including these two patients 22 cases of liver cell carcinoma in young women have been published since 1973, 19 of whom have used oral contraception. The possible effects of oral contraceptives in inducing liver tumors is discussed, and it is pointed out that no statistical proof of such an effect exists at present. PMID- 6257026 TI - Medication behaviour. A study of outpatients treated with pilocarpine eye drops for primary open-angle glaucoma. PMID- 6257027 TI - Response of human corneal endothelial cells to increased intraocular pressure. PMID- 6257028 TI - The influence of antifibrinolytica on traumatic hyphaema and corneal oedema. PMID- 6257029 TI - Glomus tumor. PMID- 6257030 TI - [The immuno-pharmacology of flores Gonatanthus pumilus (author's transl)]. PMID- 6257031 TI - [Dimercaptosuccinic acid per os promoted the excretions of Pb, Cu, Sb, Sr, Tl and Pm (author's transl)]. PMID- 6257032 TI - Selective phlebography in pancreatic and peripancreatic disease. AB - Pancreatic phlebography was performed in 67 patients with proven inflammatory or tumour disease in the region of the pancreas. The findings are described and the diagnostic value of the method is discussed. PMID- 6257033 TI - Granulosa- and theca-cell tumors. Incidence and occurrence of second primary tumors. AB - An analysis of 936 women with granulosa- and theca-cell tumors reported to the Swedish Cancer Registry between 1958 and 1972 showed crude annual incidence rates for these lesions of 0.72 and 0.74, respectively, pre 100 000 of the female population, unchanged during the period. The age-specific incidence rates, both groups taken together, increased almost linearly from 35 to 69 years. The women displayed an increased risk of developing endometrial carcinoma and malignant lymphoma, possibly also breast, colon and thyroid carcinoma. PMID- 6257034 TI - Prolactin-secreting pituitary adenoma. Observations in irradiated patients. AB - Six women with clinical, biochemical and radiologic evidence of a prolactin secreting pituitary adenoma were irradiated with 50 Gy in 5 1/2 weeks. In 3 of the 6 patients, irradiation preceding maintenance bromocriptine medication was followed by a normalization of serum prolactin levels which resulted in a normal pregnancy in 2 and reestablishment of the menstrual cycle in the third. In 5 of 6 patients serum prolactin was substantially reduced by the end of the treatment, but without reaching normal levels, although no correlation was found between the degree of this decrease and the clinical result. PMID- 6257035 TI - Primary mucosal malignant melanoma. Appraisal of role of radiation therapy. AB - Primary malignant melanoma of the vagina and esophagus are reported and the literature on the subject is extensively reviewed. The role of large fraction irradiation is appraised. In both cases, no exenterative surgery was imposed but instead, intermittent large fraction irradiation with protracted high doses was elected for local control. PMID- 6257036 TI - Hodgkin's disease, clinical stages I and II. Results of radical irradiation with or without chemotherapy. AB - From 1965 to 1976, 170 patients with Hodgkin's disease, clinical stages I or II, were treated with radical irradiation. A first group of 42 patients was treated with irradiation alone, a second group of 24 patients received one course of chemotherapy followed by irradiation, and a third group of 104 patients was treated with a sandwich regimen including chemotherapy + irradiation + chemotherapy. Although the treatment were not randomized, the comparison of the results shows a striking improvement in the group submitted to the C + R + C regimen: in this group the plateau of disease-free survival was 90 per cent. This result was obtained after treatment for about 3 months without surgical staging or maintenance chemotherapy. However, this treatment may favor some complications,. mainly the development of a second malignancy; these risks may be decreased by reducing the treatment in patients with good prognosis. PMID- 6257037 TI - Chloramphenicol toxicity in radiation disease. AB - The effect of chloramphenicol given in high therapeutic doses, in the course of postirradiation syndrome in irradiated mice of C57Bl/10 strain, is reported. Chloramphenicol treatment increased postirradiation mortality of animals and intensified suppression of the proliferating and differentiating processes in hemopoietic organs of the irradiated animals. The results support the assumption that postirradiation depression of hemopoiesis is a contraindication to the therapeutic employment of this antibiotic. PMID- 6257038 TI - Collimation of high energy electron beams. AB - The collimation of high energy electron beams for radiation therapy is treated with special attention on the contamination of the beam by electrons which ideally should be stopped, but instead are scattered back into the beam through the edge of the collimator. It is demonstrated that the mean energy of these electrons is only 40 per cent of the mean energy in the beam and that the smallest electron contamination is obtained if the material closest to the beam is of high density. PMID- 6257039 TI - Microdosimetry. II. Use of secondary electron emission to simulate two target models. AB - A potential technique to analyse related energy depositions in two adjacent tissue-equivalent volumes is described. The technique is based on secondary electron emission from the two surfaces of a micrometer thick foil. The foil should thus simulate two nm thick slabs separated a distance equal to the thickness of the foil. Calculations of the coincident probability, i.e. the probability that any secondary electrons are emitted from the front surface when at least one secondary electron is emitted from the exit surface, is presented to show the potential of the technique. An experimental arrangement is also discussed. PMID- 6257040 TI - Chromosome counts of 90Sr-induced osteosarcomas in mice. III. Variation of the chromosome counts of in vivo transplanted tumours, in vitro cultures and retransplanted cultured cells. AB - This investigation started from serially in vivo transplanted tumours. The chromosome patterns of in vitro cultures and of parallelly and serially transplanted tumours were examined. Cultured cells were also used for retransplantation to mice. When comparing the chromosome counts of the cultured cells and the in vivo transplanted tumours, significant differences were revealed. When retransplanting cultured cells, it was also noticed that a similar chromosome distribution appeared, as previously found in 90Sr-induced transplanted series. PMID- 6257041 TI - Age and dose related carcinogenicity of 90Sr. AB - 90Sr was given at three different dose levels (29.6, 14.8 and 7.4 kBq/g b.w.) to groups of mice aged 300, 150, 75 and 25 days. It was found that the incidence of osteosarcomas was highest in the 75-day-old-group and lowest in the two oldest age groups. The frequency of lymphoreticular tumours was inversely dose-related (highest incidence in the lower dose series) and not dependent on age at the time of 90Sr injection. The frequencies of soft tissue tumours indicate that these tumours are more related to age than to the dose employed. PMID- 6257042 TI - Dose distribution around radium arrays used in the treatment of uterine carcinoma. AB - Measurements have been made to determine the dose distribution around typical arrays of commercially available Campbell type Heyman applicators using thermoluminescent dosimeters. These measurements verify the tables produced by Benner, linking the number of sources used in the so called packing technique for the treatment of uterine carcinoma to an optimum treatment time. PMID- 6257043 TI - Irradiation injury of bone tissue. A vital microscopic method. AB - A vital microscopic method using the titanium chamber for observation of bone irradiation injury in situ is described. The subsequent development of bone tissue resorption and replacement with a pathologic immature bone could be observed and recorded. PMID- 6257044 TI - Theca-cell tumors. Clinical features and prognosis. AB - During the period 1923 to 1972, 62 women with theca-cell tumors were treated at Radiumhemmet. The mean age at diagnosis was 59.5 years. Concomitant endometrial carcinoma was found in 13 patients. At 1978, after a mean observation time of 15.5 years, 30 patients were alive. No patient died from thecoma. Malignant disease caused death in 7 women. No difference in survival was found between 20 patients and 40 controls matched by age and place of residence. PMID- 6257045 TI - Sensitivity of cells in exponential and stationary growth phase to combined treatment with radiation and quinacrine. AB - The effect of Quinacrine on the recovery of cells from sublethal radiation injury was analysed by testing cellular survival after exposure to low and high radiation doses, and after irradiation with split doses. Quinacrine was found to inhibit recovery in cell cultures in exponential growth phase but not, or only slightly, in cells in stationary growth. This finding is related to the inhibitory effect of Quinacrine on the repair of radiation induced DNA strand breaks. PMID- 6257046 TI - Calcitonin and mammary carcinoma. AB - Plasma calcitonin was determined in 33 patients with breast carcinoma. Eight patients had bone metastases as revealed at scintigraphy and radiography. Only 3 of the 33 patients had elevated plasma calcitonin, 2 had osteolytic bone metastases. It is concluded that the determination of plasma calcitonin is of no value in the evaluation of patients with breast malignancy and it should not be referred to as a tumor marker. PMID- 6257047 TI - Effect of a screening programme on breast carcinoma incidence, mortality and survival. AB - Screening for breast carcinoma revealed 27 cases of malignancy, 7 of them preclinical. The method consisted of palpation and health education. Mammary radiography and fine needle biopsy were used in uncertain cases only. Shortly after the screening the incidence and mortality were lower (1.07 and 0.29 per 10(3), respectively) than during the screening (1.40 and 0.45 per 10(3)). Survival also improved and the percentage of localized cases was higher for patients diagnosed during or after screening than for patients diagnosed before. However, the changes did not show any substantial differences from the long-term trends. It was concluded that the screening programme had no real effect on the malignancy risk. The absence of effect was accounted for by the relatively inefficient screening method. PMID- 6257048 TI - Effect of single dose irradiation on the proliferation kinetics in a human malignant melanoma in athymic nude mice. AB - The effect of single dose irradiation on the proliferation kinetics in a human malignant melanoma grown in the athymic mutant nude mouse was analysed. DNA histograms were obtained with flow cytofluorometry. Percentage labelled mitoses curves were established by the use of conventional autoradiographic techniques. Changes in the fraction of clonogenic cells with time after irradiation were measured in vitro in soft agar. In non-irradiated tumours the fraction of cells in G1/G0, S and G2 + M was 66.21 and 13 per cent, respectively. The median duration of G1, S, G2, M and Te was 19.0 h, 13.3 h, 5.0 h, 1.0 h and 41.4 h, respectively. The growth fraction was calculated as 0.66 and the cell loss factor as 0.67. The growth fraction was increased after irradiation and the cell cycle time reduced, due to a shortening of G1. These effects were dose dependent and decreased with time after exposure, but were still present after the tumours had resumed a continuous volume growth. The rate of volume growth was slower for irradiated tumours than for non-irradiated tumours of the same size, due to a larger cell loss factor for the former. PMID- 6257050 TI - Chromosome counts of 90Sr-induced osteosarcomas in mice. IV. Variation of chromosome counts when using tumours of predetermined age for transplantation. AB - Transplanted tumours from a 90Sr-induced primary tumour were used as an experimental model to eliminate any connection between the chromosome distribution and outgrowth period of radiation-induced transplanted tumours. For this reason repeated transplantations were performed from different tumours of predetermined age from a transfer generation, to receive separate but parallel transfer generations. From each one of these generations a tumour of the same age as used to establish a particular generation was used for continued transplantation. It was then observed that the percentage of 40-chromosome cells in general decreased with the age of the tumour used for transplantation. Furthermore, early established transfer generations were often characterized by more slow growing tumours. However, it should be realized that even if a true relationship between chromosome pattern and outgrowth period cannot be eliminated, the differences found may be due to accidental variations. PMID- 6257049 TI - Dose effect relationships in cervical and thoracic radiation myelopathies. AB - The course and prognosis of radiation myelopathies are determined by 3 factors; the segmental (vertical) location of the lesion, the extent of the transverse syndrome (complete or incomplete) and the radiation dose. The median spinal dose in cervical radiation myelopathies with fatal outcome was higher than in survivals with an incomplete transverse syndrome. In thoracic radiation myelopathies a dose difference between complete and incomplete transverse syndromes could be found as well. Incomplete transverse syndromes as submaximum radiation injuries are more suitable for the determination of the spinal tolerance dose than complete transverse syndromes. The lowest threshold could be stated for cases following high-volume irradiation of the lymphatic system. PMID- 6257051 TI - Radiation sensitivity of DNA molecules in situ in normal and neoplastic tissues of mice. AB - The sensitivity to radiation of DNA molecules in situ in various tissues was estimated by alkaline sucrose gradient centrifugation. The sensitivity of DNA in liver, thymus, spleen and cerebellum was found to be of the same order of magnitude. The oxygen enhancement ratios of DNA in spleen, thymus and cerebellum were all approximately three. Sensitivity of DNA molecules in the tumour was about half of that in normal tissues, probably because of its hypoxicity. PMID- 6257052 TI - Induction of neoplasia by 140Ba in mice. AB - C57Bl mice of both sexes were given intraperitoneal injections of 140Ba-nitrate at 3 different dose levels (55.5, 37.0 and 18.5 kBq/g b.w.). Osteosarcomas were found in all groups and the osteoblastic type was the most common. In the middle and the highest dose groups, female mice developed tumours more frequently than the males. The irradiation doses were calculated to the femur, lumbar vertebrae and sternum and turned out to vary between 6 and 0.7 Gy. PMID- 6257053 TI - Influence of the thyroid hormones on erythropoiesis and radiation resistance in C 57 black mice. AB - Oral administration of dried thyroid gland to C57Bl adult male mice in a dose of 0.6 g per 100 g diet during 10 days increased the metabolic rate and stimulated the erythropoiesis. Three to six days after thyroid pretreatment the radiation resistance of the mice increased, as revealed by their 30-day survival and a higher recovery of peripheral blood cell counts. The period of increased resistance to radiation was correlated with the receding of hypermetabolic effects and with the increase of repopulating abilities of the bone marrow cells. PMID- 6257054 TI - Electron and photon beams from a 50 MeV racetrack microtron. AB - The quality of broad high energy photon and electron beams can be improved considerably by the scanning of elementary narrow beams. Dose distributions produced in this way have advantages with respect to improved dose gradients and therapeutic ranges for electrons and lower surface doses, increased depth doses and half value depths for photons. The possibility of giving the whole therapeutic dose in a single local pulse of short duration is discussed as a new method to protect superficial tissues. PMID- 6257055 TI - Effect of different kinds of fibre on postprandial blood glucose in insulin dependent diabetics. AB - Dietary fibre may retard glucose absorption in normal and diabetic subjects. It is, however, unclear which type of fibre would be most suitable for this purpose. We therefore studied whether pectin differs from fibre from barley (85%) and citrus (15%) (Dumovital) in its effect on postprandial blood glucose responses. Eight insulin-dependent diabetics fasted overnight and were then given a meal without their morning insulin. The basic meal, composed of 90 g white bread and 120 g jam (total carbohydrate 105 g), was given three times: alone, with 15 g pectin and with 15 g Dumovital fibre. Blood glucose was measured for three hours. The tests showed that pectin administration considerably inhibited the postprandial rise in blood glucose, while Dumovital showed no such effect. Barley/citrus fibre (a mixture of cellulose, hemicellulose, lignin and pectin) has not the same inhibiting effect on postprandial rise in blood glucose as pure pectin in insulin-dependent diabetics. Thus, the specific type of fibre must be considered when prescribing dietary fibre to diabetics. PMID- 6257056 TI - Prostaglandins and cyclic nucleotides in hypoxic myocardium. PMID- 6257057 TI - In vitro structural study of cellular populations derived from human gliomas. PMID- 6257058 TI - Spinal subarachnoid metastasis from primary intracranial gliomas. PMID- 6257059 TI - Electron spin echo spectroscopy and the study of biological structure and function. PMID- 6257060 TI - Molecular mechanism of DNA repair after ionizing radiation. PMID- 6257061 TI - GABA and benzodiazepine receptors. PMID- 6257063 TI - Demonstration and characterization of an endogenous inhibitor of GABA-enhanced [3H]-diazepam binding from bovine cerebral cortex. PMID- 6257062 TI - GABA receptors as supramolecular units. PMID- 6257064 TI - Desensitization of GABA receptors. PMID- 6257065 TI - GABA receptor associated drug receptors. PMID- 6257066 TI - GABA receptors regulate the affinities of anions required for brain specific benzodiazepine binding. PMID- 6257067 TI - Benzodiazepine receptors: autoradiographical and immunocytochemical evidence for their localization in regions of GABAergic synaptic contacts. AB - The morphological demonstration of BR in GABAergic synapses is a major step forward in the understanding of the mechanism of action of benzodiazepines. It bridges the gap between the electrophysiological evidence stressing the involvement of GABAergic synaptic transmission in the action of benzodiazepines, and the biochemical evidence stressing BR as the site of action for this group of drugs. At present we do not know in which types of synapses those BR are localized which were not associated with GAD positive terminals. At least some of the silver grains may nevertheless be localized in GABAergic terminals, since probably not all GABAergic terminals were stained immunocytochemically. However, it is also possible that some BR are localized in non-GABAergic synaptic contact regions. This possibility would open new concepts for our understanding of the mechanism of action of benzodiazepines and is presently under experimental investigation. PMID- 6257068 TI - beta-Carboline-3-carboxylates and benzodiazepine receptors. PMID- 6257069 TI - GABA autoreceptors: structure-activity relationships for agonists. PMID- 6257071 TI - The regulation of benzodiazepine recognition sites by endogenous modulators. PMID- 6257070 TI - Role of membrane lipids on the regulation of GABA recognition sites. PMID- 6257072 TI - Barbiturates and GABA receptors. PMID- 6257073 TI - The role of GABA mediated neurotransmission in convulsive states. PMID- 6257074 TI - GABA-agonists as anti-epileptic agents. PMID- 6257075 TI - Positron tomography. A new method for in vivo brain studies of benzodiazepine, in animal and in man. PMID- 6257076 TI - Localization of GABA and dopamine receptor sites in retinal glial cells using DL alpha-aminoadipic acid. PMID- 6257077 TI - Radiohistochemical studies of benzodiazepine and GABA receptors and their interactions. PMID- 6257078 TI - GABA and benzodiazepine receptors. Studies on their localization in the hippocampus and their interaction with central dopamine neurons in the rat brain. PMID- 6257079 TI - Benzodiazepine binding sites: properties and modulation. PMID- 6257080 TI - Convulsant and anticonvulsant drug binding sites related to GABA-regulated chloride ion channels. PMID- 6257081 TI - The oncogenic function of mammalian sarcoma viruses. PMID- 6257082 TI - Ectopic hormone production viewed as an abnormality in regulation of gene expression. PMID- 6257083 TI - The role of viruses in human tumors. PMID- 6257084 TI - Biochemistry of experimental ischemic brain edema. PMID- 6257085 TI - Role of dibutyryl cyclic adenosine 3',5'-monophosphate in the genesis of brain edema. PMID- 6257086 TI - Pathophysiology of the nucleus in brain edema. PMID- 6257087 TI - A central neuroendocrine system regulating brain volume. PMID- 6257088 TI - Bovine lymphosarcoma. PMID- 6257089 TI - [Gingival granular cell tumor or congenital epulis?]. PMID- 6257090 TI - [Mixed brachiogenic tumor or mixed parotid tumor?]. PMID- 6257091 TI - [Abrikosov's tumor of the cheek bone: apropos of a case]. PMID- 6257092 TI - Contribution of CT to quantitative radiation therapy planning. AB - The contribution of computed tomography (CT) in radiotherapeutic treatment of lung cancer was evaluated. Radiation therapy ports prepared for 50 patients on the basis of routine diagnostic radiographs and without CT scan information were reviewed after CT scanning. Of 50 patients, 13 (26%) required alteration of treatment ports on the basis of the additional CT scan information. In 11 patients (22%) the changes resulted in an increase in field size to cover the tumor adequately, and in two patients (4%-) the field size was reduced to spare normal tissue. A three-phase study was completed to evaluate the impact of CT on quantitative parameters of two-dimensional treatment plans on 25 of the 50 patients. Treatment plans in the absence of CT scan and without lung transmission correction were compared with treatment plans where CT information was used and lung transmission corrections were performed. Numerical results for local efficiency and nonuniformity factor were compared for conventional, CT unoptimized, and CT optimized plans. Of the 25 patients, 14 (56%) had poorer local efficiency and 16 (64%) had nonuniformity factor exceeding 5% when treatment was planned without CT information. CT-optimized plans improved local efficiency in 16 (64%) of 25 patients and reduced nonuniformity to within 5% in 21 (84%). It is suggested that in the treatment planning of patients with lung cancer, CT scan information is essential for accurate determination of dose distribution and optimization of therapy. PMID- 6257093 TI - Circumscribing or periadenomal vessel: a helpful angiographic finding in certain islet cell and parathyroid adenomas. AB - Angiographic visualization of a vein or artery partly or completely encircling small adenomas of islet cell or parathyroid origin is an occasional helpful localizing sign, particularly when the overlying pancreas or thyroid glands are intensely stained. Three examples (two islet cell; one parathyroid) are presented. PMID- 6257094 TI - CT approach to benign nasopharyngeal masses. AB - The physical characteristics of the fascial planes of the nasopharynx provide a basis for categorizing growth patterns of the more common benign nasopharyngeal masses. Lymphoid hyperplasias are confined to the surface by the very dense pharyngobasilar fascia that lies beneath the submucosa. It takes a very aggressive process to cross this fascial plane. More laterally throughout the paranasopharyngeal space the loose areolar nature of the buccopharyngeal fascia permits benign tumors in this space to assume a spherical configuration. The carotid sheath is also a loose areolar arrangement that permits free movement of the carotid artery in the neck. Juvenile angiofibromas permeate natural foramina, displace bony septa, and extend widely but do not invade the carotid sheath. Neurogenic tumors and paragangliomas are intimately associated with contents of the carotid sheath; therefore, they obliterate the low density regions surrounding the carotid vessels. PMID- 6257095 TI - Mesoblastic nephroma: radiologic-pathologic correlation of 20 cases. AB - The mesoblastic nephroma is a benign renal tumor that usually appears as a neonatal abdominal mass. The tumor is composed of connective tissue that grows between nephrons and usually replaces most of the renal parenchyma. Radiographic and sonographic images reflect this cellular composition and unique growth pattern. The radiographs of 20 cases of mesoblastic nephroma were correlated with their pathologic findings and are described. Urograms usually demonstrate an intrarenal mass two to seven times larger than the contralateral kidney. Contrast medium is occasionally demonstrated within the tumor and may represent function by nephrons trapped within the mesoblastic nephroma. Sonographic studies correlate well with the gross morphology and may be useful in establishing the relation of the tumor to the kidney. Some neovascularity is present on angiographic examination and most tumors are hypervascular. Prognosis after complete excision is excellent and adjunctive therapy is unnecessary. PMID- 6257096 TI - Neoplastic-induced renal vein enlargement: sonographic detection. AB - Five patients with sonographic evidence of a dilated renal vein are described. The etiology of the dilated renal vein was tumor thrombus in two patients, neoplastic arteriovenous shunting in two, and portal systemic shunting into the left renal vein in one. Tumor thrombus had echogenic enlargement of the renal vein, whereas anechoic enlargement of the renal vein was secondary to increased blood flow within the renal vein. Portorenal shunting can be differentiated from a neoplastic renal arteriovenous fistula by the presence of thrombus within the portal system and the absence of a renal mass. Pitfalls in the diagnosis of renal vein enlargement are discussed. PMID- 6257097 TI - Eye cytology. AB - Scrapings of the conjunctiva should be obtained as part of the evaluation of the inflamed eye. Conjunctival specimens are obtained by a simple technique using readily available materials. Anesthesia is usually not required. Viral or fungal elements, as well as bacteria, can be identified. Cytologic studies reveal the character of exudates and premalignant or malignant lesions. Adenovirus and herpes simplex produce characteristic cellular changes and inclusion bodies. PMID- 6257098 TI - Topical antibiotics and minor skin trauma. AB - Recent double-blind controlled studies show that the application of a neomycin bacitracin-polymyxin preparation reduces the incidence of staphylococcal and streptococcal infection of minor skin trauma. Allergic sensitization to neomycin is rare. Systemic side effects occur only with improper massive exposure. Resistant strains have appeared only in "closed populations." It is concluded that topical antibiotic combinations are safe and effective. PMID- 6257099 TI - Drug therapy of peripheral neuropathy. PMID- 6257100 TI - Efficacy of oral angiotensin-converting enzyme inhibition with captopril therapy in severe chronic normotensive congestive heart failure. AB - To evaluate the therapeutic efficacy of oral angiotensin-converting inhibition (ACE) with captopril in chronic normotensive congestive heart failure (CHF), acute and cardiocirculatory actions were determined by cardiac catheterization and forearm plethysmography, and ambulatory effects were assessed by echocardiography, nuclear angiography, treadmill exercise, and clinical symptomatology in 10 severe CHF patients. Captopril (90 mg) produced marked (peak 1 hour) and sustained (5 hours) left ventricular filling pressure (23 to 15 mm Hg), systemic vascular resistance decreases, and cardiac index increase (1.99 to 2.41 L/min/m2), while mean blood pressure declined mildly (87 to 80 mm Hg) without heart rate change. Both forearm venous tone and vascular resistance decreased considerably. After 1 week of ambulatory therapy (90 mg three times daily), nuclear angiographic ejection and echocardiogram shortening fractions increased, and exercise duration (341 to 453 sec) and New York Heart Association functional class (3.6 to 2.2) improved. Thus ACE-induced vasodilation by oral captopril improved cardiac performance and clinical status in refractory CHF. PMID- 6257101 TI - An immunocytochemist's view of gonadotropin storage in the adult male rat: cytochemical and morphological heterogeneity in serially sectioned gonadotropes. AB - This study was designed to elucidate hormone storage patterns in gonadotropes with the use of ultrastructural immunocytochemistry on serial ultrathin sections. Sets of six serial sections were strained for beta chains of LH, FSH, or the C Terminal sequence of ACTH, and 430 cells cut in triple or double serial section were collected from a group of seven normal adult male rats. Approximately 50- 80% of the cells contained both LH and FSH, and most of these were Type I cells which are distinguished by their round shape and heterogeneous populations of secretion granules. Cells containing only FSH or LH constituted, on average, 19% of the population. These were a mixed group, morphologically, and included Type II cells distinguished by their angular shape and population of secretion granules, 250 nm in average diameter. Also among the FSH cells (and a few LH cells in two of the rats) were Type III cells, which resemble the corticotrope. On average, 10% of the serially sectioned cells contained only ACTH. Our findings show the presence of subpopulations of gonadotropes containing only one of the hormones, in numbers large enough to support the hypothesis that they may be partly responsible for the nonparallel release of gonadotropins. Also, the FSH-LH cells seemed to vary in their staining intensity for the two hormones, suggesting that the gondaotropes are a fluid, heterogeneous population of cells capable of storing both or only one of the hormones. PMID- 6257102 TI - Immunocytological study on the differentiation of chick and quail adenohypophysis epithelial rudiments, grafted or cultivated in vitro: evidence for polypeptidic hormones. AB - Epithelial rudiments of adenohypohysis were removed from chick and quail embryos between days 3 and 5 of development. Chick rudiments were grafted for 11--13 days onto the chorioallantoic membrane of decapitated chick embryo hosts. Quail rudiments were cultivated in vitro for 6 days. Both grafted and cultivated Rathke's pouches differentiated into adenohypophyseal tissue. The adenohypophyseal tissue cultured on chorio-allantoic membrane exhibited cells reacting with the following immune sera: anti-beta-(1--24)ACTH, anti-alpha-(17- 39)-ACTH, anti-alpha-endorphin, anti-beta-endorphin and anti-beta-LPH, which also gave a positive reaction when applied to adenohypophysis of corresponding age which had differentiated in situ. In situ, corticotrophs were located exclusively in the cephalic lobe of adenohypophysis. Therefore, the differentiation of corticotrophs in the whole graft, i.e., from both cephalic and caudal lobes of Rathke's pouch, showed that the cells of the caudal lobe, or at least some of them, were uncommitted when the rudiment was removed. In vitro, tissue derived from Rathke's pouch contained cells reacting with antibodies to beta-(1--24) ACTH, alpha-(17--39)-ACTH, and beta-LPH, as did adenohypophysis from quail embryos of corresponding age (9--10 days), differentiated in situ. The differentiation of quail Rathke's pouch in vitro corroborates that differentiation can occur without influence from hypothalamus and, moreover, shows that at least some kinds of cells can differentiate without influence exerted by any other encephalic factors, and in the absence of mesenchyme. The question arises whether fibroblastic cells derived from Rathke's pouch cells act as feeder-cells and/or secrete some factors promoting differentiation. PMID- 6257103 TI - Immunocytochemical demonstration of anterior pituitary hormones in the pars tuberalis of long-term hypophysectomized rats. AB - The hormone-containing cells of the pars tuberalis of the rat adenohypophysis were studied, 4--5 months after hypophysectomy, with a double bridge immunocytochemical technique and with antisera directed against the hormones of the pars distalis. Corticotropes, lactotropes, somatotropes, thyrotropes, and gonadotropes were found in the pars tuberalis of all animals. These cells are well well situated to receive blood, nerve terminals, and tanycyte processes from the median eminence and, thus, to be influenced by the chemical messengers from the hypothalamus. It is concluded that the pars tuberalis has to be regarded as a potential source of adenohypophyseal hormones in an animal model traditionally considered to be free of such hormones. PMID- 6257104 TI - Immunoreactive adrenocorticotropin in rat brain: a neuroanatomical study using antiserum generated against synthetic ACTH. AB - In this study an antiserum generated against synthetic ACTH1--39 is used to provide a neuroanatomical map of ACTH-immunoreactivity in rat brain. Groups of ACTH-immunoreactive cell bodies were located in the basal hypothalamus, extending from the retrochiasmatic region to the mammillary nuclei. The fiber distribution indicates a broad innervation of structures in the hypothalamus, which include the medial preoptic region; bed nucleus of the anterior commissure and stria terminalis; perifornical region; periventricular stratum; and paraventricular, dorsomedial, arcuate, and mammillary nuclei. Fibers from the hypothalamus reach the amygdaloid nuclei directly in two separate bundles. A large dorsal ACTH immunoreactive bundle emerges from the anterior hypothalamic region, distributes to the periventricular thalamic nuclei, and continues more posteriorly to the midbrain periaquaductal gray. It is speculated that the cell bodies in the ventral tuberal region of the hypothalamus are responsible for the vast innervation of fibers to the forebrain, diencephalon, and brainstem. PMID- 6257105 TI - Transient protein-losing enteropathy and enlarged gastric rugae in childhood. AB - Data on two patients with massive but transient protein-losing enteropathy due to gastric disease suggest that antibody-mediated allergic reactions may have been responsible for the clinical picture. The majority of patients described in the literature have had evidence of a preceding or concomitant viral infection, and three of these have had evidence of infection with cytomegalovirus. Recovery occurred relatively rapidly in all patients without sequelae. The syndrome may be a variant of eosinophilic gastroenteritis. PMID- 6257106 TI - Cytomegalovirus in the perinatal period. PMID- 6257107 TI - Endogenous hyperinsulinism. AB - Endogenous insulin excess as a cause of hypoglycemia was described soon after the epic discovery of insulin in 1921. Rosco Graham removed an insulinoma and cured a patient's hypoglycemia in 1929. Adenomatosis of the islet cells as a cause of hypoglycemia was described in 1944 by Frantz, who advocated subtotal pancreatectomy for this disorder. Whipple's triad of 1. symptoms precipitated by fasting with 2. associated blood sugars of 50 mg.% or less and 3. relief of symptoms by glucose administration, is the classic description of the symptom complex of hyperinsulinism. Currently the opportunity for accurate diagnosis of hyperinsulinism has been enhanced by the availability of serum insulin radioimmunoassay (IRI). Nonetheless, delay in diagnosis with potentially tragic consequences is still common and this prompted a review of the clinical material at St. Luke's Hospital. Nine cases of organic hyperinsulinism were diagnosed between 1965 abd 1979 and form the basis of this report. PMID- 6257108 TI - Pneumonia: an eleven-year study in a pediatric practice. AB - Data from an 11-year study of acute lower respiratory tract illness were analyzed to provide added insight into the causes and patterns of occurrence of pneumonia in an outpatient pediatric population. Over 80% of all episodes of pneumonia occurred in children less than seven years of age; the peak attack rate was observed in 2-4-year-old children. A virus or Mycoplasma pneumoniae was isolated from 24% of children with pneumonia; 57% of all episodes occurred during outbreaks for which a viral or mycoplasmal cause could usually be identified. Respiratory syncytial virus (RSV), parainfluenza viruses types 1 and 3, adenoviruses, influenza A viruses and M. pneumoniae accounted for 86% of all isolates. Attack rates of pneumonia in preschool children were highest during periods of RSV and influenza A virus prevalence; M. pneumoniae was the most frequent isolate from school aged children. The data contained in this report augment the understanding of the causes of pneumonia in children and provide a data base for scientists interested in the prevention of lower respiratory tract illness in children. PMID- 6257109 TI - Epstein-Barr virus infections in a nursery. AB - Tests for Epstein-Barr virus (EBV) capsid antibody were carried out on 115 children, aged 4-32 months, on admission to and discharge from the Junior Village nursery, Washington, D.C. Forty-three children positive on admission remained positive at discharge, 44/72 negative on admission remained negative at discharge, and 28/72 negative on admission converted to positive at discharge. Age, sex and season did not appear to influence the rate of EBV seroconversion among the nursery children. The only identifiable factor that significantly increased the rate of EBV seroconversion was the duration of nursery residency. The rates were 1/9 (11%), 1/29 (3%), and 11/16 (69%) among children residing for 1.5-2.4, 2.5-4.4 and 4.5-7.4 months, respectively. Children residing in the nursery for 1.5-4.4 months and children residing at home had similar EBV seroconversion rates. For children residing in the nursery for 4.5-7.4 months, however, the observed EBV-seroconversion rate was much higher than the rate estimated for children living at home. PMID- 6257110 TI - Epidemic keratoconjunctivitis caused by adenovirus type 8: epidemiologic and laboratory aspects of a large outbreak. AB - During late 1977 and early 1978, 192 cases of epidemic keratoconjunctivitis occurred in a community in central Georgia. In 86 of these cases, the patient had been exposed to a single ophthalmologist's office (physician A) 3-22 days before onset of illness. Patients considered as cases were more likely to have had invasive ophthalmologic procedures than non-cases (p < 0.001), and a linear relationship existed between the number of procedures performed and the attack rate (r = 0.91, p < 0.05). Adenovirus type 8 (AV8) was identified as the responsible pathogen by culture and/or antibody determination for 20 of these patients. Group-specific AV hexon antigen and type specific dodecon antigen were identified in four of seven ophthalmic solutions obtained from physician A's office. The outbreak stopped after proper control techniques were initiated. PMID- 6257111 TI - Viral diabetes mellitus in man and experimental animals. AB - Accumulating evidence strongly suggests that viruses may play an etiologic role in some cases of diabetes mellitus. The importance of environmental factors in the pathogenesis of the disease is suggested by genetic and epidemiological observations. Group B Coxsackie viruses and mumps virus have been implicated, and the evidence suggests that several other agents also could play a role in the disease. In experimental animals, a picornavirus similar to the Coxsackie viruses exhibits specific tropism for the beta cells of the islets of Langerhans, causing a disease in mice that is similar to juvenile-onset diabetes. In these animals, genetic and metabolic factors appear to influence the severity of beta cell injury. Immunopathologic considerations also may be important. In man, histocompatibility genes are important determinants of juvenile-onset diabetes and abberations of immune responsiveness to beta cells have been demonstrated. In experimental animals, cell-mediated immunity develops subsequent to the occurrence of viral-induced lesions in the islets. Viewed in concert, the evidence supports the notion that certain "wild" viruses may possess specific tropism for beta cells and destroy them during the course of a systemic infection. Host factors clearly play a role, but their relative importance in the pathogenesis of the disease remains to be defined. PMID- 6257112 TI - Value of serial measurement of serum angiotensin converting enzyme in the management of sarcoidosis. AB - Serial serum samples from 35 patients with histologically proved sarcoidosis were measured for angiotensin converting enzyme activity. The serum angiotensin converting enzyme (SACE) activity was compared with the clinical activity of sarcoidosis. In both the treated and untreated group, the SACE activity closely paralleled the clinical status. There was agreement between SACE index and clinical index in 81 of 101 paired observations. It appears that SACE activity is a good reflection of granulomatous activity in sarcoidosis. Once the decision has been made to treat sarcoidosis, serial SACE determinations are helpful in monitoring the dose and duration of therapy with corticosteroids. PMID- 6257113 TI - Mechanism of luteolysis: effect of estradiol and prostaglandin F2 alpha on corpus luteum luteinizing hormone/human chorionic gonadotropin receptors and cyclic nucleotides in the rhesus monkey. AB - Recent studies from our laboratory suggest that estrogen-induced luteolysis in the primate may be mediated through synthesis of prostaglandin F2 alpha (PGF2 alpha). To elucidate further the mechanism of luteolysis, normally cycling rhesus monkeys received intra-corpus luteum (CL) injections of estradiol (100 microgram), PGF2 alpha (500 microgram), or the appropriate vehicles on the seventh day after the preovulatory estradiol surge. Peripheral vein blood was drawn, at 30-minute intervals for 6 hours for progesterone and luteinizing hormone (LH) assays. Five hours after intra-CL injection, the CL was excised and the LH/human chorionic gonadotropin (hCG) receptor-binding activity and cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) were measured. PGF2 alpha significantly (p < 0.05) lowered progesterone within 1 hour, while the time required for estradiol to lower progesterone significantly was 3.5 hours; there was no significant change in LH, Estradiol and PGF2 alpha significantly (p < 0.05) decreased the LH receptor-binding capacity at 5 hours, without any change in the binding affinity. Also PGF2 alpha significantly (p < 0.05) increased cGMP in the CL, while cAMP remained unchanged; estradiol treatment resulted in a significant (p < 0.05) increase in cAMP with no change in cGMP. This study suggests that estradiol and PGF alpha cause a decrease in progesterone secretion by a loss of the LH/hCG receptor and the PGF2 alpha may act further through the cGMP system. PMID- 6257114 TI - Activation of fast skeletal muscle: contributions of studies on skinned fibers. AB - The membrane potential of vertebrate twitch fibers closely controls Ca fluxes between intracellular compartments, which in turn control contraction. Recent work on intracellular Ca movement is reviewed in the general context of current efforts to synthesize physiological, biochemical, and structural observations on the contractile mechanism and its regulation, emphasizing the increasing role of functionally skinned fibers in this synthesis. Skinned fiber preparations, with removed or disrupted sarcolemma, bridge the gap between properties of isolated subsystems and their constrained operation in the intact fiber. Recent studies indicate that the surface action potential propagates along the transverse tubules, but not the sarcoplasmic reticulum (SR), which appears to be a distinct intracellular compartment. Voltage-dependent charge movements in the transverse tubules probably control Ca flux across the SR membranes. Current questions concern the mechanism of the signal that bridges the junctional gap between the two membrane systems, the mechanism and properties of the activated Ca efflux to the myofilament space, and the operation of the Ca pump of the SR during activation. New methods applied to intact fibers, cut fibers, skinned fibers, and subcellular systems are yielding the kind of information needed for a complete description of these central steps in excitation-contraction coupling and of Ca regulation of the myofilaments. PMID- 6257115 TI - An electrogenic component of resting potential in rabbit ventricular muscle? AB - The resting potential and the intracellular Na and K concentrations (Nai, Ki) were determined at several extracellular K concentrations (Ko) between 0.5 and 18 mM and after inhibition of the sodium pump with 0.5 microM ouabain. Exposure to low Ko (0.5 mM) produced a transient hyperpolarization (from -80 to -100 mV) followed by a depolarization that led to a stable potential of -60 mV within 25 min. Similar potential levels were observed in the presence of ouabain regardless of the Ko/Ki ratio. Intracellular sodium increased at Ko < 5 mM, whereas Ki rose at Ko less than or equal to 1.0 mM. Because of the large decrease of Ki at Ko = 0.5 mM, Ko/Ki was the same at 0.5 and 1 mM. However, the resting potentials at the steady state differed by 50 mV at these concentrations. A PNa/PK of 0.032 for the control conditions was obtained with the Mullins-Noda equation using 2.5 as the Na-K coupling ratio. This PNa/PK value yielded a Goldman potential of -69 mV; so we estimated that electrogenic sodium extrusion contributed -10 mV to the resting potential. The size of the electrogenic potential increased as Ko was lowered from 5 to 1 mM. This finding suggests that the control of the Na-K coupling ratio may be independent of the mechanism that controls the pumping rate. PMID- 6257116 TI - Dependence of membrane potential on extracellular ionic concentrations in myotonic goats and rats. AB - Intracellular potassium concentration([K]i) and the resting sodium-to-potassium permeability ratio (alpha = PNa/PK) were determined by recording resting potentials at 25 degrees C in six solutions with variable potassium concentrations, constant [K+] + [Na+], and constant [K+] X [Cl-] product and fitting the results by nonlinear least squares to the Goldman-Hodgkin-Katz equation. Fits to models including chloride permeability terms suggest that chloride is in Donnan equilibrium in the muscles studied. External intercostal muscle was biopsied from anesthetized normal goats and goats with hereditary myotonia. In normal goat muscle, alpha was 0.012 +/- 0.001 (mean +/- SE, n = 11), and [K]i was 133 +/- 6 mM (n = 9); myotonic goat muscle did not differ from this. Extensor digitorum longus (EDL) muscle was removed from anesthetized male Wistar rats and from like rats pretreated with a single large dose of 20,25 diazacholesterol (DAC). In normal rat EDL, alpha was 0.019 +/- 0.002 (n = 12), and [K]i was 142 +/- 4 mM (n = 12). In the 16-day DAC-treated rats, alpha was significantly reduced (P < 0.002) to 0.010 +/- 0.002 (n = 8), and [K]i was slightly reduced by DAC. It is concluded that DAC reduced PNa in rat fibers. Tetrodotoxin at 5 microM did not affect either parameter in the rats. PMID- 6257117 TI - Calcium affects insulin release and membrane potential in islet beta-cells. AB - Insulin release from perfused rat pancreas was compared with membrane potentials of single beta-cells from perifused mouse islets during glucose stimulation (11.1 mM) in the presence of varying Ca and Mg concentrations. Depolarization was associated with insulin release and hyperpolarization with its suppression, irrespective of Ca concentration. After sudden reduction of Ca and Mg (to 0.05 and 0.01 mM, respectively), glucose-stimulated insulin release was maintained while the cell membrane depolarized, leading to a reversed pattern of burst activity. Readdition of Ca and Mg caused suppression of insulin release that paralleled hyperpolarization of the cell membrane. This suppression was transient, lasting < 5 min, and was due mainly to readdition of Ca. Patterns of insulin release during reduction of Ca and Mg in the presence of valinomycin (1 microM), diphenylhydantoin (25 microgram/ml), and ethyleneglycol-bis(beta aminoethylether)-N,N'-tetraacetic acid (0.037 and 1.0 mM) were also studied. In conclusion, the relative concentrations of Ca and Mg and the membrane potential per se are important in the release of insulin. Also, under certain experimental conditions, Ca can block glucose-stimulated insulin release, possibly by increasing K+ permeability. PMID- 6257118 TI - Membrane permeability to the molecular and ionic forms of DMO in barnacle muscle. AB - The time course of the intracellular pH (pHi) of barnacle muscle fibers was followed using microelectrodes while the fibers were exposed to 15 mM of the weak acid 5,5-dimethyloxazolidine-2,4-dione (DMO) at pH 6.5. The rapid initial fall in pHi was used to determine the membrane permeability to the DMO molecule, while the much slower fall during the subsequent plateau phase yielded the permeability to the DMO ion. This experimental approach and the mathematical treatment of the data can be used to obtain the membrane permeabilities to other weak acids or bases. We found values of 1.9 X 10(-4) cm/s for the permeability to the DMO molecule and 1.5 X 10(-7) cm/s for the permeability to the ion, assuming the fiber to be a cylinder. Thus the permeability of the neutral form is about 10(3) times that of the ionized form. At commonly encountered conditions of pHi = 7.3, outside pH = 7.5, and membrane potential = -52 mV, this permeability ratio introduces an error of only -0.01 to -0.02 into the determination of pHi based on the distribution of DMO. PMID- 6257119 TI - pH regulation in barnacle muscle fibers: dependence on extracellular sodium and bicarbonate. AB - Intracellular pH (pHi) regulation was studied in barnacle muscle fibers with pH sensitive microelectrodes. The cells were acid loaded, and the subsequent recovery of pHi was monitored. The rate of recovery was reduced by one-third when external Na+ ([Na+]o) was replaced by Li+, but recovery was completely abolished when Na+ was replaced by choline or N-methyl-D-glucamine. In other experiments, varying amounts of Na+ were replaced by choline, and the acid extrusion rate, derived from the recovery rate of pHi, was calculated at a single value of pHi, 6.80. The dependence of the acid extrusion rate on [Na+]o could be described by Michaelis-Menten kinetics; at pHo (extracellular) = 8.0 and [HCO3-]o (extracellular) = 10 mM, the apparent Km and Vmax were 59 mM and 1.3 mmol x l(-1) x min-1. When [HCO3-]o was reduced to 2.5 mM at the same pHo, Km did not change significantly, but Vmax was substantially reduced. On the other hand, when pHo was reduced to 7.4 at constant [HCO3-]o, Vmax changed only slightly, but Km increased substantially. In similar experiments, we examined the dependence of the acid extrusion rate on [HCO3-]o. At pHo = 8.0 and [Na+]o = 440 mM, the apparent Km and Vmax were 4.1 mM and 2.1 mmol x 1-1 x min-1. When pHo was reduced to 7.4, Vmax was not altered, but Km substantially increased. The kinetic data are discussed in terms of the role of pHo, [Na+]o, and [HCO3-]o in the pHi regulating system. PMID- 6257120 TI - Neural influences on oscillations in basal plasma levels of insulin in monkeys. AB - The effects of cholinergic and adrenergic blocking agents on the period and amplitude of sustained oscillations in plasma levels of insulin and glucose were studied in 16 overnight-fasted conscious rhesus monkeys. Blood samples were withdrawn at 2-min intervals before and during or following administration of drugs that affect neurotransmission. Cholinergic blockade with atropine had no effect on the oscillations. alpha-Adrenergic blockade with phentolamine caused a rise in plasma insulin that lasted less than 10 min and was followed by a slight, although not consistent, decrease in mean insulin and a consistent small decrease in glucose. There was a sustained increase in heart rate, but no effect on the oscillations of insulin or glucose. beta-Adrenergic blockade induced by propranolol led to persistent decreases in mean plasma insulin 60% below the base line, small but variable decreases in glucose, and a sustained decrease in heart rate, but no change in period or relative amplitude of the oscillations in plasma levels of either insulin or glucose. General anesthesia with pentobarbital did not eliminate these oscillations. Our observations on the failure of the blockade of certain putative efferent pathways or depression of higher cortical centers to alter the period of the oscillations of insulin reduce the likelihood that the oscillations are transmitted from a pacemaker in the central nervous system. PMID- 6257121 TI - Identifying secondary active solute transport in epithelia. AB - This Editorial Review analyzes the adequacy of the strategies that are commonly used to establish whether the active transport of a solute does or does not occur by secondary active transport. First, the energetics of noncoupled (passive) diffusion, primary active transport, secondary active transport (coupled diffusion), and solvent drag are briefly described. Second, the kinetics of noncoupled and coupled diffusion processes are discussed. Third, the special difficulties of identifying secondary active solute transport in epithelia are outline. Several factors are described that may obscure or mimic true coupled diffusion. Last, the use of transport inhibitors for identifying coupled diffusion processes is briefly illustrated. The adequacy of the strategies that have been employed to evaluate the role of luminal membrane Na+-H+ exchange in mediating proximal tubular acidification is particularly emphasized. It is concluded that many of the findings apparently supporting a major contribution of Na+-independent, primary active H+ secretion to the proximal tubular acidification process are not necessarily inconsistent with secondary active H+ secretion via Na+-H+ exchange. PMID- 6257122 TI - Comparison of the "mammal machine" and the "reptile machine": energy production. AB - Standard metabolism and body composition were measured in Amphibolurus nuchalis and Mus musculus (a reptile and mammal with the same weight and body temperature). The metabolic capacity for energy production was assessed in liver, heart, brain, and kidney in the lizard and mouse by two methods: measurement of mitochondrial enzyme activity (cytochrome oxidase) and measurement of both mitochondrial volume density and membrane surface area. Both methods gave a three to sixfold greater capacity for energy production in the mammal compared to the lizard which is less than the eightfold difference in their standard metabolisms. The difference in energy production capacity was not due to any single parameter but was a summation of several smaller differences. The mammal had relatively larger internal organs than the reptile, their organs had a greater proportion of mitochondria, and their mitochondria had a greater relative membrane surface area. These differences, it is suggested, may be due in part to different thyroid function in reptiles and mammals. PMID- 6257123 TI - Pharmacologic responsiveness of isolated single eccrine sweat glands. AB - Pharmacologic responsiveness of the eccrine sweat gland has never been studied under well-defined in vitro experimental conditions. Using isolated cannulated single monkey palm eccrine sweat glands, the dose response to both cholinergic and alpha- and beta-adrenergic agents and the effects of various antagonists on agonists were studied. The maximal sweat rate was highest after stimulation with cholinergic agonists, was lower with the beta-adrenergic agonist, and was least with the alpha-adrenergic agonist. Each secretory response was inhibited by its specific antagonist. Attempts to demonstrate the spare receptor, if any, by means of preincubation of the glands with N-(2-chlorethyl)dibenzylamine (Dibenamine) were unsuccessful. From the hyperbolic dose-response curves the values for KA and KB, dissociation constants for agonists and antagonists, respectively, were thus tentatively estimated according to Clark's classical receptor theory. Schild plots for each agonist-antagonist interaction produced straight lines with slopes of near unity, indicating the adequacy of the methodology. It was concluded that the isolated eccrine sweat glands retain their pharmacologic viability in vitro and show responsiveness to cholinergic as well as both alpha- and beta-adrenergic stimulations. PMID- 6257124 TI - Effects of amino acids on chloride transport in Aplysia intestine. AB - This investigation was principally undertaken to examine the mechanism by which organic solutes (amino acids) stimulate chloride transport across the Aplysia californica intestine. Isolated intestine, mounted between identical oxygenated seawater solutions, maintained stable transmural potential differences (serosa negative) and short-circuit currents for several hours at 25 degrees C. The addition of glycine to the mucosal solution stimulated rapid sustained increases in these electrical characteristics. The change in short-circuit increased curvilinearly with increasing concentrations of mucosal glycine. Mucosal glycine stimulated transmural potential difference and short-circuit current after mucosal phlorizin had partially inhibited D-glucose stimulation of the electrical characteristics. Mucosal glycine enhanced the transmural electrical characteristics. Mucosal glycine enhanced the transmural electrical characteristics after serosal ouabain had abolished them. The major portion of the amino acid-induced short-circuit current was carried by a net, active, chloride transfer from mucosa to serosa as determined by flux measurements. These results suggest that the amino acid-induced effect on chloride transport is mediated by a common mucosal membrane carrier for both sodium and the amino acid. PMID- 6257125 TI - Behavioral and biological effects of acute beta-endorphin injection in schizophrenic and depressed patients. AB - In this double-blind study, beta-endorphin, 4-15 mg, was administered intravenously to 6 schizophrenic and 4 depressed patients. There were neither significant differences in behavioral ratings between beta-endorphin and placebo for the overall group nor for either the schizophrenic or depressed subgroup. Clinical worsening and improvement were observed in individual schizophrenic patients. There was no evidence of late-appearing therapeutic effects in 4 schizophrenic patients rated for 5 consecutive days after placebo and drug infusions. In 1 patient 10 mg of beta-endorphin produced neuroendocrine effects comparable to those produced by 5 mg of intravenously administered methadone; in 2 other patients it produced large increases in circulating opioid activity as determined by radioreceptor assay. These biological data support the notion that parenterally administered beta-endorphin exerts significant opiate-like activity in vivo. PMID- 6257126 TI - Environmental contamination of human breast milk. PMID- 6257127 TI - Pattern of immunoreactive glucagon in portal, arterial and peripheral plasma before and after removal of glucagonoma. AB - Gel fractionation of portal, arterial and peripheral plasma glucagon levels was performed before and after the successful removal of a glucagonoma. A 47 year old woman had symptoms of dermatitis, weight loss, anemia and diabetes mellitus over a 16 year period. Removal of the alpha-cell tumor corrected all of her symptoms. Gel filtration of portal, arterial and peripheral blood showed two peaks of glucagon radioimmunoassay activity, a higher molecular weight glucagon with a molecular weight of 9,000 and a 3,500 dalton glucagon. Five minutes after tumor removal, the higher molecular weight glucagon had disappeared completely from the arterial and peripheral blood but not from the portal vein. PMID- 6257128 TI - Resection of primary solid hepatic tumors. AB - Experience with surgical management of 60 solid hepatic tumors was analyzed with respect to the size and type of lesion, extent of resection, operative risk, postoperative complications and survival after resection. The present study concerns 46 primary hepatic malignancies and 14 benign lesions. Lesions varied in size from 5 to 29 cm (average 13). The extent of resection required for removal was related to both the size and location of lesions. Twelve trisegmentectomies, 33 hemihepatectomies and 15 major segmentectomies were done. There were three postoperative hospital deaths, two of which were related to extensions of tumor that precluded safe resection. Postoperative complications necessitated hospital convalescence for more than 21 days in 9 of the 57 surviving patients; the hospital stay of the remaining patients averaged 12 days. The 10, 5 and 3 year survival rates of patients who had resection of malignant lesions were 33, 36 and 65 percent, respectively. We conclude that aggressive treatment of primary hepatic malignancy is justified by acceptable operative risk and significant palliation or improved survival. PMID- 6257129 TI - Pancreatic islet transplantation in dogs. Critical factors in technique. AB - Total pancreatectomy and intrasplenic autotransplantation of islet tissue was carried out in dogs. The resected pancreas was prepared by the partial islet isolation technique of gland distention, mincing and collagenase digestion. The influence of variations in technique was studied. Using otherwise identical methods, five collagenase lots were compared. Three lots were effective, resulting in successful transplants in 23 of 26 dogs. Two ineffective lots produced no successes in six dogs (p < 0.001). When minced particle size was varied, particles which would pass freely through a 16 gauge needle resulted in no successes in six dogs. With a larger particle size that would pass freely only through a 15 gauge needle, 15 of 15 transplants were successful (p < 0.001). When tissue was minced by hand, 8 of 11 transplants were successful, compared with 15 of 15 when mechanical mincing was used. With variation in collagenase concentration, success occurred in four of six using 300 units of collagenase/ml of minced tissue, in four of six using 600 units and three of six using 1,200 units. It is concluded that minced particle size and collagenase lot are critical variables in this technique of islet transplantation. Mincing method and concentration of collagenase do not appear to be important variables. PMID- 6257130 TI - Improving survival in adenocarcinoma of the duodenum. AB - The records of 104 patients with primary adenocarcinoma of the duodenum were reviewed. All patients were followed up to the date of this report, 91 for at least 5 years. Melena was an ominous preoperative finding. Survival was directly related to nodal status, the grade of the lesion, and the ability of the surgeon to minimize or eliminate operative mortality. Fifty percent of the lesions were resectable for cure, and the 5 year survival rate for patients with resectable lesions was 46 percent. All eight patients treated with segmental resections for lesions in the third and fourth portions of the duodenum survived at least 5 years. These data are a great improvement over those in previous reports and suggest that this disease may be much more treatable than previously believed. PMID- 6257131 TI - [Effect of the cesarean section operation on the adaptation of newborn infants]. PMID- 6257132 TI - [Plasma levels of cAMP and cGMP in chronic urticaria]. PMID- 6257133 TI - Scanning electron microscopy of frozen-cracked, dry-cracked and enzyme-digested tissue of human malignant choroidal melanomas. AB - By applying cracking and enzyme-digestion methods to tissue of human malignant choroidal melanomas, SEM was used to visualize the interior of the cells, their membranes, nuclei and organelles. Single cells were depicted to their full extent. Apart from a three-dimensional impression of the structures and their surfaces, the methods also made it much easier to measure cells and cell components than by conventional methods. PMID- 6257134 TI - Recovery from pancuronium. A comparison between old and young patients. AB - The rate at which paralysis from pancuronium could be reversed by neostigmine was monitored in two groups of patients, one elderly and the other young adults. Some patients were found to have prolonged recovery times, and this slow reversal occurred more frequently in the older group of patients. Possible reasons for this are discussed. PMID- 6257135 TI - Performance of nonrigid ion-exchange packings of small particle size in the separation of cytochrome c and derivatives by high-pressure liquid chromatography. PMID- 6257136 TI - Simple radioassay for uridine phosphorylase and 5'-nucleotidase. PMID- 6257138 TI - A simple electrophoresis system for multiple agarose slab gels. PMID- 6257137 TI - An adaptation of the sodium periodate/sodium borotritide labeling procedure which allows the unambiguous identification of synaptic sialoglycoproteins. PMID- 6257139 TI - Concanavalin A--Sepharose purification of soluble Na,K-ATPase from rectal glands of the spiny dogfish. PMID- 6257140 TI - A handy assay for collagenase using reconstituted fluorescein-labeled collagen fibrils. PMID- 6257141 TI - Chemical synthesis of [32P]pyrophosphate with high specific activity. PMID- 6257142 TI - An easy, quantitative method for detection of endonuclease activity. PMID- 6257143 TI - A simple qualitative method for the detection of nucleases. PMID- 6257144 TI - Continuous colorimetric monitoring of the fructose bisphosphate aldolase reaction. PMID- 6257145 TI - New method for determining the extent of proline hydroxylation by measuring changes in the ratio of [4-3H]:[14C]proline in collagenase digests. PMID- 6257146 TI - Quantitative isolation of radiolabeled metabolites without chromatography: measurements of the biosynthesis of purines, pyrimidines, and urea in isolated hepatocytes. PMID- 6257147 TI - Lung development and the pulmonary surfactant system: hormonal ifluences. AB - The effect of hormones on developmental events is not a new area of scientific investigation. However, in the last decade, the developing lung has been the focus of an increasing amount of basic and applied research. Inadequate development of the newborn's respiratory system precludes extra-uterine existence; indeed, such respiratory inadequacy has been a leading cause of death in premature infants. Tremendous strides have been made in understanding the basic cell biology of the developing lung. Much has been learned about the source, composition, and function of pulmonary surfactant, a surface-active material produced by the lung and essential to alveolar stability. Deficient stores of this material is a major etiologic factor in the respiratory distress syndrome of the newborn (RDS). This fact, coupled with observations that certain hormones can accelerate lung development and the consequent availability of adequate stores of pulmonary surfactant, has led to a large body of literaturae dealing with the effects of hormones (and other agents) on lung development. It is the purpose of this literature review (1) to discuss the various kinds of investigations which have linked surfactant synthesis to the type II pulmonary epithelial cell; and (2) to review the current status of research dealing with the effects of glucocorticoids and thyroid hormones on lung maturation. PMID- 6257148 TI - The relationship between receptor occlusion and the frequency sweep electromyogram during competitive neuromuscular blockade. AB - The purpose of this study was to correlate the frequency sweep electromyogram (FS EMG) responses to various levels of receptor occlusion during partial neuromuscular blockade by d-tubocurarine (dTC). The FS-EMG represents the integrated compound muscle action potential induced by intra-muscular electrical stimulation as the stimulus frequency increases exponentially from 1 to 100 Hz. The FS-EMG response was recorded from the tibialis anterior muscles of six adult cats at different levels of neuromuscular blockade during recovery from intravenously injected dTc, 0.25 mg/kg. The fraction of receptors blocked was estimated by measuring the depolarization produced by proximate intraarterial injection of graded doses of succinylcholine. The FS-EMG became diminished for driving frequencies greater than 50 Hz when receptor occupancy was about 25-30 per cent. The responses corresponding to lower stimulus rates declined only at increasing levels of occlusion. The FS-EMG response to low-frequency stimulation did not diminish until 70 per cent of the available receptor pool was blocked. Simultaneous measurement of muscle force demonstrated a depressed response equivalent to that of the FS-EMG. These data were compared with the sensitivities reported for other tests of neuromuscular block. The frequency sweep electromyogram appears to be about as sensitive as determination of responses to sustained 5-second tetanic stimulation at 200 Hz, but more sensitive than determination of responses to tetanic stimulation at 100 Hz or twitch responses, or train-of-four measurements. PMID- 6257149 TI - Assessment of neuromuscular function in infants. AB - This study was conducted to measure neuromuscular transmission in newborn infants. Age-dependent differences in neuromuscular transmission and the effect of nitrous oxide anesthesia upon neuromuscular function were assessed in pediatric surgical patients following induction of anesthesia with methohexital by the use of the frequency sweep electromyogram (FS-EMG). Children older than 12 weeks' chronologic age usually had FS-EMG responses similar to those of adults, whereas infants less than 12 weeks old had significantly less pronounced FS-EMG responses at high stimulation frequencies (>50 Hz). Administration of 70 per cent nitrous oxide induced 11-38 per cent reductions in the amplitudes of the FS-EMG responses at all frequencies of stimulation in the younger group. A positive correlation was found between inability to sustain a tetanic contracture (FS-EMG fade) in the 50-100-Hz region of stimulation and percentage depression of the FS EMG response induced by nitrous oxide. PMID- 6257150 TI - [Intercarotid chemodectoma. Anatomo-surgical considerations]. PMID- 6257151 TI - Correlation of IgG and IgE antibody levels to honey bee venom allergens with protection to sting challenge. AB - A group of 25 honey bee venom allergic patients were treated with commercial honey bee venom at a monthly maintenance dose of 100 micrograms for approximately one year. At the end of one year 24 patients were intentionally challenged and one was accidentally challenged. Three patients experienced significant systemic reactions to challenge and three experienced minor reactions. Sera obtained before commencing therapy, at maintenance and before challenge were tested by radioallergosorbent test (RAST), double antibody technique and protein A RAST for IgE and IgG antibody levels to all five known honey bee venom allergens. All of the treatment failures experienced at least a two-fold rise in IgG antibody against phospholipase. The ratios of IgG to IgE antibodies in the pre-challenge specimens were analyzed by a graphical method. Four patients had inadequate responses to at least three of the five allergens and three of these patients were those who experienced severe reactions to challenge. Sixteen patients had adequate responses to all five allergens, four patients to four allergens and one patient to three allergens; three of these patients experienced minor or local reactions to challenge and the remainder no reaction. No single allergen identified only the three severe reactors but three allergens identified all three reactors. The diagnostic efficiency of the criteria used for assessing protection was 0.96. The only non-correlating case was classifying a single nonreactor as at risk. No patients were misclassified as protected. PMID- 6257152 TI - [Trophoblastic gestational diseases. Triploid syndrome, perivillous trophoblastic hyperplasia, trophoblastic pseudotumor, trophoblastic microcarcinoma and carcinoma]. AB - Comparing the cytogenetic and morphological data on cases of hyperplasia and neoplasia of the trophoblast allows some conditions to be better defined and separated. The term partial mole or embryonic mole should be replaced by the term triploid syndrome because of the especially strong correlation between the triploid caryotype and the special aspect of the placenta. Triploidy is usually the result of fecundation of a haploid ovule by two spermatozoids, probably due to the similarity of the haploids of the two parents, as is suggested by the study of HLA antigens. Classical hydatidiform mole, or perivillous trophoblastic hyperplasia, is usually discovered earlier, during an ultrasound examination or abortion and its histological diagnosis is easy. The caryotype of complete hydatidiform mole is diploid, nearly always XX, with the two sex chromosomes coming from the father (the maternal sex chromosome being eliminated). The caryotype of vesicular dystrophia without trophoblastic hyperplasia is, on the other hand, normal. Trophoblastic microcarcinomas have a better known presentation. And trophoblastic carcinomas are distinct from non-trophoblastic neoplasms which secrete HCG and from benign trophoblastic pseudo-tumors which are often non-secretory. PMID- 6257153 TI - Pulmonary function loss in Vermont granite workers. A long-term follow-up and critical reappraisal. AB - Previous studies of Vermont granite workers averred that pulmonary function loss was occurring at 2 to 3 times the normal rate. The excess loss was attributed to the current, relatively low concentrations of dust prevailing in the stone sheds. Because the Vermont State Health Department had traditionally provided surveillance of granite workers to detect evidence of occupationally related illness, we offered pulmonary function screening to any currently employed worker. Spirometric data from the first 150 workers, compared with data from the previous studies, showed a large increase in the FVC and a smaller increase in the FEV1. We therefore undertook a survey of the entire stone shed work force, as well as of retired workers tested previously. The results in 487 current workers indicated an overall increase in FVC from 1974 to 1979 of 0.540 L, and an increase in FEV1 of 0.030 L: predicted losses based on the previous studies were 0.350 to 0.400 L in FVC and 0.250 to 0.350 L in the FEV1. Analysis of data in various subgroups, such as retired workers or those with more than 20 yr of work experience, also showed increases in FVC, and either slight gains or minimal losses in FEV1. The possible reasons for apparent improvement in pulmonary function are discussed. We concluded that technical deficiencies in the previous studies led to exaggerated and erroneous estimates of loss. At this time, the actual decrement in pulmonary function values for exposed granite workers is not known and requires further investigation. Because the newly proposed, stricter standard, for silica was importantly influenced by the previous studies, we believe that adoption of this standard would be premature. PMID- 6257154 TI - Altered oxidative metabolic responses in vitro of alveolar macrophages from asymptomatic cigarette smokers. AB - Superoxide anion (O2) release by alveolar macrophages (AM) from young asymptomatic cigarette smokers was greater than that by AM from age-matched nonsmokers. Greater O2 release by AM from cigarette smokers was observed before and after stimulation by bacteria or phorbol myristate acetate (PMA). In contrast, oxygen uptake and glucose (1(-14)C) oxidation by unstimulated or stimulated AM from cigarette smokers was the same as that by AM from non-smokers. The selective increase of O2 release by AM from cigarette smokers was not due to a lack of O2 scavenging agent within the cells, since intracellular superoxide dismutase (SOD) was increased in AM from smokers. The potential importance of enhanced O2 release by AM from cigarette smokers was confirmed by demonstrating that lysis of fibroblasts induced by AM from smokers was completely prevented by addition of SOD and catalase. PMID- 6257155 TI - Steady state kinetics of the (Ca2+ + Mg2+)-dependent P-nitrophenylphosphatase activity of sarcoplasmic reticulum vessicles. AB - The true substrate of the (Ca2+ + Mg2+)-dependent p-nitrophenylphosphatase activity of sarcoplasmic reticulum vesicles is the Mg. p-nitrophenylphosphate complex. The activity displays a hyperbolic dependence for the substrate (Km = 1.51 mM). The Ca2+ dependence is sigmoidal, with a K0.5 of 0.52 microM, which is the same as the observed for the ATPase activity determined in similar experimental conditions. However, the value of the Hill coefficient (3.0) is about twice as that observed for ATP hydrolysis. Simultaneous measurement of the hydrolysis of p-nitrophenylphosphate and ATP or acetylphosphate showed that all three substrates share a common catalytic site, while ATP is the only one of them which interacts also with a regulatory site, what explains the complex dependence of the ATPase activity on the substrate. Permeabilization of the vesicles to Ca2+, or the addition of K+ to the assay media, do not activate the hydrolysis of p-nitrophenilphosphate, contrarily to what is observed when ATP is the substrate. PMID- 6257156 TI - [Effects of sulfomethylation on the mechanism of action of colimycin towards "Escherichia coli" B (author's transl)]. AB - Colimycin is sulfomethylated in order to inactivate it temporarily in vivo. In vitro, this process may have unexpected results because the experiment is carried out within a closed system. The time required to activate the antibiotic varies according to incubation conditions. The freed sulfomethyl groups are probably eliminated in vivo. In vitro, these residues may interact with the outer membrane of Escherichia coli B which is charged with badly positioned molecules of colimycin, thus creating a barrier for the active molecules. As the expected mechanism of polymyxin B or E action include first electrostatic interactions, it is not surprising that a modification of the ionic balance of the medium should be of such importance. PMID- 6257157 TI - Sixth Daniel C. Baker, Jr. Memorial Lecture, Induction of cancer by DNA viruses. AB - The life cycles of the tumor virus SV40 and polyoma are discussed with particular emphasis on the role of the viral coded proteins which mediate the transformation of normal cells into their cancerous equivalents. One of more of these proteins possibly act by stimulating directly the synthesis of cellular DNA, while others may mimic the action of polypeptide mitogens that act at the cell surface. PMID- 6257158 TI - [Subcapsular renal hematoma. Report of two cases revealing benign cortical tumors (author's transl)]. PMID- 6257159 TI - Poliovirus retention in 75-cm soil cores after sewage and rainwater application. AB - The adsorption rate of a guanidine-resistant strain of poliovirus LSc 2ab was measured in Long Island soils with in situ field cores (10.1 by 75 cm). The test virus was chosen because it exhibited soil adsorption and elution characteristics of a number of non-polioviruses. After the inoculation of cores with seeded sewage effluent at a 1-cm/h infiltration rate, cores were extracted, fractionated, and analyzed for total plaque-forming units per each 5-cm fraction. The results showed that 77% of the viruses were adsorbed in the first 5 cm of soil. An additional 11% were found in the 5- to 10-cm fraction, and a total of 96% of the viruses were adsorbed by 25 cm. The remaining 4% were uniformly distributed over the next 50 cm of soil, with a minimum of 0.23% in each soil section. Few viruses (< 0.22%) were observed in core filtrates. Analysis of the viral distribution pattern in seeded cores, after an application of a single rinse of either sewage effluent or rainwater, indicated that large-scale viral mobilization was absent. However, localized areas of viral movement were noted in both of the rinsed cores, with the rainwater-rinsed cores exhibiting more expensive movement. All mobilized viruses were resorbed at lower core depths. PMID- 6257160 TI - New method for large-scale growth; and concentration of the Epstein-Barr viruses. AB - Efficacious systems are described for the large-scale growth in tissue culture and concentration of infectious (P3HR-1) and transforming (B95-8) Epstein-Barr virus. Also recorded here are our updated procedures for growing stock cultures and protocols to harvest fluids containing biologically active virus which is infectious or transforming. Various methods of concentrating biologically active Epstein-Barr virus have been evaluated. Cellular debris can be removed efficiently and rapidly from culture harvest fluids by clarification through a JCF-Z continuous-flow rotor. Efficient and reliable virus concentration was achieved by molecular filtration with Millipore Pellicon cassettes, using flow rates to 10 liters/h to produce fivefold concentrates followed by pelletization in a fixed-angle rotor. Data from recent production lots showed an average infectivity titer for P3HR-1 virus of 10(4.5) early antigen units per ml (100 fold concentrate) and 10(5.7) transforming units per ml (200-fold concentrate) for B95-9 virus lots. PMID- 6257161 TI - Effects of environmental variables and soil characteristics on virus survival in soil. AB - Because of the increasing emphasis placed upon land application as a means of wastewater disposal, it is important to evaluate the influences of different factors upon virus survival in soil. The objective of this study was to measure the effects of various environmental variables on virus persistence. Test samples of soil were placed in vials, and the soil was wetted with suspensions of virus in either distilled water, unchlorinated secondary sewage effluent, or mixtures of effluent and water. The viruses used were coxsackieviruses A9 and B3, echovirus 1, poliovirus 2, rotavirus SA11, and bacteriophages T2 and MS2. The rate of virus inactivation was evaluated statistically with regard to conditions under which the vials were incubated and to the soil characteristics. The factors that were found to influence virus survival were temperature, soil moisture content, presence of aerobic microorganisms, degree of virus adsorption to the soil, soil levels of resin-extractable phosphorus, exchangeable aluminium, and soil pH. Overall, temperature and virus adsorption to soil appeared to be the most important factors affecting virus survival. PMID- 6257162 TI - Chlorine resistance of poliovirus isolants recovered from drinking water. AB - Poliovirus 1 isolants were recovered from finished drinking water produced by a modern, well-operated water treatment plant. These waters contained free chlorine residuals in excess of 1 mg/liter. The chlorine inactivation of purified high titer preparations of two such isolants was compared with the inactivation behavior of two stock strains of poliovirus 1, LSc and Mahoney. The surviving fraction of virus derived from the two natural isolants was shown to be orders of magnitude greater than that of the standard strains. These results raise the question whether indirect drinking water standards based on free chlorine residuals are adequate public health measures, or whether direct standards based on virus determinations might be necessary. PMID- 6257163 TI - Rotavirus concentration from cell culture harvests: trypsin treatment followed by hydroextraction. AB - An 80- to 150-ml amount of calf or simian rotavirus-containing cell culture harvests of MA-104 cells were treated with 50 microgram of trypsin per ml and hydroextracted overnight (4 degrees C) with polyethylene glycol 6,000. The concentrate was resuspended in 8 to 10 ml of tryptose phosphate broth and plaque assayed. Between 85 and 97% of the input virus could be recovered with a concentration of up to 15-fold. PMID- 6257164 TI - Behavior of pathogenic bacteria in the oyster, Crassostrea commercialis, during depuration, re-laying, and storage. AB - Oysters (Crassostrea commercials) harvested from major cultivation areas within the state of New South Wales, Australia, were commonly contaminated with low levels of the food-poisoning organisms Bacillus cereus, Clostridium perfringens, and Vibrio parahaemolyticus. Salmonella was found in oysters on only one occasion. These bacteria were cleansed from oysters during oyster purification by re-laying in a non-polluted waterway. Oysters were laboratory contaminated to levels in excess 1,000 cells per g with either B. cereus, C. perfringens, V. parahaemolyticus, Salmonella typhimurium, or S. senftenberg. These species were cleansed from such oysters during purification in a laboratory depuration unit that used ultraviolet light for sterilizing the depuration water. Escherichia coli was also cleansed from oysters under the same re-laying or depuration conditions so that its measurement alone could be used to indicate the cleansing of the above pathogenic species. The levels of these bacteria were also measured during the storage of oysters under conditions that occur during marketing. While B. cereus counts remained relatively stable during storage, the Salmonella spp. gradually decreased in numbers and C. perfringens rapidly died off. V. parahaemolyticus counts increased slightly during the first 4 days of storage, after which decreases occurred. PMID- 6257165 TI - [Immunresponse of Syrian hamsters, mice and rabbits after intranasal or subcutaneous application of different parainfluenza-3-vaccine-viruses (author's transl)]. PMID- 6257166 TI - [Morphological and virological studies on the virus cell relationship in various vertebrate cells infected with avian myeloblastosis virus (author's transl)]. PMID- 6257167 TI - [The effect of antibiotics on the synthesis of humoral antibodies in the mouse (author's transl)]. PMID- 6257169 TI - Modification of the reactive sulfhydryl of bacterial luciferase with spin-labeled maleimides. PMID- 6257168 TI - A kinetic comparison of cardiac glycoside interactions with Na+,K+-ATPases from skeletal and cardiac muscle and from kidney. PMID- 6257170 TI - Proton magnetic resonance studies of cytochrome c peroxidase: pD dependence of the isotropically shifted resonances. PMID- 6257171 TI - The significance of light activation of enzymes during the induction phase of photosynthesis in isolated chloroplasts. PMID- 6257172 TI - Interaction of epidermal growth factor with adult rat liver parenchymal cells in primary culture. PMID- 6257173 TI - Isolation and properties of somatic and testicular cytochromes c from rat tissues. PMID- 6257174 TI - Investigation of the pH dependence of proton uptake by porcine heart mitochondrial malate dehydrogenase upon binding of NADH. PMID- 6257175 TI - Primary structure of yeast cytochrome c peroxidase. I. Chemical characterization of the polypeptide chain and of tryptic and chymotryptic peptides. PMID- 6257176 TI - Primary structure of yeast cytochrome c peroxidase. II. The complete amino acid sequence. PMID- 6257177 TI - Control of glycolysis and lipogenesis in the liver by glucagon at the phosphofructokinase-fructose 1,6-diphosphatase site. PMID- 6257178 TI - Inhibition of intracellular protein degradation by pepstatinyl, poly(L-lysine), and pepstatinyl-poly(L-lysine). PMID- 6257179 TI - Characterization of multiple charge isomers of the inhibitor protein of the cyclic AMP-dependent protein kinase from bovine heart and rabbit skeletal muscle. PMID- 6257180 TI - Regulation of rat liver phosphofructokinase by glucagon-induced phosphorylation. PMID- 6257181 TI - The lack of direct coupling between ATP-ADP translocase and creatine phosphokinase in isolated rabbit heart mitochondria. PMID- 6257182 TI - Does copper-D-penicillamine catalyze the dismutation of O2-? PMID- 6257183 TI - Familial variant of dermatofibroma with malignancy in the proband. AB - Multiple fibrous histiocytomas of the dermis (dermatofibromas) were found in six males of one family. A number of the tumors fell within the histologic patterns commonly encountered in dermatofibromas, but some were unusually large and others were cytologically atypical. In addition, the proband died of a malignant fibrous histiocytoma of the lung. We believe that this is a syndrome and a familial variant of a common dermal entity. PMID- 6257184 TI - Hidradenoma papilliferum of the eyelid. PMID- 6257185 TI - Summer diarrhoea in African infants and children. AB - Of 70 black South African infants and children with acute summer diarrhoea, 30 (43%) were infected with enteropathogenic serogroups of Escherichia coli (EPEC), 13 (19%) with enterotoxigenic Gram-negative bacilli, 12 (17%) with Salmonella sp., 6 (9%) with Shigella sp., and 3 (4%) with rotaviruses. 13 (19%) patients were infected simultaneously with more than one enteropathogen, and no pathogen was detected in 22 (31%). In addition, 6 (15%) of 41 unselected patients were excreting Campylobacter fetus. Of 30 age-matched controls drawn from the same population, 5 (17%) were infected with EPEC serotypes, and 1 each with Salmonella sp. and rotavirus. This study stresses the polymicrobial nature of paediatric diarrhoea in a developing community and shows the continued importance of EPEC in this setting. PMID- 6257186 TI - Cigarette smoke exposure in vivo increases cyclic GMP in rat lung. AB - The enzyme guanylate cyclase is stimulated to produce cycle guanosine 3',5' monophosphate (GMP) when lung tissue is exposed to cigarette smoke in vitro. These experiments tested whether in vivo exposure in rats to cigarette smoke produces a similar response. Adult rats were anaesthetized with pentobarbital and ventilation with mixtures of air and cigarette smoke at 10 cm H2O inspiratory pressure was achieved after a tracheotomy was performed. Lung tissue samples were taken at intervals during 20 min exposure period and analyzed for levels of cyclic adenosine 3', 5'-monophosphate (AMP) and cycle GMP. Blood carboxyhemoglobin (COHb) levels at 5 min and 15 min of exposure showed high, but sublethal levels of COHb. lung tissue cAMP was unchanged with this exposure, but cGMP levels rose dramatically. Rat lungs showed no changes related to ventilation under similar conditions in the absence of smoke. This observed response of cGMP to cigarette smoke may represent an important pulmonary defense mechanism. PMID- 6257187 TI - Regulation of LH/HCG receptors during the ovarian cycle in rats. AB - The number of LH/HCG receptors varied during the ovarian cycle. Most 125I-HCG was bound in the diestrous II stage, least amounts of free binding sites were detectable in estrous. Bromocriptine, an inhibitor of prolactin secretion, suppressed the cyclic variations in free LH/HCG receptors. From this finding it is concluded that LH/HCG receptors of the corpus luteum of the cycle are occupied by LH just once and then degraded. The variations in the number of free LH/HCG receptors are probably due to the synthesis and degradation of only luteal receptors. PMID- 6257189 TI - [Granular cell tumor of the common bile duct (author's transl)]. PMID- 6257188 TI - [Cytoplasmic localization of mammary carcinoma steroid receptors by histofluorescence (author's transl)]. PMID- 6257190 TI - [Granular cell tumors : granulocellular schwannomas? Histo-enzymological and ultrastructural study (author's transl)]. PMID- 6257191 TI - The susceptibility of Lutzomyia longipalpis (Lutz and Neiva), Diptera, Psychodidae, to artificial infection with three viruses of the Phlebotomus fever group. PMID- 6257192 TI - Multiplication of bluetongue virus in culicoides nubeculosus (Meigen) simultaneously infected with the virus and the microfilariae of Onchocerca cervicalis (Railliet & Henry). PMID- 6257193 TI - Treatment of acute and chronic congestive heart failure by vasodilator-afterload reduction. PMID- 6257194 TI - Neuropsychiatric manifestations of patients with Cushing's syndrome. Relationship to cortisol and adrenocorticotropic hormone levels. AB - Thirty-five consecutive patients with Cushing's syndrome were studied prospectively before treatment. A consistent constellation of neuropsychiatric disturbances was found, including impairments in affect (depressed mood and crying), cognitive functions (decreased libido and insomnia). Thirty-four percent of patients were rated as having a mild, 26% a moderate, 29% a severe, and 11% a very severe psychiatric disability. A statistically significant relationship was found between the overall neuropsychiatric disability rating and cortisol and adrenocorticotropic hormone (ACTH) levels. Patients with adrenal adenomas with high cortisol but low ACTH levels did not have as severe a neuropsychiatric disability. PMID- 6257195 TI - [Concentration of viruses and virus-specific antigens by ultrafiltration with membranes developed in the GDR]. AB - A cellulose acetate membrane, jointly developed by the Institute of Dairy Research in Oranienburg and the Institute of Polymer Chemistry in Teltow, was successfully used to concentrate by factors between ten and 40 virus suspensions of transmissible gastroenteritis and foot and mouth disease with a protein level of roughly 0.1 per cent in a 400-ml cell with magnetic agitation. The procedure took about two hours, with working pressures being between 0.2 MPa and 0.4 MPa. Virus yield in the residue was 100 per cent. Good results were obtained also from virus-specific antigens and calibration proteins with molecular weights of somewhat in excess of 50,000 Dalton. PMID- 6257196 TI - A hypothesis of thyroid-catecholamine-receptor interaction. Its relevance to affective illness. AB - Recent prospective studies suggest that thyroid state plays a role in affective disorders. A lack of thyroid hormones can lower the threshold for depression; an excess can contribute to a state of tense dysphoria. Thyroid function in some persons also appears to influence the course of affective disorders. Adequate mobilization of thyroid hormones favors recovery from depression; excess mobilization increases the risk of mania in vulnerable individuals. Although other mechanisms may be involved, evidence suggests that the modulation by thyroid hormones of the beta-adrenergic receptor response to catecholamines may contribute to these effects. Norepinephrine stimulates such receptors; thyroid hormones increase their ability to receive stimulation. The plausibility of such interactions between catecholamines and thyroid hormones occurring in the CNS is strengthened by their common origin in the amino acid tyrosine and by their synergism in many metabolic processes. PMID- 6257198 TI - Nuclear magnetic resonance at low temperatures in lyophilized and non lyophilized normal and tumoral tissues. III. Study of the solid--fluid interface. AB - Adsorption water on lyophilized and non-lyophilized, normal and malignant tumoral tissues was studied by nuclear magnetic resonance. Comparative study of variations in the proton signal amplitude (A) and the water proton line width (delta v) at temperatures within the 0 degree to --40 degrees C range showed: (a) The identical behaviour of the proton signal amplitude of water adsorbed on normal rat tissues (liver, skeletal muscle). (b) Similar behaviour of the amplitude in malignant tumoral tissues and hepatic embryonic tissue. (c) Dependence of the relative variation of the resonance line width at --25 degrees and --5 degrees C upon hydration of the sample suggested that there was no difference between malignant and normal tissues at the level of the macromolecular structure-adsorption water interface. PMID- 6257197 TI - Immunity to Friend virus complex: analysis of protection with a sarcoma virus pseudotype. AB - To specify the mechanism whereby inoculation of sarcoma viruses protects against leukemia development by leukoviruses, several experiments were performed using Friend virus complex (FVC) and MSV-F, a sarcoma virus pseudotype prepared in vitro with FVC as source of the helper component. The sarcomatous lesions induced by MSV-F were self-limited, irrespective of dose and route of inoculation and protected against the progressive, lethal erythroleukemia induced fy FVC. The sera of MSV-F primed mice had high FVC-neutralizing titers, Out of 3 properties titered in FVC, immunogenicity, XC-syncytium-forming activity and lethality, the frmer two were retained at high titers in MSV-F, while lethality was almost entirely lost: the dose-range between lethal immunizing dilutions was 2-3 logs broader for MSV-F than for FVC. It is postulated that the lethal, early erythroleukemia inducing component (Spleen Focus Forrming Virus) is rapidly lost from FVC upon in vitro propagation. The rescued MSV-F would carry a hightitered, immunogenic and Xc-syncytium forming component (Lymphatic Leukemia Virus), thus behaving as an immunogenic virus of limited pathogenicity. PMID- 6257199 TI - Virus-viral co-cancerogenesis and the other viral interactions. AB - The article presents the data obtained by the authors in studies of virus-viral co-cancerogenesis, the interaction between some non-oncogenic viruses and well known oncogenic viruses, the results of co-cancerogenic effect Marek's disease herpesvirus with the avian leukemia virus and the possibility of phenotype mixing between oncornaviruses belonging to different species in nature. PMID- 6257200 TI - Studies in AMV DNA. I. Physical properties and sequence composition of DNA present in AMV virions (AMV DNA). AB - The basic physical properties of AMV DNA (labeled with 3H-thymidine) as well as sequence homology between 3H-AMV DNA and viral or host cell genomes were investigated. It was found that native AMV DNA is in part single-stranded (20% of the total DNA). Using CsCl density gradient centrifugation AMV DNA was separated into two bands with buoyant densities of 1.702 g/cm3 (L-AMV DNA) and 1.722 g/cm3 (H-AMV DNA) in the peak fractions. Corresponding melting temperatures were estimated to be 82.0 degrees C and 81.3 degrees C for L- and H-AMV DNA, respectively. Hybridization experiments revealed that AMV DNA is not complementary to the AMV genomic RNA but complementary prevalently to the sequences with low frequency of repetition and to the unique sequences of the myeloblast genome. These unique sequences, comprising about 40% of the total 3H AMV DNA, were not detected in the nuclear DNA of leukosis-free chicken embryo fibroblasts. After infection of embryo cells with AMV the extent of hybridization in the region of unique sequences rose roughly by 20%. Renaturation of thermally denatured 3H-AMV DNA using the phenol emulsion reassociation technique was observed. The results suggest that AMV DNA is composed of a number of different special sequences of the host genome. PMID- 6257201 TI - Studies in AMV DNA. II. A possible origin of DNA present in AMV virions (AMV DNA). AB - Some properties of cytoplasmic nonmitochondrial DNA--cyt DNA--from chicken leukemic myeloblasts were determined and compared with corresponding characteristics of AMV DNA. Our results indicate that cyt DNA and AMV DNA molecules are akin with respect to their specific radioactivities, sedimentation behaviour and melting profiles. Furthermore, the partial lack of sequence reiteration of both cyt and AMV DNAs distinguished them from the nuclear myeloblast DNA. It is concluded that cyt DNA of myeloblasts represents a set of distinctive cellular sequences some of which are liberated into the extracellular environment and are found in the AMV preparations. PMID- 6257202 TI - RSV-transformed mammalian cells: an analysis of RNAs specific for exogenous and endogenous viruses. AB - A marked decrease in expression of RSV-specific sequences was observed in cryptovirogenic RSV-transformed RVP3 murine cells during passaging. Simultaneously an increase in expression of sequences specific for C-type murine viruses was observed both in these cells and other RSV-transformed murine cells. No activation of C-type viral genome was detected in spontaneous murine lung tumors and in methylcholanthrene-induced murine tumors. Four types of virus specific RNAs were found in XC cells: the 30--35 S, the 26--28 S, the 21--23 S and the 15--18 S type. The 9--14 S RNA was the dominant species of RSV-specific RNA in TWERC cells. PMID- 6257203 TI - Long-term persistence of transformation-defective mutants of subgroup C in chickens and ducks inoculated early in life. AB - Three transformation-defective mutants derived from avian sarcoma viruses of subgroup C were injected intraembryonally and neonatally into leukosis-free chickens. Viruses persisted in the blood of all inoculated birds tested for 43 to 163 days after hatching. Similarly, these viruses persisted over more than one year in ducks injected intraembryonally. In two tested ducks virus titres in blood plasma were determined and it was found that they reached 10(2) and 10(3) infectious units per ml. The significance of td mutant persistence, particularly in relation to a possible recombination with chicken and duck src sequences, is discussed. PMID- 6257204 TI - Genesis of 1,2-dimethylhydrazine-induced colon cancer. A light and electron microscopic study. AB - Rats treated with 1,2-dimethylhydrazine (DMH) exhibited colonic mucosal dysplastic foci prior to the development of tumors. Ultrastructurally, these, as well as the cancers that subsequently developed, were characterized by alterations in plasma membranes and an increase in cytoplasmic ribosomal particles, principally in stem cells and their absorptive derivatives. Rare Kulchitsky cells appeared preserved, but the mucin-producing or goblet-cell elements were compressed and atrophic. In addition, nuclear aberrations were more pronounced in the cancer than in the dysplastic foci. The principal ultrastructural difference between the so-called well-differentiated and mucinous forms of DMH-induced cancers was the presence of frequent intracytoplasmic lumens in the mucinous form. Such structures represented the analogues of signet ring cells observed by light microscopy. This experimental model of human colonic cancer shows that the mucosal stem-cell and dysplastic lesions represent their cytogenetic and histogenetic progenitors. PMID- 6257205 TI - A human model for study of blood-vascular wall interactions. Effects of enzymatic treatment of intima. AB - A human umbilical cord vein model was used to study the interaction of human blood with vein intima after treatment with certain enzymes. Treatment of the intima with neuraminidase produced little in the way of morphologic change, and studies showed no increase in the retention of platelets labeled with chromium 51. Treatment of vein intima with collagenase produced severe morphologic changes, with exposure of coarse and fine subendothelial fibers, but with the retention of platelets little enhanced, as determined morphologically or radiometrically. On the other hand, treatment of vein intima with trypsin resulted in loss of endothelium in some areas, with exposure of coarse subendothelial fibers that produced a marked increase in platelet retention, as determined both morphologically and radiometrically. Exposure of the vein intima to thrombin produced apparent contraction of endothelial cells, with focal exposure of subendothelium and platelet adhesion. PMID- 6257206 TI - Quantitative measurements of human bone enzymes. AB - Up to now quantitative analysis of human bone enzymes is a part of osteology which is not evaluated sufficiently. The lack of standardized methods, fresh bone and reliable methods of bone disintegration seem to impede these experiments mainly. The authors have elaborated a complex method for quantitative measurements of human bone enzymes and they describe the practical use of this method. The importance of quantitative bone enzyme measurements is pointed out. PMID- 6257207 TI - [The physiology and pathology of bile acid metabolism]. AB - The biochemistry and metabolism of bile acids are briefly described together with their importance in the maintenance of biliary homeostasis. An account is given os some situations in which such metabolism is impaired: in cirrhosis of the liver, an isotope technique was used to show a fall in cholic acid (expression of liver cell damage); in cholostasis, stress is laid on reduced bile acid synthesis and a simultaneous increase in sensitivity of the bile canicular epithelium to secretin stimulation. Lastly, evidence is produced to suggest that the diarrhoea which often recurs after extensive intestinal resection is secondary to an increase in intestinal AMPc cells induced by bile acids. PMID- 6257208 TI - Comparative study of effects of lead on the activity of erythrocyte pyrimidine 5' nucleotidase and delta-aminolevulinate dehydratase in vivo and in vitro. AB - The effect of lead on the activities of erythrocyte pyrimidine 5'-nucleotidase (Py5N) and delta-aminolevulinate dehydratase (ALA-D) was studied in the mice which were given ad libitum a drinking water containing lead of 10, 50 and 250 ppm, for 27 days. The erythrocyte Py5N activity was not decreased in all groups of lead-exposed mice. However, the erythrocyte ALA-D activity was markedly decreased in the groups exposed to 50 and 250 ppm lead. These data indicate that erythrocyte ALA-D is more sensitive than Py5N to lead in vivo. On the other hand, from the in vitro study, it was demonstrated that the human erythrocyte Py5N is moderately inhibited by zinc and tin, and markedly by mercury, cadmium, silver, copper, and lead, at 10(-4) molar concentrations. In addition, it was observed that the erythrocyte Py5N is most remarkably inhibited by mercury while the ALA-D by lead, among metals tested. PMID- 6257209 TI - The presence of hepatic intramitochondrial crystalline inclusions in polybrominated biphenyl-treated mice. AB - Electron microscopic study of livers from mice fed 167 ppm polybrominated biphenyl (PBB) revealed mitochondrial abnormalities which consisted of both alterations in size and the formation of crystalline-like inclusions within the mitochondrial matrix. These inclusions appeared as parallel arrays of rods and were found in elongated mitochondria which contained few cristae. The findings are briefly described and the possible significance of such inclusions in relation to mitochondrial aberrations are discussed. PMID- 6257210 TI - Pruritus as a sign of systemic disease. Report of metastatic small cell carcinoma. PMID- 6257211 TI - Herpesviruses and parkinsonism. Herpes simplex virus types 1 and 2, and cytomegalovirus antibodies in serum and CSF. AB - Antibodies against herpes simplex virus (HSV) types 1 and 2 and cytomegalovirus (CMV) were assayed with a microindirect hemagglutination (IHA) test in the serum of 67 pairs of patients with Parkinson's disease and controls. Cerebrospinal fluid from 30 pairs was assayed. All patient and control serum was tested with a radioimmunoassay (RIA) for antibodies against HSV type 1 subunit antigens. Serum IHA antibody level against HSV type 1 was increased in patients with Parkinson's disease and RIA antibody levels against the same viral antigen were significantly higher in the patients than controls. Herpes simplex virus type 2 and CMV serum antibodies were equal in the patient and control groups. Most of the CSF samples tested negatively for IHA; small and comparable numbers of the patients and controls had low antibody levels against HSV and CMV antigens. PMID- 6257212 TI - Recurrent herpes zoster encephalitis. A complication of systemic lupus erythematosus. AB - A middle-aged woman had five discrete episodes of herpes zoster. The first attack consisted of uncomplicated herpes zoster ophthalmicus. The subsequent four episodes involved thoracic, cervical, and finally sacral dermatomes and were complicated by myelitis or encephalomyelitis. During the most recent attack, while she was receiving corticosteroids, varicella-zoster virus was cultured from the CSF. In addition, the patient had strong evidence of systemic lupus erythematosus, with a history of Raynaud's phenomenon, migratory arthralgia, and unexplained anemia before the first attack of zoster with subsequent development of a positive lupus cell preparation and elevated antinuclear antibody levels. PMID- 6257213 TI - Aicardi's syndrome: are corticosteroids teratogens? PMID- 6257214 TI - cAMP and cGMP in the human parotid saliva. AB - Human parotid saliva was revealed to contain considerable amounts of cAMP and cGMP. On sour lemon drop stimulation, the salivary cyclic nucleotides concentration decreased and the cyclic nucleotides secretory rate increased in close relationship with the salivary flow rate in control subjects. On feeding, both cAMP concentration and secretory rate increased significantly in control subjects. Parotid saliva from a patient of Sjogren's syndrom was revealed to have a significantly higher of cGMP concentration than those from control subjects. Saliva derived from the malignant tumor of the parotid gland was revealed to have a higher cGMP concentration and a lower cAMP concentration than the healthy site. From these findings, the possibilities of the clinical usefulness of studying salivary cyclic nucleotides were discussed. PMID- 6257216 TI - Fluoride, cAMP production and enzyme inhibition. PMID- 6257215 TI - Double primary synchronous and metachronous cancer of the larynx and hypopharynx with dissimilar histology. Five case reports and review of the literature. AB - Five cases of double primary synchronous and metachronous cancers of the larynx and hypopharynx with dissimilar histology encountered at the Section of Pathology of the Department of Otolaryngology of Padua University from 1966 through 1979 are reported. The pathogenesis of these double primary malignancies is discussed, and in particular stress is laid on the perhaps not purely coincidental association of squamous cell and oat cell carcinoma of the larynx and hypopharynx. Furthermore, a thorough review of the literature is made on the reported cases of two primary simultaneous or metachronous malignancies of the larynx and hypopharynx of different histological type. PMID- 6257217 TI - An immunohistochemical study of secretagogue-induced secretion of epidermal growth factor in the submandibular salivary glands of mice. AB - Routine histological and indirect immunofluorescence techniques were used to examine the histological details of changes in the distribution of epidermal growth factor (EGF) in the submandibular salivary glands of mice during secretion. Comparisons were made bewteen glands of normal mice and those of mice given one of a number of secretagogues at various times prior to sampling. Normal submandibular salivary glands in male mice had an extensive system of convoluted granular tubules (CGT), the cells of which contained EGF. When adrenaline of alpha-phenylephrine was administered, the CGT cells degranulated, and there was a concomitant loss of intracellular EGF-positive immunofluorescence. The excretory ducts were engorged with immunofluorescent material, indicating secretion of EGF into saliva, while the ductal cells themselves remained EGF-negative. The degranulation response could be blocked by phentolamine, but not by propranolol, and no changes in EGF distribution followed the administration of pilocarpine. It was concluded that EGF is secreted, at least partly into the saliva, following an alpha-adrenergic response, and that this occurs with degranulation of the cells of the CGT. PMID- 6257219 TI - Spray vaccination of chickens using infectious laryngotracheitis virus. AB - Day-old chickens were vaccinated with the SA2 strain of infectious laryngotracheitis vaccine using a coarse spray and 14-day-old chickens were vaccinated using a coarse or a fine (Turbair Vaccinair 240) spray. The Conjunctiva was the most common site of infection in all cases but this almost invariably led to involvement of the nasolacrimal ducts. Other sites in the nasal cavity were affected less frequently. The clinical consequences of infection in day-old chickens were too severe for field use but the mortality (0 to 1.4% in different experiments) in 14-day-old chickens may be acceptable in some circumstances although about 9% developed infection of the trachea. It is concluded that a less pathogenic vaccine is needed if spray vaccination with ILT is to be recommended as a routine procedure particularly for day-old chickens. PMID- 6257218 TI - The clinical response of gnotobiotic calves, pigs and lambs to inoculation with human, calf, pig and foal rotavirus isolates. AB - The infectivity, pathogenicity and immunogenicity of 5 human, 6 calf, 2 pig and 2 foal rotavirus isolates were studied in gnotobiotic calves, piglets and lambs. Three of the human isolated produced subclinical infection in newborn gnotobiotic piglets and the piglets developed neutralising antirotavirus antibody. When challenged with pig rotavirus 2 weeks later, the piglets did not develop diarrhoea, but rotavirus was detected in the faeces. In contrast, piglets inoculated with the other 2 human isolates failed to show evidence of infection and there was no specific antibody detected. These piglets developed diarrhoea when challenged 2 weeks later with pig rotavirus. The 4 human isolated failed to infect gnotobiotic calves an lambs. PMID- 6257221 TI - Herpesvirus hepatitis in rat kangaroos. PMID- 6257220 TI - Antibodies to infectious bursal disease virus in poultry flocks in Western Australia. PMID- 6257222 TI - Hysterectomy in obstetric practice. AB - A 9-year review (1971-1979) is presented of patients undergoing hysterectomy in the course of pregnancy. The incidence was 1 in 1,044 pregnancies (34 in 35,506). The principal indications were ruptured uterus (9), postpartum haemorrhage (8), placenta accreta (5) and neoplastic trophoblastic disease (4). In spite of the high incidence of hysterectomy in our community, the procedure was undertaken during pregnancy with great reluctance and usually only as a life-saving procedure. PMID- 6257223 TI - Secondary amenorrhoea due to autoimmune ovarian failure. AB - A case of spontaneous premature menopause due to autoimmune ovarian failure is described. This report emphasises that this uncommon condition is important to diagnose because of its association with other autoimmune endocrine disorders including Addison's disease. In addition, in the present case, the marked increase in luteinizing hormone with relatively normal follicle stimulating hormone raises the possibility of a non-steroidal inhibitory feedback of follicle stimulating hormone. PMID- 6257224 TI - Phosphorylated proteins in Drosophila membranes. AB - Reversible protein modification-demodification in bacterial membranes has been shown to be an important mechanism for the adaptive behavior of bacteria in response to chemosensory stimuli. It has been suggested that the protein modification mechanisms might have wider functional implications and might form the basis for an understanding of complex phenomena such as information storage and retrieval. Phosphorylation of membrane proteins in the mammalian system is a well-documented phenomenon. Greengard and coworkers have shown that phosphorylation of a set of synaptic membrane proteins, collectively known as protein I is stimulated specifically in response to cAMP and calcium. We have explored the possibility of in vitro phosphorylation of proteins in membrane preparations obtained from Drosophila fly heads. Here we present a preliminary report of these studies. PMID- 6257225 TI - [The electrophoretic stability of galactose-1-phosphate-uridyltransferase (E.C.2.7.7.12) after aging under various methods of preservation]. PMID- 6257227 TI - Humoral and cellular immune response to varicella-zoster virus in children inoculated with live attenuated varicella vaccine. AB - Twenty-seven hospitalized children without a history of varicella were vaccinated with 500 plaque forming units of live attenuated varicella vaccine (Oka strain) and followed for four to five weeks at weekly intervals for the development of virus-specific cell-mediated immunity (CMI) and neutralizing (NT) antibody activity. These children had suffered from heterogeneous underlying diseases, such as acute leukemia, lymphoma, the nephrotic syndrome, and other chronic illnesses and were in various immunological states. Development of specific CMI, detected by lymphocyte transformation (LTF), was observed in 23 of the 27 children. The appearance of LTF activity in immunologically handicapped patients was delayed and/or rather suppressed compared with that of immunologically normal patients. An antibody response was detected in 26 of the 27 children. All of the vaccinated patients were protected effectively against a subsequent outbreak of varicella in the ward. PMID- 6257226 TI - Prevention of varicella in urgent cases by passive transfer of vaccine-induced immunity. AB - For the purpose of preventing spread of infection to high risk children whose immunities were severely impaired by intensive chemotherapy or for some other reason, when cases of varicella occurred in a children's ward or in a family, healthy adults (mothers and a doctor) were immediately given live varicella vaccine, blood was collected from these adults 5 to 7 days after vaccination and the whole blood or plasma including the buffy coat was transferred in the high risk children. Subsequently the children showed little or no clinical reaction, and follow-up studies by the neutralizing test and skin test with varicella antigen indicated that their inapparent or subclinical varicella infection occurred in them and that their immunity to varicella was lasting. Skin tests with varicella antigen showed that booster reaction occurred in adults with a previous history of varicella as early as 5 to 7 days after vaccination. The cellular immunity thus induced in the donors may have played a role in preventing a clinical reaction in the high risk children. Thus passive transfer of vaccine induced immunity seems a convenient and effective method for preventing infection in subjects whose immune capacities are severely impaired. PMID- 6257228 TI - Spread of varicella in hospitalized children having no direct contact with an indicator zoster case and its prevention by a live vaccine. AB - Varicella spread from a child with zoster to a total of 3 susceptible infants in another room in a children's ward, although they had been strictly isolated. To prevent spread of the disease, the staffs and patients were doing their own washing and no source of natural infection could be found. The cases indicate that it is difficult to predict nosocomial varicella infection or to prevent spread of the disease simply by isolation in a children's ward. A total of 11 other children without history of varicella in the ward were given live varicella vaccine before or immediately after this event. None of these children developed symptoms of varicella and all the susceptible children who were vaccinated showed an antibody response. PMID- 6257229 TI - Studies on the polypeptides of varicella-zoster (V-Z) virus. II. Syntheses of viral polypeptides in infected cells. AB - Synthesis of varicella-zoster virus (VZV)-induced polypeptide was examined at intervals after infection by immunoprecipitation, SDS-polyacrylamide gel electrophoresis (PAGE) and fluorography. Human embryonic lung (HEL) cells were inoculated with VZV-infected cells at a ratio of about 1 infected cell to 5 uninfected cells and pulse-labelled with 35S-methionine or 14C-glucosamine. Under this experimental condition, virus-induced protein and glycoprotein began to appear 4 to 6 and 18 to 20 h after infection, respectively, and a capsid protein (MW 145,000) was prominent 18 h after injection. The synthesis of these proteins reached maxima at 46 to 48 h after infection. In all, 34 polypeptides and 10 to 13 glycoproteins with molecular weight of 145,000 to 22,000 and 115,000 to 38,000, respectively, were detected. A few polypeptides (MW 130,000, 95,000, 72,000) were detected in infected cells treated with phosphonoacetic acid (PAA) at an early stage of infection. Proteins and glycoproteins of virion of VZV were analyzed by immunoprecipitation with antisera against partially purified virion of VZV. At least 12 polypeptides with MW of 145,000 to 35,000 and 7 glycoproteins (MW 105,000, 90,000, 84,000, 72,000, 70,000, 60,000 and 56,000) were identified. A polypeptide with a molecular weight of 145,000 was considered to be the major capsid protein. PMID- 6257230 TI - Cyclic nucleotide-independent protein kinases bound to cytoplasmic and nuclear polyribosomes in non-infected and adenovirus-infected HeLa cells. AB - Cyclic nucleotide-independent protein kinase activity bound to cytoplasmic and nuclear polyribsomes from non-infected and adenovirus-infected HeLa cells was compared. The enzymes catalysed the incorporation of phosphate from gamma-(32)P labelled ATP or GTP into acid-precipitable material in the absence of exogenous substrates. Their activity was not affected by cyclic AMP or cyclic GMP and was not inhibited by a cyclic nucleotide-dependent protein kinase-inhibitor protein. The kinases are tightly bound to polyribosomes of either origin from infected and non-infected cells, since treatment with 0.5m-NaCl did not dissociate the activity. The enzymes and the enzyme-associated endogenous substrates of cytoplasmic polyribosomes are significantly different from those of the nucleus, and adenovirus infection of the cells did not alter the nature of the enzymes or the substrates at 18-20h after infection. Nuclear kinases catalysed 3-4-fold more phosphate incorporation than did the cytoplasmic kinases. They did not phosphorylate endogenous substrates in the cytoplasmic preparations, and vice versa, which suggests that such substrates for cytoplasmic and nuclear kinases are specific. Polyacrylamide-gel electrophoresis of the phosphorylated proteins revealed the presence of a higher number of endogenous substrates in the nuclear preparation. The nuclear kinases phosphorylated all histones from HeLa cells, but the cytoplasmic ones phosphorylated predominantly the histone of mol.wt. 12000. Bovine heart kinase phosphorylated several low-molecular-weight cytoplasmic proteins and no nuclear proteins. With a DEAE-cellulose column either enzyme activity could be resolved into a number of peaks. The substrate specificities of these peaks indicate that there are at least two different forms of the enzyme in each preparation of polyribosomes. PMID- 6257231 TI - Phosphorylated and other modified forms of eukaryotic ribosomal protein S3 analysed by two-dimensional gel electrophoresis. AB - Proteins were isolated from the 40S ribosomal subunits of baby-hamster kidney fibroblasts and subjected to two-dimensional gel electrophoresis. When the cells were pretreated with cyclic AMP or 2-deoxyglucose a more basic derivative of ribosomal protein S3 or S3a was often observed, apparently similar to that previously reported to occur early in liver generation. This derivative was not a dephosphorylated form of protein S3, which protein does not appear to be phosphorylated in normal cells; nor did it correspond to the proteolytic fragment, S3b. It appears to be an oxidation product of protein S3 or S3a, as it can be eliminated by thorough reduction of the ribosomal protein before electrophoresis. In contrast with previous results with Krebs II ascites cells, starvation of baby-hamster kidney fibroblasts of glucose did not cause extensive phosphorylation of ribosomal protein S3. PMID- 6257232 TI - Electron paramagnetic resonance studies on Pseudomonas nitrosyl nitrite reductase. Evidence for multiple species in the electron paramagnetic resonance spectra of nitrosyl haemoproteins. AB - The e.p.r. spectra of reduced 14NO- and 15NO-bound Pseudomonas nitrite reductase have been investigated at pH 5.8 and 8.0 in four buffer systems. At pH 8.0, absorption spectra indicated that only the haem d1 was NO-bound, but, although quantification of the e.p.r. signals in all cases accounted for NO bound the the haem d1 in both subunits of the enzyme, the precise form of the signals varied with buffer and temperature. A rhombic species, with gx = 2.07, gz = 2.01 and gy = 1.96, represented in the low-temperature spectra seen in all the buffers was converted at high temperatures (approx. 200K) into a form showing a reduced anisotropy. Hyperfine splitting on the gz component of this rhombic signal indicated a nitrogen atom trans to NO and it is proposed that histidine provides the endogenous axial ligand for haem d1. At pH 5.8, absorption spectra indicated NO binding to both haems c and d1 and e.p.r. quantifications accounted for NO bound haems c and d1 in both enzyme subunits. The e.p.r. spectra at pH 5.8 were generally similar to those at pH 8.0 with respect to g-values and hyperfine coupling constants, but were broader with less well defined hyperfine splittings. As at pH 8, rhombic signals present in spectra at low temperatures were converted to less anisotropic forms at high temperatures. The results are discussed in relation to work on model nitrosyl-protohaem complexes [Yoshimura, Ozaki, Shintani & Watanabe (1979) Arch. Biochem, Biophys. 193, 301-313]. No. e.p.r. signal was observed from oxidized NO-bound Pseudomonas nitrite reductase at pH 6.0, over the temperature range 6-100K. PMID- 6257233 TI - Properties of pig synovial collagenase. AB - 1. Properties of a purified chemically activated form of pig synovial collagenase were examined and compared with a spontaneously active form of the enzyme. 2. The active enzyme has a specific activity of 53 000 units (microgram/min)/mg, a mol.wt. of 44 000 (by sodium dodecyl sulphate/polyarcylamide-gel electrophoresis in 2-mercaptoethanol) and pI 5.2 (by isoelectric focusing in polyacrylamide gels). 3. The activity has the characteristics of a metalloproteinase that degrades types I and III soluble or insoluble collagens in preference to type II, at an optimum pH of 6.5-8.5. 4. There is no detectable difference in these properties between the chemically activated and spontaneously active form of collagenase. PMID- 6257234 TI - Effect of hydrogen peroxide on spinach (Spinacia oleracea) chloroplast fructose bisphosphatase. AB - Thiol-treated spinach (Spinacia oleracea) chloroplast fructose bisphosphatase (EC 3.1.3.11) is severely inhibited by H2O2, whereas the freshly purified enzyme is little affected. Dithiothreitol reverses inhibition by H2O2, indicating that essential thiol groups are oxidized during H2O2 inactivation. A new role for the dithiol and thioredoxin systems that are operative in illuminated chloroplasts is proposed. PMID- 6257235 TI - Indicator enzyme assays. II. Adenylate kinase: application to human muscle biopsies and blood cells. PMID- 6257236 TI - Gluco- and mineralocorticoid receptors in human liver and kidney. PMID- 6257237 TI - Reconstitution of liposomes bearing platelet receptors for human von Willebrand factor. PMID- 6257238 TI - Interaction of a methylene diphosphonate analog of ADP with photosynthetic membranes of chloroplasts. PMID- 6257239 TI - A reversible spin conversion of cytochrome b5 at high temperatures. PMID- 6257240 TI - Identification of nitric oxide and nitrous oxide as products of nitrite reduction by Pseudomonas cytochrome oxidase (nitrate reductase). PMID- 6257241 TI - Immunochemical properties of unmodified and automodified poly(ADP-ribose) synthetases. PMID- 6257242 TI - A dual effect of Ca2+ on chloroplast fructose-1,6-bisphosphatase. PMID- 6257243 TI - A competitive antagonist of thyrotropin: asialo-choriogonadotropin. PMID- 6257245 TI - Inhibition of angiotensin converting enzyme with N alpha-phosphoryl-L-alanyl-L proline and N alpha-L-valyl-L-tryptophan. PMID- 6257244 TI - Interaction of polymyxin with vertebrate peripheral nerve axons. PMID- 6257246 TI - Induction of uterine peroxidase by hexestrol analogues. PMID- 6257247 TI - Effect of propranolol on prolyl hydroxylase activity in blood vessels of rats. PMID- 6257248 TI - Inhibition of the partially purified canine lung angiotensin I converting enzyme by opioid peptides. PMID- 6257249 TI - Identification of calcium pyrophosphate dihydrate crystals in asymptomatic metatarsophalangeal joints. PMID- 6257250 TI - Effects of dl-erythro-1-phenoxy-3-[(3,4-dimethoxyphenethyl)-amino]-butan-2-ol (PS 6) on rat heart sarcolemma. AB - Effects of dl-erythro-1-phenoxy-3-[(3,4-dimethoxyphenethyl)-amino]-butan-2-ol (PS 6) on ATPase and calcium binding activities of rat heart sarcolemma as well as adenylate cyclase of both sarcolemma and heart washed particles were studied under in vitro conditions. PS-6 at concentrations of 10(-7) mol/l or higher inhibited Na+-K+ ATPase and calcium binding activities significantly. The inhibition of calcium binding activity was dependent upon the concentration of calcium in the incubation medium with greater percentage inhibition seen at lower concentrations. While basal adenylate cyclase activity was not affected by 10(-7) -10(-4) mol/l, isoprenaline stimulated adenylate cyclase activity was inhibited by 10(-6) mol/l or higher concentrations of PS-6. At 10(-3) mol/l PS-6 a more generalized inhibitory effect was seen, with all parameters studied being inhibited. These results suggest that sarcolemma is one of the sites for the cardiac actions of PS-6. PMID- 6257252 TI - [Seroepidemiologic survey of the spread of rotavirus infection in a Milan population]. AB - The increasing evidence of involvement of Rotaviruses in the etiology of viral gastroenteritis prompted us to carry on a seroepidemiological survey on the population of Milan. The aim was to get informations on the extension of the circulation of these agents in our population. Utilising a commercial antigen prepared with the "Oslo" bovine strain, c.f.a. were titrated in sera from 575 healthy subjects (age 0 to > 60 years). Of them 232 were children under 4 years of age homogeneously distributed into 6 age classes: at birth, 1 day to 3 months, 4-6 months, 7-12 months, 13-24 months, 2-4 years. Rotavirus infection appears very common. About 80% of the subjects over 10 years have c.f.a. As it is shown by the sharp increase of antibody acquisition after an initial drop in the first 6 months (82% positive at birth and 41% between 4-6 months), the infection seems to occur very early in life, as much as the plateau is reached under 10 years of age. Moreover consistent antibody titers (greater than or equal to 1:32), which could indicate recent infection, first appear in babies 4 to 12 months of age. Such titres are absent in the adults and could be found again in people over 50. Positivity was significantly higher in females than in males (0.01 < P < 0.025). Transplacental c.f.a. passage was studied in paired sera of 37 women at delivery and in cord blood sera of their babies; 28 matched pairs of sera had coincidental titres, but there were additional three cord blood specimens with c.f.a. from newborns whose mothers were negative. PMID- 6257251 TI - Hemodynamic effects on aortic enzyme activities in spontaneously hypertensive rats. AB - Spontaneously hypertensive rats (SHRSP and SHR) and normotensive WKR were treated with hypotensive drugs, and arterial and venous enzyme activities were compared between treated and nontreated hypertensive groups. With the 4 month experiment, cholesterol esterase activity in the aorta from hypertensive SHRSP and SHR was significantly lower than that in the respective treated groups, whereas venous activity did not differ. By contrast, aortic NAGA activity was significantly higher in the hypertensive groups without any changes in venous activity. Acid phosphatase activity was unaltered. No effects of treatment were observed in the normotensive WKR. Accompanying a decrease in aortic cholesterol esterase, there was a marked increase in aortic cholesteryl esters accompanying hypertension. Aortic phosphodiesterase activity was significantly elevated in the hypertensive SHRSP and SHR compared with the respective treated groups. These results suggest that hypertension of long duration specifically decreased aortic cholesterol esterase activity with a consequent accumulation of cholesteryl esters in the aorta, and that this hemodynamic effect seemed to be partly mediated by cyclic AMP with an effect on the lysosomal membrane. These results could provide the biochemical bases for the relationship between hypertension and atherosclerosis. PMID- 6257253 TI - [Serodiagnosis of rotavirus infections in gastroenteritis of infants]. AB - We report the use of the line immunoelectroosmophoresis (LIEOP), a modification of the immunoelectroosmophoresis (IEOP), for the serodiagnosis of rotavirus infection, in comparison with the complement fixation test. We tested 17 paired and 29 single sera from hospitalized children affected by acute gastroenteritis; rotavirus had been searched in the stools both by electron microscopy and IEOP. The LIEOP showed seroconversion in all the 11 cases with positive stools and also in 5 out of 5 patients whose stool sample had been negative. Either we had not been able to detect the virus, or there was an intervening (nosocomial) rotavirus infection. All sera which were reactive by complement fixation with bovine rotavirus were also reactive by LIEOP. Some of the sera which reacted by LIEOP, both with the homologous and the heterologous antigen, were negative by complement fixation. PMID- 6257255 TI - [Cyclic AMP levels of peripheral lymphocytes in normal subjects and in patients with malignant neoplasms]. AB - Cellular cAMP was determined by the competitive protein binding assay (RIA method) in peripheral blood lymphocytes (PBL) isolated from 34 healthy blood donors and 31 tumor bearing patients. cAMP concentration in PBL from the cancerous patients was lower than the one found in healthy blood donors. Results are discussed in relation to the modification of immune reactivity induced by cancer. PMID- 6257254 TI - [Cross-over electrophoresis on cellulose acetate. A new method for rapid diagnosis of rotavirus infection]. AB - A new application of crossing-over electrophoresis on cellulose acetate (c.o.e.) in diagnosis of Rotavirus infections is described. The results are compared with those obtained in electron microscopy (e.m.). The main reasons for application of c.o.e. to routine virological diagnosis of Rotavirus infections are exposed. PMID- 6257256 TI - [Research on antiviral drugs. XIV. Synthesis and in vitro activity of certain thiosemicarbazones of 1-[(dialkylamino)alkyl]-2-chloro-3-formylindole]. PMID- 6257257 TI - Effects of dopaminergic receptor stimulation and opioid receptor blockade on GH incretion: preliminary findings. AB - The Authors describe the effects of CB 154 (2.5 mg, per os) and naloxone (0.4 mg, i.m) on GH levels in normal man serum. Preliminary results point to a clear potentiation of GH release when the opiate receptor blockade is added to a dopamine receptor stimulation. PMID- 6257259 TI - Photoperiodic rhythm of cAMP concentration in the rat's preoptic region. AB - Photoperiodic influences on cAMP concentrations in the preoptic region and parietal cortex of the rat were studied at different ambient temperatures. In the preoptic region a photoperiodic rhythm is present at control Ta (22 degrees C) and is strongly attenuated at low Ta (-10 degrees C). In the parietal cortex no statistically significant photoperiodic changes were observed either at control or low T(a)s. PMID- 6257258 TI - [Role of erythrocyte membrane lipids in the antagonism between vitamin A and D3]. AB - The "in vitro" lytic effect of retinol (35 microM) on various animal species erythrocytes is partially inhibited by cholecalcipherol. The inhibition observed is not related with reduction of retinol bound by erythrocytes membranes while it can be related with the amount of glycolipids not gangliosides of these cells. Instead, we have observed that the amount of retinol molecules bound to erythrocytes membranes and their haemolysis can be related with the gangliosides contents of red cells membranes. PMID- 6257260 TI - [Effect of vitamin D on cellularity and mechanical fragility of lysosomes: experiments on carrageenan granuloma cells]. AB - In rats daily treated with vitamin D3 (5 micrograms/g of body weight/d for 5 d), the subcutaneous charrageenan granuloma shows reduced cellularity, mesenchimal cells degenerative process, increased mechanical fragility of lysosomes, oedema and modified fibrillogenesis of stroma. These effects are related to vitamin D3 action on cytomembranes. PMID- 6257261 TI - Cefazolin experimental epilepsy: the effects of diazepam on the interictal ECoG. AB - Diazepam i.v. injected at the dose of 5 mg/Kg on a group of 14 Rhode-Island-Red chicks was able to antagonize and prevent the interictal EEG pattern induced by cefazolin i.v. Since cefazolin epilepsy is most probably dependent on a receptorial antagonism with GABA, these data seem to confirm the GABA-ergic nature of cefazolin epilepsy. PMID- 6257263 TI - [Extracranial metastasis of the glioblastoma multiforme--an ultrastructural studies (author's transl)]. PMID- 6257262 TI - [Pituitary adrenocortical response to high dose administration of betamethasone in neurosurgical patients (author's transl)]. AB - Using RIA technique, response patterns of ACTH-adrenocortical system to short term large dose corticosteroid therapy for neurosurgical patients were investigated. The subjects were consisted of 20 males and 13 females, ageing ranging from 10 to 60 years old. The subjects were divided into three groups according to mode of steroid administration. In the first group, 12 mg/day of betamethasone were administered for 5 days and cancelled without gradual reduction. In the second group, 12 mg/day of betamethasone were administered for 4 days and 6 mg/day of betamethasone were given for following 2 days. In the third group, 12 mg/day of betamethasone were administered for 3 days and gradual reduction of betamethasone was given for following 4-5 days. Response of plasma cortisol level to synthetic 18-ACTH were measured in all patients for 3 days after betamethasone administration cancelled. The results led to the following conclusion. 1) The second and third groups had not any clinical symptom after steroid cancelled, but one half cases of the first group had mild headache, nausea for 2 days after cancelled. 2) Recovery process of adrenocortical function in the second group is most rapidly, compared with that in other two groups. 3) In the postoperative steroid therapy in neurosurgery, it could be concluded that 4 days massive administration of steroid followed by stepwise reduction in 2 days would be functionally well tolerated by adrenocortical system. PMID- 6257265 TI - Cefotaxime treatment of patients who failed to respond to previous antibiotics. PMID- 6257264 TI - Advantages of technetium pyrophosphate scintigraphy over plasma enzyme analysis in estimation of anterior myocardial infarct size. AB - Infarct size was estimated by cumulative creatine kinase MB isoenzyme (CKMB-r) release and by technetium 99m stannous pyrophosphate (TcPYP) scintigraphy in 27 patients with acute anterior myocardial infarction. In eight patients, scintigraphy showed a central area of reduced tracer uptake surrounded by a peripheral rim of increased TcPYP accumulation ("doughnut" pattern). This appearance occurred only in large infarcts and the maximal scintigraphic area (51.3 +/- 2.8 cm2, mean +/- SEM) in this group was significantly greater than that in the remainder (28.1 +/- 2.5 cm2). Correlation between CKMB-r and maximal scintigraphic infarct area was moderate in the whole group. Exclusion of patients, however, with "doughnut" scintigrams in which correlation was very poor, resulted in substantial improvement in the remainder. It is suggested that in the central regions of large "doughnut" infarcts, reduced blood flow hinders the efflux of CKMB from the centre causing an underestimate of infarct size. Pyrophosphate scintigraphy appears to be more accurate than CKMB release in measuring the size of these large anterior infarcts. PMID- 6257266 TI - Hepatic malignancy after renal transplantation in an HBsAg positive patient. PMID- 6257267 TI - A trypsin-like neutral protease on Ehrlich ascites cell surfaces: its role in the activation of tumour-cell zymogen of collagenase. AB - Ehrlich ascites cells in mice have been shown to have a cell-surface trypsin-like neutral protease (TLNP) with proteolytic and beta-naphthylamidase activity. This activity is inhibited by low-mol.-wt inhibitors of trypsin but not by 11 high mol.-wt inhibitors of trypsin in free solution. We believe that lack of inhibition is due to protection given to the enzyme by the chemical environment of the cell surface. These cells were demonstrated to export a collagenase zymogen which has been shown to be activated by the cell-surface TLNP. When this protease was completely inhibited by low-mol.-wt inhibitors of trypsin, chymotrypsin was used to activate the collagenase zymogen exported by Ehrlich ascites cells. Examination of the products of collagenolysis at 15 degrees C demonstrated the expected 3/4- and 1/4-length alpha-chain fragments derived from monomeric collagen, confirming that collagenase was one of the enzymes responsible for lysis of the collagen fibrils in the test system. PMID- 6257268 TI - Effect of sex hormones on the response of mice to infection with Toxoplasma gondii. AB - Groups of male and female mice were gonadectomized and some implanted with a pellet of hexoestrol. Half of the animals in each group, including controls, were infected with a low-virulence strain of Toxoplasma gondii. The animals were killed 6 weeks after infection. Gonadectomy increased the relative thymic weight in both sexes, but more so in the male, and the paracortical area of the lymph node was enlarged, as was the thymus-dependent area of the spleen. Hexoestrol administration induced almost complete thymic atrophy and partial involution of the peripheral lymphoid tissues. Greater resistance to toxoplasmic infection was found in the gonadectomized mice than in controls of both sexes, possibly due to a better cell-mediated immunity in the gonadectomized animals. Overwhelming toxoplasmosis with increased mortality was found in the hexoestrol-treated mice after infection, probably resulting from a depression of cell-mediated immunity caused by hexoestrol. It is postulated that the cellular immune response is of greater importance than the formation of antibody in resistance to toxoplasmic infection. The role of the thymolmphatic--sex hormonal interrelation on the age- sex differences seen in the incidence of toxoplasmic lymphadenopathy is also discussed. PMID- 6257269 TI - Structure of pocks on the chorioallantoic membrane of fertile hens' eggs induced by herpes simplex virus types 1 and 2. AB - The fine structure of the chorioallantoic membrane of the fertile hen's egg infected with herpes simplex virus Types 1 and 2 was examined. Lesions induced by Type 1 virus were small, confined to the chorionic layer of the membrane and proliferative in nature with slight cellular infiltration into the mesoderm after incubation up to 7 days. With the Type 2 virus-induced pocks, reaction occurred throughout the thickness of the chorioallantoic membrane, and haemorrhages, necroses, ulceration and cellular infiltration of the mesoderm were prominent features. Inoculation of the membranes with Type 2 virus resulted in a large number of infected chorion cells compared with Type 1, whilst the cells of the mesoderm and blood vessels became infected with Type 2 virus but not Type 1. Two types of intranuclear granules, lattice structures in both nuclei and cytoplasm and virus particles with variously structured cores were found specifically in Type 2 infected cells. PMID- 6257270 TI - Establishment of a human hepatocellular carcinoma cell line releasing hepatitis B virus surface antigen. AB - A new hepatocellular carcinoma cell line, DELSH-5, derived from operative wedge biospy from a HBsAg sero- and tissue-positive patient, has been continuously propagated in vitro for nearly 22 months. The cells not only resemble hepatocytes on light and electron microscopic examination but also possess biosynthetic markers of the latter such as albumin and alpha-foetoprotein which were demonstrated in the supernatant medium as well as in the tumour cell cytoplasm. Karyology of cloned cells shows moderate aneuploidy, the major model chromosome number being 61. Though in the initial few passages HBsAg could not be detected, from the 13th passage onwards this viral component could be consistently demonstrated in small amounts in the concentrated supernatant medium by the macro and micro-ELISA techniques. The immunohistochemical techniques as well as electron microscopy have failed to demonstrate any virus component inside the cell. The cell line reported here is the third of its kind which will act as a useful laboratory model to obtain pure HBsAg and to study the hepatitis-B-virus- liver-cell interaction with particular reference to the oncogenic potential of the virus. PMID- 6257272 TI - Experimental ulcerative herpetic keratitis. I. Systemic immune responses and resistance to corneal infection. AB - The influence of previous infection with herpes simplex virus (HSV) on the susceptibility of rabbits to corneal inoculation of the virus was studied by means of the microtitration model for ulcerative herpetic keratitis. Systemic immune responses were assayed after skin and eye infections by means of the lymphocyte transformation (LT) and complement fixation (CF) tests. Both cutaneous and ocular primary infections resulted in cellular and humoral immune responses to HSV. In comparison to primary ocular infection, corneal disease in rabbits with previous skin infection ('secondary corneal infection') resulted in earlier initiation of cellular and humoral immune responses, while complement-fixing antibody titres reached a higher level. A previous cutaneous infection ('immunisation') provided considerable protection to the cornea and also accelerated recovery from corneal ulcerative disease. A correlation was observed between the initiation of the lymphocyte transformation response and the beginning of healing of corneal ulceration. A previous unilateral ocular infection induced an even higher degree of corneal resistance in that eye, and the opposite eye was protected to the same extent as by cutaneous immunisation. PMID- 6257273 TI - Micrococcus luteus endonucleases for apurinic/apyrimidinic sites in deoxyribonucleic acid. 1. Purification and general properties. AB - Two chromatographically distinct endonucleases from Micrococcus luteus, specific for apurinic and apyrimidinic sites (AP-endonucleases A and B), have been extensively purified and characterized. Both are free from DNA glycosylase, unspecific endonuclease, and phosphatase activities. The two enzymes behave as monomeric proteins of approximately 35000 daltons. In addition to their different chromatographic properties on CM-cellulose, P-cellulose, hydroxylapatite, and DNA -Sepharose, both AP-endonucleases can be distinguished as follows: AP endonuclease A has an isoelectric point of 4.8, shows a half-life of 4 min at 45 degrees C, reacts optimally at pH 7.5 and has a KM value of 2.3 X 10(-6) M. AP endonuclease B has a pI of 8.8, is more stable at 45 degrees C (half-life of 10 min), and reacts optimally between pH 6.5 and pH 8.5; its KM value is 3.7 X 10( 6) M. PMID- 6257271 TI - A comparison of the local and remote effects of basement-membrane regeneration in normal and diabetic rats. AB - If the capsule basement membrane of the lens is partially removed, the underlying epithelial cells of the normal rat, as the animal ages, continue to produce basement membrane as if the membrane had not been disturbed. The response of the diabetic animal is quite different and basement membrane synthesis is increased by about 60%. Furthermore, this increase also occurs although at a reduced rate in the opposite eye where basement membrane was undisturbed. This might be termed a "sympathetic effect" and appears to be due to a substance or substances dissolved in the aqueous humour of the sympathizing eye and arising from increased activity of cells producing basement membrane in the other eye. PMID- 6257274 TI - Micrococcus luteus endonucleases for apurinic/apyrimidinic sites in deoxyribonucleic acid. 2. Further studies on the substrate specificity and mechanism of action. AB - Two endonucleases specific for DNA-containing apurinic or apyrimidinic sites (AP endonucleases A and B) have been isolated from Micrococcus luteus and highly purified. These enzymes have no exonuclease activity. Both AP-endonucleases hydrolyze DNA-containing apurinic or apyrimidinic sites at the 5' end of the lesion, thus generating 3'-hydroxyl and 5'-phosphoryl end groups. DNA-containing pyrimidine dimers, introduced at low doses of UV, are not hydrolyzed, whereas DNA containing lesions, introduced at high doses of UV or by gamma irradiation are nicked by either AP-endonuclease. During hydrolysis of apurinic DNA, neither of the AP-endonucleases acts as a processive enzyme. PMID- 6257275 TI - Valyl-tRNA synthetase form yellow lupin seeds: hydrolysis of the enzyme-bound noncognate aminoacyl adenylate as a possible mechanism of increasing specificity of the aminoacyl-tRNA synthetase. PMID- 6257276 TI - An equilibrium study of the cooperative binding of adenosine cyclic 3',5' monophosphate and guanosine cyclic 3',5'-monophosphate to the adenosine cyclic 3',5'-monophosphate receptor protein from Escherichia coli. AB - The binding of adenosine cyclic 3',5'-monophosphate (cAMP) and guanosine cyclic 3',5'-monophosphate (cGMP) to the adenosine cyclic 3',5'-monophosphate receptor protein (CRP) from Escherichia coli was investigated by equilibrium dialysis at pH 8.0 and 20 degrees C at different ionic strengths (0.05--0.60 M). Both cAMP and cGMP bind to CRP with a negative cooperativity that is progressively changed to positive as the ionic strength is increased. The binding data were analyzed with an interactive model for two identical sites and site/site interactions with the interaction free energy--RT ln alpha, and the intrinsic binding constant K and cooperativity parameter alpha were computed. Double-label experiments showed that cGMP is strictly competitive with cAMP, and its binding parameters K and alpha are not very different from that for cAMP. Since two binding sites exist for each of the cyclic nucleotides in dimeric CRP and no change in the quaternary structure of the protein is observed on binding the ligands, it is proposed that the cooperativity originates in ligand/ligand interactions. When bound to double stranded deoxyribonucleic acid (dsDNA), CRP binds cAMP more efficiently, and the cooperativity is positive even in conditions of low ionic strength where it is negative for the free protein. By contrast, cGMP binding properties remained unperturbed in dsDNA-bound CRP. Neither the intrinsic binding constant K nor the cooperativity parameter alpha was found to be very sensitive to changes of pH between 6.0 and 8.0 at 0.2 M ionic strength and 20 degrees C. For these conditions, the intrinsic free energy and entropy of binding of cAMP are delta H degree = -1.7 kcal . mol-1 and delta S degree = 15.6 eu, respectively. PMID- 6257277 TI - Proton nuclear magnetic resonance studies of human immunoglobulins: conformation of the hinge region of the IgG1 immunoglobulin. AB - The conformation of the hinge region of the human IgG1 immunoglobulin has been investigated by making use of His-224 in the hinge region as a built-in proton nuclear magnetic resonance (NMR) probe. Human myeloma IgG1 (kappa) proteins Ogo and Yot and human polyclonal IgG were used along with their Fab and F(ab')2 fragments for the assignment of the His-224 signals. The titration behavior of His-224 of the intact IgG and the fragments was compared. It was shown that the titration curves for the intact IgG and the F(ab')2 fragments are identical and quite similar to those for the histidine residue in small peptides. By contrast, the Fab fragments give titration curves which are quite different from those for the intact IgG and the F(ab')2 fragments. Conclusions derived may be summarized as follows: (1) in the intact IgG1, the hinge peptide is fully exposed to the solvent and exhibits internal motion which is much more rapid than the Fab segmental motion with respect to Fc: (2) at the loss of the Fc portion of the IgG, the conformation of the hinge peptide in the F(ab')2 fragments remains unchanged; (3) the heavy--heavy interchain interactions involving the two disulfide bridges do not play the primary role in determining the conformation of the hinge region in the intact IgG as well as in the F(ab')2 fragments; (4) the existence of a small stretch of peptide fragment Thr-225--Leu-234 is essential in maintaining the conformation of the hinge region of the intact IgG and the F(ab')2 fragments; (5) in the Fab fragments, as a result of cleavage of a major portion of the hinge peptide, the C-terminal part of the heavy chain including His-224 is partially folded back toward the globular portion of the polypeptide chains; and (6) the hinge peptide in the Fab fragments still retains a degree of flexibility which is similar to that in the intact IgG and the F(ab')2 fragments. PMID- 6257278 TI - Magnetic resonance studies of apolipoprotein C-I nitroxide labeled or [13C]methyl enriched at methionine-38. AB - One of the three proposed lipid-binding regions of the human apolipoprotein C-I (apo-C-I) is an amphipathic helix which extends from residue 33 to residue 53 and includes a single methionine at sequence position 38. The involvement of the sequence around methionine-38 in phospholipid binding has been evaluated with paramagnetic and nuclear reported groups attached to the thiomethyl moiety. This moiety has been spin-labeled with N-(2,2,6,6-tetramethylpiperidinyl-1 oxy)bromoacetamide or 13C enriched with 13CH3I. As determined from its EPR spectrum, the nitroxide at Met-38 of apoC-I had a rotational correlation time (tau C) of 0.22 ns. When dimyristoylphosphatidylcholine (DMPC) was bound to the spin-labeled apoprotein, tau c increased to 0.35 ns, indicating decreased motion for the methionyl side chain. The line width (nu 1/2) and spin--lattice relaxation time (T1) for the thiomethyl resonance of 13C-enriched apoC-I in 10 mM phosphate buffer was 6.0 Hz and 320 ms, respectively. When the protein solution was made 1.6 M in Gdn-HCl, these values changed to 2.6 Hz and 970 ms, respectively. Upon addition of DMPC multilamellar liposomes to [13C]apoC-I in 1.6 M Gdn-HCl, the line width increased to 4.7 Hz and the T1 decreased to 380 ms. These results strongly suggest that methionine-38 of apoC-I resides in a region of the apoprotein which undergoes significant secondary and/or tertiary structural change upon disaggregation/unfolding in Gdn-HCl and upon interaction with phospholipid. PMID- 6257279 TI - Purification of plasminogen activator from Rous sarcoma virus transformed chick embryo fibroblasts treated with the tumor promoter phorbol 12-myristate 13 acetate. PMID- 6257280 TI - Identification of the six ligands to manganese(II) in transition-state-analogue complexes of creatine kinase: oxygen-17 superhyperfine coupling from selectively labeled ligands. AB - The complete coordination scheme for Mn(II) in transition-state-analogue complexes with creatine kinase has been determined by electron paramagnetic resonance (EPR) spectroscopy. Perturbations in the EPR spectra for Mn(II) due to superhyperfine coupling to 17O of selectively labeled ligands have been used to identify oxygen ligands in the first coordination sphere of the metal ion. The results show that in the complex of enzyme-MnADP-formate-creatine, Mn(II) is bound to oxygen ligands from both the alpha- and beta-phosphate groups of ADP, to an oxygen from the carboxylate group of formate, and to three water molecules. In the complex with thiocyanate replacing formate as the stabilizing anion, previous infrared experiments [Reed, G. H., Barlow, C. H., & Burns, R. A., Jr. (1978) J. Biol. Chem. 253, 4153-4158] indicated that the nitrogen from thiocyanate was bound to the Mn(II). The magnitudes of the 17O superphyperfine coupling constants from the O- ligands of the ADP phosphate groups and from the formate carboxylate are approximately equal and are larger than that for the water ligands. The symmetry of the zero-field-splitting tensor for Mn(II) indicates that the oxygens from the alpha- and beta-phosphate groups of ADP and the ligand donor atom from the anion occupy mutually cis positions in the octahedral coordination geometry. Water proton relaxation time measurements show that the three water molecules which are bound to Mn(II) are not in free exchange with the bulk solvent. Hence, an enclosed structure at the active site is indicated. The results suggest that for creatine kinase the activating metal ion is bound to all three phosphate groups in the transition state of the reaction. PMID- 6257281 TI - Adenosine di- and triphosphate transport in mitochondria. Role of the amidine region for substrate binding and transport. AB - A variety of base-modified nucleotide analogues was prepared and characterized as their alpha-32P- or U-14C-labeled compounds. Carrier-linked nucleotide binding and carrier-catalyzed exchange across the inner membrane of rat liver mitochondria were measured by using an inhibitor (atractyloside) stop method. Kinetic data of carrier-specific bound analogues were evaluated from Dixon plots and indicate that these analogues are competitive inhibitors for mitochondrial [14C]ADP uptake. Km and Vmax values for carrier-mediated uptake of nucleotide analogues were calculated from Lineweaver-Burk plots. By means of the analogues, a systematic mapping of the essential chemical and steric interactions between the transporter protein and the heterocycle of its substrate in the course of the binding as well as transfer step was achieved. Prerequisites for carrier-specific binding (recognition) are (A) an anti- or syn-positioned beta-glycosyl-linked heterocycle, (B) a nitrogen ring atom in position 7 for syn-structured analogues, and (C) an electron-rich region at the N(1) position, i.e., a permanent dipole moment oriented toward N(1) for anti-structured analogues. Additional requirements for subsequent transport catalysis are (A) a non-fixed anti positioned base moiety with a beta-glycosyl torsion angle of about -20 degrees, (B) a C(6)-positioned amino group, and (C) an unsubstituted C(2) atom. The complementary binding site at the carrier protein to the N(1)-C(6)(-NH2) amidine region is proposed to be represented by two juxtaposed and invariant bonding points, i.e., an asparagine or glutamine residue. PMID- 6257282 TI - Differential hormonal responsiveness of the ovalbumin gene and its pseudogenes in the chick oviduct. AB - We describe the isolation of recombinant phages from a chicken gene library which contain two genes designated X and Y. These two genes are linked to the ovalbumin gene (OV) in the order 5'-X-Y-ovalbumin-3' [Royal, A., Garapin, A., Cami, B., Perrin, F., Mandel, J. L., LeMeur, M., Bregegegre, F., Gannon, F, LePennec, J. P., Chambon, P., & Kourilsky, P. (1979) Nature (London) 279, 125-132]. Both genes contain multiple intervening sequences and share limited sequence homology with the authentic ovalbumin gene but are expressed in oviduct cells at different levels. X and Y hybridization probes were prepared in order to study the expression and the relative hormonal responsiveness of these three genes in chicken oviduct. The sequence specificity of the probes was demonstrated by Southern hybridization assays. Northern hybridization studies using the X and Y gene probes indicated the presence of putative precursor molecules in stimulated oviduct ribonucleic acid preparations, which differ in size from those observed for ovalbumin. R0t analysis has demonstrated that, similar to the ovalbumin gene, the level of X and Y gene transcripts is increased by the steroid hormone estrogen, but to varying degrees. The extent of hormonal responsiveness of the three closely related genes is in the order (normalized) relative to ovalbumin of OV:Y:X congruent to 100:10:1. Pulse-labeling studies of these three closely linked genes suggest that in estrogen-stimulated oviduct, the markedly different steady-state levels of the X, Y, and ovalbumin gene transcripts reflect their differential transcription rates. PMID- 6257283 TI - Characterization of calmodulin effects on calcium transport in cardiac microsomes enriched in sarcoplasmic reticulum. AB - Calmodulin prepared from red cell hemolysates was found to significantly increase Ca2+ uptake into cardiac microsomal preparations enriched in sarcoplasic reticulum in a dose-dependent manner. The stimulation of calcium uptake by calmodulin was additive to that stimulation produced by maximal stimulatory concentrations of adenosine cyclic 3',5'-phosphate (cAMP) dependent protein kinase and cAMP, indicating separate mechanisms of action and potentially different modulatory roles for these two systems in the control of calcium transport. K+ significantly decreased calmodulin stimulation of calcium uptake, while in the absence of calmodulin, K+ increased Ca2+ uptake. In the absence of K+, calmodulin increased Ca2+ uptake to levels observed at maximal K+ concentrations without calmodulin present. Na+ produced effects similar to those of K+ in this preparation both in the presence and absence of calmodulin. The effect of calmodulin on the intermediate steps of the (Mg2+,Ca2+)ATPase in cardiac sarcoplasmic reticulum was also investigated. Calmodulin was found to reduce the steady-state level of the Ca2+-dependent phosphoprotein (ECaP) and increase the (Mg2+,Ca2+)ATPase activity of this preparation. Dephosphorylation of ECaP in the presence of Tris-ATP (0.5 mM) was significantly stimulated by calmodulin. These studies indicate that calmodulin stimulates Ca2+ transport in cardiac sarcoplasmic reticulum by increasing the turnover rate of the transport process. PMID- 6257284 TI - Molecular cloning of the gene sequences of a major apoprotein in avian very low density lipoproteins. PMID- 6257285 TI - Spin-labeled cardiolipin: preferential segregation in the boundary layer of cytochrome c oxidase. PMID- 6257286 TI - Interaction of cytochrome c with reaction centers of Rhodopseudomonas sphaeroides R-26: determination of number of binding sites and dissociation constants by equilibrium dialysis. AB - The number of binding sites and dissociation constants of cytochrome c (horse heart) and cytochrome c2 (Rhodopseudomonas sphaeroides) to reaction centers of Rhodopseudomonas sphaeroides R-26 was determined by equilibrium dialysis. One binding site was found for both cytochromes. The dissociation constants (10 mM Tris-HCl, pH 8.0) were approximately 0.4 microM and approximately 1.0 microM for cytochrome c and cytochrome C2 respectively. Oxidized and reduced forms of both cytochromes bound to reaction centers with approximately equal affinity. PMID- 6257287 TI - Structural role of phospholipids in ubiquinol-cytochrome c reductase. AB - The role of phospholipids in ubiquinol-cytochrome c reductase has been studied by the following methods: (1) removal and restoration of phospholipids, (2) circular dichroism measurements, and (3) phospholipase A2 treatment. Over 90% of the phospholipids in the cytochrome b--c1 III complex (a highly purified ubiquinol cytochrome c reductase) can be removed by repeated precipitation with ammonium sulfate in the presence of 0.5% sodium cholate. The delipidated enzyme complex is inactive. Full restoration of enzymatic activity can only be achieved with a freshly prepared delipidated enzyme complex, made in the presence of 20% glycerol. As the age of the delipidated enzyme increased, the amount of activity restored decreased and the incubation time required to reach maximal activity increased. Removal of phospholipids from the cytochrome b--c1 III complex resulted in an immediate decrease of approximately 15% in molar ellipticities in both the far-UV and the Soret regions. A further decrease in ellipticities was observed upon incubation of the delipidated enzyme at 0 degrees C in 50 mM phosphate buffer, pH 7.4. Replenishing phospholipids to the delipidated enzyme complex restored enzymatic activity and the molar ellipticity in both regions. The absolute requirement for phospholipids in the cytochrome b--c1 III complex was also demonstrated by treatment of the enzyme with purified phospholipase A2. The inactivation of the cytochrome b--c1 III complex by phospholipase A2 was not prevented by the presence of excess exogenous ubiquinone but was prevented by the presence of ethylenediaminetetracetic acid (EDTA). The enzymatic activity of the phospholipase A2 treated complex is fully restorable upon the addition of EDTA and phospholipids. PMID- 6257288 TI - Resonance Raman evidence for intramolecular electron transport from flavin to heme in flavocytochrome c-552 and nature of chromophoric interactions. PMID- 6257289 TI - A unique, pepsin-sensitive collagen synthesized by aortic endothelial cells in culture. AB - A unique collagen, designated EC, has been isolated from the culture medium of adult bovine aortic endothelial cells. After diethylaminoethylcellulose chromatography of [3H]proline-labeled culture medium, three non-disulfide-bonded bacterial collagenase-sensitive components with apparent Mr of 177000 (EC 1), 125000 (EC 2), and 100000 (EC 3) were demonstrated. Molecular sieve chromatography, cyanogen bromide cleavage, and two-dimensional peptide mapping of radioiodinated EC fragments produced by protease digestion suggest that the lower molecular weight components originate from EC 1. Both EC 1 and EC 2 were digested by pepsin within 10 min to products of less than 60000 molecular weight, under conditions which supported only limited proteolysis of other native collagens. A pepsin-resistant fragment of Mr 50000, derived from a digest of EC 2, contained equal amounts of hydroxyproline and proline, suggesting that at least a portion of the endothelial collagen contains a stable, collagen-like triple helix. Comparative mapping using mast cell protease and cyanogen bromide cleavage, followed by polyacrylamide gel electrophoresis, indicates that the primary structure of this collagen differs from that of other known collagen types. PMID- 6257290 TI - Phosphorylase phosphatase complex from skeletal muscle. Activation of one of two catalytic subunits by manganese ions. AB - Sarcoplasmic phosphorylase phosphatase extracted from ground skeletal muscle was recovered in a high molecular weight from (Mr = 250000). This enzyme has been purified from extracts by anion-exchange and gel chromatography to yield a preparation with three major protein components of Mr 83000, 72000, and 32000 by sodium dodecyl sulfate gel electrophoresis. The phosphorylase phosphatase activity of the complex form was activated more than 10-fold by Mn2+, with a K0.5 of 10(-5) M, but not by Mg2+ or Ca2+. Manganese activation occurred over a period of several minutes and resulted primarily in an increase in Vmax of a phosphatase that was sensitive to trypsin. Activation persisted after gel filtration, and the active form of the enzyme did not contain bound manganese measured by using 54Mn2+. A contaminating p-nitrophenylphosphatase was activated by either Mn2+ (K0.5 of 10(-4) M) or Mg2+ (K0.5 of 10(-3) M). Unlike the protein phosphatase this enzyme was inactive following removal of the metal ions by gel filtration. The phosphatase complex could be dissociated into its component subunits by precipitation with 50% acetone at 20 degrees C in the presence of an inert divalent cation, reducing agent, and bovine serum albumin. Two catalytic subunits were quantitatively recovered; one of Mr 83000 was a trypsin-sensitive manganese activated phosphatase and the second of Mr 32000 was trypsin-stable and metal ion dependent. Both enzymes were effective in catalyzing the dephosphorylation of either phosphorylase a or the regulatory subunit of adenosine cyclic 3',5' phosphate (cAMP) dependent protein kinase, but neither subunit possessed p nitrophenylphosphatase activity. PMID- 6257292 TI - Pyruvate phosphate dikinase: sequence of the histidyl peptide, the pyrophosphoryl and phosphoryl carrier. AB - Pyruvate phosphate dikinase contains a pivotal histidyl residue which functions to mediate the transfer of phosphoryl moieties during the reaction catalyzed by the enzyme. The tryptic peptide which contains this essential histidyl residue has been isolated by a two-step procedure originally developed by Wang and co workers [Wang, T., Jurasek, L., & Bridger, W. A. (1972) Biochemistry 11, 2067]. This peptide has been sequenced by the manual dansyl-Edman procedure and is shown to be NH2-Gly-Gly-Met-Thr-Ser-His-Ala-Ala-Val-Val-Ala-Arg-CO2H. There is no readily interpretable homology between this peptide and other phosphorylated histidyl peptides previously isolated from other enzymes. By use of Chou & Fasman [Chou, P. Y., & Fasman, G. D. (1974) Biochemistry 13, 222], it is predicted that the sequence contains an alpha helix from the methionine residue through to the carboxyl terminal arginine residue. PMID- 6257291 TI - Formation of porphyrin pi cation radical in zinc-substituted horseradish peroxidase. AB - Zinc-substituted horseradish peroxidase is oxidized by K2IrCl6 to a characteristic state which retains one oxidizing equivalent more than the zinc peroxidase. The oxidized enzyme gives an optical absorption spectrum similar to that of compound I of peroxidase and catalase, and a g = 2 electron paramagnetic resonance signal which has an intensity corresponding to the porphyrin content. It is reduced back to the zinc peroxidase by a stoichiometric amount of ferrocyanide or by a large excess of K3IrCl6. From the equilibrium data, the value of E0' for the zinc peroxidase couple is estimated to be 0.74 V at pH 6. The oxidized zinc peroxidase is also formed by the addition of H2O2 or upon illumination with white light. The rate constants for the oxidation by K2IrCl6 and H2O2 at pH 8.0 are 8 x 10(5) and 8 x 10(2) M-1 s-1, respectively. No essential spectral change can be observed when K2IrCl6 is added to the metal-free peroxidase (protoporphyrin--apoperoxidase complex) or to zinc-substituted sperm whale myoglobin. PMID- 6257293 TI - Pyruvate phosphate dikinase: affinity labeling of the adenosine 5'-triphosphate- adenosine 5'-monophosphate site. PMID- 6257294 TI - Single-stranded poly(deoxyguanylic acid) associates into double- and triple stranded structures. AB - Circular plasmid deoxyribonucleic acid (DNA), pBR322, was digested with the restriction endonuclease PstI to give full-length double-stranded DNA molecules, terminated by two self-complementary single-stranded sequences: (formula: see text). The protruding 3' termini were extended with dG by using calf thymus terminal deoxynucleotidyl transferase and dGTP, to form single-stranded tails of oligo(dG). At a length of about dG15, such tails become resistant to single strand specific endonuclease S1, and also cease to function as substrate (initiator) for the terminal deoxynucleotidyl transferase. This altered reactivity arises from association of the oligo(dG) tails into double- and triple stranded structures, resulting in linear, circular, and branched polymers of the monomeric linear plasmid DNA. All these polymeric structures of the plasmid DNA are stable at room temperature, can be observed in the electron microscope, and can be separated from each other by agarose gel electrophoresis. At 60 degrees C or in 50% formamide, most of the oligo(dG) self-association can be reversed (melted), and the plasmid DNA is again found as the original linear monomer. PMID- 6257295 TI - Proton nuclear magnetic resonance and electron paramagnetic resonance studies on skeletal muscle actin indicate that the metal and nucleotide binding sites are separate. AB - The distance separating the high-affinity binding sites of actin for a divalent metal ion and nucleotide was evaluated by using high-resolution proton NMR and EPR spectroscopy. Replacement of the Ca2+ or Mg2+ bound to the high-affinity divalent cation site of G-actin by trivalent lanthanide ions such as La3+, EU3+, or Gd3+ results in an increase in the mobility of the bound ATP as observed in the NMR spectra of G-actin monomers. Little difference was observed between the spectra obtained in the presence of the diamagnetic La3+ control and the paramagnetic ions Eu3+ and Gd3+ which respectively shift and broaden the proton resonances of amino acids in the vicinity of the binding site. Analysis of the NMR spectra indicates that the metal and nucleotide binding sites are separated by a distance of at least 16 A. In the past, the metal and ATP have been widely assumed to bind as a complex. Further verification that the two sites on actin are physically separated was obtained by using an ATP analogue with a nitroxide spin-label bound at the 6' position of the purine ring. An estimate of the distance was made between the site containing the ATP analogue and the paramagnetic ion, Mn2+, bound to the cation binding site. These EPR experiments were not affected by the state of polymerization of the actin. The data obtained by using this technique support the conclusion stated above, namely, that the cation and nucleotide sites on either G- or F-actin are well separated. PMID- 6257297 TI - Transverse motion of chlorophyll derivatives in phospholipid bilayers. AB - Chlorophyll derivatives were synthesized with spin labels attached to the porphyrin ring. These labels were incorporated into egg phosphatidylcholine vesicles in order to estimate the transbilayer motion (flip-flop) of this class of photosynthetic pigments. Using the ascorbate reduction method, the upper limit to the spin label half-life is tau 1/2 approximately 4 min at 0 degrees C. The flip-flop rate is rapid compared to that of a phospholipid spin label under the same conditions. The presence or absence of magnesium in the center of the porphyrin ring had no measurable effect on the flip-flop rate. PMID- 6257296 TI - On the fidelity of deoxyribonucleic acid synthesis directed by chromatin associated deoxyribonucleic acid polymerase beta. AB - Accuracy of poly[d(A-T)] synthesis catalyzed by chromatin-bound deoxyribonucleic acid (DNA) polymerase beta was measured with several types. A new procedure was developed for the isolation of copied poly[d(A-T)] from chromatin DNA. This method involved in vitro copying of poly[d(A-T)] by native chromatin and subsequent selective fragmentation of chromatin by restriction nucleases, proteinase K, and heat denaturation. The fragmented natural DNA is then separated from the high molecular weight poly[d(A-T)] by gel filtration. The efficacy of DNA removal by this procedure was validated by cesium chloride gradient and nearest-neighbor analysis of the product of the reaction and by measurement of the fidelity of poly[d(A-T)] synthesis by Escherichia coli DNA Pol I contaminated with increasing amounts of DNA. Also, DNA polymerases dissociated from chromatin retain the same accuracy as that of native chromatin. Synthesis of poly[d(A-T)] by chromatin is catalyzed mainly by DNA polymerase-beta. By use of the described technique, we find that the fidelity of this reaction is exceptionally low; approximately one dGTP was incorporated for every thousand complementary nucleotides polymerized. PMID- 6257298 TI - Block of sodium conductance by n-octanol in crayfish giant axons. AB - The block of the Na+ current by n-octanol was studied in crayfish giant axons under axial wire voltage-clamp conditions. Standard kinetic analysis of the Na+ currents was undertaken to test the hypothesis tha the n-octanol-induced block of the Na+ current could be accounted for on the basis of changes in the voltage dependence of the kinetic parameters. Alterations in the membrane dipolar potential arising from rearrangement of membrane lipids would be the anticipated source of changes in the voltage dependence. Although some changes in voltage dependence did evolve with the block by n-octanol, the changes were not of sufficient magnitude to account for the block. In conclusion, although higher concentrations of n-octanol produced shifts along the voltage axis of the kinetic parameters, direct blocking action of n-octanol on the channel appears to be the most important mechanism of the block. PMID- 6257300 TI - Action of ortho- and paramyxovirus neuraminidase on gangliosides. Hydrolysis of ganglioside GM1 by Sendai virus neuraminidase. AB - The action of neuraminidase of influenza A virus, Sendai virus and Newcastle disease virus particles on bovine brain ganglioside GM1 and the properties of Sendai virus neuraminidase for GM1 were studied. With Sendai virus, GM1 was hydrolyzed to asialo-GM1 (GA1) and N-acetylneuraminic acid even in the absence of surfactant or other additives, while the hydrolysis of GM1 by Newcastle disease virus or influenza A virus was very low or undetectable under the same conditions. The formation of GA1 by Sendai virus neuraminidase was confirmed by thin-layer chromatography and immunodiffusion test using anti-GA1 antiserum. The apparent Km of Sendai virus neuraminidase for GM1 hydrolysis was found to be 2.67 x 10(-4) M and the optimum pH was 5.6. GM3, GM2 and oligosaccharide of GM1 were hydrolyzed more effectively than GM1 in the absence of surfactant (GM3 greater than GM2 greater than oligosaccharide of GM1 greater than GM1). The hydrolysis of GM1 by the Sendai virus enzyme was stimulated by the addition of sodium cholate or sodium taurocholate, but was inhibited by divalent cations (10 mM), Ca2+, Mg2+, ZN2+, Fe2+ and CU2+. In the absence of the surfactant, Sendai virus neuraminidase hydrolyzed GM1 more efficiently than Arthobacter ureafaciens neuraminidase which has been reported recently as being an adequate enzyme to hydrolyze ganglioside GM1 as a substrate. PMID- 6257299 TI - Factors controlling the metabolism of phosphatidate by phosphohydrolase and phospholipase A-type activities. Effects of magnesium, calcium and amphiphilic cationic drugs. AB - 1. The simultaneous deacylation and dephosphorylation of 1,2-diacyl-sn [3H]glycerol 3-phosphate by the microsomal and soluble fraction of rat liver was studied. The substrate was either in the form of an emulsion or bound to microsomal membranes. 2. Mg2+ stimulated the deacylation and dephosphorylation of phosphatidate emulsions by both fractions, although the stimulation of both microsomal activities was less than that in the soluble fraction. The preparations of membrane-bound phosphatidate contained Mg2+. Further addition of Mg2+ inhibited dephosphorylation, whereas low concentrations of EDTA stimulated. Additional Mg2+ had little effect on the deacylation of membrane-bound phosphatidate and EDTA inhibited it. 3. Ca2+ inhibited the phosphohydrolase reactions in both fractions, but had little effect on the deacylation of phosphatidate emulsions or membrane-bound phosphatidate. 4. In the absence of Mg2+, lower concentrations of amphiphilic cations (chlorpromazine and benfluorex) stimulated the deacylation and dephosphorylation of phosphatidate emulsions by the soluble fraction. They also stimulated deacylation by the microsomal fraction, but inhibited dephosphorylation. In the present of 5 mM MgCl2, these drugs inhibited the dephosphorylation and deacylation of phosphatidate emulsions, the deacylation reaction being slightly less sensitive. Chlorpromazine (0.4 and 0.8 mM) also inhibited the dephosphorylation of membrane-bound Mg2+-phosphatidate by microsomal and microsomal plus soluble fractions. The deacylation was stimulated by 0.4 mM chlorpromazine and by 1 and 2 mM norfenfluramine. Chlorpromazine (0.8 mM) inhibited the deacylation by microsomal plus soluble fractions, but not by microsomal fractions alone. 5. The possible importance of the deacylation of phosphatidate in the physiological and pharmacological control of glycerolipid synthesis is discussed. PMID- 6257301 TI - The stimulation of rat liver microsomal CTP: phosphatidate cytidylyltransferase activity by guanosine triphosphate. AB - GTP has been found to markedly enhance the formation of CDPdiacylglycerol in rat liver microsomes. The magnitude of the GTP stimulatory effect was influenced by the fatty acid composition of the phosphatidic acid substrate. Heat or proteolytic treatment of microsomal membranes prevented GTP from stimulating liponucleotide formation. Treatment of microsomes with low levels of detergent reduced the stimulatory action of the GTP. The increased synthesis of CDPdiacylglycerol obtained by the addition of GTP to the incubation medium is due to an increase in CTP:phosphatidate cytidylyltransferase activity, rather than to a reduction in the breakdown of either the substrates or product of the reaction. The results suggest that some other protein or enzyme mediates the effect of GTP upon CTP:phosphatidate cytidylyltransferase activity. PMID- 6257303 TI - 1H-NMR studies of the coordination geometry at the heme iron and the electronic structure of the heme group in cytochrome c-552 from Euglena gracilis. AB - The 1H-NMR lines of heme c in reduced and oxidized cytochrome c-552 from Euglena gracilis were individually assigned and the coordination geometry of the axial ligands was investigated. The electronic structure of the heme and the chirality of the axially bound methionine were found to be of the same type as in mammalian cytochrome c, but different from cytochrome c-551 from Pseudomonas aeruginosa. These results provide additional support for a previously proposed correlation between the chirality of attachment of the axial methionine and the electronic wave functions in oxidized cytochromes of the c type. Comparison of mammalian cytochrome c, cytochrome c-551 and cytochrome c-552 indicates that the chirality of the axially bound methionine is not linked with the evolutionary increase of the polypeptide chain length. PMID- 6257302 TI - A lysosomal storage disorder in mice characterized by a dual deficiency of sphingomyelinase and glucocerebrosidase. AB - Lipid and lysosomal enzyme levels in the tissues of a strain of mice afflicted with an autosomal rescessive neuroviscereal storage disorder were examined. Sphingomyelinase and glucocerebrosidase activities were consistently diminished in a wide variety of tissues obtained from the affected mice. The activities of these enzymes were clearly attenuated in new-born mice, which at this age, were otherwise indistinguishable from littermates and age-matched controls. The deficiency of sphingomyelinase was more pronounced than glucocerebrosidase. There was progressive accumulation of sphingomyelin, glucocerebroside, lactosylceramide and unesterified cholesterol in the tissues of these mice in the postnatal period. Gangliosides GM2 and GM3 accumulated in the brain of the animals, and GM3 and asialo-GM2 were stored in the liver. Furthermore, there was a large increase in the quantity of hepatic bis(monoacylglycero)phosphate. The accumulation of lipids was parallelled by a progressive elevation in the activity of several lysosomal hydrolases in various tissues. Heterozygous mice were biochemically indistinguishable from normal controls. The phenotypic manifestations in these metabolically mutated animals are compared with those in Niemann-Pick disease and Gaucher's disease in humans. PMID- 6257304 TI - Resonance Raman spectra of Pseudomonas cytochrome c peroxidase. AB - Resonance Raman spectra of ferric, ferrous and ferrous-carbonyl forms of Pseudomonas cytochrome c peroxidase are presented. The porphyrin ring vibration frequencies are compared with those of other heme proteins which are in well defined spin and oxidation states. Both the native oxidized and the reduced forms of the enzyme show two sets of Raman lines, one having a low-spin and the other a high-spin character. Resolved bands can be assigned to heme c and heme c', the low-spin and the high-spin moiety of the enzyme, respectively. The low-spin heme moiety of the ferric enzyme is concluded to have an imidazole-nitrogen : heme iron : methionine-sulphur hemochrome structure, whereas in the ferrous enzyme the methionine-sulphur ligation is exchanged with the nitrogen of histidine or lysine (N epsilon). The Raman spectra indicate that the high-spin ferric heme consists of a mixture of a five-coordinated form and a six-coordinated form with a carboxylate group as a ligand. In the reduced enzyme the high-spin heme is five coordinated. The Raman spectrum of the carbonyl derivative of Pseudomonas cytochrome c peroxidase indicates that the compound has an electron structure similar to that of carboxyhemoglobin and carboxymyoglobin. The data confirm earlier results that the two heme moieties of the enzyme are bound to the apoprotein by covalent thioether bonds as in c-type cytochromes. PMID- 6257305 TI - Solubilization of the pig ileal intrinsic factor receptor with papain treatment and studies on the solubilized receptor. AB - The intrinsic factor receptor, known to consist of two subunits alpha and beta, has been solubilized by papain digestion from porcine small intestine. Papain liberates a part of the outermost subunit (alpha) of the receptor. The solubilized part was called papain-alpha. It was purified by affinity chromatography on Sepharose-vitamin B-12-intrinsic factor gel and its molecular dimensions were measured. Its molecular weight measured with SDS-polyacrylamide gel electrophoresis is 45000, its isoelectric point is 4.2 and it binds the cobalamin-intrinsic factor complex in the same way as the whole receptor. PMID- 6257306 TI - Effect of dysprosium on the spin-lattice relaxation time of cytochrome c and cytochrome a. AB - The progressive power saturation of the electron paramagnetic resonance of horse heart cytochrome c and solubilized bovine heart cytochrome oxidase has been monitored at low temperature in the presence of the relaxing agent, dysprosium. The saturation of the EPR signal of cytochrome c is relieved even at 6 K. With increasing temperature the effect is enhanced as the relaxation time of the dysprosium becomes shorter; however, the intrinsic spin-lattice relaxation time, T1, for cytochrome c decreases even more rapidly with increasing temperature. T1 for cytochrome c can be described by an intrinsic component, a component which is proportional to the concentration of dysprosium and a third component due to local binding which is independent of dysprosium concentration. The cytochrome a component of cytochrome oxidase is also affected by dysprosium. In the presence of cytochrome oxidase, T1 for cytochrome c is almost unaffected by dysprosium, indicating that access to the cytochrome c heme is blocked by the binding of c to oxidase. Based on the concentration-dependent effect of dysprosium on the lifetime of cytochrome c, it is possible to make distance estimates from the EPR active center to Dy3+. Dysprosium is therefore useful for determining the spatial relationships among paramagnetic enzyme components in a quantitative way. PMID- 6257307 TI - A 19F nuclear magnetic resonance study of the interaction between cytochrome c and cytochrome c peroxidase. AB - The reaction between ferrocytochrome c and yeast cytochrome c peroxidase was studied using cytochrome c derivatives specifically trifluoroacetylated at single lysine amino groups. The only modifications that decreased the reaction rate were those of lysines immediately surrounding the heme crevice, lysines 13, 25, 79, and 87. Modification of lysines 22, 55, 88, and 99 had no effect on the reaction. The 19F chemical shifts of the cytochrome c derivatives trifluoroacetylated at lysines 13, 79, and 87 were not changed upon complex formation with cytochrome c peroxidase, indicating that no detectable conformational changes occurred. The cytochrome c trifluoroacetyl groups had the same T1 values in the paramagnetic fluorocytochrome c peroxidase complex as in the diamagnetic reduced form of the complex, indicating that they were more than 2.3 nm from the paramagnetic iron atom in cytochrome c peroxidase. This is consistent with a separation of at least 1.5-2.0 nm between the iron atom of cytochrome c and the iron atom of cytochrome c peroxidase. PMID- 6257308 TI - Identification of porphyrin present in apo-cytochrome C oxidase of copper deficient yeast cells. AB - Heme a was not detected either in mitochondria isolated from copper-deficient yeast or in the intact cells. Nevertheless, the intracellular concentration of free porphyrins indicated that the pathway of porphyrin and heme synthesis was not impaired in copper-deficient cells. The immunoprecipitated apo-oxidase from copper-deficient cells revealed an absorption spectrum with maxima at 645, 592, 559, 519 and 423 nm, similar to that of purified porphyrin a. When solubilized mitochondria from [3H]leucine and delta-amino[14C]levulinic acid-labeled copper deficient yeast cells were incubated with rabbit antiserum against cytochrome c oxidase, a precipitate was obtained. Sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis of this immunoprecipitate showed [3H]leucine associated with six bands and delta-amino[14C]levulinic acid resolved in a single band. HCl fractionation of copper-deficient mitochondria labeled with delta amino[14C]levulinic acid showed a high specific radioactivity in the fraction extracted by 20% HCl, a solvent which extracts porphyrin a. Thin-layer chromatography of the radioactivity found in 20% HCl showed an RF value identical to that of purified porphyrin a. When delta-amino[3H]levulinic acid-labeled, copper-deficient yeast cells are grown in copper-supplemented medium, the porphyrin a accumulated in copper-deficient cells was converted into heme a, and this conversion was prevented by cycloheximidine. These observations suggest that porphyrin a is present in the apo-oxidase of copper-deficient cells, but that the conversion to heme a does not occur. This conversion reaction appears to be a point in the biosynthetic pathway of cytochrome c oxidase which is blocked by copper deficiency. PMID- 6257309 TI - The effects of cytochalasin B on testosterone synthesis by interstitial cells of rat testis. AB - The present study examined the effects of cytochalasin B on various steps in the luteinizing hormone (LH)-stimulated increase in testosterone synthesis by collagenase-dispersed interstitial cells of adult rat testis. Cytochalasin B at a concentration range of 0.1--50 microM inhibited the LH-stimulated increase in testosterone synthesis in a dose-dependent manner. Both intracellular and medium (released) testosterone levels were reduced, thus indicating that the decrease was not due to the accumulation of testosterone inside the cell as a result of cytochalasin B treatment. Cytochalasin B also inhibited the 8-bromocyclic AMP and pregnenolone-stimulated testosterone synthesis in a similar dose-dependent manner. Cytochalasin B at the two higher doses (10 and 50 microM) also inhibited the LH-stimulated generation of cyclic AMP by interstitial cells. However, this drug had no effect on basal testosterone synthesis except at the highest concentration added. Previous studies on adrenocorticotropic hormone (ACTH)- and LH-stimulated increase in glucocorticoid and testosterone synthesis in adrenal and Leydig cells, respectively, demonstrated that cytochalasin B or anti-actin inhibited the transport of cholesterol into mitochondria. The present studies suggest that cytochalasin B inhibits at least two additional steps in the LH stimulated increase in testosterone synthesis: (1) the generation of cyclic AMP at the level of the plasma membrane, and (2) the conversion of pregnenolone to testosterone at the level of the smooth endoplasmic reticulum. It remains to be established whether these are direct effects of cytochalasin B, or whether they are mediated by disruption of microfilaments by cytochalasin B. PMID- 6257310 TI - Inhibition of lipolysis and cyclic AMP accumulation by adenosine analogues in hamster epididymal adipocytes exposed to cholera toxin. AB - The effects of adenosine, N6-phenylisopropyl adenosine and 2',5'-dideoxyadenosine on lipolysis and cyclic AMP accumulation, in hamster adipocytes treated with cholera toxin, were studied. Cholera toxin caused an increase in lipolysis and cyclic AMP accumulation that was dependent upon the concentration of toxin and the length of time cells were exposed to the toxin. When N6-phenylisopropyl adenosine or 2',5'-dideoxyadenosine were present, the lipolytic and cyclic AMP responses to cholera toxin were inhibited. The adenosine analogues were equally effective inhibitors of lipolysis and cyclic AMP accumulation, when they were added 1 or 2 h after exposure to the toxin. Enzymatic removal of endogenously produced adenosine with adenosine deaminase potentiated both the lipolytic and cyclic AMP responses to cholera toxin. In addition, the inhibitory effects of N6 phenylisopropyl adenosine, 2'5'-dideoxyadenosine and clonidine on lipolysis and cyclic AMP were enhanced consequent to enzymatic removal of adenosine. These data show responses of intact fat cells to N6-phenylisopropyl adenosine, 2',5' dideoxyadenosine or removal of endogenous adenosine and provide evidence for an adenosine sensitivity of fat cells exposed to cholera toxin. PMID- 6257311 TI - Beta-adrenergic receptor-adenylate cyclase alterations during the postnatal development of skeletal muscle. AB - The postnatal development of mammalian skeletal muscle is associated with an increased capacity for glycogenolysis. In the present study rabbit skeletal muscle underwent a 7-fold increase in glycogen synthase and glycogen phosphorylase activity over the postnatal period of 0--8 weeks. An enriched fraction of sarcolemma was prepared from neonatal and adult muscle to examine the development of the beta-adrenergic receptor-adenylate cyclase system. Adult membranes possessed a 2-fold greater Na+K+(Mg2+)-ATPase activity and a 6--8 fold greater sodium fluoride- and epinephrine-stimulated adenylate cyclase activity. The activation ratio (effector activity/basal activity) increased 2--3 fold for epinephrine and sodium fluoride in adult sarcolemma. The activation by catecholamines conformed to the physiological beta 2 type response with isoproterenol (1.8 . 10(-8) M) > epinephrine (1.1 . 10(-7) M) > norinephrine (3.2 . 10(-6) M). In contrast, binding studies employing (-)-[3H]dihydroalprenolol showed little difference between neonatal and adult membranes with respect to (1) number of binding sites, (2) equilibrium dissociation constant and (3) displacement of (-)-[3H]dihydroalprenolol by catecholamine agonists. Protein and lipid components of the sarcolemma were also modified during development. Neonatal membranes possessed two glycopeptides of Mr 80000 and 86000, whereas in the adult only a single Mr 113000 species was evident. The total lipid phosphorus and phospholipid composition was unchanged during development. The content of linoleic acid increased approx. 3-fold during development in the phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine phospholipids. The cholesterol content of adult membranes was decreased by 29% compared to neonatal membranes. PMID- 6257312 TI - Effects of hippocampal brain damage on auditory and visual recent memory: comparison with marijuana-intoxicated subjects. AB - A battery of tests clinically employed for the estimation of auditory and visual recent memory dysfunction was administered to eight subjects having circumscribed damage to the temporal lobe. It was hypothesized that the performance of subjects with temporal lobe lesions would qualitatively resemble that of subjects intoxicated with marijuana. Where comparisons could be made, the performance of these "temporal lobe" patients paralleled the performance of subjects acutely intoxicated with known doses of delta 9-THC. Results are discussed in terms of cannabinoid actions on hippocampal functioning and, in general, support the hypothesis that the action of marijuana in the brain may focus in the hippocampal region and produce behavioral changes similar to that resulting from traumatic injury or removal of the region. PMID- 6257314 TI - Evaluation of surface markers on normal human lymphocytes containing parallel tubular arrays: a quantitative ultrastructural study. PMID- 6257313 TI - Development of suppressor T lymphocytes for Epstein-Barr virus-induced B lymphocyte outgrowth during acute infectious mononucleosis: assessment by two quantitative systems. AB - A system of 3H-thymidine incorporation by lymphocytes in culture for 3 wk has been utilized for quantitative assessment of the ability of T lymphocytes to inhibit outgrowth of autologous Epstein-Barr virus (EBV) transformed B lymphocytes. Lymphocytes from EBV-seronegative individuals lack the ability to suppress outgrowth of autologous EBV-transformed B lymphocytes. This capability appears during the course of primary EBV-induced infectious mononucleases (IM) as the atypical lymphocytosis is subsiding and persists for years after recovery from primary EBV infection. The ability of T lymphocytes from EBV-seropositive subjects or convalescent IM patients to inhibit B-lymphocyte outgrowth is not HLA restricted. Thus, T lymphocytes capable of inhibition of in vitro EBV-induced B cell outgrowth emerge during the acute stage of IM and may represent an important control mechanism of EBV-induced B-lymphocyte proliferation in vivo. The system provides a highly sensitive quantitative means for in vitro assessment of cell mediated immunity to EBV. PMID- 6257315 TI - Effects of asulam on some microbial activities of three soils. PMID- 6257316 TI - [An investigation using E.P.R. on sample of bovine enamel, from deciduous and permanent teeth, normal and fluoridated teeth, irradiated with x-rays and beta rays]. PMID- 6257317 TI - Herpesviruses and human cancer. PMID- 6257318 TI - The radiology of carcinoma of the ear. AB - Carcinoma arising in external auditory meatus, middle ear cleft or mastoid cavity has a poor prognosis unless treated at an early stage. Biopsy of any suspicious tissue is the key to early diagnosis but there are radiological features which may suggest the presence of a malignant neoplasm. An important role of radiology is the demonstration of the extent of disease and of spread beyond the confines of the temporal bone. The optimum regime of surgery and radiotherapy cannot be planned without this information. The radiological features of 47 aural carcinomas were reviewed. Thirty-two of the cases were examined by multidirectional tomography and six by computed tomography. The modes of spread of the neoplasm are discussed as well as the differential diagnosis. It is concluded that high resolution CT is now the optimum method of demonstrating tumour spread in the axial plane and frequently also in the coronal section. Lateral tomograms are necessary to show erosion of the walls of the external auditory meatus. Erosion of the bony septum separating the middle ear cavity from the carotid canal can be shown on coronal sections and is an important sign of spread anteriorly. Soft tissue extension into the infratemporal fossa may be demonstrated by high resolution CT. PMID- 6257319 TI - Neurotoxicity with desmethylmisonidazole. PMID- 6257320 TI - Idiopathic hypercalciuria: its control with unprocessed bran. AB - Eighty-four patients with idiopathic hypercalciuria were entered into a study of the effects of treatment with unprocessed bran. Of 72 patients with complete data available for analysis 62 (86%) had a significant reduction in urinary calcium excretion during bran treatment and 28 (39%) returned their calcium excretion to within the normal range. Unprocessed bran is therefore an effective means of reducing urinary calcium excretion in patients with idiopathic hypercalciuria. PMID- 6257321 TI - Treatment of insulinomas. PMID- 6257322 TI - Rotavirus infection in an obstetric unit. PMID- 6257323 TI - Bronchial adenomas. PMID- 6257324 TI - Primary liver cell cancer in autoimmune chronic liver disease. PMID- 6257325 TI - Epstein-Barr-virus-carrying lymphoma in a patient with ataxia-telangiectasia. AB - An undifferentiated lymphocytic lymphoma of mesenteric lymph nodes occurred in a young boy with ataxia-telangiectasia. Two independent tests, Epstein-Barr virus (EBV)-cRNA/DNA hybridisation and EBV DNA/DNA reassociation kinetic analysis, showed 53 and 68 EBV genome equivalents per cell respectively, which was compatible with an EBV-genome-carrying tumour. Whether this was a polyclonal lymphoproliferation or a monoclonal tumour could not be determined owing to lack of suitable material. The presence of EBV genomes should be sought in lymphomas arising in ataxia-telangiectasia and other immunodeficiencies. PMID- 6257326 TI - Facilitation of acetylcholine secretion at a mouse neuromuscular junction. AB - Facilitation of transmitter secretion from motor nerve terminals following one or more conditioning stimuli was examined in mouse sternomastoid muscles. Following a single conditioning stimulus at 20 degrees C, facilitation decayed exponentially during the first 70-80 msec with a time constant of 60 msec. After 70--80 msec, a small slower component of facilitation was apparent. Initial facilitation (obtained by extrapolation back to 'zero' time) had a value of approximately 0.5. Following more than one conditioning stimulus (2-6), initial facilitation was greater but the pattern of decay was similar, the slower component becoming more obvious as the number of conditioning stimuli was increased. The slow decay phase also appeared exponential. The pattern of decay of facilitation could be well fitted by the sum of two exponentials, F1 (0)exp(- t/tau 1) + F2(0)exp(--t/tau 2). After a single stimulus at 20 degrees C, tau 1 and tau 2 had mean values of 35 and 163 msec. The main effect of increasing the number of conditioning stimuli was to increase (F1(0) and F2(0) with little change in tau 1 or tau 2. Changing temperature from 30 degrees C to 10 degrees C increased F1(0) and tau 2 but had relatively little effect on F2(0) and tau 1. PMID- 6257327 TI - Effect of naloxone upon diffuse noxious inhibitory controls (DNIC) in the rat. AB - Twenty-eight convergent neurones, responding to both noxious and innocuous stimuli applied to their cutaneous receptive fields were recorded at the lumbar level in anaesthetized intact rats. These cells received Aa and C fibre inputs as shown by electrical stimulation of their receptive fields, and were located in the medial part of the dorsal horn. (a) For 15 units, Diffuse Noxious Inhibitory Controls (DNCI)67,68 were investigated by applying noxious thermal stimuli (52 degrees C) to the distal two-thirds of the tail. This conditioning stimulus induced strong inhibition of the responses to both Aa (28%) and C (71%) fibres. Post-effects of long duration were commonly observed after cessation of the conditioning stimulus. The systemic injection of naloxone (0.3 mg/kg, i.v.) resulted in a partial reduction in these inhibitory effects with a decrease of about 50% for both Aa and C fibre response 10 min after naloxone administration. This was followed by a progressive recovery lasting 30 min. (b) 28 convergent units, including the 15 reported above, were recorded to investigate the effect of naloxone upon the unconditioned response. Responses to Aa fibre were unaffected, whereas the responses to C fibre were slightly (17%) but significantly increased by naloxone. PMID- 6257328 TI - Locus coeruleus modulation of dorsal horn unit responses to cutaneous stimulation. PMID- 6257329 TI - Laser action spectrum of reduced excitability in nerve cells. AB - The change in excitability of unstained nerve cells from neonatal rat cerebellum was measured as a function of the energy flux and wavelength of incident laser light. The energy flux was in the range of 0 to 100 microJ/sq. microns. 6 wavelengths between 490 and 685 nm were used. Laser pulses above a threshold energy flux significantly reduced the cells' excitability as measured by extracellular stimulation. The sensitivity of the cells, defined as the inverse of the threshold energy density, increased by an order of magnitude toward the shorter wavelengths. These results are consistent with primary absorption of the light by mitochondrial enzymes, resulting in local heating followed by mitochondrial calcium release into the cytoplasm. PMID- 6257330 TI - [Diffuse pulmonary adenomatosis. Diagnostic contribution of viscosimetry of the sputum]. PMID- 6257331 TI - Case report: an unusual case of gallbladder cancer in an automotive worker. AB - Mucinous adenocarcinoma of the gallbladder was found at autopsy in a 65-year-old male. The tumor was composed predominantly of signet ring cells, an uncommon histologic form. In addition, there was an atypical pattern of metastasis, with cancer involving not only the walls of the cystic duct, large and small bowels, peritoneum, abdominal nodes, and omentum, but also the kidneys, ureters, lungs, and heart. Although the patient lacked the common predisposing factors for gallbladder cancer, he did work in an industry with a significant relative risk for the development of this cancer. PMID- 6257332 TI - Silicon: a requirement in bone formation independent of vitamin D1. PMID- 6257333 TI - Cytochemical studies on the ferritin-containing vesicles of the rat incisor ameloblasts with special reference to the acid phosphatase activity. AB - Acid phosphatase was localized in rat incisor ameloblasts without prior decalcification. When beta-glycerophosphate was used as the substrate, an intense reaction was observed in the supranuclear region of the secretory ameloblasts. But the reaction was dramatically reduced at the transitional stage and was very weak in the maturation ameloblasts. When p-nitrophenylphosphate was the substrate, the reaction product was consistently seen in the Golgi cisternae and the vesicular components of the ameloblasts at all stages of enamel development. These observations suggest that there are two acid phosphatases in ameloblasts. One is in the secretory ameloblasts and the other in the transition and maturation ameloblasts. X-ray microanalyses for Fe and Pb showed that Fe and acid phosphatase were in the ferritin-containing vesicles at the later stage of enamel maturation. This evidence suggests that ferritin is digested in these vesicles for the release of the Fe pigment to the enamel. An increase in the number of intercellular bridges between ameloblasts was correlated with the dramatic decrease in height of ameloblasts at the pigment release stage. The ameloblast membranes were acid phosphatase positive at the intercellular bridges when p nitrophenylphosphate was the substrate. This activity may be involved in the reduction in the surface area of the ameloblast membranes. PMID- 6257334 TI - 13C enriched carbonate apatites studied by ESR: comparison with human tooth enamel apatites. PMID- 6257335 TI - Adenylate cyclase in lean and obese (ob/ob) mouse epididymal white adipocytes. AB - The results presented in this study indicate that the defect in catecholamine stimulated adenylate-cyclase which is characteristic of the ob/ob mouse is associated with a decrease in the sensitivity of the system to guanine nucleotides (guanosine 5'-[beta gamma-imido]triphosphate and guanosine 5' triphosphate). No difference in the beta-adrenergic receptor activity was found between the lean and obese mice on the basis of their capacity to bind the beta adrenergic antagonist [3H]dihydroalprenolol. The data suggest that a defect in the activation of the adenylate cyclase by beta-adrenergic agents may reside in the guanyl nucleotide binding site(s). PMID- 6257336 TI - Properties of a dolichol phosphokinase activity associated with rat liver microsomes. AB - Rat liver microsomes show a capacity to synthesize [1-3H]dolichyl phosphate from [1-3H]-dolichol. Formation of [1-3H]dolichyl phosphate increased continuously over 15 min although the reaction rate was never completely linear. Product formation was directly proportional to microsomal protein concentration between 1.1 mg/mL and the highest concentration tested, 5.5 mg/mL. The reaction rate was linear with respect to the dolichol content of the assay mixture to a saturation point (120 microM). An apparent Km of 50 microM was established for dolichol. The normal phosphate donor for the reaction is CTP and not ATP. The optimum concentration of CTP was 10 mM, and an apparent Km of 4 mM was calculated for this nucleoside triphosphate. The reaction was totally dependent on divalent metal ion, magnesium being more effective than calcium. The optimum concentration of magnesium ion and CTP were the same (10 mM), suggesting that MgCTP2- is utilized as the normal enzyme substrate. Activity measured in the absence of Triton X-100 was only 5% of the activity observed at the optimum (0.5% w/v) detergent concentration. The measurable levels of dolichol phosphokinase could be doubled by the inclusion of 10-15 mM NaF as phosphatase inhibitor. Optimal enzymatic activity was obtained between pH 7.0 and pH 7.5 and could be inhibited by EDTA. The sulfhydryl reagent DTT was slightly stimulatory while the product of the reaction, dolichyl phosphate, was noninhibitory at the highest concentration tested (13.8 microM). The second reaction product (CDP) inhibits the enzymatic phosphorylation of dolichol. PMID- 6257337 TI - Intracellular (Golgi) receptors for insulinlike peptides in rat liver. AB - An insulinlike peptide (ILAs) has been isolated in our laboratory from human serum. The binding of 123I-labeled ILAs was studied in subcellular fractions from rat liver and found to be much greater in microsomes than purified plasmalemma. The high level of microsomal binding was due to a particular enrichment of binding sites in Golgi elements. Binding to Golgi was time and temperature dependent and was augmented by an increase of either subcellular fraction or 125I labeled ILAs in accordance with a mass action process. Degradation of 125I labeled ILAs was greatest in the Golgi vesicle fraction and was reduced by incubation at 4 degrees C. Bound 125I-labeled ILAs could be eluted and was found to retain integrity. Binding was pH dependent with a broad optimum at pH 7.7-8.5. Dissociation of bound 125I-labeled ILAs was time and temperature dependent. It was greater at 37 than 4 degrees C, and was uninfluenced by unlabeled ILAs. The ILAs receptor was stable at 4 degrees C but was markedly decreased by preincubation at 37 degrees C. The binding of 125I-labeled ILAs was inhibited by unlabeled ILAs and related insulinlike peptides (the insulinlike growth factors, IGF-1 and IGF-2) in a dose-dependent manner. Insulin and its analogues had only a partially inhibitory effect, and structurally unrelated peptides were without inhibitory efficacy. In contrast ILAs and IGF-1 and IGF-2 inhibited 125I-labeled insulin binding to its receptors in a dose-dependent fashion. These observations identify a receptor for insulinlike peptides in the Golgi elements of rat liver. It is distinct from the insulin receptor previously observed in these elements. The dual interaction of ILAs and other insulinlike peptides with both the insulin receptor and their own unique receptor constitutes the presumed biochemical basis for the two types of action effected by this family of peptides, namely, an effect on metabolism comparable to insulin and an effect on cellular anabolism and growth. PMID- 6257338 TI - Mitochondrial importation of lipids and liponucleotides from microsomes independent of and facilitated by purified cytosol proteins. AB - The mitochondrial importation of microsomal lipids and liponucleotides in the presence and in the absence of partially purified cytosol protein(s) isolated from guinea pig liver was studied by the aid of isomeric (5-, 12-, and 16-(N-oxyl 4',4'-dimethyloxazolidine)stearoyl) spin-labelled radioactive phosphatide acid, phosphatidylcholine, neutral lipids, and CDP-diglycerides. Using a conventional procedure for the protein purification, cytosol protein(s) was purified approximately 1000-fold in respect to its ability to catalyze the translocation of isomeric spin-labelled lipids and liponucleotides from the microsomal to mitochondrial membranes. The highest activity of this protein was exhibited with biosynthesized spin-labelled lipids and liponucleotides bound to the microsomal membranes as substrates and the lowest, with the synthetic liponucleotides and derived lipids bound to the microsomal membranes. The partially purified protein was active in catalyzing the mitochondrial import of phospholipids from microsomes after heat treatment up to 90 degrees C. In addition to the cytosol protein catalyzing mechanism of mitochondrial import of lipids and liponucleotides from microsomal membranes, another cytosol protein independent mechanism of the mitochondrial importation of the same lipids and liponucleotides was also demonstrated in an agreement with our previous reports on the existence of cytosol protein independent intermembranous translocation of phospholipids. These experimental findings are discussed in terms of possible physiological significance and reaction mechanisms involved in the mitochondrial import of lipids and liponucleotides from the microsomal membranes of guinea pig liver. PMID- 6257339 TI - The influence of chronic ethanol feeding to rats on liver mitochondrial membrane structure and function. AB - Arrhenius plots were generated on the activity of rat liver mitochondrial cytochrome c oxidase from Metrecal-sucrose fed controls and Metrecal-alcohol fed experimentals. Chronic alcohol feeding resulted in diminished specific activity of cytochrome c oxidase and abolition of the discontinuity temperature at 17.5 degrees C found in the controls. Twenty-four hours after alcohol withdrawal, a discontinuity temperature reappeared at 14.4 degrees C; at 48 h it increased to 22.6 degrees C and returned to normal (17.4 degrees C) at 72 h. Such liver mitochondria also showed a decreased capacity to oxidize the acetyl group of acetyl carnitine immediately following prolonged alcohol feeding. When the assay was performed following withdrawal from alcohol 24 h later, oxidation was enhanced and this effect persisted for another 48 h. These latter results revealed a diminished capacity of such mitochondria to oxidize short chain fatty acids during alcohol feeding and the reverse during alcohol withdrawal. These results, complemented by thermographic data obtained through differential scanning calorimetry (DSC) reinforced the view that chronic alcoholic feeding induced adaptive changes in the fluidity of rat liver mitochondrial membrane lipids. Moreover, they demonstrated that in the microenvironment of the membrane bound enzymes on withdrawal from ethanol, the membrane readapts to the new conditions without alcohol. This involved modulation of membrane structure and function and at the same time demonstrated a role for the membrane in the expression of tolerance and functional dependence on alcohol. PMID- 6257340 TI - Headgroup oligosaccharide dynamics of a transmembrane glycoprotein. AB - Glycophorin, a major integral membrane glycoprotein of the human erythrocyte, has been spin labelled on oligosaccharide chains. Electron paramagnetic resonance studies of this glycoprotein in systems of controlled complexity have provided a degree of insight into its headgroup behaviour. (i) When glycophorin is free in solution its oligosaccharide chains exhibit uniformly high freedom of motion. This motional freedom is not attributable to the presence of N-acetyl-neuraminic acid residues. (ii) No evidence has been found of a finite tendency for headgroup sugars to associate with hydrophobic regions of phospholipid or glycoprotein. (iii) Headgroup oligosaccharide dynamics are essentially independent of the state of and interactions of the polypeptide hydrophobic portion (that portion which traverses the membrane). (iv) Nonspecific interaction with proteins and polysaccharides can readily reduce oligosaccharide chain mobility by some 25%, but does not alter their basic behaviour. (v) Binding of wheat germ agglutinin, dramatically immobilizes (terminal) N-acetylneuraminic acid residues. (vi) The above observations hold over the temperature range 0-40 degrees C. (vii) Headgroup carbohydrate mobility is at a minimum in the region of headgroup neutrality (pH 2.6-3.5) and is pH invariant over several pH units in the physiological range. PMID- 6257341 TI - Activation of ouabain-sensitive p-nitrophenylphosphatase by carbachol and cGMP in rat submandibular gland. AB - Na+,K+-ATPase activity was monitored by measuring ouabain-sensitive K+-dependent p-nitrophenylphosphatase (p-NPPase) activity in rat submandibular gland slices. Carbachol (carbamylcholine chloride) stimulated the p-NPPase activity in the presence of calcium but not in its absence. Carbachol activation of the enzyme was totally ouabain sensitive and could be blocked by atropine. A minimal requirement of sodium ion extracellularly was required for this carbachol stimulation. cGMP and its dibutyryl analogue was also effective in stimulating the enzyme activity, whereas, cAMP was ineffective. Calcium, however, was not required for cGMP activation of the p-NPPase activity. The result indicates that calcium is the second messenger and cGMP is the tertiary connection between cholinergic stimulation and Na+,K+-ATPase activation in these glands. Activation of Na+,K+-ATPase is postulated to be responsible for primary fluid formation. PMID- 6257342 TI - Partial purification of diphosphatidylglycerol synthetase from liver mitochondrial membranes. AB - The enzyme responsible for the conversion of phosphatidylglycerol to diphosphatidylglycerol (cardiolipin) in the presence of cytidine diphosphate diacylglycerol is firmly associated with mitochondrial membranes and is not extracted with hypotonic or hypertonic media or with nonionic detergents. Some solubilization was obtained with bile salt solutions, but the zwitter-ionic detergent. Miranol H2M, was most effective in extracting the enzyme. The Miranol extracts were fractionated by column chromatography on Bio-Gel A-1.5 m. The solubilized enzyme is considerably more active in converting unsaturated than saturated phosphatidyl-glycerols, but shows little preference for the cytidine diphosphate diacylglycerols with different fatty acyl substituents. There is an absolute dependence upon divalent cations with the order of effectiveness: Co2+ much greater than Mn2+ greater than Mg2+. In the presence of optimal levels of Co2+ other divalent cations are inhibitory with the order of inhibition: Cd2+ greater than Zn2+ greater than Ca2+ greater than Ba2+ greater than Cu2+ greater than Hg2+ greater than Ni2+. The solubilized enzyme exhibited no requirement for added phospholipids and several phospholipids inhibited the reaction in the order: diphosphatidylglycerol greater than phosphatidylethanolamine greater than phosphatidylserine greater than phosphatidylinositol. PMID- 6257343 TI - Membrane alterations in acute myocardial ischemia. AB - The molecular consequences of acute myocardial ischemia induced in rabbit hearts by ligation of the left circumflex branch of the coronary artery were assessed in terms of the biochemical properties of subcellular organelles. Mitochondrial alteration, as reflected in progressive decrease in the activity of azide sensitive ATPase, was apparent as early as 5 min postligation, but the activity of another mitochondrial enzyme, cytochrome c oxidase, was unchanged, even following 60 min of coronary ligation. Sarcolemmal Na+K+-ATPase exhibited a time course of inactivation similar to that of the mitochondrial ATPase, but differed from the latter in that the impairment was not reversed on reperfusion. Cellular levels of ATP, which decreased in parallel with the loss of ATPase activities, also remained depressed following reperfusion. Decreases in lysosomal enzyme latency were noted, but these occurred somewhat later than the sarcolemmal and mitochondrial alterations. Attempts to demonstrate the production of a population of labile lysosomal structures during ischemia were unsuccessful. Similarly, no alterations in the gel electrophoretic profiles of proteins or in the P phosphatidylcholine/P phosphatidylethanolamine ratio of isolated mitochondrial or sarcolemmal membranes from hearts subjected to ischemia and (or) subsequent reperfusion could be found. It is suggested that sarcolemmal Na+,K+-ATPase may serve as a sensitive and readily quantifiable index of irreversible cellular necrosis and, therefore, be of value in assessing the possible beneficial effects of pharmacological interventions. PMID- 6257344 TI - pH-induced alterations in the structure and activity of cytochrome c oxidase. AB - The effects of pH on the activity and structure of beef heart cytochrome c oxidase have been studied in the pH range 5.0-7.6. (i) A group with pK of approximately 5.45 has been readily detected in the pH vs. activity curve. This group must be deprotonated to achieve maximal activity. (ii) A group with a similar pK (5.45) has been detected and contributes to the spectral character of the reduced oxidase. Over the range pH 5.0-7.6 no other acid-sensitive group contributes to the spectrum of the reduced oxidase. (iii) The oxidized oxidase shows at least three acid-sensitive groups contributing to the spectrum. One occurs in the pH 7 range and another in the pH 5.6 range; below pH 5.2 additional pH-sensitive groups are apparent. Accurate estimation of the pK's of the groups responsible for the spectral changes in the oxidized oxidase has not been possible. (iv) The spectrum of the "oxygenated" (428 nm) conformer of the oxidized protein is invariant over the range ph 5.5-7. (v) The changes occurring in the spectrum of the purified oxidase also occur in the protein contained in phospholipid vesicles. (vi) The data are discussed in terms of the mechanism by which the oxidase, during its in situ catalytic cycle, may give rise to the primary events in energy coupling. PMID- 6257345 TI - The stimulation of rat liver microsomal CDP-diacylglycerol formation by guanosine triphosphate. AB - GTP has been found to markedly enhance the formation of CDP-diacylglycerol in rat liver microsomes. Neither GDP, GMP nor the nonhydrolyzable analogues of GTP increased the synthesis of the liponucleotide. The GTP stimulation of phosphatidate cytidylyltransferase activity is inhibited by EDTA and NaF. GTP enhances the activity of the enzyme in a concentration-, time-, and temperature dependent manner and preincubation of rat liver microsomes with GTP produces a persistently activated phosphatidate cytidylyltransferase. GTP reduces the Km for phosphatidic acid, but has no effect on either the Km for CTP or the Vmax of the reaction. GTP, by stimulating the activity of the phosphatidate cytidylyltransferase, enhances the formation of phosphatidylinositol from CTP, phosphatidic acid, and inositol. Evidence is presented suggesting that the mechanism by which GTP stimulates the activity of the phosphatidate cytidylyltransferase involves a covalent modification of the enzyme itself or a protein intimately associated with the phosphatidate cytidylyltransferase. PMID- 6257346 TI - Friend erythroleukemia cell membrane transferrin receptors. AB - We have compared the uptake of transferrin by murine Friend erythroleukemia cells with the uptake of transferrin by murine reticulocytes. Friend cells which had been induced to erythroid differentiation by dimethyl sulfoxide took up transferrin in a manner qualitatively and quantitatively similar to the uptake of transferrin by reticulocytes, while uninduced Friend cells took up only negligible amounts of transferrin. Specific transferrin-binding activity could be demonstrated in detergent extracts of membranes from induced cells and this activity was isolated from membrane extracts by the use of antibody to transferrin. The isolated membrane component(s) with transferrin-binding activity migrated electrophoretically as a single protein on sodium dodecyl sulfate gels and had similar properties to a transferrin-binding protein isolated previously from reticulocytes. PMID- 6257347 TI - Pathways of cytochrome c oxidation by soluble and membrane-bound cytochrome aa3. AB - In media of low ionic strength, membraneous cytochrome c oxidase, isolated cytochrome c oxidase, and proteoliposomal cytochrome c oxidase each bind cytochrome c at two sites, one of low affinity (1 microM greater than Kd' greater than 0.2 microM) and readily reversible and the other of high affinity (0.01 microM greater than Kd) and weakly reversible. When cytochrome c occupies both sites, including the low affinity site, the maximal turnover measured polarographically with ascorbate and N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD) is independent of TMPD concentration, and lies between 250 and 400 s-1 (30 degrees C, pH 7.4) for fully activated systems. The apparent affinity of the enzyme for cytochrome c is, however, TMPD dependent. When cytochrome c occupies only the high-affinity site, the maximal turnover is closely dependent upon the concentration of TMPD, which, unlike ascorbate, can reduce bound cytochrome c. As TMPD concentration is increased, the maximal turnover approaches that seen when both sites as occupied. The lower activity of isolated cytochrome aa3 is due to the presence of inactive or inaccessible enzyme molecules. Incorporation of isolated enzyme into phospholipid vesicles restores full activity to all the subsequently accessible cytochrome aa3 molecules. Negatively charged (asolectin) vesicles show a higher cytochrome c affinity at the low-affinity sites than do the other enzyme preparations. A model for the cytochrome c-cytochrome aa3 complexes is put forward in which both sites, when occupied, are fully catalytically competent, but in which occupation of the "tight" site by a catalytically functional cytochrome c molecule is required for overall oxidation of cytochrome c via the "loose" site. PMID- 6257348 TI - Nitroxide spin-probe study of amphotericin B-ergosterol interaction in egg phosphatidylcholine multilayers. AB - The interaction between the polyene macrolide antibiotic, amphotericin B, and ergosterol in egg phosphatidylcholine multilayers was investigated using head group and acyl chain nitroxide spin-labelled phosphatidylcholine as probes. At physiological concentrations of less than 15 mol% sterol in egg phosphatidylcholine multilayers amphotericin B accumulates near the head group region until an amphotericin B : ergosterol ratio of approximately 0.7 is achieved. As the proportion of amphotericin B is increased above this value, formation of an acyl chain disordering complex occurs which has an approximate antibiotic:sterol ratio of unity. Dicetyl phosphate was used to increase the solubility of ergosterol past its normal limit in pure egg phosphatidylcholine (approximately 15 mol%). At concentrations of ergosterol higher than 15 mol% a complex of two ergosterol molecules and one amphotericin B was postulated when there was insufficient antibiotic to form a 1:1 complex. PMID- 6257349 TI - Multiple binding sites for local anesthetics in membranes: characterization of the sites and their equilibria by deuterium NMR of specifically deuterated procaine and tetracaine. AB - Anesthetics bound to model membranes were observed directly by means of deuterium nuclear magnetic resonance (NMR). The specifically deuterated local anesthetics procaine and tetracaine were synthesized, and their partition coefficients (water:phosphatidylcholine) and pKa values determined. The interaction of these anesthetics with lamellar dispersions of egg phosphatidylcholine was studied by 2H nuclear magnetic resonance and by electron spin resonance (ESR) of a spin labelled phospholipid at low (5.5) and high (9.5) pH. The ESR experiments suggest that tetracaine intercalates in the membrane and that it equilibrates between water and the phospholipid bilayers of the multilamellar system. The NMR results are consistent with a model where the anesthetic is (1) free in water, (2) weakly bound, and (3) strongly bound to the membrane. A fast exchange exists between the two first sites, but exchange is slow with the third site. Binding of type 3 is observed only at high pH for procaine, whereas it is found both at low and high pH for tetracaine. Calculations of the partition coefficients for the charged and uncharged forms of tetracaine indicate that both sites, 2 and 3, are occupied by the charged form at low pH and by the uncharged form at high pH. The partition coefficient for the weakly bound species was estimated from an analysis of the dependence of line width on the lipid to water ratio. The NMR data suggest that the binding sites for the strongly bound charged and uncharged species are different, the former probably being closer to the membrane-water interface. Estimates of molecular order parameters for the strongly bound species indicate that it is located with its long molecular axis approximately parallel to the director for ordering of the fatty acyl chains. A small increase in lipid ordering by tetracaine is observed at low pH, as evidenced by 2H NMR of the deuterated N-methyl groups of phosphatidylcholine; the reverse occurs at high pH. PMID- 6257350 TI - The use of bee venom melittin to assess the topography of membrane vesicles derived from Paracoccus denitrificans. AB - There exists considerable controversy regarding membrane topography in vesicles derived by osmotic lysis of spheroplasts of Gram-negative bacteria. It has been reported by others that bee venom can be used to quantitate the portion of a heterogeneous vesicle population with an inside-out orientation by determining the degree of loss of crypticity of NADH dehydrogenase activity. We have demonstrated that a major component of bee venom, melittin, causes an increase in the activity of several different respiratory enzymes in isolated membrane vesicles of Paracoccus denitrificans. The degree of stimulation produced by melittin is dependent upon (i) the nature of the respiratory substrates, (ii) the pH, (iii) the presence of Mg2+, (iv) the melittin: membrane protein ratio, and (v) the growth history of the cells from which the membrane vesicles were derived. Melittin-induced enhancement of TMPD:ascorbate and cytochrome c oxidase activities cannot be accounted for by increased accessibility of nonpermeant substrate to the interior of the vesicle. The stimulatory effect of melittin may rely in part on its ability to alter the proton permeability of the membrane thereby abolishing respiratory control. Collectively these observations call into question the usefulness of bee venom melittin in quantitative analyses of membrane topography. These results are consistent with the postulated existence of a homogeneous vesicle population in which the topography of the NADH dehydrogenase is different from that of the intact cell. PMID- 6257351 TI - Inhibition by orthophosphate esters of glucose-6-phosphatase. AB - Inhibition of rat liver microsomal glucose-6-phosphatase (D-glucose-6-phosphate phosphohydrolase, EC 3.1.3.9) by orthophosphate and organophosphate esters was examined at pH 6.0 and 7.5 with and without enzyme pretreatment with 0.2% (w/v) deoxycholate. Inhibition by orthophosphate and monoethyl phosphate was competitive with respect to glucose-6-P while inhibition by mono- and di-phenyl phosphate was of the mixed type. Monoalkyl phosphates were more effective inhibitors than the analogous di- and tri-alkyl phosphates and deoxycholate potentiated the inhibitory effects. Mono- and di-phenyl phosphates were more effective inhibitors than triphenyl phosphate, and deoxycholate decreased these inhibitory effects. The results are interpreted in terms of inhibitor and deoxycholate interactions with the enzyme. PMID- 6257352 TI - Purine ribonucleoside and deoxyribonucleoside kinase activities in thymocytes. Specificity and optimal assay conditions for phosphorylation. AB - The optimal assay conditions and specificity for the principal reactions of purine nucleoside phosphorylation were studied in mouse thymocytes. The following relative activities were obtained for the nucleoside substrates: adenosine, 100; deoxyguanosine, 24; and deoxyadenosine, 14. The phosphorylation of adenosine, 45 microM, was optimal between pH 5.8 and 6.0 with a millimolar Mg:ATP ratio of 1:5. This activity was insensitive to inhibition by other nucleosides and dCTP. Optimal phosphorylation of deoxyguanosine, 350 microM, occurred at pH 8.4 with a millimolar Mg:ATP ratio of 10:3.5. Phosphorylation of 80 microM deoxyguanosine was inhibited approximately 90% by 10 microM deoxycytidine or dCTP and was inhibited 70% by 200 microM deoxyadenosine but unaffected by adenosine. Deoxyadenosine, 450 microM, phosphorylation was optimal between pH 6.5 and 8.5 with a millimolar Mg:ATP ratio of 5:1. Phosphorylation of deoxyadenosine, 100 microM, was partially inhibited by 200 microM adenosine, 34%; 200 microM deoxyguanosine, 10%; and 100 microM deoxycytidine or dCTP, 33%. Only deoxyadenosine phosphorylation was inhibited by 200 microM deoxyinosine, 10%. These results and those obtained from isokinetic sucrose density gradient analysis are consistent with there being a specific adenosine kinase, a faster sedimenting deoxycytidine kinase of broad specificity which also catalyzes the phosphorylation of deoxyguanosine and deoxyadenosine, and a specific deoxyguanosine kinase sedimenting more rapidly than either of the other activities. PMID- 6257353 TI - Enhanced sensitivity of tumorigenic cells to rapid rounding induced by phenylalaninol. AB - This study describes a rounding reaction induced in mammalian cells by the addition of phenylalaninol. In the Chinese hamster ovary tsH1 line the rounding occurred rapidly with a half time of 1 min at 25 mM phenylalaninol. After the removal of phenylalaninol, the rounding was reversed, leading to the reflattening of the cells with a half-time of 3.5 min. Rounding was inhibited by dibutyryl cAMP and testosterone, and reflattening by cytochalasin B. Either in the case of the tsH1 line and its growth-control revertant GRC+L-73, or in the case of SV40 transformed and untransformed human WI-38 cells, the transformed cells displayed a weakened resistance toward rounding. Likewise rat cells transformed by th highly oncogenic adenovirus-12 were more sensitive to rounding than cells transformed by the poorly oncogenic adenovirus-5, which in turn were more sensitive than untransformed cells. However, drug-resistant cell-surface mutants of the Chinese hamster ovary GAT- line also exhibited an altered sensitivity to rounding. These findings suggest that more than one cellular component determines cellular sensitivity to phenylalaninol-induced rounding. One of these components is specifically altered, giving rise to an enhanced sensitivity, in the course of tumorigenic transformation. PMID- 6257355 TI - Isolation of deoxyribonuclease II from bovine intestinal mucosa. AB - Musoca from bovine small intestine was homogenized in Krebs-Ringer phosphate buffer, pH 7.8 the homogenate centrifuged at 16300 X g, and the supernatant solution filtered through cheesecloth to remove lipid material. The filtrate was centrifuged at 105000 X g and the supernatant solution chromatographed on DEAE cellulose. The major peak of DNase II activity, eluted with 20 mM phosphate - 10 mM EDTA buffer, pH 7.8, was purified further by ion-exchange chromatography on CM cellulose and gel filtration on Sephadex G-100. The enzyme was purified 78-fold in 13% yield. Evidence was adduced to indicate that the second minor peak of DNase II activity, eluted from the DEAE-cellulose by a potassium chloride gradient in the 20 mM phosphate - 10 mM EDTA buffer, was an artifact arising from the presence of significant amounts of DNA in the 105000 X g supernatant. The enzyme degraded DNA endonucleolytically to 3'-PO4, 5'-OH oligonucleotides and is similar in its properties to DNase II from other tissues. PMID- 6257354 TI - Oxidation of methionine residues in lutropin. AB - Bovine lutropin and its subunits were submitted to oxidation by sodium periodate or chloramine T. Methionine residues were easily oxidized but partial destruction of fucose was observed. After oxidation treatment most of the lutropin exhibits the same elution volume in gel filtration as the native hormone. Sucrose gradient sedimentation or gel filtration experiments show however that the oxidation of isolated subunits is accompanied by aggregation of conformational changes even in the case of porcine beta subunit which contains only one methionine residue, unit and intact alpha subunit exhibit very low residual activity. PMID- 6257356 TI - Histamine receptors and cyclic AMP. AB - The identification and characterization of histamine receptors in the organ systems of various species has been made possible in recent years by the introduction of relatively selective agonists and antagonists of H1 and H2 receptors. H2 receptors have now been clearly demonstrated in gastric mucosa, heart, rat uterus, brain, and adipose tissue. Less well-defined H2 receptor systems have also been described in the vasculature, bronchioles, and other smooth muscles as well as in the thyroid gland and lymphocytes. In tissues where it has been examined a close correlation between H2 receptors and the adenylate cyclase--cyclic AMP system has been found. With the exception of the central nervous system stimulation of H1 receptors does not seem to be involved with cyclic AMP. In the case of the brain the H1 receptor stimulation of adenylate cyclase can be differentiated from H2 receptor stimulation of the enzyme by the use of blocking agents and by the fact that the H1 receptor response is enhanced in the presence of adenosine. Studies of the involvement of histamine with the adenylate cyclase--cyclic AMP system have been concentrated on such tissues as gastric mucosa, heart, rat uterus, brain, and adipose tissue. The present review will concentrate on the literature concerning those tissues. PMID- 6257357 TI - Purification and partial characterization of a 33 000 molecular weight endonuclease associated with human adenovirus type 5. AB - An endonuclease activity has been purified from human adenovirus type 5 (HAd5) virions and HAd5-infected cell extracts. The endonuclease activity is associated with a monomeric protein of molecular weight approximately 33 000. The endonuclease activity is more active at pH 4.5 than pH 7.2. Incubation of the enzyme at room temperature for periods of longer than 96 h results in a substantial increase in activity. The endonuclease activity is sensitive to EDTA at concentrations 10mM or greater but is insensitive to 500 mM NaCl. Immunological analysis with endonuclease-specific antiserum indicates that the endonuclease may be a host cell derived, viral modified, and incorporated protein. PMID- 6257358 TI - Plasmid detection in a bacteriocinogenic strain of Clostridium perfringens. AB - Bacteriocinogenic Clostridium perfringens, strain 28, harboured plasmid DNA detectable by dye-bouyant density-gradient centrifugation. This plasmid DNA was absent from an ultraviolet light cured variant which had simultaneously lost its immunity and ability to produce bacteriocin. Agarose gel electrophoresis of the plasmid DNA revealed at least six bands but denaturation experiments suggested three plasmids occurring in more than one conformation. Electron microscopy revealed three major size distributions of circular DNA of molecular weights 1,5,6, and 7.1 megadaltons. Some evidence suggests that the 5.6 megadalton plasmid may control bacteriocin 28 production. PMID- 6257359 TI - Cyclic adenosine 3',5'-monophosphate binding protein in developing myxospores of Myxococcus xanthus. AB - The interaction of cyclic adenosine 3',5'-monophosphate (cAMP) with specific protein molecules was examined in the high-speed supernatant fraction of extracts made at stages throughout glycerol-induced myxospore development in Myxococcus xanthus. Experiments using 8-azido[32P]cAMP, a photoaffinity analogue of cAMP, and SDS - polyacrylamide gel electrophoresis showed that the nucleotide interacts with only a single protein band of 12 500 molecular weight. Both the identiy and amount of this protein remained constant throughout development. The binding protein was specific for cAMP; other nucleotides did not compete with cAMP for binding sites. A Scatchard analysis showed evidence of only a single class of binding sites with a high affinity for cAMP. PMID- 6257360 TI - Isozymes of alpha-galactosidase from Bacillus stearothermophilus. AB - Two molecular forms of alpha-galactosidase (EC 3.2.1.22) synthesized constitutively by Bacillus stearothermophilus, strain AT-7, have been purified. alpha-Galactosidase I (with the substrate p-nitrophenyl alpha-D-galactopyranoside (PNPG)) has a pH optimum of 6 and half-life at 65 degrees C of > 2 h at low protein concentration. alpha-Galactosidase II has a pH optimum of 7 with PNPG and a half-life at 65 degrees C of about 3 min. The isozymes also differ with respect to their Km with PNPG and melibiose. Both enzymes are inhibited competitively by D-galactose, melibiose, and Tris. With the beta-glycosides cellobiose and lactose either noncompetitive or mixed-type inhibition is observed, with the pattern dependent on both the pH and the isozyme. The two isozymes have similar Arrhenius activation energies (about 20 kcal/mol, 1 kcal = 4.184 kJ). Their molecular weights, estimated by disc gel electrophoresis, are alpha-galactosidase I, 280 000 +/- 30 000 and alpha-galactosidase II, 325 000 +/- 15 000. Dodecyl sulfate gel electrophoresis gave a single band for each enzyme. The respective molecular weights, 81 000 +/- 500 for alpha-galactosidase I and 84 000 +/- 500 for alpha galactosidase II, suggest that both enzymes consist of four subunits. PMID- 6257361 TI - Extracellular nucleases of Lysobacter enzymogenes: production of the enzymes and purification and characterization of an endonuclease. AB - Lysobacter enzymogenes produced a nonspecific extracellular nuclease and an extracellular RNAase when grown in tryptone broth. Both enzyme activities appeared after the exponential growth phase of the organism. The addition of RNA to the medium specifically inhibited the production of the nuclease and the addition of phosphate prevented the synthesis of the RNAase. DNA had no effect on the enzyme production. The Lysobacter nuclease was purified 274-fold and its molecular weight was estimated to be between 22 000 and 28 000. Freshly purified nuclease showed one major protein band and one major activity band on polyacrylamide gels, whereas two major bands were seen after prolonged storage of the enzyme. The nuclease was most active at pH 8.0 and required Mg2+ or Mn2+. Little activity was obtained in the presence of Ca2+. The enzyme degraded double stranded DNA more rapidly than single-stranded DNA or RNA and was essentially inactive with poly(A) or poly(C) as the substrate. Extensive hydrolysis of double stranded DNA by the enzyme yielded oligodeoxyribonucleotides with terminal 5' phosphate groups. The Lysobacter RNAase appeared to have a molecular weight approximately twice that of the nuclease and was specific for ribonucleotide polymers. PMID- 6257362 TI - Hydrogen metabolism of Azospirillum brasilense in nitrogen-free medium. AB - Production of H2 by Azospirillum brasilense under N2-fixing conditions was studied in continuous and batch cultures. Net H2 production was consistently observed only when the gas phase contained CO. Nitrogenase activity (C2H2 reduction) and H2 evolution (in the presence of 5% CO) showed a similar response to O2 and were highest at 0.75% dissolved O2. Uptake hydrogenase activity, ranging from 0.3 to 2.5 mumol H2/mg protein per hour was observed in batch cultures under N2. Such rates were more than sufficient to recycle nitrogenase produced H2. Tritium-exchange assay showed that H2 uptake was higher under Ar than under N2. Uptake hydrogenase was strongly inhibited by CO and C2H2. Cyclic GMP inhibited both nitrogenase and uptake hydrogenase activities. PMID- 6257363 TI - Ultrastructure of sporulating cells of Clostridium perfringens type A grown in the presence of raffinose. AB - Seven-hour sporulating cells of Clostridium perfringens type A strain NCTC 10240 grown in the presence of raffinose versus starch were larger, produced a thicker cortex, and were altered in spore coat structure. Strain NCTC 8798 possessed an expanded subcoat region and (or) produced coat fragments when grown in the presence of raffinose. PMID- 6257364 TI - A survey of Clostridium perfringens enterotoxin antibody in human and animal sera in western Canada. AB - Sera from human, cattle, sheep, swine, and horse populations in western Canada were tested for the presence of Clostridium perfringens enterotoxin antibody by the passive hemagglutination (PHA) test, supplemented by an immunodiffusion test and by counterimmunoelectrophoresis. A total of 224 human, 345 cattle, 165 sheep, 620 swine, and 768 horse serum samples were examined. Low-titer reactions in the PHA test were detected in human, cattle, horse, and swine sera, in that order, with no titers demonstrated in sheep. The titers in human sera ranged up to 1:128 and three of these samples were also positive in the other two serological tests. The significance of this antibody is not clear, but it is suggested that the low prevalence of the antibody may reflect a low prevalence of enterotoxigenic C. perfringens strains in western Canada. Such serological surveys may be applicable to epidemiological studies involving enterotoxigenic C perfringens. PMID- 6257365 TI - Dietary fibre. PMID- 6257366 TI - The role of dietary fibre in the human colon. AB - Several effects of dietary fibre on colonic function have been documented by experiment or deduced from epidemiologic observation. The magnitude of these changes depends on the source and the physical and chemical composition of the fibre used, and on the individual response of the subjects. Three theories of the mode of action of fibre are discussed; they relate to the water-holding capacity of fibre, the production of short-chain fatty acids from fibre in the colon and the alteration by fibre of the colonic microflora. PMID- 6257367 TI - Breast cancer, cough and vesicular eruptions. PMID- 6257368 TI - Effects of dietary fibre on serum lipid levels and fecal bile acid excretion. AB - Epidemiologic studies have suggested that dietary fibre protects humans against coronary heart disease, but interpretation of the data is confounded by coexisting differences in both dietary and environmental variables. The hypocholesterolemic action of dietary fibre varies: in general mucilaginous fibres such as pectin and oat bran are more effective than particulate fibres such as wheat bran. Although the mechanism of action of mucilaginous fibres is not completely understood, there is evidence that they induce small increases in the fecal excretion of bile acids and neutral steroids that are not fully compensated for by de novo cholesterol synthesis. PMID- 6257369 TI - Cyclic nucleotides in biological fluids in hepatocellular carcinoma. AB - To investigate the prediction that urinary cGMP (UcGMP) and cAMP (UcAMP) excretion is altered in a manner consistent with unregulated cell growth in hepatocellular carcinoma (HCC), we studied 31 patients with this disease, 25 without apparent disease, 16 with various hepatic diseases, and 16 with nonhepatic neoplasms. Results were expressed as UcGMP excretion per 100 ml glomerular filtration because reduced creatinine excretion in patients with muscle wasting or renal dysfunction may spuriously elevate UcGMP. UcGMP excretion was elevated in 80% of patients with HCC, 75% of patients with hepatic disease and 68% of patients with other neoplasms. Mean values for UcAMP excretion did not differ significantly from normal values. Plasma and ascitic fluid cGMP concentrations in HCC and hepatic diseases were raised. These results support the hypothesis of a shift in cyclic nucleotide metabolism toward cGMP in malignant diseases. However, UcGMP measurement does not detect progression of cirrhosis to HCC. PMID- 6257370 TI - Estrogen receptors in male breast cancer: clinical and pathologic correlations. AB - Breast cancer tissue from 12 male patients was evaluated for the presence of estrogen receptors (ER), and at least 10 of 12 were found to be high in ER (ER+). A combination of previously published cases and our own experience indicates that 80% of patients (37/47) have ER+ tumors. This incidence of ER positivity in men is greater than that in women with breast cancer. Clinical responses to hormonal therapy have been observed in the ER+ patients but not in one ER--patient. Measurement of ER may be clinically important in men with breast cancer. PMID- 6257371 TI - Cytologic characteristics of oat-cell carcinoma of the lung in relation to the effect of chemotherapy. AB - The cytologic study of the effect of chemotherapy was performed in oat-cell carcinoma of the lung. Cellular characteristics of tumor cells obtained by brushing via bronchoscopy were compared between responders (13 patients in complete and partial regressions) and nonresponders (13 patients with no response) treated with cyclophosphamide. The tumor cells in the responders more frequently showed finely granular chromatin evenly distributed throughout the nuclei. The tumor cells in nonresponders showed predominantly either deeply stained nuclei with coarsely granular chromatin distributed evenly or pale nuclei with unevenly distributed chromatin. These findings were also applied in the evaluation of the effect of combination chemotherapy. The nuclear chromatin pattern from oat-cell carcinoma of the lung may be an indicator to predict the degree of response to chemotherapy. PMID- 6257372 TI - Comparison of symptomatic and prophylactic irradiation of brain metastases from oat cell carcinoma of the lung. AB - In this analysis, the results of brain irradiation of 39 patients with symptomatic brain metastases from oat cell carcinoma of the lung were compared with the published results of patients whose brains were irradiated prophylactically. The goals were: (1) to substantiate a clinical impression that patients with symptomatic brain metastases respond well to radiation and often experience no further neurologic deterioration until death; and (2) to compare the outcomes of symptomatic and prophylactic radiation of the brain for oat cell carcinoma of the lung. Of 39 patients with proven brain metastases who received cranial irradiation, 25 (64%) achieved complete palliation and remained free of neurologic symptoms, 4/4 (100%) achieved complete palliation; for moderate symptoms, 12/15 (80%); and for severe symptoms, 9/20 (45%). A summary of 12 reports from the literature shows that for patients with oat cell carcinoma of the lung receiving prophylactic cranial irradiation, the incidence of brain metastases is 28/525 (5%), while for patients receiving no prophylactic therapy it is 51/223 (23%). When the results of symptomatic and prophylactic cranial irradiation were compared, it was found that symptomatic irradiation controls central nervous system disease, as well as prophylactic therapy, while eliminating the need for brain irradiation in three-fourths of the patients. PMID- 6257373 TI - Hairy cell leukemia: establishment of a cell line and its characteristics. AB - A hairy cell leukemia (HCL) line, ZK-H, was established from peripheral blood of a 69-year-old male patient. The ZK-H cells and the patient's original hairy cells shared the same surface properties; both possessed membrane-bound IgG with kappa light chains and villous surface structures. The ZK-H line carried Epstein-Barr virus (EBV)-determined nuclear antigen, but the patient's fresh leukemic cells lacked this antigen. Morphologically, the ZK-H cells appeared lymphoblastoid and more primitive than the preculture cells. The ZK-H line had a hyperdiploid chromosome constitution of 47 and trisomy no. 2. The presence of membrane-bound immunoglobulin and of B-cell tropic EBV in this cell line provides further evidence for the B-cell nature of HCL in this patient PMID- 6257374 TI - Progress in the chemotherapy of small cell carcinoma of the lung. AB - A comparison was made between six different approaches to the chemotherapy of small cell carcinoma of the lung. The value of single-agent chemotherapy was compared to combination chemotherapy and radiation therapy, and with cyclic alternating combination chemotherapy in 161 patients. Cyclic alternating chemotherapy with modest radiation therapy to the primary site provided significant advantages over single-agent or combination chemotherapy. A combination of VP-16 + Adriamycin + vincristine seemed particularly effective in inducing an initial objective tumor response rate of 83%, with a projected median survival of 13.2 months. Of patients treated with cyclic alternating therapy, 51% were alive at one year. It thus appears that where complete response is achieved, prolonged disease-free survival can be expected. PMID- 6257375 TI - Relationship of ectopic ACTH production to tumor differentiation: a morphologic and immunohistochemical study of prostatic carcinoma with Cushing's syndrome. AB - A case of Cushing's syndrome in a patient with an ACTH-producing prostatic carcinoma is presented. Initial transurethral biopsy showed a moderately well differentiated adenocarcinoma. The development of Cushing's syndrome was associated with a change in the morphology of the tumor; repeat transurethral prostatic biopsy and autopsy showed an admixture of moderately well differentiated adenocarcinoma and anaplastic carcinoma. Immunoperoxidase studies revealed ACTH only within the anaplastic component of the tumor, which also showed strong argyrophilia. Electron microscopic studies revealed abundant dense core granules within the anaplastic portion of the tumor with only very scanty granules in the differentiated portion. This case strongly supports the contention that cells with APUD characteristics can differentiate within epithelial tissues of multiple embryologic origins, and that the possession of APUD features does not necessarily imply origin from any specific neuroendocrine progenitor cell. PMID- 6257376 TI - The practicality of chronic hepatic artery infusion therapy of primary and metastatic hepatic malignancies: ten-year results of 124 patients in a prospective protocol. AB - Ten-year results are presented of 124 patients with malignancy apparently limited to the distribution of the hepatic artery, treated to prospective protocol with continuous infusion of 5-FUdR through an hepatic artery catheter. Nearly all patients had moderate to massive hepatic replacement. Of 88 patients with colorectal carcinoma, 64 (73%) had clinically objective and subjective remission. Median survival for responders was 13 months; for the entire group, ten months. Of 13 patients with hepatoma, nine had clinically significant regression with a median survival of 11 months. Ten patients had carcinoma of the gall bladder or bile duct with seven obtaining clinically significant regression. Complications encountered are discussed and are similar to other series. Of the patients experiencing clinically significant remission, all but one reached the complete independence performance status, and 84% reached normal activity levels. Thus, for hepatic localized tumor, this therapy is worthwhile and practical. PMID- 6257377 TI - Histology, ultrastructure, and tissue culture of human insulinomas. AB - Four cases of insulinoma were studied by electron microscopy. Insulinoma cells were also cultured in vitro. Ultrastructure was correlated with the content of immunoreactive insulin (IRI) and the percentage of proinsulin-like component (PLC) in the serum, tumors, and culture fluid. The number and shape of secretory granules varied amont the samples, from the tumors having typical beta granules to poorly granulated tumors having a few atypical granules. High levels of IRI in the serum and a high percentage of PLC in the serum and tumor, found in a patient with a virtually agranular tumor, combined with the fact of rare occurrence of emiocytosis, suggest a defective insulin storage mechanism and alternative routes of insulin release in insulinoma cells. PMID- 6257378 TI - Effect of short-chain fatty acids on Epstein-Barr virus early and viral capsid antigen induction in P3HR-1 cells. AB - The effects of short-chain fatty acids were assayed for their capacity to induce Epstein-Barr virus (EBV) from the EBV genome-carrying human lymphoblastoid P3HR-1 cells. Not only the n-butyric acid, the activity of which is now well established, but also the n-valeric acid was found to induce EBV-associated early antigen (EA) and viral capsid antigen (VCA) at an appreciable level. Similarly, i valeric acid showed a considerably lower, but significant, level of this activity, while the i-butyric acid was inactive. All other fatty acids with either a chain shorter than butyric or longer than valeric showed only a marginal effect or none at all. Thus, the decisive factor for EBV-inducing capacity of the fatty acids concerns adequate length and configuration of the basic structure of the molecules. PMID- 6257379 TI - Utilization of a human tumor cloning system to monitor for marrow involvement with small cell carcinoma of the lung. AB - We have compared the sensitivities of two methodologies for determining bone marrow involvement by small cell lung cancer. These methodologies included histological examination of marrow aspirations and biopsies versus growth of tumor colonies in soft agar. There were four instances in which histological study of the marrow aspirate (and biopsy) revealed metastatic small cell lung cancer. All four of the specimens formed colonies in soft agar. Thirty-four of 37 histologically negative aspirations and biopsies) showed no growth in the soft agar system. However, three histologically negative specimens formed colonies in soft agar. The cells growing in these colonies were documented to be small cell lung cancer by histology and growth in nude mice. We conclude that small cell lung cancer metastatic to bone marrow will form colonies in soft agar. Additional study is needed to determine if the soft agar system is indeed more sensitive than routine histology in detecting small cell lung cancer metastatic to bone marrow. PMID- 6257380 TI - In vitro chemical mutagenesis and viral transformation of a human endothelial cell strain. AB - We have established and characterized a diploid cell strain of normal human endothelial cells, RuBa 7E. RuBa 7E cells have an average cloning efficiency of 20% during early passages and undergo approximately 50 doublings in vitro before senescing spontaneously. At confluence, RuBa 7E cells form a homogeneous monolayer of flat polygonal cells. RuBa 7E cells react positively with antibody to human endothelial-specific Factor VIII. The toxic and mutagenic effects of N methyl-N'-nitro-N-nitrosoguanidine on RuBa 7E cells were studied and are similar to those reported for diploid human fibroblasts. Mutant cells lacking hypoxanthine-guanine phosphoribosyltransferase were selected by their resistance to 6-thioguanine. The spontaneous incidence of mutants was less than or equal to 6 X 10(-6), and the induced incidence was 4.4 X 10(-4) at a survival frequency of 0.05. All 17 mutants that were tested lacked detectable hypoxanthine-guanine phosphoribosyltransferase activity, and none grew in medium containing azaserine and hypoxanthine. Autoradiography showed that mutant cells incorporated radioactive adenine but did not incorporate radioactive hypoxanthine. Unlike human fibroblasts, in which the recovery of 6-thioguanine-resistant mutants is reduced by contact feeding when the inoculum size during selection is increased above 10(4) cells per P60 dish, 5 to 10 X 10(4) RuBa 7E cells can be plated per P60 dish without reducing mutant recovery. This apparent lack of plating density suppression of mutant recovery makes RuBa 7E cells a comparatively compact and economical system for quantifying mutagenesis in diploid human cells. In order to determine whether RuBa 7E cells would undergo a distinct morphological transformation toward cancer in vitro, we infected them with SV40. As early as 14 days postinfection, discrete foci of morphologically transformed, mitotically active cells were seen against a monolayer background of normal cells when cultures were maintained in medium with low serum. Seven of the 33 foci which were obtained were studied for SV40-specific viral T-antigen, and all were positive. The facility with which RuBa 7E cells can be mutagenized and the ease with which morphological transformants can be identified make these cells potentially useful for studies comparing the mutagenic and transforming effects of chemicals and other agents on diploid human cells. PMID- 6257381 TI - Formation of acetylpolyamines and putrescine from spermidine by normal and transformed chick embryo fibroblasts. AB - Polyamine uptake and metabolism were studied in cultures of normal and Rous sarcoma virus-transformed chick embryo fibroblasts. The uptake of radioactive putrescine and spermidine by the transformed cells was faster than that of the normal controls. The amount of radioactive putrescine and polyamines taken up by the transformed cells also exceeded that observed with normal fibroblasts. The intracellular levels of putrescine, spermidine, and spermine were considerably higher in the transformed cells than in the normal controls. Radioactive spermidine was converted into N-acetylputrescine and N1-acetylspermidine by the transformed cells. The extent of this conversion by the normal fibroblasts was significantly lower. Radioactive putrescine and spermine were also formed from radioactive spermidine added to cultures of transformed fibroblasts. The rate of this conversion was significantly slower in normal chick embryo fibroblasts. PMID- 6257382 TI - Influence of bursectomy on bone growth and anemia induced by avian osteopetrosis viruses. AB - This study examines the contribution of the bursa of Fabricius to the pathogenic manifestations of two myeloblastosis-associated viruses which primarily cause osteopetrosis [MAV-1(O) and MAV-2(O)]. MAV-2(O) infection of surgically bursectomized 1-month-old chicks resulted in a rapidly fatal anemia whereas infection of untreated chicks of the same age resulted in a transient drop in hematocrit. Surgical bursectomy of embryos before or after embryonal infection with MAV-2(O) did not alter the course of osteopetrosis, indicating that the bursa was not a source of target cells. Bursectomy prolonged the period of susceptibility to MAV-2(O) induced osteopetrosis until one day posthatching; untreated chicks were not susceptible to osteopetrosis induction at that age. MAV 1(O) infection of eight-day-old bursectomized chicks resulted in osteopetrosis in the absence of anemia; untreated eight-day-old chicks infected with MAV-1(O) showed no effects of virus infection. A role for the bursa in MAV-2(O) infection was found in the participation of neutralizing antibodies in the recovery from anemia. A single dose of antiviral antibody was found to prevent the appearance of anemia. The protective effect of antiviral antibody was dose dependent, and antiserum administration had to be initiated within three days after virus in order to be effective. Antiviral antibody against MAV-1(O) did not protect against MAV-2(O)-induced anemia, suggesting subgroup specificity. These results suggest that the bursa does not provide a stem cell which participates in the bone hyperplasia induced by MAV-1(O) and MAV-2(O). Rather, the humoral antibodies provided by cells derived from the bursa may serve to eliminate viremia and limit virus-specific cytopathogenic effects. PMID- 6257383 TI - Excision of ultraviolet damage and the effect of irradiation on DNA synthesis in a strain of Bloom's syndrome fibroblasts. AB - We have studied repair of ultraviolet light (UV)-induced damage in a strain of Bloom's syndrome cells which we have shown to be defective in host cell reactivation of UV-irradiated herpes simplex virus. Excision repair was monitored by following loss of sensitivity of DNA in permeabilized cells to digestion by the Micrococcus luteus UV endonuclease preparation. The Bloom's syndrome fibroblasts apparently removed endonuclease-sensitive sites from the DNA slightly less efficiently than did normal strains. After 24 hr, 38% of the sites remained in the Bloom's syndrome cells in comparison with 16% in normal fibroblasts. DNA newly synthesized in UV-irradiated Bloom's syndrome cells sedimented less far into alkaline sucrose gradients than did DNA from similarly treated normal cells. In other respects, including the effect of caffeine exposure, DNA synthesis in Bloom's syndrome cells was indistinguishable from that in normal cells. We were therefore able to detect only minor defects in the repair of UV-induced damage in Bloom's syndrome fibroblasts. This is consistent with the normal survival exhibited by these cells. The defect in excision repair may, however, be sufficient to allow the cellular repair capacity to become saturated at high infecting multiplicities of UV-irradiated herpes simplex virus. PMID- 6257384 TI - Subset of spleen lymphocytes from BALB/cCrgl mice stimulated by mouse mammary tumor virus. AB - Lymphocytes from BALB/cCrgl mice react to mouse mammary tumor virus-associated antigen(s) when tested in in vitro blastogenic transformation assays. These mice have a low incidence (less than 1%) of spontaneous mammary tumors and are free from complete mammary tumor virions. We have studied the nature of the lymphoid cells mediating the lymphocyte transformation reaction to purified mammary tumor virus. With the use of nylon wool columns, the responder cells were found to belong to the nylon-adherent population. The T-lymphocytes were not stimulated by mammary tumor virus even in the presence of added macrophages. These results were reconfirmed with treatments of spleen cells with either anti-surface immunoglobulin and complement or anti-Thy 1 antigen and complement. Thus, B-cells seem to be the lymphoid population responsive to mammary tumor virus-associated antigen(s) in the spleen of BALB/cCrgl. The cause of this reactivity may be a result of any of the following: (a) horizontal transmission; (b) activation of spleen cells by viral host cell contaminants in mammary tumor virus preparations; (c) a nonspecific mitogenic reaction exerted by the virus in the system; (d) sensitization to mammary tumor virus-associated antigen(s) due to the expression of an endogenous virus. We present here data arguing against the first three possibilities. In recent work, we found evidence supporting the expression of mammary tumor virus-related antigen(s) on lymphoid cell surfaces of BALB/cCrgl. From these studies, we propose that the responses seen in our in vitro assays may represent a sensitization event resulting from exposure to an endogenous mammary tumor virus gene product. PMID- 6257385 TI - Correlation of collagen synthesis and procollagen messenger RNA levels with transformation in rat embryo fibroblasts. AB - A line of normal rat embryo fibroblasts was transformed with N-methyl-N'-nitro-N nitrosoguanidine (a chemical carcinogen), SV40 and polyoma virus (two DNA viruses), and Rous sarcoma virus (an RNA tumor virus). In this study, we report a comparison of the levels of collagen synthesis and procollagen messenger RNA (mRNA) in 13 lines selected after transformation with one of these agents. Collagen synthesis and procollagen mRNA levels were compared with the degree of transformation determined from morphology, saturation density, growth in agarose, and tumorigenicity in nude mice. Each class of transformants had a characteristic level of collagen synthesis; this level correlated inversely with the degree of transformation of the rat embryo fibroblasts. In N-methyl-N'-nitro-N nitrosoguanidine and SV40 transformants which were moderately transformed, collagen synthesis was hardly affected, but, in polyoma virus and Rous sarcoma virus transformants which were more severely transformed, collagen synthesis was 30 to 48% and 12 to 25%, respectively, of control levels. Type I procollagen mRNA activity measured in RNA from nine of the lines by an in vitro translation assay also decreased with increasing severity of transformation. Procollagen mRNA levels were reduced to about one-half of control levels in one SV40 transformant and to 17 to 23% of controls in polyoma virus and Rous sarcoma virus transformants. We conclude that, in this series of rat fibroblast lines, transformation with different agents resulted in characteristic levels of collagen synthesis and that collagen synthesis was most reduced in the cells which were most transformed by other criteria. PMID- 6257386 TI - Fine structural evidence on the origin of gonadotropin-induced ovarian tumors in mice. AB - A nonluteinized granulosa cell ovarian tumor and a purely luteinized ovarian tumor, induced by gonadotropin stimulation in mice, were studied ultrastructurally to obtain evidence concerning the possible origin of these tumors, whether from granulosa cells only or from granulosa and theca. Evidence including the presence of cells sharing features of both nonluteinized and luteinized cells, the presence of desmosomes and other junctional complexes in both cell types, and the presence of partially extracted lipid droplets in the luteinized cells suggests that the luteinized cells represent granulosa-lutein cells rather than theca-lutein cells. These findings are consistent with the concept that these tumors represent a spectrum of differentiation from nonluteinized granulosa cells to luteinized granulosa cells. The lack of theca and theca-lutein cells in both tumors implies that theca cells are not involved as progenitor cells. PMID- 6257387 TI - Thymidine and hypoxanthine requirements of normal and malignant human cells for protection against methotrexate cytotoxicity. PMID- 6257388 TI - Biological, immunological, and molecular properties of revertants of cat cells transformed by murine sarcoma virus. PMID- 6257390 TI - cAMP accumulation in developing cultures of chicken embryo brain hemisphera. PMID- 6257389 TI - Phase II evaluation of triazinate in patients with metastatic lung cancer. PMID- 6257391 TI - [Tri-iodothyronine bond to human prostate gland cytosol proteins (author's transl)]. PMID- 6257392 TI - [Colchicine derivatives and their effect on lysosomal enzyme release from polymorphonuclear leukocytes and on intracellular levels of 3',5'cyclic adenosine monophosphate following urate crystal phagocytosis (author's transl)]. PMID- 6257393 TI - Protein phosphorylated by the RSV transforming function. PMID- 6257394 TI - Early precursors in the erythroid lineage are the specific target cells of avian erythroblastosis virus in vitro. AB - In chickens the erythroid differentiation proceeds from stem cells to erythrocytes through several intermediate steps which have been identified in vivo and in vitro. To determine whether Avian erythroblastosis virus (AEV) is able to transform in vitro either one or several types of these precursors, bone marrow cells were separated by physical and immunological methods. It was found that the target cells which could be transformed in vitro by AEV were cells of light density (1.060-1.065 g/cm3), having a modal sedimentation velocity at unit gravity between 4.0 and 6.0 mm/hr, expressing an immature antigen at a low level and a brain-related antigen at a high level. These results indicated that the target cells of neoplastic transformation by AEV were early erythroid precursors, since these precursors shared the same physical and immunological properties with AEV target cells. PMID- 6257395 TI - Intracellular transport of secretory and membrane proteins in hepatoma cells infected by vesicular stomatitis virus. PMID- 6257396 TI - Characterization of protein kinase activity associated with the transforming gene product of Fujinami sarcoma virus. AB - Fujinami sarcoma virus (FSV), a newly characterized avian sarcoma virus, produces a protein of 140,000 daltons (p140) in infected cells. p140 is the product of a fused gene consisting of a part of the gag gene of avian retrovirus and FSV unique sequences which are not related to the src sequences of Rous sarcoma virus. In vivo, p140 was found to be phosphorylated at both serine and tyrosine residues. Immunoprecipitates of p140 with antiserum against gag gene-coded proteins had a cyclic nucleotide-independent protein kinase activity which phosphorylated p140 itself, rabbit IgG of the immune complex and alpha-casein, an externally added soluble protein substrate. The phosphorylation was specific to tyrosine of the substrate proteins. p140 was phosphorylated in vitro at the same two tyrosine residues that were phosphorylated in vivo. The phosphate transferred to tyrosine residues of p140 forms a stable bond: it does not turn over during the kinase reaction, and the 32P-phosphate of p140 labeled in vitro or in vivo is not transferred to alpha-casein. FSV-p140 differs from p60src, the transforming protein of Rous sarcoma virus, in its marked preference of Mn2+ to Mg2+ ions, and in its inability to use GTP instead of ATP as the donor of gamma-phosphate. PMID- 6257397 TI - A strain of Fujinami sarcoma virus which is temperature-sensitive in protein phosphorylation and cellular transformation. AB - Cells infected by one strain of Fujinami sarcoma virus (FSV) are transformed at 38 degrees C but are phenotypically normal at 41.5 degrees C. FSV encodes a 140,000 molecular weight protein (P140) with gag gene-related and FSV-specific peptide sequences. At 41.5 degrees C, P140 is weakly phosphorylated at serine residues, and is inactive in the immune complex protein kinase assay. At 38 degrees C, P140 is highly phosphorylated, contains phosphotyrosine in addition to phosphoserine, and in the immune complex kinase assay becomes phosphorylated at three tyrosine residues. Phosphorylation of cellular polypeptides at tyrosine residues in FSV-infected cells is also temperature-sensitive. These observations indicate that P140 is the transforming protein of FSV and that protein phosphorylation at tyrosine residues is involved in transformation by this virus. PMID- 6257398 TI - Structure of the Abelson murine leukemia virus genome and the homologous cellular gene: studies with cloned viral DNA. AB - Circular double-stranded DNA produced after infection of mouse cells with Abelson murine leukemia virus (A-MuLV) was isolated and cloned in the phage vector Charon 21A. The resulting clones of the A-MuLV genome show homology to the ends of Moloney MuLV and to a 3.5 kb central region containing sequences unique to Abelson virus. A 2.3 kb restriction fragment containing only A-MuLV-specific sequences was subcloned in the plasmid vector pBR322 and used as a probe for the cellular gene that had been acquired by the virus. DNA from all inbred mouse lines examined contains an identical region of homology spread out over 11 to 20 kb. The cellular gene contains intervening sequences which are lacking in the viral genome. Rat, Chinese hamster, rabbit, chicken and human DNA also show homology to the viral probe. PMID- 6257399 TI - Identification of a functional promoter in the long terminal repeat of Rous sarcoma virus. AB - Specific initiation of transcription of Rous sarcoma virus by RNA polymerase II was obtained in a cell-free system using cloned RSV DNA as template. The site of initiation is located in the common "C" region of the long terminal repeat (LTR), 23 bp downstream from the promoter-like sequence TATTTAAG. This finding indicates that the basic information necessary for RSV transcription lies within the viral genome. PMID- 6257400 TI - Integration sites and sequence arrangement of SV40 DNA in a homogeneous series of transformed rat fibroblast lines. AB - The state and organization of viral DNA sequences present in independently isolated rat cell lines transformed with SV40 were investigated using restriction enzyme cleavage of the cellular DNA and blot hybridization with a viral probe. The transformed lines were established under conditions as identical as possible, except for a limited number of variables (multiplicity of infection, physiological state of the cells after infection and procedures used for selecting the transformed derivatives). They were characterized after a limited number of generations in culture. Two distinct types of organization were found: covalently integrated viral genomes were present either as single inserts or as head-to-tail oligomeric structures. The latter was observed among transformants derived from cells maintained after infection under growth-inhibiting conditions (suspension in agarose medium, confluency on a solid substrate). Single inserts were observed only among cell lines isolated after an initial period of active growth. Recurrent patterns of hybridizaton were observed in independently isolated lines, indicating that the sites of the integrative recombinations were close enough, both in the viral and the cellular sequences, not to be distinguished at the level of sensitivity of the technique (more than +/- 100 bp). Among cell lines with multiple integration sites, only part of the inserts were found in several instances to be identical to inserts observed in other transformed lines. PMID- 6257401 TI - Molecular cloning of the "minor" component of the kinetoplast DNA of Trypanosoma lewisi. AB - Kinetoplast DNA was cloned in the pBR322 plasmid using the BamHI site. In situ hybridization of iodinated recombinant DNA showed hybridization grains only in the kinetoplast region. The recombinant DNA was analyzed with restriction enzymes and its base ratio was determined by analytical CsCl density gradient. PMID- 6257402 TI - Alteration of urinary levels of the carcinogen, N-hydroxy-2-naphthylamine, and its N-glucuronide in the rat by control of urinary pH, inhibition of metabolic sulfation, and changes in biliary excretion. AB - The hepatic metabolism of arylamine bladder carcinogens to N-hydroxy arylamine N glucuronides, their excretion in the urine, and their subsequent acidic hydrolysis to highly carcinogenic and reactive N-hydroxy arylamines have been proposed as essential steps in arylamine-induced urinary bladder carcinogenesis. In this study, alteration of urinary pH, inhibition of metabolic sulfation, and blockage of biliary disposition were shown to profoundly affect the urinary excretion of the probable ultimate bladder carcinogen, N-hydroxy-2-naphthylamine (N-HO-2-NA) and its N-glucuronide conjugate. The normal pH of rat urine (6.7) was altered to 5.7 or 7.7 by administration of NH4Cl or NaHCO3 in the drinking water. Subsequent treatment with either 2-naphthylamine (2-NA) or 2-nitronaphthalene (2 NN) resulted in increased urinary levels of free N-HO-2-NA (relative to its N glucuronide) in acidic urines and decreased relative amounts of free N-HO-2-NA in alkaline urines. In addition, 2-NN yielded 5--10-fold greater levels of urinary N HO-2-NA and its N-glucuronide than rats given 2-NA; and 2-NA was not detected as a urinary metabolite of 2-NN. Some 12 additional metabolites of 2-NA and 2-NN were also found. Of these, 2-amino-1-naphthol and its sulfate and glucuronide conjugates were quantitated. From these data, 2-NA and 2-NN appear to share common metabolic pathways which yield free N-HO-2-NA as a putative ultimate urinary bladder carcinogen. Pentachlorophenol, a known inhibitor of hepatic sulfotransferases, was shown to cause a 2--3-fold increase in the urinary levels of N-HO-2-NA N-glucuronide and N-HO-2-NA from 2-NA-treated rats. Similarly, inhibition of the biliary excretion of 2-NA by bile duct ligation resulted in a 6 fold increase in total urinary N-HO-2-NfA. Furthermore, analyses of bile revealed that substantial amounts of N-HO-2-NA N-glucuronide, but not free N-HO-2-NA, were present. The role of urinary versus biliary excretion of N-hydroxy arylamines in relation to bladder and colon carcinogenesis is discussed. PMID- 6257403 TI - Reactions induced in vitro between model DNA and benzo[a]pyrene by near ultraviolet radiation. AB - Near-ultraviolet (300--480 nm wavelength) irradiation of the single-strand polydeoxynucleotide poly[d(A,C,G,T)] and carbon-14 labeled benzo[alpha]-pyrene (B[alpha] P) in aqueous dimethylsulfoxide (DMSO) solution led to appreciable binding of labeled hydrocarbon to the polynucleotide. Nuclease digests of polydeoxynucleotide-B[alpha]P complexes were examined by chromatography on Sephadex LH-20; at high fluences of near-ultraviolet light deoxyguanosine (dG) residues of the polymer were largely destroyed when the hydrocarbon was present. Approximately 85% of the B[alpha] P of the digests were recovered as hydrophilic derivatives not adsorbed by Sephadex LH-20. Elution of the columns with an aqueous-methanol gradient indicated that substances similar to the covalent deoxynucleoside-B[alpha] P adducts formed between microsomally-oxidized B[alpha] P and DNA were likewise present in the digests. When the deoxyadenosine (dA), deoxycytidine (dC) or dG moieties of the polymer were tritium-labeled, substances doubly-labeled with tritium and carbon-14 were found; ratios of the two radioactivities indicated that equimolar amounts of deoxynucleoside and hydrocarbon were present. PMID- 6257404 TI - Benzo[a]pyrene metabolism in organ cultures of human endometrium. AB - Twenty-six specimens of normal human endometrium were obtained for studies of [3H]benzo[alpha]pyrene metabolism in short-term organ culture. The tissues were capable of converting benzo[alpha]pyrene (BP) to oxygenated derivatives which co chromatographed with dihydrodiols, quinones and monohydroxy derivatives of BP. A sulfate conjugate of a monohydroxy BP was also found among the acetone/ethyl acetate soluble products. When the acetone/ethyl acetate soluble metabolites were analyzed using high-pressure liquid chromatography (HPLC), the proportion of metabolites were found to vary greatly from specimen to specimen. Eight women smoked cigarettes but the BP metabolite profiles from organ cultures of endometrial tissue from these women did not differ from those who did not smoke. The average value for sulfate conjugates of monohydroxy BP was significantly lower in endometrial tissue from three postmenopausal women (ages 49, 57 and 58) than among premenopausal women. Specimens from premenopausal women which had been in organ culture for 2 weeks prior to the addition of [3H] BP produced metabolite profiles similar to those of specimens from postmenopausal women with a greatly reduced proportion of BP-phenol sulfate conjugates. These data suggest that the absence of hormonal stimulus (i.e., advanced age or conditions of organ culture) may affect the metabolism of BP in human endometrial tissue. PMID- 6257405 TI - Evaluation of 2,2'-anhydro-1-(3'-Ok-acetyl-beta-D-arabinofuranosyl)-5 iodocytosine hydrochloride and related compounds as antineoplastic and antiviral agents. AB - 2,2'-Anhydro-1-(3'-O-acetyl-beta-D-arabinofuranosyl)-5-iodocytosine (anhydro araIC 3'-acetate), previously synthesized and isolated as a crude product by Moffatt and his coworkers, was purified and characterized. The availability of pure anhydro-araIC 3'-acetate made possible a comparative study of the antineoplastic, antiviral and biochemical potencies of anhydro-araIC 3'-acetate with the structurally related agents 2,2'-anhydro-1-(3'-O-acetyl-beta-D arabinofuranosyl)cytosine (anhydro-araC 3'-acetate) and 2,2'-anhydro-1-(beta-D arabinofuranosyl)-5-iodocytosine (anhydro-araIC). The presence of the 5-iodo substituent and/or the 3'-O-acetyl group on 2,2'-anhydro1-(beta-D arabinofuranosyl)cytosine (anhydro-araC) did not alter the capacity of these agents to exert cytotoxic and antineoplastic activity against L1210, P388, L5178Y and human leukemia cells and against human colon and rectal carcinomas, as well as antiviral activity against herpes simplex virus Type 1. All of the compounds caused inhibition of [3H]thymidine incorporation into the DNA of L1210 cells in culture, with anhydro-araIC 3'-acetate being significantly less inhibitory than the other derivatives. Little or no interference with RNA and protein synthesis was produced by these pyrimidine nucleosides. Both anhydro-araIC 3'-acetate and anhydro-araIC were potent inhibitors of the activity of DNA polymerase alpha from the L1210 leukemia at the nucleoside level, while anhydro-araC 3'-acetate and anhydroaraC were non-inhibitory; none of the agents caused inactivation of DNA polymerase beta. The findings suggest that the antineoplastic and antiviral activities of the 2,2'-anhydro-arabinosylcytosine nucleosides may be the result of biochemical actions different from those of araC. PMID- 6257406 TI - Structure-activity relationships in halogenated biphenyls: unifying hypothesis for structural specificity. AB - Using chlorinated biphenyls as model halogenated aromatic hydrocarbons, in this and previous work we have investigated the specific structural requirements for induction of cytochrome P-448, P-450 and associated monooxygenase activities, and exquisite toxicity in the guinea pig. The requirement of planarity of coplanarity was examined using single crystal X-ray techniques to describe the structure and conformation of PCBs and PBs in the solid state as an approximation of their interactions with a bioreceptor. It was concluded that the most stable conformation of all biphenyls with or without ortho-substitutents is non-planar and that neigher planarity nor symmetry is an inherent requirement for receptor binding. The basic requirement for toxic structures was the availability of at least three lateral bromines or four lateral chlorines arranged in about a 3 X 10 A triangle or box, respectively. The underlying factor in the apparent symmetry requirement (as determined by the number and positions of halogens) is net polarizability of the molecule. Sufficient polarization for binding requires four lateral chlorines or three lateral bromines. Planarity or coplanarity of rings is necessary only to effect juxtaposition of the four lateral chlorines, and binding is therefore facilitated by an increased population of planar conformers. The population of planar conformers in biphenyls is in turn reduced by the degree of ortho substitution and hindrance to rotation about the pivot bond. Net polarizability is increased by the buttressing effect of adjacent chlorines or bromines, especially when ortho positions are involved. Coplanarity effects steric fit to the receptor while polarizability effects binding affinity. Excessive buttressing may lower binding affinity. Some variation in these properties through molecular conformational preferences in the biphenyls is thought to explain the apparent 'mixed induction' seen for certain isomers. This is a unifying hypothesis for structural specificity based on the available and definitive crystallographic, theoretical and toxicological data on these pure compounds. PMID- 6257407 TI - Sites of metabolism of N-nitrosodiethylamine in mice. AB - Low-temperature whole-body autoradiography and autoradiography with heated sections in C57Bl mice injected with N-[14C]nitrosodiethylamine showed a homogenously distributed volatile radioactivity in most tissues--indicating an ability of the non-metabolized substance to freely pass the biological membranes and distribute evenly in the intra- and extracellular tissue-water. A high level of non-volatile metabolites was found in several tissues: the nasal and tracheal mucosa, the mucosa of the bronchial tree, the salivary glands, the liver, the mucosa of the oesophagus and the tongue, and the lacrimal glands. Studies in vitro indicated that these tissues had a capacity to degrade N [14C]nitrosodiethylamine (14CO2-production and incorporation of radioactivity in the acid-insoluble material of the tissues were used as indices of the metabolism), whereas several other tissues, which did not accumulate metabolites at short survival intervals in vivo, were devoid of significant metabolic capacity. The relationship between metabolic ability and carcinogenic response of the tissues for N-nitrosodiethylamine is discussed on basis of the obtained results. PMID- 6257408 TI - New syntheses of N-(guanosin-8-yl)-4-aminobiphenyl and its 5'-monophosphate. AB - N-Acetoxy-4-trifluoroacetylaminobiphenyl (N-acetoxy-TFAABP) reacted readily with Guo and GMP at neutrality in a one-step fashion to yield N-(guanosin-8-yl)4 aminobiphenyl (Guo-ABP) (I) and N(guanosin-8-yl)-4-aminobiphenyl-5'-monophosphate (GMP-ABP) (II), respectively. GMP-ABP could also be formed in much lower yield from the reaction of N-acetoxy-4-formylaminobiphenyl (N-acetoxy-FABP) with GMP (pH 7.0) under more rigorous conditions. Enzymatic hydrolysis of GMP-ABP with alkaline phosphatase in Tris buffer (pH 8.0) at 37 degrees C yielded Guo-ABP. Guo ABP showed a brilliant blue fluorescence on exposure to 366 nm UV light and its UV absorption spectrum was identical to that of Guo-ABP prepared by Kriek via a different route. Elemental analysis and nuclear magnetic resonance (NMR) data further confirmed the identity of this compound. PMID- 6257409 TI - Mechanism of action of N2-substituted spin labeled actinomycin D: binding to nucleic acids and erythrocyte ghost membranes. PMID- 6257410 TI - [Paragonimiasis in Black Africa. A recent infection focus in Ivory Coast]. AB - The authors recapitulate in short the distribution of Paragonimiasis in West Africa. They establish and show keys for determination of adults and eggs of the agents of the disease (Paragonimus uterobilateralis, P. africanus, Poikilorchis congolensis). The first intermediate host is unknown but two species of snails are suspected (Afropomus balanoides, Potadoma sanctipauli). A very abundant crab (Liberonautes latidactylus) seems to be the second intermediate host. PMID- 6257411 TI - [1st case of eosinophilic meningitis in Ivory Coat with the presence of a Parastrongylus sp. in the cerebrospinal fluid]. AB - The authors report the first observation, in West Africa, of eosinophilic meningitis in an ivorian child who ingested raw Achatina sp. The presence of a Parastrongylus. sp. in the cerebrospinal fluid was detected. PMID- 6257412 TI - [Do hepatotropic strains of Entamoeba histolytica exist?]. AB - Liver amoebic abscess often occur without any colitic symptoms nor any parasite detection in the colon. The localisation heterogeneity and the experimental data, associated with clinical expression suggest the existence, inside the species E. histolytica, of various strains: non pathogenic one, invasive for the intestine mucous membrane ones and invasive for liver tissue ones. PMID- 6257413 TI - [A case of cylindroma of the lacrimal gland]. PMID- 6257414 TI - [A case of doubtful metastatic tumor enophthalmos]. PMID- 6257415 TI - [Role of a free-living amoeba from water, Acanthamoaba castellani, in the transport of naked or enveloped animal viruses]. AB - The trophozoits of Acanthamoeba castellanii are unable to adsorb poliovirus or vesicular stomatitis Virus. After encystment in medium containing respectively 5.4 x 10(8) and 3 x 10(9) P.F.U./ml cysts did not contain Viruses. These data do not agree with a current hypothesis by which water's free Amoeba could carry animal Viruses. PMID- 6257416 TI - [A thermosensitive inhibitor of the replication of polyomavirus, an extract from BHK2I cells transformed by the Tsa mutant of this virus]. AB - BHK21 cells transformed by wild type or Ts3 mutant polyoma virus contain an inhibitor of polyoma virus replication when grown at permissive (36 degrees C) as well as non-permissive temperature (39 +/- 0.5 degrees C). Cells transformed by the Tsa mutant contain the inhibitor at the permissive but not at the non permissive temperature. The inhibitor reappears in the latter cells however, upon shift from the non-permissive to the permissive temperature. If a reversible protein inhibitor (methionyl-adenylate, reversible inhibitor of the aminoacyl-t RNA synthetase) is applied during the temperature shift experiments, the inhibitor does not reappear indicating that new protein synthesis is required for the recovery of its activity. PMID- 6257417 TI - [Complexes of enkephalins with zinc (II). Study by nuclear magnetic resonance]. AB - Structural modifications of enkephalins obtained by complexation of Zn++ are brought out by high resolution 1 H N M R spectroscopy. For one of the two enkephalins studied, the conformational equilibrium is greatly shifted by the introduction of the metal ion. PMID- 6257418 TI - Role of the intrarenal renin-angiotensin system in the control of renal function. PMID- 6257419 TI - Inhibitory action of adenosine on histamine- and dopamine-stimulated cardiac contractility and adenylate cyclase in guinea pigs. AB - Infusion of adenosine into the coronary arteries of isolated guinea pig hearts produced a dose-dependent inhibition of cardiac contractile force development elicited by bolus injections of histamine (7.5 X 10(-9) mol) or dopamine (1.5 X 10(-8) mol). Threshold concentration of adenosine was 10(-7) M and maximal inhibition (90%) was obtained at 3 X 10(-5) M. Adenosine in the effective concentration range did not alter Ca2+-induced increases in contractile force. The rise in tissue levels of cAMP induced by equieffective doses of histamine (7.5 X 10(-9) mol) and dopamine (1.5 X 10(-8) mol) was inhibited by adenosine (3.5 X 10(-5) M) by about 60%. In a particular membrane preparation of guinea pig ventricles the adenylate cyclase activity stimulated by the histamine (10(-5) M) and dopamine (10(-4) M) was inhibited in a dose-dependent manner by adenosine. This effect could be reversed by theophylline (5 X 10(-5) M) in a competitive manner. The hormone-insensitive adenylate cyclase of a Lubrol-PX solubilized membrane preparation stimulated by NaF or 5'-guanylylimido-diphosphate (GppNHp) was also inhibited by adenosine (40% and 90% inhibition at 10(-5) M and 10(-4) M, respectively). Adenosine did not influence the Km value of the adenylate cyclase for ATP, but markedly lowered Vmax of the enzyme. From additional studies with purine-substituted (N6-methyl-adenosine, N6-phenylisopropyl-adenosine) and ribose substituted (2'-deoxy-adenosine and arabino-furanosyl-adenine) adenosine analogues, we conclude that adenosine may inhibit the inotropic responses to hormones as well as the adenylate cyclase activity by specifically interacting with at least two different sites associated with the adenylate cyclase. PMID- 6257420 TI - Angiotensin-converting enzyme activity and its modulation by oxygen tension in the guinea pig fetal-placental unit. AB - Angiotensin-converting enzyme (ACE) activity in the guinea pig fetal-placental unit was assessed at the different oxygen tensions found in utero, during labor, and at birth. To determine fetal-placental ACE activity, we separately perfused in situ term guinea pig fetuses and their placentas via the umbilical vessels under controlled conditions of flow, temperature, and pH. ACE activity was defined as the percent of angiotensin I (AO) or bradykinin (BK) in Krebs Henseleit solution cleared by a single passage through the placenta or fetus. Peptide concentrations were measured by radioimmunoassay (RIA). Using BK as substrate, we found that placental and fetal ACE activities were reflected by 45% (SD = 10) and 24% (SD = 7) clearances, respectively, at a perfusate PO2 of 29 mm Hg. Maternal hypoxia (PaO2 = 28 mm Hg) decreased placental ACE activity to 16% (SD = 8) and maternal hyperoxia (PaO2 = 191 mm Hg) increased placental ACE activity to 56% (SD = 9). Using a perfusate PO2 of 95 mm Hg, fetal and placental ACE activity increased in less than 5 minutes to 75% (SD = 10) and 77% (SD = 9), respectively. Similar results were obtained using AI as substrate. We conclude that: fetal-placental ACE activity exhibits a chronically reduced level of activity appropriate to the low oxygen tension found in the fetal-placental unit; the placenta is the primary site of ACE activity in the fetus; maternal oxygenation modulates fetal-placental ACE activity; and fetal ACE activity acutely increases with increased fetal oxygenation and thus may play an important physiological role in the regulation of circulating levels of BK and AII and the circulatory adjustments at birth. PMID- 6257421 TI - Age dependence of myocardial Na+-K+-ATPase activity and digitalis intoxication in the dog and guinea pig. AB - Infants and young animals tolerate higher doses of digitalis glycosides, relative to body weight, than adults. One possible explanation for this could be an age dependent difference in the myocardial digitalis receptor, the Na+-K+-ATPase. Two functions of this enzyme were studied in adult, 1- and 6-week-old dogs and guinea pigs: in vitro myocardial uptake of rubidium (86Rb) and binding of ouabain. In guinea pigs, rubidium uptake (pmol Rb/mg LV per 15 min) was: 1 week old: 100.9 +/ 7.1 (mean +/- SE); 6 week: 79.8 +/- 6.7 adult: 55.2 +/- 7.9; (1 week: 6 week: P less than 0.025; 1 week: adult, P less than 0.001; 6 week: adult, P less than 0.025). Similarly in dogs, rubidium uptake was significantly greater at 1 week than at 6 weeks (208 +/- 13 vs. 144 +/- 9; P less than 0.001) and the latter greater than in adults (111 +/- 4) (P less than 0.005). Other groups of anesthetized adult and 6-week-old dogs were given digoxin, 0.3 mg/kg, iv. The young dogs took significantly longer to become cardiotoxic (17.3 +/- 3.4 min vs. 9.3 +/- 1.4 min; P less than 0.025), while their myocardial digoxin uptake was at least as great. Rubidium uptake showed an average decrease of 56% after digoxin but residual uptakes were not different in the two groups. Data for ouabain binding showed similar differences between the various groups of dogs studied. Increased myocardial Na+-K+-ATPase activity, reflected in greater active cation transport and specific enzyme binding, has been demonstrated in young animals and may be partly responsible for their greater tolerance to digitalis glycosides. PMID- 6257423 TI - Oesophagitis--a complication of inhaled steroid therapy. AB - The hazards of steroid therapy, both inhaled and oral, in the asthmatic patient are well recognized. The following case report presents an unusual complication of steroid therapy, namely, that of a concomitant Candida and Herpes simplex oesophagitis occurring in a steroid-dependent 15-year-old asthmatic who had been maintained on inhaled beclomethasone for approximately 15 monts. Oesophagoscopy revealed a 'cottage cheese' appearance of the distal oesophagus. Cultures of the biopsy specimens obtained during oesophagoscopy grew Candida and Herpes simplex virus. Lymphocyte stimulation studies were consistent with a primary cellular response, although the neutralizing antibody titres to the Herpes simplex virus were initially high and remained stable throughout the illness and convalescent period. The patient responded well to oral nystatin therapy and developed no evidence of disseminated herpes. Eleven months after the initial episode, the patient's oropharynx cultured Herpes simplex virus but not Candida. Doctors who care for asthmatic patients need to be aware of the possibility of a herpetic as well as a candidal oesophagitis as a significant complication of inhaled steroid therapy. PMID- 6257422 TI - Pulmonary vasodilator responses to catecholamines and sympathetic nerve stimulation in the cat. Evidence that vascular beta-2 adrenoreceptors are innervated. AB - We investigated the effects of catecholamines and sympathetic nerve stimulation in the feline pulmonary vascular bed under conditions of controlled pulmonary blood flow. Norepinephrine and nerve stimulation caused dose- and stimulus frequency-dependent increases in pulmonary vascular resistance. However, when pulmonary vascular tone was enhanced and alpha receptors blocked, norepinephrine and nerve stimulation caused dose- and frequency-dependent decreases in pulmonary vascular resistance. The decreases in pulmonary vascular resistance were blocked with propranolol and were of greater magnitude than were constrictor responses observed under basal conditions. Vasodilator responses to nerve stimulation were not modified by atropine. Epinephrine and isoproterenol had marked vasodilator activity in the pulmonary vascular bed when pulmonary vascular tone was elevated. When alpha receptors were blocked, isoproterenol and epinephrine had similar vasodilator activity, and when beta receptors were blocked, epinephrine and norepinephrine had marked vasoconstrictor activity. Selective beta-1 receptors antagonists had little effect on vasodilator responses to isoproterenol, whereas responses to this substance were blocked by propranolol. These results suggest that presence of alpha-and beta-2 adrenoreceptors in the feline pulmonary vascular bed and that both types of adrenergic receptors are innervated by the sympathetic nervous system. PMID- 6257424 TI - Potentiation by polymyxin B of the bronchoconstriction following allergen inhalation in patients with atopic asthma. AB - The effect of a single inhalation of allergen on bronchial reactivity to polymyxin B was studied in eight patients with hay fever. In winter the reaction to polymyxin B before and after inhalation of pollen allergen is measured by the FEV. In all patients bronchial reactivity to polymyxin B increased under the influence of allergen. PMID- 6257425 TI - [In vitro and in vivo studies on cytodifferentiation of anterior pituitary cells (author's transl)]. PMID- 6257426 TI - [Evolution of gonadotropin receptor (author's transl)]. PMID- 6257428 TI - [Nuclear triiodothyronine-receptors in rat brain (author's transl)]. PMID- 6257427 TI - [Circadian rhythm of plasma ACTH concentration in healthy young women in Japan and the United States (author's transl)]. PMID- 6257429 TI - [Anterior pituitary LH-RH receptor (author's transl)]. PMID- 6257430 TI - [Anterior pituitary LH-RH receptor (author's transl)]. PMID- 6257431 TI - [A case report of isolated adrenocorticotropic hormone (ACTH) deficiency: a statistical analysis of 32 cases of isolated adrenocorticotropic hormone deficiency reported in Japan (author's transl)]. PMID- 6257432 TI - [Eaton-Lambert syndrome with ADH and ACTH producing lund cancer--a case report (author's transl)]. PMID- 6257434 TI - [The pathology of the peripheral nervous system in two autopsy cases of osteosclerotic myeloma associated with polyneuropathy, skin hyperpigmentation, hypertrichosis and edema (author's transl)]. PMID- 6257433 TI - [Amyloid fibril protein from familial amyloidotic polyneuropathy (author's transl)]. PMID- 6257435 TI - Pitfalls in the diagnosis of rebleeding from intracranial aneurysm. PMID- 6257436 TI - Computed tomography in the diagnosis of subarachnoid haemorrhage and ruptured aneurysm. AB - One hundred consecutive patients with subarachnoid haemorrhage were investigated by computed tomography (CT) within five days of the bleeding. In 19 cases CT indicated other sources than a ruptured aneurysm, most often a cerebellar haematoma. The other 81 patients did not all undergo angiography. It could be estimated by extrapolation that an aneurysm would be demonstrated in 66 of the 68 patients in whom CST showed extravasated blood in the basal cisterns, and in only five of the remaining 13 patients. In a consecutive series of 50 patients with bleeding from a verified aneurysm, CT showed some extravasated blood in all cases and a haematoma in half of these. In 74% the site of the haemorrhage correctly predicted the site of the ruptured aneurysm. Intravenous contrast medium visualized the aneurysm on CT in 15 of 25 cases; this can improve the identification of the bleeding aneurysm to 88%. Rebleeding occurred in 21 patients, and was obvious in Ct in 19. If available, CT should be the first investigation in patients with first and recurrent subarachnoid haemorrhage. PMID- 6257437 TI - Do antifibrinolytic agents prevent rebleeding after rupture of a cerebral aneurysm? A review. PMID- 6257438 TI - Basilar artery occlusion, two angiographically demonstrated cases in young women using oral contraceptives. PMID- 6257439 TI - Role of porta systemic shunt and hepatocellular damage in the genesis of hepatic neuropathy. AB - A study was undertaken to evaluate the relative role of porta-systemic shunts and hepatocellular damage in the genesis of neuropathy in chronic liver disease. Two of the 14 patients with non-alcoholic cirrhosis showed clinical evidence of neuropathy, whereas none of the patients with idiopathic portal fibrosis had evidence of neuropathy clinically. Decreased motor conduction velocities were present in some cases of idiopathic portal fibrosis as well as non-alcoholic cirrhosis. Subclinical evidence of histopathological neuropathy in the form of segmental demyelination and remyelination as well as myelin fiber loss was seen in 10 out of 11 sural nerves studied in idiopathic portal fibrosis group and in all the 10 patients in the non-alcoholic cirrhosis group. No correlation was found between histological features and various parameters studied. It is postulated that the development of clinical or subclinical neuropathy in chronic liver disease depends on two factors, being collateral shunting and hepatocellular damage or both and probably related to abnormalities of nitrogen metabolism. PMID- 6257440 TI - Acro-osteolysis (report of two cases and brief review of literature. AB - Two siblings suffering from acro-osteolysis, a rare disorder, are discussed. Although three distinct types of acro-osteolysis, namely familial, idiopathic, and due to vinyl-chloride, are clearly defined, these patients did not fit into any category. They had intact nails, preserved tactile and sensory system, plantar ulceration and so sensory deficit. Nerve conduction studies showed prolongation of motor distal latencies in median, ulnar, posterior tibial and lateral popliteal nerves. Nerve biopsies from both patients showed severe loss of myelinated fibres of all sizes, but more so of small ones. PMID- 6257441 TI - Pressure neuropathy of the posterior femoral cutaneous nerve. AB - Neuropathy of the posterior femoral cutaneous nerve by compression is described in three cases. The case history and the physical examination are the most important clues to diagnoses. PMID- 6257442 TI - Bone scintigram in cardiac amyloidosis: a case report. AB - Intense, diffuse localization of Tc-99m-pyrophosphate was demonstrated in the right and left ventricles of a patient with biopsy-proved amyloidosis and severe congestive heart failure. This finding is strong presumptive evidence of myocardial infiltration by amyloid in the presence of biopsy-proven amyloidosis elsewhere in the body. PMID- 6257443 TI - Progression of clinical signs in severe infant botulism. Therapeutic implications. AB - The clinical evaluation of nine patients with severe infant botulism revealed an identifiable progression of signs due to blockade of the cholinergic synapse similar to that described for competitive blocking agents. This predictable sequence reflects different "margins of safety" for muscles involved in repetitive activities, diaphragmatic function and movement of the extremities. It is important for the clinician to realize that return of peripheral motor activity does not signify a completely recovered cholinergic synapse. Instead of having a four- to five-fold margin of safety, the infant remains close to the point of neuromuscular blockade. Added insults or stress to neuromuscular transmission may precipitate respiratory failure. An understanding of the signs associated with progressive impairment of cholinergic synapses both during onset and during resolution of disease will allow safe care of the infant and will diminish the risk of iatrogenic complications. Evaluation of head control is the most sensitive physical finding indicative of return of adequate neuromuscular function and signifies that oral feedings can be reinstituted. PMID- 6257445 TI - [Therapeutic use of a new vasoactive drug in cerebral vascular diseases in elderly patients]. PMID- 6257444 TI - Regulation of norepinephrine release by peripheral alpha 2-receptor stimulation. AB - Although extensive evidence obtained in animals and in vitro supports the existence of an alpha-receptor-mediated inhibitory regulation of norepinephrine release, the importance of such a system in man is not established. Norepinephrine release was physiologically stimulated by change of posture and dynamic exercise in subjects while they were infused with phenylephrine, a predominant alpha 1-receptor agonist, alpha-methylnorepinephrine, a predominant alpha 2-agonist, and saline. Agonist infusions were administered both at rates that induced a slight elevation in supine systolic pressure and at nonpressor rates. Agonist concentrations that induced much the same pressor responses (alpha 1) were assumed on the basis of in vitro experiments to differ substantially in their affinity for alpha 2-receptors. The hemodynamic response and the increase of plasma norepinephrine induced by changes in posture and exercise were of the same order during infusions of alpha-methylnorepinephrine, phenylephrine, and saline. Similar results from the "nonpressor" as from "pressor" agonist infusions suggested that baroreflex-induced reduction in sympathetic neuronal activity had not confounded the results. Correction of plasma concentrations for individual values of norepinephrine clearance provided an index of norepinephrine release into the circulation that was not changed by phenylephrine or alpha methylnorepinephrine. These results raise the question of the importance of peripheral alpha 2-receptors in the regulation of norepinephrine release in man. PMID- 6257446 TI - [Neurohumoral influences on the digestive system: studies of the digestive trophic and metabolic effects]. PMID- 6257447 TI - Computation of decompression schedules for single inert gas-oxygen dives using a hand-held programmable calculator. AB - An algorithm for on-site computation with a hand-held programmable calculator (TI 59, Texas Instruments) of single inert-gas decompression schedules is described. This program is based on Workman's 'M-value' method. It can compute decompression schedules with changes in the oxygen content of the breathing mixture and extension of stay at any decompression stop. The features of the program that enable calculation of atypical dive profiles, along with the portability of small calculators, would make such an algorithm suitable for on-site applications. However, since dive profiles generated by the program have not yet been tested, divers are warned not to generate schedules until their safety has been established by field tests. PMID- 6257448 TI - Age dependent biochemical changes in dermal connective tissue. Relationship to histological and ultrastructural observations. AB - A biochemical study of skin biopsies of young normal subjects and two groups of aged subjects, one active and the other confined to bed, was made and the results compared with histological observations. Skin biopsies were incubated with 3H proline and 14C glucosamine and connective tissue components were sequentially extracted. In each extract the specific activity of total and collagenous protein was determined. With age a decrease was observed in both the amount of protein and the 3H proline incorporation of collagenous extracts. A parallel increase in 14C glucosamine incorporation was also noticed in extracts containing glycosaminoglycans and structural proteins. These results agree in part with the changes observed by light and electron microscopy, which revealed an increase in ground substance and fragmentation of collagen bundles in the dermis of older subjects. PMID- 6257449 TI - Response of pregnant mares to equine herpesvirus 1 (EHV1). AB - Twenty-one pregnant mares were inoculated with EHV1. Nineteen became infected as evidenced by clinical signs and/or viremia but only one mare aborted a virus infected fetus. The viremias were leukocyte-associated and appeared to be non productive, latent infections of these cells. Infectivity, detectable by cocultivation, persisted in the circulating leukocytes for as long as 9 days without resulting in abortion. The data suggest that it is extremely difficult to evaluate the efficacy of vaccines in preventing EHV1 (Rhinopneumonitis) abortion due to the paucity of non-exposed mares, lack of tests which measure residual protection, and an incomplete understanding of the pathogenic mechanisms involved in abortion due to this virus. PMID- 6257450 TI - Univalent antibody fragments as tools for the analysis of cell interactions in Dictyostelium. PMID- 6257451 TI - The bovine genes for phosphoglycerate kinase, glucose-6-phosphate dehydrogenase, alpha-galactosidase, and hypoxanthine phosphoribosyltransferase are linked to the X chromosome in cattle-mouse cell hybrids. AB - Bovine embryonic trachea cells were hybridized with mouse A9 cells deficient in hypoxanthine phosphoribosyltransferase, and cattle-mouse hybrid cells clones were isolated after HAT/ouabain selection. In these interspecific cell hybrids, bovine glucose-6-phosphate dehydrogenase, alpha-galactosidase, and phosphoglycerate kinase were expressed concordantly with bovine HPRT. Their expression depended on the presence of bovine X chromosome. These data indicated that the genes for G6PD, PGK, and HPRT are linked and can be assigned to the bovine X chromosome. PMID- 6257452 TI - Acute respiratory failure secondary to polymyxin-B inhalation. AB - A patient with asthma was given aerosol treatment with a solution containing 25 mg of polymyxin-B, and 0.7 ml of isoetherine diluted in 2 ml of isotonic saline. After a few inhalations, he had a severe, near-fatal asthmatic reaction requiring resuscitation, intubation, and mechanical ventilation. The reaction was attributed to the polymyxin-B and occurred despite the patient's receiving maintenance prednisone, 80 mg per day, and the concomitant administration of isoetherine. Possible mechanisms include: (1) bronchial irritant effect or reflex bronchoconstriction, (2) type I (IgE mediated) allergic reaction, or (3) direct histamine release induced by polymyxin, a basic polypeptide known to cause histamine release. PMID- 6257453 TI - Pathogenesis of trachoma. PMID- 6257454 TI - Vitamin D metabolism in patients treated with phenytoin and phenobarbitone. AB - There are many reports of abnormalities in calcium metabolism and even of frank osteomalacia in patients taking anticonvulsant drugs. Although enzyme induction has been suggested to be the cause of increased requirements for vitamin D leading to these changes, this has still to be proved. We have studied the metabolism of [3H]cholecalciferol and 25-hydroxycholecalciferol in subjects taking anticonvulsant drugs. The rate of removal of cholecalciferol from the plasma was no different from that in control subjects and no abnormality was detected in the production of disappearance of 25-hydroxycholecalciferol. However, plasma concentrations of 25-hydroxycholecalciferol fell more rapidly during the winter in epileptic subjects than in control subjects. Our results do not confirm that these changes are due to enzyme induction. PMID- 6257455 TI - Chemical disease in humans: problems in comparative toxicology. AB - Difficulties in assessment of the comparative pharmacology of drugs now apply to the effects on humans of foreign compounds from the environment (xenobiotics). Perhaps the most striking change in perspective has been the recognition that a latency of several decades may precede the development of toxic effects. Xenobiotics may persist and accumulate in tissue stores, and estimates of biologically active doses are sometimes complicated by the presence of highly toxic trace contaminants and homologues that have varying biological activity. The effects of chemical exposure on the tissues may be obscured by the absence of the pathognomonic symptoms normally associated with the structural changes of disease. Interactions between two or more xenobiotics or between xenobiotics and genetic and metabolic variables may explain the lack of coherence between carefully defined laboratory observations and the clinical effects of enzyme inducing xenobiotics. Since we have considerable evidence that biological processes are strikingly similar in different mammalian species, the toxicological significance to humans of enzyme induction and related processes requires careful evaluation. PMID- 6257456 TI - Cytomegalic inclusion disease diagnosed endoscopically. AB - Two patients who received renal transplants developed erosions or ulcers in the upper gastrointestinal tract. In both cases endoscopic evaluation enabled a diagnosis of cytomegalovirus (CMV) infection to be made quickly and safely. We emphasize the importance of early diagnosis of CMV infection and how endoscopy may be helpful. PMID- 6257457 TI - The effect of dietary fiber on glucose and hormone responses to a mixed meal in normal subjects and in diabetic subjects with and without autonomic neuropathy. AB - We investigated the effects of fiber on responses of blood glucose, serum insulin, gastric inhibitory polypeptide (GIP), and immunoreactive pancreatic glucagon (IRG) to ingestion of mixed meal with and without added fiber (5 g guar and 5 g pectin) in 12 normal, healthy subjects and in 12 age-, sex-, and weight matched non-insulin-dependent, maturity-onset diabetic subjects (NIDDM). Fiber markedly enhanced glucose tolerance in the normal subjects without a change in insulin or GIP but with a significant reduction in glucagon responses. Fiber also markedly improved glucose tolerance in the NIDDMs without changing insulin or GIP but with a significant reduction in the glucagon responses. The NIDDMs were divided into two groups of six subjects, with and without autonomic neuropathy (AN). In NIDDMs without AN, glucose tolerance was improved by fiber without a change in insulin, IRG, or GIP. In diabetic subjects with AN, glucose tolerance was not improved, although glucagon levels were lowered and insulin and GIP responses were unchanged. It appears, therefore, that fiber improves glucose tolerance by altering factors other than insulin. It seems also that autonomic nervous supply to the gastrointestinal tract is important in mediating the effect. PMID- 6257459 TI - Nesidioblastosis, islet cell hyperplasia, and adenomatosis in a case of metastasizing insulinoma: contribution to the genesis of the islets of Langerhans. AB - An unusual case of insulinoma is described in a 40-yr-old woman whose resected pancreas showed multiple adenomas with lymph node metastasis, associated hyperplasia of islets, and nesidioblastosis. The association of nesidioblastosis with this continuum of proliferative changes adds further evidence for a ductular origin of islet cell tumors. PMID- 6257458 TI - The effect of bran on glucose kinetics and plasma insulin in non-insulin dependent diabetes mellitus. AB - Experiments were carried out on two groups of diabetic patients treated (1) by diet alone (group A) and (2) by diet and oral agents (group B), the latter being discontinued 3 days before each test. All patients were tested twice. To measure rates of glucose metabolism, 3H-3-glucose was infused before and during a standard 3-h 50-g oral glucose tolerance test. 14C-1-glucose was added to the glucose solution and the percentage of ingested glucose that appeared in peripheral blood was calculated. Bran improved glucose tolerance only in group B patients by delaying the peripheral appearance of ingested glucose but had no effect on glucose absorption in group A. In contrast, patients in group A showed a marked reduction in their insulin response when bran was mixed with the glucose. Despite this reduction, glucose tolerance, the metabolic clearance rate (MCR) of glucose, and all other rates measured were unaffected by bran. Thus we conclude that in patients adequately controlled by diet alone, the effect of insulin was potentiated when bran was ingested, but the mechanism involved remains obscure. PMID- 6257460 TI - [Effect of tetraethylammonium on the electrically and mechanically excitable channels of Pacinian corpuscles]. PMID- 6257461 TI - [Gene mutation induction in mammalian cells by a temperature-sensitive SV 40 mutant]. PMID- 6257462 TI - [Mechanism of action of vitamin PP and nicotinamide nucleotides on neuromuscular transmission in guinea pig taenia coli]. PMID- 6257463 TI - [Reliability of enzymatic cell protection against superoxide radicals and aging]. PMID- 6257464 TI - [Dispersion analysis of conductivity fluctuations in electrically excitable membranes]. PMID- 6257465 TI - [Symmetrical sodium pump model]. PMID- 6257466 TI - [Calcitonin as a marker for bronchial carcinoma (author's transl)]. AB - Calcitonin levels were determined in the serum of 126 patients with lung tumours of various histological types before the onset of treatment. High hormone levels were found in 54% of patients with small cell carcinoma and in 17% of patients with squamous cell carcinoma. There was no correlation with the degree of spread of the disease. However, serial determinations of calcitonin before and during cytostatic treatment showed good correlation between hormone levels and the clinical course. Response to treatment led to an equivalent fall in serum calcitonin. A clinically recognisable relapse was preceeded by a rise in calcitonin by 1-2 months. PMID- 6257467 TI - [Captopril in the treatment of essential hypertension (author's transl)]. AB - The antihypertensive effect of captopril was tested on 19 patients with essential hypertension, WHO grade I or II. In 11 patients blood pressure levels returned to normal over an observation period of 12 weeks at a dose of 3 C 50-150 mg daily (group A). In eight patients with grade II hypertension the absolute blood pressure reduction was the same, but did not reach normal levels (group B). Although additional intake of propranolol, at a dose of 3 X 40 mg daily, achieved further reduction, normal pressures were still not attained. Initial blood pressure levels were higher and plasma-renin activity lower in patients of group B than of group A. There was a definite rise in plasma-renin activity with captopril, but corresponding to the suppression of plasma-renin in severe hypertension it was less. There was a fall in plasma-aldosterone levels, corresponding to a reduced angiotensin II level as a result of inhibition of the converting enzyme. The fall in plasma-aldosterone activity was less in severe hypertension, although there was the same inhibition of converting enzyme activity in both groups. Normochromic anaemia was noted in three patients, requiring further observation and explanation. No patient developed orthostatic hypotension or reflex tachycardia. PMID- 6257468 TI - [Changes in antibody titre after rubella vaccination in primarily rubella-sera positive parturient women. Demonstration of antigen-specific (rubella) and non specific stimulated antibody titres (author's transl)]. PMID- 6257469 TI - [Fanconi syndrome in an adult coincident with early myeloma with monoclonal IgG, type kappa, anomaly (author's transl)]. AB - First description of a case of early myeloma with monoclonal IgG, type kappa, anomaly plus Bence-Jones proteinuria and Fanconi's syndrome in a 67-year-old woman. Characteristic crystalline inclusion bodies were found in plasma cells of bone marrow and renal tissue. PMID- 6257470 TI - [Distribution of bovine coronavirus infection in selected areas of Germany: detection of antibodies by microimmunodiffusion and neutralization (author's transl)]. PMID- 6257471 TI - [Review of the occurrence of Aujeszky's disease virus in the Rhineland in special reference to the years 1976-1979 (author's transl)]. PMID- 6257472 TI - [Bovine leucosis: actual daily control of running and reading the ID-test by using a test-system in routine-examinations (author's transl)]. PMID- 6257473 TI - Effects of malnutrition and quipazine on rat cerebral cortex ATPase activity during development. AB - Previous results suggested a possible association between brain serotonin (5-HT) and Na+-K+-ATPase, in vivo. We extended the study to the developmental response of this enzyme to early 5-HT changes induced by early malnutrition and by a serotonin agonist. Agonist treatment produced a response of the enzyme activity at early stages of development in normal and malnourished brains. The induction of 5-HT changes through malnutrition could be playing an important role in the development and maturation of Na+-K+-ATPase activity, and brain 5-HT receptors could possibly be involved in such a response. PMID- 6257474 TI - [Ultrastructural mechanisms of transendothelial transport in blood vessels]. AB - The author describes a series of structural aspects of transendotheliumiumial transport on the basis of literary data, printed in journals and coming from well known foreign laboratories. He reports data on three types of endothelium- uninterrupted, fenestrated and interrupted. He indicates the ways of transfer of lipid-soluble substances and ultrastructural devices for transfer of water and water-soluble substances. These devices are divided into two groups-universal (vesicular structures, intercellular slits), which are characteristic of the three types of endothel and specific (fenestra and pores), characteristic of fenestrated and interrupted endothel respectively. The author presents a series of actual questions about vesicular transport-nature and movement of micropinocytotic vesicules, structure, permeability and orientation of transendothelial canals. He describes data on possibility of intercellular slits as sites for passive transport of water and water-soluble substances. He indicates distribution and structure of binding complexes between endothelial cells, limiting permeability of intercellular contacts. The structure and permeability of fenestra and pores are presented as sites of passive transport, but those of the pores-for active passage of cellular elements as well. Various ultrastructures, connected with endothelial permeability, are surveyed as morphologic equivalents of the small or large pores by the physiological theory of pores. PMID- 6257475 TI - [Effect of a protein hydrolysate on enzymatic activity in the aorta wall in experimental atherosclerosis]. AB - Kirk, Antonini, Weber and others have found that the activity of the specific phosphomonoesterase 5-nucleotidase is lowered. In the present study, carried out on male guinea pigs and fed with cholesterol for a period of 150 days, the authors discovered analogous change in 5-nucleotidase activity of the aortic wall. Administration of protein hydrolysate induced a statistically significant increase of the enzymic activity in the aorta of animals, fed with cholesterol. The combined treatment with protein hydrolysate and vitamins caused even more significant activation of the enzyme. The established changes in the activity of 5-nucleotidase were similar to the changes in the activity of adenylpyrophosphatase of animals under the same experimental conditions. PMID- 6257476 TI - [Determination of adenylate kinase (AK) phenotypes in blood stains]. AB - The author examined blood spots, prepared experimentally with known types of the enzyme adenyl kinase (AK) 1-1 and 2-1 on the most frequently met in the practice materials-carriers: cloth, paper, wood, knife, glass and stone. The studies were performed by means of electrophoresis on cellulose acetate folio. She found that the types of AK could well be determined with spot duration of 5-6 months, saturating the material (cloth, paper), and over 1 year in the presence of crusts of dried blood, regardless of the material-carrier (including cloth and paper). She recommends that the system AK should be introduced in the practice during examination of blood spots at experts' reports according to material evidences. In view of phenotype frequencies of AK in our country the theoretical probability for two blood spots, randomly taken, to differ only by AK is 12.85%. PMID- 6257477 TI - [Determination of adenylate kinase (AK) enzymatic types in cadaveric and stored blood]. AB - The author examined 243 samples of corpse blood with various duration and causes of death. In all cases she found the types of AK even in corpses with advanced decomposition and date of death since 1 month, 2 months, but in one corpse-since 3,5 months. In Blood, stored at room temperature, she found with certainty, the types of AK up to 6 weeks, but in some cases even over 10 weeks, which showed stability of this enzyme. PMID- 6257478 TI - [Acute alcoholic polyneuropathies as an unusual clinical and electromyographic entity]. AB - The clinical and EMG aspects of a particular form of polyneuropathy encountered in seven young alcoholics are presented. This form is characterized by an acute, severe and extensive paralysis with motor, sensitive and vegetative deficit. The reasons of the sudden aggravation of a previous chronic PN are thiamine deficiency -- wich realise the BERI-BERI with Wernicke-Korsakoff encephalopathy - and a probable poisoning due to the multiples toxics included in the alcoholised beverages. The remarkable clinical features of this PN are: the quickness of the onset, the extension and the severity of the paralysis, the young age of the patients and the relative prevalence of the women -- these two points suggesting a possible congenital predisposition -- and the fast improvement under vitamino therapy and abstinence. Our EMG findings, in accord with some recent electro physiological studies with histological confrontations, show up the indirect signs of a massive axonal degeneration in contrast to a mild demyelination. The EMG examen was a good contribution to exclude other possibilities like Guillain Barre syndrome or alcoholic myopathy, and to follow the evolution. PMID- 6257479 TI - In vitro effect of TRH on adenylate cyclase and cAMP in rat anterior pituitary and on TSH and PRL release into incubation medium. AB - Rat anterior pituitaries were incubated for 20 min with 1, 5 or 20 nmol TRH ml-1 and cAMP was measured in the homogenate of pituitary tissue after incubation, while TSH and PRL release into the medium was estimated with the aid of specific radioimmunoassay. In a similar experiment the activity of adenylate cyclase in pituitary homogenates was measured after the incubation with 0.5, 1.0 or 5.0 nmol TRH ml-1. Significant increase of TSH and PRL in the medium was found after 5 and 20 nmol TRH ml-1, while cAMP was significantly increased after 20 nmol TRH ml-1 only. The activity of adenylate cyclase was significantly increased after all doses of TRH used. In general, these findings are consistent with current views on the effect of hypothalamic hormones via adenylate cyclase - cAMP system and show that the responsiveness and sensitivity of an in vitro system using whole pituitaries appears to be less that of in vivo system. PMID- 6257481 TI - Studies on the mode of action of calciferol. XXIX. Biochemical characterization of 1,25-dihydroxyvitamin D3 receptors in chick pancreas and kidney cytosol. PMID- 6257480 TI - Bone collagen synthesis in vitro: structure/activity relations among parathyroid hormone fragments and analogs. AB - The structural requirements for the inhibition of net bone collagen synthesis by parathyroid hormone (PTH) in vitro have been examined by study of the effects of selected fragments and analogs of bovine PTH (bPTH) upon the incorporation of [3H]proline into collagenase-digestible and -nondigestible proteins by neonatal mouse calvarial bone in organ culture. At concentrations of 10(-10)-10(-7) M, the amino-terminal fragment bPTH-(1-34) was found to be as potent as intact bPTH in the specific suppression of net bone collagen synthesis after 24 h in culture. The synthetic fragments bPTH-(1-30), bPTH-(1-28), and bPTH-(3-34) were approximately 3%, 1%, and 0.2% as active, respectively, as bPTH-(1-34), in good agreement with previous estimates of the relative potencies of these hormonal fragments on bone resorption in vitro and in vivo and on adenylate cyclase activation in and receptor binding to isolated renal membranes. The amino terminal analog [Ser1]bPTH-(1-34) displayed no reduction in biological activity compared with bPTH-(1-34), as previously found for bone resorption in vivo. The overall results with this assay system indicate a minimum sequence for biological activity that extends from residues 3-28 of intact bPTH, which is consistent with similar estimates in other test systems and emphasizes the importance of the aminoterminus of the hormone in the expression of its biological effects on bone formation as well as resorption. Moreover, these findings support the potential usefulness of the mouse calvarial culture system in predicting the skeletal activity in vivo of new synthetic analogs of PTH. PMID- 6257482 TI - Regional differences in the molecular weight profiles of corticotropin and alpha melanotropin the hypothalamus. PMID- 6257483 TI - Regulation of responsiveness of cultured adrenal cells to adrenocorticotropin and prostaglandin E1: cell density, cell division, and inhibitors of protein synthesis. AB - In cultured bovine adrenocortical cells, responsiveness to ACTH, as assessed by the maximal rate of ACTH-stimulated cAMP production, has been found to depend on cell density and cell proliferation, while the maximal rate of prostaglandin E1 (PGE1)-stimulated cAMP production was constant. The combination of low cell density and normal cell proliferation caused a specific decline in responsiveness to ACTH. Responsiveness did not decline at any density when proliferation was inhibited by mitomycin C treatment. Specific declines in responsiveness to ACTH were also seen when cultures were treated with cycloheximide or sodium butyrate. When protein synthesis was completely inhibited by cycloheximide treatment, responsiveness to ACTH declined with a half-life of 20.5 h and responsiveness to PGE1 declined with a half-life of 75h. Because PGE1-stimulated cAMP production indicates intact adenylate cyclase catalytic activity, changes in ACTH-stimulated cAMP production appear to be due to specific changes in functional ACTH receptors. PMID- 6257484 TI - Naloxone, adrenalectomy, and steroid replacement: evidence against a role for circulating beta-endorphin in food intake. AB - Naloxone has a dose-dependent, significant anorectic effect when administered to normal rats, consistent with an antagonism of central or peripheral enkephalinergic or endorphinergic mechanisms. Mean levels of circulating immunoreactive beta-endorphin were similar in intact rats (0.5 ng/ml) and dexamethasone-treated adrenalectomized rats (0.5 ng/ml). In contrast, plasma levels were high in adrenalectomized rats with no replacement steroid (1.3 ng/ml) and in adrenalectomized rats given the mineralocorticoid deoxycorticosterone (0.9 ng/ml). In sharp distinction to the clear changes in circulating immunoreactive beta-endorphin produced by adrenalectomy and selective steroid replacement, no differences were seen in baseline food intake or anorectic response to naloxone. We conclude that a physiological role for circulating beta-endorphin in the regulation of food intake appears unlikely. PMID- 6257486 TI - Activation of adenosine 3',5'-monophosphate-dependent protein kinase in normal and malignant bone cells by parathyroid hormone, prostaglandin E2, and prostacyclin. AB - Hormonal activation of cAMP-dependent protein kinase has been studied in cultured cells derived from a rat osteogenic sarcoma and in osteoblast-rich cells grown from newborn rat calvaria. Both cell strains contain adenylate cyclase activities which respond to parathyroid hormone (PTH) and a variety of prostanoids. PTH, prostaglandin E2 (PGE2), and prostacyclin (PGI2) were all capable of activating cAMP-dependent protein kinase(s) in suspensions of the two cell types. Activation was very rapid in all cases, being detectable at 10 sec and maximal between 30-60 sec. Using saturating concentrations of hormones, the protein kinase activity ratio remained elevated (between 0.6-0.9) for up to 35 min after the start of PGE2 stimulation, but declined toward basal activity ratio 5-10 min after stimulation with PTH or PGI2. Each of the hormones caused a dose-dependent increase in activation of cAMP-dependent protein kinase in both cell types. Half maximal activation of the enzyme occurred at 2 X 10(-9) M bovine PTH for calvarial cells, at 10(-8) M bPTH for osteogenic sarcoma cells, and at 2-4 X 10( 8) M PGE2 and 1-3 X 10(-7) M PGI2 for both cell types. Maximal activation of protein kinase occurred before maximal cAMP accumulated, implying that only a fraction of cAMP is biologically significant. These two cell strains provide a useful means of analyzing postreceptor events in the hormonal regulation of bone cells. PMID- 6257485 TI - Mechanism of thyroid hormone inhibition of thyrotropin-releasing hormone action. AB - The addition of thyroid hormone to cultures of GH3 or GH4C1 pituitary tumor cells maintained in medium with hypothyroid serum decreased the concentration of specific receptors for TRH. The relationship between thyroid hormone effects on TRH receptors and TRH responses was examined by testing the concentration dependence, time course, and specificity of these changes. The concentrations of T3 giving half-maximal decreases in [3H]TRH binding and inhibition of the PRL response to TRH were 0.20 and 0.24 nM, respectively. TRH stimulated the rate of [3H]uridine uptake by 50% in cultures incubated without added T3 but did not increase [3H]uridine uptake in cells incubated with thyroid hormone. The PRL response to TRH was substantially inhibited 12 h after the addition of T3, and the uridine uptake response was completely blocked in 8 h. Two other stimuli of PRL secretion, sodium butyrate and isobutylmethylxanthine, were effective in the presence or absence of T3. Thyroid hormone did not reduce the specific binding of either [125I-Tyr1]somatostatin or [125I]iodoepidermal growth factor. Somatostatin decreased the secretion of GH and PRL by pituitary tumor cells grown with or without T3. The data show that the effects of thyroid hormones on TRH receptors are specific and suggest that regulation of receptor concentrations may be the direct cause of thyroid hormone regulation of pituitary responsiveness to TRH. PMID- 6257487 TI - Interaction of age and thyroid hormone status on Na+-K+ ATPase in rat renal cortex and liver. AB - Na+-K+ ATPase was measured in euthyroid, hypothyroid, and hyperthyroid rats aged 6 weeks, 6 months, and 20-24 months. There was a small but significant decline in basal enzyme activity with increasing age in renal cortical tissue. Enzyme activity decreased with hypothyroidism and increased with hyperthyroidism. With increasing age, both the magnitude of the increase resulting from thyrotoxicosis and the absolute enzyme level were significantly less with each increase in the age of the experimental animals. Hypothyroid animals displayed no age-related decline in renal cortical Na+-K+ ATPase. The decline in Na+-K+ ATPase in renal cortical tissue is thyroid hormone dependent. In addition, age modifies the response of Na+-K+ ATPase to thyroid hormone. PMID- 6257488 TI - Regulation of the rat thyrotropin receptor in vitro. AB - After our recent finding that the TSH receptor of the rat is regulated by endogenous TSH, we studied the system further by investigations in vitro. After exposure of the tissue to TSH, thyroid lobes showed decreased responsiveness to stimulation by the hormone when cAMP accumulation was measured as an end-point. This state of refractoriness was correlated with a decrease in hormone binding, the nature of which was mainly a loss of receptor sites when data were subjected to Scatchard analysis. Dissociation of bound TSH by washing the membrane preparation with NaCl revealed that occupation of the receptor could be responsible for part of the apparent down-regulatory effect after 14 h of exposure to TSH, whereas after 24 h of exposure, a true decrease in receptor sites prevailed. PMID- 6257489 TI - Changes in ovarian LHRH receptor content during the onset of puberty in the female rat. AB - LHRH and some of its analogs have been reported to exert inhibitory effects on ovarian function, seemingly following interaction of the neurohormone with specific, high affinity binding sites. The present experiments were undertaken to determine whether LHRH binding sites in the ovary undergo quantitative changes during the onset of puberty in the rat. Changes in LHRH receptor content were assessed by the binding of the stable LHRH analog, [D-Ala6, Pro9]-LHRH to ovarian membrane preparations. LHRH binding in prepubertal rats (anestrus, A) was 166 +/- 11 fmol/mg protein, declined gradually (to 127 +/- 14 fmol/mg protein) during the early proestrous (EP) phase of puberty--a time at which intrauterine fluid begins to accumulate and uterine weight increases more rapidly--and became even lower (75 +/- 4 fmol/mg protein) by 1300 h of the day of first proestrus (LP), prior to the initiation of the first gonadotropin surge. At the time of the surge (1600 h) binding was 70 +/- 3 fmol/mg protein. LHRH binding was minimal on the day of the first estrus (E) and increased slightly on diestrus (D). The results indicate that the ovarian steroidogenic activation that precedes the first surge of gonadotrophins in the rat is associated with a marked loss in ovarian LHRH receptor content and suggest that a reduction in LHRH inhibitory function within the ovary may be a contributing factor to the pubertal enhancement in ovarian secretory activity. PMID- 6257490 TI - Androgens decrease LHRH binding sites in rat anterior pituitary cells in culture. AB - [125I]-[D-Ser(TBU)6]LHRH-EA binds to a single class of high affinity sites in rat anterior pituitary cells in culture at an apparent dissociation constant of 0.25 nM at 0-4C. The order of potency of a representative group of LHRH agonists and antagonists to displace the labeled ligand is similar to their LH-releasing activity. Treatment of pituitary cells for 48 h with 100 nM 5 alpha dihydrotestosterone leads to a 40% decrease of the number of LHRH receptors with no change of binding affinity. This loss of LHRH receptors is accompanied by a similar decrease of the LH responsiveness to LHRH, thus providing the first evidence for a direct effect of sex steroids on pituitary LHRH receptors as a possible mechanism of feedback action. PMID- 6257491 TI - Gonadotropin-induced positive regulation of testicular luteinizing hormone receptors. PMID- 6257492 TI - Characterization of several clonal lines of cultured Leydig tumor cells: gonadotropin receptors and steroidogenic responses. AB - Several clonal lines of cultured Leydig tumor cells have been established and characterized in terms of gonadotropin receptors and steroid production. Although freshly isolated cells derived from the M5480P tumor have functional hCG receptors, only two of the five clonal lines established were shown to bind significant quantities of hCG. In these clones, steroid production can be stimulated to the same extent by hCG, cholera toxin, and 8-Br-cAMP. The other three clones bind a small amount of hCG and respond to the hormone with a marginal increase in steroidogenesis. Steroid production, however, is significantly stimulated by cholera toxin or 8-Br-cAMP. A comparison of the steroids produced by freshly isolated cells and two of the clones revealed some changes in the steroidogenic pathway. The most obvious change is an increase in the ability of the cultured cells to synthesize 20 alpha-dihydroprogesterone (20 alpha-hydroxypregn-4-en-3-one). These clonal lines may provide a suitable model system for the study of gonadotropin actions and regulation of the expression of differentiated functions of Leydig cells. PMID- 6257493 TI - In vitro stimulation of 25-hydroxycholecalciferol 1 alpha-hydroxylation by parathyroid hormone in chick kidney slices: evidence for a role for adenosine 3',5'-monophosphate. AB - We studied the effect of parathyroid hormone (PTH) on the in vitro conversion of 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] by kidney slices from vitamin D-deficient chicks. Bovine PTH (bPTH) stimulated 1,25 (OH)2D3 production at low concentrations, with maximal stimulation (65%) at a concentration of 25 ng/ml bPTH in the absence of theophylline. Higher concentrations of bPTH resulted in less stimulation. The addition of 5 mM theophylline to the incubation buffer decreased basal 1,25-(OH)2D3 production but potentiated the stimulation of 1,25-(OH)2D3 production by PTH. Maximal stimulation (170%) was observed with 2 ng/ml bPTH in the presence of theophylline. Maximal stimulation of cAMP production by the kidney slices required 2- to 3-fold larger concentrations of bPTH. However, cAMP by itself stimulated 1,25-(OH)2D3 production, with maximal stimulation (70%) at 10(-7)-10( 5) M cAMP. We conclude that stimulation by PTH of 1,25-(OH)2D3 production can be potentiated by theophylline and mimicked by cAMP. However, such stimulation occurs at PTH concentrations lower than that required for optimal stimulation of adenylate cyclase activity. PMID- 6257495 TI - 1,25-dihydroxyvitamin D3 and malignant melanoma: the presence of receptors and inhibition of cell growth in culture. AB - In this study we demonstrate the presence of specific, high-affinity receptors for 1,25-dihydroxyvitamin D3 in malignant melanoma. Receptors are present both in cultured melanoma cells and in melanoma tumor tissue produced by inoculation of cells into athymic rats. The receptor sediments at 3.25 on sucrose density gradients, possesses a preferential affinity for 1,25-(OH)2D3 and has an apparent Kd of 0.18 nM by Scatchard analysis. We also demonstrate that human melanoma cells are responsive to 1,25-(OH)2D3 in vitro. Inclusion of 1,25-(OH)2D3 in the culture medium produced a marked increase in cell doubling time. This inhibitory effect of the hormone on melanoma cell proliferation was dose-related and represents the first demonstration of a 1,25-(OH)2D3 mediated action on tumor cells. PMID- 6257494 TI - Thyroid hormone regulation of rat heart, lymphocyte, and lung beta-adrenergic receptors. AB - In the rat, exogenous hyperthyroidism is associated with increased myocardial beta-adrenergic receptors. In man, however, despite the hyperadrenergic manifestations of thyrotoxicosis, lymphocyte beta-adrenergic receptors are unaltered. To test the hypothesis that lymphocytes do not reflect changes in myocardial beta-adrenergic receptors with hyperthyroidism, we characterized and quantified lymphocyte, myocardial, and lung (as another marker tissue) beta adrenergic receptors in T3-treated rats. In T3-treated rats (500 microgram T3/kg.day for 3 days), myocardial beta-adrenergic receptors, as measured by [3H]dihydroalprenolol binding, increased by 60% over controls. In contrast, lymphocyte and lung beta-adrenergic receptors were unaltered. However, while lymphocyte adenylate cyclase activity was also unaltered with T3 treatment, lung adenylate cyclase activity was increased. Our data demonstrate that in rats, as in humans, hyperthyroidism is not associated with an increase in lymphocyte beta adrenergic receptors. The differences in lymphocyte and myocardial receptors and lymphocyte and lung adenylate cyclases suggest that the response to T3 is a tissue-specific phenomenon. The data also suggest that despite the lack of increase in lymphocyte beta-adrenergic receptors in human hyperthyroidism, myocardial beta-adrenergic receptors may be increased. PMID- 6257496 TI - Enhanced calmodulin-dependent (Ca2+ + Mg2+)-ATPase of hypothyroid rat erythrocyte membranes. PMID- 6257497 TI - des-Ser2 salmon calcitonin: a biologically potent synthetic analog. AB - We studied the biological activity of a synthetic analog of salmon calcitonin (SCT), from which the serine2 residue within the amino-terminal disulfide ring had been omitted (des-Ser2-SCT). This analog proved to be indistinguishable from SCT with respect to hypocalcemic activity in vivo, displacement of [125I]SCT from rat renal membranes, and accumulation of cAMP in incubated renal cortical slices, des-Ser2SCT was twice as potent as SCT with respect to adenylate cyclase activation in renal membranes. Since the deletion did not impair biological activity, it appears that the function of the intact ring structure does not critically depend on its encompassed peptide chain length. PMID- 6257498 TI - Gonadotropin-releasing hormone surge: possible modulation through postsynaptic alpha-adrenoreceptors and two pharmacologically distinct dopamine receptors. PMID- 6257499 TI - Regulation of pituitary gonadotropin-releasing hormone receptors by gonadal hormones. PMID- 6257500 TI - Studies on cholesterol esterase in the rat adrenal. AB - We have investigated the characteristics and properties of cholesterol esterase (CEase) in the rat adrenal to clarify the mechanism of synthesis of free cholesterol from esterified cholesterol. CEase activity was estimated using substrate vesicles which were sonicated mixtures of cholesteryl oleate and phosphatidylcholine (PC). CEase showed two optima at around pH 4.5 and pH 8.25. The acid CEase was found mainly in the lysosomal fraction, and the alkaline CEase was found mainly in the microsomal fraction. Both acid and alkaline CEase activities were markedly enhanced by increasing the concentration of PC, but not by phospholipids. The activities were not increased by the addition of cAMP, ATP, and MgCl2, when the molar ratio of cholesteryl oleate to PC was 1:0.2, but were increased when the molar ratio was 1:2. Thus, it is suggested that free cholesterol for steroidogenesis may be supplied by two different organelles (lysosome and microsome), and that the composition of the substrate complex, such as the ratio of esterified cholesterol to phospholipids, may play a crucial role in the regulation of adrenal CEase. Increases in both acid and alkaline CEase activities were observed in adrenal homogenates prepared from hypophysectomized rats treated with an iv injection of ACTH when the molar ratio of cholesteryl oleate to PC used as a substrate vesicle was 1:0.2, but not when the ratio was 1:2. Therefore, the present observation indicate that activation of CEase by ACTH is dependent on the substrate state, especially that of the cholesterol ester droplet in vivo. PMID- 6257501 TI - Mechanism by which 17 beta-estradiol inhibits ovarian androgen production in the rat. AB - The mechanism by which 17 beta-estradiol inhibits ovarian androgen biosynthesis was investigated. Immature 25-day-old rats were treated for 2 days with estradiol, after which whole ovaries were dispersed, and gonadotropin binding and cAMP and steroid hormone production were examined. When dispersed cells from untreated control ovaries were incubated with hCG (100 ng/ml), there were marked increases (10-fold) in steroid production, with the major steroids being progesterone and androstenedione. The stimulation of steroidogenesis by hCG was dose-related (ED50 = 100 pg/ml hCG). After 2 days of estradiol treatment, the maximum hCG stimulation of androstenedione, testosterone, 17 alpha hydroxypregnenolone, and 17 alpha-hydroxyprogesterone production by ovarian cells was inhibited by 90%; pregnenolone production was unchanged, while progesterone production was increased by 30%. Time course studies showed that the stimulatory effect of hCG on androgen production was maximally inhibited (90%) after 12 h of estradiol treatment. Implanting miniestradiol capsules unilaterally under the ovarian bursa caused a 77% decrease in the hCG stimulation of androgen production by the estradiol-treated cells, while progesterone production was unchanged. hCG stimulated steroidogenesis in the contralateral ovary was not altered. Estradiol treatment did not affect the binding capacity, the hCG stimulation of cAMP production, or the number of steroid-producing cells in the ovaries. It is concluded from these experiments that exogenous estradiol acts directly on the rat ovary to abolish the hCG stimulation of androgen production by rapidly inhibiting 17 alpha-hydroxylation. PMID- 6257502 TI - Glucocorticoid regulation of myocardial beta-adrenergic receptors. AB - One action of glucocorticoids is to enhance the tropic effect of catecholamines on heart muscle. To test the hypothesis that this action of glucocorticoids is mediated by modulation of beta-adrenergic receptors, we characterized and quantified myocardial beta-adrenergic receptors in adrenalectomized and glucocorticoid-replaced rats. Adrenalectomy was associated with an increase in myocardial beta-adrenergic receptors, as measured by [3H]dihydroalprenolol binding (P less than 0.001). This increase occurred by 6 h, with no difference over time to 7 days. The administration of cortisol (80 mg/kg.day) to adrenalectomized rats prevented the increase in beta-adrenergic receptors (P less than 0.01). The data indicate that glucocorticoids modulate myocardial beta adrenergic receptors. However, these results do not support the hypothesis that glucocorticoid enhancement of catecholamine action is mediated by these changes, suggesting that glucocorticoids exert this action at a level other than the beta adrenergic receptor site. PMID- 6257503 TI - High molecular weight forms of immunoreactive ACTH in a human pituitary and ectopic ACTH-producing tumors. AB - High molecular weight forms of immunoreactive ACTH (IR-ACTH) were studied in a human pituitary gland and 4 ectopic ACTH-producing tumors in man. Both the pituitary and tumor extracts contained "big" IR-ACTH, which eluted near the void volume, and a small amount of "intermediate" IR-ACTH components, which eluted between the void volume and 125I-alpha h1-39 ACTH, in addition to "little" ACTH which coeluted with 125I-alpha h1-39ACTH by Sephadex G-100 gel filtration. A significant amount of the "big" IR-ACTH applied bound to the concanavalin A agarose column and was eluted with 0.2 M alpha-methyl-D-mannopyranoside, indicating the glycoprotein content of "big" IR-ACTH fractions. When the "big" and "intermediate" fractions were further analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis, they were resolved into 4 molecular forms of IR-ACTH with apparent molecular weight of 37,000, 24,000 , 18,000 and 4,500, respectively. These results indicate that 3 high molecular forms of IR-ACTH are present in the human pituitary and the ectopic ACTH-producing tumors. PMID- 6257505 TI - Quantitative analysis of the proton and charge stoichiometry of cytochrome c oxidase from beef heart reconstituted into phospholipid vesicles. AB - The proton and charge stoichiometry of cytochrome c oxidase reconstituted into phospholipid vesicles has been analysed using a fast responding oxygen electrode and a system for the simultaneous measurement of H+, K+ or lipophilic cations, and O2. From initial rate measurements after addition of reductant (ascorbate /N,N,N',N'-tetramethyl-p-phenylenediamine) the following stoichiometries could be extrapolated: K+/e-, between 1.85 and 2.05, H+/e-, between 0.58 and 0.75. Lipophilic cations can replace valinomycin/potassium as the charge . compensating system. Net H+ extrusion was observed for up to 11 turnovers of the enzyme (11 O2/cytochrome aa3). The variation of the internal pH buffering capacity of the vesicles has an influence on the number of turnovers during which net proton translocation can be observed, but has no influence on the determined stoichiometries. PMID- 6257504 TI - PBB inhibits metabolic cooperation in Chinese hamster cells in vitro: its potential as a tumor promoter. AB - Using an in vitro assay system, polybrominated biphenyl (PBB) was assessed for its ability to inhibit metabolic cooperation between 6-thioguanine sensitive and resistant Chinese hamster V79 cells. Using a nonlethal range of the chemical, PBB was shown to inhibit metabolic cooperation (a form of cell-cell communication) in a manner similar to other known tumor promoters. Results suggest that PBB could act, epigenetically, as a teratogen and a carcinogenic promoter. PMID- 6257506 TI - Isolation and partial characterization of the plasma membrane of purified bovine neutrophils. AB - 1. Large amounts of granulocytes can be isolated from bovine blood by differential centrifugation and hypotonic lysis of erythrocytes, followed by separation of neutrophils and eosinophils by centrifugation through a gradient of colloidal silica. 2. Careful homogenization of the purified neutrophils and subfractionation of the postnuclear supernatant by centrifugation through a discontinuous sucrose gradient provides a membrane fraction (at the 20/32%, w/w, sucrose interface), which collects about 20--35% of the activity of plasma membrane marker enzymes. 3. Treatment of the plasma membrane fraction with 0.5 M KCl removes some protein and activity of granule enzymes, leading to an about 20- 35-fold enrichment in specific activity of plasma membrane marker enzymes. In particular, there is a 25-fold enrichment in a Ca2+-dependent ATPase, whose half maximal reaction velocity is reached at 2.2 X 10(-7) M Ca2+. 4. High-resolution sodium dodecyl sulphate/polyacrylamide gel electrophoresis reveals a complex composition of the neutrophil plasma membrane, with about 40 polypeptides stained by Coomassie blue. Ten of these peptides are more intensely stained by the dye; their apparent molecular weight ranges from 81 000 to 34 000. All these ten polypeptides but one (which is likely to be actin) are markedly enriched in the plasma membrane fraction over the original homogenate. 5. Since bovine blood can be obtained in unlimited amounts, the procedures here described can be applied to a large-scale purification of the neutrophil plasma membrane, suitable for biochemical studies. PMID- 6257507 TI - Synthesis of threonine dehydratase in neonatal rat liver. AB - Antiserum against rat threonine dehydratase has been raised in rabbits. The rate of incorporation of [3H]leucine into threonine dehydratase was found to increase dramatically after birth. Actinomycin D suppressed the rate of the synthesis of the enzyme in the postnatal rat liver, although the antibiotic was without effect on the incorporation of leucine into total cytosolic protein. The administration of dibutyryl-adenosine 3',5'-monophosphate to foetal rats in utero or postnatal rats resulted in a marked enhancement of the rates of synthesis of threonine dehydratase. PMID- 6257508 TI - Molecular cloning of bovine thyroglobulin complementary DNA. Characterization of 2500-base-pair and 1900-base-pair fragments. AB - Double-stranded thyroglobulin complementary DNA (cDNA) was synthesized from purified 33-S bovine thyroglobulin mRNA. This synthetic structural gene has previously been shown to contain three sites for the restriction endonuclease HindIII, yielding two internal fragments of 1900 and 2500 base pairs respectively. Recombinant molecules were prepared by ligating the HindIII restricted cDNA to the plasmid pBR322 which had been linearized by the same enzyme. When Escherichia coli was transformed with this mixture, it yielded two kinds of colonies each harboring recombinant plasmids containing one of the two cDNA fragments. Both recombinant molecules hybridized specifically to translatable thyroglobulin mRNA. Sequence homology between the two cloned DNAs could not be detected by cross-hybridization experiments; this argues against the existence of internal structural repetition in thyroglobulin subunits. Together, the two cloned DNA fragments represent 55% of the 8000-base-pair double-stranded thyroglobulin DNA. PMID- 6257509 TI - A histone-specific acetyltransferase is associated with simian-virus-40 chromatin. AB - [14C]Thymidine-labeled simian virus 40 nucleoprotein complexes were prepared from nuclei of lytically infected African green monkey kidney cells. The nucleoprotein complexes were further purified by sucrose gradient centrifugation and then incubated in the presence of [3H]acetyl-coenzyme A. We observed a transfer of [3H]acetyl groups to the endogenous histones H2B, H3 and H4. The enzyme was solubilized in the presence of 0.5 M NaCl and showed properties described for the DNA-binding acetyltransferase (J. Bohm, E. J. Schlaeger and R. Knippers, preceding paper in this journal). PMID- 6257510 TI - Characterization of cloned complementary DNA covering more than 6000 nucleotides (97%) of avian vitellogenin mRNA. AB - The messenger RNA coding for chicken vitellogenin, a precursor of the egg-yolk proteins lipovitellin and phosvitin, is synthesized in the liver following estrogen injection. This mRNA is 6600 nucleotides long. We have previously reported the cloning and preliminary characterization of some cDNA fragments representing portions of the vitellogenin mRNA [Biochem. Biophys. Acta, 606, 34- 46 (1980)]. In this paper we report the full characterization of a larger series of such clones, representing almost the entire length of the mRNA, by restriction endonuclease mapping, R-loop mapping, RNA-DNA hybridization and by translation in vitro of the RNA which hybridizes to the cloned DNA. From the results we conclude that the chicken vitellogenin mRNA, unlike that of Xenopus laevis, does not vary in sequence over most of its length, although some variations in the cDNA sequences were detected particularly in clones derived from the 3' terminus of the RNA. All sequence variants appear to be present in RNA prepared from single animals. The possible origins of these minor species are discussed. Furthermore, we describe a cDNA clone complementary to an mRNA which is about the same size as vitellogenin mRNA and which codes for an egg yolk protein antigenically related to lipovitellin. This mRNA is synthesized constitutively. PMID- 6257511 TI - Structural studies on two high-mobility-group proteins from calf thymus, HMG-14 and HMG-20 (ubiquitin), and their interaction with DNA. AB - High mobility group (HMG) protein 14, which, like HMG-17, has been implicated in the structure of 'active chromatin' is shown by 270-MHz NMR and by circular dichroism to be in a disordered conformation in free solution. At low ionic strength protein HMG-14 binds to DNA by weak attachment of the N-terminal half of the molecule and is released by 0.3 M NaCl, the ionic strength at which the protein is extracted from chromatin. The protein HMG-20 (ubiquitin), a constituent of the conjugate protein A 24, is shown to be a highly stable compact globular protein that remains folded over a pH range of 1--13 and has a half denaturation temperature of 85 degrees C when thermally denatured. Circular dichroism indicates 28% helix and 12% beta sheet. Despite having 15% basic residues it binds only very weakly to DNA. A detailed study of the folding of ubiquitin has been made by a combination of several NMR approaches, including decoupling, nuclear Overhauser enhancement and titration. Several line assignments have been made and it is shown that, although the tyrosine and histidine are buried residues, they are not adjacent to one another nor are they close to either of the phenylalanines, of which at least one is also a buried residue. PMID- 6257512 TI - Studies of the conformational behaviour and preferential interactions with opiate receptors of the cis and trans forms of [Dmet2,pro5]enkephalin and [Dmet2,pro5]enkephalinamide by 1H and 13C NMR, theoretical calculations and 13C relaxation measurements. PMID- 6257513 TI - The role of Ca2+ and cyclic AMP in the phosphorylation of rat-liver soluble proteins by endogenous protein kinases. AB - Rat liver soluble proteins were phosphorylated by endogenous protein kinase with [gamma-32P]ATP. Proteins were separated in dodecyl sulphate slab gels and detected with the aid of autoradiography. The relative role of cAMP-dependent, cAMP-independent and Ca2+-activated protein kinases in the phosphorylation of soluble proteins was investigated. Heat-stable inhibitor of cAMP-dependent protein kinase inhibits nearly completed the phosphorylation of seven proteins, including L-type pyruvate kinase. The phosphorylation of eight proteins is not influenced by protein kinase inhibitor. The phosphorylation of six proteins, including phosphorylase, is partially inhibited by protein kinase inhibitor. These results indicate that phosphoproteins of rat liver can be subdivided into three groups: phosphoproteins that are phosphorylated by (a) cAMP-dependent protein kinase or (b) cAMP-independent protein kinase; (c) phosphoproteins in which both cAMP-dependent and cAMP-independent protein kinase play a role in the phosphorylation. The relative phosphorylation rate of substrates for cAMP dependent protein kinase is about 15-fold the phosphorylation rate of substrates for cAMP-independent protein kinase. The Km for ATP of cAMP-dependent protein kinase and phosphorylase kinase is 8 microM and 38 microM, respectively. Ca2+ in the micromolare range stimulates the phosphorylation of (a) phosphorylase, (b) a protein with molecular weight of 130 000 and (c) a protein with molecular weight of 15 000. The phosphate incorporation into a protein with molecular weight of 115 000 is inhibited by Ca2+. Phosphorylation of phosphorylase and the 15 000-Mr protein in the presence of 100 microM Ca2+ could be completely inhibited by trifluoperazine. It can be concluded that calmodulin is involved in the phosphorylation of at least two soluble proteins. No evidence for Ca2+-stimulated phosphorylation of subunits of glycolytic or gluconeogenic enzymes, including pyruvate kinase, was found. This indicates that it is unlikely that direct phosphorylation by Ca2+-dependent protein kinases is involved in the stimulation of gluconeogenesis by hormones that act through a cAMP-independent, Ca2+ dependent mechanism. PMID- 6257514 TI - 'Swell dialysis' demonstrates that adenylate cyclase in Trypanosoma brucei is regulated by calcium ions. AB - A new technique, 'swell dialysis', is described that allows the study of cellular enzymes in situ if they are located in the cytoplasm or on the cytoplasmic face of any membrane. The technique is potentially applicable to any population of individual eukaryotic cells that lack a cell wall. In this study swell dialysis has been applied to an examination of the regulation of adenylate cyclase in blood-stream forms of Trypanosoma brucei (427-12/ICI-060). Adenylate cyclase in this protozoon is shown to be controlled by Ca2+. There is a 16-fold stimulation of the cyclase at 100 microM Ca2+ over basal activity without added Ca2+. The ability of Ca2+ to stimulate adenylate cyclase is lost upon rupture of the cell, which is reminiscent of the loss of control of the adenylate cyclase in Escherichia coli by sugars of the phosphotransferase system when cell breakage occurs. The physiological function of the Ca2+ activation of adenylate cyclase in T. brucei has not been established but a possible role in the change of surface coat in bloodstream forms should be considered. PMID- 6257515 TI - Complex fucolipids of hog gastric mucosa. Structure of the ceramide eikosahexoside. AB - The structure of a complex fucolipid from hog gastric mucosa containing twenty sugar residues and exhibiting blood-group (A + H) activity has been investigated. Based on the results of immunological assays, partial acid hydrolysis, sequential degradation with specific exoglycosidases, oxidation with periodate and chromium trioxide, and permethylation analysis, we suggest that the carbohydrate chain of this fucolipid contains four termini. One of the termini bears beta Gal1 leads to 4 beta GlcNAc disaccharide, two bear blood-group A determinant and one bears H determinant. Two of the branches, terminated by beta Gal1 leads to 4 beta GlcNAc and blood-group A determinant, and two terminated by blood-group A and H determinants, are linked through beta Gal1 leads to 4 beta GlcNAc1 leads to 3/6 and beta Gal1 leads to 4 beta GlcNAc1 leads to 4 beta GlcNAc1 leads to 3/6 to the galactose residue adjacent to glucosylceramide core. PMID- 6257516 TI - Opening of potassium channels in Escherichia coli membranes by thiol reagents and recovery of potassium tightness. AB - The retention of high potassium levels in Escherichia coli is not dependent on intact energy metabolism, since without the presence of a carbon source or in the presence of energy inhibitors significant K+ gradients can be maintained. In contrast, with 0.5 mM N-ethylmaleimide, K+ depletion is immediate and complete. As a final result, intracellular K+ is approximately three times more concentrated than the K+ in the medium. Increase of K+ in the medium is immediately followed by K+ uptake whereas in the unpoisoned state only an increase in the osmotic pressure of the medium would result in an increase of the K+ pool. The intracellular K+ undergoes continuous turnover in the poisoned cells whereas in intact cells turnover is strictly dependent on the presence of a metabolizable carbon source. After removal of the thiol reagent the cell recovers its capacity to concentrate potassium. The recovery process is inhibited by energy inhibitors or by incubation at low temperature but not by chloramphenicol. It is only slightly slowed down by carbon or sulfur starvation. The leak provoked by N-ethylmaleimide is similar in wild-type E. coli cells when a derepressed kdp uptake system working in the micromolar range of the K+ concentration is responsible for the intracellular pool of K+ and when, in a medium millimolar K+ concentration range, the trkA and trkD systems are predominant. PMID- 6257517 TI - Partial purification and differential androgen sensitivity of protein phosphokinases from nuclei of rat ventral prostate. PMID- 6257519 TI - The subcellular distribution of cytidine 5'-monophosphosialic acid synthetase in rat liver. PMID- 6257520 TI - Coexistence of nucleosomal and various non-nucleosomal chromatin configurations in cells infected with herpes simplex virus. AB - Coexistence of four different forms of chromatin was observed by electron microscopy in nuclear spread preparations of monkey kidney cells during late stages of infection with herpes simplex virus (HSV-1 AMG). Besides typical nucleosomal (i) chromatin, thin (3-5 nm) strands morphologically indistinguishable from protein-free DNA were frequent, without (ii) or with (iii) sparse 10-22 nm large granules different from nucleosomes. In addition, uniformly thick (mean 17 nm), heavily stained chromatin strands (iv) were seen. The non nucleosomal character of types (iii) and (iv) chromatin was also demonstrated by their resistance to histone removal in Sarkosyl and heparin. All four forms were seen in capsid-associated HSV-DNA molecules, and various combinations of these forms occurred in adjacent regions of the same DNA molecule, including the vicinity of replication branch points. Especially frequent were regions of chromatin types (ii) or (iii) alternating with thickly coated intercepts of type (iv) chromatin, the latter often displaying "bubble"-like strand separations. The appearance of chromatin types (ii)-(iv) was dependent on viral replication. These chromatin arrays were compared with structures observed in purified HSV-DNA from these cells. Patterns of single-stranded regions were found in HSV-DNA that were similar to those observed in the thickly coated type (iv) chromatin. It is concluded that, in these nuclei, non-nucleosomal arrangements can be formed, at least on viral DNA, under conditions of continued DNA synthesis and inhibited protein synthesis, and that single-stranded DNA is packed into a characteristic thick strand of non-nucleosomal chromatin by association with a special, probably virus-coded protein. PMID- 6257518 TI - Ca2+-binding proteins in nuclei. AB - Nuclei isolated from skeletal muscle of 15-day-old chick embryos, adult chickens, rabbits and from rat liver contain on the average 8-18 nmol Ca2+/mg protein. Digestion of nuclei with DNAase I and RNAase at 37 degrees C for 8--12 h reduced the Ca2+ binding by more than 90%. After nuclease treatment, Ca2+-binding proteins were identified in the nonhistone chromosomal protein fractions and in the insoluble residue by equilibrium dialysis and centrifuge transport, in media of 0.1 M KCl and 1 mM MgCl2. The interaction of Ca2+-binding proteins with chromatin may be of importance in the regulation of the gene expression in response to changes in cytoplasmic and nucleoplasmic free-Ca2+ concentration. PMID- 6257521 TI - A computer-assisted method for semi-quantitative assessment of salivary gland diseases. AB - The authors report on a computer-assisted method that allows a semi-quantitative assessment of salivary gland function under normal and pathologic conditions. They illustrate some mathematical procedures suitable for this purpose and the results achieved in various salivary gland diseases. PMID- 6257522 TI - Quantitation of thyroidal binding of iodide by compartmental analysis verified by an intravenous perchlorate discharge test. AB - Compartmental analysis was applied to 123I-iodide uptake data to quantitate iodine binding in the human thyroid gland. The method allowed for arterio/venous differences in plasma tracer level and for an "instantaneous" phase of thyroid uptake. Results were checked by an intravenous perchlorate discharge test. Observations in eleven normal and untreated thyrotoxic subjects confirmed earlier findings that iodine binding takes place rapidly, the binding rate constant being much greater than the exit rate constant. A lower limit of 0.15 min-1 for the binding rate constant in the uninhibited gland was estimated from the observations in one subject who demonstrated a small perchlorate discharge. The method was used in the study of eight subjects with an intrinsic binding defect and of twenty-four thyrotoxic subjects being treated with 5 mg or 20 mg carbimazole, twice daily. Binding rate constants (range 0.003--0.105 min-1) were typically less than the exit rate constants (range 0.027--0.156 min-1), the net clearance of iodide ranging from 1.5 to 67.9% of the unidirectioinal clearance, compared to 72% in the uninhibited gland. The method proved useful in assessing the severity of an intrinsic binding defect and in the investigation of lack of response to antithyroid drug therapy. PMID- 6257523 TI - The effect of parathyroid hormone on technetium-99m pyrophosphate distribution in rats. AB - Sprague-Dawley rats were treated with varying quantities of parathyroid hormone for 1--3 days, then sacrificed at periods ranging from 1--6 h after administration of 99mTc-pyrophosphate. Very little increase in bone accumulation of tracer occurred with this treatment. A small, but obvious decrease occurred in the blood levels of 99mTc-pyrophosphate and a smaller and less consistent decrease was affected in the muscle levels of the radiopharmaceutical. The overall result was an improvement in the bone/blood and bone/muscle ratios. It is suggested that the basis of the "supernormal" bone scan of hyperparathyroidism is achieved by this mechanism and that the increased bone uptake of other ions in response to parathyroid hormone is not shared by 99mTc-pyrophosphate. PMID- 6257524 TI - Effects of parathyroid hormone and calcitonin on plasma and nephrogenous cyclic adenosine-3',5'-monophosphate in normal subjects and in pathological conditions. AB - To evaluate the response of bone cells and kidney to parathyroid hormone (PTH) and calcitonin (CT), the acute effects of these hormones given intravenously on plasma cyclic adenosine 3',5'-monophosphate (cAMP), nephrogenous cAMP and clearance ratio (cAMP:creatinine), have been studied in normal subjects and in patients with Paget's disease, hypoparathyroidism and osteopetrosis. Twenty-five subjects were given bovine synthetic PTH, thirty-eight calcitonin (sixteen salmon, eighteen human and four porcine CT). In normal subjects and in patients with Paget's disease and hypoparathyroidism plasma cAMP increased within 1 h following PTH intravenous infusion. The same dose of PTH failed to produce any increase in plasma cAMP level in two children with marble bone disease. Nephrogenous cAMP increased in all cases. A different relative potency of calcitonins in increasing plasma cAMP has been observed in normal subjects, according to previous results on the plasma calcium lowering effect. Paget's disease patients showed a greater increase in plasma cAMP following infusion than normal subjects. The measurement of nephrogenous cAMP and the clearance ratio (cAMP: creatinine) demonstrated a minor involvement of the kidney in the production of cAMP after CT infusion; the late increase observed in nephrogenous cAMP was probably due to a parathyroid rebound following the hypocalcemic effect of CT. PMID- 6257525 TI - Cellular mechanisms of restricted immunoglobulin formation in the human neonate. AB - The functional capacity of human neonatal B lymphocytes has been investigated by in vitro methods using T lymphocyte-dependent (pokeweek mitogen, PWM) and independent (Epstein-Barr virus, EBV) polyclonal B cell activators. B cell activation of single cells was detected by class-specific immunoglobulin (Ig) secretion using a reversed hemolytic plaque assay. It was found that neonatal B cells were triggered to secretion of IgM by EBV, with a magnitude comparable to adult levels, but that, in contrast to B cells from adults, they did not secret IgG. Cord lymphocytes did not secret Ig although they displayed a sizable DNA synthetic response to PWM. Using cell separation and culture experiments, it was shown that (allogeneic) adult T lymphocytes could restore cord B cell responsiveness to PWM and that cord T lymphocytes could not cooperate with adult B cells. In addition to this immaturity of cord T helper function for antibody synthesis, we found cells in the cord T cell-enriched fraction which inhibited the polyclonal response of adult lymphocytes to both PWM and EBV. These lymphocytes suppressed adult B lymphocytes directly but appeared ineffective against neonatal B lymphocytes themselves. The nature of these suppressing cells and their possible role in the fetal/maternal relationship are a matter of speculation. PMID- 6257526 TI - Increased benzodiazepine receptor number elicited in vitro by a novel purine, EMD 28422. AB - EMD 28422 (N6-[2-(4-chlorophenyl)-bicyclo-2.2.2.octyl-(3)]-adenosine) was demonstrated to increase the number of binding sites for [3H]diazepam (Bmax) in vitro without an accompanying increase in receptor affinity (KD). The increase in receptor number was observed in both crude synaptosomal preparations (P2) and thrice-washed membrane preparations with and without the addition of 50 microM GABA. Furthermore, this effect appeared to be independent of the concentration of chloride ion, since the increases in Bmax were observed in both Tris-HCl and Tris maleate buffer. The effects of EMD 28422 were stereospecifically antagonized by the GABA antagonist bicuculline, despite the lack of effect of EMD 28422 on [3H]muscimol binding at concentrations which markedly increased benzodiazepine receptor number. Neither EMD 39011 nor adenosine, the two parent moieties of EMD 28422, increased [3H]diazepam binding at concentrations of up to 1 mM. The increases in benzodiazepine receptor number observed with EMD 28422 in vitro suggests that this compound induces a conformational change in the benzodiazepine receptor which may cause the dissociation of an endogenous noncompetitive inhibitor of [3H]diazepam binding from the membrane, thus 'unmasking' binding sites. The stereospecific antagonism of this effect by bicuculline and the apparent inability of GABA to alter the action of EMD 28422 suggests the presence of a novel type or different functional state of GABA receptor which may play a permissive role in the rapid modulation of benzodiazepine receptor number in vitro. PMID- 6257527 TI - Presynaptically acting catecholamines bind to alpha 2-adrenoceptors labelled by 3H-clonidine. AB - It is known that certain catecholamine congeners can decelerate the heart rate by inhibiting the prejunctional sympathetic neurones to the atrium. The present study was done to determine whether this presynaptic action might be associated with either dopamine receptors or alpha-adrenergic receptors. The effects of 10 catecholamine congeners wee tested on the specific binding of 0.2 nM 3H-WB-4101 and 0.2 nM 3H-clonidine to calf frontal cortex homogenates, and that of 2 nM 3H apomorphine to calf caudate nucleus homogenates. The drugs tested were apomorphine, the aminotetralin M-7, 3 dialkylated dopamine congeners, and 5 congeners of octahydrobenzo(f)-quinoline. The IC50 values (concentrations for 50% inhibition of binding) ranged from 400 to 28,000 nM for 3H-WB-4101, from 3 to 270 nM for 3H-apomorphine, and from 9 to 1000 nM for 3H-clonidine. Only the IC50 values for 3H-clonidine binding correlated with the in vitro IC50 values for inhibiting atrial acceleration (data from Long et al., 1975, 1979). These findings suggest that 3H-clonidine appears to bind to the same site in brain (alpha 2-adrenoceptor) on which catecholaminergic drugs act to produce cardiodeceleration. PMID- 6257528 TI - Effect of VIP, phenoxybenzamine and prednisolone on cyclic nucleotide content of isolated guinea-pig lung and trachea. AB - Vasoactive intestinal polypeptide (VIP) increased the cyclic AMP content of guinea pig lung and tracheal tissues. Combinations of the peptide with prednisolone or with phenoxybenzamine potentiated the effect of VIP on cyclic AMP. The trachea-relaxant effect of VIP also was reinforced by the addition of prednisolone or phenoxybenzamine. At the same time, cyclic GMP content in these tissues changed little in response to these agents. The results provide a biochemical basis for the tracheal-relaxant action of these agents, and for the potentiation of bronchodilation by prednisolone and by alpha-receptor blockade. The findings are also consistent with the view that relaxation of airway smooth muscle is mediated by an elevation of intracellular cyclic AMP. PMID- 6257529 TI - Dissociation of cyclic AMP and contractile responses to isoprenaline: effects of a dihydropyridine derivative, nicardipine (YC-93), on canine ventricular muscle. AB - Nicardipine (YC-93), a 1,4-dihydropyridine derivative, inhibited the cyclic AMP phosphodiesterase (PDE) activity of purified PDE in a cell-free preparation. Its inhibitory action on the purified PDE was about seven times that of papaverine. On the other hand, YC-93 did not affect the intracellular cyclic AMP level and the accumulation of cyclic AMP caused by isoprenaline in the isolated canine right ventricular myocardium. YC-93 caused a prominent negative inotropic action which developed gradually to reach a steady level 1 h after its administration. The potency of YC-93 to depress the force of contraction was one tenth that of D600. The dose-response curve for isoprenaline was shifted to the right and downward in the presence of YC-93 in a concentration-dependent manner, and the positive inotropic action of calcium was also inhibited markedly by YC-93. The depressant action of YC-93 on the positive inotropic actions of isoprenaline and calcium was more prominent than that of D600. Although YC-93 is a potent PDE inhibitor in the cell-free preparation, the PDE in the intact cell system may be not accessible to the drug. Thus, it is considered that YC-93 acted as a calcium antagonistic drug on the isolated canine ventricular myocardium, and thereby inhibited the positive inotropic action of isoprenaline without affecting the intracellular accumulation of cyclic AMP caused by isoprenaline. PMID- 6257530 TI - Effect of colchicine on jejunal adenylate cyclase activity, PGE2 and cAMP contents. AB - The effect of colchicine on jejunal adenylate cyclase activity, prostaglandin E2 (PGE2) and cAMP contents, the enzyme and mediators involved in intestinal fluid secretion was tested in rats. Four h after the intraperitoneal injection of colchicine (0.5 mg/100 g body wt.) mucosal PGE2 content, adenylate cyclase activity and mucosal cAMP content were almost doubled. Pretreatment with indomethacin (4 mg/kg body wt., s.c./day x 2) or methyl prednisolone (3.0 mg/kg body wt.) decreased both the increase in mucosal PGE2 content and the stimulation of adenylate cyclase activity induced by colchicine. These results suggest that the stimulation of adenylate cyclase activity and an increase in mucosal PGE2 and cAMP contents might be among the mechanisms whereby colchicine induces a net accumulation of water manifested clinically as diarrhea. It is also suggested that the stimulation of adenylate cyclase activity is mediated by the increase in mucosal PGE2 content. PMID- 6257531 TI - Down regulation of dihydroalprenolol and imipramine binding sites in brain of rats repeatedly treated with imipramine. AB - In rats receiving repeated injections of imipramine, there is a reduction in the number of high affinity binding sites for [3H]imipramine and [3H]dihydroalprenolol present in crude synaptic membrane preparations from various brain structures. The location of the sites that become subsensitive to the two ligands did not coincide; the binding sites to [3H]imipramine became subsensitive in the hippocampus but not in cortex or cerebellum. In contrast the binding sites to [3H]dihydroalprenolol became subsensitive in cortex and cerebellum but not in hippocampus. It can be suggested that in rats repeatedly treated with imipramine the down regulation of beta-adrenergic receptors may not coincide with the down regulation of the high affinity binding sites for imipramine. Such a dissociation is supported further by experiments with rats treated with iprinidol. PMID- 6257532 TI - Inhibition of nerve-mediated contractions in isolated guinea-pig ileum by 1 methylisoguanosine, a novel purine from a sponge. AB - 1-Methylisoguanosine, a novel purine isolated from the sponge Tedania digitata (Schmidt) selectively inhibited contractions produced by nerve stimulation in the guinea-pig ileum but was without effect on contractions produced by acetylcholine or histamine. The ED50 for inhibition of nicotine responses or responses to submaximal transmural stimulation was 1.1 mumoles/l. The inhibition of nerve mediated contractions appeared to be due to inhibition of transmitter release from nerve endings in the ileum, as has been suggested for the action of adenosine. Theophylline antagonized the action of 1-methylisoguanosine and overall the results suggest that 1-methyl-isoguanosine acts at an adenosine receptor in the guinea-pig ileum, but is approximately ten times more potent than adenosine itself. A series of related purines which were resistant to the action of adenosine deaminase were also tested for their effect on the nerve-mediated contractions of guinea-pig ileum and the results compared with the in vivo effect on muscle relaxation in mice. All active purines tested produced results qualitatively similar to those of 1-methylisoguanosine itself. PMID- 6257533 TI - mu- and delta-opiate receptors: correlation with high and low affinity opiate binding sites. PMID- 6257534 TI - Ethanol enhances [3H]diazepam binding at the benzodiazepine-GABA-receptor ionophore complex. PMID- 6257535 TI - The differences in purine metabolism between T and B lymphocytes. AB - In this study enzyme activities involved in purine metabolism were measured in T and B lymphocytes separated by E and EAC rosetting methods. Adenosine deaminase, purine nucleoside phosphorylase and HGPRTase activities were significantly elevated in T cells, compared to the activities in B cells. There were no significant differences in adenosine kinase and APRTase activities between T and B lymphocytes. In contrast, PRPPsynthetase activities were higher in B cells than in T cells. The uptake of various radiolabeled precursors by mitogen stimulated lymphocytes was studied. The uptake of 14C-formate by the mitogen stimulated lymphocytes was markedly lower, compared to that of 14C-adenosine and or 14C purine bases. The uptake of 14C-adenosine by PHA stimulated lymphocytes was considerably higher than that of Con A or PWM stimulated lymphocytes. However, the uptake of 14C-hypoxanthine into lymphocytes stimulated with PWM was increased by comparison with unstimulated lymphocytes. From these results it seems that adenosine plays a central role in the metabolism of T cells, and that purine bases are preferentially utilized in B cells. PMID- 6257536 TI - Effects of enkephalin, morphine, and naloxone on the electrical activity of the in vitro hippocampal slice preparation. PMID- 6257537 TI - Neoaplectana carpocapsae: Nematode accumulations on chemical and bacterial gradients. PMID- 6257538 TI - Plasmodium berghei: modification of sialic acid on red cells from infected mouse blood. PMID- 6257539 TI - Effects of meso-2,3-dimercaptosuccinic acid on methylmercury-injured human fetal astrocytes in vitro. PMID- 6257540 TI - Clustering of gangliosides in phospholipid bilayers. PMID- 6257541 TI - The apparent production of superoxide and hydroxyl radicals by hematoporphyrin and light as seen by spin-trapping. PMID- 6257542 TI - Inhibition of acetylcholinesterase by 3-methoxy catecholamine derivatives. PMID- 6257544 TI - AQUI: a more easily purified isoschizomer of AVAI. PMID- 6257543 TI - Inhibition of thyrotropin-stimulated cyclic AMP accumulation by human thyroglobulin in human cultured thyroid cells. PMID- 6257545 TI - Discrimination between the N-ethylmaleimide mersalyl-sensitive protein(s) and the nucleotide translocator in pig heart mitochondria. PMID- 6257546 TI - Glucocorticoid receptor-mediated stimulation of 5'-nucleotidase in human lymphoblastoid IM-9 cells. PMID- 6257547 TI - Exploration of the role of sodium in the alpha-adrenergic regulation of hepatic glycogenolysis. PMID- 6257548 TI - An in vitro system to study the action potential sodium channel. PMID- 6257549 TI - The protection role of pyruvate against heat inactivation of N-acetylneuraminate lyase. PMID- 6257550 TI - Inhibition of Semliki Forest and herpes simplex virus production in alpha difluoromethylornithine-treated cells: reversal by polyamines. PMID- 6257551 TI - Evidence for mesangial glomerular receptors for angiotensin II linked to mesangial cell contractility. PMID- 6257552 TI - Protein kinase II has two distinct binding sites for cyclic AMP, only one of which is detectable by the conventional membrane-filtration method. PMID- 6257553 TI - Production of superoxide anion by an NADPH-oxidase from rat pulmonary macrophages. PMID- 6257554 TI - Electrical correlates of secretion in endocrine and exocrine cells. AB - Many types of secretory cells including neurons and cells of endocrine and exocrine glands show changes in electrical potential and resistance when secretion is stimulated. These electrical correlates result from the movement of ions across the cell membrane through specific ion-selective channels. In neurons and certain endocrine cells (such as pancreatic beta cells and certain cells of the anterior pituitary), these channels are voltage dependent and open transiently upon depolarization leading to action potentials. Thus some endocrine cells are electrically excitable, a property previously held to occur only in nerve and muscle. In other nonexcitable endocrine and exocrine cells (such as the pancreas and parotid), ion channels are responsive to either occupancy of specific membrane receptors or changes in intracellular metabolites and second messengers. Ion fluxes through these latter channels also lead to changes in the electrical potential and resistance, but these changes are generally more sustained and action potentials are not seen. The entry of Ca2+ through both voltage-dependent and voltage-independent ion channels plays a major role in the activation of secretion via exocytosis. PMID- 6257555 TI - Regulation of acetylcholine receptors by endogenous cotransmitters: studies of adrenal medulla. AB - The coexistence of neuropeptides and amine transmitters in the same neuron and the presence of postsynaptic receptors for these compounds invite speculation that the compounds may interact postsynaptically. To study this interaction, we selected the synapse between the splanchnic nerve and the chromaffin cells of adrenal medulla because the splanchnic nerve contains acetylcholine and neuropeptides (multiple molecular forms of enkephalin-like peptides), while the membranes of chromaffin cells contain receptors for acetylcholine and opiate peptides. When the opiate receptors are occupied by specific agonists, these agonists inhibit the expression of acetylcholine receptors. Both the acetylcholine binding and catecholamine release by acetylcholine were inhibited. It is suggested that peptides and acetylcholine coexisting in the splanchnic nerve might act as cotransmitters, there by modulating the sensitivity of acetylcholine receptors. Multiple molecular forms of enkephalin-like peptides are stored in chromaffin cells and are released by acetylcholine. A role for the opiate receptors in the modulation of the secretion of opiate peptides stored in chromaffin cells is not evident. PMID- 6257556 TI - Electrophysiologic assessment of receptor changes following chronic drug treatment. AB - Electrophysiological techniques offer a direct cellular approach to questions of neurotransmitter receptor-drug interaction. Although these methods demand considerable technical expertise and advanced instrumentation, as well as satisfaction of certain biological and pharmacological provisos, they are capable of providing detailed information on the functional status of receptors not readily attained from studies on disrupted cell systems. The development of improved methods for the quantitative comparison of changes in transmitter responsiveness after chronic experimental manipulations now makes possible the application of these electrophysiological approaches to current problems in neuropharmacology. This paper reviews the technical and biological considerations that underlie tha analysis of these problems by electrophysiology and illustrates some of the interpretative pitfalls. PMID- 6257557 TI - Superoxide dependent lipid peroxidation. AB - Rat liver microsomal NADPH-dependent lipid peroxidation and xanthine oxidase promoted lipid peroxidation were reviewed and compared to see if a unified mechanism is involved in each system. These systems were also compared to hydroxyl radical-dependent lipid peroxidation in order to determine the physiological significance of the different mechanisms of lipid peroxidation. Fenton's reagent very readily promotes lipid peroxidation, which is inhibited by catalase and hydroxyl radical traps but not by superoxide dismutase. However, the addition of ADP to Fenton's reagent results in a type of lipid peroxidation that is not inhibited by hydroxyl radical traps and the amount of hydroxyl radical spin trap adducts formed is much less. Xanthine oxidase-promoted lipid peroxidation is not inhibited by catalase and is greatly stimulated by ADP. Microsomal NADPH-dependent lipid peroxidation is also dramatically stimulated by ADP in Tris buffer but not in phosphate buffer. Hydroxyl radical traps are without effect in both microsomes and xanthine oxidase-promoted lipid peroxidation. These results suggest several in vitro mechanisms for the initiation of lipid peroxidation but do not support the hydroxyl radical for a role in physiological lipid peroxidation. PMID- 6257558 TI - Association of lipid peroxidation and polymerization of membrane proteins with erythrocyte aging. AB - The addition of malondialdehyde to erythrocytes in vitro causes a decrease in bands 1 and 2 of spectrin and an increase in high molecular weight protein polymers. Additionally, this agent causes the formation of fluorscent chromolipids characteristic of those produced during the peroxidation of endogenous membrane phospholipids. These same alterations in proteins and lipids are observed in the membranes of older cells fractionated from freshly drawn blood and in the membranes of reticulocytes induced by treatment of animals with phenylhydrazine, but not in reticulocytes induced by bleeding. The former reticulocytes have a much shorter half-life in the circulation than do either normal erythrocytes or reticulocytes produced consequent to bleeding. These experiments and the apparent paradox of "young" reticulocytes with short half lives suggest that the in vivo polymerization of membrane proteins consequent to radical-induced peroxidation of membrane lipids may contribute to the altered rheological behavior and hence to the splenic sequestration of cells. They also suggest that increases in intrinsic membrane rigidity due to lipid peroxidation, malondialdehyde, and protein polymerization may be a common feature of both aging in normal erythrocytes and in the accelerated aging that accompanies the administration of radical-generating, hemolytic agents. However, it is cautioned that other polymerization reactions involving disulfides, calcium, or direct radical attack on protein monomers may also be important determinants of the visco-elastic properties of erythrocyte membranes. PMID- 6257559 TI - Mechanisms for generating cell membrane antigens that are recognized by cytotoxic T lymphocytes. AB - Studies with many viruses have revealed that viral specific protein synthesis is an obligatory step in generating antigens on target cells for antiviral cytotoxic T lymphocytes. This has been most clearly demonstrated with DI particles, virions that are structurally complete but lack infectious RNA. Adsorption of such particles onto target cell membranes does not render these cells susceptible to lytic attack by antiviral effector cells, unless some viral protein synthesis transpires. However, some viruses, such as Sendai virus, circumvent the requirement for viral protein synthesis via fusion of the viral envelope with the target cell membrane, a process mediated by a specialized fusion protein. Once inserted into the lipid bilayer, it is likely that viral components and self H-2 noncovalently associate so that the complex can be recognized by antiviral cytotoxic T cells. This idea is supported by the demonstration that viral proteins and H-2 containing membrane proteins, incorporated into reconstituted membrane vesicles or liposomes are recognized by cytotoxic T cells. These data further show that native rather than altered viral and H-2 molecules are the moieties recognized. Associations between antigen and H-2 have been detected by a variety of techniques and in some cases are not random but selective; that is, viral antigens perferentially associate with some H-2 alleles and not others. In summary, these findings indicate that although viral antigens are present in the mature virions, these components are not recognized by antiviral killer cells until integrated into the plasma membrane. This may be achieved either through direct fusion of the viral envelope with the target cell or following viral protein synthesis and insertion of viral antigens into the plasma membrane. PMID- 6257560 TI - [Effect of thiamine, thiamine phosphates, and flavin adenine dinucleotide on neuromuscular transmission in smooth muscle]. PMID- 6257561 TI - [Effect of iodinated, hypocholesteremic preparations, and ACTH on incorporation of labeled cholesterol into the adrenal glands]. PMID- 6257562 TI - [Features of metabolism in subcellular fractions of the motor cortex during restoration of visual nerve impulses]. AB - Experimental data are obtained on cytochromoxidase (CO), acetylcholinesterase (AchE), MAO and ATPase activities in subfractions of synaptosomes and cellular mitochondria from the rabbit motor cortex following long-term visual deprivation. The first stage is characterized by elevated protein content and activation of enzymatic systems except K+; Na+--ATPase and CO. The tendency towards normalizing of protein content and activity of enzymes, particularly AchE and MAO occurred within 4 weeks. These data show that changes of enzymatic activity in subcellular components of the motor cortex following the sensory deprivation, are reversible but the process of neuronal recompensation in the integrative--starting system is complex and demands a longer time than in visual one. PMID- 6257563 TI - [Possible role of sympathetic influences and cAMP in centrifugal inhibitory control of the gustatory receptor apparatus]. AB - The electrophysiological analysis of the taste total impulse activity of the rat revealed the inhibitory influence of the gastric distention on the salt and sour taste responses to be decreased by cutting of the neck sympathetic nerve and prevented by the propranolol injection into the taste epithelium. Salt and sour taste responses were diminished by the injection of isoproterenol, cAMP, dibutyril--cAMP, and the inhibitors fo phosphodiesterase theophilline and paraverine; the activator of phosphodiesterase nicotine acid increased the taste responses. The finding suggest that the adrenergic transmitters and cAMP take part in the actualization of the inhibitory centrifugal influences. PMID- 6257564 TI - Structure of the bacteriorhodopsin proton pump of Halobacterium halobium and other membrane proteins. PMID- 6257565 TI - Surface-membrane defects in muscular dystrophy. PMID- 6257567 TI - Cell density and L-leucine transport in simian-virus-40-transformed 3T3 cells. PMID- 6257566 TI - Virally mediated changes in cellular permeability. PMID- 6257569 TI - Measurement of differential reactivities at restriction endonuclease sites. PMID- 6257568 TI - The biochemistry of human endothelial cells in culture. PMID- 6257570 TI - Detection of the src-gene product pp60src and its associated protein kinase on the surface of Rous-sarcoma-virus-transformed cells. PMID- 6257571 TI - RNA polymerase-binding sites on the bacterial plasmid pMB9. PMID- 6257572 TI - New solid-phase methods in the synthesis of natural peptides. PMID- 6257575 TI - Effects of anti-embryonal carcinoma serum on aggregation and metabolic cooperation between teratocarcinoma cells. PMID- 6257574 TI - Crystallization of cytochromes in the mitochondrial electron-transfer chain. PMID- 6257573 TI - Structure and regulation of the messenger RNA coding for the corticotropin /beta lipotropin precursor. PMID- 6257578 TI - [Human cytomegalovirus and congestive cardiomyopathy (author's transl)]. AB - Congestive cardiomyopathy in 3 cases, in which occurrence of human Cytomegalovirus (CMV) infection was demonstrated, is described. In all cases significant rise in total CMV antibodies and in early antigen-antibodies was found: CMV was also isolated from urine and saliva in one, a 13 years old boy, and only from urine in the others two patients, 20 and 26 old men. Immunoglobulin M was raised only in the first case, in which CMV infection was likely in act: instead in the others two CMV infection was late primary or recurrent. The possibility of CMV infection as etiological agent of dilatative cardiomyopathy with congestive heart failure in this 3 cases is, in our opinion, strongly suggestive. PMID- 6257577 TI - [The acromegalic heart disease (author's transl)]. AB - The clinical and pathological findings of 3 patients with acromegalic heart disease are reported. In 2 of them no other causes of the cardiopathy could be recognized but a primitive involvement of the myocardium. The GH is responsible of cardiac hypertrophy without overload, which would shift towards progressive congestive heart failure. A possible depletion of intramyocardial cathecolamines is postulated in acromegalic heart disease as much as in cardiomegalies with pressure or volume overload. PMID- 6257576 TI - Effect of bovine pituitary hormone preparations on newt lens regeneration in vitro: stimulation by thyrotropin. PMID- 6257579 TI - [The ortho-nitrophenyl-sulfenyl derivative of pentagastrin: an antagonist of gastrin receptors? A promising line of research]. PMID- 6257580 TI - [Inhibitory action of a pentagastrin analog on the rat gastric acid secretion (author's transl)]. PMID- 6257582 TI - Influence of dietary manipulations on rat kidney gluconeogenesis during acute intoxication with carbon tetrachloride. PMID- 6257581 TI - Structure-activity relationships of interactions of thyroxine analogs with intact hepatic nucleic receptors. PMID- 6257583 TI - Characterization of the atrial alpha-receptor of the rat as a subgroup of the postsynaptic alpha-adrenoceptor. PMID- 6257584 TI - Saturable 3,5,3'-triiodo-L-thyronine-binding sites in liver nuclei of rainbow trout (Salmo gairdneri Richardson). PMID- 6257585 TI - [Certain properties of transcribed fragments of the mouse genome cloned in plasmid pBR322]. AB - Clones of total mouse DNA efficiently hybridized with mRNA (or cDNA) were selected by colony hybridization technique. The majority of selected fragments demonstrate hybridization with cDNA, dsRNA-B (isolated from pre-mRNA) and oligo(dT). The data obtained indicate that the base sequences hybridizing to these test-probes are contiguous within several individual cloned restriction DNA fragments. At least in two cases sequences hybridizing with cDNA belong to repetitive fraction of the mouse genome (presumptive repetitive structural genes). They are transcribed effectively, and respective mRNAs of abundant type. Two other clones contain structural genes which are expressed into mRNAs of non abundant type. PMID- 6257586 TI - [Use of a transposon determining tetracycline resistance (Tn10) in genetic studies of cholera vibrios]. AB - Introduction of tetracycline-resistance transposon Tn10 into Rts1 (Km), a plasmid which is temperature-sensitive for DNA replication, made it possible to construct pNS10 (Km Tc) plasmid used as a vehicle for transferring Tn10 from Escherichia coli to cholera vibrio V. El Tor 218 as a result of intergeneric crosses. While being translocated from the plasmid genome to the chromosome of cholera vibrio transconjugants, Tn10 was able of insertion into structural genes thus leading to the formation of auxotrophic mutants. Ability of Tn10 to promote chromosomal rearrangements of the regions linked to Tn-element insertion site was used for identification of some structural genes in the neighbourhood of Tn-element insertion site. PMID- 6257588 TI - [Plasmid elimination from Escherichia coli K-12 cells by coumermycin]. PMID- 6257587 TI - [Genetics and phenogenetics of the hormonal characteristics of animals. VI. Functional activity of certain chemoreceptors connected with the pituitary adrenal system of silver foxes selected for their behavior]. AB - Seasonal differences in the reaction of the pituitary-adrenal system in domesticated and non-domesticated silver foxes of both sexes to substances activating alpha-, beta-adrenoreceptors, and serotonin receptors were studied. It was shown that the reactivity of the pituitary-adrenal system in silver foxes of either type of behaviour is due, at least partially, to seasonal differences in the state of adrenergic and serotoninergic mechanisms. At the same time, in silver foxes selected for behaviour to man the reaction of the pituitary-adrenal system to the injection of substances activating adrenergic and serotoninergic receptors differs, during the year, from the reaction to these compounds in non selected animals. The conclusion was made, that in the process of domestication changes take place in the state of serotonin- and noradrenaline mechanisms connected with the regulation of the hypothalamo-pituitary-adrenal complex. PMID- 6257589 TI - [Restriction and electron microscopic analyses of deletion derivatives thermosensitive with respect to maintaining plasmid pEG1]. AB - Temperature-independent deletion mutants of temperature-sensitive in self maintenance plasmid pEG-1, derived from R-factor RP4, are mapped using the restriction endonucleases PstI, SmaI, EcoRI, BamHI and the heteroduplex analysis. The pEG1 derivatives under study are found to have deletions in the area of ampicillin transposon Tn1 and nearby genes. The left and the right ends of these deletions boundaries are localized between 37.5 MD and 7.6 MD in the RP4 map. Thus far, the area of plasmid RP4 (37.5-7.6 MD) with Tn1 and, presumably, inc gene(s) in it does not have any genes needed for stable maintenance of R-factor. A conclusion is made that the gene RP4, which carries the mutation determining thermosensitive character of pEG1 maintenance and of inhibition of the cell growth, is localized between the EcoRI site and transposon Tn1 at a distance less than 1.0 MD from the latter. PMID- 6257591 TI - [Somatic hybrids of normal and tumor Djzungarian hamster cells. I. Preferential elimination of chromosomes of the normal partner]. AB - Normal Djungarian hamster lymphoid cells were fused with SV40 transformed malignant fibroblasts. The resulting 11 hybrid clones were subjected to the chromosome analysis. The karyotype of hybrids proved to be unstable. In some cases the total tetraploid number of chromosomes in hybrids drastically decreased up to the near-diploid level close to that of the malignant parent cells. The G band chromosome analysis showed that as a rule morphologically unchanged chromosomes were preferentially lost from the hybrid cells, the markers of the malignant partner being retained. On the basis of these data it is assumed than the hybrids between normal and tumour cells of Djungarian hamster preferentially lose the chromosomes of the normal parent cells during cultivation in vitro. PMID- 6257590 TI - [Transposon-induced genetic rearrangements in the chromosome of Vibrio El Tor and their application to the construction of the first genetic map of a cholera vibrio]. AB - The specificity of integration of chloramphenicol resistance transposon (Tn9) into Vibrio El Tor chromosome was studied. As shown by the isolation of auxotrophs offerring various nitritional requirements, Tn9 displayed fairly low specificity in its interaction with the chromosome. When inserted into cholera vibrio chromosome, Tn9 induced secondary rearrangements of genetic material. Nutritional requirements were identified for the polyauxotrophic clones which resulted from the mutations in chromosome region adjacent to the insertion sites of Tn9 and Tn10. Based on these observations a preliminary map was constructed for certain regions of V. eltor chromosome. PMID- 6257592 TI - [Somatic hybrids of normal and tumor Djzungarian hamster cells. II. Manifestation of malignancy and karyotype features of hybrid tumors]. AB - The hybrid clones derived from the fusion of tumour and normal cells of Djungarian hamster were tested for their ability to grow progressively in vivo and to form colonies in semisolid medium. In all cases the hybrids were able to produce tumours in animals, but tumorigenicity of different clones varied. Some clones had high take incidence of tumours comparable to that of malignant partner, others had a very low one. The hybrid clones differed in their ability to form colonies in soft agar. No correlation was found between the malignancy of the hybrid clones in vivo and their ability to grow in semisolid medium. Chromosome analysis of 23 hybrid tumours arising from the injections of the hybrid cells showed that in 18 tumours the drastic reduction of chromosomes from tetraploid to near-diploid level, comparable to that of malignant parent, took place. As a rule, morphologically unchanged chromosomes were preferentially lost from the hybrid tumour cells, the markers of the malignant partner being retained. Some hybrid tumours showed insignificant chromosome elimination of all pairs, except chromosomes of the IV and VIII pairs, their number always being reduced. PMID- 6257593 TI - Effects of vasoactive intestinal peptide and pancreatic polypeptide in rabbit intestine. AB - The effects of porcine vasoactive intestinal peptide (VIP) and bovine pancreatic polypeptide (PP) on jejunal, ileal, and colonic fluid transport were studied in the rabbit. VIP produced secretion in the small intestine (jejunum greater than ileum) but did not affect absorption in the colon. PP had no secretory effects in jejunum, ileum, or colon. The small intestinal secretion induced by VIP was not associated with raised cAMP concentrations in the mucosa; this suggests that the secretory effects of VIP in vivo are mediated by a mechanism other than stimulation of adenylate cyclase. PMID- 6257595 TI - Theca and granulosa cell tumors and endometrial adenocarcinoma. PMID- 6257594 TI - Granular cell myoblastoma of the common bile duct treated by biliary drainage and surgery. AB - A young Caucasian woman is described in whom obstructive jaundice was caused by a granular cell myoblastoma of the common bile duct. She was treated by percutaneous transhepatic biliary drainage for 10 days, before radical removal. Granular cell myoblastomas are benign lesions of disputed histogenesis, rare among biliary neoplasms, the excision of which is curative. PMID- 6257596 TI - Chemotherapy in management of mixed mesodermal tumors of the ovary. PMID- 6257597 TI - [Burkitt's tumor]. PMID- 6257598 TI - [Stationary cancer follow-up care of the Working Society for Cancer Control for Carriers of the Legal Health and Pension Insurance in the North Rhenish Westphalian Land (ARGE) using the example of the health resort Quellental]. PMID- 6257599 TI - [The phlebological consultation. Part 2: Therapy and after-care]. PMID- 6257600 TI - [Characteristics of SV 40-transformed mouse cell lines transplantable to syngeneic hosts (author's transl)]. PMID- 6257602 TI - [Scintigraphy of acute myocardial infarction with ligands of 99mTc-phosphate]. AB - Of the wide range of radiopharmaceuticals which accumulate in acutely myocardial tissue and subsequently enable its scintigraphic detection compounds of 99mtechnetium phosphate have proven clinically practicable in numerous investigations. As opposed to the similarly non-invasive method of myocardial scintigraphy with ionic tracers (201thallium scintigraphy), infarct detection through positive delineation is possible, at the earliest, six to twelve hours faster the onset of pain and meaningful for those in whom the classical ECG and enzyme changes are equivocally diagnostic and for patients with delayed hospital admissions. After approximately one week the concentration of activity in the necrotic zone and, in turn, its detectability, declines. Persistent activity is indicative of extensive infarction and poor prognosis. The sensitivity of the infarct scintigram, which is primarily carried out with 99mTc-pyrophosphate or 99mTc-methylendiphosphonate, is about 86% with small and sudbendocardial infarcts more frequently eluding detection. The method corresponds with electrocardiographic assessment of localization. The combination with 201thallium scintigraphy is useful in differentiating remote from acute infarction and in detection of right ventricular involvement associated with inferior infarction. In spite of a good correlation between the experimentally-determined infarct weight and scintigraphic findings, clinical investigations employing conventional methods of measurement (scintillation camera) have not been able to yield an early and accurate quantification of the appearance may occur, for example, in unstable angina pectoris. Thus, a negative infarct scintigram carried out at the optimal time of uptake assumes its most useful role in ruling out acute myocardial infraction in the presence of otherwise equivocal clinical findings. PMID- 6257601 TI - [The technetium-99-m-pyrophosphate scintigram in the assessment of the size of acute myocardial infarction: comparison with CK-(MB) curves mortality (author's transl)]. AB - While the technetium-99m-pyrophosphate scintigram enables diagnostic proof of acute myocardial infarction, its use in the evaluation of the extent of infarction has not been clearly established. This study, in 30 patients with acute myocardial infarction was, thus, undertaken to assess the relationship between the findings of the technetium-99m-pyrophosphate scintigram, with respect to infarct area and uptake pattern, the infarct size, as determined from the total CK an CK-MB curves, and the mortality. The scintigraphically determined infarct areas ranged between 1.7 and 29.3 cm2; the 20.2 plus or minus 6.0 cm2 average for anterior wall infarction (n=18, range 7.4 to 29.3 cm2) was significantly greater (p smaller than 0.005) than the 8.3 plus or minus 5.3 cm2 average for inferior infarction (n=12, range 1.7 to 15.8 cm2). Correlation coefficients between the scintigraphically and enzymatically determined infarct sizes for the entire patient population ranged from 0.71 to 0.80. Anterior infarctions correlated more closely (0.66 to 0.84) than inferior infarctions (0.46 to 0.66). The technetium-99m-pyrophosphate uptake pattern was focal in 20 patients and ring-shaped (doughnut) in ten. Infarcts with focal uptake patterns were significantly smaller than those displaying a doughnut pattern (12.2 plus or minus 6.4 vs. 24 plus or minus 4.0 cm2, p smaller than 0.005). The infarct weight calculated from the CK-MC curve with application of individually determined disappearance rate for those infarcts displaying a focal uptake pattern was 34 plus or minus 29 grams while that associated with a doughnut uptake pattern was significantly greater at 86 plus or minus 25 grams (p smaller than 0.005). During the 18 -month observation period there were six deaths; the average scintigraphic infarct area of 22.8 plus or minus 3.6 cm2 in those who died was significantly greater (p smaller than 0.005) than that of the 13.8 plus or minus 8.2 cm2 of the survivors. Of the non-survivors, five had a doughnut uptake pattern and one displayed focal uptake. In the 24 survivors, a focal uptake pattern was found in 19 and a doughnut pattern in five. Conversely, 19 of the 20 patients with a focal uptake pattern survived while only five of the ten patients with a doughnut pattern were alive after 18 months. Thus, comparison with the enzymatically determined infarct weight as well as the mortality indicate that the technetium 99m-pyrophosphate scintigram yields clinically relevant data with regard to infarct size. Since no patient with an infarct area of less than 17 cm2 died within the 18-month observation period, designation of scintigraphically determined infarct size as small (smaller than 17 cm2) and large (larger than 17 cm2) was enabled. The corresponding cut-off point between large and small infarctions as determined enzymatically has been designated at 65 grams. Accordingly, agreement was found in 70% (14 of 20 patients) with scintigraphically small infarcts and in 80% (8 of 10 patients) with scintigraphically large infarcts... PMID- 6257603 TI - Asialoglycoproteinemia in a case of primary hepatic cancer. AB - This article reports on a case with the most unusual finding of asialoglycoproteinemia. The patient was a man aged 40 years suffering from primary hepatic cancer. Among the various serum glycoproteins tested, the concentration of the desialylated form of alpha 2-HSglycoprotein, transferrin and alpha 2-antitrypsin was markedly elevated. The asialoprotein/sialoprotein ratio varied with each glycoprotein. In the case of transferrin, the ratio changed considerably in the course of the disease, and was found to be clearly related to the change in size of the hepatic tumor. PMID- 6257604 TI - Effect of dibutyryl cyclic AMP on gastric secretion and mucosal blood flow. AB - The effects of dibutyryl cyclic AMP (db cAMP) on gastric secretion and blood flow were determined in studies on anesthetized and conscious dogs. In 6 experiments on animals under chloralose-urethane anesthesia, gastric secretion, gastric mucosal and left gastroepiploic artery blood flows were measured. In 8 experiments on 4 conscious dogs with gastric fistulas and Heidenhain pouches, gastric secretion and gastric mucosal blood flow were measured in both the stomach and pouch. Gastric secretion was stimulated with intravenous histamine at a dose of 80 microgram/kg-hr for 3 hours, in each of the above experiments. In the second hour db cAMP was infused intravenously at a dose of 0.5 mg/kg-min. In all experiments db cAMP increased gastric mucosal blood flow, but only in the first group of dogs was there an increase in gastric acid secretion. It is concluded that db cAMP at the dose employed, had a vasodilator effect on the gastric mucosa, which does not appear to depend upon the secretory response to the drug. PMID- 6257605 TI - Effect of parathyroid hormone on jejunal electrolyte and water transport and cyclic nucleotide formation in the rat. AB - The effect of parathyroid hormone (PTH) on jejunal sodium, calcium, and water transport in situ was studied in thyroparathyroidectomized rats using the ligated loop instillation model. The acute administration of bovine PTH to the animals induced a significant increase in net sodium and water secretion when compared to animals receiving the vehicle only. This effect was due to an increase in unidirectional mucosa-to-lumen sodium flux. However, no change of calcium fluxes was observed. This acute in vivo effect on PTH could not be explained by an action via the adenyl or guanyl cyclase systems since bPTH failed to induce changes of cAMP or cGMP formation in isolated jejunal cells. Thus, other so far not elucidated mechanisms of action must be involved. PMID- 6257607 TI - Thymidine-5'-triphosphatase: a new human serum enzyme activity and its significance in malignant diseases. PMID- 6257606 TI - Glucagon secreting clones of rat islet cell tumor. PMID- 6257608 TI - Evaluating psychiatric discharge and aftercare in a VA medical center. PMID- 6257609 TI - Studies on three biochemical polymorphic systems; phosphoglucomutase (locus one) PGM1, adenylate kinase-AK & pseudocholinesterase (E2 locus)-PCE2, in human bloodstains subjected to tropical & temperate climatic conditions. PMID- 6257611 TI - Effects of short term lithium chloride administration on certain aspects of ascorbic acid metbalism in rats. PMID- 6257610 TI - The isolation, long-term cultivation and characterization of bovine peripheral blood monocytes. AB - Bovine peripheral blood monocytes were isolated from buffy coats of ACD anticoagulated whole blood. Cells cultivated on plastic surfaces for 20 h were judged to be 95% monocytes based on nonspecific esterase-1 staining, uptake of latex particles and surface receptor characteristics. Bovine monocytes were maintained up to 80 days in vitro in Dulbecco's modified Eagle medium with 15% horse serum and 15% foetal bovine serum. Several morphological and physiological features of bovine monocytes were examined during the course of culture. Cell size and cytoplasmic spreading, granulation and vacuolization increased progressively. Multinucleated giant cells predominated during the latter stages of in vitro culture. A high percentage of bovine monocytes possessed C3 and IgG Fc receptors, whereas IgM Fc and sheep erythrocyte receptors were not detected. Phagocytosis was mediated by the IgG receptor, but not by the C3 receptor. Peroxidase activity declined in a linear fashion, with cells essentially negative after 8 days of culture. Total cell protein and acid phosphatase increased during cultivation. Lysozyme activity was undetectable in both lysates and supernatants of bovine monocyte. These findings are consistent with the concept of maturation of mononuclear phagocytes. The procedures for isolation and cultivation described in this paper will provide methodology for detailed study of bovine mononuclear phagocytes. PMID- 6257612 TI - Clostridium perfringens type A enteropathy: studies with a nonenterotoxigenic strain. PMID- 6257613 TI - Carcinoma of the male breast. (A clinicopathological study of 30 cases). PMID- 6257614 TI - Fractionation and characterization of allergens extracted from eggs of Schistosoma japonicum. AB - Allergenic components were partially purified from the crude extract of eggs of Schistosoma japonicum by gel filtration on Sephadex G-200 and ion-exchange chromatography on DEAE-Sephadex A-50. Allergenic activity was assayed by the Prausnitz-Kustner type skin test with infected mouse sera and radioallergosorbent test with human ser. S. japonicum egg allergens (JEAL) showed single and three allergenic peaks, by isoelectrofocusing (PI = 4.8) and polyacrylamide gel electrophoresis, respectively. The molecular weights of JEAL were calibrated 30,000-200,000 by gel filtration. JEAL were adsorbed on the affinity columns of concanavalin A, Lentil lectin and partially wheat germ lectin. JEAL lost their allergenic activity by 0.1M periodate oxidation; however, they were resistant to heating (100 degrees C, 60 min), urea and guanidine. We suppose that the carbohydrate of JEAL is important to the allergenic determinant. PMID- 6257615 TI - Pandora's box revisited: a second look at the acetate story. PMID- 6257617 TI - The fine page. Serum angiotensin-converting enzyme activity in sarcoidosis. PMID- 6257616 TI - Experimental myringoplasty. AB - Artificial eardrums made from biodegradable poly(D,L-lactic acid), poly(glycolic acid) and poly(beta-benzyl-L-aspartate-co-L-leucine) 50/50, and made from the microporous poly(tetrafluoroethylene) and bisphenol-A poly(carbonate) membranes were implanted into the ear and as a reference subcutaneously in rats. The implants were histologically examined for periods up to one year. From the biodegradable polymers studied the poly(beta-benzyl-L-aspartate-co-L-leucine) 50/50 evoked the least tissue reaction and the newly formed tympanic membranes are the best in terms of thickness and overall integrity. The microporous poly(tetrafluoroethylene) membrane can be considered as a valuable support for the formation of a reinforced tympanic membrane. PMID- 6257618 TI - I-Naphthyl acetate esterase isoenzymes in synovial fluids and radiography of temporomandibular and knee joints. AB - Esterase isoenzymes of synovial fluids were presented in cases of pain dysfunction syndrome, osteoarthrosis, osteochondroma, malignant fibrous histiocytoma of temporomandibular joint, and hemarthrosis, rheumatoid arthritis of the knee joint. Radiographic features of them were also comparatively presented in several cases. The electrophoretogram of I-Naphthyl acetate esterase of pain-dysfunction syndrome showed the esterase-I, while when inflammatory process developed at joints, electrophoretic pattern of synovial fluids revealed a rather similar feature of sera with variable stainabilities of esterase-I, and III, irrespective of any inflammation. Osteochondroma showed two components of esterase-I and -III, on the other hand malignant fibrous histiocytoma presented esterase-I and -III in the early stage but a more complicated pattern in recurrence. Among these conditions, the most similarity between synovial fluid and serum was demonstrated in the case of hemarthrosis on the electrophoretogram of I-Naphthyl acetate esterases. PMID- 6257619 TI - Protein conformation wheels: cytochromes and lysozymes. AB - Conformation wheels, directly relating to amino acid sequence to the local torsion angles in a protein molecule, are presented for cytochromes c, c2, c550, and c551 and for lysozymes from hen egg-white and T4 bacteriophage. The circular plots for the cytochrome molecules aid in visualizing the common three dimensional folding ("cytochrome fold") observed in this family of proteins. Conformation wheels for lysozymes from two different species reveal the characteristic differences in their folding patterns. These novel plots are also useful in storing and comparing the several sets of crystallographic data reported for lysozyme. PMID- 6257620 TI - Reaction of bovine pancreatic ribonuclease A with 6-chloropurine riboside 5' monophosphate. Nuclear magnetic resonance studies of the corresponding S-peptide. AB - The n.m.r. spectra of native S-peptide and of S-peptide II, a derivative obtained after reaction of bovine pancreatic ribonuclease A with 6-chloropurine riboside 5'-monophosphate, both in D2O and in urea-d4, were obtained with a 270 MHz Fourier transform spectrometer. From these spectra it was possible to assign most of the proton resonances of the peptide and the position of the labelling group, the alpha-NH2 of Lys-1, was also deduced. PMID- 6257621 TI - Studies on the examination of imported laboratory monkey, Macaca fascicularis for E. histolytica and other intestinal parasites. AB - Infection rate of imported monkeys, under this study, with intestinal protozoa is higher than the infection rate with intestinal nematodes. Mostly encountered protozoa were E. coli, E. nana, E. histolytica and I. butschlii. Formalin-Ether concentration method yielded higher % positive for E. histolytica than the culture method using Tanabe-Chiba medium, but the results obtained from these 2 methods correlate perfectly well with each other. Efficacy of thiabendazole against intestinal nematodes such as Strongyloides, Trichuris, Physaloptera, Oesophagostomum and Capillaria was very satisfactory. PMID- 6257622 TI - Assessment of acyclovir on acute ocular infection induced by drug-resistant strains of HSV-1. AB - Effects of topical acyclovir treatment on rabbit eyes infected with parent McKrae, idoxuridine-resistant, and vidarabine-resistant strains of HSV-1 were studied. Topical acyclovir therapy given four times a day was significantly more effective than idoxuridine and vidarabine at suppressing acute herpetic ocular disease induced by either sensitive or drug-resistant strains of HSV-1. Virus isolation from neural tissues indicated that none of the therapy prevented viral infection of the nervous system. PMID- 6257623 TI - Angiotensin-converting enzyme activity in ocular fluids. AB - Angiotensin II is a biological active octapeptide that is formed by the action of angiotensin-converting enzyme (ACE) on the inactive precursor, angiotensin I. ACE activity was found in tears and aqueous humor from both rabbit and human eyes. The activity was higher in tears than aqueous humor. Enzyme activity was determined fluorimetrically from the rate of breakdown of the substrate, hippuryl L-histidyl-L-leucine. The enzyme activity was further characterized by determining the effects of inhibitors. There was a significant difference in ACE levels in human tears when eye color was considered. People with either green or brown eyes had a higher ACE level than did blue-eyed individuals. The presence of this enzyme activity in ocular fluids suggests that angiotensin II may play a role in normal ocular physiology. PMID- 6257624 TI - Inadequate status and impaired metabolism of vitamin D in the elderly. AB - The mean serum concentrations of 25-hydroxyvitamin D and of 24,25 dihydroxyvitamin D were significantly lower (P less than 0.01) in 82 elderly people than in 30 young control subjects. The levels in 30 elderly people confined to their rooms were 8.0 +/- 0.7 (SE) and 0.54 +/- 0.04 ng/ml, respectively; in 31 active old-age-home residents who spent part of their time outdoors, they were 11.4 +/- 0.8 and 0.82 +/- 0.08 ng/ml, respectively; and in 21 elderly farm workers, 14.6 +/- 1.4 and 0.98 +/- 0.10 ng/ml, respectively. In the young control subjects, the levels were 21.5 +/- 1.4 and 1.91 +/- 0.12 ng/ml, respectively. In addition, an intestinal absorption test with a standard oral dose of 25-hydroxyvitamin D3 showed that the serum 25-hydroxyvitamin D3 responses at 4 and 6 h were considerably depressed in 10 of the 20 elderly subjects in whom the test was performed. PMID- 6257625 TI - Lymphokine-induced Macrophage aggregation: the possible role of cyclic nucleotides. AB - The possible role of cyclic nucleotides in guinea pig macrophage aggregation, induced by human lymphokine (LK) has been investigated. Small increases were found in guanosine 3'5'-cyclic monophosphate (cGMP), but not adenosine 3'5' cyclic monophosphate (cAMP), levels of lymphokine aggregated macrophages. Addition of exogenous dibutyryl (DB) cAMP, L-isoproterenol, or theophylline did not induce macrophage aggregation. By contrast, both exogenous DBcGMP and carbamyl-choline induced a macrophage aggregation; although DBcGMP was more effective. In addition, both L-isoproterenol and DBcAMP in the presence of theophylline decreased LK-induced macrophage aggregation, whereas D-isoproterenol and DBcGMP had no effect. The results obtained here are discussed in the context of the previously reported effects of cyclic nucleotides on migration inhibitory factor (MIF) activity and the possible role of these agents in the mechanism of action of MIF. PMID- 6257626 TI - [Rotavirus enteritis in children]. AB - Recent clinical experience with twelve cases of rotavirus gastroenteritis has enabled us to review this subject. After a historical introduction and a review of the literature, two patients are described in detail. The clinical and laboratory data of all the twelve children are reviewed and compared with cases reported in the literature. These observations suggest several conclusions: The disease is very contagious. The patients present with diarrhoea lasting a few days, vomiting and fever. They recover without complications usually within 6 days. All our cases occurred in winter. The blood count revealed a neutrophilia at the onset of the illness followed after 4-5 days by a lymphocytosis with 1-3% plasmocytes. The finding of increased serum transaminase levels indicates a hepatic involvement. These levels returned to normal values only several weeks after the clinical improvement. Treatment consisting only of rehydration and a usual diet for acute gastroenteritis was successful in all the patients. PMID- 6257627 TI - Scirrhous carcinoma of the female breast. AB - A series of 200 consecutive breast cancers as studied retrospectively. All of the diagnoses were reviewed without knowledge of the initial response; special attention was given to the true scirrhous carcinoma of the female breast, a special form of infiltrating duct carcinoma. Seven cases, an incidence of 3.5 per cent, fulfilled the diagnostic criteria: dense and hyaline connective tissue stroma, evenly distributed throughout the tumour and at its borders and which compressed pleomorphic and scanty carcinoma cells, almost without duct formation. Ten cases, an incidence of 5.0 per cent, were initially diagnosed as scirrhous tumours but have been reclassified as pseudo-scirrhous cancers. The commonest error seems to be the confusion between true scirrhous mammary cancer and infiltrating lobular carcinoma. PMID- 6257628 TI - Radiation therapy for postoperative local-regionally recurrent lung cancer. PMID- 6257629 TI - Abdominal lymph node scanning. PMID- 6257631 TI - Water relations of glucose-catabolizing enzymes in Pseudomonas fluorescens. PMID- 6257630 TI - Relative biological effectiveness of a high energy modulated proton beam using a spontaneous murine tumor in vivo. PMID- 6257632 TI - Radioiodination of enterotoxin from Clostridium perfringens type A using chloramine T. PMID- 6257633 TI - Japanese encephalitis in Assam (report of the clinical profile of nine cases). PMID- 6257634 TI - Determination of the functions of hemolytic plasmid pHly152 of Escherichia coli. AB - The alpha-hemolytic Escherichia coli strain PM152 harbors three transmissible plasmids, which have molecular weights of 65 X 10(6) (pA152), 41 X 10(6) pHly152), and 32 X 10(6) (pC152). Plasmids pHly152 and pC152 belong to incompatibility groups J2 and N, respectively. By transforming E. coli K-12 with isolated plasmids, we showed that the genetic determinant required for hemolysis was located entirely on plasmid pHly152, and a physical map of this plasmid was constructed. By transposon mutagenesis, a deoxyribonucleic acid segment of about 3.5 X 10(6) daltons was identified as being essential for hemolysis. Most of the EcoRI and HindIII fragments of the hemolytic plasmid pHly152 were cloned by using pACYC184 and RSF2124 as vectors. Two classes of Tn3-induced hemolysis-negative mutants could be complemented by recombinant plasmids carrying fragments from the hemolysis region of pHly152, whereas a third class could be restored to hemolytic activity only by recombination between the mutant plasmids and a suitable recombinant deoxyribonucleic acid. These data suggest that there are at least three clustered cistrons which are required for hemolysis. Other EcoRI and HindIII fragments of pHly152 were identified as being essential for replication, incompatibility, transfer, and restriction. PMID- 6257635 TI - Genetic variability in Halobacterium halobium. AB - Halobacterium halobium exhibits an extraordinary degree of spontaneous variability. Mutants which are defective in the formation of gas vacuoles (vac) arise at a frequency of 10(-2). Other easily detectable phenotypes, like the synthesis of bacterioruberin (Rub) or the synthesis of retinal (Ret) and bacterio opsin (Ops), the two components which form the purple membrane (Pum) of H. halobium, are lost at a frequency of about 10(-4). With the same frequency a mutant type appears which exhibits an extremely high variability in these phenotypes. With the exception of the ret mutants, all spontaneously arising mutants show alterations, i.e., insertions, rearrangements, or deletions, in the plasmid pHH1. It appears that the introduction of one insertion into pHH1 triggers further insertions, which makes the identification of relationships between phenotypic and genotypic alterations rather difficult. From the analysis of a large number of spontaneous vac mutants and their vac+ revertants it can be concluded that the formation of the gas vacuoles is determined or controlled by plasmid genes. No such conclusion is yet possible for the rub mutants, although all mutants of this type so far analyzed exhibit a defined insertion. pum mutants which have lost the capability of forming bacterio-opsin carry insertions in the plasmid which are distributed over a rather large region of the plasmid. No strains of H. halobium could be obtained which had lost plasmid pHH1 completely. PMID- 6257636 TI - Isolation and characterization of linear deoxyribonucleic acid plasmids from Kluyveromyces lactis and the plasmid-associated killer character. AB - Two linear deoxyribonucleic acid plasmids, designated pGK11 and pGK12, were isolated from the yeast Kluyveromyces lactis IFO 1267. pGK11 and pGK12 had molecular weights of 5.4 X 10(6) and 8.4 X 10(6), respectively. Both plasmids possessed the same density of 1.687 g/cm3, lighter than the densities of mitochondrial (1.692 g/cm3) and nuclear (1.699 g/cm3) deoxyribonucleic acids. A restriction map of pGK11 was constructed from digestions by EcoRI, HindIII, PstI, and BamHI. pGK12 was cleaved by EcoRI into seven fragments and by BamHI into two fragments K. lactis IFO 1267 killed Saccharomyces cerevisiae sensitive and killer strains and certain strains of Saccharomyces italicus, K. lactis, Kluyveromyces thermotolerans, and K. vanudenii. All K. lactis strains lacking the pGK1 plasmids were nonkillers. A hybrid was constructed between K. lactis IFO 1267 and a nonkiller K. lactis strain lacking the plasmids and subjected to tetrad analysis after sporulation. The killer character was extrachromosomally transmitted in all tetrads in association with the pGK1 plasmids. The double-stranded ribonucleic acid killer plasmid could not be detected in any K. lactis killer strains. It is thus highly probable that the killer character is mediated by the linear deoxyribonucleic acid plasmids. A single chromosomal gene was found which was responsible for the resistance to the K. lactis killer. PMID- 6257637 TI - In vivo role of the relA+ gene in regulation of the lac operon. AB - Under conditions of amino acid limitation, beta-galactosidase was produced at a 70-fold higher rate in a relA+ strain than in an isogenic relA strain of Escherichia coli K-12. Under identical conditions with the relA+ and relA strains carrying various lac promoter mutations, rates of beta-galactosidase synthesis in relA+ (relative to relA) ranged from 26-fold higher (promoter mutant Pr 13) to only 5-fold higher (promoter mutant PrL8uv5). This promoter specificity was independent of strain background and the means of eliciting amino acid limitation. Addition of cyclic AMP to the growth medium altered the relA+/relA difference for beta-galactosidase synthesis from the wild-type lac promoter. The experiments suggest that the relA+/relA difference in lac expression arises primarily at the point of transcription initiation. The results are discussed in relation to recent in vitro data showing a promoter-specific guanosine 5' diphosphate 3'-diphosphate stimulation of lac transcription (P. Primakoff and S. W. Artz, Proc. Natl. Acad. Sci. U.S.A. 76:1726-1730). PMID- 6257638 TI - Molecular cloning and expression of Bacillus licheniformis beta-lactamase gene in Escherichia coli and Bacillus subtilis. AB - The chromosomal beta-lactamase (penicillinase, penP) gene from Bacillus licheniformis 749/C has been cloned in Escherichia coli. The locations of the target sites for various restriction enzymes on the 4.2-kilobase EcoRI fragment were determined. By matching the restriction mapping data with the potential nucleotide sequences of the penP gene deduced from known protein sequence, we established the exact position of the penP gene on the fragment. A bifunctional plasmid vector carrying the penP gene, plasmid pOG2165, was constructed which directs the synthesis of the heterologous beta-lactamase in both E. coli and Bacillus subtilis hosts. The protein synthesized in E. coli and B. subtilis is similar in size to the processed beta-lactamase made in B. licheniformis. Furthermore, the beta-lactamase made in B. subtilis is efficiently secreted by the host into the culture medium, indicating that B. subtilis is capable of carrying out the post-translational proteolytic cleavage(s) to convert the membrane-bound precursor enzyme into the soluble extracellular form. PMID- 6257639 TI - Manganese and defenses against oxygen toxicity in Lactobacillus plantarum. AB - Lactobacillus plantarum is aerotolerant during log-phase growth on glucose, but is an obligate aerobe on polyols. Respiration was cyanide resistant and under certain conditions was associated with the accumulation of millimolar concentrations of H(2)O(2). On glucose, optimal growth was observed in the absence of O(2). Extracts of L. plantarum did not catalyze the reduction of paraquat by reduced nicotinamide adenine dinucleotide, but plumbagin (5-hydroxy-2 methyl-1,4-naphthoquinone) was readily reduced. Such extracts produced O(2) (-) in the presence of NADH plus plumbagin. Plumbagin caused a 10-fold increase in the rate of respiration of intact cells in the presence of glucose and also imposed a loss of viability which was dependent upon both glucose and O(2). Although extracts of L. plantarum were devoid of true superoxide dismutase activity, this organism was comparable to superoxide dismutase-containing species in its resistance toward hyperbaric O(2) and toward the oxygen-dependent lethality of plumbagin. L. plantarum required Mn-rich media and actively accumulated Mn(II). Soluble extracts were found to contain approximately 9 mug of Mn per mg of protein and 75 to 90% of this Mn was dialyzable. Such extracts exhibited a dialyzable and ethylenediaminetetraacetic acid-inhibitable ability to scavenge O(2) (-). This O(2) (-)-scavenging activity was due to the dialyzable Mn(II) present in these extracts and could be mimicked by MnCl(2). Cells grown in Mn-rich media were enriched in dialyzable Mn and were more resistant toward oxygen toxicity and toward the oxygen-dependent plumbagin toxicity than were cells grown in Mn-deficient media. L. plantarum exhibited no nutritional requirement for iron and little or no iron was present in these cells, even when they were grown in iron-rich media. L. plantarum thus appears to use millimolar levels of Mn(II) to scavenge O(2) (-), much as most other organisms use micromolar levels of superoxide dismutases. PMID- 6257640 TI - Distribution of Tn551 insertion sites responsible for auxotrophy on the Staphylococcus aureus chromosome. AB - A method was devised to efficiently select isolates of Staphylococcus aureus 8325 in which Tn551, a transposon originating on the pI258 plasmid responsible for erythromycin resistance (Emr), had translocated to the host chromosome. This method consisted of selecting for Emr at 43 degrees C with a strain in which the pI258 plasmid was unable to replicate at 43 degrees C because of a temperature sensitive plasmid mutation. By selecting isolates that were Emr at 43 degrees C and auxotrophic for nutrients not required by the parent strain. Tn551-induced auxotrophic mutants were readily isolated. The incidence of auxotrophic classes was not random; 80% of the isolates in one experiment were Trp-, whereas only a single example of each of some of the other classes was isolated. Among the Trp- mutants, the distribution of trp genes affected and the frequency of precise excision of Tn551 from individual sites varied. When analyzed by transformation, the Tn551-induced ala, his, ilv, lys, rib, thrA, thrB, and trp mutations were shown to occupy sites previously defined by nitrosoguanidine-induced mutations. Tn551-induced mutagenesis provided three previously unrecognized classes of auxotrophs (tyr, met, and thrC), and the Tn551 integration sites resulting in these mutations have been identified. In addition, a chromosomal region (uraB) was identified by Tn551 mutagenesis that is distinct from uraA (previously defined by chemical mutagenesis). Some Tn551-induced mutations (most notably pur) could not be linked to the known linkage groups of the chromosome by transformation. With the exception of two pur mutations, all of the Tn551-induced auxotrophic mutational sites cotransformed at unity with Tn551 and, in cases in which they were selected, prototrophic transformants were always Ems. Thus, the Tn551 and auxotrophic sites are identical. PMID- 6257642 TI - Genetic analysis of the RecE pathway of genetic recombination in Escherichia coli K-12. AB - The RecE pathway of genetic recombination in Escherichia coli K-12 was defined to be the pathway that is utilized in deoxyribonucleic acid exonuclease V (ExoV) defective cells which express constitutively recE+, the structural gene for deoxyribonucleic acid exonuclease VIII. Dependence on ExoVIII was shown by the occurrence in a recB21 sbcA23 strain of recombination deficiency mutations in recE, the structural gene for ExoVIII. Point mutations in recE were found as well as deletion mutations in which the entire Rac prophage, carrying recE, was lost. In addition, strain construction and mutagenesis revealed the dependence of the RecE pathway on recA+ and on recF+. Dependence on a fourth gene was shown by a mutation (rec-77) which does not map near the other genes. The problem of distinguishing the RecE pathway from that previously called RecF is discussed. PMID- 6257641 TI - Evidence for a chromosome-borne resistance transposon (Tn916) in Streptococcus faecalis that is capable of "conjugal" transfer in the absence of a conjugative plasmid. AB - Streptococcus faecalis strain DS16 harbors the conjugative hemolysin-bacteriocin plasmid pAD1 (35 megadaltons) and the nonconjugative R-plasmid pAD2 determining resistance to streptomycin, kanamycin, and erythromycin; a tetracycline resistance (Tetr) determinant is located on the chromosome. When strain DS16 was mated (on membrane filters) with the plasmid-free strain JH2-2, Tetr transconjugants could be obtained at a frequency of about 10(-6) per recipient. Analyses of transconjugants showed that some contained the Tetr determinant linked to pAD1. Subsequent studies showed that the Tetr determinant was located on a 10-megaldalton transposon, designated Tn916, which could insert into two hemolysin plasmids: pAM gamma 1 and pOB1. In addition, derivatives of DS16 devoid of pAD1 were capable of transferring Tetr to recipient strains. Transconjugants (plasmid-free) from such matings could subsequently act as donors in the transfer of Tetr. Both transposition and transfer were found to be rec independent. PMID- 6257643 TI - Isolation and electron microscopic observations of intracytoplasmic inclusions containing Chlamydia psittaci. AB - Intracytoplasmic inclusions containing Chlamydia psittaci were isolated by a newly established method. Infected L-cells at 20 h after infection were suspended in 0.25 M sucrose-tris(hydroxymethyl)aminomethane buffer containing ethylene diaminetetraacetic acid, homogenized in a Dounce tissue grinder, and filtered through a 2,000-mesh screen. Isolated inclusions were stabilized in 5% bovine serum albumin in 10 mM tris(hydroxymethyl)aminomethane buffer. Electron microscopic observations revealed the presence of surface projections on the vegetative, reticulate bodies and a direct connection between the reticulate bodies and the inclusion membrane by means of projections. PMID- 6257644 TI - Physical maps of Klebsiella aerogenes and Salmonella typhimurium hut genes. AB - The recognition sites for several restriction endonucleases were mapped within deoxyribonucleic acid coding for histidine utilization (hut) genes of Salmonella typhimurium and Klebsiella aerogenes. Deoxyribonucleic acid fragments containing the two hut promoters were identified by ribonucleic acid polymerase binding. PMID- 6257645 TI - Structure of a naturally occurring plasmid with genes for enterotoxin production and drug resistance. AB - A physical map of the 117-kilobase conjugative plasmid pCG86 was constructed using electron microscope heteroduplex analysis. This plasmid carries the genes elt, for heat-labile enterotoxin, and estA, for heat-stable enterotoxin, as well as the genes for resistance to tetracycline, streptomycin, sulfonamides, and mercury. These genes were mapped using deletions and Tn5 insertions as physical markers. Analysis of a heteroduplex between pCG86 and a previously described enterotoxin plasmid (EntP307) showed a 48-kilobase region of complete homology which included the genes elt and estA. An 8.8-kilobase BamHI fragment of EntP307 carrying elt, cloned by others, was also shown to be completely homologous with pCG86. The position of elt on the fragment was verified, and it was shown to carry estA as well. A 44-kilobase region of pCG86 showed partial homology with the region of EntP307 previously shown to contain conjugal transfer genes. The gene for tetracycline resistance is carried on a stem-loop structure with the dimensions of Tn10, and the genes for the other drug resistance markers are carried on a 14.6-kilobase segment that forms an insertion loop in heteroduplexes with EntP307. These studies suggest that pCG86 arose either by recombination between an enterotoxin plasmid of incompatibility group FI, like EntP307, and a multiple resistance factor of incompatibility group FII, or by transposition into EntP307 of two transposons. PMID- 6257646 TI - Conjugative R plasmids in group C and G streptococci. AB - Two streptococcal isolates of groups C and G harbored conjugative R plasmids with molecular weights of 17 X 10(6) (pIP646) and 20 X 10(6) (pIP920). These plasmids carried genetic markers for resistance to macrolides and related drugs, as well as to chloramphenicol (pIP920), and have very similar HindIII restriction enzyme patterns. PMID- 6257647 TI - Genetic dissection of catalytic activities of the Salmonella typhimurium mannitol enzyme II. AB - Approximately 60 mutants of Salmonella typhimurium were isolated which exhibited altered levels of the activities of the mannitol enzyme II. The mutants were grouped into six distinct categories based on their mannitol fermentation, transport, chemotaxis, and phosphorylation activities. PMID- 6257648 TI - Properties of six pesticide degradation plasmids isolated from Alcaligenes paradoxus and Alcaligenes eutrophus. AB - Biophysical and genetic properties of six independently isolated plasmids encoding the degradation of the herbicides 2,4-dichlorophenoxyacetic acid and 4 chloro-2-methylphenoxyacetic acid are described. Four of the plasmids, pJP3, pJP4, pJP5, and pJP7, had molecular masses of 51 megadaltons, belonged to the IncP1 incompatibility group, and transferred freely to strains of Escherichia coli, Rhodopseudomonas sphaeroides, Rhizobium sp., Agrobacterium tumefaciens, Pseudomonas putida, Pseudomonas fluorescens, and Acinetobacter calcoaceticus. In addition, these four plasmids conferred resistance to merbromin, phenylmercury acetate, and mercuric ions, had almost identical restriction endonuclease cleavage patterns, and encoded degradation of m-chlorobenzoate. The two other plasmids, pJP2 and pJP9, did not belong to the IncP1 incompatibility group, had molecular masses of 37 megadaltons, encoded the degradation of phenoxyacetic acid, and possessed identical restriction endonuclease cleavage patterns. PMID- 6257649 TI - Isolation and properties of a Bacillus subtilis mutant unable to produce fructose bisphosphatase. AB - A Bacillus subtilis mutation (gene symbol fdpA1), producing a deficiency of D fructose-1,6-bisphosphate 1-phosphohydrolase (EC 3.1.3.11, fructose bisphosphatase), was isolated and genetically purified. An fdpA1-containing mutant did not produce cross-reacting material. It grew on any carbon source that allowed growth of the standard strain except myo-inositol and D-gluconate. Because the mutant could grow on D-fructose, glycerol, or L-malate as the sole carbon source, B. subtilis can produce fructose-6-phosphate and the derived cell wall precursors from these carbon sources in the absence of fructose bisphosphatase. In other words, during gluconeogenesis B. subtilis must be able to bypass this reaction. Fructose-bisphosphatase is also not needed for the sporulation of B., subtilis. The fdpA1 mutation has the pleiotropic consequence that mutants carrying it cannot produce inositol dehydrogenase (EC 1.1.1.18) and gluconate kinase (EC 2.7.1.12) under conditions that normally induce these enzymes. PMID- 6257650 TI - Deoxyribonucleic acid modifications and restriction endonuclease production in Neisseria gonorrhoeae. AB - Modification of gonococcal deoxyribonucleic acid (DNA) was investigated, and the relationship with endonuclease production was explored. Both chromosomal and plasmid DNA from different gonococcal strains, irrespective of their plasmid content, was poorly cleaved by the restriction endonucleases HaeII, HaeIII, SacII, and BamHI. The fragment pattern of the Tn3 segment present on the 7.2 kilobase gonococcal resistance plasmid, when compared to its known DNA sequence, allowed us to conclude that the HaeIII and BamHI resistance was due to modification of these sites. A comparison of the fragment pattern of the resistance plasmid, when isolated from Escherichia coli or Neisseria gonorrhoeae, revealed that the resistance of HaeII must also be due to modification of its recognition sequence. Isoschizomers of HaeII and HaeIII can be found in isolates of N. gonorrhoeae (NgoI and NgoII, respectively). A new restriction endonuclease in gonococci, NgoIII, with a specificity similar to SacII, is reported here. High pressure liquid chromatography of gonococcal DNA showed the presence of 5 methylcytosine. It is suggested that the methylation of cytosine residues in the HaeII (NgoI), HaeIII (NgoII), and SacII (NgoIII) recognition sites is the basis for the resistance of gonococcal DNA to cleavage by these enzymes. This methylation may be part of a host restriction modification system. In two out of five gonococcal strains the sequence -GATC- was modified. One strain unable to modify this sequence was a spontaneous mutant of a strain carrying such a modifying function. PMID- 6257651 TI - Transposition of the oxacillin-hydrolyzing penicillinase gene. AB - We have found that the oxacillin-hydrolyzing penicillinase gene (oxa) encoded by plasmid RGN238 transposes to various plasmids in a recA background. We call this transposable element Tn2603. Tn2603 encodes the genes for streptomycin, sulfonamide, and mercury resistance in addition to the oxa gene. Tn2603 has a molecular size of 19.6 kilobase pairs and appears to be flanked by small inverted repeat sequences of about 200 base pairs long. PMID- 6257652 TI - Escherichia coli heat-labile enterotoxin genes are flanked by repeated deoxyribonucleic acid sequences. AB - The enterotoxin regions of the heat-labile and heat-stable enterotoxin (LT+ ST+) plasmid, pJY11, originating in a clinically isolated Escherichia coli strain, have been isolated as various-sized deoxyribonucleic acid (DNA) fragments by using cloning vehicles. The structure of the LT+ region and its neighboring DNA regions was studied by utilizing these recombinant plasmids. The LT+ region consisted of at least two genes, toxA and toxB, which could complement each other in trans. The toxA- and toxB-encoded polypeptides (LT subunits A and B, respectively) were identified by their immunological cross-reactivity with Vibrio cholerae enterotoxin subunit A or B. These tox genes and the promoter(s) were localized with respect to the restriction endonuclease cleavage map. The LT+ region was flanked by repeated DNA sequences (designated as beta). Another tox gen(s), encoding ST (designated as toxS), which was also flanked by inverted, repeated DNA sequences (designated as alpha), was located between one of the beta sequences and the LT+ region. These novel DNA structures (beta-alpha-toxS-alpha toxA-toxB-beta) suggest the possibility that the LT+ region is on a transposon containing an ST transposon within the structure. PMID- 6257653 TI - Isolation and analysis of multicopy extragenic suppressors of dnaA mutations. AB - Recombinant plasmids were constructed from restriction enzyme digests of Escherichia coli chromosomal deoxyribonucleic acid and pMB9 plasmid deoxyribonucleic acid and selected for correction of the dnaA phenotype. The three plasmids isolated, all retransformed dnaA cells, both recA+ and recA, such that all tetracycline-resistant transformants selected at permissive temperature simultaneously became temperature resistant. Restriction enzyme mapping of the plasmids showed all three to be different, and it was subsequently shown that none contained the dnaA+ gene. Though each of the three plasmids suppressed three different temperature-sensitive dnaA alleles, none corrected the phenotype of an unsuppressed dnaA amber allele. It was concluded, therefore, that each plasmid contained a unique extragenic suppressor of dnaA and that the suppression was observed because of the elevated gene dosage of the cloned material. The plasmids were unstable in the absence of selection. PMID- 6257654 TI - Physical characterization of Bacteroides fragilis R plasmid pBF4. AB - Bacteroides fragilis V479-1 has previously been shown to harbor a self transmissible 27 X 10(6)-dalton plasmid (pBF4) which confers lincosamide macrolide resistance. The present study has focused on the physical properties of pBF4. The plasmid was found to be present in 1 to 2 copies per chromosomal equivalent. pBF4 was genetically stable, although spontaneously occurring plasmidless segregants could be detected at low frequency (approximately 1%). This frequency was unaffected by growth of cells in ethidium bromide. About one third of all spontaneously occurring macrolide-lincosamide-sensitive clones of strain V479-1 were found to contain pBF4 molecules that carried deletions. Ten independently obtained deletion derivatives of pBF4 from lincosamide-macrolide sensitive strains were compared with the parental pBF4 by restriction endonuclease cleavage analysis. A restriction site map of pBF4 was constructed, and the location of the deletions was approximated. Self-annealed pBF4 molecules, examined by electron microscopy, revealed the presence of two pairs of inverted repeat (IR) sequences on the plasmid. IR-1 was about 400 base pairs in length, and its two component members were separated by an intervening sequence of about 15 kilobases. IR-2 was about 75 base pairs in length, and its component members were separated by 4.2 kilobases. Each of the deletions of pBF4 studied had a terminus at or near the same IR-2 sequence. PMID- 6257655 TI - Characterization of a site-specific restriction endonuclease from Streptomyces aureofaciens. AB - A new type II sequence-specific restriction endonuclease, SauI, was isolated from Streptomyces aureofaciens IKA18/4. The purified enzyme was free of contaminating exonuclease and phosphatase activities. SauI cleaved lambda DNA at two sites, but did not cleave pBR322, simian virus 40, or phi X174 DNA. SauI recognized the septanucleotide sequence 5'-CCTNAGG-3' and cleaved at the position indicated by the arrow, producing a trinucleotide 5'-terminal extension. PMID- 6257656 TI - Transductional mapping of ksgB and a new Tn5-induced kasugamycin resistance gene, ksgD, in Escherichia coli K-12. AB - We have mapped the Escherichia coli ksgB gene to min 36.5, 0.8 min from man and 0.7 min from aroD. A new kasugamycin resistance (Ksgr) gene, ksgD, has been isolated, using a transposon, Tn5. ksgD::TN5 is 44% cotransducible with sbcA, unlinked to trp, and unlinked to man (by P1 transduction). The ksgD::Tn5 has a late time of entry from HfrB7 (PO43). These data place ksgD clockwise from sbcA (which enters early from HfrB7) at min 30.4. The reistance of ksgB ksgD single and double mutant strains has been quantitated. Single mutations, ksgB or ksgD, gave resistance to 600 micrograms of kasugamycin per ml, whereas a ksgB ksgD strain was able to grow in the presence of kasugamycin levels in excess of 3,000 micrograms/ml. This indicates that the mechanisms of resistance coded for by the two genes are independent and synergistic. PMID- 6257657 TI - Replication of M13 oriC bacteriophages in Escherichia coli rep mutant is dependent on the cloned Escherichia coli replication origin. AB - The involvement of the Escherichia coli rep protein in the replication of M13 chimeric deoxyribonucleic acids (DNAs) carrying the E. coli chromosomal DNA replication origin (oriC) has been examined. Previous studies indicate that the cloning of a 3,550-base-pair sequence of chromosomal DNA containing oriC into an M13 vector allows extensive replication of the M13 oriC chimeric DNA in an E. coli rep-3 mutant. We have extended these studies by preparing a 330-base-pair deletion that specifically deletes the oriC sequence in the M13 oriC DNAs, to demonstrate that the replication observed in the rep-3 host is dependent on the cloned origin. Thus, a DNA-unwinding enzyme other than the rep protein may be involved in the strand separation process accompanying replication which initiates at oriC in the M13 oriC chimeric DNAs and in the E. coli chromosome. The rep assay used for assessing the functionality of the cloned oriC is useful for analysis of any rep-independent origin of replication functional in E. coli. A direct selection for a cloned origin of replication is possible in the rep-3 recA56 host. Since the cloned origin is nonessential for propagation of the M13 chimeric phage in a rep+ host, mutations in the cloned origin may be constructed, and the mutant phage may be examined by a simple transductional analysis of the rep-3 recA56 mutant strain. PMID- 6257658 TI - Aerotaxis in Salmonella typhimurium: role of electron transport. AB - Sensory transduction in aerotaxis required electron transport, in contrast to chemotaxis, which is independent of electron transport. Assays for aerotaxis were developed by employing spatial and temporal oxygen gradients imposed independently of respiration. By varying the step increase in oxygen concentration in the temporal assay, the dose-response relationship was obtained for aerotaxis in Salmonella typhimurium. A half-maximal response at 0.4 microM oxygen and inhibition by 5 mM KCN suggested that the "receptor" for aerotaxis is cytochrome o. The response was independent of adenosine triphosphate formation via oxidative phosphorylation but did correlate with changes in membrane potential monitored with the fluorescent cyanine dye diS-C3-(5). Nitrate and fumarate, which are alternative electron acceptors for the respiratory chain in S. typhimurium, inhibited aerotaxis when nitrate reductase and fumarate reductase were induced. These results support the hypothesis that taxis to oxygen, nitrate, and fumarate is mediated by the electron transport system and by changes in the proton motive force. Aerotaxis was normal in Escherichia coli mutants that were defective in the tsr, tar, or trg genes; in S. typhimurium, oxygen did not stimulate methylation of the products of these genes. A cheC mutant which shows an inverse response to chemoattractants also gave an inverse response to oxygen. Therefore, aerotaxis is transduced by a distinct and unidentified signally protein but is focused into the common chemosensory pathway before the step involving the cheC product. When S. typhimurium became anaerobic, the decreased proton motive force from glycolysis supported slow swimming but not tumbling, indicating that a minimum proton motive force was required for tumbling. The bacteria rapidly adapted to the anaerobic condition and resumed tumbling after about 3 min. The adaptation period was much shorter when the bacteria had been previously grown anaerobically. PMID- 6257659 TI - Effect of Cibacron Blue F3GA on phosphoglycerate kinase of Lactobacillus plantarum and phosphoglycerate mutase of Leuconostoc dextranicum. AB - Blue dextran or Cibacron Blue F3GA has been shown to inhibit yeast phosphoglycerate kinase [EC 2.7.2.3] competitively with respect to ATP (Thompson et al. (1975) Proc. Natl. Acad. Sci. U.S. 72, 663--667; Beissner and Rudolph (1979) J. Biol. Chem. 254, 6273--6277). However, we have found that phosphoglycerate kinase of Lactobacillus plantarum was inhibited by Cibacron Blue F3GA, the blue chromophore of blue dextran, noncompetitively with respect to ATP, but competitively with respect to 3-phosphoglycerate. Further inhibition studies with Cibacron Blue F3GA suggest that one molecule of the dye was bound per molecule of phosphoglycerate kinase at a saturated level of either substrate, but two molecules of the dye were bound per molecule of the kinase with an unsaturated level of either substrate used as a fixed substrate. Furthermore, phosphoglycerate mutase [EC 2.7.5.3] of Leuconostoc dextranicum was also inhibited by Cibacron Blue F3GA competitively with respect to 3-phosphoglycerate and noncompetitively with respect to 2,3-bisphosphoglycerate. These results suggest that the 3-phosphoglycerate-binding site on both phosphoglycerate kinase and phosphoglycerate mutase can interact with Cibacron Blue F3GA. PMID- 6257661 TI - ESR studies on the membrane properties of a moderately halophilic bacterium. I. Physical properties of lipid bilayers in whole cells. AB - The lipid membrane properties of a moderately halophilic gram-negative bacterium, Pseudomonas halosaccharolytica ATCC 29423, were studied by the use of stearate spin labels, 5NS, 12NS, and 16NS, changing the temperature of ESR measurement from 15 to 50 degrees C. The order parameter and the rotational correlation time of the spin labels incorporated into intact cell membranes of this bacterium grown at various temperatures in media containing different NaCl concentrations were calculated. The activation energy of rotational microviscosity was obtained from Andrade plots. At low growth temperature and low NaCl concentration in the medium, extractable lipids of this bacterium contained comparatively large amounts of unsaturated fatty acids, but as the growth temperature and NaCl concentration in the medium increased, the contents of saturated and cyclopropanoic fatty acids increased to more than half of the total fatty acids. 5NS gave the highest order parameters for the intact cells of this bacterium, while 12NS gave lower and 16NS gave the lowest results. The order parameters of 5NS, 12NS, and 16NS were completely separated, and all order parameters decreased gradually as the measuring temperature was increased. In contrast, the rotational correlation times of the intact cells with 12NS were as large as those with 5NS, while those with 16NS were distinctly smaller. Increasing NaCl concentrations in the growth medium caused an increase of the rotational correlation times, that is, stiffened the lipid bilayers. The Andrade plot for 16NS was approximately a straight line, whereas 5NS and 12NS gave two straight lines crossing at a temperature near the growth temperature, indicating phase transition from solid to liquid. The microviscosity activation energies were 5--10 kcal/mol in the liquid phase and 15--25 kcal/mol in the solid phase. PMID- 6257662 TI - ESR studies on the membrane properties of a moderately halophilic bacterium. II. Effect of extreme growth conditions on liposome properties. AB - Lipid preparations from the cells of a moderately halophilic bacterium, Pseudomonas halosaccharolytica grown under the two extreme conditions of high temperature-high NaCl concentration and low temperature-low NaCl concentration showed distinctively different profiles in phospholipid and fatty acid composition. Cells grown at 40 degrees C in medium containing 3.5 M NaCl had high concentrations of saturated and C19 cyclopropanoic fatty acids (about 50 per cent of the total), whereas cells grown at 20 degrees C in medium containing 0.5 M NaCl had decreased concentrations of these fatty acids with increased concentrations of the corresponding unsaturated fatty acids. The phospholipid composition was also affected ty the culture conditions; cells grown at 40 degrees C in 3.5 M NaCl had large amounts of acidic phospholipids, whereas those grown at 20 degrees C in 0.5 M NaCl had small amounts. ESR studies on liposomes prepared from lipids of cells grown under the two conditions showed characteristic profiles for correlation times and order parameters of three spin labels of stearic acid derivatives similar to those of membranes of whole cells of this bacterium. ESR studies showed that the physical properties of the liposomes from the total extractable lipids and isolated phosphatidylglycerol from the cells were completely different from those of synthetic dioleoylphosphatidylglycerol. Liposomes of the lipids extracted from cells grown at 40 degrees C in 3.5 M NaCl showed change in rotational viscosity on altering the NaCl concentration to 0.5M, whereas liposomes of lipids extracted from cells grown at 20 degrees C in 0.5 M NaCl did not show change in rotational viscosity on increasing the NaCl concentration to 3.5 M. PMID- 6257660 TI - Heat production and proton release during the ATP-driven Ca uptake by fragmented sarcoplasmic reticulum from bullfrog and rabbit skeletal muscle. PMID- 6257663 TI - Carboxamidomethylation of a ribonuclease from Aspergillus saitoi. AB - 1) The inactivation of a RNase from Aspergillus saitoi (RNase Ms) was studied to obtain information on its active site. 2) Inactivation of RNase Ms by iodoacetamide was greater at an alkaline pH, and was protected more by 2',(3') AMP than by 2',(3')-GMP. 3) Analysis of the hydrolysis products with 6 N HCl and alkaline treatment of carboxamidomethylated RNase Ms showed that the sites of reaction were one carboxyl group and one histidine residue. 4) Since the incorporation of a carboxamidomethyl group into carboxylic acid was not protected by 2',(3')-AMP, it was concluded that the formation of N1 carboxamidomethylhistidine was responsible for the loss of enzymatic activity of RNase Ms. PMID- 6257664 TI - Binding of monovalent cations to Na+,K+-dependent ATPase purified from porcine kidney. I. Simultaneous binding of three sodium and two potassium or rubidium ions to the enzyme. AB - We previously measured the amounts of Na+ and K+ ions bound to the Na+,K+ dependent ATPase [EC 3.6.1.3] purified from porcine kidney by a modified membrane filtration method [(1979) J. Biochem. 86, 509--523]. In this study, we improved the method for measuring the amount of the active site and measured the amount of Rb+ ions (a K+ congener) bound to the ATPase as well as those of Na+ and K+ ions to get more accurate information on the K+- and Na+-binding sites. The following results were obtained. Two kinds of cation-binding sites were found to exist on the ATPase molecule. One was the Na+-binding sites (3 mol per mol of active site). Na+ ions were bound to the sites cooperatively (Hill coefficient, 2.5--3), and the apparent dissociation constant was 0.20--0.32 mM. Three moles of Na+ ions bound to the sites was displaced by 1 mol of K+ ions bound to the ATPase (phi K, 24 microM). The other was the K+-binding sites (2 mol per mol of active site). Two moles of K+, Rb+, or Na+ ions was bound to the sites cooperatively (Hill coefficient, 1.5--2), and their apparent dissociation constants were 0.044, 0.024, and 2.2 mM, respectively. We measured the amounts of Na+ and Rb+ ions bound to the ATPase in the presence of 0.8 mM NaCl and 0.13 mM RbCl, and obtained unequivocal evidence for the simultaneous binding of 3 mol of Na+ ions and 2 mol of Rb+ ions per mol of active site of the ATPase. PMID- 6257665 TI - Binding of monovalent cations to Na+,K+-dependent ATPase purified from porcine kidney. II. Acceleration of transition from a K+-bound form to a Na+-bound form by binding of ATP to a regulatory site of the enzyme. AB - Two kinds of ATP binding sites were found to exist on the ATPase molecule. One was the catalytic site (1 mol/mol phosphorylation site) and its apparent dissociation constant for ATP was about 1 microM. The other was the regulatory site(s) and its apparent dissociation constant for ATP was equal to or higher than about 0.2 mM. The affinities of both sites for AMPPNP were three times lower than those for ATP. The affinity of the ATPase for ATP was reduced by the addition of KCl, but unaffected by the addition of NaCl. As thermodynamically expected, the affinity of the Na+-binding sites for Na+ ions was almost completely unaffected by the addition of ATP, which markedly decreased that of the K+-binding sites for K+ and Rb+ ions. In the absence of KCl, Na+ ions were bound very rapidly to the Na+-binding sites [(1979) J. Biochem. 86, 509--523]. However, Na+ ions were bound very slowly to the enzyme preincubated with 50 microM KCl, and the Na+ binding was markedly accelerated by the addition of ATP or AMPPNP at concentrations much higher than several microM. On the other hand, in the presence of 50 microM KCl, 1 mol of ATP was bound to the catalytic site with the same dissociation constant as that in the absence of KCl, and another 1 mol of ATP bound with a dissociation constant of about 0.1 mM. Therefore, we concluded that the Na+ binding to the enzyme in a K+ form is markedly accelerated by the binding at ATP to the regulatory site. PMID- 6257666 TI - Binding of monovalent cations to Na+,K+-dependent ATPase purified from porcine kidney. III. Marked changes in affinities for monovalent cations induced by formation of an ADP-insensitive but no an ADP-Sensitive phosphoenzyme. AB - We measured the amounts of Rb+ ions (a K+ congener) as well as Na+ and K+ ions bound to the ATPase during the ATPase reaction at pH 7.5 and 0 degrees C. The affinity of the Na+-binding sites for three Na+ ions decreased markedly but that of the K+-binding sites for two K+ or Rb+ ions increased markedly upon formation of an ADP-insensitive phosphorylated intermediate. Furthermore, the present experiment did not give any indication of a change in the Hill coefficient of 2, and showed an increase in the affinity of the K+-binding sites for Rb+ ions of about 28 times upon the formation of an ADP-insensitive EP. The enzyme state with a high affinity for Rb+ was maintained after the disappearance of EP. When the ATPase was treated with N-ethylmaleimide (NEM), almost all the EP formed was ADP sensitive. The formation of an ADP-sensitive EP with the NEM-treated enzyme induced no change in the affinities of the ATPase for Na+ and Rb+ ions. PMID- 6257667 TI - Comparative studies on alveolar macrophages and polymorphonuclear leukocytes. III. Difference spectra of their cellular and subcellular fractions. AB - The respiratory pigments of rabbit polymorphonuclear leukocytes (PMN) and alveolar macrophages (A-MO) were compared in a spectrophotometric study conducted at liquid nitrogen temperature. In the difference spectra of the KCN-treated minus the untreated states and of the reduced minus the oxidized states, the cellular and granular fractions of PMN showed sharp absorption maxima identical with the absorption bands of myeloperoxidase (MPO). Even though A-MO revealed some guaiacol-peroxidation activity, the difference spectra of cellular and subcellular A-MO fractions did not show an MPO spectrum. The enzyme catalyzing the guaiacol peroxidation by A-MO appears to be an enzyme other than the MPO found in PMN. Despite the absence of the MPO spectrum, the difference spectra of A-MO granules when measured with KCN, dithionite, and succinate showed characteristic absorption bands of mitochondrial cytochromes, in contrast to the difference spectra of PMN, which showed far smaller cytochrome absorption bands. The results obtained suggest that the phagocytic metabolism of rabbit A-MO depends on mitochondrial respiration for its energy supply. PMID- 6257668 TI - Thyroxine 5'-monodeiodinase activity in regenerating liver of triiodothyronine treated rats. AB - The effect of triiodothyronine (T3) on hepatic thyroxine (T4) 5'-monodeiodinase and the subcellular localization of the enzyme were examined in regenerating rat liver, because it seemed likely that the effect of T3 might be accentuated during liver regeneration. Five days after T3 treatment, the specific activity of the monodeiodinase in the microsomal fraction (105,000 X g pellet) of regenerating liver was increased to 207% of the control value. Lineweaver-Burk plots showed that the Vmax for T4 5'-monodeiodination was about 3 times greater in T3-treated rats than in controls, but that there was no difference between the two groups in the apparent Km value for T4. About 55% of the total enzyme activity was found in the endoplasmic reticulum (ER) of the liver of both controls and T3-treated rats. The subcellular distribution of the enzyme was similar to that of NADPH cytochrome c reductase (NADPH-cyt c reductase), a marker of the ER, but different from that of Na+,K+-ATPase, a marker of plasma membranes (PM). PMID- 6257669 TI - Further studies on the smooth-surfaced membranes isolated from rat brain. AB - The light and heavy smooth-surfaced membranes (LSM and HSM), which had densities corresponding to 1.08 M and 1.28 M sucrose, respectively, were isolated from rat brain and some of their biochemical properties were investigated. Both LSM and HSM showed high Na+,K+-ATPase activity and, in particular, in HSM the activity was four times (21.55 mumol/mg protein/h) higher than that of the brain homogenate. High 2',3'-cyclic nucleotide 3'-phosphodiesterase activity (293.4 mumol/mg protein/h) was characteristic of LSM. 5'-Nucleotidase and acetylcholinesterase activities were also higher in LSM than in HSM. SDS polyacrylamide gel electrophoresis showed that LSM and HSM had many protein component and that low molecular weight proteins such as proteolipid protein and basic protein were almost absent, in contrast with myelin and myelin-like membrane. GM1 ganglioside constituted the major class of total ganglioside in both LSM and HSM. These biochemical findings suggested that LSM is a membrane that has not previously been described, or a membrane fraction related to the oligodendroglial plasma membrane. PMID- 6257670 TI - Photodissociation of cytochrome oxidase-nitric oxide at low temperatures. AB - Spectrophotometric studies revealed the irreversible photodissociation of reduced cytochrome oxidase-nitric oxide (NO) at 5 K. The dissociated NO recombined as the sample temperature was raised, and the half-recombination temperature was 65 K. The photodissociation at 5K was also confirmed by a change in the EPR spectrum; that is, ferroheme a-NO signals at gx=2.09 and gm=2.006 were replaced by a new signal at gm=2.03, and this change was reversed at the temperature of liquid nitrogen. Comparison of such behavior with that of cytochrome oxidase-carbon monoxide led us to propose that on photodissociation of NO from heme iron, the NO was trapped specifically at a site near the heme iron producing a new paramagnetic species. Its identification will require further studies. PMID- 6257671 TI - Characterization of the cytoplasmic inclusion bodies of the spleens from patients with adult form Gaucher's disease. AB - The twisted tubular cytoplasmic inclusion bodies were isolated from spleens of four patients with adult form Gaucher's disease. The chemical composition of the CIB (cytoplasmic inclusion bodies) was as follows: proteins, 10%, cholesterol, 10%, phospholipids, 10%, glycolipids, 70%. More than 90% of glycolipids from CIB were glucosylceramide. The structural protein profile of these bodies was examined by SDS-polyacrylamide disc gel electrophoresis on a semimicro-scale (s PAGE). A similar protein composition which included two glycoproteins was found in all the four cases. The tubular structure of the bodies was changed to a small and round form by the treatment with 1 mM EDTA-Na2 which removed some structural proteins from the bodies. This indicated that some proteins might have an important role in maintaining the tubular structure of CIB. PMID- 6257673 TI - Isolation, characterization, and biosynthesis of Forssman antigen in human lung and lung carcinoma. AB - A glycolipid was isolated from normal lung and lung carcinoma tissues. This glycolipid was identified as the Forssman antigen of pentaglycosyl ceramide by means of chemical and immunological methods. The presence of this antigenic glycolipid was observed in all the tissues examined of adult and embryo lungs, and of lung tumors irrespective of histological type. The extracts of human lung and lung tumors were capable of catalyzing the synthesis of Forssman antigen from globoside. PMID- 6257672 TI - A saturation transfer electron spin resonance study on the break in the Arrhenius plot for the rotational motion of Ca2+-dependent adenosine triphosphatase molecules in purified and lipid-replaced preparations of rabbit skeletal muscle sarcoplasmic reticulum. AB - By means of saturation transfer electron spin resonance spectroscopy the rotational motion of spin-labeled Ca2+-dependent ATPase molecules has been investigated for three kinds of preparations of rabbit skeletal muscle sarcoplasmic reticulum: MacLennan's enzyme (purified ATPase preparation), DOPC- and egg PC-ATPase (purified ATPase preparations in which endogenous lipids are replaced with dioleoyl and egg yolk phosphatidylcholine, respectively). The rotational mobility of the enzyme in these preparations is somewhat lower than that in the intact membrane, probably due to the reduced amount of lipids. For all the preparations, however, the Arrhenius plot for rotational mobility showed a break at about 18 degrees C, the same temperature at which a break in the Arrhenius plot for Ca2+-ATPase activity occurs. This result provides further evidence that the break in the Arrhenius plot is not related to a lipid phase transition but to a change in the physical state of the Ca2+-ATPase molecule existing in fluid lipids. PMID- 6257674 TI - Identification of the active amino acid residue of the polypeptide of ATP dependent protein breakdown. AB - The heat-stable polypeptide of the ATP-dependent proteolytic system was previously found to form covalent conjugates with proteins and to be activated by ATP in an adenylylation mechanism. To identify the functional amino acid of the polypeptide, the activated residue was specifically labeled by the reductive cleavage of the intermediate with [3H]borohydride. Following acid hydrolysis, the reduced labeled derivative was found to be completely oxidizable by periodate with formation of [3H]formaldehyde, and was identified as ethanolamine by thin layer chromatography, electrophoresis, and amino acid analyzer chromatography. These results indicate that the activated amino acid residue of the polypeptide is COOH-terminal glycine. PMID- 6257675 TI - A potent peptide affinity reagent for the opiate receptor. AB - The synthesis and characterization of a novel enkephalin analogue, Tyr-D-Ala-Gly Phe-Leu-chloromethyl ketone, is described. The biological potency of the compound in various assays has been determined to be very high. The compound is an alkylating affinity reagent and irreversibly inactivates a defined population of enkephalin receptors in rat brain membrane preparations, as well as irreversibly inhibiting electrically stimulated contractions in the mouse vas deferens tissue preparation. PMID- 6257677 TI - Kinetics of unfolding and folding of horse heart ferricytochrome c with urea. AB - Kinetic data for the reversible folding and unfolding by urea of horse heart ferricytochrome c, in 0.05 M phosphate + 0.25 M Na2SO4 buffer, pH 7.0, in the region of the main denaturation transition, 4-9 M, are reported. Stopped flow technique and absorptivity at 695, 528, and 361 nm as the monitoring probes were used. The decay profiles in the region of the transition 6-7.2 M urea are adequately described by a rate law with two exponential decay terms, but a rate law with only a single term is found to be applicable at the lower and higher limits of the transition. The apparent rate constant for the fast phase exhibits urea dependence with a minimum value at about 6.5 M urea, while the apparent rate constant of the slow phase is found to be independent of urea and has a value of 0.04 +/- 0.02 s-1. The assignment of the two apparent rate constants to the respective steps and the characterization of the processes involved were carried out through correlation of the kinetic data to the results from equilibrium studies for urea denaturation ( Myer, Y. P., MacDonald, L. H., Verma, B. C., and Pande, A. (1980) Biochemistry 19, 199-207). A mechanism X1 in equilibrium X2 in equilibrium D, where the first step is the urea-dependent unfolding and folding, and the second, an apparent urea-independent process involving possibly reorganization of the unfolded form X2, has been proposed to account for the above findings. The X2 in equilibrium D process is further considered in light of various possibilities: the incorrect folding of the unfolded form, the alteration of heme iron coordination, and the cis-trans isomerization of proline. PMID- 6257676 TI - Guanine nucleotides inhibit binding of agonists and antagonists to soluble opiate receptors. AB - The guanine nucleotides GDP, GTP, and guanosine-5'-(beta, gamma imido)triphosphate inhibit binding of opiates and opioid peptides to receptors solubilized from membranes of neuroblastoma X glioma NG108-15 hybrid cells. The inhibition reflects decreased affinity of receptors for opioid ligands. Whereas in membranes, only opioid agonist binding is sensitive to guanine nucleotide inhibition, both agonist and antagonist binding is reduced in the case of soluble receptors. Furthermore, soluble receptors are more sensitive to the effects of guanine nucleotides than are membrane-bound receptors. These observations are consistent with the suggestion that solubilized receptors may be complexes of an opiate binding protein and a guanine nucleotide-sensitive regulatory component. PMID- 6257678 TI - The reversal of the Gpp(NH)p-activated state of adenylate cyclase by GTP and hormone is by the "collision coupling" mechanism. AB - The guanylyl imidodiphosphate-activated state of turkey erythrocyte cyclase can be reversed to the basal state by the simultaneous action of beta-agonists and GTP. The rate of reversal diminishes progressively with decreasing concentration of beta-adrenergic receptors on the membrane surface, whereas the extent of reversal is always maximal. The rate of reversal is found to be linearly dependent on the concentration of beta-adrenergic receptors within the membranes. This result supports the notion that the interaction of the enzyme unit and the beta-adrenergic receptor is catalytic and therefore of the "collision coupling" type. The dependence of the rate of reversal reaction on epinephrine concentration is noncooperative with an apparent dissociation constant of KD = 3.0 X 10(-6) M. The fraction of guanylyl imidodiphosphate-activated cyclase system which can be reversed by GTP and a beta-agonist strongly depends on temperature and reveals a sharp transition at 24 degrees C which is the freezing temperature of the inner monolayer. It is suggested that the GTP regulatory unit is inactive when the inner monolayer is frozen. PMID- 6257679 TI - Role of insulin, glucose, and cyclic GMP in the regulation of glucokinase in cultured hepatocytes. AB - Following insulin addition to the medium of primary cultures of hepatocytes, the activity of glucokinase increased by 50% during the first 4 h, remained constant for an additional 2 to 3 h, and was followed by a second increase in activity. This biphasic increase in activity was a reflection of the amount of glucokinase enzyme protein present as measured by quantitative immunoprecipitation. The level of cGMP was found to increase sharply 6 h following the addition of insulin and just prior to the second phase of the increase in glucokinase activity. When hepatocytes were cultured in the absence of carbohydrates, only the initial phase of the increase in enzyme activity in response to insulin was observed, and no increase in the level of cGMP was found. However, the addition of 8-bromo-cGMP to the culture medium at 6 h or later could restore the second increase in activity. The addition to the medium of glucose, fructose, pyruvate, or lactate enhanced the insulin-induced increase in glucokinase, but only fructose, pyruvate, and lactate increased the activity of the enzyme in the absence of insulin. When the phosphorylation of hexoses was blocked by the addition of N-acetylglucosamine to the culture medium, an intermediate level of glucokinase activity was observed in response to insulin. The full response was restored by the inclusion of 8-bromo cGMP in the medium. Both phases of the increase in glucokinase activity were inhibited by cycloheximide, whereas the addition to the culture medium of cordycepin or actinomycin D prevented only the initial increase in activity and not the second increase, which arose from the addition of 8-bromo-cGMP to the cultures. PMID- 6257681 TI - Use of specific lysine modifications to identify the site of reaction between cytochrome c and ferricyanide. AB - The site of the reaction between horse heart ferrocytochrome c and ferricyanide was investigated by measuring the reaction rate of cytochrome c derivatives specifically modified at single lysine residues to form trifluoroacetyl or trifluoromethylphenylcarbamyl amino groups. Cytochrome c derivatives singly modified at lysines 8, 13, 25, 27, 72, 79, and 87 surrounding the heme crevice had rate constants decreased from that of native cytochrome c by factors of 1.29, 2.03, 1.12, 1.35, 1.46, 1.29, and 1.19, respectively. Modification of a given lysine with the bulky trifluoromethylphenylcarbamyl group caused nearly the same decrease in reaction rate as modification with the trifluoroacetyl group, indicating that the effect was due to removal of an electrostatic interaction between the protonated lysine amino group and ferricyanide. Modification of lysines 22, 55, 99, and 100 at the right side, bottom, and back of cytochrome c had no effect on the reaction rate. These results indicate that the reaction site is located at the exposed edge of the heme and that the electrostatic interaction between ferricyanide and cytochrome c is dominated by the lysine amino groups surrounding the heme crevice, which include lysine 86, in addition to the ones listed above. We have used the specific lysine modification results to estimate the contribution of each lysine amino group to the electrostatic interaction and have developed a semiempirical relation for the total electrostatic interaction. PMID- 6257680 TI - Phase separation of integral membrane proteins in Triton X-114 solution. AB - A solution of the nonionic detergent Triton X-114 is homogeneous at 0 degrees C but separates in an aqueous phase and a detergent phase above 20 degrees C. The extent of this detergent phase separation increases with the temperature and is sensitive to the presence of other surfactants. The partition of proteins during phase separation in solutions of Triton X-114 is investigated. Hydrophilic proteins are found exclusively in the aqueous phase, and integral membrane proteins with an amphiphilic nature are recovered in the detergent phase. Triton X-114 is used to solubilize membranes and whole cells, and the soluble material is submitted to phase separation. Integral membrane proteins can thus be separated from hydrophilic proteins and identified as such in crude membrane or cellular detergent extracts. PMID- 6257682 TI - Purification and properties of an endodeoxyribonuclease from nuclei of bovine small intestinal mucosa. AB - An endodeoxyribonuclease has been purified from nuclei of bovine small intestinal mucosa to a homogeneous state by a procedure involving affinity chromatography on heparin-agarose. The endonuclease, which was found to be bound to chromatin, has a pH optimum of 5.4. It requires Mn2+ or Co2+ for activity and its maximum activity with Mg2+ is about 80% of that with Mn2+. Its activity is strongly inhibited by sulfhydryl-blocking agents, and by ethidium bromide. The enzyme does not attack RNA and is inhibited by it. Its isoelectric point is 8.5 +/- 0.1, and its molecular weight is 49,000 +/- 3,000, determined by sucrose gradient sedimentation and gel filtration on Sephadex G-100. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate indicated that the enzyme is composed of two nonidentical subunits with molecular weights of 30,000 and 23,000. The enzyme catalyzes the endonucleolytic cleavage of circular duplex ColE1 DNA via single strand scissions from the initial stage of degradation. The average size of the limit products of native phage T7 or ColE1 DNA is about 2,000 to 1,500 base pairs, estimated by neutral sucrose gradient sedimentation or agarose gel electrophoresis. The enzyme degrades denatured DNA about 20 times faster than native DNA. The products contain 5'-phosphoryl and 3'-hydroxyl termini, and all four deoxymononucleotides are present in almost equal amounts at the 5'-termini. PMID- 6257683 TI - The effects of copper depletion on cytochrome c oxidase. PMID- 6257684 TI - Regulation of cyclic nucleotide-dependent protein kinase activity by histones and poly(L-arginine). AB - Interaction of cGMP-dependent protein kinase with histones H2A, H2B, H3, and H4, or poly(L-arginine) resulted in changes in enzyme conformation such that inactivation of cGMP binding and activation of basal catalytic activity (assayed without cGMP) occurred. Total kinase activity as determined by phosphorylation of exogenous substrates subsequently decreased, but autophosphorylation of the enzyme was enhanced. The reaction was specific for nucleosome core histones and poly(L-arginine); H1, troponin, and poly(L-lysine) had no effect. Inactivation of cyclic nucleotide binding sites followed pseudo-first order kinetics and, at various histone concentrations, exhibited saturation kinetics at low ionic strength (2 mM potassium phosphate, pH 6.8), but non-saturation kinetics at higher ionic strength (37.5 mM potassium phosphate, pH 6.8, 12.5 mM MgCl2). Saturation kinetics was observed with poly(L-arginine) at both low and high ionic strength. Kinetic parameters measured under saturation conditions were determined for each core histone and poly(L-arginine). Core histones and poly(L-arginine) were noncompetitive inhibitors of cGMP binding; core histones and poly(L arginine) interacted competitively at an enzyme site designated as the poly(L arginine) binding site. Regulatory subunits of cAMP-dependent protein kinase contain a similar poly(L-arginine) binding site. Modulator proteins bind to poly(L-arginine) or arginyl residues in histone to prevent interaction with the poly(L-arginine) binding site on the enzymes. Through this mechanism, modulator proteins maintain cyclic nucleotide dependency and full enzyme activity. PMID- 6257685 TI - A hypersensitivity of glycogen phosphorylase activation in hearts of diabetic rats. AB - This study was initiated to determine whether glycogen phosphorylase activation was defective in hearts of alloxan diabetic rats. When hearts were perfused by gravity flow for 1 to 10 min with various concentrations of epinephrine, activation of glycogen phosphorylase in the diabetic was significantly greater at every time and epinephrine concentration than that seen in the normal. Cyclic AMP accumulation and protein kinase activation by epinephrine in the diabetic were not appreciably different or were lower than the normal responses to the hormone. The effects of epinephrine on cAMP and protein kinase were blocked in both normal and diabetic hearts by propranolol. While the beta blocker prevented phosphorylase activation in the normal hearts, it did not block phosphorylase activation by epinephrine in the diabetic hearts. Likewise, the alpha agonist phenylephrine activated phosphorylase in the diabetic but not in the normal hearts. While glucagon produced the same phosphorylase hypersensitivity in diabetic hearts, the cAMP and protein kinase responses were not altered by diabetes. Phosphorylase phosphatase activity was found to be unaltered by either epinephrine or diabetes, whereas phosphorylase kinase activation by epinephrine in the diabetic was double the normal response. These data are consistent with a diabetes-related unmasking of an alpha effect on cardiac phosphorylase activation and an unexplained increase in the sensitivity of phosphorylase kinase activation by protein kinase. PMID- 6257686 TI - Primary structure of the bacteriophage T4 DNA helix-destabilizing protein. AB - The amino acid sequence of the single-stranded DNA-binding protein encoded by gene 32 of bacteriophage T4 has been determined by manual and automated sequencing of peptides derived from cyanogen bromide cleavage and digestion with trypsin, chymotrypsin, and staphylococcal protease. Tryptic digestion of citraconylated or succinylated gene 32 protein yields five peptides containing 4, 27, 42, 65, and 163 residues, respectively, which can be separated by Sephadex chromatography. Each of these tryptic peptides was subjected to automated sequencing and, if necessary, more extensive cleavage. The gene 32 protein contains 301 amino acids and has a molecular weight of 33,487. Based on its primary structure, the gene 32 protein is predicted to contain 36% alpha helix, 18% beta sheet, and 46% random coil. The native protein can be specifically cleaved at lysine 21 and 253 by limited trypsin digestion. Previous studies have shown that the "B" region (residues 1 to 21) is essential for cooperative binding to single-stranded DNA. The "A" region (residues 254 to 301) has been implicated in controlling the helix-destabilizing "activity" of gene 32 protein and in interacting with other T4 DNA replication proteins. The "A" region has a net charge of -10 and, in addition, contains two unusual stretches of 4 serine residues separated by glycine 284. The region between positions 72 and 116 contains 6 of the 8 tyrosine residues in the protein and may be important for DNA binding. PMID- 6257687 TI - (Na+ + K+)-stimulated ATPase inhibition by cesalin and macromomycin. AB - (Na+ + K+)-stimulated ATPase was purified from dog kidney and its catalytic and glycoprotein subunits were separated. The enzymatic activity of the ATPase was totally inhibited by ouabain and partially inhibited by cesalin, maromomycin, concanavalin A, and wheat germ agglutinin. The inhibitions by cesalin or macromomycin can be reversed by the addition of phosphatidylethanolamine or phosphatidylserine, but not phosphatidylcholine. The specific binding of 125I cesalin to the enzyme was inhibited by concanavalin A, wheat germ agglutinin, macromomycin, and the antibodies prepared in rabbits against the holoenzyme and the glycoprotein subunit, but not by ouabain, simple sugars, or the antibody against the catalytic subunit. It is proposed that the antitumor activities of cesalin and macromomycin are initiated in part by their binding to the glycoprotein subunit of (Na+ + K+)-ATPase in the plasma membrane. PMID- 6257688 TI - Inhibition of phosphoribosylpyrophosphate synthesis in human fibroblasts by 6 methylthioinosinate. PMID- 6257689 TI - Interaction of calmodulin with histones. Alteration of histone dephosphorylation. AB - The Ca2+-dependent regulator protein (CDR), also frequently termed "calmodulin" was determined to influence the dephosphorylation of mixed calf thymus histones or purified histones 1, 2A, or 2B by a partially purified bovine brain phosphoprotein phosphatase. CDR increase the rate of dephosphorylation of mixed histones more than 20-fold. With increasing concentrations of mixed histones as substrate, a proportionate increase of CDR concentration was required to maintain maximal expression of histone phosphatase activity. Mixed histones suppressed the activation by CDR of a bovine brain cyclic nucleotide phosphodiesterase activity, with activation being restored by increased quantities of CDR. Dephosphorylation of casein and phosphorylase alpha by the phosphatase preparation was not affected by CDR. These observations support the interpretation that the effects of CDR on histone dephosphorylation are substrate-directed. The rates of dephosphorylation of histones 1, 2A, and 2B by the phosphatase were 4- to 12-fold more rapid at low (sub-micromolar) concentrations of free Ca2+ than at high (200 microM) Ca2+ in incubations containing CDR, but they were unaffected by Ca2+ in incubations without CDR. The addition of stoichiometric quantities of calmodulin increased the apparent Km of the phosphatase for the various histones 2- to 6-fold, while maximal velocities were 4- to 12-fold higher at low than at high added Ca2+. The inhibitory effect of Ca2+ on histone dephosphorylation was immediately reversible by chelation of Ca2+ with EDTA. Ca2+-dependent inhibition of histone 1 or 2B phosphatase activities was also produced by rabbit skeletal muscle troponin C, but not by rabbit skeletal muscle parvalbumin, by poly(L-aspartate) or poly(L glutamate). The phosphorylated fragment from the NH2-terminal region of either H2A (generated by treatment with N-bromosuccinimide) or H2B (generated by treatment with cyanogen bromide) was dephosphorylated by the phosphatase, with the rates of dephosphorylation being reduced 3- to 6-fold by Ca2+ in incubations containing CDR. PMID- 6257690 TI - Cardiolipin requirement for electron transfer in complex I and III of the mitochondrial respiratory chain. AB - Almost complete phospholipid depletion has been achieved for Complex I and III of the mitochondrial respiratory chain using a technique that involves elution on Sephadex LH-20 in the presence of Triton X-100. Enzymic activity may be regenerated by replenishment with phospholipid. However, restoration of enzymic activity in phospholipid-depleted Complex I and III has been shown to require the presence of cardiolipin. These results are, therefore, similar to findings on the absolute catalytic requirement of cardiolipin for cytochrome oxidase activity (Fry, M., and Green, D. E. (1980) Biochem. Biophys. Res. Commun. 93, 1238-1246). At least two roles for phospholipid involvement in electron transfer processes are proposed, a catalytic role provided specifically by cardiolipin and a dispersive role that may be provided by various phospholipids or detergents. The absolute requirement of enzymic activity for cardiolipin suggests that this phospholipid plays a crucial role in the coupled electron transfer process. PMID- 6257691 TI - Functional inactivation of lac alpha-peptide mRNA by a factor that purifies that Escherichia coli RNase III. AB - Using RNA-directed synthesis of the alpha-peptide of beta-galactosidase as an assay, a factor was purified that inactivated further function of the mRNA. In the presence of Ca2+ ions to inhibit most nuclease activity, inactivation of mRNA occurred during incubation with ribosomes or with a 1 M KCl wash of ribosomes. The inactivation activity required Mg2+ ions, and purified as a single factor which did not bind to DEAE-cellulose, but bound reversibly to phosphocellulose. The factor eluted from Sephadex G-150 with an apparent molecular weight of about 43,000. Purified 700-fold, it showed no detectable exonuclease activity, and little or no cleavage of a variety of single-stranded substrates, including full length lac operon mRNA; but repurified inactivated mRNA was still inactive for protein synthesis. The factor did not inhibit poly(U)-directed polyphenylalanine synthesis. When proteins isolated from the ribosomal wash were individually tested, highly purified RNase III, which purifies in the same way and has the same size, also inactivated lac mRNA. The ribosomal wash from an RNase III- strain showed little if any activity compared to that from an isogenic RNase III+ strain. The possibility of a site-specific inactivating cleavage of mRNA by RNase III at or near the 5' end is considered. PMID- 6257692 TI - Spatial proximity of two divalent metal ions at the active site of S adenosylmethionine synthetase. AB - S-Adenosylmethionine synthetase from Escherichia coli is shown to require 2 divalent metal ions/enzyme subunit for maximal enzymatic activity. In the absence of substrate, the tetrameric enzyme binds 1 Mn(II) ion/subunit, whereas in the presence of a nucleotide substrate, adenylylimidodiphosphate, or the product pyrophosphate, there are two Mn(II)-binding sites/subunit. Electron paramagnetic resonance spectra of Mn(II) bound to the enzyme reveal a spin exchange interaction between 2 Mn(II) ions in complexes of enzyme and Mn(II) which also contain adenosylmethionine, K+, and either pyrophosphate or imidotriphosphate. Since a spin exchange interaction requires orbital overlap between the 2 ions, the metal ions must be bound close to one another, and they may share a common ligand. PMID- 6257693 TI - Superoxide dismutase. Examination of the metal binding sites by electron spin echo spectroscopy. PMID- 6257694 TI - Localization of a dolichyl phosphate phosphatase in plasma membranes of rat liver. PMID- 6257695 TI - The effects of phospholipids on the properties of hepatic 5'-nucleotidase. AB - Arrhenius plots of 5'-nucleotidase activity in microsomes or plasma membranes from rat liver exhibited transitions at approximately 35 degrees C. The enzyme was purified from homogenates after solubilization in 2% Triton X-100 and 1% sodium deoxycholate. After the initial steps of the purification, the enzyme was recovered in membranes, as judged by both thin section and freeze-fracture electron microscopy, which contained sphingomyelin, phosphatidylcholine, and phosphatidylethanolamine. The purest fractions of 5'-nucleotidase were enriched approximate 3,000-fold, consisted of similar membranes, but only contained sphingomyelin. Thermal transitions were detected in Arrhenius plots of 5' nucleotidase after detergent solubilization, in the membranes which contained the three phospholipids, but not in the purified fraction which contained only sphingomyelin; transitions were also detected after reassociation of the purified enzyme with microsomal or plasma membrane lipids and phosphatidylcholine but not with phosphatidylethanolamine. Phosphatidylcholines containing specific fatty acids all affected the energy of activation of 5'-nucleotidase, and the detergent Sarkosyl, which has been shown to dissociate phospholipids from 5'-nucleotidase (Evans, W. H., and Gurd, J. W. (1973) Biochem. J. 133, 189-199), caused a marked decrease in the stability of the enzyme to heating. Inhibition of 5'-nucleotidase by concanavalin A followed by reactivation with alpha-methyl-D-mannoside resulted in linear Arrhenius plots of 5'-nucleotidase activity in membrane fractions, and in lower transition temperatures for the detergent, solubilized enzyme. It is concluded that in situ, 5'-nucleotidase interacts with both sphingomyelin and phosphatidylcholine; the first apparently influences the stability of the enzyme and the second, the energy of activation. In addition, the lipid environment of the enzyme seems to be altered as a result of lectin binding. PMID- 6257696 TI - The leftward promoter of bacteriophage lambda. Isolation on a small restriction fragment and deletion of adjacent regions. AB - As part of our investigations on the relationship between DNA structure and gene regulation, a 352-base pair Hae III fragment was cloned containing the leftward operator-promoter (PL) region of bacteriophage lambda. This was accomplished without the aid of a phenotypic assay for the cloned fragment. A Hae III digest of a segment of the lambda genome was first fractionated by RPC-5 column chromatography. The partially purified PL fragment was then ligated into the Eco RI site of the pBR322 plasmid vector and cloned into the recBC+ Escherichia coli host C600(R-M-) using a technique that converts the Hae III ends of the fragment into Eco RI sites. Similar cloning attempts into a recBC- host (C600-SF8) were unsuccessful. The cloned fragment has the PL promoter oriented toward the tetracycline resistance genes of the vector, and is isolated from the plasmid (pRW601) by digestion with Eco RI followed by sucrose gradient sedimentation. The fragment was identified as PL by restriction mapping, repressor binding, sequencing, and promoter location. The now complete sequence of this fragment, part of which was known previously, reveals a large A/T-rich region immediately adjacent to the PL promoter. We have generated deletions in this region in order to study the influence of this sequence on promoter function. PMID- 6257697 TI - Mossbauer spectroscopic studies of Escherichia coli sulfite reductase. Evidence for coupling between the siroheme and Fe4S4 cluster prosthetic groups. AB - Escherichia coli NADPH-sulfite reductase is a complex hemoflavoprotein with an alpha 8 beta 4 subunit structure. The beta-subunits each contain one siroheme and a tetranuclear iron-sulfur center (Fe4S4). Isolated beta-monomers can catalyze the 6-electron reduction of sulfite to sulfide. We have studied the beta-monomers with Mossbauer and EPR spectroscopy. The data show conclusively that the siroheme and the Fe4S4 cluster are strongly exchange-coupled. This is proven by the observations that (a) the two chromophores share a single electronic spin and (b) the addition of 1 electron to oxidized sulfite reductase changes the environments of 5 iron atoms. Spin-sharing is demonstrated in oxidized and 2-electron-reduced sulfite reductase and strongly implicated in 1-electron-reduced material. Thus, sulfite reductase provides the first example of an active site where a heme and an iron-sulfur cluster are closely linked as a functional unit, probably via a common bridging ligand. PMID- 6257698 TI - Isolation of Escherichia coli mutants with elevated levels of membrane enzymes. A trans-acting mutation controlling diglyceride kinase. AB - We have developed a rapid autoradiographic colony assay for detecting mutants with elevated levels of certain biosynthetic enzymes. Four Escherichia coli strains in which the specific activity of the membrane enzyme diglyceride kinase is increased 5-10-fold have been obtained with this approach. The mutant kinase has the same thermal denaturation profile and subcellular localization as the wild type. Five other membrane enzymes involved in phospholipid bilayer assembly are unaffected. In one of these strains (GK-1) the mutation (dgkR-1) responsible for the elevated kinase has been mapped at a new site near minute 92, while the previously identified structural gene (dgk) lies near minute 90. When the structural gene for the kinase (dgk) is cloned on a multi-copy vector-like ColE1, the kinase can be overproduced 5-10-fold on the basis of gene dosage (Lightner, V. A., Larson, T. J., Tailleur, P., Kantor, G. D., Raetz, C. R. H., Bell, R. M., and Modrich, P. (1980) J. Biol. Chem. 255, 9413-9420). Introduction of such hybrid plasmids into a mutant harboring dgkR-1 leads to a multiplicative (rather than additive) effect, resulting in specific activities of diglyceride kinase that are 35-75-fold higher than normal. These results show that dgkR-1 is a trans acting mutation and suggest the existence of novel regulatory proteins (or metabolites) that direct the expression of certain membrane enzymes. PMID- 6257699 TI - Electron-nuclear double resonance of horseradish peroxidase compound I. Detection of the porphyrin pi-cation radical. AB - Electron-nuclear double resonance spectra of horseradish peroxidase Compound I exhibit resonances from 14N and beta-protons, and most probably alpha-protons as well. The measurements prove that the oxyferryl iron of this enzymic intermediate is spin-coupled to a porphyrin radical. Comparison of experimentally obtained average pi-electron spin densities with theoretical predictions for a 4-fold symmetric porphyrin pi-cation radical is supportive of a 2A2u assignment for the radical's electronic state. PMID- 6257701 TI - DNA sequences of structural genes for Eco RI DNA restriction and modification enzymes. PMID- 6257700 TI - Affinity labeling of multiplication stimulating activity receptors in membranes from rat and human tissues. AB - Plasma membranes from rat adipocytes and liver and from human placenta have been labeled by covalent cross-linking to membrane-bound 125I-labeled multiplication stimulating activity (125I-MSA) with three different bishydroxysuccinimide esters: disuccinimidyl suberate, disuccinimidyl succinate, and ethyleneglycolyl bis(succinimidyl succinate). Dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiographic analysis of the 125I-MSA-labeled material in the presence of dithiothreitol reveals one single-labeled protein migrating with an apparent Mr = 255,000 regardless of the kind and concentration of cross-linker used. Electrophoresis in the absence of reductant indicates that the affinity-labeled species is not disulfide-linked to any other protein in the native plasma membrane, but contains internal disulfide bonds that compact its structure. The labeling of the Mr = 255,000 species increases with increasing concentrations of 125I-MSA between 0.3 and 3 nM. Labeling is abolished in a competitive manner by nonradioactive MSA but not by similar concentrations of insulin, proinsulin, or epidermal growth factor in all three tissues examined. The unique labeling of this Mr = 225,000 membrane component and its selective inhibition by MSA suggest that this protein is a plasma membrane receptor for MSA. PMID- 6257702 TI - Partial NH2- and cooh-terminal sequence analyses of Eco RI DNA restriction and modification enzymes. AB - NH2- and COOH-terminal amino acid sequences of the Eco RI restriction and modification enzymes have been determined. The results allow localization of the coding regions within the DNA segment which controls activity of both enzymes. Processing of the endonuclease is limited to removal of NH2-terminal formylmethionine whereas, in the case of the methylase, formylMet-Ala is removed. PMID- 6257704 TI - Limitations in the conventional analysis of the interaction of triiodothyronine with solubilized nuclear receptor sites. Inapparent binding of triiodothyronine to nonspecific binding sites. PMID- 6257703 TI - Sequence analysis of the DNA encoding the Eco RI endonuclease and methylase. AB - The Eco RI endonuclease and methylase recognize the same hexanucleotide substrate sequence. We have determined the sequence of a fragment of DNA which encodes these enzymes using the chain-termination method of Sanger (Sanger, F., Nicklen, S., and Coulson, A. R. (1977) Proc. Natl. Acad. Sci. U. S. A. 74, 5463-5467). The amino acid sequences of both enzymes were derived from the DNA sequence. The coding regions selected include the only open translational frames of sufficient length to accommodate the enzymes. They coincide with previously established gene boundaries and orientation. The predicted amino acid sequences correlate well with analyses of the purified protein. Comparison of the nucleotide and protein sequences reveals no homology between the endonuclease and methylase which might provide insight into the origin of the restriction-modification system or the mechanism of common substrate recognition. Based on secondary structure predictions, the two enzymes also have grossly different molecular architecture. The base composition of the sequence is 65% A + T, and the codon usage is significantly different from that observed in several Escherichia coli chromosomal genes. In some cases, frequently selected codons are recognized by minor tRNA species. A spontaneous mutation in the endonuclease gene was isolated. Serine replaces arginine at residue 187. In crude extracts, Eco RI specific cleavage is approximately 0.3% wild type. PMID- 6257705 TI - Comparison of the lipoprotein gene among the Enterobacteriaceae. DNA sequence of Erwinia amylovora lipoprotein gene. AB - A DNA sequence of 816 base pairs encompassing the entire Erwinia amylovora lipoprotein gene was determined. Sequence comparison between E. amylovora, Escherichia coli, and Serratia marcescens suggests that the structure of the lipoprotein has been highly conserved under the constraint of efficient gene expression selecting promoter structure, mRNA secondary structure, and codon usage in addition to the polypeptide function. The sequence also suggests that the lpp gene of the three bacteria diverged sequentially in the course of evolution. PMID- 6257706 TI - Proton magnetic resonance relaxation in Pseudomonas aeruginosa cytochrome oxidase solutions. AB - We have measured the temperature and frequency dependence of solvent proton magnetic relaxation rates in solutions of Pseudomonas aeruginosa cytochrome oxidase (EC 1.9.3.2) in its native low spin oxidized, its reduced, and its carbonyl reduced derivative. In solutions of the native oxidized enzyme, a large paramagnetic enhancement of the proton NMR relaxation rates, propagated to the solvent by the fast exchange mechanism, is observed. The ratio (T1/T2)pmg = 1.25 +/- 0.10 at 24 MHz demonstrates that dipole-dipole interaction of the neighboring paramagnets is the dominant relaxation mechanism. Measurements of proton relaxation in solutions of cytochrome oxidase from which the hemes D have been extracted demonstrates that hemes C do not contribute to the observed paramagnetic effects. The electron spin relaxation time of the ferric hemes D of 3.2 +/- 0.4 ns is calculated from the frequency dispersion data. This is the longest value reported for hemoprotein solutions so far. These features of a low spin ferric hemoprotein are similar to those found recently both for the microbial and for the microsomal cytochrome P-450. The calculated distances between the exchanging proton(s) and heme D iron ions demonstrate the high accessibility of the environment of heme D from the solvent side, also for molecules not penetrating the inner coordination sphere. PMID- 6257707 TI - Magnetic interactions between dysprosium complexes and two soluble iron-sulfur proteins. AB - A tetranuclear ferredoxin from Rhodopseudomonas gelatinosa [4Fe-4S](+2,+3) has been examined by electron paramagnetic resonance techniques. The temperature dependence and relaxation characteristics of the spectral lines indicate that the spin-lattice interaction is described at low temperatures by a T2 law which gives way to a T9 Raman relaxation as the temperature is raised. At higher temperatures an Orbach process becomes dominant. In the presence of dysprosium complexes the relaxation and line widths are modified. From crystallographic structure determinations of similar proteins we are able to relate the dysprosium effects to the spatial separation between the complex and the tetranuclear cluster. This scale is then tested against a ferredoxin from Clostridium pasteurianum which contains two tetranuclear clusters, [4Fe-4S](+1,+2). We find that for these soluble iron-sulfur proteins the dysprosium complexes form a shell at the protein surface. The magnetic interaction between the clusters and the complexes altering the relaxation time goes as r-6, while the low temperature line broadening is described by an r-3 dipole interaction. PMID- 6257708 TI - Correlation of beta-adrenergic receptor-stimulated [3H]GDP release and adenylate cyclase activation. Differences between frog and turkey erythrocyte membranes. PMID- 6257710 TI - Cloning of genes involved in membrane lipid synthesis. Effects of amplification of phosphatidylserine synthase in Escherichia coli. PMID- 6257709 TI - Stimulation of Rb+ transport by glucagon in isolated rat hepatocytes. AB - Glucagon caused a 2-2.5-fold increase in 86Rb+ (a K+ tracer) uptake in primary monolayers of rat hepatocytes. Removal of the hormone led to a slow reversal of the effect over a period of hours. Glucagon acted by increasing the maximum velocity of influx. Ouabain inhibited Rb+ uptake in both hormone-induced and control cells by 85-90%. Hormone stimulation and ouabain inhibition did not affect exit. The induction by glucagon required 3-4 h for full expression and was dependent on protein synthesis and changes in cAMP. Half-maximum stimulation occurred at a concentration of 0.4 nM of the hormone. The ionophores monensin and gramicidin, which lead to Na+ influx, stimulated ouabain-sensitive Rb+ transport. This suggested that the (Na,K)-pump rate is limited by the internal Na+ concentration in both glucagon-stimulated and control cells. PMID- 6257711 TI - Sodium-dependent activation of sea urchin spermatozoa by speract and monensin. PMID- 6257712 TI - Human serum albumin: binding specificity and allosteric effect of parinarate and stearate. A dianionic spin label study. PMID- 6257713 TI - Rapid reduction of cytochrome c1 in the presence of antimycin and its implication for the mechanism of electron transfer in the cytochrome b-c1 segment of the mitochondrial respiratory chain. AB - Antimycin, a specific and highly potent inhibitor of electron transfer in the cytochrome b-c1 segment of the mitochondrial respiratory chain, does not inhibit reduction of cytochrome c1 by succinate in isolated succinate-cytochrome c reductase complex under conditions where the respiratory chain complex undergoes one oxidation-reduction turnover. If a slight molar excess of cytochrome c is added to the isolated reductase complex in the presence of antimycin, there is rapid reduction of one equivalent of c type cytochrome by succinate, after which reduction of the remaining c type cytochrome is inhibited. Antimycin fully inhibits succinate-cytochrome c reductase activity of isolated succinate cytochrome c reductase complex in which the b-c1 complex undergoes multiple turnovers in a catalytic fashion. In addition, when antimycin is added to isolated reductase complex in the presence of cytochrome c plus cytochrome c oxidase, the inhibitor causes a "crossover" in the steady state level of reduction of the cytochromes b and c1 comparable to this classical effect in mitochondria. On the basis of these results, it is suggested that linear schemes of electron transfer are not adequate to account for the site of antimycin inhibition and the mechanism of electron transfer in the cytochrome b-c1 segment of the respiratory chain. The effects of antimycin are consistent with cyclic electron transfer mechanisms such as the protonmotive Q cycle. PMID- 6257714 TI - Cloning of the yeast methionyl-tRNA synthetase gene. AB - A pool of random wild type yeast DNA fragments obtained by partial Sau IIIA restriction enzyme digestion and inserted in the Bam HI site of the hybrid yeast Escherichia coli plasmid ((pFL1) has been used to transform to prototrophy a methionyl-tRNA synthetase-impaired mutant requiring methionine. In the numerous prototroph strains recovered at least two independent clones have been obtained which show nonchromosomic inheritance character and an approximately 30-fold increase in methionyl-tRNA synthetase activity as compared to the wild type. Measurement of the Km for methionine in the transformed yeast cells indicates that the activity has been restored by decreasing the Km for methionine to the same level as found for the wild type methionyl-tRNA synthetase. Southern blotting experiments show that the yeast DNA's fragments inserted in the two independent plasmids share a common sequence which must correspond at least partly to the structural gene for methionyl-tRNA synthetase. They also suggest that the methionyl-tRNA synthetase gene is differently orientated in the two plasmids PMID- 6257715 TI - Characterization of 2',3'-O-(2,4,6-trinitrocyclohexadienylidine)adenosine 5' triphosphate as a fluorescent probe of the ATP site of sodium and potassium transport adenosine triphosphatase. Determination of nucleotide binding stoichiometry and ion-induced changes in affinity for ATP. AB - The fluorescent ATP derivative 2',3'-O-(2,4,6-trinitrocyclohexadienylidine) adenosine 5'-triphosphate (TNP-ATP) binds specifically with enhanced fluorescence to the ATP site of purified eel electroplax sodium-potassium adenosine triphosphatase, (Na,K)-ATPase. A single homogeneous high affinity TNP-ATP binding site with a KD of 0.04 to 0.09 microM at 3 degrees C and 0.2 to 0.7 microM at 21 degrees-25 degrees C was observed in the absence of ligands when binding was measured by fluorescence titration or with [3H]TNP-ATP. ATP and other nucleotides competed with TNP-ATP for binding with KD values similar to those previously determined for binding to the ATP site. Binding stoichiometries determined from Scatchard plot intercepts gave one TNP-ATP site/175,000 g of protein (range: 1.64 X 10(5) to 1.92 X 10(5) when (Na,K)-ATPase protein was determined by quantitative amino acid analysis. The ratio of [3H]ouabain sites to TNP-ATP sites was 0.91. These results are inconsistent with "half-of-sites" binding and suggest that there is one ATP and one ouabain site/alpha beta protomer. (Na,K)-ATPase maintained a high affinity for TNP-ATP regardless of the ligands present. K+ increased the KD for TNP-ATP about 5-fold and Na+ reversed the effect of K+. The effects of Na+, K+, and mg2+ on ATP binding at 3 degrees C were studied fluorimetrically by displacement of TNP-ATP by ATP. The results are consistent with competition between ATP and TNP-ATP for binding at a single site regardless of the metallic ions present. The derived KD values for ATP were : no ligands, 1 microM; 20 mM NaCl, 3-4 microM; 20 mM KCl, 15-19 microM; 20 mM Kcl + 4 mM MgCl2, 70-120 microM. These results suggests that a single ATP site exhibits a high or low affinity for ATP depending on the ligands present, so that high and low affinity ATP sites observed kinetically are interconvertible and do not co-exist independently. We propose that during turnover the affinity for ATP changes more than 100-fold owing to the conformational changes associated with ion binding, translocation, and release. PMID- 6257716 TI - Inhibition of sodium and potassium adenosine triphosphatase by 2',3'-O-(2,4,6 trinitrocyclohexadienylidene) adenine nucleotides. Implications for the structure and mechanism of the Na:K pump. AB - Trinitrophenyl derivatives of adenine nucleotides (TNP-nucleotides: 2',3'-O-2,4,6 trinitrocyclohexadienylidene complexes at neutral or basic pH) are potent inhibitors of (Na,K)-ATPase activity. The inhibitory potency of the derivatives tested followed the sequence: TNP-ADP greater than TNP-ATP greater than TNP-AMP much greater than TNP-IMP greater than TNP-adenosine. In the presence of Na+ plus K+, high and low affinity activation of ATPase activity by ATP was observed. Under these conditions, TNP-ATP inhibited (Na,K)-ATPase activity competitively with respect to ATP at the kinetically defined "low affinity ATP site." In the presence of Na+ alone, only high affinity activation by ATP was observed. Under these conditions, TNP-ATP inhibited (Na)-ATPase and enzyme phosphorylation by competing with ATP at the kinetically defined "high affinity ATP site." The Ki values for inhibition were similar to the KD values determined by direct TNP-ATP binding measurements, indicating that the same TNP-ATP site is involved in the inhibition of (Na,K)-ATPase and (Na)-ATPase activities. We conclude that high and low affinity ATP "sites" are interconvertible (i.e. they represent two forms of the same site) and do not co-exist independently. TNP-ATP also inhibited competitively the K+-stimulated p-nitrophenyl phosphatase activity and enzyme phosphorylation by Pi, suggesting that the catalytic site for these substrates is associated with the TNP-ATP site. A kinetic model for (Na,K)-ATPase turnover based on a single ATP site which changes affinity during turnover is presented. The model was analyzed by the King-Altman (1956) J. Phys. Chem. 60, 1375-1378) method to obtain the steady state equation for the rate of ATP hydrolysis as a function of ATP concentration. Computer simulations using published values of the rate constants of intermediate steps suggest that the model is adequate to describe the observed dependence of enzyme activity on ATP concentration and the inhibition by TNP-ATP. The implications of these results on the structure and mechanism of the (Na,K) pump are discussed. PMID- 6257717 TI - High affinity binding of tetanus toxin to mammalian brain membranes. PMID- 6257718 TI - Purification and properties of acetyl-CoA carboxylase phosphatase. AB - Acetyl-CoA carboxylase phosphatase has been purified from the rat epididymal fat pad. The phosphatase occurs in a complex with the carboxylase. In the purification of the phosphatase, the high molecular weight complex was initially separated by sucrose gradient centrifugation, and the phosphatase was isolated from the complex by adjusting to 80% saturation with ethanol and by chromatography on Sephadex G-75. The molecular weight of the phosphatase is 71,000 as determined by sodium dodecyl sulfate gel electrophoresis and gel chromatography on Sephacryl-200 in the presence of 6 M urea. The Km for acetyl CoA carboxylase and glycogen phosphorylase a are 1.5 microM and 37 microM, respectively. The phosphatase has a broad substrate specificity, being active toward glycogen synthase, 3-hydroxy-3-methylglutaryl-CoA reductase, phosphorylase a, phosphoprotamine, and p-nitrophenyl phosphate, in addition to acetyl-CoA carboxylase from fat tissue and liver. Acetyl-CoA carboxylase inhibits the dephosphorylation of phosphoprotamine, indicating that the same activity is responsible for dephosphorylating both substrates. The phosphatase requires no metal ion for activity and is not inhibited by the rat liver phosphorylase phosphatase inhibitor protein. The significance of these findings is discussed in relation to the regulation of acetyl-CoA carboxylase, and the phosphatase is compared to other phosphoprotein phosphatases. PMID- 6257719 TI - Characterization of the structure and reactions of free radicals from serotonin and related indoles. AB - The ESR spectra of the free radicals formed by the autoxidation of serotonin, 5 hydroxyindole, and 5-hydroxytryptophan in 1 N NaOH are presented. The analysis of the hyperfine splitting constants in H2O and D2O characterize these free radicals as semiquinone-imines, the one-electron oxidation product of the corresponding indole. At alkaline pH, autoxidation of these compounds ultimately leads to solid precipitate and unresolved ESR spectra characteristic of polymeric material. The reduction of cytochrome c at pH 7.4 by a wide variety of indoles correlates with the amplitude of the ESR signal in 1 N NaOH, as do other processes thought to be related to 5-hydroxyindole free radical formation. Relative to the rate of cytochrome c reduction, neither serotonin nor the serotonin free radical appears to react with oxygen to form superoxide. In the presence of NAD(P)H, the serotonin radical most probably oxidizes NAD(P)H to form the NAD(P). radical. The NAD(P). radical then reacts with oxygen to form superoxide, which ultimately reduces cytochrome c. PMID- 6257720 TI - The reaction between reduced azurin and oxidized cytochrome c peroxidase from Pseudomonas aeruginosa. AB - The reaction between ferric Pseudomonas cytochrome c peroxidase and reduced azurin was investigated by static titration, rapid scan, and stopped flow techniques as well as circular dichroism measurements. Kinetics of the reduction of the enzyme under pseudo-first order conditions reveals a biphasic logarithmic curve indicating that the reaction between enzyme and azurin is complex and comprises of two reactions, one rapid and a slower one. The relative portion of the fast phase from the overall reaction increases with increasing azurin concentration. Kinetic results can be explained by postulating the presence of two different enzyme forms which are slowly interconvertible. Both enzymatic forms form a complex with reduced azurin. The electron transfer between proteins occurs within the molecular complex of azurin and the peroxidase. PMID- 6257721 TI - Isolation and biochemical characterization of ten-nanometer filaments from cultured ovarian granulosa cells. AB - Ten-nm filaments have been isolated from control and colchicine-treated primary cultures of rat ovarian granulosa cells. Negative stain electron microscopy indicates an average filament diameter of 10.3 nm in the isolated fiber bundles, which, upon sodium dodecyl sulfate polyacrylamide gel electrophoresis, are found to contain a major polypeptide with a molecular weight of 57,000 and several minor components including actin. One-dimensional peptide mapping and two dimensional gel electrophoresis demonstrate similarity between the granulosa cell and baby hamster kidney cell 10-nm filament subunit protein, both of which are distinguishable from keratin, desmin, actin, and tubulin. Quantitative gel densitometry experiments demonstrate little difference in the total amount of the 10-nm filament protein in control cells or cells treated with colchicine, accounting for 12 or 15% of the total cellular protein, respectively. The purification procedure, which involves extraction in Triton X-100 and KCl followed by DNase I treatment, yields 709% of the total granulosa cell intermediate filament protein, and 70% of the newly synthesized 57,000 molecular weight component. Two-dimensional gel electrophoresis of cultures labeled with [32P]phosphate show by autoradiography that the 57,000-dalton polypeptide, actin, and a 130,000-dalton protein are the most readily phosphorylated polypeptides in granulosa cell cultures. These studies identify the major intermediate filament subunit protein of granulosa cells as a 57,000-dalton phosphorylatable polypeptide which comprises a substantial portion of the granulosa cell cytoskeleton. PMID- 6257722 TI - Purification of the gene 0.3 protein of bacteriophage T7, an inhibitor of the DNA restriction system of Escherichia coli. AB - The gene 0.3 protein of bacteriophage T7 prevents the DNA restriction system of EScherichia coli from interfering with T7 infection. A mutant strain of T7 that greatly overproduces the 0.3 protein has been constructed and used for purification of this protein. The 0.3 protein ws found to be extremely acidic and can be separated from virtually all other proteins of the infected cell by chromatography on DEAE-cellulose. Residual contaminating proteins and nucleic acids can be removed by gel filtration, but an even simpler final purification is possible, because under appropriate conditions the 0.3 protein is soluble in high concentrations of ethanol. Thus, a simple, essentially two-step purification can produce about 50 mg of pure 0.3 protein from 30 liters of culture. The purified protein appears to be a dimer of identical subunits. AS expected from its known function during infection, the purified 0.3 protein inhibits the nuclease and ATPase activities of partially purified Eco B, the DNA restriction enzyme of E. coli B, but it does not interfere with several different type II endonucleases tested. The inhibition of Eco B appears to require stoichiometric rather than catalytic amounts of 0.3 protein. PMID- 6257723 TI - Can prenatal X-irradiation in mice act as an initiator stimulus in a modified 2 stage Berenblum/Mottram experiment with postnatal promotion with phorbol ester TPA? AB - Long-term animal experiments with prenatally X-irradiated offspring have so far not unequivocally settled the question of elevated tumor susceptibility. We have pursued this problem further in a modified 2-stage carcinogenesis Berenblum/Mottram experiment. Prenatal X-irradiation of mice has thus been regarded as a possible initiator stimulus, with a postnatal promotion stimulus being given by applying the phorbol ester TPA to the offsprings' skin. This treatment has, however, not produced a higher tumor yield, neither of the skin nor of the internal organs, than that produced by X-irradiation in utero alone. This failure seems partly due to the dysplastic nature of the epidermis of prenatally X-irradiated mice, which also fails to respond to TPA application by way of hyperplasia or by an increased inflammation tendency and ulcer formation. We suggest that a decrease in prostaglandin synthesis after prenatal X irradiation is an important factor for the unchanged tumor susceptibility, especially of the skin. PMID- 6257724 TI - Is upper lip cancer "true" lip cancer? AB - A description is given of the occurrence of upper and lower lip cancers in Finland in the period 1953-1974 with the aim of reaching conclusions on the possible differences in the etiological factors involved. Substantial differences with respect to various epidemiological parameters, such as incidence rates, trends in the incidence with time, male/female ratios of the incidence rates, age incidence curves, urban/rural ratios of the incidence rates, and geographical distribution, were demonstrated between upper and lower lip cancers. On the other hand, similarities in the occurrence of upp]er lip cancer and non-melanomatous skin cancer of the head and neck could be observed. It was concluded that in terms of etiology upper lip cancer could be regarded as a separate entity and different from "true" lip cancer of the lower lip. The role of recurrent herpetic infections of the lips is also discussed. PMID- 6257725 TI - Characterization of the turning response of dorsal root neurites toward nerve growth factor. AB - This study reports that chick dorsal root ganglion neurites undergo a rapid (20 min) reorientation of their direction of growth in response to nerve growth factor (NGF) concentration gradients in vitro. Dorsal root ganglia from chick embryos were explanted onto a collagen-poly-L-lysine substrate. After 24-48 h in culture, NGF gradients were applied to individual growth cones via a micropipette containing 50 biological units NGF/ml. The growth cones turned and grew toward these NGF sources. This turning response was not caused by the trophic effects of NGF on neurite initiation, survival, or growth rate. Dorsal root neurites also grew toward sources of mono- and dibutyryl cyclic adenosine monophosphate (dB cAMP), cyclic guanosine monophosphate (cGMP), and elevated calcium in the presence of the calcium ionophore A23187. These results are consistent with the hypothesis that intracellular levels of cAMP and /or cGMP and calcium may play a role in the turning response of dorsal root neurites toward NGF, but do not establish a causal relationship between the mechanisms of action of NGF, cyclic nucleotides and calcium. Total growth cone adherence to the substrate was measured using a timed microjet of perfusion medium. NGF increased the adherence of growth cones to the substrate, but caffeine and dB cAMP which also elicit the positive turning response, decreased growth cone adherence. Calcium, which did not elicit the positive turning response, produced a greater growth cone adherence to the substrate than that observed with NGF. Although these results do not rule out a role of adhesion changes in axonal turning to NGF, they show that a general increase in adherence does not correlate well with the rapid turning response observed in this study. PMID- 6257726 TI - Binding of thrombin to cultured human fibroblasts: evidence for receptor modulation. AB - Previous work from this laboratory has indicated that thrombin's influence on cell growth can be negative as well as positive. Addition of enzyme to actively growing or confluent cultures of human skin fibroblasts produced growth stimulation, whereas cultures receiving thrombin at the time of subculture displayed inhibited DNA synthesis and mitosis. The specific binding of [125I]thrombin to cells under stimulatory and inhibitory conditions has been studied. Fibroblasts receiving enzyme at subculture bound about two times more [125I]thrombin than those processed in the same way several hours later. The apparent dissociation constant for both groups was approximately 1.5 x 10(-8) M. In each case binding was saturable, although cells receiving enzyme at subculture showed a much higher rate of binding. Experiments were conducted in which enzyme was added to cells at various times after subculture. It was found that the ability of these fibroblasts to specifically bind [125I]thrombin decreased progressively over a 2-h period after subculture and then remained constant for at least 24 h. Evidence is also presented indicating that the binding of [125I]thrombin in both experimental groups was inversely dependent upon the culture density. The biological effects of elevated thrombin binding in cells receiving enzyme at subculture were examined. It was found that inhibited DNA synthesis and altered cellular morphology were directly to this parameter. This study suggests that fibroblasts may possess cryptic thrombin receptors that become exposed during subculture or after injury in vivo. These possibilities and the relationship of cell shape to the availability of thrombin receptors are discussed. PMID- 6257727 TI - Separation of renal medullary cells: isolation of cells from the thick ascending limb of Henle's loop. AB - A homogeneous population of single cells from the thick ascending limb of Henle's loop (TALH) has been isolated from the rabbit kidney medulla. A total medullary cell suspension was prepared by a series of collagenase, hyaluronidase, and trypsin digestions and separated on a Ficoll gradient (2.6-30.7% wt/wt). Morphologically, the cells isolated from the TALH were homogeneous and showed polarity within their plasma membrane structure, with a few blunt microvilli on their apical surface and deep infoldings of the basal-lateral membrane. Biochemically, the TALH cells were highly enriched in calcitonin-sensitive adenylate cyclase and Na, K-ATPase. Alkaline phosphatase and arginine vasopressin sensitive adenylate cyclase, highly concentrated in proximal tubule and collecting duct, were present only in low concentrations in the TALH cells. Additionally, furosemide, a diuretic inhibiting sodium chloride transport in the TALH in vivo, inhibited oxygen consumption of the TALH cells in a dose-dependent manner. The TALH cells were viable, as judged by morphological appearance, trypan blue exclusion, the response of oxygen consumption to 2,4-dinitrophenol, succinate and ouabain, and the cellular Na, K and ATP levels. PMID- 6257728 TI - Purification of calmodulin from Chlamydomonas: calmodulin occurs in cell bodies and flagella. AB - Calmodulin has been purified from cell bodies of the green alga Chlamydomonas by Ca++-dependent affinity chromatography on fluphenazine-Sepharose 4B. Calmodulin from this primitive organism closely resembles that from bovine brain in a number of properties, including (a) binding to fluphenazine in a Ca++-dependent, reversible manner, (b) functioning as a heat-stable, Ca++-dependent activator of cyclic nucleotide phosphodiesterase, and (c) electrophoretic mobility in SDS polyacrylamide gels in both the presence and absence of Ca++, which causes a shift in the relative mobility of calmodulin. Calmodulin has also been identified by the criteria of phosphodiesterase activation and electrophoretic mobility in both the detergent soluble "membrane plus matrix" and the axoneme fractions of Chlamydomonas flagella. Calmodulin is not associated with the partially purified 12S or 18S dynein ATPases of Chlamydomonas. The presence of calmodulin in the flagellum suggests that it is involved in one or more of the Ca++-dependent activities of this organelle. PMID- 6257730 TI - Regulation of development in Dictyostelium discoideum. IV. Effects of ions on the rate of differentiation and cellular response to cyclic AMP. AB - The effects of ionic environment on both the intrinsic rate of differentiation and the response to exogenous cyclic AMP in Dictyostelium discoideum have been examined. K+ specifically inhibits the rate of early development when present at concentrations > 15 mM. Na+ does not inhibit at concentrations up to 25 mM, and can partially overcome K+ inhibition. The maximum rate of development also depends upon the presence of adequate levels of extracellular Ca++. The effect of exogenous cyclic AMP on the rate of development is inhibited by the absence of Ca++, and/or the presence of high concentrations of K+. Under optimal ionic conditions, the only effect of exogenous cyclic AMP on early developments of K+. Under optimal ionic conditions, the only effect of exogenous cyclic AMP on early development is a specific inhibition. The implications of these results for current models of early developmental regulation are discussed. PMID- 6257729 TI - Monensin and FCCP inhibit the intracellular transport of alphavirus membrane glycoproteins. AB - Temperature-sensitive mutants of semliki forest virus (SFV) and sindbis virus (SIN) were used to study the intracellular transport of virus membrane glycoproteins in infected chicken embryo fibroblasts. When antisera against purified glycoproteins and (125)I- labeled protein A from staphylococcus aureus were used only small amounts of virus glycoproteins were detected at the surface of SFV ts-1 and SIN Ts-10 infected cells incubated at the restrictive temperature (39 degrees C). When the mutant-infected cells were shifted to the permissive temperature (28 degrees C), in the presence of cycloheximide, increasing amounts of virus glycoproteins appeared at the cell surface from 20 to 80 min after the shift. Both monensin (10muM) and carbonylcyanide-p- trifluoromethoxyphenylhydrazone (FCCP; 10-20 muM) inhibited the appearance of virus membrane glycoproteins at the cell surface. Vinblastine sulfate (10 mug/ml) inhibited the transport by approximately 50 percent, whereas cytochalasin B (1 mug/ml) had only a marginal effect. Intracellular distribution of virus glycoproteins in the mutant-infected cells was visualized in double-fluorescence studies using lectins as markers for endoplasmic reticulum and Golgi apparatus. At 39 degrees C, the virus membrane glycoproteins were located at the endoplasmic reticulum, whereas after shift to 28 degrees C, a bright juxtanuclear reticular fluorescence was seen in the location of the Golgi apparatus. In the presence of monensin, the virus glycoproteins could migrate to the Golgi apparatus, although transport to the cell surface did not take place. When the shift was carried out in the presence of FCCP, negligible fluorescence was seen in the Golgi apparatus and the glycoproteins apparently remained in the rough endoplasmic reticulum. A rapid inhibition in the accumulation of virus glycoproteins at the cell surface was obtained when FCCP was added during the active transport period, whereas with monensin there was a delay of approximately 10 min. These results suggest a similar intracellular pathway in the maturation of both plasma membrane and secretory glycoproteins. PMID- 6257731 TI - Rat hepatocytes bind to synthetic galactoside surfaces via a patch of asialoglycoprotein receptors. AB - The binding of rat hepatocytes to flat polyacrylamide surfaces containing galactose is sugar-specific, requires Ca+2, and occurs only above a critical concentration of sugar in the substratum [Weigel et al., 1979, J. Biol. Chem., 254, 10,830). Binding is completely inhibited by asialo-orosomucoid but not by orosomucoid or asialo-agalacto-orosomucoid, suggesting that cell binding is mediated by asialoglycoprotein receptors. Asialo-orosomucoid was labeled with fluorescein isothiocyanate and used as a direct fluorescent probe to monitor the distribution of cell surface asialoglycoprotein receptors before and after hepatocyte binding to galactoside or control substrata. Cells bound at 37 degrees C were de-adhered at 4 degrees C using the Ca+2 chelator EGTA. The released cells were then stained with fluorescein-asialo-orosomucoid, fixed, washed, and examined by fluorescence microscopy. On freshly isolated cells before binding, the distribution of asialoglycoprotein receptors appears diffuse and nonclustered. However, more than half of the cells released intact from a galactoside surface had a single large (4 micrometer2) fluorescent patch. The receptor patch cannot be detected on cells while they are bound to a galactoside surface but rather only on released cells, indicating that the cell-substratum junction is the site of the receptor patch. No asialoglycoprotein receptor patches (less than or equal to 1%) were observed on cells that were incubated on, but did not bind to, an underivatized polyacrylamide surface or to a surface with a galactose concentration below the critical concentration for binding. Furthermore, no receptor patches were present on cells that had bound to and were subsequently released from substrata that did not contain galactose, including glass, tissue culture plastic, nontissue culture plastic, and collagen. The distribution of asialoglycoprotein receptors is preserved at 4 degrees C because at 37 degrees C the patches disappear with a half-life of approximately 2.6 min. The results directly demonstrate that a large cluster of asialoglycoprotein receptors mediates the binding of rat hepatocytes to a galactoside surface. PMID- 6257732 TI - Effects of beta adrenergic agents and prostaglandin E1 on erythroid colony (CFU E) growth and cyclic AMP formation in Friend erythroleukemic cells. AB - The formation of erythroid colonies from bone marrow and spleen cells infected with the polycythemic strain of the Friend virus (FV-P) was characterized in an in vitro methyl cellulose colony-forming system in response to prostaglandin E1 and the beta-2 adrenergic agonist, albuterol. Both drugs markedly inhibited the formation of CFU-E colonies of FV-P-infected bone marrow and spleen in the absence or presence of erythropoietin. The albuterol-mediated inhibition of CFU-E colonies (FV-P-infected) was selectively blocked by butoxamine, a beta-2 antagonist. Adenylate cyclase (AC) activity was also determined in FV-P spleen membrane preparations in response to albuterol and PGE1. Both agents stimulated enzyme activity, and butoxamine blocked the stimulation seen with albuterol. The ability of albuterol and PGE1 to stimulate AC activity in the FV-P-infected cells suggests that the effects of these agents on CFU-E formation may be mediated by specific beta-2 adrenergic and PG receptors through the adenylate cyclase-cyclic AMP system. PMID- 6257733 TI - Correlation between growth rate, cell density, and intracellular concentrations of cyclic nucleotides in chemostat cultures of mouse L1210 cells. AB - Constant intracellular concentrations of both adenosine 3',5' cyclic monophosphate (cyclic AMP) and guanosine 3',5' cyclic monophosphate (cyclic GMP) were obtained when mouse leukemia L1210 cells were cultivated under steady-state conditions in the chemostat. When L1210 cells were maintained at a constant growth rate in the chemostat, the mean steady-state intracellular concentration of cyclic AMP decreased with increasing cell density, while the concentration of cyclic GMP remained unchanged. When cell growth rate was increased by three-fold, independently of cell density, in the chemostat, then the mean steady-state intracellular concentration of cyclic GMP increased by 3.6-fold, whereas that of cyclic AMP increased by only 22%. The ratio of cyclic AMP to cyclic GMP was found to decrease with increasing cell growth rate in the chemostat. Our results show that a close correlation exists between the steady-state intracellular concentrations of cyclic nucleotides and changes in both cell growth rate and cell density in chemostat cultures of L1210 tumour cells. PMID- 6257734 TI - Growth of functional primary cultures of kidney epithelial cells in defined medium. AB - Primary cultures of baby mouse kidney epithelial cells can grow without fibroblast overgrowth in a hormone-supplemented serum-free medium (Medium K-1) designed for an established kidney epithelial cell line, MDCK. The five supplements in Medium K-1 are insulin, transferrin, PGE1, T3, and hydrocortisone. Medium K-1 also supports the growth of kidney epithelial cell cultures from a number of animals, including man, without fibroblast overgrowth. Outgrowth of kidney epithelial cells from kidney explants was also observed with Medium K-1. Thus, the medium appears to be selective for epithelial cell growth. The physiological properties of primary cultures of baby mouse kidney epithelial cells were studied in detail. Baby mouse kidney epithelial cells grew at equal rates (0.5 doublings/day) in Medium K-1 and serum-supplemented medium. Medium K-1 also supported the formation of baby mouse kidney epithelial colonies at low cell densities. The dependence of baby mouse kidney epithelial colony formation upon the five factors in Medium K-1 was examined. These studies indicated that the formation of baby mouse kidney epithelial colonies in defined medium depended upon all the five supplements in Medium K-1, in a manner similar, although not identical, to MDCK colonies. Primary cultures of baby mouse kidney epithelial cells grown in Medium K-1 retained kidney cell-associated properties, including the ability to form multicellular domes, a phenomenon associated with transepithelial salt transport. Amiloride-sensitive Na+ uptake and the mucosal surface enzyme leucine aminopeptidase were also observed in baby mouse kidney cultures. Similar functions were observed in MDCK monolayers. PMID- 6257735 TI - Intracellular NAD+ content and ADP-ribose polymerase activity of serum-stimulated baby hamster kidney fibroblasts. AB - We have examined a number of events relating to ADP-ribose metabolism during serum-stimulated growth of BHK-21/C13 fibroblasts. Both the intracellular NAD+ content and the ADP-ribose polymerase activity were found to increase after serum stimulation of cells that were previously arrested by growth in low-serum medium. NAD+ content increased about two-fold, reaching a maximum of 4.2 nmol/microgram of DNA 8 hr after serum steK-21/C13 fibroblasts. Both the intracellular NAD+ content and the ADP-ribose polymerase activity were found to increase after serum stimulation of cells that were previously arrested by growth in low-serum medium. NAD+ content inreased about two-fold, reaching a maximum of 4.2 nmol/microgram of DNA 8 hr after serum step-up. The polymerase exhibited a sharp rise in activity, reaching a peak at about 5 hr after step-up; the activity declined below initial values by 10 hr, and then increased again to reach a plateau at 20 hr. We also report evidence which suggests a possible effect of ADP-ribosylation on the activity of DNA-dependent RNA polymerase I. The activity of this enzyme is diminished in isolated nuclei, and in a subsequent (NH4)2SO4 extract, when the nuclei are incubated with NAD+, the substrate for poly(ADP-ribose) polymerase. This inhibitory effect on the RNA polymerase is abolished when nuclei are incubated also with nicotinamide, a powerful inhibitor of the poly(ADP-ribose) polymerase. PMID- 6257736 TI - The use of lanthanum and cytochalasin B to study calcium effects on skeletal muscle differentiation in vitro. PMID- 6257737 TI - Effect of ouabain on growth regulation by serum components in Balb/c-3T3 cells: inhibition of entry into S phase by decreased protein synthesis. AB - The effect of inhibition of the cell membrane Na+-K+ pump on the Balb/c-3T3 cell growth cycle was studied. Inhibition of the Na+-K+ pump resulted in a dose dependent reduction of intracellular K+ concentration ((K+)i). However, inhibition of protein synthesis in Go/G1 and of subsequent entry into S phase occurred only after (K+)i fell below a critical threshold (50-60 mmoles/liter). Thus, when the (K+)i falls below a critical threshold, protein synthesis is inhibited, preventing cells from entering the S phase. The platelet-derived growth factor (PDGF) induces cells to become "competent" to traverse the cell cycle; the platelet-poor plasma component of serum allows competent cells to progress through G0/G1 and enter S phase. Inhibition of the Na+-K+ pump did not prevent the induction of competence by PDGF, but it did reversibly inhibit plasma mediated events in early G0/G1. Similarly, cycloheximide inhibited plasma mediated events but did not prevent PDGF-induced competence. Thus, protein synthesis may not be required for induction of competence; alternatively, the induction of the competent state may occur in these cells after removal of PDGF and protein synthesis inhibitor. Protein synthesis is required for subsequent plasma-mediated events in G0/G1. PMID- 6257738 TI - Cyclic AMP surges during the dihydrotestosterone-induced growth-division cycle of rat seminal vesicle cells. AB - A single subcutaneous injection of the active androgen DHT (5 alpha-androstan-17 beta-ol-3-one or 5 alpha-dihydrotestosterone; 5 mg/Kg body weight) into rats 7 days after orchidectomy stimulated DNA synthesis in the seminal vesicle, which began between 30 and 35 hr after injection and peaked at 48 hr. Mitotic activity began between 35 and 45 hr after DHT injection and peaked around 55 hr. These proliferative responses appeared to be confined mainly to the epithelial cells of the seminal vesicles. The DHT injection did not rapidly (between 5 min and 2 hr) increase the cyclic AMP level, but it did result in two small later surges of the cyclic nucleotide; the first of which peaked between 18 and 28 hr, but well before the onset of DNA synthesis, and the second of which peaked between 48 and 60 hr, when both the DNA-synthetic and mitotic activities were near or at their peak values. PMID- 6257739 TI - Comparative aspects of oxidative metabolism of neutrophils from human blood and guinea pig peritonea: magnitude of the respiratory burst, dependence upon stimulating agents, and localization of the oxidases. AB - We have compared the subcellular sites of H2O2 and presumably also superoxide-(O2 ) production, and certain aspects of metabolic responses (O2 consumption, O2- production) of stimulated neutrophils from human blood and those elicited into guinea pig peritonea. Stimulation was accomplished with either opsonized zymosan or phorbol-12-myristate-13-acetate (PMA). Striking quantitative differences were observed between these cell types with regard to the increased respiration and O2 production observed during stimulation. These differences were most apparent when opsonized zymosan served as the stimulating agent. They were minimized when the soluble stimulating agent, PMA, was used. With either stimulus, the subcellular sites of H2O2 production were the same for both types of neutrophils, i.e., the plasmalemma and phagosomal membranes. No H2O2 production could be detected cytochemically in the absence of stimulation. Treatment of both unstimulated human blood and elicited guinea pig peritoneal neutrophils with the nonpenetrating, covalently linking reagent, p-diazobenzenesulfonic acid, failed to diminish O2- production upon subsequent stimulation, in contrast to a previous report. These data are discussed in terms of the possible cytological arrangements of the respiratory enzyme(s), and the different modes of stimulation of neutrophil metabolism by various agents. Ancillary data on elicited mouse peritoneal neutrophils are presented. PMID- 6257740 TI - Cell surface localization of 5'AMP nucleotidase in prestalk cells of Dictyostelium discoideum. AB - 5'AMP nucleotidase activity was localized by electron microscopy in Dictyostelium discoideum during cell differentiation. In addition, the activity was assayed by micro enzymic methods in sections dissected from specific cellular regions of lyophilized individuals. The results of the 2 procedures were in agreement, demonstrating that at the culmination stage of development the activity is strikingly localized in the prestalk cells adjacent to the prespore region. The cytochemically stained reaction product appeared only along the plasma membrane of the cells. As prestalk cells migrate into the stalk sheath and undergo differentiation, the activity is rapidly lost. Examination of stained cells at high magnification revealed the product accumulation to be primarily at the cell surface, suggesting that the enzyme functions extracellularly. Occasionally, cells having the morphological appearance of prestalk cells were found within the prespore region. These cells demonstrated 5'AMP nucleotidase activity at their plasma membrane in sharp contrast with neighbouring prespore cells. The strategic localization of 5'AMP nucleotidase may reflect a mechanism for establishing and maintaining regulatory levels of extracellular 5'AMP and/or adenosine during pattern formation in this model system. PMID- 6257741 TI - The role of negative charge in spontaneous aggregation of transformed and untransformed cell lines. AB - No correlation between net negative surface charge as determined by electrophoretic light-scattering techniques and the rates of spontaneous aggregation of 3T3MIT and SVPy 3T3MIT cells has been found. Neuraminidase treatment of both 3T3MIT cells and SVPy 3T3MIT cells causes a significant decrease in electrophoretic mobility but only the 3T3MIT cells show an increase in spontaneous aggregation. An increase in spontaneous aggregation of 3T3MIT cells is seen after growth in 200 mM urea for 18 h but no change in net surface charge occurs. The distribution of anionic sites on the membranes of cells was determined using the ultrastructural marker polycationized ferritin. The distribution of polycationized ferritin-binding sites was essentially identical for both cell lines under all conditions when they were labelled at 4 degrees C. When the cells were labelled with polycationized ferritin at 37 degrees C it was found that cells which have a high net rate of spontaneous aggregation also show rearrangement of anionic sites on their surface membrane. Clustering and rearrangement of anionic sites at 37 degrees C correlate with high rates of spontaneous aggregation. PMID- 6257742 TI - Disordered immune function in patients with polyglandular failure. AB - A standard assessment of immunity was accomplished in 15 patients with the polyglandular failure syndrome and compared to similar studies in appropriate healthy controls. The patients exhibited decreased delayed cutaneous responsiveness and increased serum levels of immunoglobulins G and A. Complement fixing antibody titers to a number of common viruses were equivalent to those observed in controls, but titers ot Coxsackie B4 and B5 viruses were decreased in patients. The decreased antibody titers to Coxsackie B4 and B5 represent an alteration in host protection which is of possible importance in the etiology of polyglandular failure. PMID- 6257743 TI - Luteinizing hormone receptors in human ovarian follicles and corpora lutea during menstrual cycle and pregnancy. PMID- 6257744 TI - The major immunoreactive alpha-melanocyte-stimulating hormone (alpha MSH)-like substance found in human fetal pituitary tissue is not alpha MSH but may be desacetyl alpha MSH (adrenocorticotropin1-13NH2). AB - Pituitary glands were obtained from human abortuses during the second half of gestation. Acid extracts were made from the anterior and neurointermediate lobes, and alpha MSH immunoreactivity (alpha MSHi) was quantified by RIA. alpha MSHi was found in both lobes of the pituitary gland, with 20-80% of the total pituitary alpha MSHi being present in extracts of the anterior lobe. Anterior and neurointermediate lobe extracts subjected to gel filtration on Sephadex G-50 revealed one peak of alpha MSHi having an elution profile identical to those of alpha MSH and desacetyl alpha MSH (ACTH1-13NH2). To characterize further the alpha MSHi extracts were subjected to high pressure liquid chromatography. No alpha MSH could be identified in extracts of the anterior lobe, and most of the alpha MSHi had an elution profile identical to that of desacetyl alpha MSH. Although small amounts of alpha MSH might be present in the neurointermediate lobe, most of the alpha MSHi in this lobe coeluted with desacetyl alpha MSH. Since alpha MSH was not converted to desacetyl alpha MSH during the extraction and chromatographic procedures, we hypothesize that the predominant form of alpha MSH-like material in the human fetal pituitary gland may be desacetyl alpha MSH. PMID- 6257745 TI - Secretion pattern of pro-opiomelanocortin-derived peptides by a pituitary adenoma from a patient with Cushing's disease. AB - Fragments of the pituitary adenoma of a patient with Cushing's disease were maintained in defined culture medium. Immunoreactive (IR) ACTH, IR alpha-MSH, IR beta-lipotropin (beta-LPH), IR beta-endorphin, and IR gamma-MSHs secreted from the adenoma were studied with gel permeation chromatography and the respective RIAs. The adenoma secreted roughly equimolar quantities of IR beta-LPH plus IR beta-endorphin, IR gamma 3-MSHs, and IR ACTHs. It also secreted IR alpha-MSH as well as IR gamma 1-MSH, although in a much lower concentration than the above four peptides. The secreted gamma 3-MSH-like peptides were found to be glycosylated. The secretion pattern suggests that this particular adenoma processes the pro-opiomelanocortin molecule in pathways which encompass those of both the pars distalis and the pars intermedia. PMID- 6257746 TI - Studies on the possible mechanism for deficiency of nonsuppressible insulin-like activity in thalassemia major. AB - Previous studies have shown that serum levels of the somatomedin, nonsuppressible insulin-like activity (NSILA-S), are extremely low in patients with thalassemia major. Since these patients are not GH deficient, several other possible mechanisms for the reduced levels of NSIL-S have been explored. No evidence for the presence of NSILA inhibitors was obtained either in mixing experiments of normal serum and thalassemic sera or after acid gel chromatography of thalassemic sera. The high iron and ferritin levels of thalassemia had no effects on the NSILA-S bioassay itself or on the binding of GH to its hepatic receptors. GH molecules secreted as a result of exercise-induced GH stimulation tests were shown to be both immunologically and biologically reactive. No circulating GH binding proteins were present in thalassemic sera. Since the liver function in the group of patients included in this study was only slightly abnormal, it is considered unlikely that generalized hepatic damage due to the severe iron overload of thalassemia is a major cause. These results suggest that neither NSILA-S inhibitors, abnormal GH molecules, nor hepatic damage contribute to the failure of these patients to produce NSILA-S and that a specific defect may exist at the hepatic GH receptor or postreceptor level. PMID- 6257747 TI - Autoantibodies to the human thyrotropin receptor are not species specific. AB - To ascertain the clinical usefulness of nonhuman thyroid-dependent TSH radioligand-receptor assays, we have reexamined the species specificity of the human TSH receptor-binding site and the unique TSH binding-inhibiting activity (TBI) found in sera from patients with Graves' disease. The human TSH receptor had a high affinity for nonprimate TSH (0.7 + 0.1 x 10(10) M(-1). However, porcine TSH receptors were of higher affinity and ovine TSH receptors were of lower affinity than the human binding site. A human TSH preparation had a similar potency against bovine TSH standard (NIH-B8) when assessed in both human and porcine radioligand-receptor assays (10 + 1.4 U/mg), suggesting that human TSH receptors showed no evidence of species preference. Although immunoglobulins from normal sera had enhanced nonspecific binding to human rather than porcine or ovine thyroid, the interaction of Graves'-specific immunoglobulin was most dependent on the affinity of the TSH receptor for TSH rather than the species from which the thyroid was derived. Hence, of 10 individual globulin fractions chosen to span the range of TBI obtained with human TSH receptor system, there was complete agreement between human and porcine TBI indices. In contrast, 5 preparations became TBI negative using ovine thyroid. These negative globulin fractions were the lowest 5 titers examined, suggesting that titer was the important factor rather than receptor species. Neither the human TSH receptor binding site nor the TBI activity found in sera from patients with Graves' disease demonstrated true species specificity. Hence, porcine thyroid may be substituted for human tissue in clinically applicable TBI assays. PMID- 6257748 TI - Mineralocorticoid response to low dose adrenocorticotropin infusion. AB - The adrenocorticoid responses to low dose ACTH of plasma aldosterone (aldo), corticosterone (B), 11-deoxycorticosterone (DOC), 18-hydroxycorticosterone (18 OHB), 18-hydroxycorticosterone (18-OH-DOC), and cortisol (F) were compared. Alpha ACTH-)1-24) was infused beginning at 0800 h at increasing rates from 12.5-200 mIU/30 min in supine normal subjects under the following conditions: 1) regular Na (120 meq) diet, 2) low Na (10 meq) diet, 3) dexamethasone preadministration (0.5 mg every 6 h for 48 h), and 4) night study (2000 h; 120 meq Na intake). Plasma 18-OH-DOC and B demonstrated quantitatively the greatest responses to ACTH, while DOC and 18-OHB responses were intermediate. Increments in aldo and F were least after ACTH and were maximum at 50 mIU/30 min ACTH, whereas other corticosteroids demonstrated linear responses up to infusion rates of 200 mIU/30 min. All corticosteroids, however, were similar in their threshold responses to ACTH which were at infusion rates of approximately 7-9 mIU/30 min. Na restriction enhanced aldo and 18-OHB responses to ACTH 2- to 3-fold but did not alter the other corticosteroid responses. Dexamethasone pretreatment augmented aldo, 18 OHB, and F responses but did not change the responsitivity of the other corticosteroids to ACTH. Adrenal corticosteroid responses to ACTH were not significantly different between 0800 and 2000 h in subjects on 120-meq Na intake. Thus, corticosteroids show markedly different responses to physiological doses of ACTH, which may have more importance in their regulation than heretofore proposed. Dexamethasone pretreatment enhances aldo, 18-OHB, and F responses to ACTH but does not affect the responses of other corticosteroids. Contrary to reports in experimental animals, corticosteroid responses to ACTH in man do not differ from day to night. PMID- 6257749 TI - Increased 1,25-dihydroxycholecalciferol as a cause of abnormal calcium metabolism in sarcoidosis. PMID- 6257750 TI - The 21-hydroxylase activity in the glomerulosa and fasciculata of the adrenal cortex in congenital adrenal hyperplasia. AB - In the two clinical syndromes of congenital adrenal hyperplasia due to a 21 hydroxylation defect of adrenal steroidogenesis, the simple virilizing and the salt-wasting forms, the 21-hydroxylase activity was studied considering the zona fasciculata and the zona glomerulosa of the adrenal cortex as two separate glands under different regulation. To test this hypothesis, we stimulated adrenal steroidogenesis by ACTH infusion or dietary sodium restriction in eight patients with congenital adrenal hyperplasia (four patients with the simple virilizing form and four with the salt-wasting form of congenital adrenal hyperplasia) and in six normal children. Both the 17-hydroxy and 17-deoxy pathways of adrenocortical steroid biosynthesis were examined by measuring serum concentrations of 17-hydroxyprogesterone, cortisol, progesterone, deoxycorticosterone, corticosterone, and aldosterone and the excretion of free deoxycorticosterone, 18-hydroxydeoxycorticosterone, corticosterone, 18 hydroxycorticosterone, cortisol, and aldosterone. We considered the steroids 18 hydroxycorticosterone and aldosterone to be primarily of zona glomerulosa origin. These studies indicated that the zona fasciculata of both the salt-wasting and the simple virilizing forms is defective in 21-hydroxylation of 17-hydroxy and 17 deoxy steroids. The zona glomerulosa demonstrated deficient 21-hydroxylation only in the salt-wasting form, whereas in the simple virilizing form, the glomerulosa was spared this defect. PMID- 6257752 TI - beta-Endorphin 61-91 and other beta-endorphin-immunoreactive peptides in human semen. AB - Human semen contains large amounts of authentic beta-endorphin and other beta endorphin immunoreactive peptides. To eliminate the non-specific effects of semen in the beta-endorphin RIA, the beta-endorphin immunoreactive peptides were extracted with octadecylsilane-C18 reverse phase beads. beta-Endorphin immunoreactivity was parallel to the RIA standard curve. Sephadex G-50 gel chromatography showed that 93% of the immunoreactive material coeluted with beta endorphin. Reversed phase high pressure liquid chromatography of semen extract demonstrated several peaks of beta-endorphin immunoreactivity; one of these was coincident with synthetic h-beta-endorphin61-91. PMID- 6257751 TI - Medullary thyroid carcinoma identified by cell-free translation of tumor messenger ribonucleic acid in a patient with a neck mass and the syndrome of ectopic adrenocorticotropin. AB - We report a patient who presented with a lateral neck mass and Cushing's syndrome secondary to the ectopic production of ACTH. The initial diagnosis was a nonchromaffin paraganglioma based on conventional light and electron microscopic studies. However, during this patient's hospital course, we determined that mRNA extracted from the tumor directed the translation of a calcitonin precursor in a cell-free system. This finding led to a consideration of the diagnosis of medullary thyroid carcinoma, which was then confirmed by further endocrine and histological evaluations. This is a report of the identification of a tumor type using techniques of molecular biology. PMID- 6257753 TI - Application of a human osteogenic sarcoma cell culture for detection of human cytomegalovirus antibody by immunofluorescence tests. AB - A human osteogenic sarcoma cell culture is useful in the immunofluorescence serological test for detecting human cytomegalovirus antibody. These sarcoma cells are chronically infected with human cytomegalovirus and provide a constant number of immunofluorescence-positive cells. PMID- 6257754 TI - Evaluation of a finger-stick specimen collection method for seroepidemiology of antibody to hepatitis A virus. AB - A finger-stick swab method of collecting blood specimens was shown to compare favorably with the conventional venipuncture method in serological determinations of antibody to hepatitis A virus by radioimmunoassay. PMID- 6257755 TI - Effects of antibodies, trypsin, and trypsin inhibitors on susceptibility of neonates to rotavirus infection. AB - Levels of antirotaviral secretory immunoglobulin A were measured by enzyme-linked immunosorbent assay in colostrum and milk samples collected daily for the first 5 days postpartum from 49 mothers breast-feeding their infants. The trypsin inhibitory capacity of these lacteal secretion samples was assessed by their ability to inhibit the hydrolysis of alpha-N-benzoyl-DL-arginine-p-nitroanilide by trypsin. Stools passed by these breast-fed infants and by an additional 43 bottle-fed infants were pooled by individual and examined by electron microscopy for rotavirus. Stool trypsin levels were estimated with the gelatin hydrolysis test. Breast-fed infants were significantly less likely to become infected with rotavirus and showed significantly lower stool tryptic activity than did bottle fed infants. Breast-fed infants who did not excrete rotavirus over the 5-day period received milk of significantly higher antirotaviral secretory immunoglobulin A or trypsin-inhibitory capacity or both than breast-fed infants who were infected with rotavirus. A case of probable maternal rotavirus infection during pregnancy, producing greatly elevated lacteal antirotaviral secretory immunoglobulin A levels lasting for 2 years, was detected. Results of this study suggest that both antibodies and trypsin inhibitors in human milk can be associated with the protection of neonates against rotavirus infection in the first 5 days of life. PMID- 6257756 TI - Correlation of herpes simplex virus antibody titers and specific lymphocyte stimulation in adult blood donors. AB - Antibody titers to herpes simplex virus type 1 in sera from healthy adult donors were assayed by complement fixation, microneutralization, and an enzyme immunoassay (ELISA). This last test proved to be the most sensitive method for antibody detection. It was estimated that ELISA antibody titers were up to 40 fold higher than neutralizing antibody titers and up to 100-fold higher than complement fixation antibody titers. Due to the higher sensitivity of ELISA, only 3 of 36 blood donors tested in this assay were shown to be seronegative, whereas 6 additional persons of the same group were termed seronegative by the microneutralization assay. Furthermore, four of the latter also did not respond in the complement fixation test. In vitro stimulation of peripheral lymphocytes by using a partially purified herpes simplex virus type 1 particle antigen was achieved for all seropositive blood donors. Only those three donors who were ELISA negative reacted negatively in this stimulation assay. From these results it may be concluded that ELISA is an appropriate method not only for rapid and sensitive antibody determination but also for selecting herpes simplex virus negative patients. PMID- 6257757 TI - Microplate enzyme-linked immunosorbent assay for bovine leukemia virus antibody. AB - A microplate enzyme-linked immunosorbent assay method was developed for the measurement of bovine immunoglobulin G antibody specific to the envelope antigen (glycoprotein 60) of bovine leukemia virus. The test was then performed on 440 serum samples from dairy cows belonging to herds in which bovine leukemia was suspected or which were leukemia free, and the results were compared with those obtained with the gel-diffusion technique. PMID- 6257758 TI - Sensitive chemiluminescent enzyme-linked immunosorbent assay for quantification of human immunoglobulin G and detection of herpes simplex virus. AB - A chemiluminescent enzyme-linked immunosorbent assay (CELISA) was developed for detecting human immunoglobulin G and herpes simplex viral antigen. A comparison of CELISA with a conventional absorptiometric detection system showed that CELISA was 100 times more sensitive than absorptiometry for the measurement of human immunglobulin G. Similarly, CELISA detected as few as 40 plaque-forming units of herpes simplex virus in contrast to 2,500 plaque-forming units detected by absorptiometry. Of 18 specimens which were positive for herpes simplex virus type 1 by isolation in tissue culture, 15 (83%) were detected by CELISA within a few hours; in certain cases, several days were necessary for detection of virus by isolation techniques. PMID- 6257759 TI - Cellular mechanisms of impaired adrenergic responsiveness in neonatal dogs. AB - The myocardial responsiveness of conscious, instrumental dogs to exogenously administered isoproterenol and norepinephrine was investigated in neonatal, 6-wk old, and adult animals. Comparable base-line values for peak left ventricular derivative of pressure with respect to time were observed in all age categories. However, when compared with adult responses, the sympathomimetic amine-induced increases in neonatal left ventricular dP/dt were significantly blunted at each concentration of adrenergic agonist examined, whereas the 6-wk-old puppies displayed an intermediate inotropic response. To investigate the cellular mechanisms of this blunted neonatal response, we correlated physiologic and biochemical measurements of the myocardial responses to catecholamines in each age category. When compared with adult myocardial membrane preparations, neonatal cardiac membranes were characterized in vitro by an increased density of beta adrenergic binding sites, comparable affinity for adrenergic agonists and antagonists, and an enhanced coupling of adenylate cyclase activation to receptor occupancy. Simultaneous changes in either the serum catecholamine concentration or the membrane content of other intrinsic proteins failed to account for the observed neonatal increase in beta-adrenergic receptor density. These findings are most consistent with a compensatory mechanism of the cardiac cell membrane, whereby an inherent depression in the adrenergic responsiveness of the immature myocardium appears to induce the increase in receptor density and activation of adenylate cyclase. PMID- 6257760 TI - Glycoprotein degradation in the blind loop syndrome: identification of glycosidases in jejunal contents. AB - Contents obtained from jejunum of normal controls, self-emptying and self-filling blind loop rats were analyzed for the presence of glycoprotein-degrading glycosidases. The blind loop syndrome was documented by the increased fat excretion and slower growth rate of self-filling blind loop rats 6 wk after surgery. With p-nitrophenylglycosides as substrate, the specific activity of alpha-N-acetylgalactosaminidase, a potential blood group A destroying glycosidase, was 0.90+/-0.40 mU/mg of protein. This level was 23-fold higher than the specific activity of normal controls. In partially purified self-filling blind loop contents, the activity of alpha-N-acetylgalactosaminidase was 9- to 70 fold higher than activities of self-emptying and normal controls. Antibiotic treatment with chloromycetin and polymyxin decreased 24-fold the glycosidase levels in self-filling blind loops. In experiments with natural substrate, the blood group A titer of a20,000g supernate from normal jejunal homogenates decreased 128-fold after 24-h incubation with blind loop contents. Normal contents failed to diminish the blood group reactivity of the natural substrate. Furthermore, blind loop contents markedly decreased the blood group A titer of isolated brush borders. Incubation between blind loop bacteria and mucosal homogenates or isolated brush borders labeled with d-[U-(14)C]glucosamine revealed increased production of labeled ether extractable organic acids. Likewise, intraperitoneal injection of d-[U-(14)C]glucosamine into self-filling blind loop rats resulted in incorporation of the label into luminal short chain fatty acids. These results suggest that glycosidases may provide a mechanism by which blind loop bacteria obtain sugars from intestinal glycoproteins. The released sugars are used and converted by bacteria into energy and organic acids. This use of the host's glycoproteins would allow blind loop bacteria to grow and survive within the lumen independent of exogenous sources. PMID- 6257761 TI - Regulation of secretion in Clara cells: studies using the isolated perfused rat lung. AB - Previous studies from our laboratory indicated that both beta-adrenergic and cholinergic agents stimulate in vivo secretion by rat bronchiolar Clara cells. Those studies also provided support for an in-series beta-adrenergic-cholinergic stimulation of secretion. To further explore the regulation of secretion in Clara cells, and to do it in the absence of systemic influences, we have used the isolated ventilated perfused rat lung. We have again used morphometry and electron microscopy to assess secretion by measuring the volume density (fraction of cell volume) of the secretory granules of bronchiolar Clara cells. We found that in the isolated perfused lung, as in the intact animal, isoproterenol stimulated secretion in Clara cells and that this effect was blocked by the beta adrenergic antagonist propranolol. Pilocarpine, unlike its action in the intact animal, did not stimulate secretion in the isolated lung; rather it inhibited the secretory effect of isoproterenol. Increased tidal-volume ventilation stimulated secretion; propranolol did not block this effect. Analogs of cyclic (c)AMP and of cGMP also stimulated secretion by Clara cells. These findings indicate that there are at least two mechanisms by which Clara cells can be stimulated to secrete. One seems to be beta-adrenergic-cAMP mediated but the triggering event is unknown. The other is initiated by increased tidal volume and cGMP may be involved in the intracellular mediation of this stimulatory event. Finally, we found evidence of beta-adrenergic (stimulatory) -cholinergic (inhibitory antagonism in the regulation of secretion in Clara cells. PMID- 6257762 TI - Pharmacological characterizations of adrenergic receptors in human adipocytes. AB - Three types of adrenergic receptors, beta, alpha-1, and alpha-2, were identified in human adipocytes, isolated from properitoneal adipose tissue, using both the binding of radioactive ligands and the effects of adrenergic agents on receptor specific biochemical responses. Adrenergic binding studies showed the following results: [(3)H]dihydroalprenolol binding (beta adrenergic) B(max) 280 fmol/mg protein, K(D) 0.38 nM; [(3)H]para-aminoclonidine binding (alpha-2 adrenergic) B(max) 166 fmol/mg protein, K(D) 0.49 nM; [(3)H]WB 4101 binding (alpha-1 adrenergic) B(max) 303 fmol/mg protein, K(D) 0.86 nM. In adipocytes from subcutaneous adipose tissue, [(3)H]dihydroergocryptine binding indicated the presence of alpha-2 but not alpha-1 receptors. Beta and alpha-2 adrenergic receptors appeared to be positively and negatively coupled to adenylate cyclase, respectively. Cells or cell membranes were incubated with epinephrine (10 muM) alone and in combination with the antagonists yohimbine (alpha-2) and prazosin (alpha-1). Epinephrine alone prompted a modest increase in adenylate cyclase activity, cyclic AMP, and glycerol release, an index of lipolysis. Yohimbine (0.1 muM) greatly enhanced these actions whereas prazosin was without effect. The beta agonist, isoproterenol, stimulated glycerol release, whereas the alpha-2 agonist, clonidine, inhibited lipolysis and cyclic AMP accumulation. To assess further alpha-1 receptors, cells were incubated with [(32)P]phosphate and epinephrine (10 muM) alone and in combination with prazosin and yohimbine. Epinephrine alone caused a three- to fourfold increase in (32)P incorporation into phosphatidylinositol. Prazosin (0.1 muM) blocked this action whereas yohimbine (0.1 muM) was without effect. Thus, in a homogeneous cell preparation, the human adipocyte appears to have three different adrenergic receptors, each of which is coupled to a distinct biochemical response. PMID- 6257763 TI - Individual variation in the effects of dietary cholesterol on plasma lipoproteins and cellular cholesterol homeostasis in man. Studies of low density lipoprotein receptor activity and 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in blood mononuclear cells. AB - The effects of dietary cholesterol on plasma lipoproteins and cholesterol homeostasis in blood mononuclear cells have been examined in healthy adults. Addition of 1,500 mg of cholesterol to the daily diet of 37 subjects for 14 d was associated with a wide range of response of plasma total cholesterol concentration (from -6 to +75 mg/dl; mean change, +29 mg/dl; P < 0.001). Increases in plasma cholesterol reflected increased cholesterol concentrations in intermediate density lipoprotein (IDL; 1.006-1.019 g/ml), low density lipoprotein (LDL; 1.019-1.063 g/ml), and the HDL(2) subclass (1.063-1.125 g/ml) of high density lipoprotein, which on average accounted for 20, 58, and 22%, respectively, of the total increment. Similar responses occurred in 14 other subjects given 750 mg cholesterol per day for 28 d. Plasma apolipoprotein B concentrations in IDL and LDL also increased. THESE EFFECTS ON PLASMA LIPOPROTEINS WERE ACCOMPANIED BY THREE CHANGES IN FRESHLY ISOLATED BLOOD MONONUCLEAR CELLS: (a) an increase in cell cholesterol content (mean change, +17%; P < 0.01); (b) suppression of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase activity (-32%; P < 0.001); and (c) reduction of LDL receptor activity (-74%; P < 0.01), quantified as the rate of degradation of (125)I-LDL to noniodide trichloroacetic acid-soluble material. These results provide the first direct evidence for the modulation of LDL receptor activity and HMG CoA reductase activity in a peripheral cell type in response to a dietary perturbation of human lipoprotein metabolism.The percentage increase in LDL cholesterol was negatively correlated with the percentage decrease in HMG CoA reductase activity (r = -0.49, P < 0.01). An additional negative correlation existed between the increment in plasma cholesterol concentration and the capacity of cells to degrade (125)I-LDL after derepression by preincubation for 72 h in lipoprotein-deficient medium (r = -0.74, P < 0.001). Thus, differences between individuals in the responses of the plasma lipoproteins to dietary cholesterol appear to be related in part to differences in the capacity of peripheral cells to catabolize LDL and to down regulate cholesterol synthesis. PMID- 6257765 TI - The emergence, localization, and maturation of neurotransmitter systems during development of the retina in Xenopus laevis: II. Glycine. AB - The high-affinity uptake and release of glycine was studied in retinas of Xenopus laevis. In the toad and tadpole retina, 3H-glycine was accumulated by a population of cells located predominantly in the inner nuclear layer. When retinas preloaded with 3H-glycine were subjected to high K+-concentrations, these retinas released large amounts of 3H-glycine by a Ca++-dependent mechanism. The appearance and maturation of these putative glycinergic properties was followed during retinal development. Our results indicate that the high-affinity uptake of glycine first appears around stage 33/34 whereas K+-stimulated glycine release cannot be detected until stage 42. PMID- 6257767 TI - Malignant acanthosis nigricans: a review. AB - Malignant acanthosis nigricans is a dermatosis that appears grossly as a hyperpigmented, velvety, or verrucous hyperplasia of the epidermis, most marked in flexural areas. It is always associated with a malignancy. In 277 cases reviewed, the condition was associated with gastric carcinomas in 55.5%, with other intra-abdominal carcinomas in 17.7%, and with malignancies in other sites in 26.8%. Current theories for the association and pathogenesis of the cutaneous process are discussed. PMID- 6257766 TI - The emergence, localization, and maturation of neurotransmitter systems during development of the retina in Xenopus laevis. III. Dopamine. AB - The uptake, synthesis, and release of dopamine was studied in retinas of Xenopus laevis. In the tadpole and adult retina, 3H-dopamine is accumulated by cells located in the inner nuclear layer. Retinas preloaded with 3H-dopamine release this compound in response to high K+ concentrations in the medium. This release is probably Ca++-dependent as it is inhibited by Co++ in the medium. Adult retinas are also capable of synthesizing 3H-dopamine from 3H-tyrosine. The appearance and maturation of these dopaminergic properties were followed during retinal development. Our data indicate that synthesis of dopamine can first be detected as early as stage 35/36 whereas uptake of dopamine first occurs at stage 43. K+-stimulated release of preloaded 3H-dopamine from putative dopaminergic neurons is, however, not evident until stage 46. These results show that similar to the development of GABA-ergic and glycinergic properties, the uptake, synthesis, and release mechanisms for dopamine emerge at different stages during retinal differentiation in Xenopus Laevis. PMID- 6257764 TI - Regulation of endothelial cell cyclic nucleotide metabolism by prostacyclin. AB - An analysis of prostaglandin-stimulated adenosine 3',5'-cyclic monophosphate (cyclic AMP) accumulation in cultured human umbilical vein endothelial cells showed prostacyclin (PGI2) to be the most potent agonist followed by prostaglandin (PG)H2, which was more potent than PGE2, while PGD2 was essentially inactive. The endothelial cells studied apparently have a high rate of cyclic AMP phosphodiesterase activity because significant PGI2-mediated increases in cyclic AMP could not be shown in the presence of the phosphodiesterase inhibitor isobutylmethylxanthine (MIX). Endoperoxide PGH2-stimulation of cyclic AMP accumulation was inhibited 75--80% by the prostacyclin synthetase inhibitors 12 hydroperoxyeicosatetraenoic acid or 9,11-azoprosta-5,13-dienoic acid. These data indicate that the PGH2-stimulation is due primarily to conversion to PGI2. The beta-adrenergic agonist L-isoproterenol stimulated cyclic AMP accumulation in the endothelial cells. This accumulation was completely blocked by propranolol. However, stimulation of cyclic AMP accumulation by the beta-adrenergic agent did not equal that induced by PGI2. Furthermore, the PGI2 response could not be blocked by propranolol. Thrombin-stimulated PGI2 biosynthesis was attenuated by PGE1 or isoproterenol in the presence of MIX. MIX alone was less effective than a combination of PGE1 or isoproterenol plus MIX. These data suggest two potential effects of PGI2 biosynthesis by endothelial cells: first, the PGI2 can elevate cyclic AMP in platelets, and second, endothelial cell cyclic AMP can be elevated as well, so that subsequent PGI2 synthesis will be attenuated. PMID- 6257768 TI - A glomus tumor mimicking a peripheral neuropathy. AB - A patient was found to have a solitary glomus tumor near the posterior cutaneous branch of the ulnar nerve at a wrist. For years, his symptoms mimicked a peripheral neuropathy. The location, color, and soft vascular consistency of the lesion helped us to make the correct diagnosis in this case and simple ablation of the lesion effected a cure. PMID- 6257769 TI - Some effects of nitrogen fertilizer on the chemical composition of pearl millet grain. PMID- 6257770 TI - Protein quality of rice as affected by application of nitrogen fertilizer. PMID- 6257771 TI - Nitrogen fertilization effects on amino acid composition of pecan (Carya illinoensis) nutmeats. PMID- 6257772 TI - Regional odontodysplasia: clinical, pathologic, and therapeutic considerations. AB - A case of regional odontodysplasia in a 9-year-old boy is presented. Clinical and pathologic characteristics of this developmental anomaly and its treatment are reviewed. PMID- 6257773 TI - Peripheral neuropathy in the elderly: a clinical and electrophysiologic study. AB - Fifty-nine elderly patients with clinical and neurophysiologic evidence of peripheral neuropathy were reviewed. Diabetes, alcoholism and malignancy were the important etiologic factors, but other causes of acquired neuropathy such as drugs, autoimmune disease, and acute or chronic demyelinating neuropathy continue to warrant attention. Postural hypotension associated with neuropathy occurred in three patients with diabetes and one patient with lymphoma. Prognosis for the neuropathies did not seem to be adversely affected by age. PMID- 6257774 TI - [Epstein-Barr virus infections in pregnancy. The serological profile of active infections in pregnant women. Their possible relationship with perinatal mortality (author's transl)]. AB - A significant number of cases of deaths and of perinatal misfortunes are still of unknown origin. The role of pathological infection is probably important in these cases and particularly those in the Torch group of viruses, and among these, as has been shown by epidemiological and virological tests, the Epstein-Barr virus (E.B.V.). The authors have undertaken a prospective study based on serology, looking for E.B.V. antibodies in pregnancy. 1,164 women were studied and 74 of these had perinatal abnormalities. There is a significant relationship between active E.B.V. infection and mishaps in pregnancy. PMID- 6257775 TI - [Trophoblastic pseudotumour of the uterus (author's transl)]. AB - When perforation of the uterus occurred while a therapeutic termination of pregnancy was being carried out in a 25-year-old woman it was shown that the monomorphic trophoblastic pseudotumour was invading the myometrium. It was not secreting HCG when it was diagnosed and it had not recurred 19 months after the diagnosis and hysterectomy. PMID- 6257776 TI - [Condylomas, cervical dysplasias and carcinoma of the cervix (author's transl)]. AB - Because the greater number of viral cervical lesions, the authors recall their cytological and pathological pictures. In 30% of the causes, they have observed relations between flat condylomas and cervical severe dysplasias and carcinoma in situ. But in these last lesions, the cytological characters of the viral infestations are not visuable. The relationship between condyloma and carcinoma in situ is explained by the virus modifications on the germinative cells genoma which enhance great multiplication of these cells and inhibit the epidermoid differentiation. When the virus are not very active, or the host responses sufficient, the cell differentiation and maturation permit the replication of the virus and its appearance in the cytoplasm of the superficial cells. The authors stress on the complete destruction of the viral cervical lesions and the later control of the cervix. PMID- 6257777 TI - Hepatitis A virus infections in Voyvodina. AB - Sera of 1000 persons in Voyvodina were tested with radioimmunoassay for antibodies against hepatitis A virus (HAV). The morbidity and age incidence of positive findings have been analysed and compared with relevant findings in other countries. Below the age of 19 years the morbidity rates are higher (0.138 to 0.595 per mill) and the prevalences of seropositives are lower (17.1-64.0%) than the respective frequencies above that age (0.011 to 0.052 per mill and 85.7-98.7% respectively). Below the first year of life seropositivity is more frequent than in 1- to 14-year old children. After the first year until the age of 30-39 years the frequency of seropositives increases with increasing age up to a maximum of about 90%. PMID- 6257778 TI - Diagnosis of recent hepatitis A infection: a comparison of two methods for detecting specific IgM. AB - Radioimmunoassay (RIA) tests for anti-hepatitis A virus (HAV) IgM were carried out on 728 sera: 283 were tested by both a method using an anti-mu serum bound to a solid phase and a method involving preliminary separation of igM by sucrose density gradient (SDG) centrifugation, 354 by the anti-mu method alone and two by the SDG method alone. Similar proportions of sera were found to be positive by each method (42.5%, 41.7%), but equivocal results were commoner by the SDG method (4.7% compared with 1.5%). There were 21 (5.5%) discrepant results from the sera tested by both methods, 20 of which could have been due to the higher sensitivity of the anti-mu method. The SDG method generally gave unequivocal results on sera collected within six weeks of the onset of jaundice. Separation of the IgM fraction by re-orientation centrifugation was quick, but otherwise offered no special advantage over separation on a swing-out rotor. The use of 2 mercaptoethanol (2 ME) reduction to assess the purity of the IgM fraction increased confidence in the specificity of the test. It led, however, to the exclusion of 16 reactive sera (4.2%), all of which were found to be positive in the anti-mu test. The anti-mu method gave better discrimination between positive and negative sera than the SDG method and detected IgM both earlier and later in infection. The results of tests designed to check the specificity of the anti-mu procedure were satisfactory. As it is potentially cheaper and easier to perform, the anti-mu method seems, in all respects, to be superior to the SDG method. PMID- 6257779 TI - Detection and quantification of IgM, IgA, IgG1 and IgG2 antibodies against foot and-mouth disease virus from bovine sera using an enzyme-linked immunosorbent assay. AB - A simple solid-phase enzyme immunoassay is described for the detection of antibody classes showing activity against foot-and-mouth disease (FMD) virus in bovine sera. The assay achieves a preliminary separation of the specific class of antibody from other serum proteins through immuno-adsorption to class-specific immunoglobulin-coated wells of micro-titre plates. The specific antibody is reacted with FMD virus, which is then detected by an enzyme-labelled anti virus IgG. PMID- 6257780 TI - Adenovirus eye infections in an Australian city, 1972-9. AB - A number of adenovirus serotypes have been associated with both sporadic cases and outbreaks of conjunctivitis and pharyngoconjunctival fever but only adenovirus type 8 and adenovirus type 19 have been responsible for wide-spread epidemic kerato-conjunctivitis. In Melbourne, Australia, in the past eight years these two serotypes have been prevalent, resulting in an outbreak of adenovirus type 8 kerato-conjunctivitis in 1976-7 followed by adenovirus type 19 kerato conjunctivitis in 1978-9. During these two periods of peak incidence, 53 cases of adenovirus type 8 and 43 cases of adenovirus type 19 kerato-conjunctivitis were confirmed by isolation. PMID- 6257781 TI - Epidemiological and serological study of hepatitis A virus outbreaks in France: a comparison between immunoadherence and radioimmunoassay. AB - An epidemiological study and the simultaneous evaluation of anti-HAV antibody using radio immunoassay (RIA) and immunoadherence hemagglutination assay (IAHA) was performed during three hepatitis A epidemics in the Tours area (France). Fifty-seven sera from 35 subjects with viral hepatitis type A and 16 sera from nine children who did not develop any clinical signs of hepatitis were studied. The more explosive epidemic occurred in an institution for mentally retarded children (attack rate 68%). The two major outbreaks observed were due to the introduction of the institutions of individuals infected with hepatitis A virus. Two out of three of the index cases had a seafood dinner three to four weeks before onset of jaundice. Sera taken one week after jaundice were always found to be anti-HAV positive by both RIA and IAHA, and sera taken more than three days before the appearance of jaundice were negative by both methods. Sera taken at the peak of the transaminase elevation were anti-HAV positive by RIA but only one out of two were positive by IAHA. The anti-HAV titre by RIA increased from the time of the appearance of jaundice and the highest titres, over 1/20000 were seen only after several months. Observations of subjects in close contact with patients who seroconverted without any manifestation of hepatitis, confirmed the existence of clinically mute infections. PMID- 6257782 TI - The prevalence of serum neutralizing antibodies to infectious bovine rhinotracheitis virus in Scotland. AB - The prevalence of serum neutralizing antibodies to infectious bovine rhinotracheitis virus in 1152 serum samples from adult cattle in 114 dairy and beef herds in different regions of Scotland was 12%. In the Grampian region, the number of seropositive cattle in the self-contained herds was significantly less (P less than 0.01) than in the "other" herds. Holstein cattle had been introduced into five of these "other" herds, and significantly more (P less than 0.01) of the samples from these five herds were seropositive compared with the samples from the rest of the "other" herds in the same region into which recently purchased cattle had been introduced. The introduction of Holstein cattle was also a major factor in the association between the prevalence of antibodies and herd size in the Grampian region. The prevalence of serum neutralizing antibodies to infectious bovine rhinotracheitis virus was significantly greater (P less than 0.001) in this survey than in those previously undertaken in the United Kingdom. PMID- 6257783 TI - Viruses in sewage as an indicator of their presence in the community. AB - The results of a three year study of the viruses isolated from sewage by means of five tissue culture types are reported. The enteroviruses identified demonstrated a seasonal pattern which was similar to that of clinical isolates. Echoviruses and coxsackieviruses displayed a changing pattern of dominant serotypes in both sewage and clinical isolates; echovirus 6, 19, 3 and coxsackievirus B4, B5, A9 successively became the most common serotypes. The poliovirus in sewage was all vaccine-like in character. Reovirus, type 2 was abundant; adenovirus, of several serotypes, were the least often identified. PMID- 6257784 TI - Spontaneous cytotoxicity against virus-infected cells: relationship to NK against uninfected cell lines and to ADCC. AB - Cellular immunoadsorption and cold cell competition assays were used to examine the specificity of NK. Lymphocytes nonadherent to monolayers of cells persistently infected with Sendai virus (SV-HEp2) were almost totally depleted of NK against the uninfected tumor cell lines K562, MOLT-4, and HSB, as well as against SV-HEp2, when assayed immediately after separation. Lymphocytes adherent to SV-HEp2 monolayers were also partially depleted of NK against these targets. After overnight incubation, the nonadherent cells remained relatively depleted of NK against all targets, compared to controls. The adherent cells displayed a variable amount of activity, depending on the donor; in all cases, however, substantial NK activity was observed in this fraction against all targets, infected and uninfected. Exogenous interferon failed to augment the activity of the nonadherent lymphocyte fraction. Cellular immunoadsorption on monolayers of K562 or HSB was similarly found to partially deplete NK against SV-HEp2, as well as against the homologous cells. Cold cell inhibition studies showed that SV-HEp2 and, to a lesser extent, HEp2, could inhibit the lysis of K562; similarly, K562 could partially inhibit the lysis of SV-HEp2. We concluded that infected and uninfected target cells are lysed by overlapping populations of NK effector cells. In addition, the ADCC activity of SV-HEp2-adherent and nonadherent lymphocyte fractions was examined immediately after separation. Whereas the nonadherent lymphocytes were depleted of both ADCC and NK, the adherent lymphocytes were partially depleted of NK yet contained high levels of ADCC activity. PMID- 6257785 TI - Accessory cells in the in vitro generation of type C viruses specific T killer lymphocytes. I. Role of macrophages in primary anti-FMR reaction. AB - The role of macrophages has been studied in in vitro cytolytic T lymphocytes- (CTL) mediated responses directed against the FMR cell-surface antigens induced by C type viruses. Macrophages, defined as Thy 1.2-negative, Ia-positive, adherent, phagocytic, radioresistant cells present in the spleen and the peritoneal cavity, are required to obtain primary in vitro anti-FMR responses. In most of our experiments they were not necessary in secondary reactions. In primary responses, macrophages and responder T cells must be compatible at least at the I region of the major histocompatibility complex. Anti-Ia antibodies inhibit the response. A rat soluble factor (Interleukin 2) can replace macrophages in primary anti-FMR CTL-mediated reactions. These results suggest that macrophages function during primary anti-FMR response by interacting with a helper T cell rather than with CTL precursors. In agreement with this hypothesis, it appears that the H-2 restriction of F1 hybrid anti-FMR CTL generated in vitro in primary reaction is not related to the H-2 specificities of the parental macrophages used and depends only on the H-2 antigens of the stimulating tumor cells. PMID- 6257786 TI - Relative lack of Epstein Barr virus (EBV) receptors on B cells from persistently EBV seronegative adults. AB - Viral receptors are essential for the entry of the virus into the cell. EBV receptors can be detected on fresh lymphocytes by a technique that uses EBV coupled tanned red blood cells that form rosettes with lymphocyte-bearing receptors. This technique was found to detect viral receptors only and not surface immunoglobulins. T cell depletion of the lymphocyte population showed that these receptors were present on B lymphocytes. Study of the presence of these EBV receptors on the surface of fresh lymphocytes from 66 subjects (age 2 to 66), selected out of a group of over 2000 individuals, showed that the majority of these donors had receptors for the virus. However, a few of these adults persistently failed to develop anti-EBV antibodies, even if they were in close contact with the infectious agent. The lymphocytes of 11 such individuals were found to be lacking EBV receptors. Transformation assay of these lymphocytes did not give rise to lymphoblastoid cell lines whereas lymphocytes from 4 individuals, who were EBV seropositive or seronegative but receptor positive, yielded permanent lymphoblastoid cell lines. This would suggest that a few EBV seronegative adults (less than 0.5%) display natural resistance to EBV transformation of their lymphoid cells as a result of absolute or relative lack of EBV receptors on these cells. PMID- 6257787 TI - Age-associated changes in Epstein-Barr virus-induced human lymphocyte autoantibody responses. AB - In the present investigation we have studied the capacity of the Epstein-Barr virus (EBV), a ubiquitous human B lymphocyte polyclonal activator, to induce cultured peripheral blood lymphocytes from umbilical cords, young adults (20 to 40 yr old), and elderly adults (75 to 90 yr old) to form IgM antibodies to human IgG or human thyroglobulin. The EBV preparation used was shown to exert its B cell stimulatory effect independently of T cell-suppressor effects. The cultures were studied in limiting dilution analyses, and the data were taken to represent relative numbers of B cell precursors of autoantibody-forming cells in the 3 age groups. The results showed: 1) the EBV-inducible IgM anti-IgG and anti thyroglobulin-producing cells increased in number from birth to old age; 2) the rise occurred at different times of life for the 2 autoantibodies, anti-IgG reactive B cells increasing between birth and young adulthood, and anti thyroglobulin reactive B cells between young adulthood and old age; 3) the apparent relative avidity of the anti-IgG for antigen was higher in the elderly adults than in the younger adults. We believe these findings are determined by differences in the frequencies of the respective self-reactive B cells in the circulation. What physiologic or environmental factors determine the differential expansions of the human autoreactive B lymphocytes for IgG and thyroglobulin are not known. It seems possible that individual variations in the sizes of these pools may be a factor in determining susceptibility to autoimmune disease. PMID- 6257788 TI - Genetic influences on the augmentation of natural killer (NK) cells during murine cytomegalovirus infection: correlation with patterns of resistance. AB - Cytotoxic activity attributable to natural killer (NK) cells was augmented in the spleens of mice infected with murine cytomegalovirus (MCMV). Stimulation was observed as early as 10 hr after virus administration but was dependent upon the dose used, and in particular, the host genotype. Effector cells were capable of killing a range of tumor cell targets as well as normal syngeneic thymocytes, and were induced in nude (nu/nu) and heterozygous (nu/+) mice. A significant correlation existed between resistance to the lethal effects of MCMV infection and the degree of NK cell augmentation by this virus in 10 of 11 strains examined. Non-H-2 related differences in activity were observed, but a clear association between high NK cell responses and the possession of a particular H-2 haplotype was not apparent. Beige mutant C57BL/6J mice, previously reported as defective in NK cell function were susceptible to MCMV and expressed low levels of cytotoxicity during infection. Thus, the genetically controlled stimulation of NK cells in the early stages of infection with MCMV may contribute to the genotype related patterns of resistance seen with this virus. PMID- 6257790 TI - Epidermal cyclic GMP is increased in psoriasis lesions. AB - Cyclic GMP levels in epidermis of normal subjects and of psoriatic patients were measured with a highly sensitive radioimmunoassay method. Technical improvements for the assay are 2-fold: (1) skin samples were frozen in vivo before biopsy and local injection of any anesthetic was avoided to overcome ischemia effect which could lower cyclic GMP artificially; (2) epidermis was microdissected to avoid contamination of dermis and keratin layers. The results show that on a per mg tissue dry weight basis the cyclic GMP levels are about 200 fmol in the involved lesional epidermis and 70 fmol in the uninvolved or normal epidermis. Similarly increases in the cyclic GMP levels in the lesional epidermis are observed when the data are expressed either on a DNA or protein basis. The cyclic GMP level in normal epidermis from nonpsoriatic subjects is the same as that in the uninvolved epidermis of psoriasis patients. PMID- 6257789 TI - Enzymes of purine nucleotide metabolism in human lymphocytes. AB - A methodology is presented for systemic analysis of purine enzymes in small lymphocyte subfractions. For the determination of 7 different enzymes of purine metabolism *hypoxanthine-guanine phosphoribosyltransferase (HG-PRT), adenine phosphoribosyltransferase (A-PRT), adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), adenosine kinase (AK), 5'-nucleotidase (5'N), and AMP deaminase) less than 200,000 peripheral blood lymphocytes are needed. 1000-6000 lyophilised lymphocytes are incubated in micro-incubation vessels (3 microliter) with radioactive substrates for 15-180 min. Separation of substrates and products is achieved by thin-layer chromatography on PEI-cellulose. Addition of BSA to the incubation mixtures results in higher specific enzyme activities and narrower ranges of mean values of a control group. PMID- 6257791 TI - Normal and psoriatic keratinocytes and fibroblasts compared in culture. AB - The ability of psoriatic fibroblasts to stimulate growth of epidermal cells was studied by comparing the capacity of murine 3T3 cells, normal fibroblasts and psoriatic fibroblasts to act as feeder layers for cultured normal human keratinocytes. 3T3 cells consistently gave shorter times to confluency than normal or psoriatic cells which were about the same. The SDS polyacrylamide gel electrophoretic pattern of the fibrous protein was identical irrespective of the feeder layer use. Psoriatic epidermal cells could be grown from single cell suspensions by using 10(-9) M cholera toxin in the medium. The cultured psoriatic keratinocytes grew identically to normal cells and made the same fibrous protein. The psoriatic keratinocytes also grew better on 3T3 cells than normal or psoriatic fibroblasts. PMID- 6257792 TI - Identification of papillomaviruses in butchers' warts. AB - We have studied the papillomaviruses found in the hand warts of 60 butchers, most of them from 2 distant slaughterhouses. Warts differing in morphology and location were studied separately. The viruses were identified by molecular hybridization, restriction enzyme analysis and immunofluorescence. Four known human papillomaviruses (HPV-1, HPV-2, HPV-3, HPV-4) were detected and one hitherto unknown papillomavirus was identified in 9 butchers. The DNA of the latter virus did not anneal with any of the RNAs complementary to either HPV-1 to HPV-5 or bovine papillomavirus type 1 (BPV-1) DNAs, and showed a Hind II + III restriction enzyme cleavage pattern distinct from those of known HPVs and BPVs. This virus showed distinct antigenic properties, as shown by immunofluorescence, using HPV-1, -2, -3, -5, and BPV-1 antisera. It may represent a new type of human papillomavirus (HPV-7) or a yet unidentified animal papillomavirus. In addition, 6 butchers were found to be infected with a papillomavirus, distinct from the known skin HPVs and from BPV-1, which could not be characterized by restriction enzyme analysis. Eleven butchers were found to be infected by 2 viruses. A characteristic histological pattern was found to be associated with the different papillomaviruses. PMID- 6257793 TI - Congenital cytomegalovirus infection in an urban Canadian community. AB - congenital cytomegalovirus (CMV) infection was diagnosed in 64 (0.42%) of 15,212 infants born in Hamilton, Ontario, Canada, during a period of 44 consecutive months. Urine specimens collected within 48 hr of birth were screened for CMV by inoculation into cell cultures. Only four infants had clinical or laboratory findings in the first week of life that suggested cytomegalic inclusion disease; CMV infection was mild or inapparent in the remainder. Fourteen CMV-positive infants (21.9%) had birth weights of less than or equal to 2,500 g, including eight of 11 premature infants (less than or equal to 37 weeks of gestation). Only five CMV-positive infants were small for gestational age. Overall, there were no significant differences between CMV-positive and CMV-negative infants in mean gestational age or mean measurements of weight and head circumference at birth. Mothers of CMV-positive infants were predominantly younger, primiparous women of lower educational and economic status, and the number who were unmarried was about threefold greater than among mothers of uninfected infants. PMID- 6257794 TI - Patterns of shedding of hepatitis A virus antigen in feces and of antibody responses in patients with naturally acquired type A hepatitis. AB - Serial stools and sera from 13 patients with hepatitis A were collected during an epidemic in 1978 in a rural village near Hangzhou, China, and were studied to determine the patterns of shedding of hepatitis A antigen (HAAg) and of antibody response in some cases. Of 44 stool specimens, 31 were HAAg-positive by a radioimmunoprecipitation-polyethylene glycol assay. The highest percentage of HAAg positivity was in stools collected one week before and one week after the peak elevation of serum glutamic pyruvic transaminase (SGPT) levels, and peak HAAg shedding in each patient usually occurred in the early stools. Fecal shedding of HAAg was detected as early as day 19 before peak elevation in SGPT level and as late as day 11 afterward and continued for at least 25 days. The pattern of HAAg shedding in feces and of complement-fixation and immune adherence antibody response in relation to the change in SGPT activity and jaundice in four patients with hepatitis A was demonstrated. PMID- 6257795 TI - A two-year study of bacterial, viral, and parasitic agents associated with diarrhea in rural Bangladesh. AB - Enteric pathogens associated with diarrhea were studied for two years at a diarrhea treatment center in rural Bangladesh. Enterotoxigenic Escherichia coli (ETEC) was the most frequently identified pathogen for patients of all ages. Rotavirus and ETEC were isolated from approximately 50% and approximately 25%, respectively, of patients less than two years of age. A bacterial or viral pathogen was identified for 70% of these young children and for 56% of all patients with diarrhea. Most ETEC isolates were obtained in the hot dry months of March and April and the hot wet months of August and September. Rotavirus identification peaked in the cool dry months of December and January, but infected patients were found year-round. The low case-fatality rates for patients with watery diarrhea and substantial dehydration further document the usefulness of treating patients with diarrhea with either a glucose- or sucrose-base electrolyte solution such as those used in this treatment center. PMID- 6257796 TI - Pathogenesis of herpes simplex labialis. I. Replication of herpes simplex virus in cultures of epidermal cells from subjects with frequent recurrences. AB - Primary cultures were established with epidermal cells from the skin of 11 patients with frequent episodes of herpes simplex labialis and 13 control subjects with titers of neutralizing antibody to herpes simplex virus (HSV) type 1 but no history of herpetic disease. Confluent monolayers were exposed to HSV type 1 strain E115, and the infection was monitored by assay of the rate of virus appearance in the culture medium. The mean slope of the virus growth curves ([log10 pfu/ml]/log10 hr) was 9.0 in cultures from patients vs. 9.5 in cultures from controls, and the respective mean titers of virus 53 hr after infection were 10(6.8) and 10(6.5) (differences not statistically significant). Genetically controlled host factors may play some role in the clinical response to HSV infection, but variation in the susceptibility of epidermal cells, the natural target for HSV, is not one of the critical determinations. PMID- 6257797 TI - Effect of influenza virus infection on susceptibility to bacteria in mice. AB - A model of combined infection was established with intranasal influenza virus and systemic Listeria monocytogenes infections of mice. Prior infection of mice with influenza virus markedly influenced resistance to subsequent challenge with L. monocytogenes. If mice were infected with influenza virus within the 24-hr period before challenge, a substantial increase in mortality was reflected by enhanced growth of Listeria in the spleen. If mice were infected with influenza virus three or five days before challenge, mortality was decreased, with an accompanying reduction in the growth of Listeria in the spleen. Thus, pulmonary infection with influenza virus has a major effect on susceptibility to systemic infection, exerting a depressive effect on host resistance in the first 48 hr and then causing a longer period of enhanced resistance. PMID- 6257799 TI - Interruption of experimental rhinovirus transmission. AB - Aqueous iodine (2%) applied to the fingers was effective in blocking had transmission of experimental rhinovirus infection. None of eight volunteers became infected when exposed to rhinovirus immediately after treatment of the fingers with iodine. All of seven similarly exposed subjects treated with a placebo preparation became infected (P less than 0.001, Fisher's exact test). One of 10 volunteers became infected when exposed 2 hr after treatment of fingers with iodine, compared with six of 10 who became infected in the control group (P = 0.06, Fisher's exact test). Virus was recovered from three (11%) of 27 hand rinses from volunteers using iodine and from 11 (41%) of 27 hand rinses from volunteers using the placebo preparation (P less than 0.03), Fisher's exact test). PMID- 6257798 TI - Vaccination for the prevention of maternal and fetal infection with guinea pig cytomegalovirus. AB - Live guinea pig cytomegalovirus (CMV) vaccine was prepared after 11 serial passages in tissue culture; noninfectious envelope antigen vaccine was prepared by n-octyl glucoside treatment of CMV-derived dense bodies and virions. Hartley strain guinea pigs immunized with either vaccine were compared with guinea pigs inoculated with virulent, salivary gland-passaged CMV (approximating natural infection), with passively immunized animals, and with nonimmune controls. All vaccinated animals had neutralizing antibodies to CMV. After challenge with virulent CMV, animals previously inoculated with either tissue culture-passaged or virulent CMV were protected against acute viremia and death; pregnant animals previously inoculated with live CMV vaccine had lower incidences of viremia and generalized maternal and fetal infection. Envelope antigen-vaccinated and passively immunized pregnant animals showed acute viremia after similar challenge with virulent virus; however, infection was less generalized than that in control animals, and CMV was not isolated from the fetuses of these vaccinated mothers. PMID- 6257801 TI - Human colostral cytotoxicity. II. Relative defects in colostral leukocyte cytotoxicity and inhibition of peripheral blood leukocyte cytotoxicity by colostrum. AB - Colostral cells have been previously shown to mediate antibody-dependent cellular cytotoxicity (ADCC) to herpes to simplex virus-infected cells. A comparison of colostral cells to matched peripheral blood mononuclear cells has revealed significantly lower ADCC activity, higher antibody requirements, and slower kinetics of colostral cell ADCC against infected cells. Colostral cells failed to mediate natural killer cytotoxicity. Lymphocytes, monocyte macrophages, and polymorphonuclear leukocytes isolated from peripheral blood and incubated with colostrum from virus-immune or nonimmune women markedly inhibited ADCC. Inhibitory activity was found in lipid and aqueous fractions and was due to an effect on leukocytes, not target cells. A partial explanation was inhibition of expression of leukocyte Fc receptors, a prerequisite for ADCC, by acellular colostrum. These results raise questions concerning the potential antiviral activity of colostral cells in vitro. PMID- 6257800 TI - Cytomegalovirus infection and specific cell-mediated immunity after marrow transplant. AB - Patients were studied prospectively after marrow transplant to correlate cytomegalovirus (CMV) infection with the in vitro lymphocyte transformation response to CMV antigen. Ninety-two (58%) of 158 patients developed CMV infection. The lymphocyte response to CMV antigen of patients who were seropositive before transplant was significantly suppressed immediately after transplant. Isolation of CMV was associated with further suppression of responses; seroconversion to CMV was associated with a significant increase. The lymphocyte response of 73 long-term survivors was similar to that of normal persons. The presence of antibody to CMV in the donor before transplant had little effect on the lymphocyte response of patients after transplant even though the patients' lymphocyte s were of donor origin. As in previously reported studies of immunity to other herpesviruses after marrow transplant, it was concluded that recovery of the response to CMV antigen is related primarily to active virus infection and not to patient or donor pretransplant immunity. PMID- 6257802 TI - Passive bacteriocin typing of strains of Clostridium perfringens type A causing food poisoning for epidemiologic studies. AB - A passive bacteriocin typing system was developed for use as an epidemiologic tool to study outbreaks of food poisoning caused by Clostridium perfringens type A. The 90 strains tested were from England, the United States, India, Japan, France, and Canada. Forty of 74 strains produced bacteriocin when irradiated with ultraviolet light for 40-90 sec. Eight bacteriocins were concentrated with ammonium sulfate and titrated on a common indicator strain. These bacteriocins were found to be specific for C. perfringens type A. All of the 90 strains were typable, with 16 distinct bacteriocin types. Most (85.56%) of the strains were types 1-6. Strains of C. perfringens type A clustered into certain patterns of bacteriocin types according to their country of origin and source of isolation. PMID- 6257803 TI - [A case of adenoid-cystic carcinoma of the trachea treated by the circumferentio segmental resection of the trachea (author's transl)]. PMID- 6257804 TI - [Collagenase, dipeptidylpeptidase IV, and cathepsin D activities in gingival fluid and whole saliva from patients with periodontal disease (author's transl)]. PMID- 6257805 TI - [Preparation of hard crown and bridge resin without PMMA powder (III) (author's transl)]. AB - We have been studying hard crown and bridge resins. Mixtures of several polyfunctional monomers and a composite filler finely pulverized, prepared by polymerization of trimethylolpropane trimethacrylate in the presence of hydrophobic colloidal silica, were polymerized and their mechanical properties were studied. They were excellent and a sample from 2.6 E.UDMA comonomer was the best among them. The new filler possessed better affinity with matrices than composite fillers reported previously, presumably due to the reactivity with matrices. Introduction of this new filler into the hard crown and bridge resin preparation must improved the resins remarkably. PMID- 6257806 TI - [A case of selective hypoaldosteronism (author's transl)]. PMID- 6257807 TI - [A case of encephalitis associated with cytomegalovirus infection in a renal transplant recipient (author's transl)]. PMID- 6257808 TI - Coronary artery spasm as a cause of myocardial ischemia. PMID- 6257809 TI - Iron increases collagenase production by rabbit synovial fibroblasts. AB - Ionic iron, as the chelate FeNTA, was taken up by rabbit synovial fibroblasts in monolayer culture. Uptake was accompanied by increased production of latent collagenase and PGE2. Concomitant addition of desferrioxamine, a specific chelator of Fe+++, prevented iron uptake and induction of collagenase and PGE2. Collagenase induced by iron may have a role in the pathogenesis of certain disease states associated with abnormal iron deposition. PMID- 6257810 TI - Dermal analogue tumours of major salivary glands. AB - Monomorphic adenomas of the major salivary glands manifest a histologic spectrum whose diversity rivals that of pleomorphic adenomas. In nearly all forms of monomorphic adenomas there are histologic features which recall stages in the embryonic development of salivary glands and/or adenexae of skin. A close histogenetic relationship between certain monomorphic adenomas and certain adenexal tumours of skin is suggested by the findings of this report. Within the diversity of expression found in monomorphic adenomas are subsets of tumours which are analogous and nearly homologous with dermal appendage tumours, especially the dermal eccrine cylindroma. The analogous relationship is carried further by a proposed diathesis in which patients exhibit histologically similar tumours in their salivary glands and skin. PMID- 6257811 TI - Pleomorphic adenoma of the nasal septum. Report of two cases. PMID- 6257812 TI - Late-recurring calcifying adenoid cystic carcinoma. Report of a case. AB - A recurring adenocystic carcinoma originating in the floor of the maxillary antrum in a 75-year-old man is described. The primary tumour had been surgically removed from the mucous membrane of the hard palate 22 years earlier. Histological examination showed deposits of calcification in the tumour tissue. The authors believe this feature to be a sign of the slow-growing variant of adenocystic carcinoma. PMID- 6257813 TI - Synovial sarcoma of the soft palate in a child: a light and electron microscopic study. AB - An extremely rare case of synovial sarcoma localized in the soft palate of a 9 year-old boy is reported, describing all details noted during light and electron microscopic observation. All features characteristic of this mesenchymal tumour were evident in the light microscopy. Electron microscopy also confirmed the diagnosis. The text includes full particulars of the therapy administered. PMID- 6257814 TI - Pleomorphic salivary gland adenomas of the parapharyngeal space. Review of nine cases. AB - Nine cases of pleomorphic salivary gland adenomas of the parapharyngeal space are reviewed. In the discussion which follows we show that five of these tumours were situated medial to the superior constrictor muscle and arose within pharyngeal mucosa. We also outline our views on the management of pleomorphic salivary gland adenoma of the parapharyngeal space with particular reference to biopsy, surgical excision and post-operative radiotherapy. PMID- 6257815 TI - A double-blind comparative study of trimethoprim-polymyxin B versus trimethoprim sulfacetamide-polymyxin B otic solutions in the treatment of otorrhea. AB - This was a double-blind randomized study to compare the safety and efficacy of trimethoprim-polymyxin B (TP) and trimethoprim-sulfacetamide-polymyxin B (TSP) drops in the treatment of otorrhea. The 68 cases treated suffered from external otitis, recurrent otitis media with tympanic membrane perforation, or infected mastoid cavities and post-operative tympanoplasties. The TP ototopical solution was successful in 60.6 per cent of cases compared to 88.6 per cent of cases with TSP. These rates were statistically different using the Chi Square with Yates' correction method. There were no signs of ototoxicity, fungal infection overgrowth or local sensitivity to either of the solutions. The study has shown that both drugs are equally safe and that TSP is significantly more effective in the treatment of otorrhea. PMID- 6257817 TI - An improved procedure for the synthesis of 14C-labeled phosphatidylserine from cerebral phosphatidic acid. AB - A complete procedure to prepare a highly labeled phosphatidyl-L-[U-14C]serine possessing the same fatty acid composition of brain phospholipids is reported. CDP-diglyceride was synthesized by reaction between phosphatidic acid and CMP morpholidate as the dicyclohexylcarboxamidium salt. The reaction between CDP diglyceride and L-[U-14C]serine to produce the labeled phosphatidylserine was catalyzed by the CDP-diglyceride: L-serine phosphatidyl transferase (EC 2.7.8.8) from E. coli. A selective inhibition of phosphatidylserine decarboxylase activity, present as contaminant in the enzyme extract, was introduced in order to avoid a low yield of product. Traces of phosphatidylethanolamine (about 1%) were easily removed by preparative thin-layer chromatography. The yield of the labeled product was as high as 87% and it specific radioactivity was 170 mCi/mmol. PMID- 6257816 TI - The enzymes of phospholipid synthesis in Clostridium butyricum. AB - We have examined extracts of Clostridium butyricum for several enzymes of phospholipid synthesis. Membrane particles were shown to catalyze the formation of CDP-diglyceride from [3H]CTP and phosphatidic acid. The reaction was dependent on Mg2+ and stimulated by monovalent cations. CDP-diglyceride formed in vitro was found to be a substrate for both phosphatidylglycerophosphate synthetase and phosphatidylserine synthetase. The formation of phosphatidylglycerophosphate from added CDP-diglyceride and [U-14C]sn-glycerol-3-phosphate was dependent on Mg2+ and Triton X-100. The dephosphorylation of endogenously-generated phosphatidylglycerophosphate to yield phosphatidylglycerol was observed to be pH dependent. The formation of phosphatidylserine from CDP-diglyceride and L-[3 14C]serine was stimulated by Mg2+ and Triton X-100. dCDP-diglyceride was a suitable substrate for both phosphatidylglycerophosphate synthetase and phosphatidylserine synthetase. Phosphatidylserine decarboxylase activity was barely detectable in membrane particles from C. butyricum. The addition of E. coli membrane particles provided efficient phosphatidylserine decarboxylase activity in this system. Although plasmalogens are the principal lipids of C. butyricum, none of the products of phospholipid synthesis formed in vitro contained measurable amounts of plasmalogens. The subcellular distribution of both phosphatidylglycerophosphate synthetase and phosphatidylserine synthetase in C. butyricum was also studied. Both were found to be membrane-associated. PMID- 6257818 TI - Effects of treatment with adrenocorticotrophin on the hypothalamo-pituitary adrenal system. AB - Long-term treatment with adrenocorticotrophin (ACTH) inhibited the stress-induced response of the hypophysial-adrenocortical system 24 h after the final ACTH injection. The mechanism of this phenomenon was studied in both normal and adrenalectomized rats, the latter receiving corticosterone at various doses. The effect of electrical stimulation of the medial basal hypothalamus on the concentration of corticosterone in plasma (an indicator of ACTH secretion), the corticotrophin releasing factor (CRF) content of the stalk median eminence (SME), the ACTH content of the pituitary gland and the in-vitro release of ACTH by the pituitary gland incubated with or without addition of SME extract were investigated. Electrical stimulation of the medial basal hypothalamus failed to induce a rise in concentrations of corticosterone in plasma of normal rats treated with ACTH; moreover the levels of hypothalamic CRF and hypophysial ACTH were significantly decreased. Hemipituitary glands of ACTH-treated rats released markedly less ACTH in vitro in response to SME extract than did the control glands. This indicated that long-term hormone administration caused a serious impairment of the responsiveness of the corticotrophic cells toward CRF. Pituitary ACTH content and in-vitro responsiveness of pituitary glands obtained from ACTH-treated, adrenalectomized rats receiving corticosterone replacement seemed to be dependent on the amount of exogenous corticosteroid, but not on that of exogenous ACTH. Our previous and present findings suggest that long-term treatment with ACTH elicits repeatedly increased secretion of endogenous corticosterone, impairing the stress-induced CRF-ACTH release at both the hypothalamic and hypophysial levels. Our data challenge the view that ACTH itself is able to inhibit its own secretion. PMID- 6257819 TI - Culture sensitization and inhibition of luteinizing hormone responsive production of cyclic AMP in luteal cells by luteinizing hormone, prostaglandin F2 alpha and [D-Trp6]-luteinizing hormone releasing hormone. AB - Many cells are able to regulate their sensitivity to hormones. In order to investigate the mechanism(s) by which rat luteal cells regulate their sensitivity to LH, we have developed and characterized a cell culture model. Cultures of dispersed rat luteal cells were exposed to graded doses of bovine LH, an analogue of LH releasing hormone (LH-RH) ([D-Trp6]-LH-RH), and prostaglandin F2 alpha (PGF2 alpha) for 3 h. The media containing these hormones were then replaced with fresh hormone-free medium and the cells cultured for 24 h. In order to test the sensitivity of these cultures after 24 h, the medium was discarded and replaced by medium alone, or medium containing a standard dose of bovine LH for 1 h. The amount of cyclic AMP accumulated during this hour was used as an index of the sensitivity of the cells to LH. Control cultures became 'supersensitive' to LH with augmented production of cyclic AMP during culture but LH-receptor binding activity was not increased. During the first 2 h of culture, LH (100 ng/ml) increased accumulation of cyclic AMP by fourfold, but after 5 h of culture, stimulation of cyclic AMP accumulation by the same dose of LH was increased 32 fold, 299-fold at 13 h and 359-fold at 21 h of culture. The increase in LH responsive accumulation of cyclic AMP with cultured was severely impaired by early exposure of cells to LH, LH-RH analogue or PGF2 alpha during the first 2 h of culture. Also, both LH-RH analogue and PGF2 alpha acutely inhibited LH stimulated accumulation of cyclic AMP. Inhibition of culture-induced sensitization of LH responsiveness was not altered by the addition of 3-isobutyl 1-methylxanthine. Scatchard analysis of LH binding sites indicated that pretreatment of luteal cells with LH (or human chorionic gonadotrophin at an equivalent dose) reduced the number of free LH receptors when measured after 24 h of culture, but total receptor binding activity was not changed. However, a similar effect was not seen with cells treated with PGF2 alpha or LH-RH analogue. It is suggested that 'culture-induced' supersensitivity may represent either recovery of pre-isolation sensitivity or result from the loss of an endogenous factor(s) which retards the coupling of the LH receptor and adenylate cyclase. Although PGF2 alpha and LH-RH analogue have been shown to directly prevent the occupied LH receptor from activation of adenylate cyclase, the present observations have indicated that this inhibitory process was continued even when these agents were removed from the culture medium. PMID- 6257820 TI - Relationship between gill Na+,K+-activated ATPase activity and osmotic stress in the plecopteran nymph, Paragnetina media. AB - A relationship between osmotic stress and gill Na+,K+-activated ATPase was observed in plecopteran nymphs acclimated to diluted creek water and a hypertonic medium. An increase of 84% in diluted creek water is presumably related to an active uptake of sodium ions from the hypotonic medium. Whereas a 21% decrease in the enzyme activity may be related to the morphological changes in the specialized cells in the gills. The Na+,K+-activated ATPase activity was also compared with the Malpighian tubules and the rectum. The highest ATPase activity of 32.6 +/- 2 mumoles Pi mg protein-1 30 min-1 was observed in the Malpighian tubules. The activity in the gills (19 +/- 1.2 mumoles Pi mg-1 30 min-1) was slightly lower than the rectum. Since the ATPase activity in the gills is quite high, the gills can be considered to play an active role in hyperosmotic regulation in plecopteran nymphs. PMID- 6257821 TI - Potentiation of the cGMP-induced guinea pig acrosome reaction by zinc. AB - The addition of 8 bromo cGMP (10 mM) immediately (approximately 2 min) upon suspension of Guinea pig sperm in glucose-free BWW medium induces a significant number of acrosome reactions within minutes. The simultaneous addition of micromolar concentrations of ZnCl2 (25-1000 microM) potentiates the cGMP effects. Mid-micromolar concentrations were able to dramatically increase the percentage of acrosome reactions by a factor of 6.5 over 8 bromo cGMP alone. The induction of acrosome reactions was dependent upon external Ca++, and it is suggested that in this species Zn++ functions by affecting cyclic nucleotide metabolism and/or Ca++ flux. PMID- 6257822 TI - DNA-binding proteins in the nuclei of herpes simplex virus-infected, arginine deprived, BSC-1 cells. PMID- 6257823 TI - Isolation of the glycoprotein of vesicular stomatitis virus and its binding to cell surfaces. AB - The glycoprotein (G) of vesicular stomatitis virus (VSV) was radiolabelled, extracted and purified so that its potential interaction with host cell surfaces could be studied. When BHK-21 cells were incubated with the radiolabelled virus glycoprotein, the virus component rapidly attached to the cell surface. The attachment was shown to be temperature-dependent adn saturated at approx. 3 X 10(5) molecules/cell. The omission of Mg2+ or Ca2+ from the incubation medium had little effect on the glycoprotein binding. Treating the isolated G protein and intact virions with neuraminidase did not significantly decrease their binding to BHK-21 cells. Pre-incubating cells with trypsin did not decrease the attachment of VSV virions nor the binding of purified G protein. Treating cells with phospholipase A or phospholipase C suggested that the binding of the glycoprotein and the intact virion might have been dissimilar. Unlabelled glycoprotein competitively inhibited binding of the labelled molecules although the presence of intact virions did not inhibit attachment of the G protein. Likewise, saturating amounts of the glycoprotein did not decrease binding of VSV to BHK-21 cells. These observations suggested that either the isolated glycoprotein bound to cell surface components that were distinct from the virion receptor or that the manner of the purified glycoprotein attachment differed from the G protein still associated with the intact virion. Chemical crosslinking and diagonal two dimensional gel electrophoresis were used to identify and to compare the cell surface components responsible for glycoprotein and virion attachment. PMID- 6257824 TI - the influence of the host cell on the inhibition of virus protein synthesis in cells double infected with vesicular stomatitis virus and mengovirus. AB - The ability of mengovirus to inhibit the synthesis of vesicular stomatitis virus (VSV) proteins and of VSV to inhibit the synthesis of mengovirus proteins during double infection in three different cell lines was investigated. Although cellular protein synthesis was inhibited after infection of cells by each virus, the ability of one virus to decrease translation of the mRNA species of the co infecting virus varied with the cell type. Superinfection of mengovirus-infected L-929 cells by VSV resulted in essentially no inhibition in the synthesis of either mengovirus or VSV proteins. In HeLa cells and CHO cells the synthesis of both VSV and mengovirus proteins was inhibited under conditions of simultaneous or sequential infection. The inhibition of VSV protein synthesis after infection of HeLa cells by mengovirus was not a result of a modification or inactivation of virus mRNAs. When extracted from double infected cells, the VSV mRNAs manifested normal biological activity, as determined by their ability to stimulate the synthesis of VSV proteins in a micrococcal nuclease-treated cell-free system from L cells. The interference of non-interference of one virus by another in different cell lines was also measured by quantifying the number of infectious particles produced in each cell line. The results were similar to those reported above for protein synthesis inhibition. These experiments suggest that the interference of mengovirus with VSV mRNA translation in HeLa cells is not necessarily reflective of the mechanism by which mengovirus inhibits cellular protein synthesis. Also, the host cell appears to influence the extent or nature of the interference of one virus by the other. PMID- 6257825 TI - Serological and immunological relations between the 146S and 12S particles of foot-and-mouth disease virus. AB - Intact 146S particles of the seven serotypes of foot-and-mouth disease virus (FMDV) produce type-specific precipitating, complement-fixing and neutralizing antibodies in cattle and guinea-pigs. However, the 12S structural subunit, produced from the virus particle by mild acid treatment (pH 6) or by heating at 56 degrees C, although stimulating the production of precipitating and complement fixing antibodies, produces only low levels of neutralizing antibody. Nevertheless, 12S antibody in guinea-pigs primed with a vaccine prepared from 146S particles. Moreover, heterotypic 12S and 146S particles also boosted the neutralizing antibody response to the first virus. These results point to an antigenic similarity between the 146S particles of each type and to a close antigenic relationship between the 146S and 12S particles. PMID- 6257826 TI - A study of the level of nucleotide sequence conservation between the RNAs of two types serotypes of foot-and-mouth disease virus. AB - The level of nucleotide sequence conservation between the RNAs of type A and type O foot-and-mouth disease virus (FMDV) has been compared by three methods. (I) RNA hybridization of fragments containing either the poly(C) tract at the 5' end of the RNA of the poly(A) tract at the 3' end of the RNA indicates that there is a similar level of sequence conservation (65% homology) across the genome. RNase T1 fingerprinting of these fragments did not show the presence of any long regions of completely conserved nucleotides apart from the poly(C) and the poly(A) tracts. (2) RNase T1 fingerprints of the RNA on the 5' side of the the poly(C) tract (the S fragment) show that there is more conservation in this region of the RNA than indicated by the hybridization results. (3) Direct nucleotide sequencing of the poly(C) tract and of the 54 nucleotides at the 5' end of the two genomes shows that there is considerable sequence conservation at the extreme 5' end of the RNA. PMID- 6257827 TI - Antiviral effects of atropine and caffeine. AB - The antiviral activities of atropine and caffeine were investigated. Atropine inhibited the multiplication of enveloped viruses and caffeine suppressed th growth of polio, influenza, herpes simplex and vaccinia viruses but not Japanese encephalitis virus, Newcastle disease virus and type 2 adenovirus. PMID- 6257828 TI - Polypeptides of feline leukaemia virus: identification of p15(E) and p12(E). AB - Antiserum to the p15(E) polypeptide of Rauscher murine leukaemia virus (R-MuLV) precipitated two proteins from purified virions of feline leukaemia virus (FeLV) with apparent mol. wt. of 18500 and 155000 on SDS-polyacrylamide gels. These proteins have been designated p15(E) and p12(E), in line with the nomenclature for MuLV proteins. Like the analogous protein of MuLV, FeLV p15(E) was found to be disulphide-linked to the virion glycoprotein, gp70. FeLV p15(E) was sensitive to digestion of intact virus particles with the proteolytic enzyme, bromelain, indicating that this protein is on the outer surface of the virion. An analysis of cat sera for precipitating activity for FeLV p12(E) showed this only in sera from cats which had recovered from FeLV infection and had virus-neutralizing activity. PMID- 6257829 TI - Review article the biology of the arenaviruses. PMID- 6257830 TI - A study of the cross-reacting antigens on the intact foot-and-mouth disease virus and its 12S Subunits with antisera against the structural proteins. AB - Cross-reactions between two strains of foot-and-mouth disease virus (FMDV) belonging to different serotypes (A and O) were studied with intact virus and virus subunits and antisera produced against the isolated structural proteins. Anti-VP1 type O serum showed cross-reactive neutralizing activity, in contrast to the sera raised against intact virus type O, whereas anti-VP1 type A serum only neutralized homologous virus. Anti-VP2, VP3 and VP4 did not show neutralizing activity. In the enzyme-linked immunosorbent assay and radio-immunoassay anti VP1, -VP2, and -VP3 sera reacted with the 12S virus subunits of both serotypes. No activity was obtained against VP4. Competition experiments with virus subunits of virus type A and O show that anti-VP1 serum is the most type-specific. Anti VP2 serum is completely cross-reactive, while anti-VP3 serum reacted in an intermediate way. The identical reactions obtained with anti-VP2 sera and the homologous and heterologous virus subunits suggest that the exposed VP2 antigens are identical. PMID- 6257831 TI - In situ study of SV40 virus DNA in lytic infection by mild loosening of nucleoproteins. AB - We have studied SV40 (simian virus40) nucleoprotein in permissively infected monkey kidney cell cultures (CV1) by a procedure which does not require the isolation of the SV40 chromosomes. Treatment of the cells by a low ionic strenght medium containing Photo flo produces a mild loosening of nucleoproteins, and permits the in situ study in ultrathin sections of virus components and their relationships with host cell chromatin. RNP and DNP could be distinguished by uranyl-EDTA-lead staining (for RNP) and by DNase digestion. SV40 DNA was observed as circular molecules, either free or connected with either RNP fibrils or virus capsids. These three aspects were interpreted, respectively, as viral minichromosomes, transcription of virus genome and partially encapsidated virus DNA. During encapsidation a few virus particles appear to be bound to host chromatin. Many, if not all, seemingly mature viruses, singly or in small linear clusters, are also aligned on host chromatin. Some of these observations were corroborated by the Miller spreading technique. They are consistent with a role for the host cell chromatin in the production of nuclear viruses. PMID- 6257833 TI - Tubular structures in mixed infection with herpes simplex virus type 1 and type 2. PMID- 6257832 TI - Varicella-zoster virus transformation of hamster embryo cells. AB - Varicella-zoster virus infection of primary hamster embryo cells resulted in oncogenic transformation. These transformed cells exhibited virus-specific antigens by immunofluorescence and developed surface Fc receptors. They induced aggressive fibrosarcomas when injected into inbred hamsters. The tumour-bearing hamsters develop antibodies to varicella-zoster antigens. PMID- 6257834 TI - Virus RNA species in kirsten murine sarcoma virus-transformed mink cells. AB - The nuclear and cytoplasmic RNAs from Kirsten murine sarcoma virus (KiMuSV) transformed non-producer mink cells were studied for the species of virus specific RNA by fractionation in agarose gels, transfer to diazotized aminophenylthioether paper and hybridization to complementary DNA probe. In both nuclei and cytoplasm, only genome-length KiMuSV-specific RNA was detected. No subgenomic virus RNA species was detected in poly(A+) or poly(A-) RNA fractions. The same observations were made in KiMuSV-transformed mink cells superinfected with feline leukaemia viruses. The significance of these findings is discussed. PMID- 6257835 TI - HSV-1 infection inhibits procollagen and protein secretion from normal and ataxia telangiectasia cultured skin fibroblasts. AB - Human skin fibroblasts derived from a healthy individual and from a child with the genetic disorder ataxia telangiectasia were infected with herpes simplex virus type 1 (HSV-1). The virus infection did not affect the synthesis of procollagen but inhibited its release from the cells. PMID- 6257836 TI - Properties of adeno-associated virus (type 1) replicated in rodent cells by murine adenovirus. AB - We report for the first time the replication of infectious adeno-associated virus type 1 (AAV-1) in rodent cells [primary mouse kidney (PMK) and mouse L929 cells] using murine adenovirus (MAV) as a helper virus and also the production of AAV-I virus antigen by herpes simplex virus type I (HSV-I) with its temperature sensitive mutant ts 200 in mouse neuroblastoma (NB) cells. The infectious AAV virions produced by MAV on L cells had a buoyant density of 1.41 2ml in caesium chloride gradients. PMID- 6257837 TI - The structure of herpes simplex virus type 1 DNA as probed by micrococcal nuclease digestion. AB - Micrococcal nuclease digestion was used to probe the structures in which herpes simplex virus type I (HSV-I) DNA is found during virus replication. Parental DNA, progeny DNA and DNA in nucleocapsids were analysed. Parental DNA was examined after infection of Vero cells with 32P- or 3H-thymidine-labelled HSV-I. Progeny DNA was examined after HSV-I-infected Vero cells were pulse-labelled with 3H thymidine during HSV-I DNA synthesis. In both cases, nuclei were isolated and digested with micrococcal nuclease. Digestion products were analysed by agarose or polacrylamide gel electrophoresis (PAGE). Most parental DNA remained as intact molecules. However, a small amount was degraded into fragments which were heterogeneous in size or the size of nucleosomal cell DNA. These two classes of fragments were also produced upon digestion of progeny DNA. The heterogeneous fragments and nucleosomal fragments comprised major and minor fractions, respectively, of digested progeny DNA. When digested DNA from HSV-I-infected cells was transferred from composite polyacrylamide-agarose gels to diazobenzyloxymethyl paper, nucleosomal fragments hybridized to 32P-labelled HSV I DNA as well as to 32P-labelled Vero cell DNA.. Therefore, nucleosomal fragments contained HSV-I DNA sequences. HSV-I DNA in nucleocapsids was analysed by micrococcal nuclease digestion after nucleocapsids were disrupted with PH 9.3 buffer, pyridine, Sarkosyl or NcCl/urea. Only fragments of heterogeneous size were produced. Thus, HSV-I DNA is found predominantly in structures other than nucleosomes during virus replication. PMID- 6257838 TI - Replication of human cytomegalovirus at supra-optimal temperatures is dependent on the virus strain, multiplicity of infection and phase of virus replication. AB - The kinetics of replication of five strains of human cytomegalovirus (CMV) were studied to determine the influence of (i) temperature, (ii) virus strain, (iii) m.o.i. and (iv) cell type. Relative to growth at 37 degrees C (m.o.i. = 3 to 9) eclipse periods were extended from 24 to 48 h at 33 degrees C and to 72 h at 40.5 degrees C. Yields were reduced at 33 degrees C and almost eliminated at 40.5 degrees C. No replication occurred in most instances at 40.5 degrees C and with 0.05 p.f.u./cell. Temperature shift studies (40.5 to 37 degrees C) indicated that the block to replication at 40.5 degrees occurred about 12 to 16 h p.i. resulting in little synthesis of CMV DNA or late antigens. The degree of inhibition of late functions at 40.5 degrees C is virus strain and m.o.i. dependent, but is not dependent on the type of fibroblastic cell used. These data suggest that persistent CMV infections are favoured at 40.5 degrees C. PMID- 6257839 TI - Nuclear magnetic resonance studies of the phenylalanine residues of eukaryotic cytochrome c. AB - The resonances of Phe 82 and Phe 10 in the nuclear magnetic resonance spectra of horse cytochrome c are reassigned using nuclear Overhauser enhancements. The reassignments provide new information about the oxidation state linked conformation change of cytochrome c. The region of the protein now known to be affected by the change extends to the part of the protein close to Phe 10. PMID- 6257840 TI - EPR of Cu+2 binding to apo-yeast enolase. AB - We have studied the electron paramagnetic resonance (epr) spectra of complexes of apo-yeast enolase with 65Cu+2 in the presence and absence of substrate and magnesium ion. An unusual epr spectrum with large g parallel, large g and A rhombicity and very narrow line-widths (10 G) is seen for the first two 65Cu+2 bound in the presence of substrate 2-phosphoglycerate (2PGA). the epr parameters, consistent with rhombic and tetragonal distortion of an octahedral geometry of the coordination sphere of the Cu+2 are g = (2.123, 2.042, 2.405) and A = (2.58, 4.19, 12.0) mK. The high g parallel and absence of super-hyperfine splitting are strong evidence for absence of nitrogen ligands. In the presence of Mg+2 and 2PGA, the Cu+2-enolase solutions exhibit a complex epr spectrum reflecting exchange and dipolar interaction between the first two Cu+2 ions bound. The spectra of Cu+2 plus enolase in the presence and absence of Mg+2 without 2PGA are distinct but not unambiguous, each reflecting at least two inequivalent binding sites. In addition to providing information on the geometry and location of the divalent cation binding sites, the data show unequivocally that imidazole residues, previously found to have a role in catalysis, do not participate in Cu+2 binding. Although Cu+2 does not activate the enzyme, direct binding measurements show that Cu+2 competes stoichiometrically with the activating ion, Mg+2. A reinterpretation of earlier Mn+2 enolase studies is proposed to reconcile the Cu+2 and Mn+2 data. PMID- 6257841 TI - Quantitative changes in myelin proteins in a peripheral neuropathy caused by Tullidora (Karwinskia humboldtiana). AB - Peripheral nerve demyelination was induced in cats by oral administration of ether extracts of Tullidora (Karwinskia humboldtiana). Proteins from several hindlimb nerves, spinal roots, and dorsal columns of the spinal cord were subjected to slab gel electrophoresis and quantified by densitometry. In Tullidora-treated cats with severe motor disturbances, specific myelin proteins were reduced by at least 50% in motor nerves and less than 25% in cutaneous axons. There was a greater decrease of these proteins in the distal than in the cephalad segments of the sciatic nerve; no changes were detected either in the spinal roots or in the white matter of the spinal cord. Electron microscopy revealed intense demyelination in the motor nerves only. Both the density of the 100 A-thick neurofilaments and the relative proportion of a polypeptide with a molecular weight of 68,000 were considerably increased in the affected nerves. It is tentatively concluded that the active principles of Tullidora may enter the axons through the motor nerve terminals. The distal segments of the motor nerves would then be preferentially affected and demyelination could result from axonal damage. PMID- 6257842 TI - Immunocytochemical localization of (Na+, K+)-ATPase in the goldfish optic nerve. AB - Antiserum to the catalytic subunit of goldfish brain (Na+, K+)-ATPase has been employed at the electron microscopic level by means of the peroxidase antiperoxidase immunohistochemical method. In optic nerve, antigenic sites are restricted to the nodes of Ranvier. No reaction product is detected in underlying internodal neurolemma. Outgrowing neurites for cultured retinal explants devoid of glial ensheathment exhibit a continuous distribution of the enzyme subunit. Antibodies against eel electroplax (Na+, K+)-ATPase cross-react with the goldfish brain enzyme and show a similar immunocytochemical distribution pattern. PMID- 6257843 TI - Differential solubilization of gamma-aminobutyric acid receptive sites from membranes of mammalian brain. AB - Sodium-dependent (+Na) and sodium-independent (-Na) receptive sites for gamma aminobutyric acid (GABA) residing in or on frozen synaptic plasma membranes (SPM) of bovine cerebral cortex were characterized as to binding constants, pharmacologic specificities, and sodium dependence. The SPM fraction was then treated with various concentrations of Triton X-100 resulting in the loss of pharmacologic specificity, binding characteristics, and sodium dependence associated with +Na GABA receptive sites in SPM. The resulting junctional complex preparation (JC), i.e., a fraction enriched in junctional complexes, possessed only the pharmacologic specificity and binding constants associated with -Na receptive sites whether assayed in the presence or absence of 100 mM-NaCl. This is probably due to the detergent dispersal or solubilization of the +Na GABA receptive site. The binding constants, KD and Bmax, for -Na GABA binding in SPM were 170 nM and 4.4 pmol/mg protein, while in JC they were 186 nM and 3.7 pmol/mg protein. Under repeated washing the KD was reduced to 60 +/- 6.9 nM and the Bmax was reduced to 2.5 +/- 0.5 pmol/mg protein in JC, probably owing to the removal of endogenous ligand or inhibitor, and not to inhibition by residual Triton X 100. Multiple extraction with 0.1% or 0.5% Triton X-100 did not alter the KD or Bmax values for the binding of [3H]GABA to JC. Sodium-independent GABA binding was lost from JC membranes with the use of sodium deoxycholate, probably through solubilization. PMID- 6257845 TI - Glial cell markers in the reeler mutant mouse: a biochemical and immunohistological study. AB - The glial cell contents of S100 protein, 2',3'-cyclic AMP, 3'-phosphohydrolase (CNP), isoenzyme II of carbonic anhydrase (CAII) and butyrylcholinesterase (BuChE) were biochemically determined in the cerebellum and cerebrum of the reeler mutant mouse. Astrocytes and oligodendrocytes, shown by this study, contain abnormal amounts of these components. The CAII concentration was significantly increased in the particulate fraction of the reeler cerebellum and cerebrum (by 50% and 89%, respectively). The BuChE specific activity was greatly increased in the reeler, by 120% for cerebellum and by 40% in cerebrum. In contrast, the S100 protein concentration was reduced in the reeler cerebellum by 40% and by 25% in cerebrum, while the CNP specific activity increased by 30% in the reeler cerebellum. In addition, the glial cell distribution was studied by immunohistological techniques with antibodies directed against S100 protein, glial fibrillary acidic protein (GFA) and CAII. Apparently the density of glial cells is not significantly affected. However, the Golgi epithelial cells were usually abnormally placed and their Bergmann fibres were less well developed. PMID- 6257844 TI - In vitro and in vivo binding of S-adenosyl-L-homocysteine to membranes from rat cerebral cortex. AB - Membranes from rat cerebral cortex are able to bind S-adenosyl-L-homocysteine (SAH) with a KD of 5 . 10(-7) M and n of 170 pmol/g fresh tissue (i.e. 20 mg protein). The binding is enhanced by Mg2+ and Ca2+ but not K+ and Na+. gamma Aminobutyric acid, diazepine, noradrenaline and alpha antagonists are without any effect; S-adenosyl-L-methionine, adenosine and adenosine triphosphate inhibit SAH binding. Linkage with an adenosine receptor has not been expressly demonstrated by our method. SAH binding proteins are more abundant in the crude synaptosomal pellet (P2). A similar fixation seems to occur on brain membranes after [3H]SAH administration to rat. The binding might be linked to a methylase activity or an adenosine receptor. PMID- 6257847 TI - Attachment of the synapse-specific phosphoprotein protein I to the synaptic membrane: a possible role of the collagenase-sensitive region of protein I. AB - The purified synapse-specific phosphoprotein Protein I was previously shown to be degraded by a bacterial collagenase, through a series of intermediates, to a collagenase-resistant fragment of molecular weight about 48,000 containing a phosphorylated serine residue. In this study, a purified synaptic membrane fraction containing Protein I was treated with Cl. histolyticum collagenase; membrane-bound and membrane-free proteins were then phosphorylated using [gamma 32P]ATP and analyzed by SDS-polyacrylamide gel electrophoresis and autoradiography. It was observed that Protein I bound to the synaptic membrane was susceptible to the collagenase and degraded to fragments of molecular weights about 68,000, 62,000, and 48,000; the 68,000 fragment remained bound to the membrane whereas the 62,000 and 48,000 fragments were dissociated from the membrane. These observations suggest that the peptide moiety of mol. wt. 6000, present in the 68,000 fragment but absent from the 62,000 fragment, may play a crucial role in anchoring Protein I to the synaptic membrane. PMID- 6257846 TI - [3H]propyl beta-carboline-3-carboxylate binds specifically to brain benzodiazepine receptors. AB - Ethyl beta-carboline-3-carboxylate has recently been isolated from human urine and it was proposed that derivatives of this compound might be related to an endogenous ligand for benzodiazepine receptors. In the present study we investigated high-affinity binding of [3H]propyl beta-carboline-3-carboxylate ([3H]PrCC) to rat brain membranes. [3H]PrCC binds specifically and with high affinity (half-maximal binding at ca. 1nM) to rat brain membranes. The regional and subcellular distributions of specific [3H]PrCC binding are similar, but not identical, to the distributions of [3H]flunitrazepam or [3H]-diazepam binding. The total numbers of binding sites labelled by [3H]PrCC and [3H]flunitrazepam in rat cerebellum are closely similar, and both ligands bind to cerebellar membranes in a mutually exclusive way. The pharmacological selectivity of [3H]PrCC and [3H]diazepam binding is almost identical. Binding of [3H]PrCC like binding of [3H]diazepam, can be increased in vitro by muscimol, GABA and SQ 20.009. Although subtle differences in binding characteristics were observed, these results indicate that [3H]PrCC and benzodiazepines bind to a common recognition site on benzodiazepine receptors. PMID- 6257848 TI - Partial inactivation of Na,K-ATPase in cortical brain slices incubated in normal Krebs-Ringer phosphate medium at 1 and at 10 atm oxygen pressures. AB - Na,K-ATPase (ATP phosphohydrolase EC 3.6.1.3) activity was determined in homogenates of cortical brain slices after incubation in normal Krebs-Ringer phosphate medium at 1 atm oxygen pressure. After 10 min of incubation Na,K-ATPase activity was reduced by approximately 50%. Longer incubation did not cause further change in activity. The presence of 0.1 mM-MnCl2 in the medium offered significant protection, while an excursion to 10 atm oxygen pressure caused further inactivation. Measurements of malonaldehyde levels suggest that the inhibition of Na,K-ATPase is a result of lipid peroxidation. The evidence indicates that brain slices incubated under standard conditions suffer considerable oxidative damage. PMID- 6257849 TI - Chronic hyperphenylalaninemia produces cerebral hyperglycinemia in immature rats. AB - The amino acid content of three tissues was measured in 10-day-old rats made hyperphenylalaninemic from age 3 to 10 days by daily injection of phenylalanine plus alpha-methylphenylalanine to inhibit phenylalanine hydroxylase (PAH). At 12 h after the last injection, the concentrations of alanine, valine, methionine, isoleucine, and leucine in the cerebral hemispheres were depressed by 25-50%, whereas that of glycine was elevated 2.3-fold. In the spinal cord, the levels of phosphoserine, methionine, and leucine were decreased by 40-50%, and those of serine and threonine increased by 50%. Tyrosine and phenylalanine concentrations were high in all tissues, 2-3 and 15-30 times normal, respectively; of the amino acids investigated, they were the only ones changed in the liver. Cerebral hyperglycinemia was also produced by chronic treatment with phenylalanine plus p chlorophenylalanine to inhibit PAH, but not by acute (12 h) hyperphenylalaninemia. An increase in cerebral phosphoserine phosphatase activity was greater in rats treated with phenylalanine plus PAH inhibitor than with inhibitor alone. The content of brain glycine normally declines with age from birth to 15 days; this decrease was prevented by chronic hyperphenylalaninemia. Attempts to reduce the cerebral glycine content of the hyperphenylalaninemic rats were unsuccessful. However, one of the therapeutic protocols, methionine loading, may be useful because it increased the methionine and decreased the phenylalanine contents in the brain. PMID- 6257850 TI - Effect of triethyl tin on myelination in the developing rat. AB - Myelinogenesis in developing rats was studied following chronic dosing with triethyl tin (TET), at a level of 1.0 mg TET/kg body wt/day. Experiments included starved controls with body weights depressed by 17 to 40% to equal those of the TET-treated groups. Rats at ages of 16, 21, and 30 days showed decreases relative to well-nourished controls in body weight, forebrain weight, myelin yield, cerebroside level, and specific activity of brain 2',3'-cyclic nucleotide-3' phosphohydrolase when dosed with TET. At 30 days, myelin and cerebroside yields were reduced by approximately 55%, while CNP activity was reduced by less than 20%. No differences in the forebrain myelin protein composition between control, starved, and TET animals were noted. The rate of myelin protein synthesis relative to brain total protein (assayed by incorporation of intracranially injected [3H]glycine into brain homogenate and myelin proteins) was decreased in the TET rats in proportion to the decreased yield of myelin, but no particular myelin protein was preferentially affected. Matching starved controls exhibited similar body weight decreases, less pronounced forebrain weight decreases, and little or no decrease in myelin concentration. There was a relative increase in the myelin protein synthesis rate in the starved rats, indicating preferential utilization of limited protein precursors for myelin protein synthesis. Spinal cord myelin was also decreased in the TET rats, but less severely than in the forebrain. At all ages optic, but not sciatic, nerves showed decreases in myelin concentration with TET treatment. We conclude that TET inhibits forebrain growth and CNS myelination more severely than can be accounted for by a general metabolic insult. PMID- 6257851 TI - Calcium transport by primary cultured neuronal and glial cells from chick embryo brain. AB - The uptake of calcium was examined in primary cultures of pure neurons and of glial cells from dissociated hemispheres of chick embryo brain. Neuronal cultures took up calcium at a rate of 2.0 nmol per min per mg cell protein at medium concentrations of 1.2 mM-Ca2+ and 5.4 mM-K+. The rate of calcium entry into neurons was increased 2.7-fold by elevating medium potassium to 60 mM. The effect of high external potassium was to increase the Vmax value for calcium transport from 5.5 to 13 nmol per min per mg; the Michaelis constant for calcium, 1.2 mM, was unchanged. The potassium-dependent component of calcium entry into the neuronal cultures was eliminated by addition of 0.1 mM-D-600 (a verapamil derivative) or by 1 mM-CoCl2, but 0.5 microM-tetrodotoxin had no significant effect. When choline replaced potassium in uptake medium no change in calcium transport was detected in neurons, nor was the entry of calcium increased when choline replaced sodium. Glial cultures took up calcium at 20% of the basal rate for neuronal cultures on a weight-of-protein basis. Uptake was not increased by potassium; during depolarization by potassium the calcium transport activity of glia was less than 10% that of neurons. It was concluded that cultured neurons contain a depolarization-sensitive, calcium-specific channel. A similar calcium transport activity was not detected in cultured glial cells. PMID- 6257852 TI - Change of cycle AMP level in synaptosomes from cerebral cortex; increase by adenosine derivatives. AB - The endogenous level of cyclic AMP in incubated synaptosomes from cerebral cortex of guinea pigs was investigated after the addition of various agents to the incubation medium. It appeared that the synaptosomal suspension already contained exogenous adenosine. Preincubation with theophylline or with adenosine deaminase (ADase) decreased both the exogenous level of adenosine and the intrasynaptosomal level of cyclic AMP. The level of cyclic AMP was reincreased by the addition of adenosine agonists, especially 2-chloroadenosine. This increase was antagonized by deoxyadenosine and was not inhibited by dipyridamole. These results suggest that the adenosine derivatives in the synaptic cleft regulate the level of cyclic AMP in nerve terminals through adenosine receptor on the presynaptic membrane. ADP, ATP, dopamine, and histamine also stimulate the formation of cyclic AMP in the ADase-treated synaptosomes. PMID- 6257853 TI - Neutral glycosphingolipids and ceramide composition of ethylnitrosourea-induced rat neural tumors: accumulation of ceramide in tumors. AB - Experimental rat neural tumors in offspring were induced transplacentally by a single injection of a chemical carcinogen, ethylnitrosourea, 20 mg/kg body weight, in the tail vein of the mother. The neutral glycosphingolipid, sulfatide, and ceramide composition of the tumors and the normal tissues from which the tumors originated is described. The content of nonhydroxy fatty acid (NFA) and hydroxy fatty acid (HFA) containing ceramide in all the neural tumors so far examined was significantly increased compared with the corresponding normal neural tissue. Some 8 to 18 mol% of total neutral glycolipids was as ceramide in neurinomas, oligodendrogliomas, and meningiomas. Lactosylceramide in normal neural tissues was about 1 mol% of the total neutral glycosphingolipids. In various neural tumors lactosylceramide increased up to 8 mol%. NFA- and HFA containing cerebrosides constitute 94-100% of the neutral glycosphingolipids in normal neural tissues. In various neural tumors the mol percent of cerebrosides was significantly reduced. A high performance liquid chromatographic method was modified to analyze simultaneously ceramides, cerebrosides, and higher neutral glycosphingolipids. PMID- 6257854 TI - Correlations between Na+-K+ ATPase activity and acetylcholine release in rat cortical synaptosomes. AB - [3H]Acetylcholine efflux and Na+-K+ ATPase ion pump activity were measured concomitantly in rat cortical synaptosomes. Ouabain (500 microM), strophanthidin (500 microM), and parachloromercuribenzene sulfonate (500 microM) each inhibited ouabain-sensitive 86Rb uptake and elevated [3H]acetylcholine release independently of the external calcium concentration. Veratridine (10 microM), electrical field stimulation (60 V, 60 Hz, 5-ms pulse duration), or the calcium ionophore A23187 (10 micrograms/ml) also inhibited ouabain-sensitive 86Rb uptake and released [3H]acetylcholine, but via a calcium-dependent process. Veratridine induced [3H]acetylcholine release and ion pump inhibition were correlated over a wide range of drug concentrations and both effects were blocked by pre-treatment with tetrodotoxin (1 microM). The rate of [3H]acetylcholine efflux from superfused synaptosomes was increased within 15 s of exposure to ouabain, strophanthidin, veratridine, A23187, or field stimulation, while ouabain sensitive 86Rb uptake was significantly decreased within a similar interval. These results suggest that [3H]acetylcholine release is due at least in part to inhibition of Na+-K+ ATPase. PMID- 6257855 TI - Polypeptide hormones and chromatin-associated proteins act as acceptors for cholera toxin-catalyzed ADP-ribosylation. AB - Cholera toxin catalyzed the ADP-ribosylation of the pituitary protein hormones thyrotropin (TSH), lutropin (LH), follitropin (FSH), human chorionic gonadotropin (hCG), and corticotropin (ACTH)1-24, and ADP-ribosylation of the basic proteins histone subfraction H1 and protamine. Casein and phosvitin, acidic nuclear proteins, did not act as acceptors for toxin-catalyzed ADP-ribosylation. The isolated TSH A and B subunits were tested for their ADP-ribose acceptor activity. The TSH A subunit showed fourfold greater ADP-ribose acceptor activity than the TSH B subunit. The ADP-ribose acceptor protein protamine was analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis following incubation with cholera toxin under ADP-ribosylating conditions. [3H]ADP-ribose incorporated into protein from [3H]NAD migrated with the acceptor protein protamine. In the absence of added acceptor protein, the [3H]ADP-ribose incorporated into protein migrated with the A1 fragment of cholera toxin. Cholera toxin A and B subunits were isolated and tested for their ability to catalyze the transfer of ADP-ribose to protamine. The cholera toxin A subunit showed 50-fold greater ADP ribosyltransferase activity than the B subunit. Our data indicate that a variety of adenohypophyseal hormones and regulatory proteins act as acceptors for toxin catalyzed ADP-ribosylation. These studies may help in understanding the role of endogenous ADP-ribosyltransferases and the physiological effects of this modification of protein. PMID- 6257856 TI - Opioids, noradrenaline and GTP analogs inhibit cholera toxin activated adenylate cyclase in neuroblastoma x glioma hybrid cells. AB - D-Ala2-Met5-enkephalin, morphine, and noradrenaline inhibit the adenylate cyclase in homogenates of neuroblastoma x glioma hybrid cells in a dose-dependent manner even after the enzyme has been preactivated by cholera toxin. Half-maximal inhibition and extent of inhibition are the same with native or cholera toxin activated enzyme. The inhibition caused by opioids or noradrenaline are antagonized by naloxone or phentolamine, respectively. The effect of D-Ala2-Met5 enkephalin on cholera toxin-activated enzyme is immediate in onset and rapidly reversed by the addition of naloxone. Guanyl-5'-yl-imidodiphosphate stimulates basal activity but inhibits the enzyme activated by cholera toxin or prostaglandin E1. Stimulation occurs at a concentration of 100 microM or above, inhibition even at 0.1 microM. The inhibitory effect of the non-hydrolysable GTP analog is antagonized by GTP. Guanyl-5'-yl-methylenediphosphonate, another nonhydrolysable GTP analog, inhibits basal as well as cholera toxin-stimulated or prostaglandin E1-stimulated adenylate cyclase. Other guanine derivatives such as GDP, GMP, cyclic GMP, guanyl-5'-yl-phosphoric acid amide and guanosine have no effect under the same conditions. The results may be taken as a piece of evidence for two separate guanyl nucleotide-binding sites accompanying the adenylate cyclase in the hybrid cells and mediating, respectively, stimulation and inhibition of the enzyme by hormones. PMID- 6257857 TI - Rapid incorporation in vivo of intracerebrally injected 32Pi into polyphosphoinositides of three subfractions of rat brain myelin. AB - At intervals ranging from 1 to 10 min after injection of 32Pi into rat brain, myelin was prepared and separated into three subfractions: heavy, medium, and light. The radioactivity of total phospholipids and polyphosphoinositides (PPI) was then determined. There was rapid incorporation of 32Pi into PPI, which contained 50-70% of the radioactivity among total brain lipids and more than 70% among myelin lipids. The myelin fraction had incorporated 32Pi into total recovered PPI in the order of medium greater than heavy greater than light fraction; however, the order of relative specific radioactivities was heavy greater than light greater than medium. Labeling of the PPI precursors, phosphatidic acid (PA) and phosphatidylinositol (PI), was considerably lower in the purified myelin than in total brain. The di- (DPI) and triphosphoinositides (TPI) in heavy myelin exchanged 32Pi rates 2 to 3 times faster than those in medium and light myelin. DPI of all subfractions of myelin exchanged much faster than TPI. The results show that the most active phosphate turnover of myelin PPI occurs in the heavy myelin fraction (probably largely consisting of myelin appurtenant regions). However, medium and light myelin (most probably representing the closely packed layers of myelin sheaths) also showed rapid turnover of PPI. PMID- 6257858 TI - Purification of rat 2',3'-cyclic nucleotide 3'-phosphodiesterase. AB - 2',3'-Cyclic nucleotide 3'-phosphodiesterase (CNP, EC 3.1.4.37) has been isolated from rat brain myelin by chromatography on successive columns of phenyl-Sepharose CL-4B, CM-Sepharose CL-6B, and 8-(6-aminohexyl) amino-2'AMP-Sepharose 4B. From 15 g of rat brain, approximately 400 micrograms of pure CNP was obtained, with a specific activity of 1,200 (2',3'-cyclic AMP) units/mg protein. The Km of the rat enzyme was 3.7 mM, using 2',3'-cAMP as the substrate. Isoelectric focusing of the enzyme indicated a broad isoelectric range of 8.5-9.0. On SDS polyacrylamide gels, rat CNP appears as two protein bands of approximately 48,000 and 50,000 M.W., with an upper band intensity of about 1/10 that of the lower band. The relative intensities of the bands for CNP and the molecular weights correspond to the Wolfgram proteins W1 and W2 described by other investigators. The amino acid analysis of the purified rat enzyme compared favorably with reported determinations for the bovine enzyme and also with reported values for the rat Wolfgram proteins W1 and W2. PMID- 6257859 TI - High-affinity [3H]choline accumulation in cultured human skin fibroblasts. AB - [3H]Choline can be transported across cell membranes by high-affinity (KT less than 5 microM) and low-affinity (KT much greater than 5 microM) systems. High affinity choline accumulation (HACA) has been demonstrated in synaptosomes made from cholinergic brain regions such as the hippocampus and caudate-putamen. In cell culture, HACA has been demonstrated in glia and avian telencephalon, dissociated spinal cord, and muscle fibroblasts. We examined [3H]choline accumulation in a single normal human fibroblast line cultured from skin biopsy. [3H]Choline accumulation was temperature-dependent and linear with incubation time up to 6 min at 0.125 microM-choline. The apparent KT for [3H]choline was 5 microM, which is similar to that observed in avian fibroblasts. Isoosmotic replacement of Na+ with either Li+ (144 mM) or sucrose (288 mM) severely reduced [3H]choline accumulation (by 70-90%). Pre-incubation with ouabain (100 microM), sodium orthovanadate (100 microM), or 2,4-dinitrophenol (100 microM), or replacement of Ca2+ by Mg2+ had little or no effect on subsequent [3H]choline accumulation. [3H]Choline accumulation was inhibited by hemicholinium-3 (HC-3); after pre-incubation in HC-3 at 37 degrees C for 10 min, the IC50 (at 0.125 microM-choline) was 5.6 microM. The HC-3 sensitivity, Na+ dependence, and low KT suggest that human skin fibroblasts have a high-affinity transport system for choline. PMID- 6257860 TI - Alterations in dihydromorphine binding in cerebral hemispheres of aged male rats. AB - Equilibrium binding of [3H]dihydromorphine was assayed in brain regions of young and aged male F344 rats. Young rats had significantly higher receptor densities than old rats in the frontal poles, anterior cortex, and striatum. In the frontal poles, the decline in receptor concentration with age was accompanied by a significant increase in the apparent affinity of dihydromorphine for receptors, which may be compensatory for the decrease in Bmax. This pattern of receptor alterations is different than that previously observed in aged female rats. Therefore, processes which underlie synaptic alterations with age may be different in males and females. PMID- 6257862 TI - Population of quickly adapting mechanoreceptive afferents innervating monkey glabrous skin: representation of two vibrating probes. PMID- 6257861 TI - Functional properties of neurons in cat trigeminal subnucleus caudalis (medullary dorsal horn). II. Modulation of responses to noxious and nonnoxious stimuli by periaqueductal gray, nucleus raphe magnus, cerebral cortex, and afferent influences, and effect of naloxone. PMID- 6257863 TI - Interneurons involved in mediation and modulation of gill-withdrawal reflex in Aplysia. II. Identified neurons produce heterosynaptic facilitation contributing to behavioral sensitization. PMID- 6257864 TI - Interneurons involved in mediation and modulation of gill-withdrawal reflex in Aplysia. III. Identified facilitating neurons increase Ca2+ current in sensory neurons. PMID- 6257865 TI - The effect of severe hypoglycemia upon cerebrospinal fluid formation, ventricular iodide clearance, and brain electrolytes in rabbits. AB - Severe insulin-induced hypoglycemia in rabbits reduces cerebrospinal fluid (CSF) formation, but not ventricular iodide clearance as measured by ventriculocisternal perfusion. This indicates that CSF production is ultimately glucose-dependent but that ventricular iodide clearance is not. The data suggest that severe hypoglycemia results in intracellular potassium loss within the brain and show that extracellular sodium replaces lost intracellular potassium. Hypoglycemia probably results in cellular adenosine triphosphate (ATP) reduction which affects membrane Na/K ATPase and the ability of the brain cell to maintain a potassium gradient. Potassium levels in the CSF also rise consequent to hypoglycemia. Homeostatic mechanisms that maintain a constant CSF potassium, therefore, are also affected by hypoglycemia. PMID- 6257866 TI - Influence of diet composition on serum triiodothyronine (T3) concentration, hepatic mitochondrial metabolism and shuttle system activity in rats. AB - Two experiments were conducted to determine if variations in diet composition sufficient to alter circulating triiodothyronine (T3) concentration would influence hepatic mitochondrial metabolism. In experiment 1, mitochondrial respiration and the activity of succinate dehydrogenase (SDH), cytochrome oxidase (CO) and alpha glycerophosphate dehydrogenase (m alpha-GPD) were measured in 42 day-old male rats fed diets containing casein/carbohydrate/fat: 8/73/10% (low protein), 22/59/10% (control protein), and 45/36/10% (high protein) for 3 weeks. When compared to control, serum T3 was increased 2-3 times in the low and decreased 19% in the high protein-fed groups. Mitochondria isolated from low protein-fed rats consumed less oxygen in both state 4 and state 3 with succinate as substrate when compared to control or high protein fed rats. However, ADP/O and respiratory control (RC) ratios were similar in all groups. Activity of SDH and CO was decreased only in low protein-fed rats. M alpha-GPD activity was increased in the low and decreased in the high protein fed-rats. In experiment 2, alpha-glycerophosphate shuttle activity was increased 2-3 fold and malate aspartate shuttle activity decreased 60% in intact mitochondria isolated from low protein-fed rats when compared to rats pair-fed control diet. These results suggest a role for diet composition as a regulator of hepatic intermediary metabolism mediated by thyroid hormones. PMID- 6257867 TI - Neutral detergent fiber, hemicellulose and cellulose digestibility in human subjects. AB - The fate of dietary fiber and its components was examined in seven women consuming low cellulose (LC) and high cellulose (HC) diets, each for about 1 month. The diets were of constant daily composition and differed only in that the HC diet contained an additional 16 g/day non-nutritive fiber (Solka Floc), which increased the neutral detergent fiber (NDF) of the diet from 9.5 to 23.5 g/day and Crampton and Maynard cellulose from 5.4 to 19.3 g/day. When apparent fiber digestibilities during 5-day periods were determined, both NDF and cellulose digestibilities varied greatly and inconsistently in each subject throughout both diet periods. Therefore, samples were pooled to form a single 20-30 day composite for each subject during each diet. Mean apparent NDF digestibility, after correcting for protein contamination in fecal NDF, was 70.4 +/- 7.3% during the LC diet and decreased to 23.0 +/- 15.0% during the HC diet. Cellulose digestibility was 69.7 +/- 10.7% without and 15.7 +2- 17.4% with the added cellulose. Hemicellulose was calculated as NDF minus cellulose. When the fecal NDF was corrected for protein contamination, hemicellulose digestibility averaged 71.7 +/- 5.4% during the LC diet and 51.0 +/- 7.9% during the HC diet. In a separate experiment, 16 g/day Solka Floc was ingested with a semi-purified liquid diet and only 8% of the cellulose was digested. These results suggest that more than half of the fiber in a LC diet containing fruits, vegetables and refined grains is degraded, while the apparent digestibility of refined cellulose is minimal. PMID- 6257868 TI - Calcium metabolism in the young adult male as affected by level and form of phosphorus intake and level of calcium intake. AB - A 60-day human metabolic study was conducted to measure polyphosphate hydrolysis and to compare the effects of supplements of phosphorus from ortho- and polyphosphates as well as supplements of both calcium and orthophosphates on calcium metabolism. The experiment was arranged in a 4 x 4 latin square design with eight subjects and four 15-day dietary periods. During its passage through the digestive tract, the polyphosphate supplement was 80.5 +/- 5% hydrolyzed to orthophosphate. Calcium absorption was significantly lower when the polyphosphate supplement was given than when the orthophosphate supplement was given. Both forms of phosphate caused a reduction in fractional renal tubular reabsorption of calcium, but only the orthophosphate supplement improved calcium balance. Calcium equilibrium was achieved, however, only when supplements of both calcium and orthophosphate were given. Both phosphorus supplements caused an increase in urinary cyclic AMP, indicating an increase in parathyroid hormone (PTH) secretion, but bone resorption as measured by urinary hydroxyproline was not affected by either phosphate supplement. The combined supplement of calcium and orthophosphate, however, caused decreases in the excretion of both cyclic AMP and hydroxyproline, suggesting a decrease in PTH-mediated bone resorption. PMID- 6257869 TI - Effects of quantity and quality of dietary protein on certain enzyme activities in rainbow trout. AB - The effects of variation in quality and quantity of dietary protein on certain tissue enzymes in rainbow trout (Salmo gairdneri) were examined. Trout were given for 9 weeks diets containing proteins of different quality (fish-meal, casein and corn gluten) and with protein energy levels ranging from 26 to 74% of total metabolizable energy. In the first experiment, activities of a number of enzymes were monitored by only hepatic serine pyruvate transaminase (SPT) activity changed in response to the dietary treatments--increasing as protein energy level was raised. In the second experiment, opposing glycolytic an gluconeogenic enzyme activities [pyruvate kinase (PK) and phosphoenolpyruvate carboxykinase (PEPCK); phosphofructokinase (PFK) and fructose diphosphatase (FDP)] were measured. Gluconeogenic enzyme activities correlated positively and significantly with dietary protein energy level; glycolytic enzymes correlated negatively and significantly with this parameter for all three proteins. There was no consistent relationship between presumed equilibrium point of opposing enzyme activities and maximum weight gain for the three proteins. It is suggested that hepatic activities of SPT, PFK, PK, FDP and PEPCK will provide useful indices of protein status in trout. PMID- 6257870 TI - Occurrence of vitamin D sulfate in human milk whey. AB - Following reports that vitamin D sulfate is the major source of vitamin D activity in human milk, we investigated the presence of this compound in milk whey using a modification of techniques for the determination of vitamin D metabolites in plasma. Synthetic cholecalciferol sulfate, ergocalciferol sulfate an [3H]cholecalciferol sulfate were prepared by reacting radioactive cholecalciferol or nonradioactive cholecalciferol or ergocalciferol with sulfamic acid in pyridine. The products were purified sequentially by Sephadex LH-20 and high pressure liquid chromatography. The purified products were chromatographically homogeneous, exhibited an ultraviolet absorption spectrum identical to that of standard cholecalciferol, demonstrated a sulfonate ester linkage and upon saponification yielded the parent vitamin. Milk whey was extracted with methanol:methylene chloride (1:2 v/v) using [3H]cholecalciferol sulfate to estimate recovery of the compound. The extract was purified by chromatography on silica cartridges an reverse phase high pressure liquid chromatography and was quantitated by ultraviolet absorption (UV). Although added cholecalciferol sulfate was readily detected in human milk whey samples, no endogenous vitamin D sulfate was found (detection limit 1 ng/ml). The results indicate that vitamin D sulfate is not a major source of vitamin D activity in human milk. PMID- 6257871 TI - Effects of vitamin B-6 deficiency and 4'- deoxypyridoxine on pyridoxal phosphate concentrations, pyridoxine kinase and other aspects of metabolism in the rat. AB - Male rats about 100 days old were fed a B-6 deficient diet supplemented with 4' deoxypyridoxine (1 g/kg diet) and/or pyridoxine hydrochloride (22 mg/kg diet) for 30 to 35 days. Addition of 4'-deoxypyridoxine to the B-6-deficient diet produced greater losses in body weight (P less than 0.05) and thymus weight (P less than 0.01) than in B-6-deficient pair-fed controls. 4'-Deoxypyridoxine combined with a B-6-deficient diet produced no decreases in the concentration of pyridoxal phosphate or pyridoxine kinase in the tissues examined when compared with B-6 deficient controls. Addition of deoxypyridoxine to a diet containing adequate B-6 tended to reduce that absolute weight of the adrenal glands and increased (P less than 0.05) plasma cholesterol compared with animals receiving only vitamin B-6. Compared with the B-6-deficient groups, pyridoxal phosphate concentrations in animals receiving normal B-6 were significantly (P less than 0.01) increased in the liver, muscle and adrenal glands but not in the thymus. In all groups the pyridoxine kinase activity was highest in the adrenal glands (3.6-6.3 pmole pyridoxine phosphate/minute/mg tissue) followed by the liver (1.3-3.7) and thymus (0.7-1.3). These high kinase values and the weight changes suggest an important role for vitamin B-6 in these organs. Recent evidence that pyridoxal phosphate may interact with glucocorticoid receptors raises the possibility that the role of vitamin B-6 in these and other organs may involve metabolic regulation by a mechanism independent of the well-established coenzyme function of this vitamin. PMID- 6257873 TI - [Pleomorphic adenoma of the nasal septum: report of two cases and review of Japanese literature (author's transl)]. PMID- 6257872 TI - Aggressive fibrous histiocytoma of perioral soft tissues: report of case. AB - A rare case of aggressive fibrous histiocytoma is presented to alert the clinician to the existence of such a lesion and its ability to develop as a perioral soft tissue tumor. The research on these lesions clearly demonstrates the lability of their biologic potential. The clinical characteristics, symptoms, and histiologic makeup are reviewed and further reinforce the conclusion that careful microscopic study and thorough longterm followup to adequate surgical treatment are currently the only effective means in the management of these tumors. Continued reports from clinicians and researchers will perhaps satisfy many questions concerning this curious and potentially destructive and lethal group of lesions. PMID- 6257874 TI - Chronic pain: principles of management. PMID- 6257875 TI - Hyperphosphatemia with insufficient parathyroid response in renal failure. PMID- 6257876 TI - Fatal Epstein-Barr virus-associated hemophagocytic syndrome. PMID- 6257877 TI - Prevention of transfusion-acquired cytomegalovirus infections in newborn infants. AB - Transfusion-acquired cytomegalovirus infections occurred in 13.5% of 74 infants of seronegative mothers who were exposed to one or more blood donors who had a CMV indirect hemagglutination titer of 1:8 or higher. None of 90 infants of seronegative mothers exposed only to donors with CMV IHA titers of less than 1:8 became infected. Ten of 41 (24%) infants of seronegative mothers who received more than 50 ml of packed red blood cells and who were exposed to at least one seropositive donor became infected. None of 23 infants of seronegative mothers who received this amount of blood but who were exposed only to seronegative donors became infected. Fatal or serious symptoms developed in 50% of the infected infants of seronegative mothers and in none of the 32 infected infants of seropositive mothers. Acquired CMV infections occurred in 15% of infants of seropositive mothers who were exposed to the red blood cells of seropositive donors and in 17.6% of infants of seropositive mothers exposed only to seronegative donors. Use of seronegative donors reduced the prevalence of excretion of CMV among hospitalized infants who were 4 weeks of age or older from 12.5 to 1.8% and eliminated acquired CMV infections in infants of seronegative mothers. PMID- 6257879 TI - Hormonal enhancement of technetium-99m pertechnetate uptake in experimental Meckel's diverticulum. AB - A canine model simulating Meckel's diverticulum was used to evaluate the effects of pentagastrin, glucagon, and a combination of the two hormones on the gastrointestinal localization of 99mTc. Pentagastrin produced accelerated uptake of the radionuclide in both the stomach and the ectopic gastric mucosa but resulted in early visualization of the duodenum and a "washout" effect on the radioisotope within the Meckel's diverticulum. Glucagon provided prolonged retention of the radionuclide in the stomach and ectopic mucosa and prevented duodenal visualization. A combination of both hormones produced increased activity in the stomach and experimental Meckel's and decreased duodenal filling. This enhanced target to background contrast and provided improved visualization of the ectopic gastric mucosa. PMID- 6257878 TI - Incorporation of glucose carbon into ribonucleotides of axenic Entamoeba histolytica. AB - Axenic Entamoeba histolytica grown with (UL-14C)glucose in TP-S-1 medium were capable of biosynthesizing ribose from labeled glucose. RNA isolated by phenol extraction was hydrolyzed to the ribonucleotide level by alkaline hydrolysis. The hydrolysate, chromatographed on ion exchange resins, yielded AMP, GMP, and UMP, but not CMP containing labeled glucose carbon. The present nucleotide composition of the isolated amebal RNA was, respectively, as follows, CMP, 0.20; GMP, 0.22; AMP, 0.30; UMP, 0.29. The location of all the radiolabel in each ribonucleotide was the ribose moiety. The relative specific incorporation of glucose carbon into AMP, GMP, and UMP was 0.47, 0.05, and 0.10, respectively. These results suggest that the bulk of amebal nucleic acid precursors are obtained as preformed nucleosides and/or nucleotides from TP-S-1 medium. The mean RNA content per milliliter packed cells of amebae was 4.2 +/- 0.2 mg. PMID- 6257880 TI - Improvement of diabetic symptoms of hereditary diabetic (KK) mice by a single injection with islet-activating protein (IAP). AB - Islet-activating protein (IAP) prepared from the culture medium of Bordetella pertussis cells was very effective in eliminating diabetic symptoms characteristic of hereditary diabetic KK mice over a long period of time. After a single injection of IAP (5 microgram/kg body wt) into KK mice, the non-fasting concentration of blood glucose was maintained nearly normal over 2 weeks, with a gradual return to the pre-IAP level 30 days later. During this period, glucose tolerance was normalized and only few animals excreted glucose in urine. The second injection of IAP to these diabetic mice caused a more prolonged restoration of normoglycemia. When KK mice had been injected with IAP, they responded to epinephrine and isoproterenol more readily than did ddY mice in increasing plasma insulin and glycerol. PMID- 6257881 TI - The effects of amrinone on transport and cyclic AMP metabolism in toad urinary bladder. AB - Amrinone is a new noncatechol, nonglycoside agent with cardiotonic and vasodilator properties. This paper examines the effects of amrinone in the toad urinary bladder, a tissue whose function may be altered by many factors which also change cardiovascular activity. Amrinone enhanced the effect of vasopressin and cyclic AMP on water and urea permeabilities, as well as the effect of vasopressin on sodium transport. Consistent with these actions, amrinone inhibited cyclic AMP phosphodiesterase activity in epithelial homogenates and increased both cyclic AMP content and the protein kinase activity ratio measured in intact epithelial cells. The inhibitory effect of amrinone on phosphodiesterase may be relevant to its cardiostimulatory and vasodilator activities. PMID- 6257882 TI - Antihypertensive activity of captopril (SQ 14,225), an orally active inhibitor of angiotensin converting enzyme in conscious two-kidney perinephritic hypertensive dogs. AB - Conscious dogs made hypertensive by wrapping both kidneys with cellophane were treated daily with a single dose of captopril (31 mg/kg p.o.), an inhibitor of the angiotensin converting enzyme, or with placebo (lactose, 31 mg/kg p.o.) for a period of 13 weeks. Blood pressures were recorded indirectly from a forepaw by using a Roche ultrasonic pressure transducer (Arteriosonde). Treatment with captopril resulted in decreases in blood pressure (25-30 mm Hg) that were maximal at 3 to 6 hr with no associated changes in heart rate. The captopril-induced hypotensive effect was maintained throughout the 13-week treatment period, and after the termination of captopril dosing, pressure rose slowly over the next 72 hr to a level not significantly different from placebo-treated dogs. Plasma renin activity (PRA) in the hypertensive dogs at the time treatment was initiated was not different from the same animals when they were normotensive. In captopril treated animals, PRA increased 3- to 4-fold after each dose of the drug was given, reaching a maximum at 3 to 6 hr, a time corresponding to the maximal blood pressure decrease. PRA gradually declined but did not reach control levels before the next dose of captopril was administered. In animals treated with placebo, PRA remained at levels not significantly different from normotensive dogs during the entire treatment period. After termination of captopril administration, PRA slowly returned to pretreatment levels; the return of PRA paralleled the recovery of blood pressure. The results indicate that captopril is effective in reducing blood pressure for an extended period of time in a hypertensive model in which the level of activity of the renin angiotensin system is not elevated. PMID- 6257883 TI - The cardiovascular and autonomic effects of repeated administration of delta-9 tetrahydrocannabinol to rhesus monkeys. AB - The cardiovascular effects of repeated dosing with delta-9-tetrahydrocannabinol (THC) were examined in chronically catheterized, conscious rhesus monkeys. THC (0.5 mg/kg) was administered i.v. every 6 hr for 3 weeks. Following the first THC bolus, a tachycardia (peak change, 34 beats/min) and hypotension (peak change, 21 mm Hg systolic blood pressure) sometimes preceded by a transient blood pressure increase were observed. Tolerance developed to the tachycardia and systolic blood pressure increase but not to the blood pressure decrease. Hourly measurement of systolic blood pressure and heart rate during the intervals between injections revealed heart rate decreases to which tolerance developed and blood pressure decreases which were sustained throughout the course of TCH dosing. Urinary catecholamine excretion increased during the 1st week of dosing and subsequently returned toward base-line levels. Control of basal heart rate and reflex heart rate changes was examined using autonomic agonists and antagonists. Heart rate decreases after beta adrenergic blockage (sotalol HCl) were attenuated, whereas heart rate increases after cholinergic blockade (atropine methylnitrate increases after cholinergic blockade (atropine methylnitrate) were augmented. Baroreceptor gain, measured as the ratio of heart rate change to systolic blood pressure change in response to phenylephrine, increased. The response of basal heart rate to antagonists and the augmented reflex bradycardia suggest that THC alters autonomic control of the cardiovascular system resulting in parasympathetic dominance. Divergent patterns of development of tolerance to heart rate and blood pressure effects suggest that THC affects heart rate and blood pressure through different mechanisms. PMID- 6257885 TI - Modification of spinal cord transmission by an interaction of chlorpromazine and phenytoin. AB - Cat spinal cord monosynaptic activity during slow repetitive stimulation (0.2 Hz) and post-tetanic potentiation was used to evaluate the combination effects of phenytoin and chlorpromazine. The drug effects were compared in anesthetized cats with either high spinal transection or intact central nervous systems to determine whether the drugs were acting segmentally or suprasegmentally. When chlorpromazine and phenytoin were given in combination to intact animals, the depressant effect on the monosynaptic response was limited to 50% of control, which was not more than the maximum effect of either drug given alone. In spinal animals, chlorpromazine reversed the phenytoin-induced depression during 0.2 Hz stimulation, whereas only the effects of phenytoin on post-tetanic potentiation were evident after the drug combination. These results show that although phenytoin and chlorpromazine each have a depressant effect on spinal cord transmission, the combined effect is limited to a 50% decrease in intact animals. It is suggested that this occlusive drug effect demonstrates that the drug combination has a limited depressant action in the intact nervous system, an action which permits the expression of the effects of these drugs on the other elements of the reflex arc. Collectively, these actions of the drug combination are consistent with their known efficacy in treating certain cases of spasticity. PMID- 6257884 TI - Beta-1 receptor mediation of renin secretion elicited by low-frequency renal nerve stimulation. AB - The purpose of this study was to determine if renin secretion resulting solely from low-frequency renal nerve stimulation (no change in renal blood flow or urinary sodium excretion) is mediated by activation of beta-1 (beta-1) or beta-2 (beta-2) adrenergic receptors. Beta-1 and beta-2 adrenergic receptor blockade were produced with atenolol and butoxamine, respectively. Low-frequency renal nerve stimulation (0.5 Hz) increased renin secretion without altering mean arterial pressure, renal blood flow, glomerular filtration rate or urinary sodium excretion. The increase in renin secretion in response to renal nerve stimulation was blocked by beta-1 blockade with intrarenal atenolol (2.0 micrograms/kg/min) infusion. This dose of atenolol reduced the renal vasodilator response to intrarenal isoproterenol by only 48%, thus indicating modest beta-2 receptor blockade. A lower dose of atenolol (30 micrograms/kg i.v.) markedly decreased the tachycardia in response to i.v. isoproterenol (2 micrograms) but had no effect on the renal vasodilator response to intrarenal isoproterenol injection (2 micrograms), thus indicating selective beta-1 blockade. This dose of atenolol abolished the increase in renin secretion during renal nerve stimulation. In contrast, beta-2 receptor blockade with butoxamine (20 micrograms/kg/min) did not alter the renin secretion response to renal nerve stimulation. This dose of butoxamine decreased the renal vasodilator response to intrarenal isoproterenol by 73%, thus demonstrating significant beta-2 receptor blockade. These results indicate the low-frequency renal nerve stimulation (0.5 Hz) increases renin secretion without altering renal hemodynamics or urinary sodium excretion. This neurally mediated renin secretion resulted from activation of beta-1 adrenergic receptors. PMID- 6257886 TI - Intrastriatal kainic acid: acute effects on electrophysiological and biochemical measures of nigrostriatal dopaminergic activity. AB - The acute effects of intrastriatal kainic acid injection in nigrostriatal dopamine cell activity were assessed using electrophysiological and biochemical techniques. One hour after kainic acid injection, dopamine cell firing rates were significantly increased, as were striatal dopamine synthesis (dopa accumulation) and dopamine metabolism (3,4-dihydroxyphenylacetic acid levels). Twelve hours postkainic acid administration, cell firing rate had returned to control levels, as had dopa accumulation and DOPAC levels, but the number of dopamine cells firing had significantly decreased. Action potentials were elicited from the "silent" dopamine cells by iontophoretic application of gamma-aminobutyric acid but not glutamate. Conversely, 48 hr after kainic acid, the number of dopamine cells firing was significantly increased, as were 3,4-dihydroxyphenylacetic acid levels. Both cell firing rate and dopa accumulation, however, matched control values. The results are discussed in terms of the role of strionigral pathways in mediating the acute effects of kainic acid on the nigrostriatal dopaminergic system and are interpreted in light of the recently described phenomenon of presumed dopamine cell depolarization inactivation. PMID- 6257887 TI - A comparative study on the effects of morphine on central, peripheral and ganglionic stores of catecholamines. AB - The turnover and metabolism of catecholamines after i.p. administration of 10 (low dose) or 40 (high dose) mg/kg of morphine sulfate were measured in the brain, lumbar spinal cord, heart, celiac and superior cervical ganglia (SCG) of demedullated rats with unilaterally decentralized SCG. Demedullation significantly increased norepinephrine concentration and turnover in both sham operated and decentralized SCG, but demedullation failed to change the turnover of dopamine (DA) in both ganglia. Low doses of morphine only increased DA metabolism in the caudate nucleus. High doses of morphine failed to change the turnover of norepinephrine stored in heart and sympathetic ganglia but produced variable changes in norepinephrine turnover in the spinal cord and brain. High doses of morphine significantly increased DA turnover and metabolism in the celiac ganglion, SCG, caudate nucleus and the spinal cord of demedullated rats. These effects of morphine were antagonized by naloxone. DA metabolism in decentralized SCG of demedullated and SCG of intact rats remained unchanged after high doses of morphine. The action of morphine on DA metabolism was facilitated by demedullation, suggesting that the adrenal medulla secretes a modulator that can counteract the effects of opiate ligands on ganglionic small intensely fluorescent cells. Atropine and hexamethonium failed to antagonize the increase in the metabolism of ganglionic DA produced by morphine; and the increase in ganglionic DA metabolism caused by oxotremorine was not antagonized by naloxone, thus confirming a disassociation between the action on ganglionic DA mediated by cholinergic and opiate receptors. Since decentralization of the SCG abolishes the increase in DA metabolism induced by morphine, stimulation of extraganglionic opiate receptors reflects the metabolism of DA located in small intensely fluorescent cells. PMID- 6257888 TI - Quinacrine-blocked desensitization of adrenoceptors after immobilization stress or repeated injection of isoproterenol in rats. AB - Repeated forced immobilization or repeated administration of isoproterenol reduces the number of beta adrenoceptors in the heart and spleen of rats. Isoproterenol, but not immobilization, reduced the number of beta receptors in the lung. These changes in beta adrenoceptors were prevented by administration of quinacrine, a phospholipase A2 inhibitor, although the drug had no effect on beta adrenoceptors when given alone. Immobilization, but not isoproterenol, reduced the number of alpha-1 adrenoceptors in the heart but had no effect on the lung. Quinacrine treatment decreased the number of alpha-1 receptors in heart and lung but increased alpha-2 receptors in the spleen. The changes in receptor number attending exposure to agonists are usually consistent with the expected changes. The effects of quinacrine on such changes suggest that phospholipids are involved in modulating the changes in number of receptors or their availability to interact with ligands. PMID- 6257889 TI - On the use of a dynamic approach to the estimation of dissociation constants for reversible competitive antagonists. AB - A dynamic approach to evaluating reversible competitive antagonists has been used in estimating the dissociation constant (apparent KB) for (+/-)-sotalol at beta adrenergic receptors which mediate a positive chronotropic response in rat atria. Cumulative dose-response curves to the beta agonists (-)-isoproterenol and (-) soterenol were obtained after mixing each agonist with (+/-)-sotalol at fixed ratios (Q = [antagonist]/[agonist]). Experimental and theoretical dose-response curves obtained with the dynamic approach were in good agreement and the lowered maximum responses to the agonist-antagonist mixtures were dependent on Q. Also, apparent KB values for (+/-)-sotalol determined by three methods were independent of Q and agonist employed in the experiment. Apparent KB values for (+/-)-sotalol obtained by the dynamic method (6 x 10(-7)-2 x 10(-6) M) were similar to those obtained by the traditional equilibrium or static approach. As judged by the similarity of the apparent KB values derived by the two independent theoretical models, the dynamic approach may be considered an effective and alternative means to evaluate reversible competitive antagonists. PMID- 6257890 TI - Possible involvement of adenine nucleotides in sympathetic neuroeffector mechanisms of dog basilar artery. AB - The transmission mechanism of sympathetic neuroeffector was studied in the isolated dog basilar artery. Electrical transmural stimulation produced an initial contractile response which was followed by a transient relaxation or a late contraction, or both relaxation and contraction. These arteries showed a marked uptake of [3H]norepinephrine ([3H]NE) or [3H]adenosine after incubation with these compounds, and electrical stimulation increased the release of [3H]NE or 3H-purine compounds. After treatment with tetrodotoxin or bretylium or in the sympathetically denervated arteries, the mechanical response to electrical stimulation and the release of 3H-compounds were attenuated; however, the mechanical response was not affected by treatment with reserpine. These results suggest that transmural stimulation releases not only [3H]NE but also 3H-purine compounds predominantly from the sympathetic nerve terminals and produces sympathetic contractile and relaxing responses. Phentolamine enhanced these sympathetic responses and augmented the release of [3H]NE and 3H-purine compounds. Exogenously applied NE produced a slowly developing contractile response and inhibited the release of 3H-purine compounds upon electrical transmural stimulation. Exogenously applied ATP produced responses which were similar in pattern to the sympathetic response and the release of [3H]NE was inhibited. Other adenine nucleotides and adenosine produced only relaxation. Theophylline attenuated the relaxing response to sympathetic nerve stimulation or to exogenously applied nucleotides. These results suggest that ATP or related nucleotides are released, concomitant with NE, from the sympathetic nerve terminals in the dog basilar artery and may act as neurotransmitters and/or modulators on presynaptic and postsynaptic membranes. PMID- 6257891 TI - Changes in beta adrenergic receptors in submaxillary glands of chronically reserpine- or isoproterenol-treated rats. AB - Submaxillary glands of rats, chronically treated with isoproterenol or reserpine undergo morphological and functional alterations. These changes have been described to resemble those seen in human cystic fibrosis. Since it has been proposed that the beta adrenergic-mediated response is altered in exocrine glands of cystic fibrosis patients, we have examined whether the drug-induced alterations in rat salivary glands were accompanied by changes in the numbers and affinities of beta adrenergic receptor sites. Beta receptor characteristics were determined by means of direct binding studies with the beta adrenergic antagonist [3H]dihydroalprenolol. Compared to controls, specific binding capacities of [3H]dihydroalprenolol per unit of protein increased by 110 +/- 14% after reserpine treatment and decreased by 34 +/- 11% after isoproterenol administration (P less than .001). The difference in the number of receptor sites remained statistically significant whether expressed per gram of fresh weight or per unit of the membrane marker 5'-nucleotidase activity. Dissociation constants of the binding were not significantly different between the treatment groups. The observed changes in the number of beta receptors showed an inverse relationship to the drug-induced presumed changes of catecholamine concentrations at the receptor sites. This suggests the existence of a feedback system which maintains the balance within the autonomous nervous system. We speculate that in cystic fibrosis this adaptive system is genetically abnormal. PMID- 6257892 TI - Multiple benzodiazepine receptor localization by light microscopic radiohistochemistry. AB - Benzodiazepine receptor binding studies have been reported suggesting the existence of at least two different benzodiazepine receptors. One distinguishing feature of these two sites is that one has a high affinity for triazolopyridazines, whereas the other has a low affinity. In this study, the regional localization of the two different receptors was examined by light microscopic radiohistochemical methods. [3H]Flunitrazepam was used to label all types of benzodiazepine receptors in slide-mounted tissue sections. CL218,872, a typical triazolopyridazine, was used to preferentially displace [3H]flunitrazepam from the subclass of receptors having a high affinity for CL218,872. Autoradiographs clearly showed that receptor binding in some regions was substantially affected by CL218,872 while that in other regions was affected to a lesser degree. Areas with receptors with high affinity for the triazolopyridazine (Type 1 receptors) included the cerebellum, globus pallidus and parts of the cerebral cortex. Areas with receptors having low affinity for the drugs (Type 2 receptors) included the superficial layer of the superior colliculus, the caudate putamen and parts of the dentate gyrus. The results of this study may help explain the physiological differences between the benzodiazepine and triazolopyridazine drugs and should point out target sites in the brain for additional studies of the apparently two different receptors. PMID- 6257893 TI - Dual mode of junctional transmission at synapses between single primary afferent fibres and motoneurones in the amphibian. AB - 1. The isolated hemisected frog spinal cord has been used to examine the effects of changes in ionic composition of perfusing medium on the intracellularly recorded e.p.s.p.s produced in single motoneurones by direct stimulation of individual dorsal root fibres through a separate intracellular micro-electrode.2. The monosynaptic single-fibre e.p.s.p.s usually reveal two distinct components, early and late. The early component is resistant to replacement of external Ca(2+) by Mn(2+) whereas the later is reversibly abolished. It is concluded that the junction between primary afferent fibre and motoneurone provides joint electrical and chemical transmission.3. The average amplitude of the unitary electrical e.p.s.p. varies at different junctions from 25 to 430 muV, mean 124 +/ 17 muV (n = 50). It is relatively stable and changes its amplitude only with changes in the height of presynaptic spike. The individual amplitudes observed in a given cell usually have a normal distribution suggesting that any variability in electrical response is entirely due to noise.4. The average amplitude of the single-fibre chemically mediated e.p.s.p. varies from less than 20 muV to 1.7 mV, mean 222 +/- 33 muV (n = 71). A positive correlation was found between the amplitudes of chemical and electrical e.p.s.p.s recorded from different motoneurones.5. Chemical e.p.s.p.s evoked by consecutive impulses in a single presynaptic fibre show statistical fluctuations in amplitude. The fluctuations occur in quantal steps in a manner described by binomial or Poisson statistics. Only in a few cases the deviation from stochastic distribution can be attributed to variable invasion of nerve impulses into the terminal region.6. The amplitude of the unit e.p.s.p. varies between 33 and 104 muV, mean 66.4 +/- 4.3 muV (n = 19). The mean quantum content (m) varies from less than 1 to more than 10. The m is reversibly reduced by Ca(2+) lack and by Mn(2+) until the chemically mediated response fluctuates according to a Poisson distribution with the unit e.p.s.p. equivalent to the single quantum of transmitter.7. When paired or repetitive stimuli are applied to the presynaptic fibre the facilitation of the chemically mediated unitary e.p.s.p. can be observed as well as the post-tetanic potentiation. The amplitude of the electrical e.p.s.p. remains unchanged during the period of post-tetanic potentiation, suggesting that the latter is attributable to some change restricted to the specific presynaptic mechanism responsible for the transmitter release but not to changes in presynaptic spike height. PMID- 6257894 TI - Calcium-mediated inactivation of calcium current in Paramecium. AB - 1. The Ca current seen in response to depolarization was investigated in Paramecium caudatum under voltage clamp. Inactivation of the current was measured with the double pulse method; a fixed test pulse of an amplitude sufficient to evoke maximal inward current was preceded by a conditioning pulse of variable amplitude (0-120 mV).2. The amplitude of the current recorded during the test pulse was related to the potential of the conditioning pulse. Reduction of test pulse current was taken as an index of Ca current inactivation. The current recorded during a test pulse showed a progressive decrease to a minimum as the potential of the conditioning pulse approached +10 to +30 mV. Further increase in conditioning pulse amplitude was accompanied by a progressive restoration of the test pulse current. Conditioning pulses near the calcium equilibrium potential had only a slight inactivating effect on the test pulse current.3. Injection of a mixture of Cs and TEA which blocked late outward current had essentially no effect on the inward current or its inactivation.4. Elevation of external Ca from 0.5 to 5 mM was accompanied by increased inactivation of the test pulse current. The enhanced inactivation of the test pulse current was approximately proportional to the increase in current recorded during the conditioning pulse.5. Following injection of the Ca chelating agent, EGTA, the inactivation of the test pulse current was diminished; in addition, the transient inward current relaxed slightly more slowly, and the transient was followed by a steady net inward current.6. The time course of recovery from inactivation in the double pulse experiment approximated a single exponential having a time constant of 80-110 msec. Injection of EGTA shortened the time constant by as much as 50%.7. It is concluded that interference with the entry of Ca or enhanced removal of intracellular free Ca(2+) interferes with the process of Ca current inactivation, while enhanced entry of Ca promotes the process of inactivation. While the mechanism of inactivation is unknown, arguments are presented that the accumulation of intracellular Ca influences the Ca channel conductance. PMID- 6257895 TI - Distribution and pharmacological properties of synaptic and extrasynaptic glutamate receptors on crayfish muscle. AB - 1. The distribution of glutamate sensitivity was measured in the opener muscle in the walking legs of the crayfish (Cambarus clarkii). L-Glutamate was ionophoretically applied under visual control. 2. Bundles of a few muscle fibres were isolated and viewed with Nomarski optics. Two axons, presumably excitatory and inhibitory, branched widely over the surface of individual muscle fibres, forming numerous clusters of boutons or varicosities. 3. Glutamate sensitivity was measured from the slope of the dose-response curves obtained by ionophoretic application of L-glutamate and expressed as mV/nC. The highest sensitivities were about 100 mV/nC, obtained at the edge of synaptic boutons. The sensitivity declined to less than 5% about 2 micrometer away from the synaptic terminal. The time course of glutamate potentials was approximately the same as that of spontaneous synaptic potentials. 4. Glutamate depolarization started within 300 microsec after ionophoretic release of glutamate. This time lag was shorter than the synaptic delay of the nerve-evoked synaptic potential measured with an extracellular micro-electrode. This indicates that glutamate depolarization results from a direct action on the post-synaptic receptor. 5. Application of L alpha-kainic acid decreased the amplitude of the glutamate potential produced at the synaptic region, whereas kainate increased the amplitude of the glutamate potential at the extrasynaptic region. It is suggested that the pharmacological properties of the extrasynaptic receptor differ from those of the synaptic receptor. Possible mechanisms for the different actions of kainate are discussed. PMID- 6257896 TI - Quinacrine (mepacrine) action at frog end-plate. AB - 1. The effects of quinacrine on end-plate currents (e.p.c.s.), miniature end plate currents (m.e.p.c.s.) and ionophoretic responses at voltage clamped frog end-plates were investigated. 2. A quinacrine concentration (2 microM) that by itself has little effect on m.p.e.c.s. will considerably attenuate responses to bath applied carbachol. The combined effect of the two drugs causes the m.e.p.c.s. to disappear. 3. The depressant effect of quinacrine on ionophoretic responses to carbachol or acetylcholine is increased in acid solutions and decreased in alkaline solutions, suggesting that quinacrine is active as an acridinium ion. 4. Quinacrine (2-10 microM) causes a use-dependent block of end plate channels which manifests as an inhibitory effect of an ionophoretic prepulse on the response to a test pulse. The inhibitory interaction decays exponentially with a time constant tau s that depends on the nature of the agonist used for the prepulse, on the quinacrine concentration, and on the membrane potential. 5. Quinacrine (5-20 microM) reduces the amplitude of e.p.c.s. and m.e.p.c.s. It also increases the rate of decay of the e.p.c. or m.e.p.c. tails, which remain exponential. The decay rate constant 1/tau f increases linearly with quinacrine concentration both in the presence and absence of 3 microM-neostigmine. The slope of this linear relation increases slightly with membrane hyperpolarization. 6. These data suggest that quinacrine's main action is a slow, voltage dependent blockade of open end-plate channels, though there are probably additional effects on acetylcholinesterase and channel opening. In accordance with the open channel blocking model, 1/tau s and 1/tau f both increase linearly with quinacrine concentration. However, the slopes of these lines lead to rather different estimates of the forward blocking rate constant (8 X 10(7) and 4 X 10(8) M-1 S-1 respectively). 7. The unblocking rate constant is about 5 S-1 at -80 mV. It is much more voltage dependent than the forward rate constant. PMID- 6257897 TI - End-plate channel opening and the kinetics of quinacrine (mepacrine) block. AB - 1. The effects of quinacrine on the relaxation of the agonist-induced currents in response to a voltage step were investigated at voltage clamped frog end-plates. A fast perfusion technique allowed the application of known concentrations of the agonist acetylcholine (ACh) or carbachol to end-plate viewed with Nomarski optics. 2. In the presence of quinacrine, and in response to a hyperpolarizing voltage jump, an agonist-induced current shows a fast initial relaxational increase and then relaxes slowly back to a new equilibrium level. 3. The slow relaxation can be described by a single exponential with a time constant tau s . tau s gets smaller at increasing quinacrine concentrations (0--2 microM) and the decay rate constant, 1/tau s, increases linearly with quinacrine concentration. Increasing agonist concentration reduces tau s, in a manner dependent on the nature of the agonist. Tau s is markedly lengthened at more hyperpolarized potential, but this voltage effect gets less at higher concentrations of agonist. 4. These data suggest a slow voltage dependent blockage of open end-plate channels by quinacrine. The binding rate constant of quinacrine is estimated as 10(8) M-1 s-1, and the voltage dependent, backward rate constant, as 5 s-1 at -60 mV and 1 s-1 at -140 mV. These values are in fair agreement with those obtained from the analysis presented in the preceding paper. 5. The agonist concentration dependence of the blocking kinetics is compatible with a simple model for channel opening. In this model, independent sequential binding of two agonist molecules leads to an isomerization of the receptor. The intrinsic binding constant of ACh is estimated to be around 20 microM, and for carbachol around 200 microM. Distinct isomerization constants could lead to a maximal activation of 70% of the available channels by ACh, and only 40% by carbachol. 6. An example of a possible interaction in between quinacrine block and desensitization is shown. At the break of an hyperpolarizing jump which has increased quinacrine blockade, a transient increase in the synaptic current is observed with apparently a temporary reduction of the desensitization. PMID- 6257900 TI - Widows and widowers and their medication use: nursing implications. PMID- 6257899 TI - Effects of strontium ions on end-plate channel properties. AB - 1. Changes in end-plate channel properties resulting from substitution of Sr2+ for Ca2+ in the Ringer solution have been analysed at the voltage clamped frog end-plate, by recording m.e.p.c.s and ACh induced noise variance. 2. In 2 mM-Sr2+ -Ringer the peak size of m.e.p.c.s showed a very small increase, and the time constant of the decay phase (tau m.e.p.c.), at any given voltage, was increased by a factor of about two compared to control Ringer. The voltage dependence of tau m.e.p.c. was the same in both solutions. 3. Addition of increasing amounts of CaCl2 to 2 mM-Sr2+--Ringer produced a progressive shortening of tau m.e.p.c., with no change in voltage dependence. 4. Estimates of single channel properties from noise analysis showed that the elementary conductance appeared to be slightly increased in 2 mM-Sr2+--Ringer, whilst the mean channel life-time was prolonged by a factor of about two. These changes in single channel properties are sufficient to account for the observed changes in m.e.p.c.s. 5. Following inhibition of cholinesterase activity by neostigmine, similar effects on m.e.p.c.s and single channel properties were still observed on changing to 2 mM Sr2+--Ringer. The shapes of m.e.p.c.s in Sr2+ + neostigmine Ringer were often altered, and showed flat 'plateaus'. 6. The observed effects of Sr2+--Ringer on channel life-time cannot be explained on the basis of changes in surface charge density on the membrane, and suggest that divalent cations have an additional, and more direct, influence on receptor channel properties. PMID- 6257898 TI - Voltage-clamp experiments in normal and denervated mammalian skeletal muscle fibres. AB - 1. The vaseline-gap voltage-clamp method has been applied to the study of ionic currents in cut pieces from innervated and 5--7 days denervated rat skeletal muscle fibres. 2. Kinetic analysis of sodium currents in innervated rat muscle showed them to be similar to those in frog muscle, except that rat sodium channels are activated at slightly more negative potentials. Peak sodium conductances of 40--50 m-mho/cm2 were measured, corresponding to values of GNa of 100--120 m-mho/cm2. 3. The permeability sequence of the sodium channel to several organic and inorganic cations is Li+ greater than Na+ greater than hydroxylammonium greater than hydrazinium greater than guanidinium approximately ammonium greater than K+. TMA+ and Ca2+ were not measurably permeant. 4. Denervation appears to shift activation and inactivation parameters of sodium currents by approximately 10 mV to more negative potentials, but does not appreciably affect the maximum peak sodium conductance or the time constants for activation and inactivation. 5. Dose--response curves for block by tetrodotoxin in innervated fibres are fitted well by assuming binding of toxin to a single population of channels with a dissociation constant of about 5 nM. In denervated fibres there appears in addition a second population of channels with a dissociation constant in the micromolar range. These relatively toxin-insensitive channels respond less rapidly to potential changes, and can contribute up to 25- 30% of the total sodium conductance. 6. The potassium currents of innervated rat muscle were similar to those of frog muscle in their voltage dependence of activation. 7. The time constant for inactivation of the sodium current, tau h, at -13 mV showed a temperature dependence measured between 10 and 20 degrees C equivalent to an average Q10 of 2 . 3. The Q10 for the time constant of activation of the potassium current tau n, averaged 2 . 5 between -40 mV and +40 mV, measured over the same temperature range. PMID- 6257901 TI - Interface of psychiatric clinical specialists in a community hospital setting. AB - In the beginning a question was posed, "Is clinical specialization an effective nursing role in the general hospital setting? In conclusion, we believe that the experience has shown it is, when certain factors are operating. These factors are a supportive nursing administration coupled with our collaborative efforts. The most significant of these changes has been strengthening nursing identity through peer support and the nurse-to-nurse consultation process. PMID- 6257902 TI - Nursing theory and the assessment of families. PMID- 6257903 TI - Obsessive-compulsive behavior: an overview of four psychological frameworks. AB - Four frameworks for understanding obsessive-compulsive behavior have been presented. It is apparent that there is no single, simple basis for obsessive compulsive symptomatology. Obsessions and compulsions are manifestations of different psychological processes and may exist in conjunction with many types of mental illness in addition to those presented. With increased knowledge about the dynamics of obsessions and compulsions, the mental health professional will achieve a greater understanding of the client who expresses himself through these symptoms. PMID- 6257904 TI - The Health Opinion Survey translated into Spanish as a measure of stress for Hispanic cultures. PMID- 6257905 TI - Cells, enzymes and interstitial lung disease. The Philip Ellman Lecture. PMID- 6257906 TI - The IgM and IgG response to Bordetella pertussis vaccination and infection. AB - Ultracentrifugation was used to separate IgG from IgM in serum samples from children after pertussis vaccination or infection and the fractions were examined by indirect haemagglutination (IHA) and complement-fixation (CF) tests. IHA detected pertussis-specific IgM and IgG but CF detected only IgG which appeared to be of a different subclass from the IHA IgG. The IgM titres were higher after infection than after vaccination but the reverse tended to apply to the IgG titres. Little IgM or CF IgG was detected 5 months after a dose of vaccine, but the IHA IgG persisted longer. Vaccinated children who were subsequently infected showed IgM and CF IgG responses similar to those of unvaccinated, infected children but the IHA IgG titres reached much higher levels. PMID- 6257907 TI - Identification of Leptospira serovars by restriction-endonuclease analysis. AB - Strains of Leptospira interrogans were examined by restriction-endonuclease analysis. Serovars hardjo and balcanica gave patterns that differed from each other, and from those of other members of the Hebdomadis serogroup and members of other serogroups. The method should be useful for the identification of leptospires and might throw light on problems of their classification. PMID- 6257908 TI - Detailed transcription map of the extrachromosomal ribosomal RNA genes in Tetrahymena thermophila. PMID- 6257909 TI - Sequence definition and organization of a human repeated DNA. PMID- 6257910 TI - Efficient catalysis of polycytidylic acid-directed oligoguanylate formation by Pb2+. PMID- 6257911 TI - Estimation of phosphofructokinase activity in homogenates of rat heart using a new isotopic assay at low substrate concentration. PMID- 6257912 TI - Cardiac calmodulin and its role in the regulation of metabolism and contraction. PMID- 6257913 TI - Effect of phosphodiesterase inhibitors on heart contractile behaviour, protein kinase activity and cyclic nucleotide levels. PMID- 6257914 TI - Interaction between parathyroid hormone and the beta-adrenoceptor system in cultured rat myocardial cells. PMID- 6257915 TI - Myoglobin and cytochrome oxidase in the myocardium of the developing chick. PMID- 6257916 TI - The beneficial effect of a calcium channel blocker, Diltiazem, on the ischemic reperfused heart. PMID- 6257917 TI - Psychoneuroendocrinology, biorhythms, and Chinese medicine. AB - The discovery of an endogenously formed opioid substance in the body which is intimately related to corticotrophin and, thus, a major consideration in the body's response to stress already has demonstrated the impact that psychoneuroendocrinology can have on the practice of medicine. The psychoneuroendocrinologic system is characterized by a daily rhythm; because of this rhythmic variation, the body is in different physiologic states at different times of the day. This has raised some important questions for clinical practice. Western medical science and Chinese medicine are compared and suggestions are made on how to best utilize the knowledge currently being gained in psychoneuroendocrinology and biorhythms. PMID- 6257918 TI - Comparison of the nucleotide sequence at the 5' end of RNAs from nine aphthoviruses, including representatives of the Seven serotypes. AB - The sequence of about 70 nucleotides at the 5' end of the RNAs of nine different aphthoviruses (foot-and-mouth disease viruses), including representatives of the seven serotypes of the virus, has been determined by partial enzyme digestion of (32)P-end-labeled S fragment-that part of the RNA lying to the 5' side of the poly(C) tract and including the 5' end of the molecule. The S fragments were prepared from polyadenylated virus-specific RNA extracted from infected cells by digestion with RNase H in the presence of oligo(dG)(12-18). The first 27 nucleotides from the 5' end were highly conserved in all the RNAs. This region was followed by a more variable region of about 15 nucleotides, showing some length and sequence heterogeneity and including potential but probably nonutilized initiation codons. In agreement with previous homology studies, the sequencing results showed that the European serotypes A, O, and C form a group distinct from the SAT serotypes and that the Asia 1 serotype is closely related to the European group. The lengths of the S fragments of two different RNAs were confirmed as containing 360 to 400 nucleotides by gel electrophoresis with reference to nucleotide markers of known size. PMID- 6257919 TI - Avian erythroblastosis virus produces two mRNA's. AB - We analyzed the viral mRNA's present in fibroblast nonproducer clones transformed by avian erythroblastosis virus. Two size classes of mRNA (28 to 30S and 22 to 24S) were identified by solution hybridization with both complementary DNA strong stop and complementary DNA made against the unique sequences of avian erythroblastosis virus. Based upon the kinetics of hybridization with complementary DNA made against the unique sequences of avian erythroblastosis virus, we estimated that there were 400 to 500 copies of the 28 to 30S RNA per cell and 200 to 250 copies of the 22 to 24S RNA per cell. Both RNA species were packaged in the virion. In vitro translation of the 28 to 30S virion RNA yielded a 75,000-dalton protein which was the 75,000-dalton gag-related polyprotein found in avian erythroblastosis virus-transformed cells. In vitro translation of the 22 to 24S virion RNA yielded two proteins (46,000 and 48,000 daltons). This indicates that there may be two genes in avian erythroblastosis virus, one coding for the 75,000-dalton gag-related polyprotein and the second coding for the 46,000- or 48,000-dalton protein or both. PMID- 6257920 TI - Integration, expression, and infectivity of exogenously acquired proviruses of Rous-associated virus-O. AB - We investigated the integration sites, infectivities, and expression of Rous associated virus-0 (Rav-0) DNAs in exogenously infected turkey and chicken cells. Restriction endonuclease analyses of the DNAs of RAV-0-infected cells indicated that unique integration sites of RAV-0 DNA were detectable in clones of RAV-0 infected cells but not in mass-infected cell cultures. In addition, the sites of integration of RAV-0 DNA differed in each of the seven clones of RAV-0-infected cells examined. Thus, endogenous RAV-0 proviruses appeared to integrate at multiple sites in cellular DNA, which were distinct from the sites of integration of endogenous RAV-0 genomes. Since exogenous RAV-0 proviruses are expressed at 10(3)- to 10(4)-fold-higher levels and are 10(3)- to 10(4)-fold more infectious in transfection assays than the endogenous RAV-0 genome of uninfected V+ chicken cells, these results are consistent with the hypothesis that transcription of the endogenous RAV-0 genome is regulated by flanking cellular DNA sequences. Although all RAV-0-infected cells contained infectious RAV-0 DNA and produced high titers of RAV-0 compared with uninfected V+ cells, different clones of RAV-0 infected chicken cells differed by as much as 30-fold in their levels of virus production. The infectivity of the DNA of each clone of RAV-0-infected cells correlated with the amount of virus produced by that clone. However, these differences did not appear to be correlated either with the number of exogenous RAV-0 proviruses in different clones or with the infectivity of RAV-0 produced by different clones, indicating that differences either in modification of RAV-0 DNAs or in the cellular sequences flanking exogenous RAV-0 DNAs were responsible for the observed differences in expression and infectivity. PMID- 6257921 TI - Simian virus 40-associated small RNA: mapping on the simian virus 40 genome and characterization of its synthesis. AB - The simian virus 40 (SV40)-associated small RNA (SAS-RNA) has previously been shown to arise late in SV40 lytic infection and to bear homology with the SV40 early mRNA's, or the SV40 genome, at map position 0.21. By using hybridization analysis, we determined that the SAS-RNA is between 62 and 65 nucleotides in length and its homology region lies between nucleotides 2760 and 2825 of the SV40 late(+) DNA strand. Viable deletion mutants which lacked part or all of this region made no SAS-RNA, strongly indicating that this is the coding region of the SAS-RNA. The expected sequence for the SAS-RNA, determined from the DNA sequence between nucleotides 2760 and 2825, appeared to be very pyrimidine rich (76% uridine and cytidine). Deletion or alteration of sequences immediately preceding the SAS-RNA coding region (approximately nucleotides 2716 to 2748) resulted in the loss of SAS-RNA production. These sequences may be part of a promotor for SAS RNA synthesis or a processing site for its excision from long nuclear late transcripts. Under growth conditions where late transcription was not fully initiated (tsA58 at 41 degrees C; wild-type SV40 in the presence of 1-beta-D arabinofuranosylcytosine), no SAS-RNA was produced, indicating that the expression of the SAS-RNA is regulated by a mechanism related to the control of late transcription. PMID- 6257922 TI - Physical map of infectious baboon type C viral DNA and sites of integration in infected cells. AB - Three species of unintegrated viral DNAs were found in permissive cells infected with baboon type C virus. The major species was a 9.0-kilobase (kb) linear DNA that was infectious. A restriction endonuclease map of this DNA was constructed and oriented with respect to the viral RNA. The linear DNA had a 0.6-kb sequence repeated at each terminus. These terminal repeat sequences were required for infectivity of the viral DNA. The minor species of the unintegrated viral DNAs were covalently closed circles of 9.0 and 8.4 kb. The smaller circle was in two- to threefold excess over the larger circle. The difference appeared to be that the smaller circle lacked one of the two 0.6-kb repeat sequences found in the larger circle. Restriction endonuclease maps of the integrated viral DNAs were constructed, and the sequences on both viral DNA and cellular DNA that are involved in integration were determined. The integrated viral DNA map was identical to that of the unintegrated infectious 9.0-kb linear DNA. Therefore, a specific site in the terminal repeat sequence of the viral DNA was used to integrate with the host cell DNA. The sizes of the cellular DNA fragments were different from clone to clone but stable with cell passage. Therefore, many sites in the cell DNA can recombine with the viral DNA. PMID- 6257923 TI - Translational control of protein synthesis after infection by vesicular stomatitis virus. AB - Four hours after infection of BHK cells by vesicular stomatitis virus (VSV), the rate of total protein synthesis was about 65% that of uninfected cells and synthesis of the 12 to 15 predominant cellular polypeptides was reduced to a level about 25% that of control cells. As determined by in vitro translation of isolated RNA and both one- and two-dimensional gel analyses of the products, all predominant cellular mRNA's remained intact and translatable after infection. The total amount of translatable mRNA per cell increased about threefold after infection; this additional mRNA directed synthesis of the five VSV structural proteins. To determine the subcellular localization of cellular and viral mRNA before and after infection, RNA from various sizes of polysomes and nonpolysomal ribonucleoproteins (RNPs) was isolated from infected and noninfected cells and translated in vitro. Over 80% of most predominant species of cellular mRNA was bound to polysomes in control cells, and over 60% was bound in infected cells. Only 2 of the 12 predominant species of translatable cellular mRNA's were localized to the RNP fraction, both in infected and in uninfected cells. The average size of polysomes translating individual cellular mRNA's was reduced about two- to threefold after infection. For example, in uninfected cells, actin (molecular weight 42,000) mRNA was found predominantly on polysomes with 12 ribosomes; after infection it was found on polysomes with five ribosomes, the same size of polysomes that were translating VSV N (molecular weight 52,000) and M (molecular weight 35,000) mRNA. We conclude that the inhibition of cellular protein synthesis after VSV infection is due, in large measure, to competition for ribosomes by a large excess of viral mRNA. The efficiency of initiation of translation on cellular and viral mRNA's is about the same in infected cells; cellular ribosomes are simply distributed among more mRNA's than are present in growing cells. About 20 to 30% of each of the predominant cellular and viral mRNA's were present in RNP particles in infected cells and were presumably inactive in protein synthesis. There was no preferential sequestration of cellular or viral mRNA's in RNPs after infection. PMID- 6257924 TI - Characterization of endogenous and exogenous mouse mammary tumor virus proviral DNA with site-specific molecular clones. AB - Restriction fragments of the mouse mammary tumor virus (MMTV) proviral DNA were obtained by molecular cloning procedures. A 4-kilobase fragment delimited by two PstI sites was isolated from unintegrated, linear MMTV DNA and amplified in the pBr322 plasmid vector. EcoRI fragments of proviral DNA, integrated into the genome of a GR mammary tumor cell line, were isolated as lambda recombinant molecules. Five different recombinant phages which contained the 3' region of the MMTV proviral DNA and adjacent host DNA sequences were isolated. Heteroduplex analysis and S1 nuclease digestion suggested that there is no extensive sequence homology in the host DNA flanking the different proviral genes. The cloned DNA was fractionated into site-specific restriction fragments which served as molecular probes in the analysis of the endogenous MMTV proviral copies of C3H, GR, BALB/c, and feral mice. This allowed the correlation of MMTV-specific EcoRI fragments obtained from genomic DNA of these strains with the 5' and 3' ends of the proviral gene. Restriction fragments of two clones which contained the proviral sequences adjacent to the flanking host DNA as well as 1 to 2 kilobases of host DNA were used as hybridization probes, and the results allow the following conclusions: the proviral DNA of both clones contains nucleotide sequences complementary to the 5' and 3' ends of proviral DNA; and the host DNA flanking one clone belongs to the unique class of genomic DNA, whereas the DNA flanking the second clone is reiterated at least 15 times within the mouse genome. PMID- 6257925 TI - RNA synthesis of vesicular stomatitis virus. X. Transcription and replication by defective interfering particles. AB - In cells coinfected by standard vesicular stomatitis virus (VSV) and defective interfering (DI) T particles, small RNA consisting of 46 nucleotides was synthesized in molar excess over other VSV-specific RNAs. Although its rate of synthesis increased over time, small RNA accumulated linearly, suggesting that the molecule is unstable. In contrast, replication of the genome RNA of DI T particles was relatively constant after 3 h of infection, resulting in the intracellular accumulation of stable genomic and antigenomic RNA of DI T particles. Coinfection of cells with DI T particles and selected temperature sensitive mutants from all five complementation groups of VSV indicated that the replication of DI genomes was controlled separately from the synthesis of small RNA. Also, when viral RNA replication was inhibited by cycloheximide, small RNA continued to be synthesized as long as there were enough templates present. These results indicate that small RNA is synthesized by the enzyme(s) involved in VSV transcription and that its dependence on RNA replication is due to the requirement for template amplification. PMID- 6257926 TI - Abelson murine leukemia virus mutants deficient in kinase activity and lymphoid cell transformation. AB - Abelson murine leukemia virus transforms both lymphoid cells and fibroblasts in vitro and induces a unique type of thymus-dependent lymphoma in vivo. Four fibroblast-transforming strains of Abelson murine leukemia virus were identified, based on the sizes of the Abelson murine leukemia virus-specific phosphoproteins produced by these isolates. Two of these strains, the standard P120- and the P160 producing viruses, transformed lymphoid cells efficiently in vitro and induced Abelson disease in vivo. Two other strains, which synthesized small Abelson murine leukemia virus-specific proteins with molecular weights of 90,000 (P90) and 100,000 (P100), transformed lymphoid cells very poorly both in vitro and in vivo. The reduced oncogenic potentials of these isolates were correlated with a high level of synthesis of fairly unstable P90 and P100. In addition, neither P90 nor P100 functional efficiently in protein kinase assays. The correlation of abnormal metabolism and deficient protein kinase activity with the reduced oncogenic potentials of these virus strains supported a direct role for these proteins and the kinase activity in transformation. Furthermore, these results suggested that the requirements for lymphoid cell transformation and fibroblast transformation are different. PMID- 6257927 TI - Replicative RNA synthesis and nucleocapsid assembly in vesicular stomatitis virus infected permeable cells. AB - A permeable-cell system has been developed to study the replication of vesicular stomatitis virus. When vesicular stomatitis virus-infected BHK cells were permeabilized by lysolecithin treatment, they incorporated nucleoside triphosphates into RNA and amino acids into proteins at nearly normal rates. The viral mRNA's synthesized appeared normal in polarity, size distribution, and polyadenylation, and all five viral proteins were synthesized. Replication of the viral genome proceeded, and full-length RNA strands were synthesized in amounts and polarities resembling those found in intact cells. These full-length RNAs associated with viral N proteins to form RNase-resistant nucleocapsids of normal buoyant density. Permeable cells appear to represent ideal hosts for studying vesicular stomatitis virus replication since they closely mimic in vivo conditions while retaining much of the experimental flexibility of current in vitro systems. PMID- 6257928 TI - Association of pp60src and src protein kinase activity with the plasma membrane of nonpermissive and permissive avian sarcoma virus-infected cells. AB - The intracellular localization of pp60src and src protein kinase activity in avian sarcoma virus (ASV)-infected chicken embryo fibroblasts and transformed and morphologically reverted field vole cells was examined by subcellular fractionation procedures. Fractionation by differential centrifugation of Dounce homogenized cellular extracts prepared from vole cells showed that 83 to 91% of pp60src sedimented with particulate subcellular components from both transformed and revertant vole cells. A slightly lesser amount (60 to 70%) of pp60src was found associated with the particulate fraction from ASV-infected chicken embryo fibroblasts. The distribution of src protein kinase activity in the cytosol and particulate cell fractions was identical to that of pp60src, indicating no detectable differences in the activity of cytosol- and particulate-associated pp60src. When subcellular components of the cell were fractionated by discontinuous sucrose gradient centrifugation, similar amounts of both pp60src and src protein kinase activity cosedimented with the plasma membrane fractions from both transformed and revertant vole cells, as well as from ASV-infected chicken embryo fibroblasts. src protein kinase activity associated with plasma membrane fractions prepared from vole cells and ASV-infected chicken embryo fibroblasts was resistant to extraction with high salt concentrations, but partial elution was achieved with nonionic detergent. Thus, in both transformed and morphologically reverted vole cells, pp60src is intimately associated with the plasma membrane. Since transforming virus can be rescued from revertant vole cells by fusion to chicken embryo fibroblasts, revertant vole cell pp60src is capable of inducing morphological transformation. Thus, although the data presented herein suggest that transformation requires the association of pp60src with the plasma membrane, the binding of pp60src to the plasma membrane per se is insufficient to induce morphological transformation and requires the additional interaction with a specific target membrane protein which appears to be defective in revertant vole cells. PMID- 6257930 TI - Structure of and alterations to defective murine sarcoma virus particles lacking envelope proteins and core polyprotein cleavage. AB - HTG2 hamster cells produce a defective murine sarcoma virus lacking gp70 and, consequently, viral surface projections (knobs), but the lack of knobs appears to have no effect on intramembrane particle distribution. In addition, it has been noted that the core of the virus remains in the "immature" form as a result of the failure of the polyprotein precursor (p65) to undergo cleavage. However, incubation of HTG2 virus with avian myoblastosis virus was found to yield specific cleavage products of p65. PMID- 6257929 TI - Analysis of herpes simplex virus nucleoprotein complexes extracted from infected cells. AB - HEp-2 cells were infected with herpes simplex virus type 1 and labeled with [3H]thymidine and 14C-amino acids. Infected cells or nuclei prepared from them were extracted with Triton X-100 and NaCl, utilizing a method recently described, and the low-speed supernatant (extract) was partially purified by sedimentation on sucrose gradients. A nucleoprotein complex which sedimented as a wide peak around 200S was identified. The nucleoprotein complex contained viral DNA, which banded at the expected density in CsCl isopycnic gradients and was intact after measurements taken on electron microscopic photographic enlargements. The autoradiographic pattern of 14C-labeled proteins after electrophoresis showed that only a few of the virus-specific polypeptides were present in the nucleoprotein complexes, in particular, VP5, VP12, VP15.2, VP19, and VP24. Cellular histones were absent. The extracts and the nucleoprotein complexes were centrifuged to equilibrium in metrizamide density gradients without prefixation. Electron microscopic direct visualization of the nucleoprotein complexes after sucrose or metrizamide purification revealed that the proteins were preferentially associated with one end of the DNA molecule and formed large irregular terminal thickenings or capsid-like transparent shells enclosing polyglobular cores. No nucleosomes were observed on herpes simplex virus nucleoprotein complexes. The same type of complex was detected after phosphonoacetic acid addition, and grossly altered nucleocapsids were formed. PMID- 6257932 TI - Envelope assembly mutant of rous sarcoma virus. AB - The properties of a novel nonconditional envelope mutant of Rous sarcoma virus, rdPN3/2-SR-D, defective in the assembly of viral glycoproteins into mature virions, are described. PMID- 6257934 TI - Possible role of wild mammals in transmission of pseudorabies to swine. AB - Of 73 wild and domestic mammals tested from an area endemic for pseudorabies in swine, 16 showed natural pseudorabies virus infection, 8 from farms with no pseudorabies history. In transmission experiments with swine and raccoons (Procyon lotor), pseudorabies was not transmitted between raccoons but was transmitted reciprocally between raccoons and swine by contact and when either consumed infected carrion of the other. The fluorescent antibody tissue section test proved valuable in diagnosis of pseudorabies, especially when employed with the virus isolation test. PMID- 6257933 TI - Partial phosphorylation in vivo of the avian retrovirus pp32 DNA endonuclease. AB - Avian retrovirus pp32, a DNA endonuclease which is structurally related to the avian retrovirus DNA polymerase beta polypeptide, has been demonstrated to be partially phosphorylated in vivo. Unlabeled or [35S]methionine-labeled pp32 from avian sarcoma virus or avian myeloblastosis virus migrated as an electrophoretic doublet on discontinuous sodium dodecyl sulfate-polyacrylamide slab gels. However, pp32 immunoprecipitated from avian sarcoma virus labeled in vivo with [32P]orthophosphoric acid migrated as a single band, which co-electrophoresed with the slower-moving band of the doublet represented by unlabeled or 35S labeled pp32. The presence of a slower-migrating phosphorylated band in pp32 suggests that the observed electrophoretic heterogeneity of purified pp32 is due to partial phosphorylation. Tryptic peptide analysis of 32P-labeled avian sarcoma virus beta and pp32 demonstrated that all the three labeled peptides in the beta polypeptide were also present in pp32. However, pp32 had one tryptic peptide which was preferentially labeled in comparison to the comigrating peptide found in beta digests, suggesting that phosphorylation may play a role in the processing of pp32 from beta or in the regulation of its associated DNA endonuclease activity. PMID- 6257935 TI - Susceptibility of two turtle species to eastern equine encephalitis virus. AB - Two species of turtle collected in southern New England were inoculated subcutaneously with eastern equine encephalitis virus. The spotted turtles (Clemmys guttata) developed viremia and neutralizing antibody after exposure to 3 logs or more of virus. Viremia was not detected in the eastern painted turtles (Chrysemys picta), and neutralizing antibody was detected in only 1 of 15 inoculated C. picta; however, since pre-inoculation serum was not obtained from this animal, the possibility of natural infection cannot be eliminated. PMID- 6257931 TI - Cloned human polyomavirus JC DNA can transform human amnion cells. AB - The genome of the human polyomavirus JC (Mad-1 strain) was molecularly cloned in Escherichia coli by using the plasmid vector pBR322. Recombinant DNA molecules were constructed with the entire JC genome inserted either at its unique EcoRI site at 0.0 map units or at its unique BamHI site at 0.51 map units. Viral DNA from each of these recombinant plasmids was capable of transforming human amnion cells, and cell lines established from transformed foci were positive for JC tumor antigen as assayed by indirect immunofluorescence. PMID- 6257936 TI - Poxvirus infection of the white-tailed tropicbird (Phaethon lepturus) in Bermuda. AB - Lesions caused by an avian poxvirus were identified on the face and nares of fledgling white-tailed tropicbirds (Phaethon lepturus catesbyi) in the natural environment on Bermuda. Between 1958 and 1978, 6 of 81 fledglings found off the nest and unable to fly at departure time had lesions suggestive of poxvirus infection. More detailed nest-site surveys from 1974 to 1978 indicated an overall prevalence of less than 0.5%, involving the fledgling population only. PMID- 6257937 TI - Avian pox infection in a Canada goose (Branta canadensis). AB - Lesions suggestive of Avian Pox were found on a debilitated Canada goose (Branta canadensis). These were demonstrated histologically to be characteristic poxvirus lesions and poxvirus particles were seen using electron microscopy. The virus was successfully transmitted to domestic geese but not to leghorn chickens or to domestic ducks. PMID- 6257938 TI - Avian pox infection, aspergillosis and renal trematodiasis in a Royal tern. AB - Poxvirus infection and aspergillosis were diagnosed in a Royal tern (Thalasseus maximus) based on gross and microscopic lesions. This represents the first known report of avian pox in a tern. Renal trematodiasis, caused by a species of Renicola also is described. PMID- 6257939 TI - Injection of collagenase in the treatment of herniated lumbar disk. Initial clinical report. AB - Twenty-nine patients with persistent, low back and sciatic pain received intradiscal collagenase at a single abnormal disk space after two months of conservative therapy and two weeks of additional bed rest. Complete pain relief was achieved in six patients (21%), notable relief in 12 (42%), moderate in six (21%), and slight in one. Four patients (14%) who obtained no improvement by enzyme injection recovered after extruded disk fragments were removed from the spinal canal during a later operation. Pain relief after collagenase injection took place gradually over a two- to three-week period and was associated with some early backache. Improvement then continued at a slower rate for two to three months. There were no adverse effects of enzyme therapy. Injected disk spaces usually showed radiological narrowing. PMID- 6257940 TI - Use of IgM-hepatitis A antibody testing. Investigating a common-source, food borne outbreak. AB - An outbreak of hepatitis, type A, affecting 30 employees of a large metropolitan department store was investigated using traditional case findings, a food preference questionnaire, and case-control methods. In addition, the new serological tests for IgM and IgG antibody to hepatitis A virus (anti-HAV) were employed to establish a serological diagnosis of hepatitis A infection, to define the control group, and to identify the index case, an asymptomatic food handler. Twenty-five of 25 cases tested had IgM anti-HAV, whereas none of 73 controls and one of 46 food handlers were IgM anti-HAV positive. This test eliminated three suspect cases that were diagnosed as hepatitis but that had atypical epidemiologic features. Epidemiologic and serological analysis confirmed the association of illness with eating in the employees' cafeteria and eating cold sandwiches. PMID- 6257941 TI - Effect of warfarin on survival in small cell carcinoma of the lung. Veterans Administration Study No. 75. AB - In a controlled, randomized study, survival of patients with small cell carcinoma of the lung (SCCL) was prolonged on addition of warfarin sodium to combination chemotherapy plus radiation therapy. Median survival for 25 control patients was 24 weeks and for 25 warfarin-treated patients was 50 weeks. This difference could not be accounted for by differences between groups in performance status, extent of disease, age, or sex. The survival advantage associated with warfarin administration was observed both for patients with extensive disease and for those who failed to achieve complete or partial remission. The warfarin-treated group also demonstrated a significantly increased time to first evidence of disease progression. These results suggest that warfarin may be useful in the treatment of SCCL and also support the hypothesis that the blood coagulation mechanism may be involved in the growth and spread of cancer in man. PMID- 6257942 TI - Plasma levels of cyclic nucleotides in patients with essential hypertension. AB - We studied plasma levels of cyclic nucleotides and their responses to submaximal exercise as an endogenous adrenergic stimulation in normal subjects, untreated and treated patients with essential hypertension to assess the roles of various hormones and the autonomic nervous system in essential hypertension. Plasma c-AMP level was significantly higher in untreated, diuretic-treated patients and those treated with propranolol than in normal subjects, but plasma c-GMP level was comparable in normal subjects and untreated patients. Plasma c-AMP decreased significantly, whereas plasma c-GMP increase significantly, after chronic propranolol therapy. Plasma c-AMP increased significantly after submaximal exercise in normal subjects, untreated patients and those treated with propranolol, but plasma c-GMP increased significantly only in normal subjects. The increase in plasma c-AMP was significantly higher in untreated patients than in normal subjects and patients treated with propranolol. Moreover, the percent increase in plasma c-AMP was significantly higher in untreated patients than in those treated with propranolol. Therefore, it is suggested that the sympathetic nervous system may be hyperactive, and that a hyperreactivity of the beta adrenergic receptors may play an important role in essential hypertension. PMID- 6257943 TI - [Clinical statistics for lung neoplasms in Japan according to their histological types]. PMID- 6257944 TI - [Bronchoscopic classification of lung cancer]. PMID- 6257945 TI - [X-ray diagnosis of lung cancer]. PMID- 6257946 TI - [Concentration of tumor cells in the sputum of lung cancer--an improved method of Saccomanno's technique (author's transl)]. PMID- 6257947 TI - [Diagnosis of lung cancer by transthoracic needle biopsy]. PMID- 6257948 TI - [Computerized tomography of lung cancer]. PMID- 6257949 TI - [Bronchial artery infusion of antineoplastic agents]. PMID- 6257950 TI - [Immunochemotherapy of lung neoplasms]. PMID- 6257951 TI - [Combined use of radiotherapy and chemotherapy in the management of lung cancer]. PMID- 6257952 TI - [Multidisciplinary treatment of lung cancer]. PMID- 6257953 TI - [Small cell carcinoma of the lung: clinical studies]. PMID- 6257954 TI - [Problems in the classification of atypical small cell carcinoma of the lung]. PMID- 6257955 TI - [Ectopic hormone production of lung cancer: endocrinological studies]. PMID- 6257956 TI - [Distribution and the route of lymphatic metastasis in lung cancer]. PMID- 6257957 TI - [Degree of malignancy and prognosis of lung cancer]. PMID- 6257958 TI - [Pathology and biochemistry of carcinoid]. PMID- 6257959 TI - [A case of successfully resected minute hepatocellular carcinoma diagnosed by computed tomography (author's transl)]. PMID- 6257960 TI - [Age-related changes in endocrine mechanisms (author's transl)]. PMID- 6257961 TI - The effect of temperature acclimation on the spin-lattice relaxation time of brown adipose tissue. AB - Cold acclimation induced an increase of spin-lattice relaxation time (T1) of proton nuclear magnetic resonance in rat brown adipose tissue with concomitant increase of water content, while heat acclimation did not effect T1 of this tissue, although its water content was significantly decreased. Temperature acclimation did not affect either T1 or water content of neck muscle. PMID- 6257962 TI - [Endocrinological studies on pathogenesis on urolithiasis. III. Calcium metabolism and parathyroid function of calcium urolithiasis (author's transl)]. PMID- 6257963 TI - Changes in membrane surfaces of collecting duct cells in potassium adaptation. AB - Chronic potassium loading results in an increased capacity of the distal nephron to secrete potassium. The cellular mechanism for this adaptation has been correlated to an increase in the activity of sodium-potassium-ATPase. Because adaptation may be dependent on the greater availability of potassium pumps in the basolateral membrane, a stereologic analysis of the membrane surface area was performed to determine whether the apparent increase in pump sites was due to an increase in cell membrane surface. With potssium adaptation, the number of microplicated cells in the outer medulla was reduced from 31 to 18%. There was a marked increase in the basolateral infolding of principal cells, and membrane surface increased by 32%. In papillary collecting duct cells, the basolateral membrane surface was unchanged but the surface density of the luminal membrane increased by 50%. These observations suggest that amplification of the basolateral cell membrane to increase the number of potassium pump sites per cell plays an important role in the mechanism of potassium adaptation in the outer medulla. A different mechanism involving the luminal membrane operates in the papillary collecting duct. Structural alterations in cell membrane surfaces are thus related to the regulation of the epithelial transport of electrolytes. PMID- 6257964 TI - Aldosterone and dopamine receptors in the kidney: sites for pharmacologic manipulation of renal function. PMID- 6257965 TI - Effects of environmental chemicals on kidney metabolism and function. PMID- 6257966 TI - [Regulation of aldosterone secretion in anephric patients]. PMID- 6257967 TI - Prevalence of indigenous viruses in laboratory animal colonies in the United Kingdom 1978-1979. AB - Compared with the results of the previous serological survey of 1976-1977, it can be seen that mouse hepatitis virus is still prevalent in the mouse colonies and that corona viruses of rats are also common. The prevalence of Sendai virus has increased considerably. However, the prevalence of Reo 3 virus appeared to have decreased, although this may be the results of the different test used. PMID- 6257968 TI - Demyelination and wasting associated with polyomavirus infection in nude (nu/nu) mice. AB - Nude (nu/nu) mice bearing human tumour heterografts were affected with posterior paralysis and wasting. There was demyelination and infection of the oligodendrocytes of the spinal cord with a papovavirus. Similar virus particles and inclusion bodies were found in the bronchial epithelium, which showed histopathological changes. Similar changes were shown by the epithelia of the renal pelvis, ureter and choroid plexus. The virus was found in a transplantable human tumour, and evidence of spread by contact was also obtained. Intracerebral injection of spinal cord suspension from infected mice resulted in virus infected cutaneous carcinomata, demyelination with virus particles in the oligodendrocytes and posterior paralysis with wasting in adult nude mice. The suspension injected intraperitoneally into newborn Syrian hamsters produced tumours similar to those produced by murine polyoma. No evidence of infection was found in mice from the colony of origin. The virus was identified as murine polyoma Wild Type A2. PMID- 6257969 TI - Enterotoxaemia involving Clostridium perfringens iota toxin in a hysterectomy derived rabbit colony. AB - During an explosive outbreak of fatal enteropathic disease involving Clostridium perfringens iota (i) toxin, a total of 183 deaths occurred in 18 weeks. The clinical signs and post-mortem findings are reported. Examinations for virus, Bacillus piliformis and coccidia were negative. Clostridium perfringens i toxin was detected in 22 of 27 animals examined (81.5%), but clostridia were not isolated. Various treatments were attempted. It is concluded that i toxin and the syndrome described are closely related. PMID- 6257970 TI - Diagnostic exercise. Mouse hepatitis virus enteritis. PMID- 6257971 TI - Method to detect asymptomatic carriers of simian hemorrhagic fever virus. AB - Evidence was obtained that mononuclear phagocytic cells are the target cells for simian hemorrhagic fever virus replication. Using peritoneal macrophages from rhesus monkeys in an in vitro, 18 of 20 asymptomatic chronically infected patas monkeys were detected from coded samples. The two chronically infected patas monkeys not detected by the test, nevertheless, contained virus. This was determined by inoculating macrophage cultures with plasma from macaques dying as a result of inoculation with plasma from these chronically infected animals. in addition to virus found in chronically infected animals, all isolates of simian hemorrhagic fever virus tested previously described epizootics lytically infected rhesus monkey macrophages. These data suggested that the highly fatal nature of simian hemorrhagic fever in macaques was related to the extreme sensitivity of their mononuclear phagocytic cells to infection and lysis. PMID- 6257972 TI - Effects of a viral laryngotracheitis on the epithelial barrier of chicken airways. AB - The effects of a virus infection on the barrier function of tracheal epithelium were compared to the effects of a chemical agent (methacholine) which selectively increases membrane permeability, and both were compared to controls. The disruption of the airway epithelium induced by the virus infection caused an increased permeation of horseradish peroxidase (HRP) through this barrier. Methacholine enhanced HRP uptake from the airway lumen to the blood as compared to controls. Visualization of HRP in the tracheal epithelium by transmission electron microscopy correlated with the radioimmunoassay measurements in the blood. Serial anti-HRP antibody titers were measured by a competitive binding technique. The antigen permeation induced by methacholine was associated with an enhanced anti-HRP antibody production. The larger increase in antigen permeation seen with the viral infection was associated with depressed anti-HRP titers. It was concluded that viral disruption of the airway epithelial barrier may contribute to an increased uptake of orally inhaled antigens. The relationship, however, between the increased antigen penetration consequent to the viral infection and the development of allergy remains unclear. PMID- 6257974 TI - Leprous histiocytoma. AB - An apparently healthy male aged 18 years presented with four subcutaneous swellings. He had no history of leprosy and he did not receive any treatment for leprosy. Histological examination of one of the swellings revealed leprous histiocytoma. The histological features of the lesion have been discussed and available literature reviewed. PMID- 6257973 TI - An ultrastructural and cytochemical investigation of the development of inclusions in gastric chief cells and parietal cells of mice with the Chediak Higashi syndrome. AB - Gastric epithelium of the beige mouse, with a mutation thought to be analogous to that in Chediak-Higashi syndrome of man, has been examined by ultrastructural morphologic and cytochemical methods. The gastric chief cell in beige mice at 2 months of age or older disclosed two types of abnormal inclusion bodies each having distinctive morphologic and cytochemical features and a different distribution pattern and relationship to other organelles. On the basis of these findings, the first type of inclusion was thought to originate from zymogen granules, in a process of crinophagy, and the second type was interpreted as arising from the maturing face of the Golgi lamellae by the route for genesis of secondary lysosomes or lipofuscins. Each type of inclusion showed evidence both for participating in autophagic processes and for fusing with each other to produce giant inclusions. Additional observations in this study provided evidence for a role of Golgi endoplasmic reticulum lysosome in genesis of secretory granules and of the mature face of the Golgi complex in development of secondary lysosomes in chief cells. The findings also afforded evidence of migration of chief cells toward the bottom of the gland in the course of their maturation. The gastric parietal cell of control black mice disclosed secondary lysosomes, thought to arise from fusion between multivesicular bodies and mitochondria. These autophagic secondary lysosomes were enlarged in beige mice. PMID- 6257975 TI - Chronic cyanide exposure--A biochemical and industrial hygiene study. AB - A study was undertaken to assess the health status of workers exposed to cyanide fumes and cyanide aerosols in one of the local factories. Cyanide levels in the breathing zone and the working atmosphere were measured. Cyanide and thiocyanate concentrations in blood and urine were determined colorimetrically. The cyanide and thiocyanate concentrations in blood and urine of exposed workers were much higher than those of control workers. Smokers had higher concentrations than nonsmokers. The highest values of cyanide were found to be 0.8 and 0.2 mg/m3 in the breathing zone and general workroom atmosphere respectively. In spite of such low values, the workers complained of typical HCN poisoning. It is suggested that MAC values of 5 mg/m3 (in terms of CN) should be reviewed in respect to conditions in India. PMID- 6257976 TI - Alterations in thyrotropin (TSH) binding in iodine-deficient rats. PMID- 6257978 TI - Fatal pulmonary tumor embolization following peritoneovenous shunting for malignant ascites. AB - A 44-year-old white male with pseudomyxoma peritonei and intractable malignant ascites is described. This patient underwent three peritoneovenous shunt procedures utilizing first the LeVeen shunt and finally the Denver shunt in a surgical attempt at palliative decompression of his malignant ascites. The peritoneovenous shunts resulted in massive tumor embolization to the pulmonary vasculature, clinically asymptomatic disseminated intravascular coagulation, and partial thrombosis of the superior vena cava. The pulmonary tumor embolization was manifest clinically as moderate pulmonary hypertension with increased pulmonary vascular resistance and persistent hypoxia. PMID- 6257977 TI - Organ culture of human parathyroid glands: effects of catecholamines. PMID- 6257979 TI - Primary oat cell carcinoma of the larynx: a case history and literature review. AB - A case of primary oat cell carcinoma of the larynx is described and the literature reviewed. The origin of this rare tumor and the natural history of the disease are discussed. The different treatment modalities carried out so far are described. PMID- 6257980 TI - Male breast cancer. AB - This study comprises 27 cases of male breast cancer treated at the University Hospital from 1966 through 1978. Its incidence was 0.53% of all cancer in males and 3.2% of all mammary cancers. Mean age was 52 years old. Lump in the breast was the commonest presenting feature in all patients followed by skin ulceration in 44.4% of cases. The average duration of symptoms was 16 months. Twenty-five patients had infiltrating duct carcinoma and two had papillary carcinoma. Two cases were in stage I, 10 in stage II, 11 in stage III, and 4 in stage IV. Of the 12 patients in stages I and II who underwent radical mastectomy, the axillary lymph nodes were pathologically negative in stage I and positive in stage II. The nodes were clinically involved in stages III and IV. Simple mastectomy followed by radiotherapy were used in stage III cancer and all patients in stage IV cancer had only biopsy and palliative chemotherapy. Bilateral orchidectomy followed by estrogen gave only marginal benefit in terms of survival and objective regression. Only four patients, two each in stages I and II, are alive and well for more than five years. These include two cases of papillary carcinoma. Poor prognosis in this series was exclusively determined by axillary lymph node involvement, although other factors such as shorter span of symptoms, younger age group, higher incidence of skin involvement, and invasive nature of carcinoma also appear to be significant. PMID- 6257981 TI - Wilms tumors in adults. AB - A 63-year-old man had an unresectable metastatic Wilms tumor in the right kidney. Radiotherapy to the abdomen and chest wall as well as chemotherapy in the form of actinomycin D, vincristine, and cyclophosphamide was given. The tumor was radioresponsive but failed to respond to chemotherapy. The literature was reviewed. Other reported cases of Wilms tumor in adults treated with chemotherapy that is usually given to children are few, but the results are mostly disappointing. PMID- 6257983 TI - Postirradiation malignant fibrous histiocytoma. AB - Three patients who were treated successfully with postoperative external radiation therapy for ovarian carcinoma, endometrial adenocarcinoma and bilateral retinoblastoma respectively developed years later malignant fibrous histiocytoma (MFH) within the irradiated field. MFH is a recently described soft tissue sarcoma known for its dual fibroblastic and histiocytic differentiation resulting in a pleomorphic histologic appearance. PMID- 6257982 TI - Malignant fibrous histiocytoma: a retrospective evaluation of 24 patients. AB - Twenty-four patients with malignant fibrous histiocytoma are being analyzed: 54.2% occurred in the sixth, seventh, and eighth decades of life; 45.8% were located in the extremities. This is a soft tissue sarcoma noted for its pleomorphic histologic appearance. It is postulated that the origin cell is a histiocyte. The local recurrence of metastatic potential of this tumor is difficult to predict from its histological features. Local recurrence after complete excision is frequent. Also, there is a high incidence of distant metastases. Wide local excision with a wide margin around the tumor is the most important treatment modality. The use of postoperative radiotherapy and chemotherapy needs to be evaluated. PMID- 6257984 TI - On current-voltage relations of ionic channels. PMID- 6257985 TI - A model relating the incidence of meiotic trisomy to maternal age. PMID- 6257987 TI - Intrapulmonary gas mixing in man during infusion of isoproterenol studied by simultaneous wash-out of He and SF6. PMID- 6257986 TI - A novel kinetic mechanism explaining the non-hyperbolic behavior of metal activated enzymes. Case of choline kinase from rat liver. PMID- 6257988 TI - Heterozygous defects in alpha 1-antitrypsin and low-density lipoprotein receptor. Simultaneous occurrence in a pediatric patient. AB - alpha 1-Antitrypsin is a serum protein protease inhibitor. The homozygous deficiency state for alpha 1-antitrypsin is associated with the development of chronic obstructive lung disease and liver cirrhosis. Familial hypercholesterolemia is a genetic defect in which the nonhepatic tissues of affected persons are partially or completely deficient in cellular receptors for low-density lipoproteins, the major plasma cholesterol transport protein. Homozygotes and heterozygotes for familial hypercholesterolemia experience premature coronary artery disease. We have identified a young patient who manifested heterozygous deficiencies for both of these gene products. The occurrence of these defects in tandem has not been previously reported. PMID- 6257989 TI - [Radiotherapy of urologic tumors in childhood]. PMID- 6257991 TI - [Studies on the interference system between "cold" and "hot" mutants of Coxsackie B 6 virus]. PMID- 6257990 TI - [Studies on antibacterial activity of cephotaxime (HR 756), a new antibiotic of the cephalosporin group (author's transl)]. AB - Cephotaxime (HR 756) is a new cephalosporin antibiotic of wide spectrum and extraordinary activity, suitable for parenteral administration. It is highly resistant to the beta-lactamases of Gram negative bacilli, being thus especially active against microorganisms such as indole-positive Proteus, Serratia marcencens, and others usually resistant to most beta-lactamic antibiotics because of their ability to produce beta-lactamases of high activity. The sensitivity of 355 different bacterial strains to cephotaxime has been determined by the disc method, along with the minimal inhibitory concentration (MIC) of the drug to the same strains, and regression lines have been constructed. The extraordinary activity of cephotaxime against Enterobacteriaceae, Vibrio Cholerae, Haemophilus, and Neisseria meningitidis is noteworthy. Of the 220 strains of Enterobacteriaceae studied, 55% produced beta-lactamase. The MIC of cephotaxime for beta-lactamase forming strains was similar to that for non forming strains. PMID- 6257992 TI - [Studies on various parameters of the interference system of Coxsackie B6 viruses]. PMID- 6257993 TI - Cholesterol granuloma presenting as an isolated middle ear tumor. AB - Patients with cholesterol granuloma of the middle ear cleft will usually present with a secretory otitis media, and exhibit evidence of diffuse disease within the mastoid upon roentgenographic evaluation. The following patient with an isolated middle ear cholesterol granuloma presented with signs and symptoms more closely resembling a glomus tumor. PMID- 6257994 TI - Interrelationship of carbohydrate and the alpha-toxin binding site on the acetylcholine receptor from Torpedo marmorata. PMID- 6257995 TI - A probable site of action of diazepam in rat cerebellar GABA system. PMID- 6257996 TI - Tryptamine and 5-hydroxytryptamine: actions and interactions of cortical neurones in the rat. PMID- 6257997 TI - Functional evidence for subsensitivity of noradrenergic alpha 2 receptors after chronic desipramine treatment. PMID- 6257998 TI - Properties of [3H]diazepam binding sites on rat blood platelets. PMID- 6257999 TI - The effects of delta 9-tetrahydrocannabinol on the positive and negative feedback control of luteinizing hormone release. PMID- 6258000 TI - [Modified radiation therapy method in small-cell lung cancer]. PMID- 6258002 TI - [Iatrogenic neural lesions]. PMID- 6258001 TI - [Interstitial radiation therapy with 198Au after a radical operation for rectal cancer]. PMID- 6258003 TI - [Neuromuscular diseases in children. Differential diagnostic hints]. PMID- 6258004 TI - [Calcium-containing kidney calculi. Physiopathology and clinicochemical diagnosis]. PMID- 6258005 TI - [Angiotensin I converting enzyme in various diseases]. PMID- 6258006 TI - [Acute relapses in multiple sclerosis. Emergency diagnosis and therapy]. PMID- 6258007 TI - [Fibrogenous effect of silica dust from different soil deposits in Poland]. AB - The fibrogenous effect of the dusts from 4 samples of siliceous earth collected from different deposits in Poland has been evaluated. The studies have been carried out on white rats (males), by single intratracheal administration of 50 mg dust suspended in 0,6 cm3 of the physiological solution of NaCl. After 3 months the animals were decapitated to determine: the weight of wet mediastinal lymph nodes, the weight of wet lungs, lipids and hydroxyproline content in lungs. The hydroxyproline content was the primary index of the fibrogenous action. The results demonstrated that from among the 4 samples of siliceous earth, the siliceous earth from Piotrowice exhibited the greatest fibrogenous effect. The hydroxyproline content in rats' lungs, resulting from the effect of siliceous earth from Piotrowice was nearly 5-fold that in the animals administered with the dusts of the remaining siliceous earth samples. The mining and processing of mineral raw materials are usually related to a great dustiness in work environment, therefore deposits of the siliceous earth of the weakest fibrogenous activity should be mined to reduce the risk of the development of nonspecific diseases of respiratory tract, lungs, and pneumoconiosis in the exposed workers. PMID- 6258008 TI - Stimulation of aldosterone secretion by metoclopramide in humans: apparent independence of renal and pituitary mediation. AB - Metoclopramide (MP), a dopamine antagonist, stimulates secretion of aldosterone by a mechanism which has not been defined. We examined a potential role for either the kidney or the pituitary to mediate MPs effect on aldosterone secretion. Responses to MP administered i.v. were measured in six anephric and six hypopituitary patients as well as in six normal subjects. MP increased the plasma aldosterone concentration (PAC) in normal subjects in a fashion similar to what had previously been reported. MP produced no increase in plasma levels of renin activity (PRA), cortisol, potassium, or sodium. Three of six anephric patients (all of whom had undetectable PRA) responded to MP with increases in PAC; the magnitude of these responses correlated with the plasma potassium concentration. All six hypopituitary patients showed increases in PAC after MP administration. MP increased plasma prolactin levels in normal subjects and anephric patients; one hypopituitary patient had high basal plasma prolactin levels which increased with MP. In conclusion, neither the kidney nor the pituitary is involved in the mechanism for MP stimulated aldosterone production. These observations suggest that MP may act on the adrenal to evoke secretion of aldosterone. PMID- 6258009 TI - Direct inhibition of rat leydig cell function by tamoxifen. AB - The effects of tamoxifen on rat testicular steroidogenesis were studied using dispersed interstitial cells. Tamoxifen significantly inhibited LH-, and 8-bromo adenosine 3',5'-monophosphate (8-bromo-cyclic AMP)-stimulated testosterone synthesis in a dose-dependent manner. Tamoxifen (10(-5)M) also reduced LH stimulated cyclic AMP formation. The addition of equimolar concentrations of 17 beta-estradiol or tamoxifen separately to interstitial cells resulted in similar inhibition of LH-stimulated testosterone synthesis. When equimolar concentrations of 17 beta-estradiol and tamoxifen were added concomitantly to interstitial cells, the inhibition was additive. Present studies demonstrate that tamoxifen has direct inhibitory effects on testicular steroidogenesis: both at the plasma membrane resulting in decreased cyclic AMP formation and also at steps subsequent to cyclic AMP. PMID- 6258010 TI - The endocrinology of the opiates and opioid peptides. AB - Since the isolation of the enkephalins five yr ago, there has been an explosive increase in knowledge concerning the effects of the opiates and opioid peptides. This review deals with the interactions of opiates with the endocrine system in rat and man. The opioid peptides have been demonstrated to exert a variety of effects on pituitary hormone secretion in rat and man. In the rat, opiates stimulate growth hormone, prolactin and ACTH release and inhibit the release of the glycoprotein hormones. In man, the physiologic role of the endogenous opiates appears to be involved predominantly in ACTH and gonadotrophin regulation. Opiate effects are mainly exerted at the level of the hypothalamus but further modulating effects may occur at the pituitary and at end-organs. Opiate-induced hormonal effects appear to be mediated through dopaminergic and/or serotonergic mechanisms. Recent studies have also suggested a possible local neuromodulatory role for the opioid peptides in the control of carbohydrate metabolism and reproductive processes. PMID- 6258011 TI - Molecular cloning of the T4 genome; organization and expression of the frd--DNA ligase region. PMID- 6258012 TI - Organization of the pE194 genome. PMID- 6258013 TI - Localization of the plasmid (pKM101) gene(s) involved in recA+lexA+-dependent mutagenesis. AB - Twenty Tn5 insertion mutants of the drug resistance plasmid pKM101 have been isolated that are unable to enhance mutagenesis with ultraviolet (UV) irradiation or methyl methanesulfonate. By restriction mapping, the Tn5 insertion in each of these pKM101 mutants was shown to be within a 1.9 kb region of the plasmid genome. We have termed this segment of the pKM101 map the muc (mutagenesis: UV and chemical) gene(s). Characterization of these mutants indicated that any Tn5 insertion within the muc gene(s) abolished the ability of pKM101 to: (a) enhance spontaneous, UV and chemical mutagenesis, (b) increase host survival following UV irradiation, (c) increase the survival of UV-irradiated phage plated on irradiated or unirradiated cells, and (d) suppress the repair and mutagenesis deficiencies of a umuC- mutant. Possible models to explain the role of the pKM101 muc gene(s) in mutagenesis and repair are discussed. PMID- 6258014 TI - Restriction mapping of deletions in the nif region of the Klebsiella pneumoniae chromosome. AB - Chromosomal DNA restriction fragments carrying the nitrogen fixation (nif) and his genes of Klebsiella pneumoniae were identified in hybridization experiments using a plasmid derived from pRD1 as a radioactive probe. Restriction mapping of 26 genetically characterized chromosomal nif deletions provided a map showing the physical location of nif genes along the chromosome. PMID- 6258015 TI - Plasmid vectors derived from phage Mu allow direct selection of transformants containing cloned HindIII and PstI fragments. AB - The vector plasmids pKN001 and pKN80 both contain the EcoRi.C fragment of E.coli phage Mu DNA which codes for a killing function that is efficiently expressed upon transformation into Mu-sensitive bacteria. By in vitro insertion of HindIII fragments at the single HindIII site of pKN80 or of PstI fragments at the single PstI site of pKN001 the killing function is inactivated. The resulting plasmids have a selective advantage over the religated vector when transformed into Mu sensitive bacteria. More than 90% of the transformations contain hybrid plasmids. These results show the usefulness of Mu DNA containing plasmids pKN001 and pKN80 as vectors that allow the direct selection for recombinant plasmids. PMID- 6258016 TI - The structure of unstable constitutive revertants of mutant galOP-308::IS2-I. AB - The isolation and characterization of three unstable and constitutive revertants of mutant galOP-308 of E. coli is described. In this mutant an IS2 element is integrated between the promoter and the first structural gene of the galactose operon, and exerts a strong polar effect on the expression of the three galactose genes. In the three revertants under investigation it was observed that relief of polarity and constitutive expression of the gal-operon were accompanied by the deletion of 90% of the IS2 sequence and of various lengths of the adjacent sequences including the gal-promoter. We conclude from this result that the transcription termination signals causing strong polarity were located on the deleted part of IS2, and that in our revertants the galactose genes are now under the control of a new promoter which is apparently unstable. PMID- 6258018 TI - A restriction map of the bacteriophage T4 genome. AB - We report a detailed restriction map of the bacteriophage T4 genome and the alignment of this map with the genetic map. The sites cut by the enzymes Bg/II, XhoI, KpnI, SalI, PstI, EcoRI and HindIII have been localized. Several novel approaches including two-dimensional (double restriction) electrophoretic separations were used. PMID- 6258017 TI - Plasmid control of recombination of E. coli K12. AB - The recombination proficiency of three recipient strains of Escherichia coli K12 carrying different plasmids was investigated by conjugal mating with Hfr Cavalli. Some plasmids (e.g. R1drd 19, R6K) caused a marked reduction in the yield of recombinants formed in crosses with Hfr but did not reduce the ability of host strains to accept plasmid F104. The effect of plasmids on recombination was host dependent. In Hfr crosses with AB1157 (R1-19) used as a recipient the linkage between selected and unselected proximal markers of the donor was sharply decreased. Plasmid R1-19 also decreased the yield of recombinants formed by recF, recL, and recB recC sbcA mutants, showed no effect on the recombination proficiency of recB recC sbcB mutant, and increased the recombination proficiency of recB, recB recC sbcB recF, and recB recC sbcB recL mutants. An ATP-dependent exonuclease activity was found in all tested recB recC mutants carrying plasmid R1-19, while this plasmid did not affect the activity of exonuclease I in strain AB1157 and its rec- derivatives. The same plasmid was also found to protect different rec- derivatives of the strain AB1157 against the lethal action of UV light. We suppose that a new ATP-dependent exonuclease determined by R1-19 plays a role in both repair and recombination of the host through the substitution of or competition with the exoV coded for by the genes recB and recC. PMID- 6258020 TI - The tetracycline-resistance transposon Tn10 inhibits translocation of Tn10. AB - Using a set of overlapping deletion mutants in the tetracycline-resistance transposon Tn10, it has been established that certain regions of the Tn10 genome exert a powerful inhibition on translocation of an intact Tn10 element into the bacterial genome. Such inhibition is strongly temperature dependent: at 37 degrees C translocation is inhibited by at least a factor of 100; no inhibition of translocation is detected at 30 degrees C. PMID- 6258019 TI - Site-specific integration of an F' lac pro factor in the region of the replication origin (oriC) of E. coli. AB - An episome, F128, which carries approximately 8 x 10(4) base pairs of chromosomal DNA homologous to the lac pro region of the E. coli chromosome, has been found to integrate into the oriC region of the chromosome in a site specific reaction. While the event appears to be recA-dependent, no homology between the episome and this region of the chromosome was detected. The Hfr strains formed result from the integration of intact F128 molecules. The structure of the Hfr strains generated has been determined and their transfer properties analyzed. PMID- 6258021 TI - Tandem duplication induced by an unusual ampA1-, ampC-transducing lambda phage: a probe to initiate gene amplification. AB - Secondary attachment site lambda-lysogens were isolated in an Escherichia coli strain carrying multiple tandem 9.8 kb repeats. The repeat carried the structural gene for chromosomal beta-lactamase, ampC. One lysogen produced lysates with amp transducing activity. Three types of phages with different densities were obtained from this lysogen. The one with the lowest density was found to be a helper lambda cI857S7 phage. The other two phage showed identical restriction endonuclease fragmentation patterns. The difference in density was due to the presence or absence of phage tail. In lambda damp the right cohesive end segment was deleted in a random fashion with the majority ending between 81.0% and 82.4% of lambda. The chromosomal segment of lambda damp was most likely located at the lambda attachment site. The lambda damp DNA was compared to that of ColE1 hybrid carrying the chromosomal amp segment and a ColE1 hybrid carrying the same 9.8 kb amp repeat as the lysogen from which lambda damp was isolated. It was found that the chromosomal part of lambda damp constituted 9.8 kb, i.e. the size of one repeat. Moreover, the novel joint between adjacent repeats was present. In a lambda attB-deleted E. coli K-12 strain, lysogenic for lambda damp, highly ampicillin-resistant mutants occurred at an exceedingly high frequency. They were found to contain in the chromosome an amplified 9.8 kb repeat. This suggested that integration of the novel joint for lambda damp into the amp region gives rise to an amplifiable duplication. In E. coli lysogenized for lambda damp at lambda attB highly ampicillin-resistant clones were also found at a high frequency. These clones carried multiple tandem repeats of lambda damp DNA, each with an intact right end segment. PMID- 6258022 TI - Bacteriophage phi 1 as a gene-cloning vector in Bacillus subtilis. AB - We attempted to use Bacillus subtilis phage phi 1 as a gene-cloning vector since the phi 1 genome was found to have few cleavage sites upon digestion with several kinds of restriction endonucleases. A phi 1 stock supplied by J. Ito (University of Arizona, Tucson, USA) consisted of two phages, phi 1E1 and phi 1E2, having one and two EcoRI-cleavage sites in their genomes respectively. From the latter isolate a deletion mutant phi 1E2 delta 1 was induced to increase the size range of DNA segments to be cloned. It was demonstrated, by in vitro recombination experiments with phage rho 11 DNA, that phi 1E2 delta 1 can be used for cloning EcoRI fragments of various sizes. We analyzed the DNAs of ten phi 1 clones isolated from independent transfectants and found that six of them carried rho 11 DNA fragments inserted at either of the two EcoRI-cleavage sites. Some of the hybrid phage DNAs were found to be cleaved with BamHI and HaeIII endonucleases and the rho 11 DNA portion, whereas the parental phi 1E2 delta 1 DNA was insensitive to any of these enzymes. These hybrid phages would therefore be useful vectors for cloning foreign DNA fragments generated by cleavage with BamHI or HaeIII endonucleases. PMID- 6258024 TI - Megacinogenic plasmid from Bacillus megaterium 216. AB - Ability to produce megacin A, a bacteriocin of B. megaterium, was transferred from the strain B. megaterium 216 into auxotrophic derivatives of the strain B. megaterium KM via protoplast fusion and polyethylene-glycol-induced protoplast transformation by plasmid DNA, respectively. A 30.9 megadalton plasmid was detected in cells with MegA phenotype, and the loss of this phenotype was accompanied in each case with the elimination of that plasmid. The megacinogenic plasmid pBM309 has a single site for both BamHI and XhoI. It is cleaved by the endonucleases SalI, BglII, PstI, PvuII, and EcoRI into 3, 3, 4, 4, and 9 fragments, respectively. The physical map of this plasmid is presented. PMID- 6258023 TI - Identification of the dnaA and dnaN gene products of Escherichia coli. AB - A specialized transducing lambda phage carrying the dnaN genes of Escherichia coli specifies two proteins of about 41 and 48 kilodaltons (kd). The temperature sensitive mutations, dnaN59 and dnaA167, were found to result in altered isoelectric points of the 41 and 48 kd proteins, respectively. Thus the dnaN gene product was identified as a weakly acidic 41 and 48 kd protein. The synthesis of the dnaN gene product is greatly reduced by insertion of a transposon Tn3 in the dnaA gene and by deletion in the gene at the distal end to the dnaN gene. Temperature-sensitive dnaA mutations, on the dnaN gene product. These results indicate that the synthesis of the dnaN gene product is dependent on the structural integrity of the dnaA gene. PMID- 6258026 TI - Physical mapping of the BglI, BglII, PstI and EcoRI restriction fragments of staphylococcal phage phi 11 DNA. AB - A cleavage map of the generalized transducing staphylococcal phage phi 11 DNA has been constructed by reciprocal double digestion. All three BglI, the six BglII, the three PstI, and 11 out of 15 EcoRI sites have been mapped. The map is circular, with a total length of 42 kb, and has been divided into 100 map units. The phage DNA is cyclically permuted and has a terminal redundancy of about 11 kb. The preferential starting point and direction for packaging DNA lies at map unit 79 and proceeds towards higher map units. PMID- 6258027 TI - Transposition of Tn 1 to the Rhizobium meliloti genome. AB - A derivative of the IncP1 plasmid RP4, carrying the thermoinducible prophage Mucts62, was obtained in Escherichia coli K12 J53 (RP4). It was impossible to maintain the hybrid plasmid RP4::Mucts62 in Rhizobium meliloti GR4. Thus, it was used as a vehicle for introducing the ampicillin-resistant transposon Tn1 into the R. meliloti genome. Transposition of Tn1 did not generate auxotrophic strains, suggesting that the insertion of Tn1 into the R. meliloti genome was relatively specific. Two chromosomal hot spots for Tn1 insertion were identified by cotransductional analysis, after general transduction by phage DF2. Plasmid curing experiments, carried out by heat treatment, revealed that symbiotic plasmid(s) also contain at least one site for Tn1 insertion. PMID- 6258025 TI - Restriction and modification in Bacillus subtilis: identification of a gene in the temperate phage SP beta coding for a BsuR specific modification methyltransferase. AB - A gene coding for a modifying DNA-methyltransferase which methylates the central C in the BsuR recognition sequence 5'GGCC was identified in the genome of the temperature Bacillus subtilis phage SP beta. This gene is expressed only after induction of the prophage by either mitomycin C or UV. The presence of active methyltransferase in induced cells leads to modification of BsuR recognition sites in SP beta DNA as well as in heterologous DNA. PMID- 6258029 TI - Identification of a second cryptic lambdoid prophage locus in the E. coli K12 chromosome. AB - In addition to the cryptic lambdoid prophage genes that are known to reside at the rac locus in Escherichia coli K12 strains, a second cryptic lambdoid prophage has been located near the gal operon. This prophage was shown to contain DNA that is homologous to the QSR genes of lambda phage. PMID- 6258028 TI - Isolation of E.coli promoters from the late region of bacteriophage T7 DNA. AB - Promotor sequences recognized by Escherichia coli RNA polymerase have been isolated from bacteriophage T7 DNA using the plasmid pBRH4. T7 DNA was digested with the restriction endonuclease Hae III, Alu I, and Eco RI* and the products of these digestions were ligated into the EcoRI site of pBRH4. Cloning of Hae III and Alu I-digested T7 DNA was achieved by blunt-end ligation of these fragments to the polymerized ends of Eco-RI-cleaved pBRH4. This converts blunt-end Eco RI fragments of T7 DNA into cohesive-end EcoRI fragments. Promoter-containing T7 restriction fragments were selected by activation of the tetracycline-resistance gene located on the plasmid vector. The genomic location of each T7 insert was determined and Hpa I-cleaved T7 DNA. Two promoter-active restriction fragments are thought to contain the C and E promoters of T7. However, the majority, of the promoter-active fragments cloned map within the late gene region of T7. In vitro binding studies indicate that E. coli RNA polymerase can form heparin resistant complexes with the cloned T7 DNA promoter fragments. These results suggest that while E. coli RNA polymerase may not participate directly in the transcription of late T7 genes, promoters for this enzyme are present in this region of the DNA. PMID- 6258030 TI - Direct selection of DNA inserts in plasmid gene of kanamycin-resistance. AB - In this paper we propose a method of direct selection for hybrid DNA molecules in paromomycin-dependent E. coli cells. PMID- 6258031 TI - Polymorphonuclear leukocyte-inhibitory factor of Bordetella pertussis. III. Inhibition of Arthus reaction and peritoneal infiltration of PMN. AB - In vivo biologic effects of the polymorphonuclear leukocyte-inhibitory factor (PIF) of Bordetella pertussis were tested by using two experimentally induced inflammatory processes in mice. The intravenous injection of a partially purified extract from phase I bacteria strongly inhibited the glycogen-induced peritoneal infiltration of polymorphonuclear leukocytes (PMN) and the Arthus reactions, whereas little inhibitory activity was found in the extract from phase III bacteria. The activity was localized in the outer membrane of phase I bacteria, as was the in vitro PIF activity, and the two activities gave the same behavior in DEAE-cellulose chromatography. Therefore the observed suppression of inflammatory processes in mice is probably due to the inhibitory action of PIF on the function of PMN in vivo. PMID- 6258032 TI - [Identification of a polymyxin preparation obtained from a mutant Bacillus polymyxa strain]. PMID- 6258033 TI - [Vitamin D and its metabolites]. PMID- 6258034 TI - [Hydrocyanic acid poisoning]. PMID- 6258035 TI - The preparation, efficacy and safety of 'antigenoid' vaccine NFU1 (S-L+) MRC toward prevention of herpes simplex virus infections in human subjects. AB - Vaccine NFU1 (S-L+) MRC was prepared by high multiplicity infection of serum deprived human embryonic lung (MRC 5) cells with type 1 Herpes simplex virus. The preparative process removed inoculum virus particles and virus DNA while virus particle and DNA synthesis was inhibited by the presence of lithium chloride in the cell culture medium. The vaccine stimulated neutralising antibody in vaccinated mice and provided long-term protection against intra-vaginal challenge with type 2 herpes virus. The safety of the vaccine was confirmed by inoculation into newborn mice and cell lines of human, mammalian, and rodent origin. There was no evidence of cell transformation in vitro or of oncogenicity or teratogenicity in rodent species. It is intended to investigate the efficiency of this vaccine in human subjects. PMID- 6258036 TI - Feminization in hepatocellular carcinoma corrected by chemotherapy: a case report. AB - A 17-year-old boy with metastatic hepatocellular carcinoma and feminization became asymptomatic after administration of antineoplastic agents. Serum estradiol level, urine estrogens, and tumor estrogen receptors were changed after the treatment. Achievement of partial remission resulted in normalization of the serum sex hormone profile and disappearance of the feminization in spite of the presence of residual tumor. Thus, serum hormone levels alone cannot be used as tumor markers for control of therapy. This suggests that chemotherapy may have altered the biological behavior of the tumor, which resulted in loss of its ability to synthesize estrogen estrogen receptors. PMID- 6258037 TI - Proceedings of the tumor board of The Children's Hospital of Philadelphia: synovial sarcoma. PMID- 6258038 TI - Leptomeningeal carcinomatosis in small cell carcinoma of the lung. AB - Among 137 patients with small cell carcinoma of the lung (SCCL) treated on two consecutive protocols, leptomeningeal metastases were documented in 12 patients (9%), 10 antemortem by cerebrospinal fluid (CSF) cytology, one by myelogram, and one only at necropsy. Signs and symptoms included confusion in seven, limb weakness in six, paresthesias in three, headache in two, urinary incontinence in two, and nausea and vomiting, diplopia and neck pain in one patient each. Nine of the 12 patients had evidence of other metastases while three patients relapsed first in the CSF and one had disease only in the leptomeninges. Treatment for this complication including irradiation, intrathecal chemotherapy, or systemic chemotherapy was generally ineffective with a median duration of survival of 50 days (range 5 to 130) after diagnosis of leptomeningeal. Necropsies showed thick tumor deposits along cord, distal nerve roots, cauda equina, and in Virchow- Robbins spaces with deep invasion into adjacent neural substance in six of the seven. Leptomeningeal involvement appears to have become manifest as median survival has increased. CSF cytology should therefore be examined in patients who develop unusual neurological findings during the course of this disease and methods of prevention may need to be considered in future studies. PMID- 6258039 TI - [A case of Poland's syndrome. Brachysyndactyly and deficiency of the pectoralis major muscle]. PMID- 6258040 TI - [Benign paroxysmal torticollis in infancy]. PMID- 6258041 TI - Parvovirus infection. PMID- 6258043 TI - Bovine dermatotropic herpesvirus infections. PMID- 6258044 TI - Characterization of dopaminergic receptors in dispersed bovine parathyroid cells. PMID- 6258042 TI - Canine parvovirus vaccination. PMID- 6258045 TI - A biochemical study of receptor internalization during beta-adrenergic receptor desensitization in frog erythrocytes. PMID- 6258046 TI - Alpha-adrenergic regulation of cholinergic responses in rat parotid acinar cells. PMID- 6258047 TI - Independent desensitization of beta-adrenergic receptor-regulated magnesium transport and cyclic AMP accumulation. PMID- 6258048 TI - Lack of cross-tolerance on multiple opiate receptors in the mouse vas deferens. PMID- 6258049 TI - Changes in the fluidity of myocardial membranes during hibernation: relationship to myocardial adenosinetriphosphatase activity. PMID- 6258050 TI - Superoxide production by purified hamster hepatic nuclei. PMID- 6258051 TI - Electron spin resonance study of the autoxidation of 6-aminodopamine. PMID- 6258052 TI - Insulin action in intact mouse diaphragm. II. Inhibition of endogenous protein phosphorylation. AB - Incubation of intact mouse diaphragms with insulin in the absence of glucose resulted in a rapid inhibition of the subsequent cell-free phosphorylation of endogenous protein substrates in tissue extracts. The phosphorylation of added histone was inhibited to a lesser extent. The inhibition was observed both in the absence and in the presence of added cyclic 3'5' adenosine monophosphate. Acrylamide gel electrophoresis of phosphorylation products revealed a number of major phosphorylated polypeptides. The phosphorylation of several polypeptides was inhibited following short treatment with insulin. These results represent a novel experimental approach to the elucidation of the mechanism of the action of insulin and are consistent with our hypothesis that the inhibition of protein kinase activities in the tissue may be the first step in this mechanism. PMID- 6258054 TI - Fluorescence polarization and spin-label study of human myeloma immunoglobulins A and M. Presence of segmental flexibility. PMID- 6258053 TI - Comparative specificity of rabbit antibody populations elicited to chemically modified sDNA. PMID- 6258055 TI - [The significance of needle-shaped filaments present in the cytoplasm of vaginal cells]. PMID- 6258056 TI - Morphological and enzymological changes of small intestine of adult female rats and youngs born from madiol-treated pregnant rats. AB - Some histological and histoenzymological changes of the small intestine of adult female Wistar rats treated with Madiol were studied. The steroid did not influence the tissular aspect, but obviously stimulatory effects on protein and enzyme reactions were induced. Similar Madiol-action on the small intestine of 21 day-old young rats was observed when the steroid was administered during pregnancy to their mothers, suggesting influences on the embryonic development. PMID- 6258057 TI - Lung parenchyma response of rats stimulated with living pneumococci by respiratory way. A histologic, histochemical and electron microscopic study. AB - The pulmonary intralobular connective tissue of albino rats stimulated by a pulverized suspension of living pneumococci is the site of an abundant cell proliferation and pyronine-plasma cell reaction, having as molecular substratum enhanced activity of Alk-Ph-ase, ATP-ase, SDH-ase and LDH-ase. Cells in varying degree of plasmacytic differentiation were evidenced electron microscopically at alveolar wall level. PMID- 6258058 TI - Retrospective data on the pituitary gland response during immune and neoplastic processes. AB - A synthesis of many experimental works performed during the last ten years regarding the nonspecific response of the pituitary gland during some immune and neoplastic processes is presented. Different modalities of the response of pituitary gland cell that vary depending on the antigen type were observed. The TAB vaccine inducing a humoral immune response determined an increased secretory activity of STH and FSH cells which are involved by their secretions in the activation of protein synthesis also including antibodies. The tumoral antigens also representing a stressing factor brought about a more intense activity besides the FSH cells, the ACTH and TSH cells. PMID- 6258059 TI - [Survival rate for gastric carcinoma in relation to tumor site and stage (author's transl)]. AB - The prognosis of gastric carcinoma is particularly unfavorable. 58% of 966 patients could be resected at the time of diagnosis, only 25% radically. The absolute 5-year survival rate is 18%, the 10-year survival rate 12%. After a curative resection 43% survive 5 years and 28%, 10 years. "A priori" gastrectomy showed no advantage in our patients. Therefore we prefer resection adapted to stage and grade for gastric cancer. PMID- 6258060 TI - [Pathology of benign tumorous diseases of the mammary glands (author's transl)]. AB - Among the large number of mammary biopsies undertaken today, benign diseases and marginally normal types occupy a considerable place. Of these, those which are considered prestages of malignant tumors, simulate malignant tumors and cause difficulties in differential diagnosis (intraoperative section) are of great importance. In childhood, infantile hypertrophies must be thought of macromastia in precocious puberty, puberal macromastia in puberty; in women, of forms of chronic mastitis in the presence of retention of secretion and periductal inflammation. The best known is the fibroadenoma in the region of which Cystosarcoma phyllodes and even a lobular carcinoma in situ may develop. Undoubtedly chronic cystic mastopathy is of particular prognostic significance. Less than 5% of all forms of mastopathy are premalignant diseases. PMID- 6258061 TI - [Pharmacokinetics of cefotaxim in geriatric patients (author's transl)]. AB - The behavior of plasma concentrations after intravenous and intramuscular administration of 2 g cefotaxim (Claforan) was determined in an intra-individual cross-over comparison in 10 geriatric patients. The half-lives measured of about 2 hours were approximately twice as long as in healthy subjects. Thus an effective level is maintained over the same period with half the recommended dose of antibiotic compared with younger patients, which could be clinically relevant. PMID- 6258062 TI - [Treatment of chronic pain. New developments]. PMID- 6258064 TI - [Muscle and tendon pain. Neurophysiological basis]. PMID- 6258063 TI - [Pain physiology in humans. New perspectives]. PMID- 6258065 TI - [Spinal pain suppression through morphine]. PMID- 6258066 TI - [Spinal control of pain]. PMID- 6258067 TI - Tinea capitis in an adult (Microsporum canis). PMID- 6258068 TI - Production of phosphates enzymes by different Candida species. PMID- 6258069 TI - Purification and properties of NADPH:flavin oxidoreductase from Entamoeba histolytica. AB - Amebal NADPH:flavin oxidoreductase was purified to apparent homogeneity. Molecular weights of 40 000 and 38 000 were estimated by gel filtration and by sodium dodecyl sulfate polyacrylamide gel electrophoresis, respectively, indicating that the enzyme is composed of a single polypeptide chain. The enzyme does not contain firmly bound flavin. It exhibited 20-fold selectivity for NADPH over NADH. With the former donor it reduced riboflavin, galactoflavin, FMN, or FAD. Aerobically the reducing equivalents were passed from reduced flavin to oxygen to form hydrogen peroxide. Intact amebae do not produce peroxide when they respire. If the title enzyme functions to reduce flavin in the intact cells some electron carrier must intervene between reduced flavin and oxygen so that the final step produces water instead of peroxide. PMID- 6258070 TI - Respiration of Tritrichomonas foetus: components detected in hydrogenosomes and in intact cells by electron paramagnetic resonance spectrometry. AB - Electron paramagnetic resonance spectrometry (EPR) techniques revealed a complex set of redox components in intact respiring cells of Tritrichomonas foetus, an aerotolerant anaerobic protozoon which lacks mitochondria. One of the two main systems of terminal respiration of this organism is the hydrogenosomal system, which oxidizes pyruvate and other substrates. EPR analysis of hydrogenosome enriched fractions, prepared by differential centrifugation, revealed the presence of at least five redox components with midpoint potentials ranging from 305 to -115 mV; most of these are likely to represent iron-sulfur clusters. Signals indicating relatively stable flavin free radicals were also observed. Involvement of these multiple redox components in the electron transport system of T. foetus hydrogenosomes is suggested. PMID- 6258071 TI - Studies on glycerol kinase and its role in ATP synthesis in Trypanosoma brucei. AB - Glycerol kinase of Trypanosoma brucei has been shown to be capable of catalysing sn-glycerol-3-phosphate dependent ADP phosphorylation for ATP generation. The rate of this reaction (Vr) is sufficient to account for the observed rate of glycerol production from anaerobic glucose metabolism by intact cells and to account for net ATP synthesis. Glycerol kinase has been purified by preparing a post-nuclear, particulate fraction and solubilizing the enzyme with 0.5% (w/v) Triton X-100. This treatment results in a 3.5-fold increase in total activity, demonstrating the latent nature of particulate glycerol kinase, and an overall 10 fold increase in specific activity in the soluble fraction. The ratio of the velocities of the forward (Vf) reverse (Vr) reactions of this enzyme is altered from 21 to 170 upon solubilization. The Michaelis constants for the solubilized enzyme are KmADP = 0.12 +/- 0.04 mM, KmG-3-P = 5.12 +/- 1.47 mM, Kmglycerol = 0.12 +/- 0.05 and KmATP = 0.19 +/- 0.04 mM. Endogenous hexokinase acts as an ATP trap favouring ATP synthesis sn-glycerol-3-phosphate and ADP. This can be demonstrated in reconstituted systems using trypanosome glycerol kinase and varying hexokinase activities. Mass action inhibition of ATP synthesis by glycerol is more marked with lower hexokinase activities. High glycerol kinase activity (> 0.5 mumol/min/mg protein) has been found in the T. brucei complex of trypanosomes that produce glycerol anaerobically whereas only low activities (less than or equal to 0.03 mumol/min/mg protein) are present in Trypanosoma cruzi, Trypanosoma lewisi and Crithidia fasciculata, organisms that do not produce glycerol. Trypanosoma congolense has a glycerol kinase activity of 0.17 mumol/min/mg protein and shows poorer ATP synthesis from anaerobic glucose metabolism than organisms of the T. brucei complex. PMID- 6258072 TI - Thyroid development and disorders of thyroid function in the newborn. PMID- 6258073 TI - The course of untreated recurrent genital herpes simplex infection in 27 women. PMID- 6258074 TI - Hepatitis B virus and the prevention of primary hepatocellular carcinoma. PMID- 6258076 TI - The origin of human cancers. AB - The limited evidence available suggests that most human cancers are not caused by conventional mutagens but are more likely to be the result of genetic transpositions. Although the molecular biology of transposition is starting to be understood, the external factors that influence its frequency have not yet been studied in any detail. PMID- 6258075 TI - Interaction between estrogen and dilantin in a menopausal woman. PMID- 6258077 TI - A gene chimaera of SV40 and mouse beta-globin is transcribed and properly spliced. AB - A gene chimaera of the first exon from simian virus 40 (SV40) sequences coding for T antigen placed upstream from the third exon from mouse beta-globin, and separated by the resultant new chimaeric intron, was cloned into a bacterial plasmid. When transfected into monkey cells, the gene chimaera was transcribed, polyadenylated and spliced using the donor splice site from SV40 and the acceptor splice site from mouse beta-globin. This result suggests that a donor site from one gene can be spliced to an acceptor site from another gene. PMID- 6258078 TI - Nonjunctional acetylcholine receptor channel open time decreases during development of Xenopus muscle. PMID- 6258079 TI - Functional reactivation of the deafferented neostriatum by nigral transplants. AB - Functional deficits following brain lesions can be due not only to the disruption of conduction in specific input and output pathways passing through the site of injury, but also to the loss of important regulatory systems controlling the functional state of neuronal circuitries in areas distant from the lesion. For example, the behavioural disturbances that result from lesions of the nigrostriatal dopamine (DA) pathways can be reversed by administration of dopamine receptor-activating drugs, such as L-dopa or apomorphine. This suggests that the lesioned dopaminergic system, rather than conveying specific input and output signals, is normally acting on neuronal machineries whose activity levels are set by the activity at the dopaminergic synapses. Thus the neurological deficits resulting from these lesions are due to functional inactivation of otherwise intact neostriatal circuitries. Previous studies have shown that intracerebral transplants of embryonic substantia nigra can compensate for drug induced as well as spontaneous asymmetric motor behaviour (expressed as a tendency to move in circles towards the lesioned side), whereas the sensorimotor asymmetry, which is pronounced in rats with a unilateral lesion of the nigrostriatal DA pathway, was unaffected by the transplant. We report here that restoration of striatal dopaminergic neurotransmission by nigral transplants in animals with bilateral, complete lesions of the nigral transplants in animals with bilateral, complete lesions of the nigrostriatal DA pathways can reinstate not only certain aspects of spontaneous motor behavior, but also sensorimotor orientation and sensory attention on the side of the body contralateral to the graft. PMID- 6258080 TI - Circulating angiotensin II and adrenal receptors after nephrectomy. AB - Mineralocorticoid secretion is predominantly controlled by the octapeptide angiotensin II, which exerts trophic actions on the adrenal glomerulosa and acute regulatory effects on aldosterone biosynthesis. The trophic actions include stimulation of angiotensin II receptors and enzymes of the aldosterone biosynthetic pathway, with corresponding enhancement of the aldosterone secretory capacity of the adrenal gland. The positive regulatory action of angiotensin II on its adrenal receptors occurs with elevations of the circulating peptide concentration within the physiological range and probably contributes to the increased sensitivity of the adrenal during sodium deficiency. In this action, angiotensin II differs from other hormones which decrease their target-cell receptors. However, the increase in adrenal angiotensin II receptors following nephrectomy has been interpreted as evidence for a tonic down-regulating effect of angiotensin II on its adrenal receptors. To clarify these conflicting views we evaluated the effects of nephrectomy on adrenal angiotensin II receptors in relation to blood angiotensin II and plasma electrolyte levels. We show here that hyperkalaemia contributes markedly to the post-nephrectomy increase in adrenal angiotensin II receptors, and that circulating angiotensin II levels persist for an unexpectedly long period after nephrectomy, presumably due to tissue generation of the octapeptide. PMID- 6258081 TI - Gating of a muscle K+ channel and its dependence on the permeating ion species. AB - In excitable cells, ions permeate the cell membrane through ionic channels, some of which open and close in response to changes in the potential difference across the membrane. It has been supposed that this opening and closing (or gating) process is largely independent of the permeating ion. However, we show here that the gating of the resting potassium permeability of frog skeletal muscle depends on the species of ion which carries current across the membrane. The potassium permeability investigated allows K+ to move in across the membrane more easily than out. This property is known as inward or anomalous rectification and is shared by cell membranes of skeletal muscle, egg and certain other cells. In both egg cells and skeletal muscle fibres, the group IIIB metal ion Tl+, which can replace K+ in several other systems in experimental conditions, also permeates the inward rectifier. Indeed, Tl+ is more permeant than K+ (refs 8, 9). However, when Tl+ carries current inwards across the membrane, the inward rectifier inactivates over a brief period when the membrane is hyperpolarized, whereas when K+ carries current, the permeability increases with time under hyperpolarization. PMID- 6258082 TI - Genetic engineering and foot and mouth disease vaccines. PMID- 6258083 TI - Dendritic release of dopamine in the substantia nigra. AB - Dopamine can be released in the substantia nigra for the dendrites of nigrostriatal dopaminergic neurones, to be involved there in the self-regulation of the dopaminergic cells, to control the release of neurotransmitters from nigral afferent fibres and to influence the activity of nigral non-dopaminergic cells. PMID- 6258085 TI - Block of acetylcholine-activated ion channels by an uncharged local anaesthetic. AB - It is now thought that amine local anaesthetic compounds (procaine, lignocaine and related molecules) depress electrical activity in nerve and muscle cells by binding to sites within ion channels and blocking current flow. Such mechanisms have been proposed to account for the effects of these local anaesthetics on both the voltage-dependent sodium current and the postsynaptic actylcholine (ACh) activated ionic current. Recently, strong evidence for block of ion channels by cationic drug molecules has been obtained by recording current from single ACh activated channels in the presence of permanently charged quaternary derivatives of lignocaine. Most amine local anaesthetic compounds are, however, weak bases, present in both charged and uncharged forms at physiological pH, and some question remains as to whether a charged group is essential for blockade of ion channels. To resolve this question, we studied the action of the uncharged local anaesthetic benzocaine (ethyl-4-aminobenzoate) on postsynaptic ACh-activated endplate current and extrajunctional single channel current of frog muscle. We report here evidence that strongly suggests that benzocaine blocks ACh-activated ion channels. PMID- 6258084 TI - Cloning of cDNA of major antigen of foot and mouth disease virus and expression in E. coli. AB - Double-stranded DNA copies of the single-stranded genomic RNA of foot and mouth disease virus have been cloned into the Escherichia coli plasmid pBR322. A restriction map of the viral genome was established and aligned with the biochemical map of foot and mouth disease virus. The coding sequence for structural protein VP1, the major antigen of the virus, was identified and inserted into a plasmid vector where the expression of this sequence is under control of the phage lambda PL promoter. In an appropriate host the synthesis of antigenic polypeptide can be demonstrated by radioimmunoassay. PMID- 6258087 TI - Unique transforming gene in carcinogen-transformed mouse cells. PMID- 6258086 TI - Alterations in brain cholecystokinin receptors after fasting. AB - Cholecystokinin (CCK) is the parent molecule of a family of polypeptide hormones, some of which are secreted from the small intestine after food ingestion and stimulate both exocrine secretion and gall bladder contraction. CCK-like molecules have also been identified in the central and peripheral nervous systems. The significance of CCK in the brain is unknown, but it could mediate satiety. The satiety produced by introduction of food into the intestine can be mimicked by systemic injections of CCK and its analogues-these hormones are also effective when injected into the hypothalamus and the cerebral ventricle. Straus and Yalow showed that brain CCK levels were reduced in the cerebral cortex of both genetically obese (ob/ob) and normal mice after a 2-5-day fast. However, Schneider detected no such reduction in similar conditions and other studies have suggested a peripheral rather than central action on satiety. Using CCK of high specific activity, specific CCK receptors have been measured both in pancreatic acini and in various brain regions. We show here that fasting in mice significantly increases CCK binding due to an increased number of CCK receptors in the olfactory bulb and hypothalamus, but not in other brain regions. In contrast, insulin binding to its receptors was not altered by fasting. As the hypothalamus is known to regulate appetite, this finding supports the concept that CCK regulates satiety through interaction with this brain region. PMID- 6258088 TI - Distribution of the insertion sequence IS1 in gram-negative bacteria. AB - Translocation of DNA segments is a recombinational event seen in both eukaryotic and prokaryotic chromosomes, and it is thought to be involved in controlling gene expression and in the evolution of chromosomes. In bacteria, insertion (IS) and transposable (Tn) elements not only translocate their own DNA, but also promote the rearrangement of both bacterial chromosomes and the plasmic genomes carrying them. The insertion element IS1 is one such element which is 768 base pairs long. IS1 is involved in the generation of deletion mutations and in the fusion of two different plasmid genomes. It can also promote the translocation of DNA segments flanked by two copies of IS1 to give rise to transposable elements responsible for antibiotic resistance and enterotoxin production. We report here the distribution of the IS1 sequence in various bacterial DNAs, particularly in the family Enterobacteriaceae. Comparison of the results with the phylogenetic relationship of these bacteria suggests that IS1 was transferred from one bacterium to another after their divergence and in some bacteria the copy number of IS1 increased by translocation. The increase in the number of copies of IS1 in bacteria may increase the probability of the genetic rearrangement responsible for the generation of resistance and enterotoxin plasmids, the existence of which is a serious problem in medical microbiology. PMID- 6258089 TI - Block of Na current and intramembrane charge movment in myelinated nerve fibres poisoned with a vegetable toxin. AB - In nerve membrane, the non-linear capacity current (displacement current) is assumed to reflect the movement of intrinsic membrane charges which control the opening of specific pathways for sodium ions (Na channels). However, various discrepancies have been reported between the effects of pharmacological agents on sodium and displacment currents (for a review see ref. 1). It is generally supposed that the opening and closing of Na channels constitutes one step of multi-step system in which each configuration change may or not give rise to a measurable charge movement. New drugs affecting either sodium or displacement currents may elucidate the relationship between charge movement and the control of sodium conductance. We therefore now report a comparison of the effects of a vegetable toxin (oenanthotoxin or OETX) on both sodium current (INa) and intra membrane charge movement (Q) in Ranvier nodes. We show that OETX reversibly blocks both sodium and displacement current. Studies of INa and Q during partial supression by the toxin reveal differences in the effects of OETX on the remaining INa and Q. The findings are discussed in relation to recent models for the Na-channel gating process and for Na-channel block by local anaesthetics. PMID- 6258090 TI - Binding of an SV40 T antigen-related protein to the DNA of SV40 regulatory mutants. AB - When simian virus 40 (SV40) infects host cells, the viral genes are expressed in two phases. Early in infection, the virus genome is transcribed and translated to yield two related proteins, 'large T' and 'small t' antigens. Later the rate of synthesis of the early messenger RNA falls and the viral genes coding for the coat proteins are transcribed and translated. Early gene transcription is inhibited only when an active large T antigen is present in the cell (for review see ref. 1). These and other observations have led to the hypothesis that T antigen acts as a negative feedback repressor of its own RNA transcript. The properties of SV40 tsA mutants, which produce temperature-sensitive T antigen, provide evidence for another role of T antigen--in the initiation of viral DNA replication. Mutations around the origin of DNA replication in SV40 lead to a cis acting defect in DNA replication. These mutations fall outside the region of the A gene which codes for T antigen but within the region known to bind T antigen and the closely related and more easily prepared D2T protein which is synthesized by an adeno-SV40 hybrid virus Ad2D2 and seems to differ from SV40 T antigen only in its amino-terminal segment. Revertants of origin-defective mutants have been isolated with second site mutations within the DNA A gene coding sequence. These data support the view that T antigen modulates transcription and replication of SV40 DNA by binding to one or more sites in and around the viral origin of replication. We present here evidence to show that mutants of SV40 carrying constructed mutations in the regulatory region show reduced binding of D2T protein in vitro. This is the first demonstration in a eukaryote that a mutation in a regulatory DNA sequence alters the binding of a controlling protein in vitro. PMID- 6258092 TI - Effect of ethanol on superoxide dismutase activity in cultured neural cells. AB - Superoxide dismutase (EC 1.15.1.1) activity was investigated in several types of neural cells cultivated in the presence of 100 mM ethanol. Superoxide dismutase was inhibited by acute treatment with ethanol. Chronic treatment with ethanol specifically inhibited superoxide dismutase in glial cells. In all instances withdrawal of ethanol produced a quick return to control values. Inhibition of superoxide dismutase by ethanol may increase toxic oxygen radicals in nervous tissue. PMID- 6258093 TI - Study of some enzyme activities in cultured chick embryo brain nerve cells treated by chick embryo brain extracts. AB - Brain extracts from 8-day-old chick embryos have been shown to influence morphological development of dissociated brain cells from 7-day-old chick embryos in culture. Stimulatory effects on size of the neuronal somas and on growth of long processes were observed by adding the cytosol of the brain extract or the dialysate of the cytosol. These morphological changes parallel modifications of various enzyme activities according to the age of the cultures. Adenyl cyclase, (Na+,K+)- and Mg2+-ATPase, 5'-nucleotidase, choline acetyltransferase, and acetylcholinesterase activities were studied between 5 and 14 days of culture. Adenyl cyclase activity was strongly stimulated at 8 days by both extracts. (Na+,K+)- and Mg2+-ATPase activities were stimulated in 8-day-old cultures only by the dialysate. 5'-Nucleotidase activity was stimulated in 8-day-old cultures by the dialysate and in 11-day-old cultures by both extracts. Choline acetyltransferase activity was stimulated by the cytosol in 8-day-old cultures and by the dialysate in 11-day-old cultures. The total acetylcholinesterase activity was higher in 8-, 11-, and 14-day-old cultures treated with the cytosol. When the cells were treated with the dialysate, the activity was only higher in 14-day-old cultures. We also found that following the addition of brain extracts, the specific activity of the enzymes we studied was enhanced and became close to the values found in vivo during embryogenesis. Thus in parallel to the morphological modifications observed in nerve cell cultures treated by embryo brain extracts, biochemical variations especially involved in synaptogenesis and membrane development could be measured. PMID- 6258091 TI - Physiological and behavioral studies with muscimol. AB - Muscimol has been used to increase our knowledge of central GABAergic systems, CNS physiology, and behavior. Some studies concerning the neurophysiological and behavioral effects of muscimol and its analogs have been reviewed and analyzed. In vivo iontophoretic studies have greatly increased our knowledge of the active conformation(s) adopted by GABA during its interaction with neuronal synaptic (or extrasynaptic) receptors, and behavioral studies have supported the notion that central GABAergic systems might be involved in convulsions, extrapyramidal functions, and other behaviors. However, behavioral studies with muscimol remain difficult to interpret in terms of central GABAergic systems, especially since muscimol is extensively metabolized and since it appears to interact with membrane sites other than GABA receptors. Muscimol does not appear to be useful for reversing human neurologic-psychiatric disorders. PMID- 6258096 TI - Lack of correlation between hypothalamic serotonin and the ether-induced ACTH secretion in adrenalectomized rats. AB - The central serotonergic system was manipulated using a serotonin receptor antagonist (cyproheptadine), electrolytic lesioning of the raphe nuclei and neurochemical destruction of the serotonergic terminals in the hypothalamus. The effects of these interventions on ether-induced ACTH secretion were studied in adrenalectomized rats. Serotonin, norepinephrine and dopamine concentrations were measured in the medial basal hypothalamus (MBH) or in individual nuclei of the hypothalamus and of certain midbrain regions. Cyproheptadine pretreatment inhibited ether-induced ACTH hypersecretion in adrenalectomized animals. Neither the electrolytic lesions of the midbrain raphe nuclei, nor the neurotoxic destruction of the hypothalamic serotonergic terminals (by intraventricular administration of 5,6-dihydroxytryptamine) caused any alteration of stimulated ACTH secretion after ether inhalation and/or long-term corticoid deficiency. These results suggest a lack of correlation between the activity of the central serotonergic system and the ACTH releasing effect of ether-stress in adrenalectomized rats. PMID- 6258097 TI - Collateral circulation in a tumor of the glomus jugulare. AB - The main anastomotic collaterals between intrathecal and extracranial arteries are shown in a tumor of the glomus jugulare. The significance of these collaterals in embolization therapy is pointed out. PMID- 6258094 TI - Acetylcholine esterase sensitivity to chronic administration of diphenylhydantoin and effects on cerebral enzymatic activities related to energy metabolism. AB - The effect of chronic treatment (8 months) with diphenylhydantoin (DPH) on rat brain was studied. The activity of some enzymes related to energy transduction (lactate dehydrogenase, citrate synthase, and malate dehydrogenase; NADH cytochrome c reductase and cytochrome oxidase) and neurotransmission (acetylcholine esterase) was evaluated both in the whole brain homogenate and/or in the crude mitochondrial fraction. A clear-cut decrease of acetylcholine esterase activity was observed, the decrease continuing even after treatment was discontinued. Effects on energy metabolism and on lactate dehydrogenase, malate dehydrogenase, and cytochrome oxidase are discussed. PMID- 6258095 TI - Degree of inhibition of ACTH release by glucocorticoids in adrenalectomized rats. AB - The inhibitory effects of corticosterone, dexamethasone and prednisolone on activity of the hypothalamus-pituitary-adrenal axis were investigated in adrenalectomized rats infused with glucocorticoids for 6 h. Infusion of 202 micrograms corticosterone did not inhibit the plasma ACTH concentration, but 504 micrograms corticosterone significantly suppressed plasma ACTH levels. Infusion of 20 micrograms dexamethasone suppressed markedly the plasma ACTH concentration. These data suggest that the degree of inhibition of dexamethasone on ACTH release is about 25 times greater than that of corticosterone. The CRF content of the hypothalamus was not decreased by the administration of 202 micrograms corticosterone over a 6-hour period, but it was significantly diminished by 504 micrograms corticosterone. Infusion of 504 micrograms dexamethasone did not decrease the hypothalamic CRF content; however, infusion of 5 mg dexamethasone effectively suppressed the hypothalamic CRF content. Infusion of 2.5 mg prednisolone did not either decrease the CRF content. These data suggest that the degree of inhibition of natural steroid at the hypothalamus level is stronger than that of synthetic steroids. In rats pretreated with a single injection of dexamethasone (25 micrograms/200 g body weight) 22 h prior to the experiments, continuous infusion of 318 micrograms of dexamethasone significantly suppressed the hypothalamic CRF content, whereas infusion of 504 micrograms of dexamethasone failed to decrease the hypothalamic CRF content in the rats not pretreated with dexamethasone. This finding suggests that a latent period after the injection of dexamethasone is needed for the appearance of the inhibitory action of synthetic steroids at the level of hypothalamus. PMID- 6258098 TI - Development of the central nervous system of Aplysia in terms of the differentiation of its specific identifiable cells. PMID- 6258099 TI - Modulation of cortical release of acetylcholine by noradrenaline released from nerves arising from the rat locus coeruleus. PMID- 6258100 TI - Comparative study of the release of glutamate and GABA, newly synthesized from glutamine, in various regions of the central nervous system. PMID- 6258101 TI - The release of labeled L-glutamic acid from rat neostriatum in vivo following stimulation of frontal cortex. PMID- 6258102 TI - Calcium-dependent potassium conductance studied on internally dialysed nerve cells. PMID- 6258103 TI - The adrenoleukomyeloneuropathy complex: expression in four generations. AB - Varying combinations of leukodystrophy, myeloneuropathy, peripheral neuropathy, and primary Addison disease were identified in 14 members of four generations of a kindred of 49 persons. Of these, 26 persons from three generations were evaluated clinically. We propose that adrenoleukomyeloneuropathy (ALMN) is a rare, progressive, presumably biochemical disorder of uncertain inheritance. ALMN is expressed clinically by dysfunction of the central nervous system, peripheral nervous system, and endocrine system. We stress that suspicion of this disorder be high in evaluating uncertain neurologic disorders, and that identification of one manifestation of this complex should alert the clinician to the possibility of a different expression of the same complex in other family members. PMID- 6258104 TI - Amyloid fibril protein in familial amyloid polyneuropathy. AB - Amyloid fibril protein was purified from organs of patients with familial amyloid polyneuropathy (Nagano prefecture, Japan). When compared with amyloid fibril protein from primary amyloidosis and secondary amyloidosis, the protein from familial amyloid polyneuropathy was shown to differ in the molecular weight of the subunit. This protein subunit had the same molecular weight as the prealbumin subunit, but had a different amino acid composition: It did not contain tryptophan and cysteine. Amyloid fibril protein from familial amyloid polyneuropathy therefore differed from IgG, AA protein, and prealbumin. PMID- 6258105 TI - Motor neuron disease: decremental responses to repetitive nerve stimulation. AB - We found significant decrement of the compound muscle action potential recorded from the abductor digiti minimi muscle in response to repetitive nerve stimulation in patients with rapidly developing motor neutron disease (MND), but not in patients with slowly developing disease when measured before exercise (7.6 plus or minus 1.3% versus 1.6 plus or minus 1.6%) and 2 minutes after exercise (13.6 plus or minus 1.2% versus 0.5 plus or minus 0.5%). All patients showed repair of decrement immediately after exercise. The mean amplitude of the compound muscle action potential was significantly lower in both the rapid disease (2.9 plus or minus 0.9 mV) and slow-disease (5.2 plus or minus 1.6 mV) groups than in controls (14.5 plus or minus 1.2 mV). For individual patients, there was no correlation between amplitude of the compound muscle action potential and decrement. These data indicate that decrement in MND relates to activity of disease of the motor neuron. PMID- 6258107 TI - Therapy of acute lymphoblastic leukaemia in childhood: effects on the nervous system. AB - A number of neurological disturbances occur during the treatment of childhood malignancies with cytotoxic drugs like vincristine, methotrexate, cytosine arabinoside, cyclophosphamide, asparaginase and others. Neurological complications range from peripheral neuropathy, myopathy, myelopathy to encephalopathy with methotrexate induced encephalopathy leading to permanent brain damage or death in most cases. Irradiation of the brain can produce transient or permanent brain damage by a direct effect on nervous tissue and by altering the blood brain barrier or the blood circulation. The many conflicting reports concerning the quality of life of long-term survivors of childhood leukaemia do not give sufficient data for final conclusions. The experiences we have encountered over the past ten years seem to confirm the optimistic echo from others. There is, however, an urgent need for a prospective study to answer the all important question: will a child suffering from leukemia emerge physically and mentally unharmed after long and aggressive treatment? PMID- 6258106 TI - Treatment of Huntington disease with gamma-acetylenic GABA an irreversible inhibitor of GABA-transaminase: increased CSF GABA and homocarnosine without clinical amelioration. AB - gamma-Acetylenic GABA (GAG, RMI 71.645), a potent irreversible inhibitor of gamma aminobutyric acid transaminase, was given orally in various dosage schedules to 14 patients with Huntington disease. The biochemical effects of the drug on cerebrospinal fluid (CSF) concentrations of gamma-aminobutyric acid (GABA) and the GABA-containing dipeptide, homocarnosine, were measured in 10 of 14 patients. Treatment with GAG increased CSF concentrations of GABA and homocarnosine as compared to pretreatment values, suggesting that the drug increased brain GABA concentration. Despite this neurochemical effect, the clinical state was not improved. Except for single seizure episodes in five patients, GAG therapy was well tolerated. These results do not exclude the possibility that agents that augment CNS GABAergic function may prove useful in therapy of Huntington disease. PMID- 6258108 TI - Chronic progressive encephalitis in children with x-linked hypogammaglobulinemia. AB - This report is on six cases of a chronic relentlessly progressive encephalitis occurring in boys with congenital hypogammaglobulinemia presumably of the x linked type, which are thought to represent a separate neurological entity. Intellectual deterioration, dysarthria, spasticity, ataxia, optic atrophy and an increase of lymphocytes in the cerebrospinal fluid, were the main clinical signs. The pathological picture was that of a viral encephalitis, but all virological investigations on brain biopsies and CSF were negative. The significance of intra cisternal tubuloreticular inclusions in brain endothelial cells, similarities with chronic rubella encephalitis, and the role of the immunological deficiency are discussed. Sofar, the cause of this new type of encephalitis remains obscure. PMID- 6258109 TI - Transient brain shrinkage in infantile spasms after ACTH treatment. Report of two cases. AB - This is the report of two cases of infantile spasms, manifesting transient brain shrinkage in computerized tomography (CT) after ACTH treatment. ACTH was given for 8 weeks to a 8-months-old Japanese girl with infantile spasms. First CT performed at 2 weeks after the final ACTH injection, displayed moderate brain shrinkage. Second CT at 4 months showed marked diminution of the shrinkage. ACTH was also given for 8 weeks to a 14 months old Japanese boy with infantile spasms. First CT, just before ACTH treatment, showed mild cortical atrophy, the second at 7 days after the final ACTH injection revealed marked brain shrinkage and moderate ventricular dilatation, and the third at 2 months, disclosed mild improvement of the shrinkage. ACTH or corticoateroid has widespread effects on the developing nervous system. In animal experiments, ACTH or steroids interfere with brain growth of young rats. CT findings of transient brain shrinkage in a child with infantile spasms might suggest that intensive treatment with ACTH or steroids in infancy interferes with brain growth as seen in the results of animal experiments. PMID- 6258110 TI - Oscillatory electrographic activity in the hippocampus: a mathematical model. AB - This model of hippocampal function describes the bilaterally symmetrical interactions of the various intrahippocampal populations of neurons that are functionally homogeneous (septal and entorhinal sources of input, granule cells, CA field pyramids cells, and basket cells). Activity of each homogeneous population is described as a first order nonlinear differential equation. Parameters are simulated, with activity defined in relative units ranging from 0 to 1.0. The first 26 equations (13 identified pools in each hemisphere) were solved simultaneously by computer to produce plots of the time course of activity changes in each of the populations. The simulations performed thus far show that the model parallels certain known properties of the system: (1) there is the expected reciprocal relationship between pyramidal cells and basket cells; (2) activity can be made to oscillate or achieve steady-state, simulating EEG "theta" rhythm or low voltage, fast activity; (3) oscillation occurs where it is known to occur (CA pyramidal cells and the dentate region), where it is presumed to occur (in basket cells), and does not occur where it is known not to occur (CA pyramidal cells); (4) there is a narrow range of frequency, and attempts to increase frequency readily terminate oscillation to cause steady-state activity; (5) oscillation requires excitatory drive from the medial septum, whereas entorhinal input is relatively less important; and (6) increases in medial septal activity can increase oscillation frequency. The results also predict certain undiscovered phenomena: (1) there is a major influence of variations in decay rate of activity in various neuronal pools; (2) there is probably an ultra-slow oscillation in the CA area; and (3) the CA projection ot the entorhinal cortex seems to be important in modulating frequency and amplitude of theta rhythm. PMID- 6258111 TI - Endogenous opioids and social behavior. AB - Evidence for the hypothesis that brain-opioids mediate social affect and social attachments is summarized. Opiates and opioids are very effective in reducing social separation-induced distress vocalizations (DVs), in puppies, young guinea pigs and chicks, while opiate antagonists can increase DVs. In studies of specific social behaviors in rodents, morphine (at doses 1 mg/kg and below) decreases proximity maintenance time in socially housed animals, increased play, decreases maternal aggression but has no effect on pup retrieval. Naloxone reduces play and disrupts pup-retrieval, but has no consistent effect on proximity maintenance time of socially housed animals. In young rats tested in social learning situations, morphine delays and naloxone hasten extinction. These data are consistent with the proposition that brain opioids modulate social emotions and behaviors. PMID- 6258112 TI - Saphenous neuropathy: following coronary artery bypass surgery. PMID- 6258113 TI - The effect of vaccination of lambs with live parainfluenza virus type 3 on pneumonia produced by parainfluenza virus type 3 and Pasteurella haemolytica. PMID- 6258114 TI - Current views on the condylomatous lesions in uterine cervix and their possible relationship to cervical squamous cell carcinoma. PMID- 6258115 TI - Residual trophoblastic disease in association with partial hydatidiform mole. AB - A 10-year retrospective study was carried out of cases diagnosed as hydatidiform mole at the University of Hong Kong. Strict morphologic criteria established in a previous report were used to study the association of the partial mole syndrome with residual trophoblastic disease. Of the total of 138 cases available, 13 were found to be partial moles, 1 of which was followed by trophoblastic disease that required chemotherapy. This subsequently proved to be an invasive (partial) mole, the first example of its kind to be verified by pathology. The extent of the association between partial mole and subsequent trophoblastic disease and the spectrum of the pathologic lesions actually underlying the latter remain to be determined by further retrospective and prospective studies. PMID- 6258116 TI - [Adriamycin, cyclophosphamide and vincristine (ACO) in small cell bronchial cancer. Course of the disease and long-term follow-up]. AB - This report summarizes our experience in 94 patients with inoperable small cell bronchogenic carcinoma treated with protocols "ACO I" and "ACO II" at the West German Tumor Center Essen. Long-term follow-up is documented for a group of 50 patients who were fully ambulatory. Complete responses were obtained in 20 of 26 patients with "limited disease" and in 12 of 24 patients with "extensive disease". The median survival of all 50 patients was 12 months (10 months in "extensive disease", 21 months in "limited disease"). An analysis of relapse patterns indicated that the local intrathoracal recurrence, especially in patients with "limited disease", remains one of the main problems. The report also includes a detailed analysis of long-term survivors. With the "ACO II" protocol which is designed to study the value of maintenance therapy after aggressive induction treatment in patients with complete response, 44 patients have thus far been evaluated for response (CR 50%). The number of patients randomized for maintenance chemotherapy is still too small to draw further conclusions at this point. PMID- 6258117 TI - [Methods and problems in staging bronchial carcinomas]. AB - The evaluation of size and histological type of primary tumors of the lung and of the draining regional lymph nodes needs a very extensive diagnostic program. This means a standardized basic program (case history, physical examination, laboratory diagnosis, X-rays of the chest, cytologic evaluation of the sputum, and bronchoscopy), and further examination depending on the findings in the individual patients (lung scan, mediastinoscopy, needle biopsy, angiography, thoracoscopy, and sometimes diagnostic thoracotomy). Looking for distant metastases it is necessary to investigate the most frequently involved organs: the liver (sonography, scan, CAT scan, laparoscopy), the skeleton (scan, X-ray, biopsy), the central nervous system (CAT scan, electroencephalogram, liquor cytology, myelography), and the retroperitoneal space (sonography, CAT scan). It is absolutely necessary to follow this program in patients with small cell carcinoma. Contrary, in patients with other types of lung cancer the whole diagnostic program is indicated when clinical signs evoke suspicion of metastases. The limits of the different diagnostic procedures are discussed. PMID- 6258118 TI - [Surgical position and possibilities in bronchial carcinoma]. AB - In accordance with international statistics 25% of all patients with bronchogenic carcinoma can be treated by resection at the moment the diagnosis is established. The 5 year survival rate is in most series 25%. Important prognostic factors are: TNM-stage, histological classification, biological nature of the tumour and involvement of lymph nodes; discussed are further localisation of the primary tumour and immunological status. The summarizing statistics show that the carcinoma of squamous cell type has the best chance of a 5 year survival with a rate of more than 50%. In small-cell carcinoma extremely different 5 year survival rates between 0 and 20% are reported. In the surgical treatment it is obvious that the number of lobectomies are increasing in comparison to pneumonectomies. The postoperative mortality rate differs for "radical" pneumonectomy between 20% and 35%, for simple pneumonectomy between 7% and 10% and for lobectomy below 2%. Determinant for the postoperative course is the preoperative estimation of the risk factors. The 5 year survival rate after broncho- or angioplastic procedures varies in different series between 9,8% and 36%. In segmentectomies and wedge resections the 5 year survival rate was up to 56%. Primary palliative resections are indicated for pain reduction and improvement of the quality of life. PMID- 6258119 TI - [Immunotherapy in bronchial carcinoma]. AB - In bronchogenic carcinoma the clinical trials performed with nonspecific immune stimulation, either in its systemic or local form, suggest that in patients with early manifestations (e.g. adjuvant therapy after operation) the time of relapse may be delayed. A similar effect is perhaps obtained in studies employing tumor antigen preparations. Whether the cure rate is increased is questionable at this time. These rather disappointing results should induce us to consider other approaches to tumor immunotherapy. Results obtained in small cell bronchogenic carcinoma suggest that a manipulation of humoral immunity (e.g. by influencing circulating immune complexes) may be an additional therapeutic concept. PMID- 6258120 TI - [Problems in the histological classification of bronchial carcinomas]. AB - Different histological classifications of pulmonary tumors, proposed and adopted over the last five decades, are briefly reviewed. Referring to the revised Histological Classification of Lung Tumors that was edited by an international committee of lung pathologists for WHO in 1977, different histologic types of bronchus carcinoma are presented in separate groups. Squamous carcinoma, small cell carcinoma, adenocarcinoma, and large cell carcinoma are differentiated in supra- and subgroups. Specific problems arising in the classification of mixed or combined tumors manifesting coexistence of different histologic growth types in the same tumor, are discussed in detail. PMID- 6258121 TI - Monolayer cultures of cells originating from ultrasonically guided fine needle aspiration biopsies. AB - Explantation of small samples of tissue obtained by ultrasonically guided fine needle aspiration biopsy (0.6 mm outer diameter) from intraabdominal solid masses was performed in 25 patients. In 7 cases, the material was taken from nonmalignant tissue and in 18 from malignant lesions. Growth during 30 days or more obtained in 1 of the 7 nonmalignant cases and in 7 of the 18 malignant cases. The morphological appearance of three cultures in monolayer is demonstrated. PMID- 6258122 TI - Effect of postoperative chemotherapy and radiotherapy, on the survival of subcutaneously implanted Furth Wilms' tumor. AB - The effect of surgery, postoperative combination chemotherapy and postoperative radiotherapy was evaluated in subcutaneously implanted Wistar/Furth rat Wilms' tumor. Four groups were studied. Group A (controls, no treatment given) had a median survival of 44 days. Group B (surgical excision of the primary tumor on day 14 after implantation) showed a median survival of 77 days, with 40% tumor free long-term survivors (sacrificed on day 175). Group C (excision followed by chemotherapy consisting of vincristine, actinomycin D and adriamycin) had a median survival of 61 days with 35% tumor-free long-term survivors. Group D received the same postoperative chemotherapy as well as radiotherapy and had 55% tumor-free long-term survivors. This tumor may serve as a treatment model for some human Wilms' tumor cases who do not respond well to current therapies. PMID- 6258123 TI - Chromosomes involved in production of infectious SV40 particles in mouse/SV40 transformed Chinese hamster cell hybrids. AB - The clone 6d hybrid, capable of expressing the virus-specific T-antigen but unable to produce infectious virus particles after superinfection, presented a complete mouse (3T3-4E) chromosome complement and a significant loss of Chinese hamster (CHK/SVLP AG) chromosomes. Similar properties were displayed by a BUdR resistant derivative of the Cl 6d hybrid (Cl 6d.6BU). Three independent superhybrid clones (CL 10B, Cl 10C, Cl 11A) isolated after backcross of the Cl 6d.6BU hybrid with a nontransformed Chinese hamster kidney cell line (CHK/AG) were able to produce infectious SV40 virus. In spite of the loss of mouse chromosomes, there was no significant difference in the average number of chromosomes between the Cl 6d.6BU and the superhybrid clones. Thus, the Chinese hamster chromosomes seemed to compensate for the loss of the mouse chromosomes. Although the effect of Chinese hamster chromosomes cannot be totally disregarded, our data suggested a positive correlation between the inability to produce infectious SV40 and the presence of certain mouse chromosomes. PMID- 6258124 TI - [Endogenous opiates and schizophrenia. Treatment of acute schizophrenic psychoses with beta-endorphin]. PMID- 6258125 TI - [Cerebellar encephalitis associated with infectious mononucleosis]. PMID- 6258126 TI - [Von Willebrand's disease, with special reference to laboratory diagnosis (the ristomycin test)]. PMID- 6258127 TI - [Multiple nodular mastocytosis in adult (author's transl)]. PMID- 6258128 TI - [Multilocular cysts or polycystic nephroblastoma? Proposal for a diagnostic and therapeutic position]. PMID- 6258130 TI - [Clinical, biological, histological, ultrastructural and therapeutic studies in one case (author's transl)]. AB - The diagnosis of glucagonoma was made in a 51 year-old woman who suffered from a polymorphous dermatitis and an insulin-dependent diabetes mellitus. Denutrition was present and there was a previous history of thrombo-embolism. Immunoreactive plasma glucagon was constantly higher than 1 000 pg/ml (N less than 175). Plasma aminoacids were low. After angiographic confirmation, the tumour and part of its hepatic metastases were resected. The dermatitis disappeared soon after. Its recurrence required chemotherapy (successively mithramycin, streptozotocin, DTIC) and good clinical results were obtained. On histological examination, the cutaneous lesions consisted of an epidermal edema, and a bullous intra-epidermic detachment. The pancreatic tumour was of the trabecular type with a very important sclerosis. On electron microscopy, the tumoral cells, some with a syncitial aspect, contained granules of the D1 type. These granules are different from the typical glucagon granules. The clinical and biological features in this case are compared with those of the 41 cases of glucagonoma previously published. PMID- 6258129 TI - [Vitamin D and its metabolites. Therapeutic indications in 1980]. PMID- 6258131 TI - [Opiate receptors and sleep: a new approach to the mechanisms of action of anesthetics (alcohol and barbiturates)]. PMID- 6258133 TI - [Small cell anaplastic cancers. Imperative treatment by intensive polychemotherapy]. PMID- 6258132 TI - [Spontaneous mononucleosis due to cytomegalovirus in otherwise healthy subjects. Prospective study of 28 cases (author's transl)]. AB - Fever was a constant feature in 28 subjects with spontaneous mononucleosis due to cytomegalovirus and lasted 15 days or more in almost all cases (26/28). Blood mononucleosis and biochemical hepatic disorders were virtually always present but appeared later, so that the fever was initially thought to be "isolated". Splenomegaly was found in 39.3 p. cent of the cases. Skin rashes developed in 5 patients who had received ampicillin. Non-specific immunological abnormalities were detected in 8 of the 13 patients in whom they were looked for. The diagnosis was established by serological tests, which showed either a significant rise in, or (in patients seen at a late stage of the disease) high, sustained antibodies titers. The virus was found in blood in seven patients among the fourteen in whom it was looked for. We believe that these findings in otherwise healthy subjects could be termed "primary infection". The condition invariably followed a favourable course in the absence of any treatment. Contrary to what is observed in infectious mononucleosis, there was no sore throat and the Paul-Bunnel Davidsohn test always gave negative results. PMID- 6258134 TI - [Kawasaki syndrome in an infant from the Ivory Coast. First African case]. PMID- 6258135 TI - [Endorphins: neuromodulators and hormones (author's transl)]. AB - The discovery of opiate receptors has resulted in the isolation of endogenous morphinomimetics called endorphins. The enkephalins, which are pentapeptides, are located diffusely within the brain and are thought to act locally as neuromodulators for the release of noradrenaline, dopamine and substance P. beta endorphin, a peptide with 31 aminoacids, is released from the pituitary with ACTH during stress. The peptide sequency of the common precursor of these hormones, pro-opiocortin, is now established. PMID- 6258136 TI - [Post-operative meningitis due to obligatory anaerobic bacteria: 3 case reports]. PMID- 6258137 TI - Nuclease sensitivity of active chromatin. AB - The active regions of chicken erythrocyte nuclei were labeled using the standard DNase I directed nick translation reaction. These nuclei were then used to study the characteristics and, in particular, the nuclease sensitivity of active genes. Although DNase I specifically attacks active genes, micrococcal nuclease solubilizes these regions to about the same degree as the total DNA. On the other hand micrococcal nuclease does selectively cut the internucleosomal regions of active genes resulting in the appearance of mononucleosomal fraction which is enriched in active gene DNA. A small percentage of the active chromatin is also released from the nucleus by low speed centrifugation following micrococcal nuclease treatment. The factors which make active genes sensitive to DNase I were shown to reside on individual nucleosomes from these regions. This was established by showing that isolated active mononucleosomes were preferentially sensitive to DNase I digestion. Although the high mobility group proteins are essential for the maintenance of DNase I sensitivity in active regions, these proteins are not necessary for the formation of the conformation which makes these genes preferentially accessible to micrococcal nuclease. The techniques employed in this paper enable one to study the chromatin structure of the entire population of actively expressed genes. Previous studies have elucidated the structure of a few special highly prevalent genes such as ovalbumin and hemoglobin. The results of this paper show that this special conformation is a general feature of all active genes irregardless of the extent of expression. PMID- 6258138 TI - The transcription termination site of the ribosomal RNA operon in yeast. AB - The site at which transcription of the ribosomal RNA operon in yeast is terminated was precisely localized. First, the exact position of the 3' end of the 26S rRNA gene was mapped on the rDNA on the basis of RNA- and DNA sequence data. Next, the 3' terminus of the primary transcript, 37S precursor rRNA, was established by hybridization experiments and sequence analysis. 37S pre-rRNA appears to be just 7 nucleotides longer at its 3' end than 26S rRNA. The non coding strand around the termination site is extremely T-rich: 15 out of 18 nucleotides are T-residues. An extensive dyad symmetry is present in the sequence downstream from the termination site; a possible role of this structure in the regulation of transcription termination is discussed. The 3'-terminal 110 nucleotides of yeast 26S rRNA have approx. 50% and 60% homology with the corresponding regions of E. coli 23S rRNA and Xenopus laevis 28S rRNA, respectively. PMID- 6258141 TI - Mobile dispersed genetic element MDG1 of Drosophila melanogaster: structural organization. AB - The whole-length mobile dispersed genetic element mdg1 has been cloned from D. melanogaster genome. It contains DNA fragments described earlier as Dm225 and Dm234, Mdg1 is 7.2 kb long and framed with two direct repeats of 300-400 base pairs each. Mdg1 family is represented by about 25 copies in the genome of flies and by 200 copies in the genome of cultured cell line 67J25D. Virtually all the copies in the genome of D. melanogaster have the same restriction map. Oligo(dA) oligo(dT) regions were found within mdg1. PMID- 6258139 TI - Biochemical transformation of thymidine kinase (TK)-deficient mouse cells by herpes simplex virus type 1 DNA fragments purified from hybrid plasmids. AB - The thymidine kinase (TK) gene of HSV-1 has been cloned in Escherichia coli K12 plasmids, pMH1, pMH1A, and pMH4. These plasmids contain a 1,92Obp HSV-1 TK DNA sequence, which replaces a 2,067 bp EcoR I to Pvu II sequence of plasmid pBR322 DNA. Superhelical DNAs of plasmids pMH1, pMH1A, and pMH4 as well as plasmid DNAs cleaved by EcoR I, Hinc II, Bg1 II, Sma I, and Pvu II transformed TK-deficient LM(TK-) cells to the TK+ phenotype. A 1,230bp EcoR I-Sma I fragment purified from pMH1 DNA (and from plasmid pAGO, DNA, the parent of pMH1) also transformed LM(TK ) cells. Serological and disc PAGE studies demonstrated that the TK activity expressed in biochemically transformed cells were HSV-1-specific. The experiments suggest that the HSV-1 TK coding region may be contained within a l.1kbp DNA sequence extending from about the Hinc II (or Bgl II) cleavage site to the Sma I site. 35S-methionine labeling experiments carried out on cell lines transformed by Hinc II-cleaved pMH1 DNA and by the EcoR I-Sma I fragment showed that the TKs purified from the transformed cells consisted of about 39-40,000 dalton polypeptides. PMID- 6258140 TI - Selective release of HMG nonhistone proteins during DNase digestion of Tetrahymena chromatin at different stages of the cell cycle. AB - The possible role of LG-1, a Tetrahymena specific HMG protein found in the macronuclear chromatin (Hamana, K. and Iwai, K. (1979) J. Biochem. 86, 789-794), was examined in relation to the chromatin structure. The chromatin isolated from cells synchronized at different stages of the cell cycle contained about one molecule of LG-1 per nucleosome. Limited digestion of the chromatin with DNase I or micrococcal nuclease selectively released LG-1 with the nucleosomal core histones and H1 remained insoluble, bound to the resistant DNA. Depending on the cell stages several types of chromatin structure were distinguished by their nuclease sensitivity. However, the chromatin at different stages exhibited the similar behavior of the LG-1 release with the nucleases as a function of the degree of chromatin solubilization. The results suggest that LG-1 proteins play a role in the chromatin organization which is rather independent of the cell stages. PMID- 6258142 TI - Non-random arrangement of nucleosomes in satellite I containing chromatin of rat liver. AB - The location of nucleosomes on the nucleotide sequence of rat satellite I DNA was investigated using micrococcal nuclease, exonuclease III, and restriction nucleases as tools. Hae III cleaved the satellite DNA containing chromatin very preferentially in the linker region. Nucleosomes were found predominantly in three defined positions on the 370 bp satellite I monomer unit. This type of arrangement occurs on not more than half of the satellite DNA containing chromatin while the rest of this chromatin is arranged differently. The arrangement of nucleosomes with high probability in preferred frames and with low probability in less preferred frames may be a general phenomenon which can be discussed as a possible mechanism to modulate sequence recognition. PMID- 6258143 TI - Intraspecific diversity of nucleotide sequences within the adenine + thymine-rich region of mitochondrial DNA molecules of Drosophila mauritiana, Drosophila melanogaster and Drosophila simulans. AB - Mitochondrial DNA (mtDNA) molecules from Drosophila mauritiana, D. melanogaster, and D. simulans contain a single adenine + thymine (A+T)-rich region, which is similarly located in all molecules, but varies in size among these species. Using agarose gel electrophoresis and electron microscopy, a difference in occurrence of one EcoRI site, and a difference in size (approximately 0.7 kb) of the A+T rich regions was found between mtDNA molecules of flies of two female lines of D. mauritiana. In heteroduplexes constructed between these two kinds of mtDNA molecules, two or three regions of strand separation, each comprising single strands of unequal length, were apparent near the center of the A+T-rich region. Using the structural differences between D. mauritiana mtDNA molecules it was demonstrated the mtDNA of this species is maternally inherited. Differences in length of A+T-rich regions were also found between mtDNA molecules of two geographically separated strains of D. melanogaster, and between mtDNA molecules of two geographically separated strains of D. simulans. However, in both cases, in heteroduplexes constructed between mtDNA molecules of different strains of one species, the A+T-rich regions appeared completely paired. PMID- 6258144 TI - Circular dichroism studies of the B goes to A conformational transition in seven small DNA restriction fragments containing the Escherichia coli lactose control region. AB - The B goes to A conformational transition caused by high ethanol concentrations was studied for seven DNA restriction fragments with overlapping and known sequences. Since the DNAs are homogeneous and range in GC content from 44-63%, they permit an evaluation of the influence of DNA sequence and base composition on the B goes to A transition. Moreover, their small size (80-301 bp) minimizes precipitation artifacts. The B- form spectra (in low salt) and the transition toward the C- form (in ethanol concentrations below the B goes to A transition) agree with prior measurements on chromosomal DNAs and are similar for all seven DNAs. At higher ethanol concentrations (80%), all fragments undergo a transition to the A- form as judged by the large increase of the positive CD band at 270 nm. Difference spectra among the fragments reveal minor differences between the A- form spectra. The ethanol concentration necessary to cause this transition is 72 +/- 2% for all fragments, thus excluding a preference of the CAP-, E. coli RNA polymerase-, or lac repressor-binding sequences for the A- form. The kinetics of the B goes to A transition in 80% ethanol are biphasic; the initial rapid transition is an intramolecular B goes to A form shift and the slower transition is an aggregation (but not precipitation) of the DNA PMID- 6258146 TI - A subcloning strategy for DNA sequence analysis. AB - We describe here a new strategy of fragment preparation for sequencing procedures using endlabelled DNA fragments as substrates (2,3) which is directly applicable to DNA fragments cloned into the Pst I site of pBR322, or in modified form, to inserts into the BamH I or Sal I site of the same plasmid. Ordered sets of subclones of predetermined overlap are are generated. These can be sequenced directly without further strand- or fragment separation steps. PMID- 6258145 TI - Counterion dependent variation of DNA secondary structure in (A . T) clusters: evidence by use of netropsin as a structural probe. AB - The interaction of the oligopeptide antibiotic netropsin (Nt) with (A . T) regions of DNA is characterized by a spectrum of discrete modes. This has been revealed by viscometric analysis, at 20 degrees C and 0.2 M "counterions", for NaDNA in a preceding and for NH4DNA in this paper. The increase of DNA contour length as induced by one Nt molecule was found to depend on the special mode only, while the respective stiffening is generally higher for NH4DNA. The latter property is interpreted in terms of an enhanced flexibility, relative to that of NaDNA, of the (A . T) cluster segments before complex formation. For some of the interaction modes of the DNA-Nt systems a difference in the number of corresponding binding sites has been observed. This phenomenon is understood by assuming an influence of the counterion species upon existing equilibria between different forms of the (A . T) cluster secondary structure. Not less than 5 to 10% of the total DNA are effected in this manner. Upper limits for the local differences in the axial rise per base pair are 0.04 nm and 0.02 nm. PMID- 6258147 TI - Nuclease TT1 from Thermus thermophilus HB8 has an endonuclease activity preferential to circular DNAs. AB - Homogeneously purified nuclease TT1 from Thermus thermophilus HB8 is known as an exonuclease to produce 5'-mononucleotides. Besides the exonuclease activity, nuclease TT1 also possesses endonuclease activity preferential to superhelical (form I) and single-stranded circular DNA. Although the rate of cleavage is slower than that of form I, covalently closed circular DNA (form I') is also cleaved. Form I DNA was nicked to yield relaxed circles (form II) first, and was then nicked at the opposite site to yield unit length linear DNA (form III) which was subsequently hydrolyzed to 5'-mononucleotides exonucleolytically. Both endo- and exo-nuclease activities co-migrate on polyacrylamide gels. The general properties of the endonuclease activity are very similar to those of the exonuclease activity. The temperature optimum for endonuclease activity was 85 degrees C. The pH-optimum was in pH-range from 7.5-9.1. The enzyme was active over a wide range of Mg2+ concentrations (2.5-125 mM), and was inhibited by EDTA. A linear substrate such as (dT)8 was a competitive inhibitor for this endonuclease activity. PMID- 6258148 TI - Localization of SV40 genes within supercoiled loop domains. AB - Recent studies indicate that eukaryotic DNA is organized into supercoiled loop domains. These loops appear to be anchored at their bases to an insoluble nuclear skeleton or matrix. Most of the DNA in the loops can be released from the matrix by nuclease digestion; the residual DNA remaining with the nuclear matrix represents sequences at the base of the loops, and possibly other sequences which are intimately associated with the nuclear matrix for other reasons. Using a quantitative application of the Southern blotting technique, we have found this residual DNA from SV40 infected 3T3 cells to be enriched in SV40 sequences, indicating that they reside near matrix-DNA attachment points. An enrichment of 3 7 fold relative to total cellular DNA, was found in each of three different lines of SV40 infected 3T3 cells. Control experiments with globin genes showed no such enrichment in this residual matrix DNA. This sequence specificity suggests that the spatial organization of DNA sequences within loops may be related to the functionality of these sequences within the cell. PMID- 6258149 TI - Synthesis, restriction analysis, and molecular cloning of near full length DNA complementary to bovine parathyroid hormone mRNA. AB - DNA complementary (cDNA) to a partially purified preparation of bovine parathyroid hormone mRNA was synthesized using avian myeloblastosis viral reverse transcriptase. The PTH cDNA contained about 750 bases and was greater than 95% sensitive to digestion by S1 nuclease. Analysis of the mRNA preparation by excess RNA hybridization to the PTH cDNA revealed one rapidly hybridizing component consisting of 50% of the PTH cDNA. Sequential incubation of the PTH mRNA with reverse transcriptase and E. coli DNA polymerase I produced near full length double-stranded PTH cDNA. Of the 22 restriction endonucleases tested, double stranded PTH cDNA could be cleaved with Alu I, Mbo II, Sau 3A, Sst I, and Taq I. The restriction fragments corresponding to the 5' terminus of the sense strand were identified for the last three enzymes by comparing the size of fragments obtained from PTH cDNA before and after cleavage of the hairpin loop connecting the two strands by S1 nuclease. The restriction map of the cDNA was used to detect clones of bacteria containing recombinant plasmids with near full length PTH cDNA inserts. PMID- 6258150 TI - Identification and partial characterization of an endogenous form of mouse mammary tumor virus that is transcribed into the virion-associated RNA genome. AB - Restriction mapping demonstrated the presence of several distinct proviral forms of mouse mammary tumor virus in the genome of GR mice. One of these proviruses (GR-MTV-2) was highly amplified in GR 3A cells, a cell line derived from a GR mammary tumor. By the criterion of restriction mapping, the amplified GR-MTV-2 provirus found in GR 3A cells was identical to the provirus found in M1.19 cells, a rat cell line infected with virions obtained from GR 3A culture fluid. This result clearly implies that the GR-MTV-2 provirus in GR 3A cells was transcribed into the virion-associated viral RNA genome. Cleavage of either GR 3A or M1.19 cell DNAs with the restriction enzyme Bg1 II gave rise to a 2.6 x 10(6) dalton GR MTV-2 proviral fragment (ca. 45% of the viral genome). This fragment was isolated and mapped with thirteen restriction enzymes. PMID- 6258151 TI - The translocation inhibitor tuberactinomycin binds to nucleic acids and blocks the in vitro assembly of 50S subunits. AB - Binding studies were performed with a [14C]-labelled derivative of viomycin, tuberactinomycin 0 (TUM O). TUM O bound to 30S and 50S subunits. The binding component was the RNA, since ribosomal proteins did not bind the drug. Other RNAs such as tRNA, phage RNA (MS2), and homopolynucleotides also bound the drug. Striking differences in the binding capacity of the various homopolynucleotides were found. Poly(U) bound strongly, poly(G) and poly(C) bound intermediately, whereas poly(A) showed a very low binding. DNA also bound TUM O, although with native DNA the binding was only weak. Finally the effects of viomycin on the assembly in vitro of the 50S subunit from E. coli were tested. A very strong inhibition was found: when the reconstitution was performed at 0.5 x 10(-6) M viomycin the particles formed sedimented at about 50S, but showed a residual activity of less than 10%. The inhibitory power of viomycin with respect to the in vitro assembly is more pronounced than that found in in vitro systems for protein synthesis. PMID- 6258152 TI - A 300 MHz and 600 MHz proton NMR study of a 12 base pair restriction fragment: investigation of structure by relaxation measurements. AB - The 1H NMR spectrum of a 12 base pair DNA restriction fragment has been measured at 300 and 600 MHz and resonances from over 70 protons are individually resolved. Relaxation rate measurements have been carried out at 300 MHz and compared with the theoretical predictions obtained using an isotropic rigid rotor model with coordinates derived from a Dreiding model of DNA. The model gives results that are in excellent agreement with experiment for most protons when a 7 nsec rotational correlation time is used, although agreement is improved for certain base protons by using a shorter correlation time for the sugar group, or by increasing the sugar-base interproton distances. A comparison of non-selective and selective spin-lattice relaxation rates for carbon bound protons indicates that there is extensive spin diffusion even in this short DNA fragment. Examination of the spin-spin relaxation rates for the same type of proton on different base pairs reveals little sequence effect on conformation. PMID- 6258153 TI - Deletions and DNA rearrangements within the transposable DNA element IS2. A model for the creation of palindromic DNA by DNA repair synthesis. AB - Three derivatives of mutant ga10P-308::IS2-I of Escherichia coli were characterized by DNA sequence analysis. Deletions and DNA sequence rearrangements were observed which apparently were initiated at short A-T rich inverted repeats within IS2. Two of the mutants carried newly synthesized DNA sequences which were inverted copies of already existing IS2 sequences. Thus long stretches with twofold symmetry were formed. It is discussed whether these inverted repeats were formed by DNA repair synthesis which was initiated at the A-T rich palindromes of IS2. PMID- 6258154 TI - Mammalian cell function mediating recombination of genetic elements. AB - Recombination of segments of the SV40 genome by a variety of mechanisms is described. These include the faithful joining of linear segments that have flush termini as opposed to previously described cohesive or resected termini. Lack of involvement of viral proteins has been demonstrated for recombination of segments with homologous overlapping termini, but probably applies also to the other joining reactions. Segments of the genome that have been cleaved in such a manner as to be unable to manufacture any known viral proteins are neutral elements of genetic information, incapable of selection by replication or biological function until recombined. These recombination functions presumably are available to the host cell and any element of genetic information that can be generated in that cell. PMID- 6258155 TI - Expression of the herpes thymidine kinase gene in Xenopus laevis oocytes: an assay for the study of deletion mutants constructed in vitro. AB - When Xenopus laevis oocyte nuclei are injected with a recombinant plasmid containing the Herpes Simplex Virus (HSV) thymidine kinase (tk) gene, a 100-fold increase in tk enzymatic activity is observed. Three lines of evidence show that this increase in tk activity is a result of the expression of the HSV tk gene. First, the enzymatic activity is selectively inactivated by the IgG fraction of antiserum raised against HSV tk protein. Second, a polypeptide that comigrates with authentic HSV tk on polyacrylamide gels is synthesized uniquely by oocytes injected with the HSV tk gene. Third, the induced tk activity found in injected oocytes is capable of phosphorylating deoxycytidine, a substrate that is utilized by HSV tk but not by cellular tk. We have used these observations to establish an assay for examining the activity of mutated variants of the HSV tk gene. Two sets of deletion mutants of the tk gene were constructed in vitro. In one set varying amounts of 5' flanking and intragenic sequences are deleted. The other set is deleted at the 3' end of the gene. By testing the activity of each mutant in the oocyte injection assay we have delimited functional boundaries corresponding to the 5' and 3' termini of the HSV tk gene. PMID- 6258156 TI - The nucleotide sequence and transcript map of the herpes simplex virus thymidine kinase gene. AB - This paper presents the nucleotide sequence of the Herpes Simplex Virus thymidine kinase (tk) gene. The position on the DNA sequence corresponding to the 5' and 3' termini of tk messenger RNA have been mapped. The mRNA termini are separated by slightly more than 1,300 nucleotides. The same 2,300 nucleotide segment of tk coding strand DNA is fully protected from S1 nuclease digestion when hybridized to tk mRNA. The location and size of the mRNA-coding segment corresponds to a region of the viral DNA that is essential for tk gene expression in microinjected frog oocytes. The nucleotide sequence of the HSV tk gene exhibits an open translational reading frame of 376 codons that extends from the methionine codon most proximal to the 5' terminus of tk mRNA to a UGA stop codon approximately 70 nucleotides from the poly-A addition site. The results of these experiments indicate that the tk gene is not interrupted by intervening DNA sequences, and that certain oligonucleotide sequences adjacent to the termini of the tk gene are homologous to similarly positioned sequences common to structural genes of eukaryotic cells. PMID- 6258157 TI - Cloning and characterization of DNA sequences complementary to messenger ribonucleic acids coding for the synthesis of two surface antigens of Trypanosoma brucei. AB - Full length double-stranded complementary DNAs (ds cDNAs) could be synthesized on mRNAs enriched in sequences coding for the synthesis of the variant specific antigens (VSAs) AnTat 1.1 and AnTat 1.8 from Trypanosoma brucei brucei. The size of these ds cDNAs is about 1700 and 1850 base pairs for AnTat 1.1 and AnTat 1.8 respectively. The ds cDNAs were cloned in the plasmid pBR322; two clones harboring a copy of each coding sequence were selected. Both the hybrid-arrested translation and the positive hybridization elution methods confirmed that these recombinants contain VSA-specific inserts. A restriction map was constructed in each case. The two sequences seem to be inserted in a reversed 3'--5' orientation, respective to the plasmid polarity. The AnTat 1.8 cloned sequence is a palindrome probably due to a cloning artefact. Hybridization of the cloned DNAs with "Northern" blots of total or poly(A)+ RNA revealed in each case a single, specific band. The expression of these VSA genes appears thus to be regulated at the transcriptional level. PMID- 6258158 TI - Nucleotide sequence through the 18S-28S intergene region of a vertebrate ribosomal transcription unit. AB - We have determined the nucleotide sequence of part of a cloned ribosomal transcription unit from Xenopus laevis extending from the 3' region of the 18S gene through the 18S-28S intergene region into the start of the 28S gene. The 18S 3' region possess two tracts of high homology with the corresponding segments of other eukaryotic 18S genes (yeast and Bombyx mori) separated by a tract of low homology which in X. laevis is rich in G plus C. The first internal transcribed spacer, between the 18S and 5.8S genes, is 557 nucleotides long, very rich in G plus C (84%) and shows no sequence homology with the corresponding yeast sequence. The 5.8S rRNA sequence is revised slightly in the light of the DNA sequence. The second internal transcribed spacer, between the 5.8S and 28S genes, is 262 nucleotides long and is even richer in G plus C (88%) than the first internal spacer. 28S rRNA starts with the sequence pUCAG. This is encoded at the first of three closely linked TCAG sites in rDNA. PMID- 6258159 TI - Cloned embryonic DNA sequences flanking the mouse immunoglobulin C gamma 3 and C gamma 1 genes. AB - To investigate the DNA surrounding genes for immunoglobulin heavy chain constant (CH) regions, we have isolated two clones bearing a C gamma 3 gene and two bearing a C gamma 1 gene from a library of mouse embryo DNA fragments. The C gamma 3 clones span 8.6 kilobase pairs (kb) on the 5' side of the gene and 6.7 kb on its 3' side, while the C gamma 1 clones together span 13 kb of 5' flanking sequence and 2.5 kb of 3' flanking sequence. Restriction mapping of the C gamma 3 gene indicates that intervening sequences divide the gene into segments of domain size, as in other CH genes. Hybridization of clone fragments to restriction digests of mouse DNA indicates that both the C gamma 1 and C gamma 3 genes probably occur as single copies in the genome. Moreover, the entire cloned sequences on the 5' side of both genes appear to be unique in the genome, indicating that no large common sequences flank CH genes. Restriction data suggest that the C gamma 3 gene is 37-40 kb 5' to the C gamma 1 gene. PMID- 6258160 TI - Nucleotide sequence analysis of a region of adenovirus 5 DNA encoding a hitherto unidentified gene. AB - The nucleotide sequence of a region located on the adenovirus type 5 genome between coordinates 59.9 and 62.5 has been determined. This region comprises the 3'-termini of mRNAs coding for the hexon and the DNA binding protein. The sequence reveals the presence of an open reading frame in r-strand transcripts downstream from the hexon termination codon. The protein predicted from this region has a MW of 23,068 daltons. Based on the characteristics of the mutant Ad2ts1, which maps between coordinates 59.9 and 69.9, it is probable that the predicted protein is involved in processing of late proteins. PMID- 6258162 TI - A family of long reiterated DNA sequences, one copy of which is next to the human beta globin gene. AB - An unusually long repeated DNA sequence was identified in cloned DNA, three kb 3' to the human beta-globin gene. Other members of this repeated sequence family were isolated from a human genomic DNA library and characterized by Southern blotting techniques, electron microscopy, and solution hybridization. The copy located next to the beta-globin gene was found to be 6.4 +/- 0.2 kb long and continuous over that length. This repeated sequence family comprises about 1% of the human genome and contains 3000-4800 copies of moderate sequence divergence which are interspersed with other less-highly repeated DNA. The 6.4 kb repeated unit does not appear to be composed of any smaller tandemly repeated subunits, nor is it expressed at a high level in bone marrow cell RNA. PMID- 6258161 TI - Multiple phases of nucleosomes in the hsp 70 genes of Drosophila melanogaster. AB - The arrangement of the nucleosomes with respect to the DNA sequence has been examined in the genes coding for the major heat shock protein (hsp 70) in Drosophila. In the repressed state of the genes, the nucleosomes are precisely phased in at least three frames. PMID- 6258163 TI - Breakage of single-stranded DNA by rat liver nicking-closing enzyme with the formation of a DNA-enzyme complex. AB - The DNA nicking-closing enzyme (type I topoisomerase) from rat liver nuclei breaks single-stranded DNA. The broken strand contains a 5'-hydroxyl and tightly bound protein. The stability of this protein-DNA complex to high salt, alkali and detergent suggests a covalent linkage between the DNA and the enzyme. The observed breakage of single-stranded DNA occurs at neutral pH prior to treatment with alkali or detergent, indicating that the breakage may be the result of an interrupted nicking and closing cycle. The resulting covalent complex could represent a reaction intermediate in the overall nicking-closing reaction. PMID- 6258164 TI - A cDNA clone from Zea mays endosperm sucrose synthetase mRNA. AB - A cDNA clone for maize endosperm sucrose synthetase of 62o nucleotide pairs length was obtained by cloning double stranded DNA obtained from the total maize endosperm poly(A) RNA in pBR322, and identifying the appropriate clone by hybrid promoter translation. In Southern blotting to genomic BamHI-digested DNA, a single band only of approximately 20 Kb lights up, indicating that the sucrose synthetase gene is unique, or that closely linked copies are located on this DNA fragment. PMID- 6258166 TI - Prevention and treatment of viral infections: problems and current recommendations. AB - Childhood immunization unfortunately has ceased to be an important focus of preventive medicine in the United States. Although smallpox is no longer a problem, vaccination against poliomyelitis, measles, and rubella is still very much needed. Immunization is also available for hepatitis B, influenza, and rabies and can be carried out in children or adults under selected circumstances. The antiviral drugs now being used have limited roles, although new drugs on the horizon seem promising. PMID- 6258167 TI - Discrepancies between bone ash and toe ash during aflatoxicosis. AB - Graded levels of aflatoxin (0, .625, 1.25, 2.5, 5.0, and 10.0 micrograms/g diet) were incorporated into a broiler-starter ration and fed to chicks from 1 day to 3 weeks of age. The tibias and middle toes were removed, and both bone ash and toe ash were determined. Toe ash significantly (P less than .05) increased at the aflatoxin levels of 2.5 ppm and above, while bone ash significantly (P less than .05) deceased at the same aflatoxin levels (2.5 ppm and above). The increase in toe ash could be partially attributed to a significant (P less than .05) decrease in toe lipid levels at the aflatoxin levels of 2.5 ppm and above. The data indicate that aflatoxin inhibits bone mineralization. The data also show that toe ash does not in all experimental designs reflect bone ash and that data interpreted solely on toe ash determination may not accurately reflect bone mineralization. PMID- 6258165 TI - A sequence-specific endonuclease (Xmn I) from Xanthomonas manihotis. AB - A type II restriction endonuclease Xmn I with a novel site specificity has been isolated from Xanthomonas manihotis. Xmn I does not cleave SV40 DNA, but cleaves phi X174 DNA into three fragments, which constitute 76.61%, 18.08% and 5.31% of the total length of 5386 base pairs, and cleaves pBR322 DNA into two fragments of 55.71% and 44.29% of the entire 4362 base pairs. The nucleotide sequences around the cleavage sites made by Xmn I are not exactly homologous, but they have a common sequence of 5' GAANNNNTTC 3' according to a simple computer program analysis on nucleotide sequences of phi X174 DNA, pBR322 DNA and SV40 DNA. The results suggest that the cleavage site of Xmn I is located within its recognition sequence of 5' GAANNNNTTC 3'. PMID- 6258170 TI - [Fluorescence microscopy determination of estrogen receptor activity in breast cancer]. PMID- 6258169 TI - [Early diagnosis of breast cancer]. PMID- 6258168 TI - [Studies on the plasma levels of cyclic adenosine-3'5'-monophosphate and cyclic guanosine 3',5'-monophosphate in patients with obstructive airways disease before and after acetylcholine-induced bronchoconstriction (author's transl)]. PMID- 6258171 TI - Rhinovirus inactivation by aqueous iodine in vitro and on skin. PMID- 6258172 TI - Dietary fibres. VI: Binding of fatty acids and monolein from mixed micelles containing bile salts and lecithin. PMID- 6258173 TI - Protease inhibitors modify induction of endogenous type C oncornavirus. PMID- 6258175 TI - Coxsackie B3 myocarditis in athymic mice. PMID- 6258174 TI - Effect of captopril on the blood pressure response to angiotensin I in turkeys. PMID- 6258176 TI - Studies on the mechanism of mucin secretion by cells of the porcine tracheal epithelium. PMID- 6258177 TI - Differentiation of opiate receptors in the brain by the selective development of tolerance. AB - The selective development to either the delta-opiate receptor agonist D-Ala2,D Leu5-enkephalin (DADL) or the mu-agonist sufentanyl (SUF) has been studied in the central nervous system of rats by use of osmotic minipumps for chronic administration of the drugs. The opiate-sensitive parameters analgesia and catatonia were investigated. Chronic intracerebroventricular infusion of DADL for 7 days produced a 15-fold shift in that for catatonia. In these rats, the potency of SUF in inducing analgesia and catatonia did not differ between DADL-treated animals and saline-infused controls. Similarly, chronic infusion of SUF resulted in tolerance towards SUF for both analgesia and catatonia. In these animals, DADL displayed a similar degree of tolerance w.r.t. its ability to evoke analgesia, whilst no tolerance could be detected for DADL-induced catatonia. The data indicate that prolonged stimulation of specific opiate receptors in the brain by selective agonists may bring about the selective development of tolerance for particular receptors. The data conflict with the notion that mu-receptors specifically mediate analgesia and delta-receptors catatonia. PMID- 6258178 TI - The role of central serotonergic mechanisms on head-twitch and backward locomotion induced by hallucinogenic drugs. AB - Head-twitch induced by lysergic acid diethylamide, mescaline and 2,5-dimethoxy-4 methylamphetamine (DOM) was significantly increased by medial raphe (m-R) lesions, but dorsal raphe (d-R) lesions did not produce any changes. Hallucinogen induced head twitch was inhibited by methysergide and tended to be increased by PCPA. These results suggest that 5-HT receptors innervated with the ascending 5 HT pathway originating in the m-R play a vital role in the manifestation of hallucinogen-induced head-twitch. That is, increase of head-twitch is ascribed to supersensitivity of 5-HT receptors. On the other hand, DOM-induced backward locomotion was inhibited by m-R or both dorsal and medial raphe lesions and methysergide, and was reversed to forward locomotion, differently from the hallucinogen-induced head-twitch. A reversion of backward locomotion was not obtained with d-R lesions or PCPA treatment. PMID- 6258179 TI - [Different methods of demonstrating veno-lymphatic correlations at a clinical examination]. AB - The authors have tried to show the close link between the lymphatic and venous systems. They describe the clinical aspects which cause us to note that one or other of these systems is the more affected, and they bring to mind aetiological theories on the origin, either congenital or acquired, of the affection. This leads to considerations clarifying the clinical and anatomo-pathological data. PMID- 6258180 TI - Transport adenosine triphosphatases: properties and functions. PMID- 6258181 TI - Voltage-dependent channels in planar lipid bilayer membranes. PMID- 6258182 TI - The action of leukotriene B4 (LTB4) on the lung. AB - The actions of leukotriene B4 (LTB4), a member of a newly discovered pathway of metabolism of arachidonic acid, were investigated both on the guinea-pig perfused lung preparation and on the parenchymal strip and compared to histamine and Slow Reacting Substance of Anaphylaxis (SRS-A). LTB was prepared from human polymorphonuclear leukocytes, extracted and purified by chromatography (Silicic acid and HPLC) and its purity was determined by gas chromatography and mass spectrometry. LTB4 is three times more potent than histamine (molar concentration) to contract the parenchymal strips and the contraction to LTB4 as well as to SRS-A lasted longer. The contraction to LTB4 is blocked by indomethacin (20 micrograms/ml), reduced by polyphloretin phosphate (50 micrograms/ml) and unaffected by FPL-55712 (1 micrograms/ml). Following its injection in the pulmonary artery of a perfused lung, LTB4 (1 microgram) induced the release of RCS (Rabbit Aorta Contracting Substance: a mixture of prostaglandins and thromboxanes) which can be abolished by indomethacin (1 microgram/ml). These findings suggest (a) that in the lung, LTB4 is a myotropic agent three times more powerful than histamine (b) that LTB4 stimulated a receptor which is different of histamine of SRS-A receptors, and (c) that its contractile action in the lung is mediated by prostaglandins and thromboxanes. PMID- 6258183 TI - The effect of hypercholesterolaemia on the lipid composition and ability of human platelets to accumulate cyclic AMP. AB - Washed human platelets from seventeen hypercholesterolaemic subjects were compared to those from seventeen age and sex matched controls with respect to lipid composition and ability to accumulate cyclic AMP. No significant difference in platelet lipid composition was found in terms of total cholesterol, phospholipid or the ratio of cholesterol to phospholipid. There was no significant different in basal levels of platelet cyclic AMP between the two groups. Platelets from hypercholesterolaemic subjects showed an impaired ability to accumulate cyclic AMP compared with controls when challenged with prostaglandins (PG) I2, D2 and E1. The platelet inhibitory actions of PGI2, PGD2 and PGE1, which are mediated by cyclic AMP are thought to be important mechanisms for the control of platelet-platelet and platelet-vessel wall interaction. Thus, an impaired response to these three prostaglandins may be relevant to our understanding of the role played by the platelet in mediating vessel wall pathology caused by hypercholesterolaemia. PMID- 6258184 TI - Regulation of cyclic AMP levels in human lymphocytes and lymphoblasts by prostaglandins. AB - The sensitivity of human lymphocytes to prostaglandins was compared to that of two lines of cultured lymphoblasts. It was found that 25 nM PGE1 increased lymphocyte cyclic AMP levels twofold, but had no effect on lymphoblasts. At 2.8 micrometers PGE1 the increase of cyclic AMP in lymphocytes was 14 fold versus a 1 3 fold increase in lymphoblasts. Lymphoblasts maintained a response to 6-keto PGE1, isoproterenol and histamine similar to that observed in lymphocytes. Thus, it appears that the rapidly proliferating lymphoblasts excape signals inhibiting proliferation by impairing the function of the PGE receptor. PMID- 6258185 TI - The effect of 6-keto-prostaglandin E1 on human lymphocyte cAMP levels. AB - 6-keto-PGE1 was capable of increasing cyclic AMP levels of peripheral human blood lymphocytes in a dose and time dependent fashion. The response was maximal after 30 min of incubation at 37 degrees C; 1 microgram per ml of 6-keto-PGE1 elevated cyclic AMP levels 5 fold which compares with a 10 fold increase due to PGE1. Thus 6-keto-PGE1 may play a role as a modulator of lymphocyte function. PMID- 6258186 TI - Dissociation of TSH adrenocortical disturbances in endogenous depression. AB - To evaluate a possible interaction between the pituitary-thyroid axis and the pituitary-adrenal axis, we measured serum levels of thyrotropin (thyroid stimulating hormone; TSH), the maximal TSH response (delta max TSH) to thyrotropin releasing hormone (TRH), serum and cerebrospinal fluid (CSF) levels of cortisol, urinary excretion of cortisol, and the plasma levels of adrenocorticotropic hormone (ACTH) in 20 patients with endogenous depression before and after electroconvulsive therapy. No significant correlations were found between serum TSH or delta max TSH on the one hand, and serum and CSF cortisol or urinary excretion of cortisol on the other hand. A direct correlation was found between serum cortisol and plasma ACTH. PMID- 6258187 TI - Platelet and erythrocyte-membrane adenosine triphosphatase activity in depressive and manic-depressive illness. AB - An investigation of Mg2+ and (Na+ + K+)-dependent adenosine triphosphatase (ATPase) activities in the platelet and erythrocyte membrane of 44 depressive and 44 manic-depressive patients was carried out before and during (for 3 weeks to less than 1 year) drug treatment. When compared with normal controls (n = 43), the patients showed significantly elevated enzyme activities during both the drug free and drug treatment periods. No remarkable changes in enzyme activities were observed between the drug-free and drug treatment (even long-term drug treatment) periods. Results suggest an alteration of cell-membrane activity, which may reflect changes in (1) ATP level, (2) cationic balance, (3) membrane phospholipid, or some combination thereof. PMID- 6258188 TI - The effects of delta 9-tetrahydrocannabinol alone and in combination with cannabidiol on fixed-interval performance in rhesus monkeys. AB - It has been reported that cannabidiol (CBD) antagonizes the effects of delta 9 tetrahydrocannabinol (THC) on operant behavior in rats and pigeons. We have replicated this finding with rhesus monkeys. Four rhesus monkeys were trained to lever press on a fixed-interval 5-min schedule of food presentation with a 1-min limited hold and 1-min time out between successive intervals. The effects of 0.3 and 1.0 mg/kg THC alone were determined three times during the experiment; before the CBD-THC interaction, after the CBD-THC interaction and once with the CBD vehicle. A dose of 30 mg/kg CBD, which alone resulted in a 24% reduction in responding, completely antagonized the response rate reduction produced by 0.3 mg/kg THC. The effects of THC revealed a rate-dependent effect that did not conform to the log-linear rate-dependency plots described for most other drugs. PMID- 6258189 TI - Modification of radiation sensitivity of cultured cells by pre- and postirradiation incubation with dibutyryl cyclic AMP. PMID- 6258190 TI - The initial early distribution of monomeric 230Pu and 241Am in rat liver as determined by Triton WR 1339 injection. PMID- 6258191 TI - Protection of normal tissue against late radiation injury by WR-2721. PMID- 6258192 TI - [Changes in the cAMP system of thalamus/hypothalamus and in the thymocytes of Syrian hamsters following melanoma transplantation (author's transl)]. PMID- 6258193 TI - The role of pancreatic venous sampling in the localization of occult insulinomas. AB - The palpation and enucleation of occult insulinomas (less than 15 mm) can be a difficult surgical problem even with good arteriographic localization. In the authors' limited experience, confirmation of arteriographic findings by pancreatic venous sampling provided little additional localizing information. However, if arteriography is negative or equivocal, venous sampling can indicate the segment of pancreas to be "blindly" resected if the adenoma is not palpable. Venous sampling may be misleading in polyendocrine syndromes because of the frequency of multiple adenomas and variable hormone production. PMID- 6258194 TI - [Gene structure of acute leukemia viruses and its transforming proteins (author's transl)]. PMID- 6258195 TI - Preparation of two dinor-PGI2 metabolites from 6-keto-PGF1 alpha by Mycobacterium rhodochrous. AB - The transformation of 6-keto-PGF1 alpha to two prostacyctin metabolites, 2,3 dinor-6-keto-PGF1 alpha (I) and 2,3-dinor-6,15-diketo-13,14-dihydro-PGF1 alpha (II) by Mycobacterium rhodochrous UC-6176 is described. The finding that the bacterium oxidized 6-keto-PGF1 alpha to the 6,15-diketo metabolite II shows that it contains 15-hydroxy prostaglandin dehydrogenase and delta 13 reductase enzyme systems. PMID- 6258196 TI - Effect of prostacyclin on platelet-activating factor induced rabbit and platelet aggregation. AB - In this paper, the effect of prostacyclin (PGI2) on the aggregation induced by Platelet-activating factor (PAF), a phospholipid mediator of anaphylaxis, was studied. Synthetic PGI2 and PGI2-like activity generated from rabbit aorta were demonstrated to be effective inhibitors of PAF-induced rabbit platelet aggregation and release of 3H-serotonin (3H-5HT). PMID- 6258198 TI - [Dental consequences of endocrine diseases]. PMID- 6258197 TI - Rapid extraction of oxygenated metabolites of arachidonic acid from biological samples using octadecylsilyl silica. AB - A rapid procedure for the efficient extraction of prostaglandins, thromboxanes and hydroxy fatty acids from urine, plasma and tissue homogenates has been developed. Fractions containing these substances are acidified and passed through a column of octadecylsilyl silica, which retains oxygenated metabolites of arachidonic acid. Phospholipids, proteins and very polar materials either are not retained or can be eluted with dilute aqueous ethanol. Nonpolar lipids and monohydroxy fatty acids are then eluted with petroleum ether or benzene. Subsequent elution of the column with methyl formate gives a fraction containing prostaglandins and thromboxanes which is much less contaminated with extraneous material than that obtained by conventional extraction of aqueous media with organic solvents. The methyl formate can be removed rapidly under a stream of nitrogen and the components of the sample purified directly by high pressure liquid chromatography (HPLC). An improved method for the purification of prostaglandins and TXB2 by HPLC on silica columns is reported. PMID- 6258201 TI - [Insulinoma and hyperinsulinism. Considerations on 8 and 4 cases respectively]. PMID- 6258200 TI - The frequency of Epstein-Barr virus infection and Burkitt's lymphoma at high and low altitudes in East Africa. AB - Burkitt's lymphomas (BL) is frequent in the tropical lowland of Africa but rare- even in the tropics--at altitudes higher than 5,000 feet above sea level. Serological surveys were carried out in Uganda and Tanzania to see whether the variation in BL incidence from high to low areas is paralleled by a variation in the extent of infection with the putative Epstein-Barr virus. Sera were collected from samples of the general child population living at high and low altitudes in the West Nile District in Uganda and in North Mara, Tanzania. All sera from these surveys were tested for anti-EBV antibodies to Viral Capsid Antigens (VCA) and to Early Antigens (EA) at the International Agency for Research on Cancer in Lyon, France. The results showed that both the prevalence and the strength of positive EBV (VCA and EA) titres are nearly similar in the lowlands and on the high plateux in East Africa. This lack of association between BL incidence and extent of EBV infection fails to support the notion of a causal role between the virus and the tumor, but does not totally exclude this possibility since some other environmental factor which is essential for BL development, may have a geographical distribution that parallels that of BL. PMID- 6258199 TI - [Spine deformities induced by irradiation of Wilm's tumors (author's transl)]. AB - A follow-up study on spine deformities of 59 consecutive Wilm's tumors treated between 1950 and 1963 was conducted. The selected cases had no metastasis at any time and had reached end of growth (16 years old of bone age). Treatment was surgery, chemotherapy and radiationtherapy mostly was 200 KV and partially with CO 60. This study showed 65p. 100 kyphosis greater than 10 degree between T9 and L3 (normal less than 5 degree) and 40p. 100 scoliosis both induced by alteration of vertebral growth and by sclerosis of soft tissues. -- Kyphosis even slight seemed to induce more pain in adult age than scoliosis. -- This work demonstrates also that growth spurt produces increased deformities. Therefore it is necessary to wait the end of growth before the evaluation of the results. Finally the most important for prevention is to irradiate as symmetrically as possible in the 3 planes of the body. The results of surgical treatment are reported and principles of early bracing for prevention are mentioned. PMID- 6258202 TI - Rotavirus infections in calves in dairy herds. AB - Neonatal calf diarrhoea was studied in 115 calves of one dairy herd from January 1976 to June 1977. Two syndromes could be distinguished: a mild and short lasting 'early diarrhoea' within the first three days of life and a usually more severe 'late diarrhoea' from the fourth to the 14th day of life. The latter type of diarrhoea occurred almost exclusively during the first half of the year. Thirty four out of 45 calves with late diarrhoea excreted rotaviruses, whereas only one of 34 calves with early diarrhoea excreted virus. In addition, rotavirus excretion was found in 11 calves that either remained healthy or had recovered from diarrhoea before virus was first detected. Similar findings were obtained in the spring of 1978 but in addition bovine coronavirus was recovered from four calves with late diarrhoea and from three healthy calves. One faecal sample obtained from a calf with diarrhoea on day 2 yielded K99+ Escherichia coli. Nearly all cows excreted rotavirus-specific antibodies in their colostrum but no relationship was found between the initial colostral antibody titre against rotavirus and the development of rotavirus-associated diarrhoea in the calf. PMID- 6258203 TI - Rotavirus infections in calves: efficacy of oral vaccination in endemically infected herds. AB - A commercially available modified live reovirus-like (rotavirus) vaccine proved innocuous in calves deprived of colostrum and protected one out of three calves against challenge 72 h after vaccination. The vaccine was evaluated in two dairy herds in the 1977 calf season. No significant differences were observed in the incidence rates or severity of undifferentiated neonatal calf diarrhoea or rotavirus-associated late diarrhoea between calves given a placebo (76) and vaccinated (74) calves in these herds. Samples of colostrum contained specific antibodies against rotavirus and neutralisation of the vaccine virus by colostral antibody in the intestinal tract was considered the major reason for the failure of the vaccine to reduce the incidence of neonatal diarrhoea in these herds. PMID- 6258204 TI - An epidemic of Getah virus infection among racehorses: isolation of the virus. AB - During the autumn of 1978 a disease characterised by fever and occasionally by exanthema and/or oedema of the limbs was seen in approximately 13 per cent of horses in a training stable in the Kanto district of Japan. A virus was isolated by the intracerebral inoculation of one-day-old mice from blood and nasal swabs taken from naturally and experimentally infected horses. The virus was subsequently passaged in two monkey kidney cell lines in which it produced complete cytopathic changes. Infected horses developed neutralising, complement fixing and haemagglutinin inhibiting antibodies to the virus and the results of serological investigations indicated that approximately 56 per cent of horses in the training centre had been infected. The virus was subsequently identified as Getah virus, a member of the alphavirus subgroup of Togaviridae. PMID- 6258205 TI - An epidemic of Getah virus infection among racehorses: properties of the virus. AB - A virus (Sakai) which had been recovered from an outbreak of disease in horses was found to be a small spherical enveloped RNA virus with a diameter of approximately 70 nm and a buoyant density of 1.22 g per ml. It grew well and produced a cytopathic effect in a variety of cell cultures; it was sensitive to organic solvents, heat and low pH. It agglutinated goose erythrocytes in a 0.35 M sodium chloride solution at an optimum pH of 6.2 and was antigenically identical or closely related to Getah virus, a member of the alphavirus subgroup of the Togaviridae. PMID- 6258206 TI - [Tumors of ovary and testis (author's transl)]. PMID- 6258207 TI - [Progress in the treatment of bronchial carcinoma (author's transl)]. PMID- 6258208 TI - [Recent concepts on the treatment of lesions of the bronchial plexus]. PMID- 6258209 TI - [A case of an adenoma secreting ACTH]. PMID- 6258210 TI - [Post paralytic facial spasm: new pathogenetic findings (author's transl)]. AB - The study of the early blink and lip reflex components in patients with postfacial palsy contracture and mass contractions shows changes in the synaptic organization of the facial nucleus. The possible contribution of nuclear factors to the altered function of reinnervated facial muscles is discussed. PMID- 6258211 TI - [Serological evaluation of vaccine against human encephalitis caused by Rocio virus]. PMID- 6258212 TI - Immunological studies of an antiviral monoclonal IgG cryoglobulin. PMID- 6258213 TI - [Unstable co-mutants produced by IS dislocations in streptomyces? (author's transl)]. PMID- 6258214 TI - [Cerebral and spinal cord glioma in the same individual multiple or multicentric?]. AB - The problem of multiple primary gliomas is discussed starting from a personal report concerning with a case of coexisting cerebral and intramedullary gliomas. Pathological examination allows the Authors to differentiate the cerebral from the medullary tumor by means of the principles of the new WHO classification of brain tumors. In this way it is possible to support the hypothesis of multicentricity. In diagnosing multiple or multifocal tumors the clinical criteria are preferred to the pathological observations. It is felt that in this way a more correct diagnostic and therapeutic approach to the multicentric tumors may yield good results. The theoretical basis for multicentric growth conclude the work. PMID- 6258215 TI - [Effect of nitrogen/fertilizers on the nitrate and nitrite contents of carrots, lettuce and spinach]. PMID- 6258216 TI - [Effect of ionic composition of the medium on the cytochrome oxidase of brain of rats of different age (author's transl)]. PMID- 6258217 TI - Effect of repeated application of ACTH on exploratory activity, brain monoamines, plasma biochemistry and organ alterations. PMID- 6258218 TI - All cis-5, 8, 11, 14, 17 eicosapentaenoic acid and triene prostaglandins: potential anti-thrombotic agents. PMID- 6258219 TI - Appearance of chemically treated root canal walls in the scanning electron microscope. AB - The dissolving effects of seven endodontic solutions on unprepared root canal walls of young intact human premolars were evaluated with the scanning electron microscope. After incubation at 37 degrees C in distilled water or isotonic saline for 10 min the predentinal surfaces showed no changes as compared with untreated controls. The demineralizers Decal and Largal Ultra had little effect on the organic tissues but caused some decalcification where mineralized dentin was exposed. Nelex caused concentration-dependent coagulation of the residual pulp tissue, making typical ring structures on the surfaces. Sodium hypochlorite at 2.5% and 5.0% dissolved most of the predentin, exposing the globular appearance of the mineralizing front. Salvizol produced small globules on otherwise intact surfaces. Dissolution of both the organic and inorganic tissue of the root canal wall would require the combined use of two of the solutions studied. PMID- 6258220 TI - Dissolution of bovine pulp tissue by endodontic solutions. AB - Pulpal tissue was incubated at 37 degrees C for 10 min with various solutions used for root canal therapy. The dissolved material was assayed for hydroxyproline (HYP) and total phosphate, and the insoluble residue for HYP and dry weight. Sodium hypochlorite (NaOCl) at 5% and diluted to 2.5% showed the strongest solvent capacity measured as loss of HYP and weight from the tissue. Dilution to 0.5% significantly decreased the effectiveness of NaOCl. The absence of HYP from the NaOCl extracts suggested decomposition of this amino acid. The other solutions tested were far inferior in their ability to dissolve pulpal tissue. The demineralizing solutions tested were poor solubilizers of soft tissue; however, they caused a considerable increase in the amount of phosphate released. PMID- 6258221 TI - Production of human IgM anti-D in tissue culture by EB-virus-transformed lymphocytes. AB - Lymphocytes obtained from two donors who were producing anti-D were transformed with Epstein-Barr virus and grown in tissue culture. The lymphoblasts from both donors produced anti-D antibody, which agglutinated Rh-positive cells in saline. Both antibodies belonged to the IgM class; the concentration of anti-D in the culture fluid from one of the donors was approximately 250--500 ng/ml and bound firmly to Rh-positive cells with a functional affinity constant of approximately 1 x 10(9) M-1. PMID- 6258222 TI - Dynamics of the interaction between Entamoeba histolytica and components of the immune response. AB - Trophozoites of Entamoeba histolytica redistributed specific antibodies reacting to antigens on their surface. The presence of a second layer of anti-antibodies enhanced the redistribution of anti-amoeba antibodies but was not a prerequisite for this process. Microfluorometric measurements of the fluorescence intensity in different areas of the cell surface provided objective evidence for the antibody induced redistribution. In order to distinguish surface-bound and internalized anti-amoeba antibodies, the trophozoites were fixed in PFA. This fixation made the cells impermeable to antibodies. Thus, after fixation in PFA at different times during the redistribution process surface-bound anti-amoeba antibodies labelled with one fluorochrome could be detected with anti-bodies labelled with another fluorochrome. This approach showed that the amoeba, in addition to the redistribution, also internalized anti-amoeba antibodies. PMID- 6258223 TI - [Detection of IBR/IPV antibodies in milk]. PMID- 6258224 TI - [Rota- and coronaviruses associated with neonatal calf diarrhea: identification of viruses by immunoelectron microscopy, histological and clinical studies]. PMID- 6258225 TI - Electrochemical reduction of horse heart ferricytochrome c at chemically derivatized electrodes. AB - Platinum or gold electrodes derivatized with an N,N'-dialkyl-4,4'-bipyridinium reagent can be used to reduce horse heart ferricytochrome c, whereas reduction doses does not occur at the "naked" electrodes. From 3 to 17.7 millimoles per liter, the reduction of ferricytochrome c is mass transport-limited at electrode potentials more negative than about -0.6 volt against a saturated calomel reference electrode. Data for the photoreduction of ferricytochrome c at derivatized p-type silicon photocathodes show directly that the rate of reduction is mass transport-limited. Use of derivatized electrodes may allow convenient manipulation and analysis of biological molecules that do not ordinarily respond at conventional electrodes. PMID- 6258226 TI - Receptor for albumin on the liver cell surface may mediate uptake of fatty acids and other albumin-bound substances. AB - Kinetic analysis of the uptake of carbon-14-labeled oleate in a single-pass perfusion of rat liver and saturable and specific binding of iodine-125-labeled albumin to hepatocytes in suspension suggest the existence of a receptor for albumin on the liver cell surface. The putative receptor appears to mediate uptake of albumin-bound fatty acids by the cell and may account for the efficient hepatic extraction of many other substances tightly bound to albumin. PMID- 6258227 TI - Opiate receptor gradients in monkey cerebral cortex: correspondence with sensory processing hierarchies. AB - In order to obtain information on the possible functions of endogenous opiates in the primate cerebral cortex, we assessed the distribution of mu-like opiate receptors (which selectively bind 3H-labeled naloxone) and delta-like opiate receptors (which selectively bind 3H-labeled D-Ala2, D-Leu5-enkephalin) throughout the cerebral cortex of the rhesus monkey. Stereospecific [3H]naloxone binding sites increased in a gradient along hierarchically organized cortical systems that sequentially process modality-specific sensory information of a progressively more complex nature. Specific [3H]enkephalin binding sites, in contrast, were relatively evenly distributed throughout the cerebral cortex. These results, in combination with electrophysiological studies of monkeys and humans, suggest that mu-like opiate receptors may play a role in the affective filtering of sensory stimuli at the cortical level, that is, in emotion-induced selective attention. PMID- 6258228 TI - Growth factors modulate gonadotropin receptor induction in granulosa cell cultures. AB - Epidermal growth factor and fibroblast growth factor inhibited follicle stimulating hormone-dependent induction of luteinizing hormone receptor in cultured ovarian granulosa cells of the rat. In contrast, platelet-derived growth factor potentiated the induction of luteinizing hormone receptor by follicle stimulating hormone. These results indicate that growth factors, well known for their effects on mitosis and DNA synthesis in cultured mammalian cells, are also able to modulate hormone-dependent differentiation in an endocrine target cell. PMID- 6258229 TI - Imipramine: effect of ovarian steroids on modifications in serotonin receptor binding. AB - Long-term administration of imipramine caused a decrease in serotonin2 receptor binding in rat brain cerebral cortex, an effect that was abolished by ovariectomy. In contrast, ovariectomy had no effect on imipramine-induced decreases in hippocampal serotonin or in cerebral cortical and hippocampal beta adrenergic receptor binding. Administration of estradiol or progesterone separately or in combination reestablished the effect of imipramine treatment on cortical serotonin2 receptors. These results suggest that ovarian steroids may play an important, but subtle, role in the neurochemical and perhaps clinical response to this drug. PMID- 6258230 TI - Pentobarbital: dual actions to increase brain benzodiazepine receptor affinity. AB - The binding of [3H]diazepam to benzodiazepine receptors was studied in extensively washed membranes of rat cerebral cortex in the presence of the depressant barbiturate, pentobarbital. Pentobarbital, like the endogenous neurotransmitter gamma-aminobutyric acid (GABA), increased the basal binding and also potentiated the GABA-enhanced binding of [3H]diazepam to benzodiazepine receptors by increasing the apparent affinity of [3H]diazepam for the benzodiazepine receptor. The concentrations of pentobarbital necessary to elicit these effects in vitro are the same as those observed after treatment with pharmacologically relevant doses, suggesting that a common neurochemical association may exist between these types of compounds. PMID- 6258231 TI - [One hundred and twenty-three cases of sickle-cell trait (author's transl)]. AB - One hundred and twenty-three cases of sickle-cell trait (122 negro immigrants) are studied in a department of internal medicine. The frequencies of G6PD deficiency, anemia, splenomegaly and tuberculosis are neighbouring at the negro without hemoglobinopathy. The relationship between the sickle-cell trait and the reason of admission of the final diagnosis il likely in 2,4 % of the cases, doubtfully in 15,4 %, null in the other cases. The occasional (hemolytic, thrombotic, painful, visceral, osseous) manifestations of the sickle-cell trait (apart from the constant hyposthenuria) and their mechanism are summarized and discussed. PMID- 6258232 TI - [Osseous manifestations and hemoglobinopathies C (author's transl)]. AB - The authors report two cases of hemoglobin C trait and hemoglobin C disease with bone tuberculosis and, in the first case, bone infarction of one condyle two years after the tuberculosis of the other knee. This suggests the possibility of osseous manifestations in the course of hemoglobin C trait or hemoglobin C disease apart from hemoglobin SC disease. PMID- 6258233 TI - [Osseous manifestations of treponematoses : six cases in immigrated black African (author's transl)]. AB - The authors report the cases of six immigrated Black Africans with clinical and radiological (4 cases with condensing osteitis ; 2 cases with condensing forms and multiple lacunae) bone manifestations ; these manifestations, the serological tests and the osseous biopsy (three cases out of four) are consistent with the diagnosis of bone syphilis. These facts are discussed and ascribed to tertiary syphilis rather than to congenital or secondary syphilis, to yaws or endemic syphilis. PMID- 6258234 TI - [Granulomas of the liver : a clinical and pathological study of fifty-five cases (author's transl)]. AB - After a clinical and pathological study of 55 cases of granulomatous hepatitis, the authors are trying to understand the data so that they can predict the etiology of the granulomas. The authors must insist on the necessity of homogeneity in clinical data, histological findings and ethnic origins. PMID- 6258235 TI - [Surface membrane in skeletal muscle : current biochemical approach (author's transl)]. AB - Three kinds of membranes were found to be present in the skeletal muscle : the plasma membrane, the T-System membrane and the Sarcoplasmic Reticulum membrane. Although they are in continuity, they have quite different properties. Isolation of Sarcoplasmic Reticulum membrane is technically easy. On the other hand, the plasma and T-System membrane isolation has been found to be more difficult. The various methods of purification of these last two components of the muscle fiber are reviewed as well as the biochemical markers allowing their characterization. PMID- 6258236 TI - [Hereditary microcephaly with autosomal dominant chorioretinal dysplasia (author's transl)]. AB - Within the heterogeneous group of microcephalies, a syndrome can be defined characterized by microcephaly, mental retardation, and chorioretinal dysplasia, often also with microphtalmia and embryonic remnants such as persistance of the primitive vitreum. Although this condition is usually considered autosomal recessive, the authors report a family observation consistent with dominant transmission. PMID- 6258237 TI - [Comparative trial between two drugs in the treatment of vomiting induced by anti cancer chemotherapy (author's transl)]. AB - In order to prevent vomiting induced by anti-cancer chemotherapy, the efficiency of domperidone has been compared to metoclopramide in a randomised trial. No difference has been observed between both emetic treatments. PMID- 6258239 TI - [Neurogenic endothoracic tumours (author's transl)]. AB - 123 nervous thoracic tumours have been operated without immediate postoperative death. From 1964, 86 are the subject of a new study. 80 % were situated in the posterior gutter and were involving the sympathetic chain and intercostal-nerves. 20 % have an ectopic parietal, lateral, mediastinal or pulmonary site. 95 % are benign tumours, of which 59 % are schwannomas, 20 % neuro-fibromas, 17 % ganglio neuromas. The conditions of their excision are discussed particularly relating to stud collar tumours which have an extension in or towards the intervertebral foramen, as well as endo-thoracic Recklinghausen tumours, numbering seven. The two patients operated of malignant tumours (schwanno-sarcomas) died of recurrency within 18 months. PMID- 6258238 TI - [152 cases of tuberculosis in African Negro immigrants in a Parisian service of internal medicine (author's transl)]. AB - This study of 152 cases of tuberculosis in African Negro immigrants seen between 1972 and 1976 showed the predominance of especially pulmonary respiratory lesions and/or hilar ganglio-mediastinal lesions. The other lesions are frequent, i.e. the lesions of lymph nodes, bones, peritoneum, liver, pericardium ; the multiple lesions are likewise frequent. Smears and culture of sputum and/or biopsy of organs or tissues such as pleura, lymph node, liver and peritoneum are the diagnostic procedures. In spite of frequent resistance, treatment with isoniazid, rifampicin and ethambutol gave good results in high risk subjects, who are almost always allergic on arrival in France. PMID- 6258240 TI - [Erythrocyte phospholipids in Duchenne muscular dystrophy (author's transl)]. AB - The different fractions of erythrocyte phospholipids determined in eleven patients suffering from Duchenne muscular dystrophy and in six possible or probable heterozygous carriers do not differ significantly from those observed in controls. Distribution of their fatty acids shows a reduced amount of palmitoleic acid (C16 : 1) in total fatty acids, in sphingomyelin and phosphatidylethanolamine. The same anomaly is observed, but less significant, in the heterozygous carriers. The C20 : 0 acid is increased in sphingomyelin. Some overlap occurs between results determined in hemizygous or in heterozygous carriers and in controls. These anomalies in fatty acid distribution, if confirmed, may help a better understanding of the pathogenesis of the disease and perhaps be useful to its detection. PMID- 6258241 TI - [Mega-ureter, mega-bladder and familial diabetes insipidus (author's transl)]. AB - The authors relate a case of bilateral mega-ureter with mega-bladder caused by familial diabetes insipidus. Its treatment with ADH substances like gave a normal diuresis and a very important improvement in bilateral urinary tract distension. PMID- 6258242 TI - [Idiopathic exudative gastroenteropathy with apparently spontaneous recovery : a case report (author's transl)]. AB - The sudden occurrence of oedemas of inferior limbs in a 36 years old woman, has been ascribed to a severe hypoalbuminemia consecutive to an exudative gastroenteropathy of which etiology remained unknown. A successful and lasting evolution followed the correction of hypoalbuminemia by albumin perfusions in exclusion of any other therapy. Such observations though frequent in the childhood are exceptional at maturity. PMID- 6258243 TI - [IgM multiple myeloma (author's transl)]. AB - A new case of IgM myeloma in a 47-year-old man is reported. Multiple myeloma was diagnosed by serum electrophoresis and immunoelectrophoresis, marrow plasmocytosis and typical skeletal changes by X - Ray the synthesis of the M - component was demonstrated in the plasma cells of the bone marrow by direct immunofluorescence study. A review of literature was done and relation between macroglobulinemia of Waldenstrom and IgM myeloma was discussed. PMID- 6258244 TI - [Precocious puberty due to HCG secreting pinealoma (author's transl)]. AB - The present report concerns a six years nine months old boy in whom a HCG secreting pineal tumor (pinealocytoma type I) was responsible for precocious puberty. Features : polydipsia, deepened voice, pubic hair, penile enlargement without corresponding testicular growth. Serum basal concentrations of LH (150 mU/ml), testosterone (85.80 nanomole/l), HCG (115 ng/ml) and its beta subunit (15 ng/ml) were markedly elevated, FSH was low (3.9 mU/ml) ] dissociated hypopituitarism was also present. A surgical removal of the tumor was performed (RIA of the neoplastic tissue revealed high HCG and beta HCG activity) and after the operation the child had radiation therapy. Recovery for the foregoing procedure was rapid, but after some months, in spite chemotherapy his condition deteriorated progressively. The apparent limitation of pinealoma and precocious puberty to the male sex is discussed and supposed to be partly the result of the ectopic gonadotropin secretion. These tumors are compared to other HCG secreting carcinomas located elsewhere in the body and causing sexual precocity in boys only. PMID- 6258245 TI - [Anterior sacral meningocele. A report of one case demonstrated by tomo-scan (author's transl)]. AB - The account of an anterior sacral meningocele, the clinical manifestation of which were cephalagia and urinary disorders. Radiologically, apart from partial agenesia of the terminal sacral segments, an IVU showed a crossed renal ectopia with horse-shoe kidney and a spectacular vesical displacement caused by extrinsic compression. The tomo-scan brought into evidence a voluminous, spreading pelvic processus attached to the spinal canal through a hiatus in the neuro-sacral arch. Clinically, semeiology was primarily a matter of the local effects caused by displacement of the abdomino-pelvic organs ; secondarily it concerned the neurological disorders resulting from compression of the nerve roots included in the cystic wall. As well as the "scimitar" appearance of the sacrum-considered to be pathognomonic - the radiological triad comprises a visualization of the communication between the spinal canal and the kystic pouch - obtained by myelography, preferably gaseous, in association with tomography, and lastly a demonstration by tomo-scan of the hiatus in the neuro-sacral arch. A trans-sacral surgical approach with elimination of the kyst by means of closing off the neck without total excision of the pouch is the most indicated treatment. PMID- 6258246 TI - [Fabry's disease without cutaneous angiokeratoma : diagnosis by electron microscope study of skin biopsy (author's transl)]. AB - A case of Fabry's disease without typical skin lesion is reported. Electron microscope study of normally appearing skin (at clinical and even histological levels) has shown typical inclusions within cytoplasm of various dermic cells (endothelial cells and pericytes, myocytes, fibroblasts) and adipocytes. These inclusions are made up of stacks of membranes with parallel array and periodicity about 5 nanometers. Such a case emphasizes usefulness of electron microscopy of skin, even normally appearing, for the diagnosis of Fabry disease, as it has been previously shown for other dyslipidoses. PMID- 6258247 TI - [Recent data on the pathophysiology of acute tubular nephritis (author's transl)]. PMID- 6258248 TI - [Epidemiology of depressive states and the vulnerability of women to depression]. PMID- 6258249 TI - Breast cancer controversies: surgical decisions. PMID- 6258250 TI - [A study on the phosphatase activities of Bacterionema matruchotii (author's transl)]. PMID- 6258251 TI - Pulmonary infiltrates in a compromised host. PMID- 6258252 TI - Herpes encephalitis after infectious mononucleosis. PMID- 6258253 TI - Relapsing polyneuritis and respiratory failure. PMID- 6258254 TI - [The Alius-Grignaschi anomaly: assessment of granulocyte function and lysosomal enzymes (author's transl)]. PMID- 6258255 TI - Treatment of early cancer of the breast (T1N0M0 and T2N0M0) on the basis of histologic characteristics. AB - This is a retrospective study of the results of various types of surgical treatment of early breast cancer staged histologically using the following characteristics: (1) poor cytologic differentiation, (2) lymphatic permeation, (3) blood vessel invasion, or (4) invasion of the tumor into the surrounding soft tissue. Four hundred and three patients who had early tumors of the breast--228 T1N0M0 (tumor 2 cm or less in diameter, no nodal involvement, and no metastasis) and 175 T2N0M0 (tumor 2 to 5 cm in diameter, no nodal involvement, and no metastasis)--were treated at St. Vincent's Hospital and Medical Center between January 1, 1965, and December 31 1976. Eighty-three were classified as being at low risk 190 at intermediate risk, and 130 at high risk. At 10 years, 100% of the low-risk group were alive; 99% were free of disease, and any type of mastectomy performed--radical, modified radical, or total--was adequate. At 10 years, 44% of those at high risk were alive, and 30% were free of disease. Radiotherapy improved life expectancy when added to radical mastectomy in the high-risk group. We recommend a prior excisional biopsy for proper histologic evaluation to allow a more appropriate choice of surgical procedure. PMID- 6258256 TI - Opiate receptors and endorphins in the pathophysiology of hemorrhagic shock. AB - We investigated the hypothesis that endorphins released by stress act on opiate receptors to depress cardiovascular function during hemorrhagic shock. Anesthetized adult mongrel dogs were bled into a heparinized reservoir to achieve a mean arterial pressure (MAP) of 45 mm Hg. The reservoir was adjusted to maintain MAP for 1 hour and then clamped for 1 hour, at the end of which time the shed blood was reinfused. While the reservoir was clamped we treated the animals with an intravenous bolus followed by 3-hour infusion of either 0.9% NaCl (as control) or the specific opiate receptor antagonist naloxone at three dose regimens (0.5, 1, or 2 mg/kg plus 0.5, 1, or 2 mg/kg . hr). Naloxone produced dose-dependent increases in MAP, cardiac output, stroke volume, and left ventricular contractility. Survival at 72 hours was related to the dose of naloxone used. None of six dogs treated at 0 mg/kg . hr survived, one of six survived at 0.5 mg/kg . hr, four of five at 1 mg/kg . hr, and five of five at 2 mg/kg . hr. Since naloxone has minimal effect on cardiovascular function in nonshocked dogs, these results implicate opiate receptors and perhaps endorphins in the cardiovascular pathophysiology of hemorrhagic shock. PMID- 6258258 TI - [Magic in human thought. Its effect on medicine]. PMID- 6258257 TI - [Effect of parathyroid hormone and thyrocalcitonin on various pathogenetic mechanisms of duodenal ulcer]. PMID- 6258259 TI - [With the scalpels of gene surgery against disease and hunger]. PMID- 6258260 TI - What is the best treatment for early operable small cell carcinoma of the bronchus? PMID- 6258261 TI - Radiographic, scintigraphic, and gas-dilution estimates of individual lung and lobar volumes in man. AB - We describe a method of separately determining the volumes of the right and left lungs from conventional chest radiographs and of determining the volumes of individual lobes and pathological spaces, whenever their boundaries are visible radiologically or can be displayed scintigraphically--for example, during fibreoptic bronchoscopy. Scintigrams of individual lungs, lobes, and segments are obtained by deflecting a stream of air marked with 81m krypton down the suction channel of the bronchoscope into the appropriate bronchus during inspiration, followed by a breath-hold during which the image is recorded with a gamma camera. Both radiographic and scintigraphic methods have been validated by comparison with argon dilution estimates of individual lung and lobar volumes also obtained at bronchoscopy, and results for the three methods in normal subjects are presented. Used in conjunction with bronchoscopic soluble gas uptake studies, these volume measurements permit precise estimation of effective perfusion, tissue and water volume, and gas transfer at lobar and segmental level. Individual lung and lobar volumes can be used to quantify lung and lobar collapse and compression, mediastinal shift, regional ventilation and gas trapping, and phrenic paresis. PMID- 6258262 TI - A biphasic effect of prostacyclin (PGI2) on platelet aggregation. PMID- 6258263 TI - [Polyneuropathy induced by disulfiram]. PMID- 6258264 TI - Pattern analysis of chronic liver diseases from the viewpoint of structural connectivity. AB - On microscopic picture of cirrhosis and allied disorders, "degree of nodular separation" rho theta was established to measure the advancement of cirrhotic change. Based on mathematical treatment of the curvature of linear boundaries between the parenchymal and interstitial areas, rho theta is defined as: rho theta = theta A (net)/theta A (abs) (-1 smaller than or equal to rho theta smaller than or equal to +1) where theta A (net) is the net sum and theta A (abs) the absolute sum of the angles subtended by the boundaries in an area A, provided that plus and minus angles are distinguished according to whether the curvature is convex or concave toward the interstitium. rho theta = +1 when all nodules are round and completely separated, and diminishes with advancing internodular coalescence, finally to a negative value when the interstitium is disconnected to separate parts by nodular joining. The parameter thus describes patterns of different connectivity, serving as a measure of architectural disorganization. rho theta is easily determined by tangent counting on histological picture. The method was applied to 70 autopsy cases including cirrhosis and chronic hepatitis, and the results were related to the hepatic weight, development of hepatoma, and so on. PMID- 6258265 TI - 99mTc-PI as safe and easy scintigraphy after hepatectomy. AB - Hepatobiliary scintigraphy with 99mTc-PI was performed on 16 patients after various types of hepatectomy for either primary or secondary liver tumor. 99mTc PI scintigraphy was found very useful, especially in regard to clinical evaluation of indistinct low-uptake areas observed on a 99mTc colloid liver scintigram in the regenerating liver after hepatectomy. Both tests were conducted successively within a couple of weeks. Colloid scintigrams after hepatectomy were divided into two groups according to the sites of indistinct low-uptake areas; one showed them near the resected margin of the regenerating liver (Type I), and the other showed them in both marginal and intrahepatic. regions (Type II). Of these 16 patients, 8 showed Type I and 7 showed Type II. The remaining one was excluded for postsurgical complications. By comparing the colloid scintigram with the 99mTc-PI scintigram, in all the cases of Type I indistinct low-uptake areas were found to be the hilum with a shifted common bile duct. On the other hand, in 2 cases of Type II indistinct low-uptake areas were caused by the hilum accompanied by the dilated bile ducts. In the remaining 5, indistinct low-uptake areas were not identified as bile ducts but were confirmed to be a recurrence of the tumor. PMID- 6258266 TI - Effect of ethanol treatment on high molecular weight phosphoprotein phosphatases of rat liver. AB - When the crude phosphoprotein phosphatase fraction of rat liver cytosol was treated with 80% aqueous ethanol at room temperature, the activity with phosphorylase alpha as substrate was increased by 110%, but those with glycogen synthase D and phosphohistone were decreased by 53 and 34%, respectively. Chromatography of the ethanol-treated fraction on DE-52 revealed that while phosphoprotein phosphatase IA (Mr=69,000) remained to exist even though it was reduced, phosphatases IB (Mr=-300,00) and II (Mr=160,000) were totally replaced by a new phosphatase form with an approximate molecular weight of 35,000. This low molecular weight form has been designated phosphatase III. When partially purified phosphatases IB and II were separately treated with ethanol, they were converted to phosphatase III. These results suggest that phosphoprotein phosphatases IB and II, but IA, contain phosphatase III as a subunit. Phosphatases IB and II, however, must differ in structure since "IB to III" is accompanied by an increase in phosphorylase phosphatase activity much greater than that for "II to III" PMID- 6258267 TI - Inhibition of prolyl hydroxylase activity in the aorta of rats by propranolol in vitro. AB - The enzyme of prolyl hydroxylase was prepared from the rat aorta. The prolyl hydroxylase activity was measured by the tritium release assay in vitro. Propranolol at concentrations of 3 X 10(-6)M, 10(-5)M inhibited the prolyl hydroxylase activity by 20.6%, 69.8% and 93.7% of control activity, respectively, when the reaction mixtures were incubated for 30 min. It is suggested that propranolol may exert some influence on the collagen biosynthesis of the blood vessels. PMID- 6258268 TI - Endocrinological, neurochemical, and anabolic effects of polybrominated biphenyls in male and female rats. PMID- 6258269 TI - Some enzyme and hormonal attributes of hepatoma cell membranes. AB - Adenylate cyclase activity was measured in plasma membranes isolated form Morris Hepatomas (44 and 47C) and from their host livers. We found that the enzyme activity in the tumours was very low, approx. 5% of the level in control and host livers. The amount of cAMP and cGMP in the tumours was also lower than in the host livers but the ratio of cGMP to cAMP in the tumours was increased by a factor of 4-5. The membrane binding capacities for the pancreatic hormones insulin and glucagon were measured. Hepatoma membranes bound less glucagon than those of livers. A decrease in the number of the glucagon receptors was found but there were no changes in the affinity constant. For insulin, we found the same binding capacity as the host and control livers; thus there was an increase in the ratio of insulin bound/glucagon bound in tumours as compared to controls. The plasma levels of insulin in the tumour bearing animals were approximately half of those in control, whereas the glucagon levels in plasma were 60-62% higher in tumour bearing animals. These results are discussed in terms of the characterization of normal, foetal and regenerating liver, in comparison with slow growing hepatomas. The levels of cAMP and cGMP are discussed with respect to control mechanisms of cell proliferation. PMID- 6258270 TI - Detection of delta-9-tetrahydrocannabinol in the organs of a suspected case of cannabis poisoning. AB - An unusual case of fatal poisoning by delta-9-tetrahydrocannabinol (delta-9-THC)- a physiologically active constituent of cannabis--is reported. Methods of isolation and detection of delta-9-THC was estimated quantitatively by thin-layer chromatography (TLC) and photoelectric densitometry. PMID- 6258271 TI - [Investigations with beagles about toxicity and radioprotective effect of the clinical radioprotection substance WR 2721. Part I. Toxicity of WR 2721 (author's transl)]. AB - The toxicity of the chemical radioprotection substance WR 2721 (S-2-(3 aminopropylamino)ethyl-thiophosphate) was examined in 25 beagles. The study showed that the toxicity of the substance increases as the dose gets higher. Between the doses 200 and 250 mg/kg of body weight, the increase of toxicity was significantly greater than could be expected on the basis of the dose difference. Until a dose of 200 mg/kg, the authors found no side effects which would have disturbed vital functions, but higher doses led to marked symptoms of intoxication. PMID- 6258272 TI - Administration of DTC gives evidence of a role of the thymus in the control and regulation of factors inducing thymocyte differentiation in the mouse. AB - Nude (B6) mice, grafted with a syngeneic thymus, are treated 3 wk later with 25 mg/kg of sodium diethyldithiocarbamate (DTC). Serum sampled 24 h afterwards is heated at 56 degrees C for 45 min and tested over a large range of doses for its in vitro capacity to induce Thy-1+ cells in nu/nu spleen cells. Data are compared with the effects of DTC on ungrafted nude mice, and on B6 and C3 mice. Each group comprised 5 to 6 animals. The thymus of B6 mouse abrogates the action of DTC to induce in thymus-less mice two serum factors, active at different concentrations. The serum of DTC-treated C3 mice has an increased T-cell recruiting activity in contrast with the serum of DTC-treated B6 mice. The findings are interpreted as evidencing the extra-thymic origin of one active factor, and a role for the thymus to regulate the synthesis of both factors. PMID- 6258273 TI - The human thymus. I. Partial characterization of nonlymphoid cells. AB - Human thymus was disrupted by mechanical and enzymatic techniques yielding tissue fragments and single-cell suspensions. Cell types and their distribution were determined before and after density separation. Single-cell suspensions produced by both separation procedures yielded comparable percentages of lymphoid and monocytic cells, whereas only the enzyme-treated tissue yielded epithelial cells. Less than 1% of all monocytic cells were mature. Monolayer cultures were established from fragments as well as unfractionated cells and gradient fractions. Analysis of these cultures showed that: (1) gradient separation of mechanically-prepared cell suspensions produced cultures enriched for macrophages, while epithelial cell cultures could be produced from fractionated enzyme treated tissue; (2) spindle-shaped cells may be fibroblasts or epithelial cells; (3) explant cultures have a growth pattern characteristic of other epithelial cells in vitro; (4) macrophages constitute a definite population of explanted cells and their percentages increase with time in culture; (5) macromolecular synthesis by epithelial cells in culture may be donor age dependent. Nonlymphoid cells of the human thymus can be identified by a variety of separation techniques and after monolayer culture. Characteristics of these cells are defined which may affect cell-cell interaction studies of the thymus. PMID- 6258274 TI - Cytomegalovirus as a risk factor in renal transplantation. AB - A prospective study of 276 patients that were greater than 12 years old and received transplants between October 1, 1977 and September 30, 1979 has been undertaken. Any patient with clinical findings compatible with overt cytomegalovirus (CMV) disease was placed on a "CMV disease diagnostic protocol." All diagnosed cases of CMV occurring before November 15, 1979 have been analyzed. Eighty patients (29%) had overt CMV disease. Seventy-two (90%) of them contracted CMV within the first 3 months post-transplant. The incidence of overt CMV varied with donor type. Eight percent (4 of 49), 17% (8 of 48), 20% (5 of 25), 40% (46 of 115) and 43% (15 of 35) of HLA-identical (ID) siblings, non-ID siblings, child donor, cadaveric donor, and parental donor, respectively, contracted CMV disease. Overt clinical CMV disease influenced the graft function and patient survival rates significantly (P < 0.01). Several risk factors have been considered as possible indicators of CMV disease. These include age, sex, diabetic status, time of onset of CMV, donor and recipient CMV complement-fixing (CF) and indirect fluorescence (IF) titers. The same variables were analyzed to determine whether they might also predict the severity of the disease. Donor CF is the single most important risk factor. Recipient serology alone was not found to be a significant risk factor but 15 of 27 (56%) persons who had a negative titer and received a kidney from a donor with a positive CF titer contracted overt CMV. Nine of those 15 (60%) had moderate, severe, or lethal illness. PMID- 6258275 TI - [Fever of unknown origin. Case report]. PMID- 6258276 TI - [Muscarinic regulation of cyclic GMP levels and catecholamine secretions in chromaffin cells]. PMID- 6258277 TI - [Modification of the hypertensive effect of beta-endorphin by the adrenal glands]. PMID- 6258278 TI - [Nonepithelial tumors of the stomach]. AB - The authors recommend a clinico-histological classification of nonepithelial tumors of the stomach which allows the clinical course of the tumor to be foreseen and, chiefly, gives orientation concerning the value of operation and the additional treatment with special reference to remote results. PMID- 6258279 TI - Glucocorticoids: their use and misuse in veterinary practice. PMID- 6258280 TI - [Isolation of cytopathogenic strains of infectious bursal virus of chickens in cell cultures]. AB - Five virus strains with cytopathogenic properties for the cell cultures of chick embryo fibroblasts and embryo kidney cells were isolated from chickens clinically suspected of suffering from infectious bursitis. According to the form of cytopathic effect (CPE) on cell cultures, according to chloroform and thermal resistance, nature of nucleic acid (RNA), according to the absence of the production of intracellular inclusions, negative haemagglutination, and according to antigenic identity with the reference strain, the isolates were deemed to belong to the viruses of infectious bursitis. This conclusion was also corroborated by histological and serological studies in isolates of infected experimental animals. PMID- 6258281 TI - Acidophil adenoma in the pituitary gland of a sheep. PMID- 6258282 TI - Liquoid-induced renal lesions in the dog. AB - The role of fibrin in the pathogenesis of renal glomerular scarring in the dog was studied. Fibrin deposition, resulting from disseminated intravascular coagulation, was induced by intravenous injection of Liquoid (sodium polyanethol sulphonate). Thirty-eight puppies were killed from 30 minutes to 39 days after treatment, and the renal lesions examined by light, electron and immunofluorescence microscopy. The major acute lesions in the glomeruli were capillary thrombosis, mesangial and endothelial cell swelling and phagocytosis of fibrin, polymorphonuclear leukocyte infiltration and necrosis. Animals that recovered from this acute phase had focal glomerular scars. Affected glomeruli showed combinations of mesangial enlargement, focal tuft hypercellularity, collagen formation, thickening, wrinkling and duplication of the glomerular basement membranes, and some capsular adhesions. These observations indicate that fibrin deposition can be an important mechanism in glomerular scarring in the dog. PMID- 6258284 TI - A common code of practice for the control of contagious equine metritis and other equine reproductive diseases for the 1981 covering season in France, Ireland and the United Kingdom. PMID- 6258283 TI - Induction of retinal degeneration in cats by methylnitrosourea and ketamine hydrochloride. AB - Persistent mydriasis seen in cats used in an oncology study apparently was not related to neoplasia. Ophthalmoscopically, the cats had severely atrophic retinas and clinically observable visual impairment. These findings were confirmed by electroretinographic and histologic examination. Cats with these retinal lesions had received combinations of methylnitrosourea, ketamine hydrochloride, and feline leukemia virus. Retinopathy was not seen in ketamine-anesthetized cats receiving feline leukemia virus. To test the nature of this phenomenon, four cats were given both drugs and three received methylnitrosourea alone. The four cats developed severe generalized retinal degeneration by day 5, whereas the three cats given methylnitrosourea alone had normal retinas. Histologic changes in the affected cats were extensive loss of rods and cones, and of the outer nuclear layer. The electroretinographic responses to white light were depressed or extinguished. Retinal degeneration, therefore, appeared to be dependent upon administration of both methylnitrosourea and ketamine hydrochloride. PMID- 6258285 TI - Infectious bovine rhinotracheitis virus excretion after vaccination. PMID- 6258286 TI - Detection by electron microscopy of caliciviruses, astroviruses and rotavirus like particles in the faeces of piglets with diarrhoea. PMID- 6258287 TI - Primary signet ring cell carcinoma of the breast. AB - Light microscopic (LM), histochemical, and electron microscopic (EM) investigations of a case of signet ring cell carcinoma (SRC) of the breast indicate that SRC is a variant of mucin-producing carcinoma and that in this particular case, it is of ductal origin. PMID- 6258288 TI - Pancreatic glucagonoma with and without syndrome. Immunocytochemical study of 5 tumour cases and review of the literature. AB - In five patients single or multiple glucagonomas were characterized by immunocytochemistry. Two large single glucagonomas were associated with the glucagonoma syndrome, which completely dissappeared after removal of the tumours. The morphologic findings in these patients are compared with 48 others collected from literature. In the other three patients, the glucagonomas were not associated with a clinical syndrome and were detected by chance (one accompanying an insulinoma; the other in pancreases of patients suffering from multiple endocrine neoplasia I; MEN I). These tumours appeared by their histological, immunocytochemical and ultrastructural features better organized than the glucagonomas with syndrome. Glucagonomas not producing a syndrome can be classified into (a) solitary, often malignant endocrine pancreatic tumours, (b) glucagonomas associated with insulinomas and other tumours, (c) multiple glucagonomas in MEN I and (d) single microglucagonomas in elderly patients. It is emphasized that only immunohistology allows clear identification of these tumours as glucagonomas. PMID- 6258289 TI - Apparent lack of integration of bovine papillomavirus DNA in virus-induced equine and bovine tumor cells and virus-transformed mouse cells. PMID- 6258290 TI - Temporal regulation of the rate of vesicular stomatitis virus mRNA translation during infection of Chinese hamster ovary cells. PMID- 6258291 TI - SV40-transformed cells express SV40 T antigen-related antigens on the cell surface. PMID- 6258292 TI - Filamentous phage DNA cloning vectors: a noninfective mutant with a nonpolar deletion in gene III. PMID- 6258293 TI - Structure of adenovirus chromatin as probed with restriction endonucleases. PMID- 6258294 TI - Molecular variation of type 1 vaccine-related and wild polioviruses during replication in humans. PMID- 6258296 TI - Comparative peptide analysis of avian oncoviral structural protein markers. PMID- 6258295 TI - Isolation and identification of virus-specific mRNAs in cells infected with mouse hepatitis virus (MHV-A59). PMID- 6258297 TI - Restriction endonuclease mapping of ecotropic murine leukemia viral DNAs: size and sequence heterogeneity of the long terminal repeat. PMID- 6258298 TI - The integrated SV40 genome in permissive transformed monkey cells. PMID- 6258299 TI - A cell-determined deficiency in the processing of gag proteins of murine leukemia virus 334C. PMID- 6258300 TI - Envelope proteins of the BALB/c myeloma mink cell focus-inducing (MCF) viruses. PMID- 6258302 TI - Effect of the host cell on the generation of defective Simian Virus 40 during undiluted serial passages and persistent infection. PMID- 6258301 TI - Simian virus 40 induces the production of a polypeptide transforming factor(s). PMID- 6258303 TI - Equine cytomegalovirus: cultural characteristics and properties of viral DNA. PMID- 6258304 TI - Identification of an SV40 DNA sequence related to the reactivation of silent rRNA genes in human greater than mouse hybrid cells. PMID- 6258305 TI - Amino- and carboxyl-terminal sequences of proteins coded by gag gene of endogenous baboon and cat type C viruses. PMID- 6258306 TI - Mutant retrovirus particles package vesicular stomatitis virus mRNA during mixed infection. PMID- 6258307 TI - Polyoma virus recognizes specific sialyligosaccharide receptors on host cells. PMID- 6258308 TI - Avian sarcoma virus PRCII: conditional mutants temperature sensitive in the maintenance of fibroblast transformation. PMID- 6258309 TI - Precursor product relationship between intracytoplasmic A particle and murine mammary tumor virus core proteins established by tryptic peptide analysis. PMID- 6258310 TI - Transformation of 3T3 cells with Abelson virus proviral DNA. PMID- 6258311 TI - Tyrosine-specific protein kinase activity associated with p105 of avian sarcoma virus PRCII. PMID- 6258312 TI - A mutation increasing the size of the polyoma virion proteins, VP2 and VP3. PMID- 6258313 TI - Functions of Sendai virus nucleocapsid polypeptides: enzymatic activities in nucleocapsids following cleavage of polypeptide P by Staphylococcus aureus protease V8. PMID- 6258314 TI - Epstein-Barr virus-induced polypeptides: a comparative study with superinfected Raji, IUdR-Treated, and N-butyrate-treated P3HR-1 cells. PMID- 6258315 TI - Cross-linking of viral RNA by 4'-aminomethyl-4,5',8-trimethylpsoralen in HeLa cells infected with encephalomyocarditis virus and the tsG114 mutant of vesicular stomatitis virus. PMID- 6258316 TI - [Hereditary in the pathology of cell receptors]. PMID- 6258317 TI - [Changes in the activity of cyclic adenosine monophosphate metabolism enzymes in myocardial hypertrophy and after exposure to hyperbaric oxygenation]. AB - Hypertrophy of myocardium, developed within 4 weeks after aorta stenosis, led to alteration in content of adrenaline in heart tissue as well as in some pathways of cAMP turnover: decrease in content of cAMP, an increase in the basal activity of adenylate cyclase, decrease in activation of the enzyme by adrenaline; activity of phosphodiesterase was not distinctly altered. Under conditions of hyperbaric oxygenation hypertrophy of myocardium became less distinct, content of cAMP was increased up to the normal value, the increased basal activity of adenylate cyclase was slightly decreased, whereas sensitivity of the enzyme to adrenaline did not reduce, content of adrenaline was increased. PMID- 6258318 TI - [Isolation of the theta-hemolysin of Cl. perfringens]. AB - Teta-hemolysine was purified from Cl. perfringens strain BP6K 28 as follows: reprecipitation in the isoelectric point of the enzyme with 2 N H2SO4 containing 15% NaCl, DEAE cellulose chromatography, gel filtration on Sephadex G-100-G75 or Bio Gel P-60--P-100, rechromatography on DEAE-Sephadex A-50 and affinity chromatography. The biological activity of homogenous teta-hemolysine, estimated by complete hemolysis of human erythrocytes, exceeded 100, 000 theta E over mg protein but the enzyme was highly labile. Molecular weight of the enzyme was 53,000 daltons. PMID- 6258319 TI - [Effect of adrenaline on cyclic nucleotide concentration in the tissues of rats of different ages]. AB - Content and the ratio of cAMP/cGMP in myocardium, liver tissue and sceletal muscle were similar in adult and old rats. Adrenaline (5 . 10(-6) M) caused more distinct increase in content of cAMP in the old animals. After treatment with NaF (0.01 M) the age differences in the cAMP content were observed only in the heart muscle. Adrenaline appears to activate most effectively adenylate cyclase in tissues of old rats; the enzyme is apparently responsible for enhanced sensitivity to the hormone in senile age. PMID- 6258320 TI - [ACTH-adenylate cyclase in adipose cell "ghosts" of rats with spontaneous hypertension (effect of adrenalectomy)]. AB - Basal, NaF- and ACTH-stimulated activity of adenylate cyclase was studied in "shadows" of fatty cells from intact and adrenalectomized rats with spontaneous hypertension (SHR strain) as compared with the corresponding controls. Activity of ACTH-adenylate cyclase was decreased in control adrenalectomized animals; the enzymatic activity was similar in normal rats, in adrenalectomized animals of the SHR strain and in the intact SHR rats. Basal and NaF-stimulated activities of adenylate cyclase were the same in all the animal groups studied. PMID- 6258321 TI - [Energy formation processes in the myocardium during measured limitation of coronary blood flow]. AB - Effect of short-term partial limitation of coronary circulation (by 30%, 50% and 70%) on energy formation in myocardium was studied in animals with closed thorax after catheterization and autoperfusion of the circumflex branch of left coronary artery. Distinct alterations in energy metabolism were observed already after a decrease of the coronary circulation by 30%. Several enzymes were inhibited in tricarboxylic acid cycle and in respiratory chain following development of ischemia. Despite of the inhibition of the aerobic oxidation content of ATP and glycogen maintained rather stable. Content of ATP was decreased down to 60% of the initial level only after limitation of the circulation by 2/3. Deficiency in aerobic energy production as well as maintaining of a rather stable content of ATP and glycogen were apparently compensated by an increase in cAMP content, activation of glycolysis and pentose phosphate pathway and of adenosine formation. PMID- 6258322 TI - [Participation of cyclic nucleotides in the mechanism of regulation of the tissue pool of coenzyme A and the acetylizing capacity of rats]. AB - cAMP and dibutyryl-cAMP were shown to increase the pool of CoA (or all the pantothenic coenzymes) in rat liver tissue, especially after treatment of the animals with 4-phosphopantothenate but not with pantethine. As shown by experiment with inhibitors of protein synthesis (actinomycin D, actidion, chloramphenicol) immediate c-AMP-dependent stimulation of the biogenesis of pantothenic coenzymes occurred rather from their precursors than due to induction of enzymes, participating in the biogenesis, or to destruction of the pantothenic coenzymes. Experiments with chloramphenicol exhibited that cAMP regulation of the biogenesis of pantothenic coenzymes in mitochondria was responsible mainly for the cellular pool of CoA and, partly, for the acetylation of para-aminobenzoic acid in tissues. PMID- 6258323 TI - [Effect of histones on mouse liver mitochondria cytochrome oxidase activity in vitro and in vivo]. AB - Histones at concentration of 2-10 micrograms/ml activated the mitochondrial cytochrome oxidase and at concentration of 25 micrograms/ml and higher--inhibited the enzyme in vitro. Cytochrome oxidase was completely inactivated by histones at concentration of 100 mg/microliter and higher. After administration in vivo histones modified the reaction of liver mitochondria in response to the subsequent treatment with a non-ion detergent Triton X-100. Possible pathogenetic importance of the phenomena observed is discussed. PMID- 6258324 TI - [Cyclic nucleotides in tissues during long-term hypokinesia]. PMID- 6258325 TI - [Combined treatment of rectal cancer]. AB - In 15 males and 25 females at the age of 24--70 the authors have studied radiation pathomorphosis, the early and late results in anal and low ampullar cancer following preoperative large fractionation irradiation on a gamma therapeutic machine "Rokus" with the rotation regime of 400--600 rad daily, a total dosage--2000--3000 rad. The operation was performed 2--3 days following the irradiation. Eighteen patients were followed up over 3 years. Recurrences and metastases were noted in 5 cases (glandular-solid and mucosa forms of cancer). A 3-year survival was 72.2% versus 40.7% (P less than 0.001) while using surgical therapy solely. PMID- 6258327 TI - [Corticotropin level in peptic ulcer, dumping predisposition and postoperative dumping syndrome]. PMID- 6258326 TI - [Metastatic brain cancer with a remitting course]. PMID- 6258328 TI - The neuropathies of leprosy. PMID- 6258329 TI - [Hypercalcemia in liver tumors (author's transl)]. AB - In 32 patients with primary liver tumors incidence and etiology of hypercalcemia were evaluated. Two patients revealed hypercalcemia from osteolytic metastases, one had coexistent primary hyperparathyroidism and in one patient hypercalcemia was paraneoplastic. The last two patients are presented in detail by case reports. Differential diagnostic problems appear often in patients in bad general condition, since invasive diagnostic methods are limited. The most potent substance to treat acute hypercalcemic syndrome is mithramycin. In those cases where surgical treatment is possible, complete resection of the primary liver tumor or the adenoma of the parathyroid gland is recommended. PMID- 6258330 TI - [Experimental changes of GABA receptor binding in the central nervous system (author's transl)]. AB - The effects of etazolate and cartazolate, two pyrazolopyridine derivatives with anxiolytic actions, on the receptor binding of gamma-aminobutyric acid (GABA) was studied in vitro using membrane fractions prepared from rat brain. Both compounds increased the specific GABA receptor binding. This effect was markedly enhanced in the presence of several anions, predominantly halide ions. Pyrazolopyridines appear to modulate the binding properties of GABA receptors by acting on a site closely related to the chloride ion channel of the membrane. These results indicate that activation of the GABA system is a possible mechanism of action of pyrazolopyridines. In the second part of the study binding experiments were used to provide evidence for the presynaptic localisation of GABA receptors on primary afferent terminals in the dorsal horn of the rat spinal cord. Capsaicin-induced degeneration of primary afferent fibres significantly reduced the number of GABA receptors in the dorsal spinal cord, whereas the number of benzodiazepine and glycine receptors remained unchanged. The results support the role of GABA as transmitter involved in presynaptic inhibition in the spinal cord. PMID- 6258331 TI - [New results in the field of endocrinology with relevance for medical practice. Hyperprolactemia, endocrine adenomatoses, paraneoplastic hormone secretion and hormone therapy of breast carcinoma]. PMID- 6258332 TI - [Statistical evaluation of broncho-pulmonary carcinomas according to the types of the tumours (author's transl)]. AB - Different aspects of broncho-pulmonary carcinomas dependent on the type of the tumours are discussed by means of a statistical analysis. Differences between the types of tumours were found with regard to the frequency in male and female patients, the frequency of the first establishment of diagnosis in the course of the year and the frequency of the formation of metastases in the regional lymphatic nodes. During the last years a change in the frequency-distribution of the different types of tumour has been observed. PMID- 6258333 TI - [Diagnostics in islet cell tumours (author's transl)]. AB - With modern imaging systems like sonography and computer-tomography it is mostly not possible to identify adenomas of the islet-cell-apparatus of the pancreas. These tumours are mostly too small to deform the contours of the pancreas, but because of their intense vascularisation they can be well diagnosed by angiography in form of selective coeliacography, mesentericography or superselective angiography of the pancreatico-duodenal artery. This invasive method is not only necessary to confirm the tentative diagnosis of an adenoma, but also important for its localisation, which is essential for surgery. PMID- 6258334 TI - Epoxide-diol pathway of delta 1-THC in the rat in vitro. AB - 1. 1 alpha, 2 alpha-Epoxyhexahydrocannabinol was identified as a metabolite of delta 1-tetrahydrocannabinol. 2. The two trans-1,2-dihydroxyhexahydrocannabinol isomers, 1 alpha, 2 beta-dihydroxyhexahydrocannabinol and 1 beta, 2 alpha dihydroxyhexahydrocannabinol (as their acetates) were tentatively identified as metabolites from incubation of 1 alpha, 2 alpha-epoxyhexahydrocannabinol with rat hepatic microsomes in vitro. 3. The 1 alpha, 2 alpha-epoxyhexahydrocannabinol acetate was found to be a good substrate for epoxide hydratase as compared to styrene oxide. 4. The synthesis of metabolites of 1 alpha, 2 alpha epoxyhexahydrocannabinol is described. PMID- 6258335 TI - [On the influence of hormones on genome in aging (author's transl)]. AB - The hormonal uptake, binding and responsiveness are decreased with few exceptions in the target organs of old animals. Qualitative changes of chromatin and changed receptor concentration and affinity are considered as causes. PMID- 6258336 TI - [Serum metal content in occupationally HCN-exposed women]. PMID- 6258337 TI - [Examination of enzyme activity in the blood of HCN-exposed women]. PMID- 6258338 TI - Improvement of Supramine and development of new food mixtures for the young. II. Development of new food mixtures for the young. AB - Four high-protein food mixtures for feeding the young were formulated from locally available and relatively cheap legumes and cereals. Protein content of these mixtures ranged from 17.2 to 20.3 g%. Amino acid composition showed agreement with the FAO provisional pattern except for sulphur amino acids. Analysis of the mineral content of the prepared mixtures indicated the necessity of supplementation with zinc and phosphorus to meet the physiological requirements of the consumers. Palatability studies showed that these mixtures are acceptable and with good taste. It is planned to produce these mixtures on an industrial scale after biological and economic evaluation. PMID- 6258339 TI - [Etiologic and epidemiologic study of viral etiology of diarrhea in children]. PMID- 6258340 TI - [Significance of nutrition and diet in diseases of the extrahepatic biliary tract]. AB - On the basis of newer literature and of own experiences the author describes the present state of dietetics in diseases of the extrahepatic biliary ducts. The details of the basic diet in these diseases are discussed (nutrition of patients with limited fat and raw fibre supply). In acute cases the parenteral nutrition is to be recommended. In subacute cases, as well as before and after surgical interventions more frequently ballast-free, fully balanced peroral nutrition (cosmonautes' diet) is used. Finally the importance of the plant raw fibre for the prophylaxis of cholelithiasis is demonstrated. PMID- 6258341 TI - [The problem of multiple malignomas]. AB - It is reported on three female patients who fell ill with a second and third tumour, respectively, within 4 years. The cases in question were spontaneous neoformations, since risk factors, such as radiotherapy and applications of cytostatics were not used causally. PMID- 6258343 TI - [Ketoconazole a new broad spectrum antimycotic]. PMID- 6258342 TI - [The behaviour of endocrinal parameters under prophylaxis of hyaline membrane disease with glucocorticoids (author's transl)]. AB - Prevention of hyaline membrane disease with glucocorticoids produces suppression of the hypopituitary-adrenocortical axis of the mother as well as of the foetus. The extent of the suppression is significantly higher under medication with the 9 alpha-fluorinated preparations, betamethasone and dexamethasone, than under medication with 16-methyleneprednisolone. Increases in the concentration levels of the mineralocorticoid DOC are to be expected in 37% to 50% of the patients, depending on the administered corticoid. The percentage of increase is 150% under 16-methyleneprednisolone and 220% under betamethasone and dexamethasone. PMID- 6258344 TI - [Lymph drainage and edema therapy using physical drainage treatment]. PMID- 6258345 TI - [The MS patient in general practice]. PMID- 6258346 TI - [Self-stimulation reaction in normotensive and hypertensive rats]. AB - The part of noradrenergic mechanisms in self-stimulation (SS) operant behaviour was studied in rats. In all experiments systolic blood pressure (BP) in the tail artery was measured by means of photocells. It was found, that small doses of noradrenaline facilitate the SS, while high doses depress or stop it. The depressive effect is accompanied by a marked increase of BP. Effective blockade of beta-adrenoceptive structures by inderal suppresses SS, and the inhibitory effect is accompanied by a small decrease of BP. Suppressing effect of alpha adrenoblocking agent, phentolamine, is even more pronounced, but is accompanied by a marked decrease of BP. Beta-agonist isadrin causes a marked facilitation of SS without changes of BP. It is suggested that positive reward in the lateral hypothalamus is due to a direct stimulation of beta-adrenoceptive noradrenergic neuronal elements. Chronic neurogenic hypertension is developed by an overloading of the higher nervous activity. In chronic hypertensive rats there is a pronounced suppression of SS. A transient fail of BP caused by injection of catapresan (hemiton) results in a temporary recovery of normal SS behaviour. It may be concluded that reduction of lever-pressing rate during acute and chronic neurogenic hypertensions is related to baroreceptor mechanisms. The role of the autonomic nervous system in SS behaviour is discussed. PMID- 6258347 TI - [Possible mechanisms of the divergent effects of ACTH4--10 and its analog containing the D-isomer of phenylalanine on behavior]. AB - The effect of two oligopeptides--ACTG4-10 and hexopeptide met-glu-his-D-phen-lis L-phen (Dphen-GP) on memorizing the situation and on orienting-investigating reaction was studied in albino rats by the method of elaboration of food procuring habit in T-maze and by the method of "open field". It was shown that these peptides in a dose of 15 mcg/kg with certain periods of administration, have an opposite effect on maze learning but a similar effect on memorizing in the "open field". ACTG4-10 slightly increases motor activity in the "open field", whereas Dphen-GP decreases it considerably. It is suggested that ACTG4-10 improves the formation of trace processes independently of the sign of reinforcement, whereas Dphen-GP selectively enhances defensive reaction and memorizing, connected with negative reinforcement. PMID- 6258348 TI - [Effect of cyclic 3',5'-adenosine monophosphate on central neurons]. AB - In experiments on unanesthetized non-immobilized rabbits, unit responses in the cortex and thalamus to the cyclic 3',5'-adenosine monophosphate (cAMPh) were studied by means of microionophoresis. It was shown that cAMPh changes the pattern of background unit activity, increasing or decreasing the discharge frequency. cAMPh changes unit responses both to acetylcholine and noradrenaline. These data permit, to assume that cAMPh participates both in adrenergic and in acetylocholinergic mechanisms of excitation processing in brain neurones. PMID- 6258349 TI - [Effect of a corticotropin fragment (ACTH5-10) on maze learning in rats reinforced by drinking]. PMID- 6258350 TI - [Use of EC-1020 computers for experimental studies of synaptic interaction of mollusk neurons]. PMID- 6258351 TI - [Investigations on the morphology and biochemistry of wound healing after injury of the liver (author's transl)]. AB - The early phase of wound repair after liver incisions was investigated by histological, enzyme-histochemical, and biochemical methods in guinea pigs. There are considerable differences in cellular and histochemical reactions in comparison to incisions of the skin: 1. The rapid leukocytic reaction showed little change during the observation interval (48 h). In short survival times epithelial cells show signs of hypoxidosis and loss of glycogen at the edge of an incision. Proliferation of organ-specific and mesenchymal cells was observed after more than 24 h. 2. Alterations of the investigated enzymes in the traumatic area are important diagnostic parameters in the early stages of wound healing. 3. In the early 12 h after injury distinct increase of histamine was observed, while serotonin was noticed to decrease. 4. Therefore, the determination of wound age in the early wound reactions after injuries of the liver should include enzymehistochemical methods. PMID- 6258352 TI - [The suitability of bioindicators according to DIN 58948 part 4 for monitoring gas-sterilizers (author's transl)]. AB - In the Federal Republic of Germany bioindicators according to DIN 58948, Part 4, are generally used for testing the efficacy of ethylene oxide sterilizers. They are based on spores of Bacillus subtilis dried in sheep-blood on the bottom of a small test tube. As some authors doubted the resistance of these indicators to ethylene oxide especially in comparison with spore soil and spores of Clostridium perfringens, three different test procedures were performed showing that spores of sulfite reducing clostridia (Cl. perfringens included) are less resistant to ethylene oxide than spores of B. subtilis. The results are summarized in tables 1 to 3. They are discussed with regard to literature on the subject with special emphasis to the significance of occlusion of spores in insoluble crystals. It is concluded that spores of B. subtilis are the most suitable test-organisms for monitoring ethylene oxide sterilization and that spore soil cannot be used for this purpose. PMID- 6258354 TI - [Nuclear-medical testing of retrograde tubal transport mechanism for sterility diagnosis (tubal isotope test TIT) (author's transl)]. AB - Pathological change of the tube is one of the most common causes of female sterility. While mechanical occlusion can be identified by the techniques of tube examination so far in use, tubal function can hardly be assessed by means of them. Described and evaluated in this paper is a test method recently devised in nuclear medicine for the assessment of tubal function. PMID- 6258355 TI - Extracranial spreading of glioblastoma multiforme. AB - On the basis of 4 observations, the formation of extracranial metastases of multiform glioblastomas is dealth with which complied with all the criteria established by Weiss (histological identification of a primary brain tumour, connection of clinical data between cerebral tumour and metastases, ruling out of another primary tumour not belonging to the neuraxis by a complete autopsy). All 4 patients were--in some cases several times--trephined, subjected to postoperative irradiation and some of them were also treated with chemotherapeutics. The postoperative survival time was between 16 and 24 months, the average age of the patients was 35 years which was strikingly low. 3 patients showed infiltrations of bones and neighbouring soft parts, in one case the tumour penetrated into the sinus, in one patient paranasal sinuses and orbitae were affected, two cases showed metastases in the vertebral column and in one case metastases were found in the cervical gland nodes. One glioblastoma accompanied by a fibrosarcoma showed a particularly extensive extracranial formation of metastases. As regards the reasons for the formation of extracranial metastases of intracranial tumors many hypotheses have been established which are critically discussed by the authors. PMID- 6258353 TI - [Adenoid-cystic carcinoma (cylindroma) of Bartholin's gland (author's transl)]. AB - Reported in this paper is a patient with adenoid-cystic carcinoma in the left Bartholin's gland. An account follows of literature on that rare tumour. PMID- 6258357 TI - [Collagenase activity in the ruptured cruciate ligament in dogs and its inhibition in vitro]. PMID- 6258356 TI - [Experience with paraorbital-transethmoidal procedure in pituitary tumors]. AB - In the period from 1977 to 1979, 40 transethmoidal-transphenoidal operations were carried out on 35 patients with hypophyseal adenomas. The patients were subdivided into appropriate groups and showed congruency with other statistics. The transethmoidal procedure permits the shorter anatomical way, can be combined with transnasal instruments and in particular does not involve the later and late consequences of septum operations. The transphenoidal procedure usually is considerably less onerous for the patients than the intracranial subfrontal operation. Indications for the latter are the parasellar hypophyseal tumour and second interventions after insufficient radicality of transphenoidal tumour removal. The handicap in transphenoidal interventions consists in the lacking insight into intra- and suprasellar regions. At present, the X-ray picture intensifier and the subtle intuition of the surgeon are helpful in this connection. For some patients, endocopy of the sella has already been employed. This method, however, still requires further technical improvement, so that tumour remains can also be removed by the endoscopic way. Sometimes, suprasellar tumour parts that have not been removed descend into the sella only in the course of some weeks to some months and can then be removed in a second intervention. Second interventions are also necessary when fistulas appear unless one succeeds already in the tumour operation in closing the surgical opening in the wall of the sella. When no liquorrhoea is present after the removal of the adenoma, the placing of gelatin sponge pieces will be sufficient, otherwise lyophilised dura is glued on the opening. In the postoperative phase, the rapid mobilisation and rehabilitation without any additional psychic phenomena is particularly evident. PMID- 6258358 TI - [Serological survey of para-influenza 3 virus in cattle in the Province of Valdivia]. PMID- 6258359 TI - Immune responsiveness in cattle fatally affected by bovine virus diarrhea-mucosal disease. PMID- 6258360 TI - [Significance of avian adeno-associated virus (AAAV) in serological studies of adenovirus infections in chickens]. PMID- 6258361 TI - Surveillance of influenza in pig herds in Czechoslovakia in 1974-1979. 2. Antibodies against influenza A (H3N2) and A (H1N1) viruses. PMID- 6258362 TI - [Demonstration of enteropathogenic Escherichia coli strains and rotaviruses in fecal samples from calves with diarrhea]. PMID- 6258363 TI - [Results of clinical application of methods of individual selection of chemotherapeutic preparations in the treatment of gliomas]. AB - The method of autoradiography for testing the efficacy of cytostatics with subsequent individually chosen chemotherapy is one of the components of rational therapy for neuro-oncological patients. Purposeful chemotherapy was applied in 17 cases with gliomas. Favourable results were recorded in 70.6% of them. Twelve patients received regular courses of treatment with one agent which inhibited DNA synthesis in vitro most potently (in 7 the therapeutic result was favourable), 5 patients were given course of polychemotherapy (favourable effect in 100%). Prolonged survival and a good remission allow autoradiography to be recommended as a method for the individual choice of antiblastic agents. PMID- 6258365 TI - Simultaneous bilateral cancer of the brease--evaluation of the use of a contralateral biopsy. AB - During a five-year period 299 female patients with breast cancer were treated by mastectomy. In 170 of the patients a biopsy of the contralateral upper lateral quadrant was performed during the operation. In 164 of the patients with primary carcinoma of ductal origin only 7 cases of malignancy in the contralateral biopsy were observed. In six females (3.5%) the primary cancer was of lobular origin and in three of these patients (50%) the contralateral biopsies showed lobular carcinoma in situ (LCIS). It is concluded that random contralateral biopsies of the breast should be restricted to patients with a primary cancer of lobular origin. PMID- 6258364 TI - Energy metabolism of the peritoneal membrane in silica-induced peritonitis. A biochemical and enzyme histochemical study. AB - Oxygen and glucose consumption and lactate production of the peritoneal membrane and intra-abdominal adhesions were measured in rats after a single intra peritoneal colloidal silica injection. Enzyme histochemical studies were made of lactate dehydrogenase, succinate dehydrogenase, NADH2-diaphorase, NADPH2 diaphorase, glucose-6-phosphate dehydrogenase, glutamate dehydrogenase, acid phosphatase, leucylaminopeptidase and alkaline phosphatase in the peritoneal membrane. Anaerobic glycolysis comprises 47% of the total glucose consumption in the the normal peritoneum. Glucose consumption and lactate production of the peritoneal membrane increased sharply in the early phase of silica-induced peritonitis and stayed at a high level for a week indicating an enhanced anerobic metabolism. Oxygen and aerobic glucose consumption increased more slowly than anaerobic glucose consumption and reached their maxima 1 week after silica injection, indicating that the rate of aerobic metabolism is also higher in chemical peritonitis than in the controls. On the other hand, glucose consumption and lactate production increased in a parallel fashion in adhesions and in the peritoneum in the early phase of peritonitis. However, the maximum and later levels were less in adhesions than in the peritoneum. In the enzyme histochemical study high activities of enzymes indicating anaerobic energy metabolism and metabolism via the pentose phosphate shunt were seen in cells of the peritoneal membrane during the early phase of peritonitis. No activity was identified in enzymes indicating aerobic energy metabolism and increased catabolism before the end of the first week. PMID- 6258366 TI - Longitudinal study on rotaviruses in stool samples during the first year of life. PMID- 6258367 TI - Human papillomavirus infection of the cervix: the atypical condyloma. AB - We report on 162 cases of human papillomavirus (HPV) infection of the cervix seen in a two-year period in which the cell sample showed such marked atypia that errors of interpretation could easily have been made. These atypical condylomata are difficult to diagnose cytologically as well as histologically because they mimic dysplasia or carcinoma in situ and, on smears, even invasive squamous carcinoma. HPV particles associated with fibrillar material were found within nuclei of these lesions; their nature was further proved by the immunoperoxidase test. This new form of HPV infection of the cervix showed a 9.1% rate of progression to more advanced cervical lesions. The cytologic finding of atypical condylomata is an indication for colposcopy, confirmative biopsy and appropriate treatment. PMID- 6258369 TI - Syndrome of inappropriate ADH secretion concealed by hypokalaemia due to ectopic ACTH production. AB - A case is described of a patient with an oat cell carcinoma of the bronchus with moderately elevated levels of plasma corticotrophin (ACTH) and antidiuretic hormone (ADH). Ectopic secretion of ACTH induced severe hypokalaemia and concealed the effects of concomitant ADH secretion on renal function. Normal renal responsiveness was restored following correction of hypokalaemia. The hypokalaemia was associated with evidence of a marked increase in corticosteroid secretion but plasma ACTH concentrations did not show a proportionate elevation. Chromatographic studies on tumour extracts suggest that the presence of a large fraction of high molecular weight ACTH in plasma could explain this discrepancy. PMID- 6258368 TI - The influence of sex hormones on acne. AB - The sebaceous glands are stimulated by androgens produced in the skin itself. This explains why elevated androgen levels are seldom found in blood and urine from patients with acne. The most potent androgen is dihydrotestosterone (DHT), which is formed in the target cells, i.e. in the sebaceous glands, by a 5 alpha reduction of testosterone. DHT is then bound to a specific receptor protein and translocated into the cell nucleus. In young persons genetically predisposed to acne a temporarily increased local DHT-formation has been postulated. In women androstenedione appears to be the major pre-hormone for DHT-formation. Adrenal androgens may account for prepubertal acne. Estrogens and progesterone influence acne only in high, unphysiological doses. Therapeutically we are waiting for a safe effective anti-androgen for topical use. PMID- 6258370 TI - Role of the adenylate cyclase system in altered insulin release from islets of Langerhans of aging rats. AB - In attempting to understand the causes of the hyperglycaemia observed in aging populations and to determine the mechanism(s) for the diminished in vitro insulin release from islets of Langerhans of older rats, the adenylate cyclase-cyclic AMP system was studied in isolated islets from 12 month old and 2 1/2 month old (control) male rats to determine its role in this altered insulin secretion. Islets of Langerhans were isolated by collagenase digestion and then either incubated in the presence of low or high concentrations of glucose for studies of insulin release or were sonicated and assayed for determinations of activities of adenylate cyclase and phosphodiesterase. Insulin release was identical from islets of 12 month old and 2 1/2 month old rats to 2.8 mM D-glucose, while in the presence of 16.7 mM D-glucose, insulin release was decreased by 33% (P less than 0.02) from islets of the older animals. Adenylate cyclase activity was diminished by 60% (P less than 0.005) from the 12 month old rats as compared with islets from the 2 1/2 month old controls, while low Km phosphodiesterase activity was similar in islets from both groups of animals. From these studies it appears that the adenylate cyclase-cyclic AMP system may play a role in the altered insulin release from islets of aging rats. PMID- 6258371 TI - A change in the adrenocortical response in perinatal rat offspring given betamethasone 17,21-dipropionate. AB - The potent synthetic glucocorticoid betamethasone 17,21-dipropionate (BMDP) produces adrenal hypertrophy in the rat foetus at late pregnancy by mediation of the hypothalamo-pituitary system, but causes adrenal atrophy, and acts as a normal glucocorticoid, in the adult rat. The change of the adrenal cortical response to the BMDP treatment was investigated in perinatal rat offspring. The pituitary ACTH potency was also determined in rat foetus treated with BMDP. The time course of the adrenal corticosterone level after the BMDP treatment was similar to that of the plasma level on day 19 to 21 in the rat foetus from the adrenalectomized mother, both decreased at 2 h, but rose gradually at 4 h to 6 h, exceeding the control level at 24 h and 48 h after the BMDP treatment. The pituitary ACTH potency in the foetus decreased at 24 h and 48 h after the BMDP treatment, suggesting that ACTH released from the foetal pituitary stimulated adrenal corticoidogenesis. Maternal adrenalectomy did not essentially alter this stimulating activity of BMDP, which appeared in the perinatal rat offspring, only when BMDP was administered during the foetal period. These findings suggest that the hypothalamo-pituitary adrenocortical response to the treatment with BMDP drastically changes at the early neonatal age. PMID- 6258372 TI - Modification of pituitary-adrenal feedback sensitivity in young rats by neonatal treatment with cortisol. AB - Neonatal exposure of rats to cortisol acetate was found to alter pituitary adrenal feedback regulation at 20-25 days of age. Plasma levels of adrenocorticotrophin (ACTH) after ether stress were reduced in cortisol-treated rats pre-treated with 100 microgram corticosterone/100 g body weight, while rats given vehicle neonatally did not show suppression of the ACTH response below levels in animals given saline only or not injected as pre-treatments. Neonatal cortisol increased sensitivity to dexamethasone in inhibition of the stress response; cortisol-treated animals had a reduced plasma corticosterone response to stress 3 h after pre-treatment with 1.25, 2.5, 25, or 250 microgram dexamethasone/100 g body weight, while the stress response in animals given vehicle neonatally was not inhibited by the lowest dosage of dexamethasone. Neonatal cortisol treatment did not affect corticosteroid-binding globulin (CBG) binding capacity in plasma of 25-day-old animals. Thus, neonatal treatment with cortisol appears to increase feedback sensitivity to circulating corticosteroids at 20-25 days of age. PMID- 6258373 TI - Effects of oestradiol benzoate (OeB) and human chorionic gonadotrophin (hCG) on the testes and accessory sex glands of the rat. AB - It has been suggested that treatment of intact male rats with oestradiol benzoate (OeB) causes an interference with testosterone (T) production by the testes by a direct inhibitory effect on steroidogenesis. To test this hypothesis, different doses (5, 10 or 25 IU) of hCG were administered concomitantly with 50 microgram of OeB to adult intact or hypophysectomized male rats. The testicular and plasma testosterone, and serum hCG levels were determined. The sex accessory weights were recorded. In the intact OeB-treated group of animals, hCG stimulated both the secondary sex organs and plasma testosterone levels above the intact control group. However, in hypophysectomized animals, although plasma testosterone levels increased above that of intact controls, their secondary sex organ weights did not. Moreover, inspite of high circulating hCG levels, the testicular testosterone content and concentration remained suppressed in OeB-treated animals. The reason for such dichotomy of hCG action on OeB-treated animals is not clear at present. PMID- 6258374 TI - Cannabis and its effect on anesthesia. PMID- 6258375 TI - Pretreatment with non-depolarizing muscle relaxants: the influence on neuromuscular transmission and pulmonary function. AB - The influence of pretreatment with non-depolarizing muscle relaxants on the neuromuscular transmission was evaluated in 40 healthy, awake, non-premedicated volunteers using train-of-four (TOF) nerve stimulation and measurement of vital capacity (VC), inspiratory force (IF), peak expiratory flow (PEF), and forced expiratory volume in the first second (FEV1). The subjects were randomly allocated to one of four groups: group I received pancuronium 0.01 mg/kg; group II pancuronium 0.015 mg/kg; group III gallamine 0.3 mg/kg, and group IV gallamine 0.4 mg/kg intravenously. TOF ratio decreased significantly in groups II, III and IV but not in group I following precurarization. Median (25 and 75 percentiles) TOF ratios after pretreatment wer 94(92-96), 89 (86-93), 92 (89-93), and 93 (87 96), respectively. Overall there were decreases in VC, IF, and PEF, but only the decrease in PEF was statistically significant in all four groups. FEV1 was unchanged. The most pronounced decrease in VC, IF, and PEF (11, 29, and 29%, respectively) was seen one subject in group II with a TOF-ratio of 63 following precurarization. Four subjects (20%) in groups II and IV experienced difficulty in breathing. All subjects were, however, able to maintain head lift for more than 10 s, and none needed respiratory support. Seventy percent of all subjects had various minor complaints as, for instance, blurred vision and difficulty in swallowing. It is concluded that the higher doses of pancuronium 90.015 mg/kg) and gallamine (0.4 mg/kg) cannot be recommended for routine precurarization. PMID- 6258376 TI - Cerebrospinal fluid markers of disturbed brain cell metabolism in patients with stroke and global cerebral ischemia. AB - Adenylate kinase activity was found in 32 of 34 samples of cerebrospinal fluid (CSF) from 21 patients with stroke and seven patients with global cerebral ischaemia (GCI). The light absorbance values of the spectrum 400-650 nm revealed the scanty occurrence of haemoglobin products in the CSF in some patients. No correlation was found between the absorbance values at 415 nm, reflecting oxyhaemoglobin, and the adenylate kinase activities. Thus, a main contribution to the adenylate kinase activity in CSF by leakage of this enzyme from erythrocytes could be ruled out. Instead increased leakiness of the brain cells, having an impaired metabolism due to insufficient supply of oxygen and glucose, was the most plausible cause of the findings. The quotient between the adenylate kinase activity and the light absorbance at 415 nm seemed to reflect the extent of ischaemically deranged brain tissue in the GCI patients, while the CSF-lactate values were not correlated to the clinical outcome. Glutathione, an intracellular tripeptide, was more often found in the CSF from GCI patients than from stroke patients. PMID- 6258377 TI - Chromatin-negative Klinefelter's syndrome with focal megalencephaly. AB - At autopsy, 72-year-old white male with chromatin-negative Klinefelter's syndrome, mental retardation, psychotic behavior, and carcinoma of the lung was noted to have right unilateral focal cerebral and cerebellar megalencephaly with broad gyri, a cytoarchitectually abnormal cortex, and thickened cerebral vessels. Literature about the neuropathology of Klinefelter's syndrome and several cases of other chromosome aberrations (XYY and XO syndromes) are reviewed. These neuropathological changes are thought to be related to clinical manifestation. PMID- 6258378 TI - Cerebrospinal fluid enzymes in neurological diseases. AB - The activities of adenylate kinase, creatine kinase and lactate dehydrogenase were measured in cerebrospinal fluid and serum from 127 patients admitted to the Department of Neurology. All cerebrospinal fluid samples with hemoglobin greater than 1 mg/l were excluded. Upper reference limits for the enzyme determinations were established, using samples from patients without objective criteria of organic involvement of the nervous system. High enzyme activities did not correlate to any particular group of diseases and were also found in patients without organic brain diseases. We conclude that determination of the three enzymes in cerebrospinal fluid is of limited value in the diagnosis of neurological diseases. PMID- 6258379 TI - Effect of ACTH treatment on CSF and blood lymphocyte subpopulations in patients with multiple sclerosis. AB - Patients with active multiple sclerosis (MS) were examined for T lymphocytes (E rosette-forming cells, E-RFC) and IgG concentrations in cerebrospinal fluid (CSF) and in blood, and for other lymphocyte subpopulations in blood, before and after treatment with adrenocorticotropical hormone (ACTH). Patients who responded to treatment had higher initial percentages of CSF T lymphocytes (93.1 +/- 3.0%) compared to patients who showed no clinical improvement (88.2 +/- 3.2%). After treatment, the responders had decreased CSF T lymphocyte levels (83.1 +/- 6.6%) while those of the nonresponders were unchanged (90.2 +/- 2.2%). In blood, T cell counts were unchanged, but "active" T cell levels showed a tendency to increase in responders and decreased significantly in non-responders. The percentage of Fc receptor-positive cells increased after treatment in both responders and nonresponders, and that of complement receptor-positive cells increased slightly in responders, but these changes were not statistically significant. Serum IgG concentrations decreased in eight of nine patients after treatment. CSF IgG concentrations were found to be increased, unchanged or decreased, after treatment with no significant differences between responders and nonresponders. The results suggests an involvement of the T lymphocyte in active MS. PMID- 6258380 TI - Fluoride uptake in enamel and dentin surfaces exposed to a fluoride-containing amalgam in vitro. a proton microprobe analysis. AB - Proton microprobe analysis was used to determine the fluoride concentrations in enamel and dentin surfaces exposed to a fluoride-containing and a conventional amalgam in vitro. After seven weeks of exposure, a considerable fluoride uptake was demonstrated from the fluoride-containing amalgam. The fluoride deposition was greater in the dentin than in the enamel. The greatest fluoride concentrations in enamel surfaces, about 4000 ppm, were found in the outer 0.05 micrometers of the tissue. In the dentin the greatest concentrations, about 9000 ppm, were found at a depth of 11.5 micrometers. This study demonstrates the ability of the fluoride-containing amalgam to deposit fluoride into dental hard tissues. PMID- 6258381 TI - Quantitative study of human Scarpa's ganglion and vestibular sensory epithelia. AB - Methods for counting vestibular ganglion cells and determining the densities of hair cells and intraepithelial basophilic inclusions (IBI) in samples of cross sectioned vestibular sensory epithelia are described. Data obtained by means of these methods in vestibular sensory epithelia and Scarpa's ganglia in individual temporal bones from subjects at different ages are presented. Both vestibular hair cells and nerve cells in Scarpa's ganglia are found numerically reduced in ears of aged individuals. Changes in the vestibular sensory epithelia appear to precede those seen in Scarpa's ganglion. The incidence of intraepithelial basophilic inclusions correlates with degeneration in the respective vestibular sensory epithelia. There are no striking differences in hair cells densities of the different vestibular sense organs of the same ear and from subjects at about the same age. PMID- 6258382 TI - The effects of inhibition of the strial Na+-K+-activated ATPase by perilymphatic ouabain in the guinea pig. AB - The endolymphatic effects of perilymphatic ouabain (2 X 10(-3) M) were followed in 3 guinea pigs using ion-sensitive micro-electrodes, enabling a Na+-related permeability increase to be identified. Investigation of the strial ultrastructural changes in 11 more animals revealed early swelling of the marginal cells, while the intermediate and basal cells became shrunken with characteristically dark-staining cytoplasm. The subsequent cellular alterations were complex. The findings suggest that a major function of the Na+-K+-activated ATPase is preservation of the normal intracellular environment, inhibition resulting in widespread indirect effects. General measures of strial function, consequently, do not document just ATPase inhibition. PMID- 6258383 TI - Antibiotic sensitivity of enteropathogenic Escherichia coli to mecillinam, trimethoprim-sulfamethoxazole and other antibiotics. AB - Forty-six clinical isolates of enteropathogenic Escherichia coli (EPEC) collected in Addis Ababa, Ethiopia, 1977--1978, were tested for susceptibility to 12 different antibiotics and beta-lactamase-production. Special reference was made to mecillinam and trimethoprim-sulfamethoxazole (TMP-SMZ) that were recently shown to be effective in the treatment of severe gastroenteritis caused by EPEC. Twenty-nine of the strains were of serotype 0111:B4. Thirty of the strains were resistant to 4 antibiotics or more, most of these strains belonging to serotype 0111:B4. For mecillinam, 19 strains had minimal inhibitory concentration (MIC) less than or equal to 0.2 microgram/ml, 27 strains had MIC 0.8--3.2 microgram/ml. Regarding TMP-SMZ, 41 strains had MIC less than or equal to 1 microgram/ml, 5 strains had 2--4 microgram/ml. No strain was resistant to gentamicin or nalidixic acid. Increased production of beta-lactamase was correlated to ampicillin resistance. PMID- 6258384 TI - Comparison of beta 1- and beta 2-receptor stimulation in oestrogen or progesterone dominated rat uterus. AB - Electrical stimulation of rat uterine preparations induced constant and reproducible contractions. The inhibitory effect of some adrenergic substances was tested on oestrogen- or progesterone-primed electrically stimulated rat uteri. The rank order of the relative potencies of some adrenergic agonists was shifted from Iso greater than E greater than Salb greater than Ne greater than H 133/22 greater than Phe greater than Clo in the oestrogen primed uterus to Iso greater than Salb greater than E greater than Ne greater than Phe greater than Clo greater than H 133/22 in progesterone primed uterus. The selective beta 2- agonist salbutamol was relatively more potent in progesterone treated rats than in oestrogen treated, while the beta 1-agonist H 133/22 was more potent in oestrogen dominated uterus. We therefore suggested that beta 2-receptors is dominating in the progesterone primed uterus, while both beta 1 and beta 2 receptors could be found in oestrogen primed uterus. No dissociation between the inhibitory effect on contractility and the cAMP increasing effect of isoprenaline could be demonstrated in rat uteri. PMID- 6258385 TI - Plasma and brain levels of delta 6-THC and seven monooxygenated metabolites correlated to the cataleptic effect in the mouse. AB - The brain and plasma levels of unchanged delta 6-tetrahydrocannabinol (delta 6 THC), 7-hydroxy-delta 6-THC, the five side-chain hydroxylated delta 6-THC derivatives and 1 alpha, 2 alpha-epoxyhexahydrocannabinol (EHHC) were correlated to the cataleptic effect in the mouse up to 60 min. after intravenous administration of radiolabelled compounds in the range 1.3 to 12.4 mg/kg. All cannabinoids except delta 6-THC and 1"-hydroxy-delta 6-THC showed a very good correlation between brain/plasma concentrations and cataleptic effect. 4"-Hydroxy and "1-hydroxy-delta 6-THC reached the highest concentration in the brain but the most potent cannabinoids were delta 6-THC, 7-hydroxy-, 3"-hydroxy-delta 6-THC, and EHHC followed by 5"-hydroxy-, 4"-hydroxy-, 2"-hydroxy-, and 1"-hydroxy-delta 6-THC in decreasing order. It was concluded that structural rather than pharmacokinetic features are most important in determining the psychoactivity of the various cannabinoid metabolites of THC. PMID- 6258386 TI - Investigation on the mutagenicity in the Ames test of 1 alpha,2 alpha epoxyhexahydrocannabinol and its conversion by deactivating enzymes. PMID- 6258387 TI - The role of sodium pump activity in the hyperpolarization and in subsequent depolarization of smooth muscle in response to stimulation of post-synaptic alpha 1-adrenoceptors. AB - The electrical and mechanical activities of guinea pig taenia coli smooth muscle were measured by a "sucrose gap" technique. Under the same experimental conditions the ionic content of smooth muscle was also measured. The mean value of the resting potential was 56.9 +/- 1.1 mV (S.E.M.; n = 46). In normal Krebs solution immediately after dissection intracellular sodium amounted to 30.1, and intracellular calcium to 1.5 mmole x kg-1 wet weight. In response to adrenaline administration there was a Ca-dependent hyperpolarization (peak, 6.8 +/- 0.3 mV S.E.M.; n = 5) and an increased Na efflux with a rate constant (k) of 0.16 min-1 (60'). Removal of adrenaline was followed by so-called "postadrenaline depolarization" i.e. the decrease of the membrane potential was greater than the initial rise, an effect enhanced by ouabain (2 X 10(-5) M). Clonidine (5.3 X 10( 6) M), a selective presynaptic-adrenoceptor (alpha 2-receptor) stimulant failed to produce hyperpolarization, however, phenylephrine (5 X 10(-5) M) a pure postsynaptic alpha-adrenoceptor (alpha 1-receptor) stimulant produced a similar effect as adrenaline. In addition, yohimbine (1.4 X 10(-6) M), a typical presynaptic alpha-adrenoceptor inhibitor failed to affect the action of adrenaline or phenylephrine. These facts indicate that the alpha 1-adrenoceptors present on the smooth muscle are different from those situated presynaptically on the cholinergic nerve terminals modulating the release of acetylcholine. The effect of ouabain to lower membrane potential proved to be Ca2+-dependent. The intracellular sodium content was enhanced by ouabain from 30.1 to 90.9 +/- 4.7 mmole x kg-1 wet weight (60'). On washing out ouabain, hyperpolarization "post ouabain hyperpolarization" was detected, i.e. the rise of membrane potential was greater than the initial fall. It is suggested that the sodium pump plays a significant role in the post-ouabain hyperpolarization. Direct calculation of sodium movements suggests that the sodium permeability is about 3.7 p-mole x cm-2 x sec-1 and the pump generates a current of 1.06 X 10(-7) A x cm-2 which, in fact, while crossing the smooth muscle membrane with a resistance of 30-60 k omega cm2 would produce a potential difference of 3.2-6.4 mV. It is suggested that the electrogenic sodium pump may contribute to the resting membrane potential about 15 mV, a value obtained from the summation of depolarization induced by ouabain and hyperpolarization produced by adrenaline. PMID- 6258388 TI - Ganglionic blocking effect of indomethacin and other prostaglandin synthetase inhibitors. AB - The effect of various prostaglandin (PG) synthetase inhibitors such as indomethacin, diclofenac, fenoprofen, niflumic acid and sulindac was studied on the isolated sympathetic ganglion of Rana esculenta. It was found that all the tested drugs inhibited synaptic transmission, an effect related to the inhibition of PG synthetase. It has been suggested that PGF2a might be involved in the modulation of synaptic function in the frog sympathetic ganglion. PMID- 6258389 TI - The septo-hippocampal pathway: electrophysiological observations. AB - In 40 rats immobilized with gallamine evoked field potentials were elicited in the dorsal hippocampus by stimulation of the septal nuclei. Latency of the septohippocampal evoked potential (SHEP) elicited by stimulation of the medial septal nuclei, the variations of latencies and amplitudes with increasing stimulus intensities as well as the occurrence of frequency potentiation and post tetanic potentiation allow the conclusion that the SHEP registered in the stratum granulare of dentate gyrus is mainly monosynaptically elicited. Nevertheless some data discussed in the paper point to the existence of a more complicated and not exclusively monosynaptic activation of granular cells caused by septal stimulation. PMID- 6258390 TI - Receptors acting through adenylate cyclase in the CNS. AB - The author summarizes the current literature on neurotransmitters (dopamine, noradrenaline, serotonin and histamine) acting through adenlyate cyclase and also those ating direcctly without the intermission of c-AMP. The criteria of receptor binding are also stressed. The characteristics of D1 and D2 dopaminergic, beta1 adrenergic, H1 and H2 histaminergic receptors, their localisation and specific antagonists resp. agonists are emphasized too. Finally a new model is presented where adenylate cyclase and ionophore share a common receptor. PMID- 6258392 TI - Inhibition of synaptic transmission by morphine and its antagonism by Ca++ in the isolated sympathetic ganglion of frog and rat. AB - Synaptic transmission is inhibited by morphine in isolated sympathetic ganglia of frog and rat. This action of morphine can competitively be antagonized by naloxone, nalorphine as well as by increasing the Ca++ concentration of the medium. The morphine antagonistic action of Ca++ can be suspended by Mg++ applied in an equimolar concentration. These results show that morphine inhibits synaptic transmission by shifting the ionic balance necessary for transmitter release. PMID- 6258391 TI - Effect of ACTH on prostaglandin induced vascular permeability. AB - Increased vascular permeability was induced by prostaglandin E2 (PGE1), arachidonic acid and compound 48/80 in male rats. Natural ACTH in a dose dependent manner inhibited Evans blue exudation elicited by arachidonic acid or compound 48/80, however, it was ineffective against PGE1. ACTH4--10 (d-Phe7 and 1 Phe7) injected together with the prophlogistic agents depressed the arachidonic acid and compound 48/80 induced vascular reaction. Indomethacin pretreatment inhibited the effect of arachidonic acid on vascular permeability suggesting that arachidonic acid evoked its vascular activity by means of affecting the endogenous synthesis of prostaglandins and, on the other hand, the prostaglandin system played a role in the vascular permeability inducing effect of compound 48/80. ACTH4--10 peptide fragments free of steroidogenic action and natural ACTH inhibited locally the in vivo formation of PGS from arachidonic acid in the rat skin, resulting in a nonspecific decrease of local inflammation. PMID- 6258393 TI - A simulation study of a neuron in a simple muscle control system. AB - The mechanism underlying signal transmission through the accessory neuron of the muscle receptor organ in the crayfish abdomen was examined experimentally and by computer simulation. The mathematical model of the accessory neuron and its synaptic inputs was based, in part, on previous neuronal models studied by Stein (1965) and Rall (1964). The model predicted with considerable accuracy the behaviour of the experimental system in a number of situations. It was possible to determine in some detail the mechanisms underlying the frequency response characterized by a threshold and an approximately linearly increasing response for stimulus intensities above threshold. Furthermore, we were able to explain the observation that the accessory cell transforms a regular input train from a stretch receptor into an irregular output train. The highly branched structure of the dendritic tree, combined with a firing threshold in the dendrites which prevents action potentials from invading large parts of the dendritic tree, seems essential in determining these properties. PMID- 6258394 TI - Neuronal VIP in salivary glands: distribution and release. AB - Nerves containing vasoactive intestinal peptide (VIP) were observed in salivary glands of rat, cat and man. VIP nerves were numerous in the cat while they were moderate in number in rat and man. The measured concentrations of immunoassayable VIP were in agreement with the immunohistochemical findings. Electrical stimulation of the feline chorda lingual nerve, which stimulates salivary secretion and local blood flow, resulted in a marked elevation of VIP in the venous effluent from the submandibular gland. VIP was not measurable in saliva. Gel permeation chromatography of extracts from cat submandibular gland and from venous plasma collected before and during nervous stimulation revealed one immunoreactive peak with an elution position identical to that of highly purified porcine VIP. The finding of neuronal VIP in salivary glands, its release upon nerve stimulation and its known effect on local blood flow support the view that VIP is a neurotransmitter in the salivary glands. PMID- 6258395 TI - Temporal dissociation between the negative inotropism and the increase in cyclic GMP level induced by choline esters in spontaneously beating rat atria preparations. AB - The effects of acetylcholine and carbacholine on cyclic GMP levels and contraction amplitude were investigated simultaneously in spontaneously beating rat atria preparations. Both drugs at the concentrations of 5 x 10(-7) M or higher produced a very rapid decline of amplitude. However, the cyclic GMP levels was not elevated earlier than 5 s later, when the amplitude was already reduced to 50% of the initial value. Concentrations of acetylcholine below 5 x 10(-7) M were not able to affect the cyclic GMP level, although they reduced the contractility significantly. Acetylcholine had no effect on the cyclic AMP level. The data demonstrate that cyclic GMP does not mediate the negative inotropic effect of choline esters in rat atria preparations. PMID- 6258396 TI - [Antibody detection in hepatitis A outbreaks]. PMID- 6258397 TI - Effect of glucosamine on phenotype mixing of vesicular stomatitis virus with avian sarcoma virus. AB - The effect of glucosamine on phenotypic mixing between vesicular stomatitis virus (VSV) and avian sarcoma virus (ASV) was studied. Phenotypic mixing decreased with increase in glucosamine concentration, and, in the presence of 20 mM glucosamine, was no longer detectable. In the presence of 20 mM glucosamine, cells still produced 10(2)--10(3) focus forming units (FFU) of ASV and 10(6) plaque forming units (PFU) of VSV per milliliter. These results suggest that cells producing a relatively large amount of ASV (more than 10(3) FFU/ml) are essential for phenotypic mixing of VSV with ASV. PMID- 6258398 TI - Complete in vitro DNA replication of SV40 chromatin in digitonin-treated permeable cells. AB - A permeable cell system has been developed by treatment with digitonin for studying in vitro DNA replication of chromatin. DNA replication of simian virus 40 nucleoprotein complexes (SV40 chromatin) in digitonin-treated permeable cells was analyzed by electrophoresis in agarose-gel. Autoradiography of the agarose gel revealed that [32P]dCTP was incorporated in SV40 DNA I, II and replicating intermediates. The time course of the incorporation indicated the complete replication of SV40 DNA and chromatin with a full number of nucleosomes. The digitonin-treated permeable cell system will serve as a useful system for studying in vitro DNA replication of chromatin. PMID- 6258399 TI - Angiotensin-converting enzyme in newly detected sarcoidosis. With special reference to enzyme levels in patients with erythema nodosum. AB - Serum angiotensin-converting enzyme (SACE) was measured in 56 patients with sarcoidosis within three months after diagnosis. Serial analyses were performed in 42 patients, who were followed for two months to one year. SACE was elevated in 49 (70%) of the patients at some time during the period of observation. Erythema nodosum (EN) was present in 14 patients. Only one out of seven had elevated SACE during EN, but four months later SACE was elevated in all 14. In this group there was a negative correlation between SACE and S-lysozyme. Among 42 patients without EN the frequency of SACE elevation was rather constant, about 60%. In half of the patients SACE was normal at first examination, and subsequent elevation was observed in 19%. SACE and S-lysozyme were positively correlated. Enzyme activity was independent of mode of presentation, but a non-significant trend toward higher SACE in patients with pulmonary involvement was observed, and changes in SACE were roughly correlated to roentgenological changes. Among healthy controls, significantly higher SACE levels were found in children up to 17 years of age (reference interval 21.2-42.2 U/ml) than in adults aged 18-65 years (12.0-36.8 U/ml). The observations on patients with sarcoidosis demonstrate that a unique pattern of SACE occurs in those with EN, different from that of patients without EN. The findings support the view that EN is a hallmark of acute onset sarcoidosis. The value of serial SACE analyses is emphasized. PMID- 6258400 TI - The role of wild birds in the spread of influenza viruses. AB - Eggs deposited by different migrating wild bird species in pond farm areas in Hungary were examined for yolk antibodies to different variants of human A/H3N2 influenza virus. Antibodies to Victoria/75 and Texas/77 occurred in 17.9 and 32.0% of gull eggs, and 5.6 and 16.4% of common tern eggs, respectively, while antibodies to A/H1N1/77 occurred in roughly similar proportions (10.2 and 13.4%) in the eggs of both species. Infection of the gull and tern populations of given areas by human and avian influenza A viruses differed greatly in two consecutive hatching periods. While in 1978 7.6 and 1.1% of the gull and tern eggs, respectively, contained antibodies to the avian subtype Havl, no such antibodies were found in 1977. Subtype A/H3N2/Texas/77 virus was isolated from adult gulls and 1-3 weeks old gull chicks, and subtype H1N1 virus from mallard ducks. Three months before the onset of the Texas/77 epidemic, 95% of SPF chickens, and 71-81% of chickens hatched 3 months after termination of the A/H1N1/77 epidemic, had had HI, VN and SRH antibodies to the Texas/77 strain and A/H1N1/77 strains, respectively. PMID- 6258401 TI - Susceptibility of birds to type-B influenza virus. AB - Among Zoo birds and migrating wild birds examined serologically during an outbreak due to influenza B virus, 4.1% were found to have serum antibodies to the agent. Evidence of avian susceptibility to the agent was emerging from reisolations of the virus and primary and secondary HI antibody response of the birds in subsequent infection experiments performed on adult pheasants and mallards, as well as one-day-old domestic ducklings and chicks. The virus persisted in the pheasants for at least three weeks, and adult pheasants, mallards and domestic ducklings were found to transmit it by contact to part of their susceptible mates. PMID- 6258402 TI - Promoting effect of feeder cells in maintenance of adult rat hepatocytes. AB - A procedure is described for maintaining primary cultures of adult rat hepatocytes for prolonged periods of time on layer of irradiated mouse fibroblast cell line (C3H/1OT1/2) and on a secondary lung fibroblasts obtained from Sprague Dawley rats. Morphologically and ultrastructurally the cocultivated hepatocytes retained many characteristics of hepatocytes in vivo. Within 24 hours after seeding, the individual cells were attached on the feeder cell layer and the in vivo polarity of the liver cells reappeared. Electron microscope studies demonstrated the appearance of newly developed bile ducts and junctions between hepatocytes as well as between hepatocytes and feeder cells. Histochemically, these cells were positive for glucose-6-phosphatase and for glycogen. After 14 days in culture the hepatocytes could be reseeded onto fresh C3H1OT1/2 cells. In contrast, hepatocytes maintained on plastic substrate lost their glycogen content and the epithelial character of the liver cells after 5 days in culture, and by day 10 this culture became predominantly fibroblastic. It is suggested that hepatocytes maintained on an irradiated fibroblast feeder layer provide a valuable approach for studying the morphogenesis, cytotoxicity, or the metabolism of different chemicals in vitro. PMID- 6258403 TI - Biochemistry of pain relief with intracerebral stimulation. Few facts and many hypotheses. AB - On the basis of data obtained from subprimates subjected to acute pain stimuli, it has been hypothesized that the suppression of chronic pain in man during stimulation in the periventricular region involves endogenous opioid mechanisms. However, there is at present no direct and unequivocal proof that the pain relief in man is necessarily and entirely dependent upon such mechanisms. There exist several putative substances with opiate-like properties but they are difficult to identify. The assay methods lack specificity and cross-reactions are common. There are only a few studies published on the influence of intracerebral stimulation in man on the CSF-content of opioid substances; the changes observed are inconsistent, and data are only given on patients having satisfactory pain relief. Furthermore, measurements have been made only during the course of a few hours and nothing is reported on the relationship between the changing concentrations of the substance and the level of pain. The observation that Naloxone may reverse the effect of intracerebral stimulation has become the keystone in postulating common mechanisms for stimulation-produced pain relief and morphine analgesia. The fact, that Naloxone is sometime ineffective or has to be used in huge, and unphysiological, doses is generally disregarded. There are a number of substances which may serve as neurotransmittors in pain transmission and pain inhibition but their mode of action in the generation and suppression of chronic pain is entirely unknown. Data collected from various European clinics covering more than 200 patients subjected to intracerebral stimulation show that the outcome of this treatment is highly unpredictable. Intracerebral stimulation as a clinically useful treatment of chronic pain can not be further developed unless hard data on its biochemical background in man are provided. PMID- 6258404 TI - Tumor antigens on neoplasms induced by chemical carcinogens and by DNA- and RNA containing viruses: properties of the solubilized antigens. PMID- 6258405 TI - Nutrition and its relationship to cancer. PMID- 6258406 TI - Catalytic reaction of copper complexes with superoxide. PMID- 6258407 TI - Superoxide anion and superoxide dismutase activity in arthritic conditions. PMID- 6258408 TI - Multilocular renal cysts: radiologic-pathologic correlation. AB - Multilocular renal cyst, a well-encapsulated benign lesion consisting of multiple noncommunicating cysts, is an uncommon entity of uncertain nature. A spectrum of histologic findings and multiple theories of pathogenesis have resulted in numerous names for the lesion, including multilocular cyst, benign cystic nephroma, cystic hamartoma, cystic lymphangioma, cystic Wilms tumor, and Perlmann tumor. We believe these names, and others, refer to the same entity, namely multilocular cyst. Radiographically a multicystic renal mass which is often calcified and which may partially protrude into the renal pelvis is seen. Although angiography cannot definitively exclude a malignant tumor, a distinctive sonographic appearance-multiple cystic masses separated by highly echogenic septa is highly suggestive of multilocular renal cyst. Inclusion of this lesion in the preoperative differential diagnosis of a solitary and presumed malignant renal mass may have significant therapeutic implications. PMID- 6258409 TI - Cystic hepatic neoplasms: complementary roles of CT and sonography. AB - Nine patients with cystic or necrotic hepatic neoplasms had findings on computed tomography (CT) that strongly suggested benign cystic disease of the liver. Sonography depicted the true morphology of these cystic lesions more clearly than CT, and the sonographic findings virtually excluded uncomplicated hepatic cyst as a diagnosis. Important observations were wall thickness, mural nodules, septations, and fluid-fluid levels. The potential danger in over reliance on CT attenuation values and the complementary role of sonography and CT in such cases are stressed. PMID- 6258410 TI - CT of hepatoma: effects of portal vein obstruction. AB - CT images were studied in five patients with hepatocellular carcinoma associated with obstruction of branches of the portal vein. Two were solitary tumors located near the porta hepatis and were seen as low density areas. In addition noncancerous areas with impaired portal drainage also had lower densities than normally perfused areas. In one instance, gross and histologic studies performed on the resected specimen showed atrophy of hepatic tissue. The other three patients had disseminated tumors with multiple low density areas on CT. Additional low density areas were seen in patients with concomitant obstruction of branches of the portal vein. A decrease in portal blood flow will change the appearance of hepatocellular carcinoma of CT. PMID- 6258411 TI - Multilocular renal cysts and cystic renal tumors. PMID- 6258412 TI - Quantitative scintigraphy of sacroiliac joints: effects of age, gender, and laterality. AB - The effects of age, gender, and laterality on sacroiliac/sacral ratios obtained during quantitative joint imaging were assessed in 97 nonarthritic control subjects. For the entire group, the right sacroiliac-to-sacral mean ratio of 1.27 in 54 males was significantly higher (p less than 0.02) than the right mean ratio of 1.18 in 53 females. In both genders the right joint ratio tended to be higher than the left in all age groups. The difference in mean ratio between the two joints was wider for males than for females. The age did not affect the joint ratio in either gender. It is concluded that the range of normal sacroiliac-to sacral ratios are different for males and females and should be taken into account during a quantitative sacroiliac joint imaging examination. PMID- 6258413 TI - Glomus laryngicum superior: a case studied arteriographically. PMID- 6258414 TI - Variations of the circadian rhythm of cAMP in bronchial asthma after administration of fenoterol. AB - In the study of the physiology and therapeutic response of bronchial asthma the evaluation of adrenergic activity is of fundamental importance. References in the literature indicate a reduction of the intracellular concentration of cyclic AMP in asthmatic patients, as well as a reduction in the response to beta-adrenergic stimulants. This work intends to expose the possible effects of the prolonged administration of beta-stimulants (as employed in bronchial asthma therapy) on the levels of circulating cyclic nucleotides. From another perspective, we wish to relate the clinical improvement after beta-adrenergic therapy and the levels of cyclic AMP. Ten patients suffering from bronchial asthma were selected for the study, and cyclic AMP levels were determined at different hours during the day (in order to evaluate its circadian rhythm), before and after treatment with 5 mg of Fenoterol (beta-stimulant), three times a day during 20 days. The results showed a statistically significant (p less than 0.002) reduction in the levels of cyclic AMP in the asthmatics. An increase in circulating cyclic AMP was observed after treatment, remaining high throughout the day, and differing from pre treatment levels by 4.9 p.Moles after 9 hours to 2 p.Moles 13 hours after initiation of treatment. Prolonged administration of Fenoterol modifies the circadian rhythm of cyclic AMP, causing an increase in its circulating levels. The magnitude of this increase is of less amplitude than the one observed after the administration of a single dose of Fenoterol and immediate determination. PMID- 6258415 TI - Pathogenesis of hypertrophic cardiomyopathy: hypotheses and speculations. PMID- 6258416 TI - Effects of angiotensin-converting enzyme inhibition on blood pressure and plasma renin activity in essential hypertension. AB - Oral converting enzyme inhibitor SQ14225 was administered in 11 patients with essential hypertension, in order to investigate the role of the renin-angiotensin system in the regulation of blood pressure in essential hypertension. In the sodium-repleted state (150 mEq sodium intake for 6 days) in 11 patients, converting enzyme inhibitor decreased the average mean blood pressure from 113 +/ 2 to 106 +/- 2 mm Hg (p less than 0.001). Plasma renin activity increased with sodium depletion (30 mEq sodium intake for 3 days after furosemide treatment) from 1.26 +/- 0.07 to 3.26 +/- 0.48 ng/ml/hr (p less than 0.001). In the sodium depleted state the hypotensive effect of SQ 14225 was more pronounced (mean blood pressure 108 +/- 2 to 93 +/- 3 mm Hg). The decrease in mean blood pressure caused by the inhibitor correlated to the basal plasma renin activity (r = -0.53, p less than 0.02, n = 22 measurements). The results indicate that the renin-angiotensin system participates in the regulation of blood pressure in essential hypertension, even in the sodium-repleted state. This role of the renin angiotensin system in blood pressure regulation becomes more crucial during sodium depletion. PMID- 6258417 TI - Right ventricular infarction: relationships between ST segment elevation in V4R and hemodynamic, scintigraphic, and echocardiographic findings in patients with acute inferior myocardial infarction. AB - The relationship between ST segment elevation on the right precordial lead V4R and the hemodynamic, echocardiographic, and myocardial scintigrapic signs suggestive of right ventricular (RV) infarction was studied in 42 patients with acute inferior myocardial infarction. Twenty-two patients had ST segment elevation in V4R. Among these patients, a significant correlation was demonstrated between V4R ST segment elevation and the hemodynamic (p less than 0.001), scintigraphic (p less than 0.001), and echographic (p less than 0.02) criteria for acute RV infarction. These results support the validity of this new electrocardiographic sign as a practical means in aiding the clinical detection of RV involvement with acute transmural inferior myocardial infarction. PMID- 6258418 TI - Critical evaluation of continuous monitors for toluene diisocyanate. AB - This paper describes the experiments and the results of an exhaustive and critical laboratory study which evaluated the performance of continuous area and personal monitors popularly used in measuring the concentrations of TDI in industrial environments. The studies consisted of dynamic calibrations, the effect of humidity and temperature on the measurements, and the interferences due to commonly encountered contaminants in a TDI manufacturing plant. The response and resolution of the personal monitor for short-term fluctuations of TDI concentration in time and space are also reported. PMID- 6258419 TI - Echocardiographic mimicry of pericardial effusion. AB - Echocardiography is a sensitive technique for the detection of pericardial effusion, but the abnormal echocardiographic patterns seen with effusions are not, however, entirely specific for that diagnosis. This study describes four patients in whom anatomic structures, a coronary artery to coronary sinus fistula (one case) and tumors metastatic to pericardium (three cases), produced posterior and, in two cases, anterior spaces compatible with pericardial fluid. Echocardiographic patterns mimicking pericardial effusion have previously been reported in patients with anatomic abnormalities such as mitral anular calcification, pleural effusions, left atrial enlargement, anterior mediastinal or pericardial tumors, foramen of Morgagni hernia and pseudoaneurysm of the left ventricle. It appears that structures of fluid or tissue density, interposed between the heart and the airfilled lung, can produce echocardiographic patterns simulating pericardial effusion. PMID- 6258420 TI - Immunohistochemical identification of lysozyme in cutaneous lesions of alleged histiocytic nature. AB - Histiocytosis X, multicentric reticulohistiocytosis, juvenile xanthogranuloma, the "fibrous" type of dermatofibroma, dermatofibrosarcoma protuberans, and malignant fibrous histiocytoma are all characterized by dermal and/or subcutaneous infiltrates composed at least partially of cells having morphologic features suggestive of histiocytes. Paraffin-embedded tissues representing these conditions were stained for lysozyme (muramidase) with a peroxidase antiperoxidase technic. The cells of juvenile xanthogranuloma were rich in lysozyme. Some of the cells of histiocytosis X showed a positive pattern, and the cells of the other three conditions were essentially negative. This study confirmed the histiocytic nature of juvenile xanthogranuloma and multicentric reticulohistiocytosis, supported the interpretation that there is a histiocytic component in the lesions of histiocytosis X, and cast some doubt on the alleged histiocytic nature of "fibrous" dermatofibroma, dermatofibrosarcoma protuberans, and malignant fibrous histiocytoma. PMID- 6258421 TI - Angiotensin-converting enzyme in Crohn's disease and ulcerative colitis. AB - The relationship between serum angiotensin-converting enzyme activity and inflammatory bowel disease was investigated in 37 patients who had Crohn's disease, 31 patients who had ulcerative colitis, and 104 control subjects. The enzyme activity tended to be depressed in Crohn's ileitis (P less than 0.05) and colitis, but not in Crohn's ileocolitis and ulcerative colitis. No increase in enzyme activity was observed in Crohn's disease ileum or colon or in ulcerative colitis colon. The granulomatous inflammation in Crohn's disease differs from that in sarcoidosis, in which striking elevation of angiotensin-converting enzyme is present in granulomatous tissue and frequently in serum. PMID- 6258423 TI - Opiates and the gastrointestinal tract. AB - Opiate peptides, encephalins and endorphins, originally isolated from the brain, have been detected by the immunocytochemistry and radioimmunoassay in the digestive system and localized in the distinctive endocrine-paracrine cells of APUD series of the gastrointestinal mucosa and the nerve fibers of the myenteric plexus. The physiological role of endogenous opiates is unknown but the spectrum of biological action on the digestive system resembles that of morphine and related drugs. They strongly affect gastrointestinal motility such as gastric and intestinal contractions, gastric emptying, intestinal transit, biliary pressure and defecation. They also increase gastric secretory activity and raise gastric mucosal microcirculation without affecting gastrin release. They inhibit pancreatic bicarbonate and enzyme secretion probably via suppressing the release of intestinal hormones, secretin and cholecystokinin. The actions of opiates on the motility and secretion can be reversed by specific opiate receptor antagonists, e.g. naloxone, indicating that opiate receptors may be involved in these actions. PMID- 6258422 TI - Presence of human papilloma viral antigens in juvenile multiple laryngeal papilloma. AB - Juvenile laryngeal papillomas, solitary laryngeal papillomas of the adult, and cylindric cell papillomas of the nose and sinuses were examined for the presence of papillomavirus antigens by means of immunocytochemistry. By using an antiserum capable of recognizing a common group antigen that reacts with papillomavirus antigens of different species, it was found that half of the juvenile laryngeal papillomas studied contained cells staining for papillomavirus antigens. No positive cells were found in adult solitary papillomas or cylindric cell papillomas. These results strongly implicate a human papillomavirus as the causative agent of juvenile multiple laryngeal papillomas. PMID- 6258424 TI - Research needs in the epidemiology of diabetes. Diabetes Epidemiology Workgroup, National Conference on Diabetes. PMID- 6258425 TI - Nosocomial herpetic infections in a pediatric intensive care unit. AB - A series of acute herpetic infections occurred among nurses and patients in a pediatric intensive care unit (PICU). Epidemiologic study revealed two separate time clusters of infections, one in early summer and another six weeks later. Restriction endonuclease analysis of DNA extracted from virus isolates showed that each time cluster was associated with a different genetic strain of herpes simplex virus (HSV) type 1 and provided evidence of cross infection between patients and nurses. Three nurses had herpetic whitlow; the husband of one had acute gingivostomatitis; a fourth nurse had acute pharyngitis. They had no previous history of HSV infection and sequential antibody testing of affected nurses showed 19S antibody in all initially positive serums, confirming primary infection. The data provide clear evidence that PICU personnel risk acquiring serious herpetic infections from patients and vice versa unless specific precautions are taken. Restriction endonuclease analysis of HSV DNA was useful in the epidemiologic study of the infections. PMID- 6258426 TI - An evaluation of influenza mortality surveillance, 1962-1979. I. Time series forecasts of expected pneumonia and influenza deaths. AB - Proposed in this paper is a new method of forecasting the expected number of pneumonia and influenza deaths based on a time series analysis of the historical mortality data. Currently, the method for forecasting the expected pneumonia and influenza deaths used by the Center for Disease Control is based on regression analysis. These forecasts are used to estimate the excess deaths attributable to pneumonia and influenza. Careful comparative analysis demonstrates that the proposed method provides a more accurate forecast of pneumonia and influenza mortality than the existing method. PMID- 6258427 TI - An evaluation of influenza mortality surveillance, 1962-1979. II. Percentage of pneumonia and influenza deaths as an indicator of influenza activity. AB - In this paper, the percentage of all deaths that are related to pneumonia and influenza (P & I ratio) is evaluated as an indicator of influenza activity and as a method to quantify the impact of influenza on mortality. Analysis of data from 1962-1979 indicates that the P & I ratio is an accurate indicator of influenza activity, as confirmed by independent systems of morbidity and laboratory surveillance. A rule using the P & I ratio for detecting an outbreak of an influenza epidemic was evaluated. It was found to be much more specific than a rule based on the regression model, but did not provide more timely detection of outbreaks of influenza during the past 17 years. The use of the P & I ratio in the autoregressive integrated moving average (ARIMA) model of forecasting provided the most accurate prediction of the expected pneumonia and influenza mortality. PMID- 6258428 TI - Age-specific prevalence of hepatitis A virus antibody in Thailand. AB - Serum specimens drawn at random from three geographically defined populations of healthy Thais were tested for antibody to the hepatitis A virus (anti-HAV) by radioimmunoassay. A total of 746 specimens were tested. The age by which 50 per cent were antibody positive was 4-5 years for residents of an urban Bangkok housing project, 8-9 years for rural villagers, and 10-11 years for urban Bangkok government school pupils. Overall, specimens from 97 per cent of Thai adults 16 years of age or older were anti-HAV positive. These data suggest widespread distribution of HAV in Thailand. PMID- 6258429 TI - The molecular basis of hemoglobin Grady. AB - DNA from individuals heterozygous for the extended alpha-chain variant Hb Grady were studied by gene counting and restriction enzyme analysis. Neither method indicated the presence of an extra (fifth) alpha gene, which argues that if this variant arose by unequal crossing over, the event most likely involved mispairing between alleles rather than between the separate alpha 1 and alpha 2 loci. PMID- 6258430 TI - Cytomegalovirus: subclinical infection or disease? PMID- 6258431 TI - Bleeding of the upper gastrointestinal tract and a hepatic mass. PMID- 6258432 TI - Infection in the renal transplant recipient. AB - The incidence of infection in the renal transplant patient is directly related to the net immunosuppressive effect achieved and the duration of time over which this therapy is administered. A second major factor in the causation of infections in this population is the nosocomial hazards to which these patients are exposed, ranging from invasive instrumentation to environmental contamination with Aspergillus species, Legionella pneumophila, Pseudomonas aeruginosa and other microbial pathogens. Careful surveillance is necessary to identify and eliminate such nosocomial sources of infection. The major types of infection observed can be categorized according to the time period post-transplant in which they occur: postsurgical bacterial infection in the first month after transplantation; opportunistic infection, with cytomegalovirus playing a major role, and transplant pyelonephritis in the period one to four months post transplant; and a mixture of conventional and opportunistic infections in the last post-transplant period. Conventional infection in this late period occurs primarily in patients with good renal function who are receiving minimal immunosuppressive therapy; opportunistic infection occurs primarily in patients with poor renal function who are receiving higher levels of immunosuppression. PMID- 6258434 TI - Croup and epiglottitis. PMID- 6258433 TI - The Dubowitz syndrome: further observations. AB - An autosomal recessive disorder characterized by intrauterine growth retardation, postnatal retardation, microcephaly, sparse hair, toe syndactyly, and characteristic facial appearance is now recognized as the Dubowitz syndrome. Five addition additional cases of the Dubowitz syndrome are reported, including 2 with documented vascular abnormalities. PMID- 6258435 TI - Adrenal responses to prostaglandin E2 in newborn lambs. AB - Prostaglandin E2 (PGE2) is present in fetal sheep and stimulates adrenal steroidogenesis in the fetal and newborn sheep. We have examined the site of this prostaglandin effect and the changes in adrenal responsiveness to exogenous PGE2 and adrenocorticotropic hormone (ACTH) in in vivo studies with newborn lambs. A bolus injection of PGE2 (50 micrograms) into the brachiocephalic trunk or descending aorta raised plasma cortisol (F) 25.3 +/- 4.5 (SE) ng/ml to 75.5 +/- 5.4 ng/ml at 15 to 30 minutes and 23.2 +/- 3.0 to 60.5 +/- 7.1 ng/ml at 15 to 30 minutes, respectively (both P less than 0.001). Intra-aortic infusion of PGE2 (1.25 micrograms/ml) produced a similar significant rise in F. Basal plasma F decreased from 34.3 +/- 7.4 ng/ml at 9 to 11 days to 14.1 +/- 4.0 ng/ml at 12 to 13 days and 18.2 +/- 5.7 ng/ml at 17 to 18 days. Peak F during a 60-minute PGE2 infusion was significantly greater at 9 to 11 days (127.3 +/- 14.6 ng/ml) than at the two later times (57.2 +/- 7.07 and 55.7 +/- 14.6 ng/ml, respectively, both P less than 0.01). The response to ACTH was greater 24 hours after birth than at 7 or 28 days of age. Injection of ACTH or alpha-melanocyte-stimulating hormone during an intra-aortic PGE2 infusion did not further elevate plasma F over the rise seen with PGE2 alone. The results suggest both direct and indirect stimulatory effects of PGE2 on adrenal function in newborn sheep, and are consistent with a role of endogenous PGE2 as an intermediate factor in ACTH action. PMID- 6258436 TI - Maternal plasma adrenocorticotropin and cortisol relationships throughout human pregnancy. AB - Adrenocorticotropin (ACTH) and cortisol in plasma were measured weekly from early in gestation through delivery in five women whose pregnancies were normal. During the twelfth week of pregnancy, the concentration of ACTH in plasma of blood samples obtained between 0800 and 0900 hours was 23 +/- 4.6 pg/ml (mean and SEM) and rose progressively to 59 +/- 16 pg/ml at 37 weeks. The levels of ACTH in plasma were significantly lower throughout pregnancy than those found in nonpregnant women. During labor and delivery, ACTH levels rose strikingly to values of 301 +/- 137 pg/ml. As pregnancy advanced, the concentration of cortisol in plasma increased progressively from 149 +/- 34 ng/ml (mean and SEM) at 12 weeks to 352 +/- 90 ng/ml at 26 weeks' gestation but changed minimally thereafter until labor commenced, during which values of 706 +/- 148 ng/ml were achieved. ACTH and cortisol secretory patterns over a 24-hour period were also investigated in one subject during each trimester of pregnancy. Diurnal variations were observed that were qualitatively similar to those seen in nonpregnant women. From the results of these studies, we conclude that ACTH levels are suppressed in plasma of normal pregnant women but are higher in late pregnancy than in early pregnancy. The rise in plasma ACTH concentrations, as pregnancy advances, in spite of increasing levels of plasma cortisol, estrogens, and progesterone, is suggestive of the possibility that a source of ACTH exists that is not subject to negative feedback control, that the clearance of free cortisol increases as pregnancy advances, or that there is an alteration in the metabolism of the ACTH precursor protein produced by the pituitary and/or placenta. PMID- 6258437 TI - Elevated free cortisol index in pregnancy: possible regulatory mechanisms. AB - Biologically active plasma free cortisol increases markedly in pregnancy. In this investigation the free cortisol index (FFI) in the plasma of pregnant and nonpregnant women was measured by a charcoal adsorption technique. The circadian FFI patterns were virtually identical in the two groups, but in gravid women there was a substantial and sustained elevation of the FFI. Sequential studies during gestation and post partum revealed increasing responsiveness of the maternal adrenal glands to adrenocorticotropic hormone (ACTH) and decreasing suppressibility of the FFI by dexamethasone as pregnancy advanced. Persistence of normal circadian rhythmicity in spite of a continuously elevated FFI and resistance to dexamethasone suppression suggest control of cortisol secretion by normal regulatory mechanisms in pregnancy with resetting of the maternal feedback mechanisms to higher levels. This resetting and the lack of manifestations of cortisol excess in pregnancy might result from tissue refractoriness to cortisol. Elevated free cortisol would be needed to maintain homeostasis. The necessary increase in the production of cortisol could be facilitated by an enhanced responsiveness of the maternal adrenal glands to ACTH. PMID- 6258438 TI - Granular cell tumor (myoblastoma) of the palpebral conjunctiva causing pseudoepitheliomatous hyperplasia of the conjunctival epithelium. AB - Granular cell tumors rarely occur in the ocular adnexal structures and only three cases have been described in which the eyelid alone was involved. I examined a patient who was, I believe, the first in whom a granular cell tumor appeared clinically as a conjunctival lesion. She was also the first patient with a granular cell tumor of the ocular adnexa to exhibit pseudoepitheliomatous hyperplasia of the overlaying epithelium, a pathologic feature associated with granular cell tumors originating elsewhere in the body. PMID- 6258439 TI - An ultrastructural study of alveolar permeability to cytochrome C in the rabbit lung: effect of exposure to 100% oxygen at one atmosphere. AB - Rabbits were exposed to 100% oxygen or to air at one atmosphere. No alterations were observed in the lung of rabbits breathing air for up to 66 hours or 100% oxygen for 24 hours; after 48 hours, inflammatory cells, chiefly neutrophils, were located in the interstitium of the lung. By 66 hours of oxygen, the number of inflammatory cells in the interstitial space was greater than at 48 hours. At 72 hours, alveolar space in focal areas of the lung was filled with edema fluid containing a lightly flocculent material, and more densely staining fibrin. In experiments for the study of alveolar permeability, cytochrome C was instilled through the tracheobronchial tree into alveoli and demonstrated ultracytochemically by its peroxidase activity. No electron-opaque reaction product was observed in control rabbits or in those breathing oxygen for 24 hours, indicating that the tracer did not leave the alveolar space. However, after 48 hours of the breathing of 100% oxygen, electron-opaque reaction product was localized to the basal lamina of alveolar capillaries in focal areas, whereas in other alveolar capillaries there was no reaction product in the basal lamina. Vesicles filled with reaction product were observed in Type 1 pneumocytes and in alveolar capillary endothelial cells within capillary loops having increased electron density in the basal lamina. After 66 hours of the breathing of 100% oxygen, virtually all alveolar capillaries showed electron-opaque reaction product in the basal lamina and in vesicles within Type 1 cells and capillary endothelial cells. Increased permeability of Type 1 pneumocytes appears as an early manifestation of oxygen-induced changes in the lung preceding pulmonary edema. The presence of numerous inflammatory cells in the interstitium and in alveolar capillaries may play some part in the pathogenesis of the oxygen-induced increase in alveolar permeability. PMID- 6258441 TI - Myocardial ischemia: ionic events in ischemia and anoxia. AB - The early stages of anoxemia and ischemia are associated with highly selective, reversible defects in sarcolemmal ionic exchange of potassium not necessarily the result of impaired sodium pump function. At a later stage structural defects in the membrane led to irreversible loss of intracellular potassium and creatine kinase. Similar stages can be demonstrated in the sarcolemmal selectivity for divalent cations. The degree of sarcolemmal injury from ischemia can be significantly influenced by the conditions of reperfusion. Reduced calcium content of blood reperfused for only 5 minutes can improve the mechanical recovery of ischemic rabbit ventricle. The influx of calcium during reperfusion impairs those processes required for restoration of sarcolemmal integrity. PMID- 6258442 TI - Corticosterone secretion after inhibition of prostaglandin synthesis by indomethacin. AB - Systemic indomethacin (Ind) administration decreased prostaglandin F (PGF) content of the rat adrenal to less than 1.4 pg/mg. This was less than 5% of the adrenal PGF content in the gelatin-treated (Gel) control group (34 pg/mg). Basal plasma corticosterone levels were increased by the Ind treatment. Since the calculated metabolic clearance rate for corticosterone was unchanged, this increase was attributed to an enhanced adrenal secretion rate that was secondary to elevated plasma ACTH concentration. Ether exposure in the presence of Ind did not stimulate a normal rise in plasma corticosterone or adrenal corticosteroidogenesis. Adrenal responsiveness to exogenous ACTH was reduced after Ind treatment. There was a normal rise in plasma ACTH levels following ether exposure confirming the adrenal as the site of inhibition. Systemic Ind treatment thus appears to have two sites of action in altering plasma corticosterone levels: 1) a direct effect on the adrenal, inhibiting normal secretion in response to acute elevations of plasma ACTH, and 2) an action at the pituitary or hypothalamic level, eliciting an increase in basal ACTH secretion. PMID- 6258440 TI - Carcinoma of type II pneumocytes: immunodiagnosis of a subtype of "bronchioloalveolar carcinomas". AB - Formalin-fixed paraffin-embedded tumor tissues from North American (N = 12) and Japanese (N = 11) patients with lung carcinomas were stained by the immunoperoxidase method for surfactant-specific apoprotein. Cytoplasmic and focal nuclear staining was seen in three "bronchioloalveolar carcinomas" occurring in Japanese patients. We refer to these three tumors as carcinomas of Type II pneumocytes. These neoplasms formed discrete masses with minimal growth along the alveolar septa at margins of the tumors. Papillary growth with lymphocytic infiltrates in the stalks of the papillary processes was the usual growth pattern. Focal noncaseating granulomas were seen in the stroma of 2 cases, and similar granulomas in the draining lymph nodes were noted in 1. The abundant cytoplasm was foamy, and the nuclei were generally vacuolated with frequent eosinophilic inclusions in the vacuoles. By electron microscopy, osmiophilic lamellar bodies or whorled lamellas were seen in the cytoplasm of the 3 tumors staining for surfactant apoprotein. The nuclei in 2 of the 3 cases contained tubular inclusions; the tubules had a diameter of 60 nm and a 20-nm core. PMID- 6258443 TI - Nonsteroidal adrenal feedback demarcates two types of pathways to CRF-ACTH release. AB - We have tested the relationship between corticosterone (B) and the number of adrenal glands on stimulated corticotropin (ACTH) levels in rats. Rats were supplied throughout the experiment with various doses of B in the drinking fluid beginning 15-20 h before adrenal surgery. Bilateral, unilateral, or sham adrenalectomy was followed on the 3rd day by the stimulus of ether vapor or ether and laparotomy with intestinal traction. Plasma ACTH levels 3 min after the stimuli were decreased by both the dose of B and adrenal number; the adrenal number of adrenals, although prestimulus ACTh and B levels were similar across groups. The decrease in ACTH after ether resulted from an interaction between the dose of B and the however there was no interaction between the inhibitors after laparotomy with intestinal traction. These results show that 1) in addition to B, some aspect of adrenal gland number or mass inhibits the ACTH response to stimuli; and 2) the adrenal number input serves as a marker to distinguish between stimuli to ACTH secretion that are inhibited by B at sites proximal and those that are inhibited by B at sites distal to this input. PMID- 6258444 TI - Nuclear binding of T3 and effects of QO2, Na-K-ATPase, and alpha-GPDH in liver and kidney. AB - Thyroid status was altered by use of a low-iodine-perchlorate (PC) regimen and either reversal with NaI or injections of L-3,5,3'-triiodothyronine (T3). The PC regimen decreased renal and hepatic oxygen consumption (QO2), alpha glycerophosphate dehydrogenase (alpha-GPDH), and Na+-K+-dependent adenosine triphosphatase (Na-K-ATPase) to comparable extents (25 vs. 23%, 26 vs. 39%, and 41 vs. 51%, respectively). Administration of T3 to hypothyroid rats elicited dose dependent increases in hepatic and renal cortical QO2, ouabain-sensitive oxygen consumption (QO2(t)), alpha-GPDH, and Na-K-ATPase activities. The half-maximal increases in all of the response parameters in both kidney and liver were obtained at dosages of 6-32 micrograms T3/100 g body wt. The equivalences in the renal cortical vs. hepatic responses were indicated by correlation coefficients of approximately 0.97. Kidney and liver nuclei also showed similar high-affinity binding of 125I-T3-K1/2 = 29 vs. 18 micrograms T3/100 g body wt, and Nmax = 1.8 vs. 2.1 ng T3/mg DNA. The patterns of the responses plotted as a function of T3 occupancy of the high-affinity nuclear binding sites were indistinguishable in kidney and liver. These results imply similar modes of action of T3, probably initiated at the nuclear level, in both kidney and liver. PMID- 6258445 TI - Hepatic carbohydrate metabolism in the spontaneously diabetic Bio-Breeding Worcester rat. AB - The effects of diabetes on hepatic carbohydrate metabolism were investigated in spontaneously diabetic Bio-Breeding Worcester (BB/W) rats. The juvenile-onset type syndrome displayed by these animals is characterized by beta-cell destruction with subsequent ketosis-prone insulinopenia. Livers from diabetic animals demonstrated increased adenosine 3',5'-cyclic monophosphate levels but subnormal total protein and glycogen content. Isolated perfused livers of diabetic BB/W rats demonstrated an increased rate of glucose production from [14C]lactate and an impaired rate of glycogen synthesis. These data were consonant with hepatic enzyme studies demonstrating markedly increased activities of component gluconeogenic (glucose-6-phosphatase, fructose-1,6-diphosphatase, phosphoenolpyruvate carboxykinase) and glycogenolytic (glycogen phosphorylase) enzymes with decreased activities of glycolytic (hexokinase, pyruvate kinase) and glycogenic (glycogen synthase) enzymes. These findings agree with previous studies using alloxan- and streptozotocin-induced diabetic animals and suggest that accelerated hepatic gluconeogenesis and impaired glucose utilization are pathognomonic of all insulin-deficient diabetic syndromes. PMID- 6258446 TI - Modification of Na and Cl transport in canine tracheal mucosa by prostaglandins. AB - We tested the effect of prostaglandins PGF2 alpha and PGE1 on the transport of 36Cl and 22Na by canine tracheal epithelium. Sheets of epithelium were mounted in Ussing chambers and short-circuited. Addition of PGF2 alpha to the mucosal side resulted in an increase of net Cl secretion from 0.71 +/- 0.41 to 2.40 +/- 0.67 mu eq . cm-2 . h-1 without significant effect on net Na absorption. Prostaglandin E1 on the mucosal side increased net Cl secretion from 1.36 +/- 0.31 to 2.69 +/- 0.35 and decreased Na absorption from 0.87 +/- 0.16 to 0.49 +/- 0.09. Indomethacin significantly depressed net Cl secretion from 1.36 +/- 0.36 to 0.57 +/- 0.22. Subsequent addition of PGE1 augmented net Cl secretion to 3.88 +/- 0.75. PGE1 did not enhance [14C]mannitol fluxes across this epithelium. Cellular levels of cAMP increased in response to PGE1 from 130 +/- 12.7 to 642 +/- 33.4 pmol . mg prot-1 . 10 min-1, whereas PGF2 alpha had no effect. These data suggest that although effects of PGF2 alpha and PGE1 are similar as pertains to net Cl secretion, they differ in their effects on Na transport and their capacity to increase cAMP levels. Alterations in Cl and Na transport in response to PGE1 are likely to be mediated, at least in part, by the adenylate cyclase-cAMP system. Furthermore, endogenous prostaglandins may have an important regulatory role in ion transport by airways epithelium. PMID- 6258447 TI - Characterization of an ATP-dependent Ca2+ uptake system in mouse pancreatic microsomes. AB - The uptake of 45Ca2+ was studied in microsomes prepared from isolated mouse pancreatic acini. These microsomes accumulated 45Ca2+ in the presence of ATP; uptake was potentiated by addition of oxalate. Sequestered microsomal 45Ca2+ was only gradually removed by ethyleneglycol-bis(beta-aminoethylether)-N,N' tetraacetic acid (EGTA) but was readily released by the divalent cation ionophore A23187. Inhibitors of mitochondrial oxidation and mitochondrial calcium transport had little effect on microsomal 45Ca2+ uptake. A separate subcellular fraction enriched in plasma membranes took up 45Ca2+ poorly compared with the microsomal fraction. Half-maximal 45Ca2+ uptake by the microsomal fraction was observed at a free Ca2+ concentration of 1.1 microM. 45Ca2+ uptake was dependent on Mg-ATP and showed a pH optimum at 6.8-7.0. Subfractionation of the total microsomes into "heavy" and "light" microsomal fractions indicated higher 45Ca2+ uptake activity associated with the heavy fraction. A Ca2+-activated, Mg2+-dependent ATPase was demonstrated in this fraction. Stimulation of pancreatic acini with the cholecystokinin analogue caerulein prior to homogenization increased the subsequent rate of 45Ca2+ uptake by the microsomal fraction. PMID- 6258448 TI - Mechanism of propagation of canine migrating motor complex--a reappraisal. AB - This study quantitatively evaluated the characteristics of the aboral propagation of the canine migrating motor complex (MMC). Five conscious dogs were implanted with extraluminal force transducers along the small intestine. After constructing a 30-cm Thirty-Vella loop of jejunum, 56 of 91 activity fronts were outside the tolerance limits for propagation from the proximal intestine to the loop established in the same dogs before operation. Similarly, 44 of 109 activity fronts were outside the tolerance limits for propagation from the loop to the distal intestine. After surgery, the propagation time from the proximal jejunum to the loop was significantly increased, and activity fronts were observed to originate in the loop and in the intestine distal to the anastomosis. Our study indicates that the hypothesis that extrinsic nerves alone control the migration of the MMC is incomplete. We suggest that the extrinsic and the intrinsic innervation of the gastrointestinal tract are both required for the precise pattern of the migration of the MMC. PMID- 6258449 TI - Fluid propulsion by cat intestinal segments under conditions requiring hydrostatic work. AB - The intrinsic ability of duodenal, jejunal, and ileal segments of cats to propel fluid by doing hydrostatic work was investigated in vitro. Segments of terminal ileum demonstrated two functional states. In the net propulsive state, propulsive complexes occurred at an average interval of 7.9 min. These complexes consisted of an initial phase characterized by the simultaneous ejection of equal fluid volumes from both ends of a segment at a frequency of 8/min and a second phase that ejected a net volume of fluid from the aboral end. Ileal segments not in the net propulsive state demonstrated complexes consisting only of the 8/min ejections. Segments of proximal duodenum and midjejunum failed to produce net propulsion when evaluated under similar conditions. These results indicate that 1) ileal segments can intrinsically produce net fluid transport in the aboral direction when hydrostatic work is required for propulsion, 2) propulsive activity intrinsic to ileal segments is regulated by intrinsic control mechanisms having an effective oscillatory period of 8 min, and 3) basic differences exist in the intrinsic control structures between ileal and other intestinal regions. PMID- 6258450 TI - Mucosal gastrin receptor. V. Development in newborn rats. AB - We determined the development of the oxyntic gland mucosal gastrin receptor in rats killed at various times from 5 to 60 days after birth. Rats were weaned on the 18th day after birth. Newborn animals had no detectable gastrin binding, high serum gastrin levels (800-1,200 pg/ml), low antral gastrin levels (0.5-2.0 micrograms/g tissue), or high pH of gastric contents (pH greater than 5.0) and did not respond to pentagastrin. At the time of weaning, serum gastrin dropped to 600 pg/ml and reached adult levels (300 pg/ml) on day 40. Antral gastrin increased to 7.5 micrograms/g tissue on day 20 and reached adult levels (20 micrograms/g tissue) on day 22. Specific binding of gastrin was first detected on day 20 and reached the adult level of 4 fmol/mg protein on day 60. Pentagastrin significantly stimulated acid secretion on day 20 and DNA synthesis on day 25. Prevention of weaning through day 25 decreased the magnitude but did not prevent or delay the onset of the above changes. These results indicate that 1) the absence of a gastrin response in newborn rats is due to a lack of gastrin receptors, 2) development of gastrin receptor and biological sensitivity to gastrin appear at the time of weaning, and 3) the development that occurs with weaning is enhanced but not triggered by the shift to solid food. PMID- 6258451 TI - Evidence for bradykinin potentiation by angiotensin congeners in conscious rats. AB - It has become increasingly clear that the potent vasoactive peptides bradykinin and angiotensin share a common point of metabolism, i.e., angiotensin-converting enzyme or kininase II, and may interact with prostaglandins to regulate regional blood flow. To establish whether the sensitivity to exogenous bradykinin was affected by the presence of angiotensin, vasodepressor dose-response curves to injected bradykinin were performed in conscious rats before and during a 1-h infusion of angiotensin I (30 ng/min), angiotensin II (30 and 300 mg/min), and [Sar2,Ala8]angiotensin II (5 micrograms/min). All of these induced a parallel leftward shift of the bradykinin dose-response curve of approximately threefold. No similar changes were observed during control infusions of dextrose, similar pressor doses of lysine vasopressin, or norepinephrine. Sensitivity to bradykinin was enhanced by saralasin in normal and nephrectomized rats, suggesting that the antagonist itself was responsible. Similar potentiation was present during both acute (1 h) and chronic infusions (9 days) of angiotensin II and attenuated the effect of a converting-enzyme inhibitor on bradykinin sensitivity. Accordingly, these results suggest a competitive interaction in vivo between angiotensin congeners and bradykinin at a point of bradykinin degradation, probably angiotensin-converting enzyme or kininase II. This is a potential additional mechanism by which these systems may interact to affect regional blood flow and must be considered in the interpretation of results obtained during saralasin infusion. PMID- 6258453 TI - Insulinoma: diagnosis, surgical management and long-term follow-up. Review of 41 cases. AB - The clinical features, diagnosis and surgical considerations in 41 patients with insulinoma treated at Columbia-Presbyterian Medical Center are presented along with a review of the literature. One hundred percent of patients surviving surgery for benign functional beta cell tumors were cured of hypoglycemia. A detailed long-term follow-up study in the majority of patients after surgical cure documented a statistically significant incidence of neuropsychiatric aberration, adult-onset diabetes mellitus and peptic ulcer disease. Patients who have undergone surgery for endogenous hyperinsulinism should be followed up carefully for the development of these disorders, and their overall prognosis should be considered cautiously. PMID- 6258452 TI - Adrenergic mechanisms in canine intralobar pulmonary arteries and veins. AB - The responses of canine intralobar pulmonary arteries (IPA) and veins (IPV) to transmural nerve stimulation (TNS), and exogenously administered norepinephrine (NE) were studied to evaluate the alpha-adrenergic neuroeffector system in the canine pulmonary vasculature. IPA and IPV elicited contractions in response to both NE (10(-10) to 10(-5) M) and TNS (0.5-32 Hz, 2 ms duration and delay). The equilibrium (steady state) contractile responses of IPA and IPV to TNS were abolished with the adrenergic neuronal blocking agents guanethidine and bretylium and the depolarization blocking agent tetrodotoxin in concentrations which did not affect the responses to NE or KCl. The contractile responses of IPA and IPV to TNS and NE were reduced in a concentration-dependent way, by the alpha adrenergic receptor-blocking agents phentolamine, tolazoline and clonidine. The contractile responses of IPA and IPV to TNS and NE were enhanced after inhibition of neuronal reuptake of NE (uptake1) with cocaine, as well as after blockade of extraneuronal reuptake of NE (uptake2) with hydrocortisone. Analysis of the equilibrium responses of the IPA and IPV to TNS and NE with an Arunlakshana Schild plot to define the concentration of alpha 1-receptor antagonists necessary to double the ED50 for TNS and NE (defined as the pA2), demonstrated that the postsynaptic alpha-receptors of IPV differed from that of IPA. These data support the conclusions that IPA and IPV 1) contain a functional adrenergic innervation and neuroeffector system, 2) contract in response to both TNS and NE, 3) demonstrate the presence of mechanisms for both uptake1 and uptake2 of NE, and 4) IPV contain postsynaptic alpha-receptors that may differ from each other. PMID- 6258454 TI - An improved method for assaying pyrophosphate exchange measuring Cerenkov radiation. PMID- 6258455 TI - Rapid group separations of nucleotides and related compounds of silica columns. PMID- 6258456 TI - Fast tracer efflux from membrane vesicles; investigation by controlled elution. PMID- 6258457 TI - Rapid purification of covalently closed circular DNAs of bacterial plasmids and animal tumor viruses. PMID- 6258458 TI - Elution of proteins from sodium dodecyl sulfate-polyacrylamide gels, removal of sodium dodecyl sulfate, and renaturation of enzymatic activity: results with sigma subunit of Escherichia coli RNA polymerase, wheat germ DNA topoisomerase, and other enzymes. PMID- 6258459 TI - Halothane effect on cGMP and control of motor activity in mouse cerebellum. AB - The effect of halothane on cerebellar control of motor activity and on cerebellar cyclic 3',5'-guanosine monophosphate (cGMP) content was studied in mice. Isoniazide and picrotoxin were used to increase motor activity and induce seizures associated with an increase in cerebellar cGMP content. Halothane markedly decreased the cerebellar cGMP content (by 60 per cent at 0.61 per cent, the concentration at which 50 per cent of mice lost righting reflex) and prevented the isoniazide-induced increase in cGMP content. Halothane, 0.61 per cent, significantly reduced both isoniazide- and picrotoxin-induced motor activity; the ED50 convulsive dose of isoniazide (137.7 +/- 7.04) and of picrotoxin (1.9 +/- 0.2 mg x kg-1, sc) was about three times higher (402.2 +/- 17.9 and 5.8 +/- 0.6 mg x kg-1, sc, respectively) in mice exposed to halothane. In contrast, halothane did not alter the ED50 convulsive dose of strychnine, which has a different site and mechanism of action, blockade of glycine receptors, a mechanism not involving the cerebellar system. These results indicate that halothane has a significant effect on the cerebellar control of motor activity and that cGMP plays an important role in the alteration of cerebellar function by halothane. PMID- 6258461 TI - Rupture of a giant non-functioning pancreatic islet cell tumor following minimal trauma. AB - The interesting occurrence of a previously asymptomatic giant non-functioning islet cell tumor of the pancreas identified following rupture secondary to relatively insignificant abdominal trauma is reported. Despite the rarity of the condition, this circumstance underscores the need to be aware of the possibility of pre-existing pathology in evaluating and treating patients for blunt abdominal trauma. To our knowledge, this is the first reported instance of this rare disease entity presented secondary to blunt abdominal trauma. PMID- 6258460 TI - [Lymphocytic hormonal receptors (author's transl)]. AB - The recent development of technics of specific fixation using radio isotope labelled tracer elements permits the demonstration of various types of receptors at the level of the lymphocyte membrane. Thus a new route is open in the understanding of the biochemical mechanisms controlling the physiology of the lymphocyte and its role in the immune response. Furthermore these lymphocyte receptors may represent to some degree, the state of the rarely accessible tissue receptors in human pathology. However, at present, the practical interest is limited by the absence of standardisation of technics and the heterogeneity of athe lymphocyte population studied. PMID- 6258462 TI - [Wilms' tumor: a series of 79 cases (author's transl)]. AB - 79 cases of Wilms' tumor with age at diagnosis between 0 and eight years, are reported. 76 of them are evaluable for therapeutic results. 54 (71%) are alive and disease-free, with a mean survival of 53 months. Group A (35 patients) received pre-surgical treatment with radiotherapy and the survival rate is 77%. Group B (32 patients) were not treated before surgery and the survival rate is 84%. Both groups received post-surgical treatment with radiotherapy and chemotherapy (vincristine and actinomycin D). Patients in group C, chronologically the oldest, did not receive chemotherapy and its survival rate was 20%. Prognostical significance of age, sex, site, clinical stage and histology are examined. Classical concepts on histological classifications are revised and present criteria are shown, along with its' therapeutic and prognostic implications. PMID- 6258463 TI - Microfluorometric grading of mammary tumors. A pilot study. AB - Material obtained from 24 women with benign and malignant breast lesions was subjected to comparative morphologic and cytophotometric DNA analysis. All the cases of benign tumors, as well as benign tissue samples obtained from tumor containing breasts, exhibited DNA values corresponding to the diploid control value. The tumors classified as carcinoma in situ or highly differentiated invasive cancers (grade I) showed a distribution of the DNA values significantly different from the diploid control values. The tumors classified s grade II and III showed a shift to the "triploid" area or were totally aneuploid. The results of the present pilot study suggest that quantitative cytophotometric DNA analysis can be used for grading the malignancy of breast tumors in combination with conventional histologic examination. Additional studies of larger groups of women may yield further information on the microfluorometric grading of malignancy. Such studies may also contribute to the further development and use of automated methods of cytologic diagnosis. PMID- 6258465 TI - [Repercussions of prolonged ingestion of dieldrin on digestibility of nutrients and nitrogen balance in the quail]. AB - The presence of organochlorated pesticides in foods intended for animal and human consumption is on one hand a real fact and on the other hand, it is known that they could alter some enzymes activities and, consequently, modify, at a larger or lesser extent, the metabolic pathways where they are implicated. According to this, it seemed interesting to study the influence of one of such molecules, dieldrin, on nutrients utilization. The work was carried out on adult quails (Coturnix coturnix japonica) of both sexes; 20 ppm, were mixed in their diets, during a period of 48 days. Dieldrin does not affect food intake in both sexes, but produces a significant weight decrease in the males. Nutritive utilization of protein, judged by digestibility coefficient and nitrogen balance do not suffered any alterations. Furthermore, dieldrin does not affect carbohydrate utilization (nitrogen free extract) and raw fiber. On the contary, fat digestibility decreased in pesticide treated males and was not altered in females and this effect dependend upon the exposition time to the contaminant. PMID- 6258464 TI - Toxic shock syndrome in menstruating women. AB - Eight adult women became severely ill with an acute, toxic erythroderma during menses. The syndrome was characterized by fever, generalized erythema, profound shock, multiple organ dysfunction, and desquamation occurring several days after the rash had faded. Gastrointestinal and cardiovascular abnormalities were present in all patients; three patients required ventilatory support; dialysis was performed on two; and one patient died. Mild relapse occurred in two patients during subsequent menses; the other patients have recovered without sequelae during follow-up of 6 to 42 months. Cervical colonization or local infection with Staphylococcus aureus is associated with this syndrome. PMID- 6258467 TI - Familial multiple glomus tumors and pheochromocytomas. AB - Isolated cases of cervical cranial glomus tumors have been reported in association with pheochromocytoma. Two family pedigrees are presented and four individual cases discussed indicating a hereditary syndrome of pheochromocytoma associated with multiple glomus tumors of the head and neck. The hereditary potential has not previously been described. In three of the patients, the pheochromocytomas were asymptomatic at the time of initial presentation. These pheochromocytomas were discovered by arteriography after one of the patients developed a hypertensive crisis with the induction of anesthesia. The silent presence of pheochromocytomas in patients with multiple glomus tumors should be considered in the evaluation of these patients. PMID- 6258468 TI - Tumors of the parapharyngeal space: preoperative evaluation, diagnosis and surgical approaches. AB - This report demonstrates that preoperatively the radiologist can provide the surgeon with the size, extent, origin and probable histology of a parapharyngeal space tumor. Using this information, the surgeon can then determine the best surgical approach for complete and safe tumor excision. PMID- 6258466 TI - [Tomodensitometry and/or meato-isternography in the diagnosis of small acoustic neuromas (author's transl)]. AB - Tomodensitometry allowed us to discover smaller and smaller tumors in the cistern and even in the internal auditory canal. We report 5 cases, amongst others, where the tumor is visible in the canal and we show the conditions which are necessary to make the diagnosis. Nevertheless, lipiode meatocisternography is well tolerated if we use between 0.6 and 1.5 ml of oil, and often necessary to confirm the diagnosis of a neuroma. We first use tomodensitometry when the symptoms could be due to a neuroma or another tumor. When the syndrome is characteristic, limited to the contents of the internal auditory canal, we often do the meatocisternography straight away, because in a single examination we know that there is or is not a tumor. We can also check the same time the opposite side. PMID- 6258469 TI - Nephroblastoma and Beckwith-Wiedemann syndrome. PMID- 6258470 TI - [Primary linitis plastica carcinoma of the colon and the rectum. Report of three personal cases (author's transl)]. PMID- 6258471 TI - Survival of enteroviruses in rapid-infiltration basins during the land application of wastewater. AB - The downward migration through soil of seeded poliovirus type 1 and echovirus type 1 and of naturally occurring enteroviruses during infiltration of sewage effluent through rapid-infiltration basins was investigated. After 5 days of flooding, the amount of seeded poliovirus type 1 that had migrated 5 to 10 cm downward through the soil profile was found to be 11% of that remaining at the initial burial depth. The amount of echovirus type 1 determined to have moved an equal distance was at least 100-fold less. Migration of naturally occurring enteroviruses during infiltration of sewage effluent through soil could not be measured with accuracy because of the possibility of virus survival from previous applications of effluent. The rate of inactivation for seeded poliovirus 1 and echovirus 1 buried in the infiltration basins ranged between 0.04 and 0.15 log10 units per day during the time when the basins were flooded. Inactivation of these same seeded virus types and of indigenous enterovirus populations in the infiltration basins during the drying portion of the sewage application cycle ranged between 0.11 and 0.52 log10 units per day. The rate of virus inactivation was dependent upon the rate of soil moisture loss. These results indicate that drying cycles during the land application of wastewater enhance virus inactivation in the soil. PMID- 6258472 TI - Poliovirus concentration from tap water with electropositive adsorbent filters. AB - Simple, reliable, and efficient concentration of poliovirus from tap water was obtained with two types of electropositive filter media, one of which is available in the form of a pleated cartridge filter (Virozorb 1MDS). Virus adsorption from tap water between pH 3.5 and 7.5 was more efficient with electropositive filters than with Filterite filters. Elution of adsorbed viruses was more efficient with beef extract in glycine, pH 9.5, than with glycine-NaOH, pH 11.0. In paired comparative studies, electropositive filters, with adsorption at pH 7.5 and no added polyvalent cation salts, gave less variable virus concentration efficiencies than did Filterite filters with adsorption at pH 3.5 plus added MgCl2. Recovery of poliovirus from 1,000-liter tap water volumes was approximately 30% efficient with both Virozorb 1MDS and Filterite pleated cartridge filters, but the former were much simpler to use. The virus adsorption behavior of these filters appears to be related to their surface charge properties, with more electropositive filters giving more efficient virus adsorption from tap water at higher pH levels. PMID- 6258473 TI - Comparative inactivation of viruses by chlorine. AB - The kinetics of inactivation of six enteric viruses plus simian virus 40 and Kilham rat virus by free available chlorine was studied under carefully controlled laboratory conditions. It was found that the different virus types demonstrated a wide range of susceptibility to chlorine disinfection. The rate of inactivation was greater at pH 6 than at pH 10; however, the relative susceptibilities of the different viruses were affected differently by a change in pH, suggesting that the pH influenced both the species of chlorine present and the susceptibility of the different viruses to chlorine. The presence of potassium chloride also affected the susceptibility of viruses to chlorine. PMID- 6258475 TI - Thermostabilization of enteroviruses by estuarine sediment. AB - The effect of estuarine sediment on the thermoinactivation of poliovirus type 1 and echovirus type 1 was evaluated. Poliovirus survival was prolonged at 24 and 37 degrees C but not at 4 degrees C in the presence of sediment over the time periods observed. Further inactivation studies were performed at 50 and 55 degrees C to maximize the thermal effects, and similar protection was observed. The supernatant fluid from a mixture of seawater and sediment lacked the protective effect against thermoinactivation, suggesting that prolonged virus survival in the presence of sediment was due to adsorption to particulates. From these observations, it appears that the adsorption of enteroviruses to estuarine sediments may play a significant role in protecting them against thermoinactivation. PMID- 6258474 TI - Investigation of Salmonella infection in goats fed corn silage grown on land fertilized with sewage sludge. AB - A total of 36 goats were fed for 17 months with corn silage grown on land fertilized with human sewage sludge. These animals were investigated for salmonella infections. Salmonellae were not detected in cultures of fecal or silage samples. No significant agglutination titers were detected in goat sera examined. Salmonella newport C2 was isolated from the sludge used as fertilizer on the cornfields. The public health aspects of the findings are discussed as they relate to the increasing use of sewage sludge for agricultural fertilizers, as well as to the resultant effects on human food and livestock feed. PMID- 6258476 TI - Inactivation of poliovirus I (Brunhilde) single particles by chlorine in water. AB - Like the Mahoney strain, the Brunhilde strain of poliovirus aggregated slowly in dilute phosphate-carbonate buffer at pH 6 but not at all at or above pH 7. Infectivity decreased at rates approximately proportional to the concentration of free chlorine present at pH 6 over the entire range of 5 to 40 micrometer. The addition of 0.1 M NaCl to the buffer increased the rate about twofold, but this strain was still twice as resistant as the Mahoney strain. At pH 10, inactivation was much slower than at pH 6, but when 0.1 M NaCl was added, the rate was increased 31-fold, making the OCl- at pH 10 over three times more effective than HOCl at pH 6. PMID- 6258478 TI - Concentration of poliovirus in water by molecular filtration. AB - The efficiency of concentrating poliovirus 1 from distilled water samples was determined by using a recirculating-flow molecular filtration system. The most efficient recoveries were achieved against members with a 10,000 nominal molecular weight limit pretreated with flocculated beef extract. This procedure yielded a mean virus recovery of 67%. PMID- 6258477 TI - Recovery of indigenous viruses from wastewater sludges, using a bentonite concentration procedure. AB - A distilled water elution-bentonite concentration technique was developed and used to monitor indigenous viruses present in liquid sludges undergoing land application at six field sites. PMID- 6258479 TI - Laminin-like glycoproteins in extracellular matrix of endodermal cells. PMID- 6258480 TI - Selective modification of rabbit liver fructose bisphosphatase. PMID- 6258481 TI - Ethylene from 2-keto-4-thiomethyl butyric acid: the Haber-Weiss reaction. PMID- 6258482 TI - Modification of oligosaccharide-lipid synthesis and protein glycosylation in glucose-deprived cells. PMID- 6258483 TI - Purification and characterization of calmodulin from porcine renal medulla. PMID- 6258484 TI - Opioid hexapeptides and heptapeptides in adrenal medulla and brain possible implications on the biosynthesis of enkephalins. PMID- 6258485 TI - Pathology quiz case 2. Multiple glomus tumors. PMID- 6258486 TI - Antibodies to Herpesvirus hominis types 1 and 2 in malnourished Nigerian children. AB - Antibodies to Herpesvirus hominis (HVH) types 1 and 2 were determined by a micro neutralisation method in 37 children with kwashiorkor, 16 with marasmus, and in 64 well-nourished control children. All the children were aged between 1 and 4 years. The prevalence of antibodies was similar in the two sexes and at different ages. HVH-1 antibodies were present in 51% of children with kwashiorkor, in 44% with marasmus, and in 26% of well-nourished children, reflecting the very poor socioeconomic conditions of malnourished children. HVH-2 antibodies too were present in about 19% of children with kwashiorkor, and in 2% of well-nourished controls; they were absent in marasmic children. It is suggested that HVH-2 infection in malnourished children is facilitated by the communal use of fomites- such as bedclothes and underwear. PMID- 6258487 TI - Primary Epstein-Barr virus infection in early childhood. AB - In a prospective study 43 consecutive children in hospital, aged between 6 months and 7 years and displaying at least one of the clinical signs of infectious mononucleosis (IM), were investigated for Epstein-Barr (EB) virus-specific IgM antibodies by an indirect immunofluorescence test. On this basis EB virus infection was considered confirmed in 8 patients, each of whom had IgM antibodies in the initial serum sample. In one additional patient, IgM antibodies were only detected in a second sample. The IgM antibodies disappeared with 3-11 weeks. Assessment of IgG antibodies had no diagnostic value in the acute phase of IM. Clinically the 3 youngest children, about 1 year of age, were diagnosed as having pneumonia or hepatitis, the 5 other consecutive patients as having IM. Hepatosplenomegaly was fairly frequently associated with IM, while sore throat, lymphadenopathy, and rash were often signs of other diseases. Only the oldest child had heterophil antibodies. Atypical lymphocytes (greater than 10%) were present in 4 of the 9 IM cases and were seen in children with other diseases as well. Our data stress the importance of measuring EB virus-specific IgM antibodies in order to diagnose IM in early childhood. PMID- 6258488 TI - Treatment of hypophosphataemic vitamin D-resistant rickets. PMID- 6258489 TI - Plasma 25-hydroxyvitamin D concentrations in preterm infants receiving oral vitamin D supplements. AB - Plasma 25-hydroxy-cholecalciferol (25-OHD) was measured serially in two groups of preterm infants receiving either 400 IU or 1000 IU oral vitamin D3 daily. All the babies were able to absorb and hydroxylate vitamin D3 adequately by 36 weeks' gestational age. The higher daily supplement had no advantage over the lower dose. PMID- 6258491 TI - [Juvenile nasopharyngeal angiofibroma: ultrastructural study (author's transl)]. PMID- 6258490 TI - Polybrominated biphenyl congener levels and distribution patterns in raw and cooked beef. AB - The retention and distribution of eight polybrominated biphenyl (PBB) congeners were studied by roasting beef sirloin tip samples to an internal temperature of 65 degrees C, braising and broiling adductor and semimembranosus steaks to an internal temperature of 77 degrees C, broiling ground round and hamburger patties 77 degrees C, and comparing cooked values with those in the raw. Rounds were obtained from four Holstein cows with known PBB contamination. Significant reductions in PBBs occurred with cooking of all cuts. Roasting sirloin tips reduced the PBBs by 45.7%. Broiling reduced PBBs as follows: Adductor steaks (53.2%), semimembranosus steaks (71.2%), ground beef patties (32.3%) and hamburger patties (31.5%). Braising reduced PBBs in the adductor steaks by 37.2% and in the semimembranosus steaks by 34.9%. The distribution of PBB congeners was also affected by cooking in all cuts except hamburger. The proportion of 2,4,5,2',4',5'-hexabromobiphenyl decreased upon cooking but the change in the proportion of 2,3,4,5,2',4',5'-hepatbromobiphenyl varied with the cut used. Both of these isomers are known to be phenobarbital type inducers. The proportion of 2,4,5,3',4'5'-hexabromobiphenyl, which both a 3-methylcholanthrene and phenobarbital type inducer, increased in the roasted sirloin tip surface and broiled ground round patties. PMID- 6258492 TI - [Gangliocytic paraganglioma of the duodenum: report of one case (author's transl)]. PMID- 6258495 TI - [Venous thrombosis in the portal venous system and liver cirrhosis. Paraneoplastic syndrome? (author's transl)]. PMID- 6258493 TI - [Nephronogenic nephroma (author's transl)]. PMID- 6258494 TI - [Adenocarcinoma of the stomach]. PMID- 6258496 TI - [Tracheal glomus tumour (author's transl)]. PMID- 6258497 TI - Protozoal infection in human beings in India. A critical review of the literature. PMID- 6258498 TI - [Prevalence of antibody to hepatitis A virus in healthy Umbrian population (author's transl)]. PMID- 6258499 TI - A radionuclide study on the effectiveness of drainage after elective cholecystectomy. AB - Passive drainage after elective cholecystectomy was studied in six patients. Their erythrocytes were labeled in vitro with technetium-99mTc and injected via the drain after operation. After one hour, we were able to recover labeled erythrocytes and free pertechnetate from peripheral blood. After 24 hours, a large part of the injected erythrocytes had been evacuated via the drain. In eight patients subjected to cholecystectomy, 99mTc-HIDA was injected intravenously after the operation. In four cases, in which the gallbladder bed was raw, the activity ratio discharge/blood rapidly reached extremely high values. In the other four cases, in which the liver surface had not been denuded, the ratio was much lower. Passive drainage is a useful device for evacuation intra-abdominal bile or hemolysed blood after cholecystectomy, especially when the gallbladder bed has been denuded. PMID- 6258501 TI - Chemotherapy of Trypanosoma venezuelense (T. evansi), I. Activity of trivalent antimonials in mice by long and short term tests. PMID- 6258502 TI - Small cell carcinoma of the lung. AB - Prospects for the patient with small cell carcinoma of the lung have been partially turned around during the past decade. This dramatic achievement remains very incomplete, but it continues to gather momentum and seems to carry promise of greater advance in the future. An essential feature of the new approach to treatment is that it depends on cooperative and interdisciplinary effort; in all probability, increasing cooperation will be necessary for future progress. We will attempt to review here the current approaches to the understanding and management of this disease, as they may be of concern to surgeons, and to try to define the areas of failure and controversy. PMID- 6258500 TI - Nonfunctioning islet cell tumors. AB - In nonfunctioning islet cell tumors of the pancreas, hormone production is not clinically evident. This type of tumor constituted 15% of all islet cell tumors seen at the Mayo Clinic from 1960 through 1978. Although identical to functioning islet cell tumors embryologically and histologically, the nonfunctioning tumors differ in presentation, location, size, and rate of malignancy. At admission to the hospital, patients often have pain or jaundice due to a large, solid, solitary lesion that occurs most commonly in the head of the pancreas. Extended survival is not excluded by the high malignancy rate (92%) of these slow-growing tumors. The survival rates at three and five years were 60% and 44%, respectively, even though most patients had metastatic disease at the time of exploration. PMID- 6258503 TI - A lectin activity in Entamoeba histolytica trophozoites. AB - A lectin (carbohydrate binding protein) has been found in extracts of a number of axenically grown trophozoites of Entamoeba histolytica strains. The strains grown in Diamond's TYI-S-33 media were HK-9, 200:NIH and HM-1: IMSS. Strain HU-1: MUSC (HSC) was grown monoxenically in the same medium. The amoeba lectin agglutinates glutaraldehyde-fixed red blood cells. This activity is pH dependent, heat and oxidation sensitive and is destroyed by proteolysis upon auto-incubation. The relative agglutinating potency of the different strains was investigated. Strain HSC had the highest specific activity (210 units/mg protein) and strain HM-1 the lowest (14 units/mg). One unit of haemagglutinating activity is defined as the amount of leetin present in 1 ml of extract which will agglutinate 1 ml of 4 per cent red blood cells. Upon subcellular fractionation of the lectin present in extracts of strain HK-9, two thirds of the activity were detected in the soluble, non-sedimentable (100,000 x g, 60 min) fraction. Partial hydrolysate of chitin was found to inhibit the haemagglutinating activity. Among the oligosaccharides of N-acetylglucosamine, the trimer and tetramer were the most potent inhibitors. The lectin was purified approximately 300 fold by a one step affinity chromatography on a chitin column. The loading and elution from the column were based on the pH dependence of the lectin activity. PMID- 6258504 TI - Serum proteins in the plasma membrane of Entamoeba histolytica. AB - The ability of axenic Entamoeba histolytica, strain 200:NIH, to adsorb serum proteins was studied. Amebae were grown in Diamond's TPS-1 medium. Serological reactivity was observed between the plasma membrane of E. histolytica and rabbit anti-bovine or anti-human serum when the amebae were grown, respectively, with bovine or human serum. Antisera were obtained from rabbits immunized with culture medium, amebal homogenates, and various amebal subcellular fractions: soluble phase, microsomal fraction, and a large vesicle fraction. The presence of serum proteins was demonstrated in the large vesicle fraction by the double diffusion and indirect hemagglutination tests. Immunofluorescence (IF) studies on amebae grown in bovine or human serum showed the surface amebae exhibited IF with specific antibodies against the serum in which they were grown. Rabbit anti-human serum blocked IF on the surface of amebae grown with human serum. From these data we conclude that the plasma membrane of in vitro grown E. histolytica can adsorb human and bovine serum proteins. PMID- 6258505 TI - Studies on the cytopathogenicity of Entamoeba histolytica. AB - We have explored the interaction of virulent and avirulent E. histolytica (HM1 and 303 respectively) with human polymorphonuclear leukocytes (PMNs) and Chinese hamster ovary (CHO) cells. PMNs exhibit chemotaxis to both HMl and 303. On contact with HMl, PMNs degranulate and die (trypan blue uptake); incubation at a ratio of 100 PMNs per ameba for 40 minutes revealed 70 per cent PMN death with 84 per cent HMl viability. 303s are often ingested by PMNs on contact; after incubation as above, only 1 per cent of 303 were intact with PMN mortality equaling that of control. HMl leukotoxicity occurred under anaerobic conditions, in immune serum, and was not mediated by complement. CHO cells are disrupted by HMls, less than 50 per cent of CHO monolayer remains after < 3 hours with 10(4) HMl/ml. Sonicated HMls (.5 x 10(5)/ml) washed in phosphate buffered saline caused cell release without cell death versus control (by trypan blue uptake). When 5 microgram/ml of Cytochalasin B was added to PMNs and CHO cells, cytopathogenicity by HMls decreased 62 per cent (p < .01) and nearly to control values (p < .01) respectively. Colchicine 0.25 mM had no significant effect on PMN cytopathogenicity. Washed HMl and 303 (1 x 10(5)/ml) were agglutinated by 10 microgram/ml and 100 microgram/ml of the lectin concanavalin A. Cytopathogenicity was associated with intact microfilament function and ameba motility. Surface membrane receptors may be important mediators of virulence. Further studies of potential membrane receptors and inhibitors are underway. PMID- 6258507 TI - Serum-inhibited toxicity of Entamoeba histolytica. AB - The cytopathogenic effect (CPD) of soluble antigens prepared from various strains of Entamoeba histolytica, differing in virulence, was assayed on monolayers of baby hamster kidney cells growing in microtiter plates. Serum-inhibited toxicity could be detected in all these strains and in E. invadens, but not in the Huff strain and in an Acanthamoeba species. Gel chromatography demonstrated a peak activity of the toxin in a fraction with M.W. between 35,000 and 45,000. Other experiments learned that the toxin is a heat-labile glycoprotein, stable between pH 4 and 10, degradable by trypsin, dependent in its activity on sulphydryl goups, and inhibited by anti-E. histolytica IgG and nonimmune serum factors with a M.W. between 50,000 and 100,000. It is also excreted by the ameba and this may explain the effect of serum on contact lysis, induced by intact amebae on BHK cells. PMID- 6258506 TI - Further studies on a cytotoxin/enterotoxin from Entamoeba histolytica. AB - More virulent strains of Entamoeba histolytica contain more cytotoxic activity per trophozoite than do less virulent strains. Clarified sonicates of the more virulent strains are more cytotoxic than those of less virulent strains. The cytotoxins of all these strains are inhibited by specific immune IgG raised in rabbits or produced by natural human infection. Non-immune IgG's had no antitoxic activity. Serum fractions of non-immune serum containing alpha globulins (alpha 2 macroglobulin and alpha 1 antitrypsin) had a non-specific inhibitory effect on the cytotoxicity of the E. histolytica toxin. The positive correlation of strain cytotoxicity and the amount of toxin per trophozoite, with virulence suggests that the cytotoxin could play a role in production of human disease. The presence of immunoglobulins against the toxin in serum from a patient with clinical amebiasis indicates that the toxin is immunogenic in human infections and provides additional support for the relevance of E. histolytica cytotoxin to pathogenesis. PMID- 6258508 TI - Detection of antibodies against lectin-like "toxin" of Entamoeba histolytica in sera of patients with invasive amebiasis. PMID- 6258509 TI - [Effect of Entamoeba histolytica on the chemotaxis of human monocytes]. PMID- 6258510 TI - [Virulence and surface properties of various axenic strains of Entamoeba histolytica]. PMID- 6258511 TI - [Specific proteins and culture media proteins found in trophozoites of E. histolytica obtained by axenic cultivation]. PMID- 6258512 TI - Sequential histopathology of cavitary liver abscess formation induced by axenically grown Entamoeba histolytica. AB - Animal models of amebic hepatic abscess should parallel the human disease. Experimental amebic hepatic abscess in the hamster results in granulomatous lesions during the early period (six days) following inoculation. Hamster inoculated intrahepatically with axenically grown, non-liver passaged strains of Entamoeba histolytica revealed no evidence of lesions when sacrificed at later times. However, hamsters similarly inoculated with multiply liver passaged substrains were found to have large fluid-filled hepatic abscesses four to six weeks following inoculation. The histopathologic appearance of these lesions closely resembled that most often described in human amebic hepatic abscess. Production of amebic hepatic abscess in the hamster may provide a valuable animal model of this potentially fatal human disease and provide new information concerning both the pathogenesis and host response. PMID- 6258513 TI - [Development of lesions produced in hamsters by inoculation of Entamoeba histolytica]. PMID- 6258514 TI - [Histochemistry of the hepatic lesion produced in hamsters by inoculation with E. histolytica from axenic cultures]. PMID- 6258515 TI - [Participation of T lymphocytes in the anti-Entamoeba histolytica immune response in hamsters]. PMID- 6258516 TI - [Decreased activity of the mononuclear phagocytic system in hamsters infected with Entamoeba histolytica]. PMID- 6258517 TI - Loss of susceptibility to antibody and complement mediated lysis in E. histolytica. PMID- 6258518 TI - [Induction of immunity to amebiasis in subhuman primates by lysosomal antigen of Entamoeba histolytica. I. Introduction]. PMID- 6258519 TI - [Induction of immunity to amebiasis in subhuman primates by lysosomal antigen of E. histolytica. II. Isolation and characteristics of lysosomal antigen]. PMID- 6258520 TI - [Induction of immunity to amebiasis in subhuman primates by lysosomal antigen of Entamoeba histolytica. III. Counterimmunoelectrophoresis and indirect hemagglutination reactions in monkey serum]. PMID- 6258522 TI - [Induction of immunity to amebiasis in subhuman primates by lysosomal antigen of Entamoeba histolytica. V. Intradermal reactions with histolyticin in monkeys]. PMID- 6258521 TI - [Induction of immunity to amebiasis in subhuman primates by lysosomal antigen of Entamoeba histolytica. IV. Cytopathogenic effect of monkey serum on trophozoites of Entamoeba histolytica]. PMID- 6258523 TI - [Induction of immunity to amebiasis in subhuman primates by lysosomal antigen of Entamoeba histolytica. VI. Intrahepatic inoculation of virulent E. histolytica in monkeys]. PMID- 6258524 TI - [Induction of immunity to amebiasis in subhuman primates by lysosomal antigen of Entamoeba histolytica. VII. Comments and conclusions]. PMID- 6258525 TI - [Diagnostic and therapeutic evaluation of invasive intestinal amebiasis in children]. PMID- 6258526 TI - Isolation of the plasma membrane of Entamoeba histolytica. PMID- 6258527 TI - Axenic cultivation of Entamoeba histolytica: progress and problems. AB - Eighteen years of technological progress in the field of axenic cultivation of Entamoeba histolytica is reviewed. During this period cumbersome diphasic media gave way to easily prepared clear liquid media. Yields of amebae were increased a thousand fold, and doubling time reduced from 24 to less than 8 hours. Attention is directed to three problems, any one of whose solution will extend the potencial of the axenic cultures. They are 1) to develop a defined medium, 2) to reduce the interval between isolation of the amebae from the host and their establishment in axenic culture, thus lessening the opportunity for selection and/or mutation to occur during a period of high risk, 3) to develop a method whereby the entire life cycle of E. histolytica, and not merely cultivation of the trophic form, can be realized under axenic conditions. PMID- 6258528 TI - Dynamic changes on the surface of Entamoeba induced by antibodies. AB - Antibody and Concanavalin A bound to the cell surface of Entamoeba induced segregation of these complexes towards the uroid, followed by an evagination of the membrane portion that contained the components redistributed. This vesiculated cap was released into the medium. Con A polarized all Con A-binding glycoproteins from the surface of the ameba while with antibodies only some of the surface antigens were movilized towards the cap area. This phenomenon was temperature dependent as shown in E. invadens. It was also shown that most of surface antigens that form the cap could not be removed from the cell by proteolysis, suggesting that they were tightly bound to plasma membrane. The interest to define the process of capping in Entamoeba, is because its unique fashion to loss a portion of plasma membrane, and to determine if this phenomenon is related with the ability of ameba to outcome immune injury. PMID- 6258529 TI - Role of iron-sulfur proteins in the electron transport system of Entamoeba histolytica. PMID- 6258530 TI - Purine nucleotide synthesis in Entamoeba histolytica: a preliminary study. AB - Entamoeba histolytica, axenically grown, were unable to incorporate 14C-glycine into extractable purines, even after 16 hours incubation in the presence of this compound. Similarly, amoebas did not incorporate 14C-sodium formate into purines. Such data indicate a total absence of a de novo purine biosynthetic pathway in this amoeba. When amoebas were incubated in the presence of 3H-adenine and 3H adenosine for one hour, considerable radioactivity was associated with AMP, ADP and ATP; no appreciable radioactivity was recoverable in the various guanine residues. However, after 16 hours incubation, a small percentage of guanine derivatives were labelled. Amoebas incubated for similar time periods in medium containing 3H-guanosine yielded high levels of radioactive guanosine and guanine nucleotides after one hour, and 3H-guanosine was not converted to adenine derivatives; after 16 hours incubation some 3H-guanosine was converted to adenine derivatives. PMID- 6258531 TI - [Transfer ribonucleic acids of Entamoeba histolytica. I. Chromatographic analysis of the tRNA isoacceptor species of trophozoites]. PMID- 6258532 TI - Physico-chemical factors affecting the behaviour and activity of Entamoeba histolytica. AB - Activity of individual trophozoites of several strains of axenic Entamoeba histolytica under different environmental conditions was measured by means of a newly devised method. Activity was found to be different between strains and corresponded to the degree of their pathogenicity. At low pH values amoebae moved further due to a straightening of their paths. A similar phenomenon was found in 1:50 cilution of pig bile. Bile was also found to induce an increase in the number of monopodial, "limax-like" forms in proportion to its concentration. PMID- 6258533 TI - Inhibitory action of vagal nerve and spinal cord afferents on discharge pattern of bulbar respiratory modulated neurons. AB - Single vagal nerve stimuli delivered during burst discharge of respiratory modulated neurons entailed lengthening of an interspike interval in 37% of all units tested. Occasionally stimuli delivered to the spinal cord caused lengthening of interspike intervals in respiratory modulated neurons and in other bulbar units the discharge of which was not modulated with respiration. Vagal stimuli often entailed lengthening of the following interspike interval, while the interval during which stimuli were applied remained unaltered; latencies suggested that inhibitory pathways were polysynaptic. In expiratory-inspiratory (EI) and inspiratory (I) neurons, lengthenings of intervals roughly doubled those noted in inspiratory-expiratory (IE) and expiratory (E) units. Lengthening of intervals depended on stimulus incidence within the intervals and was greatest when stimuli were delivered during the late part of the intervals. In EI and I units, lengthening of intervals occurred mainly during the middle part of burst discharge, in IE and E neurons, however, towards the end of the burst. Conditioning of discharge of respiratory modulated neurons could be demonstrated. PMID- 6258534 TI - [Autoantibodies in glioblastoma multiforme (author's transl)]. PMID- 6258535 TI - [Surgical excision of a hepatoma complicating chronic tyrosinemia (author's transl)]. AB - A girl with chronic hereditary tyrosinemia is described in whom the diet caused an immediate resolution of tubular defect and rapid healing of the rickets. However cirrhosis was not prevented and at the age of 8 she developed a hepatoma. Complete surgical excision was possible and she remained well 15 months later. The value of blood alpha-fetoprotein levels and liver echotomography to monitor the course of the disease is emphasized. The apparent ineffectiveness of the low phenylalanine and tyrosine diet in preventing hepatic complications is discussed. PMID- 6258536 TI - Computed tomographic mammography. Diagnosis of mammographically and clinically occult carcinoma of the breast. AB - If breast cancer can be detected early, while it is still localized and before it can be palpated, the prognosis for cure is excellent. Heretofore, conventional mammography has been the only means available to detect cancer at such an early stage. Two cases of minimal breast carcinoma measuring less than 5 mm in diameter have been detected and correctly diagnosed using computed tomographic mammography (CT/M). Both cases occurred in fatty breasts and were clinically and mammographically occult. These cases demonstrate the value of CT/M in the diagnosis of minimal breast carcinoma that would have been missed otherwise. PMID- 6258537 TI - Surgical management of ovarian cancer. AB - Ovarian cancer represents the second most common cancer of the female reproductive organs. It is usually not associated with significant warning signals that led to early diagnosis. The management is based on adequate surgical staging, removal of as much of the bulk tumor as possible, careful histologic assessment of the primary cancer and its metastases, and appropriate postoperative adjuvant therapy. Stage I cancer confined to one ovary and with a very favorable histology, such as borderline malignant epithelial cancers, dysgerminoma, granulosa cell tumor, and Sertoli-Leydig's cell tumor, may be treated with surgery alone. Stage I epithelial cancers are best treated with a total abdominal hysterectomy, bilateral salpingo-oophorectomy, and adjuvant chemotherapy or radiation therapy. Stage I nonepithelial malignant neoplasms are best treated with a unilateral salpingo-oophorectomy followed by an aggressive combination chemotherapy. Advanced ovarian cancers regardless of the histologic origin of the tissue should be treated with aggressive surgery, including complete removal of the tumor whenever possible followed by adjuvant therapy selected on the basis of the histologic appearance of the tumor. Complete remissions for ovarian cancer should be confirmed by second-look operation prior to discontinuing adjuvant chemotherapy. PMID- 6258538 TI - Estradiol receptor-binding protein in head and neck neoplastic and normal tissue. AB - Estradiol (E2) receptor-binding protein was measured in 42 neoplasms and normal tissues from the head and neck region. Tissues with high E2 receptor protein content included normal skin and normal mucosa of the nose and the floor of the mouth and of the parotid and submandibular salivary glands. Two of four papillary carcinomas of the thyroid, three of five pleomorphic adenomas of the parotid, four of six squamous cell carcinomas of the oral cavity, one of angiofibroma of the nose, and an eye (sclera) melanoma also had a high content of E2-binding protein. The demonstration of estrogen receptors in these neoplasms may indicate that these tumors also, as many breast lesions, may be hormone-dependent. If this is correct, an appropriate hormonal treatment may influence their biological evolution. PMID- 6258539 TI - Percutaneous transhepatic pancreatic vein catheterization in localization of insulinoma. AB - Localization of pancreatic insulinomas can present considerable operative difficulty. Blind pancreatic resections are likely to miss the tumor and are associated with the concomitant morbidity and mortality of repeated explorations and resections. While arteriography is often very helpful in locating the tumor preoperatively, there are some patients in whom a tumor blush cannot be seen. The use of percutaneous transhepatic pancreatic vein sampling for radioimmune insulin assay is reviewed, with particular emphasis on its usefulness in locating a small insulinoma. The technique is readily adaptable to other endocrine-secreting tumors of the pancreas. PMID- 6258541 TI - State of the art review: adrenergic bronchodilators. PMID- 6258540 TI - Demonstration by immunofluorescence that the same cells from chick embryo aortas synthesize elastin and collagen types I and III. AB - Cells were isolated from the aortas of 17-day old chick embryos and they were stained with fluorescent antibodies specific for Type I collagen, Type I procollagen, Type III collagen, elastin and prolyl hydroxylase. The results indicated that the same cells simultaneously synthesize Type I procollagen, Type III procollagen and elastin. The synthesis of procollagens, and the presence of prolyl hydroxylase, in the same cells which synthesize elastin may well explain why elastin contains hydroxy-proline. PMID- 6258542 TI - Fisher's syndrome associated with Epstein-Barr virus. PMID- 6258543 TI - CSF polyamines. Potential as brain tumor markers. AB - The use of CSF polyamine levels for the detection of brain tumors is discussed, with special emphasis on the use of CSF polyamine levels for the diagnosis and care of patients with medulloblastoma. PMID- 6258544 TI - Amiodarone keratopathy: drug-induced lipid storage disease. AB - Therapeutic administration of amiodarone, an antiarrhythmic drug, to eight patients resulted in the formation of vortex-like figures within the anterior cornea. Clinical examination disclosed no visual loss or other ocular abnormality attributable to the drug. In one patient, light and transmission electron microscopy of corneal epithelium, bulbar conjunctiva, and cataractous lens revealed complex lipid deposits within lysosome-like intracytoplasmic inclusions in corneal, conjunctival, and lens epithelium, conjunctival fibrocytes, and conjunctival vascular endothelium. Amiodarone keratopathy is compared clinically and morphologically with the corneal alterations seen in Fabry's disease and in chloroquine use as an example of a drug-induced lipid storage disorder. PMID- 6258545 TI - Vitamin A in experimental herpetic keratitis. AB - Systemic vitamin A palmitate at three dosage levels was evaluated for its effect on experimental herpes simplex virus (HSV) keratitis in corticosteroid-treated rabbits. High-dose vitamin A palmitate reduced the severity of herpetic keratitis, but the low or moderate doses did not, and none of the vitamin A treatments affected virus recovery. Vitamin A treatment, however, produced substantial weight loss in uninfected rabbits and in corticosteroid-treated, HSV infected rabbits. Steroid treatment alone significantly increased the antibody response to HSV, but this effect was not enhanced by vitamin A. The slight beneficial effect on HSV keratitis could be attributed to the known effect of vitamin A on promoting epithelial healing rather than an enhancement of immunity. For this purpose, local application of vitamin A may be just as effective and much less toxic than administration for systemic effect. PMID- 6258546 TI - Adenoid cystic carcinoma of the minor salivary glands: long-term survival with planned combined therapy. PMID- 6258548 TI - Malignant fibrous histiocytoma of the nose and nasopharynx. PMID- 6258547 TI - Bell's palsy and herpes simplex virus. AB - The possible association of some viral infections with the onset of Bell's palsy was examined in a study of 142 patients. The number of probable recent viral infections, as judged by increase in antibody titers or presence of IgM antibodies, did not differ statistically from that found in a sex- and age matched control group. However, a higher prevalence of herpes simplex virus (HSV) antibodies was found in the patient group with both a complement-fixation (CF) test and a radioimmunoassay (RIA). Moreover, titers of HSV CF antibodies and antibodies against HSV envelope antigens (RIA) were higher in the patient group. The possibility of reactivated HSV infection and transient demyelination of the facial nerve being causatively associated with Bell's palsy is discussed. PMID- 6258550 TI - Vestibular hair cell pathology in the Shaker-2 mouse. AB - The circling-waltzing behaviour of the Shaker-2 mouse is suggested, at least in part, to be of peripheral origin. In this hereditary inner ear disease, degeneration of hair cells type I has been observed showing specific pathologic features: rod-shaped inclusion bodies and sensory hair fusion. Later, the hair cells type I are expelled into the endolymphatic space. A large number of sensory cells type II are morphologically normal. The failure of earlier investigators to demonstrate pathological changes in the sensory epithelia of this animal is likely to be due to the use of light microscopical methods only. PMID- 6258551 TI - A clinical evaluation of serum angiotensin converting enzyme in sarcoidosis. AB - Angiotensin converting enzyme was measured in the serum of 52 patients with sarcoidosis, 67 healthy control subjects and 64 patients with pulmonary and non pulmonary diseases. The patients with sarcoidosis were classified on clinical grounds as having active or inactive disease. In 26 patients with active sarcoidosis not taking corticosteroids the mean serum ACE was significantly higher than in normal controls (P less than 0 . 001). 73% of these patients had elevated serum ACE. Only two out of 12 (17%) patients with inactive sarcoidosis not taking corticosteroids had elevated serum ACE. Serum ACE was normal in patients taking oral corticosteroids for longer than two weeks. Eighty per cent of patients with active sarcoidosis with radiological evidence of pulmonary parenchymal involvement had an elevated serum ACE compared to 25% in patients with normal chest X-rays and 60% of those with bilateral hilar lymphadenopathy. All sarcoid patients with hypercalcaemia had elevated serum ACE whereas only half of those with normal serum calcium had elevated ACE. In the patients with other thoracic and granulomatous conditions serum ACE was normal or rarely marginally elevated. Serum ACE appears to be of value in the diagnosis of active sarcoidosis. PMID- 6258549 TI - [Comparative morphology of lymphoepithelial carcinoma in primary tumor, metastasis, and xenograft (author's transl)]. AB - Tissue of lymphoepithelial tumor metastasis was transplanted subcutaneously to thymus-aplastic "nude" mice. After 75 days a pea-size tumor was developing which again was transplanted to further murine passages. During the second passage the tumor was growing faster and material was taken for light and electron microscopy. The results were compared with the datas obtained from the primary nasopharyngeal carcinoma and metastasis. The tumor cells of the metastasis and of the xenograft showed all morphological criteria of a non-keratinizing squamous epithelial carcinoma of undifferentiated type. The ultrastructural criteria of the human NPC-tumor cells were all present including cytoplasmic deposits of Corona viruses and Herpes virus-like particles within the nuclei and the cytoplasm. PMID- 6258552 TI - HLA typing and ACTH stimulation in the detection of carriers for 21-hydroxylase deficiency. AB - Two methods of carrier detection were applied to the siblings of two children with congenital adrenal hyperplasia due to 21-hydroxylase (21-OH) deficiency. HLA geno-typing showed that the affected children were HLA identical. One of the siblings possessed only one of the relevant haplotypes, and was shown to be heterozygous for 21-OH deficiency by the 17 alpha hydroxyprogesterone response to ACTH stimulation. The other sibling had a maternal recombination between the DR and glyoxylase-1 (GLO) loci. The ACTH stimulation test was normal and therefore confirms recent reports suggesting that the 21-OH gene is between the HLA-A and the GLO loci. Although HLA typing of family members will identify heterozygous 21 OH deficiency in most instances, biochemical definition is still required for some cases with recombinations in the short arm of chromosome 6. PMID- 6258554 TI - [Current aspects in the etiology of viral diarrheas of swine: occurrence of infections with the epizootic viral diarrhea (EVD) virus]. PMID- 6258553 TI - [Local immunization and paraimmunization: new perspectives for veterinary practice]. PMID- 6258555 TI - Repetitive DNA sequences in methotrexate- and methasquin-sensitive and -resistant Chinese hamster cell lines. AB - DNA purified from a Chinese hamster cell line of lung fibroblast origin (DC83F) was analyzed by density gradient centrifugation and by gel electrophoresis after restriction endonuclease digestion in order to fractionate discrete repetitive fractions within the total DNA. No obvious satellite DNAs were resolved using the CsCl or Ag-Cs2SO4 density gradient conditions described herein. However, analysis of the digestion products of a battery of restriction endonucleases indicated that three of these enzymes, EcoR1, HaeIII, and XhoI, yielded discrete fragments which could be visualized with EtBr staining or identified by scintillation counting of [3H]DNA. DNAs from several highly (greater than or equal to hundredfold increased resistance) antifolate-resistant sublines of DC-3F, characterized by a large homogeneously staining region (HSR) in the chromosome complement, were examined with both techniques and compared to the parental, antifolate-sensitive cell line DNA. The density gradient profiles and electrophoretic patterns of restriction endonuclease digests were identical among all the cell lines examined and were indistinguishable from those of the parental DC-3F DNA. PMID- 6258556 TI - Chemiluminescence of lipid vesicles supplemented with cytochrome c and hydroperoxide. AB - The increase in light emission of hydroperoxide-supplemented cytochrome c observed on addition of lipid vesicles was related to the degree of unsaturation of the fatty acids of the phospholipids: dipalmitoyl phosphatidylcholine was without effect, whereas dioleoyl phosphatidylcholine and soya-bean phosphatidylcholine enhanced chemiluminescence 2- and 3-fold respectively. Effects on light-emission were similar to those on O2 uptake. The chemiluminescence of the present system was sensitive to cyanide and to the radical trap 2,5-di-t-butylquinol, indicating a catlytic activity of cytochrome c and the presence of free-radical species respectively. Lipid-vesicle enhanced chemiluminescence showed different kinetic behaviours, apparently depending on unsaturation: three phases are described for soya-bean phosphatidylcholine, whereas only one phase was present in mixtures containing dipalmitoyl and dioleoyl phospholipids. Chemiluminescence of lipid vesicles supplemented with cytochrome c and hydroperoxide showed similar kinetic patterns with H2O2 and primary (ethyl) and tertiary (t-butyl and cumene) hydroperoxides. Participation of singlet molecular oxygen, mainly on the phase III of chemiluminescence, is suggested by the increase of light-emission by 1,4-diazabicyclo[2.2.2]-octane as well as by data from spectral analysis. PMID- 6258557 TI - Hormonal stimulation of cyclic AMP accumulation and glycogen phosphorylase activity in calcium-depleted hepatocytes from euthyroid and hypothyroid rats. AB - Activation of glycogen phosphorylase by hormones was examined in hepatocytes isolated from euthyroid and hypothyroid female rats and incubated by Ca2+-free buffer containing 1 mM-EGTA. Basal glycogen phosphorylase activity was decreased in Ca2+-free buffer. However, the activation of hepatocyte glycogen phosphorylase, in the absence of extracellular Ca2+, in response to adrenaline, glucagon or phenylephrine was slightly lower, whereas that by vasopressin was abolished. The activation of glycogen phosphorylase by phenylephrine, adrenaline or isoproterenol (isoprenaline) in hepatocytes from euthyroid rats incubated in the absence of Ca2+ was not accompanied by any detectable increase in total cyclic AMP. The log-dose/response curves for activation of phosphorylase by phenylephrine or low concentrations of adrenaline were the same in hepatocytes from hypothyroid as compared wit euthyroid rats, whereas the response to isoproterenol was greater in hepatocytes from hypothyroid rats. However, the increases in total cyclic AMP accumulation caused by adrenaline or isoproterenol were greater in hepatocytes from hypothyroid rats than in hepatocytes from euthyroid rats. The increases in cyclic AMP accumulation caused by adrenaline or isoproterenol in Ca2+-depleted hepatocytes from hypothyroid rats were blocked by propranolol, a beta-adrenergic antagonist. In contrast, propranolol was only partially effective asan inhibitor of the activation of glycogen phosphorylase by phenylephrine or adrenaline in hepatocytes from hypothyroid rats and ineffective on phosphorylase activation in cells from euthyroid rats. These data indicate that the alpha-adrenergic activation of glycogen phosphorylase is not affected by the absence of extracellular Ca2+, and the extent to which total cyclic AMP was increased by adrenergic amines did not correlate with glycogen phosphorylase activation. PMID- 6258558 TI - Biochemical lesions in copper-deficient rats caused by secondary iron deficiency. Derangement of protein synthesis and impairment of energy metabolism. AB - Severe copper deficiency was induced in rats by rearing nursing dams and their offsprings on a semisynthetic diet comprising all the requisite nutrients and trace metals except copper. The copper-deprived rats exhibited growth retardation, severe anaemia, loss of caeruloplasmin, decrease of cytochrome oxidase, accumulation of salt-soluble collagen and a drastic decrease in iron in plasma and liver. Apart from these characteristic signs of deficiency, a marked inhibition of protein synthesis was found to occur both in vivo and in cell-free liver preparations. The curtailed ability to carry out endogenously coded amino acid incorporation into protein contrasted with the unimpaired poly(U)-acid directed phenylalanine polymerization. This inhibition pattern, as well as the attendant disaggregation of the liver polyribosomes, suggested that the primary biosynthetic lesion was located at the stage of peptide-chain initiation. Concurrently with this alteration there was a pronounced depletion of the hepatic ATP content, associated with a parallel depression of mitochondrial respiration and an enhancement of ATPase activity. Supplementation of the copper-deficient diet with a 2-4-fold excess of iron (relative to the standard diet) prevented growth retardation and anaemia and restored normal energy metabolism, as well as unimpaired protein-synthesizing capacity. The conclusion that these disturbances were primarily determined by the secondary iron deficiency was also borne out by the finding that similar alterations occurred in rats maintained on a copper sufficient but iron-deficient diet. On the other hand, the iron-fortified diet failed to reverse the other signs of copper deficiency, namely the loss of caeruloplasmin, the diminished rate of cytochrome oxidase and the increase of soluble collagen. The interrelations between the various biochemical lesions induced by deprivation of copper or iron are discussed and the possible role of ATP depletion in determining the derangement of protein synthesis is considered. PMID- 6258559 TI - Complex phosphorylation activity in neurosecretosomal membranes isolated from ox neurohypophyses. AB - Homogenates of neural lobes of bovine pituitary glands were fractionated on Ficoll gradients to yield neurosecretosomes (nerve endings). The neurosecretosomes were lysed in a hypo-osmotic buffer and the membranes were separated from the soluble components by centrifugation. On incubation with [gamma-32P]ATP this membrane preparation showed an endogenous phosphorylation activity, which was studied by means of gel electrophoresis in the presence of sodium dodecyl sulphate, and subsequent autoradiography. The major part of the [32P]Pi detected on the gel was shown to be incorporated into three protein bands, termed A, B and C, with minimal mol.wts. of 83 000, 59 000 and 47 000 respectively. The phosphorylation of these three proteins was studied under a variety of experimental conditions. The patterns obtained were partly similar. However, important individual differences were noted, particularly with respect to the effects of cyclic AMP, Mg2+ and Ca2+. On the basis of these differences, it is suggested that in this system the phosphorylation activity is heterogenous, bands A, B and C each reflecting the presence of a different site of phosphate turnover. The relationship of bands A, B and C to several of the previously described phosphoproteins in the brain is discussed. PMID- 6258560 TI - The nature of the link between potassium transport and phosphate transport in Escherichia coli. AB - A series of mutants of Escherichia coli, combining defects in either of the two phosphate transport systems with defects in one or more of the potassium transport systems, was used to study the nature of the previously observed obligatory requirement for each one of these ions in the transport of the other. The results show that no pair of systems is obligatorily linked, and that either ion can be transported by any one of its systems, provided that a means of entry for the other ion is available. Furthermore, in the total absence of Pi, K+ entry accompanies the transport of other anions, such as aspartate, glutamate, sn glycero-3-phosphate and glucose 6-phosphate. The results indicate that Pi and the other anions enter by symport with protons, and that a simultaneous K+/H+ exchange, which would serve to maintain the intracellular pH, is responsible for the observed K+ 'symport' with these anions. PMID- 6258561 TI - Action of calcium ions on spinach (Spinacia oleracea) chloroplast fructose bisphosphatase and other enzymes of the Calvin cycle. AB - Thiol-treated spinach (Spinacia oleracea) chloroplast fructose bisphosphatase is powerfully inhibited by Ca2+ non-competitively with respect to its substrate, fructose 1,6-bisphosphate. 500 microM-Ca2+ causes virtually complete inhibition and the Ki is 40 microM. Severe inhibition of sedoheptulose bisphosphatase is also caused by Ca2+. A role for Ca2+ in regulation of the Calvin cycle in spinach chloroplasts is proposed. PMID- 6258562 TI - Deterioration of rat liver mitochondria under conditions of metabolite deprivation. AB - In a previous study [Parce, Cunningham & Waite (1978) Biochemistry 17, 1634-1639] changes in mitochondrial phospholipid metabolism and energy-linked functions were monitored as coupled mitochondria were aged in iso-osmotic sucrose solution at 18 degrees C. The sequence of events that occur in mitochondrial deterioration under the above conditions have been established more completely. Total adenine nucleotides are depleted early in the aging process, and their loss parallels the decline in respiratory control. Related to the loss of total adenine nucleotides is a dramatic decrease in ADP and ATP translocation (uptake). The decline of respiratory control is due primarily to a decrease in State-3 respiration; loss of this respiratory activity can be related to the decline in ADP translocation. Mitochondrial ATPase activity does not increase significantly until State-4 respiration has increased appreciably. At the time of loss of respiratory control the ATPase activity increases to equal the uncoupler-stimulated activity. The H+/O ratio and P/O ratios do not decrease appreciably until respiratory control is lost. Similarly, permeability of the membrane to the passive diffusion of protons increases only after respiratory control is lost. There observations reinforce our earlier conclusion that there are two main phases in mitochondrial aging. The first phase is characterized by loss of the ability to translocate adenine nucleotides. The second phase is characterized by a decline in the ability of the mitochondrion to conserve energy (i.e. maintain a respiration driven proton gradient) and to synthesize ATP. PMID- 6258563 TI - The rate of ATP synthesis by submitochondrial particles can be independent of the magnitude of the protonmotive force. AB - The problem of whether the rate of ATP synthesis is proportional to the magnitude of the protonmotive force has been studied in submitochondrial particles. It was found that the rate of ATP synthesis can decrease at constant protonmotive force and is more closely related to the rate of substrate oxidation. PMID- 6258564 TI - Inhibition of adenosine triphosphatase, 5-hydroxytryptamine transport and proton translocation activities of resealed chromaffin-granule 'ghosts'. AB - 1. Highly purified resealed chromaffin-granule ;ghosts' were assayed for ATPase and ATP-driven H(+)-translocation and 5-hydroxytryptamine-uptake activities, and for 5-hydroxytryptamine uptake driven by an imposed transmembrane H(+)-gradient. The effects of several inhibitors on these activities were studied. 2. Dicyclohexylcarbodi-imide inhibits all of these activities, but not in parallel; at low concentrations it decreases the permeability of the membrane to protons. 3. 4-Chloro-7-nitrobenzofuran (Nbf-Cl) and silicotungstate inhibit ATP-dependent activities, without effect on 5-hydroxytryptamine uptake driven by an imposed H(+)-gradient. 4. Tributyltin chloride inhibits all of the activities. 5. Treatment of the ;ghosts' with low concentrations of urea inhibits 5 hydroxytryptamine uptake and ATP-dependent generation of a transmembrane H(+) gradient, without inhibiting ATPase activity. 6. Nbf-Cl and silicotungstate are without effect on the rate of leakage of 5-hydroxytryptamine from preloaded ;ghosts', whereas dicyclohexylcarbodi-imide and tributyltin chloride accelerate the rate of leakage. 7. Treatment of the membranes with (14)C-labelled Nbf-Cl labels several proteins; membranes treated with dicyclohexyl[(14)C]carbodi-imide are labelled predominantly in a protein of low molecular weight, which may be analogous to the mitochondrial H(+)-conducting proteolipid. 8. It is concluded that Nbf-Cl and silicotungstate inhibit the H(+)-translocating ATPase of the granule membrane; that dicyclohexylcarbodi-imide inhibits the ATPase, and inhibits 5-hydroxytryptamine accumulation by accelerating leakage of the amine; and that the effects of tributyltin chloride are due to inhibition of the ATPase, and collapse of the transmembrane H(+)-gradient through OH(-)-anion exchange. PMID- 6258565 TI - Effect of compound D-600 (methoxyverapamil) on gluconeogenesis and on acceleration of the process by alpha-adrenergic stimuli in rat kidney tubules. AB - 1. Tubule fragments were isolated from renal cortex of fed rats and glucose formation was measured after incubation with 5 mM-sodium lactate. 20 Compound D 600 (10-100 microM) decreased gluconeogenesis from lactate. This inhibition of the process by compound D-600 increased with increasing extracellular Ca2+ concentration, was overridden by noradrenaline and diminished by starvation for 24 h. 3. Inhibition of lactate-supported gluconeogenesis by compound D-600 was not prevented by the alpha 1-adrenoceptor antagonist thymoxamine. 4. Compound D 600 had little effect on gluconeogenesis from 2-oxoglutarate and increased gluconeogenesis from succinate. 5. Compound D-600 opposed stimulation of gluconeogenesis by noradrenaline or oxymetazoline (a selective alpha-adrenoceptor agonist) in a manner suggesting that compound D-600 is an alpha-adrenoceptor blocker. Oxymetazoline was more sensitive than noradrenaline to blockade by both compound D-600 and by the conventional alpha-adrenoceptor antagonist phentolamine. Noradrenaline became more sensitive to blockade by compound D-600 when extracellular Ca2+ was decreased. 6. Compound D-600 did not block stimulation of gluconeogenesis by angiotensin or cyclic AMP. PMID- 6258566 TI - The orientation of iron-sulphur clusters in membrane multilayers prepared from aerobically-grown Escherichia coli K12 and a cytochrome-deficient mutant. AB - 1. Membrane particles prepared from ultrasonically-disrupted, aerobically-grown Escherichia coli were centrifuged on to a plastic film that was supported perpendicular to the centrifugal field to yield oriented membrane multilayers. In such preparations, there is a high degree of orientation of the planes of the membranes such that they lie parallel to each other and to the supporting film. 2. When dithionite- or succinate-reduced multilayers are rotated in the magnetic field of an e.p.r. spectrometer, about an axis lying in the membrane plane, angular-dependent signals from an iron-sulphur cluster at g(x)=1.92, g(y)=1.93 and g(z)=2.02 are seen. The g=1.93 signal has maximal amplitude when the plane of the multilayer is perpendicular to the magnetic field. Conversely, the g=2.02 signal is maximal when the plane of the multilayer is parallel with the magnetic field. 3. Computer simulations of the experimental data show that the cluster lies in the cytoplasmic membrane with the g(y) axis perpendicular to the membrane plane and with the g(x) and g(z) axes lying in the membrane plane. 4. In partially-oxidized multilayers, a signal resembling the mitochondrial high potential iron-sulphur protein (Hipip) is seen whose g(z)=2.02 axis may be deduced as lying perpendicular to the membrane plane. 5. Appropriate choice of sample temperature and receiver gain reveals two further signals in partially reduced multilayers: a g=2.09 signal arises from a cluster with its g(z) axis in the membrane plane, whereas a g=2.04 signal is from a cluster with the g(z) axis lying along the membrane normal. 6. Membrane particles from a glucose-grown, haem deficient mutant contain dramatically-lowered levels of cytochromes and exhibit, in addition to the iron-sulphur clusters seen in the parental strain, a major signal at g=1.90. 7. Only the latter may be demonstrated to be oriented in multilayer preparations from the mutant. 8. Comparisons are drawn between the orientations of the iron-sulphur proteins in the cytoplasmic membrane of E. coli and those in mitochondrial membranes. The effects of diminished cytochrome content on the properties of the iron-sulphur proteins are discussed. PMID- 6258567 TI - Metabolism of adenine nucleotides by ectoenzymes of vascular endothelial and smooth-muscle cells in culture. AB - 1. Pig aortic endothelial and smooth-muscle cells in culture rapidly catabolize exogenous ATP, ADP or AMP. 2. In both cell types catabolism is due to Mg2+ stimulated ectoenzymes. 3. Inhibition and substrate-specificity studies suggest that both cell types possess three distinct ectonucleotidases, namely nucleoside triphosphatase (EC 3.6.1.15), nucleoside diphosphatase (EC 3.6.1.6) and 5' nucleotidase (EC 3.1.3.5), as well as nucleoside diphosphate kinase (EC 2.7.4.6). 4. These ectonucleotidase systems could be of importance in the regulation of neurotransmission, blood platelet function and vasodilation. PMID- 6258568 TI - Restoration of guanine nucleotide- and fluoride-stimulated activity to an adenylate cyclase-deficient cell line with affinity-purified guanine nucleotide regulatory protein. AB - A guanine nucleotide-binding protein purified from turkey erythrocytes by affinity chromatography confers both F-- and guanine nucleotide-stimulation of adenylate cyclase to membranes from CYC- cells, a mutant cell line deficient in these responses. Interaction of turkey erythrocyte membranes with beta-adrenergic agonists before affinity chromatography, which is essential for binding of the guanine nucleotide regulatory protein to the affinity matrix, was also required for recovery of F--stimulation restoring activity in the affinity eluate. PMID- 6258569 TI - Phosphate utilization and constitutive synthesis of phosphatases in Thermoactinomyces vulgaris Tsilinsky. AB - Thermoactinomyces vulgaris utilized both organic and inorganic phosphates with equal efficiency for its growth. The specific activities of the thermophilic acid and alkaline phosphatases were found to be maximum at 1 mM concentration of each phosphate source. All the phosphatase isoenzymes (three alkaline and one acidic) were observed irrespective of the substrate source and concentration, suggesting constitutive synthesis of the enzymes. During growth and differentiation, both acid and alkaline phosphatases exhibited uniformly stable patterns of isoenzymes with slight variations in their specific activities. PMID- 6258570 TI - The interaction between methanol dehydrogenase and the autoreducible cytochromes c of the facultative methylotroph Pseudomonas AM1. AB - Cytochromes cH and cL were autoreduced at high pH (pK greater than 10) and the autoreduced cytochromes reacted with CO. The autoreduction was first-order with respect to oxidized cytochrome c and was reversible by lowering the pH. Pure methanol dehydrogenase reduced cytochrome c (in the absence of methanol) by lowering the pK for autoreduction to less than 8.5. A mechanism is proposed for the autoreduction of cytochrome c and its involvement in the reaction with methanol dehydrogenase. PMID- 6258572 TI - Tumour calcitonin. Interaction with specific calcitonin receptors. AB - The human epidermoid bronchial carcinoma (BEN) cell line has been shown to have specific membrane binding sites for calcitonin and to secrete high-molecular weight forms (ranging from 40000 to 10000) of immunoreactive calcitonin. Synthetic salmon and human calcitonins and a thyroid extract of porcine calcitonin have been shown to displace 125I-labelled salmon calcitonin from the receptors in a dose-related fashion. The binding to these receptors of calcitonins derived from the BEN cell line and a medullary thyroid carcinoma with molecular weights ranging from 28000 to 3500 (both separated by gel-filtration chromatography) has been investigated. Neither major peaks of BEN-cell-line calcitonin showed receptor binding activity. Only one form of medullary thyroid carcinoma calcitonin, that which co-eluted with synthetic calcitonin monomer on gel-filtration chromatography, caused any significant displacement of labelled hormone from the receptors. PMID- 6258571 TI - A high-affinity cytosol binding protein for 1 alpha,25-dihydroxycholecalciferol in the uterus of Japanese quail. AB - Cytosol fractions prepared from the uterine mucosa of egg-laying Japanese Quail were analysed for binding of the metabolites of cholecalciferol. When the uterus was incubated at 37 degrees C with various radioactive metabolites of cholecalciferol, the nuclear fraction incorporated only 1 alpha,25 dihydroxy[3H]cholecalciferol. When the uterus was incubated at 0 degree C with 1 alpha,25-dihydroxy[3H]cholecalciferol, most of the radioactivity was found in the cytosol. Translocation of 1 alpha,25-dihydroxy[3H]cholecalciferol from the cytosol to the nucleus was temperature-dependent. The addition of 100-fold excess amounts of unlabelled 1 alpha-25-dihydroxycholecalciferol significantly diminished the nuclear binding of 1 alpha,25-dihydroxy[3H]cholecalciferol. The cytosol fraction contained a 3.5 S macromolecule that specifically binds 1 alpha,25-dihydroxy[3H]cholecalciferol. The dissociation constant was 0.39 nM and the maximal binding was 55 fmol/mg of protein. These results strongly suggest that the uterus in egg-laying birds is a target organ or 1 alpha,25 dihydroxycholecalciferol. PMID- 6258575 TI - The inactivation of rat adipocyte Mg2+-dependent phosphatidate phosphohydrolase by noradrenaline. AB - The inactivation of rat adipocyte Mg2+-dependent phosphatidate phosphohydrolase by noradrenaline [Cheng & Saggerson (1978) FEBS Lett. 87, 65--68; Cheng & Saggerson (1978) FEBS Lett. 93, 120--124] persists for at least 40 min in crude defatted homogenates kept at 0 degrees C or 20 degrees C, but is diminished at 37 degrees C. The effect of noradrenaline persists through the isolation of post 105000 g supernatants and is then stable in these preparations at 0 degrees C and 37 degrees C. Inclusion of albumin (10--20 mg/ml) in homogenization buffers abolishes the effect of noradrenaline. The effect of noradrenaline is not removed by dialysis of extracts or by raising the concentrations of Mg2+ or phosphatidate in assays. PMID- 6258573 TI - Components involved in virally mediated membrane fusion and permeability changes. AB - 1. Intact F glycoprotein is required to induce permeability changes in Lettree cells or in erythrocytes. Some HN glycoproteins may also be required. Permeability changes thus offer a simple, accurate and rapid means of assaying the integrity of F glycoprotein in certain viral preparations. 2. The '1-day' virus (which contains intact F glycoprotein but which differs morphologically from '3 day' virus) does not cause permeability changes; it can be rendered active by various physical treatments. It is concluded that the environment in which F glycoprotein is embedded is a determining factor for permeability changes. 3. The entry of fluorescently labelled peptides into cells made permeable by virus has been measured. Peptides having a molecular weight in excess of 1000 enter poorly, suggesting a 'pore' size of approx. 1 nm in diameter. 4. Two novel assay methods concerned with virus--cell fusion are described. The first measures the fluorescence enhancement that occurs when anthroylstearate is transferred from anthroylstearate-labelled virus to cells. The second measures the giant-cell formation that occurs when partially fused erythrocytes are exposed to hypo-osmotic treatment. The '1-day' virus is active in these assays. In contrast with permeability changes, virus--cell fusion is insensitive to changes in external Ca2+-concentration. 5. The results are compatible with a model [Knutton & Pasternak (1979) Trends Biochem. Sci. 4, 220- 223; Impraim, Foster, Micklem & Pasternak (1980) Biochem. J. 186, 847--860] in which virus--cell fusion is a prerequisite for permeability changes, and in which permeability changes are the cause of haemolysis and giant-cell (polykaryon) formation. PMID- 6258574 TI - Survey of virally mediated permeability changes. AB - 1. Sendai virus causes permeability changes when added to freshly isolated brain cells (cerebellum or ependymal cells) or to a culture of forebrain cells. 2. Sendai virus causes permeability changes when added to organ cultures of ferret lung or nasal turbinate. Influenza virus causes no permeability changes under these conditions. 3. Rabies virus and vesicular-stomatitis virus, in contrast with Sendai virus, do not cause permeability changes in BHK cells or Lettree cells. 4. Serum from patients suffering from viral hepatitis does not cause permeability changes in human leucocytes; addition to Sendai virus causes permeability changes. 5. It is concluded that permeability changes accompanying viral entry occur only with certain types of paramyxovirus, but that there is little restriction on cell type. 6. MDBK cells infected with Sendai virus show permeability changes during viral release, similar to those that occur during viral entry. Because these changes do not appear to be restricted to paramyxoviruses, they may have considerable clinical significance. PMID- 6258576 TI - Asymmetric distribution of cytochrome P-450 and NADPH--cytochrome P-450 (cytochrome c) reductase in vesicles from smooth endoplasmic reticulum of rat liver. AB - 1. The topography of cytochrome P-450 in vesicles from smooth endoplasmic reticulum of rat liver has been examined. Approx. 50% of the cytochrome is directly accessible to the action of trypsin in intact vesicles whereas the remainder is inaccessible and partitioned between luminal-facing or phospholipid embedded loci. Analysis by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis reveals three major species of the cytochrome. Of these, the variant with a mol.wt. of 52000 is induced by phenobarbitone and this species is susceptible to trypsin. 2. After trypsin treatment of smooth membrane, some NADPH cytochrome P-450 (cytochrome c) reductase activity remains and this remaining activity is enhanced by treatment with 0.05% deoxycholate, which renders the membranes permeable to macromolecules. In non-trypsin-treated control membranes the reductase activity is increased to a similar extent. These observations suggest an asymmetric distribution of NADPH-cytochrome P-450 (cytochrome c) reductase in the membrane. 3. As compared with dithionite, NADPH reduces only 44% of the cytochrome P-450 present in intact membranes. After tryptic digestion, none of the remaining cytochrome P-450 is reducible by NADPH. 4. In the presence of both a superoxide-generating system (xanthine plus xanthine oxidase) and NADPH, all the cytochrome P-450 in intact membrane (as judged by dithionite reducibility) is reduced. The cytochrome P-450 remaining after trypsin treatment of smooth vesicles cannot be reduced by this method. 5. The superoxide-dependent reduction of cytochrome P-450 is prevented by treatment of the membranes with mersalyl, which inhibits NADPH-cytochrome P-450 (cytochrome c) reductase. Thus the effect of superoxide may involve NADPH-cytochrome P-450 reductase and cytosolically orientated membrane factor(s). PMID- 6258577 TI - Cellular uptake of retinoic acid in vitro. AB - Incubation of chick embryo skin and mouse colon tumour 26 with [3H]retinoic acid resulted in the formation of a complex of retinoic acid and its cellular binding protein both in cytosol and in nuclei. Formation of the ligand--protein complex was temperature-dependent and increased with increases in retinoic acid concentration in the incubation medium. About 3--8% of the ligand present in the cytosol was associated with the nuclei. PMID- 6258578 TI - Structural studies on heparan sulphate from human lung fibroblasts. Characterization of oligosaccharides obtained by selective periodate oxidation of D-glucuronic acid residues followed by scission in alkali. AB - 1. (3)H- and (35)S-labelled heparan sulphate was isolated from monolayers of human lung fibroblasts and subjected to degradations by (a) deaminative cleavage and (b) periodate oxidation/alkaline elimination. Fragments were resolved by gel- and ion-exchange-chromatography. 2. Deaminative cleavage of the radioactive glycan afforded mainly disaccharides with a low content of ester-sulphate and free sulphate, indicating that a large part (approx. 80%) of the repeating units consisted of uronosyl-glucosamine-N-sulphate. Blocks of non-sulphated [glucuronosyl-N-acetyl glucosamine] repeats (3-4 consecutive units) accounted for the remainder of the chains. 3. By selective oxidation of glucuronic acid residues associated with N-acetylglucosamine, followed by scission in alkali, the radioactive glycan was degraded into a series of fragments. The glucuronosyl-N acetylglucosamine-containing block regions yielded a compound N-acetylglucosamine R, where R is the remnant of an oxidized and degraded glucuronic acid. Periodate insensitive uronic acid residues were recovered in saccharides of the general structure glucosamine-(uronic acid-glucosamine)(n)-R. 4. Further degradations of these saccharides via deaminative cleavage and re-oxidations with periodate revealed that iduronic acid may be located in sequences such as glucosamine-N sulphate-->iduronic acid-->N-acetylglucosamine. Occasionally the iduronic acid was sulphated. Blocks of iduronic acid-containing repeats may contain up to five consecutive units. Alternating arrangements of iduronic acid- and glucuronic acid containing repeats were also observed. 5. (3)H- and (35)S-labelled heparan sulphates from sequential extracts of fibroblasts (medium, EDTA, trypsin digest, dithiothreitol extract, cell-soluble and cell-insoluble material) afforded similar profiles after both periodate oxidation/alkaline elimination and deaminative cleavage. PMID- 6258579 TI - Partial purification and characterization of human erythrocyte phosphoglycollate phosphatase. AB - Human erythrocytes contain a phosphatase that is highly specific for phosphoglycollate. It shows optimum pH of 6.7 and has Km 1 mM for phosphoglycollate. The molecular weight appears to be about 72000. The enzyme is a dimeric molecule having subunits of mol. wt. about 35000. It could be purified approx. 4000-fold up to a specific activity of 5.98 units/mg of protein. The activity of the enzyme is Mg2+-dependent. Co2+, and to a smaller extent Mn2+, may substitute for Mg2+. Half-maximum inhibition of the phosphatase by 5,5'-dithiobis (2-nitrobenzoate), EDTA and NaF is obtained at 0.5 microM, 1 mM and 4 mM respectively. Moreover, it needs a univalent cation for optimum activity. Phosphoglycollate phosphatase is a cytoplasmic enzyme. Approx. 5% of its total activity is membrane-associated. This part of activity can be approx. 70% solubilized by freezing, thawing and treatment with 0.25% Triton X-100. PMID- 6258580 TI - Interaction of pseudomonic acid A with Escherichia coli B isoleucyl-tRNA synthetase. AB - Sodium pseudomonate was shown to be a powerful competitive inhibitor of Escherichia coli B isoleucyl-tRNA synthetase (Ile-tRNA synthetase). The antibiotic competitively inhibits (Ki 6 nM; cf. Km 6.3 microM), with respect top isoleucine, the formation of the enzyme . Ile approximately AMP complex as measured by the pyrophosphate-exchange reaction, and has no effect on the transfer of [14C]isoleucine from the enzyme . [14C]Ile approximately AMP complex to tRNAIle. The inhibitory constant for the pyrophosphate-exchange reaction was of the same order as that determined for the inhibition of the overall aminoacylation reaction (Ki 2.5 nM; cf. Km 11.1 microM). Sodium [9' 3H]pseudomonate forms a stable complex with Ile-tRNA synthetase. Gel-filtration and gel-electrophoresis studies showed that the antibiotic is only fully released from the complex by 5 M-urea treatment or boiling in 0.1% sodium dodecyl sulphate. The molar binding ratio of sodium [9'-3H]pseudomonate to Ile-tRNA synthetase was found to be 0.85:1 by equilibrium dialysis. Aminoacylation of yeast tRNAIle by rat liver Ile-tRNA synthetase was also competitively inhibited with respect to isoleucine, Ki 20 microM (cf. Km 5.4 microM). The Km values for the rat liver and E. coli B enzymes were of the same order, but the Ki for the rat liver enzyme was 8000 times the Ki for the E. coli B enzyme. This presumably explains the low toxicity of the antibiotic in mammals. PMID- 6258581 TI - A reliable radiochromatographic assay technique for hepatic microsomal 16 alpha hydroxylase activity towards oestrone 3-sulphate. Comparison between pigmented and non-pigmented mature guinea pigs. AB - A reliable procedure for the assay of liver microsomal 16 alpha-hydroxylation of oestrone 3-sulphate has been developed for the guinea pig. It is based on the rapid, quantitative separation of oestradiol and oestriol by Sephadex LH-20 columns after the chemical reduction and enzymic hydrolysis of the incubation products. Microsomal preparations and incubation conditions that optimized 16 alpha-hydroxylation of oestrone 3-sulphate were employed. Under these circumstances, reduction of the substrate at C-17 and hydrolysis of the sulphate were minimized. Conditions were established that yielded reaction linearity with respect to time and microsomal concentration. This hydroxylation had an absolute requirement for NADPH, which could not be satisfied by NADH. Apparent Km values for oestrone 3-sulphate and NADPH, under the conditions used, were 14 microM and 0.17 mM respectively. 16 alpha-Hydroxylase activity was present in the liver microsomal fraction from heavily pigmented, female English Shorthaired guinea pigs. Much lower activity was detected in mature pigmented males and albino females. No activity could be demonstrated in mature, albino males. PMID- 6258582 TI - Purification and partial characterization of high-molecular-weight forms of ectopic calcitonin from a human bronchial carcinoma cell line. AB - Studies on the high-molecular-weight immunoreactive calcitonin produced ectopically in culture by an epidermoid bronchial carcinoma cell line are reported. In cell-exposed medium, the principal component has a molecular weight of 40000 and molecules of mol.wts. 13000 and 10000 also occur. Only a trace amount of material co-eluting with 35000-mol.wt. human calcitonin is detectable. None of the calcitonins show cross-reactivity with anti-corticotropin serum. The 40000-mol.wt. immunoreactive calcitonin is readily proteolysed to the 13000- and 10000-mol.wt. components, but the 10000-mol.wt. component behaves as a comparatively stable 'core' molecule. By using immunoprecipitation and high pressure liquid chromatography (h.p.l.c.), it is possible to prepare radiochemically homogeneous 10000-mol.wt. immunoreactive calcitonin from cells grown in the presence of individual 35S- or 3H-labelled amino acids. Peptide mapping of enzymic digests of this material by h.p.l.c. shows that it contains peptides in common with synthetic human calcitonin. PMID- 6258583 TI - The nature of the sulphur atom liberated from xanthine oxidase by cyanide. Evidence from e.p.r. spectroscopy after 35S substitution. AB - Active xanthine oxidase was labelled specifically with 33S in the cyanide-labile site of the molybdenum centre. The Very Rapid molybdenum (V) e.p.r. signal, generated from this, shows strong coupling of 33S to molybdenum, providing unambiguous evidence that, at least in the signal-giving species, this sulphur atom is a ligand of molybdenum. The structure of the signal-giving species is discussed. PMID- 6258584 TI - The nature of the phosphate inhibitor complex of sulphite oxidase from electron paramagnetic-resonance studies using oxygen-17. AB - Studies of the effect of substitution with 17O on the e.p.r. spectra at 9 and 35 GHz of Mo(V) in the phosphate complex of sulphite oxidase are reported. Substitution of 17O-enriched water for normal water, for samples of the enzymes reduced by sulphite in the presence of normal phosphate, produced no detectable effect on the e.p.r. signal. If phosphate substituted with 17O was used, coupling due to 17O, producing large anisotropic splittings in the spectrum, was clearly detectable. It is concluded that phosphate is co-ordinated directly to molybdenum in the active site of the enzyme, in an equatorial type of ligand position. An oxygen ligand must be displaced from the molybdenum in the process of binding the phosphate. Implications concerning the mechanism of the enzyme reactions are discussed. PMID- 6258585 TI - Ecto-enzymes of mammary gland and its tumours. Ca2+- or Mg2+-stimulated adenosine triphosphatase and its perturbation by concanavalin A. AB - Intact viable 13762 mammary-adenocarcinoma ascites cells hydrolyse added ATP. The localization of hydrolysis product and inactivation by the slowly penetrating chemical reagent diazotized sulphanilic acid indicate that this ATPase is at the external surface of the cell. A number of features differentiate this enzyme from mitochondrial, myosin and cation-transport ATPases. It is stimulated by either Ca2+ or Mg2+ and has little or no activity in their absence. It is insensitive to ouabain, oligomycin and azide. It is the major ATPase activity found in homogenates of gently disrupted 13762 cels. The ATPase activity is inhibited at high substrate concentrations and shows an apparent stimulation by concanavalin A in isolated membranes, but not in intact cells. The stimulation by concanavalin A results predominantly from a release from substrate inhibition. PMID- 6258587 TI - Protein kinase and cyclic AMP levels in differentiating myoblasts are altered by extracellular calcium. PMID- 6258586 TI - Spectrophotometric assay, solubilization and purification of brain 2':3'-cyclic nucleotide 3'-phosphodiesterase. AB - 1. A spectrophotometric assay of 2':3'-cyclic nucleotide 3'-phosphodiesterase (EC 3.1.4.37) based on the use of an acid-base indicator and a buffer having identical pKa values is described. The assay is simple and rapid; it was particularly convenient for monitoring the enzyme activity at various stages of purification. 2. Several proteinases were examined for their ability to solubilize 2':3'-cyclic nucleotide 3'-phosphodiesterase from delipidated brain white matter. Trypsin (EC 3.4.21.4) and elastase (EC 3.4.21.11) appeared to be more effective than the other proteinases examined. Trypsin, however, caused inactivation; elastase was therefore chosen to solubilize 2':3'-cyclic nucleotide 3'-phosphodiesterase. When a partially purified preparation of 2':3'-cyclic nucleotide 3'-phosphodiesterase was treated with elastase, 2':3'-cyclic nucleotide 3'-phosphodiesterase was solubilized nearly quantitatively. Elastatinal, a specific inhibitor of elastase, specifically inhibited the solubilization with elastase. 3. 2':3'-cyclic nucleotide 3'-phosphodiesterase was purified from bovine brain white matter by: (i) delipidation; (ii) solubilization with hexadecyltrimethylammonium bromide; (iii) gel chromatography on Sepharose; (iv) ethanol precipitation and resolubilization by digestion with elastase; (v) chromatography on DEAE-Sephadex; (vi) affinity chromatography on 8-(6 aminohexyl)amino-2'-AMP-Sepharose. 4. The purified enzyme migrated as a single protein band on polyacrylamide-gel electrophoresis at pH 4.3 and on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis; the estimated mol.wt. in the latter electrophoresis was 27000-31000. Gel filtration of the purified enzyme through Sephadex G-150 indicated a mol.wt. of 31000. Therefore the purified enzyme is a monomer protein with a mol.wt. of approx. 30000. PMID- 6258588 TI - Effect of polymyxins on glycogen phosphorylase. PMID- 6258589 TI - Isolation of glutathione from bovine thymus and its significance to research relevant to immune systems. PMID- 6258590 TI - Isolation of thymone A from bovine thymus partial chemical and biological characterization. PMID- 6258591 TI - Isolation, partial chemical and biological characterization of thymone B. PMID- 6258592 TI - The effect of reverse transformation agents on alpha-aminoisobutyric acid uptake in transformed and non-transformed cells. PMID- 6258593 TI - An Rts1-derivative plasmid conferring UV sensitivity on Escherichia coli host. PMID- 6258595 TI - Activation of cyclic AMP-dependent protein kinases I and II by cyclic 3',5' phosphates of 9-beta-d-ribofuranosylpurine and 2-beta-D ribofuranosylbenzimidazole. PMID- 6258594 TI - Stimulation of monovalent ion fluxes and DNA synthesis in 3T3 cells by melittin and vasopressin is not mediated by phospholipid deacylation. PMID- 6258596 TI - Demonstration and characterization of partial glyceride specific lipases in pig thyroid plasma membranes. PMID- 6258597 TI - Synthesis and biological activities of pseudopeptide analogues of LH-RH: agonists and antagonists. PMID- 6258598 TI - Inhibition of mouse brain synaptosomal gamma-aminobutyric acid transport by pyridoxal 5'-phosphate. PMID- 6258600 TI - Type-specific collagenolysis: a type V collagen-degrading enzyme from macrophages. PMID- 6258599 TI - Control of growth by intracellular potassium and sodium concentrations is relaxed in transformed 3T3 cells. PMID- 6258601 TI - Accumulation of epidermal growth factor within cells does not depend on receptor recycling. PMID- 6258602 TI - Energized cation transport by complex III (ubiquinone-cytochrome C reductase). PMID- 6258603 TI - Retinoid inhibition of superoxide anion radical production by human polymorphonuclear leukocytes stimulated with tumor promoters. PMID- 6258604 TI - Thyroid dependent maturation of beta-adrenergic receptors in the rat lung. PMID- 6258605 TI - Teleocidin B inhibits binding of epidermal growth factor to cellular receptors probably by the same mechanism as phorbol esters. PMID- 6258607 TI - Proteolysis of rat liver plasma membranes cancels the guanine nucleotide sensitivity of agonist binding to the alpha-adrenoceptor. PMID- 6258606 TI - beta-Endorphin- (1-27): acetylation of alpha-amino groups enhances immunoreactivity but diminishes analgesic and receptor-binding activities with no changes in circular dichroism spectra. PMID- 6258608 TI - [Dietetic considerations of the peptic ulcer treatment (author's transl)]. AB - Stated that the alimentary inconguities, the improper mastication and the quickly eaten of foods are to avoid for the direct irritant effect on the stomach, the authors have examinate the various dietetic treatments, imploied for peptic ulcer and they conclude that only during the acute clinical phase more restrictive regimens are necessary. When the patient in on way of recovery, the alimentation must be free in agreement to the tolerance and personal taste using more variety of food. Moreover it's necessary to remember that the patient is not an "ulcer", but "his ulcer" be treated with the psycho-pathological implication correlated. PMID- 6258609 TI - [Infectious agents in the G.I. tract diseases (author's transl)]. AB - The distribution of normal intestinal flora changes in the different gut segments and is influenced by gastric pH, peristalsis, bactericidal activity of Immunoglobulins A (locally produced). Saprophytic bacteria prevent the growth of pathogenous microorganisms, partake in the production of vitamins (K, B group), can be responsible for the production of carcinogens and co-carcinogens by acting on bile-acids, food or drugs ingested, can affect the morphology of the intestinal mucosa. Enteroviruses are transient intestinal microorganisms, responsible for infectious disease whose highest incidence is summer and autumn, whose frequency is particularly elevated in malnourished subjects. PMID- 6258610 TI - [Non-A, non-B post-transfusion hepatitis. Serological survey of 85 patients with acute hepatitis following blood transfusion]. AB - In a serological survey of 85 adult patients hospitalized for an episode of transfusion-associated hepatitis, 45 were reactive for hepatitis B surface antigen and therefore diagnosed as having hepatitis B. Forty HBsAg non reactive patients were examined for development of antibody to hepatitis A and B antigens, cytomegalovirus and Epstein-Barr virus. Three patients showed serologic evidence of hepatitis B and one for hepatitis A. None of the remaining 36 subjects developed serologic evidence of acute infection with the viruses tested during the study period, so that they were classified as having so-called NANB hepatitis. As reported in other studies, analysis of the incubation period showed that two subgroups of NANB hepatitis may be identified with short and long incubation period, so that it appears likely that at least two agents are implicated in NANB hepatitis. Our data confirm that also in our area a large proportion of transfusion-associated hepatitis is related to NANB agent(s) requiring additional measures for its prevention. PMID- 6258611 TI - [Viral hepatitis type A. Seroepidemiological study in Padova and its district]. AB - In order to ascertain the real frequency of HAV infection in North-East of Italy a seroepidemiologic survey was carried out on the population of Padova and its district. The serum samples obtained from 1812 subjects (approximately the 2% of registered people) subdivided according to sex and age (5 to 5 year groups), were tested for anti-HA by radioimmunoassay. The mean prevalence of anti-HA was 69.2%. Positive subjects' frequency of 50% was reached in 15-20 year-old group, whereas more than 90% of people over 35 years of age were positive. No significant differences were observed between the sexes or between town and country populations, while the increase of the anti-HA prevalence curve was delayed in the higher socioeconomic level group. These findings testify the relevant socioeconomic and public health levels improvement in the last decades, while, on the other hand, point out the increasing risk of adulthood HAV infection. PMID- 6258612 TI - [Mycoplasmas and dysplasia of the uterine cervix]. AB - The Authors report a case-list of 395 patients vaginal specimens who were never treated with chemo-antibiotic therapy. Cell dysplastic impairments were found in 213 cases. About these dysplastic alterations, 133 are of slight type, 53 intermediate type and 27 are in advanced phase. We can say, about the last 27 cases, that the concomitance of pH greater than 6.1 in 67% of the cases and the absence of Lactobacillus acidophilus in 81.4% of the cases is not casual. Furthermore, we can notice that vaginal pH suffers an increase in dysplastic patients with a smaller colonization with Lactobacillus acidophilus that, in dysplastic advanced phase is absent in 81.4% of the cases. It is also to remark a significant increase of cases Trichomonas-positive and Mycoplasmas-positive in dysplastic patients, as compared with normal women. The results of the case-list, even if preliminary, seem to be indicative for an evolution of the studies on the relationship between uterine cervix cells and Mycoplasmas and eventual possibility the Mycoplasmas can act as carriers of oncogenic viruses such as Herpes and Papova Virus. PMID- 6258613 TI - [Erythrocyte membrane in Duchenne muscular dystrophy. II. Fluidity of lipids in dystrophic patients and their families]. AB - Electron spin resonance techniques was used to study the fluidity of intact and hemoglobin free erythrocyte membranes from patients with Duchenne muscular distrophy and from members of their family. A greater mobility of spin label motion was observed only at the surface of hemoglobin free membranes in the patients. These studies suggest alterations in lipid-protein interaction, indicating in Duchenne muscular distrophy a generalized membrane abnormality. PMID- 6258614 TI - [High and low affinity beta adrenergic receptor sites from submandibular glands of mice]. AB - Beta-adrenergic receptors from submandibular glands of mice were studied by equilibrium binding experiments. Due to the fact that some discrepancies were previously observed among different author data, we compared two methods for non specific binding substruction, that represents the major source of errors in such experiments. Data were obtained strongly suggesting the presence of multiple population of binding sites and/or negative cooperativity. PMID- 6258615 TI - [In vivo and in vitro activity of Streptococcus faecium extract on Herpes simplex virus]. AB - The effects of substance or substance extracted from Str. faecium SF 68 on HSV-1 are evaluated. The "in vivo" assay show that bacterial extract introduced i.p. in mice simultaneously with HSV-1 brought about 100% of survival, but bacterial extract after virus challenge brought about complete mortality of mice. "In vitro" assays show that bacterial extract reduce significantly PFU number. It seemed that Str. faecium extract affected the virus at the stage of adsorption on the host cells. PMID- 6258616 TI - [Effect of glucagon on blood gastrin levels in hepatic cirrhosis: correlation with blood levels of cyclic AMP]. AB - The effect of glucagon on fasting gastrin levels was studied in normal subjects and in patients with advanced liver cirrhosis. Intravenous glucagon was given e.v. at a dose of 200 ng/kg/h and produced a significant decrease of serum gastrin levels at 50 min in controls while in cirrhotic patients there was no significant decrease. (p less than 0,01) Gastrin inhibition in normal subjects during glucagon infusion was significantly correlated to a simultaneous increase found in plasma cAMP and glucose levels. These findings suggest that hypergastrinemia in cirrhosis could be consequence of the failure of glucagon metabolic interactions. PMID- 6258617 TI - [Experimental study in the effect of isoproterenol on cerebral circulation and tissue cyclic AMP concentration (author's transl)]. PMID- 6258618 TI - [Perfusion and hyperoxygenation, including a suggestion to the treatment (author's transl)]. PMID- 6258619 TI - Mechanisms of hormone action. PMID- 6258620 TI - The effect on paracetamol absorption of stimulation and blockade of beta adrenoceptors. AB - 1 The effect of drugs acting on beta-adrenoceptors on the absorption and excretion of paracetamol was studied in 26 volunteers and nine patients with mild hypertension, each subject acting as his/her own control. 2 Isoprenaline given 30 min before paracetamol significantly slowed absorption, the effect being dose related, and blocked by prior administration of propranolol. 3 When isoprenaline was given immediately before the paracetamol, absorption was not altered, although a cardiovascular response was seen. 4 Oral salbutamol also delayed paracetamol absorption. 5 Propranolol given alone increased the rate of paracetamol absorption. 6 These results with the changes in the rate of gastric emptying produced by these agents. PMID- 6258621 TI - Inhibition of the slow inward current by nifedipine in mammalian ventricular myocardium. PMID- 6258622 TI - The effect of nifedipine on the sinus and atrioventricular node of the dog heart after beta-adrenergic receptor blockade. PMID- 6258623 TI - Angiotensin-converting enzyme and its association with outcome in lung cancer. AB - Serum angiotensin-converting enzyme (SACE) in 141 patients with newly detected primary lung cincer was 22.1 +/- 6.1 nmol/ml/min (mean +/- s.d.); lower than in healthy controls (24.4 +/- 6.2 nmol/ml/min, P less than 0.02). No correlation was found between SACE and sex, age, site of cancer, histological type, or lung function. After subdivision of the patients according to increasing SACE levels: less than 16.0 (mean SACE of lung cancer--s.d.), 16.0-22.0, 22.1-28.2 and greater than 28.2 nmol/ml/min (mean SACE of lung cancer + s.d.) there was a strong association (P less than 0.001) between SACE level and the proportion of patients who were radically operated without relapse during 8-22 months follow-up. None of 23 patients within the lowest SACE range were cured, even though 7 were referred for operation after preoperative examination. In contrast, 10/25 patients (40%) within the highest SACE range were cured. The results suggest that low SACE is associated with poor prognosis in lung cancer, even in patients who are judged as being operable on preoperative evaluation; and measurement of preoperative SACE in lug cancer may be a useful prognostic indicator in this disorder. PMID- 6258624 TI - Hepatoblastoma as a cause of intrauterine fetal death. Case report. AB - A hepatoblastoma was found in a 36 week stillborn infant. The tumour compressed the inferior vena cava and was the cause of hydrops foetalis. There was also agenesis of the gall bladder. Amniotic fluid alpha-fetoprotein levels at 15 weeks were normal and did not indicate the presence of the tumour. PMID- 6258625 TI - The diet of individuals: a study of a randomly-chosen cross section of British adults in a Cambridgeshire village. AB - 1. The dietary intakes of sixty-three adults, randomly-selected from the electoral role of a large village near Cambridge, have been measured using the weighed-intake technique for 7 d. 2. Mean (+/- SD) daily intakes (g) for men and women respectively were: energy (MJ) 10.0 +/0 2.4, 8.2 +/- 2.1; fat 104 +/- 27, 90 +/- 27; protein 77 +/- 20, 67 +/- 16; carbohydrate 285 +/- 81, 229 +/- 74; sucrose 91 +/- 47, 57 +/- 33. 3. When interviewed at the end of the study 40% of subjects said they were watching their weight. 4. Women ate less food over all than men, and proportionately less potato and bread, and used only one-third as much sugar in drinks, probably in an attempt to control their weight. Men took considerably more alcohol than the women. In the age-group 20-39 years alcohol provided 9% (1.0 MJ/d) of the total energy intake in the men. 5. Wide variation in the intake of nutrients was observed amongst the individuals. For vitamin C and fibre intake this was partly partly explained by seasonal variation but for most nutrients total energy intake and food choice were the main determinants. The range of intakes of nutrients such as fat was similar in these individuals to that seen amongst countries internationally. It is suggested that if differences in nutrient intake amongst the various populations of the world can be associated with disease risk, then the same interpretation should be possible in individuals. PMID- 6258626 TI - Fibre and bowel transit times. AB - 1. Bowel transit time has been investigated in vegetarians and non-vegetarians and related to dietary fibre intake and the presence of diverticular disease. 2. Vegetarians who have less diverticular disease than non-vegetarians have more rapid transit times. 3. Subjects with total dietary fibre intake of more than 30 g/d all had transit times of less than 75 h whereas 38% of those eating less had transit times exceeding 75 h and varying up to 124 h. 4. Individuals with diverticular disease were found to have faster transit times than those without the disease. 5. The colon may respond to a fibre-depleted diet either by becoming hyperactive and prone to diverticular disease or by becoming hypoactive leading to constipation. PMID- 6258627 TI - An examination of factors which may affect the water holding capacity of dietary fibre. AB - 1. Dietary fibre has a water holding capacity (WHC) and this is a function of the fibre source and method of measurement. Water can be associated with fibre either as trapped water or bound water. This makes it difficult to predict the ability of fibre to influence stool weight in humans. 2. Examination of various fibre concentrates for chemical composition, as neutral detergent fibre (NDF), acid detergent fiber (ADF) and lignin; structure, by scanning electron microscopy; WHC, by centrifugation, suggests that WHC is more a function of fibre structure than chemical composition. Cereal fibre and vegetable fibre have a different chemical composition and are structurally very distinct. Structure is also dependent on the method of fibre preparation. 3. Measurement of WHC by centrifugation gives an estimate of the water which can be bound and also trapped by the fibre. The amount of trapped water will depend on the structure of the fibre whereas bound water will depend on the chemical composition. PMID- 6258628 TI - Interaction of netropsin and distamycin with deoxyribonucleic acid: electric dichroism study. AB - We report dichroism and equilibrium binding studies of netropsin (Net) and distamycin A3 (Dist) binding to deoxyribonucleic acid (DNA). We show that at low degrees of binding (r) to calf thymus DNA, Net induces a considerable increase in the apparent DNA length (14 A/drug molecule bound), closely analogous to the results reported earlier for Dist. In addition, we show that chicken erythrocyte DNA shows length changes similar to those of calf thymus DNA upon distamycin binding. DNA length reaches a maximum at 1 bound drug/20-30 base pairs and then decreases to its initial value by r = 0.1. This effect is not seen for two other DNAs with nearly identical A + T base pair content and may therefore arise from the details of base sequence or base modification in eukaryotic DNA. We also show that Dist binding to calf thymus DNA at low r values is positively cooperative and shows a DNA affinity which is primarily nonionic. We demonstrate that independent of the DNA to which they are bound, the Net and Dist transition moments are inclined by 43 +/- 3 degrees from the helix axis, consistent with the idea that both drugs bind inside and parallel to the DNA small groove. From dichroism measurements, we show that the conformational change induced in calf thymus DNA by Dist does not kink or bend the helix and does not substantially alter the average inclination of the bases. Finally, we outline a statistical mechanical theory for calculation of binding isotherms when binding is coupled to a DNA structural change. PMID- 6258629 TI - Structural intermediates trapped during the folding of ribonuclease A by amide proton exchange. AB - In the folding reaction of the slow-folding species (US) of ribonuclease A (RNase A), the slow isomerization of wrong proline isomers provides a suitable trap for kinetic folding intermediates at low temperatures (0--10 degrees C). Partly folded intermediates are known to accumulate before proline isomerization takes place, after which native RNase A is formed. We have been able to measure the protection from amide proton exchange which is provided by structure in the intermediates at different times along the folding pathway. Previous work has shown that, by labeling the amide protons of the unfolded protein before initiating refolding, an early folding intermediate can be detected. The new pulse-labeling method presented here can be used to label later folding intermediates. Our results indicate that, in conditions which strongly favor the native protein, intermediates are formed which provide protection against exchange. However, when folding is initiated in 2.5 M Gdn . HCl, 10 degrees C, pH 7.5, conditions in which folding goes to completion but there are no spectroscopically detectable intermediates, then no intermediates are detected by our method. Alternate minimal mechanisms for the folding of US are presented. PMID- 6258630 TI - Partial purification and characterization of a neutral protease which cleaves type IV collagen. AB - A neutral protease has been extracted from the media of cultured metastatic tumor cells and purified approximately 1000 times after sequential ammonium sulfate fractionization, concanavalin A column chromatography, and molecular sieve chromatography. The protease has an apparent molecular weight of 70 000--80 000, is inactive at acid pH, requires trypsin activation, and is inhibited by ethylene diaminetetraacetic acid but not by phenylmethanesulfonyl fluoride, N ethylmaleimide, or soybean trypsin inhibitor. The enzyme produces specific cleavage products for both chains of pro type IV collagen isolated without pepsinization and apparently cleaves at one point in a major pepsin-extracted chain of placenta type IV collagen. The partially purified enzyme fails to significantly degrade other collagens or fibronectin under digestion conditions in which specific reaction products are produced for type IV collagen. The existence of this enzyme is significant since previously described animal collagenases fail to degrade type IV collagen. Such a type IV specific collagenase could play a role in tumor invasion and may be secreted by other cells such as endothelial cells, epithelial cells, and immune cells. PMID- 6258631 TI - Nuclear magnetic resonance studies of Rhodospirillum rubrum cytochrome c'. AB - Cytochrome c' from Rhodospirillum rubrum has been studied by proton magnetic resonance (NMR) at 270 MHz. The pH and temperature-dependence properties as well as proton water relaxation enhancement and bulk susceptibility measurements were examined. We conclude that the fifth ligand to the iron is histidine. The pH dependent shift of the heme methyl resonances of the ferric protein shows pKa's at 5.8 and 8.7. The low-pH equilibrium causes only minor changes in the properties of the protein. However, the high-pH equilibrium causes large changes throughout the NMR spectra which correlate with the reported visible spectral changes. These NMR spectral changes are compared with the low-temperature EPR and Mossbauer spectroscopic data. Analyses of the NMR data show that a second histidine, which is present in the sequence of c' from R. rubrum but is not conserved in other cytochromes c', is not a "distal" histidine. The nature of the sixth ligand and the significance of the high-pH transition are discussed. PMID- 6258632 TI - Efficiency of formation of pyrimidine dimers in SV40 chromatin in vitro. AB - The efficiency of formation of pyrimidine dimers by 254-nm light was studied in mixtures of SV40 chromatin and DNA extracted from that chromatin. At high doses (beyond 380 J/m2), fewer dimers are formed in chromatin than in DNA for a given dose of radiation. This difference is about 10% as saturation with pyrimidine dimers is approached at 6840 J/m2. Conversely, at biologically repairable doses (up to 40 J/m2, less than 2 dimers/genome), significantly more dimers are produced in the chromatin than in the DNA. A maximum increase of about 50% occurs at doses producing 0.5--20 dimers/genome. With isolated nucleosomes from this chromatin, a maximum increase in dimer formation of 77% was observed. Therefore, the increased dimer formation in the whole chromatin can be wholly accounted for in the nucleosome portion. PMID- 6258633 TI - Enzymatic excision of 3-methyladenine and 7-methylguanine by a rat liver nuclear fraction. PMID- 6258634 TI - Purification and characterization of the intestinal promoter of iron(3+) transferrin formation. AB - The nonceruloplasmin enzyme located in the intestinal mucosa which promotes the incorporation of iron into transferrin has been resolved into a small, heat stable component and a heat-labile protein component. The small, heat-stable component was purified from the high-speed supernatant of intestinal mucosal homogenates by ion-exchange chromatography and gel filtration and identified as xanthine. The heat labile protein component was purified from the high-speed supernatant of intestinal mucosal homogenates by heat treatment, gel filtration, and ion-exchange chromatography. The physical, spectral, and kinetic properties of the heat-labile protein component strongly suggest that it is xanthine oxidase. By promotion of the oxidation and incorporation of iron into transferrin, intestinal xanthine oxidase could perform a similar function in iron absorption as ceruloplasmin serves in the mobilization of iron from liver stores. PMID- 6258635 TI - Isolation and properties of human neutrophil myeloperoxidase. AB - Human leukocyte myeloperoxidase has been purified to homogeneity by a three-step procedure which includes dialysis of a granule extract against low-salt buffer. Sephadex G-75 chromatography, and carboxymethylcellulose chromatography. The final product was homogeneous when examined by acid polyacrylamide gel electrophoresis and sedimentation equilibrium ultracentrifugation. The molecular weight determined by the latter procedure was 118000. With or without reduction of the protein by 2-mercaptoethanol, subunits were formed which migrated as a single band after sodium dodecyl sulfate gel electrophoresis. With reduction, the molecular weight of the apparently identical subunits was 59000, and 42000 without reduction. Other general properties of human leukocyte myeloperoxidase, including amino acid composition, amino terminal sequence analysis, and absorption spectra, are also reported. Myeloperoxidase, in the presence of hydrogen peroxide and chloride ion, and no other substrate, autoinactivates. After completion of the inactivation reaction, several oxidizable amino acids in the enzyme are modified, and the absorption peak at 430 nm disappears. The presence of a substrate of the myeloperoxidase system (alpha-1-proteinase inhibitor), or of high concentration of chloride ion, completely protects the enzyme from autoinactivation. PMID- 6258637 TI - Earthworm bioluminescence: characterization of high specific activity Diplocardia longa luciferase and the reaction it catalyzes. AB - Diplocardia longa luciferase purified by an improved procedure differs from that first described by Bellisario et al. [Bellisario, R., Spencer, T. E., & Cormier, M. J. (1972) Biochemistry 11, 2256-2266] in having much higher specific activity (40X) and firmly bound, EPR-silent copper. Improved assay conditions suggest that this protein acts as a catalyst in a bioluminescent reaction involving the degradation of 3-(isovalerylamino)-1-hydroxypropane hydroperoxide. This substrate is formed spontaneously on the addition of hydrogen peroxide to D. longa luciferin (3-(isovalerylamino)propanal). The quantum yield of the bioluminescence for this substrate is 3%. Detailed physical and chemical analyses of high specific activity D. longa luciferase indicate that it is a large (300000 daltons), asymmetric (f/fo=1.63, with 0.4 g/g hydration), multisubunit enzyme. It contains carbohydrate (6%), lipid (2%), and copper (up to 4 mol/30000 daltons). The amino acid composition is unusual with 11% by weight of the residues being either proline or hydroxyproline. PMID- 6258636 TI - Interaction of human alpha-1-proteinase inhibitor with neutrophil myeloperoxidase. PMID- 6258638 TI - Distances between structural metal ion, substrates, and allosteric modifier of fructose bisphosphatase. AB - The binding of two paramagnetic probes within a subunit of fructose bisphosphatase, viz., Mn2+ at a structural site and a nitroxide spin-label at a sulfhydryl site, has permitted the measurement of NMR and electron paramagnetic resonance (EPR) relaxation rates to map the active and allosteric site topography. Distances from these loci to the phosphoryl of fructose 6-phosphate (Fru-6-P) and inorganic phosphate (Pi) and four nuclei of adenosine 5'-phosphate (AMP) (the phosphorus nucleus, H-8, H-2, and H-1') were obtained. These measurements located the Mn2+ approximately equidistant from the two phosphoryl moieties of the product ligands Fru-6-P and Pi and in close proximity to the AMP. The adenosine moiety of the latter is oriented anti. Analysis of EPR data revealed that the nitroxide group is approximately 16 A from the structural Mn2+ site. Calculation of the residence times for the hydrolysis reaction products suggests that their dissociation should not be rate limiting in the overall reaction cycle. PMID- 6258639 TI - Role of the beta-phosphate-gamma-phosphate interchange reaction of adenosine triphosphate in amino acid discrimination by valyl- and methionyl-tRNA synthetases from Escherichia coli. PMID- 6258640 TI - Covalent binding of thrombin to specific sites on corneal endothelial cells. AB - Binding of 125I-labeled human alpha-thrombin to endothelial cells derived from bovine corneas was studied in tissue culture. Specific and saturable binding to the cell surface occurred at 37 degrees C but to a much smaller extent at 4 degrees C. Binding of [125I]thrombin to a specific site on these cells with formation of a 77000-dalton complex was demonstrated by NaDodSO4 (sodium dodecyl sulfate)-polyacrylamide gel electrophoresis. Binding of [125I]thrombin was blocked by a 100-fold excess of unlabeled alpha-thrombin and by the thrombin inhibitor, hirudin. There are approximately 100000 of these thrombin binding sites on the cell surface. Formation of the complex could be detected as early as 15 s, increased rapidly over the next 20-30 min, and then continued at a slower rate for the next 2.5 h. The catalytically active site of the enzyme was required for formation of the NaDodSO4-stable complex as shown by the inability of diisopropyl phosphorofluoride inactivated thrombin to form stable complexes with these cells. The complex was dissociated in NaDodSO4 with 1.0 M hydroxylamine, suggesting an acyl linkage of the enzyme to the cellular binding site. The thrombin-endothelial cell complex was distinct from the thrombin-antithrombin III complex (Mr approximately 90000) on gel electrophoresis, and its formation was not enhanced by heparin. Additional thrombin-cell complexes (Mr less than 77000) were also identified; however, they represent a small fraction of the total thrombin bound to the cells. These observations demonstrate that alpha-thrombin is capable of reacting specifically with corneal endothelial cells to form a NaDod-SO4-stable complex which requires the catalytically active enzyme. PMID- 6258641 TI - The mechanism of the sodium pump. PMID- 6258642 TI - Hemoperfusion, rate of oxygen consumption and redox levels of mitochondrial cytochrome c (+c1) in liver in situ of anesthetized rat measured by reflectance spectrophotometry. AB - Utilizing reflectance spectrophotometry, hemoperfusion, rate of oxygen consumption and redox level of mitochondrial cytochrome c (+c1) in livers in situ of anesthetized rats were measured. The transition to the anoxic state was induced by raising the pressure on the liver surface to more than the hepatic blood pressure by pressing with the tip of the optical guide of the reflectance spectrophotometer. During this transition, the average oxygen saturation of hemoglobin in the liver in situ decreased linearly with time until it became 10- 20% of the total. This was followed by reduction of mitochondrial cytochrome c (+c1), which reached completion in 10--20 s. The measured O2 consumption rate remained constant until the percentage of oxyhemoglobin in situ decreased to a critical level. There was then a decrease in the rate of O2 consumption which was accompanied by a progressive reduction of cytochrome c (+c1). It was shown that amounts of hemoglobin and mitochondrial respiratory chain cytochromes in the liver in situ could be measured non-invasively and could provide important signals for vital cellular functions. The changes in hemoperfusion and rate of O2 consumption of the liver in situ following ethanol ingestion were also shown in rats, and are briefly discussed with respect to possible application of this method to study the pathophysiology of tissues. PMID- 6258643 TI - A re-evaluation of the low-temperature kinetics of the reaction of fully reduced mitochondrial cytochrome oxidase with carbon monoxide and the spectral characterization of species Ic in the Soret and visible regions. AB - The kinetics of the reaction of fully reduced membrane bound cytochrome oxidase with CO following photolysis of the fully reduced cytochrome oxidase-CO complex habe been re-examined by re-analysing the data of Clore and Chance (1978) Biochem. J. 175, 709-725) at six temperatures in the 178-203 K range simultaneously at only a single wavelength pair, 444-463 nm. The choice of the 444-463 nm wavelength pair was based on the fact that the absorbance change produced at 444-463 nm on photolysis of the CO complex is sufficiently large and the separation between monitoring and reference wavelengths sufficiently small to render the effects of any possible time dependent scattering changes insignificant. On the basis of our analysis only a two step mechanism (Model 1 of Clore and Chance (1978) Biochem. J. 175, 709-725) satisfies the triple requirement of a S.D. within the standard error of the data, a random distribution of residuals and good determination of the optimized parameters. The single step mechanism of De Fonseka and Chance (1978) Biochem. J. 175, 1137-1138) fails to satisfy all three requirements. The pure difference spectra of species Ic minus E, E minus IIc and Ic minus IIc are calculated from the computed kinetics of the individual species and repetitive slow wavelength scanning difference spectra (reaction sample minus the CO complex) taken during the course of the reaction of fully reduced cytochrome oxidase with CO at 176 K. PMID- 6258644 TI - Surface charge asymmetry and a specific calcium ion effect in chloroplast photosystem II. AB - We have used the decay kinetics of Signal IIf in Tris-washed chloroplasts as a direct probe to reactions on the oxidizing side of Photosystem II. A study of the salt concentration dependence of the rate of reduction of Z . + by the ascorbate monoanion has been interpreted by using the Gouy-Chapman diffuse double layer model and allows the calculation of an inner membrane surface charge density of 3.4 +/- 0.3 microC . cm-2 at pH = 8.0 in the vicinity of Photosystem II. We have also measured the outer membrane surface charge density at this pH in Tris- and sucrose-washed chloroplasts by monitoring the rate of potassium ferricyanide oxidation of Q-, and arrive at values of -2.2 +/- 0.3 microC . cm-2 and -2.1 microC . cm-2, respectively. From these experiments we conclude that in dark adapted chloroplasts at pH 8.0 there exists a transmembrane electric field in the vicinity of Photosystem II which arises from this surface charge asymmetry. In the presence of 10 mM monovalent salts, the transmembrane potential difference is of the order of 20 mV, corresponding to a field of 4 . 10(4) V . cm-1 (negative inside) for a 50A membrane. It is both smaller in magnitude and in the opposite direction compared to the photoinduced transmembrane field which gives rise to the 515 nm absorption change. We have also found non-double layer Ca2+ effects on the decay kinetics of Signal IIf with both charged (ascorbate monoanion) and neutral (diphenylcarbazide) donors. These results suggest a change in the environment of Z from lipophilic to hydrophilic upon specific binding of Ca2+. PMID- 6258645 TI - Resolution of two compound C-type intermediates in the reaction with oxygen of mixed-valence state membrane-bound cytochrome oxidase. AB - The reaction of mixed-valence state membrane-bound cytochrome oxidase with oxygen has been studied by difference spectroscopy with reference to the unliganded state and by the low temperature technique of Chance and coworkers. Three intermediates, compound A2 and two compound C-type components denoted C606 and C610, have been resolved in time and wavelength in the alpha region. Their optical properties are defined in the visible range. Compound A2 disappearance and compound C606 formation exhibit first-order kinetics with identical rate constants: 2.4 . 10(-3) s-1 at -94 degrees C. Compound A2 has its alpha band maximum at 590 nm and shares an isosbestic point at 595 nm with the C606 species. The alpha band of this intermediate peaks at 606 nm. Compound C610 is the real end point of the reaction and its alpha band maximum appears at 610 nm. Compound C606 is interpreted as resulting from the transfer of one electron from heme alpha 3 copper to oxygen and compound C610 as expressing a molecular reorganization due to the effect of the temperature. Structural requirements for the location of CuB in the active site are discussed. It is concluded that the three observed compounds are the only intermediates formed in the reaction between oxygen and mixed-valence state membrane-bound cytochrome oxidase. PMID- 6258646 TI - Nanosecond time-resolved fluorescence investigations of temperature-induced conformational changes in cytochrome oxidase in phosphatidylcholine vesicles and solubilized systems. AB - Intrinsic and lipid phase transition-induced conformational changes in cytochrome oxidase in phosphatidylcholine vesicle and solubilized systems were examined by the fluorescence lifetime of N-(1-anilinonaphthyl-4)-maleimide conjugated with the enzyme. The time-dependent fluorescence intensity of N-(1-anilinonaphthyl-4) maleimide attached to cytochrome oxidase was described as a triple exponential decay. Both the intrinsic and lipid phase transition-induced conformational changes were detectable in plots of the average lifetime against temperature. In most cases a peak occurred at the temperature of the conformational change. The time-dependent emission anisotropy showed that N-(1-anilinonaphthyl-4)-maleimide embedded in cytochrome oxidase in phosphatidylcholine vesicles underwent a rapid restricted wobbling within a cone. The half-angle of the cone was around 30 degrees for cytochrome oxidase in dimyristoyl phosphatidylcholine vesicles. PMID- 6258647 TI - Comparison of the redox reactions of various types of cytochrome c with iron hexacyanides. AB - The dynamic behavior of various types of cytochromes c in the redox reaction with iron hexacyanides was studied using a temperature-jump method in order to elucidate the molecular mechanism of the redox reaction of cytochromes with their oxidoreductants. Transmittance after the temperature jump changed through a single exponential decay for all cytochromes investigated. Under a constant concentration of anion, the redox reaction of various types of cytochrome c with iron hexacyanides was analyzed according to the scheme: (see formula in text) where C(III) and C(II) are ferric and ferrous cytochromes, respectively, Fe(III) and Fe(II) are ferri- and ferrocyanides, respectively, C(III) . Fe(II) is the ferricytochrome-ferrocyanide complex and C(II) . Fe(III) is the ferrocytochrome ferricyanide complex. When step B is slower than the other two steps A and C, tau 1 can be represented approximately as (see formula in text) where the bar over the variables denotes the equilibrium value. In a large excess of ferrocyanide against cytochrome, we can estimate kappa 2, kappa-2, K1 and K3 independently. In the case of horse cytochrome c at 18 degrees C in 0.1 M phosphate buffer at pH 7 with 0.3 M KNO3, the estimated parameters are kappa 2 = 100 +/- 50 S-1, kappa-2 = (3.5 +/- 1.0) . 10(3) S-1, K1 = 15 +/- 7 M-1 and K3 = (8.5 +/- 1.5). 10(-4) M. From the same experiments for seven cytochromes (cytochrome c from horse, tuna, Candida krusei, Saccharomyces oviformis, Rhodospirillum rubrum cytochrome c2, Spirulina platensis cytochrome c-554 and Thermus thermophilus cytochrome c-552), the following results can be deduced. (1) Each parameter defined in the scheme above (kappa 2, kappa-2, K1, K3) diverged beyond the error range. Above all, kappa 2 values of cytochromes c-554 and c-552 are as large as 1 . 10(4) S-1 and much larger than those for the other cytochromes (to 50 approx. 700 S-1). (2) The variance of kappa 2K1 and kappa-2/K3 are relatively less than the variances of individual parameters (kappa 2, kappa-2, K1 and K3), which suggests that the values of kappa 2K1 and kappa-2/K3 have been conserved during the course of evolution. PMID- 6258648 TI - Comparison of the EPR properties of photosystem I iron-sulphur centres A and B in spinach and barley. AB - The properties of Photosystem I iron-sulphur centres A and B from spinach and barley chloroplasts were investigated by electron paramagnetic resonance spectroscopy (EPR). Barley chloroplasts were shown to photoreduce significant amounts of centre B at cryogenic temperatures unlike those from spinach which only photoreduced centre A. Centre B in barley chloroplasts was also reduced by dithionite before centre A and the EPR spectrum of reduced centre B was obtained. Illumination of barley chloroplasts at 15 K where centre B was chemically reduced resulted in the reduction of centre A and the appearance of spectral features indicating interaction between the two reduced centres. The variation of behaviours of iron-sulphur centres A and B between species favours a scheme of electron flow for Photosystem I where either centre A or centre B act as parallel electron acceptors from the earlier acceptor X. PMID- 6258649 TI - Interactions of cytochrome aa3 with oxygen and carbon monoxide. The role of the 607 nm complex. AB - The 607 nm complex of cytochrome c oxidase, formed aerobically in the presence of CO, appears as an intermediate during the oxidation of CO to CO2 by the enzyme. Maximal steady-state formation of this complex requires oxygen, high levels of carbon monoxide, and the presence of an endogenous hydrogen donor system or the addition of small amounts of reductant (both with isolated enzyme and mitochondrial preparations). The 607 nm complex can be formed after removing CO from the mixed-valence CO complex (cytochrome a3+a2(3)+CO) by aerating the presumably CO-free product. The elements of CO are, therefore, probably not part of the 607 nm complex nor of the related "compound C" produced at low temperatures. PMID- 6258650 TI - Immunoreactive collagenase and bone resorption. AB - 1. Active mouse bone collagenase is excluded from its inhibitory antibody by preincubation of that antibody with various forms of inactive enzyme, e.g. 'procollagenase', some collagenase-inhibitor complexes or partially denatured or degraded collagenase. This property allows the detection of several enzymatically inactive forms of collagenase. 2. The accumulation of immunoreactive collagenase in the culture fluid of mouse bones occurred only in the presence of heparin and was not correlated with bone resorption induced by parathyroid hormone. These experiments provide further (see Lenaers-Claeys, G. and Vaes, G., Biochim. Biophys. Acta (1979) 584, 375-388), more conclusive evidence that the critical role in the resorption of the organic matrix of these explants may be due to another enzyme system than collagenase. PMID- 6258651 TI - Cyclic AMP binding proteins in the rat thyroid cytosol. Effects of suppression and stimulation of thyroid activity. AB - Suppression of thyroid activity by treatment of rats with thyroxine in vivo significantly decreases the relative concentration of protein kinase regulatory subunits in the thyroid cytosol. Stimulation by thyroid-stimulating hormone (TSH) in rats previously treated by thyroxine for 5 days significantly increases the relative concentration of regulatory subunits. Two species of regulatory subunits of protein kinases were separated by ion exchange chromatography. The observed modifications after thyroxine and TSH treatment affect both species of regulatory subunits to the same extent, whereas chronic stimulation by propylthiouracil for 30 days preferentially increases the type II regulatory subunit. PMID- 6258652 TI - the stability in various detergents of transferrin-transferrin receptor complexes from reticulocyte plasma membranes. AB - Transferrin-membrane protein complexes were solubilized either with 0.4% sodium dodecyl sulfate (SDS), 1% Triton X-100 or 0.5% sulfobetaine 3-14 from the plasma membranes of rabbit reticulocytes previously labeled with 125I and then incubated with 131-labeled transferrin. When the solubilized membranes were analyzed by gel filtration fractionation, marked variation in the preservation of transferrin transferrin receptor interaction was noted between the three detergents. After SDS solubilization, more than 80% of the 131I-labeled transferrin remained associated with membrane proteins with apparent molecular weight of the transferrin-receptor complexes of 1400 000 and 240 000. In contrast, after Triton X-100 solubilization only 40% of the transferrin was still complexed to membrane proteins with an apparent molecular weight of the complex of 450 000. Dissociation of transferrin from its receptor was most marked following sulfobetaine solubilization, with less than 30% of the transferrin still complexed. Following gel filtration 131I-labeled transferrin-125I-labeled membrane protein complexes were immunoprecipitated with goat specific anti-rabbit transferrin antibodies. The immunoprecipitates were analyzed under stringent dissociating conditions by two SDS-polyacrylamide gel electrophoretic techniques. In a linear 5-25% polyacrylamide gradient the 125I-labeled receptor obtained after membrane solubilization with all three detergents had an apparent molecular weight of 80 000. In contrast, in a different system using 10% polyacrylamide gel two 125I-labeled receptor components were detected wih apparent molecular weights of 90 000 and 80 000. These results demonstrate that estimates of the molecular weight of the transferrin receptor depended on the conditions of electrophoresis and suggest that the transferrin receptor is partially modified, perhaps by glycosylation. PMID- 6258653 TI - Effect of temperature on normal and SV40-transformed human fibroblasts. AB - The effect of a temperature shift from low (36 degrees C) to high (40 degrees C) temperature on human fibroblasts (IMR90) at various population doubling levels and IMR90 cells transformed by SV40 virus infection at a population doubling level of 30 (SV40/IMR90) was examined. Both IMR90 and SV40/IMR90 cells showed a decrease in cell saturation density at confluency, whereas an increase in population doubling time and protein content was noted when the cells were shifted up to 40 degrees C from 36 degrees C. The modification of IMR90 chromosomal proteins by arginyl-tRNA transferase was increased by the temperature shift, whereas NH2-terminal arginylation of SV40/IMR90 chromatin was not altered. Similarly, no appreciable change in 2-deoxyglucose uptake was noted with SV40/IMR90 cells at either temperature, although 2-deoxyglucose uptake by IMR90 cells was increased by the temperature shift. Additionally, the rate of 2 deoxyglucose uptake showed no difference between IMR90 and SV40/IMR90 cells. The above results support previous findings that environmental alterations, such as temperature shift can cause acceleration of cellular senescence. These findings also imply that cellular senescence remains fixed when viral transformation occurs and is rendered refractory to further age-associated alterations. PMID- 6258654 TI - Parathyroid hormone and isoproterenol stimulation of adenylate cyclase in rat osteosarcoma clonal cells. Hormone competition and site heterogeneity. AB - A clonal cell line from rat osteosarcoma was found to possess parathyroid hormone and isoproterenol sensitive adenylate cyclase. This study examines the relationship between the two hormones and triphosphoguanine nucleotide with respect to enzyme activation. Concentration-dependence curves, analyzed by computer-aided curve fitting, revealed: (1) in the presence of 5 microM GTP there were two apparent affinities for parathyroid hormone (Km 9 and 89 nM) and isoproterenol (Km 72 and 340 nM; (2) and two affinities for guanosine-5' (beta, gamma-imido)triphosphate (Km 0.25 and 1.3 microM); (3) hormones and guanine nucleotides reciprocally shifted each other's concentration dependence curve to the high affinity sites; (4) parathyroid hormone and isoproterenol interacting with high affinity sites competed for the same adenylate cyclase; (5) parathyroid hormone and isoproterenol, acting on low affinity sites had additive effects and also stimulated adenylate cyclase in the absence of added guanine nucleotides. The findings are consistent with (i) competition of parathyroid hormone and isoproterenol for the activation of the high (hormone) affinity complex containing: receptors, nucleotide subunit, triphosphoguanine nucleotide, catalytic unit (ii) the apparent presence of receptor-nucleotide sub-unit GDP catalytic unit complexes with low hormone affinity which are stimulated by parathyroid hormone and isoproterenol separately. PMID- 6258655 TI - Contractions of the rabbit vas deferens following sexual activity: a mechanism for proximal transport of spermatozoa. PMID- 6258656 TI - Stimulatory effect of luteinizing hormone and human chorionic gonadotropin on testicular prolactin receptor levels. PMID- 6258657 TI - Steroidogenesis in avian granulosa cells: early and late kinetics of oLH- and dibutyryl cyclic AMP-promoted progesterone production. PMID- 6258658 TI - Analysis of endocrine signals: the engineering and physics of biochemical communication systems. PMID- 6258659 TI - Interaction of methylglyoxal with poly-L-lysine. AB - The reaction of methylglyoxal with polypeptides is accompanied by an electron spin resonance absorption in the free radial region. Analysing the interaction of methylglyoxal with poly-L-lysine we found that methylglyoxal polymer formation is a major process in our system. The electron spin resonance signal seems to originate both from the polymer itself and its interaction with the polypeptide. Nuclear magnetic resonance measurements show that the methylglyoxal polymer interacts with the polypeptide via the NH groups of peptide bonds. PMID- 6258660 TI - Controlled release of biologically active compounds from bioerodible polymers. AB - This article reviews the controlled release of biologically active agents by the erosion or chemical degradation of a polymer matrix into which the agent is incorporated. Chemically bound active agents and work on steroid release from cholesterol implants are not covered. The mechanisms of polymer erosion discussed are: cross-linked scission; hydrolysis, ionization or protonation of pendant groups; backbone cleavage. Drug release studies are dealt with under each of these headings. PMID- 6258661 TI - Serotonin and endocrine rhythms. AB - The biological rhythms belong partly to the genetic patrimony and partly to the environmental patterns. The main results have been obtained on the hormonal fluctuations which are mostly controlled by the hypothalamopituitary system. Thus they include modulations of neurotransmitters activity especially serotonin. Experimental facts have been gathered in different species for ACTH, growth hormone, prolactin TSH and gonadotropins rhythms. These phenomenona are integrated in a general organization which includes sleep-waking cycle. PMID- 6258662 TI - [Elementary polysynaptic potentials of hippocampal neurons]. AB - Synaptic connections of 26 pairs of hippocampal neurons were studied in nonanesthetized rabbits by spike-triggered averaging of intracellularly recorded activity. Synchronized activity was detected in 5 pairs and considered to represent common inputs to the neurons recorded. Hyperpolarizing or depolarizing potentials with 3--4 ms latency were revealed in 3 additional pairs. These potentials are considered to be individual postsynaptic potentials (PSPs) evoked in the target neuron by spikes of the adjacent (0.5--2 mm apart) neuron. A quantum analysis of the individual PSPs was performed. The mean quantum content (0.27--0.65) and quantum size (35--200 mkV) were found to be of the same order as those of the excitatory PSPs previously recorded after intracerebral stimulation. It is concluded that most hippocampal synapses are of low efficacy. PMID- 6258663 TI - [Regulation of coronary circulation during acute experimental stimulation of emotiogenic zones of the hypothalamus in dogs]. AB - Ther coronary blood flow, arterial pressure, left ventricular pressure, frequency of cardiac contractions and resistance of coronary vessels were measured in dogs anesthetized with urethane by the end of diastole. At the 5th second after the start of the bipolar stimulation of the hypothalamic mamillary lateral nuclei (1- 4 v, 100 Hz, 2 msec, duration 45 sec) the increased resistance of coronary vessels, which changed at the 15th second after the start of stimulation to the decrease of the resistance have been reported. In some cases, the unipolar stimulation of the same hypothalamic nuclei (5--10 v, 100 Hz, 2 msec, duration 45 sec) resulted in the increased resistance of coronary vessels during the whole stimulation period. Intracoronary administration of propranolol in the presence of stimulation, both bipolar and unipolar, of hypothalamic mamillary lateral nuclei increased coronary constriction, changing the reaction of vasodilatation of coronary vessels towards the reaction of vasoconstriction accompanied by the decreased coronary flow and considerable elevation of arterial pressure. PMID- 6258664 TI - [Changes in the cyclic AMP concentration in muscle in experimental dexamethasone myopathy]. AB - A study was made of muscle cAMP content in rabbits with dexamethasone-induced myopathy. The experiments were performed in 15 male rabbits weighing 2.5--3.5 kg. Steroidal myopathy was produced by daily administration of 0.8 dexamethasone/kg body weight. Muscle biopsy was taken on experimental days 1, 3, 7 and 14. The content of cAMP was determined by radioimmunoassay. The clinical signs of myopathy occurred by day 7. The animals were immobilized day 14. The content of cAMP increased after the first administration of dexamethasone and remained unchanged till the end of the experiment. The increased cAMP content may be accounted for by dexamethasone effect on the enzymatic system that monitors the processes of cAMP activation and inhibition. PMID- 6258665 TI - [Xanthine oxidase--xanthines as a system of endogenous regulation of phosphodiesterase activity]. AB - The paper is concerned with the data indicating close interaction between xanthinoxidase (Xase) and phosphodiesterase (PDE). PDE activity can be modified by affecting the activity of Xase. This effect is mediated by changes in the concentrations of endogenous xanthines. The action of PDE inhibitors, methylxanthines, is discussed from the point of view of the above effect. The data obtained hold promise for purposeful monitoring of tissue concentrations of the cyclic nucleotides in vivo and in vitro. PMID- 6258666 TI - [Effect of acetylcholine on the cerebral microsomal Na, K-ATPase of rats of different ages]. AB - Na, K- and Mg-ATPase activity of the cerebral cortex microsomal fraction has been studied and compared in adult and old rats. The activity of Na, K-ATPase decreases while that of Mg-ATPase increases with age. The total ATPase activity remains unchanged. The effect of acetylcholine on ATPase activity has been found to be age-dependent. PMID- 6258667 TI - [Direct stimulatory action of blood serum, vitamin D3, and its hydroxy-analogs on calcium transport in the small intestine of chicks in vitro]. AB - A study was made of the effect of blood serum, vitamin D3 and its hydroxy-analogs (25-hydroxyvitamin D4. 1 alpha-hydroxyvitamin D3) on Ca2+ transport across the wall of the noninverted small sac of D-avitaminosis chicken during incubation in vitro. It was shown that blood serum from chickens fed vitamin D3 in different doses (50--20 000 IU) and at varying time (1--72 h) before sacrifice produced a marked stimulating action on the cation transport 10 min after administration into the intestinal cavity as compared with the effect produced by the serum from D-avitaminosis chickens. Administration into the intestine of vitamin D3 or its hydroxy-analogs in physiological doses (6.25--25.0 ng) also significantly stimulated Ca+ transport over 10 min of incubation. PMID- 6258669 TI - [Recovery of the sensitivity of J-41 cells to Coxsackie B3 virus by treatment with exogenous alkaline phosphatase]. AB - It has been shown that injection of G-41 cell cultures, deficient as regards alkaline phosphatase and resistant to Coxsackie B3 virus, in conjunction with exposure to an alkaline phosphatase preparation from the calf intestine results in virus reproduction. Depending on the dose administered and multiplicity of infection there occur either complete destruction of the monolayer or death of some cells with the development of cytopathic changes specific for Coxackie virus. PMID- 6258668 TI - [Effect of hyperalphalipoproteinemia on structural characteristics of plasma lipoproteins according to electron paramagnetic resonance spin probe findings]. AB - Spin probe, a stearic acid derivative, was used to study the structural features of different lipoproteins (LP) from plasma of subjects with different plasma level of high density LP (HDLP). Access of spin probe located in the internal nonpolar regions of HDLP for the reducer, ascorbic acid, was higher in hyperalphalipoproteinemia than in mean values of HDLP cholesterol concentration. An analogous effect was seen in subjects with LP of very low density. Possible causes of such differences as well as their role in biochemical reactions that proceed with LP participation are discussed. PMID- 6258670 TI - [Molecular-biological effect of thallium carbonate]. AB - The action of thallium carbonate (Tl2CO3) on rat embryonic cells was evaluated in accordance with the criterion for the formation of DNA breaks and chromosome aberrations, survival and mutagenicity of smallpox vaccine virus in these cells and on the basis of the frequency of dominant mutations in rats. Tl2CO3 produces DNA breaks whose restoration during 24 hours postincubation depends on the agent concentration. As the survival of smallpox vaccine virus exposed to Tl2CO3 decreases by a factor of 10(1) the virus mutagenicity rises 3fold. Tl2CO3 also possesses marked mutagenic activity as measured from the formation of chromosome aberrations. In the course of Tl2CO3 poisoning of males (for 8 months), followed by mating with intact females, there was a tendency to the increased total embryonic lethiality. PMID- 6258671 TI - [Organ culture of the liver of sucklings born to mice infected with viruses during pregnancy]. AB - The growth and proliferation of organ liver cultures from sucklings born to mice infected with Coxsackie A 13 virus during pregnancy have been studied. In liver explants of the experimental group of sucklings, a well defined zone of of growth, mostly of epithelial cells, was observed early, whereas the cell growth around liver explants of sucklings born to control female mice was either absent or very weak. PMID- 6258672 TI - Modulation of normal and abnormal myeloid progenitor proliferation by cyclic nucleotides and PGE1. AB - The effects of cyclic nucleotides and PGE1 upon the proliferation of normal granulocyte/macrophage progenitors were examined in in vitro systems and contrasted to the effects of these compounds on (1) granulocyte/macrophage progenitors from the peripheral blood of patients with myeolofibrosis/myeloid metaplasia (MF) and chronic myelogeneous leukemia (CML); and (2) blast progenitors from the peripheral blood of patients with acute myelogenous leukemia (AML) and acute monocytic leukemia (AMoL). Cyclic AMP was found to be a concentration dependent inhibitor of colony proliferation in all systems tested. Cyclic GMP was an inconsistent enhancer of colony proliferation in all systems in a manner which was not clearly concentration dependent. The effect of PGE1 in normal systems was highly variable depending on the culture conditions, but it was generally found to be an inhibitor of colony proliferation. Cyclic AMP, cyclic GMP and PGE1 altered the release of colony stimulating activity from adherent bone marrow cells in a manner opposite to the direct effects of these compounds on progenitor cell proliferation. Abnormalities in response to PGE1 were found in progenitors from patients with CML (deficient inhibition), AMoL (stimulation of proliferation in certain concentration ranges), and MF (enhanced proliferation). Studies on one of the patients with MF indicated that a normally responding population could be defined by density-gradient separation. These data confirm the capacity of these compounds to modulate in vitro proliferation of myeloid progenitors, and suggest that aberrations of response to PGE1 may occur in subpopulations of cells from several myeloproliferative disorders. PMID- 6258674 TI - [In its current state vaccination against poliomyelitis does not prevent the poliovirus from spreading among our population. Conclusions of a retrospective study on the distribution of poliovirus among hospitalized patients in the Liege area between 1 September 1959 and 31 December 1978]. PMID- 6258673 TI - Effect of an acute exposure of guinea pigs to NO2 on pulmonary prostaglandin dehydrogenase and angiotensin converting enzyme. PMID- 6258675 TI - [From superficial keratitis to deep keratitis: considerations on metaherpetic keratitis]. PMID- 6258676 TI - Purine receptors in the trachea: is there a receptor for ATP? AB - In guinea-pig trachea adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate (ADP), adenosine 5'-phosphate (AMP), adenosine and adenine were similarly potent in causing relaxation of the smooth muscle. This is in contrast to gut where ATP and ADP are 30 times more potent than adenosine. Studies with dipyridamole suggest that in trachea, as in gut, nucleotides are rapidly metabolized to adenosine. A polyphosphate modified analogue of ATP, the alpha,beta-methylene isostere, which resists degradation to adenosine was inactive in trachea although it is a potent relaxant in gut. This result may suggest that the intact ATP molecule is also inactive in the tracheal preparation: i.e. ATP acts only via its adenosine metabolite implying that receptors for adenosine but not ATP are present in the tissue. PMID- 6258678 TI - Interactions between morphine and the opioid-like peptides in the rat vas deferens. AB - 1 Morphine, methadone, levorphanol, pethidine, etonitazene and related morphine like alkaloids produced an increase in the electrically-evoked muscular contraction of the rat vas deferens. In contrast, the enkephalins and beta endorphin caused inhibition of the twitching. 2 The concentration of beta endorphin required to inhibit by 50% the muscular twitch was about 50 to 100 times less than that of the enkephalins. 3 Pretreatment of the vasa with morphine antagonized the inhibition of the neuromuscular transmission caused by either beta-endorphin or enkephalin. 4 Conversely, pretreatment with beta-endorphin sensitized the vasa to the increase in twitch tension caused by morphine. 5 Morphine did not alter the sensitivity to exogenously administered noradrenaline, dopamine or potassium. PMID- 6258677 TI - Decreased concentration of myocardial alpha-adrenoceptors with increasing age in foetal lambs. AB - Using [3H]-dihydroergocryptine, we identified myocardial alpha-adrenoceptor binding sites in foetal lambs and demonstrated that the concentration of receptors decreased with increasing foetal age. The presence of the receptor in the foetus correlated with the presence of myocardial alpha-adrenergic responsiveness. However, we found neither the alpha-receptor binding site nor responsiveness to alpha-adrenoceptor stimulation in the myocardium of adult sheep. PMID- 6258679 TI - Effects of vasodilator drugs, alkaline phosphatase, and cyclic AMP-dependent protein kinase on the 45calcium uptake of sarcolemmal microsomes from human umbilical arteries. AB - 1 A microsomal fraction was prepared from human umbilical arteries by differential centrifugation. The preparation was capable of an oxalate-stimulated Ca2+ uptake at a mean rate of 0.74 nmol Ca2+ mg-1 protein min-1 which could be inhibited by a Ca2+ ionophore, A 23 187, and by Tween 80. 2 The rate of Ca2+ uptake in the fraction obtained by density gradient fractionation paralleled 5' nucleotidase activity suggesting that vesicles of predominantly sarcolemmal origin were responsible for the microsomal Ca2+ uptake. 3 Cyclic adenosine 3',5' monophosphate-dependent protein kinase enhanced membrane phosphorylation but did not affect Ca2+ uptake. Preincubation with alkaline phosphatase reduced membrane phosphorylation to a greater extent than Ca2+ uptake. These data are not in favour of a close correlation between Ca2+ uptake and phosphorylation. 4 None of 15 vasodilator drugs (bencyclane, carbocromen, diazoxide, dilazep, hydralazine, indapamide, isosorbide dinitrate, methyl-isobutyl-xanthine, minoxidil, naftidrofuryl, nitroglycerine, prenylamine, sodium nitroprusside, tetracaine, and verapamil) had any effect on Ca2+ uptake at 10(-5) M. This suggests that vasodilator drugs do not act by a direct influence on the Ca2+ pumps of vascular smooth muscle cells. PMID- 6258680 TI - Morphine dependence and dopaminergic activity: tests of circling responses in rats with unilateral nigral lesions. AB - 1 Rats with unilateral electrolytic lesions involving both parts of the substantia nigra show dose-related, ipsilateral circling responses to apomorphine which are stable over time. 2 In non-tolerant rats, morphine (up to 10 mg/kg) does not elicit any circling behaviour but as tolerance develops to morphine, initially 10 mg/kg daily and then 100 ng/kg daily for about 4 months, the rats show a progressive tendency to walk more towards the side of the lesion. This behaviour is qualitatively different from apomorphine-induced circling. 3 When apomorphine (0 to 1.0 mg/kg) and morphine (10 or 100 mg/kg) are tested together, the total amounts of 'circling' are increased in an additive manner. However, after 22 h withdrawal from morphine there is a more marked increase in apomorphine-induced circling which is related to the level of dependence. 4 It is suggested that the sensitivity of striatal dopamine receptors is not altered by morphine dependence and that the increased response to apomorphine in abstinence probably reflects changes in the modulating actions of other neurotransmitter systems in the striatum. PMID- 6258681 TI - Muscarinic receptors in rat sympathetic ganglia. AB - 1 Potential changes in isolated superior cervical ganglia of the rat produced by muscarinic-receptor agonists were recorded by an extracellular ;air-gap' method.2 Muscarinic agonists produced a delayed low-amplitude ganglion depolarization, frequently preceded by a hyperpolarization. Potentials were enhanced by reducing [K(+)](o) or [Ca(2+)](o).3 Mean ED(50) values (muM) for depolarization at 25 degrees C were: oxotremorine 0.004, methylfurmethide 0.11, (+/-)-muscarine 0.24, furmethide 1.56, pilocarpine 4.81 and AHR-602 (N-benzylpyrrolidylacetate methobromide) 10.8. Responses produced by oxotremorine, pilocarpine and AHR-602 showed some characteristics of ;partial agonism'. ED(50) values (muM) for choline esters (measured in the presence of 2.5 mM hexamethonium) were: acetylcholine 3.2, methacholine 59 and bethanechol 78.4 Responses to muscarine were antagonized by hyoscine (K(I) 0.49 nM) atropine (K(I) 0.24 nM) methylscopolamine (K(I) 0.09 nM) lachesine (K(I) 0.15 nM) and (weakly) by hexamethonium (K(I) 0.2 mM). Propylbenzilylcholine mustard produced irreversible antagonism with an apparent onset rate constant of 2 x 10(5) M(-1)S(-1).5 Depolarization was accompanied by facilitation of submaximal ganglionic transmission.6 Muscarine (1 to 100 muM) initially reduced, then increased, the rate of (86)Rb(+)-efflux from isolated ganglia at both 6 and 120 mM [K(+)](o). These effects were reduced by 1 muM hyoscine.7 No consistent change in the amounts of cyclic 3',5'-guanosine monophosphate in isolated ganglia accompanying muscarinic depolarization could be detected.8 Mean against ED(50) values (muM) for contracting the rat isolated ileum were: oxotremorine 0.012, methylfurmethide 0.29, (+/-)-muscarine 0.48, pilocarpine 7.8 and AHR-602 9.9. Mean antagonist K(I) values (nM) were: hyoscine 0.17, atropine 0.34 and lachesine 0.27.9 It is concluded that ganglionic muscarinic receptors are quite similar to ileal receptors in terms of agonist ED(50) and antagonist K(I) values, and that the major difference between them lies in the greater ;efficacy' of certain agonists (pilocarpine, AHR-602 and McN A-343) on the ganglion. PMID- 6258682 TI - gamma-Aminobutyric acid agonists: an in vitro comparison between depression of spinal synaptic activity and depolarization of spinal root fibres in the rat. AB - 1 Relative molar potencies, of a range of gamma-aminobutyrate (GABA)-related agonists, for depolarization of isolated spinal roots have been compared with their potencies for depression of spontaneous synaptic activity, recorded in ventral roots of hemisected spinal cord preparations from 3 to 9-day-old rats. Both effects were sensitive to antagonism by bicuculline. 2 The depolarizing potencies of the series were not parallelled by their depressant potencies. This disparity was shown most strongly by 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3 ol (THIP) which was 20 times stronger than GABA in depolarizing root fibres and 20 times stronger than GABA in its depressant action and by (+)-cis-3 aminocyclopentane-carboxylic acid (17 times weaker than GABA on root fibres and 42 times stronger than GABA as a depressant). 3 The effect of uptake on these relative potencies is discussed and it is concluded that fibre depolarization and depression are probably mediated by different types of bicuculline-sensitive receptor. 4 The depolarizing potencies of the agonists showed a strong correlation with previously reported data for displacement of labelled GABA from in vitro rat brain membrane preparations (correlation coefficient 0.90, P less than 0.001). However, the relative depressant potencies showed no such correlation with binding data (correlation coefficient 0.50, P less than 0.05). PMID- 6258683 TI - Anti-prostatic activity of bifluranol, a fluorinated bibenzyl. AB - 1 Endocrine and anti-fertility studies were carried out on a fluorinated bibenzyl, bifluranol, in rats and mice. 2 A potent anti-prostatic activity of bifluranol was shown to be comparable to diethylstilboestrol (DES). In contrast, its oestrogenic potency by the oral route was about eight times less than that of DES. 3 In comparative short and long-term anti-androgenic and fertility studies in rats and in studies on sexual potency and reproductive performance in male mice, bifluranol given orally was shown to produce fully reversible suppression of accessory sexual structures without impairment of spermatogenesis and fertility. In contrast, DES administered in the same dose reduced spermatogenesis as well as accessory sexual glands. 4 Bifluranol lowered serum luteinising hormone (LH) levels without affecting follicle stimulating hormone (FSH). Under similar conditions DES reduces both LH and FSH levels. Since bifluranol does not antagonize androgen-induced stimulation of the prostate in castrated rats, its anti-prostatic effect is interpreted as a negative, hormonostatic feedback activity, mediated through a selective inhibition of LH secretion. PMID- 6258684 TI - Effects of metoclopramide and isoprenaline in the rat vas deferens; interactions with alpha-adrenoceptors. AB - 1 Metoclopramide (2.8 to 280 microM) augmented contractions of rat vas deferens preparations induced by field stimulation (6 Hz for 1 s). This effect was antagonized by phentolamine (0.1 microM). Metoclopramide (2.8 to 280 microM) did not affect phenylephrine-induced contractions. 2 Metoclopramide (2.8 to 280 microM) antagonized the inhibitory effects of clonidine on the contractions induced by field stimulation, but not the inhibitory effects of purine nucleosides. 3 From these results it is concluded that metoclopramide (2.8 to 280 microM) is a presynaptic alpha-adrenoceptor antagonist in the rat vas deferens. 4 Following beta-adrenoceptor blockade with (+/-)-propranolol (3.3 microM), (-) isoprenaline (0.47 to 14 microM) inhibited responses to field stimulation but not to phenylephrine. These propranolol-resistant effects of isoprenaline were antagonized by metoclopramide (2.8 to 280 microM) and by phentolamine (0.1 to 10 microM), indicating that isoprenaline may stimulate presynaptic alpha adrenoceptors in this preparation. PMID- 6258685 TI - The occurrence of postsynaptic alpha- and beta-adrenoceptors in the guinea-pig gall bladder. AB - 1 Guinea-pig gall bladder strips were contracted by (-)-noradrenaline, 10(-5) M, and by field stimulation at 5 Hz (in the absence or presence of 10(-6) M atropine) and relaxed to 10(-5) M (-)-isoprenaline. (-)-Adrenaline, 10(-5) M, predominantly contracted, but sometimes relaxed, this preparation. 2 In the presence of 10(-6) M phentolamine, contractions to (-)-noradrenaline and to (-) adrenaline were reversed to relaxations. The relaxations produced by (-) isoprenaline were unaltered. In the presence of 10(-6) M propranolol, contractions to (-)-noradrenaline increased in magnitude, relaxations to (-) adrenaline were reversed to contractions, and relaxations to (-)-isoprenaline were abolished. These results demonstrate the presence of postsynaptic alpha adrenoceptors which mediate contractions, and postsynaptic beta-adrenoceptors which initiate relaxations, in the guinea-pig gall bladder. 3 The contractile responses to continuous field stimulation for 5 min at 5 Hz in Krebs solution alone were reduced in magnitude by propranolol, 10(-6) M. In the presence of 10( 6) M atropine (added to eliminate the cholinergic component of the response), propranolol, 10(-6) M, had no effect on responses to stimulation at 5 Hz. Thus propranolol reduced the response to cholinergic stimulation in this tissue; the basis of this effect is unclear. In the absence or presence of atropine (10(-6) M), the responses to 5 Hz were smaller in magnitude in the presence than absence of phentolamine, 10(-6) M. This suggests that the responses to field stimulation of the guinea-pig gall bladder may, in part, be due to the release of endogenous noradrenaline which acts at postsynaptic alpha-adrenoceptors. PMID- 6258686 TI - Evidence for specific adenosine receptors at cholinergic nerve endings. AB - 1 An electrophysiological study was made to determine if adenosine and adenine nucleotides affect cholinergic nerve endings to frog skeletal muscle through relatively non-specific nucleotide receptors or through specific adenosine receptors. 2 Non-hydrolysable derivatives of adenosine triphosphate failed to alter the mean number of acetylcholine (ACh) quanta released by the nerve impulse (m) or the miniature endplate potential frequency (m.e.p.p.f) but N6 methyladenosine and 2-chloroadenosine, two adenosine analogues with an unsubstituted ribose moiety (R-site agonists), produced marked reductions in m and m.e.p.p.f. 3 In contrast, 2'-deoxyadenosine, a derivative with an unsubstituted purine ring (P-site agonist), generally produced increases in m and m.e.p.p.f, which further increased after removing the drug. Other P-site agonists such as 5'-deoxyadenosine (in the presence of theophylline) and 9-beta-D arabinofuranosyl adenine also increased m and m.e.p.p.f. 4 The results suggest that two types of adenosine receptors may be present at cholinergic nerve endings, one type (R-site) mediating depression and the other type (P-site) producing enhancement of ACh release. PMID- 6258687 TI - Inhibition of neuroeffector transmission by morphine in the vas deferens of naive and morphine-treated mice. AB - 1 The amplitude of excitatory junction potentials (e.j.ps) recorded intracellularly from smooth muscle cells of the mouse vas deferens varied with the strength of stimulation. Normorphine (0.4, 2 and 10 microM) shifted the stimulus-response curve to the right, without any change in slope. This shift of the curve was proportional to the concentration of the opiate in the bath. Naloxone (0.4 and 2 microM) antagonized this effect of normorphine. 2 The action of normorphine (2 and 10 microM) was studied in vasa deferentia prepared from control mice and mice that had been implanted with morphine pellets. Both groups of tissues were continuously exposed to a low concentration of normorphine (0.4 microM), to simulate the plasma concentration in the morphine-treated mice. Addition of 10 microM normorphine produced a parallel displacement of the curve in vasa deferentia from control animals, and a non-parallel displacement in tissues from morphine pellet-implanted mice. In the preparations from morphine treated mice a pronounced degree of tolerance to normorphine was observed at a low stimulus strength. 3 Naloxone (0.4 and 2 microM) had a greater effect on vasa deferentia prepared from morphine-treated animals than on tissues from control mice, when both organs were continuously exposed to 0.4 microM normorphine. The difference in the effect of the antagonist in the two groups of preparations was absent when the incubating solution contained 2 microM normorphine. 4 It is concluded that a low intensity of stimulation the e.j.ps are more readily depressed by normorphine and also the degree of tolerance displayed is larger than at a high intensity of stimulation. PMID- 6258688 TI - The effects of calcium concentration on the inhibition of cholinergic neurotransmission in the myenteric plexus of guinea-pig ileum by adenine nucleotides. AB - 1 Adenosine and the adenine nucleotides AMP, ADP, ATP, cyclic AMP, NAD, NADP and NADH produced a dose-related inhibition of the contractile response of guinea-pig ileum longitudinal muscle-myenteric plexus strips to low frequencies (less than 1 Hz) of electrical field stimulation. 2 These compounds inhibited hexamethonium sensitive contractions induced by nicotine but did not alter the responses to exogenous acetylcholine, and the acetylcholine output from the myenteric plexus was inhibited by the adenyl compounds. These findings indicate that adenine derivatives act at a presynaptic site on postganglionic cholinergic neurones. 3 The degree of inhibition produced by adenine compounds was inversely related to the calcium concentration of the bath fluid over a range of calcium concentrations (1 to 5 mM) that had no effect on the responses of the muscle to exogenous acetylcholine. 4 The inhibition produced by adenine derivatives was antagonized by theophylline and augmented by dipyridamole. Both of these interactions were sensitive to, and synergistic with, alterations of the concentration of calcium in the bath fluid. 5 The results suggest that adenine compounds inhibit acetylcholine release from the myenteric plexus by diminishing the availability of intracellular calcium ions required for neurotransmitter release. PMID- 6258689 TI - Uptake of radiocalcium by nerve endings isolated from rat brain: pharmacological studies. AB - 1 The uptake of radiocalcium by nerve-ending particles isolated from the striatum of rat brain was studied using lanthanum as a quenching agent. 2 High potassium induced calcium uptake occurred in two phases: an initial rapid phase and a late slow phase. Following preincubation with CaCl2 2.2 mmol/l for 1 h, dopamine at 1 to 2 x 10(-4) mol/l reduced the high potassium-induced calcium uptake which occurred during the initial rapid phase by 66 and 25% at 2 and 4 s of incubation, respectively, but had no effect on the late slow uptake phase. 3 Haloperidol at 1 x 10(-6) mol/l abolished the inhibitory effect of dopamine on the initial rapid phase of the high potassium-induced calcium uptake. Haloperidol per se had no effect on the calcium uptake. 4 Dibutyryl cyclic adenosine monophosphate at 2.5 x 10(-3) mol/l or prostaglandin E1 (PGE1) at 1 x 10(-5) mol/l had no effect on the initial rapid phase of the high potassium-induced calcium uptake by striatal synaptosomes. Neither of these agents affect calcium uptake by whole brain synaptosomes. 5 It appears that in the striatum, dopamine regulates the depolarization-induced influx of calcium in presynaptic nerve endings. This mechanism could constitute a feed-back inhibition for transmitter release in the striatum. PMID- 6258690 TI - Do motor-nerve terminals have gamma-aminobutyric acid receptors? AB - 1 gamma-Aminobutyric acid (GABA, 0.1 to 1 mM) had no significant effect on the amplitude, rise time, half decay time or frequency of miniature endplate potentials (m.e.p.ps) at the frog or mouse neuromuscular junctions in vitro. 2 Addition of GABA (1 mM) to preparations previously treated with 11 mM K+-Ringer did not cause any further increase in m.e.pp. frequency. GABA also failed to increase the m.e.p.p. frequency in a low Cl--Ringer. 3 GABA (0.1 to 1 mM) did not reduce the high m.e.p.p. frequency induced by veratrine (20 to 40 mg/l). 4 GABA (0.5 to 1 mM) did not affect the amplitude of the extracellularly-recorded nerve terminal spike, whereas 15 mM [K+] reduced the spike. 5 The quantal content (m) of the evoked endplate potential was not significantly altered by GABA; 9 mM [K+] significantly increased m. 6 When external d.c. potential differences were recorded in a three-chambered bath, GABA (0.1 to 1 mM) produced a very small depolarization if applied to the phrenic nerve trunk, but not if applied to the pre-terminal axon/motor nerve terminal region. Carbachol (0.3 to 1 mM) evoked a small depolarization when applied to the nerve terminal chamber. 7 These results fail to provide evidence for the existence of GABA receptors on motor nerve terminals. PMID- 6258691 TI - A study of the role of cyclic adenosine 3',5'-monophosphate in the depression by opiates and opioid peptides of excitatory junction potentials in the mouse vas deferens. AB - 1 Excitatory junction potentials (e.j.ps) were recorded with intracellular microelectrodes from smooth muscle cells of the mouse isolated vas deferens. The amplitude of the e.j.p. was used as a measure of transmitter release evoked by applying single pulse stimuli to the intramural nerves. 2 Cyclic adenosine 3',5' monophosphate (cyclic AMP) and dibutyryl cyclic AMP (db cyclic AMP, up to 1 mM) depressed the amplitude of e.j.ps, probably by interacting with extracellular sites on the nerve terminals, similar to those responsive to adenosine. 3 The phosphodiesterase inhibitors, 1-methyl-3-isobutyl xanthine (IBMX) and 1-ethyl-4 hydrazino-1H-pyrazolo(3,4-b)pyridine-5-carboxylic acid, ethylester, hydrochloride (SQ20,006) increased e.j.p. amplitude; this increase was much greater when the phosphodiesterase inhibitor was applied together with db cyclic AMP. 4 Neither the cyclic nucleotides nor the phosphodiesterase inhibitors altered the resting membrane potential of smooth muscle cells. 5 The amplitude of the e.j.p. was depressed by normorphine, D-Ala2-Met5-enkephalinamide (DAEA) and D-Ala2-D-Leu5 enkephalin (DADL) with respective EC50s of 560 nM, 49 nM and 510 pM. 6 There was no change in the EC50 for normorphine in the presence of cyclic AMP (1 mM) or in the presence of a combination of IBMX (50 microM) and db cyclic AMP (500 microM). Similarly, the depression of the e.j.p. by DAEA or DADL was not affected by the combination IBMX (500 microM) and db cyclic AMP (250 microM). 7 These findings provide evidence against the hypothesis that a reduction in cyclic AMP levels in nerve terminals is an essential step in the inhibition by opiates and opioid peptides of transmitter release. PMID- 6258692 TI - Anti-tremor action of C10Dichol, a peripheral acetylcholine synthesis inhibitor. AB - 1 Anti-tremor action of decamethylene bis-(hydroxyethyl)-dimethylammonium bromide (C10Dichol), a peripheral acetylcholine synthesis inhibitor, was investigated. 2 C10Dichol inhibited tremor induced by oxotremorine, nicotine and physostigmine and afforded partial protection from physostigmine-induced mortality in mice. 3 In non-paralysing doses, C10Dichol antagonized the neuromuscular effects of oxotremorine, nicotine and physostigmine. 4 Prior administration of C10Dichol failed to prevent tremor and neuromuscular paralysis induced by harmine and arecoline. 5 In the absence of any antimuscarinic property of C10Dichol, its neuromuscular effects appeared to be casually related to its anti-tremor action. 6 This study reveals a possibility for the development of peripherally acting anti-Parkinson drugs. PMID- 6258693 TI - Effects of ervatamine chlorhydrate on cardiac membrane currents in frog atrial fibres. AB - 1 The effects of a new alkaloid, ervatamine, on transmembrane currents of frog atrial fibres were studied by the double sucrose gap voltage clamp technique. 2 Ervatamine (2.8 x 10(-4) M) blocked the action potential without altering the resting membrane potential. 3 The alkaloid depressed the peak INa. The dissociation constant for the blocking effect of ervatamine on gNa fast was 2.35 X 10(-5) M with a one to one relationship between the drug molecule and the Na channel. Ervatamine did not alter the apparent equilibrium potential for Na, as well as the activation and inactivation parameters of gNa fast. This suggests that the alkaloid inhibitory effect on gNa can be attributed to a reduction in gNa. 4 Ervatamine prolonged the rate of reactivation of the Na system. It inhibited gNa in a frequency-dependent manner; this indicates that the alkaloid acts on open Na channels i.e. that the drug has to enter the channel or cross the membrane to produce the block. 5 Ervatamine inhibited Ina slow which occurs in Ca free, tetrodotoxin-containing solutions and moderately decreased ICa which occurs in Na-free solutions. The drug increased the background K current (IK1) and did not alter the time-dependent K current (Ix1). 6 The present study shows that ervatamine is a good inhibitor of both fast and slow gNa. This drug also shares some common electrophysiological properties with antiarrhythmic drugs namely: the frequency-dependent inhibition of the fast gNa and the ability to slow the reactivation of the Na carrying system. PMID- 6258694 TI - Antidiuretic effect of beta-endorphin and morphine in Brattleboro rats: development of tolerance and physical dependence after chronic morphine treatment. AB - 1 beta-Endorphin (2 micrograms injected into the lateral ventricles) produced a significant decrease in the urine outflow and in the excretion of Na+ and K+ in Brattleboro rats, animals suffering from severe diabetes insipidus. Morphine intracerebrally also produced antidiuresis, as compared to saline-treated controls. 2 Morphine injected intraperitoneally caused a dose-dependent decrease in the urine outflow, and in the excretion of Na+ and K+. 3. Rats chronically treated with morphine (72 h of morphine pellet implantation) were less sensitive to the antidiuretic effect of a challenge dose of morphine than control Brattleboro rats implanted with placebo pellets, but otherwise treated similarly. 4 After chronic morphine administration, Brattleboro rats became dependent on morphine. Challenge with 1 mg/kg naloxone (s.c.) precipitated an abrupt opiate withdrawal syndrome characterized, among other symptoms, by increased urination in contrast to the antidiuresis observed before naloxone. PMID- 6258695 TI - [3H]-Clonidine binding to alpha-adrenoceptors in membranes prepared from regions of guinea-pig kidney: alteration by monovalent and divalent cations. AB - 1 [(3)H]-clonidine binds reversibly to membranes prepared from regions of guinea pig kidney.2 Higher levels of binding were obtained in the membranes prepared from renal cortex (2.15 +/- 0.27 pmol/g wet wt.) than renal medulla (0.53 +/- 0.07 pmol/g wet wt.) or papilla (0.14 +/- 0.06 pmol/g wet wt.; n = 4).3 Scatchard analysis performed by addition of unlabelled clonidine (1 to 30 pmol) gave figures for the dissociation constant (K(d)) for the binding of [(3)H]-clonidine to renal cortical membranes of 9.0 +/- 0.8 nM and B(max) of 21.6 +/- 1.7 pmol/g wet wt. (n = 4). Hill plots of these data gave gradients close to unity, indicating a lack of co-operative site interactions.4 The monovalent cations, sodium and potassium, and the divalent cation, calcium, produced concentration dependent decreases in [(3)H]-clonidine binding to membranes prepared from renal cortex, the EC(50)s being respectively 25 mM, 37 mM and 23 mM.5 At low concentrations the divalent cations, magnesium (1 mM) and manganese (0.1 mM), produced enhancement of [(3)H]-clonidine binding. At higher concentrations (>10 mM) both divalent cations inhibited binding.6 Scatchard analysis of [(3)H] clonidine binding performed in the presence of sodium (100 mM), magnesium (1 mM) or manganese (0.1 mM) revealed that the alterations in binding are primarily due to changes in apparent affinity rather than a change in the number of binding sites. Sodium (100 mM) produced a change in the K(d) from 7.0 +/- 0.4 nM (n = 8) to 42.3 +/- 27.5 nM (n = 3), whereas magnesium (1 mM) decreased the K(d) to 6.0 +/- 0.9 nM and manganese (0.1 mM) to 4.0 +/- 1.0 nM (n = 3).7 The results indicate that [(3)H]-clonidine labels a binding site that has properties resembling an alpha(2)-adrenoceptor, located in the renal cortex. The changes produced by the addition of monovalent and divalent cations are entirely due to changes in the apparent affinity of [(3)H]-clonidine binding. PMID- 6258696 TI - Interaction between adenosine triphosphate and noradrenaline in the isolated vas deferens of the guinea-pig. AB - 1 An interaction between adenosine triphosphate (ATP) and noradrenaline (NA) was investigated in the isolated vas deferens of the guinea-pig. 2 ATP (1.7 to 50 microM) enhanced contractions due to transmural electrical stimulation (ES; parameters: 30 Hz, 0.2 to 0.3 ms, 10 to 30 V; 1 s train duration). Responses to exogenous NA (12 microM) were also potentiated by ATP while contractions to acetylcholine (6 microM) were inhibited. 3 NA (1.2 microM) potentiated ATP induced contractions and prevented the development of tachyphylaxis to ATP (510 microM). 4 Phentolamine (12.5 microM) prevented the potentiation by NA of ATP induced contractions; these contractions were insensitive to phentolamine (up to 25 microM). 5 Removal of potassium chloride from the Tyrode solution for 10 min abolished the potentiating actions of both ATP and NA. 6 The present results suggest that the effect of ATP may be functionally closely related to that of NA at alpha-adrenoceptors in the vas deferens of the guinea-pig. PMID- 6258697 TI - Adrenaline activation of prejunctional beta-adrenoceptors in guinea-pig atria. AB - 1. Adrenaline in a concentration of 1.0 microM depressed the stimulation-induced efflux of tritium from the guinea-pig atria incubated with [3H]-noradrenaline, whereas adrenaline in a concentration of 0.5 nM significantly enhanced the stimulation-induced efflux of tritium. This enhancement was blocked by metoprolol (0.1 microM) and thus appears to be mediated by beta-adrenoceptors. 2. In guinea pig atria incubated with unlabelled adrenaline and then with [3H]-noradrenaline, both catecholamines were released by field stimulation. In such atria metoprolol, practolol, oxprenolol or propranolol decreased the stimulation-induced efflux of tritium. These effects did not occur if the atria were incubated with unlabelled noradrenaline and then with [3H]-noradrenaline, suggesting that neuronally released adrenaline activates prejunctional beta-adrenoceptors. 3. The effect of oxprenolol in decreasing the release of tritium from guinea-pig atria, incubated with unlabelled adrenaline and then with [3H]-noradrenaline was greater in the presence of phentolamine. This may reflect the alpha-adrenoceptor blocking activity of oxprenolol. PMID- 6258699 TI - A double-blind trial of half-strength Polybactrin Soluble GU bladder irrigation in cystoscopy. AB - In an attempt to reduce post-cystoscopy urinary tract infection half-strength Polybactrin Soluble GU solution was used as the bladder irrigating fluid. Although the infection rate was markedly reduced, this just failed to be significant. However, it is believed that with a better combination of antibiotics the incidence of post-cystoscopy urinary tract infection can be significantly reduced. PMID- 6258698 TI - The effects of alpha- and beta-adrenoceptor activation on tension and membrane properties of the longitudinal smooth muscle of the chicken rectum. AB - 1. Isolated longitudinal muscle strips from the chicken rectum responded to isoprenaline, adrenaline and noradrenaline with a prolonged relaxation. The concentrations required to produce 50% of the maximum relaxation were 1.3 x 10( 8) M for isoprenaline, 1.7 x 10(-8) M for adrenaline and 10(-6) M for noradrenaline. The relaxing potency of isoprenaline is about equal to that of adrenaline, but more than 50 times that of noradrenaline. 2. Propranolol, 3.4 x 10(-6) M, blocked the isoprenaline-induced relaxation, and in the presence of this drug the responses to adrenaline and noradrenaline were converted into small, transient relaxations. The residual relaxation was blocked by phentolamine, 2.6 x 10(-6) M. 3. These catecholamines suppressed spontaneous spike discharge and produced membrane hyperpolarization. Propranolol, 3.4 x 10( 6) M, prevented the inhibitory effects of isoprenaline, and reduced but did not completely abolish those of adrenaline and noradrenaline. 4. Adrenaline and noradrenaline, but not isoprenaline, reduced membrane resistance in some preparations. 5. In the rectal muscle of the chicken, the beta-adrenoceptor mediates a prolonged relaxation and the alpha-adrenoceptor a fast and short lasting relaxation which is usually obscured by the beta-response and unmasked only after blockade of the beta-adrenoceptors. The alpha- and beta-mediated relaxations are each associated with the suppression of spontaneous spike activity. PMID- 6258700 TI - Secretin provocation tests. PMID- 6258701 TI - Insulinomas. PMID- 6258702 TI - Antibodies to hepatitis A antigen in relation to the number of lifetime sexual partners in patients attending an STD clinic. AB - Samples of serum from 421 patients attending a clinic for sexually transmitted diseases (STDs) were tested by radioimmunoassay for determination of the prevalence of antibodies to hepatitis A antigen (anti-HA). It was found that 42 . 4% of 33 homosexual men, 39 . 4% of 218 heterosexual men, and 38 . 8% of 170 female patients had positive results for anti-HA. The association between serological results and data on STD patients, using the variables of age, sexual type and preference, number of sexual partners in the preceding six months, and number of lifetime sexual partners and age, was determined statistically. The results show that the number of lifetime sexual partners is another factor concerned in the high prevalence of anti-HA. PMID- 6258703 TI - Acute viral encephalitis: its diagnosis and outcome. AB - Sixty patients with acute viral encephalitis admitted to The London Hospital in the last fifteen years have been reviewed. These consisted of 12 patients with known viral infection, 29 patients with acute viral infection of undetermined type, and 19 patients in whom an encephalitic illness followed a viral infection (post-infection encephalitis). The patients with primary viral encephalitis presented with an inflammatory brain disorder, including headaches and fever, and developed focal or diffuse neurological signs. Patients with post-infection encephalitis, usually following a 'flu'-like illness, presented with an acute neurological disturbance. The results of investigations, including virological studies, CSF examination, electroencephalography and neuroradiology, are described. Biopsy or autopsy material was available in 11 patients and these pathological findings supported the clinical classification of these patients. The mortality was highest in patients with herpes simplex virus encephalitis and lowest in patients with post-infection encephalitis. A considerable morbidity was found, not only in patients with primary viral encephalitis, but also in patients with encephalitis of unknown aetiology and post-infection encephalitis. PMID- 6258704 TI - A systematic approach to reconstructing microcircuitry by electron microscopy of serial sections. AB - To observe certain quantitative features of neuronal geometry and microcircuitry, it is necessary to reconstruct neurons from electron micrographs of serial, ultra thin sections. We describe here an approach to preparing, photographing, and analyzing moderately long series (100-500 sections). A series is prepared using an assembly line approach: one operator cuts while a second mounts ribbons of sections using various mechanical aids. Photographs are taken in the electron microscope at low magnification and high accelerating voltage. Sequential negatives are aligned using an image combiner and copied, using quasi-coherent illumination, onto 35 mm film. The resulting "movie' is mounted on a precision film transport mounted on an X-Y stage controlled by stepping motors. The movie is viewed through a high resolution video system while a video storage device and switching system permit rapid alternation between frames for comparisons. The profiles of a process in successive frames are "microaligned' by small adjustments of the transport's X-Y position. The absolute X-Y biological coordinates for each frame and the correction necessary to bring it into alignment are stored in a Z80 microprocessor as a process vector. When the movie is re-examined with the stepping motors under control of the computer, the microaligned process shows almost no frame-to-frame jitter. The process vector may be used to generate a "branch schematic' of the neuron. The microaligned profiles can also be digitized and displayed as a reconstruction using a PDP 11/34 computer. Uses of the approach are presented with examples from the cat retina and visual cortex. PMID- 6258705 TI - Tetanic stimulation increases the frequency of miniature end-plate potentials at the frog neuromuscular junction in Mn2+-, CO2+-, and Ni2+-saline solutions. AB - The effects of Mn2+, Co2+, and of Ni2+ on quantal acetylcholine (ACh) release have been studied with conventional microelectrode techniques. Increasing the [Co2+]0 or [Ni2+]0 (in the absence of extracellular Ca2+) caused an increase in miniature endplate potential (MEPP) frequency. [Mn2+]0 caused some increase in frequency at low levels, but then there was no rise as the concentration was increased further. In preparations depolarized with 20 mM K+, the MEPP frequency was a monotonically increasing function of [Co2+]0 or [Ni2+]0. In increasing concentrations of [Mn2+]0 there was an increase followed by a levelling off or a depression at higher concentrations. Tetanic stimulation of the motor nerve in solutions containing no added divalent cations or containing MgEGTA produced slight or no increases in MEPP frequency. In Mn2+-, Co2+- or Ni2+- saline solution stimulation of the motor nerve led to substantial increases in MEPP frequencies. The maximum frequency attained in Mn2+, Co2+, or Ni2+ was a power function of: (a) the duration of the tetanus; (b) the frequency of stimulation during the tetanus; or (c) the extracellular concentration of the divalent cation. During stimulation in Mn2+-saline solution the MEPP frequency reached a maximum; further stimulation led to a fall in frequency. We conclude that Mn2+, Co2+, and Ni2+ can enter the nerve terminal through a voltage-gated channel. Once within the terminal, they can stimulate quantal release by releasing Ca2+ or by causing the liberation of an activator, like H+, within the terminal. PMID- 6258706 TI - Specific [3H]strychnine binding associated with glycine receptors in bovine retina. AB - Saturable, specific [3H]strychnine binding can be demonstrated in homogenates of bovine retina. Scatchard plots revealed only one set of binding sites with a dissociation constant (Kd) of about 60 nM and a maximal number of binding sites of about 1.5 pmol/mg protein. The structural specificity of [3H]strychnine binding sites in bovine retina parallels the properties found for [3H]strychnine binding sites in the spinal cord of several vertebrates. Thus, the data do not give any evidence that specific [3H]strychnine binding in bovine retina labels taurine rather than glycine receptors and favors glycine rather than taurine as inhibitory neurotransmitter in bovine retina. The subcellular distribution of specific [3H]strychnine binding in bovine retina parallels that of sodium dependent, high-affinity uptake of glycine and taurine. All 3 parameters are mainly found in the P2 fractions of bovine retina homogenates, containing conventional synaptosomes, most abundant in the inner plexiform layer, but can also be found in the P1 fractions, containing large synaptosomes from the photoreceptor cell layer. PMID- 6258707 TI - Discrete regional distributions of thyrotropin releasing hormone (TRH) receptor binding in monkey central nervous system. AB - Thyrotropin releasing hormone (TRH) directly influences central nervous system (CNS) function, independent of its pituitary action. Although these CNS effects have been behaviorally characterized, information is not yet available on the precise regional distribution of its receptor. TRH receptor binding was examined in the monkey CNS by the radioreceptor assay for clarifying the site of TRH action. TRH was bound to brain tissue membranes via high-affinity (Kd = 5.9 x 10( 9) M) and low-affinity (Kd = 11.2 x 10(-8) M) components. TRH receptor binding varied dramatically throughout the monkey brain, with more than 40-fold variation. The limbic system contained the greatest amount of binding. The next highest areas were the cerebral cortex, hypothalamus, interpeduncular nucleus and periaqueductal gray matter of the midbrain. Receptor binding was very low or not detectable in the medial thalamus, cerebellum, brain stem, spinal cord and white matter. These data suggest that TRH has an effect on the CNS via limbic system, cerebral cortex and midbrain. PMID- 6258708 TI - Selective localization of different types of opiate receptors in hippocampus as revealed by in vitro autoradiography. AB - The visualization of opiate binding sites within the hippocampus of the rat has been achieved by means of an in vitro autoradiography. In line with the concept of multiple opiate receptors, different opioid agonists revealed a particular distribution pattern. Whereas the selective delta-receptor agonist [3H]D-Ala2,D Leu5-enkephalin specifically labelled binding sites in the CA2 area, [3H]etorphine grains displayed a uniform dense distribution throughout the pyramidal cell layers from CA1 to CA4. PMID- 6258709 TI - The postnatal development of the presynaptic grid in the visual cortex of rabbits and the effect of dark-rearing. PMID- 6258710 TI - Development from primary to augmenting responses in the somatosensory system. AB - The development from primary to augmenting responses of somatosensory (SI) cortical area to low-frequency stimulation of the ventrobasal (VB) thalamus or white matter (WM) beneath SI in VB-lesioned preparations was studied by field potential analysis and extracellular unit recording. Compared to the major postsynaptic components of the primary field response, which reverse at 0.25- 0.35 mm and whose sink extends from 0.6 to 1.8 mm, the augmenting potential reverses more superficially (0.1--0.15 mm) and its large depth-negativity is located in layers III and IV (0.4--1 mm). Augmentation is visible by the second shock of a 10/sec train; it grows from a late (15--20 msec) depth-negative wave in conjunction with the decrement of the early rapid components of the primary response. Out of 47 neurons that responded to the first shock in the 10/sec VB or WM train with early (less than 5 msec) discharges, 23 fulfilled stringent criteria for augmentation at the second shock: greater than 100% increased discharge probability and greater than 100% increased mean latency of response. The necessary condition for the generation of an augmented potential is a given temporal relation between the evoking stimulus and the declining phase of inhibition or the onset of rebound in the preceding response. The augmented potential cannot appear if the stimulus is delivered following the rebound of the preceding response. Not only this finding, but the similarity between the depth profiles of the rebound and augmenting potential suggest that the same elements are responsible for both events. While the patterns of augmenting responses to WM stimulation in VB-lesioned preparations differ slightly from thalamically evoked augmenting waves, the intrinsic cortical organization is sufficient for the development of a primary potential into augmenting responses. PMID- 6258711 TI - Reticular influences on primary and augmenting responses in the somatosensory cortex. AB - The effects of brief, conditioning trains of high-frequency pulses to the midbrain reticular formation (RF) on primary and augmenting responses of somatosensory (SI) cortex were investigated. Testing stimulation was applied to the ventrobasal (VB) thalamus or to the white matter (WM) beneath SI in VB lesioned animals. The RF-elicited EEG activation was associated with increased firing rates of SI neurons, enhanced probability of early synaptic discharges to VB or WM stimuli, and significantly reduced duration of the suppressed firing period following an afferent VB or WM volley. The diminished latency of the postinhibitory rebound under RF stimulation had the consequence that, within 10/sec shock-train, the second stimulus was delivered following completion of the rebound component and, instead of an augmented potential, generated a field response of primary-type. The dependence of the RF-induced change in augmenting potentials upon the sharpening effect exerted on the preceding inhibitory-rebound sequence was corroborated by analyzing the RF influence on neurons with different time-course of recovery from inhibition. The replacement of augmenting potentials by primary responses under RF stimulation is advanced as the mechanism behind the obliteration of spontaneously developing 'type I' spindle-waves during EEG arousal. The demonstration of RF influences on SI responses to WM stimulation in VB-lesioned animals points out the cortical level of the effects. The reticulo thalamo-cortical pathways underlying these influences are discussed. PMID- 6258712 TI - Middle- and long-latency auditory evoked responses recorded from the vertex of normal and chronically lesioned cats. PMID- 6258713 TI - The distribution of angiotensin II binding sites in rodent brain. AB - The distribution of specific angiotensin II (AII) binding capacity of several brain regions, pituitary, and adrenals was determined in 6 rodent species namely rats, mice, hamsters, kangaroo rats, gerbils and degus. Rats and mice had similar distributions with the highest levels of binding observed in the area postrema, septum and superior colliculi. Low levels were seen in the cortex, cerebellum, striatum and hippocampus. Other areas had intermediate levels. The distribution of AII binding in gerbils and degus was strikingly different from rats and mice. In these species, little or no binding could be detected in the brain. Additionally, the level of binding in degu adrenals was extremely low when compared to the binding observed in the adrenals of the other species. The distribution of AII binding sites in hamsters and kangaroo rats, although similar in some ways to rats and mice, had several major differences. Both had much higher levels of specific binding in cerebellum, striatum, and the hippocampus areas which had low levels of AII binding in rats an mice. Hamsters were the only species to exhibit significant specific binding in the cortex. The kangaroo rats had an unusual distribution of receptors with an apparent lack of specific binding in midbrain and area postrema. PMID- 6258714 TI - The contribution of increases in extracellular potassium to primary afferent depolarization in the bullfrog spinal cord. AB - To assess the extent to which depolarization by accumulated K+ contributes to the generation of primary afferent depolarization (PAD), the isolated bullfrog spinal cord was superfused with K+-rich Ringer solutions and the resultant dorsal root depolarizations were recorded extracellularly. Action potential blockade (with tetrodotoxin) did not reduce the K+-induced depolarization of primary afferents, indicating that the depolarization was generated locally in the region around the afferents. In this respect superfusion with K+-rich solutions adequately models the localized K+ accumulation which occurs physiologically during afferent activity. K+-induced depolarizations were decreased in the presence of 20 mM Mg2+; this effect was due to a direct decrease in the membrane response to K+ and not to blockade of K+-induced transmitter release onto primary afferents. The depolarization caused by a K+ concentration comparable to a maximum estimate of the K+ accumulating around afferent terminals following a single afferent volley was found to account for no more than about one-third of the DRP height. However, higher K+ levels, comparable to those resulting from high frequency afferent stimulation, caused large depolarizations of primary afferents, sometimes greater than the DRP amplitude. Therefore, K+-induced depolarization may contribute more significantly to PAD evoked by high frequency afferent activity. PMID- 6258715 TI - Development of opiate receptor binding in rat spinal cord. PMID- 6258716 TI - Evidence from lesion studies for epileptogenic and non-epileptogenic neurotoxic interactions between kainic acid and excitatory innervation. AB - The toxicity of kainic acid toward rat hippocampal neurons depends on the presence of specific excitatory afferents. Acute destruction of the critical pathway essentially abolishes the neurotoxicity of intraventricular kainic acid, but some or all hippocampal neurons continue to be destroyed by locally-injected kainic acid until the critical pathway(s) degenerates. These results support the view that kainic acid destroys hippocampal neurons in two ways: (1) by initiating a lethal status epilepticus; and (2) by interacting with certain pathways independently of on-going electrical activity within those pathways. PMID- 6258717 TI - Enhancement by GABA of glutamate depolarization-induced release from cerebellar nerve endings. AB - Cerebellar synaptosomes were superfused in the presence of D-[3H]aspartate (to label the glutamate 'reuptake pool') and [14C]glutamine (to label the 'new synthesis pool'). The depolarization-induced release of D-[3H]aspartate and of newly synthesized [14C]glutamate were potentiated by low concentrations of GABA (2--20 microM) or muscimol. The effect was probably mediated by the interaction of GABA with presynaptic GABA receptors localized in 'glutamergic' nerve endings, since it was antagonized by the GABA antagonists picrotoxin and bicuculline. PMID- 6258718 TI - Catecholamine is released from non-synaptic cell-soma membrane: histochemical evidence in bullfrog sympathetic ganglion cells. PMID- 6258719 TI - Mepacrine treatment prevents immobilization-induced desensitization of beta adrenergic receptors in rat hypothalamus and brain stem. AB - Forced immobilization is a severe stress in rats which diminishes levels of epinephrine in specific nuclei in the hypothalamus and brain stem, suggesting that release of epinephrine is stimulated to a rate which exceeds the rate of its replacement. In the pineal gland, frog erythrocytes, C6 astrocytoma cells and rat brain, beta-adrenoceptor agonists appear to regulate the number of their receptors. Exposure to high concentrations of an agonist leads to apparent decrease in receptors reflected by a decrease in maximal specific binding of antagonists. The apparent decreases in receptors have been shown to be attended by decreases in physiologic responsiveness. In C6 astrocytoma cells, beta agonists stimulate methylation of phosphatidylethanolamine to increase formation of membrane phosphatidylcholine which in turn appears to enhance activation of adenyl cyclase. Interference with the metabolism of phospholipids by exposure to phospholipase A2 inhibitor, mepacrine (quinacrine), prevents agonist-induced desensitization of beta-adrenoceptors in astrocytoma cells. In the present study repeated immobilization stress has been found to decrease significantly the number of beta-adrenoceptors in hypothalamus and brain stem while increasing the number of alpha 2-adrenoceptors. The desensitization of beta-adrenoceptors was prevented by treatment with mepacrine. PMID- 6258720 TI - The action of norepinephrine in the rat hippocampus: intracellular studies in the slice preparation. AB - The ionic basis of norepinephrine (NE) action was studied with intracellular recording techniques in the rat hippocampal slice. Topical application of NE caused, in CA1 neurons, a 3-4 mV hyperpolarization associated with a 10-20% decrease in input resistance. This effect was accompanied by a decrease in spontaneous action potential discharges and, in some cells, by a reduction in EPSPs produced by stimulation of the excitatory Schaffer collateral-commissural pathway. An analysis of the voltage and concentration dependency revealed that NE may activate two different mechanisms. Experiments performed to test this hypothesis have demonstrated that a short duration hyperpolarizing action of NE was still present in a low Cl- medium. The hyperpolarizing responses to NE were absent in ouabain-treated slices and in low temperature. Cyclic AMP produced a 3 4 mV hyperpolarization associated with minimal changes in input resistance. This effect of cAMP was blocked by ouabain. IBMX potentiated responses to low concentrations of NE. It is proposed that NE activates two mechanisms; one involves activation of Cl- conductance and the other activation of a Na+-K+ pump. This latter effect might be mediated by cAMP. PMID- 6258722 TI - The neurolathyrogen, beta-N-oxalyl-L-alpha,beta-diaminopropionic acid, is a potent agonist at 'glutamate preferring' receptors in the frog spinal cord. AB - A neurotoxic amino acid, beta-N-oxalyl-L-alpha,beta-diaminopropionate (beta ODAP), found in seeds of Lathyrus sativus and a possible causative agent of neurolathyrism, was equipotent with kainate as a depolarizing agent of frog spinal cord ventral roots. beta-ODAP and kainate appeared to act on a common receptor, as their actions could not be differentiated pharmacologically. These results could explain some of the symptoms of neurolathyrism. PMID- 6258721 TI - Differentiation of kainate and quisqualate receptors in the cat spinal cord by selective antagonism with gamma-D(and L)-glutamylglycine. AB - The D and L forms of the dipeptide, gamma-glutamylglycine depress NMDA-, L aspartate- and kainate-induced excitation in cat spinal cord while little or nor effect on L-glutamate- and quisqualate-induced responses. The dipeptides also depress dorsal root-evoked excitation of Renshaw cells, but not acetylcholine- or ventral root-evoked excitation of these cells. The D form of the dipeptide is more potent than the L form. The results are interpreted in favour of three types of receptors for excitatory amino acids on spinal neurones, these being sensitive to the selective agonist action of NMDA, kainate and quisqualate. PMID- 6258723 TI - Benzodiazepine receptors in chick retina: development and cellular localization. AB - Benzodiazepine receptors are present in high concentration in the chick retina. Their pharmacological properties are similar to those of the benzodiazepine receptors present in the brain. The retina receptors appear prior to, as well as during, the period of synaptogenesis. In the newborn chick retina the receptors are localized in the inner synaptic layer, probably on or close to synaptic connections. PMID- 6258724 TI - Depression of cortical Na+, K+-ATPase activity in rats exposed to hyperbaric oxygen. PMID- 6258725 TI - The excitatory action of acetylcholine on hippocampal neurones of the guinea pig and rat maintained in vitro. AB - In preliminary experiments on 39 identified pyramidal cells in the in vitro slice preparation of the guinea-pig hippocampus the depolarization evoked by acetylcholine (ACh) applied by microiontophoresis was always associated with an increase in membrane resistance. In 9 slices cut from the rat hippocampus similar results were obtained from 24 cells. In a more detailed analysis on 13 cells from the rat hippocampus, whose mean resting potential was -74 mV and mean resting input resistance 33 M omega, the mean peak depolarization evoked by ACh was 11.6 mV and the mean increase in membrane resistance 12 M omega. The reversal potential for the excitatory action of ACh was 29 mV more hyperpolarizing than the resting membrane potential. The depolarization evoked by ACh was linearly related to the corresponding increase in membrane resistance expressed as a fraction of the resting membrane resistance determined before and after the application of ACh. This was true throughout each of the individual applications of ACh and of the peak response evoked by each of the 13 applications. The constancy of this relationship is compatible with the usual model used to describe synaptic events thought to be mediated by the closure of ionic channels which are open in the absence of the transmitter. The onset of the response to ACh was always approximately 4 times slower than that evoked by a near equipotent microiontophoretic application of glutamate from an adjacent barrel of the same multibarrelled micropipette. Following the application of ACh, recovery was also slow and, on average, was approximately 10 times longer than that following a near equipotent application of glutamate. It is suggested that the slow onset and offset of the responses evoked by ACh are not compatible with models based on diffusion and are best explained by postulating a sequential generation of one or more intermediates. PMID- 6258726 TI - Electron microscopic observations of terminals of functionally identified afferent fibers in cat spinal cord. AB - Using the method of intra-axonal injection of horseradish peroxidase, functionally identified afferent fibers from three slowly adapting (Type I) receptors and one Pacinian corpuscle in the glabrous skin of the hind paw of the cat were stained. Electron microscopic observation of the terminals of these fibers revealed predominantly axodendritic asymmetric synapses containing round, clear vesicles. Multiple synapses on a single dendrite were observed, separated by as little as 900 mm from one another. PMID- 6258727 TI - Nigro-reticular pathway in the rat: an intracellular study. AB - Stimulation of substantia nigra produced short latency excitatory and inhibitory post-synaptic potentials in neurons located in nucleus reticularis gigantocellularis in the reticular formation. These post-synaptic potentials were considered to be monosynaptic on the basis of constant latency at varying stimulus strength. It is suggested that substantia nigra is the source of the inhibition and that excitatory potentials are due to stimulation of cortico reticular fibers. PMID- 6258729 TI - Latency in the ascending auditory pathway determined using continuous sounds: comparison between transient and envelope latency. AB - The gross responses from the cochlea (round window) and two nuclei of the ascending auditory pathway of the rat in response to tone and noise bursts (compound action potentials) were compared with those recorded in response to continuous tones and noise that was amplitude modulated with pseudorandom noise. The cross-correlation function between: (1) the averaged response to the sounds that were amplitude modulated with the pseudorandom noise, and (2) one period of the pseudorandom noise, were obtained. The compound action potentials and the cross-correlation functions both had a series of peaks. The two functions had a similar morphology. The latency of the peaks in the cross-correlation showed less dependence on sound intensity than did the latency of the peaks in the compound action potentials. PMID- 6258728 TI - Effects of isoproterenol on the development of beta-adrenergic receptors in brain cell aggregates. AB - The development of binding sites for the beta-adrenergic receptor antagonist [125I]iodohydroxybenzylpindolol in reaggregate cultures of fetal rat brain has been investigated. beta-Adrenergic receptor density increased rapidly between 6 and 22 days in culture at which time maximal density was attained. When cultures were grown in the presence of the beta-adrenergic receptor agonist isoproterenol, the development of receptors was markedly inhibited. Cultures were also grown for 15 days in the presence of isoproterenol and then for 7-14 days in the absence of isoproterenol. Following the removal of the agonist, binding sites developed, but to only approximately 50% of the density seen in control cultures. PMID- 6258730 TI - GABA as the pallidothalamic neurotransmitter: implications for basal ganglia function. AB - GABA levels, high affinity GABA uptake and glutamic acid decarboxylase levels are reduced in rat ventroanterolateral thalamic nucleus after destruction of the entopeduncular nucleus with kainic acid. This is strong evidence that GABA is an entopedunculothalamic neurotransmitter. The striatoentopeduncular pathway is also GABAergic. Thus the function of the corpus striatum may be to disinhibit the thalamus. PMID- 6258731 TI - Stimulation-dependent uptake of glutamic acid by hippocampal slices. PMID- 6258732 TI - Calcium dependence of synaptic transmission in the hippocampal slice. AB - 'Population' afferent spike and 'population' EPSP were recorded with extracellular microelectrodes in slices of hippocampal tissue maintained in vitro. Calcium concentration was changed in the bathing solution, and calcium activity ([Ca2+]0) was measured in interstitial fluid of the slice with ion selective microelectrodes. Synaptic transfer was a non-linear continuous function of [Ca2+]0. Deviation of [Ca2+]0 by 0.1 mM from the 1.2 mM control level caused a change of approximately 15% in the slope of the input-output function. PMID- 6258733 TI - Evidence that the opiate receptors of the substantia gelatinosa contribute to the depression, by intravenous morphine, of the spinal transmission of impulses in unmyelinated primary afferents. AB - In barbiturate anaesthetized cats, dorsal horn neurones were excited by electrical stimulation of the common tibial nerve. The numbers of action potentials evoked by excitation of C fibres were depressed by analgesic doses of morphine (1-4 mg/kg i.v.). Naloxone, administered electrophoretically in the substantia gelatinosa, fully reversed the inhibitory action of morphine. The results suggest that opiate receptors in the substantia gelatinosa play a role in morphine analgesia. PMID- 6258734 TI - Diphenylhydantoin reduces the outward current of the action potential in Aplysia. AB - Diphenylhydantoin (DPH) has been shown to prolong the repolarization phase of action potentials in Aplysia and to reduce the spike after hyperpolarization. We voltage-clamped somata of Aplysia giant neurons and measured the action potential currents to determine what alterations might be responsible for the prolonged repolarization and reduced undershoot. DPH did not affect the peak inward current; however, it did reversibly reduce the outward current at concentrations of 38 microM or greater. The data indicate that DPH reduced the voltage sensitive potassium conductance rather than the 'A' current or the calcium activated potassium conductance. These changes in outward current would explain the prolonged action potentials and reduced afterhypolarization seen with DPH in Aplysia. PMID- 6258736 TI - Neuronal maturation in mammalian cell culture is dependent on spontaneous electrical activity. AB - Fetal mouse spinal cord (SC) and dorsal root ganglion (DRG) neurons undergo a process of maturation in cell culture lasting a month or more. We have investigated the role of electrical activity in this maturational process with the use of tetrodotoxin (TTX), the specific blocker of the voltage-sensitive sodium channel responsible for action potential generation. This agent completely eliminates the spikes and related synaptic activity which occur abundantly in untreated cultures. Such blockade of electrical activity in the cultures, when begun early (day 1 or day 8 in vitro), results in a 85-95% reduction in the number of large SC neurons, without affecting DRG neuron numbers. TTX treatment initiated when cultures are mature (day 70) has no significant effect on either DRG or SC neurons. Intermediate effects are obtained when treatment is initiated at day 35 in vitro. The activity of the nerve-specific enzyme choline acetyltransferase, is significantly decreased by early TTX treatment, while DNA and protein content of the cultures (primarily contributed by glial and fibroblastic cells) is not affected. PMID- 6258735 TI - Ascorbic acid inhibition of Na,K-adenosine triphosphatase of rat forebrain without peroxidation of membrane lipids. AB - Using reagents and membrane preparations from which contamination had been carefully removed, we found that ascorbic acid inhibited rat brain Na,K-ATPase without causing lipid peroxidation, unlike the conventional belief; the inhibition was prevented by catecholamines and EGTA. Ascorbic acid radicals, instead of active oxygen, may play a role in the inhibition. PMID- 6258737 TI - Temporal and spatial response characteristics of the cat superior colliculus. AB - We have examined the responses of 72 cells of the cat superior colliculus to drifting gratings of sinusoidal luminance profile as a function of spatial frequency velocity and contrast. Of 72 cells, 66 responded to gratings either by change in mean firing rate only (58/72) or in a temporally modulated pattern in addition to the change in mean firing rate (8/72). The remaining 6 showed no change in discharge rate in response to any of the gratings tested. Many cells (24/72) were inhibited or excited by particular combinations of spatial and temporal frequencies. Some (8/72) demonstrated selective inhibition or excitation to a particular temporal frequency independent of spatial frequency and velocity and could therefore be said to be tuned specifically to temporal frequency. No cells were tuned only to a constant spatial frequency or a constant velocity. (24/72) cells displayed maximum inhibition or excitation only at a particular combination of spatial and temporal frequencies. Some cells (8/72) demonstrated a temporal modulation synchronous with the drifting grating in addition to an elevated mean discharge rate. The change in discharge rates evoked by gratings are generally less than those evoked by presentation of moving small slits or spots of light. Collicular cells often demonstrate a center-surround organization in their response to gratings. The center and surround often differ in their spatial frequency and velocity preferences. Compared to cortical and retinal ganglion cells, individual collicular cells are extremely non-linear. On a cell population basis, however, a linear Fourier analysis on grating response predicts the collicular cells' preference for movement of small objects. PMID- 6258739 TI - Rat brain cells in primary culture: characterization of angiotensin II binding sites. AB - The binding kinetics of angiotensin II (ANG II) have been studied in primary cultures from fetal rat brain. Binding of [125I]ANG II to rat brain cells in culture is time-, pH- and cell concentration-dependent. The binding is saturable, reversible, and 90--95% specific. Binding follows first-order kinetics, with values for K1 and K-1 of 4.9 x 10(6)M-1 S-1 and 3.33 x 10(4)S-1 respectively. Scatchard analysis reveals the presence of a single class of binding sites with Ka of 1.0 x 10(9)M-1 and an average of approximately 6 x 10(3) sites per cell. [125I]ANG II recovered from incubation medium under the conditions of the binding assay or after dissociation from cells is not significantly degraded as judged by gel filtration on Sephadex G-25 and radioreceptor assay. ANG II analogs compete with [125I]ANG II for binding, with potencies in general paralleling previously established biological activities. Of 5 analogs tested, (Ile8)-ANG II was almost equipotent with ANG II while (Dval3)-ANG II was least potent in the competitive binding assay. These data fulfill criteria for the identification of specific angiotensin II receptors in cells from mammalian brain. PMID- 6258738 TI - Enhanced parallel fiber frequency-following after reduction of postsynaptic activity. AB - The frequency-following capabilities of the parallel fibers (Pf) of the rat cerebellar cortex were studied in the presence and absence of surround synaptic activity. When synaptic potentials were reduced or eliminated by local superfusion of the cerebellum with calcium antagonists or when they were reduced following a stimulation train, the Pfs showed more reliable frequency-following. Enhancement of synaptic activity with 4-aminopyridine (4-AP) application leads to a decrease in the frequency-following capabilities of the Pfs. When calcium antagonists were added to the 4-AP superfusate the synaptic enhancing effect of 4 AP was obliterated, and the Pfs displayed more reliable frequency-following capabilities. In addition, an extracellular slow potential was monitored and described in relation to the amplitude of the parallel fiber volley. We interpret these results to indicate that changes associated with postsynaptic activity of molecular layer neuronal elements may influence the frequency-following properties of presynaptic elements, i.e. the parallel fibers, possibly via an extracellular pathway. PMID- 6258740 TI - A comparison of the effects of pentobarbital and diphenylhydantoin on the GABA sensitivity and excitability of adult sensory ganglion cells. AB - The actions of pentobarbital (PB) and diphenylhydantoin (DPH) have been studied on neurons of dorsal root ganglia from adult rats. At anesthetic level (i.e. 1--2 x 10(-4) M), PB greatly enhanced neuronal responses to gamma-aminobutyric acid (GABA); at 10(-3) M PB caused a small depolarization and profoundly attenuated GABA responses, probably because of cross-desensitization of GABA receptors. In contrast to results in some non-mammalian species, DPH (up to 2 x 10(-4) M) did not affect GABA responses under any conditions. PB depressed single intracellularly evoked action potentials only at high concentrations, but the cell's ability to fire trains of impulses in response to prolonged depolarization was impaired (i.e. accommodation was enhanced) at the anesthetic dosage level. DPH (1--2 x 10(-4) M) selectively depressed sodium-dependent action potentials of tetrodotoxin (TTX)-sensitive cells, and also impaired their ability to fire repetitively, but it did not influence sodium conductances and other aspects of excitability of TTX-insensitive neurons. In addition, both DPH and TTX reversed neuronal depolarizations induced by veratridine. Calcium-dependent potentials appeared to be unaltered by DPH. The results suggest that the anesthetic properties of PB may depend, in part, upon the enhancement of GABA-mediated inhibitions and increased accommodation. The anticonvulsant DPH exerts a selective, TTX-like depression of sodium conductances which does not extend to sodium conductances which are insensitive to TTX. PMID- 6258741 TI - Changes in noradrenergic transmission alter the concentration of cytoplasmic progestin receptors in hypothalamus. PMID- 6258742 TI - Circadian and seasonal rhythms in alpha- and beta-adrenergic receptors in the rat brain. AB - Circadian rhythms in the numbers of alpha- and beta-adrenergic receptors exists in the rat forebrain and hypothalamus. These rhythms are endogenous as they persist in the absence of time cues. The alpha- and beta-receptor rhythms differ both in their shapes (wave form) and in the timing (phase) of the peak numbers. In the course of the year, there are shifts in the timing of both alpha- and beta receptor peaks. Circadian rhythms in synchronizing both the synaptic events and the behaviors related to them to the photoperiod of the natural environment. PMID- 6258743 TI - Negative slope conductance at large depolarizations in cat spinal motoneurons. AB - The current-voltage relation of cat spinal motoneurons obtained by somatic voltage clamp exhibits a region of negative slope conductance at large depolarizations in addition to the previously reported N-shaped region at small depolarizations. The N shape at large depolarizations is caused by one outward current component which grows larger and then smaller with depolarization. PMID- 6258744 TI - Is aspartic acid the neurotransmitter of the perforant pathway? AB - In order to determine whether an amino acid may act as a neurotransmitter in the perforant pathway we examined the effect of lesion of rat entorhinal cortex on the concentrations of various amino acids in the hippocampus proper and fascia dentata. Only the aspartic acid content was found significantly decreased after the lesion. This decreases is not due to a loss from target cells of the perforant pathway, but rather to a loss from its degenerating terminals. PMID- 6258745 TI - Modulation of arterial muscle contraction in Aplysia by glycine and neuron R14. AB - Glycine and electrical activity in neuron R14 both enhance the contractility of the anterior aorta of the gastropod Aplysia californica. Glycine and R14 do not seem to cause contraction directly, change membrane permeabilities or alter junctional potentials occurring in the muscle fibers, yet they increase the force of contractions induced by other means. Modulation of muscle contraction is a new function for glycine. PMID- 6258746 TI - Amphetamine-induced motility and nigrostriatal impulse flow. PMID- 6258747 TI - Effects of naloxone and hypophysectomy on electroconvulsive shock-induced analgesia. AB - Powerful analgesia follows electroconvulsive shock in both hypophysectomized and sham-operated rats. Antagonism of this analgesia by naloxone implicates opioid peptides in its mediation, its occurrence in hypophysectomized animals implicating opioids of central nervous system rather than pituitary origin. Because naloxone only partially reduces electroconvulsive shock analgesia in hypophysectomized rats, the participation of another, non-opioid analgesia substrate also seems indicated. PMID- 6258748 TI - Naloxone-reversible duplication by lanthanum of opiate analgesia effects on orofacial, lower body and central nociception. PMID- 6258749 TI - Triplicated bursting neuron R15 in an Aplysia abdominal ganglion: non-symmetrical coupling, common synaptic inputs and response to dopamine. AB - An abdominal ganglion of the mollusc Aplysia californica was found to contain 3 neurons in the place normally occupied by a single R15 cell. The 3 neurons exhibited properties characteristic of R15 neurons including spontaneous bursts. The bursts appeared asynchronously in spite of electrotonic coupling between them. The coupling function approximated a low pass filter with a cut-off frequency between 0.02 and 0.05 Hz in accordance with a measured coupling time constant of 5--10 sec. Coupling measured in the cell body was found to be stronger for hyperpolarizing currents than for depolarizing currents injected into any of the 3 cells. This 'symmetrical rectification' can be explained by a rectifying axonal membrane interposed between the site of coupling and the site of recording. All 3 cells were found to have dopamine receptors and to receive common synaptic inputs. Since the coupling efficiency was found to vary depending on the direction of current flow, depolarizing synaptic inputs and spike burst generation remain autonomous. PMID- 6258750 TI - Development of glutamate binding sites and their regulation by calcium in rat hippocampus. AB - The postnasal development of the Na-independent [3H]glutamate binding sites, which exhibit some characteristics of postsynaptic glutamate receptors, has been studied in rat hippocampal membranes. The amount of binding sites (expressed in pmol/hippocampus) represents 4% of the adult level at postnatal day (PND) 4, increases very rapidly until PND 9, and then increases at a slower rate reaching 80% of the adult value at PND 23. In contrast, the density of binding sites (expressed in pmol/mg protein) exhibits a maximum at PND 9 and slowly decreases to reach the adult value at PND 23. These changes seen to be only quantitative since the affinity (about 450nM) and Hill coefficient (about 1.0) of these binding sites remain constant throughout development. Calcium ions have been shown to markedly stimulate [3H]glutamate binding in adult hippocampal membranes. This effect appears on PND 9--10 and increases rapidly until PND 16 when it is similar to that seen in the adult rat. We also determined the minimum age at which long-term potentiation (LTP) of synaptic transmission could be detected in the CA1 field of hippocampal slice preparations following repetitive electrical stimulation of the Schaffer-commissural pathways. LTP was only rarely detected at PND 8 whereas it could be reliably obtained after PND 9. These results indicate that the postnatal development of Na-independent glutamate binding sites closely parallels synapse formation in the hippocampus, further supporting the idea that the binding sites are associated with a physiological receptor. They also show that the appearance of the stimulatory effect of calcium on glutamate binding occurs at a time when several forms of synaptic plasticity appear in the hippocampus. In particular the correlation of the development of LTP with the calcium-stimulation of glutamate binding suggests that these phenomena have similar cellular mechanisms. PMID- 6258751 TI - Histamine actions on activity of cultured hypothalamic neurons: evidence for mediation by H1- and H2-histamine receptors. AB - Tuberal hypothalamic tissue cultures were used to investigate the actions of histaminergic agents on neuronal activity using extracellular glass micropipettes. Histamine and H1- and H2-agonists were applied locally onto single active neurons by iontophoresis, while histaminergic antagonists were perfused through the bathing medium. Peri-event histogram and ratemeter analysis showed histamine to both excite and depress unit activity. Excitations were only antagonized by putative H1- and not H2-histamine antagonists, whereas inhibitions were antagonized by H2- and H2-antagonists. Dimaprit, a specific H2-agonist, elicited inhibitions of activity, while 2-(2-pyridyl)ethylamine, a putative H1 agonist, elicited both excitations and inhibitions. Two pharmacologically distinct populations of histamine receptors may exit in the hypothalamus: excitatory H2-receptors and inhibitory H2-receptors. PMID- 6258753 TI - Activation and lateralization of sensorimotor field for perioral biting reflex by intranigral GABA agonist and by systemic apomorphine in the rat. AB - In Experiment 1 unilateral injection of the GABA agonist, muscimol (20 ng in 0.1 microliter saline) into the substantia nigra (SN) of rats elicited contraversive turning and a correlated transient asymmetry in responsiveness to tactile stimulation of the mouth area. On the side of the face contralateral to the injected SN they responded stronger than on the ipsilateral side, and, furthermore, they responded to tactile stimulation with a withdrawal of the lip, followed by a vigorous biting of the probe. In Experiment 2, systemic injection of apomorphine also sensitized the perioral biting response to tactile stimulation. Unilateral injection into the SN of 8 micrograms 6-OHDA blocked this response to stimulation of the side of the face ipsilateral to the lesion. The experiments demonstrate: (1) pharmacological control of sensory-motor neglect, the asymmetry being determined by the direction of turning; and (2) a possible neuropharmacological basis of the perioral biting reflex, which may be related to certain types of aggressive behaviors. PMID- 6258752 TI - Alteration in adenylate cyclase response to aminergic stimulation following neonatal x-irradiation. AB - X-irradiation of the rat neonatal hippocampus produces severe alterations in the architectonic features of the mature hippocampus. The most prominent alterations is a marked depletion of the granule cells of the dentate gyrus, with a subsequent realignment of CA 4 cells. The present data also show that norepinephrine (NE), dopamine and histamine stimulation of adenylate cyclase activity is severely attenuated in the hippocampi of irradiated animals. This failure suggests that the NE fibers of irradiated subjects, although normal in content of NE, are not functional in some of their NE-effector actions. PMID- 6258754 TI - Spontaneous activity of mediobasal hypothalamic neurons following deafferentations and lesions. AB - In view of the role of extrahypothalamic influences on the hypothalamic regulatory activity, the effects of anterior, anterolateral or posterolateral hypothalamic deafferentations and bilateral medial forebrain bundle (MFB) lesions on the spontaneous single cell activity of neurons in the mediobasal hypothalamus (MBH) were studied in rats under urethane anesthesia. While the deafferentation and particularly the anterior cuts reduced the average rates, MFB lesions increased the rate of firing of MBH neurons, and revealed cyclic activity. These data indicate that normally anterior afferents have mainly a facilitatory, while the MFB projections to the MBH have an inhibitory effect on the spontaneous activity. The possible relation of these alterations to neuroendocrine changes are discussed. PMID- 6258755 TI - Cyclic nucleotides in the amygdala of the kindled rat. AB - The basolateral amygdala of rats was stimulated once daily until three successive fully kindled seizures were elicited. Twenty-four hours after the last seizure the rats were sacrificed by focused microwave irradiation to the head. Tissues from homolateral and contralateral amygdala and cerebral cortex were assayed for cAMP and cGMP content. No significant changes in cyclic nucleotides were measured in the kindled animals. These studies indicate that long term changes in the steady-state level of total tissue cyclic nucleotides do not occur concomitant with the persistently altered excitability associated with kindling of the amygdala. PMID- 6258756 TI - Infundibular ACTH can be excluded as a critical mediator in social behaviours. AB - Kainic acid lesions of the infundibulum resulted in a significant decrease in infundibular ACTH concentrations. However, the lesioned rats did not differ from the vehicle-injected controls in a social interaction test, in their latency to start drinking in a novel environment, or in their aggressive behaviour in home cage intruder tests. It can therefore be concluded that endogenous infundibular ACTH does not play a significant role in these behaviours. This can be contrasted with the effects of exogenously administered ACTH which has previously been shown to reduce social interaction and increase aggression. Both the lesioned rats and the controls showed decreased social interaction after ACTH administration, and therefore the infundibulum can be excluded as a critical site of action of exogenous ACTH in mediating this behavioural change. PMID- 6258757 TI - Differences in cutaneous sensory response properties of single somatosensory cortical neurons in awake and halothane anesthetized rats. AB - The major aim of this study was to investigate the effect of halothane anesthesia on different latency components of cutaneous sensory responses of single units in the primary somatosensory (SI) cortex of rats. Quantitative studies of computer generated post-stimulus time histograms were used to determine whether the increase in "nonspecific" properties often observed in the SI cortices of awake animals were attributable to a generally increased sensory responsiveness of these cells or to a selective increase of certain "nonspecific" components of their sensory response. Sensory "specificity" was investigated here by measuring the size of cutaneous receptive fields of single cells and testing their ability to follow high stimulus frequencies. Histograms generated by repetitive touch stimulation of the forepaw in awake animals were divisible into the following different latency components: (1) a short latency excitatory response which was often divisible into two peaks (E1a and E1b), and occasionally (2) a post excitatory inhibitory phase (I1) and/or (3) a long latency excitatory peak (E2). In anesthetized animals spontaneous discharge rates were lower and the proportion of cells exhibiting either pure inhibition or post-excitatory inhibition was increased. By contrast, the longer latency excitatory components (E1b and E2) were weaker and were seen much less frequently than in the awake situation. In nine cells tested in the awake state and then again in the anesthetized state the magnitude, receptive field size, and ability to follow high frequencies of the E1a peak was slightly reduced. The E1b and E2 peaks seen in the awake state, on the other hand, were completely abolished by anesthesia. In awake animals the E1b and E2 phases exhibited relatively "nonspecific" physiological properties. This was indicated by the facts that: (1) the cutaneous receptive fields of the E1a peak were slightly smaller than those of the E1b peaks and much smaller than those of the E2 peaks, and (2) the E1a peak was able to follow higher frequencies of touch stimulation than the E1b or E2 peaks. It is concluded therefore that although halothane anesthesia slightly depressed the short latency response component (E1a) exhibiting highly sensory properties, its main effect was to depress the longer latency excitatory components (E1b and E2) which exhibited relatively "nonspecific" properties. PMID- 6258758 TI - The role of the medial forebrain bundle in the mediation of the hypothalamic hypophyseal-adrenal responses to acute neurogenic stress. AB - Adult male rats, intact (N) or bearing bilateral lesions in the medial forebrain bundle (MFB), were acutely exposed to visual, audiogenic, or thermal stress, during the following which serum ACTH and corticosterone (CS) levels were determined. The marked elevations in serum concentrations of both ACTH and CS which occurred in intact animals following photic stimulation were absent in MFB rats. The normal ACTH and CS responses to audiogenic stress were slightly delayed and attenuated, respectively, in the operated group, whereas the responses of both hormones to exposure to elevated environmental temperature were partially blocked in lesioned, as compared to intact, animals. These results demonstrate that the MFB is involved in mediating the ACTH, as well as the CS secretory responses to acute stress exposure. More specifically, the role of the MFB, vis-a vis the hypothalamo-hypophyseal-adrenal axis, appears to be in the transmission of sensory input from rostral brain areas posteriorly. PMID- 6258759 TI - [In vitro effects of glycolytic substrates and some nucleotides (ATP, ADP, AMP, cyclic AMP) on the motility of spermatozoids of human sperm, asthenospermic or normal]. AB - The effects of several drugs upon normal and asthenospermic human sperms were tested: cyclic AMP significantly and constantly increased the rate of motile spermatozoa in most samples having an initial motility rate between 20 and 60%. ATP kept up high the motility rate, particularly in sperm displaying the highest initial motility. Other drugs (glycolytic substrates, pyruvate, ADP, AMP, caffeine had inconstant effects upon a few sperms. None drug was efficient upon sperms with initial motility rate lower than 20%; this was probably due to important lesions of the locomotor apparatus of the spermatozoa, as shown by electron microscopy investigations. PMID- 6258760 TI - Thermal decomposition of human tooth enamel. AB - Further insight into human tooth enamel, dense fraction (TE), has been obtained by following the change and loss of CO3(2-), OH-, structurally incorporated H2O, Cl-, and, indirectly, HPO4(2-) after TE had been heated in N2 or vacuum in the range 25-1000 degrees C. Quantitative infrared spectroscopic, lattice parameter, and thermogravimetric measures were used. Loss of the CO3(2-) components begins at much lower temperature (e.g., 100 degrees C) than previously recognized, which has implications for treatments in vitro and possibly in vivo. CO3(2-) in B sites is lost continuously from the outset; the amount in A sites first decreases and then increases above 200 degrees to a maximum at approximately 800 degrees C (greater than 10% of the possible A sites filled), where it is responsible for an increase in a lattice parameter. A substantial fraction of the CO3(2-) in B sites moves to A sites before being evolved, apparently via a CO2 intermediary. This implies an interconnectedness of the A and B sites which may be significant in vivo. No loss of Cl- was observed at temperatures below 700-800 degrees C. Structural OH- content increases approximately 70% to a maximum near 400 degrees C. Structurally incorporated water is lost continuously up to approximately 800 degrees C with a sharp loss at 250-300 degrees C. The "sudden" a lattice parameter contraction, approximately 0.014 A, occurs at a kinetics-dependent temperature in the 250-300 degrees C range and is accompanied by reordering and the "sharp" loss of approximately 1/3 of the structurally incorporated H2O. The hypothesis that structurally incorporated H2O is the principal cause of the enlargement of the a lattice parameter of TE compared to hydroxyapatite (9.44 vs 9.42 A) is thus allowed by these experimental results. PMID- 6258761 TI - Differential diagnosis of hypoparathyroid disorders during childhood. AB - Changes in the plasma and urinary adenosine 3', 5' monophosphate (cyclic AMP) levels on infusion of parathyroid hormone were studied in 10 normal children, 5 children with idiopathic hypoparathyroidism, and 3 children with pseudohypoparathyroidism. In normal children the plasma concentration of cyclic AMP ranges from 18.0 to 68.0 pmoles/ml under basal conditions, and increases to a peak of about 10-fold the basal level 5 min after infusion of parathyroid hormone. Infusion of parathyroid hormone caused no increase in plasma cyclic AMP in patients with pseudohypoparathyroidism but about 18-fold increase in those with idiopathic hypoparathyroidism. The measurement of plasma cyclic AMP before and 5 min after infusion of parathyroid hormone is concluded to be a single and effective method for differential diagnosis of hypoparathyroid disorders. PMID- 6258763 TI - Cardiac alpha adrenoceptors. PMID- 6258762 TI - Histological observations on the failure of rachitic rat bones to respond to 1,25/OH)2D3. AB - Rachitic rats, maintained on diets with low or normal P contents, were given daily intraperitoneal doses of 1,25(OH)2D3 or 25OHD3 at levels of 100 or 200 ng. Plasma chemistry was measured and the ash content and histological appearance of the bones investigated. Using labeled material it was shown that the dosing levels of 1,25(OH)2D3 employed ensured a higher than normal plasma concentration of that metabolite over the period between doses. 1,25(OH)2D3 was not effective as 25OHD3 in raising bone ash or reducing the amount of osteoid. The difference between the effects of the metabolites was evident at both dietary P levels, but more marked at the higher P level. In contrast, the metabolites reduced the width of the epiphyseal plate to an approximately similar degree, and this is possibly the reason why there are discrepancies between previous reports of the effectiveness of 1,25(OH)2D3 compared with 25OHD3 or vitamin D3. Dosing with 1,25(OH)2D3 failed to maintain a constant plasma Pi value over the period between doses in animals fed the low P diet. PMID- 6258764 TI - beta-adrenergic responsiveness of rats treated chronically with isoproterenol. AB - The effect of chronic administration of isoproterenol on isoproterenol-induced thirst and isoproterenol-induced changes in heart rate and selected organ weights of male rats was studied. Administration of 25 micrograms isoproterenol/kg, s.c., in saline daily for 10 days was accompanied by a significant attenuation of the characteristic increase in water intake following a challenging dose of isoproterenol (25 micrograms/kg, s.c.) on the 11th day. Administration of 25 micrograms isoproterenol/kg, s.c., every 2nd, 3rd or 4th day for 10 days was without significant effect on water intake following isoproterenol (25 micrograms/kg, s.c.) on the 11th day. Administration of 25 micrograms isoproterenol/kg, s.c., every day for 10 days led to a slight increase in cardiac responsiveness to a challenging dose of isoproterenol (25 micrograms/kg) on the 11th day. Chronic treatment with this low dose of isoproterenol for 10 days was also accompanied by a significant increase in the ratio of heart weight to body weight but no significant changes in the ratio of kidney, adrenal, thyroid, spleen, or interscapular brown fat to body weight. Thus, daily administration of the beta-adrenergic agonist isoproterenol for 10 days can alter beta-adrenergic responsiveness in the rat with beta 1 (heart rate) and beta 2 (thirst) mediated responses showing opposite effects. In addition, the results suggest that tests of beta-adrenergic responsiveness must be assessed in terms of the frequency of administration of the agonist. PMID- 6258765 TI - Effects of barium on gastric microsomal K+-stimulated para-nitrophenyl phosphatase activity. AB - Ba2+ at low concentrations (1 mM or lower) stimulates the basal and K+-stimulated para-nitrophenyl phosphatase activity associated with the purified microsomal fractions from the oxyntic cells of bullfrog gastric mucosa. However, at higher concentrations Ba2+ acts as a competitive inhibitor of the K+-stimulated phosphatase. Ba2+ alone, in absence of any Mg2+, cannot maintain the enzyme activity; hence Ba2+ can only influence or modulate the Mg2+-dependent phosphatase. The effects are unique for Ba2+ because all other divalent cations such as Ca2+ and Zn2+ act as inhibitors of this enzyme under similar conditions. The data offer a possible biochemical basis for the known pharmacological effects of Ba2+ in gastric acid secretion. PMID- 6258766 TI - Smooth muscle membrane vesicle orientation: a study on intactness and sidedness of rat myometrium plasma membrane vesicles. AB - Plasma membrane vesicles of rat myometrium were prepared in media containing 240 mM sucrose. The vesicles were exposed to isotonic, hypertonic, and hypotonic sucrose concentrations, fixed, sectioned, and studied using the electron microscope. The vesicles fixed in isotonic media were circular in appearance. Vesicles fixed in hypertonic media were distorted and showed a reduced volume to surface ratio consistent with the hypothesis that greater than 80% of the vesicles were osmotically active to sucrose. Cationized ferritin binding studies and Ca binding and release studies were also consistent with this finding. Exposure to hypotonic media also yielded membranes with distorted profiles indicating that they had been ruptured. [3H]Sucrose trapping experiments revealed that the vesicles had an internal volume of 1.20-1.44 mL/g protein. Hypotonic shock treatment reduced this intravesicular volume to 0.20-0.28 mL/g protein. The hypotonic shock treatment also led to enhanced galactose oxidase catalyzed Na3B3H4 labelling of the membranes and to increased K+-activated ouabain sensitive p-nitrophenyl phosphatase activity. The enhancement was the same (55 +/ 10%) in the various membrane preparations for both the parameters. The data are interpreted to conclude that the rat myometrium plasma membrane vesicles consisted of 20% broken vesicles and equal proportions of intact vesicles of inside-out and rightside-out orientations. PMID- 6258767 TI - Effective functioning of chronic psychiatric patients in aftercare settings. AB - The purpose of this study was to determine personality and environmental characteristics as they relate to effective functioning of chronic psychiatric patients in aftercare settings in North Western Ontario. The guiding assumption was that indices of health are better predictors of effective functioning than the absence of pathology. PMID- 6258768 TI - Cell cycle-specific enhancement of type C virus activation by sodium n-butyrate. AB - The effect of sodium n-butyrate on chemical induction of xenotropic virus from synchronized Kirsten sarcoma virus-transformed BALB mouse cells was examined. When added during the last part of the G1 phase, n-butyrate produced a large increase in cycloheximide induction during S phase. Under similar conditions, activation by 5-iododeoxyuridine was inhibited. When added with cycloheximide during the S phase, n-butyrate inhibited activation of virus. Studies with synchronized cultures showed that n-butyrate delayed the onset of DNA synthesis, characteristic of the S phase, and inhibited histone deacetylation in log-phase cells. The effects produced by n-butyrate could, therefore, be the result of lengthening the G1 phase of the cell cycle or a modification of histones affecting transcription during virus activation. PMID- 6258769 TI - Elevated plasma and urinary guanosine 3':5'-monophosphate and increased production rate in patients with neoplastic diseases. AB - The plasma and 24-hr urinary levels of cyclic adenosine 3':5'-monophosphate and of cyclic guanosine 3':5'-monophosphate (cGMP) were determined for 19 healthy normal patients, 54 patients with six types of nonneoplastic diseases (cholelithiasis, peptic ulcer, coronary heart disease, hypertension, regional ileitis, and cirrhosis), and 54 patients with five types of neoplastic disease (cancers of the lung, colon, and breast, acute myelocyte leukemia, and Hodgkin's disease). The cyclic adenosine 3':5'-monophosphate levels of urine and plasma in normal subjects, in noncancer subjects, and in cancer subjects did not differ significantly. The cGMP levels in the noncancer group were similarly unchanged from those in the normal group. However, mean cGMP levels in the urine and plasma of patients with neoplastic diseases were, respectively, 2- and 3-fold greater than the normal values (p less than 0.005 for urine and p less than 0.05 for plasma). Pharmacokinetic studies with [3H]cGMP in nine healthy controls and 15 patients with neoplasia showed that the mean production rate of this nucleotide in patients with metastatic cancer was elevated when compared to normal patients, but many values fell within the normal range. In acute leukemia, the production rate was seven times normal, with four of five patients having values clearly outside the normal range. The plasma clearance rate in patients with neoplasia was not decreased when compared to that in normal patients. It is proposed that an increased production rate, rather than any change in plasma clearance, accounts for the increased levels of cGMP in the plasma and urine of some patients with neoplastic disease. PMID- 6258770 TI - Induction of leukemia-associated inhibitory activity and bone marrow granulocyte macrophage progenitor cell alterations during infection with Abelson virus. AB - Neonatal and adult BALB/c mice were investigated in a longitudinal study for the acquisition of leukemia-associated inhibitory activity (LIA) interactions after inoculation with Abelson virus in vivo. Within 2 to 4 days after virus infection, the granulocyte-macrophage colony-forming cells from the bone marrow and spleen of the infected mice became insensitive to inhibition by LIA, even though colony morphology appeared normal. Shortly after, or simultaneously with, the detection of the colony-forming cell resistance phenomenon, LIA was found in bone marrow, spleen, and thymus cells. The abnormal interactions appeared to be related to induction of lymphoma in BALB/c neonates and to a lymphoproliferative disease in adult BALB/c mice. In contrast, normal cellular interactions were noted in adult C57BL/6 mice which were not susceptible to the Abelson disease after virus inoculation and in untreated neonatal and adult BALB/c and adult C57BL/6 mice. Their colony-forming cells were sensitive to inhibition by LIA, and no LIA was detected in their bone marrow, spleen, and thymus cells. The abnormal cellular interactions are similar to those noted in human leukemia, lymphoma, and "preleukemia." This suggests that Abelson virus-infected mice can serve as a model for the study of LIA interactions. PMID- 6258771 TI - Human cell-mediated benzo(a)pyrene cytotoxicity and mutagenicity in human diploid fibroblasts. AB - A human epithelial cell-mediated cytotoxicity and mutagenicity assay system for benzo(a)pyrene [B(a)P] has been developed with human fibroblasts as the target cells. Lethally X-irradiated human kidney carcinoma-derived epithelial cells, which had constant levels of B(a)P-metabolizing activity, were cocultivated with target human skin fibroblasts (XP12BE), which lack excision repair capability for B(a)P-DNA adducts. The optimal conditions determined for the cell-mediated cytotoxicity assay were a 48-hr exposure to B(a)P concentrations ranging from 0.1 to 1 microM at a metabolizing cell:target cell ratio of at least 1:1. Under these conditions, the frequency of mutations to 6-thioguanine resistance induced in the target XP12BE cells by B(a)P as well as the binding of tritium-labeled B(a)P to DNA was also shown to be concentration dependent. High-pressure liquid chromatography analysis of enzymatically degraded B(a)P-DNA adducts revealed two peaks: a major peak (82%) which cochromatographed with the guanosine adduct standard synthesized from anti-isomeric-7,8-dihydrodiol-9,10-epoxide of B(a)P; and a minor peak (18%) which cochromatographed with the guanosine adduct-standard synthesized from syn-isomeric-7,8-diol-9,10-epoxide of B(a)P. Human liver carcinoma- and lung carcinoma-derived cell lines, capable of metabolizing B(a)P, proved equal to or better than the kidney carcinoma-derived cell line in producing cytotoxic B(a)P metabolites in the cell-mediated cytotoxicity assay with target XP12BE cells. PMID- 6258772 TI - Regulation of cyclic adenosine 3':5'-monophosphate-binding protein in N-18 mouse neuroblastoma cells. AB - The regulation of cyclic adenosine 3':5'-monophosphate (cAMP)-binding protein in N-18 neuroblastoma cells in tissue culture was studied by the covalent incorporation of 8-azido-cyclic adenosine 3':5'-[32P]monophosphate, together with the techniques of sodium dodecyl sulfate:polyacrylamide gel electrophoresis and autoradiography. Greater than 95% of the total cAMP binding activity of N-18 neuroblastoma cells was identified as being regulatory subunits of the type I (RI) and type II (RII) species, with RI being the predominant form of the two (RI:RII = 3:1). The specific activity of RI but not of RII increased 3-fold when cells were grown in medium containing 1% rather than 10% fetal calf serum. Under the same conditions, the specific activity of acetylcholinesterase increased 3- to 5-fold. The increase in RI was inversely related to the serum concentration in the medium and was specific for cells at the stationary phase of growth. An increase in intracellular cAMP, concomitant with the increase in RI, was also observed. Morphological examination of stationary-phase neuroblastoma cells maintained in medium containing 1% fetal calf serum suggested the presence of a high proportion of highly-differentiated cells. It is proposed that the regulatory control of RI cAMP-binding protein by serum may involve modulation of intracellular cAMP and that the expression RI may be used as a biochemical index of differentiation in mouse neuroblastoma cells. PMID- 6258773 TI - Cellular binding proteins for vitamin A in human carcinomas and in normal tissues. AB - Blinded analyses of the concentrations of binding proteins for retinol and retinoic acid (CRABP) in homogenates of cancer and normal tissue aliquots obtained from human cervix, endometrium, ovary, breast, and lung were carried out by the sucrose gradient ultracentrifugation technique. In carcinomas of the cervix and endometrium, CRABP mean values of 50.4 and 123.2 pmol/g tissue, respectively were detected. Such concentrations represent a 3- and 4-fold increase over the mean values of CRABP in the normal cervix (16.9 pmol/g) and normal endometrium (30.8 pmol/g), respectively. In carcinomas of the ovary, the mean CRABP level was 128.6 pmol/g compared to the maximal mean value of less than or equal to 0.46 pmol/g in the normal ovary. Elevated levels of CRABP were also found in breast and lung carcinomas compared to the amounts detected in the same patient in normal tissue aliquots of the same organ. The differences between CRABP concentrations in cervical, endometrial, ovarian, and breast carcinomas and those in normal tissue are statistically significant. In contrast, cellular retinol-binding protein concentrations were reduced in the endometrial, ovarian, breast, and lung carcinomas compared to normal tissues. There were no significant differences between the log-mean concentrations of cellular retinol-binding proteins in the cytosols from tissue aliquots of carcinoma of the cervix and those in the cytosols from tissue aliquots of normal cervix. PMID- 6258774 TI - Development and characterization of mouse hyperplastic mammary outgrowth lines from BALB/cfC3H hyperplastic alveolar nodules. AB - Five hyperplastic outgrowth lines were developed by serial transplantation of hyperplastic alveolar nodules from BALB/cfC3H mice into BALB/c hosts. The lines were used to study the biology, morphology, and virology of premalignant tissue originating in mouse mammary tumor virus (MuMTV)-positive animals. The five lines differed with respect to tumor potential and growth characteristics, corroborating the previous evidence that MuMTV-positive hyperplastic alveolar nodules are biologically heterogeneous. Subgross and microscopic examination of outgrowths and tumors revealed that each line had unique morphological characteristics. The presence of atypical lobules within the hyperplastic outgrowth appeared to be correlated with tumor risk, and a morphological continuum of atypical lesions ending in overt cancer was suggested. Viral expression was detected by nucleic acid hybridization and immunoperoxidase staining for MuMTV structural antigens. While the MuMTV RNA in certain tissues appeared to vary qualitatively with tumor potential of the outgrowth line, no correlation between viral antigens detected by immunoperoxidase staining and tumor potential was observed. PMID- 6258775 TI - Phase I clinical and pharmacokinetic study of 4'-(9-acridinylamino)-methanesulfon m-anisidide in children with cancer. AB - Forty-one pediatric patients with advanced cancer (24 with acute leukemia and 17 with diverse solid tumors) received 74 courses of therapy with a new chemotherapeutic agent, 4'-(9-acridinylamino)methanesulfon-m-anisidide (AMSA: NSC 249992). Treatments were given by slow i.v. injection daily for five days every two to three weeks. In patients with leukemia: (a) dosages were escalated from 1.3 to 150 mg/sq m/day; (b) toxicity in the form of stomatitis, vomiting, and phlebitis occurred at dosage levels of 125 to 150 mg/sq m/day; and (c) oncolytic effects were observed in 13 of 24 patients. In patients with solid tumors: (a) dosages were escalated from 5 to 50 mg/sq m/day; (b) toxicity (stomatitis, myelosuppression, and phlebitis) occurred at the dosage level of 50 mg/sq m/day; and (c) no oncolytic responses were noted. Serum concentrations of total and free AMSA were assayed by a fluorescence technique and declined in a biphasic manner with free AMSA declining more rapidly than total AMSA. Dosages of greater than 100 mg/sq m/day were required to maintain serum concentrations of total and free AMSA greater than 0.2 microM for the entire five-day schedule. The results suggest that maximum tolerated dosages of AMSA may differ in children with leukemia and solid tumors; however, hematopoietic toxicity could not be fully evaluated in the patients with leukemia. AMSA has clear antileukemic activity that warrants future Phase II trials. PMID- 6258777 TI - Clonal heterogeneity of small-cell anaplastic carcinoma of the lung demonstrated by flow-cytometric DNA analysis. AB - Flow-cytometric DNA analysis yields information on ploidy and proliferative characteristics of a cell population. The analysis was implemented on small-cell anaplastic carcinoma of the lung using a rapid detergent technique for the preparation of fine-needle aspirates for DNA determination and a newly developed procedure for storing aspirates at -80 degrees. Thirty-eight different metastases in 30 consecutive patients with small-cell anaplastic carcinoma of the lung were examined with a total of 273 fine-needle aspirations. The results on ploidy are reported in this paper. The degree of contamination of the aspirates with normal cells was determined by differential counts. The ratio of the peak channel numbers for the G1 phase of the tumor cells to that of the diploid standard (DNA index) was calculated and used for ploidy identification. Twenty-nine patients were evaluable with respect to DNA index determination. The coefficient of variation of the DNA index determinations was estimated as 0.039. In 23 (79%) patients, only one cell line could be detected. Evidence of the presence of 2 tumor cell clones with different ploidy was obtained in the remaining 6 (21%) patients. Of the 35 malignant clones thus demonstrated, 26 (74%) were significantly different from diploid (p less than or equal to 0.01). Four (11%) were hypodiploid, 3 (9%) were hypotriploid, and 19 (54%) were hypo- or near tetraploid. Clonal heterogeneity in the tumors of 21% of the patients is a conservative estimate. Assessment of the detection limit set by the methodology used and the restricted number of samples studied in each patient indicate that the true occurrence of clonal heterogeneity in small-cell carcinoma of the lung may be much higher. PMID- 6258776 TI - Quantitative estimation of cellular retinoic acid-binding protein activity in normal, dysplastic, and neoplastic human breast tissue. AB - A technique for reproduction and quantitative determination of human cellular retinoic acid-binding protein (CRABP) activity in breast tissue specimens is described. A multiphasic polyacrylamide disc gel electrophoresis system (operative at pH 10.2) was adapted for this purpose. This technique allows, after incubation with tritiated retinoic acid (RA) overnight, the separation of the specific CRABP activity from the nonspecific serum-originated binding activity and from the free RA. Previous purification of the tissue cytosols is therefore not necessary. The same assay method was also used for the determination of the molecular weight (Ferguson plot, m.w. 13,000) and the dissociation constant Kd (2.5 x 10(-7) M) of mammary CRABP. The activity in tissue cytosol, stored at -70 degrees, was found to be stable for at least 3 months. Results from 88 breast tissue specimens of different pathological degree are presented. CRABP activity was found in all tissue categories with progressively increasing amounts from normal tissue to breast cancer. The activity in the cancer tissues (14.85 +/- 12.05 pmol RA bound per mg soluble protein: N = 27) was significantly different (p less than 0.001) from the activity determined in tissue with simple dysplasia without epithelial proliferation [4.3 +/- 2.2 (S.D.) pmol RA bound per mg protein; N = 30]. It is possible that in the cases where high amounts of CRABP activity are found in dysplastic and preneoplastic tissue, a high risk for breast cancer development exists. Therefore, CRABP is tentatively proposed as a dedifferentiation and/or proliferation marker. PMID- 6258779 TI - Induction of Epstein-Barr virus antigens in human lymphoblastoid P3HR-1 cells with culture fluid of Fusobacterium nucleatum. AB - Epstein-Barr virus-associated early antigen and viral capsid antigen were efficiently induced in human lymphoblastoid P3HR-1 cells with culture fluid of Fusobacterium nucleatum, a member of the indigenous microbial flora of the human host. This finding may suggest a new approach to assess the possible role of the "cofactor(s)" in the etiology of Epstein-Barr virus-related diseases. PMID- 6258780 TI - Regulation of endogenous murine leukemia virus-related nuclear and cytoplasmic RNA complexity in C57BL/6J mice of increasing age. AB - The nucleotide sequence complexity of murine leukemia virus *MuLV)-related RNA has been measured by RNA-complementary DNA hybridization analysis in nuclear and cytoplasmic RNA isolated from liver and brain of low-leukemia-strain C57BL/6J mice of different ages. In these two tissues, an approximate 1.5- to 2-fold increase in the complexity of steadystate nuclear MuLV-related RNA sequences was observed as a function of age. Maximum complexity was observed with nuclear RNA extracts from old mice and corresponded to roughly 70 to 75% of the total MuLV genome. In contrast to the age-related increase in complexity of nuclear MuLV genome was detected in liver and brain steady-state cytoplasmic RNA, irrespective of animal age. These data suggest that control mechanisms regulating the transcription and/or stabilization of nuclear RNA transcripts of endogenous mouse MuLV-related genomes become less stringent with animal age even in low-tumor mouse strains. The data also support the existence of independent posttranscriptional mechanisms which prevent accumulation of these MuLV-related transcripts in steady-state cytoplasmic RNA and which do not seem to be as subject to the relaxation of stringency as a function of age. PMID- 6258778 TI - Differential induction of squamous cell carcinomas and adenocarcinomas in mouse lung by intratracheal instillation of benzo(a)pyrene and charcoal powder. AB - Differential induction of squamous cell carcinomas, adenomas, and adenocarcinomas was observed in the lungs of male C57BL/6 and C3H/He mice after repeated intratracheal instillation of benzo(a)pyrene (BP) and charcoal powder suspended in 0.9% NaCl solution. when a high dose of BP (1.0 mg BP and 0.5 mg charcoal powder) was instilled intratracheally once a week for 8 weeks or when a low dose of BP (0.5 mg BP and 0.5 mg charcoal powder) was instilled once a week for 16 weeks, squamous cell carcinomas were induced in high incidence (77 to 87%) in the early period of observation, whereas pulmonary adenomas and adenocarcinomas were induced in low incidence (0. to 48%) in the late period of observation in both strains of mice. On the other hand, when a low dose of BP was instilled intratracheally once a week for 8 weeks, pulmonary adenomas and adenocarcinomas were induced in high incidence (76 to 91%), but squamous cell carcinomas were induced in low incidence (9 to 26%). These results show that a larger quantity of BP instilled intratracheally was needed for induction of squamous cell carcinomas than for induction of adenomas and adenocarcinomas in the lung of mice. Thus, when the carcinogen is administered to a single organ of a single mouse strain by the same route, different amounts of carcinogen have different effects on the incidences of various histological types of tumors. PMID- 6258781 TI - Detection of infectious centers in C57BL/Ka lymphoid cell populations infected in vitro by the radiation leukemia virus. AB - The cocultivation of nonproducer lymphoma cells derived from a radiation-induced lymphoma of the C57BL/Ka mouse with cultures of lymphoid cell populations from the thymus, spleen, and marrow of the same strain 48 hr after their infection by the C57BL/Ka leukemia viruses permits the detection of infectious centers in these cultures. A quantitative assay is described which allows the estimation in lymphoid cell subpopulations of the numbers of target cells susceptible to productive infection by the thymotropic and leukemogenic viruses of C57BL/Ka mice in vitro. This assay should greatly facilitate the identification and characterization of such target cells. PMID- 6258783 TI - Absence of macrophage involvement in the passive serum therapy of Friend leukemia virus-induced disease. AB - The possible involvement of host macrophages in the passive serum therapy of Friend leukemia virus (FLV)-induced disease has been examined with the use of agents inhibiting normal macrophage functions, including silica and a tumor produced macrophage chemotaxis inhibitor. Under conditions in which macrophage chemotaxis inhibitor. Under conditions in which macrophage functions are at least transiently abrogated by these agents, no effect was seen on the anti-fLV protection afforded by the passive administration of chimpanzee anti-FLV antiserum to infected DBA/2 mice, as monitored by the development of virus induced splenomegaly and the level of infectious virus. The macrophage inhibitors also did not influence the appearance of the host antiviral humoral immune response which normally accompanies serum protection. These results suggest that the normal functioning of host macrophages do not play a central role in the passive serum therapy protective mechanism leading to resistance to FLV infection. PMID- 6258782 TI - Secretion of proteinases from malignant and nonmalignant human breast tissue. AB - Both malignant (adenocarcinomas) and nonmalignant (fibroadenomas and normal tissue) human breast tissues were maintained in organ culture for up to 10 days to study the secretion of lysosomal and neutral proteinases. Little difference was observed between the different tissue groups in the release of the lysosomal proteinase cathepsin D into the culture medium. Similar results were obtained when media were tested for plasminogen activator activity. The secretion of collagenolytic activity was investigated with fibroadenoma and adenocarcinoma explants and found to be very low for both tissue groups. The average accumulation of collagenase activity during a 2-day period was 0.002 units/microgram DNA for adenocarcinomas and 0.008 units/microgram DNA for fibroadenomas. The only proteinase that was secreted in substantially higher amounts from explants of malignant tissue was a cathepsin B-like thiol proteinase. Media from adenocarcinoma explants (n = 38) contained on the average 11 times more activity than did media from fibroadenoma (n = 20) and normal tissue explants (n = 8). Metastases of mammary adenocarcinomas (n = 7) secreted the thiol proteinase at about one third of the rate of primary tumors. The secretion of this enzyme is dependent upon protein synthesis as its release was completely inhibited 24 hr after the addition of cycloheximide. In some cases, it was also observed that the presence of sheep serum in the tissue culture medium reduced the accumulation of activity. PMID- 6258784 TI - Ornithine decarboxylase induction during B1 progression of normal and Rous sarcoma virus-transformed cells. AB - Ornithine decarboxylase (ODC) induction during G1 phase of the cell cycle was compared in Rat-1 fibroblasts and in Rat-1 fibroblasts transformed by the B77 wild-type Rous sarcoma virus (RSV) and by the thermosensitive mutant LA24/RSV. In Rat-1 cells, maximal enzyme activity detectable at mid G1 declined to basal levels by G1-S. The ODC increase was inhibited by actinomycin D and cycloheximide and was dependent on the addition of serum growth factors. Rat-1 (B77 wild-type RSV) cells expressed a greater amount of enzyme activity after serum stimulation, and the maximal level of enzyme activity detectable at mid G1 declined only 50% so that elevated ODC was maintained during G1-S transition. The enzyme increase in the transformed cell line was not dependent on serum growth factors. Fresh medium addition alone induced enzyme activity. Induction in the presence or absence of serum required both RNA and protein synthesis. ODC induction in the transformed cells was less sensitive to repression by exogenous putrescine addition. A 100-fold greater concentration of the diamine was required to produce comparable inhibition in the Rat-1 (B77 wild-type RSV) as compared to the Rat-1 cell. These alterations in the characteristics of ODC expression were found to be a consequence of the transforming function of RSV in the Rat-1 cell line transformed by the thermosensitive viral mutant LA24. In response to serum stimulation at the nonpermissive temperature (39 degrees), Rat-1 (thermosensitive mutant LA24/RSV) cells displayed a discrete G1-phase ODC induction while those cells maintained at the permissive temperature (35 degrees) exhibited a greater and prolonged ODC induction in G1 and S phases. A shift from 39 to 35 degrees in the absence of any medium or serum addition stimulated the induction of ODC expressed in a transformed phenotypic manner. Greater concentrations of exogenous putrescine were required to repress the induction of ODC at 35 than at 39 degrees. Alterations in ODC regulation, therefore, may be inherent to the neoplastic phenotypic change. PMID- 6258785 TI - Depletion of total hemolytic complement in sera from hamsters bearing herpes simplex type 2-induced tumors. AB - Total hemolytic complement (CH50) levels were compared in sera from normal hamsters and hamsters bearing tumors derived from herpes simplex virus type 2 transformed cells CH50 in normal sera ranged from 160 to 212 while CH50 in tumor bearer sera ranged from 82 to 146. Preincubation of tumor bearer sera with cell surface proteins (CSP) from homologous herpes simplex virus type 2-derived tumor cells resulted in a 66% depletion of CH50 whereas preincubation with heterologous herpes simplex virus type 1-derived tumor CSP resulted in a decrease of 26%. The depletion of CH50 appeared to occur via the classic complement pathway. Similar results were seen using CSP from herpes simplex virus-infected cells although overall depletion of CH50 was considerably less than that seen using tumor cell material. Using the complement subcomponent 1q(C1q)-binding test, tumor bearer sera and tumor bearer sera preincubated with homologous CSP were shown to contain increased levels of immune complexes not present in normal serum. These results indicate that the observed depletion of complement activity in sera from tumor bearing hamsters could be the result of complement pathway activation by antigen antibody complexes. PMID- 6258786 TI - Induction of two transformation-sensitive membrane polypeptides in normal rat kidney cells by iron deprivation. AB - Rapid depletion of iron from the growth medium induces the synthesis of two membrane proteins with a subunit molecular weight of 160,000 (160K) and 130,000 (130K) in cultured normal rat kidney cells. When iron is maintained at normal levels in the growth medium of normal rat kidney cells, the synthesis of the 160K and 130K proteins is suppressed. We found that 160K and 130K are the underglycosylated forms of two membrane glycoproteins, 163K and 132K, respectively. We estimated the apparent turnover rate of the underglycosylated proteins and showed that it is slower than that of the fully glycosylated forms. Upon removal of iron from the growth medium pf simian virus 40-transformed normal rat kidney cells and Kirsten sarcoma virus-transformed normal rat kidney cells, 160K and 130K did not increase to levels comparable to those of normal rat kidney cells. Two different clones of simian virus 40-transformed normal rat kidney cells subjected to iron deprivation showed greatly reduced levels of 160K, and in one of these clones, 130K was absent. Kirsten sarcoma virus-transformed normal rat kidney cells also showed a defective response to iron deprivation manifested by reduced levels of both 160K and 130K. Additional studies indicate that these glycoproteins are membrane-associated procollagen molecules. The alteration in the coordinated induction of 160K and 130K in transformed cells suggests that these membrane-associated proteins may have an important role in transformation. PMID- 6258787 TI - Natural feline leukemia virus infection and the immune response of cats of different ages. AB - Forty-two kittens and 28 adult cats were placed as tracers in leukemia cluster environments in contact with resident cats, 30% of which were persistently infected with feline leukemia virus (FeLV). After 7 months exposure, FeLV viremia had been detected in 71% of the tracer kittens, although only 55% of these remained persistently infected; in the same period, 11% of tracer adults became infected, but by 2 years the figure reached 43%. Mean latent periods before detection of viremia were 3.4 +/- 1.8 (S.D.) and 13.0 +/- 5.9 months for kittens and adults, respectively. First detection of FeLV infection was accompanied by a sharp although transient drop in peripheral white blood cell numbers, and infection onset triggered the humoral immune response which was comprised of separate antibodies with virus-neutralizing and tumor lysis activities. High titers of virus-neutralizing antibody appeared in transiently viremic cats immediately following elimination of viremia; this antibody was rarely detected in cats that remained persistently viremic. Lytic complement-dependent antibody to feline oncornavirus-associated cell membrane antigen appeared in most cats 1 to 2 weeks after FeLV infection was first detected, and subsequently high titers of this antibody remained in both transiently and persistently infected cats. If the rate of FeLV infection was summarized by using viremia and/or antibody appearance, then 95% of the kittens became infected within 1 year and 61% of the adults within 2 years. Adult cats are, therefore, susceptible to FeLV infection following long-term natural exposure, and their apparent resistance cannot be attributed to a protective humoral immune response that developed immediately after exposure commenced. PMID- 6258788 TI - Alteration of murine mammary tumor metastasis and growth by cytomegalovirus infection. AB - Host resistance to the development of metastatic lesions is complex and involves both lymphocyte and macrophage functions. Studies in both humans and animals have suggested that cytomegalovirus infection may alter these components of the defense mechanism of the host. In the present study, an experimental model was developed to determine whether cytomegalovirus infection would affect host resistance to the establishment of metastatic tumor nodules in the lungs of C3H mice after i.v. inoculation of a single-cell suspension of mammary tumor cells. The number of tumor nodules in the lungs, the lungs-heart/body weight ratio, and the mean day of death were determined in control animals inoculated i.v. with 10(6) mammary tumor cells and compared with groups of animals also receiving a sublethal i.p. inoculum of murine cytomegalovirus (MCMV) (10(5) plaque-forming units) either 3 days before, on the day of, or 10 or 13 days after tumor cell inoculation. The results suggest a biphasic effect of virus infection on tumor development in the lung. A preexisting or concurrent MCMV infection suppressed tumor growth and prolonged life, while a MCMV infection later in tumorigenesis enhanced tumor growth and shortened survival. These data suggest that MCMV modulates host resistance to the development of metastatic tumor nodules and that this experimental model may be utilized to investigate further the relationship between virus-induced alterations of host defense mechanisms and tumor growth. PMID- 6258789 TI - Presence of steroid receptors in human soft tissue sarcomas of diverse histological origin. AB - The incidence of cytosol receptors for androgen, estrogen, glucocorticoid, and progesterone was determined in a series of histologically diverse soft tissue sarcomas. Receptor binding was characterized in tumor specimens from 29 adult patients (14 female, 15 male) obtained during surgery. Nineteen (66%) tumor cytosols bound at least one steroid. Seven (24%) had more than one receptor. Ten of 23 (43%) cytosols assayed for androgen binding were positive (Kd 0.97 +/- 0.23 X 10(-9) M; 60.6 +/- 25.9 fmol/mg protein), 7 of 29 (24%) for estrogen (Kd 1.00 +/- 0.19 X 10(-9) M; 33.2 +/- 10.9 fmol/mg protein), 9 of 26 (35%) bound glucocorticoid (Kd 4.22 +/- 1.77 X 10(-9) M; 231.0 +/- 155.0 fmol/mg protein), and 1 of 28 (4%) bound progesterone (Kd 0.41 X 10(-9) M; 18.7 fmol/mg protein). Density gradient analysis suggested that androgen and estrogen binding was located predominantly in the 6S and 7 to 8S regions, respectively, whereas receptor for glucocorticoid sedimented at 8S. Steroid binding was not related to patient age. Estrogen-positive (71%) and glucocorticoid-positive (78%) cytosols appeared predominantly in tumors from female patients. Receptor distribution also appeared to be correlated to tumor histogenetic origin. PMID- 6258790 TI - Extensive adenocarcinoma and large cell undifferentiated carcinoma of the lung treated with 5-FU, vincristine, and mitomycin C (FOMi). AB - Fifty-six patients with extensive (52 with TNM stage III M1 disease and four with TNM stage III M0 disease) adenocarcinoma (46 patients) and large cell undifferentiated carcinoma (ten patients) of the lung were treated with combination chemotherapy consisting of 5-FU, vincristine, and mitomycin C (FOMi). The patients had not received prior chemotherapy. The overall response rate was 41% (23 of 56 patients). Four patients achieved a complete response and 19 achieved a partial response. In 12 patients the disease was stable. Response did not vary by cell type: adenocarcinoma, 18 of 43 patients (42%); large cell carcinoma, four of ten (40%); and alveolar cell carcinoma, one of three (33%). The response varied by initial performance status. For a Karnofsky score of greater than or equal to 70%, 20 of 41 patients (49%) responded, while for a Karnofsky score of less than 70%, three of 15 patients (20%) responded (P = 0.22). Survival was improved for responding patients regardless of initial performance status. The median survival duration was 24 weeks for the entire group of patients treated with FOMi. Survival of the responders (complete response plus partial response) was significantly improved over that of patients with progressive disease (28 weeks versus 13 weeks, respectively; P = 0.002). The FOMi combination was very well-tolerated. Nausea was common, but vomiting occurred in only four of 56 patients. Thrombocytopenia, requiring a reduction in the mitomycin C dose, developed after the third treatment course in 14 patients. PMID- 6258791 TI - High-dose cisplatin with fluid and mannitol-induced diuresis in advanced lung cancer: a phase II clinical trial of the EORTC Lung Cancer Working Party (Belgium). AB - A phase II clinical trial of high-dose cisplatin (120 mg/m2 iv every 3 weeks), with fluid and mannitol-induced diuresis, was conducted in 81 patients with advanced lung cancer. Partial remissions were documented in 26% of 75 evaluable cases for a median duration of 3.5 months. Adenocarcinoma and small cell anaplastic carcinoma were more responsive than epidermoid carcinoma, with partial response rates of 35%, 30%, and 18%, respectively. The median survival of responders (8.5 months) was significantly longer than the survival of nonresponders (4 months) (P less than 0.02). Myelosuppression was mild. Renal toxicity with peak serum creatinine greater than 2.5 mg/100 ml occurred in eight patients, with one death occurring due to toxicity. Cisplatin is an active drug in advanced lung cancer. PMID- 6258792 TI - Severe skin necrosis produced by piperazinedione extravasation. PMID- 6258793 TI - Detection of herpes simplex-associated antigens and antibodies in patients with cervical carcinoma in Buenos Aires. PMID- 6258794 TI - Control of the pars intermedia of the lizard, Anolis carolinensis. V. Extravascular transfer and cellular uptake of horseradish peroxidase in the neuro intermediate lobe. AB - The distribution of the tracer substance horseradish peroxidase (HRP, Mw 40,000) in the neuro-intermediate lobe of the lizard, Anolis carolinensis, was studied at various time intervals (13 min to 24 h) after vascular injection. HRP rapidly entered the extracellular lumen of the neural lobe, but did not penetrate into the third ventricle. The tracer was found in micropinocytotic vesicles (MPVs) of ependymal cells within 13 min after injection. The number of cellular inclusions containing HRP increased during the period of observation (24h). The tracer was sparsely taken up by aminergic and peptidergic nerve terminals of the external layer. After transection of the hypophysial stalk, numerous dense, labelled droplets were found in the peptidergic terminals, and the number of labelled inclusions in ependymal cells increased. MPVs were frequently found in extensions of stellate cells of the intermediate lobe, and endocytotic vacuoles (EVs) developed especially in the perikaryon. HRP was also found in large cisternae of the secretory cells, appearing predominantly towards the perivascular septum (PVS). These cisternae were found to communicate with the extracellular lumen, probably representing a system of the extracellular space extending into the secretory cell. After transection of the hypophysial stalk, there was an increase in the number of small EVs in secretory cells of the intermediate lobe. The results are discussed in terms of MSH-release regulation and possible participation of the extracellular lumen, glial and stellate cells in the transport of regulating factors and secretory material. PMID- 6258795 TI - The effect of polymyxin B and some mast-cell constituents on mucosal mast cells in the duodenum of the rat. AB - Mucosal mast cells in the rat duodenum show no morphological signs of exocytosis of granules and do not release histamine after treatment with polymyxin B in doses large enough to cause almost complete degranulation of connective-tissue mast cells of tongue, skin, and mesentery with concomitant release of approximately 60% of the tissue histamine. Administration of polymyxin B in gradually increasing doses over a period of 5 ds resulted in a statistically significant increase in mucosal mast cells and a comparable increase in duodenal histamine content, whereas the connective-tissue mast cells in the other tissues examined became fewer in number, the remaining cells showing profound morphological changes, and tissue histamine levels, were reduced to approximately 40% of the controls. A similar increase in mucosal mast cells has been observed after treatment with another mast-cell secretagogue, compound 48/80. This suggests that the increase in mucosal mast cells may be an indirect effect of these compounds, related to their activation of other mast cells and mediated by material(s) secreted by the connective-tissue mast cells. Possible mediators such as heparin, histamine, and 5-hydroxytryptamine injected for 5 ds in doses large enough to account for the amount released from the degranulated mast cells had no effect on the morphology or numbers of mast cells in any of the tissues examined. PMID- 6258796 TI - Report of a pancreatic polypeptide-producing islet-cell tumour of the pancreas causing the watery diarrhoea, hypokalaemia, achlorhydria syndrome in a 55 year old Zimbabwean African male. PMID- 6258797 TI - Analysis of avian leukosis virus DNA and RNA in bursal tumours: viral gene expression is not required for maintenance of the tumor state. AB - Each of twelve tumors induced by either Rous-associated virus-1 or -2 (RAV-1 or RAV-2) contained a predominant population of cells with ALV proviruses integrated at common sites, consistent with a clonal origin. Seven of nine RAV-2-induced bursal tumors contained single proviruses, and all seven solitary proviruses had suffered deletions. The detailed structures of four of these proviruses show that major deletions had occurred near or at the 5' ends, spanning sequences potentially important in the production of viral RNA. One provirus also lacked most of the information coding for the replicative functions of the virus. Restriction maps suggest that these four proviruses were inserted in similar regions of the host genome. We have studied virus-specific RNA in four bursal tumors and four cell lines derived from bursal tumors. No normal viral RNA species were detectable in three tumors containing single aberrant proviruses. However, transcripts of 2.2. kb which reacted only with a hybridization probe specific for the 5' end of viral RNA were observed in one of these three tumors. Analogous species, varying in length from 1.5 to 6.0 kb, were observed in a fourth bursal tumor with multiple proviruses and in all four cell lines. (This tumor and the cell lines also contained normal species of ALV mRNA and apparently normal proviral DNA). The structures of the aberrant proviruses and the absence of normal viral RNA in some tumors indicate that expression of viral genes is not required for maintenance of the tumor phenotype. In at least some cases, the mechanism of oncogenesis may involve stimulation of transcription of flanking cellular sequences by a viral promoter. PMID- 6258799 TI - Cloned mouse mammary tumor virus DNA is biologically active in transfected mouse cells and its expression is stimulated by glucocorticoid hormones. AB - We have cloned circular unintegrated mouse mammary tumor virus (MMTV) DNA from infected rat hepatoma cells in bacteriophage lambda. Seven independent clones containing MMTV DNA of homogeneous length of 9 kb (five) or 10 kb (two) were identified. The five 9 kb clones had identical restriction maps consistent with that of 9 kb unintegrated DNA; the other two were aberrant. MMTV DNA inserts were purified, ligated and used for cotransfection of Ltk- cells together with a plasmid containing the thymidine kinase gene of herpes simplex virus. All Tk+ cell clones acquired new MMTV sequences and those transfected with the 9 kb MMTV DNA synthesized normal viral RNA and proteins. Viral gene expression was increased by the addition of dexamethasone. PMID- 6258798 TI - Avian leukosis virus-induced tumors have common proviral integration sites and synthesize discrete new RNAs: oncogenesis by promoter insertion. AB - Unlike other RNA tumor viruses, avian leukosis viruses (which cause lymphomas and occasionally other neoplasms) lack discrete "transforming genes". We have analyzed the virus-related DNA and RNA of avian leukosis virus (ALV)-induced tumors in an attempt to gain insight into the mechanism of ALV oncogenesis. Our results show that viral gene products are not required for maintenance of neoplastic transformation. Primary and metastatic tumors are clonal and thus presumably derived from a single infected cell. Most importantly, tumors from different birds have integration sites in common. Tumor cells synthesize discrete new poly(A) RNAs consisting of viral sequences covalently linked to cellular sequences. These RNA species are expressed at high levels in tumor cells. Our results suggest that in lymphoid tumors, an ALV provirus is integrated adjacent to a specific cellular gene, and the insertion of the viral promoter adjacent to this gene results in its enhanced expression, leading to neoplasia. These results have potentially important implications for the mechanism of non-viral carcinogenesis. PMID- 6258800 TI - Polyoma large T antigen regulates the integration of viral DNA sequences into the genome of transformed cells. PMID- 6258801 TI - Isolation of actively transcribed nucleosomes using immobilized HMG 14 and 17 and an analysis of alpha-globin chromatin. AB - Taking advantage of the known specificity of interaction of HMG 14 and 17 with actively transcribed chromatin, we have covalently cross-linked these proteins to agarose and used this HMG 14-17 column to purify active nucleosomes. The column has been used to map the DNA regions surrounding the chicken alpha-globin genes for their capacity to bind HMG 14-17. The results show that at a crude level the HMG binding region correlates with the major stable primary transcript and the region of DNAase I sensitivity. At a finer level of analysis, however, the correspondence between DNAase I sensitivity and HMG binding is preserved, yet this chromosomal domain is shown to extend about 1 kb beyond the known primary transcript for the two chicken alpha genes. Why HMG 14 and 17 bind specifically to active nucleosomes is still not known. Our experiments suggest that at least one additional chemical difference distinguishes them. This difference is not reflected in the DNA:protein ratio; in the electrophoretic mobility of the particles or associated DNA; in the inner histone stoichiometry; in a marked degree of histone modification as assayed on Triton-urea gels; or in the presence of nonhistone proteins. Active nucleosomes can be dissociated and reconstituted and their ability to bind to HMG 14-17 restored. The ability to reconstitute binding should make it possible to determine whether the specificity for the interaction resides in the protein or the DNA. PMID- 6258802 TI - Chromatin structure of the histone genes of D. melanogaster. AB - We have examined the chromatin structure of the histone gene repeat of D. melanogaster using an indirect end-labeling technique. Our results show that each DNA segment of the repeat is packaged into a precisely defined and characteristic structure, as follows: the nontranscribed spacers display a "normal" chromatin arrangement, with each nucleosome precisely positioned on the underlying DNA sequence; the 5' ends of all five histone genes are in an exposed configuration, highly sensitive to both micrococcal nuclease and DNAase I; and the genes have an "altered" chromatin structure, as indicated by the weak and irregularly spaced nuclease cuts. This well-defined chromatin arrangement is established early in development and is stably maintained throughout the remainder of the D. melanogaster life cycle. PMID- 6258803 TI - Fluorescence photobleaching recovery measurements reveal differences in envelopment of Sindbis and vesicular stomatitis viruses. AB - Fluorescence photobleaching recovery (FPR) measurements of virus glycoproteins on the surfaces of cells infected with vesicular stomatitis virus (VSV) and Sindbis virus showed that the VSV glycoprotein (G) remained mobile throughout the infectious cycle, whereas Sindbis virus glycoproteins (E1, E2) were partially mobile early after infection and immobile at later times when greater amounts of these proteins were on the cell surface. A highly mobile fraction of Sindbis virus glycoproteins was detected throughout the replication cycle of a temperature-sensitive mutant unable to form virus particles. This immobilization of E1 and E2 was the result of increasing surface glycoprotein concentrations and virus budding. Together with other data, which included the detection of E1 and E2 in particles as soon as these proteins were transported to the cell surface, the FPR results suggest that Sindbis virus assembly initiates on intracellular vesicles, where glycoproteins aggregate and bind nucleocapsids. In contrast, our FPR data on VSV support a model previously suggested by others, in which a small fraction of cell-surface G is immobilized into budding sites formed by interactions with virus matrix and nucleoproteins. FPR measurements also provide direct evidence for strong interactions between E1 and E2, as well as between E1 and PE2, the precursor form of E2. PMID- 6258804 TI - Localized attenuation and discontinuous synthesis during vesicular stomatitis virus transcription. AB - We have analyzed the process of partial transcription termination (attenuation), which results in nonequimolar synthesis of vesicular stomatitis virus (VSV) mRNAs during sequential transcription. Comparison of the level of transcription of defined regions of the VSV genome by DNA-RNA hybridization shows that attenuation occurs at or near the intergenic regions, rather than nonspecifically throughout the genome. Transcription decreases 29-33% across the junctions of the N-NS, NS-M and M-G genes, resulting in a cumulative effect on gene expression. This is the first example of a site-specific attenuation mechanism in a eucaryotic system. Analysis of the kinetics of transcription in vitro shows that transcription appears to be discontinuous, with significant pauses (2.5-5.7 min) occurring at or near the intergenic regions. Such pauses may occur during polyadenylation by a "slippage" mechanism at the U7 sequences present at each gene junction, or may be due to some other process, such as initiation or capping, which is slow relative to transcription. PMID- 6258805 TI - Calmodulin activates NAD kinase of sea urchin eggs: an early event of fertilization. AB - NAD kinase, one of the first enzymes activated after fertilization of sea urchin eggs, is regulated by Ca2+ and calmodulin in vitro. The evidence is the requirement for low amounts of Ca2+ (Kd for Ca2+ of 4 x 10(-7) M) and the dissociation of a heat-stable activator from the enzyme which is similar to calmodulin on the basis of radioimmunoassay, activation of bovine brain phosphodiesterase and coelectrophoresis of a major protein of the activator fraction with bovine calmodulin. Also, the calcium stimulation of the enzyme is prevented by trifluoperazine, an inhibitor of calmodulin-associated reactions. In vivo studies show that the enzyme is activated by artificial parthenogenesis regimes that increase cytosolic Ca2+, but not by ammonia activation which only partially activates eggs and bypasses the Ca2+-rise step. These in vitro and in vivo studies indicate that calmodulin is part of the linkage between the rise in Ca2+ at fertilization and the turning on of egg metabolism. PMID- 6258806 TI - Transposable elements associated with constitutive expression of yeast alcohol dehydrogenase II. AB - The yeast structural gene ADR2, coding for the glucose-repressible alcohol dehydrogenase (ADHII), has been isolated by complementation of function in transformed yeast. The chromosomal DNA from nine yeast strains with cis-dominant constitutive mutations (ADR3c) has been investigated by restriction enzyme analysis, using the cloned ADR2 DNA as a hybridization probe. Seven mutants appear to have insertions of approximately 5.6 kg near the 5' end of the ADR2 coding region. Four of these insertions have the same restriction pattern as the yeast transposable element Ty1. Two differ from Ty1 by the presence of an additional Hind III site, and a seventh insertion differs from Ty1 at a number of restriction sites. All are inserted in the same orientation with respect to the structural gene. A DNA fragment containing the ADR2 gene and adjacent sequences from a constitutive mutant has been cloned and shown by heteroduplex analysis to contain an insertion near the 5' end of the structural gene. The cloned insertion sequence hybridizes to multiple genomic DNA fragments, indicating that it contains a moderately repetitive sequence. Thus it appears that insertion of a transposable element near the 5' terminus of the structural gene can produce constitutive expression of a normally glucose-repressed enzyme. Such insertions seem to be the most common way of generating cis-dominant constitutive mutations of ADHII. PMID- 6258807 TI - Anti-phosphorylcholine antibody-producing cells in human lymphoblastoid cell lines established by transformation with Epstein-Barr virus. PMID- 6258808 TI - Adenosine kinase activity during in vitro culture of human peripheral blood monocytes and pulmonary alveolar macrophages. PMID- 6258810 TI - Mechanism of Epstein-Barr virus-induced human B-lymphocyte activation. PMID- 6258809 TI - Cellular immune responses of mice to influenza virus infection. PMID- 6258811 TI - Immunity to herpes simplex virus type 2 (HSV-2). I. Development of virus-specific lymphoproliferative and leukocyte migration inhibition factor responses in HSV-2 infected guinea pigs. PMID- 6258812 TI - [Properties of poliovirus detected in waste waters in the administration of nonhomogeneous vaccine (author's transl)]. PMID- 6258813 TI - [Ocular metastasis of bronchial carcinoid (author's transl)]. PMID- 6258814 TI - [Treatment of glass grinders' ulnar acroparesthesia using Bernard's (diadynamic) currents]. PMID- 6258815 TI - [Epstein-Barr virus in the environment of patients with Hodgkin's disease]. PMID- 6258816 TI - [Extracerebral etiology of a seizure disorder]. PMID- 6258817 TI - [Effect of age and sex on antibody formation]. PMID- 6258819 TI - [Differential diagnosis of some skin diseases with pathological intraepidermal heteromorphic cell clumps (author's transl)]. PMID- 6258818 TI - Potent induction of rat liver microsomal, drug-metabolizing enzymes by 2,3,3',4,4',5-hexabromobiphenyl, a component of fireMaster. AB - The multistep synthesis and purification of 2,3,3',4,4',5-hexabromobiphenyl (HBBp) is described. Capillary gas chromatography revealed that HBBp comprises 0.05% of the industrial polybrominated biphenyl (PBB) mixture, fireMaster BP-6 (lot 7062). When administered to immature male Wistar rats, HBBp caused a dose dependent increase in (a) the activity of benzo[a]pyrene (B[a]P) hydroxylase (AHH) and 4-chlorobiphenyl (4-CBP) hydroxylase and (b) the concentration of cytochrome P-450. Sodium dodecyl sulfate (SDS)-gel electrophoresis indicated that these increases in cytochrome P-450 and cytochrome P-450-dependent monooxygenase activities were accompanied by a dose-dependent intensification of a protein of relative molecular weight (Mr) 55 000 which comigrated with the major 3 methylcholanthrene(MC)-inducible form of cytochrome P-450 (i.e., cytochrome P 448). Like MC, but in contrast to phenobarbitone (PB), HBBp competitively displaced 2,3,7,8-[3H]tetrachlorodibenzo-p-dioxin ([3H]-TCDD) from the cytosolic protein thought to be the receptor for cytochrome P-448 induction. The results indicate that HBBp is a potent inducer of cytochrome P-448 and as such is the third MC-type inducer identified in fireMaster BP-6. PMID- 6258820 TI - [Effects of the dihydroxyl metabolites of vitamin D3 and their ethanol solvent on parathyroid secretion: in vivo study in the rat]. AB - The regulation of parathyroid secretion by the vitamin D3 dihydroxylated metabolites was studied by differents authors. In vitro experiments showed that 1 alpha (OH)2 D3 and 24 R 25 (OH)2 D3 inhibited the PTH release. In Rats maintained in a normal calcium diet or calcium and/or vitamin D deficient diet, 1 alpha 25(OH)2 D3 and 24 R 25 (OH)2 D3 inhibited the PTH release, whereas 24 S 25 (OH)2 D3, 25 S 26 and 25 R 26(OH)2 D3 had no effect. PMID- 6258821 TI - [Variations of the sum of the arterial partial pressure of inert gases during changes in the composition of inhaled gas without a variation of the ambient pressure, in a hyperbaric atmosphere]. AB - In hyperbaric environments, when inhaled inert gas composition is abruptly modified, the sum of the arterial inert gases partial pressures is different to the sum of these same gases in the inhaled mixture. While switching from a helium oxygen to a nitrogen-oxygen mixture of same P1O2 and total pressure, the sum of the arterial inert gas partial pressure was transiently less than the one in the inspired gases: there was an arterial under-saturation: PaHe + PaN2 = 0.68 (P1He + P1N2). During the opposite switch (from nitrogen to helium), a reversed time course, namely a transient over saturation, was observed: PaHe + PaN2 = 1.31 (P1He + P1N2). Amongst the different possible explanatory hypotheses, the most probable is that inert gas partial pressure equilibrium through the alveolo capillary membrane is not achieved when the blood leaves the pulmonary capillary. PMID- 6258822 TI - Fluorescent spot test for detecting carbohydrate-splitting enzymes in meconium. AB - I describe a fluorescent spot test for detecting the acidic glycosidases in meconium. Meconium is mixed with various 4-methylumbelliferylglycosides at the appropriate pH. In the presence of carbohydrate-splitting enzymes, 4 methylumbelliferone, a strongly fluorescent compound, is released. The reaction mixture, when spotted on chromatography paper and viewed under ultraviolet light, exhibits a bright fluorescence for specimens containing acidic glycosidases. The technique is applicable to any test that involves production of fluorescent products from non-fluorescent reactants. The procedure was applied to meconium specimens selected because of increased albumin content known to be associated with cystic fibrosis in newborns. The presence of beta-D-fucosidase in meconium was correlated to increased albumin content. Detection of beta-D-fucosidase by the present procedure may be useful as a screening test for cystic fibrosis. PMID- 6258823 TI - Colorimetric determination of serum 5'-nucleotidase without deproteinization. AB - We present a sensitive colorimetric determination of 5'-nucleotidase based on the measurement of liberated phosphate by reaction with stannous chloride/molybdenum blue. No protein precipitation is required. The method is simple, sensitive, economical, and easy to use, and involves relatively stable reagents. PMID- 6258824 TI - Characterization of a spectrophotometric assay for angiotensin converting enzyme. AB - Although serum angiotensin converting enzyme (EC 3.4.15.1) activity has generally been shown to be increased in patients with sarcoidosis, considerable variation in the diagnostic usefulness of this test has been reported. We investigated the possibility that this variation may be the result of inhibition of the widely used spectrophotometric assay by various substances. We also prospectively examined the predictive value of measurements of this enzyme in serum from 100 patients being evaluated for sarcoidosis. The following did not significantly affect the results: storage at 4 or 25 degrees C for one week, hemoglobin, lipoproteins, or corticosteroid medications. Bilirubin, at concentrations of 20 mg/L of serum or move, significantly inhibited the assay. Sera with increased activity showed nonlinear reaction rates during the usual 60-min reaction interval, This was corrected by shortening the reaction time to 30 min. We found a predictive value of 88% when the serum angiotensin converting enzyme test was applied to the diagnosis of active sarcoidosis. PMID- 6258825 TI - 125I radioimmunoassay of delta-9-tetrahydrocannabinol in blood and plasma with a solid-phase second-antibody separation method. AB - In this sensitive and specific radioimmunoassay for delta-9-tetrahydrocannabinol, an iodinated tracer with high specific activity and a solid-phase separation are used. Within-run coefficients of variation for 5.0 and 30.0 microgram/L concentrations were 7.8 and 4.2% for plasma and 14 and 10.6% for hemolyzed blood specimens, respectively. Day-to-day coefficients of variations ranged from 7.3 to 13.6% (for 7.6 to 33.0 microgram/L concentrations) for plasma and 13.4 to 18.1% (3.0 to 52.1 microgram/L) for hemolyzed blood specimens. Data for time after start of smoking of a standard THC-containing cigarette vs the concentration of delta-9-tetrahydrocannabinol in the plasma were similar to those obtained by others. Positive plasma specimens from the smoking study were analyzed by gas chromatography-mass spectrometry and by our radioimmunoassay. Nonparametric statistical comparison and linear regression (r2 = 0.972) showed that results by the two methods of analysis correlate well. The sensitivity of the assay was at least 0.3 microgram/L for plasma, 1.1 microgram/L for hemolyzed blood. PMID- 6258826 TI - Enzymes of lysosomal origin in human plasma and serum: assay conditions and parameters influencing the assay. AB - The condition for maximal activity (pH, buffer, saturating substrate concentration, range of linear relationships between enzyme activity versus incubation time, and versus enzyme concentration) in the fluorimetric assay of several glycohydrolases of lysosomal origin in human plasma and serum have been established. The following enzymes were studied: alpha-galactosidase, beta galactosidase, beta-N-acetylglucosaminidase, beta-glucosidase, beta glucuronidase, alpha-mannosidase, alpha-fucosidase. All examined enzymes turned out to be more or less unstable upon storage at 37 degrees C, 4 degrees c, and 20 degrees C in both serum and plasma. The only exceptions were beta glucuronidase, which was stable in plasma and serum, and alpha-fucosidase which was stable only in plasma. Generally the degree of instability was greater in serum than in plasma. The levels of some enzymes (alpha-galactosidase, beta galactosidase, beta-N-acetyl glucosaminidase, beta=glucuronidase) were markedly higher in serum than in plasma; conversely the levels of the same enzymes in "platelet free" serum equalled those in plasma. This stresses the necessity to use freshly prepared plasma for lysosomal glycohydrolase assay. Under the procedural conditions recommended for the assay the methods for the determination of lysosomal glycohydrolases in plasma appeared to be simple, sensitive and reproducible. PMID- 6258827 TI - Radioimmunoassay of extracted glucagon compared with three non-extraction assays. AB - Radioimmunoassay of glucagon was performed with three different antisera, i.e. E7, 30K and 4305, all directed against the carboxyl-terminal region of glucagon and thus avoiding co-determination of glucagon-like polypeptides from the gut. Plasma samples from five healthy people subjected to various A-cell stimulation and suppression tests were used and immunoreactive glucagon assessed with the three antisera. Aliquots from all plasma samples were also extracted with acetone and glucagon re-assessed with antiserum E7. Even though all four baseline glucagon concentrations obtained were different, the glucagon profiles were comparable after superimposing the baselines. The differences in baseline concentrations of immunoreactive glucagon seem due to the interference of "big plasma glucagon", a still unidentified factor in the E7 and 30K assays that can be precipitated by acetone. Since acetone extraction yielded the lowest baselines without altering the glucagon profiles, it is suggested that the baseline glucagon concentrations of acetone-extracted plasma reflect the physiological level of the biologically active hormone. Using antiserum E7, our own antiserum, the normal range of glucagon values in acetone-extracted plasma samples from 22 healthy, fasting people of both sexes was 42 +/- 16 ng/l (mean +/- 2 S.D.). These values agree well with those obtained by other assay techniques. PMID- 6258829 TI - Alpha 1-antitrypsin in patients with hepatocellular carcinoma and chronic active hepatitis. AB - Forty-seven Italian patients suffering from hepatocellular carcinoma (HCC) and 58 patients with chronic active hepatitis (CAH) were screened for alpha 1 antitrypsin (alpha 1 AT) levels and types and compared with a previously screened healthy Italian population. Serum alpha 1 AT concentrations were significantly raised among the HCC patients compared to the controls, whereas the CAH group showed no differences. The incidence of non-M phenotypes (MS, MZ and S) is significantly higher in patients with HCC than in the CAH group and the controls. The mean age of HCC patients with a non-M phenotype is significantly lower than the mean age of HCC patients with an M phenotype. PMID- 6258828 TI - Increased urine angiotensin I converting enzyme activity in patients with upper urinary tract infection. AB - Angiotensin converting enzyme (ACE) is present within the brush border of the tubular cell of the kidney. Since it has a high molecular mass, ACE activity of urine most probably derives only from tubular cells, thus suggesting the potential usefulness of ACE determination as an index of tubular damage. When assayed with the method described, ACE is optimally active at pH 8 with a calcium concentration exceeding 0.75 mmol/l urine, and is chloride independent. Urine dialysis has no effect on ACE activity. ACE is stable at 4 degrees C for 10 days, but it is inactivated by repeated thawing and freezing. The presence of leucocytes and bacteria does not interfere with the assay. Urine ACE activity was evaluated in patients with upper and lower urinary tract infection, nephrolithiasis, chronic glomerulonephritis and essential hypertension and was found to be significantly increased only in patients affected by upper urinary tract infection and nephrolithiasis. PMID- 6258830 TI - Metabolic and cytoskeletal modulation of transferrin receptor mobility in mitogen activated human lymphocytes. AB - The transferrin receptors which appear on mitogen-activated human peripheral blood lymphocytes were found by the use of immunofluorescence techniques to display temperature-dependent patching and capping reactions upon binding of transferrin. Lateral mobility of ligand-occupied membrane sites was accompanied by both shedding and endocytosis of receptor-transferrin complexes. In the presence of sodium azide or the microfilament inhibitor cytochalasin B, cap formation and shedding were markedly inhibited. In contrast, endocytosis of patched receptor-ligand complexes was inhibited by azide and microtubule inhibitors, including colchicine, vinblastine and vincristine. Co-capping experiments performed to elucidate further the alterations in membrane configuration involved in these reactions failed to reveal any topographical relationship between transferrin receptors and lectin-binding sites in these cells. These studied indicate that temperature-dependent mobility of transferrin receptors upon mitogen-activated peripheral blood lymphocytes is dependent upon the integrity of the cytoskeletal system and metabolic function of the cell. PMID- 6258831 TI - Effects of isoprenaline, levodopa and a phosphodiesterase inhibitor (ICI 63,197) on cyclic AMP levels and contractions of soleus muscles in anesthetized cats. AB - 1. Cyclic AMP levels have been determined in the soleus muscles of anaesthetized cats in the absence of drugs, and during depression of incomplete tetanic contractions produced by (-)-isoprenaline, ICI 63,197 (a phosphodiesterase inhibitor) or levodopa. 2. Cyclic AMP levels were elevated at the peak of tension depression produced by isoprenaline. Effects of isoprenaline on cyclic AMP and on contractions were dose dependent and statistically significantly related one to the other. Both effects were blocked by propranolol. 3. ICI 63,197 and levodopa produced isoprenaline-like effects on contractions but times to peak effect and recovery were longer. Cyclic AMP levels estimated during the depressant action were elevated. 4. The results support the involvement of cyclic AMP in the depressant effect of beta-adrenoreceptor agonists on slow-contracting mammalian skeletal muscle. PMID- 6258832 TI - Baroreceptor reflex in the rat after converting enzyme inhibition or angiotensin receptor blockade. AB - 1. One component of baroreflex responsiveness was quantitated in conscious rats using the heart rate response to a pressor injection of phenylephrine. 2. Endogenous angiotensin and its effectiveness were manipulated by sodium deprivation, converting enzyme inhibition and infusion of an angiotensin analogue. None of these manoeuvres changed the observed reflex responsiveness. 3. We conclude that endogenous angiotensin has no influence on the component of baroreceptor function that is described by the slope of the arterial pressure heart rate relationship. PMID- 6258833 TI - The thymus in the aging individual. II. Thymic epithelial function in vitro in aging and in thymus pathology. PMID- 6258834 TI - Production of human leukocyte migration inhibitory factor (LIF) by lymphocytes stimulated with phytohemagglutinin. II. Effects of cyclic nucleotides. PMID- 6258836 TI - Induction of ecto-5'-nucleotidase activity in human thymocytes. PMID- 6258835 TI - Complement-induced entry o f membrane-impermeable material into living tumor cells: possibilities for chemotherapy. PMID- 6258837 TI - Unaltered lymphocyte beta-adrenoceptor responsiveness in hyperthyroidism and hypothyroidism. AB - Beta adrenoceptor sensitivity may be altered in thyrotoxicosis and myxedema. We therefore studied beta-adrenoceptor responses of peripheral blood lymphocytes to stimulation with 10(-9) to 10(-6) M (-)-isoproterenol from patients before and after treatment of myxedema and thyrotoxicosis as well as in patients without thyroid disease. There were six patients in each group. Lymphocyte basal cyclic adenosine monophosphate (cAMP) concentrations were higher in untreated thyrotoxicosis (4.94 +/- 0.46 pmole/10(6) cells) than in controls (3.47 +/- 0.42 pmole/10(6) cells, p less than 0.05) and in untreated myxedema (3.11 +/- 0.50 pmole/10(6) cells, p less than 0.025). The full isoproterenol dose-response curves were similar in all groups. Calculated maximum velocity (Vmax) showed an approximate increase in cAMP of 14.5 pmole/10(6) cells. Isoproterenol concentrations at half-maximum velocity (EC50) were approximately 10(-8) M. It is concluded that lymphocyte beta 2-adrenoceptor responses are not altered in hypothyroidism and hyperthyroidism. PMID- 6258838 TI - Effect of atenolol, metoprolol, and propranolol on isoproterenol-induced tremor and tachycardia in normal subjects. AB - The effect of single oral doses of atenolol (100 mg), metoprolol (100 mg), propranolol (40 mg), and placebo on exercise tachycardia and on heart rate and finger tremor responses to graded injections of isoproterenol was investigated in six normal subjects. Propranolol was more potent than atenolol and metoprolol in suppressing the increase in heart rate and tremor amplitude produced by isoproterenol, even though at the dose used it was the least effective of all three drugs in decreasing exercise tachycardia. Although these data are consistent with the hypothesis that the suppression of isoproterenol-induced tremor is mediated by antagonism of peripheral beta 2-adrenergic receptors, the possibility that a separate action other than beta-blockade may contribute to the tremorolytic action of propranolol cannot be excluded. The potential usefulness of examining the effect of beta-adrenoceptor blocking drugs on isoproterenol induced tremor and tachycardia in cardioselectivity studies is discussed. PMID- 6258839 TI - Plasma renin activity and plasma concentrations of norepinephrine and cyclic nucleotides in heart failure after prazosin. AB - A single oral dose of 1.0 to 2.0 mg prazosin was given to 14 patients with congestive heart failure to assess its effect. Prazosin increased cardiac index (+27.5%) and decreased pulmonary arterial diastolic pressure (-29.1%), systemic vascular resistance (-27.7%), mean blood pressure (-11.8%), and double products ( 12.9%). Plasma renin activity (?.8%) and plasma concentrations of norepinephrine (+67.5%) and cyclic adenosine monophosphate (AMP) (+10.6%) rose. There was a negative correlation between plasma cyclic AMP concentration and the increase of plasma cyclic AMP concentration after prazosin (Y = -0.53X + 18.7). There were no changes in heart rate and plasma cyclic guanosine monophosphate concentration. The effects were maximum at 3 hr and lasted 5 hr. The results indicate that oral prazosin has a beneficial hemodynamic effect in patients with congestive heart failure, and that the pathologic effects of prazosin, "alpha-blocker." induces a rise in plasma renin activity as well as in plasma concentrations of norepinephrine and cyclic AMP. PMID- 6258840 TI - Paget's disease of the breast: a case report. PMID- 6258841 TI - Viral infections of the skin. PMID- 6258842 TI - [Introduction to influenza viruses (author's transl)]. PMID- 6258844 TI - The epidemiology and ecology of swine influenza as a zoonotic disease. PMID- 6258843 TI - [European Pharmacopoeia and the test of equine influenza vaccines (author's transl)]. PMID- 6258845 TI - [Incidence of influenza infections in pigs (1977-1979). serological survey (author's transl)]. PMID- 6258846 TI - Some epidemiological and virological relationships between human and animal influenza. PMID- 6258847 TI - Principles for production of effective defined subunit vaccines. Deduction from a model experiment. PMID- 6258848 TI - The role of WHO in international studies on the ecology of influenza in animals. PMID- 6258849 TI - Equine influenza--a segment in influenza virus ecology. PMID- 6258850 TI - [World-wide circulation of information concerning equine influenza. (Note FROM AN O.I.E. working party on horse diseases) (author's transl)]. PMID- 6258851 TI - Epidemiology of equine influenza, risk by age, breed and sex. PMID- 6258852 TI - [Recent epidemic of equine influenza in France (author's transl)]. PMID- 6258853 TI - [Hemagglutination test applied to equine influenza. A study of some parameters (author's transl)]. PMID- 6258854 TI - [Simple, simultaneous or combined vaccinations of horses against equine influenza, rabies and tetanus (author's transl)]. PMID- 6258855 TI - Cell-mediated immunity in cytomegalovirus infections--a review. PMID- 6258856 TI - Application of a radioimmunoassay for detection of the major internal antigen (p24) of bovine leukemia virus from cultured lymphocytes of cattle. PMID- 6258857 TI - Cell-mediated immunity in mouse experimental Coxsackie A9 virus infection. PMID- 6258858 TI - Serological comparison of Bovid herpesvirus 2 and Herpes simplex virus by reciprocal neutralization kinetic studies. PMID- 6258859 TI - Biosynthesis of transfer RNA. PMID- 6258860 TI - Chemiluminescence of phagocytic cells. PMID- 6258861 TI - Comparison of CT scanning and radionuclide imaging in liver disease. AB - Early experience with body CT suggested its usefulness in many diagnostic problems; jaundice, renal and pancreatic masses, and in the evaluation of relatively inaccessible parts of the body, such as the retroperitineum, mediastinum, and pelvis. Investigation of hepatic disease by CT was not unexpectedly compared to radionuclide liver scanning, the major preexisting modality for imaging the liver. In the evaluation of the jaundiced patient, CT rapidly assumed a major role, providing more specific information about the liver than the RN liver scan, as well as demonstrating adjacent organs. CT differentiate obstructive from non-obstructive jaundice, and frequently the cause of the obstructive jaundice. With respect to mass lesions of the liver, the RN liver scan is more sensitive than CT but less specific. The abnormalities on an isotope image of the liver consist of normal variants in configuration, extrinsic compression by adjacent structures, cysts, hemangiomata, abscesses, and neoplasms. These suspected lesions may then be better delineated by the CT image, and a more precise diagnosis made. The physiologic information provided by the RN liver scan is an added facet which is helpful in the patient with diffuse hepatic disease. The CT image will be normal in many of these patients, however, hemochromatosis and fatty infiltration lend themselves especially to density evaluation by CT. The evaluation of lymphoma is more thorough with CT. Structures other than the liver, such as lymph nodes, are visualized. Gallium, however, provides additional isotopic information in patients with lymphoma, and in addition, is known to be useful in the investigation of a febrile patient with an abscess. Newer isotopic agents expand hepatic imaging in other directions, visualizing the biliary tree and evaluating the jaundiced patient. PMID- 6258862 TI - Differentiation of excitable membranes. PMID- 6258863 TI - Nerve growth factors and control of nerve growth. PMID- 6258864 TI - Release of lactate dehydrogenase during isolation of adult rat heart cells. AB - In order to determine the least injurious method of cell isolation, effluent perfusates from isolated rat hearts were examined for lactate dehydrogenase activity during cellular isolation procedures. Correlation of these results with the perfusates, with modifications in the perfusates, and with the yield of intact cells isolated, indicated that perfusion of isolated hearts with solutions containing bovine serum albumin and/or collagenase can result in severe cellular injury. These effects were significantly modified by the presence of calcium ion. These results indicated that the concentration of calcium ion during isolation is critical to successful isolation of calcium tolerant, functional adult heart cells. PMID- 6258865 TI - Chromosomal DNA homologous to Herpes simplex virus 1 in a mouse L-cell line. AB - Cytological hybridization in situ was used to identify chromosomes carrying DNA sequences homologous to Herpes simplex I (HSV-I) DNA in a HSV-transformed L-cell line. The L-cell karyotype, frequency of chromosome distribution, and possible homology to the normal chromosome complement are given. The major chromosomal sites for transcription of ribosomal RNA (rRNA) were also determined. PMID- 6258866 TI - [Evaluation of the effect of the preparation, Pulpomixine, used for indirect covering of inflamed dental pulp in dogs]. PMID- 6258867 TI - [Usefulness of thermographic studies for the diagnosis of parotid gland tumors]. PMID- 6258868 TI - Diffuse pneumonitis due to adenovirus type 21 in a civilian. AB - A patient with severe pneumonitis due to adenovirus type 21 responded to oxygen delivered by continuous positive airway pressure through a face mask. Pulmonary function studies over ten months demonstrated resolving, restrictive lung disease. The prognosis of severe adenovirus pneumonia may be better than expected based on previous reports. PMID- 6258869 TI - Simple radioassay for measuring serum activity of angiotensin-converting enzyme in sarcoidosis. PMID- 6258870 TI - Rapidly progressing diffuse pulmonary infiltrate. PMID- 6258871 TI - A controlled clinical trial testing two potentially non-cross-resistant chemotherapeutic regimens in small-cell carcinoma of the lung. AB - With the objectives of improving response rate, duration of response, and survival in small-cell carcinoma of the lung, 39 patients were randomized to remission-induction with either one of two potentially non-cross-resistant drug combinations: APE (consisting of adriamycin, 35 mg/m2 IV, D1 Q 3 weeks; procarbazine, 60 mg/m2 PO, D1-10 Q 3 weeks; and the epipodophyllotoxin (VP16 213), 130 mg/m2 IV, D8, 15 Q 3 weeks) or MOCC (composed of methotrexate, 15 mg/m2 IV (with [vincristine] Oncovin) or PO twice weekly D8-21 Q 3 weeks; Oncovin, 1.5 mg/m2 IV, D8, 15 Q 3 weeks; cyclophosphamide, 600 mg/m2 IV, D1 Q 3 weeks, and CCNU, 60 mg/m2 PO Q 6 weeks). A fixed crossover to the alternate regimen occurred at three months. Radiotherapy was delivered to the primary tumor (locoregional disease only) by a split course technique (1,750 rads for five days with a three week split, followed by 3,400 rads over 17 days). The median survival including both arms was 11 months for regional and nine months for extensive disease. The chemotherapeutic activity of both regimens was comparable, with 15/17 (88 percent) of the patients responding to APE (including six complete) and 14/17 (82 percent) responding to MOCC (including five complete). The median survival for the complete responders was 11.7 months, while the partial responders survived for a median of 9.7 months. There were 2/9 (22 percent) responders to the alternate regimen at progressive disease. The overall incidence of CNS progression was 17 percent. The toxicity of the regimens was moderate, except for one instance of granulocytopenic death. This study establishes two equipotent drug combinations for the treatment of small-cell carcinoma of the lung. PMID- 6258873 TI - [In vivo studies on the tensile strength loss of absorbable synthetic threads]. AB - In a total of eight experimental groups, PGS, PGS-S, PGS-C, and polyglactin 910 sutures were implanted subcutaneously in rats. The sutures were either sterile or contaminated with staphylococcus. They were removed after 7, 14, 21, and in two groups after 28 days. The linear loss of tensile strength was tested by means of an electronic tensile strength measuring machine. In four additional groups, the same studies were carried out with paraffinized PGS sutures and in localizations in stomach, duodenum and colon. The diameter of the filament has an effect on the loss of tensile strength: initially more rapid in fine filaments and later, retarded in comparison to thicker filaments. Coating of the suture has almost no influence on tensile strength, although contaminated sutures show a comparative decrease. In intraenteral localizations, loss of tensile strength can be expected to occur much more rapidly than in subcutaneous ones. Paraffinization does not delay decrease in tensile strength. Polyglactin 910 sutures of the second generation employed subcutaneously, show a much higher loss of tensile strength on the day 7 than PGS sutures; by day 28 the relationship is reversed. PMID- 6258872 TI - Appraisal of disk sensitivity tests with mecillinam. AB - Disk susceptibility tests for mecillinam were carried out on 167 hospital isolates of Enterobacteriaceae from Vancouver. Inhibition zone sizes with eight experimental variations were compared by three-way analysis of variance. The Association of Clinical Pathologists' method gave significantly (p = 0.0002) larger zones than the Kirby Bauer method (24.9 +/- SD 7.5 and 23.4 +/- 7.3 mm, respectively). 10 microgram mecillinam disks from Mast Laboratories gave significantly (p = 0.0004) larger zones than the Baltimore Biological Laboratories (BBL) equivalent (24.9 +/- 7.6 and 23.4 +/- 7.2 mm, respectively). Differences between Oxoid Iso-sensitest agar and BBL Mueller Hinton agar were not quite significant (24.5 +/- 7.9 and 23.8 +/- 6.9 mm, respectively, p = 0.061). Each disk test method was significantly different from at least one other (Duncan multiple range test, alpha = 0.05). A semilogarithmic regression was established between the antibiotic disk inhibition zone and the MIC for each experimental variation. BBL Mueller Hinton and Oxoid Iso-sensitest media did not give significantly different results in MIC determinants by a surface inoculation method. An additional 146 organisms from hospitals in New York provided a wider range of organisms from a different location. Pooled data from both centres were used to identify breakpoints for mecillinam in the disk susceptibility test using the Kirby Bauer method with BBL disks and media. A 16-mm breakpoint with 10 microgram mecillinam disks provides a realistic and conservative prediction of probable response to attainable serum concentrations of this antibiotic. PMID- 6258874 TI - [Perforated liver tumor as cause for intraabdominal bleeding]. PMID- 6258875 TI - [Quantitative diagnosis of trophoblastic cell diseases (author's transl)]. PMID- 6258876 TI - Comparison of the nuclear ribosomal units of five Chlamydomonas species. AB - The organization of the nuclear ribosomal units of five different species of Chlamydomonas has been examined by hybridization of their nuclear DNA fragments produced by several restriction endonucleases with a radioactively labelled probe consisting of the two cloned BamHI ribosomal fragments of C. reinhardii. The results indicate that a) the ribosomal units of these five species are structurally related, b) changes in the non transcribed spacer occur in C. eugametos and in C. globosa, c) the rDNA unit of C. intermedia contains either an enlarged internal transcribed spacer or a ribosomal intervening sequence, d) the rDNA units of C. reinhardii and C. callosa are indistinguishable. PMID- 6258877 TI - The distribution of repetitive DNAs between regular and supernumerary chromosomes in species of Glossina (Tsetse): a two-step process in the origin of supernumeraries. AB - Several species of tsetse fly within the Morsitans and Fusca subgenera of Glossina contain supernumerary (B) chromosomes. Previous studies on the meiotic behaviour of chromosomes (Southern and Pell, 1973) and the C-band patterns (Jordan et al., 1977) have indicated a close similarity between the Y chromosome and the supernumeraries. The distributions of the highly abundant families of DNA (satellite DNAs) between the autosomes, sex chromosomes and B chromosomes of G.m. morsitans, G. austeni and G. pallidipes have been examined by in situ hybridisation. In addition, the organisation and sequence homologies of satellite DNAs have been examined by restriction enzymes and heterologous hybridisations in in situ and "Southern" transfer conditions. The majority of satellite sequences that are homologous between species are distributed in several different arrangements between A and B chromosome telomeres with minority sequences at some centromeric and intercalary locations. There is no extensive satellite DNA similarity between the Y and B chromosomes. We suggest that the Y and B chromosome associations and synchronous allocycly during meiosis are the result of extensive heterochromatinisation of these two chromosome types, that is probably a reflection of two separate stages involved in the generation of the B chromosomes in the genus. The independent evolution of satellites and supernumeraries is discussed. PMID- 6258878 TI - The fate of circulating biologically active peptides in the lungs. AB - The factors which regulate the disappearance of endogenous active substances during pulmonary transit are discussed. The presence of hydrolytic enzymes in the cytosol is not the only factor regulating pulmonary metabolism. An uptake transport process is required to permit access to intracellular enzymes. No endothelial cell transport mechanism has yet been described for peptides. However, bradykinin and angiotensin I are metabolized by the pulmonary circulation because the enzyme is localized on the luminal surface of the endothelial cells. The pulmonary and extrapulmonary conversion of angiotensin in rat is still a matter of debate. Evidence is presented which supports the idea that when low doses of angiotensin I (greater than 10 ng) are given intravenously, most of the conversion is pulmonary. With higher doses, extrapulmonary conversion also contributes to the final pressor effect of angiotensin I. PMID- 6258879 TI - Interrelationships between prostacyclin and thromboxane A2. AB - Prostacyclin is a product of arachidonic acid metabolism generated by the vessel wall of all mammalian species studied including man. Prostacyclin is a potent vasodilator and the most potent inhibitor of platelet aggregation so far described. It inhibits platelet aggregation through stimulation of adenylate cyclase leading to an increase in cyclic AMP in the platelets. The enzyme which synthesizes prostacyclin is mainly localized in the endothelial layer of the vascular wall. Prostacyclin can also be a circulating hormone constantly released by the pulmonary circulation. On the basis of these observations we proposed that platelet aggregability in vivo is controlled via a prostacyclin mechanism. In contrast to the vessel wall, in blood platelets arachidonic acid is converted by the enzyme thromboxane synthetase to a potent vasoconstrictor and proaggregating substance, thromboxane A2. Therefore arachidonic acid is metabolized in the vessel wall and the platelets to potent substances with opposing biological activities. The balance between the activities of these substances is important in the homeostatic interaction of the platelets and the vessel wall. The different ways of interfering with this balance and its impact in the development of thrombosis and atherosclerosis are discussed. The balance between thromboxane A2 and prostacyclin might be important in the control of the pulmonary circulation. This possibility is discussed in the light of the present evidence. PMID- 6258881 TI - Pulmonary angiotensin-converting enzyme and its inhibition: a historical survey. AB - Angiotensin-converting enzyme, the peptidase hydrolysing angiotensin I to angiotensin II and first discovered in plasma, has been demonstrated in lung tissue on the luminal surface of endothelial cells lining pulmonary blood vessels. Because converting enzyme is the final activating step in the renin angiotensin system its inhibition prevents the pressor and other effects of increased renin secretion. Lung converting enzyme activity is inhibited specifically by a nonapeptide (BPP9a:SQ 20 881) contained in Bothrops jararaca venom. This peptide inhibits the pressor effects of injected angiotensin I in humans and lowers blood pressure in patients with high-renin hypertension. Recently a synthetic inhibitor, captopril, was devised which is effective, given orally, in reducing the blood pressure of high-renin hypertensives and of a proportion of hypertensives with normal renin levels. The latter finding suggests that blood pressure may be maintained by renin-dependent mechanisms without increased renin secretion. PMID- 6258880 TI - Endocrine influences on aspects of lung biochemistry. AB - Evidence is presented that the postnatal rat lung is receptive to several hormones. Experimental diabetes caused a significant depression in lung glucose oxidation rate which was normalized by exogenous insulin therapy. Diabetes also depressed the rate of amino acid incorporation into lung protein; in vitro, insulin stimulated synthesis of selective protein species by the diabetic lung. These results, together with the demonstration of pulmonary receptor sites for insulin and the observation that diabetes selectively affects the ultrastructure of only two cell types in the lung, suggest that insulin may be an important regulator of lung function. That androgens and oestrogens may also exert an effect on the lung is suggested by the presence of distinct receptor activities for these hormones, which appear to be influenced by serum titres of the gonadal steroids. The lung is capable of generating a considerable amount of cyclic GMP in vitro. This ability appears to be dependent upon continued protein synthesis and is influenced by the endocrine state of the animal. Certain steroid hormones are capable of altering cyclic GMP production by the lung when introduced in vitro. PMID- 6258882 TI - Modulation of converting enzyme activity by hypoxia and its physiological effects. AB - To explore the haemodynamic consequences of the reduction in converting enzyme activity by acute alveolar hypoxia we made sequential haemodynamic observations in seven saline-infused and 12 bradykinin-infused anaesthetized, catheterized dogs. They were ventilated initially with room air and then for 50 minutes with hypoxic gas mixtures. Within two minutes after starting hypoxic ventilation, converting enzyme activity decreased, arterial angiotensin II concentrations dropped, and, in the bradykinin-infused dogs, arterial bradykinin concentrations rose. Both groups of dogs experienced a rise in systemic and pulmonary arterial blood pressure in response to hypoxia, but by different mechanisms. In the saline infused (control) dogs there was increased systemic (+40%) and pulmonary (+90%) vascular resistance while cardiac output was unchanged or slightly reduced. Bradykinin-infused dogs demonstrated reduced systemic vascular resistance (-40%), no increase in pulmonary vascular resistance and a 100% increase in cardiac output. Return to room air breathing restored converting enzyme activity, releasing high concentrations of angiotensin II. Oxygen tension thus regulates converting enzyme activity and hence the circulating levels of angiotensin II and bradykinin. PMID- 6258884 TI - Prostaglandin receptors in the airways. AB - An analysis of the effects of some natural prostaglandins and of synthetic analogues with more selective actions points to the existence of several receptors for prostaglandins in the airways. Three effects have been studied: the contraction and relaxation of bronchial smooth muscle in vitro and the cough elicited by inhalation of prostaglandin aerosols by the conscious cat. From the rank orders of potency of a group of prostaglandins and analogues, from tachyphylaxis induced by continued exposure to a single species and from antagonism by indomethacin or mefenamic acid, three prostaglandin receptors have been distinguished: (1) for contraction (chi receptor) and (2) for relaxation (psi receptor) of bronchial smooth muscle, and (3) for cough (omega receptor). The natural prostaglandins tested stimulated to different extents each of these three receptors; but synthetic analogues with selective actions on only one or two receptors were identified. It seems likely that (1) prostaglandins or thromboxanes not yet tested will interact with these receptors, (2) other receptors for these substances may be distinguished in the airways, (3) the receptors so far distinguished may also be found in other sites, and (4) the receptor categories described may be subdivisible. PMID- 6258883 TI - Non-respiratory functions of the lung in the perinatal period. AB - Beginning with the hypothesis that interference with the metabolic function of the lung could lead to perinatal respiratory disease, we explored the role of one of these functions, angiotensin-converting enzyme activity, in the control of the fetal and newborn circulation. Converting enzyme regulates the concentration of two peptides, bradykinin and angiotensin, important in adapting the fetus to extrauterine life. Initial studies demonstrated decreasing amounts of converting enzyme activity and a parallel decrease in vascular surface with decreasing gestational age. Because we had demonstrated that there is little converting enzyme activity at the low PO2 values of the fetus we examined the fetal placental unit and found that the placenta is the predominant site of converting enzyme activity in utero and this activity is modulated by maternal PO2. We also found that such pathophysiological accompaniments of premature birth as chilling and acidosis can stimulate the kallikrein-kinin system into overactivity. Because the kallikrein-kinin and renin-angiotensin systems are so closely interrelated with other vasoactive substances, an imbalance in production and degradation is likely to produce some of the pathophysiology seen with premature birth, including systemic hypotension, coagulopathy and oedema. PMID- 6258885 TI - Superoxide dismutases. AB - Superoxide dismutases (EC 1.15.1.1) are metalloenzymes that catalytically scavenge the superoxide radical. They are essential for the aerobic survival of all forms of life. There are three types of superoxide dismutase, containing manganese, iron, or copper and zinc. The copper--zinc type has generally been isolated from eukaryotic cells except for the enzyme for the symbiotic marine bacterium Photobacterium leiognathi. The copper--zinc type, from different sources, has a molecular weight of about 32 000, and is composed of two identical subunits, each containing one atom of copper and one atom of zinc. The copper participates in the catalytic activity of the enzyme, while the zinc plays only a structural role. The enzyme has been resolved reversibly. Superoxide dismutases provide protection against oxygen toxicity, against compounds that cause exacerbation of oxygen toxicity, against ionizing radiation, and also against the damaging sequelae of prolonged inflammation. PMID- 6258886 TI - Anaerobic potentiation of copper toxicity and some environmental considerations. AB - The toxicity of copper is substantially greater when the metal ions is applied to cells under conditions of anoxia than under aerobic conditions. The increase in toxicity occurs because Cu(II) is reduced to Cu(I) which is stable under anoxia and is more toxic than the oxidized species. This effect has been observed in mammalian cells in tissue culture and in bacteria. Anoxic potentiation of copper toxicity has also been observed in algal, fungal and yeast cells. The reduction of Cu(II) has been demonstrated by electron paramagnetic resonance spectrometry. The appearance of Cu(I) has been observed by means of specific colorimetric reagent. The reduction of Cu(II) to Cu(I) is not dependent upon concomitant metabolism and requires only a supply of sulphydryl groups. Microorganisms that are responsible for two anaerobic processes of economic importance to humans, the digestion of sewage sludge in effluent treatment plants and the digestion of food in ruminant animals, may be exposed to high concentrations of copper. The environmental consequences of this exposure are discussed. PMID- 6258887 TI - Antihypertensive effects of the novel converting-enzyme inhibitor YS 980 in spontaneously hypertensive rats. PMID- 6258888 TI - Effect of angiotensin converting enzyme inhibition with SQ 14 225 on blood pressure in sheep. AB - The effect of intravenous injection of the angiotensin converting enzyme inhibitor SQ 14 225 on blood pressure, heart rate and plasma renin concentration (PRC) was investigated in 15 intact conscious ewes as follows: sodium replete during angiotensin I infusion (n = 4); sodium replete (n = 6); sodium deplete (n = 5); chronic water deprivation (n = 5); AcTH treated sodium replete (n = 6). Following SQ 14 225 mean arterial pressure fell 5 +/- 1 mmHg in sodium replete, 20 +/- 4 mmHg in acutely sodium deplete, 7 +/- 2 mmHg in chronic water deprivation and 6 +/- 2 mmHg in ACTH treated sodium replete sheep. This suggests that the renin-angiotensin system plays no significant role in maintaining the elevated blood pressure of sheep with ACTH induced hypertension. Heart rate rose in all groups except the water deprived animals following SQ 14 225. PRC rose from 5.1 +/- 2.1 pmo1AI/ml plasma/h. to 12.4 +/- 2.0 in sodium replete sheep, from 11.9 +/- 1.0 to 68 +/- 13 in acutely sodium deficient animals, and from 13.3 +/- 4.3 to 32.9 +/- 0.6 in chronically water deprived animals, but showed little change in ACTH treated sheep, falling from 2.3 +/- 0.5 to 1.7 +/- 0.2 pmo1AI/ml plasma/h. PMID- 6258889 TI - Fibrothecoma of the broad ligament. AB - We present a patient with a primary extraovarian fibrothecoma, an extremely rare lesion originating in the broad ligament. Possible sources of origin and significance are discussed. PMID- 6258890 TI - [Renal tolerance of combined treatment with cefotaxime and gentamicin (author's transl)]. AB - Treatment of 20 patients with 2 g cefotaxime intravenously and 80 mg gentamicin intramuscularly b.i.d. for various reasons before antibiograms were available showed no recognizable influence on renal function after one week. Patients were without renal disease and of both sexes on groups from 19-23, 36-59 and 63-69 years of age. No damage to the kidneys was evident when creatinine clearance, serum creatinine and urea concentrations and the usual urinalysis were considered. PMID- 6258891 TI - [Malignant fibrous histiocytoma after supracondylar femoral fracture (author's transl)]. AB - Supracondylar slanting fracture of the femur was treated by osteosynthesis in a 14-year-old girl. Two months after removal of the plate and screws, 10 months after the initial trauma, a malignant bone tumour in the form of malignant fibrous histiocytoma was diagnosed at the same location after a renewed fracture. The preceding trauma may be assumed to be one of the reasons for occurrence of this rare tumour. PMID- 6258892 TI - [Glomus tumours: morbid-anatomical analysis of 58 cases, especially infiltrated forms (author's transl)]. AB - Analysis of 58 glomus tumours revealed a higher incidence among males. The upper limbs were the most frequent site. The tumour is usually small, lies in subcutaneous tissue, occasionally subungual, and is often very painful. There may be more than one tumour. Most of the tumours are encapsulated and of the angiomatous type. Cases with predominantly vessels of type I (after Masson) correspond to the so-called angiomyoma of Schumacher. This form of the tumour is frequently located in the lower limbs. In three younger patients infiltrating soft-tissue tumours were found in the lower limbs. In all three histological examination revealed non-encapsulated, angiomatous glomus tumour, type angiomyoma. There were no signs of malignancy and no metastases. Even though glomus tumours are classified among the benign tumours, there are non encapsulated, angiomatous forms with a tendency to local infiltration and local recurrences. Clinically they are thus semi-malignant. PMID- 6258893 TI - [Amebiasis]. PMID- 6258894 TI - Effect of endogenous TSH on the in vitro responsiveness and binding of TSH in rat thyroid tissue. AB - These studies examined the effect of deficient endogenous TSH (hypophysectomy) on in vitro TSH responsiveness and binding in rat thyroid tissue. The results showed that thyroid from hypophysectomized rats were hyper-responsive to stimulation of cyclic AMP by TSH while PGE1 stimulation of cyclic AMP was similar in hypophysectomized rats compared to controls. When iodide organification was measured, the TSH and dibutyryl cyclic AMP stimulation in hypophysectomized rats was equivalent to the response of control animals. Binding studies demonstrated there was an increased number of TSH receptors in the thyroid from hypophysectomized rats compared to the control group. The affinity constant was unchanged. The results demonstrate that endogenous TSH appears to inversely regulate the responsiveness and number of TSH receptors in thyroid tissue. The effect of an i.v. injection of TSH on the levels of cyclic AMP and binding characteristics of TSH was also examined. Although cyclic AMP levels were significantly increased after a 10 min in vitro incubation of the lobes from TSH injected rats as an indication of persistently bound TSH, the number of TSH binding sites was the same in the saline the TSH-injected animals. PMID- 6258895 TI - CAMP-dissociation kinetics in hormone-dependent and -independent rat mammary tumor cytosols. AB - Cytosols from 7, 12-dimethylbenz (alpha) anthracene-induced rat mammary tumors which exhibit different hormone-responsiveness were compared with respect to their cAMP-dissociation kinetics. At 22 degree C, pH 4.5, 1 micrometer cAMP, hormone-dependent mammary tumors exhibited monophasic dissociation rates with a rate constant of k-1 = 0.06 min-1. In contrast, hormone-independent mammary tumors exhibited biphasic dissociation curves with rate constants of k-1 = 0.47 and k-2 = 0.06 min-1. The binding of cAMP was completely reversible; radio labeled ligand was completely dissociated by 1mM nonradioactive cAMP; the binding protein could be reassociated to its original binding level after dextran-coated charcoal adsorption. The mammary cytosols exhibited specific binding for cAMP which could be displaced partially by cGMP but not by ATP, ADP, AMP, or adenosine. Receptor inactivation during the course of incubation was negligible. Both mammary tissue cytosols exhibited similar association rates at 22 degree C, pH 4.5, 1 micrometer cAMP (k+1 = 5-7 x 10(5)M-1 min-1). These data indicate that mammary tissues exhibit 2 cAMP dissociation rates. Hormone-dependent mammary tumors exhibit a dissociation constant of a high affinity binding site (k-1/k+1 = 0.07 micrometer) whereas hormone-independent mammary tumors exhibit dissociation constants of one high affinity (k-1/k+1 = 0.07 micrometer) and a second low affinity site (k-1/k+1 = 0.05 micrometer). PMID- 6258897 TI - Evidence for guanosine 3',5'-monophosphate as a putative mediator of insulin secretion from isolated rat islets. PMID- 6258898 TI - Plasma aldosterone and corticosterone responses to adrenocorticotropin, angiotensin, potassium, and stress in spontaneously hypertensive rats. AB - The responses of plasma aldosterone and corticosterone to ACTH, angiotensin II (AII), and potassium chloride (KCl) infusion and the aldosterone, corticosterone and PRA responses to immobilization stress were studied in 2-month-old spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) normotensive controls. Basal levels of plasma aldosterone and corticosterone were greater and PRA was less in the SHR than in the WKY. Aldosterone and corticosterone responses to graded AII were similar in both groups. Aldosterone and corticosterone responses to graded doses of KCl and ACTH, however, were significantly greater in SHR than in WKY normotensive rats. Plasma corticosterone, PRA, and aldosterone responses to immobilization stress were reduced in SHR compared to WKY. At 2 months of age, blood pressure was definitely elevated in SHR and was associated with low PRA and relatively high basal levels of aldosterone and corticosterone. Discordance between the renin-angiotensin system and mineralocorticoid secretion in the SHR may be due to enhanced adrenal sensitivity to factors such as ACTH and potassium. Suppressed PRA in SHR may be due, in part, to increased mineralocorticoid secretion, resulting in sodium retention and intravascular volume expansion. PMID- 6258896 TI - Ovarian gonadotropin-releasing hormone (GnRH) receptors: characterization, distribution, and induction by GnRH. PMID- 6258899 TI - Effects of adrenocorticotropic hormone on low density lipoprotein receptors of human fetal adrenal tissue. AB - In the present investigation, the mechanism(s) whereby ACTH stimulates low density lipoprotein (LDL) metabolism in human fetal adrenal was evaluated. Plasma membrane fractions were prepared from fetal adrenal tissue fragments incubated in lipoprotein-poor serum with or without ACTH, and the binding of [125I]iodo-LDL to such membrane fractions was examined. The mean specific binding capacity for [125I]iodo-LDL by membrane fractions prepared from four separate fresh human fetal adrenal glands was 1370 +/- 168 ng mg-1 protein (mean +/- SE), and the concentration of [125I]iodo-LDL producing half-maximal binding was 20.8 +/- 1.2 ng ml-1. Thus, the presence of high affinity, low capacity binding sites for LDL in human fetal adrenal tissue was confirmed. When human fetal adrenal tissue was maintained in organ culture for 2 days in medium containing lipoprotein-poor serum in the absence of ACTH, and plasma membrane fractions were subsequently prepared, the binding capacity for LDL in such membrane fractions was the same as or slightly greater than that in membrane fractions prepared from fresh tissue. When ACTH was present in the culture medium, the binding capacity for LDL was doubled compared to that in membrane fractions prepared from tissues incubated in the absence of ACTH. The rate of [125I]iodo-LDL degradation by human fetal adrenal tissue maintained in medium containing ACTH was also twice that of tissue maintained in the absence of ACTH. These results demonstrate that ACTH causes an increase in the number of LDL-binding sites in human fetal adrenal tissue in vitro. This is one mechanism whereby ACTH stimulates LDL metabolism in this tissue. PMID- 6258900 TI - A23187 inhibits adrenal protein synthesis and the effects of adrenocorticotropin (ACTH) on steroidogenesis and phospholipid metabolism in rat adrenal cells in vitro: further evidence implicating phospholipids in the steroidogenic action of ACTH. AB - We examined the effects of ACTH and the Ca++ ionophore, A23187, on steroidogenesis and phospholipid metabolism during incubation of dispersed rat adrenal cells. Increasing doses of ACTH elicited nearly parallel increases in corticosterone production and adrenal inositide (mono- and di-) concentrations. As reported previously by other investigators in Y1 cells, A23187 inhibited ACTH- and cAMP-stimulated, but not basal or pregnenolone-stimulated, corticosterone production. A23187 also inhibited ACTH-induced increases in phosphatidic acid, phosphatidylinositol, and diphosphoinositide, and this was attended by inhibition of [3H]leucine incorporation into protein. These findings support our previous contentions that: 1) a labile protein is required for ACTH-induced increases in adrenal phospholipids in the phosphatidate-polyphosphoinositide polyglycerophospholipid pathway; and 2) these phospholipids are involved in the steroidogenic action of ACTH. PMID- 6258902 TI - Role of alpha-adrenergic mechanism in regulating tonic luteinizing hormone release in conscious ovariectomized rats. AB - The role of brain catecholamines in controlling tonic LH secretion was studied in unanesthesized, freely moving, ovariectomized rats. Pretreatment with reserpine (10 mg/kg), given 24 h before the experiment, significantly suppressed pulsatile LH secretion in these rats. Intraperitoneal administration of clonidine (1 mg/kg), an alpha-adrenergic stimulating agent, significantly raised plasma LH levels in reserpine-treated rats. On the other hand, the administration of apomorphine (1.5 mg/kg), a dopamine receptor-stimulating agent, had no effect on the plasma LH levels. These findings suggest an excitatory role of noradrenaline, operating through alpha-adrenergic receptors, in pulsatile LH secretion in ovariectomized rats. PMID- 6258901 TI - Role of the liver in regulating somatomedin activity: effects of streptozotocin diabetes and starvation on the synthesis and release of insulin-like growth factor and its carrier protein by the isolated perfused rat liver. PMID- 6258903 TI - Thyroid hormone regulation of beta-adrenergic receptor number in aging rats. AB - To evaluate the capacity of the myocardium in aged rats to respond to hyperthyroidism, we quantified myocardial beta-adrenergic receptors in female Fischer 344 rats of 3, 12, and 24 months of age. In T3-treated rats (500 microgram T3/kg . day for 3 days), myocardial beta-adrenergic receptors, as measured by [3H]dihydroalprenolol binding, were significantly increased (P less than 0.01) over controls in 3-, 12-, and 24-month-old animals. The data demonstrate that senescent rats retain the capacity to increase myocardial beta adrenergic receptors in response to exogenous hyperthyroidism. In the myocardium, the mechanism of decreased catecholamine responsiveness in aging appears to be at other than the beta-adrenergic receptor site, since receptor density is unaltered with age, as is receptor modulation in response to hyperthyroidism. PMID- 6258904 TI - Follicle-stimulating hormone induction of luteinizing hormone receptor in cultured rat granulosa cells: an examination of the need for steroids in the induction process. AB - The induction of LH receptors by FSH in cultured rat granulosa cells and the effects of ovarian steroids on this process were examined. Granulosa cells were isolated from the ovaries of untreated immature rats (25 days old) and cultured with highly purified FSH (Sairam; 250 ng/ml). After culture (48-96 h in chemically defined media), both the binding of [125I]hCG and the responsiveness (cAMP and progesterone production) to an acute LH stimulus (100 ng/ml; NIH B8) were measured. The appearance of LH/hCG-binding sites and LH responsiveness indicates the presence of functional LH receptors. The induction of LH receptors by FSH requires a lag period of 24-48 h. After 48 h, the concentration of LH receptors in cultured granulosa cells continues to increase with time in culture with FSH; the continuous presence of FSH is required to maintain the induction process. If granulosa cells are cultured without hormone for 24-48 h before FSH is added, no induction of LH receptors occurs. However, if 17 beta-estradiol (5 X 10(-7) M) is added during this initial period, then the cells are responsive to the later addition of FSH. This maintenance of FSH responsiveness is not observed when dihydrotestosterone or progesterone is substituted for 17 beta-estradiol in the initial culture period. The FSH-dependent induction of LH receptors in cultured rat granulosa cells can be blocked if an inhibitor of steroidogenesis, such as aminoglutethimide phosphate (AGP; 1 mM), is added along with FSH at the initiation of the culture. The inclusion of progesterone, dihydrotestosterone, or 17 beta-estradiol (but not 20 alpha-dihydroprogesterone) in the culture together with FSH and AGP will overcome the inhibition by AGP and restore the induction of LH receptors. The results suggest that steroids produced by the developing follicle can modulate the FSH-dependent induction of LH receptors, and this may play a role in the development of follicular responsiveness to LH. PMID- 6258905 TI - Decreased brain serotonin turnover after short term (two-hour) adrenalectomy in rats: a comparison of four turnover methods. AB - Within the first 2 h after adrenalectomy in rats there is a marked decrease in hypothalamic, brain stem, and hippocampal serotonin (5HT) turnover. This adrenalectomy-induced decrease in brain 5HT turnover was demonstrated in this study using four different methods. These include 1) accumulation of 5HT after monoamine oxidase inhibition with pargyline, 2) decline of 5-hydroxyindoleacetic acid after pargyline, 3) accumulation of 5-hydroxytryptophan after aromatic L amino acid decarboxylase inhibition with m-hydroxybenzylhydrazine, and 4) accumulation of 5-hydroxyindoleacetic acid after probenecid. The adrenalectomy induced decreases in 5HT turnover in these areas were prevented by glucocorticoid treatment with either corticosterone or dexamethasone. The similarity of the results obtained with four different methods of assessment of brain 5HT turnover provides strong evidence to suggest that the activity of 5HT neurons, in at least three brain areas, is decreased within the first 2 h after adrenalectomy. Also, it seems likely that glucocorticoid withdrawal is the important factor in this adrenalectomy-induced decrease in brain 5HT turnover. In addition, an increase in hypothalamic 5HT turnover in response to the surgical stress of sham adrenalectomy could be demonstrated. The adrenalectomy-induced decreases in brain 5HT turnover were also prevented by the administration of the serotonin receptor antagonist, pizotifen. In addition, serotonin receptor blockade with pizotifen inhibited the effect of corticosterone to normalize the adrenalectomy-induced changes in both the plasma ACTH concentration and brain 5HT turnover. These data provide further support for an interaction between glucocorticoids and brain 5HT neurons. PMID- 6258906 TI - Steroid-metabolizing enzymes in human breast cancer cells. II. 5 alpha-Reductase, 3 alpha-hydroxysteroid oxidoreductase, and 17 beta-hydroxysteroid oxidoreductase. AB - Evidence that some human breast cancers can form biologically active sex steroids from extracellular precursors has prompted us to investigate several human breast cancer cell lines for similar steroidogenic capability. We have previously reported that MCF-7 and MDA-MB-231 human breast cancer cells can transform testosterone to estradiol but that aromatase activity is not apparent in the HBL 100 human breast cell line. We report here the presence of 17 beta-hydroxysteroid oxidoreductase, 5 alpha-reductase, and 3 alpha-hydroxysteroid oxidoreductase activities in all three cell lines. Characterization of these enzymes in MCF-7 cells indicated that the intracellular location, temperature and pH optima, cofactor requirements, and apparent substrate affinities for each are generally similar to those described in several other mammalian systems. The presence of 17 hydroxysteroid oxidoreductase, aromatase, 5 alpha-reductase, and 3-hydroxysteroid oxidoreductase activities in MCF-7 suggests the possibility that the hormonal regulation of these human breast cancer cells may be mediated in part by intracellular estrogen and/or androgen biosynthesis. PMID- 6258907 TI - Control of release of adrenocorticotropin and vasopressin by the supraoptic and paraventricular nuclei. AB - To determine the relative roles of the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei in the control of the release of vasopressin and of ACTH, we have examined the hormonal responses to electrical stimulation (200 microA, 0.2 msec, 100 Hz, 20 sec) of these regions. Cats were anesthetized with chloralose-urethane. Blood samples were taken 30 sec before stimulation and 1.5 min poststimulation. ACTH and vasopressin were measured by RIA. Electrical stimulation of the caudal pole of the SON increased vasopressin in plasma (1.82 +/- 0.41 microU/ml, n = 17, P less than 0.01) and decreased ACTH (-26 +/- 4 pg/ml, n = 13, P less than 0.01). In contrast, stimulation of the PVN increased vasopressin (2.01 +/- 0.60 microU/ml, n = 7, P less than 0.001) and increased ACTH (107 +/- 20 pg/ml, n = 32, P less than 0.01). Previous work has shown that vasopressinergic neurons of PVN, but not of SON, project to the zona externa of the median eminence. Other have suggested that the retrograde flow of blood from the neural lobe to the median eminence and thence to the anterior lobe would allow vasopressin to influence the release of ACTH. The present results indicate that both SON and PVN facilitate the release of vasopressin. However, PVN facilitates, but SON inhibits the release of ACTH. These findings suggest that the projection from PVN to the zona externa of the median eminence mediates the release of ACTH and that retrograde flow from the neural lobe is not important in the control of ACTH release during modest and transient increases in the release of vasopressin. PMID- 6258909 TI - Porcine granulosa cells in suspension culture. I. follicle-stimulating hormone induction of human chorionic gonadotropin-binding sites on cells from small follicles. AB - Granulosa cells were aspirated from small follicles from the ovaries of 3- to 6 month-old pigs, washed, and cultured in sealed spinner flasks. Medium 199 was supplemented with 10% fetal bovine serum, insulin, dexamethasone, T4, and antibiotics. FSH, LH, or hCG was added daily where appropriate. Cultures were sampled every other day for 10 days. Cells were examined microscopically, and cellular [125I]hCG binding and DNA content were measured. The cells aggregated and underwent morphological luteinization within 4 days in the absence or presence of FSH, LH, or hCG. Aggregation in culture was independent of clumping at the time of harvest. There was no measurable cell proliferation, based on the lack of mitotic figures and the lack of any increase in DNA. The average yield of luteinized cells from small follicle granulosa cells was 7% at 6 days. Cell concentration remained constant between days 6-10. Between days 0-2, [125I]iodo hCG binding declined in all cultures. It continued to decline through day 10 in control cultures. In cultures containing FSH, binding increased to a maximum on day 6. The effect was specific for FSH. Increased binding was due to increased numbers of binding sites per cell. Equilibrium saturation binding data indicated that [125I]iodo-hCG binding to freshly harvested and cultured granulosa cells was specific, saturable, and of high affinity. The numbers of binding sites were 938 +/- 49 and 7602 +/- 156 sites/cell for control and FSH on day 6, respectively, compared to 498 +/- 14 sites/cell on day 0. The effect of FSH on the increase in binding sites was specific and dose related. Autoradiographic studies indicated a skewed normal frequency distribution of [125I]iodo-hCG-binding sites on cultured cells PMID- 6258908 TI - Androgen control of an inhibitory modulator of phosphodiesterase in rat epididymis and prostate. AB - When rats were injected with the progestin ethynodiol diacetate in doses that suppressed spermatogenesis and the growth of accessory sex glands, the level of phosphodiesterase in epididymal and prostate tissues increased 5- to 10-fold. This increase was prevented by concurrent administration of testosterone propionate. A similar increase in phosphodiesterase activity was observed in the epididymides and prostates of castrated animals, with reversal by treatment with androgen. In immature rats approaching puberty, the phosphodiesterase activity in epididymis and prostate increased while the blood testosterone level remained low; as the testosterone level rose with the onset of puberty, the phosphodiesterase activity decreased. Incubation of enzymically active extracts of accessory tissues from castrated rats with heat-treated extracts of the corresponding normal tissues resulted in strong inhibition of the initially high phosphodiesterase activity. The addition of heat-treated extracts of accessory glands from castrated rats to enzymically active extracts of the corresponding tissues from normal rats resulted in a marked elevation of their phosphodiesterase activities. Of the two heat-stable modulators, the inhibitor factor was dialyzable. The dependence of this factor on testosterone suggests a mechanism of action by which the steroid hormone, by inducing the production in its target tissues of an inhibitory modulator of phosphodiesterase, controls the maintenance of functional levels of cAMP. PMID- 6258910 TI - Binding characteristics of a biologically active variant of human growth hormone (20K) to growth hormone and lactogen receptors. AB - The dose-dependent displacement characteristics of a biologically active 20,000 molecular weight human pituitary growth hormone variant (20K) and of human growth hormone (hGH) were compared using hGH liver plasma membrane receptors both from 20-30 day pregnant rabbits and from normal female rats and also using mammary gland plasma membrane receptors from 5-6 day lactating rabbits. Different preparations of 20K were found to be only 3-20% as potent as hGH when compared at the dose necessary to cause 50% displacement of (125I)iodo-hGH from liver receptor and was 22-53% as effective as hGH in the mammary receptor assay system. These findings suggest that 20K and hGH may have separate receptors or that the binding characteristics of the two hormones may be quite different. PMID- 6258911 TI - Na+ + K+-ATPase in serially excised segments of epileptic monkey cortex. AB - The membrane-bound enzyme Na+ + K+-ATPase was measured in serially excised specimens of cerebral cortex in epileptic and control monkeys. Experimental chronic epileptic cortex showed significantly lower values than controls, as is seen in some other models and human epilepsy, but is different from the increased enzyme values in cobalt and freezing lesion epilepsy. PMID- 6258912 TI - Adenylate kinase isoenzyme patterns in normal and neoplastic human lung, and in various adult as compared to fetal rat tissues. AB - The isozyme pattern and total activity of adenylate kinase were studied in normal adult and fetal human and rat tissues using starch gel electrophoresis. Three adenylate kinase isoenzymes were identified in human tissues. Although normal adult lung exhibited higher adenylate kinase activity than did its fetal or neoplastic variant, isozyme patterns in the three types of tissues were indistinguishable from each other and from that in fetal human liver. The pattern of these three isozymes in rat lung (as in spleen) also did not change between fetal and adult life. However, adult kidney and heart of this species did appear to contain isozymes not present in fetal life. Brain (both adult and fetal) was striking different from all the other tissues in that it contained only one adenylate kinase isozyme. The total adenylate kinase activity per gram of adult rat liver, kidney and lung was significantly higher than in the cognate fetal organs, whereas that in brain or spleen did not change with age. The activity in adult heart (similar to the fetal one) was higher than in any other tissue examined. PMID- 6258913 TI - Effect of sodium deoxycholate on intestinal glucose absorption and (Na+-K+) atpase in the rat. AB - The effects of deoxycholate on glucose transport and intestinal (Na+-K+)-ATPase activity have been investigated in the rat jejunum in vivo using a perfusion technique. PMID- 6258914 TI - Diagnostic significance of connective tissue enzymes. AB - In spite of the extensive literature, little is known of the diagnostic value of the enzymes of connective tissue metabolism. This review summarizes the available information and assesses the significance of enzyme measurements for the diagnosis of hereditary and nonhereditary connective tissue diseases, with emphasis being given to the roles of abnormal activities of collagenases and lysosomal glycosidases in the detection of fibrotic processes. PMID- 6258915 TI - Characterization of purine nucleotide metabolism in cultured fibroblasts with deficiency of hypoxanthine-guanine phosphoribosyltransferase and with superactivity of phosphoribosylpyrophosphate synthetase. AB - Cultured fibroblasts with hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency exhibited acceleration of purine synthesis de novo, absence of salvage IMP synthesis from hypoxanthine, but normal total IMP synthesis. Cells with phosphoribosylpyrophosphate synthetase superactivity exhibited acceleration of both de novo and salvage IMP synthesis and increased total IMP synthesis. The study of mutant cells furnished evidence that in normal as well as mutant cells, GMP and AMP are not converted to each other in significant amounts and that these nucleotides are not degraded by nucleotidases. Purine nucleotide degradation in fibroblasts occurs mainly by dephosphorylation of IMP. In HGPRT-containing cells, salvage IMP synthesis from preformed and exogenously supplied hypoxanthine is the main source for IMP production. PMID- 6258917 TI - The electrochemical proton gradient generated by the fumarate-reductase system in Escherichia coli and its bioenergetic implications. AB - Proton translocation, coupled to electron transfer in the fumarate reductase system, generates and electrochemical potential gradient for protons (delta approximately mu H+). The magnitude of this free energy gradient has been determined in the Escherichia coli strains ML 208-225 and AN 283. The measurements were performed in (inverted) membrane particles, right-side out membrane vesicles and EDTA-treated intact cells in external media of various ionic compositions and pH. The maximal values of delta approximately mu H+ in these three systems were +103, -101 and -105 mV, respectively. This implicates that in E. coli, upon transition from oxygen to fumarate as electron acceptor, the magnitude of the delta approximately mu H+ decreases considerably. This change of delta approximately mu H+ has substantial consequences for the cellular metabolism. PMID- 6258916 TI - Receptor-specific large-scale purification of cholera toxin on silica beads derivatized with lysoGM1 ganglioside. AB - 1. A receptor-specific affinity chromatographic method for large-scale purification of cholera toxin is described. The receptor ganglioside for cholera toxin, GM1, is hydrolysed to lysoGM1 which is then covalently coupled, via stabilized Schiff's bases, to porous silica beads (Spherosil) onto which a layer of DEAE-dextran has been adsorbed and cross-linked before coupling. Columns of these Spherosil-DEAE-dextran-lysoGM1 beads, in contrast to particles derivatized with lysoGA1, bound the cholera toxin of Vibrio cholerae culture filtrates, after which the toxin could be eluted with the aid of an acid citrate buffer (pH 2.8). 2. The toxin-binding capacity was directly proportional to the amount of lysoGM1 in the column: 2.3 mg/mu mol lysoGM1. The yield of purified toxin after acid elution and pH neutralization was essentially quantitative (83-107%). 3. The affinity-purified toxin contained less than 5% impurities, but consisted of a mixture of predominantly intact holotoxin and B subunit protomer which could readily be separated by gel filtration on Sephadex G-100. 4. Scaling up of the technique was possible: a 1 kg column enabled us to treat 1000-1 cultures of V. cholerae and thus to isolate 20 g of cholera toxin per cycle. PMID- 6258919 TI - Fractionation of the detergent-resistant filamentous network of Ehrlich ascites tumour cells. AB - Previous investigations of the filamentous network in eukaryotic cells have been based on observations by electron and fluorescence microscopy. In order to examined, in more detail, the interconnection of the various components of th filamentous network, we have treated Ehrlich ascites tumour cells with Triton X 100 in the presence of Mg++, disassembled the detergent-resistant, residual cell structure with Tris-EDTA and subjected the postnuclear supernatant to sucrose density gradient equilibrium centrifugation. Using this technique we are able to demonstrate 1) the association of the major part of intermediate-sized filament protein (vimentin) with unfolded ribosomal subunits, 2) the nearly identical sedimentation behavior of the boundary lamina and actin, and a minor part of the intermediate-sized filament protein respectively, and 3) the association of a Ca++-dependent protease specific for vimentin intermediate-sized filament protein with the Triton X-100 resistant, residual cell structure. Furthermore, we are able to confirm, by labelling intact Ehrlich ascites tumour cells with [3H] concanavalin A and recovering radioactivity in the lighter sucrose gradient fractions, that the detergent-resistant boundary lamina is derived from the plasma membrane. The presence of coated vesicles in Triton X-100-treated cells as well as of coated pits in the derived membrane point at the same origin of the boundary lamina. The results of the fractionation study are correlated with structures observed by electron microscopy of ultrathin sections of the intact filamentous network. PMID- 6258918 TI - Inhibition of the links between electron transfer and proton translocation in mitochondria. AB - The mechanism by which proton extrusion is linked to electron transfer in mitochondria was investigated by means of the primary amine-specific reagent fluorescamine, and of compounds obtained from the reaction of fluorescamine with simple amines (e.g. benzylamine) and with the mycosamine-containing antibiotic amphotericin B. The effect of these 'modifiers' (i.e. fluorescamine transfer chain were assayed separately using specific inhibitors to block the action associated with the other site. Both types of modifiers inhibited the proton extrusion across the membrane to a significantly greater extent than the electron transfer process in both sites II and III. In contrast, the lactone derivative (or cyclic form) of the amine-fluorescamine compounds had no significant inhibitory effect on the proton extrusion and its associated electron transfer. These results are consistent with the hypothesis that the link between proton extrusion and electron transfer in mitochondria is indirect in nature. The results show that: (a) the links involved in sites II and III are identical or very similar in nature; (b) a covalent modification of primary amino groups in the inner membrane is not essential for the expression of these differential inhibitory effects; (c) specific structural features in the amine-fluorescamine compounds, and in the mitochondria-fluorescamine derivatives, are crucial for the expression of the inhibitory effects. Our results contradict the 'redox loop' model of Mitchell, and are compatible with the proton pump concept for the linked proton translocation in oxidative phosphorylation. PMID- 6258920 TI - Distinctive features of dinoflagellate chromatin. Absence of nucleosomes in a primitive species Prorocentrum micans E. AB - The absence of nucleosome-like structures from purified nuclei of the primitive dinoflagellate Prorocentrum micans was demonstrated by three means. i) Electron microscopy revealed mostly thin, smooth 6-nm nucleofilaments in chromatin incubated at various ionic strengths and either fixed in 0.1% glutaraldehyde or unfixed. No "beads-on-a-string" structure was found. ii) Analysis of nuclear proteins showed that low amounts of basic proteins were present (basis proteins: DNA less than 0.1), the two major one with molecular weights 12 000 and 13 000 and that histones characteristic of eucaryotes were absent. iii) Digestion of the nuclei with micrococcal endonuclease of DNase I did not result in partially digested DNA fragment repeats. Only about 10% of the bulk of the nuclear DNA was digested by micrococcal endonuclease. The high molecular weight of the remainder suggests particular protection against this type of nuclease. In the light of these distinctive nuclear features, we discuss the evolutionary position of the dinoflagellate protists with respect to the procaryotes and eucaryotes. PMID- 6258921 TI - Choroid plexus localization of 99mTc-pertechnetate. AB - Autoradiograms were performed on brain slices, 3 h after 99mTc-pertechnetate injection, and 24 h after previous treatment with stannous pyrophosphate. On macroautoradiograms, the radioactivity was focused entirely upon plexus areas. Silver grains were predominantly overlying the cytosol of brush border cells; less than 10% of the total plexus radioactivity was found in vascular structures. These findings suggest that a possible metabolic phenomenon exists rather than a passive distribution. PMID- 6258922 TI - 75Se selenomethionine in the diagnosis of hepatocellular carcinoma. Report of a false positive scan. AB - A 74 year old man presented with cryptogenic liver cirrhosis and ascites. On 99Tcm sulphur colloid scanning he was found to have a filling defect in the right lobe of the liver which disappeared when the liver scan was repeated with 75Se selenomethionine. This lesion, initially thought to be a hepatoma, proved eventually at post mortem to be a hyperplastic hepatic nodule. PMID- 6258923 TI - The histoenzymological pattern of human breast carcinoma. PMID- 6258924 TI - Biochemical comparison of HLA-DR molecules derived from autologous human T and B lymphoblasts. AB - Earlier findings that human activated T blasts display HLA-DR determinants have been confirmed. After phytohemagglutinin activation, Percoll gradient-purified blast cells were cultured for two weeks in mitogen-derived supernatants from human lymphocyte cultures. Using purified T blasts and internal labeling procedures, it was established that T blasts actively produced HLA-DR-like chains, as assessed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Further, HLA-DR chains obtained from Epstein-Barr virus-transformed B cells and from T blasts of the same donor were compared. Two-dimensional gel electrophoretic comparisons indicated a striking homology between 29 kD and 35kD chains, obtained from the two different cell types. Peptide map analysis and preliminary amino acid sequence comparisons further supported this similarity. A more complete analysis would, however, be required to prove actual identity. The fact that human T blasts produce and display HLA-DR molecules very similar, if not identical, to those present on B cells must then be incorporated into models discussing major histocompatibility complex-restricted collaborations involving HLA-DR molecules. PMID- 6258925 TI - Elicitation of primary anti-Sendai virus cytotoxic T lymphocytes with purified viral glycoproteins. AB - The requirement of integration of viral proteins into cell surface membranes of host cells for elicitation of anti-Sendai virus (SV) cytotoxic T lymphocytes (CTL) has been investigated. The purified hemagglutinin-neuraminidase (HN) and fusion (F) glycoproteins of SV incorporated into phospholipid vesicles was used to analyze this question. Phospholipid vesicles possessing an active HN and F glycoprotein were capable of eliciting both anti-SV CTL and antibodies. However, the incorporation of an inactive F glycoprotein into HN-containing vesicles or its absence from such vesicles resulted in stimulation of only anti-SV antibodies and not anti-SV CTL. PMID- 6258926 TI - Influence of thyrotropin releasing hormone and histidyl-proline diketopiperazine on spontaneous locomotor activity and analgesia induced by delta 9 tetrahydrocannabinol in the mouse. AB - The influence of thyrotropin releasing hormone (TRH) and its postulated metabolite histidyl-proline diketopiperazine (HPD) on sedation and analgesia produced by delta 9-tetrahydrocannabinol (THC) was investigated in mice. Intracerebral administration of HPD (10 microgram) by itself decreased motor activity, whereas, TRH (10 microgram) was without any effect. THC (10 and 20 mg/kg) given i.p. decreased the motor activity and this effect was antagonised by prior treatment with TRH or HPD. Administration of THC produced analgesia as evidenced by delay in the tail-flick reaction time to a thermal stimulus. Pretreatment with TRH or HPD also antagonized the THC-induced analgesia. THC induced analgesia was not modified by s.c. pretreatment with naloxone, an opiate antagonist. TRH or HPD pretreatment had no effect on the distribution of total radioactivity representing THC and its metabolites in brain and plasma. These studies indicate that TRH and HPD can antagonize THC-induced sedation and analgesia and that HPD may be an active metabolite of TRH. These effects were observed without altering the distribution of the drug and metabolite in brain and plasma, and therefore their effect may involve their direct actions on the central nervous system. Finally THC induced analgesia does not seem to involve opiate receptors and their involvement in the mechanism by which TRH or HPD antagonize THC-induced analgesia is unlikely. PMID- 6258927 TI - Localization of naloxone-sensitive [3H]dihydromorphine binding sites within the hippocampus of the rat. AB - In vitro radioautographic experiments were performed on coronal rat brain slices to determine the precise localization of [3H]dihydromorphine binding sites sensitive to naloxone, within the hippocampus. Binding was observed in all cell fields and in dentate gyrus (DG) in the order CA2 greater than CA1 greater than CA3 greater than DG. Within each cell field the density of receptors was greatest in the stratum pyramidale, which in field CA2 was 77% as dense as the striatum. The existence of a dense population of opiate binding sites within the hippocampus is consistent with the view that this structure is involved in opiate actions. PMID- 6258928 TI - Opiate and peptide interaction: effect of enkephalins on morphine analgesia. AB - Interactions between the weakly analgesic enkephalins and morphine on morphine induced analgesia were studied. Met-enkephalin exhibited morphine analgesia whereas Leu-enkephalin potentiated it. Both Met- and Leu-enkephalin, when tested alone, were not analgesic. The strongly analgesic FK33824 (Sandoz) compound, like Leu-enkephalin, also potentiated morphine analgesia. Tolerance developed to morphine analgesia but not to Met-enkephalin inhibition of morphine analgesia. PMID- 6258929 TI - Ontogeny of mammalian cardiac alpha 1-adrenergic receptors. AB - We find a similar number of alpha 1-adrenergic receptors in fetal mouse hearts of 15--20 day gestational age as compared to adult mouse hearts, and a significantly greater number of alpha 1-adrenoceptors in the early neonate (7--21 days) hearts. Cardiac norepinephrine (NE) concentrations were extremely low in the fetus and increased continuously after birth to reach adult levels at about 21 days of age. The cardiac alpha 1-adrenergic receptors mature prior to the development of a presynaptic component (NE) and show a dramatic increase in density without a change in affinity in the early neonate which then decreases with innervation. PMID- 6258930 TI - The albino locus produces abnormal responses to opiates in the mouse. AB - Pedigreed inbred lines of pigmented mice were compared with albino lines differing at either a single locus or by a chromosomal segment of interest, for their responses to morphine. In either of two tests, behavioral activation or reduction in core temperature, albino mice were aberrant in their responses, demonstrating reliably less sensitivity to morphine than closely related pigmented lines. These findings suggest the need for caution in the use of albino lines in opiate research. PMID- 6258931 TI - Met-enkephalin[Arg6,Phe7] interacts with the kappa-receptors on guinea-pig ileum. PMID- 6258933 TI - Evidence that vasopressin is involved in the isoprenaline-induced beta-endorphin release. AB - We investigated in conscious rats, whether vasopressin, whose release was stimulated by isoprenaline (i.m.), caused the simultaneous increase in plasma beta-endorphin-like immunoreactivity (beta-EI). The increase in plasma beta-EI following isoprenaline administration was diminished by about 50% in rats pretreated with a vasopressin antagonist and also in rats with a hereditary absolute lack of vasopressin. We conclude that the isoprenaline-induced release of beta-EI is mediated in part by vasopressin. PMID- 6258934 TI - Captopril given intracerebroventricularly, subcutaneously or by gavage inhibits angiotensin-converting enzyme activity in the rat brain. AB - In rats with permanent brain cannulas intracerebroventricular (i.c.v.) injections of 2 microgram captopril nearly abolished drinking responses elicited by i.c.v. injections of 1 mUnit hog renin, 10 pmol synthetic renin substrate or 10 pmol angiotensin I but did not reduce drinking elicited by 10 pmol angiotensin II. Inhibition of the response to precursors of angiotensin II was long-lasting (at least 2 h) and dose-dependent (20 ng-2 microgram captopril). Captopril was 3-5 times more potent than SQ 20,881 i.c.v. Subcutaneous injections of captopril in doses 0.1 to 1.0 mg/kg reduced pressor responses to intravenous injections of angiotensin I without attenuating drinking elicited by i.c.v. injections of angiotensin precursors. Higher doses of captopril, however, given subcutaneously (5-50 mg/kg) or by gavage (10 mg/kg) did not reduce drinking to i.c.v. injections of renin or angiotensin I (but not angiotensin II). We conclude that captopril inhibits angiotensin-converting enzyme activity in the brain even when given subcutaneously or by gavage in doses commonly used in the rat. PMID- 6258932 TI - The effects of acute and chronic morphine administration on GABA receptor binding. AB - The effect of acute and chronic morphine administration and naloxone-precipitated withdrawal on the binding of [3H]GABA to its receptor sites in rat brain membranes was investigated. Acute morphine (25 mg/kg) administration produced a decrease in the GABA binding in cerebellum, cortex and striatum. This decrease appears to be due to a selective decrease in the number of high-affinity GABA receptor binding sites. In contrast, rats chronically treated with morphine by pellet implantation did not exhibit any changes in GABA receptor binding, except for an increase in pons medulla. However, in rats which were physically dependent, as indicated by naloxone-precipitated withdrawal, GABA binding was decreased significantly in cerebellum and striatum, relative to chronic morphine treatment or placebo pellet controls. This decrease was due to a decrease in the number of low affinity GABA receptor binding sites. Both chronic morphine and naloxone-precipitated withdrawal treatments produced an increase in GABA binding in the pons medulla. These results suggest that morphine may produce some of its effects by modulating GABAergic systems and that high and low affinity GABA receptor sites may play a differential role during various morphine treatments. PMID- 6258936 TI - Inhibition of intestinal secretion without reduction of cyclic AMP levels. AB - Net water transport by the jejunum of anaesthetized rats was measured together with jejunal cyclic AMP content. Vasoactive intestinal peptide stimulated secretion and elevated the cyclic AMP level. Morphine (10 mg/kg s.c.) inhibited the stimulated secretion but failed to depress the cyclic AMP accumulation. It is suggested that cyclic AMP may not be the mediator of intestinal fluid secretion. Alternatively, morphine may block the secretory effect of cyclic AMP elevated by vasoactive intestinal peptide. PMID- 6258935 TI - Inhibitory action of adenosine on synaptic transmission in the hippocampus of the guinea pig in vitro. AB - Thin hippocampal slices were prepared from guinea pig brains. the postsynaptic field potential elicited in the pyramidal cell layer of CA3 region by mossy fiber stimulation was reversibly inhibited by application of adenosine to the perfusion medium. Among purine and pyrimidine derivatives, only adenosine and adenine nucleotides depressed the field potential with similar dose-response curves at concentrations of 10(-5).10(-3) M. In order to elucidate the mechanism of the inhibitory action of these agents, the effects of adenosine and adenine nucleotides on membrane events in pyramidal neurons were studied using intracellular recording techniques. Application of adenosine and adenine nucleotides hyperpolarized membrane potential and markedly depressed the EPSPs (excitatory postsynaptic potentials) elicited in the pyramidal cell by granular cell activation. However the spike generating mechanism of the neuron was not interfered with and membrane conductance was not increased by adenosine and adenine nucleotides. 4-Aminopyridine counteracted the inhibitory action of adenosine. These findings indicate that the mechanism of the inhibitory action of adenosine and adenine nucleotides is different from that of conventional inhibitory neurotransmitters such as gamma-aminobutyric acid and suggest a presynaptic action of adenosine and adenine nucleotides. PMID- 6258937 TI - Cyclic nucleotide changes in aortic segments derived from hypertensive rabbits. AB - Mean blood pressure increase was produced by: (1) renal constriction plus contralateral nephrectomy, and (2) cadmium acetate ingestion. Blood pressure was measured directly via the middle ear artery. Cyclic nucleotide levels were determined by 125I-radioimmunoassay. Levels of cAMP were reduced in both hypertensive subgroups when compared to controls. The altered cAMP levels suggest a relationship of this nucleotide to the maintenance of increased blood pressure. PMID- 6258938 TI - Ethyl beta-carboline-3-carboxylate antagonises the effect of diazepam on a functional GABA receptor. PMID- 6258939 TI - Presynaptic inhibition of vascular sympathetic neurotransmission by adenosine. AB - Infusion of adenosine (1 mg/kg/min i.v.) to pentobarbital-anesthetized dogs resulted in a decrease in blood pressure and significant attenuation of the femoral vasoconstrictor responses to lumbar sympathetic nerve stimulation. The vasoconstrictor action of exogenous norepinephrine was unaltered during adenosine infusion. The inhibitory action of adenosine on responses to sympathetic nerve stimulation could be antagonized by theophylline (5 mg/kg i.v.), but not indomethacin (10 mg/kg i.v.). Additional experiments were performed to study the role of this sympathoinhibitory action of adenosine in the vasodilator effect of the compound. Intraarterial administration of adenosine produced dose related femoral vasodilatation. Sympathetic denervation of the femoral vascular bed did not alter the vasodilatory action of adenosine. Continuous lumbar sympathetic nerve stimulation or intraarterial norepinephrine infusion also did not change the vasodilatation produced by adenosine. The vasodilatory action of adenosine was antagonized by theophylline. These results suggest that adenosine causes inhibition of sympathetic neurotransmission to the femoral vasculature via an action on presynaptic purinergic receptors. However, this presynaptic inhibitory action of adenosine is not involved in the femoral vasodilatation produced by the compound. PMID- 6258940 TI - Tricyclic antidepressant drug treatment decreases alpha 2-adrenoreceptors on human platelet membranes. PMID- 6258942 TI - Induction of analgesia by central administration of ORG 2766, an analog of ACTH4- 9. AB - Dose-dependent analgesia was produced by microinjection of ORG 2766 into the periaqueductal gray (PAG). This analgesia was found to be potent and long-lasting and occurred at doses which were equimolar to those necessary for morphine analgesia. The same doses failed to produce analgesia by the cerebroventricular route, suggesting that the PAG was the site of action of this effect. Naloxone failed to reduce the analgesia and morphine tolerant did not diminish the effect significantly. Additionally, ORG 2766 at concentrations up to 10 micrometer failed to inhibit binding of [3H]naloxone to brain opiate receptors in vitro. These results suggest a non-opiate mechanism of action and are discussed in terms of a proposed alpha-MSH or ACTH receptor. PMID- 6258941 TI - d-Propoxyphene acts differently from morphine on opioid receptor-effector mechanisms. AB - The actions of d-propoxyphene and morphine on opioid receptor mechanisms were compared. In assay measuring receptor binding selectivity in vitro, with dihydromorphine, naloxone and an enkephalin analogue as radioactive ligands, d propoxyphene differed from morphine in having a higher relative affinity for sites occupied by the peptide. Naloxone was more potent in antagonizing morphine- than d-propoxyphene-induced antinociception in the mouse hot-plate test. In morphine-tolerant mice showing three-fold lower morphine sensitivity the antinociceptive efficacy of d-propoxyphene was unchanged. The results indicate differences in receptor-effector mechanisms between d-propoxyphene and morphine. PMID- 6258943 TI - alpha-Methylepinephrine, a methyldopa metabolite that binds to alpha-receptors in rat brain. AB - The presence of phenylethanolamine-N-methyl transferase in those brain-stem nuclei where methyldopa is thought to act suggested to us that methylepinephrine could be an active metabolite of methyldopa. We assessed the potential of methylepinephrine to be an active metabolite by determining its capacity to compete for ligands which bind to alpha-receptors in rat brain. Thus, the abilities of epinephrine, norepinephrine, methyldopa, (+/-)-methylnorepinephrine and (+/-)-methylepinephrine to compete for alpha 1-([3H]WB-4101) and alpha 2 ([3H]clonidine) binding sites in rat brain wee compared. Order of potency at each binding site was: [3H]WB-4101 -- (-)epinephrine = (-)-norepinephrine greater than (+/-)-methylnorepinephrine greater than (+/-)-methylepinephrine much greater than (-)-methyldopa; [3H]clonidine -- (-)-epinephrine greater than (+/-) methylnorepinephrine greater than (-)-norepinephrine greater than (+/-) methylepinephrine much greater than (-)-methyldopa. Since it can compete with a specific ligand for alpha 2-receptors, methylepinephrine could be a centrally active metabolite of methyldopa. PMID- 6258944 TI - Relationships between structure and alpha-adrenergic receptor affinity of clonidine and some related cyclic amidines. AB - The inhibition of specific [3H]clonidine binding to alpha-adrenergic receptors in rat brain has been studied for 43 compounds structurally related to clonidine. Oxymetazoline was found to be the most potent compound in displacing [3H]clonidine from its binding sites. 2-Methylimidazoline, 1,2,3,5 tetrahydroimidazo[2,1-b]quinazoline and heterocyclic N-methyl-substituted compounds showed no affinity at all for [3H]clonidine receptor sites. There was a good correlation between hypotensive activity and alpha 2-adrenergic receptor affinity to some 2-(phenylamino)imidazolidines. Parallelisms between Ki's and pharmacological activities were also observed for other compounds. Apparent structural requirements for alpha 2-receptor affinity were the presence of an aromatic moiety and a N-hydrogen in the heterocyclic ring. Ortho substitution in the phenyl ring was necessary for high affinity. Compounds with an oxazolidine ring had approximately similar affinities for the [3H]clonidine binding sites compared with the corresponding imidazolines (except for the 2,6-dichlorophenyl substituted compound) whereas the pyrrolidine derivatives showed a 10-fold weaker affinity. [3H]Clonidine sites showed a homogeneous character. KD values from saturation and displacement experiments were in good agreement with one another (2.6 and 2.7 nM, respectively) and with values in the literature. PMID- 6258946 TI - An attempt for eradication of Sendai virus from a mouse breeding colony. AB - Eradication of Sendai virus from an infected mouse breeding colony was successfully made by sacrificing all offspring younger than 5 weeks of age at a time and then newborns as well as severely affected breeder mice for successive 2 weeks. By this method, number of breeders decreased of two third of those in the original colony but recovered again about 2 months later. PMID- 6258945 TI - Vascular smooth muscle contraction initiated by postsynaptic alpha 2-adrenoceptor activation is induced by an influx of extracellular calcium. AB - Vasoconstriction in pithed, normotensive rats elicited via stimulation of postsynaptic alpha 2-adrenoceptors by B-HT 920 was antagonized by EDTA and the calcium antagonists nifedipine, D 600 and verapamil, whereas pressor responses to the alpha 1-agonist methoxamine were unaffected. This indicates that vasoconstriction in vivo initiated via postsynaptic alpha 2-adrenoceptors requires an influx of extracellular calcium. Thus, the antihypertensive effect of calcium antagonists may be based upon a diminution of vascular tone maintained by postsynaptic alpha 2-adrenoceptors. PMID- 6258947 TI - Purification and characterization of human lysosomes from EB-virus transformed lymphoblasts. PMID- 6258948 TI - Characterization of the hematopoietic target cells of AEV, MC29 and AMV avian leukemia viruses. PMID- 6258949 TI - Absence of a correlation between cyclic nucleotide fluctuations and cell cycle progression. PMID- 6258950 TI - Replacement of serum with a defined medium increases beta-adrenergic receptor number in cultured glioma cells. PMID- 6258952 TI - Analysis of mitochondrial DNA species in interspecific hybrid somatic cells using restriction endonucleases. Identification of recombinant mtDNA molecules. PMID- 6258951 TI - Rapid effects of nerve growth factor on the Na+, K+-pump in rat pheochromocytoma cells. PMID- 6258953 TI - Morphological changes in Ehrlich ascites tumor cells during the cell fusion reaction with HVJ (Sendai virus). II. Cluster formation of intramembrane particles in the early stage of cell fusion. PMID- 6258954 TI - Induction of cell DNA replication in G1-specific ts mutants by microinjection of SV40 DNA. PMID- 6258955 TI - Age-dependent modification of drug interference on the enzymatic activities of the rat brain. PMID- 6258956 TI - The ultrastructural immunocytochemical demonstration of erythropoietin receptors on developing erythrocytic cells of fetal mouse liver. AB - In spite of the severe restrictions imposed by the lack of high purity erythropoietin (Ep) and Ep specific antiserum wer have attempted to demonstrate presumptive Ep binding sites on the surface of developmental forms of erythrocytic cells of the mouse fetal liver using ultrastructural immunocytochemical methodology. Cells were exposed to exogenous Ep of differing potencies and concentrations and subsequently incubated in an Ep antiserum. The Ep-Ep-antiserum complex was then visualized with a gold-labeled IgG reagent. Limited surface labeling was noted on the developing erythrocytic cells and the evaluation of the mean surface labeling densities of the erythrocytic cell series indicated that the extent of labeling was related to the stage of maturation. Early polychromatophilic erythroblasts proved to be the most heavily labeled of the erythrocytic cells followed by the basophilic erythroblast, proerythroblast and late polychromatophilic erythroblasts respectively; normoblasts, reticulocytes and erythrocytes exhibited, at most, only minimal labeling. In addition, we have been able to demonstrate several primitive cells in the fetal liver which exhibited extensive surface labeling when compared with the developing erythrocytic cells. These cells may represent the erythroid precursors of the fetal liver. PMID- 6258957 TI - Adrenergic receptors and sympathetic agents in isolated human pulmonary arteries. AB - We tested the in vitro contractility of 88 segmental pulmonary arteries from 46 patients undergoing thoracic surgery. The vascular strips, taken from macroscopically healthy lung tissue, were devoid of spontaneous adrenergic tone. Cumulative dose-response curves with epinephrine and norepinephrine showed graded contraction. There was no significant difference between the two substances concerning mean maximal tension, threshold doses, ED50 or concentrations causing maximal contraction. Alpha-receptor blocking agents, phenoxybenzamine and indoramine, showed an inhibition of the contraction induced with both epinephrine and norepinephrine. Epinephrine in higher doses caused a dual response: contraction followed by relaxation. The latter was blocked by propranolol. Both isoproterenol and theophylline relaxed contracted vessels to some extent. Relaxation induced by isoproterenol could be blocked by propranolol. "Selective" beta2-stimulants such as terbutaline or salbutamol induced no relaxation. The results suggest the presence of alpha-receptors mediating constriction and possibly beta1-receptors mediating relaxation in human segmental arteries. PMID- 6258958 TI - Urinary cyclic adenosine 3',5'-monophosphate (cAMP) and cyclic guanosine 3',5' monophosphate (cGMP) in asthmatic and normal children. AB - Urinary excretion of cAMP and cGMP was studied in nine normal and 15 asthmatic children. Bronchial lability was studied with a treadmill running test and atopy with serum IgE and skin prick tests. A circadian rhythm was found in both groups for cAMP and cGMP excretion. Cyclic GMP levels were higher in the asthma group, the difference reaching statistical significance around the time of the exercise challenge test. The fall in PEF induced by exercise showed a significant negative correlation with urinary cAMP responsiveness to isoproterenol inhalation. Exercise-induced bronchial lability correlated with 24-h cGMP excretion. High cGMP and low cAMP levels at night could be connected with nighttime exacerbations of symptoms. It is suggested that cGMP might have a more important role in asthma, than previously assumed. PMID- 6258959 TI - Plasma cyclic AMP levels in response to exercise and terbutaline sulphate aerosol in normal and asthmatic subjects. AB - A study was performed to investigate changes in plasma cyclic adenosine monophosphate (cyclic AMP), peak expiratory flow and arterial blood gas tensions in response to running exercise and terbutaline sulphate aerosol in asthmatic patients regularly receiving sympathomimetic bronchodilator aerosols. Seven normal subjects were controls. Placebo aerosol was administered 20 min before the first exercise study and 1.0-1.25 mg terbutaline sulphate substituted 20 min after the first test and again 20 min before the second test. Blood gas tensions, expiratory flow and cyclic AMP were measured at rest, during and after exercise. Exercise induced a significant increase in cyclic AMP in both asthmatic and normal subjects. The change in plasma levels was not significantly different between groups. Cyclic AMP values were higher at rest and during exercise with terbutaline sulphate compared with placebo for both groups. Terbutaline sulphate blocked the marked fall in peak expiratory flow and arterial oxygen tension observed in the asthmatic subjects following the first test. Values for cyclic AMP following exercise were not significantly different between asthmatic and normal subjects. In contrast to other reports our asthmatics have a marked increase in cyclic AMP in response to exercise and to a beta-sympathomimetic aerosol. PMID- 6258960 TI - Effects of noradrenaline depletion on adrenergic and muscarinic cholinergic receptors in the cerebral cortex, hippocampus, and cerebellum. PMID- 6258962 TI - Regional changes in [3H]diazepam binding in the brains of mice after removal of the olfactory bulbs. PMID- 6258961 TI - Ectopic adrenergic sensitivity in damaged peripheral nerve axons in the rat. PMID- 6258963 TI - Hymenolepis diminuta: partial characterization of membrane-bound nucleotidase activities (ATPase and 5'-nucleotidase) in the isolated brush border membrane. PMID- 6258964 TI - Effects of scavengers of superoxide radicals, hydrogen peroxide, singlet oxygen and hydroxyl radicals on malondialdehyde generation from arachidonic acid by bovine seminal vesicle microsomes. AB - Superoxide dismutase, catalase and sodium formate did not inhibit the formation of malondialdehyde (MDA) from arachidonic acid, suggesting that O2-., H2O2 and OH. are not involved in the enzymatical oxidation of arachidonic acid. Sodium azide was found to be an inhibitor of MDA production. PMID- 6258965 TI - Reduction of ferricytochrome c by human red cells. AB - Human red cells reduced extracellular ferricytochrome c to ferrocytochrome c under various conditions, suggesting that ferricytochrome c reducing systems are present at the outer surface of the red cell membrane. PMID- 6258966 TI - The effect of physostigmine on (Na+ + K+)-ATPase activity in different rat brain regions. AB - The activity of (Na+ + K+)-ATPase and acetylcholine esterase were followed in rat brain cerebral cortex, caudate, thalamus, hippocampus and medulla after i.v. administration of physostigmine. Both enzymes were found to be inhibited in a dose-dependent manner. The most pronounced inhibition of (Na+ + K+)-ATPase was found in caudate, where the highest activity of acetylcholine esterase is found. PMID- 6258967 TI - Interaction between fluorescent-labeled ACTH1-24, isolated fat cells, and serum albumin. AB - Part of all of the difference in the ability of ACTH1-24, and a fluorescent labeled ACTH1-24 to activate lipolysis in fat cells can be accounted for by label related binding to albumin present in the assay medium. PMID- 6258968 TI - Drug action on adenylate kinase activity in cerebrospinal fluid of arteriosclerotic patients. AB - A manifest presence of adenylate kinase activity in cerebrospinal fluid was found in patients with cerebral arteriosclerosis. This activity was significantly higher during treatment with co-dergocrine (Hydergin) compared with the two periods before and after treatment. PMID- 6258969 TI - A postsynaptic alpha 2-receptor: the alpha-adrenergic receptor of hamster white fat cells. AB - The effects of selected alpha-agonists and alpha-antagonists on theophylline induces lipolysis were investigate in isolated hamster white fat cells, alpha 2 Agonists (tramazoline, clonidine) inhibited theophylline-induced lipolysis while in alpha 1-agonist (methoxamine) was without any effect. The inhibitory effect of alpha 2-agonists was suppressed by yohimbine (alpha 2-antagonist), whereas alpha 1-antagonists were inefficient. This result implies that the alpha-adrenergic receptor of hamster fat cells is of the alpha 2-type, although postsynaptically. PMID- 6258970 TI - Effect of prolactin on human red cell sodium transport. AB - Incubation of red cells with higher concentrations of prolactin in vitro enhanced the cellular sodium level and produced a significant reduction in erythrocyte membrane adenosine triphosphatase activity. This effect was dose and time dependent. It is the result of an inhibition of the active sodium pump similar to that produced by ouabain, suggesting altered red cell function and electrolyte balance in hyperprolactinemic states. PMID- 6258972 TI - [Intracellular cyclic AMP in vesicular stomatitis or Sendai virus infected cells (author's transl)]. AB - In KB cells, MRC5 and adult skin fibroblasts infected by low doses of Sendai virus, intracellular cyclic AMP levels rose and fell in the first hours following infection, then remained lower than basal level during at least 2 days in KB cells and adult skin fibroblasts. When compared to other viruses or cAMP inducers previously described, this effect appeared specific of Sendai virus. Mechanisms and roles of cAMP variations are discussed. VSV-infected KB cells showed slightly decreased cAMP levels during the first hours following infection. PMID- 6258971 TI - Effect of prostaglandins and dibutyryl cyclic AMP on the morphology of cells in primary astroglial cultures and on metabolic enzymes of GABA and glutamate metabolism. AB - Prostaglandins (PGE1) and dibutyryl cyclic AMP (dBc AMP) induce similar morphological changes in astrocytes obtained in primary cultures. PGE1 and dBc AMP increased 2 enzymes of GABA and glutamate metabolism, GABA-T and AAT, but did not modify GDH and GLN-S. Prostaglandins probably affect the cAMP content of glial cells and act in the same way as dBc AMP on glial cell differentiation. PMID- 6258973 TI - Cholecystokinin-induced hypothermia in the rat. AB - Cholecystokinin-octapeptide (CCK-8) was shown to cause hypothermia after intracerebroventricular administration in the rat, and the hypothermic effect of CCK-8 was antagonized by simultaneous injection of TRH. PMID- 6258974 TI - [Substances with antiviral. XVI. Thiosemicarbazones containing benzofuran and 1H indene moieties]. AB - A few hydrazones with benzofuran and 1H-indene moieties were synthesized and screened in vitro against vaccinia virus strain IHD, parainfluenza type 3 virus strain HA-1/CR-8, and the MP mutant of herpes simplex virus type 1 [HSV-1 (MP)]. Only the thiosemicarbazones were active. The thiosemicarbazone of 3-chloro-2 formyl-1H-indene inhibited vaccinia virus to a greater extent than methisazone, used as reference standard. Furthermore, this compound was active also against parainfluenza and herpes viruses. PMID- 6258975 TI - A probe for the organization of the beta-adrenergic receptor-regulated adenylate cyclase system in turkey erythrocyte membranes by the use of a complementation assay. PMID- 6258977 TI - Hydrodynamic properties of a [3H]etorphine macromolecular complex from the rat brain. PMID- 6258978 TI - The isolation and characterisation of a dimeric cyclic AMP-dependent protein kinase and of the corresponding R-subunit. PMID- 6258976 TI - Regulation of ovarian gonadotropin receptors and LH bioactivity during the estrous cycle. PMID- 6258979 TI - Autocatalytic phosphorylation of calsequestrin. PMID- 6258980 TI - Microsomal methoxymelanin formation from 6-hydroxymelatonin. PMID- 6258981 TI - Transverse localization of glycosyl transferases in rough and smooth microsomes. PMID- 6258983 TI - Spin trapping of free radical products of CC14 activation using pulse radiolysis and high energy radiation procedures. PMID- 6258982 TI - Two glycosylation sites on the N-terminal segment of porcine pars distalis pro opiomelanocortin. PMID- 6258984 TI - Localization of the 3'-terminal end of the EcoRI B fragment-specific early mRNA of adenovirus type 2. PMID- 6258985 TI - Membrane crystals of a subunit complex of mitochondrial cytochrome reductase containing the cytochromes b and c1. PMID- 6258986 TI - Reversibility of the inhibition of cytochrome c oxidase by reticulocyte lipoxygenase. PMID- 6258987 TI - A receptor for single segments of secretory proteins in rough endoplasmic reticulum membranes. PMID- 6258989 TI - Behaviour of normal and neoplastic rat cells on grooved substrates. AB - The distribution and shape of rat cells cultivated on plastic surfaces containing cylindrical areas of various radii and grooves of various depths were studied. Normal embryo cells and two lines of neoplastic cells (LW13K2 and RsK4) were used. The nuclear shape, orientation of the nuclei and migration of cells from the bottom of the grooves were assessed by quantitative methods. All characteristics of the behaviour of both neoplastic cell lines on the grooved substrates were found to be different from those of normal cells: a) the nuclei of neoplastic cells, in contrast to those of the normal ones, did not undergo additional elongation on the cylindrical areas of the substrate; b) the orientation of neoplastic cells with regard to the axis of the cylindrical substrate was decreased or absent; c) the migration of neoplastic cells from certain types of the grooves was decreased. It is suggested that the different reaction to the geometry of the substrate may be a characteristic feature of transformed cells. Possible mechanisms of these alterations are discussed. PMID- 6258988 TI - Steroid production and responsiveness to gonadotropin and prostaglandins of human ovarian follicles at term pregnancy. PMID- 6258990 TI - [The dynamics of glycerol and cAMP release from perfused isolated rat fat cells with epinephrine stimulation (author's transl)]. PMID- 6258991 TI - [A radioreceptor assay for catecholamines. III. A study on the binding sites of catecholamines to alpha-adrenergic receptors (author's transl)]. AB - We established a radioreceptor assay for catecholamines (CA), utilizing the microsomal fraction of bovine myocardium as CA receptors and 3H-norepinephrine (3H-NA) as a ligand. Since 3H-NA binding to the prepared CA binding protein was inhibited by alpha-adrenergic blocking agents, the CA receptors used were assumed to be alpha-adrenergic receptors. In this paper, we studied binding sites of CA to alpha-adrenergic receptors by a displacement study using such compounds as CA, CA metabolites, substances of dihydroxytetrahydronaphthalene derivatives, and other compounds. Various compounds with catechol nucleus had an affinity to the CA binding protein. The displacement study with compounds which were capable of binding to alpha-adrenoceptors had 2 neighbouring phenol groups in the benzenee ring at either position 2 and 3, or at position 3 and 4. On the other hand, either phenylalanine or tyrosine, which has only one phenol group in the benzen ring, did not bind the receptors. It is conceivable, therefore, that the binding sites of CA to alpha-adrenergic receptors is position 2 to 4 of the catechol nucleus, where 2 neighbouring phenol groups exist. PMID- 6258992 TI - The influence of age and pregnancy on immune responses of baboons to mitogens and the baboon endogenous virus. PMID- 6258993 TI - Intracranial growth of pulmonary small cell carcinoma cells in nude athymic mice. AB - Pulmonary small cell carcinoma of the lung cells were inoculated intracranially and subdermally in nude athymic mice (Balb/c strain). There was a 100% intracranial tumor incidence in response to 1/10th the cell dose required to produce subdermal tumors in immunosuppressed nude mice. Tumors did not grow in the brains of Balb/c normal (haired) mice. PMID- 6258994 TI - Binding proteins for cyclic AMP in mammalian tissues. PMID- 6258995 TI - Biochemical abnormalities in the Chinese hamster (Cricetulus griseus) with spontaneous diabetes. PMID- 6258996 TI - Enzyme activities in liver and brain fractions from alcoholic and control rats. PMID- 6258997 TI - The specificity of the Bacillus amyloliquefaciens intracellular serine protease: a comparison with the specificity of secretory subtilisins. PMID- 6258998 TI - Inhibitory effect of deuterium oxide on glucose oxidation by pancreatic islets. AB - The inhibition of insulin release by deuterium oxide has been interpreted by its stabilizing action on the microtubular system of the beta-cell. Because only indirect information exists about beta-cell metabolism in the presence of D2O, the effect of D2O (99.7%) on glucose oxidation by pancreatic islets was studied. Heavy water reduced 14CO2 formation from [U-14C]glucose (16.7 mM) by ob/ob mouse and rat islets by 50 and 30%, resp. Omission of calcium from H2O-containing media resulted in a 40% diminished glucose oxidation by ob/ob mouse islets. In the absence of calcium, D2O led to a further decrease in 14CO2 production (60%). Erythrocytes oxidized similar amounts of glucose in the absence and presence of D2O. Effects of D2O on glucose transport and mitochondrial respiration are discussed as possible causes of the decreased 14CO2 formation in islet tissue. It is concluded that the inhibition of insulin release by D2O need not necessarily be ascribed to its stabilizing effect on microtubules, but may also be due--at least in part--to the reduction of islet glucose oxidation. PMID- 6258999 TI - Non-linear coupling between receptor occupancy and biologic effect as a requirement for a higher drug efficacy. AB - Pharmacological drugs activate cellular functions by binding to specific receptors. Experimental observations have shown that, in many systems, the drug effect is half-maximally elicited at drug concentrations far lower than those required for saturating half the receptors. In the case of the beta-adrenergic system, such a discrepancy can be correlated with the efficacy of agonists in activating the adenylate cyclase. It is shown in this paper that, within the framework of discrepancy between binding and activation is a direct consequence of the structure of the system and is, in fact, an index of the drug efficacy. PMID- 6259000 TI - Modulation of steroidogenic activities in testis Leydig cells. AB - Recent developments in the regulation of testicular Leydig-cell function support the following conclusions. (1) Enzymic activities involved in steroid production in the testis are mainly localized in Leydig cells. The aromatase enzyme complex for oestrogen production appears to be localized in Leydig cells as well as in Sertoli cells. (2) LH- (or hCG-) induced alterations of Leydig cells depend on dose and duration of exposure of the cell to the hormone. Locally produced oestradiol is probably involved in the inhibition of steroidogenesis. (3) The stimulatory action of LH on Leydig cells involves different proteins in concert with the activation of the cleavage activity of mitochondrial cholesterol side chain. However, most of the functional properties of these proteins are yet unknown. (4) Different populations of Leydig cells are present in the testis. These different cell populations can be characterized by quantitatively and qualitatively different responses to hormones. PMID- 6259001 TI - Inhibition by Ca2+ of the incorporation of myo-inositol into phosphatidylinositol. AB - The incorporation of myo-[2-3H]inositol into phosphatidylinositol of the aorta and the vas deferens was measured and the effects of Ca2+ and other divalent cations were determined. When incubated in normal Krebs-Ringer buffer, only negligible radioactivity was incorporated into aorta slices. Mn2+ increased the incorporation greatly. The enhanced incorporation was attributable to an increase in CDP-diglyceride:inositol transferase activity, rather than the myo-inositol exchange reaction. Transferase activity was increased 20-fold by 1 mM Mn2+, in the presence of 20 mM Mg2+. The Mn2+-stimulated activity was strongly inhibited by Ca2+. In the absence of Mn2+, but presence of 20 mM Mg2+, transferase activity was inhibited 80% by 0.01 mM Ca2+. Removal of endogenous Ca2+ from the tissue by ionophore A23187 and EGTA increased the incorporation of myo-[2-3H]inositol into phosphatidylinositol. These findings indicate that Ca2+ inhibited the synthesis of phosphatidylinositol. The proposed action of cholinergic and alpha-adrenergic agonists in enhancing the degradation and turnover of phosphatidyl-inositol and in provoking the influx of Ca2+ should be unfavorable to the recovery of cellular phosphatidylinositol content. PMID- 6259002 TI - Additive inhibitory effects of treatment with an LHRH agonist and an antiandrogen on androgen-dependent tissues in the rat. AB - Combined treatment of adult male rats with the LHRH agonist, [D-Ser(TBU)6, des Gly-NH2(10)]LHRH ethylamide, and a non-steroid antiandrogen, RU 23908, led to a rapid and marked atrophy of the ventral prostate and seminal vesicles. Treatment with the LHRH agonist decreased androgen secretion and thus facilitated the action of the antiandrogen in androgen-dependent tissues. Such a combined treatment could be useful in the treatment of androgen-dependent pathologies in man, particularly in prostatic adenocarcinoma and possibly benign prostatic hyperplasia. PMID- 6259004 TI - Preponderance of beta-adrenergic binding sites in pancreatic islet cells of the rat. AB - Although the alpha- and beta-adrenergic receptors have opposing effects on insulin secretion, the inhibitory influence of alpha-receptors appears to predominate. To determine if this was due to differences in number and affinity of receptors, isolated rat pancreatic islet cells were incubated with [3H] dihydroalprenolol and [3H]-dihydroergocryptine as ligands for beta- and alpha adrenergic binding sites. It was found that the number of beta-adrenergic binding sites was 143 fmol/mg islet protein with a Kd = 0.57 nM. The number of alpha adrenergic binding sites was 53 fmol/mg protein with a Kd = 0.26 nM. Thus, there are 2.7 times as many beta-adrenergic binding sites as alpha-binding sites, and neither binding site number nor affinity is responsible for the predominant influence of the alpha-adrenergic receptors. PMID- 6259003 TI - Guanine nucleotides modulate TRH-receptor binding in sheep anterior pituitary. AB - Binding of thyrotropin-releasing hormone (TRH, thyroliberin) to receptors in chilled membrane resuspensions from sheep anterior pituitary glands is reduced in affinity almost 2-fold by micromolar concentrations of guanosine 5'-triphosphate (GTP) and the hydrolysis-resistant analog guanyl-5'-yl imidodiphosphate (GppNHp) added to tissue during a 10-min preincubation at 37 degree C. Guanosine 5' diphosphate (GDP) produced a similar effect at 1 mM, while GMP, ATP, ADP and AMP appeared relatively inactive. The number of TRH-binding sites was not affected by the nucleotide treatments. These results are consistent with reports of guanine nucleotide effects on other receptor types and with evidence suggesting an adenylate cyclase mechanism for some of TRH's effects in the anterior pituitary. PMID- 6259005 TI - Prolongation of islet xenograft survival (rat to mouse). PMID- 6259006 TI - Insulin release in vitro from islet tissues and adenomas of rats treated with nicotinamide and streptozotocin. The effects of glucose. AB - Young male Holtzman rats injected with nicotinamide and streptozotocin develop grossly visible tumors of pancreatic islet tissue. Using an i.v. glucose tolerance test, some tumor-bearing animals exhibited a vigorous (or fast) response to glucose loading (Diabetic Index = 0.47), whereas others showed a subdiabetic (or slow) response (Diabetic Index = 2.34). In vitro perifusion studies demonstrate that tumor pieces from both groups of rats released immunoreactive insulin (IRI) in response to glucose; tumors from fast responding rats showed a rapid monophasic release of IRI (i.e., rapid transient release with little secondary phase), while tumors from slow responders released IRI in a biphasic pattern resembling that of normal islets. A population of large islet masses (or microscopic tumors), isolated from drug-treated rats by collagenase digestion of the pancreas of tumor-containing rats, exhibited glucose-stimulated IRI release that resembled the pattern of the tumor from the same animal. Isolated islets of Langerhans of ordinary size from the pancreas of tumor-bearing rats, on the other hand, usually exhibited a normal (biphasic) IRI release pattern in response to glucose. Analysis by gel filtration suggests that the predominant form of IRI released from perifused tumor preparations, under either basal or glucose-stimulated conditions, eluted at a rate corresponding to rat insulin. PMID- 6259008 TI - Effects of dietary fibre supplementation in stable and labile insulin-dependent diabetics. PMID- 6259007 TI - Long-term prognosis after infantile spasms: a statistical study of prognostic factors in 200 cases. AB - A follow-up study was made on 200 children (115 boys, 85 girls) who had had infantile spasms, in order to compare their present condition over the age of six years with various prognostic factors. 48 of the children (30 males and 18 females) had died, and all the rest were aged six years or older at the time of final follow-up. 139 of the children had received ACTH therapy: at final follow up, spasms had ceased in 43.5 per cent, and about the same proportion showed normal physical development; 23 per cent had normal mental development and 15.4 per cent were attending ordinary schools. Complete recovery (normal mental and physical development and attending ordinary schools) was achieved in only 19 cases (9.5 per cent). Of the cryptogenic cases, 44.4 per cent had made a full recovery. The poor prognostic factors for continuing seizures were evolution into other types of fits, relapse of seizures after ACTH therapy, seizures concomitant with spasms, and convulsions before the onset of spasms. Poor prognostic factors for physical development were delayed development before the onset of spasms, neurological abnormalities, PEG abnormality, symptomatic aetiology, neonatal convulsions, low birthweight, perinatal asphyxia and being female. Poor prognostic factors for mental development were delayed development before the onset of spasms, neurological abnormalities, PEG abnormality, prenatal and perinatal aetiology, relapse after initial ACTH therapy, laughing attacks, and evolution into other types of fits. Only in the cryptogenic cases was there significant correlation between the delay in treatment and the long-term prognosis for mental development. Poor prognostic factors for educability were very similar to those for mental development. In spite of conflicting views as to the long-term effects of ACTH, prompt treatment seems to be mandatory, at least in cryptogenic cases of infantile spasms. PMID- 6259009 TI - Diets rich in natural fibre improve carbohydrate tolerance in maturity-onset, non insulin dependent diabetics. AB - The influence of low and high fibre diets upon carbohydrate tolerance was examined in five maturity-onset, non-insulin dependent diabetics. After 14 days on a diet rich in natural fibre (30 g/day), the subjects consumed a high fibre (13 g) test meal. They then ate a low fibre diet (10 g/day) followed by a low fibre (1 g) test meal. Mean basal plasma glucose concentrations were similar after both fibre diets; however, both mean basal plasma insulin and gastric inhibitory polypeptide (GIP) were significantly lower after the high fibre diet. After the high fibre test meal, significantly lower mean plasma glucose, insulin and GIP concentrations were measured. This study is the first study to demonstrate the ability of an institutionally supervised diet of natural foodstuffs rich in fibre to improve carbohydrate tolerance in maturity-onset, non insulin dependent diabetics. This findings is relevant to the dietary management of diabetics. PMID- 6259011 TI - [Features of gastroenteritis caused by rotavirus]. PMID- 6259010 TI - Therapy of malignant hamster insulinomas with monoamine precursors. PMID- 6259012 TI - Lack of relationship between prolactin binding and growth rate of carcinogen induced mammary tumors or circulating levels of mammotropic hormones in rats. PMID- 6259014 TI - Effect of dietary fiber on gastrointestinal motility and jejunal transit time in dogs. AB - Strain gauge recordings of the motility of the antrum, duodenum, and jejunum were made in 10 dogs receiving a daily meal of canned food. Addition of 30 g of either wheat bran, cellulose, or guar gum increased the duration of the postprandial pattern of motility by 41-54% in the duodenum. Only cellulose and gum caused increases in the duration of the postprandial pattern of motility in the jejunum. The normal postprandial pattern of duodenojejunal contractions consisted of bursts of 4-10 rhythmic contractions. When bran or cellulose were added, the bursts were prolonged (12-15 contractions per burst) with 4-15 min intervals between bursts. In contrast, when gum was added, contractions occurred continuously at a rate of 7-8/min, but their amplitude was one-half that seen with the other fibers. The increased number of low amplitude contractions when gum was added caused the postprandial motility index to double. There was no change in the motility index when cellulose was added. Guar gum also increased the frequency of antral contractions by 129%, while bran and cellulose had no effect. Jejunal transit time and flow of digesta were measured in four dogs 2 h after the meal. Addition of bran or gum increased the transit time by 28% and 51%, respectively, but cellulose caused a 900% increase in transit time associated with a 50% reduction in the flow of digesta. Addition of different fibers causes different alterations in postprandial motility. Jejunal transit of digesta appears unrelated to the pattern of contractions. PMID- 6259013 TI - Transport of fluorescent compounds into hepatocytes and the resultant zonal labeling of the hepatic acinus in the rat. PMID- 6259015 TI - Myoelectric activity in the small intestine in response to Clostridium perfringens A enterotoxin: correlation with histologic findings in an in vivo rabbit model. PMID- 6259016 TI - Chi mutation in a transposon and the orientation-dependence of Chi phenotype. AB - Chi, an element that stimulates recombination via the E. coli RecBC pathway, can arise by spontaneous mutation in the transposon Tn5. When in phage lambda in one orientation, the mutant transposon confers Chi+ phenotype (large plaque and a high rate of exchange near the transposon). In the other orientation, however, the transposon does not confer Chi+ phenotype. The mobility of the transposon allows us to show that the Chi+ orientation of the mutant Tn5 is the same at different locations in lambda. These include a site near gene J, one in gam at 69, one to the right of gam at 73 and several to the right of R between 95.7 and 99.5. To the right of R, the mutant transposon could be found in only one orientation, that which confers Chi+ phenotype. We speculate that the other orientation of Tn5 in that locale is lethal to lambda. The orientation-dependence of Chi+ phenotype also revealed that Tn5 flip-flops in lambda. PMID- 6259017 TI - [Medical aspects of using pesticides and mineral fertilizers in sugar beet cultivation]. PMID- 6259018 TI - [Standardization of the concentration of natural radionuclides in phosphorus fertilizers]. PMID- 6259019 TI - [Degree of interrelationships of phagocytosis, the enzymatic and sympathetic adrenal systems as a criterion of the body functional state]. PMID- 6259020 TI - [Health and hygiene evaluation of granodiorite, a filtering material for treating drinking water]. PMID- 6259021 TI - Case control study of high-risk factors in ovarian carcinomas. PMID- 6259023 TI - A clinical study of congenital anomalies of the hand. AB - The author has studied the clinical features of split hand, syndactyly, radial and ulnar ray deficiency, and brachydactyly. Many clinical findings make clear that typical split and is not a result of failure of formation but a result of union of digital rays. If we would try to classify congenital anomalies of the hand on the basis of embryological failure, syndactyly and split hand, and webbed and web free brachydactyly are never classified into other categories, just as constriction band syndrome is not divided by the presence of union of the digital rays. PMID- 6259022 TI - Fine needle aspiration cytology of supraclavicular lymph nodes in gynecologic malignancies. PMID- 6259024 TI - [The converting enzyme in the renin-angiotensin system]. PMID- 6259026 TI - Changes in the cell surface architecture in normal and polyoma virus transformed hamster cells after infection with influenza virus. AB - Test of Con A induced cell agglutination, method of binding cells to Con A coated nylon fibres and modified procedure of cell-to-cell binding were used in the investigation of architectural surface changes in normal and polyoma virus transformed hamster cells infected with influenza virus. In both cell types influenza virus infection caused 1) increase in fixation resistant Con A agglutination, 2) decrease in the level of surface membrane fluidity and cell plasticity. It has postulated that influenza virus infection results in stabilization of the cell surface architecture. These changes are amplified by polyoma virus transformation. Con A acts in this system, as an indicator rather than as a modifier of architectural changes. PMID- 6259025 TI - Morphochemical investigations of the liver and biochemical studies of the blood of guinea pigs in anaphylactic shock. AB - The experimental investigations have been carried out on 116 guinea pigs divided in two groups: the experimental and control group. The animals of the experimental group were sensitized with a 25% egg white suspension in 0.86% conc. of NaCl applied subcutaneously. After 21 days the same animals were exposed to the action of the same antigen in aerosol according to the method of Gerszanowicz, [16]. It has been shown, that in anaphylactic shock (acute and chronic) the damage of the lysosomal membranes in hepatocytes appeared which may be the cause of liberation among others also of acid phosphatase from the liver into the blood. Histochemically it was found a low phosphorylase and glucose-6 phosphatase activity, which was the basis of the assumption, that in anaphylactic shock we have to do with an enzymatic block--phosphorylase kinase--phosphorylase and inhibition of the enzymatic activity of glucose-6-phosphatase in the liver of guinea pigs. The comparison of the histochemical and biochemical results concerned with the amount of lipids, glycogen and nucleic acids in the liver revealed that the increasing amount of lipids is paralleled by decrease of glycogen. Among nucleic acids a growing level of ribonucleic acid was found while the level of the desoxyribonucleic acid remained stable. PMID- 6259027 TI - Enzymes of neutrophils in women with malignant tumors of reproductive organs. AB - Enzymatic equipment in peripheral blood neutrophils has been determined in 10 women with cervical carcinoma, 5 with carcinoma of the uterus body and 30 women with myomas of the uterus. Using cytochemical techniques the authors observed the intracellular deficiency of N-acetyl-beta-glucosaminidase accompanied by diminished absolute count of the enzyme-positive cells as well as the beta glucuronidase- and the myeloperoxidase-positive neutrophils. Lowered activity of the myeloperoxidase was another pattern of cells in question. The acid phosphatase activity of neutrophils in the patients was significantly elevated. It has been suggested that observed intracellular deficiencies of selected enzymes within the neutrophils are of importance with regard to lowered antitumor activity of that cells operating mainly through the myeloperoxidase-H2O2-halide system. PMID- 6259028 TI - Activity of some respiratory and lysosomal enzymes of lymphocytes in golden hamster with induced melanoma. AB - A considerable increase in activity of the following enzymes: succinate dehydrogenase (SDH), lactate dehydrogenase (LDH), beta-hydrogenase (beta-HBDH), cytochrome oxidase (CO), and acid phosphatase (AP) was found in lymph nodes lymphocytes after 1 week of malignant melanoma passage in golden hamster (Mesocricetus auratus Waterhouse). The peripheral blood lymphocytes displayed, too, an increase in activity of all the enzymes mentioned except beta-HBDH and SDH. After 3 weeks of the melanoma growth, the animals affected showed a considerable decrease in activity of all the enzymes studied both in the lymph nodes and in the peripheral blood. The increase in enzymatic activity during the initial phase of tumour growth may be a manifestation of biological activation of the cellular defence of lymphocytes. On the other hand, the decrease in the activity seen at the advanced phase of the disease speaks for an impaired immune response. PMID- 6259029 TI - [Tolerance to and dependence on opioids in isolated longitudinal muscle of guinea pig ileum. Validity of the muscle preparation as a receptor model for opioids (author's transl)]. AB - Contractions evoked by electrical stimulation of isolated longitudinal muscle preparations of guinea pig ileum were inhibited by the addition of opioids in the order of morphine = methionine enkephalin greater than pentazocine pethidine. Incubation of the preparation in the medium containing opioids at 4 degrees C for 22 hr resulted in a tolerance to the inhibitory effect in morphine and pethidine but in the case of pentazocine and met-enkephalin tolerance did not develop under the conditions employed. The same treatment with morphine, pethidine and pentazocine resulted in the development of dependence as demonstrated by naloxone provoked contracture or increase in the height of contraction. Opiate and enkephalin receptors are known to be unevenly distributed in the ileum and a significant difference was also observed in the distribution patterns of both receptors. Distribution of the receptors did not parallel the effect of opioids, thereby indicating a multiplicity in receptors. However, under the conditions employed in the present experiments, our results reflect the in vivo effects of opioids, such as analgesic effect or tolerance and dependence liability, and the validity of this preparation for the evaluation of opioids was confirmed. PMID- 6259030 TI - [Functional development of the synaptic transmission in the rat CNS and its interaction with drugs (author's transl)]. AB - The ontogenesis of the synaptic function was investigated in the central noradrenaline (NA), dopamine (DA), serotonin (5-HT), acetylcholine (ACh) and GABA nervous systems of developing rats. Monoamines histochemically first appeared on days 12 to 14 in the fetal brain and may exert a trophic action on target neurons as a "differentiation signal". The presynaptic functions such as the high affinity uptake and depolarization-induced, Ca2+-dependent release of L-[3H]DA, and [2H]DA, and [3H]DA, and [3H]5-HT were observed in synaptosomes and slices from the fetus (18 days of gestation) and brain of newborn rats. Monoamine stimulated activity of adenylate cyclase and specific binding of ligands in NA(alpha 1, alpha 2, beta 1, beta 2), DA, 5-HT, ACh (muscarinic and nicotinic) and GABA receptors indicated dynamic changes through postnatal development. Behavioral findings suggest when neurotransmitter receptors become sensitive and reach functional maturity (NA and DA, already at birth; 5-HT and muscarinic ACh, 15 to 20 days; GABA, 12 to 13 days (mouse)). In addition, differences in behavioral responsiveness to drugs were observed in rats at various developing stages, probably due to the interaction between plural neuronal systems. Finally, the brain undergoing rapid differentiation seems to be most sensitive to hormones and centrally acting drugs. Thus, permanent alteration in central functions may occur when some classes of drugs, dose-dependently, are administrated to animals at the perinatal stage. PMID- 6259032 TI - More on isocyanate sensitization. PMID- 6259031 TI - Catabolite repression during single and multiple induction in Escherichia coli. AB - Intracellular concentration of cAMP regulates the synthesis of enzymes sensitive to catabolite repression. The relationship between the single and multiple induction of beta-galactosidase (EC 3.2.1.23), L-tryptophanase (EC 4.1.99.1), D serine deaminase (EC 4.2.1.14), L-asparaginase (EC 3.5.1.1) and L-malate dehydrogenase (EC 1.1.1.37) was studied and the effect of cAMP level on the induction in Escherichia coli Crookes (ATCC 8739) was investigated. A varying degree of catabolite repression was observed during induction of individual enzymes induced separately on different energy sources. The synthesis of l tryptophanase was most sensitive, whereas l-asparaginase was not influenced at all. Exogenous cAMP was found to overcome partially the catabolite repression of beta-galactosidase and D-serine deaminase, both during single induction. The synthesis of l-malate dehydrogenase was negatively influenced by the multiple induction even in the presence of cAMP; on the other hand, the synthesis of l tryptophanase was stimulated, independently of the level of the exogenous cAMP. Similarly, the activity of L-asparaginase slightly but significantly increased during the multiple induction of all five enzymes; here too the activity increase did not depend on exogenous cAMP. PMID- 6259033 TI - The variability of dietary fibre in laboratory animal diets and its relevance to the control of experimental conditions. PMID- 6259034 TI - Angiographic demonstration of simultaneous appearance of cystadenoma and non functioning insuloma of the pancreas. PMID- 6259035 TI - [Chronic hypophosphatemic osteopathy (author's transl)]. AB - The process of chronic hypophosphatemic vitamin D-resistant rickets--observation of two cases. With the male patient--our first case--the disease was sporadic and had not been recognized for a long time. In his early adulthood it manifested itself as Umbauzonen (pseudofractures) in the larger context of active osteomalacia. It was possible to observe the pseudofractures before and while the patient was treated with drugs. High doses of vitamin D 3 and dosage of phosphate mitigated the complains although with respect to the radiological, scintigraphic, humoral and histological findings there was only slow improvement or no improvement at all.--The patient's daughter is affected by the disease as well. In her case the pathological signs of her bones became better when treated with vitamin D 3. PMID- 6259036 TI - Effects of antigastrin drugs on the interaction of 125I-human gastrin with rat gastric mucosa membranes. AB - A method for studying the interaction of 125I-human gastrin with a rat gastric mucosal membrane fraction is described, and the saturability, high affinity and reversibility of the preparations, as well as the correlation of pharmacological responses to antigastrin-drugs with the observed binding are discussed. Proglumide and other antigastrin drugs inhibit gastrin binding in a dose dependent way, and their activities in such a system are well correlated with the "in vivo" antisecretory activities of these drugs. PMID- 6259037 TI - Hepatic prolyl hydroxylase activity in human liver disease. AB - The activity of prolyl hydroxylase was measured in liver tissue obtained from a small series of patients with a variety of liver disease. Enzyme levels were marginally elevated in patients with fatty liver and viral hepatitis, conditions not normally associated with progressive fibrosis. In some patients with alcoholic hepatitis and in all patients with cirrhosis and chronic active hepatitis, there was a marked increase in enzyme activity. Patients with conditions characterised by high liver prolyl hydroxylase levels showed histological evidence of extensive hepatic fibrosis and also significant increases in the serum values of glutamate dehydrogenase and gamma-glutamyl transpeptidase. Prolyl hydroxylase activity was not detected in serum. PMID- 6259038 TI - Focal nodular hyperplasia of the liver and hepatic cell adenoma in women on oral contraceptives. AB - The article reports on the respective occurrence of focal nodular hyperplasia and hepatic cell adenoma in the liver of two women on oral contraceptives. The hepatic cell adenoma showed serious vascular lesions, including peliosis hepatis. Both tumors were removed surgically, and the patients are well. A possible relationship between oral contraception and benign hepatic tumor genesis is discussed under consideration of the pertinent literary data. PMID- 6259039 TI - [Human fetal-type thymidine kinase isozyme F: purification and biochemical characterization (author's transl)]. PMID- 6259040 TI - Effect of hydrocortisone on ACTH, growth hormone, insulin and glucose in the blood of bilaterally adrenalectomized patients. AB - This study is aimed at elucidating the mechanism of paradoxical rise in plasma ACTH levels in response to glucocorticoids, observed by several authors in bilaterally adrenalectomized patients with Cushing's disease. Six control subjects and fourteen patients bilaterally adrenalectomized for Cushing's disease were given a dose of 200 mg hydrocortisone sodium succinate by 3-5 mm i.v. injection. Plasma ACTH (in 6 patients), serum cortisol, growth hormone (GH) and insulin and blood glucose levels were estimated at 0, 30, 60, 90, and 120 minutes. The administration of hydrocortisone significantly suppressed plasma ACTH levels only at 60 min. In one case a slight rise in ACTH level during the test was observed. A significant fall in blood glucose levels was found only in the adrenalectomized patients. No significant changes in serum insulin and GH levels were noted. The possible mechanisms are discussed, especially the potential role of transient glucose deficiency in the pathophysiology of plasma ACTH increase in response to hydrocortisone in the bilaterally adrenalectomized patients. PMID- 6259041 TI - Ipodate and 8-anilino-1-naphthalene sulfonic acid block receptor binding of T3 in rat liver. AB - We have determined that 8-anilino-1-naphthalene sulfonic acid (ANS) and ipodate are effective inhibitor in vitro of 125I-T3 binding to rat hepatic nuclei receptors. Both of these agents are estimated to have a Kd for the T3 receptor of about 1--2 x 10(-4) M. Indirect preliminary studies suggest that ANS is a non competitive inhibitor and ipodate is a competitive inhibitor of T3 binding. Compounds such as tyropanoate and diatrizoate and iodide had no effect on T3 receptor binding. Further in vivo studies with ipodate suggested that T3 receptor binding inhibition also occurred when ipodate was given intravenously to rats. PMID- 6259042 TI - Effects of salbutamol and butoxamine on the human fat cell adenylate cyclase. AB - In order to characterize the beta-adrenoceptors coupled to the human fat cell adenylate cyclase more extensively the effects of the beta 2-selective agonist salbutamol on basal and isoproterenol-stimulated rates of cAMP-accumulation were studied. Although exhibiting only low intrinsic activity salbutamol displayed only slightly lower affinity towards the beta-adrenoceptors linked to the human fat cell adenylate cyclase than isoproterenol. In addition, the beta 2-selective antagonist butoxamine was slightly more potent in inhibiting the isoproterenol stimulated fat cell enzyme than the cardioselective beta-blocking agent practolol. These results further emphasize the difficulties in classifying the lipolytic response of adipose tissue to beta-adrenergic agonists and antagonists within a uniform beta-receptor theory. PMID- 6259043 TI - Thyroid hormone stimulation of lipolysis and cyclic adenosine 3', 5' monophosphate accumulation in human adipose tissue. AB - The role of thyroid hormones on lipolysis in human subcutaneous adipose tissue was investigated. Incubation of subcutaneous fat pads with thyroxine (0.1--10 000 nM) augmented the subsequent isoproterenol stimulation of lipolysis, measured by glycerol release. The basal lipolysis could not by stimulated by thyroxine. The theophylline- and dibutyryl-cyclic AMP stimulated lipolysis also could not be increased by thyroxine at these concentrations. In separate studies, the effect of thyroxine (0.01 pM--1 microM) and triiodothyronine (0.01 pM--1 microM) on cyclic AMP accumulation was examined. No effect of thyroid hormones on cyclic AMP accumulation was seen in non-isoproterenol stimulated tissue. Fat pads stimulated by isoproterenol and then treated with thyroid hormones showed marked increases in accumulation of cyclic AMP as compared to control tissue in the presence of isoproterenol alone. PMID- 6259044 TI - Simultaneous radioimmunoassay of androstenedione, dehydroepiandrosterone and 11 beta-hydroxyandrostenedione in plasma. AB - A simultaneous radioimmunoassay for delta 4-androstenedione (delta 4), dehydroepiandrosterone (DHA) and 11 beta-hydroxyandrostenedione (11 beta OH delta 4) in plasma is described. This involved preparing first an anti-11 beta hydroxyandrostenedione-3-0-carboxymethyl oxime/BSA antiserum which binds both delta 4 and 11 beta OH delta 4, and an anti-dehydrosterone-7-0-carboxymethyl oxime/BSA antiserum. A chromatographic step using celite minicolumns separates these three steroids. The method was applied to the measurement of the plasma basal values of these three androgens in control subjects. Mean concentrations (ng/ml) of delta 4, DHA and 11 beta OH delta 4 were respecstively 1.35, 6.63 and 3.13 in males; 1.35, 6.65 and 2.59 in premenopausal females; 0.46, 1.53 and 1.38 in post-menopausal females, and 0.39, 0.73 and 1.78 in children 1--6 years of age. Dynamic tests were also carried out: ACTH stimulation was found to increase delta 4, DHA and 11 beta OH delta 4. Dexamethasone had a reverse effect causing a 50% diminution in delta 4 levels, a marked decrease in DHA levels, and a 90% decrease in 11 beta OH delta 4 levels. Metyrapone test was found to produce a 223% increase in delta 4 levels, a 196% increase in DHA levels, and a decrease of more than 90% in the 11 beta OH delta 4 levels. Estroprogestative drug treatment was accompanied by a decrease of not only delta 4, but also of DHA and 11 beta OH delta 4. Preliminary clinical results concerning these steroids show a parallel increase or decrease of delta 4 and 11 beta OH delta 4 in adrenal pathology. In ovarian hyperandrogeny, delta 4 is increased and 11 beta OH delta 4 is unchanged. PMID- 6259046 TI - The evolution of an acute day treatment program. AB - The day treatment program of a community mental health center has evolved from a relatively unstructured drop-in-program set up ten years ago to a comprehensive four-part service. The acute day treatment program is able to provide transitional services to meet the needs of three local inpatient units and an alternative to inpatient care to clients with an adequate community support system. The unit has also developed an extended and less intensive program for clients who need services beyond the maximum 14 weeks of the basic program and a long-term aftercare medication and monitoring clinic. PMID- 6259045 TI - Perinatal activity of the hypothalamic-pituitary-gonadal axis in the lamb. II. In vitro testicular response to human chorionic gonadotropin and choleratoxin in the first 2 months of life. AB - Testicular response to human chorionic gonadotropin (hCG) was studied in male lambs. Adenosine 3':5'-cyclic monophosphate (cAMP), testosterone (T), delta 4 androstenedione and 17 alpha-hydroxyprogesterone content and cAMP and T production by dispersed interstitial cells were assessed in control and hCG pretreated animals. Plasma T levels increased after hCG at 1, 4 and 8 weeks. Increments in the testicular content of cAMP, delta 4-androstenedione, and T were greater at 8 weeks and that of 17 alpha-hydroxyprogesterone and 125I-hCG binding to dispersed interstitial cells were identical at all ages. cAMP and T production by dispersed interstitial cells from nonstimulated animals and the response to hCG and choleratoxin were similar in all lambs. In contrast, cAMP and T production were higher at 1 week only in animals pretreated with hCG in vivo. These data are compatible with hCG-induced desensitization at 4 and 8 weeks. PMID- 6259047 TI - Discharged patients who desire to return to the hospital. AB - Since the implementation of deinstitutionalization policies began in the early 1960s, large numbers of patients have been discharged from state mental hospitals to the community. Given the negative aspects of institutional life, it was assumed that patients would rather live in the community than remain confined in a state mental hospital. However, little is known about the actual preferences of discharged mental patients. In interviews with 176 patients an average of one year after their release from three state mental hospitals in Massachusetts, the author found that one-fourth indicated a desire to return to the hospital at some time since release. Significant factors associated with the patients' desire to return included self-image, relationships with others, and use of leisure time. The study results suggest that aftercare programs have not adequately met the needs of these patients. PMID- 6259048 TI - Autoimmune antireceptor diseases. PMID- 6259049 TI - The neuropathology of rheumatoid disease. AB - Patients with active rheumatoid disease may develop encephalopathy, myelopathy, peripheral neuropathy, and myopathy through a variety of tissue mechanisms. Brain involvement is usually characterized by the formation of rheumatoid nodules or by the development of vasculitis or its complications, and there is evidence to suggest that the trapping of immune complexes within the choroid plexus may be important in pathogenesis. Structural damage to the spinal cord and lower brain stem, on the other hand, most commonly results from narrowing of the bony canal, leading either to direct compression of neural tissue or to compromise of its vascular supply. The appearance of peripheral neuropathy generally signifies the presence either of inflammatory epineurial arterial disease or entrapment by neighboring anatomical structures. Skeletal muscle dysfunction may be due to vasculitis, myositis, or denervation atrophy. Both systemic and local anatomical factors, therefore, are of importance in determining the manner in which different parts of the nervous system may be affected in rheumatoid disease. PMID- 6259050 TI - Mesenchymal renal tumors in infancy: a reappraisal. AB - Eight cases of primary mesenchymal renal tumor in infants under one year of age were studied. The patients' ages ranged from one day to seven months; all but one were diagnosed within the first three months of life. There were four typical congenital mesoblastic nephromas. Two malignant mesenchymal, one intermediate case of difficult classification designated as "cellular variant" of congenital mesoblastic nephroma, and one hemangioendothelioma. All patients were alive and free of tumor 3 9/12 to 18 10/12 years after surgery. Of the four infants with congenital mesoblastic nephroma, one was treated by tumor excision alone; nearly 13 years later this patient was free of tumor. A high degree of cellularity and a high nucleus-cytoplasm ratio were features that characterized the tumor diagnosed as "cellular variant" of congenital mesoblastic nephroma. A sarcomatous gross appearance with cavitation necrosis was seen in the two instances of malignant mesenchymal nephroma; one of these metastasized to the lung, whereas in the other, though no metastases developed, all the histologic details of the previous case were reproduced, including distinct foci of necrosis and a high mitosis rate. Mesenchymal renal tumors in young infants constitute a set more heterogeneous than has been previously assumed. They should not be considered uniformly benign. As a group, they span the whole spectrum between benign, morphologically quiescent lesions, clinically and pathologically intermediate or indeterminate ones, and outright malignant tumors with a high risk of distant spread. PMID- 6259051 TI - Morphology of the spleen white pulp in relation to the immunological functions in patients with far advanced bronchial carcinoma. AB - The white pulp of the spleens collected from seventy-nine patients died in far advanced bronchial carcinoma, and the same number of spleens from an age-matched group of patients died in myocardial infarction without evidence of any malignancy was histologically assessed by using a standardized reporting system recently introduced by the author. Emphasis was placed on the evaluation of the cell populations involved in immunological reactions. Histological characteristics suggesting an active function of both the cell-mediated and humoral immune reactions (T- and B-cell areas) were found to be within normal limits in the control series, but profoundly deranged in the cancer patients. Active germinal centers were infrequently seen in both series. The significance of the histological observations made was discussed in the light of the impaired immunological reactivity associated with human malignancies, and a conclusion was drawn, although with some caution, that such an impairment of both the humoral and cell-mediated immune responses might probably exist in a considerable number of the present patients dying of far advanced bronchial carcinoma. The applicability of the reporting system now used for the first time in human pathology was emphasized. PMID- 6259053 TI - Effect of sodium diethyldithiocarbamate on developing embryos of the frog Microhyla ornata. PMID- 6259054 TI - Effects of lethal dose of gamma-irradiation on intestinal enzymes of the pigeons Columba livia intermedia Strickland. PMID- 6259052 TI - Pathological & biochemical changes in the liver & testes of the desert gerbil Meriones hurrianae (Jerdon) : effect of a single intraperitoneal injection of phorate (thimet). PMID- 6259055 TI - Relation of gp70 to spontaneous cytolytic activity of mouse spleen cells. AB - In comparing spleen cells of inbred and congenic mice for spontaneous capacity to lyse cells of the BALB/c leukemia RLmale1 in vitro, we found that the activity of 129 spleen cells was more than double that of 129-Gix- spleen cells. The only known difference between these two strains is that 129-Gix- mice express no known demonstrable gp70 or p30, whereas 129 mice express both these MuLV-related components as mendelian traits not associated with the production of virions. We infer that MuLV-related components at the cell surface are concerned in effector target interactions leading to cytolysis under the conditions described. Although the congenic strains B6 (Gix-) and B6-Gix+ differ likewise in expression of the type-variant Gix-gp70, both strains express a second type-variant of gp70. The lytic activity of spleen cells of these two strains for RLmale1 cells was equally high, suggesting that involvement in lytic effector-target interactions is common to gp70 molecules in general. When used as targets rather than as effectors 129 spleen cells were more sensitive to lysis than 129-Gix- spleen cells. Pre exposure to gp70, purified from R-MuLV, rendered splenic effector cells less lytic. Pre-exposure to gp70 also rendered RLmale1 target cells less sensitive to lysis. One explanation of these findings is that both target cells and effector cells express gp70 and also receptors for gp70 and that this is the basis of mutual cellular recognition leading to lysis in the circumstances described. PMID- 6259057 TI - Evidence for an additional spinal locus of action of clonidine in man. PMID- 6259056 TI - Increased growth of RSV-induced tumors in chickens partially tolerant to MHC alloantigens. AB - Chickens with B2B2 MHC genotypes were made partically tolerant to B5 MHC cell surface antigens and the fate of their Rous-sarcoma-virus (RSV)-induced tumors was determined. B2B2 chickens partially tolerant to viable or lysed white blood cells (WBC) or viable red blood cells (RBC) from B5B5 chickens had a significantly higher incidence of tumor progression than untreated, PBS-treated, or B2B2 chickens inoculated with WBC from other B2B2 chickens. The criteria for tolerance were absence of antibody titer to the cell type inoculated and acceptance of allografts from B5B5 donors by B2B2 chickens. Graft-vs-host reactions occurred only in B2B2 chickens inoculated with viable WBC from B5B5 chickens. It appears that B2B2 chickens partially tolerant to B5 antigens failed to mount a successful immune response to RSV-induced tumors partly because of a B5 MHC antigen(s) cross-reacted with a tumor associated antigen(s) thereby severely limiting B2B2 host recognition of the tumor as foreign. Since WBC and RBC cell-surface antigens appear to contribute similarly to the effect, the B-F- region of the MHC may be involved. PMID- 6259058 TI - Role of kinins in the acute antihypertensive effect of the converting enzyme inhibitor, captopril. AB - The role of kinins in the acute antihypertensive effect of a converting enzyme inhibitor (CEI) was studied in sodium-depleted normotensive and in two-kidney, one clip chronically hypertensive rats (2K-1C). The 2K-1C were on a normal sodium diet. The acute vasodepressor effect of the CEI was determined in these two groups either after administration of normal rabbit globulins or antikinin globulins. The amount of kinin antibodies administered completely blocked the hypotensive effects of bradykinin, 400 ng/kg, and urinary kallikrein, 4 microgram/kg. After administration of CEI in the sodium-depleted rats there was no significant difference (p greater than 0.05) in the acute changes in mean blood pressure (BP) between the group pretreated with normal rabbit globulins (delta BP -32.3 +/- 3.9 mm Hg) and the group pretreated with antikinin globulins (delta BP -25 +/- 2.5 mm Hg). In the 2K-1C pretreated with normal rabbit globulins, the CEI produced a decrease in BP of -21 +/- 4.5 mm Hg. This decrease was almost completely blocked in the group pretreated with the antikinin globulins (delta BP -4 +/- 4.1 mm Hg). These differences in the changes in BP were significant (p less than 0.02). These results suggest that the acute antihypertensive effect of the CEI in the sodium-depleted rats is probably due to inhibition of the conversion of angiotensin I to II while in the 2K-1C it is due, in part, to an increase in kinin concentrations secondary to the inhibition of kininase II. PMID- 6259060 TI - Purification of tonin by affinity chromatography. AB - Tonin has been purified from rat submaxillary glands. The purification procedure included affinity chromatography on Sepharose 4B coupled to antitonin followed by DEAE chromatography and gel filtration on Sephadex G-100. Homogeneity of the purified enzyme was confirmed by Sephadex G-100 gel filtration, disc electrophoresis, and isoelectric focusing on polyacrylamide gel, immunodiffusion, and immunoelectrophoresis. The tonin was purified 11.5-fold, with 35% recovery. The purified tonin has full enzymatic or immunological activity. PMID- 6259059 TI - A possible antihypertensive mechanism of propranolol: antagonism of angiotensin II enhancement of sympathetic nerve transmission through prostaglandins. AB - The effects of propranolol on angiotensin II (AII) enhancement of sympathetic nerve transmission were investigated in the in situ blood-perfused mesenteric vascular bed of the rat. Angiotensin II in subpressor concentrations (3 ng/ml) potentiated the vasoconstrictor responses to both sympathetic nerve stimulation (NS) and exogenous norepinephrine (NE). The dl-propranolol had no effect on the basal vasoconstrictor responses to NS and NE, yet inhibited the AII-enhanced vasoconstrictor responses to NS by 47% (p less than 0.05) and 81% (p less than 0.001) at 100 and 300 ng/ml respectively. In contrast, the potentiation of NE responses by AII was unaffected by propranolol. A similar blockade of AII enhancement of NS was observed with the d-isomer of propranolol. Dibucaine (300 ng/ml), a local anesthetic, failed to alter the basal or AII-enhanced responses to either NS or NE. Indomethacin, a prostaglandin synthetase inhibitor (5 mg/kg, s.c.), abolished the inhibitory effect of dl-propranolol on AII enhancement of NS. Prostaglandin E2 (PGE2), but not prostaglandin I2, (3 ng/ml) inhibited AII enhancement of NS without altering the basal response to NS or NE in indomethacin pretreated animals. Intraarterial infusions of dl-propranolol, d-propranolol, AII, and dl-propranolol-plus-AII into the superior mesenteric artery increased mesenteric venous PGE2 concentrations from 216 +/- 33 to 355 +/- 33 (p less than 0.01), 328 +/- 44 (p less than 0.05), 325 +/- 27 (p less than 0.02), and 407 +/- 44 pg/ml (p less than 0.01) respectively. We conclude that propranolol antagonizes AII enhancement of NS by increasing prostaglandin levels in vascular tissue. Furthermore, these findings suggest that propranolol may exert its antihypertensive effect through the release of prostaglandins when used in therapeutic doses in excess of those required for beta-adrenergic blockade. PMID- 6259062 TI - Calmodulin regulation of testicular cyclic nucleotide phosphodiesterases. AB - Three different, calmodulin-dependent, isoenzymes of cyclic nucleotide phosphodiesterase (PDE) can be isolated by DEAE cellulose chromatography from the immature rat testis and shown to have different substrate specificities and kinetic behaviour. Calmodulin is regulating the activity of these enzymes by altering the maximal velocity (Vmax) rather than the Km of the reaction. Two of the 3 enzymes appear to be testis-specific, while the remaining possesses properties similar to that described for the calmodulin-dependent PDE found in other tissue. PMID- 6259061 TI - Adrenergic neurotransmission in vascular smooth muscle from spontaneously hypertensive rats. PMID- 6259063 TI - Age dependent changes in FSH responsive adenylyl cyclase and FSH binding in rat testes. AB - FSH responsive adenylyl cyclase (AC) activities were examined in both homogenates and membrane particles from 9-71 days old rat testes, and FSH binding was determined in membrane particles from the same animals. FSH responsive AC was measured in the presence of either GTP (0.04 mM) or the non-metabolizable GTP analogue, GMP-P(NH)P (0.04 mM). From days 9 and 11 there was a gradual decrease in both basal and FSH stimulated AC activities and a very similar decrease in FSH binding. The relative stimulation by FSH, however, was fairly constant (2-3 fold stimulation). The excellent correlation between specific FSH binding and FSH responsive AC activities during sexual maturation does not support the notion that uncoupling of the FSH receptors from the AC is a primary reason for the attenuated FSH response during pubertal development. The age dependent decrease in both basal and FSH stimulated AC activities during sexual maturation is a reflection of the relative increase in germ cells (containing no FSH receptors and FSH responsive AC). The LH/hCG responsive AC in membrane particles from the same ages showed an age dependent increase in both absolute activities and relative responses, probably indicating the increased number of Leydig cells in the developing testis. PMID- 6259064 TI - Establishment of a cell line (NPC/HK1) from a differentiated squamous carcinoma of the nasopharynx. AB - A long-term cell culture epithelioid cell line was established from a recurrent squamous carcinoma of the nasopharynx of a Chinese male 17 1/2 years after radiation therapy. The cell line, designated NPC/HK1, has been passed 72 times over a period 1 year. The cells have been shown by light and electron microscopies to be of the squamous epithelial type. When they were transplanted subcutaneously into the back of athymic nude BALB/c (nu/nu) mice, tumors developed at the sites of inoculation, which on histological examination were shown to be well-differentiated squamous carcinomas, similar in morphology to the recurrent human tumor from which they were derived. Karyotypic analysis of cells from the cell line demonstrates an aneuploid human type with a modal chromosome number of 74 with both numerical and structural aberrations. Viral particles or Epstein-Barr viral nuclear antigen (EBNA) has not been demonstrated in the cells from the primary culture or several of the subcultures tested. The presence of EBNA in touch smears prepared from the biopsy tissue was inconclusive. Infection of the subcultured cells with EBV from P3HR1 and B95-8 cells was unsuccessful. PMID- 6259065 TI - Epstein-Barr virus-specific antibody titers in seven Alaskan natives before and after diagnosis of nasopharyngeal carcinoma. AB - Results are presented of Epstein-Barr virus-specific serologic tests for seven Alaskan Native patients with nasopharyngeal carcinoma (NPC) from whom serum had been collected 2-10 years before diagnosis and up to 6 years after diagnosis. The pre-illness antibody spectra and titers of the NPC patients did not differ from those of controls. However, broadened antibody spectra and elevated titers were associated with the emergence of NPC disease, which in one case was present as early as 22 months before actual diagnosis. Increasing or continuously high antibody titers were associated with progression of the disease and death, whereas patients who maintained relatively low, stable antibody titers after treatment have remained well. PMID- 6259066 TI - Epstein-Barr virus-related serology in marrow transplant recipients. AB - Serial sera from 50 marrow transplant recipients were examined for their spectra and titers of antibodies to EBV-specific antigens. Immediately before or after transplant, blood products passively transferred antibodies to EB viral capsid antigen (VCA) and EBV nuclear antigen (EBNA). In most recipients, passively transferred antibodies were replaced by endogenous antibodies regardless of whether donor or recipient had EBV antibodies before transplantation. Commencement or resumption of endogenous EBV antibody production was not associated with signs of infectious mononucleosis or heterophil antibody responses. Antibodies to VCA rose to abnormally high titers, followed successively by antibody to early antigens (EA), and disproportionately low levels of anti-EBNA. Unusually high anti-VCA and anti-EA levels persisted when tests of immune function returned to normal. Antibodies to other herpes group viruses showed no consistent changes. We conclude that (1) EBV does not cause significant clinical problems in marrow transplant recipients; (2) persistent EBV infection can become established or reestablished in the presence of antibodies to EBV; (3) marrow transplant recipients show the same exaggerated immune response to EBV as other immunodeficient patients; and (4) the pattern of EBV specific antibodies may be a more sensitive measure of defective cell-mediated immunity than most conventional tests of immune function. PMID- 6259067 TI - Immunotoxicology of heavy metals. PMID- 6259068 TI - In vitro stimulation of neutrophil motility by metoprolol and sotalol related to inhibition of both H2O2 production and peroxidase mediated iodination of the cell and leucoattractant. AB - The effects of the beta-receptor blockading agents, metoprolol and sotalol on neutrophil random motility, chemotaxis, post-phagocytic glycolysis, superoxide production, hexose monophosphate shunt activity, myeloperoxidase (MPO) mediated protein iodination and hydrogen peroxide production were assessed in vitro. The concentration range investigated was 10(-8)--10(-2) M for each drug. Both agents caused significant stimulation of neutrophil motility at concentrations of more than 10(-4) M. Increased migration was not associated with increased glycolysis or significant cyclic nucleotide fluctuations, but was inversely related to inhibition of superoxide and hydrogen peroxide generation and MPO mediated iodination with both drugs. In a further series of experiments to determine the relationship between the drug induced inhibition of H2O2 production and MPO mediated protein iodination to stimulation of motility it was found that concentrations of sotalol and metoprolol that caused these effects prevented HRP/H2O2/I- induced inactivation of the leucoattractant and inhibition of neutrophil chemotactic responsiveness. Neither drug inhibited the activity of MPO per se nor the reduction of ferricytochrome c by superoxide generated by the xanthine: xanthine oxidase system in vitro. It is suggested that enhanced neutrophil motility is not related to beta-receptor blockade but rather to restricting the availability of hydrogen peroxide and reactive products of the MPO/H2O2/halide system. PMID- 6259069 TI - A prospective clinical study of the mononucleosis syndrome in a developing country. AB - A prospective aetiologic analysis made of 70 children and adults with the clinical and haematologic features of infectious mononucleosis (IM) in Sao Paulo, Brazil, revealed 65.7% due to EBV (31 heterophile antibody positive (HA+), 15 HA negative (HA-) cases), 8.6% due to T. gondii and 4.3% due to CMV. One case was related to viral hepatitis and one to drug hypersensitivity. The other 18.6% were of unknown cause. In the 46 IM cases positive tests were found for EBV/IgM in 93.5%, for heterophile by the absorbed horse Rbc test in 64.2% and by sheep Rbc in 37%. The immune-adherence haemagglutination test was slightly more sensitive than the horse Rbc test in 39 IM sera tested. In 41 EBV/IgM positive sera, EBV/IgA was present in 17/25 containing heterophile antibody and in 2/16 lacking heterophile antibody; anti-EA was present in 85%. The average age of HA+ IM cases was 13.2 years and of HA- cases 4.7 years. Three HA+ and 5 HA- IM cases occurred in the 0-2 year old age group. Few clinical features differentiated between aetiological agents. Exudative tonsillitis was the most helpful one and occurred in 67.7% of HA+ IM cases, 26.7% of HA- cases, in 1 of 3 CMV cases, and not at all in 6 T. gondii infections. PMID- 6259070 TI - Rotavirus and non-bacterial infantile gastroenteritis in Kuwait. AB - The role of rotavirus in non-bacterial gastroenteritis in Kuwait was investigated. Employing electronmicroscopy (EM) and enzyme-linked-immuno-sorbent assay (ELISA) techniques, the virus was detected in the stools of 42 of 274 (15.3%) infants with the disease. A statistically significant association (P less than 0.05) was found between virus excretion and age since 37 of 42 (88.1%) of rotavirus positive cases were aged 2-12 months. 57.1% of all rotaviruses detected were among specimens collected during the first 3 days since onset of clinical symptoms. In addition a highly significant relationship (P less than 0.01) was found between virus excretion and seasonal variation since highest virus excretion rates (76.1%) were detected in specimens collected during the autumn and early winter months, and coincided with the annual gastroenteritis season in Kuwait. Diarrhoea and vomiting were the most frequently encountered clinical symptoms being present in 92.9% and 76.2% of all rotavirus positive patients, respectively. PMID- 6259071 TI - E.s.r. of spin-trapped radicals in gamma-irradiated polycrystalline amino acids, N-acetyl amino acids and dipeptides. AB - The radicals produced in several polycrystalline amino acids, N-acetyl amino acids and dipeptides by gamma-radiolysis at room temperature were investigated by spin-trapping. After irradiation in the solid state, the samples were dissolved in aqueous solutions f t-nitrosobutane and the trapped radicals identified by e.s.r. For alpha-amino acids, deamination radicals were found, and in some cases H-abstraction radicals were also observed. No decarboxylation radicals could be detected. For N-acetyl amino acids, except for N-acetylglycine, the major radical was the decarboxylation radical. For N-acetyglycine the H-abstraction radical from the glycine residue was observed. For dipeptides of the x-glycine, the radical formed by removal of H from the alpha-carbon of the carboxyl-terminal residue was always spin-trapped. Some primary deamination radicals and minor amounts of decarboxylation radicals could also be observed. For dipeptides of the type x-alanine, glycine-x and alanine-x, the decarboxylation radical was always the major spin-trapped radical. Some primary and secondary deamination radicals were also detected. PMID- 6259072 TI - E.S.R. studies of free radicals derived from reaction of OH with uracil and thymine. AB - Short-lived free radicals produced in N2O-saturated aqueous solutions of uracil and thymine have been studied using the in situ radiolysis steady-state e.s.r. method. Radical formed in alkaline aqueous solutions by OH addition to either positions C(5) or (6) were observed. Mechanisms for the formation of transient species were derived. The spin density distribution of the unpaired electron was calculated by means of the INDO method. PMID- 6259073 TI - Radionuclidic studies of ocular blood flow. PMID- 6259074 TI - The Golgi tendon organ. Properties of the receptor and reflex action of impulses arising from tendon organs. PMID- 6259075 TI - [Current aspects of diet therapy of diabetes mellitus]. PMID- 6259076 TI - Intraocular pressure and aqueous flow are decreased by cholera toxin. AB - Delivery of 2.1 microgram of cholera toxin, a specific, irreversible activator of adenylate cyclase, via the blood lowers IOP from 17.4 to 11.2 mm Hg in 81/2 hr. decreases net aqueous flow by about 50% in 8 hr, and doubles blood flow to the anterior uvea at 8 to 13 hr. Intravitreal injection of 0.26 microgram of cholera toxin lowered IOP from 15.0 to 9.6 mm Hg, but heat-inactivated toxin had no effect on IOP. The toxin activates adenylate cyclase from ciliary processes 2.2 fold and stimulates cyclic AMP production by ciliary processes 7.4 times. Absence of aqueous flare, normal protein concentrations in the aqueous, and histologic examination all confirmed the functional and structural integrity of the blood aqueous barrier after cholera toxin infusion. The data point to an important role for ciliary process adenylate cyclase in regulation of aqueous flow and maintenance of IOP. PMID- 6259077 TI - Effects of intravitreal cholera toxin on adenosine 3',5'-monophosphate, intraocular pressure, and outflow facility in rabbits. AB - Catecholamines, prostaglandins, and various hormones may influence aqueous humor dynamics via the second messenger, adenosine 3',5'-monophosphate (cyclic AMP). To test this hypothesis in rabbit ocular tissues, we have investigated the effects of cholera toxin (CTX), a specific, irreversible activator of adenylate cyclase. CTX (5 x 10(-4) to 5 x 10(2) microgram/ml) in both the presence and absence of isobutylmethylxanthine (IBMX) increased cyclic AMP production in the isolated iris-ciliary body. The effects of CTX were dependent on its concentration, duration of exposure, and presence of IBMX. Furthermore, iris-ciliary bodies and scleral-trabecular rings exercised after intravitreal injection of 10 microgram of CTX and incubated in vitro produced significantly more cyclic AMP than contralateral control tissues. Thus significant binding of CTX to both iris ciliary body and scleral-trabecular ring occurred within 5 hr after intravitreal injection. Intraocular pressure (IOP) and outflow facility were measured by intraocular cannulation. Five hours after intravitreal injection of CTX, the IOP was lower than in control eyes. At this time, the outflow facility was threefold greater in the CTX-treated eyes than in control eyes. On the basis of these results, we conclude that (1) CTX stimulates cyclic AMP production in iris ciliary body and scleral-trabecular ring of rabbits, (2) IOP decreases and outflow facility increases after intravitreal injection of CTX, and (3) the hypotensive effect of CTX is apparently mediated, at least partially, by outflow mechanisms. PMID- 6259078 TI - Radiology in inflammatory disease of the colon: an area of increased interest for the modern clinician. PMID- 6259079 TI - Effect of urine concentration versus tissue concentration of ampicillin and mecillinam on bacterial adherence in the rat bladder. AB - We investigated the effect of tissue and urine concentrations of ampicillin and mecillinam on bacterial bladder wall adherence in rats. Escherichia coli 02 labeled with 3H-1-leucine was inoculated into the bladder for 2 hr. With the ureters transected bilaterally, antibiotic was instilled into the bladder lumen or administered intravenously only. No bacteria survived after the presence of antibiotic in the bladder lumen for 1.5 hr. After intravenous administration of ampicillin, with no antibiotic in the bladder lumen, measured by viable counts, decreased significantly as compared to controls. Adherence, measured by radioactive counts, decreased significantly after intravenous administration of mecillinam, possibly indicating prevention of tissue invasion. This finding was explained by entrapment of bacterial debris in the bladder lumen and invasion of bacteria into the bladder wall. Our results support the importance of tissue concentrations in the treatment of urinary tract infections. PMID- 6259080 TI - Tissue disaggregation of human kidney cells followed by purification on isokinetic and isopyknic gradients. AB - Five normal human kidneys were disaggregated with three combinations of enzymes. The combination of collagenase 0.5 mg per ml of 11 additional kidneys. The viability of cells in suspension ranged from 75 to 94 per cent with a mean viability of 85.3 +/- 1.6 per cent. Disaggregated kidney cells were fractionated in isopyknic and isokinetic gradients. After isokinetic sedimentation, kidney tubule cells were predominantly in fraction 22 +/- 1 whereas lymphocytes were consistently located in fraction 8 +/- 1. Kidney epithelial cells were enriched to a 90.4 +/- 2.2 per cent (79.0 to 96.0 per cent) purity by isokinetic gradient centrifugation. Controlled rate freezing of cells provided material for repeated experiments, and short-term tissue culture before cell separation increased the proportion of viable cells in suspension. PMID- 6259081 TI - Occurrence, transplantation, and histologic characteristics of nephroblastoma in the Nb hooded rat. AB - Ten kidney tumors conforming to nephroblastoma were encountered during a 10-year period in a closed colony of Nb hooded rats. Histologic examination of the primary neoplasms, and of a limited number of transplanted derivatives, indicates that spontaneous nephroblastoma in the rat is exclusively an epithelial neoplasm, consisting of dense aggregates of undifferentiated, basophilic blast cells set in a connective tissue stroma of benign character. This uniform entity should be clearly distinguished from renal mesenchymal tumor, a connective tissue neoplasm of heterogeneous form which is induced frequently in rats by certain chemical carcinogens. PMID- 6259082 TI - Orientation of structural polypeptides of equine infectious anemia virus. AB - Lactoperoxidase iodination of intact and disrupted equine infectious anemia virus revealed that glycopeptide gp79 is the major surface component of this virus, whereas glycopeptides gp64 and gp40 as well as the principle nonglycosylated structural polypeptides p29 and p13 are internal. Virus 'envelope' particles, banding in isopycnic centrifugation at approximately 1.10 g/cm3, contained the glycopeptides but no internal nonglycosylated proteins. Glycopeptides gp79, gp64 and gp40 and core polypeptide p29 were isolated by SDS-PAGE, iodinated in vitro, and compared by two-dimensional tryptic peptide analysis. Tryptic digests of the glycopeptides were similar but distinct from that of p29. PMID- 6259083 TI - Expression of type-common envelope antigens by herpes simplex virus type 2 transformed hamster cells. AB - At least ten polypeptides were detected on the surface of the herpes simplex virus type 1 (HSV-1) virion. Two of these polypeptides, having molecular weights of 30,000 and 33,000, were identified in two herpes simplex virus type 2 transformed cell lines (333-8-9 and 333-2-29) by immunoprecipitation and SDS PAGE. The same two virion polypeptides previously were shown to be present in an HSV-1-transformed cell line (14-012-8-1, T-10). These observations suggest that genetic information coding for these polypeptides is in close proximity to that portion of the virus genome involved in transformation. PMID- 6259084 TI - Reversible inhibition of cytomegalovirus replication by phosphonoformate. AB - Cytomegalovirus (CMV Ad. 169)-induced late antigens are specifically inhibited by phosphonoformate (PFA). Four fresh isolates of CMV were also inhibited by PFA to varying degrees. The kinetics of CMV immediate early antigens (IEA) and early nuclear antigens (EA) produced in the presence of PFA were compared to the early phase of the replicative infection. After anticomplement immunofluorescence with anti-IEA and anti-EA, microimmunofluorometry of individual CMV-infected nuclei was performed. CMV-induced antigens had a two-wave appearance, with maxima at 6 and 24 h postinfection. The same was seen in the presence of PFA. CMV EA containing cells persisted for more than 5 weeks in the presence of PFA, but decreased in frequency and antigen content. The inhibition of virus replication was reversible after all incubation periods assayed. After PFA release, IEA and EA appeared again in many cells, and the kinetics were similar to that of initial infection. The results suggest that the input CMV genome persists in most initially infected cells, survives PFA incubation, and is active again after PFA release. This differs from abortive CMV infections. PMID- 6259085 TI - Identification of permissive and nonpermissive murine cells for polyoma virus. AB - The interaction of polyoma virus with primary cell cultures derived from mouse heart, brain, and kidney was characterized to identify the organ(s) best suited for isolation of permissive and nonpermissive cells within a species. The outcome of infection was determined by measurement of the extent of cellular destruction, virus amplification, and viral gene expression. While the majority of cells in the kidney cultures were permissive, the heart cell cultures contained a significant population of nonpermissive cells. PMID- 6259086 TI - Nomenclature of flavivirus-specified proteins. AB - Flavivirus structural proteins are designated E, C, and M, replacing the former nomenclature of V3 (envelope), V2 (core), and V1 (membrane-like) proteins, respectively. The nonstructural proteins, formerly NV1 through NV5, are designated by their apparent size in kilodaltons, prefixed by P (or GP if a glycoprotein), if they are stable unrelated end-products; the lower case p or gp is used for variants or uncharacterized products. A relationship to any structural protein is indicated by adding E, C, or M parenthetically to the designation of the appropriate nonstructural protein. PMID- 6259087 TI - Transplacental infection with adeno-associated virus type 1 in mice. AB - Adeno-associated type 1 parvovirus (AAV) was detected in the kidneys and lungs of fetuses and newborns, when pregnant mice were injected subcutaneously with AAV type 1 and murine adenovirus as a helper virus. These findings clearly indicate that transplacental infection with AAV in rodents has been achieved. PMID- 6259089 TI - [Results of curative, distal resection of stomach neoplasms]. AB - Between 1962 and 1971 there were operated 99 patients suffering from gastric cancer. From these, 83% could be controlled as long-term follow-up. The overall survival rate after one year was 68%, after three years 40% and after five years 36%. The patients with tumor-free lymph nodes showed a 5-year survival rate of 49% while of those with tumor-involved lymph nodes only 17% lived longer than five years. The survival rate, especially of older patients (above 60 years), showed with a distal gastric resection compared to a total gastric resection a significant lower postoperative mortality, a better quality of life and a better survival rate. A total gastric resection should only be indicated in cases in which a radical tumor resection could not be realized with a distal gastric resection. PMID- 6259088 TI - Release of rat liver endoplasmic reticulum membrane proteins into the cytosol. AB - A membrane-free supernatant is prepared from rat liver cell homogenate by centrifugation at 230,000 x g. AMPase, NADH- and NADPH-cytochrome c reductase activities are demonstrated in the supernatant. These enzymes can be released from rough microsomal membranes by incubation in 0.25 M sucrose at 37 degrees C for 30 minutes. This release is time and temperature dependent and decreases in presence of phospholipase inhibitors. These results indicate that transfer of membrane enzymes from membranes to the cytosol may take place also in vivo. The process seems to be due to an enzymatic digestion of membranes and may be a mechanism for membrane turnover in addition to autophagocytosis. PMID- 6259090 TI - [Management of liver cell adenoma and focal nodular hyperplasia]. AB - Since 1975 six cases with hepatic adenoma (5 females, 1 male) and five cases with focal nodular hyperplasia (3 females, 2 males) have been treated at our hospital. Four of the five women with hepatic adenoma took oral contraceptive pills before the diagnosis was made, only one patient took the pills in the group with focal nodular hyperplasia. Hepatic adenomas were resected electively in three patients; one patient underwent operation because of ruptureed adenoma with intraabdominal hemorrhage. In the other two cases with hepatic adenoma resections were not possible, but both tumors have regressed after the cessation of oral contraceptives. One patient in the group with focal nodular hyperplasia underwent liver resection because of intratumoral hemorrhage with recurrent pain; in the other four cases no treatment was done as symptoms were absent. We recommend elective resection for hepatic adenoma because of the high risk of spontaneous ruptur. Embolization or ligation of the hepatic artery are alternative procedures when resection is not possible and tumors do not regress after the cessation of oral contraceptives. On the other hand a more conservative attitude is suggested for focal nodular hyperplasia because those patients do not frequently bleed; resection is indicated in case of symptoms or growth of tumor. PMID- 6259091 TI - Hemoglobin Hammersmith (beta 42 (CD1) Phe replaced by Ser) associated with severe hemolytic anemia. AB - Hemoglobin Hammersmith was detected in a five year old white female suffering from severe anemia first noted at 18 months of age. She has been splenectomized and her peripheral blood red cells were found to contain inclusion bodies. PMID- 6259092 TI - [Liver cell carcinoma following juvenile acute lymphoblastic leukemia. Case contribution]. AB - The case history of a boy suffering from acute lymphoblastic leukemia (ALL) and carcinoma of the liver as secondary malignoma is reported. After completion of the combined ALL-therapy, a splenogenous thrombocytopenia emerged which was successfully treated by splenectomy. In the biopsy material liver cirrhosis and HBsAg-positive hepatitis could be detected; these proved to be progressive in the course of the following year. At the end of another year, a hepatocellular carcinoma was diagnosed, causing the patient's death, who was still in complete hematological remission 5 7/12 years after the onset and 2 9/12 years after the end of the ALL-therapy. Only two cases of hepatocellular carcinoma following ALL in childhood have been described in the literature so far. PMID- 6259093 TI - Symbrachydactyly: pathogenesis of 5-fluorouracil induced model in mice. PMID- 6259094 TI - Optimum dose of radiotherapy for chemodectomas of the middle ear. PMID- 6259096 TI - What is the optimum dose of radiation therapy for glomus tumors? PMID- 6259095 TI - Choriocarcinoma: a success story for chemotherapy. PMID- 6259097 TI - Cardiac responses to exercise training in male and female rats. AB - The purpose of the present study was to determine if contractile function adapts to physical training in the same way in hearts of male and female rats. Male and female rats were trained with a running program sufficient to cause equal increases in cytochrome oxidase activity in gastrocnemius muscles in both groups. Hearts were then studied in an isolated perfused working rat heart apparatus with varying preloads and fixed afterloads. Five groups were studied: 1) free-eating sedentary males (MS-FE); 2) running males (MR); 3) sedentary females (FS); 4) running females (FR); and 5) food-restricted sedentary; males (MS-FR). Heart weights were similar in MS-FE and MR and in FS, FR, and MS-Fr. Stroke work, stroke volume, coronary flow, and myocardial oxygen consumption were significantly higher in MR than in MS-FE but were almost identical in FR and FS. MS-FR showed stroke work, stroke volume, and ejection fractions that were similar to MR but higher than MS-FE and both female groups. Thus when hearts of equal weights were compared, a training effect was only seen in males. These results suggest that despite similar skeletal muscle adaptations, hearts of male rats adapt to physical training by running with improved intrinsic performance, whereas hearts of female rats do not. PMID- 6259098 TI - Lipolysis and cAMP accumulation in adipocytes in response to physical training. AB - Adenylate cyclase activity is lower in membrane preparations of fat cell homogenates from exercise-trained compared with sedentary rats (J. Appl. Physiol.: Respirat. Environ, Exercise Physiol. 42: 884-888, 1977). In the present investigations lipolysis and cyclic adenosine 3':5'-monophosphate (cAMP) accumulation were measured in isolated parametrial fat cells prepared from sedentary and trained rats. The purpose of these investigations was to determine whether the normal catecholamine-induced increases in cAMP accumulation is affected in isolated adipocytes from endurance-trained rats. The increases in cAMP accumulation in response to isoproterenol (0.01-10 microM) was reduced in fat cells isolated from trained rats. However, glycerol release in response to the same hormonal challenge was greater in these adipocytes. cAMP phosphodiesterase activity measured at 0.125 and 1.025 microM cAMP was greater in the particulate fraction of fat cell homogenates obtained from trained rats as compared with their sedentary counterparts. Hormone-sensitive lipase activity was reduced in crude fat pad homogenate preparations from trained rats if the animals were killed at rest. However, if the animals were run to exhaustion immediately prior to being killed, there were no differences in the hormone-sensitive lipase activity between preparations from trained and nontrained rats. These data indicate that, although cAMP accumulation by isolated fat cells in response to isoproterenol is markedly lower in trained rats, lipolysis and hormone-sensitive lipase activation is not reduced. PMID- 6259099 TI - Exercise and the cAMP system in rat adipose tissue. I. Lipid mobilization. AB - Protein kinase (PK) and hormone-sensitive lipase (HSL) were measured at rest in adipose tissue of untrained male rats and in that of animals subjected to a strenuous program of treadmill running. Total amounts of PK activity (decreased from 860 +/- 104 to 474 +/- 53 pmol.min-1. (10(6) cells)-1 (P less than 0.01) as a result of exercise training. At the same time, binding capacity for adenosine 3',5'-cyclic monophosphate (cAMP) was elevated in the runners. These data suggest a functional loss in catalytic activity without a loss in binding capacity. In addition, the results provide evidence that the capacity of PK to activate HSL is reduced in adipocytes of physically trained rats. HSL activity was measured in both adipose tissue slices and isolated adipocytes. The results show that the levels of activity of HSL did not increase as a result of the running program. These results provide evidence that the lipolytic capacity of adipocytes of normal untrained male rats is sufficiently large to meet the increased demand for free fatty acids imposed by the exercise program without the need for an adaptive increase in HSL activity. PMID- 6259100 TI - Exercise and the cAMP system in rat adipose tissue II. Nucleotide catabolism. AB - In this study the effect of exercise training on the adenosine 3',5'-cyclic monophosphate (cAMP) system of rat adipose tissue has been investigated. The basal amount of cAMP for the exercising rats was 0.179 +/- 0.021 nmol/10(6) cells, the same value as for the controls. Phosphodiesterase activities (low and high Km) remained unaffected as a result of the program of treadmill running. Kinetic constants for the low- and high-Km phosphodiesterases revealed that the affinity of the enzymes for substrate (cAMP) was unaltered by physical training. Finally, ethyleneglycol-bis(beta-aminoethylether)-N,N'-tetraacetic acid, possibly through its effect on calmodulin, stimulated or inhibited (depending on concentration) phosphodiesterase activity in the same direction and to a similar extent in extracts of adipose tissue from runners and controls. Taken together, these data clearly demonstrate the exercise training has no effect on the cAMP system of adipose tissue in male rats. PMID- 6259101 TI - Effects of hypoxia on density of beta-adrenergic receptors. AB - Exposure to chronic hypoxia results in a lower resting heart rate and a blunted cardiovascular responsiveness to beta-adrenergic receptor stimulation. Possible effects of acclimatization to high altitude on the binding of [125I]iodohydroxybenzylpindolol to beta-adrenergic receptors on membranes of right and left ventricles of rat heart were determined. Chronic high-altitude exposure led to a decrease in the density of beta-adrenergic receptors in nonhypertrophied left ventricles as well as in hypertrophied right ventricles. The affinity of the receptor for the radioligand was not changed by the exposure to high altitude, suggesting that the properties of the receptor were not affected. Basal and isoproterenol-stimulated adenylate cyclase activities were decreased in membranes prepared from hearts and pulmonary arteries of rats acclimatized to high altitude. The loss of cardiac beta-adrenergic receptors in rats adapted to high altitude was prevented by the chronic coadministration of a low dose of DL-propranolol. The results suggest that changes in beta-adrenergic receptor density may partially explain the hemodynamic adaptation that occurs with chronic hypoxia. These decreases may be due to a loss of functional beta adrenergic receptors caused by chronically elevated concentrations of circulating neurally released catecholamines. PMID- 6259102 TI - Inhibitory innervation to the guinea pig trachealis muscle. AB - The inhibitory innervation of the cervical trachea was studied in situ in anesthetized male guinea pigs. We measured effects of electrical stimulation of vagal motor and sympathetic trunk nerve fibers, during atropine, on trachealis muscle tension. Effects of direct transmural stimulation of trachealis muscle were also determined. We confirmed the dual nature of the inhibitory innervation to this muscle. Vagal motor inhibitory nerves are shown to be preganglionic. Neural transmission at the level of the ganglia is characterized by filtering of high frequency action potentials. The neurotransmitter at the myoneural junction is unidentified but is not norepinephrine. Maximal relaxation accounts for about 20-40% of maximal relaxations seen with transmural stimulation of trachealis muscle in the presence of atropine. Sympathetic trunk nerve fibers are also preganglionic. Neurotransmission at the level of the ganglia is apparently 1:1 at high-action potential frequencies. Norepinephrine released presynaptically has access to smooth muscle beta- but not alpha-receptors. Maximal adrenergic relaxations account for 60-80% of total transmural stimulation relaxations. Transmural stimulation relaxations appear to be accounted for by release of neurotransmitter from sympathetic adrenergic plus vagal nonadrenergic postganglionic nerve fibers. PMID- 6259103 TI - Writing across the curriculum. PMID- 6259104 TI - Seminar in communication with deaf clients: a nursing elective to assist students in meeting the needs of a special population. PMID- 6259105 TI - Characteristics contributing to attachment behavior and its outcomes in student nurse-family relationships. PMID- 6259106 TI - Pathophysiology content in baccalaureate programs. PMID- 6259107 TI - Effective integration of health education into baccalaureate nursing curriculum. AB - Under the auspices of the Division of Health Education at the School of Hygiene and Public Health and in conjunction with George Mason University, Department of Nursing, a Project is underway to develop, implement and test a model which incorporates appropriate health education learning into baccalaureate nursing education. The underlying premise of the Project is that nurses who are able to formulate theoretically sound educational programs in conjunction with clients and fellow providers will be more effective in achieving health education outcomes. Our hope is that this will increase the competence and confidence nurses have in helping others cope productively with the real and potential health threats confronting them. PMID- 6259108 TI - Nursing homes for the initial clinical experience. PMID- 6259109 TI - Communication skills: an adjunct to the nursing curriculum. PMID- 6259110 TI - Academic procedural due process for students in the health professions. PMID- 6259111 TI - Etiology of malignant catarrhal fever. PMID- 6259112 TI - Caprine arthritis-encephalitis: clinical features and presence of antibody in selected goat populations. AB - Features of caprine arthritis-encephalitis, a retrovirus disease of domestic goats, were studied in 60 goats over a 10-year period. The rate of progression and the severity of the disease process were highly variable within and among animals, but the most salient features were chronically swollen joints and bursae, lameness, weight loss, poor coat, mineralization of soft tissue, and death. Of 1,160 goat serum samples from 24 states tested by the immunodiffusion technique, 81% were positive for antibody to caprine arthritis-encephalitis virus antigens. PMID- 6259113 TI - Prophylaxis of kanamycin-induced ototoxicity by a radioprotectant. AB - S-2 (3-aminopropylamino)ethylphosphorothioate ameliorates hearing losses due to ototoxic doses of kanamycin sulfate in the guinea pig when administered one hour before the antibiotic. Since this radioprotectant is believed to operate as a free-radical scavenger, kanamycin ototoxicity may involve free radicals. PMID- 6259114 TI - Acid digestion determination of iodine in foods. AB - A method for determining iodine in food is described. The samples were digested using a mixture of sulfuric, nitric, and perchloric acids. The iodine was determined by an automated colorimetric method based on the iodide-catalyzed reduction of Ce+4 by As+3. For milk samples, the relative standard deviation for the method was less than 3%, and the recovery of 125I added to milk and carried through the method ranged from 96 to 102%. The method was compared with 4 other procedures and was superior to alkaline dry ashing methods. PMID- 6259115 TI - Role of nucleases in the isolation of plasmid deoxyribonucleic acid from Pseudomonas cepacia 4G9. AB - Brij 58-cleared lysates of Pseudomonas cepacia 4G9 contain both exonucleolytic and endonucleolytic activities. Endonuclease activity was unaffected by 125 mM ethylenediaminetetraacetic acid, whereas the exonuclease activity was inhibited. In contrast, Sarkosyl NL97 inhibited only the endonuclease. Sodium dodecyl sulfate inhibited all nuclease activity in in vitro assays, but plasmid deoxyribonucleic acid added to P. cepacia 4G9 spheroplasts during sodium dodecyl sulfate lysis was degraded. Irreproducible plasmid isolation from P. cepacia 4G9 may be due to this nucleolytic activity. PMID- 6259117 TI - Plasmid-mediated resistance to aminocyclitol antibiotics in group D streptococci. AB - Streptococcus faecalis BM4100 was resistant to high levels of gentamicin, kanamycin, and structurally related antibiotics. The genes conferring resistance to aminocyclitols in this strain were carried by a plasmid, pIP800, self transferable to other S. faecalis strains. The aminocyclitol resistance was mediated by constitutively synthesized phosphotransferase and acetyltransferase activities. It was inferred that phosphorylation occurred at the 2"-hydroxyl group and that acetylation occurred at the 6'-hydroxyl group of the aminocyclitols. The enzyme activities were not separable by gel filtration or by isoelectric focusing. Their apparent molecular weight was 31,000, and their isoelectric point was 5.3. With respect to substrate profile, size, and charge, the transferases from strain BM4100 resembled closely those with identical site specificity described in staphylococci. These results suggest that plasmid gene transfer may occur between the two pathogenic bacterial genera. PMID- 6259116 TI - Isolation and Characterization of acetate kinase and phosphotransacetylase mutants of Escherichia coli and Salmonella typhimurium. AB - Mutations in the ack (acetate kinase) and pta (phosphotransacetylase) genes in Salmonella typhimurium were characterized and determined to be analogous to those of previously described Escherichia coli mutants. We established that in both bacterial species these genes were cotransducible with the neighboring histidine transport operon and were distally located relative to purF. pta mutants were sensitive to the dye alizarin yellow and were unable to grow on medium containing inositol as a carbon source. We selected mutants of both species with deletions covering both the ack and the pta genes; some deletions extended into the histidine transport operon. PMID- 6259119 TI - Specificity in the formation of delta tra F-prime plasmids. AB - Twenty-three independent delta tra F-prime plasmids from three different Escherichia coli K-12 sublines were isolated from Hfr strains whose points of origin coincided with the IS3 element alpha 3 beta 3 or alpha 4 beta 4 in the lac purE region of the E. coli chromosome. Electrophoretic analysis of plasmid deoxyribonucleic acid digested with EcoRI and hybridization analysis of plasmid deoxyribonucleic acid digested with BglII revealed that at least 14 of these plasmids were formed by processes involving specific bacterial and F loci. Two of the specific bacterial loci involved in delta tra F-prime formation were located at approximately 3.3 and 11.7 min on the E. coli chromosomal map. Two of the delta tra F-prime plasmids contained bacterial deoxyribonucleic acid with circularization endpoints that mapped very near the termini of the IS2 element that is normally located between lac and proC. PMID- 6259118 TI - Regulation of carbamylphosphate synthesis in Serratia marcescens. AB - Serratia marcescens HY possessed a single carbamylphosphate synthase (CPSase) which was subject to cumulative repression by arginine and a pyrimidine. CPSase did not appear to be a part of a multifunctional enzyme complex as is the case for other enzymes of pyrimidine biosynthesis in this organism. CPSase was purified to homogeneity. The molecular weight of the enzyme was estimated to be 167,000 by sucrose density gradient ultracentrifugation. The double-reciprocal plot for magnesium adenosine triphosphate was linear, yielding a Km value of 2.5 mM. The enzyme utilized either glutamine (Km, 0.1 mM) or NH3 (Km, 10.5 mM) as a nitrogen donor in the reaction. CPSase activity was subject to activation by ornithine and feedback inhibition by uridine monophosphate, as is the case for other enteric bacteria. Carbamate kinase activity, detected in crude extracts of S. marcescens, was shown to be due to a constitutive acetate kinase. The absence of carbamate kinase from S. marcescens HY is consistent with the inability of this organism to utilize arginine as a source of energy under anaerobic conditions. PMID- 6259120 TI - Correlation between acrasins and spore germination inhibitors in cellular slime molds. AB - Discadenine,3-(3-amino-3-carboxypropyl)-N6-delta 2-isopentenyladenine, which inhibits spore germination, was previously found in Dictyostelium discoideum. Studies on the distribution of discadenine in different species of cellular slime molds by high-pressure liquid chromatography showed that discadenine is present in D. discoideum, Dictyostelium purpureum, and Dictyostelium mucoroides, but not in Dictyostelium minutum, Polysphondylium violaceum, or Polysphondylium pallidum. Discadenine synthetase, which is involved in biosynthesis of discadenine with N6 delta 2-isopentenyladenine as substrate, was only detected in cells of the former three species. In addition, discadenine inhibited spore germination only in these three species. These results clearly demonstrate that discadenine is produced as an inhibitor of spore germination in the species of cellular slime molds in which the acrasin is cyclic adenosine 5'-monophosphate (AMP). This means that there is a structural and biochemical correlation between the spore germination inhibitor and the acrasin, since 5'-AMP, a direct precursor in discadenine biosynthesis, can be derived from cyclic AMP by hydrolysis with cyclic AMP phosphodiesterase. PMID- 6259121 TI - Molecular cloning, correlation of genetic and restriction maps, and determination of the direction of transcription of gnd of Escherichia coli. AB - Expression of the gene gnd of Escherichia coli, which encodes 6-phosphogluconate dehydrogenase, is regulated by growth rate. Using deoxyribonucleic acid from the specialized transducing phage lambda h80 dgnd his as the source of gnd, we cloned restriction fragments carrying the complete gene and portions of it on the plasmid vector pBR322. A hybrid plasmid carrying a 3.7-megadalton HindIII restriction fragment from the phage was prepared and found to be gnd+. Through restriction mapping of this fragment and subcloning segments of it, we prepared a gnd+ hybrid plasmid which carried only 1.85 megadaltons of E. coli deoxyribonucleic acid. A cleavage site for the restriction endonuclease PstI was located on the genetic map of gnd by cloning adjacent EcoRI-PstI restriction fragments and crossing the resulting hybrid plasmids with previously mapped gnd deletion and bacteriophage Mu insertion mutants. A maxicell experiment was used to determine the direction of transcription of gnd, to identify which EcoRI-PstI fragment contains the gnd promote, and to localize th beginning of the structural gene to a region about 850 +/- 150 base pairs from the PstI cleavage site. A fine structure restriction map surrounding the PstI cleavage site was prepared for endonucleases KpnI, HincII, HaeIII, HpaII, and TaqI. PMID- 6259122 TI - Restriction map of the Escherichia coli malA region and identification of the malT product. AB - A series of plaque-forming lambda h80 transducing phages carrying various portions of the malA region were isolated. A 5,800-base pair HindIII-EcoRI DNA fragment from one of these phages was cloned into pBR322 and shown to contain malT, which is the positive regulator gene of the maltose regulon, and most of malP, the structural gene for maltodextrin phosphorylase. A restriction map of the HindIII-EcoRI fragment was established, and it was correlated with the genetic map of the malA region (i) by mapping deletions which had been generated in vitro on the plasmid and (ii) by locating on the restriction map a DNA insertion of known genetic position. A 600-base pair HincII-HaeII segment was shown to contain all or part of the promoters for malT and malP, which are known to be transcribed in opposite directions. Strains carrying gene malT on a plasmid synthesized a 94,000-dalton polypeptide which was not produced by identical strains carrying similar plasmids in which malT was partially deleted. Estimates of the size of the malT gene support the conclusion that the 94,000-dalton polypeptide is the malT product. PMID- 6259123 TI - Hemolysis determinant common to Escherichia coli hemolytic plasmids of different incompatibility groups. AB - By using cloned deoxyribonucleic acid fragments from the hemolysis determinant of the hemolytic plasmid pHly152 as hybridization probes, a deoxyribonucleic acid segment of about 3.8 megadaltons was identified as a common sequence in several hemolytic (Hly) plasmids of Escherichia coli belonging in four different incompatibility groups. This segment contained the genetic information for the synthesis and secretion of the extracellular toxin alpha-hemolysin of E. coli. With the exception of pSU5, representing a composite plasmid, one part of which seems to be very similar to pHly152, the overall sequence homology of these Hly plasmids with pHly152 seems to be rather restricted. However, the Hly plasmid pSU316 showed sequence homology with pHly152 that did not extend beyond the hemolysis determinant. The two other plasmids, pSU233 and pSU105, also shared homology with pHly152 in the hemolysis determinant as well as in various other parts of this plasmid which did not seem to be directly linked to the hemolysis determinant. This suggests that the hemolysis determinant has spread to presumably unrelated plasmids of E. coli. PMID- 6259124 TI - Cloning of gene lon (capR) of Escherichia coli K-12 and identification of polypeptides specified by the cloned deoxyribonucleic acid fragment. AB - A mutation in the lon (capR) gene of Escherichia coli K-12 results in overproduction of capsular polysaccharide and increased sensitivity to ultraviolet and ionizing radiations. The lon (capR) gene deoxyribonucleic acid was cloned from a new F' factor. The new plasmids, designated pBZ201 and pBZ203, (i) contained an additional 8.2-megadalton (Md) EcoRI fragment that had the same mobility as one of the EcoRI fragments of the F', and (ii) conferred repression of capsular polysaccharide synthesis and repression of sensitivity to ultraviolet radiation in a bacterial transformation experiment with capR mutant recipient strains. A capR9 mutant plasmid, pBZ201M9, was also isolated and conferred expression of mucoidy and ultraviolet sensitivity to a capR(+) (lon(+)) strain, indicating that the capR9 allele was dominant. Plasmids pBZ201M80, pBZ201M9-INSA, and pBZ201M9-INSB were characterized by transformation as containing recessive capR mutant alleles. Heteroduplex analyses and agarose gel electrophoresis of restriction endonuclease digests of plasmid DNA preparations revealed that (i) pBZ201M9-INSA and pBZ201M9-INSB each contains a 0.5-Md insertion (probably IS1) in the cloned DNA fragment at the same site, and (ii) pBZ201 and pBZ203, both capR(+) plasmids, contain the same 8.2-Md fragment cloned in opposite orientations with respect to the cloning vehicle, pSC101. Plasmid-specified polypeptides were determined by using strain CSR603 maxicells containing each plasmid. Two new polypeptides were coded by the lon(+) (capR(+)) 8.2-Md DNA fragment: Z1, 94 kilodaltons (94K), and Z2, 67K. The maxicells containing recessive capR mutant plasmids were deficient only in synthesis of the 94K polypeptide, and the dominant (capR9) mutant plasmid specified 5 to 10 times more of the 94K polypeptide than the maxicells containing the capR(+) plasmid. Other data indicated that the capR9-specified "94K polypeptide" was not identical to the capR(+)-specified "94K polypeptide." Thus the altered mutant polypeptide was synthesized in increased quantities, suggesting a defective mode of autogenous regulation for the capR9 polypeptide and effective autogenous regulation of the capR(+) polypeptide. PMID- 6259125 TI - Outer membrane protein H1 of Pseudomonas aeruginosa: involvement in adaptive and mutational resistance to ethylenediaminetetraacetate, polymyxin B, and gentamicin. AB - It is well established that Pseudomonas aeruginosa cells grown in Mg2+-deficient medium acquire nonmutational resistance to the chelator ethylenediaminetetraacetate and to the cationic antibiotic polymyxin B; this type of resistance can be reversed by transferring the cells to Mg2+-sufficient medium for a few generations. Stable mutants resistant to polymyxin B were isolated and shown to have also gained ethylenediaminetetraacetate resistance. Both the mutants and strains grown on Mg2+-deficient medium had greatly enhanced levels of outer membrane protein H1 when compared with the wild-type strain or with revertants grown in Mg2+-sufficient medium. It was determined that in all strains and at all medium Mg2+ concentrations, the cell envelope Mg2+ concentration varied inversely with the amount of protein H1. In addition, the increase in protein H1 in the mutants was associated with an increase in resistance to another group of cationic antibiotics, the aminoglycosides, e.g., gentamicin. We propose that protein H1 acts by replacing Mg2+ at a site on the lipopolysaccharide which can otherwise be attacked by the cationic antibiotics or ethylenediaminetetraacetate. PMID- 6259126 TI - Positive selection for loss of tetracycline resistance. AB - A simple technique has been devised that allows direct plate selection of tetracycline-sensitive clones from a predominantly tetracycline-resistant population. The technique is especially useful in genetic methodologies based on the use of tetracycline resistance transposons, such as Tn10. Potential uses of the method include selection of deletion mutants, fine-structure mapping, generalized mapping, construction of multiply marked strains, elimination of tetracycline resistance transposons and plasmids and cloning. The technique is based on our finding that tetracycline-resistant cells are hypersensitive to lipophilic chelating agents, such as fusaric acid. This finding supports the contention that certain metal ions critically facilitate tetracycline uptake and leads us to suggest possible molecular mechanisms for tetracycline resistance. PMID- 6259128 TI - Purification and characterization of cytidine 5'-triphosphate:cytidine 5' monophosphate-3-deoxy-D-manno-octulosonate cytidylyltransferase. AB - Cytidine 5'-triphosphate:cytidine 5'-monophosphate-3-deoxy-D-manno-octulosonate cytidylyltransferase (CMP-KDO synthetase) was purified 2,300-fold from frozen Escherichia coli B cells. The enzyme catalyzed the formation of CMP-KDO, a very labile product, from CTP and KDO. No other sugar tested could replace KDO as an alternate substrate. Uridine 5'-triphosphate at pH 9.5 and deoxycytidine 5' triphosphate at pH 8.0 and 9.5 could be used as alternate substrates in place of CTP. CMP-KDO synthetase required Mg2+ at a concentration of 10.0 mM for optimal activity. The pH optimum was determined to be between 9.6 and 9.3 in tris(hydroxymethyl)aminomethane-acetate or sodium-glycine buffer. This enzyme had an isoelectric point between pH 4.15 and 4.4 and appeared to be a single polypeptide chain with a molecular weight of 36,000 to 40,000. The apparent Km values for CTP and KDO in the presence of 10.0 mM Mg2+ were determined to be 2.0 X 10(-4) and 2.9 X 10(-4) M, respectively, at pH 9.5. Uridine 5'-triphosphate and deoxycytidine 5'-triphosphate had apparent Km values of 8.8 X 10(-4) and 3.4 X 10(-4) M. respectively, at pH 9.5. PMID- 6259127 TI - Reexamination of the genome size of myxobacteria, including the use of a new method for genome size analysis. AB - The genome sizes of two myxobacteria, Myxococcus xanthus and Stigmatella aurantiaca, were measured by renaturation analysis and also by a new method involving the quantitation of individual restriction fragments. In contrast to several previous reports, which indicate that M. xanthus has a genome size which is three to four times that of Escherichia coli, the present measurements indicated that the M. xanthus genome is only about 24 to 53% larger than that of E. coli. S. aurantiaca had a genome size nearly identical to that of M. xanthus. Of possible significance is the fact that the renaturation curves of M. xanthus and S. aurantiaca deoxyribonucleic acid both exhibited significant fractions which renatured with rapid, unimolecular kinetics. However, we were unable to establish that these fractions represented inverted repeats of repetitive sequences. PMID- 6259129 TI - Cyclic adenosine 3',5'-monophosphate levels in Pseudomonas putida and Pseudomonas aeruginosa during induction and carbon catabolite repression of histidase synthesis. AB - Inducibility of histidase (histidine ammonia-lyase, EC 4.3.1.3) in Pseudomonas putida and Pseudomonas aeruginosa was observed to be strongly affected by succinate-provoked catabolite repression, but this did not occur as a consequence of reduced intracellular cyclic adenosine 3',5'-monophosphate levels, and repression could not be alleviated by exogenously added cyclic adenosine 3,'5' monophosphate. Milder repression of histidase by lactate was also not reversed by the addition of cyclic adenosine 3',5'-monophosphate. These results, along with data showing intracellular cyclic adenosine 3',5'-monophosphate levels remained essentially constant during growth on such diverse carbon sources as histidine, acetamide, glucose, and succinate, indicated that catabolite repression of histidase synthesis by efficient carbon sources was not mediated through variations in internal cyclic adenosine 3,'5'-monophosphate. PMID- 6259130 TI - Homology between Escherichia coli plasmids ColE1 and p15A. AB - The location and extent of the homology between plasmids ColE1 and p15A were determined by analysis of heteroduplexes formed between them as well as with a related plasmid, pBR322, and by hybridization of radioactive deoxyribonucleic acids to restriction fragments of p15A and ColE1. The homology between the plasmids contained the entire region of ColE1 required for its replication as well as an additional 400 base pairs downstream from the origin of replication. This region on p15A, which was 980 +/- 43 base pairs, started at 0.1 of the molecular length from one end formed by cleavage with the restriction endonuclease BglI and extended to 0.54 of the molecular length from the same end. Restriction cleavage maps for the enzymes BglI, HpaI, HaeII, HaeIII, and HincII are also presented. PMID- 6259132 TI - Adenylate energy charge in Escherichia coli CR341T28 and properties of heat sensitive adenylate kinase. AB - Escherichia coli strain CR341T28 will not grow at temperatures above 34 degrees C in liquid medium, and the adenylate kinase of this strain is heat sensitive. When a culture was shifted from a permissive (30 degrees C) to a nonpermissive (36 degrees C) temperature, the adenylate energy charge fell from 0.9 to 0.2, with a concurrent decrease in the number of viable cells and in the specific activity of adenylate kinase. When cultures of the temperature-sensitive strain were grown at temperatures above 30 degrees C, the adenylate energy charge, the specific activity of adenylate kinase, and the growth rate were lower than the corresponding parameters for the parental strain. By isotopic labeling of the adenine nucleotides in vivo, it was determined that increasing growth temperatures between 30 and 34 degrees C for the heat-sensitive strain resulted in a decrease in the adenosine triphosphate-to-adenosine monophosphate and adenosine triphosphate-to-adenosine diphosphate ratios. Between 26 and 30 degrees C the adenosine triphosphate-to-adenosine diphosphate ratio was essentially normal in the temperature-sensitive strain, but the adenosine triphosphate-to adenosine diphosphate ratio was decreased. The adenylate ratios in the parental strain did not change between 30 and 34 degrees C. The adenylate kinase mass action ratio for each strain was essentially constant under all growth conditions. When assayed at 30 degrees C, the affinities of the enzyme from the mutant strain were somewhat lower than those of the parent adenylate kinase. The mutant enzyme also did not exhibit the substrate inhibition that was observed at high adenosine monophosphate concentrations with the parental enzyme. An increase in the assay temperature from 30 degrees to 40 degrees C had little or no effect on the Km values determined for the parental adenylate kinase, but caused the Km values determined for the mutant adenylate kinase to increase by a factor of two or more. PMID- 6259131 TI - Functional organization of plasmid pKM101. AB - Tn5 insertion mutants and in vitro-generated deletion mutants of the mutagenesis enhancing plasmid pKM101 have been used to identify several genetic regions on the pKM101 map. In clockwise order on the pKM101 map are: (i) the bla gene, coding for a beta-lactamase; (ii) the Slo region, responsible for retarding cell growth on minimal medium; (iii) the tra genes, enabling pKM101 to transfer conjugally; (iv) sensitivity to IKe phage (this function[s] maps within the tra region); (v) the muc gene(s), responsible for enhancing ultraviolet light and chemically induced mutagenesis in the cell; and (vi) the Rep region, essential for plasmid replication. The muc gene(s) and the Rep region are contained in a deoxyribonucleic acid region bounded by inverted repeated sequences. PMID- 6259133 TI - Intrastrand base pairing in single-stranded deoxyribonucleic acid from ColE1 derived plasmid pCR1. AB - Single strands of EcoRI-cleaved pCR1 deoxyribonucleic acid were examined by electron microscopy for intrastrand base pairing by using partial denaturing conditions. The locations of three stem and loop structures were mapped relative to the inverted repeat of Tn903. Potential roles and origins of these loops are discussed. PMID- 6259134 TI - Versatile cloning vector for Pseudomonas aeruginosa. AB - A pBR322:RSF1010 composite plasmid, constructed in vitro, was used as a cloning vector in Pseudomonas aeruginosa. This nonamplifiable plasmid, pMW79, has a molecular weight of 8.4 X 10(6) and exists as a multicopy plasmid in both P. aeruginosa and Escherichia coli. In P. aeruginosa strain PAO2003, pMW79 conferred resistance to carbenicillin and tetracycline. Characterization of pMW79 with restriction enzymes revealed that four enzymes (BamHI, SalI, HindIII, and HpaI) cleaved the plasmid at unique restriction sites. Cloning P. aeruginosa chromosomal deoxyribonucleic acid fragments into the BamHI or SalI site of pMW79 inactivated the tetracycline resistance gene. Thus, cells carrying recombinant plasmids could be identified by their carbenicillin resistance, tetracycline sensitivity phenotype. Deoxyribonucleic acid fragments of approximately 0.5 to 7.0 megadaltons were inserted into pMW79, and the recombinant plasmids were stably maintained in a recombination-deficient (recA) P. aeruginosa host. PMID- 6259135 TI - Regulation of dimorphism in Histoplasma capsulatum by cyclic adenosine 3',5' monophosphate. AB - During temperature-induced transition of the dimorphic pathogenic fungus Histoplasma capsulatum from the single yeast cell form to the multicellular mycelial form, there was an increase in intracellular cyclic adenosine 3',5' monophosphate (cAMP) levels as well as a striking accumulation of cAMP in the medium. cAMP levels also changed during the reverse mycelium-to-yeast transition. PMID- 6259136 TI - Temperature dependence of endocytosis mediated by the asialoglycoprotein receptor in isolated rat hepatocytes. Evidence for two potentially rate-limiting steps. AB - The rate of endocytosis of cell surface-bound [3H]-asialo-orosomucoid was determined as a function of temperature. Freshly isolated rat hepatocytes were allowed to bind [3H]asialo-orosomucoid at 4 degrees C, washed to remove nonbound ligand, and internalization was then assessed by the resistance of cell associated radioactivity to release by the Ca2+ chelator EDTA. At 10 degrees C or below, endocytosis is negligible. Above 10 degrees C, the rate of endocytosis is proportional to temperature but the increase of the rate of endocytosis with increasing temperature changes sharply at about 20 degrees C. From 10-20 degrees C, the apparent activation energy for endocytosis, calculated from an Arrhenius plot, is 45.9 kcal/mol and the temperature coefficient, Q10, is 15.6. However, between 20 and 41 degrees C, the calculated activation energy is 17.0 kcal/mol and the Q10 is 2.6. Although the rate of endocytosis of previously bound [3H]asialo-orosomucoid is very dependent on the temperature, the final extent of endocytosis is essentially temperature-independent between 14 and 37 degrees C. The results suggest that there are at least two steps in the overall process of endocytosis mediated by the asialoglycoprotein receptor on isolated hepatocytes which can be potentially rate-limiting, one at 10 degrees C and another at approximately 20 degrees C. PMID- 6259138 TI - Characterization of gonadotropin binding sites in the intracellular organelles of bovine corpora lutea and comparison with plasma membrane sites. AB - The specific binding of 125I-human choriogonadotropin (hCG) to plasma membranes, nuclear membranes, lysosomes, rough endoplasmic reticulum, heavy golgi, and medium and light golgi of bovine corpora lutea was dependent on the amount of protein, 125I-hCG concentration and incubation time. The bound hormone in all the organelles was able to rebind to fresh corresponding organelles. Scatchard analysis revealed a homogenous population of gonadotropin binding sites in plasma membrane, rough endoplasmic reticulum, heavy golgi, and medium and light golgi, whose binding affinities (Kd = 8.6-11.0 X 10(-11) M) were similar but whose number of available gonadotropin binding sites varied. Scatchard analyses of nuclear membranes and lysosome binding, on the other hand, were heterogenous (Nuclear membranes, 11 and 23 X 10(-11) M lysosomes, 3.4 and 130 X 10(-11) M). The rate constants for association (5.9 to 12.1 X 10(6) M-1 S-1) and dissociation (7.4 to 9.0 X 10(-4) S-1) were similar among different subcellular organelles except for nuclear membranes and lysosomes, where rate constants for association were significantly lower. The ligand binding specificity, lower effectiveness of human luteinizing hormone as compared to hCG in competition, the optimal pH, the lack of ionic requirements for binding, and the molecular size of 125I-hCG gonadotropin binding site complexes solubilized from various intracellular organelles were similar to those observed for plasma membranes. Numerous differences were also observed between intracellular organelles and plasma membranes as well as among intracellular organelles themselves with respect to binding losses due to exposure to low and high pH values, di- and monovalent cations, increasing preincubation temperatures, and a variety of enzymes and protein reagents. The possible reasons for these similarities as well as differences observed are discussed. The differences are viewed as an additional indication that contamination cannot solely explain the presence of gonadotropin binding sites in various intracellular organelles. PMID- 6259137 TI - Fluorescence anisotropy of a fatty acid covalently linked in vivo to the glycoprotein of vesicular stomatitis virus. AB - The covalently-attached fatty acid of the membrane glycoprotein (G) of vesicular stomatitis virus was fluorescently labeled biologically by isolating vesicular stomatitis virus from infected baby hamster kidney clone 21 cells that had been grown in the presence of 16(9-anthroyloxy)palmitate. The fluorescent labeling was specific for the G protein; the other viral membrane protein, the matrix (M) protein, was not labeled. Steady state fluorescence anisotropy of the 16(9 anthroyloxy)palmitate-labeled G protein reconstituted into dipalmitoylphosphatidylcholine vesicles indicated that the fatty acid attached to G protein is located in a dipalmitoylphosphatidylcholine domain that does not undergo the gel to liquid-crystalline phase transition. PMID- 6259139 TI - Deoxyribonuclease I in mammalian tissues. Specificity of inhibition by actin. AB - Enzymes of the DNase I class, similar to bovine pancreatic DNase I with respect to molecular weight and ionic and pH requirements, were found in various tissues of the rat. Their analysis was facilitated by a method for detection of nucleases in crude extracts after polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and subsequent renaturation of the enzymes. High levels of DNase I were found in digestive tissues, such as the parotid and submaxillary salivary glands and the lining of the small intestine., Appreciable levels were present in the lymph node, kidney, heart, prostate gland, and seminal vesicle. No activity was found in pancreatic extracts. However, under some conditions, tissues rich in proteases gave poor recovery of DNase I. Fourteen other tissues showed little or no DNase I. Inhibition of various DNase I enzymes by rabbit muscle actin was examined both in gels and in solution. Actin inhibited the bovine parotid DNase I as well as the bovine pancreatic enzyme, but actin did not inhibit any of the DNase I enzymes of the rat. This species specificity of actin inhibition makes it unlikely that the very strong association between monomeric actin and bovine DNase I is of general significance for cellular function. PMID- 6259140 TI - Stability of poliovirus RNA in cell-free translation systems utilizing two initiation sites. AB - The stability of purified poliovirus RNA in cell-free translation systems prepared from HeLa cells or rabbit reticulocytes has been examined. Degradation of the RNA occurs with a t1/2 of approximately 35 min at 30 degrees C under conditions used for in vitro translation. Degradation is due in part to activity in the cell lysate, and in part to contaminants in the commercial preparations of creatine phosphokinase used in the energy-regenerating system. Addition of crude preparations of initiation factors significantly slows degradation, presumably as a result of protein-RNA interactions which confer resistance to nuclease action. Prior treatment of RNA with methylmercury hydroxide has no effect on degradation rates. On the other hand, endogenous mRNA, present as a messenger ribonucleoprotein particle in extracts from poliovirus-infected HeLa cells, remains completely intact during in vitro translation. These infected cell extracts synthesize the normal complement of viral proteins and utilize two different initiation sites for translation. Treatment of the infected cell extract with micrococcal nuclease destroys the endogenous mRNA. Subsequent addition of exogenous RNA to the same extract results in the formation of a protein-associated RNA particle with sedimentation properties slightly different from the endogenous messenger ribonucleoprotein, and the added RNA is unstable. We conclude that two initiation sites can be utilized on intact poliovirus mRNA, and fragmentation of the RNA is not prerequisite for generation of a second site in this RNA. PMID- 6259141 TI - The interaction of H+ and K+ with the partial reactions of gastric (H+ + K+) ATPase. AB - The influence of H+ and K+ on the partial reactions and transport of gastric (H+ + K+)-ATPase was studied. Using transient kinetics, the effects and sidedness of effects of H+ and K+ on formation and breakdown of phosphoenzyme were determined in intact and lyophilized reconstituted vesicles in the absence and presence of gramicidin. Whereas increasing H+ concentrations on the ATP-binding face of the vesicles accelerates phosphorylation, increasing K+ concentrations inhibits phosphorylation. Increasing H+ on this side reduces K+ inhibition of the phosphorylation rate. At low ATP/K+ ratios, the phosphorylation step can become rate-limiting for steady state hydrolysis. Decreasing H+ accelerates dephosphorylation in the absence of K+. K+ on the internal or luminal face of the vesicles accelerates dephosphorylation, and this rate is reduced with increasing H+ concentrations. At low internal pH, K+-dependent dephosphorylation may become rate-limiting. H+ transport measurements using fluorescence quenching of acridine orange show that whereas internal K+ is required for H+ transport, external K+ inhibits the rate of formation of a pH gradient, and the inhibition is reduced by decreasing medium pH. The pH optimum for ATPase activity and transport correlated in the vesicles, and the K0.5 of K+ for transport correlated with data for intact parietal cells. PMID- 6259142 TI - High resolution experimental and theoretical thermal denaturation studies on small overlapping restriction fragments containing the Escherichia coli lactose genetic control region. AB - The distribution of thermal stability in the Escherichia coli lac control region is evaluated from the melting behavior of 5 short (80-219 base pairs (bp)) sequenced DNA restriction fragments containing various parts of this sequence. The thermal denaturation of these fragments was measured at 3 salt concentrations. The previous notion that the melting curves for small fragments are sharp and asymmetric in 0.01 M Na+ and broadened and less asymmetric at 0.105 and 0.505 M Na+ is confirmed and the possible explanations are discussed. The existence of two thermodynamic boundaries in this region is also confirmed. The exact location of the boundary upstream of the cyclic AMP receptor protein (CAP) binding site is accurately determined from melting experiments at 260 and 282 nm. The secondary boundary located between the promoter and operator sequence is apparent at the two higher salt concentrations and begins to disappear at the lower salt concentration. The physical interpretation of the melting experiments is compared to the results of theoretical predictions derived from the known sequence of the fragments. PMID- 6259143 TI - Protease mitogenic response of chick embryo fibroblasts and receptor binding/processing of human alpha-thrombin. AB - Quiescent cultures of chick embryo fibroblasts incubated with human alpha thrombin (14-219 pM) incorporated [methyl-3H]thymidine proportional to concentration. Inactivated forms of this protease (e.g. active-site-conjugated alpha-thrombin or its hirudin complex) had no mitogenic activity and did not compete with 124I-alpha-thrombin for binding to specific plasma membrane receptors. The noncoagulant but esterolytic active forms, gamma- and nitro-alpha thrombins, were weakly mitogenic and correspondingly competed weakly for binding. Trypsin competed equally as well as native thrombin for binding, whereas chymotrypsin, elastase, and human urokinase competed with 80-fold less affinity. Plasma, arginine-specific proteases associated with nerve or epidermal growth factors, insulin, and insulin-like growth factors did not compete for binding. These data demonstrate that (a) functional catalytic residues of the thrombin active site are necessary for mitogenic activity and for specific binding; (b) regions adjacent to the active site, i.e. the high affinity protein recognition site, appear to enhance binding; and (c) the receptor can discriminate between other proteases and binds those which are also mitogens for the avian cells. The characteristics of 125I-alpha-thrombin binding were determined, and it was found to be (i) proportional to cell number; (ii) optimal at pH 6.8; (iii) 70-90% specific; (iv) at equilibrium after 60 min of incubation at 22-24 degrees C or 180 min at 0-4 degrees C (the rate constants for association, i.e. ka, at 22 and 4 degrees C were 18 and 1.1 x 10(7) M-1 min-1, respectively); and (v) essentially nondissociable. Nondissociable thrombin that bound during incubation at 0-4 degrees C was distributed equally between trypsin-sensitive and insensitive compartments. Thrombin associated with the former was released into the media when the cells were incubated at 0-4 degrees C with hirudin or hydroxylamine, or transferred to the insensitive compartment when incubated at 22 degrees C. Finally, confluent cultures of fibroblasts bind 2-3 x 10(4) 125I-alpha-thrombin molecules/cell with an apparent binding constant, i.e. Kd, of 0.7 nM (a true Kd could not be determined because of the irreversible nature of thrombin binding). The binding capacity per cell and the apparent Kd value increased proportionally to an increase in culture density. PMID- 6259144 TI - Nucleotide sequence of the gene coding for the nitrogenase iron protein from Klebsiella pneumoniae. AB - We report the complete DNA sequence of the Klebsiella pneumoniae nifH gene, the gene which codes for component 2 (Fe protein or nitrogenase reductase) of the nitrogenase enzyme complex. The amino acid sequence of the K. pneumoniae nitrogenase Fe protein is deduced from the DNA sequence. The K. pneumoniae Fe protein contains 292 amino acids, has a Mr = 31,753, and contains 9 cysteine residues. We compare the amino acid sequence of the K. pneumoniae protein with available amino acid sequence data on nitrogenase Fe proteins from two other species, Clostridium pasteurianum and Azotobacter vinelandii. The C. pasteurianum Fe protein, for which the complete sequence is known, shows 67% homology with the K. pneumoniae Fe protein. Extensive regions of strong conservation (90-95%) are found, while other regions show relatively poor conservation (30-35%). It is suggested that these strongly conserved regions are of special importance to the function of this enzyme, and the findings are discussed in the light of evolutionary theories on the origin of nif genes. PMID- 6259145 TI - Hormonal regulation of hepatic glycogen synthase phosphatase. AB - Perfusion of livers from fed rats with medium containing glucagon (2 x 10(-10) or 1 x 10(-8) M) resulted in both time- and concentration-dependent inactivation of glycogen synthase phosphatase. Expected changes occurred in cAMP, cAMP-dependent protein kinase, glycogen synthase, and glycogen phosphorylase. The effect of glucagon on synthase phosphatase was partially reversed by simultaneous addition of insulin (4 x 10(-8) M), an effect paralleled by a decrease in cAMP. Addition of arginine vasopressin (10 milliunits/ml) resulted in a similar inactivation of synthase phosphatase and activation of phosphorylase, but independent of any changes in cAMP or its kinase. Phosphorylase phosphatase activity was unaffected by any of these hormones. Synthase phosphatase activity, measured as the ability of a crude homogenate to catalyze the conversion of purified rat liver synthase D to the I form, was no longer inhibited by glucagon or vasopressin when phosphorylase antiserum was added to the phosphatase assay mixture in sufficient quantity to inhibit 90-95% of the phosphorylase a activity. These data support the following conclusions: 1) hepatic glycogen synthase phosphatase activity is acutely modulated by hormones, 2) hepatic glycogen synthase phosphatase and phosphorylase phosphatase are regulated differently, 3) the hormone-mediated changes in synthase phosphatase cannot be explained by an alteration of the synthase D molecule affecting its behavior as a substrate, and 4) glycogen synthase phosphatase activity is at least partially controlled by the level of phosphorylase a. PMID- 6259146 TI - Extracellular regulation of fibroblast multiplication. Quantitative differences in nutrient and serum factor requirements for multiplication of normal and SV40 virus-transformed human lung cells. AB - The principles of Henri-Michaelis-Menten kinetic analysis were applied to directly relate the concentration of serum growth factors and individual nutrients in the culture medium to the multiplication rate of a population of normal (N-HLF) and SV40 virus-transformed (SV-HLF) human lung fibroblasts. When all nutrient concentrations were optimal and in steady state, the concentration of serum factors that was required to support a half-maximal rate of proliferation of both N-HLF and SV-HLF was similar. When the serum factor concentration was optimal and constant, SV-HLF cells exhibited a reduced requirement (p less than 0.001) for 12 of 27 individual nutrients that were examined. Serum factors control the cellular requirement for Ca2+, K+, Mg2+, phosphate ions, and 2-oxocarboxylic acids for multiplication of N-HLF (McKeehan, W. L., and McKeehan, K. A. (1980) Proc. Natl, Acad, Sci, U. S. A. 77, 3417-3421). SV-HLF exhibited a constitutively reduced requirement for Ca2+, K+, and Mg2+ which partially removed the requirement for the 3 ions for multiplication of SV HLF from the control of serum factors. The results suggest that SV40 virus transformation confers a growth advantage on human lung fibroblasts by alteration of their quantitative requirements for specific nutrients. PMID- 6259147 TI - Interaction of fluorescent gonadotropin-releasing hormone with receptors in cultured pituitary cells. AB - A fluorescent derivative of the gonadotropin-releasing hormone (GnRH) agonist analog, [D-Lys6]GnRH, was synthesized for receptor studies and shown to be biologically active. The rhodamine-derivatized peptide (Rh-GnRH) retained 40% of the receptor binding activity of [D-Lys6]GnRH, and 50% of the luteinizing hormone releasing activity assayed in cultured pituitary cells. The fluorescent analog was employed to visualize the distribution of GnRH receptors in cultured pituitary cells, using the technique of video-intensified fluorescence microscopy. The binding of Rh-GnRH was confined to the large gonadotrophs which comprised 15% of the cell population. The specificity of the binding was shown by the absence of significant fluorescence in the presence of a 100-fold excess of [D-Lys6]GnRH, or when Rh-GnRH was incubated with choriocarcinoma, neuroblastoma, or 3T3 cell lines devoid of GnRH receptors. The interaction of Rh-GnRH with living pituitary cells was characterized by an initial diffuse distribution, followed by the formation of polar aggregates that later appeared to be internalized. These observations emphasize the value of fluorescent derivatives of GnRH for elucidating the course of the interaction with specific receptors on pituitary gonadotrophs. The initial results indicate that GnRH-receptor complexes undergo aggregation during stimulation of luteinizing hormone release, and are later internalized for subsequent degradation and/ or intracellular actions. PMID- 6259148 TI - In vitro phosphorylation of the 36K protein in extract from Rous sarcoma virus transformed chicken fibroblasts. AB - When cell-free extracts of chickens embryo fibroblasts transformed by Rous sarcoma virus (RSV) were incubated with [gamma-32P]ATP, a protein having a Mr of 36,000 was phosphorylated. Two-dimensional electrophoresis of a mixture of phosphorylated proteins formed in vitro and in vivo showed that they are indistinguishable. The in vitro phosphorylation of the Mr = 36,000 protein was completely inhibited by serum isolated from rabbit bearing tumor formed by RSV. In addition, phosphorylation of the 36K protein does not occur if the extract was made from fibroblasts transformed by RSV tsNY68 and cultured at 42 degrees C or from fibroblasts infected with transformation defective RSV. The cell free phosphorylation of 36K protein was dependent on Mg2+ ions but not dependent on exogenously added cyclic AMP. PMID- 6259149 TI - Multiple alpha and beta tubulin genes represent unlinked and dispersed gene families. AB - Cloned cDNA sequences specific for alpha or beta tubulin mRNAs have been used to show that the multigene families which encode either alpha or beta tubulin are unlinked and dispersed throughout the chicken genome. Fractions of chicken chromosomes partially purified by centrifugation on a sucrose gradient were digested with restriction endonucleases and electrophoresed on agarose gels. The DNA was transferred to nitrocellulose filters and hybridized to labeled probes constructed from cloned cDNA sequences specific for alpha or beta tubulin. We find alpha tubulin sequences on four different chicken chromosomes and beta tubulin sequences on at least two different chromosomes. Moreover, using chicken chromosomes further purified with a fluorescent cell sorter, we have been able unambiguously to localize alpha tubulin genes to chromosome 1 and chromosome 8 and two of the beta genes to chromosome 2. PMID- 6259150 TI - In vitro synthesis of the F0 and F1 components of the proton translocating ATPase of Escherichia coli. AB - Specialized lambda transducing phage DNA containing the unc region of the Escherichia coli chromosome was used as template to direct an in vitro transcription/translation system. The results demonstrated synthesis of seven of the eight polypeptides of the proton translocating ATPase of this organism. The three polypeptides a, b, and c, constituting the F0 portion of the complex, were resolved by sodium dodecyl sulfatepolyacrylamide gel analysis and have apparent molecular weights (Mr = 24,000, 18,000, and 8,000-9,000) similar to the corresponding proteins produced in vivo. In addition, the alpha, beta, delta, and epsilon polypeptides of the F1 portion of the ATPase were also detected and their molecular weights correspond to the in vivo peptides. A 4.3-kilobase HindIII generated lambda unc DNA fragment was cloned onto plasmid vectors and was demonstrated to contain the genes for the three F0 and two of the F1 (alpha, delta) subunits. In addition, the polypeptides synthesized in vitro were precipitable with antibody prepared against purified F1. PMID- 6259151 TI - Regulation of actin in rat adrenocortical cells by corticotropin. AB - Corticotropin (ACTH) induces a characteristic retraction of rat adrenocortical cells in culture. Densitometric analysis of sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels of cell lysates showed that ACTH induced a 20% decrease in actin content. These results were fully confirmed by quantitation of actin by the DNase 1 inhibition assay. The decrease in actin is hormone-specific, concentration-dependent, and correlates temporally with the morphological change induced by ACTH. The change in actin content and the reorganization of microfilament ultrastructure may together mediate hormone regulation of cell shape at the cytoskeletal level. PMID- 6259152 TI - The relationship between calmodulin binding and phosphorylation of smooth muscle myosin kinase by the catalytic subunit of 3':5' cAMP-dependent protein kinase. AB - Smooth muscle myosin light chain kinase, a calmodulin-dependent enzyme, binds 1 mol of calmodulin/mol of kinase in the presence of calcium (Adelstein, R. S., and Klee, C. B. (1981) J. Biol. Chem. 256, in press. This enzyme is a substrate for cAMP-dependent protein kinase whether or not calmodulin is bound. When calmodulin is not bound to myosin kinase, protein kinase incorporates phosphate into two sites in myosin kinase. Under these circumstances, phosphorylation markedly lowers the rate of myosin kinase activity. The decrease in myosin kinase activity is due to a 10-20-fold increase in the amount of calmodulin necessary for 50% activation of kinase activity. The effect of phosphorylation on the activity of myosin kinase can be reversed by dephosphorylation using a purified phosphatase (Pato, M. D., and Adelstein, R. S. (1980) J. Biol. Chem. 255, 6535-6538) isolated from smooth muscle. When calmodulin is bound to myosin kinase, phosphate is incorporated into a single site with no effect on myosin kinase activity. The presence of at least two sites that can be phosphorylated in myosin kinase was confirmed by tryptic digestion of denatured myosin kinase. PMID- 6259153 TI - Dephosphorylation of rabbit skeletal muscle phosphorylase kinase. Evidence against the operation of the "second-site phosphorylation" mechanism of regulation. AB - The dephosphorylation of rabbit skeletal muscle phosphorylase kinase was studied using two purified rabbit skeletal muscle protein phosphatases. The first enzyme (Mr = 32,000) corresponds to the form we have previously termed protein phosphatase C. Phosphorylase kinase was found to be rapidly dephosphorylated by this enzyme. The site of dephosphorylation was examined, and it was shown that this enzyme was relatively specific for the dephosphorylation of the beta-subunit phosphate, as compared to the alpha-subunit phosphate, of phosphorylase kinase. Phosphate release from the beta-subunit was approximately 100-fold faster than from the alpha-subunit. More importantly, dephosphorylation of the beta-subunit phosphate was not significantly affected by phosphorylation of the alpha-subunit. The dephosphorylation of phosphorylase kinase by a second low molecular weight protein phosphatase, Mr = 33,500, was also studied. The specific activity of this enzyme toward phosphorylase kinase was only a fraction of that exhibited by the Mr = 32,000 phosphatase. This enzyme removed phosphate from both the alpha- and beta-subunits but more rapidly (about 4-fold) from the alpha-subunit. With neither of these enzyme preparations was there any evidence for the regulation of beta-subunit dephosphorylation by phosphorylation of the alpha-subunit as proposed by Cohen and Antoniw ((1973) FEBS Lett. 34, 43-47). PMID- 6259155 TI - Light-dependent inactivation of (Na+ + K+)-ATPase with a new photoaffinity reagent, chromium arylazido-beta-alanyl ATP. PMID- 6259154 TI - Regulation of brain cyclic nucleotide phosphodiesterase by calmodulin. A quantitative analysis. AB - Comparison of the parameters of Ca and Sr binding to bovine brain calmodulin with the activation of bovine brain phosphodiesterase by Ca2+ and Sr2+ at different calmodulin concentrations allows a quantitative description of the mechanism of activation of the enzyme. Equilibrium dialysis studies show that calmodulin possesses three high affinity (K'diss = 6 micoM) and one low affinity (K'diss = 200 microM) sites for Ca2+. All four sites display the same affinity for Sr2+ with K'diss = 180 microM. In the presence of calmodulin, soluble bovine brain phosphodiesterase is activated by Sr2+ to the same extent as by Ca2+. The activation of the enzyme shows the same Ca2+/Sr2+ selectivity ratio of 30 as the binding of the metal ions to calmodulin. Based on the findings that the Ca2+ or Sr2+ concentration at half-maximal activation of the enzyme depends on the concentration of calmodulin present, a quantitative analysis of activation was carried out as a function of the four calmodulin-metal complex species (CaM . Men). The data show that the activating species are CaM . Ca3, CaM . Ca4 or CaM . Sr3, CaM . Sr4. The interaction of these activating species with phosphodiesterase follows the Hill equation with a dissociation constant of 10( 9) M and a Hill coefficient of 2, irrespective of the binding characteristics of Ca2+ or Sr2+. The latter value agrees well with the fact that phosphodiesterase possesses two binding sites for calmodulin. PMID- 6259156 TI - The utilization of inactivation kinetics to demonstrate specificity of photoaffinity labeling. PMID- 6259157 TI - Receptor-mediated endocytosis of transferrin in developmentally totipotent mouse teratocarcinoma stem cells. PMID- 6259158 TI - Analogs of (2'-5')oligo(A). Endonuclease activation and inhibition of protein synthesis in intact cells. AB - Synthetic analogs of (2'-5')oligo(A) were assayed for endonuclease activation in cell extracts and for inhibition of protein synthesis in intact cells. The analogs are triadenylates: (i) methylated in the terminal 3'-OH; (ii) methylated at all three 3'-OH groups; (iii) with different numbers of phosphate groups at the 5' terminus or with a methylene group between the beta- and gamma-phosphate. Only 5'-phosphorylated monomethylated analogs activate an endonuclease in cell extracts and are powerful inhibitors of protein synthesis in intact cells. The analogs with only one 5'-terminal phosphate may require addition of another phosphate for activity since the kinase inhibitor 2-aminopurine prevents endonuclease activation by this compound but not by the di- and triphosphate terminated triadenylates. These results suggest that two terminal phosphates and one or two free 3'-OH are required for endonuclease activation and inhibition of protein synthesis. The monomethylated analogs are more active than (2'-5')pppA3 because of their resistance to degradation by cellular enzymes. Accordingly, the monomethylated analogs cause a prolonged inhibition of protein synthesis in human fibroblasts treated with nanomolar concentrations of these compounds. PMID- 6259159 TI - Use of formylated yeast initiator Met tRNA to define the NH2-terminal residues of rat preproinsulin and pregrowth hormone. AB - A method for unambiguously determining the initiator methionine residue and the adjacent NH2-terminal amino acid sequence of cell-free translation products of eukaryotic messenger RNA is described. In this procedure, the NH2 termini of nascent peptides are blocked by incorporating labeled formylmethionine instead of methionine, using yeast initiator tRNA in the wheat germ cell-free system. After immunoprecipitation of the desired product the radiolabeled material is treated with dansyl-Cl to irreversibly block all remaining free amino groups. The material is then deformylated by mild acid hydrolysis and subjected to automated Edman degradation. Only those products that had been synthesized with formylmethionine residues at their NH2-termini can then give rise to labeled phenylthiohydantoin derivatives during degradation. Using this method, we have defined the initiation sites in both rat preproinsulin and pregrowth hormone messenger RNAs. PMID- 6259160 TI - Evidence for high and low affinity alpha 2-receptors. Comparison of [3H]norepinephrine and [3H]phentolamine binding to human platelet membranes. PMID- 6259161 TI - The effect of histone hyperacetylation on the nuclease sensitivity and the solubility of chromatin. AB - We have examined the effects of histone hyperacetylation upon nuclease digestion of nuclei and subsequent fractionation of chromosomal material in the presence of MgCl2. DNase I shows a maximum sensitivity towards hyperacetylated nuclei at somewhat elevated ionic strengths (150-200 mM NaCl), whereas micrococcal nuclease exhibits no specificity for acetylated nuclei over a broad range of ionic strengths. Fractionation in the presence of MgCl2 of hyperacetylated nuclei digested with micrococcal nuclease results in a substantial increase in the amount of soluble chromatin relative to that obtained with control nuclei. This increased yield of Mg2+-soluble chromatin results from the recruitment into this fraction of oligonucleosomes containing extremely hyperacetylated histones. These results suggest that contiguous nucleosomes containing highly acetylated histones may be altered in their ability to interact with themselves and with other nucleosomes. PMID- 6259162 TI - Receptor-mediated catabolism of homologous low density lipoproteins in cultured pig hepatocytes. PMID- 6259163 TI - Variations in the structure of radiolabeled glycopeptides from the glycoprotein of vesicular stomatitis virus grown in four mouse teratocarcinoma cell lines. PMID- 6259164 TI - Vitamin B6 metabolism in Morris hepatomas. AB - The enzymes involved in the metabolism of vitamin B6 were measured in Morris hepatomas and livers of female Buffalo rats fed pyridoxine-sufficient and deficient diets. Pyridoxal phosphate levels in plasmas hepatomas, and livers were also determined. Nontumor-bearing animals were maintained as controls. Regardless of the B6 nutritional status, the concentration of pyridoxal phosphate was lower in the hepatomas than in the livers of the host animals. The apoenzyme levels of ornithine decarboxylase, a pyridoxal phosphate-dependent enzyme, were higher in the hepatomas from animals fed the B6-deficient diet. Liver pyridoxine kinase activity was higher in B6-sufficient animals. In contrast, tumor pyridoxine kinase activity was influenced by B6 intake and was significantly lower than that in host liver. Liver pyridoxine phosphate oxidase activity was not significantly affected by B6 intake or by the presence of tumor. In contrast, hepatomas had little or no pyridoxine phosphate oxidase activity. Pyridoxine phosphate phosphatase activity was elevated in tumors relative to livers. These data indicate that the metabolism of vitamin B6 is markedly different in the hepatomas than in host or control livers and suggest that the tumor is apparently incapable of the complete synthesis of co-enzymatically active pyridoxal phosphate from inactive precursor forms such as pyridoxine. PMID- 6259165 TI - Purification and characterization of an apurinic/apyrimidinic endonuclease from HeLa cells. AB - An endodeoxyribonuclease from HeLa cells acting on apurinic/apyrimidinic (AP) sites has been purified to apparent homogeneity as judged by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. The presence of Triton X-100 was necessary throughout the purification for stabilization and stimulation of activity. The endonuclease has an apparent native molecular weight of 32,000 determined by molecular sieving and an apparent subunit molecular weight of 41,000 as judged by its electrophoretic mobility in SDS-polyacrylamide gels. The activity has an absolute requirement for Mg2+ or Mn2+ and a broad pH optimum between 6.7 and 9.0 with maximal activity near pH 7.5. The enzyme has no detectable exonuclease activity, nor any endonuclease activity on untreated duplex or single-stranded DNA. It is inhibited by adenine, hypoxanthine, adenosine, AMP, ADP-ribose, and NAD+, but it is unaffected by caffeine, the pyrimidine bases, ADP, ATP, or NADH. The use of a variety of damaged DNA substrates provided no indication that the enzyme acts on other than AP sites. The enzyme appears to cleave AP DNA so as to leave deoxyribose-5-phosphate at the 5' terminus and a 3'-OH at the 3' terminus; it also removes deoxyribose-5 phosphate from AP DNA which has deoxyribose at the 3' terminus. Specific antibody has been produced in rabbits which interacts only with a 41,000-dalton protein present in the purified enzyme (presumably the enzyme itself), as well as with partially purified AP endonuclease fractions from human placenta and fibroblasts. PMID- 6259167 TI - Polyamines stimulate DNA-directed DNA synthesis catalyzed by mammalian type C retroviral DNA polymerases. AB - In the presence of optimal concentrations of Mg2+, rates of activated (gapped) DNA-directed DNA synthesis by purified mammalian type C retroviral DNA polymerases are stimulated greater than 10-fold by the polyamines spermine and spermidine. Such stimulation was not observed using either similar concentrations of the polyamines cadaverine or putrescine or exogenously provided salt or ammonium ions. Avian type C as well as mammalian type B and type D retroviral DNA polymerases, in contrast to the mammalian type C enzyme, were found to be relatively insensitive to spermine and spermidine stimulation. Kinetic analysis of the polyamine stimulation of activated DNA-directed DNA synthesis carried out using spermine and purified Rauscher leukemia virus DNA polymerase revealed at least two distinct mechanisms of activation of DNA synthesis. 1) At DNA concentrations below 2.5 micrograms/ml, spermine appears to interact with the enzyme-DNA complex in order to stimulate synthesis. 2) At DNA concentrations above 2.5 micrograms/ml, increased spermine stimulation is observed which appears to be due to its direct interaction with the activated DNA template resulting in either selective limitation of the formation of "dead-end" enzyme-DNA complexes or its ability to convert such nonproductive enzyme binding sites into productive sites for the initiation of synthetic activity. The addition of spermine to reaction mixtures was found to increase both the apparent Km and Vmax of the activated (gapped) DNA-directed reaction with regard to template concentration. PMID- 6259166 TI - Characterization of (8-lysine) vasopressin binding sites on a pig kidney cell line (LLC-PK1). Evidence for hormone-induced receptor transition. PMID- 6259168 TI - Mode of enzyme-bound poly(ADP-ribose) synthesis and histone modification by reconstituted poly(ADP-ribose) polymerase-DNA-cellulose complex. PMID- 6259169 TI - Superoxide production by an unusual aldehyde oxidase in guinea pig granulocytes. Characterization and cytochemical localization. AB - An aldehyde oxidase extracted from guinea pig granulocytes with isotonic KCl catalyzes the oxidation of a variety of aliphatic aldehydes and 2-OH-pyrimidine. The stoichiometry of the oxidation of 2-OH-pyrimidine is consistent with the reaction 2-OH-pyrimidine + OH- + O2 leads to uracil + H2O2. Between 75 and 90% of the peroxide produced results from dismutation of superoxide formed as an intermediate. The Km for 2-OH-pyrimidine is approximately 1.65 mM and the maximum velocity is 22.9 +/- 5.5 S.D. nmol of superoxide/min/10(7) cells. This same maximum velocity is observed for the substrates isobutyraldehyde, propionaldehyde, and acetaldehyde. Unlike other aldehyde oxidases, this enzyme is inactive with purines as substrates and is insensitive to antimycin A, menadione, and Triton X-100. The enzyme is inhibited by cyanide, methanol, and arsenite. The apparent molecular weight is approximately 340,000 +/- 25,000 and the pH optimum is in the range of 7.5 to 9.0. Electron cytochemistry reveals an association of this oxidase with the phagosome membrane. The potential significance of this oxidase is discussed in relation to microbicidal mechanisms. PMID- 6259170 TI - A specific substrate from rabbit cerebellum for guanosine 3':5'-monophosphate dependent protein kinase. I. Purification and characterization. AB - A protein that exhibits greater substrate specificity for cGMP-dependent protein kinase than for cAMP-dependent protein kinase has been purified 8,000-fold from cytosol of rabbit cerebellum to apparent homogeneity as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The protein, termed G-substrate, is a monomer of 23,000 daltons. It is heterogeneous on isoelectric focusing, exhibiting three isoelectric forms over the pH range of 5.2-5.6 cGMP-dependent protein kinase catalyzes the incorporation of 2 mol of phosphate/mol of G substrate, both into threonine residues. The protein has a high content of aspartate, glutamate, and proline. The hydrodynamic properties, heat stability, and acid solubility of this protein are consistent with an unfolded, nonglobular structure. G-substrate is localized primarily in the cytosol of cerebellum, although low concentrations of a phosphorylated protein with a similar molecular weight are detected in other brain regions. PMID- 6259171 TI - A specific substrate from rabbit cerebellum for guanosine 3':5'-monophosphate dependent protein kinase. II. Kinetic studies on its phosphorylation by guanosine 3':5'-monophosphate-dependent and adenosine 3':5'-monophosphate-dependent protein kinases. AB - Kinetic studies on the activity of purified cGMP-dependent protein kinase and catalytic subunit of cAMP-dependent protein kinase have been carried out using a protein termed G-substrate (see preceding paper) as the phosphate acceptor. Each enzyme catalyzed the phosphorylation of 2.0-2.1 mol of 32P/mol of G-substrate, with phosphorylation occurring primarily at threonine residues. When phosphorylation was carried out in the simultaneous presence of the two enzymes, the stoichiometry increased only slightly, to a value of 2.4, suggesting that both enzymes phosphorylated the same two sites. Initial rate studies on the phosphorylation of G-substrate by cGMP-dependent protein kinase yielded a Km of 0.21 microM and a Vmax of 2.2 mumol/min/mg. Similar studies with the cAMP dependent protein kinase yielded a Km of 5.8 microM and a Vmax of 2.3 mumol/min/mg. cGMP-dependent protein kinase thus exhibited a high degree of specificity towards this substrate which was apparently based on selective substrate binding rather than catalytic efficacy. The activity of cGMP-dependent protein kinase towards G-substrate was maximal at pH 7.5-8.0 and a Mg2+ concentration of 1-3 mM. Activity declined sharply at high ionic strength (greater than 20 mM KCl). PMID- 6259172 TI - A specific substrate from rabbit cerebellum for guanosine-3':5'-monophosphate dependent protein kinase. III. Amino acid sequences at the two phosphorylation sites. AB - G-substrate is a protein present in cerebellum which is a major endogenous substrate for cyclic GMP-dependent protein kinase, and one of the few known proteins phosphorylated more effectively by cyclic GMP-dependent protein kinase than by cyclic AMP-dependent protein kinase. G-substrate has been shown to be phosphorylated on two threonine residues, and the amino acid sequences surrounding these sites, which correspond to about 30% of the primary structure, are: Leu-Asn-Val-Glu-Ser-Asp-Gln-Lys-Lys-Pro-Arg-Arg-Lys-Asp-Thr(P)-Pro-Ala-Leu His- Ile-Pro-Pro-Phe-Ile-Ser-Gly-Val-Ile-Ser-Gln-Asn SITE 1 Leu-His-Asn-Thr-Asp Leu-Glu-Gln-Gln-Lys-Pro-Arg-Arg-Lys-Asp-Thr(P)-Pro-Ala-Leu- His-Thr-Ser-Pro-Phe Gln-Ser-Gly-Val-Arg SITE 2 The amino acid sequences surrounding the phosphorylated residues show 18 identities over a sequence of 26 residues, and suggest that G-substrate contains an internal gene duplication. Site-1 appears to be located 17 residues from the COOH terminus of the protein. Site 1 and site 2 are phosphorylated at similar rates by cyclic GMP-dependent protein kinase. In contrast, cyclic AMP-dependent protein kinase phosphorylates site 1 4-fold more rapidly than site 2. A decapeptide sequence surrounding the phosphothreonine residues in G-substrate shows 5 identities with that surrounding the phosphothreonine residue in protein phosphatase inhibitor 1. Inhibitor 1, a specific substrate for cyclic AMP-dependent protein kinase, also resembles G substrate in its physical properties. The possible function of G-substrate and the molecular specificities of cyclic AMP-dependent protein kinase and cyclic GMP dependent protein kinase are discussed in the light of these results. PMID- 6259173 TI - Activation of the Sendai virus fusion protein (f) involves a conformational change with exposure of a new hydrophobic region. AB - The F protein of paramyxoviruses is actively involved in the induction of membrane fusion. This fusion may be between viral and cellular membranes, as in the initiation of infection or in virus-induced lysis of erythrocytes, or between the plasma membranes of different cells. The F protein is activated by proteolytic cleavage to yield two disulfide-linked polypeptides (F1 and F2); however, its mechanism of action is not clear. In the present study, the conformations of the inactive, uncleaved precursor of glycoprotein (F0), and the active, cleaved form (F1,2) have been compared. The UV circular dichroism spectra of the two forms of the F protein indicate that cleavage results in a conformational change. Detergent-binding studies by velocity sedimentation analysis of Triton X-100-protein complexes revealed an increase in exposed hydrophobic surface of the protein on cleavage. The inactive F0 bound an estimated 27 molecules of Triton X-100/F polypeptide; these molecules are presumably bound to the hydrophobic region of the glycoprotein that anchors the spike-like protein in the virus membrane and that is common to both forms of F. The active form, F1,2, bound 67 molecules of Triton X-100. This increase in the number of detergent binding sites upon F protein activation indicates the presence of a hydrophobic region that is peculiar to the active form, and that may be of functional significance in the membrane fusion reaction. PMID- 6259175 TI - Malignant lesions masquerading as popliteal cysts. A report of three cases. PMID- 6259174 TI - Characterization of a novel calmodulin from Dictyostelium discoideum. AB - We have purified calmodulin from the eukaryotic microorganism Dictyostelium discoideum (Clarke, M., Bazari, W. L., and Kayman, S. C. (1980) J. Bacteriol. 141, 397-400) and have compared it to calmodulin purified from bovine brain. The two proteins behaved almost identically during fractionation on ion exchange and gel filtration columns and on isoelectric focusing gels. Dictyostelium calmodulin had one-third the specific activity of brain calmodulin in the Ca2+-dependent activation of brain cyclic nucleotide phosphodiesterase; this activation was inhibited for both proteins by 25 microM trifluoperazine. Dictyostelium calmodulin also activated erythrocyte (Ca2+ + Mg2+)-ATPase and interacted with the inhibitory subunit of skeletal muscle troponin. Competition radioimmune assays showed that Dictyostelium calmodulin could compete with brain calmodulin for antibodies to brain calmodulin. These similarities indicate a close relationship between Dictyostelium and brain calmodulin and suggest that the functional capabilities of the protein have been conserved even among evolutionarily distant species. However, substantial differences in primary structure were detected by amino acid analyses and peptide mapping. Most interesting is the lack of trimethyllysine in Dictyostelium calmodulin. This unusual amino acid, which is commonly found in calmodulins, is therefore not essential for interaction between calmodulin and the calmodulin-regulated proteins tested here. PMID- 6259176 TI - Structural evidence that botulinum toxin blocks neuromuscular transmission by impairing the calcium influx that normally accompanies nerve depolarization. AB - Taking advantage of the fact that nerve terminal mitochondria swell and sequester calcium during repetitive nerve stimulation, we here confirm that this change is caused by calcium influx into the nerve and use this fact to show that botulinum toxin abolishes such calcium influx. The optimal paradigm for producing the mitochondrial changes in normal nerves worked out to be 5 min of stimulation at 25 Hz in frog Ringer's solution containing five time more calcium than normal. Applying this same stimulation paradigm to botulinum-intoxicated nerves produced no mitochondrial changes at all. Only when intoxicated nerves were stimulated in 4-aminopyridine (which grossly exaggerates calcium currents in normal nerves) or when they were soaked in black widow spider venom (which is a nerve-specific calcium ionophore) could nerve mitochondria be induced to swell and accumulate calcium. These results indicate that nerve mitochondria are not damaged directly by the toxin and point instead to a primary inhibition of the normal depolarization-evoked calcium currents that accompany nerve activity. Because these currents normally provide the calcium that triggers transmitter secretion from the nerve, this demonstration of their inhibition helps to explain how botulinum toxin paralyzes. PMID- 6259177 TI - Nerve growth factor-induced alteration in the response of PC12 pheochromocytoma cells to epidermal growth factor. AB - PC12 cells, which differentiate morphologically and biochemically into sympathetic neruonlike cells in response to nerve growth fact, also respond to epidermal growth factor. The response to epidermal growth factor is similar in certain respects to the response to nerve growth fact. Both peptides produce rapid increases in cellular adhesion and 2-deoxyglucose uptake and both induce ornithine decarboxylase. But nerve growth factor causes a decreased cell proliferation and a marked hypertrophy of the cells. In contrast, epidermal growth factor enhances cell proliferation and does not cause hypertrophy. Nerve growth factor induces the formation of neuritis; epidermal growth factor does not. When both factors are presented simultaneously, the cells form neurites. Furthermore, the biological response to epidermal growth fact, as exemplified by the induction of ornithine decarboxylase, is attenuated by prior treatment of the cells with nerve growth factor. PC12 cells have epidermal growth factor receptors. The binding of epidermal growth factor to these receptors is rapid and specific, and exhibits an equilibrium constant of 1.9 x 10(-9) M. Approximately 80,000 receptors are present per cell, and this number is independent of cell density. Treatment of the cells with nerve growth factor reduces the amount of epidermal growth factor binding by at least 80 percent. The decrease in receptor binding begins after approximately 12-18 h of nerve growth factor treatment and is complete within 3 d. Scratchard plots indicate that the number of binding sites decreases, not the affinity of the binding sites for epidermal growth factor. PMID- 6259178 TI - Differentiation of a teratocarcinoma line: preferential development of cholinergic neurons. AB - A line of embryonal carcinoma cells, PCC7-S, established in vitro from a spontaneous testicular teratocarcinoma, has been studied. Upon removing the cells from a low density monolayer culture system and permitting the cells to form aggregates in suspension, we observed a change of several physical and biochemical parameters: (a) reduction in average cell volume, (b) blockage and accumulation of cells in G1, (c) rise in secreted protease activity, (d) rise in acetylcholinesterase and choline acetyltransferase activities, and (e) disappearance of embryonic antigen F9. Although PCC7 aggregates did not undergo substantial morphological changes while suspended, when aggregates 4 or more days old were allowed to attach to plastic tissue culture dishes, substantial neurite outgrowth occurred over the next 1-3 d. This process was markedly enhanced by the addition to the growth medium of carboxymethylcellulose and inhibitors of DNA synthesis. Transmission electron microscopy disclosed a neurite ultrastructure consistent with that of neuronal processes. A veratridine-stimulated, tetrodotoxin-blocked sodium influx of 100 nmol/min per mg protein was also observed in these differentiated surface cultures. This cell line is discussed in terms of its utility for the study of early events leading to a commitment to cellular differentiation, as well as for the investigation of terminal differentiation to cholinergic neurons. PMID- 6259179 TI - Effect of oxygen tension on human peripheral blood leukocytes: lysosomal enzyme release and metabolic responses during phagocytosis. AB - We found that nonlethal lysosomal enzyme release from human peripheral blood leukocytes during phagocytosis of opsonized zymosan in vitro was modified by the oxygen tension under which the cells were incubated; with decreasing Po(2), zymosan-induced release of lysosomal enzymes was potentiated. The effect on enzyme release could not be attributed secondarily to an effect on phagocytosis, because, as others have reported, Po(2) had little effect on that response. Metabolic responses that accompany phagocytosis were also modified by oxygen tension. Stimulation of oxidation by way of the pentose cycle was further enhanced by increasing Po(2). Conversely, anaerobic glycolysis was promoted by decreasing oxygen tension. ATP levels fell as a function of time and concentration of phagocytic stimulus, mirroring lysosomal enzyme release as modified by Po(2). Cyclic AMP levels fell during phagocytosis and lysosomal enzyme release, a change that could act to facilitate lysosomal enzyme release. However, the fall in nucleotide level was greatest with highest Po(2) (i.e., when lysosomal enzyme release was least). The inverse relationship between oxidative metabolism and enzyme release suggested that a product of oxidative metabolism might adversely influence enzyme release. Sulfhydryl antioxidants (Cysteine, glutathione) and scavengers of oxygen-derived reactants (superoxide dismutase, catalase, benzoate, hypoxanthine, xanthine, histidine, azide) all potentiated zymosan- stimulated enzyme release. These findings are consistent with the interpretation that one or more factors (e.g., superoxide anion, hydrogen peroxide, hydroxyl radical, singlet oxygen), generated in association with the burst of oxidative metabolism which accompanies phagocytosis, acts to inhibit lysosomal enzyme release. PMID- 6259180 TI - Rapid rounding of human epidermoid carcinoma cells A-431 induced by epidermal growth factor. AB - Epidermal growth factor (EGF) induces rapid rounding of A-431 human epidermoid carcinoma cells in Ca(++)-free medium. Cell rounding is not induced by a variety of other polypeptide hormones, antiserum to cell membranes, local anesthetics, colchicine, cytochalasin B, or cyclic nucleotides. However, trypsin, like EGF, induces rounding of A- 431 cells in the absence of Ca(++). Both trypsin- and EGF induced rounding are temperature dependent, appear to be energy dependent, and are inhibited by cytochalasins, suggesting that the active participation of microfilaments in cell rounding. However, a medium transfer experiment suggests that EGF-induced rounding is not attributable to secretion of a protease, and a number of serine protease inhibitors have no effect on the EGF-induced rounding process. Cell rounding is not attributable to the slight stimulation by EGF of the release of Ca(++) that is observed in the Ca(++)-free medium, as stimulation of such release by the ionophore A23187 neither induces cell rounding nor blocks EGF-induced rounding. Cells that have rounded up after treatment with EGF or trypsin spread out upon addition of Ca(++) to the medium, even in the continuing presence of EGF or typsin. Like the cell-rounding process, the cell-spreading process is temperature dependent, appears to be energy dependent, and is inhibited by cytochalasin B. Thus, EGF does not destroy the ability of the cell to spread; rather, in the presence of the EGF (or trypsin), cell spreading and the maintenance of the flattened state become dependent on external Ca(++). Because untreated cells remain flattened in the absence of Ca(++), the data suggest that EGF may disrupt Ca(++)-independent mechanisms of adhesion normally present in A-431 cells. PMID- 6259182 TI - Transmembrane potential changes during phagocytosis in rat alveolar macrophages. AB - Studies were carried out to measure changes in the transmembrane potential of rat alveolar macrophages during exposure of the cells to zymosan particles or to the membrane perturbant, phorbol-12-myristate-13-acetate (PMA), and to determine if changes in membrane potential are related to superoxide anion release. Exposure of the cells to either zymosan or PMA leads to membrane depolarization, which precedes superoxide anion release. Furthermore, the magnitude of the depolarization is dependent upon the concentration of either zymosan or PMA. During exposure of the alveolar macrophages to increasing levels of zymosan, there is an increase in the amount of superoxide released as well as an increase in the magnitude of the depolarization. Incubation of the cells in medium containing 150 mM K+, a medium which causes membrane depolarization, leads to superoxide release from resting cells and a decrease in the amount of superoxide released from cells exposed to zymosan. These results indicate that release of superoxide anion from rat alveolar macrophages is related to membrane depolarization and suggest that the transmembrane potential change may act as a signal to initiate the phagocytotic responses of the cells. PMID- 6259181 TI - Inefficient internalization of receptor-bound low density lipoprotein in human carcinoma A-431 cells. AB - Human epithelioid carcinoma A-431 cells are known to express unusually large numbers of receptors for the polypeptide hormone epidermal growth factor. The current studies demonstrate that this cell line also expresses 5- to 10-fold more low density lipoprotein (LDL) receptors per cell than either human fibroblasts or Chinese hamster ovary (CHO) cells. As visualized with an LDL-ferritin conjugate, the LDL receptors in A-431 cells appeared in clusters that were distributed uniformly over the cell surface, occurring over flat regions of the membrane as well as over the abundant surface extensions. Only 4% of the LDL receptors were located in coated pits. The LDL receptors in A-431 cells showed the same affinity and specificity as the LDL receptors in human fibroblasts and other cell types. In addition, they were subject to feedback regulation by sterols in the same manner as the LDL receptors in other cells. However, in contrast to other cell types in which the receptor-bound LDL is internalized with high efficiency, in the A-431 cells only a small fraction of the receptor-bound LDL entered the cell. In CHO cells approximately 66% of the LDL receptors were located over coated regions of membrane, and the efficiency of LDL internalization was correspondingly 10-fold higher than in A-431 cells. These findings support the concept that the rate of LDL internalization is proportional to the number of LDL receptors in coated pits and that the inefficiency of internalization in the A 431 cells is caused by a limitation in the ability of these cells to incorporate their LDL receptors into coated pits. PMID- 6259184 TI - Stimulation of autophosphorylation of liver cell membrane proteins by calcium and partial hepatectomy. AB - Partial hepatectomy in the rat stimulated the phosphorylation of three proteins (Mr 100,000, 48,000, and 35,000) in the plasma membranes of the proliferatively activated cells of the liver remnant. The autophosphorylation of these plasma membrane proteins began to rise about 8 hours after surgery, peaked at 14 hours, and then returned to the original low level by 24 hours. This increase in autophosphorylation was not evident in isolated plasma membranes from other proliferatively activated liver cells, such as those in fetal liver or hepatomas. The protein kinase responsible for the phosphorylation of the three membrane proteins was activated by calcium but appeared both cyclic-AMP- and calmodulin independent. PMID- 6259183 TI - External cell surface protein phosphorylation in normal and Rous sarcoma virus transformed chick embryo fibroblasts. AB - Normal and Rous sarcoma virus (RSV)-transformed chick embryo fibroblasts growing on plastic dishes were incubated with ATP (gamma 32P) in situ to detect external cell surface protein kinase activity. Under the conditions employed, 32P was incorporated exclusively into proteins, specifically those at the external cell surface, as radioactivity was removed by trypsin treatment of labeled whole cells. In addition, exogenous histones were phosphorylated when added to the reaction mixture. Cyclic nucleotides had virtually no effect on 32P incorporation, suggesting that little or no cyclic nucleotide-dependent protein kinase activity was present at the external cell surface. Cell surface protein kinase activity was higher in transformed than in normal cells, and, using a temperature-sensitive RSV src mutant, this difference was shown to be transformation-specific. Several differences were observed in the cell surface proteins phosphorylated in normal and transformed cells and at least two of these were transformation-specific. These data suggest that changes in external cell surface protein phosphorylation are associated with RSV transformation and thus could play a role in the formation of the transformed cell phenotype. PMID- 6259185 TI - Passive membrane permeability to small molecules and ions in transformed mammalian cells: probable role of surface phosphorylation. AB - Addition of ATP to medium surrounding intact, transformed 3T3 cells causes the formation of aqueous channels in the plasma membrane. This effect of extracellular ATP is sharply dependent on the pH and temperature of the incubation medium, and is inhibited by low levels of La3+ or ruthenium red; inhibition is also obtained with concentrations of Mg2+ ions that exceed a ratio of Mg/ATP of one. The effect of ATP on membrane channel formation is unaffected by chelators of metal ions or by prior modification of the cell surface with various surface-active enzymes or sulfhydryl reagents. Under conditions which favor aqueous channel formation, incubation of intact 3T6 cells with ATP (gamma 32P) leads to phosphorylation of two membrane components with apparent molecular weight of 40,000 (40K) and 110,000 (110K) daltons; the 110K component which is unaffected by trypsin under normal conditions is rendered trypsin-sensitive by the phosphorylation reaction, probably as a result of a conformational change. Conditions which inhibit aqueous channel formation also inhibit phosphorylation of the 110K protein and decrease the labeling of the 40K component. These results indicate the probable role of cell surface phosphorylation, involving one or both of these components, in the formation of aqueous channels in transformed 3T3 cells. Aqueous channel formation by extracellular ATP is not associated with gross unfolding of the cell surface as revealed by lactoperoxidase-catalyzed iodination of the 3T6 cell surface. PMID- 6259186 TI - Transmembrane potential changes associated with superoxide release from human granulocytes. AB - Treatment of human granulocytes with concanavalin A, phorbol myristate acetate (PMA), N-formyl-methionyl-leucyl-phenylalanine (FMLP), and A23187 (a calcium ionophore) stimulates the release of superoxide anion and the generation of chemiluminescence. The fluorescent probe, Di-S-C3(5), has been used to monitor shifts in membrane potential in response to these stimulants which precede the secretion of superoxide. Concanavalin A, PMA, and FMLP induce a biphasic shift in transmembrane potential (Em), i.e., a rapid depolarization followed by a prolonged hyperpolarization. This depolarization is dependent on both external sodium and calcium while the hyperpolarization is inhibited by ouabain which blocks the electrogenic Na-K pump. In contrast, A23187 induces a rapid and prolonged depolarization. This monophasic shift in Em is dependent on external calcium. These results suggest that depolarization acts as a signal to initiate events associated with the "respiratory burst" of these phagocytes. PMID- 6259187 TI - Na+, K+-ATPase in HeLa cells after prolonged growth in low K+ or ouabain. AB - Effects of long-term, subtotal inhibition of Na+-K+ transport, either by growth of cells in sublethal concentrations of ouabain or in low-K+ medium, are described for HeLa cells. After prolonged growth in 2 X 10(-8) M ouabain, the total number of ouabain molecules bound per cell increases by as much as a factor of three, mostly due to internalization of the drug. There is only about a 20% increase in ouabain-binding sites on the plasma membrane, representing a modest induction of Na+, K+-ATPase. In contrast, after long-term growth in low K+ there can be a twofold or greater increase in ouabain binding per cell, and in this case the additional sites are located in the plasma membrane. The increase is reversible. To assess the corresponding transport changes, we have separately estimated the contributions of increased intracellular [Na+] and of transport capacity (number of transport sites) to transport regulation. During both induction and reversal, short-term regulation is achieved primarily by changes in [Na+]i. More slowly, long-term regulation is achieved by changes in the number of functional transporters in the plasma membrane as assessed by ouabain binding Vmax for transport, and specific phosphorylation. Parallel exposure of cryptic Na+,K+-ATPase activity with sodium dodecyl sulfate in the plasma membranes of both induced and control cells showed that the induction cannot be accounted for by an exposure of preexisting Na+,K+-ATPase in the plasma membrane. Analysis of the kinetics of reversal indicates that it may be due to a post-translational event. PMID- 6259188 TI - [Intrathoracic chemodectomas. A report on four observations (author's transl)]. AB - Intrathoracic chemodectomas are extremely rare tumours, the number, published up to the present time being less than 50. We wish to report here four personal cases, all resected. The diagnosis was never made before surgery but solely by histopathology. The course was benign in two cases and malignant with slow progression in one case and malignant with rapid progression in the other. On the basis of these four cases, a general review is undertaken of this particular site on the basis of publications in the literature. PMID- 6259189 TI - Effects of "jet lag" on hormonal patterns. I. Procedures, variations in total plasma proteins, and disruption of adrenocorticotropin-cortisol periodicity. PMID- 6259190 TI - Stimulation of adenosine 3',5'-monophosphate and sex steroids in the spermatic venous blood after human chorionic gonadotropin injection into human testes. AB - To study the participation of cAMP in the action of gonadotropin on testicular steroidogenesis in the human testis in vivo, we have measured the concentrations of cAMP, testosterone, 5 alpha-dihydrotestosterone, estrone, 17 beta-estradiol, and hCG in the spermatic venous blood of the patients with prostatic cancer after hCG injections into the testis. Five minutes after hCG administration, spermatic cAMP increased to 5 times the pretreated level, and after 30 min, it increased to 20 times the pretreated level. Testosterone increased gradually after hCG injection, and the 2-fold increase was demonstrated at 50 min. Although the pattern of the changes in spermatic 5 alpha-dihydrotestosterone was similar to that of testosterone, a statistically significant increase was not observed after hCG administration. Estrogen production was also stimulated by hCG. These results are consistent with the view that cAMP may participate in the action of hCG upon steroidogenesis in the testis of human beings in vivo, as has previously been observed with rat and human testes in vitro. PMID- 6259191 TI - Characterization of vasoactive intestinal peptide receptors in human colonic epithelial cells. AB - Receptors, i.e. specific binding sites for vasoactive intestinal peptide (VIP), have been characterized in human colonic epithelial cells isolated by EDTA treatment using 125I-labeled porcine VIP. The binding was time and temperature dependent. Conditions of apparent equilibrium were obtained at 15 C after 45 min of incubation in the presence of 2.1-7.4 micrograms cell DNA-ml; these conditions minimized the degradation of the peptide and the binding sites. Native VIP competitively inhibited the binding of [125I]VIP in the range of 3 x 10(-11)-10( 7) M, and half-maximal inhibition was observed at 2 x 10(-9) M VIP. Scatchard analysis of these data was consistent with the existence of two classes of binding sites: 7.8 x 10(-9) high affinity sites/microgram DNA with a dissociation constant (Kd) of 1.4 x 10(-9) M, and 12.0 x 10(10) low affinity sites/microgram DNA with a Kd of 46 x 10(-9) M. Among the natural hormones structurally related to VIP, gastric inhibitory polypeptide (GIP) and glucagon had no effect on the binding of labeled porcine VIP. Porcine secretin inhibited [125I]VIP binding, but at doses 1000 times higher than those of porcine VIP. Studies of the coupling between the binding of VIP and the stimulation of cAMP formation indicated a nonlinear relationship between the two processes, with full activation of the cAMP-producing system with occupancy of only a limited number of the binding sites. The presence of binding sites with high affinity for VIP coupled with the cAMP production in human colonic epithelial cells support the concept that this peptide may contribute to the physiological regulation of the functions of the human colonic epithelium in normal and pathological conditions. PMID- 6259192 TI - Maximal urine-concentrating ability: familial hypocalciuric hypercalcemia versus typical primary hyperparathyroidism. AB - Impairment of urine-concentrating ability is common in persons with chronic hypercalcemia. We assessed urine-concentrating ability in 40 patients with typical primary hyperparathyroidism and 10 patients with familial hypocalciuric hypercalcemia, a disorder resembling typical primary hyperparathyroidism but lacking some of its clinical complications. Urine-concentrating ability was determined during a dehydration test of 18-22 h. The two patient groups were comparable with respect to serum calcium concentration and creatinine clearance. In the group with familial hypocalciuric hypercalcemia, the duration of hypercalcemia was probably greater, because it commences during infancy; the urinary excretion rate for calcium was lower [6.6 +/- 5.4 (mean +/- 1 SD) vs. 14.8 +/- 7.5 meq/day; P less than 0.005]. Patients with familial hypocalciuric hypercalcemia showed higher maximal urinary osmolality (800 +/- 150 vs. 664 +/- 130 mosmol/kg; P less than 0.0005). Among the patients with typical primary hyperparathyroidism, there was a negative association between maximal urinary osmolality and urinary cAMP (r = -0.40; P less than 0.05), but there was no significant relation between maximal urinary osmolality and the urinary excretion rate for calcium. Among 18 patients retested within 1 month after surgical correction of typical primary hyperparathyroidism, urine-concentrating ability did not improve. In patients with typical primary hyperparathyroidism, impairment in urine-concentrating ability reflects features of the chronic disease state, as it is not rapidly reversible by correction of that state. However, in patients with familial hypocalciuric hypercalcemia, longstanding hypercalcemia is not associated with obvious impairment of urine-concentrating ability. Complete or partial freedom from impairment of urine-concentrating ability and from calcareous renal disease are expressions of the generally mild course in familial hypocalciuric hypercalcemia. PMID- 6259193 TI - Radioimmunoassay of plasma equilin and estrone in postmenopausal women after the administration of premarin. AB - A RIA for the measurement of plasma equilin (3-hydroxy-1,3,5-(10)7-estratetraen 17-one) and estrone in postmenopausal women and other estrogen-deficient women on exogenous equine estrogen replacement therapy is described. Antiserum against estriol-3,16,17-trihemisuccinate-HSA and high specific activity [2,4-3H]equilin and [6,7-3H]estrone were used in the assay procedure. Specificity of the assay was achieved by separation of equilin from estrone by chromatography on micro Celite partition columns using silver nitrate as the stationary phase. The sensitivity of the standard curves for both equilin and estrone was 10-20 pg, and the smallest amount of estrone and equilin that could be measured accurately in the plasma was 250 pg/ml for both steroids. The coefficient of variation for both steroids ranged from 1-8%, over a range of 250-5000 pg/ml plasma. The interassay coefficients of variation for equilin and estrone were 4.6% and 2.4%, respectively. After the administration of 10 mg Premarin iv, maximum concentrations of 4 and 11.2 ng/ml for equilin and estrone, respectively, were obtained after 20 min. Thereafter, both steroids disappeared from the plasma gradually. When 10 mg Premarin were administered orally, equilin and estrone appeared in the blood gradually, and maximum levels of 560 and 1400 pg/ml were reached after 3 and 5 h for equilin and estrone, respectively. Equilin gradually disappeared, and by 24 h, only small amounts (125 pg/ml) were detectable. The levels of estrone declined more rapidly, though it was still detectable after 24 h. These preliminary results indicate that equilin sulfate is converted to circulating unconjugated equilin in a manner similar to the conversion of circulating estrone sulfate to estrone. PMID- 6259194 TI - In vivo modulation of somatomedin receptor sites: effects of growth hormone treatment of hypopituitary children. AB - We have previously demonstrated that somatomedin (SM) can induce the loss of specific SMC receptors on cultured IM-9 lymphocytes in a time- and concentration dependent manner. To investigate the acute regulation of SM binding under in vivo conditions, we have evaluated SM receptors on circulating mononuclear cells obtained from 12 hypopituitary dwarfs before and after 4 days of human GH administration (0.1 U/kg . day). Plasma SM levels, measured by radioreceptor assay, rose from 0.37 +/- 0.08 U/ml (mean +/- SEM) to 1.00 +/- 0.10 (P less than 0.001). Concomitantly, specific binding of [125I]SMC to 50 x 10(6) mononuclear cells/ml fell from 13.61 +/- 0.97% to 10.40 +/- 0.85% (P less than 0.02). The decrease in specific binding was predominantly secondary to a reduced number of SMC receptor sites per cell, with no alteration in receptor affinity. Overall, a significant inverse correlation was observed between plasma SM levels and mononuclear cellular binding of [125I]SMC (P less than 0.001). The data demonstrate that treatment of hypopituitary dwarfs with conventional therapeutic doses of human GH results in significant acute increases in plasma SM levels in the majority of subjects, with a reciprocal decline in the specific binding of [125I]SMC. We conclude that SM, like insulin, is capable of regulating homologous receptor concentrations under both in vitro and in vivo conditions. PMID- 6259195 TI - Urinary and nephrogenous adenosine 3',5'-monophosphate in the hypercalcemia of malignancy. PMID- 6259196 TI - Lack of effect of calcium infusion on blood glucose and plasma insulin levels in patients with insulinoma. AB - In vitro calcium plays a fundamental role in regulating insulin secretion. On the other hand, the influence of calcium excess on insulin release in vivo is not clearly defined. Recently, calcium infusion has been proposed as a provocative test for the diagnosis of insulin-secreting tumors. A 2-h infusion of calcium gluconate was performed (4 mg/kg . h) in six patients with islet cell adenoma. As a result, mean calcium plasma levels increased from 9.6 +/- 0.4 to 11.6 +/- 0.8 mg/100 ml. During calcium infusion, blood glucose and plasma insulin concentrations remained unchanged. These observations suggest that calcium fails to stimulate basal insulin secretion even in cases of organic hyperinsulinism. They show that calcium infusion is not helpful as a provocative test in the diagnosis of insulinoma. PMID- 6259197 TI - Receptors for multiplication-stimulating activity on human arterial and venous endothelial cells. AB - Primary cultures of endothelial cells were prepared from the arteries and veins of human umbilical cords. Both arterial and venous endothelial cells demonstrated specific receptors for the insulin-like growth factor MSA (Multiplication Stimulating Activity). Insulin, at concentrations up to 10(-7) M, had little effect on 125I-MSA binding whereas MSA was congruent to 1% as potent as insulin in competing with 125I-insulin binding. Serum containing anti-insulin receptor antibodies blocked binding of 125I-insulin to the endothelial cells but had little effect on 125I-MSA binding. We conclude that human endothelial cells have specific and distinct receptors for both MSA and insulin. PMID- 6259198 TI - Detection of respiratory syncytial, parainfluenza type 2, and adenovirus antigens by radioimmunoassay and enzyme immunoassay on nasopharyngeal specimens from children with acute respiratory disease. AB - Four-layer antispecies radioimmunoassay (RIA) and enzyme immunoassay (EIA) procedures were developed for the detection of respiratory syncytial virus (RSV), parainfluenza type 2 virus, and adenovirus antigens in nasopharyngeal specimens from children hospitalized for acute respiratory disease. Polystyrene beads (RIA) or flat-bottomed polystyrene microtiter plates (EIA) were used as the solid phases, guinea pig anti-virus immunoglobulins were used as the captive antibodies, rabbit anti-virus immunoglobulins were used as the secondary antibodies, and 125I-labeled sheep anti-rabbit (RIA) or horseradish peroxidase labeled swine anti-rabbit (EIA) immunoglobulins were used as the indicator antibodies. A comparison of the EIAs and RIAs with routinely used immunofluorescence (IF) techniques was made with 164 nasopharyngeal specimens collected from children with acute respiratory disease. Only 3 of 66 RSV IF positive specimens were negative in RSV RIA, and of 83 RSV, parainfluenza type 2 virus, and adenovirus IF-negative specimens, 1 was positive in RSV RIA. Of 4 parainfluenza type 2 virus IF-positive and 11 adenovirus IF-positive specimens, each was positive in corresponding RIAs, and all 83 IF-negative specimens were negative in parainfluenza type 2 virus and adenovirus RIAs. The results of the RSV, parainfluenza type 2, and adenovirus EIAs confirmed the results of corresponding RIAs in each selected case tested. The RIAs and EIAs were found to be as specific and sensitive as IF techniques, and more practical in the rapid detection of respiratory viruses in nasopharyngeal secretions. PMID- 6259199 TI - Hydrolytic enzymes of Moraxella bovis. AB - Certain strains of Moraxella bovis produce tissue-damaging enzymes which may initiate or potentiate infectious bovine keratoconjunctivitis. Thirteen reference strains of this species were characterized physiologically and screened for production of various enzymes by some conventional biochemical tests and the API ZYM system (Analytab Products, Plainview, N.Y.). All 13 strains were hemolytic. All hydrolyzed Tween 80 and Tween 85 and displayed C4 esterase, C8 esterase lipase, and C14 lipase activities. All produced phosphoamidase and phosphatase. All were able to hydrolyze casein and gelatin. All produced leucine and valine aminopeptidases and fibrinolysin. Twelve produced hyaluronidase or were agarolytic. Three hydrolyzed chondroitin sulfate. Nine strains autoagglutinated. Five produced catalase, and two produced cystine aminopeptidase. PMID- 6259200 TI - Molecular epidemiology of human rotaviruses in Melbourne, Australia, from 1973 to 1979, as determined by electrophoresis of genome ribonucleic acid. AB - Rotaviruses contain a double-stranded ribonucleic acid genome consisting of 11 segments. Gel electrophoresis separates genome segments and allows identification of strain differences. This electrophoretic typing technique was applied to rotavirus specimens from 116 children and 72 newborn babies. Between 1973 and 1979, 17 different electropherotypes of rotavirus were observed in children with acute gastroenteritis. These electropherotypes showed a sequential pattern of appearance, with a limited number of electropherotypes present at any given time. By contrast, only two electropherotypes were identified from isolates from newborn babies in seven hospitals during 1975 to 1979. These two electropherotypes were very similar and were never identified in children with acute gastroenteritis. One of the neonatal electropherotypes was found in the nurseries of five different hospitals and persisted in one hospital for 4 years. Electrophoretic typing techniques can be applied routinely and reproducibly to small samples of feces and could prove to be of value in epidemiological studies of rotavirus infection PMID- 6259202 TI - Assessment of laboratory improvement by the Center for Disease Control Diagnostic Immunology Proficiency Testing Program. AB - The data accumulated from 1969 to 1979 in the Diagnostic Immunology portion of the Center for Disease Control Proficiency Testing Program were evaluated for evidence of change in performance among the participating laboratories. Evidence of improved performance was found for the rubella, rheumatoid factor, tularemia, quantitative immunoglobulin (immunoglobulin G, A, and M), and hepatitis B tests. No evidence of change was detected for the streptococcal enzyme, C-reactive protein, infectious mononucleosis, antinuclear antibodies, Salmonella and Brucella agglutinins, and syphilis tests. Data obtained from other tests were inadequate to determine trends. In most tests, deficiencies were identified which could be corrected and thereby could improve performance. It is pointed out that proficiency testing not only improves laboratory performance, but also can be used to evaluate performance levels, identify method, standard, or performance deficiencies, educate, estimate impact of possible changes, serve as external quality control, and document changes. PMID- 6259201 TI - Enzyme-linked immunosorbent assay for detection of pertussis immunoglobulin A in nasopharyngeal secretions as an indicator of recent infection. AB - An enzyme-linked immunosorbent assay was developed for detection of immunoglobulin A (IgA) antibody to Bordetella pertussis (PsIgA) in nasopharyngeal secretions as an indicator of recent infection. Secretion specimens submitted for pertussis culture were examined for PsIgA by this technique. Of 348 specimens tested, B. pertussis was cultured from 57, and PsIgA was detected in 8 culture positive and 40 culture-negative specimens. The average time between onset of symptoms and specimen collection for the culture-positive, PsIgA-negative specimens was 10 days; for the culture-positive, PsIgA-positive specimens, 15 days; and for the culture-negative, PsIgA-positive specimens, 36 days. Examination of paired samples available from several culture-proven cases demonstrated conversion from a negative PsIgA in the early sample to a positive PsIgA in the follow-up sample. Our results indicate that PsIgA is produced during natural human infection and does not arise as a result of parenteral vaccination. PsIgA usually appears in the nasopharyngeal secretions during the second or third week of illness and persists for at least 3 months. The detection of PsIgA in secretions may be a valuable diagnostic aid in culture-negative patients with pertussis. PMID- 6259203 TI - Human infective dose determinations for oral poliovirus type 1 vaccine in infants. AB - The 50, 10, and 1% human infective doses of poliovirus type 1 vaccine administered orally to 32 infants were estimated to be 72, 39, and 20 tissue culture infective doses, respectively. PMID- 6259204 TI - Antigenically intermediate human adenovirus strain associated with conjunctivitis. AB - Two strains of an antigenically intermediate human adenovirus were isolated from eye specimens from cases of conjunctivitis. The viruses were doubly neutralized by antisera to adenoviruses 15 and 29 but possessed the hemagglutinins of adenovirus 8 or 9. PMID- 6259205 TI - Pituitary gonadotropin-releasing hormone receptors. Effects of castration, steroid replacement, and the role of gonadotropin-releasing hormone in modulating receptors in the rat. AB - To study the role of gonadotropin-releasing hormone (GnRH) receptors in the regulation of gonadotropin secretion, we used D-125I-alanine6 des glycyl10 GnRH ethylamide (D-125I-Ala analog), a nondegradable, superagonist GnRH analog to assess GnRH receptors on rat pituitary membranes. Receptor affinity in intact adult rats was 5.0 X 10(9) M-1 and was unchanged after castration in both sexes. Castration of adult male and female rats produced a twofold increase in GnRH binding capacity by 7 d and binding capacity remained elevated for the subsequent 14 d. GnRH receptor number rose more rapidly after castration in males than females, and the time-course of receptor rise was similar to the increase in serum gonadotropin levels. The increase in GnRH binding capacity was prevented by gonadal steroid replacement at the time of castration in both sexes. Injections of the GnRH analog, D-Ser6 (TBu) des Gly10 GnRH ethylamide for 4 d produced a 70% increase in GnRH receptor number in intact male rats and testosterone-replaced castrates. The same regimen, however, failed to increase the elevated receptor numbers present after castration. Administration of rabbit anti-GnRH serum concomitant with castration inhibited the rise in both GnRH receptor number and luteinizing hormone. The changes in pituitary GnRH receptors parallel previously demonstrated changes in hypothalamic secretion of GnRH. Thus, GnRH probably regulates its own receptor in vivo and gonadal steroids may influence pituitary GnRH receptors by changing hypothalamic GnRH secretion. PMID- 6259207 TI - Seroepidemiological study of relationships between Epstein-Barr virus and rheumatoid arthritis. AB - To elucidate the relationship between Epstein-Barr virus (EBV) and rheumatoid arthritis (RA), we measured antibodies to RA-associated nuclear antigen (anti RANA) and three other EBV-related antigens in the sera of RA patients and controls. Our study groups consisted of 89 patients with definite or classical RA, mean age 56, male/female ratio 47:42; and 53 normal and osteoarthritis controls, mean age 51, male/female ratio 25:28. In addition to anti-RANA, we measured antibodies to viral capsid antigen (anti-VCA), early antigen (anti-EA) and EBV-associated nuclear antigen (anti-EBNA). Anti-RANA was detected in 71% of RA patients but in only 6% of controls. Elevated anti-VCA titers (greater than 1:160) were more common in RA patients than controls, 31% compared with 15%. The geometric mean titer of anti-VCA was significantly higher iun the RA group, 133 compared with 58. Anti-EA was present in 53% of RA patients but only 19% of controls. Anti-EA in elevated titers (greater than 1:20) was present in 26% of RA patients but only 7% of controls. Characterization of the anti-EA antibodies revealed that the RA patients reacted primarily with the diffuse component, whereas the majority of the controls reacted with the restricted component of the EA complex. In contrast, the frequencies, distributions, and geometric mean titers of anti-EBNA were not significantly different between the two groups. Correlative analysis of these antibodies showed highly significant relationships between anti-VCA and anti-EA, and anti-RANA and anti-EBNA in the RA group. These data are compatible with the interpretation that RA patients have either more active EBV infections than controls or an altered regulation of their immune response to this infectious agent. PMID- 6259206 TI - Effects of trifluoperazine on function and structure of toad urinary bladder. Role of calmodulin vasopressin-stimulation of water permeability. AB - Calcium ion plays a major regulatory role in many hormone-stimulated systems. To determine the site of calcium's action in the toad urinary bladder, we examined the effect of trifluoperazine, a compound that binds specifically to the calcium binding protein, calmodulin, and thereby prevents activation of enzymes by the calcium- calmodulin complex. 10 microM trifluoperazine inhibited vasopressin stimulation of water flow, but did not alter vasopressin's effects on urea permeability or short-circuit current. Trifluoperazine also blocked stimulation of water flow by cyclic AMP and methylisobutylxanthine, implying a "postcyclic AMP" site of action. Consistent with these results, trifluoperazine did not decrease epithelial cyclic AMP content or the cyclic AMP-dependent protein kinase activity ratio. Assay of bladder epithelial supernate demonstrated calmodulin like activity of 1.5 U/microgram protein. Morphologic studies of vasopressin treated bladders revealed that trifluoperazine did not alter the volume density of cytoplasmic microtubules or significantly decrease the number of fusions between cytoplasmic, aggregate-containing, elongated vesicles and the luminal membrane. Nonetheless, the frequency of luminal membrane aggregates, structures that correlate well with luminal membrane water permeability, was decreased by greater than 50%. Thus, trifluoperazine appears to inhibit the movement of intramembranous particle aggregates from the fused intracellular membranes to the luminal membrane, perhaps by blocking an effect of calcium on microfilament function. PMID- 6259208 TI - Respiratory burst enzyme in human neutrophils. Evidence for multiple mechanisms of activation. AB - Alteration of the surface of human neutrophils with the nonpenetrating, protein inactivating agent p-diazobenzenesulfonic acid (DASA) was found to prevent activation of the respiratory burst by some stimuli, but not others. Production of superoxide anion (O2-) stimulated by concanavalin A or the chemotactic peptide formyl-methionyl-leucyl-phenylalanine FMLP was inhibited by DASA pretreatment, whereas O2- production stimulated by phorbol myristate acetate (PMA), sodium fluoride. or the ionophore A23187 was not inhibited by DASA. Pretreatment with DASA inhibited oxygen uptake stimulated by FMLP, but not oxygen uptake stimulated by PMA. DASA reproducibly inhibited activities of two known surface enzymes Mg++ ATPase and alkaline phosphatase, by 45-55% and 60-70%, respectively. The inhibition by DASA of O2- production did not appear to be caused by interference with binding of the affected stimuli, since pretreatment with DASA did not inhibit release of the lysosomal enzymes lysozyme and myeloperoxidase induced by concanavalin A or FMLP. Membrane-rich particulate fractions from neutrophils have been shown to contain NADPH-dependent oxidative activity that is presumably responsible for the phagocytosis-associated respiratory burst of intact cells. The PMA-activated enzyme was susceptible to inhibition of directly exposed to DASA in this particulate fraction. These findings suggest that more than one mechanism exists for activation of the respiratory burst oxidase in human neutrophils, and that the neutrophil possesses at least one oxidase that is not an ectoenzyme. PMID- 6259209 TI - Importance of the vasoactive intestinal peptide receptor in the stimulation of cyclic adenosine 3',5'-monophosphate in gallbladder epithelial cells of man. Comparison with the guinea pig. AB - An EDTA procedure was used to prepare isolated epithelial cells of human gallbladder devoid of endogenous vasoactive intestinal peptide (VIP) as measured by radioimmunoassay. Specific binding sites for VIP were characterized in these cells. At 37 degrees C, the binding of (125)I-labeled VIP reached a peak within 20 min and then declined rapidly. At 15 degrees C, binding was stable between 90 and 180 min of incubation. Binding of the labeled peptide was inhibited by concentrations of native VIP of 30 pM-0.1 muM. Half-maximal inhibition was observed at 2 nM. Scatchard analysis indicated two functionally independent classes of receptor sites: 62,000 high affinity sites/cell with a dissociation constant (K(d)) of 1.3 nM, and 510,000 low affinity sites/cell with a K(d) of 16.2 nM. Secretin inhibited tracer binding but with a 1,000 times lower potency than native VIP. VIP strongly stimulated adenosine 3':5' monophosphate (cyclic AMP) production in human gallbladder epithelial cells. At 37 degrees C, 0.1 nM and 10 nM VIP raised cyclic AMP levels 44 and 100 times above the basal level, respectively. Maximal values remained constant between 60 and 90 min at 15 degrees C. The importance of the VIP-induced cyclic AMP rise was related, at least in part, to a low phosphodiesterase activity in human gallbladder epithelial cells. At equilibrium, during a 60-min incubation at 15 degrees C, cyclic AMP production was noted at concentrations of VIP as low as 3 pM. Maximal and half-maximal stimulations were observed at 10 nM and 0.2 nM VIP, respectively. Secretin also stimulated cyclic AMP production but with a 10,000 lower potency than VIP. In the guinea pig, VIP and secretin were equipotent stimulators of cyclic AMP in gallbladder epithelial cells. This particular feature was shown to be due to receptors specific for each peptide that were present in these cells. PMID- 6259210 TI - Healing of rickets with phosphate supplementation in the hypophosphatemic male mouse. AB - The hypophosphatemic male mouse, an animal model for human vitamin D-resistant rickets, is characterized by low serum phosphorus concentration due to increased urinary phosphate excretion, rickets, osteomalacia, and dwarfism. Because phosphate administration can heal rickets but not osteomalacia in the human disease, we have compared the effect of phosphate supplementation on the epiphyseal and endosteal bone mineralization in the mutant animal. Phosphate was given in drinking water for 137 d and the biochemical and bone responses were assessed by analytical and histomorphometric methods. Treatment with phosphate normalized the endochondral calcification (vertebral growthplate thickness: 83 +/ 5 SD vs. controls [+/Y] 73 +/- 8 micrometers, NS), but did not correct the endosteal bone mineralization (mineralization front: 13.6 +/- 2.7 vs. +/Y 67.1 +/ 6.9% osteoid surface, P less than 0.001, endosteal mean osteoid seam thickness: 46.4 +/- 6.1 vs. +/Y 3.3 +/- 0.3 micrometers, P less than 0.001). In addition, both osteoblastic and osteoclastic recruitment and activity were stimulated, as a result of a probable increase in parathyroid hormone secretion following the phosphate induced fall in serum calcium. Our results show that in the hypophosphatemic mouse, phosphate supplementation can heal the epiphyseal, but not the endosteal defective bone mineralization. Then, the biochemical and skeletal response to phosphate therapy appear to be similar to what we have observed in the human disease, further stressing the interest of the animal model. PMID- 6259211 TI - Elevated levels of antibodies to Epstein-Barr virus antigens in sera and synovial fluids of patients with rheumatoid arthritis. AB - The frequencies and levels of antibodies to Epstein-Barr virus (EBV)-specific antigens were determined in paired sera and synovial fluids from patients with rheumatoid arthritis (RA) and in sera from patients with other connective tissue diseases; i.e., systemic lupus erythematosus, progressive systemic sclerosis, and osteoarthritis (OA). The specimens were also tested for the presence of antibodies to RA-associated nuclear antigen. Compared to healthy controls, the patients' sera showed increased frequencies of elevated antibody titers (>/=320) to Epstein-Barr viral capsid antigen, a correspondingly enhanced (twofold to threefold) geometric mean titer, and an increased frequency of antibodies at elevated titers (>/=10), usually to the restricted component and rarely the diffuse component of the early antigen complex. Levels of antibody to the EBV associated nuclear antigen were within the normal range. Enhancement of antibody titers was more pronounced in seropositive RA patients (i.e., positive for rheumatoid factor) than in those who were not. Enhancement was also found in systemic lupus erythematosus and progressive systemic sclerosis. Antibody to RA associated nuclear antigen was detected at an increased frequency only in the group of seropositive RA patients (90%), as compared to 8-15% in the other connective tissue diseases and 6-8% in healthy controls. The antibody titers in the synovial fluids equaled or were at most twofold higher or lower than those in the sera. In addition, levels of EBV-specific antibodies were studied serially over a period of 6-10 mo in patients with RA and OA. Parameters of disease activity were determined and compared to antibody levels. EBV-specific antibodies in sera of OA patients remained constant and within normal limits throughout the study. Although EBV-specific antibodies were often elevated in RA patients, they also remained constant, with the exception of three patients, who showed gradual increases in one of the four antibodies, which did not correlate with disease activity. PMID- 6259212 TI - Human lung angiotensin converting enzyme. Purification and antibody preparation. AB - To enable its immunohistologic localization, angiotensin converting enzyme (EC 3.4.15.1) from human lung was solubilized by trypsinization and purified approximately 2,660-fold to apparent homogeneity from a washed lung particulate fraction. The specific activity of pure enzyme was estimated to be 117 mumol/min per mg protein with the substrate hippuryl-l-histidyl-l-leucine. Consistent with previously described lung enzyme studies, catalytic activity was strongly inhibited by EDTA, O-phenanthroline, SQ 20,881, and SQ 14,225 and increased by CoCl(2). SQ 20,881 was a somewhat more potent inhibitor than SQ 14,225, unlike rabbit lung enzyme. The Michaelis constant (K(m)) with hippuryl-l-histidyl-l leucine was 1.6 mM. The molecular weight was estimated at 150,000 from sucrose density gradient centrifugation. Sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed a single polypeptide chain estimated at 130,000 daltons. Rabbit antibody to human lung enzyme was prepared by parenteral administration of pure angiotensin-converting enzyme in Freund's adjuvant. Rabbit antibody to human lung angiotensin-converting enzyme appeared to crossreact weakly with the rabbit enzyme and strongly inhibited the catalytic activity of the enzymes from human serum, lung, and lymph node. The specificity of the rabbit antibody and purity of the final human lung enzyme preparation was suggested by the single precipitin lines obtained by radial double immunodiffusion, and by the coincidence of enzyme catalytic activity and immunoreactivity on polyacrylamide gel electrophoresis, with both relatively pure and highly impure enzymes. Generally applicable sensitive analysis of acrylamide gels for immunoreactivity (and subsequently for any other activity) by use of intact gel slices in radial double immunodiffusion was devised. Human lung enzyme was very tightly bound to and catalytically active on anti-human enzyme antibody covalently bound to Sepharose 4B, and could not be readily dissociated without inactivation. Antibody to human lung angiotensin converting enzyme has permitted tissue localization of the enzyme, which appears to be clinically useful in diseases associated with abnormal abundance of angiotensin-converting enzyme in tissues, such as sarcoidosis. PMID- 6259213 TI - Mechanism of adrenal angiotensin II receptor changes after nephrectomy in rats. AB - At 48 h after bilateral nephrectomy in rats there is a two- to threefold increase in the number of adrenal angiotensin II receptors and a decrease in Kd of smooth muscle angiotensin II receptors. These changes have been attributed to the absence of circulating angiotensin II. Serum K+, which increases after nephrectomy may be an important and overlooked modulator. Therefore, the present experiments were designed to assess the role of K+ as a regulator of angiotensin II receptors after nephrectomy. Serum K+ was controlled with Na polystyrene sulfonate (Kayexalate), a resin designed to exchange Na+ for K+ in the gastrointestinal tract. Acutely nephrectomized rats were divided into two groups: experimental animals received Kayexalate resin every 12 h for four doses, and controls received Kayexalate exchanged with KCl in vitro before gavage. There was a significant positive correlation serum K+ and aldosterone (r = 0.78, P less than 0.001). Kayexalate maintained a normal serum K+ of 5.9 +/- 0.2 meq/liter (n = 27), aldosterone 25 +/- 3 ng/dl (n = 27) and adrenal receptor concentration of 934 +/- 156 fmol/mg protein (n = 4). Control animals had significantly higher serum K+ of 10.5 +/- 0.4 meq/liter (n = 23), aldosterone 435 +/- 32 (n = 23), and adrenal receptors of 2726 +/- 235 fmol/mg protein (n = 4). There was a linear relationship between serum K+ and number of adrenal receptors (r = 0.87). No such relationship was present in uterine smooth muscle. Therefore, these studies demonstrate that K+ modulates the number of adrenal but not smooth muscle angiotensin II receptors after nephrectomy. This is the first evidence that potassium modulates angiotensin II receptors independently of changes in angiotensin II blood levels. PMID- 6259214 TI - Effect of parathyroid hormone on rat heart cells. AB - Myocardiopathy is common in uremia, but its cause in unknown. Excessive entry of calcium in heart cells by catecholamines has been shown to cause necrosis of myocardium. The high blood levels of parathyroid hormone (PTH) in uremia may also enhance entry of calcium into heart cells and exert deleterious effects on the heart. We examined the effect of PTH on rat heart cells grown in culture. Both amino-terminal (1-34) PTH and intact (1-84) PTH, but not the carboxy-terminal (53 84) PTH produced immediate and sustained significant rise in beats per minute and the cells died earlier than control. The effect was reversed if PTH was removed from medium, and was abolished by inactivation of the hormone. There was a dose response relationship between both moieties of PTH and the rise in heart beats, but the effect of 1-84 PTH was significantly greater than that of 1-34 moiety. PTH stimulated cyclic AMP production within 1 min, and cyclic AMP remained significantly elevated thereafter. The effect of PTH required calcium, was mimicked by calcium ionophore, was prevented by verapamil and was not abolished by alpha- or beta-adrenergic blockers. PTH action was additive to phenylephrine and synergistic with isoproterenol. Sera from uremic parathyroidectomized rats did not effect heart beats, but sera from uremic rats with intact parathyroid glands or from uremic-parathyroidectomized rats treated with PTH had effects similar to PTH. Data indicate that (a) heart cell is a target organ for PTH and may have receptors for the hormone; (b) PTH increases beating rate of heart cells and causes early death of cells; (c) PTH effect appears to be due to calcium entry into heart cells; (d) the locus of action through which PTH induces calcium entry is different from that for catecholamines; and (e) uremic serum has no effect unless it contains PTH. Data suggest that myocardial damage may occur in uremia due to prolonged exposure to very high blood levels of PTH, and assign new dimensions to PTH toxicity in uremia. PMID- 6259215 TI - Increased alpha-adrenergic receptors in ischemic cat myocardium. A potential mediator of electrophysiological derangements. AB - We have recently demonstrated enhanced alpha-adrenergic responsiveness assessed electrophysiologically in ischemic and reperfused myocardium. This study was performed to determine whether ischemia alters alpha 1-adrenergic receptor number (Bmax) of affinity (KD) based on [3H]prazosin binding. Within 30 min after occlusion, Bmax increased in ischemic regions to 207% of control to 27 +/- 2 fmol/mg protein, with the increase persisting (+ 141% of control) during early reperfusion (2 min), before returning to control base-line values (13 +/- 1.6) after 15 min of reperfusion. KD was not altered at any interval studied. Beta receptor number of ([3H]dihydroalprenolol) and Na+-K+ ATPase activity were comparable in control compared to ischemic myocardium although beta-receptor Bmax and KD in both regions decreased during early reperfusion. Thus, the enhanced alpha-adrenergic responsivity previously recognized with ischemia and reperfusion is correlated with an increase in alpha 1-adrenergic receptors. PMID- 6259216 TI - Effect of SQ 14225, an inhibitor of angiotensin I-converting enzyme, on the granulomatous response to Schistosoma mansoni eggs in mice. AB - Murine schistosomiasis is a granulomatous disease associated with high serum and granuloma angiotensin I-converting enzyme (ACE) activity. SQ 14225, a specific competitive inhibitor of ACE, was administered to normal mice and mice infected with Schistosoma mansoni to determine whether this compound could inhibit granuloma ACE activity and modify the size of the granulomatous response to schistosome eggs. Peroral administration of SQ 14225 for 5 wk to infected mice with peak granulomatous responses decreased ACE activity in isolated liver granulomas. Treated mice demonstrated a decrease in granuloma size in the liver, colon, and ileum, and hydroxyproline concentration of isolated liver granulomas was increased. Mean diameters of synchronous pulmonary granulomas, induced by the pulmonary embolization of schistosome eggs into normal and sensitized mice, were decreased by a similar dose of SQ 14225. Withdrawal of SQ 14225 from unsensitized mice with 2-wk-old synchronous pulmonary granulomas induced an increase in inflammation. Infected, but not normal mice receiving SQ 14225 demonstrated reduced portal pressure, liver weight, and body weight. Both normal and infected mice experienced dipsogenesis, expanded intravascular volume, and increased serum ACE. These observations suggest that SQ 14225 can partially inhibit the granulomatous response to schistosome eggs and the pathological manifestations of schistosomiasis. It is possible that ACE has an inflammatory role in granulomatous inflammation. PMID- 6259218 TI - An EM analysis of the synaptic connections of horseradish peroxidase-filled stalked cells and islet cells in the substantia gelatinosa of adult cat spinal cord. PMID- 6259217 TI - Antagonism between epidermal growth factor and phorbol ester tumor promoters in human breast cancer cells. AB - It has been suggested that the phorbol ester tumor promoters act via the receptor effector system for epidermal growth factor (EGF), since they interact with the EGF receptor system and mimic many of the effects of EGF in cultured cells. We have studied the interaction of phorbol esters with the EGF-responsive MCF-7 human breast cancer cell line. Similar to other systems, phorbol esters inhibit EGF binding in MCF-7 cells in a manner paralleling their potency as tumor promoters in mice. The effect is specific for EGF since the membrane binding of insulin is unaffected. Like EGF, the potent phorbol ester 12-O-tetradecanoyl-13 phorbol acetate (TPA) stimulates protein synthesis as indicated by a twofold increase in [(3)H]leucine incorporation into protein after 24 h in TPA. Cell morphology, however, is significantly different with TPA treatment. After 24-48 h in TPA, cells become markedly enlarged with increased cytoplasmic vacuolization and increased membrane microvilli. This is reflected in a fourfold increase in the protein/DNA ratio (control 13.1; TPA 55.9). Furthermore, TPA inhibits cell division in media with or without serum, and prevents growth stimulation by EGF. Low TPA concentrations (1.0 ng/ml) are active, and 10 ng/ml results in maximal inhibition of cell replication. Other phorbol esters inhibit MCF-7 cells relative to their tumor promoting activity in vivo and their ability to inhibit EGF binding in these cells. After 24 h in TPA, incorporation of [(3)H]thymidine into DNA is markedly reduced and the thymidine labeling index falls (33% to 2%) indicating very few S-phase cells. Growth inhibition is reversible by removing TPA from the medium. Similar inhibitory effects are seen with the two other human breast cancer cell lines studied, ZR75-1 and MDA-MB-231. In conclusion, phorbol esters may interact with the EGF receptor domain in MCF-7 human breast cancer cells, but they have distinct effects on cell morphology and growth suggesting alternative pathways of action. The antineoplastic activity of these compounds needs further investigation. PMID- 6259219 TI - Late subcutaneous fibrosis following megavoltage radiotherapy. AB - A woman who received radiotherapy for a breast carcinoma developed symptomatic deep subcutaneous fibrosis 7 months after treatment. Deep biopsy confirmed the diagnosis. A good response to prednisone therapy was obtained in this patient. Long-term sequelae may include soft tissue sarcoma. PMID- 6259220 TI - Opiate antagonists and long-term analgesic reaction induced by inescapable shock in rats. AB - Five experiments examined the influence of opiate antagonists on both the short term analgesic reaction resulting 30 min after exposure to inescapable shock and the long-term analgesic reaction resulting after reexposure to shock 24 hr after inescapable shock exposure. Experiment 1 showed that the long-term analgesic reaction could be reduced by administration of naltrexone prior to exposure to inescapable tail shock. Experiment 2 showed that the reduction in the long-term analgesic reaction produced by naltrexone was dose-dependent. Experiment 3 showed that the long-term analgesic reaction could also be reduced by administration of naltrexone prior to reexposure to shock. Experiment 4 showed that the long-term analgesic reaction could be reduced by administration of large dose of naloxone prior to reexposure to shock. Experiment 5 showed that the short-term analgesic reaction was reduced by naltrexone administered prior to inescapable shock. Some implications of these results for the biochemical substrates of both learned helplessness and stress-induced analgesia are discussed. PMID- 6259222 TI - Addition of sodium bicarbonate to rations of pre- and postpartum dairy cows. AB - Sodium bicarbonate was added to complete mixed rations to evaluate the effect of buffer addition on adaptation to high-energy rations by dairy cows in elderly lactation. Forty-five Holstein cows were assigned to one of three treatment groups: control pre- and postpartum; control prepartum, buffer postpartum; and buffer pre- and postpartum. Rations consisted of 85% chopped grass hay: 15% concentrate prepartum and 60% corn silage:40% concentrate postpartum. On day 4 postpartum, cows were switched abruptly to the postpartum ration for 9 wk. Buffered rations contained .6% sodium bicarbonate prepartum and .7% postpartum. Daily dry matter intake as a percent of body weight for cows fed buffer postpartum (3.51%) was greater than for cows fed no buffer (3.04%) of buffer pre- and postpartum (3.14%). Average production of 4% fat-corrected milk was greater for cows fed buffer postpartum and buffer pre- and postpartum (31.9 kg/day and 31.7 kg/day) than for cows fed no buffer (28.9 kg/day). Milk fat tests were not different. Cows fed the buffered rations lost body weight between wk 1 and 9 as compared to a net gain for cows fed no buffer. Cows fed buffers consumed more dry matter during wk 1 than did cows fed no buffer. Samples of rumen fluid, feces, and serum showed few differences that could be attributed to treatments. Compared to controls, cows fed sodium bicarbonate adapted to rations more rapidly postpartum as indicated by increased feed intake during the first 2 wk and by increased milk production during the first 4 wk of the trial. PMID- 6259223 TI - Woodpulp fines or corn silage as roughages in complete rations or a pelleted complete ration for young dairy replacements from birth through 18 weeks of age. AB - Holstein calves, 18 females and 12 males, were assigned randomly to 10 blocks of 3 calves each by sex, and within each block were assigned randomly to one of three experimental rations. All calves received sour colostrum from day 1 through day 35. The respective dry rations were offered beginning at day 8. The three rations consisted of (dry basis): 1) 11% woodpulp fines and 89% concentrate; 2) 33.7% corn silage and 66.3% concentrate; and 3) a commercially available pelleted complete ration. From birth through 8 wk, calves fed woodpulp gained more weight than those fed silage and approximately equal weight to calves fed commercial ration. From 8 through 18 wk. calves fed the latter gained more weight than other calves. Dry matter intake followed the same order as weight gain. Blood samples were obtained biweekly beginning with the 2nd wk from the jugular vein of each calf. There were no differences in glucose 2 through 18 wk. Urea nitrogen of plasma was greater in calves fed commercial ration than in other calves in six of the sampling periods. Calves fed silage had more urea nitrogen in plasma than calves fed woodpulp for three of the sampling periods. Rumen tissue from male calves at 18 wk fed woodpulp showed the most normal appearance in papillae color, density, and length. Calves fed silage had rumen tissue showing short, black, nodular papillae. Calves fed commercial ration showed long, branched, necrotic papillae that were keratotic and loosely attached. PMID- 6259221 TI - Observations on the level of cyclic nucleotides in three population of human lymphocytes in culture. AB - The level of cyclic nucleotides in three populations of cultured human lymphocytes were studied. An early conspicuous elevation of c-GMP level and a reciprocal relationship between c-AMP and c-GMP fluctuations were demonstrated in T cells from normal donors. Null cells from patients with ALL showed a constantly low level of c-AMP, while c-GMP fluctuated in apparent relationship with cell doubling time. Persistently low levels of c-AMP and persistently high level of c GMP were found in B cells from patients with CLL. Possible significance of these findings is discussed. PMID- 6259225 TI - Evaluation of an alfalfa silage-corn silage roughage feeding program for raising dairy heifers. AB - One hundred and ninety-seven dairy heifers, which included a Holstein line, an Ayrshire line, and a reciprocal cross line, were assigned randomly to two forage treatments at 57 days of age. Forages fed to control heifers consisted of 40% grass-legume hay, 20% wilted grass silage, and 40% corn silage (dry matter). The second, or silage group, was fed a dry matter mixture of 40% corn silage and 60% direct cut alfalfa silage, formic acid treated. Both groups of heifers were fed the same quantity of calf starter and calf grower rations. In general, heifer weight and size were greater with the all-silage forage. At 350 and 574 days of age, heifers on the all-silage ration were heavier than their controls. Heifers fed the all-silage ration had greater heart girths and wither heights. Reproductive performance, as measured by the number of services per conception, was not significantly different in the two treatment group. There were no health problems that could be attributed directly to dietary treatment. Dairy heifers were reared successfully on a forage mixture of corn silage and formic acid treated alfalfa silage when additional concentrate was fed during the 1st yr. PMID- 6259224 TI - Woodpulp fines or corn silage as roughages in complete rations or a pelleted complete ration for young dairy replacements 18 through 36 weeks of age. AB - Twenty-eight Holstein calves were fed one of three experimental diets from 18 through 36 wk: 1) 50% woodpulp fines, 25% corn silage, and 25% concentrate; 2) 75% corn silage and 25% concentrate; and 3) a commercially available, pelleted, total calf ration. The first two rations were equivalent in roughage, vitamin, and mineral content, and all three rations were equivalent in crude protein. Average daily gain (kg), dry matter intake (% of body weight), and feed/gain for calves fed the three rations were .92, 2.42. 6.28; 1.10, 2.29, 4.07; and 1.12, 3.16, 6.73. Glucose (mg/100 ml), urea nitrogen (mg/100 ml), and B-hydroxybutyrate (mg/100 ml) in plasma from calves at 23 wk were 72.0, 5.2, .7; 72.5, 5.1, 1.9; and 82.4, 12.3, .8. The amount of butyrate (% of total), acetate/propionate, and pH of the rumen fluid from calves at 23 wk were 6.31, 2.79, 6.99; 11.74, 2.76, 7.05; and 9.89, 2.04, 6.73. Papillae length (cm) and density/cm2 ofa the rumen tissue from male calves by biopsy were: 1.83, 48.5; 2.12, 67.1; and 2.12, 27.6. Corn silage and woodpulp fines or corn silage alone can be fed to dairy calves in complete rations with satisfactory results from 18 to 36 wk of age. Additional experimentation is required to optimize quantities and proportions of these roughages in complete rations for young heifers. PMID- 6259227 TI - The relationship between inflammation and cAMP level in human gingiva. AB - The levels of cAMP were measured by means of radioimmunoassay in 20 gingival samples free from inflammatory cells and 43 samples with moderately dense and dense aggregations of inflammatory cells. The average values were found to be 340 +/- 44 and 552 +/- 59 pmol/gm wet tissue, respectively. The increase in cAMP levels in inflammation is suggested to be modulated by an increase in endogenous prostaglandin synthesis and could be one of the natural mechanisms by which the host protects itself from dangerous consequences of unregulated immune response. PMID- 6259226 TI - Long-term performance and health cows experimentally exposed to polybrominated biphenyls. AB - Fifteen Holstein cows were studied for up to 15 00 days to determine whether exposure to polybrominated biphenyls produced latent or subtle toxicosis not evident in previous acute or short studies. Animals for these long studies came from three groups given 0, .25, or 250 mg of fireMaster BP-6 per day for 60 days in 1975. Another group that received 250 mg of BP-6 for 180 or 202 days in 1976 also was studied. Individual animals were in their second, third, or fourth lactations. Milk production was not different among experimental groups, and mature body weights were similar. Increases in the amount or duration of exposure did not increase number of infections, dysfunctions, or general injuries. Exposure to 250 mg/day for 60, 180, or 202 days increased frequencies of reproductive disorders at parturition, particularly related to and following a high incidence of dystocia. A contributing factor to dystocia was larger birth weights of calves from cows exposed to 250 mg daily as compared to calves from cows exposed to 0 or .25 mg polybrominated biphenyls. Although reproductive dysfunctions required more veterinary care, numbers of services per conception were not different among groups. PMID- 6259228 TI - Isolated parotid acinar cells from patients with cystic fibrosis. Functional characterization. AB - Studies of the homeostasis and secretory function of isolated parotid acinar cells from patients with cystic fibrosis were conducted. It was demonstrated that the transmembrane fluxes of Na and the muscarinic cholinergic receptor stimulus secretion coupling were depressed, while the stimulus-secretion coupling of the beta-adrenergic receptor was hyper-reactive. PMID- 6259229 TI - Thiocyanate as a cofactor in myeloperoxidase activity against Streptococcus mutans. AB - Inhibition of glycolysis of some oral bacteria was established in vitro by an antibacterial system, consisting of myeloperoxidase, H2O2, and a cofactor. When thiocyanate was used in physiological concentration as a cofactor, the system acted (at low pH) bactericidally on Streptococcus mutans, as indicated by the determination of viable counts. However, at neutral pH, the glycolysis of Streptococcus mutans was inhibited, while its viability remained unaffected. The possible role of such a pH-dependent antibacterial system in the oral cavity is discussed. PMID- 6259230 TI - Cancers, precancers, and pseudocancers on the male genitalia. A review of clinical appearances, histopathology, and management. AB - Leukoplakia penis and balanitis xerotica obliterans are precancerous lesions. Bowen's disease, erythroplasia (Queyrat), and extramammary Paget's disease are carcinomas in situ. Lesions of both types may closely mimic benign skin conditions that may occur in the genital region. Histologic examination is usually the only certain means of diagnosis. The same considerations apply to pseudomalignancies, e.g., giant condyloma acuminatum (Buschke-Loewenstein), which clinically behaves as a carcinoma but histologically appears benign, and Bowenoid papulosis, a new entity that is believed to be benign although it has histologic features of a carcinoma in situ. PMID- 6259231 TI - Mass medication with aspirin and platelet aggregation. PMID- 6259232 TI - Responses of medical women to a survey on sexist language in medical publications. PMID- 6259233 TI - Women psychiatrists triumph at American Psychiatric Association. PMID- 6259234 TI - The women: who, where, when and why: a long-term follow-up study of women from two medical schools. PMID- 6259235 TI - Women in medicine--a historical perspective. PMID- 6259236 TI - "On the same terms precisely": the women's medical fund and the Johns Hopkins School of Medicine. PMID- 6259237 TI - Fulfilling the promise: Hopkins women before World War II. PMID- 6259238 TI - Little choice and a stimulating environment. PMID- 6259239 TI - Similarities and differences between men and women as students. PMID- 6259240 TI - A follow-up study of Harvard Medical School graduates, 1967-1977. PMID- 6259242 TI - Women in medicine, 1979: what are the issues? PMID- 6259241 TI - The status of women in medicine: background data. PMID- 6259243 TI - The impact of women physicians on social change in medicine: the evolution of humane health care delivery systems. PMID- 6259244 TI - The distaff of Aesculapius--the married woman as physician. PMID- 6259245 TI - Fast stopped-flow microcalorimeter. AB - A fast stopped-flow microcalorimeter using a thermistor and an a.c. bridge is described. Time resolution, limited by the response of the thermistor, is 3 ms for t 1/2 while sensitivity is 100 mu degree C in this bandpass. A reaction requires 0.3 ml of each reactant. The microcalorimeter is adiabatic to within 2% for 2 s and mixing may be repeated every 5 min. Computer finite element simulation techniques (FEST) are used to correct for the thermistor response time and heat losses. Results of tests with reactions of NaOH and HCl, NaHCO3, and HCl, and glyclyglycine and CO2 agree with published kinetic and thermodynamic values to within an experimental error of less than 2%. PMID- 6259246 TI - Centrifugal assessment of cell adhesion. AB - The design of a chamber for determining the centrifugal force necessary to detach cells from various substrates is presented. Cells from an SV40-transformed murine peritoneal macrophage line and human erythrocytes were used to assess the feasibility of using the chamber for studies of cell adhesion. This work was confirmed the usefulness of the chamber and provided data concerning the force necessary to detach the cells. These data indicated that the percentage of cells detached from a glass substrate was not a function of force alone. The number of cells detaching increased with the impulse applied to the cells when they were exposed to a constant force. Similarly, when the impulse applied to the IC21 cells was maintained at a constant level, the percentage of cells detached by a centrifugal force increased with the magnitude of the force. PMID- 6259247 TI - [Fabry's disease in ophthalmology (author's transl)]. AB - The authors report a new case of Fabry's disease and emphasize the easiness of diagnosis on simple slit lamp examination of the affected males and conductor females. This disease is transmitted as X linked so that both heterozygotes and hemizygotes show a corneal storage known as cornea verticillata. The clinical features are completed by a conjunctival biopsy and the electron microscopy study shows lamellar bodies in the lysozomes. PMID- 6259248 TI - Evaluation of polyurethane foam as a trapping medium for herbicide vapor in air monitoring and worker inhalation studies. AB - Polyurethane foam was an efficient adsorbent for trapping vapors of butyl esters of 2,4-D (2,4-dichlorophenoxyacetic acid) and triallate (S-(2,3,3 trichloroallyl)diisopropylthiocarbamate) in high volume air monitoring studies and of butyl esters of 2,4-D, iso-octyl ester of 2,4-D, n-butyl ester of 2,4,5-T (2,4,5-trichlorophenoxyacetic acid), bromoxynil octanoate (2,5-dibromo-4 hydroxybenzonitrile), triallate, and trifluralin (alpha, alpha, alpha-trifluoro 2,6-dinitro-N-N-dipropyl-p-toluidine) in short-term, low volume, worker inhalation exposure studies. The collected herbicide vapor was readily desorbed under soxhlet extraction with n-hexane and subsequently analyzed with electron capture GLC. The overall efficiencies, for both trapping and extraction, were over 90%, using a single plug, for all herbicides, except triallate. In the case of triallate, two plugs in series were required for efficient trapping under the high volume air monitoring situation. PMID- 6259249 TI - Circadian rhythmicity of ACTH and corticosterone in the rat. AB - The circadian secretion of ACTH and corticosterone was assessed by measuring immunoreactive ACTH concentration in the plasma and ACTH content in the anterior and posterior pituitary over a 30 h period in groups of both male and female rats and comparing these data to fluorometric corticosterone concentration in the plasma and corticosterone content in the adrenal. A circadian rhythm of plasma corticosterone levels and adrenal content was apparent in both males and females with the highest levels at the onset of darkness. In contrast, there was no significant circadian rhythm in plasma ACTH levels or anterior or posterior ACTH pituitary content. Because the ACTH and corticosterone rhythms were dissociated, rhythmic corticosterone secretion is not entirely dependent on ACTH secretion. PMID- 6259251 TI - Investigation of the usefulness of the plasma adenosine 3' 5' - cyclic monophosphate response to glucagon in thyroid disease. AB - The plasma adenosine 3', 5' - cyclic monophosphate (cyclic AMP) response to 50 micrograms of intravenous glucagon was examined in 14 normal euthyroid subjects, 15 patients with thyrotoxicosis and 5 patients with myxedema. The cyclic AMP responses to 50 micrograms of intravenous glucagon was significantly higher in the hyperthyroid group than in the euthyroid or hypothyroid group. However, the areas of overlap between all three groups were large and there was little relationship between the plasma cyclic AMP response to glucagon and the biochemical assessment of thyroid function. Serial studies of the response to 50 micrograms glucagon were carried out in four patients receiving treatment for thyrotoxicosis. Again, there was not consistent relationship between the plasma cyclic AMP responsiveness to glucagon and the free thyroxine index. It is concluded that although the plasma cyclic AMP response to glucagon is increased in thyrotoxicosis and decreased in myxedema, the variability of this response in thyroid disease precludes its use as a tissue index of thyroid hormone responsiveness. PMID- 6259252 TI - Adrenocortical responses to adrenocorticotrophin in the hypophysectomized ovine fetus. AB - Fetal adrenocortical responsiveness to ACTH declines during 90-120 days gestation and fetal pituitary peptides have been implicated in this refractoriness. In these studies the ACTH-induced cortisol responses were measured in 11 ovine fetuses of 114 days gestation. Five animals were hypophysectomized as evidenced by prolonged gestation, pituitary histology, TRH-testing, delayed maturation and decreasing fetal plasma prolactin concentrations (less than 1 ng.ml-1) (P less than 0.005). Resting cortisol concentrations decreased from 22.4 to 8.1 ng.ml-1 in the hypophysectomy group and were not different from the control group (19.6 14.9 ng.ml-1) over the 5 days of study. Responses measured as increments in plasma cortisol concentrations increased equally and successively in both groups. Since pituitary ablation fails to enhance fetal adrenal responsiveness to ACTH we conclude that refractoriness is unlikely to be caused by an inhibitor of pituitary origin. PMID- 6259250 TI - Effect of propranolol on aldosterone response to heat exposure in sodium restricted men. AB - To assess the role of the renin-angiotensin system in the control of aldosterone reease in response to heat exposure, 6 sodium restricted subjects were studied on three random experimental days: a control day and two heat exposure days (46C, 35 mbar, 90 min) with and without propranolol. Plasma aldosterone, renin activity, ACTH and K+ were determined from plasma samples taken every 20 min from 08:00 to 14:00. After propranolol administration, plasma aldosterone responsiveness to heat exposure increased, though plasma renin activity was depressed. Concurrently, propranolol reduced heat tolerance, leading to an increased ACTH and cortisol release in 3 of the subjects. Plasma levels of K+ were not significantly different during both heat exposure days. The enhanced response of plasma aldosterone may in part be related to the concurrent rises in ACTH, but a similar sustained aldosterone response was observed in subjects without ACTH release. Except for a significantly lower heart rate, propranolol induced no changes in hemodynamic and thermal response to heat. Plasma volume, blood pressure, sodium excretion, mean skin and rectal temperature rises and body weight losses were not modified by prior administration of the drug. The dissociation between aldosterone and renin activity after propranolol administration suggests that the aldosterone response to heat exposure is not primarily mediated by changes in activity of the renin-angiotensin system. Propranolol may lead to a reduced metabolic clearance rate of aldosterone or increase the sensitivity of the adrenal cortex to concomitant changes in the known stimuli, but the involvement of an additional factor in aldosterone regulation during heat exposure cannot be excluded. PMID- 6259253 TI - The effect of succinylcholine on denervated skeletal muscle. AB - Succinylcholine, commonly used in anesthesia, paralyzes normal skeletal muscles by blocking transmission at the myoneural junction, but in denervated muscle, it produces sustained muscle contractions lasting several minutes. This denervation hypersensitivity, believed to be due to the progressive enlargement of the receptor area, begins within 2 to 3 weeks and may last for months. Three patients with denervation hypersensitivity were studied: one with isolated denervation of the flexor pollicis longus and two with combined median and ulnar nerve palsy. Within 1 to 2 minutes after administration of succinylcholine, sustained contraction of the denervated muscles occurred and lasted 4 to 5 minutes. Succinylcholine, due to its ability to produce sustained muscle contraction in denervated muscles, may be a useful diagnostic aid in distinguishing loss of function due to nerve injury from tendon disruption. PMID- 6259254 TI - Congenital central hand deficit. AB - A retrospective study of 60 patients in whom 80 hands demonstrated a congenital central deficity showed that 23% also had central foot deficits and 15% had a family history of similar hands. The hands are classified based on absence of one, two, or three central rays. The long ray is most affected, followed by the index and ring rays. Many also had lesser deficiencies in border rays. Surgery was performed on the central or border ray structures in 58% of the hands. Function of the hand cannot be predicted from its anatomic state. These patients did not consider their central deficits as a social catastrophe. PMID- 6259255 TI - Immunocytochemical localization of receptor-bound human chorionic gonadotropin in pseudopregnant rat ovaries. AB - Localization of receptor-bound human chorionic gonadotropin (hCG) in pseudopregnant rat ovarian cells was studied by the peroxidase-antiperoxidase (PAP) complex method. The animals were injected, 2,6,12, and 24 hr prior to killing with a single intravenous dose of hCG. The hormone localized to the periphery of the luteal and interstitial glandular cells. The luteal cells seemed to bind different amounts of the hormone, which suggests that the number of receptor varies from one cell to another or that the receptors are not similarly accessible to the circulating hormone in all cells. The hormone seemed to disappear unequally from the luteal cells, possibly due to the variable amounts of primarily bound hormone or to different removal mechanisms. The hormone was distributed unevenly at the luteal cell periphery. This observation supports previous findings that hCG preferentially binds to the cell surface regions directed towards the capillary areas. Compatible results were obtained with anti hCG serum and with antisera against the hCG subunits. Our results support the previous autoradiographic evidence of the plasma membrane localization of luteinizing hormone receptor in the luteal cells, and are compatible with the concept that only a small fraction of the receptor-hormone complexes may be internalized. PMID- 6259256 TI - Cell-mediated immunity in herpes simplex virus-infected mice: H-2 mapping of the delayed-type hypersensitivity response and the antiviral T cell response. AB - An adoptive transfer system was used to investigate the H-2 restriction of delayed-type hypersensitivity (DTH) to herpes simplex virus. A successful DTH transfer was achieved when donor and recipient were compatible at the I-A region, with K and D region compatibility unnecessary. However, the rapid clearance of infectious virus from the inoculation site was found only when the donor and recipients were compatible at H-2K (and presumably D) and I-A regions. PMID- 6259257 TI - The myeloperoxidase-hydrogen peroxide-halide system as effector of neutrophil mediated tumor cell cytotoxicity. PMID- 6259258 TI - Oxidation of n-formyl methionyl chemotactic peptide by human neutrophils. AB - Human neutrophils during phagocytosis oxidized the synthetic chemotactic peptide, n-formyl methionyl-leucyl-phenylalanine (n-FMLP), to its sulfoxide derivative (n FMsLP). The oxidation of n-FMLP by phagocytosing neutrophils was inhibited by methionine, but not by methionine sulfoxide, leucine, or phenylalanine, confirming that it was the methionine moiety of n-FMLP that was oxidized. The oxidation of n-FMLP was also inhibited by myeloperoxidase inhibitors or catalase, but not by SOD or mannitol, suggesting the involvement of the myeloperoxidase system. Since n-FMsLP does not have chemotactic activity, the oxidation of n-FMLP by phagocytosing neutrophils may be one mechanism by which neutrophils modulate the inflammatory process. PMID- 6259259 TI - Plasminogen activator is an apparent lymphocyte mitogen. AB - Culture fluids of avian sarcoma virus (ASV)-transformed but not normal chicken embryo cells frequently elicited a mitogenic response in normal avian and murine lymphocytes. We examined the possibility that plasminogen activator (PA) might be responsible for the observed mitogenic effect. PA activity, present in culture medium, was correlated positively with lymphocyte mitogenic capacity. Treatment of cells with phorbol myristate acetate, which elevates PA levels, increased mitogenesis. Similar treatment with dexamethasone, which inhibits PA biosynthesis and/or secretion, reduced lymphocyte mitogenic activity. Addition to culture fluids of either benzamidine or diisopropylfluorophosphate, both specific PA inhibitors, blocked lymphocyte proliferative responsiveness to culture fluids. In contrast, neither epsilon-amino-caproic acid nor trasylol, which inhibits plasmin esterase activity but not PA, abrogated lymphocyte responsiveness. Furthermore, purified urokinase, an enzyme of similar substrate specificity to PA, had lymphocyte stimulatory activity. These results strongly suggest that PA can function as a lymphocyte mitogen. PMID- 6259261 TI - The threat of mouse pox. PMID- 6259260 TI - Neutralization of vesicular stomatitis virus (VSV) by human complement requires a natural IgM antibody present in human serum. AB - Neutralization of VSV by human serum ws previously shown to involve C1, C2, C3, and C4 of the classical complement (C) pathway. All normal human sera tested were equivalently active in this regard. However, purified C1, C2, C3, and C4 were unable to mediate VSV neutralization. In the present studies an additional factor required for C-mediated neutralization was isolated from normal human serum and identified as a natural IgM antibody specific for a viral encoded antigen. Purified IgM bound to the virus and formed a complex that activated component C1. Normal serum concentrations of purified IgM, C1, C2, C3, C4 neutralized VSV to the same extent as normal serum. Purified IgM did not neutralize VSV alone or in conjunction with C1, C2, and C4. Inclusion of C3 resulted in full neutralization and C3b binding to the virus was demonstrated. Thus, normal human serum contains a natural antibody of the IgM class that is directed toward a viral antigen. The antibody facilitates neutralization by forming an immune complex that activates C1 and thus efficiently initiates the classical pathway at the viral surface. Neutralization occurs with C3b deposition on the viral envelope and probably results from a blanket of C protein that interferes with viral attachment to susceptible cells. PMID- 6259262 TI - Isolation of human monocytes on re-orienting gradients of Percoll. AB - We have developed a rapid and simple method for isolating monocytes from peripheral blood. After mononuclear cells are isolated on a Ficoll-Hypaque gradient, the monocytes are purified by sedimentation for 5 min through a re orienting gradient of Percoll. The method is easily reproducible and yields approximately half of the monocytes in staring blood, with minimal contamination by lymphocytes. Although both monocytes and lymphocytes have similar densities, separation occurs because these cells migrate at differing rates through the gradient to reach their equilibration point. The recovered monocytes are viable and functional; over 95% of them exclude trypan blue and they adhere to glass and plastic and ingest latex particles normally. By virtue of the rapidity and gentle nature of its centrifugation steps, the method exposes cells to only very limited non-physiologic conditions. For this reason and because the monocytes are maintained in suspension, opportunities for functional alterations are minimized. PMID- 6259264 TI - [Clinical, pathophysiological, and therapeutic studies on familial amyloidotic polyneuropathy (author's transl)]. PMID- 6259263 TI - Inhibition of epidermal adenyl cyclase by lithium carbonate. AB - An in vitro floating system was used to investigate the effect of lithium carbonate (Li2CO3) on the activity of adenyl cyclase in normal pig epidermis. Li2CO3 decreased the responsiveness of adenyl cyclase to stimulation by histamine, adenosine monophosphate (AMP) and epinephrine. This abnormality is similar but not identical to the previously described impaired responsiveness of adenyl cyclase to epinephrine and PGE2 in psoriatic plaques compared to normal adjacent skin. Involved and uninvolved skin from a psoriatic on lithium therapy demonstrated decreased responsiveness to in vitro stimulation by epinephrine, histamine and adenosine when compared to skin from psoriatics who were not on lithium therapy. These results are consistent with the observation that lithium therapy worsens psoriatic lesions. PMID- 6259265 TI - The effect of complete biliary obstruction on bile secretion. Studies on the mechanisms of postcholestatic choleresis in the rat. AB - It has been previously shown that rats subjected to obstructive cholestasis demonstrate in the postcholestatic period, after release of common duct obstruction, a marked increase in canalicular bile flow relative to bile acid excretion. To characterize this phenomenon further, we investigated whether changes in canalicular permeability and in the activity of (Na+-K+)-ATPase in isolated liver surface membranes are associated with postcholestatic choleresis. With this purpose, the clearances of 14C-erythritol and 3H-insulin were simultaneously measured in rats subjected to a 3-day obstructive cholestasis and in controls, during spontaneous choleresis as well as during the intravenous infusion of sodium taurocholate at both submaximal and saturating rates. In additional groups of bile duct-ligated rats and controls, liver surface membrane fractions were isolated, and the activity of appropriate marker enzymes and (Na+ K+)-ATPase was determined. In both groups 14C-erythritol clearance closely approximated total bile flow, suggesting that bile flow was of canalicular origin. However, cholestatic rats showed a sixfold increase in 3H-inulin clearance compared to controls. These results suggest that canalicular permeability to inulin is markedly increased in cholestatic rats. On the other hand, (Na+-K+)-ATPase activity was significantly higher in cholestatic rats than in controls in both homogenate (1.27 +/- 0.07 and 0.89 +/- 0.07 U/mg of protein, respectively, p less than 0.001) and liver surface membranes (22.6 +/- 1.2 and 17.5 +/- 1.2 U/mg of protein, respectively, p less than 0.001). Thus enhanced choleretic response to bile acids in the postcholestatic period is associated with an increased permeability of canalicular structure to inulin and with a significant increase in both homogenate and surface membrane (Na+-K+)-ATPase activity. In addition, this study points out some important differences between bile secretory function of rats subjected to obstructive cholestasis and that described in models of bile secretory failure induced by drugs or monohydroxy bile acids. PMID- 6259266 TI - Comparison of binding of bovine and human thyroid-stimulating hormone to receptor sites on human thyroid membranes. AB - The binding of 125I-labelled bovine TSH (bTSH) to a wide range of human thyroid membrane preparations was compared with that of 125I-labelled human TSH (hTSH). Much higher binding percentages were obtained with the 125I-labelled bTSH. This was because the receptors had a higher binding affinity for bTSH than for hTSH. No differences in tracer purity, nor differences in optimal conditions for the binding of bTSH or hTSH, nor tracer degradation contributed significantly to the better binding of 125I-labelled bTSH. Good correlation was found between binding percentages for 125I-labelled bTSH and 125I-labelled hTSH over the range of thyroid specimens. Useful information on human TSH receptors is, therefore, obtainable from binding studies with 125I-labelled bTSH. The TSH displacement curves yielded linear Scatchard plots whenever the tracer and displacing hormones were of the same species. The data were, therefore, consistent with a simple binding reaction between TSH and a single set of independent receptor sites. PMID- 6259267 TI - Brain adrenocorticotrophin after adrenalectomy and sham-operation of rats. AB - The influence of adrenalectomy on the level of immunoreactive 18-24 ACTH extracted from hypothalamus, hippocampus and pituitary gland of rats was investigated. Brain ACTH was further characterized by fractionation by gel permeation chromatography. Porcine 1-39 ACTH was exposed to synaptic plasma membranes in vitro in order to evaluate the role of metabolic conversion in changes of brain ACTH content. Removal of the adrenals, when compared with sham adrenalectomy, resulted in a transient depletion of ACTH content in the anterior pituitary gland and the hippocampus, but not in the hypothalamus and the neurointermediate lobe. However, sham-adrenalectomy caused a transient reduction in levels of ACTH when compared with levels before operation in all tissues studied. The effects of adrenalectomy on hippocampal ACTH content persisted in hypophysectomized rats. Treatment of adrenalectomized rats with corticosterone failed to restore the reduced ACTH content when it was administered in doses that completely suppressed the release of pituitary ACTH. Adrenal steroids, however, may exert a direct effect on the metabolism of ACTH in the brain as judged from the in-vitro studies with porcine 1-39 ACTH exposed to a synaptosomal plasma membrane fraction of hippocampal tissue. The present study suggests that control of brain ACTH occurs independently of the control of pituitary ACTH release. PMID- 6259268 TI - Independent down-regulation of insulin and calcitonin receptors on a human tumour cell line. AB - A human lung cancer cell line (BEN cells) with a calcitonin receptor and calcitonin-responsive adenylate cyclase also possesses an insulin receptor. This has been characterized and found to have properties similar to those of other mammalian cell insulin receptors. A receptor number of 58 000 per cell was calculated from curvilinear Scatchard plots, and dissociation of bound labelled insulin by dilution was facilitated by the addition of unlabelled insulin, consistent with negatively co-operative interactions among binding sites. Preincubation of cells with either calcitonin or insulin led to loss of hormone binding in washed cells. In the case of calcitonin this was associated with loss of adenylate cyclase response. For each hormone the state of down-regulation was characterized by a decrease in receptor number, and for calcitonin there was also a low in sensitivity of adenylate cyclase. Down-regulation to calcitonin was more rapid than that to insulin and in each case recovery had occurred by 16 h after removal of the hormone. Induction of down-regulation was specific, in that preincubation with one hormone did not influence the subsequent binding or response of the other. Such data are consistent with independent modulation of peptide receptors in the same cell. PMID- 6259269 TI - Protein phosphorylation and the regulation of cation cotransport. AB - The turkey erythrocyte is a useful system in which to investigate the relationship between protein phosphorylation and membrane transport. This cell possesses a catecholamine- and cyclic AMP-stimulated Na+-K+ 'cotransport' system in its plasma membrane, and the physiological properties of this system have been partially elucidated. It is distinct from the Na+-K+ 'pump' and is insensitive to ouabain, but can be blocked by certain diuretic agents such as furosemide and bumetanide. A plasma membrane protein of MW 230000, called goblin, has been identified as the major protein whose state of phosphorylation increases upon incubation of turkey erythrocytes with catecholamines or cyclic AMP. The kinetics of phosphorylation of goblin at its cyclic AMP-sensitive sites correlate well with the kinetics of Na+-K+ cotransport activation under various conditions. This protein may play a role in the regulation of the Na+-K+ cotransport system by catecholamines and cyclic AMP. PMID- 6259270 TI - A cellular basis for the differences in regulation of synthesis and secretion of ACTH/endorphin peptides in anterior and intermediate lobes of the pituitary. AB - The focus of research in our laboratory over the past few years has been the regulation of synthesis, processing and release of the ACTH/LPH family of peptides. These peptides are derived from a common precursor protein that is found in both the anterior and intermediate lobes of the pituitary (Roberts et al. 1978) and in the hypothalamus (Liotta et al. 1979). In the anterior lobe this protein gives rise to alpha (1-39)ACTH, beta-lipotropin and an N-terminal fragment of undefined function. In addition, a variety of intermediate lobe pituitary peptides can be derived from the precursor by further processing of ACTH and beta-LPH. In this paper we compare the structure of the precursor in the anterior and intermediate lobes of mouse and rat pituitary. Processing of the precursor to its constituent hormones is then contrasted in primary cultures of anterior and intermediate lobe cells using pulse label and pulse chase techniques with radioactive amino acids and sugars. Finally, we discuss the difference in behaviour of anterior and intermediate lobe cells in culture with regard to their rates of secretion and intracellular turnover of hormones and regulation of these processes by hypothalamic factors, glucocorticoids and catecholamines. PMID- 6259271 TI - Opioid peptides: aspects of their origin, release and metabolism. AB - At the present time there is evidence for two families of related peptides which act as ligands for opiate receptor sites. The endorphin group of peptides are derived from the ACTH/LPH precursor pro-opiocortin. The enkephalins appear to be formed from a separate precursor or precursors that have yet to be fully characterized. There appear to be a number of different types of opiate receptors and this may be related to the multiplicity of peptide ligands that have so far been identified. The enkephalins and related peptides appear to have a much wider distribution than the endorphins but the latter may act as circulating hormones unlike the enkephalins. It is likely that both endorphins and enkephalins are involved in sensory modulation processes and release of these peptides has been demonstrated during brain stimulation for pain relief. The enkephalins are very rapidly inactivated by tissue proteases, the aminopeptidases appear largely responsible for the inactivation of exogenously administered enkephalins but the dipeptidyl carboxypeptidase, termed enkephalinase, may have a special inactivating function at enkephalinergic synapses. Evidence will be presented for the biosynthesis, the release and inactivation of the enkephalins relating to the above points. PMID- 6259272 TI - [The effect of thyroid function on the increase of plasma cyclic AMP following glucagon injection (author's transl)]. AB - The increase in plasma cyclic adenosine-3':5'-monophosphate (cAMP) was measured after intravenous injection of 1 mg of glucagon in 26 normal subjects, 36 patients with hyperthyroidism, 35 patients with hypothyroidism and 24 patients with euthyroid goitre. While patients with euthyroid goitre responded normally, the plasma cyclic AMP response in patients with hyperthyroidism was considerably increased and in those with hypothyroidism decreased. 4 patients with cirrhosis of the liver had reduced responses and 1 patient with extrahepatic obstructive jaundice an enhanced response. This test seems to be a valuable additional parameter for the description of the thyroid-dependent metabolic situation. However, because of its unspecificity it cannot replace the measurement of serum T3, T4 and thyrotropin (TSH) response to thyroliberin (TRH). PMID- 6259273 TI - Influence of calcium on guanosine 3',5'-cyclic monophosphate levels in frog rod outer segments. AB - In the presence of 10(-9) M calcium, rod outer segments freshly detached from dark-adapted frog retinas contain between 0.01 and 0.02 moles of guanosine 3',5' cyclic monophosphate (cyclic GMP) per mole of rhodopsin. The dark level of cyclic GMP is reduced approximately 50% by illumination that bleaches 5 x 10(5) rhodopsin molecules/outer segments. The dark levels of cyclic GMP also can be suppressed to approximately 0.007 mol/mol of rhodopsin by increasing the concentration of calcium from 10(-9) M to 2 x 10(-9) M, and they remain at this level as calcium concentration is raised to 10(-3) M. The final level to which illumination reduces cyclic GMP in unaffected by the calcium concentration between 10(-9) and 10(-3) M. The maximal light-induced decrease in cyclic GMP occurs within 1 s from the onset of illumination at all calcium concentrations. The magnitude and time-course of the light-induced decrease in cyclic GMP measured in these experiments are comparable to values obtained previously (Woodruff et al. 1977. J. Gen. Physiol. 69:677-679; Woodruff and Bownds. 1979. J. Gen. Physiol. 73:629-653). The data are consistent with a role for cyclic GMP in visual transduction irrespective of the calcium concentration. PMID- 6259274 TI - Equilibrium properties of a voltage-dependent junctional conductance. AB - The conductance of junctions between amphibian blastomeres is strongly voltage dependent. Isolated pairs of blastomeres from embryos of Ambystoma mexicanum, Xenopus laevis, and Rana pipiens were voltage clamped, and junctional current was measured during transjunctional voltage steps. The steady-state junctional conductance decreases as a steep function of transjunctional voltage of either polarity. A voltage-insensitive conductance less than 5% of the maximum remains at large transjunctional voltages. Equal transjunctional voltages of opposite polarities produce equal conductance changes. The conductance is half maximal at a transjunctional voltage of approximately 15 mV. The junctional conductance is insensitive to the potential between the inside and outside of the cells. The changes in steady-state junctional conductance may be accurately modeled for voltages of each polarity as arising from a reversible two-state system in which voltage linearly affects the energy difference between states. The voltage sensitivity can be accounted for by the movement of about six electron charges through the transjunctional voltage. The changes in junctional conductance are not consistent with a current-controlled or ionic accumulation mechanism. We propose that the intramembrane particles that comprise gap junctions in early amphibian embryos are voltage-sensitive channels. PMID- 6259276 TI - gamma-Aminobutyric acid receptors in brain postsynaptic densities. AB - Rat brain synaptic plasma membranes contain two receptorlike binding sites for the inhibitory transmitter gamma-aminobutyric acid. Postsynaptic junctional structures (postsynaptic densities) isolated from these membranes contain only the higher affinity site enriched more than sixfold compared to the membranes. The results provide the first direct evidence for the association of transmitter receptors with postsynaptic junctional sites in the brain. PMID- 6259275 TI - Kinetic properties of a voltage-dependent junctional conductance. AB - We have proposed that the gap junctions between amphibian blastomeres are comprised of voltage-sensitive channels. The kinetic properties of the junctional conductance are here studied under voltage clamp. When the transjunctional voltage is stepped to a new voltage of the same polarity, the junctional conductance changes as a single exponential to a steady-state level. The time constant of the conductance change is determined by the existing transjunctional voltage and is independent of the previous voltage. For each voltage polarity, the relations between voltage, time constant, and steady-state conductance are well modeled by a reversible two-state reaction scheme in which the calculated rate constants for the transitions between the states are exponential functions of voltage. The calculated rate constant for the transition to the low conductance state is approximately twice as voltage dependent as that for the transition to the high-conductance state. When the transjunctional voltage polarity is reversed, the junctional conductance undergoes a transient recovery. The polarity reversal data are well modeled by a reaction scheme in which the junctional channel has two gates, each with opposite voltage sensitivity, and in which an open gate may close only if the gate in series with it is open. A simple explanation for this contingent gating is a mechanism in which each gate senses only the local voltage drop within the channel. PMID- 6259277 TI - Action of colchicine on membrane currents and synaptic transmission in Aplysia ganglion cells. AB - The action of colchicine, a drug known to disrupt microtubules, on synaptic transmission and voltage-dependent phenomena was studied. Colchicine depressed transmission in both cholinergic and noncholinergic Aplysia ganglionic synapses. In some synapses, this effect was partly due to the curare like properties of the alkaloid. CA2+ currents, analyzed by voltage clamp techniques, were rapidly depressed by intracellular injection of colchicine and more slowly depressed by external application. Injected colchicine acted at much lower concentrations than required extracellularly. The implication of the reduced calcium influx in synaptic transmission is discussed. Colchicine caused a shift in the reversal potential of acetylcholine-activated chloride channels in a direction consistent with an increased intracellular chloride activity. It was concluded that the wide range of actions of colchicine on membrane properties should be taken into account when this drug is used in biological research. PMID- 6259278 TI - Interneuronal control of postural motorneurons in the lobster abdomen. PMID- 6259279 TI - Apparent co-sequestration of immunoreactive corticotropin, alpha-melanotropin, and gamma-lipotropin in hypothalamic granules. PMID- 6259281 TI - Ontogeny of histaminergic neurotransmission in the rat brain: concomitant development of neuronal histamine, H-1 receptors, and H-1 receptor-mediated stimulation of phospholipid turnover. AB - The ontogeny of histaminergic neurotransmission in the rat brain was studied by assessing development of histamine levels in brain regions, along with H-1 receptor binding of [3H]mepyramine and H-1 receptor-mediated cellular events. In the hypothalamus, which is rich in histaminergic innervation, levels of the amine were low at birth, increased sharply at 8 days of age, and reached adult concentrations shortly thereafter; this pattern is typical of most neurotransmitters. In contrast, regions poor in neuronal histamine showed an initially high histamine level and a subsequent decline with development, as is known to occur during general growth of tissues. The developmental profile of H-1 receptor binding sites resembled that of the neuronal histamine pool, and the increases with age resulted from changes in the number of binding sites without alterations in Kd. Cellular responses to H-1 receptor activation were assessed by determining the stimulation of phospholipid turnover evoked by intracisternally administered histamine, a process that has been shown to involve only the neuronal compartment. Again, the developmental profile was superimposable upon that of H-1 receptor binding and that of hypothalamic histamine levels. These studies indicate that ontogeny of histaminergic neurotransmission is a coordinated process, with simultaneous development of neuronal histamine, its key biosynthetic enzyme, and H-1 receptors coupled directly to cellular events. PMID- 6259280 TI - Competitive inhibition of gamma-aminobutyric acid receptor binding by N-2 hydroxyethylpiperazine-N'-2-e-ethanesulfonic acid and related buffers. AB - Several Good buffers (MOPS, ACES, BES, HEPES, ADA, and PIPES) competitively inhibited both high-affinity and low-affinity [3H]gamma-aminobutyric acid receptor binding to rat brain synaptic membranes. The most potent inhibitor was MOPS, which had Ki values of 180 nM and 79 nM for the high- and low-affinity binding sites, respectively. HEPES had Ki values of 2.25 mM and 115 microM. The buffers had no appreciable effect on sodium-dependent GABA binding or on gamma aminobutyrate aminotransferase activity. Surprisingly, the buffers were extremely ineffectual as inhibitors of either high- or low-affinity [3H]muscimol binding. Indeed, they were of the order of 10(5) times less effective in this case than against [3H]GABA binding. These results clearly show (a) that the use of such buffers as MOPS or HEPES should be avoided in studying the interaction of GABA with its receptor, and (b) the binding sites of [3H]GABA and [3H]muscimol are not identical. PMID- 6259282 TI - Uridine metabolism in the goldfish retina during optic nerve regeneration: cell free preparations. AB - The activities of uridine kinase (EC 2.7.1.48), uridine monophosphate (UMP) kinase (EC 2.7.1.3.14), and uridine diphosphate (UDP) kinase (EC 2.7.4.6) were measured in retinal high-speed supernatant fractions following unilateral optic nerve crush in the goldfish. The enzyme activities followed a similar time course, with initial increases 2-3 days following nerve crush, peak activity at 4 days, and a gradual return to basal levels by day 21. The magnitude of the stimulation on day 4 was about 35% in each case. Activities of two enzymes of intermediary metabolism, pyruvate kinase (EC 2.7.1.40) and lactic dehydrogenase (EC 1.1.1.27), were not altered, indicating that the coordinate increases in nucleoside and nucleotide kinase activities were specific responses to the nerve injury. The increased labeling could not be explained by altered phosphohydrolytic activities. The nature of the enhancement was further studied in UDP kinase, the most active of the kinases examined. Neither low-molecular weight components nor substrate availability could account for the observed increase in UDP kinase in the 4 day post-crush retinas. The Km for UDP was unaltered, and a mixing experiment did not support the possibility that stimulatory or inhibitory factors played a role. The enhancement of UDP kinase activity was blocked by injection of actinomycin D following nerve crush. The results suggest that the observed increases in enzymes of uridine metabolism result from their increased formation following nerve crush. PMID- 6259283 TI - Lectin-induced inhibition of nerve growth factor binding by receptors of sympathetic ganglia. AB - Nerve growth factor (NGF) initiates a pleiotypic response in numerous tissues derived from the neural crest by binding to specific plasma membrane receptors. In sympathetic ganglia this receptor has been characterized as a highly asymmetric, minimally hydrophobic, intrinsic membrane protein with a molecular weight of 135,000 (Costrini et al., 1979b). To further characterize this moiety we assessed the effects of lectins on 125I-NGF specific binding to preparations of particulate and nonionic detergent-extracted microsomal receptors of rabbit superior cervical ganglia (SCG). Concanavalin A (Con A) and wheat germ agglutinin (WGA), but not soybean agglutinin or Ulex europaeus 1, induced a concentration related, carbohydrate-specific decrease in 125I-NGF binding. Following Con A exposure, 125I-NGF specific decrease in 125I-NGF binding. Following Con A exposure, 125I-NGF specific binding to particulate SCG receptors was maximally reduced to 23% of control values. WGA similarly reduced NGF binding to particulate microsomal receptors to 37% of control values. Scatchard analysis of growth factor binding following Con A exposure indicated that this lectin effect was principally due to a sixfold reduction in maximum receptor affinity. Lectin associated impairment of NGF binding was also demonstrated by using a Triton X 100 solubilized receptor preparation. These results provide evidence that the high-affinity-state NGF receptor of SCG is a glycoprotein containing N acetylglucosamine and alpha-D-mannopyranoside residues. These residues are probably located in close proximity to the growth factor binding region of the NGF receptor. PMID- 6259285 TI - Distribution of cyclic nucleotide phosphodiesterase in mouse brain. AB - Seventy-one regions of mouse brain, and many subdivisions of some of these, were analyzed for cyclic nucleotide phosphodiesterase. The samples were dissected from lyophilized frozen sections. Since the average sample weighed only 25 ng (20 X 75 X 75 mu3), regions as small as the locus ceruleus could be analyzed. Activities in gray areas ranged 40-fold from a high in the pars reticulata of the substantia nigra to a low in the deep cerebellar nuclei. The activity in fiber tracts also varied about 40-fold, and on a lipid-free dry weight basis was similar to the activity in the gray matter where the fibers originated. The rank order for gray regions was basal ganglia, amygdala, hippocampus, cerebral cortex, most of the diencephalic nuclei, nuclei of the pons, cerebellum, and nuclei of the medulla. PMID- 6259284 TI - Ion channels and membrane potential in stimulus-secretion coupling in adrenal medulla cells. AB - The role of Na+ channels and membrane potential in stimulus secretion coupling in adrenal medulla cell cultures was investigated. Veratridine, aconitine, batrachotoxin (BTX), and scorpion venom, which increase the flux of ions through tetrodotoxin(TTX)-sensitive Na+ channels, all evoke secretion of catecholamines that is blocked by TTX. TTX partially inhibits secretion induced by low concentrations of nicotine in Locke's solution but has no effect on high concentrations of nicotine (20 microM). In Ca2+-sucrose media TTX has no effect on secretion at either high or low concentrations of nicotine. Replacement of Na+ with Li+ in Locke's solution reduces the response to nicotine and to veratridine. Complete replacement of Na+ with hydrazine, diethanolamine, TRIS, and choline completely inhibits the response to nicotine and almost completely inhibits the response to veratridine. Following exposure of cells to 50 mM-100 mM-K+, nicotine does not stimulate catecholamine secretion unless the cells are resuspended in media containing less than 50 mM-K+. Neither dibutyryl-cyclic AMP nor dibutyryl cyclic GMP evokes secretion. alpha-Bungarotoxin (1 microM) did not inhibit nicotine-induced secretion. These studies indicate that Na+ channels and acetylcholine (ACh) receptor ion channels are independently coupled to the influx of Ca2+. The membrane potential appears to affect nicotine- and veratridine evoked secretion. PMID- 6259286 TI - Cyclic AMP generation in medulla oblongata and hypothalamus of hypertension-prone and -resistant rats. AB - Accumulation of cAMP induced by noradrenaline (NA) was higher in the medulla oblongata (MO) of hypertension-prone (H) than in resistant (N) rats, 113 +/- 3 vs. 72 +/- 4 (p less than 0.01). In the hypothalamus (HYP) it was higher in N than in H rats, 148 +/- 8 vs. 92 +/- 6 (p less than 0.01). In both anterior and posterior HYP, the accumulation of cAMP was significantly higher in N than in H rats. cAMP accumulation, in the presence of increasing concentrations of phosphodiesterase inhibitor, showed significant strain differences in both MO and HYP. The observed strain differences in cAMP may be pertinent to the disparate susceptibility to hypertension of H and N rats. PMID- 6259288 TI - Presence of kynurenine hydroxylase in developing rat brain. AB - Kynurenine-3-hydroxylase, an enzyme that is part of the degradative pathway for tryptophan, was present in the cerebral cortex of neonatal rats and exhibited a Km for L-kynurenine close to that of the liver enzyme. This enzyme was enriched in mitochondrial fractions isolated from cerebral cortices of neonatal rats by Ficoll--sucrose gradient centrifugation, with some activity also present in synaptosomal fractions probably due to the mitochondrial content of synaptosomes since cytochrome c oxidase, another mitochondrial enzyme, had a similar distribution in the gradient. Kynurenine hydroxylase as well as monoamine oxidase, another mitochondrial enzyme, had increased specific activities in synaptosomal fractions isolated from 14-day-old rats compared to fractions from 8 day-old rats. Hypothyroidism, induced on the day of birth, resulted in increased activities of kynurenine hydroxylase and monoamine oxidase in synaptosomal fractions isolated from 14-day-old rats. PMID- 6259287 TI - Circadian variation of cyclic AMP in the rat pineal gland. AB - This study was carried out to investigate circadian variation of cyclic AMP contents in the rat pineal glands, using the high-energy microwave radiation technique. The pattern of cyclic AMP concentration in the pineal gland showed a distinct circadian variation, with the maximum level at 0200 and the lowest at 1400. The administration of propranolol completely blocked the dark-induced increase in the pineal cyclic AMP level at 0200, and the administration of isoproterenol induced a threefold, rapid increase in the cyclic AMP level at 1400, although it did not change the level at 0200. PMID- 6259289 TI - In vitro modulation by avermectin B1a of the GABA/benzodiazepine receptor complex of rat cerebellum. AB - Avermectin B1a, a macrocyclic lactone anthelmintic agent, causes a concentration dependent increase of [3H]flunitrazepam binding to membranes from rat cerebellum by increasing the affinity and the number of binding sites. This effect appears to be independent of the concentration of chloride ions. The effects of avermectin B1a occur with high affinity (EC50 = 70 nM), and they persist after washing of the membranes with drug-free buffer. Pretreatment of the membranes with Triton X-100 completely abolishes the action of avermectin B1a. GABA and the GABA-mimetic compounds piperidine-4-sulfonic acid and THIP diminish the effects of avermectin B1a on benzodiazepine receptor binding in a bicuculline-methiodide sensitive mode. In addition, the stimulation of [3H]flunitrazepam binding by avermectin B1a is decreased by the pyrazolopyridines etazolate and cartazolate. These observations suggest that avermectin B1a stimulates benzodiazepine receptor binding by acting on a modulatory site which is independent of the GABA recognition site and of the drug receptor for the pyrazolopyridines, but which is in functional interaction with these sites. PMID- 6259290 TI - Characterization of two [3H]glutamate binding sites in rat hippocampal membranes. AB - The specific binding of L-[3H]glutamate was investigated in the presence and the absence of sodium ions in freshly prepared membranes from rat hippocampus. Sodium ions were found to have a biphasic effect; low concentrations induced a marked inhibition of the binding (in the range 0.5-5.0 mM), whereas higher concentrations resulted in a dose-dependent stimulation of binding (in the range 10-150 mM). These results permit the discrimination of two binding sites in hippocampal membranes. Both Na+-independent and Na+-dependent binding sites were saturable, exhibiting dissociation constants at 30 degrees C of 750 nM and 2.4 microM, respectively, with Hill coefficients not significantly different from unity, and maximal number of sites of 6.5 and 75 pmol/mg protein, respectively. [3H]Glutamate binding to both sites reached equilibrium between 5 and 10 min and was reversible. The relative potencies of a wide range of compounds, with known pharmacological activities, to inhibit [3H]glutamate binding were very different for the Na+-independent and Na+-dependent binding and suggested that the former sites were related to post-synaptic glutamate receptors, whereas the latter were related to high-affinity uptake sites. This conclusion was also supported by the considerable variation in the regional distribution of the Na+-dependent binding site, which paralleled that of the high-affinity glutamate uptake; the Na+ independent binding exhibited less regional variation. PMID- 6259291 TI - Effect of bilirubin on the Arrhenius plots for Na,K-ATPase activities of young and adult rat cerebra. AB - The effect of bilirubin on the temperature dependence of Na,K-ATPase activity was investigated with NaI-treated microsomes prepared from young (13- to 23-day-old) and adult (about 1-year-old) rat cerebra. The Arrhenius plots for the enzymic activities in the young and adult rats showed break temperatures at 26 and 18 degrees C, respectively. In the young rat enzyme, bilirubin caused a shift of the break temperature to 23 and 22 degrees C at concentrations of 60 and 120 microM, respectively, with a significant increase of the activation energy below the break temperature. However, no significant changes in the break temperature and the activation energy were observed in the adult rat enzyme exposed to the same concentrations of the pigment. The results suggest that the lipid environment surrounding the enzyme and modulating its activity in the plasma membranes may differ between the young and adult rat cerebra, and that bilirubin may change the physical state of the lipids related to the activity of the young rat Na,K ATPase. PMID- 6259292 TI - The quaternary structure of chicken acetylcholinesterase and butyrylcholinesterase; effect of collagenase and trypsin. AB - Acetylcholinesterase (EC 3.1.1.7.; AChE) and butyrylcholinesterase (EC 3.1.1.8.; BuChE) from chicken muscle exist as sets of structurally homologous forms with very similar properties. The collagenase sensitivity and aggregation properties of the 'heavy' forms of both enzymes indicate that they possess a collagen-like tail, and their stepwise dissociation by trypsin confirms that they correspond to triple (A12) and double (A8) collagen-tailed tetramers. In addition to this dissociating effect, trypsin digests an important fraction of the catalytic units of AChE, in a progressive manner, removing as much as 30% of the enzyme's mass, without inactivation of the tetramers and of the tailed molecules. The trypsin modified AChE forms closely resemble the corresponding mammalian AChE forms in their hydrodynamic properties. It is not known whether the trypsin-digestible peptides, which do not appear to be involved in the ionic or hydrophobic interactions of the enzymes, are a fragment of the catalytic subunit or whether they constitute distinct polypeptides. PMID- 6259293 TI - Studies on the inhibitory action of opiate compounds in isolated bovine adrenal chromaffin cells: noninvolvement of stereospecific opiate binding sites. AB - In isolated bovine adrenal chromaffin cells, beta-endorphin, dynorphin, and levorphanol caused a dose-dependent inhibition of catecholamine (CA) secretion elicited by acetylcholine (ACh), with an ID50 of 50, 1.3, and 4.3 microM, respectively. The inhibition by the opiate compounds was specific for the release evoked by ACh and nicotinic drugs and was noncompetitive with ACh. Stereospecific binding sites for the opiate agonist [3H]etorphine were found in homogenates of bovine adrenal medulla (KD = 0.59 nM). beta-Endorphin, dynorphin, levorphanol, and naloxone were potent inhibitors of the binding of [3H]etorphine with an ID50 of 12, 0.4, 5.2, and 6.2 nM, respectively. However, [3,5-I2Tyr1]-beta-endorphin, [3,5-I2Tyr1]-dynorphin, and dextrorphan, three opiate compounds with no or little activity in the guinea pig ileum assay, were relatively ineffective in inhibiting the binding of [3H]etorphine (ID50 700, 600, and 10,000 nM, respectively). On the other hand, these three compounds were equipotent with beta-endorphin, dynorphin, and levorphanol, respectively, in inhibiting the ACh-evoked release of CA from the adrenal chromaffin cells (ID50 of 10, 1.5, and 6 microM, respectively). Inhibition of CA release was also obtained with naloxone (ID50 = 14) microM) and naltrexone (ID50 greater than 10(-4) M), two classical antagonists of opiate receptors, and this effect was additive to that of beta-endorphin. These data indicate that the opiate modulation of CA release from adrenal chromaffin cells is not related to the stimulation of the high affinity stereospecific opiate binding sites of the adrenal medulla. The physiological function of these sites remains to be determined. PMID- 6259294 TI - Adenosine and cyclic AMP in rat cerebral cortical slices: effects of adenosine uptake inhibitors and adenosine deaminase inhibitors. AB - The endogenous levels of adenosine functionally linked to cyclic AMP systems in rat cerebral cortical slices are regulated by both adenosine deaminase and adenosine uptake systems. 2'-Deoxycoformycin (2'-DCF), an adenosine deaminase inhibitor, slightly increased basal, adenosine, and norepinephrine-elicited accumulations of cyclic AMP, whereas dipyridamole, an uptake inhibitor, had an even greater effect on cyclic AMP accumulations under the same conditions. Combinations of 2'-DCF and dipyridamole elicited a greater effect than either compound alone. Neither 2'-DCF nor dipyridamole significantly augmented accumulations of cyclic AP elicited by a depolarizing agent, veratridine, suggesting that the adenosine "released" during neuronal depolarization of brain slices is not as subject to inactivation by uptake or deamination as endogenous adenosine in control brain slices. The accumulation of cyclic AMP elicited by a combination of norepinephrine and veratridine was greater than additive. The response to a pure beta-adrenergic agonist, isoproterenol, was not potentiated by 2'-DCF, dipyridamole, or veratridine, consonant with minimal interaction of endogenous adenosine with beta-adrenergic systems. PMID- 6259295 TI - Stimulation of fructose-1,6-biphosphatase activity and synthesis in the cerebral cortex of rats submitted to the convulsant methionine sulfoximine. AB - Purification of rat cerebral cortex fructose-1,6-biphosphatase (FBPase) was performed by substrate elution from phosphocellulose, followed by Sephadex G-200 column filtration. The purified enzyme exhibited an optimum at pH 7.5, and its catalytic properties were very similar to those of the purified whole-brain enzyme previously prepared by Majumder and Eisenberg in 1977. The isolated preparation was electrophoretically homogeneous. The molecular weight of the enzyme subunit was 40,000; the hydrophobic amino acids predominated with 592 residues, and tryptophan was not detected. Expressed as mumol fructose-1,6 biphosphate hydrolysed per g brain tissue wet weight per min, FBPase activity increased twofold 24 h after an intraperitoneal injection of 100 mg per kg body weight of the convulsant methionine sulfoximine (MSO); the increase of the rate of incorporation of [1-14C]valine into brain FBPase was 2.8-fold under the same experimental conditions. A rabbit specific antiserum against rat cerebral cortex FBPase was prepared, and immunotitration studies confirmed both an increase in the number of molecules and the activation of brain FBPase, 24 h after administration of MSO. The increase of the number of brain FBPase molecules, induced by MSO, was due to an increase in synthesis of the enzyme, as shown by a double-label valine incorporation study. PMID- 6259296 TI - Lymphocyte blast transformation responses and viral antibodies in relation to HLA antigens in multiple sclerosis. AB - Fifty four clinically stable multiple sclerosis (MS) patients and 54 age- and sex matched control subjects were HLA-typed, and their responses to herpes simplex, measles, mumps and rubella antigens were examined by the lymphocyte blast transformation test and by serum antibody titrations. Blast transformation response to purified tuberculin (PPD), mitogen phytohaemagglutinin (PHA), pokeweed mitogen (PWN) and concanavalin A (Con A) and spontaneous proliferation of lymphocytes were also studied. MS patients differed from controls by higher antibody levels to measles and rubella viruses and by lower specific blast transformation responses to rubella and measles antigens. When the relative strength of transformation responses was measured, mumps and herpes simplex responses were also lower in MS patients than in controls. In addition, spontaneous lymphocyte proliferation of MS patients in 6-day cultures was lower than that of control lymphocytes. In mitogen stimulations there were no differences between whole groups, but the oldest patients had lower responses to PHA and Con A than their matched controls. The frequency of HLA-Dw2 was 56.6% in MS patients and 32.1% in controls. The patients with and without Dw2 differed from each other only by a lower specific response to PPD in the Dw2-positive group. The immunological response of Dw2-positive controls resembled that of MS patients: low transformation response to viral antigens, low spontaneous proliferation and elevated measles antibodies. This finding supports the function of a genetically determined type of immune responsiveness with low cell-mediated immunity and high levels of certain viral antibodies as one susceptibility factor in multiple sclerosis. PMID- 6259298 TI - Spatial tuning of cells in and around lateral geniculate nucleus of the cat: X and Y relay cells and perigeniculate interneurons. PMID- 6259297 TI - Cytomegalovirus labyrinthitis in an infant: morphological, virological, and immunofluorescent studies. AB - The inner ears obtained from an infant who died of severe congenital cytomegalovirus infection were examined using virological and morphological methods. The techniques of microdissection and surface preparations, immunofluorescent microscopy, and transmission and scanning electron microscopy were employed. Cytomegalovirus was isolated from the perilymph. Injury to the cochlea was minor and was confined to the first half of the basal turn. There were signs of a severe labyrinthitis of the vestibular endolymphatic system. Vestibular organs, especially the saccule and utricle, showed severe damage, with collapse of the saccular membranous wall. Inclusion-bearing cells containing cytomegalovirus antigen, as shown by immunofluorescent staining, and cytomegalovirus virions, as observed by electron microscopy, were found on the endolymphatic surface of the membranous walls, mainly in the saccule and utricle. In the utricle, the infected cells appeared to be concentrated in the regions where the so-called dark cells were located. These dark cells are similar to the proximal tubule cells in the kidney, another common target for cytomegalovirus infection. PMID- 6259299 TI - Afterpotential generation in hippocampal pyramidal cells. PMID- 6259300 TI - High-dose BCNU with autologous bone marrow rescue for recurrent glioblastoma multiforme. AB - Eleven patients with recurrent malignant glioma were treated with single high doses of BCNU ranging from 600 to 1400 mg/sq m. To prevent the characteristic late myelosuppression observed after conventional doses of BCNU, autologous bone marrow harvested just before drug treatment was infused 24 to 36 hours after therapy. Higher doses of BCNU causes earlier and more profound myelosuppression; one patient died on pancytopenia, breakdown of the gut epithelium, and Clostridium septicemia 10 days after receiving 1400 mg/sq m of BCNU. All patients experienced transient emesis; four developed transient elevation of hepatic enzymes, two reversible interstitial pulmonary infiltrates, and two who received 1400 mg/sq m BCNU suffered irreversible cortical damage. Eight patients receiving 600 to 1200 mg/sq m demonstrated reconstitution of polymorphonuclear leukocytes an platelets within at least 30 days after treatment. With a follow-up time of up to 19 months, four patients improved, three stabilized, and three deteriorated and died. The median survival time was 7 months. Computerized tomography performed on patients receiving constant corticosteroids showed diminished contrast enhancement and mass effect in eight patients. High-dose BCNU at doses up to 1200 mg/sq m with marrow rescue is a feasible approach to the treatment of patients with glioblastoma. PMID- 6259302 TI - Herpes encephalitis: a nursing challenge. PMID- 6259301 TI - Pathophysiology of "tethered cord syndrome". AB - The tethered cord syndrome is a clinical entity manifested by progressive motor and sensory changes in the legs, incontinence, back of leg pain, and scoliosis. In order to elucidate the pathophysiology involved in the tethered cord, the reduction/oxidation ratio (redox) was used in vivo of cytochrome alpha,alpha 3 to signal oxidative metabolic functioning in human examples of tethered cord and in animal models. Studies in experimental models indicate marked metabolic and electrophysiological susceptibility to hypoxic stress to lumbosacral cord under traction with greater weights (3, 4 or 5 gm). Similar effects were demonstrated in redox behavior of human tethered cord during surgical procedures. The authors conclude that symptoms and signs of tethered cord are concomitant with lumbosacral neuronal dysfunction which could be due to impairment of mitochondrial oxidative metabolism under constant or intermittent cord stretching. It is assumed that prolonged or accentuated neuronal dysfunction may lead to structural damage to the neuronal perikarya and later of the axons. Untethering procedures in human tethered cord improve oxidative metabolism, and probably facilitate the repair mechanism of injured neurons. PMID- 6259303 TI - Imaging of experimental myocardial infarction with technetium-99m 2,3 dimercaptosuccinic acid. AB - We have studied the use of Tc-99m-labeled 2,3-dimercaptosuccinic acid (Tc-99m DMSA) to scintigraph acute myocardial infarction after coronary occlusion in dogs. Optimal images were obtained 5 hr after injection of radiotracer, with consistent delineation 48 hr after occlusion. Delivery of tracer was dependent on blood flow. Uptake of tracer correlated to extent of infarction as determined by the myocardial depletion of creatine kinase. Myocardial Tc-99m DMSA was protein bound. PMID- 6259304 TI - Nonvisualization of hepatoma with Tc-99m hepatobiliary agent. PMID- 6259305 TI - Tc-99m pyrophosphate myocardial scanning in Chagas' disease. AB - Chagas' disease is a serious protozoan infection affecting up to 20% of populations in some endemic areas. Myocarditis and cardiomyopathy occur in 50% of patients who go on to develop chronic Chagas' disease. We have studied a patient with no overt cardiac symptoms who revealed intense myocardial uptake of Tc-99m pyrophosphate. The significance of this finding in relation to early detection and progress of therapy is explored. PMID- 6259306 TI - Relationships between cholecalciferol metabolism and growth in chicks as modified by age, breed and diet. AB - Fast-growing heavy (White Rock) chicks, fed a vitamin D-deficient diet, exhibited a higher activity of kidney 25-hydroxycholecalciferol-1-hydroxylase (1 hydroxylase) than slow-growing light (White Leghorn x Rhode Island Red) chicks fed the same diet. 1-Hydroxylase and duodenal calcium-binding protein (CaBP) declined with age. Feeding of low energy diets with or without vitamin D resulted in a slower rate of growth and reduced 1-hydroxylase activity and CaBP concentration. Severe dietary restriction of either calcium or phosphorus resulted in a lower growth rate as well as a duodenal CaBP as compared to a moderate mineral restriction. The severe dietary calcium restriction also resulted in a lower 1-hydroxylase activity than that resulting from a moderate restriction. The results clearly indicate that high 1-hydroxylase activity and a high intestinal CaBP are associated with a high growth rate. PMID- 6259307 TI - Plasmacytoid myoepithelioma of the palate. AB - We present the second case of plasmacytoid myoepithelioma of the palate, which was studied by light and electron microscopy. Apart from plasmacytoid cells, some spindle-shaped cells were observed. Both types of neoplastic cells had myoepithelial features, showing abundant 50-80 A thick filaments in the cytoplasm, and exhibited desmosomal junctions. A light cells with less abundant filaments and better equipped with other organelles were observed. Our findings show that there is no clear-cut distinction between the so-called plasmacytoid myoepithelioma and the spindle and stellate myoepithelioma. We suggest that the ultrastructural appearance of these tumors together with the usual histological criteria for malignancy for may be used to evaluate their prognosis. PMID- 6259308 TI - Defective oxidative metabolic responses of neutrophils from stressed neonates. AB - Oxidative metabolic responses of polymorphonuclear leukocytes were assessed in 24 stressed neonates and 22 well, term infants utilizing particulate and soluble stimuli. Stressed neonatal PMNs demonstrated a depressed CL response to zymosan, whereas O2- production for both normal and stressed PMNs of neonates was significantly elevated compared to that in PMNs from adults. These results were not ascribable to phagocytosis since it was comparable in all groups using radiolabeled bacteria. Stressed neonates' PMN responses to soluble stimuli were significantly elevated when compared with those from well neonate and adult controls. Enhanced responses were most prominent in the most severely stressed infants. Treatment of neonates' PMNs with the antioxidants vitamin E and DHB partially corrected the abnormalities, suggesting peroxidative damage to the PMN membrane had occurred. The oxidative metabolic abnormalities of neonates' PMNs are consistent with either a defect in HMPS activity, a defect in functioning of the later portions of the respiratory burst, or a stimulus-specific abnormality in respiratory burst activity. PMID- 6259309 TI - Rotavirus infection and respiratory symptoms. PMID- 6259310 TI - Aniridia-Wilms tumor association. PMID- 6259311 TI - Studies on glucoreceptor. I. Specific binding of D-glucose to partially purified membrane of rat islets of Langerhans. PMID- 6259312 TI - Comparative studies on the hepatotoxic actions of chloroform and related halogenomethanes in normal and phenobarbital-pretreated animals. AB - Hepatotoxic action of CHCl3 was examined biochemically by comparing with those of CCl4 and other related halogenomethanes using normal and phenobarbital (PB) pretreated animals. In the later stage (24 hr), in mice, PB pretreatment augmented CHCl3-induced liver damage as evidenced by an enhancement of elevation of plasma transaminase activities and a parallel rise in liver triglyceride content. In the earlier stage (1 hr), in normal rats, CCl4 (1.0 ml/kg, i.p.) decreased microsomal glucose-6-phosphatase (G-6-Pase) activity and cytochrome P 450 content, whereas no significant effect was observed with the same dose of CHCl3. PB pretreatment produced a significant loss of both enzymes by CHCl3, and enhanced the loss of cytochrome P-450 induced by CCl4, while G-6-Pase activity was little affected by CCl4 in PB-pretreated rats. Both hepatotoxins increased liver malondialdehyde (MDA) content. Some of these early changes in vivo were reproduced in the lipid peroxidation system in vitro. Diethyldithiocarbamate suppressed various toxic manifestations induced by CHCl3 in PB-pretreated rats, but did not protect against the loss of cytochrome P-450 induced by CHCl3 or CCl4. These results suggest that lipid peroxidation hypothesis proposed for CCl4 hepatotoxicity may be applied to the case of CHCl3 though there exist some qualitatively different characteristics between these hepatotoxins, and that the mechanisms of the loss of microsomal G-6-Pase and cytochrome P-450 by either of these hepatotoxins might be different. PMID- 6259313 TI - Negative chronotropic effect of dibutyryl cyclic AMP on the cultured chick embryonic heart cells and the prolongation of the action potential duration. AB - It was shown that there were clear differences between the effects of norepinephrine and dibutyryl cyclic AMP on the cultured chick embryonic heart cells. Norepinephrine and dibutyryl cyclic AMP was applied to the cultured chick embryonic heart cells, and the changes in the beating rate and the action potential configuration were examined. Norepinephrine increased the beating rate, but dibutyryl cyclic AMP produced the significant negative chronotropic effect. Norepinephrine increased the slope of the diastolic depolarization with little affecting the duration of the action potential. In contrast, dibutyryl cyclic AMP significantly prolonged the action potential duration without changing the slope of the diastolic depolarization. Thus, it was shown that dibutyryl cyclic AMP did not always produce the positive chronotropism, and it was suggested that the negative chronotropism on the cultured chick embryonic heart cells was related to the prolongation of the action potential duration. PMID- 6259314 TI - Effect of adenosine and adenosine 5'-monophosphate on cell division of cultured mastocytoma P-815 cells. AB - The growth of mouse mastocytoma P-815 cells in culture (37 degrees, 42 hr) was inhibited by exogenous adenosine (0.2 to 1.0 mM) and more effectively by AMP (0.01 to 0.1 mM), but not by adenine. The inhibited growth (a 25% inhibition by 0.5 mM adenosine and a 80% inhibition by 0.25 mM AMP) was restored to a near control level by the addition of uridine (0.5 mM) to the medium. The pretreatment (37 degrees, 3 hr) of the cells with adenosine or AMP caused a 60% inhibition of incorporation (37 degrees, 2 hr) of [U-14C]aspartate into uracil nucleotides, accumulating 14C-orotate and orotidine. Both dipyridamole, an inhibitor of adenosine uptake, and exogenous adenosine deaminase suppressed the growth inhibition induced by not only adenosine but also AMP. 2-Chloroadenosine, which is resistant to the action of adenosine deaminase, was a more potent growth inhibitor, while 3'AMP and 2'-AMP, which are not hydrolyzed to adenosine by membrane 5'-nucleotidase, were ineffective. Adenosine 5'-sulfate and other 5' substituted adenosines were also ineffective. These observations indicate that AMP inhibits the growth of mastocytoma P-815 cells as a result of its continuous conversion to adenosine and a constant exposure of the cells to a low concentration of adenosine which readily permeates the cell membrane. In addition, adenosine, AMP and their agarose-linked forms rapidly (37 degrees, 20 min) elevated cellular levels of cAMP. This effect was not suppressed by dipyridamole. Apparently adenosine and AMP also act extracellularly for growth inhibition by regulating cAMP levels. PMID- 6259315 TI - Effect of adenosine 3',5'-monophosphate on growth and several functions of cultured mastocytoma P-815 cells. AB - Growth-inhibited mouse mastocytoma P-815 cells at stationary phase contained more histamine, serotonin and adenosine 3',5'-monophosphate (cAMP), and higher activities of histidine decarboxylase and adenylate cyclase than the cells during exponential growth. The elevation of endogenous cAMP levels induced by several growth-inhibiting agents such as N6, O2'-dibutyryl cAMP (Bt2cAMP), prostaglandin E1, AMP and 2-chloroadenosine stimulated several functions characteristic of mastocytoma P-815 cells in culture, elevating the synthesis of histamine and serotonin, the activity of chymotrypsin-like protease, and the incorporation of [35S]sulfate into acidic glycosaminoglycans. 1-Methyl-3-isobutyl-xanthine (MIX), a potent inhibitor of cAMP phosphodiesterase, potentiated stimulatory effect of these agents. The results indicate that cAMP regulates the growth and functions of mastocytoma P-815 cells. [35S]-Sulfated acidic glycosaminoglycans synthesized in cells at stationary phase or in cells treated with Bt2cAMP plus MIX mainly localized in the 3000-10000 x g sedimentable fraction of cell homogenates, and had a molecular weight of 200000 to 400000 based on gel filtration. This acidic glycosaminoglycan was resistant to chondroitinase ABC and the heparin-degrading enzyme present in the 20000 x g sedimentable fraction of the cells, and was identified as a highly sulfated macromolecular heparin based on behaviors on DEAE cellulose column and on acidic electrophoresis. Cycloheximide suppressed the stimulatory effect of Bt2cAMP on the synthesis of histamine and [35S]-sulfated acidic glycosaminoglycan. PMID- 6259316 TI - Changes in the concentration of cyclic nucleotides dependent on their antibodies in plasma. AB - In the process of immunization of rabbits with cyclic AMP or cyclic GMP, the plasma concentration of cyclic AMP or cyclic GMP was markedly elevated as the titer of the antiserum increased. The i.v. injection of anti-cyclic AMP or anti cyclic GMP antiserum into rats or mice also caused a marked increase in the respective cyclic nucleotide in plasma. On the other hand, an injection with the antiserum did not cause any significant increase in urinary cyclic nucleotides. Therefore, the effect of the antiserum seems to be different from that of glucagon or carbamylcholine which increases cyclic AMP or cyclic GMP respectively in both plasma and urine. The injection of the antiserum, but not nephrectomy, caused a significant increase in plasma cyclic nucleotides in adrenalectomized rats. This made it unlikely that the antiserum-induced increase was due to the inhibition of urinary excretion. The plasma cyclic nucleotides, increased by an i.v. injection with the antiserum, servived enzymatic hydrolysis by phosphodiesterase in vitro; most of them proved to be bound to the antibody. It was concluded that the increases in plasma cyclic nucleotides in the process of cyclic nucleotide-immunization were mainly due to decreased metabolic clearance of plasma cyclic nucleotides. PMID- 6259317 TI - Hyperglycemic effect of hydralazine in rats. AB - The effect of hydralazine in the alteration of blood sugar, tissue glycogen and blood cAMP levels in rats were investigated. Hydralazine was found to increase blood sugar level in intact rats when administered i.p. On the other hand, this hyperglycemia was partially blocked either by the treatment of intact rats with propranolol, beta-adrenergic blocker, or by adrenalectomy. Hydralazine treatment increased blood cAMP level, leading to the hyperglycemia, because pretreatment with phentolamine partially blocked the hydralazine-induced hyperglycemia. PMID- 6259318 TI - Effects of ethanol administration and withdrawal on neurotransmitter receptor systems in C57 mice. AB - C57BL/6 mice were treated with 7% (v/v) ethanol in a Bio-Serve liquid diet for 7 days. Some animals were then allowed to withdraw from ethanol for a period of 24 hr. The severity of the ethanol withdrawal was assessed by monitoring behavioral changes and by quantitating the decrease in body temperature that occurred during the first 16 hr of withdrawal. Animals withdrawn from ethanol for 24 hr showed a decreased hypothermic response to apomorphine suggesting that changes in dopaminergic systems had occurred. This possibility was further examined in homogenates of striatum by measuring dopamine-stimulated adenylate cyclase activity and the binding of [3H]spiroperidol. However, there were no changes observed in either basal- or dopamine-stimulated adenylate cyclase activity or in the density or affinity or receptors for [3H]spiroperidol. The affinity of apomorphine for the dopamine receptor was also unchanged. In other experiments, alpha and beta adrenergic receptor-mediated increases in cyclic AMP accumulation were assessed in slices of cerebral cortex. There was no change in cyclic AMP accumulation due to either alpha or beta adrenergic receptors. There was, however, a significant decrease in the density of beta adrenergic receptors in both the ethanol-treated mice and in the withdrawn mice. This decrease was restricted to the beta-2 receptor subtype with no change being observed in the density of beta-1 adrenergic receptors. Ethanol administration was also associated with a significant increase in the density of muscarinic cholinergic receptors in the hippocampus and cerebral cortex. The effect was not observed in animals allowed to withdraw for 24 hr. PMID- 6259319 TI - Receptor interactions of imidazolines. V. clonidine differentiates postsynaptic alpha adrenergic receptor subtypes in tissues from the rat. AB - The alpha-adrenergic effects of clonidine were studied in five tissues of the rat. Postsynaptic alpha adrenergic receptors in these tissues may be divided into three distinct classes based on affinity of the receptors for clonidine. High affinity receptors are located in the aorta and low affinity receptors in the vas deferens. Receptors with intermediate affinity are found in the portal vein, spleen and bladder. The bladder may also contain, to a small extent, a population of receptors similar to those found in the vas deferens which may mediate a different response. Available data suggest that the alpha adrenergic receptor of the rat aorta with high affinity for clonidine may be of the alpha-2 type but located postsynaptically in this tissue. PMID- 6259320 TI - Interaction of the tricyclic antidepressant amitriptyline with prejunctional alpha and muscarinic receptors in the dog saphenous vein. AB - Amitriptyline can cause tachycardia and arrhythmia associated with an excessive release of cardiac catecholamines. We have investigated its effects on norepinephrine release from adrenergic nerves by using the dog saphenous vein as a model of the sympathetic neuroeffector junction. Isolated strips of vein were mounted for isometric tension recording or incubated with [3H]norepinephrine and mounted for superfusion, tension recording and the superfusate. Amitriptyline (10(-6); 5 x 10(-6) M) increased the overflow of [3H]norepinephrine but decreased that of [3,4-3H]dihydroxyphenylglycol from electrically stimulated strips. The selective decreased in the overflow of this metabolite indicates that amitriptyline inhibits neuronal uptake. However, the increased overflow of [3H]norepinephrine caused by amitriptyline also occurred when neuronal uptake was blocked by cocaine (3 x 10(-5) M) but was abolished when prejunctional alpha receptors were blockade by phentolamine (10(-5) M). Amitriptyline attenuated the prejunctional inhibitory action of exogenous norepinephrine, this indicates that the drug interacts with prejunctional alpha receptors. Amitriptyline also antagonized the prejunctional inhibitory action of acetylcholine, both in the absence and presence of cocaine and phentolamine. These effects were not due to a nonspecific action of the drug as it did not reduce the prejunctional inhibitory effect of histamine. Thus, amitriptyline can increase the concentration of norepinephrine at the neuroeffector junction by blockade of neuronal uptake and by interacting with prejunctional alpha and muscarinic receptors. Since the cardiac adrenergic nerves also possess these receptors, the results could help to explain the cardiotoxic effects of the drug. PMID- 6259321 TI - Effect of morphine exposure on mouse liver triglyceride formation. PMID- 6259322 TI - Effect of N-[(S)-1-carboxy-3-phenylpropyl]-L-Ala-L-Pro and its ethyl ester (MK 421) on angiotensin converting enzyme in vitro and angiotensin I pressor responses in vivo. AB - The parent diacid (N-[(S)-1-carboxy-3-phenylpropyl]-L-Ala-L-Pro of MK-421 inhibited hog plasma angiotensin converting enzyme (ACE) by 50% (I50) at a concentration of 1.2 nM and was 17 times more potent than captopril. In vitro the I50 for MK-421, an ethyl ester, was 1200 nM because de-esterification did not occur. Similarly in the guinea-pig ileum, the diacid inhibitor and MK-421 potentiated the contractile effects of bradykinin at an AC50 of 77 pM and 18 nM, respectively. Inhibition of the pressor effects of angiotensin I by the diacid ACE inhibitor occurred at an ID50 of 8.2 micrograms/kg i.v. in rats and 6.4 micrograms/kg i.v. in dogs. Thus, the diacid was approximately 12 times more potent than captopril. The ID50 for MK-421 was 14 and 278 micrograms/kg i.v. in rats and dogs, respectively, because of differences in the rates of de esterification. Oral ACE inhibitory activity was determined by blockade of the pressor effects of angiotensin I in conscious rats and dogs. In rats, but not in dogs, the diacid inhibitor was poorly absorbed, whereas MK-421 was well absorbed in both species. MK-421 inhibited the pressor effects of angiotensin I at 0.1 to 3.0 mg/kg p.o. for at least 6 hr in rats and dogs, and compared to captopril was 8.6 times more potent in rats and 4.6 times more potent in dogs. These data demonstrate that MK-421 and its parent diacid are potent, long-lasting orally active inhibitors of ACE. In addition, the low activity of MK-421 in vitro contrasts with its substantial in vivo activity, and supports the hypothesis that MK-421 is a prodrug that first must be de-esterified to permit full expression of its significant in vivo pharmacological activity. PMID- 6259323 TI - Antihypertensive activity of N-[(S)-1-(ethoxycarbonyl)-3-phenylpropyl]-L-Ala-L Pro (MK-421), an orally active converting enzyme inhibitor. PMID- 6259324 TI - Presynaptic modulation of the release of dopamine from the rabbit caudate nucleus: differences between electrical stimulation, amphetamine and tyramine. PMID- 6259325 TI - Analysis of the cerebrovascular effects of 5-hydroxytryptamine in unanesthetized goats. AB - The effects of 5-hydroxytryptamine (5-HT, serotonin) on cerebral blood flow were evaluated in unanesthetized goats under normal conditions and after selective blockade of 5-HT receptors or impairment of the sympathetic activity present in cerebral vessels. Small doses of 5-HT (0.1-9 micrograms) injected directly into the internal maxillary artery produced dose-dependent reductions in cerebral blood flow, a decrease of 49.8 +/- 2.5% (S.E.M.) occurring with the highest dose. Slow i.v. infusion of lysergic acid diethylamide (0.2-0.4 micrograms/kg/min), methysergide or cyproheptadine (2-5 micrograms/kg/min) partially abolished the cerebral vasoconstriction produced by 5-HT. Both phentolamine and reserpine also diminished the vasoconstriction induced by 5-HT. Goats in which the superior cervical sympathetic ganglion had been removed 7 to 20 days before the experiment showed a significant decrease in the cerebral vasoconstriction elicited by 5-HT. These results indicate that 5-HT produces marked reduction in cerebral blood flow by direct excitatory effect on tryptaminergic receptors together with an indirect effect mediated by the uptake of 5-HT into the sympathetic nerve endings and the release of norepinephrine. PMID- 6259326 TI - Pharmacological characterization of the epsilon-opiate receptor. AB - The epsilon-opiate receptor of the electrically stimulated rat vas deferens has been characterized by means of beta-endorphin, its fragments and derivatives thereof, as well as by its tolerance development. The data provide evidence for the uniqueness of the epsilon-receptor as compared to mu- and delta-receptors of the guinea-pig ileum and the mouse vas deferens, respectively. It appears that an activation of the epsilon-receptor requires at least the beta-endorphin sequence 1-21, which sharply contrasts with the relatively high sensitivity of mu- and delta-receptors to much shorter fragments of this opioid peptide. Furthermore, after chronic exposure of rats to etorphine, the isolated vas deferens shows a dramatic loss of sensitivity to mu-receptor agonists, but only a moderate decrease in sensitivity to beta-endorphin. The presented data contribute to the characterization of a distinct novel type of opiate receptor, the epsilon receptor. PMID- 6259327 TI - Growth hormone stimulation of lipolysis and cyclic AMP levels in perifused fat cells. AB - A rapid, sustained lipolytic response to growth hormone (GH; 20 microgram/ml) was observed in experiments using the perifused fat cell system. No lipolytic response to this agent was observed when fat cells were incubated by the traditional flask incubation method, although isoproterenol stimulated lipolysis in this preparation. In experiments using flask incubated fat cells, isoproterenol increased cyclic AMP content while GH had no effect. However, in the presence of theophylline, isoproterenol and GH significantly increased cyclic AMP levels. In perifused fat cells, both isoproterenol and GH significantly increased cyclic AMP levels in the absence of theophylline. The presence of adenosine deaminase resulted in significant increases in the lipolytic response to isoproterenol and unmasked a lipolytic response to GH when the flask-incubated fat cell system was used. The antilipolytic action of adenosine was determined in perifused fat cells. It was found that the lipolytic response to GH was at least 10 times as sensitive to the inhibitory action of adenosine as was the lipolytic response to isoproterenol. It is concluded that the lipolytic response to GH in the flask-incubation method is prevented by the accumulation of adenosine. This rapid lipolytic response is unmasked in the perifused fat cell system because adenosine fails to accumulate as it is washed from the cell population by the constantly flowing buffer. PMID- 6259328 TI - Relaxation of vascular smooth muscle by isoproterenol, dibutyryl-cyclic AMP and theophylline. AB - There is evidence that the relaxation of vascular smooth muscle produced by isoproterenol or cyclic AMP is mediated by membrane hyperpolarization. The current study investigates the possibility that this hyperpolarization, and hence the relaxation, may be produced by activation of the electrogenic sodium pump. Rat and pig tail artery strips were placed in a 1.0-mM potassium solution for 15 min. This procedure results in a decrease in the activity of the sodium pump. The strips were then made to contract in response to norepinephrine. Two minutes later, the concentration of potassium was increased to 6.0 mM and a relaxation occurred. The amplitude of this relaxation reflects the activity of the sodium pump. Either isoproterenol or dibutyryl-cyclic AMP causes an enhancement (time or degree) of potassium-induced relaxation. Theophylline potentiated potassium induced relaxation in pig arteries but not in rat arteries. The relaxant action of isoproterenol on 1.0 mM barium contractures of rat arteries was inhibited by treatment with ouabain or with potassium-free solution. Ouabain inhibited the relaxant action of isoproterenol in pig arteries contracted with depolarizing potassium solution but not in rat tail arteries. Dibutyryl-cyclic AMP, theophylline and nitroprusside caused relaxation of serotonin-induced contractions; however, in rat arteries these responses were not inhibited by ouabain or by the absence of potassium. Similar studies on tail arteries from baboons, dogs, pigs and cats showed that relaxation by dibutyryl-cyclic AMP or by theophylline had some dependency on the activity of the sodium pump. These observations are consistent with the following conclusions: 1) isoproterenol and cyclic AMP potentiate the electrogenic pumping of sodium and potassium responsible for potassium-induced relaxation; 2) the relaxing action of isoproterenol, dibutyryl-cyclic AMP and theophylline are dependent upon experimental conditions and the species from which the vascular tissue is obtained; and 3) there is a component of isoproterenol- and cyclic AMP-induced relaxation which is not altered by inhibition of the electrogenic sodium pump in the rat. PMID- 6259329 TI - Postsynaptic inhibition of neuromuscular transmission by trifluoperazine. AB - The effect of trifluoperazine (TFP) on neuromuscular transmission was investigated on chick biventer cervicis and frog cutaneous pectoris and sartorius nerve-muscles. In the chick, TFP inhibited indirectly elicited twitches in a frequency-dependent manner. Inhibition was much more rapid at higher frequencies of stimulation. Directly elicited twitches, KCl contracture and action potentials of desheathed frog sciatic nerve and sartorius muscles were unaffected by TFP, suggesting an action of TFP on neuromuscular transmission. TFP depressed end plate potential amplitude and miniature end plate potential (MEPP) amplitude without affecting MEPP frequency. When MEPP frequency was increased by high Na+ Ringer, depression of MEPP amplitude was much more rapid. Similarly, at high frequencies of stimulation (100 Hz), TFP rapidly depressed end plate currents. TFP inhibited contractures induced by bath-applied acetylcholine (ACh); depressed ACh potentials produced by iontophoretically applied ACh; decreased ionic current and time constant of decay of end-plate currents of transected muscle; and inhibited [alpha-125I]bungarotoxin binding to ACh receptor. These data suggest that TFP acts postsynaptically in a frequency-dependent manner to inhibit neuromuscular transmission. Based on recent evidence that TFP is a potent antagonist of calmodulin and that calmodulin is localized mainly to postsynaptic regions, we postulate that the postsynaptic inhibitory actions of TFP may be mediated through antagonism of calmodulin, which in turn may regulate ACh receptor function. PMID- 6259330 TI - Excess magnesium converts red cell (sodium+potassium) ATPase to the potassium phosphatase. AB - 1. The ATPase and phosphatase activities of red cell membranes were measured simultaneously as a function of the magnesium content of the medium. 2. It was found that when the magnesium concentration was greater than that of ATP, magnesium inhibited the ATPase and simultaneously stimulated the phosphatase. The concentrations of magnesium needed for half-maximal stimulation of the phosphatase and half-maximal inhibition of the ATPase were similar. 3. It is suggested that increasing the concentration of magnesium directly causes a change in the conformation of the enzyme from one which favours ATPase activity to one which favours phosphatase activity. PMID- 6259331 TI - The conductance of sodium channels under conditions of reduced current at the node of Ranvier. AB - 1. The single sodium channel conductance gamma and the number of channels N were estimated from fluctuation analysis in voltage-clamped nodes of Ranvier under conditions that decreased the size of the sodium current. 2. Reduction of the sodium current by depolarizing prepulses had no effect on gamma, and, in cases where it could be determined, had no significant effect on N. Partial block of the sodium conductance with tetrodotoxin and saxitoxin also did not affect gamma significantly, but reduced N. 3. gamma was reduced to about 40% of the control value at -5 mV when the pH of the external solution was reduced to 5.0. The pH dependence of gamma is consistent with the theories of Woodhull and of Drouin & Neumcke. 4. The differing effects of prepulses, toxins and pH are interpreted in view of the different time scales of channel inactivation or block under these conditions. 5. The nearly unchanged gamma with prepulses and partial toxin block provides further evidence for the absence of interactions among sodium channels. PMID- 6259332 TI - Does activation of cyclic AMP dependent phosphorylation induced by beta adrenergic agent control the tone of vascular muscle? AB - 1. The relaxing action of the beta-adrenergic agent, isoprenaline, on the porcine coronary artery was investigated in relation to the cyclic AMP level, the endogenous binding of cyclic AMP to the regulatory unit of cyclic AMP dependent protein kinase or the phosphorylation as a result of activation of protein kinase of the muscle homogenate in Krebs solution and excess [K]o solution. These relations were also compared with those of the rat cardiac muscle, in which isoprenaline showed a positive inotropic action. 2. Excess [K]o decreased the cyclic AMP level in proportion to the amplitude of K-induced contracture in the porcine coronary artery. Isoprenaline increased the cyclic AMP level in Krebs solution, while it had no effect in excess [K]o. 3. In the porcine coronary artery, the particulate fraction possessed only 5% of the total cyclic AMP dependent protein kinase, while in the rat cardiac muscle, the particulate fraction was 25% of the total protein kinase. 4. The cyclic AMP dependent protein kinase in the particulate fraction of the porcine coronary artery was already saturated with the endogenous cyclic AMP. However, the binding of cyclic AMP to the protein kinase in the particulate fraction in the cardiac muscle and in the cytosol fraction of both tissues were increased in accordance with the cyclic AMP level. In the coronary artery, the protein kinase in the cytosol fraction was bound to a greater extent with cyclic AMP than was measured in the rat cardiac muscle. 5. In the rat cardiac muscle, isoprenaline enhanced the phosphorylation, detected by autoradiography of SDS gel electrophoresis in individual fractions of phosphorylated protein, while little enhancement was observed in the porcine coronary artery. 6. These observations led to the conclusion that in the porcine coronary artery, beta-adrenergic agent increases the levels of cyclic AMP but does not increase the phosphorylation. If the phosphorylation catalysed by cyclic AMP dependent protein kinase was utilized for Ca mobilization in the cell, the change in the cyclic AMP level would probably not have a causal relation to the muscle tone. This conclusion, however, may not be applicable in the case of the cardiac muscle. PMID- 6259333 TI - Does glial uptake affect GABA responses? AN intracellular study on rat dorsal root ganglion neurones in vitro. AB - 1. Using single barrel pipettes, intracellular records were obtained from surface neurones of isolated rat dorsal root ganglia (DRG) impaled under microscopic vision.2. Responses to gamma-aminobutyric acid (GABA) were elicited either by ionophoresis or by placing drops of concentrated GABA solutions directly into the flow of superfusing Ringer. Using this latter method it was estimated that the GABA concentration eliciting threshold ( approximately 1 mV) responses was 3-20 muM.3. Short (/=0.0005% of the total cellular RNA). Tumors which contained detectable viral transcripts exhibited only low levels of MMTV RNA, which did not appear to represent the accumulation of RNA sequences homologous to the entire MMTV genome; synthesis of MMTV structural proteins was detected in only one tumor. Viral RNA-positive tumors were generally associated with a longer latent period. MMTV RNA expression occurred in tumors classified histologically as adenoacanthomas, as well as in mammary adenocarcinomas, although the cell types in the adenoacanthomas expressing viral RNA were not identified. It does not appear that expression of the endogenous MMTV genome is required for maintenance of all mammary tumors in BALB/c mice, although partial genome expression undetectable by the methods employed cannot be ruled out. Linear regression analyses were performed. The mean time to tumor appearance and the percentage of tumors which were MMTV RNA positive were found to vary linearly as a function of the total dose of 7,12 dimethylbenz[alpha]anthracene administered. The percentage of tumors which were MMTV RNA positive was also shown to be linearly related to the mean time to tumor appearance. These relationships provide a basis for predictions in the BALB/c system related to these parameters. PMID- 6264131 TI - Phosphorylation of acyclovir [9-(2-hydroxyethoxymethyl)guanine] in Epstein-Barr virus-infected lymphoblastoid cell lines. AB - The extent of phosphorylation of 9-(2-hydroxyethoxymethyl)guanine (acyclovir [ACV]) in fresh peripheral leukocytes, in Epstein-Barr virus (EBV)-infected lymphoblastoid cell lines, and in herpes simplex virus type 1-infected lymphoblastoid (P3HR-1) and monkey kidney (Vero) cells was determined by high pressure liquid chromatography, Mono-, di-, and triphosphorylated derivatives of [8-14C]ACV were detected at low levels at various times after superinfection of Raji cells with EBV. The extent of phosphorylation appeared to be related to the concentration of ACV in the medium. Small amounts of ACV mono-, di-, and triphosphates were formed in fresh peripheral leukocyte preparations from EBV- seropositive and -seronegative donors. Comparable ACV monophosphate levels were detected in EBV-negative BJAB and the EBV-positive BJAB/GC cell lines; however, no di- or triphosphate derivatives were detected. Comparable ACV-monophosphate levels were detected in both P3HR-1 and HSV-infected P3HR-1 cell lines; however, larger amounts of ACV di- and triphosphorylated derivatives were detected in the HSV-infected P3HR-1 cells. ACV was converted to the triphosphate to a greater extent in HSV-infected Vero cells than in mock-infected Vero cells or in HSV infected P3HR-1 cells. ACV or its phosphorylated derivatives were converted to guanine nucleotides to a greater extent in lymphoblastoid cells than in fibroblasts (Vero). In conclusion, neither the productive replication of EBV nor the presence of latent viral DNA is required for ACV monophosphate formation in B lymphoblastoid cells. ACV triphosphate, however, was detected only in cells infected productively with EBV. PMID- 6264132 TI - Rapid and sensitive quantitative immunoassay for the large simian virus 40 T antigen. AB - A quantitative, enzyme-linked immunoadsorbent assay has been developed for the simian virus 40 large T antigen. When hamster anti-simian virus 40 tumor serum was used, this method permitted specific identification of large T antigen and its analog, the D2 hybrid protein, a molecule with the same C-terminal approximately 600 amino acids as large T antigen. The sensitivity limit of this test was 0.63 ng of protein. The slopes of the regression lines of the enzyme linked immunosorbent assay titrations performed with highly purified D2 or simian virus 40 large T antigen and with crude extracts of simian virus 40-infected monkey and transformed human cells were identical. Thus, the curve generated with a purified protein, such as D2, can serve as a quantitative standard for the measurement of large T antigen in a wide variety of extracts. Furthermore, solutions containing high salt concentrations and buffers containing up to 0.1% Nonidet P-40 did not interfere with the assay, making it applicable to the measurement of large T antigen in a variety of chromatographic fractions. The enzyme-linked immunosorbent assay was three times more sensitive, was significantly faster to perform, and was quantitatively valid over a much broader large-T-antigen concentration range than the complement fixation test. As such, it should be useful in future studies of the structure and function of this protein. PMID- 6264134 TI - Epstein-Barr virus DNA. IX. Variation among viral DNAs from producer and nonproducer infected cells. AB - A comparative analysis of three Epstein-Barr virus DNAs from American patients with infectious mononucleosis (B95-8, Cherry, and Lamont) and four Epstein-Barr virus DNAs from African patients with Burkitt lymphoma (AG876, W91, Raji, and P3HR-1) indicated that the usual format of Epstein-Barr virus DNA includes a variable number of direct repeats of a 0.35 X 10(6)-dalton sequence (TR) at both ends of the DNA, a 9 X 10(6)-dalton sequence of largely unique DNA (Us), a variable number of repeats of a 2 X 10(6)-dalton sequence (IR), and a 89 X 10(6) dalton sequence of largely unique DNA (UL). Within UL there was homology between DNA at 26 X 10(6) to 28 X 10(6) daltons and DNA at 93 X 10(6) to 95 X 10(6) daltons. The relative sequence order (TR, US, IR, UL, TR) did not vary among "standard" Epstein-Barr virus DNA molecules of each isolate. B95-8 DNA had an unusual deletion extending from 91 X 10(6) to 100 X 10(6) daltons, and P3HR-1 DNA had an unusual deletion extending from 23.5 X 10(6) to 26 X 10(6) daltons. There was sufficient variability among the EcoRI and BamHI fragments of the DNAs to identify each isolate specifically. However, we discerned no distinguishing features for the two geographic or pathogenic origins of the seven isolates. Three intracellular DNAs (Raji, Lamont, and Cherry) and one virion DNA (P3HR-1) were heterogenous in molecular organization and had subpopulations of rearranged or defective molecules. Some regions, particularly 59 X 10(6) to 63 X 10(6) daltons and sequences around TR, frequently participated in rearrangements. Restriction endonuclease maps of the standard and rearranged DNAs of the seven isolates are presented. PMID- 6264133 TI - Restriction alleviation by bacteriophages lambda and lambda reverse. AB - Deletion analysis indicated that the phage lambda restriction alleviation gene(s) ral resides between the cIII and N genes. The Ral+ phenotype was expressed only when lambda ral+ carried a modification such that it was resistant to restriction by the host specificity system. Under these conditions, Ral function protected superinfecting unmodified phages from restriction by EcoK or EcoB but not from restriction by EcoP1. Ral-protected phage DNA was not concomitantly K and B modified, but rather received only the modification specified by the system of the restricting host. Possible mechanisms for Ral action are discussed. Of the other lambdoid phages tested, the hybrid phage lambda rev had Ral activity, whereas phi 80vir and one lambda-P22 hybrid did not. The restriction alleviation activity of lambda rev called Lar, may be the same as the activity expressed in sbcA- strains of Escherichia coli, but it was functionally separable from exonuclease VIII activity (the product of the recE gene), which is also expressed in sbcA- strains. PMID- 6264135 TI - Integrated simian virus 40 DNA: nucleotide sequences at cell-virus recombinant junctions. AB - DNA fragments containing the integrated viral DNA present in the simian virus 40 (SV40)-transformed rat cell lines SVRE9 and SVRE17 were cloned in procaryotic vectors, and the DNA sequences linking SV40 and cell DNA were determined. Comparison of the DNA sequences at the SV40-cell junctions in SVRE9 and SVRE17 cells with those of a previously characterized viral insertion from SV14B cells shows that no specific viral or cellular sequences occur at SV40-cell junctions and that the cellular DNA sequences adjacent to integrated SV40 DNA do not display the direct repeat structure characteristic of transposons and retrovirus proviruses. PMID- 6264137 TI - Translational products of Moloney murine sarcoma virus RNA: identification of proteins encoded by the murine sarcoma virus src gene. AB - In vitro translation of virion RNA of Moloney murine sarcoma virus (MSV) strain 124 yielded major products having molecular weights of 63,000 (63K), 43K, 40K, 31K, and 24K daltons. A molecularly cloned subgenomic fragment of Moloney MSV comprised of the cellular insertion (src) region was utilized in hybridization arrest translation as a means of identifying products of the MSV src gene. MSV src DNA specifically inhibited synthesis of the 43K, 40K, 31K, and 24K proteins, implying that each of these proteins was coded within the MSV src gene. The MSV src-specific nature of this family of proteins was further confirmed by partial purification of MSV src-containing RNAs from MSV non-producer cells. In vitro translation of enriched cellular RNAs yielded products with molecular weights identical to those of the 43K family of proteins synthesized from virion RNA. Nucleotide sequence analysis of the MSV transforming region has revealed a long open reading frame which includes five methionine codons (Reddy et al., Proc. Natl. Acad. Sci. U.S.A. 77:5234-5238, 1980). The molecular weights of the four largest proteins that could be synthesized within this open reading frame corresponded closely to the molecular weights of the 43K family of proteins. Partial cyanogen bromide cleavage of each of the three largest proteins resulted in an uncleaved fragment having a molecular weight equal to that of the smallest (24K) protein. These findings provide direct biochemical evidence that the 43K, 40K, 31K, and 24K proteins are related in their carboxy-terminal regions, as well as information concerning the MSV src gene coding sequences from which each protein originates: PMID- 6264136 TI - Sequence arrangement and biological activity of cloned feline leukemia virus proviruses from a virus-productive human cell line. AB - We examined 14 different feline leukemia virus proviruses from the productively infected human cell line RD(FeLV)-2 after cloning in the modified lambda vector Charon 4A. Each isolate was characterized by restriction digestion and Southern blot analysis. The DNA of each isolate was tested for competence to express virus after uptake by sensitive animal cells (transfection). All but one isolate contained an apparently complete provirus, but only four were infectious. Seven isolates (four noninfectious, three infectious) were studied by heteroduplexing followed by electron microscopy or by S1 nuclease treatment and gel electrophoresis. No regions of nonhomology between proviruses were detected by either criterion, and in no case did we observe homology between flanking sequences. Random shearing or removal of flanking sequences by S1 nuclease had no effect on the status of infectivity of the clones. Thus, we were unable to find molecular differences between infectious and noninfectious proviruses. Our data are consistent with either of the following hypotheses: (i) that there is a short host sequence which is essential as a promoter for virus expression; or (ii) that lack of infectivity is due to small mutations within the proviral genome. PMID- 6264139 TI - Structure and functions of the Kirsten murine sarcoma virus genome: molecular cloning of biologically active Kirsten murine sarcoma virus DNA. AB - The unintegrated closed circular form of viral DNA prepared from NIH3T3 cells infected with Kirsten murine sarcoma virus was cloned into bacterial plasmid pBR322. The closed circular DNA, which consisted of two different-sized populations, was enriched from the virus-infected cells, linearized with BamHI, and inserted into pBR322 DNA. Four different recombinant DNAs (clones 2, 4, 6, and 7) were obtained, and a physical map of each was constructed by using various restriction enzymes. Clone 4 DNA had the largest insertion, corresponding to a complete copy of the linear DNA. This suggested that this insertion contained two copies of the 0.55-kilobase pair long terminal redundant sequence. Clone 2 and clone 6 insertion DNAs had deletions of 0.2 and 0.5 kilobase pair, respectively, which mapped near the right end (3' side of viral RNA) of the linear DNA. Clone 7 DNA appeared to have a deletion of a single copy of the large terminal redundant sequence. Transfection of BALB3T3 cells with the clone 4 DNA insertion showed that this DNA had transforming activity. The efficiency of transfection with clone 4 Kirsten murine sarcoma virus DNA was enhanced eightfold by inserting EcoRI-cleaved viral DNA into the EcoRI site of pBR322. The EcoRI-inserted DNA produced foci with single-hit kinetics, suggesting that a single molecule of Kirsten murine sarcoma virus DNA can induce transformation. Results of transfections with EcoRI-inserted Kirsten murine sarcoma virus DNA cleaved with various restriction enzymes suggested that the first 3.3-kilobase pair region at the left end of the linear DNA is important for the initiation of transformation or maintenance of transformation or both. PMID- 6264138 TI - Gene expression of herpes simplex virus. III. Effect of arabinosyladenine on viral polypeptide synthesis. AB - Arabinosyladenine, an established antiherpetic drug, was used to block herpes simplex virus type 1 DNA synthesis quantitatively in infected xeroderma pigmentosum cells. Kinetic analyses of viral polypeptides synthesized in the presence and absence of this drug revealed that there were at least six distinct kinetic classes of polypeptides. These differed in time of appearance after infection, time of maximum rate of synthesis, kinetics of turnoff, and sensitivity to arabinosyladenine. This study showed that arabinosyladenine had the following three main effects on herpes simplex virus type 1 gene expression. (i) The turnon of immediate early and delayed early polypeptides (kinetic classes 1 and 2) was retarded. (ii) The turnoff of early (immediate early and delayed early) polypeptides (classes 1 through 3) was delayed. (iii) The synthesis of late polypeptides (class 4 through 6) was inhibited by arabinosyladenine, with class 6 severely (80 to 90%) inhibited. The kinetic data presented here, along with the findings of other workers on the effects of inhibition of viral DNA synthesis, suggest that viral DNA replication is required for optimum synthesis of late viral polypeptides. PMID- 6264140 TI - Irreversible conversion of the physical state of herpes simplex virus preceding inactivation by thermal or antibody treatment. AB - The buoyant density characteristics of infectious particles of herpes simplex virus types 1 and 2 were studied by centrifugation in sucrose and cesium chloride density gradients with a high resolution and satisfactory infectivity recovery. It was shown that two populations of infectious virions differing in buoyant density coexisted, the difference being slight but definite. The ratio of heavy (H) to light (L) viral particles varied depending upon the solute used, the strains of virus, and the cell origin. Circumstances favoring degradation of viral infectivity tended to increase the H portion. Incubation at 37 degrees C largely converted L to H, and heating at 45 degrees C converted all virions to H without infectivity. The L to H conversion was irreversible, and no populations intermediate between L and H were clearly observed. Inactivation by UV light irradiation did not affect the density pattern. That H was not an artefact due to penetration of solutes, osmotic pressure, viral aggregation, or loss of the envelope was shown experimentally. A difference in the outer shape of particles between negatively stained L and H populations was demonstrated by electron microscopy. Both cell-released and cell-bound herpes simplex virus particles gave essentially the same result with respect to the above characteristics. The effect of limiting dilutions of antiserum was similar to that of mild thermal treatment, in that denser virions increased parallel to a decrease in less dense virions. Sensitization with early immunoglobulin G, composed mainly of complement requiring neutralizing antibody, caused the density transition, and subsequent addition of complement resulted in a further increase in the buoyant density of the sensitized virions. The DNA in virus particles neutralized with immunoglobulin G plus complement remained resistant to DNase treatment. Possible implications of the phenomena are discussed. PMID- 6264142 TI - Analysis of JC virus DNA purified directly from human progressive multifocal leukoencephalopathy brains. AB - Human polyomavirus JC DNA was purified directly from the diseased brain tissue of two patients with progressive multifocal leukoencephalopathy (PML) by a method employing differential salt precipitation (B. Hirt, J. Mol. Biol. 26:365-369, 1967). Each of the viral genomes (JC-NIH-1 and JC-NIH-2) was molecularly cloned intact in Escherichia coli, using pBR322, at their unique EcoRI (0.00 map unit) and BamHI (0.51 map unit) sites. The JC-NIH-1 genome was approximately 50 base pairs larger and the JC-NIH-2 genome was approximately 50 base pairs smaller than the prototype human polyomavirus JC (Mad-1) DNA. Analysis of the restriction endonuclease cleavage fragments of these two DNAs and the human polyomavirus JC (Mad-1) DNA revealed only slight differences which mapped in a region of the genome extending from 0.67 to 0.74 map unit. From previous homology studies, this region of variance corresponds to the noncoding region to the late side of the origin of DNA replication. PMID- 6264141 TI - Transformation of rodent cells by a cloned DNA fragment of herpes simplex virus type 2. AB - Transformation of rodent cells with isolated restriction endonuclease fragments of herpes simplex virus type 2 DNA identified a region of the genome located between map positions 0.58 and 0.62. These sequences were cloned into pBR322, and the recombinant plasmid was used to transform primary rat embryo cells and NIH 3T3 cells. The transformants were selected for their ability to form dense foci on a monolayer or to form colonies in semisolid medium. In contrast to the parental rat or mouse cells, cell lines transformed with the cloned herpes simplex virus type 2 fragment grow to high saturation densities, replicate in medium containing 1% serum, form colonies in dilute methylcellulose, show reduced levels of fibronectin, and are tumorigenic in nude mice and in their syngeneic hosts. Southern blot hybridizations have detected sequences homologous to the viral fragment in high-molecular-weight DNA from the transformed cell lines that are not present in DNA from normal rodents. In all cases, the plasmid DNA was present in less than one copy per cell, and the patterns of viral sequences changed with passage of the cell line in vivo. PMID- 6264143 TI - Encephalomyocarditis viral RNA can be translated under conditions of poliovirus induced translation shutoff in vivo. AB - Superinfection with poliovirus of HeLa cells already infected with encephalomyocarditis (EMC) virus does not inhibit translation of EMC viral mRNA, whereas residual host translation is completely inhibited. This result indicates that the cap recognition factors inactivated by poliovirus are not required for translation of EMC viral mRNA in vivo, in agreement with previous in vitro experiments. This raises the question of why EMC virus has evolved a capindependent translation mechanism. PMID- 6264146 TI - Vesicular stomatitis virus RNA polymerase can read through the boundary between the leader and N genes in vitro. AB - Triphosphorylated in vitro transcripts of vesicular stomatitis virus were selected by mercury-Sepharose chromatography using adenosine-5'-O-(3 thiotriphosphate) as an affinity probe. Numerous RNAs ranging from less than 47 up to several hundred nucleotides in length were detected. Some of these contain the leader RNA covalently linked to transcripts of the N gene. A comparison of the published genomic sequences at the estimated termination sites of several of these RNAs reveals some homology with the sequence present at both the end of the leader and polymerase genes. PMID- 6264145 TI - IS elements in bacteriophage lambda gene cI prevent expression of gene rex. AB - IS5 inserted into gene cI of bacteriophage lambda greatly reduces the synthesis of Rex protein. Two other IS insertions in cI are even more polar, but two amber mutations near the 5' end of cI allow normal expression of Rex. PMID- 6264147 TI - Identification of unintegrated forms of Kirsten murine sarcoma viral DNA and restriction endonuclease cleavage map of linear DNA. AB - We detected unintegrated linear 7.0-kilobase pair DNA and covalently closed circular DNA species in NIH3T3 cells recently infected with Kirsten murine sarcoma virus. Using the linear DNA, we constructed a restriction endonuclease cleavage map and compared it with the map of Harvey murine sarcoma virus. The restriction endonuclease maps of two segments, one 1.2 kilobase pairs (SmaI site) to 3.7 kilobase pairs (HindIII site) from the right end (corresponding to the viral 3' side) and the other 0.5 kilobase pair (SmaI and KpnI sites) to 0.9 kilobase pair (KpnI site) from the left end, were identical in the two virus types. PMID- 6264148 TI - Mechanism of degradation of duplex DNA by the DNase induced by herpes simplex virus. AB - Reaction intermediates formed during the degradation of linear PM2, T5, and lambda DNA by herpes simplex virus (HSV) DNase have been examined by agarose gel electrophoresis. Digestion of T5 DNA by HSV type 2 (HSV-2) DNase in the presence of Mn(2+) (endonuclease only) gave rise to 6 major and 12 minor fragments. Some of the fragments produced correspond to those observed after cleavage of T5 DNA by the single-strand-specific S1 nuclease, indicating that the HSV DNase rapidly cleaves opposite a nick or gap in a duplex DNA molecule. In contrast, HSV DNase did not produce distinct fragments upon digestion of linear PM2 or lambda DNA, which do not contain nicks. In the presence of Mg(2+), when both endonuclease and exonuclease activities of the HSV DNase occur, most of the same distinct fragments from digestion of T5 DNA were observed. However, these fragments were then further degraded preferentially from the ends, presumably by the action of the exonuclease activity. Unit-length lambda DNA, EcoRI restriction fragments of lambda DNA, and linear PM2 DNA were also degraded from the ends by HSV DNase in the same manner. Previous studies have suggested that the HSV exonuclease degrades in the 3' --> 5' direction. If this is correct, and since only 5' monophosphate nucleosides are produced, then HSV DNase should "activate" DNA for DNA polymerase. However, unlike pancreatic DNase I, neither HSV-1 nor HSV-2 DNase, in the presence of Mg(2+) or Mn(2+), activated calf thymus DNA for HSV DNA polymerase. This suggests that HSV DNase degrades both strands of a linear double stranded DNA molecule from the same end at about the same rate. That is, HSV DNase is apparently capable of degrading DNA strands in the 3' --> 5' direction as well as in the 5' --> 3' direction, yielding progressively smaller double stranded molecules with flush ends. Except with minor differences, HSV-1 and HSV 2 DNases act in a similar manner. PMID- 6264144 TI - Biochemical characterization of cells transformed via transfection by feline sarcoma virus proviral DNA. AB - Murine fibroblasts transformed by transfection with DNA from mink cells infected with the Snyder-Theilen strain of feline sarcoma virus and subgroup B feline leukemia virus were analyzed for the presence of integrated proviral DNA and the expression of feline leukemia virus- and feline sarcoma virus-specific proteins. The transformed murine cells harbored at least one intact feline sarcoma virus provirus, but did not contain feline leukemia virus provirus. The transformed murine cells expressed an 85,000-dalton protein that was precipitated by antisera directed against feline leukemia virus p12, p15, and p30 proteins. No feline oncornavirus-associated cell membrane antigen reactivity was detected on the surfaces of the transformed murine cells by indirect membrane immunofluorescence techniques. The 85,000-dalton feline sarcoma virus-specific protein was also found in feline cells transformed by transfection. However, these cells also contained env gene products. The results of this study demonstrate that the feline sarcoma virus genome is sufficient to transform murine cells and that expression of the 85,000-dalton gag-x protein is associated with transformation of both murine and feline cells transformed by transfection. PMID- 6264149 TI - Association of the transformation-specific protein pp60src with the membrane of an avian sarcoma virus. AB - The transformation-specific protein pp60(src) coded for by avian sarcoma viruses and its associated protein kinase activity is present in virus particles of Rous sarcoma virus, Schmidt-Ruppin strain, subgroup D. Quantitative comparison of the immunoglobulin G-phosphorylating activity in Schmidt-Ruppin D virus and Schmidt Ruppin D virus-transformed fibroblasts indicated that there was two- to fourfold less activity in the virus particles. Disruption of virus particles with nonionic detergent demonstrated that the protein kinase activity fractionated together with the viral membrane protein gp85. Therefore, viral membranes were isolated by floating detergent-disrupted virus through a discontinuous sucrose density gradient. At a characteristic density corresponding to 26% sucrose, viral membranes were identified by the radioactively labeled viral glycoprotein and furthermore by the membrane marker enzyme Na(+)-K(+)-stimulated, Mg(2+)-activated ATPase and were visualized by electron microscopy. Contamination by cell membranes could be ruled out, since (i) the virus preparation was free of cell membrane contaminants as judged from electron microscopy, (ii) floating of intact virus did not release membraneous material, and (iii) virus-free tissue culture fluid from Schmidt-Ruppin D virus-transformed nonproducer cells (which potentially contain cell membranes) did not contribute any immunoglobulin G phosphorylating activity after mixing with nontransforming virus and pelleting it. Both pp60(src) and the protein kinase activity were found to be associated with the viral membrane. Solubilization of virus by detergent released two phosphoproteins, with molecular weights of 42,000 and 45,000 which reacted with sera specific for pp60(src) and revealed protein kinase activity but which were not membrane bound and may have represented degradation products of pp60(src). Surface iodination of intact virus particles (harvested at 3-h intervals) did not result in radioactive labeling of pp60(src), whereas collection at 24-h intervals allowed iodination of pp60(src). In contrast to the viral glycoprotein gp85, the iodinated virion-associated pp60(src) was insensitive to mild proteolytic treatment. Binding to tumorbearing-rabbit serum, immunoglobulin G phosphorylation, and endogenous phosphorylation of 60,000-, 45,000-and 42,000 dalton proteins required lysed virus and were not possible with intact virus. These results indicated that pp60(src) was embedded within the viral membrane. Membrane proteins phosphorylated in vitro were analyzed for their phosphoamino acid composition. Eight polypeptides exhibited phosphorylation in tyrosine and were absent in nontransforming viral controls. PMID- 6264150 TI - Early syncytium formation by bovine leukemia virus. AB - Bovine leukemia virus (BLV) from either persistently infected bat cells or fetal lamb kidney cells induced rapid syncytium formation in F81 indicator cells. Distinct syncytia were seen within 2 h after inoculation of cells with highly concentrated (500-fold) cell-free BLV preparations and within 4 to 8 h when unconcentrated cell-free BLV preparations were used. Indicator cell densities of 1 x 10(5) to 2 x 10(5) were optimal for rapid and maximal syncytium formation. Pretreatment of BLV with reference BLV leukemic serum and antiserum prepared against purified BLV significantly inhibited (95%) syncytium formation. Reference bovine viral diarrhea virus serum, foamy-like bovine syncytial virus serum, and control serum had little effect (17% inhibition). Antiserum to BLV gp51 inhibited syncytium formation by greater than 96%, whereas antiserum to BLV p24 reduced syncytium activity to a much lesser extent (38% inhibition). Treatment of BLV with beta-propiolactone (0.005 to 0.05%) had little or no effect upon syncytium forming activity, whereas UV irradiation (15 ergs/mm(2) per s for 30 min) reduced, but did not completely destroy, the fusion activity. However, both beta propiolactone and UV irradiation drastically reduced the replication potential of BLV, as demonstrated by the lack of p24 expression in the inoculated cells. Concentrations of cycloheximide, cytosine arabinoside, tunicamycin, and 2-deoxy-D glucose which effectively blocked cellular macromolecular synthesis did not significantly inhibit syncytium formation. These latter results suggested that de novo protein and DNA synthesis as well as protein glycosylation were not required for early syncytium formation. Thus, these experiments demonstrated that replication of BLV by the indicator cells was not essential for cell fusion. PMID- 6264153 TI - Efficient production of xenotropic murine leukemia virus unintegrated proviral DNA by cocultivation. AB - Cocultivation of virus-producing cells and homologous uninfected cells yielded greater than a 10-fold increase in linear and superhelical proviral DNAs as compared with previously published techniques. PMID- 6264152 TI - Restriction and modification in Bacillus subtilis: gene coding for a BsuR specific modification methyltransferase in the temperate bacteriophage phi 3T. AB - The resistance of Phi3T DNA to degradation by the restriction enzyme BsuR or its isoschizomer HaeIII is due to obligatory modification of such DNA. Biochemical and genetical experiments indicate that Phi3T codes for a methyltransferase, which methylates Phi3T DNA itself or heterologous DNA at target sites 5'-GG(*)CC. PMID- 6264151 TI - Temperature-sensitive mutants of Fujinami sarcoma virus: tumorigenicity and reversible phosphorylation of the transforming p140 protein. AB - Several clones of Fujinami sarcoma virus (FSV) isolated from a laboratory stock or from mutagenized virus were temperature sensitive (ts) in transformation of cells in culture. When shifted from the permissive (37 degrees C) to the nonpermissive (41.5 degrees C) temperature, the cellular phenotype reverted to normal within 2 h, but it required about 48 h at 37 degrees C to revert back to the transformed morphology. A temperature-resistant (tr) FSV clone was isolated from a tumor of an animal. All ts mutants were tumorigenic in animals but induced tumors only after latent periods of 12 to 25 days, compared to 5 to 6 days with tr virus. The ts lesions of the FSV mutants affected 90% of the phosphorylation of the nonstructural, gag-related 140,000-kilodalton phosphoprotein coded by FSV (p140), but did not affect virus replication or the synthesis of p140. Upon shifting from the permissive to the nonpermissive temperature, p140 was 90% dephosphorylated with an approximate (32)P half-life of 20 min. When shifted back to the permissive temperature, the preexisting p140 was rephosphorylated in the absence of protein synthesis within a 90-min test period. Likewise, most of the phosphate of fully phosphorylated p140 was exchanged at the permissive temperature within 30 to 90 min even when protein synthesis was inhibited. However, the protein structure of p140 had a half-life of 5 h at both temperatures. These results prove p140 to be a substrate of reversible phosphorylation. Superinfection and transformation of ts FSV-infected cells maintained at the nonpermissive temperature with acute leukemia virus MC29 failed to phosphorylate p140. It would follow that in vivo phosphorylation of ts p140 is controlled by an FSV-specific mechanism and is a prerequisite, not a consequence, of transformation. p140 of ts FSV recovered from cells maintained at 41.5 degrees C with anti-gag serum was over 10 times less phosphorylated by associated kinase than the same protein recovered from cells at 37 degrees C if assayed in vitro at 20 degrees C. This kinase activity associated with or dissociated from p140 with a half-life of less than 30 min during temperature shifts of ts FSV-infected cells. However, p140 recovered from ts FSV-infected cells maintained at 37 degrees C was phosphorylated by associated kinase in vitro not only at 20 degrees C but also, and essentially at the same level, at 41.5 degrees C. This suggests that the kinase associated with the immunocomplex of p140 of ts FSV is not temperature sensitive. p140 translated in vitro from ts and tr FSV RNA lacked kinase activity. We conclude that a fully phosphorylated p140 is necessary for the maintenance of transformation by FSV. This is consistent with the notion that other highly oncogenic viruses also code for nonstructural phosphoproteins with probable transforming function. A model which postulates that p140 is a substrate of reversible phosphorylation and that the lesion of the ts FSV clones described herein affects association of p140 with a cellular kinase rather than a hypothetical intrinsic kinase activity of the protein is most compatible with our data. PMID- 6264154 TI - Gene-coding assignments of rotavirus double-stranded RNA segments 10 and 11. AB - The gene-coding assignments for genome segments 10 and 11 of a simian virus and two human rotaviruses were determined. For those viruses having a "long" RNA gel pattern (electropherotype), segments 10 and 11 encoded proteins NS(3) and O(4), respectively. The human virus with a "short" electropherotype had the opposite assignments and also differed in (enzyme-linked immunosorbent assay) serotype from the human virus with a long electropherotype. PMID- 6264155 TI - Polyoma virus minichromosomes: a soluble in vitro replication system. AB - Polyoma virus minichromosomes were isolated from infected 3T6 cells by hypotonic extraction of isolated nuclei. The kinetics of in vitro DNA synthesis in the nuclear extract was similar to that observed with intact nuclei. The majority of the products of in vitro DNA synthesis sedimented with replicative intermediate (RI) minichromosomes and migrated as two bands (RI-a and RI-b) on 1.4% agarose gels. The kinetics of deoxynucleotide monophosphate incorporation into these species was consistent with the existence of several rate-limiting steps in in vitro replication by polyoma minichromosomes. Electron microscope analysis showed that the RI-a band consisted almost entirely of RI theta structures ranging from 46 to 87% replicated, with one-half of all theta structures 67 +/- 4% replicated. The RI-b material was more complex, consisting of sigma and alpha structures with tails ranging from 7 to 114% of polyoma genome length and, less frequently, of linked and multiple linked dimeric structures. PMID- 6264156 TI - Polyoma virus minichromosomes: associated DNA molecules. AB - Electron microscopy was used to identify and quantitate DNA molecules associated with 3H-labeled polyoma minichromosomes which had been fractionated on a sucrose gradient. The percentage of replicating DNA molecules observed in the fractions of the gradient normally designated the replicative intermediate region was up to ninefold higher than in fractions from the mature region. Nevertheless, because of the higher overall concentration of polyoma DNA molecules in the mature region, nearly as many replicating DNA molecules were computed to be in the mature region as in the replicative intermediate region. The replicating molecules in the mature region was predominantly early replicative intermediates. Almost all late replicative intermediates were found in the replicative intermediate region. Under aqueous spreading conditions, a substantial fraction of the replicating DNA structures appeared to be asymmetrical or otherwise unusual, suggesting that extensive single-stranded regions may exist in replicating polyoma minichromosomes. PMID- 6264157 TI - Polyoma virus minichromosomes: associated enzyme activities. AB - Polyoma minichromosomes were isolated and fractionated on glycerol gradients as described by Gourlie et al. (J. Virol. 38:805-814, 1981). Specific assays for DNa polymerases alpha, beta, and gamma, DNA topoisomerase I, and RNase H were carried out on each fraction. The number of units of activity in each fraction was compared with the number of total polyoma and replicative intermediate DNA molecules in each fraction determined by quantitative electron microscopy (M. R. Krauss and R. M. Benbow, J. Virol. 38:815-825, 1981). DNA polymerase alpha cosedimented with polyoma replicative intermediate DNA molecules. DNA polymerase beta and DNA topoisomerase I activities sedimented with mature polyoma minichromosomes. Although the bulk of RNase H activity sedimented in the minichromosome region, the peak of activity was found one fraction behind the peak of mature minichromosomes. Virtually no DNA polymerase gamma activity cosedimented with polyoma minichromosomes. PMID- 6264158 TI - Characterization of polypeptides immunoprecipitable from Pichinde virus-infected BHK-21 cells. AB - Using hamster anti-Pichinde virus serum, we immunoprecipitated polypeptides from BHK-21 cells infected with Pichinde virus. Seven immunoprecipitable polypeptides exhibited a time- and multiplicity of infection-dependent appearance when the cultures were pulse-labeled with L-[35S]methionine for 1 h. The predominant polypeptide was a nucleoprotein (NP) of 64,000 daltons. Components of 48,000, 38,000, and 28,000 daltons, when analyzed by two-dimensional tryptic peptide mapping, were found to be derived from NP. After a 3-h chase period, polypeptides of 17,000, 16,500, and 14,000 daltons were evident, and peptide mapping revealed that these three polypeptides were also related to NP. During a series of pulse chase experiments, a 79,000-dalton glycoprotein (GPC) was cleaved to glycoproteins of 52,000 and 36,000 daltons. Radiolabel in a polypeptide of approximately 200,000 daltons (L) did not chase into smaller cleavage products. L, GPC, and NP were found to be unique by two-dimensional tryptic peptide mapping. Comparison of polypeptides immunoprecipitated from infected cells with structural components of purified virus revealed that L protein was evident in both. This is the first report of a high-molecular-weight polypeptide in Pichinde virus particles and infected cells. PMID- 6264159 TI - Virus-associated RNAs of naturally occurring strains and variants of group C adenoviruses. AB - We compared the sequences of the virus-associated (VA) RNAs of group C adenoviruses, serotypes 1, 2, 5, and 6, and of three variants of adenovirus type 2 (Ad2) selected for loss of the BamHI restriction site in the VA RNAI gene. In the naturally occurring strains. VA RNAI exists in two forms which differ by two nucleotides: one form is found in Ad2 and Ad6, and the other is found in Ad1 and Ad5. There are three sites of variation in Va RNAII, the Ad1, Ad2, and Ad5 forms each differing from Ad6 VA RNAII at one of the positions. One of the selected variants has a four-base duplication within the BamHI cleavage site, whereas the two others have acquired a VA RNAI sequence indistinguishable from that of Ad5. The findings are interpreted in terms of the secondary structures of the VA RNAs and the interrelationships among the viruses. PMID- 6264160 TI - Two forms of VPg on poliovirus RNAs. AB - The protein (VPg) linked to the 5' termini of poliovirus RNAs resolved into two species when subjected to non-equilibrium electrofocusing. The differently charged forms of VPg were not due to protein phosphorylation nor to variability of the number of phosphate residues associated with the nucleotide moiety remaining after RNase digestion of the nucleoprotein. Single-stranded viral RNA isolated from mature virions contained predominantly the more basic form of VPg, whereas unpackaged single-stranded RNa remaining in cells at the end of the virus replication cycle contained predominantly the more acidic form of VPg. Replicative-form (RF) molecules also contained both species of VPg, with the more acidic form representing the major species. Both plus and minus RNA strands in RF had similar VPg compositions; however, there appeared to be a strongly selective loss of VPg from only the minus strand in RF, particularly at late times postinfection. PMID- 6264161 TI - Rearrangement of integrated viral DNA sequences in mouse cells transformed by simian virus 40. AB - The organization of viral DNA sequences in several cell lines derived from a primary colony of simian virus 40 (SV40)-transformed mouse cells was analyzed to examine the origin of the various distinctive patterns of SV40 sequence arrangement present in transformed cells. This analysis revealed a complex arrangement of viral sequences in the uncloned transformed cells but simplified arrangements in cloned derivatives of the primary transformant. The cell lines studied had certain SV40 sequence arrangements in common, but the cloned lines had lost some parental arrangements and acquired new arrangements. These results indicate that the arrangement of viral sequences in some SV40-transformed cells is not fixed but that alterations occur after integration, creating a heterogeneous population of transformants. In the process, expression of viral genes may be altered. Possible causes for and implications of this genetic instability are discussed. PMID- 6264162 TI - Sedimentation characteristics of newly synthesized Epstein-Barr viral DNA in superinfected cells. AB - Replicating Epstein-Barr virus (EBV) DNA molecules isolated from superinfected Raji cells were shown to consist of 80S to 65S and 58S (mature) molecules Pulse chase experiments showed that radioactive label of DNAS molecules with the larger sedimentation coefficients was partially chased into 58S labeled forms. Formation of large concatemers of viral DNA could not be detected at any time after superinfection. The continuous presence of the 65S viral DNA intermediate throughout the replicative cycle combined with the observed inhibition of EBV DNA synthesis by addition of nontoxic levels of ethidium bromide to the superinfected cell culture led us to propose that EBV replication proceeds via a relaxed circular DNA intermediate. PMID- 6264163 TI - Immunological properties of a type C retrovirus isolated from cultured human T lymphoma cells and comparison to other mammalian retroviruses. AB - HTLV strain CR (HTLVCR) is a retrovirus which was isolated from a human T-cell lymphoma cell line. A protein of molecular weight 24,000 p24, was purified from this virus. Several results indicate that this p24 is an internal core protein of HTLVCR. (i) The p24 copurified with viral cores. (ii) It was labeled with 125I after disruption of the virus, but not when undisrupted virus was iodinated. (iii) The amount of p24 was directly proportional to the amount of HTLVCR. (iv) In chromatographic properties, the HTLVCR p24 behaved similarly to the major structural protein (24,000- to 30,000-molecular-weight protein) of other retroviruses. A rabbit antiserum raised against disrupted HTLVCR precipitated the labeled p24, and the precipitation was competed for by unlabeled HTLVCR and by cytoplasmic proteins from cells producing HTLVCR, but not by proteins from normal human cells, including normal growing human T-cells, and several cultured human cutaneous T-cell lymphoma lines. Proteins from several mammalian type B, type C, and type D viruses also failed to compete in this precipitation. Moreover, HTLVCR did not react in homologous and interspecies assays for p30 antigens of several mammalian type C and type D viruses. These observations agree with immunological comparisons between reverse transcriptase of HTLVCR and other retroviruses and nucleic acid sequence homology studies which indicate that the various HTLVCR isolates represent new retroviruses found in some human T-cell neoplasias. PMID- 6264165 TI - Analysis of the myeloproliferative sarcoma virus genome: limited changes in the prototype lead to altered target cell specificity. AB - The myeloproliferative sarcoma virus (MPSV) derived from Moloney sarcoma virus (MSV-Mol) is a unique sarcoma virus which causes expansion of the hematopoietic stem cell compartment as well as the erythroid and myeloid cell lineages. MPSV also induces spleen focus formation in adult mice as do Friend and Rauscher viruses. Analysis of the MPSV genome on methyl mercury gels showed that the genome size is 7.0 kilobases, which is larger than the defective genome of any known MSV-Mol isolate. Hybridization analysis with specific cDNA probes showed that MPSV is a modified sarcoma virus with no sequences in the unique region of the defective sarcoma genome related to unique Friend virus sequences. The only viral sequences in the defective genome other than helper virus-related sequences are derived from the Moloney sarcoma virus genome with no new cellular sequences added. There was no evidence for induction of xenotropic virus sequences in MPSV infected spleens of DBA/2J mice, indicating that spleen focus formation can be obtained by different mechanisms. PMID- 6264166 TI - DNA sequences of polyoma virus early deletion mutants. AB - The DNA sequences of four "early" viable deletion mutants of polyoma virus have been determined. Two of these (dl-8 and dl-23) are mutants with deletions in the region of the genome that codes for parts of both large and middle T-antigens, and two (dl-6 and dl-28) are mutants with deletions around the viral origin of replication. The former mutants have altered transformation properties relative to wild-type virus, and dl-8 appears to be replication deficient (B. E. Griffin and C. Maddock, J. Virol. 31:645-656, 1979). Sequences are discussed in terms of the altered phenotypes observed for the various mutants, the DNA structures and protein sequences that are affected by the deletions, and how these might affect the biological properties of the mutants. PMID- 6264164 TI - Ability of nonpermissive mouse cells to express a simian virus 40 late function(s). AB - Mouse cells are fully nonpermissive for simian virus 40 (SV40). Infection does not lead to detectable virus replication. In this report, it was shown, first, that spliced 16S and 19S SV40 late mRNA were present in cytoplasmic and polysomal polyadenylated acid+ RNA preparations from SV40-infected baby mouse kidney cells. The 16S and 19S SV40 late mRNA's produced in infected baby mouse kidney cells were identical to or similar to the 16S and 19S SV40 late mRNA's produced in permissive monkey cells as judged by their S1 mapping patterns performed with the late strand of HpaII-BamHI fragment B and by their sedimentation patterns in a sucrose gradient. It was also shown that the 16S late mRNA from infected baby mouse kidney cells could be translated into a polypeptide which was identical to or similar to virion protein VP1 in every aspect examined, including the patter of peptide mapping by limited proteolysis. Second, we reported that mouse kidney cells produced detectable, although low, levels of SV40 virion protein VP1, as shown by the sodium dodecyl sulfate-polyacrylamide gel autoradiogram of [35S]methionine-labeled proteins immunoprecipitated by a rabbit antiserum directed against SV40 virion proteins. Third, it was reported that infected baby mouse kidney cells produced late mRNA's either (i) when the infection was done at a restrictive temperature with the nonleaky tsA58 mutant or (ii) in cells treated with 100 microgram of cycloheximide per ml, in which large T antigen synthesis was inhibited by more than 99.9%. This suggested that large T antigen was not required for the synthesis of late mRNA in mouse cells. PMID- 6264168 TI - Powassan virus infection in snowshoe hares (Lepus americanus). AB - Sera from snowshoe hares (Lepus americanus) trapped near Rochester, Alberta, Canada were tested for Powassan virus antibody by the constant virus/serum dilution neutralization test. Of 1264 serum samples tested, 137 had an antibody titer of at least 1:4 for Powassan virus. Ten hares were inoculated with Powassan virus in the laboratory. Viremia lasted 4-5 days and ceased with the appearance of Powassan antibody in the serum. Neutralizing antibody reached a peak titer of 1:119 on day 15 post-inoculation and was still detectable 13 months post inoculation. PMID- 6264169 TI - Mortalities associated with herpesvirus infection in captive macropods. AB - Fatal cases of herpesvirus infection in a quokka (Setonix brachyurus), eight grey dorcopsis wallabies (Dorcopsis muelleri luctuosa) in two separate outbreaks, as well as presumptive fatal herpesvirus infection in a western grey kangaroo (Macropus fuliginosus) are described. All were captive animals and deaths were preceded by a period of stress. Lesions occurred most often in alimentary tract epithelium, respiratory tract, skin, genital epithelium, conjunctivae, liver and adrenal cortex. Herpesviruses were recovered from the quokka and a grey dorcopsis wallaby from each outbreaks. The implications, particularly concerning certain apparently susceptible species, for those responsible for the health of macropod collections are discussed. PMID- 6264170 TI - Procedure for obtaining THC for cancer patients. PMID- 6264172 TI - beta-Endorphin levels lower in arthritis patients. PMID- 6264171 TI - Hyperphagia and obesity. Relationship to medial hypothalamic lesions. AB - Progressive left hemiparesis followed by face and trunk cutaneous vasodilation and hyperphagia developed in a 28-year-old man. He began eating five to six meals a day and gained 16 kg in 60 days. Computed tomography disclosed a neoplastic lesion involving the midline via the hypothalamus and reaching the contralateral lenticular nucleus. Findings from endocrine studies, including thyroid stimulating hormone, growth hormone, prolactin, and cortisol serum levels, were normal. Hyperphagia and consequent obesity were associated with bilateral destruction of the ventromedial hypothalamic area; cutaneous vasodilation was related to involvement of the preoptic area. PMID- 6264167 TI - Effect of sodium butyrate on induction of cellular and viral DNA syntheses in polyoma virus-infected mouse kidney cells. AB - Sodium butyrate inhibited initiation of viral and cellular DNA replication in polyoma virus-infected mouse kidney cells. Ongoing viral or cellular DNA replication, however, was not affected by the presence of the substance. Butyrate had no effect on T-antigen synthesis and on the stimulation of transcription, one of the earliest reactions of the infected cells to the appearance of T-antigen, nor did it inhibit expression of late viral genes (synthesis of viral capsid proteins). In addition to blocking the onset of DNA synthesis, butyrate also inhibited stimulation of the activities of enzymes involved in DNA synthesis. When butyrate was removed, viral and cellular DNA syntheses were induced in parallel after a lag period of approximately 4 h. At the same time, the activities of enzymes involved in DNA synthesis increase. If protein synthesis was inhibited during part of the lag period, the initiation of DNA synthesis was retarded for the same time interval, suggesting that the proteins involved in the initiation of DNA replication had to be made. We have developed an in vitro system for measuring DNA synthesis in crude nuclear preparations which mimics the status of DNA replication in intact cells and may help in future experiments to study the requirements for initiation of cellular and viral DNA synthesis and the possible involvement of T-antigens in this reaction. PMID- 6264173 TI - Emphysematous cystitis due to Clostridium perfringens. PMID- 6264176 TI - Ultrastructural alterations of the myocardium in coxsackie B-3 virus myocarditis in mice. 18 months follow-up study by transmission and analytical electron microscopy. PMID- 6264175 TI - Plasma level of norepinephrine, cyclic AMP and cyclic GMP in essential hypertension. PMID- 6264174 TI - Sympathetic nervous systems in chronic cor pulmonale. AB - Twenty-three patients with chronic respiratory failure and 30 normal subjects were studied to assess the sympathetic nervous activity in chronic hypoxic states, especially in chronic cor pulmonale. Of the 23 patients, 13 had a right ventricular hypertrophy (RVH) pattern on the electrocardiogram. Plasma norepinephrine (NE), dopamine-beta-hydroxylase (DBH), cyclic adenosine 3',5' monophosphate (cyclic AMP) and cyclic guanosine 3',5'-monophosphate (cyclic GMP) concentrations were measured before and after oxygen inhalation. Plasma NE concentrations were 0.57 +/- 0.07 ng/ml in patients with chronic respiratory failure and 0.22 +/- 0.02 ng/ml in controls (p less than 0.001). Moreover, plasma NE concentrations were higher in patients with RVH than without (p less than 0.05), and these concentrations decreased significantly (p less than 0.05) in the former patients after oxygen inhalation. Plasma cyclic AMP concentrations were 31.2 +/- 2.6 pmol/ml in cases of chronic respiratory failure and 17.4 +/- 0.7 pmol/ml in controls (p less than 0.001) with no difference in plasma cyclic GMP and DBH concentrations. These results suggest that a significant proportion of patients with chronic respiratory failure, especially with cor pulmonale, were in hyper-adrenergic states partially due to hypoxia. PMID- 6264177 TI - Experimental coxsackie B-3 virus myocarditis in golden hamsters. Light and electron microscopy findings in a long-term follow-up study. AB - Following intraperitoneal inoculation with coxsackie B3 virus all weaning Syrian golden hamsters (60 animals) developed severe myocarditis. In the acute phase, light and electron microscopy revealed massive cellular infiltration and myocytolysis in the myocardium which were most prominent on the 5th day and least obvious in 3 weeks. In the necrotic myocytes, mitochondria contained moderately electron dense inclusions different from the calcified granules seen in the myocardium of mice with coxsackie B3 virus myocarditis. Macrophages ingested and digested necrotic cell debris, leaving moderate fibrosis but no calcification in the myocardium. Viruses were isolated from the myocardium on the 3rd to 9th day, and virus particles were seen in a necrotic cardiocyte on the 9th day. In the chronic phase, most animals developed no cardiomegaly; light microscopy revealed minimal myocardial fibrosis; electron microscopy showed various degenerative changes in some cardiocytes. A few animals (two animals) developed significant cardiomegaly with moderate to marked myocardial fibrosis in the 6th and 14th month. In one heart there was marked biventricular dilatation. In these animals with cardiomegaly, ultrastructural changes of the myocardial cells were similar to those described in congestive cardiomyopathy in man. Golden hamsters appear to be a unique model for a study of the possible relationship between viral myocarditis and idiopathic cardiomyopathy in man. PMID- 6264180 TI - [Role of cyclic AMP in bacterial physiology. Advances of research since 1973]. PMID- 6264178 TI - [Treatment of whooping cough and whooping cough syndrome by cefoperazone (author's transl)]. AB - Clinical trial of cefoperazone (CPZ) for the treatment of whooping cough and whooping cough syndrome was performed and the following results were obtained. 1) In 18 cases suffering from whooping cough, CPZ was given 47 approximately 106 mg/kg/day (average 72 mg/kg/day) by intravenous route. The clinical efficacy rates judged by doctors in charge were 44% on the 3 rd day, 75% on the 7 th day, 86% on the period day. And in these cases, the clinical efficacy rates judged by committee members were 56%, 83% and 86%. 2) In 6 cases diagnosed as whooping cough syndrome, CPZ was given 49 approximately 96 mg/kg/day (average 59 mg/kg/day) by the same route. The clinical efficacy rates judged by doctors in charge were 67% on the 3 rd day, 80% on the 7 th day and 75% on the period day. And in these cases, those judged by committee members were 83%, 80% and 100%. 3) In 1 case, Bordetella pertussis was searched and showed 0.012 mcg/ml of MIC. It was eliminated on the 1 st day after administration. 4) Doctors in charge judged the utility of CPZ for whooping cough. Twelve cases were useful and 6 cases were slightly useful. 5) No side effects were observed except for elevation of GOT and LDH. These results suggest that CPZ might be useful drug against whooping cough. PMID- 6264181 TI - [A new strategy for immunoglobulin analysis (author's transl)]. PMID- 6264179 TI - [Effectiveness of pivmecillinam in biliary tract infection. Especially on comparison in pivmecillinam and ampicillin (author's transl)]. PMID- 6264182 TI - [A fundamental study on the method for the measurement of cyclic-AMP in human platelets (author's transl)]. PMID- 6264183 TI - [Complement hemolytic activity (CH50), C3 and C4 levels in serum and plasma of the patients with various liver diseases (author's transl)]. PMID- 6264184 TI - [Transcatheter arterial embolization therapy for hepatoma--assessment in blood chemistry (author's transl)]. PMID- 6264185 TI - [Meckel's diverticulum--report of a case and our experience (author's transl)]. PMID- 6264186 TI - [An anti-spermatozoan contraceptive, the ST film]. PMID- 6264187 TI - beta-Endorphin and related peptides. PMID- 6264188 TI - Prostaglandin E2 and cyclic nucleotides during anaphylactic shock in rats. AB - Anaphylactic shock was induced with ovalbumin in sensitized rats and the relationship between PGE2 and cyclic nucleotides in lung tissue and plasma histamine during anaphylactic shock was studied. PGE2 level and cyclic AMP/cyclic GMP ratio decreased with this ovalbumin-challenge, and the former reached a minimum value 40 sec after the challenge while the latter reached a minimum value 20 sec later. The plasma histamine level was elevated and reached a maximum value concomitant with the minimum value in the cyclic AMP/cyclic GMP ratio. Dibutyryl cyclic AMP elevated the PGE2 level significantly and inhibited the ovalbumin induced elevation of plasma histamine, however, this effect was abolished by the administration of indomethacin. PGE2 infusion elevated the cyclic AMP level as well as the cyclic AMP/cyclic GMP ratio, in a time-dependent manner, and inhibited the ovalbumin-induced elevation of plasma histamine during 10 min infusion. There was a significant correlation between the cyclic AMP level and the cyclic AMP/cyclic GMP ratio, both elevated by PGE2 infusion. Thus, anaphylactic elevation of the plasma histamine level results from a decrease in the levels of PGE2 in lung tissue rather than a decrease in the cyclic AMP/cyclic GMP ratio, albeit these decreases being coincident during anaphylactic shock. PMID- 6264189 TI - Brain benzodiazepine receptors and their rapid changes after seizures in the Mongolian gerbil. AB - To elucidate the physiological role of benzodiazepine receptors in convulsion, these receptors were studied in the brain of the Mongolian gerbil (Meriones unguiculatus), an animal model used for the study of epilepsy. Benzodiazepine binding sites in the gerbil brain were demonstrated using [3H]diazepam. The binding was saturable and stereospecific. Benzodiazepines inhibited [3H]diazepam binding to the membranes and their ability to inhibit the binding closely correlated with their potency as anticonvulsants. These results showed that the characteristics of the benzodiazepine receptors in the Mongolian gerbil were similar to those obtained from rat and human brain. Seizures increase the specific binding of [3H]diazepam to the membranes of all regions of the gerbil brain, the most remarkable increase seen in the striatum. Time course studies showed that the increase reached a maximum 10 min after the seizure and the binding returned to the control level within 20 min. The increase in specific [3H]diazepam binding was due almost entirely to shifts in the affinity of [3H]diazepam for its receptors. Thus, the seizures may not be due to changes in the benzodiazepine receptors, and seizures produce an increase in receptor binding, which may be related to a physiological modification of excessive excitation. PMID- 6264191 TI - [Exercise testing in chronic pulmonary emphysema (author's transl)]. PMID- 6264190 TI - Inhibitory effect of tiaramide of aggregation in vivo and on electrophoresis of rabbit platelets. AB - Effects of tiaramide, aspirin an indomethacin were studied on rabbit platelet aggregation in vivo and on platelet electrophoretic mobility. When tiaramide (6 mg/kg), aspirin (30 mg/kg) or indomethacin (1.3 mg/kg) was injected into the ear vein of rabbit during 60 sec, tiaramide only inhibited ADP-induced aggregation, 20 min after the injection. All three drugs prevented collagen-induced aggregation 20 and 120 min after the injection. Tiaramide and aspirin prevented aggregation 24 hours later. The inhibitory effects on the aggregation of tiaramide are presumably independent of prostaglandin synthesis, because malondialdehyde (a metabolite of PGG2) production was not influenced. Tiaramide reduced cyclic AMP levels in platelets after 20 min incubation, despite the ability of this agent to inhibit platelet aggregation. Tiaramide, aspirin and indomethacin per se has no effect on platelet electrophoretic mobility, while tiaramide prevented the decrease in the mobility produced by ADP. Tiaramide and aspirin also depressed the decrease in the mobility produced by collagen. PMID- 6264192 TI - [Antibody-dependent cell-mediated cytotoxicity (ADCC) in patients with sarcoidosis (author's transl)]. PMID- 6264193 TI - Regulation of cell-mediated immunologic reactivity to Moloney murine sarcoma virus-induced tumors. I. Cell and serum activity detected by leukocyte adherence inhibition. AB - Cell-mediated immunity and serum regulatory factors were studied in an in vitro system involving a spontaneously regressing, virus-induced tumor. Inbred BALB/c and CBA mice were inoculated with Moloney murine sarcoma virus and their peritoneal cells were tested for reactivity in leukocyte-adherence inhibition tests with extracts of syngeneic tumors. Sera from inoculated mice were tested for their effect on this reactivity. At the optimal dilution, tumor extracts induced significant reactions with cells from tumor-bearing mice (progressors) and from mice with regressed tumors (regressors); cells from normal mice and from mice with transplanted, chemically induced tumors were unaffected. Sera from progressor mice specifically blocked the reactivity of syngeneic cells. At the time of maximal tumor development, this blocking activity disappeared and the serum became unblocking: i.e., the regressor serum neutralized the blocking factor in progressor serum. The blocking or unblocking factors were tumor specific; no cross-reactivity occurred with similar factors related to the chemically induced tumor. Normal cells were not significantly affected by exposure to blocking and unblocking sera. The development of cellular immune reactivity and serum factors detected in vitro corresponded to the cycle of tumor progression and regression observed in vivo. PMID- 6264194 TI - Kinetics of cell replication of the uterine cervix. V. Behavior of DNA replicating tumor cells in invasive squamous carcinomas in mice. AB - The intratumoral migration of tritiated thymidine ([3H]dThd)-labeled cells was recorded at various intervals (from 1 to 240 hr) in squamous invasive carcinomas of the cervix in 25 inbred C57Bl mice. Carcinomas were induced by local application of benzo[a]pyrene for 5 months. This treatment was discontinued 7 days before the animals were killed. Cells were labeled by a single ip injection of 6 muCi [3H]dThd/g body weight. The tumors were divided by the aid of an ocular scale into three equal compartments: a peripheral zone, an intermediate zone, and a central zone. Many densely (initially) labeled cells were present in the peripheral and intermediate zones 1-48 hours after the injection of isotope, but these cells decreased in number in the intermediate zone and had disappeared from the peripheral zone by 96 hours. Conversely, densely labeled cells were absent in the center of the tumor during the first 24 hours, but they were recorded in large numbers at 48 hours. It was concluded that in addition to already known mechanisms of cell migration in solid tumors (e.g., invasion of the surrounding normal tissue, intravascular migration, migration toward the center of individual tumor nests, and cell exfoliation), there is intratumoral migration of cells toward the center in cervical carcinomas in mice. PMID- 6264195 TI - Histone H5 in the immature blood cells of chickens with leukosis induced by avian leukosis virus strain E26. AB - Whole histone was isolated from the immature cells of the peripheral blood of White Leghorn chickens, line 151, with leukosis experimentally induced by avian leukosis virus, strain E26 (ALV-E26). Histone H5 was demonstrated in all samples of these cells and was characterized by electrophoresis in polyacrylamide gel, extraction with perchloric acid, amino acid analysis, and immunodiffusion in agarose gel. Histone H5 was not detected in the myeloblasts of chickens with myeloblastosis caused by the avian myeloblastosis virus. It was concluded that the immature cells (IBC-E26) obtained from the peripheral blood of chickens responding positively to ALV-E26 belonged to the erythroid blood cell series and that ALV-E26 induced in vivo erythroblastosis but not myeloblastosis in chickens. The relative amount of histone H5 in IBC-E26 was two times higher than that in the erythroblasts obtained from the peripheral blood of chickens with erythroblastosis caused by avian erythroblastosis virus, strain R of Engelbreth Holm. Thus the erythroblasts in the circulating blood of chickens with leukosis induced by ALV-E26 seemed to be more differentiated. PMID- 6264197 TI - Studies on the components of kallikrein-kinin system and treatment of male infertility. PMID- 6264196 TI - Analysis of a pathology review of patients with lung tumors. AB - The rates of agreement and patterns of disagreement in the classification of lung tumors were evaluated for a pathology panel review of 476 patients with lung cancer. The panel review consisted of three independent diagnoses made in accordance with the criteria of the Working Party for Therapy of Lung Cancer. At least two of the three pathologists agreed as to the major cell classification in 94% of the patients. In 67% of the evaluations, there was agreement among the three pathologists. Small-cell carcinoma and epidermoid carcinoma were the most consistently evaluated classes, followed by adenocarcinoma and large-cell carcinoma. The poorly differentiated categories provided the greatest source of difficulty in discriminating among major histologic classes. For an initial diagnosis of large-cell carcinoma, 14% of the second classifications were poorly differentiated epidermoid carcinoma, and 20% were poorly differentiated adenocarcinoma. For an initial diagnosis of small-cell carcinoma, 11% of the second independent evaluations classified the carcinoma as other than small-cell. The most likely alternative diagnosis was large-cell carcinoma (5%). PMID- 6264199 TI - In vivo "culture" of a transporting renal epithelial monolayer. PMID- 6264198 TI - Mechanism of osmotic diuresis. AB - Mannitol might inhibit paracellular reabsorption of water and sodium chloride in the proximal tubules by reducing the osmotic driving force. We examined this hypothesis in anesthetized dogs. Bicarbonate reabsorption was kept constant by sodium bicarbonate infusion, and transcellular sodium chloride reabsorption was inhibited by ethacrynic acid. The glomerular filtration rate (GFR) was varied by altering renal perfusion pressure. Mannitol infusion reduced sodium chloride reabsorption from 62 +/- 5% to 33 +/- 5% of the filtered load. The calculated increase in reabsorbate osmolality, averaging 82 +/- 6 mOsm/kg H2O, was due to sodium bicarbonate and equalled the increase in plasma osmolality. Mannitol concentration averaged 81 +/- 7 mM in plasma and 101 +/- 12 mM in urine. A linear relationship between reabsorption and GFR (glomerulo-tubular balance) was maintained over the same range of GFR before and after mannitol infusion. Mannitol infusion reduced sodium chloride reabsorption from 2.6 to 1.4 moles for each mole of sodium bicarbonate reabsorbed. During mannitol infusion, acetazolamide inhibited sodium bicarbonate reabsorption as in control experiments, but reduced sodium chloride reabsorption less. We conclude that reduced water reabsorption increases sodium bicarbonate concentration in the paracellular fluid as much as mannitol concentration is raised in the plasma and glomerular filtrate. Along the proximal tubules, net osmotic force is progressively reduced as mannitol concentration rises, accounting for reduced water and sodium chloride reabsorption. PMID- 6264200 TI - Decreased phosphate reabsorption after renal transplantation: Evidence for a mechanism independent of calcium and parathyroid hormone. PMID- 6264201 TI - Fatal lymphoproliferation and acute monocytic leukemia-like disease following infectious mononucleosis in the elderly. AB - Three elderly patients are reported, in whom serologically confirmed recent infectious mononucleosis is followed by fatal lymphoproliferation (case 1), by acute monocytic leukemia (case 2), and by acute probably monocytic leukemia (case 3). PMID- 6264202 TI - [Possibilities for a practice of cancer after-care]. PMID- 6264203 TI - [Psychosocial after care]. PMID- 6264204 TI - [Nursing education: frustration in nursing]. PMID- 6264205 TI - [Nursing education. Teaching of a technology: nursing care]. PMID- 6264206 TI - [Offers for employment yesterday and today]. PMID- 6264207 TI - [Education in intensive care: are the nurses satisfied? Results of a survey]. PMID- 6264210 TI - [Maternal behavior in anthropoid apes]. PMID- 6264211 TI - [A life experience: health volunteer]. PMID- 6264208 TI - [Ambulatory care nursing: introduction to a school]. PMID- 6264209 TI - [A new Kardex system with more nursing indications coming? Documentation of the nursing process: report on the WHO seminar from 8-10 December 1980 in Bern]. PMID- 6264212 TI - [Marjorie Duvillard and continued education of nurses. Interview by Edwige Pittet]. PMID- 6264213 TI - [Physical experience in the education for nursing]. PMID- 6264214 TI - [Respiration therapy]. PMID- 6264215 TI - [Patient's fear prior to operations for orthopedic interventions]. PMID- 6264216 TI - [Operating room nurses: the information group of supervisory operating room nurses]. PMID- 6264217 TI - [Bechterew's disease: practical guidelines of the Swiss Society Bechterew's Disease]. PMID- 6264218 TI - [Care of patients with a bladder catheter]. PMID- 6264219 TI - [Observations on illness]. PMID- 6264220 TI - [General problems in cancer after care. Employment and pension legislation often hinder after care]. PMID- 6264221 TI - Diagnostic exercise. Mucinous adenocarcinomas of the colon in a cotton-topped tamarin. PMID- 6264222 TI - Detection of antibodies to Herpesvirus simiae and Herpesvirus hominis in nonhuman primates. AB - Sera from nonhuman primates, predominantly Macaca species, were assayed by a serum neutralization test for antibodies to antigenically related Herpesvirus simiae (B virus) and Herpesvirus hominis type 1. The data indicate that there would have been approximately 50% error in the diagnosis of Herpesvirus simiae infection if these sera had been tested only against Herpesvirus hominis antigen. The role of active guinea pig complement in the serum neutralization test was also evaluated and found to be required by many of the sera for reproducible and enhanced virus neutralization, particularly for B virus antibody determination. A plaque reduction assay was found to be highly sensitive, especially when complement (2.5-5.0 hemolytic units) was added, but impractical for large-scale serum surveys. PMID- 6264223 TI - Isolation of an enterovirus (SV19) from baboons (Papio cynocephalus). AB - Inoculation of newborn mice with fecal samples from approximately 200 baboons (Papio cynocephalus) yielded an enterovirus (SV19) from four different animals. This virus previously had been found only in Asian monkeys (Macaca sp). PMID- 6264224 TI - delta 9-Tetrahydrocannabinol by GLC-MS validated radioimmunoassays of hemolyzed blood or serum. AB - A direct radioimmunoassay (RIA) of delta 9-tetrahydrocannabinol (delta 9-THC) in unextracted hemolyzed blood or serum is described. The dose-response curve in the range of 5-50 ng/mL (serum or blood) was linear on log-logit transformation and iterative weighted regression. Validation studies included testing for precision, accuracy and antibody specificity as well as confirmation of RIA results (marijuana smoker samples) by gas liquid chromatography-mass spectroscopy (GLC MS). This routine method will greatly augment cannabinoid investigative programs. PMID- 6264225 TI - The detection of tetrahydrocannabinol in blood: a comparative study. PMID- 6264227 TI - Parathormone and cyclic AMP production in human cryopreserved parathyroids. PMID- 6264228 TI - Effect of exogenous and endogenous ACTH on adrenocortical cyclic GMP in the rat. PMID- 6264226 TI - Evidence for a role of calmodulin in insulin release from pancreatic islets. PMID- 6264229 TI - 5'-p-fluorosulfonylbenzoyladenosine as an ATP site affinity probe for Na+, K+ ATPase. AB - We have investigated the suitability of 5'-p-fluorosulfonylbenzoyladenosine (FSBA) as an ATP site affinity probe for the canine kidney Na+, K+-ATPase. The purified enzyme is slowly inactivated by this compound in suitable buffers, losing about half of its activity over a two-hour period. The rate of inactivation is more rapid in 0.1 M KCl than in 0.1 M NaCl. Low concentrations of ATP protect the enzyme against inactivation, with half-maximal effects at 4 microM ATP in 0.1 M NaCl and 350 microM ATP in 0.1 M KCl. ADP also protects against FSBA inhibition, but AMP is ineffective when present at 100 microM levels. This pattern is consistent with the previously described nucleotide specificity of the Na+, K+-ATPase. Addition of protective amounts of ATP after inactivation has occurred does not restore enzyme activity, indicating that inhibition is irreversible. Measurement of the concentration-dependence of FSBA inactivation suggests an apparent Kd for binding of this compound well above 1 mM, the solubility limit of the analog. This finding is reinforced by the failure of 1 mM FSBA to compete effectively with ATP for the high-affinity ATP site of the enzyme. Nevertheless, attachment of the analog to this site is indicated by its ability to prevent [3H]-ADP binding in proportion to the number of sites it has inactivated. Studies with [3H]-FSBA show that about 1 mole of the analog attaches specifically to the alpha subunit per mole of enzyme inactivated. A similar amount of nonspecific labeling also occurs with negligible effect on enzyme activity. These findings suggest that FSBA may be useful in probing the topography of the high-affinity ATP binding site of the Na+, K+-ATPase and related enzymes. PMID- 6264230 TI - Release of adenosine by C1300 neuroblastoma cells in tissue culture. AB - Previous work in our laboratory led us to postulate that N2a cells release adenosine into growth medium, where it acts at the extracellular adenosine receptors to modulate the sensitivity of the cells to the cyclic AMP-elevating effect of adenosine [Green, RD, J Pharmacol Exp Ther 201:610, 1977]. We have now devised a high-performance liquid chromatographic (HPLC) procedure capable of quantitating the concentrations of adenosine in cells and tissue culture media. Growth media of N2a cells and a variant of N2a cells deficient in hypoxanthine guanine phosphoribosyltransferase (HGPRT-) contain 10-20 nM adenosine, while that of a variant deficient in adenosine kinase (AK-) is elevated severalfold. It appears that the concentration of adenosine in growth media is determined by both the rate at which it is released by cells into the medium and the rate at which it is metabolized by adenosine deaminase present in the serum in the growth medium. Both N2a and AK- cells release considerable amounts of adenosine into serum-free medium (SFM) over a short period. Adenosine release is greater from AK cells and is accelerated by erythro-9-(2-hydroxy-3-nonyl)-adenine (EHNA), a potent adenosine deaminase inhibitor. This accelerated release is retarded by dipyridamole and homocysteine. Surprisingly, dipyridamole and 4-(3-butoxy-4 methoxybenzyl)-2-imidazolidinone (Ro 20 1724), a potent phosphodiesterase inhibitor, stimulate basal adenosine release from N2a but not from AK- cells. It remains to be determined if this is due to an effect of these compounds on adenosine kinase. These results give further support for the hypothesis that adenosine in growth medium modulates the sensitivity of the cells to the cyclic AMP-elevating affect of adenosine, and furthermore they suggest that adenosine in growth media may tonically stimulate adenylate cyclase and affect processes controlled by the cyclic AMP:cyclic AMP-dependent protein kinase system. PMID- 6264231 TI - Cell-cell contact and growth regulation of pinocytosis in 3T3 cells. AB - In sub-confluent cultures of Balb/c-3T3 cells, pinocytosis rates were increased after exposure to specific growth factors (serum; platelet-derived growth factor, PDGF; epidermal growth factor, EGF). Conversely, as cells became growth-inhibited with increasing culture density, there was a corresponding decline in pinocytosis rate per cell. In order to test whether density-inhibition of pinocytosis was influenced either by the growth cycle or by cell contact independently of growth, cells were induced into a quiescent state at a range of subconfluent and confluent densities. Under such conditions, cell density did not significantly inhibit pinocytosis rate. When confluent quiescent cultures in 2.5% serum were exposed to 10% serum, the resulting round of DNA synthesis was accompanied by enhanced pinocytosis per cell, even though the cells were in contact with one another. Furthermore, in a SV40-viral transformed 3T3 cell line, both the growth fraction and the pinocytosis rate per cell remained unchanged over a wide range of culture densities. These studies indicate that density-dependent inhibition of pinocytosis in 3T3 cells appears to be secondary to growth-inhibition rather than to any direct physical effects of cell-cell contact. PMID- 6264232 TI - Direct linkage of EGF to its receptor: characterization and biological relevance. AB - A small portion of the 125I-EGF that binds specifically to intact cells or isolated membrane from a variety of sources becomes directly and irreversibly linked to EGF receptors. This provides a simple technique for affinity labeling the EGF receptor. Membranes isolated from the human epidermoid carcinoma cell line A431, which possesses extraordinarily high numbers of EGF receptors, gave rise to three major direct linkage complexes of MW = 160,000, 145,000, and 115,000. The time course for information of each is similar, showing that 125I EGF can form direct linkage complexes with several preexisting forms of the EGF receptor. The direct linkage of EGF to receptor is slow in comparison to 125I-EGF binding, but both processes have similar susceptibilities to competition by unlabeled EGF. EGF was modified chemically with the amino site-specific reagent, N-hydroxysuccinimidyl biotin. The biotinyl-EGF had a reduced capacity to engage in direct linkage complex formation with no concomitant reduction in its ability to bind to EGF receptors. Since native and biotinyl EGF have identical abilities to stimulate the uptake of 3H-thymidine into DNA when incubated with cultured murine 3T3 cells, the direct linkage of EGF to its receptor does not appear to play an important role in EGF-stimulated mitogenesis. PMID- 6264233 TI - Controlled proteolysis of EGF receptors: evidence for transmembrane distribution of the EGF binding and phosphate acceptor sites. AB - A small quantity of the 125I-EGF (epidermal growth factor) bound specifically to EGF receptors on the human epidermoid carcinoma cell line A431 associates covalently. The direct linkage complex formed migrates during gel electrophoresis as a single diffuse band of MW = 160,000-170,000. In contrast, direct linkage complexes of 160,000, 145,000, and 115,000 daltons are formed when EGF is incubated with membranes isolated from these cells; these arise from EGF receptor modification during membrane isolation. None of these modifications affected the affinity of the EGF binding site for 125I-EGF. The electrophoretic mobilities of the MW = 160,000 and 145,000 direct linkage complexes were similar to those of the major 32Pi-labeled products of the EGF-stimulated phosphorylation reaction described by Carpenter et al [Nature 276:409-410, 1978], indicating that proteolytic fragments of EGF receptors are the major phosphate acceptors in this reaction. EGF receptors on intact A431 cells accepted phosphate effectively from gamma-32Pi-ATP only when the cells were permeabilized with lysolecithin. This shows that the EGF binding and phosphate acceptor sites lie on opposing faces of the membrane. When the 145,000 dalton form of receptor is labeled with EGF or 32Pi and the labeled peptides subjects to tryptic hydrolysis under identical conditions, all phosphate is lost from high molecular weight products under conditions where the EGF-receptor covalent complex is converted largely to a 115,000 dalton form. This suggests that the phosphate acceptor site lies on the cytoplasmic side of the membrane on a region of receptor extending 30,000 daltons from the 115,000 dalton fragment containing the EGF binding site. PMID- 6264234 TI - Selective protein transport: identity of the solubilized phosvitin receptor from chicken oocytes. AB - By two independent methods, the solubilized receptor for phosvitin (PV) has a subunit MW of 116K. Affinity chromatography, showed that only 2 of the more than 25 proteins present in the total detergent solubilized oocyte membrane extract were retained on a PV-agarose column. These proteins of MW of 116K and 100K could be eluted from PV-agarose with free PV. By gel exclusion chromatography, the receptor-125I-PV complexes elute in the void volume of a Biogel A-1.5 column. When these void fractions were assayed gy SDS-PAGE only a single protein of MW of 116K was observed in addition to 125I-PV. PMID- 6264235 TI - Properties of receptors for epidermal growth factor in detergent solution: evidence for heterogeneous aggregated states. AB - Between 60% and 100% of epidermal growth factor (EGF) binding activity was recovered from membranes of the A431 human epidermoid carcinoma cell line treated with solutions containing the nonionic detergent Triton X-100. Approximately half of the recovered binding activity was sedimented at low centrifugal force and hence was operationally insoluble in nonionic detergent solution. Receptors in both the detergent-soluble and -insoluble fractions displayed similar affinities for 125I-EGF, and the values were in good agreement with those obtained for receptors in untreated membranes. The receptors in both fractions also formed identical direct linkage complexes with 125I-EGF in similar yield, providing no evidence for partitioning of different molecular species of EGF receptors in the detergent-soluble membrane fraction of Sepharose 6-B revealed heterogeneity of 125I-EGF binding activity; the smallest and most monodisperse peak of activity resolved by this technique was eluted at a Strokes radius of 95 A. Operationally soluble 125I-EGF binding activity also behaved heterogeneously during velocity sedimentation; more than half the activity sedimented more rapidly than the apparently monidisperse, 7S form. An average of less than half the nonionic detergent-solubilized activity recovered from 10 independent membrane preparations behaved as an apparently monodisperse entity. Since a maximum of 60% of 125I-EGF binding activity was operationally soluble, less than 25% of the total EGF binding activity was recovered in an apparently monodisperse form. The remaining 75% of the EGF receptors displayed a marked tendency to exist as aggregates in nonionic detergent solutions. PMID- 6264236 TI - Sera of patients with hairy cell leukemia immunoprecipitate EBV-related antigens. PMID- 6264237 TI - [Infections due to herpes-varicella viruses in Hodgkin's disease (author's transl)]. AB - The infections due to herpes-varicella viruses occurring in 191 patients with Hodgkin's disease form the basis of this report. There were overall 41 episodes (26.7%) in 40 patients, distributed as follows: varicella in three cases, atypical herpes-varicella in two cases, and herpes zoster in 36 cases, the latter showing systemic spread in seven instances, one to the central nervous system (myelitis) and six to the skin. The mortality was 2.5% of all infections, and 33% of the varicella cases. Morbidity was apparent as postherpetic neuralgia in seven patients (19.4%), postherpetic paraplegia in one case (2.5%), and severe thrombocytopenia in another case (2.5%). The statistical study of the factors contributing to the development of reactivation episodes demonstrated that neither age, sex, or previous splenectomy were influential. The results obtained in relation to the stage and histologic type of Hodgkin's disease can not be fully evaluated because of the artifact introduced by other variables such as type of therapy and observation time. There was a clear relationship with the aggressiveness of therapy, because 81.7% of the viral episodes occurred in patients submitted to total radiotherapy with or without chemotherapy, or with partial radiotherapy plus chemotherapy. In the patients with systemic spread there was a clear relationship with prior splenectomy (p less than 0.005). The clinical features of these patients are commented upon. PMID- 6264238 TI - [Partial resistance to thyroid hormones in a patient with a euthyroid goiter (author's transl)]. AB - This case report deals with a 40 year-old female with goiter, elevated levels of peripheral thyroid hormones without the clinical picture of hyperthyroidism, and an exaggerated response to TSH and TRH. The fact that a feedback conversion appeared after progressive doses of T3 is outlined. Taking into account the elevated T3/T4 ratio, the high rT3, and the fact that all other pituitary hormones remained normal in the presence of increased levels of thyroid hormones, it is concluded that the case was one of incomplete universal resistance of the thyroid hormone receptors. Other individual and familial reported cases are reviewed, and emphasis is made on the fact that the receptors have been normal when studied. PMID- 6264239 TI - Familial non-chromaffinic paragangliomas (glomus tumors) : clinical aspects. AB - The clinical aspects of a study of a large family suffering from glomus tumors are presented. A great deal of fragmentary information is obtained from the literature, but never before has so much information been obtained from one single family. The aim of this study was to screen the individual members of this family by careful history, with special interest taken in symptoms which could be indicative of glomus tumors, and by a physical examination. Because these tumors may be without symptoms or signs, the screening was extended with dynamic angioscintigraphy. PMID- 6264241 TI - [Primary carcinoma of the liver per 731 autopsies performed at the Military Hospital in Split (author's transl)]. PMID- 6264240 TI - [The frequency of HBsAg in plasma donors, and the incidence of anti HBs, anti HBc, anti HBe and anti HAV in HBsAg negative plasma donors in Zagreb (author's transl)]. PMID- 6264243 TI - The development of a radioimmunoassay for ranitidine in biological fluids. PMID- 6264242 TI - Effects of continuous angiotensin I-converting enzyme blockade on blood pressure, sympathetic activity and renin-angiotensin system in stroke-prone spontaneously hypertensive rats. PMID- 6264244 TI - Comparative study on the effect of morphine and the opioid-like peptides in the vas deferens of rodents: species and strain differences, evidence for multiple opiate receptors. PMID- 6264246 TI - Beta-adrenoceptors of human lymphocytes: decrease in affinity of agonist for ( )3h-dihydroalprenolol binding sites by cytoplasmic fractions. PMID- 6264245 TI - Morphine withdrawal causes subsensitivity of adrenergic receptor response. PMID- 6264247 TI - Multiple benzodiazepine receptors: evidence of dissociation between anticonflict and anticonvulsant properties by PK 8165 and PK 9084 (two quinoline derivatives). PMID- 6264248 TI - The pituitary-adrenal response to ether stress in the spontaneously hypertensive and normotensive rat. PMID- 6264249 TI - Cytosol stimulation of pregnenolone synthesis by isolated adrenal mitochondria. PMID- 6264250 TI - The in vivo differentiation of opiate receptors: introduction. PMID- 6264251 TI - Multiple opioid receptors: a little about their history and some implications related to evolution. PMID- 6264252 TI - Simple in vivo tests that differentiate prototype agonists at opiate receptors. PMID- 6264253 TI - Discriminative stimulus effects of narcotics: evidence for multiple receptor mediated actions. PMID- 6264254 TI - The significance of physiological [Ca2+] and [Mg2+] for in vitro experiments on synaptic transmission. PMID- 6264256 TI - Hyperactivity following injection of a glutamate agonist and 6,7-ADTN into rat nucleus accumbens and its inhibition by THIP. PMID- 6264255 TI - Benzodiazepine receptor: heterogeneity in rabbit brain. PMID- 6264257 TI - A new approach to the treatment of atherosclerosis and trapidil as an antagonist to platelet-derived growth factor. PMID- 6264258 TI - Alterations in T3 and T4 receptor binding in fasting and diabetes mellitus. PMID- 6264259 TI - The effect of dexamethasone, diet control and hyperglycemia on murine hepatic T3 receptors. PMID- 6264260 TI - Catecholamine-thyroid hormone interactions in liver and adipose tissue. PMID- 6264261 TI - The melatonin rhythm generating system: developmental aspects. PMID- 6264262 TI - The effects of thyrotropin-releasing hormone on cyclic AMP accumulation in rabbit cerebral cortical tissue in the presence and absence of CNS depressants. PMID- 6264263 TI - A lysosomal enzyme involved in diphosphatidylglycerol degradation. AB - A soluble lysosomal phosphodiesterase in rat liver that hydrolyzes monoacylglycerophosphorylglycerophosphorylglycerol (AGPGPGase) was shown to be distinct from a lysosomal acid phosphodiesterase IV (PDase IV) which catalyzes the hydrolysis of bis(p-nitrophenyl) phosphate. The criteria used to distinguish lysosomal AGPGPGase from PDase IV were: separation on ion exchange celluloses, dissimilar inhibition patterns and different rates of inactivation on concentration. The lysosomal PDase IV activity was competitively inhibited by inorganic phosphate with a Ki value of 0.33 mM phosphate and was inhibited by a number of organophosphoryl compounds including AGPGPG, phosphatidylcholine, phosphatidylinositol, ATP and 4-methylumbelliferylpyrophosphate. PMID- 6264265 TI - [Exogenous poisoning polyneuropathies]. PMID- 6264264 TI - [Combined and radiation treatments of malignant lacrimal gland tumors]. PMID- 6264266 TI - Common oral mucosal diseases. PMID- 6264267 TI - [Experience of a "group-apartment" self-managed by 3 discharged psychiatric patients after long institutionalization. Remarks on the experiment and working hypotheses]. PMID- 6264269 TI - [Evaluation of the main intestinal parasitic diseases in 860 Ivory Coast children from 13 different villages. 2. Schistosoma mansoni (author's transl)]. PMID- 6264268 TI - [Evaluation of the main intestinal parasitosis in 860 Ivory Coast children from thirteen different villages (author's transl)]. AB - A survey has been carried out in 2 forest villages, 9 savanna villages and 2 Abidjan suburb districts. A total sample of 860 children aged between 6 and 15, has been examined. Data tabulation indicated a prevalence of the main intestinal nematodes, of S. mansoni and of E. histolytica, with variable respective percentage. Ascaris lumbricoides affected 26 p. 100 of children but is less frequent in the savanna areas than in the forest areas. Trichiuris trichiura affected 1 child out of 4 but infestation rate reached 76 p. 100 in the Abidjan suburb district. Necator americanus is the most frequently detected parasite (67 p. 100) and is more frequent in the forest areas than in the 2 savanna villages. E. histolytica has an uniform and low (5 p. 100) geographical distribution. S. mansoni has such an irregular distribution that no extrapolation is possible from the results obtained to the geographical area considered. Its infestation rates is from 1 p. 100 to 60 p. 100 with important differences inside small geographical zones. PMID- 6264270 TI - Postnatal development and sex differences in hepatic phosphatidate phosphohydrolase activity in the rat. AB - The mechanism leading to the difference in hepatic triacylglycerol metabolism between female and male rats was investigated by studying the ontogeny of hepatic soluble phosphatidate phosphohydrolase activity in feeding animals of both sexes. A sevenfold increase occurred within 12 hr of birth, returning to the adult level during the third postnatal day. The changes in enzyme activity were followed by similar changes in hepatic triacylglycerol concentrations. A sex difference was observed only in the adult rats, where the enzyme activity in the livers of feeding female rats was about 25% higher than that in the feeding males. The effects of gonadectomy and sex steroids were studied in a separate series of experiments on fasting animals. The activity of the soluble enzyme was 65% higher in the intact female rats than in the males, and that of the microsomal enzyme 130% higher. The activity ratio between the soluble and microsomal enzyme in the male rats was 4.3 on a liver wet weight basis with the methods used. Gonadectomy increased the soluble and microsomal activities by 25% and 80% respectively within 6 wk in the male rats. The soluble and microsomal activities were still at the same control levels 2 wk after the gonadectomy, the subcutaneous implants of testosterone or estradiol resulting in 10-fold increases in plasma hormone levels had no effects on these enzyme activities, although testosterone caused 50% decrease in the hepatic triacylglycerol concentration. These data indicate that, if hormonally mediated, the postnatal increase in phosphatidate phosphohydrolase activities is not related to sex steroids and also suggest that the basis of the sex difference in hepatic soluble phosphatidate phosphohydrolase activity remains to be established. PMID- 6264271 TI - One and two codon insertion mutants of bacteriophage f1. AB - Simple methods for introducing one or two extra codons of genetic information into the f1 genome in vitro have been devised. The methods use various combinations of enzymes to insert three or six base-pairs into the RF1 DNA of the bacteriophage. Since such insertions do not cause frameshifts in coding regions, a number of these mutants are viable. Several such mutants were mapped and characterized. The methods described and variations of them can be applied to other circular DNA genomes. PMID- 6264272 TI - Initiation of DNA replication in Bacillus subtilis. V. Role of DNA gyrase and superhelical structure in initiation. PMID- 6264273 TI - Effect of DNA gyrase inhibitors on gene expression of the cysteine regulon. AB - Nalidixic acid inhibits the expression of those cysteine genes which are regulated by the cysB product, it has no affect, however, on the constitutively expressed cysE gene. The expression of cysteine genes in a strain carrying a mutation in the nalA locus is resistant to this drug. Novobiocin affects the expression of cysteine genes similarly to nalidixic acid. The effect of nalidixic acid on the expression of genes in a cysteine constitutive mutant was studied. PMID- 6264274 TI - Isolation and mapping of Escherichia coli K12 mutants defective in Tn9 transposition. AB - Five mutants (called tnm) of Escherichia coli with impaired ability for transposition of Tn9 were isolated after treatment with ethyl methanesulfonate (EMS) or N-methyl-N'-nitro-N-nitrosoguanidine (NG). The map locations of the tnm mutations were determined by a combination of Hfr matings, F' episome complementation and P1 transductional mapping. The data obtained show that the five tnm mutations are located near 91 min on the Escherichia coli linkage map and are cotransducible with the metA marker with a frequency of 3%-4%. Introduction of F' plasmids containing this region complements the Tnm- phenotype for the two mutants tested i.e. tnm-1 and tnm-2 are recessive in tnm+/tnm- merodiploids. PMID- 6264275 TI - Mutation in Escherichia coli during substrate-accelerated death. AB - Substrate-accelerated death was studied in lactose-limited cultures of Escherichia coli WP2 trp- and E. coli WP2 trp+. During starvation of E. coli WP2 trp- the viable count decreased while the number of trp+ revertants increased. Addition of 7.5 mM-cAMP to the starvation medium prevented the death of the trp cells but not the increase in the number of trp+ revertants. As starvation of pure cultures of trp+ revertants did not result in death it suggests that the level of cAMP in trp- cells was lower that in trp+ cells. Addition of benzyl penicillin, nalidixic acid, novobiocin or rifampicin did not affect the viable counts thus indicating that neither cryptic growth not DNA replication occurred; however, in the presence of novobiocin there was no increase in the number of trp+ revertants. The possibility of a constitutive error-prone DNA repair mechanism is considered. PMID- 6264276 TI - Review. Endothelial vesicles. PMID- 6264278 TI - [The benzodiazepine receptor: properties and significance for pharmacology, psychiatry and neurology]. PMID- 6264277 TI - [Experimental study of the neurotoxicity of cyclohexanol and cyclohexanone]. PMID- 6264279 TI - Cefotaxime sodium (Claforan). PMID- 6264280 TI - Cis-dichlorodiammineplatinum (II) and VP 16-213 combination chemotherapy for non small cell lung cancer. AB - Twenty-three patients with non-small cell lung cancer were treated with a combination of cis-dichlorodiammineplatinum (II) 100 mg/m2 IV on day 1 and VP 16 213 80 mg/m2 IV on days 1-3. Eighteen patients are evaluable for response. Seven partial remissions with a median duration of 3 months (range, 1-13+) have been observed. Three patients exhibit stable disease, and eight patients show tumor progression. Overall survival was 5+ months (range, 1-13+); 7.5 months (range, 3 13+) for responders and 3+ months (range, 1-9+) for non-responders. Hematologic toxicity was acceptable, but poor subjective tolerance (nausea, vomiting, loss of appetite) was the main factor limiting treatment duration. PMID- 6264281 TI - [Myocarditis caused by enteroviruses in infants. 3 cases in a suburban hospital]. PMID- 6264284 TI - [Application of spin labels in studying DNA structure and function]. PMID- 6264283 TI - [Use of triplet state exchange disactivation phenomenon for the study of structure and electron conductivity of proteins]. AB - A method for studying protein structure and estimating its electron conducting properties is proposed. The method is based on the kinetic recording of exchange quenching triplet labels and probes phosphorescence by chromophores or paramagnetic centres. It is shown that different types of exchange interactions (spin exchange, exchange energy transfer) between centres with distance R are described approximately by an equation (I = I0 exp-2R/L) where L changes from 0.7 A (absence of electron coupling--system of type I) to 6.5 A (strong electron coupling--system of type II). I (sec-1) corresponds to exchange energy transfer rate constant or exchange integral in the case of spin exchange. Life-times of excited triplet state eosin-isotiocionate labels connected with the terminal NH2 groups of the following preparations were measured by the method of kinetic phosphorescence decay recording: human oxyhemoglobin, methemoglobin, F- and CN methemoglobin, metmyoglobin, F- and CN-metmyoglobins. The influence of lysozyme of the nitroxyl spin label bound to His-15 group on the phosphorescence spectrum was investigated. The analysis of our and literature data on the exchange interactions between the centres localized on the protein with known structure (hemoglobin, myoglobin, lysozyme, carboangidrase, bacterial ferredoxin) permit us to conclude that in the examined cases the experimental values correspond to model systems of type I and are different from the dependence in systems of type II by 5--15 order. This allows us to use equation (I) for estimation of the distances between the centres on proteins. PMID- 6264285 TI - [Isotope effects on electron tunneling reactions in biological systems conformational mobility of proteins]. AB - Effects of D2O substitution on electron transport reactions in proteins were analysed on the basis of generally adopted ideas of electronic vibration interactions and conformational mobility of macromolecules. At the molecular level, a mechanism for cytochrome c oxidation was established. On the basis of general viscosity and elasticity properties of proteins, the effects of temperature and chemical composition of the medium on conformational relaxation were analysed. For chromatophores of photosynthetising bacteria, a mechanism is discussed by which abnormal effects of temperature and abnormal isotope effects may be exercised on charge recombination. PMID- 6264286 TI - Herpesvirus (HV) infection in newborns. PMID- 6264282 TI - ACTH stimulation on cholesterol side chain cleavage activity of adrenocortical mitochondria. Transfer of the stimulus from plasma membrane to mitochondria. AB - Adrenocortical mitochondrial cholesterol side chain cleavage reactions are regulated by the influence of pituitary ACTH. The mechanism of the stimulation involves adenyl cyclase, cAMP-dependent protein kinase, cholesterol esterase, and ribosomal labile protein synthesis. Through these reactions the stimulus reaches the mitochondrial side chain cleavage enzyme system. In this review article, the current implications on the stimulus transfer from the plasma membrane to the mitochondrial inner membrane are summarized. In particular the availability of cholesterol to P-450scc was discussed in terms of the distribution of cholesterol molecules in the membranes. PMID- 6264287 TI - The role of proteases in experimental glucocorticoid myopathy. AB - Mature, male, New Zealand white rabbits were treated with the synthetic glucocorticoid betamethasone (0.3 mg/kg body weight/day) for 2 weeks. The glucocorticoid treatment caused a 30% decrease in muscle weight of the type 2 psoas muscle, but had no apparent effect on the type 1 soleus muscle. Cathepsin D activity was elevated twofold in the psoas muscle of treated rabbits, a finding suggesting an active role for lysosomes in mediating muscle breakdown in glucocorticoid-induced myopathy of the rabbit. There was no detectable alkaline serine protease activity in the muscles from either treated or control rabbits. Alkaline protease is localized in mast cells in some species, particularly the rat. Toluidine blue staining for mast cells was absent in rabbit muscles, a finding indicating that this species does not contain these cells. This protease, previously implicated in glucocorticoid myopathy, apparently plays no role in rabbit myopathy. There was no detectable elevation of the Ca-activated protease in muscles from glucocorticoid-treated animals. This finding suggests that if this protease plays a role in muscle degradation, its activity is controlled in vivo by special conditions (such as elevated CA levels, inhibitors, and compartmentalizations). PMID- 6264288 TI - Inherited canine giant axonal neuropathy. AB - To date, a single case of canine giant axonal neuropathy (GAN) has been recorded. The present report describes the disease in 3 more dogs from the second litter produced by the parents of the original case. Regular clinical and electrophysiological examinations were carried out on all 11 dogs of the second litter. At 14--16 months of age, 3 dogs developed slight posterior ataxia which progressed to a severe lower motor neuron disturbance involving only the hind legs. During this period, each dog began to regurgitate food as a result of megaesophagus. From 12 months of age, there was a progressive reduction in the amplitude of the evoked muscle action potential. Biopsy of the tibial fascicular nerve at 16 months of age confirmed that all 3 dogs had GAN, with numerous swollen unmyelinated fibers and less frequent enlarged myelinated fibers containing accumulated neurofilaments. PMID- 6264289 TI - Microanalysis of perineural calcification in diabetic nephropathy. AB - Three different microanalytical methods were used to identify calcium deposits in the sciatic nerve perineurium of a 33-year-old woman who died after developing nephropathy, retinopathy, and neuropathy as complications of diabetes. Scanning electron microscopic x-ray microanalysis (SEM-XMA) enabled localization of calcium and phosphorus elements to the perineurium in whole nerve cross sections. With SEM-XMA and scanning-transmission electron microscopic x-ray microanalysis (STEM-XMA) of the minute crystallites in the perineurium, the approximate relative amounts of calcium and phosphorus in the deposits were found to correspond to those in calcium hydroxyapatite. Finally, the crystallites were specifically identified by selected area electron diffraction, and were found to be composed mainly of calcium hydroxyapatite. PMID- 6264290 TI - Concentric laminated bodies. PMID- 6264291 TI - Glomerulopathy associated with cytomegalovirus viremia in renal allografts. AB - We investigated the relation between cytomegalovirus (CMV) infection and renal allograft dysfunction in 14 patients. In seven instances (including two successive transplants in one patient), allograft dysfunction occurred during clinically manifest, viremic CMV infection. In five of these, biopsies revealed little or no tubulointerstitial change but a distinctive, diffuse glomerulopathy characterized by enlargement or necrosis of endothelial cells and accumulation of mononuclear cells and fibrillar material in glomerular capillaries. Two of these allografts recovered their function, both with cessation of high-dose immunosuppression. Biopsies in the other 10 patients revealed predominantly tubulointerstitial changes typical of cellular rejection, and most of these patients did not have viremia. One additional patient, studied prospectively, manifested both forms of allograft injury: tubulointerstitial changes occurring two weeks after transplantation and responding to increased immunosuppression, and CMV-associated glomerulopathy occurring seven weeks after transplantation and responding to decreased immunosuppression. We conclude that viremic CMV infection can cause acute glomerular injury and that recovery may be favored by a decreased in immunosuppressants. PMID- 6264292 TI - Acyclovir prophylaxis of herpes-simplex-virus infections. AB - We conducted a double-blind, placebo-controlled study of acyclovir prophylaxis against infection with herpes simplex virus (HSV) in 20 seropositive recipients of bone-marrow transplants. Acyclovir or placebo was administered for 18 days, starting three days before transplantation. Culture-positive HSV lesions developed during the study in seven of the 10 patients who received placebo. In contrast, no such lesions appeared in the 10 patients who received acyclovir (P congruent to 0.003). None of the patients had evidence of drug toxicity. Five of the patients treated with acyclovir had mild culture-positive HSV infections after cessation of the drug, and two additional patients shed virus without having lesions. Acyclovir appears to be a potent inhibitor of HSV replication. Although acyclovir does no appear to eradicate latent infection, it can provide effective prophylaxis against reactivated infections. PMID- 6264293 TI - Peptide hormone-induced receptor mobility, aggregation, and internalization. PMID- 6264294 TI - Adverse reactions to intrapleural BCG. PMID- 6264295 TI - Small-cell carcinoma with ectopic ACTH secretion. PMID- 6264296 TI - Exanthem subitum not associated with rotavirus. PMID- 6264298 TI - Low temperature sustains inhibition of angiotensin-converting-enzyme activity in serum from patients taking captopril. PMID- 6264297 TI - Immunoregulatory T cells in mononucleosis and toxoplasmosis. PMID- 6264299 TI - Secondary maternal cytomegalovirus infection causing symptomatic congenital infection. PMID- 6264300 TI - Risk of recurrence after first episodes of genital herpes. Relation to HSV type and antibody response. AB - To define risk factors associated with recurrent genital herpes-simplex-virus infection caused by either Type 1 or 2 herpesvirus (HSV-1 or HSV-2), we prospectively studied 137 patients with a first symptomatic episode of the disease and 87 with a recurrent episode. First episodes were divided into 78 primary infections (no antibodies to HSV in acute-phase serum) and 59 nonprimary infections (antibodies present). HSV-1 infections were less frequent and less likely to recur than HSV-2 infections. Fifteen per cent of primary first episodes were caused by HSV-1, as compared with 3 per cent of nonprimary first episodes and 2 per cent of recurrent episodes. Moreover, during follow-up of first-episode patients, only 14 per cent of HSV-1 infections recurred, as compared with 60 per cent of HSV-2 infections. Recurrences were more likely to follow an index recurrent episode than an index first episode, whether primary or nonprimary, and were more likely to occur in men than in women. Among patients with primary HSV-2 infections, the probability of recurrence was directly related to the presence and titer of neutralizing antibody to HSV-2 in convalescent-phase serum. PMID- 6264301 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 32-1981. PMID- 6264302 TI - Ultrastructural changes produced by ketoconazole in the yeast-like phase of Paracoccidioides brasiliensis and Histoplasma capsulatum. AB - The ultrastructural changes produced by ketoconazole in the yeast-phase of H. capsulatum and P. brasiliensis were studied by means of scanning and transmission electron microscopy. The observed alterations on both fungi were very similar to those induced by the same drug on the ultrastructure of C. albicans. These alterations include surface changes, abnormal membrane proliferation, fatty degeneration of the cytoplasm and lysis of the subcellular organelles. P. brasiliensis seems to be more sensitive to ketoconazole than H. capsulatum, since the necrosis of most of the cells was obtained in the former at a concentration of 0.1 microgram/ml and in the latter at 1 microgram/ml. PMID- 6264303 TI - The transmission and control of gonorrhea. PMID- 6264304 TI - Molecular analysis of the unc-54 myosin heavy-chain gene of Caenorhabditis elegans. AB - The properties of a small internal deletion mutant, E675, have been exploited in the molecular cloning of the unc-54 gene. This mutation uniquely identifies unc 54 sequences as molecules of altered length in E675 and provides a genetic and physical marker for the active gene, its messenger RNA and its protein product. PMID- 6264305 TI - Sodium channels need not open before they inactivate. PMID- 6264306 TI - K+ channels close more slowly in the presence of external K+ and Rb+. PMID- 6264308 TI - Isolation of virus from brain after immunosuppression of mice with latent herpes simplex. PMID- 6264307 TI - Transcription of single-copy vitellogenin gene of Xenopus involves expression of middle repetitive DNA. PMID- 6264309 TI - Cell sorting, cell differentiation and cyclic AMP. PMID- 6264310 TI - Primary structure, gene organization and polypeptide expression of poliovirus RNA. AB - The primary structure of the poliovirus genome has been determined. The RNA molecule is 7,433 nucleotides long, polyadenylated at the 3' terminus, and covalently linked to a small protein (VPg) at the 5' terminus. An open reading frame of 2,207 consecutive triplets spans over 89% of the nucleotide sequence and codes for the viral polyprotein NCVPOO. Twelve viral polypeptides have been mapped by amino acid sequence analysis and were found to be proteolytic cleavage products of the polyprotein, cleavages occurring predominantly at Gln-Gly pairs. PMID- 6264311 TI - Demonstration of a specific dynorphin receptor in guinea pig ileum myenteric plexus. PMID- 6264312 TI - Glutamate-preferring receptors regulate the release of D-[3H]aspartate from rat hippocampal slices. PMID- 6264313 TI - Transcription of immunoglobulin heavy-chain sequences from the excluded allele. PMID- 6264314 TI - An aminoacyl tRNA synthetase binds to a specific DNA sequence and regulates its gene transcription. AB - Alanine tRNA synthetase represses transcription of its own gene by binding specifically to a palindromic sequence which flanks the gene's transcription start site. Transcription repression is greatly enhanced by elevated concentrations of the cognate amino acid. The amino acid effect is caused by direct association of the ligand with the synthetase, which in turn mediates tighter binding to the DNA. PMID- 6264315 TI - Functional EGF receptors are present on mouse embryo tissues. PMID- 6264316 TI - Idiosyncratic platelet responses to human tumour cells. PMID- 6264317 TI - Sequential appearance of Epstein-Barr virus nuclear and lymphocyte-detected membrane antigens in B cell transformation. PMID- 6264318 TI - Differences between germ-line and rearranged immunoglobulin V kappa coding sequences suggest a localized mutation mechanism. PMID- 6264319 TI - Multiple sequences related to classical histocompatibility antigens in the mouse genome. PMID- 6264320 TI - Homologous tyrosine phosphorylation sites in transformation-specific gene products of distinct avian sarcoma viruses. PMID- 6264321 TI - Purified lambda regulatory protein cII positively activates promoters for lysogenic development. AB - The bacteriophage lambda regulatory protein, cII, has been purified and shown to activate positively RNA transcription from the two phage promoters which coordinately regulate phage lysogenic development. To obtain this protein, the cII gene was cloned into a plasmid vector carrying the strong, regulatable lambda phage promoter PL such that it was overproduced to levels approaching 5% of cellular protein. PMID- 6264322 TI - Novel leukaemogenic retroviruses isolated from cell line derived from spontaneous AKR tumour. PMID- 6264323 TI - Identification of E. coli uvrC protein. PMID- 6264324 TI - Positively activated transcription of lambda integrase gene initiates with UTP in vivo. PMID- 6264325 TI - Heterogeneous host DNA attached to the left end of mature bacteriophage Mu DNA. PMID- 6264326 TI - Modification of low virulent Newcastle disease virus infection in chickens infected with reticuloendotheliosis virus. AB - One-day-old SPF chicks were inoculated with reticuloendotheliosis virus (REV) which had been isolated from contaminated Marek's disease vaccine. Then they were subjected to super infection with the B1 or TCND strain of Newcastle disease virus (NDV) and examined for virus recovery, antibody response and the appearance of symptoms. Regardless of the time, from 0 to 8 weeks, of inoculation with the NDV-B1 strain after the REV infection, the antibody response was suppressed and the duration of the NDV recovery prolonged. Specific death preceded by severe respiratory or neural signs occurred more frequently to chicks inoculated with REV than to uninoculated controls after inoculation with the NDV-B1 strain in the neonatal stage or with the NDV-TCND strain at 5 weeks of age. PMID- 6264327 TI - Pathogenicity of Getah virus for mice. AB - The Sakai strain of Getah virus isolated from a feverish horse was examined for pathogenicity for mice. Its pathogenicity depended on the age of the host and the route of inoculation. Intracerebral inoculation caused death to mice less than 9 days old. It induced retarded growth, insufficient hair growth, paralysis, and sporadic death in mice 11 days old, but no symptoms in mice 13 days old. The virus multiplied rapidly and extensively in every tested organ, particularly in the muscular tissue, of the suckling mouse. It was also observed that the virus was transmitted horizontally among the litter-mates and vertically from the dam to her offspring via milk. PMID- 6264328 TI - Opiate receptors in the rabbit iris. AB - Evidence pointing to the presence of opiate receptors in the rabbit iris was obtained in an in vivo study of the effects on the pupil of the intraocular injection of morphine (10--100 micrograms) and D-Ala2-met-enkephalinamide (D-Ala E) (5--50 micrograms). Both opiates induced a significant dose-dependent decrease in pupillary size and an appreciable fluctuation of pupillary size. I.v. administration of naloxone (0.5 mg/kg) before or after injection of opiates prevented the miotic effect and the fluctuation of pupil size. The parallelism of the dose-response curves of opiates in the presence and absence of naloxone indicated competitive reversible antagonism. PMID- 6264329 TI - Direct and indirect actions of dopamine on tracheal smooth muscle. PMID- 6264331 TI - The blockade of Vmax of the atrioventricular action potential produced by the slow channel inhibitors verapamil and nifedipine. PMID- 6264330 TI - Adenosine receptor activation by adenine nucleotides requires conversion of the nucleotides to adenosine. AB - Adenine nucleotides cause adenosine receptor-mediated increases in cyclic AMP in the VA13 human fibroblast line. Levels of adenosine accumulated in the medium are insufficient to account for the responses to adenine nucleotides. Since rapid conversion of the nucleotides to adenosine by 5'-nucleotidase in the vicinity of the receptor might account for the responses, six experimental methods were developed to distinguish between "local conversion" and direct action of the nucleotides. Results of all six methods favored local conversion. (1)5' Nucleotidase inhibitors blocked the accumulations of cyclic AMP elicited by AMP, ADP, and ATP, but did not affect the response to adenosine. The most potent inhibitor of both conversion of AMP and response to AMP was alpha, beta-methylene ADP (APCP). (2) Adenosine deaminase blocked the responses to AMP, ADP, ATP, and adenosine-containing coenzymes. (3) Theophylline, a specific competitive adenosine antagonist, was an insurmountable inhibitor of the increases in cyclic AMP caused by AMP, ADP, and ATP. The insurmountability was presumably due to substrate saturation of the converting enzyme 5'-nucleotidase. (4) Although ADP and ATP had partial agonist-liked dose-response curves, they did not inhibit the response to adenosine. (5) Nine cell lines which responded to adenosine were tested for response to AMP. Cell lines with high levels of 5'-nucleotidase had large responses to AMP, those with intermediate levels of 5'-nucleotidase had large or intermediate responses to AMP, and those with low 5'-nucleotidase levels did not respond to AMP. (6) Inhibition of the uptake of labelled adenosine was used as an indicator of unlabelled adenosine concentrations near the cell membrane. Unlabelled AMP inhibited uptake nearly as effectively as unlabelled adenosine. APCP reversed the inhibition by AMP but not the inhibition by adenosine. The adenosine receptor is concluded to be an entity distinct from adenine nucleotide receptors. PMID- 6264332 TI - Decrease of some metabolic and physiologic effects of diazoxide by propranolol in rat. AB - Diazoxide significantly decreased the blood pressure and relaxed the uterine muscle in anaesthetized normotensive rats. A marked elevation of blood glucose followed the intravenous injection of diazoxide. The hyperglycemic and the uterine relaxing response could be significantly decreased by injection of propranolol prior to diazoxide. The hypotensive effect was not diminished by propranolol, however. In liver and uterus the content of cAMP was increased following diazoxide treatment in vivo. The rise in cAMP could be completely inhibited by propranolol, indicating a beta-receptor stimulation being the cause of the cAMP elevation. PMID- 6264333 TI - The inhibition by (+/-)-propranolol of the positive inotropic effects of (+/-) isoprenaline and (-)-noradrenaline. Competitive antagonism and saturable uptake. PMID- 6264334 TI - Increased phosphorylation in vitro of a cytosolic polypeptide resolved from denervated skeletal muscle. AB - The in vitro phosphorylation of a 40,400-dalton, cytosolic polypeptide from the soleus muscle of the rat is increased twofold within 24 hr after cutting the motor nerve fibers to this muscle. This involves an ATP-phosphotransferase reaction which we have reported to be inhibited by a specific cyclic AMP dependent protein kinase inhibitor. The phosphorylated polypeptide does not electrophoretically comigrate on SDS-polyacrylamide gels with the 38,000-dalton catalytic subunit of cyclic AMP-dependent protein kinase which is known to undergo a site-specific autophosphorylation in skeletal muscle. PMID- 6264335 TI - [Platelet suppressive drugs (author's transl)]. PMID- 6264336 TI - Preparation of 3H-[3-M3-His2]TRH as an improved ligand for TRH receptors. AB - [3H]-3-methyl-His2]thyrotropin releasing hormone ([3H]MeTRH) binds to sites in the sheep anterior pituitary gland which appear to be the same as those occupied by [3H]TRH and which can therefore be identified as TRH receptors. In competition experiments performed in parallel, both ligands gave the same number of binding sites, 15 pmol/g wet weight, and showed the same pharmacology for 19 TRH analogs ranging over more than 5 orders of magnitude in potency. The apparent dissociation constant of binding of [3H]MeTRH was about 3.5 nM compared to 29 nM for [3H]TRH. Kinetic experiments with [3H]MeTRH yielded a rate constant for association of 1.4 x 10(7) M-1 min-1 and rate constants for the biphasic dissociation of 5 x 10(-2) min-1 (fast phase) and 7 x 10(-3) min-1 (slow phase). Detailed methods are described for preparation of [3H]MeTRH by reduction of the dehydroproline precursor and its purification by ion exchange and antibody affinity chromatography. The major advantage of the new ligand is that its higher affinity of binding gives relatively less non-specific binding than is obtained with [3H]TRH, particularly in central nervous tissue. PMID- 6264337 TI - Effects of anticonvulsants on excitability and GABA sensitivity of cat dorsal root ganglion cells. PMID- 6264338 TI - An endogenous substance from porcine brain antagonizes the anticonvulsant effect of diazepam. PMID- 6264339 TI - An electrophysiological model of GABA-mediated neurotransmission. PMID- 6264340 TI - Chronic lithium administration alters the interaction between opiate antagonists and opiate receptors in vivo. PMID- 6264341 TI - Cannabinoid-induced enhancement and depression of cat monosynaptic reflexes. PMID- 6264342 TI - Hypertrophic neurofibrosis with onion bulb formation in an isolated element of the brachial plexus. PMID- 6264343 TI - Calcium-dependent regulation of the membrane potential and extrajunctional acetylcholine receptors of rat skeletal muscle. PMID- 6264344 TI - Maturation of sympathetic neurotransmission in the efferent pathway to the rat heart: ultrastructural analysis of ganglionic synaptogenesis in euthyroid and hyperthyroid neonates. PMID- 6264345 TI - The immunofluorescent localization of regulatory and catalytic subunits of cyclic AMP-dependent protein kinase in neuronal and glial cell types of the central nervous system. PMID- 6264346 TI - Experimental viral polymyositis: age dependency and immune responses to Ross River virus infection in mice. AB - Ross River virus (RRV) causes an age-dependent myositis in mice. Infected 4-week old mice develop no clinical signs, but 1-week-old mice develop weakness and myositis. Humoral and cell-mediated immune responses to RRV in the two age groups are comparable, and immunosuppression does not alter age-dependent resistance to clinical disease. Immunosuppression of 1-week-old mice protracts clinical signs and reduces muscle inflammation but does not alter muscle necrosis or regeneration. These studies suggest that immune responses do not determine age dependency of RRV myositis and that muscle necrosis results from direct viral lysis of muscle fibers. PMID- 6264347 TI - Role of inhibitory mechanisms in trigeminal neuralgia. AB - Segmental inhibition was elicited in the spinal trigeminal nucleus of cats by delivering a conditioning stimulus to the maxillary nerve 100 msec before the test stimulus. Carbamazepine, baclofen, and phenytoin markedly facilitated this segmental inhibition, as well as depressing the response to an unconditioned maxillary nerve stimulus. Phenobarbital, on the other hand, usually depressed the segmental inhibition. These results suggest that drugs that relieve trigeminal neuralgia both facilitate inhibitory mechanisms and depress excitatory mechanisms in the spinal trigeminal nucleus. The facilitation of inhibitory mechanisms appears to be at least as important as the depression of excitatory mechanisms and suggests that a failure of inhibitory mechanisms may play a significant role in the pathogenesis of trigeminal neuralgia. PMID- 6264348 TI - Sleep characteristics in infantile spasms. AB - Sleep staging was performed on 32 patients with infantile spasms. All patients demonstrated significantly less total sleep time and lower percentage of REM time than the expected normal values for age. Seventeen were treated with ACTH or prednisone. There was no increase in total sleep time in those who received hormone therapy, whether or not it was successful. However, the percentage of REM time increased significantly in patients who responded to therapy; this increase occurred concurrently with clinical and electroencephalographic improvement. There was no significant change in REM-sleep values in patients who did not respond. PMID- 6264349 TI - Disulfiram neuropathy. AB - In four patients, sensorimotor polyneuropathy developed during treatment with disulfiram. Each patient began to improve with the cessation of treatment. Clinical, electrophysiologic, and pathologic observations point to a potentially reversible and probably dose-related axonal polyneuropathy. PMID- 6264351 TI - Peripheral neuropathy in epileptic patients. AB - The prevalence of peripheral neuropathy in 186 epileptic patients was 16.7%. The neuropathy was characterized by stocking hypesthesia and reduced Achilles reflexes, and it occurred with all anticonvulsant agents. Electrophysiologic tests indicated slowing of peroneal and sural nerve conduction velocity and prolongation or absence of H reflexes and F responses. The prevalence of neuropathy was not greater in patients receiving phenytoin, and there was no relationship between clinical or electrical abnormalities and blood levels or duration of treatment for either phenytoin or phenobarbital. We did not find a specific relationship between phenytoin usage and peripheral neuropathy in epileptic patients. PMID- 6264350 TI - Familial spastic paraplegia, peroneal neuropathy, and crural hypopigmentation: a new neurocutaneous syndrome. AB - A neurocutaneous syndrome is described in which spastic paraplegia, peroneal neuropathy, and crural hypopigmentation are inherited in a dominant pattern. Spastic paraplegia becomes clinically apparent during adolescence or in childhood and progresses slowly throughout the adult years with a variability in severity of expression. Peroneal neuropathy is documented clinically and by slowing on nerve conduction studies. Pattern-reversal visual evoked potentials also yield a delayed response, but brainstem auditory evoked potentials and somatosensory evoked potentials in upper and lower extremities are normal. Crural hypopigmentation is present in each neurologically affected family member. Although the pattern may vary, a pretibial distribution predominates. The lower extremity abnormalities of the central and peripheral nervous system and neural crest cell derivatives may share a common relationship, but the abnormal visual evoked potentials suggest a more generalized involvement. This family may represent a transition form between familial spastic paraplegia and the spinocerebellar degenerations. PMID- 6264352 TI - [So-called post-herpetic neuralgia and phantom limb pain: therapeutic concepts needing review]. AB - After a brief review of the most recent findings on peripheral nerve nociception and deafferentation, the advisability of considering two so-called neuralgias - postherpetic neuralgia and phantom limb pain - in the more complex framework of deafferentation syndromes is examined together with the consequent need for a basic review of the therapeutic approaches pursued up to the present in the antalgic treatment of these two syndromes. PMID- 6264353 TI - [Results of radiotherapy of malignant epithelial tumors of the rhinopharynx. Study of 86 cases]. AB - The results of radiotherapy in 86 cases of malignant epithelial tumours of the rhinopharynx treated at the Radiology Department of Novara General Hospital are reported. Special attention is made to assessment of prognostic factors and the causes of therapeutic failure, insistence being laid on the need to make the utmost effort to improve irradiation technique. PMID- 6264355 TI - [Dietetic fiber in nutrition. Prophylactic and therapeutic activity and mechanism of action]. AB - The unabsorbable carbohydrates (dietary fibre) are contained in variable degrees in the vegetable foodstuffs. It seems by now clearly demonstrated that high residue diets (rich in unabsorbable carbohydrates) significantly prevents, although in different ways, some organic intestinal and metabolic diseases such as diabetes mellitus, obesity, hypercholesterolemia and atherosclerosis. PMID- 6264354 TI - [Hormone receptors in breast cancer]. AB - Following a review of studies on the presence of hormonal receptors in breast carcinoma, reference is made to personal experience with hormone treatment of 96 patients with breast cancer. On the basis of data obtained in clinical practice, it is concluded that in order to apply target hormone treatment, it is essential to carry out a full study of hormone receptors, not just as regards oestradiol, progesterone and prolactin but the others too (testosterone, glycocorticoids, insulin, thyroid and growth hormone). PMID- 6264356 TI - [Behavior of aldosterone and plasma renin activity after ACTH administration and insulin-induced hypoglycemia in patients with essential arterial hypertension]. AB - The response of plasma aldosterone (PA) and plasma renin activity (PRA) to ACTH stimulation (0.25 mg Tetracosactide infusion/10 h) and to insulin-induced hypoglycemia (0.1 U/kg b.w.) has been studied in 34 essential hypertensive (EH) patients. Corticotrophin stimulation increases significantly PA, the percent increase being higher in normal PRA EH patients than in controls but comparable to controls in low PRA EH patients. PRA shows a slight and transient elevation. A significant increase in PA is observed also during the insulin test, but the percent increase is lower than that under ACTH stimulation. The possibility that aldosterone is involved, under severe and frequent stress, in the genesis of essential hypertension is discussed. PMID- 6264357 TI - [Cytohistopathological correlations on material obtained by needle biopsy of the breast]. PMID- 6264358 TI - Umbilical metastasis from gynecologic malignancies: a primary carcinoma of the fallopian tube. PMID- 6264359 TI - Benign mixed tumor of the vagina. AB - A case of benign mixed tumor of the vagina is presented and the literature on this rare type of vaginal tumor is reviewed. The origin is likely to be the paravestibular glands, as the tumor is always located near the introitus. Follow up studies indicate benign biologic behavior, and simple excision is the treatment of choice. PMID- 6264360 TI - [Adenovirus keratoconjunctivitis and its treatment with the serum from convalescents]. PMID- 6264361 TI - Ultrastructural study of B-bodies in leukapheresed cells of patients with acute leukemia. AB - Peculiar inclusions, which we call B-bodies, have been observed in cells collected by leukapheresis from patients with acute leukemia. B-bodies, which often have virus-like features, were present in blast cells of 24 (44%)( of the 54 patients examined; in 16 out of 29 with acute myelogenous leukemia, 5 out of 16 with acute lymphoblastic leukemia, 2 out of 3 with undifferentiated leukemia, and 1 out of 2 with myelogenous leukemia in blastic transformation. The ultrastructure of these apparently polymorphic inclusions was always based on a system of of cytoplasmic channels containing dense, axial filaments. Patients with B-bodies were mostly women near menopause (70% of the positives). PMID- 6264362 TI - Thioacetamide-induced hepatocarcinoma in rat. AB - Out of 56 thioacetamide (TAA)-fed rats hepatocellular carcinoma were found in four instances after 300, 360, 450 and 495 days in the present experiment. Of the four tumours, two showed lung metastasis. The size of TAA-treated hepatocyte nucleoli increased greatly after several weeks of feeding. Two enzymes, succinate dehydrogenase and glucose-6-phosphatase were found in both cytoplasma and nucleoli of hepatocytes of which nucleolar localizations are quite new. In hepatocellular carcinoma, malignant cells lost glucose-6-phosphatase activity completely in cytoplasm and nucleoli though succinate dehydrogenase activity was present in these organelles. PMID- 6264363 TI - Ocular complications of juvenile angiofibroma. PMID- 6264364 TI - The role of viruses in the development of ocular tumors. AB - The role of viruses as a cause of human cancer has been investigated by a variety of techniques in recent years. While no definitive answer exists at present, several lines of evidence indicating a viral role in human tumors and reviewed. These include the well-documented role of viruses in causing animal tumors; evidence for an association of certain viruses with human tumors; and virally induced animal models of human tumors, melanoma, retinoblastoma, and ocular malignant melanoma. PMID- 6264365 TI - Thygeson's superficial punctate keratitis. AB - Thygeson's superficial keratitis is a chronic disease of the cornea characterized by focal epithelial lesions. We studied 45 cases of Thygeson's superficial punctate keratitis. Twenty-eight were male and 17 were female patients. The disease had been active in our patients from one month to 24 years. The clinical findings, course, outcome, and response to therapy were studied. Viral cultures and microscopic studies were performed on the corneal epithelial scrapings from ten cases. The average course of the disease was prolonged in patients who received topical steroid therapy. Subepithelial opacities were seen more frequently in patients who had received treatment with idoxuridine (IDU). PMID- 6264366 TI - Management of buccal space masses. AB - Lesions in the substance of the cheek--the buccal space--may present diagnostic and management difficulties. The buccal space, that potential fascia space lying within the bulk of the cheek, is anatomically described. While the history and physical characteristics of the buccal mass and selected radiographic and special procedures may suggest a specific cause, the diagnosis is often elusive and requires removal of the mass for histologic evaluation. The surgical approach to a mass in the cheek is governed by its location within the buccal space and by the index of suspicion of malignancy. The preauricular, submandibular approach is the authors' choice for most buccal space lesions. Five case reports are presented to illustrate features in the diagnosis and management of a buccal space mass. PMID- 6264368 TI - [Modifications of disulfiram and its metabolites in blood in alcoholic hepatopathy (author's transl)]. AB - In cirrhotic, steatosic and healthy subjects, the authors studied the metabolism of disulfiram (TETD) administrated orally (500 mg) 3 consecutive days. Carbon disulfide (CS2) and the whole TETD, diethyl dithiocarbamate (DDC) disulfides, were determined by a gas chromatographic method. The evolution of metabolites is similar in steatosic and healthy subjects. In cirrhotics the CS2, DDC and disulfides level increase within the 3 days. This phenomenon may be related with hepatic toxicity of TETD and with the persistence of disulfiram-alcohol reaction. The authors suggest to use low doses of disulfiram in cirrhotic. PMID- 6264367 TI - Immunologic detection of occult primary cancer of the head and neck. AB - Because antibody titers against Epstein-Barr virus (EBV) antigens often are elevated in patients with active undifferentiated and nonkeratinizing nasopharyngeal carcinoma, anti-EBV serologic tests have been applied as a diagnostic aid in patients who have metastatic lymphadenopathy in the neck without an obvious source. IN this study of 44 patients, the serologic testing procedure proved useful in identifying six patients with nasopharyngeal carcinoma that was initially occult but was eventually confirmed by biopsy. PMID- 6264369 TI - Study of a human heteroploid cell line cryptically infected by a murine oncornavirus. AB - This report concerns the establishment of a human cell line cryptically infected by a murine leukemia virus (MuLV). This cell line, named J112, is characterized by the presence of genetic viral information in a majority of cells as demonstrated by immunological and virological methods, and by the absence of detectable viral activity in the supernatant culture fluids. Nevertheless, electron microscopy demonstrated the presence of a small number of particles which have the morphology of immature type C particles. We discuss the importance of this experimental model in relationship with non-producing (NP) infections of human cells by oncogenic retroviruses. PMID- 6264371 TI - [Enzymatic reactions in the lungs of sheep during extracorporeal circulation]. PMID- 6264370 TI - [Comparative value of benzidine and alpha-naphthol for peroxidase reaction in leukemic cell (author's transl)]. AB - A comparative study of the benzidine technic and alpha-naphthol + pyronine technic for peroxidase is performed in blast cells of 27 patients. In the great majority of cases the benzidine technic is far more sensitive than the alpha naphthol technic. In regard to its low sensitivity this later technic is not relevant for classification of acute leukemia. PMID- 6264372 TI - [Pathomorphological changes in various internal organs of rats poisoned with lethal doses of thallium sulfate and treated with diethyldithiocarbamate, with special reference to kidney changes]. PMID- 6264373 TI - Lung catecholamines and cyclic nucleotides during perinatal development in the rat. Possible relationships with biochemical and morphological differentiation. AB - In this study, we investigated in parallel the evolution of endogenous catecholamine and cyclic nucleotide levels in lung tissue in the course of normal fetal development of the rat from day 17 of gestation to day 10 postpartum; the findings were correlated with the successive stages of lung differentiation. These were assessed morphologically by electron microscopy, and biochemically by measuring the levels of the main lung tissue phospholipids and studying their fatty acid composition. Dopamine levels were low and always remained under 5 ng/g of wet tissue. Nevertheless, slight rises were observed between days 17 and 19 of gestation (1.8 and 2.78 ng/g, respectively) and between days 21 of gestation and birth (2.56 and 4.25 ng/g, respectively). These changes were significant (P less than 0.05). Norepinephrine (NE) levels first decreased by about 50% between days 17 and 19 of gestation (7.34 and 3.88 ng/g, respectively), (P less than 0.01) and then rose sharply about 4 times until birth (17.24 +/- 3.90 ng/g), and more slowly from then on. On day 10 postpartum, the mean NE level was 34.31 +/- 3.28 ng/g. The levels of the two cyclic nucleotides [cyclic adenosine 3':5' monophosphate and cyclic guanosine 5'-monophosphate (cGMP)] were quite high on day 17 and remained so until day 19 (cAMP = 220 pmoles /g; cGMP = 20 pmoles/g). From day 19 until day 21, the levels of the two nucleotides decreased (cAMP = 140 pmoles/g; cGMP = 8 pmoles/g; P less than 0.05). During this period, the decrease in cGMP level was about twice that of cAMP. During the last day of gestation, the cAMP level was still decreasing, whereas cGMP was increasing. After birth, the levels of the two cyclic nucleotides rapidly increased to day 5. Between days 5 and 10 postpartum, no significant changes were observed in either cAMP or cGMP levels. The time course of the variations reported suggests that they are related to the maturation processes of lung assessed on the basis of morphological and biochemical criteria. On day 19 of gestation, when the first lamellar bodies appear, large changes occur in the evolution of NE and cyclic nucleotide levels, suggesting that these changes may be related to the onset of surfactant synthesis. On day 21 of gestation, the cAMP and cGMP ratio rises sharply; at the same time, the total phospholipid level is increased by 50%. At this stage, lamellar bodies are actively differentiating within type II pneumocytes and massively released into the fetal airways. The relationships between the variations of the studied biochemical parameters and the maturation processes of lung suggest that dopamine and NE could be involved in surfactant synthesis and release via their second messenger, the cyclic nucleotides. Further investigations are needed to elucidate the mechanisms regulating these changes. PMID- 6264375 TI - [Rehabilitation of infants and young children by neurophysiological methods]. PMID- 6264374 TI - The adrenomedullary and glucagon responses of hypopituitary children to insulin induced hypoglycemia. PMID- 6264376 TI - Glucose vs sucrose in oral rehydration solutions for infants and young children with rotavirus-associated diarrhea. AB - The use of oral rehydration solutions containing essential electrolytes and either glucose or sucrose of equal osmolality was compared in a double-blind sequential trial of 784 children with rotavirus-associated diarrhea treated at a center in rural Bangladesh. The oral fluid failure rate was 11.5% for the sucrose containing solution group and 7.3% for the glucose-containing group (P = NS). Vomiting was a significantly more common cause of failure for the group treated with sucrose-containing oral rehydration solution and was associated with an increased rate of intake of the sweeter sucrose-containing solution. The purging rate was not different for the two groups. The oral fluid failure rates for children in the most underweight category (less than 60% of expected weight for age) were not different from those for other groups, although, as assessed by purging rate and initial dehydration, the stool losses of members of this group constituted a greater proportion of their body weight. Glucose is the preferred carbohydrate for oral electrolyte solutions, although sucrose can be substituted with only minimum loss of efficacy. PMID- 6264377 TI - Effect of parathyroid hormone on vitamin D metabolism in osteopetrosis. AB - Indices of vitamin D metabolism were studied before and after infusion of bovine parathyroid hormone extract in three children with osteopetrosis. Basal serum concentrations of calcium, alkaline phosphatase, and 25-hydroxyvitamin D tended to be low. Serum immunoreactive parathyroid hormone levels were in the upper normal range in two patients. A marked increase in urinary cyclic adenosine 3':5' monophosphate (cAMP) in all patients was solely due to an increase in the nephrogenous cAMP. The basal concentration of 1,25-dihydroxyvitamin D was clearly more than the upper limit of normal range in all three patients and increased after parathyroid extract infusion in one patient. The basal serum levels of 24,25-dihydroxyvitamin D were within normal limits and tended to decrease after parathyroid extract infusion in two of the patients. Parathyroid hormone and 1,25 dihydroxyvitamin D act in concert to increase calcium resorption from bone, and the increased serum levels of both these factors may reflect lack, or unresponsiveness, of target cells in bone. PMID- 6264378 TI - Diploid-triploid mixoploidy: clinical and cytogenetic aspects. AB - A patient with 46, XY/69,XXY mixoploidy (a mixture of cell populations whose component cells differ in their chromosome numbers, irrespective of whether these numbers are euploid or aneuploid) who had some clinical manifestations of the Russell-Silver syndrome is reported. Triploidy results in a clinically recognizable lethal syndrome with hydatidiform placental changes, severe intrauterine growth deficiency, dysplastic cranial bones, eye defects, cleft lip and/or, palate malformed ears, micrognathia, syndactyly, genital anomalies and, rarely, spina bifida. Less severe are instances of diploid-triploid mixoploidy and patients are more likely to survive; one of these patients was detected at birth because of asymmetric growth deficiency with syndactyly. Cytogenetic and flow cytometric studies demonstrated absence of triploid cells in peripheral lymphocytes while varying proportions of triploid cells were found in fibroblast cultures derived from each limb. The triploid cell population disappeared with prolonged cell culture. Replication studies with 5-bromodeoxyuridine-DAPI fluorescence revealed two active X chromosomes, and marker chromosomes suggested a paternal origin for the extra haploid set. The following points are emphasized: (1) diploid-triploid mixoploidy can be suspected clinically; (2) the triploid cell population may not be detectable on examination of peripheral blood (3) the relative degree of asymmetry in the growth deficiency does not appear to relate to the proportion of triploid cells; and (4) both X chromosomes may remain active in the presence of an extra haploid set of chromosomes. PMID- 6264379 TI - Survival following myocarditis and myocardial calcification associated with infection by Coxsackie virus B-4. AB - A Coxsackie virus B-4 was isolated from a neonate with clinical sepsis and clinical evidence of myocardial dysfunction. Radiographs demonstrated the presence and subsequent resolution of myocardial calcification. Electrocardiograms showed a left bundle branch block, presumably caused by calcification in the corresponding segment of the bundle of His. This case demonstrates an unusual complication of neonatal Coxsackie virus B infection. PMID- 6264380 TI - [Gastroenteritis caused by rotavirus. An epidemiologic survey in Lyons. Diagnostic value of the ELISA method]. PMID- 6264382 TI - Inhibition of transient outward current by intracellular ion substitution unmasks slow inward calcium current in cardiac Purkinje fibers. PMID- 6264381 TI - Impairment of hormone-stimulated cardiac adenylate cyclase activity in the genetically obese (fa/fa) Zucker rat. AB - The age-related development of the capacity of the cardiac adenylate cyclase system to be stimulated with secretin, vasoactive intestinal peptide (VIP), glucagon, the beta-adrenergic agonist isoproterenol, Gpp(NH)p, and NaF was compared in obese (fa/fa) Zucker rats and their lean (FA/?) littermates. The obese (fa/fa) Zucker rats tested developed postweaning obesity associated with marked hypertriglyceridemia, mild hyperglycemia, and hyperinsulinism. At 4 weeks, there was already a 57% reduction in secretin-VIP-stimulated adenylate cyclase activity in fa/fa rats. At 12 weeks, the secretin-VIP-stimulation was reduced by 77%, and glucagon- and isoproterenol-stimulations by 16-21%. At 45 weeks, secretin-VIP-stimulation was reduced by 91%, glucagon- and isoproterenol stimulations by 34-42%, and Gpp(NH)p- and NaF-stimulations by 16-23%. The reductions of isoproterenol-, Gpp(NH)p-, and NaF-stimulations were totally or partially reversed in 30-week old fa/fa animals submitted for 5 weeks to severe food restriction that almost normalized the altered blood parameters. In sharp contrast, food restriction imposed a further decrease in secretin-VIP- and glucagon-stimulated adenylate cyclase activities. This pattern of impaired secretin-VIP-stimulated adenylate cyclase activity appeared limited to cardiac membranes in obese animals as the responses of liver, brain and anterior pituitary adenylate cyclase activities to secretin and/or VIP were unaltered. These results suggest that secretin-VIP receptors coupled to adenylate cyclase were rapidly and specifically altered in the heart of fa/fa Zucker rats. PMID- 6264384 TI - Apical K+ channels in frog skin (Rana temporaria): cation adsorption and voltage influence gating kinetics. AB - Open-close kinetics of fluctuating K+ channels in the apical frog skin membrane were studied with noise analysis of the K+ current (IK). The mucosa to serosa directed IK was obtained with serosal NaCl- and mucosal KCl-Ringer under voltage clamp conditions. Mucosal protons (pH greater than 4), several polyvalent metal ions, and choline shifted the plateaus (SO) of the Lorentzian component in the IK noise spectrum to higher, but the corner frequency (fc) to lower values. SO was lowered at pH less than 4, due to a K+-channel block by H+. Ca2+, Sr2+, H+ (pH greater than 4) and choline did not affect IK. A slight reduction of IK was seen with Mg2+, Mn2+, Co2+, Ni2+, Zn2+, Cu2+ and La3+. At pH greater than 4, the H+ induced shifts in SO an fc were almost abolished in solutions of high mucosal Ca2+ concentrations. Clamping the transepithelial potential difference to more positive values (with respect to the serosa) shifted the Lorentzian parameters SO and fc in the same way as the cations did. As with protons, mucosal Ca2+ interferred with the effect of voltage. The interference of cationic (probably fixed charge screening) and voltage effects suggests a common, more general mechanism of action, namely alterations in K+-channel fluctuation kinetics by changes in local electrical fields. On this basis, the rates for the open-close reaction of K+ channels and their mean lifetime were calculated. We found that e.g. increasing [Ca2+]O from 1-10 mM caused no change of the mean open time, but increased the mean time "closed" of the K+ channel by a factor of about 1.5. Other mucosal cations, as well as depolarizing clamp potentials are thought to have the same effect. PMID- 6264383 TI - Adrenalectomy and chemical sympathectomy by 6-hydroxydopamine. Effects on basal and stimulated insulin secretion. AB - Influences of the sympatho-adrenal system on basal and stimulated insulin secretion were studied in vivo in the conscious mouse and rat. In the mouse, adrenalectomy or chemical sympathectomy, induced by 6-hydroxydopamine, lowered basal insulin concentrations moderately. A marked depression of basal insulin concentration (about 50%) was seen after the combined treatment of chemical sympathectomy and adrenalectomy. In short-term experiments in mice, insulin secretion stimulated by glucose or the cholinergic agonist carbachol was enhanced after chemical sympathectomy and/or adrenalectomy, whereas insulin release induced by the synthetic octapeptide of cholecystokinin (CCK-8) was inhibited. The promoting influences on the insulin secretory response to carbachol displayed a rapid development whereas those to glucose developed more slowly. In contrast, the inhibiting effect on CCK-8 stimulated insulin release vanished with time. The insulin secretory response to the beta 2-adrenoceptor stimulator, terbutaline, was increased after chemical sympathectomy, unaffected by adrenalectomy, and decreased after chemical sympathectomy plus adrenalectomy. The glucose elimination rate after 6 weeks of chemical sympathectomy was increased in mice and decreased in rats. The insulin secretory response to glucose was enhanced in mice, whereas it tended to diminish in rats after long-term sympathectomy. In conclusion, the sympatho-adrenal system is involved in regulation of basal insulin concentrations in the mouse, and apparently is of great importance for stimulated insulin secretion; the influence being dependent on the nature of the secretagogue. PMID- 6264385 TI - Chloride reabsorption in the rabbit cortical thick ascending limb of the loop of Henle. A sodium dependent process. PMID- 6264386 TI - Cyclic AMP accumulation in the beta adrenergic mechanism of eccrine sweat secretion. AB - Tissue cyclic 3'5'-AMP (cAMP) concentrations were measured after stimulation of isolated monkey palm eccrine sweat glands with various stimulants of sweat secretion. The cellular cAMP levels increased curvilinearly with time of incubation to reach a steady state after 5 min of incubation with isoproterenol. Theophylline more than doubled the isoproterenol-induced cAMP accumulation, whereas theophylline alone increased the basal cAMP level to a minor extent. Phenylephrine failed to stimulate cAMP accumulation. There was no increase in the cAMP level after stimulation with methacholine. A calcium ionophore, A23187, also failed to stimulate cAMP accumulation. Since isoproterenol, theophylline (or isobutylmethylxanthine), and dibutyryl cAMP all induced eccrine sweat secretion in isolated, cannulated sweat glands to varying degrees in vitro, cAMP is probably involved in the beta adrenergic mechanism of sweat induction. The isoproterenol-induced cAMP accumulation was not inhibited by removal of Ca2+ from the incubation medium for as long as 30 min. The striking similarity between the eccrine sweat gland and the salivary glands in the roles that Ca2+ and cAMP play in stimulus secretion coupling indicates that the eccrine sweat gland will serve as another useful model system for the study of the mechanisms of exocrine secretion. PMID- 6264387 TI - Effects of parathyroid hormone and N6,O2'-dibutyryl cyclic AMP on Ca2+ transport across the rabbit distal nephron segments perfused in vitro. AB - Effects on Ca2+ transport of parathyroid hormone (PTH) and N6,O2'-dibutyryl adenosine 3',5'-cyclic monophosphate (DB-cAMP) were examined in the rabbit distal nephron segments including the cortical thick ascending limb of Henle's loop (CAL), the connecting tubule (CNT) and the cortical collecting tubule (CCT) by the in vitro perfusion technique. When PTH (10(-8) mol . l-1) was added to the bath, efflux of Ca2+ (pmol . mm-1 . min-1) was increased from 6.29 +/- 1.46 to 7.96 +/- 1.66 (P less than 0.02) in the CAL, and from 8.55 +/- 1.30 to 13.73 +/- 1.24 (P less than 0.001) in the CNT, respectively, without changes in influx of Ca2+. The effect of PTH on Ca2+ transport in the CAL, however, was abolished when phosphate concentration in the medium was reduced from 3.0 to 1.0 mmol . l-1. When DB-cAMP (10(-3) mol . l-1) was added to the bath, efflux of Ca2+ was also increased from 7.01 +/- 0.83 to 9.40 +/- 0.82 (P less than 0.05) in the CAL, and from 13.11 +/- 0.89 to 19.74 +/- 0.52 (P less than 0.005) in the CNT, respectively. By contrast, neither PTH nor DB-cAMP affected efflux of Ca2+ in the CCT. PTH did not affected the transepithelial voltage either in the CAL or in the CNT. But in the CNT, DB-cAMP decreased the voltage from -14.1 to -9.4 mV. The response of adenylate cyclase activity to PTH in the collagenase treated isolated nephron segments was also examined. Significant increases in adenylase cyclase activity were observed in the CAL as well as in the CNT with 10(-6) mol . l-1 PTH. These data indicate that PTH stimulates Ca2+ transport across the CNT probably via activation of the adenylate cyclase-cyclic AMP system. The hormone may also stimulate Ca2+ transport across the CAL in a special condition where plasma phosphate concentration is elevated. PMID- 6264390 TI - [Dietary fiber - theory and clinical aspects]. PMID- 6264388 TI - Neuromuscular Transmission in experimental autoimmune myasthenia gravis (EAMG). Quantitative ionophoresis and current fluctuation analysis at normal and myasthenic rat end-plates. AB - Chronic experimental autoimmune myasthenia gravis (EAMG) was induced in rats by immunization with acetylcholine receptor (AChR) purified from the electroplax of Torpedo californica. 35--40 days after immunization, serum anti-AChR antibody titers were about 40 nM. At this stage, electrophysiology was performed on isolated M. omohyoideus muscle-preparations from myasthenic and from normal (control) rats. For the study of the equilibrium interaction between acetylcholine (ACh) and AChR, dose-response curves were obtained by quantitative ionophoretic application of ACh to voltage-clamped end-plates. Analysis of dose response curves yielded the following parameters: maximum end-plate conductance per unit surface gmax (EAMG) = 10.3 +/- 1.1 nS/micrometer 2, gmax (normal) = 20.2 +/- 1.8 nS/micrometer 2; apparent dissociation constant K (EAMG) = 96 +/- 5 microM, K (normal) = 58 +/- 6 microM; Hill-coefficient nH (EAMG) = 2.3 +/- 0.1, nH (normal) = 2.3 +/- 0.1. Single channel properties were derived from an analysis of ACh-induced end-plate current noise: the mean single channel conductance was gamma (EAMG) = 20.1 +/- 2.2 pS, gamma (normal) = 27.6 +/- 1.8 pS and the mean channel life-time tau (EAMG) = 1.39 +/- 0.09 ms, tau (normal) = 1.32 +/- 0.08 ms (T = 22 degrees C). The electrophysiological data are interpreted as follows: (1) At myasthenic end-plates there is a 50--60% reduction of functioning AChR (decrease of gmax). A total number of about 2 x 10(6) (1 x 10(6)) channels per end-plate was calculated for control (myasthenic) rats. (2) The affinity of AChR for ACh is reduced and/or there is an impediment of the conformational change from the closed- to the open-channel configuration (increase of K). (3) Single channel properties are essentially unaffected. PMID- 6264389 TI - Cyclic-AMP mediated relaxation of chemically skinned fibers of smooth muscle. AB - Smooth muscle from guinea pig taenia coli was chemically skinned with Triton X 100 and stored in ATP-salt solution containing 50% glycerol at -20 degrees C. Fiber bundles were relaxed at Ca2+-concentrations below 10(-7) M, but contracted at 10(-6) M Ca2+. The isometric tension developed could be partly relaxed by the addition of c-AMP (in the presence of NaF), and it could also be inhibited following preincubation with the catalytic subunit of c-AMP dependent protein kinase. The inhibitory effect was much more pronounced at intermediate Ca2+ concentrations (e.g. 10(-6)) than at concentrations producing a maximum contraction, suggesting that Ca-sensitivity had been lowered. Sodium fluoride which was required to potentiate the c-AMP effects was found to have a slight relaxing effect per se. The c-AMP effect may be mediated through activation of cyclic AMP-dependent kinase, producing, phosphorylation of the myosin light chain kinase which, according to Adelstein et al. (1978), may result in a net dephosphorylation of the myosin light chains and a concomittant inhibition of the contractile response. PMID- 6264392 TI - Purified bacteriophage lambda O protein binds to four repeating sequences at the lambda replication origin. AB - The bacteriophage lambda O protein is needed for initiation of lambda DNA replication. Several lines of evidence suggest that initiation requires that this protein interacts with a specific sequence called ori (for origin) in lambda DNA. We have purified this protein to near homogeneity and studied the protection against nuclease cleavage of the origin DNA sequences. Our data demonstrate that the O protein binds within an interval of about 95 base pairs (bp), which contains four tandemly arranged 19bp repeating sequences, ATCCCTCAAAACGA (G)GG GAT(A). At a low concentration of O protein, the inner two repeats are primarily covered, while binding to the outer two repeats requires a high concentration of O protein. From the molecular size of O protein (32,000 daltons), and the internal symmetry in each 19bp repeat, we inferred that the O protein may bind in dimeric form, and that the 95bp region may be filled only when four such dimers have bound. This interaction is discussed in connection with the "activation" of the ori by O protein leading to initiation of DNA synthesis. PMID- 6264391 TI - An intron nucleotide sequence variant in a cloned beta +-thalassaemia globin gene. AB - A 7.5 kb Hsu I restriction fragment of genomic DNA containing a beta-globin gene has been isolated from a patient doubly heterozygous for beta + thalassaemia and a delta beta (Lepore globin fusion gene. This fragment must be derived from the chromosome carrying the beta +-thalassaemia determinant. The gross structure of the cloned gene plus flanking sequences is indistinguishable from that of a normal beta-globin gene. Within in 1606 base-pair transcribed region of the gene there is only one nucleotide difference from the normal beta-globin gene sequence. This is a G leads to A replacement 21 nucleotides upstream from the 3' terminus of the small intron. This nucleotide lies within a 10 base-pair sequence repeated in an inverted configuration near the 5' terminus of the small intron. The nucleotide replacement may result in a precursor mRNA less amenable to RNA splicing than its normal counterpart. PMID- 6264393 TI - The nucleotide sequence at the transcription termination site of ribosomal RNA in Drosophila melanogaster. AB - The sequence of 300 nucleotides surrounding the transcription termination site for ribosomal RNA in Drosophila melanogaster has been determined. The precise position of the RNA 3'-end was located by sizing rDNA fragments protected from S1 nuclease by hybridization with cytoplasmic 28S rRNA or with nuclear 38S pre-rRNA. Next, the sequence of the first 10 nucleotides at the 3'-end of 28S and 38S rRNA was determined directly. The results indicate the absence of 3'-terminal processing of the 38S pre-rRNA. The nucleotide sequence from a position 27 nucleotides upstream to 150 nucleotides downstream from the termination site was identical in three uninterrupted rRNA genes and one interrupted gene, except for a single base change in the spacer region of one clone. The terminal 100 nucleotides of Drosophila 28S rRNA have more than 60 per cent homology with the corresponding region of Xenopus 28S rRNA and yeast 26S rRNA. PMID- 6264394 TI - A T to A base substitution and small deletions in the conalbumin TATA box drastically decrease specific in vitro transcription. AB - We have previously shown that a T to G transversion at the second T of the conalbumin "TATA" box drastically decreases specific initiation of transcription by RNA polymerase B (1). We now report that a T to A transcription at the same nucleotide also drastically decreases transcription, suggesting that these mutations influence transcription mainly by altering nucleotide recognition rather than helix stability. Small deletions of 2, 3 and 4 nucleotides in the "TATA" box also drastically decrease specific initiation of transcription. PMID- 6264396 TI - Modification of the methylation pattern in the vicinity of the chicken globin genes in avian erythroblastosis virus transformed cells. AB - Having previously found a reduced transcription of globin genes and an abortive processing of the already transcribed globin pre-mRNA in Avian Erythroblastosis Virus (AEV) transformed cells (1), we compared the genomic DNA of these cells with that of normal chicken erythroblasts, using 32-P-labelled cDNA probes specific for the beta, alpha A and alpha D globin sequences. Restriction endonuclease digestion, electrophoresis of digests in agarose gels, Southern blotting and hybridization were carried out. Our results show that the overall genome organization is not disturbed in the immediate neighbourhood of the adult globin genes; the observed restriction fragments are identical for both DNAs after EcoRI, HindIII, BamHI and XbaI digestion, using the beta, alpha A and alpha D globin cDNA probes. However, we observe specific modifications at some methylation sites in the beta, beta-like and alpha D regions: after HpaII or MspI digestion in the alpha D region and after HhaI digestion in the beta and beta like region, heavier bands appear in the transformed cell DNA in addition to the ones observed in normal DNA. This implies that, at some specific sites, the transformed cell DNA is more methylated than the normal erythroblast DNA. The possible significance of this observation is discussed. PMID- 6264395 TI - Detection of the catalytic activities of DNA polymerases and their associated exonucleases following SDS-polyacrylamide gel electrophoresis. AB - A method is described to detect DNA polymerases and nucleases in homogeneous or crude enzyme preparations after electrophoresis in SDS-polyacrylamide gels(2) containing the appropriate template or substrate. DNA polymerases are electrophoresed in a gel containing gapped calf thymus DNA and after a renaturation treatment, the gel is incubated in a reaction mixture in which one deoxyribonucleoside triphosphate is [alpha-32P]-labelled. Incorporation of radioactivity into DNA is detected at the vicinity of the polymerase band by autoradiography. An associated nuclease activity can be measured after electrophoresis in a gel containing 32P-labelled gapped DNA, when nucleolytic digestion is seen as a clear band in the resulting autoradiogram. The gels can subsequently be stained with Coomassie blue to establish identical molecular weights of polymerase, nuclease and protein bands. Applications of this technique are discussed. PMID- 6264397 TI - Isolation and characterization of cloned human DNA fragments carrying reiterated sequences common to both autosomes and the X chromosome. AB - Several recombinants were identified and purified from a cloned library of human DNA by virtue of their homology to DNA from a mouse-human hybrid cell line containing a single human chromosome, the X, and their lack of homology to mouse DNA. Three recombinants were characterized in detail, and all were homologous to reiterated DNA from the human X chromosome. These recombinants also were homologous to reiterated sequences on one or more human autosomes and, therefore, were not X chromosome specific. The recombinant DNA fragments homologous to human reiterated X DNA were the same fragments homologous to human reiterated autosomal DNA. Digestion of genomic DNAs with several restriction enzymes revealed that the pattern of fragments homologous to one recombinant, lambda Hb2, was the same on autosomes as on the X chromosome, suggesting that the molecular organization of these elements on the X is not distinct from their organization on autosomes. PMID- 6264398 TI - Localization of the Tn5 transposase promoter using the cycling reaction of RNA polymerase. AB - RNA polymerase is known to undergo a cycling process during initiation of transcription in vitro in which large amounts of small oligonucleotides are released. We have used this cycling reaction to determine the 5' end of the RNA synthesized from the outer ends of the Tn5 inverted repeats. By analyzing the size of the radiolabeled oligonucleotides synthesized using different labeled nucleoside triphosphates and in reactions deficient for a particular nucleoside triphosphate, the partial 5' sequence was obtained. This sequence was correlated with the DNA sequence of the region and an unambiguous origin for the mRNA was determined. The start site for the RNA, which is located at 97 base pairs from the outer ends of the inverted repeats, was confirmed by digesting gamma-32 P-ATP labeled full length (run off) transcripts with ribonuclease T1. The resulting gamma-labeled T1 generated oligonucleotide corresponded to the predicted size determined using the cycling reaction. With the knowledge of the RNA start site, the probable translation start sites for the protein(s) known to be required for Tn5 transposition can be predicted. Possible implications of the DNA sequence with respect to the regulation of the transposase are also discussed. PMID- 6264399 TI - Reassociation rate limited displacement of DNA strands by branch migration. AB - Large branched DNA structures are constructed by two-step reassociation of separated complementary strands from restriction fragments of different lengths. The displacement of DNA strands initially annealed to longer complementary DNA sequences, a process mediated by branch migration, is very rapid and has thus far been followed only under conditions which are second order, DNA reassociation rate limiting. The average lifetime of branched DNA leading to displacement of 1.6 Kb strands is estimated to be less than 10 seconds under conditions of DNA reassociation, Tm-25 degrees C. Several DNA-binding drugs, including intercalating dyes, have been tested to determine their influence, if any, on the kinetics of DNA strand displacements by branch migration. Only actinomycin D was found to have significant effect under the conditions we have described. The kinetics of the strand displacement in the presence of low concentrations of actinomycin D remain second order and slower rate of strand displacement must be attributed to decreased rate of reassociation of DNA strands to form the branched intermediates. Consideration is given to the potential manipulation of DNA structures at site-directed branches and the limitations due to rapid strand displacements. The feasibility of constructing sufficiently large branched DNA regions to approach first order, branch migration rate limiting kinetics is also discussed. PMID- 6264400 TI - Nucleotide sequence and corresponding amino acid sequence of the gene for the major antigen of foot and mouth disease virus. AB - A segment of 1160 nucleotides of the FMDV genome has been sequenced using three overlapping fragments of cloned cDNA from FMDV strain O1K. This sequence contains the coding sequence for the viral capsid protein VP1 as shown by its homology to known and newly determined amino acid sequences from this man antigenic polypeptide of the FMDV virion. The structural gene for VP1 comprises 639 nucleotides which specify a sequence of 213 amino acids for the VP1 protein. The coding sequence is not flanked by start and stop codons which is consistent with the mode of biosynthesis of VP1 by post-translational processing of a polyprotein precursor. PMID- 6264401 TI - Properties of a DNA-dependent ATPase from rat mitochondria. AB - A DNA-dependent ATPase has been highly purified from rat liver mitochondria and characterized. The enzyme catalyzes the hydrolysis of ATP or dATP in the presence of single-stranded DNA cofactor and a divalent cation. The Km values for ATP and dATP are 0.15 mM and 0.35 mM, respectively. The enzyme activity is highly sensitive to N-ethylmaleimide. The sedimentation coefficient of the enzyme is 8.3 S in a glycerol gradient. From this and data on Sephadex G-200 gel filtration, the molecular weight of the native enzyme was calculated to be about 190,000. All the natural single-stranded DNAs tested were equally effective for the ATPase activity, but synthetic deoxyhomopolymer poly(dC) was found to be more effective than natural single-stranded DNAs. Synthetic and natural RNAs had no effect on the activity. PMID- 6264403 TI - Comparative examinations of 99mTc-DMS preparations obtained by labelling dimercaptosuccinate kits with different formulations. II. Comparison of chemical and biological characteristics of TcP-5 and MPI kits. AB - The chemical and biological characteristics of two dimercaptosuccinate kits were examined and compared: TcP-5 (produced at the Boris Kidric Institute - Vinca) in the freeze-dried form and MPI - the aqueous solution of tin dimercaptosuccinate. The radiochemical composition of the injection solutions was examined by various methods and the method of ascending paper chromatography in 50% aqueous methanol was found as satisfactory. Both preparations has similar compositions. Both preparations showed maximum renal concentrations 3-4 hrs after injection. Liver uptake of MPI was higher than that of TcP-5. The bench-life of both preparations was compared by measuring organ distribution. TcP-5 had a bench-life at least six hrs with a kidney/liver uptake ratio from 5.60 to 8.52, whereas MPI had a satisfactory bench-life of less than half an hour after labelling; thereafter, hepatic concentration rose and the kidney/liver uptake ratio dropped to 1.64. PMID- 6264402 TI - The construction of new vehicles for the cloning of transcription termination signals. AB - We have constructed new plasmids that can be used to clone transcription terminator containing DNA fragments between the first gene of the tryptophan (trp) operon and the tetracycline resistance (tet) gene. Both genes are under control of the trp promotor. Therefore the presence of a transcription termination signal on cloned fragments can be monitored by a decrease in expression of the tet gene. The plasmids contain cloning sites at different distances from the translation start signal. Consequently a cloned DNA fragment can be translated in the three possible reading frames, offering the opportunity to distinguish terminators from translation polarity (pseudo-terminators). The usefulness of the plasmids was shown by the cloning of the trp terminator and of a pseudo-terminator located in the trpB gene. PMID- 6264404 TI - [Scintigraphic diagnosis of experimentally induced pericarditis in dogs using 99mTc-labelled pyrophosphate (author's transl)]. AB - In the present paper the possibilities of scintigraphic diagnosis of experimental pericarditis are discussed. Pericarditis was induced by either talc or formaldehyde intrapericardially. In all animals the administration of talc as well as formaldehyde produced inflammatory changes which were more serious after formaldehyde. The scan of the talc pericarditis was carried out on the 7th day after operation and of the formaldehyde pericarditis on the 3rd, 7th or 14th days. No positive scintigraphic finding was made in any of the experimental animals, apart from a massive incorporation in the operation scars. The counting of radioactive impulses after the exstirpation of the tissue samples confirmed the scintigraphic findings. Statistical evaluation did not reveal any essential difference between the accumulation of the radiopharmaceutical into the pericarditis as well as into the pericardial bag in comparison with the control animals. Although our model does not exactly reflect the situation of patients suffering from pericarditis it may be assumed that pyrophosphate scintigraphy is not suitable for the diagnosis of acute pericarditis in clinical practice. PMID- 6264405 TI - Therapeutic diets: food for thought. PMID- 6264406 TI - Enkephalinase: selective inhibitors and partial characterization. AB - There are at least two types of enzymes in brain, endopeptidases and aminopeptidases, which metabolize enkephalins. Evidence is presented to suggest that enkephalinase, an endopeptidase cleaving at the Gly-Phe bond, is specific for the endogenous enkephalinergic system. Selective inhibitors are described for each enzyme. These are parachloromercuriphenylsulfonic acid and puromycin in the case of aminopeptidases and various enkephalin fragments in the case of enkephalinase. Some characteristics of the two types of enzymes are described. Enkephalinase has many properties in common with the well-characterized brain angiotensin-converting enzyme. These two enzymes, however, behaved differently when tested for chloride dependence, for activity in several buffers and for susceptibility to specific inhibitors. PMID- 6264408 TI - A neuroheptapeptide influence on cognitive functioning in the elderly. AB - The heptapeptide core common to melanocyte-stimulating hormone (MSH) and adrenocorticotropin (ACTH) was administered as a single subcutaneous dose of 30 mg to 13 elderly human subjects (9 men, 4 women) in a double-blind, cross-over design. Significant improvement was found in the Benton Visual Retention Test after MSH/ACTH 4--10 as compared with administration of saline. This appeared to be greater in men than women. No side effects or laboratory abnormalities were observed. The behavioral results are consistent with our earlier findings in men and rats of improved visual attention after administration of MSH and extend them to the elderly population. PMID- 6264407 TI - CCK-octapeptide injected in CSF decreases meal size and daily food intake in sheep. AB - Cholecystokinin octapeptide (CCK-OP) is a potent and specific suppressor of feeding when administered as a continuous lateral cerebral ventricular injection in fasted sheep, and we have proposed that endogenous CCK-OP in the brain is released during meals and acts to terminate feeding. In previous studies, however, only relatively short-term effects of CCK-OP on feeding were examined. In the first experiment of the present series sheep were adapted to a 6-hr feeding period per day. CCK-OP injected continuously for 6 hr into the lateral ventricles reduced feeding during the entire feeding period (809 +/- 72 g, sham; 695 +/- 71 g, carrier; 505 +/- 69 g, CCK-OP; p less than 0.05). In addition mean feed intake for the two days (injection + first post injection day) was significantly reduced by CCK-OP; thus with CCK-OP, sheep did not compensate by the day after injection for the decreased feed intake on injection day. In a second experiment CCK-OP was injected into the lateral ventricles only during four consecutive 15 min meals 2 hours apart. With a dose of 0.159 pmoles/min CCK OP, size of the second meal was reduced, but with 0.638 pmoles/min CCK-OP feeding during each of the first two meals was reduced and cumulative intake for the four meals was decreased. These results indicate that CCK-OP administered centrally can have long-term effects on feeding, and under appropriate conditions, could result in negative energy balance. PMID- 6264409 TI - ACTH accelerates recovery of neuromuscular function following crushing of peripheral nerve. AB - Adrenocorticotropin (ACTH)-treated adrenalectomized rats subjected to crush denervation recover sensation and functional movement sooner than saline-treated rats. Axonal regeneration is accelerated, the number of large endplates and the frequency of preterminal branching are increased. ACTH has no effect on either intact or denervated muscles. The ameliorative action of ACTH during regeneration is apparently neurogenic and independent of corticoids. PMID- 6264411 TI - Feeding and selection of saccharin after injections of bombesin, LiCl, and NaCl. AB - Rats injected with bombesin of LiCl showed similar suppression of food deprivation-induced liquid diet intake, but only rats receiving LiCl avoided water-deprivation-induced consumption of a novel saccharin solution paired with injection. The data demonstrate that bombesin reduces feeding but does not induce conditioned aversion, and suggest that bombesin does not act to suppress food intake by production of gastrointestinal malaise. PMID- 6264410 TI - Neuropeptides in the gut: quantification and characterization of cholecystokinin octapeptide-, bombesin- and vasoactive intestinal polypeptide-like immunoreactivities in the myenteric plexus of the guinea-pig small institute. AB - The localization of CCK8-, bombesin- and VIP-like immunoreactivities in the myenteric plexus of the guinea pig small intestine has been studied by radioimmunoassay of extracts of longitudinal muscle strips obtained with and without adherent myenteric plexus; concentrations were compared with those in other regions of the gut. In innervated strips of longitudinal muscle of ileum there was approximately 14 pmol/g CCK8-, 32 pmol/g bombesin- and 135 pmol/g VIP like immunoreactivity; concentrations were reduced by over 70% in denervated strips. Gel filtration and ion exchange chromatography indicated that over 80% of CCK immunoreactivity was due to CCK8; no evidence was found of significant amounts of smaller COOH-terminal fragments. Bombesin immunoreactivity occurred in two forms, the major one resembling the amphibian tetradecapeptide in its elution from gel filtration columns. Immunoreactive VIP differed markedly from porcine VIP in immunochemical and chromatographic properties; the data suggest that guinea pig VIP is less basic than porcine VIP and that the two peptides differ in structure in their NH2-terminal regions. Some functional implications of these findings are discussed. PMID- 6264412 TI - Tobacco mosaic virus-enkephalin conjugates: potentiation of opioid activity. AB - Covalent tobacco mosaic virus-enkephalin analogue conjugates containing between 5 and 450 agonist molecules attached through their C-terminal amino acids were prepared and assayed in pharmacological and binding assays that distinguish between mu- and delta-receptors. Increases in peptide- and receptor-specific potency and affinity were observed with a certain preference of mu- over delta receptors. The results may become important for mapping receptors or for isolating opiate receptor-bearing membrane vesicles. PMID- 6264413 TI - [Computerized tomography of the head (author's transl)]. PMID- 6264414 TI - [Selected pneumotropic viruses in chronic respiratory tract diseases]. PMID- 6264415 TI - [Dietary fiber as a natural food component preventing the development of digestive tract diseases and arteriosclerosis]. PMID- 6264416 TI - [Icteric form of cytomegalic inclusion disease in patients on long-term dialysis]. PMID- 6264417 TI - [Histochemical studies in experimental acute pancreatitis]. PMID- 6264418 TI - [Partial denture using Milling technics. 11. After care]. PMID- 6264419 TI - [Quantitative determination of the activity of various enzymes in the blood cells of patients with tuberculosis]. PMID- 6264420 TI - [Collagen peptidase activity in pulmonary tuberculosis]. PMID- 6264421 TI - Renal allograft function and cytomegaly. AB - A retrospective study in 20 seronegative and 61 seropositive (complement fixation) first cadaver donor graft recipients brought evidence that in cytomegaly, not the infection alone, but curtailment of azathioprine shortly after transplantation (or summation of both) may result in rejection and impaired graft survival. Preliminary data (accumulation of 125I-labelled fibrinogen in two and morphology of the graft in two other patients) showed that depression of graft function in cytomegaly is not necessarily due to rejection. PMID- 6264422 TI - Early diagnosis of cytomegalovirus infection in renal transplantation. PMID- 6264423 TI - BK papovavirus immune complexes in glomerulonephritis. AB - Kidney biopsies from 98 patients were studied for BK virus (BKV) antigens by indirect immunofluorescence. Intense fluorescent staining was observed in 11/12 cases of lupus nephritis, 11/12 cases of membranous nephropathy, 21/23 cases of IgA mesangial glomerulonephritis, 3/4 cases of membrano-proliferative Glomerulonephritis and 5/12 cases of exudative glomerulonephritis. Antisera of different viruses did not react with any kidney sample. Deposition of BKV was strictly related to the presence of immunoglobulins in renal glomeruli. The specificity of reaction for antigens related to BKV was demonstrated by absorption of sera with different substances and BKV. Absorption of rabbit anti BKV serum with human immunoglobulins completely abolished glomerular fluorescence. We conclude that the fluorescence obtained in kidney biopsies by staining with anti-BKV serum was a false positive reaction dependent on common antigenic determinants present in BKV capsid proteins and human immunoglobulins. PMID- 6264424 TI - Human glomerulonephritis and persistent non-polio enterovirus infection. AB - In a prospective work, we have studied the non-polio enterovirus (NPEV) excretion in spot urine and stools by four appropriate cell cultures, in four different groups: 20 exposed controls (GI), 88 patients with renal biopsy 'proven GN' (GII), 38 cases with 'proven nonGN' (GIII), and 9 with 'probable nonGN' (GIV). The positive excretion in stools and/or urine is respectively 0 and 5% in Group I, 14 and 33% in Group II, 6 and 19% in Group III, and 13 and 22% in Group IV. Viruria, the consequence of a viraemia, is therefore associated with 'proven GN' (p less than 0.05). In the majority of patients with positive NPEV excretion, we have made an additional but similar study, 3-12 months later. Persistent excretion was confirmed in 22/30 cases in Group II (73%) versus 0/8 in Group III IV (p less than 0.001). These data concerned patients with membranoproliferative GN [5], membranous GN [6], mesangial IgA GN [6], endocapillary GN [2] or minimal lesions [3]. Thus we have demonstrated a significant relation between persistent NPEV urine/stools excretion and the occurrence of active GN in humans. Such persistent viral infections may represent the cause of some GN, probably mediated by an immune complex mechanism with viral antigens. PMID- 6264425 TI - Identification of a promoter component involved in positioning the 5' termini of simian virus 40 early mRNAs. AB - The 5' termini of the principal early mRNAs produced in cells transformed by wild type simian virus 40 lie 21-25 nucleotides downstream from an A-T-T-T-A-T sequence on the DNA template. The 5' termini of early mRNAs produced by five origin-defective mutants containing deletions downstream from the A-T-T-T-A-T sequence and one viable mutant dl892 with a deletion starting 15 nucleotides upstream from this sequence were determined by a method involving synthesis, separation, and determination of the sequences of DNAs complementary to 5' termini. Mutant dl892 produced early mRNAs with the same principal 5' termini as wild-type virus; the origin-defective mutants produced mRNAs with principal 5' termini shifted downstream by a distance equivalent to the length of the deleted DNA segment. These data suggest that a DNA sequence of 29 nucleotides, which includes the A-T-T-T-A-T sequence, contains a component(s) of a promoter for early transcription. This component functions in positioning the 5' ends of the principal early mRNAs 21-25 nucleotides downstream from the A-T-T-T-A-T sequence and acts independently of these downstream sequences. PMID- 6264426 TI - Nucleotide sequence of cloned unintegrated avian sarcoma virus DNA: viral DNA contains direct and inverted repeats similar to those in transposable elements. AB - We have determined the nucleotide sequence of portions of two circular avian sarcoma virus (ASV) DNA molecules cloned in a prokaryotic host--vector system. The region whose sequence was determined represents the circle junction site- i.e., the site at which the ends of the unintegrated linear DNA are fused to form circular DNA. The sequence from one cloned molecule, SRA-2, shows that the circle junction site is the center of a 330-base-pair (bp) tandem direct repeat, presumably representing the fusion of the long terminal repeat (LTR) units known to be present at the ends of the linear DNA. The circle junction site is also the center of a 15-bp imperfect inverted repeat, which thus appears at the boundaries of the LTR. The structure of ASV DNA--unique coding region flanked by a direct repeat that is, in turn, terminated with a short inverted repeat--is very similar to the structure of certain transposable elements. Several features of the sequence imply that circularization to form the SRA-2 molecule occurred without loss of information from the linear DNA precursor. Circularization of another cloned viral DNA molecule, SRA-1, probably occurred by a different mechanism. The circle junction site of the SRA-1 molecule has a 63-bp deletion, which may have arisen by a mechanism that is analogous to the integration of viral DNA into the host genome. Flanking one side of the tandem direct repeat is the binding site for tRNATrp, the previously described primer for synthesis of the first strand of viral DNA. The other side of the direct repeat is flanked by a polypurine tract, A-G-G-G-A-G-G-G-G-G-A, which may represent the position of the primer for synthesis of the second strand of viral DNA. An A+T-rich region, upstream from the RNA capping site, and the sequence A-A-T-A-A-A are present within the direct repeat sequence. These sequences may serve as a promoter site and poly(A) addition signal, respectively, as proposed for other eukaryotic transcription units. PMID- 6264427 TI - Expression of simian virus 40-rat preproinsulin recombinants in monkey kidney cells: use of preproinsulin RNA processing signals. AB - The complete rat preproinsulin gene I was cloned into a simian virus 30 (SV 40) vector. Most of the late region of the viral vector, including the SV40 intervening sequences (introns) and all of the major splice junctions, was deleted and replaced by the entire rat insulin gene. The recombinant molecules and a temperature-sensitive helper virus (tsA28) were inoculated into monkey kidney cultures. The formation of stable transcripts of the insulin insert was as efficient as the production of late SV40 mRNA. Analysis of these transcripts indicated that the rat preproinsulin gene nucleotide signals involved in RNA splicing and poly(A) addition were used. Examination of the 5' ends of the mRNAs showed several classes, one of which was the same size as the authentic rat insulinoma mRNA. This suggests that a portion of the transcripts may be initiated or processed faithfully, or both, at their 5' ends within rat insulin sequences. Significant quantities of a protein identified as rat proinsulin were synthesized. Detection of most of the proinsulin in the tissue culture medium suggests that this protein was secreted. PMID- 6264428 TI - DNase I hypersensitive sites in Drosophila chromatin occur at the 5' ends of regions of transcription. AB - By using a map of the unique region of DNA encoding the fur small heat-shock proteins of Drosophila melanogaster (hsp 22, hsp 23, hsp 26, and hsp 28), and a simple mapping technique, the positions of the DNase I hypersensitive sites of chromatin in the vicinity of these genes have now been determined. The major chromatin-specific sites occur at the 5' ends of each of the four heat-shock protein genes in embryo nuclei. These genes are not active in the nuclei analyzed but can be quickly induced in these cells by the heat-shock stimulus. The chromatin structure indicated by DNase I hypersensitivity may be a necessary factor in the general mechanism of gene activation. PMID- 6264429 TI - Location, function, and nucleotide sequence of a promoter for bacteriophage T3 RNA polymerase. AB - The major promoters for bacteriophage T3 RNA polymerase on the T3 genome have been mapped by DNA.RNA filter hybridization. One promoter is located in a 300 base-pair Hpa I restriction fragment near the genetic "left" end of T3 DNA. The sequence in the vicinity of the major initiation site of transcription in this region has been determined. A part of the (-)strand sequence is 5' T-A-T-T-T-A-C C-C-T-C-A-C-T-A-A-A-G-+1 G-G-A-A-U 3'. Comparison of this sequence with the prototype 23-base-pair promoter sequence for bacteriophage T7 RNA polymerase shows a striking pattern of homology and divergence. Between positions -9 and +4, the sequences are virtually identical, whereas between positions -17 and -10, the sequences are quite different. It is postulated that these sequence subsets may perform different functions in transcription initiation by the phage RNA polymerases. PMID- 6264430 TI - Flow of information in the light-triggered cyclic nucleotide cascade of vision. AB - Photolyzed rhodopsin catalyzes the exchange of GTP for FDP bound to a protein in retinal rod outer segments. We previously proposed that the GTP complex of this protein regulates the cyclic GMP phosphodiesterase and that it may be the first amplified intermediate in visual excitation [Fung, B. K.-K. & Stryer, L. (1980) Proc. Natl. Acad. Sci. USA 77, 2500-2504]. We report here the identification and characterization of transducin, a regulatory protein consisting of three kinds of polypeptide chains: T alpha (39 kilodaltons), T beta (36 kilodaltons), and T gamma (approximately 10 kilodaltons). Reconstituted membranes containing transducin and rhodopsin but no phosphodiesterase exhibit GTPase activity and amplified binding of guanosine 5'[beta, gamma-imido]triphosphate (p[NH]ppG), a nonhydrolyzable analog of GTP, on illumination. A single photolyzed rhodopsin molecule led to the uptake of p[NH]ppG by 71 molecules of transducin. High pressure liquid chromatography showed that the binding site for GTP is on the alpha subunit of transducin. The isolation of the complex of ;[NH]ppG with T alpha enabled us to determine whether this species is the activator of the phosphodiesterase. We found that phosphodiesterase on unilluminated disc membranes can indeed be fully activated by addition of T alpha containing bound p[NH]ppG. These findings strongly suggest that transducin is the first amplified information-carrying intermediate in the cyclic nucleotide cascade of vision. PMID- 6264431 TI - Diphtheria toxin forms transmembrane channels in planar lipid bilayers. AB - When exposed to a lipid bilayer, diphtheria toxin binds to it and forms transmembrane, voltage-dependent, anion-selective channels. The mean (+/- SD) conductance of these channels in asolectin membranes is 6.2 +/- 0.7 pmho (pS) in 0.2 M NaCl and 20 +/- 2 pmho in 1.0 M NaCl. The rate of channel formation depends on the pH in the toxin-containing compartment; it is very low at pH greater than 5.0 and increases abruptly as the pH decreases from 4.9 to 4.0. Binding of toxin to the membrane is also pH dependent, being unmeasurable at pH 7 and increasing monotonically with decreasing pH. The rate of channel formation depends upon membrane potential as well; channels form only at negative potentials. These channels are permanent in the time scale of the experiments (about 1 hr). The membrane conductance caused by the channels is also voltage dependent, being constant at positive potentials and decreasing at negative potentials. Hence, the current-voltage curve is linear at positive potentials and sublinear at negative potentials. The conditions necessary for insertion of toxin into the bilayer and formation of channels are similar to those that prevail inside the lysosome. Thus, these results lend credence to the idea that toxin enters the cytoplasm from the lysosomal compartment. PMID- 6264432 TI - Restoration of glucagon responsiveness in spontaneously transformed rat hepatocytes (RL-PR-C) by fusion with normal progenitor cells and rat liver plasma membranes. AB - Spontaneously transformed RL-PR-C rat hepatocytes, unlike their normal differentiated progenitor cells, are insensitive to glucagon, although seemingly possessing large numbers of glucagon receptors and although retaining guanyl nucleotide regulatory protein-adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] system that responds to catecholamines, cholera toxin, and fluoride ions. Biochemical fusions between normal RL-PR-C hepatocytes or purified rat liver plasma membranes (whose adenylate cyclases were previously irreversibly inactivated with N-ethylmaleimide) with spontaneously transformed hepatocytes produced hybrids whose basal and fluoride-stimulated adenylate cyclase activities reflected those of the parental transformed cells but that now responded to glucagon. Using cholera toxin-catalyzed ADP-riboxylation of transformed hepatocytes to mark their guanyl nucleotide regulatory protein, fusiong such cells with N-ethylmaleimide-treated normal hepatocytes, and examining glucagon stimulation of adenylate cyclase activity in fusion hybrids produced results suggesting that the regulatory protein of the transformed cells is functionally normal. In fusion experiments between N-ethylmaleimide-treated hepatocytes and igeon erythrocytes, we found that normal, but not transformed, hepatocytes were effective in conferring glucagon sensitivity upon erythrocytes. Glucagon binding data revealed that, whereas normal RL-PR-C hepatocytes have two independent classes of binding sites, one of higher and the other of lower affinity, transformed cells possess only the low-affinity receptors. From these and previous observations, it is possible to conclude that the insensitivity of spontaneously transformed RL-PR-C hepatocytes to glucagon is due to the loss, during the transformation process, of the high-affinity glucagon receptor. PMID- 6264433 TI - Mechanism of mRNA capping by vaccinia virus guanylyltransferase: characterization of an enzyme--guanylate intermediate. AB - Vaccinia virus RNA guanylyltransferase catalyzes the transfer of GMP from GTP to the 5'-triphosphate or diphosphate terminus of RNA to generate the cap structure G(5')ppp(5')N-. The guanylylation reaction consists of a series of at least two partial reactions: (i) GTP + E in equilibrium E-pG + PPi, (ii) E-pG + (p)ppNpNpN- leads to GpppNpNpN- + E. Inthe first of these, GTP reacts with capping enzyme in the absence of an RNA acceptor to form a covalent enzyme-guanylate intermediate. The GMP is linked to the Mr 95,000 subunit of the capping enzyme via a phosphoamide bond, as judged by the acid-labile, alkali-stable nature of the bond and by the susceptibility of the linkage to cleavage by hydroxylamine at pH 4.75. The isolated enzyme-guanylate complex is able to transfer the guanylate moiety to triphosphate-terminated poly(A) to yield the 5' cap structure GpppA or to pyrophosphate to regenerate GTP. Both partial reactions of transguanylylation require a divalent cation. PMID- 6264436 TI - Water structure-dependent charge transport in proteins. AB - Dielectric and conductivity measurements are reported for bovine serum albumin as a function of hydration. Strong evidence is found for the existence of mobile charges whose short- and long-range hopping motion strongly depends on the physical state of the protein-bound water. These charges are considered to be protons. Insights into the nature of the electrical properties of protein methylglyoxal complexes are provided, and the possibilities for correlated proton electron motions are outlined. PMID- 6264435 TI - Cytochrome oxidase (a3) heme and copper observed by low-temperature Fourier transform infrared spectroscopy of the CO complex. AB - Carbon monoxide bound to iron or copper in substrate-reduced mitochondrial cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1) from beef heart has been used to explore the structural interaction of the a3 heme copper pocket at 15 K and 80 K in the dark and in the presence of visible light. The vibrational absorptions of CO measured by a Fourier transform infrared interferometer occur in the dark at 1963 cm-1, with small absorptions near 1952 cm-1, and are due to a3 heme--CO complexes. These disappear in strong visible light and are replaced by a major absorption at 2062 cm-1 and a minor one at 2043 cm-1 due to Cu--CO. Relaxation in the dark is rapid and quantitative at 210 K, but becomes negligible below 140 K. The multiple absorptions indicate structural heterogeneity of cytochrome oxidase in mitochondria. The Cu--CO absorptions (vCO) are similar to those in hemocyanin--CO complexes from molluscs (vCO - 2062 cm-1) and crustaceans (vCO = 2043 cm-1). The 2062 cm-1 Cu--CO absorption of cytochrome oxidase is split into two bands at 15 K. Analysis of spectral data suggest the presence of a very nonpolar heme--Cu pocket in which the heme-CO complex is highly ordered, but in which the Cu--CO complex is much more flexible, especially above 80 K. A function for these structures in oxygen reduction is proposed. PMID- 6264434 TI - Biological reactivity of hypochlorous acid: implications for microbicidal mechanisms of leukocyte myeloperoxidase. AB - Oxidative degradation of biological substrates by hypochlorous acid has been examined under reaction conditions similar to those found in active phagosomes. Iron sulfur proteins are bleached extremely rapidly, followed in decreasing order by beta-carotene, nucleotides, porphyrins, and heme proteins. Enzymes containing essential cysteine molecules are inactivated with an effectiveness that roughly parallels the nucleophilic reactivities of their sulfhydryl groups. Other compounds, including glucosamines, quinones, riboflavin, and, except for N chlorination, phospholipids, are unreactive. Rapid irreversible oxidation of cytochromes, adenine nucleotides, and carotene pigments occurs when bacterial cells are exposed to exogenous hypochlorous acid; with Escherichia coli, titrimetric oxidation of cytochrome was found to coincide with loss of aerobic respiration. The occurrence of these cellular reactions implicates hypochlorous acid as a primary microbicide in myeloperoxidase-containing leukocytes; the reactivity patterns observed are consistent with the view that bactericidal action results primarily from loss of energy-linked respiration due to destruction of cellular electron transport chains and the adenine nucleotide pool. PMID- 6264437 TI - Neoplastic transformation of chimpanzee cells induced by adenovirus type 12- simian virus 40 hybrid virus. AB - The adenovirus 12--simian virus 40 hybrid virus produced neoplastic transformation of chimpanzee skin fibroblasts in vitro. The transformed fibroblasts showed morphological alteration and became permanent lines. The transformed cells contained both adenovirus 12 and simian virus 40 large tumor antigens and were virus producers. However at passage 9, one line (WES) was found to be a nonproducer, producing neither infectious virus nor virus-specific antigen detectable by the complement fixation test. Virus particles were not detected nor could infectious hybrid virus be rescued from this line by cocultivation with Vero cells. The transformed cells formed large cell aggregates and grew in liquid growth medium above an agar base, formed colonies in soft agar, and grew to high saturation densities; the normal chimpanzee skin fibroblasts did not. One transformed WES line produced tumors when transplanted subcutaneously into newborn nude mice, thus providing an important tool for studying tumor immunity in the chimpanzee. PMID- 6264438 TI - Secretory granules of an anterior pituitary cell line, AtT-20, contain only mature forms of corticotropin and beta-lipotropin. AB - The pituitary cell line, AtT-20, synthesizes the precursor to corticotropin (adrenocorticotropic hormone; ACTH) and beta-endorphin and correctly glycosylates and cleaves it to make the mature forms of the hormones before they are secreted. This cell line was used to study the intracellular transport, packaging, and secretion of these hormones. Secretory granules from the cells were isolated by homogenization and differential centrifugation and isopycnic sedimentation on a 2H2O-Ficoll gradient to give a preparation having a specific activity of 90micrograms ACTH per mg of protein, which is 30- to 90-fold greater than that of whole cells. The granules have density characteristics and a sedimentation coefficient that are appropriate for spheres of 1000 A radius. They contain all of the fragments of the initial ACTH/endorphin precursor but almost undetectable amounts of the intact precursor. The fragments constitute about 50% of the protein in the secretory granule fraction and, from density measurements, we estimate that they are present in approximately 60,000 copies per vesicle. The cell line secretory granules appear, therefore, to be similar to mature secretory granules in normal differentiated tissues. ACTH first appears in the secretory granule at 30-45 min after synthesis. Cleavage of the precursor to mature ACTH occurs at about the same time in the whole cell. Therefore, proteolysis of the prohormone to ACTH and to beta-lipotropin is a metabolic event that can be correlated with the packaging of the hormone into a mature secretory granule. Cleavage of beta-lipotropin to beta-endorphin occurs later, probably in the secretory granule. PMID- 6264439 TI - Embryonic erythroid differentiation in the human leukemic cell line K562. AB - K562 human leukemia cells synthesize embryonic hemoglobins after culture in the presence of hemin. We have rigorously identified these hemoglobins by globin chain analysis and peptide mapping. No adult hemoglobin could be detected, and beta-globin synthesis was less than 2 ppm of total protein synthesis. Persistent embryonic globin gene expression is known to occur as a consequence of globin gene deletions. However, restriction endonuclease mapping showed that the globin gene complexes in K562 cells are indistinguishable from normal. Hemin increased the rate of embryonic globin synthesis. The pattern of hemoglobin synthesis proved to be stable when cells from different laboratories were compared. One line, however, synthesized large amounts of Hb X and very little Hb Portland in response to hemin. Hb X has been previously detected in human embryos; we show here that it has the composition epsilon 2 gamma 2 and is diagnostic of imbalanced chain synthesis or "zeta thalassemia." We have identified several agents that induce hemoglobin synthesis in K562 cells. Different inducers induced different patterns of embryonic hemoglobin synthesis but never any adult hemoglobin synthesis. PMID- 6264440 TI - Colloidal gold--low density lipoprotein conjugates as membrane receptor probes. AB - We have developed a method for conjugating low density lipoproteins (LDL) with colloidal gold. Conjugation, complete after 1 min, occurs by electrostatic adsorption of the LDL to the negatively charged gold particle. Each conjugate consists of approximately eight biologically active LDL molecules clustered around a central 19-nm gold granule. Acidic (pH 4), alkaline (pH 9), or high ionic (600 milliosmolar NaCl) environments do not dissociate the conjugate. Colloidal gold is an electron-dense, nondegradable marker that is easily identified within the cell and serves as a valuable probe for studying receptor binding and endocytosis. By using a modified method of ruthenium red staining, the LDL molecules of the conjugate can be directly visualized when they are bound to the cell surface receptor. Receptor binding (4 degrees C) of the conjugate by cultured human fibroblasts reveals that the gold granule is positioned 18-21 nm from the coated pit region of the membrane. This distance, similar to the diameter of LDL, suggests concomitant internalization of the receptor during vesicular endocytosis and early lysosomal incorporation (10 min at 37 degrees C). Continued internalization (30-60 min at 37 degrees C) results in the formation of free pools of gold within the lysosome. PMID- 6264441 TI - Detection of a common feature in several human tumor cell lines--a 53,000-dalton protein. AB - Human cell lines, whether derived from spontaneous tumors or transformed in vitro with simian virus 40, were found to contain a 53,000-dalton phosphoprotein (pp53) in contrast to normal human cells in which this protein was not detected. Isoelectric focusing showed that pp53 comprised several species in both simian virus 40-transformed and tumor cells. Comparison of the pp53 species from the various cell lines by partial proteolysis showed that they were similar but not identical. Among the 13 tumor cell lines examined, only 1 line, HeLa, did not contain detectable pp53. All the other tumor cell lines contained pp53, and it is suggested that this protein may be associated with their transformed state. PMID- 6264442 TI - Rescue of noncultivatable human rotavirus by gene reassortment during mixed infection with ts mutants of a cultivatable bovine rotavirus. AB - Fastidious human rotaviruses that did not undergo productive infection in tissue culture were rescued by genetic reassortment during mixed infection with a temperature-sensitive (ts) mutant of a cultivatable bovine rotavirus. In this manner, the genes of the fastidious rotavirus that restricted growth in vitro were replaced by the corresponding genes from a tissue culture-adapted rotavirus. We recovered genetically reassorted viruses that grew to high titer and were neutralized specifically by hyperimmune guinea pig type 1 or type 2 human rotavirus antiserum. Preliminary RNA analysis of these clones disclosed that they were indeed viruses with reassorted genes. PMID- 6264443 TI - Genetics of cell surface receptors for bioactive polypeptides: variants of Swiss/3T3 fibroblasts resistant to a cytotoxic chimeric insulin. AB - Insulin crosslinked to the catalytic fragment A of diphtheria toxin has previously been shown to be cytotoxic to insulin-responsive mouse BALBc/3T3 cells but noncytotoxic to insulin-nonresponsive variant IN-2 cells [Miskimins, W. K. & Shimizu, N. (1979) Biochem. Biophys. Res. Commun. 91, 143-151]. We have now used this cytotoxic chimeric insulin to select resistant variants of Swiss/3T3 fibroblasts. Of eight resistant colonies isolated, two proved to be deficient in insulin receptor and exhibited altered morphologies and growth rates. These variants, however, retained the ability to bind and respond to epidermal growth factor. Thus, this selection technique is effective for the isolation of variants specifically related to cellular binding and processing of insulin. Such variants will be advantageous for the genetic and biochemical characterization of the mechanism of insulin's action. PMID- 6264444 TI - Excision of transposon Tn5 is dependent on the inverted repeats but not on the transposase function of Tn5. AB - The excision of Tn5 from sites of insertion in the Escherichia coli genome was studied by examining the reversion of lac::Tn5 insertion mutations to lac+. We find that: (i) the frequency of excision depends on the site of Tn5 insertion, (ii) excision occurs efficiently in recA- cells, (iii) excision does not require a Tn5-encoded transposition function, and (iv) efficient excision requires the inverted repeats of Tn5. We propose that excision of Tn5 is similar to the formation of spontaneous deletions and occurs by slippage during DNA synthesis. PMID- 6264445 TI - Linkage of the four gamma subclass heavy chain genes. AB - The genes for the heavy-chain constant regions of the four gamma subclass immunoglobulins were identified in a set of overlapping mouse DNA fragments representing about 100 kilobase pairs (kb) of the mouse genome that was cloned from bacteriophage lambda libraries of BALB/c mouse embryo DNA. R-loop mapping studies show that the genes are located 5'-C gamma 3-34 kb-C gamma 1-21 kb-C gamma 2b-15 kb-C gamma 2a-3' and lie in the same transcriptional orientation. Two DNA segments, one of 19 kb and another of 15 kb, that surround the C gamma 2b and C gamma 2a genes, respectively, show considerable homology and implicate a tandem duplication mechanism in the evolution of this gene cluster. PMID- 6264446 TI - Cmu gene rearrangement of mouse immunoglobulin genes in normal B cells occurs on both the expressed and nonexpressed chromosomes. AB - We have examined the organization of heavy-chain immunoglobulin genes on both the expressed and nonexpressed chromosomes of normal B lymphocytes from allotype heterozygous (BALB/c X C57BL/J)F1 mice. The C mu genes of BALB/c mice are on 12.4 kilobase EcoRI and 13.1-kilobase Kpn I restriction fragments, whereas those of C57BL/J mice are on 13.6-kilobase EcoRI and 14.3-kilobase Kpn I restriction fragments, allowing the examination of rearrangements on each chromosome independently. B lymphocytes from spleen and Peyer's patches expressing both IgD and IgM of the BALB/c allotype were isolated with a fluorescence-activated cell sorter. EcoRI and Kpn I restriction digests were hybridized with a C mu gene containing probe. The C mu gene is present on both chromosomes. DNA rearrangements occur on both the expressed and nonexpressed chromosome within the 3.6-kilobase Kpn I/EcoRI restriction fragment containing the joining (JH) gene locus. We conclude that allelic exclusion of heavy-chain immunoglobulin gene expression is not mediated by JH-region DNA rearrangement of the expressed chromosome only. In contrast, analysis of the C kappa gene region from the same sorted B-cell DNA reveals a substantial quantity of germ-line context DNA. We also demonstrate that the deletions observed on the Eco RI fragment containing the C mu gene in myeloma cells and in C mu gene-containing recombinant DNAs do not usually occur in normally differentiating B lymphocytes and are likely to be confined to myeloma tumor cells. PMID- 6264447 TI - Monoclonal antibodies against antigens displayed on a progressively growing mammary tumor. AB - We have produced lymphocyte hybridomas between mouse myeloma cells and either spleen cells of C3H/f/C57BL/6 mice bearing the Mm5mt/c1 tumor-producing murine mammary tumor virus (MMTV) or spleen cells from Fisher rats inoculated with the same tumor. Two classes of hybridoma-secreted monoclonal antibodies were obtained. In the first class are IVC11, IIIA1, and VE7, each of which precipitated a 52,000-dalton protein from 125I-labeled purified preparations of MMTV and [3H]glucosamine-labeled Mm5mt/c1 cell extracts. A second class of monoclonal antibodies, represented by IC12 and IIIB5, reacted specifically with C3H MMTV-secreting cells in radioimmunoassays (RIA) with whole cells and did not precipitate proteins with labeled virus or metabolically labeled Mm5mt/c cell extracts. IC12 and IIB5 could be distinguished from each other in a RIA in which antigen discs were prepared from a membrane preparation of Mm5mt/c1 cells. In this assay, IC12 antibody was blocked from reacting with discs precoated with goat anti-MMTV, and IIB5 antibody was not. PMID- 6264448 TI - A brain membrane protein similar to the rat src gene product. AB - We report the purification to homogeneity of a 20,000-dalton, transformation related, rat cell membrane protein. This protein, p20, was originally identified in preparations of a defective woolly monkey leukemia virus pseudotype of Kirsten sarcoma virus. The chromatographically purified p20 was an acidic hydrophobic protein, capable of specifically binding GTP (dissociation constant = 15 microM). This nucleotide binding property and other previously reported characteristics were similar to properties ascribed to the Harvey sarcoma virus src gene product. p20 also appeared similar to this src gene product when immunoprecipitates of both proteins were directly compared by one- and two-dimensional NaDodSO4 gel electrophoreses. However, the proteins were not identical, because their tryptic maps differed. Using a competition radioimmunoassay, we have measured the concentration of p20 in cells, viruses, and rat tissues: p20 was not encoded by rat sarcoma viruses because it was increased only slightly after Kirsten sarcoma virus transformation of rat cells and was not increased in nonrat cells transformed by the Kirsten or Harvey sarcoma virus. Remarkably, of 10 rat tissues examined, p20 was found predominantly in brain, specifically in the membranes. PMID- 6264449 TI - Herpes simplex virus thymidine kinase activity of thymidine kinase-deficient Escherichia coli K-12 mutant transformed by hybrid plasmids. AB - A hybrid plasmid (pAGO) that contains the herpes simplex virus type 1 (HSV-1) thymidine kinase (TK) gene in the form of a 2-kilobase-pair (kbp) Pvu II fragment inserted at the Pvu II site of plasmid pBR322 was used to transform TK- Escherichia coli K-12 strain KY895. pAGO-transformed KY895 cells exhibited partially restored ability to incorporate [3H]dThd into DNA and an HSv-1-specific TK activity. Bacteria cured of plasmid pAGO (or transformed by plasmid pBR322) did not show enhanced incorporation of [3H]dThd into DNA or HSV-1 TK activity. Plasmid pMH1A was derived from pAGO by deletion of 2067 bp of DNA sequence from pBR322 and 105 bp from the HSV-1 TK gene. E. coli K-12 strain KY895 cells transformed by pMH1A did not show enhanced incorporation of [3H]dThd into bacterial DNA, although pMH1A DNA isolated from transformed KY895 cells, like pAGO DNA, did transform TK- mouse fibroblast [LM(TK-)] cells to the TK+ phenotype. The expression of HSV-1 TK activity by E. coli K-12 suggests that intervening sequences may be absent from the coding region of HSV-1 tk or that the coding region of the gene possesses short intervening sequences which do not disrupt the translational reading frame. PMID- 6264451 TI - Characterization of angiotensin receptors on bovine adrenal fasciculata cells. AB - We have further characterized angiotensin receptors on bovine adrenal fasciculata cells whose presence was previously demonstrated by the intrinsic agonistic activity of angiotensin II (AII), dex-Asp1-AII, angiotensin I (AI), and des-ASp1 AI on steroidogenesis. The specific binding of AII and des-Asp1-AII labeled with 125I to dispersed bovine fasciculata cells was studied. For both peptides, a single class of binding sites accounted for the data with a mean (+/- SEM) Ka value of 0.23 +/- 0.123 X 10(8) liters/mol for AII and 0.68 X 10(8) liters/mol for des-Asp1-AII. The concentration at which unlabeled AII and des-Asp1-AII displaced 50% of the tracers (Kd) was similar to that at which they induced half maximal stimulation of steroidogenesis (Kact). For AI and des-Asp1-AI, Kd greater than Kact. Analogs of AII or des-Asp1-AII with antagonistic properties upon steroidogenesis competed also with binding of the tracers. Corticotropin (ACTH) did not inhibit binding. Although ACTH stimulated the formation of cyclic AMP, none of the angiotensins with intrinsic activity did so. Calcium, but not potassium, appeared to potentiate the steroidogenic activity of AII. These data suggest that there is a single class of receptors for angiotensins and analogs in zona fasciculata. These receptors show characteristics that differentiate them from ACTH receptors in zona fasciculata or angiotensin receptors in zona glomerulosa cells. PMID- 6264450 TI - Direct visualization of receptors for thyrotropin-releasing hormone with a fluorescein-labeled analog. AB - Thyrotropin-releasing hormone (TRH) binds to specific receptors on GH4C1 pituitary tumor cells. A fluorescently labeled analog of TRH was synthesized by coupling pGlu-His-ProNH(CH2)6NH2 to fluorescein isothiocyanate. The fluorescein labeled peptide (FL-TRH) stimulated prolactin synthesis and release by GH4C1 cultures and bound to TRH receptors with an apparent Kd of 400 nM. Binding of FL TRH to unfixed, viable GH4C1 cells was followed by fluorescence microscopy. After incubation with 1.4 microM FL-TRH for 1 hr at 37 degrees C, the surface of all cells was fluorescent and patches of intense fluorescence were evident. Control cultures incubated with FL-TRH and excess TRH were not fluorescent, and a line of pituitary tumor cells which lacks TRH receptors displayed little fluorescence after incubation with FL-TRH. When GH4C1 cells were incubated with FL-TRH for 1 hr at 37 degrees C and then with excess TRH for an additional 1 hr, the fluorescence associated with the cells was diminished to control levels. The results demonstrate that the fluorescein-labeled peptide labels specific TRH receptors. PMID- 6264452 TI - Interaction of human diferric transferrin with reticulocytes. AB - Methods have been devised for preparing human transferrin with a different isotope of iron selectively labeling each of the two iron binding sites and for determining the distribution of radioiron among transferrin molecules. When diferric human transferrin was exposed to human or animal reticulocytes, there was an equal contribution of radioiron from the acid-stable and acid-labile sites. In this delivery, both atoms of iron were removed simultaneously from the diferric transferrin molecule, converting it to apotransferrin. At similar iron concentrations the amount of iron delivered by diferric transferrin was twice that delivered by monoferric transferrin. PMID- 6264453 TI - Purification of the opiate receptor from rat brain. AB - The opiate receptor was purified from a Triton-solubilized preparation of rat neural membranes by the use of affinity chromatography. The affinity gel was prepared by coupling 14-beta-bromoacetamidomorphine, a newly synthesized ligand, to omega-aminohexyl-Sepharose. After elution of the nonspecific proteins with 50 mM Tris (pH 7.5), the receptor proteins were eluted with 1 microM levorphanol or etorphine. NaDodSO4/polyacrylamide gel electrophoresis revealed three major proteins associated with the opiate receptor, having molecular weights of 43,000, 35,000, and 23,000. The purified receptor binds 10(-11) mol of dihydromorphine/per mg of protein, with a Kd of 3.8 X 10(-9) M. Other opiates, naloxone, and methionine-enkephalin, inhibit [3H]dihydromorphine binding in a manner similar to that observed with intact and solubilized neural membranes. PMID- 6264454 TI - Localized binding of [3H]muscimol to synapses in chicken retina. AB - Binding sites for [3H]muscimol, an analogue of gamma-aminobutyric acid (GABA) were localized in the synaptic layers of chicken retina by light microscopic and electron microscopic autoradiography. Light microscopic autoradiography of cryostat sections incubated in [3H]muscimol or [3H]GABA revealed identical binding patterns: a band over the inner plexiform layer (IPL) and a band over the outer plexiform layer (OPL). This binding pattern differed from the uptake pattern for [3H]GABA: labeling over horizontal, amacrine, and ganglion cell bodies as well as very intense labeling over lamina 5 in the proximal IPL. Statistical analysis of electron microscopic autoradiography data from the IPL indicated that only amacrine synapses bind [3H]muscimol (i.e., make GABAergic synapses). Processes of amacrine, bipolar, or ganglion cells can be postsynaptic to these amacrine synapses. The highest concentration of synapses binding [3H]muscimol occurred in laminae 2 and 4 of the IPL and not in lamina 5 as might be expected from the density of [3H]GABA uptake. In the OPL, [3H]muscimol binding occurred over specialized junctions proximal to photoreceptor terminals. In cone receptor terminals, [3H]muscimol binding was suspected near horizontal cell dendrite/receptor terminal membranes lateral to the synaptic ribbon, supporting the hypothesis that horizontal cells are involved in a GABAergic feedback loop with cone terminals. We conclude that the synaptic binding pattern provides a more accurate concept of GABAergic synaptic interaction than does the uptake pattern for [3H]GABA because the two patterns in the IPL are not related. PMID- 6264455 TI - Radioimmunoreactivity and receptor-binding activity of the recombined molecule obtained by complementation of two fibrinolysin fragments of ovine prolactin. AB - The recombined molecule obtained by complementation of two fibrinolysin fragments of ovine prolactin (oPRL) has been characterized by radioimmunoassay and radioreceptor assay. The recombinant alone exhibits very low radioimmunoreactivity and radioreceptor activity. However, in the presence of excess fragment oPRL-(1-53), which does not compete with oPRL in either assay, the recombinant has 101% of the radioimmunoreactivity and only 13% of the radioreceptor activity. The result shows that the low activity of the recombinant when assayed alone is due to dissociation of the molecule. When the molecule is completely in the recombined form in the presence of excess oPRL-(1-53), it retains full immunoreactivity but only part of the radioreceptor activity. PMID- 6264456 TI - Fructose-bisphosphatase as a substrate of cyclic AMP-dependent protein kinase. AB - We have tested rat liver fructose-bisphosphatase (D-fructose-1,6-bisphosphate 1 phosphohydrolase, EC 3.1.3.11) and three other gluconeogenic fructose bisphosphatases as substrates for the catalytic subunit of cyclic AMP-dependent protein kinase. In contrast to the rat liver enzyme, homogeneous preparations of mouse liver, rabbit liver, and pig kidney fructose-bisphosphatase could not be phosphorylated by the kinase. Comparative sodium dodecyl sulfate/polyacrylamide gel electrophoresis of the four above fructose-bisphosphatases revealed that the subunit molecular weight of the isolated rat liver enzyme (ca. 40,000-42,000) was greater than that of mouse liver, rabbit liver, and pig kidney fructose bisphosphatases (ca. 36,000-37,000). Treatment of 32P-labeled rat liver fructose bisphosphatase with trypsin resulted in the conversion of the rat liver enzyme to an active species with a subunit molecular weight identical to that of the three other enzymes, with complete loss of the 32P-labeled site. Identical trypsin treatment of pig kidney fructose-bisphosphatase caused no change in the molecular weight of the enzyme. The results suggest that the purified mouse liver, rabbit liver, and pig kidney fructose-bisphosphatases are not substrates for the cyclic AMP-dependent protein kinase in vitro because they lack the phosphorylation-site peptide. PMID- 6264457 TI - DNA sequences similar to those around the simian virus 40 origin of replication are present in the monkey genome. AB - We report the molecular cloning of African green monkey genomic DNA segments that include regions of homology to the origin of replication of simian virus 40 (SV40). Three clearly different cloned segments 14 to 17 kilobase pairs (kb) long were isolated from a genomic library in lambda phage. We estimate that each of the three is repeated fewer than four times in the monkey genome. The SV40-like regions represent a small portion of the cloned segments, and these regions cross hybridize only weakly with one another. One of the three segments is described here in detail. Although the entire segment occurs only once or twice in the monkey genome, it contains DNA sequences (other than the SV40-like sequences) that are repeated elsewhere in the genome including in the other two cloned segments. The homology to SV40 is contained within about 300 base pairs of monkey DNA and is limited to the region around the viral replication origin. The nucleotide sequence of the SV40-like region was determined. It contains a large number of short stretches homologous to three specific noncoding domains around the SV40 origin of replication: the 27-base-pair region of dyad symmetry, the first set of (short) repeats that occur just on the late side of the origin, and, further in the late direction, the two 72-base-pair-long repeats. Although these components are grouped in the monkey DNA, as they are in SV40 DNA, their relative juxtaposition is scrambled. PMID- 6264458 TI - Hormone-responsive expression of an endogenous proviral gene of mouse mammary tumor virus after molecular cloning and gene transfer into cultured cells. AB - A recombinant lambda phage containing mouse mammary tumor virus (MMTV) proviral DNA was isolated from a gene library constructed from GR mouse liver DNA. Restriction enzyme analyses reveal that the cloned molecule contains a copy of one of the GR endogenous MMTV proviruses flanked on both sides by 2--3 kb of mouse genomic DNA. In this report we have examined the expression of the cloned MMTV provirus after cotransfection with the herpes thymidine kinase (TK; ATP:thymidine 5'-phosphotransferase,, EC 2.7.1.21) gene and integration into mouse LTK- cells. Nine individual TK+ transformants were selected, and all were found to contain MMTV-transfected DNA. One of the TK+ transformants was chosen for further study. Total poly(A)-containing RNA was isolated from the cells, and liquid hybridization analyses with MMTV cDNA showed that it contained 0.02% MMTV specific RNA. The sizes of the MMTV-specific species were determined and found to correspond to the 35S and 24S mRNAs synthesized in MMTV-infected cells. Glucocorticoid hormones have been shown to increase the concentration of MMTV RNA in virus-infected cultured cells. Therefore, we tested the effect of dexamethasone on the concentration of MMTV-specific RNA in cells transfected with the MMTV proviral DNA. The amount of MMTV-specific poly(A)-containing RNA found in the cells grown in the presence of hormone was 0.17%. Therefore, dexamethasone causes an 8-fold increase in the amount of MMTV-specific RNA in mouse cells containing several copies of a cloned and transfected MMTV proviral gene. PMID- 6264460 TI - Analysis of avian myeloblastosis viral RNA and in vitro synthesis of proviral DNA. AB - Two virus-specific RNA species of 7.5 and 7.0 kilobases have been identified in avian myeloblastosis virus (AMV) by denaturing gel electrophoresis and blot hybridization analysis, and they were found to be in a 10:1 ratio. The individual RNAs direccted the cell-free synthesis of the 76,000-dalton "gag" protein and the 180,000-dalton "gal-pol" protein, thereby demonstrating 5' sequence homology of approximately 4.9 kilobases between the two species. Synthesis of these two precursor proteins by the AMV genome indicates structural differences between AMV and other avian acute leukemia viruses. The two viral RNAs were transcribed into complete cDNA copies with AMV DNA polymerase. Linear proviruses were found to be 90--100% resistant to S1 nuclease. Analysis of single-stranded transcripts demonstrated two distinct species of 2.6 and 2.3 x 10(6) daltons, and analysis of duplexes formed from the single-stranded transcripts demonstrated species of 5.2 and 4.0 x 10(6) daltons. PMID- 6264459 TI - Identification and purification of the Lon+ (capR+) gene product, a DNA-binding protein. AB - The polypeptide product of the lon (capR) gene was identified and partially purified from bacterial strains homozygous for the capR(+) or capR9 (ochre mutation) alleles cloned with pSC101. A 94,000-dalton polypeptide was identified as the lon (capR) gene product. Studies of binding to DNA cellulose columns and nitrocellulose filters indicate that the capR(+) and capR9 proteins bind DNA. PMID- 6264462 TI - Covalent crosslinking of human chorionic gonadotropin to its receptor in rat testes. AB - The bifunctional crosslinking reagents disuccinimidyl suberate and dithiobis(succinimidyl propionate) were used to attach 125I-labeled human chorionic gonadotropin (125I-hCG) covalently to rat testicular membranes. The extent of crosslinking was dependent on time and concentration; routinely, 30% of the specifically bound hormone was covalently linked to the membranes in the presence of 0.5 mM crosslinking reagent when incubated at 25 degrees C for 15 min. Excess unlabeled hCG blocked the crosslinking of 125I-hCG to the membranes. When solubilized with Triton X-100 and analyzed by sucrose density gradient centrifugation, both the native and the crosslinked hormone-receptor complex sedimented with an apparent Mr of 220,000. Thus, the receptor itself would have Mr 180,000. When the crosslinked complex was analyzed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis, the predominant species had a Mr of 123,000 and appeared to represent the labeled alpha subunit of hCG covalently linked to a membrane component. The Mr of this receptor component would be 100,000, a value approximately half that of the Triton X-100-solubilized receptor. Thus, the membrane receptor for hCG may consist of a dimer of two binding subunits or a binding subunit associated with one or more additional subunits that might play a coupling or regulatory function. PMID- 6264461 TI - Abelson murine leukemia virus: molecular cloning of infectious integrated proviral DNA. AB - The integrated proviral genome of Abelson murine leukemia virus (A-MuLV) was cloned in lambda gtWES . lambda B bacteriophage after EcoRI endonuclease digestion and enrichment of proviral sequences by sequential RPC-5 column chromatography and agarose gel electrophoresis. Recombinant DNA clones containing a 7.8-kilobase-pair EcoRI insert were shown to have the entire integrated A-MuLV genome with both 5' and 3' ends flanked by mink cellular DNA sequences. This DNA fragment was shown to induce focus transformation upon transfection of NIH/3T3 mouse cells. Moreover, focus-forming virus could be rescued from transformed nonproducer cells upon superinfection with a type C helper virus. A polyprotein of molecular weight 120,000 (p120) containing murine leukemia virus gag gene determinants was invariably deteced by immunoprecipitation analysis of individual transformants induced by the 7.8-kilobase-pair DNA. Molecularly cloned integrated A-MuLV in its infectious form should be of use in elucidating the mechanisms involved in transformation by this virus. PMID- 6264464 TI - Overproduction of the free radical of ribonucleotide reductase in hydroxyurea resistant mouse fibroblast 3T6 cells. AB - Hydroxyurea inhibits the activity of ribonucleotide reductase (ribonucleoside diphosphate reductase; 2'-deoxy-ribonucleoside-diphosphate:oxidized-thioredoxin 2'-oxidoreductase, EC 1.17.4.1) in bacteria and mammalian cells. The reductase from Escherichia coli consists of two nonidentical subunits (B1 and B2) and hydroxyurea acts by specifically destroying a tyrosine free radical of B2 required for enzyme activity. The mammalian enzyme also consists of two nonidentical subunits (M1 and M2), only one of which (M1) has been obtained in pure form. By continuous culture at stepwise increasing drug concentrations, we have now obtained a 3T6 mouse fibroblast cell line with a 100-fold increased resistance to hydroxyurea. Extracts from resistant cells showed a 3- to 15-fold increase in reductase activity. The amount of M1 protein was not increased. The amount of M2 protein could not be measured directly, but the M2 activity in extracts from resistant cells (but not normal cells) showed an EPR spectrum very similar to that of the tyrosine radical of the bacterial B2 subunit. We propose that resistance to hydroxyurea is caused either by overproduction of the complete M2 subunit or by increased generation of the tyrosine radical within the M2 protein. It seems that either alternative mirrors a possible normal regulatory mechanism for the activity of the reductase. PMID- 6264465 TI - Identification and localization of a gene that specifies production of Escherichia coli DNA topoisomerase I. AB - A gene that specifies production of Escherichia coli DNA topoisomerase I (omega protein) was identified with the aid of a radioimmunoassay for this protein. E. coli DNA topoisomerase I was produced by Salmonella typhimurium merodiploids that harbored E. coli plasmid F' 123, but not by strains that lost this plasmid. Analysis of strains with spontaneous deletions of F' 123 showed that the gene, topA, required for production of the E. coli omega protein was between the trp operon and the cysB gene. Deletions that eliminated topA also eliminated the supX gene. We suggest that topA is the structural gene of E. coli DNA topoisomerase I and that topA is identical to supX. PMID- 6264463 TI - Vesicular stomatitis virus defective interfering particle containing a muted internal leader RNA gene. AB - The RNA of a unique long defective interfering particle (DI-LT2) derived from the heat-resistant strain of vesicular stomatitis virus (VSV) contains 70 nucleotides at its 3' end that are complementary to the 5' end of the VSV RNA. Following this region of terminal complementarity, there is a precise copy of the 3' end of the nondefective VSV RNA. The sequence homology between the DI-LT2 RNA and the 3' end of VSV RNA extends for at least 60 bases and probably for most of the length of the DI-LT2 RNA. The DI-LT2 particle is capable of transcription in vitro but produces only a short RNA [defective interfering (DI) particle product], which is encoded by the extreme 3' terminus of the DI RNA. Neither leader RNA nor capped VSV mRNAs are synthesized by DI-LT2, although competent templates for these are present. These data suggest that the 3'-terminal initiation is a prerequisite of the production of competent transcripts and that the sequence coding for leader RNA is not, by itself, sufficient for initiation. We propose a model for the origin of this DI particle, involving specific termination and resumption of replication, which is similar to that described previously for another class of DI particle RNAs. PMID- 6264466 TI - Specific in vitro initiation of transcription of simian virus 40 early and late genes occurs at the various cap nucleotides including cytidine. AB - High specific activity [beta-32P]ATP and [beta-32P]CTP were used to study in vitro transcriptional initiation and subsequent capping of simian virus 40 (SV40) early and later RNAs. More than 40% of the capped SV40 RNA synthesized in vitro was also polyadenylylated. With [beta-32P]ATP, only adenosine-containing caps were labeled and the incorporated radioactive phosphate was found exclusively in the beta position. Cap digestion patterns showed extensive qualitative and quantitative similarities between these 32P-labeled caps and caps labeled in vivo [Canaani, D., Kahana, C., Mukamel, A. & Groner, Y. (1979) Proc. Natl. Acad. Sci. USA 76, 3078--3082]. With [beta-32P]CTP, only early SV40 RNA was labeled, consistent with the absence of cytosine-containing caps in late transcripts. The [beta-32P]CTP-labeled cap was identified as m7GpppCmpU, which was previously identified as the major cap of in vivo labeled early SV40 mRNA [Kahana, C., Gidoni, D., Canaani, D. & Groner, Y. (1981) J. Virol. 37, 7--16]. This experiment provides biochemical evidence for eukaryotic RNA polymerase II initiation of transcription with CTP. The data imply that, on SV40 DNA, RNA polymerase II initiates transcription at multiple nucleotide sequences and capping occurs at the initiator nucleotide. PMID- 6264468 TI - A model for biological oscillations. AB - A model and computation for oscillatory phenomena observed in some biological processes that utilize ion gradients across a membrane is presented. The model contains two main features: (i) active H+ transport pathways in the membrane and (ii) key enzymes having a pH-dependent activity profile and either translocating H+ from outside or producing H+ as a product. With this model a very long period of oscillations, as observed in mitochondrial and circadian rhythms, could be quantitatively demonstrated. PMID- 6264467 TI - Fusion of Escherichia coli lacZ to the cytochrome c gene of Saccharomyces cerevisiae. AB - Hybrid genes between the Escherichia coli lacZ gene and the iso-1-cytochrome c (CYC1) gene of Saccharomyces cerevisiae were constructed by recombination in vitro. Each of the hybrid genes encodes a chimeric protein with a cytochrome c moiety at the amino terminus and an active beta-galactosidase (beta-D-galactoside galactohydrolase, EC 3.2.1.23) moiety at the carboxy terminus. When these hybrids are introduced into S. cerevisiae on plasmid vectors, they direct synthesis of beta-galactosidase. beta-Galactosidase levels directed by one such plasmid display the pattern of regulation normally seen for cytochrome c (i.e., a reduction of synthesis in cells grown in glucose). This plasmid contains one codon of CYC1 fused to lacZ, and the fused gene is preceded by the 1100 nucleotides that lie upstream from CYC1. An analysis of deletions in the upstream DNA suggests that sequences required for efficient transcription initiation of CYC1 lie within the DNA segment 250--700 base pairs upstream from the start of the CYC1 coding sequence. This region is at least 130 base pairs upstream from the "Hogness box" sequence that precedes the CYC1 coding sequence. PMID- 6264469 TI - beta-Endorphin: characteristics of binding sites in a neuroblastoma--glioma hybrid cell. AB - Specific binding of human beta-endorphin to NG108-15 cells is described; human beta-[Tyr27-3H2] endorphin was used as the ligand. The binding is time dependent and saturable; Kd = 0.3 nM and ka = 1.8 x 10(8) M-1 min-1. Under the conditions optimal for beta-endorphin binding, leucine-enkephalin has one-fourth to one third as many binding sites as beta-endorphin and its affinity is 7--10% that of beta-endorphin. Monovalent and divalent cations potently inhibit binding. Trypsin, phospholipase A, and N-ethylmaleimide reduce the ability of NG108-15 cells to bind beta-endorphin. beta-Endorphin analogs are able to fully inhibit the binding of beta-[Tyr27-3H2]endorphin, although enkephalins, morphine, and naloxone inhibit only 50--80%. PMID- 6264470 TI - A critique of the chemosmotic model of energy coupling. AB - The chemosmotic model provides a framework for visualizing energy-coupled reactions (vectorial reaction sequences, membrane-dependent gradient formation, and charge separation of reacting species) and a mechanism for energy coupling (indirect coupling between the driving and driven reaction sequences mediated by a membrane potential or a protonmotive force). The mechanistic parameters of this model have been examined from four standpoints: compatibility with the experimental realities, supporting evidence that is unambiguous, compatibility with the enzymic nature of energy coupling, and the capability for generating verifiable predictions. Recent developments that have clarified the mechanism of ion transport, the nature of the protonic changes that accompany energy coupling, and the enzymic nature of energy coupling systems have made such an examination both timely and necessary. After weighing the available evidence, it has been concluded that the chemosmotic principle of indirect coupling has no basis in fact and that it is physically unsound in respect to the mechanism of energy coupling and enzymic catalysis. PMID- 6264471 TI - Deletion mapping of sequences essential for in vivo transcription of the iso-1 cytochrome c gene. AB - The 5' termini of yeast CYC1 RNA molecules have been mapped, by nuclease S1 digestion of mRNA . DNA duplexes, to seven locations from 29 to 93 base pairs upstream from the initiating ATG codon. When the CYC1 gene is introduced into yeast in plasmid YEp13, substantially the same transcripts are made. Using this system to study in vivo gene expression, we measured the capacity of enzymatically produced DNA deletions to form the normal set of RNAs. Four regions of 5'-flanking DNA were identified as functional. Sequences within the region 242 to -139 are required for maximal CYC1 transcript formation; their deletion reduces transcription by a factor of 15 but does not change the pattern of 5' ends observed. Deletion of the sequence between -242 and -99 does not further change the overall transcript level but does affect the specificity of CYC1 mRNA starting. A deletion that extends from -242 to -75 causes both an additional shift in the pattern of 5' ends observed and a further large decrease (factor of 10--20) in CYC1 RNA level. Deletions that extend from -242 to -43, and particularly two deletions that extend still closer to the initiating ATG, cause the appearance of an abundant transcript which starts upstream of position -1078 and of minor transcripts starting in the region -325 to -245. PMID- 6264472 TI - Deficiency of low density lipoprotein receptors in liver and adrenal gland of the WHHL rabbit, an animal model of familial hypercholesterolemia. AB - The WHHL (Watanabe heritable hyperlipidemic) rabbit has been proposed as an animal model for human familial hypercholesterolemia. Homozygous WHHL rabbits have marked increases in the plasma level of low density lipoprotein (LDL), removal of LDL from their plasma is delayed, and LDL receptors are absent from their cultured fibroblasts [Tanzawa, K., Shimada, Y., Kuroda, M., Tsujita, Y., Arai, M. & Watanabe, Y. (1980) FEBS Lett. 118, 81--84]. We here report that membranes from the liver and adrenal gland of WHHL rabbits lack high-affinity LDL receptors. In normal rabbit membranes, binding of LDL to this receptor required calcium and is inhibited by EDTA. The LDL receptor binds rabbit 125I-labeled beta migrating very low density lipoprotein (beta-VLDL), which contains apoproteins B and E, as well as rabbit 125I-labeled LDL, which contains only apoprotein B. It does not bind high density lipoprotein or methyl-LDL. All of these properties are identical with those of the LDL receptor of cultured fibroblasts. We conclude that a deficiency of hepatic and adrenal LDL receptors contributes to the hypercholesterolemia of the WHHL rabbits. PMID- 6264474 TI - Polyamines are necessary for the survival of human small-cell lung carcinoma in culture. AB - Many human small-cell lung carcinoma culture lines grow as multicellular aggregate spheroids, for which high L-dopa decarboxylase activity is a marker. During the initial cell aggregation and the exponential growth phase, there is a marked increase in ornithine decarboxylase activity and an accumulation of polyamines. alpha-Difluoromethylornithine, a specific enzyme-activated, irreversible ornithine decarboxylase inhibitor, blocks the increase in ornithine decarboxylase activity and in polyamines and inhibits human small-cell lung carcinoma cell growth. After the onset of a decreased proliferation rate, the multicellular spheroid aggregates become poorly formed, cell loss ensues, and there is a decrease in L-dopa decarboxylase activity. These findings support the hypothesis that ornithine decarboxylase and the polyamines play an essential role not only in the proliferative phase but also in the viability of human small-cell lung carcinoma cells in culture. The results suggest that alpha difluoromethylornithine, a virtually nontoxic compound, may be potentially useful in the therapy of this human tumor. PMID- 6264475 TI - Constancy of somatic DNA organization in developmentally regulated regions of the Drosophila genome. AB - The purpose of this study was to test for the occurrence of changes in the organization, modification, or selective amplification of six developmentally regulated regions of genomic DNA during Drosophila development. Five of the regions contain structural genes, each of which maps at a single chromosomal site; the sixth region contains a dispersed segment that maps at about 30 different sites and appears to be transposable. The RNA transcripts and encoded proteins of the structural genes are major components of the fat body tissue in late third-instar larvae, in contrast to other larval tissues and young embryos in which the transcripts and proteins are hardly detectable. The dispersed segment shows the reverse developmental regulation: the amount of transcript is relatively high in young embryos and low in larval fat bodies. The test for changes in genomic DNA associated with the regulated expression of the six regions was based on comparative restriction mapping of the DNA from these sources. Genomic clones containing the transcribed and also flanking regions of DNA were used as probes to determine the positions of the complementary restriction fragments after electrophoresis in agarose gels. Each test, which involved digesting the genomic DNA samples with one of the endonucleases and probing with one of the clones, produced identical restriction maps for the different samples. The tests are capable of detecting changes in the organization of the cloned regions resulting from addition or removal either of endonuclease cleavage sites or of segments of DNA located between cleavage sites. Because the activities of several of the endonucleases, and probably all, are sensitive to methylation of one of the bases in the DNA recognition sequence, certain modifications of the cloned regions by methylation could also be detected. Although it is not certain that genomic reorganization or modification would have been detected by these tests, the number of endonucleases used was sufficient to provide persuasive evidence that such changes did not occur. Furthermore, the quantitative as well as qualitative similarities of the restriction maps in each test indicated that there was no significant selective amplification of the DNA within the cloned regions. PMID- 6264473 TI - Matrix protein in planar membranes: clusters of channels in a native environment and their functional reassembly. AB - Planar bilayers formed from Escherichia coli outer membrane vesicles exhibit conductance properties similar to those previously observed in bilayers reconstituted from aggregates of matrix protein, the major outer membrane protein. Discrete conductance steps are observed, reflecting voltage-dependent transmembrane channels. These exist in clusters which are activated by voltage. After activation, channels close with increasing potentials and reopen reversibly at lower voltage. Depending on the sign of the potential, two distinct closed states of the pores are observed. Cooperative interactions, hysteresis effects, relaxation times, and values of channel conductance depend on cluster size. These properties provide the reference data for the reconstitution of membrane function from individual components. Planar bilayers were formed from vesicles containing either solubilized matrix protein in a homogeneous trimeric state or bacterial glycolipid (lipopolysaccharide), or both. Activation of channel conductance required the presence of glycolipid and the formation of channel clusters, leading to conductance properties of the channels closely resembling those observed in native outer membranes. At very low concentrations of trimers, irreversible association to clusters by lateral diffusion was observed. Nearly quantitative recoveries of channels allowed the assignment of three pores per trimer. PMID- 6264476 TI - Evolutionary tree for apes and humans based on cleavage maps of mitochondrial DNA. AB - The high rate of evolution of mitochondrial DNA makes this molecule suitable for genealogical research on such closely related species as humans and apes. Because previous approaches failed to establish the branching order of the lineages leading to humans, gorillas, and chimpanzees, we compared human mitochondrial DNA to mitochondrial DNA from five species of ape (common chimpanzee, pygmy chimpanzee, gorilla, orangutan, and gibbon). About 50 restriction endonuclease cleavage sites were mapped in each mitochondrial DNA, and the six maps were aligned with respect to 11 invariant positions. Differences among the maps were evident at 121 positions. Both conserved and variable sites are widely dispersed in the mitochondrial genome. Besides site differences, ascribed to point mutations, there is evidence for one rearrangement: the gorilla map is shorter than the other owing to the deletion of 95 base pairs near the origin of replication. The parsimony method of deriving all six maps from a common ancestor produced a genealogical tree in which the common and pygmy chimpanzee maps are the most closely related pair; the closest relative of this pair is the gorilla map; most closely related to this trio is the human map. This tree is only slightly more parsimonious than some alternative trees. Although this study has given a magnified view of the genetic differences among humans and apes, the possibility of a three-way split among the lineages leading to humans, gorillas, and chimpanzees still deserves serious consideration. PMID- 6264477 TI - Base substitution in an intervening sequence of a beta+-thalassemic human globin gene. AB - beta globin gene fragments from a patient with homozygous beta+-thalassemia have been cloned and subjected to restriction endonuclease, nucleotide sequence, and in vitro trancription analyses. Restriction endonuclease mapping of the cloned gene fragments revealed no deletions or other rearrangements, and transcription of the thalassemic gene appeared to be normal in vitro. However, nucleotide sequence analysis of the beta+-thalassemic gene fragments permitted identification of a single base change in the body of the small intervening sequence. This nucleotide change creates a sequence much like that of the 3' splice site of the small intervening sequence. The presence of a potential anomalous splicing site as a result of this base change suggests a mechanism for defective posttranscriptional processing of beta globin mRNA precursor molecules in beta+-thalassemia. PMID- 6264478 TI - Stimulation of rheumatoid synovial cell collagenase and prostaglandin production by partially purified lymphocyte-activating factor (interleukin 1). AB - Human macrophages produce in culture a factor termed mononuclear cell factor (MCF) that increases the production of collagenase and prostaglandins by isolated adherent rheumatoid synovial cells. A factor with similar biologic activity is also produced by the murine macrophage cell line P388D1. By using a sequential purification scheme involving ammonium sulfate fractionation; chromatography on DEAE-cellulose, Sephacryl S-200, and phenyl-Sepharose; and discontinuous polyacrylamide gel electrophoresis, the P388D1 cell-derived, synovial cell stimulating factor was copurified with the lymphocyte-activating factor [LAF; interleukin 1 (IL 1)]. The specific activity of the partially purified LAF (IL 1) was approximately 15,000-fold higher than that of the LAF (IL 1) in the original P388D1 cell culture supernatant. On the basis of (i) the copurification of the P388D1 cell-derived LAF (IL 1) and synovial cell-stimulating factors; (ii) the similarity in cell of origin, molecular weight, and phenylglyoxal sensitivity of human MCF and murine LAF (IL 1); and (iii) the presence of LAF (IL 1) activity in preparations of partially purified human MCF, we have postulated that LAF (IL 1) may have effects on cell targets that are nonlymphoid in nature and also that human MCF may be similar to, or identical with human LAF (IL 1). The results of these studies have raised the possibility that LAF (IL 1) may play a role in macrophage-mediated activation of synovial cells and lymphocytes which are involved in the inflammatory responses associated with rheumatoid arthritis. PMID- 6264479 TI - Antibodies reactive with murine mammary tumor virus in sera of patients with breast cancer: geographic and family studies. AB - Sera of patients with breast cancer, of healthy women from the United States, East India, East Africa, and China, and of healthy women of American and Parsi families in which breast cancer occurred in several family members were assayed for levels of antibody reactive with the murine mammary tumor virus (MuMTV) by an enzyme-linked immunosorbent assay. Increased levels of antibody to MuMTV (absorbance greater than or equal to 0.4) were found in sera of 18.6% of American patients with breast cancer and of 2.8% of healthy American women and in 38% of patients from India and 61.9% from East Africa (healthy, 26.9%). In contrast, antibody reactive with MuMTV was found in less than 5 of women with breast cancer from mainland China (healthy Chinese, 5.0%). Differences in serum MuMTV antibody levels between breast cancer patients in the four groups were found to be significant (P less than 0.0001). Studies of two families from the United States and of one Parsi family from India with genetic propensity to breast cancer showed that high levels of antibody to MuMTV were found in 33%, 71%, and 23% of healthy family members, respectively. The antibody to MuMTV was readily absorbed with purified MuMTV and gp52. In contrast, fetal calf serum, murine type c retroviruses, or erythrocytes from various species failed to absorb the antibody. PMID- 6264480 TI - Nuclear uptake of 1,25-dihydroxy[3H]cholecalciferol in dispersed fibroblasts cultured from normal human skin. AB - Because of the relative inaccessibility of known calciferol target tissues (i.e., intestine and bone), we examined fibroblasts derived from normal human skin and grown in tissue culture as a means of evaluating the interaction of 1,25 dihydroxycholecalciferol [1,25(OH)2D3] and its effector system. When dispersed, intact cells were used, nuclear uptake of 1,25-dihydroxy[23,24(n)3 H]cholecalciferol [1,25(OH)2[3H]D3) was temperature-dependent, optimal at 45 min at 37 degrees C, and saturable. In competition experiments with other calciferols, the 1,25(OH)2[3H]D3 uptake showed specificity indistinguishable from that reported for 1,25(OH)2D3 receptors from calciferol target tissues. Analysis of 1,25(OH)2[3H]D3 nuclear uptake in fibroblast strains from six normal adults (four male, two female) yielded an average binding capacity (R0) of 10,600 +/- 2,000 (SEM) nuclear sites per cell and an apparent dissociation contant (Kd) of 0.50 +/- 0.07 (SEM) x 10(-9) M. Donor sex, donor age, or anatomic site of origin of the cell line did not affect the characteristics of uptake. Similar nuclear uptake was demonstrable with cultured MCF-7 cells (derived from human breast cancer) when assayed in the same fashion. When hypertonic extracts of nuclei obtained from skin fibroblasts incubated with 1,25(OH)2[3H]D3 were subjected to centrifugation on sucrose gradients, a single peak of radioactivity sedimented at approximately 3 S; when excess 1,25(OH)2D3 was coincubated during the cellular uptake phase, this 3S peak was not observed. Molybdate was an essential buffer component for receptor stabilization during cell fractionation and sedimentation analysis. In summary, by using fibroblasts cultured from normal human skin, we have identified a process of nuclear uptake of 1,25(OH)2[3H]D3 with the affinity, saturability, and specificity characteristics of a steroid hormone--receptor interaction. This method should be useful in studying 1,25(OH)2D3 recept physiology in cells from normal persons as well as in cells from patients who have disorders in the responsiveness of calciferol target tissues. PMID- 6264481 TI - Membranes and phospholipids of liver mitochondria from chronic alcoholic rats are resistant to membrane disordering by alcohol. AB - Using the spin probe 5-doxylstearic acid, we studied the structural perturbations of rat liver mitochondrial membranes produced by exposure to ethanol in vitro and by chronic ethanol feeding. The addition of ethanol in vitro to mitochondria from control animals appears to "fluidize" the membranes, as evidenced by a pronounced decrease in the order parameter. By contrast, in membranes from rats fed ethanol chronically, there was no effect on the order parameter. This resistance of the mitochondrial membranes from chronically intoxicated animals to the fluidizing effect of ethanol probably results from a change in the composition of the phospholipids, because the same differential response to ethanol was observed upon using vesicles of mitochondrial phospholipids extracted from control and chronically treated rats. In the presence of 0.025--0.1 M ethanol, a range that prevails in the blood of chronic alcoholics, the order parameter of mitochondrial membranes from rats fed ethanol was comparable to that of control membranes without ethanol in vitro. Analysis of extracted mitochondrial phospholipids showed that the cardiolipin from ethanol-fed animals had fatty acyl residues that are more saturated than those of controls. These findings point to the underlying molecular mechanism of our previous observation that mitochondria from chronic alcoholic rats are more resistant to uncoupling by ethanol at physiological temperature [Rottenberg, H., Robertson, D. E. & Rubin, E. (1980) Lab. Invest. 42, 318--326]. We suggest that an adaptive change in the phospholipid composition leads to structural alterations, which result in increased resistance to disruption of mitochondrial membranes by ethanol. These changes in lipid composition and structure may explain many, if not all, of the mitochondrial abnormalities that have been previously reported to result from chronic ethanol intoxication. PMID- 6264482 TI - Defects of receptor-mediated low density lipoprotein catabolism in homozygous familial hypercholesterolemia and hypothyroidism in vivo. AB - The role of low density lipoprotein (LDL) receptors in the pathogenesis of hereditary and acquired forms of hypercholesterolemia has been investigated in vivo by simultaneously determining total and receptor-independent LDL catabolism with 125I-labeled LDL and 131I-labeled LDL coupled with cyclohexanedione. Receptor-mediated catabolism of LDL, determined as the difference between the turnover of 125I and 131I, was found to be virtually absent in two homozygotes with familial hypercholesterolemia and markedly reduced in a hypothyroid patient. Treatment of the latter with L-thyroxine markedly stimulated receptor-mediated catabolism and reduced LDL levels as did cholestyramine administration in a control subject. Reduction of LDL levels by plasma exchange in a control subject and homozygote had no such effect. These results demonstrate the existence of an intrinsic and almost total defect of receptor-mediated LDL catabolism in homozygous familial hypercholesterolemia and demontrate an analogous but reversible abnormality in hypothyroidism. PMID- 6264483 TI - Rous sarcoma virus infection of synchronized cells establishes provirus integration during S-phase DNA synthesis prior to cellular division. AB - Synchronized chicken embryo fibroblasts, prepared by addition of serum to stationary cells arrested in Go, were exposed to the Prague strain of Rous sarcoma virus. At different times during the cell cycle, high molecular weight DNA was prepared from infected cells and examined for the presence of newly integrated viral DNA sequences. The results demonstrate that newly integrated viral sequences were first detected during S-phase DNA synthesis 9 hr after infection. The presence of colchicine prevented cellular division and delayed the appearance of progeny virus but it did not affect the appearance of viral specific DNA in the high molecular weight fraction of cellular DNA. Our results indicate that provirus integration, occurring during S-phase DNA synthesis, does not require cell division. Previous experiments have demonstrated that Rous sarcoma virus infection of chicken embryo fibroblasts requires cell division to initiate viral RNA synthesis and the production of progeny virus. The findings presented in this report support the hypothesis that division of the infected cells is required for an event that controls viral expression at the level of the integrated provirus. PMID- 6264484 TI - Expression of the hepatitis B virus surface antigen gene in cell culture by using a simian virus 40 vector. AB - We have constructed a simian virus 40 recombinant carrying a fragment of DNA from hepatitis B virus. Cultured monkey kidney cells infected with this recombinant produce hepatitis B surface antigen. The antigen is excreted into the culture medium as 22-nm particles with the same physical properties, antigenic composition, and constituent polypeptides as those found in the sera of patients with type B hepatitis. PMID- 6264486 TI - Herpes simplex virus (type 1) thymidine kinase gene does not transform cells morphologically. AB - BALB/c-derived 10E2 cells were made thymidine kinase(TK)-negative and one isolated clone (B2) was used for studying morphological and biochemical transformations by herpes simplex virus (HSV) type 1 (strain 10412). The B2 cells displayed a "normal" flat appearance and were nontumorigenic in nude mice when tested at frequent intervals over a period of 45 subcultures. B2 cells infected with UV-irradiated HSV (UV-HSV) and maintained in normal growth medium showed foci of spindle-shaped cells after one subculture. The cells from these morphologically transformed foci were tumorigenic in nude mice and were TK negative. B2 cells infected with UV-HSV or transfected with the HSV-1 TK gene and maintained in TK-selective medium showed discrete colonies of cells which displayed a normal flat appearance and expressed the viral TK enzyme. These biochemically transformed B2 cells were nontumorigenic in nude mice. The findings with B2 cells indicate that biochemical and morphological transformations by HSV 1 are independent events and suggest that the HSV-1 TK gene is a suitable vehicle for introducing non-TK genes into cells to assess their transforming potential. PMID- 6264485 TI - A third class of avian sarcoma viruses, defined by related transformation specific proteins of Yamaguchi 73 and Esh sarcoma viruses. AB - The gag-linked transformation-specific protein (polyprotein) p80 of Esh avian sarcoma virus (ESV) has been compared by tryptic peptide mapping with the homologous protein p90 of Yamaguchi 73 avian sarcoma virus (Y73). p80 of ESV and p90 of Y73 were found to share all four of their major nonstructural, transformation-specific, methionine-containing peptides and to have at least seven cysteine-containing transformation-specific peptides in common. Two nonstructural cysteine-containing peptides unique for ESV p80 and three specific for Y73 p90 were also identified. None of these peptides were found in the transforming gene product pp60src of Rous sarcoma virus (RSV) or in the transformation-specific polyproteins p105 of avian sarcoma virus PRCII (PRCII) or p140 of Fujinami sarcoma virus (FSV). ESV p80 and Y73 p90 are phosphorylated, and their tryptic phosphopeptides appear to be identical. In each polyprotein two major phosphopeptides were demonstrated, one containing phosphoserine, the other phosphotyrosine. The latter serves as phosphoacceptor for the protein kinase activities (ATP:protein phosphotransferase, EC 2.7.1.37) associated with p80 and p90. These protein kinase activities were found to be functionally indistinguishable but could be easily distinguished from the activities associated with PRCII p105 and FSV p140 on the basis of their cation requirement and target site specificity. On that basis also, p80/p90-associated protein kinases were found to be more similar to the enzymatic activity of pp60src than to those associated with the PRCII and FSV transformation-specific polyproteins. These results document a close genetic relationship between the two independently isolated sarcoma viruses Y73 and ESV. On the basis of the relatedness of transformation-specific proteins, ESV and Y73 constitute class III of avian sarcoma viruses, with class I containing the various strains of RSV and class II encompassing FSV and PRCII. PMID- 6264488 TI - High-carbohydrate, high-fibre diets for diabetics. PMID- 6264489 TI - Slow release carbohydrate and the treatment of diabetes. PMID- 6264487 TI - Vitamin D: metamorphosis from nutrient to hormonal system. PMID- 6264490 TI - Murine leukemia viruses as chromosomal genes of the mouse. PMID- 6264491 TI - Abelson murine leukemia virus-induced transformation of immature lymphoid cells. PMID- 6264494 TI - Endocrine effects of ethanol infusion in normal subjects: modification by naloxone. PMID- 6264493 TI - Genetic influences on teratocarcinogenesis and parthenogenesis. PMID- 6264492 TI - The organization and evolution of cloned globin genes. AB - The globin genes represent a complex set of sequences that are expressed in a coordinate fashion during the development of red blood cells. while this complex family of genes may consist of as many as ten to fourteen members [34], three of these genes have now been cloned and their entire nucleotide sequence determined. As was initially observed in the case of beta globin major gene, all are encoded in three distinct coding blocks separated by two intervening sequences of DNA. Their intervening sequences of DNA are preserved, with respect to location, but are widely divergent, with respect to size and sequence. The divided information in each gene is edited and spliced together at the level of its initial RNA transcript which is complementary to the entire gene sequence including its intervening sequences. Structural correlation analyses have allowed us to identify sites in all three genes that might be responsible for the initiation of transcription, RNA splicing, and poly A addition. The function of these sites has been tested by cloning these genes in an animal virus vector SV40. Such animal virus hybrids have been used to infect tissue culture cells and have directed the synthesis of both alpha and beta mouse globin in cells of monkey origin. These studies indicate that such signals operate across species barriers and further indicate that the animal virus vector system will be useful in elucidating their function. PMID- 6264495 TI - Ethanol and neuronal metabolism. AB - The effect of ethanol on membrane enzymes (Na+, K+ and Mg2+ ATPases, 5' nucleotidase, adenylate cyclase) alcohol dehydrogenase, aldehyde dehydrogenase and superoxide dismutase were studied in nerve cells (established cell lines, primary cultures of chick and rat brain) cultured in the presence of 100 mM ethanol, and in total rat brain, following various ethanol treatments of the rats (20% ethanol as the sole liquid source, intraperitoneal injection). The results show a difference between neuronal and glial cells. Most of the observed changes in enzymatic activities returned rapidly to control values when ethanol was withdrawn from the culture medium or from the diet. Alcohol dehydrogenase was more stimulated by ethanol than aldehyde dehydrogenase; therefore acetaldehyde may be accumulated. The inhibition of superoxide dismutase activity may allow an accumulation of cytotoxic O2- radicals in nervous tissue and may explain the polymorphism of lesions brought about by alcohol intoxication. PMID- 6264496 TI - Acute and chronic catecholamine-ethanol interactions on rat brain (Na+ + K+) ATPase. AB - Noradrenaline (N) sensitizes rat brain (Na+ + K+)-ATPase to inhibition by low concentrations of ethanol (E). Only 1-N and not d-N was effective. The sensitization is also produced by other alpha-adrenergic agonists (adrenaline, phenylephrine), but not by isoproterenol, and is prevented by phentolamine but not by propranolol. The sensitization is greater with partially purified enzyme than with crude homogenates. N + E, like much higher concentrations of E alone, produced competitive inhibition with respect to K+ but uncompetitive or mixed inhibition with respect to Na+, Mg++ and ATP, and a reduced "physiological efficiency" of ATP utilization. All these changes were abolished by increasing K+ to 20 mM. After 3-week E treatment, with or without withdrawal, the N + E interaction was markedly reduced, though basal ATPase activity was increased only after withdrawal. Temperature-dependence studies (Arrhenius plots) indicated that sensitization occurs by alteration of activation energy only above the transition temperature. These findings suggest that alpha-agonists fluidize membrane lipids and thus facilitate conformational change of the enzyme by E, resulting in inhibition. PMID- 6264498 TI - Aversive factors in alcohol drinking in humans and animals. AB - In human subjects there is a wide range of response to the taste of alcohol in varying concentrations. What some people find totally aversive may be accepted with relish by others. Both individual and racial responses to ingested or injected alcohol can be aversive, since markedly dysphoric experiences can occur. Human studies also suggest that the euphorigenic properties of alcohol are very variable between subjects and that this correlates with characteristics of biogenic amines present in the body. Except for relatively low concentrations, the laboratory rat, used commonly in alcohol drinking experiments, avoids the selection of alcohol. Paralleling human studies are animal investigations that manipulate the levels of chemical substances in the brain and demonstrate effects of this upon alcohol self-selection. When certain tetrahydroisoquinolines or beta carboline substances are infused into the brain of the rat or monkey, the aversive nature of orally ingested alcohol, particularly in very high concentrations, is overcome. In contrast, however, when a high dose of a tetrahydropapaveroline is infused, the animal's volitional intake of alcohol is inhibited and even weak concentrations of alcohol are rejected. The possible mechanisms for this phenomenon and the recent investigations of agents acting on CNS opiate receptors in reinstating alcohol aversion are considered. PMID- 6264497 TI - Ethanol effects on synaptic glutamate receptors and on liposomal membrane structure. AB - Exposure of synaptic plasma membranes to 50 mM ethanol in vitro brought about a 3.5 degrees C decrease in the transition temperature of the high affinity glutamate binding process in these membranes. Ethanol had no effect on the energy of activation of glutamate binding below the transition temperature but decreased the energy of activation above the transition temperature. Electron paramagnetic resonance (EPR) studies of lipid organization of egg lecithin and bovine brain phospholipid liposomes indicated that ethanol at low concentrations (0.04--2 mM) caused small increases in the rigidity of the membrane near the surface. At higher concentrations (0.04--2 M) ethanol brought about increasing fluidization of both the surface and inner areas of the bilayer. Even at 4 mM concentration ethanol enhanced the ordered to fluid state transition of liposome membranes as shown by a 5.2 degrees C and 1.9 degrees C decrease in the transition temperatures of the membrane determined with the cholestane EPR probe. PMID- 6264499 TI - Nicotinamide, inosine and hypoxanthine, putative endogenous ligands of the benzodiazepine receptor, opposite to diazepam are much more effective against kynurenine-induced seizures than against pentylenetetrazol-induced seizures. AB - Nicotinamide (NAM, 1000 mg/kg), inosine (INS, 1000 mg/kg), hypoxanthine (HXT, 500 mg/kg), putative endogenous ligands of the benzodiazepine receptor, and nicotinic acid (NA, 500 mg/kg) diminished DL-kynurenine-(DL-K, 50 micrograms ICV) induced seizures in C57BL/6 adult male mice and only prolonged the latency of pentylenetetrazol (PTZ, 500 micrograms iCV) seizures. The same effect was previously observed when PTZ was administered IP. In albino male BALB/c and SHR (bred from Swiss) mice only NA was effective against DL-K. Diazepam in a dose of 0.5 mg/kg prevented PTZ-induced seizures in half of the animals but even in dose of 10 and 20 mg/kg it was ineffective against DL-K. When injected ICV NAM (1 and 10 micrograms), INS (10 micrograms) and HXT (10 micrograms) prevented seizures induced by DL-K and were ineffective against seizures induced by PTZ. It is suggested that if NAM, INS and HXT are of functional importance in the central nervous system, they can act as antagonists of endogenous brain kynurenine. NA and NAM are suggested to be functional feedback inhibitory regulators of the kynurenine pathway of metabolism of tryptophan. PMID- 6264500 TI - Behavioral effects of temperature sensitive mutations affecting metabolism of cAMP in Drosophila melanogaster. AB - Temperature-sensitive mutations affecting metabolism of cAMP were obtained in Drosophila melanogaster to elucidate the possible involvement of cAMP in behavior. Temperature-dependent hypersensitivity to theophylline, propranolol and dihydroergotoxin following treatment with ethylmethanesulfonate was used to screen for such mutations in the X-chromosome. Biochemical analysis of cAMP content and activity of phosphodiesterase revealed two mutants with increased content of cAMP, 2 mutants with low activity of phosphodiesterase and 1 mutant with high activity of the enzyme. Locomotor activity of the ts-mutants correlated with cAMP content, increasing at 29 degrees C in mutants with an enlarged amount of cAMP and in mutants with low activity of phosphodiesterase and decreasing in the mutants with high activity of the enzyme. The latter mutant also failed to learn to avoid shock-associated odorant. One of the mutants with increased content of cAMP, but insensitive to propranolol, displayed better learning ability than the wild type. The learning performance of the mutants is interpreted proceeding from the metabolism of cyclic nucleotides in cholinergic and dopaminergic structures of the brain. PMID- 6264501 TI - On the neuropharmacology of harmane and other beta-carbolines. PMID- 6264502 TI - Reversal of guanethidine- and diethyldithiocarbamate-induced amnesia by peripherally-administered catecholamines. AB - The effect of peripherally-administered catecholamines on guanethidine- and diethyldithiocarbamate-induced amnesia of a PA training in mice was investigated. The amnesic effect of guanethidine could be blocked with 50 mg/kg DA, or 0.75 mg/kg NE when given either before, immediately, or 10 min after but not 90 min following PA. Epinephrine or a lower dose of DA could be attenuate the guanethidine-induced amnesia. The amnesic effect of diethyldithiocarbamate could be blocked with 50 mg/kg DA, 0.75 mg/kg NE or 0.5 mg/kg E when given either before, immediately or 10 ming after but not 90 min following PA. The amnesic effects of these compounds were interpreted in terms of their peripheral antiadrenergic actions. PMID- 6264503 TI - Mechanism of stress-induced subsensitivity to norepinephrine. AB - Chronic footshock stress in rats produces a persistent reaction in the sensitivity of the norepinephrine (NE)-cAMP generating system in the cerebral cortex, an effect similar to that reported after chronic antidepressant treatment. The present studies show that footshock-induced subsensitivity is not related to changes in either beta or alpha-1 adrenergic receptors, phosphodiesterase or total adenylate cyclase activity. The stress does not induce a small, selective decrease in binding at high affinity alpha-2 receptor sites but this change does not appear to explain the decreased responsiveness to NE. These data and related findings by others using restraint stress indicate that the mechanism of subsensitivity after chronic stress resembles in part that seen after antidepressants but may also involve additional phenomena which may not occur after the latter agents. PMID- 6264504 TI - Delta-9-Tetrahydrocannabinol stimulates receptive and proceptive sexual behaviors in female hamsters. AB - This experiment studied the effects of delta-9-tetrahydrocannabinol (THC) on lordosis responses and ultrasonic communication (measures of sexual receptivity and proceptivity, respectively) in female hamsters. Specifically, lordosis durations and rates of ultrasound production by estradiol-primed ovariectomized hamsters were observed following acute treatment with 1.5 mg/kg of THC, 500 micrograms of progesterone, or the injection vehicle. The results showed that THC can facilitate both lordosis and ultrasound production. Together with results from other laboratories, these data indicate that THC can stimulate female sexual behavior and suggest that this effect reflects a direct, nonhormonal, effect of THC on brain mechanisms for behavior. PMID- 6264505 TI - Cyclic nucleotides and aggressive behavior. AB - Cyclic nucleotides, particularly cyclic AMP, have been implicated as second messengers in neuronal activity. Attempts to demonstrate an association between endogenous cAMP or cGMP levels and rodent aggressive behavior have been only partially successful. Low levels of cAMP in rodent brain appear associated with lower levels of affective aggression. Consistent with this possible relationship is our finding that the infusion of dibutyryl cAMP into rodent cerebroventricles decreases aggressive behavior. The infusion of dibutyryl cyclic GMP, conversely, facilitates shock-induced fighting in the rat. PMID- 6264506 TI - A three-year clinical caries evaluation of the effect of a sodium fluoride-silica abrasive dentifrice. AB - This study was conducted to determine if the anticaries effectiveness of a 0.243% sodium fluoride-silica abrasive dentifrice is superior to a 0.4% stannous fluoride-calcium pyrophosphate dentifrice. A nonfluoride, calcium pyrophosphate abrasive placebo dentifrice was also included at one-third the sample size of the active treatment groups to estimate the level of efficacy of the sodium fluoride dentifrice. A total of 3,093 schoolchildren were randomly assigned at a ratio of 3:3:1 to the sodium fluoride dentifrice, the stannous fluoride dentifrice, or the placebo dentifrice, respectively. Caries examinations were made by the same examiner initially and after one, two, and three years of ad libitum product usage. After three years, the results showed that the group using the sodium fluoride dentifrice had significantly fewer DMF teeth and DMF surfaces increments than the group using the stannous fluoride dentifrice. The percent reductions for DMF teeth and DMF surfaces were 24.2% and 22.6%, respectively. Both groups using fluoride dentifrices also had significantly fewer DMF teeth and DMF surfaces increments than the group using the placebo dentifrice. PMID- 6264508 TI - Noradrenergic transmission in depression: under- or overfunction? AB - The pros and cons of the noradrenaline hypothesis of depression are examined and a critical assessment is made of the recent theory that antidepressants act by reducing the sensitivity of postsynaptic beta-adrenergic receptors, implying that depressed patients suffer from a overfunction and not underfunction of cerebral noradrenergic systems. The evidence that the latter are in some way involved in depression, although very probably other transmitter systems are also involved in this disease, is considered quite convincing. On the other hand, the subsensitivity of postsynaptic receptors occurring after antidepressive treatment is seen as a counterregulatory mechanism responding to an increased noradrenaline concentration in the synaptic cleft rather than as the cause of the antidepressant effect. It is stressed that it is the intensity of noradrenergic synaptic transmission that matters, i.e. the functional activity of integral system and not that of the pre-or postsynaptic parts alone. A model of the sequential occurrence of events influencing noradrenergic transmission during treatment with an uptake inhibitor is suggested which could explain both the latency of onset of the therapeutic response and the fact that some patients do not respond to the treatment. PMID- 6264507 TI - A three-year study of the effect of a sodium fluoride-silica abrasive dentifrice on dental caries. AB - The purpose of this study was to determine if a 0.243% sodium fluoride-silica abrasive dentifrice provides greater anticaries efficacy than a 0.4% stannous fluoride-calcium pyrophosphate abrasive dentifrice. A sample of 1,824 schoolchildren was randomly assigned to either the sodium fluoride dentifrice or the stannous fluoride dentifrice and examined clinically and radiographically for dental caries initially and after one, two, and three years of dentifrice usage. Two examiners independently examined each of the subjects for dental caries. After three years of ad libitum dentifrice usage, the results for both examiners showed that the group brushing with the sodium fluoride dentifrice had significantly lower DMF tooth and DMF surface increments than the group brushing with the stannous fluoride dentifrice. The percent reductions for DMF teeth were 14.8% and 10.5%, and for DMF surfaces 16.4% and 13.1% for the two examiners, respectively. PMID- 6264509 TI - Microdosimetric investigations on collimated fast-neutron beams for radiation therapy: I. Measurements of microdosimetric spectra and particle dose fractions in a water phantom for fast neutrons from 14 MeV deuterons on beryllium. AB - Lineal energy spectra of fast neutrons, produced by bombarding a thick beryllium target with 14 MeV deuterons, were measured with a proportional counter simulating a sensitive diamter of 2 micrometers. The mean neutron energy of the collimated beam was 6 MeV. The total lineal energy spectra, measured at different positions within a water phantom were separated into three different components: the gamma component, the recoil-proton component, and the component of heavier recoil ions. It is shown mathematically that the components of a linear energy spectrum thus derived allow the calculation of their fractional dose contributions. These dose fractions i.e. the gamma dose, the recoil-proton dose, and the dose fraction of heavier recoil ions, are shown as a function of the spatial position in the phantom. PMID- 6264510 TI - Microdosimetric investigations on collimated fast neutron beams for radiation therapy: II. The problem of radiation quality and RBE. AB - The correlation between radiation quality and cellular RBE of a mixed n-gamma field produced by a collimated fast-neutron beam produced by the bombardment of 14 MeV deuterons on Be in a water phantom is investigated. The microdosimetric parameters yF and YD are used for a physical description of the local distribution of radiation components. On the basis of the dose fractions of these components, the dependence of RBE on depth is calculated and is compared with experimental RBE data. Outside the beam centre, it is shown that the microdosimetric parameter y can be used for estimates of local changes of RBE, if particular conditions for the absorbed dose and for the range of neutron energies are met. The spatial distributions of y for the mixed radiation changes in RBE for equal absorbed doses of 1 Gy are at maximum 10% and thus perhaps negligible. PMID- 6264511 TI - Small-angle multiple scattering and spatial resolution in charged particle tomography. AB - The formulae for the RMS scattering angle given by small-angle multiple scattering theory are discussed and a correction to the standard Rossi formula is derived. Values of the correction factor are calculated for protons, alpha particles and heavy ions; these results show that the correction is important for protons and alpha-particles but negligible for heavy ions with mass number 12-40. The values of the RMS scattering angle and the RMS lateral displacement are calculated for a proton beam passing through water. For protons the correction for energy loss in thick targets is even more important. PMID- 6264512 TI - Reevaluating the theoretical model underlying the neurodevelopmental theory. A literature review. AB - The purpose of this paper is to evaluate the foundations of prevalent physical therapy technique based on the current research on motor control. The conceptual framework of the neurodevelopmental theory, as described in the writings of the Bobaths, is presented. Their explanations of central nervous system disorders and recommendations for intervention are based upon a unidirectional model of the nervous system in which postural and voluntary motion become two separate and distinct entities. Systems theory is an alternative model of nervous system structure. In systems theory, the organism is a circular network of interacting yet autonomous subsystems, rather than a vertical structure of descending controls. Relevant research that supports the systems viewpoint is discussed and applied to the theories in the neurodevelopmental approach. Thus, another model is offered for understanding the functioning of the central nervous system when it is intact and when it is in a pathological state. PMID- 6264513 TI - UV-enhanced reactivation in mammalian cells: increase by caffeine. PMID- 6264514 TI - Photoreactivation of ultraviolet irradiated non-dividing populations of ICR 2A frog cells. PMID- 6264516 TI - Operant feeding and drinking in pigs following intracerebroventricular injection of synthetic cholecystokinin octapeptide. PMID- 6264515 TI - Na+-K+ dependent ATP-ase modifications of skeletal muscle and myocardium of hypokinetic rats. PMID- 6264518 TI - Conjugative transfer of multiple-antibiotic resistance markers in beta-hemolytic group A, B, F, and G streptococci in the absence of extrachromosomal deoxyribonucleic acid. PMID- 6264517 TI - Obese mice and the satiety effects of cholecystokinin, bombesin and pancreatic polypeptide. PMID- 6264519 TI - Group Y incompatibility and copy control of P1 prophage. PMID- 6264520 TI - RecE independent deletions of recombinant plasmids in Bacillus subtilis. PMID- 6264521 TI - Fingerprinting and sequence homology of plasmids from different virulent strains of Agrobacterium rhizogenes. PMID- 6264522 TI - A physical and genetic map of the IncN plasmid R46. PMID- 6264523 TI - Complementation analysis in Pseudomonas aeruginosa of the transfer genes of the wide host range R plasmid R18. PMID- 6264524 TI - Purification of Escherichia coli amplifiable plasmids by high-salt sepharose chromatography. PMID- 6264525 TI - Multiple linear spiradenomas. AB - A case of eccrine spiradenoma (ESA) is described in a 35-year-old man. During an 18-year period, the original number of tumors grew in size and fused into large groups. Surgical excision of all tumors was performed successfully. The unusual features of the case were a linear distribution and giant multifocal tumors. The histology of the tumors and their appearance at the beginning and 18 years later is described. PMID- 6264526 TI - Socket reconstruction using cross-arm flaps. PMID- 6264527 TI - [Granular cell myoblastoma (author's transl)]. PMID- 6264528 TI - [Primary tracheal tumors (author's transl)]. PMID- 6264529 TI - The lung parenchymal strip as a sensitive assay for leukotriene B4. AB - Leukotriene B4 (LTB4) (3 X 10(-11) to 1.5 X 10(-9) mole; 10 ng to 500 ng) contracted the guinea-pig lung parenchymal strips in a dose-dependent manner. The contractile effect of LTB4 was not affected by methysergide (0.2 microgram/ml), propranolol (3.0 microgram/ml), phenoxybenzamine (0.1 microgram/ml), atropine (0.1 microgram/ml), diphenhydramine (0.1 microgram/ml) and FPL-55712 (1.0 microgram/ml), but was nearly completely abolished by indomethacin (20 microgram/ml). It is concluded that the contraction of the parenchymal strip to LTB4 may constitute a simple, sensitive and selective bioassay which could be either used for the determination of LTB4 in biological material or for studies on structure-activity relationship. PMID- 6264531 TI - [A mathematical model for the study of the kinetics of serum alkaline phosphatase inhibition by sodium diethyldithiocarbamate (NaDDTC)]. AB - A mathematical model for the kinetic of the serum alkaline phosphatase inhibition by NaDDTC is described in this paper. The model is tested over an experimental data set consisting on measured % residual activity of enzyme in human serum, after inhibition. The Bessey method is used. The solution of the differential equations for the model is found to be the best fitting for the observed time dependent phenomena. The rate constant, K, for the inhibition reaction is then computed. PMID- 6264530 TI - A portrait of the substrate for self-stimulation. PMID- 6264532 TI - [Medullary metastases of malignant tumors. Iconographic documentation]. PMID- 6264533 TI - [Evaluation of the ELISA method of detection "anti-cytomegalovirus" antibodies]. AB - The research of anti-Cytomegalovirus antibody by the ELISA (Enzyme-Linked Immunosorbent-Assay) test has been compared with the complement fixation method. The results have shown that ELISA test was more sensitive than the complement fixation test and easy to carry out on a large scale. PMID- 6264534 TI - [Biological effects of dithiocarbamates: changes in serum alkaline phosphatase activity "in vitro" by sodium diethyldithiocarbamate (NADDTC) (author's transl)]. AB - The Authors demonstrate that serum alkaline phosphatase (s-ALP) activity in vitro is inhibited by NaDDTC. This may be related to the NaDDTC chelating action on zinc enzyme. The trend of the phenomenon follows an exponential pattern. The activity of the isozyme pool was restored after removal from medium of NaDDTC by dialysis. The NaDDTC concentration able to inhibit in vitro enzymatic activity was nearly one thousand times higher than that found in vivo, in experimental animals (rabbit). The Authors conclude that the in vivo activity of NaDDTC in different enzymatic systems, such as ALP and other metallo-dependent enzymes, cannot be explained by its chelating action alone, but also by its influence on other systems. At present investigations in this field are in progress in our laboratory. PMID- 6264535 TI - Energy deposition by proton beams of up to 31 MeV in microscopic volumes. AB - The frequency distributions of energy deposition in microscopic volumes for proton beams of various energies and energy spreads were determined by means of a "rossi type" proportional counter. Tissue equivalent spherical volumes of 0.6, 0.72, 0.80, 1.00, 1.25, 1.50, 1.75, 2.00 micrometer diameter were simulated. Frequency distributions of energy deposition per unit pathlength are reported and their behavior as a function of the simulated pathlength, beam energy and energy spread is discussed. The results indicate that energy deposition distributions in microscopic volumes for protons in the range 8-31 MeV are skewsymmetric distributions with a tail on the high energy side, and that degraded beams behave differently from monoenergetic ones. Dose mean lineal energy values have been quoted for beams used in radiobiological experiments. PMID- 6264536 TI - Chromosome aberrations induced by protons up to 31 MeV in cultured human cells. AB - Chromosome aberrations were induced in cultured human cells by proton beams of 31, 12, and 8 MeV. The frequencies of isochromatid breaks and dicentrics have been analysed as a function of proton energy and dose. Both effects are largely dependent on proton energy; isochromatid breaks increased linearly with the dose, whereas dicentrics show a definite parabolic behaviour. The experimental data were fitted to the analytic form Y = KDn and Y = alpha D + beta D2 and the best fitted values of the parameters are reported and discussed. The values of RBE for the isochromatid breaks are in the ratio 1.7:1.3:1 for 8, 12, and 31 MeV respectively. In the case of the dicentrics the RBE values are dose-dependent function of the type CD-n. The three distributions of dicentrics among the cells do not fit a Poisson distribution. PMID- 6264538 TI - Survival and concanavalin-A-induced capping in CHO fibroblasts after exposure to hyperthermia, ethanol, and X irradiation. PMID- 6264537 TI - Absorption spectrum of DNA for wavelengths greater than 300 nm. PMID- 6264539 TI - [Effect of the radioprotectors, 2-mercaptoethylamine and 5-methoxytryptamine on the activity of reparative enzymes]. PMID- 6264541 TI - [Determination of scattered radiation and optimum discriminator adjustment of a single-channel analyzer for brain and liver scintigrams using the radionuclide (99m)Tc]. PMID- 6264540 TI - [Influencing of the rate of taking root of the tumor by L-dopa, amantadine and measles vaccine in combination with gamma radiation (author's transl)]. PMID- 6264542 TI - [Indications for lymphography in infants and children]. PMID- 6264543 TI - [Chromolymphography with a carbon-lipiodol suspension (author's transl)]. PMID- 6264544 TI - Wilms tumor: ultrasonic features, pathologic correlation, and diagnostic pitfalls. AB - The gray-scale ultrasonic features of Wilms tumor are reported with pathologic comparison. The most consistent ultrasonic features are large size, sharp margination, and echogenic heterogeneity. The frequently observed anechoic areas correlated with hemorrhage and necrosis. A rare case of mesoblastic nephroma is included for comparison. Pitfalls in diagnosis are discussed. PMID- 6264545 TI - The effect of iron on the biodistribution of bone scanning agents in humans. AB - Nine patients with chronic iron overload, resulting from either repeated transfusions or hemochromatosis, had bone scans that were characterized by a reduction of bony uptake, marked increase in renal activity, and a significant increase in soft-tissue accumulation of 99mTc-labeled bone-seeking agents. These findings were supported by semiquantitative computer analysis. The probable mechanisms of altered biodistribution and the possible role of serum ferritin are discussed. The importance of realizing the effect of excess iron on skeletal scintigraphy is further emphasized by the results of bone scanning in another patient in whom acute iron overload following infusion of iron-dextran resulted in excessive blood pool labeling. PMID- 6264546 TI - Sodium inactivation and drug-induced immobilization of the gating charge in nerve membrane. PMID- 6264547 TI - Membrane conductances of photoreceptors. PMID- 6264548 TI - Catecholamines, acetylcholine and excitability of mechanoreceptors. PMID- 6264549 TI - [Spatial dose distribution curve around the patient during the thyroid function test with 99mTc-pertechnetate (author's transl)]. PMID- 6264550 TI - Effects of 6 MeV proton on dry seeds of chloris distichophylla. PMID- 6264551 TI - [Specificity of the resistance exhibited by peritoneal macrophages of rats immunized against rubeola virus]. AB - Peritoneal macrophages in rats with no immunization against rubella virus and inoculted with bovine infectious rhinotracheitis virus are prone to suffer from a cytopathogenic effect with formation of inclusion bodies, and lysis, succeeding in reisolating the virus. The resistance of peritoneal macrophages of rats inoculated against rubella virus in nonspecific, since such resistance continues to show when macrophages interact with bovine infectious rhinotracheitis virus. The results support evidence that in the Inflammatory process suffered by rubella virus-inoculated rats, a cell immunity develops and macrophages are some of the cells performing the response. PMID- 6264552 TI - [Synthesis of cyclic AMP from renal cortex in vitro (author's transl)]. AB - The parathyroid-hormone sensitive adenylate-cyclase from renal rat cortex has been studied. Mg2+ acts as stimulator at a specific locus increasing the apparent Vmax slightly from 50 to 60 nmol of cAMP per gram of protein if the Mg2+ concentration increases from 3.25 to 16 mM, and decreases the apparent KM from 2 to 0.4 mM. Fluoride decreases the apparent KM from 5 mM in NaF concentrations of 0 to 2 mM in NaF concentrations 2 mM. Magnesium ion also decreases the apparent Ka for NaF. PMID- 6264553 TI - Guanyl nucleotide regulation of vasoactive intestinal peptide interaction with rat liver membranes. AB - This study shows the regulatory role of guanyl nucleotides on vasoactive intestinal peptide (VIP) interaction with rat liver plasma membranes. The binding of 125I-VIP to the membranes was partially inhibited by GTP and the GTP-analog Gpp(NH)p in a dose-dependent manner. This effect was mainly due to a dramatic increase of the dissociation rate of the complex tracer-membranes in the presence of guanyl nucleotides. The specificity of the binding inhibition was assessed from the lack of action of the other purine nucleotides tested. VIP stimulated cyclic AMP production in liver plasma membranes in the range 10(-10) -- 3 x 10( 7) M. Half-maximal stimulation was observed at 3 x 10(-10) M and maximal stimulation (4-fold basal value) at 10(-9) M VIP. Both GTP and Gpp(NH)p potentiated VIP-stimulated cyclic AMP production since the effect of nucleotide plus VIP was greater than the sum of the effects produced by the two agents separately. Therefore, guanyl nucleotides simultaneously inhibit the binding of VIP to its receptors and potentiate the stimulatory effect of VIP on adenylate cyclase activity in rat liver plasma membranes. PMID- 6264554 TI - Structural requirements for chelate antidotal efficacy in acute antimony(III) intoxication. AB - The LD50 for i.p. potassium antimonyl tartrate was determined to be 54.6 mg/kg in mice, with a 95% confidence range of 48.4 to 61.7 mg/kg. An examination of the antidotal efficacy of a number of different structural types of chelating agents showed that very few types were able to act as antidotes when potassium antimonyl tartrate was administered i.p. to mice at a level of 120 mg/kg. The most effective antidotes, by a substantial margin, were the water soluble vicinal dithiols: 2,3-dimercaptosuccinic acid and sodium 2.3-dimercaptopropane-1 sulfonate, with the first of these being significantly better than the second. Appreciably less effective, but still useful, was D-penicillamine. At this level of administration of antimony(III), BAL is not an effective antidote. Among other chelating agents which were also not effective at this level of antimony(III) are tartaric acid, EDTA, cysteine, sodium diethyldithiocarbamate and potassium dithiooxalate. PMID- 6264555 TI - Australian infectious bronchitis viruses: plaque formation and assay methods. PMID- 6264556 TI - Australian infectious bronchitis viruses: identification of nine subtypes by a neutralisation test. AB - The antigenic relationships between 17 Australian infectious bronchitis viruses, including six vaccine viruses, were studied by a neutralisation test using a plaque reduction method in chick embryo kidney cell monolayers. The 17 viruses formed nine distinct subtypes. Antiserum to each subtype had a high titre to viruses of the same subtype and a lower titre to viruses of different subtypes. The heterologous titres of sera varied widely. PMID- 6264557 TI - Changes in the peripheral blood leucocyte populations following an injection of corticotrophin in the immature chicken. AB - Three-week-old chickens were given an injection of corticotrophin (ACTH) (30 iu/kg) and changes in the plasma concentration of corticosterone and the numbers of peripheral blood leucocytes (PBL) were determined over a 32 hour period. Plasma corticosterone concentration increased to a peak after two hours but was within the normal range after eight hours. The PBL response was biphasic, a leucopenia after one hour and a marked leucocytosis between four and 12 hours after injection of ACTH. The leucopenia, caused by a reduction in the number of circulating lymphocytes, was significant at one and two hours; the leucocytosis was caused by a large increase in the number of polymorphonuclear cells. There were no consistent changes in the numbers of basophils, eosinophils or large mononuclear cells. PMID- 6264558 TI - Role of chemosensitivity during exercise in normal subjects and patients with pulmonary emphysema. AB - In 11 normal subjects (mean age = 22.8 years) and 8 patients with pulmonary emphysema (mean age = 70.4 years), the role of chemosensitivity in determining ventilation, cardiac output, lactic acid, and cyclic AMP and GMP was evaluated quantitatively during 150 or 30 W exercise and simulated exercise. Simulated exercise was done while the subjects took a rest by regulating arterial blood gases at exercise levels in patients and at PaO2 = 65 mm Hg and PaCO2 = 48 mm Hg in normal subjects. In normal subjects, the role of arterial blood gases in determining exercise ventilation, cardiac output, cyclic AMP and GMP are large, while those contributed much less to lactic acid. In patients, PaO2 contributed only half of the exercise ventilation. It accounted for a negligibly small portion of exercise cardiac output, lactic acid, and cyclic GMP. These results indicate, by deduction, that either augmentation of chemosensitivity, pH, or humoral factors is responsible for about half of the changes of exercise ventilation in patients with pulmonary emphysema. These factors seem to influence cardiac output, lactic acid, and cyclic AMP and GMP more strongly than PaO2 alone in exercising patients. PMID- 6264560 TI - [Adrenal response to ACTH administration in normal subjects, in patients with Addison's disease and in patients chronically treated with steroids (author's transl)]. PMID- 6264559 TI - [Adenosine cyclic monophosphate (cAMP) levels in the lymphocytes of rheumatoid arthritis patients]. PMID- 6264561 TI - [Occupational asthma (author's transl)]. PMID- 6264562 TI - [Preparation and testing of protective ointments containing Aerosil]. PMID- 6264564 TI - [Purulent tuberculous pleurisy in the clinical form of "cold pleural abscess"]. PMID- 6264563 TI - [Histogenetic classification of bronchopulmonary carcinomas and WHO histological typing]. PMID- 6264565 TI - [Value of 25-75 percent maximum expiratory flow as compared with vital capacity (ratio of MEF 25-75 to VC) in the detection of ventilatory disorders of the small air passages]. AB - The author has investigated the feasibility of DME 25--75/C.V. as a test for the detection of ventilatory disturbances of the small aerial pathways, by comparing the results with those of other tests considered to be very sensitive, such as Vmax 50% and 25% of C.V., Vmax 50% and 25% of C.V. of an air curve and that of a He-O2 mixture (80%--20%), and the isoflow volume. The study was carried out in 90 subjects, divided in two groups in relation to the values obtained by the DME 25- 75/C.V., as follows : 44 subjects with bronchial obstruction and 46 subjects showing functional signs of obstruction of the small aerial pathways. The results have indicated that the two populations classified according to this criterium are statistically different also with regard to other tests applied, indicating the feasibility of the test under study, which, compared to other tests, has the advantage of higher sensitivity in relation to the simplicity of the device. PMID- 6264566 TI - [Still current aspects of primary pulmonary suppurations]. AB - The paper presents the results of a clinical study carried out in 74 male and 11 female patients presenting with primitive pulmonary suppurations. The onset was of the acute type in 71 cases, and the radiological changes, mainly located in the right lung (in 60 patients) consisted in cavitary aspects -- frequently of the hydro-aerial type in 59 patients, and diffuse non-homogeneous opacities in the other 26. Identification of the germs responsible for the infection in the bronchial secretion maintains its significance, and facilities, with the aid of the antibiogram, an orientation of the therapy. One should stress that the Strep. aureus variety, the pyocyanic bacilli, and Klebsiella strains have determined the most severe forms of the disease. The complex therapy included administration of antibiotics. The treatment was energetic and prolonged. In 63 of the subjects penicillin perfusions were applied, while in 67 of the patients large amounts of antibiotics and sulphonamides were given simultaneously by different routes without iatrogenic effects. The persistence of radiological cavitary sequels in 40 patients (of which in 6 were of important dimensions), and the average duration of the hospitalization (38,4 days, far above the general average for the year 1979 -- 22,2 days), illustrates the difficulties in the assistance of these patients and make necessary practical measures for a rapid diagnosis in view of applying an adequate etiologic therapy, as well as the necessity for dispensarization after discharging, at least for those of the patients that still have cavitary sequelae. PMID- 6264567 TI - [Immunological mechanisms in tuberculosis]. PMID- 6264568 TI - [Immunological aspects of adverse reactions during treatment with rifampicin]. AB - It has already been established that during the treatment with rifampicin severe adverse reactions may occur, especially mediated by immune mechanisms. The most severe are those followed by renal failure. This type of reactions usually occur in patients that have undergone previous long treatments with the drug (RMP), given intermittently, twice a week, who, after an intermission, take up again the treatment with rifampicin. The symptoms occur after the administration of the first dose of the second course. Three cases are presented in the paper, of renal failure that developed after a new course of rifampicin was started. In spite of the treatment applied, which included hemodialysis, two of the patients died. In all three the indirect Coombs test was positive for anti -- RMP antibodies, and the histopathologic investigation revealed extensive lesions, including necrosis, of the renal tubules. Diagnostic, prognostic, pathogenic and therapeutic aspects of the cases are discussed. PMID- 6264569 TI - [Presence of antibodies against rifampicin in patients under tuberculostatic treatment]. AB - The study was carried out in 105 patients with pulmonary tuberculosis undergoing treatment with 900 mg of rifampicin in association with 1 or 2 tuberculostatics. The drugs were given twice weekly. Between 1 and 3 investigations were performed in each patient, using the method introduced by Poole for the detection of anti RMP antibodies. The tests were performed indifferent of the presence, or absence of clinical signs, or of biologic signs that could have suggested the development of an adverse reaction. In 34 patients (32,3%) anti-RMP antibodies were evidenced, but in only 25 of them, presenting clinical or biologicaly signs that suggested adverse reactions to rifampicin the treatment was interrupted (temporarily in 9 cases and definitively in the remaining 16). In 9 patients (8,5%) the presence of anti-RMP antibodies was demonstrated but since there were no signs of intolerance to the drug the treatment was continued. After 3--6 weeks adverse manifestations occurred also in these patients, making mandatory the definitive interruption of the treatment in 4 of them. The presence of adverse reactions without an accompanying increase in the titer of anti-RMP antibodies determined the suppression of the treatment in 3 cases. Investigation of anti-RMP antibodies has proved to be an useful method of immunological investigation, providing important data for the! interpretation of immunological mechanisms, and for the prophylaxis of adverse reactions of the immunologic type. PMID- 6264570 TI - [Differential diagnosis of tuberculosis and other diseases affecting the middle lobe of the lung (lingular lobe)]. AB - Based on data resulting from clinical, laboratory, bronchological and radiological correlations investigated in 102 patients with affections involving the median pulmonary lobe (the lingula), the author concluded that no characteristic symptoms can be evidenced, suggesting lesions of the anterior pulmonary areas. The major role in establishing the characteristics of the lesion in this area falls to the radio-bronchological investigation performed specifically for this. According to the radiological aspects the author identified 6 types of broncho-stenotic syndromes involving the median pulmonary lobe, but he stresses that in view of making an etiologic diagnosis the bronchologic investigation, and the cytohistologic study of bioptic material are of major importance. The use of immunologic test is also stressed, in the diagnosis of bronchopulmonary diseases. The author reveals that the diagnosis of "syndrome of the median lobe" cannot replace the exact diagnosis of the disease that should be made in accordance with the nomenclature of the disease and the precise indication of the nosologic form. PMID- 6264571 TI - [Experience in the centralized management of the antitubercular network in a city with a population of several million inhabitants under conditions of decreased tuberculous infections]. AB - The authors make a detailed description of the organization of detection and dispensarization of cases with pulmonary tuberculosis, as well as of extrapulmonary forms of the diseases in the city of Leningrad. The training is described, of the base network, as well as of highly specialized personnel from the research and teaching departments, and its involvement in this type of activity. As a result of the application of this method for several years, a significant reduction was noted in the incidence and the prevalence of tuberculosis in the area of the city of Leningrad. PMID- 6264572 TI - [Clinical and epidemiological significance of isolated cultures of Koch bacillus after conclusion of chemotherapy]. AB - In a group of 33 patients from the Gorj, Dolj and Mehedinti Districts positive cultures of Koch bacilli were found after various intervals following the end of chemotherapy. These positive cultures were found after negative cultures were obtained repeatedly during the usual bacteriological monitoring. The "isolated" positive culture was obtained after an interval of 11,7 +/- 8,1 months after the end of the treatment. The average number of colonies in each tube was of 3,8 +/- 3, in most of the cases (63%) there were 1--2 colonies in each tube, and in only 27% there were more than 4 colonies per tube. The development of the germs was slow and the colonies were noted 32 +/- 14 days after seeding in the Lowenstein medium. All the cases have been followed, bacteriologically as well as radiologically on the average for 16 +/- 10,9 months. Chemotherapy was not taken up again in this period. In 2 cases a new positive culture was found, and these patients were considered to have recidives, and were treated again. Of the 26 contacts under the age of 20 years 5 remained uninfected at the end of the cure and did not display allergy during the period of surveillance. None of the allergic contacts developed the disease. It is concluded that after a correct therapy the development of positive cultures during bacteriological surveillance, especially if only few colonies are noted, does not means that there is a recidive, making mandatory the sustained repetition of the bacteriological investigation without taking up again the chemotherapy. PMID- 6264573 TI - [Dynamics of the participation of different health departments in the detection of tuberculosis]. AB - The detection of new cases of tuberculosis in the territory can be achieved with efficiency with the contribution of medical dispensaries, of polyclinics, and of bed units in conditions of an integrated anti-tuberculous fight, in the frame of the current activity of the sanitary network. The integration action has a favourable influence on the participation of these units in the detection of tuberculosis. The most advanced cases have been diagnosed in the hospitals. PMID- 6264574 TI - [Feedback elements resulting from the evaluation of the efficacy, efficiency and effectiveness of integrated measures in the fight against tuberculosis. Co report]. PMID- 6264575 TI - [Dynamics of bacterial populations in experimental destructive pulmonary tuberculosis under treatment]. AB - An experimental model of cavitary tuberculosis in the animal was used, induced in rabbits, guinea-pigs or rats, and the effect of three therapeutic regimens was followed, that contained the tuberculostatics listed below: -- INH + RMP + protinamide (I); - INH + RMP + SM (II); - INH (III). In the animals that were sacrificed periodically a quantitative evaluation was made, by seeding of organ samples in culture media, of the dynamics of bacterial populations isolated at 1, 3 and 5 months after the start of the treatment. The best results were obtained with the therapeutic regimen nr. II. The association of INH to RMP leads to a rapid decrease in the number of germs. The complete recovery of the animals however was not obtained, according to histological and bacteriological criteria. PMID- 6264576 TI - [Correction of the T immunological system deficit in experimental and clinical tuberculosis]. AB - Thymus grafts, in semi-permeable chambers, from 7-10 day old white rats to guinea pigs infected with M. tuberculosis, or to white rats that had underwent thymectomy and had been infected, is accompanied by a considerable decrease in the severity of the tuberculous process. A similar effect is obtained by the subcutaneous injection of a thymus preparation called Timalin. The addition to etiotropic therapy of the immunostimulant Levamisole in amounts of 2,5 mg/kg of body weight in white rats, and of 25 mg/kg of body weight in guinea-pigs, three times during a decade significantly enhanced the effect of the conventional therapy. Levamisole, when included in the complex therapy of tuberculosis patients (three times during a decade), accelerated the detoxification process, and the recovery of recent destructive lesions in the lung. In animals and in patients Levamisole increases the low activity of the T-lymphocytes immune system, as is indicated by data obtained with the leucocyte migration inhibition test, and with the rosette-formation test. PMID- 6264577 TI - [Some difficulties in integrating the fight against tuberculosis]. PMID- 6264578 TI - [The fight against smoking as world-wide public health problem]. PMID- 6264579 TI - [Recent research in bronchopulmonary cancer]. PMID- 6264580 TI - [Model for the treatment of cases of chronic pulmonary tuberculosis in the Vilcea district]. AB - Patients with pulmonary tuberculosis are considered to be chronic cases when they continue to eliminate bacilli after one year after registration and start of treatment. The chronic cases are classified in the I B dispensary group. Following the introduction of the chemotherapy program the number of chronic patients with tuberculosis has dropped appreciably after 1974. However the rate of decrease has diminished between 1978 and 1979. In view of evaluating the possibilities for recuperation of chronic patients a research was organized in several districts. In one of them, the Vilcea District, it was noted that in spite of the fact that each year a large number of patients from group IB are eliminated, either following negativation of their sputum examinations, or by death, the total number of patients in the group itself does not decrease, since it is continuously fueled by failures of the initial treatments, and by relapses in the first two years after the end of the treatment. The analysis of the chronic cases in evidence on the 1-st of January 1980 showed that there are possibilities for recuperation by chemotherapy in 44,8% of the patients, and by surgery in another 9,5%. Only 23,8% are considered as non-recuperable. The authors review the technical and organizational measures which are indicated in view of solving the existing cases, and for the prevention of other chronicization. The short-term prognosis indicates the possibility for reducing the prevalence of chronic patients by more than 50% over a period of 3 years. PMID- 6264581 TI - [Long-term study of the evolution of chronic bronchitis detected by questionnaire 10 years earlier]. AB - The longitudinal study carried out in a group of inhabitants from Craiova showed that 16,2% of these, classified according to previously filled questionnaires as suffering from chronic bronchitis, and 10,7% of those classified as suffering from minor forms of bronchitis (sporadic symptoms) had died, and one third of them were not found when the investigation was repeated. Re-examination of 106 adults with chronic bronchitis showed that the symptoms had disappeared in two thirds of them, especially in those who gave up smoking; in 19,8% of them the symptoms had become more severe due to repeated attacks. Bronchial obstruction was present in 36% of the cases, and alterations in the small bronchial ducts were present in two-thirds of the patients. In 18-24% of the patients with minor forms of bronchitis the symptoms were more severe and chronic, and they can be classified as chronically ill patients. Frequently there were altered spirographic values. This study demonstrates that chronic bronchitis may evolve to: a) remission of the symptomatology (especially after suppression of smoking); b) more or less unmodified persistence of symptoms; c) increased severity of the symptoms following repeated acute attacks. Almost 25% of cases with sporadic coughing and expectoration became chronically ill over a period of 10 years. The questionnaire was demonstrated as having retrospective value for making a diagnosis of chronic bronchitis, but cough and expectoration are not sufficient for a differential assessment of the evolution, the spirographic data being of decisive importance. PMID- 6264582 TI - [Experiment on the partial integration of bacteriological tests for tuberculosis at several laboratories in a circumscribed area]. PMID- 6264583 TI - [Our experience in the surgical treatment of pleural empyema by thoracopleuroplasty]. AB - An analysis is presented, of the experience acquired in the Clinic for Thoracic Surgery from Bucharest in the surgical treatment of thoracal empyema by the Andrews type thoracopleuroplastia. The advantages of the surgical technique are stressed, after the modifications introduced by the authors, in contrast with other surgical techniques used, such as successive-type thoracoplastia, topographical thoracoplastia, plastron removal, etc. Careful preoperative preparation is recommended, and surgical indications are indicated and the major technical and tactical principles of the intervention are described. The Clinic's experience is based on 281 interventions. Of these 206 cases were of bacillary origin and 75 were non-bacillary. The etiologic forms of these empyemas are also analyzed. In such interventions the mortality was under 1%. Recidives were noted in approximately 1% of the cases and postoperative complications were solved without raising particular difficulties. These results recommend the thoracoplastia type intervention as the choice technique in a large number of thoracic empyemas. PMID- 6264584 TI - [In vitro action of ketoconazole on Prototheca and Fissuricella filamenta]. PMID- 6264585 TI - ["Jumping" of transposon SCTn1 on to a plasmid in Streptomyces coelicolor (author's transl)]. PMID- 6264586 TI - Appearance of chemically treated root canal walls in the scanning electron microscope. AB - The dissolving effects of seven endodontic solutions on unprepared root canal walls of young intact human premolars were evaluated with the scanning electron microscopy. After incubation at 37 degrees C in distilled water or isotonic saline for 10 min the predentinal surfaces showed no changes as compared with untreated controls. The demineralizers Decal and Largal Ultra had little effect on the organic tissues but caused some decalification where mineralized dentin was exposed. Nelex caused concentration-dependent coagulation of the residual pulp tissue, making typical ring structures on the surfaces. Sodium hypochlorite at 2.5% and 5.0% dissolved most of the predentin, exposing the globular appearance of the mineralizing front. Salvizol produced small globules on otherwise intact surfaces. Dissolution of both the organic and inorganic tissue of the root canal wall would require the combined use of two of the solutions studied. PMID- 6264587 TI - The influence of various secretory inhibitors on peptic activity. AB - The effects of pirenzepine and the H2-blocker ranitidine on pepsin secretion were studied in patients with duodenal ulcer. Pirenzepine and ranitidine in doses of 0.3 mg/kg-h inhibited pentagastrin-stimulated pepsin secretion by 63% and 82% respectively. The highest doses used of pirenzepine (0.6 mg/kg-h) and ranitidine (0.9 mg/kg-h) inhibited pepsin secretion by 69 and 93% respectively, whereas acid output was inhibited by 57 and 98%. Pirenzepine inhibited pepsin output more than hydrochloric acid output. However, pepsin output was less inhibited than hydrochloric acid output by ranitidine. These results suggest that pirenzepine might be especially useful in the treatment of those patients with peptic ulcer who have high proteolytic activity of their gastric juice. PMID- 6264588 TI - Molecular theology, immunophilosophy, and autoimmune disease. II. Speculation on the aetiology and pathogenesis of rheumatoid arthritis. PMID- 6264589 TI - Serodiagnosis of viral hepatitis A by a solid-phase radioimmunoassay specific for IgM antibodies. AB - A solid-phase radioimmunoassay for detecting specific IgM antibodies to hepatitis A virus (HAV) was developed and characterized. The test utilized microtiter plates coated with anti-IgM to specifically absorb the IgM antibodies from the test serum. The anti-hepatitis A IgM antibodies are measured by the specific consecutive binding of hepatitis A antigen and radiolabelled anti-hepatitis A antibodies (anti-HA). In 6 chimpanzees infected with HAV, IgM anti-HA was detected from about the first date of elevated transaminases and was positive for about 3 months. The usefulness of the test was confirmed by testing acute phase sera of 30 patients from a common source outbreak of epidemic hepatitis, and negative sera from 2 control groups. A collection of serum specimens from 190 patients with sporadic HBsAg-negative hepatitis in Brazil was also tested and an etiologic association with HAV was confirmed in the majority of these cases. PMID- 6264590 TI - Amoebic liver abscess probably acquired in Birmingham, England. AB - Amoebiasis is usually acquired in countries where the disease is endemic. A case is presented of hepatic infection probably acquired indigenously with identification of the source of infection. The place of dual therapy for treatment is considered and the value of ultrasound scanning in management illustrated. PMID- 6264591 TI - Head-space gas chromatography as a tool in the identification of anaerobic bacteria and diagnosis of anaerobic infections. AB - The identification of anaerobic bacteria to the species level can be a laborious and time consuming procedure. Gas chromatography offers a diagnostic aid, and the advantages of the recently introduced head-space gas chromatography technique are: it is rapid, accurate and easy to perform; it provides more information of differential diagnostic value; and the identification process can be automated by connecting the head-space gas chromatograph to an automatic injection unit and a computer which interprets the chromatograms. The head-space technique may be used for direct analyses of clinical specimens for rapid diagnoses of anaerobic infections. PMID- 6264592 TI - Hereditary pyrophosphate arthropathy. PMID- 6264593 TI - Sensory neuropathy in rheumatoid arthritis: an electroneurographic study. AB - In a selected series of twenty-three RA patients, aged from 23 to 56 years, mean 41, the neurophysiological functions of six sensory nerves were measured and the results were correlated with clinical and laboratory data. Significant changes in the functions of one or more nerves were found in 10 patients, 2 of whom had no symptoms of clinical neuropathy. There was a highly significant correlation between neurophysiological symptoms and clinical neuropathy symptoms, although the combination of the clinical and electrophysiological findings was variable. On the other hand, there was no significant correlation between neurophysiological/neurological findings and clinical/laboratory data (age, sex, duration of disease, stage of disease, rheumatoid factor and erythrocyte sedimentation rate). Manifest or sub-clinical mono-neuropathies in n. medianus were found in 5 patients. In the light of these results it would seem in order to recommend the inclusion of an electro-neurophysiological examination of the medianus nerves of RA patients in routine diagnostic procedures. PMID- 6264594 TI - Studies on synthesis and relationship between analgesic activity and receptor affinity for 3-methyl fentanyl derivatives. AB - In the present paper, the synthesis and analgesic activity (mice, i.p. hot plate test) of the derivatives of 3-methyl fentanyl are briefly described. Compound 7302, cis-N-[1-(2-hydroxy-2-phenylethyl)-3-methyl-4-piperidyl]-N phenylpropionamide (cis: 3-methyl/4-N-phenylpropionamide) is found to be the most potent analgesic agent in this series synthesized by our laboratory (ED50 = 0.0022 mg/kg). The analgesic activity of 7302 is 28 times more potent than that of fentanyl and 6300 times more than that of morphine. The partition coefficients of 10 compounds in the series are determined by high performance liquid chromatography (HPLC) and their log p values are about 3. There are no regular relationships between the analgesic activity and partition coefficients. Study on the specific binding of 8 out of the above 10 compounds to crude synaptic plasma membrane (P2-fraction) of mouse brain demonstrates that there is an excellent statistical linear correlation (r = 0.998) between the analgesic potency and the specific binding affinity. The result shows that the analgesic potency of the derivatives of this series is mainly dependent on binding affinity for opiate receptor. PMID- 6264595 TI - Dissections and reconstructions of genes and chromosomes. PMID- 6264597 TI - Epidermal growth factors enhances viral transformation of granulosa cells. AB - Kirsten sarcoma virus produced a low incidence of transient morphological transformation in primary cultures of rat ovarian granulosa cells. In the presence of epidermal growth factor, the incidence of transient transformation increased severalfold and two continuous cell lines were established. Epidermal growth factor, a naturally occurring polypeptide hormone, appears to act here as a tumor promoter in the retrovirus-induced transformation of a mesodermally derived epithelium. PMID- 6264596 TI - Warburg effect revisited: merger of biochemistry and molecular biology. PMID- 6264598 TI - Three distinct genes in human DNA related to the transforming genes of mammalian sarcoma retroviruses. AB - Southern blot hybridization was used to identify human and other vertebrate DNA sequences that were homologous to cloned DNA fragments containing the oncogenic nucleic acid sequences of three different type C mammalian retroviruses (simian sarcoma virus, the Snyder-Theilen strain of feline sarcoma virus, and the Harvey strain of murine sarcoma virus). Each onc gene counterpart has a single genetic locus, which probably contains non-onc intervening sequences. The human DNA sequences may represent genes important to cell growth or cell differentiation, or both. Their identification and isolation may allow elucidation of their role in these processes and in neoplasias. PMID- 6264599 TI - Biology of hepatitis B virus. AB - Immunochemical investigations of the viral antigens and molecular characterization of the viral DNA have elucidated the nature of the hepatitis B virus infection underlying acute, chronic, and oncogenic disorders of the liver in man. Cloning and sequencing of viral DNA have made possible studies on the structure of the genome and on certain aspects of the biology of the virus, hitherto constrained for a lack of tissue culture systems and laboratory animal models useful in its propagation. PMID- 6264600 TI - Inserted sequences in bovine satellite DNA's. AB - The nucleotide sequence of the 1413-base-pair repeat unit of bovine 1.711a satellite DNA (density in cesium chloride, 1.711 grams per cubic centimeter) has been determined. The repeat unit contains two segments consisting of variants of a basic 23-base-pair sequence that is closely related to sequences of bovine 1.706 satellite DNA. A third segment of the repeat unit contains an unrelated 611 base-pair sequence that is not internally repetitive. This segment is flanked by inverted repeats of 8 base pairs and, on one side, by a direct repeat of the terminal sequence. A related segment is present in bovine 1.711b satellite DNA and is inserted into sequences derived from the 1.715 satellite. These nucleotide sequences suggest the timing of some of the stages in the evolution of these complex, closely related satellite DNA's and indicate the mechanisms inherent in their divergence from a common ancestor. PMID- 6264601 TI - Viral epitopes and monoclonal antibodies: isolation of blocking antibodies that inhibit virus neutralization. AB - The inability of pathogenic animal viruses to be completely neutralized by antibodies can lead to chronic viral infections in which infectious virus persists even in the presence of excess neutralizing antibody. A mechanism that results in this nonneutralized fraction of virus was defined by the topographical relationships of viral epitopes identified with monoclonal antibodies wherein monoclonal antibodies bind to virus and sterically block the binding of neutralizing antibodies. PMID- 6264602 TI - Glucoreceptors controlling feeding and blood glucose: location in the hindbrain. AB - Microinfusion of 5-thioglucose into either the lateral or fourth cerebral ventricle caused increased feeding and hyperglycemia in rats when the cerebral aqueduct was unobstructed. If the aqueduct was obstructed and 5-thioglucose was infused into the fourth ventricle, increased feeding and hyperglycemia persisted, whereas feeding and hyperglycemia in response to lateral ventricle infusion were abolished. Drinking in response to infusion of angiotensin II into the lateral ventricle was not diminished by aqueduct obstruction. These results indicate that glucoreceptors that mediate feeding and hyperglycemia in response to cerebral glucoprivation are located in the caudal hindbrain and not in the hypothalamus where they have previously been sought. PMID- 6264604 TI - Epileptogenic agents enhance transmission at an identified weak electrical synapse in Aplysia. AB - To examine the possibility that alterations in the effectiveness of electrical synapses might participate in epileptogenesis, the effects of several convulsants on an identified weak electrical synapse in Aplysia were examined. Application of pentylenetetrazole, strychnine, or tetraethylammonium led to a dramatic increase in the size of the electrical postsynaptic potential mediated by the synapse; penicillin was considerably less effective. In a number of animals, the increased electrical synaptic effectiveness led to the abnormal conduction of spikes across the synapse. If convulsants have a similar action in mammalian cortex, enhanced transmission at weak electrical synapses may provide abnormal pathways for the flow of seizure activity and contribute in part to the synchronous firing of neurons characteristic of epileptic activity. PMID- 6264603 TI - Calcitonin messenger RNA encodes multiple polypeptides in a single precursor. AB - Recombinant DNA techniques were used to analyze the structure of the messenger RNA encoding a precursor of calcitonin, a small calcium-regulating hormone of 32 amino acids. Analyses of the nucleotide sequences of cloned complementary DNA's comprising the entire coding sequence of the messenger RNA revealed that calcitonin is flanked at both its amino and carboxyl termini by peptide extensions linked to the hormone by short sequences of basic amino acids. The location of glycine next to the carboxyl terminal prolinamide of calcitonin is consistent with indications that glycine is required for the enzymatic amidation of proline to the prolinamide. During cellular biosynthesis, calcitonin arises from a large precursor protein by cleavages at both amino and carboxyl terminal residues of the hormone. These findings raise questions concerning the regulation of these cleavages and the potential biological functions of the precursor extensions derived from these cleavages. PMID- 6264606 TI - Plasmid DNA in Treponema pallidum (Nichols): potential for antibiotic resistance by syphilis bacteria. AB - A plasmid DNA structure (approximate molecular weight = 7.5 X 10(6)) was identified in the human pathogen Treponema pallidum (Nichols). The inability to isolate this plasmid from rabbit host tissue and the total lack of DNA homology of the plasmid with rabbit DNA has confirmed its Treponema pallidum origin. The observation documents a newly recognized and potentially significant genetic capability for Treponema pallidum. PMID- 6264605 TI - Benzodiazepine inhibition of the calcium-calmodulin protein kinase system in brain membrane. AB - Benzodiazepines inhibit Ca2+-calmodulin-stimulated membrane protein phosphorylation. The effects of the benzodiazepines on protein phosphorylation are stereospecific and produced by membrane-bound benzodiazepine. The potency of benzodiazepine kinase inhibition is correlated with the ability of the benzodiazepines to inhibit electric shock-induced convulsions. These findings provide evidence that some of the anticonvulsant and neuronal stabilizing effects of benzodiazepines may be modulated by the Ca2+-calmodulin protein kinase system and indicate that this calmodulin-kinase system represents an identifiable benzodiazepine receptor in brain that is distinquishable by several criteria from the previously described high affinity benzodiazepine receptor. PMID- 6264607 TI - Delta9-tetrahydrocannabinol increase plasma testosterone concentrations in mice. AB - Oral administration of delta 9-tetrahydrocannabinol had a biphasic effect on plasma testosterone concentrations in male mice, causing rapid sustained increases at low doses and subsequent decreases at higher doses. In hypophysectomized and intact mice receiving gonadotropins (human chorionic gonadotropin), treatment with delta 9-tetrahydrocannabinol maintained higher plasma testosterone concentrations. Thus, this cannabinoid may interact with gonadotropin and directly influence testicular steroidogenesis in vivo. PMID- 6264608 TI - Tolerance and cross-tolerance in chronic alcoholics: reduced membrane binding of ethanol and other drugs. AB - Membrane binding of ethanol, anesthetics, and hydrophobic molecules in brain synaptosomes and liver mitochondria from rats is conspicuously reduced after long term consumption of ethanol. The membranes are resistant to structural disordering by both ethanol and halothane. Tolerance, cross-tolerance, and dependence in chronic alcoholics may in part result from membrane alterations that inhibit the binding of ethanol and other drugs. PMID- 6264609 TI - [Primary sclerosing cholangitis. Report on three cases (author's transl)]. PMID- 6264610 TI - [Carcinosarcoma of the stomach (author's transl)]. PMID- 6264611 TI - [Inflammatory pseudo-tumors of the stomach. Report of a case (author's transl)]. PMID- 6264612 TI - [Perianal mucinous adenocarcinoma (author's transl)]. PMID- 6264613 TI - [Demons-Meigs' syndrome associated with a seminoma of ovary (author's transl)]. PMID- 6264614 TI - [Cineradiological study of the activity of sorbiperan on the gallbladder and colon (author's transl)]. AB - The activity of sorbiperan was assessed during radiological examinations of 15 patients with hypomobility of the gallbladder, associated in some cases with atonic dyspepsia, and 25 cases of spastic colon with constipation and/or diarrhea due to diverticulosis, dolichocolon, sigmoiditis, or parasitosis. Patients with gallbladder dysfunction were examined radiologically before and after oral administration of 20 to 40 ml of sorbiperan, the dose varying as a function of bodyweight. In 3 patients, the hypermobility of the gallbladder provoked by this agent was greater than that observed with all usually employed products, in 11 cases the cholagogue produced an excellent effect, while in one case there was no observed effect. Patients with colitis were administered a barium enemea, and an initial series of films were taken. These were repeated after addition of 80 ml of sorbiperan to the same enema. Total, rapid evacuation of the colon was observed in 8 cases, while in 15 cases it was of excellent quality. No effect was noted in 2 cases. Sorbiperan provokes effective contractions of the gallbladder, favours sphincter of Oddi dynamics, increases motility of all digestive tract segments, and very significantly accelerates gastro-entero-colic peristalsis. Tolerance was excellent. PMID- 6264616 TI - [Total prosthesis for major arthrosis sequelae of congenital dislocation of the hip (author's transl)]. AB - The author reports his personal experience with the use of total hip arthroplasty in 48 adult patients with major arthrosis sequelae from congenital dislocation of the hip. Particular emphasis is laid on a description of a classification of these sequelae, the technique used for total prosthesis application, and the results obtained, which are the consequence of close cooperation between the members of the surgical team, and the way in which the technique performed has been improved over the course of the years. PMID- 6264615 TI - [Serum urate and gout in 4663 young male workers (author's transl)]. AB - Serum urate levels and history of gout were observed from 4663 men aged 20-44 who were employed by a Parisian government agency. Serum urate levels, mean value 62,8 mg/l (374 mu mol/l), did not vary with age but were strongly correlated with weight. For constant weight, urate levels decreased with age. By our definition: typical history of gout and either efficacity of colchicine during an attack or serum urate level over 70 mg/l (417 mu mol/l) at examination, there were 57 cases of gout, giving a prevalence of 1,1% among men 35-39 and 2,0% among men 40-44 years old. Using the definition by the New York criteria which do not include serum urate level, there were 51 cases of gout, giving a prevalence of 1,5% in the 35-44 year age group. This is about 3 times the prevalence found by O'Sullivan, using the same criteria, in an American town. the higher serum urate levels in the present study may account for much of this difference. The incidence of new cases of gout was estimated to be 1,6% over 5 years for men 40 44 years old. The site was the great toe in 57% of gouty men with only one attack and in 92% of those with more than one attack. It was not related to the amount of standing or activity at work. Comparison with a study made 7 years earlier showed an augmentation in serum urate values and probably in prevalence of gout. These results are discussed in terms of dietary modification over this time period. PMID- 6264617 TI - [Primary linitis plastica carcinoma of the colon and the rectum. Report of three personal cases (author's transl)]. AB - Primary linitis plastica carcinoma of the colon is rare. Only 19 cases have previously been described in the american literature and three french cases are reported. Clinically, this entity appears as an inflammatory lesion. It revolves to a stenotic lesion and death by metastases. Eighty-four per cent of carcinomas are beyond the splenic angle and sixty-six per cent are localized on rectum or distal sigmoid. These tumours are accessible to rectoscopic examination and biopsy which is the only examination able to assert the diagnosis of linitis. Histologically, nothing can distinguish a primary colonic localization from a metastasis. Therefore, it is very important to search for a primary localization especially gastric. Surgical resection is efficient with or without X ray-therapy as we have seen it with control of carcino-embryogenic antigene evolution in one of our cases. Prognosis is bad, especially among people over 50 years with metastasis. PMID- 6264618 TI - [Tracheal dyskinesia (tracheomalacia) in infants and children. Study of 127 cases diagnosed through endoscopic examination (author's transl)]. AB - 127 cases of tracheal dyskinesia were seen in infants and children out of which 87 were 1 to 12 months of age. The diagnosis was based on the existence of a collapse reducing the tracheal diameter of more than 50% on endoscopy. Endoscopic examination was performed without general anesthesia. This material represents 5,8% of the patients submitted to this procedure. 85 patients had "primitive" dyskinesia and 42 had major associated abnormalities. Uni or bilateral bronchial dyskinesia was associated in 43% of the cases. The four commonest presenting symptoms were a stridulous or wheezing respiration, recurrent bronchitis, chronic cough, cyanosis. The frequency of associated digestive troubles: gastroesophageal reflux aspiration was noteworthy. Several functional consequences were encountered: hypoxemia, hypercapnia, abnormalities of FRC, increased RL, lowering of dynamic compliance, alterations of perfusion and ventilation on scintiscans. The prognosis was good in primitive cases. Two deaths occurred, in the group with associated abnormalities. The pattern of the patient with primitive dyskinesia and that of the patient with dyskinesia and associated abnormalities are outlined. Some features remarkable in this series of patients are pointed out in a discussion of the pathophysiology of the syndrome. Increased transmural pressure is not a common cause of tracheal dyskinesia and infection as well. The possibility of a temporary intrinsic anomaly of the tracheal wall is suggested. Even if its exact mechanism remains unknown, tracheal dyskinesia is a distinct entity observed in infants and children. It appears as a common cause of recurrent bronchopulmonary disease in the young. PMID- 6264619 TI - [The value of mammary thermography. A report on 655 cases (author's transl)]. AB - A total of 655 patients were investigated by both mammography and contact thermography, and 63 cancers of the breast were detected. Thermography was slightly more sensitive (0.82) than mammography (0.75). They were of equal specificity (0.96 and 0.97). A critical analysis of the experimental conditions, however, leads the authors to propose thermography as the essential investigation completing clinical examination and mammography. It may also have a certain prognostic value, but this remains to be demonstrated. PMID- 6264620 TI - [Ulcerative colitis in Behcet's disease (author's transl)]. PMID- 6264621 TI - [Purulent anaerobic pericarditis: report of a case and review of the literature (author's transl)]. PMID- 6264622 TI - [A rare etiology of portal hypertension in an adult: congenital hepatic fibrosis. Review of current literature in connection with an observation (author's transl)]. AB - On the basis of a personal observation the authors review the current literature on the hypertensive forms of congenital hepatic fibrosis found in an adult subject during G.I. haemorrhage through the rupture of gastro-oesophageal varices. These observations seem to be exceptional and 17 cases were recorded between 1956 and 1976. A complete hemodynamic portal study was carried out only in six cases. It shows a presinusoidal portal hypertension in three cases, post sinusoidal or sinusoidal portal hypertension in two cases, mixed hypertension in one case. Our observation is outstanding because of the existence of a rise of the wedged hepatic venous pressure varying from one hepatic vein to the other. The prognosis seems to be relatively bad for the short-term as the mortality rate of 2 years reaches at least 29%. PMID- 6264623 TI - [Rapid disappearance of calcification in a case of multiple tendinous calcifications (author's transl)]. AB - The authors describe a case of multiple tendinous calcification which was of unusual interest because of its localization (left gluteus medius tendon), the associated fever, its rapid favourable evolution (72 hours), and the disappearance of radiological signs of calcification. PMID- 6264624 TI - [Male pseudohermaphroditism. State and present problems (author's transl)]. AB - The authors describe the male phenotypic sexual development in the fetus: transformation of the undifferentiated gonad into testis under the HY antigen influence; testicular secretion of testosterone (which allows the development of the wolffian ducts derivatives) and of MIF (which inhibits the development of the mullerian duct; masculinization of the external genitalia under the influence of dihydrotestosterone. They outline the three abnormalities which may lead to a male pseudohermaphroditism: disorders of testicular differentiation, defects of testicular function and androgen insensitiveness at the target areas. They consider the diagnostic steps and the therapeutic management especially in relation to the choice of the sex and the risk of gonadoblastoma. PMID- 6264625 TI - Particle radiation therapy: the first forty years. PMID- 6264626 TI - Future prospects of radiation therapy with protons. PMID- 6264627 TI - Sensitizers and protectors in clinical oncology. PMID- 6264630 TI - Choosing among therapies: illness behavior in the Ivory Coast. PMID- 6264629 TI - Review of Wilms' tumour in Malaysian children. PMID- 6264628 TI - The integration of tumor associated antigens in cancer management. PMID- 6264631 TI - Wilms' tumor in an adult. AB - We have described an adult with Wilms' tumor treated with surgery, radiotherapy, and chemotherapy. Although the patient responded initially, he died 17 months after diagnosis. A review of the literature in English disclosed only six other adults with Wilms' tumor similarly treated. Only two were long-term survivors, both treated with combination chemotherapy and radiation therapy. Adult Wilms' tumor is rare and carries a more pessimistic prognosis than in children, but it is responsive to radiation and combination chemotherapy. PMID- 6264633 TI - [Latency of the herpes simplex virus and nervous system diseases]. PMID- 6264632 TI - Glycogenosis type IB: possible membrane transport defect. AB - We have described a 20-month-old child with type IB glycogen storage disease, based on clinical and biochemical manifestations. Functional testing data were similar to those found in glucose-6-phosphatase deficiency, but in vitro studies showed normal hepatic glucose-6-phosphatase activity. Disruption of membranes with deoxycholic acid was followed by an increase in enzyme activity compared to a control liver tissue, suggesting "latency" of enzyme. We suggest that this patient had glycogen storage type IB and that this disorder may represent a specific glucose-6-phosphate transport defect. PMID- 6264634 TI - [Iruxol treatment trials in suppurative wounds]. PMID- 6264635 TI - Motor function of the extramural portion of the canine common bile duct. PMID- 6264636 TI - Multiple spinal arachnoid cysts: the role of oily contrast medium. PMID- 6264638 TI - Unilateral proptosis secondary to a retroorbital tumor: fibrous histiocytoma or xanthogranulomatous lesion. PMID- 6264637 TI - VM-26 monochemotherapy trial in the treatment of recurrent supratentorial gliomas: preliminary report. AB - Twenty-five adults with recurrent supratentorial malignant gliomas were treated with VM-26 in a monochemotherapy schedule, the antiblastic region covering a period of 24 weeks. Five cases were excluded from the final evaluation, 4 because of protocol violations and 1 due to intolerance to the drug. In the group of 20 patients who met the criteria for evaluation, 7 (35%) showed a partial or complete response, with clinical or radiological tumor aggression, and the conditions of 7 (35%) were unchanged at the end of the chemotherapy courses. The progression-free intervals turned out to be 10.4 months and 8.5 months, respectively. Six patients (30%) complained of tumor progression despite the treatment. Most of the patients are still alive, and the actuarial survival rate is encouraging. Toxicity was mainly hematologic, but usually moderate and easily reversible. PMID- 6264639 TI - Calcifications in pituitary adenomas. AB - In a surgical series of 755 pituitary adenomas, 51 cases (6.75%) showed intratumoral calcifications on microscopic examination and 13 of these were visible on roentgenographic examination (1.72%). Thirty-eight of these 51 cases were prolactinomas, the highest incidence being in male patients. There was no correlation between age, sex, levels of hormone, size of the tumor, and the presence of calcifications. Four patterns of radiological calcifications were encountered. Histologically, the calcifications were most frequently found within the tumor masses. Their rare occurrence within fibrous or degenerative areas speaks against their dystrophic nature. Previously reported calcified bodies in fetal and newborn pituitaries and the recently described physiological hyperprolactinemia in early infancy suggest a possible hormonal influence in the genesis of calcifications in prolactinomas. PMID- 6264640 TI - Cytomegalovirus infection: a quantitative prospective study of three hundred twenty consecutive renal transplants. AB - The quantitative effects of cytomegalovirus (CMV) infection on morbidity and mortality rates were examined in 320 renal transplant cases. With the use of virus cultures and CMV antibody measurements, all patients were studied, regardless of symptoms, from a time before transplantation to at least 1 year, 11 months after transplantation for a maximum of 5 years, 9 months. The posttransplant risk factors of CMV infection--patient age, type of donor (living related or cadaver), antigen match between donor and recipient, presence of diabetes, and the presence of pretransplant CMV antibody--were evaluated for their relative effects on patient survival, graft survival, fever, and leukopenia. CMV infection was a significant risk factor for these four events. CMV infection occurred in 181 patients after transplantation and accounted for 25% of the deaths, 20% of the graft failures, 30% of the occurrences of fever, and 35% of the occurrences of leukopenia. Unexpectedly, female recipients were at higher risk than men for the adverse effects of CMV infection. Young patients and those receiving their second transplant were at higher risk of graft loss if they had associated CMV infection. CMV infection was most reliably predicted by the presence of pretransplant antibody, indicating that reactivation of endogenous virus was responsible for most infections. The presence of pretransplant antibody offered a small amount of protection against fever, but no protection against death, graft failure, or leukopenia. Simultaneous episodes of CMV infection and transplant rejection, both common posttransplant events, most often occurred by chance. PMID- 6264641 TI - Abdominal wound closure--a comparison of monofilament nylon and polyglycolic acid. AB - The incidence of burst abdomen, incisional herniation, and sinus formation after a vertical abdominal incision was studied in a prospective randomized trial that compared two suture materials--monofilament nylon and polyglycolic acid. Laparotomy wounds were closed with a continuous mass suture technique. Of the 210 patients studied, 15 died between 10 days and 6 months postoperatively with their wounds intact. The remaining patients were followed up for 6 months or longer. The two groups were well matched for known risk factors. The 104 patients in the polyglycolic acid group had a 12.5% wound failure rate (1 burst abdomen and 12 hernias), but the 106 patients in the nylon group had only a 4.7% wound failure rate (1 burst abdomen and 4 hernias) (P = 0.04). There was a significant association between the rate of infection and sinus formation, but there was no difference between the incidence of these complications between the two groups. Closure of abdominal wounds with absorbable sutures does not appear to be justified, and we suggest that nylon and the mass closure technique be used for all abdominal wound closures. Other etiologic factors significantly associated with wound failure include male sex and postoperative chest complications. However, infection remains the most significant postoperative complication because the incidence of incisional hernias and sinus formation would be reduced by the elimination of wound sepsis. PMID- 6264642 TI - Granular cell myoblastoma of the esophagus. AB - Twenty-seven cases of granular cell myoblastoma of the esophagus have been reported. We describe two additional cases. The clinical aspects are analyzed briefly. Although the malignancy potential is low, invasion does occur, and these lesions should be removed. PMID- 6264644 TI - Uptake of radiolabeled leukocytes in prosthetic graft infection. AB - The utility of radionuclide labeled leukocytes in the demonstration of infection within vascular prostheses was examined. The infrarenal aorta was replaced with a 3 cm Dacron graft in 12 dogs. On the third postoperative day, six of the animals received an intravenous injection of 10(8) Staphylococcus aureus. Labeled leukocyte scans were performed at postoperative days one and three, and then weekly for 8 weeks with indium-111 and technetium-99 labeled autologous leukocytes. When scans showed focal uptake of isotope in the area of prosthetic material, the grafts were aseptically excised and cultured on mannitol-salt agar. Both control and infected animals had retroperitoneal isotope activity in the immediate postoperative period that disappeared by the end of the first week. By the eighth postoperative week, all of the animals that received the bacteremic challenge had both radionuclide concentration in the region of the vascular prosthesis and S. aureus cultured subsequently from the perigraft tissues. None of the control animals had either radionuclide or bacteriologic evidence of infection at the eighth postoperative week. The radiolabeled leukocyte scan is a highly sensitive and specific technique, clinically applicable for the diagnosis of vascular prosthetic infections. PMID- 6264643 TI - Hemodynamic study of ischemic limb by velocity measurement in foot. AB - By means of a tracer technique with 99mTc-pertechnetate, provided with seven zonal regions of interest, 6 mm in width, placed at equal spaces of 18 mm, from the toe tip to the midfoot at a right angle to the long axis of the foot, arterial flow velocity in the foot during reactive hyperemia was measured. The mean velocity in the foot was 5.66 +/- 1.78 cm/sec in 14 normal limbs, 1.58 +/- 1.07 cm/sec in 29 limbs with distal thromboangiitis obliterans (TAO), 0.89 +/- 0.61 cm/sec in 13 limbs with proximal TAO, and 0.97 +/- 0.85 cm/sec in 15 limbs with arteriosclerosis obliterans (ASO). The velocity returned to normal in all 12 limbs after successful arterial reconstruction, whereas the foot or toe blood pressure remained pathologic in 9 of the 12 limbs postoperatively; the velocity reverted to normal in 4 of 13 limbs after lumbar sympathectomy. When the velocity was normalized after operation, the ulceration healed favorably, and the ischemic limb was salvaged. The most characteristic feature of peripheral arterial occlusive disease of the lower extremity was a stagnation of arterial circulation in the foot, and the flow velocity in the foot was a sensitive predictive index of limb salvage. PMID- 6264645 TI - [General activity and isoenzyme spectrum of cytochrome oxidase and malate dehydrogenase in acute and chronic pneumonia with different degrees of inflammation]. PMID- 6264648 TI - [Quackery and alternative therapeutic methods]. PMID- 6264647 TI - An in vivo/in vitro evaluation of teratogenic action. AB - Several compounds were administered to pregnant Wistar-derived rats either 24 or four hours prior to the recovery of day 10 embryos for in vitro culture in Waymouth's medium and fetal calf serum. The compounds tested were 2-amino-1,3,4 thiadiazole (thiadiazole), cadmium sulfate, 1,2-dibromo-2,2-dichloroethyl dimethyl phosphate (dibrom), 2-(sec-Butyl)-4,6-dinitrophenol (dinoseb), led nitrate, polybrominated biphenyls (PBB), sodium arsenate, and trypan blue. After 24 hours in culture, two thirds of the embryos were recovered for examination. The remaining one third were continued in culture until 42 hours. Recovered embryos were examined for rotation of the embryonic axis, heart rate, establishment of the visceral yolk sac circulation, somite number, growth of the limb buds, closure of the neural tube, and development of the allantois and amnion. All tested compounds inhibited the rate of development in vitro. PMID- 6264646 TI - [Lung cancer metastasis into the supraclavicular and cervical lymph nodes in relation to the primary site of the tumor]. PMID- 6264649 TI - Dermal contact with toluene diisocyanate (TDI) produces respiratory tract hypersensitivity in guinea pigs. PMID- 6264650 TI - Analysis of aflatoxin B1 in human tissues with high-pressure liquid chromatography. PMID- 6264651 TI - Comparison of the effectiveness of several chelators after single administration on the toxicity, excretion, and distribution of cadmium. PMID- 6264652 TI - Perinatal exposure to cannabichromene and delta 9-tetrahydrocannabinol: separate and combined effects on viability of pups and on male reproductive system at maturity. AB - The effects of cannabichromene (CBC), delta 9-tetrahydrocannabinol (delta 9-THC) and their combination (all doses 50 mg/kg orally) were determined after being administered to female mice for 7 days beginning on the 20th day of gestation. The THC treatment reduced postnatal viability, impaired male reproductive behavior at maturity and significantly reduced seminal vesicle weights. No changes from control values occurred after CBC or CBC + THC. Thus, CBC alone at this dosage did not act like THC; moreover, it antagonized the effects of THC when the two were given in combination. PMID- 6264653 TI - A quantitative assay system for thymocyte regeneration in the rat. PMID- 6264654 TI - [Combined chemotherapy and radiotherapy of small cell carcinoma of the lung]. PMID- 6264655 TI - In vivo evaluation of calcium-loaded zeolites and urease for urea removal in hemodialysis. PMID- 6264656 TI - Geographic and family studies of immunological responses to antigens of the murine mammary tumor virus in sera of patients with breast cancer. AB - Sera of breast cancer patients from the United States, India, East Africa and China as well as from their families and from healthy women were assayed for antibodies reactive with the murine mammary tumor virus (MuMTV). Detection was by an enzyme-linked immunoassay recently developed in our laboratory. In the women with breast cancer, 62% of the East Africans, 28% of the Indians, 19% of the Americans but only 5% of the Chinese had antibody to MuMTV. Among healthy women, 21% of the Africans, 3% of the Americans and 5% of the Chinese possessed this antibody. Several family members of breast cancer patients, males as well as females, had increased levels of MuMTV antibody. The MuMTV-reactive antibody was removed by absorption with MuMTV, deglycosylated MuMTV and gp52, the major MuMTV envelope protein. It was not absorbed out by murine leukemia viruses, red blood cells from various species, fetal calf serum or carbohydrates. The results suggest that there may be more than one form of breast cancer, definable by reactivity to MuMTV. The murine mammary tumor virus (MuMTV) is the etiological agent of breast cancer in mice. The induction of mammary tumorigenesis, however, is dependent upon the genetic makeup, hormonal status, and diet of the infected mouse. Thus, even in a situation where a known single cause for breast cancer exists, disease manifestation is subordinate to diverse factors in the individual host. PMID- 6264657 TI - Mechanism of intermittent glomerular perfusion in the rat. PMID- 6264658 TI - Immunoregulatory functions of cultured human T lymphocytes. AB - Twenty continuous cultures of human T cells (CTC) (15 from normal individuals and five from patients with T cell malignancy) growing in the presence of PHA stimulated lymphocyte conditioned medium were studied for their ability to participate in the regulation of the in vitro immunoglobulin (Ig) production induced by five polyclonal activators, pokeweed mitogen (PWM), Epstein-Barr virus (EBV), Nocardia opaca water-soluble mitogen (NWSM), streptolysin O (SLO), and staphylococcl phage lysate (SPL). The CTC did not produce significant amounts of Ig in the presence of any polyclonal activator. One out of 15 CTC examined showed helper activity of moderate degree when co-cultured with B cells rigorously depleted of T cells in PWM-driven Ig biosynthesis. Two of the other CTC helped minimally. Nine of 20 CTC examined (8 of 15 from normal individuals and 1 of 5 from patients with T cell malignancies) were found to have marked suppressor cell activity when co-cultured with normal lymphocytes in the PWM-induced Ig production system and four had moderate or variable suppressive effect. This suppression was apparently not due to simple "overgrowth" or nonspecific toxic effects of CTC because (1) the CTC did not proliferate when cultured without conditioned medium, (2) the CTC did not suppress Ig production when they were added 3 days after the beginning of the 12-day cultures, (3) the CTC did not show cytotoxic activity against normal T and B cells, and (4) the CTC did not inhibit tritiated thymidine incorporation into PWM- or EBV-stimulated lymphocytes when mixed with them at the onset of culture. Ig production induced by EBV or NWSM, which are relatively T cell-independent polyclonal activators, was suppressed significantly T cell-independent polyclonal activators, was suppressed significantly by only one out of nine and one out of six CTC examined, respectively. Four clones produced by a limiting dilution method from one suppressor CTC suppressed PWM-driven Ig synthesis as markedly as the uncloned suppressor CTC. Such CTC may be of considerable value in studies of the mechanisms involved in the regulation of immunoglobulin biosynthesis and in the preparation of antisera to T cell subsets. PMID- 6264659 TI - Coupling between H+ transport and anaerobic glycolysis in turtle bladder. Vanadate sensitivity of H+ pump. PMID- 6264660 TI - Identification of two distinct adenosine diphosphate receptors in human platelets. AB - (1) FSBA, an inhibitor of platelet shape change and aggregation, inhibits and reverses the binding of fibrinogen to washed platelets induced by ADP in the presence of calcium ion; (2) FSBA does not inhibit either aggregation of or fibrinogen binding to platelets treated with chymotrypsin; (3) additional evidence is provided that FSBA does not inhibit aggregation by stimulating cyclic AMP accumulation; (4) FSBA does not inhibit PGE1-induced cyclic AMP accumulation and has little ability to inhibit the action of ADP on cyclic AMP or the binding of the ADP analog [beta 32P] 2-MeSADP; and (5) these results provide additional support for the view that the effects of ADP on aggregation and on cyclic AMP are mediated by distinct receptors, one of which, designated "A", is labeled by FSBA; the second receptor designated "C", has selective affinity for 2-MeSADP. PMID- 6264661 TI - The George M. Kober lecture. "Cushing's syndrome--1980.". PMID- 6264662 TI - Investigations concerning the cultivation of myxo- and paramyxoviruses on chorioallantoic membrane fragments. Note I. Data on the multiplication of several myxo- and paramyxoviruses. AB - Influenza viruses A(H1N1) and A(H3N2) and parainfluenza viruses (Sendai mumps) were cultivated in chorioallantoic membrane (CAM) fragments maintained in media with different formulae, with or without daily medium changes, in roller or stationary tubes. Inoculation was performed either directly on CAM fragments in Petri dishes or by dilution of the virus-containing material in the medium. Infectant titers obtained in CAM fragments were similar to those recorded in embryonated eggs at 48 hours post inoculation (p.i.) in the case of influenza virus A(H1N1) and at 72 hours p.i. in that of Sendai and influenza A(H3N2) viruses; at 96 hours p.i. all the three viruses had titers superior to those found in the egg. PMID- 6264663 TI - [Detection of rotavirus antigens and antibodies by immunoelectro-osmophoresis]. PMID- 6264664 TI - An immunological approach to the infectious mononucleosis syndrome. PMID- 6264665 TI - Genome distribution of adenovirus total and self-complementary nuclear RNA at early times. PMID- 6264666 TI - SV40 mutants with an altered small-t protein are tumorigenic in newborn hamsters. PMID- 6264667 TI - Esh avian sarcoma virus codes for a gag-linked transformation-specific protein with an associated protein kinase activity. PMID- 6264668 TI - Transformation parameters induced in chick cells by incubation in media of altered NaCl concentration. PMID- 6264669 TI - The metabolism of SV40 RNA is associated with the cytoskeletal framework. PMID- 6264670 TI - Host range deletion mutant of vaccinia virus defective in human cells. PMID- 6264671 TI - Structural and nonstructural proteins of strain Colburn cytomegalovirus. PMID- 6264672 TI - Regulation of protein synthesis in HEp-2 cells and their cytoplasmic extracts after poliovirus infection. PMID- 6264673 TI - Properties of mouse leukemia viruses. XVII. Factors required for successful treatment of spontaneous AKR leukemia by antibodies against gp71. PMID- 6264674 TI - DNA packaging in the lambdoid phages: identification of the products of phi 80 genes 1 and 2. PMID- 6264675 TI - DNA packaging in the lambdoid phages: the role of lambda genes Nu1 and A. PMID- 6264676 TI - Transcription of human hepatitis B virus core antigen gene sequences in an in vitro HeLa cellular extract. PMID- 6264677 TI - Protein A-coated erythrocyte binding to cell surface antigens: application to quantitate retrovirus infectivity in vitro. PMID- 6264678 TI - The structural relationships between 54,000-molecular-weight cellular tumor antigens detected in viral- and nonviral-transformed cells. PMID- 6264679 TI - Alteration of the 5' terminal caps of the mRNAs of vesicular stomatitis virus by cycloleucine in vivo. PMID- 6264680 TI - Recombination in adenovirus: crossover sites in intertypic recombinants are located in regions of homology. PMID- 6264681 TI - Identification of point mutations in the genome of the poliovirus Sabin vaccine LSc 2ab, and catalogue of RNase T1- and RNase A-resistant oligonucleotides of poliovirus type 1 (Mahoney) RNA. PMID- 6264682 TI - Ultraviolet inactivation of Epstein--Barr virus-induced nuclear antigen (EBNA), DNA and IgM synthesis in human B lymphocytes. PMID- 6264683 TI - Immunoprecipitation of virus-specific immediate-early and early polypeptides from cells lytically infected with human cytomegalovirus strain AD 169. PMID- 6264684 TI - Unintegrated and integrated proviruses of two strains of baboon endogenous viruses: comparative restriction endonuclease analysis. PMID- 6264685 TI - Baboon endogenous virus genomes in four species of baboons and five other genera of Old World monkeys: evidence for infection postspeciation. PMID- 6264687 TI - Cell-free translation of early and late mRNAs selected by hybridization to cloned DNA fragments derived from the left 14 million to 72 million daltons of the vaccinia virus genome. PMID- 6264686 TI - Inhibition of the neuraminidase of paramyxoviruses by halide ions: a possible means of modulating the two activities of the HN protein. PMID- 6264688 TI - Biochemical characterization of vesicular stomatitis virus-infected Aedes albopictus cells deprived of methionine. PMID- 6264689 TI - Herpes simplex virus thymidine kinase expression in trigeminal ganglion infection: correlation of enzyme activity with ganglion virus titer and evidence of in vivo complementation. PMID- 6264690 TI - Immediate-early proteins of human cytomegalovirus strains AD 169, Davis, and Towne differ in electrophoretic mobility. PMID- 6264691 TI - Preferential expression of endogenous type C viral antigen in Rhesus placenta during ontogenesis. PMID- 6264692 TI - Segregation of chicken endogenous viral loci ev 7 and ev 12 with the expression of infectious subgroup E avian leukosis viruses. PMID- 6264693 TI - Differential precipitation of foot and mouth disease virus proteins made in vivo and in vitro by hyperimmune and virus particle guinea pig antisera. PMID- 6264694 TI - [Results of surgical in undifferentiated small cell cancer of the lung]. AB - The results of surgical treatment of 36 patients suffering from undifferentiated small-cell carcinoma of lung are discussed. During the first two years, 28 patients (78%) died as a result of tumor progression, while 8 patients (22%) survived for 3--20 years after operation. Retrospective study established that the majority of the patients had a small -- size peripheral tumor without metastases in regional lymph nodes. Histological examination revealed a considerable development of stroma having a structure of mature fibrous tissue, few mitoses and no necroses. The findings show that in some cases of early stages of undifferentiated small-cell carcinoma of the lung, surgery may assure a long survival of tumor patients. PMID- 6264695 TI - [Hypothalamic endocrinopathy in histiocytosis X (author's transl)]. AB - Histiocytosis X in a 2-year-old boy with mainly skull manifestations was treated with radiotherapy and cytostatic drugs. Diabetes insipidus and growth retardation followed. Secretory capacity of GH was variable, periods of normal and insufficient secretion alternating during the 15-year observation period; there was a satisfactory response to GH therapy for one year. Thyrotropin and ACTH deficiency were diagnosed 3 1/2, and again 9 years after termination of histiocytosis therapy. Since there was no relapse of histiocytosis, this hypothalamic endocrinopathy is interpreted as being a late sequela of radiotherapy. PMID- 6264696 TI - The Chinese epidemiological approach of nasopharyngeal carcinoma research and control. AB - Nasopharyngeal carcinoma (NPC), the major cancer killer in Cantonese Chinese, represents one of the three cancer research priorities in China. Apart from some fundamental research projects on the Epstein-Barr virus (EBV), their main efforts are epidemiologically and clinically oriented. Major surveys in GuangDong and GuangXi provinces showed that high EBV/IgA/VCA serum levels can detect NPC at an early stage of the disease. Characterization of "precancerous lesions" in the nasopharynx and among the EBV/IgA positive individuals is in progress in the Zangwu county of the GuangXi Autonomous Region. Preventive anti-viral intervention in these individuals is being discussed. Search for genetic and environmental chemical carcinogens is also carried out. This Chinese epidemiological approach complements well the fundamental Western studies on EBV and NPC. PMID- 6264698 TI - Acid and alkaline phosphomonoesterases in Egyptian snake venoms. AB - Non-specific acid and alkaline phosphomonoesterases could be demonstrated in two viperids (Cerastes cerastes and Cerastes vipers) and two elapids (Naja haje and Naja nigricollis). The latter could be a natural source for the production of these enzymes. The activities of both enzymes in elapids were greater than in viperids. N. nigricollis was the only to show acid phosphatase activity exceeding its alkaline one. The optimum pH values recorded for acid phosphatase was 4.0 and 4.9 and for alkaline phosphatase 9.0 and 10.0 in viperids and elapids, respectively. Optimum substrate concentration for both enzymes in viperids was 0.01 M, while for acid phosphatase in N. haje and N. nigricollis it was 0.125 and 0.150 M; and for their alkaline phosphatases the values were 0.150 and 0.125 M, respectively. Mg++ behaved as an activator for both enzymes in all venoms investigated, while Zn++ showed either no or slight activating effect. Fluoride ions as well as EDTA showed certain inhibitory action. Both enzymes in the crude venoms were heat-labile. PMID- 6264699 TI - Preferential phosphorylation of high mobility group protein 17 in vitro by a nuclear protein kinase. AB - The ability of the high group proteins (HMG-1, 2, 14 and 17) to serve as substrate for protein kinases was investigated by incubating them with a cytoplasmic and nuclear kinase. In both cases phosphate was incorporated into all four HMG proteins. The amount of phosphate incorporated and the specificity for the four proteins was quite different for the two kinases. Whereas the cytoplasmic kinase phosphorylated the HMG-1 and 2 to a higher degree than HMG-14 and 17, the nuclear kinase exhibited a high specificity for the HMG-17, leaving the other three proteins with only a small amount. The high preference of a nuclear kinase for HMG-17 may be indicative of a specific phosphorylation occurring also in vivo. PMID- 6264697 TI - Beneficial effects of human viruses. AB - In keeping with the theme of this Yale-China symposium, we discuss some unexpected dividends which have been derived from the basic study of five viruses to which man has been exposed. Inquiring into the behavior of these viruses for their own sake has not only produced an increase in basic understanding of biologic processes, but has provided concepts and techniques which will broaden our knowledge of the etiology, pathogenesis, and treatment of human diseases which are unrelated to viruses. PMID- 6264700 TI - Purification of murine and feline type-C virus envelope polypeptides as micellar protein complexes. AB - A technique originally described for the isolation of Friend leukaemia virus envelope polypeptides [1] yields equivalent structures from Moloney leukaemia. AKR and BALB/c xenotropic virus as well as feline leukaemia virus. The envelope polypeptides are obtained as micellar protein complexes, named rosettes. Rosettes of the five mammalian type-C viruses examined are indistinguishable by electron microscopy. Separation of these aggregates in polyacrylamide gel electrophoresis under nonreducing conditions reveals a glycoprotein of about 85000 d as their major component. Tryptic peptide analyses identify the viral origin of these polypeptides and emphasize strain specific differences in their primary structure. PMID- 6264701 TI - Cytopathogenicity of Entamoeba histolytica: trophozoite homogenates modulate DNA synthesis in a mammalian cell line. AB - We examined the effect of total trophozoite homogenates from four axenized strains of Entamoeba histolytica (HK9, HM1, HM2, and HM3) on the DNA synthesis of subconfluent cultures of Chinese hamster ovary (CHO) cells incubated at low (0.1%) serum concentration. HM1, HM2, and HM3 extracts increased [3H]thymidine incorporation to acid-insoluble material in CHO cells up to a maximum of 2.5, 1.5, and 1.5 times respectively, at doses of amebal protein ranging from 16 to 125 micron/ml. HM1 and HM2 extracts at doses higher than those causing maximal stimulation, and HM3 and HK9 extracts above 250 micron protein per ml, progressively inhibited [3H]thymidine incorporation by CHO cells at a strain specific rate. The extracts with both the most potent stimulatory and inhibitory effects were those from HM1 and HM2, also the most virulent strains. This strain specific ability of amebal products to modulate cell DNA synthesis may play a significant role in amebal virulence. PMID- 6264703 TI - [Contraction-relaxation cycle in the heart]. PMID- 6264702 TI - [Physiological aspects of phosphoinositide metabolism]. PMID- 6264704 TI - [Vascular tumors, II. Glomus tumor (glomangioma)]. PMID- 6264705 TI - [Purification and identification of Eco CK restriction endonuclease]. PMID- 6264706 TI - [Current methods of isolating specific endonucleases]. PMID- 6264707 TI - [Construction and properties of a 2-replicon hybrid plasmid bearing the galactose operon of E. coli]. PMID- 6264708 TI - [EcoR1 restriction in vivo: possible utilization in genetic engineering]. PMID- 6264709 TI - [Physical mapping of simian adenoviruses]. PMID- 6264710 TI - [Controlled fragmentation of chromatin DNA by certain endonucleases, their isolation and properties]. PMID- 6264711 TI - [Complementarily directed DNA fragmentation and aspects of its application to genetic engineering]. PMID- 6264712 TI - [Formation and preservation of conditioned taste aversion in dogs]. PMID- 6264713 TI - [Giant polyfunctional neuron of the edible snail]. AB - The structure of the receptive field of LPa3 neurone and its connection with the periphery were studied on semi-intact preparations of the snail Helix pomatia. It was found that: 1) The mechano-sensitive receptive field (excitatory) of the LPa3 neurone occupies nearly the whole surface of the snail's skin and internal organs. But latencies of LPa3 reactions to mechanical stimulation, the whole field may be divided into four zones: 50 to 60 ms, 100 ms, 130 to 140 ms and 200 to 250 ms. 2) Blockade of synaptic transmission with magnesium or cobalt has shown that relaying of the signal from the mantle receptors to the LPa3 neurone takes place in the peripheral nervous system. 3) Cobalt ionophoresis showed that the LPa3 neurone gives off processes to the right and left pallial nerves, the anal nerve and, occasionally, to the cutaneous nerve. During simultaneous intracellular recording from the LPa3 neurone and extracellular from the above nerves, action potentials are in every case recorded at first in the neurone body, and then, with a 20 to 30 ms delay, in the nerves. This means that the LPa3 neurone processes joining the nerves are axons. It is suggested that the sensory inputs and wide branching structures output of the LPa3 neurone axons make it an integrating polyfunctional system. PMID- 6264714 TI - [Adrenoleukodystrophy (author's transl)]. AB - A report on clinical course and morphological findings of a case of adrenoleukodystrophy in a 10-years-old boy is given. The brain showed the typical changes of a sudanophilic, inflammatory leukodystrophy in all lobes. Pathognomic intracytoplasmatic inclusions in the perivascular macrophages were found by electron microscopic examination. The adrenal glands showed a severe atrophy, but it was impossible to detect typical cytolpasmatic inclusions within the adrenocortical cells. By thin-layer chromatography an accumulation of cholesterol esters with very long chain fatty acids was found in the demyelinated areas. Findings diagnostic facilities and theories of pathogenesis are discussed. PMID- 6264716 TI - [Effect of certain factors on the variability of strains of pertussis microbes]. AB - The population of degraded cells having stable changes in some phenotypical properties were isolated after subculturing some laboratory Bordetella pertussis strains in Bordet-Gengou culture medium and casein-charcoal agar with blood, treated with mitomycin C and allowed to proliferate in the spleen of mice injected intravenously with microbial suspensions. The characteristics indicative of cell degradation were the growth of large yellowish-white colonies appearing in 24 hours, the destruction of the agglutinogenic complex and toxic substances causing the atrophy of the spleen in mice, the increased capacity for active proliferation in the spleen. Electron-microscopic study revealed that the variants obtained by subculturing in culture media had the damaged membrane with the formation of cell-wall invaginations having rounded membrane-like formations on their surface, disappearing after treatment with mitomycin C; the treatment of the initial strains with mitomycin C resulted in cytoplasmic damage with the coagulation of the nucleoid. PMID- 6264717 TI - [Isolation of enterotoxigenic strains of Cl. perfringens type A and a study of their enterotoxinogenesis]. PMID- 6264715 TI - [Methods of biologic testing of enterotoxins]. PMID- 6264718 TI - Suppression of human lymphocyte mitogen response by disrupted primate retroviruses of type C (baboon endogenous virus) and type D (PMFV). AB - Disrupted primate retroviruses of type C (baboon endogenous virus, BaEV) and type D (human cell line-derived isolate PMFV) considerably suppressed Concanavalin A - induced blastogenic response of human lymphocytes. Rauscher mouse leukemia virus (RLV) displayed a suppressive activity on murine splenic lymphocytes when tested under analogous conditions. The immunosuppressive activities were shown not to result from cytotoxicity or from virus-mitogen binding. PMID- 6264719 TI - High order packing of DNA as revealed by autodigestion of chromatin in small intestine cell nuclei. AB - Small intestine cell nuclei incubated in sucrose media released large fractions of DNA into the culture medium. This effect was partially or completely suppressed when incubation was carried out in the presence of a protease inhibitor, 10 to 30 mM NaHSO3. The DNA released in sucrose media containing NaHSO3 was precipitated as a DNA-protein complex by increasing the bivalent ion concentration to 10 mM Ca2+ or 20 mM Mg2+. Most of the released DNA was not precipitated by Ca2+ or Mg2+ when incubation was performed without NaHSO3. As determined by viscosity measurements the mean molecular weight of the DNA released in the absence of NaHSO3 was from 3.5-8.0 x 10(5) and increased to about 11 x 10(5) (corresponding to 8 nucleosomes) when the incubation mixture contained NaHSO3. End group analysis indicated that the DNA segments were terminated by 3' OH groups. It is suggested that fragmentation of DNA in chromatin was produced by a endogenous alkaline endonuclease activity which was present in the fraction of released DNA. The data support the view that the third-order repeat structure of chromatin consists of subunits containing 8 nucleosomes. PMID- 6264720 TI - [Carcinoid tumors, adenoid-cystic carcinomas and muco-epidermoid carcinomas of the tracheo-bronchial tree (author's transl)]. AB - A retrospective study of 25 cases with a so-called bronchial adenoma was made. Classification by this old-fashioned nomenclature included 76% carcinoid tumors, 20% adenoid-cystic carcinomas and 4% muco-epidermoid carcinomas of the trachea and bronchial tree. With regard to their malignant potential, the correlation between histological differentiation, invasiveness, metastatic spread and clinical evolution is discussed. An outline of the extent of therapy for each of the 3 types is given. PMID- 6264721 TI - The respiratory epithelium. VIII. Interpretation of cytologic criteria for human and hamster respiratory tract tumors. PMID- 6264722 TI - Glucose-clamp by artificial pancreas in the study and management of a patient with insulinoma. AB - Four euglycemic glucose-clamp studies by artificial pancreas (Biostator, Miles) have been performed during prolonged fast before and after pharmacological treatment in a patient with insulinoma. In the basal state a high glucose infusion rate (8.9 g/h) was unable to achieve the preselected blood glucose plateau of 80 mg/100 ml. The plasma insulin levels during this first glucose clamp were comprised between 18 and 50 microunits/ml. On the first day of diazoxide treatment (300 mg/die),. the glucose infusion rate decreased to 6.4 g/h, without variation in plasma insulin level, thus suggesting a diazoxide effect independent of the inhibition of insulin secretion. After 7 days of diazoxide treatment, a further reduction of glucose infusion (5.8 g/h), together with a lowering of plasma insulin levels (7-18 microunits/ml) was observed. Both in the basal state and during diazoxide treatment a circadian pattern of glucose requirement was noted, with lower glucose need and plasma insulin levels during the night. Surgery was undertaken with glucose-clamp by artificial pancreas; blood glucose level being higher than the preselected value of 80 mg/100 ml, simple monitoring of glycemia was performed. The excision of a single adenoma was followed by a substantial rise in blood glucose 20 min later. An additional glucose-clamp, performed 3 months after surgery showed a dramatic fall of the glucose infusion rate (2.9 g/h) needed to achieve the preselected blood glucose plateau, confirming the completeness of the intervention. This experience shows that glucose-clamp by artificial pancreas may be of great value in the study as well as in the pharmacological and surgical treatment of patients with insulinoma. PMID- 6264723 TI - [Follow-up of renal transplant patients (author's transl)]. AB - Renal transplant patients need careful follow-up, after discharge from the hospital. The complications observed after the third month in 117 patients are reported. Suggestion for a efficient follow-up are elaborated. PMID- 6264724 TI - An adverse reaction with hydralazine: a case study. PMID- 6264726 TI - Histochemical studies on the lateral geniculate bodies and visual cortices after optic nerve ligation in the mouse. PMID- 6264725 TI - Effects of adrenergic neuron and ganglion blockers on hemodynamics and plasma catecholamine levels after corticosteroids during hemorrhagic shock in the dog. AB - The involvement of adrenergic mechanisms in the ability of massive doses of methylprednisolone to potentiate the vasodilatory effects of phenoxybenzamine during controlled hemorrhagic shock was investigated. Dogs were subjected to ligation of the adrenals and, with the exception of the controls, were pretreated with either hexamethonium or bretylium. Despite careful surgery, the adrenal ligation, per se, failed to alter the concentration of plasma catecholamines. Hexamethonium and bretylium, on the other hand, both decreased the levels of plasma catecholamines: noradrenaline to a greater extent than adrenaline. Methylprednisolone was almost ineffective after ganglionic or adrenergic neuron blockade. Furthermore, the degree of vasodilation after methylprednisolone and phenoxybenzamine seemed to correlate better with plasma noradrenaline than with adrenaline. These findings indicate that the ability of methylprednisolone to induce vasodilation in the presence of adrenergic alpha-receptor blockade in hypovolemic shock in the dog relies on an intact release of noradrenaline from postganglionic adrenergic nerve terminals. PMID- 6264727 TI - Multiple system atrophy with neuronal intranuclear hyaline inclusions. Report of a new case with light and electron microscopic studies. AB - An 18-year-old girl died following a slowly progressive neurodegenerative disease of nine years duration. At 9 years of age, she developed intellectual deterioration associated with speech difficulty, pseudobulbar palsy and ataxia. The progression included spastic quadriplegia, anarthria, severe dysphagia, ophthalmoplegia, and pes cavus. There was no family history. The brain was uniformly small and the substantia nigra was not pigmented. Neuronal loss and gliosis involving globus pallidus, subthalamic nucleus, thalamic nuclei, brain stem, cerebellum, and spinal cord gave the picture of multisystem atrophy. Intranuclear hyaline inclusions were observed in numerous neurons of the central and peripheral nervous system. These were auto-fluorescent and were made up of intermingled straight filaments (8-9 nm in diameter). Only two previously reported cases showing these same inclusions are known. They are reviewed, compared, and discussed in relation to primary neuronal degenerations. PMID- 6264729 TI - [Cardiovascular and metabolic effects during longtime treatment with beta 2 stimulants (author's transl)]. AB - To study the influence of beta 2-stimulants on pregnant woman and fetus from cardiovascular and metabolic viewpoint, tests were conducted on pregnant rats and human clinical cases of threatened premature labor. 1) When terbutaline 800 micrograms was administered to groups of pregnant rats for 4 days and 8 days, body weight, and weight of liver, placenta and heart of both mother and fetus indicated the trend of decrease when compared to the control, but the difference was not statistically significant. 2) Concentration of c-AMP in the fetal serum was found to be less than the control (P less than 0.001) under the above conditions and consequently c-AMP/c-GMP indicated decrease. Concentrations of c AMP and c-GMP in the maternal, fetal cardiac tissue were in a decreasing tendency in the terbutaline group. In the patholo-histological studies, terbutaline induced myocardial necrosis was not observed. 3) In the past five years, of the terbutaline treated cases, specifically 15 cases of large dose and long period of administration were analyzed and the prognosis of their children were followed up. The doses were 20.6 mg (iv, im), and 1276 mg (po), arrest less than 37W was noted in four cases, but onset of SFD was not observed. During the administration term, no abnormality of mothers was noted before and after delivery, and unusual phenomenon was not recognized in the prognosis traced on newborns. PMID- 6264728 TI - Double tumors of anterior and posterior pituitary gland. AB - Double tumors were found in the anterior and posterior lobes of pituitary gland at autopsy in a patient who presented with progressive deterioration of mental status. The chromophobe adenoma of anterior lobe consisted of a mixture of non immunoreactive hormone containing cells and a few prolactin (PRL) and growth hormone (GH) cells in the mid portion whereas the periphery of the tumor contained immunoreactive cells for PRL, GH, thyroid-stimulating hormone (TSH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH). A microscopic focus of granular cell myoblastoma (GCM) was found in the posterior lobe. Differentiation of tumor cells into anterior pituitary cells and GCM is discussed. PMID- 6264730 TI - In vitro effect of some free estrogens or estrogen precursors on collagenase activity of uterine cervix. AB - In order to determine whether or not collagenase activity of the uterine cervix can be influenced by estrone (E1), estradiol (E2), estriol (E3), equilin, dehydroepiandrosterone sulfate (DHA-S) or dehydroepiandrosterone (DHA), the collagenase activity of extract of connective tissue of the uterine cervix treated with the drug was measured. A higher collagenase activity was obtained in pregnant cervix than that in nonpregnant ones. There was no difference in collagenase activity of the uterine cervix extract between control and drug (5 X 10(-5) M of E1, E2, E3, equilin, DHA-S or DHA) groups both in nonpregnant and pregnant conditions. After preincubation of tissue with 1 X 10(-5) M of the said drug at 37 degrees C for 60 min, the enzyme activity of the supernatant was also investigated. In nonpregnant conditions, no increase in the enzyme activity was observed. On the contrary, significant increase of the enzyme activity was obtained in pregnant uterine cervix preincubated with equilin, E3, DHA-S or DHA comparing to that of control group. However, this increase was not observed by E1 or E2. Elastase activity was also investigated on cervical connective tissue both in nonpregnant and pregnant conditions. No increase in elastase activity was observed in the pregnant cervix comparing to that of nonpregnant group. PMID- 6264731 TI - Granular cell tumor in the perineum. A review and case report. AB - Granular cell tumor is a lesion which clinically often resembles a fibroma. The tumor is, however, frequently ill-defined, and it may be mistaken for a malignant growth. The granular cell tumor is only rarely located to the perineum. A total of 55 cases have been reported. The diagnosis can be obtained by frozen section microscopy. Recurrence is prevented by excising the whole lesion. The development of malignancy is extremely rare. PMID- 6264732 TI - Pyrophosphate arthritis with local amyloid deposition. AB - Pyrophosphate and capsular chondromatosis were demonstrated histologically in 15 cases, 14 of which also exhibited local deposition of amyloid. A systematic examination of the joint capsule in 57 consecutive hip replacement operations for osteoarthritis revealed these changes in 6 of the cases (10.5 per cent). Microscopic examination which was done if intraarticular calcifications were grossly visible at operation, showed the same changes in 8 knees, 4 with osteoarthritis and 4 with meniscal disease. The changes were also seen in the menisci. Only one patient was suffering from chronic, polyarticular pyrophosphate arthritis. In the other cases neither change had been expected a priori, and the patients had no signs of systemic articular disease or amyloidosis. Most of them were elderly, but in good health. PMID- 6264733 TI - ACTH in normal children and children with pituitary and adrenal diseases. I. Measurement in plasma by radioimmunoassay--basal values. AB - Plasma ACTH was measured by radioimmunoassay including preliminary extraction onto adsorbent glass particles. Normal basal values for children 4-16 years of age were 11-82 microgram/ml, corresponding to values found in the literature. Normal values were found in girls with precocious puberty, children with McCune Albright and Beckwith-Wiedemann's syndrome. Values between 233 and 305 pg/ml were found in untreated children with congenital adrenal hyperplasia. In primary Addison's disease, very high levels (654-1 413 pg/ml) before cortisone therapy and their decline to nearly normal values during therapy are described. ACTH values in a case of pituitary Cushing's syndrome was just above the normal range (104-163 microgram/ml). PMID- 6264734 TI - Common variable immunodeficiency and purine nucleotidase and nucleoside phosphorylase deficiency. A case report. AB - The results of immunological and purine enzyme investigations in an adult male patient with common variable immunodeficiency, recurrent lymph node granuloma and splenomegaly are presented. Serum immunoglobulins were present in trace amounts only and a progressive loss of Ig-bearing peripheral lymphocytes were demonstrated. Furthermore, the mitogenic responses to PHA. ConA and PWM were markedly reduced and the ratio of T.m/T.g cells was decreased. Finally, a combined deficiency of lymphocyte purine 5-nucleoside phosphorylase was demonstrated in the patient. PMID- 6264735 TI - [Studies on potent analgesics. I. Synthesis and analgesic activity of derivatives of fentanyl (author's transl)]. PMID- 6264736 TI - Nervous regulation of abomasum motor activity in sheep. AB - Pharmacological studies of abomasum motor activity were carried out in 3 sheep with chronic fistulae in the rumen and the fundus and pyloric part of the abomasum. The contractions of these parts of the stomach were recorded by the balloon method. The obtained results showed that in the abomasum stimulation of alpha-adrenergic receptors raises the degree of motor activity while stimulation of beta-adrenergic receptors inhibits it. It has been shown also that the sympathetic system has a greater influence through the beta-adrenergic receptors on the motor activity of the pyloric part than on that of the fundus of the abomasum. The analysis of the records obtained after bilateral vagotomy demonstrated that the automatism of the pyloric part was greater than that of the fundus of the abomasum. PMID- 6264737 TI - Generation, in activation and level of blood kinins during tourniquet shock in rabbits. AB - Traumatic shock was induced by the tourniquet method compressing one thigh during 10 hours. Venous blood samples were taken from control animals, as well as twice in the nervous phase of shock - after application and before removal of the tourniquet, and in the humoral-toxic phase - 1, 3 and 5 hours after tourniquet removal, in groups of 10 animals. Determinations included blood kinin level, and plasma kininogen level, and the activity of kallikreins and kininases in the plasma. It was found that during tourniquet shock a significant change occurred in the whole blood kinin system. Proportionally to the severity of shock the level of free kinins and kallikrein activity increased 3-4, times and the level of kininogen and the activity of kininases decreased, especially 3 hours after tourniquet removal. PMID- 6264738 TI - Tocopherol in irradiation of temporary hypoxic tumours. AB - The influence of tocopherol on the effect of local irradiation under induced ischaemia by temporary tourniquet of two rat tumours transplanted intramuscularly into one hindleg was evaluated. An impaired retardation of growth rate occurred in tumours irradiated under ischaemia. This effect was eliminated by pretreatment of animals with tocopherol. In separate experiments the method of inducing ischaemia was investigated by MDO-electrode measurements of tumour tissue oxygen pressure. A significant tumour hypoxia was found under tourniquet of the tumour bearing leg of the animals. Pretreatment with tocopherol did not influence the tumour pO2. PMID- 6264739 TI - Computed tomography and lymphography of the retroperitoneal space in testicular tumors. A comparison. AB - The value of CT and lymphography of the retroperitoneum was compared in 31 patients with testicular tumors. In no patient with normal or equivocal lymphography was more information gained by CT. In abnormal cases, the presence of metastatic deposits was well detected at both examinations, but CT proved more useful in defining the exact extent of the tumor and facilitated the proper arrangement of the irradiation fields. A strategy in the sequence of investigation in testicular tumors is suggested, aiming to save CT time when CT information is not likely to be of significance for treatment planning. PMID- 6264740 TI - Histiocytosis X. VI. Angiotensin-converting enzyme activity. AB - The activity of the endothelial and macrophage derived angiotensin-converting enzyme in blood was within normal range in 12 patients with histiocytosis X, independent of extent and activity of the disease. In contrast to sarcoidosis and Gaucher's disease, histiocytosis X is not associated with elevated levels of angiotensin-converting enzyme. PMID- 6264741 TI - Skin wound-enhanced survival and myelocytopoiesis in mice after whole-body irradiation. AB - Skin wounding at 24 h before whole-body 60Co irradiation of mice raised the LD50/30 from 8.09 to 9.71 Gy resulting in a dose reduction factor of 1.2. Concentrations and quantities of myeloproliferative cells were examined at 3, 7, 10, and 14 days after 7 Gy, skin wounding 24 h before 7 Gy and in control non treated mice. Wounding before irradiation provoked an increase in marrow and splenic clonogenic cells that was earlier and greater than that noted for irradiated mice. Supranormal levels of splenic CFu-s and CFU-c were found in animals wounded before irradiation. M-CFC values were depressed throughout, although greater for combined injured animals than for irradiated mice. PMID- 6264742 TI - Kinetics of cell proliferation in a rapidly growing murine lymphosarcoma. AB - The growth kinetics of a murine lymphosarcoma were investigated the spleen and liver of mice by means of quantitative flow-cytofluorometric DNA measurements in individual cells in combination with 3H-thymidine incorporation into the DNA. The amount of DNA in the S-phase cells was calculated from the resulting DNA histograms. From the 3H-thymidine incorporation, related to the amount of S-phase DNA, the relative changes in the duration of the S-phase during the growth of the lymphosarcoma were estimated. A marked prolongation of the duration of the S phase was observed in the course of the growth of the lymphosarcoma. The disappearance of cells of higher ploidy normally found in the liver indicates the elimination of those normal cells in the course of the tumour growth. PMID- 6264743 TI - Effect of low dose irradiation on renal enlargement in children following nephrectomy for Wilms' tumor. AB - The effect of low dose irradiation on subsequent compensatory renal enlargement in a group of children operated upon with unilateral nephrectomy for Wilms' tumor is reported. Comparison groups were children whose remaining kidney received either no direct irradiation or irradiation to only the upper portion of the kidney. The rate of growth of the kidney in the irradiated group was slightly less but this was not statistically significant. Thus, radiation therapy in children with Wilms' tumor, so crucial to optimum survival, does not seem to cause significant renal toxicity. PMID- 6264744 TI - Radiation effects on cultured human lymphoid cells. Analysis using the growth extrapolation method. AB - The cloning efficiency of human normal and malignant lymphoid cells is usually low. Radiation effects in vitro on such cells can therefore not be analysed with conventional cloning. However, this problem can be circumscribed by using the growth extrapolation method. A panel of human leukemia-lymphoma cell-lines representing Epstein-Barr virus carrying lymphoblastoid cells of presumed nonneoplastic derivation and neoplastic T- and B-lymphocytes was used to test the efficiency of this method. The sensitivity to radiation could be determined for all these cell types. The growth extrapolation method gave generally the same result as conventional cloning demonstrated by comparison with one exceptional cell-line with capacity for cloning in agar. The sensitivity varied largely between the different cell types. A common feature was that none of the cell lines had a good capacity to accumulate sublethal radiation injury. PMID- 6264745 TI - Stable and comfortable afterloading cervix applicator. PMID- 6264746 TI - Treatment results in mammary carcinoma stages I-IV. AB - A retrospective review of 590 patients with breast carcinoma of all clinical stages is presented. The patients were treated mainly with radical mastectomy and postoperative irradiation. The overall 5- and 10-year survival rates were 59% and 45%, in stage I 83% and 76%, in stage II 64% and 47%, in stage III 29% and 14% and in stage IV 5% and 0%, respectively. Treatment methods, prognostic factors and differentiation grade of infiltrating ductogenic carcinoma have been analysed and the effect of these factors on the treatment results in different clinical stages is presented. PMID- 6264747 TI - Activity in cAMP phosphodiesterase in the early regeneration stage of planarian Dugesia lugubris (O. Schmidt). Ultracytochemical studies. PMID- 6264748 TI - Some aspects of labelling of proteins with colloidal gold. PMID- 6264749 TI - Pulmonary function in familial amyloidosis with polyneuropathy. AB - Pulmonary function tests were performed in 14 patients with familial amyloidosis with polyneuropathy. Low maximum expiratory and inspiratory pressures were found in all patients with advanced polyneuropathy, indicating that the neuropathy in this disease involves not only the extremities but also the respiratory muscles. The spirometric findings were consistent with a slight restrictive pattern in several patients, but in two of them the expiratory and inspiratory flows were also low. The intrapulmonary gas distribution was uniform in all. The diffusing capacity was reduced in patients who had had the disease for a long time, which suggests alveolo-capillary block caused by amyloid deposits. The arterial oxygen tension at rest was essentially normal in these patients. PMID- 6264750 TI - Intradural spinal metastases. AB - A medullary cone metastasis from an adenocarcinoma of esophagus, and a solitary lumbar spinal nerve root metastasis from a breast carcinoma, gave rise to two cases of cauda equina syndrome. Muscle strength in the lower limbs improved postoperatively, while the disturbances of bladder, bowel, and pelvic floor function remained unchanged in the 1st case. The second patient benefited from operation, and regained useful life despite vertebral osseous involvement. It is suggested that tumour cells reached the spinal cord and the subarachnoid space by haematogeneous spread and by way of perineural lymphatics respectively. PMID- 6264751 TI - [Paraneoplastic syndromes. Clinical and epidemiological study]. PMID- 6264752 TI - [Lesions of the nervous system in subjects with malignant neoplasms]. PMID- 6264753 TI - [A case of cerebellar syndrome in a patient with bronchial carcinoma]. PMID- 6264754 TI - [An unusual case of polyneuropathy in a subject with intracranial malignant melanoma]. PMID- 6264755 TI - [Familial amyloidosic polyneuropathy. Report of a case]. PMID- 6264757 TI - [Further data on complications of arteriovenous fistulas on the peripheral nerves in uremic patients treated with hemodialysis]. PMID- 6264756 TI - [Hereditary neuropathy with a tendency to compression paralysis. Electrophysiological, morphometric and ultrastructural study of 2 familial cases]. PMID- 6264759 TI - Recombinant DNA technology. PMID- 6264758 TI - [Neurological syndromes caused by hemoblastosis, including infectious and iatrogenic complications affecting the nervous system]. PMID- 6264761 TI - The use of health and social services in the management of stroke in the community: results from a controlled trial. AB - The use of hospital and community services during the follow-up of a controlled trial which evaluated the effectiveness of a stroke unit and medical units in the management of acute stroke in the elderly is described. Patients from the stroke unit received more health and social services compared with medical unit patients, particularly in the initial follow-up period. The use of services was not related to the functional outcome of patients at hospital discharge. No overall difference occurred between stroke unit and medical unit patients in hospital bed days used throughout the study. PMID- 6264760 TI - The coumermycins: developments in the late 1970s. PMID- 6264762 TI - Analysis of histamine actions by intra- and extracellular recording in hippocampal slices of the rat. AB - Extra- and intracellular recordings from CA1 pyramidal and dentate granule cells in hippocampal slices of the rat revealed a depressant effect of histamine which was usually accompanied by a hyperpolarization but no changes in conductance of the cell membrane. Synaptic potentials were unaffected. It is concluded that histamine has a post-synaptic action on ionic conductance in the dendrites, that allows a modulation of quick information transfer but no rapid synaptic transmission. PMID- 6264763 TI - The in vitro effect of ethanol on the histamine-sensitive adenylate cyclase system. AB - The effect of low concentrations (1-5%) of ethanol on the histamine-sensitive adenylate cyclase system was examined in guinea pig gastric mucosa and hippocampus homogenate. Ethanol in these concentrations caused a dose-dependent increase of the adenylate cyclase activity, and this effect was not inhibited by histamine antagonists. Phosphodiesterase activities were not affected by these concentrations of alcohol. Our in vitro findings agree well with the results of BUNCE and PARSONS [10]. PMID- 6264765 TI - Lymphocyte-macrophage-fibroblast co-operation in the inflammatory degradation of cartilage and connective tissue. AB - In tissue culture models of cartilage and connective tissue degradation, rabbit macrophages and fibroblasts are both independently capable to degrade cartilage proteoglycan due to the secretion of a metal-dependent neutral proteinase. However, only the fibroblasts significantly degrade the collagen due to a sufficient production of collagenase. Macrophages produce factor(s) that stimulate the secretion of collagenase and the degradation of collagen by fibroblasts. Soluble products released by stimulated lymphocytes increase that production and also markedly enhance the secretion of proteoglycan-degrading proteinase and of collagenase by the macrophages. These data support the view that macrophages and fibroblasts are among the main effector cells of cartilage degradation in rheumatoid arthritis and that they are regulated in this function by secretory products of nearby lymphocytes. PMID- 6264764 TI - Pulmonary function and histaminemia after polymyxin B inhalation. AB - Bronchial challenge with polymyxin B caused a significant bronchoconstriction in 85% of atopic asthmatics. In all atopic asthmatics in whom inhalation of polymyxin B elicited bronchoconstriction, a significant, although not always parallel to the grade of bronchoconstriction, increase in histaminemia was observed. If bronchoconstriction was not elicited, the increase in histaminemia did not occur. It constitutes evidence that the bronchoconstricting effect of polymyxin B is exclusively due to degranulation of mast cells and that histamine released in the bronchi can increase the concentration of histamine in the blood. PMID- 6264766 TI - Free radicals. Introductory remarks. PMID- 6264767 TI - Free radicals generation by the inflammatory cells. AB - One of the most impressive property of the leucocytes is that of changing the oxidative metabolism during various functions. When challenged with phagocytosable particles or with membrane perturbing agents such as chemotactic factors, detergents, lectins and other ligands, granulocytes and mononuclear phagocytes undergo a dramatic increase of oxygen consumption which is associated with the production of superoxide anion (O-2), of hydrogen peroxide (H2O2) and of hydroxyl radical (OH.). These events are referred to as "respiratory burst' . Most of the functions of the inflammatory cells (killing of micro-organisms, tissue damage, amplification of the inflammatory process) are linked to the production, to the fate and to the chemical reactivity of these highly reactive compounds. The authors examine the following aspects: (i) the mechanism responsible for the respiratory burst; (ii) the conditions present in the inflammatory site that induces the metabolic activation of leucocytes; (iii) the variability of the respiratory burst in different types of leucocytes; (iv) the fate, the interrelationships and the reactivity of the intermediate products of oxygen reduction; (v) the relationships between the inflammatory process and the production of free radicals by the inflammatory cells. PMID- 6264768 TI - The role of polymorphonuclear peroxidase-dependent oxidants in inflammation. PMID- 6264769 TI - Inflammation and superoxide production by macrophages. AB - Superoxide (.O-2) is demonstrated to participate at the prostaglandin phase swelling (2-4 h) of carrageenan paw edema. Superoxide production is inhibited in vitro by typical anti-inflammatory drugs, but these drugs did not scavenge superoxide which was produced by xanthine oxidase. Phosphate, pyrophosphate, ATP, ADP and sulfate were essential for superoxide production by macrophages. These anions can induce paw swelling and are reported to increase in rheumatic patients. A mixture of macrophages and lymphocytes from BCG sensitized guinea pigs was cultured for 2 days with SOD or D-mannitol. Nitroblue tetrazolium reduction (formazan formation) was inhibited by these agents, suggesting that the hydroxyl radical (.OH) is necessary for metabolic activation of macrophage. Lympholine-like factor of which production or release is enhanced by hydroxyl radical, activates macrophage. Production of oxygen radicals may increase rapidly by this chain cycle reaction. Possible relations of oxygen radicals to prostaglandin(s) biosyntheses, chemotaxis, lysosomal enzyme release protease participation, were discussed. Endogenous SOD, epinephrine, ceruloplasmin, blood plasma proteins, inflammatory fluid, may modulate the amount of superoxide by their superoxide scavenging capacities. PMID- 6264771 TI - Models of immune complex disease. AB - An inflammatory lesion commonly develops in certain organs (e.g. skin, brain, kidneys and joints) either when antigen in the tissue spaces reacts with precipitating antibody forming microprecipitates in and around small blood vessels or when antigen in excess in the blood stream reacting with potentially precipitating antibody forms immune complexes (ICs) that lodge in the blood vessels. Other factors known to be essential for the pathogenesis of such lesions include (a) the activation of complement components, (b) chemotaxis towards ICs of PMN leucocytes and macrophages, (c) phagocytosis of ICs and (d) the formation and release by the phagocytes of prostaglandins, lysosomal enzymes, toxic metabolites of oxygen and other mediators of inflammation and tissue damage. Knowledge of these pathogenetic mechanisms opens up possibilities for chemotherapeutic attenuation or abolition of the development of antibody dependent inflammatory lesions. The extent to which this goal has been achieved in the clinic with the aid of substances selected through the use of models of immune complex disease will be reviewed in this presentation. PMID- 6264770 TI - Role of hydroxyl radical in polymorphonuclear leukocyte-mediated bactericidal activity. AB - Among the antimicrobial systems of polymorphonuclear leukocytes (PMNs) are those that are oxygen-dependent. Recent interest has been directed at the hydroxyl radical(OH.), a highly reactive reduction product of oxygen, as a possible mediator of microbicidal activity. The role of OH. in PMN microbicidal activity is discussed in relation to the observations that (1) an enzymic OH. generating system consisting of xanthine oxidase plus acetaldehyde is bactericidal, (2) phagocytosing PMNs convert substrates like methional and 5,5-dimethyl pyrroline-1 oxide to products suggestive of OH.-mediated reactions and (3) PMN-mediated microbicidal activity is partially inhibited by scavengers of OH. PMID- 6264772 TI - [The superoxide reaction in human diabetic cataract (author's transl)]. PMID- 6264773 TI - Properties of ovine adenoviruses. PMID- 6264774 TI - Small cell lung cancer: radionuclide bone scans for assessment of tumor extent and response. AB - Radionuclide bone scans were performed before and during combination chemotherapy in 119 systematically staged patients with small cell carcinoma of the lung. Before therapy, 49 patients (41%) had positive scans. Scan positivity was significantly associated with the presence of metastatic tumor in the bone marrow, positive skeletal radiographs, and elevated serum alkaline phosphatase levels. Nonosseous distant metastases were significantly more likely to be detected as the number of areas of focal abnormalities on bone scan increased. The survival of patients with documented distant metastases in bone and nonosseous sites was significantly inferior to the survival of patients with limited disease, isolated osseous extensive disease, and extensive disease occurring only in nonbony sites. Of 36 patients with initially abnormal scans and tumor regression documented by other methods, scan findings improved in 24 (67%). In 26 (36%) of 72 scans in patients demonstrating disease progression in extraosseous sites, new areas of increased radionuclide uptake appeared. Improvement or worsening in follow-up scans was associated with nonbony tumor response or progression, respectively, 70% of the time. Serial bone scans provide reasonably accurate staging and prognostic information in patients with small cell lung cancer, although they are probably not sufficiently reliable to be used as the sole parameter in therapeutic decision-making. PMID- 6264775 TI - Selective arteriography of glomus tympanicum and jugulare tumors: techniques, normal and pathologic arterial anatomy. AB - Glomus tympanicum and jugulare tumors arise within the middle ear and jugular fossa, respectively, but often extend into the adjacent areas of the skull base and posterior fossa. Multiple branches of the external carotid, internal carotid, and vertebral arteries may contribute to the vascular supply of these lesions. The arteriograms of 15 patients with glomus tumors were correlated with the surgical findings to determine if selective arteriography could define precisely the involvement within the middle ear, jugular fossa, and mastoid. The arteriographic mapping correlated well with the surgical findings in nine of 13 cases that had surgery, but a few important limitations were found. Therefore, a new arteriographic projection, called a transcanalicular view, is proposed that separates the middle ear from the jugular fossa, allowing for better visualization and assessment of the tumor blush. PMID- 6264776 TI - Physiological significance of benzo(alpha)pyrene adsorbed to carbon blacks: elution studies, AHH determinations. AB - Desorption of benzo(alpha)pyrene from commercial carbon blacks by tissue fluids in vitro is compared to arylhydrocarbon hydroxylase induction in mice at three levels of carbon black exposure. Less than 0.005% of the adsorbed benzo(alpha)pyrene content determined by soxhlet extraction in toluene is eluted by human plasma, swine serum, swine lung homogenate and swine lung washings. Statistically significant differences in elution efficiency are observed by the various tissue fluids and carbon blacks. There is no detectable increase in AHH level in mouse lung or liver tissues even at the highest carbon black exposure and consumption rate of 1g/g bdywt/year. PMID- 6264777 TI - Antiarrhythmic and hemodynamic effects of calcium channel blocking agents during coronary arterial reperfusion. Comparative effects of verapamil and nifedipine. PMID- 6264778 TI - The hematogenous origin of osteoclasts: experimental evidence from osteopetrotic (microphthalmic) mice treated with spleen cells from beige mouse donors. AB - The excessive skeletal mass and reduced bone resorption characteristic of osteopetrosis in microphthalmic (mi) mice can be corrected by irradiation and transfer of spleen cells from a normal littermate. Osteoclasts in beige (bg) mice, a mutation without osteopetrosis, have giant lysosomal granules. These two facts were exploited to trace osteoclast lineage. Microphthalmic mice treated with whole-body irradiation and spleen cells from a beige donor resorbed the excessive skeletal mass and recovered from osteopetrosis. Furthermore, osteoclasts in treated mi mice had giant lysosomal granules and resembled those found in bg donors when examined by light and transmission electron microscopy. These data provide direct evidence for a hematogenous origin of osteoclasts in mammals. PMID- 6264779 TI - Epidural metastasis by Wilms' tumor. AB - Metastatic spread is common in Wilms' tumor, but spinal epidural involvement is rare. We studied two patients in whom spinal cord compression developed during treatment of Wilms' tumor. Both patients had back pain and new pulmonary metastases months after the primary diagnosis was established. One case had evidence of adjacent vertebral involvement, and successful therapy was begun while the patient had minimal neurological deficits. The second patient had back pain initially without neurological deficit or abnormality on plain spine films, followed in one month by a rapid neurological deterioration. Despite a slow and nearly complete recovery after treatment with laminectomy, radiotherapy, and chemotherapy, her condition relapsed one year later, with a compressive lesion at a higher level. Our experience stresses the importance of early recognition of treatment of this complication of Wilms' tumor. PMID- 6264780 TI - Wilms' tumor in a 13-year old girl with trisomy 18. PMID- 6264781 TI - Hepatitis B testing in the families and villages of five young eskimos with primary hepatocellular carcinoma. AB - A 15-year-old female Eskimo and a 22-year-old male Eskimo from a southwestern Alaskan village (population 540) were diagnosed as having primary hepatocellular carcinoma (PHC) in December, 1977. The fathers of both patients also died of PHC. Three additional cases of PHC affecting young Alaskan Eskimos had been diagnosed since 1972, all from neighboring villages. Four of the five young patients were positive for hepatitis B surface antigen (HBsAg), and the family members of three patients were all positive for HBsAg or antibody to this antigen (anti-HBs). The other two families had no members positive for HBsAg. The prevalence of HBsAg in the villages of these patients ranged from 0--5%, and the prevalence of anti-HBs ranged from 3--25%. This part of Alaska has a high rate of infection with hepatitis B virus and an increased incidence of PHC. However, other Alaskan villages of similar ethnic background have considerably higher rates of hepatitis B infection than the four villages described and to date they have no PHC. This suggests that genetic and/or environmental factors in addition to hepatitis B infection may have a role in the etiology of PHC in Alaska. PMID- 6264782 TI - Terminal deoxynucleotidyl transferase-positive acute myeloblastic leukemia. AB - Terminal deoxynucleotidyl transferase (TdT) is a biochemical marker for acute lymphoblastic leukemia (ALL). In studies of ALL at diagnosis, there are usually greater than 40% TdT-positive cells by indirect immunofluorescence, whereas acute myeloblastic leukemia (AML) shows less than 1% TdT-positive cells. Rare cases of TdT-positive AML have been reported. We present here three AML patients with TdT in 15%, 45%, and 90% of the leukemic blasts. The diagnosis of AML was established on the basis of morphology and cytochemistry, and the cases included one patient with Auer rods. Myeloperoxidase was present respectively in 20%, 90%, and 5% of the blasts. There was no Philadelphia chromosome present in the three cases. These results may indicate the simultaneous presence of lymphoid and myeloid populations, or the presence of a blast cell with both lymphoid and myeloid markers. PMID- 6264783 TI - Freeze-drying of hemoglobin solutions without adjuvant and in presence of glucose, tris, and beta-alanine: a study by electron spin resonance of the oxidized compounds produced. AB - Hemoglobin cannot be freeze-dried without the presence of protective compounds. Carbohydrates are a well-known example of such compounds, but we have shown that some amine buffer and amino acids are also very effective. The mechanism of action of all these molecules is unknown. We report here experimental data showing that the protective effect is not the result of a direct bond between iron and the protective compound added. PMID- 6264785 TI - Meningeal carcinomatosis in small cell carcinoma of the lung. AB - Cerebral and meningeal metastases are increasingly important complications in small cell anaplastic carcinoma of the lung. In a study at this institution, 60 evaluable patients received intensive chemotherapy without prophylactic cranial irradiation or other prophylactic measures. The complete plus partial remission rate was 78 percent with a median survival of 49+ weeks (range eight to 106+ weeks) for those with a complete response and 18+ weeks (range six to 67 weeks) for those with a partial response, all of which are comparable to other reported series. In 11 patients (18 percent) meningeal carcinomatosis has developed. Forty two percent of the patients with a relapse have exhibited meningeal carcinomatosis and in 27 percent of the patients with a relapse it was the only site of relapse. Cerebral metastases occurred in 27 percent of those who had a relapse, and in 12 percent this was the sole site of relapse. Simultaneous meningeal carcinomatosis and cerebral metastases occurred in 8 percent of the patients with a relapse. The median time to meningeal relapse was 27 weeks (range 12 to 60 weeks) compared with 25+ weeks (six to 106+ weeks) over-all, and the median survival was 28 weeks (range 14 to 82 weeks) compared with 25+ weeks (two to 106+ weeks) for the whole group with small cell carcinoma of the lung. Meningeal involvement in small cell carcinoma of the lung must now be considered a sanctuary site of equal importance to cerebral metastases. To prevent and treat this complication will necessitate evaluation of all available modalities, including cranial and spinal irradiation, intrathecal chemotherapy and systemic agents that readily cross the blood-brain barrier. PMID- 6264784 TI - Niemann-Pick disease type B: prenatal diagnosis and enzymatic and chemical studies on fetal brain and liver. AB - Patients with Niemann-Pick disease type A have a severe neurovisceral disease caused by a deficiency of lysosomal sphingomyelinase activity in all tissues examined. The patients with the type B form have signs and symptoms related to storage of sphingomyelin in the spleen, liver, and lungs, while neurologically they remain normal. They also have a severe deficiency of lysosomal sphingomyelinase activity in all tissues previously examined. Here the brain and liver of a fetus with Niemann-Pick disease type B are examined for enzymatic anc chemical changes. Despite careful analysis, no measurable lysosomal sphingomyelinase could be measured in either organ. Lipid changes were comparable to those observed in fetuses aborted with Niemann-Pick disease type A. The affected child in this family is now age 3 and remains neurologically normal but continues to show organ enlargement and lung infiltration of lipids. It appears that the lack of neurological involvement in type B patients cannot be due to an obvious presence of significant lysosomal sphingomyelinase activity in brain. PMID- 6264786 TI - Hematology problem. PMID- 6264787 TI - Multiple congenital anomalies, thymic dysplasia, severe congenital heart disease, and oligosyndactyly with a deletion of the short arm of chromosome 5. AB - A female infant was born at term with congenital anomalies and a deletion of the short arm of chromosome 5. The anomalies included thymic dysplasia and lymphocyte depleted nodes of the type seen in combined immune deficiency; atrial and ventricular septal defects, pulmonary valve atresia, and anomalous pulmonary bronchial communication through the lungs; and shortness of forearms with syndactyly of fingers. A review indicates that the association of cardiac lesions, thymic dysplasia, oligosyndactyly and deletion of chromosome 5p is unique. PMID- 6264788 TI - Cryptophthalmos syndrome with bilateral renal agenesis. AB - We conducted a postmortem study of an infant with the abortive form of the cryptophthalmos syndrome. He had syndactyly and anal atresia and also showed features of Potter's (renal nonfunction) syndrome, including bilateral renal agenesis, pulmonary hypoplasia, and the typical facies. Histopathologic examination of both globes disclosed that the superior eyelid folds were partially replaced by skin that fused with the superior third of each cornea; there were also anomalies of the superior canaliculi and scarring of the corneas. We found no specific abnormality of the intraocular contents. PMID- 6264789 TI - Hemorrhage in newborn lambs: effects on arterial blood pressure, ACTH, cortisol, and vasopressin. AB - Arterial blood pressure, central venous pressure, and plasma concentrations of ACTH, cortisol, and vasopressin (AVP) were monitored in chronically prepared, unanesthetized newborn and weanling lambs at rest and during and after hemorrhage of 15% of estimated blood volume at 1.5%/min. Differences in the endocrine and blood pressure responses to hypovolemia were noted in the two groups of animals. Hemorrhage did not change arterial mean pressure, reduced central venous pressure, and caused a delayed increase in the plasma concentrations of ACTH, cortisol, and AVP in the newborn lambs. In weanling lambs, hemorrhage reduced arterial mean pressure and central venous pressure and promptly increased plasma ACTH and cortisol levels while plasma AVP concentrations again showed a delayed increase. The data indicate that certain hormonal mechanisms for the defense of blood volume are present and operational within 3 days of birth and that age related differences in the responses to hemorrhage exist in the lamb. PMID- 6264790 TI - Porcine granulosa cells in suspension culture. II. Luteinization and hCG responsiveness. AB - Granulosa cells from small follicles were cultured as suspensions in spinner flasks for 10 days in the absence or presence of follicle-stimulating hormone (FSH). With or without FSH, the cultured cells ultrastructurally resembled luteinized cells to different degrees. FSH increased progesterone accumulation in the culture medium. Ovine prolactin potentiated the effect of FSH in terms of the quantity of progesterone produced and the duration of accumulation. FSH increased acute human chorionic gonadotropin (hCG)-responsive progesterone secretion in short-term incubations of cultured granulosa cells. Responsiveness of FSH cultured cells was maximal at day 4; that of control cultured cells was maximal at day 6. Adenylate cyclase activity of homogenates of cells cultured for 4, 6, or 8 days was measured. FSH induced in cultured cells an hCG sensitivity of the adenylate cyclase enzyme. These results indicate that FSH induced hCG-responsive progesterone secretion and hCG-responsive adenylate cyclase activity that correlate with ultrastructural signs of luteinization and with the previously reported FSH induction of hCG receptors. PMID- 6264791 TI - Ontogeny of endocrine (ACTH, vasopressin, cortisol) responses to hypotension in lamb fetuses. AB - We studied the ACTH, vasopressin (AVP), and cortisol responses to nitroprusside induced hypotension in 27 chronically cannulated lamb fetuses between 0.53 and 0.98 gestation. Age-related differences in the hormonal responses to hypotension were found. Hypotension was associated with peak AVP levels of 7.8 +/- 2.7 pg/ml (mean +/- SE) in animals less than 0.68 gestation and 63.5 +/- 20 pg/ml in animals 0.89-0.98 gestation (P less than 0.05). The peak ACTH response was 95 +/- 20 pg/ml in the youngest animals and 380 +/- 111 pg/ml in animals 0.83-0.88 gestation (P less than 0.05). These observations suggest that maturation of the systems (possibly neuroendocrine) subserving the hormonal responses occurs in utero. Fetal plasma cortisol levels did not increase in response to the increase in ACTH except in animals 0.89-0.98 gestation. At this time, the basal plasma cortisol levels were high (58.8 +/- 16.8 pg/ml) and the ACTH response to hypotension was attenuated. Taken together, these findings suggest functional negative feedback regulation of ACTH by cortisol in the late gestation fetus. PMID- 6264792 TI - Inhibition of renin secretion by intrarenal alpha-adrenoceptor blockade. AB - This study was designed to determine whether renal alpha-adrenoceptors can mediate tonic neural stimulation of renin secretion. The effect of alpha adrenoceptor blockade by phenoxybenzamine (POB) or prazosin on renin secretion rate (RSR) was studied in pentobarbital-anesthetized dogs in which renal perfusion pressure was held constant with an adjustable aortic clamp. POB alone (100 micrograms.kg-1.min-1 iv) did not change arterial plasma renin activity (PRA). However, when beta-adrenoceptors were blocked by intravenous propranolol, intravenous POB infusion (100 micrograms.kg-1.min-1) decreased PRA and RSR to 48 +/- 8 and 21 +/- 9% of previous levels within 30 min. This effect was abolished by acute bilateral renal denervation. Direct intrarenal POB infusion (10 or 3.3 micrograms.kg-1.min-1) decreased RSR, whereas intravenous POB (3.3 micrograms.kg 1.min-1) had no effect on either RSR or PRA in propranolol-pretreated dogs. Prazosin (1 microgram.kg-1.min-1 iv) also significantly decreased PRA. These data indicate that when beta-adrenoceptors are blocked by propranolol, tonic neural stimulation of renin secretion is mediated by renal alpha-adrenoceptors. PMID- 6264793 TI - Corticoliberin activity of rat neurohypophysis is distinct from vasopressin. AB - Electrical stimulation of the neural lobe of the pituitary resulted in an increase of corticosterone secretion in both normal and Brattleboro rats. Bioassaying the corticoliberin (CRF) activity of stalk-median eminence and neural lobe extracts obtained from normal and Brattleboro rats revealed that the endogenous vasopressin was not a prerequisite of ACTH-releasing potency. Arginine 8-vasopressin failed to potentiate the CRF activity of the different extracts. These data suggest that a nonvasopressin substance(s) with CRF activity can be released from the neurohypophysis of the rat, and it may contribute to activating the pituitary-adrenal axis under certain experimental conditions. PMID- 6264794 TI - Developmental changes in rabbit and dog adrenal function: a possible homologue of adrenarche in the dog. AB - Histologic, hormonal, and enzymatic studies were performed in the rabbit and dog to identify maturational changes similar to human adrenarche. Development of an adrenal reticular zone was observed in both the rabbit and dog, analogous to the change in the man. Plasma dehydroepiandrosterone (DHA) and androstenedione (delta 4-A) increased significantly in postpubertal compared to prepubertal male rabbits and dogs, but the increases were much smaller than those reported in man. Orchiectomy reduced plasma DHA and delta 4-A of adult rabbit and dog to near undetectable levels, suggesting a primarily testicular origin. The activities of adrenal microsomal 17-hydroxylase and 17,20-desmolase in the orchiectomized rabbit and dog were subsequently measured to explain this apparent low adrenal contribution to DHA and delta 4-A. Adrenal 17-hydroxylase activity in the rabbit ad 17,20-desmolase activity in both the rabbit and dog were significantly lower than in an adrenal androgen-secreting primate (cynomolgus macaque). Adrenal 17 hydroxylase activity in the dog, measured 1 wk after castration, doubled after sexual maturation (P less than 0.001). This change was paralleled by a significant rise in basal and ACTH-stimulated plasma 17-hydroxyprogesterone in the intact dog (P less than 0.05). Because adrenal 17-hydroxylase activity has been shown to increase during adrenarche in man, this change may be homologous to human adrenarche. PMID- 6264796 TI - Mineralocorticoid effects on Na-K-ATPase in individual nephron segments. AB - A fluorometric micromethod for the assay of Na-K-ATPase was used to determine Na K-ATPase activity in 11 segments of the rabbit nephron. The Na-K-ATPase activity was found to be highest (greater than 100 pmol.mm1-.min-1) in proximal convoluted tubules (S1), medullary thick ascending limbs, distal convoluted tubules, and connecting tubules. There was a good correlation (r = 0.94) between Na-K-ATPase activity in different segments and net Na transport previously measured by in vitro tubule perfusion. Treatment of rabbits with deoxycorticosterone (DOCA) for 8-11 days produced increases in Na-K-ATPase activity of 100 and 500% in connecting tubules and cortical collecting ducts, respectively, without significant change in other segments. Maintenance on a low sodium diet for 12-18 days was associated with a 200% increase in Na-K-ATPase activity in cortical collecting ducts only. We conclude that the Na-K-ATPase activity is stimulated by mineralocorticoids in the cortical collecting duct in association with the previously observed changes in sodium transport. PMID- 6264795 TI - Effect of vanadate on renal tubular function in rats. AB - Orthovanadate (VO4) has been shown to cause a marked natriuresis in rats. This has been ascribed to its inhibitory action on renal Na-K-ATPase activity. Because virtually all nephron segments possess Na-K-ATPase activity the administration of VO4 should alter renal tubular transport along the entire nephron. To examine this possibility, adult rats were anesthetized and infused with VO4 (10 mumol.kg body wt-1.h-1 i.v.). This dose had no effect on glomerular filtration rate, effective renal plasma flow, and blood pressure, whereas urine flow and sodium and water excretion rose markedly. Potassium excretion remained unaltered. VO4 depressed only maximal bicarbonate and glucose reabsorption without causing a glucose or bicarbonate "leak" at normal levels of blood glucose or bicarbonate. In acutely thyroparathyroidectomized rats VO4 produced a striking phosphaturia, not accompanied by an increase in nephrogenous cAMP excretion. Both free water clearance in Brattleboro rats and free water reabsorption in normal rats was significantly depressed by VO4. These data demonstrate that VO4 depresses tubular reabsorption in proximal and distal nephron segments. We conclude that VO4 exerts its effect on tubular function by inhibition of Na-K-ATPase activity. PMID- 6264797 TI - Vasopressin-elicited refractoriness of the response to vasopressin in toad urinary bladder. AB - Incubation of the urinary bladder of Bufo marinus with high concentrations of vasopressin produces refractoriness to subsequent stimulation of water permeability by low concentrations of vasopressin. Development of refractoriness is directly dependent on concentration of vasopressin and duration of incubation with the hormone. Refractoriness develops in the absence of transepithelial water flow, is evident following a 2-h recovery period of incubation in hormone-free Ringer solution, and is reversed after prolonged incubation in hormone-free Ringer solution. Development and reversal of refractoriness is not altered by actinomycin D or cycloheximide. The steps at which refractoriness develops have been identified partially. Under different conditions, refractoriness involves: 1) reduced vasopressin-sensitive adenylate cyclase activity, 2) reduced epithelial cell cAMP accumulation in response to vasopressin the absence of demonstrable change in vasopressin-sensitive adenylate cyclase activity, cAMP phosphodiesterase activity, or loss of cAMP into the Ringer solution, and 3) refractoriness of water permeability response to exogenous cAMP. PMID- 6264798 TI - Transcellular transport of calcium and inorganic phosphate in the small intestinal epithelium. AB - Transport mechanisms involved in the small intestinal handling of inorganic phosphate and calcium have been studied by different in vitro methods during the last few years. In concordance with studies on intact epithelial preparations, studies with brush-border and basal-lateral membrane vesicles isolated from the small intestinal epithelial cell revealed that transcellular calcium and inorganic phosphate fluxes are coupled to transcellular sodium flux, i.e., secondary active via coupling to the primary active sodium flux. A sodium-coupled mechanism in the brush-border membrane leads to cellular accumulation of inorganic phosphate. A sodium-coupled mechanism leads to extrusion of calcium from the cell into the serosal interstitium. A primary active transport mediated by the Ca-ATPase and located in the basal-lateral membrane also exists for calcium. Regulation of transcellular phosphate and calcium flux proceeds via altered influx rates at the luminal cell pole. PMID- 6264799 TI - Mucosal gastrin receptor. VI. Induction by corticosterone in newborn rats. AB - Serum and antral gastrin levels as well as specific binding of [125I]gastrin-17 to a 270-30,000 g oxyntic gland mucosa crude membrane preparation were measured in rats between 5 and 40 days of age. Rats were normally weaned at day 18, although weaning was prevented in some animals until day 25. The results of these studies confirmed our previous data showing that mucosal gastrin receptors and antral gastrin levels begin to increase at the time of normal weaning and reach adult levels within a few days. Although the shift from liquid to a solid diet enhances the response, it is not essential for it and does not trigger it. In addition, the current studies demonstrated that injection of corticosterone caused a premature increase in both gastrin receptor and antral gastrin levels. Once maturation had occurred, however, corticosterone had no further effect. Adrenalectomy delayed but did not prevent the maturational changes in gastrin receptors and antral gastrin levels. Normal serum gastrin concentrations were necessary for the number of gastrin receptors and the amount of antral gastrin to reach normal levels. PMID- 6264800 TI - Contractile dysfunction of atrial myocardium from endotoxin-shocked guinea pigs. AB - Atrial muscle isolated from guinea pigs subjected to Escherichia coli endotoxin shock was used to study the myocardial changes associated with this experimental disease state. Isometric contractile tension and its first derivative (dT/dt) consistently were depressed by about 45% in muscle from the shock group (P less than 0.001), but contraction time intervals of the shock tissues were not significantly altered. The inotropic deficit of shock was completely antagonized by high concentrations of Ca2+ (greater than 4.5 mM). However, the maximal positive inotropic response to increased frequency of stimulation (0.1-2.2 Hz) only partially antagonized shock-induced cardiac depression. Heart muscle from shocked animals exhibited increased sensitivity to the negative inotropic effects of Mn2+, low Ca2+, and gentamicin; recovery from the depressant actions of these agents was prolonged 3.6- to 4.8-fold in shock. However, the negative inotropic potency of slow Ca2+ channel blockers, D 600 and nifedipine, was unaffected by shock. Similarly, studies with an isoproterenol-activated slow Ca2+ channel technique demonstrated equivalent inotropic responses of shock and control heart muscle. Present data provide evidence for a disruption of myocardial Ca2+ metabolism associated with endotoxin-induced inotropic depression of the heart but suggest that slow Ca2+ channels of the sarcolemma remain functional in this disease state. PMID- 6264802 TI - Contractility of vascular smooth muscle: maximum ability to contract in response to a stimulus. AB - The reactivity of vascular smooth muscle observed under the usual steady-state conditions (termed the usual reactivity) is generally relatively labile to changes in the external environment (e.g., to changes in PO2 or [K]o). However, reactivity during brief exposure to ouabain is nearly always greater than the usual reactivity and is relatively stable. It is demonstrated that for any given stimulus (i.e., a given concentration of a particular agonist), this latter reactivity is always the maximum that can be produced under any given set of conditions. Accordingly, it is proposed that the usual reactivity may be expressed as the algebraic sum of two properties of vascular smooth muscle: contractility, relatively stable property, which is defined as the maximum ability to contract in response to a stimulus, and electrogenesis, a relatively labile property, which produces a sometimes dominating electrical influence that modulates reactivity by opposing contractility. It is further proposed that because of the fundamental importance of these two properties it is useful to categorize all changes in reactivity, depressing or enhancing, according to whether they involve changes in contractility or electrogenesis. PMID- 6264801 TI - Different sites of adenosine formation in the heart. AB - In an attempt to further define the site of myocardial adenosine formation, isolated guinea pig hearts were perfused with potent inhibitors of 5' nucleotidase [alpha, beta-methylene adenosine 5'-diphosphate (AOPCP)] and of nucleoside transport [4-nitrobenzyl thioinosine (NBMPR)]. AOPCP (50 microM) inhibited the activity of cardiac ecto-5'-nucleotidase by 85% but did not influence the release of adenosine, inosine, and hypoxanthine formed at an accelerated rate by the heart during hypoxic perfusion (30% O2). In contrast, NBMPR (5 microM) diminished the hypoxia-induced release of adenosine and its degradatives and greatly potentiated the increase of myocardial tissue levels of respective purine compounds. Studies carried out with 5'-deoxyadenosine, an adenosine derivative that is not metabolized, indicate NBMPR to inhibit both uptake and release of adenosine in the isolated heart and in human erythrocytes. Cell fractionation studies on guinea pig ventricular muscle revealed that 5' nucleotidase, though mainly associated with the membrane fraction, is also found in the cardiac cytosol (200,000-g supernatant), exhibiting a different substrate specificity. Furthermore, S-adenosylhomocysteine hydrolase as well as adenosine kinase and adenosine deaminase proved to be exclusively present in the cytosolic fraction. Our findings suggest that in the hypoxic heart a) ecto-5'-nucleotidase most likely is not involved in the formation of adenosine, b) release of adenosine from the heart requires adenosine to be transported across the sarcolemma membrane, and c) adenosine is predominantly formed intracellularly, a process involving cytosolic 5'-nucleotidase and/or S-adenosylhomocysteine hydrolase. PMID- 6264803 TI - Possible mechanisms of stimulus-induced vacuolation in serous cells of tracheal secretory glands. AB - Several factors affecting the stimulus-induced vacuolation in cat tracheal submucosal glands described in a companion paper [Am. J. Physiol. 241 (Cell Physiol. 10): C18-C24, 1981] were examined. Stimulation with predominantly alpha adrenergic, beta-adrenergic, and cholinergic agonists at various concentrations and in the presence of appropriate blockers showed that alpha-adrenergic or cholinergic stimulation is more effective in inducing vacuolation than beta adrenergic stimulation. In addition, Ca- or HCO3- deficient incubation medium or low incubation temperature either blocked or significantly decreased the vacuolation response. Stimulation in the presence of the Na-K-ATPase inhibitor ouabain prevented vacuolation. The known roles of these factors in fluid transport are consistent with the possibility that stimulus-induced vacuolation possibly arises in response to disturbances in cytoplasmic fluid, which are induced in the secretory cell when the fluid component of secretion is intensely stimulated. A model is presented that possibly relates the observed responses to intracellular event and suggests the possibility of ion pumps in the apical membrane. PMID- 6264804 TI - Physiological and biochemical effects of iron deficiency on rat skeletal muscle. AB - Young rats were made iron deficient by feeding them a low-iron diet for 8 wk. Iron deficiency resulted in a 50% decrease in cytochrome c and cytochrome oxidase and a 26% decrease in mitochondrial glycerol-3-phosphate dehydrogenase activity in skeletal muscle. Respiratory capacity of muscle homogenates was reduced 55%. After 8 days of iron treatment, respiratory capacity, cytochrome c, cytochrome oxidase, and glycerol-3-phosphate dehydrogenase had returned 50% toward normal. Maximum O2 uptake of contracting hindlimb muscles averaged 8.5 mumol O2.min-1.g-1 in control, 4.3 mumol O2.min-1.g-1 in iron-deficient, and 6.2 mumol O2.min-1.g-1 in the 8-day-iron-repleted rats. Muscle fatigue during 10 min of stimulation was greater in the iron-deficient group. Lactate concentration in red muscle was higher in iron-deficient than in control rats after stimulation. The muscle fatigue and lactate responses returned 50% toward normal during 8 days of iron treatment. We conclude that iron deficiency results in a decrease in skeletal muscle capacity for aerobic metabolism and, by this mechanism, increases susceptibility to fatigue. PMID- 6264805 TI - Effect of vitamin D sterols and dietary magnesium on calcium and phosphorous homeostasis. AB - Calcium (Ca) and phosphorus (P) metabolism were studied in vitamin D-deficient rats as vitamin D status and dietary magnesium (Mg) were varied. Rats given normal (0.03%) or high (0.2%) Mg diets received either vehicle, vitamin D3 (1,650 pmol/day), or 1,25-dihydroxyvitamin D3 (60 pmol/day) for 9 days. In vitamin D deficient rats, high dietary Mg lowered intestinal Ca absorption from 40 +/- 5 to 11 +/- 5%; P absorption decreased 50%. Treatment with 1,25-dihydroxyvitamin D3 prevented the Mg-induced fall in absorption; vitamin D3 did so only for the first 6 days. The total Ca and Mg (Ca + Mg) absorbed (mM/day) decreased from 0.85 +/- 0.050 mM/day to 0.14 +/- 0.10 with the high dietary Mg; 1,25-dihydroxyvitamin D3 treatment raised Ca + Mg absorption regardless of diet Mg; high dietary Mg raised serum Ca despite a decreased intestinal Ca absorption and urinary Ca; treatment with either sterol had no added calcemic effect. These results are consistent with two processes for intestinal Ca and P transport: one vitamin D-dependent and the other non-vitsamin D-dependent and inhibited by high dietary Mg. Also high dietary Mg increases serum Ca, perhaps by affecting bone resorption. PMID- 6264806 TI - Role of Ca2+ in response of adrenal glomerulosa cells to angiotensin II, ACTH, K+, and ouabain. AB - The effects of Na+-K+-ATPase inhibition by ouabain and blockage of Ca2+ influx into the cell by verapamil and lanthanum on the response of isolated rat adrenal glomerulosa cells to angiotensin II, ACTH, and K+ were studied. Ouabain significantly increased basal aldosterone output at a concentration of 10(-5) mol/liter, whereas at 10(-3) mol/liter basal secretion was unaffected. Steroidogenic response to angiotensin II was significantly potentiated at concentrations of ouabain of 10(-5) mol/liter, but responses to angiotensin II, ACTH, and K+ were inhibited by 10(-4) and 10(-3) mol/liter of ouabain. The Ca2+ antagonist verapamil (10(-6) to 10(-4) mol/liter) decreased basal aldosterone secretion as well as the response to angiotensin II, ACTH, and K+. The effects of ouabain (10(-5) mol/liter) on basal and stimulated steroidogenesis were abolished by verapamil (10(-4) mol/liter). Lanthanum decreased basal and angiotensin II, ACTH, and K+ induced aldosterone secretion. The effects of ouabain (10(-5) mol/liter) on basal and stimulated aldosterone biosynthesis were blocked by lanthanum. These results suggest that Ca2+ mediates the effects of angiotensin II, ACTH, K+ and Na+-K+-ATPase inhibition on aldosterone biosynthesis. Ca2+ may be the final common intracellular messenger of most aldosterone secretagogues. PMID- 6264807 TI - Differential effects of cyclic nucleotide analogues and GnRH on LH synthesis and release. AB - We compared the effects of gonadotropin-releasing hormone (GnRH) and cyclic nucleotides on biosynthesis and release of luteinizing hormone (LH) by rat anterior pituitary glands (APs). APs from ovariectomized rats were incubated in the presence of test compounds, [3H]glucosamine, and [14C]alanine. GnRH significantly (P less than 0.01) increased both incorporation of [3H]glucosamine into LH (glycosylation) and release of immunoreactive LH (IR-LH) and [3H]LH. None of the cyclic nucleotides alone at 5 mM significantly stimulated release of IR LH. Adenosine 3',5'-cyclic monophosphate (cAMP), N6,O2'-dibutyryl cAMP (DBcAMP), and 8-bromo-adenosine 3',5'-cyclic monophosphate (8-Br-cAMP) stimulated (P less than 0.01) glycosylation, whereas 8-Br-AMP, 8-bromoguanosine 5'-monophosphate (8 Br-GMP), cGMP, and 8-Br-cGMP had no detectable effect. Release of [3H]LH was increased by GnRH, 8-Br-cAMP, and DBcAMP, but not by other nucleotides. None of the cyclic nucleotides elevated [14C]LH, whereas GnRH elevated it (P less than 0.01) in the medium. Dose-response curves for glycosylation in response to 8-Br cAMP and GnRH were parallel. In contrast, dose-response curves for release of both [3H]LH and IR-LH were nonparallel. It appears that cAMP can mimic the action of GnRH on LH glycosylation, but may have little direct effect on LH release. PMID- 6264808 TI - Kinin-induced prostaglandin synthesis by renal papillary collecting tubule cells in culture. AB - Cells having morphological and histochemical properties of collecting tubules were isolated from rabbit renal papillae. Confluent monolayer cultures of these renal papillary collecting tubule (RPCT) cells formed hemicysts and adhered with morphological asymmetry to Millipore filters. Cultures of 1-day-old RPCT cells synthesized cAMP in response to arginine vasopressin (AVP) (half-maximal response to 10(-10) M), oxytocin, and parathyroid hormone (half-maximal responses at 5 X 10(-9) M) but not to adrenergic agents. After 10 days of growth (fourfold increase in cell number) RPCT cells retained the same pattern of histochemical and hormonal responses as 1-day-old cells. Hormones were tested for their influence on the release of immunoreactive prostaglandins (iPG) by RPCT cells; the major product under both basal and stimulated conditions was iPGE2. At very low concentrations (greater than or equal to 10(-10) M), bradykinin, lysyl bradykinin, and methionyl-lysyl-bradykinin caused four- to sixfold increases in the rate of iPGE2 formation within 3 min; smaller (less than twofold) increases were observed with relatively high concentrations of epinephrine (10(-5) M), norepinephrine (10(-5) M), and angiotensin II (10(-7) M), but only after longer incubations. Significantly, neither AVP (10(-7) M) nor [deamino]AVP (10(-7) M) caused prostaglandin release by RPCT cells. Our results indicate that kinins can act directly on the collecting tubule to elicit PGE2 formation; furthermore, this effect of kinins may be natriuretic, since PGE2 has been shown to inhibit Na+ resorption by the medullary collecting tubule and thick ascending limb. PMID- 6264809 TI - Intestinal absorption of calcium: role of dietary phosphate and vitamin D. AB - The intestinal absorption of calcium (Ca) has been shown to depend on vitamin D3, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], and dietary phosphorus (P) concentration. This study was designed to evaluate the role of dietary P independent of vitamin D3 or 1,25(OH)2D3. Vitamin D-deficient rats were studied during dietary P restriction and were compared with control groups raised on a normal-phosphorus diet (NP). Balance studies were sued. Net intestinal Ca absorption was significantly lower with dietary P restriction compared with the NP group. This malabsorption of Ca was corrected by the administration of either D3 for 1,25(OH)2D3, despite hypophosphatemia. Everted gut sacs showed a marked reduction in the uptake of 45Ca in the duodenum, jejunum, and ileum during dietary P restriction. We concluded that dietary P concentration plays a major role in intestinal Ca absorption in the vitamin D-deficient rats. These findings suggest an effect of the low-phosphate diet on the vitamin D-dependent, Ca-transport mechanism. PMID- 6264811 TI - Dissociation of adrenal corticosteroid production from ACTH in water-restricted female rats. AB - These experiments were undertaken to investigate the mechanism whereby a precipitous drop in plasma corticosterone concentration is brought about following drinking in rats on a restricted water schedule. No alteration in adrenocorticotrophic hormone (ACTH) output was found, nor was catabolism of corticosterone sufficient to account for the drop. It is concluded that corticosterone level is controlled under these conditions by a mechanism independent of ACTH concentration. PMID- 6264812 TI - Comparative properties of tobacco hornworm, Manduca sexta, carbonic anhydrases. AB - Comparative properties of midgut, fat body and integumentary carbonic anhydrases (CAs) were measured as functions of CA-catalyzed CO2 hydration or p nitrophenylacetate (pNPA) hydrolysis in feeding larvae and pharate pupae. Alkali metal cations fully reverse the halide anion inhibition of CA catalyzed CO2 hydration during the larval but not the pharate pupal stages in development. Concentrations of acetazolamide required to inhibit 50% of tissue-specific CA catalyzed CO2 hydration (I50) were approximately 10(-8) M. The activity profiles between pH 6.0 and 9.0 had well-defined optima around pH 8.0 with activity declining dramatically above the optima. When CA-catalyzed pNPA hydrolysis was measured between 4 and 37 degrees C, insect enzymes failed to exhibit positive Q10 values between 25 and 37 degrees C. The affinities of the hornworm CAs toward pNPA were determined with stage- and tissue-specific Km ranging from 0.42 to 8.0 X 10(-3) M. It is concluded that tissue and stage-specific CAs exist in M. sexta, whose properties appear to differ markedly with those previously reported for mammalian enzymes. PMID- 6264813 TI - Gingival granula cell tumors of the newborn (congenital "epulis"): a clinical and pathologic study of 21 patients. AB - The clinical and pathologic features of 24 gingival granular cell tumors in newborns are reviewed. These tumors occurred exclusively in females and were localized on the anterior alveolar ridge (maxilla: 14; mandible: 9); the gingiva overlying future canine and lateral incisor teeth was most frequently involved. Follow-up data for 15 patients (average duration 15 years) indicated a lack of tumor recurrence despite incomplete resection in 11 instances. Tumors resected early in the newborn period were larger (maximum diameter 2.0 cm) and showed confluent to nodular submucosal growth with relatively less collagen. Some showed features suggesting involution. The histology in most cases supported a mesenchymal origin rather than one from odontogenic epithelium. Immunohistochemical staining for selected oncofetal and other antigens was negative. Electron microscopy did not entirely resolve the controversy regarding histogenesis. PMID- 6264810 TI - Prostacyclin-thromboxane interactions in the platelet-perfused in vitro heart. AB - A preparation of an isolated platelet-perfused guinea pig heart is described, which was utilized to study prostacyclin-thromboxane interrelationships. Infusion of washed human platelets (4 X 10(8)/min) through the coronary vascular bed stimulated the vascular PGI2 production from 114 +/- 27 to 350 +/- 30 pg/ml (P less than 0.01) and was associated with a significant increase in platelet cAMP from 1.2 +/- 0.4 to 2.6 +/- 0.9 pmol/10(8) platelets (P less than 0.05). Administration of arachidonic acid (AA) (45 micrograms) to the system led to a further increase (eight- to ninefold) of PGI2 and yielded marked thromboxane formation (20-25 ng/ml). Treatment of the hearts with aspirin (1 mM) prevented the PGI2 formation and AA-induced increase in platelet cAMP. Treatment of platelets with aspirin prevented thromboxane formation but did not influence AA induced changes in platelet cAMP and vascular PGI2 production. Bioassay data of PGI2 and rabbit aortic contracting substance gave results comparable to radioimmunoassay of 6-keto-PGF1 alpha and thromboxane B2. AA always decreased the coronary vascular resistance whether thromboxanes were formed or not. PMID- 6264814 TI - Trophoblastic pseudotumor of the uterus: clinicopathologic report with immunohistochemical and ultrastructural studies. AB - The clinicopathologic feature of two cases of trophoblastic pseudotumor of the uterus are presented and compared with previously reported cases. In both cases, cancer was erroneously diagnosed. One patient, 27 years of age when first examined, presented metrorrhagia 10 months after a full-term delivery. The lesion was entirely removed by curettage and was no longer found in the hysterectomy specimen. The patient is alive and well more than 17 years after therapy. The other patient, 36 years of age at the initial examination, presented with metrorrhagia 23 months after a therapeutic abortion. The pseudotumor infiltrated the full thickness of the uterine wall. The patient is alive and well 3 years and 7 months after hysterectomy and radiation therapy. Histologically, the tumor consisted of large cells invading the myometrium in small clusters either as cords or as single cells. There were 2 mitoses/10 HPF of which some were atypical. Tumor cells containing chorionic gonadotropin (hCG) and a pregnancy specific protein (SP1) were demonstrated immunohistochemically (alpha 2-PAG) and placental lactogen (hPL) in one case. Ultrastructurally, trophoblastic pseudotumor closely resembled cytotrophoblastic cells of the basal plate of the placenta. PMID- 6264815 TI - Trophoblastic pseudotumor: a reappraisal. PMID- 6264816 TI - Sensitive and rapid analysis of T1-ribonuclease-resistant oligonucleotides in two dimensional fingerprinting gels of poliovirus type I genomic RNA. PMID- 6264817 TI - Purification of human serum angiotensin I-converting enzyme by affinity chromatography. PMID- 6264818 TI - A rapid and sensitive assay of ADP glucose pyrophosphorylase using luciferase. PMID- 6264819 TI - Molecular weight determination of glyoxalated RNA by sedimentation centrifugation. PMID- 6264820 TI - The presence of progressive motility sustaining factor (PMSF) in human epididymis. AB - Progressive Motility Sustaining Factor (PMSF) was isolated from human epididymides. PMSF could significantly improve progressive motility of oligozoospermic as well as asthenozoospermic semen. PMSF was found to increase cyclic AMP accumulation by the human spermatozoa indicating its possible mode of action. PMID- 6264821 TI - Transient lower extremity weakness in an obstetric patient unrelated to epidural anesthesia. PMID- 6264822 TI - A study on beta-adrenergic receptors in children with asthmatic bronchitis. AB - The function of beta-adrenergic receptors was assessed in 50 children with asthmatic bronchitis and 45 healthy controls by the hyperglycemic, eosinopenic and platelet aggregation responses to epinephrine. The results showed evidence of beta-adrenergic blockade in children with asthmatic bronchitis. It is suggested that this blockade may reflect a functional and/or a structural immaturity of the beta receptors in these children. PMID- 6264823 TI - The use of anterior mediastinotomy to assess intrathoracic lesions. AB - A ten-year experience (1970-1979) with 164 anterior mediastinotomies at a VA hospital to diagnose pulmonary or mediastinal lesions or to assess the resectability of carcinoma of the lung is reported. of 135 attempts to obtain diagnosis, 130 (96%) were successful. Of 19 patients who had a subsequent thoracotomy because the anterior mediastinotomy suggested that a curative resection was possible, 17 (90%) had successful resections. Two (1.7%) patients died-one of a paraneoplastic syndrome and one from progressive respiratory failure. Eleven complications in the 162 survivors included eight minor wound infections, an initially unrecognized pneumothorax, persistent bleeding from a lymph node biopsy site, and an air leak necessitating reoperation in another. Anterior mediastinotomy is a relatively safe procedure, even in patients with advanced carcinoma or lung disease. it has much less risks than a formal thoracotomy and provides much better exposure and diagnostic possibilities than a mediastinoscopy. PMID- 6264824 TI - Phase plane analysis of uniform and non-uniform propagation of activity in a model of squid giant axon. AB - Mathematical modeling of propagation in the squid giant axon using the Hodgkin Huxley partial differential equation for propagation in a cable-like cell allowed us to study the effect of reduction in maximal sodium conductance in a short segment of the "axon membrane". The phase plane (V,V) display of the action potentials calculated in segments ahead of the gNa+ depressed site exhibited peculiar inflections in their ascending portion which are absent in the control situation. These inflections (upward or downward) varied with the distance from the depressed segments. The voltage of the first inflection point of the phase trajectories was an exponential function of this distance. This voltage is in close agreement with threshold voltage at points within a distance of 1.4 mm from the depressed segments. The model reproduces, qualitatively, the experimental behaviour of the squid axon topically exposed to TTX. PMID- 6264826 TI - Chloroplast origins: inferences from protein and nucleic acid sequences. PMID- 6264825 TI - Effects of dichloromethylene diphosphonate on serum and urinary calcium in primary hyperparathyroidism. AB - Dichloromethylene diphosphonate (Cl2MDP), an inhibitor of osteoclast function, was evaluated for its ability to lower the serum and urinary calcium in 14 patients with primary hyperparathyroidism. The study was double-blind, placebo controlled, and cross-over in design. All patients received 12 weeks of Cl2MDP (1600 mg daily) and 12 weeks of placebo in a randomized sequence. The average serum calcium was lowered by Cl2MDP from 11.5 +/- 0.1 mg/dL to 10.8 +/- 0.2 mg/dL (p less than 0.001). In the 3-month follow-up after drug administration, the average serum calcium (11.0 +/- 0.2 mg/dL) remained significantly below pretreatment levels (p less than 0.01). The reduction in serum calcium was accompanied by a significant decline in the urinary hydroxyproline excretion from 37 +/- 3 to 28 +/- 2 mg/g creatinine (p less than 0.01) and by a 40% reduction in the average urinary calcium excretion from 185 +/- 29 to 113 +/- 23 mg/g creatinine (p less than 0.01). Administration of Cl2MDP was not associated with any significant changes in parathyroid hormone levels or in urinary cyclic adenosine monophosphate excretion. No side effects were observed. We conclude that Cl2MDP lowers the serum and urinary calcium in patients with primary hyperparathyroidism. PMID- 6264827 TI - The establishment of mitochondria: Paracoccus and Rhodopseudomonas. AB - Many aerobic bacteria (both facultative and obligate) possess a number of those biochemical features of mitochondria which are concerned with energy metabolism. However, only restricted number, notably Paracoccus denitrificans and Rhodopseudomonas spheroides, have the majority of these features. The theory of endosymbiosis proposes that a primitive eukaryote took up bacteria to yield mitochondria. The present-day Paracoccus then resembles the ancestral bacterium in many respects the primitive amoeba, Pelomyxa palustris, which lacks mitochondria but contains a permanent population of unique symbiotic bacteria, has many of the characteristics of a present-day transitional form. The evolution of mitochondria from endosymbiotic bacteria would involve their integration with the host cell both biochemically and structurally: a number of the intermediate steps are discussed. Attention is drawn to the existence in some ciliates of hydrogenosomes, which function as anaerobic mitochondria. PMID- 6264828 TI - Two data sets: alternative explanations and interpretations. PMID- 6264829 TI - Pneumosinus Dilatans, Klippel-Trenaunay-Weber syndrome, and progressive visual loss. AB - A patient with Klippel-Trenaunay-Weber (KTWS), pneumosinus dilatans, and familial Adie's syndrome who developed bilateral perioptic meningiomas is described. This case demonstrates the efficacy of fine-needle aspiration biopsy for tissue diagnosis of optic nerve tumors in blind eyes. PMID- 6264830 TI - [Histological, etio-pathological and clinical characteristics of epithelial carcinoma of the ovary: analysis of 115 cases]. PMID- 6264831 TI - [Indications for exofacial parotidectomy in treatment of mixed tumors (author's transl)]. AB - Systematic total parotidectomy is still recommended by some authors for treatment of mixed tumors of the parotid. This attitude is based on the notion of multifocal involvement. In fact, multifocal involvement seems exceptional Very wide exeresis of the tumor is sufficient for efficient treatment, but the anatomical constitution of the parotid makes topographical division difficult. An attempt for systematisation of exeresis following the topography of the tumor is suggested, mainly for cases where parotidectomy is sufficient. PMID- 6264832 TI - [Determination and differentiation of rubella and cytomegalovirus infections antibodies by enzyme-linked-immunosorbent assay (author's transl)]. PMID- 6264833 TI - A ten-year experience with glomus tumors. PMID- 6264834 TI - Surgical management of parotid gland tumors. PMID- 6264836 TI - Myoepithelial adenoma of the lip-an unusual case. PMID- 6264835 TI - Hypoplasia of the latissimus dorsi muscle complicating breast reconstruction in Poland's syndrome. AB - Poland's syndrome includes anomalies of the breast, thorax, and upper extremity. Unilateral hypoplasia of the breast and pectoral muscle are seen most frequently, and the resulting problem of breast reconstruction must be addressed. The latissimus dorsi myocutaneous flap is one of the most useful reconstructive tools in this situation. A case is presented of Poland's syndrome with hypoplasia of the latissimus dorsi muscle-an abnormality not generally associated with Poland's syndrome. The latissimus dorsi muscle should be carefully evaluated preoperatively in such patients, to make sure it is adequate for reconstructing the absent breast and pectoral muscle. PMID- 6264837 TI - Surgical treatment of bronchial carcinoma. AB - The surgical treatment of 2430 patients suffering from bronchial carcinoma between 1950 and 1978 is analysed and emphasis placed on conservative surgery. The histological pattern is described, with marked prevalence of the squamous cell carcinomas. The increased age in the general population means that many patients aged 70 years or over present for surgical treatment and respond well to lobectomy or segmental resection. The place of preoperative radiotherapy in the treatment of oat-cell carcinoma is considered and it is concluded that improved results are obtained by this combined treatment. The serious consequences of a postoperative bronchial fistula are noted and the lower incidence that may be obtained by bronchial stapling is mentioned. The significance of a positive mediastinal node is stressed in relation to a long-term result from surgery, and methods whereby these results could be improved in the future are discussed. PMID- 6264838 TI - Secondary hyperparathyroidism in chronic renal failure. AB - The metabolic bone disease associated with chronic renal failure has been described collectively by the terms "renal osteodystrophy" or "renal-glomerular osteodystrophy" and consists of osteomalacia, osteitis fibrosa, and osteosclerosis. The skeletal abnormalities may occur either alone or in combination with one another. An increased concentration of circulating immunoreactive-parathyroid hormone (i-PTH) is a recognized feature of patients with chronic renal failure, and the values are usually much higher than those found in patients with primary hyperparathyroidism associated with a parathyroid adenoma. It must, however, be recognized that the high circulatory concentrations of parathyroid hormone found in patients with chronic renal failure are of immunoassayable material which may or may not be of biological significance in respect of activity. A disturbance in the homeostatic control mechanism governing parathyroid hormone, the secretion rate, its metabolism, and target organ resistance to its action are of major importance in the pathogenesis of some aspects of the metabolic bone disease in patients with chronic renal failure. The pathogenesis of the secondary hyperparathyroidism of chronic renal failure, however, also involves disturbances in cholecalciferol metabolism, phosphate retention, and the uremic state per se. PMID- 6264839 TI - [Short-term regulation of the production of glucose by the liver (author's transl)]. PMID- 6264840 TI - Liquid chromatographic assay of ketoconazole. AB - A reverse-phase, high-pressure liquid chromatographic method for the rapid and quantitative determination of ketoconazole has been developed. Drug levels from 0.5 to 10 microgram/ml can be determined in either yeast nitrogen base medium or human serum by using an octadecylsilane column. A retention time of 4.9 +/- 0.1 min resulted when the drug was eluted from a column with 75% methanol-25% 0.02 M (pH 7.5) phosphate buffer at a flow rate of 2 ml/min. Optimum sensitivity was obtained at a wavelength of 231 nm. PMID- 6264841 TI - Suction skin blister, skin window, and skin chamber techniques to determine extravascular passage of cefotaxime in humans. AB - We report the results obtained in comparative study on the extravascular passage of cefotaxime, employing three different methods: suction skin blister, skin window, and skin chamber. Applying the skin blister method in two different ways, we also studied the influence that suction pressure and time lapse between blister formation and antibiotic injection had on the results obtained in order to standardize the method and establish repeatability of the results. Using the skin chamber method, we studied the influence that the different protein contents in the fluid used to fill the skin chamber had on extravascular concentrations. PMID- 6264842 TI - Susceptibility of anaerobic bacteria to nine antimicrobial agents and demonstration of decreased susceptibility of Clostridium perfringens to penicillin. AB - The activity of moxalactam, cefoxitin, cephalothin, cefamandole, chloramphenicol, clindamycin, metronidazole, and ticarcillin was determined against 344 isolates of anaerobic bacteria. The activity of penicillin G was determined as well for 234 isolates not of the Bacteroides fragilis group. Moxalactam was more active than cephalothin and cefamandole and slightly less active than cefoxitin. Metronidazole was the most active antimicrobial agent against the B. fragilis group, whereas chloramphenicol was most active overall. Clostridium species were the most resistant group of organisms tested. Relatively high concentrations of penicillin were required to inhibit the C. perfringens strains: 80% at 0.5 U/ml and 100% at 16 U/ml. Our study demonstrates the need for periodic anaerobe susceptibility testing in order to better guide empiric antibiotic therapy. PMID- 6264843 TI - Molecular nature of a streptomycin and sulfonamide resistance plasmid (pBP1) prevalent in clinical Escherichia coli strains and integration of an ampicillin resistance transposon (TnA). AB - A small, nonconjugative plasmid, designated pBP1, was originally found in different fecal Escherichia coli serotypes isolated from a healthy proband. Of a total number of 130 hospital strains of E. coli subsequently studied, 8.5% yielded plasmid of the pBP1 type. This R plasmid specifies resistance to streptomycin (Sm) and sulfonamides (Su) and has a mass of 4.0 megadaltons. Inactivation of streptomycin is due to the aminoglycoside phosphotransferase APH (3 "). A physical map was constructed by analysis with restriction endonucleases. Another small plasmid, pBP1-1, was isolated from one of the hospital strains and characterized as an enlarged pBP1 replicon containing an additional deoxyribonucleic acid sequence identified as a transposable element for ampicillin resistance (TnA). Plasmid pBP1-1 was cleaved by restriction enzymes for identification of the transposon sequence which codes for a TEM 1 beta lactamase. The sequence organizations in the Sm Su plasmids RSF1010 and pBP1 were shown to be identical for regions specifying streptomycin and sulfonamide resistance, but different for the region containing the origin of replication and genes for replicative functions. Thus, RSF1010, which has been considered as the prototype of Sm Su plasmids, and pBP1, which is at least as frequent in clinical isolates as RSF1010, do not have a single common ancestor. PMID- 6264844 TI - In vitro activity of N-formimidoyl thienamycin in comparison with cefotaxime, moxalactam, and ceftazidime. AB - The in vitro activity of N-formimidoyl thienamycin (N-f-thienamycin) was compared with the activities of other B-lactam antibiotics, using over 500 clinical bacterial isolates. N-f-Thienamycin inhibited 90% of the isolates of the common Enterobacteriaceae between 0.006 and 2 microgram/ml, regardless of their resistance to amoxicillin, ticarcillin, or cephalothin. It was, however, fourfold less active than moxalactam and ceftazidime and eightfold less active than cefotaxime. N-f-Thienamycin was nearly as active as ceftazidime against Pseudomonas aeruginosa (mean minimal inhibitory concentration, 3.0 microgram/ml) and eightfold more active than cefotaxime and moxalactam. In contrast to cefotaxime, moxalactam, and ceftazidime, N-f-thienamycin was highly active against enterococci (mean minimal inhibitory concentration, 1.3 microgram/ml) and staphylococci. The oxacillin-susceptible Staphylococcus aureus were inhibited between 0.03 and 0.12 microgram/ml, and the oxacillin-resistant S. aureus were inhibited between 0.12 and 2 microgram/ml. The high activity of N-f-thienamycin against both of the most important gram-positive and gram-negative organisms makes it a very promising new antibiotic. PMID- 6264845 TI - Comparative in vitro studies of Ro 13-9904, a new cephalosporin derivative. AB - The in vitro activity of Ro 13-9904, a new cephalosporin derivative, was compared with the activities of cephalothin, cefamandole, cefoxitin, cefotaxime, and moxalactam against 591 clinical isolates of gram-negative and gram-positive organisms. The spectra of activity and potency of Ro 13-9904 and cefotaxime were quite similar; they were the most active agents against Enterobacteriaceae, Streptococcus pyogenes, Haemophilus influenzae, Neisseria gonorrhoeae, and Neisseria meningitidis. Moxalactam was only slightly less active against these organisms. Ro 13-9904, cefotaxime, and moxalactam were approximately equal in activity against Pseudomonas aeruginosa; concentrations of 50 to 100 microgram/ml inhibited over 90% of the strains tested. Cefamandole and cephalothin were the most active drugs tested against staphylococci. Moxalactam demonstrated the highest intrinsic activity against Bacteroides fragilis; a concentration of 1.6 microgram/ml inhibited over 50% of the strains. All six of the antibiotics were essentially inactive against group D streptococci. The action of all of the antibiotics was bactericidal, with minimal bactericidal concentrations generally being no more than twofold greater than minimal inhibitory concentrations. The only exception to this was found when large inocula of Staphylococcus aureus were tested. Increased inoculum size generally sharply reduced the activity of Ro 13 9904, cefotaxime, and moxalactam against Enterobacteriaceae and P. aeruginosa. PMID- 6264846 TI - Antimicrobial activity of cefmenoxime (SCE-1365). AB - The in vitro activity of cefmenoxime (SCE-1365 or A-50912), a new semisynthetic cephalosporin antibiotic, was compared with those of cefazolin, cefoxitin, and cefamandole against a broad spectrum of 486 organisms and with that of cefotaxime against 114 organisms. Cefmenoxime and cefotaxime exhibited nearly equivalent activities against those organisms tested and were the most active of these cephalosporins against all aerobic and facultative organisms except Staphylococcus aureus. The minimum inhibitory concentration (MIC) of cefmenoxime required to inhibit at least 90% of strains tested (MIC(90)) ranged from 0.06 to 8 mug/ml for the Enterobacteriaceae. The MIC(90)s for gram-positive cocci were 0.015 and 128 mug/ml with good activity against the gram positive organisms. In addition, cefmenoxime activity was bactericidal and only slightly affected by differences in inoculum size. The combination of cefmenoxime and gentamicin was synergistic against 80% of the Enterobacteriaceae and 100% of P. aeruginosa strains tested. Development of resistance to cefmenoxime was slow or absent for organisms with low initial MICs but more rapid for those with higher initial MICs. Cefmenoxime exhibited good protective activity in mice infected with Escherichia coli, Enterobacter cloacae, Proteus mirabilis, Proteus vulgaris, or S. aureus but was less effective against P. aeruginosa. PMID- 6264847 TI - Filament formation of Fusobacterium nucleatum cells induced by mecillinam. AB - Subinhibitory concentrations of mecillinam transformed Fusobacterium nucleatum cells into a marked filament form, quite different from a spherical form demonstrated in Escherichia coli. PMID- 6264848 TI - In vitro and in vivo effects of dapsone on neutrophil and lymphocyte functions in normal individuals and patients with lepromatous leprosy. AB - The effects of dapsone on polymorphonuclear leukocyte functions and lymphocyte mitogen-induced transformation were assessed in vitro and in vivo in normal individuals and in newly diagnosed untreated patients with lepromatous leprosy. The effects of dapsone on the cell-free generation of superoxide by the xanthine: xanthine oxidase system and iodination of bovine serum albumin by horseradish peroxidase were also investigated. In normal individuals dapsone mediated stimulation of polymorphonuclear leukocyte migration in vitro and vivo. Dapsone had no effect on postphagocytic hexose monophosphate shunt activity in vivo. Similar effects were found in patients with lepromatous leprosy. Dapsone also decreased the inhibitory activity of serum from patients with lepromatous leprosy on normal polymorphonuclear leukocyte migration in vitro. Progressive loss of serum-mediated inhibition of migration was observed after ingestion of dapsone by the patients. Further experiments showed that stimulation of polymorphonuclear leukocyte motility was related to inhibition of lymphocyte transformation at high concentrations in vitro, but had slight stimulatory activity on phytohemagglutinin-induced transformation in controls and patients in vivo. PMID- 6264849 TI - Pharmacology of cefotaxime and its desacetyl metabolite in renal and hepatic disease. AB - The pharmacology of cefotaxime and the metabolite desacetyl cefotaxime was studied in 40 patients with various degrees of renal and hepatic failure who received 0.5 or 1 g of cefotaxime intravenously. Patients with severe renal impairment (creatinine clearance, 3 to 10 ml/min) had a cefotaxime serum half life of 2.6 h and desacetyl cefotaxime serum half-life of 10.0 h. The equivalent figures were 1.0 and 1.5 h, respectively, in subjects with normal renal function. The presence of an acute coexisting illness together with severe renal impairment was associated with a further prolongation of the serum half-lives. Hepatic dysfunction was accompanied by a reduction in desacetyl metabolite formation. A reduction of cefotaxime dosing to 0.5 g twice a day would appear prudent when the creatinine clearance is 5 ml/min or less to avoid accumulation of the parent compound and the metabolite. PMID- 6264850 TI - Mecillinam susceptibility of Escherichia coli K-12 mutants deficient in the adenosine 3',5'-monophosphate system. AB - The mecillinam resistance of Escherichia coli K-12 mutants deficient in the enzyme responsible for the synthesis of adenosine 3',5'-monophosphate, adenylate cyclase, has been investigated. The results suggest that resistance to this antibiotic may be a consequence of the slow growth rate of these mutants rather than an intrinsic property of their genetic lesion. PMID- 6264851 TI - Resistance to antibiotic synergism in Streptococcus faecalis: further studies with amikacin and with a new amikacin derivative, 4'-deoxy, 6'-N-methylamikacin. AB - Streptococcus faecalis strains may resist penicillin-aminoglycoside synergy by the production of plasmid-mediated aminoglycoside-modifying enzymes. One of these enzymes, aminoglycoside 3'-phosphotransferase, has been shown to have a broad range of substrate specificity, including amikacin. We have studied a derivative of amikacin, 4'-deoxy, 6'-N-methylamikacin (BB-K311), against 11 clinical blood isolates of S. faecalis. Minimal inhibitory concentrations of BB-K311 were quite similar to those of amikacin, ranging from 125 to 1,000 micrograms/ml. In assays for antibiotic synergy, penicillin and amikacin produced enhanced killing compared with the penicillin alone only against those three strains which lacked the phosphotransferase enzyme. The other eight enzyme-positive strains actually demonstrated significant antagonism between penicillin against all 11 strains, regardless of enzyme production. Analysis of substrate profiles with crude preparations of the aminoglycoside 3'-phosphotransferase enzyme confirmed that BB K311 was a very poor substrate for modification, as expected from the synergy studies. Use of other aminoglycoside analogs confirmed the 3'-OH site of modification. These findings suggest that removing the 4'-OH group in amikacin effectively blocks 3'-phosphorylation by S. faecalis enzyme. PMID- 6264852 TI - Outer membrane permeability barrier disruption by polymyxin in polymyxin susceptible and -resistant Salmonella typhimurium. AB - In contrast to their polymyxin-susceptible parent strains, polymyxin-resistant Salmonella typhimurium mutants (pmrA strains) did not lose their outer membrane permeability barrier to macromolecules such as lysozyme and periplasmic proteins upon polymyxin treatment. The sensitization of pmrA strains to deoxycholate induced lysis required 10-times-higher polymyxin concentrations than did the sensitization of the parent strains. These findings indicate that the pmrA mutation affects the outer membrane and decreases its susceptibility to polymyxin. By contrast, the pmrA mutants did not differ from their parents in the uptake of gentian violet after treatment with polymyxin, suggesting a degree of specificity in the pmrA effect in the outer membrane. PMID- 6264853 TI - Antiviral activity of 2-acetylpyridine thiosemicarbazones against herpes simplex virus. AB - 2-Acetylpyridine thiosemicarbazone derivatives inhibited the replication of herpes simplex virus types 1 and 2 to a greater extent than cellular deoxyribonucleic acid or protein synthesis. PMID- 6264854 TI - On the significance of enzymes which confer resistance to aminoglycosides. PMID- 6264856 TI - The concentration of cholecystokinin in the intestinal tract of germ-free and control mice. PMID- 6264855 TI - The effect of exogenous CCK-8 on the transit time and colonization resistance of decontaminated mice. PMID- 6264857 TI - Co-purification of type I alkaline phosphatase and type I phosphoprotein phosphatase from various animal tissues. PMID- 6264858 TI - Cyanide catalyzes the oxidation of alpha-hydroxyaldehydes and related compounds: monitored as the reduction of dioxygen, cytochrome c, and nitroblue tetrazolium. PMID- 6264859 TI - Nitrofuran enhancement of microsomal electron transport, superoxide anion production and lipid peroxidation. PMID- 6264860 TI - Potentiation of hormone-stumulated accumulation of cyclic AMP in cultured fibroblasts by trypsin. PMID- 6264861 TI - A possible histiocytoma in an Egyptian mummy. AB - This report concerns the finding of a possible histiocytoma in the skin of the heel of an Egyptian mummy. Only two other neoplasms have been diagnosed microscopically in ancient material-a squamous papilloma of the hand in an Egyptian mummy and possible malignant melanomas in several Peruvian mummies. No visceral tumors have ever been identified in mummies, and only a few possible neoplasms have been detected on gross examination of skeletal material. The satisfactory preservation of cutaneous histologic and pathologic features in mummies should encourage the performance of additional studies. PMID- 6264862 TI - Pathology quiz case 2. PMID- 6264863 TI - Rotavirus, adenovirus, and non-viral enteropathogens in diarrhoea. AB - The aetiology of rotavirus and adenovirus in acute gastroenteritis was studied in a prospective series that comprised 283 children admitted consecutively with diarrhoea during a 1-year period. Rotavirus was associated in 49% of the cases by solid-phase radioimmunoassay and electron microscopical examination of stool specimens, or by serology. Adenovirus was detected by radioimmunoassay in the stool specimens of 29 (11%) patients, including 8 cases of possible dual infection with rotavirus. Rotavirus infections showed a typical age distribution and seasonal clustering between January and June, whereas the adenovirus associated cases did not form a distinctive subgroup. Enteropathogenic bacteria were found in 10% of cases, and were nearly as common in association with rotavirus infection as not. Respiratory symptoms accompanied diarrhoea in 34% of the patients with rotavirus and in 25% of those with neither rotavirus nor adenovirus. Therefore we could not confirm the existence of a 'rotavirus syndrome', nor could we confirm an association of respiratory symptoms with rotavirus infection. Use of antibiotics before the onset of diarrhoea was more common among those with non-viral diarrhoea (23%) than in the rotavirus group (13%). Rotavirus infections appeared to be common among cases of 'antibiotic induced' diarrhoea. PMID- 6264864 TI - Immunopathology of psoriasis. PMID- 6264865 TI - The effect of oral estrogen therapy on serum FSH and LH levels in young women with hyper-gonadotrophic ovarian failure. AB - Fourteen women, 18--46 years old (median age: 28 years) with hypergonadotrophic ovarian failure were each treated daily for 21 days with 10 micrograms, 20 micrograms, 40 micrograms, and 60 micrograms ethinyl estradiol, 2,000 micrograms estriol, and 1,250 micrograms conjugated estrogens in six or more consecutive treatment cycles in a randomly assigned sequences. Before treatment and at the beginning of the 3rd week of each of the mentioned estrogen regimens, basal serum FSH and LH levels were measured. During the last 5 days of each treatment cycle, 10 mg of oral norethisterone acetate were given in addition to the estrogen, and after a treatment-free interval of 7 days the next estrogen regimen was begun according to the random list. FSH values were inversely related to the various dosages of ethinyl estradiol; the upper normal range with the exception of the periovulatory phase was reached with 40--60 micrograms ethinyl estradiol. FSH levels during treatment with 1250 micrograms of conjugated estrogens were similar to those found during treatment with 20 micrograms ethinyl estradiol. When 2,000 micrograms of estriol were given daily, FSH levels rose of pretreatment values. LH behaved similarly except that during treatment with 2,000 micrograms of estriol and 10 micrograms of ethinyl estradiol values above pretreatment levels were found. PMID- 6264866 TI - [Advances in the field of antiviral vaccines]. AB - Some problems concerning the use of antiviral vaccines are reviewed. Particularly various aspects regarding both intensively used vaccines (small-pox, polio and influenza) and selectively used vaccines (measles, mumps, rubella, parainfluenza and Adenovirus) as well as vaccines under testing (anti-V-Z and hepatitis) are evidenced. PMID- 6264867 TI - The effect of some chemicals (MMS, NQNO, furocoumarins, PMA) on endogenous C-type viruses induction from a murine non-producing cell line. PMID- 6264868 TI - [The hepatitis A and B virus markers (anti-HAV, HBsAg, HBsAb, HBeAg, HBeAb) in leprous patients (author's transl)]. AB - The hepatitis A and B virus markers (anti-HAV, HBsAg, HBsAb, HBeAg, HBeAb) were studied in the serum of 25 patients at the leprosy hospital of Messina. Anti-HAV were detected, by RIA in 100% of the patients; by the same method HBsAg was found in 12% and HBsAb in 48% of the cases. In no patient HBeAg was detected by immunodiffusion; on the contrary, HBsAb was found in 4% of the cases. No significant difference between lepromatous and tuberculoid leprosy was found. PMID- 6264870 TI - [Rotavirus infections in the province of Ancona. Sero-epidemiological studies]. PMID- 6264869 TI - [Non-A, non-B hepatitis]. PMID- 6264871 TI - Immunity to poliovirus in a junior high school population in Palermo. PMID- 6264873 TI - The choice of operation for bronchial carcinoids. AB - In a review of the literature, 1,392 patients with bronchial carcinoids were found. Of these, there were 313 patients for whom individual data with regard to type of operation, follow-up period, and outcome were given. Actuarial curves for proportions of patients who had not died of the disease or who had not undergone reoperation for residual disease were constructed for each type of operation. The prognosis up to 20 years after surgical treatment for bronchial carcinoids is excellent. For 15 to 20 years postoperatively, the prognosis after a lobectomy is excellent and after a pneumonectomy, slightly worse. The prognosis after a lung parenchyma-saving operation (wedge or segmental resection and bronchoplastic procedures) is similar to that after a lobectomy up to 7 years postoperatively. After that, the proportion of disease-free patients declines precipitously. At 20 years the difference in comparison with a lobectomy is statistically significant for both wedge or segmental resections and bronchoplastic procedures. Parenchyma saving operations cannot therefore be said to be radical. A policy for decision making at the operating table is formulated. PMID- 6264872 TI - Radionuclide angiocardiography in the diagnosis of congenital heart disorders. AB - Radionuclide angiocardiography provides a noninvasive assessment of cardiac function and blood flow through the heart and lungs. During the past three years, this procedure has been used at the Duke University Medical Center for evaluation of 343 patients with congenital heart disorders. A review of this experience shows tat the resulting data were frequently useful in the surgical management of these patients. In patients with abnormal blood flow patterns, noninvasive imaging of blood flow was useful before and after operative correction. Radionuclide measurements of left-to-right intracardiac shunts were sufficiently accurate for use in the initial evaluation of patients with murmurs and to document the absence of shunt after operative closure of intracardiac septal defects. Moreover, measurements of right-to-left cardiac shunts were of benefit in the management of children with cyanotic heart disease. Measurements of left ventricular function obtained during rest and exercise were most useful in patients with origin of the left coronary artery from the pulmonary artery and in patients with congenital valvular insufficiency. This experience demonstrates that radionuclide angiocardiography provides important measurements of central hemodynamics and cardiac function which are useful in the management of patients with congenital heart disorders. PMID- 6264874 TI - Stop the pendulum. PMID- 6264876 TI - Failure of prolactin infusion to elicit adrenal androgen secretion. PMID- 6264875 TI - Temporal relationship between hCG induced desensitization of LH/hCG responsive adenylyl cyclase and downregulation of LH/hCG receptors in the rat testis. AB - A single s.c. injection of 75 IU of human chorionic gonadotropin (hCG) into adult male rats caused a transient desensitization of the LH/hCG responsive adenylyl cyclase (AC) in membrane particles from rat testis. Two hours after the injection of hCG, LH/hCG responsive AC was reduced by 40%, whereas LH binding was still normal. After 24 hr LH/HCG responsive AC was lost, whereas LH binding only showed a marginal decrease. During the next 2-3 days there was a gradual loss of LH/HCG receptors, which reached a nadir at day 4 (14% of control levels). At day y and 9 following the hCG injection LH/hCG receptors and LH/hCG responsive AC gradually returned towards normal. Fluoride (F-) stimulated AC activity showed only minor changes throughout the period investigated. The initial loss of AC responsiveness to hCG was associated with maximal levels of circulating hCG. However, desensitization persisted for several days after hCG was cleared form the circulation. AC desensitization preceded LH receptor downregulation and may support the notion that uncoupling of the catalytic subunit of the AC from Leydig cell LH/hCG receptors is a requirement for subsequent receptor internalization. PMID- 6264877 TI - Testicular cyclic nucleotide phosphodiesterase in the rat. Kinetic properties and changes with age. AB - The assay for cyclic nucleotide phosphodiesterase has been applied, with certain modifications, to the measurement of the soluble forms of these enzymes in the rat testis. The homogenization and incubation conditions were adjusted to achieve linear product formation as a function of time and protein concentrations and the resulting products were isolated by ion exchange chromatography using 5 mM HCl as the eluting agent. Phosphodiesterase activities were present in the testicular cytosol (105,000 g supernatant) of adult rats which were capable of hydrolyzing cAMP with a high (Km2 microM) and low Km20 microM) affinity and GMP with a relatively high affinity (Km3 microM). The low affinity cAMP enzyme activity could be stimulated with divalent ions such as calcium, magnesium, and manganese. At 18 days of age, all three enzyme activities were present in the testis, although both the high and low affinity cAMP phosphodiesterase displayed maximal rates (Vmax) that were only one third of the adult testis (when expressed per mg protein). PMID- 6264878 TI - Rotavirus. I. Hemagglutination and complement fixation inhibitor antibodies in individuals of Mexico city. AB - Hemagglutination inhibiting antibodies were studied in 1,278 sera of individuals of different ages in Mexico City representative of four different socioeconomic levels. It was found that 1,261 (98.7 per cent) had antibodies against the Nebraska strain (calf rotavirus). An unusual finding was that more than 95 per cent of children from one to four years of age, had antibodies. For this reason five year old children were studied utilizing two viral strains as antigens in hemagglutination inhibition tests. It was found that in 918 sera, 821 (89.4 per cent) had antibodies against SA-11 samples (monkey rotavirus); percentage increased from 87.2 per cent in neonates to 97.5 percent in children from four to five years of age. A similar phenomenon was observed when Nebraska strain hemagglutinin was utilized. Also complement fixation antibodies against SA-11 strain in 583 sera were studied finding that 260 (44.6 per cent) had antibodies. Utilization of this technique showed that seropositivity percentage decreased from 47.6 per cent in the neonate group to 14.5 per cent in the one ot three month old children increasing progressively until reaching 65.1 per cent in children three to four years of age. These results show that rotavirus infection takes place at early ages, as has been confirmed by other authors that have used electron microscopy techniques, RNA electrophoresis, etc., regardless of the presence of transplacental antibodies. PMID- 6264880 TI - [Morphology of coronaviruses-- electron microscopic demonstration by negative contrast technic of the transmissible gastroenteritis virus of swine]. AB - This contribution to the morphology of corona virus is based on the use of electron microscopy in a negative contrast investigation of the virus of transmissible gastroenteritis of swine. Viruses of transmissible gastro-enteritis are spherical or, in rare cases, pleomorphous particles of typical corona virus structure. The viruses investigated by the authors were 132 nm in diameter. The surface projections, consisting of a flattened knob and conical shaft, are 18 nm in length. Internal bodies, 50 +/- 2 nm in diameter, occur as "filled" or "empty" particles. The thickness of all internal bodies and virus membranes is 8 +/- 1 nm. Differences were found to exist between virus of transmissible gastro enteritis and particles similar to corona virus and isolated from faecal samples. A first comparison had been made for that purpose. Those differences were relating to shape and size of individual particles and to morphological setup of surface projections. PMID- 6264879 TI - Rotavirus. II. Viruses associated with acute gastroenteritis in children. AB - Rotavirus was investigated in the feces of 232 children under five years of age with acute infectious gastroenteritis by means of viral RNA electrophoretic technique. 15.1 per cent of cases were positive and no predominance was observed regarding age or seasonal period. Approximately 50 per cent corresponded to one of the two rotavirus types, byt type 2 (2 L) was predominant in the first six months of the year and type 1 (2 S) in the other six. Results are consistent with those obtained by other authors for it is considered that approximately 20 per cent of acute diarrheas during infancy are caused by viral agents. PMID- 6264881 TI - [Use of immunofluorescence technic for the diagnosis of rotavirus infection in the calf]. AB - A methodical account is given of possible applications of the immuno-fluorescence technique in the diagnosis of rotavirus infection of calf. The technique has proved suitable for routine checks for both its low input in terms of method and hardware and its potential of diagnostic information. The two latter methods are best applicable under routine conditions to testing of faeces-inoculated cell cultures as well as to the detection of rotavirus from faecal smears and frozen intestinal sections. In investigations on the dynamics of rotavirus development in cell cultures, the first freshly formed virus protein was detected six hours from inoculation. The time of one replication cycle was found to be between 16 and 18 hours, with several replication cycles running consecutively, when it comes to virus strains which have become adapted to the cell cultures concerned. PMID- 6264882 TI - Levels of angiotensin-converting enzyme in pleural effusion. AB - The value of determining the angiotensin-converting enzyme (ACE) in serum has been clearly established, particularly in sarcoidosis, but is significance in pleural effusions is practically unknown. In the present study, ACE level was determined in the pleural fluid of 18 hospitalized patients along with the values for total protein, lactic acid dehydrogenase (LDH), complete and differential cell counts and cytology. The ACE level was higher in exudates than in transudates and paralleled closely the total protein level in the pleural fluid. There was no correlation between ACE and LDH levels and either WBC or RBC counts in the effusions. The ACE levels failed to discriminate between benign and malignant diseases or to correlate with any specific etiology for the effusion. There was a significant gradient between ACE levels that were higher in the serum than in the effusion of all nine patients in whom both were measured. The filtration coefficient (ratio of pleural fluid to serum concentration of a protein) of ACE was less than that of total protein and was compatible with ACE penetration in the pleural fluid by a process of diffusion. PMID- 6264883 TI - Herpes simplex encephalitis. A modified indirect immunoperoxidase technique for rapid diagnosis in paraffin-embedded tissue. AB - A modification of a reliable and simple method of the indirect immunoperoxidase technique was used to identify herpesvirus antigen in paraffin-embedded tissue of patients with herpes simplex encephalitis (HSE), as well as in rats and mice. So far we have studied five cases in humans and six in mice and rats. With preincubation, we increased antigenicity and accomplished high specificity. Brown reaction product was found mainly at the periphery of the areas of necrotizing encephalitis. Here it was present in different types of glial cells, as well as in neurons. In the animals, it was found in the leptomeninx in cells of the basal cortex and in the ependymal cells of the third ventricle and the cells around it. This method should be of great value for the study of human pathology because new drugs are available for treatment of HSE and a tissue diagnosis is necessary. It is also a useful technique for studying viral CNS infections in experimental animals. PMID- 6264884 TI - False intranuclear inclusions in adrenal cytomegaly. AB - Seventeen cases of adrenal cytomegaly were reviewed. False intranuclear inclusions were noted in 11 cases. In three of them, electron microscopy showed that the nuclear inclusions were composed of the invaginated portion of the cytoplasm surrounded by double membrane and contained numerous organelles. PMID- 6264886 TI - Lumbosacral radioculopathy: review of 100 consecutive cases. AB - Of 100 consecutive patients with acute lumbosacral radiculopathy who were treated conservatively and the majority of whom were followed for at least 5 years, only 5% had to undergo laminectomy and diskectomy. Conservative management included complete bed rest for 2 to 3 weeks, with occasional use of anti-inflammatory drugs, and support of the lumbosacral spine, at first with a corset and later with vigorous abdominal strengthening exercises. Repeated electromyography was of value in assessing clinical weakness, providing objective guidance to management. It is concluded that in only rare instances is surgery indicated for lumbosacral radiculopathy secondary to disk derangement. PMID- 6264885 TI - Cytoplasmic inclusions of Fabry's disease. Ultrastructural demonstration of their presence in urine sediment. AB - The diagnosis of Fabry's disease (angiokeratoma corporis diffusum universale) is usually confirmed by demonstrating typical cytoplasmic inclusions in a renal biopsy specimen, in conjunction with typical skin and ocular lesions and deficient alpha-galactosidase A activity in a male patient. Affected men are usually associated with carrier female family members. Electron microscopy of the urine sediment from two patients with Fabry's disease demonstrated typical laminated cytoplasmic inclusions within exfoliated epithelial cells. This method may be useful in the diagnosis of Fabry's disease and in screening of kin for hemizygotes and female carriers. PMID- 6264887 TI - Clinical polymorphism of diseases caused by non-poliomyelitis enteroviruses. PMID- 6264888 TI - On the main modalities of progression in infections with the HB virus. PMID- 6264889 TI - [Evaluation of ACTH and cortisol in patients suffering from peripheral artery disease]. PMID- 6264890 TI - [Evaluation of blood cortisol and plasma ACTH in patients with gastroduodenal ulcer]. AB - A significant blood cortisol level, unaccompanied by changes in ACTH by comparison with normal controls, was noted in 30 subjects with ulcers. PMID- 6264891 TI - [2 cases of insulinoma]. PMID- 6264893 TI - Recovery of cell-free varicella virus from Vero cells. PMID- 6264892 TI - The RNA of the human syncytium-forming (foamy) virus. AB - Human syncytium-forming (foamy) virus was labeled with 3H-uridine and banded isopycnically in sucrose gradients (buoyant density = 1.16 to 1.18 g/cm3). Viral RNA extracted from the banded virus was analyzed either by rate zonal separation in sucrose gradients or by polyacrylamide-agarose gel electrophoresis. The results indicated that purified HSFV contains a 60S RNA component plus several smaller molecular weight RNA components. On dissociation with heat, smaller RNA structures were released from the 60S component. These results indicate that the genome of HSFV, like the other members of the Retroviridae family, is composed of an aggregate of several RNA species. PMID- 6264894 TI - Iridescent virus type 22 DNA. AB - Double stranded DNA extracted from iridescent virus type (IV 22) was characterized by its buoyant density in CsCl, thermal denaturation profile and guanine plus cytosine content. The DNA was linear with a molecular weight of 130- 142 x 10(6) determined by reassociation kinetics, contour length measurements and restriction endonuclease analysis. PMID- 6264895 TI - Enhancement of antibody activity to bovine leukemia virus by complement. AB - Cocultivation of fetal lamb kidney cells infected with bovine leukemia virus (BLV) and the cat cells containing murine sarcoma virus genome resulted in the rapid production of syncytia. This syncytia formation was inhibited by serum containing antibodies to glycoprotein antigen of BLV. When rabbit complement was added to the antiserum for early syncytia inhibition (ESI) test, a significant enhancement of ESI activity of the antiserum was observed. This enhancement was associated with IgG fraction but not with IgM fraction of the antiserum. The results of the comparative serological tests showed that the ESI test with complement was much more sensitive than either immunodiffusion or complement fixation tests in the detection of BLV antibodies. PMID- 6264896 TI - Contact infection of mink with influenza A viruses of avian and mammalian origin. PMID- 6264898 TI - In vivo selection of two agents differing in hepatoma-inducing activity from strain MC29 avian leukosis virus. AB - MC29 virus induces acute leukemia (myelocytomatosis) and primary tumors of liver (hepatomas) in turkey poults. By in vivo passages two viruses were selected; designated "liver" and "bone marrow" variants, differing in hepatoma-inducing activity. The "liver" variant induces hepatoma and acute leukemia, the "bone marrow" variant induces acute leukemia. The variants differ in leukemogenic activity. The "bone marrow" variant induces high grade leukocytosis, while the "liver" variant causes lymphocytosis and heteropenia. The variants also induce the appearance of primitive myeloid cells in the blood. The kinetics of accumulation of viral gs protein (p27) and the presence of viruses inducing hepatoma and leukemia were studied in organs of infected turkeys. The differences between the variants showed no relationship with their selective reproduction capacity in liver and/or bone marrow cells. The results obtained suggest that different viral particles are responsible for the induction of leukemia and hepatoma. PMID- 6264899 TI - Cyclic nucleotide phosphodiesterase in the aorta of spontaneously hypertensive rats : variation with age and effect of propranolol. AB - The activities of cyclic AMP- and cyclic GMP-phosphodiesterase were studied in the aorta (freed of the adventitia layer) of spontaneously hypertensive rats (SHRs). At the time of weaning (3 weeks of age) young SHRs were separated into two groups. One group was chronically treated with propranolol, 50 mg.kg-1 daily for 4 weeks (treated rats), with treatement beginning either at the time of weaning or at 15 weeks of age. The second group (non-treated SHRs) was used as control. In both groups we observed that the protein content per aorta but not the DNA content increased parallel to the organ weight. The enzyme activities were related to the DNA content of aorta. In non-treated SHRs, the phosphodiesterase activties increased with age, but there was a considerable lag of time between the marked increase in blood pressure that occured between 5 and 12 weeks of age and the increase in phosphodiesterase activity which started after 12 weeks of age. Prolonged propranolol treatment significantly decreased both blood pressure and enzyme activities when started at the time of weaning but had no effect when given to mature SHRs. Thus, the effects of propranolol on blood pressure and on phosphodiesterase activities were associated, whereas no correlation could be established between the age-dependent increases in blood pressure and in phosphodiesterase activities in aorta cells of the SHR. PMID- 6264897 TI - Efficacy of a virion envelope herpes simplex virus vaccine against experimental skin infections in hairless mice. AB - Hairless mice were immunized with herpes simplex virus type 1 (HSV-1) envelope antigen (EAG), EAG in association with polyriboinosinic . polyribocytidylic acid poly-L-lysine complexed with carboxymethylcellulose (PICLC), and inactivated purified HSV-1 (VAG). After 2 weeks the mice were challenged by a percutaneous HSV-1 infection in the orofacial (OF) or lumbosacral (LS) skin area. Following immunization a consistent cell-mediated immune response was observed in all immunized mice, although the humoral immune response was very low, or not detectable. After challenge, a marked secondary humoral and cell-mediated immune response developed in all immunized mice, and the animals were protected against the development of skin lesions and the fatal outcome of infection. However, the establishment of latent infections in the sensory ganglia was not prevented by the immunization procedure. PMID- 6264900 TI - [Time of normal intestinal transit in Peruvian subjects]. AB - Intestinal transit-time (TTI) and daily steel weight (PDH) were determined in 20 Peruvian healthy volunteers, following a universally accepted technique. Mean of TTI (mean +/- s.d.: 60.2 +/- 25.5 h) was similar to the ones reported in subjects, from other world places, who consume refined diets, poor in fibre; while mean of PDH (mean +/- s.d.: 174.5 +/- 114.0 g) compared better to the ones reported in subjects who consume mixed diets, composed by refined foods and foods with a high fibre content. Contrarily to what other authors have observed, correlation between TTI and PDH was not significant (r r0.03, only). The obtained results may be explained by the coexistence of several inconstant determinant factors, among which would be a deficient ingestion of dietary fibre. PMID- 6264901 TI - The effects of cross-circulation and charcoal hemoperfusion on adenylate energy charge of the remnant liver after major hepatic resection. AB - The effect of liver support on the adenylate energy charge (ATP + 1/2 ADP) / (ATP + ADP + AMP) of the remnant liver after major hepatic resection was studied in rabbits. The present study emphasizes the principle of the use of homologous or heterologous liver for preventing the decrease in the energy charge of the remnant liver after major hepatic resection. The energy charge level provides the cell with a very sensitive intracellular control mechanism. Regulatory enzymes from biosynthetic sequences exhibit very little activity at low levels of energy charge, and their activities increase sharply at high charge values. The energy charge level of the remnant liver maximally decreased from the normal level of 0.843 to 0.767 at 24 hours after 70% hepatectomy. The energy charge level increased from 0.767 to 0.828 after one hour of cross-circulation of systemic blood between the 24-hour, 70% hepatectomized rabbit and a normal rabbit. An increase from 0.767 to 0.801 also occurred after one hour of charcoal hemoperfusion. Although either means of liver support serves to restore energy charge levels, the above results suggest that cross-circulation may be more effective than charcoal hemoperfusion for biosynthesis in the regenerative processes of the remnant liver. PMID- 6264902 TI - Lipid analysis in nerve biopsy specimens of hypertrophic neuropathy. AB - We performed a lipid analysis on nerve biopsy specimens in two cases of degenerative hypertrophic neuropathy. Quantitative analysis of the major lipid classes, ie, cholesterol, cerebrosides, sulfatides, ethanolamine phospholipids, phosphatidyl-choline, phosphatidyl-serine, phosphatidyl-inositol, sphingomyelin, and gangliosides, were performed. The two cases exhibited extreme decreases in levels of lipids that could be related to the very low myelin content of these nerves. Cholesterol and phospholipid levels were especially reduced. Cerebrosides and sulfatides were not modified in the same proportion, as could have been predicted from the degree of demyelination. This relative glycolipid increase could be due to the very high Schwann cell proliferation. PMID- 6264903 TI - Pontomedullary vs pontomesencephalic transmission time. A diagnostic aid in multiple sclerosis. AB - Caudal vs rostral transmission time has been studied in patients with multiple sclerosis (MS). In the majority of the cases, prolongation in latency was more severe in the caudal segment, which suggests that this part of the brainstem is more commonly affected in MS. The difference between pontomedullary and pontomesencephalic transmission time yields a variable that may prove a valuable adjunct in the electrodiagnosis of MS. PMID- 6264904 TI - Hypercalcemia secondary to a pseudoparathormone-secreting ameloblastoma. AB - An unusual case of hypercalcemia associated with an ameloblastoma occurred. The sequence of recurring ameloblastoma, increased serum calcium levels and urinary cyclic adenosine monophosphate (cAMP) levels, removal of the tumor, and decrease of those levels to normal suggests that the ameloblastoma was secreting a parathormone-like substance that, in turn, was stimulating the production of nephrogenous cAMP and elevating the serum calcium level. PMID- 6264905 TI - Oat cell carcinoma of larynx. AB - Mucus secretion, cytoplasmic argyrophilia, intracellular lumen, neurosecretory granules, and tonofilaments were observed in a histologic and ultrastructural study of laryngeal oat cell carcinoma. In theories of tumor genesis, more than one line of cellular differentiation is a significant finding. PMID- 6264906 TI - Regression of recurrence of carcinoma of the breast at mastectomy site associated with intensive meditation. PMID- 6264907 TI - Physical analysis of a (dG + dC)-rich fraction of DNA obtained from the ovine genome. AB - Using the organomercuric compound 3,6-bis(acetatomercurimethyl)dioxane in conjunction with Cs2SO4 density gradient equilibrium centrifugation a (dG + dC) rich DNA fraction constituting 10% of the ovine genome was separated from the remainder. Further fractionation allowed four distinct classes of DNA to be identified with buoyant densities in neutral CsCl of 1.714, 1.717, 1.725 and 1.716 g/cm3. Computerized curve resolving of the data indicated the presence of several additional DNA classes. Data obtained using restriction endonuclease digestion indicated that the 1.714 g/cm3 satellite consists principally of an 820 base pair (bp) tandemly repeating unit. The 820-bp DNA is also present in the 1.717 g/cm3 satellites but as a minor component. The principal components of the 1.717 and 1.725 g/cm3 fractions are 125-, 176- and 235-bp fragments. In addition, these fractions contain 705-bp tandemly repeated material. Two or possibly three species of 22-bp tandem repeats were found only in the 1.725 g/cm3 DNA. PMID- 6264908 TI - Amino acid sequence studies on sheep liver fructose-bisphosphatase. I. The S peptide. AB - Fructose-bisphosphatase has been isolated from sheep liver using affinity-elution chromatography from carboxymethylcellulose as the final purification step. The purified enzyme was homogeneous by disc gel electrophoresis. Digestion with subtilisin yielded the N-terminal S-peptide similar to that reported for the rabbit and pig. The peptide has an acetylated amino terminal residue and the following sequence deduced from a study of the tryptic and cyanogen bromide peptides: Ac-Thr-Asp-Glu-Ala-Pro-Phe-Asp-Thr-Asn-Ile-Val-Thr-Val-Thr-Arg-Phe-Val Met-Glu-Glu-Gly-Arg-Lys-Ala-Arg-Gly-Thr-Gly-Glu-Met-Thr-Gln-Leu-Leu-Asn-Ser-Leu Cys-Thr-Ala-Val-Lys-Ala-Ile-Ser-Thr-Ala-Val-Arg-Lys-Ala-Gly-Ile-Ala-His-Leu-Tyr Gly-Ile-Ala. The sheep liver S-peptide sequence shows only six changes in 60 residues and three changes in 56 residues compared with the sequences of the rabbit and pig S-peptides respectively. PMID- 6264909 TI - The glucagonoma syndrome: an unusual skin rash associated with diarrhoea and diabetes. PMID- 6264910 TI - The isolation of two bluetongue viruses from healthy cattle in Australia. PMID- 6264912 TI - [Immunohistologic antigen demonstration and virus isolation in cell cultures in Aujeszky disease]. PMID- 6264911 TI - Myocardial high energy phosphates and function as influenced by di- or trivalent cations and isoproterenol or DBcAMP. AB - The effects of Mn++, La+++ and Co++ (2 mM) with and without ISO or DBcAMP were investigated in isolated perfused rat hearts concerning mechanical and metabolic parameters. Mn++ and La+++ produce cardiac arrest accompanied by unchanged content of high energy phosphates. ISO or DBcAMP resp. administered together with these cations do not exhibit characteristic effects. Co++ induces cardiac arrest as well, but in addition severe reduction of high energy phosphate stores and O2 consumption. The effects of Co++ can be partly prevented by administration of ISO and elevated extracellular Ca++ concentration concerning mechanical parameters and oxygen consumption, whereas high energy phosphate stores remain low. The results obtained demonstrated that the Ca++ antagonistic ions studied show the expected metabolic consequences of EC-uncoupling only in the case of Mn++ and La+++. Co++ ions induce in additions to cardiac arrest and low O2-consumption severe reduction of high energy phosphate stores indicating disturbance of respiratory control of mitochondria. PMID- 6264913 TI - [Experimental studies of the etiology and pathogenesis of atrophic rhinitis in swine. 1. Cytomegalovirus-negative gnotobiotic piglets from seropositive sows]. PMID- 6264914 TI - Proton translocation in hydrogen bonds with large proton polarizability formed between a Schiff base and phenols. PMID- 6264915 TI - Only one type of benzo(a) pyrene-DNA adduct is detected in transformable mouse cells. PMID- 6264916 TI - Inhibition of ADP-ribosylation of histone by diadenosine 5', 5"' -p (1), p(4) tetraphosphate. PMID- 6264917 TI - Thymidine kinase activity in mouse embryo fibroblast cells infected with murine cytomegalovirus. PMID- 6264919 TI - Inhibition of lung cyclic AMP- and cyclic GMP-phosphodiesterases by flavonoids and other chromone-like compounds. PMID- 6264918 TI - Chromatin superstructure: the next level of structure above the nucleosome has an alternating character. A two-nucleosome based series is generated by probes armed with DNAase-I acting on isolated nuclei. PMID- 6264921 TI - Range of environmentally responsive monooxygenase activities in human placental microsomes determined by direct fluorescence techniques. PMID- 6264920 TI - The water-soluble and protein-bound metabolites of benzo(a)pyrene formed by rat liver. PMID- 6264922 TI - Pulmonary metabolism of benzo(a) pyrene : effect of asbestos. PMID- 6264923 TI - Oxidation of isopropanol by rat liver microsomes: possible role of hydroxyl radicals. PMID- 6264924 TI - Polyphosphoinositide metabolism in erythrocytes of spontaneously hypertensive rats. PMID- 6264925 TI - Hydrogen peroxide-supported oxidation of benzo [a]pyrene by rat liver microsomal fractions. PMID- 6264926 TI - Possible muscarinic regulation of catecholamine secretion mediated by cyclic GMP in isolated bovine adrenal chromaffin cells. PMID- 6264927 TI - 'A'-esterase activity in the lipoprotein fraction of sheep serum. PMID- 6264928 TI - Epstein-Barr virus. Its relationship to the pathogenesis of rheumatoid arthritis. PMID- 6264929 TI - The effect of digitalis glycosides-specific antisera on the binding of the glycosides to (Na+ + K+)-ATPase. AB - The capability of digitalis glycoside-specific antisera to reverse the glycoside induced inhibition of (Na+ + K+)-ATPase activity was examined. The antisera induced reversal of the ATPase inhibition caused by digoxin was considerably slower (k-1 = 0.1177 . 10-3 .S-1) than the reversal caused by dihydrodigoxin and dihydrodigitoxin (k-1 = 4.462 . 10-3 . S-1 and K-1 = 3.609 .10-3 . S-1, respectively). In addition, the dissociation rate constants of the ouabain induced dissociation of the various glycosides from the glycoside-ATPase complex were determined: The dissociation rate constants of the antisera-induced restoration of enzyme activity and that of the ouabain-induced dissociation of glycosides from the glycoside-enzyme complex were not significantly different. PMID- 6264930 TI - Organic calcium-antagonists and calcium-ionophores. AB - Verapamil, suloctidil and other organic calcium-antagonists inhibit calcium translocation from an aqueous medium into a hydrophobic domain medicated by 8-[1 (ethyl-1-carboxy-pyrrole-2)]-4-(2-methylene-4-carboxy-5-methylamino-benzoxazole) spiro(5,5)hendecan-3,9,11-trimethyl-6,7-dioxane (A23187). The magnitude of this inhibition depends on the verapamil/ionophore concentration ratio, the slope of the dose-action relationship (in semilogarithmic coordinates) being comparable with distinct drugs of vastly different biological potency. Like in intact cells, calcium-antagonists, an effect which apparently depends on a direct interaction with the calcium-binding site of the ionophoretic molecule. Verapamil also inhibits calcium and sodium translocation mediated by 3-methyl-5-bromo-6(7-ethyl 4-hydroxy-3,5-dimethyl-6-oxo-7-[5-ethyl-3-methyl-5-( 5-ethyl-5-hydroxy-6-methyl-2 tetrahydropyranyl)-2 tetrahydrofuryl] heptyl) salicylic acid (X537A). The relative efficiency of suloctidil and its analogues or metabolites to inhibit calcium translocation correlates with their potency to inhibit smooth muscle contraction. These findings suggest that the interference of organic calcium antagonists with native ionophoretic processes represents a fundamental event in the expression of their biological action. PMID- 6264931 TI - Exploration and motor activity after intraventricular ACTH, morphine and naloxone. AB - Intraventricular injection of morphine (5 microgram) and ACTH (2.5 microgram) reduced the time spent head-dipping and the number of head-dips made by rats during a 10-min trial in a holeboard. These effects were reversed by naloxone (2.0 mg/kg, i.p.), in spite of the fact that naloxone alone also reduced these measures of exploration. None of the drugs or drug combinations tested significantly reduced locomotor activity. The results are discussed in relation to the action of ACTH on opiate receptors. PMID- 6264932 TI - Conditioning of hippocampal cells: its acceleration and long-term facilitation by post-trial reticular stimulation. AB - Neuronal activity, recorded in the dorsal hippocampus (CA3) during classical conditioning, was studied in rats receiving mild post-trial stimulation of the mesencephalic reticular formation. Hippocampal multi-unit activity increased in response to an auditory signal (conditioned stimulus) after pairing of the signal with a footshock (unconditioned stimulus), while the auditory signal alone, presented before conditioning, did not change the rate of hippocampal cell discharges. Trial-by-trial analysis of hippocampal multi-unit responses to the conditioned stimulus, both during acquisition and during a test of long-term retention, indicated that post-trial mesencephalic reticular stimulation hastened the onset of cellular conditioning and facilitated conversion to long-term storage. A study of evoked potentials recorded in the hippocampal formation to stimulation of the perforant path in awake rats, suggested that these effects could be mediated through a modulation of synaptic efficiency within hippocampal neuronal networks. These data are discussed in relation to the concept of neural perseveration in memory consolidation. PMID- 6264933 TI - [Effect of the administration of Cardiostenol on experimental hepatitis in mice induced with MHV-3 virus]. AB - Treatment with Cardiostenol (commercial name of a pharmaceutical product containing morphine chloridrate+atropine+sparteine) does not modify the course of hepatitis in mice infected with MHV-3 virus. Similar results were previously obtained by treatment with morphine chloridrate alone. PMID- 6264934 TI - [Correlation between brain and other organs (author's transl)]. PMID- 6264935 TI - Calcium hydroxide dimer (Cal-mer) cements. PMID- 6264936 TI - Bronchial and cardiac beta-adrenoceptor blockade--a comparison of atenolol, acebutolol and labetalol. AB - Bronchial and cardiac beta-adrenoceptor blockade have been compared in six normal subjects after three beta-adrenoceptor antagonists. Single and double doses of atenolol (50 and 100 mg), acebutolol (100 and 200 mg) and labetalolol (150 and 300 mg) were studied on separate occasions. 2 Salbutamol airway dose-response curves were obtained by measuring the airway response as the change in specific airway conductance (sGaw) after increasing doses of inhaled salbutamol. Bronchial beta-adrenoceptor blockade was assessed after each drug as the dose of salbutamol needed to cause a 50% increase in sGaw (sGaw D50). 3 Cardiac beta-adrenoceptor blockade was assessed after the same doses of each beta-adrenoceptor antagonist, by measuring the percentage reduction in exercise heart rate from control, after exercise for 5 min at 70% of the subject's maximum work rate. 4 Atenolol 50 and 100 mg caused least bronchial beta-adrenoceptor blockade and the greatest reduction in exercise heart rate. 5 Acebutolol 100 and 200 mg and labetalol 150 and 300 mg produced more bronchial beta-adrenoceptor blockade than atenolol. 6 With this approach new beta-adrenoceptor antagonists can be assessed without putting asthmatic patients at risk. PMID- 6264938 TI - Lack of effect of phenytoin on functions related to Na+,K+-ATPase activity of the intact erythrocytes of epileptic patients. PMID- 6264937 TI - The influence of age, smoking and hyperthyroidism on plasma propranolol steady state concentration. AB - 1 Plasma propranolol steady state concentration (Css) was determined during chronic dosage (160 mg/day) in 22 hyperthyroid patients (aged 16-75 years, 11 smokers, 11 non-smokers) and again following treatment when euthyroid. 2 There was a positive correlation between plasma propranolol Css and age in patients both when hyperthyroid (r = 0.74, P less than 0.01) and when euthyroid (r = 0.58, P less than 0.05). 3 Plasma propranolol Css in hyperthyroid patients were lower (P less than 0.05) in smokers than in non-smokers. 4 Following correction of hyperthyroidism there was a significant increase (P less than 0.01) in both the plasma propranolol Css and degree of plasma protein binding of propranolol. 5 Hyperthyroidism and smoking are known to increase the rate of drug metabolism and it is suggested that these variables may give rise to or accentuate an age related reduction in propranolol clearance. PMID- 6264939 TI - HLA frequency and prognosis in lung cancer. AB - In 100 patients with lung cancer we have found no significant abnormality in overall HLA antigen frequency when compared to a control sample of 151 random health individuals from the same region, though there was a high relative risk of being HLA-BW22-positive and having lung cancer. There was an increased frequency of HLA-B5 in small-(oat-)cell anaplastic carcinomas (P less than 0.05); HLA-B15 in anaplastic tumours (P less than 0.05); HLA-B40 in Stage III patients (P = 0.05) and a decreased frequency of HLA-B12 in adenocarcinomas (P less than 0.05). In 86 patients followed up for 2 1/2-5 3/4 years after surgery we have been unable to confirm the significant association of HLA-AW19 and/or HLA-B5 with good prognosis as reported by others. The most striking observation was that the frequency of HLA-BW22 was significantly higher in patients alive at least 2 1/2 years after surgery when compared to the control groups (P less than 0.05) and 83% of patients HLA-BW22-positive are alive compared to only 52.5% of lung cancer patients lacking this antigen. However, all the P values become nonsignificant when multiplied by the number of antigens studied, and these observations need further investigation in a large, prospective study. PMID- 6264940 TI - Immunofluorescent detection of hormone receptors in cutaneous melanocytic tumours. AB - Immunofluorescent assessment of hormone receptors in melanocytic tumours is quite feasible without loss of diagnostic material, in contrast to the impracticability of quantitative biochemical assays. Using this method, oestrogen receptors were demonstrated in 4/6, and progesterone receptors in 3/5 patients with metastatic melanoma. Receptors were not found in 3 patients with primary cutaneous melanomas of the superficial spreading type. Progesterone receptors were present in the junctional component of a naevus from one healthy person. PMID- 6264942 TI - Growth of herpes simplex virus types 1 and 2 in tissues of fertile hens' eggs in ovo and in vitro. AB - The growth characteristics of herpes simplex virus Types 1 and 2 were examined on the chorioallantoic membrane of the fertile hen's egg and in cell cultures derived from egg and embryo tissues. After chorioallantoic membrane inoculation, the yield of infectious Type 1 virus was highest at 2 days and declined rapidly thereafter. With the Type 2 virus replication continued longer, titres were higher, and these declined more slowly over the 7-day incubation period. In cell cultures derived from embryo tissues, both virus types multiplied well, but Type 1 gave consistently higher titres of infectious virus. Type 2 virus produced higher titres in chorioallantoic membrane-derived cell cultures than did Type 1, reflecting the findings in ovo. Temperature-marker tests in eggs showed that fresh isolates of Type 1 virus grew less readily at elevated temperatures than those of Type 2 or laboratory-adapted Type 1 strains. There was no difference in the capacity of laboratory strains of either type to grow in eggs at these temperatures. PMID- 6264943 TI - The presumptive diagnosis of primary cytomegalovirus infection in early pregnancy by means of a radioimmunoassay for specific-IgM antibodies. AB - During a 30 month investigation 3633 women were studied when the booked for antenatal care. Complement fixing antibodies against cytomegalovirus (CMV) were detected in 2078 (57 per cent) of the women and these sera were further tested for the presence of specific IgM antibodies by means of a solid-phase radioimmunoassay. Since specific IgM antibodies have previously been shown to persist for up to four months after primary CMV infection, their presence in a booking serum sample (mean gestation 15 weeks) was taken as presumptive evidence of a first trimester primary CMV infection. From theoretical considerations, 11.6 positive CMV-IgM reactions were predicted in these women and 11 were observed. A highly significant (p less than 0.001) excess of fetal death was seen in the infected women since three pregnancies ended in missed abortion (15 weeks), intrauterine death (29 weeks) and spontaneous abortion (24 weeks) whilst the remaining 8 women gave birth to apparently normal babies. Cord sera were available from 5 of the surviving babies and only one contained specific IgM antibodies, showing that transplacental spread of the maternal infections had not occurred in 4 of the 5 survivors. PMID- 6264941 TI - Modification of tumour and host response to cyclophosphamide by misonidazole and by WR 2721. AB - The effect has been studied of adding either misonidazole (MISO) or the radioprotective drug, WR 2721, to cyclophosphamide (CY) treatment of mice bearing either the RIF-1 or KHT sarcomas. In RIF-1, the growth delay due to CY was increased by the addition of 1 mg/g of MISO. At doses below 75 mg/kg of CY, the effect was dose modifying but, at higher doses, the curves were parallel. When the MISO dose was reduced to 0.33 mg/g, the effect was reduced but not entirely lost. Only a small enhancement of CY response in the KHT tumour was seen with single doses, but the enhancement was greater with fractionated doses. The growth delay produced by CY in both tumour systems was reduced if WR 2721 (400 mg/kg) was given 30 min earlier. At a CY dose of 75-100 mg/kg the dose-modifying factor (DMF) was approximately 0.7-0.8 but, at least in the RIF-1 tumour, was not so low at higher doses of CY. Determination of the LD50 for CY showed a DMF of approximately 1.2-1.3 for MISO (0.33 mg/g) and approximately 0.8 for WR 2721 (400 mg/kg). Neither modifying agent appeared to cause any consistent change in the pattern of body-weight loss after CY, but WR 2721 reduced the myelosuppression seen at 3-4 days after CY. The data suggest that modification of tumour response to CY by the addition of MISO varies from tumour to tumour, and is very dependent upon the MISO dose. The protective effect of WR 2721 when combined with CY is not confined to normal tissues, and at a dose of 400 mg/kg may be as great in terms of tumour response as in terms of acute LD50 in this system. At a lower dose of WR 2721, however, some differential protection may occur. PMID- 6264944 TI - Insulin-induced hypoglycaemia in diabetic women during late pregnancy and one year post partum. AB - Insulin (0.1 IW/kg) later followed by glucose was injected intravenously in nine diabetic women in the supine position both during pregnancy and one year post partum. C-peptide was present in five subjects, indicating some residual beta cell function. Their mean basal C-peptide level, before insulin, was twice as high in the pregnant as inthe non-pregnant state. C-peptide decreased progressively after insulin. The mean basal plasma glucose level was lower during pregnancy (4.8 mmol/l) than after it (9.6 mmol/l), but decreased to the same level (2.2 mmol/l) after insulin. The rate of fall in glucose was thus lower during pregnancy (kt = 2.54) than after (kt = 4.08), but was unrelated to the basal glucose levels. Basal levels of free fatty acids (FFA), 3-hydroxybutyrate (3-HB), cyclic AMP, and lactate were similar, while glycerol was lower during pregnancy. Insulin-induced changes in FFA, glycerol, 3-HB, cyclic AMP, and lactate were similar during and after pregnancy. Plasma amino acid concentrations were generally lower in pregnancy, significantly so only for arginine and glycine. Amino acid levels were unaffected by insulin in pregnancy, whereas leucine, isoleucine and tyrosine decreased significantly in the non-pregnancy, whereas leucine, isoleucine and tyrosine decreased significantly in the non pregnancy, whereas leucine, isoleucine and tyrosine decreased significantly in the non-pregnancy state. We conclude that there are differences in metabolic responses to insulin in diabetic women during and after pregnancy, indicating a decreased sensitivity to insulin during pregnancy in some tissues. PMID- 6264945 TI - Fluorescence studies of dipalmitoylphosphatidylcholine vesicles reconstituted with the glycoprotein of vesicular stomatitis virus. AB - The vesicular stomatitis virus glycoprotein (G) was reconstituted into dipalmitoylphosphatidylcholine (DPPC) vesicles by detergent dialysis. The DPPC gel to liquid-crystalline phase transition of the DPPC-G protein vesicles was monitored by the fluorescence anisotrophy of trans-paranaric acid, 16-(9 anthroyloxy)palmitoylglucocerebroside, 1,6-diphenyl-1,3,5-hexatriene, and 4 heptadecyl-7-hydroxycoumarin. The DPPC transition temperature measured by all four fluorescent probes was lowered in the presence of the G protein and the DPPC gel state was disordered by the G protein as evidenced by a decreased fluorescence anisotropy for all four probes below the phase-transition temperature. A possible ordering of the DPPC liquid-crystalline state by the G protein was indicated by an increased anisotropy of trans-paranaric acid and 16 (9-anthroyloxy)palmitoylglucocerebroside in the liquid-crystalline state of DPPC G protein vesicles. The G protein in addition affected the ionization of the 4 heptadecyl-7-hydroxycoumarin in lipid vesicles, increasing the apparent pK of the probe from 9.05 to 9.45. PMID- 6264947 TI - 35-GHz (Q-band) saturation transfer electron paramagnetic resonance studies of rotational diffusion. AB - The extension of saturation transfer electron paramagnetic resonance spectroscopy (ST-EPR) to an observational frequency of 35 GHz (Q band) is described. At this frequency the spectral resolution is greatly enhanced over that afforded at the 9.5-GHz (X-band) frequency used in most of the ST-EPR studies published to date. Thus, Q-band operation may provide an approach for the detailed analysis of the slow anisotropic motions believed to occur in many biomolecular systems. The spectral characteristics and the effects of various instrumental settings are described in detail for a model system of spin-labeled hemoglobin in water glycerol solutions. Several spectral parameters are defined, and their potential use in monitoring various types of anisotropic motion is considered. PMID- 6264946 TI - Ribonucleic acid splicing in Neurospora Mitochondria: secondary structure of the 35S ribosomal precursor ribonucleic acid investigated by digestion with ribonuclease III and by electron microscopy. AB - In Neurospora, the gene encoding the mitochondrial large (25S) ribosomal ribonucleic acid (rRNA) contains an intervening sequence of approximately 2.3 kilobases (kb). We have identified two temperature-sensitive mutants (289-67 and 299-9) which are defective in a factor encoded by a nuclear gene but required for the splicing of 25S RNA. When grown at the nonpermissive temperature (37 degrees C), the mutants accumulate a novel 35S RNA (5.2-5.6 kb) which is related to the natural precursor of 25S RNA and which has been shown to be a collinear transcript of the 25S RNA gene including the intervening sequence. In the present work, the secondary structure of 35S RNA was investigated by digestion with ribonuclease III and by electron microscopy of the RNA spread under partially denaturing conditions. Ribonuclease III cleaves 35S RNA predominantly at a central site or sites near the 5'-intron-exon boundary and produces fragments which correspond roughly to half-molecules (2.5-3 kb). Electron microscopy of 35S RNA shows a relatively large, central hairpin (180 +/- 45 nucleotides), which presumably corresponds to the central ribonuclease III site, and few other secondary structure features. Both experimental approaches indicate that the large hairpin is not present in 35S RNA. From this finding and from the location of the hairpin near the 5'-intron-exon boundary in 35S RNA, we infer that its formation requires intron sequences. 35S RNA from the mutants can be isolated as a ribonucleoprotein particle associated with almost the full complement of large subunit ribosomal proteins. The 35S RNA in such particles can be cleaved by ribonuclease III at the central site(s), consistent with the idea that the central hairpin is accessible to RNA-processing enzymes in vivo. PMID- 6264948 TI - Interaction of the activated cytoplasmic glucocorticoid hormone receptor complex with the nuclear envelope. AB - Highly purified activated cytoplasmic glucocorticoid hormone receptor binds with high affinity to sites in the nuclear envelope. Nuclear envelope fragments can be isolated from purified chromatin. They bind activated cytoplasmic glucocorticoid receptor with the same equilibrium constant as nuclear envelopes. The presence of envelope components in chromatin is confirmed by the virtual identity of the gel electrophoretic glycoprotein pattern of nuclear envelope, chromatin nonhistones, and nuclear envelope fragments from chromatin. PMID- 6264949 TI - Repeated deoxyribonucleic acid clusters in the chicken genome contain homologous sequence elements in scrambled order. AB - Part of the repeated deoxyribonucleic acid (DNA) in the chicken genome had a clustered organization. The following description of clustered repeated sequences is derived both from analysis of DNA segments cloned in lambda and from hybridization of individual cloned sequences to Southern blots of restricted total DNA. A cluster usually exceeds 20 kbp in length and consists principally, if not entirely, or repetitive DNA. Each cluster contains one cope of several different repeated sequences. The individual sequences occur several hundred times in the genome, but only once per cluster. Many of the clusters contain the same assortment of sequences but in scrambled order. In the genome, those repeated sequences that are elements of clusters occur mainly within the clustered context and are seldom, if ever, found as isolated elements flanked by nonrepeated DNA. These aspects of cluster organization suggest that the clustered sequences undergo limited rearrangement, maintaining the associations within clusters but allowing variability of sequence arrangement from cluster to cluster. The clusters that occupy the cloned DNA segments together represent at least 10% of the repetitive DNA of the chicken. PMID- 6264950 TI - Messenger ribonucleic acid specificity in the inhibition of eukaryotic translation by double-stranded ribonucleic acid. PMID- 6264951 TI - Dynamical and temperature-dependent effects of lipid-protein interactions. Application of deuterium nuclear magnetic resonance and electron paramagnetic resonance spectroscopy to the same reconstitutions of cytochrome c oxidase. AB - 2H NMR and EPR spectra have been obtained as a function of temperature and protein concentration from the same samples of beef heart cytochrome c oxidase reconstituted into 1-(16,16,16-trideuteriopalmitoyl)-2-palmitoleoyl-sn-glycero-3 phosphocholine. At all temperatures, the EPR spectra show the characteristic "bound" and "free" components, while the 2H NMR spectra show only a narrow distribution of orientational order parameters. At temperatures near the phase transition of the pure lipid, the dependence of the 2H NMR average orientational order on protein concentration fits a two-stage model in which the phospholipid molecular exchange rapidly between two states tentatively identified as sites either on or off the protein surface. From this model, the 2H NMR spectra yield a value of 0.18 mg of phospholipid per mg of protein as necessary to cover the surface of cytochrome c oxidase, which is the same value as derived from the EPR spectra at -20 degrees C. Both the 2H NMR and EPR spectra vary markedly with temperature. At temperatures well above the phase transition of the pure lipid, the average orientational parameters derived from the 2H NMR spectra are independent of protein concentration and are the same as for the lipid alone. Qualitatively, the EPR spectra show large apparent decreases in the average orientational order with increasing temperature. Analysis of 2H NMR relaxation rates indicates an additional motion in the presence of protein with a correlation time of 10(-6)-10(-7) s. If this new motion is associated with exchange between the two states, a minimum value of 10(6)-10(7) s-1 for the exchange rate is obtained, assuming that the lipids on the protein surface are much more motionally restricted than the rest of the lipid. Such an exchange rate is compatible with the observed differences in 2H NMR and EPR spectra. These results are consistent with short-lived, energetically weak interactions between cytochrome c oxidase and the phospholipids used in this study. PMID- 6264952 TI - Cytochrome c oxidase. Towards a clarification of its structure, interactions and mechanism. PMID- 6264954 TI - Factors governing substrate-induced generation and extrusion of protons in the yeast Saccharomyces cerevisiae. AB - Experiments with respiration deficient (rho-), ADP/ATP transport deficient (op1) and double (op1 rho-) mutants, with glycolytic and tricarboxylic acid cycle substrates showed that the substrate-induced acidification of yeast suspensions is closely associated with glycolysis. The glucose/proton stoichiometry is 2.5 : 1 to 4 : 1 depending on glucose concentration. The kinetics of the process are complex, the acidification curve having a very fast initial component and two slower exponential components. The first component suggests an initial proton efflux from endogenous sources, triggered by exogenous substrates. The acidification process exhibits two Km values at about 1 and 15 mM D-glucose, indicating two distinct saturable pathways of proton extrusion. The total extent of acidification and thus the final pHout reaches a saturation value with increasing glucose concentration and suspension density. Both the total extent and the rate of acidification are subject to control by extracellular pH which reflects the tendency of the cells to build a fixed [H+]out/[H+]in ratio. When the control is lifted, both quantities are considerably increased. A crucial role in the substrate-induced acidification is thus played by active membrane processes and their control mechanisms. PMID- 6264953 TI - Phospholipid interactions with cytochrome P-450 in reconstituted vesicles. Preference for negatively-charged phosphatidic acid. PMID- 6264955 TI - Processes involved in the creation of buffering capacity and in substrate-induced proton extrusion in the yeast Saccharomyces cerevisiae. AB - The high pH-maintaining capacity of yeast suspension after glucose-induced acidification, measured as its ability to neutralize added alkali, was found to be due mainly to actively extruded acidity (H+). The buffering action of passively excreted metabolites (CO2, organic acids) and cell surface polyelectrolytes contributed only 15--40% to the overall pH-maintaining capacity which was 10 mmol NaOH/l per pH unit between pH 3 and 4 and 3.5 nmol NaOH/l per pH unit between pH 4 and 7. The buffering capacity of yeast cell-free extract was still higher (up to 4.5-times) than that of glucose-supplied cell suspension; addition of glucose to the extract thus produced considerable titratable acidity but negligible net acidity. The glucose-induced acidification of yeast suspension was stimulated by univalent cations in the sequence K+ greater than Rb+ much greater than Li+ congruent to Cs+ congruent to Na+. The processes participating in the acidification and probably also in the creation of extracellular buffering capacity include excretion of CO2 and organic acids, net extrusion of H+ and K+ (in K+-free media; in K+-containing media this is preceded by an initial rapid K+ uptake), and movements of some anions (phosphate, chlorides). The overall process appears to be electrically silent. PMID- 6264956 TI - Ion transport through hemocyanin channels in oxidized cholesterol artificial bilayer membranes. AB - Incorporation of molluscan hemocyanins, obtained either from the blood of Megatura crenulata or Paludina vivipara, into oxidized-cholesterol black lipid films results in the formation of ionic channels. Channel conductance depends on the type of electrolyte present, ranging in our experiments from about 20 to 500 pS. It rises in a non-linear way as the salt concentration is increased, showing a saturation effect. An observed pH dependence of channel conductance suggests that there is a negative fixed charge associated with the pore. We discuss a model based on a simplified form of the Gouy-Chapman theory of the electrified double layer to explain the experimental results. PMID- 6264957 TI - Polymyxin interaction with negatively charged lipid bilayer membranes and the competitive effect of Ca2+. AB - The binding of cationic polymyxin-B to negatively charged phosphatidic acid and phosphatidylglycerol membranes has been investigated by fluorescence polarization study. Competition experiments with Ca2+ were performed. 1. Binding of polymyxin B to mixed dipalmitoylphosphatidic acid/distearoylphosphatidylcholine membranes leads to a phase separation. Domains of polymyxin-bound phosphatidic acid are formed. 2. Ca2+ is found to be a strong competitor in displacing polymyxin from the complex in the mixed membrane system. Complete displacement is obtained at pH 9.0. With decreasing pH value, Ca2+ becomes a less strong competitor and is ineffective at pH 5.0. 3. Binding of polymyxin to dipalmitoylphosphatidylglycerol membranes is observed. Incorporation of polymyxin lowers the lipid phase transition by 10 degrees C. One polymyxin is found to bind five phosphatidylglycerol molecules. The binding curve is determined and in contrast to phosphatidic acid membranes, a noncooperative binding could be established. 4. Addition of Ca2+ decreases the amount of phosphatidylglycerol bound to polymyxin by about 20%. No complete displacement is achieved even at 10-fold excess of Ca2+ with respect to phosphatidylglycerol. PMID- 6264958 TI - Distinct states of lipid mobility in bovine rod outer segment membranes. Resolution of spin label results. AB - Freely diffusable lipid spin labels in bovine rod outer segment disc membranes display an apparent two-component ESR spectrum. One component is markedly more immobilized than that found in fluid lipid bilayers, and is attributed to lipid interacting directly with rhodopsin. For the 14-doxyl stearic acid spin label this more immobilized component has an outer splitting of 59 G at 0 degrees C, with a considerable temperature dependence, the effective outer splitting decreasing to 54 G at 24 degrees C. Spin label lipid chains covalently attached to rhodopsin can also display a two-component spectrum in rod outer segment membranes. In unbleached, non-delipidated membranes the 16-doxyl stearoyl maleimide label shows an immobilized component which has an outer splitting of 59 G at 0 degrees C and a considerable temperature dependence. This component which is not resolved at high temperatures (24--35 degrees C), is attributed to the lipid chains interacting directly with the monomeric protein, as with the diffusable labels. In contrast, in rod outer segment membranes which have been either delipidated or extensively bleached, a strongly immobilized component is observed with the 16-doxyl maleimide label at all temperatures. This immobilized component has an outer splitting of 62--64 G at 0 degrees C, with very little temperature dependence (61--62 G at 35 degrees C), and is attributed to protein aggregation. PMID- 6264959 TI - mit-Mutations in the structural gene of subunit III of cytochrome oxidase in Saccharomyces cerevisiae. AB - Two-dimensional electrophoretic analysis of the mitochondrial translation products of four mit-mutants indicate that subunit III of cytochrome oxidase is the only mitochondrial translation product affected by mutations in the oxi2 region of the mtDNA. Mitochondria of two of these mutants synthesize new products which coprecipitate with an anticytochrome oxidase antiserum and produce proteolytic digests similar to those of subunit III of the enzyme complex. These data strongly support the suggestion that the oxi2 region of the yeast mtDNA contains the structural gene of subunit III of cytochrome oxidase. PMID- 6264960 TI - Purification and characterization of two cyclic AMP-independent casein/glycogen synthase kinases from rat liver cytosol. AB - Two cyclic AMP-independent protein kinases (ATP: protein phosphotransferase, EC 2.7.1.37) (casein kinase 1 and 2) have been purified from rat liver cytosol by a method involving chromatography on phosphocellulose and casein-Sepharose 4B. Both kinases were essentially free of endogeneous protein substrates and capable of phosphorylating casein, phosvitin and I-form glycogen synthase, but were inactive on histone IIA, protamine and phosphorylase b. They were neither stimulated by cyclic AMP, Ca2+ and calmodulin, nor inhibited by the cyclic AMP-dependent protein kinase inhibitor protein. The casein and glycogen synthase kinase activities of each enzyme decreased at the same rate when incubated at 50 degrees C. Casein kinase 1 and casein kinase 2 showed differences in molecular weight, sensitivity to KCl, Km for casein and phosvitin and Ka for Mg2+, whereas their Km values for ATP and I-form glycogen synthase were similar. The phosphorylation of glycogen synthase by these kinases correlated with a decrease in the +/- glucose 6-phosphate activity ratio (independence ratio). However, casein kinase 1 catalyzed the incorporation of about 3.6 mol of 32P/85000 dalton subunit, decreasing the independence ratio from 83 to about 15, whereas the phosphorylation achieved by casein kinase 2 was only about 1.9 mol of 32P/850000 dalton subunit, decreasing the independence ratio to about 23. The independence ratio decrease was prevented by the presence of casein but was unaffected by phosphorylase b. These data indicate that casein/glycogen synthase kinases 1 and 2 are different from cyclic AMP-dependent protein kinase and phosphorylase kinase. PMID- 6264962 TI - Regulation of cytosol 5'-nucleotidase by adenylate energy charge. AB - In the physiological range of the adenylate energy charge in liver (0.7-0.9), th rate of AMP-hydrolysis catalysed by rat liver cytosol 5'-nucleotidase (5' ribonucleotide phosphohydrolase, EC 3.1.3.5) increased sharply with decreasing energy charge. In addition, a decrease in the concentration of Pi caused marked acceleration of the AMP-hydrolysing activity over the physiological range of adenylate energy charge. These responses seem to serve to protect the cells against a metabolic stress which could result from sudden utilization of ATP by removal of AMP. The AMP-hydrolysing activity of this enzyme decreased sharply as the size of the adenine nucleotide pool decreased in the physiological range. This effect may be a self-limiting response to prevent excess depletion of the pool. IMP-hydrolysing activity of this enzyme increased with increasing adenylate energy charge. But no marked response to its variation within the physiological range was observed. On the basis of the data obtained in this study, the IMP hydrolysing activity of the cytosol 5'-nucleotidase in rat liver cells seems to be comparable to that of AMP deaminase reaction, but the AMP-hydrolysing activity was estimated to be less than 10% of AMP deaminase reaction at energy charge value of about 0.7. This strongly suggests that the AMP leads to IMP leads to inosine pathway is more significant that the AMP leads to adenosine leads to inosine pathway in rat liver. PMID- 6264961 TI - Exogenous, but not endogenous, cyclic GMP reduces hepatic pyruvate kinase activity. AB - We investigated the effects of exogenous cyclic GMP and stimulants of endogenous cyclic GMP accumulation on L-form (hepatic) pyruvate kinase (ATP: pyruvate 2-O phosphotransferase, EC 2.7.1.40) activity in isolated rat hepatocytes. Exogenous cyclic GMP (200 muM) reduced pyruvate kinase activity, but was less potent than exogenous cyclic AMP (50 muM) (Ki congruent to 120 muM vs. 30 muM, respectively), had a slower onset of action (1.0 vs. 0.3 min, respectively) and a less rapid maximal effect (5.0 vs. 1.0 min, respectively). Similar results were noted with dibutyryl cyclic GMP or dibutyryl cyclic AMP. 1.0 muM acetylcholine increased cyclic GMP concentrations in isolated hepatocytes from 233 +/- 16 to 447 +/- 3 pmol/g cell protein (P less than 0.001), but did not alter pyruvate kinase activity. Similar results were noted with carbamylcholine, NaN3 or acetylcholine plus eserine sulfate. The results suggest a differential effect of exogenous vs. endogenous cyclic GMP on L-form pyruvate kinase activity, and question the physiological relevance of observations with exogenous cyclic GMP in this system. PMID- 6264963 TI - A calcium-activated protease possibly involved in myofibrillar protein turnover. Isolation of a low-calcium-requiring form of the protease. AB - Two forms of calcium-activated neutral protease were isolated and purified from porcine skeletal muscle. The two forms of the protease differ markedly in their requirement for calcium with the low-calcium-requiring form showing one-half maximal activation at 45 micro M calcium while the high-calcium-requiring form shows one-half maximal activation at 0.74 micro M calcium. Additionally, they chromatograph differently on DEAE-cellulose, exhibit different mobilities in electrophoresis in a nondenaturing buffer, are affected differently by certain divalent cations, and have slightly different pH dependencies. Despite these differences, the purified forms of the calcium-activated protease co chromatograph in gel permeation chromatography, have identical banding patterns on sodium dodecyl sulfate (SDS)-polyacrylamide gels, cross-react with an antibody directed against the 80 000-dalton subunit of the calcium-activated protease we originally purified from skeletal muscle (Dayton, W.R., Goll, D.E., Zeece, M.G., Robson, R.M. and Reville, W.J. (1976) Biochemistry 15, 2150-2158), and have identical effects on the ultrastructure of myofibrils. THe high-calcium-requiring protease purified in this study is very likely identical to the calcium-activated protease we originally purified from skeletal muscle. The properties of the low calcium-requiring form of the protease suggest that it is the form of the enzyme that is active in vivo. PMID- 6264964 TI - Separation and characterization of the membrane-bound and aqueously dispersed phosphatidate phosphatidic acid phosphohydrolase activities in rat lung. PMID- 6264965 TI - The reverse reaction of cholinephosphotransferase in rat brain microsomes. A new pathway for degradation of phosphatidylcholine. AB - The synthesis of phosphatidylcholine is catalyzed by cholinephosphotransferase (EC 2.7.8.2) which is known to be reversible in liver. The reversibility of cholinephosphotransferase in rat brain in demonstrated in this paper. Labeled microsomes were prepared from young rats which had been given an intracerebral injection of labeled choline or oleate 2 h before killing. During incubation of choline-labeled microsomes with CMP, label was lost from ;choline glycerophospholipids and labeled CDPcholine was produced. The Km for CMP was 0.35 mM and V was 3.3 nmol/min per mg protein. Neither AMP nor UMP could substitute for CMP. Oleate-labeled microsomes were pretreated with e mM diisopropylfluorophosphate (lipase inhibitor). During incubation with CMP, label was lost from choline, and ethanolamine glycerophospholipid and labeled diacylglycerols were produced. When the lipase was not inhibited, labeled oleate was produced. We propose that a principal pathway for degradation of phosphatidylcholine, particularly during brain ischemia, is by reversal of cholinephosphotransferase, followed by hydrolysis of diacylglycerols by the lipase. PMID- 6264966 TI - Optimal assay and subcellular location of phosphatidylglycerol synthesis in lung. AB - Synthesis of phosphatidylglycerol from CDPdiacylglycerol and glycerol 3-phosphate by membranous subcellular fractions of rat lung and liver was optimal when assayed in the presence of bovine serum albumin and Triton X-100. Specific activities of glycerolphosphate phosphatidyltransferase in all membranous subcellular fractions of lung were several times higher than the corresponding fractions from liver. Distribution of this enzyme in subcellular fractions of lung or liver closely parallel the activity of the mitochondrial enzymes monoamine oxidase and succinate cytochrome c reductase. The phosphatidylglycerol synthesizing activity in microsomes of both lung and liver was a minor fraction of total tissue activity and could be interpreted as due either to contamination with outer mitochondrial membrane or to a small amount of activity innate to microsomes. These results suggest that phosphatidylglycerol, which is believed to be a component of pulmonary surfactant, is synthesized by lung at a rapid rate relative to liver and that the subcellular distribution of its synthesis is similar in both tissues, with mitochondria as the major site. PMID- 6264967 TI - Phosphatidylinositol-inositol exchange in a rabbit lung. AB - A microsomal fraction prepared from rabbit lung tissue was found to catalyze CDPdiacylglycerol-independent incorporation of [3H]inositol into phosphatidylinositol. This incorporation resulted from CMP-dependent phosphatidylinositol-inositol exchange and did not constitute a net synthesis of phosphatidylinositol. The phosphatidylinositol-inositol exchange activity was distinct from the phospholipid-base exchange enzymes and was specific for inositol. Optimal in vitro phosphatidylinositol-inositol exchange activity was observed at pH 8.5--8.8 and either Mn2+ or Mg2+ was essential for activity. Mercaptoethanol stimulated phosphatidylinositol-inositol exchange and Hg2+ inhibited this activity. In the absence of CMP, no phosphatidylinositol-inositol exchange was observed. CDP (and to a smaller extent CTP) also supported phosphatidylinositol-inositol exchange and this appeared to occur via the generation of CMP during incubations. The apparent Km values of the phosphatidylinositol-inositol exchange enzyme for CMP and inositol were 0.4 mM and 11 microM, respectively. When CDPdiacylglycerol was present at a concentration optimal for CDPdiacylglycerol : inositol transferase activity, CMP dependent phosphatidylinositol-inositol exchange activity was still observed. However, in the presence of Hg2+ CDPdiacylglycerol inhibited phosphatidylinositol inositol exchange activity. Several properties of the phosphatidylinositol inositol exchange enzyme resemble those of CDPdiacylglycerol : inositol transferase, but the two enzymes appear distinct on the basis of different degrees of inhibition by either Ca2+, Hg/+ or heat, and on the basis of different changes in activity during lung development. PMID- 6264968 TI - [DNA immobilization on modified inorganic sorbents]. AB - Fragments of denaturated DNA having the length of about 500 nucleotides were immobilized, using silica carriers modified by organic polymers. It was shown that the organic coating allows to obtain sorbents, which practically exclude non specific sorption with respect to DNA. The immobilization was carried out on hydroxyl-containing sorbents and on their phrosphorylated derivatives by means of water-soluble carbodiimide. The resulting preparations contained up to 60 units at A260 of DNA per 1 g of carrier. The effects of endonuclease A236, exonuclease A5 and pancreatic DNAse on the immobilized RNA were studied. PMID- 6264969 TI - [Effect of the polycationic antibiotic polymyxin B on the respiratory activity of rat liver mitochondria]. AB - the mechanism of the effect of the peptide antibiotic polymixin B on respiration of rat liver mitochondria was studied. It was shown that polymixin B at concentrations of (1,6--2,0) . 10(-3) M inhibits mitochondrial respiration in state 3 and 3u irrespective of the oxidation substrate used and activates oxygen consumption in state 4 at lower concentrations. It is assumed that the antibiotic affects mitochondrial respiration by changing the ionic permeability of the membranes. PMID- 6264970 TI - [Some properties of cotton plant phytase]. AB - Some properties of phytase from cotton plant seeds were studied. The phytase activity was shown to increase during seed germination. The enzyme from cotton sprouts is not activated by Ca2+, Mg2+ and K+ and has the pH optimum of 5,0 and temperature optimum of 50 degrees. The molecular weight of the enzyme as determined by gel-filtration is 36000. PMID- 6264971 TI - [Phospholipid composition of mitochondria and microsomes from some transplantable rat tumors]. AB - The phospholipid compositions of mitochondria and microsomes from rat liver, kidney, nephroma RA and sarcoma 45 were investigated. The "lipid dedifferentiation" of hepatoma membranes found earlier was shown to extend also to other tumours. However, this phenomenon may concern some, but not all phospholipids. PMID- 6264973 TI - [Adenylate cyclase activity and cyclic nucleotide content in human adrenal tumors under Icenko-Cushing syndrome]. AB - The adenylate cyclase activity and cyclic nucleotide content in excised human adrenal tumours (Icenko-Cushing syndrome) were determined. The experimental data were compared to those obtained for hyperplastic adrenals. All adrenal tumours under study revealed a decreased cAMP level, an increased cGMP level and a resulting decrease of the cAMP/cGMP ratio. In malignant adrenal tumours the adenylate cyclase activity was sharply increased in comparison with that in hyperplastic adrenals. In the majority of malignant tumours the adenylate cyclase response to ACTH was either altogether absent or sharply decreased. In benign adrenal tumours the basal activity of the enzyme was unchanged and the enzyme response to ACTH was essentially normal. The decrease of adenylate cyclase response to ACTH in malignant tumours is apparently not due to the impaired catalytic activity of the enzyme, since its response to stimulation by sodium fluoride remains unaffected. In some tumours (one malignant and two benign ones) a non-specific stimulation of adenylate cyclase by hormones, which are not natural activators of the enzyme was observed. It was assumed that these changes are due to the damage of hormonal receptors in adrenal tumours. PMID- 6264972 TI - [Changes in some properties of 3':5'-AMP-dependent protein kinase from rat skeletal muscles during physical exercise]. AB - During 6-week training of rats the activity of isoenzymes I and II of soluble 3':5'-AMP-dependent protein kinase increases by 22 and 33%, respectively. A long term physical load does not cause any significant changes in the activity of both isoenzymes. The maximal activity of the isoenzymes from skeletal muscles of the control and experimental rats is observed at the same concentrations of 3':5'-AMP and pH of 6,0-6,5. During training and under physical load the apparent Km values for ATP of both isoenzymes of 3':5'-AMP-dependent protein kinase do not change significantly, whereas that of V shows an increase. The apparent Km and V values for the histone increase for isoenzyme I obtained from skeletal muscles of trained rats both at rest and under physical load. In case of isoenzyme II the Km value for the histone decreases, while that of V remains unchanged. The changes in the properties of isoenzymes I and II of 3':5'-AMP-dependent protein kinase from skeletal muscles suggest the participation of the enzyme in adaptation to systematic muscular activity. PMID- 6264974 TI - [Effect of digitonin on the activity of Na,K-ATPase from bovine brain]. AB - The kinetic properties of intact and digitonin-treated Na,K-ATPase from bovine brain were studied. The temperature dependence curve for the rate of ATP hydrolysis under optimal conditions (upsilon 0) in the Arrhenius plots shows a break at 19-20 degrees. The temperature dependence curves for Km' and Km" have breaks at the same temperatures, while the Arrhenius plot for V is linear. The value of the Hill coefficient (nH) for ATP at 37 degrees is variable depending on ATP concentration, i. e. it is less than 1 at ATP concentrations below 50 mkM and is increased up to 3.2 at higher concentrations of the substrate. At high ATP concentrations the value of nH depends on temperature, falling down to 2.1 at 23 degrees and then down to 1 within the temperature range of 21-19 degrees. A further decrease in temperature does not significantly affect the nH value. Digitonin irreversibly inhibits Na, K-ATPase. ATP hydrolysis is more sensitive to the effect of the detergent than is nNPP hydrolysis, i. e. after complete inhibition of the ATPase about 40% of the phosphatase activity are retained. Treatment of Na,K-ATPase by digitonin results in elimination of the breaks in the Arrhenius plots for upsilon 0, Km' and Km", whereas the temperature dependence plot of V remains linear. Simultaneously digitonin eliminates the positive cooperativity of the enzyme for ATP. It is assumed that Na, K-ATPase from bovine brain is an oligomer of the (alpha beta) 4 type. Digitonin changes the type of interaction between the protomers within the oligomeric complex by changing the lipid environment of the enzyme or the type of protein -- lipid interactions. PMID- 6264975 TI - [Generation of superoxide anion radicals and hydrogen peroxide in the auto oxidation of caffeic acid]. AB - Caffeic acid (5-200 mkM) reduces cytochrome c during autoxidation in potassium phosphate buffer, pH 7-8. The reduction is inhibited by superoxide dismutase, which suggests generation of superoxide anion radicals. The generation rate is 0.028-0.115 mkmoles O2- per min. Superoxide appears to be a side product of the reaction, since the autoxidation of caffeic acid itself (followed by A420) is not inhibited by superoxide dismutase. The autoxidation is accompanied by oxygen of consumption. An addition of catalase results in liberation of some part of consumed oxygen, this being indicative of accumulation of hydrogen peroxide. Caffeic acid is known to be responsible for the resistance of plants to parasites because of its toxicity. This function presumably depends on superoxide or other reactive oxygen species. PMID- 6264976 TI - [Interaction of Na,K-ATPase with modifying ATP analogs and chloromethylphosphonic acid]. AB - The interaction of synthetic ATP analogs, containing active groups in the triphosphate moiety and in the 8-position of the nucleotide molecule, with highly purified Na, K-ATPase from the medullar layer of porcine kidney was studied. It was found that 11 out of 17 ATP analogs studied irreversibly inhibit the ATPase activity of the enzyme. The pH optimum of the enzyme inactivation by adenosine-5' (beta-chloroethylphosphate) and adenosine-5'-(p-fluorosulfonylphenylphosphate) beside the pronounced protective effect of ATP suggests possible covalent blocking of histidine and dicarboxylic amino acid residues in the enzyme active center. The irreversible inhibition of the enzyme by "oxo-ATP" containing aldehyde groups in the modified ribose residue in the presence of sodium borohydride suggests a possible presence of the lysine residue epsilon-amino group in the ATP binding site of the enzyme. Na, K-ATPase was found to possess an inorganic phosphate binding site, which is specifically blocked by chloromethylphosphonic acid. the accessibility of this site for modification depends on ATP, NA+ and K+. PMID- 6264977 TI - [Interaction between cyclic adenosine-3':5'-monophosphate phosphodiesterase and structural analogs of the substrate]. AB - The interaction between synthetic structural analogs of cyclic adenosine-3':5' monophosphate (3':5'-AMP) and rat liver 3':5'-AMP phosphodiesterase was studied. Various groups, including those capable of covalent binding to the protein, were injected into certain sites of the 3':5'-AMP molecule. All the compounds tested exerted an inhibiting effect; in seven cases this effect was irreversible. Some peculiarities of 3':5'-AMP binding in the enzyme active center are discussed. PMID- 6264979 TI - [Serotonin and D-lysergic acid diethylamide receptors in the mammalian brain]. PMID- 6264978 TI - [Methylation of eukaryote DNA. II. Biological significance]. PMID- 6264980 TI - Plasma catecholamines and pituitary adrenal hormones related to mental task demand under quiet and noise conditions. AB - Plasma levels of catecholamines and pituitary adrenal hormones were measured in 20 min samples from eight subjects, in one control session and two experimental sessions, while they performed a short-term memory task under quiet of noise conditions. Performing the task led to significant increase in the plasma levels of cortisol, adrenaline and noradrenaline, whereas no variations in growth hormone and dopamine were observed. Similarly, significant changes occurred in urinary catecholamine excretion. A significant correlation was found between individual plasma cortisol increments and error-rates assessed from an accuracy of recall variable. For adrenaline and noradrenaline, an early response apparently linked with an anticipatory process preceded the task. Exposure to noise did slightly amplify cortisol response to the task, but during the first experimental session, with or without noise, the task elicited greater cortisol increases in all subjects than during the second session. These results provide evidence for a relationship between sympathoadrenocortical activity and attentional demand, whereas cortisol increments seem to be more specifically related to better coping with the task. Frequent hormone level measurements during a prolonged mental task might clarify the complex relationship between time-related bodily hormonal changes, performance and subjective feelings. PMID- 6264982 TI - Binding of dihydroalprenolol and dihydroergocryptine to sheep myometrium. PMID- 6264981 TI - Direct effects of gonadotropin releasing hormone and its antagonist upon ovarian functions stimulated by FSH, prolactin, ans LH. PMID- 6264983 TI - Coupling of beta-adrenoreceptors in rat uterine smooth muscle. PMID- 6264984 TI - Relative importance of the adenohypophyseal and gonadal sites in inhibitory action of LHRH agonists. PMID- 6264985 TI - A simulated study of historical controls using real data. AB - Data from the first and second National Wilms' Tumor study were used to simulate how use of the first study's historical controls in the design and analysis of the second study might have influenced the conclusions of the investigations. It was seen that the conclusions from a fully-randomized study can differ in substances from one using historical controls. PMID- 6264986 TI - The structure of a DNA unwinding protein and its complexes with oligodeoxynucleotides by x-ray diffraction. AB - The structure of the gene 5 DNA unwinding protein from bacteriophage fd has been solved to 2.3 A resolution by x-ray diffraction techniques. The molecule contains an extensive cleft region that we have identified as the DNA binding site on the basis of the residues that comprise its surface. The interior of the groove has a rather large number of basic amino acid residues that serve to draw the polynucleotide backbone into the cleft. Arrayed along the external edges of the groove are a number of aromatic amino acid side groups that are in position to stack upon the bases of the DNA and fix it in place. The cleft then acts as an elongated pair of jaws that draws the DNA between them by charge interactions involving the phosphates with the interior lysines and arginines. The jaws then close on the DNA strand through small conformation changes and the rotation of aromatic side-chains into position to stack upon the purines and pyrimidines. Complexes of the gene 5 protein with a variety of oligodeoxynucleotides have been formed and crystallized for x-ray diffraction analysis. The crystallographic parameters of four different unit cells indicate that the fundamental unit of the complex is composed of six gene 5 protein dimers. We believe this aggregate has 622 point group symmetry and is a ring formed by end to end closure of a linear array of six dimers. From our results we have proposed a double helical model for the gene 5 protein-DNA complex in which the protein forms a spindle or core around which the DNA is spooled. 5.0-A x-ray diffraction data from one of the crystalline complexes is currently being analyzed by molecular replacement techniques to obtain what we believe will be the first direct visualization of a protein-deoxyribonucleic acid complex approaching atomic resolution. PMID- 6264987 TI - Nucleosome structure and conformational changes. AB - We have used a variety of chemical probes to measure the accessibility of DNA on the surface of the nucleosome. We review these results, and describe new experiments which show that T4 phage DNA can form complexes with the core histones, possessing the properties of normal nucleosomes. Since T4 DNA is largely occupied by glucose residues in the major groove, this suggests (as did earlier probe experiments) that the major groove is not filled with histone amino acid side chains. We also report results of recent measurements which appear to show that only a few strong charge interactions are involved in the attachment of the terminal 20 nucleotide pairs at each end of nucleosome core DNA. We speculate on the possible functional significance of the accessibility of DNA revealed by all of these experiments. We have also examined conformational changes induced in nucleosomes at high ionic strength (0.5-0.7M NaCl). The frictional coefficient is found to undergo a small increase in this region, not consistent with models in which the nucleosome is completely unfolded, but possibly reflecting the dissociation of terminal DNA from the nucleosome surface. PMID- 6264988 TI - On the thermodynamics and kinetics of the cooperative binding of bacteriophage T4 coded gene 32 (helix destabilizing) protein to nucleic acid lattices. AB - In this paper we summarize a series of thermodynamic, and preliminary kinetic, studies on the molecular details and specificity of interaction of phage T4-coded gene 32-protein (GP32) with nucleic acid lattices. It is shown that the binding of GP32 to short (l = 2--8 residues) oligonucleotides is essentially independent of base composition and sugar-type, as well as of salt concentration. In contrast, cooperative (continuous) or isolated binding of GP32 to single-stranded polynucleotides is base and sugar composition-dependent (binding is tighter to DNA than to RNA) and highly dependent on salt concentrations. Binding constants (K), cooperativity parameters (w), and binding site sizes (n) are determined for binding to various nucleic acid lattices under a variety of environmental conditions. These results are used to show that GP32 can bind to nucleic acid lattices in two different conformations, and to characterize the molecular details of these binding species. Further insight into the molecular origins of binding cooperativity is obtained by determining these thermodynamic parameters also for the specifically proteolytically degraded GP32 fragments GP32 I (C terminal peptide removed) and GP32 III (C- and N-terminal peptides removed). It is also shown that these GP32-nucleic acid binding measurements can be used to provide a quantitative molecular interpretation of the sequential (competitive) binding equilibria involved in the autogenous translational regulation of GP32 synthesis (Lemaire et al., 1978, J. Mol. Biol. 126:73, 1978), and to illustrate some general principles of the development of interactional specificity in cooperatively binding protein-nucleic acid complexes. Preliminary experiments have also been carried out on the kinetics of GP32 association to, and dissociation from, single-stranded nucleic acid lattices. In particular, fluorescence stopped-flow measurements of the dissociation of GP32 from such lattices as a function of lattice saturation (and protein cluster size) can be interpreted to suggest that the protein may translocate ("slide") on the lattice before dissociation, These studies permit an approach to possible rates and mechanisms of such translocation events. PMID- 6264989 TI - Interactions of solvent with the heme region of methemoglobin and fluoro methemoglobin. AB - It is now more than 20 years since Davidson and collaborators (1957, Biochim. Biophys, Acta. 26:370-373; J. Mol. Biol. 1:190-191) applied the theoretical ideas of Bloembergen et al. (1948. Phys. Rev. 73:679-712) on outer sphere magnetic relaxation of solvent protons to studies of solutions of methemoglobin. From then on, there has been debate regarding the relative contributions to paramagnetic solvent proton relaxation by inner sphere (ligand-exchange) effects and by outer sphere (diffusional) effects in methemoglobin solutions. Gupta and Mildvan (1975. J. Biol. Chem 250:146-253) extended the early measurements, attributed the relatively small paramagnetic effects to exchange with solvent of the water ligand of the heme-Fe3+ ion, and interpreted their data to indicate cooperativity and an alkaline Bohr effect in the presence of inositol hexaphosphate. They neglected the earlier discussions entirely, and made no reference to outer sphere effects. We have measured the relaxation rate of solvent protons as a function of magnetic field for solutions of methemoglobin, under a variety of conditions of pH and temperature, and have given careful consideration to the relatively large diamagnetic corrections that are necessary by making analogous measurements on oxyhemoglobin, carbonmonoxyhemoglobin, and cyano- and azide-methemoglobin. (The latter two, because of their short electronic relaxation times, behave as though diamagnetic). We show that the paramagnetic contribution to solvent relaxation can be dominated by outer sphere effects, a result implying that many conclusions, including those of Gupta and Mildvan, require reexamination. Finally, we present data for fluoro-methemoglobin, which relaxes solvent protons an order of magnitude better than does methemoglobin. Here one has a startling breakdown of the dogma that has been the basis for interpreting many ligand replacement studies; in contrast to the prevailing view that replacement of a water ligand of a protein-bound paramagnetic ion by another ligand should decrease relaxation rates, replacement of H2O by F- increases the relaxation rate drastically. The data can all be reconciled, however, with what is anticipated from knowledge of ligand interactions in the heme region. PMID- 6264991 TI - [Changes in spatial organization in sarcoplasmic reticulum membranes in rabbits with experimental thyrotoxicosis]. AB - The structure of sarcoplasmic reticulum membranes (SR) of skeletal muscles from normal and thyrotoxic rabbits was studied with the use of the fluorescent probe pyrene. It was found that protein globules in SR preparations of thyrotoxic animals were submerged into the lipid bilayer to a greater extent than in the reticulum of normal animals. Electrophoresis in polyacrylamide gel revealed no detectable differences between SR of normal and thyrotoxic rabbits. The ratio protein/lipid in SR membranes remained 2:1 in rabbits with thyrotoxicosis. PMID- 6264992 TI - [Compatibility between F-like genetic transfer factors]. AB - A study has been made of compatibility among four F-like factors of genetic transfer (pAP22-4, pAP38, pAP39 and pAP41) labeled separately by transpozones Tn1 and Tn9. It has been established that pAP38 transfer factor is compatible with plasmids pAP22-4, pAP39 and pAP412, while pAP41 transfer factor is compatible with plasmids pAP22-4 and pAP38 but is incompatible with plasmid pAP39. PMID- 6264990 TI - Structural features and the reaction mechanism of cytochrome oxidase: iron and copper X-ray absorption fine structure. AB - X-ray edge absorption of copper and extended fine structure studies of both copper and iron centers have been made of cytochrome oxidase from beef heart, Paracoccus dentrificans, and HB-8 thermophilic bacteria (1-2.5 mM in heme). The desired redox state (fully oxidized, reduced CO, mixed valence formate and CO) in the x-ray beam was controlled by low temperature (-140 degrees C) and was continuously monitored by simultaneous optical spectroscopy and by electron paramagnetic resonance (EPR) monitoring every 30 min of x-ray exposure. The structure of the active site, a cytochrome a3-copper pair in fully oxidized and in mixed valence formate states where they are spin coupled, contains a sulphur bridge with three ligands 2.60 +/- 0.03 A from Fea3 and 2.18 +/- 0.03 A from Cua3. The distance between Fea3 and Cua3 is 3.75 +/- 0.05 A, making the sulphur bond angle 103 degrees reasonable for sp3 sulphur bonding. The Fea3 first shell has four typical heme nitrogens (2.01 +/- 0.03 A) with a proximal nitrogen at 2.14 +/- 0.03 A. The sixth ligand is the bridging sulphur. The Cua3 first shell is identical to oxidized stellacyanin containing two nitrogens and a bridging sulphur. Upon reduction with CO, the active site is identical to reduced stellacyanin for the Cua3 first shell and contains the sulphur that forms the bridge in fully oxidized and mixed valence formate states. The Fea3 first shell is identical to oxyhemoglobin but has CO instead of O2. The other redox centers, Fea and the other "EPR detectable" Cu are not observed in higher shells of Fea3. Fea has six equidistant nitrogens and Cua has one (or two) nitrogens and three (or two) sulphurs with typical distances; these ligands change only slight on reduction. These structures afford the basis for an oxygen reduction mechanism involving oxy- and peroxy intermediates. PMID- 6264993 TI - Megakaryoblastic leukemia presenting as acute myelofibrosis -- a study of four cases with the platelet-peroxidase reaction. AB - Acute myelofibrosis (AM) or malignant myelosclerosis is a myeloprofilerative syndrome in which bone marrow fibrosis is associated with a proliferation of immature myeloid cells. In four patients with typical AM, investigated by the platelet-peroxidase reaction at ultrastructural level, the blast cells were found to be megakaryoblasts. One patient, treated with the drug combination DAT, achieved a complete remission of 5 mo duration. This study supports the view that megakaryoblastic leukemia is the most frequent underlying cause of AM and proposes that it should be classified as a form of acute myeloid leukemia. PMID- 6264994 TI - The in vitro effects of Newcastle disease virus on the metabolic and antibacterial functions of human neutrophils. AB - Live Newcastle disease virus (NDV) was used to investigate the in vitro effects of a viral infection on phagocytosis, chemiluminescence generation, superoxide production, oxygen consumption, NADPH-oxidase activity, and intracellular killing of bacteria by Ficoll-Hypaque separated human neutrophils. Phagocytosis of oil red O particles by NDV-treated PMN was inhibited by 50%. Chemiluminescence by PMN was inhibited 79% after zymosan stimulation and 86% after tetradeconyl phorbol acetate stimulation. Superoxide generation was inhibited by 68%. Oxygen consumption was inhibited in the presence of NDV by 37% after stimulation with phorbol myristate acetate, while membrane-associated NADPH-enzyme activity was decreased by 19%. The percent of surviving intracellular S. aureus was significantly elevated in NDV-treated PMN after 60 and 120 min of incubation. Purified bacterial neuraminidase markedly suppressed chemiluminescence, while neuraminic acid blocked the effects of the virus. These observations suggest that infections with myxoviruses may suppress a number of vital neutrophil functions. It appears that the effects may be partly mediated by the interaction of viral neuraminidase with the external neutrophil membrane. PMID- 6264995 TI - Phagocytosis-induced modulation of human neutrophil chemotaxis receptors. PMID- 6264997 TI - Lymphoblast purine pathway enzymes in B-cell acute lymphoblastic leukemia. AB - Activities of enzymes of the purine metabolic pathway, adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and 5'-nucleotidase (5'-N), were investigated in the lymphoblasts of a patient with B-cell acute lymphoblastic leukemia. These lymphoblasts exhibited increased ADA activity and diminished activities of both PNP and 5'N' as compared to normal lymphocytes as well as non T, non-B leukemia cells. This enzymatic pattern is identical to that which has been described in T-cell leukemic lymphoblasts and differs from that which has been observed in the malignant cells of undifferentiated B-cell lymphomas. These data suggest that there is biochemical heterogeneity within the spectrum of B cell malignancies. Furthermore, inhibitors of ADA may be of use in those B-cell lymphoid neoplasms that exhibit increased ADA activity. PMID- 6264996 TI - Monocyte-mediated antibody-dependent cell-mediated cytotoxicity: the role of the metabolic burst. AB - Human monocytes respond to opsonized microorganisms with a "metabolic burst" composed of an increase in oxygen consumption, an increase in hexose monophosphate shunt (HMPS) activity, and the generation of reactive oxygen species (ROS). We investigated the role of the metabolic burst in antibody dependent cell-mediated cytotoxicity (ADCC) by human monocytes toward anti-D coated erythrocyte target cells because recent studies suggested a role for oxygen-dependent bactericidal mechanisms in ADCC. In normal monocytes, we found that ADCC was nearly halved under hypoxic conditions. Several agents known to impair activation of the burst, such as vincristine, cation chelators, and a sulfhydryl reagent, all decreased cytotoxicity if added before initiation of contact between target and effector cells. Cytotoxicity was inhibited by 2 deoxyglucose but not fluoride, suggesting a nonglycolytic role for glucose in ADCC, perhaps in the HMPS pathway. Although these data suggested a role for the metabolic burst in ADCC, scavengers of ROS did not impair cytotoxicity, and monocytes from chronic granulomatous disease (CGD) patients who had a defective metabolic burst had normal levels of ADCC. We conclude that ADCC toward anti-D coated erythrocyte target cells was the result of at least two independent but closely related cytotoxic pathways. Although one of these pathways appeared to involve the metabolic burst, the potentially cytotoxic reactive oxygen species did not appear to play a role in this system. PMID- 6264998 TI - Effects of platelet inhibitors on the platelet aggregation induced by plasma from patients with thrombotic thrombocytopenic purpura. AB - Antiplatelet drugs have been used in the treatment of thrombotic thrombocytopenic purpura (TTP) but there in vivo efficacy remains controversial. It has been shown that, in vitro, the plasmas obtained from patients with TTP induced the aggregation of washed platelets from normal donors as well as patients in remission. The effects of platelet inhibitors on the TTP plasma-induced platelet aggregation were examined. It was found that aspirin, indomethacin, ibuprofen, sulfinpyrazone, 5, 8, 11, 14-eisacotetraynoic acid, prostaglandin E1, prostaglandin I2, dBcAMP, apyrase, creatine phosphate/creatine phosphokinase, antimycin, 2-deoxy-D-glucose, dipyridamole, clofibrate, dextran 40, dextran 70, dibucaine, xylocaine, methylmaleimide, and ethylenediamine tetraacetic acid had little or no effect at all. These data lead us to conclude that at least in certain cases, antiplatelet drugs probably play a limited role in the treatment of patients with TTP. PMID- 6264999 TI - Accidental poisoning of ruminants with the fertilizer, urea in Ibadan, Nigeria. PMID- 6265000 TI - [The angiotensin I converting enzyme (author's transl)]. PMID- 6265001 TI - Adaptation to oxygen by preexposure to hypoxia: enhanced activity of manganese superoxide dismutase. PMID- 6265002 TI - NADPH-dependent oxygen reductase activity in pulmonary macrophages. PMID- 6265003 TI - A dual effect of L-1-tosylamide-2-phenylethyl chloromethyl ketone on the respiratory metabolism of guinea pig phagocytes. PMID- 6265004 TI - Early formation of hydroxyl-like radical in particulate fraction from human neutrophils. PMID- 6265005 TI - The biological effects of the superoxide radical and its products. PMID- 6265006 TI - Superoxide anion: its involvement in carbon disulfide hepatotoxicity in phenobarbital-treated rats. PMID- 6265007 TI - The pathogenic role of superoxide radicals in inflammation: efficacy of exogenous superoxide dismutase. PMID- 6265008 TI - Involvement of singlet oxygen in biochemical systems. PMID- 6265009 TI - Radical chemistry of alloxan-dialuric acid: role of the superoxide radical. PMID- 6265010 TI - Formation and detection of superoxide ions in biological systems. Their involvement in the production of more reactive radicals. PMID- 6265011 TI - Superoxide dismutation by low molecular weight Cu-complexes. PMID- 6265012 TI - Inactivation of human CuZn superoxide dismutase during exposure to superoxide radical and hydrogen peroxide. PMID- 6265013 TI - [Discovery and study of Tn951, the first lactose transposon]. PMID- 6265014 TI - [Microbial flora of beef extract imported from Australia, Uruguay, Italy and Brazil (author's transl)]. PMID- 6265015 TI - alpha 1-adrenoceptors can mediate chronotropic responses in the rat heart. AB - In the pithed rat, amidephrine a "selective" alpha 1-adrenoceptor agonist, evokes a positive chronotropic response. This response can be antagonized by prazosin but not by propranolol or by rauwolscine. Similarly, part of the chronotropic response to cardioaccelerator nerve stimulation is resistant to blockade by propranolol but is sensitive to prazosin or WB4101. We conclude that alpha 1 adrenoceptors can mediate a chronotropic response in the rat heart either to exogenous agonists or to the endogenous neurotransmitter noradrenaline. PMID- 6265016 TI - The effect of heavy metal chelators on the renal accumulation of platinum after cis-dichlorodiammineplatinum II administration to the rat. AB - 1 Rats received a total of 18 mg/kg cis-dichlorodiammineplatinum (II) (CDDP) intravenously and were treated concomitantly with calcium-disodium ethylenediaminetetraacetic acid (CaNa2EDTA), 2,3-dimercaptopropanol (BAL), deferoxamine, 2,3-dimercaptosuccinic acid (DMS) or vehicle. In comparison to controls, renal platinum concentration was significantly reduced in the DMS and deferoxamine-treated groups. However, significant deterioration occurred in the deferoxamine-treated group. The hepatic platinum concentration was unaffected by the chelating agents. 2 Following a dose of 6 mg/kg CDDP intravenously, eight days of treatment with DMS, 50 mg/kg daily, had no effect on renal platinum excretion, while treatment with 100 or 200 mg/kg daily reduced renal platinum concentration by 50%. 3 In order to determine whether DMS could prevent the nephrotoxicity of CDDP, rats were given 6 mg/kg CDDP intravenously, followed by a four day course of DMS treatment at doses of 0, 50, 100 or 200 mg/kg daily begun 3 h after the CDDP dose. DMS failed to prevent renal toxicity as indicated by weight loss, serum creatinine concentration, renal histology, and the urinary excretion of N-acetyl-beta-glucosaminidase, a renal tubular enzyme. PMID- 6265017 TI - The effect of anaesthetics on the uptake and release of gamma-aminobutyrate and D aspartate in rat brain slices. AB - 1 The effect of various concentrations of thiopentone, pentobarbitone, methohexitone, hydroxydione, alphaxalone/alphadolone, ketamine, alpha-chloralose, and urethane on the transport of radiolabelled gamma-aminobutyric acid (GABA) and D-aspartate was investigated. 2 Uptake of the amino acids was weakly inhibited, if at all, by the anaesthetics and it is unlikely that such effects contribute significantly to their physiological function. 3 The spontaneous efflux of GABA and D-aspartate was not detectably altered by any of the drugs tested. 4 Thiopentone, pentobarbitone, methohexitone and hydroxydione inhibited K+ stimulated GABA and D-aspartate release. The other anaesthetics had no effect on K+-stimulated amino acid release. 5 The rank order of potency of the inhibitors of K+-stimulated amino acid release did not correlate with their anaesthetic potency. Furthermore not all inhibitors appeared to be very effective at anaesthetic concentrations. 6 It is concluded that although it is possible that inhibition of excitatory transmitter release may be involved in the anaesthetic action of some anaesthetics, for many of the substances tested in this study such as mechanism does not appear to be implicated. PMID- 6265018 TI - Separate 5-hydroxytryptamine receptors on the salivary gland of the blowfly are linked to the generation of either cyclic adenosine 3',5'-monophosphate or calcium signals. AB - 1 5'-Hydroxytryptamine (5-HT) stimulates the formation of two separate second messengers in the salivary gland of the blowfly. Activation of adenylate cyclase raises adenosine 3',5'-monophosphate (cyclic AMP) whereas the hydrolysis of phosphatidylinositol (PI) is associated with an increase in calcium permeability. The possibility that these two signal pathways might be controlled by separate 5 HT receptors was studied by testing the specificity of 5-HT analogues and antagonists. 2 The parent compound 5-HT was found to stimulate both cyclic AMP formation and the related parameters of PI hydrolysis and calcium transport with similar dose-response relationships. 3 Certain analogues such as 4- and 5-fluoro alpha-methyltryptamine were capable of raising cyclic AMP levels and stimulating fluid secretion but did not stimulate the hydrolysis of PI or the entry of calcium. 4 Other analogues, which had chloro or methyl substituents at the 5 position, were found to stimulate the hydrolysis of PI and the transport of calcium at much lower doses than those required to stimulate the formation of cyclic AMP. 5 Antagonists were also found to exert selective effects. Methysergide was a potent inhibitor of PI hydrolysis whereas cinanserin was far more selective in blocking the stimulatory effect of 5-HT on cyclic AMP formation. 6 It is concluded that 5-HT acts on two separate receptors, a 5-HT1 receptor acting through calcium and a 5-HT2 receptor which mediates its effects through cyclic AMP. PMID- 6265020 TI - Effects of divalent cations on responses of a sympathetic ganglion to 5 hydroxytryptamine and 1,1-dimethyl-4-phenyl piperazinium. AB - 1 The effects of raising or lowering [Ca(2+)](o) or [Mg(2+)](o) on potential changes evoked by 5-hydroxytryptamine (5-HT) and by the nicotinic agonist, 1,1 dimethyl-4-phenyl piperazinium (DMPP) have been investigated.2 Changes in membrane potential were measured at the ganglion or in postganglionic axons by the sucrose-gap technique. The ganglionic response to both 5-HT and DMPP was a depolarization followed by an after-hyperpolarization (AH). AH decayed exponentially over most of its time course; the time constant of decay for 5-HT responses was 4.4 +/- 0.3 min (mean +/- s.e.mean, rate constant 0.23 min(-1)) and that for DMPP responses was not significantly different, being 3.9 +/- 0.3 min (rate constant 0.26 min(-1)).3 Increasing [Ca(2+)](o) to 5.1 or 7.6 mM caused some hyperpolarization of the ganglion, reduced the amplitude of depolarizations evoked by 5-HT by 29% and usually potentiated responses to DMPP (average 12%). Ca free solutions caused a depolarization of the ganglion, increased the amplitude of depolarizations evoked by 5-HT by 23% and reduced that of depolarizations to DMPP by 32%. [Mg(2+)](o) 12.7 and 25.4 mM caused depolarizations of the ganglion and reduced the amplitude of depolarizations evoked by 5-HT by 34 and 84%, respectively, and those to DMPP by 10 and 75%, respectively. Mg-free solutions or low [Mg(2+)](o) caused a slow depolarization of the ganglion and reduced the amplitude of depolarizations to both 5-HT and DMPP by approx. 20%. Ca/Mg-free solutions produced a slow depolarization of the ganglion, increased the amplitude of depolarizations evoked by 5-HT by 78% and reduced those to DMPP by 58%.4 Increasing [Ca(2+)](o) reduced the amplitude of AH evoked by 5-HT by 50% and increased that to DMPP by 73%, while prolonging AH duration and increasing the time constant of decay. Ca-free solutions had complex effects on AH evoked by 5 HT, which were increased on average by 116%, and depressed AH evoked by DMPP; in both cases there was a decrease in the time constant of decay. [Mg(2+)](o) 12.7 mM reduced the amplitude of AH evoked by 5-HT more than that evoked by DMPP, and increased the rate of decline of the exponential phase. Low Mg solutions reduced in amplitude the AH evoked by 5-HT by 56% and the AH evoked by DMPP by 38%. The time constant of decay was increased. Ca/Mg-free solutions reduced AH amplitude in both 5-HT and DMPP responses. The effects on time constant are consistent with the generation of AH by an electrogenic sodium pump, the ATP-ase of which is Mg(2+)-dependent and inhibited by Ca(2+).5 Responses to 5-HT could be recorded from postganglionic axons and consisted of a rapid depolarization, sometimes followed by an AH whose time constant of decay was smaller than that of ganglionic responses. Full dose-response curves in control and test media could be obtained. In Ca/Mg-free solutions, 5-HT depolarizations were potentiated but no significant shift in the curve was observed.6 It is suggested that divalent cations modulate the coupling between 5-HT receptor and ion channel, an increase in [Ca(2+)](o) reducing the coupling or stabilizing the ion channel in the closed conformation. Ca(2+) and Mg(2+) may compete for the same binding site. This mechanism does not appear to be involved at nicotinic receptors and their related ion channels. PMID- 6265019 TI - Distinction between the effects of barbiturates, benzodiazepines and phenytoin on responses to gamma-aminobutyric acid receptor activation and antagonism by bicuculline and picrotoxin. AB - 1 Interactions of depressant and anticonvulsant drugs with the neuronal gamma aminobutyric acid (GABA) receptor + effector system have been examined on afferent fibres to the rat cuneate nucleus in vitro. Three types of interaction have been measured: (a) potentiation of depolarizing responses to the GABA analogue, muscimol: (b) reduction in the potency of bicuculline as an antagonist of muscimol at the GABA receptor: (c) reduction in the potency of picrotoxin as an antagonist of muscimol acting on the effector mechanism. 2 Phenobarbitone reduced the potency of picrotoxin in doses which did not affect the potency of bicuculline and which caused only a small potentiation of muscimol. Pentobarbitone did not show such selectivity, a reduction in potency of picrotoxin always being accompanied by a reduction in potency of bicuculline and a substantial potentiation of muscimol. 3 Flurazepam and lorazepam both reduced the potency of picrotoxin without affecting that of bicuculline and with very little potentiation of muscimol. Phenytoin had no effect on the potency of picrotoxin whilst potentiating muscimol to the same extent as phenobarbitone. 4 The spectrum of drug activity in reducing the potency of picrotoxin correlates well with the reported anticonvulsant effects of these drugs against kindled amygdaloid seizures. Potentiation of muscimol and reduction of bicuculline potency appear more closely related to hypnotic properties. PMID- 6265021 TI - The surgical treatment of enteritis necroticans. AB - The optimum timing of surgery in acute cases of enteritis necroticans with bowel obstruction has not been established. Two similar groups of patients with this condition were sequentially compared to determine if early surgical intervention reduces mortality. In the first group 42 per cent of the 79 patients received medical treatment only and 58 per cent had an operation at a median time of 4 days following the onset of obstruction. In the second group 96 per cent of the 50 patients received surgery at a median time of 2 days following the onset of obstruction and 4 per cent received medical treatment only. The mortality in the second group (21 per cent) was half that of the first group (43 per cent). Surgery after a short period of resuscitation is advocated for all cases of enteritis necroticans with bowel obstruction. PMID- 6265023 TI - Coincident cytomegalovirus infection and toxoplasmosis in an uncompromised host. PMID- 6265022 TI - Radioligand binding studies of adrenergic receptors and their clinical relevance. PMID- 6265024 TI - The 1975 foot-and-mouth disease epidemic in Malta. I: Experimental studies with the causal virus strain O1 Malta. PMID- 6265025 TI - GABA and muscimol open ion channels of different lifetimes on cultured mouse spinal cord cells. AB - Intracellular recordings of cultured mouse spinal neurons were used to examine the effects of gamma-aminobutyric acid (GABA) and the GABA analog muscimol on neuronal excitability. Muscimol was about twice as effective as GABA in increasing membrane conductance to C1-ions. Fluctuation analysis of membrane current responses showed that muscimol activated ion channels with the same conductance as GABA but with about the average duration. The results provide an economical explanation for the greater potency of muscimol in depressing excitability. PMID- 6265026 TI - Norepinephrine depletion alters cerebral oxidative metabolism in the "active" state. AB - Unilateral chemical lesion of the nucleus locus coeruleus in rats produced unilateral depletion of ipsilateral cortical norepinephrine. Norepinephrine depletion was not associated with changes in "resting" metabolic balance of the cerebral cortex, as determined by in situ reflection spectrophotometry of the redox state of cytochrome oxidase. Norepinephrine depletion, however, caused slowing of the transient metabolic response to sudden increases in energy demand produced by direct cortical electrical stimulation. The effect was apparent in the redox state of both cytochrome oxidase and NAD, the latter being measured, also in situ, by reflection microfluorometry. These results demonstrate that norepinephrine has a role in modulating the response to increased metabolic demand in the cerebral cortex. Norepinephrine may mediate its effect by potentiating Na+, K+-ATPase or through its effects on vascular reactivity, or both. PMID- 6265028 TI - 8-Br-cyclic GMP mimics activation of muscarinic autoreceptor and inhibits acetylcholine release from rat hippocampal slices. PMID- 6265027 TI - Nitrous oxide alters oxidative metabolic activities of rat neocortex in situ. AB - Nitrous oxide was shown by dual wavelength reflection spectrophotometry to decrease the ratio of reduction/oxidation of cytochrome a,a3 and to increase local blood volume in the cerebral cortex of rats in situ. These changes were in contrast to the decreased local blood volume and increased reduction of cytochrome a,a3 produced by pentobarbital. These effects of nitrous oxide were similar to those produced by respiration of 95% O2 with 5% CO2 except that such inspiration resulted in hemoglobin oxygenation while N2O produced some disoxygenation of hemoglobin. We conclude that the N2O effect on metabolism is likely due to increased energy demand. These results also provide some indication that changes in oxidative functioning in brain tissues may occur without alteration in the concentrations of high energy phosphate compounds. PMID- 6265029 TI - Potassium stimulated 45Ca uptake by cortical slices of rat brain: effects of cyclic nucleotide derivatives. AB - The effects of dibutyryl cyclic GMP (db-cGMP) and dibutyryl cyclic AMP (db-cAMP) on potassium-stimulated 45Ca uptake by cortical slices of rat brain were investigated. db-cGMP specifically inhibited the initial rate of potassium stimulated 45Ca uptake in a dose-dependent manner. Our findings supported the suggestion that cyclic GMP may play a regulatory role in depolarization-elicited Ca2+ influx in nerve endings in situ. PMID- 6265030 TI - Increased ouabain binding after repeated noradrenergic stimulation. AB - Acute noradrenergic stimulation has previously been shown to stimulate brain (Na+, K+)-adenosine triphosphatase activity. Effects of repeated stimulation with piperoxane were examined in the present study. Daily piperoxane increased ouabain binding, measured 24 h after the last dose, after 4 days or 3 weeks treatment; K+ p-nitrophenylphosphatase was increased after 3 weeks. Prazosin, which, like piperoxane, activates presynaptic noradrenergic neurons but, unlike piperoxane, blocks postsynaptic receptors, did not increase K+-p-nitrophenylphosphatase, and decreased ouabain binding after 3 weeks. PMID- 6265031 TI - Evidence of facilitatory coerulospinal action in lumbar motoneurons of cats. AB - Functional connectivity of the feline coerulospinal projection was delineated by utilizing the combined approaches of antidromic activation and electrical stimulation. We isolated 25 locus coeruleus (LC) neurons that were electrophysiologically identified and histologically verified and that could be driven by stimulating the spinal cord. Antidromicity of the spike potentials was confirmed by the constant latency, the high frequency (100 Hz) following, fractionation of the initial segment-somatodendritic potential, and collision between the antidromic and the spontaneous orthodromic spikes. The mean conduction speed was 20 +/- 8 m/sec (range = 7 to 32 m/sec). Intracellular studies revealed facilitatory LC actions in 22 lumbar motoneurons (MNs), In 13 MNs, LC activation alone produced slow-rising excitatory postsynaptic potentials (EPSPs) of 3 +/- 12 mV amplitude that lasted 4-30 msec. Six of the 13 MNs discharged action potentials upon LC stimulation. In the remaining 9 MNs, no observable potential change was registered after LC activation. Antecedent LC stimulation consistently potentiated the synaptic efficacy of testing dorsal root shocks. The enhancement of synaptic activation was antagonized by systemic injection of phenoxy-benzamine (3 mg/kg). These results suggest that facilitation of MNs by the LC is at least in part mediated by distal dendritic depolarization. Those MNs that exhibited augmented excitability but no demonstrable EPSPs may have been activated by norepinephrine-mediated synaptic modulation. PMID- 6265032 TI - Thyrotropin-releasing hormone (TRH) content of rat striatum: modification by drugs and lesions. AB - Two hours after injection, D-amphetamine sulfate (10 mg/kg, i.p.) lowered thyrotropin-releasing hormone (TRH) levels in rat striatum by 50%, but produced no significant changes in the TRH contents of hypothalamus, septum, brain stem or preoptic area. The effect peaked 2 h after amphetamine injection and declined slowly thereafter. The amphetamine-induced decrease in striatal TRH could be blocked by pretreatment with haloperidol or alpha-methyltyrosine, or by production of a 6-hydroxy-dopamine lesion in the ipsilateral substantia nigra. Amphetamine did not act by inhibiting protein synthesis in as much as cycloheximide did not similarly decrease striatal TRH. Kainic acid injected into the striatum lowered TRH by 30% after 5 days. In contrast, partial deafferentiation of the striatum (by cerebral hemitransection at mid-hypothalamic level) increased striatal TRH 2-3-fold, while lesions of the dorsal raphe did not significantly change striatal TRH. Thus TRH levels in rat striatum are closely regulated by dopaminergic and other neurotransmitter systems. PMID- 6265033 TI - Topography of the ACTH-immunoreactive neurons in the basal hypothalamus of the rat brain. AB - Cell bodies of the opiocortin neurons were stained immunocytochemically with ACTH antiserum and their location in the basal hypothalamus of the rat brain was mapped. They are present throughout the entire extent of the hypothalamus, from retrochiasmatic area to mammillary body. In the retrochiasmatic area they are a single, midline group horizontally oriented and lying close to the ventral surface. Throughout the extent of the median eminence, ACTH-ir perikarya are located in the arcuate nucleus, adjacent periventricular stratrum and internuclear space between arcuate and ventromedial nuclei; as a group, they are oriented in a dorso-lateral plane. In the mammillary region, the nucleus assumes a more horizontal orientation again, lying close to the ventral surface. No regional differences were noted in cell density except in the retrochiasmatic area and terminal portion of the mammillary region where they were approximately 30% fewer in number. PMID- 6265034 TI - Glutamic acid binding in goldfish brain and denervated optic tectum. AB - The binding of L-glutamic acid to goldfish brain membranes and changes in tectal binding following optic nerve denervation and regeneration were investigated. Saturable, reversible, and specific binding occurred to sodium-free washed membranes from goldfish brain at a single population of sites having an apparent Kd of 3.4 microM and a capacity of 10 pM/mg original tissue. Binding was enriched in crude synaptosomal (P2) subcellular fractions. There was a 10-fold regional variation in the concentration of binding sites. In pharmacological studies protection constants (Kp) (the concentration which resulted in a 50% inhibition of binding) ranged from 4 microM for glutamate to greater than 10 mM for GABA. Following eye removal, the total number of tectal glutamic acid binding sites was stable for 4 days, followed by a rapid loss in binding, reaching 40% of control at 24 days. After optic nerve crush and optic nerve regeneration, the number and concentration of binding sites was not different from control. The relationship between glutamate, nicotinic, and muscarinic receptor sites in the retinotectal pathway is discussed. PMID- 6265035 TI - A glial fibrillary acidic protein (GFA)-containing cell clone derived from mouse cerebella transformed 'in vitro' by SV-40. AB - A clonal cell line containing the glial fibrillary acidic protein (GFA) was derived from cultures of 14 day post-natal C57Bl mouse cerebella, transformed by SV-40. All the cells are GFA-positive - even in sparse exponential cultures - have been astroglial morphology and contain the intranuclear SV-40 T-antigen. PMID- 6265036 TI - Topographical and laminar localization of 2-deoxyglucose uptake in rat olfactory bulb induced by electrical stimulation of olfactory nerves. AB - Experiments were carried out to examine the topographical projection of the olfactory nerves to the olfactory bulb in the rat, using the Sokoloff [14C]2 deoxyglucose (2-DG) technique. Electrical stimulation of a medially located bundle of olfactory nerves produced a discrete zone of 2-DG uptake at the rostral pole of the bulb. Increasing stimulus strength yielded a slightly larger focus at this site. In contrast, electrical stimulation of laterally situated bundles of olfactory nerves resulted in a broad zone of activity extending along the lateral wall of the bulb, and increasing stimulus intensity produced a more extensive area of uptake. Laminar analyses provided information on the relation between activity in the glomerular layer, where the olfactory nerves terminate, and activity in deeper layers. The results support previous studies of the topographical projections of the olfactory nerves to the olfactory bulb. They also support the hypothesis that odor-induced 2-DG uptake in the olfactory bulb represents activation of groups of receptors in the olfactory epithelium whose axons terminate in activated glomerular regions in the olfactory bulb. PMID- 6265037 TI - Localization of synaptic responses in the in vitro turtle olfactory bulb using the [14C]2-deoxyglucose method. AB - Studies were carried out on the in vitro turtle olfactory bulb preparation with a modification of the [14C]-2-deoxyglucose (2-DG) technique. Electrical stimulation of either the dorsal or ventral division of the olfactory nerve produced broad bands of activity, spreading across laminae, in the corresponding half of the olfactory bulb. Pretreatment of the isolated preparation in a low calcium bath eliminated focal 2-DG uptake induced by electrical stimulation of the nerve. In contrast, pretreatment with the GABAergic antagonist, bicuculline, produced a notable increase in 2-DG accumulation. These findings are discussed in the light of the topographical innervation of the olfactory bulb by the olfactory nerve as well as the known synaptic organization of the olfactory bulb and the putative neurotransmitters operative in local circuits. PMID- 6265038 TI - Terminal sprouting of motoneurones is a local response to a local stimulus. AB - Terminal sprouting was visualized in silver stained whole mounts of rat sternocostal muscles after resecting one segmental nerve. Sprouts were only found near denervated muscle fibres. The effective diffusion range of the sprout inducing factor released by denervated fibres was 50--100 micrometers. Individual terminals of the same motoneurone sprout independently of each other and only when they intercept the sprout inducing factor. PMID- 6265039 TI - Interaction between central gray and nucleus raphe magnus: role of norepinephrine. AB - Recordings were made from single cells in the nucleus raphe magnus (NRM) of the rat. The response of these cells to electrical stimulation of the periaqueductal gray (PAG) was correlated with their response to iontophoretically applied norepinephrine (NE). It is shown that NE can cause excitation as well as inhibition of NRM neurons, although excitatory response was obtained more often than an inhibitory response. No correlation between the response to PAG stimulation and to NE was obtained. It is concluded that NE is not the transmitter that mediates the interaction between the PAG and NRM. PMID- 6265040 TI - Periaqueductal gray neurons response to microiontophoretically injected morphine in naive and morphine-dependent rats. AB - The attempt of this study was to investigate the direct effects of increasing doses of morphine on the neuronal activity of the periaqueductal gray in morphine naive and morphine-dependent rats. The microiontophoresis technique was used for this purpose. The four different responses induced by morphine exhibited dose related patterns. Naloxone antagonized these responses in about 40% of the cases. Differences were found in the sensitivity of the neurons of morphine between naive and morphine-dependent rats. The phenomena of acute tolerance, chronic tolerance and dependence have been found. The results of this study indicate the presence of different neural populations in the periaqueductal gray in relation to their response to morphine, supporting the notion that subpopulations of opiate receptors exist within this brain area. PMID- 6265041 TI - [Response of the ovary of the impuberal rat to gonadotropins and thyrotropin : changes in the permeability to K+ ions, cyclic AMP levels and protein synthesis]. PMID- 6265042 TI - [Ovarian calcium and fertilization in female rats receiving a subchronic overdose of vitamin D3]. AB - Calcium is increasing in ovaries of adult female rats when D3 vitamin is given by stomach intubation for 7 and 15 days. Histochemical studies show the presence of spherular chalky deposits specially in granulosa of some follicles. In the same times atresia becomes evident and fecondation is reduced. Chemical determination of calcium content of ovary show calcium accumulation in this organ. PMID- 6265043 TI - [Study of human serum ceruloplasmin by electron paramagnetic resonance : effects of various chemical agents]. PMID- 6265044 TI - Protection of actin against proteolysis by complex formation with deoxyribonuclease I. AB - G-actin bound to deoxyribonuclease I (DNase I) is resistant to digestion by trypsin and chymotrypsin. In the absence of DNase I, G-actin is cleaved by these proteases to yield a 33 500 molecular weight core protein which is not degraded further. The major sites of proteolytic action in the amino acid sequence of actin have been identified as being adjacent to residues arginine-62 and lysine 68 for trypsin and leucine-57 for chymotrypsin. These residues are rendered inaccessible to proteases in the buffer by complex formation with DNase I. Digestion of G-actin with pronase from Streptomyces griseus yields fragmentation patterns that are similar to those observed with trypsin and chymotrypsin. This is likely to be because the specificities of the major constituents of pronase resemble those of trypsin and chymotrypsin. Again, complex formation with DNase I protects the otherwise vulnerable bonds in actin against proteolysis. Incubation with subtilisin Carlsberg leads to complete digestion of G-actin. No subtilisin resistant core protein accumulates during the incubation. Protection of G-actin when complexed to DNase I is less than complete in this case but still is significant. This is interpreted in terms of the broad specificity of subtilisin and the observed fragmentation pattern of free G-actin when treated with subtilisin. PMID- 6265045 TI - A comparative proton magnetic resonance conformational study of the tRNA "wobble" nucleosides 5-carboxymethyl-, 5-methoxycarbonylmethyl-, and 5-carbamoylmethyl uridine. AB - The 270-MHz proton magnetic resonance spectra of 5-carboxymethyluridine, 5 methoxycarbonylmethyluridine, and 5-carbamoylmethyluridine have been obtained, and analyzed iteratively using LAOCOON 3. A standard treatment of the obtained data reveals that in each the 5-substituent produces no significant alteration in the furanose puckers, their equilibrium state, and the relative populations of the gg, tg, and gt exocyclic hydroxymethyl rotamers relative to uridine. The analogous similarity in furanose chemical shifts suggests that these derivatives favor the anti glycosyl state. The 5-substituent may act at the polynucleotide level in modulating the conformation and interaction(s) of the anticodon loop. PMID- 6265046 TI - Relationship between membrane fluidity and capping of receptors for concanavalin A. AB - The activities of a range of phenylalaninol-related compounds on capping of concanavalin A and induction of rounding of Chinese hamster ovary tsHl cells, as well as on the fluidity of phosphatidylcholine-cholesterol (1:1) liposomes, have been examined. These compounds include phenylalaninol, histidinol, leucinol, benzyl alcohol, benzylamine, 2-phenylethanol, 2-phenylamine, 3-phenyl-1-propanol, 3-phenyl-1-propylamine, and 3-phenylpropionic acid. The results indicate a strong correlation between the capacities of these compounds to enhance fluidity and their capacities to inhibit capping of concanavalin A. The specificity of this correlation is suggested by the finding that both types of capacities are poorly correlated with the capacities of the various compounds to induce cell rounding. PMID- 6265047 TI - Formation of angiotensin II by tonin from partially purified human angiotensinogen. AB - The renin substrate (angiotensinogen) has been purified from outdated human blood bank plasma. A 100-fold purification was achieved by ammonium sulphate protein fractionation and four successive chromatographic procedures. We show that tonin, a serine protease enzyme found in submaxillary glands of the rat, cleaves the human plasma angiotensinogen, devoid of tonin inhibiting factor(s), at a pH optimum of 5--5.5. It generates a pressor substance that was identified as angiotensin (A) II. The rate of cleavage of the human angiotensinogen preparation by 1 nmol of renin or tonin was calculated to be 1320 nmol AI/h for renin and 26 nmol AII/h for tonin. PMID- 6265048 TI - Purification and partial characterization of a plasma inhibitor of tonin. AB - A plasma inhibitor of tonin activity in the rat, was purified by ammonium sulfate precipitation, ion-exchange of chromatography, and gel filtration. Its purity was investigated by analytical electrophoresis on polyacrylamide gel and by ultracentrifugation sedimentation velocity. The molecular weight (360 000) of the purified inhibitor was determined by sodium dodecyl sulfate electrophoresis and its isoelectric point (4.5) by gel isoelectrofocusing. The Stokes radius (640 nm) was evaluated by gel filtration studies and a frictional ratio (f/fo) of 1.95 was calculated from the molecular weight and Stokes radius. Kinetic studies using angiotensin I as substrate showed that the inhibition of tonin by the purified inhibitor was noncompetitive and does not exceed 70%. Electrophoresis showed the same mobility for [125I]tonin bound to plasma proteins and for [125I]tonin bound to the purified inhibitor. The inhibitor may be a protein resembling half of the dimeric protease inhibitor rat alpha 1-macroglobulin or human alpha 2 macroglobulin. PMID- 6265049 TI - A rapid one-step method for the isolation of bacteroids from root nodules of soybean plants, utilizing self-generating Percoll gradients. AB - Bacteroids were isolated from the nodules of soybean plants by means of self generating Percoll density gradients. The entire procedure can be performed in less than 1 h using an ordinary refrigerated centrifuge and angle head rotor. All of the markers for cytosol and bacteroid fractions behaved in accord with other reports in the literature. Asparaginase, beta-hydroxybutyrate dehydrogenase, and alanine dehydrogenase were all localized in the bacteroid fraction. Invertase, phosphoenolpyruvate carboxylase, and leghaemoglobin were all found in the cytosol fraction. Very little (less than 7%) cross contamination between the fractions was observed. The isolated bacteroids were viable, and based on electron micrographs, were free from contaminating plant material. Since the entire procedure is performed isosmotically, very little damage to the bacteroids is likely to occur. No organic compounds, except Percoll, were added to the isolating media, thus aiding in the analysis of bacteroid and cytosol metabolites. PMID- 6265050 TI - Solubilization of membrane-associated phosphatidylserine synthase from Clostridium perfringens. PMID- 6265051 TI - Lithium and regression of oat-cell carcinoma. PMID- 6265052 TI - Aortic body tumor in a cow. PMID- 6265053 TI - Enzootic bovine leukosis. AB - The author emphasizes the significance of enzootic bovine leukosis in Canada. He describes in detail diagnostic methods, various types of the disease and methods of transmission. Various aspects of the disease in Canada are compared with those in other countries. Prevention and control are discussed in a Canadian context and include the current policies of the Government of Canada in relationship to this disease. The possibility of developing a certification program for herds free of the disease is also discussed. The paper includes incidence in various parts of Canada. PMID- 6265054 TI - Spontaneous pustular dermatitis in a newborn piglet associated with a poxvirus. AB - Poxvirus was recovered from pustular skin lesions in a newborn piglet. The lesions were present at birth, suggesting transplacental infection had occurred. The lesions were circular, 1 cm in diameter, and were found over the entire skin surface, bulbs of the heels, coronets, tongue and buccal mucosa. Histologically, cells in the stratum intermedium were undergoing ballooning degeneration and necrosis, coalescing to form vesicles. The lumen of vesicles was filled with fluid and inflammatory cells. Degenerating epithelial cell nuclei were often vacuolated and eosinophilic intracytoplasmic inclusions were in many ballooned cells. The size and morphology of the virions recovered from vesicular fluid, place them in the poxvirus group. PMID- 6265056 TI - Acquired dysfibrinogenemia in a hemophiliac with hepatoma: resolution of fibrinogen dysfunction following chemotherapy. AB - A 17-year-old male with previously undiagnosed congenital Factor IX deficiency (13%) presented with gastrointestinal bleeding and a hepatic mass. Prolonged thrombin and Reptilase times, which partially corrected with CaCl2 and a discrepancy between thrombin-clottable and immunoreactive plasma fibrinogen, suggested a dysfibrinogenemia. Laparotomy disclosed metastatic hepatoma. Adequate hemostasis was obtained with clotting factor replacement, but wound healing was delayed. Patient fibrinogen purified with 2.1 M glycine migrated normally on immunoelectrophoresis and 7.5% polyacrylamide-SDS gel electrophoresis. However, fibrin monomers prepared from purified patient fibrinogen displayed impaired aggregation at high and low ionic strengths when compared with fibrin monomers from normal and control Factor IX deficient subjects. Aggregation of normal monomers was delayed when mixed 1:1 with patient monomers. Fibrinopeptide release was normal, and total sialic acid content was similar to that of normal and control fibrinogens. Chemotherapy, consisting of 5-FU given via intra-arterial hepatic infusion, was accompanied by significant transient clinical improvement which coincided with correction of thrombin clotting times and fibrin monomer aggregation. Reappearance of fibrinogen dysfunction occurred with clinical deterioration prior to death from metastatic hepatoma and sepsis. This case is the first to corroborate the postulated tumor marker role of dysfibrinogenemia in a patient with hepatoma by documenting a direct relationship with response to chemotherapy. PMID- 6265055 TI - Equine colitis "X", still an enigma? AB - Colitis "X" is a sporadic diarrheal disease of horses with clinical signs of dehydration, electrolyte imbalances and "shock"-like features. Macroscopic and microscopic findings include signs of disseminated intravascular coagulation, necrosis of colonic mucosa and presence of large numbers of bacteria in the devitalized parts of the intestine. Recently published work suggests that the causative agent may be Clostridium perfringens, Type A, but the bacteria are recoverable only in the preliminary stages of the disease. Excess protein and lack of cellulose content in the diet is thought to be the trigger for the multiplication of the clostridial organisms. The pathological findings are pathognomonic, but clinically, a number of differential diagnoses have to be considered, such as intestinal accidents, salmonellosis, heavy metal intoxication and occlusive verminous arteritis. PMID- 6265057 TI - Neuroendocrine carcinoma (trabecular carcinoma) of the skin with ectopic ACTH production. AB - A case of ACTH-producing cutaneous neuroendocrine carcinoma occurring in the cheek of an 80-year-old woman is reported. The tumor was composed of undifferentiated cells which had a uniform round nucleus and scanty cytoplasm containing argyrophil granules. An ultrastructural study demonstrated neurosecretory-type granules in the cytoplasm of the tumor cells. Radioimmunoassay revealed an elevated level of ACTH in tumor tissue as well as in the plasma of the patient. This is believed to be the first documented case of ACTH-producing neuroendocrine carcinoma (trabecular carcinoma) of the skin. PMID- 6265058 TI - Dissociation in the response of the adenylate cyclase system to thyrotropin and prostaglandin E2 in human thyroid carcinoma tissue. AB - Because the existence of a damaged thyrotropin (TSH) receptor in thyroid tumors may be relevant in the perspective of a correct postsurgical therapy, the effect of TSH on cAMP intracellular accumulation in thyroid carcinoma (N = 16), follicular adenoma (N = 27) and normal tissue (N = 30) slices was studied and compared with that of nonspecific stimulus of thyroid adenylate cyclase-cAMP system, such as prostaglandin E2 (PGE2). While in all follicular adenomas a normal behavior of basal and post-TSH and -PGE2 stimulated cAMP accumulation was observed, basal cAMP levels were generally higher than in controls in 14 differentiated carcinomas, responses to TSH were reduced or absent, and response to PGE2 was close to normal. On the contrary, in two anaplastic carcinomas, both TSH and PGE2 produced a negligible modification of cAMP levels. Thus, in undifferentiated carcinomas, the adenylate cyclase-cAMP system seems to be altered; in differentiated carcinomas, the catalytic part of the system appears unaffected as it is PGE2-responsive. Therefore, some hypotheses are ruled out as an explanation for decreased sensitivity to TSH of differentiated carcinomatous cells. PMID- 6265059 TI - Pathogenesis and treatment of Paget's disease of the breast. AB - Fifty cases of Paget's disease of the breast treated surgically at The Johns Hopkins Hospital during the past 30 years were studied. Nineteen patients had Paget's disease confined to the nipple and 31 had an associated palpable tumor. An underlying intraductal or infiltrating duct carcinoma of the breast was present in each case. In six cases, the underlying tumor was 2 cm or more from the nipple with no apparent anatomic connection to the Paget lesion, and one case was encountered in whom intradermal Paget's disease develop in the area of a congenitally absent nipple. These findings support the theory of an intradermal origin for the Paget cell. Survival rates of patients with Paget's disease and a palpable breast mass were similar to those of patients with infiltrating duct carcinoma, the presence of axillary node metastases being the most important prognostic factor. Actuarial five- and ten-year survival rates were 22% and 9.9% for patients with positive nodes. The modified radical mastectomy is recommended as primary therapy for this group of patients. In contrast, none of the patients with Paget's disease of the nipple and no evidence of a palpable breast mass developed recurrent carcinoma. A total mastectomy without an axillary node dissection is the treatment of choice in this type of patient. PMID- 6265060 TI - Primary malignant fibrous histiocytoma of the aorta. AB - A rare case of malignant fibrous histiocytoma of the aorta is reported. Review of the literature revealed that primary tumors of the aorta are exclusively mesenchymal tumors that almost invariably pursue a fatal course. PMID- 6265061 TI - Absence of the ether lipid tumour marker in diethylnitrosamine-induced rat liver cell cancer. AB - Tissue levels of neutral O-alkylglycerolipids were measured in rat liver during the course of hepatocarcinogenesis produced by feeding diethylnitrosamine. Enzyme altered foci, not recognizable with conventional histological techniques, were shown to be present in specimens obtained after 3 or 6 weeks feeding the carcinogen. Frank hyperplastic nodules were present at 11 weeks and hepatocellular carcinoma were found in all rats at 18 weeks. At no point during the course of carcinogenesis did the liver show an increase in either-linked neutral glycerolipids, characteristic of animal tumours. On the contrary, lower levels of neutral O-alkylglycerolipids were found in tissues containing hyperplastic nodules or tumour. PMID- 6265062 TI - Stimulation of human polymorphonuclear leukocyte superoxide anion radical production by tumor promoters. AB - Comparison was made of the ability of the potent tumor promoter phorbol myristate acetate (PMA), as well as less active PMA analogs and non-phorbol ester tumor promoters, to stimulate superoxide anion radical (O-.2) production by human polymorphonuclear leukocytes (PMN). The rate of O-.2 production was found to correlate with the tumor-promoting activity of the phorbol esters as opposed to their inflammatory activity. Mezerein and telocidin B were slightly better stimulators of O-.2 production than PMA. Acetic acid was inactive. These data are discussed in terms of a possible role for O-.2 and other reactive oxygen species in tumor promotion. PMID- 6265063 TI - Formation and removal of benzo(a)pyrene adducts of DNA in hamster tracheal epithelial cells. AB - A cloned cell line derived from normal hamster tracheal epithelium has been characterized with respect to its response to the environmental pollutant and carcinogen benzo(a)pyrene [B(a)P]. These cells metabolize B(a)P to ultimate reactive forms as assayed by alkylation of DNA. Alkylation with radiotracer amounts of B(a)P was maximum at 8 hr, at which time 70% of the applied hydrocarbon had been converted to water-soluble forms. At longer incubation times, the rate of removal of adducts exceeded the rate of formation. When B(a)P containing medium was replaced with fresh medium at two or four hr, a subsequent biphasic removal of adducts occurred, a rapid removal for the first four hr postincubation and then a slower repair. About 50% of the DNA-bound hydrocarbon remained in DNA after 48 hr. Cells were able to divide in the presence of these lesions, undergoing five doublings (five days), while only 60% of the adducts were removed from the DNA. Integrity of DNA during this period was monitored by the alkaline elution technique. A toxic dose of B(a)P was required to cause any increase in the rate of elution. Minimal single-strand breakage was observed from two to eight hr of B(a)P treatment, but at 15 hr DNA appeared normal. Comparison was made with a nontoxic dose of methyl methanesulfonate which caused very rapid elution of DNA after only one hr treatment. At least 15 deoxyribonucleoside-bound B(a)P adducts were separated by high-pressure liquid chromatography. Four adducts, probably deoxyadenosine-B(a)P, were removed almost completely in 24 hr, while the others appeared to be poorly removed. The possible significance to neoplasia of persistent and repairable lesions is discussed. PMID- 6265064 TI - Regulation of urea cycle enzymes in transplantable hepatomas and in the livers of tumor-bearing rats and humans. AB - The levels of the five enzymes of the urea cycle were measured in normal 5-week old rats, in a transplantable hepatoma, and in the livers of tumor-bearing rats (host livers). The levels of all five enzymes were much lower in the hepatoma, although there was no exact correlation of the decrease in levels. In host livers, the levels were higher than in the tumors, but lower than in normal liver. The levels of all five urea cycle enzymes were positively correlated with dietary protein content in normal livers, in hepatomas, and in host livers. In fact, the hepatomas showed the greatest changes in response to diet. On all diets, the levels in host liver remained below those in normal liver, indicating that the decreased level was probably not due to preferential utilization of nutrients by the tumor. The levels of urea cycle enzymes in normal liver were not altered by a single injection of glucocorticoid, glucagon, or dibutyryl cyclic adenosine 3':5'-monophosphate. By contrast, in hepatoma, the levels were usually significantly elevated by the same treatment. In addition, the levels in host livers were always significantly elevated and were usually above those in normal animals, whether the latter were hormone treated or not. Injection of plasma from tumor-bearing rats into normal animals produced a decrease in the levels of all five enzymes; if glucagon was injected together with the plasma, large increases in levels were observed. This result supports the concept of a humoral factor produced by the tumor which affects the levels and the inducibility of urea cycle enzymes in host livers. Autopsied human primary hepatomas also showed levels of urea cycle enzymes below those in normal livers with host livers having intermediate values. A cell line derived from a human hepatoma showed induction of arginase by glucocorticoid in culture; in this, it resembled a cell line of the rat hepatoma. Tyrosine aminotransferase in human hepatoma cells was not induced by glucocorticoid; in this, it differed from the rat hepatoma cells where induction of this enzyme was observed. PMID- 6265065 TI - Benzo(a)pyrene binding to DNA in organ cultures of human endometrium. AB - Benzo(a)pyrene was found to bind to DNA in human endometrial tissue in vitro. Among specimens from 41 individuals examined, there was a 70-fold range in the observed specific activities of carcinogen binding to DNA. To determine whether this interindividual variability was correlated with the hormonally determined state of differentiation of the endometrial tissue, this population was subdivided to separate postmenopausal patients from premenopausal patients; among premenopausal patients, further division was made according to location within the menstrual cycle. Tissue obtained late in the proliferative phase or early in the secretory phase of the menstrual cycle had the highest mean specific activity of benzo(a)pyrene binding. In spite of the relatively small group sizes, the observed difference between this and the level of benzo(a)pyrene binding in the mid- and late secretory phases was statistically significant. The average binding level among the small number of patients studied who had entered a natural menopause was lower than the average binding for any of the subgroups of premenopausal patients and significantly lower than the mean for the whole population of premenopausal patients. PMID- 6265066 TI - Restricted expression of retrovirus nucleic acids and proteins in primate type C virus (gibbon ape leukemia virus-simian sarcoma virus)-initiated human B lymphoblast cultures. AB - Fresh human B-lymphoblasts established in culture following exposure of adult peripheral blood leukocytes to type C retroviruses of the simian sarcoma virus/simian sarcoma-associated virus-gibbon ape leukemia virus group were analyzed in detail for the presence of the infecting virus. Viral expression ranged from production of low levels of intact virus in a few cultures to the presence of viral RNA and protein in the absence of detectable of levels of complete virus in the majority of the cultures. In situ molecular hybridization assays using 3H-labeled complementary DNA and indirect immunofluorescence assays using antibody to purified viral protein indicated that the expression of viral RNA and proteins are preferentially expressed in only a fraction of the cells in some cultures. If expression of the infecting viral sequences is necessary for the sustained growth of these cells, then those cells detectably synthesizing viral RNA and proteins may be influencing the growth of the remaining virus negative cells. The lack of virus production in cultures synthesizing viral RNA and protein indicate that these human B-lymphocytes restrict the life cycle of these viruses at some step(s) after transcription of viral RNA or translation of viral protein. PMID- 6265067 TI - Levels of creatine kinase and its BB isoenzyme in lung cancer specimens and cultures. AB - Small-cell carcinomas of the lung (SCCL) have properties of amine-handling cells, and high levels of the key amine-handling cell enzyme L-dopa decarboxylase (EC 4.1.1.28) distinguish SCCL from most other lung cancers. SCCL tumor specimens and continuous cultures also are characterized by high levels of creatine kinase (EC 2.7.3.2) and its BB isoenzyme (CK-BB). Electrophoretic analysis of creatine kinase isoenzymes indicated that creatine kinase levels in SCCL were quantitatively but not qualitatively different from those in normal lung and other lung cancers. Supernatant fluids of SCCL cultures contained relatively modest concentrations of CK-BB but lacked detectable L-dopa decarboxylase activity. Variant SCCL cultures with altered morphology lost their amine-handling properties, including L-dopa decarboxylase activity, but retained high levels of CK-BB, indicating discordant expression of the two enzymes. CK-BB levels were measured in the sera of 67 patients having SCCL. Elevated levels were present in 16 of 41 patients (39%) having extensive-stage disease but in none of 26 patients (0%) having limited-stage disease. PMID- 6265068 TI - Aryl hydrocarbon hydroxylase activity in mouse, rat, and human mammary tumors. AB - Aryl hydrocarbon hydroxylase (AHH) activity was measured in microsomes from chemically induced and spontaneous mammary tumors of mice and rats and in 213 human breast tumors. Basal enzyme activities [pmol 3-hydroxybenzo(a)pyrene per mg protein per min] ranged from 0.05 to 0.5 for rat, 0.05 to 10 for mouse, and 0 to 40 for human tumors. For comparison, mean liver AHH activities were 13 in untreated rats and 100 in untreated mice. Thus, some human breast tumors had AHH activity exceeding that in rat liver. Injection of 80 mg beta-naphthoflavone per kg into tumor-bearing C3H/HeJ mice or Sprague-Dawley rats increased AHH activity to 10- to 70-fold over basal levels; there was no significant AHH induction in tumors from genetically "nonresponsive" DBA/2J or RF/J mice treated with beta naphthoflavone, alpha-Naphthoflavone in the incubation flask inhibited AHH activity in some human breast tumors and stimulated activity in others, probably reflecting the presence of multiple forms of cytochrome(s) P-450 in the human tumor population. AHH activity in human tumors was not correlated with their estrogen receptor content. Since several drugs used in cancer treatment are substrates for polysubstrate monoxygenases, high levels of AHH activity in some human tumors may play a role in their response to chemotherapy. PMID- 6265069 TI - Transforming growth factor production by chemically transformed cells. AB - Evidence is presented indicating that the chemically transformed AKR-MCA and C3H/MCA-58 murine cell lines produce "transforming growth factor(s)" capable of inducing a transformed morphology and the ability to grow in soft agar in nontransformed, anchorage-dependent indicator cells. Serum-free medium conditioned by exposure to the chemically transformed cells was chromatographed on a Bio-Gel P-60 column after dialysis and lyophilization. Using the nontransformed mouse AKR-2B cells as the indicator cells, a peak of soft agar growth-stimulating activity was detected in the molecular weight range of 10,000 to 12,000. The soft agar growth-stimulating activity in pooled fractions from the AKR-MCA cells was shown to be trypsin and dithiothreitol sensitive and relatively heat stable; the activity was not destroyed by heating to 56 degrees for 30 min or to 100 degrees for 3 min. The pooled material also caused stimulation of growth in the soft agar of rat NRK cells and stimulation of DNA synthesis in the AKR-2B cells. The quantity required to give significant competition for binding to the epidermal growth factor receptor was about one order of magnitude greater than that required for stimulation of soft agar growth. Further separation of these polypeptide(s) by carboxymethylcellulose chromatography revealed three apparent peaks of soft agar growth-stimulating activity. Epidermal growth factor receptor-competing activity cochromatographed with the early minor soft agar growth-stimulating peak, whereas the two major peaks of soft agar growth stimulating activity had no associated detectable competition for epidermal growth factor binding to its receptor. The data indicate that at least a major portion of the transforming growth factors produced by the chemically transformed cells is different from those described previously in murine sarcoma virus transformed mouse cells and human tumor cells. PMID- 6265070 TI - Electron spin resonance studies on normal human uterus and cervix and on benign and malignant uterine tumors. AB - Electron spin resonance (ESR) studies at -130 degrees have been made on frozen samples of normal human cervix and uterus and on frozen samples of various pathological conditions of the cervix and uterus including fibroleiomyoma and carcinoma. Fifty-five samples of normal cervix and endometrium, 40 samples of nonmalignant disturbances, 15 benign tumor samples, and 20 malignant samples were studied. Very strong ESR signals were seen in frozen powders and frozen intact samples of normal cervix and endometrium and in nonmalignant gynecological conditions. In many cases, the ESR signal was greatly decreased or even undetectable in cancer samples. The substance(s) responsible for the ESR signal in frozen intact tissue (g = 2.11 to 2.15) is decreased in concentration when the sample is ground to powder under liquid nitrogen, and an anisotropic signal (g = 2.002 to 2.035) then becomes much more evident. The ESR signals in intact and in powder samples are sensitive to temperature variations; the signals disappear around 0 degrees, and only the intact samples show significant recovery of signal on recooling. The anisotropic g values and temperature sensitivity in the powders may result from an organic peroxy radical that is more strongly associated with a metal ion in intact samples. PMID- 6265071 TI - Metal salts as promoters of in vitro morphological transformation of hamster embryo cells initiated by benzo(a)pyrene. AB - The hamster embryo cell bioassay has been used to study the effect of metal salts on morphological transformation. A synergistic enhancement of the transformation frequency was found for the combined treatment with organic carcinogens [benzo(a)pyrene, N-hydroxy-2-acetylaminofluorene, and 4-nitroquinoline 1-oxide] and nickel sulfate, cadmium acetate, or potassium chromate. Chromic chloride and zinc chloride did not induce transformation themselves, and they had no effect on the transformation frequency when tested in combination with benzo(a)pyrene. The synergistic effect between benzo(a)pyrene and nickel sulfate or cadmium acetate was also apparent when the cells were treated sequentially with the chemicals. When the cells were first exposed to benzo(a)pyrene, both nickel sulfate and cadmium acetate showed a promotion-like effect similar to that obtained with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate. Moreover, when 12-O tetradecanoylphorbol-13-acetate or benzo(a)pyrene were used as promoting agents, both nickel sulfate and cadmium acetate were able to initiate morphological transformation. The data suggest that the metal salts are more potent as promoters than they are as initiators. The present findings may be of importance in relation to carcinogenicity of metal compounds to humans. PMID- 6265072 TI - Partial purification of a common antigen in bovine lymphoma and its use in a lymphocyte blastogenesis assay. AB - An antigen was isolated from tumor cells derived from cases of bovine lymphoma which caused the in vitro blastogenesis of lymphocytes from nine of 13 (69%) adult cattle with lymphoma. Lymphocytes derived from five of 122 (4%) normal adult cattle also underwent blastogenesis while lymphocytes from three cases of the sporadic form of lymphoma did not respond. Blastogenesis of lymphocytes from normal cattle may have resulted from alloantigen activity in the antigen; however, normal lymph node antigen did not stimulate lymphocytes from normal adult cows or cows with lymphoma. Antigen derived from tumor was localized to the cell membrane and cytoplasm of tumor cells by indirect immunofluorescent staining using an antiserum prepared in rabbits. Specific fluorescence was reduced by the absorption of this antiserum with a crude tumor extract. The antiserum did not cross-react with normal lymph node antigen or viral components as demonstrated by immunodiffusion. With further refinement of the antigen, the blastogenesis assay may be of use in the early detection and study of the pathogenesis of lymphoma in adult cattle. PMID- 6265073 TI - Restriction endonuclease studies of hyperplastic outgrowth lines from BALB/cfC3H mouse hyperplastic mammary nodules. AB - The DNA's isolated from five mouse hyperplastic mammary gland outgrowth lines from BALB/cfC3H mice were digested with the restriction endonucleases PsTI, BamHI, or EcoRI; electrophoresed; and analyzed by Southern blotting and autoradiography. Proviral DNA sequences from the acquired C3H mouse mammary tumor virus were detected in the DNA of all five lines, indicating that they were infected. The DNA of the five hyperplastic lines contained more EcoRI and BamHI mouse mammary tumor virus proviral DNA fragments than did DNA from normal organs, suggesting that the hyperplastic tissues were composed of more homogeneous cell populations than was lactating mammary gland. Each hyperplastic line had unique and reproducible BamHI and EcoRI restriction (integration) patterns which were stable over as many as seven transplant generations. Three sublines, which originated from the same hyperplastic alveolar nodule, had unique integration patterns but also shared several fragments. On the basis of these observations, we propose that mouse mammary "hyperplasias" are clonal dominant premalignant neoplasms. PMID- 6265074 TI - Identification of cocarcinogens and their potential mechanisms of action using C3H10T 1/2 CL8 mouse embryo fibroblasts. AB - The cocarcinogenic action of five agents which increase microsomal mixed-function oxidase activity in vivo was examined in the C3H10T 1/2 CL8 transformation assay. The compounds studied were benz(a)anthracene, 5,6-benzoflavone, phenobarbital, pregnenolone-16 alpha-carbonitrile, and Aroclor 1254. After a 48-hr pretreatment with the agent, the cells were then treated with benzo(a)pyrene [B(a)P] and the agent for an additional 24 hr. All agents except for Aroclor 1254 increased B(a)P mediated transformation in C3H10T 1/2 CL8 cells. Benz(a)anthracene, 5,6 benzoflavone, phenobarbital, and pregnenolone-16 alpha-carbonitrile also increased the overall metabolism of B(a)P in C3H10T 1/2 CL8 cells to 9,10-dihydro 9,10-dihydroxybenzo(a)pyrene; 7,8-dihydro-7,8-dihydroxybenzo(a)pyrene, 9 hydroxybenzo(a)pyrene, and 3-hydroxybenzo(a)pyrene. Growth studies indicated that all four agents had no stimulatory effect which might have explained the increases in transformation frequency. This suggests that these agents exert their cocarcinogenic action via increases in the enzyme-mediated pathways of B(a)P metabolism. PMID- 6265076 TI - Characterization of the Epstein-Barr virus isolated from a cell line derived from a patient with American Burkitt's lymphoma. AB - Epstein-Barr viral (EBV) DNA is nearly always detectable in African Burkitt's lymphoma (BL) but is infrequently found in the histologically indistinguishable American BL. We have derived a tumor cell line from a patient with American BL which produces EBV, and we have compared this virus isolate [JLP(c)] with African BL EBV. The American JLP(c) virus immortalizes human umbilical cord lymphocytes in vitro, and its DNA is indistinguishable from African BL EBV DNA by nucleic acid hybridization and preliminary restriction endonuclease cleavage analysis. PMID- 6265075 TI - Phase I clinical investigation of 9,10-anthracenedicarboxaldehyde bis[(4,5 dihydro-1 H-imidazol-2-yl)hydrazone] dihydrochloride (CL216,942). AB - 9,10-Anthracenedicarboxaldehyde bis[(4,5-dihydro-1 H-imidazol-2-yl)hydrazone] dihydrochloride (CL216,942) is a new anthracene bishydrazone derivative that was evaluated in a Phase I clinical trial. The schedule of administration consisted of a single i.v. injection repeated at 4-week intervals. Twenty-eight patients received a total of 61 courses of the drug in a dose range of 20 to 280 mg/sq m. Leukopenia was the dose-limiting toxicity. It was of short duration and reversible. A drug-induced hypotension was noted at higher doses in three patients. The hypotension was not dose limiting, it was reversible, and it could largely be avoided by prolonging the drug infusion time to 1 hr. One patient with unsuspected severe coronary artery disease died of complications of myocardial infarction subsequent to a hypotensive episode. Significant phlebitis was also noted at higher doses of drug. This degree of phlebitis could be lessened by diluting the drug in larger volumes of fluid. Three patients experienced diaphoresis, nausea, palpitations, and chest discomfort at the conclusion of the infusions. None of the patients had electrocardiographic changes. Mild fever, alopecia, and nausea and vomiting were noted occasionally. One patient with a hypernephroma and one patient with hepatocellular carcinoma experienced partial responses of their tumors secondary to the drug. Phase II studies of CL216,942 are planned at a starting dose of 260 mg/sq m as a single dose repeated at 21- to 28-day intervals. PMID- 6265077 TI - Examination of Epstein-Barr virus and C-type proviral sequences in American and African lymphomas and derivative cell lines. AB - While Epstein-Barr viral (EBV) DNA is nearly always detectable in African Burkitt's lymphoma (BL), the relatively low frequency of BL in EBV-positive African children and the infrequent finding of EBV in American BL suggest that other cofactors may contribute to the malignant transformation. Among these possible cofactors are type C oncornaviruses. To evaluate this possibility, we screened the cellular DNA from 16 lymphomas (2 African, 14 American) and the DNA from 20 lymphoma-derived cell lines (4 African, 16 American) with a radiolabeled viral DNA probe from EBV and two oncornaviral probes (murine amphotropic 1504A virus and simian sarcoma virus). The radiolabeled EBV DNA probe hybridized with 18 of 36 tumor or cell line DNA's. Only 2 of 11 American BL tumors contained detectable EBV sequences. However, the cell lines derived from three EBV-negative tumors converted in vitro to EBV positivity, suggesting that some of the tumor cells could be infected with EBV. In contrast, none of the tumors or the cell lines derived therefrom hybridized with either the 1504A or the simian sarcoma virus probes, decreasing the likelihood that type C viruses are cofactors with EBV. PMID- 6265078 TI - Effect of low-density lipoprotein on the incorporation of benzo(a)pyrene by cultured cells. AB - Benzo(a)pyrene added to human plasma in vitro associated with the plasma lipoproteins, especially the low-density fraction. The influence of plasma low density lipoprotein on cellular uptake of benzo(a)pyrene was studied using WI-38, a human embryonic lung fibroblast line, and GM 1915, a skin fibroblast line derived from a patient with homozygous familial hypercholesterolemia. The WI-38 cells were low-density-lipoprotein receptor positive, and the familial hypercholesterolemia cells were receptor negative by standard binding studies with 125I-labeled low-density lipoprotein. Following 2 hr of incubation at 37 or 4 degrees, cell association of benzo(a)pyrene was determined with benzo(a)pyrene bound to lipoprotein or added at the same concentration to serum-free medium or medium containing delipidated serum. Uptake from delipidated or serum-free medium by both cell lines was linear with concentration, while incorporation of benzo(a)pyrene bound to low-density lipoprotein was much less and nonlinear at higher concentrations of lipoprotein. While low-density lipoprotein apparently influenced the availability of benzo(a)pyrene to the cell, no differences were noted in the incorporation of benzo(a)pyrene by WI-38 and familial hypercholesterolemia cells. Thus, benzo(a)pyrene entered the cells from low density lipoproteins despite the absence of specific receptors, apparently by a rapid redistribution between the lipoprotein and cell membrane. PMID- 6265080 TI - Effect of caffeine on induction of endogenous type C virus in mouse cells in vitro. AB - The effect of caffeine on the expression of murine endogenous virus in mouse cells induced by radiation and chemicals was studied. Postirradiation treatment of K-BALB cells with caffeine enhanced cell killing as well as the induction of xenotropic virus after ultraviolet light irradiation. The degree of enhancement for the virus induction was comparable to that for cell killing. On the other hand, colony-forming ability and the expression of xenotropic virus of K-BALB cells after X-irradiation were unaffected by caffeine. These data suggest a linear relationship between the degree of endogenous virus expression and the amount of lethal damages after irradiation. For induction by halogenated pyrimidines, a 24-hr incubation of AKR2B cells with caffeine after 5-iodo-2' deoxyuridine treatment resulted in marked suppression of the expression of ecotropic virus. On the contrary, in K-BALB cells, caffeine exerted only a small effect on 5-iodo-2'-deoxyuridine-induced expression of ecotropic and xenotropic viruses. These results indicate that, although using the same inducing agent, the pathway of endogenous virus induction may be different for AKR2B cells and for K BALB cells. PMID- 6265079 TI - Relationship between the levels of cyclic cytidine 3':5'-monophosphate, cyclic guanosine 3':5'-monophosphate, and cyclic adenosine 3':5'-monophosphate in urines and leukocytes and the type of human leukemias. AB - Cyclic cytidine 3':5'-monophosphate (cyclic CMP), cyclic guanosine 3':5' monophosphate (cyclic GMP), and cyclic adenosine 3':5'-monophosphate (cyclic AMP) contents of leukocytes and urines of leukemic patients have been investigated. We have studied four types of leukemia: acute myeloblastic leukemia; chronic myelocytic leukemia; acute lymphoblastic leukemia; and chronic lymphocytic leukemia. As controls, the cyclic nucleotide content of leukocytes and urines of healthy volunteers and patients with solid tumors selected for their normal hemogram has been determined. It has also been measured in phytohemagglutinin stimulated lymphocytes. Our data show that: (a) the concentration of cyclic CMP is always lower than that of cyclic GMP or cyclic AMP; (b) in urines, the concentrations of the three nucleotides are higher in patients than in healthy volunteers, the greatest differences being observed between the cyclic CMP concentrations of acute leukemia patients and controls; and (c) in white blood cells, cyclic AMP concentration is lower in leukemic than in normal cells. The cyclic GMP concentration is the same everywhere except in monoblastic cells and leukocytes from solid tumor patients. High cyclic CMP levels are associated only with acute leukemia, whether myeloblastic, monoblastic, or lymphoblastic, a fact which suggests that cyclic CMP could be a biochemical marker of hematopoietic stem cell malignancy. PMID- 6265081 TI - Adrenal response to serial cosyntropin stimulation after repeated high-dose prednisone administration in patients with lymphoma. AB - To determine if repeated courses of high-dose prednisone given to patients with lymphoma as part of multiple-drug chemotherapy programs would lead to progressive adrenal suppression, serial cosyntropin stimulation tests were performed. Four patients with diffuse histiocytic lymphoma (group 1) received prednisone for 5 days every 3 weeks for five courses, and five patients with Hodgkin's disease (group 2) received prednisone for 14 days every 4 weeks for six courses. Testing was done on Day 1 of each treatment course prior to the administration of therapy and after the final course of chemotherapy. In group 1 patients, there was no evidence of adrenal suppression after any of the courses of prednisone. The plasma cortisol increments after cosyntropin injection were also normal. In the group 2 patients, significant depression of basal plasma cortisol concentrations was observed after the first and fifth courses of prednisone, compared to the pretreatment values. The depression reflected the previous course of prednisone administration only and was not progressive with subsequent courses. The plasma cortisol increments after cosyntropin injection were normal despite depressed basal plasma cortisol levels. PMID- 6265082 TI - Intensive induction chemotherapy in 54 patients with small cell carcinoma of the lung. AB - Fifty-four patients with localized and extensive small cell carcinoma of the lung and no prior therapy were treated with intensive induction chemotherapy. The induction regimen consisted of two courses of high-dose cyclophosphamide, doxorubicin, and VP-16-213. The objective response rate was 78% (42 responses among 54 patients), with 14 complete (26%) and 28 partial (52%) responses. The median survival time for the entire group of patients is 378 days, with a projected 2-year survival rate of 22%. The most significant determinant of survival was the attainment of a complete response. Tumor progression in most relapsing patients occurred at the sites of initial involvement. Toxicity was significant, as expected, but treatment-related mortality did not exceed that of less intense regimens. Despite the use of such intensive induction regimens, the major challenge in the therapy for small cell carcinoma remains the achievement of more durable complete remissions. PMID- 6265085 TI - Complications in the treatment of small cell carcinoma of the lung. PMID- 6265083 TI - Phase II study of AMSA in lung cancer. AB - Ninety-one assessable patients with advanced oat cell and non-oat cell carcinoma of the lung were given AMSA on an intermittent every-3-week schedule. Starting doses ranged from 55 to 120 mg/m2, depending on the presence and severity of hepatic dysfunction. Three partial responses (two squamous cell carcinomas, one adenocarcinoma) of short duration were documented. The major toxic effect was leukopenia (44%). AMSA does not appear to have sufficient antitumor activity to warrant further investigation in advanced lung cancer. PMID- 6265084 TI - Ifosfamide: a weekly dose fractionated schedule in bronchogenic carcinoma. PMID- 6265087 TI - Collateral blood supply to an autotransplanted kidney. AB - Collateral lumbar arterial blood supply to an autotransplanted kidney was angiographically documented in a patient with bilateral Wilms' tumor and postoperative transplant renal artery stenosis. During autotransplantation, most collateral pathways are interrupted. The development of a collateral circulation after autotransplantation may be postulated to begin with a vascular response to postoperative inflammation and adhesions. The small anastomotic pathways so formed may then dilate in response to ischemia resulting from renal artery stenosis. PMID- 6265086 TI - Retroperitoneal malignant fibrous histiocytoma: the angiographic and computed tomographic features of an unusual tumor. AB - Malignant fibrous histiocytomas are uncommon retroperitoneal soft tissue tumors. We report a case of a malignant fibrous histiocytoma of the retroperitoneum that was anmgiographically hypervascular and indistinguishable from renal cell carcinoma. Computerized tomography of the abdomen demonstrated extensive psoas muscle infiltration by tumor. This feature may be useful in differentiating a renal cell carcinoma from a primary retroperitoneal sarcoma. PMID- 6265088 TI - [Biological and immunological activity similar to digitalis glycosides of synthetic ACTH and some sex hormone 14-hydroxyderivatives (author's transl)]. PMID- 6265089 TI - [Morphological demonstration of hepatitis B virus surface antigen in liver cirrhosis, fibrosis and hepatocellular carcinoma (author's transl)]. PMID- 6265090 TI - Ultrastructure of neurons in the ventromedial nucleus or the hypothalamus in ovariectomized rats with or without estrogen treatment. AB - The fine structure of the ventrolateral and dorsomedial subdivisions of the ventromedial nucleus (VMN) of the hypothalamus was examined in ovariectomized/control and ovariectomized/estrogen-treated rats to compare neurons of these areas to other neurons (specifically the ventrolateral thalamus), and to determine the effects of estrogen on these cells. The neurons of the VMN contain a large nucleus with a prominent nucleolus, rough endoplasmic reticulum (RER), polysomes, a Golgi complex, coated, uncoated and dense-cored vesicles, lysosome-like bodies, inclusion bodies, multivesicular bodies whorl bodies and myelin figures. Similar organelles were present in the neurons of the ventrolateral thalamus, although polysomes wee more prominent, and the cells lacked dense-cored vesicles in the perikarya. Differences in the cells of the VMN between ovariectomized/control and ovariectomized/estrogen-treated rats included a more conspicuous stacking of the RER and greater number of dense-cored vesicles in the estrogen-treated group in both the ventrolateral and dorsomedial subdivisions. In both areas the differences were statistically significant, although more marked in the ventrolateral subdivision. In both VMN subdivisions, the increased stacking of the RER could be correlated with the greater number of dense-cored vesicles and may reflect increased biosynthesis of a secretory product. PMID- 6265091 TI - Evidence for FSH-like material in ACTH granules of certain corticotropic cells in the pituitary of the pig. AB - The ultrastructural immunocytochemical peroxidase-antiperoxidase technique used on serial sections reveals that certain corticotropic cells contain both ACTH and FSH beta, but not LH beta (ACTH/FSH cells). To determine the specificity of the anti-FSH beta staining in these cells, immunocytochemical absorption experiments were performed. The results indicate that (1) anti-FSH beta and -ACTH antisera are bound to different antigens in the corticotropic cell, and (2) anti-FSH beta staining is specific for a FSH-like antigen. In the ACTH/FSH cells both hormones are stored in the same secretory granules, distributed among other granules that contain only ACTH. PMID- 6265092 TI - The innervation of the hepatic portal vein in the rabbit: ultrastructural evidence against "purinergic" neurotransmission. AB - The relative density of adrenergic and non-adrenergic nerves in the hepatic portal vein of the rabbit has been determined ultrastructurally. Adrenergic nerves were visualised with the modified chromaffin procedure of Tranzer and Richards (1976). Nearly equal numbers of adrenergic and non-adrenergic nerve profiles were found, indicating a much greater density of innervation by non adrenergic nerves than that described by Burnstock et al. (1979) using light microscopic histochemical methods. These results imply that part of the argument used by Burnstock et al. (1979) to support "purinergic" transmission in rabbit portal vein is probably invalid. PMID- 6265093 TI - Morphological and histochemical study of the endometrical effects of ovral in the baboon. AB - In an effort to better understand changes induced by hormonal contraceptives, a group of female baboons were administered Ovral for a period of 9 months. During this time the endometrium was sampled by transcervical uterine biopsy from both the treated animals and from a control group. The biopsies were all obtained between 10 and 14 days of the treatment cycle or the normal menstrual cycle. The endometrial glandular cells from the treated animals exhibited an accelerated maturation compared with the controls. Ultrastructurally this was reflected by increased cell size, numerous long, slender microvilli on the apical membranes, and increased development of the Golgi complex. Differences were also observed in the predominant type of granule seen in the apical cytoplasm. After 3 and 6 months of treatment with Ovral, no significant differences were noted between groups or between animals within a group. However, after 9 months of treatment, the endometrium displayed differences from the earlier experimental groups as well as individual variations. The functional correlates of these observations are discussed and compared to human endometrium. PMID- 6265094 TI - Ultrastructural immunocytochemical evidence of the presence of a peptide related to ACTH in granules of LHRH nerve terminals in the median eminence of the guinea pig. PMID- 6265097 TI - DNA supercoiling: another level for regulating gene expression. PMID- 6265096 TI - Cytological evidence for activation of neuroendocrine cells in the parvocellular preoptic nucleus of the goldfish hypothalamus following pharmacological adrenalectomy. AB - The nucleus preopticus (NPO) of the goldfish hypothalamus is composed of parvocellular (NPOpc) and magnocellular (NPOmc) neurosecretory neutrons. The cytology of NPOpc and NPOmc neurons was examined with light and electron microscopy following pharmacological adrenalectomy with the adrenocortical inhibitor, metopirone. After five days of metopirone administration, light microscopy revealed a significant increase in nuclear area of NPOpc, but not of NPOmc, neurons. Ultrastructural examination of NPOpc neurons revealed two cell types, PC1 and PC2 neurons, which could be distinguished by the relative abundance and the size of the neurosecretory granules in the cytoplasm. The ultrastructural appearance of the NPOmc neurons revealed a single cell type containing abundant neurosecretory granules. Following five days of metopirone administration, the ultrastructural appearance of the PC1 neurons indicated a state of enhanced secretory activity. Metopirone had no observable effect on the appearance of the PC2 or NPOmc neurons. These observations demonstrate that PC1 neurons are activated under the conditions of pharmacological adrenalectomy and suggest that the secretory activity of these neurons is inhibited by adrenocorticosteroids. PMID- 6265095 TI - Cytochemical localization of adenylate cyclase activity in the rat anterior pituitary. AB - The cytochemical localization of adenylate cyclase was studied in relation to the secretory function of the anterior pituitary glands of male rats. The reaction product of adenylate cyclase was localized on the outside of plasma membranes, but was not detected intracellularly. High activity of adenylate cyclase was detected on somatotrophs and microvilli of follicular cells, whereas no activity was found on thyrotrophs or corticotrophs. Although most of the gonadotrophs showed little or no adenylate-cyclase activity, some was detected in a small number of gonadotrophs in the central portion of the gland. In somatotrophs, activity was not detected on the plasma membranes facing perivascular spaces where exocytotic extrusion of secretory granules was frequently observed, although the remaining areas of plasma membranes of the same somatotrophs were associated with high levels of adenylatle-cyclase activity. These findings indicate that the association of a high level of adenylate-cyclase activity is not directly related to the ability of the plasma membranes to fuse with secretory granule membranes. PMID- 6265098 TI - Aggregation in Dictyostelium discoideum. PMID- 6265099 TI - Human V kappa immunoglobulin gene number: implications for the origin of antibody diversity. AB - To assess the relative contributions of germline versus somatically mutated genes in the human immune system, we have examined the size of the kappa light-chain variable region (V kappa) gene pool. Two cloned kappa subgroup 1 (V kappa 1) gene probes detected the same family of 15 to 20 crosshybridizing restriction fragments in human DNA, whereas flanking region probes detected fewer hybridizing fragments. Most of the hybridizing bands represent single-copy genes, as judged by a "'gene titration" experiment. Furthermore, the number of hybridization bands is a good estimate of the haploid gene number, since we observed little polymorphism of restriction sites in the V kappa locus of eight unrelated people. A cloned V kappa 3 probe hybridized to essentially the same 15--20 genes in human DNA as the V kappa 1 probes. These results strongly suggest that a discrete family of 15--20 genes constitutes a large proportion of the V genes from three of the four V kappa subgroups. The small number of V kappa genes in the human genome supports the idea that somatic mutation plays a major role in the origin of antibody diversity in man. PMID- 6265100 TI - The structure of the human histone genes: clustered but not tandemly repeated. AB - We have isolated five clones containing human histone genes from a human genomic DNA library, using a cloned X. laevis histone H4 cDNA probe (pX1ch4). Each genomic clone has been mapped and the locations of the histone genes have been determined by blot hybridization and hybridization-selection of human histone mRNA. In contrast to the organization of previously characterized histone genes, the human histone genes are clustered in the genome but are not arranged into recognizable repeating units. The extreme lack of organization of the human histone genes may reflect the diminished requirement for rapid synthesis of large quantities of histone proteins during mammalian early development. PMID- 6265101 TI - Unusual structure of the FB family of transposable elements in Drosophila. AB - We have analyzed the construction of the members of the foldback (FB) family of transposable elements in Drosophila by detailed restriction analysis, cross hybridization, electron microscopy, in situ hybridization and nucleotide sequence determination. The members are heterogeneous, with both the inverted terminal repeats and the total element sizes extremely variable. Nevertheless, the ends of the inverted repeats represent closely conserved sequences, similar for all members. Sequence analysis of one of the FB elements revealed an unusual constriction. There are scattered multiple copies of a 10 bp sequence near the inverted repeat termini; 300 bp from the end this sequence is expanded to a 20 bp repeat, and 500 bp from the end it is again expanded to a 31 bp repeat. A large part of the inverted repeats consists of contiguous tandem repeats of this 31 bp sequence. We also find two differences between the two copies of the inverted repeat, one of which involves an intact copy of the 10 bp sequence mentioned above. Sequence analysis of a corresponding DNA segment without this transposable element shows that insertion generates a 9 bp duplication at the target site. In situ hybridizations to polytene chromosomes show about 30 widely scattered positions with homology. Comparison of the hybridization patterns for three strains shows significant interstrain and intrastrain differences in chromosomal locations. PMID- 6265102 TI - Ribosomal RNA gene amplification in Tetrahymena may be associated with chromosome breakage and DNA elimination. AB - The chromosomal DNA sequence adjacent to one end of the single ribosomal RNA gene (rDNA) in the micronucleus of Tetrahymena has been isolated by cloning. Using this sequence as a hybridization probe the organization of the same sequence in the somatic macronucleus has been examined. The restriction enzyme digestion maps of this sequence in the two nuclei are very different. Detailed mapping studies suggest that a chromosome break has occurred near the junction between the rDNA and the neighboring sequence during the formation of the macronucleus. As a result the flanking sequence is located near a free chromosome end in the macronucleus. The existence of such a linear DNA end has also been shown by digestion with the exonuclease Bal 31. In addition to the breakage, some sequences at this junction are found to be eliminated from the macronucleus. This observation has been interpreted in relation to the mechanism of rDNA amplification, which in Tetrahymena generates extrachromosomal rDNA molecules during macronucleus development. PMID- 6265103 TI - Synthesis and stability of developmentally regulated dictyostelium mRNAs are affected by cell--cell contact and cAMP. AB - Postaggregation Dictyostelium discoideum cells contain 3000 mRNA species that are absent from preaggregation cells; these aggregation-dependent sequences comprise 30% of the mass of mRNA in these cells. We show that the synthesis and stability of these regulated mRNA sequences are affected by both cell--cell contact and cAMP. Three independent assays are used to quantitate these mRNAs: in vitro translation followed by two-dimensional gel analysis of the protein products; hybridization of gel-separated RNAs to cloned DNAs; and hybridization of mRNA to a cDNA probe specific for the population of regulated sequences. In postaggregation cells, the half-life of both the developmentally regulated mRNAs and the constitutive mRNAs present throughout growth and differentiation is the same--about 4 hr. Following disaggregation, all of the late mRNA sequences are degraded and decay with a half-life of 25 to 45 min. The constitutive species are unaffected; 2.5 hr after disaggregation, the ratio of late to constitutive mRNAs is about 6% that of normal plated cells. Addition of cAMP to cells that have been disaggregated for 2.5 hr (or longer) restores the level of most late mRNAs within 3 hr. We conclude that cAMP stimulates the synthesis of these mRNAs and may also act to stabilize them in the cytoplasm. This effect of cAMP is dependent on the cells having been in contact with other cells; cAMP has no effect on the levels of mRNA in suspension-starved, aggregation-competent cells that have never formed cell--cell aggregates. PMID- 6265104 TI - The involvement of cAMP in lymphocyte capping. PMID- 6265105 TI - [Isolation of orbiviruses from the Kemerovo complex in the tick Ixodes ricinus in the Czech Socialist Republic (author's transl)]. PMID- 6265106 TI - Induction of aldehyde dehydrogenase by polycyclic aromatic hydrocarbons in rats. AB - Short-term intragastric administration of selected polycyclic aromatic hydrocarbons (100 mg/kg daily for 4 days) to male Wistar rats resulted in marked changes in liver cytosolic aldehyde dehydrogenase activity. Non-carcinogenic anthracene, phenanthrene and chrysene produced a 2.5--3-fold increase in the activity assayed with propionaldehyde as substrate and NAD as coenzyme. Weakly carcinogenic 1,2-benzanthracene enhanced aldehyde dehydrogenase activity 9-fold and the potent carcinogens 3,4-benzpyrene and 3-methylcholanthrene 30-fold. With benzaldehyde as substrate and NADP as coenzyme the differences between the groups were even more pronounced. Somewhat similar but less manifest effects on aldehyde dehydrogenase activity were detected also in the liver microsomes and in the postmitochondrial fractions of the small intestinal mucosa. On the basis of their ability to induce aldehyde dehydrogenase activity the compounds could be divided into three groups. This classification was found to correlate well with the carcinogenic potency of the compounds. It appeared that the exposure to polycyclic aromatic hydrocarbons, especially the carcinogenic ones, was followed by synthesis of a new aldehyde dehydrogenase form. This new form was differentiated from the normally existing cytosolic aldehyde dehydrogenase by its ability to oxidize benzaldehyde in the presence of NADP. PMID- 6265107 TI - [Vascular deteriorations in subjects exposed to vibrations (author's transl)]. PMID- 6265109 TI - Alternating non-cross-resistant drug combinations in the treatment of metastatic small-cell carcinoma of the lung. AB - In a randomized trial of the Southeastern Cancer Study Group, patients with metastatic small-cell lung carcinoma were treated with a combination of cyclophosphamide (500 mg/m2 I.V.), Adriamycin (50 mg/m2 I.V.), DTIC (250 mg/m2 I.V.), and vincristine (1 mg/m2 I.V.) every 4 weeks for three cycles. Complete and partial responders to this induction regimen were then randomized to receive either the same combination every 4 weeks for an additional six cycles versus a non-cross-resistant drug combination of BCNU (100 mg/m2 I.V.), procarbazine (100 mg/m2 p.o. daily x 10 days), methotrexate (25 mg/m2 I.V.), and vinblastine (5 mg/m2 I.V.) every 4 weeks for six cycles versus alternating treatments with the two regimens for a total of six cycles of therapy. Patients who were less than good responders received six cycles of the non-cross-resistant drug combination. Of 202 evaluable patients, 40% responded (complete + partial responses) to induction; the complete response rate for the whole group was low (14%). Patients randomized to the BPMV combination, or crossed over to it, failed to improve upon their response to induction. Patients who responded to induction had a median survival of 41 weeks versus 20.6 weeks for the nonresponders, p less than 0.001. Performance status greater than or equal to 60%, and absence of prior radiotherapy were associated with improved survival (30 and 31.5 weeks, respectively). The toxicity of these regimens was acceptable. Failure to improve on results of our earlier protocol were probably due to the long (weeks) interval between treatments, inclusion of a relatively inactive but toxic drug (DTIC) in the induction combination which limited doses of the more active agents, and the use of a non-cross-resistant drug regimen which was inactive. PMID- 6265108 TI - [Utility of angiography in the diagnosis and localization of hepatic carcinomas]. AB - In the field of malignant primitive hepatic tumours, the use of ultrasonic methods and C.A.T. has made a considerable contribution to diagnosis and topographical localisation of such tumours. In addition, hepatic biopsy supplies the histological diagnosis. However it is only by angiography that it is possible to evaluate the involvement of the lobes and segments, supplying the character of invasiveness or otherwise of the lesion through demonstration of the arterial peduncle, and thus giving the surgeon the essential elements for a therapeutic approach. Furthermore, in the case of a monofocal lesion, it is only angiography that can establish the usefulness or otherwise of surgical therapy (William M. - Richard P. J. - Philip C. G. - Robert C. Lim, 1979). The purpose of the work is to examine the angiographic readings, which allow: 1) a diagnosis of hepatic expansive formation to be made, with definition of its nature (bening or malignant); 2) the growth character of the lesion to be characterised through evaluation of the involvement of the vascular structures. PMID- 6265110 TI - VP-16-213 therapy in patients with small-cell carcinoma of the lung after failure on combination chemotherapy. PMID- 6265111 TI - Kinetically scheduled therapy for extensive small-cell lung cancer. AB - Nine patients with extensive small-cell lung cancer were treated with a kinetically scheduled combination of cyclophosphamide, methotrexate by infusion, Adriamycin, and vincristine. There were two partial responses. No complete responses were noted. All patients progressed within 25 weeks of the initiation of therapy. In contrast to previously reported success with a similar kinetic schedule, we have found it to be ineffective in patients with extensive disease. Higher-dose therapy may be necessary to achieve better results in extensive small cell lung cancer. PMID- 6265112 TI - Retrospective validation of a new staging system for Wilms' tumor. AB - Prognostic significance has been ascribed to certain clinicopathological features of the Wilms' tumor. Examples are size, vascular invasion, histologic characteristics, tumor rupture, and lymph nodal involvement. Several of these were arranged into a grouping system, and used in a cooperative clinical trial, the first National Wilms' Tumor Study (NWTS). Detailed clinicopathologic information was accumulated for each patient entered in the study, and these data were analyzed with respect to their prognostic import. Factors found to be of significance were rearranged into a proposed staging system, believed more likely to be predictive of outcome for patients with tumor spread beyond the kidney confines, but without distant metastases (Groups II and III). The postulated discriminatory superiority was tested using Group II and III patients entered in the second NWTS. The same children were reassigned retrospectively to Stages II and III, and the outcomes compared. Statistically significant differences were noted between Stages II and III, but not for Groups II and III. These results encourage the use of the new staging system in the third NWTS. PMID- 6265113 TI - Cystosarcoma phyllodes. Diagnosis and management. AB - The diagnosis and management of cystosarcoma phyllodes is analyzed by reviewing the literature and presenting cases from our institution. This rare neoplasm of the female breast represents less than 1% of all breast tumors. Most patients present in the fourth and fifth decades of life. The predominant complaint is a palpable mass in the breast. Systemic manifestations occur after metastases have developed. Treatment is surgical excision. There is some controversy, however, over which type of surgical procedure should be performed. We recommend total mastectomy. Local recurrence and metastases do occur and have been related to inadequate surgery and various histological characteristics (mitotic activity, tumor margin, and stromal cellular atypia). PMID- 6265114 TI - Characterization of antibodies to orthopoxviruses in human sera by radioimmunoassay. AB - Serological surveillance of suspected orthopoxvirus infections in man is important for confirming the success of the worldwide smallpox eradication programme. An adsorption radioimmunoassay (RIA) was used to differentiate sera from patients who were naturally infected with human monkeypox or variola virus, and individuals who were immunized with vaccinia virus. The antisera were adsorbed with uninfected chicken chorioallantoic membrane (CAM) and vaccinia infected CAM before reacting in RIA with vaccinia, monkeypox, and variola antigens. Each serum group showed characteristic patterns of residual antibody activity which made it possible to identify antibody specificities.When 45 human sera were tested by this method, 71% were identified as having vaccinia, variola, or monkeypox adsorption characteristics, while the remaining 29% could not be identified. Of the identified sera, 9 were characteristic of vaccinia, 8 of variola, and 15 of monkeypox. Six of the 15 monkeypox sera were virologically confirmed monkeypox infections, 6 were suspected monkeypox infections but were not virologically confirmed, and 3 were of unknown aetiology.The adsorption RIA provides a method of identifying serologically the poxvirus responsible for infection long after the acute phase of illness. PMID- 6265115 TI - [Comparative effect of vitamin D3 and Solanum malacoxylon on blood calcium, cytochrome P-450 induction and use of retinol in rats receiving a rachitogenic diet]. PMID- 6265116 TI - [Effect of collagenase on the permeability of the glomerular basement membrane in the rat kidney]. AB - Recently, several authors have emphasized the role of negative sites located in th laminae rarae of the glomerular basement membrane (GBM), in restricting glomerular permeability to anionic macromolecules. In this work, we point out that ultrafiltration properties involve integrity of the GBM. Indeed after intravenous perfusion of bacterian collagenase, anionic ferritin permeates the GBM though negative site distribution (as shown by fixation of colloidal iron) is unaffected. PMID- 6265117 TI - [Chromatin structure with no nucleosomes: dissociated SV40 virus]. AB - The mild dissociation of SV40 virus particles at pH 7.5 yields a nucleoprotein complex containing all the capsid proteins and histones of the intact virion. Electron microscopic observations show a bead-on-a-string structure comprising about 70 particles 7 nm in diameter along the viral DNA. No particle of nucleosome size was visible. The compaction of DNA in this complex is lower than 2 and is likely to be close to unity. PMID- 6265118 TI - In vitro effects of E coli endotoxin on K+-activated para-nitrophenylphosphatase activity and ouabain binding in dog hearts. AB - The in vitro effect of E coli endotoxin on the activity of K+-activated paranitrophenylphosphatase (K+-PNPPase), an enzyme which represents the partial activity of (Na+ + K+)-ATPase enzyme system, was studied in isolated adult dog heart myocytes. The results were correlated with ouabain-binding studies. Endotoxin had an inhibitory effect on the Vmax for K+ activation as well as the Vmax for Mg++ and para-nitrophenylphosphate (PNPP) saturation. The inhibition was concentration-dependent and noncompetitive with K+, Mg++, and PNPP and furthermore, reversible. Endotoxin did not displace the bound 3H-ouabain from receptor sites nor did it affect the capacity of ouabain binding, indicating that the total enzyme concentration was not altered. From these findings, it is concluded that endotoxin in vitro affects the myocardial (Na+ + K+)-ATPase enzyme system by decreasing the turnover number of the enzyme molecule. The ability of endotoxin to modify myocyte membrane-associated enzyme activity may be responsible for altered heart metabolism and function in endotoxemia. PMID- 6265119 TI - Chronic opiate receptor occupation and increased lethality in endotoxemia. PMID- 6265120 TI - Relative location of alpha- and beta-adrenoceptors to sites of release of sympathetic transmitter in the rabbit facial vein. AB - We studied alpha- and beta-adrenoceptor-mediated responses of rabbit facial vein rings to adrenergic stimulation to determine the location of the two types of receptors in relation to the sympathetic nerve terminals. Transmural electrical nerve stimulation (TNS) at low frequency elicited large beta-receptor-mediated relaxation responses in rings pretreated with phentolamine (6 x 10(-7)M). These responses were significantly greater than the corresponding alpha-receptor mediated contractions in rings pretreated with propranolol (10(-6)M). Blockade of neuronal uptake with desmethylimipramine (DMI, 10(-7)M) increased significantly the neurogenic relaxation but had little effect on neurogenic contractility. DMI pretreatment caused a shift to the left (x 5.6) in the relaxant dose-response curve to exogenous l-norepinephrine (NE). The NE contractile dose-response curve was also shifted to the left after DMI pretreatment but by a significantly smaller amount (x 3.1). Neurogenic activation of beta-receptors evoked almost maximal relaxations in facial vein rings (85% at 2 Hz), whereas the maximum neurogenic contraction was approximately half the maximum contraction with exogenous NE (40% at 6 Hz). These results imply that the beta-adrenoceptors in the rabbit facial vein are located in close proximity to sites of adrenergic transmitter release and neuronal reuptake, whereas the alpha-receptors are more distant. PMID- 6265121 TI - Toxic megacolon. Part I: Pathogenesis, diagnosis and treatment. PMID- 6265122 TI - Primary hepatic cancer in alcoholics. PMID- 6265124 TI - Tolerance to the effects of delta 1-tetrahydrocannabinol on the pressor responses to noradrenaline in rats. AB - 1. The depressor response, but not the cardiac slowing response, to the acute intravenous administration of delta 1-THC (1 mg/kg) was significantly reduced in urethane anaesthetized rats, which had been treated with daily injections of delta 1-THC (2 mg/kg, i.p.) for 10 days (P less than 0.01). 2. No significant differences in either the depressor or the negative chronotropic effects of an acute intravenous injection of delta 1-THC (1 mg/kg) were observed in anaesthetized rats which had been treated with PVP (8 mg/kg per day, i.p.) for 10 days. 3. The depressor and cardiac slowing responses to an acute intravenous dose of delta 1-THC (1 mg/kg) were not significantly different between delta 1-THC- and PVP-treated animals which had been pithed. 4. The potentiating effects of delta 1-THC on the pressor responses to intravenously administered noradrenaline were significantly reduced (P less than 0.001) in urethane anaesthetized rats which had been treated with delta 1-THC, but not in anaesthetized PVP-treated animals. 5. Tolerance to the potentiating effect of delta 1-THC on the responses to noradrenaline has also been demonstrated in anaesthetized delta 1-THC-treated rats, but not in pithed delta 1-THC treated ones. 6. It is concluded that the development of tolerance to the depressor action of delta 1-THC, and its potentiating effect on the noradrenaline pressor responses requires the presence of an intact central nervous system. PMID- 6265123 TI - Assessment of oral ascorbate in three children with chronic granulomatous disease and defective neutrophil motility over a 2-year period. AB - Two brothers and their sister with chronic granulomatous disease, elevated levels of serum IgE and defective neutrophil motility were treated with a single oral daily dose of 1 g sodium ascorbate as a supplement to prophylactic trimethoprim- sulphamethoxazole therapy for 2 years. Laboratory tests of neutrophil functions were performed prior to ascorbate therapy and repeated at 1-monthly intervals for 6 months and at 6-monthly intervals thereafter. Introduction of ascorbate to the therapeutic regimen was accompanied by slight increases in neutrophil hexose monophosphate shunt activity and staphylocidal activity and good improvement of neutrophil motility in all three children. The improved staphylocidal activity was not due to ascorbate-mediated inhibition of neutrophil or serum catalase activities or to detectable increases in superoxide and H2O2 production or activity of the MPO/H2O2/halide system. Both male children have remained free from obvious infection since ascorbate was added to their therapeutic regimen; their sister has experienced one urinary tract infection during a period when treatment with prophylactic co-trimoxazole and ascorbate was inadvertently stopped. All three children have gained weight. PMID- 6265126 TI - Cardiac beta-adrenoreceptors in the thyroxine-treated dog. AB - 1. Myocardial beta-adrenoreceptors, assessed in membrane preparations of left ventricle by 3H-dihydroalprenolol binding, were compared in dogs following thyroxine administration (n = 6), aorto-caval fistula (n = 12), and in normal dogs (n = 7). 2. Left ventricular hypertrophy occurred in response to both aorto caval fistula and thyroxine treatment. Yield of myocardial membrane between the different groups was not significantly different. 3. Binding site concentration (pmol/mg membrane protein) in dogs with aorto-caval fistulae was similar to that in normal dogs and was not significantly influenced by the presence or absence of cardiac failure, degree of hypertrophy or duration of fistula. 4. Thyroxine treated dogs had an increased concentration of binding sites (c. 1.8-fold) compared with both fistula and normal groups, while binding affinities were similar in all groups. 5. The data suggest that beta-adrenoreceptor concentrations in myocardium increase as a direct result of thyroid hormone action rather than as a result of secondary haemodynamic changes or ventricular hypertrophy. PMID- 6265125 TI - The effects of GABA-ergic drugs on enkephalin-induced motor seizure phenomena in the rat. AB - 1. The relationship between the effects of GABA-ergic drugs and D-ala2-met enkephalinamide (DALA)-induced myoclonic contractions of inframandibular muscles has been studied in the rat. 2. GABA-ergic drugs altered enkephalin-induced myoclonic contractions in the following manner: (a) The GABA-mimetic drugs, muscimol, gabaculine and baclofen, decreased DALA-induced myoclonic contractions. (b) The GABA antagonist, bicuculline and the anticonvulsant substance, sodium valproate (dipropylacetic acid, DPA) potentiated DALA-induced myoclonic contractions. The potentiating effect of DPA is probably due to its opiate-like activity, since naloxone abolished this effect. 3. The modulatory effect of the GABA-mimetic drug on enkephalin-induced myoclonic contractions may give grounds for further study to test the possible use of other GABA-mimetic drugs and possibly opiate antagonists for the treatment of myoclonic syndromes. PMID- 6265127 TI - The effect of renal denervation on ACTH-induced hypertension in sheep. AB - 1. The effect of renal denervation on ACTH-induced hypertension in sheep has been examined. 2. Both intact and renally denervated sheep showed similar rises in blood pressure following ACTH treatment. 3. Following renal denervation, the initial urinary sodium retention and ACTH-withdrawal natriuresis typical of ACTH administration in intact sheep were absent, and the fall in blood pressure was delayed. PMID- 6265128 TI - The beta-adrenoreceptor in human lymphocytes. AB - The beta-adrenoreceptors of human lymphocytes were investigated by binding assays using a radiolabelled beta-adrenoreceptor agonist, 3H-hydroxybenzylisoproterenol, in an intact cell system. Intact human lymphocytes had binding sites for the ligand, which seemed to represent physiological beta-adrenoreceptors. Thus, assay of binding of the beta-adrenergic agonist, 3H-HBI, by intact lymphocytes can be used to study beta-adrenoreceptors in human tissue and to elucidate possible beta adrenoreceptor disorders in human diseases. PMID- 6265129 TI - The influence of heart rate on digoxin-induced inhibition of myocardial Na+-K+ ATPase activity in the dog. AB - 1. Groups of sedated dogs were studied at spontaneous heart rates (HR), 55 100/min, or at paced HR 200/min, with or without intravenous digoxin administration. After 60 min, active rubidium uptake (86 Rb+) of ventricular samples was determined in vitro. 2. Untreated fast and slow HR groups had similar uptakes. Following digoxin, 0.08 mg/kg, uptake was less at fast than slow HR (63.8, s.e.m. = 4.5 v. 87.5, s.e.m. = 5.0 pmol/mg LV/15 min, P less than 0.01). After 0.125 mg/kg, values were again lower in the fast HR group in which five of seven developed ventricular tachycardia. 3. Heart rate does not alter in vitro activity of myocardial Na+-K+-ATPase but does influence inhibition of the enzyme resulting from digoxin administration. PMID- 6265131 TI - Clinical trials with oral Futraful (INN: Tegafur) in cancer of the head and neck. PMID- 6265132 TI - [Demyelination of peripheral nerves]. PMID- 6265133 TI - [Peripheral nerve pathology of experimental lead neuropathy (author's transl)]. PMID- 6265130 TI - Age-related restriction of the light chain heterogeneity of anti-IgG antibodies induced by Epstein-Barr virus stimulation of human lymphocytes in vitro. PMID- 6265134 TI - [Asymmetrical evolution of demyelinating process in peripheral neuropathy; analysis on Guillain-Barre syndrome and experimental lead neuropathy (author's transl)]. PMID- 6265135 TI - Perinatal clostridium perfringens infection. PMID- 6265138 TI - Opposite effects of captopril on angiotensin I-converting enzyme 'activity' and 'concentration'; relation between enzyme inhibition and long-term blood pressure response. PMID- 6265137 TI - Activities of hexokinase, phosphofructokinase, fructose bisphosphatase and 2 oxoglutarate dehydrogenase in muscle of normal subjects and very ill surgical patients. AB - 1. The activities of hexokinase, phosphofructokinase, fructose bisphosphatase and 2-oxoglutarate dehydrogenase have been measured in the vastus lateralis and rectus abdominus muscle of normal human subjects and in very ill surgical patients. 2. The activities of these enzymes in the muscle of control subjects were similar to the pattern seen in the skeletal muscle of other mammals and lower vertebrates. 3. Fructose bisphosphatase and phosphofructokinase activities were significantly lower in the muscle of ill patients although the depression of the activity of fructose bisphosphatase was much greater than that of phosphofructokinase in both muscle types of ill patients. 4. The maximum rate of cycling in the fructose 6-phosphate--fructose, 1,6-diphosphate cycle may be altered in the ill. 5. This decreased cycling may have a direct influence on the sensitivity of glycolysis to regulators such as the adenine nucleotides and may reduce the ability to maintain body temperature. 6. Increased glycogen synthesis in these muscles may indicate that the role of fructose bisphosphatase is unlikely to be solely in glycogen resynthesis. PMID- 6265136 TI - Adrenergic facilitation by angiotensin: does it serve a physiological function? PMID- 6265139 TI - The effect of aging on beta-adrenoceptor-stimulated cyclic AMP formation in human lymphocytes. AB - 1. Responsiveness of the beta-adrenoceptor adenylate cyclase system was measured in lymphocytes from healthy young and old subjects by incubating the cells with isoprenaline in the presence of a phosphodiesterase inhibitor and by measuring production of adenosine 3':5'-cyclic monophosphate (cyclic AMP) with a competitive binding assay. 2. The two groups did not differ significantly in the levels of cyclic AMP produced or in the concentration of isoprenaline required to give half-maximal stimulation of the cells (ED50). PMID- 6265140 TI - Metabolism of antithrombin III in cirrhosis and carcinoma of the liver. AB - 1. The metabolism of human antithrombin III (ATIII) was studied by using 125I labelled tracer. 2. The plasma half-life (t0.5) was 2.71 +/- 0.26 days in normal subjects and was similar in patients with cirrhosis or primary carcinoma of liver. 3. Patients with cirrhosis had low ATIII levels, decreased intravascular mass, total body mass and decreased absolute catabolic rate, suggesting decreased synthesis. The positive correlation of ATIII level with fractional catabolic rate (K10) indicated that the decreased catabolic might exert a positive inhibition on ATIII production. 4. These abnormalities were more exaggerated in patients with macronodular cirrhosis associated with hepatitis surface antigen or in those with ascites. 5. In cirrhotic patients with ascites an additional extravascular pool of ATIII was present which did not turn over at the same rate as the intravascular pool. 6. Patients with primary carcinoma of liver had moderately low ATIII, but normal intravascular mass and total body mass because of the increased plasma volume and normal absolute catabolic rate. 7. The negative correlation of ATIII levels with K10 suggested that the low levels could be due to increased catabolism or consumption. 8. One patient with disseminated malignancy and active superficial thrombophlebitis had normal ATIII metabolism. PMID- 6265141 TI - Effect of propranolol therapy on aldosterone responses to angiotensin II and adrenocorticotropic hormone in essential hypertension. AB - 1. The plasma aldosterone responses to exogenous angiotensin II and adrenocorticotropic hormone (ACTH) were studied before and after 1 month of propranolol therapy (120-240 mg/day) in eight patients with essential hypertension. 2. Basal supine plasma renin activity was decreased (P less than 0.001) after propranolol, whereas plasma aldosterone was unchanged. After 3 h of upright posture the increases in both plasma renin activity and aldosterone were decreased (P less than 0.05) after propranolol. 3. Plasma aldosterone responses to exogenous angiotensin II and ACTH were not significantly different after propranolol. Serum and urinary electrolytes and plasma cortisol were also unaffected by propranolol therapy. 4. It is concluded that changes in adrenal sensitivity are not responsible for maintaining unchanged supine plasma aldosterone concentrations after beta-adrenoceptor antagonism in essential hypertension. PMID- 6265142 TI - Renal prostaglandins and water balance: studies in normal volunteer subjects and in patients with central diabetes insipidus. AB - 1. In six healthy volunteer subjects polydipsic water loading significantly increased urine volume from 1203 +/- 242 (SEM) to 5072 +/- 320 ml/24 h (P less than 0.001) with a significant decrease in urinary osmolality. This increase in urine volume by more than fourfold was associated with a slight increase in urinary excretion of prostaglandin E2 from 466 +/- 66 to 1017 +/- 174 pmol/24 h (P = 0.05). 2. In five patients with central diabetes insipidus mean urine volume of 10 838 +/- 107 ml/24 h was reduced to 1205 +/- 204 ml/24 h (P less than 0.001) by treatment with 1-desamino-8-arginine vasopressin (desamino-[Arg8]vasopressin; 15 microgram/day) with a significant rise in urinary osmolality. Desamino [Arg8]vasopressin treatment was associated with a significant increase of suppressed urinary excretion of prostaglandin E2 (PGE2) in four of these patients from 246 +/- 66 to 2643 +/- 677 pmol/24 h (P less than 0.01). 3. Concomitant treatment with indomethacin in addition to desamino-[Arg8]vasopressin significantly suppressed urinary excretion of PGE2 and significantly increased urinary osmolality as compared with treatment with desamino-[Arg8]vasopressin alone. 4. Desamino-[Arg8]vasopressin significantly increased urinary excretion of adenosine 3':5'-cyclic monophosphate (cyclic AMP). However, there was no further change in urinary excretion of cyclic AMP during concomitant indomethacin treatment. 5. The results suggest that urine flow itself is not an important determinant of urinary PGE2 excretion. In patients with central diabetes insipidus the urinary concentrating response to desamino-[Arg8]vasopressin is enhanced during inhibition of prostaglandin synthesis without changes in urinary excretion of cyclic AMP. PMID- 6265144 TI - Angiotensin-converting enzyme and pulmonary sarcoidosis. PMID- 6265143 TI - [Preliminary clinico-therapeutic trials of new cephalosporin: cefotaxime]. PMID- 6265146 TI - Bolus infusion CT enhancement as an aid in chemodectoma diagnosis-case report. AB - The boundaries of a carotid body chemodectoma are sharply defined by use of cranial computed tomography (CT) following the bolus infusion of intravenous iodinated contrast medium. The technique seems valuable in the preoperative staging of tumors in this locale. Enhancement strategies for CT imaging are discussed. PMID- 6265145 TI - Sugar residues on proteins. AB - Glycoproteins have become increasingly important in the structure and function of many different mammalian systems; for example, membrane glycoproteins and glycoprotein hormones. It is, therefore, important to understand their chemistry, which would include an understanding of both the carbohydrate and protein parts of the molecule. Since the chemical characterization of the protein moiety has been extensively examined and the techniques for its characterization are well worked out, only the carbohydrate portion of glycoproteins will be reviewed in this article. The chemical nature of the carbohydrate moiety of glycoproteins will be examined. First, the types of monosaccharides present in animal systems, especially those in the mammalian systems, will be described. Next, various types of simple and complex carbohydrate chains will be discussed to establish the diversity, size, and number of chains present in the carbohydrate units in different glycoproteins. Then, the type of linkages of the carbohydrate to the protein will be examined to determine if the primary sequence of protein is important in determining the size and type of carbohydrate chains present in glycoproteins. Finally, the current methods of structural elucidation such as monosaccharide sequence, intersugar bonds, and anomeric linkages in the carbohydrate moiety of glycoproteins will be reviewed. These methods include the techniques of periodate oxidation, methylation, partial acid hydrolysis, and specific glycosidase digestion of glycoproteins, as well as the latest techniques using micromethods of carbohydrate quantitation and characterization involving gas chromatography and mass spectrometry. The function of the carbohydrate in glycoproteins will also be considered. First, hormone glycoproteins will be discussed in their relationship to the immunological and biological function of the glycoprotein when the carbohydrate is sequentially removed. Next, the function of the carbohydrate in the turnover of glycoproteins will be discussed. These topics will be considered in order to develop an understanding of a specific function(s) of the carbohydrate in glycoproteins. PMID- 6265147 TI - Fiber as a binding agent. PMID- 6265149 TI - Occupational lung diseases. State of the art. PMID- 6265148 TI - Potential mechanisms of lung injury from hydroxyl radical. PMID- 6265151 TI - Pulmonary asbestosis and idiopathic pulmonary fibrosis: pathogenetic parallels. PMID- 6265150 TI - Isocyanate-induced abnormality of beta-adrenergic receptor function. PMID- 6265152 TI - Specific IgE antibodies in patients with isocyanate asthma. PMID- 6265153 TI - Alveolar macrophage stimulation and population changes in silica-exposed rats. PMID- 6265154 TI - Inhaling volcano ash. PMID- 6265155 TI - Risk assessment in volcano ash exposure. PMID- 6265157 TI - Hepatoma presenting as a single cavitary lung mass and leukemoid reaction. PMID- 6265156 TI - Chronic lung damage caused by adenovirus type 7: a ten-year follow-up study. AB - Twenty-seven children aged 0.6 to 7.0 (mean 2.1) years were admitted to the hospital in 1967 and 1968 with type 7 adenoviral pneumonia. All ran a prolonged course. Type 7 adenovirus was isolated from 14 children, and in the other 13, the rise in the titer of complement-fixing antibodies to adenovirus was fourfold or greater. The outcome of the disease in these 27 children was reassessed in 1979, 9.6 to 12.1 (mean 10.7) years after the adenovirus type 7 pneumonia. Twenty-two were examined clinically and roentgenographically and all had lung function tests. Twelve had abnormal chest roentgenograms, and of these, six had bronchiectasis. Six of the ten children with normal chest x-ray films and ten of the 12 with abnormal chest roentgenograms had abnormal pulmonary function tests. Of the six patients with bronchiectasis, four showed no discernible cause of bronchiectasis other than the antecedent type 7 adenoviral infection. The other two patients had bronchial asthma, which can be a risk factor for bronchiectasis. PMID- 6265158 TI - Study of the in vitro activity of new cephalosporins on strains of Neisseria gonorrhoeae of the Toulouse region. AB - The study was carried out with 50 strains of gonococci. Susceptibility to the antibiotics was determined by standard sensitivity test, by systematic test for beta-lactamase and by measurement of the MICs. The cephalosporins tested were: moxalactam, cefotaxime, ceftriaxone, cefotiam, cefoxitin, cefazolin and cephalothin. Their activities were also compared with other beta-lactams, namely penicillin and ampicillin. The efficacy in vitro of the cephalosporins: in the lead, ceftriaxone, remarkably active, with cefotaxime following very close, and then moxalactam with cefotiam a little behind, and finally all the other beta lactams tested. The median MICs of the new cephalosporins (moxalactam, cefotaxime, ceftriaxone and cefotiam) were at least 10 times greater than those of the other beta-lactams tested. The MIC values observed with a resistant strain (penicillin, ampicillin; MIC 256 microgram/ml) never exceed the maximum values found with the 50 susceptible strains. PMID- 6265160 TI - A case of malignant lymphoma, undifferentiated, Burkitt's type with high antibodies to Epstein-Barr virus. AB - A 5-year-4-month-old girl was admitted to Taipei Municipal Jen-Ai Hospital because of a rapidly enlarging right submandibular tumor. The diagnosis of malignant lymphoma, undifferentiated, Burkitt's type was made by distinctive histopathological features. Positive serological findings related to Epstein-Barr virus infection were disclosed. Complete remission has been achieved since the treatment with high-dose cyclophosphamide was given, and no signs of relapse have been found yet. PMID- 6265159 TI - Comparative in vitro activity of 8 cephalosporins on 109 strains of Neisseria gonorrhoeae and 60 strains of Neisseria meningitidis. AB - The in vitro activity of 8 cephalosporins - cephalothin, cefamandole, cefoxitin, cefuroxime, cefotaxime, cefoperazone, moxalactam and ceftriaxone (Rocephin) was studied on 109 strains of Neisseria gonorrhoeae and 60 strains of Neisseria meningitidis, isolated from pathological material. Determination of the MICs of these antibiotics by an agar dilution method shows that on N. gonorrhoeae ceftriaxone (geometric mean of the MICs: 0.0008 microgram/ml) is the most active, followed by cefotaxime (0.001 microgram/ml); cefoperazone (0.008 microgram/ml) and moxalactam (0.01 microgram/ml) are one-tenth as active; then come cefuroxime (0.05 microgram/ml), cefamandole (0.10 microgram/ml) and finally cephalothin (0.26 microgram/ml) and cefoxitin (0.26 microgram/ml). The least susceptibility to penicillin and, to a greater degree, the production of beta-lactamase (8 strains) affect the level of susceptibility to these cephalosporins, but the MICs always remain relatively low. PMID- 6265162 TI - [Systemic antibiotic prophylaxis in elective colon surgery. Results of a controlled study]. AB - A prospective controlled, randomized trial was carried out among 70 patients undergoing elective colonic surgery; 31 patients received a systemic prophylaxis with cefotaxime (3 h) before surgery for 4 days and 29 patients were controls. The large bowel preparation consisted of whole gut irrigation with 0.9% NaCl and Paromomycin 1 g/l. Both groups were well matched after randomization. The rate wound infections in the control group was 28% and, in the test group, 6.4% (p less than 0.05, chi2-test). A trend toward a lower rate of urinary tract infections, an astomosic dehiscences and septicemic complications was recognizable in the test group, but not significant. PMID- 6265161 TI - [Value and limitations of neurosecretory tests: the bromophenol blue test]. PMID- 6265164 TI - [Lithispermum eyedrops--anti-HSV experiment and clinical use (author's transl)]. PMID- 6265163 TI - Clinical chronopharmacology of ACTH-1 - 17. III. Effects on fatigue, oral temperature, heart rate, grip strength and bronchial patency. PMID- 6265165 TI - Brain stem mechanisms in the control of arterial pressure. AB - Electrical stimulation of a circumscribed region within the rostral part of the ventrolateral medulla elicits a large increase in arterial pressure accompanied by intense regional vasoconstriction. Microinjection of glutamate has established that the vasomotor effects are due to excitation of cell bodies rather than axons of passage within the ventrolateral region. Bilateral localized destruction of the same region results in a profound decrease in resting arterial pressure as well as virtual abolition of reflexes controlling sympathetic vasomotor activity. Neuroanatomical studies using the method of retrograde transport of horseradish peroxidase (HRP) have shown that this region contains a dense group of neurons projecting to the thoracolumbar spinal cord and receives major monosynaptic inputs from the nucleus tractus solitarius and parabrachial nucleus. There is some evidence that the spinally-projecting ventrolateral cells contain epinephrine. The anatomical and physiological evidence taken together indicate that the bulbospinal pathway originating from the ventrolateral cells plays a major role in the tonic and phasic regulation of arterial pressure. PMID- 6265166 TI - Importance of new catecholamine pathways in control of blood pressure. AB - The first comprehensive maps of central catecholamine pathways referred to both noradrenaline and dopamine neurons. They described the catecholamine neurons as having their cell bodies in the brainstem with spinal axons descending mainly from two medullary cell groups (A1 and A2) and with ascending axons arising mainly from more rostral groups (A3-A13). More recent work utilising immunohistochemistry has established the presence of adrenaline neurons in the brain, in two medullary cell groups (C1 and C2). While these were originally thought to lie within the rostral part of the A1 and A2 cell groups, work from this laboratory has now established that the adrenaline neurons are topographically distinct from the A1 and A2 cells, do not fluoresce with standard methods, and are collected into three groups, the third group (C3) lying in the midline of the rostral medulla. Work in this laboratory using a combination of histochemical fluorescence and retrograde transport of horseradish peroxidase has demonstrated that existence of a descending dopaminergic projection from the hypothalamus to the spinal cord, indicating that descending pathways can arise well above the medulla. Recent studies on the A1 neurons have established the presence of projections from the A1 cells to the median eminence of the hypothalamus and towards the nucleus tractus solitarius in the medulla. Other experiments have demonstrated that most of the descending catecholamine axons do not arise from the A1 and A2 cell groups in the caudal medulla, but higher up in the brainstem especially from the A5 and A7 cell groups. These new descriptions of central catecholamine neurons will necessarily modify the interpretation of many experiments on the central regulation of arterial pressure. PMID- 6265167 TI - Prostaglandin and angiotensin converting enzyme inhibition: effect on blood pressure, renin activity and renal function in hemorrhaged conscious rabbits. AB - The interaction of the prostaglandin and renin-angiotensin systems on blood pressure and renal function was studied in conscious rabbits following mild (6 ml/kg) or moderate (15 ml/kg) hemorrhage. One hour following the injection of the prostaglandin synthetase inhibitor indomethacin (Indo) plasma renin activity (PRA) was significantly lower than the values in control animals. Two hours following hemorrhage, the increase in PRA was very similar in the Indo and control animals. Renal plasma flow (RPF) was not affected by Indo. Glomerular filtration rate (GFR) was significantly lower in the Indo group following moderate hemorrhage. Interruption of the renin-angiotensin system with the converting enzyme inhibitor (CEI), captopril, resulted in similar hypotensive responses in the Indo and non-Indo groups. The marked PRA increase induced by this agent also was not influenced by Indo. The CEI increased RPF and decreased renal vascular resistance (RVR) in the mild hemorrhage animals. However, in the moderate hemorrhage group the RPF changes were variable and RVR tended to increase, especially in the Indo group. GFR fell significantly following captopril in both Indo and non-Indo animals after moderate hemorrhage. The results indicate that prostaglandin inhibition lowers basal PRA levels but that the renin response to hemorrhage and captopril are not prevented. Indo also did not alter the hypotensive response to CEI, suggesting that prostaglandins do not play a major role in this effect. The magnitude of the hemorrhagic stress influences the renal responses to inhibition of the prostaglandin or renin angiotensin systems in the conscious rabbit. PMID- 6265168 TI - Identification of a vasoactive substance (vasopressin) in a brain extract containing an unknown inhibitor of Na,K-ATPase. AB - An endogenous inhibitor of the Na,K pump, postulated to be involved in the etiology of some hypertensive states, has been reported in extracts of mammalian brain. This encouraged us to test its effects on arterial muscles. An acid acetone extract of guinea pig brain inhibited Na,K-ATPase derived from canine kidney and evoked responses in arterial strips similar to those produced by ouabain. Unlike ouabain, however, it did not prevent muscles in K-free solutions from relaxing when K was re-added. Bioassays on strips of arteries, uterus and portal vein indicated that the extract did not contain sufficient concentrations of norepinephrine, dopamine, serotonin, prostaglandins, angiotensin II, oxytocin or the Na,K-ATPase inhibitor to account for the observed vascular effects. This could not be said of vasopressin. Furthermore, vasopressin and the vasoactive component of the extract were equally sensitive to several peptidases, and conditions which cleave disulfide bridges. A radioimmunoassay verified that the extract contained sufficient vasopressin to cause contractions. Vasopressin did not inhibit the kidney Na,K-ATPase activity. Finally, the Na,K-ATPase inhibitor, but not the vasoactive substance, was present in extracts of vasopressin deficient Brattleboro rat brains. Therefore, the Na,K-ATPase inhibitor and the vasoactive substance in these extracts were distinctly different. PMID- 6265169 TI - Peripheral beta-adrenoceptor responsiveness in young normotensive and hypertensive subjects. AB - In young subjects with normal blood pressure (N = 10) or with mild (n = 6) or moderate (n = 8) hypertension we assessed the effects of increasing doses of i.v. isoproterenol (each dose for 10 min) on systolic and diastolic blood pressure, heart rate, plasma renin activity (PRA), serum potassium and free fatty acids (FFA). Except for blood pressure, basal levels did not differ significantly between the groups. Isoproterenol induced dose-related increases in systolic blood pressure, heart rate and PRA, and dose-related decreases in diastolic blood pressure. Neither the threshold dose (i.e. the lowest dose significantly affecting these parameters), nor the changes induced by the higher doses differed between the normotensive and hypertensive subjects. Levels of serum potassium and FFA, obtained at the end of the infusion, also did not differ significantly between the groups. These results indicate, that in contrast to older and/or more severely hypertensive subjects, young subjects with mild to moderate hypertension have a peripheral beta-adrenoceptor responsiveness similar to that of normotensive controls. PMID- 6265171 TI - Catechol estrogen formation in placental and fetal tissues of humans, macaques, rats and rabbits. AB - Placental and fetal tissues obtained from humans, monkeys, rats and rabbits contained monooxygenases capable of catalyzing the formation of catechol estrogens. Treatments of pregnant rats with phenobarbital, Aroclor 1254, or 3 methylcholanthrene each increased measured rates of catechol estrogen formation in placentas, fetal brains and fetal livers, while other rat tissues exhibited either increased or decreased activity. Treatment of pregnant rabbits with Arocolor 1254 produced an increase in catechol estrogen formation in all fetal tissues studied and in the maternal liver and kidney. Catechol estrogen formation in placental microsomes of macaque monkeys (Macaca arctoides) was generally less than that observed in human placental microsomes. Human placentas obtained from smokers exhibited enhanced catechol estrogen formation and this activity appeared to be highly correlated with placental aryl hydrocarbon hydroxylase activity. The data suggested [a]pyrene in a similar fashion in placental tissues and that the enzyme systems involved may be under similar regulatory control. PMID- 6265173 TI - Immunohistochemical characterization of histiocytic tumours. AB - Immunohistochemical labelling of histiocytic tumour cells in formalin-fixed paraffin-embedded material was usefully applied to malignant fibrous histiocytoma (MFH) and to malignant histiocytosis (MH). Not all cases of MFH showed a positive reaction, in contrast with the obligatory positive staining in MH. In general, histiocytic tumour cells stained more intensively with alpha 1-antichymotrypsin than with lysozyme. False positive results can be due to intermingled non neoplastic histiocytes or degenerating neoplastic cells in any mesenchymal tumour. PMID- 6265172 TI - Direct phosphorylation effects of epinephrine on the plasma membranes of intact rat fat cells. AB - Collagenase-treated isolated cells, prepared from epididymal fat pads of Sprague Dawley rats exposed to 32Pi or (gamma-32P)-ATP, result in differences in label incorporation into peptides as determined by autoradiography of dried SDS polyacrylamide gels. 32Pi-labelled cells respond to epinephrine by increase in labeling of a 67,000-dalton band, presumably the activated lipase. (gamma-32P) ATP exposed cells gave a dose-dependent increase in a 53,000-dalton band, a finding shared by cells exposed to cAMP in the absence of epinephrine. However, whereas, cAMP also significantly increased the labeling of an 18,000-dalton band, epinephrine had only a minor effect in the labeling of the 18,000-dalton component. Also, the degree of labeling of a 42,000-dalton band is diminished after epinephrine compared to unstimulated cells. By contrast, cAMP does not affect the labeling of the 42,000-dalton component. The localization of the 53,000- and the 18,000-dalton peptides as well as the enzyme(s) that catalyze their phosphorylation on the external surface of the fat cell is supported by studies using a number of macromolecular probes as well as by subcellular fractionation studies. The absence of such phosphopeptides or kinase activity in the infranatants of such cell suspensions eliminates the possibility that these phenomena are the result of leakage of cytoplasmic components. Thus, epinephrine appears to have effect and do not appear to be explicable simply by the release of cAMP to the extracellular compartment. PMID- 6265170 TI - Effects of octapeptide-cholecystokinin, secretin, and glucagon on intestinal mucosal growth in parenterally nourished rats. AB - Nutrients in the lumen of the small intestine may cause the release of enteric hormones which directly or indirectly stimulate intestinal mucosal growth. Male Sprague-Dawley rats with either an intact small bowel or following jejunal resection were maintained on total parenteral nutrition (TPN). C-terminal octapeptide-cholecystokinin alone or combined with secretin, or glucagon alone were added to the intravenous nutrient solution and continuously infused. Control rats received only TPN or gastric infusion of isocaloric amounts of TPN solution. After 7 days, intestinal hypoplasia was noted in rats with an intact bowel maintained on TPN alone compared with the gastrically infused group. TPN did not maintain the proximal-distal gradient of mucosal mass. Continuous intravenous infusion of octapeptide-cholecystokinin alone and together with secretin in rats maintained on TPN significantly stimulated small bowel mucosal growth, partially restoring the proximal-distal gradient. Glucagon infusion did not stimulate mucosal growth. Rats with a jejunal resection and maintained on TPN for 7 or 14 days failed to develop mucosal hyperplasia of the ileum in contrast to rats given the TPN solution intragastrically. Continuous intravenous infusion of octapeptide cholecystokinin in rats maintained on TPN after jejunal resection caused significant mucosal growth in the ileum compared with the rats maintained on TPN alone, but not to the extent seen in gastrically fed animals. Intravenous infusion of octapeptide-cholecystokinin stimulates small-bowel mucosal growth. Secretin appears to have an additional effect when given together with octapeptide-CCK. Although a direct trophic action by these hormones on the intestinal mucosa is possible, this effect is more likely mediated via stimulation of pancreaticobiliary secretions. PMID- 6265175 TI - [Properties of separate molecular forms of rat brain phosphoprotein phosphatase and their protein regulators]. PMID- 6265174 TI - The collagen prolyl hydroxylase activity of hepatocytes and mesenchymal cells isolated from normal and regenerating rat liver. AB - Prolyl hydroxylase activity has been demonstrated in separate populations of hepatocytes and mesenchymal cells from normal rat liver, the amount in the mesenchymal cell preparation being about twice that found in an equal number of hepatocytes. At the third day after partial hepatectomy, there is a 2- to 3-fold rise in hepatocyte prolyl hydroxylase and a 5-fold rise in the mesenchymal cell enzyme content. Sham operation causes a less striking elevation of prolyl hydroxylase in the mesenchymal cell preparations and has no effect on the hepatocyte enzyme. PMID- 6265176 TI - [Reversible structural changes in proteolyzed chromatin core-particles]. PMID- 6265177 TI - [Use of transition state theory for describing the potential dependence of the process of inactivation of rapid potassium current in molluscan neurons]. PMID- 6265178 TI - [Na, K+-ATPase regulation in neuroblastoma C1300 L cells and their membrane mutants depending on the culture growth stage]. PMID- 6265179 TI - [cAMP participation in the light regulation of carotenoid synthesis in Neurospora crassa]. PMID- 6265180 TI - [Proton receptor, a possible mechanism of pain sensitivity]. PMID- 6265182 TI - [Integration of the genomes of the tick-borne encephalitis virus and of the cell in chronic infection due to this virus and SV40]. PMID- 6265181 TI - [Changes in presynaptic potentiation and depression in the variation of the potassium component of the endplate current]. PMID- 6265183 TI - [Presence of "reserve" Na-K-ATPase molecules in cell membranes]. PMID- 6265184 TI - [Factor facilitating complete translation of the encephalomyocarditis virus genome]. PMID- 6265185 TI - [Receptor-specific antibodies in the genesis of Basedow's disease]. PMID- 6265186 TI - Unusual presentations of hepatoma in Ethiopians. PMID- 6265187 TI - [Effect of aldosterone on the metabolic quotient of (Na+, K+)-dependent adenosine triphosphatase from the rat brain and kidney]. AB - The authors examined the metabolic number of the enzyme (Na+, K+)-dependent adenosintriphosphatase (EK 3.6.1.3) in adrenalectomized, intact and chronically treated with aldosterone adrenalectomized animals. They accepted the amount of hydrolized ATF/one combining site for an unit of time as a metabolic number. They found that adrenalectomy lowered the specific enzymic activity in renal tissue and did not alter in the brain tissue. Aldosterone, administered intraperitoneally, in a dose of 10 mg per 100 mg of body weight daily for a period of 5 days, increased the specific enzymic activity in the examined both tissues. The metabolic number of the enzyme diminished after adrenalectomy in the brain and kidney and increased over the level of the control animals after administration of aldosterone. PMID- 6265188 TI - Gonadotropin-binding sites in the rhesus monkey ovary: role of the vasculature in the selective distribution of human chorionic gonadotropin to the preovulatory follicle. AB - These experiments were initiated to determine if differences exist in the vasculature of individual follicles in the rhesus monkey ovary during the late follicular phase of the menstrual cycle and to determine whether differences in vascularity result in differential exposure of certain follicles to gonadotropic hormones. The density of blood vessels within the thecal layer of the dominant follicle and other antral follicles was determined in ovaries from four animals removed on day 9 or 10 of the menstrual cycle. Blood vessels were identified using a histochemical stain for hemoglobin. Morphometric analysis indicated that the percentage of the thecal layer occupied by blood vessels in the dominant follicles (48%) was significantly greater (P less than 0.005) than that of other smaller antral follicles either within the same ovary as the dominant follicle (24%) or in the contralateral ovary (26%). To determine if differences in vascularity result in a differential supply of gonadotropins to the dominant follicle, we studied, by autoradiography, the in vivo and in vitro binding of [125I]hCG in four rhesus monkeys on day 9 of the menstrual cycle. Results of in vitro binding studies indicated that the thecal layer of virtually every antral follicle possessed hCG-binding sites. However, when [125I]hcg was injected iv into animals and allowed to distribute via the vasculature, the dominant follicle was heavily labeled while other smaller antral follicles accumulated little, if any, radioiodinated hCG. These observations indicate that increased vascularization of individual follicles results in preferential delivery of gonadotropins, and suggest that blood flow to individual follicles may play an instrumental role in the selective maturation of the preovulatory follicle in the rhesus monkey. PMID- 6265189 TI - Evidence that a serotonergic mechanism stimulates the secretion of pituitary beta endorphin-like immunoreactivity in the rat. AB - A pharmacological approach was used to investigate serotonergic control of the secretion of pituitary beta-endorphin-like immunoreactivity (beta-END-LI) in the rat. The administration of 75 or 200 mg/kg L-tryptophan (ip, over 30 min) increased brain serotonin by 17% and 19%, respectively, and increased circulating beta-END-LI from 0.30 +/- .06 to 0.56 +/- 0.7 and 0.64 +/- 0.8 ng/ml, respectively. D,L,5-Hydroxytryptophan (30 mg/kg, ip, over 30 min) produced a 4.9 fold increase in brain serotonin content and a 3.4-fold rise in plasma beta-END LI. The administration of a serotonin reuptake blocker, fluoxetine (10 mg/kg, ip, over 15 min), elevated basal levels of plasma beta-END-LI from a control value of 0.38 +/- 0.02 to 1.21 +/- 0.32 ng/ml. Exposure to ether increased circulating beta-END-LI to 1.08 +/- 0.18 ng/ml, and fluoxetine treatment further increased this rise to 1.69 +/- 0.09 ng/ml (P less than 0.05). Quipazine, a serotonin receptor agonist, evoked a dose-related (2.5-5.0 mg/kg, ip) increase in circulating beta-END-LI levels by 15-45 min post injection. By contrast, intraventricular injection of the neurotoxin 5,7-dihydroxytryptamine (75 microgram free base, for 10 days) caused a 77% depletion of brain serotonin and attenuated the rise in beta-END-LI levels in response to immobilization (3.28 +/- 0.20 vs. 1.83 +/- 0.25 ng/ml). A higher dose of 5,7-dihydroxytryptamine (200 microgram free base, for 10 days) significantly decreased resting levels of beta END-LI from 0.65 +/- 0.14 to 0.36 +/- 0.08 ng/ml. We conclude that brain serotonin neurons exert a stimulatory influence over the basal secretion of pituitary beta-END-LI and mediate, in part, the stress-induced release of this hormone. PMID- 6265190 TI - Stimulation of phospholipid labeling and steroidogenesis by luteinizing hormone in isolated bovine luteal cells. AB - The present study was conducted to examine the effect of LH on phospholipid metabolism in corpora luteal tissue. Collagenase-dispersed cells obtained from bovine corpora lutea of early pregnancy were incubated with 32PO4 in the presence or absence of LH and examined for their ability to incorporate this label into phospholipids. LH (1 microgram/ml) significantly increased 32P incorporation into total lipid extracts, with a time course similar to that of progesterone synthesis. This stimulation of 32P incorporation was dependent on the concentrations of LH, and this dose-response relationship correlated well with the dose response of LH-induced progesterone production. Bovine serum albumin and ACTH had no apparent effect on 32P incorporation into phospholipids or progesterone production. Separation of luteal cell phospholipid extracts by thin layer chromatography revealed that LH stimulated the incorporation 32PO4, mainly into phosphatidic acid and phosphatidylinositol, with small increases occurring in the polyphosphoinositide fraction. The LH-induced labeling of these individual phospholipids also appeared to be temporally and dose-related to the LH-induced increases in progesterone synthesis. LH had no effect on the labeling of phosphatidylcholine, phosphatidylserine, sphingomyelin, or cardiolipin. These results indicate that LH has selective effects on phospholipid metabolism in bovine luteal cells which may be a part of the mechanism of action of LH on steroidogenesis. PMID- 6265192 TI - Regulation of luteinizing-hormone-receptors and steroidogenesis in the neonatal rat testis. PMID- 6265191 TI - Induction and maintenance of gonadotropin and lactogen receptors in hypoprolactinemic rats. AB - The effect of 2-bromo-alpha-ergocriptine (BR)-induced hypoprolactinemia on the induction and maintenance of testicular gonadotropin and lactogen receptors was studied in 60-day-old rats after receptor regulation by a gonadotropin-releasing hormone agonist analog [[D-Ser-(tBu)6]des-Gly10-GnRH N-ethylamide (GnRH-A)] and in young animals during sexual maturation. In adult animals, BR treatment delayed the reappearance of LH binding in the testis after GnRH-A injection, but had no effect on the recovery of lactogen binding. BR treatment also inhibited the increase of LH binding that occurred in control animals during the experimental period, but did not affect lactogen binding. Furthermore, BR potentiated the effect of GnRH-A on the decrease of Leydig cell testosterone synthesis observed 2 days later in vitro. Eight days after GnRH-A injection, concomitant BR treatment significantly inhibited the recovery of Leydig cell cAMP production. In peripubertal (25- to 46-day-old) animals, BR diminished the normal rise in testicular LH receptors, but did not affect the increase in lactogen receptors. Serum testosterone levels and other features of pubertal development, such as balano-preputial separation and spermatogenesis, were unaffected by hypoprolactinemia. In neonatal female animals, significant lactogen binding was detected at 3 days of age, whereas hCG binding was not demonstrable until 9 days after birth. These findings indicate that the expression of lactogen receptors precedes that of LH receptors in the developing gonad, and that the increase of LH binding in the testis during pubertal development requires normal circulating PRL levels. In adult animals, hypoprolactinemia potentiates GnRH-A-induced desensitization of steroidogenesis and cAMP formation, as well as LH receptor down-regulation, delaying the recovery of these phenomena. Although decreased serum PRL levels were associated with a marked reduction in testicular LH receptors both during development and in adult life, the absence of changes in lactogen receptors indicates that the latter sites are largely independent of the circulating PRL concentration. PMID- 6265193 TI - Insulin release from the isolated perfused rat pancreas containing insulinomata induced by streptozotocin and nicotinamide: effects of glucose and responses to tumor removal. AB - The kinetics of insulin secretion in response to glucose were studied in the in vitro perfused rat pancreas before and after removal of islet cell tumors induced by streptozotocin and nicotinamide. In addition, insulin secretion before and after tumor removal was compared with that from normal pancreata before and after sham operations, respectively. Thus, the two pancreas preparations were subjected to repeated perfusions with glucose. Perfusion of pancreata containing tumors with 8.4 mM glucose resulted in biphasic release in a pattern similar to that of normal pancreas. However, both basal and stimulated insulin secretion of tumor bearing pancreata were greater than either those of pancreata from which tumors had been excluded by ligature or those of normal pancreata before sham operation. A second increase in the concentration of glucose from 2.8 to 8.4 mM also produced a biphasic release of insulin from extratumoral pancreata as well as from sham-operated normal pancreata. However, the insulin secretory response to glucose of extratumoral pancreatic tissue was less than that of control pancreatic tissue. Our findings indicate that pancreatic islet cell tumors induced by streptozotocin and nicotinamide respond to glucose with typical biphasic insulin release. Thus, chemically induced rat insulinomata may provide a readily available and valuable model of insulin-secreting tissue, analogous to normal islets. Furthermore, our study suggests that the B cell function of pancreata containing tumors is inhibited by the preexisting tumor-induced hyperinsulinism or by its metabolic consequences. PMID- 6265194 TI - Isolation of purified rat Leydig cells using continuous Percoll gradients. AB - Continuous, isoosmotic Percoll gradients were utilized to isolate highly purified (90-95%) Leydig cells from rat testicular interstitial cell suspensions. The purified Leydig cells were contained in the third of four bands generated on the gradient, and retained their morphological and biochemical integrity. The cells in the purified Leydig cell fraction stained positively for 3 beta-hydroxysteroid dehydrogenase activity, appeared characteristic of steroid synthesizing cells when examined electron microscopically, specifically bound 125I-hCG and responded to hCG stimulation in vitro by producing testosterone. This procedure for isolating purified Leydig cells has advantages over methods currently in use as the gradients are essentially isoosmotic throughout, are easily generated, relatively inexpensive to use, and are readily applicable to sterile procedures when cell culture is anticipated. PMID- 6265195 TI - [New theories on the mechanism of follitropin action in the male gonad (review of the literature)]. PMID- 6265196 TI - [Insulin, gastrin, cyclic AMP, free fatty acids and pyruvates in the blood of children of diabetic families after oral administration of glucose, diabetol, aminoacids and fats]. PMID- 6265197 TI - Raben lecture 1980: a tale of stature. PMID- 6265198 TI - Biogenic amines and the secretion of parathyroid hormone and calcitonin. PMID- 6265199 TI - Control of adrenal androgen secretion. PMID- 6265201 TI - Commentary. PMID- 6265202 TI - Lung cyclic 3',5'-adenosine monophosphate and adenylate cyclase in endotoxic shock. AB - Cyclic 3',5'-adenosine monophosphate (cyclic AMP) and adenylate cyclase activity were measured in lungs from guinea pigs in endotoxic shock induced by an intravenous injection of Salmonella enteritidis endotoxin (10 mg/kg body weight). Both cyclic AMP content and adenylate cyclase activity were significantly elevated in lung tissue from the endotoxic guinea pigs. There was no apparent change in the affinity of adenylate cyclase for its substrate (ATP); however, the maximum velocity of the enzyme reaction was increased in lungs from the endotoxic group. Endotoxin, in the concentration range of 10(-4) to 10(-2) micrograms/ml, added to lung homogenates did not affect adenylate cyclase activity. Prostaglandins do not seem to mediate the effects of endotoxin in vivo on lung cyclic AMP since treatment of guinea pigs with indomethacin (10 mg/kg body weight) 30 min prior to endotoxin administration did not alter the endotoxin induced increase in lung cyclic AMP. PMID- 6265200 TI - Hypertension of childhood with suppressed renin. PMID- 6265203 TI - The liver-protective enzymes against reduced forms of oxygen in phenobarbital treated rats. AB - It is well known that phenobarbital treatment increases the production of superoxide anion by liver microsomes. Since the toxicity of superoxide anion and of its product, hydrogen peroxide, is well documented we measured the activities of the liver enzymes which protect the cell against the reduced forms of oxygen and the microsomal content of lipoperoxides in phenobarbital-treated rats. It was found that no lipoperoxides accumulate in the microsomes and that glutathione peroxidase, glutathione reductase activities, and the peroxidative activity of cytochrome P-450 were increased while catalase and superoxide dismutase activities were not modified. PMID- 6265204 TI - Brain phosphorylation and decarboxylation of mevalonic acid in the neonatal chick. AB - The three enzymes which catalyze mevalonic acid (MVA) phosphorylation and decarboxylation in neonatal chick brain are essentially located in the soluble fraction. The specific activity of pyrophosphomevalonate decarboxylase was the lowest of the three mevalonate-metabolizing enzymes. The rate of MVA phosphorylation and decarboxylation as a function of MVA concentration was studied. The apparent Km value of mevalonate kinase for MVA was 255 mumol/l. All three enzymes in chick brain showed a specific requirement for ATP for optimal activity. The effect of different Mg2+ concentrations was also studied. Mevalonate kinase and phosphomevalonate kinase showed maximal activity at pH 9.2 whereas pyrophosphomevalonate decarboxylase activity was highest at about pH 6.5- 6.7. PMID- 6265205 TI - Metabolic implications of ageing: changes in activities of key lipogenic and gluconeogenic enzymes in the aged rat liver. AB - The variations in enzyme activities involved in the main pathways of liver energetic metabolism--glycolysis, Krebs cycle, gluconeogenesis and lipogenesis- have been studied in rats ranging between the age of 4 days and 21 months. The major changes observed are the following: (1) enzymes involved in glycolysis (pyruvate kinase) and lipogenesis (NADP-malic enzyme, ATP-citrate lyase) decrease in activity during ageing, and (2) gluconeogenic enzymes (phosphoenolpyruvate carboxykinase, glucose-6-phosphatase) are maintained or slightly increased over the same period. The results suggest that an increase in the capacity for gluconeogenesis with respect to that for lipogenesis takes place in the aged rat liver. PMID- 6265206 TI - Transmission of equine infectious anaemia virus from a horse negative to agar gel immunodiffusion testing. PMID- 6265207 TI - Endotoxaemia in the horse. AB - Endotoxins are non-protein fragments of the cell wall of Gram-negative bacteria. They must be absorbed into the circulation to produce disease and systemic effects are similar, regardless of bacterial source. Absorption of endotoxins occurs in obstructive bowel disease and may play a significant part in determining the severity of the disease. Many of the responses to experimentally administered endotoxin are identical to those of bowel diseases or the horse and include circulatory, haematological and metabolic alterations. Therapeutic approaches are indirect and include many drugs currently employed in equine practice. The agents are directed toward mediators of the disease rather than the endotoxins themselves and include fluids, corticosteroids, anti-inflammatory drugs, energy sources and vasoactive drugs. The rationale for use and dosages are discussed. PMID- 6265208 TI - Nucleotide sequence coding for the respiratory NADH dehydrogenase of Escherichia coli. UUG initiation codon. AB - The nucleotide sequence of the structural gene coding for the respiratory NADH dehydrogenase of Escherichia coli has been determined by the chain-termination method. The reading frame for the protein starts with the unusual initiation codon UUG and predicts an amino acid sequence of 434 residues (Mr = 47 304). The reading frame was confirmed by protein chemical studies including determination of the N-terminal sequence of the protein. The product made in vivo was found to have threonine as its N-terminal residue, indicating that the initiating N formylmethionine had been removed by post-translational processing. PMID- 6265209 TI - On the molecular and submolecular structure of the semiquinone cations of alloxazines and isoalloxazines as revealed by electron-paramagnetic-resonance spectroscopy. AB - The thermodynamically stable and, therefore, analytically most important alloxazine and isoalloxazine radical cations have been studied in detail by electron paramagnetic resonance (EPR) spectroscopy. Isotopic and chemical substitutions have been made as in earlier studies with the less stable neutral and anionic species. The experimental spectra have been calculated with the aid of a more sophisticated computer-simulation program than previously used. Excellent fits were obtained only when all of the following atoms were taken into account in the hyperfine coupling scheme: N-5 H, N-10 H or CH3, C-6 H, C-7 H, C-8 H or CH3 and C-9 H. An additional but small coupling constant was required for the fit. This latter coupling constant is assigned to the nitrogen atom(s) of the pyrimidine subnucleus of (iso)alloxazine radical cations. The EPR-active proton is attached to N-5 as we also found for the neutral flavosemiquinone. The alloxazine and isoalloxazine radical cations exhibit an identical hyperfine coupling scheme but differ especially in the pyrazine nucleus with respect to the spin density distribution. This suggests that the geometrical structure of the two kinds of radicals is somewhat different. The highest spin density is, however, located at N-5 of (iso)alloxazine as has been found for the other flavosemiquinone species. The hyperfine coupling constants are interpreted in terms of spin densities and comparison is made with the most recently available quantum chemical calculations. All monomeric flavosemiquinone species are compared with each other and their differences in the submolecular structure are discussed briefly. PMID- 6265210 TI - Membrane-bound and water-soluble cytochrome c1 from Neurospora mitochondria. AB - Cytochrome c1 is a subunit of ubiquinol--cytochrome c reductase (EC 1.10.2.2). In Neurospora crassa wild type 74A grown in the presence of chloramphenicol, the subunit is inserted only into the bilayer of the mitochondrial inner membranes without associating with other proteins. From these modified membranes a monodisperse (cytochrome c1)-Triton complex was isolated by subjecting the Triton solubilized membranes to affinity chromatography on immobilized cytochrome c. A water-soluble pentamer of cytochrome c1 was prepared from the (cytochrome c1) Triton complex by removing the detergent. By limited proteolytic digestion of the cytochrome c1-Triton complex with chymotrypsin, a water-soluble monomeric cytochrome c1 was prepared which has a molecular weight of only 24 000 as compared to 31 000 of the membrane-bound cytochrome c1. The 24 000-Mr cytochrome c1 and the 31 000-Mr cytochrome c1 have same light absorption spectra and cytochrome-c-binding properties. These results are used to propose the following model. Cytochrome c1 consists of a large hydrophilic part and a small hydrophobic part. The hydrophilic part extends from the mitochondrial inner membrane into the intermembrane space. This part carries the heme and interacts with cytochrome c. The hydrophobic part anchors the cytochrome c1 to the bilayer. PMID- 6265211 TI - Isomers in thioredoxins of spinach chloroplasts. AB - We have developed a method for the concomitant purification of several components of the ferredoxin/thioredoxin system of spinach chloroplasts. By applying this method to spinach-leaf extract or spinach-chloroplast extract we separated and purified three thioredoxins indigenous to chloroplasts. The three thioredoxins, when reduced, will activate certain chloroplast enzymes such as fructose-1,6 bisphosphatase and NADP-dependent malate dehydrogenase. Fructose-1,6 bisphosphatase is activated by thioredoxin f exclusively. Malate dehydrogenase is activated by thioredoxin mb and thioredoxin mc in a similar way, and it is also activated by thioredoxin f but with different kinetics. All three thioredoxins have very similar relative molecular masses of about 12,000 but distinct isoelectric points of 6.1 (thioredoxin f), 5.2 (thioredoxin mb) and 5.0 (thioredoxin mc). The amino acid composition as well as the C-terminal and N terminal sequences have been determined for each thioredoxin. Thioredoxin f exhibits clear differences in amino acid composition and terminal sequences when compared with the m-type thioredoxins. Thioredoxin mb and thioredoxin mc, however, are very similar, the only difference being an additional lysine residue at the N-terminus of thioredoxin mb. Amino acid analyses, terminal sequences, immunological tests and the activation properties of the thioredoxins support our conclusion that thioredoxins mb and mc are N-terminal redundant isomers coming from one gene whereas thioredoxin f is a different protein coded by a different gene. PMID- 6265212 TI - Reactivation of the phospho form of the NAD-dependent glutamate dehydrogenase by a yeast protein phosphatase. AB - A protein phosphatase was isolated from the yeast, Candida utilis, which could reactivate (dephosphorylate) the phosphorylated form of the NAD-dependent glutamate dehydrogenase. The protein could also dephosphorylate casein, histone and kemptide (a heptapeptide corresponding to the phosphorylation site of liver pyruvate kinase). Reactivation of the phosphorylated glutamate dehydrogenase was stimulated by the simultaneous addition of NAD and L-glutamate; 2-oxoglutarate, NH+4 and NADH had no effect. The reactivation of phosphorylated glutamate dehydrogenase could be inhibited by phosphate, pyrophosphate and fluoride. PMID- 6265213 TI - The influence of elongation-factor-Tu . GTP and anticodon-anticodon interactions on the anticodon loop conformation of yeast tRNATyr. AB - The interactions of yeast tRNATyr, spin-labelled at position i6A-37 next to the anticodon, with EF-Tu . GTP and with Escherichia coli tRNAVal (which has a complementary anticodon) have been studied. The immobilization of the spin label upon ternary complex formation shows a conformational change of the anticodon region, although this part of tRNATyr is not in direct contact with the protein, as indicated by RNase T1 digestion. Upon anticodon-anticodon interaction, no conformational change of the anticodon loop of tRNATyr was observed. PMID- 6265214 TI - Demonstration of a heterogenous population of binding sites for thyroliberin in prolactin-producing tumour cells and their possible functional significance. PMID- 6265215 TI - The state of actin in activated human platelets. AB - The state of platelet actin was determined using a fluorescent method of DNAse I inhibition. Activation of human platelets resulted in mobilization of DNAse available actin. When platelets were activated with ADP the change in the state of actin was gradual and preceded the secretion. When thrombin was used as an activator, a sharp and rapid decrease in the DNAse-available actin was observed which paralleled the secretion. Inhibition of ADP-induced aggregation (and secretion) by EDTA resulted in a decrease in the rate of change on actin. Inhibition of the thrombin-induced aggregation (but not secretion) by EDTA did not affect the change in the state of actin. PMID- 6265216 TI - ADP-ribosylation of proteins in non-infected Escherichia coli cells. AB - Partially purified enzymatic fractions from extracts of Escherichia coli B/r catalyse transfer of the isotope label from [adenine-2,8-(3)H]NAD+ to some bacterial proteins, as well as to hen egg-white lysozyme. The radioactive group in the modified lysozyme was identified as mono(ADP-ribose). Several bacterial proteins were labelled in vivo with 32P; the presence of the label in the form of an ADP-ribosyl group was shown in one of them. PMID- 6265217 TI - The effect of parathyroid hormone on technetium-99m pyrophosphate distribution in rats. PMID- 6265219 TI - Changes in 86-rubidium uptake in erythrocytes of digoxin-treated patients, in heart failure with sinus rhythm. Relationship to clinical effects. AB - Previous studies have shown a significant relationship between the clinical effect of digoxin and a tissue response, namely the inhibition of 86Rb uptake by the patients' erythrocytes. In the present study, this relationship is confirmed in patients, in heart failure with sinus rhythm. The slowing of the heart rate but not the QS2 index changes correlates significantly with the 86Rb uptake inhibition. PMID- 6265218 TI - Point by Point Examination of the equilibrium gated radionuclide left ventricular time activity curve; validation by biplane angiography. AB - Examination of the time course of left ventricular ejection has been found useful in several clinical applications. Equilibrium gated radionuclide angiography provides non-invasive means to obtain the ventricular ejection curve. To evaluate the accuracy of the equilibrium gated radionuclide left ventricular volume curve we compared equilibrium gated radionuclide date with biplane cine-angiography in 16 patients examining each set of data on a point by point basis. The cine angiographic data consisted of 60 frame per second biplane cineangiograms and the radionuclide data consisted of 28 points spanning the cardiac cycle. All data was normalized for the patient's heart rate and stroke volume. The equilibrium gated radionuclide angiographic data accurately reproduced the contrast angiographic data at each point on the curve. This result justifies using the equilibrium gated radionuclide time activity curve to evaluate parameters such as early systolic ejection rates or rates of maximum ventricular ejection. PMID- 6265220 TI - Digoxin in the elderly and in renal failure. Contribution of erythrocyte 86 rubidium uptake tests. AB - Na+,K+-ATPase activity was assessed indirectly in three groups of subjects of differing age, and in a group of patients with renal failure, by measuring the 86 rubidium uptake in the patients' own erythrocytes. The inhibiting action of digoxin on this activity was also measured in vitro. Erythrocyte 86Rb uptake was found to be lower in the elderly as was the calculated volume of distribution of digoxin. Sensitivity to the inhibiting action of digoxin increased with age. In the renal failure group 86Rb uptake was diminished and the sensitivity to digoxin was variable. This suggested that Na+,K+-ATPase activity could be one determinant of the volume of distribution of digoxin and that quantitative and qualitative changes of this enzyme could explain features of the pharmacokinetics of digoxin in renal failure and in old age. PMID- 6265221 TI - Haemodynamic and metabolic effects of combined adrenergic alpha- and beta receptor blockade with labetalol in the exercising human forearm. AB - At rest supine acute intravenous administration of the combined adrenergic alpha- and beta-receptor blocking compound labetalol (1 mg/kg body weight) to young, healthy, male subjects, produced a clear-cut fall in arterial blood pressure. During dynamic forearm exercise, forearm blood flow decreased by 17.2%, and calculated vascular resistance increased by 11.3% after labetalol. Forearm oxygen uptake decreased (14.6%), suggesting an increased mechanical efficiency. Lactate release from the exercising forearm decreased (17.6%), probably because of the beta-receptor blockade. Forearm uptake of glucose and free fatty acids remained unchanged. Arterial blood glucose concentration attained a higher level after labetalol. Arterial plasma concentration of FFA was reduced during exercise and post-exercise probably because beta-receptor mediated lipolysis was antagonized. PMID- 6265222 TI - Effects of a standardized wheat bran preparation on biliary lipid composition and bile acid metabolism in young healthy males. AB - The effects of adding bran to the normal diet on biliary lipid composition and bile acid metabolism in a group of young healthy males was studied. A chemically standardized coarse wheat bran product, with serum lipid lowering properties, in a dose of 0.5 kg-1 body weight per day was used. Bran feeding for 4 or 8 weeks did not change biliary lipid and biliary bile acid composition. Faecal bile acid and neutral sterol composition was similar before and after 8 weeks of bran. Bile acid kinetics, measured by double isotope dilution after simultaneous injection of [3H]cholic acid and [14C]deoxycholic acid, showed only minor differences before and during bran ingestion. The most surprising finding was an increase in 7 alpha-dehydroxylation fraction (input of deoxycholic acid divided by synthesis of cholic acid) in six out of seven subjects after 4 weeks of brain and in all four subjects after 8 weeks of bran. In conclusion, the bran product we used is not effective in lowering the biliary cholesterol saturation in healthy young males. Nor does it reduce deoxycholate input in our subjects even after 8 weeks of bran. PMID- 6265224 TI - Effects of Pexid on liver cell cultures. Ultrastructural and histoenzymological studies. AB - The effects of different doses of Pexid on cultured liver cells have been studied by ultrastructural and histoenzymological techniques. Two types of abnormal lysosomal inclusions were seen: clear matrix inclusions with either homogeneous or tiny lamellar structures, and dark matrix inclusions with clear vacuoles and either random or myelin-like lamellar structures. These patterns correspond to storage of triglycerides, phospholipids and gangliosides, either singly or together. PMID- 6265223 TI - Interaction of desipramine and amitriptyline with adrenergic mechanisms in the human iris in vivo. AB - Mydriatic responses of the pupil were evoked by locally instilled noradrenaline and methoxamine in eight healthy volunteers. The effects of three single oral doses (25 mg, 50 mg and 100 mg) of amitriptyline and desipramine were compared on the mydriatic responses. Both antidepressants potentiated the mydriasis evoked by noradrenaline; desipramine appeared to be approximately four times more potent than amitriptyline. Both antidepressants antagonised the mydriasis evoked by noradrenaline; desipramine appeared to be approximately four times more potent than amitriptyline. Both antidepressants antagonised the mydriasis evoked by methoxamine, amitriptyline being approximately twice as potent as desipramine. It is suggested that the potentiation of the response to noradrenaline may reflect the blockade of the uptake of noradrenaline into adrenergic nerve terminals, whereas the antagonism of the response to methoxamine may reflect the blockade of postsynaptic alpha-adrenoceptors by the antidepressants. It is argued that the interaction of the antidepressants with adrenergic mechanisms could explain why amitriptyline, a potent anticholinergic agent, causes no significant change in resting pupil diameter, while desipramine, a relatively weaker anticholinergic agent, produces a significant mydriasis. PMID- 6265225 TI - Involvement of dopamine in circling responses to muscimol depends on intranigral site of injection. AB - The intensity, direction and dopamine dependence of circling behaviour were determined following stereotaxic injections of 40 ng muscimol (in 0.2 microliter over 3 min) into different regions of the rat's substantia nigra (SN). Weak, haloperidol-sensitive ipsilateral postural or locomotor asymmetries were invariably obtained from the rostral SN zona compacta (SNC), whilst robust contraversive rotational behaviour was always initiated from the SN zona reticulata (SNR) and caudal SNC. This was most rapid from the central SNR and was markedly attenuated by i.p. pretreatment with haloperidol (0.1 mg/kg) or pimozide (0.25 mg/kg), or by week-old 6-OHDA lesions of the nigrostriatal dopamine (DA) tract. Turning was significantly weaker from the lateral and ventral areas of the SNR, where it was not susceptible to DAergic blockade. Lower circling rates were also obtained if the SNR injections were made rapidly (in 30 sec), in a large volume (0.5 microliter) or at a supramaximal dose level (400 ng), possibly due to increased spread of the drug to remote neurones having an opposite effect on directional behaviour, or to exaggerated stereotypy. The variable action of muscimol at multiple sites in the SN is suggested to account for the earlier conflicting data in the literature. PMID- 6265227 TI - Comparison of the effects of beta-endorphin and morphine on exploratory and socio sexual behaviour in the male rat. AB - The socio-sexual and exploratory behaviour profiles were studied in male rats after intracerebral administration of beta-endorphin and morphine. Two social test situations were used, one with a sexually receptive female and one with a castrated male as the stimulus subject. Time (10-60 min)-response and dose (0.25 5.0 millimicron)-response relationships were investigated. A dose of 5 millimicron of beta-endorphin or morphine decreased exploratory activity and socio-sexual approaches. At lower doses (0.5-1.0 millimicron) beta-endorphin produced a more selective inhibitory effect on copulatory behaviour than morphine, which still caused a general depression of both social and sexual behaviours. In contrast to morphine, beta-endorphin increased amicable social contacts at a dose (1 millimicron) which decrease sexual responses. The dissimilarities in morphine and beta-endorphin effects suggest involvement of different brain areas or opiate receptors. The particular behaviour profiles observed after treatment with beta-endorphin indicate the possibility that beta endorphin influences mechanisms implicated in perception or interpretation of environmental stimuli. PMID- 6265226 TI - Relationship between inhibition of pressor response to angiotensin I and blood concentration of captopril following a single oral administration to dogs. AB - The time courses for the inhibition of the pressor response to AI and for the blood concentration of captopril and its metabolites were determined following a single oral administration of captopril at a dose of 0.8 or 2.5 mg/kg to normal dogs. Captopril was rapidly absorbed from the gastro-intestinal tract attaining a maximum blood concentration 1-1.5h after its administration. The inhibition of the pressor response to AI was closely related with the blood concentration of unchanged captopril but not of total captopril. The blood concentrations of captopril which produced 50 and 100% inhibition were estimated to be 0.1 and 0.4 millimicron/ml respectively. At 2.5 mh/kg the maximum blood concentration attained was 4 times higher than the concentration required to completely inhibit the pressor response to AI, suggesting that a fraction of the absorbed captopril was in excess of the therapeutic requirement. PMID- 6265229 TI - The hypothermic effect of clonidine and other imidazolidines in relation to their ability to enter the central nervous system in mice. AB - Clonidine and several other structurally related imidazolidines were administered intraperitoneally to mice and their capacity to cause hypothermia was used as an indication of their ability to enter the central nervous system. The substances were: clonidine (2-[w,6 dichlorophenylimino] imidazolidine) and its 2, 6 disubstituted derivates: St 91 (2,6-diethyl), St 93 (2-chloro, 6-methyl), St 95 (2,6-dimethyl) and St 1697 (2-ethyl, 6-methyl). All caused dose-dependent reductions in body temperature. Clonidine was most potent and was effective over the range 62.5-500 millimicron/kg i.p. clonidine lowered body temperature by 2.9 0.15oC. Relative potencies (R) were: clonidine (R 1), St 91 (0.41), St 1697 (0.29), St 93 (0.21) and St 95 (0.06). Hypothermia was inhibited by piperoxan injected intracisternally (10 millimicron/kg) but not intraperitoneally (10 and 50 millimicron/kg). Following intracisternal administration, the imidazolidine dose response curves were shifted in a parallel fashion to the left relative to the intraperitoneal administration. It is suggested that these compounds can all cross the blood-brain barrier in mice and interact with central alpha adrenoceptors to cause hypothermia. These findings are at variance with the abilities of some of these substances to cause sedation and hypotension mediated by interaction with central alpha-adrenoceptors. PMID- 6265230 TI - Prostacyclin prevents ischemia-induced increase of lactate and cyclic AMP in ischemic myocardium. AB - The effect of prostacyclin (PGI2, 0.5 nmol . kg-1 . min-1,i.v.) on myocardial metabolism was studied in cats subjected to 5 h of myocardial ischemia (MI) and compared to vehicle-treated MI cats. MI was followed by a 52% decrease in ATP and a concomitant increase (2-3 fold) in lactate and lactate/pyruvate ratio in the severely ischemic area. PGI2 prevented this increase in lactate with an unchanged ATP and lactate/pyruvate ratio. Moreover, PGI2 abolished the ischemia-induced in myocardial cAMP. It is concluded, the PGI2 exerts its beneficial actions on ischemic myocardium partly via cAMP-linked mechanisms. PMID- 6265228 TI - Relation between brain catecholamine receptors and dopaminergic stereotypy in rat strains. AB - In order to examine the potential relation between behaviour elicited by apomorphine and the density of catecholamine receptors, we studied stereotypy and the binding of [3H]spiperone to D2-(or neuroleptic/dopamine) receptors, of [3H]WB 4101 to alpha1-adrenoceptors, and [3H]clonidine to alpha2-adrenoceptors in two strains of rats. The F344 rats exhibited significantly more stereotypy to apomorphine than the Buffalo strain of rats. Other F344 rats which did not receive apomorphine and 34% more D2-receptors in the striatum and 50% more D2 receptors in the olfactory tubercle. Alpha2-Receptors in the frontal cortex were 20% higher in F344 rats when compared to the Buffalo strain, while alpha 1 receptors were the same across both strains. These results suggest a relation between D2-dopamine/neuroleptic receptor density and behavioural responsiveness to the direct-acting and specific dopamine agonist, apomorphine. PMID- 6265231 TI - An interaction between prejunctional alpha-adrenoceptors and prejunctional beta adrenoceptors. AB - The ability os isoprenaline to enhance transmitter release from sympathetic nerves in rat atria incubated with [3H]noradrenaline was assessed under three conditions of prejunctional alpha-adrenoceptor activation: in the presence of phentolamine, in the presence of noradrenaline, and in the absence of either drug. Isoprenaline-induced enhancement of transmitter release was inversely related to the degree of activation of prejunctional alpha-adrenoceptors. Thus there appears to be an interaction between the prejunctional alpha-adrenoceptor inhibitory mechanism and the prejunctional beta-adrenoceptor facilitatory mechanism. In rabbit ear arteries incubated with [3H]noradrenaline, isoprenaline facilitated transmitter release in the presence but not in the absence of phentolamine. Therefore in some tissues it may be necessary to block prejunctional alpha-adrenoceptors before prejunctional beta-adrenoceptors can be demonstrated. PMID- 6265232 TI - Dissociation of increases in cyclic GMP from relaxation of arterial smooth muscle. AB - Glyceryl trinitrate increased the cyclic GMP content of epinephrine-contracted aortic strips from glyceryl trinitrate-tolerant rats in a dose-dependent manner. Glyceryl trinitrate (.05 millimicron/ml) at a concentration that caused to relaxation of aortas from tolerant animals but a 42.4 3.7% relaxation of control aortas, elevated cyclic GMP levels in both groups approximately 3-fold. The results are not consistent with the hypothesis that cyclic GMP is involved in the relaxation of arterial smooth muscle. PMID- 6265233 TI - 3-hydroxymethyl-beta-carboline antagonizes some pharmacologic actions of diazepam. PMID- 6265234 TI - Effect of RP 30356 on the fast inward Na current in frog atrial fibres. AB - The effect of a new drug: RP 30356, on action potential and fast inward Na current of frog atrial fibres was studied using the double sucrose gap voltage clamp technique. The drug (10(-4)M) blocked the action potential without noticeably altering the resting membrane potential. RP 30356 inhibited the fast sodium conductance without changing the selectivity of the Na channel. The time to peak of the inward current was not significantly altered by the drug whereas the rate of the Na current inactivation pi h was slowed. The steady state inactivation membrane potential relationship of the Na system was shifted toward negative membrane potentials by the drug. It was also shown that in Ringer solution the reactivation time constant of the Na system (pi re) was faster at more negative membrane potentials than at more positive ones. The drug increased pi re; the increase was more marked when the membrane was depolarized. The block of Na conductance by the drug was partially removed by increasing the membrane potential to values more negative than -70 mV. The drug did not leave the channel or left it very slowly in the absence of clamp stimulation. The inhibition of the Na conductance by RP 30356 was also frequency-dependent. The data suggest that RP 30356 might be effective in the control of cardiac arrhythmias since it mainly decreased the excitability of depolarized fibres. PMID- 6265235 TI - Presence of a particular subpopulation of dopamine receptors within the septal nuclei: a behavioural study on cats. AB - The behavioural effects of intraseptal administration of dopaminergic drugs (apomorphine, haloperidol, (3,4-dihydroxy-phenylamino)-2-imidazoline (DPI), ergometrine and dopamine) and alpha-noradrenergic drugs (oxymetazoline, noradrenaline and phentolamine) were analysed in cats pretreated with morphine (5 mg/kg, i.p.). Changes in frequencies of stereotyped locomotor patterns were used for statistical evaluation of drug-induced effects. Taking advantage of the specificity of the drugs mentioned, a distinction could be made between effects mediated via excitation-mediating dopamine (DAe), inhibition-mediating dopamine (DAi) and alpha-noradrenaline (alpha-NA) receptors. Intraseptal injection of the DAi agonist DPI resulted in a decrease in the frequency of stereotyped locomotor patterns. This effect was dose-dependent and mimicked by that of intraseptally applied dopamine but not of any of the other drugs. Moreover, intraseptal injection of the DAi antagonist ergometrine inhibited the effect of DPI. The DAe agonist apomorphine as well as the DAe antagonist haloperidol remained ineffective when applied in low doses. The alpha-NA antagonist phentolamine and a rather high dose of haloperidol produced a slight but significant increase in the frequency of locomotor patterns; intraseptally applied oxymetazoline counteracted the phentolamine-induced effect. It is concluded that the septal nuclei of cats contain functionally active, alpha-NA receptors as well as functionally active, dopamine (DA) receptors having pharmacological properties identical to those of DA receptors present within the mesolimbic structures such as the nucleus accumbens: the so-called inhibition-mediating DAi receptors. PMID- 6265236 TI - Oximes: 'enzymatic' slow channel antagonists in canine cardiac purkinje fibers? AB - In mammalian cardiac muscle voltage-dependent activation of slow channels, e.g., the slow inward current channel, may be possible only when the channels are phosphorylated. We examined the electrophysiological actions of oximes, mile nucleophilic agents which show 'phosphatase-like' activity in isolated enzyme systems, to assess their actions on slow channels in cardiac Purkinje fibers. Diacetyl monoxime (DAM) and pyridine-2-aldoxime (NorPAM) produced a marked, reversible and concentration-dependent reduction in the action potential (AP) plateau duration and abolished spontaneous phase 4 depolarization, but produced only minimal effects on resting potential, dV/dt max, action potential amplitude, duration of phase 3, or membrane resistance. Slow response action potentials evoked in the presence of elevated potassium plus isoproterenol or in Na-free solution were abolished by DAM. The effects of DAM on the AP plateau were antagonized by epinephrine, but an increase in Ca was relatively ineffective. The results suggest that oximes may act as surrogate phosphatases to remove phosphate groups which regulate the availability of slow current channels for voltage dependent activation. PMID- 6265237 TI - Autoradiographic localization of CCK receptors in guinea pig brain. PMID- 6265239 TI - The depressant action of baclofen on the isolated spinal cord of the neonatal rat. AB - Neurotransmission in isolated hemisected spinal cord preparations from immature rats was depressed by micromolar levels of baclofen (threshold 0.5 microM). The depressant action of baclofen was not antagonised by bicuculline and baclofen, unlike GABA, did not depolarize primary afferent fibres. Neurotransmission in isolated vas deferens, anococcygeus muscle and superior cervical ganglion of the rat was unaffected by baclofen (0.1-1 mM). Depolarization of motoneurones, as recorded in ventral roots of tetrodotoxin-blocked spinal cord preparations, induced by excitant amino acids, substance P, noradrenaline or carbachol was unaffected by baclofen (250 microM or higher). The depressant action of baclofen on spinal cord preparations was similar to that produced by the excitant amino acid antagonist alpha,epsilon-diaminopimelic acid. A structure-activity study showed that the (--)-isomer of baclofen was over 20 times more potent than the (+)-isomer as a spinal depressant. Also the position and nature of the halogen substitutent in the ring is critical with baclofen giving optimal activity. It is concluded that the depressant action of baclofen from depression of the presynaptic release of excitant amino acid transmitter(s). PMID- 6265238 TI - Morphine suppresses the blood pressure responses to clonidine withdrawal in the spontaneously hypertensive rat. PMID- 6265240 TI - Inotropic effects and Na+,K+-ATPase inhibition of ouabain in isolated guinea-pig atria and diaphragm. AB - Effects of ouabain on force of contraction were compared in electrically driven isolated tissue preparations of guinea-pig left atria and diaphragm. A distinct and steady positive inotropic effect of ouabain was observed in atrial preparations, whereas in diaphragm preparations, ouabain produced only a slight and transient positive inotropic effect, followed by the negative inotropic phase. The transient positive inotropic effect of ouabain was observed even in the absence of extracellular calcium, but was markedly dependent on the extracellular sodium concentration. In vitro [3H]ouabain binding studies revealed that the affinity of Na+,K+-ATPase for ouabain was about eight times higher and tissue concentration of the enzyme was significantly lower in diaphragm than in cardiac tissue. The Ki value for ouabain inhibition of the cardiac Na+,K+-ATPase was also approximately ten times higher than for the diaphragm enzyme. Ouabain sensitive 86Rb uptake, an estimate of sodium pump activity, was inhibited by ouabain at a time when it produced its transient positive inotropic effect in diaphragm preparations. These results indicate that the lack of a distinct and steady positive inotropic effect of ouabain in diaphragm was due neither to the difference in the ouabain-Na+,K+-ATPase interaction between diaphragm and cardiac tissues nor the failure of sodium pump inhibition by ouabain in diaphragm. PMID- 6265241 TI - Prazosin selectively inhibits the responses to field stimulation in the rat vas deferens. AB - The effects of prazosin on contractile responses of the epididymal and prostatic halves of the rat vas deferens have been studied. In the epididymal half responses to acetylcholine were not altered by hexamethonium, 100 microM, but were inhibited by atropine, 10 nM. Prazosin, 100 nM, had no effect on maximal or submaximal responses to acetylcholine or methacholine. In the presence of cocaine, 10 microM, prazosin 10 and 100 nM, reduced the magnitude of the maximal twitch and sustained responses to field stimulation in the epididymal and prostatic halves of the vas deferens. Submaximal responses at all frequencies of stimulation and to exogenously applied noradrenaline were also inhibited by prazosin. Thus all responses to field stimulation of the epididymal and prostatic halves of the vas deferens are susceptible to selective alpha 1-adrenoceptor blockade with low concentrations of prazosin. PMID- 6265242 TI - Tetrahydroisoquinolines (TIQs) do not act on opiate receptors in the guinea-pig ileum. AB - The myenteric plexus-longitudinal muscle preparation of the guinea-pig ileum was stimulated with supra-maximal electrical field stimulation at 0.1 Hz. The contractile response was inhibited by salsolinol (1-300 microM) and tetrahydropapaveroline (THP) (3-30 micro M) but not by (cis)-3-carboxysalsolinol. S(-)-Salsolinol was more potent than R(+)-salsolinol. The inhibition by salsolinol and THP was unchanged by naloxone (up to 10 micro M). However, naloxone completely prevented the inhibition induced by normorphine, with a pA2 of 8.66. The results indicate that salsolinol and THP do not interact with opiate receptors in this preparation. PMID- 6265243 TI - Evidence that ethanol and pentobarbital enhance [3H]diazepam binding at the benzodiazepine-GABA receptor-ionophore complex indirectly. PMID- 6265244 TI - DSP4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine)--a useful denervation tool for central and peripheral noradrenaline neurons. AB - The effect of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) on monoamine neurons was studied in mice and rats. In mice DSP4 produced acutely a marked reduction of endogenous noradrenaline (NA), [3H]NA uptake and nerve density of the adrenergic nerves in the iris and atrium. Pronounced accumulations of NA were observed in non-terminal axons, which is a degenerative sign, while no changes were found in the NA cell bodies. A marked recovery of all parameters analysed was found as soon as 1 week after DSP4. In the mouse CNS, however, there was a marked and long-lasting NA reduction, especially in the cerebral and cerebellar cortex and spinal cord, leaving dopamine (DA) and serotonin (5-HT) neurons apparently unaffected. Administration of DSP4 to adult rats produced regional changes in the NA levels of the CNS were similar to those observed in the mouse. There were no indications of DSP4 affecting dopamine and adrenaline neurons in rat CNS, although a minor 5-HT depleting effect was noted. DSP4 treatment resulted in an increase in beta-adrenoceptor binding in vitro to homogenates from the cerebral cortex, using [3H]dihydroalprenolol as radioligand. Treatment of newborn rats with DSP4 caused permanent NA disappearance in the cerebral cortex and spinal cord, whereas marked NA increases were found in the pons-medulla and cerebellum. Administration of DSP4 to pregnant rats (gestation day 15) led to a marked and permanent NA depletion in the cerebral cortex and spinal cord in the offspring. The results support the view that DSP4 can produce an acute and relatively selective degeneration of NA nerve terminals in the rat and mouse. The results furthermore indicate that DSP4 (systemically administered) causes a preferential degeneration of NA nerve terminal projections originating from the locus coeruleus in the CNS. Since DSP4 can pass both the blood-brain and blood placenta barrier and appears to have potent neurotoxic actions on NA neurons, DSP4 may serve as a useful denervation tool for the analysis of NA transmitter functions, particularly in the CNS of both adult and developing animals. PMID- 6265245 TI - Calcium dependence of prejunctional inhibitory effects of adenosine and acetylcholine on adrenergic neurotransmission in canine saphenous veins. AB - In canine blood vessels acetylcholine and adenosine inhibit the exocytotic release of norepinephrine during nerve stimulation. The present experiments were designed to determine the Ca2+ dependence of these prejunctional effects. Segments of canine saphenous veins were mounted for isometric tension recording in organ chambers filled with Krebs-Ringer or Tyrode solution. Altering the Ca2+ concentration of the solution did not affect the inhibitory response to acetylcholine during nerve stimulation; the prejunctional potency of adenosine was inversely related to the Ca2+ concentration of the bath content. the ionophore A23187 caused contractions which were inhibited by phentolamine, verapamil, and adenosine but were augmented by acetylcholine. Helical strips of dog saphenous veins were incubated in [3H]norepinephrine and mounted for superfusion and determination of [3H]norepinephrine in the superfusate. A23187 increased the overflow of [3H]norepinephrine. Acetylcholine augmented this efflux; by contrast adenosine decreased the release induced by the ionophore. The results demonstrate that the prejunctional effect of acetylcholine was not due to direct interference with the availability of Ca2+ for the electro-secretory process in adrenergic nerve terminals and suggest that adenosine interferes either with the coupling role of the activator ion or its extrusion from the neuroplasm. PMID- 6265246 TI - Trapidil stimulation of slow Ca2+ current in cardiac muscle. AB - The effect of trapidil, a coronary vasodilator and positive inotropic agent (associated with elevated tissue cyclic AMP levels due to phosphodiesterase inhibition), was examined on the electrophysiological properties of cardiac muscle. Specifically, the trapidil was tested for its ability to induce slow action potentials (APs), and to affect the maximum upstroke velocity (+Vmax) of the slow APs in the ventricular myocardial cells of isolated perfused chick hearts. The effect of trapidil on the contractions accompanying the slow APs and on the tissue cyclic AMP levels was also examined. To study the slow channels exclusively, the fast Na+ channels were voltage-inactivated by elevated (25 mM) K+. In this condition of functional removal of the fast channels, the hearts could not be excited even by intense electrical stimulation. It was found that trapidil (10(-4)--10(-3) M) induced slow APs accompanied by contractions. Elevation of the trapidil concentration produced dose-dependent increases in +Vmax, dT/dt (first derivative of developed tension) and cyclic AMP. These effects of trapidil were not affected by propranolol, suggesting that they were not mediated by beta-adrenergic receptors. These results support the hypothesis that intracellular cyclic AMP levels regulate the number of available slow channels, thereby controlling contractile force in the heart muscle via the Ca2+ influx mediated by slow channels. PMID- 6265247 TI - beta-Adrenoceptor activation induces prostaglandin E2 generation in guinea-pig trachea. AB - Isoproterenol and salbutamol caused relaxation of guinea-pig trachea, and generation of PGE2. The phenomenon appears to be specific for beta-adrenergic agonists since the relaxant activity induced by atropine, theophylline and papaverine was not associated with generation of prostaglandin-like material from tracheal smooth muscles. Indomethacin reduced only slightly the relaxation of the tracheal tissue induced by isoproterenol and salbutamol. The possibility is discussed that the increased arachidonic acid metabolism during trachea beta adrenergic relaxation represents a metabolic event involving phospholipid methylation and membrane fluidity. PMID- 6265248 TI - Plasma-converting enzyme activity does not reflect effectiveness of oral treatment with captopril. AB - Intravenous Captopril (20 microgram) in rats produced similar inhibition of the pressor responses to intravenous ANG I (70%) and of plasma-converting enzyme activity (CEA) measured fluorometrically (72%). One week oral treatment with Captopril (50 mg/kg per day) inhibited ANG I pressor responses more (84%) than plasma CEA (23%). Four-month oral treatment of normotensive and spontaneously hypertensive rats with Captopril (50 mg/kg per day) led to a 68% and 71% inhibition of the ANG I pressor responses, but to a 123% and 94% increase of plasma CEA, respectively. Thus, plasma CEA measurements can be dissociated from the in vivo inhibition of converting enzyme (CE). Chronic oral Captopril treatment induces CE biosynthesis. PMID- 6265250 TI - Effect of transformation of chicken cells by Rous sarcoma virus on in vitro phosphorylation of nuclear non-histone proteins. PMID- 6265249 TI - Down-regulation of beta-adrenergic activity in astroglia by chronic treatment with an antidepressant drug. PMID- 6265251 TI - Phosphorylation of cleavage stage histone H1 in mitotic and prematurely condensed chromosomes. PMID- 6265252 TI - The effects of topically applied epinephrine and timolol on intraocular pressure and aqueous humor cyclic-AMP in the rabbit. PMID- 6265253 TI - Dependence on Na+ of kinetics of the lenticular Na+, K+-activated ATPase. PMID- 6265254 TI - Calcium controls both sodium and potassium permeability of lens membranes. PMID- 6265255 TI - Mediators of feedback message: estrogens and/or catechol-estrogens? PMID- 6265256 TI - Anatomical relationships between estrogen target sites and peptidergic-aminergic neurons: multiple activation of heterogeneous systems (MAHS). PMID- 6265257 TI - Neuronal discrimination of natural and synthetic vowels in field L of trained mynah birds. AB - The discrimination of single neurons for vowels and vowel components was analyzed in the telencephalic field L which is a layered and tonotopically organized primary auditory projection area in the bird's neostriatum. Among 250 units, 132 (53%) were responsive to at least one out of nine vowels from one German speaker. The distribution of responsiveness to n (one to nine) vowels showed that a maximum of 33 out of the 132 neurons preferred n = one vowel. The mechanisms of vowel selectivity were analyzed with five synthetic vowels composed of two formants F1 and F2 which could be presented separately. Most of the selective units also responded to F1 or F2 of the preferred vowel alone. The suppression of the vowels could be explained by formants which fell into inhibitory ranges of that unit, independently demonstrated by the pure tone response. Other units had several excitatory bands which coincided with the formants of the preferred vowel. In some cases a certain amplitude ratio of F1 versus F2 gave the strongest response. Several qualitative models of excitatory-inhibitory interaction of inputs to field L neurons are presented which explain the described selectivities. It is interesting that the distribution of vowel-selective units relates to the most superficial and most basal layer of field L where units selective for species-specific calls have previously been located in a gallinaceous bird. PMID- 6265258 TI - Differential responsiveness of cells in the visual zones of the cat's LP-pulvinar complex to visual stimuli. AB - Multiple visual field representations are contained within the feline LP-pulvinar complex; regions differentiated by their afferent and efferent connectivity patterns as the striate-, tecto- and retino-recipient zones. Cell responses from these visuotopic zones were investigated in immobilized cats under N2O/O2 supplemented with pentobarbitone or Althesin, using spot, bar and textured stimuli. Response fields recorded within the LP-pulvinar complex were classified as diffuse, concentric, movement-, direction- or orientation-sensitive. Concentric receptive fields were further classified as sustained (X), transient (Y) or tonic/phasic W-cells. Direction- and movement-sensitive cells predominated in the striate- and tecto-recipient zones, respectively. Motion of noise fields, or noise bars against an identical stationary noise background elicited vigorous responses from cells in the striate zone, many showing a preference for noise stimuli. In contrast, cells from the tectal zone and other divisions of the LP pulvinar complex were insensitive to noise. The retino-recipient zone at the lateral margin of the pulvinar nucleus was characterized by cells with concentric receptive fields, the majority exhibiting properties similar to W-cells in the LGNd. The evidence supports the notion of functional subdivision within the LP pulvinar complex corresponding to the visuotopically organized regions defined by their connectivity patterns. Consideration of the retino-recipient zone as an extension of the LGNd-MIN complex is discussed. PMID- 6265259 TI - Patterns of parallel signal transmission between multiple alpha efferents and multiple Ia afferents in the cat semitendinosus muscle. AB - 1. Certain features of signal transmission from multiple alpha-axons to multiple Ia fibres via extrafusal muscle tissue were studied by stimulating three ventral root filaments separately and simultaneously and by recording spike trains from three dorsal root filaments. 2. Post-stimulus time histograms (PSTH) revealed widely graded influences of single motor unit contractions on different muscle spindles, thus confirming results of Binder et al. (1976, 1980a). 3. In most instances, the signal transmission from a single motor unit to a single Ia fibre was disturbed to varying degrees by concomitant activity from other motor units. 4. This deterioration of signal transmission can probably be compensated for, at least in part, by correlations between discharge patterns of two or more Ia fibres induced by the "common input" of motor unit activity. 5. These correlations showed a topographical pattern such that a peak in the cross correlogram (CCH) occurred at zero time for pairs of spindles located virtually in parallel to each other, and was shifted away from zero time as a function of the serial distance between spindles in the longitudinal muscle fibre direction. 6. Fusimotor innervation had complex effects on correlations between Ia fibre discharge patterns. It might de-correlate the latter as well as favour new correlations. 7. The possible role of topographical correlation patterns in the afferent reflex limb for tremor suppression is discussed. PMID- 6265261 TI - Reflexes evoked in leg muscles from arm afferents: a propriospinal pathway in man? AB - Long-loop reflexes from arm afferents onto motoneurones of leg muscles were investigated in 57 healthy subjects by means of H reflex testing and tonic EMG testing. In various tonically activated leg muscles, brachial nerve stimulation exerted stereotyped reflex responses which regularly consisted of an initial depression phase (mean onset latency: 60 ms) and a subsequent facilitatory phase (mean onset latency: 80 ms). H reflex studies, in contrast, only revealed the later facilitation. Except for this difference, both methods led to similar results: fibres responsible for the response were identified as low-threshold skin afferents with a conduction velocity of about 40 m/s. Noxious stimulation reinforced the effects of innocuous stimulation. The receptive field for the reflex response was not restricted to the ipsi- and contralateral arm regions but included the face and the rostral part of the trunk above the buttock. Percutaneous stimulation of dorsal roots C4 and T9, respectively, resulted in a shortening of the onset latencies of both depression and facilitation, with T9 stimulation. It is therefore suggested that the reflexes described are mediated via a directly descending, long spinal pathway. PMID- 6265260 TI - Relationship between input and output of cells in motor and somatosensory cortices of the chronic awake rat. A study using glass micropipettes. AB - Experiments using the same glass microelectrode (6--8 M omega) for recording and stimulating were performed on 12 rats in which 379 cortical cells were studied in 65 penetrations through the motor and somatosensory cortical zones. To avoid anaesthetic effects the rats were chronically implanted with a head system derived from the one developed by Noda et al. (1971). These animals well accepted head fixation and the peripheral receptive fields could thus be easily investigated. In a preliminary experiment the number of pyramidal cells activated by a given stimulus intensity was evaluated. The lowest threshold intensities were always observed in the Vth pyramidal layer, as well as correspondence between cell input and output. The same type of organization, with identical thresholds, existed in the so-called "Motor" and "Somatosensory" cortical zones. Movements could be obtained when stimulating near non-PT cells (600--700 micron below the cortical surface). However, thresholds were higher at this level and it is thought that the movements were due to a spread of the stimulating current to the pyramidal tract cell layer. PMID- 6265262 TI - Neural delay in the ascending auditory pathway. AB - Evoked responses from the cochlea and cochlear nucleus in the rat were studied using two types of stimuli: (1) bursts of tones or noise, and (2) continuous tones or noise that were amplitude modulated with pseudorandom noise. While the responses to the first type of stimuli were averaged only in the conventional way, the responses to the continuous and amplitude modulated sounds were averaged over one period of the pseudorandom noise. This average was then cross correlated with one period of the noise. The morphology of these cross correlation functions was in many ways similar to the response to transient sounds. Recordings from the round window of the cochlea and the cochlear nucleus showed that the latencies of these peaks in the responses to tone bursts and those of the cross correlation functions obtained from the continuous tones modulated with pseudorandom noise were similar. However, the latencies of the peaks in the cross correlation functions were slightly shorter and showed less dependency on the stimulus intensity than did the peaks in the responses to tone bursts. When the responses to noise bursts and the responses to noise that was amplitude modulated were compared, it was found that the latencies of the peaks in the cross correlation functions were nearly independent of the stimulus intensity. However, the peaks in the averaged responses to noise bursts showed a decrease in latency with increasing sound intensity. PMID- 6265264 TI - Inhibitory actions of amino acids in the preoptic-anterior hypothalamus of the rat. AB - Extracellular recordings were made from preoptic-anterior hypothalamic neurones with combined recording and iontophoresis electrodes. Short iontophoretic applications of beta-alanine, GABA, glycine and taurine inhibited the discharge of the majority of neurones tested. Bicuculline metho-chloride reversibly and selectively antagonised GABA responses. Strychnine reversibly antagonised beta alanine, glycine and taurine but not GABA responses. These results suggest the existence of two populations of inhibitory amino acid receptors in the preoptic anterior hypothalamus. The function of inhibitory amino acids in the rostral hypothalamus was briefly discussed. PMID- 6265263 TI - Classification of receptive field properties in cat visual cortex. AB - The properties of the receptive fields of visual cortex neurons of cats were studied manually and by a computer controlled system using single lines, double lines and multiple lines (gratings). The multiple selectivities of each of the receptive fields studied make it necessary to abandon the concept that each cell functions as a feature detector. Instead, an attempt was made to classify the receptive field properties with the aim to delineate the transfer functions (of the total networks) served for each property. When tested with one-line stimulus, cells with simple receptive field properties differed from cells with complex receptive field properties as to their velocity selectivity (simple: 1 degree to 3 degrees/s; complex: 4 degrees to 10 degrees/s), spontaneous activity (lower for cells with simple properties) optimal firing rate (lower for cells with simple properties) and receptive field size (smaller for cells with simple properties) but not for orientation and direction selectivity. When tested with a 2-lines moving stimulus, the responses of cells with simple properties were facilitated by the progressive separation of the lines whereas the responses of cells with complex receptive field properties were inhibited. When multiple line, i.e., gratings, were used, an equivalence between simple and X properties and complex and Y properties was shown, while the sustained/transient classification proved to be independent of the simple/complex (X/Y) classification. Thus, receptive field properties can be classified into three categories: one reflects the input to the receptive fields; a second deals with the interactive properties of the fields; while a third appears more related to the overall properties of the network. PMID- 6265266 TI - Inhibition, disinhibition, and summation among orientation detectors in human vision. AB - A vertical test line viewed together with an oblique inducing line appears to be tilted in the opposite direction (orientation contrast); a similar effect results from adapting to an oblique line before presenting the test line (tilt after effect). The error in perceived orientation caused by a clockwise tilted inducing line may be partially cancelled by a second clockwise tilted inducing line; likewise, adapting to a configuration of two clockwise orientations gives weaker tilt after-effects than adapting to the more effective of the two orientations alone. The angular functions of these "disinhibitory" effects mirror the angular functions of the principal effects. However, combining tilt after-effect and simultaneous contrast in a disinhibition design by having the subject first adapt to a clockwise orientation and then presenting the test line together with a clockwise inducing line results in partial summation rather than disinhibition. The results are consistent with Carpenter's and Blakemore's (1973) hypothesis that orientation contrast and the tilt after-effect are manifestations of cortical inhibition in a network of inhibitory, recurrent lateral connections between cortical orientation detectors. After-effects must be due to prolonged inhibition, probably caused by a sensitivity change in previously inhibited detectors. PMID- 6265267 TI - Further electrophysiological studies of neuromuscular transmission in an animal model of myasthenia gravis. PMID- 6265268 TI - Electron microscopy of polyps of the colon. II. Inclusion bodies of Leuchtenberger. AB - The electron-microscopic characteristics of the LEUCHTENBERGER'S inclusion bodies were studied in adenomatous, papillary and adeno-papillary polyps of the colon. According to them, formation of intracellular inclusions is due to focal cytoplasmic degradation, and that of intercellular inclusions to the herniation of the cytoplasmic part of epithelial cells. The formation of inclusions is believed to be connected with the low stage of development of the plasma membrane of rapidly proliferating undifferentiated colonic epithelial cells. During malignant transformation of polyps, the frequently occurring inclusions are considered an important morphological sign. PMID- 6265265 TI - Neocortical cholinergic innervation: a description of extrinsic and intrinsic components in the rat. AB - Electrothermic lesion of the peri-pallidal region of the rat caused a marked reduction in the activity of choline acetyltransferase in the ipsilateral fronto parietal cortex without affecting the activity of glutamate decarboxylase. Only lesions that involved the ventral globus pallidus significantly reduced cortical choline acetyltransferase activity; and lesions limited to the thalamus, internal capsule, pyriform cortex or zone incerta were ineffective. Excito-toxin lesions of the ventral globus pallidus caused 45-5% reductions in all presynaptic markers for cholinergic neurons but did not significantly decrease presynaptic markers for noradrenergic, serotonergic or histaminergic neurons in the cortex. The maximal reductions in cortical choline acetyltransferase activity achieved with the pallidal lesion was 70%; and enzyme activity reached its nadir by four days after placement of the lesion. The pallidal lesion, which ablated the large isodendritic acetylcholinesterase positive neuronal perikarya, resulted in a profound loss in histochemically stained acetylcholinesterase-reactive fibers in the fronto-parietal cortex but not in the cingulate, pyriform and occipital cortex or hippocampal formation; analysis of the subregions in choline acetyltransferase activity. The kainate lesion of the parietal cortex to ablate intrinsic neurons did not reduce the activity of tyrosine hydroxylase, a marker for noradrenergic terminals, but depressed glutamate decarboxylase by 68%; in contrast choline acetyltransferase activity fell only 29%. The results indicate that approximately 70% of the cholinergic innervation in the fronto-parietal cortex is derived from acetylcholinesterase positive neurons in the peripallidal nucleus basalis, whereas the remainder appears to be localized in cortical intrinsic neurons. PMID- 6265270 TI - Development of nucleoside phosphotransferase activity in the cerebral hemispheres of embryonal and adult chick. AB - In the cerebral hemispheres of the chick embryo, the level of nucleoside phosphotransferase activity is much higher than that of thymidine kinase and it increases progressively during development up to the adult stage. Therefore nucleoside phosphotransferase is not coupled with DNA synthesis. PMID- 6265269 TI - Histochemical studies of oxidoreductases in rat kidney regenerating after mercuric chloride injury. AB - The activities of succinic dehydrogenase, glucose-6-phosphate dehydrogenase, lactate dehydrogenase and cytochrome oxidase, representatives of the tricarboxylic acid cycle, pentose phosphate pathway, glycolysis and terminal oxidation, respectively, were investigated after necrosis induced with mercuric chloride. 24 hours after the administration of mercuric chloride, the activities of all four enzymes were decreased in the necrotic proximal tubular segments. By the third day of regeneration the activities had decreased or disappeared in all three portions of the necrotic proximal tubules as compared to the 24-hour situation, but they remained constant in the distal tubules; the activity of G6PDH was rather increased. Between the 5th and 12th days the activities gradually increased in the regenerating proximal tubules, while the G6PDH activity of the distal tubules remained elevated, and by the 3rd to 4th week the activities were the same as those in the control animals. Our histochemical results complement the earlier biochemical results of analyses of tissue homogenates localizing the changes of enzyme activity. The histochemical studies suggest that the non-necrotic parts of the nephron contribute to the supplies of energy and substances to the regenerating cell. PMID- 6265271 TI - Correction of the anomalous electrophoretic behavior of ribonuclease A. AB - Ribonuclease A behaves anomalously on polyacrylamide gel electrophoresis at acid pH. The distance traveled by the protein is a function of the amount of enzyme added at the lower range of detectable activity (10 pg to 100 ng). Addition of myoglobin (1 mg/ml) abolishes the anomaly. The observations are consistent with the known affinity of RNase for anions. Caution is warranted in the interpretation of apparent electrophoretic variants of RNase observed at low concentrations of enzyme. PMID- 6265272 TI - The effect of dietary fibre on 85Sr and 47Ca absorption in infants rats. PMID- 6265273 TI - Ultrastructural localization of glucose 6-phosphatase activity in the cells of the epididymis of the mouse. PMID- 6265275 TI - A simple filtration device to study the interaction of RNA-polymerase with DNA. PMID- 6265274 TI - Adenylate cyclase of a human medullary thyroid carcinoma. PMID- 6265276 TI - Conversion of active protein phosphatase to the ATP-Mg-dependent enzyme form by inhibitor-2. PMID- 6265277 TI - EGF inhibits glucagon stimulation of amino acid transport in primary cultures of adult rat hepatocytes. PMID- 6265278 TI - The loss of muscarinic acetylcholine receptors in synaptic membranes under phosphorylating conditions is dependent on calmodulin. PMID- 6265279 TI - Purification of a gamma-aminobutyric acid receptor-like constituent of bovine brain. PMID- 6265280 TI - The interaction of Graves' IgG with the thyrotrophin receptor. PMID- 6265282 TI - Involvement of DNA gyrase in the replication and transcription of mycobacteriophage I3 DNA. PMID- 6265281 TI - Anthraquinone dyes: a new class of potent inhibitors of mitochondria adenine nucleotide translocation and oxidative phosphorylation. PMID- 6265283 TI - Separation of two nonidentical cAMP binding sites in the cAMP-dependent protein kinase type I. PMID- 6265284 TI - Role of dietary fiber in diverticular disease and colon cancer. AB - This paper reviews recent research on the characterization, properties, and definition of dietary fiber as well as its possible role in colonic carcinogenesis and diverticulosis. Despite progress in analytic methods and characterization, an accepted definition and terminology for fiber are lacking as is an accurate, rapid method for measurement of total dietary fiber or fiber in foods. Mechanisms of effects of fiber in the gut and the significant of interactions between fiber, nutrients gut flora and associated metabolites, and enteric secretions are unclear. Epidemiologic and experimental data indicate an increased risk of diverticular disease and colonic cancer with low-fiber intakes; however, genetic, environmental, cultural, dietary, and other variables were often uncontrolled in the epidemiologic studies. Thus, conclusive evidence for a causal relationship between low intake of fiber and diverticulosis or colonic cancer is not available, and the question whether first protects against human colonic cancer and/or diverticulosis is not completely resolved. Clinical trials in which symptomatic diverticular disease was treated with supplementary dietary fiber have generally had favorable results. Numerous specific questions require additional study before a role for dietary fiber in the prevention of human colonic diverticulosis and cancer of the colon can be established. Suggestions for possible future investigation are provided. PMID- 6265285 TI - Symposium summary. Neuronal activity and energy metabolism. PMID- 6265286 TI - Central respiratory rhythmicity. Introductory remarks. PMID- 6265287 TI - Problems of epithelial potassium transport: special consideration of the nephron. PMID- 6265288 TI - Potassium transport by successive segments of the mammalian nephron. AB - Potassium excreted by the kidney is derived largely from potassium secretion by the distal tubule and collecting duct. It is this secreted fraction that responds to systemic changes and is mainly responsible for regulation of potassium balance. A smaller fraction of the excreted quantity comes from potassium that is filtered and escapes reabsorption. Variations in the rate of reabsorption may alter potassium secretion under some circumstances. In the proximal tubule, reabsorption of potassium appears to involve interaction with a membrane mechanism. The contribution of descending limb potassium secretion to final potassium secretion is a present uncertain because of the inaccessibility of inner cortical distal tubules and collecting ducts in intact animals. Changes in plasma K, plasma aldosterone, and plasma acidity all appear to affect distal potassium secretion by influencing the uptake of potassium from blood to cell and thus raising the intracellular potassium. Changes in extracellular fluid volume, which increase urine flow and sodium excretion, appear to increase distal potassium secretion as a consequence of increases in the flow rate of luminal fluid. Flow-dependent changes in luminal potassium concentration may be involved but they do not appear to act by simply increasing the passive electrochemical driving force (assessed across the entire epithelium). Our understanding of the cellular mechanisms controlling renal potassium secretion is becoming clearer as it becomes possible to identify and to separate for a study a potentially confusing array of interacting variables. PMID- 6265289 TI - Potassium secretion by the cortical collecting tubule. AB - The isolated perfused rabbit cortical collecting tubule has been shown to actively transport K from bath to lumen. The first step in this process is active uptake of K across the basolateral membrane via and Na:K exchange pump as evidenced by: 1) basolateral localization and Na:K exchange properties of the ouabain-sensitive Na,K-ATPase, 2) ouabain sensitivity of the Na and K fluxes, 3) interdependence of the Na and K fluxes, and 4) ouabain-sensitivity of 42K uptake into the cell across the basolateral membrane. At the luminal border, a significant K permeability of the apical cell membrane has been identified using electrophysiological techniques. This K permeability is insensitive to the diuretic amiloride, and, thus, differs from the pathway for Na entry, which is highly amiloride sensitive. A significant K permeability of the paracellular pathway is not apparent. It is concluded that K secretion by the rabbit cortical collecting tubule occurs via a two-step process: active uptake of K across the basolateral membrane via the Na:K exchange pump, followed by passive efflux of K across the apical membrane via an amiloride-insensitive K conductive pathway. PMID- 6265290 TI - Potassium transport by rabbit descending colon, in vitro. AB - Studies of the bidirectional fluxes of K across segments of rabbit descending colon indicate that: a) when the tissue is short-circuited, the net flux does not differ significantly from zero under control conditions and in the presence of aldosterone; and b) the bidirectional fluxes of K conform to the Ussing flux ratio equation over a wide range of transepithelial electrochemical potential differences. These and other findings strongly suggest that the movements of K across the epithelium are restricted to paracellular routes and are entirely passive. Studies dealing with the mechanism of homocellular K transport indicate that: a) K is actively transported into the cells across the basolateral membranes against an electrochemical potential difference of approximately 30 mV; and b) the active uptake of K may be mediated by a rheogenic Na-K exchange pump that is also responsible for transcellular Na transport. These results are entirely consistent with the model proposed by Koefoed-Johnson and Ussing for isolated frog skin. PMID- 6265291 TI - Active transport of potassium by insect midgut. AB - Midguts isolated from fifth-instar larvae of the insert Hyalophora cecropia actively transport potassium in the hemolymph to lumen direction. No specific co- or counter-ion is required and other alkali ions are actively transported in the same direction as potassium. No specific inhibitor of K+ active transport has been found although most metabolic inhibitors reduce the net K+ flux, potential difference, and short-circuit current to zero. The site of the epithelial active transport of potassium has been identified by microelectrode measurements of intracellular resistance as the goblet cell, one of the two major cell types in the single-layered midgut. Under certain external conditions, the neighboring columnar cells are added to the goblet cell transport route through intercellular electrical coupling that occurs after application of external depolarizing current. Tracer influx kinetics were used to establish that the fraction of exchangeable K involved in the transport route under open-circuit conditions is small, corresponding to a goblet cell pathway. Under depolarizing current conditions, virtually all of the exchangeable midgut K is involved in the transport route, corresponding to a goblet and columnar cell pathway. These results and others are used to construct a model for rheogenic active transport of potassium in insect midgut. PMID- 6265292 TI - delta 9-tetrahydrocannabinol inhibits fructose utilization and motility in human, rhesus monkey, and rabbit sperm in vitro. PMID- 6265293 TI - [Changes in lymph flow during reflexes from lymph vessels]. PMID- 6265294 TI - [Role of "secondary transmitters" in the exocrine function of the pancreas]. AB - In animals, exogenous secretin produces dose--related increases in pancreatic tissue levels of cyclic AMP which are closely correlated with both bicarbonate and cyclic AMP outputs in pancreatic juice. These effects can be augmented by additional administration of phosphodiesterase inhibitors such as methylxanthines. Vasoactive intestinal peptide (VIP) produces similar though less pronounced effects than secretin. Following secretion or VIP the changes in pancreatic tissue cyclic AMP concentrations precede the physiological response, i.e. enhance water and electrolyte secretion. In man, bicarbonate and cyclic AMP concentrations of pure pancreatic juice obtained by endoscopic cannulation of Vater's papilla are significantly correlated in response to both secretin and VIP. VIP however, has a lower efficacy and potency relative to secretin. There is no significant correlation between pancreatic juice cyclic GMP and bicarbonate concentrations or outputs. These observations suggest that cyclic AMP plays an important role in mediating the stimulatory effects of secretin and VIP on hydrokinetic pancreatic exocrine function. However, it still remains to be elucidated in which specific way cyclic AMP initiates the secretory process. In principle, the action of cyclic nucleotides on cell function is thought to occur from their ability to activate cyclic nucleotide--dependent protein kinases which in turn are capable of activating enzymes of protein synthesis by phosphorylation (19). With respect to pancreatic secretion, studies of this kind are currently under way. PMID- 6265295 TI - [Analysis of opposite changes in pO2 on the surface of leech Retzius neurons when synaptically activated]. PMID- 6265296 TI - [Angiodysplasia in children]. PMID- 6265297 TI - T cell defect in patients with epidermodysplasia verruciformis due to human papillomavirus type 3 and 5. AB - Most of the patients with epidermodysplasia verruciformis (EV) were anergic to sensitization to dinitrochlorobenzene (DNCB) and were shown to have a decreased number of T lymphocytes and reduced lymphocyte PHA responsiveness. Preserved cell mediated immunity (CMI) was found only in the abortive cases of EV infected with human papillomavirus type 3 (HPV-3). CMI was impaired to the same extent in patients with EV induced by HPV-3 and HPV-5, and in EV cases with combined infection with both viruses. In contrast to this, malignant transformation, i.e. of Bowen's carcinoma type, was observed only in the 7 patients infected with HPV 5. This could indicate that malignancy in EV is related rather to the oncogenic potential of HPV-5 type than to the extent of T cell defect that was similar in both EV varieties due to HPV-3 and HPV-5. PMID- 6265298 TI - Long term effects of dietary fibre in bread on weight, blood glucose, glucosuria and faecal fat excretion in alloxan diabetic rats. AB - A comparative study of the long term effects of high and low fibre diets on weight, blood glucose levels, urine glucose excretion and faecal fat excretion was carried out on alloxan diabetic rats and controls rats. The experimental diet consisted of bread and milk. The high fibre bread was made from bran enriched whole rye meal and the low fibre bread from refined rye meal. All rats received the diets for six weeks. Diabetic rats on high or low fibre diets had essentially the same intake of other nutrients. The weight loss was less in the diabetic animals on the high fibre bread than on the low fibre bread. The control animals on the high fibre diet had slightly lower body weights and lower blood glucose levels than those on the low fibre diet. In diabetic rats the blood glucose levels were lower on the high fibre diet than on the low fibre diet. The urinary glucose excretion in diabetic rats decreased immediately after the start of the high fibre diet, while it increased in the rats on the low fibre diet. Faecal fat content in relation to fat intake was greater in the animals on high fibre diet than in those on low fibre diet. PMID- 6265299 TI - Decreased urinary glucose excretion and plasma cholesterol level in non-insulin dependent diabetic patients with guar. AB - The effect of guar gum in lowering urinary glucose excretion and plasma cholesterol was studied in ten sulphonylurea-treated non-insulin dependent diabetic patients during a four week treatment period. The 24-hour urinary glucose excretion fell gradually and increased again to pretreatment value after withdrawal of guar. The glucose output dropped by 33 and 51% in the 3rd and 4th week of the guar treatment period (p less than 0.01) compared to the mean of the pre-plus postguar level. The plasma cholesterol concentration also fell significantly during treatment with guar (p less than 0.01). PMID- 6265300 TI - The preejection period of the fetal cardiac cycle. II. Maternal common internal iliac artery occlusions. AB - The preejection period (PEP) of the fetal cardiac cycle was studied in the chronically instrumented fetal lamb. An inflatable cuff occluder was positioned around the maternal common internal iliac artery, the pregnant ewe's main uterine blood-supplying vessel. Occlusion of the maternal common internal iliac artery produced a fall in pO2 and pH and a rise in pCO2. Fetal arterial blood pressure increased and PEP shortened, especially in the longer lasting occlusions. Fetal heart rate exhibited a bradycardia also during this type of occlusion. The fetal lamb's cardiovascular adjustments to biochemical changes caused by occlusion of the maternal uterine blood supply appear to be determined during the initial phase of occlusion by a chemoreceptor reflex-induced peripheral vasoconstriction mediated by the adrenergic nervous system. The condition is comparable to the one observed during the second part of the umbilical cord occlusions. The interaction between a supersensitive fetal myocardium and the adrenal release of catecholamines may play a dominant role during the second part of occlusion in the longer lasting experiments. Increase in peripheral resistance in the course of redistribution of blood flow during hypoxemia induces a prolongation of the PEP in the early phase of occlusion; overriding of this effect by an increase in myocardial contractility due to rising levels of adrenal catecholamines abbreviates the PEP in the later part of the longer lasting occlusions. PMID- 6265301 TI - Experimental study of hormone receptor development in a unicellular model system. AB - It was shown earlier that diiodotyrosine (T2) stimulates the growth of Tetrahymena. In the present study clonal populations of Tetrahymena, derived from subcultures propagated in the presence of T2, showed a highly significant increase of intra-clone variance over the control, while inter-clone variation was significant, but not decisive. This suggests that genetic factors play a smaller role in the development of the cell membrane receptor pattern tha the genetic variability of the membrane itself, which seems to account for the stabilization of the adequate receptors on first exposure to a hormone. PMID- 6265304 TI - Development of rat neuromuscular junctions in organ culture. PMID- 6265302 TI - Porcine granulosa and cumulus cell properties. LH/hCG receptors, ability to secrete progesterone and ability to respond to LH. AB - In order to compare the properties of isolated cumulus and granulosa cells, granulosa cells and cumulus cells surrounding oocytes were harvested from small (1-2 mm), medium (3-5 mm) and large (6-12 mm) porcine antral follicles and the number of LH/hCG receptors was measured by the binding of [125I]hCG. The ability of the cells to secrete progesterone in culture was examined in the presence and absence of hCG and LH. In 3 separate experiments of 1-h incubations at 37 degrees C using cells harvested from medium-sized follicles, granulosa cells bound 10--15 fold more iodinated hCG than an equivalent number of cumulus cells. During a 2 day culture period, cumulus cells secreted less progesterone than granulosa cells from medium- and large-sized antral follicles (p less than 0.01). The potential of both cumulus and granulosa cells to secrete progesterone in culture increased as the follicle progressed from small to large size. Also, the ability of the oocyte to mature in culture increased with antral follicle size. Concurrently the ability of cumulus-oocyte complexes to form monolayers in culture decreased as the follicle matured. Cumulus and granulosa cells harvested from small- and medium-sized follicles responded similarly to LH and hCG with a stimulation in progesterone secretion after 2-6 days in culture. PMID- 6265303 TI - Dynamic changes of the egg cortex. PMID- 6265306 TI - Infantile spasms: CSF proteins before and during treatment with ACTH. PMID- 6265305 TI - Cell differentiation in the absence of intracellular cyclic AMP pulses in Dictyostelium discoideum. PMID- 6265307 TI - [Evaluation of the survival of patients with bronchogenic carcinoma]. PMID- 6265308 TI - [Lack of effect of phenobarbital on bile flow and Na+,K+-ATPase activity of liver plasma membranes in the hamster (author's transl)]. PMID- 6265309 TI - Intestinal cryptosporidiosis complicated by disseminated cytomegalovirus infection. AB - A 48-yr-old man with profuse diarrhea for about 9 mo was found to have intestinal cryptosporidiosis. Treatment with antibacterial, antimalarial, and other antiprotozoal agents failed to control the disease. The organisms were identified by light and electron microscopy in a biopsy specimen from the duodenum. Disseminated infection with cytomegalovirus developed during treatment, and the patient died. Five other instances of intestinal cryptosporidiosis have been reported. Immunologic incompetence, related to either disease or therapy, or both, was present in 4 cases but, although suspected, could not be proved in the patient described in this paper. PMID- 6265310 TI - Leukotriene B4. PMID- 6265311 TI - Hypothalamic control of the pars distalis in fishes, amphibians, and reptiles. PMID- 6265312 TI - The influence of exogenous ACTH on the levels of corticosterone and cortisol in the plasma of young chicks (Gallus domesticus). PMID- 6265313 TI - [Induction of transposon Tn1 translocation in UV-irradiated Escherichia coli cells]. AB - Ampicillin transposon Tn1 translocates from plasmid RP4 into E. coli chromosome with a frequency of about 3.10(-4) per cell. Irradiation of bacteria with UV light increases the frequency of translocation essentially. Mutation in lexA gene controlling the expression of cell UV-inducible functions blocks the induction of transposon translocation. Protein synthesis inhibitor--chloramphenicol and transcription inhibitor--rifampicin decrease the effect of UV-light on transposition process. A possible mechanism of inducible transposition is discussed. PMID- 6265314 TI - [Transformation and transduction in Bacillus subtilis strains with the BsuR restriction-modification system by modified and unmodified pUB110 plasmid DNA]. AB - Plasmid pUB110 DNA is restricted and modified during transformation of Bacillus subtilis cells possessing the BsuR system of restriction-modification. Restriction has comparatively little influence on the frequency of plasmid transformation only reducing it 20 times. The frequency of transduction of nonmodified plasmid DNA into modifying recipient cells, using phage Ar9 is also reduced a little. The frequency of transduction of chromosomal markers is much more lowered under the same experimental conditions. PMID- 6265315 TI - Physical map of chloroplast DNA of Spirodela oligorrhiza; analysis by the restriction endonucleases PstI, xhoI, SacI. AB - Using the restriction endonucleases XhoI, SacI and PstI, physical maps of Spirodela oligorrhiza (duck weed) chloroplast DNA [with a relatively large m. wt. of 120 Md; see van Ee et al. (1980)] were constructed. The overall structural organization of S. oligorrhiza chloroplast DNA appears to be rather similar to that of chloroplast DNAs of other higher plants. It is composed of two invertedly repeated DNA segments of 17 Md, separated by a small single-copy region of 19 Md and a large single-copy region of 69 Md. Apparently the extra DNA (as compared with chloroplast DNAs of other higher plants) is present within the large single copy region. PMID- 6265316 TI - Functional analysis of hybrid plasmids carrying genes for lambda site-specific recombination. AB - A number of hybrid plasmids, carrying lambda genes involved in site-specific integrative recombination, have been constructed in vitro. Analysis of protein synthesis in Escherichia coli minicells has shown that Int protein is synthesized only when int gene is expressed constitutively. The plasmids RSF2124::lambda-CD, RSF2124::lambda-Cint-c57, and pInt lambda were able to integrate into the chromosome of E.coli at the attB. The integration of hybrid plasmids into the genome of bacteria has also been shown for polA1 strains restricting the autonomous replication of ColE1 type plasmids. Genetic markers of hybrid plasmids are maintained in polA1 bacteria for at least 50 generations under nonselective conditions. The Southern blotting experiments using [32P]pBR322 DNA and EcoRI fragments of E. coli polA1 chromosome carrying integrated plasmid pInt lambda demonstrated that in this strain hybrid plasmids can be observed only when integrated into the attB of the chromosome according to Campbell's model of integration. In the cells, where autonomous replication of plasmids is possible, they can be observed both in extrachromosomal and integrated states. The integration of the ColE1 replication origin into the chromosome of bacteria is not lethal for the cells. Only attP and the int gene of lambda are necessary for the integration of hybrid plasmids under conditions of effective int gene expression. If the level of Int protein synthesis is high enough, the prophage excision can be observed in the absence of Xis product. The six-fold decrease of Int protein concentration in the cell (in case of pInt lambda 2 as compared to pInt lambda 1) is critical both for integration and excision. PMID- 6265317 TI - Construction of plasmid vectors with unique PstI cloning sites in a signal sequence coding region. AB - We have constructed a series of plasmids with unique PstI restriction sites within or near the pre-penicillinase signal sequence for protein secretion. To do this, we devised a rapid, simple method to eliminate undesirable unique restriction sites within plasmids while maintaining antibiotic resistance. We thus obtained a plasmid with a conveniently located, unique HincII site in the penicillinase gene of plasmid pBR322 which was used to generate, with BAL 31 exonuclease, deletions extending into the region encoding the signal sequence. DNA inserted into these plasmids can be translated in all three reading frames both including signal sequence, or starting immediately beyond it. PMID- 6265318 TI - Cloning of mouse mitochondrial DNA in E. coli affects bacterial viability. PMID- 6265319 TI - The genetic code in bovine mitochondria: sequence of genes for the cytochrome oxidase subunit II and two tRNAs. AB - Bovine-heart mitochondrial DNA from a single animal was isolated and fragments representative of the entire genome cloned into multicopy plasmid vectors to facilitate determination of its complete nucleotide sequence. We present here the sequence of the region covering the gene for cytochrome oxidase subunit II. Comparison of this sequence with the amino acid sequence of the homologous beef heart protein has enabled the determination of most of the bovine mitochondrial genetic code. The code differs from the "universal" genetic code in that UGA codes for tryptophan and not termination, and AUA codes for methionine and not isoleucine. The only codon family not represented is the AGA/AGG pair normally used for arginine; evidence from other genes suggests that these code for termination in bovine mitochondria. The sequence presented also includes the adjacent tRNAAsp and tRNALys genes. The tRNAAsp gene is separated by one nucleotide from the 5' end of the COII gene and only three bases separate the 3' end of this gene and the adjacent tRNALys gene. This highly compact gene organisation is very similar to that found in the corresponding region of the human mitochondrial genome and the gene arrangement is identical. The structure of the respective bovine and human tRNAs vary primarily the "D-" and "T psi C loops". PMID- 6265320 TI - Single-strand and double-strand cleavage at half-modified and fully modified recognition sites for the restriction nucleases Sau3a and Taqi. AB - The influence of cytosine methylation on the cleavage of DNA by the restriction nucleases Sau3A and TaqI has been investigated. Bovine satellite DNA fragments containing a GATCGA sequence, i.e. a Sau3A site overlapping with a TaqI site have been used in this study. The methylation of these fragments has been determined by sequence analysis. It has been found that a TaqI site (TCGA) methylated at cytosine in both DNA strands is still sensitive to double-strand cleavage. A Sau3A site (GATC), however, is rendered resistant to double-strand cleavage by methylation of a single cytosine. Fragments containing the "half-modified" Sau3A site are nicked in the unmethylated DNA strand. It has been shown by sequence analysis of nicked DNA that the single-strand break occurs at the same position which is cleaved in unmodified DNA. PMID- 6265321 TI - IS5 increases recombination in adjacent regions as shown for the repressor gene of coliphage lambda. PMID- 6265323 TI - Construction of coliphage lambda Charon vectors with BamHI cloning sites. PMID- 6265322 TI - Molecular cloning of the gene (ush) from Escherichia coli specifying periplasmic UDP-sugar hydrolase (5'-nucleotidase). PMID- 6265324 TI - An analysis of the genome of actinophage phi EC. PMID- 6265325 TI - [Prediction of the degree of fibrogenicity of silica-containing dusts depending on the surface properties of the particles]. PMID- 6265326 TI - Aqueous solubilisation of vitamin D3 in normal man. AB - Jejunal aqueous solubilisation of vitamin D3 was assessed in eight normal subjects, after ingestion of a standard liquid test meal. Percentages and total concentrations of vitamin D3 in the aqueous phase were significantly higher in the first post-prandial 30 minutes than during the following two hours, as were bile salts, total lipids, and free fatty acids. As shown by partial correlation analysis, a statistically significant relationship was found between aqueous concentrations of free fatty acids and of vitamin D3 in the jejunal content during all the 2 1/2 hours of the study. From these data it is concluded that, in healthy man, vitamin D3 is solubilised in vivo in mixed micelles only, and is governed in the aqueous phase. PMID- 6265327 TI - Immunohistochemical evidence for prolactin in trophoblastic tumors. PMID- 6265328 TI - [isolation of viruses from the amniotic fluid in infections in early pregnancy]. PMID- 6265329 TI - Thymocyte maturation induced by a thymus-dependent serum factor. AB - By means of direct measurement of intracellular cyclic AMP in thymocytes in vitro we demonstrated the existence in human serum of a thymus-dependent factor (SF). This activity of SF appeared to be due to a very low M.W. (less than 500) peptide distinct from other circulating thymic peptides. SF was found to act selectively on immunologically immature, hydrocortisone (HC)-sensitive peanut lectin agglutinating thymocytes. In a period of 240 min SF sequentially induces in thymocyte synthesis of cyclic AMP, protein synthesis and synthesis of phosphorylated non-histone chromatin proteins of high molecular weight. Because SF does not induce a change in DNA synthesis, it seems likely that the events induced by SF are associated with a process requiring DNA translation, but not DNA replication. The biochemical events induced by SF are accompanied by the acquisition of immunological maturation by thymocytes. This has been shown by the acquisition of HC resistance, by the expression of FC receptors for IgM, by the decrease of terminal transferase activity and by the induction of the capacity to elicit a graft-versus-host reaction. We conclude that, most likely, SF acts on immature thymocytes inducing a part of them to acquire some properties of mature T cells. PMID- 6265330 TI - [Two families with Pendred's syndrome]. PMID- 6265331 TI - [Pre-operative staging of bronchial carcinomas: a comparison of computed tomography and conventional radiography (author's transl)]. AB - Pre-operative staging was carried out in 52 out of 112 patients suspected of having bronchial carcinomas, using computed tomography and conventional radiology. CT was superior in demonstrating tumour infiltration of the mediastinum, of the thoracic wall and of metastases in mediastinal lymph nodes. Conventional radiology was better for demonstrating intrabronchial tumour and metastases of bronchopulmonary lymph nodes. By extending CT to the upper abdomen, it was possible to show metastases in 18% of patients. PMID- 6265332 TI - [The sonographic appearance of the diffuse infiltrates stomach cancer (author's transl)]. AB - Using 5 cased of diffuse infiltrated stomach cancer we have described its characteristic sonographic appearance. We emphasize that sonography cannot replace endoscopic and x-ray measures, but it is a beneficial supplement. PMID- 6265333 TI - Chemodectoma, multiple localization: neck and mediastinum. PMID- 6265334 TI - [A biliary retention cyst. Diagnosis using ultrasonics and hepatobiliary sequence scintigraphy with 123I-iodoxamic acid]. PMID- 6265335 TI - [The influence of exogenous cyclic nucleotides and theophylline on the hydrokinetic and ecbolic function of the isolated perfused canine pancreas (author's transl)]. AB - The influence of exogenous cyclic nucleotides or theophylline either on basal or stimulated volume and protein secretion is studied on the isolated perfused canine pancreas in dependence on varied extracellular calcium concentrations. Bt2cAMP or theophylline do not influence basal secretory rates of pancreatic juice but potentiate secretin-stimulated volume output. They additionally increase basal protein secretion under exclusive secretin stimulation and potentiate dose-dependently CCK- or acetylcholine-induced protein output. The hydrokinetic and ecbolic effects of Bt2cAMP and theophylline persist in a calcium free medium but fail in normalizing inhibited protein secretion during calcium deprivation. Bt2cGMP neither increases basal nor stimulated volume and protein secretion. The demonstrated influence of Bt2cAMP and theophylline on ductal volume and acinar protein secretion accomplishes two criteria, as suggested by Sutherland, for cAMP as second messenger for secretin and CCK or acetylcholine as well. PMID- 6265336 TI - [Behavior of cellular cyclic nucleotides after hydrokinetic or ecbolic stimulation of the canine pancreas]. AB - The studies deal with the influence of secretin and various ecbolic secretagogues on tissue levels of cAMP and cGMP in vivo and in the isolated perfused canine pancreas. The mutual behaviour of cellular cAMP and cGMP is observed and compared with the time course of the respective secretory events. Synthetic secretin as well as CCK, acetylcholine or Caerulein likewise elevate tissue cAMP and cGMP simultaneously. There exists no difference in the magnitude of increase and in the time course of changes in tissue cyclic nucleotide levels between hydrokinetic and ecbolic stimulation. The rise in cAMP and cGMP coincides with the onset of the respective secretory events and reaches peak values contemporarily to the excretory maxima. The following decrease in tissue cyclic nucleotides approximatively parallels juice or enzyme secretion in the isolated perfused pancreas but differs widely in vivo. Under this condition cAMP and cGMP rapidly fall to basal levels during undiminished excretory function and show a second rise after cessation of the latter. Secretin and various ecbolic secretagogues do not increase tissue content of cyclic nucleotides in the same dose-dependent manner as can be observed with pancreatic secretion. The behaviour of cAMP and cGMP after addition of secretin and CCK or acetylcholine remains widely unchanged during calcium-free perfusion in spite of an extensive excretory inhibition. The corresponding rise in cellular cAMP and cGMP in the sequence of hydrokinetic as well as of ecbolic stimulation points to an analogous intracellular mediation of various secretagogues in different target cells of the exocrine canine pancreas. PMID- 6265337 TI - [The secretion of adenosin 3',5'-monophosphate after hydrokinetic and ecbolic stimulation in the canine pancreas (author's transl)]. AB - The secretion of cAMP is studied in vivo and in the isolated perfused canine pancreas after administration of secretin and CCK or caerulein in comparison with hydrokinetic or ecbolic secretory events as well as with the magnitude and time course of changes in tissue cAMP. 1) The total output of cAMP and pancreatic juice shows a significant and positive correlation after stimulation with secretin. The linear correspondence between cAMP concentration and secretory rates of pancreatic juice beyond 3 ml/5 min and their non-linear, reciprocal correlation at lower rates of fluid secretion point to an active as well as to a passive secretory mechanism for cAMP. 2) CCK and caerulein increase secretion of cAMP too. The output of cAMP however neither corresponds to the time course of protein secretion nor correlates quantitatively with the latter. 3) The behaviour of cAMP secretion and concentration in the pancreatic juice after administration of secretin and CCK or caerulein as well as differs from the changes in tissue cAMP levels. The respective maximum of cAMP output after addition of secretin or ecbolic secretagogues during the greatest decrease in cellular cAMP levels yields on the average about 1% of the estimated reduction in total tissue cAMP content. The results indicate a functional coherence in secretion of pancreatic juice and cAMP but oppose the assumption, that essential amounts of cAMP are released during exocytosis of zymogen granules. The secretion of cAMP may be possibly influenced by cytoplasmatic cAMP levels, but neither reflects the present changes in cellular cAMP nor seems to be of a regulatory importance for the latter. PMID- 6265339 TI - Lipids and membrane function: implications in arrhythmias. AB - Increasing attention is being devoted to the relevance of lipid-membrane interactions to arrhythmias and their therapy. Particular emphasis is placed on alterations of transmembrane ion transport that can result from closure of protein channels, perhaps mediated by chemically induced changes in the phospholipid membrane bilayer. Such alterations may underlie antiarrhythmic drug actions. PMID- 6265338 TI - Plasma catecholamines: effects of footshock level and hormonal modulators of memory storage. PMID- 6265340 TI - Giant cell pneumonia associated with parainfluenza virus type 3 infection. AB - Giant cell pneumonia associated with parainfluenza virus type 3 infection and chronic poliovirus type 2 meningoencephalomyelitis are documented in an infant with combined immunologic deficiency (Swiss type). Caution should be exercised in attributing cases of giant cell pneumonia to measles virus without serologic or virologic evidence. PMID- 6265341 TI - Genetics of Wilms' tumor. PMID- 6265342 TI - Adenylate kinase deficiency and malignant hyperthermia. AB - In a report of two patients who died of malignant hyperthermia, muscle adenylate kinase deficiency was identified in the father and brother of the deceased. To determine if this enzyme deficiency was a biochemical marker for susceptibility to malignant hyperthermia, we measured adenylate kinase in muscle of three survivors of malignant hyperthermia (MH) and five relatives of survivors of MH attacks with positive caffeine contracture tests. Neither the activity nor the electrophoretic mobility of adenylate kinase differed from four control values. The results show that muscle adenylate kinase deficiency is not a biochemical abnormality shared by all individuals susceptible to malignant hyperthermia. PMID- 6265343 TI - Novel multialveolar epithelial structures from rabbit mammary gland that synthesize milk specific fatty acids in response to prolactin. AB - Multialveolar mammary epithelial structures have been prepared from rabbit mammary gland by treating the tissue with collagenase plus hyaluronidase. These structures synthesize milk specific fatty acids when cultured with physiological concentrations (0.5 micrograms/ml) of prolactin in the presence of insulin and corticosterone. They have many of the advantages but few of the disadvantages of either mammary explants or primary cells in culture. For example, they are easily prepared in large numbers and respond to prolactin in culture even in the absence of serum or other tissue extracts. Because their level of organization is intermediate between that of explants and single cells, they provide a complementary system for studies on mammary differentiation. PMID- 6265345 TI - Purification & characterization of a nucleoside triphosphatase from Mimosa pudica. PMID- 6265344 TI - Stimulation of cyclic AMP production by vasoactive agents in cultured bovine aortic and pulmonary artery endothelial cells. AB - The ability of selected vasoactive agents to influence cyclic AMP levels of confluent, early-passaged bovine calf aortic and pulmonary artery endothelial cells was investigated. Among the agents tested, only the catecholamines (isoproterenol, epinephrine, norepinephrine) and prostaglandins (PGE1, PGE2, PGF2 alpha) resulted consistently in increased cyclic AMP production in both cell populations. The degree of cyclic AMP stimulation obtained with other vasoactive compounds (angiotensins I and II, bradykinin, and serotonin) tended to be either very small or difficult to reproduce. Isoproterenol stimulation was blocked completely by propanolol, a beta-blocking agent, but not by phentolamine, and alpha-blocking agent. These results reveal that bovine calf aortic and pulmonary artery endothelial cells are responsive to catecholamines and prostaglandins, and therefore presumably possess both sensitive adenylate cyclases and plasma membrane receptors for these compounds. PMID- 6265346 TI - Regulation of immune responses against the syngeneic ADJ-PC-5 plasmacytoma in BALB/c mice. I. Analysis of immune parameters involved. AB - The non-secreting variant of ADJ-PC-5 plasma cell tumour of BALB/c mice is a highly malignant tumor, the LD50 being 3 x 10(1) cells/mouse after intraperitoneal injection. Nevertheless, immunization against the tumour is possible. Four injections of 10(7) X-irradiated tumour cells at weekly intervals render up to 95% of mice resistant to an otherwise lethal challenge with 10(3) living tumour cells. The immune responses are both T cell-mediated cellular cytotoxicity and antibody-mediated cytotoxicity as assessed by in vitro tests. Immunity can also be transferred in vivo into recipient mice by either spleen cells or immune sera. Specificity of both types of immune responses was determined. The results indicate that the cell-mediated and the humoral immune response are directed against cell-surface antigens associated with endogenous murine leukemia virus. PMID- 6265347 TI - Sendai virus infected cells are readily cytolysed by guinea-pig complement without antibody. AB - HeLa cells infected with Sendai virus (SV) acquired the ability to activate the alternative pathway (AP) of guinea-pig complement without antibody reaction. For induction of complement activating ability (CAA), at least 2 hr incubation of the infected cells was required. However, ultraviolet (UV)-irradiation (8400 erg/mm2) of SV did not impair the inducibility of CAA and 51Cr-labelled HeLa cells infected with UV-irradiated SV (UV-SV) became readily cytolysed by C4-deficient guinea-pig complement without antigen-antibody reaction. This phenomenon may represent a primary in vivo defence mechanism against SV infection by eliminating the virus-infected cells via activation of complement on the cell surface. Although SV-infected HeLa cells activated the AP of guinea-pig complement, they did not activate the AP of human or mouse complement. The species restriction in the CAA induced by SV infection may result in different pathological manifestations in virus-infected animals and may affect their susceptibility to this type of infection. PMID- 6265349 TI - Bronchial adenoma. PMID- 6265350 TI - Malignant transformation in antecedent mixed parotid tumour. PMID- 6265348 TI - Tolerance and immunity in mice infected with herpes simplex virus: studies on the mechanism of tolerance to delayed-type hypersensitivity. AB - Tolerance to delayed-type hypersensitivity is produced in mice following an intravenous injection of herpes simplex virus. This form of tolerance is produced early on, following simultaneous injections of virus subcutaneously and intravenously, and is long lasting (greater than 100 days). The early tolerance mechanism is resistant to high doses of cyclophosphamide and is not transferable by serum or spleen cells taken after 7 days. However, spleen cells taken at 14 days onwards inhibit the induction of delayed hypersensitivity when transferred to normal syngeneic recipients. These cells are T lymphocytes and are specific for the herpes type used in the induction. PMID- 6265352 TI - Inapparent infection by Japanese encephalitis (JE) virus in West Bengal. PMID- 6265353 TI - Klippel Trenaunay Weber syndrome: an unusual presentation as prolonged post traumatic bleeding. (Case Reports). PMID- 6265354 TI - [Hepatic scintigraphy]. PMID- 6265351 TI - Steroidogenic characteristics of a new aldosterone-stimulating factor (ASF) isolated from normal human urine. AB - The steroidogenic properties of a glycoprotein fraction (urinary ASF), isolated from normal human urine, were studied in collagenase-dispersed rabbit adrenal capsular cells in 1) define the requirements for its steroidogenic activity, and 2) assess its site and mode of action. When incubated with adrenal cell suspension at 37 degrees C for 2 hours, urinary ASF induced dose-related increases in both aldosterone and corticosterone production. However, urinary ASF was less potent (ED50 = 10(-9) M) than either angiotensin II (ED50 = 8 x 10(-11) M) or ACTH (ED50 = 4 x 10(-11) M). Increases in cyclic AMP accompanized the steroidogenic response to ACTH but not to either urinary ASF or AII. Deprivation of potassium in incubation media or the addition of ouabain (1 mM) during incubation completely inhibited the steroidogenic response to either urinary ASF, ACTH, or AII. Like ACTH and AII, urinary ASF increased conversion of corticosterone to aldosterone. Specific competitive antagonist of AII (Sar1, Thr8, AII) and ACTH ([I1e9]ACTH1-24) did not prevent the ASF-induced increase in aldosterone production. These results suggest that urinary ASF is readily distinguishable from ACTH. Although it shares similar steroidogenic properties with AII, the inability of AII antagonist to block its effects suggests that it acts at a separate receptor site. PMID- 6265357 TI - Cell-produced viral inhibitor: possible mechanism of action and chemical composition. AB - A newly recognized cell-produced viral inhibitor appeared to be spontaneously released from most cells in tissue culture. It strongly inhibited the replication of a variety of viruses but did not exhibit species specificity as does interferon. These studies on the inhibitor's mechanism of action indicated that it inhibited attachment and penetration of virus by a readily reversible reaction requiring the presence of both virus and cells. Studies of inactivation by specific enzymes or chemicals indicated that for activity the inhibitor required intact protein but not lipid, carbohydrate, deoxyribonucleic acid, or ribonucleic acid. PMID- 6265355 TI - Some enzymatic characteristics of eosinophil peroxidase from patients with eosinophilia and from healthy donors. AB - Some enzymatic characteristics of human eosinophil peroxidase were compared with those of human myeloperoxidase. Both enzymes catalyzed the oxidation of iodide by hydrogen peroxide. This assay proved to be very sensitive; the activity of 100 eosinophils/ml could be measured. The position of the pH optimum of this reaction was linearly dependent on the logarithm of the iodide/H2O2 ratio. At the same substrate ratio, this optimum was about 1 pH unit higher for eosinophil peroxidase than for myeloperoxidase. This difference may be related to the action of myeloperoxidase inside an acidified phagolysosome as opposed to the extracellular action of eosinophil peroxidase on the surface of certain parasites. Under defined conditions (KI, 1.4 mM; H2O2, 0.18 mM; cetyltrimethylammonium bromide, 0.008% [wt/vol]; pH 6), the activity of eosinophil peroxidase could be measured in a mixed granulocyte suspension independently of myeloperoxidase. Eosinophils from patients with eosinophilia were found to contain as much peroxidase activity as did eosinophils from healthy donors. No enzymatic differences in eosinophil peroxidase were found between the two types of donors. PMID- 6265356 TI - Broadly active inhibitor of viruses spontaneously produced by many cell types in culture. AB - A broadly active inhibitor of viruses (vaccinia, polio 1, and vesicular stomatitis) was found in the culture fluid from many types of normal human and mouse cells in culture. Virus plaque-inhibiting activity appeared in culture fluids within a few hour after incubation of cultures with fresh medium. Peak inhibitory activity occurred within 24 h. Blockade of cellular ribonucleic acid or protein synthesis decreased appearance of the inhibitor, thereby substantiating that it is a cell-produced viral inhibitor. Inhibition of virus required the simultaneous presence of inhibitor, virus, and cells (due to the reversible nature of the inhibition of virus attachment and penetration, as shown in the accompanying paper [T. K. Hughes et al., Infect Immun. 32:454-457, 1981]). The degree of inhibitory activity depended on the animal species of origin of the inhibitor, the cell type used for assay, and the virus type used for challenge. No cell species barrier against inhibitor action was found. Strong inhibition of multicycle yields of vesicular stomatitis virus and Sindbis virus was caused by low doses of inhibitor. These specific characteristics of the present inhibitor separate it from commonly recognized inhibitors. Possible biological significance of the inhibitor is discussed. PMID- 6265358 TI - Specificity and reversibility of chemotactic deactivation of human monocytes. AB - The chemotactic deactivation of human monocytes was studied to provide insight into the mechanism of chemotaxis. Deactivation was dependent on the dose of chemoattractant and time of incubation. A concentration in the cell suspension of 10(-8) M N-formylmethionylleucyl phenylalanine (FMLP) for 45 min at 37 degrees C led to 60% suppression of the subsequent specific chemotactic response. Higher concentrations of FMLP led to almost 100% specific suppression. Deactivation was specific under all conditions used. The response to a nonrelated chemoattractant, human serum-derived C5a, was unaffected by incubation in FMLP. Deactivation was also transient. If cells were deactivated at 37 degrees C with FMLP, they recovered within 6 h at 37 degrees C from this deactivation. Both phenomena, deactivation and recovery from deactivation, were temperature dependent. Monocytes could not be deactivated at 0 degrees C, and they did not recover from deactivation when kept at 0 degrees C. Thus, specific deactivation appears to require cellular metabolism, involving loss of receptors or blocking of a step between receptor occupancy and response. PMID- 6265359 TI - Elicitation of anti-vesicular stomatitis virus cytotoxic T lymphocytes by using purified viral and cellular antigens incorporated into phospholipid vesicles. AB - We evaluated the minimal molecular and cellular requirements for elicitation of anti-vesicular stomatitis virus (VSV) cytotoxic T lymphocytes (CTL). The results indicated that lipid vesicles containing the purified major surface glyco-protein of VSV (G protein) and purified H-2K(k) glycoproteins elicited specific H-2K(k) restricted anti-VSV CTL. These antiviral CTL were shown to be Ly 1(-),2(+). However, both Ly 1(+),2(-) and Ly1(-),2(+) T-cell subpopulations were shown to be required for elicitation of these CTL. PMID- 6265360 TI - Infection of multiple T-cell subsets and changes in lymphocyte functions associated with Herpesvirus saimiri infection of owl monkeys. AB - We examined the association of Herpesvirus saimiri with lymphocyte subsets and the functional integrity and distribution of these populations in owl monkeys with chronic, disease-free infections, in uninoculated, control animals, and in one monkey with H. saimiri-induced lymphoma. The lymphocyte subpopulations examined included total T cells, T cells with receptors for the Fc portion of immunoglobulin G (the Tgamma cells), T cells lacking this receptor (the Tgamma(-) population), and non-T cells. These studies showed that in chronically infected monkeys, H. saimiri was found in both Tgamma and Tgamma(-) populations and that the relative distribution of lymphocyte subsets was not different than the relative distribution in normal animals. The peripheral blood of the one leukemic animal studied showed an increase in total T cells, and both Tgamma and Tgamma(-) cells were increased in number and contained recoverable H. saimiri. In animals with chronic infections, which previously were thought to be immunologically normal, we showed that the Tgamma cells had lost the ability to respond to phytohemagglutinin. When the level of nonspecific cytotoxic activity was examined, we found that the lymphocytes from infected animals were as active as those from uninfected monkeys and that this activity was maintained at normal levels during disease. In the leukemic blood there was a relative increase in the cytotoxic activity of the Tgamma(-) cells. The Tgamma(-) cells obtained from leukemic blood lacked the ability to respond to phytohemagglutinin and could suppress the phytohemagglutinin response of normal cells. This suppressor cell activity was resistant to 3,000 rads of X irradiation. We also found that cells reactive to H. saimiri antigens could be demonstrated in the lymph nodes but not in the peripheral circulation of the lymphomatous monkey. PMID- 6265361 TI - Analysis of avian leukosis virus infections with an enzyme immunoassay. AB - An enzyme-linked immunosorbent assay (ELISA) for avian leukosis virus group specific antigen was used to study infections with and shedding of avian leukosis virus in a commercial flock of chickens with a known high incidence of infection. Avian leukosis virus group-specific antigen was detected in serum or cloacal washings from 76% of a group of 100 61-week-old hens. With eggs collected during the next 3 weeks, antigen was detected in the albumen of 88% of the eggs from ELISA-positive hens and 2% of the eggs from ELISA-negative hens. Results of assays for infectivity correlated closely with the ELISA results. Serum and cloacal specimens were almost equally sensitive in detecting infection; however, a higher proportion of cloaca-positive hens (97%) than serum-positive hens (91%) shed virus in their eggs. Similar results were obtained from a second sampling of eggs taken when the hens were 84 weeks old, after an intervening molt. Avian leukosis virus infection was correlated with reduced egg production and increased mortality. Eggs were produced by 100% of the ELISA-negative birds during both sampling periods, whereas only 69% of the ELISA-positive birds produced eggs at 61 weeks and 76% produced eggs at 84 weeks. All birds that were ELISA negative at 61 weeks survived the experiment. Of 14 ELISA-positive birds that died and were examined postmortem between 61 and 84 weeks, 8 had malignancies, and the remainder died of a variety of nonmalignant diseases. PMID- 6265362 TI - Influence of yeast mannan on human neutrophil functions: inhibition of release of myeloperoxidase related to carbohydrate-binding property of the enzyme. AB - We investigated the possibility that dissolved mannan polysaccharide from Candida may have an inhibitory influence on the host defense mechanisms associated with neutrophils and thereby contribute to the pathogenesis of candidoses. We created a model for this hypothesis by using mannan derived from bakers' yeast (Saccharomyces cerevisiae) and mannan isolated from the serum of a patient with chronic mucocutaneous candidosis. We observed that these mannans inhibited the respiratory burst and release of myeloperoxidase stimulated by phagocytosis of serum-opsonized zymosan in vitro. Mannan did not inhibit release of three other lysosomal enzymes. The selective inhibition of release of myeloperoxidase was attributable to a carbohydrate-binding property of the enzyme, with the mannan causing co-sedimentation of the enzyme with the cellular fraction. PMID- 6265363 TI - Effect of formalin toxoiding on Pseudomonas aeruginosa toxin A: biological, chemical, and immunochemical studies. AB - We investigated the effect of Formalin toxoiding on the biological, chemical, and immunological activities of Pseudomonas aeruginosa toxin A. Formalin treatment alone resulted in a 1,000-fold decrease in toxin-induced cell cytotoxicity and altered the antigenicity of the toxin A molecule without adversely affecting enzymatic activity. Competitive blocking experiments indicated that Formalin mediated detoxification proceeded via alterations in a region of the toxin molecule other than the active site of the enzyme. The addition of lysine to Formalin-toxin mixtures not only increased the rate and extent of detoxification and antigenic alteration, but also completely destroyed enzymatic activity. The immunogenicities of different toxoids varied substantially. Upon dialysis and storage, Formalin-derived toxoids underwent partial toxic reversion, whereas a Formalin-lysine-derived toxoid did not. The sodium dodecyl sulfate-polyacrylamide gel patterns of Formalin- and Formalin-lysine-treated toxins indicated that these treatments caused the formation of a heterogenous group of high-molecular-weight species and produced substantial changes in the electrophoretic mobility of toxin A. PMID- 6265364 TI - Biochemistry of Theiler's murine encephalomyelitis virus isolated from acutely infected mouse brain: identification of a previously unreported polypeptide. AB - The WW strain of Theiler's murine encephalomyelitis virus (WW-TMEV) was purified from homogenates of acutely infected mouse brain. Infectious WW-TMEV was found to have an estimated sedimentation coefficient of 156 (s20,w) and a density of 1.35 g/cm3 in CsCl. Electron microscopy revealed a homogeneous population of 26-nm nonenveloped particles. Iodination of sodium dodecyl sulfate (SDS)-disrupted virions revealed four major capsid proteins with molecular weights of 58,000, 37,000, 34,000, and 27,000. A 6,000-dalton polypeptide was observed after long exposures of autoradiograms. The 37,000-, 24,000-, 27,000-, and 6,000-dalton polypeptides corresponded to picornaviral VP1, VP2, VP3, and VP4 capsid polypeptides, respectively. Comparison of autoradiograms of virions radiolabeled before and after SDS disruption indicated that the 58,000-dalton protein, VP2, and VP3 preferentially bound 125I under the labeling conditions used. Direct evidence was obtained that VP2 and VP3 were derived from the 58,000-dalton polypeptide by isolation of the 58,000-dalton polypeptide from polyacrylamide gels run under nonreducing conditions and subjecting it to reelectrophoresis under reducing conditions. The effect of trypsin on purified virions and their polypeptides was also investigated. Trypsin-sensitive sites were found in the 58,000-dalton protein, VP1, and VP2. Our results indicate that, in addition to the four typical picornaviral capsid polypeptides, there is a 58,000-dalton polypeptide present in WW-TMEV, which is sensitive to trypsin and can be reduced into two of the capsid proteins, VP2 and VP3. PMID- 6265365 TI - Antibody to human adenovirus early antigens during acute adenovirus infections. AB - The antibody (Ab) response to human adenovirus (AV) early antigens (EA) in acute AV infections was studied by the immunoperoxidase antibody technique for determining virus-specific immunoglobulin G (IPA-IgG). AV-EA-Ab appeared about 5 days after the onset of clinical symptoms, reached a peak 15 to 30 days later, and declined in titer after a few months. The staining pattern in the IPA-IgG reaction was usually nuclear; however, in most primary infections sera obtained 2 to 3 weeks after the onset of infection also showed cytoplasmic staining. According to the recent deoxyribonucleic acid homology classification of human AV in five groups (A, B, C, D, and E), the EA-Ab response in primary human infections was found to be group specific for groups A to D, with consistent cross-reactions with group E. In AV type 4 (group E) infections, EA-Ab appeared to be directed against all groups, although at different titers. Comparable results were obtained using AV type-specific animal antisera. Thus, it was concluded that group E shares EA with all the other groups. Furthermore, in each individual with remote AV infections, the current infection elicited an anamnestic EA-Ab response to all AV groups responsible for previous infections. In diagnostic virology these findings can be applied to the rapid diagnosis of a current for recent) AV infection on a single serum sample and to the rapid group identification of clinical isolates by using type-specific animal antisera containing EA-Ab (one for each group) or sera from patients with primary AV infections. PMID- 6265367 TI - Pathogenesis of a pichinde virus strain adapted to produce lethal infections in guinea pigs. AB - A model for studying the pathogenesis of virulent arenavirus infection was developed by adapting Pichinde virus to produce lethal infections of inbred guinea pigs. This adapted Pichinde virus retained low virulence for primates, thus potentially reducing the biohazard to investigators. Whereas all inbred (strain 13) guinea pigs were infected and killed by 3 plaque-forming units or more of adapted Pichinde virus injected subcutaneously, outbred (Hartley strain) guinea pigs were relatively resistant. All infected, inbred guinea pigs died at 13 to 19 days after inoculation, with viremias in excess of 5 log(10) plaque forming units/ml, severe lymphopenia (<1,000/mm(3)), and elevated serum glutamic oxaloacetic acid transaminase levels. Immunofluorescent antibody examination of tissues and infectivity titrations of tissue homogenates obtained at 3- to 4-day intervals demonstrated significant viral replication in all visceral tissues examined, but not in brain. Livers of all moribund guinea pigs contained moderate to severe hepatocellular necrosis and diffuse fatty change. Splenic red pulp and adrenal cortical tissues were engorged with blood and contained necrotic foci. Pancreatic acinar tissues were atrophied and vacuolated; lung sections typically contained areas of moderate to severe interstitial pneumonia. Inflammatory cells were conspicuously absent from all lesions. The virological and pathological features of adapted Pichinde infection in guinea pigs are remarkably similar to those described for Lassa virus infections in rhesus monkeys and humans, suggesting that this model might provide insight into the pathogenesis and treatment of Lassa fever in humans. PMID- 6265366 TI - Cytomegalovirus-induced mononucleosis in guinea pigs. AB - The effects of cytomegalovirus (CMV) infection on hematopoietic and lymphoid tissues were studied in guinea pigs. Blood parameters, histopathology, and virus distribution in the bone marrow, spleen, lymph nodes, and thymus were assessed during primary nonlethal acute and chronic guinea pig CMV infection. Transient hematological changes comparable to those seen in human CMV mononucleosis were observed during acute infection. These included anemia and leukocytosis with atypical lymphocytes. Splenomegaly and stimulation of spleen and lymph node T- and B-cell areas were also noted. These changes occurred at the peak of virus recovery from all tissues tested, as well as from macrophages and B- and T- cell enriched spleen subpopulations. Virus was cleared rapidly from blood and bone marrow; blood counts, spleen size, and histology returned to normal within 1 month after virus inoculation. However, guinea pigs failed to eliminate the virus completely from lymphoid tissues, since virus persisted in splenic macrophage and B-lymphocyte-enriched populations during chronic infection. The data suggest that CMV-infected mononuclear cells play a role in the establishment of generalized acute infection and virus persistence. PMID- 6265368 TI - Model for studying bacterial adherence to epithelial cells infected with viruses. AB - Measles infection decreased adherence of staphylococci, streptococci, and pneumococci to cultured epithelial cells, whereas adenovirus had no effect. Rhinovirus increased staphylococcal and streptococcal adherence. Influenza A increased or decreased staphylococcal adherence at different times after infection. PMID- 6265369 TI - Genetic analysis of resistance to lethal infections of vesicular stomatitis virus in Syrian hamsters. AB - Vesicular stomatitis virus (VSV), Indiana serotype, causes a lethal disease in adult Syrian hamsters. Susceptibility to low doses of VSV (10 to 100 plaque forming units) was shown to be genetically determined by examining six inbred strains. Three strains, LSH, MHA, and CB, were found to be extremely susceptible, with more than 70% of the animals dying within 72 h after intraperitoneal injection. Two strains, MIT and UT2, were intermediately susceptible, with approximately 60% of VSV-infected animals surviving. One strain, UT1, was found to be highly resistant; however, resistance was not acquired until the 4th or 5th week of age, and 100% of VSV-infected neonatal hamsters died. Analyses of F1 hybrid and segregant backcross populations derived from the LSH and UT1 strains suggested that at least three independent genetic loci contribute to phenotypic resistance. One locus resides on the X chromosome; the others reside on autosomes. No obvious linkage to the hamster major histocompatibility complex was detected. F1 hybrids of two highly susceptible strains, CB and MHA, were more resistant than either parental strain, suggesting that alleles of unlinked genes in the susceptible strains interact to produce a partially resistant phenotype. These alleles probably are the cause of the resistance phenotype found in the random-bred LVG strain which shares a common heritage with the CB and MHA strains. PMID- 6265371 TI - Murine cytomegalovirus infection in the spleen and its relationship to immunosuppression. AB - An attempt was made to correlate murine cytomegalovirus-induced immuno suppression with the presence of virus-infected cells in the spleen. For this purpose, SWR/J mice were infected with murine cytomegalovirus, and spleens were removed periodically and assayed for the presence of infectious centers in different cell populations and for their capacity to respond to mitogens. The maximal degree of immunosuppression correlated with the peak in adherent cell infectious centers. This was followed by a rapid rise in the number of cells per spleen (splenomegaly), a more gradual return to normal responsiveness to mitogens, and a rapid disappearance of infectious centers. These results add more support to the hypothesis that murine cytomegalovirus-induced immunosuppression is caused indirectly by infection of adherent spleen cells. PMID- 6265370 TI - Replication of vesicular stomatitis virus in mouse spleen cells. AB - Mouse spleen cells which normally cannot support the in vivo replication of vesicular stomatitis virus (VSV) became susceptible to VSV infection after the intraperitoneal growth of certain syngeneic and allogeneic tumors. After 3 days' growth of P815 tumor cells in syngeneic DBA/2 mice, the viral-permissive state for VSV replication had been established. By 7 days after tumor in inoculation, up to 18% of the spleen cells were producing virus yielding greater than 10(8) plaque-forming units per spleen. Similarly, P815 cells induced the viral permissive state in allogeneic C3H/HeN mice. Tumors other than P815 were also effective in permitting VSV growth in the spleen. The presence of tumor cells themselves was not sufficient for VSV growth, yet cell-free ascitic fluid from mice bearing syngeneic tumors inoculated 3 h before infection allowed for VSV replication. Cell-free supernatant from a T-cell hybridoma synthesizing interleukin-2 was also effective in permitting virus growth when inoculated 3 h before infection. The virus-permissive cell has been characterized as a nylon wool-adherent and plastic dish-nonadherent spleen cell. PMID- 6265372 TI - Transposon-facilitated recombination in classical biotypes of Vibrio cholerae. AB - Transposon-facilitated recombination (Tfr) donors of classical Vibrio cholerae strain 162 were constructed by introducing the ampicillin transposon Tn1 into the P conjugative plasmid and the bacterial chromosome. The improved donors mediated high-frequency, polarized transfer of chromosomal genes from origins to confirm the gene orders of the previous classical strain 162 genetic map and to establish its circularity. Significant transfer of linked genes from E1 Tor Tfr donors to classical recipients was demonstrated, and other evidence for genetic relatedness of these two V. cholerae biotypes is discussed. PMID- 6265373 TI - Initiation of the respiratory burst of human neutrophils by influenza virus. AB - The role of the oxygen-dependent microbicidal systems of polymorphonuclear neutrophils in virus inactivation is not known. We found that isolated neutrophils responded to incubation with purified influenza virus A particles by consumption of oxygen, generation of chemiluminescence, and production of superoxide; these reactions occurred in the absence of serum. Resting leukocyte oxygen consumption doubled in the presence of virus; the average rate of consumption 2 to 12 min after virus was added was 1.54 nmol/10(7) cells per min. Live virus also stimulated superoxide production in a dose-dependent manner at a rate up to 4.54 nmol/10(7) cells per min. Luminol-amplified chemiluminescence was a rapid dose-dependent reaction which peaked 2 to 4 min after live or ultraviolet light-inactivated virus was added. No light was emitted when heat-inactivated virus particles were used, suggesting that heat-labile factors on the virus envelope may be involved in oxidative stimulation. Virus-stimulated neutrophils from a patient with chronic granulomatous disease emitted no light. The evidence that virus initiated the respiratory burst of neutrophils provided a potential mechanism for virus destruction, either by direct intracellular inactivation or by neutrophil-mediated cellular cytotoxicity of virus-infected target cells. PMID- 6265374 TI - Measurement of 5'-nucleotidase in mouse peritoneal macrophages in listeriosis. AB - 5'-Nucleotidase activity in peritoneal macrophages of mice was measured both before and after infection with Listeria monocytogenes in hosts which possessed high or low anti-listerial resistance either due to a genetically determined trait or as a result of splenectomy. Reduction in enzyme activity was directly related to the degree of infection that developed in the hosts and hence was inversely related to the level of anti-listerial resistance observed. Basal 5' nucleotidase activity was significantly lower in noninfected hosts that possessed high anti-listerial resistance, possibly reflecting a higher level of native macrophage activation in these hosts. PMID- 6265375 TI - Psoralen inactivation of influenza and herpes simplex viruses and of virus infected cells. AB - Psoralen compounds covalently bind to nucleic acids when irradiated with long wavelength ultraviolet light. This treatment can destroy the infectivity of deoxyribonucleic acid and ribonucleic acid viruses. Two psoralen compounds, 4' hydroxymethyltrioxsalen and 4'-aminomethyltrioxsalen, were used with long wavelength ultraviolet light to inactivate cell-free herpes simplex and influenza viruses and to render virus-infected cells noninfectious. This method of inactivation was compared with germicidal (short-wavelength) ultraviolet light irradiation. The antigenicity of the treated, virus-infected, antigen-bearing cells was examined by immunofluorescence and radioimmunoassay and by measuring the capacity of the herpes simplex virus-infected cells to stimulate virus specific lymphocyte proliferation. The infectivity of the virus-infected cells could be totally eliminated without altering their viral antigenicity. The use of psoralen plus long-wavelength ultraviolet light is well suited to the preparation of noninfectious virus antigens and virus antigen-bearing cells for immunological assays. PMID- 6265376 TI - Oligonucleotide fingerprinting of ribonucleic acids of infectious bronchitis virus strains. AB - A total of 11 distinct oligonucleotide fingerprints were obtained in studies of the ribonucleic acids of 13 isolates of infectious bronchitis virus. Different serotypes had distinct fingerprints, but so did varieties within a serotype, allowing a greater degree of strain differentiation than was previously possible. Some conclusions can be drawn from the fingerprints concerning theories of origin and spread of infectious bronchitis virus. PMID- 6265377 TI - Role of macrophages in resistance of mice to experimental cryptococcosis. AB - Mice with either a stimulated or depressed reticuloendothelial system were used to study the role of macrophages in resistance to experimental Cryptococcus neoformans infection. Silica, administered intravenously to destroy macrophages, considerably decreased the phagocytic index of the reticuloendothelial system as determined by a carbon clearance test. Silica given 1 day before intravenous challenge with 5 X 10(3) (1 50% lethal dose) of C. neoformans markedly decreased the resistance of mice to cryptococcal infection. Mice given repeated doses of BCG to nonspecifically activate their macrophages could withstand a challenge of 100 50% lethal doses of C. neoformans. These results provide evidence that macrophages play an essential role in natural or nonspecific cell-mediated immunity to murine cryptococcosis. PMID- 6265378 TI - Isolation of allergenically active cytochrome c from Kentucky blue grass pollen. AB - An allergen, designated as Kentucky blue grass KBG-cytochrome c, was isolated from the nondialysable constituents (R) of the aqueous extract of KBG pollen by a combination of gel filtration and preparative isoelectrofocussing techniques. The allergen had an absorption spectrum characteristic of heme protein and had a molecular weight corresponding to 12,000 daltons. It was a basic protein with a pI value of 9.9 and contained all the common amino acids. KBG-cytochrome c elicited immediate hypersensitivity cutaneous reactions in individuals allergic to KBG pollen. PMID- 6265379 TI - Effect of low doses of alpha chlorohydrin on the enzymes of glycolytic and phosphogluconate pathways in the rat testis and epididymis. AB - A biochemical study has been made of the effects of low doses of alpha chlorohydrin on all the glycolytic enzymes and two key enzymes of phosphogluconate pathway i.e. glucose-6-phosphate dehydrogenase (G-6-PDH) and 6 phosphogluconate dehydrogenase (6-PGDH) of rat testis and epididymis. All the glycolytic enzymes of testis and epididymis are decreased after treatment with alpha chlorohydrin. G-6-PDH and 6-PGDH are decreased only in epididymis and not in the testis. LDH, ADH and glucose-6-phosphatase were also studied histochemically to show that the drug affects the glycolytic enzymes of epididymal cells and various testicular cell types of testis. Possible significance of these results is discussed. PMID- 6265380 TI - Sperm suppression with monthly injections of medroxyprogesterone acetate combined with testosterone enanthate at a high dose (500 mg). AB - The combination of an initial injection of 1000 mg of depot medroxyprogesterone acetate and 500 mg of testosterone enanthate, followed by monthly administration of 150 mg and 500 mg of the same drugs, was tested in 10 healthy males aged 28 through 39, with pre-treatment sperm counts of 50 x 10(6)/ml or more. Eight of the subjects achieved azoospermia, and the sperm counts of the other two declined 0.09 ad 5 million/ml. This last subject was highly refractory to treatment as his sperm density recovered to 27 million sperm/ml at the 6th month of continuous therapy. FSH was severely depressed during the entire treatment period. LH fell to 30--40% of normal values in the first two months and then showed a slow recovery during maintenance treatment. Testosterone measured one month after each injection was between 10 and 30% of pre-treatment values. Three of the subjects had increased libido and potency, none had decreased sexual drive or potency. All subjects gained weight with the average gain being 6 kg. The increase in the dose of testosterone enanthate to 500 mg/ng did not improve the results as compared to previous trials using lower doses of TE. PMID- 6265381 TI - Stimulated VLF-fields as a risk factor of thrombosis. PMID- 6265382 TI - Herpesvirus saimiri: protective effect of attenuated strain against lymphoma induction. AB - An attenuated strain of Herpesvirus saimiri (A-HVS) induced a persistent, latent infection in common marmosets. Virus was recovered from circulating lymphocytes of infected animals and antibody response to virus-specified antigens was demonstrated over 3-12 months PI. A-HVS-infected common marmosets and animals without previous A-HVS exposure were challenged with oncogenic HVS (125-825 PFU); marmosets without A-HVS infection developed malignant lymphoproliferative disease and died 3 weeks PI whereas all persistently-infected animals have survived 38-43 months post challenge. PMID- 6265383 TI - The role of gp70 in the target antigen recognized by murine leukemia virus immune cytotoxic T-lymphocytes. PMID- 6265384 TI - Colony morphology, cell growth and viral radiosensitivity as parameters for detecting strain differences in Epstein-Barr virus (EBV). AB - Several parameters of two lymphocyte-transforming Epstein-Barr viruses (EBVs), B95-8 and Olare, derived from infectious mononucleosis (IM) and African Burkitt's lymphoma (BL), respectively, were compared to determine if there were biological differences between Epstein-Barr viral strains. Morphology of transformed colonies, growth of transformed cell lines, sensitivity to UV light and X irradiation, as well as EBV-related, antigens were investigated in autochthonous cell lines. The morphology of transformed colonies was found to differ consistently both in new transformants and in lines which had been continuously growing in culture for almost 1 year. The BL transformants grew to greater density than did the IM transformants, and BL-derived virus was more sensitive to both UV light and X-irradiation. No immunologic differences were noted in the strains in assays performed for EBV-related antigens. PMID- 6265386 TI - Hormones, chemicals and proviral gene expression as contributing factors during mammary carcinogenesis in C3H/StWi mice. PMID- 6265385 TI - Epstein-Barr virus-induced malignant lymphoma in a white-lipped marmoset. AB - One of six white-lipped marmosets inoculated with cell-free B95-8 virus developed diffuse malignant lymphoma. Epstein-Barr virus (EBV) DNA was detected in a pathologically enlarged mandibular lymph node by DNA-DNA hybridization. The affected animal at the time of killing had EBV antibody titers of 1:320 for viral capsid antigen (VCA) and 1:20 for early antigen (EA) while all non-diseased animals had less than or equal to 1:80 VCA antibody and no detectable EA antibody. This is the first report of lymphoma development in a white-lipped marmoset following EBV inoculation. PMID- 6265387 TI - Induction of type-C retrovirus by the tumor promotor TPA. AB - The tumor promotor 12-0-tetradecanoyl-phorbol-13-acetate (TPA) induced endogenous murine xenotropic type-C retrovirus from A1-2 cells, derived from the BALB/c mouse, as determined by infectious center focus-forming assay on permissive normal rat kidney (NRK) cells. Kinetic dose-response studies showed that the number of cells induced to release virus was dependent on TPA concentration and the time of assay following TPA exposure. Maximal induction occurred when cells were treated with 80 ng/ml of TPA for 24 h and assayed at 24 or 48 h. A 30-min pulsed TPA exposure and 200 ng/ml induced virus levels approximating those observed after a continuous 24-h exposure to 80 ng/ml. The combination of TPA at concentrations of 10 and 20 ng/ml and a suboptimal level of 5-iodo-2-deoxyuridine (IdUrd) enhanced retrovirus induction threefold above that seen by the optimum IdUrd concentration alone. The protease inhibitors, antipain and leupeptin, decreased virus induction by TPA, a protease inducer. The capacity of TPA to induce type-C retrovirus complements results demonstrating the enhancement of Epstein-Barr virus (EBV) and murine mammary tumor virus (MMTV) synthesis by TPA. PMID- 6265389 TI - Protective effect of zeolite absorbed Trypanosoma gambiense inactive vaccines on mice. AB - Inactive T. gambiense vaccines treated with strong absorbent natural zeolite and kept at 4 degrees C for 3 days were injected into mice. After 2 weeks, 75% of the white mice which had received single injection survived, 85% of double injections survived challenge with 100 parasites separated from T. gambiense-infected mouse blood. However, the survival rats of the inoculated mice challenged after 3 weeks were 55% (one injection) and 80% (two injections) respectively. The mice were challenged 2 weeks after they were inoculated with vaccines made in the same way as mentioned above except that the prepared time was lengthened to 6 days. The total survival rates were 67.4% (one injection) and 85% (two injections) and these challenged 3 weeks after inoculation were 50% (one injection) and 80% (two injections). Mice not surviving in the experimental groups lived longer by 3--4 days than those in the controlled ones which had no survivors at all. Inactive vaccines prepared with artificial zeolite showed little protective effect on mice. PMID- 6265390 TI - Active perfringocin typing of food poisoning strains of Clostridium perfringens type A--a new tool for epidemiological investigations. AB - Active perfringocin typing, as an epidemiological tool, for investigation into food poisoning outbreaks due to C. perfringens type A has been developed. Ninety strains included in this study were from England, America, India, Japan, France and Canada Nine indicator strains exhibiting different patterns of inhibition were selected for perfringocin typing. With these indicator strains, 81.11 per cent of the strains were typable into ten perfringocin types. Type "a" and "b" alone could type 47.92 per cent of the strains. Type "f" was predominantly found to be for the American strains and "b" and "c" for the Indian strains. Active perfringocin typing developed for the first time for the food poisoning strains of C. perfringens type A was expected to prove useful in the epidemiological investigations. PMID- 6265388 TI - Inhibition by x-rays of isoproterenol-induced increase in cAMP content in parotid gland is not due to direct action on the plasma membranes. PMID- 6265391 TI - The airway mucociliary system. PMID- 6265392 TI - [A 29-year-old patient with fever, leukopenia, anemia and hepatosplenomegaly]. PMID- 6265393 TI - [Syncope attacks with vertigo and sweating]. PMID- 6265394 TI - [Progressive reversible kidney insufficiency after blood pressure reduction with captopril]. PMID- 6265395 TI - Electron-opaque inclusions in the rat retinal pigment epithelium after treatment with chelators of zinc. AB - Sprague-Dawley male rats given intraperitoneal injections of zinc chelators, namely dithizone and 1,10-phenanthroline, had unusual osmiophilic inclusion bodies in their retinal pigment epithelium (RPE). These structures were not seen in untreated or vehicle-treated controls. The morphology of the inclusion bodies clearly distinguished them from cytoplasmic organelles observed normally in the RPE. The number of inclusion bodies is dose-dependent. The bodies do not have the morphological characteristics of lipid droplets seen infrequently in the untreated rat RPE. The results suggest that sequestration of zinc, either rapidly with injections of dithizone or more slowly with daily administration of 1,10 phenanthroline, exerts pronounced effects on the retinal pigment epithelial cells. PMID- 6265396 TI - Proposed antigenic classification of registered arboviruses I. Togaviridae, Alphavirus. PMID- 6265398 TI - Influence of cells and virus multiplicity on the inhibition of herpesviruses with acycloguanosine. AB - The inhibition of herpes simplex virus type 1 (HSV-1) plaque formation by acycloguanosine (ACG) was assayed in human fetal lung fibroblasts (HL), cell lines from human cervical carcinoma, rabbit cornea, and human rhabdomyosarcoma, and three green monkey kidney cell lines. The ACG concentration giving 50% plaque reduction (PR50) of HSV-1 was lowest in HL. In two green monkey kidney cell lines, HSV-1 plaque formation was relatively insensitive to ACG, with PR50 of 25 and 60 muM, respectively. In the other cells, HSV-1 showed an intermediate sensitivity to ACG. Also, HSV-2 was more sensitive to ACG in HL than in monkey kidney cells. HSV-1 plaque reduction on HL cells was studied as a function of increasing virus MOI with a constant concentration of ACG. An increased MOI decreased the sensitivity to ACG. The sensitivity of cytomegalovirus (CMV), strain Ad. 169, and four fresh CMV isolates to ACG was studied in HL cells. At low MOIs, three of the five CMV strains were somewhat sensitive to ACG, PR50 values ranging from 60 to 450 muM ACG. At high MOIs none of the virus strains were sensitive. ACG at concentrations of 200 muM or less did not significantly affect host cell DNA synthesis, as measured by 3H-thymidine incorporation. In cell culture, the inhibition of herpesviruses by ACG appears to be complex, depending on the type of virus, virus concentration, type of host cells, and condition of the cells. PMID- 6265397 TI - Inhibition of the replication of human cytomegalovirus by bromodeoxycytidine in the absence of detectable increases in bromodeoxycytidine kinase activity. PMID- 6265399 TI - Immunoelectron microscopic localization of Rous sarcoma virus structural protein p27 in infected chicken embryo fibroblasts. AB - The immunoperoxidase technique was employed to localize, at the ultrastructural level, protein Pr76 (a precursor of the 'gag' gene protein of avian leukemia and sarcoma viruses) in chick embryo cells infected with RSV-RAV-2 virus. The protein was confined to free and membrane-bound ribosomes. This was often particularly conspicuous in the perinuclear region. No staining was found in the ergastoplasmic cisternae, in the Golgi apparatus, or in the nucleus. This pattern of localization is compatible with previous studies where the protein was searched for in various cell subfractions. PMID- 6265401 TI - Quantitation of cell DNA in the evaluation of heteroploid cells as substrate for the preparation of killed viral vaccines. AB - To evaluate the risk of using heteroploid cell lines as substrates for viral vaccine production, the presence of cell DNA in poliovirus suspensions was examined. The time course of [3H]-thymidine-labeled HeLa cell DNA release during lytic infection with type 1 poliovirus was investigated. More DNA was found in filtered supernatants of poliovirus-inoculated cultures than in control cell supernatants. DNA concentration increased with time, paralleling virus release, but did not exceed 1.5% of the total DNA content of the culture. Only about 10% of this cell DNA was resistant to DNase treatment. By both ion-exchange chromatography and rate-zonal centrifugation it was possible to remove practically all cell DNA contaminating filtered poliovirus suspensions. Results obtained in this study permitted quantitative evaluation of cell substrate DNA present in poliovirus suspensions during successive steps of killed poliovirus vaccine preparation. Based on the sensitivity of our method, the amount of residual DNA was estimated at less than 0.02 pg per dose of purified vaccine. PMID- 6265400 TI - Natural antibodies to EBV-VCA antigens in common marmosets (Callithrix jacchus) and response after EBV inoculation. AB - Healthy common marmosets from two separate colonies, one in England and one in France, were found to have antibodies cross-reacting with Epstein-Barr virus structural antigens (EBV-VCA). All seropositive animals were at least 2 years old. Experimental EBV infection of marmosets of different ages led to seroconversion of inoculated weanlings. Adult animals either developed antibody for the first time or showed an increase in their existing titers. Both control and infected animals developed a progressive interstitial nephritis. The lymphocytic infiltration was more extensive, diffuse and immature in appearance in inoculated animals, but no definite evidence of lymphoproliferative disease or lymphoma was found. PMID- 6265402 TI - Inhibitory effects of an aromatic retinoid (Ro 10-9359) on viral tumorigenesis. AB - Prophylactic treatment of hamsters and chickens with an aromatic retinoid (Ro 10 9359) inhibited Rous sarcoma virus (RSV) tumorigenesis. Retinoid administration to chickens with RSV-induced tumors resulted in tumor regression and/or confinement to the primary site. The retinoid also exerted a therapeutic effect on Shope virus papilloma development in the skin of rabbits. PMID- 6265403 TI - Transformation-defective virus generation from cloned nondefective avian sarcoma virus. PMID- 6265404 TI - Effect of denervation on cyclic amp regulating enzymes in the rat gastrocnemius muscle. AB - The activities of cyclic AMP regulatory enzymes (adenylate cyclase and phosphodiesterase) were studied in rat gastrocnemius muscle after denervation. Basal adenylate cyclase activity in whole homogenate increased progressively from the 3rd day reaching values more than 7-fold those of the controls 30 days after denervation. No significant differences between the contralateral and denervated muscle were detected as regards adenylate cyclase activation by catecholamines or NaF. Carbamylcholine was with effect. Cyclic AMP phosphodiesterase activity increased significantly at 3 days after denervation as was still significantly elevated at 60 days. PMID- 6265405 TI - Characterization of NAD-glycohydrolase in rat lymphoid organs. AB - Rat thymus and thymocytes possess an NAD-glycohydrolase activity lower than spleen and spleen lymphocytes. In all cases, the highest activity (50%) is bound to the nuclei, while that in the soluble fraction is higher (in percent) in the lymphocytes than in the whole organ. Considering that thymus and thymocytes are characterized by a soluble NAD-ase activity higher than in spleen and in spleen lymphocytes, and that lymphocytes in general have a greater soluble than microsomal activity, we interpret these findings are evidence that the soluble NAD-ase is due essentially to T lymphocytes, of which it represents a typical feature. PMID- 6265406 TI - Increased responsiveness to adenosine 3'5'-cyclic monophosphate-active agents during the immune response in vivo. AB - Cytotoxic T lymphocytes (CTL) were generated in the spleen following immunization of C57BL/6 mice with allogeneic cells. The activity of such CTL was inhibited by agents that increased intracellular adenosine 3'5',-cyclic monophosphate (cAMP) levels. During the primary immune response, the susceptibility of CTL to inhibition by theophylline remained constant, but susceptibility to histamine, prostaglandin E2 (PGE2). dibutyryl cAMP, and 4-(3-butoxy-4-methoxybenzyl)-2 imidazolidinone (Ro-20-1724) increased significantly. The pattern of increased inhibition by histamine differed from that of the other agents. Increased cAMP responsiveness of CTL resulted from at least two distinct biochemical events, possibly including 1) increased receptors and/or increased receptor-adenylate cyclase coupling (for histamine); and 2) increased efficiency of a post cAMP pathway (for dibutyryl cAMP, PGE2, and Ro 20-1724). PMID- 6265407 TI - Evaluation of free radical scavengers in studies of lymphocyte-mediated cytolysis. AB - Oxygen centered radicals derived from potassium superoxide (KO2) in solution were found to be toxic to P815 mastocytoma target cells. Protection of P815 cells from chemically generated radicals was mediated most efficiently by Tiron, a low molecular weight scavenger of superoxide radicals (O2-). Superoxide dismutase (SOD) and catalase also afforded protection. In vivo cytolysis of P815 target cells mediated by allogeneic lymphocytes sensitized in vivo to tumor cells was inhibited by reducing the amount of oxygen available for metabolism and by radical scavengers. Ferricytochrome c, Tiron, and phenol, all of which are relatively low molecular weight radical scavengers, inhibited cytolysis in a dose dependent manner, while mannitol, a hydroxyl radical scavenger, did not. High molecular weight scavengers like SOD and catalase had no effect. The inhibition of cytolysis by radical scavengers was found to be independent of toxic effects on effector cells, chelation of ions, or indirect effects on prostaglandin biosynthesis. Pretreatment of either effector or target cells with Tiron had no effect on LMC. The data suggest a possible role for free radicals in molecular events leading to target cell injury by sensitized lymphocytes. PMID- 6265408 TI - Proton-recoil neutron dosimeter for personnel monitoring. PMID- 6265409 TI - Non-Hodgkin's lymphoma of the nose and paranasal sinuses: a study of 17 cases. AB - Non-Hodgkin's lymphoma of the nose and paranasal sinuses occurred in 14 men and 3 women with a mean age of 61 years. Nasal obstruction, unilateral facial swelling, and nasal discharge were frequent initial manifestations. The maxillary sinus and nose were the commonest primary sites. Using Rappaport's classification, there were 9 histiocytic, 5 poorly differentiated lymphocytic, and 3 mixed histiocytic lymphocytic lymphomas. Sixteen patients had radiation therapy to the primary site, and 9 patients later received chemotherapy. Eleven patients (69%) are dead, with a median survival time of 11 months after diagnosis. Dissemination of lymphoma was the most common cause of death. Five patients (29%) are alive up to 40 months after diagnosis. Patients with poorly differentiated lymphocytic lymphoma survived longer than those with histiocytic or mixed histiocytic lymphocytic lymphomas (medium survival times 35, 9, and 12 months, respectively). Poor response to radiation therapy and dissemination of lymphoma were poor prognostic indicators. PMID- 6265410 TI - Practical applications of the microphotometric quantification of histoenzyme reactions. AB - There are many histochemical reactions which can be used for the accurate topographic detection of enzymes in tissues. There are also many reports of applications of these techniques in which the results have been evaluated subjectively. However, only a few of these methods have been the subject of quantification, using different methodologies, most of them based on microphotometry. A critical analysis of these procedures has generally shown that they are valid either relatively or at an absolute level. Nevertheless, the routine application of these methods is not as widespread as one might expect. In this paper, the methodological developments that have taken place in the histochemical assay of some enzymes by microspectrophotometry are reviewed briefly. The enzymes include acid phosphatase, non-specific esterase, succinate dehydrogenase and cytochrome oxidase. These methods have given consistent and useful results when applied to our experimental models of irradiated skin, and thus seem useful for various other applications. The reasons why there have been so few applications for quantitative histochemistry are also discussed together with possible ways of making its use more general. PMID- 6265412 TI - Further studies on a unique T-tubular acid phosphatase in avian skeletal muscle. AB - With the unique observation, using conventional cytochemistry, of acid phosphatase reaction production in the T-tubules of the posterior latissimus dorsi muscle of the chicken, the possibility of endocytosis of lysosomal enzymes by muscle cells came into question. After testing the substrate specificity of this T-tubular phosphatase, it was clear that the enzyme hydrolysed glucose 6 phosphate and beta-glycerophosphate at pH 5.0 but not cytidine-5'-monophosphate which was hydrolysed by dense bodies and autophagic vacuoles. The cytochemical evidence points to a unique phosphatase present on muscle cell membranes which apparently does not belong to the vacuolar apparatus of skeletal muscle and is not 5'-nucleotidase. PMID- 6265413 TI - Treatment of small cell carcinoma of lung with combined high dose mediastinal irradiation, whole brain prophylaxis and chemotherapy. PMID- 6265415 TI - Community nursing--a psychosocial learning experience. PMID- 6265414 TI - Effect of saline loading during heat acclimatization on adrenocortical hormone levels. AB - Six male subjects were acclimatized to heat; once they were given sufficient 1% saline to prevent the occurrence of a salt deficit during acclimatization, and another time they were given no saline. Plasma aldosterone (PA), plasma cortisol (PC), plasma renin activity (PRA), and plasma electrolytes were measured before, during, and after and sweat electrolytes before and after the 11-day acclimatization program. PRA and PA were significantly increased by the acute stress of heat and exercise but were unaffected by acclimatization. These increases were attenuated, but not prevented, by drinking saline, whereas sweat [Na] and PC were reduced by acclimatization but were unaffected by saline. Thus adrenocortical activity has been shown not to be increased after heat acclimatization, and mineralocorticoid activity, although potentiated by a Na deficit, appears to be determined primarily by the acute stress of heat and of exercise. Hence, the increased Na conservation with acclimatization is likely to be a normal response to heat and exercise even in the absence of a negative Na balance. PMID- 6265416 TI - The historical development of American nursing education. PMID- 6265411 TI - Microscopical methods for the localization of Na+,K+-ATPase. AB - Na+,K+-ATPase plays a central role in the ionic and osmotic homeostasis of cells and in the movements of electrolytes and water across epithelial boundaries. Microscopic localization of the enzyme is, therefore, of crucial importance in establishing the subcellular routes of electrolyte flow across structurally complex and functionally polarized epithelia. Recently developed approaches to the localization of Na+,K+-ATPase are reviewed. These methods rely on different properties of the enzyme and encompass cytochemical localization of the K+ dependent nitrophenylphosphatase component of the enzyme, autoradiographic localization of tritiated ouabain binding sites, and immunocytochemical localization of the holoenzyme and of its catalytic subunit. The rationales for each of these techniques are outlined as are the criteria that have been established to validate each method. The observed localization of NA+,K+-ATPase in various tissues is discussed, particularly as it relative to putative and hypothetical mechanisms that are currently thought to mediate reabsorptive and secretory electrolyte transport. PMID- 6265417 TI - Community health education for senior citizens. PMID- 6265418 TI - Prospects for change: some evaluative reflections from one articulated Baccalaureate program. PMID- 6265419 TI - Teaching nursing ethics: a practical approach. PMID- 6265420 TI - Progeny testing for bovine syndactyly. PMID- 6265421 TI - Estimation of penicillin concentrations and penicillin metabolising enzyme activities by the Lowry reaction. PMID- 6265422 TI - An electron spin resonance study of a spin adduct of the non-protein component (NPC) of neocarzinostatin. PMID- 6265423 TI - Baird-Parker medium supplemented with acriflavine, polymyxins and sulphonamide for the selective isolation of Staphylococcus aureus from heavily contaminated materials. PMID- 6265424 TI - In-vitro activity of the novel oxa-beta-lactam antibiotic moxalactam (LY 127935) against dense populations of selected Gram-negative bacilli. AB - The activity of moxalactam, a new beta-lactam antibiotic with a novel molecular structure, was examined against dense populations of a variety of Gram-negative bacilli. The lytic activity of moxalactam against ampicillin-sensitive strains was similar to ampicillin, but the activity was maintained against ampicillin resistant strains, including Pseudomonas aeruginosa, irrespective of whether the ampicillin resistance was 'intrinsic' (non-enzymic) or due to beta-lactamase. Of the 18 strains tested only one, a Hafnia sp., failed to respond to moxalactam. PMID- 6265425 TI - Cefotaxime--a clinical study. PMID- 6265426 TI - N-Formimidoyl thienamycin (MK0787): in-vitro antibacterial activity and susceptibility to beta-lactamases compared with that of cefotaxime, moxalactam and other beta-lactam antibiotics. PMID- 6265427 TI - Comparative in-vitro activity of moxalactam and cefotaxime against isolates from blood culture. PMID- 6265428 TI - The combination of pivmecillinam and pivampicillin in the treatment of acute enteric fever. PMID- 6265429 TI - Pharmacokinetics of cefoperazone, moxalactam, cefotaxime, trimethoprim and sulphamethoxazole in experimental meningitis. PMID- 6265430 TI - The in vitro activity of acyclovir and related compounds against cytomegalovirus infections. PMID- 6265432 TI - An adenosine triphosphate-dependent deoxyribonuclease from Bacillus laterosporus. Improved purification, subunit structure and substrate specificity. AB - The ATP-dependent deoxyribonuclease from Bacillus laterosporus has been purified to near homogeneity by a procedure involving ammonium sulfate fractionation, DEAE cellulose chromatography, Sephadex G-150 gel filtration, DEAE-Sephadex A-25 chromatography and DNA-cellulose affinity chromatography. The purified enzyme has a molecular weight of 210,000 +/- 8,000 as determined by sucrose gradient sedimentation. It is composed of two nonidentical polypeptide chains with close molecular weights of around 110,000. The substrate preference of the pure enzyme is essentially identical with the previous result obtained with the partially purified enzyme preparation (Anai, M., Mihara, T., Yamanaka, M., Shibata, T., & Takagi, Y. (1975) J. Biochem. 78, 105-114). Thus, the enzyme degrades double stranded DNA about 100 times faster than heat-denatured DNA in the presence of ATP. Double-stranded DNA is not degraded to any measurable extent in the absence of ATP, but the enzyme exhibits activity toward denatured DNA in the absence of ATP. Furthermore, no endonuclease activity is observed on covalently closed circular duplex DNA and open circular duplex DNA. PMID- 6265433 TI - Inhibitory effect of pyridoxal 5'-phosphate on the DNA binding site of ATP dependent deoxyribonuclease from Bacillus laterosporus. AB - Bacillus laterosporus ATP-dependent deoxyribonuclease has been found to be inhibited by pyridoxal 5'-phosphate. The inhibition is specific for pyridoxal 5' phosphate and pyridoxal which are required in relatively high concentrations. Pyridoxamine 5'-phosphate, pyridoxamine, and pyridoxine are ineffective. The inhibition is reversed by dilution or dialysis but can be changed to an irreversible inactivation by reduction of the enzyme . pyridoxal 5'-phosphate complex with sodium borohydride. The compound is a competitive inhibitor with respect to DNA but not ATP. Moreover, the presence of DNA substrate protects the enzyme against this inactivation but the presence of ATP shows no effect. The reduced enzyme . pyridoxal 5'-phosphate complex displays a new absorption maximum at 325 nm and a fluorescence emission at 390-400 nm when excited at 325 nm which are characteristic for epsilon-N-(phosphopyridoxyl)lysine. Thus, B. laterosporus DNase appears to have an essential lysine residue at the DNA binding site of the enzyme, and the enzyme possess two different active sites, a DNA binding site and an ATP binding site. PMID- 6265431 TI - Purification and characterization of bovine dental sac collagenase. AB - 1. Active type collagenase was purified as much as 140-fold from the explant medium of bovine dental sacs and showed a single band on disc gel electrophoresis. Purified collagenase cleaved native collagen at only one locus under physiological conditions, but hydrolyzed neither gelatin nor alpha-casein. The optimal pH was about 7.8. 2. The molecular weight of active type enzyme was 35,000 by gel filtration and 34,000 by gel electrophoresis. The activation of latent type of collagenase resulted in the reduction of molecular weight from 45,000 to 38,000 by gel filtration. 3. A small but detectable amount of collagenase was directly extracted from frozen and thawed bovine dental sacs. In explant media of frozen and thawed tissue and fresh tissue with actinomycin D, some activity was detected for the first 2 days, but essentially no collagenase activity was detected in the explant medium after day 3. 4. The latent type collagenase was activated by trypsin, 4-aminophenylmercuric acetate (4-APMA), thiocyanate and deoxycholate (DOC). DOC showed irreversible dissociation of latent type enzyme in similar fashion to that exerted by 4-APMA. 5. The purified collagenase was inhibited by bovine serum, EDTA, o-phenanthroline, cysteine and dithiothreitol. PMID- 6265434 TI - A role of H+ flux in active Ca2+ transport into sarcoplasmic reticulum vesicles. I. Effect of an artificially imposed H+ gradient on Ca2+ uptake. AB - To ascertain the function of H+ flux in active Ca2+ transport into sarcoplasmic reticulum vesicles, the effect of pH gradient on Ca2+ transport was examined. A transient H+ gradient (inside-acidic) was imposed on K+-loaded sarcoplasmic reticulum vesicles with the aid of K+-H+ exchange driven by nigericin. This proton gradient was dissipated rapidly and concomitantly with ATP-driven Ca2+ transport. Under these conditions, the initial rate of the Ca2+ uptake was increased about 1.5-fold. The stimulation of Ca2+ uptake was completely lost when the pH gradient was cancelled with an uncoupler plus membrane permeable cation before Ca2+ uptake. These results are interpreted in terms of H+ efflux coupled with Ca2+ transport. PMID- 6265435 TI - A role of H+ flux in active Ca2+ transport into sarcoplasmic reticulum vesicles. II. H+ ejection during Ca2+ uptake. AB - Proton efflux during Ca2+ transport into sarcoplasmic reticulum vesicles was examined. Although a rapid H+ ejection was observed during the initial phase of Ca2+ uptake and the amount of the liberated H+ was more than that due to hydrolysis of ATP, generation of a pH difference as a result of the H+ efflux could not be detected by direct pH measurement with a pH meter. Alkalinization of the inside of the vesicles during Ca2+ uptake was more precisely examined by flow dialysis assay and a significant uptake of acetate or salicylate into the vesicles was found, suggesting the generation of a small pH difference across the SR membrane. From these results, it was concluded that counter-transport of H+ was operative in Ca2+ uptake but that only a relatively small pH difference was generated as a result of the H+ efflux. The intrinsic buffering capacity of sarcoplasmic reticulum vesicles was measured and a relatively large value (130 nmol H+/pH unit/mg at pH 6.2) was obtained. PMID- 6265436 TI - Adenosine 3',5'-monophosphate-receptor protein and protein kinase in Coprinus macrorhizus. AB - A single cAMP-receptor protein could be detected in mycelial extracts of Coprinun macrorhizus by using the photoaffinity cAMP-analogue, 8-N3-cAMP. The protein which specifically bound 32P-labeled 8-N3-cAMP had an apparent molecular weight of 46,000 as determined by an SDS-polyacrylamide gel electrophoresis system. The 46,000-dalton protein was characterized by the dissociation constant for [32P]-8 N3-cAMP, and by the nucleotide specific inhibition of [32P]-8-N3-cAMP binding. The 46,000-dalton protein was co-chromatographed on a DEAE-cellulose column with cAMP-dependent protein kinase. The levels of [32P]-8-N3-cAMP-binding and protein kinase activities in mycelial extracts of strains used was always in parallel. The result indicated that the 46,000-dalton protein may be a regulatory subunit of protein kinase with the capacity to bind cAMP. cAMP-dependent protein kinase of this fungus was immunologically different from those of higher animals. PMID- 6265437 TI - Potential mechanism of insulin action on glucose transport in the isolated rat diaphragm. Apparent translocation of intracellular transport units to the plasma membrane. AB - [3H]Cytochalasin B binding and its competitive inhibition by D-glucose have been used to quantitate the number of functional glucose transport units in plasma and microsomal membranes prepared from intact rat diaphragm. In a series of three experiments, plasma membranes prepared from diaphragms which have not been incubated with insulin bind approximately 16 pmol of cytochalasin B/mg of membrane protein to the D-glucose-inhibitable binding site. If 280 nM (40,000 microunits/ml) insulin is present during the incubation, cytochalasin B binding to the plasma membranes is increased approximately 2-fold without alteration in the dissociation constant of this site. Membranes in the microsomal fraction prepared from diaphragms which have been incubated for 30 min in the absence of insulin contain 21 pmol of D-glucose-inhibitable cytochalasin B binding sites/mg of membrane protein. However, in the presence of insulin during the incubation period, the number of these sites in the microsomal fraction is decreased to 12 pmol/mg of membrane protein. These results suggest that insulin stimulates glucose transport in the isolated rat diaphragm primarily through a translocation of functional glucose transport units from an intracellular membrane pool to the plasma membrane. These results are similar to the results observed in rat adipose cells (Cushman, S. W., and Wardzala, L. J. (1980) J. Biol. Chem. 255, 4758-4762) and suggest that this mechanism of insulin-stimulated glucose transport activity may be general to other cell types. PMID- 6265438 TI - Hydrogen peroxide kills Staphylococcus aureus by reacting with staphylococcal iron to form hydroxyl radical. AB - Two lines of investigation supported the premise that killing of Staphylococcus aureus, 502A, by hydrogen peroxide involves formation of the more toxic hydroxyl radical (.OH) through the iron-dependent Fenton reaction. First, growing S. aureus overnight in broth media with increasing concentrations of iron increased their content of iron and dramatically enhanced their subsequent susceptibility to killing by H2O2. Second, in direct relation to their effectiveness as .OH scavengers, thiourea, dimethyl thiourea, sodium benzoate, and dimethyl sulfoxide inhibited H2O2-mediated killing of S. aureus. PMID- 6265439 TI - Molecular properties of the enzymic phytohemagglutinin of mung bean. AB - Mung bean seeds possess a tetrameric galactose-binding protein that displays two types of activities: (a) a hemagglutinin activity, and (b) an alpha-galactosidase activity. This protein can be reversibly converted by pH changes from a tetrameric form, which possesses both enzymic and hemagglutinin activities, to a monomeric form which possesses enzymic activity only. This observation suggests that the enzymic phytohemagglutinin is an aggregated form of a monomeric alpha galactosidase. The tetrameric alpha-galactosidase has a pH optimum of about pH 7.0, while the monomeric form displays a pH optimum of 5.6. Circular dichroism difference spectra and inhibition studies suggest that aggregation induces conformational changes in the subunits sufficient to alter their enzymatic properties. The possibility of in vivo changes in subunit equilibria, when combined with the accompanying alterations in activity, provides a new concept worthy of consideration with respect to the physiological role of phytohemagglutinins. PMID- 6265441 TI - Cytochrome c as an electron shuttle between the outer and inner mitochondrial membranes. AB - Addition of exogenous NADH to rotenone- and antimycin A-treated mitochondria, in 125 mM KCl, results in rates of oxygen uptake of 0.5-1 and 10-12 nanoatoms of oxygen X mg protein-1 X min-1 in the absence and presence of cytochrome c, respectively. During oxidation of exogenous NADH there is a fast and complete reduction of cytochrome b5 while endogenous or added exogenous cytochrome c become 10-15% and 100% reduced, respectively. The reoxidation of cytochrome b5, after exhaustion of NADH, precedes that of cytochrome c. NADH oxidation is blocked by mersalyl, an inhibitor of NADH-cytochrome b5 reductase. These observations support the view of an electron transfer from the outer to the inner membrane of intact mitochondria. Both the rate of exogenous NADH oxidation and the steady state level of cytochrome c reduction increase with the increase of ionic strength, while the rate of succinate oxidation undergoes a parallel depression. These observations suggest that the functions of cytochrome c as an electron carrier in the inner membrane and as an electron shuttle in the intermembrane space are alternative. It is concluded that aerobic oxidation of exogenous NADH involves the following pathway: NADH leads to NADH-cytochrome b5 reductase leads to cytochrome b5 leads to intermembrane cytochrome c leads to cytochrome oxidase leads to oxygen. It is suggested that the communication between the outer and inner membranes mediated by cytochrome c may affect the oxidation-reduction level of cytosolic NADH and the related oxidation-reduction reactions. PMID- 6265440 TI - Hydrogen peroxide causes the fatal injury to human fibroblasts exposed to oxygen radicals. AB - Oxygen radicals are suspected as being a cause of the cellular damage that occurs at sites of inflammation. The phagocytic cells that accumulate in areas of inflammation produce superoxide, hydrogen peroxide, hydroxyl radical, and probably singlet oxygen in the extracellular fluid. The mechanism by which these oxygen molecules kill cells is unknown. To determine which of the oxygen species is responsible for the cellular killing, we exposed human fibroblasts in culture to oxygen radicals generated by the enzymatic action of xanthine oxidase upon acetaldehyde. Using the amount of chromium-51 released from labeled fibroblasts as an index of cellular death, we found that cells were protected only by interventions that reduce hydrogen peroxide concentration. Agents that inactivate superoxide, hydroxyl radical, and singlet oxygen were ineffective in limiting oxygen radical-induced cellular death. PMID- 6265442 TI - Studies on the phosphorylation of muscle phosphofructokinase. AB - Phosphorylation of rabbit skeletal muscle phosphofructokinase by the catalytic subunit of cyclic AMP-dependent protein kinase occurs with a Km of about 230 microM and Vmax approaching that seen with histone as a substrate. The rate of phosphorylation of phosphofructokinase by protein kinase is increased by allosteric activators of phosphofructokinase, whereas inhibitors of phosphofructokinase inhibit the phosphorylation. Inhibitors and activators change Vmax but not Km. The site of phosphorylation is a serine residue that is the sixth amino acid from the carboxyl terminus. Limited proteolysis by trypsin releases an octapeptide from the carboxyl terminus and a brief exposure to subtilisin releases a dodecapeptide from the carboxyl end. The sequence of the dodecapeptide is His-Ile-Ser-Arg-Lys-Arg-Ser(P)-Gly-Glu-Ala-Thr-Val. Phosphofructokinase isolated from a rabbit injected 18 h prior to killing with [32P]PO4 contained covalently bound radioactive phosphate. Approximately 80% of the phosphate was released in a trichloroacetic acid-soluble form following limited proteolysis by trypsin, under which conditions the enzyme remained with a monomer size of about 80,000 daltons. The position of elution from Sephadex G-25 of the phosphopeptide was identical with that found following limited trypsin proteolysis of in vitro labeled enzyme. Migration of the phosphopeptides on thin layer cellulose chromatography was also identical. We conclude that at least 80% of the radioactive phosphate introduced within 18 h of an intravenous injection of [32P]PO4 is found at the same site as that introduced by phosphorylation with the catalytic subunit of cyclic AMP-dependent protein kinase. PMID- 6265443 TI - Structure of the metal-nucleotide complex in the acetate kinase reaction. A study with gamma-32P-labeled phosphorothioate analogs of ATP. AB - The synthesis of the gamma-32P-labeled diastereomers of adenosine 5'-O-(1 thiotriphosphate) (ATP alpha S) and the Sp isomer of adenosine 5'-O-(2 thiotriphosphate) (ATP beta S) by a modification of the Glynn and Chappell method (Glynn, I. M., and Chappell, J. T., (1964) Biochem. J. 90, 147-149) is described. These analogs were tested as substrates for acetate kinase in the presence of several divalent metal ions. Both isomers of ATP alpha S are substrates in the presence of Mg2+, Mn2+, Co2+, Zn2+, and Cd2+, the Sp isomer being preferred by a factor of between 4.8 (Mg2+) and 52.5 (Cd2+). Only the Rp isomer of ATP beta S is a substrate in the presence of Mg2+, and the Sp isomer becomes a better substrate in the presence of Mn2+, Co2+, and Zn2+; both isomers are equally good substrates in the presence of Cd2+. The change in specificity upon replacing Mg2+ by Cd2+ is greater than 1800 at beta-phosphorus and 10 at alpha phosphorus. These results provide a basis for proposing that the lambda screw sense configuration of the beta, gamma-bidentate MgATP complex is the substrate for acetate kinase. In the reverse reaction, both Sp and Rp isomers of ADP alpha S are substrates in the presence of all metal ions tested, the Sp isomer preferred by a factor between 12.3 (Mg2+) and 45.5 (Cd2+). In the presence of Mg2+, Mn2+, and Co2+, only the Rp isomer of ATP beta S is synthesized from prochiral ADP beta S, while a mixture of Rp and Sp isomers is synthesized in the presence of Zn2+ and Cd2+. These results are analogous to those for the forward reaction and suggest that the Mg.ADP complex which binds as a substrate in the reverse reaction, and is released as a product in the forward reaction, is the beta-monodentate. The classification of acetate kinase as an enzyme having a type I mechanism (Dunaway-Mariano, D. and Cleland, W. W. (1980) Biochemistry 19, 1506-1515) for kinases, is discussed. PMID- 6265444 TI - Appearance of the intestinal cytosolic receptor for 1,25-dihydroxyvitamin D3 during neonatal development in the rat. AB - During the early suckling period in the rat, active calcium uptake by the intestine is refractory to stimulation by 1,25-dihydroxyvitamin D3. To determine the role that the specific cytosolic receptor for 1,25-dihydroxyvitamin D3 plays in this refractory state, the concentration of the receptor and its binding characteristics were measured during the neonatal period. From Scatchard analysis, the concentration of receptor in the adult intestine was 563 +/- 64 fmol/mg of protein. At 28 and 21 days postpartum, receptor concentrations were 711 +/- 129 and 251 +/- 36 fmol/mg of protein, respectively. Estimates from sucrose density gradient profiles and Scatchard analyses indicated that, at 14 and 7 days postpartum, receptor concentrations were less than 50 fmol/mg of protein. Equilibrium dissociation constants were similar at all times measured and ranged from 0.38 to 0.52 nM. These results suggest that the lack of response observed in the early neonatal intestine to 1,25-dihydroxyvitamin D3 may stem, at least in part, from the relative absence of receptors for 1,25-dihydroxyvitamin D3. Furthermore, the appearance of the receptor may be the determining factor in the initiation of active calcium absorption in the intestine and its regulation. PMID- 6265445 TI - Serum catecholamines desensitize beta-adrenergic receptors of cultured C6 glioma cells. AB - C6 glioma cells grown in medium containing fetal bovine serum have a decreased beta-adrenergic receptor number and beta-receptor-stimulated cyclic AMP accumulation as compared to cells grown in a serum-free, defined medium. The decreased number of receptors and decreased cAMP accumulation are attributable to a suppression of receptor binding and response by serum as opposed to increases produced by growth in the defined medium. Serum, when added to cells grown in the absence of serum, stimulated cellular cyclic AMP levels to 2-3 times basal levels. This direct stimulatory effect was blocked by incubation of the cells with the beta-adrenergic antagonist propranolol and was partially reversed by dialysis of the serum. In contrast, addition of serum to cells that have been grown with serum fails to stimulate cyclic AMP accumulation. The decrease in receptors following growth in serum can be mimicked by growing cells in serum free medium in the presence of beta-adrenergic agonists such as isoproterenol or norepinephrine. Radioenzymatic assays indicate that fetal bovine serum contains approximately 0.3 nM norepinephrine and lower concentrations of epinephrine. It thus appears that growth of C6 cells in serum-containing media desensitizes the beta-adrenergic receptor/cyclic AMP system of these cells. This desensitized state appears to result primarily from the action of catecholamines present in serum. These data indicate that retained catecholamines are one component in serum that can modify expression of beta-adrenergic receptors and hormonal response of cultured glioma cells. PMID- 6265446 TI - Oxidation reactions by prostaglandin cyclooxygenase-hydroperoxidase. AB - oxidations of organic sulfides, amines, and even enzymes catalyzed by purified and microsomal forms of prostaglandin cyclooxygenase-hydroperoxidase have been studied using O2 incorporation into arachidonic acid to monitor oxygenase and [14C]15-hydroperoxyprostaglandin E2 reduction to prostaglandin E2 to measure hydroperoxidase. The oxygenase was protected by phenol against the irreversible deactivation induced by low levels of hydroperoxides. Furthermore, the EPR signal noted during reactions with the microsomal enzyme probably reflected the adventitious oxidation of endogenous materials. As described previously for phenol and other reducing cosubstrates, methyl phenyl sulfide (MPS) increased hydroperoxidase activity at all concentrations studied, while stimulating oxygenase at low levels and inhibiting it at 5-10 mM. In stoichiometric equivalence with 15-hydroperoxyprostaglandin E2 reduction, MPS was enzymatically oxidized to its analogous sulfoxide, methylphenyl sulfoxide, acquiring an oxygen atom exclusively from the hydroperoxide and demonstrating some chiral character. In contrast, other oxidizable compounds such as N,N-dimethylphenylenediamine and aminopyrine reacted via radical intermediates. Phenylbutazone, which is oxidized using dissolved molecular oxygen, did not compete with MPS oxidation. Hence, MPS was oxidized while bound to the enzyme, whereas the amine oxidation occurred in solution via an enzyme-formed oxidant. The Soret peak noted with cyclooxygenase hydroperoxidase was examined as a possible measure of this binding, but was also noted in denatured and deactivated enzyme, suggesting that its relevance should be reconsidered. Despite the similarities in their drug-metabolizing profiles, cyclooxygenase-hydroperoxidase is clearly distinct from cytochrome P-450. The mechanism of this hydroperoxidase is considered in the context of other more extensively studied peroxidases. PMID- 6265447 TI - Thermolabile CDP-choline synthetase in an animal cell mutant defective in lecithin formation. PMID- 6265448 TI - Definition of cytochrome c binding domains by chemical modification. Interaction of horse cytochrome c with beef sulfite oxidase and analysis of steady state kinetics. PMID- 6265449 TI - Subcellular fractionation studies on the post-translational processing of pro adrenocorticotropic hormone/endorphin in rat intermediate pituitary. AB - The subcellular localization of the post-translational processing steps which occur in the conversion of pro-adrenocorticotropic hormone (ACTH)/endorphin into beta-endorphin-sized molecules in rat intermediate pituitary has been studied. Primary cell cultures were incubated in radioactively labeled amino acids, and a subcellular fraction containing secretory granules was separated from a subcellular fraction containing rough endoplasmic reticulum and Golgi apparatus by centrifugation of homogenates on gradients on Percoll (Pharmacia Fine Chemicals). The radiolabeled beta-endorphin-related material in the granule and rough endoplasmic reticulum/Golgi apparatus fractions was quantitated by immunoprecipitation and sodium dodecyl sulfate polyacrylamide gel electrophoresis. A pulse-chase labeling experiment demonstrated that newly synthesized beta-endorphin-related material first appeared in the rough endoplasmic reticulum/Golgi apparatus fraction and after longer incubations (chase) appeared in the secretory granule fraction. After 2 h of chase incubation, about 85% of the beta-endorphin-related material synthesized during the 30-min pulse incubation had been transferred from the rough endoplasmic reticulum/Golgi apparatus to the secretory granule fraction. The conversion of most of the newly synthesized pro-ACTH/endorphin into beta-lipotropin occurred in the rough endoplasmic reticulum/Golgi apparatus fraction, whereas the conversion of most of the beta-lipotropin into beta-endorphin-sized molecules occurred in the secretory granule fraction. PMID- 6265450 TI - Insulin and glucagon stimulation of (Na+-K+)-ATPase transport activity in isolated rat hepatocytes. AB - The effects of insulin and glucagon on the (Na+-K+)-ATPase transport activity in freshly isolated rat hepatocytes were investigated by measuring the ouabain sensitive, active uptake of 86Rb+. The active uptake of 86Rb+ was increased by 18% (p less than 0.05) in the presence of 100 nM insulin, and by 28% (p less than 0.005) in the presence of nM glucagon. These effects were detected as early as 2 min after hepatocyte exposure to either hormone. Half-maximal stimulation was observed with about 0.5 nm insulin and 0.3 nM glucagon. The stimulation of 86Rb+ uptake by insulin occurred in direct proportion to the steady state occupancy of a high affinity receptor by the hormone (the predominant insulin-binding species in hepatocytes at 37 degrees C. For glucagon, half-maximal response was obtained with about 5% of the total receptors occupied by the hormone. Amiloride (a specific inhibitor of Na+ influx) abolished the insulin stimulation of 86Rb+ uptake while inhibiting that of glucagon only partially. Accordingly, insulin was found to rapidly enhance the initial rate of 22Na+ uptake, whereas glucagon had no detectable effect on 22Na+ influx. These results indicate that monovalent cation transport is influenced by insulin and glucagon in isolated rat hepatocytes. In contrast to glucagon, which appears to enhance 86Rb+ influx through the (Na+-K+)-ATPase without affecting Na+ influx, insulin stimulates Na+ entry which in turn may increase the pump activity by increasing the availability of Na+ ions to internal Na+ transport sites of the (Na+-K+)-ATPase. PMID- 6265451 TI - Rotation of cytochrome oxidase in phospholipid vesicles. Investigations of interactions between cytochrome oxidases and between cytochrome oxidase and cytochrome bc1 complex. AB - Cytochrome oxidase was incorporated into lipid vesicles composed of phosphatidylethanolamine-phosphatidylcholine-cardiolipin. Large proteoliposomes of 1,000-15,000 A diameter were prepared by calcium-induced fusion of small vesicles. Rotational diffusion of cytochrome oxidase was measured by detecting the decay of the absorption anisotropy, r(t), after photolysis of the heme a3.CO complex by a vertically polarized laser flash. Because of the large size of the proteoliposomes, there was no contribution of vesicle-tumbling to r(t) over the experimental time range of 5 ms for samples in 60% sucrose. Analysis of r(t) curves was based on a "rotation-about-membrane normal" model. The measurements were used to investigate intermolecular interactions between cytochrome oxidases and between cytochrome oxidase and cytochrome bc1 complex co-reconstituted in the above lipid vesicles. In vesicles of a high lipid to protein ratio (congruent to 27), nearly all cytochrome oxidase molecules are rotating with an approximate rotational relaxation time, phi 1, on the order of 500 microseconds. In contrast, about 20% of cytochrome oxidase is immobile in vesicles with a relatively low lipid to protein ratio (congruent to 5), although phi 1 of the mobile population remains about 500 microseconds. In contrast, about 20% of cytochrome oxidase is immobile in vesicles with a relatively low lipid to protein ratio (congruent to 5), although phi 1 of the mobile population remains about 500 microseconds. The immobilized fraction is presumably due to nonspecific self-aggregation of cytochrome oxidase. The presence of cytochrome bc1 complex does not change r(t) curves significantly, either in the presence or absence of cytochrome c. Previously, we have observed the co-existence of mobile and immobile populations of cytochrome oxidase in bovine heart and rat heart mitochondria (Kawato, S., Sigel, E., Carafoli, E., and Cherry, R. J. (1980) J. Biol. Chem. 255, 5508-5510). The present results suggest that the immobile population of about one-half of cytochrome oxidase could be simply due to nonspecific protein aggregation resulting from the high concentration of enzymes in the inner mitochondrial membrane (lipid to protein ratio, less than or equal to 0.5). We also conclude that there is no specific interaction between cytochrome oxidase and cytochrome bc1 complex in the above large lipid vesicles. A lateral collision-controlled model for electron transfer from cytochrome bc1 complex to cytochrome oxidase through cytochrome c is discussed based on the above results. PMID- 6265452 TI - Escherichia coli recA protein protects single-stranded DNA or gapped duplex DNA from degradation by RecBC DNase. AB - RecA- mutants of Escherichia coli extensively degrade their DNA following UV irradiation. Most of this degradation is due to the recBC DNase, which suggests that the recA gene is involved in the control of recBC DNase in vivo. We have shown that purified recA protein inhibits the endonuclease and exonuclease activities of recBC DNase on single-stranded DNA. The extent of inhibition is dependent on the relative concentration of recA protein, recBC DNase, and the DNA substrate; inhibition is greatest when the concentrations of DNA and recBC DNase are low and the concentrations of recA protein is high. At fixed concentrations of recA protein and recBC DNase, inhibition is eliminated at high concentrations of DNA. In the presence of adenosine 5'-O-(3-thiotriphosphate), an ATP analog which stabilizes the binding of recA protein to both single- and double-stranded DNA, recA protein is a more potent inhibitor of the nuclease activities on single stranded DNA and is a weak inhibitor of the exonuclease activity on double stranded DNA. Inhibition of the latter is enhanced by oligodeoxynucleotides, which stimulate the binding of recA protein to double-stranded DNA. In the presence of adenosine 5'-O-(3-thiotriphosphate), recA protein also inhibits the action of exonuclease I on single-stranded DNA and of lambda exonuclease on double-stranded DNA. These observations are most consistent with the idea that recA protein protects DNA from recBC DNase by binding to DNA. RecA protein also blocks the endonucleolytic cleavage of gapped circular DNA by recBC DNase. Since both recA protein and recBC DNase have the ability under certain conditions to unwind duplex DNA and to displace strands, we looked for evidence that their combined action would enlarge gaps but found no extensive enlargement. D-loops, a putative intermediate in genetic recombination, are effectively protected against the action of recBC DNase by the E. coli single strand binding protein and by recA protein in the presence of adenosine 5'-O-(3-thiotriphosphate). PMID- 6265453 TI - Messenger RNA sequence and primary structure of preproinsulin in a primitive vertebrate, the Atlantic hagfish. PMID- 6265454 TI - Pathways of transcript splicing in yeast mitochondria. Mutations in intervening sequences of the split gene COB reveal a requirement for intervening sequence encoded products. AB - We have studied the transcript processing of the split gene COB (or BOX) in yeast mtDNA, in both wild type and cob- mutants. Using various DNA fragments specific for coding or intervening sequences of this gene, we have determined the composition of splicing intermediates by DNA/RNA hybridization. The pattern of splicing intermediates detected in wild type reveals differing rates of the five splicings resulting in an apparent pathway of processing rather than an absolute order among the five cut and splice events. Effects of mutations in four of the five sequences have been studied. All of them interfere with transcript processing. Some block the excision of the sequence mutated only, but allow other splicing events to occur essentially as in the wild type. They suggest that in these mutants any order of splicings is possible, but that some are preferred. In contrast, other mutations located in four different sequences block several splicings simultaneously and thus suggest the existence of an obligatory order of events. In order to reconcile these findings we discuss the following hypotheses. (i) Some intervening sequences in COB specify products which are involved in transcript splicing; (ii) the biosynthesis of trace amounts of these products occurs on splicing intermediates. Their formation requires a certain order of splicing events to occur on a small number of COB transcripts. (iii) If expressed and functional, the intervening sequence-encoded products, together with other components, act on the bulk of COB transcripts, resulting in the steady state pattern of splicing intermediates observed in wild type. PMID- 6265455 TI - The extracellular cyclic nucleotide phosphodiesterase of Dictyostelium discoideum. Purification and characterization. AB - Two forms of the extracellular cyclic nucleotide phosphodiesterase (EC 3.1.4.17) of Dictyostelium discoideum have been purified. One species has a molecular weight of about 55,000 measured by gel filtration and has been purified to apparent homogeneity. This monomeric form of the enzyme can be resolved by isoelectrofocusing into 4 bands with isoelectric points between 7.5 and 9. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed two bands with molecular weights of 50,000 and 48,000. The second form of the enzyme has been partially purified and has a higher molecular weight (150,000-200,000) and an isoelectric point of about 5. The high molecular weight form of the enzyme is converted to the low molecular weight monomer by isoelectrofocusing in the presence of 6 M urea. Under these conditions the isoelectric point is shifted to that of the monomeric form of the enzyme. The two species are immunologically indistinguishable after urea treatment, and react identically with the cyclic nucleotide phosphodiesterase inhibitor (see the accompanying paper: Franke, J., and Kessin, R. H. (1981) J. Biol. Chem. 256, 7628-7637). The two forms have the same Km and show equal sensitivity to a number of ions, chelators, and low molecular weight cyclic nucleotide phosphodiesterase inhibitors. Tryptic maps of the purified monomeric enzyme and the urea dissociated high molecular weight form revealed no differences. PMID- 6265456 TI - The cyclic nucleotide phosphodiesterase inhibitory protein of Dictyostelium discoideum. Purification and characterization. AB - We have purified the glycoprotein inhibitor of the extracellular cyclic nucleotide phosphodiesterase of Dictyostelium discoideum to apparent homogeneity. The inhibitor has a molecular weight of 47,000 measured by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The interaction of the inhibitor and the cyclic nucleotide phosphodiesterase occurs with 1:1 stoichiometry and with a dissociation constant of about 10(-10) M. Periodate oxidation of the inhibitor or of the enzyme destroys concanavalin A binding ability but does not affect the formation of the enzyme-inhibitor complex. Inhibitor is not produced by cells during logarithmic growth but appears in quantity during stationary phase and after transfer from growth medium to phosphate buffer. PMID- 6265457 TI - Characterization of purified double-stranded RNA-activated eIF-2 alpha kinase from rabbit reticulocytes. PMID- 6265458 TI - Structural comparison of fibronectins from normal and transformed cells. AB - Comparative study of the structures of fibronectins from normal and transformed cells by partial proteolysis as well as by tryptic peptide fingerprinting and analysis of phosphorylation show that: 1) fibronectin molecules from normal and transformed cells probably have very similar primary structures; 2) the phosphorylation of fibronectin is a highly specific and conserved phenomenon; 3) fibronectin from both normal and transformed cells is phosphorylated only on serine residues; 4) although the major sites of phosphorylation in fibronectin are the same in normal and transformed cells, fibronectin from transformed cells appears to be phosphorylated to a much higher extent than that from normal cells. PMID- 6265459 TI - Primary lever masses in infants. AB - Sixteen primary liver masses in infants less than 2 years of age collected from four centers over 12 years included six hepatoblastomas, five benign vascular tumors, three amebic abscesses, a simple hepatic cyst and a calcified cystic hematoma. The diagnostic features of the various lesions are reviewed and the efficient use of the different imaging modalities is discussed. Modern ultrasound techniques offer a diagnostic short-cut in the investigation of primary liver masses in infants and should be done early. PMID- 6265460 TI - Computed tomography of the pterygopalatine fossa. PMID- 6265461 TI - Glycosylation does not determine segregation of viral envelope proteins in the plasma membrane of epithelial cells. AB - Enveloped viruses are excellent tools for the study of the biogenesis of epithelial polarity, because they bud asymmetrically from confluent monolayers of epithelial cells and because polarized budding is preceded by the accumulation of envelope proteins exclusively in the plasma membrane regions from which the viruses bud. In this work, three different experimental approaches showed that the carbohydrate moieties do not determine the final surface localization of either influenza (WSN strain) or vesicular stomatitis virus (VSV) envelope proteins in infected Madin-Darby Canine Kidney (MDCK) cells, as determined by immunofluorescence and immunoelectron microscopy, using ferritin as a marker. Infected concanavalin A- and ricin 1-resistant mutants of MDCK cells, with alterations in glycosylation, exhibited surface distributions of viral glycoproteins identical to those of the parental cell line, i.e., influenza envelope proteins were exclusively found in the apical surface, whereas VSV G protein was localized only in the basolateral region. MDCK cells treated with tunicamycin, which abolishes the glycosylation of viral glycoproteins, exhibited the same distribution of envelope proteins as control cells, after infection with VSF or influenza. A temperature-sensitive mutant of influenza WSN, ts3, which, when grown at the nonpermissive temperature of 39.5 degrees C, retains the sialic acid residues in the envelope glycoproteins, showed, at both 32 degrees C (permissive temperature) and 39.5 degrees C, budding polarity and viral glycoprotein distribution identical to those of the parental WSN strain, when grown in MDCK cells. These results demonstrate that carbohydrate moieties are not components of the addressing signals that determine the polarized distribution of viral envelope proteins, and possibly of the intrinsic cellular plasma membrane proteins, in the surface of epithelial cells. PMID- 6265462 TI - Differential and synergistic actions of nerve growth factor and cyclic AMP in PC12 cells. AB - When a clonal line of rat pheochromocytoma (PC12) was exposed to beta-nerve growth factor (beta NGF), N6, O2-dibutyryl adenosine 3':5' cyclic monophosphate (Bt2cAMP), or a combination of the two, 10, 26, or 70% of the cell clumps, respectively, displayed neurites after 1.d. Increases in the cellular RNA concentration were also found to be additive or greater when both agents were present. Neurites induced by Bt2cAMP alone were not maintained after replacement with beta NGF. The degree of potentiated neurite outgrowth was a function of the time of simultaneous exposure to both agents. The initiation of neurite outgrowth in the presence of Bt2cAMP was independent of RNA synthesis, in contrast to that induced by beta NGF alone. We conclude that beta NGF-induced initiation of morphological differentiation of these cells is not mediated by a cAMP-dependent mechanism. Consideration of Bt2cAMP effects upon other cell lines suggest that Bt2cAMP causes a rapid, but unstable, reorganization of the PC12 cytoskeleton, resulting in the initiation of neurite outgrowth from these cells. In contrast, beta NGF alone achieves a more stable cytoskeleton reorganization by an RNA synthesis-dependent mechanism. PMID- 6265464 TI - Purification of coated vesicles by agarose gel electrophoresis. AB - We have applied agarose gel electrophoresis as a novel step in the purification of clathrin-coated vesicles. Preparations of coated vesicles obtained by sedimentation velocity and isopycnic centrifugation are resolved into two distinct fractions upon electrophoresis. The slower migrating fraction contains smooth vesicles, whereas the faster contains only coated vesicles and empty clathrin coats. The faster mobility of the coated vesicles is primarily caused by the acidic nature of clathrin. Coated vesicles from three different cell types have different mobilities. In each case, however, all of the major polypeptides previously attributed to coated vesicles comigrate with the now homogeneous particles, even though a powerful ATPase activity is completely removed. PMID- 6265463 TI - Stabilization of vasopressin-induced membrane events by bifunctional imidoesters. AB - Vasopressin increases the water permeability of the luminal membrane of the toad bladder epithelial cell. This change in permeability correlates with the occurrence in luminal membranes of intramembrane particle aggregates, which may be the sites for transmembrane water flow. Withdrawal of vasopressin is ordinarily associated with a rapid reduction of water flow to baseline values and a simultaneous disappearance of the particle aggregates. The bifunctional imidoesters dithiobispropionimidate (DTBP) and dimethylsuberimidate (DMS), which cross-link amino groups in membrane proteins and lipids, slow the return of water flow to baseline after vasopressin withdrawal. Cross-linking is maximal at pH 10, and is reduced as pH is lowered. Freeze-fracture studies show persistence of luminal membrane particle aggregates in cross-linked bladders and a reduction in their frequency as water flow diminishes. Fusion of aggregate-containing cytoplasmic tubular membrane structures with the luminal membrane is also maintained by the imidoesters. Reductive cleavage of the central S-S bond of DTBP by beta-mercaptoethanol reverses cross-linking, permitting resumption of the rapid disappearance of the vasopressin effect. Bladders that have undergone DTBP cross-linking and beta-mercaptoethanol reduction respond to a second stimulation by vasopressin. Thus, the imidoesters provide a physiologic and reversible means of stabilizing normally rapid membrane events. PMID- 6265465 TI - Calmodulin triggers the resumption of meiosis in amphibian oocytes. AB - The calcium-binding protein, calmodulin, has been purified from Xenopus laevis oocytes. This 18,500-dalton protein, pl 4.3, has two high-affinity calcium binding sites per mole protein having a dissociation constant of 2.8 x 10(-6) M. Full-grown Xenopus oocytes, arrested in late G2 of the meiotic cell cycle, resumed meiosis when microinjected with 60-80 ng (3-4 pmol) of calmodulin in the form of a calcium-calmodulin complex. The timing of the meiotic events in these recipient oocytes was the same as that normally induced by progesterone. Xenopus ovarian calmodulin stimulated bovine brain phosphodiesterase (PDE) 3- to 10-fold in a calcium-dependent manner, but it had no apparent effect on ovarian PDE activity. A calcium-calmodulin-dependent protein kinase has been isolated from Xenopus oocytes using a calmodulin-Sepharose 4B affinity column. The possible role for this kinase in regulating the G2-M transition in oocytes has been discussed. PMID- 6265468 TI - Role of nuclear glycogen synthase and cytoplasmic UDP glucose pyrophosphorylase in the biosynthesis of nuclear glycogen in HD33 Ehrlich-Lettre ascites tumor cells. AB - Biochemical and autoradiographic evidence show both glycogen synthesis and the presence of glycogen synthase (UDP glucose [UDPG]: glycogen 4-alpha-D glucosyltransferase; EC 2.4.1.11) in isolated nuclei of Ehrlich-Lettre mouse ascites tumor cells of the mutant subline HD33. 5 d after tumor transplantation, glycogen (average 5-7 pg/cell) is stored mainly in the cell nuclei. The activity of glycogen synthase in isolated nuclei is 14.5 mU/mg protein. At least half of the total cellular glycogen synthase activity is present in the nuclei. The nuclear glycogen synthase activity exists almost exclusively in its b form. The Km value for (a + b) glycogen synthase is 1 x 10(-3) M UDPG, the activation constant is 5 x 10(-3) M glucose-6-phosphate (Glc-6-P). Light and electron microscopic autoradiographs of isolated nuclei incubated with UDP-[1-3H]glucose show the highest activity of glycogen synthesis not only in the periphery of glycogen deposits but also in interchromatin regions unrelated to detectable glycogen particles. Together with earlier findings on nuclear glycogen synthesis in intact HD33 ascites tumor cells (Zimmermann, H.-P., V. Granzow, and C. Granzow. 1976. J. Ultrastruct. Res. 54:115-123), the results of tests on isolated nuclei suggest a predominantly appositional mode of nuclear glycogen deposition, without participation of the nuclear membrane system. In intact cells, synthesis of UDPG for nuclear glycogen synthesis depends on the activity of the exclusively cytoplasmic UDPG pyrophosphorylase (UTP: alpha-D-glucose-1-phosphate uridylyltransferase; EC 2.7.7.9). However, we conclude that glycogen synthesis is not exclusively a cytoplasmic function and that the mammalian cell nucleus is capable of synthesizing glycogen. PMID- 6265467 TI - Function of a calmodulin in postsynaptic densities. III. Calmodulin-binding proteins of the postsynaptic density. AB - A method has been developed for binding calmodulin, radioiodinated by the lactoperoxidase method, to denaturing gels and has been used to attempt to identify the calmodulin-binding proteins of cerebral cortex postsynaptic densities (PSDs). Calmodulin primarily bound to the major 51,000 Mr protein in a saturatable manner; secondarily bound to the 60,000 Mr region, 140,000 Mr region, and 230,000 Mr protein; and bound in lesser amounts to a number of other proteins. The major 51,000 Mr calmodulin-binding protein is one of unknown identity. Binding of iodinated calmodulin to these proteins was blocked by EDTA, EGTA, chlorpromazine, and preincubation with unlabeled calmodulin. Calmodulin iodinated by the chloramine-T method, which inactivates calmodulin did not bind to the PSD but bound nonspecifically to histone. Calmodulin did not bind to proteins from a variety of sources for which calmodulin interactions have not been found. Except for three proteins, all of the proteins of synaptic membranes that bind calmodulin could be accounted for by proteins of the PSD which are a part of the synaptic membrane fraction. The major 51,000 M, protein and the corresponding iodinated calmodulin binding were greatly reduced in cerebellar PSDs and this difference between cerebral cortex and cerebellar PSDs is discussed in light of the possible function of calmodulin in synaptic excitatory responses. PMID- 6265466 TI - Function of calmodulin in postsynaptic densities. I. Presence of a calmodulin activatable cyclic nucleotide phosphodiesterase activity. AB - The postsynaptic density (PSD) fraction from canine cerebra cortex was found to contain an endogenous cyclic nucleotide-phosphodiesterase activity that was independent on Mn2+ and/or Mg2+ but not on Ca2+. Maximal activity was obtained at 1 micrometer Mn2+. This cyclic nucleotide phosphodiesterase activity was not decreased upon removal of the calmodulin from the PSD fraction, nor was it increased by the addition of calmodulin to a postsynaptic density fraction deficient in calmodulin. The enzymatic activity could be extracted by sonication, with the soluble enzyme having properties similar to those found in the native structure. Two peaks of cyclic nucleotide phosphodiesterase activities could be obtained after S-300 Sephacryl column chromatography of this soluble fraction: fraction I (excluded peak) and fraction II (215,000 mol wt). The fraction I activity preferred cyclic AMP over cyclic GMP and was not activated by calmodulin. The fraction II activity has an approximately fourfold lower Km for cyclic GMP over cyclic AMP. This fraction II activity was activatable by calmodulin, which increased the Vmax and decreased the Km in the case of both cyclic nucleotides. We conclude that two activities are present in the PSD, one activatable, and one not activatable, by calmodulin. PMID- 6265470 TI - Cell fusion by Semliki Forest, influenza, and vesicular stomatitis viruses. AB - Representatives of three families of enveloped viruses were shown to fuse tissue culture cells together. These were: Semliki Forest virus (SFV, a togavirus), vesicular stomatitis virus (a rhabdovirus), and two myxoviruses, fowl plaque virus and Japan influenza virus (Japan)/A/305/57). Unlike paramyxoviruses, whose fusion activity is known to occur over a broad pH range, fusion by these viruses was restricted to mildly acidic pH. The pH thresholds for the four viruses were 6.0, 6.1, 5.5, and 5.1, respectively. The precursor form of Japan influenza, which is not infectious and which contains the uncleaved hemagglutinin, had no fusion activity. This result suggested a role for the influenza hemagglutinin in the low-pH-dependent membrane fusion activity. Taken together, our results show that low-pH-induced fusion is a widespread property of enveloped animal viruses and that it may play a role in the infective process. The fusion reactions with all four viruses were fast, efficient, and easy to induce. With UV-inactivated SFV, the fusion was shown to be nonlytic and the polykaryons were viable for at least 12 h. 30 ng of SFV/1 x 10(6) BHK-21 cells were required for 50% fusion, and 250 ng sufficed to fuse the entire culture into a single polykaryon. PMID- 6265469 TI - Organization of pp60src and selected cytoskeletal proteins within adhesion plaques and junctions of Rous sarcoma virus-transformed rat cells. AB - The localization of pp60src within adhesion structures of epithelioid rat kidney cells transformed by the Schmidt-Ruppin strain of Rous sarcoma virus was compared to the organization of actin, alpha-actinin, vinculin (a 130,000-dalton protein), tubulin, and the 58,000-dalton intermediate filament protein. The adhesion structures included both adhesion plaques and previously uncharacterized adhesive regions formed at cell-cell junctions. We have termed these latter structures "adhesion junctions." Both adhesion plaques and adhesion junctions were identified by interference-reflection microscopy and compared to the location of pp60src and the various cytoskeletal proteins by double fluorescence. The results demonstrated that the src gene product was found within both adhesion plaques and the adhesion junctions. In addition, actin, alpha-actinin, and vinculin were also localized within the same pp60src-containing adhesion structures. In contrast, tubulin and the 58,000-dalton intermediate filament protein were not associated with either adhesion plaques or adhesion junctions. Both adhesion plaques and adhesion junctions were isolated as substratum-bound structures and characterized by scanning electron microscopy. Immunofluorescence revealed that pp60src, actin, alpha-actinin, and vinculin were organized within specific regions of the adhesion junctions. Heavy accumulations of actin and alpha-actinin were found on both sides of the junctions with a narrow gap of unstained material at the midline, whereas pp60src stain was more intense in this central region. Antibody to vinculin stained double narrow lines defining the periphery of the junctional complexes but was excluded from the intervening region. In addition, the distribution of vinculin relative to pp60src within adhesion plaques suggested an inverse relationship between the presence of these two proteins. Overall, these results establish a close link between the src gene product and components of the cytoskeleton and implicate the adhesion plaques and adhesion junctions in the mechanism of Rous sarcoma virus-induced transformation. PMID- 6265471 TI - Differential effect of monensin on enveloped viruses that form at distinct plasma membrane domains. AB - We have observed a striking differential effect of the ionophore, monensin, on replication of influenza virus and vesicular stomatitis virus (VSV) in Madin Darby canine kidney (MDCK) and baby hamster kidney (BHK21) cells. In MDCK cells, influenza virus is assembled at the apical surfaces, whereas VSV particles bud from the basolateral membranes; no such polarity of maturation is exhibited in BHK21 cells. A 10(-6) M concentration of monensin reduces VSV yields in MDCK cells by greater than 90% as compared with controls, whereas influenza virus yields are unaffected. In BHK21 cells, monensin also inhibits VSV production, but influenza virus is also sensitive to the ionophore. Immunofluorescent staining of fixed and unfixed MDCK monolayers indicates that VSV glycoproteins are synthesized in the presence of monensin, but their appearance on the plasma membrane is blocked. Electron micrographs of VSV-infected MDCK cells treated with monensin show VSV particles aggregated within dilated cytoplasmic vesicles. Monensin-treated influenza virus-infected MDCK cells also contain dilated cytoplasmic vesicles, but virus particles were not found in these structures, and numerous influenza virions were observed budding at the cell surface. These results indicate that influenza virus glycoprotein transport is not blocked by monensin treatment, whereas there is a block in transport of VSV G protein. Thus it appears that at least two distinct pathways of transport of glycoproteins to the plasma membrane exist in MDCK cells, and only one of them is blocked by monensin. PMID- 6265472 TI - Dunce mutants of Drosophila melanogaster: mutants defective in the cyclic AMP phosphodiesterase enzyme system. AB - The cyclic AMP and cyclic GMP phosphodiesterase activities present in flies of six mutant strains of the dunce gene and in the parent wild-type strains are characterized. All of the mutants exhibit aberrant cyclic AMP metabolism. The mutant strains dunceM14, dunceM11, and dunceML appear to be amorphic, because they completely lack the cAMP-specific phosphodiesterase normally present in adult flies. These strains exhibit extremely high levels of cAMP. The mutant strains dunce1, dunce2, and dunceCK are hypomorphic and exhibit reduced levels of the cAMP-specific phosphodiesterase. These strains exhibit less marked increases in cAMP content compared with the three amorphic strains. The dunce2 strain possesses a residual enzyme activity that exhibits anomalous kinetics compared with those of the normal enzyme. The possibility that the dunce locus is the structural gene for the cAMP-specific phosphodiesterase is discussed. PMID- 6265473 TI - Integrity of mitochondria in a mammalian cell mutant defective in mitochondrial protein synthesis. AB - A defect in mitochondrial protein synthesis has previously been identified in the respiration-deficient Chinese hamster lung fibroblast mutant V79-G7. The present work extends the characterization of this mutant. A more sensitive analysis has shown that mutant mitochondria synthesize all mitochondrially encoded peptides, but in significantly reduced amounts. This difference is also seen when isolated mitochondria are tested for in vitro protein synthesis. To distinguish between a defect in the translational machinery and a defect in the transcription of mitochondrial DNA, we investigated the synthesis of the 16S and 12S mitochondrial rRNA species and found them to be made in normal amounts in G7 mitochondria. These rRNA species appear to be assembled into subunits whose sedimentation behavior is virtually indistinguishable from that of the wild-type subunits. We also examined the consequences of the defect in mitochondrial protein synthesis on mutant cells and their mitochondria-utilizing techniques of electron microscopy, two-dimensional gel electrophoresis and immunochemical analysis. G7 mitochondria have a characteristic ultrastructure distinguished by predominantly tubular cristae, but the overall biochemical composition of mitochondrial membrane and matrix fractions appears essentially unaltered except for the absence of a few characteristic peptides. Specifically, we identify the absence of two mitochondrially encoded subunits of cytochrome c oxidase on two dimensional gels and demonstrate a drastic reduction of both cytoplasmically and mitochondrially synthesized subunits of enzyme in immunoprecipitates of G7 mitochondria. PMID- 6265474 TI - Cell cycle changes in the adenylate cyclase of C6 glioma cells. AB - The adenylate cyclase of C6 glioma cell cultures was characterized for sensitivity to the beta-adrenergic agonist isoproterenol, as well as fluoride, and GTP as a function of the cell cycle. The mitotic phase of the cell cycle was emphasized because both the basal cellular cyclic AMP level and the intact C6 cell's capacity to accumulate cyclic AMP in response to isoproterenol decreased during mitosis. Basal and stimulated adenylate cyclase activities in mitotic cells were decreased relative to the enzyme activities in the G1, S, and G2 phases of the cell cycle. Analysis of the beta-adrenergic receptor using the radioligand(-)[3H]dihydroalprenolol showed that neither ligand affinity nor receptor density changed during the cell cycle, indicating that the reduced adenylate cyclase activity of the mitotic C6 cell was not caused by alterations in this hormone receptor. The reduction in the mitotic cell's basal adenylate cyclase activity was more prominent than the decrease in isoproterenol-, fluoride, or GTP-stimulated activities suggesting that the effectiveness of these enzymes activators (i.e., the efficiency of the coupling mechanism) was not attenuated during mitosis. These studies indicate that the intrinsic catalytic capacity (not the beta-adrenergic receptor or the coupling mechanism) of the C6 adenylate cyclase complex is reduced during mitosis and contributes to the mitotic cell's inability to accumulate and maintain the cyclic AMP concentration at the interphase level. PMID- 6265475 TI - Substrate adhesion of rat hepatocytes: a comparison of laminin and fibronectin as attachment proteins. AB - In previous studies rat hepatocytes have been shown to adhere to substrates composed of collagen or fibronectin. In the present communication, the basement membrane protein laminin is reported to mediated the attachment and spreading of hepatocytes. The cell attachment-mediating activity of laminin was compared with that of fibronectin. The activity of fibronectin was heat sensitive, whereas laminin retained its activity after boiling. On the other hand, reduction and alkylation or periodate oxidation of the proteins affected only the cell attachment activity of laminin. Preincubation of cells with soluble fibronectin inhibited initial cell attachment to fibronectin but not to laminin substrates, and, reversely, soluble laminin selectively inhibited cell attachment to laminin. These results suggest that attachment of cells to substrates of the two proteins involves different cellular receptors recognizing distinct and nonidentical structures in the proteins. PMID- 6265476 TI - The expression of glial fibrillary acidic protein in a rat cerebellar cell line. AB - A rat cerebellar cell line, WC5, derived by transformation with Rous sarcoma virus, which is temperature-sensitive for transformation (ts-RSV), can be induced to express glial fibrillary acidic protein (GFAP). Immunofluorescence, radioimmune assay, and electron microscopy studies show that GFAP is expressed in WC5 cells grown at the nonpermissive temperature (NPT), but not at the permissive temperature (PT) for transformation. GFAP is first detectable about 3 days after incubating cells at the NPT, and reaches an apparent plateau by the seventh or eighth day. The expression of GFAP is reversible; shifting cells from the NPT to the PT causes a dramatic decrease in GFAP after 96 hr. In order to determine if the expression of GFAP is linked to the temperature-sensitive transforming activity of the viral src gene product, phenotype revertants of WC5 were established. By the criteria of morphology and growth in agar, the revertant lines, in contrast to the parent cell line WC5, were shown to exhibit a transformed phenotype at both the NPT and PT. Immunofluorescence studies on several of the revertant cell lines show that they do not express GFAP at either the PT or NPT. These findings suggest that the expression of GFAP in WC5 is linked to the expression of the src gene product. The advantage of using ts-RSV to derive neural cell lines which exhibit differentiated properties is discussed. PMID- 6265477 TI - Regulation of glucose utilization in chick embryo fibroblasts by bicarbonate ion. AB - The amount of glucose consumed by chick embryo fibroblasts in primary culture is strongly influenced by the presence of bicarbonate ion in the culture medium. Cells grown on glucose at physiologic concentration (5.5 mm) and in the absence of bicarbonate ion have a reduced rate of glucose utilization when compared to their counterparts cultivated in medium containing the usual 25 mM bicarbonate. The presence or absence of bicarbonate is without effect on chick embryo fibroblast proliferation over a 6-day growth period. Both lactic acid accumulation per mole of glucose consumed and the utilization of glutamine increase as a function of bicarbonate ion in the growth medium. PMID- 6265478 TI - Further studies of hormone-sensitive sodium and potassium transport in red cells from developing chick embryos. AB - Sodium and potassium transport in the definitive series of chick embryo red cells changes significantly, both qualitatively and quantitatively, during maturation. Sodium efflux and potassium influx consist of three parts: a ouabain-sensitive, a furosemide-sensitive, and a ouabain-furosemide-insensitive component. In chick red cells of most ages, the ouabain-sensitive and furosemide-sensitive parts of the cation fluxes do not overlap. Cation transport in the more mature red cells is increased significantly by epinephrine, whereas cation transport in red cells from younger embryos is stimulated much less. This is a beta-adrenergic effect of epinephrine and is mediated by cyclic AMP. The relative lack of response in younger embryos is not due to the absence of beta-adrenergic receptor or the lack of production of cyclic AMP. Ouabain has no effect on the hormone-sensitive sodium or potassium transport. On the other hand, furosemide nearly completely abolishes the effect of epinephrine. In addition, there is a good correlation between furosemide-sensitive components of both sodium and potassium transport and the epinephrine-sensitive component. Furosemide has no effect on cyclic AMP levels in the presence or absence of epinephrine. This suggests that furosemide may act directly on the cation transport system. In the red cells from younger embryos, furosemide-sensitive units are present but cannot be fully activated by epinephrine. Therefore, the lack of the hormone effect on cation movements in these cells is consistent with the view that the appropriate units are present, but do not respond fully to intracellular cyclic AMP levels. PMID- 6265479 TI - Epstein-Barr virus in nontumorigenic and tumorigenic nasopharyngeal carcinoma (NPC) somatic cell hybrids. AB - Somatic cell hybrids between mouse fibroblasts and human cells derived from nasopharyngeal carcinoma (NPC) biopsies or NPC tumors propagated in nude mice were examined for the expression of the Epstein-Barr nuclear antigen (EBNA), retention of Epstein-Barr viral (EBV) DNA, and tumorigenicity in nude mice. In all hybrids the expression of EBNA correlated with the detection of EBV-DNA. After more than 2 years in culture, the hybrids examined retained similar amounts of EBV-DNA when compared to previously published data. Retention of EBV-DNA did not correlate with the presence of any particular human chromosome. Use of either rodent cell lines, clone 1D or IT-22, did not affect the retention nor loss of EBV-DNA. For tumorigenicity studies, NPC cells were fused with IT-22 cells and injected into nude mice. Tumor formation did not depend on the presence or absence of EBNA and detectable EBV-DNA sequences; tumorigenicity in these studies could not be correlated with the presence of any particular human chromosome or the origin of the NPC biopsy. PMID- 6265481 TI - [Associated granular cell tumor and esophageal cancer (author's transl)]. AB - The first reported case of an association of Abrikossof's tumor and a cancer in the esophagus is described. After a general view of the published literature on these tumors, their clinical and pathological characteristics are outlined, and their histogenesis envisaged in relation to histochemical and ultrastructural findings. Therapeutic methods and means of follow-up surveillance are defined. PMID- 6265482 TI - Determination of 5'-nucleotidase by automated ion-exchange column chromatography. PMID- 6265480 TI - Reverse transformation of vole cells transformed by avian sarcoma virus containing the src gene. AB - Vole cells transformed by avian sarcoma virus carrying the src gene lose their fibroblastic morphology, the organized cytoskeletal system of the normal fibroblastic cell, the typical fibronectin deposit around the cell membrane, and the ability to shut off multiplication when suspended in liquid medium. All of these transformation characteristics are reversed by treatment with cAMP derivatives. Moreover, the cAMP treatment does not cause loss of activity of the src gene product. These data imply that cAMP exerts its effect at or after the point in the metabolic pathway affected by the src gene product, pp60src. Presumably, the decision to adopt the transformed or the normal state is determined by the degree to which the src gene or cAMP-mediated kinase activities respectively predominante in the cell. The development of all four transformation characteristics as a result of introduction of the src gene, and their coordinate reversal by cAMP derivatives, supports the previous thesis that in the normal vole or CHO fibroblast all four properties are part of a common regulatory system. PMID- 6265483 TI - Determination of the anti-tumor agent, 10-chloro-5-(2-dimethylaminoethyl)-7h indolo[2,3-c] quinoline-6(5h)-one. HCl in blood or plasma by high-performance liquid chromatography. AB - A sensitive and specific high-performance liquid chromatographic assay was developed for the determination of 10-chloro-5-(2-dimethylaminoethyl)-7H-indolo [2,3-C] quinolin-6(5H) one [I] in blood or plasma with an overall recovery of 100.3 +/- 9.1% and a limit of quantitation of 1.0 ng per ml of blood or plasma. the assay was used to determine blood concentrations of the drug in the rat following oral administration by intubation of a 1.17-mg dose of [I] . HCl. PMID- 6265484 TI - Production of pregnancy-specific beta 1-glycoprotein by cultured placental cells. AB - The synthesis of pregnancy-specific beta 1-glycoprotein (PS beta G) was studied in simian virus 40 temperature-sensitive A mutant-transformed human first trimester and term placental cells. At the permissive temperature (33 C, transformed phenotype), they produced low levels of PS beta G. At the restrictive temperature (40 C), the transformed phenotype was lost, and the production of PS beta G was greatly enhanced. The PS beta G produced by these transformed placental cells resembled the purified placental PS beta G by several criteria. Both cell and placental PS beta G bound to Concanavalin A-Sepharose and were, therefore, glycoproteins. The cell PS beta G cochromatographed with placental PS beta G on a Bio-Gel A-0.5m column. Furthermore, the slopes of the dose-response curves for the cell PS beta G were indistinguishable from that for placental PS beta G. The synthesis of PS beta G at both 33 and 40 C in these placental cells was greatly induced by sodium butyrate and 5-bromo-2'-deoxyuridine. Sodium butyrate was a more effective inducer at 33 C, whereas BrdUrd appeared to be a better inducer at 40 C. PMID- 6265486 TI - Histamine and human parathyroid adenoma: effect on adenosine 3',5'-monophosphate accumulation in vitro. AB - We studied in vitro the presence of histamine and the effect of histamine and its antagonists on cAMP accumulation in parathyroid tissue (parathyroid adenoma or hyperplasia) from patients with primary hyperparathyroidism. Parathyroid adenomatous tissue contained 11.2 +/- 2.9 ng histamine/g wet weight (approximately 2 X 10(-5) M), as determined by a specific radioenzyme assay. Histamine caused a prominent increase in cAMP accumulation in parathyroid tissue slices in a dose-dependent manner, with half-maximal stimulation being achieved at 5 X 10(-6) M and maximal stimulation occurring at 10(-4) M histamine. The histamine H2 receptor antagonists, cimetidine and metiamide, caused profound inhibition of histamine-stimulated cAMP accumulation in the parathyroid tissue. Pyrilamine, an H1 antagonist, also inhibited histamine-stimulated cAMP accumulation. Isoproterenol, a beta-adrenergic agonist, elicited marked elevation of cAMP, and its stimulatory effect was blocked by propranolol, but the effects of histamine on cAMP levels in parathyroid tissue were not blocked by propranolol. Histamine significantly stimulated (an increase of 50%) the release of immunoreactive parathyroid hormone. The present observations demonstrate that parathyroid adenomatous tissue has a relatively high content of histamine, and the release of immunoreactive parathyroid hormone from this tissue. The effects of antagonists suggest that histamine stimulates cAMP accumulation in the parathyroid adenomatous tissue by an action on both H2 and H1 histamine receptors. PMID- 6265485 TI - Regional distribution of cholecystokinin-like immunoreactivity in the human brain. PMID- 6265487 TI - Overproduction of sodium-retaining steroids by the zona glomerulosa is adrenocorticotropin-dependent and mediates hypertension in dexamethasone suppressible aldosteronism. AB - Dexamethasone suppressed urinary aldosterone to less than 1.5 micrograms/day in 1 2 days and lowered blood pressure in a woman and in her 2 1/2-yr-old daughter, both of whom have hypertension and hyporeninemia and are members of a kindred with dexamethasone-suppressible aldosteronism. ACTH given for 7 days produced a sustained increase in aldosterone production and a rise in blood pressure in both patients. The abnormal suppression with dexamethasone and further stimulation with ACTH indicate that the aldosteronism is ACTH-dependent in this disorder. The cause of the ACTH-dependence of aldosterone production in this disorder is unknown but may represent continued stimulation rather than the usual (secondary) inhibition by ACTH of 11-hydroxylation and 18-hydroxylation in zone glomerulosa cells. Blood pressure was normal during treatment with spironolactone and during pregnancy, when the action of aldosterone and other similar steroids was presumably blocked by an increased production of progesterone; this suggests that the hypertension is dependent upon sodium-retaining steroids such as aldosterone. Aminoglutethimide given during treatment with ACTH decreased urinary aldosterone and blood pressure and increased PRA, with minimal effects on plasma cortisol or urinary 17-hydroxycorticosteroids. These results provide additional evidence that aldosterone, acting alone or in conjunction with other steroids synthesized by the zona glomerulosa, mediates the hypertension and hyporeninemia of dexamethasone-suppressible aldosteronism. PMID- 6265488 TI - Excessive circulating large molecular weight immunoreactive glucagon components in subjects with the idiopathic postprandial syndrome. AB - The glucagon RIA measures several molecular components in human plasma. Clinical disorders have been described associated with abnormal elevations of certain of these components. This report documents another clinical disorder, the idiopathic postprandial syndrome, which also appears associated with excessive circulating large molecular weight immunoreactive glucagon (IRG) components. During studies of glucose homeostasis in subjects with apparent idiopathic postabsorptive hypoglycemia, 80 subjects were evaluated using oral glucose tolerance tests; 18 subjects were found to have clinical and laboratory findings consistent with the disorder, and of these, 3 had markedly elevated basal total plasma IRG levels. Plasma IRG responses in the subjects after oral glucose or mixed meals were variable. Physical characterization of the excessive large molecular weight IRG components revealed molecular weight estimates of 300,000 and 345,000 daltons in 2 subjects and of more than 200,000 daltons in the third subject. The origin and chemical nature of this material is uncertain. None of these subjects had evidence for a glucagonoma, as supported by the virtual absence of detectable levels of native (3500-dalton) glucagon after gel filtration. Since the origin of the idiopathic postprandial syndrome as well as the origin and chemical nature of large molecular weight IRG components are unknown, the association of these two findings remains unclear but is clinically important in the differential diagnosis of the glucagonoma syndrome. PMID- 6265489 TI - Evidence for reduced 3 beta-ol-hydroxysteroid dehydrogenase activity in some hirsute women thought to have polycystic ovary syndrome. AB - Congenital adrenal hyperplasia due to 3 beta-ol-hydroxysteroid dehydrogenase (3 beta-ol) deficiency is usually lethal. A partial deficiency in 3 beta-ol has been suggested in some women presenting with androgen excess. In this study, 24 women were investigated who had hirsutism and oligomenorrhea and high serum delta 5 androgens compared to delta 4 androgens. Of these women, 9 had significantly elevated 17-hydroxypregnenolone (17 Preg) to 17-hydroxyprogesterone (17 Prog) ratios when compared to controls under basal conditions. On further testing of 9 women with ACTH, 4 had significantly elevated 17 Preg to 17 Prog ratios. Eight women had elevated ratios of dehydroepiandrosterone sulfate to androstenedione, 4 had elevations of androstenediol (Adiol) to testosterone (T), and 4 had abnormal 17 Preg to cortisol ratios. Only 3 women out of the original 24 selected for study had elevated ratios for all 4 different steroid pairs measured. 17 Prog was normal in these women with 3 beta-ol deficiency in contradistinction to the high levels normally observed in women with congenital adrenal hyperplasia due to 21- or 11-hydroxylase deficiency. It is suggested that the cause of androgen excess in these women is high circulating levels of Adiol and, in part, the slightly elevated unbound T levels in these women. In conclusion, a subtle, incomplete form of 3 beta-ol deficiency may exist in adult women and is manifest by high delta 5 androgens such as dehydroepiandrosterone sulfate and Adiol and normal delta 4 androgens such as androstenedione and T. PMID- 6265490 TI - The control of steroidogenesis by human fetal adrenal cells in tissue culture. II. Comparison of morphology and steroid production in cells of the fetal and definitive zones. AB - Preparations of dispersed human fetal adrenal cells from the inner third of the gland and from the subcapsular area were maintained in culture, and their ultrastructure and steroid production were studied. The former type of preparation contained only fetal zone cells, while the latter contained definitive zone cells together with varying numbers of fetal zone cells. Both types could be cultured with equal ease, but during short term culture, fetal and definitive zone cells became morphologically indistinguishable. The patterns of steroid production and, in particular, the relative production of delta 4,3 ketosteroids and delta 5,3 beta-hydroxysteroids were similar in both preparations, as were their dose-response relationships during incubation with alpha ACTH-(1-24). Although considerable variability in total steroid production was observed between cells from different adrenal glands, in no specimen was any evidence for functional zonation of the fetal adrenal cortex observed in vitro. The results suggest that the apparently unique histological appearance and function of the fetal adrenal cortex may only reflect intense stimulation by ACTH secondary to the combined influences of a rapid cortisol MCR and of some inhibitor of fetal adrenal 3 beta-hydroxysteroid dehydrogenase activity. PMID- 6265491 TI - Human anencephalic adrenal tissue: low density lipoprotein metabolism and cholesterol synthesis. PMID- 6265492 TI - Secretion of testosterone-estradiol-binding globulin by a human hepatoma-derived cell line. AB - Using a sensitive radioimmunoassay for testosterone-estradiol-binding globulin (TeBG) we demonstrate that a human hepatoma-derived cell line secretes a protein which: (a) is immunologically indistinguishable from TeBG; (b) has the same Stokes radius as TeBG; (c) is absorbed by concanavalin A in the same way as TeBG in normal plasma. PMID- 6265494 TI - Freeze-dried erythrocytes for an indirect hemagglutination test for detection of cytomegalovirus antibodies. AB - An indirect hemagglutination test with lyophilized, fixed, tanned, and cytomegalovirus (CMV)-sensitized sheep erythrocytes for the detection of CMV antibodies is reported. To avoid nonspecific hemagglutination, cells were fixed with glutaraldehyde or Formalin directly in whole blood. The lyophilized, CMV sensitized erythrocytes obtained by this technique were stable up to 9 months at 37 degrees C and retained the same reactivity at fresh, CMV-sensitized cells. Indirect hemagglutination performed with lyophilized, sensitized cells was highly efficient in detecting CMV-antibodies as compared with complement fixation and enzyme immunoassay. PMID- 6265493 TI - Clinical manifestations of diarrhea in calves infected with rotavirus and enterotoxigenic Escherichia coli. AB - The susceptibility of gnotobiotic, colostrum-derived, or suckling calves to four bovine rotavirus isolates was found to be age dependent. Calves older than 7 days remained clinically normal, although they excreted virus in their feces and subsequently developed antibody against the virus, Enterotoxigenic Escherichia coli, fed to gnotobiotic, colostrum-deprived, or suckling calves ranging in age from a few hours to 26 days old, only caused diarrhea in animals younger than 24 h old. In contrast, diarrhea was consistently induced in 1- and 2-week-old calves infected with both enterotoxigenic E. coli and rotavirus. In general, diarrhea appeared after a rotavirus incubation period of approximately 3 days and was independent of the order in which the two microbial agents were given, the age of the calf, or the level of circulating rotavirus antibodies. The disease episode coincided with the excretion of rotavirus, rather than enterotoxigenic E. coli, in the feces. Infection with enterotoxigenic E. coli became established within 24 h of inoculation, and in older calves enterotoxigenic E. coli was often excreted in very small numbers and for a longer period than rotavirus. PMID- 6265495 TI - Studies of the mechanism by which 3,5,3'- triiodothyronine stimulates 2 deoxyglucose uptake in rat thymocytes in vitro. Role of calcium and adenosine 3':5'-monophosphate. AB - The present experiments were designed to explore the mechanism whereby 3,5,3' triiodothyronine (T3) stimulates the uptake of 2-deoxy-D-glucose (2-DG) in rat thymocytes in vitro. Addition of T3 evoked a transient, dose-related increase in cellular cyclic (c) AMP concentrations, evident within 5 min. followed soon by an increase in 2-DG uptake. The effects of T3 on both cAMP concentration and 2-DG uptake were dependent upon the presence of extracellular calcium. Epinephrine also induced a sequential increase in thymocyte cAMP concentration and 2-DG uptake. These responses were more prompt than those to T3, but were calcium independent. As with their combined effects on 2-DG uptake, T3 and epinephrine produced synergistic or additive effects on cellular cAMP concentration. Dibutyryl cAMP also stimulated 2-DG uptake, an effect that was more prompt than that of epinephrine, and like that of epinephrine, was calcium independent. Prior or simultaneous addition of L-alprenolol (10 microM), which, we have previously shown, blocks the effect of both T3 and epinephrine on 2-DG uptake, also blocked the increase in thymocyte cAMP concentration induced by these agents. In contrast, L-alprenolol failed to block the increase in 2-DG uptake produced by dibutyryl cAMP. On the basis of these observations we suggest that T3 increases 2 DC uptake in the rat thymocyte by increasing the cellular concentration of cAMP, which then acts to enhance sugar transport. The increase in 2-DC uptake induced by epinephrine is also mediated by an increase in cAMP concentration. The greater response of cellular cAMP concentration to T3 and epinephrine when added together than to either agent added alone may explain their synergistic action to increase 2-DG uptake. We suggest that these actions of T3 and epinephrine are both initiated at the level of the plasma membrane. PMID- 6265496 TI - Release of angiotensin converting enzyme by the lung after Pseudomonas bacteremia in sheep. AB - We studied release of angiotensin-converting enzyme (ACE) by the lung after acute injury associated with an increase in pulmonary vascular permeability. In eight adult sheep with chronic lung lymph fistulas, we measured lymph flow (QL), and both ACE activity and total protein content in lymph and plasma under base-line conditions and during 24 h after an infusion of live pseudomonas organism. Under base-line conditions, ACE activity in plasma was 4.93 +/- 0.43 U/ml (mean +/- SEM). The [lymph]/[plasma] ([L]/[P]) ratio for ACE was 0.93 +/- 0.18, compared with a ratio of 0.79 +/- 0.08 for albumin (mean +/- SD). We estimated the molecular weight of ovine ACE to be 145,000 by gel chromatography. Predicted [L]/[P] ratio for a molecule this size is 0.51. Thus, a substantial fraction of ACE activity detected lung lymph under base-line conditions (11.1 +/- 6.2 U/h; mean +/- SD) originated in the lung, and did not diffuse passively from plasma. After pseudomonas infusion, endothelial injury was demonstrated by a rise in pulmonary vascular clearance for total protein (Crp = QL X [L]/[P]). Crp = 3.1 +/ 0.6 ml/h before pseudomonas bacteremia, and rose to 6.7 +/- 1.2 ml/h by 2 h after onset of the infusion (means +/- SEM, p less than 0.05). Crp remained significantly elevated for at least 10 h after the infusion. Release of ACE into lung lymph doubled after acute lung injury and equaled 22.3 +/- 13.8 U/h at 4 h after onset of the infusion. ACE secretion into lung lymph had returned to baseline levels by 24 h after bacteremia. We did not observe a significant rise in plasma ACE activity after acute lung injury. Pseudomonas bacteremia in sheep results in acute, reversible lung injury associated with increased pulmonary vascular permeability, and increased release of ACE by the lung. Failure to detect a rise in plasma ACE content might result from dilution in the large vascular pool or rapid catabolism of the enzyme at some site distant from the lung. PMID- 6265497 TI - In vivo comparison of cerebral tissue PO2 and cytochrome aa3 reduction-oxidation state in cats during hemorrhagic shock. AB - To assess the adequacy of oxygen availability and utilization within the cerebral cortex in vivo, we have measured the partial pressure of oxygen in tissue (PtO2), as well as the reduction oxidation state of cytochrome c oxidase (cyt aa3) during shock induced by slow or rapid hemorrhage in anesthetized cats. PtO2 was measured with pyrenebutyric acid-generated fluorescence in cerebral cortical cells. Cyt aa3 redox state was measured by the absorption of monochromatic light at 605 nm absorption peak of the enzyme reflected from the same cortical field. The PtO2 remained within the normal range until either 30 +/- 1.5 ml blood/kg was removed or the mean arterial pressure fell by 70 +/- 5% of base line. Beyond either point, the PtO2 fell rapidly to a low value approximating zero. By contrast, the reduction of cyt aa3 began early when as little as 5 ml blood/kg was removed. Thereafter, the shift toward reduction was progressive and continuous with a slow rate at first and a rapid rate later. This accelerated rate of cyt aa3 reduction preceded the rapid fall of PtO2. We concluded that, under these experimental conditions, cyt aa3 reduction is a much earlier and more sensitive indicator of perturbed intracellular aerobic metabolism due to hemorrhage that is PtO2. PMID- 6265498 TI - Impaired beta adrenergic receptor binding and function in cystic fibrosis neutrophils. AB - Cystic fibrosis (CF), a genetic disease characterized by abnormalities of exocrine gland and mucociliary function, has recently been shown to be associated with abnormal adrenergic and cholinergic physiologic responses in addition to decreased beta adrenergic-induced cyclic AMP generation in human leukocytes. In this study we have attempted to elucidate the nature of this hyporesponsiveness by assessing beta adrenergic receptor number and affinity (KD) in the intact neutrophil using the antagonist ligand [3H] dihydroalprenolol and cyclic AMP responses to isoproterenol in addition to histamine, and prostaglandin E1 in CF subjects, CF obligate heterozygotes (CFH), and normal control subjects. CF patients had significantly less (p less than 0.025) cyclic AMP stimulation above basals levels with isoproterenol (0.1 microM to 0.1 mM), compared with control values, but no consistent differences between groups were noted with histamine or PGE1. CF neutrophils had significantly fewer (p less than 0.005) beta adrenergic receptors per neutrophil (398.0 +/- 54.2 vs. 819.4 +/- 67.2) compared with control neutrophils, but the KD (0.740 +/- 0.11 vs. 0.630 +/- 0.05 nM) did not differ significantly (p greater than 0.05). There was no correlation between clinical severity and either cyclic AMP generation or dihydroalprenolol binding (r = 0.27 and 0.24, respectively, p greater than 0.05). The CFH group had approximately 50% of the cyclic AMP stimulation compared with controls, but the number (909.8 +/- 89.3) and KD (0.710 +/- 0.09 nM) of their beta adrenergic receptors were indistinguishable from control subjects. These findings suggest "down regulation" of the beta receptor in the CF patient. The cause of this remains unknown. Although the etiology of the decreased cyclic AMP responses in CFH was not due to decreased beta adrenergic receptors as assessed by antagonist ligand binding, further studies inthe CFH group to include agonist binding, receptor-adenylate cyclase coupling, intrinsic adenylate cyclase activity, and catecholamine metabolism may help determine the basic cause of beta adrenergic hyperesposiveness in both CFH and CF. PMID- 6265501 TI - Sonography of islet cell tumor of the pancreas: report of two cases. PMID- 6265500 TI - Extracellular proton release by stimulated neutrophils. AB - We have tried to elucidate the mechanism of phagosome acidification in human neutrophils. Assuming that phenomena occurring at the plasma membrane reflect reactions in the phagocytic vacuoles, we have stimulated human neutrophils with agents that induce a "respiratory burst," and we have measured the release of protons into the extracellular medium. Phorbol myristate acetate, N-formyl methionyl-leucyl-phenylalanine and serum-opsonized zymosan particles each caused a rapid release of protons, concomitant with the increase in oxygen consumption. The stimulated release of protons was strictly coupled to the increase respiration of the cells, because inhibition of the respiration of either anaerobiosis, chlorpromazine, or glycolytic inhibitors also inhibited the release of protons. Also, in the presence of the above-mentioned stimulating agents, neutrophils from three patients with chronic granulomatous disease enhanced neither respiration not proton release. In normal cells, the ratio of deltaH+/ deltaO2 was 1.04 +/- 0.19 (mean +/ SD, n = 13). The mechanism of this proton release is not clear. The amount of lactic and carbonic acid produced by stimulated neutrophils was inadequate to explain the amount of protons released. Perhydroxyl radicals were also ruled out as the source of the protons. Because the cells did not release measurable amounts of phosphate ions, a phosphate hydroxyl-ion antiport was also excluded. Finally, the lack of any effect of uncouplers renders it unlikely that a respiration-driven proton gradient is built up across the plasma membrane. PMID- 6265499 TI - NADH cytochrome b5 reductase activity in lymphoid cell lines. Expression of the defect in epstein Barr virus transformed lymphoblastoid cell lines from patients with recessive congenital methemoglobinemia. AB - Recessive congenital methemoglobinemia (RCM) is due to the homozygous deficiency of NADH-cytochrome b5 reductase (EC 1.6.2.2.). In type I disease, in which the patients are only methemoglobinemic, the enzyme defect is fully expressed in the erythrocytes, whereas the leukocytes are much less affected. In type II disease, in which the patients are, in addition, mentally retarded, the defect is generalized to all the tissues including cultured fibroblasts. In the present study we have investigated Epstein-Barr virus (EBV) transformed lymphoid cell lines (LCL) derived from patients with both types of cytochrome b5 reductase deficiency and from nondeficient individuals. The total cytochrome b5 reductase activity of the control LCL was found to be similar whatever the LCL origin, except for one lymphoma line (Daudi). The enzyme from the control LCL (c 252/B 95) was found to be immunologically related to the human soluble erythrocyte cytochrome b5 reductase, indicating that it is the product of the same gene: the DIA1 (diaphorase) locus. The LCL derived from one patient with the type I disease and two patients with the type II disease were investigated.l In the former the defect was expressed to a lesser degree than in the cases with mental retardation in which the defect was much pronounced, and involved both the mitochondrial and the microsomal fraction. This indicated that all the subcellular forms of the cytochrome b5 reductase are under the same genetic control. Altogether, these data show that the LCL are a favorable material for studying both types of cytochrome b5 reductase deficiency and for investigating in depth the molecular aspects of this metabolic disease. PMID- 6265502 TI - Demonstration of papilloma virus particles in cervical and vaginal scrape material: a report of 10 cases. AB - The finding of virus particles by transmission electron microscopy (TEM) in fixed cervical and vaginal scrape material and their identification as papilloma viruses by negative staining is described. The colposcopic, cytological, and histological appearances in a group of 10 patients in whom virus particles were seen are discussed and the possibly considered of an association between papilloma virus infection and the development of cervical intraepithelial neoplasia (CIN) and multifocal intraepithelial neoplasia of the female lower genital tract. PMID- 6265503 TI - Condylomata of the uterine cervix and koilocytosis of cervical intraepithelial neoplasia. AB - In 202 women with koilocytotic atypia in cervical smears, 136 had predominantly small condylomata of the uterine cervix, and 66 had cervical intraepithelial neoplasia (CIN) of varying degree either with koilocytosis of the neoplasia or associated with condylomata. Koilocytosis correlated well with the histological diagnosis of condylomata, but occasionally it obscured the cytological evidence of CIN. Human papilloma virus particles were found in the cells of condylomata in 10 cases and in those of CIN II with koilocytosis in two cases of 21 examined ultrastructurally. There was evidence that the condyloma of the uterine cervix is a well-defined morphological entity and also that cytopathie changes similar to those seen in condylomata are present in some cases of CIN. PMID- 6265504 TI - Enzyme-linked immunosorbent assay for measurement of antibody against cytomegalovirus and rubella virus in a single serum dilution. AB - Enzyme-linked immunosorbent assays (ELISA) were developed for quantifying cytomegalovirus (CMV) and rubella antibodies using a single serum dilution (1/800) in conjunction with a standard curve. A near linear relation was found between the logarithms of absorbance values of sera at a dilution of 1/800 and the titres as determined by an end point dilution ELISA. The reproducibility of the single dilution ELISA was good; the within-test coefficients of variation averaged 7.5% for CMV antibody and 12.4% for rubella antibody. A close correlation was found between ELISA and complement-fixing (CF) antibody titres to CMV and between ELISA and haemagglutination-inhibition (HI) antibody titres to rubella virus. The titres in ELISA were 200 to 1000 times higher than in CF for CMV and 50 to 100 times higher than in HI for rubella virus. PMID- 6265506 TI - Human rotavirus antigen detection by enzyme-immunoassay with antisera against Nebraska calf diarrhoea virus. AB - A four-layer solid phase enzyme-immunoassay (EIA) with antisera against Nebraska calf diarrhoea virus (NCDV) as immunoreagents was developed to detect human rotavirus antigens from stool specimens of patients with acute rotavirus gastroenteritis. Polystyrene beads were used as the solid phase, guinea-pig and rabbit anti-NCDV immunoglobulin as the catching and secondary antibody, and peroxidase-conjugated swine anti-rabbit immunoglobulin as the indicator antibody. A comparison of the developed NCDV-EIA with an identical EIA, using antisera against human rotavirus (HRV-EIA) instead of NCDV antisera, was made with 216 stool specimens positive or negative for rotavirus. A complete agreement was obtained between the two methods provided that appropriate confirmatory tests were included. The developed NCDV-EIA was as sensitive and specific for rotavirus as the HRV-EIA, and it allowed the detection of both established rotavirus types 1 and 2 from stools with equal sensitivity. The difficulties in cultivating human rotavirus in vitro for immunisation and the relative ease of growing NCDV in widely-used continuous cell lines make NCDV a good alternative in the preparation of the highly specific and sensitive rotavirus antisera required in immunoassays, and facilitate the setting-up methods for the routine diagnosis of rotavirus gastroenteritis by EIA or RIA in diagnostic virus laboratories. PMID- 6265505 TI - Occurrence of IgM antibodies against BK and JC polyomaviruses during pregnancy. AB - In a serological survey of 430 pregnant women 45 had high or rising titres of BK virus haemagglutination-inhibiting antibodies. The presence of BK-virus-specific IgM was confirmed in 10 of these women. No BK-virus-specific IgM was detected in the samples of cord blood from the babies born to these women. The sera from 40 women known to be excreting inclusion-bearing cells during pregnancy were tested for the presence of BK-virus and JC-virus-specific IgM and IgG. The presence of BK-virus-specific IgM was confirmed in three cases and JC-virus-specific IgM in seven cases. Specific IgM persisted for several months in some pregnant women. No Bk-virus-specific IgM was detected in any of the samples of cord blood from the babies born to these women with evidence of polyomavirus infection. No JC-virus specific IgM was detected in 36 out of 37 of the cord bloods; however, in one it is possible that minute amounts of JC-virus-specific IgM were present. PMID- 6265507 TI - Ultrastructure of the crayfish stretch receptor in relation to its function. AB - The crayfish slow-adapting abdominal stretch receptor was fixed under the relaxed or stretched condition. During this procedure action potentials of the sensory neuron were recorded by a suction electrode. The receptor organ consists of a receptor muscle and a sensory neurons with its dendrites embedded in the connective tissue zone in the receptor muscle. From the cell body of the neuron, several "primary dendrites" arise, branch successively into "dendritic branches", and finally terminate as "dendritic tips," which are cylindrical processes of fairly uniform diameter. In contrast to the primary dendrites and the dendritic branches, the dendritic tips have neither mitochondria nor sheaths and are embedded in the connective tissue zone or apposed to the receptor muscle with a gap of about 15 nm. Microtubules and smooth ER are seen in all parts of the dendrites. When the receptor is stretched and then fixed with 1.6% glutaraldehyde in 0.12 M phosphate buffer (total osmolarity of this solution is isosmotic with the physiological solution), dendritic tips became more parallel to the long axis of the receptor muscle and showed marked deformation consisting of alternate regions of swelling and shrinkage, resulting in a bead-like appearance. When fixed with 1.6% glutaraldehyde in 0.2 M phosphate buffer (total osmolarity of this solution is hyperosmotic), the dendritic tips showed less tendency toward such deformation. These results suggest that the dendritic tip membrane is susceptible to stretch and might be the region where the generator potential is produced. PMID- 6265508 TI - Thin-section and freeze-fracture studies of crayfish stretch receptor synapses including the reciprocal inhibitory synapse. AB - The crayfish slow-adapting abdominal stretch receptor organ is innervated by three inhibitory and several excitatory axons. A previous study by Tisdale and Nakajima ('76) showed that under certain fixation conditions inhibitory and excitatory synapses can be distinguished on the basis of synaptic vesicle structure. Using this morphological criterion we describe six types of synapses in the receptor: (1) the inhibitory axo-dendritic synapse, (2) the excitatory neuromuscular synapse, (3) the inhibitory neuromuscular synapse, (4) the axo axonic synapse which suggests presynaptic inhibition of the excitatory synapse, (5) the axo-axonic synapse which suggests presynaptic inhibition on the inhibitory synapse, (6) the reciprocal inhibitory axo-axonic synapse, which is a new type of synapse. The presence of these six types of synapse suggest that inhibitory and excitatory axons interact synaptically in a complicated manner, resulting in a delicate control of receptor function. In freeze fracture we have observed the presynaptic membrane structures of inhibitory and excitatory synapses. The active zone of the inhibitory synapse has ridges with loosely aggregated particles on the tops of the ridges and indentations (vesicle attachment sites) along their sides. The active zone of the excitatory neuromuscular synapse consists of bands of particle aggregates which are situated on slightly elevated membrane regions and surrounded by wide, relatively particle free, flat membrane areas. PMID- 6265509 TI - GABAergic synapses in the goldfish retina: an autoradiographic study of 3H muscimol and 3H-GABA binding. AB - The localization of synaptic receptor sites for gamma-amino butyric acid (GABA) in the goldfish retina was studied by light microscopic (LM) and electron microscopic autoradiography (EM-ARG) of 3H-muscimol and 3H-GABA binding. Sodium independent binding of both 3H-muscimol and 3H-GABA was localized to a uniform band throughout the inner plexiform layer (IPL) by LM-ARG of cryostat sections incubated in these compounds. No binding was observed over the outer plexiform layer. This binding pattern differs from the uptake pattern of 3H-GABA in the IPL, which shows very heavy labeling in the most proximal IPL and little labeling throughout the rest of the IPL. Statistical analysis of EM-ARGs of 3H-muscimol labeling in the IPL suggests that only amacrine synapses bind 3H-muscimol (i.e., make GABAergic synapses). Labeled amacrine-to-amacrine synapses are mostly concentrated in the 20-80% levels of the IPL, whereas amacrine-to-bipolar synapses are concentrated at about the 70-90% depth. Maximal 3H-GABA uptake, however, occurs at the 90-100% depth. This difference in the location of GABAergic synaptic binding and GABAergic uptake leads to the conclusion that the density of uptake label provides little information about the density of synaptic contacts. Thus, in order to localize GABAergic interactions, synaptic binding rather than neuronal uptake appears to provide the more appropriate description. PMID- 6265510 TI - Inhibition by ADP of prostaglandin induced accumulation of cyclic AMP in intact human platelets. AB - The influence of extracellular ADP on cyclic AMP accumulation within intact human platelets was studied. ADP inhibited the increase in cyclic AMP which occurs when platelets are exposed to prostaglandin E1 or I2. The degree of inhibition varied in the range 70-95% , and was half maximal at ADP concentrations of between 0.3 and 2 microM. Other naturally occurring diphosphates, i.e. GDP, IDP and UDP, were at least 100 fold less effective than ADP, and UDP at 1mM partially reversed the effect of ADP. The effect by ADP was completely reversed by ATP, but only attenuated to a minor degree of 10 mM EDTA. Increasing concentrations of ADP caused a progressive degree of inhibition of cyclic AMP accumulation, and the kinetics of this inhibition were compatible with a simple saturable process with no cooperativity. ADP added 10 seconds after prostaglandin E1 blocked cyclic AMP accumulation within 1-2 seconds, and addition of ATP after ADP and prostaglandin I2 relieved the inhibition due to ADP within 2-3 seconds. The action of ADP was blocked by sulphydryl reagents including N-substituted maleimides, cytochalasin A, NBD chloride and p-mercuribenzene sulphonate. The data were considered to be consistent with mediation of the ADP effect through a sulphydryl-bearing specific extracellular receptor coupled to the adenylate cyclase. PMID- 6265511 TI - [125I]iodopindolol: a new beta adrenergic receptor probe. AB - When utilizing iodohydroxybenzylpindolol (IHYP) as an adrenergic receptor probe in muscle membrane systems, the data demonstrated an unacceptably high nonspecific binding component. Bearer et al. have reported that chloramine-T induced iodination of hydroxybenzylpindolol (HYP) results in the incorporation of iodine into the indole ring rather than into the phenolic moiety as noted previously by others. These results suggest that pindolol itself can also be iodinated. Therefore, the usefulness of carrier free 125I-labeled iodopindolol (IPIN) as an adrenergic receptor probe was investigated. Using between 0.01 nM and 0.1 nM [125I]IPIN in two different muscle membrane systems, we found the nonspecific binding component to be 10% or less of total binding. When [125I]IPIN was used with membranes prepared from rat skeletal muscle, we found it to interact with a single set of high affinity binding sites (KD = 0.13 +/- 0.01 nM) with the characteristics of beta adrenergic receptors and a density of 48.5 fmoles/mg protein. IPIN binding was also studied with purified dog cardiac sarcolemma. A single set of binding sites was detected having a KD of 1.64 +/- 0.5 nM; the density of these sites was 289 fmoles/mg membrane protein. [125I]IPIN may be a useful probe for the beta adrenergic receptor of tissues in which [125I]IHYP and other beta adrenergic receptor probes have a non-specific binding component which approaches that of the specific binding component. PMID- 6265512 TI - A simple fluorometric method for cAMP: application to studies of brain adenylate cyclase activity. AB - A simple fluorometric method for the determination of cAMP is presented. The fluorescent derivative is 1,N6-etheno cyclic 3,5-monophosphate (etheno-cAMP). Maximal formation of this derivative occurs after reacting cAMP with chloroacetaldehyde for 15 minutes at 100 degrees C. Fluorescent derivatives are also produced from compounds which contain a 6-amino purine. The specificity of the method resides in the use of a reverse phase/HPLC system. The derivatization as well as the fluorescent response of etheno-cAMP is linear between 2.5 and 700 picomoles of cAMP. Studies of brain adenylate cyclase by the fluorometric/HPLC method indicated that this method is comparable to the established radioenzymatic method. Thus, the present method provides a simple rapid nonradioactive means for the determination of adenylate cyclase activity. PMID- 6265513 TI - Catecholamine-induced desensitization in turkey erythrocytes: cAMP mediated impairment of high affinity agonist binding without alteration in receptor number. AB - Desensitization of turkey erythrocyte adenylate cyclase by exposure of these cells to the beta-adrenergic agonist isoproterenol leads to a decrease in subsequent adenylate cyclase stimulation by isoproterenol, F-, or Gpp(NH)p without any apparent loss or down regulation of receptors (B.B. Hoffman et al. J. Cyclic Nucl. Res. 5: 363-366, 1979). We now report that the desensitization is associated with a functional "uncoupling" of the beta-adrenergic receptor. This is evidenced by an impaired ability of receptors to form a high affinity, guanine nucleotide sensitive complex with agonist as assessed by computer analysis of radioligand binding data. The changes in adenylate cyclase responsiveness as well as the alterations in receptor affinity for agonists are reproduced by incubation of turkey erythrocytes with the cAMP analog 8-Bromo-adenosine 3':5'- cyclic monophosphate. These findings suggest that one possible mechanism for the development of desensitization in adenylate cyclase systems may be a cAMP mediated alteration of a component(s) of the beta-adrenergic receptor-adenylate cyclase complex which results in impaired receptor-cyclase coupling. PMID- 6265514 TI - Decomposition of gypsum bonded investments. AB - Decomposition of gypsum bonded investments was investigated by means of TG-DTA and X-ray diffraction. The decomposition began at about 900 degrees C and led to the formation of CaSiO3 as a major product and Ca2SiO4 as a minor one. CaO was not formed during the decomposition of any of the investments. The decomposition process followed Jander's equation, [1-(1-alpha)1/3]2 = kt, and the Ca2+ ion diffusion in CaSiO3 was concluded to be a rate-determining step. PMID- 6265515 TI - Current concepts of the mechanism of action of local anesthetics. AB - Recent experiments are reviewed to present a current view of the mechanisms of conduction block by local anesthetics. Local anesthetics block the sodium channels whose opening causes the rising phase of the action potential. Both charged and neutral forms of local anesthetics are able to block channels. Charged anesthetics interfere with a "gating" mechanism after gaining access to a "receptor" site in the aqueous pore of the channel from the axoplasmic surface of the membrane. This site is only available to charged compounds when the gate of the channel is open. In contrast, uncharged compounds (including the free base form of local anesthetics) appear to reach the site through the membrane's lipid interior, bypassing the channel "gates." Anesthetics blocking the gate of the channel can either enhance or inhibit the normal inactivation mechanism of the sodium channel, depending on the particular anesthetic. PMID- 6265516 TI - [Hydrogen and hydroxyl ion regulation of the fatty acid makeup of Cl. perfringens type A cells]. PMID- 6265517 TI - Chemical properties and interactions of rice hemicellulose with trace minerals in vitro. PMID- 6265518 TI - Molecular interactions with dietary fiber components. Investigation of the possible association of pectin and bile acids. PMID- 6265519 TI - Nutrient utilization by human subjects consuming fruits and vegetables as sources of fiber. PMID- 6265520 TI - Nutritional significance of dietary fiber: effect on nutrient bioavailability and selected gastrointestinal functions. PMID- 6265522 TI - Prevalence of herpes simplex virus disease in a professional population. AB - By virtue of occupation, dentists are frequently exposed to the herpes simplex virus. The risk of infection by the virus was evaluated by assessing disease experience as shown by history compared with the results of complement fixing or antibody titration tests, or both. PMID- 6265524 TI - Surgical oncology: current emphasis and approach. PMID- 6265523 TI - Asymptomatic, nonulcerated swelling of the palate. PMID- 6265521 TI - Enzymatic degradation of the plant cell wall by a Bacteroides of human fecal origin. PMID- 6265525 TI - Social support groups, women's programs, and research on gender differences: the bad press for women in medical education literature. PMID- 6265526 TI - Series on endocrine metabolic emergencies: L. Hyperosmolar hyperglycemic nonketotic coma. PMID- 6265527 TI - Interesting nuclear medicine and computed tomography (CT) scans. PMID- 6265528 TI - Women physicians chairing pediatric departments in American medical schools, 1980. PMID- 6265529 TI - Colitis cystica profunda. PMID- 6265530 TI - Series on endocrine metabolic emergencies: II. Acute adrenal insufficiency. PMID- 6265531 TI - Children and divorce: a review of real world factors. PMID- 6265532 TI - The achievement of men and women in medical school. PMID- 6265533 TI - Series on endocrine metabolic emergencies: III. Myxedema coma. PMID- 6265534 TI - Children during residency: it's easier if you're a man. PMID- 6265535 TI - Childhood sexual abuse: a recent review of the literature. PMID- 6265536 TI - Monitoring volume changes in red cell ghosts by means of a trapped fluorescent probe. AB - A method is described for monitoring changes in the volume of red cell ghosts by means of a fluorescent probe trapped inside them.. The fluorophore, 8-hydroxy 1,3,6-pyrenetrisulfonate, is partially quenched by the residual hemoglobin in the ghosts. When the ghosts swell, the hemoglobin concentration is reduced, the quenching is somewhat relieved and the fluorescence output increases. Opposite changes occur when the ghosts shrink. Fluorescence intensity is linearly related to ghost volume for both swelling and shrinking, but there is a larger change in fluorescence for shrinking from the isotonic volume than for an equivalent swelling. This method has been used to follow the swelling phase of dye-loaded ghosts suspended in a solution of a penetrating nonelectrolyte in isotonic saline. PMID- 6265537 TI - Responses of single units in the inferior olive nucleus to stimulation of the splanchnic afferents in the cat. AB - The activity of olivary neurons in the caudal parts of the medial accessory olive (MAO) and dorsal accessory olive (DAO) was recorded with extracellular microelectrodes in anesthetized cats. The responses were obtained by electrical stimulation of the contralateral splanchnic nerve and mechanical stimulations of gastro-intestinal and peritoneal receptors. The stimulated mechanoreceptors were slowly adapting muscular receptors of the stomach (connected with C fibers) and slowly adapting peritoneal movement receptors (connected with A gamma delta or B fibers). Splanchno-visceral, splanchno-somatic and splanchno-cortical convergences were observed, as in the cerebellum (lobule V and VI). So, the inferior olive must be considered as an integrating structure not only for central and somatic messages, but also for visceral ones. PMID- 6265538 TI - Dihydroergocryptine binding sites in bovine and rat pineal glands. AB - High affinity binding of [3H]dihydroergocryptine (DHE) to crude membrane preparations of bovine and rat pineal glands was examined by a rapid filtration procedure through Whatman GFB paper. Scatchard analysis of bovine pineal membranes revealed a single population of binding sites with Kd = (4.8 +/- 1.9) X 10(-8) M (mean +/- S.E.M., n = 3) and binding site concentration = 834 +/- 103 fmol/mg of protein. When various alpha- and beta-adrenergic agonists or antagonists were tested for their ability to inhibit [3H]DHE binding the following Ki values (microM) were obtained: DHE (0.039), phentolamine (0.102), phenoxybenzamine (0.262), methysergide (0.670), L-epinephrine (2.27), serotonin (3.09), L-norepinephrine (3.20), octopamine (30.3), L-propranolol (1710), L isoproterenol (greater than 2000). In order to obtain information on the pre- or postsynaptic location of pineal DHE binding sites, pineal 900 g supernatants were prepared from rats subjected to bilateral superior cervical ganglionectomy or sham-operation 7 days earlier. Ganglionectomy caused a 53% increase in the number of binding sites without changing significantly their Kd (5.2 X 10(-8) M and 5.5 X 10(-8) M in ganglionectomized and control rats, respectively). These results are compatible with the view that postsynaptic alpha-adrenoceptors are present in the pineal gland. PMID- 6265539 TI - Effects of pesticides on activities of enzymes and microorganisms in a clay soil. AB - Laboratory experiments were conducted to determine the effect of 32 pesticides applied at 2 levels on populations of microorganisms, activities of urease, dehydrogenase, phosphatase and nitrogenase in a clay loam incubated for 1 week. Results indicated that a decrease in bacterial number was observed with thiram for 2 days and stimulation with chlorpyrifos after 7 days. Some fungicides and fumigants inhibited fungal numbers for 2 days. The recovery was rapid and stimulatory effects on microbial numbers were evident in many samples. None of the pesticides inhibited soil urease drastically. Formazan formation was not suppressed vigorously by the treatments. With the exception of DD and Vorlex at a high level, none of the treatments inhibited phosphatase in the hydrolysis of p nitrophenyl disodium orthophosphate. A temporary decrease in nitrogenase activity in acetylene (C2H2) reduction was observed with many pesticides. The low amount of pesticides applied to the clay loam is unlikely to have detrimental effects on soil microbes and the enzymes important to soil fertility. PMID- 6265540 TI - Effects of periodontal stimulation on the masseteric gamma motor fiber. PMID- 6265542 TI - Intraosseous glomus tumor--case report. AB - This case of an intraosseous glomus tumor reported in a 42-year-old Chinese housewife is believed to be the tenth case in medical literature. It was discovered on review of bone biopsy material examined at the Department of Pathology, Queen Mary Hospital, Hong Kong. PMID- 6265541 TI - Phosphotransferases and lysosomal enzymes in fetal human and rat lung. AB - The present investigations on rat lung show that metabolic changes occurring around the 20th gestational day are accompanied by multiple alterations in the quantitative pattern of enzymes. This involves increases in two lysosomal enzymes (N-acetyl beta-glucosaminidase and beta-galactosidase) and a rise and fall in pyruvate kinase and alpha-glucosidase. The striking transient upsurge of adenylate kinase, however, is postponed until after birth. The normal diminution of thymidine kinase and peptidylproline hydroxylase is drastically enhanced by an injection of cortisol to fetal rats. Studies on human pulmonary tissues consisted in determining enzyme concentration from the ninth to the 21st week of gestation and an histologically normal adult lungs. The results show that the 15th to the 21st week of gestation is the period of increase in pyruvate kinase, adenylate kinase and alpha-glucosidase. The rise during the development of several enzymes (e.g., 5'-nucleotidase, alkaline phosphatase, and gamma-glutamyl transpeptidase) and the decline in thymidine kinase and peptidylproline hydroxylase, however, dose not begin until after the 21st week of gestation. PMID- 6265543 TI - Cationic ferritin binding sites and surface charge densities of transformed cells. AB - Bioelectric surface properties of the high and low tumor-producing cell lines, NCTC 2472 and NCTC 2555, respectively, were determined by cationic ferritin binding and the electrophoretic mobility of intact cells. Measurements of anionic sites were bases on the number of cationic ferritin particles per 0.01 mu 2 that were electronically tagged and counted by an image analyzer. The average particle count was 45 for the control "high" cells and 34 for the control "low" cells. The surface charge densities, expressed as electrostatic units per cm-2 x 10(-13) were 2.34 and 1.18 at 50 V (2 mA) for the "high" and "low" control cells, respectively. Enzymic cleavage of sialic acid and other carbohydrate moieties resulted in up to an 81% reduction in the charge densities and a 57% reduction of the anionic sites of the "high" cells. The electrophoretic mobility of cells with bound cationic ferritin showed that up to 50% of the exposed anionic sites fail to bind cationic ferritin. Preliminary findings on the particle size/distribution by image analysis showed wide ranges in both particle size and interparticle distances that may limit cationic ferritin binding. PMID- 6265544 TI - Conjugation of horseradish peroxidase to staphylococcal protein A with benzoquinone, glutaraldehyde, or periodate as cross-linking reagents. AB - Horseradish peroxidase was conjugated to Staphylococcal protein A by three different two-step procedures using an increasing excess of peroxidase in the second step reaction. The yield of conjugated protein A was analyzed by SDS polyacrylamide gel electrophoresis. Conjugation of peroxidase to protein A with benzoquinone or glutaraldehyde as cross-linking reagents at a 3- to 4-fold molar excess of peroxidase resulted in a high yield of coupled protein A with conjugates of low molecular size. Conjugation of peroxidase to protein A by the periodate method resulted in a high yield of coupled protein A with polymeric conjugates of large molecular size. Based on these results, conjugates produced with glutaraldehyde as cross-linking reagents were further analyzed. The capacity of the conjugates to precipitate human immunoglobulin evaluated by radial immunodiffusion was found to be reduced to about 50% of that of native protein A. Conjugates produced with glutaraldehyde as cross-linking reagent retained 70% of the enzyme activity of native peroxidase. PMID- 6265545 TI - Cytochemical localization of glucose-6-phosphatase in rabbit mononuclear phagocytes during differentiation. AB - Cytochemical and biochemical investigations have revealed glucose-6-phosphatase (G-6-Pase) activity in Kupffer cells of the liver. To determine whether other mononuclear phagocytes are also reactive for G-6-Pase, rabbit bone marrow, blood, and alveolar macrophages were tested for G-6-Pase by a modified Wachstein-Meisel method and prepared for electron microscopy. Some mononuclear phagocytes from all three tissues were intensely reactive; others were unreactive. In promonocytes, monocytes, and alveolar macrophages, reaction product for the enzyme was localized throughout all cisternae of the endoplasmic reticulum (ER) and the perinuclear cisternae, but it was absent from the Golgi complex, lysosomes, and occasional smooth tubular channels. These results indicate that mononuclear phagocytes at all stages of development contain cytochemically demonstrable G-6 Pase and that the distribution of the enzyme is not altered during their differentiation from immature cells in the bone marrow to mature macrophages in the lung. PMID- 6265546 TI - Ultrastructural localization of nuclei acids by the use of enzyme-gold complexes. AB - A cytochemical technique for the ultrastructural localization of substrates using enzyme-gold complexes is reported. RNase A and DNase I have been labeled with gold particles. The RNase-gold and dNase-gold complexes obtained were applied on thin sections of glutaraldehyde-fixed and Epon-embedded tissues. Different cellular compartments were labeled by these enzyme-gold complexes. Using the RNase-gold complex the rough endoplasmic reticulum appeared decorated with gold particles. The gold marker was also present over the nucleus, especially over the nucleolus; mitochondria were weakly labeled. Using the DNase-gold complex, gold particles were concentrated over the euchromatin of the nucleus and the mitochondria. The heterochromatin and the nucleolus showed a less intense labeling. For both enzyme-gold complexes, the Golgi area, the secretory granules and the extracellular space appeared free of label. In those control conditions where the substrates were added to the enzyme-gold complexes a major reduction in the labeling was observed. A quantitative evaluation of the labeling was performed. This evaluation confirmed the qualitative observations and the marked reduction of labeling occurring under the control conditions. The combination of the specificity of the enzyme-substrate interactions with the size and electron density of the gold particles and the good ultrastructural preservation of the tissues resulted in a very specific labeling with high resolution. These results demonstrate the possibility of detecting substrates by means of enzyme-gold complexes at the electron microscope level. PMID- 6265547 TI - Evaluation of periodate/lysine/paraformaldehyde fixation as a method for cross linking plasma membrane glycoproteins. AB - Fixation by periodate/lysine/paraformaldehyde, a method purported to cross-link specifically plasma membrane glycoproteins, was evaluated using Novikoff rat ascites hepatocellular carcinoma cells. Cells were treated with periodate/lysine, periodate/glycine, and periodate/lysine/paraformaldehyde and subsequently reduced with NaB3H4. The glycoproteins labeled with 3H were resolved by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and visualized by fluorography. The effects of reactant concentrations on 3H-labeling of cellular components, cell viability, and cross-linkage of 3H-labeled proteins were examined. The effect of increasing the localized density of plasma membrane glycoproteins on the extent of cross-linkage by periodate and lysine was investigated using cells in which patching of the plasma membrane glycoproteins had been induced by ferritin-conjugated concanavalin A/rabbit antiferritin antiserum. Also investigated was the periodate-independent to mixtures of periodate and lysine or glycine. Results of these studies did not support a mechanism of cross-linking involving reaction between the free base lysin and aldehyde groups on periodate oxidized carbohydrate residues but suggested a complex interaction between periodate oxidized plasma membrane glycoproteins and polymeric complexes of lysine and formaldehyde.U PMID- 6265548 TI - The effect of epidermal growth factor (EGF) on the differentiation of the rough endoplasmic reticulum in fetal mouse small intestine in organ culture. AB - The differentiation of the rough endoplasmic reticulum (RER) of mouse duodenal absorptive cells located at the tip of the villi at 17 days of gestation was compared to that of absorptive cells in duodenal explants of 15-day-old mouse fetuses cultured for 72 hr 1) with Trowell T8 medium (without insulin) alone or supplemented 2) with epidermal growth factor (EGF; 100 ng/ml) or 3) with 25% bovine amniotic fluid (BAF). Glucose-6-phosphatase activity (G6Pase) was localized cytochemically to ensure a better identification of the RER. The intersections of a double lattice falling over and outside the RER were counted and the percentage of intersections over the RER was estimated. With this method, the extent of the RER is not statistically different when the absorptive cells in utero are compared to those of explants cultured with EGF. However, the extent of the RER in the absorptive cells cultured with Trowell T8 medium alone or supplemented with BAF is 50% lower than in the former two groups. It is concluded that EGF promotes the maturation of duodenal absorptive cells in organ culture. PMID- 6265549 TI - Potential use of attenuated langat E5 virus as a live vaccine -- long term protection against Russian spring-summer encephalitis virus in mice. AB - A single inoculation of Langat E5 virus provides 90-100% protection in mice against 3200-16000 lethal doses of Russian Spring-Summer Encephalitis (RSSE) virus when challenged 18 or 24 months later. The observed protection is found in the absence of neutralizing antibody (NA) against RSSE virus at the time of challenge but is associated with anamnestic NA response. Immunized mice have low titer short duration viremia. Immunized mice have late first detection and much lower multiplication in the brains, even though traces of virus could be detected in the brain up to 3 weeks following challenge. The observed protection results from sensitization due to immunization and quick host response following RSSE challenge resulting in significantly altered viral pathogenesis. Long term cross protection studies reported in this study and before coupled with the experience of the use of attenuated Langat E5 virus in humans volunteers suggests to its further testing as a live vaccine for prophylaxis against various members of Russian Spring-Summer virus complex throughout the world. PMID- 6265550 TI - Survival of polioviruses and echoviruses in Acanthamoeba castellanii cultivated in vitro. AB - Cultures of Acanthamoeba castellanii, kept at room temperature in sterile Bacto Casitone (Difco) medium, were artificially infected with vaccination poliovirus strains type 1 and type 3 and with echovirus type 4 and echovirus type 30. No remarkable virus cumulation was observed on the surface or inside amoeba cells during the observation period of 21 days. Amoeba-adsorbed viruses were impossible to remove by repeated washings. Virus neutralization with specific antisera showed that enteroviruses were most probably present only on amoeba surfaces. In contrast to amoeba-free virus suspension, echoviruses bound to amoebae and their cell pulp persisted even after 52 to 75 days. However, the tested amoeba species played only the role of a solids-like carrier in this survival of echoviruses. PMID- 6265551 TI - Immune responsiveness of HRS/J mice to syngeneic lymphoma cells. AB - HRS/J, hr/hr and hr/+ mice were evaluated for their ability to resist challenge with a syngeneic tumor, HTU, and for their ability to mount a protective immune response when immunized in vivo with inactivated HTU cells previous to challenge with viable tumors. The heterozygous (hr/+) mice responded more strongly than the homozygous (hr/hr) mice. This response was characterized by the presence of an enhanced ability of spleen cells from immunized mice to form blasts in vitro when incubated with purified murine leukemia viruses (MuLV). We conclude that the in vivo response of HRS/J mice against this tumor is directed, in part, against MuLV antigens expressed on the tumor cells and that the relatively weak response of hr/hr spleen cells to these antigens may be mechanistically linked to their tumor susceptibility. PMID- 6265552 TI - Effect of physical stress on sensitivity of lymphocytes to inhibition by prostaglandin E2. AB - Physical stress is associated with depressed cellular immune function. We have found that lymphocytes from subjects undergoing either of 2 stressful events, cardiac surgery or childbirth, are more sensitive to inhibition by PGE2. For example, the concentration of PGE2 required for 50% inhibition of 3H-thymidine incorporation (ID50) into phytohemagglutinin-stimulated lymphocytes from patients undergoing cardiac surgery went from 1.5 X 10(-8) M on the day before surgery to 3 X 10(-9) M on the day after surgery. This increase in sensitivity to PGE2 was accompanied by a significantly decreased lymphocyte proliferative response (27 to 68% of control, depending on mitogen dose) and a 50% increase in the percentage of E rosette-positive cells with receptors for the Fc portion of IgG. The increased sensitivity to PGE and the depressed mitogen responses returned to preoperative values by day 10. The depressed mitogen responses of the postoperative patients were completely restored to normal by removal of glass adherent cells before culture. In addition, the responses of the postoperative patients and the women in labor were partially restored by the addition of indomethacin, a prostaglandin synthetase inhibitor, to the cultures. Thus it would appear that physical stress causes lymphocytes to become more sensitive to prostaglandin E2, and the increased sensitivity to inhibition by this immunomodulator is responsible in part for the depressed cellular immune function after physical stress. PMID- 6265553 TI - Discordant expression of 2 Epstein-Barr virus-associated antigens, EBNA and RANA, in man-rodent somatic cell hybrids. AB - The Epstein Barr nuclear antigen (EBNA) and the rheumatoid arthritis nuclear antigen (RANA) develop in human B lymphocytes that have been infected and transformed by Epstein Barr virus (EBV). Antibodies to RANA and EBNA are found only in individuals with prior exposure to EBV. The purpose of the present studies was to determine the relation of the 2 antigens to each other and to EBV genetic material, in human-rodent somatic cell hybrids. Cultured human B lymphoblastoid cells, Raji, Daudi, and RPMI 4098 were fused with thymidine kinase deficient mouse or hamster fibroblasts. After selection and cloning in ouabain HAT medium, the hybrid nature of the surviving cells was confirmed by isozyme analysis. The hybrid clones were analyzed for EBNA by anti-complement im,munofluorescence, and for RANA by anti-immunoglobulin immunofluorescence and immunodiffusion. The results showed that RANA and EBNA segregated entirely independently of each other in the hybrid clones. Two methods were used to detect the presence of EBV DNA sequences in the intracellular DNA of hybrid clones. The 1st method relied on the hybridization of labeled cRNA prepared from virion DNA with DNA from 8 hybrid clones affixed to nitrocellulose filters. The 2nd approach was to hybridize labeled intracellular DNA from 3 hybrid clones to Southern blots of cloned fragments of EBV DNA. These results suggested that the presence of EBV DNA was not sufficient for the expression of either antigen. One stable RANA positive hybrid cell line contained at least 80% of the EBV genome in the absence of detectable EBNA. PMID- 6265554 TI - Studies of the physical biochemistry and complement-fixing properties of DNA/anti DNA immune complexes. PMID- 6265555 TI - A murine stage-specific embryonic antigen (SSEA-2) is expressed on some murine SV40-transformed cells. AB - A stage-specific embryonic antigen-2 (SSEA-2) found on murine preimplantation embryos is maximally expressed on 4- to 8-cell stage embryos and is present in decreasing amounts of morulae and blastocysts. This antigenic determinant is also expressed on murine teratocarcinoma cells, sperm, and some, but not all, SV40 transformed mouse cell lines. Analysis of solubilized immunoprecipitates by SDS gel electrophoresis indicates that this cell surface molecule is not the 54,000 m.w. protein shared by teratocarcinoma and SV40-transformed cell lines. PMID- 6265556 TI - Formate oxidation as a measure of hydrogen peroxide production: effect of pH and involvement of superoxide anion. PMID- 6265557 TI - T lymphocyte-mediated cytolysis. II. Role of target cell histocompatibility antigens in recognition and lysis. AB - Although compelling genetic and serologic evidence implicate target cell (TC) MHC antigens in specific cytotoxic T lymphocyte (CTL)-TC interaction leading to lysis, it is not entirely clear whether TC recognition through an MHC determinant(s) is a prerequisite for lysis to occur. In fact the finding that both specific and nonspecific TC are lysed equally well in lectin-dependent cell mediated cytotoxicity (LDCC) challenges the necessity for TC MHC involvement in the cytolytic process beyond providing the basis for specificity in direct (nonlectin-dependent) CTL-mediated lysis. In the present paper we present evidence suggesting that even in nonspecific LDCC, as well as in nonspecific lymphocyte-mediated lysis of TC oxidized by periodate treatment or by galactose oxidase (ODCC), TC MHC components are required for lytic interactions with cytotoxic effector cells. This conclusion is based on 3 types of experimental evidence: 1) cells displaying reduced amounts of MHC proteins are poor targets in LDCC; 2) removal of H-2 by papain renders murine target cells refractory to lysis in LDCC, even though Con A binding is only slightly reduced; 3) antisera to target cell H-2-coded products block lysis in both LDCC and ODCC, whereas antisera to other cell surface antigens do not. A theory explaining nonspecific effector target interaction leading to lysis based on involvement of CTL receptor(s) and TC MHC components is presented. PMID- 6265558 TI - Stimulation of immunoglobulin biosynthesis in human B cells by wheat germ agglutinin. I. Evidence that WGA can produce both a positive and negative signal for activation of human lymphocytes. AB - Wheat germ agglutinin (WGA), previously regarded strictly as a nonmitogenic or anti-mitogenic lectin, can under appropriate conditions markedly stimulate in vitro synthesis and secretion of immunoglobulin (Ig) by human B lymphocytes. Stimulation of Ig production by WGA is 1) confined to a narrow lectin dose range (2 to 10 micrograms/ml; 2) abrogated by the simple sugar N-acetyl-D-glucosamine but not by a variety of other monosaccharides; 3) effective only after early additions of WGA within the initial 72 hr of 12-day cultures; 4) detected in the presence of B and T cells but not B cells alone; and 5) polyisotypic in nature, as indicated by augmented synthetic rates of Ig in each of 3 major classes (IgG, IgA, and IgM). With few exceptions, WGA produces equivalent or greater rates of Ig production as obtained in cultures activated with pokeweed mitogen (PWM), a well-recognized T-dependent polyclonal activator of human B cells. Furthermore, periperal blood lymphocytes from select individuals that respond weakly to PWM are markedly stimulated with WGA. In contrast to these stimulatory effects of WGA on Ig production by lymphocytes exposed to low lectin concentrations, addition of WGA in amounts greater than 15 micrograms/ml to PWM-stimulated human lymphocyte cultures produces marked suppression of the expected level of Ig synthesis. These data indicate that varying doses of WGA can produce contrasting stimulatory and inhibitory effects on human B cell metabolism. PMID- 6265559 TI - Preparation of protein A-peroxidase monoconjugate using a heterobifunctional reagent, and its use in enzyme immunoassays. AB - Protein A-peroxidase monoconjugate was prepared in solution using a heterobifunctional reagent, N-succinimidyl-3-(2-pyridyldithio)-propionate. The yield of the monoconjugate was much higher than that obtained with current methods. An immunoassay method was developed in which protein A-peroxidase monoconjugate served as a universal tool. Protein A-peroxidase monoconjugate was taken up by IgG molecules immobilized on an excess of solid phase antigen. The ability of free antigen to inhibit the binding of antibody, measured as inhibition of conjugate up take, served as the basis for quantification in the assay. The method was applied to human chorionic gonadotropin (HCG) and human IgG. Optimal assay conditions were developed and it was found that as little as 1 ng of HCG/ml and 2 ng of IgG/ml could be detected. The method is of comparable sensitivity to other available immunoassay methods and gives accurate, reproducible results. PMID- 6265561 TI - Production of monospecific antibodies to varicella zoster virus antigen in rabbits tolerant to human IgG and immunized with antigen immunoprecipitated with human IgG from zoster reconvalescent sera. AB - A method for production of antisera specific to a single antigen of a human infectious agent is described with varicella zoster virus (VZV) as a model. Microisolation of immunochemically pure antigen contained in defined immunoprecipitates was achieved by crossed immunoelectrophoresis of a crude antigenic preparation (detergent solubilized, VZV infected cells) into agarose gel containing zoster reconvalescent immunoglobulin. Immunization of rabbits made tolerant to human IgG with immunoprecipitates resulted in the production of antibodies to the antigen part of the immunoprecipitate. The method represents a short cut to the production of heterologous diagnostic antisera to defined antigens of human infectious agents. PMID- 6265560 TI - Antisera to late cytomegalovirus nuclear antigens produced in cynomolgus monkeys. PMID- 6265562 TI - Development of an anticomplement immunoenzyme test for detection of EB virus nuclear antigen (EBNA) and antibody to EBNA. AB - An anticomplement immunoenzyme test was developed by conjugating anti-human C3 antibody with horseradish peroxidase. EBNA could be detected by this test in all cell lines related to EB virus, as well as in nasopharyngeal carcinoma cells, but not in unrelated cell lines. Antibody to EBNA could also be detected. The test is sensitive and does not require a fluorescence microscope which makes it particularly suitable for mass survey. PMID- 6265563 TI - Alterations of immune reactivity by haloperidol and delta-9-tetrahydrocannabinol. AB - Studies were performed to determine whether delta 9-tetrahydrocannabinol (THC) or haloperidol suppress or ablate humoral or cellular immune responses against sheep erythrocytes. Both agents produced dose-dependent reductions in hemolytic plaque forming cell (PFC) numbers at the time or peak reactivity (Day 4) in vehicle treated, control mice. However, both delta 9-THC and haloperidol only delayed the time of peak PFC formation by 24-48 hours. These changes in kinetics of humoral immune responsiveness took place at doses of delta 9-THC and haloperidol that produced signs of gross behavioral toxicity. Neither Delta-9-THC, cannabinol (CBN) or cannabidiol (CBD) had an effect on the titer of serum hemagglutinating antibody measured seven days after immunization. Further, haloperidol did not alter the delayed-type hypersensitivity response to dinitroflorobenzene (DNFB). PMID- 6265564 TI - The cutaneous photosynthesis of previtamin D3: a unique photoendocrine system. AB - The skin has been recognized as the site for the sun-mediated photosynthesis of vitamin D3; until recently, however, very little was known about either the sequence of events leading to the formation of vitamin D3 in human skin or the factors that regulate the synthesis of this hormone. It is now established that, during exposure to sunlight, the cutaneous reservoir of 7-dehydrocholesterol (principally in the stratum Malpighii) converts to previtamin D3. Once this thermally labile previtamin is formed, it undergoes a temperature-dependent isomerization to vitamin D3 over a period of 3 days. The plasma vitamin-D binding protein preferentially translocates vitamin D3 from the skin into the circulation. During prolonged exposure to the sun, the accumulation of previtamin D3 is limited to about 10 to 15% of the original 7-dehydrocholesterol content because the previtamin photoisomerizes to 2 biologically inert photoproducts, lumisterol3 and tachysterol3. Increases in either latitude or the melanin concentration in the skin diminish the epidermal synthesis of previtamin D3. A single total body exposure to 3 minimal erythemal doses of ultraviolet radiation increased the vitamin-D3 levels in the serum 25-hydroxyvitamin-D levels after 7 days. The unique mechanism for the cutaneous synthesis, storage, and steady release of vitamin D3 into the circulation prompted an investigation into the potential therapeutic benefits of using the skin as the site for the synthesis and absorption of vitamin-D3 metabolites. PMID- 6265565 TI - A 27-nm virus isolated during an outbreak of acute infectious nonbacterial gastroenteritis in a convalescent hospital: a possible new serotype. AB - An outbreak of acute infectious nonbacterial gastroenteritis began among elderly patients in a convalescent hospital in Marin County in northern California in March 1978 and persisted through May 1978. The overall clinical attack rate was 51% of 187 residents and 12% of 180 employees. A 27-nm viruslike particle was observed by immune electron microscopy in stools obtained at or near the onset of illness from four of 32 patients. Seroresponses to the 27-nm particles were found by immune electron microscopy in 16 of 18 patients. In addition, serologic evidence of infection with this or a related agent was demonstrated in persons who developed illness in another large outbreak of acute infectious nonbacterial gastroenteritis which occurred in a nearby county. This agent is morphologically similar to but serologically unrelated to the Norwalk and Hawaii gastroenteritis agents and has been designated the Marin agent pending further classification. PMID- 6265566 TI - Cytolytic IgM antibody to cytomegalovirus in primary cytomegalovirus infection in humans. AB - Suspensions of cytomegalovirus (CMV)-infected human foreskin fibroblasts were used to measure cytolytic antibody (CyA) to CMV in serum by a 51Cr release assay. CyA was associated with IgM but not with IgG antibody to CMV, required rabbit or human complement, and was directed at a surface antigen. CyA was detectable for one to three months in the sera of 16 patients with community-acquired CMV infection and in the sera of 20 of 22 renal transplant recipients with primary CMV infection. CyA was found less frequently in the sera of renal transplant recipients with reactivated CMV infection and occurred almost exclusively when the donor was seropositive for CMV. One individual, unlike many patients with CyA, was free of symptoms. Sera from patients with either rheumatoid factor positive arthritis or heterophil-positive infectious mononucleosis and from 70 of 71 control patients with other types of antibody to CMV yielded no 51Cr release. PMID- 6265567 TI - The lymphocyte in infections with Epstein-Barr virus and cytomegalovirus. PMID- 6265568 TI - [Transforming genes present in avian sarcoma viruses: src gene and newly discovered genes and their gene products (author's transl)]. PMID- 6265569 TI - Trophoblastic disease: a five year experience. PMID- 6265570 TI - Cholesterol and atheroma lipids activate complement and stimulate granulocytes. A possible mechanism for amplification of ischemic injury in atherosclerotic states. AB - Previous studies in experimental myocardial infarction have suggested that PMNs and plasma C might interact to intensify ischemic injury. From the finding of large amounts of activated C (specifically C5a) in the plasma of a patient with severe, ulcerating atherosclerosis and the cholesterol embolization syndrome, we postulated that crystalline cholesterol might activate C and thereby amplify infarctive tissue damage. On simple incubation, crystalline cholesterol--as well as lipids from atheromata--activated plasma C; such plasma then potently aggregated normal PMNs and provoked them to damage cultured endothelial cells in vitro. The active principle in cholesterol-incubated plasma was of molecular weight and antigenicity consistent with C5a (or C5a[desarginine]). Optimal activation required the presence of Ig and an intact classical C pathway. Exposure of plasma to crystalline cholesterol by ulceration of, or hemorrhage into, atherosclerotic plaques might therefore activate C in vivo, promoting further ischemic damage by causing leukostatic-leukoembolic compromise of small vessels downstream from the site of activation. PMID- 6265571 TI - Renal interstitial cell granularity in dogs with renal hypertension. AB - Hypertension was induced in dogs by the partial occlusion of one renal artery. After 12 days of hypertension the interstitial cells in the medulla of kidneys from hypertensive animals were examined by electron microscopy, and the appearance compared with interstitial cells from normal dogs. The osmiophilic granules in the cells were classified into dark and light forms, and the numbers of each counted in at least 70 cells per kidney. It was not possible to quantify the number of interstitial cells in each renal medulla. The kidneys with partially occluded renal arteries had an increased total number of granules per cell (4.93 +/- 0.51) compared with normal kidneys (0.79 +/- 0.14), and the great majority of these were dark granules (95.3% and 79.5%, respectively). In contrast the contralateral untouched kidneys had a significantly reduced number of granules per cell (0.58 +/- 0.14), and only a small proportion of the total were dark granules (31.1%). The actual number of light granules per interstitial cell was significantly increased in the untouched kidney compared with normals. PMID- 6265572 TI - Binding and functional characteristics of beta adrenergic receptors in the intact neutrophil. AB - Beta adrenergic receptors have been previously characterized in human neutrophil sonicates. In the present study the intact neutrophil has been assessed for the number and affinity of beta adrenergic binding sites by using the antagonist DNA. Agonist and antagonist potencies, characterized by their effect on DHA binding and cyclic AMP accumulation, are compared with agonist inhibition of lysosomal enzyme (beta glucuronidase) release. Criteria for beta adrenergic receptor identification were successfully demonstrated. At 30 degrees C, beta adrenergic binding was rapid (t 1/2 2 min) and reversible (t 1/2 9 min). Receptor binding was saturable, revealing approximately 900 high-affinity receptors per neutrophil with DHA concentrations of 0.1 to 10 nM. By utilizing both equilibrium and kinetic techniques, the KD was determined to be approximately 0.6 nM. Agonists and antagonists competed for DHA binding in a manner consistent with their effect on cyclic AMP generation. Rank order potency was suggestive of a beta-2 receptor: isoproterenol greater than epinephrine greater than norepinephrine. Stereoselectivity was shown by the greater potency of L-propranolol compared to the D isomer. A high degree of receptor-adenylate cyclase coupling efficiency was suggested by the observation that with only 1% receptor occupancy isoproterenol stimulated 50% maximal cyclic AMP generation. Finally, there was an excellent correlation between the isoproterenol concentration which resulted in 50% of maximal inhibition of beta glucuronidase release (Ki) and that causing 50% maximal cyclic AMP stimulation (Kact), suggestive of a close relationship between beta adrenergic-induced adenylate cyclase activation and beta adrenergic regulation of neutrophil lysosomal enzyme release. The data presented suggest that the use of the intact neutrophil for study of the beta adrenergic receptor is feasible and may provide information which is considerably more closely related to modulation of physiological function by neurohormones than is possible with disrupted cell preparations. PMID- 6265573 TI - Glomus jugulare tumours--combined treatment: part II. PMID- 6265574 TI - Glomus jugulare tumours. A review of twelve cases treated with radiotherapy. PMID- 6265575 TI - Tympanic plethysmography in glomus jugulare tumours. PMID- 6265576 TI - Radiation therapy of malignant parotid tumours. PMID- 6265577 TI - Bilateral carcinoma of the male breast: a case report. PMID- 6265578 TI - Invasive mole as a complication of artificial insemination. PMID- 6265579 TI - Studies on the corticotrophin releasing activity of a posterior pituitary extract. AB - The posterior pituitary gland is considered to be a source of a corticotrophin releasing factor(s) distinct from vasopressin. In this study, the corticotrophin releasing activity of a commercial posterior pituitary extract (Pitressin) and synthetic vasopressin were compared, using a perfused rat pituitary monolayer system. Pitressin was shown to have approximately twice the releasing activity than could be accounted for by its vasopressin content. Fractionation of the posterior pituitary extract, using high pressure liquid chromatography, showed it to contain active material co-eluting with synthetic vasopressin, and at least three other corticotrophin releasing factors. The releasing activity of the most active of these factors was investigated and was found to stimulate ACTH release in a dose-related manner. PMID- 6265580 TI - Cyclic AMP and cyclic GMP quantitation in pulp and periapical lesions and their correlation with pain. PMID- 6265581 TI - In vitro macrophage manifestation of cortisone-induced decrease in resistance to mouse hepatitis virus. AB - Genetically resistant G3H mice routinely yielded macrophages that were resistant when grown in 90% horse serum. These mice also routinely yielded macrophages that were susceptible to the same virus, MHV (PRI), in vitro after the mice had been treated with three intraperitoneal doses, of hydrocortisone. Dexamethasone and prednisolone when similarly administered also increased the susceptibility of C3H macrophages taken from the treated animal, but progesterone and testosterone did not. In addition, spleen cells from mice treated with cortisone made the resistant C3H macrophages 100 times more susceptible in vitro. Increased in vitro susceptibility induced in this way by hydrocortisone was reversed by exposure to supernatant fluid removed from cultures of concanavalin A-treated spleen cells. PMID- 6265582 TI - Chromosomal location of structural genes encoding murine immunoglobulin lambda light chains. Genetics of murine lambda light chains. AB - To determine the chromosomal localization of murine lambda light (L) chain structural genes, DNA from a panel of 11 mouse x hamster somatic cell hybrids was scored for the presence of sequences homologous to cloned lambda DNA probe molecules. Six of the hybrids had detectable lambda I and lambda II gene sequences. In all six, the full complement of murine sequences was present, and in its germline configuration. The remaining hybrids lacked any detectable murine lambda L chain gene sequences. The only mouse chromosome present in all of the positive hybrids and absent from the negative ones was number 16, allowing the assignment of lambda L chain structural genes to this chromosome. Together with the previous assignments of the kappa L chain genes to chromosome 6 and heavy chain genes to chromosome 12, this finding completes the mapping of Ig structural genes in the mouse at the chromosomal level. PMID- 6265583 TI - Mouse hepatitis virus type 4 (JHM strains). induced fatal central nervous system disease. I. genetic control and murine neuron as the susceptible site of disease. AB - Mouse hepatitis virus (JHM strain) type 4 induces acute encephalitis followed by death in many strains of laboratory mice. Immunohistochemical study in vivo and analysis of mouse neuronal cells in vitro both indicate that the target cells in this infection is the neuron. Further, examination of several inbred mouse strains and neuronal cells from them shows that disease expression is controlled by a single autosomal gene action at the level of the neuronal cell. Susceptibility is dominant but not H-2 linked. However, cultured neuronal cells and macrophages from SJL/J mice, which are resistant to this infection, fail to make significant amounts of infectious virus after an appropriate viral inoculation. Apparently the defect is not at the level of the virus-cell receptor, because these cells, in part, express viral antigens. PMID- 6265584 TI - Isolation of plasma membrane from human neutrophils and determination of cytochrome b and quinone content. AB - Analyses of plasma membrane and other subcellular fractions indicate that the primary location of cytochrome b in human neutrophils is not the plasma membrane. The procedure developed for the purification of plasma membrane from fresh human neutrophils yielded a 14-fold enrichment in the marker enzyme 5'-nucleotidase and a 10-fold enrichment in ouabain-sensitive ATPase. On sucrose density gradients, the peak density of 5'-nucleotidase activity was 1.12 g/ml, and was shifted after digitonin addition to 1.15 g/ml. Protein in the plasma membrane equalled approximately 8 percent of the whole cell protein. A b-type cytochrome was found to be present in the plasma membrane fraction at a concentration of 205 pmol/mg of protein, which is three times greater than that in the neutrophil overall. Although this cytochrome has been reported previously in the neutrophil, this is the first determination for purified plasma membrane and may indicate that b-type cytochrome has a dual localization in the human neutrophil. Differential centrifugation results suggest that the primary location is in the granules, probably specific granules. Quinone content in the plasma membrane was found to be 740 pmol/mg of protein, a concentration two times greater than in the whole cell. Such a small enhancement of quinone indicates that quinone also is not primarily located in the plasma membrane. PMID- 6265585 TI - Virus-induced diabetes mellitus. XX. Polyendocrinopathy and autoimmunity. AB - Mice infected with reovirus type 1 developed transient diabetes and a runting syndrome. The diabetes was characterized by hyperglycemia, abnormal glucose tolerance tests, and hypoinsulinemia. Inflammatory cells and viral antigens were found in the islets of Langerhans, and virus particles were seen in alpha, beta, and delta cells. The runting syndrome consisted of retarded growth, oily hair, alopecia, and steatorrhea. Inflammatory cells and viral antigens were found in the anterior, but not posterior pituitary. Electron microscopy revealed virus particles in growth hormone (GH)-producing cells and radioimmunoassay showed that the concentration of GH in the blood was decreased. Examination of sera from infected mice revealed autoantibodies that, by immunofluorescence, reacted with cytoplasmic antigens in the islets of Langerhans, anterior pituitary, and gastric mucosa of uninfected mice. Absorption studies and enzyme-linked immunosorbent assays designed to identify the reactive antigens showed that some of the autoantibodies were directed against insulin and others against GH. Reovirus type 3, in contrast to reovirus type 1, did not induce autoantibodies to GH. By use of recombinant viruses, the segment of the reovirus genome responsible for the induction of autoantibodies to GH was identified. Virus containing the S1 gene segment from reovirus type 1, which codes for the sigma 1 polypeptide (i.e., hemagglutinin), infected cells in the anterior pituitary and induced autoantibodies to GH, whereas virus containing the S1 gene segment from reovirus type 3 failed to infect cells in the anterior pituitary and did not induce autoantibodies to GH. We conclude that reovirus type 1 infection can lead to polyendocrinopathy and autoimmunity and that the S1 gene segment is required for the induction of autoantibodies to GH. PMID- 6265586 TI - The glycoprotein isolated from vesicular stomatitis virus is mitogenic for mouse B lymphocytes. AB - The glycoprotein (G protein) of VSV was purified from the intact virion by Triton X-100 extraction. The isolated G protein has been shown to be a T cell independent, B lymphocyte mitogen and polyclonal activator. Neither G protein nor the intact virion are stimulatory for murine T lymphocytes. The greater the density of G protein in lipid vesicles or the degree of aggregation of isolated G protein, the more highly stimulatory it is for murine splenocytes. As G protein is spread out in artificial vesicles, it becomes less mitogenic. It is probable that other viral components are also stimulatory since the Triton-insoluble pellet and VSV from which the G protein has been enzymatically removed retain mitogenic activity. To out knowledge, this is the first time a purified viral component has been demonstrated to be lymphocyte mitogen. PMID- 6265587 TI - Frequency analysis of cytotoxic T lymphocyte precursors in chimeric mice. Evidence for intrathymic maturation of clonally distinct self-major histocompatibility complex- and allo-major histocompatiblilty complex-restricted virus-specific T cells. AB - To study whether the thymic major histocompatibility complex (MHC) imposes a constraint on the receptor repertoire of maturating cytotoxic T lymphocyte (CTL) precursors, the restriction phenotypes of virus-specific CTL of MHC-compatible and of MHC-incompatible thymus- and bone marrow-grafted (A X B)F1 chimeric mice were compared. Dependent on the mode of in vitro sensitization, thymocytes or splenocytes of both types of chimeric mice generated Sendai virus-specific, self MHC-or allo-MHC-restricted CTL. By applying the limiting-dilution technique, the CTL-precursor (CTL-P) frequencies of self-MHC-restricted and allo-MHC-restricted virus-specific T cells as well as of alloreactive T cells were determined. The data obtained revealed that independent of MHC differences between thymus and bone marrow, the frequencies of self-MHC-restricted and allo-MHC-restricted CTL-P were comparable, and in the same older of magnitude as those previously determined in conventionally reared mice. Self-MHC-restricted, virus-specific CTL P were in a three- to fivefold excess over allo-MHC-restricted CTL-P. A segregation analysis revealed that clonally distinct CTL-P give rise to either self-restricted or allo-MHC-restricted, virus-specific CTL. Both sets were found not only in the spleen, but also in the thymus of chimeric mice, formally demonstrating the intrathymic differentiation pathway of self-MHC as well of allo MHC-restricted CTL-P. These data reveal no major constraint of the thymic MHC on the capacity of T cells to recognize viral antigens either in the context of self MHC or of allogeneic MHC products. PMID- 6265588 TI - Priming of macrophages for enhanced oxidative metabolism by exposure to proteolytic enzymes. AB - Preincubation for 10-30 min with trypsin, pronase, chymotrypsin, or papain primed macrophages to undergo a twofold to sixfold increase in oxidative metabolism, measured as release of superoxide anion or hydrogen peroxide, during stimulation by phorbol myristate acetate or ingestion of Candida parapsilosis. Preincubation of macrophages with inactivated proteases, nonenzyme proteins, or neuraminidase did not affect their oxidase response. Exposure of macrophages to proteases generated at sites of inflammation could prime these cells for a more effective oxidase response to phagocytosis or for greater tissue damage from release of toxic oxygen metabolites. PMID- 6265589 TI - J chain biosynthesis in pre-B cells and other possible precursor B cells. AB - Human cell lines that resemble precursors in the B cell lineage have been found to synthesize J chain. In vivo pulse labeling, together with in vitro translation of total cellular RNA in a wheat germ cell-free system, detected the synthesis of J chain in immunoglobulin-secreting cell lines, in a cell line with only surface IgM, as well as in the pre-B-like cell line Josh 4 and the round cell lines Josh 7 and KLM 2. The primary translation products of J chain from all of these cell lines were found to be indistinguishable from one another by serologic criteria, by relative mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, by charge as judged by alkaline-urea gel electrophoresis, and by peptide mapping. These findings suggest that the onset of J chain biosynthesis represents a relatively early event in B cell ontogeny, occurring before the development of immunoglobulin polymer-secreting cells. Its role may, consequently, be fundamental to the biosynthesis of all immunoglobulins, at different stages of B cell differentiation. PMID- 6265590 TI - Modification of sodium and potassium channel gating kinetics by ether and halothane. AB - The effect of ether and halothane on the kinetics of sodium and potassium currents were investigated in the crayfish giant axon. Both general anesthetics produced a reversible, dose-dependent speeding up of sodium current inactivation at all membrane potentials, with no change in the phase of the currents. Double pulse inactivation experiments with ether also showed faster inactivation, but the rate of recovery from inactivation at negative potentials was not affected. Ether shifted the midpoint of the steady-state fast inactivation curve in the hyperpolarizing direction and made the curve steeper. The activation of potassium currents was faster with ether present, with no change in the voltage dependence of steady-state potassium currents. Ether and halothane are known to perturb the structure of lipid bilayer membranes; the alterations in sodium and potassium channel gating kinetics are consistent with the hypothesis that the rates of the gating processes of the channels can be affected by the state of the lipids surrounding the channels, but a direct effect of ether and halothane on the protein part of the channels cannot be ruled out. Ether did not affect the capacitance of the axon membrane. PMID- 6265591 TI - Inactivation of potassium current in squid axon by a variety of quaternary ammonium ions. AB - The characteristics of potassium channel block by a diverse group of quaternary ammonium (QA) ions was examined in squid axons. Altering the size and nature of the head and/or tail groups of the QA ions applied internally produced only quantitative differences in the potassium current block. Although their entry rate is diminished, compounds with head groups as large as 11 X 12 A are capable of occluding the channel, whereas the smallest QA ions, with head groups approximately 5 X 6 A, are not potent blockers. When one or three terminal hydrogens of the head group were replaced by hydroxyl moieties, the compound's blocking ability was diminished, suggesting that QA binding is not improved by hydrogen bonding at these positions. QA ions bound to their site within the potassium channel with 1:1 stoichiometry, and the site is perhaps 20% or more of the distance through the membrane electric field. Raising external potassium concentration did not alter the steady-state or kinetic features of the QA block of outward potassium currents; however, increasing temperature or adding Ba2+ internally increased the rate of decay of the QA-blocked currents. From the structure-function analysis of the QA ions, projections concerning both the architecture of the potassium channel's inner mouth and the significance of various chemical constituents of the ions were made. The potassium channel may now be pictured as having a wider mouth (up to 11 X 12 A) extending to the QA binding site and then narrowing quickly to the region of channel selectivity. Important alterations that improve the blocking ability of the compounds include: (a) lengthening the alkyl hydrocarbon tail group (up to 10 carbon), (b) lengthening a second hydrocarbon chain of the head group (e.g., decyldimethylphenylammonium bromide [C10DM phi]), and (c) adding a carbonyl moiety to the tail (e.g., ambutonium). PMID- 6265592 TI - Probes of the conduction process of a voltage-gated Cl- channel from Torpedo electroplax. AB - The open-channel conductance properties of a voltage-gated Cl- channel derived from Torpedo californica electroplax and incorporated into planar bilayers were studied by several approaches. In neutral bilayers the channel conductance saturates with Cl- activity according to a rectangular hyperbolic relation with a half-saturation activity of 75 mM and a maximum conductance of 32 pmho. The observation of identical behavior in charged membranes implies that ions permeating the channel do not sense the surface potential of the bulk membrane. The Cl-:Br- permeability ratio, measured under biionic conditions, is independent of salt concentration. SCN- ion reversibly blocks the channel. The voltage dependence of the block implies the existence of two separate blocking sites within the channel: one accessible from the cis side only (the side to which vesicles are added) and the other accessible from the trans side only. The block at each site is competitive with Cl-. The results are consistent with a single ion Eyring model of the conduction process in which the ion must traverse three kinetic barriers as it permeates the channel and in which the channel can accommodate at most one ion at a time. PMID- 6265594 TI - Effects of tetraethylammonium on potassium currents in a molluscan neurons. AB - The effects of tetraethylammonium (TEA) on the delayed K+ current and on the Ca2+ activated K+ current of the Aplysia pacemaker neurons R-15 and L-6 were studied. The delayed outward K+ current was measured in Ca2+-free ASW containing tetrodotoxin (TTX), using brief depolarizing clamp pulses. External TEA blocks the delayed K+ current reversibly in a dose-dependent manner. The experimental results are well fitted with a Michaelis-Menten expression, assuming a one-to-one reaction between TEA and a receptor site, with an apparent dissociation constant of 6.0 mM. The block depends on membrane voltage and is reduced at positive membrane potentials. The Ca2+-activated K+ current was measured in Ca2+-free artificial seawater (ASW) containing TTX, using internal Ca2+ ion injection to directly activate the K+ conductance. External TEA and a number of other quaternary ammonium ions block the Ca2+-activated K+ current reversibly in a dose dependent manner. TEA is the most effective blocker, with an apparent dissociation constant, for a one-to-one reaction with a receptor site, of 0.4 mM. The block decreases with depolarization. The Ca2+-activated K+ current was also measured after intracellular iontophoretic TEA injection. Internal TEA blocks the Ca2+-activated K+ current (but the block is only apparent at positive membrane potentials), is increased by depolarization, and is irreversible. The effects of external and internal TEA can be seen in measurements of the total outward K+ current at different membrane potentials in normal ASW. PMID- 6265593 TI - Activation-inactivation of potassium channels and development of the potassium channel spike in internally perfused squid giant axons. AB - A spike that is the result of calcium permeability through potassium channels was separated from the action potential is squid giant axons internally perfused with a 30 mM NaF solution and bathed in a 100 mM CaCl2 solution by blocking sodium channels with tetrodotoxin. Currents through potassium channels were studied under voltage clamp. The records showed a clear voltage-dependent inactivation of the currents. The inactivation was composed of at least two components; one relatively fast, having a time constant of 20--30 ms, and the other very slow, having a time constant of 5--10 s. Voltage clamp was carried out with a variety of salt compositions in both the internal and external solutions. A similar voltage-dependent inactivation, also composed of the two components, was recognized in all the current through potassium channels. Although the direction and intensity of current strongly depended on the salt composition of the solutions, the time-courses of these currents at corresponding voltages were very similar. These results strongly suggest that the inactivation of the currents in attributable to an essential, dynamic property of potassium channels themselves. Thus, the generation of a potassium-channel spike can be understood as an event that occurs when the equilibrium potential across the potassium channel becomes positive. PMID- 6265595 TI - Transposable gentamicin resistance in IncW plasmids from Hammersmith Hospital. AB - A transposon, Tn733, encoding the gentamicin acetyltransferase AAC(3) was found on two gentamicin R plasmids of IncW at Hammersmith Hospital. Transposon TN733 has a molecular mass of 5.8 megadaltons and gives a characteristic 2.4 megadalton fragment on digestion with EcoRI. The appearance of gentamicin resistance on a transposon will increase the chances of spread of this gene. PMID- 6265596 TI - The role of superoxide and hydroxyl radicals in the degradation of hyaluronic acid induced by metal ions and by ascorbic acid. AB - Purified commercial hyaluronic acid contains significant amounts of iron. Addition of Fe2+ to solutions of it causes depolymerization, which is inhibited by catalase and scavengers of the hydroxyl radical (. OH) but not by superoxide dismutase. Fe3+ is ineffective. Ascorbic acid also depolymerizes hyaluronic acid, apparently because it can reduce Fe3+ in the reaction mixtures to Fe2+. Ascorbate induced depolymerization is inhibited by the specific iron chelator desferrioxamine, by catalase, and by scavengers of the hydroxyl radical. The relevance of these observations to rheumatoid arthritis and inflammatory joint diseases is discussed. PMID- 6265597 TI - GABA-benzodiazepine-barbiturate receptor interactions. PMID- 6265598 TI - Possible role of cyclic AMP in the receptor-mediated regulation of glycosyltransferase activities in neurotumor cell lines. AB - Exposure of mouse neuroblastoma cell line N4TGl to opiates or [D-Ala2,D-Leu5] enkephalin produced a naloxone-reversible inhibition of cyclic AMP synthesis and prevented, in a concentration-dependent manner, the formation of both ganglioside GM2 (GalNAc-[NeuNAc]-Gal-Glc-ceramide) from GM3 (NeuNAc-Gal-Glc-ceramide) and ganglioside GM1 (Gal-GalNAc-[NeuNAc]-Gal-Glc-ceramide) from GM2 in cell-free extracts. In contrast, the receptor-mediated elevation of intracellular cyclic AMP levels by agents such as prostaglandin E1 (in the presence of isobutylmethylxanthine) or the addition of the cyclic AMP derivatives (dibutyryl cyclic AMP) markedly stimulated the activities of UDP-GalNAc:GM3,N acetylgalactosaminyltransferase and UDP-Gal:GM2,galactosyltransferase. An overall increase in the synthesis of gangliosides more complex than GM3 was also observed in the mouse neuroblastoma x hamster brain explant hybrid cell line NCB-20 following elevation of cyclic AMP levels by treatment with serotonin and pargyline. The data presented support the hypothesis that cyclic AMP may have a role in the regulation of sialoglycosphingolipid biosynthesis. PMID- 6265599 TI - Mutually independent cyclic AMP and sodium responses to nerve growth factor in embryonic chick dorsal root ganglia. PMID- 6265601 TI - Uncompacted myelin lamellae in dysglobulinemic neuropathy. AB - Uncompacted lamellae, located preferentially in inner layers of myelin sheath, were observed in biopsied sural nerves of 3 cases of dysglobulinemic neuropathy, in which the main pathological findings of myelinated fibers were those of segmental demyelination and remyelination, and axonal degeneration with concurrent marked decrease of myelinated fiber density. The presence of uncompacted myelin lamellae is well explained by the irregular distribution of adaxonal, incisural and paranodal cytoplasm of the Schwann cell. PMID- 6265600 TI - Evaluation of the drug-induced morphological differentiation of rat glioma cells (C-6) from the aspects of S-100 protein level and con A binding pattern. AB - The intracellular content of the nervous system specific protein S-100 began to increase with 4 days latency following the morphological differentiation of cultured rat glioma cells (C-6) with 1 mM dibutyryl cyclic AMP (dbcAMP), rising to approximately 10-fold over the control level at 15 days after the treatment. The concanavalin A (Con A) binding pattern on the external cell surface of C-6 cells exposed to dbcAMP appeared as a smooth layer of 40-60 nm thickness whereas that of control cells was irregularly thick and patchy. The correlation between morphological and biochemical changes of C-6 cells after dbcAMP treatment is discussed in relation to the mechanism controlling the differentiation of glioma cells. PMID- 6265602 TI - Disulfiram neuropathy. A morphometric study of sural nerve. AB - This report describes peripheral nerve morphology in 3 patients whose acute polyneuropathy followed disulfiram therapy. In all patients a combination of axonal degeneration with segmental demyelination and remyelination was seen, suggesting a varying degree of toxicity to both cytons and Schwann cells. The observed randomness of abnormal internodes argued against primary axonal atrophy and secondary demyelination. While large myelinated fibres were preferentially lost, ultrastructural studies also suggested degeneration of unmyelinated fibres. Because of high chloral consumption at the onset of peripheral nerve disease in 2 patients, the possibility of disulfiram-chloral interaction was considered. Present evidence suggests that the combined use of chloral or its derivatives with disulfiram is best avoided. PMID- 6265603 TI - Experimental ethambutol neuropathy in rats. Morphometric and teased-fiber studies. AB - Eight rats were given 500 mg/kg body weight of the antituberculous drug ethambutol orally every day for 3 months (group A), and 7 took 150 mg/kg of the drug for 9 months (group B). The sciatic nerves at midthigh level and the posterior tibial nerves at ankle level were studied with morphometric examination and teased-fiber method. The number of myelinated fiber/mm(2) of fascicular area was significantly reduced in both sciatic and posterior tibial nerves of group B. The pattern of frequency distribution of myelinated nerve fiber diameters of both groups was not different from that of the controls. Teased-fiber study revealed that many fibers were undergoing axonal degeneration in both groups A and B. In addition, regenerating fibers after axonal degeneration were observed in group B. These results showed that the predominant pathologic change in ethambutol neuropathy was axonal degeneration and that regeneration was already occurring in the animals taking a small dose of the drug for a long period. The fact that the degree of pathologic change was rather more severe in the sciatic nerve than in the posterior tibial nerve indicated that this was not a "dying-back" neuropathy. PMID- 6265604 TI - Electrophysiological changes of HSV-1-infected dorsal root ganglia neurons in culture. AB - Dissociated rat dorsal root ganglion cultures were infected with herpes simplex virus type 1 and studied electrophysiologically throughout the course of infection. Alterations in the electrical parameters of the action potentials of these neurons occurred as early as 4 hours post infection. The maximum rate of rise, spike amplitude, and overshoot were decreased, and the full width at half maximum and resting membrane potential were increased. At 6 hours post infection there is a movement back to normal values for these parameters. This reversal is transient, however, and the types of alterations seen at 4 hours post infection are more pronounced at 12 hours post infection. The first morphological alterations occur at 16 hours post infection, at which time less than 50% of the neurons impaled produced action potentials. Application of cyclohexamide to inhibit protein synthesis 1 hour post infection prevented electrophysiological changes normally seen at 4 hours and 6 hours post infection. It is concluded that the sodium conductance is specifically reduced by acute HSV infection, and that this reduction is attributed to viral specific or modified host cell protein synthesis. PMID- 6265605 TI - Descending inhibition from medial and lateral midbrain of spinal dorsal horn neuronal responses to noxious and nonnoxious cutaneous stimuli in the cat. PMID- 6265606 TI - Interganglionic communication by spiking and nonspiking fibers in same neuron. PMID- 6265607 TI - Craniosynostosis in vitamin D-resistant rickets. A mouse model. AB - Craniosynostosis and associated craniofacial deformities, such as frontal bossing, often occur as symptoms of vitamin D-resistant rickets in children. Similar skull deformities develop in mice with X-linked dominant hypophosphatemia, the most common form of vitamin D-resistant rickets. These mice have a short, wide, high neurocranium, which suggested an inhibition of coronal suture growth. To study this question, we compared histologically the postnatal development of the coronal sutures in normal and hypophosphatemic mice between 1 and 13 weeks of age. Premature fusion of the coronal suture occurred in hypophosphatemic mice by 4 weeks of age. The proportion of the suture obliterated by bone varied among individual animals, but craniosynostosis was present in all animals studied at 4 weeks and older. Fusion of the coronal suture did not occur through 13 weeks of age in any of the normal mice studied. The x-linked hypophosphatemic mouse is an animal model that can be used to study the role of vitamin D-resistant rickets in the development of craniosynostosis, to relate craniosynostosis to the development of associated skull deformities, and to test new treatment procedures. PMID- 6265608 TI - Decomposition of Tc-99m pyrophosphate by peroxides in pertechnetate used in preparation. AB - We describe an investigation of the stability of Tc-99m pyrophosphate (Tc-99m PPi). We hve shown that addition of exogenous hydrogen peroxide to Tc-99m PPi can initiate the oxidation of the complex, giving rise to 95% unbound pertechnetate. The presence of endogenous hydrogen peroxide in the sodium pertechnetate used in the preparation of Tc-99m PPi has been thought to influence its stability. We have prepared it using pertechnetate solutions of different specific activities. After preparation, an alumina column was used to detect free 99mTcO4-. The Tc-99m PPi and Na99mTcO4 solutions were then assayed by iodometric titration for hydrogen peroxide, which was detected in the pertechnetate solutions. The higher the specific activity of the solution used for the tracer preparation, the faster was the production of free pertechnetate. PMID- 6265609 TI - Detection of ectopic gastric mucosa in Meckel's diverticulum and in other aberrations by scintigraphy: I. Pathophysiology and 10-year clinical experience. AB - Ten years of clinical experience with pertechnetate (Tc-99m) scintigraphy has proven its validity for the diagnosis of ectopic gastric mucosa in bleeding Meckel's diverticulum and other congenital anomalies. Careful patient preparation and a standardized technique based on sequential gamma imaging has resulted in an overall sensitivity of 85%. Experience in differentiating "nonspecific" accumulations of pertechnetate from true ectopic gastric mucosa had increased the specificity to 95%. When we consider all the studies reported (954) with a surgical or clinical diagnosis, the accuracy of the method is calculated at 98%. When only surgically proven cases are analyzed, the calculated accuracy is 90%. Pertechnetate excretion by the mucoid cells of gastric mucosa is the basis of this test. The effect of drugs and hormones on the test has been studied in animals and in patients. The findings suggest that an improvement can be achieved by the use of cimetidine, pentagastrin, or glucagon. PMID- 6265610 TI - Myocardial infarct imaging: superiority of inorganic agents over organic diphosphonates. PMID- 6265611 TI - [Intranasal mucociliary homeostasis (author's transl)]. PMID- 6265612 TI - Histochemical studies of hepatocellular carcinomas in the rat induced by aflatoxin. AB - A histochemical study has been done on a group of 18 hepatocarcinomas induced by aflatoxin. One hundred per cent, incidence of hepatocarcinomas is induced by feeding 5 p.p.m. aflatoxin for 6 weeks. The carcinomas were trabecular hepatocarcinomas with a mixed adenomatous pattern and showed considerable variation in histochemical reactions throughout the lesions. There was a patchy distribution of glycogen and glucose-6-phosphate and the membrane ATPase was present along much of the canalicular border of the cells but with an abnormal and tortuous pattern. Aniline hydroxylase was present in varying amounts in both trabecular and adenomatous carcinomas. It is concluded that the histological variants of hepatocarcinoma are all derived from hepatocytes, but no unique changes were observed related to the progress involved in malignant neoplasia. The observations form a basis for comparison with early lesions seen prior to the recognition of carcinoma. PMID- 6265613 TI - The biological behaviour of gastric cancer. AB - A characterisation of the biological behaviour of gastric carcinoma was attempted by relating the histological classification to the mean number of metastases for each case (metastatic index). The material was chosen from a consecutive series of 294 gastric cancer autopsies in which only conservative therapy had been given or in which the cancer was first diagnosed at autopsy. According to the extent of metastasis it was possible to divide the nine histological types into two groups of limited invasiveness and generalised invasiveness. Unfavourable biological behaviour of the cancer was determined by the presence of the latter group of histological types in the primary site even in cases where this histological type formed the minor component of the tumour. The variation in histology within the primary tumour and between the primary site and the metastatic sites was related both to histological affinities and to the metastatic index associated with the primary site histology. It is suggested that this dual classification system adds significantly to our understanding of the natural history of gastric cancer. PMID- 6265614 TI - Long-term treatment of familial hypophosphatemic rickets with oral phosphate and 1 alpha-hydroxyvitamin D3. AB - Combined treatment with oral phosphate and 1 alpha (OH)D3 was carried out in nine children with familial hypophosphatemic rickets. All nine had positive responses over a four- to six-year period as judged by healing of rickets, change in growth rate, decrease in alkaline phosphatase activity, and symptomatic improvement. In two patients therapy was stopped for a short time because of hypercalcemia. In one patient in whom therapy was effective there was a significant reduction in creatinine clearance which necessitated cessation of treatment. The results of this study suggest that combined treatment with 1 alpha(OH)D3 and oral phosphate is an effective form of therapy for this condition, but that the balancing of these two modalities of therapy in each patient is essential if hypercalcemia and hypercalciuria, on the one hand, and secondary hyperparathyroidism, on the other, are to be avoided. A simple means of balancing these therapeutic modalities is suggested. PMID- 6265615 TI - Vitamin D dependency: replacement therapy with calcitriol? AB - Nine patients with vitamin D-dependency type I were studied. We observed that treatment with large doses of vitamin D altered the phenotypic expression of the disease, thus making a delayed diagnosis difficult. At the time of entry, eight children had hypocalcemia, and seven had hypophosphatemia. Elevated serum immunoreactive parathyroid hormone and low (less than 3 SD from control mean) 1 alpha,25-dihydroxyvitamin D values were constant findings, with no vitamin D deficiency. Despite the elevated serum iPTH, three children had normal urinary phosphate excretion and five had normal urinary cAMP excretion. In the five children tested before treatment, there was no significant change in renal phosphate excretion during an acute parathyroid hormone infusion, although in all a significant rise of urinary cAMP occured. Treatment with calcitriol (0.25 to 2 microgram/day) returned all the biochemical values to normal within four months. In two patients, both supplemented with vitamin D, histomorphometric analysis of iliac crest biopsies revealed severe osteomalacia. After nine and ten months of treatment with calcitriol, there was histologic evidence for improvement of bone mineralization. Since calcitriol requirements may vary during the course of treatment, careful monitoring of biochemical variables is essential. PMID- 6265616 TI - Diarrhea caused by Shigella, rotavirus, and Giardia in day-care centers: prospective study. AB - We conducted a 19-month prospective study of children attending 20-day-care centers to determine the occurrence, causes, and transmission of gastroenteritis among children, staff, and family members. Nine centers had 15 outbreaks of diarrhea involving 195 patients. An enteropathogen was identified in all outbreaks. Shigella was detected in five outbreaks, rotavirus in two, giardia in one, and in the remaining seven multiple enteropathogens were identified. Rotavirus and Giardia occurred only in children less than 3 years of age; shigellosis occurred at all ages. In six DCC 68 single cases of diarrhea were not associated with an outbreak; an enteropathogen was identified in only three (4%) persons. Thirty-four family members (11%) developed diarrhea associated with the occurrence of gastroenteritis in children in six DCC evaluated for this problem. Secondary attack rates of diarrhea in families according to organisms identified in the DCC outbreaks were: Shigella 26%, rotavirus 15%, and G. lamblia 17%. DCC may play an important role in the epidemiology and transmission of gastroenteritis in the United States. PMID- 6265618 TI - Rickets: primary hypophosphatemic and vitamin D-dependent varieties. PMID- 6265617 TI - Serum angiotensin-converting enzyme activity in normal children and in those with sarcoidosis. AB - Serum angiotensin-converting enzyme was measured in 185 children of different ages, in 32 normal adults, in 21 children with sarcoidosis, and in 36 children with other diseases. Children had higher serum ACE volumes than did adults; an intermediate level was absorbed in adolescents. Serum ACE values did not vary according to sex. Children with sarcoidosis had significantly elevated serum ACE levels that closely reflected the activity of the disease. Our results indicate that serum ACE is useful in confirming the diagnosis of sarcoidosis in childhood, and is of greater value as a sensitive indicator for following the course of the disease and the effectiveness of steroid therapy. PMID- 6265619 TI - Elevated serum 1,25 dihydroxyvitamin D concentrations in rickets of very low birth-weight infants. AB - Elevated 1,25 dihydroxyvitamin D concentrations were found in five VLBW infants who developed rickets at two to three months postnatal age or term postconceptual age; 25 hydroxyvitamin D concentrations were low. Bone mineralization was found to be extremely low as measured by infant-adapted direct photon absorptiometry. After treatment with a formula supplemented with additional Ca and P, there was a rapid improvement in bone mineralization with a concomitant decrease of 1,25(OH)2D to normal adult values, whereas 250HD values increased and parathyroid hormone values decreased. In the VLBW infants studied, we suggest that rickets may be caused by Ca and P deficiency rather than by a deficiency of vitamin D metabolism. PMID- 6265620 TI - Major hepatic tumor resection using profound hypothermia and circulation arrest. AB - In spite of recent reports of more aggressive investigation and treatment of malignant liver tumors in infants and children, there is still an alarming morbidity and mortality in the operative aspect of this tumor. Our operative approach to partial hepatectomy follows that laid down by many authors, but we seem to have the same intraoperative problems in removing the huge tumor confined to one liver lobe. The blood loss in such operations may equal or exceed the child's blood volume while intraoperative cardiac arrest is not unknown. The bleeding can be most acute in the course of the retrohepatic caval and hepatic veins dissection. Once bleeding becomes excessive, the dissection must continue in a hurried fashion leading to the above problems. Since 1977, six children have been admitted to our hospital with huge malignant liver tumors involving almost all of one liver lobe and part of the other. Each was explored through a long midline abdominal incision finding what was felt to be a resectable liver tumor. The incision was then carried upwards via a sternal split or a right thoracoabdominal incision and the liver mobilized. The patient was then put on cardiopulmonary bypass and cooled to a rectal temperature below 20 degrees C. Circulation arrest at this low temperature provided 1 hr or less of bloodless dissection, and an extended hepatic lobectomy was easily carried out. The patients were rewarmed on bypass and normal hemodynamics restored. Bleeding from the liver edge was controlled and the remainder of the operation completed. What was previously the most difficult aspect of a liver tumor operation has become the easiest part of the entire procedure. This operative approach is recommended in highly selected large tumor cases. PMID- 6265621 TI - Effect of poly-2-vinylpyridine-N-oxide and sucrose on silicate-induced hemolysis of erythrocytes. AB - The biological activity of montmorillonite, palygorskite, kaolinite, chrysotile, and silica was examined using in vitro hemolysis of erythrocytes. The hemolytic potency was in the order montmorillonite greater than silica greater than palygorskite greater than chrysotile greater than kaolinite. The polymer poly-2 vinylpyridine-N-oxide inhibited hemolysis caused by montmorillonite, palygorskite, kaolinite, and silica, but it was less effective with chrysotile. The extent of polymer binding to the silicates and red blood cells was measured by UV spectroscopy. When sucrose was substituted for the saline solution as the incubating medium, hemolysis was eliminated in all systems except chrysotile erythrocyte, where it was enhanced. The results indicate that both hydrogen bonding and ionic interactions between silicate surfaces and the erythrocyte membrane are important in the hemolytic process. PMID- 6265622 TI - Action of lithium on the adrenergic nerve ending. AB - The effect of lithium on adrenergic neurotransmission was investigated using the lateral saphenous vein of the dog as a model of the neuroeffector process. Helically cut vein strips were mounted in either an organ bath where tension was recorded or in a superfusion system where both tension and the overflow of [3H]norepinephrine and its metabolites were determined. Lithium was used at both therapeutic (0.5-1.5 mEq/l) and toxic (2.5-14.4 mEq/l) concentrations. Lithium had no effect on basal tension or overflow [3H]norepinephrine. At therapeutic concentrations, the neuronal amine uptake mechanism was augmented, whereas at toxic concentrations monoamine oxidase was inhibited. In therapeutic concentrations, lithium attenuated the response of the adrenergic nerve ending to electrical stimulation (0.5-10 Hz). This response was due in part to the augmentation of the neuronal amine uptake mechanism. At toxic concentrations, responses to low frequency (0.2-1.0 Hz) electrical stimulation were augmented, whereas those at higher frequencies (5-10 Hz) were attenuated. Inhibition of monoamine oxidase by lithium accounted for only a part of the augmented overflow of transmitter and subsequent contractile response since inhibition of monoamine oxidase did not prevent the augmentation by lithium of [3H]norepinephrine overflow. The mechanism by which lithium in both therapeutic and toxic concentrations reduces transmitter overflow and subsequently contractile responses remains to be elucidated. Thus, lithium alters the disposition and release of norepinephrine and, as a result, affects adrenergic neurotransmission. PMID- 6265623 TI - A radioimmunoassay for 5-methyltetrahydrohomofolate. AB - A radioimmunoassay for 5-methyltetrahydrohomofolate has been developed by using antibody induced in rabbits by 5-methyltetrahydrohomofolate-bovine serum albumin conjugates. The labeled drug was prepared by condensing it with [3H]histamine or [125I]histamine. The assay employing either isotope was simple and reproducible and had identical sensitivities. The specificity of the antibody was characterized by comparing the effectiveness of various related compounds in displacing labeled 5-methyltetrahydrohomofolate from the binding site of the antisera. At concentrations up to 1000 microgram/ml, homofolate acid, tetrahydrohomofolic acid, folic acid and methotrexate showed no competition for the binding. 5-methyltetrahydrofolic acid and 5-formyltetrahydrofolic acid cross reacted with the antisera; the concentrations producing 50% binding inhibition were 2.8 and 24 microgram, respectively, as compared to 0.01 microgram for 5 methyltetrahydrohomofolate. The assay can be used for measuring the drug in plasma and tissues. This study supports its usability for clinical pharmacologic studies. PMID- 6265624 TI - The effect of lanthanum ions on acetylcholine in frog muscle. AB - 1. Frog sartorius muscles were treated with an irreversible cholinesterase inhibitor and then incubated in Ringer with 2 mM-LaCl3. The amounts of ACh in the tissue and medium were assayed by mass fragmentography, miniature end-plate potentials (min. e.p.p.s) were recorded and the end-plate was investigated by electron microscopy. 2. Addition of La3+ caused in normal, but not in denervated, muscles a discharge of both min. e.p.p.s and chemically detectable ACh. After 30 min both min. e.p.p.s and ACh release decreased. Between 4 and 5 hr after the addition of La3+ min. e.p.p.s had practically ceased and the rate of ACh release was almost back to that in the absence of La3+. 3. La3+ caused a 50% reduction in the ACh content of the tissue within the first 30 min; thereafter ACh gradually increased to 110% by 5 hr. At this time synaptic vesicles were practically absent in most terminals. The ACh was predominantly located in the end-plate regions of the muscles, before as well as after the incubation with La3+. ACh in end-plate free parts of the muscles was unchanged by La3+. 4. Hemicholinium-3 inhibited the synthesis of ACh in the muscles, but it had almost no influence on La3+-induced ACh release. 5. From these and other results, it is concluded that the ACh released by La3+ originates exclusively from the nerve terminals, that most likely this ACh is released via exocytosis from synaptic vesicles, and that the synthesis of ACh following the release of ACh takes place in the nerve terminals. The results further indicate that in freshly excised muscle the greater part (80 90%) of the ACh contained in the nerve terminals is located in the vesicles. PMID- 6265625 TI - Effects of cyclic AMP, ouabain and furosemide on ion transport in isolated canine gastric mucosa. AB - 1. Cyclic AMP (10 mM), present in the serosal solution of isolated dog gastric mucosa, increased potential difference (p.d.), short-circuit current (ISC), net flux of Na+ from the mucosal to serosal side, and the unidirectional flux of K+ from the mucosal to serosal side. Cyclic AMP did not stimulate H+ or Cl- secretion. 2. Dibutyryl cyclic AMP (DBcAMP, 1 mM) or theophylline (2 mM), present in the serosal solution, stimulated H+ and Cl- secretion, decreased p.d., ISC and electrical resistance. These compounds had no effect on Na+ transport. The stimulatory effect of DBcAMP on H+ secretion was still present after pretreatment with cimetidine or atropine. 3. Ouabain abolished both the p.d. and ISC of the histamine-stimulated gastric mucosa. The mucosal to serosal flux of Na+ and the serosal to mucosal flux of Cl- were significantly decreased in the presence of ouabain. Ouabain caused an increase in the serosal to mucosal flux of K+ and high concentrations caused a significant reduction in H+ secretion. 4. Furosemide (10( 4) M) decreased p.d., ISC and net flux of Na+. Higher concentrations inhibited the net flux of Cl- from the serosal to mucosal side. 5. These results suggest that in isolated dog gastric mucosa, (1) both DBcAMP and theophylline may increase intracellular cyclic AMP to stimulate H+ and Cl- secretion, (2) cyclic AMP, outside the serosal membrane, stimulates active transport of Na+; in contrast, ouabain inhibits this active process predominantly, (3) the selective action of furosemide on Na+ transport indicates that Na+ and Cl- move via separate transport pathways across the serosal border. PMID- 6265628 TI - Self-concept in children with and without physical disabilities. PMID- 6265626 TI - The influence of the infusion of noradrenaline on plasma cortisol levels in man. AB - 1. Noradrenaline was infused into normal resting male subjects for consecutive 20 min periods at 3, 7.5 and 15 microgram min-1. At the end of the 1 hr of noradrenaline infusion, total catecholamine levels were in the range 4-6 microgram l.-1, comparable with those observed in severe exercise. 2. At all rates of infusion there were marked elevations of arterial blood pressure leading to reflex reductions of heart rate. Blood flow in the foot was reduced but blood flow in the calf was unaffected. Following the infusion, blood pressure rapidly returned to normal but the heart rate was raised by some 15 beat min-1 higher than the preinfusion control for at least 90 min. 3. Plasma cortisol tended to decrease slightly during the noradrenaline infusion but in twelve out of seventeen experiments it began to rise 30-75 min after termination of the infusion, reaching values 5-15 microgram 100 ml.-1 higher than those at the end of the noradrenaline infusion. Simultaneous rises in plasma aldosterone level were observed in those experiments in which it was measured. 4. Because of the long delay in the onset of hypercortisolaemia it is suggested that this is initiated not by the noradrenaline levels per se but by some physiological readjustments to the rapid fall in plasma noradrenaline level when the infusion was discontinued. The nature of these changes was not determined. 5. It is concluded that the elevated levels of plasma noradrenaline observed during exercise are not responsible for the synchronous increases in cortisol secretion. PMID- 6265629 TI - Manic depression: an overview. PMID- 6265627 TI - Asymmetry currents in the mammalian myelinated nerve. AB - 1. Asymmetrical displacement currents were recorded in the rabbit node of Ranvier by averaging the currents associated with depolarizing and hyperpolarizing pulses in the temperature range 15-25 degrees C with the ends of the fibre cut in 160 mM CsCl. 2. The identification of the asymmetrical currents as intramembranous current is supported by the findings that (a) the "on' and "off' current transients were equal for short and small depolarizing pulses and (b) the total charge displaced reached saturation at (32-111 x 10(-15) C/node) when sufficiently large depolarizations were applied. 3. After a large depolarization to around 50 mV, the "off' response consisted of a fast phase followed by a slow phase. Lengthening the depolarization reduced the size of the fast response but enhanced the slow response. 4. The steady-state rearrangement of the charges can be described by a Boltzmann distribution of charges with an effective valence of 1.86 and a midpoint potential of -33 mV. The time course of rearrangement of these charges following a change in membrane potential could be fitted reasonably well with a single exponential though a double exponential might have been better at large depolarizations. 5. The steady-state activation curve for Na conductance was measured with various procedures to eliminate the effects of series resistance, which include decreasing peak Na current by TTX, and electronic compensation of the series resistance. The measured steepness of the Na activation curve corresponds to moving a minimum charge of about 5e to open each Na channel at 22.7 degrees C. 6. The time constant (Tm) for activation of Na current and time constant (Ton) for declining phase of the asymmetry current were of the same order of magnitude but not identical over the potential range -50 to +25 mV. 7. The time course of charge displacement determined from the asymmetry current occurred earlier than did Na activation. Raising the charge displacement curve to second or third power did not yield a curve that matched the time course of Na activation. 8. If all the observed asymmetrical currents are related to the Na-gating system, an upper limit for the number of Na channels per rabbit node is 82,000 and a lower limit for the single channel conductance is 9.8 pS at 18.8 degrees C. PMID- 6265630 TI - Counseling the alcoholic client. AB - In all helper-helpee relationships, the experiencing of the uniqueness of each person is crucial. Each alcoholic is a person and alcohol dependence is but one plane of that person's being. Obtaining current information about alcoholism enables the professional nurse to deal with the disease in a systematic fashion. The personhood of each alcoholic must be met with creativity that focuses on the entire scope of potential as the conflict "I can't drink" changes to resolution, and increasing fullness of life becomes the issue. PMID- 6265631 TI - Assertion therapy: the nurse and the psychiatric patient in an acute, short-term hospital setting. PMID- 6265632 TI - The chemotherapy of protozoal infections: whither? PMID- 6265633 TI - Biological functions and receptor binding activities of equine chorionic gonadotrophins. AB - The role of equine chorionic gonadotrophin (CG, formerly termed Pregnant Mare serum Gonadotrophin, PMSG) in maintaining equine pregnancy was investigated by examining the effects of this hormone on the maternal ovaries during early gestation and relating these findings to the receptor binding activities of CG in vitro. Measurement of plasma progestagen profiles in mares and donkeys carrying horse, donkey, mule ( female horse X male donkey) and hinny (female donkey X male horse) conceptuses confirmed that CG induced several secondary ovulations and thus maintained maternal progestagen concentrations. However, in mares carrying horse and mule conceptuses and in donkeys carrying donkey conceptuses the growth of the follicles that gave rise to the secondary corpora lutea occurred before CG was secreted and the CG did not express any FSH-like activity. Nevertheless, in donkeys carrying hinny pregnancies the CG secreted by the hinny conceptus stimulated massive follicular growth in addition to luteinization, presumably because of an enhanced sensitivity of donkey ovaries to hinny CG which, as demonstrated in previous studies, is a mixture of horse and donkey CG and hence has considerably more FSH-like activity than normal donkey CG. In-vitro receptor binding experiments showed that both horse and donkey gonadal tissues possessed a low binding affinity for horse CG compared to that exhibited by equivalent gonadal tissues of other species. Furthermore, horse CG bound with low, but significant, affinity to horse and donkey LH receptors and donkey FSH receptors, but exhibited negligible binding to horse FSH receptors. We suggest that in equids the receptor-mediated refractoriness to the gonadotrophic activities of the intraspecific chorionic gonadotrophin protects the ovaries during pregnancy. PMID- 6265634 TI - Changes in adenosine 5'-triphosphate, adenylate energy charge and adenosine 3'5' cyclic monophosphate during the freezing of buffalo semen. AB - In freshly ejaculated buffalo semen (N = 4) there were 24.61 +/- 5.28 nmol ATP and 40.39 +/- 5.94 nmol total adenylate/10(8) spermatozoa, and 97.75 +/- 7.06 pmol cAMP/10(9) spermatozoa. The semen was frozen in 4 steps (I, dilution; II, cooling; III, glycerolization and equilibration; IV, freezing and thawing). Motility, ATP, total adenylate and cAMP were significantly lower after Step IV than after Step I. Motility and ATP concentration were significantly correlated in egg-yolk--Tris (r = 0.530, P less than 0.05), skim milk--egg yolk (r = 0.754, P less than 0.01), egg yolk--citrate--glucose (r = 0.784, P less than 0.01) and citric acid--whey (r = 0.551, P less than 0.05). Cyclic AMP and motility in egg yolk--Tris were also correlated (r = 0.714, P less than 0.01). The adenylate energy charge was stable in all 4 freezing steps. PMID- 6265635 TI - Mesoionic xanthine analogues: phosphodiesterase inhibitory and hypotensive activity. AB - Several mesoionic thiazolo[3,2-alphapyrimidines and mesoionic 1,3,4 thiadiazol[3,2-alpha-pyrimidines were evaluated as inhibitors of cyclic-AMP phosphodiesterase. While small alkyl substituents at the 6 position have no significant effect on activity, phenyl and benzyl substituents enhance activity. Mesoionic structures such as 1 (R2 = H; R8 = Et) possess 20 to 40 times the activity of theophylline when the R6 substituent is phenyl or 4-chlorobenzyl. methyl and ethyl substitution at the 2 position essentially abolishes activity. Although plagued by solubility problems, several of the mesoionic derivatives were found to display weak hypotensive effects in vivo. PMID- 6265636 TI - Synthesis and antiherpetic activity of some 4-[(aryloxy)alkyl]pyrazoles. PMID- 6265637 TI - Pyrimidine acyclic nucleosides, 1-[(2-Hydroxyethoxy)methyl]pyrimidines as candidate antivirals. AB - A number of pyrimidine acyclic nucleosides were synthesized and tested for activity against herpes simplex virus type 1. Synthesis of 1-[(2 hydroxyethoxy)methyl]cytosine (8) and 1-[(2-hydroxyethoxy)methyl]uracil (14) was accomplished in two or three steps from 2,4-diethoxypyrimidine and 2 (benzoyloxy)ethoxymethyl chloride. The 5-methyl (20), 5-(trifluoromethyl) (21), and 5-fluoro (22) analogues of 14 were available in two steps form the appropriate bis(trimethylsilyl)ated 5-substituted uracil and 2 (acetoxymethoxy)ethyl acetate or 2-(benzoyloxy)ethoxymethyl chloride. Bromination of 8 and 14 or iodination of 14 gave the 5-halogeno-1-[(2 hydroxyethoxy)methyl]pyrimidines 9, 23, and 24. These pyrimidine acyclic nucleosides exhibited little or no activity against herpes simplex virus type 1 or against a range of other DNA and RNA viruses. This is compatible with their lack of substrate properties toward herpes simplex virus induced thymidine kinase. PMID- 6265638 TI - Synthesis and antiviral properties of (Z)-5-(2-bromovinyl)-2'-deoxyuridine. AB - (Z)-5-(2-Bromovinyl)uracil was obtained by photoisomerization of the E. isomer. Similarly, (E)-5-(2-bromovinyl)-2'-deoxyuridine gave the required Z isomer. (Z)-5 (2-Bromovinyl)-2'-deoxyuridine is much less active against herpes simplex virus type 1 (HSV-1) and somewhat less active against herpes simplex virus type 2 than is the E isomer. Both isomers show similar activity against vaccinia virus. Therefore, the highly potent and selective activity of (E)-5-(2-bromovinyl)-2' deoxyuridine against HSV-1 is due to its E configuration. PMID- 6265639 TI - Benz-fused mesoionic xanthine analogues as inhibitors of cyclic-AMP phosphodiesterase. PMID- 6265642 TI - Cerebral thrombosis, platelet aggregation and viral infection. PMID- 6265641 TI - Noise analysis of the K+ current through the apical membrane of Necturus gallbladder. AB - Current noise power spectra of the voltage-clamped (V = 0) Necturus gallbladder, exposed to NaCl-Ringer's on both sides contained a relaxation noise component, which overlapped with a 1/f alpha noise component, with alpha being about 2. Substitution of all Na+ by K+ on either the serosal or mucosal side increased the relaxation as well as the 1/f alpha noise component considerably. In Necturus gallbladder both noise components are reduced by addition of 10mM 2,4,6 triaminopyrimidine (TAP) or 5 mM of tetraethylammonium (TEA+) added to ification of the mucosal solution to pH 5 and lower. Five mM of tetraethylammonium (TEA+) added to the mucosal solution, abolished K+ relaxation noise and decreased the 1/f alpha noise component. Applying a Cs+ concentration gradient across the epithelium did not yield relaxation noise. However, if Rb+ was substituted for all Na+ on one side, a Lorentzian noise component appeared in the spectrum. Its plateau was smaller than with KCl-Ringer's on the respective side. These data confirm the existence of fluctuating K+ channels in the apical membrane of the Necturus gallbladder. Furthermore it can be concluded that these channels have a permeability sequence K+ greater than Rb+ greater than Cs+. The inhibition of the fluctuations by mucosal acidification indicates the existence of acidic sites in the channel. The single-channel conductance was estimated to be between 6.5 and 40 pS. PMID- 6265643 TI - Organization of chimeras between filamentous bacteriophage f1 and plasmid pSC101. PMID- 6265644 TI - Deoxyribonuclease II as a probe for chromatin structure. I. Location of cleavage sites. PMID- 6265645 TI - Transposon mutagenesis of the gene encoding the bacteriophage P1 restriction endonuclease. Co-linearity of the gene and gene product. PMID- 6265646 TI - Cleavage and methylation of DNA by the restriction endonuclease HinfIII isolated from Haemophilus influenzae Rf. PMID- 6265640 TI - Reconstitution of "carriers" in artificial membranes. PMID- 6265647 TI - Role of ATP in the cleavage mechanism of the EcoP15 restriction endonuclease. PMID- 6265648 TI - Studies on cobalt myoglobins and hemoglobins, XIII. A consequence of the occurrence of glutamine at the E7 (58) site of alpha subunits in opossum hemoglobin. PMID- 6265649 TI - Catalysis of accurate poly(C)-directed synthesis of 3'-5'-linked oligoguanylates by Zn2+. PMID- 6265650 TI - Template-directed synthesis of oligoguanylates in the presence of metal ions. PMID- 6265651 TI - p2H dependence of the exchange with the solvent of interior amide protons in basic pancreatic trypsin inhibitor modified by reduction of the disulfide bone 14 -38. PMID- 6265652 TI - Induction of slow action potentials by microiontophoresis of cyclic AMP into heart cells. PMID- 6265653 TI - Bone scanning in the detection of occult fractures. AB - The potential role of bone scanning in the early detection of occult fractures following acute trauma was investigated. Technetium 99m pyrophosphate bone scans were obtained in patients with major clinical findings (e.g., pain, swelling, tenderness) and negative or equivocal roentgenograms following trauma. Bone scanning facilitated the prompt diagnosis of occult fractures in the hip, knee, wrist, ribs and costochondral junctions, sternum, vertebrae, sacrum, and coccyx. Several illustrative cases are presented. Roentgenographic confirmation occurred following a delay of days to weeks and, in some instances, the roentgenographic findings were subtle and could be easily overlooked. This study demonstrates bone scanning to be invaluable and definitive in the prompt detection of occult fractures. PMID- 6265654 TI - The effects of follicle-stimulating hormone (FSH) on Sertoli cell junctions in vitro: a freeze-fracture study. PMID- 6265655 TI - Unilateral testicular enlargement resulting from inapparent 21-hydroxylase deficiency. AB - We report a case in which unilateral testicular enlargement was the only presenting sign in 21-hydroxylase deficiency of the "acquired" or adult onset type. Measurement of plasma 17-hydroxyprogesterone throughout 24 hours revealed marked elevations, mostly between 0400 and 0700 hours. However, this steroid increased more than 18-fold 30 minutes following adrenocorticotropic hormone administration, confirming the diagnosis. Glucocorticoid therapy corrected the testicular enlargement. Inapparent 21-hydroxylase deficiency is a medically treatable cause of testicular enlargement that can be diagnosed by measurement of plasma 17-hydroxyprogesterone during a 30-minute adrenocorticotropic hormone stimulation test. PMID- 6265656 TI - Signet ring adenocarcinoma of the prostate. PMID- 6265657 TI - Defining renal anatomy and function with 99mtechnetium dimercaptosuccinic acid: clinical and renographic correlation. PMID- 6265658 TI - Avian pox in buzzard (Accipiter nisus) in Iraq. PMID- 6265659 TI - Prevalence of selected pathogenic microbial agents in the red fox (Vulpes fulva) and gray fox (Urocyon cinereoargenteus) of southwestern Wisconsin. AB - Free-ranging red foxes (Vulpes fulva) and gray foxes (Urocyon cinereoargenteus) were trapped in southwestern Wisconsin. Fox sera were tested to determine the prevalence of antibody for five different Leptospira interrogans serovars, canine distemper virus (CDV), infectious canine hepatitis virus (ICHV), and Franciscella tularensis infections. Grippotyphosa was the most prevalent leptospiral serovar antibody observed. Twenty-five of 53 (47%) red foxes and 11 of 36 (31%) gray foxes had specific antibodies to grippotyphosa. Juvenile foxes had geometric mean antibody titers to grippotyphosa significantly higher (P less than 0.05) than those of the adults of both species. CDV antibody was detected in sera of red foxes only. Six of 57 (11%) red foxes had CDV antibody. ICHV antibody was detected in 2 of 57 (3%) red foxes and 3 of 32 (9%) gray foxes. Antibody to F. tularensis was not detected in any fox sera. PMID- 6265660 TI - Serratia endocarditis in a pediatric burn patient. Cure with cefotaxime. PMID- 6265661 TI - [Application of nuclear medicine to the diagnosis of myocardial infarct]. PMID- 6265662 TI - [Action mechanism and resistance of drugs used in visceral mycoses]. PMID- 6265663 TI - [4 cases of primary liver neoplasms---with special reference to the use of endoscopic retrograde cholangiopancreatography]. PMID- 6265664 TI - [Abnormal glucose metabolism--paraneoplastic syndromes--statistics and etiological mechanism]. PMID- 6265665 TI - [Abnormal lipid metabolism--paraneoplastic syndromes---statistics and etiological mechanism]. PMID- 6265666 TI - [Carcinomatous neuromyopathy--report of 2 cases]. PMID- 6265667 TI - [Polypeptide hormones as tumor marker]. PMID- 6265668 TI - [Electrophoretic separation of LDH isoenzymes using pyrophosphate buffer and agarose (author's transl)]. PMID- 6265669 TI - [Prostaglandin E2 in the rat gastric mucosa (3rd report) --effect of cimetidine (author's transl)]. PMID- 6265670 TI - [Clinicopathological studies of ultrasonogram in small hepatocellular carcinoma (author's transl)]. PMID- 6265671 TI - [A case of omental malignant fibrous histiocytoma (author's transl)]. PMID- 6265672 TI - [A study on endocrine disorders in patients with chronic renal failure (author's transl)]. PMID- 6265673 TI - [Aftercare of post-colostomy patients at the ambulatory clinic--ambulatory care of colostomy patients]. PMID- 6265674 TI - [Case conference: significance and overview of ambulatory care of colostomy patients]. PMID- 6265676 TI - Lack of parallelism between the positive inotropic effects of various cardiac stimulants and their activities to produce the slow channels in the depolarized myocardium. AB - Positive inotropic actions in the normal guinea pig cardiac muscle and the activities required to produce electrical and mechanical responses in the depolarized muscle were examined using epinephrine, dopamine, metanephrine, aminophylline, histamine, serotonin, tyramine, tetraethylammonium (TEA), tetramethylammonium (TMA), and X-537A, a calcium ionophore. In the normal cardiac muscle, histamine produced the greatest positive inotropic action, followed by epinephrine, dopamine and TEA. In the cardiac muscle made inexcitable by the elevated potassium (30 mM), all of the agents tested produced electrical and mechanical responses. Aminophylline was the most potent in the activity to produce the mechanical response in the depolarized muscle; the potencies of histamine, dopamine, X-537A, epinephrine and TEA were much the same. From these results, it was concluded that the positive inotropic effects of the cardiac stimulants are not produced solely through the mechanisms related to the slow channels, but that other mechanisms must be involved in the normal condition where the fast sodium channels are functioning. PMID- 6265675 TI - Carbon tetrachloride-induced loss of microsomal glucose 6-phosphatase and cytochrome P-450 in vitro. AB - Rat liver microsomes were incubated in the presence of NADPH and CCl4 under various conditions, and losses of glucose 6-phosphatase (G-6-Pase) and cytochrome P-450 were examined in terms of lipid peroxidation and CCl4 metabolism. Loss of G 6-Pase activity correlated well with the enhancement of lipid peroxidation. Loss of cytochrome P-450 was also dependent on the lipid peroxidation, under aerobic conditions. However, the cytochrome was destroyed under anaerobic conditions in which lipid peroxidation and loss of G-6-Pase were greatly suppressed. This anaerobic loss of cytochrome P-450 may be linked with the metabolism of CCl4 by this hemoprotein, as evidenced by the observation that CCl4 metabolism occurred only under anaerobic conditions and was inhibited by carbon monoxide accompanied by the suppression of the loss of cytochrome P-450. PMID- 6265677 TI - [Biochemical changes after parathyroidectomy in primary hyperparathyroidism. I. Serial changes of Ca, Mg,P, immunoreactive PTH and nephrogenous c-AMP during 2 weeks after parathyroidectomy (author's transl)]. PMID- 6265678 TI - In vivo antigenic modification of tumor cells. III. Metastatic thymic lymphoma specifically infected by thymotropic retrovirus. AB - Tissue distribution of radiation leukemia virus (RadLV) was examined after its inoculation into normal C57BL/6J (B6) mice, B6 mice bearing a transplantable, non virus-producing thymic lymphoma (RL12-NP), and B6 mice bearing a transplanted non virus producing, Harvey murine sarcoma virus-transformed fibrosarcoma. Virus expression was determined by competition radioimmunoassay for murine leukemia virus (MuLV) p30 (predominant group-reactive antigen of MuLV) and for RadLV p12 (a highly type-specific MuLV polypeptide) and by membrane immunofluorescence for cell surface gp71 (predominant envelope glycoprotein of MuLV). Normal adult B6 mice were given three sequential iv injections of RadLV and were examined several times up to 200 days later for the appearance of neoplastic disease or expression of virion antigens. No clinical abnormalities were noted, and animals remained healthy for greater than 200 days. Significant levels of MuLV p30 and RadLV p12 were detected only in the thymuses. Organs and tumors from RL12-NP-inoculated animals contained low or nondetectable levels of virion antigens. Inoculation of mice with RL12-Rad, a cell line derived by in vitro infection of RL12-NP cells with RadLV, produced widespread, discrete metastatic tumors and infiltrated the lymphoid organs of B6 mice in a pattern identical to that observed after administration of RL12-NP cells. Lymphoid organs of RL12-Rad-inoculated animals expressed variable levels of virion antigens reflecting differences in the extent of tumor cell infiltration as opposed to virus spread from tumor to host cells. Administration of infectious RadLV systemically into RL12-NP tumor-bearing animals converted these tumors to viron antigen expressors with levels in superinfected tumors equivalent to those found in RL12-Rad-induced tumors. Infection was highly selective, and host tissues were minimally contaminated by the inoculated virus. Part of this selectivity was explained by the thymotropic property of RadLV. A rapidly dividing murine fibrosarcoma was not infected by RadLV, but this same non-virus-expressing tumor could be infected by common fibrotropic MuLV isolates. PMID- 6265679 TI - Lack of Thy 1.2 antigen expression on the surfaces of mouse mammary epithelial cells. AB - Monoclonal antisera against mouse Thy 1.2 antigen were used to assess the expression of Thy 1.2 antigen on BALB/c and BALB/cfC3H normal mouse mammary gland epithelial cells (MMEC) and on spontaneous and transplanted BALB/cfC3H mammary adenocarcinoma cells. Immunofluorescence (IF) assays with the monoclonal anti-Thy 1.2 sera demonstrated that Thy 1.2 antigen was not expressed on the surface membranes of MMEC (both virus-free BALB/c and virus-infected BALB/cfC3H) and tumor (BALB/cfC3H) mammary epithelial cells. A specific antiserum against MMEC was used to establish the expression of this normal antigen(s) on the surfaces of both MMEC and tumor mammary epithelial cells obtained from virus-free and virus infected mice. In addition, the expression of the mammary tumor virus envelope glycoprotein gp52 was determined by indirect IF on the surfaces of virus-infected mammary epithelial cells, both MMEC and tumor cells. PMID- 6265680 TI - Murine mammary tumor virus seroepidemiology in BALB/cfC3H mice: correlation with tumor development. AB - Serum reactivity to murine mammary tumor virus (MuMTV) was inversely related to mammary tumor risk in 8-to 22-week-old BALB/cfC3H breeding females. Mice at low tumor risk exhibited high-titered serum reactivity to MuMTV (50% end point, greater than or equal to 1:40 by radioimmunoassay) approximately 3-6 months earlier than did the mice at high tumor risk. Maternal MuMTV antibody levels were correlated with the serum anti-MuMTV reactivity of their neonatal offspring (2 wk of age). Serologic antiviral reactivity in infected mice did not change during periods of pregnancy and lactation. All infected animals had detectable serum MuMTV reactivity by 33 weeks of age. The virus-neutralizing capabilities of some of these sera were tested, Sera from some of the young, low-tumor-risk animals that had MuMTV-precipitating antibodies also had virus-neutralizing activity. Conversely, none of the sera from the high-tumor-risk animals had detectable MuMTV-neutralizing antibodies. PMID- 6265681 TI - Colonies formed in agar from human breast cancer and their identification as T lymphocytes. AB - Single cell suspensions prepared from human breast cancer specimens by collagenase digestion were cultured in soft agar with phytohemagglutinin stimulated human lymphocyte-conditioned medium (PHA-LCM). In 6 of 10 different tumors, PHA-LCM-dependent clonal growth was develop. After 12-14 days of incubation, two morphologic types of colony containing 20-500 cells were recognized. Both were composed of lymphocytes of T-cell nature, as judged by cell morphology in smears, cytochemical properties, capacity to form rosettes with sheep erythrocytes, and electron microscopic appearances. Contamination of the tumor cell suspensions by blood could be excluded as a source of the colony forming lymphocytes, and the incidence of colony-forming cells correlated well with the degree of lymphocyte infiltration of the tumors. Some of the colonies in agar were expanded further in liquid culture in the continuous presence of PHA LCM. These clones were apparently high in proliferating capacity as compared with the proliferating activity of peripheral T-cell clones obtained from normal blood. These clones were considered to be highly activated T-lymphocytes and to be stimulated to grow in vitro by the T-cell growth factor contained in PHA-LCM. The direct cloning and expansion of such activated T-lymphocytes infiltrating the tumors will be useful for studies on the functional characteristics of these cells. PMID- 6265682 TI - Role of hormones in the growth and regression of human breast cancer cells (MCF 7) transplanted into athymic nude mice. AB - The hormonal environments require by human breast cancer cells MCF-7 to produce solid tumors in nude mice are described. A 100% take was obtained within 7 days following inoculation of 2X10(6) actively growing (log phase) MCF-7 cells into the mammary fat pads of intact, athymic BALB/c nude mice. Tumors failed to develop, even with an inoculum of 20X10(6) cells/mouse, in ovariectomized mice or in mice made diabetic with streptozotocin and observed for 90 days after cell inoculation. A 100% incidence of tumors was obtained in mice that were either hypophysectomized or made diabetic but received injections of 0.2 IU insulin/day/mouse. A 100% incidence of tumors was also obtained in ovariectomized mice that received 17 beta-estradiol in the form of a pellet placed subcutaneously in the interscapular region at the time of cell inoculation. Palpable tumors also developed in ovariectomized mice treated with prolactin, perphenazine, estrone, or estriol, but no takes were observed in ovariectomized mice treated with progesterone, 5 alpha-dihydrotestosterone, or hydrocortisone. Growth of the MCF-7 tumor was stimulated five- to sixfold in both intact and hypophysectomized mice that each received a 17 beta-estradiol pellet. Removal of the 17 beta-estradiol pellets form tumor-bearing ovariectomized mice failed to induce tumor regression. Tumors that continued to grow in ovariectomized mice deprived of 17 beta-estradiol regressed by 50% or more of their initial volume when tamoxifen was injected for 7 days at 5 micrograms/mouse/day) +/- theophyline (1 mg/mouse/day), tumor growth arrest was observed during the 2-to 3-week treatment period. Streptozotocin-induced diabetes in tumor-bearing mice always resulted in complete tumor regression following a 3-week treatment period. PMID- 6265683 TI - Cellular retinoic acid-binding protein in human lung carcinomas. AB - Cellular retinoic acid-binding protein (CRABP) was detected in the cytosol of 11 human non-small-cell lung cancer specimens. Neither normal lung nor a small-cell lung cancer specimen contained this binding protein. The quality of CRABP per milligram of cytosol protein ranged from 48.3 to 426.5 fmol. PMID- 6265684 TI - Fibrin clot retraction in normal and transformed avian fibroblasts. AB - Normal avian embryo fibroblasts induced retraction of a fibrin clot. The expression of high levels of this activity was associated with the exponential growth phase of the cell division cycle. Cells transformed by avian sarcoma virus (ASV) and other agents lost this activity regardless of the cell cycle phase. Cultures infected with transformation-defective ASV mutants retained a high level of fibrin clot retraction. However, this activity could not be recovered when temperature-sensitive, virus-transformed cells were shifted to a nonpermissive temperature (41 degrees C). The results indicated that, in this cell system, loss of fibrin clot retraction could be considered a reliable parameter of cell transformation. PMID- 6265685 TI - Cyproheptadine in the control of Cushing's disease. AB - A patient with Cushing's disease was treated with cyproheptadine with concomitant remission of the disease for 60 months. Despite clinical improvement and achievement of normal levels of cortisol excretions, her menstruation-related cyclic surge of cortisol secretion was supranormal. The mode of action of cyproheptadine was studied by the administration of metyrapone. Long-term administration of cyproheptadine appeared to normalize excessive adrenocorticotropic hormone (ACTH) production by reducing the frequency and the peak levels of episodic secretion of ACTH. PMID- 6265686 TI - [Benign glomus tumor of the stomach simulating a pancreatic cyst]. PMID- 6265687 TI - [Giant malignant fibroadenoma phyllodes of the breast]. PMID- 6265688 TI - [Surgical treatment results in chondromatosis of the joints]. PMID- 6265690 TI - [Who are we, what will we become?]. PMID- 6265691 TI - [Swiss Nurses' Association. Definition of the profession of registered male and female nurses]. PMID- 6265692 TI - [Propositions on the basic concerns of the caring professions]. PMID- 6265689 TI - [Approaches to a selective chemotherapy of hepatocellular carcinoma (author's transl)]. AB - 1. An improvement of the chemotherapy of hepatocellular carcinoma with adriamycin or 5-fluorouracil and a reduction of side effects has been achieved by intra arterial administration of the drugs. This treatment provides a somewhat extended survival but no cure. 2. The treatment of hepatocellular carcinoma in patients by reduction of an inactive precursor of a cytocidal alkylating agent by azoreductase of the tumor showed no therapeutic effect. 3. A selective hepatocellular uptake of drugs coupled to asialoglycoproteins has been described. An application of this concept for the chemotherapy of hepatocellular carcinoma seems doubtful since a loss of binding proteins for desialylated glycoproteins during experimental hepatocarcinogenesis has been demonstrated. 4. The increased uptake of 5-fluorouridine in hepatomas after induction of a tissue-specific depletion of uridine 5'-triphosphate and cytidine 5'-triphosphate provides an effective experimental chemotherapy with limited side effects. A clinical use of this new concept for the chemotherapy of hepatocellular carcinoma may serve as a useful approach. PMID- 6265693 TI - [Disquiet in nursing]. PMID- 6265694 TI - [Of interest to community nurses: subsidy for relatives in the Basel-City District]. PMID- 6265695 TI - [Current findings on the pathogenesis of multiple sclerosis]. PMID- 6265697 TI - [Ecotopia: the land of ecological utopia]. PMID- 6265696 TI - [A nurse becomes a patient ombudsman. Interview by Danielle Plerquin]. PMID- 6265698 TI - [Solidarity in nursing care]. PMID- 6265699 TI - [Health system, health policy]. PMID- 6265700 TI - [Hospital and students]. PMID- 6265701 TI - [The wishes of the patient]. PMID- 6265702 TI - Reye's syndrome simulacra in liver of mice after treatment with chemical agents and encephalomyocarditis virus. AB - In children with Reye's syndrome, liver specimens exhibit the following characteristics: mitochondrial dysfiguration, fatty infiltration, decreased activity of carbamyl phosphate synthetase and of ornithine transcarbamylase, histochemically reduced activity of succinic dehydrogenase and cytochrome oxidase, and depletion of glycogen. We intended to create an animal model for Reye's syndrome by treating mice with encephalomyocarditis virus, and/or salicylate, fructose, Atlox, butylated hydroxytoluene, pentachlorophenol, and an equal mixture of butylated hydroxytoluene and monosodium stearate. Liver specimens were then examined for the listed characteristics as well as for the activity of argininosuccinic lyase, arginase, phosphorylase, and glucose-6 phosphatase. Results of interest in regard to the experimental intention were obtained in livers of mice treated with virus and Atlox (A) or virus and butylated hydroxytoluene (B). In these specimens, we found a significant reduction (p less than 0.05)--except for ornithine transcarbamylase (A)--to the following levels (in percentage of normal mean): carbamyl phosphate synthetase (A, 79 per cent; B, 57 per cent); ornithine transcarbamylase (A, 91 per cent; B, 75 per cent); glycogen (A, 26 per cent; B, 37 per cent). Simultaneous morphologic analysis of these liver specimens indicated mitochondrial dysfiguration, absence of dense granules, fatty infiltration, and normal activity of succinic dehydrogenase and cytochrome oxidase. The induction of Reye's syndrome-like features in mouse liver may be useful for the study of disease mechanisms and therapy. PMID- 6265703 TI - The deformity of thumb in ulnar paralysis. AB - The flexion/extension angles at the Metacarpophalangeal and Interphalangeal joints of the thumb in position of rest and pinch were studied in 68 thumbs of ulnar paralysis. In two thumbs the flexor pollicis brevis was not paralysed. Twenty five normal thumbs were used as controls for comparison. During the resting position the metacarpophalangeal joints showed less flexion and interphalangeal joints more flexion than normal. During the pinch position metacarpophalangeal hyperextension and interphalangeal flexion -- the Z deformity was seen in about 60% while marked interphalangeal flexion was seen in all thumbs of ulnar paralysis. It is suggested that this muscular imbalance is likely to affect thumb joints in time because of abnormal stresses due to altered forces and this can be prevented by restoring the muscle balance by surgery. PMID- 6265705 TI - Interaction of serum and cell spreading affects the growth of neoplastic and non neoplastic fibroblasts. AB - Both growth factor availability and cell-to-cell contact have been mechanisms used to explain cell growth regulation at high cell density. Recently Folkman and colleagues have shown that changes in cell shape, rather than cell-to-cell contact, can regulate the growth of fibroblasts. However, in those studies the relation between serum and shape regulation of growth was not studied, nor were neoplastic and non-neoplastic cells compared. In this report we have studied these aspects by varying cell spreading and serum concentration independently for 2 non-neoplastic and 3 neoplastic cell lines. Cell spreading (projected cell area) was controlled by decreasing the adhesiveness of tissue culture growth was measured as the increase in cell number/day. We have found that more spreading increased net growth of both neoplastic and non-neoplastic cells, while less spreading (toward rounded configuration) depressed growth. There were also quantitative differences between neoplastic and non-neoplastic cells. Neoplastic cells continued to grow under conditions of cell rounding, which completely prevented the growth of their non-neoplastic counterparts. Some neoplastic cells also tended to show little or no increase in net cell number for serum concentrations above 10% as cells became more spread; in contrast, all non neoplastic cells grew more with increasing concentrations of serum as they became well spread. Thus, in normal cells, it appears that the sensitivity of cells to humoral factors is governed by cell spreading. This interaction between serum and cell shape is less prominent in some neoplastic cells. PMID- 6265704 TI - Proteolytic domains of the epidermal growth factor receptor of human placenta. AB - Microsomal membranes form human placenta, which bind 5-20 pmol of 125I-epidermal growth factor (EGF) per mg protein, have been affinity-labeled with 125I-EGF either spontaneously or with dimethylsuberimidate. Coomassie blue staining patterns on SDS polyacrylamide gels are minimally altered, and the EGF-receptor complex appears as a specifically labeled band of 180,000 daltons which is not removed by urea, neutral buffers, or chaotropic salts but is partially extracted by mild detergents. Limited proteolysis by alpha chymotrypsin and several other serine proteases yields labeled fragments of 170,000, 130,000, 85,000, and 48,000 daltons. More facile cleavage by papain or bromelain rapidly degrades the hormone receptor complex to smaller labeled fragments of about 35,000 and 25,000 daltons. These fragments retain the binding site for EGF, are capable of binding EGF, and remain associated with the membrane. Alpha chymotryptic digestion of receptor solubilized by detergents yields the same fragments obtained with intact vesicles, suggesting that the fragments may represent intrinsic proteolytic domains of the receptor. PMID- 6265706 TI - Alterations in growth requirements of kidney epithelial cells in defined medium associated with malignant transformation. AB - The possibility has been investigated that 1) the supplements required for the growth of the Madin Darby Canine Kidney (MDCK) cell line in serum-free Medium K-1 are indeed requirements for the growth of normal kidney cells in vitro, and 2) that alterations in these growth requirements are associated with malignant transformation. Consistent with the hypothesis that MDCK cells resemble normal kidney cells in culture, primary cultures of baby mouse kidney epithelial cells grow in Medium K-1 and respond to the 5 components in the medium. The growth properties of Moloney sarcoma virus (MSV)-transformed MDCK cells in defined media have been examined. Unlike MDCK cells, MSV-transformed MDCK cells form tumors in adult nude mice. Although they still respond to the 5 factors in Medium K1, the optimal dosage for insulin is lower for the MSV transformants than for MDCK cells. The MSV transformants also have an additional requirement for growth in Medium K-1-fibronectin. Variants of MDCK cells have been isolated that have lost the PGE1 requirement for growth in defined medium. These variant cells have acquired 1) the ability to form tumors in adult nude mice and 2) an alteration affecting cAMP metabolism, in addition to PGE1 independence. PMID- 6265707 TI - Herpes simplex type 2 neutralization antibodies in patients with cancers of urinary bladder, prostate, and cervix. AB - In the blood samples obtained from a total of 68 patients with cancers of the urinary bladder, prostate, and cervix, who applied to the Departments of Urology, Obstetrics, and Gynecology of Hacettepe Medical Faculty, neutralizing antibodies were sought for against herpes simplex type 2 by neutralization test. The same test was applied to 35 control patients with no known malignancies. In contrast to the presence of the antibody in 62.86% of the control subjects, this ratio was 90.70% in patients with cancer of the urinary bladder, 87.50% in those with prostatic carcinoma, and 88.89% in those with cancer of the cervix. PMID- 6265709 TI - Analysis of gated flux from or into sealed membrane fragments. PMID- 6265708 TI - Familial bilateral breast cancer. AB - The occurrence of bilateral breast cancers in three members of one family is reported. In two members, evidence of a distinct primary lesion in each breast was verified. The occurrence of unilateral breast cancer and other cancers in other members of the family was surveyed. Recommendations for early detection and surveillance in familial breast cancer at the present time should be aggressive and close follow-up of the affected members. Absence of reliable markers preclude effective surveillance for early detection or susceptibility. PMID- 6265710 TI - A new current expression for selective ion permeation across membranes. PMID- 6265711 TI - Sex and polymorphism as strategies in host-pathogen interactions. PMID- 6265712 TI - Improved myocardial protection with nifedipine and potassium-based cardioplegia. AB - Thirty dogs were studied acutely on cardiopulmonary bypass in four groups. Hearts in Groups 1C (standard cardioplegia, n = 5) and 2c (n = 10) were subjected to periods of global ischemia of 1 and 2 hours, respectively. Both groups received 300 cc boluses of hypothermic (4 degrees C), potassium-based cardioplegic solution infused via an 18 gauge needle proximal to the aortic cross-clamp, at every 30 minute interval of ischemia. Groups 1CN (standard cardioplegia plus nifedipine, n = 5) and 2CN (n = 10) were treated similarly, except that nifedipine (5 microgram/kg) was added to each 300 cc bolus of cardioplegic solution. The addition of nifedipine in Groups 1CN and 2CN resulted in statistically significant reduction in myocardial water content (p less than 0.005), mean left atrial pressure (MLAP) (p less than 0.05), and myocardial compliance (p less than 0.005) as compared to the control groups (1C and 2C). Recovery of left ventricular dp/dt in Experimental Group 2CN was also statistically better (p less than 0.025) than in Control Group 2C. Examination of myocardial biopsy tissue by electron microscopy was not conclusive. Nifedipine used in combination with hypothermic, potassium-based cardioplegia provided significant additional myocardial protection over cardioplegia alone. PMID- 6265713 TI - Use of the single electrode voltage clamp to perform noise and relaxation studies of acetylcholine-activated channels in Aplysia neurons. AB - The single electrode voltage clamp has been used to perform fluctuation analysis ("noise" analysis) and relaxation experiments in order to study the average lifetime and conductance of ACh-activated sodium channels in Aplysia neurons. Measured values of average channel lifetime, which is approximately 20 msec at - 80 mV and 11 degrees C, and elementary conductance, which is approximately 8 pS, are consistent with previously published results using two electrode clamping. The frequency response of the clamp was evaluated to determine its capabilities and limitations for the study of membrane currents. Sinusoidal currents injected into a voltage-clamped model membrane to simulate the frequency components of membrane noise are accurately reproduced at frequencies up to 500 Hz. Following a voltage clamp command, the new membrane potential is established in less than 2 msec, and current relaxations recorded after that time can be used to determine average channel lifetime. Since the frequency response of the clamp is much greater than the average lifetime of ACh-activated channels in Aplysia neurons, the single electrode voltage clamp is comparable to conventional two-electrode systems for investigating the properties of these channels, and may also be useful in other systems in which the time course of membrane currents is much slower than the frequency response of the clamp. PMID- 6265714 TI - Age-related changes of cyclic nucleotide levels in rat brain regions. AB - Cyclic AMP and cyclic GMP levels were measured in seven brain areas of rats 4-30 months old. In several brain areas cyclic nucleotides were higher in 4-month-old rats than in rats 12 months old or older. On the other hand, in the hypothalamus cyclic GMP levels were decreased only in 30-month-old rats, a pattern of onset similar to that of senile deterioration. PMID- 6265715 TI - Activation of promutagens by liver homogenates isolated from female mice at different ages; lack of significant differences. AB - Liver S-9 (9000 g supernatant) fractions isolated from 2-, 12- and 26-month untreated female Swiss-Webster mice were compared under different assay conditions as to their abilities to activate 2-acetylaminofluorene, benzo(a)pyrene, and dimethylnitrosamine to mutagens in Salmonella typhimurium tester strain TA 100. All fractions activated these compounds to mutagens, although 2-acetylaminofluorene was only weakly mutagenic. Some differences in the activating abilities of the three age groups were observed but they were for the most part relatively small. PMID- 6265716 TI - Age-associated decrease of adenylate cyclase activity in rat myocardium. AB - Myocardial inotropic and chronotropic responses to beta-adrenergic agonists are diminished with aging. Since myocardial beta-adrenergic receptors are unaltered with age, we tested the hypothesis that this decreased responsiveness is related to a defect in the adenylate cyclase system. Isoproterenol-stimulated adenylate cyclase activity was assessed in myocardial membranes from Fischer 344 rats of 3, 12, and 24 months of age. Basal, as well as F-, GTP-, and hormone-stimulated adenylate cyclase activity was decreased by 20-30% with age. The Km of the enzyme for ATP was not found to be statistically different for any age group studied. These data support the hypothesis that the diminished responsiveness seen in senescence is a result of an alteration in either the catalytic subunit or the coupling protein (N) of the adenylate cyclase complex. PMID- 6265717 TI - [Peripheral neuropathy and insulinoma (author's transl)]. AB - A case of insulinoma is reported with disease of the peripheral nervous system and pathological demonstration of a primary nerve lesion. On admission the female patient gave a history of hypoglycemic episodes and paresthesias and loss of strength in both hands. Physical examination disclosed loss of strength and atrophy of the distal musculature of the extremities, predominating in the upper ones and without fasciculations. Muscle biopsy demonstrated changes suggestive of neurogenous atrophy, and biopsy of the sural nerve showed reduction of the myelin fibers with axonal degeneration, important signs of demyelinization, and remyelinization figures. The neuropathy was unchanged two months after removal of the insulinoma. The exact location of the nerve lesion in insulinoma is controversial, some authors placing it in the peripheral nerve while others believe the motor neurons of the anterior horns to be diseased. The pathological findings in the present case suggest primary nerve disease, but an associated lesion of the anterior horns could also be present. PMID- 6265718 TI - [Treatment of gestational trophoblastic disease]. PMID- 6265719 TI - Clinical experience with cefotaxime (HR-756) in surgical patients. AB - Twenty adult surgical patients aged between 15 and 83 years (mean:45), 10 of whom had wound infections (one complicated with septicaemia), 2 with septicaemia, 1 with gynecological infection complicated with endocarditis, 5 with urinary tract infections and 2 with lower respiratory tract infections, were treated with parentally-administered cefotaxime. Aetiology was Proteus 7, E. coli 4, Pseudomonas 3, Enterobacter 2, Klebsiella 2 and 2 Serratia. Susceptibility testing was determined by the agar dilution method, with MIC values ranging from 0.01 to 5 microgram/ml, with two urinary isolates of Pseudomonas with MIC of 20 microgram/ml. Clinical responses were excellent in 13 (65 per cent) cases, moderate in 2 (10 per cent) and 3 (15 per cent) failed to respond to therapy. Clinical assessment was not possible in three patients. Bacteriological responses were excellent in 14 (70 per cent) cases, poor in 4 (20 per cent) and in two there was no follow-up. Systemic tolerance was good in all patients except one. PMID- 6265721 TI - Opioid activities of beta-casomorphins. PMID- 6265720 TI - [Clinical experience in a case of orthotopic liver transplantation by use of an atypical caval vein anastomosis (author's transl)]. AB - The two main indications for liver grafting are primary malignancy and parenchymatous liver disease. In both cases orthotopic transplantation remains the preferred technique. Since graft rejection was considered not to be the main problem in clinical liver transplantation, recent improved survival rates were reported to be due to a more aggressive diagnostic management and consequent treatment of postoperative complications nonrelated to graft rejection. Because of the limited number of organs available for organ grafting sometimes technical modifications may become necessary. This was the case in a 40-year old male patient suffering from primary malignant hepatoma. The donor was a child, and during operation a great difference between organ size and length and diameter of the hepatic vessels became evident. Orthotopic transplantation was performed using an unusual method of caval vein anastomosis. Initially the patient did very well, but later on liver function deteriorated and the patient died in the eighth postoperative week because of hepatic artery thrombosis. The autopsy showed that all other vascular anastomosis were patent and no signs of portal hypertension were evident. The surgical technique used in this case is described in detail and some interesting aspects are discussed. PMID- 6265722 TI - Effects of septic shock plasma on adrenocortical cell function. PMID- 6265723 TI - Binding of luteinizing hormone-releasing hormone analogues to dispersed rat pituitary cells. PMID- 6265724 TI - Intraventricular cholecystokinin-octapeptide produces hyperglycemia in rats. PMID- 6265725 TI - Decreased superoxide anion radical production by rat alveolar macrophages following inhalation of ozone or nitrogen dioxide. PMID- 6265727 TI - Presence of specific prolactin binding sites in the rabbit hypothalamus. PMID- 6265726 TI - Norharman inhibition of [3H]diazepam binding in mouse brain. PMID- 6265728 TI - Differential ontogeny of type 1 and type 2 benzodiazepine receptors. PMID- 6265729 TI - Effect of lyso-phosphatidylserine on rat hypothalamic cAMP, in vivo. PMID- 6265730 TI - Supersensitivity of substantia nigra pars reticulata neurons to GABAergic drugs after striatal lesions. PMID- 6265731 TI - Multiple opiate receptors in guinea-pig ileum. PMID- 6265732 TI - Behavioral and neurochemical effects of the new opioid peptide dynorphin--(1-13): comparison with other neuropeptides. PMID- 6265734 TI - [Cultural aspects of mental disorders in Ivory Coast (an ethnopsychiatric approach) (author's transl)]. AB - The authors recall first the presence social conditions in Ivory Coast. Then, they describe the main mental disorders they have observed and they compare and analyse their own diagnosis with reference to european and american patterns and to those given in Dakar by Collomb. Studying the etiologic problems, they consider the question of the ethnic originality of mental diseases, and, as a consequence of it, the value of african indigenous treatments. PMID- 6265733 TI - Phospholipid acyl group composition in normal and tumoral nerve cells in culture. AB - We have studied the fatty acid composition of total phosphoglycerides from various types of nerve cells in culture. Primary cell cultures were compared with tumoral cell strains. Glial cells exhibited no characteristic pattern when compared to neurons. Tumoral cell phosphoglycerides contained much higher levels of octadecenoic acid and lower levels of C-20 to C-22 polyunsaturated fatty acids than normal cell phosphoglycerides. This observation seems to be a general feature in tumoral cell membranes. It could be of interest in respect to the membrane fluidity of cancer cells. PMID- 6265735 TI - [Prevention of infection in abdominal surgery using cefotaxim]. PMID- 6265736 TI - Electron microscope study of the effect of benzalkonium, chlorhexidine and polymyxin on Pseudomonas cepacia. AB - Electron micrographs of Pseudomonas cepacia cell grown in nutrient broth show an external membrane which is distinctly wavy, when compared with similar preparations of Pseudomonas aeruginosa, and which is not affected by growing in the presence of broth containing benzalkonium (10 microgram/ml), chlorhexidine (10 microgram/ml) or polymyxin (25 units/ml). Both benzalkonium (10 microgram/ml) and chlorhexidine (10 microgram/ml) damage the cytoplasmic membrane of P. cepacia cell grown in the presence of the chemicals. Contrasts are shown between the effect of polymyxin (chlorhexidine and benzalkonium) on the outer membrane of P. cepacia and P. aeruginosa. PMID- 6265737 TI - Deconjugation of bile salts by Bacteroids and Clostridium. AB - Deconjugation of bile salts by four strains of Bacteroides and four strains of Clostridium was studied by use of resting cells and cell-free culture supernatants. Bacteroids strains yielded active cells but showed relatively low bile salt hydrolase (BSH) activity in the culture supernatants while the reverse was the case for the spore-forming clostridial strains. BSH was formed constitutively and was oxygen insensitive. The optimum pH was between 4.5 and 5.0. Marked substrate specificity was found in two strains, one Clostridium and one Bacteroides, which showed restricted activity against taurine conjugates. Bacteroides in general attacked the taurine conjugates of dihydroxy bile acids more readily than the trihydroxy taurine conjugates. Deconjugated bile acid moieties were further modified by some resting cells, depending on the bacterial strain while no enzymatic activity other than that of BSH was found in the culture supernatants. Cells of B. fragilis 2536 performed 7 alpha-dehydrogenation when the pH of the medium allowed the reaction, and this oxidative process was markedly enhanced in the presence of an abundant supply of oxygen as a terminal electron acceptor. C. perfringens PB 6K produced the 3- keto product in addition to the 3 beta-hydroxy derivative of the liberated bile acids and the formation of the latter derivative seemed to take place without preliminary deconjugation. PMID- 6265738 TI - Three phases in transformation of human lymphocytes by Epstein-Barr virus, as revealed by colony formation in soft agar. AB - Human cord lymphocytes were examined for colony formation in soft agar medium at various times after infection with Epstein-Barr virus (EBV). The transformation process could be divided into the following three sequential phases: (1) A pre early phase, lasting about 10 hr post infection (pi), during which the number of transformed colonies was virus dose dependent. (2) An early phase, between about 10 and 60 hr pi, during which cloning efficiency was markedly lower than that of the pre-early phase. (3) A later phase, starting at about 60 hr pi, during which cloning efficiency was restored and the number of colony formers increased in an exponential fashion. EBV-associated nuclear antigen-positive cells first appeared at the beginning (12 hr pi) of the early phase and increased continuously thereafter. Increased DNA synthesis began at about 48 hr pi. These results suggest that the cloning efficiency of the infected cells changes during the transformation process, possibly reflecting altered cell sensitivity to agar. PMID- 6265739 TI - Biological properties of plaque-size variants of Sendai virus. AB - Large (RL)-and small (RS)-plaque variants of Sendai virus were isolated in culture of LLCMK2 cells in the presence of trypsin and their biological properties were determined. The RL variant was more virulent to mice than the RS variant. The RL variant had a higher growth rate than the RS variant in multiple step growth in the presence of trypsin, but the two variants had an almost equal growth rate in its absence. Restoration of hemolytic activity in cleavage of the F protein of the RL variant were achieved by milder trypsin treatment than was needed for the RS variant. PMID- 6265740 TI - Requirement of carbohydrates for cell fusion induced by vesicular stomatitis virus. AB - The fusion of BHK-21-KB cells by vesicular stomatitis virus was not induced in Eagle's minimal essential medium without glucose. In medium containing glucose, the rate of polykaryocyte formation decreased as the concentration of glucose was reduced below 5 mM. However, no reduction in virus production 24 hr after infection was seen under this condition. Addition of pyruvate or mannose to the culture medium caused a reversal of cell fusing activity. Cell fusion and virus growth were significantly suppressed by sodium azide and 2,4-dinitrophenol. PMID- 6265741 TI - Clinical studies on cell-mediated immunity in gestational trophoblastic disease: nonspecific cellular immunocompetence in patients with hydatid mole and trophoblastic neoplasia. AB - The nonspecific cell-mediated immunocompetence of 51 patients with gestational trophoblastic disease (GTD), including 16 patients with hydatid mole (HM), 24 with nonmetastatic trophoblastic neoplasia (NTN) and 15 with metastatic TN (MTN), was studied with the use of both in vitro and in vivo parameters of cell-mediated immunity (CMI) such as lymphocyte blastogenic response to phytohemagglutinin (PHA), subpopulation constitution, and delayed cutaneous hypersensitivity responses to 2,4-dinitrochlorobenzene (DNCB) and to purified protein derivative of tuberculin (PPD). The pretreatment cell-mediated immune status of patients with HM developing no malignant sequelae was shown to be essentially similar, in terms of both in vitro PHA and in vivo DNCB reactivities, to that of normal women and of patients with benign gynecological diseases. In patients with TN, however, there was a significant depression in the blastogenic lymphocyte response to PHA before evacuation of the mole, which was persistently demonstrated after uterine evacuation and more marked throughout the course of disease in patients with MTN, than in those with NTN, with a tendency to return to normal in remission. Moreover, patients with TN had a significant depletion of T lymphocytes as determined by rosette-forming cell procedures before treatment, which was most evident in patients with MTN. Plasma from the MTN patients was also shown to have an inhibitory effect on PHA responsiveness of lymphocytes from normal women. There was an increased incidence of impaired reactivity to DNCB in patients with TN (higher in MTN than in NTN), compared with HM and benign diseases, while no such difference in incidence was observed in response to PPD. On the basis of these findings, a preliminary characterization of altered immunocompetence in patients with TN and its mechanism are discussed. PMID- 6265742 TI - [Effect of cations on elution of enteroviruses adsorbed on bentonite]. PMID- 6265743 TI - [Cytomorphological method of determining the infectious titer of SV40 virus]. PMID- 6265745 TI - Herpes virus. PMID- 6265744 TI - The use of cefotaxime in serious and problem surgical infections. PMID- 6265746 TI - Reactivity of antibodies in human serum with antigens of an enteropathogenic bovine coronavirus. AB - Antibodies in human serum against an enteropathogenic bovine coronavirus were detected by double immunodiffusion (DID), neutralization of infectivity, indirect immunofluorescence, and immune electron microscopy. Human sera reacting in the DID test neutralized the infectivity of the bovine coronaviruses to indices of 2.5 to greater than 5. Nineteen of 40 DID-negative, heat-inactivated sera had neutralizing indices of 1 to 3.0. Human serum with neutralizing and DID antibodies produced juxtanuclear and cytoplasmic fluorescence identical to that of bovine immune serum in cells infected with the bovine coronavirus. Antibodies in human and bovine sera interacted with the peplomeres of the bovine coronavirus, matting and bridging them, when present in excess, and facilitated formation of large viral aggregates when present in equivalent concentrations. Complement added to the virus-antibody complexes did not alter specifically the morphology of single, antibody-laden viral particles or viral particles in aggregates. Evidence of the transmission of coronavirus from experimentally inoculated calves to man, with ensuing gastroenteritis, was found by electron microscopic tracing of the coronavirus and its virus-antibody complexes. PMID- 6265747 TI - Polypeptides and major antigens of four new isolates of cytomegalovirus. AB - Two strains of cytomegalovirus (CMV) from patients with renal transplants and two other strains of CMV from young children were successfully propagated in human diploid cells, MRC5. Analysis by SDS-PAGE of these viruses passaged only 4 to 6 times revealed 21 to 29 polypeptides. The freshly isolated strains differed from reference strains, Ad 169 and Davis, in the number of bands, in the intensity of labeling of each band and also in molecular weight of the polypeptides. Some bands were common to all six strains. Some bands of molecular weight above 105 K were present in some strains and not in others. This was also the case for some bands between 64 and 76 K and two to five bands at low molecular weight between 17 and 22 K were detected. The band at 68 K was the most intensely labeled. Several polypeptides were precipitated by immune sera containing antibodies to CMV (one positive human serum and one guinea pig antiserum to Davis strain). Different bands were observed after precipitation, depending on the antiserum used and the strain of virus. Interstrain differences were found to be associated with antigenic heterogeneity. However, these cannot be correlated as yet with primary infection or reactivation. PMID- 6265749 TI - [Scintiscanning with 99mTc-pertechnetate in the detection of Meckel's diverticulum]. PMID- 6265748 TI - Differences in the morphology of herpes simplex virus infected cells. II. Type specific membrane alterations of HSV-1 and HSV-2 infected cells. AB - The two types of herpes simplex virus (HSV-1, HSV-2) induced significantly different alterations in the morphology and permeability of infected cells. HEp-2 cells infected with HSV-1 (strain THEA) were characterized by the formation of polynuclear syncytia. In contrast, after infection with HSV-2 (strain D316, DD), the cells were rounded up. The HSV-1 strains KOS and LS5039 and the HSV-2 strain 196 induced both types of cytopathic effect. As shown by comparative scanning and transmission electron microscopy newly synthesized virus particles of the various strains of HSV-1 were generally found to be restricted to smooth areas of the cell surface. In these areas the number of microvilli was reduced in comparison to uninfected cells. However, the progeny viruses of the strains of HSV-2 were mainly connected with protrusions of the cell membrane (microvilli and filopodia). The morphological changes in cells infected with either type of HSV were associated with different functional alterations of the cell membrane. The membranes of HEp-w cells became more stable after infection with HSV-1. This is characterized by a reduced permeability for 51Cr as well as by a decreased sensitivity to the detergent Triton-X-100. HSV-2 induced opposite effects on the stability of the membrane in infected cells. In contrast to these findings with HEp-2 cells, opposite results were obtained with primary chick embryo fibroblasts: Infection with HSV-1 rendered the cell membrane more permeable for 51Cr and a reduction of the 51Cr-release was achieved by infection with HSV-2. The results show that HSV-cell interactions depend on the type of the virus as well as on the type of the infected cell. PMID- 6265750 TI - [Survey of infantile tumors in siblings in Italy]. PMID- 6265751 TI - [Drugs and environmental pollutants in human milk]. PMID- 6265752 TI - Outbreak of illness due to Clostridium perfringens--California. PMID- 6265753 TI - Pneumocystis pneumonia--Los Angeles. PMID- 6265754 TI - Adrenal function testing in animals. PMID- 6265755 TI - Antitumoral action of bovine seminal ribonuclease. AB - The antitumor action of bovine seminal RNAase is studied as a function of the enzyme concentration and of the number of plated cells. With polyoma transformed hamster kidney cells, a 50% inhibition of cell growth is obtained with a 10 micrograms/ml of enzyme, while at this concentration growth of normal cells is very little affected. On the other hand the higher the number of plated cells, the lesser is the effect. The enzyme is found to be very effective also on tumor cells derived from a spontaneous tumor (neuroblastoma) and on cells derived from a chemically induced tumor (glioma). Amphoterycin B which is known to alter the permeability of eukariotic cells, does not affect the resistance of normal cells to the cytotoxic action of the enzyme. PMID- 6265756 TI - A model structure for Rous sarcoma virus genomic RNA and its implication for various functions of the viral RNA. PMID- 6265757 TI - Viral RNA content of bovine leukemia virus-infected cells. AB - A bovine leukemia virus (BLV)-producing cell line, fetal lamb kidney cells infected with BLV (FLK) contains one or a few copies of BLV proviral DNA in its genome. These cells contain 0.002% of viral RNA which sediments, in a sucrose gradient, at about 35S and between 18S and 28S. In cattle affected by enzootic bovine leukosis, tumor cells and circulating lymphocytes also contain one or a few copies of BLV proviral DNA integrated in their genome. However, in all cases tested (except one), no viral RNA was detected in these cells in conditions where one or two copies of viral genomic RNA per cell would have been easily detected. PMID- 6265759 TI - [Electron transfer in hemoproteins. VI. The dependence of the reduction rate of ferricytochrome c by oxymyoglobin on ionic strength]. AB - The rate of the redox-reaction between MbO2 and ferri-Cyt c has been investigated in the pH range 5-8 under different ionic strength of the solution. The influence of various anions-phosphate, chloride, sulfate and acetat on the rate of the reaction were also studied. It has been shown that under the low ionic strength, I less than 0.1, all pH-dependence curves have pronounced maximum near pH 6.0. While the ionic strength values increase in this interval the reaction rate falls markedly, the profile of lg k versus square root of I/1 + square root of I is linear. Under high ionic strength values, I greater than 0.1, the reaction rate in MbO2-Cyt c system is only slightly influenced by increasing salt concentrations and by pH changing. The results obtained support the idea that the local interactions of charged groups in " active sites" of MbO2 and Cyt c play the most important role in the mechanism of electron transfer. On the contrary net charges of the molecules have a negligible effect on the rate of the reaction. Compared to anions Cl-, SO42- and CH3COO- which influence the reaction rate in an analogous way, phosphate ions have essential inhibiting effect. This is most likely explained by the specific bonding of the phosphate ions to Cty c in the immediate vicinity from the site of the "active contact" with Mb molecule. PMID- 6265758 TI - Some features of nucleo-cytoplasmic RNA transport from isolated nuclei. AB - Messenger RNA is released preferentially from isolated rat liver nuclei in the presence of the ATP-generating system and cytosol. The release is suppressed by spermidine, while cytoplasmic RNase inhibitor was ineffective and PCMB like some other thiol-blocking agents inhibitory. Cytoplasmic SOD added to the system strongly suppressed RNA release. A similar effect could be obtained by anaerobiosis due to addition of SMP. In both cases the inhibition is reversed by cyanide. In contrast to normal liver where the generation of superoxide radicals takes place almost exclusively in microsomes and is coupled with the oxidation of NADPH, in mouse ascites hepatoma 22a the generation of superoxide radicals occurs mainly in the nuclear envelope and is coupled wih the oxidation of both NADPH and NADH and inhibited by cyanide. PMID- 6265760 TI - [Cloning fragments of bacteriophage T5 DNA, determining expression of phage dependent ligase]. AB - Cloning vector lambda gt-p MB9 has been used for cloning of DNA fragments of bacteriophage T5 produced by EcoR*I activity. One clone contains a DNA fragment of 2.2 Md which has been mapped at 67-71% on the physical map of the genome. Functional studies have shown that bacteriophage lambda gt-T5 can grow on E. coli lights 7. Infection of this E.coli strain with phage lambda gt-T5 induces DNA ligase activity which has been previously observed in E. Coli infected with bacteriophage T5. PMID- 6265761 TI - [Reaction of pyrophosphorolysis catalyzed by Escherichia coli RNA polymerase]. AB - E. coli RNA polymerase is shown to be capable of catalyzing consecutive DNA dependent pyrophosphorolysis of RNA in the presence of inorganic pyrophosphate and Mg2+. Active ternary complex of the enzyme with DNA and nascent RNA is needed for the reaction, the mixure of all the components can not carry out pyrophosphorolysis. The reaction was realized in the absence of added nucleoside triphosphates. Nucleoside triphosphates are low molecular mass products of the reaction. The rate of pyrophosphorolysis of the RNA synthesised for the AI promoter of the DNA of wild type T7 phage and delta D III T7 mutant phage was followed as a function of primary structure of the DNA, temperature, ionic strength and inorganic pyrophosphate concentration. The relative rate pyrophosphorolysis for particular nucleotides in different regions of the RNA can differ by several orders of magnitude depending on the primary structure of the RNA that undergoes pyrophosphorolysis. Ternary complex containing partially pyrophosphorilised RNA is active on the RNA synthesis when pyrophosphate is removed and nucleoside triphosphates are added to the reaction mixture. RNA as short as 70-8 nucleotides long can be produced at the conditions used. It seems that efficient dissociation in this region of RNA limits the pyrophosphorolysis to proceed up to the 5' end of RNA. Ternary complex of RNA polymerase with nascent RNA and DNA is shown to undergo site specific dissociation. The specificity of the dissociation is shown to be a function of the primary structure of RNA and the direction of the reaction. Dissociation occurs at different places along RNA sequence when the RNA is synthesised and when it is pyrophosphorilised. PMID- 6265762 TI - [Factors influencing the pulse character of RNA elongation in vitro by E. coli RNA polymerase]. AB - Pause location along primary structure of two RNA fragments each 200 nucleotide residues in the length synthesized from A1 promoters of T7 phage DNA and delta D111 T7 phage DNA was analyzed. No correlation between the location of pauses and GC-rich or self complementary regions of RNA were found. The location of pauses does not change upon the variation of the temperature or ionic strength. Concurrent variation of all four NTP concentrations also did not influence pausing pattern. However the distribution of pauses depends highly on the ratio of the individual substrate concentrations. Substitution of GTP by ITP changes the pausing pattern completely. Inorganic pyrophosphate (PPi) of inhibits RNA elongation preferentially in the regions: NAUN, CGUAG. The study of PPi action on RNA terminated with 3' OCH3-NMP suggest that the sequence-specific inhibition of RNA elongation may be a result of pyrophosphorolysis of terminal nucleotide residues of RNA. It was proposed that the pulse character of RNA elongation stems rather from differences in the kinetic constants of nucleotides attachment and pyrophosphorolysis from the 3'-termini of RNA than by termination signals encoded in the primary structure of DNA. The stable location of pauses in certain short oligonucleotides: AUG, AUU, AAU and some others is in favour of the hypothesis. PMID- 6265763 TI - [Study of Ca-dependent ATPase of sarcoplasmic reticulum by the use of selectively bound spin labels]. AB - The dependence of the ESR spectral parameters of spin labelled sarcoplasmic reticulum membranes on the amount of bound maleimide spin label is found which is shown to result from non-equivalence of the different SH groups rather than from enzyme activity changes on modification. Some structural characteristics (local polarity, the accessibility to water soluble reagents, the distance from ATP binding site) of the fast and slowly reacting SH groups were studied using selective labelling technique. The main contribution to the ESR absorption for both types of thiol groups gives the spin labelled Ca-ATPase. The slow rotational mobility of both types of strongly immobilized spin labels is measured using microwave saturation technique. This mobility is shown to be due essentially to intramolecular motion in different regions of the Ca-ATPase. The frequency of this motion correlates with the enzyme activity and it is sensitive also to the interaction of the enzyme with the substrates (ATP, acetylphosphate) and to the changes of lipid-protein interaction by temperature variation. PMID- 6265764 TI - [Cyclic GMP-induced structural transitions of photoreceptor membranes]. AB - The influence of cyclic GMP on the structural state of photoreceptor membranes was studied. The spin probe technique was used to obtain the dependences of microviscosity of lipid domains of membranes on cGMP concentration. It was shown that microviscosity of 5-doxylsteraric acid environment in rod outer segment, disc and plasma mambranes changed at concentrations of 2.10(7); 5.10(-6) and 6.10(-6). Non-cyclic GMP was ineffective. The ultrasound treatment of membraneous samples resulted on disappearance of the structural changes. PMID- 6265765 TI - Miniaturized afterloading for brachytherapy of cancer. PMID- 6265766 TI - [Forum on hypertension. Part 5. New anti-hypertensive agents in the therapy of hypertension]. PMID- 6265767 TI - [The risk of gastrostomy in childhood. Sources of error and prevention (author's transl)]. AB - The indication for gastrostomy in childhood arises from the possibilities of decompression and enteral feeding. The demand for an operative procedure to children involves simple technique, safety, efficacy and uncomplicated nursing. The most important sources of error in the creation of a gastrostoma arise from the position and size of the catheter, atraumatic suture technique; on the other hand there is the threat of postoperative extension of the gastrostoma, local infection and sepsis. The results of our own procedure are described and the results given of 172 of our own cases. PMID- 6265768 TI - [Leprosy as a medical emergency]. PMID- 6265769 TI - [Forum on hypertension. Part 8. Hypertension management in pregnancy]. PMID- 6265770 TI - Repair of damage by ultraviolet radiation in xeroderma pigmentosum cell strains of complementation groups E and F. AB - The xeroderma pigmentosum fibroblast strains XP2RO, complementation group E, and XP23OS, group F, were compared with normal human primary fibroblasts with regard to repair of damage induced by 254-nm UV. In XP2RO cells, repair DNA synthesis, measured by autoradiography (unscheduled DNA synthesis = UDS), was about 50% of the value found in normal human cells. In these cells also the removal of UV induced sites recognized by a specific UV-endonuclease proceeds at a reduced rate. By having BUdR incorporated into the repaired regions, followed by the induction of breaks in these patches by 313-nm UV, it was shown that the reduced repair synthesis is not caused by a shorter length of the repair regions in XP2RO, but is solely due to a reduction in the number of sites removed by excision repair. In XP23OS a discrepancy was observed between the level of UDS, which was about 10% of the normal value, and other repair-dependent properties such as UV survival, host-cell reactivation and removal of UV-endonuclease susceptible sites, which were less reduced than could be expected from the UDS level. However, when UDS was followed over a longer period than the 2 or 3 h normally used in UDS analysis, it appeared that in XP23OS cells, the rate of UDS remained constant whereas the rate decreased in normal control cells. Consequently, the residual level of UDS varies with the period over which it is studied. PMID- 6265771 TI - Relative mutagenicity of antineoplastic drugs and other alkylating agents in V79 Chinese hamster cells, independence of cytotoxic and mutagenic responses. AB - The mutagenic and cytotoxic effects of 4 antineoplastic drugs, vinblastine, vincristine, adriamycin and nitrogen mustard and of several monofunctional alkylating agents have been assayed in V79 Chinese hamster cells. Vincristine, vinblastine and nitrogen mustard did not significantly increase the frequency of TGRHGPRT- mutants but were were all highly cytotoxic. Adriamycin and the monofunctional alkylating agents were all significantly mutagenic even at the lowest doses tested (approx. 70% survival level). Induced mutant frequency increased linearly with increasing dose whereas dose-response curves for cytotoxicity for these effective mutagens invariably showed a shoulder followed by an exponential decline. At equitoxic doses the relative mutagenic effectiveness was MNU > ENU > EMS > MNNG > MMS greater than or equal to DMS. MNU was approx. 20 times more effective than MMS and DMS. Measurement of the total amount of alkylation and the relative amounts of reaction with individual DNA bases at approx. equitoxic doses of MNU and DMS indicated a significantly higher O6/N7 ratio after MNU (0.15) than after DMS (0.005). However, approx. equal numbers of mutants/10(5) cells/microM O6-Meguanine were induced by these 2 agents. These results support previous conclusions, that mutagenic and cytotoxic responses are independent in V79 cells. PMID- 6265772 TI - [Interactions between 5-fluorocytosine and polyene antibiotics, resp. imidazole derivatives (author's transl)]. PMID- 6265773 TI - Cyclic 3',5'-adenosine monophosphate levels during the developmental cycle of Trypanosoma brucei brucei in the rat. AB - Intracellular content of cyclic 3',5'-adenosine monophosphate was determined in several strains of Trypanosoma brucei brucei during their growth in rats. In non relapsing infections with the cloned monomorphic strain 110M and with the cloned pleomorphic strain YTatl, the amount of cyclic AMP per 10(9) trypanosomes increased from 30 to over 90 pmol as the parasitemia increased from patency to over 10(9) organisms per ml. This increase was not observed during non-relapsing infections with strain 427. During infections with strain YTatl in both immunocompetent and lethally X-irradiated rats, cyclic AMP content of the parasite increased from 20--20 pmol per 10(9) cells early in logarithmic growth to 65--70 pmol per 10(9) cells at peak parasitemia, then decreased as the transition to intermediate and short stumpy forms commenced. At crisis, basal levels were reestablished when log slender forms were the lowest percentage of the total population and intermediate and short stumpy forms predominated, suggesting a correlation between morphologic type and level of cyclic AMP per cell during fluctuations in parasitemia. Increases in intracellular cyclic AMP were measured during in vitro incubation of the parasite in medium containing potential effectors of the trypanosome cyclic AMP system. Sodium fluoride, adenosine and methyl xanthines stimulated increases in cyclic AMP content while isoproterenol, prostaglandin E1, serotonin, histamine and several trypanocidal drugs were ineffective. The results are discussed in terms of the possible regulatory role of cyclic AMP in differentiation of trypanosomes. PMID- 6265774 TI - Biochemical identification of cutaneous leishmanias by analysis of kinetoplast DNA. II. Sequence homologies in Leishmania kDNA. AB - Kinetoplast DNA (kDNA) has been isolated from the human cutaneous Leishmania isolates, L. tropica major, L. aethiopica and an unknown Kenyan isolate, Leishmania SP48. DNA sequence relationships among these isolates have been studied by restriction enzyme digestion and two phase hybridisation to Southern blots of kDNA covalently coupled to diazobenzyloxymethyl (DBM) paper. The results of this analysis confirm that rapid kDNA sequence evolution is occurring in the Old World leishmanias although some sequence conservation in defined regions of the mini-circle sequence is present. These results emphasise the danger of constructing a rigid Leishmania classification on buoyant density data alone. The covalent binding of kDNA electrophoretic separations to DBM paper permits the construction of a DNA sequence "library' which can be used in the classification and diagnosis of unknown Leishmania isolates. PMID- 6265775 TI - Biochemical and ultrastructural alterations produced by miconazole and econazole in Trypanosoma cruzi. AB - Miconazole and econazole, two fungicide imidazole derivatives, completely inhibited growth of Trypanosoma cruzi (Tulahuen strain) at concentrations of about 20 muM. Culturing of T. cruzi in the presence of lower doses of imidazole derivatives produced: decrease of 5,7-diene sterol content in epimastigotes (including ergosterol); disappearance of the nuclear chromatin, vacuolization and decrease in the electron density of the cytoplasm; selective surface alterations as revealed by an increased response to wheat-germ- and phytohemagglutinin. At variance with the effect of miconazole on Candida (De Nollin et al. (1977) Antimicrobial. Agents Chemother. 11, 500-513), miconazole and econazole, under the experimental conditions used, did not increase the rate of hydrogen peroxide generation by T. cruzi. PMID- 6265776 TI - A rapid method for the isolation of intact glycosomes from Trypanosoma brucei by Percoll -gradient centrifugation in a vertical rotor. AB - A rapid method for the isolation of intact glycosomes from trypanosoma brucei is described. A post large-granule extract is subjected to density-gradient centrifugation on isotonic Percoll in a vertical rotor. This results in a good separation of the glycosomes, which equilibrated at 1.09 g/cm3, from other cellular components. Glycosomes isolated from such a gradient are 9-fold purified relative to the starting homogenate with a yield of 25%. Their glycolytic enzymes exhibit a high latency indicative of an intact glycosomal membrane. PMID- 6265777 TI - Physical conditioning facilitates the exercise-induced secretion of beta endorphin and beta-lipotropin in women. PMID- 6265778 TI - What makes us run? PMID- 6265779 TI - Immunosuppressive effect of tetrahydrocannabinol plus cyclophosphamide. PMID- 6265780 TI - Herpesvirus-induced antigens in squamous-cell carcinoma in situ of the vulva. AB - Antigens induced by herpes simplex virus Type 2 (HSV2) were found to be associated with squamous-cell carcinoma in situ of the vulva in nine of 10 patients. The HSV2-induced antigens are DNA-binding proteins that are normally present in the nuclei of infected cells, but in the cells of the carcinomas in situ they were found in the cytoplasm. Whole-virion structural antigens were not present, although there was serologic evidence of previous HSV2 infection in patients tested for the presence of antibodies. The observations reported here and the recent parallel rise in the prevalence of both HSV2 infections and vulvar carcinoma in situ, particularly in women under 40 years of age, suggest an association of HSV2 infection with this type of neoplasia, the nature of which remains to be determined. PMID- 6265781 TI - Lowering plasma cholesterol by raising LDL receptors. PMID- 6265782 TI - Type 2 herpes simplex virus and vulvar carcinoma in situ. PMID- 6265783 TI - Molecular considerations relevant to the mechanism of active transport. AB - A small group of closely related proteins is responsible for all active transport in animal cells, and inorganic cations are the only substances transported by these enzymes. They share a common kinetic mechanism in which two fundamental conformations participate, each receiving and dispatching substrates from its unique side of the membrane. During transport, the cations must pass through their enzyme to cross the membrane and intense interest is currently focused on the possibility that the path which they follow lies within the interface between two discrete subunits in a dimeric structure. Although 'half-of-sites' behaviour, consistent with this hypothesis, has been reported, it is now known that systematic errors were responsible for this mistaken conclusion. The number of protomers which comprise a functional unit of active transport has not been determined. PMID- 6265784 TI - The nus mutations affect transcription termination in Escherichia coli. AB - The nusA1 and nusB5 mutations in a partial suppression of polarity and thus transcription termination in Escherichia coli. As these mutations block the transcription antitermination activity of bacteriophage lambda N gene product, they paradoxically seem to enhance transcription termination at phage termination sites. The rho mutation HDF026 displays almost identical properties. The observations suggest that the nusA and nusB gene products may act as termination factors analogous to rho protein. PMID- 6265785 TI - Termination of transcription by nusA gene protein of Escherichia coli. AB - The nusA gene protein of Escherichia coli and N gene protein of bacteriophage lambda interact in vitro and cooperate in vivo to prevent transcription termination. In vitro the nusA gene protein causes RNA polymerase to pause in the tR2 terminator region of lambda DNA. A completed termination event at tR2 requires both the nusA gene protein and the previously described E. coli termination factor rho. The nusA gene protein is therefore both a transcription termination factor and a protein which couples antitermination factors to the elongating transcription complex. PMID- 6265786 TI - Gene expression in visna virus infection in sheep. AB - Visna is a slow degenerative disease of the central nervous system (CNS) of sheep caused by a nontumorigenic retrovirus. During the course of this disease, visna virus establishes a persistent infection of the CNS, lung and haematopoietic system, despite a specific humoral and cellular immune response. We have studied visna virus life cycle at the single-cell level in choroid plexus of experimentally infected animals, using a very sensitive and quantitative in situ hybridization assay. We report here that although proviral DNA is synthesized in significant amounts, its expression is blocked at the transcriptional level. This restriction of proviral DNA transcription offers an explanation for the slowness of the disease and the persistence of the infection. PMID- 6265787 TI - Fast inward and outward current channels in a non-spiking neurone. AB - Although the crustacean coxal receptors and no-spiking, indirect pharmacological and electrophysiological evidence suggests that fast sodium channels may be present in their membrane. The properties of these channels are not known, but it has been suggested that they might be "incompletely differentiated", perhaps lacking "appropriate gating mechanisms", and/or "too sparsely distributed". The former hypothesis is not supported by the results of voltage-clamping experiments done on dendritic segments isolated from these mechanoreceptors. Instead, the results reported here provide direct evidence for a voltage-dependent fast inward current, sensitive to tetrodotoxin (TTX) and requiring external sodium (but not calcium). This current is shunted by a transient fast outward current, also voltage dependent, and it is suggested that this shunting may account, at least in part, for the non-spiking behaviour of the coxal receptors. PMID- 6265788 TI - Inhibition of smooth muscle tension by cyclic AMP-dependent protein kinase. AB - beta-Adrenergic relaxation of smooth muscle by catecholamines has been associated with elevated levels of cyclic AMP. The question arises whether subsequent activation of cyclic AMP-dependent protein kinase has a role in the regulation of smooth muscle contraction. There is substantial evidence that a Ca2+-activated myosin light chain kinase/phosphatase system regulates smooth muscle contraction, and Adelstein et al. have shown that the catalytic subunit of cyclic AMP dependent protein kinase plays a part in this regulation, by phosphorylation of the high molecular weight subunit of the light chain kinase, which results in a decrease in the activity of the kinase. Here we have shown for the first time that the catalytic subunit of the protein kinase inhibits Ca2+-activated tension in skinned smooth muscle fiber preparations. PMID- 6265789 TI - Human transforming growth factors induce tyrosine phosphorylation of EGF receptors. AB - Cultured cell lines of human tumour origin as well as cells transformed by various RNA tumour viruses secrete low molecular weight polypeptide transforming growth factors (TGFs). In addition to competing with epidermal growth factor (EGF) for binding to its cellular receptor, TGFs can transform morphologically fibroblast and epithelial cells in culture. In view of accumulating evidence that tyrosine phosphorylation activity is associated with the transforming genes of various tumour viruses, we determined whether phosphotyrosine levels were elevated in these human tumour cells. We show here that TGFs produced by human tumour cells induce phosphorylation of specific tyrosine acceptor sites in the 160,000-molecular weight (160 K) EGF receptor. PMID- 6265790 TI - Gene conversion between duplicated genetic elements in yeast. AB - The mitotic recombination behaviour of a duplication of the his4 region on chromosome III in the yeast Saccharomyces cerevisiae was studied. The major recombination event between the duplicated segments is gene conversion unassociated with reciprocal recombination. The rad52-1 mutation preferentially decreases mitotic gene conversion. These results suggest that mitotic gene conversion may occur by a different pathway from that occurring in meiosis. This mitotic gene conversion may be important in yeast mating type interconversion and the maintenance of sequence homogeneity in families of repeated eukaryotic genes. PMID- 6265791 TI - The phosphatidylinositol cycle and the regulation of arachidonic acid production. PMID- 6265792 TI - 4',6-Dichloroflavan (BW683C), a new anti-rhinovirus compound. PMID- 6265793 TI - Sequence dependence of the helical repeat of DNA in solution. PMID- 6265794 TI - Sequence-dependent helical periodicity of DNA. PMID- 6265795 TI - In vivo consequences of plasmid topology. PMID- 6265796 TI - Sequence homologies between tonin, nerve growth factor gamma-subunit, epidermal growth factor-binding protein and serine proteases. PMID- 6265797 TI - Expression of herpesvirus-induced antigens in human cervical cancer. PMID- 6265798 TI - Regenerative and passive membrane properties of isolated horizontal cells from a teleost retina. PMID- 6265799 TI - Adrenaline activation of phosphofructokinase in rat heart mediated by alpha receptor mechanism independent of cyclic AMP. PMID- 6265800 TI - Effect of ions on the light-sensitive current in retinal rods. AB - The effect of ions on the light-sensitive current of retinal rods was studied by sucking the inner segment into a tightly fitting capillary with the outer segment projecting into a flowing solution. This new method showed that the light sensitive pathway, in which Na+ is the normal carrier of current, has an ionic selectivity different from that of other known sodium channels. External calcium has a striking effect on the current, which increased about 20-fold when all calcium was removed. Reducing the sodium concentration gradient greatly prolonged the response to a flash of light, as would be expected if internal calcium blocks sodium channels and if light releases calcium which is subsequently extruded by a sodium-calcium exchange mechanism. PMID- 6265801 TI - The p21 src genes of Harvey and Kirsten sarcoma viruses originate from divergent members of a family of normal vertebrate genes. AB - The Harvey and Kirsten strains of murine sarcoma virus encode enzymatically and serologically related p21 src proteins which are required for virally mediated cellular transformation. The genes in each virus encoding p21 show such extensive divergence from each other that cloned probes from these genes detect distinct sets of cellular genes in the DNA from several vertebrate species. These data suggest that cellular p21 sarc genes constitute a divergent family of vertebrate genes that can regulate the growth of cells. PMID- 6265802 TI - Extrachromosomal circular copies of the eukaryotic transposable element copia in cultured Drosophila cells. PMID- 6265803 TI - Transformation of rat cells by an altered polyoma virus genome expressing only the middle-T protein. AB - A modified polyoma virus genome has been constructed which can encode the middle T protein, but not the large-T or small-T proteins. This was achieved, starting with the full length viral DNA inserted into a plasmid vector, by replacing a small genomic restriction fragment spanning the middle-T intervening sequence with the equivalent fragment from a cloned partial cDNA copy of the middle-T protein mRNA. Transfection of the modified viral DNA into cultured rat cells efficiently induced the formation of transformed cell foci which gave rise to cell lines that grew as tumours after injection into Fisher rats. The only viral early-region antigen synthesized by the cell lines was the middle-T protein. Expression of the middle-t protein is therefore sufficient to establish and maintain a transformed state. The viral mRNA produced by two of the transformed cell lines was structurally indistinguishable from the normal middle-T mRNA found in productively infected cells, suggesting that RNA splicing is not an essential step in the biogenesis of this messenger. PMID- 6265805 TI - Tonic in vivo inhibition of rabbit myometrial adrenergic receptors. PMID- 6265804 TI - Immunocytochemical localization of glutamic acid decarboxylase in monkey striate cortex. AB - Neuronal cell bodies and synaptic terminals positive for glutamic acid decarboxylase, the enzyme responsible for synthesizing gamma-amino butyric acid, have been located by immunocytochemical staining in all layers of the macaque monkey cortex. In layers II and III the staining pattern of periodic dots is identical with that seen in sections stained for cytochrome oxidase. The rows of dots run parallel with the ocular dominance columns, suggesting that the labelled neurones are preferentially related to each eye. PMID- 6265806 TI - Multiple copies of iso-insertion sequences of IS1 in Shigella dysenteriae chromosome. PMID- 6265807 TI - Oncogenicity of three strains of avian leukosis virus in White Leghorn chicks of BK line. PMID- 6265808 TI - Two different biophases for adrenaline released by electrical stimulation or tyramine from the sympathetic nerve endings of the dog saphenous vein. AB - To study the distribution of alpha- and beta-adrenoceptors dog saphenous vein strips were electrically stimulated (2ms, 30 V, 0.25--20 Hz). The strips either had spontaneous tone (contraction experiments) or were contracted by 0.28 microM prostaglandin F2 alpha in the presence of 7 microM phentolamine (relaxation experiments). In strips without preloading or in strips preloaded with (--) noradrenaline alpha-adrenoceptor-mediated excitatory responses were readily evoked (contraction experiments) but not beta-adrenoceptor-mediated inhibitory responses (relaxation experiments). In strips preloaded with (--)-adrenaline both alpha-(contraction experiments) and beta-effects (relaxation experiments were readily elicited by electrical stimulation and by tyramine. Thus, strips preloaded with (--)-adrenaline were used to compare alpha- with beta-effects. In these strips the latency between the beginning of the electrical stimulation and the onset of the response was longer for beta- than for alpha-responses. The same applies to responses to exogenous (--)-adrenaline. However, the ratio "latency for beta-/latency for alpha-responses" was 3.6 +/- 0.2 (n = 8) for responses to electrical stimulation and 1.8 +/- 0.1 (n = 12) for responses to (--)-adrenaline (P less than 0.001). Cocaine (12 microM) enhanced the alpha-effect elicited by electrical stimulation 2.8 +/- 0.2 (n = 7) times but did not change the beta effect, whereas U-0521 (50 microM) enhanced the beta-effect 3.4 +/- 0.2 (n = 8) times without changing the alpha-effect. In strips preloaded with (--)-adrenaline also tyramine caused concentration-dependent beta-responses (relaxation experiments). The concentration of phentolamine and prazosin required to inhibit contractions caused by electrical stimulation were about 5--7 times higher than those required to inhibit contractions caused by exogenous adrenaline or noradrenaline, whereas propranolol was equipotent in reducing beta-responses to adrenaline released by electrical stimulation and to exogenous adrenaline. Our results strongly support the view that alpha-adrenoceptors are in close contract with the nerve endings and beta-adrenoceptors are in close proximity of COMT in a vessel with the nerve endings evenly distributed throughout the media. PMID- 6265810 TI - Effects of some GABA-mimetic drugs on the antinociceptive activity of morphine and beta-endorphin in rats. AB - Intracerebroventricular administration of muscimol, a potent GABA-receptor agonist, counteracted the antinociceptive effect of morphine or beta-endorphin in rats as measured by the "tail flick" method. Muscimol's activity was reversed by bicuculline. Isoguvacine, another GABA agonist, as well as nipecotic acid and guvacine, two inhibitors of neuronal and glial uptake of GABA, also antagonized morphine's antinociceptive effect. A role of the central GABA-ergic system in mediating opiate antinociception is proposed. PMID- 6265809 TI - The noradrenaline receptor coupled adenylate cyclase system in brain. Lack of modification by changes in the availability of serotonin. AB - The present studies were undertaken to ascertain whether or not an alteration in the availability of serotonin (5HT) can modify central noradrenergic function at the level of the noradrenaline (NA) receptor coupled adenylate cyclase system in brain. The chronic but not acute administration of the 5HT uptake inhibitors amitriptyline and chlorimipramine reduced the sensitivity of the cyclic AMP generating system to NA in the limbic forebrain. This subsensitivity was linked to a decrease in the Bmax value of beta-adrenergic binding sites without appreciable changes in the Kd values, as assessed by specific 3H dihydroalprenolol binding. The specific 5HT uptake inhibitor fluoxetine did not change either the responsiveness of the cyclic AMP generating system to NA or the density of beta-adrenergic receptor sites. Raphe lesions which selectively reduced the level of 5HT also did not cause any changes in the neurohormonal responsiveness or the density of beta-adrenergic receptor sites. In contrast, medial forebrain bundle lesions which reduced the levels of both 5HT and catecholamines (NA and dopamine) in the forebrain, increased the responsiveness of the cyclic AMP generating system to NA. It can thus be concluded that a selective change in the availability of 5HT per se does not modify noradrenergic receptor function at the level of the NA receptor coupled adenylate cyclase system. The subsensitivity of the noradrenergic receptor system developed following amitriptyline and chlorimipramine may in all likelihood be due to the in vivo conversion to the secondary amines, nortriptyline and desmethylchlorimipramine respectively. These secondary amine metabolites are potent inhibitors of the NA reuptake and consequently could be responsible for the demonstrated in vivo down-regulation of central adrenergic receptor function (homospecific down-regulation). PMID- 6265811 TI - The protective properties of dietary fiber. PMID- 6265812 TI - [Bilateral primary germ cell tumors of the testis]. PMID- 6265814 TI - Glycoprotein and protein composition of bovine leukemia virus (BLV). AB - Highly purified preparation of bovine leukemia virus (BLV) was obtained by the method described in this communication. BLV was isolated from cell-free culture medium, harvested from BLV-producing cell-line FLK. Polyacrylamide gel electrophoresis of BLV proteins and glycoproteins, in comparison with avian myeloblastosis virus (AMV), confirmed high purity of BLV preparations. Molecular weights of some BLV-proteins and glycoproteins were calculated. By employing polyacrylamide gradient 5 to 30% it was found that BLV structural protein p15 contains at least two components. PMID- 6265813 TI - Isolates of avian sarcoma virus Bratislava 77 (B77) oncogenic for mammals do not contain an excess of transformation-defective mutants. AB - Several isolates of the avian sarcoma virus Bratislava 77 (B77), used in tumor induction in rats, hamsters and mice, were tested for the excess of spontaneously segregated transformation-defective mutants (tdB77). The question was asked whether these td mutants could interfere with transforming sarcoma viruses at tumor induction in mammals. It was found that the B77 virus isolates used in successful sarcoma induction in mammals did not contain an excess of td mutants. One virus isolate which had an excess of td mutants did not induce tumors in mammals. The further characterization of the rescued viruses from virogenic mammalian cells showed that all rescued viruses had the same sub-group C specificity as the original isolate of B77 virus. The integration of the viral genome into mammalian cellular genome did not alter transforming ability of the rescued viruses on duck embryo cells. It seems that propagation of B77 virus in conditions in vivo did not support the segregation, and accumulation of an large excess of td mutants in stocks of B77 virus. PMID- 6265815 TI - Proliferation rate--drug sensitivity relation in clones isolated from heterogeneic tumor cell population. AB - Four separate cell clones were isolated from parental rat RBB/R cell line. Sensitivity of clones to 3-oxauracil varied, and was dependent on the proliferation rate of particular clone. Colony formation method was more appropriate than 3H-thymidine incorporation for determination of post-treatment surviving cells. PMID- 6265816 TI - Varicella-zoster antibodies in patients with Hodgkin's disease. AB - Statistically significant differences in mean varicella-zoster antibody titre was found between the normal population and Hodgkin's disease group. No difference in mean antibody titre between the four histological categories of the disease was found. PMID- 6265817 TI - Host range of murine sarcoma virus, its host modification and phenotypic mixing with endogenous virus. AB - The M(MSV)AG-50 cells produce competent ecotropic sarcoma virus which is able to transform several rodent embryo cells and replicate in them. The expanded host range has shown that the virus acquired some host information which facilitate the transformation of heterologous cells. The transformed cells were XC positive and with transformed phenotype in vitro. The genome of mouse sarcoma virus from nonproducer rat liver cells could be rescued by xenotropic endogenous virus. The obtained virus has shown the augmented host range for various embryo cells and for some mammalian cell lines as well. The virus with xenotropic coat efficiently transforms the cells, yielding cells with transformed phenotype. The majority of this virus were phenotypically mixed virions, with minority of probably recombinant virus as suggested by XC test. The modification of the virus during the passage through heterologous cells is discussed. PMID- 6265818 TI - [Intra operative embolization of unresectable cerebral arterio-venous malformations. Occlusion attempt by means of a delayed polymerization mixture. Report of two cases (author's transl)]. AB - Two cases of unresectable intra-cranial arterio-venous malformation (AVM) are reported, treated by direct intra-operative embolization. A 50% mixture of Butyl 2-Cyano-Acrylate and Mono-Iodo-Stearate of Ethyle (Duroliopaque) was used after catheterization of some of the feeding cortical arteries. No intra-operative angiography was performed. The first patient, admitted after subarachnoid hemorrhage and presenting with a mild transient right hemiparesia and aphasia, showed evidence of a left temporal AVM with a left middle cerebral artery supply and contribution from the left cerebral posterior artery. The AVM was embolized with 3 cc of the mixture. A mild aphasia occurred after surgery and completely recovered after two weeks. Roughly half of the AVM was occluded on the postoperative angiograms. The second patient suffering from a long history of seizures had a huge right frontal AVM, with a right middle cerebral artery and right anterior cerebral artery supply, and contribution from a right lenticulostriate artery, the left anterior cerebral artery and the right posterior cerebral artery. The AVM was embolized with 7 cc of the mixture. A complete palsy of the left upper limb occurred after surgery, with complete recovery after two weeks. On the post-operative angiograms, more than three fourth of the AVM was occluded. PMID- 6265819 TI - Immunocytochemical localization of beta-endorphin-containing neurons in the rat brain. AB - beta-Endorphin-containing neurons in the rat central nervous system were localized using three improvements of the unlabelled antibody-enzyme bridge immmunocytochemical technique. These improvements were (1) the use of brains from colchicine-treated rats; (2) the proteolytic pretreatment of sections with pronase, and (3) a 'double-bridge' staining procedure. In addition to the known localization of beta-endorphin-like immunoreactivity in perikarya in the medial basal hypothalamus, we have observed nerve fibers and terminals with beta endorphin-like immunoreactivity to be more widely distributed than reported in previous studies. This includes discrete areas of the septal, preoptic, hypothalamic, thalamic and subthalamic regions, the amygdala, the periaqueductal gray, the inferior colliculus, the nucleus tegmenti pontis, the nucleus raphe dorsalis, several regions of the reticular formation, the locus ceruleus, the parabrachial nuclei, the mesencephalic trigeminal nucleus, the nucleus raphe magnus, the solitary tract and the nucleus of the solitary tract. The distribution of beta-endorphin-like immunoreactivity is in good agreement with many of the physiological, neuroendocrine and behavioral effects attributed to this peptide such as analgesia, the regulation of the release of pituitary hormones, thermoregulation and feeding behavior. This implicates beta-endorphin as an important neurotransmitter or modulator with specific functions within the central nervous system. PMID- 6265820 TI - Serum fatty acid patterns in hereditary motor and sensory neuropathies. AB - The fatty acid pattern of serum lecithin was studied in 31 children with hereditary motor and sensory neuropathies (HMSN) of types specified in the classification of Dyck et al. (1975). In 30 children no relevant changes were revealed. The remaining patient had changes which were reversible and were considered to be independent of the polyneuropathy. It is concluded that primary defects of fatty acid metabolism do not characterize the well-defined types I, II and III of HMSN. PMID- 6265821 TI - Polyneuropathies - neurophysiological diagnostic points. AB - A survey of clinical neurophysiological methods of importance in the diagnosis of polyneuropathies is given. Electromyography (EMG) is essential and should be performed in all four extremities. If the EMG findings with concentric needle electrodes are equivocal, fibre density determination with single fibre electrodes can give useful information. The various methods of determining conduction velocities in motor and sensory nerve fibres are described. Recent advances in the examination of function in sensory fibres are presented, particularly microneurography and psychophysical methods. The applicability of the methods with regard to the age of the patient is discussed. PMID- 6265822 TI - Pooled European series of hereditary peripheral neuropathies in infancy and childhood. A "correspondence work shop" report of the European Federation of Child Neurology Societies (EFCNS). AB - A European series of 287 cases of "pure" peripheral neuropathy, pooled from 14 neuropediatric centres, has been analysed retrospectively with particular emphasis on the hereditary motor and sensory neuropathies (HMSN) which comprised 241 of the patients. Due to incomplete information in many records it has only been possible to make a crude analysis of the problems of diagnosis and classification. More than half of the HMSN series conform to the diagnosis of HMSN I (charcot-Marie-Tooth-Roussy-Levy disease), A relatively homogeneous group but with large variations in age of onset and severity of disease between individuals in the same family. In five of the 147 cases the onset was at or before birth. An overdiagnosis of HMSN III (Dejerine-Sottas' disease) was considered probable due partly to an unawareness of the high frequency of subclinical carriers among parents in families with HMSN I. Cases with axonal types of polyneuropathy, appearing sporadically or with suspected autosomal dominant (HMSN II) or recessive inheritance, occurred with unexpected frequency in children. This group of 60 pooled European cases was considered worthy of a particularly thorough follow-up and further investigation in order to achieve a better delineation between different subtypes. Cases with an onset before birth or very early in infancy (20 cases) comprised a heterogeneous group with some special subtypes. Surprisingly enough, no less than 5 of the 20 cases represented HMSN I. Cerebrospinal fluid protein levels were not found to be useful for differentiating various types of HMSN. Elevated levels were revealed in about half of the examined cases of HMSN I and in 75% of cases of HMSN III, the levels of increase showing a marked overlap. In nearly all of the axonal cases investigated the CSF protein was normal. PMID- 6265823 TI - Alteration in beta-adrenergic receptor binding in brain, lung and heart during morphine and alcohol dependence and withdrawal. PMID- 6265824 TI - Mechanisms of selective signalling by calcium. Based on an NRP Work Session. PMID- 6265825 TI - Enzymatic activity of pial arterial blood vessels of the rabbit in normal and ischemic conditions. PMID- 6265826 TI - [Carcinomas in situ of the breast]. AB - In situ carcinomas of the breast represent a clinical reality of recent decades that oncologists have to face today. Their observation is rendered increasingly frequent thanks to the improvements made in radiological techniques for early diagnosis and mass screening, and better health education. Reference is made to cases of lobular and ductal in situ cancer observed at the Bologna Surgical Clinic. Recommendations are made with respect to the drawing up of a rational treatment plan. PMID- 6265827 TI - [Bronchial cylindroma (adenocystic carcinoma)]. PMID- 6265828 TI - [Mixed tumor of an ectopic salivary gland. Presentation of a case]. AB - A case of mixed tumour in an island of ectopic salivary glandular tissue at the right nostril and surrounding labial skin is reported. An anatomopathological classification of salivary neoplasias is provided and the histological picture of mixed tumours described. Stress is laid on the rarity of the finding. An extensive tissue area was removed because the neoplasia was a recurrence of a previous intervention (done by others) not followed up by histological examination. PMID- 6265829 TI - [Changes in the lipid pattern of atherosclerotic arteriopathic patients treated with a diet enriched with raw cereal fiber. Analysis of the results]. PMID- 6265830 TI - [Endocrine pancreatic tumors]. PMID- 6265831 TI - [Broncho-alveolar cancer. Contribution toward a further clinical classification]. AB - The incidence of alveolar bronchiole carcinoma in 1665 histologically verified cases of lung cancer is referred to on the basis of autoptic observations made at the San Luigi Gonzaga Hospital of Orbassano between 1973 and 1979. In agreement with the most recent reviews of the question, a net increase in the absolute values of this form of cancer was confirmed. Reviewing the personal series, stress is laid on the problems of clinico-nosological classification of a.b.c. which, although defined by its peculiar histological expression, presents diagnostic and interpretative problems that are not easy to solve. PMID- 6265832 TI - [Vasoactive intestinal polypeptide in digestive processes in the Verner Morrison syndrome]. AB - Some physiological digestive processes thought to be under the control of VIP ergic neurones are presented. The etiological role of the Vasoactive Intestinal Polypeptide in the Verner Morrison syndrome is discussed. PMID- 6265834 TI - [The role of benign tumors and mammary dysplasias in cancerogenesis as related to lysosomal alpha-arylsulfatase and beta-glucoronidase enzyme activity]. PMID- 6265833 TI - [Hormonal control of puberty]. PMID- 6265835 TI - [Electrophysiological studies in encephalopathy and peripheral neuropathy in chronic uremia]. PMID- 6265836 TI - Abandoned synaptic sites in muscles of normal adult frog. AB - In previous investigations light microscopic cholinesterase (ChE) deposits without any nerve were found adjacent to normally occupied parts of a frog neuromuscular synapse [4, 9]. After identifying one such site at the light microscopic level ultrathin sections were cut and viewed with an electron microscope. ChE reaction product-filled secondary, clefts were observed in the region studied but a nerve was invariably missing. From this it is concluded that these loci are former synaptic sites from which nerve and Schwann cell have retracted, When incubating muscles with fluorescence-labelled alpha-bungarotoxin, all 23 abandoned sites found in 6 muscles remained bare of visible amounts of label. This indicate that receptor molecules eventually disappear from the synaptic membrane after retraction of the nerve and Schwann cell. No information as to the underlying time schedule of nerve retraction, turnover of ChE and alpha bungarotoxin binding sites was obtained. Taken together with the evidence for synapse new formation in untreated frog muscles obtained previously [9, 11] the present observations indicate some ongoing remodeling of frog neuromuscular junction. PMID- 6265837 TI - Immunocytochemical localization of tetanus toxin to synapses of spinal cord. AB - In this study, tetanus toxin was microinjected into the ventral horn of the spinal cord of rats, producing local tetanus. The toxin was localized by immunocytochemical methods. Reaction product was visualized within synaptic terminals, particularly those on the soma and dendrites of motor neurons. The distribution of staining terminals was similar to that of labeled synapses, visualized by autoradiography, after microinjection of either [125I]tetanus toxin or [3H]glycine, the latter a major inhibitor transmitter in the spinal cord. PMID- 6265838 TI - Pentobarbital enhances [3H]diazepam binding to soluble receptors at the benzodiazepine--GABA-receptor-ionophore complex. AB - Pentobarbital enhances [3H]diazepam binding to soluble receptors in a dose dependent and saturable manner. Half-maximal enhancement occurred at 110 micrometers pentobarbital. This enhancement was due to an increase in the affinity of diazepam to its receptor sites. Pentobarbital enhancement was blocked by picrotoxinin and bicuculline. These results are similar to those reported for membranes and suggest that various components of the benzodiazepine--GABA receptor-ionophore complex are intimately associated. PMID- 6265839 TI - Effects of bromocriptine on receptor binding of methionine-enkephalin. AB - Bromocriptine inhibited the binding of methionine-enkephalin (ENK) to rat striatal synaptic membranes in a dose-dependent fashion. The bromocriptine IC50 was 16 micrometers. hill coefficients of bromocriptine were 0.7 and 0.3, suggesting that an allosteric effect was involved in bromocriptine inhibition of ENK binding to its receptor. These data suggest that at least a part of the therapeutic antiparkinsonian effect f bromocriptine is its allosteric effects on the ENK receptor, which influences the function of striatal dopamine neurons and/or of striatal cholinergic neurons. PMID- 6265840 TI - Access to the cerebral cortex of extra-lingual taste inputs in the rat. AB - Rats with their intra-lingual taste nerves (the chorda tympani and the glossopharyngeal nerve) sectioned were trained to avoid drinking 0.5 M NaCl solution by associating NaCl drinking with subsequent LiCl poisoning. The acquired learned aversion in these rats was abolished after ablations of the neocortical area for the intra-lingual taste nerves. This result indicates that extra-lingual taste inputs from the palatine and epiglottal taste buds share the neocortical taste area with intra-lingual taste inputs. PMID- 6265841 TI - Anticonvulsant effects of caerulein, cholecystokinin octapeptide (CCK-8) and diazepam against seizures produced in mice by harman, thiosemicarbazide and isoniazid. AB - Caerulein, cholecystokinin octapeptide (CCK-8) and diazepam delayed the onset of seizures produced by harman and thiosemicarbazide (TSC). Caerulein had the potency of diazepam, whereas CCK-8 was less active by a factor of four. The convulsions induced by isoniazid (INH) were very resistant to both caerulein and diazepam; CCK-8 was not tested against isoniazid. Haloperidol did not influence the effect of TSC; it enhanced isoniazid-induced seizures, and antagonized the convulsant effect of harman. PMID- 6265842 TI - Oat cell carcinoma (apudoma) of esophagus. An ultrastructural study. PMID- 6265843 TI - Guar gum is not a panacea in diabetes management. AB - Guar gum was incorporated into the diets of six insulin dependent diabetics drawn from one general practice. Amounts between 6 and 59.6 g daily were used for four to six weeks and compared with a previous two week control period. Unlike some other studies, little improvement was obtained in diabetic control and a small reduction in cholesterol levels occurred. The guar was well tolerated in amounts below 30 g a day. PMID- 6265844 TI - Herpes simplex encephalitis and vidarabine treatment. PMID- 6265845 TI - Histological evidence for the presence of condylomatous epithelial lesions in association with laryngeal squamous cell carcinoma. AB - The laryngeal specimens obtained from 116 patients with established invasive squamous cell carcinoma of the larynx were histologically assessed with special reference to the detection of morphological manifestations of human papilloma virus (HPV), as newly described in the uterine cervix, i.e. the three different types of condylomas (the papillomatous, the flat and the inverted ones). Epithelial changes fulfilling the criteria of the papillomatous condyloma were found in 15 cases, those of the inverted condyloma in 9 cases, and lesions identical to the flat type condyloma were present in 25 specimens. The role of HPV in the development of these lesions is discussed, and the possibility is raised that HPV might be the agent responsible for or contributing to the development of squamous cell carcinoma of the larynx in man. PMID- 6265846 TI - Primary Small Cell ("Oat Cell") carcinoma of the larynx and hypopharynx. AB - The present paper is a clinico-pathological study of 8 cases of small cell("oat cell") carcinoma of the larynx and hypopharynx investigates at the Section of Pathology of the ENT Department of Padua University during the last 14 years (from January 1966 to December 1969). Besides a review of the world literature, several problems connected with terminology, histogenesis and pathologic patterns (microscopic, histochemical and ultrastructural) and examined, together with the differential diagnosis, clinical aspects and therapeutic approach. The association of small cell carcinoma with squamous cell carcinoma both in the larynx and hypopharynx is reported. PMID- 6265847 TI - [Clinical, laboratory and serological observations in infectious mononucleosis]. PMID- 6265848 TI - [Epstein-Barr virus infections in childhood]. PMID- 6265849 TI - [A new method for the quantitative determination of anti-phospholipase C]. PMID- 6265850 TI - [Iron and infection]. PMID- 6265851 TI - [The incidence of juvenile Epstein-Barr virus infections]. PMID- 6265852 TI - [Recent findings on the viral etiology of acute gastroenteritis--a review]. PMID- 6265853 TI - The pathological assessment of ovarian neoplasms. IV: The sex cord-stromal tumours. AB - All neoplasms of the ovary encountered in a 25-yr study period at the King George V Memorial Hospital were classified according to the World Health Organisation (WHO) Histological Classification of Ovarian Tumours. Of just less than 1700 tumours, 168 fell into the category designated as sex cord-stromal tumours, this report analysing their major clinical and pathological correlates. A detailed histological assessment is then presented, including 4 cases of the recently separated subcategory of sclerosing stromal tumour of the ovary. PMID- 6265854 TI - Reactivity of antisera to antigens of C-type viruses with leucocytes from patients with acute leukaemia. AB - A number of previous studies have suggested that certain C-type viruses from non human primates are associated with acute leukaemia in humans. The present study sought to examine this association further by detection of antigens related to these viruses on the surface of acute leukaemia cells. Antisera against the whole viruses or the major internal protein of simian sarcoma, endogenous baboon and Rauscher viruses were tested against mononuclear cells from patients with acute leukaemia at various stages of their disease in 51Cr release leucocyte dependent cytotoxic assays. A high proportion of the patients had antigens related to these viruses detectable on their blood leucocytes at some stage in their disease whereas with one exception blood leucocytes from non-leukaemic subjects did not. The expression of these antigens did not show a close relation to the number of blast cells in blood detected on morphological grounds. Antigens related to the non-human primate viruses were detected on mononuclear cells from bone marrow samples of several non-leukaemic patients which indicated they were not specifically associated with leukaemia. Antigens related to the Rauscher virus were detected on cells of practically all bone marrow samples tested. These results suggest that assays to detect these antigens would be of limited usefulness to monitor disease activity in patients with acute leukaemia. Their expression on blood leucocytes however appeared strongly associated with acute leukaemia and further studies to assess the prognostic and epidemiological significance of detection of these antigens appears warranted. PMID- 6265855 TI - Fetal preventive medicine: teratogens and the unborn baby. PMID- 6265856 TI - Fibrous lesion of the bowel complicating the management of bilateral Wilms' tumor. AB - A 31 month old black male with known bilateral Wilms' tumor, who had right nephrectomy and left lower pole heminephrectomy developed a palpable mass in the left lower quadrant. Several studies could not clearly determine the nature of the mass lesion, a laparotomy was performed, a keloid-like lesion was found in the bowel wall. PMID- 6265857 TI - Hormonal control of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities in the fetal rat kidney. AB - Triamcinolone (20 microgram per fetus) administered in utero to term rat fetuses (day 21 of gestation) increases the activities of renal G-6-Pase and PEPCK. The absence (or marked decrease) of circulating corticosteroids in fetuses from adrenalectomized, metopirone-treated mothers has, however, no clear effect on the enzyme activities. Therefore, it is doubtful that corticosteroids play a role in the development of G-6-Pase and PEPCK activities during the fetal period of life. In 21-day-old fetuses entirely decapitated on day 18, both enzyme activities are lower than intact fetuses of the same litter (G-6-Pase, -48%; PEPCK, -36%). In partially decapitated fetuses, the activity of G-6-Pase remains at the control level, whereas the PEPCK activity is clearly reduced (-39%). These results strongly suggest that on the last day of gestation the hormone group of parathormone, calcitonin, or thyroxine controls the G-6-Pase activity, whereas the hypothalamo-hypophysis system is implied in the development of PEPCK activity. Parathormone (1 unit per fetus) administered to decapitated fetuses completely restores the G-6-Pase activity. Neither rat growth hormone, synacthene, nor arginine vasopressin has significant effects on the activity of PEPCK in the kidneys of decapitated fetuses. The administration of 0.5 mumole of dibutyryl-cAMP or cyclic adenosine 3':5'-monophosphate (cAMP) to decapitated fetuses completely restores the activity of renal PEPCK, suggesting that the development PEPCK is controlled by cAMP-dependent hormone. The same dose of dibutyryl-cAMP has no effect on the activity of G-6-Pase; cAMP produces a slight but significant increase of this enzyme activity. PMID- 6265858 TI - The effect of bilirubin on the function of hamster small intestine. AB - Jaundice phototherapy is associated with a significant incidence of watery diarrhea. We have postulated that acute intestinal secretion, rather than malabsorption of dietary carbohydrate, is an effect of a photoproduct of bilirubin upon the intestinal mucosa. Because of major effect of phototherapy is the hepatic excretion of nonconjugated bilirubin, we investigated the effect of bilirubin on small intestinal function in the hamster in vivo. The entire small intestine was luminally perfused in vivo with solutions containing bilirubin (0.125 to 0.75 mmole/liter) and net water and sodium fluxes were measured. Control animals absorbed both water (J H2O(net) = 58.9 microliter/min/g) and sodium (J Na(net) = 4.55 microEq/min/g), but animals perfused with bilirubin (greater than or equal to 0.25 mmole/liter) exhibited secretion of water (J H2O(net) = -39.0--85.9) and sodium (J Na(net)=-9.91--18.24). The rate of water secretion was positively related to the concentration of bilirubin in the infusate (r=0.749; p less than 0.001). The concentration of bilirubin in ultrafiltrates of perfusate was likewise positively related to its concentration in the infusate (r = 0.844; p less than 0.001), indicating the potential importance of soluble forms of bilirubin in inducing secretion. Possible epithelial injury was studied by measuring the concentration of DNA in the perfusate and the activity of disaccharidases in postperfusion mucosa, and the possible role of cyclic adenosine monophosphate as a mediator of the secretory process was investigated by determining its concentration in postperfusion mucosa. Perfusion with 0.5 mM bilirubin, which produced significant secretion, did not cause loss of DNA (0.284 versus 0.244 mg/liter) or mucosal lactase activity (56 versus 53 units/g) or enhancement of cyclic adenosine monophosphate concentration (14.9 versus 14.12 pmoles/mg protein). PMID- 6265860 TI - American Academy of Pediatrics: Committee on Nutrition. Plant fiber intake in the pediatric diet. PMID- 6265859 TI - Cystic fibrosis "factor(s)": present also in sera of Schwachman's pancreatic insufficiency. AB - Using an in vivo closed-loop technique in rat jejunum, we have confirmed previous in vitro studies that cystic fibrosis (CF) serum inhibits water, sodium, and glucose absorption and transmural potential difference. CF heterozygote serum or sera form children with diarrhoeal disorders not associated with exocrine pancreatic insufficiency had no effect of transport. Sera from patients with Shwachman's syndrome and exocrine pancreatic insufficiency had identical effects to CF serum. These results challenge the specificity of the CF "factor." PMID- 6265861 TI - Block of Na channels in the membrane of myelinated nerve by benzocaine. AB - The actions of the neutral local anesthetic benzocaine on Na channels were studied in voltage-clamp experiments on single myelinated nerve fibres of the frog by measurements of sodium currents, asymmetry currents, and sodium current fluctuations. 2. 1 mM benzocaine reduced the peak Na currents during various depolarizations V between 20 and 120 nV to 63% of their control values but did not change the time constant of Na activation. 3. 1 mM benzocaine altered asymmetry currents during 1 ms pulses V between 20 and 120 mV in the same was as the early Na currents: It reduced the amplitude to 64% but did not affect the kinetics of the currents. 4. The charge displacement of the asymmetry current during the pulse (Qon) was compared with the charge displacement after the pulse (Qoff). Without benzocaine the relative charge Qoff/Qon Declined to a constant level (0.42 at V = 40mV, 0.25 at V = 100 mV) with increasing pulse durations. In the presence of 1 mM benzocaine the charges Qoff after pulses to V = 40 or 100 mV are almost independent of pulse duration and approximately equal to the control Qoff values after 5.6 ms pulses. Thus, the immobilizations caused by Na inactivation and benzocaine are not additive. 5. Na currents and Na-current fluctuations were recorded during depolarizations V between 24 and 48 mV in the presence of 0.1 mM benzocaine and 7 microM Anemonia toxin II. A lower limit of 8.6 pS was derived for the conductance of a single Na channel. The value agrees with other estimates of the conductance of Na channels which had not been treated by local anesthetics. This suggests an "all-or-none blocking" of Na channels by benzocaine. PMID- 6265862 TI - [Scintigraphy with technetium dimercaptosuccinic acid (99 m TC DMSA). Contribution to the functional assessment of individual kidneys (author's transl)]. AB - Renal uptake of 99m Tc DMSA was used to evaluate the renal function of 16 healthy subjects (controls) and 115 patients with various urinary tract diseases. Scintigraphic examination was carried out 6 hours after an intravenous injection of the product. In the 16 controls Tc DMSA uptake was 25.7 +/- 2.48% in the right kidney and 24.4 +/- 2.86% in the left kidney. In 36 patients with one single hypertrophied kidney, there was a correlation (r = 0.850) between creatinine clearance and Tc DMSA uptake, which was higher than in normal subjects (39.23 +/- 9.9%). In the group of 68 patients with unilateral (31) or bilateral (37) renal disease, a significant correlation (r = 0,725) was observed between kidney-to kidney ratios of urea clearance and Tc DMSA uptake, so that renal impairment could be quantified. Quantitative scintigraphy did not appear to be of assistance in the remaining 11 patients with obstructive uropathy, as it overestimated renal function. The results obtained with 99 m Tc DMSA scintigraphy should be helpful in choosing between nephrectomy and conservative surgery and in assessing the degree of compensatory hypertrophy in single kidneys. PMID- 6265863 TI - [Neuropathy associated with ichthyosis and splenomegaly in an adult patient. Possible relationship with altered glycosphingolipid metabolism (author's transl)]. AB - The authors report on the case of a 40-year-old woman presenting with ichtyosiform erythroderma, central and peripheral neuropathy, splenomegaly and low serum haptoglobin levels. The patient's blood and urine contained large amounts of various ceramides polyhexoside including, in particular, a ceramide tetrahexoside containing fucose. The possibility of a new form of sphingolipidosis is discussed. PMID- 6265865 TI - [The early phase of vincristine-induced neuropathy. Electrophysiological evidence of a "dying-back" phenomenon (author's transl)]. AB - Electrophysiological exploration was carried out in 12 patients before and during administration of vincristine sulphate 1,4 mg/m2 body surface area. The patients had stage III or IV lymphoreticulosarcoma and received one injection of vincristine weekly for 6 weeks. Compared with pretreatment findings, (1) motor and sensory conduction velocity, as well as delay in triceps surae H reflex remained unchanged; (2) sensory nerve amplitude and density of distal muscle electromyographic recordings rapidly decreased; (3) the amplitude of distal tendinous reflexes rapidly diminished, whereas that of the H reflex remained stable. These results being similar to those observed in experimental acrylamide toxicity, where a "dying back" hemopathy has been demonstrated, it is suggested that the neuropathy induced by vincristine in man is of the same type. PMID- 6265864 TI - [Morphological basis of peripheral neuropathies]. PMID- 6265866 TI - Mammalian tRNA genes: nucleotide sequence of rat genes for tRNAAsp, tRNAGly and tRNAGlu. AB - A cloned 2.1 kb fragment of rat DNA hybridized to purified tRNAAsp has been sequenced. The result revealed that in addition to the putative gene for tRNAAspGAU(C), the fragment contained the tRNAGlyGGA(G) and tRNAGluGAG genes. The genes for tRNAAsp, tRNAGly and tRNAGlu have the same polarity, are arranged in this order and are regularly separated by DNA regions of about 450 bp. These rat genes contain neither intervening sequences nor the CCA sequence expected in the 3'-end of the mature tRNA. As observed in lower eukaryotic tRNA genes, the 5' flanking regions of the three rat genes do not have any significant sequence homology as a regulatory element. In the 3'-flanking region, the sequences CTTTTTG and CTTTTG are present 11 bp downstream from the 3'-end of the genes for tRNAAsp and tRNAGly, respectively. The same CTTTTG sequence is repeated twice in regions 47 and 60 bp away from the tRNAGlu gene. The short T cluster common to the three genes might be the transcription termination site as in lower eukaryotic tRNA genes. PMID- 6265867 TI - Base specificity of mismatch repair in Streptococcus pneumoniae. AB - DNA sequence analysis was undertaken to investigate the structural basis of mutations showing different integration efficiencies in Streptococcus pneumoniae. Wild type, mutant and revertant sequences at two sites in the amiA locus were determined. It appears that markers which transform efficiently or inefficiently can result from single base pair changes. A low efficiency (LE) marker corresponds to a C:G to T:A change and a high efficiency (HE) marker to a G:C to T:A change. In the latter case, two mismatches, G/A and T/C, can exist at the heteroduplex stage in transformation; only T/C appears to be recognized by the hex system which controls transforming efficiencies in pneumococcus. Each of the recognized mismatches, T/G and C/A, which result from transitional change, and T/C appears to involve at least one pyrimidine. It is proposed that the mismatch repair system of S. pneumoniae is directed against mismatched pyrimidines. DNA sequence analysis also reveals that short deletions (33 or 34 bases long) behave as very high efficiency markers, confirming that deletions are not recognized by the hex system. PMID- 6265868 TI - Characterization of a cloned histone gene cluster of the newt Notophthalamus viridescens. AB - We report the cloning and characterization of a histone gene cluster of the newt Notophthalamus viridescens. Fragments containing newt histone genes were identified in whole genome Southern blots; these fragments were cloned into a bacteriophage lambda cloning vector constructed for this purpose. The positions of most of the histone genes were determined by hybridizing subcloned sea urchin histone genes to digests of the cloned newt gene cluster. The position of each gene was verified, and its polarity determined by sequencing a portion of each. The order of the genes in the cloned segment is H1-H3-H2B-H2A-H4, with each of the genes but H2B being transcribed in the same direction. Subcloned segments of the histone gene repeat were used to determine the size of each newt oocyte histone mRNA. PMID- 6265869 TI - The organization of the histone genes in the genome of Xenopus laevis. AB - We have studied the organization of the histone genes in the DNA from several individuals of Xenopus laevis. For that purpose, Southern blots of genomic DNA, that was digested with several restriction enzymes, were hybridized with radioactively labeled DNA fragments from clone X1-hi-1 (14), containing genes for Xenopus histones H2A, H2B, H3 and H4. In the DNA of all animals that were screened we found a major repeating unit of 14 kilobasepairs, which contains genes for histones H2A, H2B, H3 and H4 (H1 not tested) and is represented up to 30 times in the genome. The order of the genes in this major repeating unit is H4 - H3 - H2A - H2B. This order is different from that in the histone DNA of clone X1-hi-1, i.e. H3 - H4 - H2A - H2B. In addition to the genes in the major repeating unit, histone genes are present in unique restriction fragments in numbers that vary from one animal to another. The restriction patterns for the histone genes in these unique fragments were found to be different for all eight Xenopus individuals that were screened. The cloned Xenopus histone gene fragment X1-hi-1 represents such a unique fragment and is not present in the DNA of each single individual. The total number of genes coding for each of the nucleosomal histones is 45-50 per haploid genome. PMID- 6265871 TI - [First-tracer passage with a single-crystal gamma camera: completed assessment of left-ventricular function by determining enddiastolic volume, regional ejection fraction and %-akinetic segment (author's transl)]. AB - Determination of left ventricular (LV) enddiastolic volume (EDV) was achieved by calibration of the system (single-crystal gamma camera, equipped with a converging collimator) to a volume phantom (egg). A good correlation (r = 0.92) was found with EDV values, obtained from cineventriculography. Images, derived from enddiastole (ED) and endsystole (ES) were corrected for background by "parabolic background subtraction", which is a realistic form of background correction in view of the LV-shape. Regional ejection fraction (REF) was calculated by an electronical operation using the ejection fraction formula and these ED and ES images. REF values reflect regional or segmental LV pump function and are superior to one- or two-dimensional parameters (e.g. visual assessment of asynergy, hemiaxis shortening) since REF values include the third dimension by referring to regional volumes. In addition, per cent-akinetic segment may be replaced by REF. Results from the literature show that first-tracer passage with a single crystal gamma camera at rest (n = 534) yield equivalent results in comparison with cineventriculography. Therefore, this nuclear procedure may be routinely used. REF values complete the diagnostic parameter as yet available. PMID- 6265872 TI - T4 RNA ligase as a nucleic acid synthesis and modification reagent. AB - Oligodeoxyribonucleotides corresponding to portions of the recognition sequence and analogues thereof of the Eco RI restriction endonuclease have been synthesized using T4 RNA ligase. The successive addition of deoxyribonucleoside 3',5'-bisphosphates to preformed deoxyoligomers allowed stepwise oligodeoxyribonucleotide synthesis. Single strand deoxyoligomers were also joined to one another by the enzyme. In addition, biotin, and fluorophore tetramethylrhodamine, and hexylamine have been added to RNA via an ATP independent RNA ligase reaction using their ADP adducts as substrates. When the beta-substituent on ADP is a good leaving group, e.g. p-nitrophenol or 4 methylumbelliferol, the RNA product is the 2'-(3')-cyclicphosphate derivative. PMID- 6265870 TI - Temperature mediated variation of DNA secondary structure in (A.T) clusters; evidence by use of the oligopeptide netropsin as a structural probe. AB - The titration viscometric investigation of the multi-mode interaction of netropsin (Nt) with (A.T) clusters of NaDNA12 and NH4DNA10 has been extended to different temperatures. The position of two boundaries on the r-scale (r= [Nt]bound/[DNA-P]) with increasing temperature steadily (rI/II) or more abruptly (rO/I) shifts to lower values. For the most (A.T) rich Nt-binding sites of modes (O), (I) and (II) this observation suggests the existence of an equilibrium between different DNA secondary structures with a different translation per base pair. The mode specific changes delta L1Nt of DNA contour length as induced by one Nt molecule proved to be almost independent of temperature. Concomitant stiffening effects increase with decreasing temperature, contrary to initial expectation. Conformational variability of (A.T) clusters may represent an essential feature in specific or selective DNA-protein interaction. PMID- 6265873 TI - Synthesis of oligonucleotides on cellulose. Part II: Design and synthetic strategy to the synthesis of 22 oligodeoxynucleotides coding for gastric inhibitory polypeptide (GIP). AB - A solid-phase approach using trinucleotide building blocks and functionalized cellulose as solid support was used to synthesize the 22 oligodeoxynucleotides that constitute a totally synthetic gene coding for a 43 amino acid peptide. Gastric inhibitory Polypeptide. The overall strategy used for the design and synthesis of the oligomers is described. PMID- 6265874 TI - The application of solid phase method-synthesized oligodeoxyribonucleotides to molecular biology problems. PMID- 6265875 TI - Synthesis of a model promoter for gene expression in Escherichia coli. AB - We have synthesized a 67-membered double-stranded DNA containing putative initiation sites for transcription and translation in E. coli. Among the potential applications of this DNA are construction of artificial genes, cloning of foreign genes in E. coli, and study of structure - activity relations in promoter and ribosome binding sites. PMID- 6265877 TI - Studies on synthesis and CD properties of complementary and self-complementary deoxyoligonucleotides. AB - Two types of deoxyoligonucleotides, a nona- and two dodecamers have been synthesized as a basis of various aspects in structural and functional studies of the DNA. Using different methodological approaches highly purified deoxyoligomers were obtained and characterized by UV absorption and CD measurements. As an example the results presented are concerned with the synthesis of the following dodecanucleotide containing the recognition site of Hind III : dC-A-C-A-A-G-C-T-T G-T-G. CD properties and some structural related effects of two complementary and a selfcomplementary deoxyoligomers are described. PMID- 6265876 TI - Synthesis of the human insulin gene. Part IV. New synthetic deoxyribooligonucleotide adaptors and primer for DNA cloning and sequence analysis. AB - The chemical synthesis of four new deoxyribooligonucleotides to be used as adaptors in molecular cloning of DNA for expression studies is described. These are (i) start-adaptor, (ii) stop-adaptor, (iii) conversion adaptor to insert ribosomal binding site, and (iv) retrieving adaptor. We have also synthesized a 19-bases-long primer, 5'-TTGTAAAACGACGGCCAGT-3' to increase the speed of DNA sequence analysis and also demonstrated its application using single-stranded M13 DNa vector. PMID- 6265878 TI - Solvent extraction method used in separating the protected product of synthetic oligodeoxyribonucleotides. AB - A solvent extraction method for separating synthetic protected oligodeoxyribonucleotides was used in our laboratory based on the lipophilic property of the protecting group of 5'-OH of the oligomers. The extraction of synthetic products protected with MMTr is complete by ether or ether-chloroform (6:1 V/V) for mononucleosides, by chloroform for dinucleoside monophosphates, by dichloromethane:n-butanol (4:1 V/V) for trimer or tetramer, and is nearly complete by dichloromethane:n-butanol (2:1 V/V) for hexamer. The 5'-end phosphorylated nucleotides, oligonucleotides and their symmetrical pyrophosphates remain in water phase. The following synthetic products of protected oligodeoxyribonucleotides have been isolated with this method, all above 85% in purity: (Formula: see text). PMID- 6265879 TI - Inhibition by 2- or/and 8-substituted adenosine derivatives of adenosine deaminase and calmodulin-dependent phosphodiesterase. AB - Several 2- or/and 8-substituted adenosine derivatives were tested for their ability to inhibit the adenosine deaminase activity in hog heart and Ca++, calmodulin-dependent phosphodiesterase activity in hog brain. Among these derivatives, 2-piperidyladenosine competitively inhibited not only the adenosine deaminase activity but also the phosphodiesterase activity. Further substitution of this compound with a bulky group at 8-position, 2-piperidyl-8-(8 aminooctylamino)-adenosine, abolished its ability to inhibit the adenosine deaminase activity, but progressively increased in the ability to inhibit the phosphodiasterase activity. On the other hand, 8-monosubstituted adenosine derivatives did not inhibit the adenosine deaminase activity. PMID- 6265880 TI - A second site specific endonuclease from Thermus thermophilus 111,Tth111II. AB - A second site specific endonuclease with a novel specificity has been isolated from Thermus thermophilus strain 111 and named Tth111II. The enzyme is active at temperature up to 80 degrees C and requires Mg2+ or Mn2+ for activity. Tth111II cleaves phi X174RFDNA into 11 fragments. From the analysis of 5' terminal sequences of the phi X174RFDNA fragments produced by Tth111II action, it was concluded that Tth111II recognized the DNA sequence (See formula in text) and cleaved the sites as indicated by arrows. PMID- 6265881 TI - Synthesis and antiherpesviral activity of 5-C-substituted uracil nucleosides. AB - Reaction of 2'-deoxy-5-hydroxyuridine with some Wittig reagents gave 5 alkoxycarbonylmethyl-, 5-carbamoylmethyl-, 5-cyanomethyl-and 5-acetonyl-2' deoxyuridines. The corresponding 1-beta-D-arabinofuranosyl derivatives were prepared from 1-beta-D-arabinofuranosyl-5-hydroxymethyluracil. The latter was also converted to 1-beta-D-arabinofuranosyl-5-vinyluracil via triphenylphosphonium salt, and then to 5-(2-halogenovinyl)derivatives. Some of these compounds showed marked antiherpesviral activity in vitro. PMID- 6265882 TI - Synthesis of the 3'- and 5'-reiterated terminal sequences of Rous sarcoma virus 35S RNA. PMID- 6265884 TI - [Beta-adrenolysis and gastric function]. PMID- 6265883 TI - [Our experiences in the treatment of undifferentiated small-cell carcinoma of the lung]. PMID- 6265885 TI - [Clinical significance of pharmacological arteriography in pancreatic neoplasms (author's transl)]. PMID- 6265886 TI - The central action of salbutamol, a beta-agonist with a potential antidepressant activity. AB - The pharmacological profile of salbutamol, an agonist of beta-adrenergic receptors and a potential antidepressant drug, and its effect on the central serotonin system were studied. It was found that salbutamol either had no effect, or, at higher doses, inhibited the spontaneous activity of mice and rats; it did not influence significantly either the produced by amphetamine locomotor stimulation (in mice and rats) or amphetamine stereotype (in rats). Salbutamol while not affecting body temperature of normal mice reversed hypothermia but not ptosis induced by reserpine, and counteracted the hypothermic action of apomorphine in mice. It neither affected the spiperone-induced catalepsy nor was active in the behavioural despair test in rats. Salbutamol had no effect either, on the fenfluramine-induced hyperthermia in rabbits, on the 5-hydroxytryptophan induced head twitch reaction in mice, on the tryptamine-induced clonic convulsions of forepaw in rats on the flexor reflex in spinal rats, or on the quipazine- or fenfluramine-induced stimulation of this reflex. The above findings indicate that the pharmacological profile of salbutamol resembles that of classical imipramine-like antidepressant drugs to a very small extent and it does not affect the central serotonergic transmission. PMID- 6265887 TI - The effect of multiple imipramine administration on monoaminergic systems of the rat brain. AB - Wistar rats received imipramine (IMI) in daily single doses of 1 or 10 mg/kg ip for up to 4 weeks. They were killed after 1,2 or 4 weeks, 24 hr after the last dose of IMI. Noradrenaline (NA), dopamine (DA), serotonin (5-HT) and 5-hydroxy indoleacetic acid (5-HIAA) were assayed in the whole brain. Whole brain dopa and 5-hydroxytryptophan (5-HTP) were assayed 30 min after administration of a central decarboxylase inhibitor, 3-hydroxybenzylhydrazine (100mg/kg). Specific binding of 3H-clonidine and 3H-WB4101 to cortical membranes was tested in rats after 1 week (only 3H-clonidine binding) and 4 weeks of IMI treatment. The levels of biogenic amines did not change during the treatment; the accumulation of dopa was transiently depressed, and that of 5-HTP - transiently elevated (only after the high dose of IMI), but after 4 weeks of treatment the accumulation of both amino acids did not differ from that in control rats. After 4 weeks of treatment with the high dose of IMI the binding of both 3H-clonidine and 3H-WB4101 to specific receptors was significantly depressed. The results suggest that under the influence of chronically administered IMI transient disturbances of the synthesis of biogenic amines occur, but they disappear after a more prolonged treatment. In the course of prolonged treatment, however, the capability of binding of radioligands by kappa-adrenergic receptors diminishes, and this suggests the development of hyposensitivity of the kappa-adrenergic system. PMID- 6265888 TI - Behavioral and biochemical effects of intraventricular kainic acid. AB - Wistar rats received intraventricularly solutions of kainic acid (KA) and behavioral symptoms and changes in the brain concentrations of biogenic amines and 5-hydroxy-indole-acetic acid (5-HIAA) following the injection were observed. KA produced a characteristic behavioral syndrome dominated by episodes of "wet dog shakes" (WDS), which were most frequent after doses of 0.25-1.5 nmole, 10-25 min after the injection. Multiple injections of KA produced only negligible inhibition of the response in initial experiments, and the effect was significantly below the control level on the 6th consecutive treatment. WDS were more frequent in rats which had undergone central chemosympathectomy with 6 hydroxydopamine. Serotoninolytics did not inhibit WDS; the shakes were strongly inhibited by pretreatment with compounds inhibiting the transmission in the noradrenergic neurons, clonidine and aceperone, by a neuroleptic, spiperone, and by opiates stimulating the opiate receptor; morphine, azidomorphine and N cyclopropylmethylnorazido-morphine, but not by an opiate receptor antagonist, naloxone. KA depressed the cerebral level of norarenaline 35 min after the administration, byt 6 days after a single injection the brain levels of noradernaline and 5-HIAA were elevated. It i suggested that the catecholaminergic systems and opiate receptors play an important role in the syndrome observed, and that the syndrome resembles the syndrome of morphine abstinence. PMID- 6265889 TI - Effect of combined GABA-ergic and dopaminergic stimulation on the action of some antiepileptic drugs in pentetrazol-induced convulsions. AB - Apomorphine (up to 10 mg/kg) and amantadine (up to 100 mg/kg) did not affect pentetrazol-induced convulsions in mice. One of two GABA-ergic agonists tested, baclofen (10 mg/kg), decreased seizure susceptibility (except for the clonic phase) while another, amino-oxyacetic acid (up to 20 mg/kg) had no effect. Combined treatment was most effective in the case of baclofen (5 mg/kg) and amantadine (100 mg/kg) where number of animals with tonic seizures was decreased. Dopaminergic stimulation did not modify the action of some anticonvulsants tested. However, GABA-ergic stimulation resulted in a marked potentiation of the action of carbamazepine (10 mg/kg) and acetazolamide (20 mg/kg), being less pronounced in reference to diazepam (0 . 5 mg/kg) in lefadol (20 mg/kg). On the other hand, combined treatment with GABA-ergic and dopaminergic stimulants was shown to enhance the action of carbamazepine and acetazolamide, but not in the clonic phase. The obtained results suggest effectiveness of GABA-ergic stimulation in the case of all drugs tested and the combined treatment with GABA ergic and dopaminergic agonists in potentiating the effects of some antiepileptics. PMID- 6265890 TI - Effect of combined treatment with dopaminergic and GABA-ergic drugs on the threshold for maximal electroconvulsions in mice. AB - Aminooxyacetic acid (AOAA; 20 and 40 mg/kg), baclofen (15 and 20 mg/kg), gamma hydroxybutyric acid (GHBA; 250 mg/kg) and gamma-aminobutyric acid (GABA: 3000 mg/kg), administered intraperitoneally, increased the convulsive threshold in mice but to a relatively small degree. Bicuculline and picrotoxin were shown to reverse these anticonvulsant effects except for baclofen. Apomorphine (10 mg/kg), amantadine (100 mg/kg) and L-DOPA (62 . 5 and 125 mg/kg) potentiated the action of AOAA (20 mg/kg). Also apomorphine (5 and 10 mg/kg) and amantadine (25 and 100 mg/kg) potentiated the anticonvulsant activity of baclofen (15 mg/kg). Combined treatment with baclofen (15 mg/kg) and amantadine (100 mg/kg) resulted in about 4 fold increase in the convulsive threshold. However, the action of GABA and GHBA was poorly affected by dopaminergic agonists, amantadine even decreased the threshold in animals pretreated with these substances. The results obtained in this study suggest dopaminergic stimulation to be of importance in potentiating the anticonvulsant action of some GABA-ergic drugs. PMID- 6265891 TI - Incorporation of 14C-adenine to cyclic 3',5'-AMP of cardiac muscle in isoprenaline-induced experimental cardiomyopathy. AB - Experimental cardiomyopathy was produced by isoprenaline (2 x 80 mg/kg sc daily for 2 days). The degree of myocardial damage was evaluated histopathologically. In the damaged cardiac muscle the incorporation of 14C-adenine was impaired, the adenylate cyclase activity was diminished and the total contents of cAMP and 14C cAMP formed from intracellular 14C-adenine metabolism were reduced. No significant changes in the activity of phosphodiesterase were found. This indicates that cAMP synthesis is impaired as a result of decreased utilization of the ATP pool formed from exogenous adenine in the cardiac muscle damaged by isoprenaline. PMID- 6265893 TI - Occupational asthma: a challenge in patient management and community care. AB - Occupational exposure to irritants accounts for 2% to 15% of all cases of asthma. Most of the offending agents evoke an IgE allergic reaction, but some seem to act through pharmacologic rather than immunologic pathways. Usually, symptoms are worse during working hours and improve in the evening and over the weekend, but in some cases onset is delayed. Symptoms may persist for weeks after exposure ceases. Skin tests or serologic tests for IgE antibody are helpful in diagnosis. Bronchial challenge with the suspected agent is valuable research procedure that occasionally is clinically useful in diagnosis. Management requires the cooperation of the medical and industrial communities. It consists of identifying asthmatic workers, removing them from exposure to the affecting environment, and treating their symptoms; preventing exposure of susceptible people through preemployment screening; and setting and adhering to reasonable occupational safety standards. PMID- 6265892 TI - Do the intracellular beta adrenoreceptors exist in the rabbit auricle. AB - Propranolol introduced by a cut-end method into atrial trabeculae evoked negative inotropic response without any significant changes in basic electrical parameters. This effect was resistant to noradrenaline but not to dibutyryl cAMP. These results suggest that existence of intracellular beta adrenoreceptors involved in the control of the contraction. PMID- 6265894 TI - [Clinical trial with TRI-OM gel in pyrosis due to pregnancy (author's transl)]. PMID- 6265895 TI - [Hypoglycemia (author's transl)]. PMID- 6265896 TI - Studies on the sidedness of the human red blood cell membrane: preparation of stable azo-erythrocytes. AB - Para-diazobenzenesulfonic acid (DBSA), a non-penetrating compound, which reacts with proteins of the external surface of intact cells, was used for the preparation of AZO-erythrocytes. When coupling of p-diazobenzenesulfonic acid to human red blood cells was carried out in phosphate-buffered saline (PBS), the cells lysed within one hour, before the completion of the reaction. Elimination of sodium chloride from the reaction mixture allowed the completion of coupling by prolonging the survival of red blood cells in he diazonium salt from one hour to three hours. The survival of human erythrocytes could be further prolonged to seven hours by carrying out coupling in the presence of cyclic 3',5'-guanosine monophosphate (cGMP). Azo-erythrocytes prepared in the absence of cyclic GMP and washed free of the diazonium salt lysed in phosphate-buffered saline, but remained stable for hours in isosmotic phosphate buffers devoid of sodium chloride ions. Under identical conditions, azo-erythrocytes prepared in the presence of cyclic GMP remained stable for two days and were suited for studies on the functional and structural aspects of red blood cell membrane. PMID- 6265897 TI - Isolation of active cAMP dependent protein kinases from calf ovaries: gel electrophoresis vs. gel electrofocusing. PMID- 6265898 TI - A modified, high yield procedure for the synthesis of unlabeled and 14C-labeled 4 methylene-DL-glutamic acid. AB - This paper describes the complete chemical synthesis of 4-methylene-DL-glutamic acid from diethylmalonate, formaldehyde and diethyl acetamidomalonate. The amino acid was obtained pure following ion-exchange chromatography and/or crystallization from hot water in an overall yield of 30% based on the amount of diethylmalonate used. Several physico-chemical characteristics of the synthetic compound were determined, including ir and pmr spectra, chromatography on paper, retention time on an amino acid analyzer, pK values and melting point; all properties of the synthetic material were found to be identical to those seen with the naturally occurring L-isomer. The procedure for obtaining gram quantities of the unlabeled compound has also been modified for the synthesis of high specific activity (10.6 mCi/mol) 4-methylene-[2-14C]-DL-glutamic acid. PMID- 6265899 TI - Distribution of proviral sequences in chromatin of embryonic fibroblasts infected by Rous sarcoma virus. AB - Sheared chromatin prepared from chicken embryo fibroblasts and fibroblasts transformed by exogenous Rous sarcoma virus (Schmidt--Ruppin strain D) was separated by rate sedimentation on glycerol gradients into two components: fast migrating (heavy chromatin fraction) and slow-migrating (light chromatin fraction). DNAs extracted from these fractions were assayed for proviral sequences by molecular hybridization using DNA complementary to the viral sequences. In uninfected cells, the endogenous complementary sequences were found to be equally distributed between heavy and light fractions. However, the newly integrated exogenous proviral sequences were found mostly in the light chromatin fraction in the transformed cells. Additionally, the light fraction was more sensitive to DNase I digestion and contains more material melting at low temperatures when compared with the heavy fraction. The results show that (i) distribution of endogenous proviral sequences is independent of chromatin conformation, and (ii) most of the newly acquired exogenous sequences are integrated within the host's chromatin fraction that exhibits properties of euchromatin. Because chromatin fragmentation and fractionation is accomplished without digestion with degrading enzymes, the chromatin fractions enriched in exogenous sequences remain intact and thus are suitable for further studies. PMID- 6265900 TI - Gene duplication and transposition linked to antigenic variation in Trypanosoma brucei. AB - DNA sequence complementary to Trypanosoma brucei mRNAs coding for the synthesis of the variant-specific antigens AnTat 1.1 and AnTat 1.8 have been cloned and characterized. These sequences have been used as probes to analyze the corresponding genes in the nuclear DNA. The two genes seem to be represented in several (three to six) copies, some of which are incomplete. Transcription of one or the other of these two genes is linked to a genetic rearrangement implying duplication and transposition of the "basic" coding sequence. There is probably one additional copy of each gene, and it seems to be complete. The 3' end of each cloned sequence contains, within a 300-base-pair fragment, a genetic element that seems to be repeated and widely distributed in the genome. This repetitive sequence is variant specific. The expression-linked copy of the gene is lost in the culture (procyclic) form of the trypanosome, where the synthesis of variant specific antigens is shut down. Comparison of two different cloned populations expressing the same serotype (AnTat 1) showed that the recurrence of a given antigenic type may be accompanied by the production of the same additional copy. PMID- 6265901 TI - Phosphorylation of McArdle phosphorylase induces activity. AB - In McArdle disease, myophosphorylase deficiency, enzyme activity is absent but the presence of an altered enzyme protein can frequently be demonstrated. We have found that phosphorylation of this protein in vitro can result in catalytic activity. We studied muscle of four patients; all lacked myophosphorylase activity, but myophosphorylase protein was demonstrated by immunodiffusion or gel electrophoresis. Incubation of muscle homogenate supernatants with cyclic AMP dependent protein kinase and ATP resulted in phosphorylase activity. The activated enzyme comigrated with normal human myophosphorylase in gel electrophoresis. Incubation with [gamma-32P]ATP resulted in incorporatin of 32P into the band possessing phosphorylase activity. Activation of phosphorylase by cyclic AMP-dependent protein kinase was inhibited by antibodies to normal human myophosphorylase or by inhibitory protein to cyclic AMP-dependent protein kinase. Incubation of muscle homogenates with phosphorylase b kinase and ATP also resulted in phosphorylase activity. After the action of cyclic AMP-dependent protein kinase, the resulting activity was similar to that of phosphorylase b. However, incubation with phosphorylase kinase resulted in activity similar to that of phosphorylase a. For several reasons, it is not likely that McArdle disease is due to lack of normal phosphorylation, but restoration of activity to the mutant protein by phosphorylation may provide a clue to understanding the mechanism of this genetic defect. PMID- 6265902 TI - On the mechanism of selective inhibition of herpesvirus replication by (E)-5-(2 bromovinyl)-2'-deoxyuridine. AB - Bromovinyldeoxyuridine (BVdUrd) is a potent antiherpesvirus compound with low cytotoxicity. To gain an insight into its selectivity and mechanism of inhibition, we chemically synthesized the 5'-triphosphate of BVdUrd, BVdUTP, and tested its effect on the activities of DNA polymerases [DNA nucleotidyltransferase (DNA directed), EC 2.7.7.7] of two herpesviruses--i.e., herpes simplex virus type 1 (HSV-1) and Epstein-Barr virus (EBV)--as well as cellular DNA polymerases alpha, beta, and gamma. The effects on the DNA polymerases were determined under assay conditions optimal for the individual polymerases. We found that the BVdUTP was considerably more inhibityory to the utilization of dTTP by the HSV-1 DNA polymerase then by the cellular DNA polymerases. For instance, as little as 1 microM BVdUTP inhibited the utilization of dTTP by HSV-1 DNA polymerase 50%, whereas the same concentration inhibited the DNA polymerase alpha and the DNA polymerase beta activities only 9% and 3%, respectively. The BVdUTP inhibited DNA synthesis by competing with the natural substrate, dTTP. The Km for dTTP and the Ki for the BVdUTP of the HSV-1 DNA polymerase were 0.66 and 0.25 microM, respectively. Kinetic analyses with the DNA polymerases alpha and beta and the EBV DNA polymerase also reflected a similar difference in sensitivity between the HSV-1 enzyme and other enzymes. Increasing the concentration of either the DNA template or the enzyme in the reaction mixture did not bring about a significant change in the extent of inhibition. Preincubation of the inhibitor with the enzyme was not necessary for inhibition. Studies on time course of inhibition revealed that the compound is inhibitory even after the initiation of DNA synthesis. These studies indicate that the ability of BVdUTP to preferentially inhibit the HSV-1 DNA polymerase may contribute towards its selective inhibition of the viral DNA replication in infected cells. PMID- 6265903 TI - Relationship between glycocalicin and glycoprotein Ib of human platelets. AB - Asialoglycoprotein Ib and asialoglycocalicin have been isolated from the membranes and from the supernatant, respectively, after sonication of neuraminidase-treated platelets, by lectin affinity chromatography on peanut agglutinin. The isolated asialoglycoprotein Ib had an apparent molecular weight of 160,000 when not reduced and 150,000 when reduced, whereas the asialoglycocalicin had an apparent molecular weight of 150,000, both reduced and unreduced, on sodium dodecyl sulfate/polyacrylamide gel electrophoresis. Both preparations contained only trace amounts of impurities. The asialoglycoprotein Ib and asialoglycocalicin in both the unreduced and reduced states were separated by gel electrophoresis, radioiodinated in gel slices, and digested with trypsin, and the digests were analyzed by two-dimensional high-voltage electrophoresis and thin-layer chromatography followed by autoradiography. The tryptic peptide maps showed great similarities between glycocalicin and glycoprotein Ib, with the latter (both unreduced and reduced) containing additional peptides, supporting the idea that glycocalicin is derived from glycoprotein Ib. The unreduced glycoprotein Ib contained additional peptides compared to the reduced due to the disulfide-bond-linked beta component. There were also slight differences between unreduced and reduced glycocalicin, indicating that at least one intramolecular disulfide bond is present. PMID- 6265904 TI - Specific binding of a prokaryotic ribosomal protein to a eukaryotic ribosomal RNA: implications for evolution and autoregulation. AB - Ribosomal protein L1 from the prokaryote Escherichia coli has been shown to form a specific complex with 26S ribosomal RNA from the eukaryote Dictyostelium discoideum. The segment of Dictyostelium rRNA protected from ribonuclease digestion by L1 and the corresponding region in Dictyostelium rDNA were investigated by nucleotide sequence analysis, and an analogous section in rDNA from Xenopus laevis was identified. When the L1-specific segments from eukaryotic rRNA were compared with those from prokaryotic rRNA, striking similarities in both primary and secondary structure were apparent. These conserved features suggest a common structural basis for protein recognition and indicate that such regions became fixed at a very early stage in rRNA evolution. In addition, certain structural elements of the L1 binding sites in rRNA are also found in the initial segment of the polycistronic L11-L1 mRNA, providing support for the hypothesis that L1 participates in the regulation of ribosomal protein synthesis by specific interaction with its own mRNA. PMID- 6265905 TI - Mouse cells transformed by bovine papillomavirus contain only extrachromosomal viral DNA sequences. AB - The viral DNA sequences in mouse C127 cells transformed by bovine papillomavirus type 1 (BPV-1) virions, by full-length linear BPV-1 DNA, or by a defined transforming subgenomic DNA segment of BPV-1 were examined by reassociation kinetics and blot hybridization. In all cases, the transformed cells contained multiple copies of BPV-1 DNA, present exclusively as supercoiled or nicked circular extrachromosomal molecules or as a slowly migrating complex of circular viral DNA molecules. In the transformed cell lines established from cells transfected with full-length linear BPV-1 DNA, there was recircularization of the input DNA which in some cases resulted in the loss of the restriction site used in the linearization of the DNA. In the transformed cell lines established with the defined subgenomic segment there was circularization of the DNA accompanied by the acquisition of new sequences or duplication and rearrangement of the BPV-1 sequences. In contrast to other well-studied virus transformation systems, no integration of the BPV-1 genome into the host chromosome could be detected under conditions sensitive enough to detect 0.1-0.2 viral genome equivalent. It was concluded that maintenance of transformation may be mediated by nonintegrated viral DNA. PMID- 6265906 TI - Physical association of pyrimidine dimer DNA glycosylase and apurinic/apyrimidinic DNA endonuclease essential for repair of ultraviolet damaged DNA. AB - T4 endonuclease V [endodeoxyribonuclease (pyrimidine dimer), EC 3.1.25.1)], which is involved in repair of UV-damaged DNA, has been purified to apparent physical homogeneity. Incubation of UV-irradiated poly(dA).poly(dT) with the purified enzyme preparations resulted in production of alkali-labile apyrimidinic sites, followed by formation of nicks in the polymer. The activity to produce alkali labile sites was optimal in a relatively broad pH range (pH 6.0-8.5), whereas the activity to form nicks had a narrow optimum near pH 6.5. By performing a limited reaction with T4 endonuclease V at pH 8.5, irradiated polymer was converted to an intermediate form that carried a large number of alkali-labile sites but only a few nicks. The intermediate was used as substrate for the assay of apurinic/apyrimidinic DNA endonuclease activity [endodeoxyribonuclease (apurinic or apyrimidinic, EC 2.1.25.2]. The two activities, a pyrimidine dimer DNA glycosylase and an apurinic/apyrimidinic DNA endonuclease, were copurified and found in enzyme preparations that contained only a 16,000-dalton polypeptide. An enzyme fraction from cells infected with bacteriophage T4v1, a mutant that is sensitive to UV radiation, was defective in both glycosylase and endonuclease activities. Moreover, occurrence of an amber mutation in the denV gene caused a simultaneous loss of the two activities, and suppression of the mutation rendered both activities partially active. These results strongly suggested that a DNA glycosylase specific for pyrimidine dimers and an apurinic/apyrimidinic DNA endonuclease reside in a single polypeptide chain coded by the denV gene of bacteriophage T4. Because the two activities exhibited different thermosensitivity, it was further suggested that conformation of the active sites for these activities may be different. PMID- 6265907 TI - Mutations in the gene coding for Escherichia coli DNA topoisomerase I affect transcription and transposition. AB - Mutations in top, the structural gene for Escherichia coli DNA topoisomerase I, have been identified and mapped at 28 min on the chromosome, near cysB. Strains carrying deletions of the top gene are viable. The top mutations, however, do exert pleiotropic effects on transcription and transposition. Mutants lacking DNA topoisomerase I have a more rapid rate of induction and a higher level of catabolite-sensitive enzymes including tryptophanase and beta-galactosidase. This general activation of transcription by top mutations can be attributed to an increase in the negative superhelicity of the DNA in vivo when the topoisomerase activity is abolished. The frequency of transposition of Tn5, a transposon carrying kanamycin resistance, is decreased by a factor of 40 or more in top mutants. A direct or indirect role of the topoisomerase in transposition is discussed. The transposition frequency of Tn3, however, is not dependent on top. Based on the studies of the E. coli top mutants, it appears that the supX gene, which was originally studied in Salmonella typhimurium [Dubnau, E. & Margolin, P. (1972) Mol. Gen. Genet. 117, 91-112] is likely to be the structural gene for DNA topoisomerase I. PMID- 6265908 TI - Epidermal growth factor stimulation of ornithine decarboxylase activity in a human hepatoma cell line. AB - Epidermal growth factor (EGF) bound specifically to the human hepatoma cell line PLC/PRF/5. Treatment of these cells with nanomolar concentrations of EGF for 4-6 hr resulted in a 2- to 6-fold increase in ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) activity. 12-O-Tetradecanoylphorbol 13-acetate also produced an increase in enzyme activity in these cells and exhibited an additive effect with EGF. It did not inhibit the binding of 125I-labeled EGF to these cells. The stimulation of enzyme activity by EGF was not inhibited by cycloheximide or actinomycin D, although these agents did cause a significant decrease in enzyme levels when added without EGF. Also, colchicine, chloroquine, ammonium chloride, and methylamine, compounds that inhibit EGF degradation in various cells types, did not interfere with the ability of EGF to elevate enzyme levels in the human hepatoma cells. PMID- 6265909 TI - Heterogeneity of RNA polymerase in Bacillus subtilis: evidence for an additional sigma factor in vegetative cells. AB - Preparations of Bacillus subtilis RNA polymerase (nucleosidetriphosphate:RNA nucleotidyltransferase, EC 2.7.7.6) from vegetatively growing cells contain small amounts of an activity (B. subtilis RNA polymerase holoenzyme II) that shows a unique promoter specificity with T7 bacteriophage DNA as compared with the normal B. subtilis holoenzyme (holoenzyme I) and lacks the normal sigma subunit [Jaehning, J. A., Wiggs, J. L. & Chamberlin, M. J. (1979) Proc. Natl. Acad. Sci. USA 76, 5470-5474]. By heparin-agarose chromatography we have obtained holoenzyme II fractions that have no detectable holoenzyme I activity as judged by their failure to utilize promoter sites for holoenzyme I on any template we have tested. These fractions are far more active with B. subtilis DNA than with T7 DNA or other heterologous templates. This high degree of specificity has allowed identification of plasmids containing cloned fragments of B. subtilis DNA that bear strong promoter sites for holoenzyme II. These promoter sites are not used at all by B. subtilis RNA polymerase holoenzyme I. The specificity of holoenzyme II is dictated by a peptide of Mr 28,000 as judged by copurification of the peptide with specific holoenzyme II activity and by reconstitution of the holoenzyme II promoter specificity when the isolated peptide is added to B. subtilis core polymerase. Hence the 28,000 Mr peptide appears to be a sigma factor that determines a promoter specificity distinct from that of RNA polymerase holoenzyme I and all other known bacterial RNA polymerases. PMID- 6265910 TI - cDNA clone coding for part of a mouse H-2d major histocompatibility antigen. AB - mRNA coding for mouse major transplantation antigens of the d haplotype was partially purified, copied into double-stranded cDNA, and cloned in Escherichia coli. Clones were selected by their ability to hybridize specifically with mRNA coding for H-2K, D, or L antigens. One of these clones, pH-2d-1, carries a 1200 base-pair insert, comprising the noncoding region, including poly(A) at the 3' end and part of the coding region. A partial sequence of the latter region showed extensive homology with the known amino acid sequences of H-2Kb,Kk, and HLA-B7 antigens. From this comparison, it appears that the coding region extends from amino acid 133 in the second domain, through the third domain, to the cytoplasmic COOH-terminal region. A stretch of 24 hydrophobic or uncharged residues, located 31 amino acids from the COOH-terminal end, could represent the segment that spans the membrane. This is followed on the cytoplasmic side of the membrane by a cluster of basic amino acids and a possible phosphorylation site on a threonine residue. PMID- 6265911 TI - Preparation of azidocalmodulin: a photoaffinity label for calmodulin-binding proteins. AB - A photoaffinity label for calmodulin-binding proteins was prepared from 125I labeled calmodulin (125I-calmodulin) and methyl-4-azidobenzimidate. Azidocalmodulin containing one azido group per calmodulin retained its ability to stimulate the CA2+-sensitive phosphodiesterase purified from bovine heart muscle. The concentrations of calmodulin and azidocalmodulin required for half-maximal stimulation of phosphodiesterase activity were 170 and 230 pM, respectively. Azido-125I-calmodulin was used to photoaffinity label troponin I, myosin light chain kinase, and the Ca2+-sensitive phosphodiesterase. Formation of crosslinked complexes required the presence of Ca2+ or Mn2+ and was inhibited by excess unmodified calmodulin. The calmodulin-binding subunits all formed 1:1 complexes with calmodulin, and the molecular weights of the crosslinked products obtained with troponin I, the phosphodiesterase, and myosin light chain kinase were 43,000, 79,000, and 116,000, respectively. Photolysis experiments using azido 125I-calmodulin and bovine cerebral cortex membranes or detergent-solubilized membranes resulted in formation of a limited number of specifically labeled polypeptides. Azido-calmodulin appears to be an appropriate photoaffinity label for the identification and characterization of calmodulin-binding subunits. PMID- 6265912 TI - Expression of the denV gene of bacteriophage T4 cloned in Escherichia coli. AB - The denV gene of bacteriophage T4 has been cloned into Escherichia coli K-12 by inserting appropriate fragments of cytosine-containing T4 DNA into the Sal I site of the plasmid pBR322. The denV gene codes for an enzyme that initiates the excision repair of pyrimidine dimers produced in DNA by UV. In uvrA recA mutants, deficient in an early step in excision repair, the cloned DNA results in enhanced UV resistance that is more pronounced in stationary- than in exponential-phase cultures. The expression of the cloned DNA also results in the enhanced survival of UV-irradiated phage lambda or of a denV mutant of phage T4 and in removal of dimers from the DNA of UV-irradiated cells. PMID- 6265913 TI - Immunofluorescent staining of poly(ADP-ribose) in situ in HeLa cell chromosomes in the M phase. AB - Randomly and synchronously growing HeLa cells were tested for poly(ADP-ribose) by direct and indirect immunofluorescent antibody techniques. Fluorescence of poly(ADP-ribose) was seen only in the nuclei of intact cells when the direct immunofluorescent antibody technique was used but in both the nuclei and cytoplasm when the indirect immunofluorescent antibody technique was used; fluorescence in the cytoplasm was nonspecific. When randomly or synchronously growing HeLa cells were fixed in acetone and treated with DNase I before incubation with fluorescein-labeled antibody, intense fluorescence was observed only in the nuclei when the direct immunofluorescent staining technique was used. Addition of 3-aminobenzamide, a potent inhibitor of poly(ADP-ribose) polymerase, with the DNase I completely abolished the fluorescence in the nuclei of synchronously and randomly growing HeLa cells, except in M-phase nuclei. These results suggest that poly(ADP-ribose) can be synthesized even in the nuclei of acetone-fixed HeLa cells from "endogenous NAD+" during incubation with fluorescent antibody and also that the fluorescence of chromosomes of HeLa cells in the M phase is, in fact, due to the in situ presence of poly(ADP-ribose), not to poly(ADP-ribose) synthesized during incubation with antibody. PMID- 6265914 TI - Determination of cellular RNA concentrations by electron microscopy of R loop containing DNA. AB - R loop hybridizations and electron microscopy have been used to determine cellular RNA concentrations for cloned genes. In plasmid DNA sequence excess, all the complementary RNA is driven into R loop structures that can be assayed by electron microscopy. To determine the concentration of a particular poly(A)+ RNA, plasmid DNA crosslinked once every 2000-5000 base pairs with trioxsalen and UV light is hybridized in DNA sequence excess to various known amounts of total poly(A)+ RNA, and the R loops are stabilized by treatment with glyoxal. If necessary, excess nonhybridized RNA is removed by Sepharose 2B chromatography, which enables the visualization of less abundant transcripts. Reconstruction experiments demonstrated that electron microscopic determination of the fraction of plasmid DNA molecules containing specific RNA loops gives accurate values of specific RNA weight fractions or concentrations in the total poly(A)+ RNA populations. These methods were also used to determine the concentrations of five RNA species complementary to sequences on TRT3, a recombinant DNA plasmid containing yeast histone 2A and 2B genes and three other nonhistone genes. The methods described allow one to visualize the R loop structures for both abundant and nonabundant transcripts and to estimate concentrations of these RNA species simply by determining the fraction of DNA containing R loops. PMID- 6265915 TI - Molecular cloning and characterization of winter flounder antifreeze cDNA. AB - Double-stranded cDNA was synthesized from partially purified winter flounder antifreeze mRNA and inserted into the endonuclease Pst I site of plasmid pBR322 by the poly(dG).poly(dC) homopolymer extension technique. The recombinant plasmids wee used to transform Escherichia coli. Clones containing antifreeze cDNA inserts were identified by the hybridization-selection technique. One of the inserts, 380 nucleotides in length, was digested with endonucleases Sau3AI and HinfI, which cleaved the insert into three fragments. The nucleotide sequences of these fragments were determined. The cDNA contains the entire coding sequence for a possible antifreeze peptide, including the leader sequence. The predicted amino acid sequence is similar to but not identical to one of the known sequences of antifreeze peptide. Within the cDNA are three segments of repeating sequences. The basic repeating sequence of 11 amino acids is maintained in the amino acid sequence coded by the cDNA and in the antifreeze peptide. PMID- 6265917 TI - Orientation of histidine residues in RNase A: neutron diffraction study. AB - Difference Fourier maps have been calculated at 2.8-A resolution by using neutron diffraction data obtained from a single crystal of RNase A. The phases were derived from a model resulting from the joint refinement of x-ray and neutron data at 2.0-A and 2.8-A resolution, respectively. The orientation of histidine-48 assumed during the refinement of the x-ray model at 2.5 A was confirmed, whereas the other three histidines had to be rotated around C beta--C gamma bonds in order to agree with the neutron difference Fourier maps. In the final model, histidine-12 is clearly hydrogen bonded to the carbonyl oxygen of threonine-45 and to the oxygen of the inorganic phosphate, and histidine-119 is bonded to another oxygen of the phosphate and to the oxygen OD1 of aspartic acid-121. PMID- 6265916 TI - Molecular cloning of two fast myosin heavy chain cDNAs from chicken embryo skeletal muscle. AB - Recombinant DNA clones containing sequences for two different types of myosin heavy chain (HC) genes from chicken embryonic skeletal muscle were constructed and analyzed. Specificity of the clones for myosin HC was demonstrated by hybrid arrested translation, by hybridization to a 7.0-kb mRNA, and by comparison of DNA sequences with known amino acid sequences of rabbit skeletal muscle myosin HC. Restriction enzyme and electron-microscopic heteroduplex analysis showed the presence of two distinct but homologous cDNA sequences. Hybrid melting curves indicated that both types of sequences represent fast myosin HC sequences. PMID- 6265918 TI - Histone genes are clustered but not tandemly repeated in the chicken genome. AB - The recombinant chicken DNA library was screened for histone genes by using pSp17, a recombinant sea urchin DNA probe containing the H2a and H3 genes of Strongylocentrotus purpuratus. Three of the isolated lambda recombinants have been analyzed by restriction enzyme mapping and Southern blotting; one histone H3 gene-encoding recombinant was further analyzed by DNA sequence determination. These studies reveal that the chicken histone genes are not tandemly reiterated, but that, at the least, several histone genes are physically closely linked in a nonrepetitive arrangement within the chicken genome. The evolutionary implications of this arrangement versus that seen in Drosophila and sea urchins is discussed. PMID- 6265919 TI - Inhibition of fructose-1,6-bisphosphatase by fructose 2,6-biphosphate. AB - Fructose 2,6-bisphosphate, a known powerful stimulator of phosphofructokinase [Van Schaftingen, E., Hue, L. & Hers, H.-G. (1980) Biochem. J. 192, 897-901] was found to inhibit, at micromolar concentrations, liver and muscle fructose-1,6 biphosphate (D-fructose-1,6-bisphosphate 1-phosphohydrolase, EC 3.1.3.11). The main characteristics of this inhibition are that (i) it is much stronger at low than at high substrate concentrations, (ii) it changes the substrate saturation curve from almost hyperbolic to sigmoidal, and (iii) it is synergistic with the inhibition by AMP. This inhibition may play an important role in the stimulation of gluconeogenesis by glucagon, because this hormone is known to decrease the concentration of fructose 2,6-bisphosphate in the liver [Van Schaftingen, E., Hue, L. & Hers, H.-G. (1980) Biochem. J. 192, 887-895]. PMID- 6265921 TI - DNA breakage and closure by rat liver type 1 topoisomerase: separation of the half-reactions by using a single-stranded DNA substrate. AB - Circular single strands of bacteriophage phi X174 DNA are broken by rat liver DNA nicking-closing enzyme (type 1 topoisomerase) in low salt (50 mM KCl) at 37 degrees C, generating linear strands containing covalently bound enzyme [Been, M. D. & Champoux, J. J. (1980) Nucleic Acids Res. 8, 6129-6142]. The linear strands can be recircularized in the presence of 10 mM MgCl2 at 24 degrees C and 37 degrees C or 250 mM KCl at 24 degrees C. Recircularization is blocked when the hydroxyl group at the 5' terminus is phosphorylated. The linears generated by the nicking-closing enzyme can also be joined to other DNA fragments containing 5' hydroxyls, but not 5' phosphates. The linkage formed in both the intrastrand and interstrand reactions is stable to alkali. Reclosure of broken single strands is presumed to be analogous to the closure step that occurs durng nicking and closing cycles on duplex DNA. PMID- 6265920 TI - Regulation of collagen synthesis by ascorbic acid. AB - After prolonged exposure to ascorbate, collagen synthesis in cultured human skin fibroblasts increased approximately 8-fold with no significant change in synthesis of noncollagen protein. This effect of ascorbate appears to be unrelated to its cofactor function in collagen hydroxylation. The collagenous protein secreted in the absence of added ascorbate was normal in hydroxylysine but was mildly deficient in hydroxyproline. In parallel experiments, lysine hydroxylase (peptidyllysine, 2-oxoglutarate:oxygen 5-oxidoreductase, EC 1.14.11.4) activity increased 3-fold in response to ascorbate administration whereas proline hydroxylase (prolyl-glycyl-peptide, 2-oxoglutarate:oxygen oxidoreductase, EC 1.14.11.2) activity decreased considerably. These results suggest that collage polypeptide synthesis, posttranslational hydroxylations, and activities of the two hydroxylases are independently regulated by ascorbate. PMID- 6265922 TI - A RNA helix-destabilizing protein is a major component of Artemia salina nuclear ribonucleoproteins. AB - A major component of 30S heterogeneous nuclear ribonucleoprotein (hnRNP) particles from Artemia salina is HD40, a protein that has been characterized as a RNA helix-destabilizing protein [Marvil, D. K., Nowak, L. & Szer, W. (1980) J. Biol. Chem. 255, 6466-6472; Nowak, L., Marvil, D. K., Thomas, J. O., Boublik, M. & Szer, W. (1980) J. Biol. Chem. 255, 6473-6478]. HD40 binds to and disrupts the secondary structure of nuclear RNA fragments isolated from 30S hnRNP with a stoichiometry of one protein per 10-12 nucleotides. The addition of HD40 in excess of this ratio results in the formation of bead-like HD4-nuclear RNA complexes that are similar in properties and appearance to native 30S hnRNP particles. The heterogeneous nuclear RNA (hnRNA) in the HD40-hnRNA complexes is unstacked and unfolded to about the same extent as the RNA in the native 30S hnRNP particles. HD40 is strikingly similar in molecular weight (40,000) and amino acid composition (no cysteine, high glycine, presence of dimethylarginine, and blocked NH2 terminus) to eukaryotic hnRNP proteins isolated from many cell types. HD40 can be separated into three isoelectric species with basic pIs, which appears to be posttranslational modifications of a single polypeptide chain. PMID- 6265923 TI - Tandem termination sites in the tryptophan operon of Escherichia coli. AB - In vivo, transcription of tryptophan (trp) operon mRNA appears to terminate at a site (trp t) 36 nucleotides after the last structural gene, and efficient function at this site requires the protein factor rho. However, distal nucleotide sequences also seem to play a role in modulating termination at trp t. We report here our in vitro studies of DNA fragments carrying portions of the trp termination region. Transcription of these DNA fragments in a purified system demonstrates that RNA polymerase actually recognizes two different termination sites. Termination at the previously characterized site, trp t, is only 25% efficient, and it is unaffected by the presence of rho factor in vitro. However, addition of rho to the transcription reaction mixture reveals that termination also occurs within a region that we have designated trp t', located about 250 bases past trp t. These two sites behave independently in vitro, whether in the tandem configuration or cloned separately, and their structural features and functional characteristics are quite different. This contrasts with the observation that termination of transcription at the end of the trp operon in vivo appears to require a rho-mediated interaction between trp t and trp t'. The possible involvement of other factors and the significance of multiple termination sites is discussed. PMID- 6265924 TI - Molecular cloning of integrated simian sarcoma virus: genome organization of infectious DNA clones. AB - The integrated form of simian sarcoma virus (SSV) was molecularly cloned in the Charon 16A strain of bacteriophage lambda. In transfection analysis, the recombinant viral DNAs demonstrated the ability to transform cells in tissue culture at high efficiency. Such transformants possessed typical SSV morphology, expressed simian sarcoma associated virus (SSAV) gag gene products in the absence of virus release, and released SSV after superinfection with a type C helper virus. A physical map of the 5.8-kilobase-pair (kbp) recombinant viral DNA clone, deduced from restriction endonuclease analysis, revealed a 5.1-kbp SSV genome containing 0.55-kbp-long terminal repeats flanked by 0.45 and 0.25 kbp of contiguous host cell sequences. By R-loop analysis, the viral DNA molecule contained two regions of homology to SSAV, separated by a 1.0-kbp nonhomologous region. This SSV-specific sequence was shown to be uniquely represented within the normal cellular DNA of diverse mammalian species, including human. Our results demonstrate that this primate transforming retrovirus arose in nature by recombination of a type C helper virus and a host cellular gene. PMID- 6265925 TI - Eukaryotic translational control: adeno-associated virus protein synthesis is affected by a mutation in the adenovirus DNA-binding protein. AB - Growth of adeno-associated virus (AAV) requires expression of certain adenovirus (Ad) genes in the same cell. AAV particles contain three proteins, VP1 (Mr 85,700), VP2 (Mr 72,000), and VP3 (Mr 61,500). These proteins have overlapping peptide maps. We recently reported that AAV RNAs make up a 3'-coterminal family of overlapping molecules. We report here that the most abundant AAV mRNA, a 2.3 kilobase spliced RNA, codes for all three proteins--VP1, VP2, and VP3--when translated in an in vitro reticulocyte lysate. This shows that the AAV capsid proteins are coded by the genome sequence between map positions 48.0 and 96.0 (1 map unit is 1% of the genome or 47 base pairs). When AAV was grown in human KB cells with the Ad temperature-sensitive mutant Ad5ts125 at the nonpermissive temperature (40 degrees C), the accumulation in vivo of AAV capsid proteins VP1, VP2, and VP3 was decreased to less than 1/50th. However, normal amounts of the 2.3-kilobase mRNA were accumulated, and this RNA could be efficiently translated in an in vitro reticulocyte lysate system to yield VP1, VP2, and VP3. These experiments suggest that in infected cells control is exerted upon the AAV 2.3 kilobase mRNA at the translational level and that this control can be influenced by mutations in Ad. These Ad mutations map in the region 2 early gene for the Ad DNA-binding protein. The temperature-sensitive system that we have studied may be useful for analysis of translational control of a eukaryotic mRNA. PMID- 6265926 TI - p53 transformation-related protein: detection of an associated phosphotransferase activity. AB - Malignant cells of the mouse transformed by a variety of different agents have been found to express high levels of a 53,000 Mr phosphoprotein (designated p53). Little or no p53 can be detected in normal mouse cells. The nucleus appears to be the predominant site of p53 localization in transformed cells. p53-related antigens are also found in transformed cells of rat, hamster, rabbit, and human. In cells transformed by simian virus 40 (SV40), p53 forms a complex with SV40 tumor (t) antigen, resulting in the coprecipitation of T antigen by monoclonal p53 antibodies. Immune complexes of p53 precipitated from extracts of SV40- or methylcholanthrene-transformed cells by monoclonal p53 antibodies have protein kinase activity. This enzymatic activity is dependent upon divalent cations, utilizing Mn2+ more effectively than Mg2+. The phosphorylation of p53 in this kinase reaction has been found to involve serine and threonine, but not tyrosine residues. In view of the finding that the transforming proteins of several different oncogenic viruses have kinase activity, the association of this activity with p53 is important with regard to the possibility of a common pathway of transformation by diverse agents. PMID- 6265927 TI - Mutations that affect lamB gene expression at a posttranscriptional level. AB - We previously obtained strains of Escherichia coli in which the beginning of gene lacZ, which codes for beta-galactosidase, is replaced by the beginning of gene lamB, which codes for a maltose-inducible outer membrane protein. In some of these strains the induction (with maltose) of lamB-lacZ hybrid protein synthesis was lethal because of membrane damage resulting from an incomplete export of this protein to the outer membrane. We describe here a class of maltose-resistant mutants obtained from one such strain. Mutants in this class fail to produce the lamB-lacZ hybrid protein but retain the ability to express lacY, which is located distal to the hybrid gene. Some of the mutants carry deletions within the hybrid gene. The others carry point mutations which most probably affect the initiation of translation at the beginning of the hybrid gene. One of these is located in the sequence that codes for the presumed ribosome interaction site on the mRNA. Three others, of which two are located in the coding region (sixth codon), are believed to result in an alteration of mRNA secondary structure such that the accessibility of the ribosome interaction site is reduced. PMID- 6265928 TI - Adrenocorticotropin-like and alpha-melanotropin-like peptides in a subpopulation of human gastrin cell granules: bioassay, immunoassay, and immunocytochemical evidence. AB - Adrenocorticotropin (ACTH)-like and alpha-melanotropin (alpha-MSH)-like peptides have been localized to a subpopulation of cytoplasmic (secretory) granules of human antropyloric gastric cells and of fetal and neoplastic gastrin cells. These granules also store gastrin and belong to the electron-dense variety of gastrin cell granules. Gastrin cells also contain granules of low to medium electron density; these store only gastrin and do not react with ACTH or alpha-MSH antisera. The alpha-MSH immunoreactive peptide was shown also to display alpha MSH bioactivity by a combined immunosorbent-bioassay technique. This peptide cochromatographs with synthetic alpha-MSH in several systems and is not detected in oxyntic mucosa or in gastric muscle wall. As in the pituitary intermediate lobe, the alpha-MSH-like peptide may be formed by cleavage of ACTH-like peptides also in gastrin cells. These data provide additional evidence for local formation of ACTH/alpha-MSH-related peptides in gastrin cells and suggest a heterogenous peptide make-up of endocrine cell granules. PMID- 6265929 TI - Inducibility of spleen focus-forming virus by BrdUrd is controlled by the differentiated state of the cell. AB - All Friend cells--except thymidine kinase (ATP:thymidine 5'-phosphotransferase, EC 2.7.1.21)-deficient mutants--are highly inducible for the release of biologically active spleen focus-forming virus (SFFV) after exposure to BrdUrd. We studied SFFV production in somatic cell hybrids made between Friend leukemia cells (FLC) and cells expressing various differentiation programs. High inducibility of SFFV and release of constitutive Friend virus (FV) and SFFV are eliminated in all hybrids in which the potential for erythroid differentiation is suppressed. FV release and its induction by BrdUrd are unchanged in hybrids that maintain the expression of erythroid differentiation. PMID- 6265931 TI - All gene-sized DNA molecules in four species of hypotrichs have the same terminal sequence and an unusual 3' terminus. AB - In hypotrichous ciliates, all of the macronuclear DNA is in the form of low molecular weight molecules with an average size of approximately 2200 base pairs. Total macronuclear DNA from four hypotrichs has been shown to have inverted terminal repeats by direct sequence analysis. In Oxytricha nova, Oxytricha sp., and Stylonychia pustulata, this terminal sequence may be written as 5'-C4A4C4A4C4 ... 3'-G4T4G4T4G4T4G4T4G4 ... In Euplotes aediculatus, the sequences is similar but differs in the lengths of the duplex region (28 base pairs) and of the putative 3' extension (14 base pairs). Also in Euplotes, a second common sequence of 5 base pairs (A-A-C-T-T-T-T-G-A-A) occurs internal to the terminal repeat and a 17-base-pair heterogeneous region: 5'-C4A4C4A4C4A4C4(X)17T-T-G-A-A ... 3' G2T4G4T4G4T4G4T4G4T4G4(X)17A-A-C-T-T ... The length of the terminal repeat sequence for O. nova was confirmed in cloned macronuclear DNA molecules. PMID- 6265930 TI - Hormonal regulation of cytodifferentiation and intercellular communication in cultured granulosa cells. AB - Granulosa cells from immature hypophysectomized diethylstilbestrol-treated rats displayed pronounced intracellular and intercellular changes after 48 hr of exposure to follicle-stimulating hormone (FSH) in vitro. As determined by light and electron microscopy, most of the FSH-treated cells became highly aggregated and grew in multilayered clusters. Numerous gap junctions were seen between cells, indicating the presence of significant intercellular communication. Microvilli densely covered the surface of the hormone-stimulated cells, which contained enlarged mitochondria with convoluted cristae, characteristic of steroidogenic cells. Luteinizing hormone receptors, identified by autoradiography with 125I-labeled human chorionic gonadotropin, were mainly associated with aggregated cells, whereas single cells were usually free of the labeled hormone. Addition of a gonadotropin-releasing hormone agonist prevented the appearance of luteinizing hormone receptors and markedly impaired cyclic AMP and progesterone production, as well as the morphological changes induced by FSH. The majority of the granulosa cells grown in the absence of either hormone assumed a flattened, and smooth shape and grew primarily in monolayers. The maintenance of cellular aggregation and intercellular communication by FSH, and its inhibition by gonadotropin-releasing hormone, may play an important role in the cytodifferentiation of ovarian granulosa cells. PMID- 6265932 TI - Quiescent human diploid cells can inhibit entry into S phase in replicative nuclei in heterodikaryons. AB - Serum-deprived quiescent human diploid cells (HDC) were fused to replicative HDC, and DNA synthesis was monitored in the resulting heterodikaryons. Quiescent HDC had an inhibitory effect on DNA synthesis in replicative HDC nuclei in heterodikaryons. The timing of the inhibitory effect suggests that entry into S phase was inhibited but ongoing DNA synthesis was not inhibited in the replicative HDC nuclei. When quiescent HDC were fused to T98G human glioblastoma cells or SUSM-1 chemically transformed human cells, entry into S phase was similarly inhibited. However, when quiescent HDC were fused to simian virus 40 transformed human cells, adenovirus 5-transformed human cells, or HeLa cells, DNA synthesis was induced in the quiescent HDC nuclei. A simple hypothesis to explain these results is that quiescent HDC contain an inhibitor of entry into S phase. Transformed cells with a dominant replicative phenotype may have gained a factor that overrides the putative inhibitor, perhaps through viral transformation, whereas recessive transformed cells may ahve lost the normal inhibitory mechanism, perhaps through mutation. Senescent HDC behave like quiescent HDC in heterodikaryons formed with the same types of replicative cells, which suggest that senescent HDC and quiescent HDC share elements of a common mechanism for cessation of proliferation. PMID- 6265933 TI - Differential staining of actin in metaphase spindles with 7-nitrobenz-2-oxa-1,3 diazole-phallacidin and fluorescent DNase: is actin involved in chromosomal movement? AB - The distribution and polymerization state of actin in metaphase rat kangaroo cells was studied by fluorescence microscopy. Formaldehyde-fixed, acetone extracted cells were labeled with either of two types of actin probes. The first, 7-nitrobenz-2-oxa-1,3-diazole-phallacidin, has high affinity for F actin and does not bind monomeric G actin. The second was a conjugate of DNase I labeled with either tetramethylrhodamine or fluorescein. DNase binds with high affinity to G actin and with lesser affinity to F actin. The polymerization state of actin was deduced by comparing the fluorescence distribution of the phallacidin derivative with that of the fluorescent DNase. The results indicate that the pole-to chromosome region of the metaphase spindle contains G actin but little if any conventional F actin. F actin is found concentrated in a diffuse distribution outside the spindle region in metaphase cells and returns to the interzone area between the chromosomes by early telophase. These results exclude spindle models for chromosomal movement that require more than about five F actin filaments per chromosome, support the hypothesis that F actin is involved in force generation for cell cleavage, and are not inconsistent with the possibility that actin outside the spindle may be involved in chromosomal movement. PMID- 6265934 TI - Human cell surface glycoprotein related to cell proliferation is the receptor for transferrin. AB - A cell surface glycoprotein antigen with an apparent molecular weight of about 100,000 that is selectively expressed on proliferating cells was purified from deoxycholate-solubilized membranes of a cultured human leukemic thymus-derived (T) cell line by affinity chromatography on a monoclonal antibody-Sepharose column. A conventional xenoantiserum prepared by immunization with the affinity purified glycoprotein was found to contain antibodies against a serum component that bound tightly to cultured cells. This molecule was shown to be specifically associated with the cell surface glycoprotein purified by immunoprecipitation from lysates of cells. We have identified the serum component as transferrin and conclude that the membrane glycoprotein is the cell surface transferrin receptor. PMID- 6265935 TI - Pseudohypoparathyroidism: inheritance of deficient receptor-cyclase coupling activity. AB - Pseudohypoparathyroidism, type I (PHP-I) is an inherited disorder of primary resistance to multiple hormones that work by stimulating adenylate cyclase. In an attempt to clarify the mode of inheritance of PHP-I, we measured the activity of the N protein, a receptor-cyclase coupling component, in erythrocyte membranes. Erythrocyte N-protein activity was reduced by approximately 50% in erythrocytes of 15 PHP-I patients and was normal in 19 of their clinically normal first degree relatives. Reduced N-protein activity and the PHP-I phenotype in these families exhibited both dominant and recessive patterns of inheritance. This suggests that at least two distinct genetic loci are involved in inheritance of N-protein deficiency. In two additional families, dominant inheritance of the PHP-I phenotype was associated with normal activities of erythrocyte N protein. Thus, it appears that mutation of at least one additional genetic locus, not involving the N protein, can produce PHP-I. PMID- 6265936 TI - Differential activity of DNA methyltransferase in the life cycle of Chlamydomonas reinhardi. AB - Two molecular weight forms of DNA (cytosine-5-)-methyltransferase [S-adenosyl-L methionine:DNA (cytosine-5-)- methyltransferase, EC 2.1.1.37], both active in assays in vitro, were isolated from the green alga Chlamydomonas reinhardi at various stages of the life cycle. The enzyme with Mr 60,000 was found in vegetative cells and gametes of both male (mt-) and female (mt+) mating types. The enzyme with Mr 200,000 was specific to gametic cells and zygotes, which are the only stages at which methylation of chloroplast DNA occurs in vivo. Chloroplast DNA from gametes was shown to be methylated on both strands at most if not all methylation sites and the Mr 200,000 enzyme was shown to methylate both unmethylated and hemimethylated sites, the latter at an elevated rate. Micrococcus luteus DNA showed the same nearest-neighbor frequencies of methylation after methylation by each molecular weight component. The data suggest strongly that the Mr 200,000 enzyme is the active multimeric form of the Mr 60,000 enzyme and that it acts as both initiation and maintenance methylase. It is proposed that methylation of chloroplast DNA in female gametes and zygotes is regulated by assembly of the multimeric Mr 200,000 active enzyme, which in turm determines the maternal inheritance of chloroplast DNA. PMID- 6265937 TI - An unusual symmetric recombinant between adenovirus type 12 DNA and human cell DNA. AB - On purification of human adenovirus type 12 (Ad12) by equilibrium sedimentation in CsCl density gradients, two bands of particles, Ad12-3 and Ad12-3a, are observed. The particles from band Ad12-3a contain a recombinant of human host cell DNA and of Ad12 DNA. The human cell DNA sequences contain repetitive DNA recurring 200 to 500 times in cellular DNA. Ad12 DNA and the recombinant genomes exhibit the same or similar lengths. This finding suggests that a constant amount of DNA is packaged into complete Ad12 particles. On cleavage of KB cellular DNA with EcoRI, BamHI, HinfI, Msp I, Mbo I Pst I, or Bgl II, the (32)P-labeled cellular DNA from Ad12-3a particles hybridizes on Southern blots to distinct bands of KB DNA. There is also less-specific background hybridization that is not observed in the control. The cellular DNA from Ad12-3a particles is not methylated, whereas the same cellular sequences in KB cell DNA appear to be extensively methylated. On denaturation and renaturation, the recombinant DNA molecules are converted to molecules half as long as Ad12 DNA, as determined by gel electrophoresis and electron microscopy. The recombinant DNA molecules were terminally labeled by exonuclease III treatment and subsequent refilling of the depleted segments with [(32)P]dNTPs by using DNA polymerase I (Klenow fragment). When these molecules were cleaved with EcoRI, BamHI, Msp I, or Pst I, only one terminal DNA fragment was found to be labeled. The results of partial digestion experiments using Msp I, HinfI, or Mbo I are consistent with a model in which 700 1150 base pairs from the left terminus of Ad12 DNA are linked to host cell DNA containing repetitious sequences, and this structure is symmetrically duplicated as a large inverted repeat of the type ABCDD'C'B'A'. The Ad12 DNA sequences are flanking the entire molecule, which consists mainly of human KB cell DNA. The recombinants appear to be stable on serial passage of the virus preparation for many years, although variations in the sequence of the recombinants occur. These symmetric recombinant (SYREC) molecules suggest a way to use adenovirus DNA as a eukaryotic vector. Their occurrence provides further evidence for the generation of virus-host DNA recombinants and may help elucidate the role this interaction may have in adenovirus replication and oncogenesis. PMID- 6265939 TI - Monoclonal antibodies to the thyrotropin receptor: implications for receptor structure and the action of autoantibodies in Graves disease. AB - Hybridoma cells have been obtained by fusing P3-NS1/1-Ag4-1 mouse myeloma cells with spleen cells from mice immunized with solubilized preparations of the thyrotropin receptor. Five clones were produced that secrete a monoclonal antibody whose binding to thyroid membranes is specifically inhibited by unlabeled thyrotropin. The antibody interacts with functioning thyroid cells in culture but not with nonfunctioning cells; this interaction is prevented by thyrotropin. The antibodies are capable of competitively blocking thyrotropin binding to bovine thyroid membrane preparations; they prevent 125I-labeled thyrotropin binding to a solubilized preparation of the glycoprotein component of the bovine thyrotropin receptor but are unable to inhibit 125I-labeled thyrotropin binding to liposomes containing gangliosides at comparable concentrations. They prevent 125I-labeled thyrotropin binding to rat, bovine, or human (Graves disease) thyroid membrane preparations. They do not stimulate adenylate cyclase activity in thyroid membrane preparations but can inhibit thyrotropin-stimulated iodide uptake by functioning thyroid cells in culture. PMID- 6265938 TI - Dissection of distinct human immunoregulatory T-cell subsets by a monoclonal antibody recognizing a cell surface antigen with wide tissue distribution. AB - A monoclonal antibody, PVR-11, was obtained after hybridization of X63Ag8.653 murine myeloma cells with spleen cells from a mouse immunized with human lymphocytes. It recognizes a 175,000- to 185,000-dalton surface antigen present on approximately 80% of normal human peripheral T lymphocytes, 50% of non-T non-B cells, and less than 10% of B cells as determined by complement-dependent microcytotoxicity. It is also present on various leukemia T cells, on some but not all T lymphoblastoid cell lines, and on a small fraction of some B lymphoblastoid cell lines. Some B-cell chronic lymphocytic leukemia cells also express the PVR-11 antigen. Functional analysis of normal human T lymphocytes demonstrated that the PVR-11-depleted T-cell subset contains the precursors of both cytotoxic and suppressor cells but lacks helper cells. On the other hand, cytotoxic effector T cells express the PVR-11 antigen. These results demonstrate that antigenic determinants with relatively wide tissue distribution can dissect functionally distinct human immunoregulatory T-cell subsets. PMID- 6265940 TI - Selective growth in serum-free hormone-supplemented medium of tumor cells obtained by biopsy from patients with small cell carcinoma of the lung. AB - Fifteen tumor-containing specimens were obtained directly from patients with small cell carcinoma of the lung and tested for their ability to grow in serum supplemented medium and in serum-free medium supplemented with hydrocortisone, insulin, transferrin, estrogen, and selenium (HITES). The tumor cells replicated in 14 of 15 cases (93%) in the HITES medium and in 10 of 15 cases (67%) in the serum-supplemented medium. The neoplastic origin of the cells growing in the HITES medium was confirmed by standard cytologic criteria, by DNA content analysis using flow cytometry, and by their ability to form colonies in agarose and tumors in athymic nude mice. While the tumor cells had very similar morphologies in both media, the serum-free medium did not support the growth of nonmalignant stromal cells, and essentially pure cultures of replicating tumor cells were obtained 7-10 days after plating. The selectivity of the HITES medium was demonstrated by the failure of cells to grow in 20 specimens cytologically negative for small cell carcinoma and in 9 of 10 specimens containing other tumor types (including other types of lung cancer). The results demonstrate that a chemically defined medium, determined by work on tissue culture-adapted human tumor lines, can support the selective growth of tumor specimens obtained directly from patients. Such selective formulas are probably specific for different tumor types and thus could be used for diagnosis, drug sensitivity testing in vitro, and identification of factors regulating tumor growth. All of these have direct application to patient treatment. PMID- 6265941 TI - Distinct pharmacological properties of excitatory amino acid receptors in the rat striatum: study by Na+ efflux assay. AB - Specific 22Na+ efflux rates from preloaded rat striatal slices are increased in a dose-dependent manner by L-glutamate and other excitatory amino acids displaying the following order of efficiency: N-methyl-D-aspartate greater than DL homocysteate greater than quisqualate greater than kainate greater than D glutamate greater than L-glutamate greater than L-aspartate. Amino acid antagonists such as 2-amino-5-phosphonovalerate, gamma-D-glutamylglycine, DL aminosuberate, DL-aminoadipate, and diethyl glutamate but not nonexcitatory amino acids such as gamma-aminobutyric acid inhibit the amino acid-induced increase in specific 22Na+ efflux rate. Increased K+ concentrations, in the presence of 2 mM Ca2+, increase the specific 22Na+ efflux. The latter and the response to N-methyl D-aspartate, but not the responses to L-glutamate, L-aspartate, quisqualate, and kainate, are inhibited to similar extents by the same antagonists. These results suggest the release from striatal nerve terminals of a putative neurotransmitter with pharmacological properties different from those of L-glutamate or L aspartate but similar to those of N-methyl-D-aspartate. The results of this study show that the stimulation of the 22Na+ efflux in brain slices by neuroactive amino acids and K+ ions is a valid and powerful tool for pharmacological investigations of excitatory amino acid receptors and their putative ligands. PMID- 6265942 TI - Adenosine receptors and behavioral actions of methylxanthines. AB - Central stimulant actions of 10 methylxanthines in mice correlate with affinities for adenosine receptors labeled with N6-[3H]cyclohexyladenosine. Affinities of methylxanthines for adenosine receptors are consonant with central levels attained at behaviorally effective doses. The much higher concentrations of methylxanthines required to influence benzodiazepine receptor binding do not correlate with behavioral potency. N6-(L-Phenylisopropyl)adenosine (L-PIA), a metabolically stable analog of adenosine with high affinity for adenosine receptors, is an extremely potent behavioral depressant, reducing locomotor activity of mice at doses as little as 0.05 mumol/kg. The D isomer, which has much less affinity for adenosine receptors, is much less active as a central depressant. Theophylline stimulates locomotor activity and reverses depressant effects of L-PIA. Caffeine or 1,7-dimethylxanthine, when administered alone, elicits biphasic effects, with locomotor depression at lower doses and stimulation at higher doses. When administered with L-PIA, even low doses of caffeine produce marked stimulation. 3-Isobutyl-1-methylxanthine given alone elicits only behavioral depression. However, like theophylline and caffeine, isobutylmethylxanthine reverses the L-PIA-evoked depression, converting it into pronounced locomotor stimulation. The data strongly suggest that the behavioral stimulant effects of methylxanthines involve a blockade of central adenosine receptors. PMID- 6265943 TI - A highly potent 3200-dalton adrenal opioid peptide that contains both a [Met]- and [Leu]enkephalin sequence. AB - A 3200-dalton adrenal enkephalin-containing peptide, designated peptide E, that exhibits high opiate activity in the guinea pig ileum longitudinal muscle preparation was purified, and its structure was determined. It contains an amino terminal [Met]enkephalin sequence and a [Leu]enkephalin sequence at the carboxyl terminus. Sequence analysis revealed that peptide E arises from a previously characterized 4900-dalton adrenal enkephalin-containing peptide. Peptide E was shown to be 30 times more potent than [Met]enkephalin in the guinea pig ileum assay, which suggests that the adrenal enkephalin-containing peptide may perform a unique biological function in vivo. PMID- 6265944 TI - Interstitial pneumonia induced by a plaque-type variant of mouse adenovirus. PMID- 6265945 TI - Effect of endotoxin administration on heart glycolytic enzyme activities in normal and diabetic dogs. PMID- 6265946 TI - Corticosteroidogenesis in vitro: effects of parathyroid hormone, ACTH, and calcium. PMID- 6265947 TI - Differential effects of barbiturates on alpha 1 and alpha 2 receptors. PMID- 6265948 TI - EEG profile of tetrahydrocannabinol seizure susceptible rabbits. PMID- 6265949 TI - The role of calmodulin in synaptic transmission. PMID- 6265950 TI - Effects of ethanol dependence on pituitary levels of ACTH and beta-endorphin in inbred mice. PMID- 6265951 TI - Sensitive biochemical methods to distinguish hormone dependent and independent Dunning tumors of prostatic origin. PMID- 6265952 TI - Effects of beta-endorphin on experimentally induced seizures in mice. PMID- 6265953 TI - Effects of growth hormone and prolactin on morphine sensitivity and tolerance. PMID- 6265954 TI - Effect of combined treatment with growth hormone and adrenocorticotropin on polyamine N-acetyltransferase activity in rat kidney. PMID- 6265956 TI - The effect of ethanol tolerance on cholesterol organization and Na+-K+-ATPase activity in rat brain membrane fractions. PMID- 6265955 TI - The effect of chronic ethanol feeding on the cAMP generating system of mouse brain. PMID- 6265957 TI - Study of a cardiotonic fraction from an extract of the seaweed. Undaria pinnatifida. PMID- 6265958 TI - An endogenous ligand to the benzodiazepine receptor: preliminary evaluation of its bioactivity. AB - Chromatographic separation of aqueous brain extracts yields a peptide containing fraction which competitively inhibits 3H-diazepam binding to its receptor. An intracerebral-ventricular injection of this isolated fraction results in altered responses in pharmacological and behavioral tests which are similar to those observed when diazepam is administered in the same fashion. The most pronounced effect was obtained in the conflict test. Changes observed in other tests, such as blocking pentylenetetrazole convulsions, altering motility or reducing hyperthermia, were also consistent with the actions of diazepam. At the dose used, neither diazepam nor the brain extract altered muscular co-ordination in two ataxia evaluations. Thus, the animals' performance in the other paradigms would not be adversely influenced by immobilization side-effects. The results reported here support the notion that an endogenous factor does exist in brain which can act like the benzodiazepine drugs when tested for bioactivity in animal studies. PMID- 6265959 TI - An analog of ACTH/MSH4-9, ORG-2766, reduces permeability of the blood-brain barrier. AB - Regional uptakes of a diffusion-limited substance, antipyrine, were compared to those of a highly diffusible substance, iodoantipyrine, in brains of conscious, unrestrained rats. The method included simultaneous measurements of regional cerebral blood flow. Within 10 min after intravenous injection of a behaviorally active analog of ACTH/MSL4-9, ORG-2766, the relative extraction of antipyrine was reduced in most regions of the brain, significantly in hypothalamus, hippocampus, parietal cortex and frontal cortex. The occipital cortex and brain stem were least affected. Since the flow of blood was not changed significantly in any region at this time, we conclude that the changes in extraction reflect a reduction in permeability of the blood-brain barrier. These results suggest that the behavioral responses to peripherally administered fragments of ACTH/MSH may depend, in part, on some action in the blood-brain barrier. These observations also suggest a mechanism by which such peptides may influence the behavioral effects of diffusion-limited drugs. PMID- 6265960 TI - Light induced interactions of benzo[a]pyrene with carboxylic acids. PMID- 6265961 TI - DNA damage in rat 9L cells treated with 8-methoxypsoralen and near-UV light assayed by viscoelastometry and S1 nuclease. PMID- 6265962 TI - Sodium channels and gating currents. PMID- 6265963 TI - Effects of ginseng saponins on the actions of adrenaline, ACTH and insulin on lipolysis and lipogenesis in adipose tissue. PMID- 6265964 TI - Studies on possible mechanisms of action of electroconvulsive therapy; effects of repeated electrically induced seizures on rat brain receptors for monoamines and other neurotransmitters. AB - There is evidence that repeated electroconvulsive shocks (ECS) in rats potentiate dopamine (DA)-, serotonin (5HT)- and alpha-noradrenergic (alpha-NA)-mediated drug induced behaviour and reduce opiate-induced behaviours. These studies suggest changes at the level of the receptor or beyond. However, high affinity in vitro 3H-ligand binding studies in brain membranes from ECS-treated control rats failed to demonstrate generalized ECS-induced changes in 5HT, DA, alpha-NA or opiate receptor binding. Binding of the beta-receptor ligand dihydroalprenolol (3H-DHA) was significantly reduced in ECS-treated rat brain membranes. This may be secondary to effects on NA neurones since ECS-induced reduction of 3H-DHA binding did not occur in animals with 6-hydroxydopamine-induced depletion of cortical noradrenaline. In conjunction with other studies, the results suggest that electroconvulsive therapy may have a noradrenergic mechanism of action. PMID- 6265965 TI - Behavioral treatment of reflex sympathetic dystrophy. PMID- 6265966 TI - The Epidemiologic Catchment Area Program of the National Institute of Mental Health. AB - We hope that the ECA Program can make a significant, and perhaps unique, contribution to the field of psychiatric epidemiology and to mental health services research. If the Program provides total true prevalence data on mental disorders according to the latest diagnostic criteria, that in itself will be a significant contribution. Such data should be of enormous benefit to those interested in etiology as well as those interested in health services research. For researchers interested in etiology, the data can be used to identify, by comparison, high-risk groups; for those interested in health services research, the results can serve as a health planning guide that does not depend on the presence or absence of treatment facilities in a given area. Incidence data will be the second major contribution of the ECA Program. Its two-wave design enhances the study of incidence, etiology, and the natural history of disorders and also allows study of the social behavior of persons entering treatment for mental disorders--a subject important to health planners. Finally, a significant result of the ECA Program may be the establishment of a viable standardized methodology for the epidemiologic study of mental disorders by means of which demonstrably replicable results can be produced. Once we demonstrate the equivalence of method and results, then the stage is set for comparative studies of all sorts. PMID- 6265968 TI - Radiation effects on cyclic AMP, cyclic GMP, and amino acid levels in the CSF of the primate. PMID- 6265967 TI - CDC's surveillance of surgical sterilization: objectives and methods of data collection. PMID- 6265969 TI - [Radiobiological characteristics for the medical proton beam with an energy of 1000 mev (author's transl)]. PMID- 6265970 TI - Immunocytochemical localization of hormones in the cell types of the adenohypophysis. AB - After a short review about the possibilities to localize immunohistochemically some adenohypophyseal hormones in light and electron microscope the author point out some actual problems of pituitary immunocytochemistry by the way of cell types studied in an in vitro system. There are demonstrated that in monolayer culture corticotrophs survive for at least 54 days. Light and electron microscope studies were made to demonstrate these hormones in the pituitary cells. PMID- 6265971 TI - Immunohistochemistry of the adenohypophysis of non-mammalian vertebrates. PMID- 6265972 TI - Auto- and heterosynthesis in pituitary corticotrophs in culture. PMID- 6265973 TI - The influence of antibrain antibodies on the level of enzyme activity and ultrastructure of brain. AB - The paper is concerned with the effect antibrain antiserum may exert on the activity of succinic dehydrogenase, glutamic dehydrogenase, cytochrome oxidase, and peroxidase. By means of quantitative cytochemistry and electron microscopy it was demonstrated that activity of succinic dehydrogenase activity or cytochrome oxidase increased in the cortex and hypothalamus following the injection of anti cortex or anti-hypothalamic serum. There were no changes of glutamic dehydrogenase and peroxidase found. Nonspecific alterations of neuronal fine structures were observed in both the cortex and the hypothalamus of rabbits treated with antiserum. PMID- 6265975 TI - [Genetic manipulation. II. The host-vector system]. PMID- 6265974 TI - [Histochemical changes in the neurosecretory hypothalamic nuclei as result of an intoxication with mercury compounds (author's transl)]. AB - The effect of experimental poisoning by organic compounds, frequently used in agriculture as fungicides, on the histochemical and histoenzymic pattern of the hypothalamic neurosecretory system has been studied. The experimental rats were fed by means of a gastric tube with the following compounds: Phenylmercuryacetate, 0.1 g daily, for 10 days; Aethylmercury-p toluenesulphanilide, 0.2 g daily, for 10 days, and Methoxyethylmercurychloride (Ceresan), 0.1 g daily, for 6 days. The histochemical and histoenzymic investigations have shown that ingestion of Phenylmercuryacetate brought about an increase in the release of antidiuretic hormone (ADH) with a concomitant enhancement of production of neurosecretory substances. The peroral administration of Aethylmercury-p-toluenesulphanilide and of Methoxyethylmercury chloride instead, resulted in the accumulation of the neurosecretion within the hypothalamic-hypophyseal system with a parallel inhibition of ADH release. The experimental poisoning of Ceresan had also a stimulatory effect on the activity of many enzymes in the neurosecretory nuclei of the rat hypothalamus. Morphological changes resulting from the experimental intoxication were only rarely observed in the neurosecretory cells of the investigated hypothalamic nuclei. PMID- 6265977 TI - Certified host vector systems. PMID- 6265976 TI - Influence of electrically induced tachyarrhythmia on the release of cyclic AMP and PGE in canine coronary sinus blood and on the level of cyclic AMP in myocardial tissue. AB - In anaesthetized open-chest dogs tachyarrhythmia (TA) was electrically induced by above-threshold stimuli via the right ventricle. During TA a significant increase in the release of PGE and cyclic AMP of 20% and 40% of the control levels, respectively, was observed in the canine coronary sinus blood (CSB), whereas the level of PGF2 alpha remained nearly unchanged under these conditions. The efflux of cyclic AMP corresponded with a concomitant increase in the left ventricular tissue level of this nucleotide by 59% during TA. Pretreatment with the beta adrenergic blocking agent propranolol (1.0 mg/kg i.v.) prevented the TA induced changes in the level of PGE as well as cyclic AMP in the CSB and in the tissue levels of cyclic AMP. Propranolol alone was without any effect on the efflux of cyclic AMP, but decreased significantly the efflux of PGE by 32%. There was an increase in the activity of phosphorylase a in the myocardial tissue from 10% to 20% of the total (a + b) activity of this enzyme during TA, which could be abolished by propranolol pretreatment. The results suggest possible interrelationships between catecholamines, cyclic AMP and PGE. PMID- 6265978 TI - An iontophoretic survey of opioid peptide actions in the rat limbic system: in search of opiate epileptogenic mechanisms. AB - Iontophoretic and micropressure drug application and lesion techniques were used to investigate the cellular source of rat limbic system epileptiform responses to opioid peptides [19]. Iontophoretically applied morphine, methionine enkephalin or beta-endorphin inhibited the spontaneous or glutamate-activated firing of the great majority of single neurons in medial and lateral septum, amygdala and cingulate cortex. These inhibitions in firing were antagonized by iontophoresis of naloxone. In contrast to inhibitory effects in other limbic areas, morphine and the opioid peptides predominantly excited CA1 and CA3 pyramidal neurons in a naloxone-sensitive manner, as previously reported [36]. On rare occasions, iontophoretically applied beta-endorphin evoked repetitive waveforms similar to interictal population EPSPs or spikes. Micropressure application of opiates and peptides also excited hippocampal neurons indicating such responses were not current-induced artefacts. The possible role of the excitatory cholinergic septal hippocampal pathway in the facilitatory response of hippocampal units to the opiates was tested with iontophoretically applied atropine and scopolamine, or lesions of septal nuclei. None of these manipulations reduced the opioid-induced excitations; rather, septal lesions enhanced excitatory and epileptiform responses to the opiates. These results support the hypothesis that opiate-evoked epileptiform activity in the limbic system arises from enhanced pyramidal cell activity in the hippocampal formation, probably by a non-cholinergic mechanism. PMID- 6265979 TI - Effects of opioid peptides on synaptic potentials in explants of rat hippocampus. AB - Bath application of 10(-8) M FK 33-824 (an enkephalin analogue) and 10(-7) M beta endorphin reversibly induced stimulus-evoked bursting activity with depolarization shifts in cultured hippocampal pyramidal cells. Statistical analysis of the data revealed that in the majority of cells, inhibitory postsynaptic potentials were markedly decreased and excitatory postsynaptic potentials increased prior to the development of bursting activity, although some inhibition persisted in cells exposed to opioid peptides. In a minority of cells, no alteration in synaptic potentials were observed to precede the stimulus-evoked bursts induced by the opioid peptides. PMID- 6265982 TI - Stimulation of the adenylate cyclase of A B16 melanoma cell line by pro opiocortin-related peptides--a structure-activity study. AB - The ability of alpha-melanotrophin (alpha-MSH or ACTH 1-acetyl-13 amide) and other structurally related peptides derived from the common precursor, pro opiocortin, to stimulate adenylate cyclase activity in a pigmented B16 mouse melanoma was investigated. The peptides ACTH 1-39, ACTH 1-24, alpha-MSH, ACTH 1 13 amide and beta-MSH all stimulated the enzyme to a similar maximal extent and with similar potency (ED50 = 1.3 . 10(-6) M) except that ACTH 1-39 was slightly less potent (ED50 = 5 . 10(-6) M). ACTH 4-10 (ED50 = 4 . 10(-5) M) and gamma-MSH (ED50 = 5 . 10(-6) M) were partial agonists. ACTH 1-10 was no more effective than ACTH 4-10 in stimulating the enzyme whereas ACTH 1-13 amide was a full agonist. The peptides beta-endorphin and its derivatives, Met-enkephalin and melanotrophin potentiating factor (MPF), failed to stimulate the enzyme. We suggest that the B16 melanoma requires not only the sequence ACTH 4-10 but also some part of the sequence ACTH 11-13, or a similar sequence in the terminal portion of beta-MSH, for full activation of the receptor-linked enzyme. PMID- 6265983 TI - [Organ transplantation and cytomegalovirus infections]. PMID- 6265980 TI - Action of gastrointestinal hormones on the myoelectric activity of the sphincter of Oddi in living rabbit. AB - The aim of this work was to compare the action of gastrointestinal (GI) hormones on the myoelectrical activity of the sphincter of Oddi. Using an experimental design previously described, we studied the electrical activity of the sphincter of Oddi and compared the percentage variation in the number of spikes before and after injection of hormones. Increasing doses of the following hormones were injected i.v. at random: CCK, OP-CCK, caerulein, bombesin, gastrin, secretin and glucagon. CCK and caerulein (as previously found), and also bombesin, OP-CCK and gastrin increased the spikes activity of the sphincter of Oddi. Secretin had no effect and glucagon decreased this activity. There was no tachyphylaxis, but a good dose-effect relationship for each hormone. Compared on a molar basis caerulein is 8 times more effective than CCK and OP-CCK which in turn are more potent than bombesin. Gastrin acts only at pharmacological doses. PMID- 6265984 TI - [Glucagonoma]. PMID- 6265981 TI - Involvement of mu-receptors in the opioid-induced generation of bursting discharges in hippocampal pyramidal cells. AB - Cultured hippocampal pyramidal cells responded to field stimulation with a short latency excitation followed by a long-lasting inhibition. This sequence was transformed into a bursting response by bath application of 10(-8) M FK 33-824, 10(-6) M (D-Ala)2(D-Leu)5-enkephalin and 10(-5) M bremazocine. Bremazocine and ethylketocyclazocine stereospecifically blocked the effects of FK 33-824. The results indicate that the excitatory responses were predominantly mediated by mu receptors. PMID- 6265985 TI - [Growth of children in Abidjan]. PMID- 6265986 TI - [Insulinomas and hyperinsulinism]. PMID- 6265987 TI - Virus exposure diminishes beta-adrenergic response in human leukocytes. AB - We used Ficoll-Hypaque isolated peripheral lymphocytes and PMNs to investigate the relationship between viral exposure and beta-adrenergic responses in target cells. Lymphocyte E-rosette formation with sheep red blood cells and PMN beta glucuronidase release in response to opsonized zymosan particles are two cell activities regulated by beta-adrenergic agonists. After incubation with influenza or measles virus, the treated cells have decreased response to isoproterenol, a beta-adrenergic agonist. The in vitro viral exposure causes a decreased beta adrenergic response in target cells. PMID- 6265988 TI - Dihydroergocryptine: a "pseudo-irreversible" alpha-adrenergic antagonist in the guinea pig vas deferens. AB - The ergot alkaloid, dihydroergocryptine, exhibits some of the characteristics of a competitive alpha-adrenergic antagonist. Dihydroergocryptine physiological antagonism is surmountable by high concentrations of alpha-adrenergic agonists and [3H]-dihydroergocryptine readily binds and dissociates from crude membranes with the characteristics expected of an alpha-adrenoreceptor ligand. However, during physiological studies, dihydroergocryptine antagonism is not readily reversible by washing. To explain this apparently paradoxical behavior of dihydroergocryptine, the characteristic of [3H]-dihydroergocryptine accumulation and efflux in the guinea pig vas deferens were studied. Vas deferens segments accumulated 0.99 pmol [3H]-dihydroergocryptine/mg protein. Most of the radioligand was extractable by acid-ethanol. About 5-6% of the radioligand remained bound to extracted tissue residues and appeared to be associated with crude membrane fractions prepared from vas deferens segments. Kinetic analysis of [3H]-dihydroergocryptine efflux from vas deferens segments indicated the presence of three compartments of radioligand in this tissue. A large compartment of [3H] dihydroergocryptine emptied slowly and may represent radioligand accumulated into the intracellular space. [3H]-Dihydroergocryptine also was released from a compartment which exhibited the size and kinetics characteristic of alpha adrenoreceptor sites on guinea pig vas deferens crude membranes. A small compartment of [3H]-dihydroergocryptine was nonexchangeable and nonextractable by acid-ethanol; this nonextractable radioligand may be bound covalently to membrane sites and/or other tissue components. PMID- 6265990 TI - The effect of hypothermia on biochemical and morphological aspects of carbon tetrachloride hepatotoxicity. AB - The temporal relationships among selected correlates of hepatocellular damage were investigated in cordotomized, hypothermic rats intoxicated with carbon tetrachloride (CCl4). Rats were spinally transected between C6 and C7 and allowed to become hypothermic. CCl4 (1.25 ml/kg ip) was administered as a 1:1 solution in corn oil. Plasma alanine aminotransferase (ALT) activity and bilirubin concentrations, hepatic malondialdehyde (MDA) formation, glucose-6-phosphatase (G6Pase) activity, and microsomal diene conjugations, as well as morphological changes were monitored over a 48 h time course. Diene conjugation, ALT and morphologic changes were all delayed and attenuated in CCl4 treated transected rats. The depression of hepatic G6Pase after CCl4 treatment was of the same magnitude in both transected and nontransected rats and was delayed only slightly in the cordotomized animals. Elevation of plasma bilirubin was delayed in transected rats, but the magnitude of the response was greater than that seen in nontransected rats. Parallel increases in MDA occurred in both CCl4 and corn oil treated transected rats over the 48 h period. These results demonstrate that spinal cord transection had differential influences upon the developing hepatotoxic effects of CCl4. PMID- 6265989 TI - Beta-adrenergic receptors of human polymorphonuclear leukocytes. AB - 125I-iodohydroxybenzylpindolol (IHYP) is a beta-adrenergic antagonist used as a ligand for the characterization of beta-adrenergic receptors in various cell preparations. Since IHYP may be adsorbed to surfaces such as test tubes and pipet tips, it is necessary to measure the actual free concentration of IHYP in the incubation solution. With this modification, the number of beta-adrenergic receptors in human peripheral PMNs can be determined with greater precision. PMID- 6265991 TI - Phosphodiesterase activity in muscles of control and dystrophic mice. AB - Cyclic AMP and cyclic GMP phosphodiesterase activity was determined in the heart and in nine skeletal muscles of control and dystrophic Re 129/J male and female mice. Phosphodiesterase activity in the presence of 0.5 mM cyclic AMP of cyclic GMP was increased in all the muscle but the heart of dystrophic mice. PMID- 6265993 TI - Sites of release of airborne foot-and-mouth disease virus from infected pigs. AB - Pigs infected with foot-and-mouth disease virus by different routes of exposure were air-sampled individually, first as 'intact' (I-) pigs and then as 'intubated' (T-) pigs, using an endotracheal tube. Irrespective of the route of infection it was found that during the early stages of disease more virus was recovered from I-pigs than from T-pigs. Most of the virus from I-pigs during incubation and early disease was associated with large and medium sized particles. T-pigs infected by direct or indirect contact excreted a range of particle sizes at this time but T-pigs infected by inoculation only excreted small particles. During advanced disease all sizes of particle were excreted by I and T-pigs. Greater amount of airborne virus were recovered at this time from I pigs than T-pigs infected by indirect contact but I-pigs infected by intravenous or intradermal inoculation excreted less infectivity than T-pigs. The results show that the respiratory tract is involved during the early stages of foot-and mouth disease in pigs infected by either natural or experimental routes of exposure and suggest that upper respiratory infection precedes lower. PMID- 6265992 TI - Sendai virus in nude and germ-free rats. AB - The pathogenesis of Sendai virus infection was studied in athymic and AGUS rats. The infection was more severe in the athymic rats and caused considerable clinical disease. Virus was shown to replicate in the bronchial epithelium and persisted in athymic rats for the duration of the experiment (32 days). The characteristic changes of necrosis of the bronchial epithelium and subsequent hyperplasia also persisted in this group and was accompanied by quite extensive interstitial pneumonitis. The virus failed to evoke an antibody response in the athymic rats. PMID- 6265994 TI - Persistence in tissues of Border disease virus antigen demonstrable by immunofluorescence. PMID- 6265995 TI - Border disease: virus persistence, antibody response and transmission studies. AB - Three groups of five and one group of four oestrus-synchronised sheep were inoculated with Border disease (BD) virus at 52 +/- 2 days after their first service. Transmission of virus to offspring as demonstrated by virus isolation, detection of viral antigen and, or antibody response occurred in 12 of 19 sheep and probably in four others which aborted or produced stillborn lambs. Both apparently normal and clinically affected animals excreted virus in saliva, urine and faeces, and excretion and contact transmission to sheep and pigs persisted for up to two and a half years. Most of the tissues of infected sheep contained virus titres between 10(3.5) and 10(5.5) TCID50 per g. The immune response in the lambs varied, in some it began before birth, in others a transient or low level response was observed in the first or second year, while others remained serologically negative for two and a half years. PMID- 6265996 TI - Early immune responses in experimental maedi. AB - Ten Finnish sheep were infected with maedi virus either by the respiratory tract or by intracerebral injection. After respiratory tract infection, virus specific lymphocyte stimulation was detected between two and seven weeks and complement fixing antibodies between seven weeks and three months. After intracerebral injection, lymphocyte stimulation was detected between five and nine weeks and complement fixing antibodies between nine weeks and four months. Neutralising antibodies were not found in six sheep killed within four months but were found in two of four sheep four and five months after infection. Virus was recovered with varying frequency from the peripheral blood leucocytes and tissues of all the sheep and also from the cerebrospinal fluid of intracerebrally inoculated sheep. The histological changes in sheep inoculated via the respiratory tract were comparable to known early maedi lesions; no changes were found in the central nervous system (CNS). The intracerebrallly inoculated sheep showed very mild periventricular inflammation in the CNS. PMID- 6265997 TI - Influence of sex hormones on the subcellular distribution of copper in sheep liver. AB - At the 14th to 16th week of pregnancy the copper content in the maternal liver was low while that in the fetus was high. After ovariectomy there was a decrease in liver copper and ceruloplasmin which was prevented by treatment with oestrogens but not with progesterone. Five groups of sheep were studied: control (barren ewes), pregnant, ovariectomised and ovariectomised treated with oestrogens or progesterone. In all, with high or low liver copper, the nuclear fraction contained the most copper. This suggests a species specificity of the copper metabolism in sheep. PMID- 6265998 TI - Murine coronaviruses: the histopathology of disease induced by intranasal inoculation. AB - Mice inoculated intranasally with murine coronaviruses (mouse hepatitis viruses) were killed daily for seven days. Lung and liver sections stained by the immunoperoxidase technique indicated that with three of the four strains examined viral localisation and replication in the lung preceded that found in the liver. Thus, infection by the respiratory route may be of importance in the transmission of these viruses. PMID- 6265999 TI - Experimental Escherichia coli and rotavirus infection in lambs. AB - Colostrum-deprived lambs were infected with either enteropathogenic Escherichia coli(O9:K30:K99) or rotavirus or a mixture of the E coli and rotavirus. E coli doses of 10(6) and above consistently produced diarrhoea, as did experimental rotavirus infection. When both of the agents were administered, the mortality rate was higher, although the duration of diarrhoea was no greater than that observed when either of the two agents was administered alone. PMID- 6266000 TI - Follow-up on angiotensin-converting enzyme in serum of patients with sarcoidosis. AB - Fluorimetrically measured serum angiotensin-converting enzyme (ACE) activity was found to be significantly elevated (p less than 0.001) in 31 untreated patients with sarcoidosis in comparison to 38 healthy controls, 20 corticosteroid-treated patients with sarcoidosis, 15 subjects with resolved sarcoidosis and 100 patients with other lung diseases. ACE values more than 2 SD above the control mean value were seen in 68% of untreated patients with sarcoidosis, but only in 5% of healthy controls, 7% of patients with tuberculosis, 0% of patients with lung tumors, 9% of patients with bronchial asthma or chronic obstructive pulmonary disease and in 17% of patients with pulmonary fibrosis due to hypersensitivity pneumonitis or diffuse idiopathic fibrosis. Resolution of sarcoidosis, spontaneously or induced by corticosteroid therapy, was accompanied by normalization of serum ACE activity in 18 out of 19 cases. In 7 out of 9 patients without clear-cut clinical improvement, changes of serum activity of ACE were not substantiated. Relapse of sarcoidosis seen in 1 case qas associated with a significant increase in ACE levels. Our results suggest that longitudinal studies of serum ACE activity are valuable in assessing the current activity and the course of sarcoidosis. Furthermore, they may contribute to restriction of necessary operative diagnostic procedures. PMID- 6266001 TI - [A case of malignant diffuse mesothelioma, bronchiolo-alveolar carcinoma and asbestosis occurred 30 years after exposure to asbestos (author's transl)]. PMID- 6266002 TI - [Anterior pituitary failure and auto-immunity]. PMID- 6266003 TI - [Plasmapheresis in the management of peripheral neuropathy in dysglobulinemia and collagen disease]. PMID- 6266004 TI - [Value and limit of clinical application of early auditory potentials in pediatrics and neurology]. PMID- 6266005 TI - [Molecular genetics and prenatal diagnosis]. PMID- 6266006 TI - [Detection, in umbilical cord blood, of antibodies against rubella virus, cytomegalovirus, herpes virus and Toxoplasma gondii]. PMID- 6266007 TI - [Bone metastasis revealing a hepatoma. 13 cases]. AB - The authors report a series of 13 cases of bony metastases leading to the discovery of a hepatoma. They were subjects of male sex, average age 64 years. Nine were severe alcoholics. The presenting symptoms were in 7 cases neurological, in four cases an isolated bone tumour, finally, one spontaneous fracture, and one case with pain alone. Severe loss of weight was frequent; in 10 cases out of 13 it was greater than 5 kg. Hepatomegaly was found in 8 cases, but in 3 cases there was no sign suggesting liver disease. In 7 cases out of nine, the metastases were already numerous at the time of diagnosis. The diagnosis of metastases from a hepatoma was made on the bone histology 11 times and from the hepatic histology in 6 cases. The histological of the bone metastasis reproduces very well that of the liver. In four cases there was local secretion of bile, in one case the metastatic liver cells underwent steatonecrosis. PMID- 6266008 TI - [Recent progress in studies of adrenergic receptors (author's transl)]. PMID- 6266009 TI - [Research on alpha-bungarotoxin and nicotinic acetylcholine receptors (author's transl)]. PMID- 6266010 TI - [The possible mechanism of the activity of cardiac pacemaker (author's transl)]. PMID- 6266011 TI - The effect of gossypol on ATPase activity of the kidney. AB - The results of the present study have shown no change in the activity of ATPase of the renal cortex of rats administered gossypol for half a year. The Na+, K+ ATPase activity of the cellular membrane of renal cortex of guinea pigs fed with gossypol for 5 or 9 weeks is significantly altered. It seems possible to diminish or to delay the inhibition by allowing the guinea pigs a potassium-rich diet ad libitum. In vitro, gossypol inhibits significantly the activity of ATPase of the brain and the kidney of rats and guinea pigs uncompetitively. However, the inhibition of the ATPase of human fetus kidney is of a mixed type. PMID- 6266012 TI - Pituitary gastrins occur in corticotrophs and melanotrophs. AB - The gut hormone gastrin was identified in pituitary cells containing adrenocorticotropic hormone and alpha-melanocyte--stimulating hormone by region specific immunocytochemistry and radioimmunoassay. Smaller amounts of gastrin were found in nerve fibers of the neural lobe and pituitary stalk. Since adrenocorticotropic hormone--like peptides occur in antropyloric gastrin cells, these data indicate a considerable similarity in peptide composition of pituitary and gastrointestinal endocrine cells and reinforces questions of multiple hormone production. PMID- 6266013 TI - Electrotonic coupling between pyramidal cells: a direct demonstration in rat hippocampal slices. AB - Intracellular recordings from pairs of neurons in slices of rat hippocampus directly demonstrated electronic coupling between CA3 pyramidal cells. When two neurons were impaled simultaneously (as verified by subsequent double staining with horseradish peroxidase), current pulses injected into one cell caused voltage changes in other cells. These interactions were bidirectional. Fast prepotentials, historically thought to represent spike activity in dendrites, resulted from action potentials in other electronically coupled pyramidal cells. These data directly demonstrate electrotonic coupling between neurons in the mammalian brain and indicate that some fast prepotentials are coupling potentials. Coupling between pyramidal cells could mediate synchronization of normal rhythmic activity and of burst discharges during seizures. PMID- 6266014 TI - Molecular and cellular mechanisms of leukocyte chemotaxis. AB - The application of modern scientific methods to the study of leukocyte function has begun to reveal the molecular and cytostructural bases of the chemotactic responses of these cells. Leukocyte chemotaxis is initiated by the binding of chemoattractants to distinct plasma membrane receptors; this finding alters transmembrane potential and activates ionic fluxes. The subsequent sequence of metabolic processes leads to a rearrangement of cytoskeletal elements that is manifested by orientation and migration of the cells toward the source of the chemotactic gradient. PMID- 6266015 TI - Fluctuating responses at a central synapse: n of binomial fit predicts number of stained presynaptic boutons. AB - Binomial predictions provided a better description than the Poisson law of fluctuating unitary inhibitory postsynaptic potentials evoked in the goldfish Mauthner cell by impulses in presynaptic interneurons. The number of terminal boutons established on this target cell by each horseradish peroxidase-filled interneuron corresponded to the value of the binomial parameter n. PMID- 6266016 TI - Hyperkeratosis induced by sunlight degradation products of the major polybrominated biphenyl in Firemaster. AB - Sunlight photodegradation of 2,2', 4,4', 5,5' -hexabromobiphenyl, the major component of Firemaster, gave a mixture that produces severe hyperkeratosis of the rabbit ear. This component in its pure state does not cause hyperkeratosis. One or more of the four major photolysis products must be responsible for this activity. A similar photodegradation pattern was observed for 2,2', 3,4,4', 5,5' heptabromobiphenyl, the second largest component of Firemaster. PMID- 6266017 TI - Opioid inhibition of dopamine release from nervous tissue of Mytilus edulis and Octopus bimaculatus. AB - Morphine and D-Ala2-Met-enkephalin as well as other opioids suppress potassium stimulated release of 3H-labeled dopamine from neurons tissue of two marine invertebrates, Mytilus edulis and Octopus bimaculatus. Naloxone reverses the inhibitory effects in both species. Potassium-stimulated release of 3H-labeled serotonin is not altered by opioids. It is postulated that opiate receptors and their endogenous effectors play a prominent role in regulation of transmitter release in invertebrates. PMID- 6266018 TI - [Pancreatic cancer. An appraisal of 147 cases (author's transl)]. AB - Out of 147 exocrine cancers of the pancreas 17 (11.6%) were considered as inoperable. Extensive lesions are frequent: liver metastasis (33%) invasion of surrounding tissues (duodenum-portal vein - mesenteric vessels) 29%, regional lymph nodes metastases (25%), peritoneal carcinomatosis (13%). For these reasons, non curative operations were the most frequent: bilio-intestinal anastomosis (56.4%), exploratory laparotomy (14.9%). Our resection rate is low: 16% (21 cases), with performance of 15 pancreatico-duodenal resections (71%), 5 total pancreatectomies (24%) and 1 left pancreatic resection. We note a mortality rate of 19%: 20% four resections, 17% after palliative anastomosis. The mean survival rate was 11.5 months following pancreatico duodenal resections and 4,8 months following anastomotic procedures. No survival after 5 years is registered. PMID- 6266019 TI - [Broncho-pulmonary complications in survivors of esophageal atresia. (author's transl)]. AB - The short term prognosis of the esophageal atresia has been improved by the progress of diagnosis and surgical techniques. The long term prognosis still depends upon the occurrence of bronchopulmonary complications. Having investigated fourteen cases and a review of the literature, the authors studied the cause of these respiratory complication. Two factors seem to play an important role: the gastroesophageal reflux and the tracheomalacia. This has important therapeutical implications: treatment of the gastro-esophageal reflux and long term respiratory kinesitherapy. The authors suggest for these patients a management plan over several years. PMID- 6266020 TI - [Maintenance therapy in cranio-facial pain: a controlled trial with tiapride (author's transl)]. AB - Tiapride, which belongs to the anisamide family, has an anti-dopaminergic effect, mainly on the mesolimbic system but also directly at the vascular level. A controlled trial was performed in 25 patients suffering from intractable migraine or facial vascular pain. Results were excellent in ten cases. Prescription of tiapride is therefore advised whenever usual therapy has failed. PMID- 6266021 TI - [Prognosis of the thyroid carcinomas after surgery (author's transl)]. AB - The authors review 140 cases and show the prime importance of the patient's age and the histological type in the prognosis of the operations of thyroid carcinoma (with the exception of solitary malignant cold nodule). The survival rate is higher with the papillary carcinoma of young patients, even though an extensive development of lymph nodes occurs, whereas metastases are encountered in the evolution of follicular carcinoma with increased risks. The anaplastic carcinoma which occurs mainly in aged people, is the worst of all. The medullary carcinoma is quite different from the others and is almost as malignant as the differentiated and anaplastic carcinomas. Surgery has to be adapted to anatomical lesions and requires the presence of an experienced histopathologist, the extension of the gland excision depending on the histological type and whether the isthmic area has been touched or not; in the same way a microscopic examination of lymph nodes, which are systematically excised, reveals whether a lymph nodes dissection has to be done at the same time. In this way extensive excisions together with their sequels can be avoided when the best prognosis can be forecasted with these lesions. PMID- 6266022 TI - [Giant lymphoid hyperplasia of mediastinum (Castleman's syndrome). Two cases (author's transl)]. AB - The authors report the cases of two patients with localized lymph node hyperplasia of angio-follicular type. One presents the plasma cell type, biological abnormalities and a shoulder-hand syndrome; the patient recovers after removal surgery. The other, of hyaline vascular type, is asymptomatic. PMID- 6266023 TI - [Renal arteriovenous fistula following percutaneous renal biopsy. Report of surgical treatment with preservation of the kidney (author's transl)]. AB - Surgical correction without parenchymal injury of a high flow renal arteriovenous fistula diagnosed 5 years after a percutaneous renal biopsy is reported. An arteriovenous fistula is elicited in 16% of all percutaneous renal biopsies. Spontaneous occlusion occurs in 50 to 70% of these cases. Persistent gross hematuria in the early stage or heart failure later may require correction of the fistula. PMID- 6266025 TI - [The diabetic's arteritis. Study of new data proved by the arteriography, the pulp biopsy and the functional explorations (author's transl)]. AB - The collation of the data supplied by the arteriography, the pulp biopsy and the "irrigraphy" (method of functional exploration founded on the rheoplethysmography) allows to distinguish three great types of arteriopathy of the diabetic patient:-high form appearing as common arteriosclerosis: occasional arteritis of the diabetics; -distal forms with special irrigraphic profile and great frequency of the microangiopathy; these forms appear very typical of the diabetes and the characteristics identified allow to give them a certain autonomy in the general setting of the arteriosclerosis. It's for these forms that the term of "diabetic arteriopathy" seems really justified; - hyperirrigation syndromes with absence of very important arterial lesion and state of distal hyperirrigation. They seem also very characteristic of diabetes but probably can be considered as beginning forms liable to develop towards a distal form. Next to this hyperirrigation syndrome, a place may be done to a relative hyperirrigation syndrome. PMID- 6266024 TI - [Hemodynamic effects of Praxinor on the peripheral circulation (author's transl)]. AB - Short-term effects of an association of two aminoalkyltheophyllines (praxinor) on blood pressure, heart rate, superficial wrist veins compliance, and blood flow in the hand, were studied after oral administration to ten subjects under resting conditions. Apart from the expected effects of blood pressure elevation and reduction in heart rate, the compliance of veins non-submitted to orthostatic constraint was lowered and drop in blood flow, mainly to the cutaneous areas was observed. The authors discuss the effects of volume distribution and blood flow modifications of general hemodynamic function. PMID- 6266026 TI - [Evaluation of cardiovascular disturbances in patients with erythrodermic skin diseases by echocardiography (author's transl)]. AB - Echocardiography was performed in seventeen patients with acute or chronic erythrodermic skin disease, to assess the cardiovascular disturbances. Fundamental difference is between the acute erythrodermic skin diseases, in which the cardiac output is low and the chronic erythrodermic skin diseases in which the cardiac output is very high, during the attacks. The reasons of this difference are studied. The ventricular function parameters are always normal and the hemodynamic disturbances seem only to be related to the modifications of the cardiac output induced by the erythrodermic skin diseases. PMID- 6266027 TI - [Serial and static brain radioangiogram in diagnosis of carotid disease: value, indication and limits by comparative study with EEG, Doppler study and cerebral arteriography (author's transl)]. AB - Value, indication and limits of serial and static brain radioangiogram in carotid disease are studied comparatively with EEG, Doppler study and cerebral arteriography. The isotopic study shows the occlusion and its consequences on middle cerebral artery and cerebral hemisphere. The "Hot-Nose" sign is rarely seen, but then with large focal abnormalities. In 20% of studied cases, isotopic study provides information about the efficiency of suppleance circulation or the existence of a blood derivation. The value of serial and static scintigraphy deserves it a better place among the non invasive diagnosis method of carotid disease. PMID- 6266028 TI - [Prevention of postoperative thrombo-embolic accidents following thoracic surgery by low-dose calcium heparinate: a comparative study (author's transl)]. AB - A comparative clinical trial was undertaken in 2420 patients undergoing thoracic surgery during a 4-year period (1973-1977); 40% of the patients had bronchial cancer. Random allocation was not considered as being possible by the surgeons and was replaced by allocation according to the time of operation. There were three protocol groups: Protocol A: First morning operations (1007 patients): subcutaneous calcium heparin, 5000 units (Ul) 2 hours and 30 minutes before surgery then every 12 hours for 15 days. Protocol B: Second morning operations (932 patients): same dose and duration of treatment; the first injection took place 24 to 72 hours after the surgical procedure. The doses were increased from the fourth day after surgery in order to obtain a moderately prolonged partial thromboplastin time (difference patient-control: 7 to 14 seconds). Protocol 0: 481 patients received no anticoagulant treatment because of a contraindication or minor surgical procedure. Preliminary results showed and increase of per operative bleeding (p less than 0.01) in treated patients; this was very well accepted by the surgeons. Among the heparin-treated patients, 11 pulmonary emboli out of 13 were observed in patients with bronchial cancer. Of these 13, 10 were fatal with 9 being verified at autopsy. The pulmonary emboli episodes occurred significantly earlier in protocol B than in protocol A. Fatal pulmonary embolism in patients with bronchial cancer was significantly more frequent in protocol B (7 cases) than in protocol A (1 case); P less than 0.01. These results have shown a low frequency of fatal pulmonary emboli in patients without bronchial cancer receiving twice-daily subcutaneous injections of heparin (2 of 1102 operated subjects). The rate was higher in patients with bronchial cancer and this results supports a recommended thrice-daily dose in such patients. In addition, the pre operative administration of heparin is useful in preventing early post-operative pulmonary embolism. PMID- 6266029 TI - [Pericarditis in adults in Abidjan. Study of one hundred observations (author's transl)]. AB - The goal of this work is to precise the respective aetiologic prevalence and the bases of diagnosis of pericarditis in Ivory Coast. The epidemiologic study has been done about 197 cases diagnosed between march 1972 and april 1978. These results are comparable to those collected previously in West Africa: the pericarditis is present in 1% of the patients admitted in the hospital and in 5.6% of the cardiovascular diseases of the unit of internal medicine in the Treichville Hospital (Abidjan). The semeiologic and evolutive study has been done with the 100 best documented records, with 90 acute and sub-acute pericarditis and 10 chronic pericarditis. The usual bases of diagnosis are used; the frequency of chest pain and signs of adiastole is emphasized. The aetiologic repartition is as follows: tuberculous 33%, septic 18%, benign acute pericarditis 15%, rheumatic 5%, uremic 13%, malignant 3%, undetermined 12%. These numbers are comparable to other author's numbers in West Africa. They confirm the important number of tuberculous and septic infections. These infections processus explain probably the frequency of constrictive pericarditis. However, the aetiology of constrictive pericarditis is often difficult to state precisely.U PMID- 6266030 TI - [Monotherapy of hypertension with a beta-blocker in a single daily dose (author's transl)]. AB - Timolol, a non selective beta-blocker was used one daily at a dosage of 10 to 20 mg, in 60 hypertensive patients with a diastolic blood pressure ranging from 100 to 120 mmHg. After 4 weeks of treatment, timolol had normalized diastolic blood pressure in 70% of patients ( less than 100 mmHg). compared to an initial treatment period with placebo (p less than 0.001). Tolerance of timolol was good, adverse clinical effects supervening in only 8% of patients (bradycardia, Raynaud's syndrome); no variation in laboratory values was observed. PMID- 6266031 TI - [Syphillis. An up-to-date physio-biological view of the main topics. II- The evolutive process of experimental syphilitic infection and a comparison with clinical symptoms in man (author's transl)]. AB - For lack of being able to grow Treponema pallidum, the only possibility that we have to study its biological behavior is to have recourse to experimentation upon animals. The stade comprising primary and secondary syphilis is characterized by visible "warning signals" which are not serious for the patient himself. But all their importance lies in the fact that they reveal the dissemination of T. pallidum inside the whole body. Thus, the healing alone or the disappearance of the lesion does not necessarily mean that it is cured. As a matter of fact, after that phase, infection may proceed "a bas bruit", as a chronic affection, which will come to light later, 10 to 15 years or more after the primary stage, as a visceral phase involving mainly cardiovascular or central nervous system. Those impairments cannot then be cured. Now, during that long period of latency, we are totally without any absolute criterion of "bacteriological sterilization", for we do not know precisely the physio-pathological meaning of these numerous serological reactions which are at out disposal and subsequently we are obliged to interpret them through divergent opinions because these techniques are not established on scientific method but are based upon empiric knowledges. PMID- 6266032 TI - [Long follow-up study of juvenile chronic arthritis (author's transl)]. AB - The authors report a follow-up study of 24 patients who initially fulfilled ARA criteria for juvenile chronic arthritis (JCA). After an evolution period of 6 to 50 years, diagnosis was revised in three patients: one suffered from mixed connective tissue disease, another from psoriatic arthropathy and the last one from Crohn's disease. Among the 21 remaining JCA patients, 16 had still an inflammatory disease when last examined and 2 of these 16 died from amyloidosis. The articular involvement appears to be similar in systemic and polyarticular disease. The physical disability can be correctly appreciated only after a 10 years evolution period. Six patients were functionally classed in grade 4. Their loss of motility was due to hip or/and knee involvement. Five of them improved after complex orthopaedic surgery and the last could not undergo anaesthesia. Both articular involvement and the fact of the chronicity of illness account for psychological and social inaptitudes. Different therapeutics are appreciated and compared. PMID- 6266033 TI - [Syphilis. An up-to-date physio-biological view of the main topics. IV.--The problem of the treatment by penicillin (author's transl)]. AB - Can penicillin be considered as an infallible treatment for syphilis? Some practitioners have hoped and even believed that this antibiotic would be able to eradicate this infection. To support their thesis, they have put forward an uniform standard therapeutic plan capable of being applied to any stage of the disease and which is based upon the following syllogism: a) all T.p. would divide every 30-33 hours. b) a level of penicillinemia of 0.03 IU/ml would destroy all Treponema when they divide. c) thus, a penicillin therapy administered 3 times giving such levels in serum during a period of 33 hours would produce a bacteriological sterilization of the infected organism. But statistics have shown that these conceptions were wrong. As a matter of fact: 1) every biological research has clearly proved that it is wrong to assert such a rhythm of division for all T.p. Since this multiplication is submitted to a succession of factors that we know more or less well, thus, during the latency phase, T.p. vegetate inside the tissues without apparently multiplying so quickly. 2) For lack of being able to cultivate T.p., it is not possible to state which is the activity level of penicillin on this germ. 3) Finally, the kinetic elimination of penicillin varies extremely, particularly depending on the drug which is used with patients, and on the localization of these germs. All experimental and clinical studies agree and insist on the fact that penicillin therapy must be given early in the infection, at a prolonged and high dose; results having to be estimated on the serological answers, especially with repeated TPI and FTA tests. As far as the late phases of the disease are concerned, for lack of being able to cultivate T. pallidum and because we do not have any absolute criterion of any bacteriological sterilization, the serological answers being often positive, circumspection has always to be a rule: it is better to admit what we do not know rather than to assert without any proof. PMID- 6266034 TI - [A familial case of thoracic outlet syndrome. Clinical, radiological study with treatment (author's transl)]. AB - The authors report the clinical and radiological study and the treatment of a fifteen members family (the two parents and their thirteen children) affected with a thoracic outlet syndrome secondary to a cervical rib and or an apophysomegaly of the seventh cervical vertebra. On the fifteen people considered, the father being deceased has not been examined but has an evocative clinical history. The mother has a clinical impairment with a late beginning and no radiological sign. Twelve children have clinical and radiological signs, one has radiological without clinical signs. Three children underwent a surgical treatment, the others only medical treatment. There is no satisfactory correlation between the clinical features and electrical investigations (electromyography, nerve conduction studies) and radiological examinations. The semiology is vascular, neurologic or mixt. Roos test seems more reliable than that of Adson, Calb and Roth, and Saunders. Eight grand-children out of fourty have been examined. Five have clinical and radiological signs, three have casual radiological signs. The radiological impairment of this family contrasts with the normal frequency of cervical anomalies in the population which is 0,12 to 1%. The family impairment of the thoracic outlet syndrome is rarely reported. PMID- 6266035 TI - [The metastatic meningoradiculitis. An exceptional detection of a gastric cancer. Review of the literature about one case (author's transl)]. AB - The authors relate a case of gastric cancer on a 47 years woman, revealed by the presence of nerve roots metastasis whose evolution was fatal in 13 months. They are pointing out the singularity of this pathology as only 29 cases have been published to date. The clinical and radiological diagnosis must cancel the existence of paraneoplasic polyradiculoneuritis, only by histological examination of the roots. The primary cancer concerns often the breast, the lungs and the stomach. But 25% of cases remain unknown. Among the various terms proposed to define this neurological complication of visceral neoplasms, the authors are selecting the expression of "metastatic meningoradiculitis", as the best reflecting of the anatomical scheme. PMID- 6266036 TI - [Adenomatoid malformation of the lung. A study on thirteen observations (author's transl)]. AB - The authors report thirteen observations of CAM of mixed solid and cystic type. They point out that besides a classic form of neonatal diagnosis might be a form late revealed in infancy or adolescence, of possible appearing after the embryonic period. This late form could be more localized. Only histologic examination can confirm the diagnosis whose fundamental criteria is the proliferation of bronchiolar or bronchiole-like structures. PMID- 6266037 TI - [Reversible acute hepatic failure after treatment with association of isoniazide rifampicin (author's transl)]. AB - One case of severe acute hepatic failure happening after surgical treatment of large tuberculous ureteral stenosis is reported. The etiology was the association of isoniazide-rifampicin; the clinical, biological and histological data of these hepatitis cases are specified; their physiopathology, as well as their treatment is studied; prevention by plasmatic evaluation of isoniazide is especially important. PMID- 6266038 TI - [Effects of chronic administration of lithium on thyroxine (T4), triiodothyronine (T3), reverse T3 (rT3) free thyroxine ratio (FTR) and thyreostimuline (TSH) in thyrotoxicosis (author's transl)]. AB - Fourteen hyperthyroid subjects were studied between 3 and 141 days. The reduction of thyrotoxicosis is rarely obtained (2 cases), mainly because on the one hand, correct plasma lithium level (0.7-1.2 mEq/L) is rarely obtained (3 cases only), on the other hand because a high dose of lithium is required, perhaps owing to high clearance of lithium in thyrotoxicosis. The indications of lithium use in thyrotoxicosis are reviewed. PMID- 6266039 TI - [A new approach to the left ventricular ejection time by systolic time intervals measurement with carotid arterial Doppler. Statistical study of correlation in one hundred and thirteen cases (author's transl)]. AB - The authors have determined systolic time intervals with carotid arterial Doppler system in a group of 113 healthy subjects. These systolic time intervals, were independent of age but strongly influenced by heart rate, and highly significant correlated with phonocardiographic and carotid arterial pulse tracings, according to the method described by Weissler. However Doppler index, no significantly correlated with heart rate, seems to us a better assessment of left ventricular performance than Weissler index. New reports on the hemodynamic determinants in healthy subjects and in patient with chronic heart failure are necessary. PMID- 6266040 TI - [Compartmentalized portal hypertension after spleno-renal shunt occlusion (author's transl)]. AB - This is a report of a patient with a thrombosed distal spleno-renal shunt with gastro-splenic disconnection and post-operative recurrent variceal hemorrhage. After portocaval shunt, a high venous pressure in the gastro-splenic sector demonstrates a compartmentalized venous hypertension. Splenectomy normalized this segmental portal hypertension, this confirming the concept that this type of portosystemic shunt is selective in early post-operative period. PMID- 6266041 TI - [Guillain-Barre syndrome following measles (author's transl]. PMID- 6266042 TI - [Seronegative systemic lupus erythematosus (author's transl)]. AB - Seronegative systemic lupus erythematosus is defined as a SLE devoided of antinuclear factors as well as of LE cells when at least 4 out of the 14 ARA criteria are present. We describe herein two case reports and review previous literature concerning this topic. This kind of SLE is characterized by a high incidence of Raynaud's disease, photosensitivity, oral ulcerations, alopecia and perhaps less frequent kidney and central nervous system involvement. The hypotheses about the absence of ANF are discussed. The awareness of such a SLE ("devoided of ANF rather than" seronegative") is to be kept in mind from a chemical, therapeutic and pathophysiologic point of view. PMID- 6266043 TI - [Thoracic pain and anomaly of the thoracic outlet (author's transl)]. PMID- 6266044 TI - [Cutaneous manifestation of pheochromocytoma. Report of a case (author's transl)]. AB - A 33 years old woman was investigated for paroxystic hypertension worsened by beta-adrenergic blocking drugs therapy. Clinical investigation revealed cutaneous abnormalities with erythemato-macular eruption on dorsalis faces of both hands. These lesions were histologically non specific with capillaritis and oedema. angiography revealed a left sided pheochromocytoma. Cutaneous abnormalities disappear after intervention. Pheochromocytoma is rarely associated with cutaneous disease: most papers describe intermittent "flush" phenomenon. Permanent lesions are non frequent: erythrocyanosis, rash with nodosities or macular lesions, restricted places of necorsis, distal necorsis, hypochromic lesions. The variability of cutaneous disease of pheochromocytoma seems reliable to the biochemical structure of catecholamine secreted by tumor. PMID- 6266045 TI - [The treatment of an anxiety - depression syndrome in young women. Report of a case (author's transl)]. AB - During treatment of an anxiety-depression syndrome, a young woman presented with amenorrhoea probably related to sulpiride administration. Interruption of treatment provoked depression relapse; the addition of bromocriptine prevented recurrence of the amenorrhoea without affecting the therapeutic results of the second course of treatment with sulpiride. PMID- 6266047 TI - [Idiopathic thrombocytopenic purpura (ITP) in childhood (author's transl)]. AB - Half of thrombocytopenic purpuras occurs after a viral infection and is cured in a few weeks, but 10% of the cases are chronic. Toxic purpura is exceptional. Most of the cases are idiopathic. At the beginning it is impossible to foresee acute or chronic evolution. No treatment is necessary in ITP without serious bleeding. Prednisone does not avoid chronic state but shortened duration of acute ITP. Dosage is 1 mg/kg/day. Continuous corticotherapy is excluded in chronic ITP. Short corticotherapy is useful during bleeding periods. Splenectomy is to be considered after 6 or 12 months. Overall success raise 75%. Splenectomy is forbidden temporarily before 5 years, and definitely in immune deficiency. Immunosuppressive drugs are rarely used in childhood. Treatment with infusion of vincristine labeled platelets is in study. During the 18 months after cure, vaccinations must be avoided. PMID- 6266048 TI - [Non discal surgical sciatic neuralgia (author's transl)]. AB - Non discal sciatic neuralgia accounts for 5 per cent of all cases of surgical sciatica. They are divided into four groups: central sciatica very seldom, cordal and root sciatica more common and truncal sciatica. These sciatica are dominated by atypical clinical features: atypical provoking factor, atypical character, atypical topography and therapy. A good x-rays study is necessary involving myelography, angiography of the spine etc., but discography and lumbar phlebography are not useful. A rapid review of aetiologies shows that they cover a wide area and that therapy must be debated for each case. PMID- 6266049 TI - Histopathology of sarcomas. PMID- 6266046 TI - [What are waiting for chemotherapy in urology (author's transl)]. AB - The place of chemotherapy inthe treatment of urological cancers remains imprecise. According to numerous publications, all urological cancers should benefit from chemotherapy. This review's goal is to point out the benefits that may be obtained with this type of treatment. Reduction of tumor volume, improvement of quality of survival, length of survival and toxic side effects are taken into account. Two different situations are considered: cases in which chemotherapy has proved to be efficient and should be prescribed, and, in most cases, situations in which chemotherapy is designed to help finding active drug and define efficient therapeutic protocols. This can only be indicated when prospective randomised studies are done in specialised centers with the collaboration of urologists and radiotherapists. PMID- 6266051 TI - The pediatric patient with sarcoma. AB - The results of the treatment of the commonest soft tissue sarcoma in childhood have improved dramatically during the past decade. The combination of reasonable surgery, radiotherapy and multiagent chemotherapy has been demonstrated to provide effective control of both the primary tumor and distant metastases in patients with rhabdomyosarcoma. Similar progress with the less common soft tissue malignancies will be more difficult to attain. Current therapeutic trends appear to favor a similar multimodal approach with a conservative but complete surgical excision combined with varying regimens of radiation and chemotherapy. Because of the infrequent occurrence of these unusual tumors (450 cases per year in the United States) no single institution can possibly attract a significant number of new cases to enter on treatment protocols. Substantial improvement in our current therapeutic techniques will be possible in the future only if our combined multicenter studies are continuously refined, re-examined, and extended. A plea is made for early referral of these difficult patients to regional study centers. PMID- 6266050 TI - Staging system for soft tissue sarcoma. PMID- 6266052 TI - Case report 141. Malignant fibrous histiocytoma associated with enchondroma of bone. PMID- 6266053 TI - Gas and metrizamide myelography in abnormalities of the craniovertebral junction. AB - Ten symptomatic patients with skeletal abnormalities of varying etiology at the craniovertebral junction were studied with gas or metrizamide myelography. The type of compressive pathology was accurately delineated by these techniques. The surgical approach was determined by the findings on the myelograms. PMID- 6266054 TI - [Hormone receptors]. PMID- 6266055 TI - Paraganglioma of the orbit - an exercise in diagnosis. A case report. AB - A case is described of a child presenting with an extremely large orbital tumour, which had an alveolar pattern on histological examination. The differential diagnosis, which included alveolar rhabdomyosarcoma, alveolar soft-part sarcoma and non-chromaffin paraganglioma, could only be made on electron microscopic examination. Exact diagnosis was important because of prognostic and therapeutic implications. The presence of neurosecretory granules in tumour cells was demonstrated on electron microscopy, confirming the diagnosis on non-chromaffin paraganglioma, a benign tumour which is extremely rare in this site. PMID- 6266057 TI - Concurrent oral and genital infection with an identical strain of herpes simplex virus type 1. Restriction endonuclease analysis. AB - The virus isolated from concurrent genital and oropharyngeal lesions of a male patient was identified as herpes simplex virus type 1 (HSV-1) by rate neutralization and biological marker tests. Analysis by digestion with restriction endonuclease revealed that isolates from the penis and anterior pillars had identical patterns, similar to those of prototype HSV-1. Data indicate that a person can be infected with the same strain of HSV-1 in two different sites at the same time. PMID- 6266056 TI - The control of peroxidase-catalysed iodination and de-iodination. AB - It has been demonstrated that the H2O2/l ratio is a critical factor in the control of iodination and de-iodination of covalently bound tyrosyl residues in proteins and free iodotyrosines by peroxidase enzymes. This has been shown for myeloperoxidase (MPO) isolated from normal human polymorphonuclear lymphocytes in particular, and also for peroxidase of animal origin such as thyroid peroxidase (TPO) and lactoperoxidase (LPO). It has been shown that the H2O2/l ratio exerts a controlling influence on MPO-catalysed reactions of fully iodinated tyrosines, e.g. di-iodotyrosine, and of partially and completely iodinated thyronines such as thyroxine and tri-iodothyronine. Using an in vivo model system it has been shown that MPO catalyses the sequential events of iodination, iodine exchange and de-iodination of tyrosines and, furthermore, that all three reactions are influenced by the rate of H2O2 generation and the iodide concentration of the reaction medium. The action of MPO on iodothyronine substrates only affects de iodination irrespective of whether the iodothyronine is partially iodinated, as in tri-iodothyronine, or completely iodinated, as in thyroxine. This MPO catalysed de-iodination of thyroxine and tri-iodothyronine can also be regulated by the H2O2/l ratio. Moreover, the results show that MPO-catalysed iodine exchange can only occur in completely iodinated tyrosines such as di-iodotyrosine (DIT). Iodine exchange in partially iodinated tyrosines such as mono-iodotyrosine (MIT) or in iodothyronines (T3 and T4) cannot be catalysed by MPO irrespective of the H2O2/l ratio. These results introduce a new concept which may be important in understanding the control of thyroid activity in thyroid disease and the control of MPO activity in biological defence mechanisms in man. PMID- 6266058 TI - Distribution of steroid hormone receptors in human soft tissue sarcomas. AB - Sixty-six human soft-tissue sarcoma specimens were assayed for incidence and distribution of steroid hormone receptors. Liposarcomas (43%) and leiomyosarcomas (60%) had a high incidence of estrogen receptor. In contrast, sarcomas of fibrous and synovial tissue origin lacked any detectable receptor for estrogen. Malignant fibrous histiocytoma had the highest incidence of glucocorticoid (66%) and androgen (66%) receptors. The incidence of receptors for estrogen and glucocorticoid was higher in female than in male patients (62% and 38%, respectively). Sucrose density gradients demonstrated 8s-type receptors for both estrogen and glucocorticoid. Data from this study suggest that specific high affinity cytosolic receptors for steroid hormones are present in human soft tissue sarcoma and that their distribution may depend on the histogenetic origin and the sex of patients. PMID- 6266059 TI - The Epstein-Barr virus in the pathogenesis of posttransplant lymphoproliferative disorders. Clinical, pathologic, and virologic correlation. AB - Twelve renal transplant patients with lymphoproliferative disorders (LPDs) were studied. Two clinical patterns were identified: (1) Young patients present with an infectious mononucleosis-like illness with fever, sore throat, and lymphadenopathy soon after transplantation or antirejection therapy. Many organs are ultimately involved, and the clinical course is one of a rapidly fatal LPD. (2) Older patients present a longer time after transplantation with symptoms of solid tumors involving the central nervous system, oropharynx, liver, or small bowel. The clinical course is slower, but it is progressive and fatal. Morphologically these LPDs can all be classified as polymorphic diffuse B-cell hyperplasia (PDBH) or polymorphic diffuse B-cell lymphoma (PBL). Cell marker studies in four patients demonstrated a polyclonal B-cell proliferation. Transition from a polyclonal B-cell proliferation to a monoclonal tumor may occur. Epstein-Barr virus (EBV) specific antibody titers, anticomplement immunofluorescence staining of tumors for the presence of the Epstein-Barr nuclear antigen (EBNA), and EBV complementary ribonucleic acid (cRNA)/deoxyribonucleic acid (DNA) hybridization and vDNA/DNA reassociation analysis implicate EBV as the probable etiologic agent in these disorders. Successful management of these lethal LPDs may depend on discontinuation of immunosuppression and removal of the allograft. Antiviral therapy, however, may prove to be useful. PMID- 6266060 TI - Thyrotropin binding and adenylate cyclase stimulation in thyroid neoplasms. AB - Experiments were performed to determine whether thyroid-stimulating hormone (TSH) receptors coupled to adenylate cyclase are present in both benign and differentiated malignant thyroid tumors, and to identify abnormalities in the TSH receptor-adenylate cyclase system in neoplastic thyroid tissue. TSH binding and adenylate cyclase assays were performed under the same in vitro cyclase conditions. 125I-bovine TSH was incubated with an 8,000 X g thyroid or thyroid tumor particulate fraction from both normal and most neoplastic tissue two receptor sites were identified. The association constant for the high-affinity receptor from normal thyroid was 10.5 +/- 3.2 nM (mean +/- standard error) with a capacity of 0.8 +/- 0.3 pM/mg particulate protein. The association constant of the high-affinity receptor found in the particulate fraction from the thyroid adenomas was 3.5 +/- 0.5 nM with a capacity of 0.4 +/- 0.1 pM/mg particulate protein; for the thyroid carcinomas the association constant was 1.4 +/- 0.3 nM and the capacity 0.2 +/- 0.1 pM/mg particulate protein. The maximum adenylate cyclase response to TSH for particulate fractions from both benign and malignant tumors was greater (P less than 0.05) than in the particulate fraction from normal adjacent thyroid tissue. There was also a positive correlation between the equilibrium constants for 125I-bTSH binding and adenylate cyclase activation suggesting that binding sites are coupled to cyclase in the neoplastic tissue and that the binding observed in these experiments is of biologic consequence. PMID- 6266061 TI - Histamine stimulation and inhibition of human cryopreserved parathyroid tissue. AB - To elucidate the mechanism by which cimetidine, an H2 antagonist, inhibits parathormone secretion, immunoreactive cyclic AMP (cAMP) production was measured at low (0.5 mM) and normal (1.0 mM) calcium concentrations, with histamine stimulation and histamine inhibition by cimetidine, in a cell dispersion preparation from cryopreserved glands of 12 hyperparathyroid patients. At low calcium, histamine-mediated cAMP production increased from a basal level of 382 +/- 44 femtomoles/10(5) cells to 514 +/- 74 femtomoles/10(5) cells (P less than 0.05). Cimetidine inhibition of histamine-stimulated parathyroid cells at low calcium resulted in a decrease in cAMP production from 514 +/- 74 femtomoles/10(5) cells to 410 +/- 62 femtomoles/10(5) cells (P less than 0.01). At normal calcium the cAMP production in the histamine-stimulated experiment increased from a basal level of 293 +/- 66 femtomoles/10(5) cells to 477 +/- 100 femtomoles/10(5) cells (P less than 0.01) and decreased to 321 +/- 69 femtomoles/10(5) cells (P less than 0.01) in the histamine and cimetidine experiment. Stimulation by isoproterenol, a beta-adrenergic agonist, at low calcium in the histamine-primed group showed an increase in cAMP production from 514 +/- 74 femtomoles/10(5) cells to 639 +/- 71 femtomoles/10(5) cells (P less than 0.005). These results suggest that histamine plays an important role in cAMP production in hyperparathyroid cells and that cimetidine inhibition of histamine stimulated cAMP production may explain the decrease of immunoreactive parathormone by this H2 antagonist reported in patients with hyperparathyroidism. PMID- 6266062 TI - [Blood levels of parathyroid hormone, calcitonin and cyclic adenosine monophosphate in diabetes mellitus]. PMID- 6266063 TI - [Bronchial asthma and bronchial reactivity]. PMID- 6266064 TI - Teratogenic effects of aliphatic nitriles. AB - Intraperitoneal injection of acrylonitrile at 1.51-2.26 mmole/kg (80-120 mg/kg) or propionitrile at 0.54-1.51 mmole/kg (30-83 mg/kg) on the morning of Day 8 of gestation in the hamster induced exencephaly, encephalocoeles, and rib fusions and bifurcations in the offspring. These doses of the aliphatic nitriles also resulted in obvious toxicity to the dams. Multiple intraperitoneal injections of sodium thiosulfate at 4.03 mmole/kg (1 gm/kg) protected both dams and embryos against toxicity. When the larger doses of either acrylonitrile or propionitrile were given in the presence of sodium thiosulfate, teratogenic effects were observed in the absence of overt signs of maternal poisoning. A survey of the literature describes many studies which demonstrate that acrylonitrile and propionitrile are converted in vivo to toxicologically significant concentrations of cyanide and that sodium thiosulfate, an established cyanide antagonist, can provide protective actions against poisoning by either acrylonitrile or propionitrile. The observations suggest that the teratogenic effects of both acrylonitrile and propionitrile are related to the metabolic release of cyanide. PMID- 6266065 TI - Genetic aspects of the effects of methylmercury in mice: the incidence of cleft palate and concentrations of adenosine 3':5' cyclic monophosphate in tongue and palatal shelf. AB - Concentrations of adenosine 3':5' cyclic monophosphate (cAMP) were measured in the tongues and palates of 14.5-day-old fetuses from control and methylmercury treated mothers of four inbred lines of mice which represent the four possible combinations of two H-2 alleles and two residual genetic backgrounds. The incidence of cleft palate in fetuses from control and methylmercury-treated mothers was also examined. The H-2 alleles significantly affected the degree of reduction of cAMP concentration in palates seen in fetuses from mothers treated with methylmercury. Neither the H-2 allele nor the residual genetic background played a role in the effect of methylmercury on cAMP concentrations in fetal tongues. The magnitude of increase in the incidence of cleft palate with methylmercury treatment was approximately the same for all lines. Thus, methylmercury-induced cleft palate may not be mediated by the reduction of cAMP. Finally, fetuses with cleft lip had increased palatal cAMP levels, whether or not they were from control or methylmercury treated mothers. PMID- 6266066 TI - Effects of any epoxymethano stable analogue of prostaglandin endoperoxides (U 46619) on human platelets. AB - U-46619 is a stable epoxymethano analogue of cyclic endoperoxide PGH2. We studied platelet aggregation, 14C-5HT release, LDH extrusion and prostaglandin and thromboxane production induced by this compound in platelet-rich plasma samples from 15 healthy volunteers. Each subject was tested both before and 90 min after aspirin (500 mg) ingestion. The threshold aggregating concentration (TAC) of U 44619 ranged between 0.18 and 0.90 micro M. Aggregation was maximal between 40 and 60 min after venipuncture and was concentration-dependent. At concentrations below the TAC, U-44619 induced primary reversible aggregation with minimal 14C 5HT release. At TAC or higher concentrations aggregation and release proceeded as parallel events. Neither prostaglandin or thromboxane production nor LDH loss could be detected in any of the situations tested. Aspirin ingestion did not modify the pattern of platelet responses. In unstirred, not aggregated platelet samples 14C-5HT release by U-46619 occurred to a similar extent as in stirred, aggregated platelet samples. Addition to citrated PRP of 0.3 mM Na2 EDTA blocked both aggregation and release induced by U-46619. This compound, however, aggregated washed platelets resuspended in Ca++-free-tyrode-albumin containing fibrinogen. The mechanism by which U-46619 activates platelets differs from that of all other common aggregating agents. PMID- 6266067 TI - Modification of platelet function by radical species produced during irradiation of oxygenated water. AB - Gel-filtered platelets in neutral, oxygen-containing solutions irradiated to a dose of 10 krad with gamma-rays display a significant inhibition of ADP-induced aggregation. Though the superoxide anion radical (O2-.) and H2O2 are generated in water irradiated under these conditions, only catalase, but not superoxide dismutase (SOD), conveyed protection against this inhibition of platelet function. When the platelets are in the presence of 10(-3) M sodium formate, which converts the majority of the radical species formed to O2-., inhibition of aggregation was again observed. Under these circumstances, the addition of catalase significantly decreased this inhibition, whereas the addition of SOD was without effect. In order to separate the platelet-inhibition effects of the radical species generated in the medium from a direct effect of irradiation on platelet components, relatively stable quantities of O2-. were produced in alkaline solutions and reacted with gel-filtered platelets. Again, an inhibition of ADP-induced aggregation was observed. This inhibition was not significantly altered by the addition of SOD, but was abolished by the addition of catalase, either with or without SOD. Our observation would indicate that O2-. is without direct effect on platelet function, but serves as the precursor of H2O2, which can inhibit platelet reactions. PMID- 6266068 TI - Lithium inhibits adenylate cyclase of human platelets. AB - The ADP-induced aggregation of human platelets is markedly increased after preincubation with lithium chloride, whereas lithium has the opposite effect on rabbit platelets. Since this phenomenon might be related to cAMP metabolism, the influence of lithium on total cAMP content and adenylate cyclase activity was investigated. Lithium does not significantly change the total cAMP content of human platelets neither during incubation nor during ADP-induced aggregation. Basal adenylate cyclase activity, however, was slightly inhibited by lithium in human platelets. The inhibition of adenylate cyclase by ADP appeared to be enhanced by lithium. Prostacyclin induced stimulation of adenylate cyclase is counteracted by this ion. In rabbit platelets the prostacyclin stimulated adenylate cyclase activity is not affected by lithium. These data suggest that a correlation exists between the influence of lithium on the aggregation of human and rabbit platelets and the sensitivity of their adenylate cyclase for this ion. PMID- 6266069 TI - Human spleen insoluble fibrinolytic proteinase acting at neutral pH: its partial purification and characterization. AB - An insoluble fibrinolytic enzyme with a molecular weight of approximately 30,000, was purified from the human spleen. A single protein band possessing fibrinolytic activity was obtained on polyacrylamide gel disk electrophoresis at pH 4.5. The enzyme, tentatively termed spleen fibrinolytic proteinase (SFP), degraded fibrinogen at neutral pH following Michaelis-Menten kinetics. The fibrinogenolytic activity was not inhibited by t-AMCHA, a specific plasmin inhibitor. SFP barely degraded certain synthetic ester or polypeptide substrates for trypsin, chymotrypsin, plasma, Xa, elastase and collagenase. These results indicate a different nature for SFP compared to other enzymes examined. SFP was found to digest no elastin and its fibrinogenolytic activity was strongly inhibited by STI, indicating that it was not an elastase. SFP required neither Zn++ nor CA++ for its fibrinogenolytic activity, indicating that it differed from metal-dependent proteinases such as collagenase. SFP was inhibited by DFP but not by TLCK, suggesting that it contains an active serine residue, but no trypsin type histidine at its active center. These results appear to show that SFP is a unique proteinase in the spleen, which is capable of degrading fibrin and fibrinogen at neutral pH. PMID- 6266070 TI - Immunoglobulin production in Epstein-Barr virus-induced human monoclonal lymphoblastoid cell lines. AB - In order to establish clonal human lymphoblastoid cell lines, human tonsillar lymphocytes infected with Epstein-Barr virus were directly seeded in semi-solid agar. After four weeks, resulting colonies were randomly isolated and transferred to suspension culture. At around three months after the initiation of the culture, immunoglobulin (Ig) production of 17 clones thus established was determined. Cytoplasmic and membrane Ig were detected by immunofluorescence staining and secretory Ig in the culture supernatants was detected by double immunodiffusion. The patterns of Ig production by these cell lines were clear cut. Each clone produced and secreted one class of heavy chains and one type of light chains, i.e., a single Ig. Of 17 clones, 13 clones were IgM producers, 3 clones were IgA producers and one clone was an IgG producer. Membrane Ig of these clones was also identical with cytoplasmic/secretory Ig with the exceptions of three IgM producers in which membrane IgD as well as IgM was detected and the one IgG producer in which no membrane Ig was detected. PMID- 6266071 TI - The important role of graft organization at the vascular prosthetic anastomosis. AB - The vascular anastomosis free of suture was made by using an absorbable suture and its tensile strength was compared with that of non-absorbable suture anastomosis. 29 adult mongrel dogs weighing 7.5 to 13.5 kg were used. Two kinds of vascular anastomosis were performed, that is, artery-to-artery anastomosis and vascular prosthetic graft to artery anastomosis. They were made in the right carotid artery and the abdominal aorta, respectively. Two kinds of suture were used for the vascular anastomosis, i.e., polyglycolic acid suture as an absorbable suture and TEVDEK suture as a non-absorbable suture. The tensile strength of anastomosis was measured by a self-made tensiometer. The following results were obtained: In the artery-to-artery anastomosis, the loss of the strength of suture did not weaken the anastomosis, whereas in the vascular prosthetic anastomosis, the loss of the tensile strength of suture weakened the vascular prosthetic anastomosis. However, well organized fibrous tissues surrounding the vascular prosthesis were strong enough to hold against the blood pressure. PMID- 6266072 TI - Cyclic AMP concentrations in plasma, cerebrospinal fluid and urine in patients with acute cerebral hemispheric infarction. AB - Plasmas, cerebrospinal fluid and urine were sampled from 22 patients with cerebral hemispheric infarction and analyzed for cyclic AMP. The following observations were made: (1) In mild cases with slight dysarthria and/or hemiparesis but without disturbance of consciousness (Group I), cyclic AMP in peripheral venous plasma (PVP) remained over the normal lowest level more than 10 days after the onset. Patients with apparent neurological deficits could be divided into two groups. In one group, cyclic AMP in PVP decreased to a subnormal level within about 5 days after the onset of stroke (Group II). In another group (Group III), such a decrease was not observed. Brain isotope scintigrams were revealed negative in Group I. The size of brain infarct as judged by isotope uptake was larger in Group III than in Group II, except for a few cases in which the lesion was restricted in the basal ganglionic region. (2) No clinical significance was, however, found in the time course of cyclic AMP levels in internal jugular venous or femoral arterial plasma, or in cerebrospinal fluid, or of the daily amount of cyclic AMP excretion into urine. (3) Cerebral arterio venous difference of cyclic AMP was negative in most of the cases. PMID- 6266073 TI - Histochemical and ultracytochemical detection of pyridoxal and pyridoxamine phosphate hydrolase in rat tissues. PMID- 6266074 TI - Influence of dietary polybrominated biphenyl on antibody and host defense responses in mice. PMID- 6266075 TI - A possible mechanism for changes in renal K+-dependent phosphatase activity in lead-treated rats. PMID- 6266076 TI - Inhibition of sterologenesis but not glycolysis in 2,5-hexanedione-induced distal axonopathy in the rat. PMID- 6266077 TI - Altered lipid metabolism in 2,5-hexanedione-induced testicular atrophy and peripheral neuropathy in the rat. PMID- 6266079 TI - Lead poisoning in monkeys: functional and histopathological alterations of the kidneys. AB - Ten monkeys (Macacus Irus) were given 0--15 mg of lead acetate (in drinking water) 6 days a week for 9 months. Two of the monkeys were also put on a low calcium diet with 6 mg of lead acetate/day. The blood lead level usually increased from the third month according to the dose of lead ingested and more quickly in monkeys deprived of calcium. Some of the monkeys showed signs of alteration in protein glomerular filtration and/or proximal tubular reabsorption. Studies using optical and electron microscopy showed distinct pathological changes in the proximal tubular epithelium where heavy deposits of lead were seen in the nuclei. PMID- 6266078 TI - Biochemical and physiological sequelae to perinatal exposure to polybrominated biphenyls: a multigeneration study in rats. PMID- 6266080 TI - Effects of the herbicide 2, 4-dichlorophenyl-p-nitrophenyl ether (nitrofen) on fetal lung development in rats. PMID- 6266081 TI - Comparative induction of xenobiotic metabolism in rodent kidney, testis and liver by commercial mixtures of polybrominated biphenyls and polychlorinated biphenyls, phenobarbital and 3-methylcholanthrene: absolute and temporal effects. AB - Male Fischer 344 rats were killed at various times after single or multiple treatments with polybrominated biphenyls (PBB), polychlorinated biphenyls (PCB), sodium phenobarbital (NaPB) or 3-methylcholanthrene (3MC). p-Chloro-N-methyl aniline N-demethylase (PCNMA) and aryl hydrocarbon hydroxylase (AHH) activities were determined in the 14 000 g supernatant fraction (postmitochondrial supernate, PMS) of renal, testicular and hepatic homogenates. Cytochrome P-450 (p 450) concentrations were determined in the 100 000 g pellet fractions of the same homogenates and the effects of enzyme induction on the sensitivities of AHH in PMS to inhibition by alpha-napthoflavone (ANF) and metyrapone (MET) in vitro were determined. Single treatments with PBB or PCB induced hepatic P-450 only, while multiple treatments with PBB, PCB or 3MC induced both renal and hepatic P-450; NaPB induced only hepatic P-450, while testicular P-450 concentration was unaffected by the inducers. Treatments with PBB, PCB or 3MC shifted the Soret maxima of renal and hepatic dithionite-reduced P-450 difference spectra to shorter wavelengths. Multiple treatments with PBB, PCB or 3MC increased renal and hepatic AHH activities, but NaPB induced hepatic AHH only. Renal AHH activity was increased more rapidly than hepatic AHH after a single treatment with PBB, PCB or 3MC and returned more rapidly to control. The renal AHH induced by PBB and PCB, like that induced by 3MC, was more sensitive to inhibition by ANF in vitro than was renal AHH from naive rats. Hepatic AHH induced by PBB and PCB, unlike that induced by NaPB or 3MC, exhibited no net alterations in sensitivities to the inhibitory effects of ANF or MET. Testicular AHH activity was not induced by PBB, PCB , NaPB or 3MC. Multiple treatments with PBB, PCB or NaPB increased hepatic, but not renal or testicular PCNMA activities. The organ-specificity and time dependency of the effects of PBB, PCB, NaPB and 3MC on P-450 concentrations and AHH activities suggest that drug metabolism in kidney, testis and liver are regulated by separate control mechanisms. It may be possible to exploit such differences in organ response to enzyme inducers as tools with which to discern the roles of local metabolism in renal and testicular chemical injury. PMID- 6266083 TI - Management of lymphatic leakage after renal transplantation. PMID- 6266082 TI - A sensitive competitive protein binding assay for vitamin D in plasma. AB - A sensitive protein binding assay for vitamin D is described. The vitamin D3 was extracted from plasma with diethyl ether and methylene chloride. The lipid extract was purified in Sephadex LH-20 followed by Lipidex 5000 and finally by high pressure liquid chromatography on a Zorbax Sil column (0.79 x 25 cm) developed in 0.25:99.75 isopropanol: methylene chloride. The vitamin D fraction was collected and quantitated by competitive protein binding assay with a 1/50,000 dilution of sheep plasma in 0.05 M potassium phosphate buffer (pH 7.5) containing 0.01% gelatin. [H3]-25-Hydroxyvitamin D3 was used as a radioactive tracer in the assay. We found that under these conditions, sheep plasma had equal affinity for vitamin D2 and vitamin D3 and could detect as little as 0.1 ng of vitamin D. When rat, cow, or human plasma was substituted for the sheep plasma, the decline in sensitivity to vitamin D2 was fivefold to tenfold. With this assay, we found excellent agreement (r = 0.98) between the results obtained by competitive protein binding analysis and direct U.V. absorbance analysis by high pressure liquid chromatography. PMID- 6266084 TI - Effects of antithymocyte globulin on cytomegalovirus infection in renal transplant recipients. PMID- 6266085 TI - Effect of silica pretreatment and cyclosporin A therapy on isolated islet allografts in the rat. PMID- 6266086 TI - [Comparison of the transforming DNA of Bac. subtilis and Bac. natto for sensitivity to EcoR1 restrictase]. AB - Transformation procedures were used to study the residual activity of various genetic markers belonging to both Bac. subtilis and Bac. natto after treating their DNAs with EcoRI endonuclease. It is shown that in case of Bac. natto DNA the residual transforming activity of ade, thy and rib markers is 5,10 times higher in comparison with Bac. subtilis DNA. Bac. natto is suggested to be used as a source of genes in gene engineering. PMID- 6266088 TI - [Ultrastructural and cellular functional activity changes in the zona fasciculata of the rat adrenal cortex resulting form the prolonged administration of adrenocorticotropic hormone]. AB - The fasciculata zone cell ultrastructure has been studied in addition to the level of steroidogenesis of rat adrenal glands on days 2,7 and 13 after the administration of ACTH with prolonged action. The marked changes in the ultrastructure of different cells have been noticed, some of which suggest a compensatory stimulation of hormone production, and the others indicate irreversible subcellular injuries. Changes in the cell ultrastructure show the phase character in time to correlate with changes in the activity of the corticosteroid synthesis and secretion. PMID- 6266087 TI - [Increase in the cAMP content of mouse brain cells in ischemia and inhibition of this effect by certain biologically active compounds]. AB - Anoxia (during 2 minutes after decapitation) produced a significant elevation of cAMP contents (up to 410%) in mouse brain cells. This effect was abolished by an intraperitoneal injection of alloxan (A), morphine (M), and ethanol (E) 30 minutes before decapitation, and after a 2 minutes diethyl ether (DE) inhalation. It was found that anoxia produced some decrease in phosphodiesterase (FDE) activity. A preliminary injection of A and E produced an activation of FDE; M and DE did not change FDE significantly. Mechanisms of action of all the four agents on the cAMP content under anoxia are different. A and E produced a rapid cAMP hydrolysis on stimulating the activity of FDE, M and DE inhibited apparently adenylate cyclase. The activation of adenylate cyclase due to anoxia is considered as one of the initial steps in the cell injury extention. PMID- 6266089 TI - [Age sensitivity characteristics of the human and mouse chromosome apparatus in exposure to viral infection]. AB - It is determined that the measles virus (vaccine strain Leningrad-16) induce cytogenetic alterations in bone marrow cells in all the examined mice, the most considerable aberrations being noted in newly born and especially aged mice. Coxsackie virus A13 is capable of causing cytogenetic aberrations in newly born and aged mice, while the puberal mice of the middle aged group are resistant to the mutagenic effect of the virus. Flu patients aged 65-80 and 2-5 years suffer from the biggest alterations in the blood chromosome leucocytes, with the decrease in number and in T-lymphocyte functional activity. The patients aged 18 35 years suffered less. PMID- 6266090 TI - [Changes in the nucleoside phosphatase activity and the ultrastructural organization of ribonucleoproteins in rat hepatocyte nuclei as affected by actinomycin D]. PMID- 6266092 TI - Evidence of sheep pox in Nigeria. PMID- 6266091 TI - Antigenic types of bluetongue virus prevalent in Egypt. AB - In an attempt to identify the antigenic types of bluetongue (BT) virus prevalent in Egypt 31 selected sheep sera from different parts of Egypt which had been screened by gel precipitation tests were examined by a plaque reduction test using 16 types of BT virus. Dilutions 1:5 of those screened sera reduced more than 50% of plaques of at least 1 of 16 types of BT virus. Two sera completely inhibited plaque formation with type 4 virus, 1 with type 13, another serum with type 15 and 2 other ser with type 16 virus. The significance of the above serological findings is discussed. PMID- 6266093 TI - [Primary tumors of the mediastinum: apropos 37 cases]. PMID- 6266094 TI - [Potassium release from erythrocytes of different age rats in 9 simulated lactic acidosis]. AB - The methods are described for determination of potassium content in erythrocytes by means of a K+ selective electrode, for evaluation of changes in potassium permeability through their membranes and for detection of the Na+, K+-ATPase contribution to spontaneous and induced cation release from cells. Preincubation of erythrocytes with 5 mM lactate has no effect on the potassium release rate and content in cells of young and adult rats. Under the effect of 25 mM lactate the rate of K+ release from erythrocytes of adult animals lowers and sensitivity to ouabaine of this process stimulated by valinomycin increases. The latter effect is less pronounced in erythrocytes of young rats and is accompanied by a rise in potassium total content in cells. PMID- 6266095 TI - [[14C] Alanine incorporation into proteins and their contents in the tissue of intact and adrenalectomized rabbits after hydrocortisone and cortitropin administration]. AB - A single administration of hydrocortisone to intact rabbits increases the incorporation of [14C] alanine into proteins of the brain and liver tissue homogenates and soluble fractions as well as in blood plasma proteins and reduces the label incorporation into the brain tissue proteins and reduces its incorporation into the blood plasma proteins. Adrenalcetomy is followed by an increase in the incorporation of [14C] alanine into proteins of the brain and muscle tissue homogenates and soluble fraction and into proteins of blood plasma and liver tissue homogenates as well as by reducing the label incorporation into the spleen soluble fraction proteins. ACTH administered to adrenalectomized rabbits reduces incorporation of [14C] alanine into the brain and muscle tissue proteins, total proteins of liver tissue homogenate and increases it into the proteins of the spleen tissue soluble fraction. Multiple administration of the soluble fraction hormones both to intact and adrenalectomized rabbits inhibits the label incorporation into the studied tissue proteins. Parallel with the change in [14C] alanine incorporation into proteins under the hormones effect certain shifts in their contents were also established. PMID- 6266096 TI - [Effect of training and physical load on 3':5'-AMP content and activity fo the enzymes of its metabolism in rat muscle]. AB - It is established tha in skeletal muscles of dormant animals under the influence of training the 3':5'-AMP content and the activity of adenylate cyclase increase; that of phosphodiesterase remains unchanged. A long physical load causes no changes in the 3':5"-AMP content in the skeletal muscles of the trained rats as compared to its content in the intact animals but evokes a decrease as compared to its level in the trained rats muscles. The activity of adenylate cyclase in the skeletal muscles of the trained rats under long physical load lowers, that of 3':5'-AMP phosphodiesterase also decreases but to a less extent. The found changes in the 3':5'-AMP metabolism in the trained animals skeletal muscles evidence for a possible participation of the 3':5'-AMP system in development of the organism adaptation to higher physical loads. PMID- 6266097 TI - [Immobilization of Penicillium vitale Pidopl. et Bilai catalase by inorganic carriers]. AB - An efficient method is developed for P. vitale catalase immobilization through the oxidized carbohydrate enzyme component, using silochrome. The method provides the enzyme binding without losing its catalytic capacity in the immobilized preparation. When the enzyme is immobilized by high-dispersed silica containing isocyanate, aldehyde groups or active atoms of chlorine, 8, 15, and 20 mg of the enzyme is bounded per 1 g of the carrier, respectively, its catalytic capacity being completely retained. A dependence is established for the degree of catalase bonding and catalytic capacity of the immobilized enzyme of the enzyme carrier ratio in immobilization. The catalytic activity of the immobilized catalase preparations reaches 2 000 Becker units/l g. The preparations are stable in storage. Some of their properties are studied. PMID- 6266098 TI - [Dependence of calcium absorption in the chicken small intestine on its Ca2+ binding protein content and the effect of exogenous nucleotide precursors on this process]. AB - A dependence was studied between the level of calcium absorption and the content of calcium-binding protein in the small intestine of D-hypovitaminous chickens to whom different exogenic precursors of nucleotides (potassium orotate or guanine) were administered at different stages of the response (0-72 h) to a single administration of vitamin D3 in a dose of 500 MU. It is established that under the effect of potassium orotate or guanine the degree of discrepancy between calcium adsorption and the content of Ca2+-binding protein increases at all stages under investigation. The results of the mathematical analysis of the experimental data which is based on the supposition of the linear dependence between the level of absorbed calcium and Ca2+-binding protein evidence for a considerable rise in the excess amount of the latter, which possibly does not take part in cation absorption, in the chickens who were administered nucleotide exogenic precursors. The data obtained show that the amount of calcium-binding protein is not a limiting factor in the mechanism of vitamin D3 stimulation of calcium absorption in the chicken small intestine. PMID- 6266099 TI - [Effect of ethylenediamine derivatives on Na+, K+-ATPase and K+-p-nitrophenyl phosphatase activity of brain enzyme preparations]. AB - The activity of Na+, K+-ATPase preparations was studied as affected by ethonium and its analogs. Ethonium is found to be able of producing a strong inhibitory effect on the Na+, K+-ATPase and K+-n-nitrophenyl phospnatase activities (I50 = 2.5.10(-5) and 6.5.10(-5) M, respectively). The inhibition is irreversible under experimental conditions and is reduced when the concentration of protein and sodium ions in the incubation medium rises. A dependence is found between the inhibitory effect of the analogs and the length of their hydrocarbon radical (the inhibition maximum corresponds to bisquarternary ammonium compound with the hydrocarbon radical consisting of 10 links) and some kinetic characteristics of this effect are studied. It is supposed that the mechanism of the inhibitory effect is due to the ethonim binding by the hydrocarbon radical in the preparation hydrophobic zone, the electrostatic interaction being not excluded. PMID- 6266100 TI - [Rapid method for the determination of choline kinase activity. Choline kinase in marine invertebrates]. AB - A quick sensitive test is suggested to determine choline kinase (EC 2.7.1.32). The method includes incubation of a substrate with enzyme in microvolume and separation of the formed phosphorylcholine from the initial choline by high performance thin-layer silica gel chromatography. The procedure of determination is simple, reproducible and takes no more than 30 min. The method reveals high activity of choline kinase in some marine invertebrates. Certain features of the enzyme from the intestine of strongylocentrotus intermedius are described. PMID- 6266101 TI - [Adenylate cyclase system and structural modifications of nuclear proteins in organisms radioprotection]. AB - The paper deals with modern ideas of ways and mechanisms for realization of the radioprotector antiradiation effect. The data on the effect of biogenic amines (serotonin in particular) and radiation on the cAMP system are analyzed. It is shown that one of the most important mechanisms of the radioprotective effect is realized by changing the levels of histones and nonhistone proteins modifications through the adenylate cyclase system which leads to regulation of the chromatin template activity. PMID- 6266102 TI - [Phosphodiesterase of cyclic nucleotides]. AB - Problems are considered on form multiplicity, purification and molecular weight of cyclic nucleotides phosphodiesterase. A supposition is made that the molecular weight of the catalytic subunit of the enzyme for most studied objects is about 60000. The catalytic subunit may form di- and trimers and be associated with regulatory proteins of different type. The problem of phosphodiesterase regulation is analyzed on the basis of potentialities of the equilibrium shift between the protein subunits of the enzyme; the role of cyclic nucleotides as well as of triphosphonucleotides are shown to influence the regulation of the enzymic activity. In some cases the mechanism of changes in the activity of phosphodiesterase bound with the receptor is shown to be similar to that for adenylate cyclase. In particular, the role of GTP and one of the protein subunits of phosphodiesterase in this process is stated. PMID- 6266103 TI - [Role of biological membrane lipid component in hormone reception and adenylate cyclase system function]. AB - The paper deals with a review of experimental data evidencing for an important role of phospholipids in regulation of the activity of the adenylate cyclase system sensitive to hormonal effects. These compounds play a structural role and evidently keep the receptor-enzymic complex in the state sensitive to the hormone effect. Phospholipids form a complex with the receptor subunit of adenylate cyclase or determine its microenvironment and take part in hormonal binding. Lipid components are transmitters or modulators of physico-chemical signals formed during hormone-receptor interaction. A supposition is made that phosphatidyl ethanolamine, phosphatidyl serine and probably phosphatidyl inositol interact with the catalytic subunit of adenylate cyclase and determine its activity. Supposing that several hormonal receptors are associated with adenylate cyclase only, it may be admitted that each receptor is linked with it through separate fractions of phospholipids. PMID- 6266104 TI - [Participation of adenylate cyclase in conducting hormonal signals through membranes]. AB - Mechanisms are considered which conduct and amplify a hormonal signal with participation of adenylate cyclase. It is shown that cell sensitivity to hormone is governed by the constant of receptor affinity for hormone, by the content of receptors in the membrane as well as of the degree of receptors conjugation with the enzyme. Mechanisms regulating the amount of receptors in the membrane, the role of guanylic and other purine nucleotides in their functioning are discussed. Properties of GTR-dependent proteins realizing the functional conjugation of receptors with adenylate cyclase and models of adenylate cyclase complex molecular organization and functioning in the membrane are discussed. The complex of catalytic subunit with GTP-dependent protein is a choloenzyme of adenylate cyclase. An assumption is made that not only GTP but also GDP may influence the formation of this complex. The adenylate cyclase activity is regulated by variations in the equilibrium between apo- and choloenzyme, different agents changing this equilibrium, affecting either protein-protein of protein-nucleotide interaction. The presence of several GTP-dependent centres is supposed to be in the adenylate cyclase complex, in one of which GDP may be transformed to GTP due to the phosphotranspherase reaction. PMID- 6266105 TI - [Cyclic nucleotides in the regulation system of cell proliferation and differentiation]. AB - The paper deals with certain aspects in the role of cyclic nucleotides in cell differentiation and proliferation. The content of cyclic nucleotides and activity of protein kinases are determined for the cell cycle stages of a synchronous plasmodium culture of true myxomycete Physarum polycephalum. Studies in the biological role of the brain cAMP-dependent protein kinase show that during phosphorylation of nuclei from the brain and subsequent isolation of chromatin its matrix activity is higher than the control one. When a regulatory subunit is added to the standard RNA-polymerase reaction, the total level of transcription increases for eucaryote RNA-polymerase. The constant of the regulatory subunit binding with chromatin from the brain is 10(10) M-1. Studies in translocation of tritium-labelled cAMP-dependent protein kinase and its subunits to interphase nuclei and in acception of these proteins by metaphase chromosomes in different cell cultures state that sAMP-dependent protein kinase penetrates into the nucleus in the dissociated state. It is established that disturbance of the regulatory subunits translocation into the nucleus and its acception by chromosomes when cell are transformed by SV40 virus is completely restored by adding cAMP. For cells, which suffered the malignant transformation of another type (spontaneous human cancer--KB, HeLa), and essential nuclear translocation and a complete absence of acception by chromosomes for the regulatory subunit are found. An assumption is made that compartmentation of cAMP-dependent protein kinase, in particular of its regulatory subunit, plays an important role in the organism vital activity and disturbances arising in neoplastic transformation are connected with changes in translocation and acception of the regulatory subunit in the nucleus. PMID- 6266107 TI - [Significance of studies on cyclic nucleotide metabolism for practical medicine]. AB - Based on the results of own studies and data available in literature the evidence is given on peculiarities of determination and estimation criteria for the content of cyclic nucleotides in people. Changes in the metabolism of these substances and their pathogenic role are considered for a large number of diseases. Pharmacotherapeutic aspects are described, in particular regulation of enzymes taking part in the metabolism of cyclic nucleotides. The data are presented pertaining to the clinical application of phosphodiesterase inhibitors in oncology, in diseases of the cardiovascular system, respiratory system and in neuropathology. Approaches to a selective modification of cyclic nucleotides metabolism in clinical practice are considered. PMID- 6266106 TI - [Participation of cyclic nucleotides in immunogenesis and immune reactions of lymphocytes]. AB - The paper deals with generalized literary and author's own data testifying to the role of cyclic nucleotides as mediators in the effect of specific and nonspecific factors on immunogenesis, from the proliferation of stem hemopoietic cell of bone marrow to the reaction of T and B lymphocytes to antigens. It is shown that changes in the system of lymphocytes cyclic nucleotides are most probably secondary in response to changes in intracellular concentration and distribution of calcium ions. Certain evidence is presented on immunopharmacological preparations based on cyclic nucleotides, their analogs and preparations modulating the activity of phosphodiesterases. PMID- 6266108 TI - [Changes in the activity of cyclic nucleotide phosphodiesterase and content of rhodopsin in retina during long illumination]. AB - The phosphodiesterase activity in rat retina is found to decrease after a relatively short (1 h) and long (24 and 48 h) light exposition at 1200-1700 lx. illumination. The degree of decrease in the enzymic activity correlates with the exposure time. The rhodopsin capacity for regeneration is a criterion of the activity changes in the retina under the light effect. An hour illumination after the dark adaptation restores practically the initial level of the rhodopsin content and phosphodiesterase activity. A one- and two-day stay in the light causes a partial disturbance in the regeneration of rhodopsin and essential disturbances of the phosphodiesterase activity recovery in the retina. PMID- 6266109 TI - [Changes in Na+, K+-ATPase and acetylcholinesterase activity in red cell membranes after freezing-thawing]. AB - The activity of Na+, K+ATPase (EC 3.6.1.3) and acetylcholinesterase (EC 3.1.1.7) as well as the content of masked and exposed SH-groups in sealed and unsealed erythrocyte ghosts were studied as affected by single rapid freezing-thawing. The freezing-thawing procedure resulted in different reactions of membrane-bound enzymes: Na+, K+-ATPase activity is doubled in sealed ghosts and unchanged in unsealed ones. In both types of ghosts the equal decrease in the AChE activity was found to be parallel with the diminution in the content of masked SH-groups but this cannot be referred to exposed SH-groups. The obtained results seem to suggest that the changes in the native conformation of membrane catalytic proteins resulted from cryodamage are responsible for the lowered aChE activity; the primary cause of increase Na+, K+-ATPase activity is due to the changes in the permeability and integrity of erythrocyte membrane, which are followed by the greater accessibility of the substrate (ATP) to the enzyme. PMID- 6266110 TI - [Effect of thiamine deficiency and excess on activity of NA+, K+, Mg2+-ATPase in plasma membranes of rat liver]. AB - The activity of Na+, K+, Mg2+-ATPase in plasma membranes of the rat liver was studied as affected by thiamine, oxythiamine and food B1-avitaminosis. It is shown that the ATPase activity of the liver plasma membranes is inhibited only in case of modelling the alimentary thiamine deficiency. PMID- 6266111 TI - [Activation of brain K+-phosphatase and Mg2+, Na+, K+-AtPase by sodium alkyl sulfates]. AB - K+-dependent phosphatase and Mg2+, Na+, K+-ATPase were studied under the activating effect of surfactant homologs of the alkyl sulphate series with the hydrocarbon radical long chain C4-C15. The homologs are shown to activate the enzymes when they are in the molecular-disperse but not in micellar state. A clear regularity is observed in the effect of these surfactants on K+-phosphatase depending on the length of the hydrocarbon radical chain: the degree of the activating effect rises with the chain lengthening, reaching the maximum value when the number of carbon atoms is 12. The lower and upper bounds of the alkyl sulphate hydrocarbon radical chain length necessary for manifestation of the activating effect shift somewhat for K+-dependent phosphatase as compared with Mg2+, Na+, K+-ATPase. The data obtained evidence for a stronger stability of the phosphatase to a destructive effect of the surfactants as compared with transport ATPase. PMID- 6266112 TI - [Detection of a stromal luteoma of the ovary using 131I-iodocholesterol scintigraphy]. PMID- 6266114 TI - Tendon-lengthening operations for squint. PMID- 6266115 TI - [The effect of vaccination on the intrauterine transmission of Aujeszky's disease virus in sows]. AB - Eight of ten sows of the Large White breed were vaccinated in different stages of pregnancy, with an inactivated vaccine against Aujeszky's disease. The other two sows remained untreated. Two virulent strains of the Aujeszky's disease virus were used for the infection of all sows, either orally or intravenously. Neither of the two ways of infection led to the transmission of the virus to the foetus in any of the eight vaccinated sows. On the other hand, in the two unvaccinated sows, the virus was transmitted to the foetus only after intravenous infection, whereas oral infection did not lead to the transmission of the virus to the foetus. PMID- 6266116 TI - Canine hepatocellular carcinoma. AB - In a study of 110 primary hepatic neoplasms in dogs, 55 hepatocellular carcinomas and two combined hepatocellular and cholangiocarcinomas were diagnosed. These neoplasms were classified into the following 11 groups based on histo architectural pattern: trabecular, peliod, cobblestone, peritheliomatous, anaplastic, pseudoglandular, pleomorphic, scirrhous, clear cell, solid, and combined hepatocellular and cholangiocarcinoma. The neoplastic hepatocytes varied from almost normal to highly anaplastic spindle cells. Pleomorphic and giant cells were common in some groups, rare or absent in others. Metastasis was found in 61% (35 of 57), in contrast to a much higher percent in man, indicating the possibility of a different pathogenesis in the dog. PMID- 6266118 TI - Classification of lung carcinomas in the dog and cat. AB - A total of 218 lung carcinomas from dogs and cats were examined histologically. The tumors were classified into adenocarcinoma, squamous-cell carcinoma, bronchial gland carcinoma, and alveolar-cell carcinoma. We believe that adenocarcinoma should be subdivided into differentiated and undifferentiated types because the two are distinct histologically and vary in frequency in the cat and dog. It is also important to recognize bronchial gland carcinoma, a distinct histological type, and to subdivide alveolar-cell carcinoma into three separate types: anaplastic small-cell and large-cell types, and adenomatosis type. PMID- 6266113 TI - Chemotherapy of experimental endogenous Candida albicans endophthalmitis. PMID- 6266117 TI - Canine bile duct carcinoma. AB - Twenty-four adenocarcinomas of the hepatobiliary system were found among 110 primary hepatic neoplasms: 22 of these were intrahepatic, one involved the extrahepatic bile duct and one the gall bladder. Histologically, 10 intrahepatic neoplasms were classified as cholangiocarcinoma, and 12 as bile duct cystadenocarcinoma. The former were characterized by tubular structures lined by anaplastic cuboidal or columnar cells with diffuse fibrous stroma, and the latter by multiple cystic structures with papillary and solid areas. Half the bile duct cystadenocarcinomas showed benign cysts and transition to adenocarcinomas. This was seen in only one case of cholangiocarcinoma. The extrahepatic bile duct carcinoma was characterized by tubular structures lined with flattened cuboidal cells with scant stroma. The gall bladder adenocarcinoma contained many acinar structures lined with columnar or cuboidal cells and separated by thin stroma. Distant metastasis was found in 87.5% (21 of 24) sites of metastasis. PMID- 6266119 TI - Antigenic differences between canine parvovirus and feline panleucopenia virus. PMID- 6266121 TI - Disease outbreak in calves caused by a mixed infection with infectious bovine rhinotracheitis virus and bovine virus diarrhoea virus. PMID- 6266120 TI - Isolation of bovine virus diarrhoea virus from a Scottish red deer. PMID- 6266122 TI - The aetiology and diagnosis of calf diarrhoea. PMID- 6266124 TI - Bovine abortion associated with infectious bovine rhinotracheitis virus infection. PMID- 6266123 TI - Immune responses of breeding chickens to trivalent oil emulsion vaccines: responses to Newcastle disease and infectious bursal disease. AB - Bivalent Newcastle disease (ND)/infectious bursal disease (IBD) and trivalent ND/IBD/infectious bronchitis (IB) inactivated oil emulsion vaccines were prepared in the laboratory and evaluated under field conditions. Broiler breeder parent chickens previously vaccinated with live vaccines were inoculated with commercial monovalent ND and experimental bivalent or trivalent oil emulsion vaccines. The commercial vaccine induced a higher initial ND haemagglutination inhibition (HI) response than the experimental vaccines but, by 34 weeks after vaccination, the mean ND HI levels were not significantly different in any of the three flocks. All three vaccines provided sufficient ND immunity to protect against the clinical disease and egg production losses. The IBD responses of both flocks vaccinated with oil emulsion vaccine were similar to each other and only slightly lower than those flocks vaccinated with monovalent IBD oil emulsion vaccine in earlier experiments. Six weeks after vaccination, sufficient immunity was transferred to protect all the progeny against IBD challenge up to 33 days of age and some of them up to 45 days of age. Thirty-four weeks after vaccination of the parents with oil emulsion vaccine, the progeny were totally immune up to 27 days of age and some of them were immune until 37 days. Application of oil emulsion vaccines in bivalent or trivalent form did not impair the responses of the chickens to the monovalent components. PMID- 6266125 TI - Immune responses of breeding chickens to trivalent oil emulsion vaccines: responses to infectious bronchitis. AB - Three similar flocks of broiler breeder parent chickens that had been given live infections bronchitis (IB) vaccines during rearing were injected at 20 weeks of age with three different oil emulsion vaccines: a commercial monovalent Newcastle disease (ND) vaccine (flock A); an experimental bivalent vaccine containing ND and infectious bursal disease (IBD) components (flock B); and an experimental trivalent vaccine containing ND, IBD and IB components (flock C). One week after vaccination 40 hens from flock A and 40 from flock C were taken to the laboratory and their egg yields individually recorded. At 37 weeks of age they were challenged by aerosol exposure to virulent IB virus. The egg production dropped significantly in the hens from flock A but not in the hens from flock C. On the farm, flock C showed a higher mean IB virus antibody titre four weeks after vaccination but titres rose in all three flocks indicating the presence of active IB virus infection. No differences in egg yields were found between the three farm flocks. PMID- 6266126 TI - [Laboratory trials of culturing BHK 21 C 13 cells in a roller using an enzymatic egg hydrolysate-based nutrient medium]. AB - Experiments were carried out to find the optimal conditions for the replication of BHK 21 C 13 cells in one 1 roller glassware with the use of a nutrient medium containing products of the enzymatic breakdown of white of egg. Studied was the sensitivity of these cells to the type C strain 'Hungary' of the foot-and-mouth disease virus. Two series of F. M. D. vaccines were produced, which proved to be sterile and innocuous for guinea pigs. Immunogenicity trials with regard to these animals revealed that the VD50 (vaccinal dose) values ranged from 0.12 to 0.26 cm3. PMID- 6266127 TI - [Complement fixation test act in the diagnosis of mucosal disease-virus diarrhea in cattle]. AB - Experiments were made to obtain a highly active antigen for the complement fixation test, using purification and concentration with methyl alcohol in a cell culture suspension of the causative agent of mucous disease-virus diarrhea. It was established that the CF test was sufficiently rapid and specific in the diagnosis of the disease in cattle. It proved instrumental in detecting complement-fixing antibodies in diseased and survived cattle, in calves with a latent infection and in cows with abortions. PMID- 6266128 TI - Immune response to experimental infection with bovine leukemia virus (BLV) in domestic and laboratory animals. AB - The immune response to cell-associated and cell-free BLV inoculation was studied in calves, lambs, rabbits and specific pathogen-free chickens. Inoculation of cell-associated or cell-free BLV failed to induce infection in rabbits and chickens (strain PDRC), but resulted in the infection of Holstein-Frize calves and of lambs, which exhibited a specific immune response over the entire observation period. Specific antibodies to glycoprotein and p24 fractions of BLV were detected in the infected animals. BLV could be recovered from serologically positive animals. PMID- 6266129 TI - Isolation of parainfluenza virus type 3 from a male patient with nonbacterial urethritis. PMID- 6266131 TI - Investigations on the circulation of enteroviruses in a children community. PMID- 6266130 TI - Investigations of the presence of serum antibodies to Epstein-Barr virus in patients with various tumors. AB - Serum samples from 150 patients with various malignant or benign tumors and from 20 clinically healthy subjects were tested by indirect immunofluorescence (IF) reaction for the presence of specific antibodies to Epstein-Barr-virus-determined viral capsid antigen (EB VCA). The IF test-carried out in multitest-slide EB3 and Raji cell preparations-revealed antibodies to EB VCA in 102 of the patients with tumors and in 4 of the healthy persons. PMID- 6266132 TI - Recombinant DNA technology. Some contributions to the isolation of vehicles. PMID- 6266133 TI - Attempts at the initiation of cell lines derived from uterine cervix carcinomas. PMID- 6266134 TI - Genes of human (strain Wa) and bovine (strain UK) rotaviruses that code for neutralization and subgroup antigens. PMID- 6266135 TI - Establishment of Sendai virus persistent infection: biochemical analysis of the early phase of a standard plus defective interfering virus infection of BHK cells. PMID- 6266136 TI - Transformation-enhancing factor(s) released from chicken Rous sarcoma cells: effect on some transformation parameters. PMID- 6266137 TI - SV40 defectives selected during low multiplicity passage on A172 human glioblastoma cells. PMID- 6266138 TI - Transformation with subgenomic fragments of feline sarcoma virus proviral DNA. PMID- 6266139 TI - Leukemogenic properties of AKR dualtropic (MCF) viruses: amplification of murine leukemia virus-related antigens on thymocytes and acceleration of leukemia development in AKR mice. PMID- 6266140 TI - Viable variants in VA-RNA, gene of an Ad2-Ad5 recombinant. PMID- 6266141 TI - A transcriptional map of the bacteriophage SPO1 genome. III. A region of early and middle promoters (the gene 28 region). PMID- 6266142 TI - Characterization of a papilloma virus from the European elk (EEPV). PMID- 6266143 TI - Characterization of a temperature-sensitive, DNA-positive, nontransforming mutant of simian virus 40. PMID- 6266144 TI - Preparation of autologous antiserum against SSV nonproducer cells and its partial characterization. PMID- 6266145 TI - Detection of a transformation-specific glycopeptide in SSV-infected cells. PMID- 6266146 TI - Growth of lambda rev in phage P2 lysogenic hosts. PMID- 6266147 TI - Expression of the syncytial (syn) phenotype in HSV-1, strain KOS: genetic and phenotypic studies of mutants in two syn loci. PMID- 6266149 TI - Repair of lesions which cause premature termination of transcription in chicken embryo cells irradiated with ultraviolet light. PMID- 6266148 TI - The genesis of Rous sarcoma virus messenger RNAs. PMID- 6266150 TI - The 28 S genomic RNA of avian sarcoma virus PRCII codes for the transformation specific polyprotein P105. PMID- 6266152 TI - SV40-53K antigen: a possible role for 53K in normal cells. PMID- 6266153 TI - Mapping of additional temperature-sensitive mutations (1600 series) on the genome of simian virus 40 by marker rescue. PMID- 6266151 TI - Chromatographic evidence that the AAA-coding isoacceptor of lysine tRNA primes DNA synthesis in murine mammary tumor virus. PMID- 6266154 TI - Balb/3T3 cells chronically infected with N-tropic murine leukemia virus continue to express Fv-1b restriction. PMID- 6266155 TI - Amplification of papovavirus defectives during serial low multiplicity infections. PMID- 6266156 TI - [Study of viral contamination of Japanese quail and cell cultures from their embryos]. AB - Agents identified as adenovirus CELO were isolated from organ suspensions of 1500 Japanese quails (JQ) in 4 experiments. No contaminating viruses were found in examinations of cell cultures prepared from the kidneys of 80 JQ. Negative results were obtained in examinations of 163 antigens from JQ organs in the COFAL test. Agents identified as mycoplasma were isolated in 16 cases from 736 specimens of the virus-containing fluid used for manufacture of measles virus. According to the results of the CFT, 59 antigens prepared from Japanese quail embryo cell cultures contained no oncornavirus antigens and were negative in the COFAL test. Among 1848 JQ sera examined for the presence of antibody to leukemia sarcoma complex viruses only 2 sera were found in 1976 to contain antibody to Rous sarcoma virus. No antibody to Marek disease virus in 414 serum samples or to Newcastle disease virus in 554 sera were detected. Among 500 sera tested 30.8% contained antibody to adenovirus CELO. PMID- 6266157 TI - [Detection of smallpox antibodies in human serum using the labeled-antibody technic]. AB - Ninety-seven samples of human sera with various amounts of smallpox antibody were simultaneously compared in ELISA and HI test, and 26 of them were also studied in NT. Alongside with HI and NT, ELISA was shown to be highly sensitive and reproducible, and useful for simultaneous examination of a large number of sera. PMID- 6266158 TI - [Isolation of herpes simplex virus in chronic meningoencephalitis]. AB - Virological examination of a patient suffering from chronic meningoencephalitis was carried out using serological and morphological methods. Strains of herpes simplex virus were isolated from the saliva, cerebrospinal fluid, and blood of the patient simultaneously in white mice and tissue culture. A rise in antibody titers to the isolate, its high neuropathogenicity in animal inoculation experiments, and the results of pathomorphological studies confirm the herpetic nature of the neuroinfection in this patient. Serological identification and investigation of biological properties of the virus showed it to belong to the 2nd antigenic type of herpes simplex virus. PMID- 6266159 TI - [Experimental infection of green monkeys with adenoassociated virus]. AB - Primary infection and reinfection with adeno-associated virus type 4 (AAV-4) was reproduced in green monkeys experimentally infected with AAV-4 in mixture with adenovirus. Wide dissemination of the satellite virus in animals was observed. AAV-4 and its antigen were detectable 5 to 23 days after inoculation. In monkeys infected with a mixture of AAV-4 and adenovirus or with one of them the infection was accompanied by a marked fever persisting from the 5th to the 20th day after inoculation. The infected monkeys showed an intensive rise of homologous antibody titer most marked on the 10th-15th day after inoculation with AAV-4. AAV-4 and its antigen were detected in smears from conjunctival and tonsillar mucosa, rectal specimens in the time course of the infectious process, as well as from the trachea, lungs, liver, spleen, intestines and kidneys of the sacrificed monkeys. Besides, AAV-4 antigen was found in cells of the tonsils and blood leukocytes of the sacrificed monkeys. No virus or its antigen were found in the brain and heart tissues. Virions of adeno-associated virus were found by electron microscopic examinations of kidney cells of one of 3 monkeys infected with AAV-4. PMID- 6266161 TI - [Relation between serum enzymes and articular radionuclide tests in the diagnosis of osteoarthrosis and rheumatoid arthritis]. AB - Serum enzymes and articular radionuclide tests have a restricted application in solving the current diagnostic and differential-diagnostic problems of present day rheumatology. The enzyme tests became positive in case of a high activity of rheumatoid arthritis, not objectivizing the articular degeneration. Their correlation with radionuclide tests of the patients with osteoarthrosis and the patients with rheumatoid arthritis is not elucidated. A juxtaposition was made of the serum enzymes with the articular radionuclide quantitative indices in 88 patients with rheumatoid arthritis with various clinical-laboratory activity, 88 patients with osteoarthrosis in various X-ray stages and 22 healthy controls. A correlation dependence was established between LDH, CPK, acid phosphatase, clearance effectiveness of articular cavity and the deposition of 99mTc pyrophosphate in knee joints of the patients with osteoarthritis and between gamm GT, alkaline phosphatase, acid phosphatase and radionuclide articular indices of the patients with rheumatoid arthritis. Those characteristics enabled the earlier overcoming of the diagnostic difficulties in those two basic rheumatic diseases. PMID- 6266160 TI - [Isolation of adeno-associated virus type 4 from a culture of green monkey kidney cells]. AB - In the process of biological control of uninfected green monkey kidney (GMK) cell cultures a thermostable hemagglutinating agent designated No. 5056 was isolated alongside with adenovirus-SV. By its antigenic properties the 5056 strain was identified as adeno-associated virus type 4 (AAV-4). In control of 574 specimens of GMK culture batches, 40 AAV-4 strains were isolated in the presence of a helper adenovirus. Some biological properties of the isolates and their resistance to certain physical and chemical treatments were studied. Two isolates of the satellite virus were examined in the electron microscope. A correlation between the rate of AAV-4 isolation from GMK cultures and the presence of complement-fixing antibody to AAV-4 in monkey sera was observed. PMID- 6266162 TI - [Current treatment concepts in chronic heart failure]. PMID- 6266163 TI - Alkalinization therapy for tricyclic antidepressant overdose. PMID- 6266165 TI - [Detection of rotavirus in infants with acute gastroenteritis (author's transl)]. AB - Throughout 1978, stools of Austrian infants and young children with gastroenteritis were investigated for the presence of viruses by means of electron microscopy. Rotavirus was found in 131 out of 590 children. Adenoviruses were observed in 18 cases. The viruses were detected more often during the cold season, particularly in children up to two years of age. PMID- 6266164 TI - [Long-term survival after pulmonary resection in bronchogenic carcinoma (author's transl)]. AB - 25 patients with bronchogenic carcinoma, who had undergone pulmonary resection between 1950 and 1964, were re-examined after a survival time of between 15 and 29 years. There was no relation between the long survival time and the duration of preoperative symptoms, the smoking habits prior to the operation or the localization of the tumour. The histological classification revealed that 14 patients had suffered from squamous cell carcinoma and 11 from large cell carcinoma. There was no case of adenocarcinoma nor of small cell carcinoma. In 7 patients tumour cells were demonstrable in the resected lymph nodes and in at least 2 cases the edge of the resected tissue was not tumour-free. In one case the blood vessels were invaded by tumour cells. PMID- 6266166 TI - [Current status and future developments in chemotherapy of advanced epithelial ovarian cancers (author's transl)]. AB - In the management of advanced epithelial cancers of the ovary the importance of prognostically significant factors is well established. The remission rates with the drugs most commonly used are stated. Patients with a complete remission show a marked increase in survival time. The importance of prior chemotherapy in relation to a second or third line of treatment is discussed. Immunological test series in combination with chemotherapy are undergoing controlled investigations. PMID- 6266167 TI - [Angiographic investigation with parathyroid hormone administration as functional gauge of liver blood flow (author's transl)]. AB - Parenteral administration of parathyroid hormone causes dilatation of the main hepatic artery adn the intrahepatic branches, as demonstrable on coeliacography. This applies to healthy persons as well as to patients suffering from cirrhosis of the liver. When hormone is given intraarterially, i.e. into the coeliac trunk, the effect on the hepatic arteries is stronger than after intravenous administration. No effect can be be shown on the splenic, upper mesenteric or gastroduodenal arteries. The reaction of the hepatic arteries to parathyroid hormone seems to be a good parameter of the degree of dilatory capacity of these vessels in cirrhosis. Relevant conclusions can probably be drawn as to the prognosis of porto-systemic shunt operations and their indication. This haemodynamic hormone effect, the cause of which is still unknown enabled better visualisation of primary liver tumours on coeliacography. PMID- 6266168 TI - [The significance, place and accuracy of sonography in the diagnosis of liver disease (author's transl)]. AB - Ultrasonography of the liver as a non-invasive examination technique has been integrated within the recent years amongst the methods in routine use for the clinical diagnosis of liver diseases. The reliability of this technique is comparable to scintigraphy and computer-tomography. Side-effects are practically non-existent, whilst cost and time expenditure are markedly lower than with these other techniques. Sonography is indicated in any suspected diffuse or circumscribed pathological lesion of the liver. Furthermore, sonography is performed for the detection of ascites, perihepatic abscesses to evaluate the mobility of the diaphragm and in any case of jaundice of unknown aetiology. In the following study the referral diagnosis, ultrasonic diagnosis and final diagnosis were compared in 26 patients referred for ultrasonic diagnosis. In 22 out of the 26 patients full agreement was obtained between ultrasonic diagnosis and the final diagnosis. In 2 cases liver disease was suspected on ultrasonic examination, but the specific diagnosis was missed. A lack of agreement occurred in only 2 patients with respect to ultrasonic and final diagnosis. This study demonstrates the high accuracy of ultrasonic diagnosis in liver diseases. Ultrasonography, scintigraphy and computer tomography give similar results. In some cases, however, clinical diagnosis may be optimized by a combination of all available methods. PMID- 6266169 TI - Nongonococcal urethritis and other selected sexually transmitted diseases of public health importance. Report of a WHO Scientific Group. PMID- 6266170 TI - Disulfiram neuropathy. PMID- 6266171 TI - Pregnancy testing-principles and practice. PMID- 6266172 TI - [Disturbed sodium and calcium exchange in erythrocytes of spontaneously hypertensive rats (author's transl)]. AB - In red blood cells of spontaneously hypertensive and of normotensive rats intracellular NA+ activity (a(i)Na), Na+ concentration (]Na+]i) and Ca2+ activity (a(i)Ca) were measured by ion-selective electrodes and flame photometry, respectively. In spontaneously hypertensive rats a(i)Na and a(i)Ca were significantly elevated as compared with the normotensive controls, whereas [Na+]i showed no significant difference. In hypertensive animals a(i)Na, exceeded [Na+]i, in normotensive rats a(i)Na was lower than [Naf+]i. From these results it can be concluded: (1) In spontaneously hypertensive rats the transmembraneous distribution of free Na+ is altered, (2) an elevation of intracellular free Ca2+ may contribute to increased vascular contractility in hypertensive animals, (3) the described abnormalities may be caused by a lowered binding-capacity of intracellular macromolecules for Na+ and Ca2+. PMID- 6266173 TI - [Pathogenic viruses and the problem of environmental protection]. PMID- 6266175 TI - A study on the combined action of CO and HCN in terms of concentration-time products. AB - Acute toxicity at single and combined exposures of CO and HCN was studied on rats in terms of concentration-time product (ppm . min) necessary to kill animals (lethal CT). The animal was exposed individually to test gas in an animal chamber made of transparent plastics, and test gas was made in gas chamber connected to the animal chamber by a wide and short piece of plastic tube. HCN was produced by addition of NaCN solution to H2SO4 and in case of CO exposure, various amounts of pure CO were introduced. During exposure, gas samples were frequently taken. After exposure, blood sample was withdrawn from the right side of the heart. CO concentrations in the gas and blood were determined gas chromatographically. HCN in the gas sample was measured spectrophotometrically, after being absorbed into NaOH solution in a glass vessel devised by our laboratory. At single exposures, mean lethal CT for CO was 78,000 +/- 22,000 and for HCN was 4,700 +/- 940. In combined exposure, various combinations of CO and HCN were used. A fractional CT, defined as a ratio of CT to lethal CT, multiplied by 100, was calculated for each gas. A linear relationship between fractional CTs of HCN and CO was considered to show a simple additive action between the two gases. The sum of both fractional CTs averaged 100 +/- 26. On the other hand, linear relation was not observed between blood levels of the two toxicants at death. PMID- 6266174 TI - [Diagnosis and therapy of hepatoblastoma. Successful treatment of an inoperable hepatoblastoma and review of the literature (author's transl)]. AB - A review of the literature shows minimal success in relation to the treatment of hepato-blastoma. Recent improvements have been related to better techniques of liver resection. No final therapeutic recommendations can be made but prophylactic chemotherapy is indicated. The authors present a surprisingly successful patient who had a non-resectable hepato-blastoma and who is alive 8 years later without symptoms. In spite of radiotherapy, and chemotherapy there have been no obvious somatic changes which could be attributed to the treatment. The effect of treatment on the gonads is a feature that will have to be considered at a later date. PMID- 6266176 TI - Chronic effects of some drugs on histopathology and lipid content of liver in rabbits. PMID- 6266177 TI - [Benign tumours of the female breast (author's transl)]. AB - In a period of 25 years 289 women suffering from benign tumours of the breast were seen at our Dept. This number comes up to a percentage of 20.5 of all female patients treated in this time for diseases of the mamma. Pathology, symptoms, treatment and prognosis of benign tumours of the female breast are dealt with. PMID- 6266178 TI - [Role of the hypothalamus and pituitary gland in the development of pancreatic islet sensitivity to glucose in fetal rats]. AB - Differences in the pattern of the development of three enzymes of the plasma membrane have been established. The activity of Na, K-ATPase progressively increases, that of adenylate cyclase decreases, whereas the activity of 5 nucleotidase undergoes only slight changes during embryogenesis. Differences between these enzymes were also found with respect to the development of their sensitivity to the regulatory effects of catecholamines. Adrenaline reactivity of adenylate cyclase may be detected already in embryogenesis; it is lower than that in definite muscle tissue increasing during further ontogenesis. Catecholamine reactivity was not found in Na, K-ATPase and 5-nucleotidase up to the 17th day of incubation of chick embryos. The effect of adrenalin was observed at later stages of ontogenesis, it may be initiated by exogeneous cAMP and protein kinase. At postembryonic stages, similarity in the behavior of these enzymes was found with respect to the presence and pattern of their reaction to adrenalin (stimulation), as well as with respect to temporal dynamics of the effect. The data obtained indicate the existence of close connections between these enzymes, which are realized in the sequence adrenoreceptor-adenylate cyclase-cAMP-protein kinase effector proteins. PMID- 6266179 TI - [Role of membrane lipids in the functioning of the hormone--sensitive adenylate cyclase (a review)]. PMID- 6266180 TI - [Indices of the state of the pituitary-adrenal system in hereditary myopathies]. PMID- 6266181 TI - Characteristics of Ba2+-stimulated insulin release with special reference to pancreatic beta-cells sensitized by cyclic AMP. AB - Ca2+-dependent processes are activated by Ba2+ in a variety of biological systems. When Ca2+ was replaced by equimolar amounts of Ba2+ there was a marked increase in insulin secretion from beta-cell-rich pancreatic islets microdissected from ob/ob-mice. At both 3 and 20 mM glucose Ba2+ stimulated insulin release in a concentration-dependent manner, being less stimulatory at high concentrations. The stimulatory effect of Ba2+ on insulin release is similar to that of Ca2+ in being more pronounced and reached at lower concentrations when the beta-cells were sensitized by cyclic AMP. However, both glucose oxidation and utilization were suppressed when Ca2+ was replaced by equimolar amounts of Ba2+. Ba2+-stimulated insulin release resembled physiological secretion initiated by Ca2+ in being inhibited by L-epinephrine, pentobarbital and a low oxygen tension. PMID- 6266182 TI - Beta-cell function in isolated human pancreatic islets in long-term tissue culture. AB - Human pancreatic islets were isolated by collagenase treatment of pancreatic tissue obtained from 27 individuals aged 12 to 69 years. The islets were maintained free floating in tissue culture medium RPMI 1640 supplemented with calf or human serum. In two cases the insulin production was followed up to nearly two years. The insulin production rate of the individual islet preparations varied between 0.2 and 8 ng per islet per day. No significant correlation with donor age or sex was found. The glucose concentration in the medium influenced the insulin release in a dose dependent manner. The acute response of the cultured islets to glucose was evaluated both by batch incubation and by perifusion. Both in the acute and the chronic experiments maximal insulin release was found at 10 mM glucose. In conclusion, these experiments indicate that viable islets of Langerhans can be obtained from adult human pancreatic tissue and that their beta-cell function can be maintained for up to two years. The variation in insulin production rate could not be ascribed to age or sex and may reflect both physiological and methodological factors. PMID- 6266183 TI - [Urothelial tumors of the upper urinary tract]. PMID- 6266184 TI - Value of sputum cytology in the differential diagnosis of alveolar cell carcinoma from bronchogenic adenocarcinoma. AB - A total of 90 cases in which a cytologic diagnosis of pulmonary adenocarcinoma has been previously made by consecutive sputum cytology were reviewed in order to estimate the possibility of a correct differential diagnosis of alveolar cell carcinoma (bronchioloalveolar) from bronchogenic adenocarcinoma. The diagnosis by sputum cytology in all cases was correlated with data from a subsequent biopsy, operation or autopsy. Using certain specific differential diagnostic cytologic parameters, striking differences were noted in the exfoliated cells in sputum samples; these related to cell size, clustering effects, pleomorphism, mucin production, cytoplasm, nuclei and nucleoli. Based on the observations made in this study, it is suggested that sputum cytology is not only a valuable method of detecting malignant cells but can also be quite useful to correctly type all cases of alveolar cell carcinoma and 93.75% cases of bronchogenic adenocarcinoma. PMID- 6266185 TI - Potentiation of prostaglandin E2-induced release of LH by the prostaglandin analogue, 7-oxa-13-prostynoic acid. AB - The prostaglandin (PG) analogue 7-oxa-13-prostynoic acid (7-OPA) was infused into a lateral ventricle of the brain of adult male rats and the effect of the analogue on the subsequent stimulation of LH release by intraventricular infusion of PG's was determined. Pretreatment of the animals with 44- 132 micrograms of 7 OPA potentiated the stimulatory effect of 2 micrograms PGE2 on the release of LH but the analogue alone had no effect on the hormone secretion. The minimal effective dose of PGE2 was determined to be within the range 0.01-0.05 micrograms and it was found that priming with 132 micrograms of 7-OPA caused a formerly sub threshold dose (0.01 micrograms) of PGE2 to become an effective stimulus for the release of LH. In contrast to its potentiating effect on PGE2-induced LH release 7-OPA did not alter the stimulatory action of PGF2 alpha (2 micrograms) on the secretion of LH. 7-OPA had no effect on LRH-induced release of LH indicating that PG analogue acts at a suprapituitary site to enhance PGE2-induced LH release. The potentiating effect of 7-OPA may be exerted at a binding site for PGE2 in the brain and the results suggest the existence of a different binding site for PGF2 alpha. The possibility also exists that 7-OPA inhibit metabolic inactivation of PGE2. PMID- 6266186 TI - Gonadotrophin release by gonadotrophs incubated with gonadotrophin-releasing hormone is independent of intracellular cAMP accumulation. AB - Rat pituitary cells were dispersed with trypsin and separated by sedimentation at unit gravity. The distributions of prolactin (Prl), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were determined, and two enriched cell populations (mammotrophs and gonadotrophs) were subsequently cultured. During a 4 h incubation, gonadotrophin-releasing hormone (GnRH) stimulated the release of LH and of FSH by both the unfractionated population and the enriched gonadotrophs; the magnitude of this stimulation increased with the length of the pre-culture periods, and the amount of LH released into the medium correlated strongly with the amount of FSH, whatever the length of the pre-culture period. The cellular cAMP content was also enhanced during the 4 h incubation, but no correlation was found between the hormone release and the cAMP accumulation. Furthermore, during the first 30 min of incubation with GnRH there was no increase of cellular cAMP, whatever cell population used. We conclude that the gonadotrophin release was independent of the cAMP accumulation observed in pituitary cells several hours after stimulation by GnRH; consequently, the late increase in the nucleotide is suggested to be a non-specific secondary process. PMID- 6266187 TI - Micromethod of human thyrocyte cultures for detection of thyroid-stimulating antibodies and thyrotrophin. AB - The activation of adenylate cyclase of human thyrocytes in primary cell cultures and the release of cAMP into the medium are used to detect thyrotropin (TSH) and thyroid-stimulating antibodies (TSAb) in sera of patients with Graves' disease. Tissue digestion and cell dispersion are performed using a neutral protease of Bacillus polymyxa (Dipase II), which harvests more vital thyrocytes than does trypsin. The cells show an enhanced response to stimulation. The efficiency of the cell preparation and cultivation is increased by using microtest plates instead of culture flasks. By this minimization only 0.6-1.8 X 10(6) cells are needed to evaluate a single sample. Cyclic AMP concentrations are measured directly in the supernatant culture medium by a competitive protein binding assay with charcoal separation. The minimal detectable dose of bTSH is about 10 microU/ml. With increasing doses of bTSH cAMP concentrations rise to a peak at about 50 to 100 mU/ml, beyond which there is a gradual decrease of cAMP indicating negative cooperativity in the activating mechanisms. The 'long-acting thyroid stimulator' effect of TSAb is reflected by a protracted increase of cAMP to its maximal value. All 41 sera of hyperthyroid patients with Graves' disease were TSAb-positive, whereas sera of patients with toxic nodular goitre and euthyroid controls were TSAb-negative. PMID- 6266188 TI - Plasma cyclic nucleotides and plasma catecholamines before and after prolonged treatment with clonidine in hypertensive patients. AB - The effect of standing and physical exercise and catecholamines and cyclic nucleotides in plasma was measured in 8 patients with essential hypertension under standardized conditions before and after prolonged treatment with clonidine. Before clonidine medication noradrenaline, adrenaline and cyclic AMP (cAMP) increased in response to standing and bicycling for 20 min. No significant correlation was found between their absolute levels nor was the increase in cAMP following exercise correlated to the increase in noradrenaline. Standing and physical exercise were without effect on cyclic GMP (cGMP). Clonidine reduced the plasma noradrenaline concentration in supine position and the noradrenaline and the adrenaline response to standing and exercise. Plasma cAMP was uneffected by clonidine under basal conditions but the response to exercise was slightly reduced initially. During clonidine there was a positive correlation between the plasma levels of cAMP and noradrenaline following work. Clonidine produced an increase in plasma cGMP in supine position, immediately prior to bicycling and after 5 min of exercise. PMID- 6266189 TI - Immunohistological demonstration of ACTH-like immunoreactivity in the foetal adrenal medulla in the 23rd week of gestation. AB - By an indirect immunofluorescence technique and silver impregnation, cells reacting with anti-1-18 ACTH antiserum were demonstrated in the foetal adrenal medulla only in the 23rd week of gestation. They were not found in the foetal adrenal glands before the 23rd week or after 29th week and after birth. The result was confirmed by immunohistological examination using anti-1-18ACTH rabbit IgG purified by affinity chromatography. No cells in the foetal adrenal medulla in the 23rd week of gestation were stained positively by using anti-beta-MSH and anti-beta-endorphin antisera. This finding suggested, therefore, that the synthetic mechanism of ACTH-like immunoreactivity in the foetal adrenal glands was different from that in the pituitary. In view of the findings that some phaeochromocytoma contained ACTH-like immunoreactivity, the present study suggested that the origin of the phaeochromocytoma congested that the origin of the phaeochromocytoma containing ACTH-like immunoreactivity may be the cells of the foetal adrenal medulla in about the 23rd week of gestation. PMID- 6266191 TI - Tissue culture and scanning electron microscopy of breast carcinoma 'cell line MCF-7' from pleural effusion. AB - The surface ultrastructure of tissue-cultured cells derived from the pleural effusion of metastatic scirrhous breast carcinoma in the human MDF-7 cell line was studied by scanning electron microscopy. It was found to form monolayers of various colonies or collections of cells which were either separate or intimately adherent. The surface ultrastructure of the cells was found to be exclusively formed of microvilli. Data suggesting a diagnostic significance of microvilli in cancer cells were discussed. Observations were made which point to the existence of a compensatory absorptive functional activity exerted by the microvilli. PMID- 6266190 TI - [Use and results of the microscope photometry in the virology (author's transl)]. AB - Labelled preparations are scanned fluorometrically and absorptionsphotometrically qualitative and quantitative evaluation. Thereby dynamic characteristics can be found which may serve as markers for different virus types. The titre, probability of detection and the required dilution for complete detection of antigens can be determined. The microscope photometry is applicable for screening of potential virostatica as well as topographic analyses of virus synthetisizing cells. The distribution of computer operated scanning photometry is ensued by digital plotter as a 3 dimensional or mosaic print out. Moreover, cadastres of the immunity can be obtained by the fluorometric technique. PMID- 6266192 TI - [Leprosy - - an overview]. PMID- 6266194 TI - Rapid assay of herpes simplex virus sensitivity to drugs. AB - A 16 h immunofluorescence microplaque reduction assay for herpes simplex virus (HSV) was compared with a plaque reduction assay to assess its feasibility as a rapid technique for determining viral sensitivity to drugs. A drug-sensitive HSV strain (HSV-1 Patton) and a drug resistant strain (HSV-1-P-ACG-R), both grown in cell cultures, were compared against serial dilutions of adenine arabinoside (Ara A) and acycloguanosine (ACG). Similar studies were done with virus obtained directly from experimentally infected rabbit corneas. The microplaque assay yielded results similar to the plaque assay and has the advantage of speed, which may be useful in clinical situations. PMID- 6266193 TI - Pathology of rabies: a light- and electron-microscopical study with particular reference to the changes in cases with prolonged survival. AB - Light- and electron-microscopical studies were conducted on necropsy material from six cases of rabies encephalitis including three with the unusual feature of surviving for over 14 days as a result of intensive medical care. This included administration of antiviral agents and interferon inducers and prevention of hypoxia by intermittent positive pressure ventilation. In all these cases, typical Negri bodies were demonstrated. Inflammatory reaction was absent or minimal. Unlike the cases with short survival where Negri bodies were infrequently seen and restricted mostly to the hippocampus, in cases with prolonged survival, they were present in large number, widely distributed throughout the grey matter of the brain. The associated inflammatory reaction in these cases, however, did not keep pace with the increase in number of inclusion bodies. Peripheral neuritis was observed in two of these cases, which also showed myelitis involving the cervical region and inflammation of dorsal root ganglia. One of them showed necrosis and severe inflammation of the lower cervical sympathetic ganglion. An electron-microscopical study conducted in four cases showed three forms of the inclusion body in the cytoplasm of neurons. PMID- 6266195 TI - Sensory hairs and filaments rods in vestibular hair cells of the waltzing guinea pig. Organization and identification of actin. AB - The waltzing guinea pig suffers from hereditary deafness and vestibular disorder. In vestibular organs, hair cells of Type I develop pathologically and will eventually degenerate. They show fusion of sensory hairs, protrusion of the cuticular plate and contain a rod-shaped inclusion body. With fixation techniques designed to preserve proteins it is shown that this rod has a filamentous substructure reminding one of stereocilia. The packing density of the filaments is similar and circular packing patterns are seen within both structures. However, the rod has an irregular cross-section, as opposed to the circular circumference of stereocilia. The filaments in the rod were identified as containing the protein actin (as those in the stereocilia) by decoration with sub fragment S-1 of myosin. All filaments in the rod have an identical functional polarity, pointing up from the nucleus towards the cuticular plate. This is contrary to that seen in stereocilia, which have filaments pointing down towards the cuticular plate. It is concluded that the rod is not developed by random polymerization of actin but is the result of co-ordinated assembly reminiscent of that which gives rise to stereocilia. The genetic defect appears to be related to mechanisms which determine the site of nucleation and the functional orientation of actin filaments during development. PMID- 6266196 TI - Comparison of three methods for measuring nasal mucociliary clearance in man. AB - Three techniques for studying nasal mucociliary clearance have been compared in 20 normal subjects, aged 19 to 26. Three different tracers used were deposited on the septum or the nasal floor. The transport rate of a 250 micron anion resin particle tagged with 99mTc was measured over a distance of 3.5 cm. This method was used as reference. The transport time of saccharin was measured when the subjects tasted its sweetness on swallowing. The transport time of 600 micron aluminium discs was measured by observing their arrival at the pharynx. For each method, duplicate measurements were carried out over a 24 hour period. Despite the large variations in the results from one day to the next, a significant negative correlation (r = -0.59, p less than 0.001) was observed between the transport rate of the radioactive particles and the transport time of the saccharin. The daily variations in nasal clearance for these two methods were also significantly correlated (r = -0.53, p less than 0.02). These results validate the suitability of the saccharin method as a simple screening test for detecting abnormally low values of nasal mucociliary clearance. In our group of 20 subjects, 5 were characterized by a low nasal mucociliary clearance, whichever method was used. PMID- 6266197 TI - A mixed tumor of the omentum majus in an adult with discussion related to hepatoblastoma. AB - A mixed tumor of the omentum majus found at autopsy of a 28-year-old man with a huge liver tumor is described. The primary tumor was identified in the omentum majus by macroscopic, histologic and electron-=microscopic observations. The tumor was finally diagnosed as a mixed tumor which resembled a hepatoblastoma consisting of immature and embryonal types of epithelial component and of mesodermal tumor including hemangioma, osteoid and myxomatous tissues in the primary lesion. Widespread multiple metastases of the epithelial component mainly to the liver, and partially in the lungs, diaphragm and lymph nodes were noted. The levels of alpha-fetoprotein and carcinoembryonic antigen were within normal limits, but the epithelial component showed a resemblance to primitive hepatocytes. This tumor was discussed related to hepatoblastoma in an adult, with the features compatible with description of the same tumors reported previously in the literature. PMID- 6266198 TI - Extracted protective antigen of Bordetella pertussis. I. Preparation and properties of the solubilized surface of components. AB - Bordetella pertussis microorganisms were treated with several extracting agents followed by ultracentrifugation to remove particulate matter. Analysis of the resulting supernatants by SDS gel electrophoresis showed one major component after simple salt extraction, and much more complex, although consistent pattern following detergent treatment. The yield of the solubilized protein in detergent extracts exceeded by far the values recorded for salt extracts. In order to prevent irreversible precipitation of the solubilized proteins upon removal of the denaturing agent, a novel procedure was developed. After extraction with urea salt, the solubilized material was absorbed on a mineral carrier prior to the separation of the denaturing agent. The resulting absorbed vaccine was highly potent in the mouse-protection test, whereas the toxic reactions, elicited upon injection into experimental animals, were reduced in the comparison to the starting material. This diminished reactogenic potential was accompanied by the partial loss of the leukocytosis-promiting factor, whose activity was greatly diminished by urea-salt at alkaline pH-values. The procedure described may be applied to large-scale processing of Bordetella persussis microorganisms. Clinical trials now in progress should confirm or rebut the thesis that increased tolerability of the product, inferred from animal experiments, is reflected by fewer adverse reactions in humans. In the former case, the detergent extract vaccine may constitute a realistic alternative to conventional whole-cell vaccines against whooping-cough. PMID- 6266199 TI - [Pharmacological studies on 14-deoxy-11, 12-didehydroandrographolide-3, 19 disuccinate. I. Anti-inflammatory activity (author's transl)]. PMID- 6266200 TI - [A study on the chemical constituents of the leaves of the Ilex pubescens Hook et Arn var glaber Chang. III. Elucidation of the structure of glaberide I. A new lignan compound (author's transl)]. PMID- 6266201 TI - Recent progress in the field of gastrointestinal peptide hormones. AB - This is a critical survey of the results of recent investigations on gastrointestinal peptide hormones. The following subjects are dealt with: molecular homology and heterogeneity; mechanism of action of gastrointestinal peptide hormones; hormone-receptor binding; trophic effect; metabolism of gastrointestinal peptide hormones; relationship between humoral and neural regulation in the nervous system. PMID- 6266202 TI - Long lasting amplification and deformation of thyroid receptors after thyrotropin (TSH) and gonadotropin (GTH) treatment of chickens in the foetal period. AB - Gonadotropin or TSH treatment of the chick embryo influences the T4 production of the one-month-old animal if TSH is given on a second occasion. Hormone treatment on the 8th day of life was ineffective, while previous treatment of the 12-day old embryo resulted in a significantly more pronounced elevation of serum T4 level compared to the control when provoked by TSH in the one-month-old animal and a significant reduction in the animals subjected to gonadotropin pretreatment. PMID- 6266203 TI - Cyclic nucleotides do not mediate excitability-suppressing cellular action of progesterone in the rabbit myometrium. AB - Uterine cAMP and cGMP levels were measured to radioimmunoassay in progesterone (P) dominated 25-day pregnant (Pr) and estrogen dominated post partum (Pp) rabbits, and 1, 3, 6, 12 and 24 hours after P treatment (10 mg i.m.) of Pp animals, simultaneously with changes in uterine smooth muscle excitability. Uterine cAMP level was similar in the Pr and Pp rabbits while cGMP concentration was significantly higher in the Pr uterus. P treatment significantly increased superficial Ca2+-binding and decreased electrical (field stimulation) and pharmacological (oxytocine, prostaglandin F2 alfa) excitability of Pp uterus after a latency period of 8--12 h. Uterine cAMP level did not change while cGMP level increased following P treatment. However, the significant elevation of cGMP was preceded by suppression of smooth muscle excitability. The data suggest that cyclic nucleotides are not involved in the excitability-suppressing cellular action of P in the rabbit uterus. PMID- 6266204 TI - Reconstitution of chromatin at physiological ionic strength and regulation of transcription of the reconstituted chromatin. AB - Rat liver and simian virus 40 (SV40) chromatin were reconstituted in vitro under physiological conditions of ionic strength and temperature. The nucleosome assembly under the conditions was mediated in the presence of chromatin extracts, rich in nicking-closing activity, from rat liver or cultured CV-1 cells. The frequency of nucleosome assembly on DNA was dependent on both the incubation time and the weight ratio of histone to DNA. The regulatory effects of host cellular histones on the transcription of SV40 DNA were investigated by using reconstituted SV40 chromatin containing or lacking histone H1. The cellular histones composing the chromatin were prepared from permissive CV-1 cells. Transcription of chromatin was analyzed in vitro using Escherichia coli DNA dependent RNA polymerase. The rate of incorporation of ribonucleoside triphosphates into RNA synthesized on SV40 chromatin containing Hl as the template was 5 to 10% of the rate for RNA synthesized on supercoiled SV40 DNA. The rate of incorporation for SV40 chromatin lacking Hl was approximately 40 to 50% of that for SV40 DNA. RNA products transcribed from both these chromatin and SV40 DNA were fairly homogeneous 16 to 28S species with several identical peaks. PMID- 6266205 TI - A different distribution of corticotropin releasing factor and arginine vasopressin contents in the hypothalamic nuclei after estrogen administration. AB - The distribution of corticotropin releasing factor (CRF) and arginine vasopressin (AVP) in hypothalamic nuclei were examined in control and estrogen-treated female rats. CRF activity was measured using monolayer cultured rat anterior pituitary cells and AVP by radioimmunoassay. Hypothalamic nuclei were punched out according to the method of Palkovits. The distribution of CRF activity in 5 different hypothalamic nuclei was similar to that of AVP in intact female rats. CRF activity in hypothalamic nuclei, pituitary ACTH content and plasma ACTH levels in estrogen-treated rats were not significantly different from those in control rats. However, significant elevation of AVP content was observed in the supraoptic and paraventricular nuclei of estrogen-treated rats. These results indicate that CRF and AVP are distributed in similar hypothalamic nuclei, but that they are not identical. PMID- 6266206 TI - Free light chains of immunoglobulins in serum from patients with rheumatoid arthritis, sarcoidosis, chronic infections and pulmonary cancer. AB - Free light chains of immunoglobulins were measured in serum from 181 patients with rheumatoid arthritis (RA), sarcoidosis, pulmonary tuberculosis, pulmonary cancer and chronic bronchitis, i.e. patients with long-term stimulation of the immune system. Increased concentrations of light chains were found in patients with active sarcoidosis, and the light chain level appeared to be a marker of disease activity in sarcoidosis. The mean (+/- S.D.) concentration of kappa plus lambda chains in active sarcoidosis of more than two years' duration was 38.3 +/- 13.7 mg/l, that is twice the concentration of 19.4 +/- 5.5 mg/l found in normals. Some patients with seropositive RA also had increased serum values. The light chain concentrations in seropositive RA were correlated to the severity of the disease measured by clinical staging and laboratory tests. A modest increase in light chains was observed in one patient with tuberculosis, and in two patients each with chronic bronchitis and pulmonary cancer. PMID- 6266207 TI - The heart cell: some metabolic aspects of cardiac arrhythmias. AB - The maintenance of normal electrical activity in the myocardium is an ATP dependent process. Consequently failure to maintain the tissue reserves of ATP above a critical level, as occurs during ischaemia and post ischaemic reperfusion, results in the development of ionic imbalance. The ions involved include Na+, K+, Mg2+. Under conditions of low flow ischaemia an accumulation of K+ in the T-tubules may account for the genesis of some of the arrhythmias that occur during the ischaemic episode. Electrical uncoupling, another later event in an ischaemic episode, is probably due to an intracellular accumulation of Ca+. The contribution of an altered pattern of electrolyte distribution to the genesis of arrhythmias during myocardial ischaemia is discussed, with reference to the mechanisms whereby these ionic imbalances can be minimized or prevented. PMID- 6266209 TI - Rat undercut cortex as a model for the study of central amino acid transmission. PMID- 6266208 TI - IgG-Fc-binding receptors in cells abortively infected, or transformed, by human cytomegalovirus. AB - Abortive human cytomegalovirus (HCMV) infection of normal hamster cells is accompanied by formation of cytoplasmic and surface receptors for the Fc portion of nonimmune IgG molecules. The process requires RNA and protein synthesis but no DNA synthesis. The surface receptors are detectable only transiently, in a small proportion of the cells. The receptors are also present in cells transformed by HCMV in vitro (87-TRH-5 and CX-90-3B cell lines) as well as in cells of lines TSC 1 and TSC-2 from tumours induced by these cells. Consequently, the indirect immunofluorescence test performed with sera containing no HCMV antibodies may give a positive reaction in the cytoplasm and/or cell membrane of the transformed cells. PMID- 6266210 TI - GABA systems and behavior. PMID- 6266211 TI - Release of endogenous GABA from the rat brain: methodological aspects and the effects of catecholamines. AB - The release of endogenous GABA from the striatum, the substantia nigra and the ventral thalamic nucleus was measured in push-pull canula perfusates with high pressure chromatography and fluorimetric detection. The release of GABA per min is dependent on the flow rates, when low perfusion rates were applied. The GABA release was enhanced by K+ (maximal effect at 50 mM). The effects of various drugs added to the perfusion medium was measured. Imipramine, propranolol and other lipophilic bases (10 microM) enhanced the GABA release in the thalamus. Dopamine (DA), noradrenaline (NA), isoprenaline, clonidine and dibutyryl cyclic AMP decreased the GABA release from the striatum. Haloperidol blocked the effect of DA, but not that of NA. Stimulation of the locus coeruleus decreased GABA output. Destruction of striatal GABA-ergic neurons by kainic acid did not lead to a decreased number of NA-receptors as measured by the formation of cyclic AMP. The results indicate that both catecholamines influence GABA release and that DA and NA act at different receptors. The beta responses are mediated by beta adrenoceptors that are not confined to striatal GABA neurons. PMID- 6266212 TI - Receptors for the excitatory amino acids. AB - 1. Pharmacological evidence indicates that excitatory amino acid receptors are of three types: (a) glutamate/quisqualate-activated, GDEE-antagonized, (b) NMDA activated, D alpha AA-antagonized, and (c) kainate-activated with no known specific antagonist. 2. Some agonists can activate both types (a) and (b); and other antagonists can affect more than one class of receptor. 3. The GDEE sensitive receptors accept molecules in which the distal carboxyl-amino nitrogen distance approaches 0.2nm, while D alpha AA-sensitive receptors react with molecules in a more extended configuration. The "folded" receptor appears to have a higher affinity for its ligands in cases where molecules theoretically could react with either type. 4. D-glutamate can act as an agonist at the "extended" receptor and an antagonist of the "folded" type. 5. Kainate receptors appear also to be "extended" receptors perhaps physiologically activated by glutamate, but differ from those which are blocked by D alpha AA. We are grateful to Drs. J. Davies and J.C. Watkins for sending us manuscripts prior to their publication. H. McL is supported by the Medical Research Council of Canada. PMID- 6266213 TI - Possible role of divalent cations in amino acid responses of frog spinal cord. PMID- 6266215 TI - Amino acids and neurotransmission in rat cerebellar cortex. PMID- 6266214 TI - GABA receptor functions in cultured mouse spinal neurons. PMID- 6266216 TI - Physiological study of amino acid uptake and receptor desensitization: the GABA system in dorsal root ganglia. AB - GABA applied under microscopic vision (x320) to neurones of isolated DRG, triggers a depolarizing outflow of Cl-, as seen in intracellular recordings of large somata with myelinated fibres. Group C neurones have now also been examined with respect to diversity of GABA receptors. Cells of small diametre (less than 30 micrometers) responding to stimulation of slow conducting, (less than 2.5 m/sec) unmyelinated C fibres were studied for 2 reasons: 1) GABA probably depolarizes nerve endings and C fibres but conductance changes have not been determined, 2) the inference that, unlike group A, the group C neurones show an additional response to GABA by reducing the net influx of Ca++ during action potentials. As a first step in comparing group A with C neurones, it was found that all ganglion cells responded similarly to GABA with Cl--dependent depolarization and a rapid desensitization. This conclusion relies on combined physiological and pharmacological data and also on autoradiographs of glial GABA uptake. Results are considered to reflect direct actions of GABA on neuronal membranes and to be independent of secondary effects due to Na+-dependent transport of GABA into glia. PMID- 6266217 TI - Uptake inhibitors, amino acids, and spinal neurones. PMID- 6266218 TI - Structure/activity studies at a baclofen-sensitive, bicuculline-insensitive GABA receptor. PMID- 6266219 TI - The neurohypophysial GABA system. PMID- 6266220 TI - Synaptic transmission in crustacean muscle: effects of elimination of the inhibitor fiber on excitatory transmission. PMID- 6266221 TI - Amino acid actions in invertebrate nervous systems. PMID- 6266222 TI - Receptors for excitatory amino acids: binding studies and stimulation of cyclic GMP levels. AB - It has been demonstrated that glutamate and related amino acids bind specifically to sites on synaptic membranes, which exhibit many of the characteristics expected of postsynaptic receptors. Secondly, at higher concentrations (but which may well approximate to those found in the synaptic cleft) these excitatory amino acids stimulate cGMP in accord with their electrophysiological potencies. It would seem prudent therefore when investigating glutamatergic postsynaptic function (and possibly also for aspartate) that each of these parameters should receive due consideration. PMID- 6266223 TI - Biochemical-molecular characteristics of the brain synaptic membrane glutamate receptor. AB - The studies described above have provided evidence for the presence of a high affinity, glutamate binding glycoprotein which has some of the pharmacologic characteristics of the recognition site of neuronal glutamate receptors. In addition, evidence was presented for the distinct molecular nature of this glutamate binding protein as compared to that of the kainic acid binding macromolecule in synaptic membranes and also, for the differential characteristics of the glutamate binding sites as compared to the glutamate transport carriers. Finally, information was presented which is suggestive of the presence and functional integrity of glutamate receptor.ion channel complexes in synaptic membrane preparations. PMID- 6266224 TI - High affinity binding sites for 3H-glutamate in hippocampal membranes: the search for a glutamate receptor. PMID- 6266225 TI - Interaction of depressant and convulsant drugs with the picrotoxinin binding sites in membranes and solubilized forms. PMID- 6266226 TI - GABA and glycine receptors in CNS cultures: autoradiographic binding and electrophysiological studies. AB - Autoradiographic studies have shown that GABA, glycine and their antagonists bicuculline and strychnine are bound to many cultured neurones but not to glial cells. The hyperpolarization of GABA and glycine on CNS neurones is associated with an increase in membrane conductance, whereas the depolarization of glial cells by these amino acids is not accompanied by a change in membrane resistance. Using K+-sensitive electrodes, it was observed that the glial depolarization correlates well with the increase of the extracellular K+-concentration. 4-AP which blocks K+-conductance of excitable cells reversibly abolished both the glial depolarization and the increase of extracellular K+-concentration caused by GABA and glycine. It is concluded that, unlike neurones, glial cells may not possess receptors for GABA and glycine and that the depolarization by these amino acids is an indirect effect caused by an increase of extracellular K+ released from adjacent neurones. PMID- 6266228 TI - Development of excitatory amino acid binding sites in the chick optic tectum. PMID- 6266227 TI - GABA and glycine receptors in rat brain: autoradiographic localization. PMID- 6266229 TI - Some aspects of glycine neurochemistry. PMID- 6266230 TI - THIP, isoguvacine, isoguvacine oxide, and related GABA agonists. PMID- 6266231 TI - Folding of protein fragments. PMID- 6266233 TI - [Analysis of beta-effect on aqueous humor dynamics--distribution and characterization of adenosine 3',5'-monophosphate-dependent protein kinase in anterior segment of bovine eye (author's transl)]. PMID- 6266232 TI - Histamine uptake and metabolism in intact isolated parietal cells. AB - 3H-Histamine binding, uptake and metabolism were investigated in intact isolated and enriched parietal cells from the dog and guinea pig. Histamine uptake was sodium dependent and followed by intracellular metabolism. The only metabolite that was detected and extracted from cytosol has been identified by TLC to N tau methylhistamine. The histamine N-methyltransferase activity appeared to be sodium dependent and was inhibited by mepyramine and chlorpromazine, and also by higher concentrations (10(-4)--10(-3) mol/l) of cimetidine. Two blockers of the sodium channel, amiloride an aminoguanidine, also reduced the enzyme activity by an as yet unknown mechanism. PMID- 6266235 TI - Properties of the "CKp" strain of transmissible gastroenteritis virus. II. Studies on the in vivo viral replication in newborn piglets. PMID- 6266234 TI - [Studies on experimental steroid glaucoma. Report 6. The relation between intraocular pressure and aqueous levels of cAMP in steroid-treated young rabbits' eyes (author's transl)]. PMID- 6266236 TI - The effect of anaerobic corynebacterial immunostimulants on the primary immune response to tetanus toxoid and Perfringens epsilon toxoid. (Short communication). PMID- 6266238 TI - Border disease in Norway. PMID- 6266239 TI - Detection of porcine rotavirus by EM, ELISA and CIET. PMID- 6266237 TI - Storage-related potency changes in monovalent type O1, A5 and C foot-and-mouth disease vaccine preparations. PMID- 6266240 TI - Detection of antibodies against hog cholera virus and bovine viral diarrhea virus in porcine serum. A comparative examination using CF, PLA and NPLA assays. PMID- 6266241 TI - Recanalized umbilical vein due to portal vein occlusion: documentation by sonography. PMID- 6266242 TI - The viral factor in the etiology of acute asthma attacks in children. AB - Over the last decade firm proponents of a viral etiology have risen, alongside those considering mycoplasma as prime agent in the induction of bronchospasm. Since we are not convinced as to the validity of the viral hypothesis, we decided to study a group of asthmatics to detect the different viral antigens serologically, in order to determine which can play a decisive role in the pathogenesis of the asthmatic crisis. Without previous etiologic selection, 37 children admitted as emergency cases with severe asthmatic crises, were chosen for the study. All were being treated as asthmatics and were diagnosed as bacterial or mixed asthmatics according to the Ciba Symposium criteria; the ages ranged from one to eleven years. Four patients presented infections by RS virus and of these, two showed an accompanying infection by Coxsackie B3 and B5. Only one patient presented antibodies against mycoplasma pneumoniae. The incidence of maxillary sinusitis was 75.6%. We found the only 13.5% of the children showed specific antibodies, against any of the 16 viral antigens tested. That is, we find that in parallel with the bacterial infection, there exists a viral infection which is manifested by the increment of specific antibody titers after ten days. The asthmatic symptoms disappeared after antibiotic and corticoid therapy, as opposed to the resistance to this form of treatment reported by McIntosh. PMID- 6266244 TI - Binding of iron by fiber of wheat and maize. AB - Iron II is firmly bound by neutral detergent fiber (NDF) prepared from wheat or maize and NDF accounts for nearly all of the iron binding capability of these cereals. The amount of iron bound depends upon iron concentration, pH, quantity of fiber, and the presence or absence and quantities of inhibitors of binding. Binding is minimal, although appreciable, below pH 4.0, but rises rapidly above pH 5.0 to a maximum near pH 7.0, the limit of stability of iron in the system used. The NDF of wheat binds about 0.38 mg of iron per gram of NDF; that of maize somewhat more than 0.3 mg/g at pH 6.45. Binding of iron by acid detergent fiber (cellulose and lignin) is largely accounted for by its cellulose, and it also is pH dependent but less so than NDF. Iron binding by fiber is strongly inhibited by ascorbic, citric, and phytic acids and by EDTA in low concentrations. Various amino acids produce inhibition, especially cysteine, which inhibits strongly, but others are inactive. Phosphate and calcium are strong inhibitors; taurocholic acid is moderately inhibitory. It appears that a high proportion of ingested nonheme iron combines with fiber of wheat or maize and becomes unavailable for absorption when intake of these cereals are high unless it is released by surges of gastric acid or inhibitors of binding. The promotion of iron absorption by adjuvants such as ascorbic acid, fruit juices, and EDTA may depend in part upon their ability to release iron from its combination with dietary fiber. PMID- 6266243 TI - Nitrate and nitrogen balances in men. AB - Nitrate is a nitrogen-containing compound that is not detected by the traditional Kjeldahl method of nitrogen analysis. Nitrate balance studies were done in order to determine if nitrate production in the human body contributes to the irrationally positive nitrogen balances that have been reported in healthy adults. Seven healthy young men, confined to a metabolic unit, received five diets for 9 days each: a mixed foods diet, a fiber-free egg formula diet, and egg formula with California small white beans, lima beans, and wheat bran added. Nitrate-nitrogen intake with the mixed foods diet was 75 mg/day and nonnitrate nitrogen intake was 19 g/day; crude Kjeldahl nitrogen balance (intake--(urinary + fecal)) was 0.64 +/- 1.23 g/day. Nitrate-nitrogen excretion exceeded intake by 0.10 +/- 0.05 g/day. With the four other diets, nitrate-nitrogen intake was almost nil (about 2 mg/day) and nonnitrate nitrogen intake was 95 mg/kg body weight; crude Kjeldahl nitrogen balances ranged from -0.63 +/- 0.73 to 0.02 +/- 0.45 g N/day. With these four diets, feces contained about 80 mg nitrate nitrogen/day and urine contained about 8 mg. Saliva obtained before lunch had about 1 ppm nitrate-nitrogen with the formula diets and 5 ppm with the mixed foods diet. Net synthesis of nitrate is quite variable but appears to be of the order of 100 mg nitrate-nitrogen/day. Although the excess nitrate excretion increased total nitrogen excretion by less than 5%, it could account for as much as 10 to 20% of unexplained positive nitrogen balances previously reported in well-controlled studies. PMID- 6266245 TI - The role of breakfast in nutrient intake of 5- to 12-year-old children. AB - From 7-day food diaries of a cross-sectional sample of American children (n = 657), breakfast consumption patterns were assessed and related to average daily nutrient intake patterns. Results indicated that few of the children skipped breakfast and that breakfast consumption made a significant contribution to the average child's daily nutrient intake. Further, children who had ready-to-eat cereals at breakfast three or more times during the 1-wk period were found to have consumed significantly less (p less than 0.001) fat and cholesterol and significantly more (p less than 0.001) fiber, thiamin, niacin, riboflavin, iron, folacin, pyridoxine, and vitamins B12, A and D than those who had no ready-to-eat cereal at breakfast. Average total daily intakes of the same groups had fewer significant differences. Comparison of the average nutrient composition of the three types of consumed breakfasts revealed that the average breakfast containing presweetened or nonsweetened ready-to-eat cereal had a higher content of sixteen nutrients and a lower content of five nutrients than did the average breakfast including no ready-to-eat cereal. PMID- 6266246 TI - Dietary fiber or indigestible residue? PMID- 6266247 TI - Fine needle aspiration cytology of uncommon thoracic lesions. AB - Transthoracic fine needle aspiration biopsy provides valuable information influential in patient management, but at the same time it has introduced new interpretative problems. This paper presents some uncommon thoracic lesions, including thymoma, pulmonary hamartoma, pulmonary pseudolymphoma, typical carcinoid tumor, and spindle cell carcinoid mimicking oat cell carcinoma. Each of these cases has unique cytologic features. Since cells derived from these lesions are seen rarely or not at all in exfoliative cytology, lack of familiarity with their cytologic features may result in erroneous interpretation. Other factors contributing to the success of the needle aspiration biopsy are also discussed. PMID- 6266249 TI - Fiber and the gut. PMID- 6266248 TI - Hepatic angiography in a patient with tuberculosis of the liver. AB - The hepatic angiographic features of a 45-year old black woman who was found to have abdominal tuberculosis are described. The clinical and arteriographic findings were similar to those found in malignant disease. A histological diagnosis is essential in such cases. PMID- 6266250 TI - Recovery of adrenal reserve following treatment of disseminated South American blastomycosis. AB - South American blastomycosis commonly involves the adrenal glands as proved in autopsy series, although clinical adrenocortical insufficiency is infrequently suspected. In 1972, an Ecuadorian man was seen with disseminated paracoccidioidomycosis and Addison's disease documented by low basal steroid levels and lack of response to ACTH therapy. The patient has since been treated with a total dose of 4,000 mg of amphotericin B. He discontinued all steroid replacement therapy for two years but remained asymptomatic. Recent evaluation documented improvement in basal steroid production, particularly mineralocorticoids. Adrenal reserve has also been demonstrated by the response of glucocorticoids to ACTH stimulation. This is the first well documented case in which adrenal reserve was recovered following treatment of granulomatous Addison's disease. PMID- 6266252 TI - A study of angiotensin II binding sites in human placenta, chorion, and amnion. AB - The binding of tritiated angiotensin II to 20,000 x g particulate tractions of human placenta, chorion, and amnion was investigated. Binding to particles from the three tissues reached equilibrium within 10 minutes at 29 degrees C and was displaced by the addition of 1,000-fold excess of unlabeled angiotensin II. Scatchard analysis of the data showed that two classes of binding sites were present in the placental preparation. For the high-affinity site, values of 9 x 10(-9) M and 300 fmoles/mg of protein were obtained for the dissociation constant and the binding capacity, respectively. There was little specific binding in chorion and amnion. PMID- 6266251 TI - Pituitary ACTH dependency of nodular adrenal hyperplasia in Cushing's syndrome. Report of two cases and review of the literature. AB - Cushing's syndrome due to nodular adrenal hyperplasia comprises a clinically and biochemically heterogeneous group of disorders whose pathogenesis is unclear. We describe two patients with atypical steroid dynamics and large unilateral adrenal nodules who had pituitary ACTH-dependent disease. In the differential diagnosis of Cushing's syndrome, we recommend repeated ACTH measurement and selective venous sampling-particularly in those patients with impaired dexamethasone suppressibility and abnormal findings on computerized tomography. PMID- 6266253 TI - Improved monitoring of gestational trophoblastic neoplasia using a highly sensitive assay for urinary human chorionic gonadotropin. AB - A radioimmunoassay for urinary human chorionic gonadotropin (hCG) which used antiserum to the hCG beta carboxy-terminal peptide was employed to detect hCG production in women with gestational trophoblastic disease. The urinary hCG assay was considerably more effective in detecting increased hCG production, and, hence, persistent tumor burden, than the commonly used serum hCG beta subunit radioimmunoassay. In two women treated for choriocarcinoma, urinary hCG levels remained distinctly elevated for 2 to 6 weeks, even though the serum hCG level was undetectable; in both cases, the urinary hCG radioimmunoassay reliably predicted the eventual reappearance of hCG in the serum. In six women whose disease remitted, the urinary hCG level declined to the normal range during chemotherapy, and remained there afterward. In eight patients who had been in remission for periods of from 1 to 14 years, urinary hCG levels were in the normal range. We conclude that this highly sensitive and reliable method for the detection of hCG production improves the ability to diagnose persistent trophoblastic disease. PMID- 6266254 TI - Postmenopausal hormone replacement therapy with estrogen periodically supplemented with antiestrogen. AB - To inhibit endometrial stimulation during postmenopausal estrogen therapy, 25 women with climacteric symptoms were treated with a daily dose of 1.25 mg of conjugated estrogens for 7 weeks followed by a period of 10 days with clomiphene citrate administration (50 mg per day). This combination was repeated three times during the 6-month trial. The marked relief of climacteric symptoms with estrogen was slightly less during clomiphene treatment. Uterine bleeding occurred five times during estrogen treatment periods but never during or after clomiphene supplementation. Histologic examination revealed endometrial atrophy in 41% of the samples after the first estrogen treatment, whereas after the first and third clomiphene periods this was increased to 77% and 73%, respectively. The first clomiphene treatment significantly decreased the concentrations of cytosol estrogen and progestin receptors in endometrium, as compared with the levels recorded at the end of the preceding estrogen therapy. The depression in the cytosol estrogen receptor concentration was persistent, whereas cytosol progestin receptor concentration tended to increase during the subsequent estrogen-plus clomiphene treatment. Estrogen declined serum concentration of follicle stimulating hormone (FSH), whereas the concentration of luteinizing hormone (LH) and prolactin remained unchanged. Clomiphene did not change the levels of these hormones from those observed during the estrogen treatment. The concentration of free fatty acids in serum was increased during the estrogen and clomiphene treatments, whereas the levels of cholesterol and high-density lipoprotein- cholesterol did not change. Our results suggest that this treatment regimen relieves climacteric symptoms without endometrial stimulation or other adverse effects. Thus, clomiphene appears to be a practical alternative to progestin for interruption of the postmenopausal endometrial effect of estrogen. PMID- 6266255 TI - Paget's disease of the vulva with extension into the urethra, bladder, and ureters: a case report. PMID- 6266256 TI - Angiomatoid malignant fibrous histiocytoma of the orbit. PMID- 6266258 TI - Immune stimulation, inflammation, and changes in hematopoiesis. Host responses of the murine spleen to infection with cytomegalovirus. AB - Spleens from C3D2F1 mice acutely infected with murine cytomegalovirus (MCMV) were examined for mechanisms of viral clearance and alteration of immune function. Inclusion-bearing cells in the perifollicular marginal zone were found to peak at Day 3 after infection and to be associated with infiltrates of polymorphonuclear leukocytes (PMNs). Inclusions and PMNs were cleared by Day 6. Hematopoietic islands, although not impinged upon, could not be found by Day 3 after infection but reappeared and were considerably enlarged by Day 6. Most importantly the T dependent areas of the spleens revealed no viral inclusions and no lysis. Stimulated morphology was seen in T-dependent areas by Day 1 after infection and remained so for over 3 weeks. T-independent areas contained germinal centers at Day 4 and thereafter. Therefore, in the absence of viral cytopathologic features in the T-dependent and T-independent areas, other mechanisms must account for the immunosuppression observed during acute infection. The observations of an activated morphology are compatible with other data demonstrating an alteration in immunoregulation as the mechanism for the immunosuppression associated with MCMV infection. PMID- 6266257 TI - Short-term effects of vitamin D3 and 1,25-dihydroxyvitamin D3 on osteomalacia in uremic rats fed a low calcium-low-phosphorus diet. AB - The objectives of this study were to evaluate the effects of vitamin D(3) (D(3)) and 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) on uremic bone disease independent of their action on the intestine. The histomorphology of tibial metaphyses in uremic (5/6 nephrectomized [5/6 Nx]) rats fed a low-calcium-low phosphorus (LCLP) diet was compared with sham-operated (SO) rats fed an LCLP diet and 5/6 Nx rats fed an LCLP diet and given 15,000 IU D(3) or 5 units (135 ng) 1,25-(OH)(2)D(3) daily for 7 days. A marked osteomalacia characterized by an increased percentage of active and inactive trabecular osteoid surface and thickened growth plates developed in proximal tibial metaphyses in 5/6 Nx rats given the placebo, compared with SO rats. These bone changes were associated with relative hypophosphatemia, hypophosphaturia, and hypercalciuria in 5/6 Nx rats. In 5/6 Nx rats treated with D(3) or 1,25-(OH)(2)D(3) the growth plates had undergone mineralization and vascular invasion and were markedly reduced in thickness. Other parameters of osteomalacia in trabecular bone were not different from 5/6 Nx rats given the placebo. There was a significant decrease in osteoclasts per millimeter of trabecular surface perimeter in D(3)- and 1,25 (OH)(2)D(3)-treated rats. These bone changes were associated with hypercalcemia, hyperphosphatemia, and hyperphosphaturia, compared with 5/6 Nx rats given the placebo. It was concluded that in uremic rats fed the LCLP diet, shortterm treatment with either pharmacologic levels of D(3) or 1,25-(OH)(2)D(3) corrected only lesions in the growth plate. Osteoid seams were not reduced in treated rats, although the serum calcium-phosphorus product was elevated. The 5/6 Nx rat fed the LCLP diet appears to be a useful model for the rapid induction of uremic osteomalacia in adult animals. PMID- 6266260 TI - Effects of an ACTH short chain neuropeptide in man. AB - The authors studied the effect of an ACTH 4-9 analogue (the shortest behaviorally active fragment of the ACTH neuropeptide) on mood in normal aging volunteers. These mood changes, described as a sense of well-being, energy, and drive, are consistent with an arousal-stimulant mechanism of action of the compound. No effect of the compound was found on attention or memory. Because of its apparent safety and the lack of adverse effects, the authors suggest that this short chain neuropeptide be further explored in older individuals for its mood-elevating and potential antidepressant properties. PMID- 6266261 TI - Activity of imidazoles against Leishmania tropica in human macrophage cultures. AB - The anti-leishmanial activity of four imidazoles has been determined in Leishmania tropica-infected human monocyte-derived macrophage cultures. One of the imidazoles, hydrolyzed ketoconazole [cis-1-[4-[2-(2,4-dichlorophenyl)-2-(1H imidazol-1-ylmethyl)-1,3-dioxolan-4-yl] methoxyphenyl]piperazine], eliminated 80 and 95% of the parasites at drug concentrations (2.0 and 2.5 microgram/ml) that are achievable in vivo by a structurally similar compound, ketoconazole. These results demonstrate that an imidazole has anti-leishmanial activity in a model system, and suggests that hydrolyzed ketoconazole should be considered for in vivo trials in animal models of the disease. PMID- 6266259 TI - The effects of naloxone in chronic schizophrenia. AB - In a placebo-controlled, double-blind crossover study of 14 male chronic schizophrenic patients, high doses of the opiate antagonist naloxone were given intravenously. Hallucinations measured on a verbal-report scale were significantly decreased after naloxone administration. The authors suggest that this apparent action of naloxone is mediated by central opiate receptors and that it may result from an interaction between central endorphin systems and central catecholaminergic neurons. PMID- 6266262 TI - Developmental disorders of the fetus in some arthropod-borne virus infections. AB - A number of arboviruses have been associated with congenital defects in domestic aminals and man. In this review comparison is made of the temporal association between epidemics of arboviruses affecting man and animals in which there is an obvious relationship between the infection and the fetal defects, and arboviruses which cause no overt clinical symptoms in the vertebrate host but result in deformities of the fetus. The danger to the fetus following the use of live attenuated virus vaccines against several important arbovirus diseases is also examined. It is concluded that arboviruses which are capable of infecting humans or animals without producing overt clinical signs, and attenuated vaccine viruses pose the greatest threat to the fetus. PMID- 6266263 TI - An outbreak of Mayaro virus disease in Belterra, Brazil. I. Clinical and virological findings. AB - An outbreak of human illness caused by Mayaro (MAY) virus occurred in Belterra, Para, Brazil in the first half of 1978. A total of 55 cases were confirmed, 43 by virus isolation and serology, and 12 by serology alone. The disease in Belterra presented as a distinct clinical syndrome characterized by fever, arthralgia and exanthema. No fatalities could be attributed to MAY virus infection. Arthralgia, accompanied by joint edema in 20% of cases, was a very prominent sign which caused temporary incapacity in many patients. Arthralgia was present in virtually all confirmed cases and persisted in some for at least 2 months, although with decreasing severity. Rash was present in two-thirds of the cases, and was either maculopapular or micropapular. The incidence of rash was higher in children than in adults. Contrary to arthralgia, which started with the onset of clinical illness, rash usually appeared on the 5th day and faded within 3-4 days. Fever, chills, headache, myalgia, lymph-adenopathy and other minor clinical manifestations were also recorded, and generally persisted for from 2-5 days. Leucopenia was a constant finding in all cases. Mild albuminuria was seen in four of 25 patients, and slight thrombocytopenia was seen in 10 of 20 cases. The fact that viremia levels higher tha 5.0 log10/1.0 ml of blood were recorded in 10 patients rises the possibility that man may have be an amplifying host in the MAY virus cycle. The MAY virus illness, as seen in Belterra, has clinical features similar to those observed in persons infected with chikungunya virus. PMID- 6266265 TI - An outbreak of Mayaro virus disease in Belterra, Brazil. III. Entomological and ecological studies. AB - Results in entomological and vertebrate host investigations made during dual outbreaks of Mayaro (MAY) and yellow fever (YF) viruses in Belterra, Para, Brazil in 1978 are reported. Over 9,000 insects representing 26 species were assayed in 396 pools for the presence of arboviruses. Pools of Haemagogus janthinomys Dyar yielded the only isolates of either MAY or YF virus. The minimum field infection rate for nine isolates of MAY virus from Hg. janthinomys was 1:82, and for two isolates of YF virus was 1:368. Analysis of collection data showed Hg. janthinomys to be attracted to man as a blood source and present in all habitats sampled, although most abundant in the forest canopy. Twelve hundred bird sera and 584 mammal sera were tested by hemagglutination-inhibition (HI) tests for antibody to MAY virus. Highest MAY antibody prevalence rates were found among marmosets (Calithrix argentata, 32 positive of 119 tested, 27%). Mayaro virus was also isolated from the blood of a sylvan marmoset captured at the peak of the MAY virus outbreak. Experimental infection of marmosets with MAY virus confirmed that a substantial viremia follows infection with this virus. Marmosets were also found with HI antibody to YF virus (5/119, 4%). The results presented indicate that Hg. janthinomys was the principal vector of both MAY and YF viruses and that marmosets were the main amplifying hosts for MAY virus, and perhaps for YF virus as well. PMID- 6266264 TI - An outbreak of Mayaro virus disease in Belterra, Brazil. II. Epidemiology. AB - Epidemiological investigations of an outbreak of Mayaro (MAY) virus which occurred inthe rural village of Belterra, Para, Brazil are reported. Human cases were first recorded in December 1977 and continued through June 1978. Approximately 20% of the more than 4,000 persons resident in Belterra were infected, and a very high proportion of those infected suffered overt clinical illness. Cases were identified in all areas of Belterra and among all age groups; however, the greatest number of cases was seen among those who resided in close proximity to the forests. Yellow fever (YF) virus was also active in Belterra concurrently with the MAY virus outbreak. Six human cases of YF were identified, of which five were fatal. The YF outbreak ended following YF vaccination of the human population. PMID- 6266266 TI - Transovarial transmission of St. Louis encephalitis virus by Culex pipiens complex mosquitoes. AB - Experiments were conducted to determine whether transovarial transmission (TOT) of St. Louis encephalitis (SLE) virus occurs in Culex pipiens complex mosquitoes, the principal vectors of SLE virus in the central-eastern United States. In 1978, field-collected mosquitoes from Memphis, Tennessee, and McLeansboro, Illinois, were used; during 1979, colonized mosquitoes from Chicago, Illinois, and Memphis, Tennessee, were used. Mosquitoes were infected by feeding on viremic chicks inoculated with an SLE virus strain isolated from Cx. pipiens complex mosquitoes collected from Memphis, Tennessee, in 1976. During the 1979 experiments, progeny larval and adult mosquitoes were held at two temperatures, 18 and 25 degrees C. Progeny were tested for virus by plaque assay in duck embryo cell cultures and by inoculation of Aedes albopictus C6/36 cells and examination by immunofluorescence. In 1978, most of the progeny tested were from the first ovarian cycle, and a single occurrence of TOT was documented. In 1979, a single TOT occurred from 46,856 first ovarian cycle progeny, whereas 7 of 9,234 progeny of the second ovarian cycle were infected. The rate of TOT was higher for progeny of Memphis than Chicago mosquitoes, and for mosquitoes held at 18 degrees C than at 25 degrees C; however, these differences were not statistically significant. Four positive pools were females, and three were fed on chicks for transmission attempts. The positive Chicago mosquito pool failed to transmit, but both Memphis pools successfully transmitted virus. The overall rates of TOT of SLE virus in progeny of the first and second ovarian cycle were, respectively, 1/45, 151 and 1/1,460. The significance of these results as they relate to the natural history of SLE virus is discussed. PMID- 6266267 TI - Growth inhibition of axenic Entamoeba histolytica by tubercidin and ara-A. AB - Several analogs of nucleic acid components including 7-deazaadenosine (tubercidin), adenine 9-beta-D-arabinofuranoside (ara-A), 8-azaguanine, 6 azathymine, 6-mercaptopurine, 6-mercaptopurine arabinoside, 6-mercaptopurine riboside and 1,3-dideazapurine (benzimidazole) were tested for inhibition of growth of an axenic strain of Entamoeba histolytica in 72 hour experiments. Metronidazole and emetine were included in the experiments for comparison. Tubercidin and ara-A, analogs of adenosine, were the most potent of the tested growth inhibitors with amebistatic concentrations of about 0.6 and 3.0 microM, respectively. The other analogs did not significantly inhibit amebal growth below 100 microM. In the present study metronidazole and emetine had amebistatic concentrations, respectively, 17- and 60-fold higher than tubercidin. PMID- 6266268 TI - Islet autotransplantation after pancreatectomy for chronic pancreatitis with a new method of islet preparation. AB - Near-total (95 percent) pancreatectomy with intraportal islet autotransplantation was performed in five patients with chronic pancreatitis. Two patients are completely insulin-independent 7 and 14 months after autotransplantation; the other three patients obtained partial independence. A new method of islet cell preparation is described. Islet cell autotransplantation after total or near total pancreatectomy should at present be viewed with cautious optimism. Additional cases need to be studied and followed up before its role in the surgery of chronic pancreatitis will be clear. PMID- 6266269 TI - Apparent brain atrophy and subdural hematoma following ACTH therapy. AB - A case of subdural hematoma following ACTH-Z therapy for infantile spasms was presented. A female baby of 5 months old showed little clinical evidence of cerebral dysfunction associated with subdural hematoma. There have been several reports about the relationship between steroid treatment and apparent brain atrophy on the CT brain scans. Then, we studied the CT brain scans before and after ACTH-Z therapy for infantile spasms, atonic seizure or Lennox syndrome and showed some relationship between apparent brain atrophy on the CT brain scans and ACTH-Z treatment. We also discussed the possible etiology of apparent brain atrophy and subdural hematoma, and stressed the necessity of extreme caution with long-term ACTH-Z administration. PMID- 6266271 TI - An acute variant of subacute sclerosing panencephalitis: an autopsy case report. AB - An acute variant of subacute sclerosing panencephalitis (SSPE) was described in a 5-year-old boy who showed rapid progression of coma within 14 days of right hemiplegia. He had measles at 3 years of age. The diagnosis of SSPE was based on the following findings: high anti-measles antibody titer in the serum and in the spinal fluid, periodic complex of EEG, and typical pathological changes of the brain. Treatment with transfer factor failed to improve the worsening clinical course. It is suggested that SSPE should be considered in the differential diagnosis of acute fulminating encephalitides or intracranial vascular lesions. PMID- 6266270 TI - Influence of ACTH therapy on overnight sleep polygrams in infantile spasms. AB - Overnight sleep polygrams were recorded before and during therapy in nine patients with infantile spasms. Results showed that ACTH therapy increased the waking time and decreased rapid eye movement sleep. Thus it caused sleep disturbance in patients with infantile spasms. During ACTH therapy the number of rapid eye movements/min and the pulse rate decreased significantly. Body movements/min also decreased, but not significantly. These results suggest that ACTH therapy may inhibit functions of the central nervous system. The respiratory rate increased during ACTH and clonazepam therapy, probably in association with the decrease or the absence of seizures. These findings indicate the necessity for further studies on whether ACTH therapy is really of value in patients with infantile spasms, and show that if ACTH is given, the period of therapy should be as short as possible. PMID- 6266272 TI - Eyelid tumors of sweat gland origin. AB - Tumors of sweat gland origin are not uncommon in the periocular region. These tumors frequently pose diagnostic difficulty due to the wide range of histopathological patterns, and to the fact that they may be infiltrative or have metastatic potential despite their relatively benign appearance. This report discusses the classification and diagnosis of five sweat gland tumors with variable histological appearance, including syringoma, mixed tumors, adenoma of ductal origin, and mucinous adenocarcinoma of sweat gland origin. PMID- 6266273 TI - Malignant mixed tumor of the lacrimal gland. A clinicopathologic report of two unusual cases. AB - Two cases of malignant transformation in an originally benign mixed tumor of the lacrimal gland (pleomorphic adenoma) are presented. In both patients the unusual histopathologic appearance of the malignant component gave rise to considerable problems in clinical and histopathologic diagnosis. In one case of the malignant tumor had a sarcomatous appearance, while in the other there was sebaceous differentiation mimicking an adenocarcinoma of the Meibomian glands. PMID- 6266274 TI - Cells accumulating 3h-glycine in the goldfish retina. AB - Glycine accumulating neurons occur among amacrine cells of the goldfish retina with processes distributed in the inner plexiform layer. Similar cells also occur, although much more rarely, among the horizontal cells and in the outer plexiform layer. The latter cells are readily observable only after heavy labelling. They may emit processes ending close to the photoreceptor terminals. PMID- 6266275 TI - Effects of thermal load on ion release of the rabbit vitreous body. AB - Ion-release of the rabbit vitreous body through a dialysis membrane against water was studied. To evaluate one of thermal changes in the vitreous properties, the vitreous was heated or cooled before dialysis. The average wet weight of the normal vitreous was 1.61 +/- 0.20 g and dry to wet weight ratio was 1.33 +/- 0.04%. The dry weight, sodium, potassium, and chloride concentrations of the vitreous were decreased as an exponential function curve by dialysis. A decreasing ratio was prominent in the heated vitreous, the frozen vitreous and the non-thermo-treated (control) vitreous in turn. Calcium and magnesium release from the rabbit vitreous body was slow and differences among the heated, frozen and non-thermo-treated vitreous bodies were not significant, suggesting some different capture-mechanisms between the monovalent and bivalent ions. PMID- 6266276 TI - Purification and characterization of the gag gene products of avian-type C retroviruses by high-pressure liquid chromatography. PMID- 6266277 TI - Rapid analysis of modified tRNAphe from yeast by high-performance liquid chromatography: chromatography of oligonucleotides after RNase T1 digestion on aminopropylsilica and assignment of the fragments based on nucleoside analysis by chromatography on C18-silica. PMID- 6266278 TI - "Western blotting": electrophoretic transfer of proteins from sodium dodecyl sulfate--polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A. PMID- 6266279 TI - A reliable method for the recovery of DNA fragments from agarose and acrylamide gels. PMID- 6266280 TI - The pentaammineruthenium(III)histidine complex in ribonuclease A: application to the assignment of histidine proton resonances. PMID- 6266281 TI - Cellular composition of the rostral pars distalis of the anterior pituitary gland of the alewife, Alosa pseudoharengus, during the spawning run. AB - The rostral pars distalis of the anterior pituitary gland of the marine alewife, Alosa pseudoharengus, during its annual spawning run to fresh water was examined histologically. The rostral pars distalis is composed of many interconnecting follicles of various sizes. Contrary to earlier reports, the follicular epithelium contains not only prolactin (PRL) cells but corticotropic (ACTH) cell and thyrotropic (TSH) cells (in addition to two nonendocrine cell types). Basally all three endocrine cell types make direct contact with the basement membrane which separates the follicles from the neurohypophysial processes. Apically, however, only the prolactin cells, the largest of the three, protrude into the follicular lumen by means of the small ciliated apical protruberance. All other cellular elements are sealed from the follicular lumen by a layer of covering cells which have properties of transitional epithelial cells. In the follicular epithelium, the slender TSH cells are intercalated between the large conspicuous prolactin cells. The ACTH cells, the smallest of the three endocrine cells, lie in deep invaginations in the basal regions of the individual PRL cells in such a way that on cursory examination they can be mistaken for the nuclei of the latter. Only a small portion of the cellular surface of the ACTH cell escapes the enveloping prolactin cell to make contact with the basement membrane of the follicle. In teleosts, prolactin, ACTH, and TSH have all been implicated in the regulation of hydromineral metabolism and reproductive development. The intimate spatial relation between the three endocrine cells in the alewife rostral pars distalis thus raises the possibility of some functional interactions at the adenohypophysial level, perhaps as an adaptation of this anadromous teleost whose reproductive development and behavior is associated with large changes in ambient salinity. The functional significance of the follicular lumen is discussed together with possible sensory functions of the PRL cells. PMID- 6266282 TI - Ultrastructure of human spermatozoa in the presence of the spermicide nonoxinol-9 and a vaginal contraceptive containing nonoxinol-9. AB - The effect of nonoxinol-9, a potent non-ionic, surface-active spermicide and of the vaginal contraceptive Patentex oval containing this spermicide, on human sperm ultrastructure were studied by transmission electron microscopy. Pooled human semen was mixed either with nonoxinol-9 to give a final concentration of 1.25 or 0.05% or with Patentex oval (final concentration of the spermicide nonoxinol-9 1.25%). Saline containing no spermicidal agent served as control. After incubation at 37 degrees C for 10 min., the washed sperm pellet was processed for electron microscopy. Human spermatozoa from control experiments showed a normal ultrastructure whereas significant changes occurred after the addition of nonoxinol-9 or Patentex oval to human semen. The plasma membrane and the acrosomal membrane complex were removed. The nuclear membrane was swollen, showed breaks, discontinuities and an enlarged submembranous space. Different stages of nuclear chromatin decondensation were observed. In the middle piece, the bi-laminar membrane of the mitochondria appeared as a mono-layer membrane. The normal cristae were destroyed, the mitochondriae were empty or contained fine granular material. The observed irreversible severe membrane alterations cause an immediate devitalization of the spermatozoa and support the effectiveness of the spermicide nonoxinol-9 and the vaginal contraceptive Patentex oval. PMID- 6266283 TI - Aminophylline. PMID- 6266284 TI - Antibiotics and neuromuscular function. PMID- 6266285 TI - Seasonal variations of serum IgE levels in normal children. AB - The importance of season as a variable in total IgE production in normal children is demonstrated. Recent history of allergen exposure as well as respiratory infection, both of which are seasonally determined, should be considered in evaluating serum IgE values. PMID- 6266286 TI - Atypical lymphocytosis in children. AB - A complete blood count performed during the evaluation of a febrile or traumatized child may show the presence of atypical lymphocytosis. Although atypical lymphocytes occur in several conditions, they are most closely associated with infectious mononucleosis (IM). We initiated a study to determine if the presence in children of atypical lymphocytosis without the triad of splenomegaly, pharyngitis, and adenopathy is a manifestation of IM. Heterophil antibody (HA) and Epstein-Barr virus (EBV) titers were performed on 45 children with greater than or equal to 5% atypical lymphocytes. None had a significant HA titer. Thirty-three were seronegative for EBV, and 11 had titers indicative of past infection. One child had an antibody pattern suggesting a recent EBV infection; none had a titer consistent with acute IM. We conclude that isolated atypical lymphocytes does not point to infectious mononucleosis. PMID- 6266287 TI - Toxicosis in sows and their pigs caused by feeding rations containing polybrominated biphenyls to sows during pregnancy and lactation. AB - The toxicity and the distribution of polybrominated biphenyls (PBB) were investigated by feeding rations containing different concentrations of PBB to sows during pregnancy and lactation. Sows and newborn pigs were clinically unaffected. Mortality was increased among pigs nursing sows fed rations containing PBB. Although transplacental passage of PBB resulted in an appreciable amount of PBB in tissues of newborn pigs, far more PBB were transferred to the pigs through the milk. On a body-weight basis, nursing pigs consumed PBB in concentrations similar to the concentrations given to the sows. The highest tissue concentrations of PBB (fat basis) were found in the liver, followed by the adipose tissue, kidney, and brain. Dietary concentrations of 10 mg of PBB/kg of feed increased serum concentrations of alkaline phosphatase, alanine aminotransferase, and thyroid hormones of pigs, whereas dietary concentrations of 100 or 200 mg of PBB/kg of feed caused those values to decrease. Gross pathologic changes consisted of increased weight of the thyroid gland of newborn pigs and increased weight of the liver of 4-week-old pigs. Histologically, thyroid glands of newborn pigs were slightly hyperplastic, and the colloid was scant and vacuolated. In the liver, lesions consisted of fatty change and centrolobular necrosis; changes were more severe in the sows than in the pigs nursing those sows. Measuring serum concentrations of ornithine carbamoyltransferase was the most effective clinical test in assessing the degree of liver damage in the pigs. PMID- 6266288 TI - Effects of bovine viral diarrhea virus infection on bovine polymorphonuclear leukocyte function. AB - Four procedures were used to evaluate the function of polymorphonuclear leukocytes (PMN) isolated from the blood of cattle experimentally infected with bovine viral diarrhea (BVD) virus: (1) uptake of am emulsion of paraffin oil and Escherichia coli lipopolysaccharide, (2) nitroblue tetrazolium reduction, (3) chemiluminescence, and (4) iodination, or the conversion of iodide to a trichloroacetic acid-precipitable form. A marked impairment of iodination was consistently observed after infection with either a cytopathogenic or a noncytopathogenic strain of BVD virus. A corresponding decrease in paraffin oil uptake, nitroblue tetrazolium reduction, and chemiluminescence was not observed. Serum from BVD virus-infected animals did not depress iodination by normal control PMN in vitro. The iodination, procedure evaluates the activity of the myeloperoxidase, hydrogen peroxide, halide system. This system has potent bactericidal, fungicidal, and virucidal effects. The data indicate that oxidative metabolism by PMN from BVD virus-infected cattle is normal, but that the myeloperoxidase, hydrogen peroxide, halide antibacterial system is impaired. This could be explained by an inhibition of degranulation in PMN from infected cattle. The observed defect in iodination by PMN after BVD virus infection was compounded by a decrease in the number of circulating PMN. The impairment of PMN function may partially explain the increased susceptibility of cattle to secondary bacterial infection during infection with BVD virus. PMID- 6266289 TI - Canine parainfluenza-Bordetella bronchiseptica vaccine immunogenicity. AB - The immunogenicity and safety of 3 serials of a canine parainfluenza (CPI) virus Bordetella bronchiseptica vaccine was evaluated. Each serial was used to vaccinate 10 dogs with single doses given intranasally. The 30 vaccinated and 10 nonvaccinated controls dogs were challenge exposed with aerosols of virulent CPI virus and B bronchiseptica at 18 days and at 21 days, respectively, after vaccination. After challenge exposure, none of the 30 vaccinated dogs had clinical signs of disease; however, 9 of the 10 nonvaccinated dogs developed coughing problems. The CPI virus was isolated from nasal swab specimens obtained from nonvaccinated dogs on an average of 5.1 days after challenge exposure, but was not isolated from any of the specimens obtained from the vaccinated dogs. Bordetella bronchiseptica was isolated from nasal swab specimens obtained from both vaccinated and nonvaccinated dogs up to 18 days after challenge exposure. The erythrocyte sedimentation rates and total leukocyte counts for control dogs were generally increased, in contrast to those for the vaccinated groups. Dogs showed a primary serologic response to CPI virus and B bronchiseptica after vaccination and an anamnestic response to the bacterium after challenge exposure. Adverse local or systemic reactions attributable to the bivalent vaccine were not observed in the vaccinated dogs. PMID- 6266290 TI - Induction of persistent infection in mice and oncogenic transformation of mouse macrophages with infectious bovine rhinotracheitis virus. AB - Infectious bovine rhinotracheitis virus (IBRV) established long-term persistent infection in intracerebrally inoculated athymic nude mice. After intraperitoneal injection into outbred mice, virus was isolated for only 3 days from spleens and livers. In vitro inoculation of outbred mouse spleen fragments with IBRV resulted in persistent infection and subsequent transformation of spleen macrophages. The IBRV-specific membrane and intracellular antigens were detected by indirect immunofluorescence techniques in transformed cells in early in vitro passages. The presence of IBRV genetic formation was confirmed by in situ hybridization. The IBRV-transformed mouse macrophages induced fibrosarcomas and cystic tumors in athymic nude mice. Infective virus could not be rescued from transformed cells by cocultivation with rabbit kidney cells, treatment with iododeoxyuridine, or ultraviolet irradiation. PMID- 6266291 TI - Lyophilized hyperimmune equine serum as a source of antibodies for neonatal foals. AB - In a study with 15 neonatal foals (5 per treatment group), foals were fed within 4 hours of birth as follows: 250 ml of colostrum, 250 ml of lyophilized serum reconstituted at 5 times the original concentration, or 250 ml of a mixture (1:1) of colostrum and lyophilized serum. Foal serum samples were tested for immunoglobulin (Ig)G concentration and titrated for anti-equine rhinovirus 1 and anti-equine influenza A1 and A2 antibodies at 0 and 24 hours after foals were born. Except in a foal which had suckled the dam before treatment, there was no evidence of IgG or specific viral antibodies in the samples taken at birth. There were no significant differences found in the serum IgG concentrations and antibody titers among the 3 treatment groups. Seemingly, IgG was absorbed efficiently from both serum and colostrum, so that the use of reconstituted lyophilized serum as a prophylactic measure of conferring passive immunity to a newborn foal deserves serious consideration. PMID- 6266292 TI - Localization of foot-and-mouth disease viral antigens in mammary gland of infected cows. AB - Virolactias as a result of foot-and-mouth disease infection in dairy cattle would indicate active virus replication in the bovine mammary gland. In the present study, virus was readily detected throughout the mammary gland by infectivity assay after cows were exposed to the virus either by aerosol or by a combination of intramammary-IV inoculation. Furthermore, immunofluorescent and hematoxylin and eosin staining of alternate frozen sections showed viral antigens in rounded alveolar cells with pyknotic nuclei. PMID- 6266293 TI - Adrenocortical suppression in the dog after a single dose of methylprednisolone acetate. AB - Adrenal function was assessed in dogs after intramuscular administration of a single dose of methylprednisolone acetate (MPA). Twelve dogs were test challenged with adrenocorticotropic hormone (ACTH) and then assigned randomly to 1 of 3 groups and given MPA. Individual groups were test challenged with ACTH 2, 3, or 4 weeks later. All dogs were rechallenged 5 weeks after MPA administration. Plasma cortisol concentration was determined by radioimmunoassay. Basal plasma cortisol (time 0) was depressed on weeks 2 and 3, but not on weeks 4 and 5. Adrenal response to ACTH (increment of cortisol change) was suppressed on weeks 2, 4, and 5, but not on week 3. It was concluded that a single dose of MPA is capable of altering adrenal cortical function in dogs for at least 5 weeks. PMID- 6266295 TI - Isolation of a rotavirus from a newborn dog with diarrhea. AB - A rotavirus was isolated from a newborn dog that died after having clinical signs of diarrhea. Virus particles with rotaviral morphologic features were observed by transmission electron microscopy in the intestinal homogenate collected at necropsy. Cytopathic effects were observed, and rotaviral antigens were detected by indirect immunofluorescence in MA-104 monolayer cultures (a fetal rhesus macaque kidney cell) inoculated with intestinal homogenate. This rotavirus isolate, designated LSU 79C-36, may be a specific canine rotavirus or a rotavirus from another species. PMID- 6266294 TI - Evaluation of chemical disinfectants for aleutian disease virus of mink. AB - Nine chemicals and commercial disinfectants were tested for inactivation of Aleutian disease virus of mink. In the presence of distilled water, a commercial disinfectant (O-Syl), halogen derivatives (iodophor and sodium hypochlorite), and glutaraldehyde (2.0%) inactivated 4 log10 (based on 0.25 ml) of the virus within 10 minutes at 23 C. Formalin (2.0%) and O-Syl were slower to inactivate the virus, but achieved a 4 log10 reduction in titer by 30 minutes' contact time. In the presence of 10% bovine serum, formalin (1.0%), O-Syl, and sodium hydroxide (0.5%) achieved a 4 log10 reduction within 10 minutes. All agents tested had some virucidal effect. PMID- 6266296 TI - Epizootiologic study of bluetongue: virologic and serologic results. AB - Heparinized blood and serum samples were obtained from 1,295 ruminants in herds or flocks with bluetongue virus (BTV) infection in 4 western states. Submissions were from herds or flocks with clinical bluetongue (BT), as well as from animals on premises with no history of BT disease. Insects, including Culicoides variipennis, were collected in areas enzootic for BT disease. Viral isolations were in 10-day-old embryonating chicken eggs that were then adapted to Vero cells for serotyping. Sera were tested from group-specific antibody to BTV by the micro agar gel precipitin (AGP) test. Viral isolations were from cattle (81), sheep (122), goats (9), antelope (2), and C varipennis (5). There were 7 isolates of serotype 120, 114 of serotype 11, 42 of serotype 13, and 56 of serotype 17. In herds or flocks from which BTV was isolated, 51% of cattle, 56% of sheep, 21% of goats, and 52% of antelope had AGP antibodies. Virus was isolated from 43% of the cattle and 23% of the sheep that had no demonstrable evidence of AGP antibodies. Viral isolations were seasonal, occurring from August until December. Approximately 30% of the herds or flocks from which virus was isolated had more than one serotype of virus causing infection. PMID- 6266297 TI - Survival among patients with lung cancer. An epidemiologic study. AB - A series of 446 patients with lung cancer, comprising all cases diagnosed in a defined population of approximately 300,000 persons during a period of 4 yr, were studied prospectively and followed for 5 yr or until death. Histologic or cytologic confirmation of the diagnosis was achieved in 431 cases (97%). Only 140 patients (31%) were alive 1 yr after diagnosis, and only 19 patients (4%) were alive after 5 yr, with no significant difference between the men and women. The 5 yr. survival rates among patients with epidermoid. small-cell anaplastic, and adenocarcinoma were 6, 2, and 4%, respectively. The patients could also be divided into prognostically meaningful groups according to the symptomatic staging proposed by Feinstein. Of the 427 patients who had died within 5 yr, 410 (96%) had died of lung cancer and only 17 (4%) had died of other diseases. PMID- 6266298 TI - Disseminated blastomycosis and coccicioidomycosis in the same patient. PMID- 6266299 TI - Angiotensin converting enzyme concentrations in the lung lavage of normal rabbits and rabbits treated with nitrogen mustard exposed to hyperoxia. AB - Increased concentrations of angiotensin converting enzyme (ACE) were found in lung lavages from rabbits exposed to hyperoxia for 72 h and the concentrations of ACE were correlated with ratios of extravascular lung water to body weight (r = 0.69, p less than 0.05) and albumin concentrations in lung lavages (r = 0.89, p less than 0.01). In parallel studies, rabbits treated with nitrogen mustard in which granulocytopenia was maintained throughout the 72-h hyperoxic exposure period had less evidence of edematous lung injury and lower concentrations of ACE in their lung lavages than similarly treated rabbits in which granulocytopenia was not maintained. The results suggested that granulocytes contribute to acute edematous lung injury from hyperoxia and that ACE concentrations in lung lavages reflect this process. PMID- 6266300 TI - Diagnosis of histiocytosis X. PMID- 6266301 TI - [Plasma cortisol response after stimulation with ACTH in postmature newborns (author's transl)]. AB - Authors have studied, in three series of newborns-I) normal term: II) small for date, and III) postmature-, the basal levels of plasmatic cortisol and after stimulation with ACTH. Blood samples were obtained at the 48 hours and 10 days of life, respectively. There are not significative differences in the three groups neither in the basal levels of plasmatic cortisol nor after stimulation (p greater than 0.05). These results show no correlation between postmaturity and fetal adrenal primary or secondary hypocorticism. PMID- 6266302 TI - [Effect of chronic administration of cimetidine on adenohypophysis secretion in children]. AB - In view of the existing disagreement on the hormonal effects of a chronic treatment with cimetidine, we have studied on a sample of 18 children, the possible alterations that might occur. A comparison has been established between basal conditions and a two-month treatment with 500 mg. a day, on levels of GH, PRL, LH, FSH, TSH and cortisol (as an indirect measurement of ACTH). The statistic study has not shown any noticeable difference in the considered period of time, and dose that has been used does not provoke any alteration in adenohypophyseal secretion. PMID- 6266303 TI - Flow cytometry and cytomorphology in primary resectable breast cancer. AB - Using flow cytometry for DNA analysis, ploidy and proliferative activity were measured in 43 cases of primary resectable breast cancer, 24 of which were also assayed for estrogen receptors. Tumors were studied histopathologically by multiple samples and cytopathologically by means of imprint smears and pepsinized cell suspensions. Cytologic preservation was far superior in imprint smears than in cell suspensions or histologic sections. As determined by the DNA index (tumor G1/G0:normal G1/G0), 72% of the tumors were aneuploid, with the majority falling between diploid and tetraploid. There was no correlation of ploidy with tumor cell proliferation expressed as percentages in the S-phase. A high percentage of S-phase cells was associated with estrogen receptor negativity and tended to correlate with cytologic atypia but showed no correlation with UICC stage, menopausal status, tumor size, lymph node involvement or histologic degree of malignancy. In contrast, ploidy showed no correlation with any of the above parameters but served as a reliable marker for individual tumors since it did not change with time in multiple biopsies of the primary site. PMID- 6266304 TI - Calcium-channel blocking agents and asthma. PMID- 6266305 TI - Calcium channel blockers and Raynaud's disease. PMID- 6266306 TI - Retinoid-binding proteins of bovine retina: immunological properties. PMID- 6266307 TI - Studies on the mechanism of induction of embryonal carcinoma cell differentiation by retinoic acid. AB - On the basis of our studies, we conclude that RA is a potent promoter of differentiation of EC cells. We have demonstrated that the tumorigenicity of PCC4 azalR EC cultures can be effectively reduced following exposure of the cells to RA. This is presumably a result of differentiation of the EC cells to nontumorigenic derivatives. However, even after several weeks of exposure to RA, there remains in the culture a subpopulation of unresponsive EC cells. The reason why these cells do not differentiate in the presence of RA is currently under investigation. We have also derived by mutagen treatment and clonal selection EC cells that fail to respond to RA. Preliminary indications are that these cells have lost the capacity to differentiate when subjected to other manipulations which stimulate differentiation of the parental EC cells. This is an important observation since the mutants were selected only by their lack of response to RA. Unlike the parental cells, which have relatively large amounts of RABP, dif- cells appear either to lack RABP or to possess an altered binding protein which has a greatly reduced affinity for RA. These observations are consistent with the view that some function of the RA-RABP complex is critical in the sequence of events leading to differentiation of EC cells. However, further studies are required before we can establish the generality of this proposal. We are presently investigating whether the level and/or function of RA-RABP complexes in cells from the EC lines listed in TABLE 1 can explain their varying tendencies to differentiate. PMID- 6266308 TI - Action of retinoids and phorbol esters on cell growth and the binding of epidermal growth factor. PMID- 6266309 TI - The modulating effect of retinoids and a tumor promoter on malignant transformation, sister chromatid exchanges, and Na/K ATPase. PMID- 6266310 TI - Antiproliferative effects of retinoids related to the cell cycle-specific inhibition of ornithine decarboxylase. AB - The induction of ornithine decarboxylase (ODC) during G1 phase of the cell cycle appears to be universal and essential for cell cycle progression. This induction has been demonstrated in at least 23 cell types in response to various growth stimuli. Further, specific inhibitors of ODC added to several of these cell lines resulted in inhibition of cell proliferation. The studies of the effects of retinoids to inhibit Chinese hamster ovary (CHO) cell growth indicate that the cells are blocked in G1 of cell cycle, and that there is a concentration dependent inhibition of ODC induction. Retinoids only inhibit the induction of ODC activity when added in the first 2-3 hr of G1 progression. It is postulated that ODC induction is a requirement for G1 progression and that the antiproliferative properties of retinoids are related to the specific ability to inhibit this expression. Since retinoids do not dramatically alter the rate of protein synthesis, their ability to inhibit ODC may be related to their ability to inhibit messenger RNa synthesis for ODC. PMID- 6266311 TI - Specific and nonspecific alterations in membrane microviscosity induced by retinoids in embryonal carcinoma and fibroblast cells. PMID- 6266312 TI - Binding of retinoids to human fibroblast cell lines and their effects on cell growth. PMID- 6266313 TI - Cellular and subcellular uptake of retinoic acid and its mediation by retinoic acid-binding protein. PMID- 6266314 TI - A novel cellular retinoid-binding protein, F-type, in hepatocellular carcinoma. PMID- 6266315 TI - Nanosecond fluorometry and the luminescence of biological macromolecules. PMID- 6266317 TI - Quantum chemical studies of molecular features and receptor interactions that modulate opiate agonist and antagonist activity. PMID- 6266316 TI - Dynamics of hormone receptors on cell membrane. PMID- 6266318 TI - A survey of x-ray diffraction studies of enzyme-other molecule interactions as possible models for receptor sites. AB - In the absence of a structure for a hormone-receptor complex, one may ask what systems of known structure are most likely to provide information about hormone interactions. Here, I discussed enzyme-substrate, enzyme-(protein) inhibitor, enzyme fragment (S peptide), and antibody-hapten (or antigen) interactions as possible models. Following a study of a fairly inflexible hormone (insulin) and of a flexible hormone (glucagon), I commented on probable binding regions. Finally, my conclusion was that, at present, allosteric enzymes have many of the characteristics thought to be present in those hormone-receptor interactions which activate enzymes. This model does not necessarily apply in detail to examples of hormone interactions that affect permeability of the cell wall or activate genetic processes. PMID- 6266319 TI - The catalytic function of active site amino acid side chains in well characterized enzymes. AB - Although the kinetics and types of reactions carried out by enzymes have been established for some time, the detailed chemistry performed by these catalysis is largely unknown. Their geometries and compositions are very different from those found in conventional chemistry and understanding their mechanisms will open new areas of chemistry and make important contributions to the rational design of pharmaceuticals. We have formulated a computational method for determining the electronic role of amino acid residues in the active sites of enzymes that have been well characterized by high resolution spectroscopy and other physical chemistry techniques. Ab initio electronic structure calculations with a good basis set were employed, and solvent and dielectric effects were taken into account. Applications were made to ribonuclease A, the serine proteases, the labile hydrogen bonds in acid proteases (pepsin), and carbonic anhydrase. PMID- 6266321 TI - Quantum chemical studies of proton transport through biomembranes. AB - A proposed mechanism of proton transport through biological membranes was investigated with the aid of ab initio molecular orbital methods. It requires the existence within a transmembrane protein of a hydrogen-bonded chain of residues. The full transport process was broken down into a number of simpler steps, each of which involves the transfer of a proton from one residue to the next along the chain. The hydroxyl-containing residues were modeled by water molecules. Linear hydrogen-bonded systems H+ (H2O)n, n = 2, 3, 4, 5 were studied using the 4-31G basis set. The dimer was shown to furnish an excellent model for study of proton transfer in larger systems. Deformations of the hydrogen bond lead to large increases in the energy barrier to proton transfer. Certain properties of the electron density distribution show a close correspondence with transfer energetics; consequently, they may have some predictive use. The transition state to double proton transfer in the trimer and pentamer involve partial transfer of only one proton. Implications of the above observations upon the proposed mechanism were discussed. PMID- 6266320 TI - Theoretical studies of oxygen binding. AB - We discussed the bonding of O2 to hemoglobin using results of ab initio calculations of idealized portions of the Hb molecule. The bond between Fe and O2 is formed by coupling a triplet state (intermediate spin state) of Fe to the triplet ground state of O2 (analogous to the bonding of O to O2 in ozone). The coordination sphere of the Fe reduces the energy separation between the quintet, triplet, and singlet states, making an intermediate spin state accessible for bond formation. This provides the mechanism by which an O2 molecule can easily and reversibly bind to Hb. Neither the diamagnetic (t2g) excited state of Fe nor the excited singlet state of O2 play a role in the formation of the FeO2 bond. We also discussed the role of the Fe intra-atomic exchange terms and show how they serve to store electronic energy upon bond formation. An example was given, illustrating how this stored electronic energy can then be used to drive enzymatic reactions. Metal atoms such as ferrous Fe are capable of existing in several distinct electronic configurations, depending upon the ligands. Our objective here has been to illustrate the different characteristics of these Fe configurations and to indicate why various axial ligands stabilize particular Fe configurations. In addition, we have sketched the type of orbital descriptions arising from theoretical wavefunctions and illustrated how to use these descriptions to predict chemical phenomena. PMID- 6266322 TI - [Determination of the accumulation of nitrates in plant tissues]. AB - Nitrate accumulation in the plant represents the difference between nitrate absorption and their use. The absorption depends essentially on the available nitrate supply to the plant. We can distinguish two sources of nitric nutrition: mineral nitrogen fertilising of the crop under consideration, and mineralization of the soil organic nitrogen. While the former is directly dependent on us, the latter can hardly be controlled in terms of quantity as well as timing of the supply. On the basis of an example it is shown that the latter source of supply, as compared to mineral nitrogen fertilizing, sometimes leads to an abnormal accumulation of nitrates when the time of supply (mineralization) is not in conformity with the crop requirements during the corresponding period. The use of nitrates obviously depends on the specific physiology and the conditions affecting plant nutrition. We think that nitrate accumulation in the leaves is linked to the relative importance of nitrate metabolism in the roots and in the leaves. The tendency of various plant component to accumulate nitrates is also discussed on the basis of a few examples. PMID- 6266323 TI - [Adjustment of nitrogen fertilization to the needs of plants and limitations posed by the risk of nitrate accumulation and pollution of the soil and subsoil]. AB - In chalky Champagne, nitrogen balance is study to adjust availability to plant response. For this, it is necessary to know some parameters whose measurement is obtained progressively; plants exportation, nitrogen transformations in terms of transport processes in soil system, kinetic of mineralization of soil organic nitrogen, plants residus and agricultural waste waters. Lysimeters with rotation of Champagne (wheat, sugarbeet, potatoes...) are used to measure losses of nitrogen and follow transport of nitrates by mean of soil solution captors. Comparisons with field results, lysimeters results and laboratory experimentations are used to adjust an experimental model. Two examples show: 1) Nitrogen fertilizer requirement for wheat. 2) Possibility of maximum application for agricultural waste waters. PMID- 6266324 TI - [Effect of nitrogen fertilization and time of the harvest on the production and content of nitrates in fresh bean pods (Phaseolus vulgaris L. var. Coco nain)]. AB - French beans were cultivated under different nitrogen fertilizer levels for fresh pods production. Pods were collected after different time intervals. Fresh weight of pods, number and nitrate nitrogen content were determined. Results are presented and discussed. They bring some informations about better cultivation methods to avoid a too high nitrates content in pods. PMID- 6266325 TI - [Evaluation of 5 years' experimentation on the lowering of the nitrate content of carrots]. AB - From essential results have been obtained since 1971 in collaborative studies with E.N.S.A.I.A. de Nancy, F.N.I.E. et I.N.R.A. d'Antibes. If you have a nitrates low level in carrots, with average lower than 250-300 mg/kg; its necessary to choose ground with poor amount of organic matter (about less than 2%). Otherwise the practice of a strong irrigation, 15 days before the harvest, can lower nitrate level in quantity. PMID- 6266326 TI - On the determination of crystalline silica in the presence of amorphous silica. PMID- 6266327 TI - [Interest of ultrastructural study of skin and muscle biopsies in inborn storage diseases. A report of 18 cases (author's transl)]. AB - Skin and muscle biopsies were performed in 18 patients affected by various inborn storage disorders: mucopolysaccharidosis (MPS), sphingolipidosis, GM1 gangliosidosis, I-cell disease, ceroid-lipofuscinosis (CLF), adrenoleucodystrophy (ALD) and glycogenosis. In most cases, cutaneous and muscle biopsies demonstrate clearly the presence of storage inclusions in different cell types with great reproducibility and sometimes a specificity for a particular disease. Thus, electron microscopic examinations of skin and muscle, often complementary, can given valuable informations at two levels: - either a morphological confirmation depending on the type of the storage disease: e. g. clear, granular and fuzzy inclusions identified with mucopolysaccharidic material, lamellar and pseudomyelinic figures corresponding to lipidic structures are found in different cell types in MPS, gangliosidosis and sphingolipidosis; - or a diagnostic proof of some lysosomal diseases where there are very specific ultrastructural features such as the curvilinear bodies and fingerprint profiles in CLF or the spicular inclusions in ALD. These informations are the more important as the enzymatic defect is unknown in these inherited disorders. We conclude that the ultrastructural examination of a skin and muscle biopsy are an important tool for the diagnosis of a lysosomal storage disease which avoids any more difficult biopsies as brain, kidney, liver. PMID- 6266328 TI - [Rotavirus and acute gastroenteritis in childhood: a one-year survey in a department of general pediatrics (author's transl)]. PMID- 6266329 TI - [The influence of synthetic oestrogens on experimental Schistosoma mansoni parasitosis in hamster: studies of the effects of hexestrol and chlorotrianisene (author's transl)]. PMID- 6266330 TI - [Attempt to induce diarrhea in young rabbits with different dietary crude fiber contents (author's transl)]. AB - The influence of five diets containing 14.5, 10, 6.9, 4.6 and 3.3 per cent of crude fiber was studied in 6-week-old rabbits. Two additional groups of animals fed with the rations with 14.5, 6.9 and 3.3 per cent crude fiber were used. The first was inoculated with coccidia, the second was treated with ampicillin. In non-inoculated and untreated rabbits, diarrhea was inconstant, of short duration and low intensity and appeared only for cellulosis rate less than 4.6 per cent. There was no mortality. Decrease in the dietary crude fiber level cannot be considered as directly responsible for digestive ailments, when sanitary conditions are good. In our experimental conditions, it has been shown that a low level of cellulosis in the diet did not increase the pathological phenomena. Inversely pathogenic elements (coccidia) or medicaments used (ampicillin) can change the relations which exist between growth and components of the diet (cellulosis). PMID- 6266331 TI - Prostaglandins as probable mediators of the suppression of antibody production by mouse hepatitis virus infection. PMID- 6266332 TI - A comparison of stapedial reflex fatigue with repetitive stimulation and single fiber EMG in myasthenia gravis. AB - The pattern of stapedial reflex fatigue in response to pulsed acoustic stimulation was measured and compared to results of repetitive nerve stimulation and single-fiber electromyography (EMG) in 89 patients with myasthenia gravis. Studies were also made on 22 patients with other neuromuscular disorders and 40 control subjects with no evidence of neuromuscular impairment. Stapedial reflex fatigue exceeded normal control values in 84% of the patients with myasthenia gravis. Repetitive stimulation and single-fiber EMG measurements were abnormal in 56% and 91% of this same population, respectively. Stapedial reflex abnormalities were most prevalent in patients with mild forms of myasthenia (predominantly ocular or oropharyngeal weakness). Of 22 nonmyasthenic patients with neuromuscular disease tested, 6 had abnormal stapedial reflex fatigue according to our normal values, indicating that this form of testing also detects other diseases of the motor unit. The measurement of stapedial reflex fatigue is painless, is easy to perform, and requires minimal patient cooperation. Due to the relatively high occurrence of abnormal stapedial reflex fatigue in patients with myasthenia gravis, this procedure appears to have considerable potential value in screening and monitoring patients for the presence of defects in neuromuscular transmission. PMID- 6266333 TI - Prolonged intracerebral infection with poliovirus in asymptomatic mice. AB - A heretofore unrecognized prolonged asymptomatic infection has been identified in mice intracerebrally inoculated with Lansing strain type II poliovirus. Virus was detected by infectivity assay and nucleic acid hybridization and was found in brains as long as 77 days after injection. Viral RNA replication occurred, indicating that persisting virus was not an inactive residuum of the infecting dose. Virus was sometimes found by infectivity even when viral RNA could not be demonstrated by hybridization, but detection by nucleic acid hybridization alone never occurred. Among 56 animals--including mice that died of infection, mice with prolonged infection, and survivors from which virus was not recovered--no animal had a serum neutralization titer above 1:2 in a plaque reduction assay Moreover, brain homogenates of 30 survivors without virus did not have neutralization titers above 1:4 in the plaque reduction assay. These findings were the same as in mock-infected mice. PMID- 6266334 TI - EPR determination of membrane potentials. PMID- 6266335 TI - Nerve sodium channel incorporation in vesicles. PMID- 6266337 TI - Improved method for virological analysis of food. AB - A single, simple method for recovering enteroviruses from several different kinds of food, such as ground beef, fish, oysters, and mussels, has been improved. First, sample contamination technique was studied. It appears that virus adsorption occurs at food pH and varies according to the kind of food and the food-virus exchange surface. Second, virus recovery was evaluated. According to the experimental results obtained, we propose the following method. Samples are submerged in 100 ml of demineralized water adjusted to pH 9 with a conductivity of 8,000 mg of NaCl per liter. Then, viruses are concentrated by ultrafiltration or by ultracentrifugation. This method was efficient for virus recovery from the four kinds of food, even in cases of very low contamination. PMID- 6266336 TI - Relationship of sporulation, enterotoxin formation, and spoilage during growth of Clostridium perfringens type A in cooked chicken. AB - Sporulation and enterotoxin formation were determined for 17 strains of Clostridium perfringens type A in autoclaved chicken dark meat and in Duncan Strong sporulation medium. The mean numbers of heat-resistant spores detected after 24 h at 37 degrees C were log10 1.13 to log10 7.64/ml in Duncan-Strong medium and log10 4.93 to log10 6.59/g in chicken. Of 17 strains, 7 formed enterotoxin in Duncan-Strong culture supernatant (1.0 to 60 microgram/ml) and 8 produced enterotoxin in chicken (0.21 to 24 microgram/g). Additional studies with chicken were conducted with C. perfringens NCTC 8239. With an inoculum of 10(6) cells per g, greater than log10 7.99 vegetative cells per g were detected by 4 h in chicken at 37 degrees C. Heat-resistant spores occurred by 4 and 6 h and enterotoxin occurred by 8 and 6 h in autoclaved chicken dark meat and barbecued chicken drumsticks, respectively. Enterotoxin was detected in autoclaved dark meat after incubation at 45 degrees C for 1.5 h followed by 37 degrees C for 4.5 h, but not after incubation at 45 degrees C for 1.5 to 8 h. With an inoculum of 10(2) cells per g in oven-cooked or autoclaved chicken, greater than log10 8.00 vegetative cells per g were detected by 6 to 8 h at 37 degrees C, heat-resistant spores were detected by 8 h, and enterotoxin was detected by 12 h. A statistical analysis of odor determinants of chicken after growth of C. perfringens indicated that, at the 95% confidence level, the product was considered spoiled (off or unwholesome odor) by the time spores or enterotoxin were formed. PMID- 6266338 TI - Effect of soil permeability on virus removal through soil columns. AB - Laboratory experiments were performed on four different soils, using 100 cm long columns, to determine the extent of virus movement when wastewater percolated through the soils at various hydraulic flow rates. Unchlorinated secondary sewage effluent seeded with either poliovirus type 1 (strain LSc) or echovirus type 1 (isolate V239) was continuously applied to soil columns for 3 to 4 days at constant flow rates. Water samples were extracted daily from ceramic samplers at various depths of the column for the virus assay. The effectiveness of virus removal from wastewater varied greatly among the different soil types but appeared to be largely related to hydraulic flow rates. At a flow rate of 33 cm/day, Anthony sandy loam removed 99% of seeded poliovirus within the first 7 cm of the column. At flow rates of 300 cm/day and above, Rubicon sand gave the poorest removal of viruses; less than 90% of the seeded viruses were removed by passage of effluent through the entire length of the soil column. By linear regression analyses, the rate of virus removal in soil columns was found to be negatively correlated with the flow of the percolating sewage effluent. There was no significant difference in rate of removal between poliovirus and echovirus in soil columns 87 cm long. The rate of virus removal in the upper 17 cm of the soil column was found to be significantly greater than in the lower depths of the soil column. This study suggests that the flow rate of water through the soil may be the most important factor in predicting the potential of virus movement into the groundwater. Furthermore, the length of the soil column is critical in obtaining useful data to predict virus movement into groundwater. PMID- 6266339 TI - [Dietary fiber in food products. Its importance for public health]. PMID- 6266340 TI - Characterization of three rabbit liver lysosomal proteinases with fructose 1,6 bisphosphatase converting enzyme activity. PMID- 6266341 TI - Interactions of a 5-nitroxide-labeled poly(uridylic acid) with poly(adenylic acid). PMID- 6266342 TI - Induction of calcium-binding protein in organ-cultured chick intestine by fluoro analogs of vitamin D3. PMID- 6266343 TI - Identification of neutral and anionic 8 alpha-substituted flavin semiquinones in flavoproteins by electron spin resonance spectroscopy. PMID- 6266344 TI - Characterization of ubisemiquinone radical in the cytochrome b-c1 segment of the mitochondrial respiratory chain. PMID- 6266345 TI - Mechanism of vesicular stomatitis virus mRNA decay. PMID- 6266346 TI - Enzymatic dephosphorylation of endogenous and exogenous dolichyl monophosphate by calf brain membranes. PMID- 6266347 TI - A cellular activator of catecholamine-sensitive adenylate cyclase in rat reticulocytes and erythrocytes: changes during reticulocyte development and effects on the beta receptor. PMID- 6266348 TI - The stoichiometric activation of human skin fibroblast pro-collagenase by factors present in human skin and rat uterus. PMID- 6266350 TI - ADP-ribosylation of trout testis chromosomal proteins: distribution of ADP ribosylated proteins among DNase I-sensitive and -resistant chromatin domains. PMID- 6266349 TI - Role of iron and ethylenediaminetetraacetic acid in the bactericidal activity of a superoxide anion-generating system. PMID- 6266351 TI - Control of substrate cycling at fructose phosphates in a reconstituted muscle glycolytic system. PMID- 6266352 TI - Phosphoglycolate phosphatase from human red blood cells. PMID- 6266353 TI - The enzymology of DNA replication. PMID- 6266354 TI - Laser treatment of multiple glomangiomas: progress report 13 years after treatment. PMID- 6266355 TI - Trauma affects cyclic AMP and DNA levels at injured and non-injured distal oral mucosal sites. AB - Experiments in rats were conducted to test the hypothesis that gingival trauma affects cyclic AMP and DNA levels at the gingival wound, and non-injured distal (gingival, palatal) sites. Cyclic AMP and DNA levels rose and fell in a cyclic fashion during the time (0.5-24 h) periods analyzed. Significant increases in cAMP levels occurred at 8 and 20 h and at 8 and 16 h, respectively, at the wound and non-injured palatal site, peripheral to the wound. Similar increases (not significant) in cAMP levels were also noted at the non-injured gingival contralateral site at the same time intervals. DNA distributions were found to be significantly greater 10 and 16 h after injury at the gingival wound, and distal non-injured gingival and palatal sites. PMID- 6266356 TI - [A new case of carcinoma arising in Caroli's disease (author's transl)]. PMID- 6266357 TI - The effect of preload on the dissociation constant of phentolamine in isolated rabbit thoracic aorta. AB - The affinity of phentolamine for the alpha-adrenergic receptor of isolated rabbit thoracic aorta was determined under two different preload conditions. In one condition, strips or rings or aorta were preloaded with a 1/4 g weight; in the other condition, with a 10 g weight. To measure affinity, dose-response curves were first obtained for agonist alone and then for agonist in the presence of various concentrations of phentolamine, a reversible alpha-adrenergic antagonist. From these curves, equieffective agonist concentrations were selected and Schild plots constructed to determine the dissociation constant (1/affinity). It was found that values of the dissociation constant, KB, for phentolamine were independent of the agonist used (norepinephrine or phenylephrine) to obtain the dose-response curves. KB was, however, a function of preload conditions. In all cases, IB at 1/4 g was greater than KB at 10 g preload. The magnitude of this difference in affinity with preload though, was less then previously obtained for agonists in the same preparation. The implications of this finding are discussed in terms of the effect of preload on receptor conformation and possible differences between agonist and antagonist binding. PMID- 6266358 TI - Inhibition and induction of microsomal enzymes in rat. A comparative study of four antimycotics: miconazole, econazole, clotrimazole and ketoconazole. AB - The interaction of four imidazole antimycotics clotrimazole, econazole, ketoconazole and miconazole with other drugs was studied in in vivo models known to reveal inhibition and induction of microsomal enzymes. In rats the duration of methohexital hypnosis and the prothrombin time prolongation induced by acenocoumarol were changed after oral administration of all four antimycotics. The oral ED50-values of miconazole, econazole and clotrimazole for prolongation of methohexital hypnosis in female rats (acute inhibiton of microsomal enzymes) were 3.55, 3.56 and 10.7 mg/kg. Ketoconazole, inhibited microsomal enzymes at the oral ED50 of 30.4 mg/kg in female and 97.0 mg/kg in male rats. After subchronic treatment only clotrimazole reduced the hypnosis time below control values (induction of microsomal enzymes); the ED50 of clotrimazole for his activity was 14.9 mg/kg. The lowest effective dose of ketoconazole for extra-prolongation of the prothrombin time was 50 mg/kg, whereas the other antimycotics showed this effect at much lower doses. The implications of these results for the therapeutic use of these compounds are discussed and it is concluded that ketoconazole can be considered to be devoid of interaction with drugs, of which the intensity and duration of action strongly depends on their metabolic transformation rate in the liver. PMID- 6266360 TI - Myasthenia gravis and premature ovarian failure. AB - Myasthenia gravis is believed to be an autoimmune disorder that results from antibodies directed against acetylcholine receptors. Not infrequently, it is associated with other autoimmune diseases, and, recently, several cases have been reported of coexistent premature ovarian failure. A 25-year-old nullgravida woman with myasthenia gravis became amenorrheic and then had ovarian failure with increased gonadotropin and negligible estrogen levels. Other endocrine functions were normal. An in vitro assay demonstrated the presence, in serum, of an inhibitor of binding to the luteinizing hormone (LH) receptor that suggested the possibility of a similar autoimmune process underlying the myasthenia gravis and premature ovarian failure. This could be the first case in which both disorders occurred with evidence for an LH receptor antagonist. PMID- 6266359 TI - Opiate agonists inhibit noradrenaline release via opiate B-receptors and N cyclopropylmethylnorazidomorphine (CAM) blocks electrically evoked contractions via histamine in the mouse vas deferens. AB - N-cyclopropylmethylnorazidomorphine (CAM) reduced slightly the stimulation evoked 3H-noradrenaline outflow from the mouse vas deferens and this effect was not antagonized by naloxone. Azidomorphine, however, inhibited potently the release of noradrenaline and the effect was completely antagonized by CAM and naloxone. The field stimulation induced release of acetylcholine remained unchanged in the presence of CAM. Atropine leaving the release of noradrenaline unchanged caused 50-60% inhibition of responses to electrical stimulation. Histamine and 48/80 inhibited the twitch responses to electrical stimulation and this effect was antagonized by H1-receptor antagonists (mepyramine, chloropyramine phenindamine, thenalidine, cyproheptadine), but not by cimetidine. H1-receptor antagonists increased the release of noradrenaline and facilitated neuromuscular transmission; cimetidine was ineffective. H1-blocking antihistamines completely inhibited the blockade of the electrically evoked contractions caused by CAM, whereas cimetidine left them unaltered. The effects of morphine and azidomorphine were only moderately antagonized by H1-blocking antihistamines and the effect of methionine enkephalin remained unchanged. In the presence of atropine and H1 blocking antihistamines CAM antagonized the effect of the opiate agonists competitively. It was concluded that in the mouse vas deferens opiate agonists inhibit noradrenaline release via opiate B-receptors. CAM inhibits the twitch responses in this test via histamine and H1-receptors were found to be involved in this mechanism. PMID- 6266361 TI - Concentration of metabolites and the regulation of phosphofructokinase and fructose-1,6-bisphosphatase in Saccharomyces cerevisiae. AB - The intracellular levels of adenosine triphosphate and several glycolytic intermediates were determined in Saccharomyces cerevisiae in relation to the presence of the metabolically antagonistic enzymes phosphofructokinase and fructose-1,6-bisphosphatase. Phosphofructokinase is synthesized constitutively in cells grown in the presence of glucose and fructose-1,6-bisphosphatase derepression occurs upon the exhaustion of glucose from the growth medium. Transcriptional regulation of fructose-1,6-bisphosphatase was suggested based on experiments with wild type cells using 8-hydroxyquinoline, a known inhibitor of nuclear transcription, and with the S. cerevisiae mutant strain A364A (ts-136) blocked in the transport of nuclear RNA at non-permissive temperature. The level of phosphofructokinase was reduced more than 25-fold under conditions of high citrate accumulation in an aconitase-less, glutamate requiring mutant strain, MO 1-9B. There was a rapid decrease in the levels of adenosine triphosphate and fructose-1,6-bisphosphate at the end of log-phase of culture growth when both fructose-1,6-bisphosphatase and phosphofructokinase were present in the cells simultaneously. The changes in the levels of key glycolytic intermediates, but not the changes in adenosine triphosphate, during the simultaneous presence of these two enzymes, can be explained without involving any futile cycling. PMID- 6266362 TI - [A case of bronchiolo-alveolar carcinoma]. PMID- 6266363 TI - [Echotomography in nephroblastoma and neuroblastoma of the lumbar fossa in childhood. Comparison with intravenous pyelography and computerized tomography (author's transl)]. AB - The respective values of intravenous pyelography, ultrasound examination and computerized tomography are compared with the findings at surgery and with histological data in 28 children with malignant tumors of the lumbar fossa. Ultrasound proved to be of significant value in assessing the extent of the tumor. At the present time, computerized tomography is only indicated when intravenous pyelography and ultrasound examination fail to provide adequate information. PMID- 6266364 TI - Cytological and biochemical methods for the characterization of in vitro cultured cells. AB - The aim of our presentation was to show how we characterize cells cultured in monolayer system. Cytological and biochemical methods were used. Ovarian Krukenberg tumour fibroblasts were investigated and findings were correlated with normal human diploids (HDZ1) and with fibroblasts obtained from Blighted ovum. Cytomorphologically Malignancy associated changes in the tumour fibroblasts were found. Cytochemically acid phosphatase and alpha-naphtyl-esterase were positive (+++). PAS reaction was doubled in 18th passage. Cytogenetically normal human diploids were found. Biochemically enzymatic assay showed phosphopentose shunt is decreased in tumour fibroblasts and alpha-glucosidase and beta-galactosidase activities were significantly lower in these cells. A form of N-acetyl-beta glucosaminidase fell during the investigation from normal 75% to lower percent (42% of the total activity). Much more parameters were obtained by different methods and Krukenberg tumour fibroblasts may be better understood. In vitro investigation makes a contribution to biomedical knowledge in cancer research. PMID- 6266365 TI - Possible role of accessibility of protein-SH groups to the cancer state. AB - From out histochemical studies, protein-sulfhydryl (SH) groups are found mainly concentrated in the nucleus and in cell nuclear membranes. Both clinically and in sensitivity tests, selected SH inhibitors have been found to be more active than other commonly used anticancer agents, against an array of cancers, than against normal tissues. The same SH inhibitors can induce immunity against some cancers in animals, while causing blunting of microvilli and alterations in cell surface of the cancer cells. From recent electron spin resonance data (ESR), selected SH inhibitors and glyoxal derivatives can raise the low ESR signal of cancers towards or above normal. The variety of important roles of protein-SH groups to the cancerous state underscores the possible role of accessibility of protein-SH groups to cancer. This very importance of protein-SH groups to cancer, with their highly variable chemical reactivity, underscores also the lack of validity of randomized protocols for clinical cancer therapy. None of these take into account any measure of the chemical sensitivity of each patient's own cancer. PMID- 6266366 TI - Different changes in transmembrane potential of cultured cells after ouabain inhibited active Na+/K+-transport. AB - The inhibition of (Na+/K+) activated membrane ATPase by cardiac glycosides is electrophysiologically detectable in terms of a reduction of the transmembrane potential (TMP) of cells. Two hours after incubation in medium with 10(-4) mole/l ouabain added, the TMP of cells were measured by means of glass microelectrodes. Compared with untreated controls, HeLa and FL-cells, human embryo cells, skin fibroblasts, leukocytes, and exudate macrophages without exception showed a TMP reduction typical of the particular cell kind. Primary cultures of human embryo cells and skin fibroblasts revealed the highest sensitivity (approx. 60% TMP reduction), while lesser and relatively low sensitivities were observed for permanent cells (approx. 30% TMP reduction) and white blood cells (approx. 20% TMP reduction), respectively. Unlike the above, the ovarian tumor cells showed inter-individually varied reactions within the range of TMP changes from - 55% to + 33%. The majority of malignant tumours, in particular, exhibited only a weak reaction in the ouabain test or no reaction at all. On the other hand, ovarian cysts or other clinically benign tumors showed the normal ouabain effect. The experimental results obtained for the ovarian tumors are believed to demonstrate a defect of one or several transport enzymes, which effect is associated with the malignancy of cells and may be used as a functional in vitro marker for malignancy in the field of cell physiology. PMID- 6266367 TI - Effect of histamine on the spontaneous rosette formation. AB - Eight persons with clinically diagnosed hay fever were examined. The control group consisted of ten subjects without any signs of allergy. T lymphocyte subpopulation was evaluated by E rosette test. The effect of histamine was studied adding various concentrations of histamine (from 10(-9) to 10(-4) M) to the suspension of lymphocytes. A proportional drop in the percentage of the formed E rosettes could be seen at histamine concentrations ranging between 2 x 10(-9) and 2 x 10(-6) M. At 10(-6) up to 10(-4) M there was both an increase and further reduction in the percentage of the E rosette formation. A question arises whether there exists any correlation between the decreased number of T lymphocytes and elevated content of histamine in atopic persons? PMID- 6266369 TI - Atypical bronchial carcinoid with oncocytoid features. Its ultrastructure, with special reference to its granular content. AB - A case of atypical bronchial carcinoid with oncocytoid features was studied. The tumor contained mitochondria-laden cells with scanty neurosecretory granules, heavily granulated cells, and intermediate forms. The neurosecretory granules were of three types as reported in previous cases: type P, type 3, and a double core granule. The ultrastructural findings are characteristic of this type of tumor. PMID- 6266368 TI - Effect of histamine on the spontaneous E rosette formation after blockade of histamine H2 receptors with cimetidine. AB - Thirteen patients with clinical diagnosis of hay fever, were examined. T lymphocytes subpopulation was determined by the E rosette test. The present study is concerned with the effect of histamine on the ability of T lymphocytes for E rosette formation after blockade of the histamine H2 receptor with its inhibitor cimetidine. It has been found that histamine effect is expressed by the histamine H2 receptor, as its blockade with cimetidine leads to the failure of histamine to inhibit rosette formation by T lymphocytes. PMID- 6266370 TI - M-response quantification: a technique. AB - Median nerve responses in 13 patients and 9 normal subjects were evaluated using surface bipolar stimulation. The M response from surface electrodes placed upon the thenar eminence was recorded on a fiberoptic chart recorder and simultaneously subjected to true electronic integration. Comparison between the integrated M response and the M index (the product of the M response peak-to-peak amplitude and total duration) revealed a highly correlated linear regression. This linear relationship was present when stimulating both at the wrist (r2 = 0.96) and the antecubital fossa (r2 = 0.95). Statistically significant differences were observed between the integrated M response of 5 normal adult men and men with carpal tunnel syndrome (n 3, p less than 0.01) or anterior horn cell or neuropathic processes (n 4, p less than 0.001). Differences of borderline significance were noted between normal women (n = 4) and women with carpal tunnel syndrome (n 4, p less than 0.05) or anterior horn cell or neuropathic processes (n 2, p less than 0.01). There was no correlation between the integrated M response and the distal latency in patients with carpal tunnel syndrome. It is concluded that the M index is a highly reliable method of quantifying the M response as an approximation of integration in median nerve studies, but that this measurement holds little relationship with the presence of the distal neuropathic processes studied. PMID- 6266372 TI - Effect of single and repeated administration of delta 9-tetrahydrocannabinol on 5 hydroxytryptamine, noradrenaline, dopamine and tryptophan levels in the brain of Wistar rats. PMID- 6266371 TI - [Niemann-Pick disease type C (subacute neurovisceral lipidosis). Problems of altered sphingomyelinase activity in the brain (author's transl)]. AB - One fetus (20 weeks old) and two postnatal cases with Niemann-Pick disease type C (a group of unclear neurovisceral lipidoses characterized by foam cells in the bone marrow and sometimes supranuclear ophthalmoplegia) were studied with respect to the pH-dependency of brain sphingomyelinase activity. A distinct reduction of activity in the pH 5 range of the fetus was contrary to an almost normal pH profile in the postnatal cases including the sibling of the fetus. The sphingomyelinase anomaly does not seem to reflect the genetic defect, since it is paralleled by a similar anomaly of glucocerebrosidase activity. A pathologic subcellular localization of more than one lipid hydrolasis is discussed. PMID- 6266373 TI - Ocular sarcoidosis. PMID- 6266374 TI - Sarcoidosis of the lacrimal sac. AB - Two women with acute dacryocystitis were found to have noncaseating granulomatous inflammation of the lacrimal sac and nasal mucosa. One patient had chronic uveitis and the other had skin lesions and generalized lymphadenopathy histologically compatible with sarcoidosis. The diagnosis was supported by elevation of serum levels of angiotensin-converting enzyme. To our knowledge, these are the sixth and seventh histologically confirmed cases of sarcoidosis of the lacrimal sac. They differ from previously reported cases in the absence of classic roentgenographic changes of sarcoidosis. Analysis of all reported cases suggests an association between lacrimal sac and upper respiratory tract sarcoidosis. PMID- 6266375 TI - Ganglionic herpes simplex and systemic acyclovir. AB - The therapeutic and systemic effects of acyclovir on ganglionic herpes simplex virus (HSV) in mice were studied by varying the duration of treatment and the time of removal of ganglia for co-cultivation after treatment had ended. When treatment was started three hours after infection, it had a significant therapeutic effect even when the ganglionic culture was delayed 17 days after the end of acyclovir therapy. When treatment was started 24 hours after infection, it had no significant effect under the same circumstances. The treatment of established latent ganglionic HSV for 15 days with acyclovir had a significant therapeutic effect compared with control mice when ganglia were cultured two days after treatment had ended, but this effect was lost by ten and 21 days after the end of therapy. This indicates that acyclovir has a transient suppressive effect on part of the viral ganglionic reservoir, but it also indicates that these titers quickly reestablish themselves with the removal of drug therapy. PMID- 6266377 TI - The current status of the vitamin D metabolites. AB - Research over the last fifteen years has led to the identification of several metabolites of vitamin D, elucidation of their mechanism of action, clarification of the pathogenesis of several metabolic bone diseases, and development of new diagnostic tests and more effective and safe treatment. 1, 25(OH)2 D, the most active metabolite, can be regarded as a highly potent steroid hormone, with its formation from its precursors tightly coupled to physiological need by a variety of ionic and hormonal regulating mechanisms. PMID- 6266378 TI - Growth, renal osteodystrophy and vitamin D therapy in children with chronic renal failure. PMID- 6266379 TI - Vasoactive peptides and hypertension: role of angiotensin converting enzyme. AB - Angiotensin converting enzyme plays a key role in the hormonal regulation of blood pressure. It is responsible for the production of the vasoconstrictor hormonal peptide angiotensin II as well as the destruction of the vasodilator peptide bradykinin. Recently, orally active specific inhibitors of angiotensin converting enzyme have become available. Captopril (SQ14225) blocks angiotensin I and potentiates bradykinin effects in vitro and in vivo. In man it leads to a fall in endogenous plasma angiotensin II, a rise in blood angiotensin I and renin, but no change in blood bradykinin can be detected. In sodium deplete normal subjects it lowers the blood pressure, but in sodium replete subjects it is without effect. Similarly, it will acutely lower blood pressure in renovascular and accelerated hypertension but not in essential hypertension. The acute hypotensive effect of captopril may therefore be due to inhibition of the renin-angiotensin system. However, in the long term, it is effective in lowering the blood pressure in patients with essential hypertension, especially when combined with a diuretic. This suggests that the long-term hypotensive effect differs from the short term effect, and involves mechanisms other than inhibition of the renin-angiotensin system. This may include local effects on blood vessels and the kidney and the kallikrein-kinin system. PMID- 6266380 TI - Liver resection for neoplasm. AB - Major hepatic resections can now be performed with much greater safety than formerly. This is largely a consequence of improved surgical and anesthetic techniques, which have in turn resulted from better understanding of the anatomy, physiology and biochemistry of the liver. The treatment of liver tumours by resection must be reappraised in the light of these advances. This paper reports twelve patients who have undergone major hepatic resection for neoplasm at the Royal Prince Alfred Hospital over a ten-year period. The current indications for such surgery in the treatment of benign and malignant liver tumours are reviewed, and the results discussed. PMID- 6266381 TI - The effect of equine coital exanthema on the fertility of mares covered by stallions exhibiting the clinical disease. AB - The effect on the fertility of mares during two outbreaks of equine coital exanthema have been described. Conception was not prevented, nor was pregnancy terminated in mares showing active lesions of coital exanthema. Normal pregnancy rates occurred in mares served during active infection of the stallions. Origin of the disease was not determined. PMID- 6266382 TI - Feline respiratory virus carriers in clinically healthy cats. AB - In two surveys, feline calicivirus was cultured from 19.7% and 15% of 66 and 201 clinically healthy cats respectively. Feline viral rhinotracheitis virus was cultured also from 1.5% of oropharyngeal swabs collected in both surveys. Feline syncytial virus was isolated from 5.5% oropharyngeal swabs collected in the second survey. The use of serological examination and corticosteroid treatment to stimulate virus shedding demonstrated that 25.8% cats in the first survey were carriers of feline viral rhinotracheitis virus. In the second survey, mercapto ethanol treatment of serum was used to differentiate recent from previous infection with feline viral rhinotracheitis virus and some 18.5% cats had FVR antibody that was resistant to treatment with mercapto-ethanol. PMID- 6266383 TI - Replication of infectious laryngotracheitis virus in chickens following vaccination. AB - The site of replication of infectious laryngotracheitis vaccine virus (ILTV) was studied in chickens vaccinated by drinking water (DW), intraconjunctival (IC) and cloacal (CL) routes. The anatomical sites exposed to vaccine were determined by simulating vaccination with rhodamine red dye. Virus replication was determined by recovering virus from various organs at necropsy. The dye simulation studies clearly demonstrated that DW vaccination did not usually expose susceptible target organs to virus while the CL and IC routes flooded susceptible organs with vaccine. Virus replication was confined to the cloaca in CL vaccination birds while in IC and DW vaccination birds most replication took place in the nasal cavity. Vaccine virus did not always become established in DW vaccinated birds and its establishment did not appear to be related to the amount of vaccine these birds were exposed. It was concluded that DW vaccination depends for its success upon the accidental contamination of the nasal cavity with vaccine virus during the act of drinking. PMID- 6266384 TI - Involvement of adenovirus in pneumonia in a thoroughbred foal. PMID- 6266385 TI - Differentiation of sub-types of equine herpesvirus I by restriction endonuclease analysis. PMID- 6266386 TI - Viral encephalomyelitis of pigeons. VI. Some physico-chemical properties of the virus and extracted viral DNA. AB - Pigeon herpes encephalomyelitis virus (PHEV) was stable at -70 C for at least 4 months. When stored at -20 C, the virus lost 80% of its infective titers in 4 months. When stored at -10 C, however, the titers decreased rapidly; no detectable virus remained within 12 weeks. PHEV was thermolabile: it was completely inactivated at 56 and 60 C for 10 and 2 min respectively. It was also killed by 1% cresol and 2% sodium hydroxide for two hr and 2% septol for 24 hr. Two-percent phenol or formaline for 2 hr, however, significantly decreased virus infective titers. Phenol-purified DNA extracted from PHEV showed an ultraviolet spectrum of typical nucleic acids that had ratios of absorbancies at 265 nm/280 nm between 2 and 2.3. The extracted viral DNA was infectious in chorioallantoic membrane and chick embryo fibroblast cell cultures, but it was not noninfectious when given to pigeons. DNA infectivity was destroyed by DNAse but not RNAse treatment. Extracted DNA was not neutralized by antiserum against the intact virus, and it lost its infectivity property when heated at 70 C for 10 min. PMID- 6266387 TI - Effect of infectious bursal disease virus infection on the phagocytosis of Staphylococcus aureus by mononuclear phagocytic cells of susceptible and resistant strains of chickens. AB - Studies were conducted to determine why chickens infected with infectious bursal disease (IBD) are more susceptible to Staphylococcus aureus. We evaluated the effect of IBD virus on functions of the peripheral mononuclear phagocytes and looked for humoral abnormalities in the serum. An in vitro opsonophagocytic assay using (H3) thymidine-labeled opsonized Staphylococcus aureus was used to measure phagocytosis. Infection of IBD-sensitive (SCWL 420) chickens with IBD virus did not cause any cellular defects, as shown by phagocytic inability, or any humoral abnormalities, as shown by the lack of opsonics. However, IBD virus did cause some humoral defects 2 weeks postinfection in resistant (Hardy Red) chickens. Therefore, the basic mechanisms governing increased susceptibility of IBD infected chickens to S. aureus is still unknown. PMID- 6266388 TI - Tolerance, viral shedding, and neoplasia in chickens infected with non-defective reticuloendotheliosis viruses. AB - Chickens inoculated as embryos with non-defective reticuloendotheliosis viruses (ndREVs) generally developed a "tolerant" infection characterized by lack of immunofluorescent antibody and by a viremia that persisted through 93 weeks. Chickens inoculated at hatching generally developed a "non-tolerant" infection characterized by antibody development that gradually waned as the chickens aged and by a transient or intermittent viremia. Although chickens tolerantly infected with ndREV strain T were immunodepressed, tolerance to ndREVs did not depend on immunodepression, because 17-to-20-week-old chickens tolerantly infected with ndREV strain CS were normal in antibody response to sheep red blood cells and Brucella abortus and in mitogen-stimulated blastogenesis of blood lymphocytes. Tolerantly infected dams shed low levels of gs antigen and virus into eggs at high frequencies; however, in two trials, congenital transmission of virus by strain-CS-infected dams was documented in only 2 of 42 and 1 of 132 progeny chicks. Eggs and progeny chicks from non-tolerantly infected dams were always negative for virus and gs antigen. After long latent period (17 to 93 weeks), ndREV-infected chickens developed lymphomas involving the bursa of Fabricius and other visceral organs at high frequency and developed sarcomas, carcinomas, and inflammatory nerve lesions at a lower frequency. The ability of ndREVs to induce tolerant and non-tolerant infection, virus- and antigen-shedding into eggs, and chronic neoplastic disease resembled that of lymphoid leukosis virus, another common avian retrovirus. Certain differences in epidemiological properties of these 2 viruses are discussed. PMID- 6266389 TI - Local antibody response in avian infectious bronchitis: virus-neutralizing antibody in tracheobronchial secretions. AB - Specific-pathogen-free chickens were tested for local antibody response after respiratory exposure to live avian infectious bronchitis virus (IBV). Tracheobronchial secretions were obtained after intraocular-intratracheal vaccinations with Holland and Massachusetts 41 strains IBV. Low levels of immunoglobulin (Ig)A and IgG virus-neutralizing antibodies were detected in secretions after each of two vaccinations with a moderate dose (10(4) EID50), neutralizing activity in secretions was found mainly in IgG antibody. Only challenge exposure to Holland IBV resulted in a marked secondary secretion antibody response. PMID- 6266390 TI - Hemorrhagic enteritis: virus distribution and sequential development of antibody in turkeys. AB - Turkeys poults were inoculated intraperitoneally with hemorrhagic enteritis virus (HEV) at 4-1/2 weeks of age. Antibody response and sequential development of viral antigen in various tissues were monitored. An enzyme-linked immunosorbent assay (ELISA) was developed to study antibody production, and immunoperoxidase staining was used to determined sites of localization of the viral antigens in tissues. Results of ELISA and immunodiffusion tests were compared. ELISA detected antibody from day 3 post-infection (p.i.), and gel diffusion detected antibody from day 5 p.i. Peak ELISA antibody titer appeared from day 14 p.i. HEV antigen was detected from 2-6 days p.i. in the spleen, liver, intestine, kidney, and bone marrow; peak titers in the spleen were on day 3 p.i. Virus was not detected after day 6 p.i. PMID- 6266391 TI - Isolation of surface tubules of fowlpox virus. AB - Surface tubules of fowlpox virus were isolated using chemical and physical methods. Suspensions of lipid cytoplasmic inclusion bodies were obtained by treating infected chorioallantoic membranes with 1% trypsin. Inclusions were treated with ultrasonic sound, detergents, and enzymes and were examined by electron microscopy. Although lipase treatment altered the morphology of lipid inclusions, no viral surface tubules were recovered. Treatment with the detergent Nonidet-P40 followed by 2-mercaptoethanol disrupted virions without allowing surface tubules to be recovered. Disruption of lipid inclusions by ultrasonic sound or manual grinding of chorioallantoic membranes produced free virions but only small numbers of tubules. These results indicate that surface tubules can be recovered, but that the lipid nature of cytoplasmic inclusions interferes with procedures commonly used in tubule purification. PMID- 6266393 TI - Olfactory discrimination of lithium chloride by the coyote (Canis latrans). PMID- 6266392 TI - Sequential changes in the number of surface immunoglobulin-bearing B lymphocytes in infectious bursal disease virus-infected chickens. AB - Variations of B lymphocytes bearing surface immunoglobulin (SIg) M [SIg(M)] and G [SIg(G)] were studied in the spleen and peripheral blood of chickens infected with infectious bursal disease virus (IBDV). The proportion of SIg-bearing B lymphocytes and SIg(M)- and SIg(G)-bearing B cells in chickens infected at one day of age decreased from 1 week postinfection (p.i.) onward and was significantly lower at 8 weeks p.i. In chickens infected at 4 weeks, the percentage of SIg-bearing B cells decreased severely during the first 2 weeks p.i. The decrease of SIg(M)-bearing B cells preceded that of SIg (G)-bearing B cells: the lowest percentage of SIg(M)-bearing B cells has observed 2 to 3 days p.i., and that of SIg(G)-bearing B cells was seen 4 days p.i. The results suggest that SIg(M)-bearing B cells are the major target for IBDV infection. PMID- 6266394 TI - Experimental studies on genital herpetic infection in mice. AB - Female ICR mice were infected with HSV-1 and HSV-2 by inserting a cotton pellet soaked in viral solution (10(7-8) PFU/m1) into the vagina. The appearance of giant cells and formation of intranuclear inclusions were detected in the epithelial layer of the uterus 24 h after intravaginal inoculation. These histopathological changes were pronounced 3 to 4 days after virus inoculation and then gradually disappeared in the next few days. Results of fluorescent antibody studies on the appearance of viral antigens in infected uterine tissues and results of viral infectivity titrations of emulsified samples of infected uteri coincided well with the histopathological observations on the general course of virus infection. The degree of histopathological involvement caused by HSV-1 was somewhat less than that caused by HSV-2, and the laboratory strains of HSV-1 so far examined (HF and Miyama) were found to be especially weakly pathogenic. PMID- 6266395 TI - A detergent-soluble extract of virus-infected cells free from infectious virus protects mice from lethal herpes simplex virus infection. AB - Lethal infection with herpes simplex virus types 1 (HSV-1) and 2 was effectively prevented by previous immunization with a detergent-soluble extract (DSE) of virus-infected cells free from infectious virus without any adjuvant. This protective immunity seemed to last for at least one month. Neutralizing antibodies were elicited in mice immunized with DSE, but at a lower level than in animals immunized with live or killed virus. DSE did not protect athymic nude mice from death by HSV-1 infection, suggesting that a T cell-mediated immune response plays a major role in the protection. PMID- 6266396 TI - Evidence that arginine vasotocin inhibits human chorionic gonadotropin and cyclic adenosine 3',5' monophosphate stimulated ovarian steroidogenesis. PMID- 6266397 TI - Phase transitions identified in the lipid envelope of Friend murine leukemia virus. PMID- 6266398 TI - Soluble and active renal Na, K-ATPase with maximum protein molecular mass 170,000 +/- 9,000 daltons; formation of larger units by secondary aggregation. PMID- 6266399 TI - On the stoichiometry of oxygen metabolism in polymorphonuclear leukocytes. PMID- 6266401 TI - Epidermal growth factor stimulates monovalent cation transport in isolated rat hepatocytes. PMID- 6266400 TI - Nucleotide sequence of genes coding for dicyclohexylcarbodiimide-binding protein and the alpha subunit of proton-translocating ATPase of Escherichia coli. PMID- 6266402 TI - Second derivative spectroscopic assay of cytochrome P-450 of yeast cells. Resolution of cytochrome a3. PMID- 6266403 TI - Inhibition of angiotensin converting enzyme of rat brain with bradykinin and its fragments. PMID- 6266404 TI - Short term effects of triiodothyronine on rat heart adrenoceptors. PMID- 6266406 TI - Effect of novobiocin on DNA synthesis and structure in human lymphoblastoid cells. PMID- 6266405 TI - A possible role of stimulus-enhanced phosphatidylinositol turnover: calcium sparing effect of diacylglycerol in inducing phase separation of phosphatidyl choline/phosphatidylserine mixtures. PMID- 6266407 TI - Phorbol ester stimulation of Na influx and Na-K pump activity in Swiss 3T3 cells. PMID- 6266408 TI - Inhibitors of poly(ADP-ribose) polymerase enhance unscheduled DNA synthesis in human peripheral lymphocytes. PMID- 6266376 TI - [Surgery of the nerves of the neck, nose, and ear region (except Nn. stato acusticus and olfactorius) (author's transl)]. PMID- 6266409 TI - Nephrogenous cyclic AMP in streptozotocin-induced diabetic rat. PMID- 6266410 TI - Phosphorylation of lens membrane: identification of the catalytic subunit of Na+, K+-ATPase. PMID- 6266412 TI - Specific low density lipoprotein receptors in pig Leydig cells. Role of this lipoprotein in cultured Leydig cells steroidogenesis. PMID- 6266411 TI - Hormonal regulation of serine dehydratase activity in primary cultures of adult rat hepatocytes. PMID- 6266413 TI - Involvement of the proton electrochemical gradient in genetic transformation in Escherichia coli. PMID- 6266414 TI - Isolation of recombinant plasmids containing structural gene sequences for rat seminal vesicle secretory proteins IV and V. PMID- 6266416 TI - Interaction of CDP-diglyceride spin-label with Escherichia coli B membrane fractions and its relationship with phospholipid synthesis. PMID- 6266415 TI - Serum-coated zymosan stimulates the synthesis of leukotriene B4 in human polymorphonuclear leukocytes. Inhibition by cyclic AMP. PMID- 6266417 TI - Energy of the low-lying excited levels for some reduced [4Fe-4S] ferredoxins, from the relaxation broadening of the E.P.R. signals. PMID- 6266418 TI - Chemotactic factors activate differentiable permeation pathways for sodium and calcium in rabbit neutrophils. Effect of amiloride. PMID- 6266419 TI - Evidence that a quinone may be required for the production of superoxide and hydrogen peroxide in neutrophils. PMID- 6266420 TI - "Antibodies raised against beta-adrenergic receptors stimulate adenylate cyclase". PMID- 6266421 TI - Lack of correlation between plasminogen activator production and the continous expression of the transformed phenotype of chicken and mammalian cells as shown with S-adenosyl homocysteine analogues. PMID- 6266422 TI - Ubisemiquinone radicals from the cytochrome b-c1 complex of the mitochondrial electron transport chain--demonstration of QP-S radical formation. PMID- 6266423 TI - Regulation of the basal and cyclic AMP-stimulated rates of glycogen synthesis in Escherichia coli by an intermediate of purine biosynthesis. PMID- 6266424 TI - Variable ATPase composition of human tumor plasma membranes. PMID- 6266425 TI - Effects on fluorine analogs of norepinephrine on stimulation of cyclic adenosine 3',5'-monophosphate and binding to beta-adrenergic receptors in intact pinealocytes. PMID- 6266426 TI - Acute pseudogout: "crystal shedding" or acute crystallization? PMID- 6266427 TI - [Chemotherapy of transplanted neurogenic tumors in the rat (author's transl)]. AB - 1. After s.c. and intracerebral (i.c.) inoculation, 4 neurogenic tumors of the rat (3 malignant neurinomas, 1 polymorphcellular glioma) revealed an altogether weak response towards a monotherapy with 1,3-bis(2-chloroethyl)-1 nitrosourea(BCNU), 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), 1-(2 chloroethyl)-3-(4-Methylcyclohexyl)-1-nitro sourea (MeCCNU), 1-(2-hydroxyethyl)-3 (2-chloroethyl)-3-nitrosourea (OH-ethyl-CCNU), 2-[3-(2-chloroethyl)-3 nitrosoureidol]-D-glucopyranose (chlorozotocin), 5-(3,3-dimethyl-1-triazeno) imidazol-4-carboxamide (DTIC). Cyclophosphamide (CPA) which was investigated for comparison showed the greatest therapeutic activity; in an equitoxic dosage (less than or equal to LD10), in all 4 s.c. tumors, partial or complete regression were effected only by CPA. 2. If the passage number increases, the response of transplanted neurogenic rat tumors to monochemotherapy can both increase and decrease. 3. In the monotherapy of 3 malignant neurinomas we were unable, on the whole, to observe a higher sensitivity after s.c. inoculation as compared with an i.c. inoculation of the tumor, despite a varying effectiveness of the single substances. 4. In the monotherapy of the polymorphcellular glioma a better response of the i.c. inoculated tumor was recognizable compared to the s.c. inoculated tumor. 5. A combination chemotherapy of a malignant neurinoma after s.c. and i.c. inoculation with vincristine, CPA, OH-ethyl-CNU and MeCcNU yielded a significant increase in life-span of animals with i.c. tumor, whereas s.c. tumors showed no significant growth inhibition. y. Transplanted neurogenic tumors of the rat could serve at less sensitive models for the investigation of new nitrosoureas. PMID- 6266429 TI - Determination of pipecurium bromide, a new non-depolarizing neuromuscular blocking agent, in human serum. AB - A method for the determination of 2 beta, 16 beta-bis (4'dimethyl-1'-piperazino) 3a, 17 beta-diacetoxy-5 alpha-androstane is described. After deproteinization a pipecurium bromide Rose Bengal complex is formed and extracted with chloroform from a mildly basic medium. The amount of pipecurium bromide is proportional to the amount of Rose Bengal in the complex, and the quantity of the latter can easily be determined by measuring its iodine content. The method is sufficiently sensitive to be used for the analysis of human serum. PMID- 6266428 TI - Effect of cyproterone acetate and its metabolites on the adrenal function in man, rhesus monkey and rat. AB - The effect of oral administration of 17 alpha-acetoxy-6-chloro-1,2 alpha methylene-4,6]pregnadiene-3,20-dione (cyproterone acetate, Androcur) on the adrenal function in male hypersexual subjects and in female rhesus monkey was investigated on the basis of cortisol and ACTH levels in serum or plasma and excretion of cortisol and 17-ketosteroids. In addition, cyproterone acetate and its main metabolite alcohol of the main metabolite were characterized for treatment of male hypersexual subjects and female rhesus monkeys did not reveal any signs of adrenal suppression. Cyproterone acetate and its metabolites gave on indication of any appreciable anti-inflammatory effect in the adjuvant edema test in rats. However, there was a general increase in the level of blood glucose and liver glycogen as well as a reduction in body weight and organ weight (spleen, thymus and adrenal) in rats, in which 15 beta-hydroxy cyproterone was slightly more active with the exception of adrenal weight tests. It can be concluded that adult man and rhesus monkey are much less sensitive, is so at all, to some corticosteroid-like activities of cyproterone acetate and its main metabolites than the rat. PMID- 6266430 TI - Antibacterial activity of moxalactam (LY-127935) compared with cefotaxime and other beta-lactam antibiotics against clinical isolates of enterobacteriacea and non-fermenters. AB - The in vitro activity of moxalactam, a new semisynthetic 1-oxa-beta-lactam, was compared to those cefotaxime, cefuroxime, cephalothin, piperacillin and tobramycin against more than 500 clinical isolates of Enterobacteriaceae and non fermenters. The geometric mean MIC against 450 Enterobacteriaceae in microgram/ml was 0.09 for moxalactam, 0.08 for cefotaxime, 5.3 for cefuroxime, 22.9 for cephalothin, 3.5 for piperacillin and 0.72 for tobramycin. The geometric mean MIC in microgram/ml against 60 P. aeruginosa strains was 12.7 for moxalactam, 22.9 for cefotaxime, 6.8 for piperacillin, 1.5 for tobramycin and 2.9 for cefsoludin. The minimum inhibitory and the bactericidal concentrations of moxalactam were almost the same in most species. The effect of the inoculum on the bactericidal concentration was slight, between 10(3) and 10(7) CFU/ml for the E. coli and the Klebsiella strains. In isolates of S. marcescens and P. aeruginosa the bactericidal concentrations increased by 4 to 5 log2 and in isolates of P. mirabilis the increased by 9 log2 with the largest inoculum. PMID- 6266431 TI - Studies of human plate alpha-granule release in vivo. PMID- 6266432 TI - Leukotriene B4 is a potent and stereospecific stimulator of neutrophil chemotaxis and adherence. AB - We studied the effects of leukotrienes on in vitro functions of neutrophil polymorphonuclear (PMN) granulocytes. Leukotriene B4 (LTB4) evoked a stimulated and directed migration of neutrophils under agarose with an optimum concentration of 10(-6)M, whereas two nonenzymatically formed isomers (compounds I and II) induced this response at 10(-5)M. Leukotriene C4 (LTC4) and 5-hydroxyeicosate traenoic acid (5-HETE) did not affect this PMN migration. At the same optimum concentrations, LTB4 and compounds I and II augmented PMN adherence to nylon fibers. The chemotactic and adherence responses were of the same magnitude as with formal-Met-Leu-Phe (fMLP) at 10(-7)M. None of the leukotrienes influenced the spontaneous or phagocytosis-associated chemiluminescence or the ability to kill Staphylococcus aures. The cyclooxygenase inhibitor, indomethacin, inhibited only partly the fMLP-induced migration at high concentrations and stimulated migration at 2.5 x 10(-7)M, suggesting that arachidonic acid was then mainly metabolized by the lipoxygenase pathways. The lipoxygenase and cyclooxygenase inhibitor, eicosatetraynoic acid, inhibited both spontaneous and stimulated migration at greater or equal to 2.5 x 10(-5)M, but not at lower concentrations. Thus, since LTB4, and to a lesser degree compounds I and II, stimulated migration and adhesion, it is suggested that these mediators could be of importance for the emigration of neutrophils from blood vessels to areas of inflammation. PMID- 6266433 TI - The role of opioid peptides in memory and learning. AB - Evidence is discussed which points to the existence of a physiologic amnesic mechanism mediated by beta-endorphin and perhaps by other opioid peptides as well. This mechanism is triggered by various forms of training and by either painful or painless stimulation. It may operate through the inhibition of central dopaminergic and beta-adrenergic systems that modulate the memory consolidation process. This amnesic mechanism in unrelated to the regulation of pain perception, and operates at opioid peptide levels several orders of magnitude below those that are needed to cause analgesia or other effects. In addition, shuttle avoidance and habituation learning seem to be dependent on a state induced by the release of beta-endorphin. It is possible that this may be related to the amnesic properties of this substance. Therefore, it appears that the endogenous opioid peptides may exert their primary function in the modulation of memory processes. PMID- 6266434 TI - [Modifications of enzyme activities in rat liver plasma membrane after carbon tetrachloride poisoning]. AB - Adenylate Cyclase activity is increased in the liver of animals treated with CCl4 (250 ul/100g body wt.) after 30 min. The maximum increase is observed 2 hours after administration of the hepatotoxin. Whereas, 3',5' nucleotidephosphodiesterase decreases significantly throughout all the experiments. Our results present evidence that there is relationship between Adenylate Cyclase and Phosphodiesterase activity and suggest that intracellular calcium ion may mediate a regulation of the synthesis and degradation of cyclic nucleotides. It is difficult to determine the exact role Ca2+ plays in regulating these two opposing reactions. Thus, in the near future the work in this laboratory will be to define carefully the effects of the CCl4 on ions on these two systems. PMID- 6266435 TI - [Sequential change of cAMP concentration in cerebrospinal fluid after cerebrovascular accident--a clinical investigation (author's transl)]. PMID- 6266437 TI - [Endocrine diagnosis of pituitary adenomas (author's transl)]. PMID- 6266436 TI - [Subclinical pituitary microadenoma (author's transl)]. PMID- 6266438 TI - [Neuroradiological diagnosis of microadenoma (author's transl)]. PMID- 6266439 TI - [Rhinoseptoplastic transsphenoidal microsurgery in the treatment of functioning pituitary adenomas: Results of 100 consecutive cases (author's transl)]. PMID- 6266440 TI - [Surgical treatment of functioning adenoma--evaluation of the results of Hardy method (sublabial rhinoseptal transsphenoidal approach) in cases of functioning adenomas (author's transl)]. PMID- 6266441 TI - [Pathology of functioning pituitary adenomas with emphasis on the immunohistochemical classification (author's transl)]. PMID- 6266442 TI - [Lafora-like neuronal inclusions in the nucleus tegmentalis pedunculopontinus- their relation of aging (author's transl)]. AB - At routine postmortem examinations, peculiar basophilic inclusion bodies were often encountered in nerve cells of the nucleus tegmentalis pendunculopontinus in the lower midbrain. Morphology and histochemistry of these inclusions were most similar to Lafora bodies commonly seen in Lafora type myoclonus epilepsy. Incidence and distribution of such Lafora-like bodies were examined in transverse sections through the lower midbrain of 38 patients selected at random who did not have storage or degenerative diseases. In neurons of 14 out of these 38 cases, at least one Lafora-like body was found. Their distribution was restricted to the nucleus tegmentalis pedunculopontinus. Almost every body occupied the neuronal perikarya to various degrees or they were also seen in the neuropil. Clinical data and autopsy findings revealed age-dependence of these bodies and also probable correlation to cerebral infarction: 5 or the 14 positive cases had old cerebral infarcts. In addition to Lafora type myoclonus epilepsy and rare instance of certain degenerative diseases, also aging may induce formation of Lafora-like bodies, though regionally restricted, in neurons. PMID- 6266443 TI - [Cranial hemihypertrophy in Klippel-Trenaunay syndrome (author's transl)]. AB - Klippel-Trenaunay Syndrome with hemicranial hypertrophy and macrodactyly is reported. The patient was a 3-year-old Japanese woman with an extensive nevus flammeus which extended over the right side of the neck, axilla, upper arm, and leg. Her right extremities were longer and thicker than left, and showed apparent macrodactyly in the right hand. Her skin of right side body was irregular, rough surface and was pigmented prominently. Hyperthermia was present in the hypertrophic limbs, but hyperhidrosis was none. She had moderate mental retardation, delayed speech. Her hemicranial hypertrophy (same side as hypertrophic limbs) was examined by CT scan. Her right lateral ventricle was dilatated and cortical sulci was well demonstrated. Her right hemicranial volume was enlarged but rt-cerebral hemisphere was atrophic, and her infratentorial structures were symmetrical. Presented case, Klippel-Trenaunay Syndrome with hemicranial hypertrophy, suggested the embryological theory affecting on trilaminar disc in embryonal stage as the genesis of this rare syndrome. PMID- 6266444 TI - Localised acneiform eruption following X-ray irradiation. PMID- 6266445 TI - Lung cancer, immune status, histopathology and smoking. Is oat cell carcinoma lymphodependent? AB - Life table analysis and partial correlation analysis have been used to examine the importance and interaction of those factors reported to affect prognosis in lung cancer, in a group of men taking part in a recent trial (Anthony et al. 1978). In patients with squamous carcinoma the lymphocyte count at diagnosis was a genuine correlate of survival, those with higher counts living longer. Patients who had smoked more heavily were younger when their tumours were found, had better differentiated carcinomas and longer survival. Those with poorer differentiation had weaker skin test reactivity but the expected shorter survival was seen only when controls for symptom pattern history and resectability were applied. These data could be explained by control of tumour extension by cell mediated immunity, earlier induction of better differentiated tumours in heavier smokers, more insidious onset of symptoms in those with better differentiated tumours and the depression of cell-mediated immunity by poorly differentiated tumours. In contrast, the longer survivors among patients with oat cell carcinoma had lower lymphocyte and monocyte counts at the time of diagnosis. Lymphocyte and monocyte counts contributed independently to survival in keeping with oat cell carcinoma being lymphodependent (Prehn 1977) and resistant to immune cytolysis. PMID- 6266446 TI - Circulating IgE levels in patients with bronchial carcinoma. AB - Serum IgE measurements in 107 patients with bronchial carcinoma revealed statistically significant elevations when compared to a control population. Serum IgE elevation was seen in 21.5% of the sample (23 of 107) and in all histological types at all clinical stages of the disease. It appears to occur early in the disease or possibly before the development of the carcinoma. PMID- 6266447 TI - Peripheral neuropathy and plasma cell neoplasias: a report of 10 cases. AB - Ten patients with peripheral polyneuropathy associated with plasma cell neoplasias are reported. Progressive sensorimotor polyneuropathy was the presenting complaint in all patients. CSF protein concentration was elevated in most patients. The electrophysiological and pathological changes were consistent with a primary segmentary demyelinating disease. All patients were male and younger than the average patient with myeloma. None presented with high tumour mass or overt multiple myeloma. Six were affected with single or multiple plasmacytomas with osteolytic lesions. Unusual haematological features such as polycythaemia, thrombocytosis and lymphadenopathy were often combined with the polyneuropathy. Skin hyperpigmentation, gynaecomastia and diabetes mellitus were noted in some patients. Complete recovery of the polyneuropathy was observed in some patients after either cyclophosphamide and corticosteroid therapy or radiotherapy of localized plasmacytoma, suggesting a direct relationship between the plasmacytic proliferation and the neuropathy. The nature of the postulated factor produced by the plasma cells and responsible for nerve injury is discussed and the importance of a careful search for plasma cell proliferation in men with obscure polyneuropathies is outlined. PMID- 6266448 TI - Chorioretinal biopsy in a patient with leukaemia. PMID- 6266449 TI - Hydrolysis of the phytate of wheat flour during breadmaking. AB - 1. Differences in the extent of breakdown of phytate in wholemeal and white flours prepared from three wheats when the flours were made into bread using the three main UK commercial breadmaking processes were investigated. 2. The extent of breakdown (31-46% for wholemeal breads, 88-99% for white breads) was not proportional to the relative processing times involved (1-4 h). The importance of destruction of phytate in the oven is stressed. 3. The phytase (myo-inositol hexaphosphate phosphohydrolase, EC 3. 1. 3.8) activities of the wholemeal flours and the yeast were determined. Re-examination of some information in the literature enabled the relative importance of these activities, and of the various stages of breadmaking, in determining the extent of hydrolysis of phytate to be assessed. 4. Average values for the molar ratio, phytate: zinc, of 22:1 and 0.8:1 were calculated for wholemeal and white breads respectively. The nutritional significance of these results is discussed. PMID- 6266450 TI - Availability to pigs of amino acids in cereal grains. 1. Endogenous levels of amino acids in ileal digesta and faeces of pigs given cereal diets. AB - 1. Endogenous levels of amino acids in ileal digesta were determined as the output from pigs given protein-free diets and by extrapolation to zero intake of linear regressions of ileal amino acid output v. dietary amino acid intake. The protein-free diets included 0 or 50 g cellulose/kg and extrapolations were made from two series of four diets which contained graded levels of wheat or barley as the only source of protein. Within each series, dietary fibre level (mg/g) was maintained at approximately 140 or 190 neutral-detergent fibre (NDF) respectively. Endogenous amino acid levels in faeces were also determined. 2. Endogenous amino acid output in faeces was linearly related to dietary fibre level; endogenous ileal output increased with dietary fibre up to approximately 100 mg NDF/g, after which endogenous output no longer increased. 3. The amino acid composition of endogenous ileal protein varied little among levels of output and among different experiments. The composition appears to be determined by the predominance of mucin protein, the slow absorption of some acids and the methods commonly used to measure output. The very high levels of proline and glycine in ileal digesta seemed characteristic only of protein-free and low-protein diets. 4. The amino acid composition of endogenous faecal protein also varied little among different estimates, but was considerably different from that of endogenous ileal protein. Furthermore, the similarity of bacterial and faecal proteins suggested that much of the endogenous faecal protein was of bacterial origin. PMID- 6266451 TI - The digestive capacity of the caecum-colon and the value of the nitrogen absorbed from the hind gut for protein synthesis in pigs. AB - 1. The aim of the investigation was to study the effects of lysine, methionine, crude protein, a complete balanced diet, maize starch and potato starch infused continuously into the caecum on the digestibility of the nutrients, urinary nitrogen excretion and N balance in the presence of a normal or a depressed (modified) microflora. 2. The effects of the the infused nutrients on digestibility differed when diets supplemented with antibiotics were compared with unsupplemented diets. 3. Infused lysine improved the digestibility of crude protein (0.004/g lysine), crude fibre (0.01/g lysine), gross energy (0.003/g lysine) and lysine (0.03/g lysine) when the diets were not supplemented with antibiotics. 4. Infused lysine, methionine and crude protein seemed to be of very little value for protein synthesis in the pigs, as the effects on N balance, although positive, were very small. 5. Despite the fact that a part of the infused lysine passed through the caecum-colon and into the faeces intact, the effect of N balance was negligible, indicating that the ability to absorb amino acids through the gut wall in the caecum-colon was very poor. 6. Crude protein, a complete balanced diet, maize starch and potato starch infused into the caecum were digested almost as well as if they had been given orally, thus demonstrating the large digestive capacity of the caecum-colon. PMID- 6266452 TI - Apparent hydrogen bonding by strongly immobilized spin-labels. AB - The hyperfine separations of nitroxide spin-labels which are tightly bound within hemoglobin exhibit a substantial temperature dependence even when the hemoglobin is immobilized by freezing or precipitation. It is shown that NO.--HX hydrogen bond formation by the spin-label within its binding site is a good explanation for the observed temperature dependence. Comparative studies using different hemoglobin derivatives and two different spin-labels suggest that the HX group may be some element of the protein matrix and that this hydrogen bond may be a factor in the stabilization of the label within its binding site. The hyperfine separation of a fatty acid spin probe incorporated into aqueous bilayer dispersons of dipalmitoylphosphatidylcholine also exhibits a temperature dependence at low temperature which is qualitatively similar to that of the spin labeled hemoglobin systems. Saturation transfer electron paramagnetic resonance measurements indicate that label motion is not the source of this temperature dependence. A hydrogen-bond equilibrium between water molecules and the nitroxide NO. group appears to be a plausible source of the temperature-dependent hyperfine separation in the lipid bilayer system. Small amplitude torsional oscillation or librational motion by the nitroxide may also produce additional changes in the hyperfine separation which are difficult to distinguish from hydrogen-bonding effects under some circumstances. The apparent hydrogen-bond equilibrium exhibits a strong thermal and environmental dependence which may be of importance in a number of biophysical spin-label measurements. PMID- 6266453 TI - Preparation of photoreactive derivatives of glutathione and [9-(2 mercaptotryptophan)]corticotropin by selective modification of the sulfhydryl group. AB - The photoreactive arylsulfenyl chlorides 2-nitro-4-azidophenylsulfenyl chloride (2,4-NAPS-Cl) and 2-nitro-5-azidophenylsulfenyl chloride (2,5-NAPS-Cl) have been used for the selective modification of thiol groups in glutathione and [Trp(SH)9]corticotropin (ACTH). Both reagents reacted rapidly with both types of thiol groups to form unsymmetrical disulfides. The photoreactive derivatives of glutathione and [Trp(SH)9]ACTH were stable to neutral and acidic conditions but were readily cleaved above pH 9 and by beta-mercaptoethanol. Photolysis of the NAPS derivatives of [Trp(SH)9]-ACTH at neutral pH resulted in the formation of covalently liked polymers and dimers which yielded monomer upon treatment with beta-mercaptoethanol. Analysis of the amino acid composition of acid hydrolysates of photolysed monomeric and dimeric products indicated a decrease in proline, valine, tyrosine, and phenylalanine. PMID- 6266454 TI - Identification of the corticotropin binding domain of bovine serum albumin by photoaffinity labeling. AB - The interaction of the pituitary hormone corticotropin (ACTH) with bovine serum albumin (BSA) was investigated by photoaffinity labeling with 2-nitro-4-azido phenylsulfenyl (2,4-NAPS) derivatives of aCTH and [Trp-(SH)9]ACTH. Nearly 30 mol % of tritiated [2,4-NAPS-Trp9]ACTH was covalently bound to BSA at a molar ratio of hormone:BSA of 1.33. The [2,4-NAPS-Trp9] [3H]ACTH-BSA complex was isolated, and the CNBr fragments of the complex were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The radioactivity was predominantly associated with the amino-terminal CNBr fragment corresponding to residues 1-183 in BSA. This result was confirmed by studies of the inhibition of covalent labeling of BSA by photoreactive ACTH. 8-Anilinonaphthalenesulfonic acid which binds to the amino-terminal domain of BSA strongly inhibited the photolabeling of BSA by [2,4-NAPS-Trp9][3H]ACTH. Palmitate and progesterone, known to bind to the carboxy-terminal domains of BSA, did not inhibit the incorporation of [2,4]NAPS Trp9][3H]ACTH into BSA. The removal of ACTH from the covalent complexes was also investigated. The release of ACTH from the [2,4]NAPSS-Trp9]ACTH--BSA complex by treatment with beta-mercaptoethanol was complete in 6 h, but only 80% of ACTH was released from [2,4]NAPS-Trp9]ACTH--BSA under these conditions. PMID- 6266455 TI - Kinetics of hydrogen ion diffusion across phospholipid vesicle membranes. AB - The membrane-impermeant, pH-sensitive fluorescence probe 8-hydroxy-1,3,6 pyrenetrisulfonate can be entrapped within the internal aqueous compartment of unilamellar phospholipid vesicles, where it serves as a reliable indicator of internal aqueous hydrogen ion concentration [Clement, N. R., & Gould, J. M. (1981) Biochemistry 20, 1534-1539]. When the external (medium) pH of a suspension of soybean phospholipid vesicles was rapidly changed from 8.2 to 6.65, the rate of subsequent H+ influx into the vesicles, measured as the change in pyranine fluorescence, was limited (in KCl media) by the rate of charge-compensating counterion redistributions. The half-time for the pyranine fluorescence change (corresponding to an internal pH change from 8.2 to 7.43), which was several minutes in the absence of valinomycin, could be decreased to approximately 300 ms, but not further, by the K+ ionophore valinomycin. Proton ionophores such as gramicidin or bis(hexafluoroacetonyl)acetone (1799), on the other hand, decreased the time required for transmembrane H+ equilibration to less than 1 ms. These findings indicate that the intrinsic permeability of unilamellar vesicle membranes to hydrogen ions is surprisingly high and much greater than the observed permeabilities of other small ions. PMID- 6266456 TI - Effects of procollagen peptides on the translation of type II collagen messenger ribonucleic acid and on collagen biosynthesis in chondrocytes. AB - Type II procollagen messenger ribonucleic acid (mRNA) was isolated from chick sternum and rat chondrosarcoma cells and translated in a reticulocyte lysate cell free system. A high molecular weight band was identified as type II procollagen by gel electrophoresis, collagenase digestion, and specific immunoprecipitation. The translation of type II mRNA was specifically inhibited by addition of type I procollagen amino-terminal extension peptide. When this peptide was added to the media of cultured fetal calf chondrocytes, chick sternal chondrocytes, or chick tendon fibroblasts, no inhibition of collagen synthesis was evident. These data suggest a general regulation of collagen biosynthesis by these peptides in the cell-free translation system. However, as indicated by the cell culture experiments, cellular characteristics and evolutionary divergence of animal species seem to restrict the effect of the peptides. PMID- 6266457 TI - Single-strand deoxyribonucleic acid binding protein from rat liver changes the helical structure of deoxyribonucleic acid. AB - Incubation of rat liver single-strand DNA binding protein S25 with covalently closed relaxed SV40 DNA in the presence of rat liver topoisomerase I induced a decrease in the linking number LK of DNA, so that it appeared negatively supertwisted after removal of the protein. delta LK was found to be a linear function of protein to DNA ratio and reached a plateau corresponding to about 15 superhelical turns. The same result was obtained when S25 was incubated with form I or form Ir before addition of topoisomerase I or when SV40 was replaced by PM2 DNA. The observed reduction in the linking number of DNA when it is closed in the presence of rat liver protein S25 can be explained either by supercoiling of DNA induced by S25 or by detorsion or unwinding of DNA. PMID- 6266458 TI - Poly(adenosine diphosphoribose) synthesis in ultraviolet-irradiated xeroderma pigmentosum cells reconstituted with Micrococcus luteus UV endonuclease. AB - Synthesis of DNA and poly(adenosine diphosphoribose) [poly(ADPR)] was examined in permeabilized xeroderma pigmentosum lymphoblasts (XP3BE) before and after UV irradiation and in the presence and absence of Micrococcus luteus UV endonuclease. M. luteus UV endonuclease had no effect on the level of DNA or poly(ADPR) synthesis in control, unirradiated cells. UV irradiation caused a decrease in replicative DNA synthesis without any significant change in poly(ADPR) synthesis. In UV-irradiated cells treated with M. luteus UV endonuclease, DNA synthesis was restored to a level slightly greater than in the unirradiated control cells, and poly(ADPR) synthesis increased by 2- to 4-fold. Time--course studies showed that the UV endonuclease dependent poly(ADPR) synthesis preceded the endonuclease-dependent DNA synthesis. Inhibition of endonuclease-dependent poly(ADPR) synthesis with 3-aminobenzamide, 5 methylnicotinamide, or theophylline produced a partial inhibition of the endonuclease-dependent DNA synthesis. Conversely, inhibition of the endonuclease dependent DNA synthesis with dideoxythymidine triphosphate, phosphonoacetic acid, or aphidicolin had no effect on the endonuclease-dependent poly(ADPR) synthesis. These studies show that stimulation of poly(ADPR) synthesis in UV-irradiated cells occurs subsequent to the DNA strand breaks created by the specific action of the UV endonuclease on UV-irradiated DNA. The effect of the inhibitors of poly(ADPR) synthesis in UV-irradiated cells indicates that the endonuclease stimulated DNA synthesis is dependent in part on the prior synthesis of poly(ADPR). PMID- 6266459 TI - Lipid composition and (Na+ + K+)-ATPase activity in rat lens during triparanol induced cataract formation. AB - The development of triparanol cataracts in rats is accompanied by the loss of lens (Na+ + K+)-ATPase activity and by alteration in the lens content and composition of phospholipids, sterols and phospholipid acyl groups. The lipid changes occur along the same time course as the loss of (NA+ + K+)-ATPase activity. Triparanol feeding produces a decrease in lens phospholipid content. The percentage contents of phosphatidylcholine and phosphatidyl-serine decrease while the content of sphingomyelin substantially increases. The amounts of oleic acid in lens phospholipids decrease while stearic and palmitic acids increase; however, these changes are relatively small. Sterol content is also decreased while the percentage content of desmosterol increases markedly. Feeding of the cataractogenic agents galactose and diazacholesterol also alters the lens lipid compositions and (Na+ + K+)-ATPase activity. A loss of phosphatidylserine is the only change in lipid properties which always accompanies a loss of the enzyme activity. The possible relationships between the lens content of phosphatidylserine, (Na+ + K+)-ATPase activity and the mechanism of triparanol induced cataract formation are discussed. PMID- 6266460 TI - Immunological evidence that plasma-membrane 5'-nucleotidase is a transmembrane protein. AB - Antibodies inhibiting specifically plasma membrane-bound 5'nucleotidase were used to determine the disposition of the enzyme in various lymphoma cell lines. Fluorescent Fab fragments of the inhibiting antibodies bound to MF2s and MOPC 173 plasmacytoma cells, whereas no fluorescence was observed with P 1798 thymoma cells in which the enzyme was absent. The relative potency of the antiserum in inhibiting the enzyme in right-side-out and inside-out plasma membrane vesicles prepared from the above cell lines indicated that various group of antigenic determinants were present. One group of antigenic determinants was present at the external face of the cell, and a second was associated with the inner surface of the membrane. A third group of antigenic determinants was located in the vicinity of the active site of the enzyme and it is the group that varied in the various plasmacytoma cells studied. The results are interpreted as immunological evidence that 5'nucleotidase is a transmembrane glycoprotein. PMID- 6266461 TI - Electrokinetic properties of (Na+, K+)-ATPase vesicles as studied by laser Doppler spectroscopy. AB - The technique of laser Doppler electrophoresis was applied for the study of the surface charge properties of (NA+, K+)-ATPase containing microsomal vesicles derived from guinea-pig kidney. The influence of pH, the screening and binding of uni- and divalent cations and the binding of ATP show: (1) one net negative charge per protein unit with a pK = 3.9; (2) deviation from the Debye relation between surface potential and ionic strength for univalent cations, with no difference in the effect of Na+ and K+; (3) Mg2+ binds with an association constant of Ka = 1.1. 10(2) M-1 while ATP binds with an apparent Ka = 1.1.10(4) M 1 for 1 mM NaCl, 0.2 mM KCI, 0.1 mM MgCl2, 0.1 mM Tris-HCl2, 0.1 mM Tris-HCl (pH 7.3). The binding is weaker at higher Mg2+ concentrations. There is no ATP binding in the absence of Mg2+. In addition, the average vesicle size derived from the linewidth of the quasielastic light scattering spectrum is 203.7 +/- 15.2 nm. In the presence of ATP a reduction in size is observed. PMID- 6266462 TI - Hydrofluoric and nitric acid transport through lipid bilayer membranes. AB - Hydrofluoric and nitric acid transport through lipid bilayer membranes were studied by a combination of electrical conductance and pH electrode techniques. Transport occurs primarily by nonionic diffusion of molecular HF and HNO3. Membrane permeabilities to HF and HNO3 ranged from 10(-4) to 10(-3) cm . s-1, five to seven orders of magnitude higher than the permeabilities to NO-3, F- and H+. Our results are consistent with the hypothesis that F- transport through biological membranes occurs mainly by nonionic diffusion of HF. Our results also suggest that of the two principal components of 'acid rain', HNO3 may be more toxic than H2SO4. PMID- 6266463 TI - Temperature effects on cation affinities of the (Na+, K+)-ATPase of mammalian brain. AB - Effects of temperature on the Na+-dependent ADP-ATP exchange and the p nitrophenylphosphatase reactions catalysed by (Na+, K+)-ATPase were examined. Apparent Mg2+ affinity decreased with decreasing temperature. Arrhenius plots of p-nitrophenylphosphatase in the presence of Na+ and ATP had discontinuities similar to those previously reported for (Na+ + K+)-ATPase, while those of p nitrophenylphosphatase measured without Na+ or ATP did not. The apparent activation energy for p-nitrophenylphosphatase was a function of the physical characteristics of the cation acting at the K+ site. PMID- 6266464 TI - Ligand-dependent reactivity of (Na+ + K+)-ATPase with showdomycin. AB - Showdomycin inhibited pig brain (Na+ + K+)-ATPase with pseudo first-order kinetics. The rate of inhibition by showdomycin was examined in the presence of 16 combinations of four ligands, i.e., Na+, K+, Mg2+ and ATP, and was found to depend on the ligands added. Combinations of ligands were divided into five groups in terms of the magnitude of the rate constant; in the order of decreasing rate constants these were: (1) Na+ + Mg2+ + ATP, (2) Mg2+, Mg2+ + K+, K+ and none, (3) Na+ + Mg2+, Na+, K+ + Na+ and Na+ + K+ + Mg2+, (4) Mg2+ + K+ + ATP, K+ + ATP and Mg2+ + ATP, (5) K+ + Na + + ATP, Na+ + ATP, Na+ + K+ + Mg2+ + ATP and ATP. The highest rate was obtained in the presence of Na+, Mg2+ and ATP. The apparent concentrations of Na+, Mg2+ and ATP for half-maximum stimulation of inhibition (KS0.5) were 3 mM, 0.13 mM and 4 MicroM, respectively. The rate was unchanged upon further increase in Na+ concentration from 140 to 1000 mM. The rates of inhibition could be explained on the basis of the enzyme forms present, including E1, E2, ES, E1-P and E2-P, i. e., E2 has higher reactivity with showdomycin than E1, while E2-P has almost the same reactivity as E1-P. We conclude that the reaction of (Na+ + K+)- ATPase proceeds via at least four kinds of enzyme form (E1, E2, E1 . nucleotide and EP), which all have different conformations. PMID- 6266465 TI - Aging of the erythrocyte. IV. Spin-label studies of membrane lipids, proteins and permeability. AB - Spin-label studies demonstrated age-related alterations of the erythrocyte membrane concerning both lipid and protein components. Decrease in fluidity of membrane lipids correlated with decreased membrane permeability to a hydrophobic spin label TEMPO, permeability to a more hydrophilic TEMPOL being less affected. The rigidification of membrane lipids was much more pronounced in whole membranes than in liposomes composed of membrane lipids, suggesting changes in lipid protein interactions as an important factor in the decrease of lipid fluidity in aged red cells. ESR spectra of membrane-bound maleimide spin label evidenced alterations in the state of membrane proteins during cell aging in vivo. PMID- 6266466 TI - Physical properties of phosphatidylcholine-phosphatidylinositol liposomes in relation to a calcium effect. AB - Physical properties of binary mixtures of dipalmitoylphosphatidylcholine and yeast phosphatidylinositol were studied by ESR analysis using TEMPO (2,2,6,6 tetramethylpiperidine-1-oxyl) and lipid spin probes, freeze-fracture electronmicroscopy and particle microelectrophoresis, and they were compared with those of phosphatidylcholine/bovine brain phosphatidylserine mixtures. The phase diagram of the binary mixtures of dipalmitoylphosphatidylcholine and phosphatidylinositol was obtained from the thermal features of TEMPO spectral parameter in the lipid mixtures. The phase diagram provided evidence that these two phospholipids in various combinations were miscible in the crystalline state. The addition of 10 mM Ca2+ slightly shifted the phase diagram upward. TEMPO titration of the binary mixture of dipalmitoylphosphatidylcholine and bovine brain phosphatidylserine revealed that 10 mM Ca2+ caused the complete phase separation of this lipid mixture. Studies of phase separations using phosphatidylcholine spin probe manifested that 10 mM Ca2+ induced almost complete phase separation in egg yolk phosphatidylcholine/bovine brain phosphatidylserine mixtures but only slight phase separation in egg yolk phosphatidylcholine/yeast phosphatidylinositol mixtures. However, some phase changes around the fluidus and the solidus curves were visualized by the freeze-fracture electronmicroscopy. The molecular motion of lipid spin probe was decreased by the addition of Ca2+ in the liposomes containing phosphatidylinositol. The temperature dependence of electrophoretic mobility was also examined in the absence and presence of 1 mM Ca2+. Liposomes of dipalmitoylphosphatidylcholine-phosphatidylinositol (90 : 10, mol/mol) exhibited a clear transition in the thermal features of electrophoretic mobilities. Raising the phosphatidylinositol content up to 25 mol% rendered the transition broad and unclear. The addition of 1 mM Ca2+ decreased the electrophoretic mobility but did not change its general profile of the thermal dependence. These results suggest that the addition of calcium ions induced a small phase change in the binary mixture of phosphatidylcholine and phosphatidylinositol while Ca2+ causes a remarkable phase separation in phosphatidylcholine/phosphatidylserine mixture. The physical role of phosphatidylinositol is discussed related to the formation of diacylglycerol. PMID- 6266467 TI - Haptenic activity of galactosyl ceramide and its topographical distribution on liposomal membranes. I. Effect of cholesterol incorporation. AB - The relation between the immune-reaction of phosphatidylcholine liposomes containing spin-labeled galactosyl ceramide with or without cholesterol and the topographical distribution of the glycolipid in membranes was studied. In egg yolk phosphatidylcholine liposomes, both immune agglutination and antibody binding occurred, irrespectively of the presence of cholesterol, though the motion of the fatty acyl chain of spin-labeled galactosyl ceramide was restricted by cholesterol. In dipalmitoyl phosphatidylcholine liposomes, unlike in egg yolk phosphatidylcholine liposomes, the immune-reaction depended on the cholesterol content. The electron spin resonance (ESR) spectra of spin-labeled galactosyl ceramide in dipalmitoyl phosphatidylcholine liposomes indicated that cholesterol affected the topographical distribution of spin-labeled galactosyl ceramide in the liposomes. Without cholesterol, most of the spin-labeled galactosyl ceramide was clustered on the dipalmitoyl phosphatidylcholine membrane, but with increase of cholesterol, random distribution of hapten on the membrane increased. The cholesterol-dependent change in the topographical distribution of hapten on the membranes was parallel with that of immune reactivity. 'Aggregates' composed solely of galactosyl ceramide did not show any binding activity with antibody. The findings suggest that the recognition of galactosyl ceramide by antibody depended on the topographical distribution of hapten molecules. Phosphatidylcholine and/or cholesterol may play roles as 'spacers' for the proper distribution of 'active' haptens on the membranes. The optimum density of haptens properly distributed on liposomal membranes is discussed. PMID- 6266468 TI - A spin label method for measuring internal volumes in liposomes or cells, applied to Ca-dependent fusion of negatively charged vesicles. AB - A new spin label - broadening agent system for measuring trapped volumes of vesicles or cells is described. The method seems to be more advantageous than existing procedures when volumes of highly negatively charged vesicles are to be determined. The membrane permeable spin label is TEMPONE (2,2,6,6-tetramethyl piperidone-N-oxyl), and the nonpermeable broadening agent is chromium oxalate (K3Cr(C2O4)3). Absolute values for the trapped volumes down to 0.1% in 0.1 ml can be measured with an accuracy of about +/- (1-10%). The method is used to study the final volume of fused phosphatidylserine vesicles as a function of the temperature at which the Ca-induced fusion takes place. PMID- 6266469 TI - Stimulation of alanine transport and metabolism by dibutyryl cyclic AMP in the hepatocytes from fed rats. Assessment of transport as a potential rate-limiting step for alanine metabolism. AB - (1) Cyclic AMP stimulated alanine transport in isolated hepatocytes by approx. 30%, in the range 0.2-5 mM alanine. (2) Alanine utilisation was also stimulated by cyclic AMP. The rates of transport and metabolism were comparable, both in the presence and absence of cyclic AMP. (3) At concentrations of alanine above 1 mM, addition of ouabain, or the reduction of the Na+ concentration, could partially inhibit transport without affecting the rate of metabolism. (4) At these alanine concentrations, stimulation of metabolism by cyclic AMP was associated with a decrease in the intracellular to extracellular alanine concentration ratio. (5) At alanine concentrations below 0.5 mM, or at higher concentrations when transport was inhibited by reducing the Na+ concentration, cyclic AMP caused an increase in the alanine concentration ratio. (6) It is concluded that at concentrations of alanine above 1 mM, alanine transport is not rate-limiting for alanine metabolism in hepatocytes from fed rats, and cyclic AMP stimulates alanine metabolism primarily by an effect on an intracellular reaction. At physiological concentrations of alanine, however, alanine transport appears to be rate-limiting in agreement with a previous report. PMID- 6266470 TI - Autoradiographic localisation of [3H]ouabain bound to cultured epithelial cell monolayers of MDCK cells. AB - [3H]Ouabain binding to intact MDCK (cultured monolayers of dog kidney) cells of 60 serial passages is dependent upon ouabain concentration, time and medium K+. By utilising high K+ incubations to estimate non-specific [3H]ouabain-binding, the concentration of ouabain giving half maximal specific binding was estimated to be 1.0 . 10(-7) M and the total maximum binding to be 2.33 . 10(5) sites/cell. Ouabain inhibition of (Na+, K+)-pump function was monitored by the cellular uptake of 86Rb over 5 min. The larger fraction of 86Rb uptake was ouabain sensitive and the ouabain concentration giving half-maximal inhibition was 2 . 10(-7) M. The cellular distribution of the (Na+ + K+)-ATPase was investigated using [3H]ouabain autoradiography of intact freeze-dried epithelial monolayers of MDCK cells grown upon millipore filter supports. Binding of [3H]ouabain is localised over the lateral cellular membranes. Autoradiographic silver grain density is close to background levels over both the apical and basal (attachment) membranes. PMID- 6266471 TI - Potential-dependent formation of single conducting ion channels in lipid bilayers induced by the polyene antibiotic levorin A. AB - The aromatic polyene antibiotic levorin A2 forms ion channels permeable to monovalent cations, in lipid membranes containing cholesterol or ergosterol. Channel conductivity is in the range 0.3-0.5 pS. The channel has two main states: conducting (open) and nonconducting (closed). The potential-dependent formation of levorin A2 channels is observed in lipid membranes. The system responsible for the ion-channel selectively is localized on the hydrophilic side of the lactone ring of the polyene molecule. PMID- 6266472 TI - Interactions of La2+ with phosphatidylserine vesicles: binding, phase transition, leakage, 31P-NMR and fusion. AB - The interaction of La2+ with phosphatidylserine vesicles is studied by differential scanning calorimetry, 140La binding, 31P-NMR chemical shifts and relaxation rates, carboxyfluorescein and [14C]sucrose release, X-ray diffraction and freeze-fracture electron microscopy. In the presence of La3+ concentrations above 1 mM and an incubation temperature of 38 degrees C, i.e., at the phase transition temperature of the complex La/phosphatidylserine, the binding ratio of La/lipid exceeds a 1/3 ratio, reaching saturation at a 1/2 ratio. Analysis, employing a modified Gouy-Chapman equation, indicates a significant increase in the intrinsic binding constant of La/phosphatidylserine when the La3+ concentrations exceeds the threshold concentration for leakage. The analysis illustrates that at the molecular level the binding of La3+ can be comparable to or even weaker than that of Ca2+, but that even when present at smaller concentrations La3+ competes with and partially displaces Ca2+ from membranes or other negatively charged surfaces. The results suggest that the sequence La3+ greater than Ca2+ greater than Mg2+ reflects both the binding strength of these cations to phosphatidylserine as well as their ability to induce leakage, enhancement of 31P spin-lattice relaxation rates, fusion and other structural changes. The leakage, fusion, and other structural changes are more pronounced at the phase transition temperature of the La/lipid complex. PMID- 6266473 TI - Reversible electrical breakdown of squid giant axon membrane. AB - Charge pulse relaxation experiments were performed on squid giant axon. In the low voltage range, the initial voltage across squid axon membrane was a linear function of the injected charge. For voltages of the order of 1 V this relationship between injected charge and voltage across the membrane changes abruptly. Because of a high conductance state caused by these large electric fields the voltage across the membrane cannot be made large enough to exceed a critical value, Vc, defined as the breakdown voltage, Vc has for squid axon membrane a value of 1.1 V at 12 degrees C. During breakdown the specific membrane conductance exceeds 1 S. cm-2. Electrical breakdown produced by charge pulses of few microseconds duration have no influence on the excitability of the squid axon membrane. The resealing process of the membrane is so fast that a depolarizing breakdown is followed by the falling phase of a normal action potential. Thus, membrane voltages close to Vc open the sodium channels in few microseconds, but do not produce a decrease of the time constant of potassium activation large enough to cause the opening of a significant percentage of channels in a time of about 10 mus. It is probable that the reversible electrical breakdown is mainly caused by mechanical instability produced by electrostriction of the membrane (electrochemical model), but the decrease in the Born energy for ion injection into the membrane, accompanying the decrease in membrane thickness, may play also an important role. Because of the high conductance of the membrane during breakdown it seems very likely that this results in pore formation. PMID- 6266474 TI - Mode of action of colicin ib: formation of ion-permeable membrane channels. AB - Addition of purified colicin Ib to whole Escherichia coli cells or cytoplasmic membrane vesicles inhibits their subsequent ability to generate a membrane potential. In addition, this colicin is shown to bring about a voltage-dependent increase in the conductance of an artificial planar bilayer membrane prepared from soybean phospholipids. This results from the formation of ion-permeable channels. These data provide strong evidence that the depolarization of Escherichia coli cells by this colicin results from an Ib-induced increase in membrane permeability to ions. PMID- 6266475 TI - (Na+ + K+)-ATPase : phosphorylation-dependent cross-linking of the alpha-subunits in the presence of Ca2+ and o-phenanthroline. AB - In previous studies we had demonstrated that in the presence of 0.25 mM Cu2+ and 1.25 mM o-phenanthroline, cross-linking of the alpha-subunits of Na+ + K+) dependent adenosine triphosphatase was induced by the addition of Na+ + ATP, and that the formation of the alpha,alpha-dimer was preceded by that of phosphoenzyme. The purpose of the present studies was the further evaluation of the role of phosphoenzyme in the process of cross-linking. Na+ + UTP did not induce cross-linking unless Mg2+ was also added. In contrast, Na+ + ATP-induced cross-linking did not require the addition of Mg2+. The different effects of ATP and UTP in the absence of added Mg2+ could be accounted for by the presence in the enzyme preparation of bound Mg2+ which supported enzyme phosphorylation by ATP but not by UTP. When the enzyme was phosphorylated by Pi, in the presence of Mg2 and ouabain, and the exposed to Cu2+ and o-phenanthroline, the alpha,alpha dimer was obtained. Under these conditions, Na+ blocked both phosphorylation and cross-linking. These results indicate that it is the formation of phosphoenzyme per se that leads to conformational transitions favorable to cross-linking. They also suggest that Cu2+ and o-phenanthroline participate in the cross-linking reaction, but not in the phosphorylation reactions. In the digitonin-treated enzyme, Na+ and ATP induced the formation of phosphoenzyme, but not that of alpha,alpha-dimer. These findings indicate that in addition to phosphorylation, a proper orientation o alpha-subunits in an oligomer is also necessary for cross linking. PMID- 6266476 TI - Exfoliation of membrane ecto-enzymes in the form of micro-vesicles. AB - Cultures from various normal and neoplastic cell lines exfoliated vesicles with 5'-nucleotidase activity which reflected the ecto-enzyme activity of the parent monolayer culture. The ratio of 5'-nucleotidase to ATPase activity in the microvesicles indicated that cellular ecto-ATPase was conserved in the exfoliative process. Phospholipids of the microvesicles contained significantly increased amounts of sphingomyelin and total polyunsaturated fatty acids. It was concluded that the shedded vesicles constituted a select portion of the plasma membrane. Examination by electron microscopy showed the vesicles had an average diameter of 500 to 1000 nm and often contained a second population of vesicles about 40 nm in diameter. As much as 70% of the plasma membrane ecto-5' nucleotidase activity of a culture was released into the medium over a 24-h period. Phosphoesterhydrolases from C-6 glioma or N-18 neuroblastoma microvesicles dephosphorylated cell surface constituents when in contact with monolayer cultures. Exfoliated membrane vesicles may serve a physiologic function; it is proposed that they be referred to as exosomes. PMID- 6266477 TI - The rate of osmotic hemolysis: a relationship with membrane bilayer fluidity. AB - A first-order semilogarithmic plot of the decrease in turbidity that takes place during hemolysis is used to define an apparent rate of hemolysis. The effect on this rate of hemolysis of various membrane modifications is studied. Triton X 100, ethanol and chlorpromazine, which dissolve into the membrane, all increase the rate of hemolysis, even though the same concentration of ethanol and chlorpromazine has been shown to decrease the osmotic fragility. Glutaraldehyde, azodicarboxylic acid-bisdimethylamide (diamide) and intracellular Ca2+ are used to produce cross-links on membrane proteins. All of these reagents decrease cell deformability but have different effects on the rate of hemolysis, with Ca2+ increasing, glutaraldehyde decreasing and diamide producing almost no effect on the rate. These modifications are also found to alter the ESR spectra of the stearic acid spin-label, 2-(14-carboxytetradecyl)-2-ethyl-4,4-dimethyl-3 oxazolidinyloxyl, which probes mobility in the hydrophobic core of the lipid bilayer. A correlation between the effect of membrane modifications on bilayer fluidity and the rate of hemolysis suggests that the rate-limiting process which determines the rate of hemolysis involves rupturing of the bilayer. PMID- 6266478 TI - Phospholipid chain immobilization and steroid rotational immobilization in acetylcholine receptor-rich membranes from Torpedo marmorata. AB - 1. The ESR spectra of both phosphatidylcholine and phosphatidylethanolamine spin labels reveal an immobilized lipid component (tau R greater than or equal to 50 ns), in addition to a fluid component (tau R approximately 1 ns), in acetylcholine receptor-rich membranes prepared from Torpedo marmorata electroplax according to the method of Cohen et al. (Cohen, J.B., Weber, M., Huchet, M. and Changeux, J.-P. (1972) FEBS Lett. 26, 43--27). 2. The ESR spectra of the androstanol spin label display a component corresponding to molecules which are immobilized with respect to rotation about the long molecular axis (tau R greater than or equal to 50 ns), in addition to the fluid lipid bilayer component in which the molecules are rotating rapidly about their long axes (tau R approximately 1 ns). This immobilized component is observed throughout the temperature range 2--22 degrees C, at an approximately constant relative intensity of approx. 45% of the total, which is quantitatively the same as previously observed with fatty acid spin labels. PMID- 6266479 TI - The effect of salt on the binding of the eucaryotic DNA nicking-closing enzyme to DNA and chromatin. AB - The optimum monovalent cation concentration (Na+ or K+) for the relaxation of superhelical DNA by the rat liver nicking-closing enzyme under conditions of DNA excess was found to be 150-200 mM. The detection of a nicked DNA species after stopping a reaction with alkali depends on having a high molar ratio of enzyme to DNA and is maximal between 50 and 100 mM monovalent cation. Varying the salt concentration from 15 to 200 mM appears to have no effect on the catalysis of the nicking -closing reaction by the enzyme. Instead different salt optima in these two assays can be explained by the observation that the nicking-closing enzyme acts by a processive mechanism below 100 mM salt and becomes nonprocessive above 150 mM. The salt elution of the nicking-closing enzyme from resting cell chromatin appears to be similar to that which one would expect for the elution of the enzyme from naked DNA. However, greater than 70% of the chromatin associated enzyme activity remained bound to chromatin from growing cells at 300 mM salt, a concentration at which there is no significant binding to naked DNA in vitro. PMID- 6266480 TI - Overproduction of the EcoRII endonuclease and methylase by Escherichia coli strains carrying recombinant plasmids constructed in vitro. AB - Recombinant DNA molecules were constructed from the plasmid pIL203 and the EcoRI fragment of N3 plasmid containing EcoRII endonuclease and methylase genes and also a gene for resistance to sulfanilamide. The pIL203 plasmid, used as a vector, consisted of the Bam HI-EcoRI-fragment of the plasmid pBR322 conferring resistance to ampicillin and the Bam HI-EcoRI-fragment of lambda phage containing promoters, a thermosensitive mutation in the cI gene and a suppressible amber mutation in the cro gene. Ampicillin-sulfanilamide-resistant clones were selected and tested for their restriction and modification phenotype. The recombinant plasmid DNA, isolated from ApRSuR-resistant clones, which restricted and modified phage lambda imm21 with EcoRII specificity, had the EcoRI-fragment with EcoRII genes in a single orientation. The recombinant plasmid pSK323 was transferred into E. coli strains with su-, su1, su2 or su3 phenotypes. The synthesis of products of EcoRII genes by these strains grown at 37 degrees C is increased by 10--50-fold. PMID- 6266481 TI - DNAase I digestion of early, middle, and late S phase replicating DNA in murine leukemia L5178Y cells. AB - Cellular DNA from a synchronized population of cultured mouse L5178Y cells was labeled with [3H]thymidine at three times during the S stage: early, middle and late S phases. The deoxyribonuclease I digestability of DNA from these three periods in the subsequent cell cycle indicated that the early S phase replicating DNA had higher enzymatic susceptibility at G1 and early S phases than at middle and late S phases, while the middle and late S phase replicating DNA demonstrated a low susceptibility throughout the cell cycle. This suggests that most, if not all, of transcriptionally active DNA is replicated very early in the S phase. PMID- 6266482 TI - Fluorescent-light-induced lethality and DNA repair in normal and xeroderma pigmentosum fibroblasts. AB - Cell survival and induction of endonuclease-sensitive sites in DNA were measured in human fibroblast cells exposed to fluorescent light or germicidal ultraviolet light. Cells from a xeroderma pigmentosum patient were hypersensitive to cell killing by fluorescent light, although less so than for germicidal ultraviolet light. Xeroderma pigmentosum cells were deficient in the removal of fluorescent light-induced endonuclease sites that are probably pyrimidine dimers, and both the xeroderma pigmentosum and normal cells removed these sites with kinetics indistinguishable from those for ultraviolet light-induced sites. A comparison of fluorescent with ultraviolet light data demonstrates that there are markedly fewer pyrimidine dimers per lethal event for fluorescent than for ultraviolet light, suggesting a major role for non-dimer damage in fluorescent light lethality. PMID- 6266483 TI - Hybrid plasmids carrying part of the Rous sarcoma virus-specific leader sequence. AB - 'Strong-stop' DNA, complementary to the 5'-terminal 101 nucleotides of Rous sarcoma virus genomic RNA and subgenomic mRNAs can be used to isolate RSV specific mRNA from infected cells. To analyse leader sequences of these mRNAs and to study the mechanism of their translation, relatively large quantities of strong-stop DNA are required. The construction of four plasmids carrying useful strong-stop DNA sequences for mRNA isolation is described. One such hybrid plasmid carries a DNA insertion containing sequences derived from a region starting 42 nucleotides from the 5'-end of RSV RNA, and ending at the tRNATry primer attachment site. Since this plasmid lacks the 20-nucleotide terminal repeat sequence it can be used for the specific isolation of 5'-end fragments of RSV-specific mRNAs and of complementary DNA transcripts of these fragments. PMID- 6266484 TI - DNA repair enzyme deficiency and in vitro complementation of the enzyme activity in cell-free extracts from ataxia telangiectasia fibroblasts. AB - Three ataxia telangiectasia homozygotes, one heterozygote and normal fibroblast strains were compared as to the capacity of their cellular extracts to enhance the priming activity of gamma-irradiated colicin E1 DNA for purified DNA polymerase (EC 2.7.7.7) of Escherichia coli. It was found that homozygotes had substantially lower activity than normal strains, while no difference was detected between the heterozygote and normal strains. In vitro complementation of the activity occurred between extracts of certain strains of homozygotes, allocating them to two complementation groups. PMID- 6266485 TI - Characteristics of chromatin preparations from herpes simplex virus infected cells. AB - Chromatin isolated from herpes simplex virus type 1-infected baby hamster kidney cells contains a number of tightly associated virus-induced polypeptides. A subset of these proteins bind to immobilized DNA in vitro (Vmw 175, 155, 130, 63, 43, 38/39). Virus-induced polypeptides extractable with acid from infected cell chromatin include Vmw 155, the major capsid protein of herpes simplex virus type 1 virions, and Vmw 63 and 38/39 which are heterogeneous with respect to charge and are phosphorylated. These chromatin preparations, in the presence of deoxynucleoside triphosphates and MgCl2 were capable of synthesizing viral and cell DNA in a reaction which was stimulated by the addition of ATP, riboNTPs and potassium acetate. In vitro synthesized viral DNA co-sedimented with prelabelled parental DNA but the single-stranded product was smaller than parental DNA. Density labelling indicated that extensive synthesis was taking place and all BamHI fragments of viral DNA were represented by the DNA synthesized in vitro. PMID- 6266486 TI - Conformational changes of yeast tRNAPhe upon interaction with intercalators probed by nuclease digestion. AB - The conformational changes of yeast-tRNAPhe induced by various intercalators have been studied using limited digestions with nucleases S1 and T1. The results show an increased sensitivity to T1 in the D-loop, suggesting a weakening of the D loop-T-loop interaction. Furthermore, the results are best explained by a non intercalative binding of the eyes, probably in the D-loop-T-loop cavity. PMID- 6266487 TI - Chemical characterization of the homogeneous collagenase from Clostridium histolyticum. AB - Pure collagenase (clostridiopeptidase A, EC 3.4.24.3) having a molecular weight of 70 000 was obtained from the culture medium of Clostridium histolyticym by a combination of ultrafiltrations, molecular sieve, affinity and hydrophobic chromatography. The value of its specific activity is the highest of those described previously but 6-times lower than that of the collagenase from Achromobacter iophagus (EC 3.4.24.8). Its amino acid composition differs from previous data, namely by the presence of cysteine, methionine, tryptophan and O phosphoserine residues. In contrast to Achromobacter collagenase it does not dissociate in subunits during the deactivation by EDTA or LiCl/glycine buffer at pH 10.5. Existence of multiple forms of Clostridium collagenase previously described is discussed as being due to autolysis of a single molecular species or to a different degree of phosphorylation. PMID- 6266488 TI - Enzymatic properties of an acid carboxypeptidase from Aspergillus niger var. macrosporus. AB - Acid carboxypeptidase (peptidyl-L-amino-acid hydrolase, EC 3.4.16.1) isolated from Aspergillus niger var. macrosporus was investigated in regard to its kinetic parameters for two synthetic substrates. The optimum pH of peptidase activity toward Z-Glu-Tyr-OH was pH 3.0 Km and kappa cat values were 4.0 . 10(-3) M and 270 s-1 at pH 3.0 and 30 degrees C. The optimal pH of esterase activity toward Bz Arg-OEt was pH 5.2 Km and kappa cat for esterolytic activity were 6.1 . 10(-4) M and 1500 s-1 at pH 5.0 and 30 degrees C. The enzyme released expected amino acids sequentially from the carboxyl ends of S-beta-aminoethylated ribonuclease A and the B-chain of oxidized insulin, demonstrating carboxypeptidase activity of the enzyme. The enzyme was inactivated by diisopropylphosphorofluoridate and phenyl methanesulfonyl fluoride. In the reaction with [14C]diisopropylphosphorofluoridate, the amount of [14C]diisopropylphosphoryl group incorporated into the enzyme in complete inactivation was estimated as 2 mol/mol enzyme. PMID- 6266489 TI - A novel phosphodiesterase I from the soluble fraction of erythrocytes. AB - A previously unrecognized erythrocyte phosphodiesterase I with activity against thymidine-5'-monophospho-p-nitrophenyl ester is described. The enzyme is present in the soluble fraction of the erythrocyte, and was purified about 500-fold by chromatography using DEAE-cellulose, followed by gel chromatography with Sephadex G-200. Erythrocyte phosphodiesterase I has a molecular weight of about 70 000, when fully active as a monomer. Its pI is 5.4 and the pH optimum is 8.5. The Km value for thymidine-5'-monophospho-p-nitrophenyl ester is rather high, about 4 mmol/l. The enzyme has a barely detectable nucleotide pyrophosphatase activity. It is extremely sensitive to SH-inhibitors such as N-ethyl-maleimide, p chloromercuribenzoate and disulphides (a reversible 50% inhibition was obtained by cystamine, 0.01 mmol/l). It is a metalloenzyme with loosely bound metal, and is stimulated by Mg2+. This activation by Mg2+ is counteracted by Zn2+. Gel chromatography revealed that the enzyme is a monomer in the presence of Mg2+. When inhibited by Zn2+, it forms polymers that can be reconverted to the monomer by thiols. All of the above properties of the erythrocyte enzyme support the conclusion that it is different from plasma membrane phosphodiesterase I (oligonucleate 5'-nucleotidohydrolase, EC 3.1.4.1). PMID- 6266490 TI - Isolation and properties of glyceraldehyde-3-phosphate dehydrogenase from a sturgeon from the Caspian Sea and its interaction with spin-labeled NAD+ derivatives. AB - Glyceraldehyde-3-phosphate dehydrogenase (D-glyceraldehyde-3-phosphate: NAD+ oxidoreductase (phosphorylating), EC 1.2.1.12) was isolated from a sturgeon, Huso huso, from the Caspian Sea. It is closely related to the enzyme from a Pacific sturgeon, Acipenser transmontanus, with respect to amino acid composition, steady state kinetics and coenzyme binding. The latter, as studied by means of a spin labeled derivative of NAD+, is negatively cooperative exhibiting a Hill coefficient of 0.84 at 12 degrees C. Two derivatives of NAD+ spin-labeled at N6 or C8 of the adenine ring were found to be active coenzymes with maximum velocities reaching 35 or 45% of the value for NAD+ itself. When more than two equivalents of either spin-labeled NAD+ are bound to the enzyme spin-spin interactions are observed in the ESR spectra. Distances between the nitroxide radicals (8--9 A) calculated from the observed splittings are in excellent agreement with data predicted from the crystal structure of the lobster enzyme when the coenzyme is bound in an anti-conformation of the adenine moiety about the glycosidic bond to all four subunits. PMID- 6266491 TI - Separation and properties of molecular forms of alpha-galactosidase and alpha-N acetylgalactosaminidase from blood lymphocytes and lymphoid cell lines transformed by Epstein-Barr virus. PMID- 6266492 TI - Collagen biosynthesis by human skin fibroblasts. III. The effects of ascorbic acid on procollagen production and prolyl hydroxylase activity. AB - Human skin fibroblasts were cultured under conditions optimized for collagen synthesis, and the effects of ascorbic acid on procollagen production, proline hydroxylation and the activity of prolyl hydroxylase were examined in cultures. the results indicated that addition of ascorbic acid to confluent monolayer cultures of adult human skin fibroblasts markedly increased the amount of [3H]hydroxyproline synthesized. Ascorbic acid, however, did not increase the synthesis of 3H-labeled collagenous polypeptides assayed independently of hydroxylation of proline residues, nor did it affect the amount of prolyl hydroxylase detectable by an in vitro enzyme assay. Also long-term cultures of the cells or initiation of fibroblast cultures in the presence of ascorbic acid did not lead to an apparent selection of a cell population which might be abnormally responsive to ascorbic acid. Thus, ascorbic acid appears to have one primary action on the synthesis of procollagen by cultured human skin fibroblasts: it is necessary for synthesis of hydroxyproline, and consequently for proper triple helix formation and secretion of procollagen. PMID- 6266493 TI - Short-term stimulation of net glycogen production by insulin in rat hepatocytes. AB - Isolated liver cells from 24 h starved rats were incubated in Krebs-Ringer buffer containing 4% albumin. In the presence of 10, 20 and 30 mM glucose, addition of insulin stimulated net glycogen production by 52, 39 and 20%, respectively. 2 . 10(-9) M insulin was required for half-maximal stimulation. Increases of glycogen production and of glycogen synthase a activity were observed after 15-30 min of incubation with insulin. The stimulatory effect of insulin was additive to that of lithium. In agreement with the literature, insulin antagonized the inhibitory action of suboptimal doses of glucagon on glycogen deposition whereby a decrease of glucagon-elevated cyclic AMP levels was observed. In addition, we found that insulin also decreased the basal cyclic AMP levels in the absence of added glucagon by 22%. It is concluded that physiological concentrations of insulin stimulate net glycogen deposition in hepatocytes from fasted rats; the decrease of basal cyclic AMP levels upon insulin addition may play a role in the mechanism of the hormone action. PMID- 6266494 TI - Cyclic nucleotide-dependent phosphorylation of endogenous proteins in bovine adrenocortical cell membranes. AB - Activation of one or more cyclic AMP-dependent protein kinases has been suggested as an intermediate step in ACTH-stimulated adrenal cell steroidogenesis. Phosphorylation of a number of proteins from different subcellular fractions has been reported but those phosphorylation events which are relevant to the steroidogenic process have not yet been identified. In this paper we report that plasma membrane enriched fractions from bovine adrenal cortex retain the ability to phosphorylate endogenous membrane proteins and that phosphorylation of these acceptors is markedly enhanced by cyclic AMP or, to a lesser extent, by cyclic GMP. Cyclic nucleotide-dependent phosphorylation was most marked in protein acceptors of 191 000, 148 000, 138 000, 107 000, 65 000, 60 000 and 27 000 daltons. Cyclic nucleotide stimulation of phosphorylation was rapid (within 10 s), and is consistent with the rapid onset of ACTH-stimulated steroidogenesis. PMID- 6266495 TI - Distinct effects of the C-terminal octapeptide of cholecystokinin and of a cholera toxin pretreatment of the kinetics of rat pancreatic adenylate cyclase activity. AB - (1) The kinetic parameters of rat pancreatic adenylate cyclase were evaluated, using GTP, p[NH]ppG or GTP gamma S as nucleotide activator, cholecystokinin as peptide hormone, and GDP beta S and dibutyryl cyclic GMP as inhibitors of guanosine triphosphate and CCK-8, respectively. The time courses of activation and the degree of activation at steady state (EA/ETOT) were compatible with a simple two-state model of activation-deactivation based on a pseudo-monomolecular activation process (rate constant kappa+1), and a deactivation process (rate constant kappa off) that included, depending on the activating nucleotide, the hydrolysis of GTP (rate constant kappa 2) and/or the dissociation of the intact nucleotide (rate constant kappa-1), so that EA/ETOT = kappa+1/(kappa+1 + kappa 2 + kappa-1). (2) The hormone CCK-8 increased the value of kappa+1 with GTP dose dependently, from 0.2 to 10.9 min-1. The value of kappa-1 increased 0.01 to 0.3 min-1 but the value of kappa 2 was unaltered at 7 min-1, so that EA/ETOT increased 15-fold, from 4% to 61%. (3) A cholera toxin pretreatment at 30 micrograms/ml allowed also a large increase in EA/ETOT with GTP (up to 51%) but the underlying mechanism was different. It consisted of a 14-fold decrease in the kappa off value of the GTP-activated enzyme (from 7 min-1 to 0.5 min-1) that corresponded to a reduction in GTPase activity. When testing the system with p[NH]ppG, two added effects of the cholera toxin pretreatment were observed: a 4 fold increase in the value of kappa+1 (from 0.2 to 0.8 min-1) and the occurrence of a significant 0.3 min-1 value for kappa-1. PMID- 6266496 TI - Subcellular distributions of UDP-galactose:polysaccharide transferase and UDP glucose pyrophosphorylase involved in biosynthesis of prespore-specific acid mucopolysaccharide in Dictyostelium discoideum. AB - During the development of a cell aggregate of Dictyostelium discoideum into a fruiting body, an antigenic acid mucopolysaccharide is synthesized only in the prespore cells of a cell mass. In this study, the subcellular distributions of UDPgalactose:polysaccharide transferase and UDPglucose pyrophosphorylase involved in biosynthesis of the mucopolysaccharide were determined. The transferase was specifically localized in the smaller vesicles with lighter density than the prespore-specific vacuoles identifiable electronmicroscopically. In contrast to the enzyme, the antigenic mucopolysaccharide was exclusively localized in the prespore-specific vacuoles. Unlike the transferase, UDPglucose pyrophosphorylase was confined to the soluble fraction. The sucrose gradient profiles of the transferase activity in the 5000 X g supernatant gave two main peaks. When the profiles wee compared among standing and migrating slugs and culminating cell mass, the difference in the profiles closely reflected the state of biosynthesis of the acid mucopolysaccharide in each developmental stage. PMID- 6266497 TI - Glycogen synthase activity in Chinese hamster ovary cells. Studies with wild-type and mutant cells defective in cyclic AMP-dependent protein kinase. AB - Glycogen synthase (EC 2.4.1.11) activity was studied in cell extracts from wild type Chinese hamster ovary (CHO) cells and three mutants resistant to cyclic AMP effects on cell shape and cell growth. Based on the capacity of crude extracts to phosphorylate exogenous histone, two of the mutants appeared to have altered cyclic AMP-dependent protein kinase (EC 2.7.1.37) and one of them had apparently normal amounts of kinase activity. Glycogen synthase activity was present in comparable amounts in wild-type and all three mutant strains in a presumably inactive phosphorylated form since activity was virtually completely dependent upon the presence of glucose 6-phosphate. The enzyme could be partially dephosphorylated by endogenous phosphatases and rephosphorylated by exogenous cyclic AMP-dependent protein kinase. Attempts to find culture conditions (e.g. glucose starvation) or cell treatment (e.g. insulin) which might activate glycogen synthase in intact cells were unsuccessful. since glycogen synthase activity present in CHO cells was independent of the level of cyclic AMP dependent kinase, we conclude that cyclic AMP-dependent protein kinase does not play a critical role in regulating the state of phosphorylation of the synthase. PMID- 6266498 TI - Distribution of adenosine metabolising enzymes between adipocyte and stromal vascular cells of adipose tissue. AB - Rat adipose tissue was digested with collagenase and separated into adipocytes and stromal-vascular cells. The adipocytes accounted for 40% of the total adipose tissue adenosine deaminase activity, 32% of 5'-nucleotidase activity and 87% of adenosine kinase activity. This distribution suggests that adipocyte are the major cell type involved in adenosine utilization in adipose tissue. Furthermore, it suggests that the high sensitivity of isolated adipocytes to adenosine is representative of their sensitivity of isolated adipocytes to adenosine is representative of their sensitivity in vivo. PMID- 6266499 TI - Maximum activities of enzymes involved in adenosine metabolism in adipose tissue of rats and mice under conditions of variations in insulin sensitivity. PMID- 6266500 TI - Epstein-Barr virus co-reconstituted with Sendai virus envelopes infects Epstein Barr virus-receptor negative cells. AB - Epstein-Barr virus (EBV) was co-reconstituted with Sendai virus envelopes. The reconstituted "hybrid' virus could bind and penetrate into EBV-receptor negative cells. Using this approach, T-cell-derived human and mouse leukemia cells, human T-lymphocytes and mouse spleen cells were successfully infected as judged by the induction of EBV-determined antigens and stimulation of DNA synthesis. The T-cell derived human leukemia line Molt-4, that can absorb EBV but without virus penetration, could be also infected by the reconstituted EBV. PMID- 6266501 TI - The hamster adipocyte adenylate cyclase system. II. Regulation of enzyme stimulation and inhibition by monovalent cations. PMID- 6266503 TI - Regulation of cardiac cyclic GMP-dependent protein kinase. PMID- 6266502 TI - Subcellular distribution of enzymes in the yeast saccharomycopsis lipolytica, grown on n-hexadecane, with special reference to the omega-hydroxylase. AB - The subcellular localization of the omega-hydroxylase of Saccharomycopsis lipolytica was assessed by the analytical fractionation technique, originally described by de Duve C., Pressman, B.C., Gianetto, R., Wattiaux, R. and Appelmans, F., and hitherto little, if at all, applied to yeasts. Protoplasts were separated in six fractions by differential centrifugation. Some of these fractions were further fractionated by density gradient centrifugation. The distribution of omega-hydroxylase and 15 other constituents chosen as possible markers of its subcellular entities. (1) Mitochondria were characterized by particulate malate dehydrogenase, particulate Antimycin A-insensitive NADH cytochrome c reductase, oligomycin-sensitive and K+-stimulated ATPase pH 9. (2) Most if not all of the catalase and urate oxidase is peroxisomal. (3) Free ribosomes account for most RNA. (4) Nucleoside diphosphatase is for the first time reported in a yeast and appears to belong to an homogeneous population of small membranes. (5) The soluble compartment contains magnesium pyrophosphatase, alkaline, 5'-nucleotidase and part of the NADH-cytochrome c reductase. Latent arylesterase and ATPase pH 7 have an unspecific distribution. Alkaline phosphodiesterase I has not been detected. PMID- 6266505 TI - [Analysis of the excitable properties of an artificial membrane containing amphotericin B in the presence of cationic blockers]. AB - A mathematical model was developed to describe the excitability of the amphotericin B--containing membrane with ionic blockers. The model is equivalent to the Hodgkin--Huxley model of the Na--channel with only one activating particle. A variety of the blockers parameters were evaluated with which the artificial membrane acquires excitable properties (generation of action potential, a self--oscillatory mode of pulse generation, trigger--like changes in the resting potential). The possibilities of constructing artificial excitable membranes with a cooperative activation of conductivity are discussed. PMID- 6266504 TI - [Participation of iron in OH-radical formation in a system generating a superoxide anion-radical]. PMID- 6266506 TI - [Properties of conductivity channels induced in phospholipid bilayer membranes by alpha-staphylotoxin]. AB - Interaction between alpha-straphylotoxin (alpha-T) and synthetic phospholipid membranes was shown to be accompanied by the formation of conductivity channels of different amplitude. Dependence of channel conductivity on salt concentration, medium pH, as well as selectivity for different cations and anions was determined. Current--voltage characteristics of BPhM modified by alpha-T were measured. The conductivity fluctuations observed are suggested to be concerned with the initiation of phospholipid domens (with changed mobility of their fatty acid chains) in the bilayer structure. PMID- 6266507 TI - [EPR study of the respiratory chain of Endomyces magnusii yeasts during cell growth on glycerin]. PMID- 6266508 TI - [Study of spin-labeled microsomal membrane proteins by their reaction with ascorbic acid]. AB - Kinetics of the reduction of nitroxyl radicals bound to SH-groups of microsome membrane proteins by ascorbic acid was investigated. The reduction involves two steps. During the first quick step mainly the radicals with weak immobilization located on the membrane surface are reduced. At the second slow step more immobilized radicals located in hydrophobic membrane regions take part in the reaction. A kinetic analysis of the process showed that the slow step is not determined by the slow movement of protein or its fragments, for instance, from the membrane depth to its surface, and apparently is conditioned by lower ascorbic acid concentration in the membranes. PMID- 6266509 TI - [EPR study of high potential iron-sulfur centres in mitochondria of yeasts Endomyces magnusii and of rat liver]. AB - The curves of temperature relationship of signal intensity (amplitude) with g = 2.02-2.03 may serve as a test for identification of iron-sulfur centres of S-3 and aconitase at different metabolic states of mitochondria in the course of their reduction with various substrates PMID- 6266512 TI - [Proton permeability and electric breakdown of phospholipid membranes after UV irradiation]. AB - Lipid peroxidation induced in bilayer lipid membranes (BLM) by UV-irradiation leads to two types of effects: selective in proton permeability and electric breakdown of the membranes. Both phenomena are always observed but the contribution of each in the membrane conductivity increase depends on the lipid nature (degree of unsaturation of fatty acids) and the value of transmembrane applied to BLM or generated by the membrane itself. PMID- 6266510 TI - [Protein from beef heart mitochondria inducing the potassium channel conductivity of bilayer lipid membrane]. AB - Protein (M. m. 60 000) inducing selective potassium conductance of bilayer lipid membranes (BLM) was isolated from mitochondria and homogenate of the beef heart. This protein was obtained by means of alcohol (ethanol) extraction and was purified by gel-filtration on Sephadex G-15 and G-50 followed by electrophoresis in the 10% polyacrylamide gel. 6-10 g/ml of the protein produced the conductivity channels on BLM with amplitude divisible of 24 +/- 4 pmho. The channels of 175 +/ 7 pmho were the most typical ones. The modification of BLM by K+-transport in protein under the conditions of potassium gradient resulted in the appearance of the membrane potential close to the theoretical Nernst potential. PMID- 6266514 TI - [Initiation of anion-selective ionic channels in bilayer membranes at lipid phase transitions]. AB - A study was carried out to electric parameters of single ionic channels initiated at phase transition of bromidmetilate 1,2-distearoyl-rac-glycero-3-(O-beta dimethylaminoethyl)-methylphosphonate, whose molecules under conditions given below are possibly charged. It has been shown that changes of transmembrane current appear at phase transition temperature. Comparison between ionic selectivity of channels initiated at Tph.t in the membranes of DSL and its phosphate analog suggests that the channel walls initiated at phospholipid phase transitions are covered with polar groups of molecules. PMID- 6266513 TI - [Evaluation of the effect of water on the kinetics of transmembrane transport of ions along narrow ionic channels]. AB - An equation for the velocity of ion transport along channels with a unidirectional flux of water molecules and ions was derived. It has been shown that the ionic flux linked between water transport is negligible as compared with the overall ionic flux. The effect of water is to diminish the maximum transport velocity only. PMID- 6266511 TI - [Effect of falloidin on permeability of intercellular channels for inorganic ions and fluorescein]. AB - It has been shown on larva gland that falloidin - a toxic of toadstool inducing an increased number of membrane microfilaments-affects the efficiency of intercellular transfer of small inorganic ions and molecules of organic dye fluorescein-Na. The data obtained are in favour of the participation of microfilaments in the regulation of intercellular diffusion communication. PMID- 6266515 TI - [Binding of a tritiated enkephalinergic analog (FK 33-824) to a mitochondrial fraction of rat brain]. AB - FK-33-824 (Try-D-Ala-Gly-MePhe-Met(O)ol) is a potent enkephalin analog which has been tritium labelled with a high specific radioactivity (41 Ci/mmole). The labelled drug exhibits specific and saturable binding to rat brain crude mitochondrial fraction. Specific binding is inhibited by low concentrations of morphine, levallorphan and beta-endorphin, suggesting that FK 33-824 [3H] binds preferentially to mu opiate sites. Binding studies at equilibrium and kinetics of formation and dissociation of the labelled ligand-receptor complex indicate that FK 33-824 [3H] binds to two classes of specific sites. Their affinities are distinguishable at 0 degree (KD = 1.3 and 5.8 nM) and very close to each other at 37 degree (KD = 1.9 nM). PMID- 6266516 TI - Characterization of an histone kinase activity specifically found in hyperfunctioning benign thyroid tumors. PMID- 6266517 TI - [Interaction of D-Ala2-[Tyr-3,5-3H]enkephalin(5-D-Leu) with opiate receptors of rat brain]. AB - Some kinetic features of D-Ala2-[Tyr-3.5-3H]enkephalin (5-D-Leu) binding to opiate receptors of rat brain were studied. It was shown that the Leu-enkephalin D analog interacts with the high and low affinity binding sites of opiate receptors, the equilibrium constants being equal to 0.71 and 8.4 nM, respectively. The rate constant for the label association with the high affinity binding sites in 2 . 10(8) M-1 min-1; those for the label dissociation from the opiate receptor binding sites with high and low affinities are 7.2 . 10(-3) and 0.16 min-1, respectively. Hence, the half-life time of these complexes is 95.7 and 4.3 min, respectively. Na+, K+ and Li+ markedly decrease the specific finding of the label, while Mg2+, Mn2+ and Ca2+ at the concentrations studied markedly increase its specific binding. It is concluded that the Leu-enkephalin D-analog under study acts as a morphine agonist and reveals a much higher affinity for rat brain opiate receptors than does Leu- or Met-enkephalin. This makes it a useful tool for study of the enkephalin reception under normal and pathological conditions. PMID- 6266518 TI - [Interaction of SV40 T-antigen with homologous and heterologous DNA]. AB - Using the DNA filter binding assay, the effects of ionic strength and pH on SV40 T-antigen interaction with viral DNA were studied. The apparent association constants for T-antigen binding to SV40 DNA in Scatchard coordinates in the presence of 40 mM NaCl are equal to 0.67 . 10(6) M-1 (pH 6.0) and 0.86 x 10(7) M 1 (pH 7.4). These data indicate that the interaction between T-antigen and SV40 DNA is more specific at pH 7.4. The coincident values of association constants for T-antigen binding to viral and cellular DNAs (Ka = 0.9 x 10(7) M-1 for cellular DNA) at pH 7.4 and the absence of competition between the two DNA species upon binding with T-antigen suggest that viral and cellular DNAs possess similar sites for T-antigen binding. Denatured DNA competes with viral DNA only at pH 6.0, when the T-antigen--SV40 DNA interaction is less specific. PMID- 6266519 TI - [Effect of pH on Ca-binding properties of calmodulin and on its interaction with Ca-dependent phosphodiesterase of cyclic nucleotides]. AB - The fluorescence of dansyl immobilized on bovine brain calmodulin is sensitive to Ca2+. This effect is due to Ca2+ attachment to specific Ca2+-binding sites of calmodulin and is maintained within a wide range of pH. The native and dansyl modified calmodulin preparations exert similar activating effects on Ca-dependent phosphodiesterase of cyclic nucleotides and have practically the same affinity for the enzyme. Using fluorescence measurements of the calmodulin--dansyl conjugate, it was shown that the decrease of pH from 9.0 down to 6.0 gradually decreases the constant of Ca2+ binding to calmodulin from 1.5 . 10(10) M-1 to 1.6 . 10(6) M-1. This decrease of pH does not affect the calmodulin affinity for phosphodiesterase. The activating effect of calmodulin on phosphodiesterase is more pronounced at acidic pH values (6.0-7.0) than at alkaline pH values (8.0 9.0). PMID- 6266520 TI - [Characterization of the kinase activity of bovine adrenal pyruvate dehydrogenase complex]. AB - In the presence of [gamma-32P]ATP the bovine adrenal pyruvate dehydrogenase complex accepts the label simultaneously and becomes inactivated. This suggests the existence of kinase in the composition of the complex as is typical of the complexes from other animal sources. The Pi is incorporated into the subunit with molecular weight of 42 000. The kinase activity of the adrenal pyruvate dehydrogenase complex is high: within the first 20 sec of incubation with ATP the inactivation is as high as 60%. The pH optimum for kinase is around 7.3. The apparent Km value for ATP with 50 mM KCl is 7 microM; that in the absence of KCl is 10 microM. ADP is a competitive inhibitor of kinase with respect to ATP (Ki = 100 microM), when K+ are present in the medium. Thiamine pyrophosphate and pyruvate decrease the rate of pyruvate dehydrogenase complex inactivation. PMID- 6266521 TI - [Kinetic cooperativity of Na, K-activated adenosine triphosphatase in the brain]. PMID- 6266522 TI - A depressed patient with mild speech impediment. PMID- 6266523 TI - Glycogenolysis-induced acceleration of "de novo" purine synthesis in mouse liver. PMID- 6266524 TI - Adenylate cyclase of multiple lipomata. Regional differences in adrenaline responsiveness. AB - Multiple symmetric lipomatosis has been proposed to be associated with impaired catecholamine-responsiveness of hypertrophic adipose tissue at the level of beta adrenergic receptors or adenylate cyclase respectively. We have studied the regulation of the adenylate cyclase by guanine nucleotides and adrenaline in 5 subjects suffering from multiple encapsulated lipomata. In the presence of GTP (0.1 mmol/l) basal adenylate cyclase activity averaged 0.5 +/- 0.3 nmol cAMP/mg protein/10 minutes in normal adipose tissue and 1.0 +/- 0.4 nmol cAMP/mg protein/10 minutes in hypertrophic adipose tissue respectively. The synthetic GTP analogue GMP(PNP) (0.1 mmol/l) increased non-stimulated activity by about 100% in both tissues. Adrenaline (1 mumol/l-1 mmol/l) caused a dose-dependent increase of enzymic activity in both tissues which had a maximum of 130% above basal levels in the presence of GTP and of 300% in the presence of GMP(PNP) respectively. In one of the six subjects suffering from gluteal lipomata normal adipose tissue was obtained from the gluteal as well as the abdominal region on two occasions. Maximally effective concentrations of adrenaline (1 mmol/l) induced a 3-fold increase of enzymic activity in abdominal membranes compared with about a 1.7- and 1.75-fold increase in normal and lipomatous tissue from the gluteal region. The results show that encapsulated lipomata contain a normally reactive adenylate cyclase system. PMID- 6266525 TI - Dihydropteridine-reductase activity in breast cancer. Preliminary report. AB - The dihydropteridine-reductase activity was measured in 206 breast cancers. Large variations were found: 6% of tumors showing high values closed to those noted in liver, whereas the main group has activities of same magnitude of that in cultured fibroblasts. Significant correlation appeared between dihydropteridine reductase activities and hormonal dependence, as measured by cytosolic estrogen receptor sites. PMID- 6266526 TI - Varied magnetic field, multiple-pulse, and magic-angle spinning proton nuclear magnetic resonance study of muscle water. AB - The nuclear magnetic resonance linewidth of 1H in water of frog muscle was studied as a function of magnetic field strength and angle of orientation. The results suggest that the observed spectra are dominated by demagnetization field anisotropy and dispersion, but a small static dipolar interaction of the order of a few hertz man be present. Data from line-narrowing, multiple-pulse experiments also indicate the presence of a small dipolar broadening. PMID- 6266527 TI - Proton magnetic relaxation dispersion in solutions of the cuproprotein diamine oxidase. AB - Proton nuclear magnetic resonance relaxation measurements were made over the range 4.7--220 MHz for aqueous solutions of hog kidney diamine oxidase. The values of 1/T1 give rise in two distinct dispersions, at 16 and 75 MHz, whereas 1/T2 displays a minimum at 20 MHz. The temperature dependence of relaxation rates in all cases yield apparent activation energies less than 0.6 kcal/mol. These data indicate to us that the two Cu(II) ions of diamine oxidase are intrinsically different in terms of their electronic relaxation characteristics and hence, chemical environments. Low field limits of the two electronic relaxation times are 2 and 10 ns, with one of these correlation times being frequency dependent. The value of the frequency-dependent electronic relaxation time is governed by interactions that are modulated by a process having a correlation time of 5 ps. PMID- 6266528 TI - Light-induced interfacial potentials in photoreceptor membranes. AB - A rapid change in an interfacial electric potential of isolated bovine rod outer segment disk membranes occurs upon illumination. This potential change, which has been detected by the use of spin-labeled hydrophobic ions, apparently occurs within a low dielectric boundary region of the membrane near the external (cytoplasmic) surface and is positive with respect to the aqueous exterior of the disk. The magnitude of the potential change is pH-and temperature-dependent and appears with a first-order half-time of approximately 7 ms at 21 degrees C. A simple model in which one positive charge per bleached rhodopsin is translocated from the cytoplasmic aqueous space into the membrane low dielectric boundary region readily accounts for all experimental observations. The great similarity of the boundary potential change to the R2 phase of the early receptor potential suggests that the two have the same molecular origin. PMID- 6266529 TI - Solvent substitution as a probe of channel gating in Myxicola. Differential effects of D2O on some components of membrane conductance. AB - Careful examination of effects of solvent substitution on excitable membranes offers the theoretical possibility of identifying those aspects of the gating and translocation processes which are associated with significant changes in solvent order. Such information can then be used to develop or modify moire detailed models. We have examined the effects of heavy water substitution in Cs+-and K+ dialyzed Myxicola giant axons. At temperatures of 4-6 degrees C, the rates of Na+, K+, and Na+ inactivation during a maintained depolarization were all showed by approximately 50% in the presence of D2O. In contrast, the effects of solvent substitution on the time-course of prepulse inactivation and reactivation were much larger, with slowing averaging 160%. Studies at higher temperatures yielded Q10's for Na+ activation and K+ activation which were essentially comparable (0.72) and slightly but significantly smaller than that for inactivation during a maintained depolarization (0.84). In contrast, the Q10 for the D2O effect on prepulse inactivation was approximately 0.48. Heavy water substitution decrease Gk to a significantly greater extent than G(Na), while the decrease in the conductance of the Na+ channel caused by D2O was independent of whether the current-carrying species was Na+ or Li+. Sodium channel selectivity to the alkali metal cations and NH4+ was not changed by D2O substitution. PMID- 6266530 TI - Study of anisotropy in nuclear magnetic resonance relaxation times of water protons in skeletal muscle. AB - The anisotropy of the spin-lattice relaxation time (T1) and the spin-spin relaxation times (T2) of water protons in skeletal muscle tissue have been studied by the spin-echo technique. Both T1 and T2 have been measured for the water protons of the tibialis anterior muscle of mature male rats for theta = 0, 55, and 90 degrees, where theta is the orientation of the muscle fiber with respect to the static field. The anisotropy in T1 and T2 has been measured at temperatures of 28, -5 and -10 degrees C. No significant anisotropy was observed in the T1 of the tissue water, while an average anisotropy of approximately 5% was observed in T2 at room temperature. The average anisotropy of T2 at -5 and 10 degrees C was found to be approximately 2 and 1.3%, respectively. PMID- 6266531 TI - Interaction of barium ions with potassium channels in squid giant axons. AB - Blocking of potassium channels by internally and externally applied barium ions has been studied in squid giant axons. Internal Ba (3-5 mM) causes rapid decay or "inactivation" of potassium current (IK). The kinetics and degree of block are strongly voltage-dependent. Large positive voltages speed blocking and make it more profound. Raising the external potassium concentration (Ko) from 0 to 250 mM has the opposite effect: block is made slower and less severe. In contrast, for positive voltages block by the tetraethylammonium derivative 3 phenylpropyltriethylammonium ion is almost independent of Ko and voltage. Recovery from block by internal Ba has a rapid phase lasting a few milliseconds and a slow phase lasting approximately 5 min. Internal Ba causes a "hook" in the IK tails recorded on repolarizing the fiber in high potassium external medium. External Ba, on the other hand, blocks without much altering IK time-course. KD (the dissociation constant) for block by external Ba is a few millimolar, and depends on the internal potassium concentration, the holding potential, and other factors. A reaction scheme for Ba and K channels is presented, postulating that internal and external Ba reach the same point in the channel. Once there, Ba blocks and also stabilizes the closed conformation of the channel. The extreme stability of the Ba channel complex implies the existence of negative charge within the channel. PMID- 6266532 TI - A comparison of herpes simplex virus plaque development after viral treatment with anti-DNA or antilipid agents. AB - The plaque development of Herpes simplex virus type 1 (HSV) is slower for viruses treated with two anti-DNA agents: ultraviolet radiation (UV) or n-acetoxy-2 acetyl-aminofluorene. For HSV treated with three antimembrane agents--butylated hydroxytoluene, acridine plus near UV radiation, or ether--the plaque development time is the same as for untreated viruses. These differences hold even for viruses that survived treatment that lowered viability below the 1% level. Gamma ray inactivation of HSV produces no change in plaque development even though this agent is believed to preferentially affect viral DNA. PMID- 6266533 TI - Electric response of a back photoreaction in the bacteriorhodopsin photocycle. AB - The electric response of a back photoreaction in the bacteriorhodopsin photocycle was investigated. The proton pumping activity of green flash excited bacteriorhodopsin stops if the M412 form is illuminated by blue light (Karvaly and Dancshazy, 1977). In the present work a fast negative displacement current signal was measured in an oriented membrane suspension system, indicative of back movement of protons from M412 to BR570. Quantitative evaluation of the data shows that there are at least two steps in the back reaction, with different rate constants. The temperature dependence of the rate constants show simple linear Arrhenius behavior between 5 degree and 40 degree C. The rate constants were slower by a factor of 1.8 in D2O suspension. The relevance of the protein electric response signals (PERS) observed in this paper to the early receptor potential is discussed. PMID- 6266534 TI - Effects of the dipolar form of phloretin on potassium conductance in squid giant axons. AB - The effects of phloretin on membrane ionic conductances have been studied in the giant axon of the squid, Loligo pealei. Phloretin reversibly suppresses the potassium and sodium conductances and modifies their dependence on membrane potential (Em). Its effects on the potassium conductance (GK) are much greater than on the sodium conductance; no effects on sodium inactivation are observed. Internal perfusion of phloretin produces both greater shifts in GK(Em) and greater reductions maximum GK than does external perfusion; the effect of simultaneous internal and external perfusion is little greater than that of internal perfusion alone. Lowering the internal pH, which favors the presence of the neutral species of weakly acidic phloretin (pKa 7.4), potentiates the actions of internally perfused phloretin. Other organic cations with dipole moments similar to phloretin's have little effect on either potassium or sodium conductances in squid axons. These results can be explained by either of two mechanisms; on postulates a phloretin "receptor" near the voltage sensor component of the potassium channel which is accessible to drug molecules applied at either the outer or inner membrane surface and is much more sensitive to the neutral than the negatively charged form of the drug. The other mechanism proposes that neutral phloretin molecules are dispersed in an ordered array in the membrane interior, producing a diffuse dipole field which modifies potassium channel gating. Different experimental results support these two mechanisms, and neither hypothesis can be disproven. PMID- 6266535 TI - Interaction of nonylguanidine with the sodium channel. AB - Alkyl and aromatic guanidines interact strongly with the tetrodotoxin (TTX)- receptor site in eel electroplaque membranes, showing competition with TTX. That these guanidines could be useful as highly reversible small molecular weight blockers of Na+ currents is therefore suggested. We have investigated the mechanisms of interaction of one of these derivatives, nonylguanidine, by studying its effects on Na+ currents in squid giant axons using voltage clamp techniques. Although nonylguanidine competed with TTX for binding to eel electroplaque membrane fragments (Ki = 1.8 X 10(-5) M), it reversibly blocked both inward and outward Na+ currents in intact axons only if applied to the interior. In axons with the Na+ inactivation removed by papain nonylguanidine produced a time-dependent block very similar to that reported for strychnine and pancuronium. The reduction of steady-state currents in these axons was also voltage-dependent, with increasing block observed with increasing step depolarization. These results suggest that nonylguanidine binds to a site accessible from the axoplasmic side of the channel, simulating Na+ inactivation in papain-treated axons and competing with the normal inactivation process in untreated axons. The competition between internal nonylguanidine and external TTX may result from perturbation by the positively charged nonylguanidine of the TTX binding site from within the channel itself. PMID- 6266536 TI - Nuclear Overhauser effect and cross-relaxation rate determinations of dihedral and transannular interproton distances in the decapeptide tyrocidine A. AB - The following interproton distances are reported for the decapeptide tyrocidine A in solution: (a) r(phi) distances between NH(i) and H alpha (i), (b) r(psi) distances between NH (i + 1) and H alpha (i), (c) r(phi psi) distances between NH(i + 1) and NH(i), (d) NH in equilibrium NH transannular distances, (e) H alpha in equilibrium H alpha transannular distances, (f) r x 1 distances between H alpha and H beta protons, (g) NH(i) in equilibrium H beta (i) distances, (h) NH (i + 1) in equilibrium H beta (i) distances, (i) carboxamide-backbone protons and carboxamide-side chain proton distances, (j) side chain proton-side chain proton distances. The procedures for distance calculations were: NOE ratios and calibration distances, sigma ratios and calibration distances, and correlation times and sigma parameters. The cross-relaxation parameters were obtained from the product, say, of NOE 1 leads to 2 and the monoselective relaxation rate of proton 2; the NOEs were measured by NOE difference spectroscopy. The data are consistent with a type I beta-turn/ type II' beta-turn/ approximately antiparallel beta-pleated sheet conformation of tyrocidine A in solution and the NOEs, cross-relaxation parameters, and interproton distances serve as distinguishing criteria for beta-turn and beta-pleated sheet conformations. It should be borne in mind that measurement of only r phi and r psi distances for a decapeptide only defines the ( phi, psi)-space in terms of 4(10) possible conformations; the distances b-j served to reduce the degeneracy in possible (phi, psi)-space to one tyrocidine A conformation. The latter conformation is consistent with that derived from scalar coupling constants, hydrogen bonding studies, and proton-chromophore distance measurement, and closely resembles the conformation of gramicidin S. PMID- 6266537 TI - [1H]Spin-echo nuclear magnetic resonance in plant tissue. I. The effect of Mn(II) and water content in wheat leaves. AB - The effect of age-dependent Mn(II)-gradients, as observed by electron paramagnetic resonance (EPR), on the [1H]NMR spin-spin relaxation time (T2) was studied in wheat leaves. A non-exponential T2 spin-echo decay was always observed, revealing the presence of at least two different fractions of non- (or slowly) exchanging water in the leaves. No effect of the Mn(II)-concentration on T2 of the separate water fractions (covering approximately 90% of the total water content) has been found. From these observations we conclude that Mn(II) is present in bound form. The dependence of T2 on water content can be explained with a two-state model, demonstrating the occurrence of fast exchange within each of the two slowly exchanging water fractions. PMID- 6266538 TI - Submillisecond rotational dynamics of spin-labeled myosin heads in myofibrils. AB - The rotational motion of crossbridges, formed when myosin heads bind to actin, is an essential element of most molecular models of muscle contraction. To obtain direct information about this molecular motion, we have performed saturation transfer EPR experiments in which spin labels were selectively and rigidly attached to myosin heads in purified myosin and in glycerinated myofibrils. In synthetic myosin filaments, in the absence of actin, the spectra indicated rapid rotational motion of heads characterized by an effective correlation time of 10 microseconds. By contrast, little or no submillisecond rotational motion was observed when isolated myosin heads (subfragment-1) were attached to glass beads or to F-actin, indicating that the bond between the myosin head and actin is quite rigid on this time scale. A similar immobilization of heads was observed in spin-labeled myofibrils in rigor. Therefore, we conclude that virtually all of the myosin heads in a rigor myofibril are immobilized, apparently owing to attachment of heads to actin. Addition of ATP to myofibrils, either in the presence or absence of 0.1 mM Ca2+, produced spectra similar to those observed for myosin filaments in the absence of actin, indicating rapid submillisecond rotational motion. These results indicate that either (a) most of the myosin heads are detached at any instant in relaxed or activated myofibrils or (b) attached heads bearing the products of ATP hydrolysis rotate as rapidly as detached heads. PMID- 6266539 TI - Orientation of spin-labeled myosin heads in glycerinated muscle fibers. AB - We have used electron paramagnetic resonance (EPR) spectra to study spin labels selectively and rigidly attached to myosin heads in glycerinated rabbit psoas muscle fibers. Because the angle between the magnetic field and the principal axis of the probe determines the position of the EPR absorption line, spectra from labeled fibers oriented parallel to the magnetic field yielded directly the distribution of spin label orientations relative to the fiber axis. Two spin labels, having reactivities resembling iodoacetamide (IASL) and maleimide (MSL), were used. In rigor fibers with complete filament overlap, both labels displayed a narrow angular distribution, full width at half maximum approximately 15 degrees, centered at angles of 68 degrees (IASL) and 82 degrees (MSL). Myosin subfragments (heavy meromyosin and subfragment-1) were labeled and allowed to diffuse into fibers. The resulting spectra showed the same sharp angular distribution that was found for the labeled fibers. Thus is appears that virtually all myosin heads in a rigor fiber have the same orientation relative to the fiber axis, and this orientation is determined by the actomyosin bond. Experiments with stretched fibers indicated that the spin labels on the fraction of heads not interacting with actin filaments had a broad angular distribution. Addition of ATP to unstretched fibers under relaxing conditions produced orientational disorder, resulting in a spectrum almost indistinguishable from that of an isotropic distribution of probes. Addition of either an ATP analog (AMPPNP) or pyrophosphate produced partial disorder. That is a fraction of the probes remained sharply oriented as in rigor while a second fraction was in a disordered distribution similar to that of relaxed fibers. PMID- 6266540 TI - The electronic structure of Fe2+ in reaction centers from Rhodopseudomonas sphaeroides. I. Static magnetization measurements. AB - We have measured the static magnetization of unreduced and reduced reaction centers that vary in their quinone content. Measurements were performed in the temperature range 0.7 degrees K less than T less than 200 degrees K and magnetic fields of up to 10 kG. The electronic g-value, crystal field parameters D, E, and the exchange interaction, J, between the quinone spin and Fe2+ were determined using the spin Hamiltonian formalism. The effective moment mu eff/Fe2+ of both reduced and unreduced samples were determined to be 5.35 +/- 0.15 Bohr magnetons. This shows, in agreement with previous findings, that Fe2+ does not change its valence state when the reaction centers are reduced. Typical values of D congruent to +5 cm-1 and E/D congruent to 0.27 are consistent with Fe being in an octahedral environment with rhombic distortion. The values of D and E were approximately the same for reaction centers having one and two quinones. These findings imply that quinone is most likely not a ligand of Fe. The Fe2+ and the spin on the quinone in reduced reaction centers were found to be coupled with an exchange interaction 0 less than /J/ less than 1 cm-1. The validity of the spin Hamiltonian was checked by using an orbital Hamiltonian to calculate energy levels of the 25 states of the S = 2, L = 2 manifold and comparing the magnetization of the lowest five states with those obtained from the spin Hamiltonian. Using the orbital Hamiltonian, we calculated the position of the first excited quintet state to be 340 cm-1 above the ground state quintet. This is in good agreement with the temperature dependence of the quadrupole splitting as determined by Mossbauer spectroscopy. PMID- 6266541 TI - Unit membrane parameters of electrically syncytial tissues. AB - A change in the holding voltage, exposure to channel-blocking agents, and similar interventions will induce changes in the membrane properties of electrically syncytial tissues. The altered membrane characteristics will produce changes in the input resistance (RIN) and the phase angle (phi) of the complex admittance of the whole preparation. Exact geometry-independent formulas are derived that give the intervention-induced changes in the membrane capacitance and conductance in terms of the measured changes in RIN and phi. The formulas automatically account for the effects of extracellular resistance in tissues such as skeletal muscle fibers, cardiac Purkinje fibers, and small cardiac "aggregates." The size, shape, and resistance of the extracellular space may be arbitrary and need not be measured. The surface (invaginated) membranes, which face the bath (extracellular space), are assumed to be characterized by an RC circuit with specific capacity Cme (Cmi) and specific conductivity gme (gmi). It is assumed that the intracellular voltage gradient between the electrodes and the membranes is negligible or reliably calculable. The intervention is assumed to leave the geometry and resistivity of the extracellular space unchanged. Under these circumstances the intervention-induced changes in Cme, Cmi, gme, and gmi are determined exactly in terms of the corresponding changes in RIN and certain frequency domain integrals over phi. The technique is illustrated by synthetic data for RIN and phi generated by the "disk" model of a skeletal muscle fiber in which Cme and Cmi depend upon holding voltage. The corresponding voltage dependence of RIN and phi is successfully "inverted" to expose the underlying voltage dependence of Cme and Cmi. These computations suggest that the formulas for Cme and Cmi will be useful in realistic situations, since they are not too sensitive to experimental error in the data for RIN and phi. This method makes it possible to detect voltage-dependent capacity changes due to unit membrane processes (e.g., charge movement) as long as the intrinsic time constant of that process is very small (e.g., less than 1/30 ms). As a second example I consider a disk model that is exposed to increasing concentrations of a channel-blocking agent. The drug dependence of RIN and phi is used to calculate the drug dependence of the total membrane conductivity (the sum of gme and gmi, weighted by the areas of surface and invaginated membranes, respectively). PMID- 6266542 TI - Material from the internal surface of squid axon exhibits excess noise. Implications in modeling membrane noise. AB - A fluid material from a squid (Loligo pealei) axon was isolated by mechanical application of two types of microcapillary (1-3-mum Diam) to the internal surface of intact and cut-axon preparations. Current noise in the isolated material exceeded thermal levels and power spectra were 1/f in form in the frequency range 1.25-500 Hz with voltage-dependent intensities that were unrelated to specific ion channels. Whether conduction in this material is a significant source of excess noise during axon conduction remains to be determined. Nevertheless, a source of excess noise external to or within an ion channel may not be properly represented solely as an additive term to the spectrum of ion channel noise; a deconvolution of these spectral components may be required for modeling purposes. PMID- 6266543 TI - Block and inactivation of sodium channels in nerve by amino acid derivatives. I. Dependence on voltage and sodium concentration. AB - The side chain of arginine, n-propylguanidinium (nPG), reversibly decreases peak sodium conductance and increases the speed of sodium current decay, when perfused internally. Effects are voltage dependent and are more pronounced at high depolarizations. Results are also dependent on the sodium concentration gradient. Both the decline in peak conductance and the speeding of inactivation are greater if the sodium concentration gradient is reversed from the normal. The decrease in peak sodium current is too large to be due solely to the faster decay kinetics. The difference is not due to a change in slow inactivation of the channel. Sodium current inactivation has also been studied with a double pulse procedure. Results show that at - 70 mV, nPG leaves sodium channels rapidly (less than 500 microseconds) in normal sodium gradient, but more slowly (greater than 1 ms) in reversed sodium gradient. Several structural analogs of nPG have been tested. Shortening the alkyl chain weakens effects significantly. Arginine itself, which contains extra charged groups, is also less effective. n-Propylammonium is active but with an apparent affinity only one-fifth that of arginine. We conclude that nPG acts within the sodium channel, and has at least two modes of action. PMID- 6266545 TI - Molecular dynamics study of ion transport in transmembrane protein channels. AB - Ion transport through biological membranes often takes place via pore-like protein channels. The elementary process of this transport can be described as a motion of the ion in a quasi-periodic multi-well potential. In this study molecular dynamics simulations of ion transport in a model channel were performed in order to test the validity of reaction-rate theory for this process. The channel is modelled as a hexagonal helix of infinite length, and the ligand groups interacting with the ion are represented by dipoles lining the central hole of the channel. The dipoles interact electrostatically with each other and are allowed to oscillate around an equilibrium orientation. The coupled equations of motion for the ion and the dipoles were solved simultaneously with the aid of a numerical integration procedure. From the calculated ion trajectories it is seen that, particularly at low temperatures, the ion oscillates back and forth in the trapping site many times before it leaves the site and jumps over the barrier. The observed oscillation frequency was found to be virtually temperature independent (nu 0 approximately equal to 2 X 10(12) s-1) so that the strong increase of transport rate with temperature results almost exclusively from the Arrhenius-type exponential dependence of jump probability w on 1/T. At higher temperatures simultaneous jumps over several barriers occasionally occur. Although the exponential form of w(T) was in agreement with the predictions of rate theory, the activation energy Ea as determined from w(T) was different from the barrier height which was calculated from the static potential of the ion in the channel; the actual transport rate was 1 X 10(3) times higher than the rate predicted from the calculated barrier height. This observation was interpreted by the notion that ion transport in the channel is strongly influenced by thermal fluctuations in the conformation of the ligand system which in turn give rise to fluctuations of barrier height. PMID- 6266544 TI - Block and inactivation of sodium channels in nerve by amino acid derivatives. II. Dependence on temperature and drug concentration. AB - The interaction of n-propylguanidinium (nPG) with sodium channels has been further characterized. From experiments at varying temperatures, the Q10 for the sodium current decay time constant in the two [Na+] gradients is 2.6-2.9 independent of drug. Testing several nPG concentrations we find that peak sodium current declines sharply with [nPG] at all levels, but the decay time constant approaches an asymptote above 4 mM. No "hooks" in sodium tail currents are seen. If the sodium current is allowed to decay completely before repolarization no tail current is observed. We have developed a kinetic model in which nPG acts at a single site within the sodium channel. Reaction of nPG with its receptor requires two steps. Fitting the temperature data shows that the first step involves diffusion of the drug to the site and close association with it. The second step may include molecular reorganization of the complex. The rate constants for the reaction are all simple exponential functions of voltage. Using them, the model successfully predicts decay time constants and peak currents, and their dependence on potential, [Na+] gradient, temperature, and nPG concentration. The results are consistent with the idea that an arginine residue may be closely associated with inactivation. PMID- 6266547 TI - [Role of cAMP in the mechanism of the fever reaction]. AB - It has been shown that accumulation of endogenous cAMP caused by theophylline increases the body sensitivity to the minimum doses of leukocytic and bacterial pyrogens and to prostaglandin E1. The increasing effect of theophylline was abolished by administering the higher doses of the pyrogenic agents. Repeated daily administration of bacterial pyrogen in conjunction with theophylline does not induce the development of tolerance. The possible reasons for enhanced fever in response to the minimum doses of the pyrogenic agents during accumulation of endogenous cAMP are discussed. PMID- 6266546 TI - [Effect of hypoxia and fenigidin on the action potential duration and the strength of myocardial contraction in frogs]. AB - A 40-minute perfusion of the frog ventricular strip with a hypoxic Ringer solution brings about a decline in action potential duration by 37 plus or minus 10% whereas the contractility is completely suppressed by that time. The time constant of the contractility exponential decline constitutes 8 plus or minus 2 min. the effect of hypoxia is reversible. Complete blockade of the calcium channels by fenigidin (3.5 x 10(-5) M) irreversibly lowers action potential duration by 62 plus or minus 2%. Contraction is completely suppressed on attaining the given level of action potentials. Hypoxia does not virtually affect action potential after the preliminary blockade of the calcium channels by fenigidin. It is suggested that the hypoxic solution mainly blocks the inward current across the calcium channels without affecting the potassium permeability of the sarcolemma. Meanwhile complete suppression of the contractility under hypoxia cannot be accounted for only by the blockade of the calcium channels. PMID- 6266548 TI - [Adrenoreceptor-independent effect of thyroxine and adrenoxyl on myocardial adenyl cyclase activity and cAMP levels]. AB - A study was made of the effect of different concentrations of noradrenaline, adrenaline, adrenoxyl (stabilized adrenochrome) and thyroxin on the adenylate cyclase activity and cAMP content in the myocardium of intact animals and in neurogenous affections of the myocardium. It was shown that the content of cAMP in the myocardium drops in neurogenous affections and that thyroxin or adrenoxyl in combination with beta-adrenoblockers (propranolol) might be used for the recovery of the cAMP content and adenylate cyclase activity. PMID- 6266549 TI - [Effect of pituitary hormones on phosphodiesterase and adenyl cyclase activity of brain tissue in vitro]. AB - Effects of seiwhale somatotropin (STH), its biologically active fragment 77--107, porcine corticotropin (ACTH) and seiwhale prolactin on phosphodiesterase and adenylate cyclase activity of glial cells and synaptosomes isolated from the rat brain cortex were investigated. As compared with control, ACTH increased phosphodiesterase activity of glial cells by 392%, of synaptosomes by 123%, while STH by 49 and 77%, respectively, somatotropin fragment by 455 and 74%, and prolactin by 30 and 37%, respectively. Adenylate cyclase activity was significantly changed only by ACTH and only in synaptosomes (a 50% decrease). STH, its fragment and prolactin virtually failed to alter adenylate cyclase activity. The data obtained indicate that some of pituitary hormones, primarily ACTH and STH, may play the role of neuromodulators in some brain structures by decreasing the cyclic AMP level, by activating phosphodiesterase (STH and ACTH) and inhibiting adenylate cyclase (ACTH in synaptosomes). PMID- 6266550 TI - [DNA-ase I activity in the DNA-ase I-inhibitor system]. AB - An increase in the DNase I activity was revealed in the serum of mice after intraperitoneal injection of different antigens. This reaction is related to the antigen nature and is dissimilar in mice of different strains. The increased activity of the inhibitor in the spleen of DBA/2 and BALB/c mice was discovered after intravenous injection of bovine DNase I. A potential role of serum DNase I in the system DNase I-inhibitor is discussed. PMID- 6266551 TI - [Effect of administration of ampiox and guanosine triphosphate on the concentration of cyclic nucleotides in the muscle tissue of a zone of inflammation]. AB - Experiments on rabbits with infiltrates induced by intracutaneous injection of staphylococcal culture were made to examine the content of cyclic nucleotides in the adjacent muscle tissue under the effect of administering ampiox alone or combined with guanosine triphosphate (GTP). Combined injection of ampiox and GTP to the infected animals produced a considerable elevation in the content of cAMP (more than 2 1/2-fold) and in the cAMP/cGMP ratio along with a beneficial therapeutic effect. The possible mechanisms of action of the agents administered are discussed. PMID- 6266552 TI - [Enkephalins and gastrin fragments: possible existence of different analgesic mechanisms]. AB - The mechanism of analgetic action of pentagastrin, its tripeptide fragment (MAF), synthetic met- and leu-enkephalins was studied in rats. The analgetic effect of the peptides was evaluated from the tail extracting test. Also, the content of biogenic amines in the rat brain and interaction of the peptides with opiate receptors of the guinea-pig ileum were examined. It was demonstrated that analgesia induced by pentagastrin or MAF differs from that obtained after intraventricular injection of the enkephalins. The effect of the latter ones is not consequent on their interaction with classic opiate receptors. It was also discovered that pentagastrin, MAF and enkephalins produce a different action on metabolism of biogenic amines. The possibility of analgesia unmediated by specific peptide binding to opiate receptors is discussed. PMID- 6266553 TI - [ATP-ase and 5'-nucleotidase activity of the nuclear matrix of the rat liver]. PMID- 6266554 TI - [Cell membrane mechanism of action of prostaglandins E1 and F2 alpha on thrombocyte function]. AB - PGE1 and PGF2 alpha were shown to exert an opposite action on Na, K-ATPase activity and protein fluorescence of the platelet membranes. The effect of the prostaglandins appeared to be unidirectional as regards the erythrocytic membranes. The prostaglandins were demonstrated to increase viscosity of the lipid bilayer and its permeability by uni- and bivalent cations. PMID- 6266555 TI - [Mechanism of the relaxant action of noradrenaline on coronary artery smooth muscle cells]. AB - Electrical and contractile activity of smooth muscle cells (SMC) of bovine coronary arteries was examined by the double sucrose gap method. It was shown that, on the one hand, noradrenaline increased the potassium membrane permeability followed by hyperpolarization which led to the closing of potential dependent show calcium channels and to the reduction of the transmembrane calcium ion influx. On the other hand, noradrenaline closed potential-dependent chemosensitive calcium channels that limited influx of extracellular calcium ions into SMC. Such a double-noradrenaline effect resulted in a considerable decrease of the concentration of intracellular calcium ions and in the falling of the basal tone of arterial SMC. PMID- 6266557 TI - [Certain mechanisms of the effect of EDTA on thrombocyte aggregation]. AB - Effect of EDTA on the ADP-induced platelet aggregation and intraplatelet regulatory mechanisms were examined. EDTA (and EGTA) was shown to inhibit platelet aggregation and to potentiate the similar effect of theophylline and dibutyryl cAMP. Inhibition of platelet aggregation was seen during incubation of EDTA in conjunction with dibutyryl cAMP at concentrations that did not change the platelet aggregation profile provided the agents cited were incubated alone. Verapamil and tetracain potentiated the inhibitory effect on aggregation of EDTA, dibutyryl cAMP and EDTA plus dibutyryl cAMP. PMID- 6266556 TI - [Therapeutic effect of a saline solution with sodium lactate (lactasol) in traumatic shock]. AB - Acute experiments on 67 adult dogs have demonstrated that infusions of lactasol in a dose of 25 ml/kg in the early period and in a dose of 50 ml/kg in the late period of shock are not efficacious enough. Injection of the increased amount of the saline in the early and late period of shock (up to 50 and up to 100 ml/kg, respectively) makes it possible to save from death almost all the animals. A conclusion is made that the therapeutic effect of lactasol depends on the amount of the saline injected and on the period of shock during which the saline is injected, as well as on the specific action of sodium lactate. PMID- 6266558 TI - [Quantity of exogenous linear DNA absorbed by E. coli cells treated with Ca2+ cations]. AB - The amount of linear chromosomal DNA entering Ca2+-treated Escherichia coli K 12 cells was estimated from the degree of degradation of exogenous DNA by intracellular nucleases. At least 40% of DNA adsorbed by the cells in the nucleaso-resistant form (45 MD/cell) was discovered to be as intracellular. No significant difference was found between single- and double-stranded DNA. PMID- 6266559 TI - [Rosette-forming ability of virus-treated human leukocytes (V-rosettes)]. AB - Rosette-formation with auto- and allogeneic red blood cells was applied to detection of human leucocyte subpopulations interacting with Sendai virus (V rosettes). It was shown that the majority of V-rosette-forming cells appeared to be monocytes. T lymphocytes did not take part in V-rosette-formation since selective elimination of T cells from the mononuclear cells population did not lead to reduction of but increased the number of V-rosettes. Enrichment of cell suspension with B lymphocytes was followed by a rise in the number of V-rosettes thereby allowing the attribution of B lymphocytes along with monocytes to the cell population interacting with virus. The results suggest that ability of virus exposed immunocompetent cells to react with their own red blood cells may lie at the basis of the development of autoimmune hemolytic anemia and other autoimmune diseases. PMID- 6266560 TI - [Effect of 5'-deoxy-5'-S-isobutyladenosine on hematopoietic stem cells]. AB - Unlike known cytostatics, 5'-deoxy-5'-S-isobutyladenosine (SIBA) does not inhibit proliferative activity of hemopoietic stem cells of intact bone marrow. On the contrary, it raises CFUs number of 15-28% in vitro and in vivo. SIBA inhibits by 40% the 3',5'-cAMP-induced increase in CFUs proliferation. PMID- 6266561 TI - [Ring-shaped inclusions in an uncommon variety of acute myeloid leukemia (author's transl)]. AB - In cells of an acute, predominantly promyelocytic differentiated leukemia ring shaped inclusions could be demonstrated by light- and electron-microscopic examinations. The patient showed good response to aggressive chemotherapy with complete remission. It is discussed, how far the presence of these morphological characteristics will have any bearing on the classification of this variety of leukemia. PMID- 6266563 TI - Review of the pharmacology of khat. Report of a WHO advisory group. PMID- 6266562 TI - Auer bodies in acute lymphocytic leukaemia and B-cell lymphoma: evidence for a common progenitor of myeloid and lymphoid cells? AB - In a patient with acute lymphocytic leukaemia (pre-T ALL) and another patient with leukaemic generalization of B-cell lymphoma Auer bodies were found in a few immature cells. The diagnosis in both cases was based on clinical grounds, morphology, cytochemistry, and immunological marker analysis of the blasts. Auer bodies are known to be a marker of high significance for acute non-lymphocytic leukaemias. Therefore the findings described suggest mixed leukaemias with either T-cell or B-cell predominance. It provides further evidence for the existence of a common progenitor of myeloid and lymphoid cells. PMID- 6266564 TI - Activity of cannabis in relation to its delta'-trans-tetrahydro-cannabinol content. AB - 1 Conditions have been worked out for a reliable estimation of the cataleptic activity of delta'-trans-tetrahydrocannabinol (THC) after oral administration to mice, using the ring test over a period of 6 h. 2 By this method, the activity of cannabis herb and 5 crude fractions were measured against THC; at the same time the THC contents were determined chemically. 3 The B/C ratio (biological activity divided by chemical assay) was calculated for each. With cannabis herb the value was 3.3 and with extracts prepared with ethanol or 70% ethanol the values ranged from 3.2 to 7.1, indicating that in all samples the activity was much higher than would be expected from their THC content. 4. The cannabinoids were completely extracted from a sample of herb using petroleum spirit and the marc examined for a possible synergist. Surprisingly, it contained a powerful inhibitor of the action of THC, which could be restored by intraperitoneal prostaglandin E2 (3 microgram/kg). Some crude fractions had inhibitory activities about 10 times that of aspirin. 5 In contrast, the petroleum spirit extract (referred to in 4) had a surprisingly high B/C ratio of 23, indicating that a powerful synergist of THC activity is present. 6 The net effect of the herb and ethanol extracts is probably due to a balance of synergist and inhibitor. PMID- 6266565 TI - The binding of [3H]-prostacyclin to membranes of a neuronal somatic hybrid. AB - 1 [3H]-prostacyclin bound to a washed membrane preparation of the NCB-20 neuronal hybrid cell line. 2 Kinetic analysis of [3H]-prostacyclin binding suggested a simple, non-cooperative bimolecular interaction between the ligand and a single receptor population. The equilibrium dissociation constant was 16.6 nM, and binding at a saturating [3H]-prostacyclin concentration enabled the receptor density of 2.57 x 10(5) receptor molecules per cell to be calculated. 3 At 20 degrees C the rate constant for the forward reaction (K+1) was 2.26 x 10(5) M-1 S 1, and the rate constant for the dissociation of the ligand-receptor complex (k 1) was 3.85 x 10(-3) S-1. Thus the dissociation constant (k-1/k+1) was 17.0 nM. 4 Prostaglandin E1 and prostacyclin compete for a single receptor in these cells, and comparison of other prostaglandins as inhibitors of [3H]-prostacyclin binding revealed some of the structural requirements for high-affinity occupation of prostacyclin receptors. PMID- 6266566 TI - Enkephalin receptors in the emetic chemoreceptor trigger zone of the dog. AB - 1 The emetic action of Met-enkephalin, morphine and naloxone was studied following their administration into the cerebral ventricles of dogs through chronically implanted cannulae and the effect on the responses of ablating the chemorceptor trigger zone (CTZ) was investigated. The opiate antagonist, naloxone, was used to determine the role of enkephalin receptors in emetic responses.2 Administration of Met-enkephalin (1.0 mug/kg) into the IVth ventricle regularly evoked emesis with an average latency of 35 s. A dose of morphine (2.5 mug/kg) which was five times larger was required for a consistent emetic response when introduced into the lateral cerebral ventricle (i.c.v.) as compared to the dose required by the IVth ventricular route. The latency of emetic responses by the latter route of injection of morphine was shorter. This is in accord with an action of morphine on the emetic CTZ.3 After bilateral ablation of the CTZ, intraventricular injections of Met-enkephalin and morphine failed to produce emesis even when given in doses that were 5 to 10 times the dose which regularly elicited emesis in animals with intact CTZ. The emesis produced in dogs by intraventricular Met-enkephalin and morphine is thus fully accounted for by an action on the CTZ.4 Naloxone (i.c.v.) in doses up to 10.0 mug/kg did not cause emesis. However, higher doses of naloxone elicited dose-dependent emesis in dogs. The 100% emetic dose of naloxone was found to be 160 mug/kg and the latency of emesis was 180 s. Unlike Met-enkephalin and morphine, naloxone continued to elicit emesis in CTZ-ablated animals.5 Pretreatment with intraventricular naloxone (1 to 8 mug/kg) blocked the emetic responses induced by intraventricular Met-enkephalin and morphine but not that to apomorphine. The selective protective action of the opiate antagonist against Met-enkephalin and morphine supports the presence of enkephalin receptors in the emetic CTZ. PMID- 6266568 TI - Carcinogenesis and mineral fibres. PMID- 6266567 TI - Leukotriene B4: a mediator of vascular permeability. AB - 1 Intradermal injection of leukotriene B4 (LTB4) or prostaglandin E2 (PGE2), 1 to 100 ng per skin site produced little or no change in plasma exudation in the rabbit, guinea-pig and rat. 2 Intradermal injection of LTB4 or PGE2 together with bradykinin (500 ng) resulted in a significant potentiation of the plasma exudation produced by bradykinin alone in the rabbit and guinea-pig. 4 LTB4 (1 to 10 ng) had no effect on blood flow in the rabbit skin, in contrast to PGE2 which was a potent vasodilator in this species. 5 It is concluded that LTB4 is a mediator of vascular permeability and that this effect can only be observed in the presence of a vasodilator such as PGE2. PMID- 6266570 TI - Electrodiagnosis of the muscular dystrophies. PMID- 6266569 TI - Bracken fern and papilloma virus in bovine alimentary cancer. PMID- 6266571 TI - Muscle cell differentiation and the prospects for genetic engineering. PMID- 6266572 TI - Is there a membrane defect in muscle and other cells? PMID- 6266574 TI - Are fibre supplements really necessary in diverticular disease. PMID- 6266573 TI - Dietary fibre. PMID- 6266575 TI - Prevention of haemolytic disease of the newborn due to anti-D. PMID- 6266577 TI - Isolation of Bordetella pertussis from swabs. AB - Four varieties of swabs held in plastic containers and three swab transport media kits, all obtainable in the United Kingdom, were tested to assess their effectiveness in the isolation of Bordetella pertussis. The highest isolation rates up to 48 hours were obtained with Dacron swabs held in plastic containers. Swab-transport media kits proved unsatisfactory. B pertussis may have a stronger affinity to Dacron than to cotton-wool, and pernasal swabs should be made of Dacron to improve the recovery of B pertussis. PMID- 6266576 TI - Non-sulfhydryl-containing angiotensin-converting enzyme inhibitor (MK421): evidence for role of renin system in normotensive subjects. AB - A non-sulfhydryl-containing inhibitor of angiotensin-converting enzyme (MK421) was given as a single dose in a randomised double-blind cross-over trial using 20 mg and 5 mg of MK-421 or matched placebo to nine normotensive volunteers receiving a sodium intake of 150 mmol (mEq) daily. The two dosages of MK-421 caused similar, significant falls in supine and standing blood pressure, which were maximum four to six hours after dosing (9.5-11.0% fall). With this fall in blood pressure there was a significant fall in activity of angiotensin-converting enzyme and in concentrations of plasma angiotensin II and aldosterone and a rise in plasma renin activity. Placebo caused no significant change in blood pressure or blood measurements. The study showed that MK-421 inhibits angiotensin converting enzyme activity and lowers blood pressure in normotensive subjects. It strongly suggested that the renin system plays an important part in maintaining blood pressure in normotensive subjects receiving normal sodium intake. The results also suggest that this non-sulfhydryl-containing converting-enzyme inhibitor will be an effective blood-pressure-lowering drug in patients with blood pressure. A single dose of 5 mg was as effective at lowering blood pressure as a single dose of 20 mg. PMID- 6266578 TI - Poliomyelitis serosurveillance in adolescent population. PMID- 6266579 TI - Muscarinic-dopaminergic synergism on retinal cyclic AMP formation. AB - The cholinergic agonist, carbachol, produces a small increase in cyclic AMP concentration in the isolated rat retina, and markedly potentiates dopamine stimulated cyclic AMP formation. This effect of carbachol is mediated through a muscarinic receptor, is calcium-independent, and is not due to inhibition of phosphodiesterase activity. Activation of muscarinic receptors may potentiate dopaminergic responses in the retina by enhancing coupling of the dopamine receptor to adenylate cyclase. PMID- 6266580 TI - Increased GABA binding in mouse brain following acute swim stress. AB - Acute swim stress of mice produces increases in the density of high and low affinity binding sites in the brain for the inhibitory neurotransmitter gamma aminobutyric acid (GABA), together with analgesia as measured by an increase in tail flick latency. Apparent tolerance develops in repeated swimming with analgesia and GABA binding returning towards control levels. The time course of analgesia and increases GABA binding following a single swim are also similar. Acute swim stress does not alter diazepam binding. GABA systems may be important in analgesia and in responses to environmental stress. PMID- 6266581 TI - Two types of potassium channels in the PC12 cell line. AB - Activation of K+ channels in the PC12 cell line was studied by comparing 86Rb+ efflux under depolarizing and non-depolarizing conditions. Evidence for both Ca2+ dependent and voltage-dependent K+ channels was obtained by studying depolarization-induced 86Rb+ efflux in solutions of varying Ca2+ concentration and in the presence of K+ and Ca2+ channel blocking agents. PMID- 6266582 TI - Suppressive influences from periaqueductal gray and nucleus raphe magnus on respiration and related reflex activities and on solitary tract neurons, and effect of naloxone. AB - Possible opiate-related descending influences from the periaqueductal gray matter (PAG) and nucleus raphe magnus (NRM) were tested on the activity of neural systems involved in respiration and related reflex functions in cats. Stimulation of PAG and NRM could powerfully suppress the simple buccopharyngeal reflexes of jaw-opening and tongue-protrusion and the more complex reflexes of coughing and swallowing; respiration in contrast appeared to be only weakly influenced. The reflexly induced responses of 57 single reflex interneurons recorded in the solitary tract nucleus (NST) could also be markedly suppressed by PAG and NRM conditioning stimulation. In contrast, the rhythmic activity of 30 respiratory neurons in NST was not abolished by PAG and NRM stimuli but most did show a decrease in the peak firing frequency of each rhythmic burst. The suppressive effect of PAG and NRM stimulation on the reflexes and NST reflex interneurons could be reduced by the intravenous administration of naloxone. These studies indicate that neuronal functions associated with respiration and respiratory related activities can be suppressed by descending influences from PAG and NRM that are in part opiate-related. The observations add to the accumulating evidence that the raphe system is implicated in functions other than pain and its control, and they may also be relevant to clinical observations of opiate-induced effects on respiration and the cough reflex. PMID- 6266583 TI - Heart rate conditioning in the pigeon immobilized with alpha-bungarotoxin. AB - Previous in vitro studies have yielded conflicting results concerning the physiological effects of alpha-bungarotoxin (alpha-BTX) at avian autonomic ganglia. In the present study heart rate change was classically conditioned in pigeons immobilized with alpha-BTX to assess the effects of this agent on autonomic function in the intact animal. When compared with non-immobilized controls, alpha-BTX had no significant effect on basal heart rate or on the rate of acquisition, magnitude or dynamics of conditioned heart rate change. Furthermore, a significant difference in performance between groups receiving conditioning and sensitization paradigms clearly indicated the establishment of conditioned responding. It is concluded that alpha-BTX has little or no effect on the cardiac innervation at doses sufficient to block neuromuscular transmission. The irreversible blockade of neuromuscular transmission by alpha-BTX without the side-effects produced by most other paralytics makes it an ideal choice as an immobilizing agent in acute preparations. PMID- 6266584 TI - Lamellar bodies in Purkinje nerve cells experimentally induced by electric field. AB - Rabbits reared from mating to the age of almost two months outdoors in a substation in an electric (E)-field of 14 kV/m (undisturbed field, 50 Hz AC) only gained about half the weight of their controls, either protected by a Faraday's cage or being kept outside measurable E-field. The Purkinje nerve cells of cerebellum showed important alterations of the endoplasmic reticulum with disintegration of Nissl bodies, disappearance of hypolemmal cisterns and formation of numerous lamellar bodies. Concomitantly, there was a reduction in number of microtubules and increase in neurofilaments. These structural neuronal changes were reflected by changes in the behaviour of the rabbits which become slow in movements. PMID- 6266585 TI - Micromolar L-2-amino-4-phosphonobutyric acid selectively inhibits perforant path synapses from lateral entorhinal cortex. AB - Transverse slices of the rat hippocampus were used to examine the ability of phosphonate analogues of acidic amino acids to inhibit perforant path synaptic transmission. Micromolar concentrations of L-2-amino-4-phosphonobutyric acid (APB), an analogue of L-glutamic acid, inhibited transmission from the lateral entorhinal cortex. Two other less-sensitive components were detected in projections from the medial entorhinal cortex. The component from the lateral entorhinal cortex showed high stereospecificity for the L-isomer of APB and was relatively insensitive to phosphonate homologues of shorter and longer chain length. PMID- 6266586 TI - Control of the variability of the afferent discharge rate in frog muscle spindle by potassium blockers. AB - Blockage of the K+ channels in the sensory terminal of frog muscle spindle by the combined application of BaCl2 and other K+ blockers makes it possible to reversibly change the sustained and irregular discharges into non-sustained regular discharges. As a similar change in the discharge pattern is also made by application of CoCl2 alone, though it is irreversible, the irregular and sustained discharge may be due to [Ca2+]i-activated potassium conductance. PMID- 6266587 TI - Benzodiazepine and GABA receptors in the rat retina: effect of light and dark adaptation. PMID- 6266588 TI - beta 1-adrenergic receptors in human neuroblastoma. PMID- 6266589 TI - Cervical input to vestibulocollic neurons. AB - Extracellular responses of vestibulospinal neurons projecting to neck segments (vestibulocollic neurons) to stimulation of cervical afferents were studied in decerebellate cats anesthetized with chloralose or decerebrated intercollicularly. These neurons were antidromically activated by microstimulation in the C2 ventral horn ipsilateral or contralateral to the vestibular nuclei. Contralateral neck afferents produce in vestibulocollic neurons the same responses they produce in other vestibulo-spinal neurons, although the response (early excitation, inhibition) which predominates varies with type of preparation. In intercollicular decerebrate cats, the main effect of stimulating the contralateral C2 ganglion was inhibition (latency greater than or equal to 6 msec), often followed by late excitation. Early excitation, at a latency less than 6 msec, was rarely seen, although it occurred in half the vestibulospinal neurons projecting to the cervical enlargement. In contrast to the results in decerebrate cats, stimulation of the contralateral C2 ganglion produced early excitation in over one-third of the vestibulocollic neurons studied in chloralose-anesthetized cats. Results on vestibulocollic neurons were similar whether the cells projected ipsilaterally or contralaterally, or whether or not the cells also projected to the cervical enlargement (branching neurons). The influence of cervical afferents on vestibulocollic neurons demonstrates supraspinal paths by which cervical afferents may act upon the neck and might modify vestibular reflexes of the neck. PMID- 6266590 TI - Antagonism of the baroreceptor reflex by glutamate diethyl ester, an antagonist to L-glutamate. AB - Recent reports have suggested that the excitatory amino acid L-glutamate is a neurotransmitter released by baroreceptor afferent nerves at their termination in the nucleus tractus solitarii (NTS). In this study we have examined the effect on arterial pressure, heart rate and baroreflex activity of the glutamate antagonist glutamate diethyl ester (GDEE) microinjected into the NTS of 50 rats anesthetized with Chloralose. Bilateral injections of GDEE produced dose dependent transient hypertension. The threshold dose was 2.5 micrograms/NTS and at a dose of 15 micrograms/NTS a maximal rise in arterial pressure and heart rate (from 95 +/- 8.7 mm Hg to 153 +/- 6.4 mm Hg and from 322 +/- 14.7 beats/min to 364 +/- 16.2 beats/min respectively, P less than 0.001, n = 6) occurred. A dose of 15 micrograms/NTS also completely blocked the baroreflex when injections were made bilaterally and it totally antagonized the cardiovascular effects of L-glutamate when injected immediately prior to L-glutamate. The hypertension, the antagonism of L-glutamate, and the blockade of the baroreflex persisted for 20-30 min. In that L-glutamate mediates a baroreflex-like response upon injection into NTS and in that GDEE blocks that response while at the same time blocking the naturally occurring baroreflex, the data are consistent with L-glutamate being a neurotransmitter of baroreflex afferents. PMID- 6266591 TI - Development of acute tolerance during exposure of hippocampal explants to an opioid peptide. AB - Bath application of FK 33-824, a stable enkephalin analogue, altered synaptic potentials and induced sustained depolarization shifts in hippocampal pyramidal cells. In a proportion of cells, these excitatory effects diminished and then disappeared within 6-8 min during FK 33-824 perfusion. This desensitization was temperature-sensitive. In contrast, no desensitization to similar excitatory effects of bicuculline was seen after acute application. This GABA-antagonist also excited cells which first had been rendered tolerant to the action of FK 33 824, but cross-tolerance occurred between FK 33-824 and (D-Ala)2-(D-Leu)5 enkephalin. PMID- 6266592 TI - Relationship between two voltage-dependent serotonin responses of molluscan neurones. AB - A serotonin (5-HT)-induced slow inward current was reanalyzed in identified snail neurones and found to result from a decrease in a voltage-dependent K+ conductance, sensitive to [Ca2+]0 changes. 5-HT evoked in the same neurones an increase in the spike plateau known to be associated to a K+-conductance decrease. Both 5-HT responses appear to reflect the same decrease in K+ conductance. PMID- 6266593 TI - Ethyl beta-carboline-3-carboxylate antagonizes the action of GABA and benzodiazepines in the hippocampus. AB - In urethane-anaesthetized rats, the beta-carboline derivative beta CCE (0.3-1.0 mg/kg i.v.) excited hippocampal pyramidal cells which were inhibited by GABA (applied iontophoretically) and benzodiazepines (applied iontophoretically or intravenously). While benzodiazepines facilitated the action of GABA, the effects of GABA and benzodiazepines were antagonized by beta CCE. This electrophysiological study supports the behavioural observations that beta CCE is a benzodiazepine receptor antagonist. PMID- 6266594 TI - Modulation of slow postsynaptic potentials by dopamine, in rabbit sympathetic ganglion. AB - (1) Temporary exposure of rabbit's superior cervical ganglion (SCG) to dopamine (DA), in the presence of an inhibitor of catechol-o-methyltransferase (COMT) is consistently followed by a potentiation of the slow (s)-EPSP and s-IPSP, lasting for some hours. The fast (f)-EPSP is not significantly increased, but it is better maintained than in control ganglia. (2) Exposure to the COMT-inhibitor U 0521 alone induces less but substantial potentiations of both s-PSPs. This effect is explained as due to protection of DA released intraganglionically at rest. (3) This evidence suggests that COMT may significantly limit the access of catecholamines to postsynaptic receptors, for at least certain types of neuron-to neuron synaptic actions. (4) The potentiation of both s-PSPs, whether induced by DA in the presence of U-0521 or by U-0521 alone, is depressed by DA-1 antagonists that have been found to depress DA-stimulation of adenyl cyclase in rabbit SCG; these are spiroperidol, butaclamol and, to a lesser extent, bromocriptine. The specific 'DA-2' antagonists metoclopramide and sulpiride, and the alpha adrenergic antagonist dihydroergotamine, did not depress potentiation. (5) Potentiation of s-EPSP is viewed as identical in nature to the previously discovered DA-modulatory enhancement of direct muscarinic depolarizing actions (by acetylcholine or its agonists). Potentiation of s-IPSP may be due to a similar DA-modulation of other muscarinic response(s) involved in mediating the s IPSP. The consistency and comparative ease with which these DA-modulatory effects can be induced, under presently described experimental conditions, should facilitate future study of this mode of synaptic action. PMID- 6266596 TI - Pineal protein synthesis highly sensitive to ACTH-like neuropeptides. AB - Pineal protein synthesis was studied in vitro over a period of 6-8 h after dissection. The level of protein synthetic activity of the pineal gland was greatly dependent on the time of dissection showing a maximum at midnight and a minimum at 10.00 h, 2 h after onset of light. Low concentrations of ACTH1-24 (down to 10(-11) M) could stimulate protein synthesis in vitro. The sensitivity to hormonal stimulation showed a circadian variation similar to that observed in the basal protein synthetic activity. Furthermore, overall synthetic activity appeared to be under neural influence. These neural and hormonal influences seemed to be mediated by beta-receptor stimulation and cyclic AMP. Structure activity studies of the ACTH-effect on pineal protein synthesis gave results similar to those previously observed for excessive grooming behaviour, synaptic plasma membrane phosphorylation, adenylcyclase-activity and cell-free protein synthesis in brain. It was concluded, that overall pineal protein synthesis is both under neural and hormonal control. The action of ACTH on protein synthesis rate might be mediated by a calcium-dependent release of norepinephrine followed postsynaptically by beta-receptor activation, cAMP production, and stimulation of translation. PMID- 6266595 TI - Presynaptic alpha-adrenergic mediation of self-stimulation in locus coeruleus in rats treated neonatally with 6-hydroxydopamine. AB - Rats self-stimulating in the region of the locus coeruleus and treated neonatally with 6-hydroxydopamine (6-OHDA) injected bilaterally in the same region were tested for effects of adrenergic receptor blockers on a lever-pressing behavior to obtain the brain reward. The neonatally treated animals (16 microgram total dose, 8 microgram X 2) self-stimulated at abnormally high rates compared with controls. Yohimbine (5 mg/kg i.p.) and phentolamine (5 mg/kg) suppressed self stimulation in controls and treated subjects. Phenoxybenzamine (10 mg/kg) reduced the response rate for the brain reward but did not abolish the behavior in the 6 OHDA-treated animals and had minor effects in controls. Propranolol (10 mg/kg) had no effects. The 6-OHDA subjects tested for the effects of D-amphetamine and L amphetamine (0.5 mg/kg) showed facilitation of responding after the former but not after the latter. Self-stimulation in the 6-OHDA subjects was suppressed by treatment with alpha-methyl-p-tyrosine and pimozide. The significance of these findings is discussed in terms of the use of alpha-adrenoreceptor antagonists to separate the pre- from the post-synaptic action of released norepinephrine and in terms of the norepinephrine hypothesis of rewarding effects of brain stimulation in the dorsal pons. PMID- 6266597 TI - Amino acid transmitter receptor binding in synaptic membranes from normal and vitamin B12 deficient fruit bats. PMID- 6266598 TI - The dendritic response to GABA in CA1 of the hippocampal slice. AB - Application of GABA in the dendritic region of pyramidal cells elicits a depolarization which, in fact, is the sum of a hyperpolarizing and a depolarizing process. At the reversal potential of the depolarizing response (-42 mV) the GABA induced current fluctuations do not have a minimum. Consequently, a conductance change to more than one ion is involved. Cl- is in part responsible, Ca2+ is not because Mn2+ and Mg2+ do not change the response. Whether Na+ is involved is uncertain. Substitution with choline had no effect but choline may permeate through the membrane during the depolarizing response. Nipecotic acid inhibits a Na+-GABA uptake mechanism but does not change the dendritic response. PMID- 6266599 TI - Ultrastructure of GABA-neurons in cultures of rat neostriatum. AB - The subcellular distribution of glutamate decarboxylase (GAD) was revealed by electron microscopic immunocytochemistry in primary cultures of the rat neostriatum. Immunoreactivity was restricted to a small nerve cell type with rich amounts of free ribosomes and an indented nucleus. Glial cells were non-reactive. The results indicate that GABA-synthesizing neurons are viable in culture conditions and suggest that neostriatal GABA-neurons are small cells with simple ultrastructure since larger cells did not possess immunoreactivity. PMID- 6266600 TI - Localization of cholecystokinin receptors on neuronal elements in rat caudate nucleus. AB - Various chemical and physical lesions were employed to elucidate the cellular localization of cholecystokinin (CCK) receptors in the rat caudate nucleus. A wide knife cut severing all caudal afferents reduced caudate CCK receptors by approximately 25%, indicating that some receptors lie on axons and (or) terminals of neurons originating outside of the caudate. However, most CCK receptors appear to be located on neuronal cell bodies intrinsic to the caudate nucleus, since local injections of kainic acid reduced caudate CCK receptors by approximately 75%. These findings are similar to recent data from our laboratory on the concentration of CCK receptors in the basal ganglia of patients with Huntington's disease, and suggest that CCK may be involved in the regulation of extrapyramidal motor function. PMID- 6266601 TI - Morphine and ACTH1-24: correlative behavioral excitations following micro injections in rat periaqueductal gray. AB - Rats implanted with bilateral cannulas in the periaqueductal gray exhibited similar behavioral excitations following microinjections of morphine sulphate and ACTH1-24. Injections were more effective when the sites were located within rather than below the periaqueductal gray. Analgesia was observed following morphine but not ACTH microinjection. These results confirm that morphine exerts a dual action, inhibitory (i.e. analgesic) and excitatory, with ACTH mimicking only the latter action. PMID- 6266602 TI - Strain differences in pituitary beta-endorphin and ACTH content in inbred mice. AB - The whole pituitary contents of beta-endorphin and ACTH were found to vary widely among 5 inbred strains of mice. beta-endorphin values were 2.5-fold different and ACTH values 1.5-fold. Strains low in beta-endorphin were also low in ACTH. The existence of genetic differences raises the possibility that there exist, or can be developed, strains with extremely low or high levels of these peptides that would aid research directed at elucidating the physiology of opioid peptides. PMID- 6266603 TI - Development of the cat peripheral auditory system: input-output functions of cochlear potentials. AB - Compound auditory nerve action potentials (APs) and cochlear microphonics (CMs) were recorded from the round-window of kittens aged 3-9 weeks and of adult cats. Animals were anaesthetized and pure tone stimuli were delivered via calibrated, sealed, transducer systems. AP and CM amplitude and AP latency were measured over a wide range of stimulus intensities (up to 80 dB SPL) and at 5 octave-interval stimulus frequencies (1-16 kHZ). At low stimulus intensity levels, AP amplitude had attained adult levels to low and high frequency stimuli by 6 1/2 weeks of age and to mid-frequency stimuli by 9 weeks. As stimulus intensity levels were increased, the kitten input-output functions diverged progressively from those of the adults. At these higher intensity levels, AP amplitude maturation in even the 9 week animals was incomplete. AP latencies to stimuli of all frequencies shortened between the third and fourth weeks but remained stable thereafter. CM amplitude also reached maturity by the fourth week. These findings suggest that the development of AP after the fourth week consists of an increase in the synchrony of auditory nerve fibre responses, since both the fine structure of the cochlea and the responses of single nerve fibres are known to be mature by the end of the first postnatal month. PMID- 6266604 TI - Autoradiographic localization of specific kainic acid binding sites in pigeon and rat cerebellum. AB - The pigeons cerebellum contains a unique kainic acid binding site characterized by a relatively low binding affinity and cooperative binding properties. Dry mount autoradiographs of incubated tissue sections demonstrate that this type of binding site is exclusively localized in the molecular and Purkinje cell layers of the cerebellar cortex, suggesting that it is related to the Purkinje cell dendritic tree. The affinity, cooperativity and pharmacological properties of the binding were not modified by prior perfusion of the brain with a low concentration of formaldehyde. Moreover, the maximal binding was higher in tissue sections than in membrane preparations. The selective localization and specific kinetic properties of this binding site suggest that it may play a physiological role. The high affinity type of binding site, which is present in both rat and pigeon cerebellum, is localized in the molecular, and to a lesser extent, the granular layer. This may imply that this second binding site is related to other types of cellular elements, such as the granule cells. PMID- 6266605 TI - The role of opiates and endogenous opioid peptides in the regulation of rat TSH secretion. AB - The administration of morphine to rats at room temperature is reported to suppress serum thyrotropin (TSH) levels by a hypothalamic mechanism. However, it is unknown whether endogenous opioid peptides (EOP) are involved in the control of TSH secretion. The present studies show that naloxone (10 mg/kg, i.p.) an opiate-receptor antagonist, prevented the decline in rat serum TSH which occurs with heat exposure. Morphine sulfate (20 mg/kg, i.p.) treatment prevented the cold-induced elevation in serum TSH and pretreatment with haloperidol (0.3 mg/kg, i.p.) eliminated morphine's influence. Medial-basal hypothalamic thyrotropin releasing hormone (TRH) content, measured by RIA, increased in the morphine treated rats which were exposed to 4 degrees C. A submaximal intravenous dose of TRH (300 ng/100 g) was given to determine whether morphine suppresses serum TSH through the release of hypothalamic thyrotropic inhibitors. Morphine pretreatment did not alter TSH stimulation by TRH. Morphine alone or combined with TRH did not alter basal or stimulated TSH secretion in vitro. These studies strongly suggest that, in rats, the EOP modulate TSH secretion under conditions such as acute heat exposure which was associated with a decline in serum TSH. Under specific circumstances, the suppression of serum TSH by morphine may be dopamine dependent. PMID- 6266606 TI - Microiontophoretic study of the GABA receptor in the feline caudate nucleus. AB - The effect of microiontophoretic application of GABA and its antagonist, picrotoxin, on the firing of neurons in the feline caudate nucleus (CN) was studied. Firing was elicited by stimulation of the CN a few millimeters from the recording site. Increasing ejection currents of GABA produced a dose-dependent decrease and eventual blockade of the firing of CN neurons. The GABA current which reduced firing by 50% (ED50) was 7 nA. The Hill coefficient for the action of GABA was calculated as 1.8, indicating that a minimum of two independent subunits of the GABA receptor might need to be simultaneously occupied to activate the conductance change which produces the depressant effect. Picrotoxin blocked the action of GABA in a manner suggestive of a competitive antagonism. Dose ratios for the effects of GABA alone and of GABA during picrotoxin iontophoresis showed the dissociation constant (KD) of picrotoxin for the GABA receptor in the CN to be approximately 5 microM. Our results agree with those reported for different parts of the nervous system in various species, suggesting that the receptor which mediates the depressant effect of GABA in the CN has properties similar to striatal GABA receptors characterized in in vitro studies. PMID- 6266607 TI - Histamine-activated adenylate cyclase in brain homogenates of several species. AB - Histamine has been shown to activate cyclic AMP synthesis in brain slices and homogenates of certain species, although less is known about species differences in brain homogenates. Dutch Belted and New Zealand White rabbit brain homogenates contained a histamine-responsive adenylate cyclase similar to that of the guinea pig. In contrast, adenylate cyclase of gerbil and hamster brain exhibited little or no stimulation by histamine. Male rat hypothalamic homogenates contained adenylate cyclase, but also exhibited minimal stimulation by histamine, in disagreement with some recent reports. Detailed studies of the conditions of assay failed to resolve this discrepancy. PMID- 6266608 TI - Different opioid systems may participate in post-electro-convulsive shock (ECS) analgesia and catalepsy. AB - Administration of electroconvulsive shock (ECS) to rats results in post-ictal analgesia and catalepsy both of which can be partially reversed by the opiate antagonists, naloxone and naltrexone. Tolerance to both phenomena develops following daily ECS administration for 10 days. However, qualitatively different patterns of tolerance development of analgesia and catalepsy are seen. Naloxone treatment prior to ECS provides partial protection against the development of tolerance to ECS-induced catalepsy but does not present the tolerance to post-ECS analgesia. In contrast, the long-lasting opiate antagonist, naltrexone, blocked the development of tolerance to ECS analgesia. Furthermore, the same animals that showed tolerance to the analgesic effects of repeated ECS failed to show analgesia following the administration of 10 mg/kg of morphine while naltrexone, but not naloxone, treatment prior to ECS blocked the development of cross tolerance to morphine analgesia. A dose-response investigation of morphine's action (5, 10, 15 and 20 mg/kg) in additional animals receiving 10 daily administrations of ECS reveals that a greater tolerance to morphine's motor inhibitory effect than to its analgesic effect results from repeated ECS administration. Finally, animals receiving daily injections of either a low (10 mg/kg) or a high (100 mg/kg) dose of morphine for 10 days showed markedly attenuated post-ECS analgesia and catalepsy. However, whereas similar effects of opiate antagonists and the chronic administration of both doses of morphine were observed with post-ECS catalepsy, analgesia was least affected by naloxone (50% of control) and most affected by the chronic high dose of morphine (14% of control). Furthermore, a similar degree of tolerance to post-ECS analgesia was seen following either repeated ECS in drug-naive animals or the chronic administration of the high dose of morphine. Thus, the partial naloxone blockade of ECS analgesia and the more substantial attenuation of post-ECS analgesia seen in morphine-tolerant animals provide different estimates of opioid involvement in these phenomena. It is proposed that these results may demonstrate the involvement of different opioid systems in analgesia and catalepsy and it is suggested that more than one opioid system may also be involved in post-ECS analgesia. PMID- 6266609 TI - Electrophysiological abnormalities in chronic epileptogenic foci: an intracellular study. AB - Intracellular recordings were performed from chronic cobalt epileptogenic foci in rats. Two main features were found: (a) in 29% of the neurons, depolarizations of long duration occurred coinciding with cortical surface paroxysms; and (b) in 13% of the neurons, partial spikes, whose amplitude varied little with membrane DC potential changes, occurred. It is suggested that these phenomena have a dendritic origin, and possible mechanisms underlying the generation of paroxysmal events are discussed. PMID- 6266610 TI - Acute enhancement of spinal cord synaptosomal (Na+ + K+)-ATPase activity in cats following intravenous methylprednisolone. AB - The acute intravenous administration of high doses of methylprednisolone sodium succinate (15-90 mg/kg) to cats enhanced (Na+ + K+)-ATPase activity as much as 2 fold in synaptosomes prepared from lumbar spinal cord removed following drug administration. The effect was apparent within 5 min and was statistically significant at 1 h following a single injection of methylprednisolone 90 mg/kg. (Na+ + K+)-ATPase activity had returned to control levels by 24 h post-injection. The implication of these findings to the treatment of spinal cord trauma and the reported neurophysiological effects of glucocorticoids are discussed. PMID- 6266611 TI - Rat brain 5'-nucleotidase: developmental changes in myelin and activities in subcellular fractions and myelin subfractions. AB - The activities of 5'-nucleotidase, measured in brain homogenates and myelin isolated from rats at 21, 60 and greater than 90 days of age, were compared to values for two other myelin-associated enzymes, 2',3'-cyclic nucleotide 3' phosphohydrolase (CNP) and carbonic anhydrase. Whereas the activities of all 3 enzymes were higher in brain homogenates from 60-day-old rats than in those from 21-day-old rats, only 5'-nucleotidase increased significantly in specific activity in both homogenates and myelin after the age of 60 days. The ratios of 5'-nucleotidase to the myelin basic and proteolipid proteins in subcellular fractions from adult rat brain suggested that the microsomal fraction was the only fraction containing 5'-nucleotidase levels not attributable to contamination by myelin membranes. Like carbonic anhydrase, 5'-nucleotidase had a greater distribution than CNP into microsomes of adult rats. When purified myelin was fractionated on a density gradient, the specific activity of 5'-nucleotidase was highest in the heaviest subfraction, with recovery of significant activity occurring, however, in all 3 subfractions. In rats over 60 days of age the recovery of 5'-nucleotidase in myelin was almost as high as that of the relatively myelin-specific enzyme CNP, suggesting that myelin may be the predominant, although not exclusive locus of 5'-nucleotidase in the adult rat brain. PMID- 6266612 TI - Requirements for growth of neurites from embryonic chick cerebellum in culture. AB - Embryonic chick cerebella were cut into pieces and cultured under various conditions. Neurites were extended actively to collagen gel for a week or so and then degenerated. The neurite growth for the first two days was similar, also in the serum-free medium. Among 15 substances tested, insulin and cyclic AMP facilitated the growth. PMID- 6266613 TI - Opiate receptor ontogeny and morphine-induced effects: influence of chronic footshock stress in preweanling rats. AB - The ontogeny of opiate receptors was examined in various CNS regions of preweanling rats which received either daily inescapable footshock stress, exposure to a footshock apparatus without shock, or no handling from birth to 21 days of age. At 21 days of age, each of these treatment groups was also assessed for morphine-induced changes in activity, hot-plate paw-lick latency, and core body temperature. Marked regional differences in [3H]naloxone binding capacity were observed from 7 to 21 days of age in spinal cord, medulla-pons, midbrain, hypothalamus, striatum, and cortex. Caudal regions approached adult-like [3H]naloxone binding before rostral regions. The normal ontogeny of opiate receptors was not significantly influenced by the chronic footshock treatment. However, footshock treatment significantly reduced the efficacy of morphine (2 mg/kg) in producing hypoactive and antinociceptive effects, but not in producing a hyperthermic effect. These results demonstrate that stress-related changes in the behavioral efficacy of morphine do not necessarily depend upon changes in those opiate receptor populations that bind naloxone. PMID- 6266614 TI - Ouabain binding to chick embryo neuroretina during development in ovo and in monolayer cultures. AB - Eight-day-old embryo neuroretinas (NR) were dissociated and cultured as monolayer. [3H]Ouabain binding was investigated during the culture period. [3H]Ouabain binding to NR increases continuously until around the tenth day of culture, but after that it gradually decreased. On the other hand, [3H]ouabain binding to NR during in ovo development continued to increase until the embryo was 20 days old. Na-K-ATPase activity was also compared with [3H]ouabain binding during development in ovo and in monolayer culture. It was found that changes in Na-K-ATPase activity of NR in vitro and in ovo were different from those of [3H]ouabain binding activity. Exposure of NR at the second day of culture to 0.1 mM ouabain for 8 h resulted in the degeneration of some differentiated neurons (rosette-formed cells), but new rosettes were soon re-formed after the withdrawal of ouabain, and [3H]ouabain binding to the ouabain-treated NR was decreased by 30%. Ouabain-treatment of NR in 10-day-old cultures completely destroyed the aggregated neurons, but did not apparently injure the glial cell layer. [3H]Ouabain binding decreased more than 90% in the ouabain-treated NR. These results suggest that [3H]ouabain binding activity of NR and the sensitivity to ouabain toxicity are useful indicators for differentiation and development of neurons in the cultured retinal cells. PMID- 6266615 TI - Diazepam binding of dissociated hippocampal cultures from fetal mice. AB - Primary cultures of dissociated hippocampi from fetal mice examined for the presence of binding sites for [3H]diazepam. The binding assays were done with living cells still attached to the culture dish. The cells contain high affinity binding sites for [3H]diazepam, Kd = 5 nM, which are completely inhibited with 20 nM R05-4864 but only 26% with 20 nM lorazepam. The binding was inhibited by purinergic compounds and by quinidine. The living cell did not exhibit increased binding of [3H]diazepam in the presence of GABA and in fact a slight decrease in binding was found. This was also found when live, intact C6 glial cells were investigated. These observations suggest that the use of living cells to study the benzodiazepine receptor is valuable and maybe necessary to fully characterize this receptor. PMID- 6266616 TI - Differential effects of cyclic AMP and cholera toxin on nerve growth factor induced neurite outgrowth from adrenal medullary chromaffin and pheochromocytoma cells. AB - The extension of neurites from adrenal medullary chromaffin cells and PC 12 cells upon addition of nerve growth factor (NGF) has been proposed to be mediated by cyclic AMP. It is shown here that substances increasing intracellular cyclic AMP levels have a reverse effect on NGF-induced neurite outgrowth of these two related cell types. Hence, cyclic AMP is not generally involved in neurite outgrowth from NGF responsive cells. Furthermore, it is concluded that PC 12 cells cannot always be considered as a suitable model for adrenal medullary chromaffin cells. PMID- 6266617 TI - [Protein content in lung lavage specimens from rats of different provenience following administration of silica dust (author's transl)]. PMID- 6266618 TI - Interaction of selectively spin-labeled 70S ribosomes with tRNAPhe. An electron paramagnetic resonance study. AB - 70S ribosomes from Escherichia coli, selectively spin labeled on the SH groups of proteins S18, S12, S21, S17, and L27, were used to study the formation of the tertiary complex ribosome-poly(U)-tRNAPhe. Most of these ribosomal proteins are located in the region of binding of tRNA. The electron paramagnetic resonance observable structural change suggests a loosening of the ribosome structure upon binding of the tRNA molecule. PMID- 6266619 TI - Drinking water vaccination against infectious laryngotracheitis. AB - Chickens varying in age from ten days to five years were vaccinated with 10(1.3), 10(2.3) and 10(3.3) EID50 per bird of a commercial infectious laryngotracheitis drinking water vaccine. The vaccine gave no adverse reaction in the dose range tested. Five weeks after administration of 10(3.3) EID50 per bird 70% were protected against the intratracheal challenge with virulent infectious laryngotracheitis virus. Doses of 10(1.3) and 10(2.3) EID50 per bird did not give protection. No serological response could be detected by the neutralization test even in the group that had received 10(3.3) EID50 per bird. No contact spread of virus was detected from 14 days post-vaccination. Carriers of vaccine virus could not be demonstrated. PMID- 6266620 TI - Neonatal bovine enteritis: detection of rotavirus by counterimmunoelectrophoresis and enzyme-linked immunosorbent assay. AB - Counterimmunoelectrophoresis and enzyme-linked immunosorbent assay specific for rotavirus were performed on 253 calf gut and fecal specimens from eastern North Dakota. Rotavirus antigen was detected in 29 specimens by counterimmunoelectrophoresis and in 52 specimens by enzyme-linked immunosorbent assay. All of the counterimmunoelectrophoresis-positive specimens were positive by enzyme-linked immunosorbent assay. The counterimmunoelectrophoresis and the enzyme-linked immunosorbent assay, using a rabbit antirotavirus antibodies produced a golf ball-induced granuloma, were rapid and specific tests for the detection of rotavirus. PMID- 6266621 TI - Transformed phenotypes in long-term cultures persistently infected with bovine leukemia virus. AB - Two cell lines, 3178 and FLK, were established respectively from calf form bovine lymphosarcoma and from fetal lamb kidney cells inoculated in vitro with bovine leukemia virus. These two cell lines persistently infected with bovine leukemia virus were maintained for more than 150 passages over three years. They exhibited the characteristics of transformed cell lines in vitro: 1) anchorage independence, 2) increased saturation density and decreased population doubling time, 3) increased uptake of 2-deoxy-D-glucose and 4) tumorigenicity in athymic nude mice. PMID- 6266622 TI - Effects of extracts of toxic fescue given orally to rats. AB - Fresh fescue (Festuca arundinacea) was obtained from farms where toxicity was encountered in cattle grazing the fescue. The fescue was dried in a forced draft oven at 60 degrees C and then ground. The dry ground fescue was extracted with ether and then re-extracted with either 1% sodium bicarbonate (NaHCO3), sodium hydroxide or hydrochloric acid. The residual ether was evaporated and the residue resuspended in ethyl alcohol diluted with water 1% (control) and 1 mL of the above extracts of fescue were given daily to rats, via stomach tube, beginning the seventh day after breeding. Two of the seven rats given the 1% NaHCO3 fraction of the extract of fescue gave birth to live young. One of these litters contained only five pups, with one being stillborn. Three of the seven rats aborted, one gave birth to seven stillborn pups and one female died during birth. All females fed the 1% NaHCO3 and the other extracts of the fescue gave birth to normal litters. Rats fed the ether extract which was re-extracted with 1% NaHCO3, acidified and re-extracted with ether, dried and resuspended in 1% NaHCO3 produced similar reproductive problems as those rats given the ether extract of fescue which was re-extracted only once with 1% NaHCO3. Therefore, it appears that the toxic entity(s) of fescue can be extracted and that infertility/abortion/still-birth ratio of rats may be used as a bioassay. PMID- 6266623 TI - Inner structures of some coronaviruses. AB - When treated with formaldehyde, Tween 80, sodium oleate and Nonidet P-40, avian infectious bronchitis virus, porcine transmissible gastroenteritis virus, neonatal calf diarrhea coronavirus, porcine hemagglutinating encephalomyelitis virus as well as the human coronavirus show similar inner structures by negative staining. The first one is an inner membranous bag. This structure could be evaginated following treatments used and does not show the characteristic projections of coronaviruses. Subsequently, the inner fold could be separated from the outer membrane at the point of junction between these two membranes. Each virus does not react in the same way to the action of the different products. The transmissible gastroenteritis virus appears more sensitive to treatments than other viruses. On the other hand, the hemagglutinating encephalomyelitis virus is the most resistant. The variable sensitivities of these viruses are not related to the type of host-cells. Also, a second internal structure, which is more dense than the viral particle, encircles partially the aperture of the internal tongue-shaped structure and seems to emerge from the viral particle through the aperture of the inner bag. PMID- 6266624 TI - Murine polyoma virus transformation: integration and excision of the viral genome. PMID- 6266625 TI - Viral interference and persistence in Sindbis virus infected Aedes albopictus cells. PMID- 6266626 TI - Mechanisms of persistence in arenavirus infections: a brief review. AB - A characteristic of the arenaviruses is persistent infections in their natural host. Age at infection is an important factor in the establishment of persistence. Infections early in life regularly result in persistence and this appears to be related to the immaturity of the immune system. Persistently infected animals make antibodies to the viral antigens, which indicates that the animals are not tolerant with respect to B cell functions. However, cytotoxic T cells cannot be demonstrated in persistently infected animals, suggesting a defect in effector T cell functions. The mechanisms leading to this defect in cytotoxic T cells have not been resolved. Persistence of arenaviruses in cell cultures is also regularly observed but the molecular basis for survival of the virus and cell in long-term cultures has yet to be clarified. PMID- 6266627 TI - The genetic and physical basis of variability in Escherichia coli strains carrying a reference Inc N group plasmid. AB - The nature of basis of variability in the conjugational behaviour of RM98+ (RM98 carrying) strains of Escherichia coli K-12 that are otherwise similar in phenotype was studied. An explanation for such variability is provided. Some RM98+ strains of E. coli have a plasmid aggregate, which upon conjugation yields two different conjugative plasmids. The first (pCU1) is an N conjugative group plasmid by all available criteria. The second (pCU2) could not be placed in any conjugative group known among the Enterobacteriaceae. Reciprocal DNA hybridization experiments and the gel patterns displayed by the two plasmid DNAs upon digestion with different restriction endonucleases indicate no extensive sequence homology between pCU1 and pCU2. PCU2 DNA is much longer than pCU1 DNA. Despite the absence of extensive homology, the DNA of pCU1 and pCU2 can interact. Derivatives can be selected that have all the antibiotic markers of the aggregate plasmid but that neither contain nor segregate pCU2. It is shown that in such strains a DNA fragment of molecular weight 7.9 X 10(6) has been added to pCU1 concurrently with a tetracycline resistance marker originally present in pCU2 and absent in pCU1. These observations suggest that tetracycline resistance in pCU2 may be part of a large translocatable element. RM98 has been used to designate a reference Inc N group plasmid. The results presented indicate that this can lead to ambiguity. pCU1 would now be the appropriate reference plasmid. PMID- 6266628 TI - Disulfiram neuropathy. AB - Disulfiram (Antabuse) can produce neuropathy in daily doses of less than the usually recommended 500 mg. The four recent cases reported in this paper emphasize the need for greater recognition of this condition. Nerve biopsies showed axonal degeneration. The neuropathy is difficult to distinguish from that associated with ethanol abuse. Disulfiram neuropathy occurs after a variable latent period (mean 5 to 6 months) and progresses steadily. Slow improvement may occur when the drug's use is stopped; often there is complete recovery eventually. PMID- 6266629 TI - Carcinoma of the breast in men in Alberta. PMID- 6266630 TI - Bovine herpesvirus type 1 in the sperm of a bull from a herd with fertility problems. AB - A herd of 125 Holstein cows manifested fertility problems for two years. The number of services per pregnancy was 2.97, conception rate was 33% after the first service, and the average number of open days was 127. Abortions occurred in four cows over the last 12 months. The herd was not vaccinated against any disease. Natural service by a bull and artificial insemination were used for breeding the cows. Bovine herpesvirus type 1 was demonstrated in sperm heads from the bull by direct and indirect fluorescent antibody techniques, and the virus was isolated on cell cultures. The virus was also isolated from the uterine secretions of some cows and from two aborted fetuses. PMID- 6266631 TI - Isolation and growth characteristics of continuous cell lines from small-cell carcinoma of the lung. AB - Sixteen continuous tumor-cell cultures have been isolated from 91 tissue specimens from patients with small-cell carcinoma of the lung. Biopsy and autopsy specimens of primary and metastatic tumors have been utilized. The developing cell lines were recognized by proliferation of tumor cells in the culture from one to 14 weeks after explanation and have been maintained for up to four years. Primary lung tumor, bone marrow aspirations, pleural effusions and other metastases have all been productive explant material for the development of cell lines. Their human origin has been demonstrated by chromosome and/or isoenzyme analysis. Dense core vesicles, characteristically found in small-cell tumor cells were observed by electron microscopic examination of cultured cells. Growth rates in vitro have been measured and the in vitro cycle time in tumors of one cell line (DMS 79) has been compared with in vivo cycle time in tumors arising from DMS 79 cells in nude athymic mice. PMID- 6266632 TI - Enzyme-linked immunosorbent assay for herpes simplex virus tumor-associated antigen. AB - The antibodies against herpes simplex virus (HSV) tumor-associated antigen (TAA) in human sera were investigated by the enzyme-linked immunosorbent assay (ELISA). By combining the findings of antibody levels in many human sera, a significant level of discrimination between normal and cancer sera could be reached. Thus, 57 of 74 pathological sera had increased levels of antibodies against HSV-TAA antigen as compared to 26 of 512 normal sera. A significant correlation between the ELISA values and complement fixing (CF) and radioimmunoassay (RIA) values was also found. The results suggest that serodiagnosis with the ELISA test may therefore be of some use in the detection of specific antibodies against HSV-TAA antigen in sera of cancer patients. PMID- 6266634 TI - Glioblastoma multiforme following prophylactic cranial irradiation and intrathecal methotrexate in a child with acute lymphocytic leukemia. PMID- 6266633 TI - Complete response of a metastatic adenoid cystic carcinoma of the parotid gland to chemotherapy. PMID- 6266635 TI - The characteristics of long-term survivors of lung cancer treated with radiation. AB - Between 1968 and 1974, 348 patients with lung cancer were primarily treated with radiation therapy. There were 66 such patients (19%) who survived a minimum of 18 months and are the subject of this report. Of this group, 30 patients have no evidence of disease from 18-96 months, with a median follow-up of 38 months. Thirty-three patients are dead of disease. The five-year actuarial survival of the total group of 348 patients was 5.6%. There were 14 stage I and II patients who survived a minimum of 18 months, of whom 11 had no evidence of disease. Of the 42 Stage III patients, 18 presently show no evidence of disease. There were 13 patients who failed with locally recurrent disease; in this group a dose response relationship was demonstrated. A local failure rate of 50% (4/8) was observed for patients who received fewer than 5000 rad, 22% (6/27) for patients receiving 5000-5500 rad, 18% (2/11) in patients receiving 5500-5900 rad, and 5% (1/20) for patients who received more than 5900 rad. Radiotherapeutic technique was a significant variable in local failure. Forty-six percent (6/13) of those patient failures may have been eliminated with the use of careful treatment planning with simulation. A statistically significant difference in dose was noted for patients with central recurrence, mean dose 4725 rad, 1561 RET, 81 TDF, when compared with patients with control of gross disease with radiation, mean dose 5740, 1880 RET, 108 TDF. There were four patients with marked early complications (6%) and eight patients with late complications (12%). There were no deaths attributable to radiation. Although most patients with advanced lung carcinoma die of distant disease, a significant number of patients can achieve long-term survival when radically treated with high-dose radiation therapy. PMID- 6266636 TI - Nuclear bone imaging in metastatic cancer of the prostate. PMID- 6266637 TI - Pseudoneoplastic proliferation of endocrine cells in pancreatic fibrosis. PMID- 6266638 TI - Evaluation of 5'-nucleotidase as an enzyme marker in ovarian carcinoma. AB - A plasma membrane ectoenzyme in mammalian cells, 5'-nucleotidase, was evaluated as a marker for ovarian carcinoma. Activities of this enzyme were determined in homogenates from normal (N = 17) and malignant ovaries (N = 17), as well as in the sera from control women (N = 35), ovarian cancer patients with active disease (N = 24), and those in clinical remission (N = 9). A significant reduction of the activity of 5'-nucleotidase was observed in tumor homogenates compared with homogenates from normal ovaries. Levels of this enzyme in the sera of ovarian cancer patients were higher than in control women, suggesting the possibility of shedding of this enzyme from the tumor cell surface to the systemic circulation of the host. The diagnostic value of serum 5'-necleotidase levels was compared with another enzyme marker for ovarian carcinoma, viz. serum glycoprotein:galactosyltransferase. The upper limit of normal was set at 2 SD higher than the normal mean. Elevation of serum 5'-nucleotidase was observed in 12/24 (50%) patients with active disease, and 1/9 (11%) patients with clinical remission. In contrast, serum glycoprotein:galactosyltransferase was elevated in all the serum samples from patients with active disease and in none of those with clinical remission. There was some correlation between the serum levels of 5' nucleotidase and those of glycoprotein:galactosyltransferase (0.01 less than P less than 0.05). Elevation of 5'-nucleotidase in the serum of these patients was not due to liver metastasis. Serum 5'-nucleotidase levels seem to correlate with disease status in some ovarian carcinoma patients, but in general it is inferior to serum glycoprotein:galactosyltransferase as a tumor marker. PMID- 6266639 TI - Antibodies to mouse mammary tumor virus-related antigen in sera of patients with breast carcinoma. AB - Sera from patients with breast carcinoma, benign breast disease, malignancies other than breast carcinoma, and healthy female controls were analyzed by indirect immunofluorescence for the presence of antibodies directed toward antigens of mouse mammary tumor. Sera from 56 to 137 (40.9%) patients with breast carcinoma were positive. Positive reactivity was also found in sera from 5 to 27 (18.5%) patients with benign breast disease, in 7 of 60 (11.7%) patients with malignancies other than breast carcinoma, and in 2 of 56 (3.6%) female controls. In the group of patients with breast carcinoma a correlation was noted between age and the probability of detection of these antibodies. Histopathologic examination of breast cancers indicated that antibodies to antigens in mouse mammary tumors were more often found in patients with infiltrating ductal carcinoma of the mucinous type than with other types of breast tumors. No correlation was demonstrable between the incidence of detection of these antibodies and the stage of the disease. Immunochemical analyses indicated that the antibody activity was present in IgG and IgM classes of immunoglobulins. The human antibodies to antigens in mouse mammary tumors could be removed from patients' sera by absorption with disrupted mouse mammary tumor virus (MMTV) but not with gp52 or gp34 (52,000 and 34,000 dalton polypeptides) of MMTV, or with Rauscher mouse leukemia virus (MLV). PMID- 6266640 TI - Patterns of failure in patients with inoperable carcinoma of the lung. PMID- 6266641 TI - Clinical features of hepatocellular carcinoma: review of 211 patients in Hong Kong. AB - A retrospective study of 211 patients with proven hepatocellular carcinoma (HCC) was made. The commonest symptoms were anorexia and malaise (73%). Five patients (2.5%) had near-normal biochemical tests despite the presence of massive tumors. Diagnostic yield from angiography, percutaneous peritoneoscopic biopsy, or scintiscanning was 87-98%. Three percent of the patients had resectable tumors. Median survival for patients with untreated disease was 3.5 weeks. Apart from histology, the total serum bilirubin level was the only factor of prognostic value. Only 12 patients had preexisting symptomatic cirrhosis. When compared with 80 patients with symptomatic postnecrotic cirrhosis without malignancy, patients with HCC had higher SGOT:SGPT ratio, Higher serum albumin levels, and higher platelet counts. There was only minimal overlap of patients with symptomatic postnecrotic cirrhosis and those with HCC. The authors conclude that their patients with HCC appeared late for treatment. A probable difference in the development of symptomatic postnecrotic cirrhosis and of HCC with asymptomatic postnecrotic cirrhosis is suggested. PMID- 6266643 TI - Labeling and distribution of technetium-99m Corynebacterium parvum as determined by whole-body imaging. PMID- 6266642 TI - Combination chemotherapy with and without the methanol-extracted residue of bacillus Calmette-Guerin (MER) in extensive non-small-cell lung cancer: a prospective randomized study for the Piedmont Oncology Association. AB - One-hundred-three patients with extensive non-small-cell lung cancer were entered into a prospective, randomized trial to determine the value of MER as an adjuvant to chemotherapy. Patients were stratified according to histology and performance status. All patients received CCNU, methotrexate, and Adriamycin with 48 patients also receiving MER. All patients had a performance status of 2 or less (less than 50% bedridden), 49% had prior radiation therapy, only one patient had prior chemotherapy, and all had extensive disease. Of the patients, 42% had epidermoid cancer, 21% had large cell cancer, 32% had adenocarcinoma, and 4% had mixed adenosquamous or undifferentiated carcinoma. The response rates and response durations of the two treatment regimens were similar. Of the patients, 18% had an objective response; in 4% it was complete. An additional 29% had a stable response. Median duration of response ranged from 21 to 23 weeks. Median survival rates for non-MER and MER treatment groups were 21.5 and 18.6 weeks, respectively. The four complete responders have a survival of 24, 85, 86+, and 129 weeks. MER did not improve response for hematopoietic tolerance, was associated with significant morbidity, and was poorly tolerated. The value of immunotherapy in lung cancer remains to be established. PMID- 6266644 TI - Risk of subsequent contralateral breast carcinoma in a population of patients with in-situ breast carcinoma. AB - One hundred ninety-one cases of unilateral noninvasive breast carcinoma were studied with regard to the development of subsequent cancers in the contralateral breast. The majority of patients were treated by mastectomy and have been followed for an average of nine years. Their overall survival did not differ significantly from that of age-specific population survival figures for U. S. women. Among all cases, 13 or 6.8% subsequently developed contralateral carcinoma; 3.1% of these contralateral tumors were invasive. The authors found only one histological type, namely lobular carcinoma in-situ for which the development of subsequent contralateral carcinomas was statistically significant. Seven of the 68 women with this type developed second breast cancers (10.3%; 4.4% of these were invasive). These data suggest that the occurrence of clinically apparent subsequent cancers developing in the opposite breast following the diagnosis of in-situ carcinoma is relatively small. PMID- 6266645 TI - Neuraminidase activity and cell surface sialic acid turnover in Rous sarcoma virus transformed chick embryo fibroblasts. AB - Neuraminidase activity of Rous sarcoma virus transformed chick embryo fibroblasts (RSV-CEF) was assayed using an exogenous substrate, neuraminlactitol-[3H], and endogenous, cell surface [14C]-N]-acetyl-neuraminic acid. RSV-CEF had higher neuraminidase activity toward both substrates than did chick embryo fibroblasts (CEF) or nontransformed, Rous associated virus infected CEF (RAV-CEF). The total sialic acid content of RSV-CEF was lower than CEF or RAV-CEF, and more of the total sialic acid was accessible to extracellular Clostridium perfringens neuraminidase. Activity of the enzymes synthesizing and degrading the substrate for sialyltransferase, cytidine-5'-monophosphate-N-acetyl-neuraminic acid (CMP AcNeu) was measured in order to determine whether control of substrate levels for sialyltransferase might contribute to the decreased levels of glycoprotein bound sialic acid. No change in activity of these enzymes was found in RSV-CEF as compared to CEF or RAV-CEF. PMID- 6266646 TI - Transformed cells exhibit altered response to db cycle amp-mediated modulation of protein phosphorylation and different endogenous phosphoprotein acceptors. AB - Endogenous protein phosphorylation has been studied in extracts from rat cells transformed by temperature-sensitive derivatives of Rous sarcoma virus which can reversibly express a transformed behavior at 33 degrees C and reacquire "normal" properties at 39 degrees C. The expression of transformation appeared associated with marked alterations in the type of phosphoprotein acceptors and with an increased protein kinase activity, particularly in detergent solubilized fractions. A comparison of the effect of dibutyryl cyclic AMP on protein phosphorylation revealed a transformation-dependent response, as well as a different effect of the cycle nucleotide in cytoplasmic and detergent solubilized fractions. Our studies suggest that the processes leading to malignant transformation are accompanied by altered response of the phosphorylating system to cyclic nucleotide-mediated modulation and by marked alteration in phosphoprotein acceptors. PMID- 6266647 TI - Correlation between the association and the desmutagenicity of benzo(a)pyrene by hemin: comparison with hemoproteins, transient metals and amines. AB - The mutagenicity of the potent carcinogen benzo(a)pyrene proved to be lost by binding with hemin and other tested compounds. The association constant (Kass) and the desmutation constant (Kmut) of benzo(a)pyrene and hemin were 8.5 x 10(4) M(-1) and 7.0 x 10(-4) M(-1), respectively. The correlation coefficient (gamma) of the association and the desmutation of benzo(a)pyrene and hemin was nearly 1, and the coefficient of regression of association on the desmutation, gamma (sigma ass/sigma mut), was 0.78. The correlation of other compounds, ferric chloride among transient metals, and 3,3'-diaminodipropylamine and p-phenylenediamine, were also almost 1 in both values, but their Kass an Kmut were must smaller than those of hemin: Kass:Kmut, 525 M(-1):520 M(-1) for ferric chloride, 2.2 x 10(3) M(-1):2.3 x 10(3) M(-1) for diaminodipropylamine and 175 M(-1):125 M(-1) for p phenylenediamine. Good agreement of Kass and Kmut means that the desmutation of benzo(a)pyrene is caused by binding with tested materials. PMID- 6266648 TI - Electron spin resonance of growing normal and virus-transformed cells. AB - A g = 2.003 ESR signal, attributed to a free radical localized in HeLa cell nuclei and mitochondria but absent in membranes and cytoplasm, has been studied as a function of the culture growth cycle in normal (NRK and 3T3) and virus transformed (NRK/RSV and 3T3/SV40) cells. For both these cell pairs, the signal is higher during the "lag" stage and lower during the "growth" stage. The average specific intensity of the signal in normal cells is about twice that in virus transformed cells. However, the maximal point of resonance during the lag state is higher in transformed cells than in normal ones. The lag stage in NRK and NRK/RSV cells is much longer than in 3T3 and 3T3/SV40 cells, while the maximal value of the g = 2.003 ESR signal occurs, early in the lag stage of 3T3 and 3T3/SV40 cells and late in the lag stage of NRK and NRK/RSV cells. PMID- 6266649 TI - Chromosomes and causation of human cancer and leukemia. XLV. Chromosome patterns in stimulated lymphocytes of chronic lymphocytic leukemia. AB - In the present study the B-cell mitogens from Epstein-Barr virus (EBV) and lipopolysaccharide-B from E. coli (LPS) were used to stimulate the blood cells of 27 patients with chronic lymphocytic leukemia (CLL) to undergo mitosis. In 14 CLL cases EBV was used as the only mitotic stimulant and in 5 cases both EBV and LPS. In 8 cases neither EBV nor LPS caused mitotic cells to appear. In 9 cases the cells were characterized by abnormal clones, including 5 cases with +12 (including 1 case with a possible Philadelphia chromosome), 2 cases with 14q+ and 1 case with an i(17q). No correlation was found between the types of surface membrane immunoglobulins and the chromosome abnormalities in the leukemic lymphocytes. The effects of EBV on normal lymphocytes were also investigated and found to be nonspecific (e.g., tetraploidy), although in every case EBV caused a definite increase in the mitotic index. The results indicate that 1) EBV and LPS stimulate leukemic cells of CLL to undergo mitosis, 2) about 50% of the patients have clonal abnormalities in the leukemic cells, and 3) CLL is associated with karyotypic changes seen in lymphoma (14q+), although the most common anomaly in our material was a +12. PMID- 6266650 TI - The mechanisms of endoreduplication. AB - Chinese hamster cells, Don line, were treated with concanavalin A (ConA), calcium ionophore A23187 (A23187), colchicine, sodium fluoride (NaF), 6-thiopurine, dibutyryl cyclic AMP (db-cAMP), and other nucleotides, alone or in combination. A23187 itself did not induce endoreduplication but did so in combination with ConA. NaF could induce endoreduplication and the combination of NaF and ConA showed a synergistic effect. db-cAMP suppressed the inducing activity of ConA. The findings that various chemicals are inducers of endoreduplication and that synergistic effects appear on combined treatments suggest that various mechanisms of induction of endoreduplication may exist. The chemical nature of the inducers and the suppressor, db-cAMP, implies that blocking of the phosphorylation of some cellular components may be involved as a main mechanism. Analysis of the endoreduplication cell cycle indicated that cells treated with reagents in S require a longer cell cycle than those treated in G2 and that the length of the lag period between induction treatment and the initiation of S, the length of S, and the length of G2 war variable. The inducers, induction mechanisms, and the cell cycle of endoreduplication seem to vary; however, the essence of endoreduplication is the omission of mitotic events by connecting S and G1. PMID- 6266651 TI - Combined effect of the extracts from Croton tiglium, Euphorbia lathyris or Euphorbia tirucalli and n-butyrate on Epstein-Barr virus expression in human lymphoblastoid P3HR-1 and Raji cells. AB - The combined usage of n-butyrate and 12-O-tetradecanoylphorbol-13-acetate (TPA) or the oily extracts from Croton tiglium, Euphorbia lathyris or Euphorbia tirucalli exerted a marked effect on induction of Epstein-Barr virus (EBV) associated early (EA) and viral capsid (VCA) antigens in EBV genome-carrying human lymphoblastoid cell lines. In producer P3HR-1 cells, the enhancing effect of the 2 components was additive both for EA and VCA, while in non-producer Raji cells, a synergistic increase of EA was observed. The possible implication of these findings relating to the cause of EBV-associated diseases is discussed. PMID- 6266652 TI - Mammary tumorigenicities of three chemically induced mouse kidney cell lines in syngeneic female hosts. AB - Three chemically induced, mammary tumour virus (MMTV) and leukemia virus (MuLV) producing, baby mouse kidney (BMK) cell lines derived from respectively strains BALB/c (-/HeA and -/CrglA) and C57BL/LiA were investigated for their mammary tumour (MT) evoking potentials in syngeneic female hosts. An i.p. inoculated virus-enriched fraction from A3 cells (BALB/c/HeA) had a similar oncogenic effect as i.p. and s.c. inoculated whole A3 cells. The average MT ages were reduced in all 3 groups. Cell lines BBM (BALB/c/CrglA) and BB (C57BL/LiA) were tested as i.p. inoculated whole cells. Again, the average MT age was reduced in thus treated BALB/c/Crgl females. In the case of C57BL/LiA the percentage of animals with MT was strongly increased in the BB cell inoculated group (1 MT in control group). Bioassay results corrected for intercurrent death cases (including leukosis) were statistically significant. It is concluded that the endogenous MMTV variants of the 3 mouse (sub-)strains are virulent MT evoking viruses in autologous hosts when they are induced. PMID- 6266653 TI - Inhibition of spontaneous hepatocarcinogenesis in C3H/HeN mice by transplanted hepatocellular carcinomas. AB - Cell suspensions of tumor fragments derived from spontaneous or chemically induced primary hepatocellular carcinomas obtained from inbred C3H/HeN mice were transplanted into young male mice of the same strain. Transplantable hepatocellular carcinomas were excised as soon as they were detected, and all recipient mice were killed at one year of age. In control C3H/HeN mice, the incidence of primary hepatocellular carcinomas was 41% (41 of 100). In mice in which there was no growth of transplantable carcinomas, whether originally given injections of tumor cell suspensions or fragments, the overall incidence of primary hepatocellular carcinomas was 49% (35 of 72) with one to six tumors per liver at time of sacrifice. Transplantable hepatocellular carcinomas were established only in mice that had received tumor fragments. In these mice, from which established transplantable hepatocellular carcinomas had been excised, the overall incidence of primary hepatocellular carcinomas was 12% (3 of 25) with one tumor being found in each of three livers. The time of appearance of excision of transplantable hepatocellular carcinoma did not affect this decrease in primary hepatocellular carcinoma incidence. PMID- 6266654 TI - Growth state-dependent alterations in the ability of 12-O-tetradecanoylphorbol-13 acetate to increase ornithine decarboxylase activity in Reuber h35 Hepatoma cells. PMID- 6266655 TI - Relationship between benzo(a)pyrene-induced DNA base modification and frequency of reverse mutations in mutant strains of Salmonella typhimurium. AB - Salmonella typhimurium cells (TA98 and TA100) were incubated with [3H]benzo(a)pyrene ([3H]BP) and induced rat liver microsomes. The BP-induced cytotoxicity and His+ reverse-mutation frequencies were determined, and bacterial DNA hydrolysates were chromatographed on Sephadex LH-20. Analysis indicated three principal DNA adducts formed from two diastereoisomeric BP diol-epoxides and a 9 hydroxy-benzo(a)pyrene metabolite. An 8.6-fold increase in TA100 cell concentration in the microsome incubation was paralleled by a 7.2-fold decrease in total adducts per cell and a 7.4-fold decrease in mutation frequency. Separate TA98 incubations were titrated with increasing concentrations of [3H](+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene ([3H]anti BP diol-epoxide), [3H](+/-)-7 beta, 8 alpha-dihydroxy-9 beta, 10 beta epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene [3H]syn BP diol-epoxide), or [3H]9 hydroxybenzo(a)pyrene. Linear, nonsaturated increases in DNA adduct levels were seen up to the highest observed concentrations of 4.00 microM BP diol-epoxide or 6.00 microM 9-hydroxybenzo(a)pyrene in both TA98 and TA100 cells. The increasing adduct levels were accompanied by linearly increasing mutation frequencies. At equivalent concentrations of the two DP diol-epoxides, an average of 8.2-fold more base substitution mutations (TA100) were seen than frameshift mutations (TA98). The results also indicate significant differences in absolute mutagenic efficiency (mutation frequency/unit modified DNA) between these three covalent DNA ligands (TA98, syn BP diolepoxide greater than 9-hydroxy-4,5-epoxy benzo(a)pyrene greater than anti BP diol-epoxide; TA100, 9-hydroxy-4,5-epoxy benzo(a)pyrene greater than syn BP diol-epoxide greater than anti BP diol epoxide). PMID- 6266656 TI - Inhibition in vivo of the formation of adducts between metabolites of benzo(a)pyrene and DNA by aryl hydrocarbon hydroxylase inducers. AB - The lungs of A/HeJ mice are susceptible to benzo(a)pyrene (BP)-induced neoplasia whereas the livers are resistant. Following p.o. administration of a carcinogenic dose of [3H]BP, radioactivity was associated with the DNA of both lung and liver. Analysis of the deoxyribonucleosides by high-pressure liquid chromatography showed that the major adduct in both tissues chromatographed as the (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BPDEI)-deoxyguanosine adduct. The (+/-)-7 beta, 8 alpha-dihydroxy-9 beta, 10 beta-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BPDEII)-deoxyguanosine adduct was 9 to 15% of the BPDEI adduct in both lung and liver. Although total DNA-associated radioactivity was approximately 12-fold higher in liver than in lung, the specific activities of the BP diol-epoxide adducts were approximately the same in these organs. Treatment of animals with beta-naphthoflavone (beta NF), an inhibitor of pulmonary adenoma formation, markedly decreased the amount of the BDPEI and BPDEII adducts in the lung and the liver. The decrease in the amount of these adducts in the lung correlates with the inhibition of tumorigenesis by beta NF. The inhibition of total DNA-associated radioactivity was significantly less than the BP diol-epoxide adducts. Thus, beta NF appears to inhibit BP-induced pulmonary neoplasia by reducing the amount of the BPDEI-deoxyguanosine adduct. Other inducers of aryl hydrocarbon hydroxylase were also tested for their effect on the formation of BP-deoxyribonucleoside adducts. Both 2,3,7,8 tetrachlorodibenzo-p-dioxin and Aroclor 1254 significantly reduced the amount of the BPDEI adduct in both lung and liver. These data would suggest that both 2,3,7,8-tetrachlorodibenzo-p-dioxin and Aroclor 1254, like beta NF, should protect against BP-induced pulmonary neoplasia. The effects of aryl hydrocarbon hydroxylase inducers on the binding of BP to DNA in vivo markedly contrast with their effect in vitro. Treatment of animals with aryl hydrocarbon hydroxylase inducers stimulates the formation of BP diol-epoxide adducts in vitro. The reason for the differences between our in vivo results and those predicted from in vitro studies is unclear. PMID- 6266657 TI - Aminoacyl fucosides as possible biochemical markers at tumorigenic and metastatic potential in herpes simplex virus type 2-transformed rat cells. AB - Two classes of aminoacyl fucosides termed FL3 and FL4 were studied as possible markers of tumorigenic and metastatic potential in herpes simplex virus type 2 transformed rat cells. In the present study, clonal cell lines of transformed highly tumorigenic and metastatic (t-REF-G-1.1), weakly tumorigenic and nonmetastatic (t-REF-G-2.1), nontumorigenic (t-REF-G-2.0), and secondary nontransformed rat embryo fibroblast cells were labeled with [3H]fucose, and cell extracts were analyzed for ratio of radioactivity incorporated into FL3 and FL4. Results indicated that, in extracts from t-REF-G-2.0 and nontransformed rat embryo fibroblast cells, the ratios of FL4/FL3 were 5.78 and 5.71, respectively. In contrast, t-REF-G-2.1 cells exhibited a FL4/FL3 ratio of 1.45, while t-REF-G 1.1 cells exhibited a FL4/FL3 ratio of 0.74. In subclonal cell lines isolated from TPA-treated and mock-treated t-REF-G-2.1 cells, the FL4/FL3 ratios correlated with the tumorigenic and metastatic potential of these subclones in newborn syngeneic White Buffalo rats. These data suggested that alterations in fucose-labeled components can be used to predict the tumorigenic and metastatic potential of herpes simplex virus type 2-transformed rat cells. PMID- 6266658 TI - Effects of murine leukemia virus infection on long-term hematopoiesis in vitro emphasized by increased survival of bone marrow cultures derived from BALB/Mo mice. AB - The effect of infection with Moloney murine leukemia virus (Mo-MuLV) on long-term bone marrow cultures was studied. Cultures were derived from the bone marrow of BALB/Mo mice, which carry Mo-MuLV as an endogenous virus, or from BALB/c, 129/J, or balb/c X 129/J mice that were infected with Mo-MuLV in vitro. The following parameters were tested: longevity of generation of granulocytes; biological properties of nonadherent cells in colony-forming assays for pluripotential stem cells and committed granulocyte-macrophage colony-forming unit culture, erythroid, or metachromasia-positive mast cell-basophil colony-forming cells; differentiation of nonadherent cells following cocultivation with thymic or bone marrow stromal cells; and generation of WEHI-3 dialyzed conditioned medium dependent permanent cell lines. Granulocytes were generated for 65 weeks in BALB/Mo marrow cultures, 31 weeks for BALB/c, 22 weeks in 129/J, and 28 weeks in balb/c X 129/J cultures. Exogenous infection of BALB/c cultures with Mo-MuLV increased the longevity of hematopoiesis to 41 weeks. Granulocyte-macrophage colony-forming unit cultures were produced for 61 weeks in BALB/Mo cultures, 25 to 40 weeks in Mo-MuLV-infected cultures, and 19 to 33 weeks in uninfected control cultures. Nonadherent cells harvested from BALB/Mo marrow cultures generated cloned permanent WEHI-3 dialyzed conditioned medium-dependent, nonleukemogenic granulocyte-macrophage colony-forming unit culture cell lines at greater efficiency than did Mo-MuLV-infected or uninfected BALB/c cultures. The cell lines differentiated to mature granulocytes following cocultivation with purified marrow or thymic stromal cells. There was no detectable differentiation of nonadherent cells to lymphocytes or mast cells. Thus, Mo-MuLV does not detectably transform granulocyte progenitor cells in vitro to granulocytic leukemia. However, Mo-MuLV replication stimulates self-renewal of granulocyte progenitor cells in both primary marrow culture and in suspension culture in WEHI 3 dialyzed conditioned medium. PMID- 6266659 TI - Epidemiological correlations between diet and cancer frequency. AB - The literature concerning international correlations between dietary items and cancer frequency is reviewed. An updated correlation of the most recent data on cancer mortality and food consumption is made. Strong and consistent correlations are reported between death rates of cancers of the colon and breast and the per capita consumption of total fat and of nutrients derived from animal sources, especially beef, pork, eggs, and milk. Similar but less consistent correlations have been reported with cancers of the prostate, ovary, and endometrium. In addition, correlations between precursor lesions of coronary heart disease and colon cancer in New Orleans autopsy populations are reported. Some studies suggest that milk intake correlates better with atherosclerotic disease while beef intake correlates better with colon cancer. Negative correlations of colon cancer rates and vegetable consumption are reported. Colon cancer rates also show negative correlations with stool weight, irrespective of the type of vegetable responsible for the increased bulk. Epidemiological data are consistent with the hypothesis that excessive beef and low vegetable consumption are causally related to colon cancer. These food items probably do not have a direct carcinogenic role but rather provide a microenvironment favorable to the actions of carcinogens. PMID- 6266660 TI - Dietary fat and its relationship to large bowel cancer. AB - Epidemiological data have provided clues to the etiological factors involved in large bowel cancer development. High intake of dietary fat tends to promote colon carcinogenesis. Studies in metabolic epidemiology have shown that the high dietary fat affects the metabolic activity of gut bacteria as well as the levels of secondary bile acids that may act as tumor promoters for the colon. Animal model studies indicate that total dietary fat, rather than type of fat, exerts a promoting role in colon carcinogenesis. PMID- 6266661 TI - The need for comprehensive diet studies to assess the relation of lipids to cancer. AB - Dietary lipids have been linked by both basic research and epidemiological evidence to the etiology of some cancers. It is yet unclear which lipid(s) may be active in the carcinogenic process, but one promising hypothesis concerns the interaction of cholesterol metabolites, considered a risk factor for colon cancer, and dietary fiber which may have a protective role. A multidisciplinary case control study currently underway is investigating the relationship and possible mode of action of fiber and bile acids on colon cancer. The study has epidemiological, biochemical, and pharmacological components that have been designed to integrate data on the intake and fate of lipids, dietary fiber, and other nutritional parameters in colon cancer cases and matched controls and in animal models. Subcomponents of the study deal specifically with the characterization of dietary fiber constituents and their in vivo effect on lipid metabolism. PMID- 6266662 TI - Effects of dietary essential fatty acids on murine mammary gland development. AB - Removal of unsaturated fatty acids from the diet of female C3H mice resulted in the gradual onset of essential fatty acid deficiency. Upon reaching the deficient state, alveolar components of the mammary gland began to regress as did the ovarian corpora lutea. An increase in the viscosity of microsomal membranes and a decrease in the number of prolactin binding sites also occurred concomitantly as the deficient state increased in severity. Modification of fats with the diet changes the fluidity of cellular membranes. This appears to alter the functionality of the membrane-associated receptors and their subsequent ability to respond to circulating hormones. PMID- 6266663 TI - Ultrastructural modifications of intestinal and colonic mucosa induced by free or bound bile acids. AB - There is substantial evidence that bile acids may enhance the colon tumorigenesis induced by chemical carcinogens and that agents stimulating increased bile acid excretion may show similar promoting or enhancing activity. To test the premise that these agents might modify topographical ultrastructure of the small intestine and colon in the absence of carcinogens, rats were fed for 6 weeks on chemically defined diets containing 2% levels of three commercial bile acid sequestrants or 15% levels of wheat brain, cellulose, pectin, or alfalfa. Major qualitative and quantitative deviations from normal morphology were observed with each of the three sequestrants. Similar but less dramatic modifications occurred with diets containing alfalfa or pectin, both of which either "bind" bile acids in vitro or result in increased bile acid excretion. Bran and cellulose which neither "bind" bile acids nor increase their fecal excretion, were without significant effects on intestinal or colonic morphology. The morphological deviations observed with bile acid sequestrants were shown to be a direct response to free or bound bile acids by comparing the morphological modifications resulting from daily intracolonic infusions of free bile acids, sequestrant-bound bile acids, or the sequestrant alone. PMID- 6266664 TI - Diet and excretion of bile acids. AB - In recent years, salient advances have taken place in the knowledge of the interaction of diets containing high-fat and certain type of fibers and the production of bile acids potentially relevant in the etiology of colon cancer. Other studies also indicate that a high intake of certain dietary fibers, in spite of high dietary fat, not only leads to an increase in stool bulk, thus diluting carcinogens and promoters in the gut, but also modifies the metabolism of these putative substances. These studies thus suggest that both high intake of total fat and low intake of certain fibers may be necessary for the full expression of risk to colon cancer. PMID- 6266665 TI - Animal studies implicating fat and fecal steroids in intestinal cancer. AB - There is epidemiological and experimental evidenced that the ingestion of excessive amounts of fat enhances intestinal cancer formation. This may be due to the interaction of luminal steroids with the bacterial flora in the colon, forming carcinogens or promoting agents. Increased fecal steroids induced by drugs, diet, or by mechanical means enhance intestinal tumor formation in rats given injections of azoxymethane. The effect appears to be promotional rather than initiative. Dietary fiber inhibits carcinogenesis only when the fat content of the diet is not excessive. Apparently, a quantitative relationship exists between these two dietary elements that further studies may define for prevention of cancer in humans. PMID- 6266667 TI - Working Group III: lipid metabolites and intestinal flora. Summary, conclusion, and recommendations. PMID- 6266666 TI - Effects of diet on the fecal excretion and bacterial modification of acidic and neutral steroids, and implications for colon carcinogenesis. AB - Diet-induced changes in the excretion and fecal concentration of bile acids have been associated with enhancement or reduction of chemically initiated colon carcinogenesis in experimental animals. Dietary lipid increases the excretion and fecal concentration of bile acids. Certain types of dietary fiber such as pectin and lignin also increase fecal sterol output. However, the predominant effect of food-derived fiber (e.g., wheat brain) is to increase stool bulk and, hence, reduce the concentration of fecal sterols. Although it has been suggested that the tumor-promoting activity of bile acids is enhanced following bacterial dehydroxylation, dietary factors appear to have limited effect on bacterial flora or acidic sterol degradation in the colon. PMID- 6266668 TI - Inhibition by membrane-bound low-density lipoproteins of the primary inductive events of mitogen-stimulated lymphocyte activation. AB - Low-density lipoproteins (LDL) inhibit phytohemagglutinin (PHA)-enhanced accumulation of calcium ion and cyclic guanosine 3':5'-monophosphate, and phosphatidylinositol turnover in human lymphocytes. Inhibition by LDL of PHA induced 32P incorporation into monophosphoinositide and cyclic guanosine 3':5' monophosphate accumulation correlates directly with inhibition by LDL of calcium ion accumulation. These results suggest that calcium ion accumulation is required for PHA to direct turnover of monophosphoinositide and cyclic guanosine 3':5' monophosphate synthesis in lymphocytes and that inhibition of this mitogen induced response by LDL may be a direct consequence of the ability of these lipoproteins to prevent calcium ion accumulation by the activated cells. The ability of LDL to suppress PHA-enhanced calcium ion accumulation is directly proportional to the amount of LDL localized at the cell surface, indicating that internalization of the lipoproteins is not required for immunoregulation. This conclusion is supported by two additional lines of evidence: (a) LDL depleted of the bioregulatory constituent cholesterol are as effective as are native LDL in suppressing lymphocyte response to PHA; and (b) LDL-Sepharose complexes which cannot be endocytosed by the cells are as immunosuppressive as soluble LDL. The data clearly establish that membrane-bound LDL may have a regulatory role. PMID- 6266669 TI - Effect of chronic potassium depletion on digitalis-induced inotropy and arrhythmias. AB - The arrhythmogenic and inotropic effects of digoxin were studied in normokalemic controls, chronically hypokalaemic, and potassium-repleted dogs instrumented to maintain heart rate, mean aortic pressure, mean left atrial pressure and autonomic tone constant. The duration of digoxin infusion needed to produce ventricular tachycardia (VT) was 56.7 +/- 3.6 min in depleted dogs, 69.0 +/- 2.7 min in controls (P less than 0.005 compared with depleted dogs), and 60.5 +/- 3.0 min in repleted dogs. Baseline left ventricular dP/dt (LV dP/dt) was similar in all groups. After digoxin, LV dP/dt increased more in controls and repleted dogs than in chronically hypokalaemic dogs; eg, after 45 min of digoxin infusion LV dP/dt increased 12.7 +/- 4.4% in hypokalaemic dogs; eg, after 45 min of digoxin infusion LV dP/dt increased 12.7 +/- 4.4% in hypokalaemic dogs, 43.8 +/- 3.3% in controls (P less than 0.025) and 39.3 +/- 8.5% in repleted dogs (P less than 0.025). The inotropic response to isoprenaline was also attenuated in the chronically hypokalaemic dogs. Plasma digoxin was similar in all groups. LV digoxin was also similar in control and depleted dogs. Although inhibition of Na+, K+-ATPase and the initial velocity of 3[H]-ouabain specific binding was less in depleted dogs at VT than in controls (P less than 0.05), the magnitude of this difference was not sufficient to explain the attenuated inotropic response. No histological abnormalities were seen on light or electron microscopy in any of the groups. Therefore chronic hypokalaemia has two deleterous effects. It increases sensitivity to the arrhythmogenic effects of digoxin and impairs the inotropic response to digoxin, and isoprenaline. PMID- 6266670 TI - [Endorphins -- new regulating peptides (author's transl)]. PMID- 6266671 TI - [Acute toxicity and radioprotective effectiveness of WR-2721 (Gammaphos) in rats (author's transl)]. PMID- 6266672 TI - [X-ray diagnosis and the treatment of synovial sarcoma (author's transl)]. PMID- 6266673 TI - Microfilaments interacting with heavy meromyosin and deoxyribonuclease I in cells of the ovarian follicle of a lizard. AB - Two types of filaments (microfilaments 4--6 nm in diameter, and intermediate filaments 7--10 nm in diameter) are common in the surface epithelial cells and theca fibroblasts of vitellogenic ovarian follicles of the lizard Anolis carolinensis. Heavy meromyosin (HMM), which forms complexes with actin filaments, interacts only with the microfilaments of theca fibroblasts. After myosin extraction of follicles no filaments disappeared, but when this treatment was followed by incubation with deoxyribonuclease I (DNA-ase I), which depolymerizes F-actin to G-actin, microfilaments disappeared from the theca fibroblasts. It is concluded that microfilaments in theca fibroblasts are actin-like and may contract to provide the mechanism of expulsion for the oocyte during ovulation. The intermediate filaments of the surface epithelial cells and theca fibroblasts may serve as a skeletal system for the large (up to 8 mm in diameter) vitellogenic follicle. PMID- 6266674 TI - Ultrastructural and cytochemical effects of trypan blue on TSH stimulation of thyroid follicular cells. AB - Ultrastructural and cytochemical techniques were used to study the effects of trypan blue on the response of mouse-thyroid cells to exogenous stimulation by thyroid stimulating hormone (TSH). The dye delayed the response to TSH resulting in decreased colloid-droplet formation in the apical region of the cells. The dye did not stop the shift of trimetaphosphatase activity from lysosomes to phagolysosomes. The duration of the TSH-induced response was shorter in the dye treated thyroids. Small vesicles, with trimetaphosphatase reaction product, were found near Golgi elements, phagolysosomes, and the plasma membrane facing rhe intercellular space of adjacent follicle cells. Their enzyme activity was not affected by exposure to the dye. These data indicate that the primary effect of trypan blue on the response of thyroid follicle cells to TSH stimulation was reduced endocytosis in the apical region resulting in fewer colloid droplets. PMID- 6266676 TI - Macrophage-mediated cytolysis off erythrocytes in the guinea pig. I. Activation by stimulators of the oxidative burst. PMID- 6266677 TI - [Levels of Epstein-Barr virus antibodies in the serum of children with acute lymphoblastic leukemia]. PMID- 6266675 TI - Activation of macrophage adenylate cyclase by stimulants of the oxidative burst and by arachidonic acid--two distinct mechanisms. PMID- 6266678 TI - [A study of children repeatedly negative after smallpox vaccination]. PMID- 6266679 TI - [Insular tumours of the pancreas (author's transl)]. AB - The use of immunohistochemistry and radioimmunological assay of the pancreatic polypeptides in the plasma has contributed substantial advances to the histophysiopathology and preoperative diagnosis of tumours of the endocrine pancreas and the related functional syndromes. Consequently, in addition to furthering knowledge on clinical pictures already known for some time, it has been possible to define new categories of the disease which were previously misunderstood or confused with others. The physiopathology and diagnostic methodology (clinical, biohumoral and instrumental) of each main known syndrome (insulinoma, Zollinger-Ellison Syndrome, Verner-Morrison disease and glucagonoma) are described in detail; there are notes on hormonal syndromes that are not fully known and which constitute a field of research in evolution (pluriendocrine and carcinoid syndromes, polypeptidoma, somatostatinoma, nesidioblastosis). The problems of preoperative preparation, intraoperative diagnostic tactics and surgical technique are illustrated. Lastly the possibilities of alternative therapeutic treatment are outlined. PMID- 6266680 TI - [Bilateral carcinoma of the breast (personal experience) (author's transl)]. PMID- 6266681 TI - [Sebaceous carcinoma and extra-mammary Paget's disease of the eyelid]. PMID- 6266682 TI - Seasonal fluctuations in the occurrence of enterotoxigenic bacteria and rotavirus in paediatric diarrhoea in Addis Ababa. AB - This study (March 1977-February 1978) was performed at the Ethio-Swedish Pediatric Clinic, Addis Ababa, to determine whether there were any seasonal fluctuations in the occurrence of diarrhoea associated with enterotoxigenic enterobacteria (ETEB), rotavirus and two parasites (Giardia lamblia and Entamoeba histolytica).A total of 1161 children (962 patients and 199 controls) were investigated. ETEB were isolated in 12.2% of the patients and 4.5% of the controls, rotavirus in 27.8% and 8%, and parasites in 6.8% and 1%, respectively. There is a statistically significant difference in the isolation rates between patients and controls (P<0.001 for rotavirus, P<0.01 for ETEB and parasites). Rotavirus was most prevalent in the 7-12 months age group and ETEB during the second year of life, while parasites showed a continuous increase with age.Two peaks in the occurrence of ETEB were found during the year, the first in August (32.6%), the second in January (19.2%). Two peaks for rotavirus though not as distinct as for ETEB, were seen in June (42.7%) and November (36.4%). The isolation rate of parasites showed no consistent pattern during the year.This study suggests a seasonal occurrence of ETEB and rotavirus but with no apparent correlation to climatological factors. PMID- 6266683 TI - The use of four-drug combination chemotherapy (D.A.V.E.) in the treatment of advanced Wilms' tumour. AB - A study was begun in 1971 at St. Bartholomew's Hospital with a combination of 4 drugs, dactinomycin (actinomycin D), adriamycin, vincristine and Endoxan (cyclophosphamide) (D.A.V.E.), together with surgery and radiation, in the treatment of stage III and stage IV Wilms' tumour. Seventy-one percent of the children treated achieved complete response. The median survival from diagnosis was 19 months, and in those children achieving complete response the median disease-free survival has not yet been reached. Toxicity was not a serious problem. The study group is compared with a group of children treated at this hospital before 1971. There is an improved survival in the children treated with D.A.V.E. Children who have relapsed with stage I or stage II disease may also respond. This four-drug combination was well tolerated and effective, and confirms recent experience suggesting that intensive multiple-drug regimens may be curative even in advanced disease. PMID- 6266684 TI - Corneal ulceration following measles in malnourished Nigerian children. PMID- 6266685 TI - The relation between reduced protein degradation and elevated adenosine 3',5' monophosphate in isolated rat atria. PMID- 6266686 TI - Alterations in aldosterone biosynthesis in essential hypertensives. AB - We studied hypertensives with decreased adrenal responsiveness to infused angiotensin II (AII) to assess their responsiveness to other aldosterone secretagogues, ACTH and potassium, which are thought to stimulate aldosterone synthesis in sites different from one another and from AII. All subjects, following sodium restriction, received an infusion of AII in increasing doses (0.1-3 ng/kg per min). The increment in aldosterone between control and the highest infusion dose divided by the increment in plasma AII was used as the index of adrenal responsiveness. All normotensive controls (NC) had a ratio greater than 0.5. Hypertensives with a normal ratio were designated normal responders (NR) and those with a lower ratio were abnormal responders (AbR). The slope of the regression line between aldosterone and AII was significantly less for the AbR (0.02 +/- 0.04) than for the NR (1.20 +/- 0.02, P less than 0.001) and the NC (1.00 +/- 0.03, P less than 0.001) groups. During infusion of cosyntropin in increasing doses (0.05-1.5 mIU/kg per 30 min), the aldosterone response of the AbR was significantly less than that of the NR (P less than 0.016) or the NC (P less than 0.05) groups. Similarly, after infusion of potassium (0.33 mEq/min), the increment in aldosterone in the AbR group (7.6 +/- 2.2 ng/dl) was significantly less than that in the NR (14.2 +/- 2.5 ng/dl, P less than 0.05) and the NC (18 +/- 5 ng/dl, P less than 0.05) groups. Thus hypertensives with decreased aldosterone responsiveness to infused AII also had decreased responsiveness to infused ACTH and potassium, suggesting that their defect lies in the intracellular aldosterone biosynthetic pathway. PMID- 6266687 TI - Effects of chronic digitalization on cardiac and renal Na+ + K+-dependent adenosine triphosphate activity and circulating catecholamines in the dog. AB - To extend our understanding of the mechanism of action of digitalis drugs, we studied electrocardiograms (ECGs), renal function, plasma concentrations of catecholamines, and myocardial and renal Na+ + K+-dependent adenosine triphosphate (Na+ + K+ ATPase) activity in chronically digitalized dogs. Five healthy, male, mongrel dogs received a therapeutic regimen of digoxin (0.1 mg/kg on day 1 in three divided doses followed by 0.025 mg/kg per day) orally for 2-4 months. This resulted in plasma digoxin concentrations of 1.1 to 4.7 ng/ml as determined by radioimmunoassay. Six control dogs received daily gelatin capsules by mouth. ECGs monitored throughout the study showed no changes. Digitalized dogs had elevated plasma norepinephrine concentrations (347 vs. 137 pg/ml in controls) and no change in plasma epinephrine concentrations. Digitalized dogs had elevated glomerular filtration rates (0.74 vs. 0.94 ml/min per g of kidney) without significant changes in renal handling of electrolytes and water. All of the above studies were done without the aid of restraining drugs or infusions. The animals were killed with an overdose of pentobarbital for in vitro studies. In digitalized dogs, microsomal Na+ + K+ ATPase-specific activity was 26 to 33% lower in the renal cortex, medulla, and papilla, and 46% lower in the cardiac left ventricle than in control dogs. Digitalization did not alter the osmolalities of renal tissues. We conclude that chronic reduction Na+ + K+ ATPase activity by one-third dose does not cause abnormalities in renal handling of electrolytes and water, and inhibition of Na+ + K+ ATPase in the left ventricular muscle by one-half is associated with no obvious ECG changes in the dog. Further, elevated plasma norepinephrine concentrations may contribute to both the therapeutic and the toxic effects of digitalis. PMID- 6266688 TI - EPR and fluorescence depolarization studies on bovine cardiac myosin. AB - To test for possible differences in local conformation and S1 flexibility, bovine cardiac and rabbit skeletal myosins were labeled with a fluorophore (1,5-IAEDANS) and a spin label having iodoacetamide reactivity. The marked activation of the Ca2+-ATPase (6- to 8-fold) and inhibition of the K+ (EDTA)-ATPase (80-90%) by both labels indicated specific labeling of the fast-reacting thiols (SH1) of both myosins. Fluorescence depolarization studies of 1,5-IAEDANS-labeled cardiac myosin indicated that, like skeletal myosin, the SI moieties of cardiac myosin exhibit considerable segmental flexibility with respect to the rod portion of the molecule. This indicates that segmental flexibility may be a property of all myosins. Cardiac and skeletal myosins immobilized spin labels to approximately the same extent, indicating a similarity in steric restraints around the SH1 thiol of the two myosins. The magnitude of the changes in spin label mobility accompanying binding of MgADP and hydrolysis of MgATP was reduced in cardiac myosin relative to skeletal myosin. This suggests that the lower catalytic center activity of cardiac myosin is associated with more restricted conformational changes accompanying formation of M.ADP and M.ADP.Pi. From measurements of spin label mobility, the affinity of cardiac and skeletal myosin for ADP were similar: Kd (ADP) = 7 microM, n = 1.6. The EPR spectrum of spin labels attached to cardiac and skeletal myosin showed similar saturation effects upon actin binding indicating immobilization of myosin heads occurs with both proteins. PMID- 6266689 TI - Regulation of vascular angiotensin II receptors in the rat during altered sodium intake. PMID- 6266690 TI - Comments on "identification and characterization of the high affinity vascular angiotensin II receptor in rat mesenteric artery". PMID- 6266691 TI - Acute regional circulatory and renal hemodynamic effects of converting-enzyme inhibition in patients with congestive heart failure. AB - The acute effects of the angiotensin converting-enzyme inhibitor captopril on regional blood flow, renal hemodynamics and sodium excretion were studied in 12 patients with severe congestive heart failure. Converting-enzyme inhibition decreased systemic vascular resistance by 27% and increased cardiac index by 16%. Estimated hepatic blood flow decreased 17%, but renal blood flow increased 60%. The ratio of renal-systemic blood flow increased from 0.10 +/- 0.01 to 0.14 +/- 0.02 (p = 0.031). Although renal plasma flow increased from 202.8 +/- 28.8 to 323.7 +/- 42.7 ml/min (p less than 0.008), the glomerular filtration rate did not change significantly from the mean pretreatment value of 82.1 +/- 12.3 ml/min. The filtration fraction decreased from 41.3 +/- 3.8% to 33.4 +/- 4.5% (p = 0.050), while urinary sodium excretion doubled, from 34.5 +/- 9.6 to 68.2 +/- 19.6 muEq/min. The plasma renin activity increased from 12.6 +/- 5.0 to 29.9 +/- 8.4 ng/ml/hr (p = 0.030) as plasma aldosterone concentration decreased from 30.5 +/- 6.5 to 11.3 4/- 1.2 ng/dl (p = 0.010) and norepinephrine concentrations decreased from 774 +/- 105 to 618 +/- 85 pg/ml (p = 0.020). We conclude that converting-enzyme inhibition reverses renal vasoconstriction in congestive heart failure and redistributes regional blood flow. The natriuresis may be mediated by one or more of the following: improved renal plasma flow, reduction in filtration fraction, suppression of hyperaldosteronism, and lowering of circulatory catecholamine concentrations. PMID- 6266692 TI - Radionuclide quantitation of right-to-left intracardiac shunts in children. AB - A simple, noninvasive method for measurement of right-to-left intracardiac shunts would enhance the management of patients with congenital heart disease. This study describes application of data processing techniques used previously in dye indicator curves to data recorded during the initial transit of radioactive bolus through the central circulation. Radionuclide angiocardiograms were performed in 20 children, mean age 30 months, immediately after cardiac catheterization for congenital heart disease. The radionuclide data recorded over the carotid artery were used to replace arterial sampling required for dye indicators, and forward triangles were fitted to calculate the right-to-left shunt in an approach similar to that of Wood for indicator-dilution curves. Ten of the children had right-to left shunts by Fick and radionuclide measurement, and 10 of the children with septal defects had no right-to-left shunt by either technique. Both the radionuclide and Fick measurements correlated well (r = 0.95). Therefore, radionuclide angiocardiographic data may be used for accurate calculation of right-to-left shunts in small children, eliminating the need for arterial sampling. PMID- 6266693 TI - Use of equilibrium (gated) radionuclide ventriculography to quantitate left ventricular output in patients with and without left-sided valvular regurgitation. AB - We examined the accuracy with which left ventricular output can be estimated by equilibrium radionuclide ventriculography. After red blood cells were labeled in vivo, we measured left ventricular end-diastolic and end-systolic count rates and the count rate in 5 ml of the patient's blood. After estimating the average ratio of counting efficiency for the left ventricle to counting efficiency for the blood sample (Elv/Es) in six patients, we calculated left ventricular output in 26 other patients as (left ventricular activity ejected per minute divided by activity per liter of blood) divided by the previously estimated Elv/Es. Radionuclide left ventricular output closely approximated Fick cardiac output (r = 0.94) in patients without mitral or aortic regurgitation and exceeded Fick cardiac output in all patients with valvular regurgitation. Regurgitant fraction, calculated as the difference between the radionuclide and Fick outputs divided by the radionuclide output, correlated with the severity of of regurgitation as assessed angiographically. The equilibrium radionuclide ventriculogram is an excellent means for noninvasive estimation of left ventricular output. PMID- 6266694 TI - Accuracy of diagnosis of coronary artery disease by radionuclide management of left ventricular function during rest and exercise. AB - Rest and exercise radionuclide angiocardiographic measurements of left ventricular function were obtained in 496 patients who underwent cardiac catheterization for chest pain. Two hundred forty-eight of these patients also had an exercise treadmill test. An ejection fraction less than 50% was the abnormality of resting left ventricular function that provided the greatest diagnostic information. In patients with normal resting left ventricular function, exercise abnormalities that were optimal for diagnosis of coronary artery disease were an injection fraction at least 6% less than predicted, an increase greater than 20 ml in end-systolic volume and the appearance of an exercise-induced wall motion abnormality. The sensitivity and specificity of the test were lower in patients who were taking propranolol at the time of study and in patients who failed to achieve an adequate exercise end point. In the 387 patients with an optimal study, the test had a sensitivity of 90% and a specificity of 58%. Radionuclide angiocardiography was more sensitive and less specific than the exercise treadmill test. The high degree of sensitivity of the radionuclide test suggests that it is most appropriately applied to patient groups with a high prevalence of disease, including those considered for cardiac catheterization. PMID- 6266695 TI - Methods for ligand-receptor assays in clinical chemistry. AB - This is intended to be a practical review for the clinical chemist of the laboratory procedures most commonly used to quantitate hormone receptors in various cellular fractions. These procedures include use of charcoal adsorption and hydroxylapatite for intracellular receptors and of centrifugation and filtration for membrane receptors. We discuss the use of the Scatchard analysis to establish the steroid-receptor affinity and the quantity of steroid-receptor binding sites. Both pre- and post-labeled sucrose density gradient methods are outlined. One section is devoted to the direct and indirect methods used in nuclear "exchange" assays. Basic theory underlying each assay is presented, but, more importantly, we assess the advantages and disadvantages of each procedure. On the basis of this information, one may decide which assay is best suited for a particular laboratory and (or) specimen. PMID- 6266696 TI - Ion effects in measurement of ionized calcium with a calcium-selective electrode. AB - We examined the performance characteristics of an improved electrode for measurement of ionized calcium (Orion Research, Inc.) with respect to interferences by Na+, K+, Li+, Mg2+, and H+, as well as the effect of changes in ionic strength and osmolality. At physiologically observed concentrations, all ions except Na+ insignificantly affected ionized-calcium measurements. The decrease in ionized Ca2+ with increased Na+ concentration is caused by the increase in ionic strength and the associated decrease in Ca2+ activity. Sodium had no significant direct effect in concentrations below 250 mmol/L. A previously published (Clin. Chem. 23: 690, 1977) equation for the Na+ correction is invalid for this improved electrode. Changes in osmotic pressure negligibly affect electrode response. Significant changes in ionic strength, as would be observed in severe hypo- and hypernatremic sera, increase or decrease, respectively, values for ionized calcium by changing Ca2+ activity. With aqueous Ca2+ solutions, changes of less than or equal to 3% were observed for Na+ concentrations that deviate from 140 mmol/L by not more than 20 mmol/L. Because the calcium ion activity is considered to be the physiologically important variable, we suggest that no correlation be made for ionic strength effects. PMID- 6266697 TI - Interference of EDTA in determinations of c-AMP and c-GMP in plasma by radioimmunoassay. PMID- 6266698 TI - Evaluation of the CIS-Sorin corticotropin kit. PMID- 6266699 TI - Adrenocortical function in vitiligo. PMID- 6266700 TI - The determination of platinum in biological fluid by means of graphite furnace atomic absorption spectrometry. PMID- 6266701 TI - Adrenocortical tumour in untreated congenital adrenocortical hyperplasia associated with inadequate ACTH suppressibility. AB - Data are presented concerning a 60-year-old woman with untreated congenital adrenocortical hyperplasia due to 21-hydroxylase deficiency, who presented with a tumour of the left adrenal gland. Steroid excretion was partly suppressed with dexamethasone. After removal of the tumour, the excretion of several steroid fractions decreased substantially, but suppression by dexamethasone remained inadequate. Preoperatively, plasma ACTh was elevated in the afternoon and decreased only slightly after dexamethasone administration. After surgery, cortisol secretion decreased markedly, whereas ACTH dysregulation became more prominent. Negative feedback failure precluded the use of normal suppressive therapy with low doses of glucocorticosteroids and led to the therapeutic removal of the right adrenal gland, which showed histological signs of nodular hyperplasia. PMID- 6266702 TI - Vitamin D resistant rickets with alopecia: a form of end organ resistance to 1,25 dihydroxy vitamin D. AB - A 4-year-old girl presented with severe clinical and radiological rickets, and alopecia since the age of 1 year. Laboratory studies revealed: hypocalcaemia, hypophosphataemia, secondary hyperparathyroidism, abnormally low intestinal calcium absorption, and markedly elevated circulating 1,25(OH)2D3 levels. A normal calcaemic response to parathyroid extract was obtained. Treatment attempts with vitamin D2, 1 alpha (OH)D3 and 1,25(OH)2D3 were totally ineffective. Intestinal resistance to the action of 1,25(OH)2D3 appeared well established in this case. Refractoriness of bone to this hormone seems less certain. From this new entity of 'Vitamin D resistant rickets due to end organ unresponsiveness', six cases have been hitherto reported in the literature. However, only two have enough resemblance to our case, to constitute a distinct and well defined nosologic subunit. The molecular basis of this disorder(s) remains to be elucidated. PMID- 6266703 TI - Lack of response of 1,25-dihydroxycholecalciferol to exogenous parathyroid hormone in a patient with treated pseudohypoparathyroidism. AB - The response of serum 1,25-dihydroxycholecalciferol (1,25-OH2CC) concentration to the administration of parathyroid extract (PTE) was studied in a patient with pseudohypoparathyroidism (PHP) type 1, 3 days after withdrawal of dihydrotachysterol (DHT) treatment. The patient had had a normal serum calcium (Ca), phosphorus (P) and immunoreactive parathyroid hormone (iPTH) level on DHT for 6 years. After PTE administration no rise of the 1,25-OH2CC concentration and no response of urinary cAMP and P were seen. PMID- 6266704 TI - beta-lipotrophin and beta-endorphin plasma levels during pregnancy. AB - beta-lipotrophin (beta-LPH) and beta-endorphin (beta-EP) plasma levels were measured by radioimmunoassay after glass powder extraction and Sephadex G-75 column chromatography in plasma samples from controls (ten healthy males and twenty-six young women in early follicular phase), from eighty-two pregnant women in weeks 9-40 after their last menstrual period, from nine women just after delivery and the cord blood of their neonates, in fifteen mixed cord blood samples and in seven amniotic fluid samples obtained by amniocentesis. No sex differences were found in beta-LPH (120.6 +/- 8.5 pg/ml) or beta-EP (31.1 +/- 2.4 pg/ml) plasma levels or in their molar ratio (1.34 +/- 0.09) (MR). beta-LPH plasma levels increased in early pregnancy (13-16 weeks) (185.0 +/- 27.1 pg/ml) and remained high until weeks 21-24, then declining to levels similar to those of controls. beta-EP plasma levels were significantly depressed in weeks 9-12 (20.7 +/- 5.3 pg/ml), subsequently increasing to a maximum at weeks 36-37 (42.7 +/- 6.8 pg/ml). beta-LPH/beta-EP molar ratio was about double normal in early pregnancy and decreased to normal in the second half. The present data indicate that beta LPH and beta-EP present different patterns throughout pregnancy and that beta-EP levels increase progressively, reaching the highest concentrations at term. At delivery, both beta-LPH and beta-EP showed maximum values (beta-LPH: 230.2 +/- 20.4 pg/ml; beta-EP: 78.0 +/- 7.4 pg/ml) and a MR of 1.02 +/- 0.10 indicating that stressful situations, such as labour, stimulate a simultaneous rise in beta LPH and beta-EP plasma levels. Cord blood specimens showed a wide range of values (beta-LPH:75-347 pg/ml; beta-EP: 16-287 pg/ml) with a MR of 1.21 +/- 0.14. Amniotic fluid samples obtained late in the third trimester of pregnancy were characterized by beta-LPH levels of 119.4 +/- 26.4 pg/ml and beta-EP levels of 29.6 +/- 7.5 pg/ml. PMID- 6266705 TI - [Basic and clinical study of hCG--beta measured by hCG-beta test kit (author's transl)]. PMID- 6266706 TI - [Biochemical properties of PRL receptor (author's transl)]. PMID- 6266707 TI - [LH receptor and modulation of luteal function (author's transl)]. PMID- 6266708 TI - [Some problems on hormone receptors (author's transl)]. PMID- 6266709 TI - [Change in follicle-stimulating hormone receptors and its hormonal regulation in the developing testis (author's transl)]. PMID- 6266710 TI - [Cyclic-AMP-dependent protein kinase activity in the soluble thyrotropin receptor complex (author's transl)]. PMID- 6266711 TI - [Human thyroid TSH receptors and adenylate cyclase (author's transl)]. PMID- 6266712 TI - [Properties of thyrotropin releasing hormone (TRH) receptors in CNS (author's transl)]. PMID- 6266714 TI - [Characteristics of hepatic GH receptor from rabbit (author's transl)]. PMID- 6266713 TI - [Thyroid hormone receptors (author's transl)]. PMID- 6266715 TI - [Hormone receptor diseases (author's transl)]. PMID- 6266716 TI - [1,25-dihydroxyvitamin D3 synthesis in pseudohypoparathyroidism (author's transl)]. PMID- 6266717 TI - [Pseudohypoparathyroidism. Receptor on human lymphocytes (author's transl)]. PMID- 6266718 TI - [Characterization of cAMP-dependent protein kinases by photoaffinity labeling (author's transl)]. PMID- 6266719 TI - [Thyrotropin receptors in normal and pathological human thyroid tissues (author's transl)]. PMID- 6266721 TI - Pathological factors influencing excision of tumours in the head and neck. Part II. PMID- 6266720 TI - Primary carcinoma of the trachea. AB - Five cases of primary carcinoma of the trachea are summarized together with a review of 97 cases recorded at the Birmingham Cancer Registry between 1957 and 1974. Squamous cell carcinoma is the most frequent type (46.4%) followed by anaplastic and oat cell carcinoma (18.5%). The annual incidence rate is 0.15 per 100 000 in males and 0.06 per 100 000 in females. The mean age at presentation is 60.08 years and 63.89 years for males and females respectively. Although there has been an increase in the number of cases reported over this period, the increase in larynx (43%) and trachea (50%) has not kept pace with that for bronchial carcinoma (85%). Some experimental studies in animals and the results of treatment in 97 cases from the Cancer Registry are reported. A brief summary of methods of treatment for carcinoma of the trachea is included. In suitable cases, primary surgery with direct anastomosis offers the best survival rates, although the overall survival rate is poor. PMID- 6266722 TI - Institute of Laryngology and Otology clinico-pathological meeting. Cytomegalovirus and congenital hearing loss. PMID- 6266723 TI - Detection of anti-platelet antibodies in patients with idiopathic thrombocytopenic purpura (ITP) and in patients with rubella and herpes group viral infections. AB - A highly sensitive enzyme-linked immunosorbent assay (ELISA) technique was observed for serological detection of antibodies against platelets. A covalently bound to Sepharose CL-4B was used to enrich sera in the IgG3 subclass of antibodies. The ELISA procedure as applied to detect anti-platelet antibodies in patients with herpes or rubella viral infections and in patients with idiopathic thrombocytopenic purpura (ITP). Twenty-eight sera from 13 thrombocytopenic patients showed high levels of anti-platelet antibodies. Two splenectomized patients in remission became negative for anti-platelet antibodies. Seventy-four sera from patients with serological diagnosis of herpes group viral infections comprising 10 cases of cytomegalovirus, nine cases of varicella or zoster, six cases of herpes simplex and four cases of Epstein-Barr virus were examined for the presence of anti-platelet antibodies. Except for two patients with varicella and zoster and one patient with rubella infection, all cases examined showed positive titres of anti-platelet antibodies. Sera from a group of 51 healthy controls were evaluated for anti-platelet antibodies. Forty-nine (96%) were negative (less than 40), whereas the other two were only slightly positive. PMID- 6266724 TI - Evidence for the presence of double-stranded polynucleotides inthe neutrophil inclusions of circulating neutrophils and those which form in the presence of SLE sera. PMID- 6266725 TI - Migration of null lymphocytes to murine sarcoma virus-induced tumors. PMID- 6266726 TI - Correlation between immunosuppressive agents from media of human malignant melanoma cell cultures and from human serum. PMID- 6266727 TI - Uncontrollable hypertension in patients on hemodialysis: long-term treatment with captopril and salt subtraction. AB - It has been suggested that an inappropriate relationship between renin and exchangeable sodium is responsible for the hypertension of patients with chronic renal failure. Long-term blockade of the renin system by captopril made it possible to test this hypothesis in 8 patients on maintenance hemodialysis. Captopril was administered orally in 2 daily doses of 25 to 200 mg. Previously, blood pressure averaged 179/105 +/- 6/3 (mean +/- SEM) pre- and 182/103 +/- 7/3 mm HG post-dialysis, despite intensive ultrafiltration and conventional antihypertensive therapy. The 4 patients with the highest plasma renin activity normalized their blood pressure with captopril alone, whereas in the 4 remaining patients, captopril therapy was complemented by salt subtraction which consisted in replacement of 1-2 liters of ultrafiltrate by an equal volume of 5% dextrose until blood pressure was controlled. After an average treatment period of 5 months, blood pressure of all 8 patients was reduced to 134/76 +/- 7/5 mm Hg (P less than 0.001) pre- and 144/81 +/- 9/5 mm Hg (P less than 0.001) post-dialysis without a significant change in body weight. The present data suggest that captopril alone or combined with salt subtraction normalizes blood pressure of patients on chronic hemodialysis with so called uncontrollable hypertension. PMID- 6266728 TI - [Familial amyloid neuropathy with late onset and benign course (author's transl)]. PMID- 6266729 TI - [Arsenical polyneuropathy. Report of two cases (author's transl)]. PMID- 6266730 TI - [Choroid plexus scintigraphy: a clinical and experimental study (author's transl)]. PMID- 6266731 TI - Failure to diagnose cardiac treatment rejection with Tc99m-PYP images. AB - The possibility of diagnosing transplant rejection using Tc-99m-PYP imaging was examined in 12 cardiac transplant recipients. Two patients were studied on two occasions. The presence or absence of active rejection was established by endomyocardial biopsy. The intensity and pattern of myocardial uptake of the tracer did not differ significantly in the two patients studied at the time of rejection compared to the remainder. It is concluded that a single Tc-99m-PYP study cannot be used to diagnose cardiac transplant rejection. PMID- 6266733 TI - Effect of sodium intake on angiotensin-converting enzyme activity of aorta in rats. AB - 1. The effect of sodium intake on angiotensin-converting enzyme activity in subcellular fractions of aorta (homogenate, mitochondria, microsomes and supernatant) was studied in normotensive and spontaneously hypertensive rats. 2. Angiotensin-converting enzyme activity was extremely high in the supernatant fraction in normotensive and spontaneously hypertensive rats. 3. Total converting enzyme activity in spontaneously hypertensive rats was 34% higher than that in normotensive rats. 4. Increased sodium intake resulted in a marked reduction, almost to zero, of converting enzyme activity in each fraction of aorta in normotensive and spontaneously hypertensive rats. 5. Converting enzyme, widely distributed in subcellular fractions of the aorta, may play a possible role in the local control of vascular tone. It is likely that sodium intake inhibits production of the enzyme in vascular tissue. PMID- 6266732 TI - The neurogenic bladder. PMID- 6266734 TI - Cardiac sympathetic nerves as the final common pathway in the induction of adaptive cardiac hypertrophy. PMID- 6266735 TI - Effect on blood lipids and haemostasis of a supplement of cod-liver oil, rich in eicosapentaenoic and docosahexaenoic acids, in healthy young men. AB - 1. Twelve healthy male subjects took a daily supplement of 20 ml of cod-liver oil for 6 weeks. This provided 1.8 g of eicosapentaenoic acid (20:5 omega 3) and 2.2 g of docosahexaenoic acid (22:6 omega 3). The effects of the supplement on blood lipids, haemostatic variables, bleeding time and plasma vitamin A and carotene were studied. In seven subjects platelet aggregation induced by adenosine 5' pyrophosphate (ADP) was also studied. 2. The proportions of 20: 5 omega 3 and 22: 6 omega 3 in platelet and erythrocyte phosphoglycerides were substantially increased by the supplement mainly at the expense of omega 6 polyunsaturated fatty acids. 3. Mean plasma triglyceride concentrations were reduced and those of high-density-lipoprotein (HDL) cholesterol were increased by the supplement. 4. The mean bleeding time was significantly prolonged after 3 weeks of taking the supplement, but had returned to the presupplementation value 5 weeks after withdrawal of the supplement. 5. The maximum estimated response to platelet aggregation induced by ADP was increased by the supplement. 6. The mean levels of antithrombin III (immunological) and blood pressure were lower at the end of the period of supplementation and remained so 5 weeks after withdrawal of the supplement. No significant changes in other variables were noted. PMID- 6266736 TI - Summary. PMID- 6266737 TI - Movable genetic elements. PMID- 6266738 TI - Instability among the components of a regulatory element transposon in maize. PMID- 6266739 TI - Regulation of the enzyme UFGT by the controlling element Ds in bz-m4, an unstable mutant in maize. PMID- 6266740 TI - Detection of changes in maize DNA at the shrunken locus due to the intervention of Ds elements. PMID- 6266742 TI - The role of controlling elements in the instability of flower color in Antirrhinum majus and Impatiens balsamina. PMID- 6266741 TI - Controlling elements at the opaque-2 locus of maize: their involvement in the origin of spontaneous mutation. PMID- 6266743 TI - Molecular genetic analysis of Klebsiella pneumoniae nitrogen-fixation (nif) genes. PMID- 6266744 TI - Genetic instability in Ascobolus immersus: modalities of back-mutations, intragenic mapping of unstable sites, and unstable insertion. Preliminary biochemical data. PMID- 6266745 TI - A novel dominant mutant allele at the white locus of Drosophila melanogaster is mutable. PMID- 6266746 TI - Derivation-dependent distribution of insertion sites for a Drosophila transposon. PMID- 6266747 TI - Transpositions, mutable genes, and the dispersed gene family Dm225 in Drosophila melanogaster. PMID- 6266748 TI - Site-specific intrachromosomal rearrangements in Drosophila melanogaster: cytogenetic evidence for transposable elements. PMID- 6266749 TI - Hybrid dysgenesis in Drosophila and the Stochastic loss hypothesis. PMID- 6266750 TI - Transposable elements involving the his4 region of yeast. PMID- 6266751 TI - Transposable elements (Ty) in yeast. PMID- 6266752 TI - Studies on the transposable element Ty1 of yeast. I. RNA homologous to Ty1. II. Recombination and expression of Ty1 and adjacent sequences. PMID- 6266753 TI - Studies on transposable elements in yeast. I. ROAM mutations causing increased expression of yeast genes: their activation by signals directed toward conjugation functions and their formation by insertion of Ty1 repetitive elements. II. deletions, duplications, and transpositions of the COR segment that encompasses the structural gene of yeast iso-1-cytochrome c. PMID- 6266754 TI - Characterization of the yeast mobile element Ty1. PMID- 6266755 TI - Copia-like transposable elements in the Drosophila genome. PMID- 6266756 TI - Mobile dispersed genetic elements and other middle repetitive DNA sequences in the genomes of Drosophila and mouse: transcription and biological significance. PMID- 6266758 TI - Structure and expression of ribosomal RNA genes of Drosophila melanogaster interrupted by type-2 insertions. PMID- 6266757 TI - General properties of mobile dispersed genetic elements in Drosophila melanogaster. PMID- 6266759 TI - Selection and transposition of mobile dispersed genes in Drosophila melanogaster. PMID- 6266761 TI - The long terminal repeat of Moloney sarcoma provirus. PMID- 6266760 TI - Integration and activity of mammary tumor virus genes: regulation by hormone receptors and chromosomal position. PMID- 6266762 TI - Moloney murine leukemia virus is a transposon: nucleotide sequence analysis identifies genes and replication details. PMID- 6266763 TI - Structure of cloned retroviral circular DNAs: implications for virus integration. PMID- 6266764 TI - Evolution of retroviruses from cellular movable genetic elements. PMID- 6266766 TI - Structural analogies among avian retroviral DNAs and transposable elements. PMID- 6266765 TI - DNA intermediates in the replication of retroviruses are structurally (and perhaps functionally) related to transposable elements. PMID- 6266767 TI - Genomic rearrangements and tumor-forming potential in an SV40-transformed mouse cell line and its hybrid and cybrid progeny. PMID- 6266768 TI - Conserved sex-chromosome-associated nucleotide sequences in eukaryotes. PMID- 6266769 TI - The organization of Drosophila melanogaster histone genes. PMID- 6266770 TI - Pattern of switching and fate of the replaced cassette in yeast mating-type interconversion. PMID- 6266771 TI - Irregular transpositions of mating-type genes in yeast. PMID- 6266772 TI - Treatment adherence after brief hospitalization. PMID- 6266773 TI - CT findings in multicentric glioblastoma: diagnostic-pathologic correlation. AB - Computerized cranial tomography (CCT) and angiographic findings in three cases of multicentric glioblastoma are reported. Differentiation of multicentric glioblastoma from diffuse metastatic deposits or multiple abscesses can be difficult with CCT. Apart from demonstrating a mass effect in one case and tumor neovascularity in the second case, angiography did not provide additional helpful information. The pathological diagnoses of these lesions were confirmed by biopsy and subsequent autopsy. Pathological differentiation of the multifocal or multicentric nature of the glioblastoma can be made only at autopsy. PMID- 6266774 TI - Bactericidal activity of erythromycin in the respiratory system. AB - In vivo and in vitro studies were carried out to assess tha levels in bronchial mucus of ampicillin, amoxycillin, bacampicillin, cefotaxime and erythromycin, and to compare their minimum bactericidal concentrations and killing rate against hospital strains of Staphylococcus aureus, Streptococcus pyogenes and Haemophilus influenzae. Both the percentage ratios of serum/mucus concentration peaks and of serum/mucus area under the concentration time curve values were higher for erythromycin than for the other antibiotics. Determination of the minimum bactericidal concentrations showed that the bacterial strains were sensitive to small quantities of erythromycin, and the time necessary to sterilize inocula varied from 4 to 16 hours. PMID- 6266775 TI - Tumors of the retroperitoneum. PMID- 6266776 TI - Leishmaniasis recidivans treated with sodium stibogluconate. AB - Two cases of leishmaniasis recidivans of twenty years' duration were treated intravenously with sodium stibogluconate (Pentostam) with good results. Before treatment, histologic examination of a biopsy specimen revealed many Leishman Donovan (LD) bodies. After treatment, repeated biopsies done in one of the cases revealed only scar tissue. We recommended treatment with sodium stibogluconate in cases of leishmaniasis recidivans, although an ideal treatment for this condition still does not exist. PMID- 6266777 TI - Detection of serum antibody to herpes simplex virus type I by enzyme-linked immunosorbent assay (ELISA). AB - For setting up an Enzyme-Linked Immunosorbent Assay (ELISA) to detect antibodies to herpes simplex virus type 1 (HSV-1), the virus was propagated in Vero cells and partially purified by sonification and ultracentrifugation on 30% sucrose solution. DEAE ion-exchange column chromatography was used for purification of goat anti-human IgG serum. The anti-human IgG immune serum and alkaline phosphatase were conjugated by glutaraldehyde method. ELISA test was performed by reacting HSV-1 antigen coated in polystyrene tubes with serum specimens and enzyme-IgG conjugates. The color produced by enzyme-substrate reaction was measured on a spectrophotometer. The results obtained by the ELISA had a good agreement with those obtained by a standard neutralization procedure on 119 serum specimens tested for antibody to HSV-1. PMID- 6266779 TI - Nucleotide sequence variants of Rattus norvegicus mitochondrial DNA. AB - The mitochondrial DNA (mtDNA) molecules of different albino, domesticated rats (Rattus norvegicus) of the SASCO colony are of two kinds (SASCO-1 and SASCO-2) in regard to their sensitivity at certain sites to a number of restriction enzymes. MtDNA molecules from Utah wild R. norvegicus (Wild-UT) have sensitivities to restriction enzymes which differ at some sites from either SASCO-1 or SASCO-2 mtDNA molecules. Four single nucleotide differences were found among the HindIII F fragments (169 nucleotides) of SASCO-1, SASCO-2, and Wild-UT mtDNAs. Arguments are presented in favor of the interpretation that each variant nucleotide is the third nucleotide of the codon containing it, and that none of the four differences would result in a difference in the respective amino acid translated. PMID- 6266778 TI - Analysis of a dispersed repetitive DNA sequence in isogenic lines of Drosophila. AB - The location of sequences homologous to a cloned D. melanogaster DNA segment, Dm 25, has been examined in polytene chromosomes by hybridization in situ. Dm 25 localizes to multiple sites and shows variation in patterns between different strains and among individuals within wild-type laboratory strains. Analysis of numerous geographically distinct isogenic lines suggests that Dm 25 patterns are determined by germ-line factors and are not the product of strictly somatic events. In general there is wide variation in Dm 25 patterns among different lines, but a significant number of sites are common to two or more distinct lines. Hybridization to restriction digests of genomic DNA suggests that Dm 25 is a moderately repetitive, conserved sequence whose copies are dispersed throughout the genome. Analysis of species other than melanogaster indicates a significant divergence in structure of sequences homologous to Dm 25 as well as a drastic reduction in amount of homology to the melanogaster sequence. PMID- 6266780 TI - Nontranscribed spacers in Drosophila ribosomal DNA. AB - Ribosomal DNA nontranscribed spacers in Drosophila virilis DNA have been examined in some detail by restriction site analysis of cloned segments of rDNA, nucleic acid hybridizations involving unfractionated rDNA, and base composition estimates. The overall G + C content of the spacer is 27--28%; this compares with 39% for rDNA as a whole, 40% for main band DNA, and 26% for the D. virilis satellites. Much of the spacer is comprised of 0.25 kb repeats revealed by digestion with Msp I, Fnu DII or Rsd I, which terminate very near the beginning of the template for the ribosomal RNA precursor. The spacers are heterogeneous in length among rDNA repeats, and this is largely accounted for by variation among rDNA units in the number of 0.25 kb elements per spacer. Despite its high A + T content and the repetitive nature of much of the spacer, and the proximity of rDNA and heterochromatin in Drosophila, pyrimidine tract analysis gave no indication of relatedness between the spacer and satellite DNA sequences. Species of Drosophila closely related to D. virilis have rDNA spacers that are homologous with those in D. virilis to the extent that hybridization of a cloned spacer segment of D. virilis rDNA to various DNA is comparable with hybridization to homologous DNA, and distributions of restriction enzyme cleavage sites are very similar (but not identical) among spacers of the various species. There is spacer length heterogeneity in the rDNA of all species, and each species has a unique major rDNA spacer length. Judging from Southern blot hybridization, D. hydei rDNA spacers have 20--30% sequence homology with D. virilis rDNA spacers, and a repetitive component is similarly sensitive to Msp I and Fnu DII digestion. D. melanogaster rDNA spacers have little or no homology with counterparts in D. virilis rDNA, despite a similar content of 0.25 kb repetitive elements. In contrast, sequences in rDNA that encode 18S and 28S ribosomal RNA have been highly conserved during the divergence of Drosophila species; this is inferred from interspecific hybridizations involving ribosomal RNA and a comparison of distributions of restriction enzyme cleavage sites in rDNA. PMID- 6266781 TI - Toward a molecular paleontology of primate genomes. I. The HindIII and EcoRI dimer families of alphoid DNAs. AB - Families of related, but nonidentical repetitive DNA sequences, termed the alphoid DNAs, have been identified and characterized in representative species from seven major primate Families. The sequences appear as old as the primate Order itself: they are found in a prosimian (lemur), in a New World monkey, and in all Old World primates examined, including man. The alphoid DNAs are uniquely primate sequences and they may represent the most abundant repetitive DNAs in the primate genome. - A classification scheme for two major families of alphoid DNAs is proposed that is based upon restriction enzyme analysis and Southern blotting with radioactive probes prepared from component alpha DNA (Maio, 1971) and from the human EcoRI dimer sequences (Manuelidis, 1976). The family of alphoid DNAs that hybridizes readily with component alpha is termed the HindIII family of alphoid DNAs. This family shows an almost universal distribution among present day primates. The family of DNA sequences that hybridizes readily with the human EcoRI dimer probe is termed the EcoRI dimer family of alphoid DNAs. This family may be restricted to the great apes and man. The two probes permitted the discrimination of different, but related alphoid families in present-day primates. Multiple alphoid sequence families are found within the genomes of individual primates and the major primate taxa can be characterized by the representations of the various alphoid DNAs within their genomes. - An Appendix is presented (Brown et al., 1981) indicating that competition hybridization effects may influence the autoradiographic banding patterns, and hence, the interpretations of Southern filter-transfer hybridizations when dealing with related repetitive sequences such as the alphoid DNAs that are present in abundance in eukaryotic genomes. PMID- 6266784 TI - [Enteroviral myocarditis--with an analysis of 10 cases (author's transl)]. PMID- 6266782 TI - Toward a molecular paleontology of primate genomes. II. The KpnI families of alphoid DNAs. AB - KpnI restriction of anthropoid primate DNAs, from a New World monkey to man, releases a series of segments that are remarkable among all of the alphoid DNAs in the constancy of their relative amounts in the various primate genomes, in their long-range organization, and in their internal sequence structure. These segments are labeled the KpnI A, B, C and D segments. Cross-hybridization analysis by Southern filter-transfer hybridization indicates that the KpnI segments represent separate and distinct families of alphoid DNAs. These families are termed the KpnI A, B, C and D families of alphoid sequences, of which only the KpnI A and B families were studied in detail here. - Evidence is presented suggesting that the KpnI segments do not exist as long, tandemly repeated sequences in the primate genome: rather, they may occur interspersed among other, perhaps nonalphoid sequences. From the stained gel patterns and from Southern filter-transfer hybridization experiments, the KpnI families appear to be absent from the genomes of the two prosimians studied - the galago and the black lemur. The KpnI A and B families are found among all of the anthropoid primates, including the New World capuchin monkey. The KpnI C family was detected in the genomes of the Old World anthropoid primates whereas the KpnI D family was detected only among the great apes and man. - The results are in accord with the observation (Musich et al., 1980) that with the continued evolutionary development of the primate Order, there has been a parallel trend toward an increased number and variety of alphoid DNA sequences. The properties of the KpnI families suggest that these sequences, unique among the alphoid DNAs, have been conservatively maintained throughout primate phylogeny and that they are among the most ancient of all primate DNAs. PMID- 6266783 TI - Chromosomal locations of two DNA segments that flank ribosomal insertion-like sequences in Drosophila: flanking sequences are mobile elements. AB - We report the chromosomal locations of two repetitive DNA sequences that flank ribosomal insertion-like sequences in Drosophila melanogaster. The chromocentric region of D. melanogaster contains many copies of sequences that are homologous to type 1 ribosomal insertions. These insertion-like elements are interspersed with other DNA segments that we call flanking sequences. Two distinct flanking sequences derived from the same cloned DNA molecule pDmI 101, the HindIII fragments 101E and 101F, were studied. Whole genome Southern blots with DNA from the D. melanogaster stocks Oregon R (P2), gt-1, and gt-X11 showed complex restriction patterns that differed substantially between the three stocks. This and other data show that flanking sequences are members of diverged repetitive sequence families. In situ hybridization to salivary gland chromosomes of gt-1 and gt-X11 showed that both sequences are homologous to the chromocenter and to about 5 to 8 (101E) or 25 to 30(101F) euchromatic sites in each stock. Most, if not all, of these sites differed in gt-1 and gt-X11. Both 101E and 101F are homologous to he chromocenter and very few euchromatic bands in D. simulans, but 101F is homologous to numerous bands in D. mauritiana. We conclude that the flanking sequences represented by 101E and 101F are mobile elements within the genome of Drosophila. These two sequences differ in several structural features from mobile DNA elements previously described in this organism. PMID- 6266785 TI - Adhesion properties of Entamoeba histolytica. AB - Trophozoites of Entamoeba histolytica adhere to and phagocytize red blood cells and bacteria. Furthermore, in the initial step of the amoebic infectious process the parasite attaches to intestinal epithelial cells. A lectin (carbohydrate binding protein) which apparently has a role in the attachment of the parasite to host cells was found in trophozoites of E. histolytica. When amoeba cells were disrupted by freeze-thawing, the lectin activity, as determined by haemagglutination of human erythrocytes, remained associated with the sedimented membrane fraction. This activity was pH dependent and heat and oxidation sensitive, and was destroyed by proteolysis and on autoincubation. Moreover, the lectin activity was inhibited by a variety of N-acetylglucosamine-containing compounds such as chitin and chitin oligosaccharides, bacterial peptidoglycan, rabbit colonic mucus, bovine and human serum, an IgA fraction isolated from human colostrum, and IgG from sera of amoebiasis patients. These glycoconjugates also interfered with the adherence of intact radiolabelled amoeba trophozoites to human intestinal epithelial cells as well as their attachment to red blood cells. Although the lectin activity and the toxin-like activity previously found in E. histolytica seem to be two separate substances, they share a number of properties which suggest that they are related and may have a function in pathogenicity. PMID- 6266786 TI - [A morphological study of factors influencing postoperative survival of patients with hepatocellular carcinoma (author's transl)]. PMID- 6266787 TI - Flow cytometric determination of esterase and phosphatase activities and kinetics in hematopoietic cells with fluorogenic substrates. AB - Viable and formaldehyde fixed rat bone marrow or spleen cells and rat or human blood leukocytes were incubated with fluorescein (fluorescein-diacetate, dibutyrate and -laurate) or umbelliferone (4-methyl umbelliferyl acetate and phosphate) fluorogenic substrates for subsequent flow cytometric determination of cell fluorescence and cell volume. Formaldehyde-fixed cells preserved between 14 and 20% of the enzyme activity of the unfixed cells and the number of cell clusters for fixed and unfixed cells was the same. The esterase substrates revealed one cell cluster for spleen cells, two for bone marrow cells and four for peripheral blood leukocytes. Phosphatase activity was only associated with a cell cluster of large cells. The time course of substrate cleavage was linear during the first 10 min of incubation. Later on a plateau was reached. Specific enzyme activities were calculated on a single cell level from the simultaneous cell volume and cell fluorescence measurement. Two enzyme activities could be measured simultaneously by using a substrate mixture of umbelliferone acetate and fluorescein acetate. PMID- 6266788 TI - Prevalence of colonic diverticular disease in southern Iran. AB - Five hundred fifty-six barium enema examinations performed in male and female patients (aged 20--70+ years) were studied retrospectively to estimate the prevalence of colonic diverticulosis in southern Iran. The frequency of diverticulosis in all subjects above the age of 20 years was 1.6 per cent, in persons above the age of 50 years, 2.4 per cent, and in persons below the age of 50 years, 1.2 per cent. This is in marked contrast to the high prevalence of the disease in Western countries, e.g., the 20 per cent overall prevalence in the United States. The high dietary fiber intake of the Iranian people may explain the rarity of the disease in Iran. PMID- 6266790 TI - Decreased alpha-adrenergic receptors in newborn platelets: cause of abnormal response to epinephrine. AB - Platelets of newborn infants fail to aggregate or release adenosine diphosphate in response to epinephrine. Because epinephrine-induced aggregation is an alpha adrenergic event, we considered the possibility that newborn platelets possess fewer alpha-adrenergic receptors than do those of adults. Therefore we compared the specific binding of the alpha-adrenergic antagonist, [3H]-dihydroergocryptine (DHE), in intact washed platelets prepared from paired samples of maternal and cord platelet-rich plasma. Newborn platelets demonstrated normal kinetics of [3H] DHE binding and normal affinity for [3H]-DHE. Scatchard analysis of [3H]-DHE binding indicated a single class of binding sites that exhibited a high affinity for the radioligand (Kd = 10 nM). Maternal platelets were found to bind approximately 2-fold more [3H]-DHE than newborn platelets (3.70 +/- 0.28 vs. 1.74 +/- 0.17 fmol/10(7) platelets) at saturation. This corresponds to 223 +/- 17 vs. 105 +/- 11 binding sites per platelet (p less than 0.001). Repeat washing of newborn platelets did not yield increased [3H]-DHE binding suggesting the binding sites had not previously been masked by elevated circulating levels of catecholamines in venous cord blood. When control platelets were incubated with concentrations of [3H]-DHE that half-saturated the alpha-adrenergic receptors, diminution of platelet function comparable to that seen in newborn platelets was observed. Since maternal and newborn platelets are similar size, it appears that a deficiency of alpha-adrenergic receptors may account for the diminished response of newborn platelets to epinephrine. PMID- 6266789 TI - Isolated retained antrum diagnosis by gastrin challenge tests and radioscintillation scanning. PMID- 6266792 TI - The Krukenberg tumor. Appearance on ultrasonography and review of the literature. AB - The term Krukenberg tumor refers to metastatic disease to the ovary and more specifically those metastases containing mucin-secreting signet cells. When this definition is used most of these tumors arise in the gastrointestinal tract although the term Krukenberg tumor has also been used more loosely to describe metastatic disease to the ovary from other sites such as breast and genital tract. On ultrasound examination, the Krukenberg tumor has been described as a complex type of mass showing both solid and cystic characteristics. When a mass with these echographic characteristics is found on pelvic sonography it is important to consider this entity in the differential diagnosis. PMID- 6266791 TI - Autoradiographic localization of 3H-diprenorphine in the Syrian hamster. AB - An autoradiographic technique is reported for the in vivo localization in the Syrian hamster of small doses of the opiate antagonist, 3H-diprenorphine. The regional distribution in the hamster brain was similar to that reported in the rat. The adrenal medulla showed a high degree of localization providing supportive evidence for the presence of opiate receptors in the medulla and a possible paracrine function for opioid peptides in this site. Other peripheral sites showed selective uptake of 3H-diprenorphine which was not apparently related to the vascularity of the tissue. PMID- 6266794 TI - [Acetylcholine diffusion through neuronal membranes]. PMID- 6266793 TI - [Kininase isolation from the venom of spider Latrodectus tredecimguttatus]. PMID- 6266795 TI - [Microinjection of viruses into animal oocytes and embryos. Integration of avian sarcoma viral genome into Drosophila melanogaster DNA]. PMID- 6266796 TI - [Differences in the density of topological coils of DNA from malignantly transformed and normal cells of the Syrian hamster]. PMID- 6266798 TI - [Learning ability of white rats following immunization with a conjugate of the oligopeptide ACTH 4-10 with albumin; absence of immunotolerance to ACTH 4-10]. PMID- 6266797 TI - [Effect of troponin I on the Ca-binding properties of calmodulin and activation of cyclic nucleotide phosphodiesterase by Ca ions]. PMID- 6266799 TI - [Cessation of treatment in childhood acute lymphatic leukemia. Long-term observations after meningosis prevention with intrathecal gold colloid radioisotopes and methotrexate]. AB - Cytostatic long-term treatment for about 36 months was administered to 18 children with acute lymphatic leukaemia who were in long-term remission (43-98 months). Prophylaxis of meningosis involved intrathecal 198Au colloid and methotrexate. Seven recurrences occurred during the long-term remissions: the bone marrow was involved six times, leukaemic meningosis occurred once. Five out of seven recurrences occurred within one year of cessation of treatment. There were no complications induced by intrathecal radio-gold, such as the apathy syndrome or leukoencephalopathy. Intrathecal methotrexate led to side effects before administration of radio-gold: encephalopathy twice, paraplegia once. Symptoms regressed completely in two children, one child with encephalopathy continues to have symptoms. All three children were given 198Au colloid intrathecally thereafter which was tolerated very well. 198Au colloid represents an alternative for prophylaxis of meningosis with 60Co telecobalt irradiation in leukaemias and non-Hodgkin lymphomas in childhood. PMID- 6266801 TI - Klippel-Trenaunay--Weber syndrome. PMID- 6266800 TI - [Etoposide. A new highly effective cytostatic agent in anaplastic small-cell bronchial carcinoma, other solid tumors and hemoblastoses]. PMID- 6266802 TI - Malignant trophoblastic disease with special reference to pulmonary involvement in Ibadan. PMID- 6266803 TI - 3H-PGE1 binding and production of cAMP and testosterone by Leydig cells during adolescence in rats. AB - 3H-PGE1 binding capacity of Leydig cells isolated form the testes of rats aged 25 to 120 days was studied together with in vitro responsiveness of cAMP and testosterone synthesis to PGE1. It was demonstrated that the specific binding of 3H-PGE1 by rat Leydig cells increased with age up to the 50th day and then gradually decreased. The changes in binding capacity of 3H-PGE1 did not correlate with the responsiveness of Leydig cells to PGE1 in cAMP and testosterone production during postnatal development, though this stimulatory effect of PGE1 was significant during the whole period studied. Finally, in vivo administration of PGE1 increased the production of testosterone by testes and also the level of this hormone in blood. PMID- 6266804 TI - Effect of the structure-stabilizing agent glycerol on detergent-solubilized follicle-stimulating hormone receptors from calf testis. PMID- 6266805 TI - Evidence for noradrenergic mediation of opioid effects on luteinizing hormone secretion. PMID- 6266806 TI - Binding of high density lipoprotein to human fetal adrenal membrane fractions. PMID- 6266807 TI - Alpha-adrenergic stimulation by clonidine increases plasma concentrations of immunoreactive beta-endorphin in rats. AB - Peripheral administration of the alpha-adrenergic agonist clonidine (0.5 mg/kg, sc) evoked a 2- to 3-fold rise (0.22 +/- 0.03 to 0.59 +/- 0.05 ng/ml) in plasma levels of beta-endorphin-like immunoreactivity (beta-END-LI) 15-30 min later in intact, but not hypophysectomized, rats. This rise in plasma beta-END-LI, which was dose dependent up to 0.5 mg/kg clonidine, appeared to be mediated by activation of alpha-adrenergic receptors, since pretreatment with the alpha adrenergic antagonists yohimbine (1 mg/kg, ip), phentolamine (1, 3, or 10 mg/kg, kp), or phenoxybenzamine (2 and 10 mg/kg, ip) partially or fully blocked clonidine's effect. By contrast, the beta-adrenergic antagonist propranolol (1 and 5 mg/kg, ip) did not modify the clonidine-induced increased in plasma beta END-LI. Given alone, the adrenergic blocking drugs were generally without effect on plasma levels of beta-END-LI. Clonidine appeared to be acting on the brain (or pituitary), since the intracerebroventricular injection of phenoxybenzamine (20 microgram) blocked the drug-induced rise in plasma beta-END-LI. These data suggest an alpha-adrenergic mechanism influences the release of pituitary beta END in the rat. PMID- 6266808 TI - Corticotropin-releasing factors (CRF) secreted by the rat median eminence in vitro in the presence or absence of ascorbic acid: quantitative role of vasopressin and catecholamines. AB - Microdissected rat median eminences (wet weight, 110 micrograms) were electrically stimulated in vitro in the presence of bacitracin and bovine serum albumin. Incubation media collected at 20-min intervals, were assayed for corticotropin-releasing factor (CRF) with dispersed pituitary cells and for arginine vasopressin (AVP) by a specific RIA. CRF activity of the media or of synthetic AVP was plotted as function of AVP content. Dose (AVP)-response (CRF) curves for media were not significantly different from those of synthetic AVP. Extracts of incubated median eminences had 3 times more CRF activity then the AVP contained within these extracts, showing that CRF distinct from AVP ws contained within the median eminences but had not been released into or had been degraded within the media. In the presence of 1 mM ascorbic acid, AVP release was not significantly different from AVP release in the absence of ascorbic acid, but accounted for only 49-67% of released CRF activity, suggesting that a CRF distinct from AVP had been released into or protected within the medium. At an AVP level similar to that found in hypophysial portal plasma, the total CRF activity of median eminence media were not significantly different in the presence or absence of 0.13 microM haloperidol or 1.3 microM propranolol in ascorbic acid-rich media, but were 12-17% (P less than 0.05) lower in the presence of 0.35 microM phentolamine. The results indicate that CRFs, distinct from AVP, released from the median eminence in vitro can be detected only when ascorbic acid is present in the medium, and furthermore, that AVP and some alpha adrenergic agonist account for at least 61-84% of released CRF activity. PMID- 6266809 TI - Insulin-induced hypoglycemia in conscious dogs. I. Dose-related pituitary and adrenal responses. AB - We have measured changes in plasma glucose, ACTH, corticosteroids, and vasopressin and hematocrit after five doses of insulin in six conscious dogs. We found insulin dose-related changes for each of these responses (P less than 0.01, by two-way analysis of variance). The increases in plasma ACTH and hematocrit correlated to the decrease in plasma glucose; the increase in plasma vasopressin was more strongly correlated with the increases in plasma Na+ than with the decreases in plasma glucose. Each dog appeared to have a characteristic ACTH response curve; therefore, the relationship between plasma glucose and plasma ACTH responses varied among dogs, but was significant in five of six dogs studied. Maximal plasma corticosteroid responses occurred with submaximal plasma ACTH responses (200-600 pg/ml). A single dose of insulin produced reproducible changes in plasma ACTH when given to five dogs in three separate experiments over a 2- to 6-month period. In these experiments, the measurement of ACTH allowed us to distinguish three levels of response to insulin, whereas measurement of the corticosteroid response allowed us to distinguish only two levels of response. PMID- 6266810 TI - Xylazine-induced hyperglycemia in cattle: a possible involvement of alpha 2 adrenergic receptors regulating insulin release. AB - The mechanism by which xylazine raises plasma glucose but lowers insulin concentrations was examined in Holstein cows. Intravenous injection of xylazine (15-150 micrograms/kg) induced a dose-dependent hyperglycemia and hypoinsulinemia for 3-4 h. An alpha 2-adrenergic blocking agent, yohimbine, and an alpha 1- and alpha 2-adrenergic blocking agent, phentolamine, at 500 micrograms/kg each reduced or abolished xylazine-induced hyperglycemia and hypoinsulinemia. The alpha 1-adrenergic blocking agents, prazosin and phenoxybenzamine, at 500 micrograms/kg each did not exert such antagonism. Prazosin at the dose studied even prolonged xylazine-induced hypoinsulinemia. The alpha-adrenergic blocking agents alone at 500 micrograms/kg each did not change either plasma glucose or insulin concentrations. The present study suggests that xylazine-induced hyperglycemia and hypoinsulinemia are mediated by alpha 2-adrenergic receptors, possibly in beta-cells of pancreatic islets which inhibit the release of insulin. The present study further suggests the use of xylazine as a pharmacological tool in the study of adrenergic influence on in vivo insulin release. PMID- 6266811 TI - Obligatory role of luteinizing hormone (LH) in the initiation of preovulatory follicular growth in the pregnant rat: specific effects of human chorionic gonadotropin and follicle-stimulating of hormone on LH receptors and steroidogenesis in theca, granulosa, and luteal cells. PMID- 6266812 TI - Effect of insulin and glucagon on amino acid transport in isolated hepatocytes after partial hepatectomy in the rat. PMID- 6266813 TI - Delta 9-tetrahydrocannabinol suppression of prolactin secretion in the rat: lack of direct pituitary effect. AB - The effects of (--)trans-delta 9-tetrahydrocannabinol (THC) on tonic PRL secretion were investigated in long term ovariectomized or hypophysectomized/pituitary-autografted female rats and in flask incubations of anterior pituitary tissue. Intravenous injection of 0.25-8.0 mg THC/kg BW into ovariectomized rats markedly suppressed serum PRL 60 min later relative to control PRL levels. In a second experiment, ovariectomized rats bearing intraatrial cannulae were injected with 0.5 mg THC/kg BW, iv, and serial blood samples were drawn. PRL was significantly suppressed at 10 min, with persistence of the suppression for the duration of the 70-min sampling period in this time course study. In contrast, the administration of 1.0 mg THC/kg BW, iv, to hypophysectomized/pituitary-autografted female rats failed to influence PRL secretion throughout a 120-min posttreatment sampling period. The apparent inability of THC to directly suppress PRL release from pituitary tissue was further studied by in vitro flask incubations of anterior pituitary tissue. Although a 1-h exposure of rat anterior pituitary tissue to bromocryptine (CB 154; 2.2 X 10(-4) M) suppressed subsequent PRL release, similar exposure to 10( 6) or 10(-4) M THC had no influence. The failure of THC to alter tonic PRL secretion in hypophysectomized/pituitary-autografted rts or PRL release from pituitary tissue in vitro strongly suggests that the central nervous system rather than the pituitary is the site of THC action in the acute suppression of tonic PRL secretion. PMID- 6266814 TI - Follicular steroidogenesis and gonadotropin binding to ovine follicles during the estrous cycle. AB - The interrelationships among [125I]hCG binding in thecal and granulosa cells, antral fluid steroid concentrations, follicular size, and ovarian steroid secretion were examined at three different stages of the estrous cycle. Group 1 ewes were ovariectomized during the luteal phase of the estrous cycle, and the other groups were ovariectomized before (group 2), or after (group 3) the peak of the preovulatory LH surge. Times of luteolysis and the LH surge were assessed by measurement of peripheral concentrations of progesterone and LH. Three patterns of [125I]hCG binding to follicles were noted: 1) binding to both thecal and granulosa cells (activated follicle), 2) binding to the thecal cell layer only, and 3) no observed binding. In general, there was one active follicle per ewe, or one per ovary, and the number of active follicles was not different from the number of corpora lutea in each of the three groups. The active follicles were significantly larger than the other two classes of follicles. Antral fluid estradiol concentrations were significantly greater in the active follicles and were higher in group 2 ewes than in the other two groups. In group 2, antral fluid testosterone concentrations were significantly higher in follicles with LH receptors in the thecal cell layer only. Ovarian secretion of testosterone and estradiol increased during the early follicular phase (group 2), with the major secretion coming from the ovary containing the active follicle. Ovarian progesterone secretion was high in ovaries containing active corpora lutea which prevented the assessment of ovarian follicular secretion of progesterone. The follicle with LH receptors in thecal and granulosa cells was responsible for the increased estradiol secretion observed during the preovulatory period and is presumed to be the ovulatory follicle. PMID- 6266815 TI - Regulation of human chorionic gonadotropin synthesis in cultured human placental cells by glucocorticoids. AB - The synthesis of hCG and its subunits in temperature-sensitive, simian virus 40 tsA mutant-transformed human first trimester and term placental cells and in choriocarcinoma cells was studied in the presence and absence of glucocorticoid hormones. The tsA-transformed placental cells were studied at 33 C (the temperature at which the cells exhibit the transformed phenotype) and at 40 C (the temperature at which the cells regain their differentiated nontransformed phenotype). The glucocorticoids cortisol and dexamethasone did not affect the synthesis of hCG or hCG alpha in either transformed term placental cells or choriocarcinoma cells. In the tsA-transformed first trimester placental cells, however, glucocorticoids greatly inhibited hCG synthesis but induced hCG alpha synthesis. The inhibition on hCG synthesis was immediate, stronger at 40 C than at 33 C, and independent of the growth stage of the cells. The glucocorticoid effects were specific; neither estradiol nor progesterone affected the synthesis of hCG or hCG alpha. Furthermore, progesterone did not block the action of the glucocorticoid. These selective effects in cultured first trimester placental cells suggest that glucocorticoids may play an important role in the regulation of hCG production during early pregnancy. PMID- 6266816 TI - Solubilization and molecular weight estimation of prolactin receptors from Rana catesbeiana tadpole liver and tail fin. PMID- 6266817 TI - The arterio-venous difference for immunoreactive parathyroid hormone and the production of adenosine 3,'5'-monophosphate by isolated perfused bone: studies with analogs of parathyroid hormone. AB - Recent studies suggest that the uptake of immunoreactive parathyroid hormone (iPTH) displays different characteristics in liver, kidney, and bone. Using the isolated perfused canine bone, we have characterized the uptake of two synthetic analogs of PTH, bovine PTH-(3-34) [bPTH-3(3-34)] and [Nle8,Nle18,Tyr34]bPTH-(3 34) amide, which had previously been shown to inhibit PTH-stimulated adenylate cyclase activity in renal membranes. During the infusion of synthetic bPTH-(1-34) (3 ng/ml), extraction of iPTH by isolated perfused bone averaged 37 +/- 1%, and cAMP production rose from 6.2 +/- 2.0 to 21 +/- 3 pmol/min. Extraction of bPTH-(3 34) was similar (35 +/- 2%), but cAMP levels did not increase over baseline with PTH concentrations as high as 100 ng/ml. Simultaneous infusion of bPTH-(1-34) and bPTH-(3-34) at molar ratios of 1:2 led to a 50% inhibition of PTH-stimulated cAMP increases. The extraction by bone of the more potent in vitro inhibitor of renal cortical adenylate cyclase [Nle8,Nle18,Tyr34]bPTH-(3-34) NH2 (3 ng/ml) averaged 39 +/- 2%. In contrast, cAMP production rose from a baseline of 5.6 +/- 0.5 to 12.5 +/- 2.0 pmol/min, demonstrating agonist activity for the analog. These studies show that [Nle3,Nle18,Tyr34]bPTH-(3-34) NH2 has agonist properties in isolated perfused bone, and unsubstituted bPTh-(3-34) inhibits PTH-stimulated cAMP release by perfused bone. PMID- 6266818 TI - Alterations of brain cerebral cortex CCK receptors in the ob/ob mouse. AB - We investigated the binding of CCK to its receptors in the brain and pancreas of the ob/ob mouse, an animal model of inherited obesity. The binding of CCK to its receptors in the cerebral cortex was increased, and Scatchard analyses revealed that this increased binding was due to an increase in the number of receptor sites. By contrast, there was no increased binding to CCK receptors in other brain regions, including the hypothalamus, or to CCK receptors in the pancreas. In the db/db mouse, another animal model of inherited obesity, no changes in CCK binding to its receptors in cerebral cortex and other brain regions were detected. Our study demonstrates, therefore, that the ob/ob mouse has changes in brain CCK receptors and suggests that certain types of obesity in mice could be related to altered CCK binding and action. PMID- 6266819 TI - A case of insulin autoimmune syndrome associated with small insulinomas and rheumatoid arthritis. AB - Twenty five cases of insulin autoimmune syndrome including this case has been reported so far without having the pathogenesis clarified. This paper describes a case which suggests one aspect of pathogenesis. The patient, a housewife concurrently had insulinoma and severe rheumatoid arthritis, complaining of hypoglycemic syncope attacks. During the attacks her blood sugar levels ranged from 19 to 22 mg%. Her serum extractable immunoreactive insulin (IRI) and insulin binding antibody levels were 557 microunits/ml and 0.390 mU/ml, respectively. gamma-Globulin-bound insulin was also measured electrophoretically. Bio-Gel P 10 column chromatography eluted almost all IRI at the void volume at pH 7.4 and a smaller but significant IRI peak also at pH 3.0. Selective angiography revealed a tumor-like staining in the pancreas body. Pancreatectomy relieved her of hypoglycemic attacks. Histology disclosed two small insulinomas. Insulinoma, rheumatoid arthritis and insulin autoimmune syndrome coexisted in this case, suggesting some causal relationship among them. PMID- 6266820 TI - Effect of propranolol on glucose-induced insulin response in rats with insulinomas. AB - This paper describes an inhibitory effect of propranolol on insulin secretion in rats with pancreatic islet cell tumors which have been induced by streptozotocin (65 mg/kg body weight) and nicotinamide (500 mg/kg). Following glucose ingestion (3 g/kg), propranolol (4 mg/kg) was injected into the tumor-bearing rats. Plasma insulin decreased paradoxically despite an increase in blood glucoses. In contrast, propranolol did not suppress insulin secretion in normal rats. The drug was found to have no effect on glucagon secretion in either experimental or control animals during glucose load. This may suggest that the experimentally induced insulinoma in hypersensitive to propranolol for inhibiting insulin secretion. PMID- 6266821 TI - Influence of ACTH secreting tumor (MtTF4) on fetal rat adrenal gland steroidogenesis in vitro in prolonged pregnancy. AB - Pregnant female rats with ACTH secreting tumor (MtTF4) have prolonged pregnancy and cannot deliver. The fetuses of tumor bearing females have in prolonged pregnancy on days 24 and 25 of pregnancy greater body weight and smaller adrenal weight as compared to intact fetuses of the 22nd day of pregnancy. The fetal adrenal glands converted to vitro 4-14C progesterone to radioactive 11 deoxycorticosterone (DOC), corticosterone (B), 18-hydroxy-11-deoxycorticosterone (18-OH-DOC), 18-hydroxy-corticosterone (18-OH-B) and aldosterone. Fetal adrenal glands in prolonged pregnancy synthetized in vitro less amount of radioactive DOC, B and 18-OH-DOC. A negative relationship exists between the maternal corticosterone which passes the placenta to fetuses and corticosteroidogenesis of fetal adrenal glands. These results indicate the possibility that fetal rat adrenal glands with their corticosteroids participate in pregnancy and influence normal delivery. PMID- 6266822 TI - The short-term effect of cortisol, dexamethasone and ACTH administration on the serum levels of hexuronic acids and monosaccharides in man. AB - The levels of serum monosaccharides (SMO) and hexuronic acids (SHA) were measured in subjects without any metabolic or endocrine disease after a short-time administration of cortisol, dexamethasone and ACTH. The effects of the three hormones were evaluated in regard to the urinary excretion of free cortisol and cortisone at basal conditions. In thirteen subjects a significant increase of SMO during cortisol treatment was registered after 24 hours. A distinct difference in the response of SMO to cortisol treatment was observed in patients with normal or increased cortisol excretion, respectively. In the subjects with high urinary free corticoids a peak of SMO occurred soon after 4 hours after cortisol administration, in the next 48 hours no tendency of return towards basal levels was observed. In the subjects with normal urinary free cortisol excretion only a slight increment was seen after 24 hours. Soon after 4 hours in eight subjects dexamethasone administration resulted in an increase of SMO without regard to the excretion of urinary free corticoids. The highest values were obtained after 28 hours of dexamethasone treatment. Ten hours after cessation of dexamethasone the levels of SMO reached the basal values. In the study in which ACTH was administered, an increment of SMO was registered only in the first four hours. In the group of subjects treated with ACTH a slight difference between subjects with normal and increased corticoid excretion was seen. The levels of SHA successively increased after the administration of all three hormones, without regard to the basal excretion of urinary free corticoids. This increase persisted also 10 hours after cessation of cortisol and dexamethasone, and 40 hours after the last dosis of ACTH, respectively. The possibility of an altered metabolism of glucose through the glucuronate pathway under conditions of glucocorticoid excess is discussed. PMID- 6266823 TI - Adverse effects of phenytoin on peripheral nerves and neuromuscular junction: a review. AB - Review of the literature shows that long-term phenytoin therapy is associated with peripheral neuropathy and neuromuscular disorder that rarely can be symptomatic. The usual manifestations of the peripheral neuropathy are lower extremity areflexia, sensory deficits, and reduced conduction velocities. The risk for these peripheral nerve abnormalities is greater with increased serum levels or long duration of therapy (usually more than 5 years). The relative risks according to age groups or number and kinds of antiepileptic drugs used are undetermined. It is not known if detected abnormalities are static or slowly progressive. Isolated case reports have claimed the resolution of signs and symptoms after discontinuance of therapy or correction of a state of intoxication. Appropriate measures to prevent the appearance or progression of the complications are discussed in light of the available evidence. PMID- 6266824 TI - Herpes virus inactivation by chemical carcinogens: differential inactivation of herpes simplex viruses by 4-nitroquinoline 1-oxide and related compounds. AB - Treatment of stocks of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) with the chemical carcinogen 4-nitroquinoline 1-oxide (NQO) resulted in inactivation of virus infectivity at rates which were directly dependent on the concentration of NQO and interval of exposure to NQO. HSV-1 strains were more sensitive than HSV-2 strains to inactivation by NQO, although survival curves of both HSV types were multicomponent. Exposure of HSV-2 to a related group of chemicals suggested that the structural specificity required for inactivation of this virus was similar to that established by previous in vivo carcinogenicity tests. PMID- 6266825 TI - The occurrence of brown adipose tissue in outdoor workers. AB - Histochemical reactions and activities of mitochondrial enzymes in adipose tissue around the neck arteries and in pericardium were studied in men who had been outdoor workers in northern Finland. The purpose was to study the occurrence of brown fat in workers having been exposed to cool or cold ambient temperature. Indoor workers of the same age were used as controls. Histochemically, no mitochondrial enzyme reactions were seen in the adipose tissues taken from the indoor workers, whereas some outdoor workers had some multilocular adipose tissue, mostly around the neck arteries. Biochemical parameters also showed increased enzyme activities of aerobic energy metabolism in the adipose tissue of these people. The present results suggest that working in the cold can retain brown adipose tissue in "strategic" places in human adults. PMID- 6266826 TI - Purification and properties of two 2-oxoacid:ferredoxin oxidoreductases from Halobacterium halobium. AB - Pyruvate:ferredoxin oxidoreductase and 2-oxoglutarate:ferredoxin oxidoreductase were obtained from cell-free extracts of Halobacterium halobium as homogeneous proteins after ammonium sulfate precipitation, salting-out chromatography with ammonium sulfate on unsubstituted agarose, gel filtration and chromatography on hydroxyapatite. The respective molecular weights are 256000 and 248000. Both enzymes consist of two sets of non-identical subunits of Mr 86000 and 42000 in the case of the pyruvate-degrading enzyme and of 88000 and 36000 in the case of the 20 -oxogluatarate-degrading enzyme. Analyses indicate that an intact enzyme molecule contains two [4 Fe-4S]2 + (2 + , 1+) clusters and two molecules of thiamin diphosphate. Flavin nucleotides, lipoic acid and pantetheine are absent. Thus the enzymes are very similar to the 2-oxoacid:ferredoxin oxidoreductases from fermentative and photosynthetic anaerobes described previously, but are clearly different from the 2-oxoacid dehydrogenase multienzyme complexes which commonly occur in anaerobic organisms. PMID- 6266827 TI - The catalytic mechanism of 2-oxoacid:ferredoxin oxidoreductases from Halobacterium halobium. One-electron transfer at two distinct steps of the catalytic cycle. AB - The catalytic cycle of the 2-oxoacid:ferredoxin oxidoreductases from Halobacterium halobium was investigated. The first step is binding of the 2 oxoacid to the enzyme followed by decarboxylation and transfer of one electron to the [4Fe-4S] cluster of the functional unit. The cluster is then reoxidized by ferredoxin or, in the absence of the physiological electron acceptor, by oxygen. In the resulting stable enzyme-intermediate radical the decarboxylation product of the 2-oxoacid remains tightly bound until reaction with coenzyme A caused formation of acyl-CoA and concomitant transfer of the second electron to the cluster, which again is reoxidized by ferredoxin or oxygen. After purification, part of the enzyme molecules still contain the intermediate radical. Enzyme preparations either free of radical or containing enhanced amounts are obtained by treatment with coenzyme A or 2-oxoacid, respectively. Whenever the radical is present in an enzyme molecule the respective binding site for the 2-oxoacid is blocked. PMID- 6266828 TI - The energy-linked transhydrogenase in rat liver in relation to the reductive carboxylation of 2-oxoglutarate. PMID- 6266829 TI - The primary structure of Escherichia coli RNA polymerase. Nucleotide sequence of the rpoB gene and amino-acid sequence of the beta-subunit. AB - The combined structural study of proteins and of their corresponding genes utilizing the methods of both protein and nucleotide chemistry greatly accelerates and considerably simplifies both the nucleotide and protein structure determination and, in particular, enhances the reliability of the analysis. This approach has been successfully applied in the primary structure determination of the beta and beta' subunits of Escherichia coli DNA-dependent RNA polymerase and of their structural genes, yielding a continuous nucleotide sequence (4714 base pairs) that embraces the entire rpoB gene, the initial part of the rpoC gene and the intercistronic region, together with the total amino acid sequence of the beta subunit, comprising 1342 residues, and the N-terminal sequence of the beta' subunit (176 residues). PMID- 6266830 TI - Brain enzymes and ischemia. AB - Changes in the maximal rate of some cerebral enzymatic activities related to 400ene transduction and neurotransmission (lactate dehydrogenase; citrate synthase and malate dehydrogenase; total NADH-cytochrome c reductase and cytochrome oxidase; glutamate dehydrogenase; acetylcholine esterase) were assayed both in the crude or purified mitochondrial fraction and in the crude synaptosomal fraction from rat whole brain or cerebral cortex. The evaluations were performed in rats before and after a postdecapitative normothermic ischemia of 5, 10, 20 and 40 min duration. Modification observed in some of these activities wer discussed for comparison with other experimental results from different researchers. At present no definite conclusions can be drawn, but certainly the observed modifications in activity of enzymes are not passive but expression of deranged metabolism of ischemic neurons. PMID- 6266832 TI - Enzymoimmunoassay of the main core protein (p28) of mouse mammary tumour virus (MMTV). PMID- 6266831 TI - Heterotransplantation of natural bovine lymphosarcoma to nude mice. PMID- 6266834 TI - Fc and C3 receptor patterns on two EBV- negative Burkitt lymphoma lines during acute exposure to EBV (P3HR-1 substrain). PMID- 6266833 TI - The apparent lack of association of antibody activity to murine leukemia virus and lymphoma development in (AKR x CBA) F1 mice. PMID- 6266835 TI - Histologic subtypes of small cell carcinoma of the lung: response to therapy. PMID- 6266836 TI - Codeine-induced memory changes: nature and relationship to opiate system. AB - Learning and recall processes were studied in three experiments with 33 subjects, 1 and 3 h after oral administration of codeine phosphate 25 mg, 50 mg and 100 mg. Recall was measured 3 and 24 h after drug administration. Nine subjects received naloxone i.m. with the 50 mg dose of codeine. Learning and memory were assessed by using associative, serial and concept learning tasks. Flicker fusion frequency was measured to assess the general vigilance level of the subjects. Learning performance in the serial learning task was improved 3 h after administration of codeine 100 mg. Recall in the serial learning task was also improved after codeine 25 mg, but only when the material was learnt after 1 hour and was recalled 24 h after drug intake. To demonstrate the enhanced recall both learning and recall had to take place under the same drug condition. The same test showed a tendency to enhanced recall after codeine 50 mg of material learnt 1 hour after drug intake and recalled 24 h later. This effect was counteracted by naloxone. The data are consistent with the hypothesis that codeine may exert its action via opiate receptors and that this system participates in memory functions. PMID- 6266837 TI - Cross-reactive anti-vesicular stomatitis virus (VSV) cytotoxic T lymphocytes recognize the major surface glycoprotein. AB - The major surface glycoprotein (G) of vesicular stomatitis virus (VSV) was purified and incorporated into lipid vesicles containing the purified hemagglutinin-neuraminidase (HN) and fusion (F) glycoproteins of Sendai Virus. These lipid vesicles were then used to modify the render target cells susceptible to lysis by anti-VSV cytotoxic T lymphocytes. The results obtained provide direct evidence that the G protein is a target antigen for specific and cross-reactive anti-VSV cytotoxic T lymphocytes. The significance of this work is discussed. PMID- 6266838 TI - Activation of T lymphocytes by lectins and carbohydrate-oxidizing reagents viewed as an immunological recognition of cell-surface modifications seen in the context of "self" major histocompatibility complex antigens. PMID- 6266839 TI - GABA and baclofen potentiate the K+-evoked release of methionine-enkephalin from rat striatal slices. AB - GABA potentiates the potassium-evoked release of methionine-enkephalin (ME) from slices of rat corpus striatum. This potentiation is observed only when a submaximal concentration (30 mM) of K+ is used to evoke release. The effect of GABA is dose-dependent between 100 and 100 micrometers. The basal release of ME is not altered by these concentrations of GABA. Before, but not muscimol, mimics the effect of GABA on the evoked release of ME. This effect is not stereoselective as both the (+)- and (-)-isomers of baclofen enhance ME release. Picrotoxin (100 micrometers) blocks the enhancement of ME release produced by both GABA and baclofen. Bicuculline methiodide (100 micrometers) does not block the effect of GABA. The effect of GABA on ME release may be mediated by an atypical GABA receptor which is activated by baclofen. PMID- 6266840 TI - Relationship between contraction and cyclic GMP levels of guinea pig taenia coli. AB - The relationship between isometric tension and the increase in cyclic GMP level associated with the initial phase of drug-induced contraction of taenia coli was studied. Maximal contraction induced by 100 micrometers carbachol or 124 mM KCl occurred in 30 sec and was associated with an increase in cyclic GMP levels of at least ten fold. However, 100 micrometers serotonin or low concentrations of carbachol (30 microM) produced nearly maximal contraction but only 10--20% of the maximal elevation in cyclic GMP induced by high concentrations of KCl. Furthermore, in the presence of a low concentration of Ca2+, or verapamil, both 124 mM KCl and 100 micrometers carbachol increased cyclic GMP with little elevation in isometric tension. Thus, large contractions were obtained with only small increases in cyclic GMP, and under other conditions, large increases in cyclic GMP were obtained with little increase in isometric tension. The results suggest that the initial increase in cyclic GMP level caused by these agents is not directly dependent on Ca2+ in the cellular pool containing the contractile proteins. PMID- 6266841 TI - Interaction of catecholamines and ethanol on the kinetics of rat brain (Na+ + K+) ATPase. AB - The effects of catecholamines (CA) and ethanol (EtOH), singly and in combination, on the kinetics of rat brain (Na+ + K+)-ATPase were studied. Addition of 0.05 M EtOH alone did not change Vmax or Km for K+, Na+, Mg2+ and ATP. Addition of 0.1 mM dopamine (DA) or noradrenaline (NA) alone stimulated the enzyme activity in presence of vanadium-containing ATP as substrate, but not with vanadium-free ATP except in the presence of high Mg2+ : ATP ratios. CA alone decreased the Km slightly for K+ and by about 50% for ATP, increased it for Mg2+ and did not change it for Na+. However, the combination of DA or NA + EtOH produced a marked inhibition which was competitive for K+, and uncompetitive or mixed for Mg2+, Na+ and ATP. The inhibitory effect of NA + EtOH was abolished in 20 mM K+. These findings suggest that NA sensitizes the enzyme to EtOH inhibition at physiological K+ concentrations, by conformational change away from the outwardly facing K+-binding E2P for to the inwardly facing Na+-binding E1P form. PMID- 6266842 TI - Diphenylhydantoin-induced block of the rat phrenic nerve-diaphragm preparation pretreated with p-hydroxymercuribenzoate. AB - Pretreatment of the rat phrenic nerve-diaphragm preparation with the sulfhydryl (SH) blocking agent p-hydroxymercuribenzoate (pOHMB) increased the blocking efficiency of the antiepileptic drug diphenylhydantoin (DPH) during indirect stimulation. Another SH-blocking agent, N-ethyl-maleimide (NEM) did not potentiate the block, but SH-group protection with dithiothreitol (DTT) abolished the effect of pOHMB. SH-binding was thus necessary but not sufficient for enhancement of DPH-block. High Ca2+-concentration potentiated the block. Well maintained response of the isolated phrenic nerve, and of the diaphragm during direct stimulation, located the block at the neuromuscular junction. Microelectrode records in preparations which were curarized, cut or Mg2+ paralyzed to abolish action potential activity, disclosed an abrupt cessation of end-plate potentials (EPPs) by DPH, and pOHMB pretreatment reduced the time period to abrupt EPP fallout in the curarized preparation, suggesting depressed nerve terminal excitability as the cause of the block and its potentiation. Observation of miniature EPPs beyond the time of EPP cessation excluded a postsynaptic block. The pOHMB-treated preparation is suggested as a model for testing antiepileptic drugs. PMID- 6266843 TI - 3-O-,4-O-diacetylisoproterenol and 3-O-,4-O-dibenzoylisoproterenol: hypothermic effects in mice and the involvement of beta-adrenergic receptors. AB - Prodrugs of isoproterenol, 3-O-,4-O-diacetylisoproterenol (DAI) and 3-O-,4-O dibenzoylisoproterenol (DBI), were tested for effects on colonic temperature in mice. Intraperitoneal injections of DAI or DBI (20, 50 and 125 mumol/kg) produced a dose-related hypothermia. Isoproterenol (125 mumol/kg) and its metabolite, 3-O methylisoproterenol (125 mumol/kg), caused hypothermia of a lesser intensity. The involvement of beta-adrenergic receptors in the hypothermic effect of DAI (50 mumol/kg) was established by pretreatments with propranolol and sotalol. The results are discussed in terms of the pharmacodynamics of prodrugs, the pharmacokinetics and mechanism of action of isoproterenol, and the possible role of beta-receptors in temperature regulation. DAI and DBI may be useful as prodrugs for the activation of central beta-receptors. PMID- 6266844 TI - Antagonism by chlornaltrexamine of some effects of delta 9-tetrahydrocannabinol in rats. AB - Chlornaltrexamine (beta-CNA) a selective, long-acting irreversible opiate antagonist inhibited the analgesia, hypothermia, hypothermia tolerance and physical dependence produced by delta 9-tetrahydrocannabinol (THC) in rats. The results suggest that there are some common features between cannabis and opiates and some actions of THC may be mediated by opioid related mechanisms in the central nervous system. PMID- 6266845 TI - Levonantradol, a potent cannabinoid-related analgesic, antagonizes haloperidol induced activation of striatal dopamine synthesis. AB - Levonantradol antagonized the compensatory acceleration of striatal dopamine synthesis induced by haloperidol. This effect was stereospecific, since the pharmacologically less active enantiomer, dextronantradol was approximately 30 times less effective. delta 9-Tetrahydrocannabinol at a dose 320 times higher than levonantradol also attenuated the haloperidol effect, but cannabidiol was inactive at a dose 750 times higher. GABA-like actions of levonantradol may be responsible for this responsible for this antagonism of haloperidol, but anticholinergic effects may also contribute. PMID- 6266846 TI - Benzodiazepine receptor increase following repeated pentylenetetrazole injections. PMID- 6266848 TI - Comparative effects of alpha-methyldopa, propranolol and hydralazine therapy on cardiac adenylate cyclase activity in normal and spontaneously hypertensive rats. AB - Normotensive (WKY) and spontaneously hypertensive (SHR) male rats were treated orally, one week after weaning and for 9 weeks, with alpha-methyldopa (100 mg/kg per day), propranolol (30 mg/kg per day) or hydralazine (10 mg/kg per day). Untreated WKY and SHR rats served as controls. The development of hypertension in SHR rats were attenuated by treatment but none of the drugs was able to restore the impairment in isoproterenol, secretin and glucagon responsiveness of cardiac adenylate cyclase activity which is characteristic of these animals. In heart membranes from both WKY and SHR rats, alpha-methyldopa treatment increased the number of beta-adrenoceptors by 20-32% and the maximal response of adenylate cyclase activity to isoproterenol and glucagon by 20-34%. By contrast, the beta blocker propranolol was ineffective on these parameters. The results obtained are consistent with the hypothesis that the change in adenylate cyclase seen in SHR rats is genetic in origin and is not a consequence of hypertension. PMID- 6266847 TI - Interaction of anticonvulsants with the barbiturate-benzodiazepine-GABA receptor complex. AB - Unlike the anesthetic barbiturate pentobarbital and the anxiolytic pyrazolopyridine etazolate, which enhance [3H]diazepam binding to rat brain membranes, the anticonvulsant barbiturates phenobarbital and metharbital, and also chlormethiazole, at therapeutic concentrations (10-1000 muM), do not stimulate [3H]diazepam binding, but instead block the enhancement by both pentobarbital and etazolate. The same anticonvulsants at similar concentrations inhibit [3H]alpha-dihydropicrotoxinin (DHP) binding suggesting that these anticonvulsants compete for the same receptor sites as pentobarbital and etazolate, designated the barbiturate-picrotoxinin receptor component of the benzodiazepine-GABA receptor complex. PMID- 6266851 TI - Spontaneous nephroblastoma in Sprague-Dawley rats. AB - Pathological findings were described on nephroblastomas occurrred spontaneously in 3 young Sprague-Dawley rats. One side of kidneys was affected in each animal. Microscopically, the tumors consisted of epithelial elements showing undifferentiated to well-differentiated tubular arrangements, sometimes with glomeruloid and glomerular structures. A metastatic tumor nodule was found in the lung of one rat. PMID- 6266850 TI - Epinephrine as a potent releaser of immunoreactive beta-endorphin in rats. AB - The intravenous infusion of catecholamines to rats induced a dose dependent increase of immunoreactive beta-endorphin (beta-Endi) in plasma. The ED50 values of 1-epinephrine and 1-isoproterenol were 110 and 100 ng/kg X min respectively. 1 Propranolol, but not d-propranolol prevented the effect of 1-epinephrine. Infusion of 100 ng/kg X min of 1-epinephrine increased plasma epinephrine to 11 pmol/ml, a concentration that can occur during stress. We conclude that circulating catecholamines can stimulate beta-Endi secretion via a beta adrenergic receptor mechanism and may play a role in the response of beta-Endi to stress. PMID- 6266849 TI - Lack of modulation by presynaptic alpha 2-adrenoceptors of adrenergic transmitters release evoked by activation of 5-hydroxytryptamine and nicotine receptors. AB - Clonidine (4.3 X 10(-6) M) and yohimbine (2.8 X 10(-6) M) have been used to stimulate and to block alpha 2-adrenoceptors in the isolated perfused rabbit heart. Transmitter release from the terminal sympathetic fibres as a result of stimulation of the nerves leaving the stellate ganglion (SNS; 0.32-10 Hz) and bolus injections of 5-hydroxytryptamine (5-HT; 2.8-182 nmol) or dimethylphenylpiperazinium (DMPP; 26-418 nmol) was estimated from changes in the chronotropic response of the heart under conditions of constant end organ sensitivity to injected noradrenaline (0.06-15.1 nmol). In accordance with the literature, clinidine inhibited responses to SNS and was more effective against low than against high frequencies of stimulation; similarly, yohimbine enhanced responses to SNS. In contrast, neither clonidine no yohimbine had any effect on the indirect sympathomimetic response to 5-HT. Similarly yohimbine did not alter responses to DMPP. Clonidine produced inconsistent effects on the response to DMPP; the response to 105 nmol was unchanged whereas the response to 209 nmol was reduced. The results suggest that transmitter release from the cardiac sympathetic nerves of the rabbit heart evoked by 5-HT or DMPP is not subject to control through activation of alpha 2-adrenoceptors by the released transmitter. They lend support to the suggestion of Stjarne that alpha 2-adrenoceptor inhibition of transmitter release arises primarily from the suppression of impulse transmission from varicosity to varicosity within the adrenergic ground plexus rather than interference with a Ca2+-dependent step in excitation secretion coupling. PMID- 6266852 TI - Separation and concentration of murine hematopoietic stem cells (CFUS) using a combination of density gradient sedimentation and counterflow centrifugal elutriation. AB - To obtain concentrated suspensions of pluripotent hematopoietic stem cells *CFUS) from murine bone marrow, density gradient centrifugal sedimentation (DGCS) was combined with counterflow centrifugal elutriation (CE). This combination provided a 7.6 fold enrichment of the CFUS concentration. For DGCS, Percoll a suspension of silica particles coated with polyvinylpyrrolidone was used. For fractionation by the CE an elutriator rotor (JE-6, Beckman) was used for further concentration of the cells harvested from the DGCS. Bone marrow erythropoiesis was suppressed by transfusion plethora initiated 5-6 days before the bone marrow was harvested. These two physical separation procedures combined with transfusion plethora to suppress erythropoiesis are effective in producing an enriched fraction of CFUS without change in distribution of the histologic type of colonies. PMID- 6266853 TI - Characterization of multiple erythroid progenitors available in large quantity from rabbit marrow. AB - We have examined the characteristics of erythroid progenitors from rabbit marrow and assessed the potential of this species as a source from which substantial quantities of erythroid progenitors could be obtained. Plasma clot cultures of rabbit marrow demonstrate colonies consistent with erythroid colony forming units (CFUE) by day 2 and colonies resulting from two types of burst forming units (BFUE) seen on days 3 and 8-9, respectively. Characteristic colony morphologies were noted from each cell type as well as differential sensitivity to erythropoietin (Ep) with discrete maximum responses for each progenitor. Distinct buoyant density characteristics were noted when the precursors were subjected to isopyknic separation on linear density gradients of polyvinylpyrrolidone-coated silica. The total nucleated marrow cells obtained from each animal ranged from 1.7-4.7 X 10(9). The average yields for each progenitor wee 1.71(+/-0.43) X 10(7) for CFUE, 1.99(+/-0.36) X 10(6) for 3 day BFUE and 1.24(+/-0.11) X 10(6) for 8-9 day BFUE. PMID- 6266855 TI - Arborization of axons in oculomotor nucleus identified by vestibular stimulation and intra-axonal injection of horseradish peroxidase. AB - Axons in the medial rectus (MR) subdivisions of the oculomotor nucleus were identified by horizontal rotation and by electrical stimulation of the vestibular nerves and abducens nuclei. Three types of axons (vestibular type I and II and abducens interneurons) were then injected intra-axonally with horseradish peroxidase (HRP). Each injected axon was reconstructed under the microscope in the frontal and horizontal planes and terminal arborization and boutons contacting with MR motoneurons were studied. The MR motoneurons were identified by retrograde uptake of HRP, HRP being injected in the MR muscle prior to the intra-axonal experiment. The main types of horizontal canal-related axons were as follows: (1) ATD-unilateral termination axons: Most type I axons were of this type. Axons ascended in ascending tract of Deiters (ATD) to the oculomotor nucleus and terminated in ipsilateral MR area. (2) ATD-bilateral termination axons: Very few secondary canal responsive axons were in this group. Axon ascended in ATD to the oculomotor nucleus and terminated in MR motoneuron areas bilaterally and in Edinger-Westphal nucleus. (3) MLF-bilateral termination axons: Most type II neurons were in this group. Axons went up in the contralateral MLF and into both oculomotor nuclei. Their branches distributed to several motoneuron areas but only infrequently to the MR area; and to the Edinger-Westphal nucleus. (4) AB interneuron axons: Axons ascended in the MLF contralateral to cells of origin and terminated in the contralateral MR motoneuron area. PMID- 6266854 TI - Selective effects of (-)-baclofen on spinal synaptic transmission in the cat. AB - When ejected microelectrophoretically near spinal interneurones of cats anaesthetised with pentobarbitone and under conditions where postsynaptic excitability was maintained artificially at a constant level, (-), but not (+), baclofen selectively reduced monosynaptic excitation by impulses in low threshold muscle (Ia and Ib) and cutaneous (Aalpha) afferents. Polysynaptic excitation of interneurones and Renshaw cells by impulses in higher threshold afferents was less affected, and baclofen had little or no effect on the cholinergic monosynaptic excitation of Renshaw cells. Glycinergic and gabergic inhibitions of spinal neurones were relatively insensitive to baclofen. These stereospecific actions of baclofen, produced by either a reduction in the release of excitatory transmitter or postsynaptic antagonism, suggest that Ia, Ib, and Aalpha afferents may release the same excitatory transmitter which differs from that of spinal excitatory interneurones. Microelectrophoretic (-), but not (+), -baclofen also reduced primary afferent depolarization of ventral horn Ia extensor afferent terminations produced by impulses in low threshold flexor afferents, without altering either the electrical excitability of the terminations or their depolarization by electrophoretic GABA or L-glutamate. This stereospecific action of baclofen is interpreted as a reduction in the release of GABA at depolarizing axo-axonic synapses on Ia terminals. PMID- 6266856 TI - Visual-vestibular interaction in the flocculus of the alert monkey. I. Input activity. AB - Neuronal activity in the flocculus of alert Rhesus monkeys was recorded during vestibular stimulation (rotation of the monkey about a vertical axis in complete darkness), optokinetic stimulation (rotation of the visual surround around the stationary monkey), combined visual-vestibular stimulation (rotation of the monkey inside the stationary surround in light), and conflicting visual vestibular stimulation (rotation of the monkey together with the visual surround in the same direction). The input to the flocculus was recorded as non-Purkinje cell (non-P-cell) activity. Ninety per cent of the non-P-cells which were modulated during our stimulation paradigms carry information similar to that in the neurons of vestibular nuclei. This suggests that the main mossy fiber input to the flocculus originates in the vestibular nuclei. A second input of unknown origin conveys visual information about retinal slip. Thus, part of the flocculus -- as further discussed elsewhere (Waespe and Henn 1981) -- may be specialized to subserve visual-vestibular interaction to improve the nystagmus response. PMID- 6266857 TI - Visual-vestibular interaction in the flocculus of the alert monkey. II. Purkinje cell activity. AB - The activity of Purkinje cells (P-cells) was recorded in the flocculus of alert Rhesus monkeys under different conditions of visual-vestibular stimulation. Stimulations conditions were vestibular, optokinetic, combined and conflicting. About 10--20% of all P-cells were activated in their simple spike activity during conflicting stimulation to the recording side (type I) and gave no response or much less during vestibular stimulation. About half of these P-cells were also activated during optokinetic stimulation to the recording side at velocities above 40--60 deg/s. Simple and complex spike activity behaved in a reciprocal way with overlapping but not identical working ranges. Simple spike modulation was unidirectional, complex spike activity always bidirectional. Modulation of simple spike activity cannot be related to one single parameter of the sensory input or the oculomotor output. The hypothesis is put forward that the vestibular nuclei and the flocculus behave in a complementary fashion in processing visual vestibular information, the flocculus being specialized for high velocity optokinetic nystagmus and suppression of vestibular nystagmus. PMID- 6266859 TI - Effects of morphine and naloxone on spontaneous activity of fetal rats. PMID- 6266858 TI - Morphological changes in presynaptic terminals of the chick ciliary ganglion after stimulation in vivo. A stereological study showing a net loss of total membrane. AB - The Edinger-Westphal nucleus of one day old chicks was stimulated in vivo. This nucleus projects via the oculomotor nerve to the ciliary ganglion. The stimulation produces morphological changes in the calyciform endings located in the ciliary ganglion. There is a significant reduction of the numerical density on area of the clear and the dense core vesicles. The numerical density of the coated vesicles is low compared to that of the clear vesicles. Their density is however almost doubled by the stimulation. The vesicles, the vacuoles and the plasma membrane were quantified using stereological procedures. A net loss of total membrane was found due to the loss of organelle membrane not compensated for by an equivalent increase of the plasma membrane. These observations are discussed in terms of the theory of vesicular membrane recycling as proposed by Heuser and Reese (1973). PMID- 6266860 TI - The differential distribution of label following uptake of 3H-labeled amino acids in the dorsal cochlear nucleus of the cat. An autoradiographic study. PMID- 6266862 TI - Effects of axotomy on lamprey spinal neurons. PMID- 6266861 TI - Peripheral nerve fiber and spinal cord pathway contributions to the somatosensory evoked potential. PMID- 6266863 TI - Long-term effects of regeneration and prevention of regeneration on nucleolar morphology after facial nerve injury during development. PMID- 6266864 TI - Response of medial septal neurons to the iontophoretic application of glucocorticoids. PMID- 6266865 TI - Halothane actions in the rabbit hippocampus: correlative neurophysiologic and neurochemical effects. PMID- 6266866 TI - Phosphoprotein phosphatase activity of bovine intestinal alkaline phosphatase. AB - The phosphoprotein phosphatase activity of a commercial preparation of bovine intestinal alkaline phosphatase (EC 3.1.3.1) was examined using phosvitin and dentine phosphoprotein as substrates. Over 90% and 70% of the phosphorus from dentine phosphoprotein and phosvitin were hydrolyzed in 2 h. The optimum pH of the enzyme for the dephosphorylation of phosvitin and dentine phosphoprotein was nearly 6. No protein phosphatase activity was observed when the alkaline phosphatases from bovine liver and pulp were investigated. PMID- 6266867 TI - Galactose-l-phosphate uridyl transferase activity in red cells of various animal species. PMID- 6266868 TI - Na+ independent binding of [3H] muscimol to a membrane fraction of the brains of normal and dwarf mice. AB - Although their body weights were decreased by about 77% and their brain weights by about 30%, high-affinity [3H] muscimol binding to a cerebral membrane fraction was not altered in hereditary pituitary dwarf mice. Marked changes in the level of pituitary growth-associated hormones do not appear to be associated with a change in cerebral GABA-receptors. PMID- 6266869 TI - [Sulfanilamide absorption and acetylation in rats with experimental hyperlipidemia and cellular regulation of the process of acetylation]. AB - Experiments on an isolated ileum of the rat with experimental hyperlipidemia have shown the decreased acetylation rate of sulfalen, sulfamonomethoxin and sulfapyridazine. The absorption rate of the free forms of sulfanilamides was increased (significantly for sulfalen and sulfapyridazine). Isadrin (1 . 10(-8) M) and cAMP (1 . 10(-5) M) introduced into the liquid exposed to the mucosa of the rat ileum raised the acetylation rate of sulfamonomethoxin by the ileic wall while anaprilin (1 . 10(-6) M) led to the reduction of both absorption and acetylation of this sulfanilamide. Addition of cAMP to the incubation mixture of mitochondria and microsomes increased the acetylation rate of sulfamonomethoxin. PMID- 6266871 TI - The isolated F0 of Escherichia coli aTP-synthase is reconstitutively active in H+ conduction and ATP-dependent energy-transduction. PMID- 6266872 TI - Electric-field induced pK-changes in bacteriorhodopsin. PMID- 6266870 TI - [Prostaglandins and the nervous system (review of the literature)]. PMID- 6266873 TI - Evidence for a calcium-gated cation channel in sarcoplasmic reticulum vesicles. PMID- 6266874 TI - The reconstitution of human C1, the first complement component: binding of C1r and C1s to C1q influences the C1q conformation. PMID- 6266875 TI - A heat-stable inhibitor protein for bovine brain cyclic nucleotide phosphodiesterase from Escherichia coli. PMID- 6266876 TI - Formation of novel hydroxylated eicosatetraenoic acids in preparations of human polymorphonuclear leukocytes. PMID- 6266877 TI - Formation of thiobarbituric-acid-reactive substance from deoxyribose in the presence of iron salts: the role of superoxide and hydroxyl radicals. PMID- 6266878 TI - Identification and characterization of receptors for secretagogues on pancreatic acinar cells. AB - Acinar cells from guinea pig pancreas possess six different classes of receptors that mediate the actions of various secretagogues on enzyme secretion. Four classes of receptors stimulate enzyme secretion by causing mobilization of adenylate cyclase and increased cellular cyclic AMP. This paper summarizes the results of studies that have employed radiolabeled secretagogues of high specific activity and have measured directly the interaction of secretagogues with their receptors on pancreatic acinar cells. PMID- 6266879 TI - Receptors for cholecystokinin and insulin in isolated pancreatic acini: hormonal control of secretion and metabolism. AB - Both isolated pancreatic cells and isolated pancreatic acini have been prepared from mouse and rat pancreas. Although isolated cells are useful for the study of early events in stimulus-secretion coupling such as regulation of Ca2+ fluxes, they show a relatively poor ability to secrete digestive enzymes in response to secretagogues. Most likely this deficiency in secretion is due to the loss of specialization at the luminal plasma membrane surface. In contrast to isolated cells, isolated pancreatic acini can be used to study the secretion of digestive enzymes in response to hormones and neurotransmitters. Using isolated acini and a new preparation of radioiodinated cholecystokinin (CCK), we have been able to characterize pancreatic CCK receptors. Analysis of binding data reveals two orders of binding sites, a high affinity site (Kd = 64 pm) and a low affinity site (Kd = 21 nm). Stimulation of amylase release correlates with occupancy of the high affinity site. High affinity receptors for insulin are also present on isolated acini. After binding to these receptors, insulin stimulates protein and amylase synthesis. Insulin does not directly stimulate amylase secretion but rather potentiates the effects of hormonal secretagogues. These studies indicate, therefore, that isolated pancreatic acini can be employed to study in vitro various events in hormonal and neurotransmitter regulation of pancreatic enzyme secretion and metabolism. PMID- 6266880 TI - Effects of chemical transmitters on function of isolated canine parietal cells. AB - In view of the complexity of the regulation of gastric acid secretion, isolated parietal cells offer the appealing prospect of studying the receptors and mechanisms activating this cell after it has been removed from the confusing milieu of the intact mucosa. Histamine and cholinergic agents stimulate the function of canine parietal cells by interacting with typical H2 and muscarinic receptors. Gastrin produces only a small stimulation, interacting with a third, presumably specific, receptor. Combinations of histamine and carbachol and of histamine and gastrin produce potentiating interactions. When isolated parietal cells are treated with these combinations of agents, cimetidine and atropine display and apparent lack of specificity, reminiscent of that found in vivo, and probably resulting from interference with the histamine and cholinergic components of these potentiating interactions. The action of histamine, but not of carbachol or gastrin, is linked to stimulation of cyclic AMP production by parietal cells. Two potential inhibitors of acid secretion, secretin and prostaglandin E2, also stimulate cyclic AMP production, but these later effects appeared to occur largely in nonparietal cells. PGE2 however specifically inhibits histamine-stimulated parietal cell function, apparently by blocking activation of adenylate cyclase. Cholinergic action on the other hand is closely linked to enhanced influx of extracellular calcium. PMID- 6266881 TI - Efficiency of energy retention in genetically obese animals and in dietary induced thermogenesis. AB - Genetically obese rodents (ob/ob mice and fa/fa rats) and animals with dietary induced thermogenesis represent two extremes in efficiency of energy retention: the former deposit dietary energy with high efficiency, whereas the later deposit dietary energy with low efficiency. These differences in efficiency of energy retention must, at the cellular level, be associated with changes in efficiency and/or rate of formation and/or utilization of ATP (and other high energy intermediates). Brown adipose tissue possesses a unique proton-conductance pathway that reduces the efficiency of ATP synthesis. It has been speculated that this pathway is suppressed in obese (ob/ob) mice and accelerated in rats with dietary-induced thermogenesis. Metabolic reactions that alter the rate of ATP utilization in animals include Na+, K+-ATPase and protein turnover. The concentration of Na+, K+-ATPase enzyme unites in skeletal muscle and liver of young adult obese (ob/ob) mice is lower than in tissues of young adult lean mice. There also appear to be alterations in protein turnover in certain tissues of obese (ob/ob) mice, but additional studies are required to determine if whole body protein turnover is altered in these animals. Data are unavailable on either Na+, K+-ATPase or protein turnover in tissue of animals with dietary-induced thermogenesis. Continuation of studies in these areas should provide a metabolic basis for understanding individual variability in efficiency of energy retention. PMID- 6266882 TI - Getting high on running. PMID- 6266883 TI - Anterior pituitary hormone levels in the cerebrospinal fluid of patients with pituitary and parasellar tumors. AB - Cerebrospinal fluid (CSF) concentrations of growth hormone, prolactin (PRL), adrenocorticotropin, thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, and the glycoprotein hormone alpha subunit were determined in 30 patients with pituitary and parasellar tumors. Although many of the patients had elevated hormone levels, no differentiation between patients with intrasellar tumors and those with pituitary tumors with suprasellar extension or primary suprasellar tumors could be made based upon the absolute CSF hormone concentration. A highly significant correlation between serum and CSF PRL concentrations was found (r = 0.87; P less than 0.001), suggesting that CSF PRL is derived from the serum. No correlation was found between the serum and CSF concentrations of the other anterior pituitary hormones. PMID- 6266885 TI - In vitro method for evaluation of spermicides by hemolytic potency. AB - Nonoxynol-9 immobilizes sperm and hemolyzes erythrocytes at analogous concentrations; therefore, erythrocytes may be utilized for predicting in vitro spermicidal potency. Since erythrocytes (human or rabbit) are usually more readily available in larger quantities than are spermatozoa, this method permits extensive in vitro testing of different formulations of vaginal spermicides. PMID- 6266884 TI - Premature ovarian failure: evidence for the autoimmune mechanism. PMID- 6266886 TI - Attempts ot activate endogenous virus expression with Marek's disease virus DNA. AB - Several DNAs derived from Marek's disease virus-infected cells and tissues were tested for in vitro infectivity and for the ability to activate avian endogenous type C virus. The DNA isolated from tumour tissue, peripheral blood buffy coat cells, MDV-infected tissue cultures, lymphoblastoid cell lines and feather follicle epithelium cells from MDV-infected birds elicited a negative response in transfection assays. The MDV DNAs isolated did not activate the endogenous type C virus from cell cultures derived from the C, I and M chicken lines. Activation was observed only in one experiment in the early period after transfection with MDV DNA. The treatment with DNase destroyed this MDV DNA activity, and lambda phage DNA and cell DNAs did not activate the endogenous viruses. Repeated experiments failed to confirm the early activation of endogenous viruses. PMID- 6266887 TI - Chromosome aberrations in Chinese hamster embryonal fibroblasts after exposure to Rous sarcoma virus. PMID- 6266888 TI - Surface changes in cell membranes of Chinese hamster embryo fibroblasts, normal and transformed by Rous sarcoma virus, infected with influenza virus A2-Texas. PMID- 6266889 TI - Human papilloma virus type I purified from human genital warts. AB - Human wart virus (HPV) was isolated from a pool of genital warts. The electrophoretic mobility of virion proteins was studied by SDS polyacrylamide gel electrophoresis and showed the same pattern as that obtained with HPV-1. The analysis of DNA after restriction enzyme digestion with the endonucleases Hind III and Hae III, and nucleic acid hybridization did not show any difference with HPV-1. The viral particles were agglutinated by anti-HPV-1 serum, as shown by electron microscopic particle agglutination test. Furthermore, the immunological properties of this virus were investigated with guinea pig antiserum. Serologically, no antigenic cross-reaction between common and genital wart viruses were shown by immunodiffusion and immunofluorescence tests, whereas cross reactions were detected between plantar and genital wart viruses. These results allow to think that HPV-1 can induce plantar warts as well as genital warts. PMID- 6266890 TI - Variations of cAMP in epidermis and plasma of male adult subjects. AB - Over a time span of 66 h (sampling time at every 6th hour) the cAMP content in superficial skin punch biopsies of 8 male volunteers (medical students aged 20-30 years) and simultaneously the cAMP level in plasma were measured. By means of autocorrelation (2 alpha less than or equal to 5%) a circadian rhythm in the epidermal cAMP could be demonstrated. Sharp maxima were detected at midnight, whereas minima (not so clearly expressed) were seen at 6 a.m. A variation in plasma cAMP during the day was also established but no significant hint for a circadian rhythm could be found by autocorrelation. PMID- 6266892 TI - The effects of polyamines on the cyclic AMP efflux and metabolism in E. coli B cells. PMID- 6266891 TI - Biochemistry of ageing and cancer. PMID- 6266893 TI - Distribution, translocation and developmental changes of two types of the cyclic AMP-dependent protein kinases in chick liver. PMID- 6266894 TI - Studies on a membrane-bound nucleotidase from the marine bacterium MB 22. Comparison of a photometric and luminometric method for kinetic investigations. PMID- 6266895 TI - Microsomal phosphatidylethanolamine methyltransferase: effect of altered S adenosylmethionine-S-adenosylhomocysteine ratios in rat liver. PMID- 6266896 TI - Molecular mechanisms of chromatin assembly. PMID- 6266897 TI - Pivmecillinam plus pivampicillin in complicated urinary tract infection. Double blind comparison of the combination pivmecillinam/pivampicillin and pivmecillinam alone in patients with urinary tract infection. AB - Twenty-six surgical-urological patients with severe underlying diseases of the urinary tract and an acute urinary tract infection received a 10-day treatment with either pivmecillinam, 400 mg three times daily (twelve patients), or the fixed dose combination of pivmecillinam/pivampicillin (pivmecillinam 200 mg plus pivampicillin 250 mg) three times daily (fourteen patients). Eleven of the fourteen patients given combined therapy were cured bacteriologically, compared to only four out of twelve patients taking pivmecillinam alone. Clinical success was achieved in eleven out of fourteen patients who received combination therapy and in seven out of twelve subjects given pivmecillinam. Mild gastro-intestinal discomfort was recorded in a few patients in both treatment groups. The results suggest that the combination of pivmecillinam and pivampicillin is a promising alternative in patients with complicated urinary tract infections. PMID- 6266898 TI - Binding of iodinated rat and ovine prolactins to prolactin receptors and to its antibodies. AB - Most studies of prolactin receptors in rat tissues have not used the homologous 125I-labeled rat prolactin as tracers, but rather 125I-labeled ovine or human prolactin. We have compared the effect of different methods of iodination on the specific binding of rat and ovine prolactin to sites in the seminal vesicle of rats and the liver of mice post-partum. Ovine prolactin, either iodinated with lactoperoxidase or with mild chloramine-T (10 micrograms), showed 3 times the specific binding of correspondingly-iodinated rat prolactin. This greater sensitivity of rat prolactin to oxidative damage during iodination, as compared with ovine prolactin is further shown by the difference in Sephadex G-100 elution constant of unlabeled and labeled rat prolactin. . This difference was absent in the case of ovine prolactin. Parallel studies of the binding of the labeled hormone to homologous antibody revealed that immunoreactivity of labeled ovine prolactin was not affected by any of the iodination methods. Rat-prolactin immunoreactivity was depressed by lactoperoxidase iodination as compared with chloramine-T iodination. Rat prolactin was also less potent than ovine prolactin in inhibiting the binding of homologous and heterologous labeled hormone to its receptors, to a larger degree than could be expected from the bioassay potency of the various hormone preparations. These results reflect the greater sensitivity to damage of the biologically active site of rat prolactin, as compared with the ovine hormone. PMID- 6266899 TI - Increase in catecholamine-stimulated cyclic AMP and progesterone synthesis in rat granulosa cells during culture. PMID- 6266900 TI - Dibutyryl cyclic AMP-induced phosphorylation of specific proteins in adenohypophysial cells. AB - The objective of this work was to identify the natural substrates of cyclic AMP dependent protein kinase in pituitary cells. Studies were performed using 2 systems: intact pituitary cells stimulated with dibutyryl cyclic AMP (DBC) after preincubation with [gamma-32P]. Phosphorylation of proteins was analyzed by two dimensional gel electrophoresis, followed by autoradiography. In intact cells, the only clear and reproducible effect of DBC stimulation is increased phosphorylation of 3 proteins (termed A, B, and C), each with a molecular weight of about 20 000 dalton. The time-course and dose-dependence of phosphorylation of A, B and C are generally similar to that for DBC-induced hormone secretion, which is consistent with a role for these proteins in the secretory mechanism. When [gamma-32P]ATP is added to cell extracts, proteins A, B, and C are not measurably phosphorylated, either in the absence or presence of cyclic AMP. This observation suggests that proteins A, B and C may not be directly phosphorylated by cyclic AMP-dependent protein kinase, but may be phosphorylated indirectly by a second kinase. On the other hand, growth hormone and prolactin are readily phosphorylated in cell extracts by cyclic AMP-dependent protein kinase (although they are not phosphorylated in vivo). This finding makes clear the need for caution in interpreting results from broke cell systems. PMID- 6266901 TI - Electrophysiological evidence for the existence of separate receptor mechanisms mediating the action of 5-hydroxytryptamine. AB - The transepithelial potential recorded across the salivary gland of the blowfly Calliphora responded to 5-hydroxytryptamine (5-HT) with a complex depolarising response characterised by oscillatory activity at low doses. A rapid screening procedure for characterizing the electrophysiological response of the gland to 5 HT and its analogues was developed. It consisted of recording the potential during the gradual addition of the agent in the form of a ramp. 5-HT gave a characteristic electrophysiological signature which was then compared with that of other analogues. Tryptamine, bufotenine and dimethyltryptamine gave potential signatures very similar to those of 5-HT. Histamine, 4- and 5-fluoro-alpha methyltryptamine gave s predominantly hyperpolarising response which is characteristic of the effect produced by cyclic AMP. Analogues with substituents at the 5-position (methyl, methoxy, chloro) and 4-hydroxytryptamine gave a depolarising response indicative of a predominantly calcium effect. It is concluded that 5-HT acts through separate transducing mechanisms. The depolarizing response seems to indicate an action through calcium whereas the hyperpolarizing response might be mediated through cyclic AMP. Whether or not these separate responses are linked to different 5-HT receptors remains to be determined. PMID- 6266902 TI - A study of the induction of cell division in amphibian oocytes by insulin. PMID- 6266903 TI - Effect of the membrane lipid environment on the properties of insulin receptors. PMID- 6266904 TI - Viscosity differences between various guar gums. AB - Guar gum from four industrial sources was investigated. The viscosity of two preparations of hydrated guar gum in the form of powdered flour and one granulate flour was measured at 22 degrees and 32 degrees C and pH 1.0 and pH 4.0. Viscosity measurements on wax-coated guar granules proved impossible but visual assessment indicated an extremely low viscosity in all conditions. These findings were compared with the ability of the equivalent of 5 g guar gum of the various preparations to modify the absorption of a 50 g liquid glucose load. The mean post-prandial blood glucose curve was not significantly different from the control situation after the incorporation of each preparation. Despite the granulate flour attaining a considerably lower viscosity than the powdered flour they were equally effective in significantly reducing the mean post-prandial insulin curve (area under the curve (0-180 min) reduced by 46 and 50% respectively). The wax-coated granules which achieved minimal viscosity caused significantly less reduction of post-prandial insulin levels (area under the curve reduced by 37%). The viscosity of guar gum upon hydration is of importance in assessing the efficacy of a preparation in clinical use. PMID- 6266905 TI - Lysosomal enzyme activities and low density lipoprotein receptors in circulating mononuclear cells. Effect of insulin therapy in diabetic patients. AB - Methods for the measurement of the lysosomal enzymes acid cholesterol-ester hydrolase and N-acetyl-beta-glucosaminidase were adapted for use with freshly isolated circulating mononuclear cells. Activities of both these enzymes increased (to 259 and 147% of control values respectively) after 7 days of insulin therapy in diabetic subjects. Low density lipoprotein degradation by freshly isolated mononuclear cells increased simultaneously by 67% (p less than 0.05). The findings in this pilot study suggest [1] that circulating mononuclear cells can be used to evaluate the effect of metabolic changes in vivo on lysosomal enzymes and low density lipoprotein metabolism, and [2] that insulin can stimulate cellular lysosomal enzyme activity. PMID- 6266906 TI - The effect of phenoxybenzamine on the gastrin response to glycine stimulation. AB - The nature of adrenergic mechanism involved in gastrin release in response to local stimuli and feeding is still unclear. In the present study, the effect of phenoxybenzamine, a potent alpha-blocking agent, on the gastrin release in response to glycine perfusion (pH 7.0) of an isolated canine antral pouch was examined. The experiment was repeated with truncal vagotomy performed before glycine perfusion. It was found that gastrin concentrations measured via right gastroepiploic vein were significantly increased during phenoxybenzamine infusion with and without truncal vagotomy. This finding indicates the presence of an alpha-adrenergic mechanism which inhibits gastrin release when the antrum is locally stimulated. After the drug was discontinued, though there was an enhancement in gastrin response in both saline and glycine perfused groups, the peak gastrin levels were reached earlier in the vagotomized dogs. This finding might indicate the influence of vagus nerve during the experiment. PMID- 6266908 TI - Hepatic glycogen metabolism and its regulation by hormones in pouch young of the tammar wallaby, Macropus eugenii (Desmarest). PMID- 6266907 TI - Inhibition of intestinal secretion in rats by colchicine and vinblastine. AB - The role of microtubules in small intestinal electrolyte secretion was investigated in rats by testing the effects of colchicine and vinblastine, both of which inhibit microtubule assembly. In the intact rat, intraperitoneal injection of colchicine (5 mg/kg) inhibited cholera toxin and prostaglandin stimulated secretion without inhibiting their effects on adenylate cyclase or cAMP concentration. Pretreatment with colchicine had no effect on fluid transport in the absence of secretory stimuli. When added to rat ileum in vitro, colchicine reduced by 60% the short-circuit current (Isc) response to dibutyryl cAMP added 4 h later, whereas its structural isomer, lumicolchicine, which does not inhibit microtubule assembly, was ineffective. Vinblastine reduced by 55% the Isc response to dibutyryl cAMP and theophylline added 2 h later. Two hour pretreatment with vinblastine also reduced by 40% the Isc response to the cholinergic agonist, carbamylcholine, a Ca-dependent secretory stimulus which does not increase cAMP concentration. In contrast to their antisecretory actions, neither colchicine nor vinblastine inhibited glucose-stimulated active Na absorption. These results suggest a role for microtubules in active electrolyte secretion in the small intestine. PMID- 6266909 TI - Characterization of an autosomal rudimentary-shaped wing mutation in Drosophila melanogaster that affects pyrimidine synthesis. AB - A new autosomal mutation, rudimental (ral), which causes rudimentary-shaped wings in Drosophila melanogaster, has been isolated following ethyl methanesulfonate (EMS) mutagenesis. The wing phenotype of rudimental is identical to that of the X linked rudimentary (r) mutation, which affects the first three enzymes in the pyrimidine biosynthetic pathway. The autosomal mutant maps very close to ebony (3 70.7) at 70.42 on the right arm of chromosome 3. Analysis of the enzyme activities of orotate phosphoribosyltransferase (OPRTase) and orotidylate decarboxylase (ODCase) indicates that the rala26a allele has less than wild-type activity for both enzymes. This result is discussed in light of the fact that the OPRTase and ODCase activities are part of an enzyme complex, as are the carbamyl phosphate synthetase (CPSase), aspartate transcarbamylase (ATCase) and dihydroorotase (DHOase) activities, which are encoded by the complex rudimentary locus. We suggest that rudimental is also a complex lucus. PMID- 6266910 TI - Cryptic operon for beta-glucoside metabolism in Escherichia coli K12: genetic evidence for a regulatory protein. AB - Escherichia coli K12 does not metabolize beta-glucosides such as arbutin and salicin because of lack of expression of the bglBSRC operon, which contains structural genes for transport (bglC) and hydrolysis (bglB) of phospho-beta glucosides. Mutants carrying lesions in the cis-acting regulatory site bglR metabolize beta-glucosides as a consequence of expression of this cryptic operon (Prasad and Schaefler 1974). We isolated mutations promoting beta-glucoside metabolism that were unlinked to bglR; some of these mutations were shown to be amber. All of them were mapped at 27 min on the E. coli K12 linkage map and appeared to define a single gene, for which we propose the designation bglY. Utilization of beta-glucosides in bglY mutants appeared to be a consequence of expression of the bglBSRC operon, since bglB bglR and bglB bglY double mutants had the same phenotype. All bglY mutations analyzed were recessive to the wild type bglY+ allele. Phospho-beta-glucosidase B and beta-glucoside transport activities are inducible in bglY mutants, as they are in bglR mutants. Metabolism of beta-glucosides in both bglR and bglY mutants required cyclic AMP. We propose that bglY encodes a protein acting as a repressor of the bglBSRC operon, active in both the presence and absence of beta-glucosides, whose recognition site would be within the bglR locus. PMID- 6266911 TI - Intra- and interspecific variation of the mitochondrial genome in Rattus norvegicus and Rattus rattus: restriction enzyme analysis of variant mitochondrial DNA molecules and their evolutionary relationships. AB - Restriction endonuclease analysis has revealed extensive mtDNA polymorphism in two species of rats, Rattus rattus and Rattus norvegicus. Sequence divergence values for the eight detected R. norvegicus variants range from 0.2% to 1.8% and for the eight R. rattus variants, from 0.2% to 9.6%. Three of the most closely related R. norvegicus mtDNA's appear to differ by deletions/insertions of about 4 base pairs apiece. Restriction sites for seven enzymes have been mapped for 11 of these variants. The 31 intraspecific and 41 interspecific variant sites appear to be evenly distributed on the mtDNA molecule outside of the rRNA cistrons. The location of sites present in all the DNAs suggests that the rRNA genes and possibly the light strand origin of replication may be more highly evolutionarily conserved than other parts of the molecule. The sequence divergences among the mtDNAs of animals whose geographic origins are separated by major barriers, such as oceans, were significantly greater than those among animals found within large land masses, such as the continental United States. Dendrograms (phenograms), which have been constructed to depict the relationships among the various DNAs, indicate that East Asian members of the R. rattus species are more closely related to American rats of this species than to other Asian R. rattus animals from Sri Lanka. Moreover, it appears that R. norvegicus comprises a group taxonomically distinct from any of the R. rattus subspecies. PMID- 6266913 TI - Chromosomal distribution of the major insert in Drosophila melanogaster 28S rRNA genes. PMID- 6266912 TI - DNA polymorphism detectable by restriction endonucleases. AB - Data on DNA polymorphisms detected by restriction endonucleases are rapidly accumulating. With the aim of analyzing these data, several different measures of nucleon (DNA segment) diversity within and between populations are proposed, and statistical methods for estimating these quantities are developed. These statistical methods are applicable to both nuclear and nonnuclear DNAs. When evolutionary change of nucleons occurs mainly by mutation and genetic drift, all the measures can be expressed in terms of the product of mutation rate per nucleon and effective population size. A method for estimating nucleotide diversity from nucleon diversity is also presented under certain assumptions. It is shown that DNA divergence between two populations can be studied either by the average number of restriction site differences or by the average number of nucleotide differences. In either case, a large number of different restriction enzymes should be used for studying phylogenetic relationships among related organisms, since the effect of stochastic factors on these quantities is very large. The statistical methods developed have been applied to data of Shah and Langley on mitochondrial (mt)DNA from Drosophila melanogaster, simulans and virilis. This application has suggested that the evolutionary change of mtDNA in higher animals occurs mainly by nucleotide substitution rather than by deletion and insertion. The evolutionary distances among the three species have also been estimated. PMID- 6266914 TI - The transposons Tn501(Hg) and Tn1721(Tc) are related. PMID- 6266915 TI - Isolation of beta-globin-related genes from a human cosmid library. AB - A human gene library was constructed using an improved cloning technique for cosmid vectors. Human placental DNA was partially digested with restriction endonuclease MboI; size-fractionated and ligated to BamHI-cut and phosphatase treated cosmid vector pJB8. After packaging in lambda phage particles, the recombinant DNA was transduced into Escherichia coli 1400 or HB101 followed by selection on ampicillin for recombinant E. coli. 150 000 recombinant-DNA containing colonies were screened for the presence of the human beta-globin related genes. Five recombinants were isolated containing the human beta-globin locus and encompassing approx. 70 kb of human DNA. PMID- 6266916 TI - A deletion analysis of hybrid phage carrying the US region of Herpes simplex virus type 1 (Patton). I. Isolation of deletion derivatives and identification of chi-likes sequences. AB - The EcoRI-H fragment (15.4 kb) of Herpes simplex virus type 1 (HSV-1) has been cloned in lambda gtWES in both orientations. This fragment contains the entire US region and has about 900 bp of terminal redundant sequences derived from the internal and terminal repeats of the S region. 56 independent plaque-forming deletion derivatives of the lambda gt/WES::EcoRI-H hybrid phage were isolated using either EDTA resistance or ability to grow on Escherichia coli(P2) lysogens as selective methods. The endpoints of these deletions were located using nine restriction enzymes that cleave within the EcoRI-H fragment. All of the deletions have at least one endpoint within the cloned fragment. Several unusual features of the lambda hybrids, including heterogeneity of a particular region in the HSV 1 EcoRI-H fragment and the presence of chi-like sequences in the US region of HSV 1, are discussed. PMID- 6266917 TI - A deletion analysis of lambda hybrid phage carrying the US region of Herpes virus type 1 (Patton). II. Construction of an SmaI map. AB - The 15.4 kb EcoRI-H fragment of Herpes simplex virus type 1 (HSV-1) strain Patton, which contains the entire short unique (US) region, has been cloned in bacteriophage lambda. The fragment contains a terminal redundancy of about 900 bp that represents the S region terminal-repeat sequences. The restriction enzyme SmaI cleaves the EcoRI-H fragment at more than 30 sites. We have constructed an SmaI map of this fragment using thirteen isolates of lambda gtWES hybrid bacteriophage that carry various deletions of the EcoRI-H fragment. PMID- 6266918 TI - Extrachromosomal rDNA of Tetrahymena thermophila is not a perfect palindrome. AB - We have determined the restriction-endonuclease-cleavage map and the nucleotide sequence of the central 1.4 kb fragment of the macronuclear extrachromosomal rDNA of Tetrahymena thermophila. These data demonstrate that this molecule is not a perfect palindrome, having a 29 bp AT-rich non-palindromic sequence at its center. This observation is important in determining the mechanism by which a single chromosomally integrated rRNA gene in the micronucleus is rearranged and amplified during sexual development to yield multiple copies of extrachromosomal rDNA in the macronucleus. PMID- 6266919 TI - Plasmid vectors for positive selection of DNA inserts controlled by the lambda pL promoter, repressor and antitermination function. AB - Hybrid plasmids consisting of pBR322 or pOP203-3 and the EcoRI-D fragment of lambda DNA kill their bacterial host upon expression of a lambda gene (probably the kil function) located either between or across the SalI sites. The plasmids from surviving hosts are acquired deletions that remove the lambda kil gene or insertions that block the transcription of the kil gene. Some plasmids probably carry point mutations. Based on these findings, we constructed two vector plasmids, pKL1 and pHA10, which can be used for a direct positive selection of cloned fragments. These plasmids are particularly useful for the cloning and selection of N-unresponsive termination signals using BamHI and its isoschizomers. The DNA fragments cloned into these plasmids are under control of the strong pL promoter, which can be regulated by the lambda repressor, and the antitermination activity of the N gene product. PMID- 6266920 TI - Phage-lambda-mediated transduction of non-conjugative plasmids is promoted by transposons. PMID- 6266921 TI - Recovery of DNA fragments inserted by the "tailing" method: regeneration of PstI restriction sites. AB - A general method has been developed for the recovery of any DNA fragment inserted into a cloning vehicle containing a single endonuclease PstI site. Endonuclease PstI sites are regenerated by the addition of one or more deoxyguanosine residues to the 3' termini of the PstI-cleaved vehicle by terminal deoxynucleotidyl transferase. Chain elongation by terminal deoxynucleotidyl transferase is then continued with dITP, dATP or dGTP. A plasmid vehicle, pAO1, containing a single PstI site has been constructed. Insertional (foreign) DNA fragments that were "tailed" with dCTP have been annealed to PstI-cleaved pAO1 that was "tailed" with dGTP. When the annealed fragments were used to transform competent Escherichia coli cells, the single-stranded DNA gaps in the recombinant plasmids were repaired. Plasmids recovered from transformed bacteria could be cleaved by PstI into the insertional DNA with dG:dC tracts and linear pAO1 molecules. PMID- 6266922 TI - Cloning multiple copies of a DNA segment. AB - A method for self-ligation of DNA segments, which is based on the rotational non equivalence of ends produced by AvaI cleavage, has been developed. Using this method and an initiator molecule to encourage the formation of long polymers, we have obtained a plasmid containing 34 repeats of a 123-bp rat DNA segment. All of the repeats are in the same orientation, and the plasmid is quite stable. It should be possible to polymerize any DNA segment by this method. Potential uses of the procedure include production of large amounts of small, homogeneous DNAs for physical studies such as X-ray crystallography, and increasing the expression of cloned genes in bacteria. PMID- 6266923 TI - The gene for polypeptide IX of human adenovirus type 7. AB - This paper describes the nucleotide sequence of subgroup B human adenovirus type 7 (Ad7) between positions 3351-4010, and of cloned cDNA derived from mRNAs encoded by this segment. One of these (mRNA VII) is shown to be unspliced, and has its 5'- and 3'-ends encoded by positions 3460 (determined by the nuclease S1 technique) and 3939, respectively. The mRNA sequence contains a single open reading frame for protein biosynthesis between the first available initiation triplet AUG at position 3481 to the stop codon UAA at position 3895. It can specify a polypeptide of 138 amino acids (14 098 daltons) which must be polypeptide IX of Ad7, as is evident from its mapping position, and from a comparison with the sequence of the protein IX gene of subgroup C adenovirus type 5. PMID- 6266924 TI - The two-dimensional restriction analysis of Drosophila DNAs: males and females. AB - Two-dimensional restriction analysis has been applied to terminally labeled restriction segments from adult male and female flies that were the progeny of ten successive single-pair, brother-sister matings. Many of the 2500-4000 different bands that can be seen on autoradiographs are of widely different density, a fact that suggests the superposition of multiple restriction segments of similar sequence. The number of bands observed is significantly fewer than expected. Nearly all of the bands seen in male-DNA displays appear equivalent to those seen in female-DNA displays, but a few sex differences (male-dense and female-dense bands) can be identified--much fewer than expected. When the HpaII MspI test was applied to fractionated BamHI fragments, between 900 and 1800 discrete C-C-G-G sites were found to be cleaved in a completely equivalent fashion by each isoschizomer. PMID- 6266925 TI - Cloning of chicken globin cDNA in bacterial plasmids. PMID- 6266926 TI - Physical characterization of mini-mu and mini-D108. AB - Several derivatives of phages Mu and D108 have been isolated that carry an internal deletion generated by one of the IS1 components of a Tn9 transposon located in the A, B, or S gene of the prenatal phage. The deletions remove most of the lytic functions of the phage but leave intact either genes A and B or gene A and the left and the right end of the phages. These deleted derivatives, called mini-Mu and mini-D108, were physically characterized by electron microscopy and digestion with restriction enzymes. Mini-Mu and mini-D108, which carry an antibiotic resistance marker, are described and some of their genetic properties are summarized in the paper by Toussaint et al. (1981). PMID- 6266927 TI - Stabilization of a degradable protein by its overexpression in Escherichia coli. AB - Synthesis of proteins in Escherichia coli using recombinant DNA methodology has become an important tool for isolating and studying proteins. However, the E. coli protein degradation systems can interfere with the expression of cloned genes. To examine the effect of protein degradation, we have cloned the X90 allele of the E. coli lacZ gene. The X90 allele, an ochre mutant, codes for beta galactosidase lacking approx. 12 amino acids from the carboxyl terminus. The X90 protein is rapidly degraded in wild-type E. coli. Randomly sheared DNA fragments from lambda placZ-X90 were inserted into the EcoRI site of the plasmid pOP203-UV5 3, a derivative of pMB9 containing the lactose operator-promoter region. Recombinant plasmids that carry the lacZ-X90 gene were identified by the Lac+ phenotype of their transformants in an ochre-suppressor-containing host and the Lac- phenotype in Su degrees or supE hosts. One recombinant plasmid, p41, with an insert of 7.6 kb codes for the synthesis of the X90 promoter at a quantity equal to or greater than 50% of the total cellular protein of several strains. In contrast to the normal situation, the X90 molecules synthesized in great excess from the plasmid are stable in Su degrees hosts and can be recovered primarily from the 10 000 X g pellets of sonication lysates. The surprising stability of the overproduced X90 protein may be due to the formation of proteinaceous aggregates. PMID- 6266929 TI - Grown gall plant tumors of abnormal morphology, induced by Agrobacterium tumefaciens carrying mutated octopine Ti plasmids; analysis of T-DNA functions. AB - Ti plasmid mutants derived from Agrobacterium tumefaciens strain Ach5 that induce tumors of abnormal morphology have been analyzed. On tobacco, A. tumefaciens mutant strain LBA4060 induces tumors that specifically give rise to shoots. Shoots continue to grow from in vitro cultured bacteria-free tumor tissue derived from such tumors. The mutant character is shown to be correlated with the insertion of an A. tumefaciens IS element, IS60, into the left arm of the T region of the octopine Ti plasmid. Evidence is presented showing that IS60 is transferred into the plant cell DNA as part of the T-DNA. A second Ti plasmid insertion mutant A. tumefaciens strain LBA4210, with a Tn904 transposon in the center of the T-region, induces tumors that specifically exhibit a root development on tobacco plants. T-DNA has been detected in sterile amorphous crown gall tissue derived from these tumors. The transposon Tn904 insertion was shown to result a changed "core" T-DNA. Abnormal tumor morphologies induced by these mutant strains have been observed also on Kalanchoe stems. On tomato plants the mutants induce small unorganized tumors while on Nicotiana rustica unorganized tumors, nearly equal in size to those caused by the wild-type strain have been induced. LBA4060 was shown to be avirulent on Kalanchoe leaves and LBA4210 was weakly virulent. Infection of Kalanchoe leaves or tomato plants with a mixture of separately grown cultures of both mutants resulted in the formation of more or less normal tumors. The exposure of a tomato plant to naphthalene acetic acid (NAA), a synthetic auxin, during development of tumors induced by LBA4060 stimulated tumor formation. Tumor growth induced by LBA4210 was found to be stimulated by kinetin. PMID- 6266928 TI - Cloning the quinic acid (aq) gene cluster from Neurospora crassa: identification of recombinant plasmids containing both qa-2+ and qa-3+. AB - A 22.2-kb insert of Neurospora crassa DNA containing at least two of the genes from the inducible catabolic quinic acid pathway has been cloned into the cosmid vehicle pHC79 resulting in a recombinant plasmid, pMSK308. The qa-2+ locus (which encodes catabolic dehydroquinase) is functionally expressed in both Escherichia coli and qa-2 mutants of N. crassa transformed with pMSK308 plasmid DNA. Expression of the qa-3 gene (which encodes quinate dehydrogenase) is only detected upon reintroduction into N. crassa. Results were also obtained which suggested that the qa-4 gene, which maps between qa-2 and qa-3, may also be present on both pMSK308 and the previously described plasmid pVK88. Certain anomalies in the types of N. crassa transformants obtained with pMSK308 plasmid DNA were noted. PMID- 6266930 TI - Cloning and organization of genes for 5S ribosomal RNA in the sea urchin. Lytechinus variegatus. AB - A 1.35-kb EcoRI fragment of Lytechinus variegatus DNA containing a single 5S rRNA gene has been cloned into the plasmid vector pACYC184. Four clones from different transformation experiments contain 5S rDNA inserts of about the same size and have the same restriction enzyme digestion patterns for the enzymes HaeIII, HinfI, HhaI, and AluI. One EcoRI site near the HindIII site of the plasmid vector pACYC184 is missing in all the four clones. By DNA sequencing, the missing EcoRI ws found to be EcoRI site, d(AAATTN)d(TTTAAN) in pLu103, one of the four 5S rDNA clones. The structure of pLu103 was determined by restriction mapping and blot hybridization. Three restriction fragments, 1.0-kb HaeIII/HaeIII, 0.375-kb AluI/AluI and 0.249-kb MboII/MboII, which contain the 5S rRNA coding region, have been subcloned into the EcoRI site of the plasmid pACYC184. The organization of 5S rRNA genes in the sea urchin genome was also investigated. It was found that restriction endonuclease HaeIII has a single recognition site within each 5S rDNA repeat, and yields two fragment lengths, 1.2 and 1.3 kb. The behavior of these 5S rRNA genes when total L. variegatus DNA is partially digested with HaeIII is consistent with an arrangement of 5S rRNA genes in at least two tandemly repeated, non-interspersed families. Both the coding region and spacer region of the 5S rRNA gene in pLu103 hybridize to 1.2 and 1.3-kb rDNA families. This indicates that the cloned EcoRI fragment of 5S rDNA in pLu103 represents one single repeat of 5S rDNA in the genome. PMID- 6266931 TI - T cell mediated cytotoxic immune reactivity of bone marrow reconstituted chimeric mice. AB - The capacity of bone marrow reconstituted chimeric mice to mount sendai virus specific H-2 restricted as well as alloreactive cytotoxic T-cell responses has been investigated. Chimeras of the type a leads to (a x b)F1 and (a x b)F1 leads to a were used. In addition chimeras produced with (a x b)F1 mice grafted under the kidney capsula with a type parental thymus, thymectomised, lethally irradiated and reconstituted with either a, (a x b)F1 or b type bone marrow cells were tested. In agreement with the data of Zinkernagel and Bevan it was noted that virus specific T cells of semi-allogeneic chimeric mice are able to recognise virus antigens in the context of the MHC of the thymus in which they have maturated. The unexpected finding was that fully allogeneic chimeras were able to mount both alloreactive CTL and H-2 restricted, virus specific CTL. The H 2 restricted CTL detected were preferentially restricted to their own MHC type. In some animals also virus specific CTL restricted to the allogeneic thymus MHC type were observed. Data are also presented to indicate that longterm cultured bone marrow cells have the potential to repopulate lethally irradiated mice. PMID- 6266932 TI - Demonstration of plasma human chorionic gonadotropin beta-subunit during pregnancy using LH-hCG receptors from immature porcine testis. AB - In an attempt to provide better assessment of human chorionic gonadotropin beta subunit (hCG-beta) secretion in pregnant women, a method was developed for complete removal of hCG by porcine-purified receptors before measurement of the free hCG-beta subunit by radioimmunoassay. Blood samples of 111 pregnant women were collected and the following results were obtained: (1) Extensive removal (over 96%) of hCG allows quantitative determination of the free hCG-beta subunit by a specific radioimmunoassay. Our data demonstrate the presence of circulating hCG-beta subunit during pregnancy, a fact that was still under controversy until now. (2) In contrast with the hCG profile drug during pregnancy the free hCG-beta subunit exhibits a plasma concentration peak (400 +/- 132 ng/ml; mean +/- 1 SD) at the 12th-13th week, indicating that the changes in plasma levels of intact hCG and free hCG-beta subunit are unrelated. PMID- 6266933 TI - [Red blood cells and activated oxygen (author's transl)]. PMID- 6266934 TI - [An unusual case of peripheral neuropathy]. AB - A patient with peripheral neuropathy, weakness and skin pigmentation due to proven arsenic poisoning is presented. PMID- 6266935 TI - Some factors influencing production of sulphate by oxidation of elemental sulphur and thiosulphate in upper horizons of spruce forest soils. AB - Some factors influencing the oxidative activity of upper horizons of spruce forest soils (a mixture of fermentative and humus layers) toward intermediates of the oxidative part of the sulphur cycle were investigated. Preincubation of the soil with added cysteine, sulphide, elemental sulphur or thiosulphate was found to stimulate enzyme systems oxidating any of these compounds. Sulphite and sulphate were ineffective in this respect. The oxidation of elemental sulphur was stimulated by CaCO3, technical urea and high doses of superphosphate and potassium sulphate. It was inhibited by KH2PO4, pure urea, 40 % potassium salt, ammonium nitrate with calcium carbonate and the fertilizer NPK I. It proceeded at the highest rate at approximately 60 % capillary capacity (61 % of mass water content). Oxidation of thiosulphate was stimulated by KH2PO4, pure urea, superphosphate, potassium sulphate and only slightly by the fertilizer NPK I. It was inhibited by CaCO3, 40 % potassium salt and only slightly by ammonium nitrate with calcium carbonate. Potassium chloride, glucose and technical urea were without effect. The oxidation proceeded at the highest rate at 35 % maximal capillary capacity (48 % mass water content). PMID- 6266936 TI - Enhancement of 1,2-dimethylhydrazine-induced colon carcinogenesis in mice by dietary agar. PMID- 6266937 TI - [Carcinogenesis in the pancreas]. AB - The pancreatic carcinogen DHPN (dihydroxypropylnitrosamin) was administered to Syrian golden hamsters. By intragastric administration more pancreatic carcinomas in the head of the gland were induced than by subcutaneous injections. After choledochojejunostomy the incidence of carcinomas was only 5--7% and the lesions were similar in multiplicity and distribution without relationship to the way of administration. The importance of biliary reflux in pancreatic tumor induction is discussed and the role of bile concerning the preferred localisation of the tumors in the head of the pancreas. After ligation of the main pancreatic duct in the splenic lobe, the incidence, location and type of proliferative lesions distal and proximal to the ligature were recorded and compared to those of DHPN treated hamsters without duct ligation. Proliferative duct lesions, including carcinomas, developed on either side of the ligation. While after subcutaneous administration the incidence was similar to the in nonligated animals, a markedly decreased incidence was found in orally treated animals with duct ligation. The findings show that DHPN reaches the pancreatic duct cell via blood circulation. Furthermore, it is suggested that an unimpaired release of pancreatic juice in the duodenum is necessary for the enteral resorption of DHPN. Referring to clinical data and according to the results of these experiments the procedure of choice in pancreatic surgery is total pancreatectomy in case of the local operable malignant pancreatic tumor. Otherwise from the pancreatic remnant after Whipple's procedure pancreatic carcinoma may develop again from precancereous lesions. PMID- 6266938 TI - Adenylate cyclase responsiveness of human insulinomas. AB - Adenylate cyclase activity was assayed in a crude particulate fraction of one benign and one malignant human insulinoma. Adenylate cyclase of both tumours responded to 5'-guanylyl-imidodiphosphate, sodium fluoride, glucagon and prostaglandin E2, and in addition the adenylate cyclase of the benign tumour responded to isoprenaline. Glucose and prostaglandin I2 (prostacyclin) did not stimulate the adenylate cyclase in either tumour, although prostaglandin I2 stimulated insulin secretion in cultures of the benign tumour. The in vitro responsiveness of the adenylate cyclase to glucagon did not correlate closely with the effect of glucagon on insulin secretion in vivo. PMID- 6266939 TI - Post receptor activation of lipolysis in starvation, diabetes mellitus and hyperthyroidism. AB - Activation of lipolysis by cyclic AMP in conditions with accelerated lipid mobilization was examined in subcutaneous adipose tissue incubated in vitro. In (a) 16 obese patients before and during therapeutic starvation, (b) 18 diabetics before and after antidiabetic treatment and (c) 11 hyperthyroid patients before and after anti-thyroid treatment, a positive correlation was found between stimulation of basal cyclic AMP accumulation and stimulation of basal glycerol release using either isopropyl noradrenaline or noradrenaline (r = 0.6-0.9). During antidiabetic treatment stimulation of lipolysis increased in relation to that of cyclic AMP accumulation (F = 10.1, p less than 0.01), whereas during antithyroid therapy there was a decrease (F = 95.2, p less than 0.01). Starvation did not alter the relationship between lipolysis and cyclic AMP in hypogastric adipose tissue whereas in femoral tissue stimulation of lipolysis decreased in relation to that of cyclic AMP accumulation (F = 9.6, p less than 0.01). It is concluded that the amount of cyclic AMP needed to promote lipolysis is increased during starvation and in diabetes mellitus but is decreased in hyperthyroidism. From the studies during starvation it appears that regional differences in the post-receptor activation of lipolysis exist in human adipose tissue. PMID- 6266940 TI - Effect of the growth hormone-secreting tumor StW5 on pituitary and adrenal gland function in rats. AB - A growth hormone-secreting tumor (StW5 was implanted into male rats and resulted in a tripling of adrenal weight concomitant with a 30% decrement in pituitary weight. Plasma concentrations of corticosterone in tumor-bearing (TB) rats were significantly elevated at rest or after ACTH injections or the stress of either anesthesia. The rise in plasma concentrations of corticosterone was due mainly to the large increment in adrenal size although a significant increase in adrenal responsiveness to ACTH was demonstrated in vitro. In addition, plasma corticosterone concentrations were higher in TB rats despite both a doubling of the blood volume and a 50% increase in liver capacity to metabolize corticosterone. Pituitary ACTH content was significantly lower in TB rats, but these pituitary glands could still release near-normal quantities of ACTH as shown both by in vitro incubations and adrenal corticosterone output following ether stress. PMID- 6266941 TI - Changes in testicular hCG binding and Leydig cell function in rats throughout life. AB - The age dependence of Leydig cell function was investigated in rats from prepuberty (15 days) to senescence (39 months). Serum LH, serum and testicular testosterone were measured by radioimmunoassay. The binding capacity and affinity of LH/hCG receptors were determined by a radioligand receptor assay (hCG/Leydig cells) using 125I-hCG labelled by the lactoperoxidase method. Separation of bound and free 125I and simultaneous concentrations of 125I-hCG was achieved by vacuum ultrafiltration. The biochemical integrity of 125I-hCG tracer was ascertained by various chromatographic procedures. The highest hCG-finding and highest serum LH levels were found during puberty. Serum and testicular testosterone concentrations, however, were maximal in early adulthood. From this period onwards to late senescence hCG-binding changed only slightly, while serum LH and testosterone levels decreased significantly towards late senescence. The study shows that, although hCG binding to the Leydig cell changes characteristically during development, it is minimally affected by aging and cannot therefore be responsible for the reduced androgen biosynthesis in senescence. PMID- 6266942 TI - Therapeutic uses of immune suppression and enhancement. PMID- 6266943 TI - Chromosome analyses and anchorage-independent growth of SV40-induced morphologically transformed epithelial cells from amniotic fluids. AB - Epithelial cells from amniotic fluid cell cultures are morphologically transformed by simian virus 40, 20 to 30 d after infection. The cells of the transformed colonies are highly basophilic, have a high nuclear-to-cytoplasmic ratio, and show a dense growth pattern. The cells are virus producers, and ultimately, after continuous passage, the cell lines reach a crisis situation with no growth. Twelve morphologically transformed cell colonies were isolated from five different individuals for chromosome analyses after approximately 18 population doublings (second bottle passage). For all cell lines diploid cells were observed. Banding of the chromosomes revealed normal morphology of euchromatic and heterochromatic regions. The suggestion is made that chromosome alteration is not necessary, nor a prerequisite, for the morphologically transformed phenotype to be expressed and that the transformation process per se causes chromosomal instability. Tests for colony formation of the 12 cell lines in semisolid medium showed that different transformed colony isolates from the same individual donor of the cells either formed or did not form colonies in agar. The size of the colonies was also consistent within individuals as compared to between individuals. These limited results are suggestive of a dependence upon the genetic constitution of the individual donor of the cells for colony formation in soft agar. PMID- 6266944 TI - Gliomas of astrocytic series : a review of 86 cases. PMID- 6266945 TI - Hepatoblastoma: an attempt at characterization. PMID- 6266947 TI - Chondroid syringoma (mixed tumour) of radius. PMID- 6266946 TI - Non-simultaneous primary malignancies. PMID- 6266948 TI - Studies on the in vitro development of rat peritoneal mast cells. AB - Mast-cell-depleted rat peritoneal exudate cells have been shown to differentiate into pure mast cell cultures when placed in a special medium containing 15% horse serum and 20% L-cell supernatants. In the present communication, the changes that occur within the cells during culture are examined by several parameters. Prior to culture, the cells resemble mononuclear phagocytes morphologically. During culture, their total cell volume and cytoplasmic mass increase, and they develop metachromatic, alcian blue and later on safranin-positive cytoplasmic granules. Proliferation of the cells, as shown by 3H-thymidine incorporation, is optimal between days 3 to 11, and is decreased by changing the composition of the medium or by adding high concentrations of histamine (greater than 10-6M) and heparin (greater than 50 millimicron/ml). By cytochemical staining and by analysis of subfractionated cellular components, eosinophil chemotactic factor (ECF), histamine, beta-glucuronidase, alpha-naphthyl acetate esterase and myeloperoxidase are demonstrated, mostly within the granules. The findings suggest a close morphological and functional relationship between peritoneal mast cell precursors and mononuclear phagocytes. PMID- 6266949 TI - Restriction of foetal calf serum-induced cytotoxicity by human T-cells. PMID- 6266950 TI - Seroepidemiologic study of herpes simplex virus type 1 and 2 in Delhi. PMID- 6266952 TI - A serological study of cytomegalovirus infection at Lucknow. PMID- 6266951 TI - Antibody response in ardeid birds following experimental infection with Japanese encephalitis virus. PMID- 6266953 TI - Effects of tonin, an angiotensin II-forming enzyme, on vascular smooth muscle in the normal rabbit. AB - Tonin is an enzyme of the serine protease family present in different rat tissues which releases angiotensin II (AII) directly from angiotensinogen and the tetradecapeptide renin substrate and from angiotensin I (AI). Tonin potentiates the effect of norepinephrine (NE) in the rat mesenteric artery preparation and in the aortic strips from normal and hypertensive rats. In rabbit aortic and mesenteric artery strips tonin potentiates the effect of NE, almost doubling its response. A similar effect was observed on the KCl and AII-induced contraction. This tonin-induced potentiation is reversible and long-lasting, persisting for 1 to 2 hours after being added into the tissue bath. In 75% of the vascular strips assayed, tonin elicited a contraction with a short latency period and with a maximum tension ranging from a few milligrams to over 1 g. To clarify the mechanisms of tonin effect on vascular smooth muscle, a variety of agents have been used. Neither indomethacin, saralasin, nor alpha- or beta-adrenergic blockers changed the direct contraction or the potentiation induced to NE. Db cAMP and theophylline blocked the potentiation to the response to NE. A Ca2+-free medium, La3+, and verapamil produced a 75% inhibition of the direct tonin-induced contraction. Papaverine, isoproterenol, and theophylline relaxed the same contraction. Enzymatic inactivation of tonin blocked completely the direct contraction but not the potentiation to NE. These experiments suggest that the vasoactive effect of tonin may be mediated by the release of intracellular-bound calcium, an effect dependent on a proteolytic effect of tonin, and by increasing the cellular permeability to calcium, which is not of a proteolytic effect. It is suggested that tonin remains attached to the vascular strips by mechanisms as yet not clarified. PMID- 6266954 TI - Preferential noradrenergic innervation of alpha-adrenergic receptors in vascular smooth muscle. AB - In the isolated perfused hindlimb preparation of the dog, pressor responses to norepinephrine (NE) are mediated by postsynaptic alpha 1- and alpha 2-adrenergic receptors. Results obtained using preferential alpha 1- and alpha 2-adrenergic receptor antagonists suggest that the alpha 1-subtype is predominantly innervated while both alpha 1- and alpha 2-adrenergic receptor subtypes in vascular smooth muscle are accessible to circulating agonists and antagonists. Preliminary studies in the isolated perfused cat spleen support these in vivo findings in the dog. In contrast to vascular smooth muscle, the cat nictitating membrane appears to contain only alpha 1-adrenergic receptors postsynaptically. PMID- 6266955 TI - Enhanced alpha-adrenoreceptor-mediated vasoconstriction in essential hypertension. AB - Forearm blood flow (FAF) has been determined using venous occlusion plethysmography in 24 patients with essential hypertension (EHT) and in 16 age matched normotensive subjects (NT) under basal resting conditions, following nonspecific vasodilatation with sodium nitroprusside and after intraarterial infusion of the postjunctional alpha-blocking drug, prazosin. Under basal conditions, FAF was significantly higher in EHT than in NT. Infusion of sodium nitroprusside produced a similar absolute increase in FAF in both groups, whereas postjunctional alpha-blockade with prazosin led to a significantly greater increase in FAF in EHT than in NT. A positive correlation was found between plasma epinephrine concentration and prazosin-induced FAF in EHT but not in NT. These results suggest an enhanced postjunctional alpha-adrenoreceptor-mediated vasoconstrictor component in established EHT. PMID- 6266956 TI - Effect of prolonged dietary administration of vanadate on blood pressure in the rat. AB - Vanadate, a potent naturally occurring Na+,K+-ATPase inhibitor thought to have a role in regulating Na+-K+ pump activity, was fed to uninephrectomized rats drinking tap water or a 1% solution of sodium chloride for as long as 56 weeks. Feeding was achieved by adding sodium orthovanadate to normal rat chow equivalent to 100 or 200 ppm vanadium by weight. In the rats drinking tap water, systolic pressure gradually increased over a period of several weeks and then was sustained in a dose-related manner for the duration of the treatment. The increased pressure was not associated with changes in water intake, urine output, or urinary sodium excretion but correlated positively with plasma vanadium levels ranging from 0.04 to 0.27 microgram/ml. Increased pressure was associated with increased heart-to-body-weight ratio but did not appear to occur in a small group of animals drinking the 1% solution of sodium chloride. These findings, considered in the light of others, indicate that vanadate deserves continued study in relation to hypertension. PMID- 6266957 TI - Possible role of kinins in circulatory homeostasis. State of the art review. PMID- 6266958 TI - Renin-angiotensin and adrenergic mechanisms in control of blood pressure in fowl. AB - Many avian species demonstrate atherosclerosis and high blood pressure (BP) that are influenced by age, sex, diet, and environment, but show no arteriosclerosis in small vessels. Thus, we aimed to define neural and humoral control of BP in conscious, 32-wk-old female chickens, Gallus gallus. Mean aortic pressure (determined by chronically implanted catheter) was 137.6 +/- 2.0 mm Hg; heart rate was 295 +/- 4 beats/min. Plasma renin activity (PRA), measured by radioimmunoassay of fowl angiotensin I ([Asp1, Val5, Ser9]AI), and plasma angiotensinogen levels were 3.55 +/- 0.31 ng/ml/hr and 1229 +/- 66 ng/ml respectively. Repeated injection of propranolol (4 to 8 mg/kg/day, i.m.) decreased (p less than 0.01) the BP 19.1 +/- 3.0 mm Hg and heart rate 76 +/- 6 beats/min. Acute infusion of propranolol also markedly reduced BP and heart rate, and increased plasma levels of norepinephrine and epinephrine. SQ 14,225 (20 mg/kg/day) reduced BP (p less than 0.01), but BP returned towards original levels unless a higher dose was given. PRA increased 2- to 6-fold. BP also decreased 31.0 +/- 2.1 mm Hg after reserpine treatment, but not after [Sar1, Ile8]AII. These results suggest that in maintaining BP in fowl the beta-adrenergic function is important, whereas the renin-angiotensin system may not have a primary role. PMID- 6266959 TI - Inhibition of human converting enzyme in vitro by a novel tripeptide analog. AB - We have studied inhibition of homogeneous human converting enzyme by a new inhibitor, a ketomethylene derivative of the blocked tripeptide substrate, Bz-Phe Gly-Pro (ketoACE). KetoACE inhibited the hydrolysis of Hip-His-Leu and Hip-Phe Arg at different concentrations (I50 values were 4 X 10(-8) M and 2 X 10(-7) M, respectively). Kinetic studies indicated that ketoACE inhibits the hydrolysis of both substrates by a similar, non-competitive mechanism. At the lowest enzyme concentration tested, using 3H-Hip-Gly-Gly as substrate, the I50 of ketoACE was 6 X 10(-9) M. KetoACE protected a functional tyrosine residue in the active site of human converting enzyme from modification with N-acetylimidazole. It is proposed that there are alternate (hydrophobic) binding sites for both inhibitors and substrates in the active site of human converting enzyme. It should be possible to develop other high-affinity inhibitors of this class that bind to hydrophobic sites and do not require metal binding via a sulfhydryl group. PMID- 6266960 TI - Regulation of aldosterone biosynthesis during sodium deficiency. Evidence for an essential role of the pituitary gland. AB - The aldosterone response to adrenocorticotropic hormone (ACTH) and angiotensin II (AII) was evaluated in patients with pituitary insufficiency before and after dietary sodium restriction (10 mEq Na+/day for 12 days). On normal sodium intake, plasma aldosterone concentration and plasma cortisol concentration failed to change from control levels in response to a single injection of ACTH or to a continuous 1-hour infusion of AII in patients with pituitary insufficiency. In response to dietary sodium restriction for 12 days, plasma renin activity (PRA) increased fivefold in patients with pituitary insufficiency, while plasma aldosterone concentration failed to increase significantly, averaging 11.0 +/- 3.1 before and 12.3 +/- 3.7 ng/dl (ns, p greater than 0.05) after sodium deficiency. Although aldosterone secretion failed to increase during sodium deficiency, the patients came into balance at 10 mEq without a significant change in arterial blood pressure (BP). In sharp contrast to the lack of aldosterone response to ACTH before sodium deficiency, plasma aldosterone concentration increased markedly from 12.9 +/- 3.3 to 156 +/- 17.3 ng/dl (p less than 0.001) in response to ACTH after sodium deficiency. Although the adrenal glomerulosa cells were markedly sensitive to ACTH during sodium deficiency, they remained almost totally refractory to AII since aldosterone secretion failed to increase significantly in response to continuous infusion of a pressor dose of AII for 1 hour. Replacement therapy with ACTH gel for 3 months in patients with pituitary insufficiency failed to restore a normal aldosterone response to either ACTH or AII. These data demonstrate that some non-ACTH pituitary factor(s) is essential for a normal aldosterone response to ACTH, AII, and sodium deficiency. PMID- 6266961 TI - Role of Fc fragments in antibody-mediated recovery from ocular and subcutaneous herpes simplex virus infections. AB - The contributions of the Fc fragment of virus-specific antibody in the resistance of mice to peripheral herpes simplex virus infection were investigated. Rabbit anti-herpes simplex virus-specific F(ab')2 fragments prepared by pepsin digestion of immune immunoglobulin G (IgG) were found to be inactive in complement-mediated cytolysis while retaining their capacity to neutralize virus infectivity in vitro. When F(ab')2 fragments were passively transferred either before or simultaneously with virus inoculation, they were as efficient as intact IgG was in protecting animals from virus challenge. However, if passive transfer was delayed until 8 h after herpes simplex virus infection, only IgG antibody was protective. The loss of protective activity could not be attributed to a rapid disappearance of F(ab')2 fragments, because comparable levels of F(ab')2 fragments and IgG antibody were maintained in the blood of recipients during the time that antibody mediated its protective effects. The inability of F(ab')2 subunits to activate complement was also not a factor, because complement deficient A/J mice and complement-sufficient SJL/J mice recovered from herpes simplex virus infection after the passive transfer of IgG. We concluded that the Fc component of the antibody molecule is needed to resolve intracellular infection and that the mechanism by which antibody mediates recovery remains undefined but does not appear to involve virus neutralization or complement activation. PMID- 6266963 TI - Variation in human rotavirus electropherotypes occurring between rotavirus gastroenteritis epidemics in central Australia. AB - The changes in human rotavirus electropherotypes, occurring during a period including two rotavirus gastroenteritis epidemics in 1976 and 1979 in relatively remote Central Australia, were determined by polyacrylamide gel electrophoretic analysis of the rotavirus genome ribonucleic acid. A number of different electropherotypes were present during each of the epidemics, although a single type was predominant in each one. The predominant electropherotype of the first epidemic persisted in the area for approximately 2 years afterwards. Apart from this electropherotype, only three others were recognized in the 3 years between the two epidemics. One of these, first seen 1 year before the second epidemic, bore a very close similarity to the predominant type of the second epidemic. Altogether, 12 different electropherotypes were recognized during the period of the survey. No type common to both areas was found when rotavirus electropherotypes recognized in Central Australia were compared with those detected in a 1973-to-1979 survey in Melbourne, Australia. PMID- 6266962 TI - Comparative neurovirulence of selected vesicular stomatitis virus temperature sensitive mutants of complementation groups II and III. AB - Weanling mice were inoculated intracerebrally with selected vesicular stomatitis virus (VSV) complementation group II and III temperature-sensitive (ts) mutants. Of the VSV ts mutants studied, only ts G32, a group III complementation mutant, appeared neurovirulent. Interestingly, neither the capacity to replicate in central nervous system tissue nor the ability to replicate in certain neurally derived continuous cell lines at semipermissive or nonpermissive temperatures appeared different among the VSV ts mutants employed. Finally, the pathological alterations in central nervous system tissue produced by VSV ts G32 were entirely different than those produced by G31 VSV ts in the group III mutant. These studies support the hypothesis that both the virological and neuropathological features produced by different VSV ts mutants are dependent upon the unique characteristics of each mutant, rather than upon a common biochemical defect shared by all members of a complementation group. PMID- 6266964 TI - Complement-fixing antibody to the AG-4 antigen in herpes simplex virus type 2 infected patients. AB - Sera collected from confirmed herpes simplex virus type 2 (HSV-2) patients were found to be devoid of complement-fixing antibody to the AG-4 antigen at the time of the herpes lesion outbreak in 10 out of 13 cases. However, 1 to 4 weeks after HSV-2 lesion appearance, 28 out of 30 patients acquired complement-fixing antibody to the AG-4 antigen. The sera of these patients contained immunoglobulin M antibody activity and the ability to immunoprecipitate a 160,000-molecular weight early HSV-2 antigen (the AG-4 antigen). Also, these sera were used to show that a variety of anti-herpes virus compounds had a negligible effect on AG-4 production in HSV-2-infected HEp-2 cells. The majority of the compounds tested (including acycloguanosine and phosphonoformate) are known to inhibit late antigen production, suggesting that the AG-4 antigen is an early antigen. It is probably an immediate early antigen (alpha) as it is formed in the presence of cycloheximide and actinomycin D, a treatment which is used to accumulate alpha proteins. PMID- 6266965 TI - Biological activity of Bordetella pertussis in lipopolysaccharide-resistant mice. AB - Effects of Bordetella pertussis organisms, such as adjuvanticity, induction of hypersplenia, and leukocytosis as well as modification of nonspecific resistance to infection and typical morphological response of lymphatic organs, were studied in the lipopolysaccharide-resistant C3H/HeJ mouse strain. It was shown that B. pertussis exerted all of these effects in C3H/HeJ mice, although the morphological response, hypersplenia, and modification of resistance to infection with Listeria monocytogenes in such animals were less pronounced than those in lipopolysaccharide-sensitive mouse strains. This indicated that the biological activity of B. pertussis as determined in the present studies, is due partly to structural components other than lipopolysaccharide. PMID- 6266966 TI - Murine cytomegalovirus infection: hematological, morphological, and functional study of lymphoid cells. AB - Mice were studied for 3 to 4 months after murine cytomegalovirus (MCMV) infection. Serial hematological parameters were evaluated. It was found that MCMV infection of mice were accompanied by the appearance of many atypical lymphocytes similar to those seen in association with the hematological features of mononucleosis associated with human CMV infection. Certain functions of splenocytes were studied in infected and uninfected animals during the 4 months after MCMV infection. Three periods were identifiable by the functional response of splenocytes during the course of MCMV infection. The initial phase was characterized by an elevated response of splenocytes to a T cell mitogen and a B cell mitogen (phytohemagglutinin and lipopolysaccharide, respectively). The intermediate phase was marked by productive virus replication in the salivary gland, injury to lymphoid elements, a depressed response of splenocytes to mitogens (phytohemagglutinin and lipopolysaccharide), and decreased humoral splenocytes to phytohemagglutinin stimulation was again increased, and a nonproductive latent infection was established. Study by scanning electron microscopy of splenocytes during the course of infection revealed morphological changes which were correlated with functional alterations. PMID- 6266967 TI - Polymyxin B inactivation of lipopolysaccharide in vaccines of Gram-negative bacteria. AB - Endotoxin activity in suspensions of Bordetella pertussis, Escherichia coli, Haemophilus influenzae, and Pseudomonas aeruginosa was often markedly decreased by polymyxin B. Polymyxin B treatment may be a means to reduce inflammatory reactivity of lipopolysaccharide in vaccines of gram-negative bacteria. PMID- 6266968 TI - Restriction endonuclease map of phage group 2 Staphylococcus aureus exfoliative toxin plasmid. AB - A restriction endonuclease map of the phage group 2 Staphylococcus aureus exfoliative toxin plasmid pRW001 was constructed. The orientation of the restriction endonuclease fragments was determined by a series of single and double enzyme digestions. The location of the deletions found in pRW002, a naturally occurring deletion mutant of the exfoliative toxin plasmid, was determined by comparing the restriction endonuclease fingerprints of the two plasmids. This physical map provided a means for comparing other insertion or deletion mutants of the exfoliative toxin plasmid. PMID- 6266969 TI - Metabolic requirements for rabbit polymorphonuclear leucocyte lipoxygenase activity. AB - Lipoxygenase product formation by rabbit PMNs on exposure to the divalent ionophore A23187 was dependent upon pH, metabolic energy and substrate availability. Formation of 5-HETE and 5,12-diHETE (the major arachidonate oxygenation products) was inhibited by calcium depletion, by the metabolic inhibitors iodoacetate and 2-deoxyglucose, and by the substrate inhibitor TYA. The reaction had a pH optimum of 7.0-7.5. Colchicine, cytochalasin B and isoprenaline had no significant effects on HETE formation. PMID- 6266971 TI - Heavy metal modulation of lymphocyte activities--II. Lead, an in vitro mediator of B-cell activation. AB - Investigation of the immunopotentiating effect(s) of Pb2+ on the humoral immune response has provided evidence that a heavy metal can alter the proliferation and differentiation of B-cells. Pb2+ interacted with B-cells to enhance both their proliferation and their differentiation into sheep red blood cell (SRBC)-specific PFC. Preincubation of B-cells with Pb2+ for only 1 h enhanced their activities. Enhancement of in vitro humoral immunity to SRBC was due to direct Pb2+ activation of B-cells and enhancement of T-cell help. Furthermore, Pb2+ and the cyclic nucleotides dibutyryl cyclic adenosine monophosphate (DBcAMP) or cyclic guanosine monophosphate (cGMP) worked in a synergistic manner to enhance the B cell proliferation, and Pb2+ and DBcAMP synergistically enhanced PFC development. Ni2+, which had been shown to enhance PFC development in cultures of spleen cells in a manner equivalent to Pb2+, did not enhance PFC development in B-cell cultures as well as Pb2+ and did not produce synergistic effects with DBcAMP or cGMP. The possible mechanisms by which Pb2+ enhances B-cell activities and the implications of these effects are discussed. PMID- 6266970 TI - Prevention of peroxidase mediated inhibition of neutrophil motility and lymphocyte transformation by levamisole, OMPI, sodium aurothiomalate, indomethacin and tolmetin in vitro. AB - The effects of sodium aurothiomalate, levamisole, its active metabolite OMPI and the anti-inflammatory agents indomethacin and tolmetin on neutrophil motility and post-phagocytic hexose monophosphate shunt activity, superoxide and H2O2 generation and myeloperoxidase (MPO) mediated iodination of Candida albicans were investigated in vitro. All five agents caused stimulation of neutrophil random motility and migration towards the leucoattractants f-met-met-phe and EAS. Only levamisole caused inhibition of H2O2 and superoxide production, which was associated with inhibition of HMS activity and not related to superoxide scavenging activity. All five agents caused inhibition of MPO mediated iodination of C. albicans. The relationship between inhibition of peroxidase mediated iodination and enhanced motility was further investigated using the horseradish peroxidase (HRP) H2O2/iodide system. Incubation of neutrophils with this system caused inhibition of neutrophil motility. However in the presence of the various drugs neutrophils were protected from inhibition of motility by the HRP/H2O2/iodide system. Further experiments showed that lymphocyte transformation to mitogens was also inhibited by the HRP/H2O2/iodide system. Incubation of lymphocytes with the various drugs prior to exposure to HRP/H2O2/iodide protected the lymphocyte mitogenic responsiveness. PMID- 6266972 TI - Water radiolysis products and nucleotide damage in gamma-irradiated DNA. AB - The radiation chemistry of nucleotide damage introduction into DNA gamma irradiated in dilute aqueous solution has been studied with a damage-specific DNA binding protein. Irradiation in air, N2 or N2O in the presence and absence of free radical scavengers revealed that protein-recognizable lesions were introduced both by the hydrated electron and by the combination of the hydroxyl radical and superoxide anion radical, but not by the hydroxyl radical alone. In addition, nucleotide damage was introduced into DNA by an enzymatic superoxide generating system. PMID- 6266973 TI - Physiological evidence (hypothermia) for central effects of beta-blocker agents. AB - In recent studies carried out during the last decade, it has been found that beta blocker agents have many central effects. These findings raise the question how beta-blocker agents act when they influence central effects. In spite of intensive research efforts on this subject, no answer has been offered so far. Several studies indicate that the effect of beta-blocker agents on the dopaminergic receptors in the brain is very similar to their effect on beta adrenergic receptors. In a set of experiments we checked the effect of two beta blocker agents: oxprenolol and dl-propranolol, and the effect of d-propranolol on hypothermia induced by d-amphetamine and apomorphine at an ambient temperature of 4 degrees C. It was found that the two beta-blockers and the d-propranolol significantly potentiated the effect of hypothermia induced by d-amphetamine and apomorphine, an effect which is mediated by the central dopaminergic system. However, the activity of the beta-blockers was agonistic. Furthermore, the influence of d-propranolol on hypothermia shows that this dopaminergic agonistic activity of the beta-blockers is not related to peripheral or central beta receptor blockage. PMID- 6266974 TI - Reflex control and modulation of ACTH and corticosteroids. PMID- 6266975 TI - Direct cannulation and injection lymphangiography of the canine cardiac and pulmonary efferent mediastinal lymphatics in experimental congestive heart failure. AB - Lymphangiograms were made in dogs with experimental congestive heart failure by cannulation of the left cardiac efferent (LCE), left pulmonary efferent (LPE), or cardiopulmonary lymphatic and injection of radiopaque medium. The lymphoangiograms showed cardiac enlargement and dilated mediastinal lymphatic channels consistent with an increase in lymph flow. By consecutive injections in the LCE and LPE, wer demonstrated that a common channel, the cardiopulmonary lymphatic, is opacified by injection in either the LPE or LCE. This common channel has been called the "cardiac lymphatic" and used for the collection of "cardiac" lymph. The authors' experiments suggest that this cardiopulmonary lymphatic carries both cardiac and pulmonary lymph. PMID- 6266976 TI - Enzyme activities of the lipid metabolism in subcellular fractions of the hypertrophying heart during adaptation to hypoxia. PMID- 6266977 TI - Electron microscopic studies in lipid storage disease. AB - Biopsy and autopsy specimens from patients with Gaucher's disease and Niemann Pick disease were studied ultrastructurally. The morphological features were compared with those obtained from paraffin-embedded tissues after reprocessing the tissue for electron microscopy. With routine glutaraldehyde-osmium fixation, both surgical and autopsy specimens from Gaucher's disease showed cytoplasmic bodies containing elongated tubular structures with a translucent appearance. Tissue processed from paraffin-embedded blocks showed moderate preservation of the cytoplasmic glucocerebroside-containing bodies in Gaucher's disease. Routine fixation for electron microscopy of surgical of surgical and autopsy specimens from Niemann-Pick disease showed characteristic cytoplasmic vacuolated formations which were frequently multilaminated. These sphingomyelin-containing vacuoles were poorly preserved in tissue reprocessed from paraffin blocks. PMID- 6266978 TI - New oil-contrast media for small vessel lymphography. PMID- 6266980 TI - "In situ" determinations of apparent Km and Vmax of brush border disaccharidases along the villi of normal human jejunal biopsy specimens. A quantitative histochemical study. AB - In order to characterize lactase/beta-glucosidase and the neutral alpha glucosidase kinetically in the brush border membrane at different villus sites of normal human jejunal mucosa, a quantitative histochemical study has been carried out on biopsy specimens of patients only suffering from functional disturbances revealing normal mucosal architecture. The apparent Vmax-values of both alpha- and beta-glucosidases increased significantly from the villus base to the transition zone between medium and apical villus third. During enterocyte maturation on the villus no changes in the apparent Km-values could be detected. Equally the ratios between the Vmax-values of the disaccharidases remained constant. Male persons exhibited significantly greater apparent Vmax-values for alpha-glucosidase than females at both villus measuring positions. The findings can be taken as a starting point for the evaluation of local changes of apparent enzyme-kinetic data under pathological conditions. PMID- 6266979 TI - [Multiple glomus tumors]. AB - Two patients with disseminated glomus tumors (glomangiomas) are reported. Histologically, the angiomatous from typical of multiple glomus tumors was found. Th glomus tumors are related to the arterio-venous anastomoses (organ of Hoyer Grosser). The most important histological variants are the epithelioid and the angiomatous type. Possibly, the former is related to the arterial segment, the latter to the venous segment of the normal arterio-venous anastomoses. The histological identification of glomus cells is diagnostic. The nature of these cells has been under discussion since Masson's time. Ultrastructurally, they have been clearly identified as modified smooth muscles cells. Electron-microscopy can be helpful in the differentiation of glomus tumors from hemangiopericytomas which may sometimes be difficult histologically. PMID- 6266981 TI - [Distribution of some hydrolases in the rat kidney (author's transl)]. AB - Most of the available histochemical methods and techniques (azodye, metal salt and indigogenic methods, cryostat, free-floating and lyophilized section techniques) and different modifications of these methods (different substrate concentrations, pH, temperature, incubation time e.g.) were applied to study the distribution of acid phosphatase (AcPB = after Barka and Anderson; AcPG = after Gomori), beta-glucuronidase (beta-Glu), aryl sulfatase (AS), beta-N acetylglucosaminidase (NAG), acid 5'-nucleotidase (a5-Nucl), non-specific esterase (NE) and alkaline phosphatase (AlP) in the kidneys of rats of both sexes. The optimal conditions for the demonstration of these enzymes were established. As most important proved: the incubation of free-floating sections cut from "standard"-fixed (2 h in formol-calcium continued for another 18-22 h in the same fixative plus 0.88 M sucrose at 4 degrees C) kidney slices - only for AcPB and NE material fixed after Holt had to be used; the incubation for AlP and NE at 4 degrees C; final pH of the incubation medium for AcPB 5.5, AcPG 5.0 and NE 6.5; the use of Fast Garnet GBC Salt as coupler in the NE azo-dye reaction. Sex differences and for the female rats an increased activity during oestrus were established for all hydrolases studied. In particular the following results were obtained: AcPB, a5-Nucl and A1P are more intensive in male and AcPG in female S1 segments of the juxtamedullary nephrons in relation to the nephrons of the other parts of the cortex. In the medullary rays the NE and the a5-Nucl show a higher activity in the S2 segments of female rats demonstrate a more intensive activity for NAG and NE. This is true for AcPG and A1P in male rats. In the inner medulla a stronger beta-Glu activity in male rats and a stronger NAG activity in female rats is observed. The AcPB activity of the cortical distal tubules is higher in male rats. PMID- 6266983 TI - Late onset 21-hydroxylase deficiency and HLA in the Ashkenazi population: a new allele at the 21-hydroxylase locus. PMID- 6266982 TI - The use of a hidden metal-capture reagent for the measurement of Na+--K+-ATPase activity: a new concept in cytochemistry. AB - The original lead-trapping method for demonstrating Na+--K+-ATPase activity was discredited because of the effect that lead ions can have on the substrate and on the enzyme. Current methods, that measure this activity by the related K+ dependent phosphatase activity, do not appear to measure activity that is known, from microchemistry, to occur in proximal convoluted tubules. The disadvantages of using lead appear to have been overcome by the use of a new reagent in which the lead is complexed with ammonium citrate ions; phosphate, liberated enzymatically, successfully competes with these ions. The activities of total ATPase and of the ouabain sensitive Na+--K+-ATPase have been measured in three regions of the nephron in the guinea-pig and in the rat. The relative activities found, by this method, in the different regions of the latter, appear to be comparable with results found by others, using microchemical methods applied to isolated regions of the nephron. PMID- 6266984 TI - Quantitative analysis of cell surface HLA structures by means of monoclonal antibodies. AB - Quantitative data on the binding of murine monoclonal antibodies ot whole human lymphoblastoid lines and peripheral blood lymphocytes (PBL) are reported. Antibodies reacting with beta 2m or a common part of the HLA heavy chains and nonpolymorphic determinants of the DR dimer were used. The equilibrium constant (K) of the reaction and the total number of antigenic determinants was graphically estimated. For the above-mentioned antibodies, K ranged between 5 X 10(8) and 4 C 10(9) l/mole at 0 degrees C and progressively decreased with the increasing temperature. T cells expressed less HLA and beta 2M determinants than the B cells. The number of determinants per surface unit is higher on the B cell from PBL than on E.B. virus-transformed cell lines and is generally very low, suggesting that the complement-dependent cytotoxic activity is a phenomenon depending on membrane fluidity. A portion of beta 2m seems not to be bound to the HLA heavy chains on B cells as well as on T line surface, as already shown for Molt 4 line. PMID- 6266985 TI - Intra-HLA recombinations localizing the 21-hydroxylase deficiency gene within the HLA complex. AB - Close linkage between HLA and the gene for 21-OH deficiency causing congenital virilizing adrenal hyperplasia (CVAH) has been well documented. HLA-A/B and HLA/GLO recombination data placed the CVAH gene within the HLA-A to GLO interval, with CVAH invariably segregating with HLA. HLA-A,B,C,DR and GLO typing and ACTH stimulation to determine carrier status was done on seven families. Carrier status correlated with the appropriate HLA haplotypes in all offspring, with two exceptions. Two intra-HLA recombinants were detected in one three-generation family. The father of the proband is homozygous for HLA-A2,Cw2,B27 but is a DR2/DR4 heterozygote. The CVAH gene segregated with DR2 in all but one of his offspring who is a carrier and is DR4. This finding is consistent with recombination between the CVAH gene and DR. Study of the father's family confirmed synteny of the CVAH gene and DR2. Three of four sibs of the father inherited this haplotype and were CVAH carrier, as was the paternal grandmother, whose other haplotype was A1, Bw44,DR1. One of the father's sibs was shown serologically to be a HLA-B/D maternal recombinant and a noncarrier. she inherited the A1,Bw44 of one maternal haplotype, but the DR2 of the other. In both recombinants in this family the CVAH gene segregated with the A to B interval, separate from D. While we cannot determine whether the CVAH gene is in the HLA-A to B or B to D interval, this is the first report of two intra-HLA recombinations in one family that unequivocally map the CVAH gene inside HLA-D. PMID- 6266987 TI - Seroepidemiologic aspects of cytomegalovirus infection in a general hospital pediatric population: a pilot study. PMID- 6266986 TI - Presentation of viral antigens by human vascular endothelial cells in vitro. AB - Endothelial cells (EC) separated from the umbilical vein were shown to be free of contaminating monocytes. EC could replace peripheral blood-derived macrophages as antigen-presenting cells for in vivo sensitized T cells towards a variety of viral antigens. The T-cell--CE-antigen response was also specificity inhibited by anti-HLA-DR antisera. T cells primed by antigen together with autologous macrophages could be restimulated by antigen pulsed HLA-D/DR identical EC in an antigen specific secondary response, indicating a similar mechanism for antigen presentation by EC or macrophages. PMID- 6266989 TI - Twelve years' experience with irradiation as the primary treatment for breast cancer. PMID- 6266988 TI - Follow-up neurological evaluation in patients with small cell lung carcinoma treated with prophylactic cranial irradiation and chemotherapy. PMID- 6266990 TI - The place of radiotherapy in the treatment of synovial sarcoma. PMID- 6266991 TI - Effect of naloxone on ventilation in newborn rabbits. AB - Endorphins have been isolated from amniotic fluid and cord blood of mammals. To determine if these agents influence ventilation after birth, we measured ventilation (VE), tidal volume, inspiratory time, and respiratory frequency (f) in 19 rabbit pups before and after administration of naloxone (NLX), an endorphin antagonist. Tracheostomy and carotid artery cannulation were performed under light ether anesthesia. After 30-90 min for recovery the pups were placed in a body plethysmograph. Rectal temperature was kept at 37 +/- 0.5 degrees C. After 15 min of control measurements we infused saline, which had no respiratory effect. NLX (4 microgram/g) was then infused and measurements continued for 30 min. In 6 of 7 pups less than or equal to 4 days old, VE increased to 140-180% of control values and remained elevated for the remainder of the study period. Increased VE was due solely to increased f. By contrast, only 1 of 12 pups greater than or equal to 5 days old responded in this fashion. This difference was significant (P less than 0.005). Arterial blood gases were measured before and after NLX in 10 pups. In those pups who increased their ventilation after NLX, arterial CO2 tension fell and pH rose above pre-NLX values (P less than 0.05) for both variables). Blood gases of the group whose ventilation was uneffected remained unchanged. These results indicate that early in postnatal life endorphins probably modulate central respiratory drive in rabbits but that these agents become less important with maturation. PMID- 6266992 TI - Contribution of environmental factors in development of hyperbaric bradycardia. AB - Bradycardia has been observed in animals and humans upon exposure to various hyperbaric environments. However, the relative contribution of ambient pressure, gas density, inert gas species, and inspired O2 tension has not been defined. By means of cutaneous ECG leads, the heart rates of unanesthetized rats were recorded and compared in 11 separate thermo-neutral environments. Ambient pressures applied were 1, 3, and 10 ATA, O2 partial pressure PO2 ranged from 140 to 1,590 Torr, and gas densities were varied from 0.40 to 11.45 g/l, utilizing either N2-O2 or He-O2 mixtures. The exposure heart rates were averaged over a 30 min period and compared with a preceding control value obtained in 1 ATA normoxic He or N2. Significant bradycardia was associated with hyperoxia in environments containing either He or N2, with a magnitude proportional to log PO2. On the other hand, under normoxic conditions bradycardia was not observed despite the similar density, pressure, and inert gas components. It is concluded that hyperoxia is the most important variable of those considered in the development of hyperbaric bradycardia. PMID- 6266994 TI - Effects of 100% O2 breathing on permeability of alveolar epithelium to solute. AB - We measured the effects of 100% O2 exposure at 1 atm for 48 (n = 5) and 63 h (n = 6) on the solute permeability of the alveolar epithelium of rabbits. We instilled 10-15 ml of saline containing trace amounts of 131I-albumin (r approximately 35 A), 125I-cytochrome c (r approximately 17 A), and [57Co]cyanocobalamin (r approximately 6.5 A) into an atelectatic segment of the right lower lobe. Egress of these tracers was determined from their change in concentration in the alveolar saline and their detection in arterial blood. All tracers left the alveolar space and appeared in the arterial blood on the 63-h O2 group, cytochrome c and cyanocobalamin in the 48-h O2 group, and only cyanocobalamin in the control (air breathing). The O2-exposed animals had PaO2 values higher than 500 Torr, normal PaCO2 and pH, and wet-to-dry lung weight ratios not different from control. We concluded that increasing the length of O2 exposure increases the solute permeability of the alveolar epithelium and this precedes the appearance of pulmonary edema. PMID- 6266993 TI - Release of oxygen products from lung macrophages by N-formyl peptides. AB - Incubation of guinea pig pulmonary macrophages with N formylmethionylphenylalanine (FMP) resulted in 1) a rapid increase in O2 consumption and 2) an accumulation of superoxide anion and hydrogen peroxide in the extracellular medium. The accumulation of superoxide anion and hydrogen peroxide was completely prevented in the presence of superoxide dismutase and catalase, respectively. FMP-stimulated O2 consumption and superoxide anion and hydrogen peroxide accumulation were proportional to the macrophage concentration, showed similar dependence on FMP concentration, had nearly identical kinetics, and were partially abolished by antimycin A, an inhibitor of mitochondrial respiration. FMP also stimulated a three- to fourfold increase in hexose monophosphate shunt (HMS) activity. Catalase had no effect on the amount of glucose oxidized by the HMS, indicating that removal of hydrogen peroxide was without effect on the observed HMS activity. Since FMP is similar in structure to the oligopeptides of bacterial metabolism, its ability to stimulate the release of these microbiocidal products of oxygen metabolism may be important in vivo. PMID- 6266996 TI - Components of alveolar-arterial O2 gradient during rest and exercise at sea level and high altitude. AB - To determine the effects of exercise and high altitude on the contributions of shunt, ventilation-perfusion (V/Q) nonhomogeneity, and diffusion limitation to the alveolar-arterial O2 gradient (AaDo2), we measured pulmonary exchange of O2, CO2, and six inert gases (SF6, ethane, cyclopropane, halothane, diethyl ether, and acetone) during rest and exercise in unanesthetized dogs at sea level and after acute exposure to an altitude of 6,096 m in a hypobaric chamber. Shunt and dead-space fractions, calculated from inert gas measurements, did not change. High altitude decreased the inert gas partial pressure gradients between mixed alveolar gas and mixed end-capillary blood, indicating that V/Q relationships became more homogeneous. Exercise had no effect on these gradients. At sea level, AaDo2 was mainly due to V/Q nonhomogeneity, with a small portion due to shunt. At high altitude, the contribution of shunt became negligible and that of V/Q nonhomogeneity diminished. These improvements were partially offset, however, by a gradient due to diffusion limitation. Exercise had no effect on AaDo2 or any of its components. At high altitude, estimated pulmonary O2 diffusing capacity averaged 20.8 ml.min-1 at rest and 35.3 ml-min-1.Torr-1 during exercise. PMID- 6266995 TI - Dependence of carotid chemoreceptor stimulation by metabolic agents on PaO2 and PaCO2. PMID- 6266997 TI - Temporal changes in effectiveness of a constant inspiratory-terminating vagal stimulus. AB - When an electrical stimulus is applied to the cervical vagus during inspiration it results in earlier termination of that phase. We investigated the temporal behavior of the effect of such a stimulus in the interval between its application and inspiratory termination to gain insight into the central processing of these signals. In pentobarbital-anesthetized cats we determined the threshold for inspiratory termination by delivering stimulus trains of constant duration to one vagus nerve at different times after inspiratory onset. The threshold frequency was obtained when the other nerve was unstimulated and when it was stimulated using trains of constant frequency (conditioning stimulus) beginning soon after inspiratory onset. The difference in threshold between the two test indicated the effectiveness of the conditioning stimulus in reducing threshold for inspiratory termination. The effectiveness of the conditioning stimulus increased progressively, reached a peak value at approximately 0.8 s, and progressively declined thereafter. This behavior indicates substantial integrative and accommodative processing of inspiratory terminating vagal inputs. PMID- 6266998 TI - Control of release of surfactant phospholipids in the isolated perfused rat lung. AB - We used the isolated rat lung to investigate surfactant release. The lung was ventilated at 60.min-1 with 5% CO2-95% O2 and perfused at 10 ml.min-1 with Krebs bicarbonate (4.5% albumin). After 20 min during which antagonist drugs were present, the lungs were either hyperventilated or agonist drugs were added. After another 15 min lungs were lavaged. Peak inspired pressures (PIP) in excess of 12 cmH2O produced progressively greater phospholipid (PL) yields. Whereas ventilating with PIP of 9 cmH2O and end-expired pressure(EEP) of 5 cmH2O produced 5.9 +/- 0.8 (mean +/-SD) (n = 17) mg PL. g dry lung-1, ventilating with PIP of 20 cmH2O and EEP of 0 cmH2O produced 10.1 +/- 1.3 (n = 26). PL release was unaffected by tetrodotoxin, propranolol, atropine, cyproheptadine, or indomethacin. PL was increased by salbutamol and dibutyryl adenosine 3',5'-cyclic monophosphate but not by pilocarpine or dibutyryl guanosine 3',5'-cyclic monophosphate. We conclude, that increasing tidal volume immediately releases surfactant, probably by distorting the type II cell and elevating cAMP. An intrapulmonary neural reflex is not involved in this response of the isolated rat lung, nor is histamine, 5-hydroxytryptamine, or a prostaglandin. PMID- 6266999 TI - Evidence for a sodium electrogenic pump in airway smooth muscle. AB - We tested the hypothesis that the resting membrane potential (Em) of guinea pig and bovine airway smooth muscle (ASM) (m. trachealis transversus) might be influenced by a Na+ electrogenic pump. To determine the Em of ASM, glass microelectrodes filled with 3 M KCI and offering an impedance between 40 and 80 M omega were used. After incubation a normal oxygenated physiological salt solution (PSS) [pH, 7.38 +/- 0.02 (SD); temp, 37 +/- 0.5 degrees C (SD)] for 60 min, the Em of guinea pig ASM was -62.5 +/- 1.25 (SE) mV (successful impalement of 437 cells of 37 tracheal preparations from 37 different animals) and that of bovine ASM was -60.0 +/- 1.5 mV (successful impalement of 306 cells of 26 tracheal preparations from 26 different animals). Tracheal preparation consisted of 10-mm long segments of cervical or intrathoracic portions of the trachea. Approximately 30% of the cells of both species exhibited spontaneous electrical activity (slow waves). Studies to determine whether an electrogenic pump was present revealed that a) ouabain (10(-5) M), a specific inhibitor of the Na+ pump, causes depolarization of ASM in both species; b) exposure of ASM to a K+-free solution resulted in a similar depolarization followed by a hyperpolarization; c) exposure to normal PSS after "Na+ loading" resulted in significant hyperpolarization of ASM when these preparations were returned to normal PSS; and d) Em of ASM decreased on exposure to a low temperature (21, 25, and 29 degrees C) and increased at a high temperature (40 degrees C). It is concluded that an active electrogenic pump is present in guinea pig and bovine airway smooth muscle. PMID- 6267000 TI - Atypical hypoadrenocorticism in three dogs. AB - Three dogs with hypoadrenocorticism did not have characteristically abnormal serum concentrations of sodium, potassium, and chloride and had not been treated with glucocorticoids. Diagnosis was based on lack of adrenocortical response to exogenous adrenocorticotropic hormone. Clinical signs included lethargy, weakness, anorexia, vomiting, and weight loss. The case demonstrated that the diagnosis of canine hypoadrenocorticism should not be excluded on the basis of normal serum electrolyte values. PMID- 6267001 TI - Glutamate and aspartate: alteration of thresholds and response patterns of auditory neurons. AB - Iontophoretic application of the excitant amino acids glutamate and aspartate onto neurons in the chinchilla cochlear nucleus results in a lowering of the threshold of response to auditory stimuli. Neurons that display 'on'-type phasic responses to toneburst stimuli may become tonic, sustained responders with iontophoretic application of glutamate or aspartate. The ability of either glutamate or aspartate to effect changes in thresholds and response patterns of cochlear nucleus neurons is further evidence that one of these amino acids may be the afferent transmitter of the auditory nerve. The effects seen with these excitant amino acids may also provide insight into the underlying synaptic events involved in the generation of a particular response pattern. PMID- 6267002 TI - Cortisol and luteinizing hormone after adrenocorticotropic hormone administration to postpartum beef cows. AB - Cortisol and luteinizing hormone (LH) were measured in serum after the administration of adrenocorticotropic hormone (ACTH) to suckled (S) and nonsuckled (NS) beef cows. Blood was sampled on 2 consecutive days every 2 weeks for four bleeding periods starting 14 days after calving. Cows were injected with 200 IU ACTH or saline in a 2-day switchback design. Serum was collected before ACTH or saline injection and at 30-min intervals thereafter for 8 hours. Average cortisol concentrations in serum were similar in S and NS cows (6.4 +/- .6 and 6.1 +/- .8 ng/ml, respectively) after saline. Average cortisol concentrations in serum collected during an 8-hr period after ACTH on days 14, 28, 42 and 56 postpartum were 24.7 +/- 2.4, 31.8 +/- 3.5, 36.4 +/- 4.2 and 40.7 +/- .5 ng/ml, respectively, for S cows, and 31.1 +/- 2.9, 44.7 +/- 5.2, 45.0 +/- 5.7 and 46.0 +/- 5.4 ng/ml, respectively, for NS cows. Cortisol response to ACTH, measured as area under the response curve, was greater (P less than .05) in NS than in S cows. Amount of cortisol released by 200 IU ACTH was maximal by days 28 to 29 postpartum in NS cows, but the response increased gradually between days 14 to 15 and days 56 to 57 in S cows. overall, LH in serum averaged .55 +/- .08 ng/ml for S cows and .92 +/- .06 ng/ml for NS cows after saline, and .49 +/- .07 ng/ml for S cows and .94 +/- .06 ng/ml for NS cows after ACth. Although mean and peak serum LH concentrations did not differ between cows given ACTH and those given saline, the number of LH peaks and the number of cows having LH after saline. Mean serum LH concentrations were lower (P less than. 05) in S than in NS cows at 28 days postpartum. The number of LH peaks was lower (P less than .05) and the magnitude of the largest LH peak tended to be lower (P less than .06) in S cows at all sampling periods. PMID- 6267003 TI - Monensin supplementation and in vivo methane production by steers. AB - The effect of monensin on methanogenesis was examined. Growing steers were fed 4.1 kg daily of a low roughage diet (12.6% crude protein, 12% acid detergent fiber) or 5.4 kg daily of either a medium roughage (12.3% crude protein, 27% acid detergent fiber) or a high roughage diet (14.4% crude protein, 40% acid detergent fiber) with or without 200 mg of supplemental monensin. At the low and high roughage levels, monensin increased (P less than .05) the molar proportion of ruminal propionate and decreased acetate. Methane production and inhibition by monensin declined with time postprandially. Monensin decreased methane production by 16% (P less than .05) at the two lower roughage levels and 24% (P less than .01) at the high roughage level. Total heat production and respiratory quotient remained unaltered by monensin. Averaged across roughage levels, metabolizable energy was increased (P less than .01) 5.2% by monensin. Although dry matter digestibility and N retention were not statistically altered, both tended to increase with monensin. Reduced ruminal methane production with monensin feeding can explain a portion of the increased feed efficiency. PMID- 6267004 TI - [Leprosy in northern India. IV. Chief complaints and clinical features of lepromatous cases (author's transl)]. PMID- 6267005 TI - 6-beta-bromo- and 6-beta-iodo penicillanic acid, two novel beta-lactamase inhibitors. PMID- 6267006 TI - Identification of the tetracycline resistance promoter and repressor in transposon Tn10. AB - The structural and regulatory functions encoding tetracycline resistance in transposon Tn10 lie within a 2,700-base pair region. Using recombinant plasmids with different deoxyribonucleic acid sequences adjacent to a HincII site in this region, we located the promoter controlling the expression of tetracycline resistance. These various sequences conferred altered levels of tetracycline resistance. Plasmids containing deletions of a 695-base pair HincII fragment were constitutive and showed the loss of a 23,000-dalton tetracycline-inducible polypeptide, thus identifying the repressor and the location of its gene. PMID- 6267007 TI - Localization of an amikacin 3'-phosphotransferase in Escherichia coli. AB - A plasmid-encoded enzyme reported by us to phosphorylate amikacin in a laboratory strain of Escherichia coli has been localized in the bacterial cell. More than 88% of this amikacin phosphotransferase (APH) activity was retained in spheroplasts formed by ethylenediaminetetraacetate-lysozyme treatment of an APH containing E. coli transconguant known to form spheroplasts readily. By comparison, the spheroplasts retained 94% of deoxyribonucleic acid polymerase I and 98% of glutamyl-transfer ribonucleic acid synthetase, two internal markers, whereas less than 10% of the activity of a periplasmic marker, acid phosphatase, was present in spheroplasts. Treatment of whole cells of the transconjugant with chemical probes incapable of crossing the plasma membrane obliterated acid phosphatase activity, whereas the internal markers deoxyribonucleic acid polymerase I, glutamyl-transfer ribonucleic acid synthetase, and beta galactosidase were virtually unaffected after treatment for 5 min; more than 60% of the APH activity remained. As a control, similar chemical treatment of sonic extracts, in which enzymes were not protected by bacterial compartmentalization, produced more extensive reduction in the activities of all test enzymes, including APH. Spheroplasts preincubated with adenosine triphosphatase were shown by thin-layer chromatography to phosphorylate amikacin. Spheroplasts of cells grown in the presence of H(3) (32)PO(4) were shown to utilize internally generated adenosine 5'-triphosphate in the phosphorylation of amikacin. The absence of (32)P-phosphorylated amikacin after incubation of [gamma (32)P]adenosine 5'-triphosphate with spheroplasts confirmed that exogenous adenosine 5'-triphosphate was not used in the reaction. These results suggest an internal location for APH. This conclusion has implications for the role of such enzymes in aminoglycoside resistance of gram-negative bacteria. PMID- 6267008 TI - Defective enzyme II-BGlc of the phosphoenolpyruvate:sugar phosphotransferase system leading to uncoupling of transport and phosphorylation in Salmonella typhimurium. AB - Transport and phosphorylation of glucose via enzymes II-A/II-B and II-BGlc of the phosphoenolpyruvate:sugar phosphotransferase system are tightly coupled in Salmonella typhimurium. Mutant strains (pts) that lack the phosphorylating proteins of this system, enzyme I and HPr, are unable to transport or to grow on glucose. From ptsHI deletion strains of S. typhimurium, mutants were isolated that regained growth on and transport of glucose. Several lines of evidence suggest that these Glc+ mutants have an altered enzyme II-BGlc as follows. (i) Insertion of a ptsG::Tn10 mutation (resulting in a defective II-BGlc) abolished growth on and transport of glucose in these Glc+ strains. Introduction of a ptsM mutation, on the other hand, which abolishes II-A/II-B activity, had no effect. (ii) Methyl alpha-glucoside transport and phosphorylation (specific for II-BGlc) was lowered or absent in ptsH+,I+ transductants of these Glc+ strains. Transport and phosphorylation of other phosphoenolpyurate:sugar phosphotransferase system sugars were normal. (iii) Membranes isolated from these Glc+ mutants were unable to catalyze transphosphorylation of methyl alpha-glucoside by glucose 6 phosphate, but transphosphorylation of mannose by glucose 6-phosphate was normal. (iv) The mutation was in the ptsG gene or closely linked to it. We conclude that the altered enzyme II-BGlc has acquired the capacity to transport glucose in the absence of phosphoenolpyruvate:sugar phosphotransferase system-mediated phosphorylation. However, the affinity for glucose decreased at least 1,000-fold as compared to the wild-type strain. At the same time the mutated enzyme II-BGlc lost the ability to catalyze the phosphorylation of its substrates via IIIGlc. PMID- 6267009 TI - Physical map of the Salmonella typhimurium histidine transport operon: correlation with the genetic map. AB - A detailed restriction map of a 12.4-kilobase EcoRI fragment of Salmonella typhimurium deoxyribonucleic acid (DNA) containing the entire histidine transport operon and the argT gene is presented. Subclones of specific regions of the transport operon of S. typhimurium were constructed in plasmid vectors. An accurate correlation between the restriction map and the location of genetically defined deletions was obtained by hybridizing restriction digests of chromosomal DNA from strains carrying each deletion with cloned transport operon DNA as a probe. These data were used to position the histidine transport genes on the cloned 12.4-kilobase fragment of DNA. PMID- 6267010 TI - Cyclic adenosine 3',5'-monophosphate-mediated hyperinduction of araBAD and lacZYA expression in a crp mutant of Escherichia coli K-12. AB - A spontaneous lac+ revertant of an adenylate cyclase deletion strain of Escherichia coli K-12 was isolated and characterized. This revertant, designated strain KC20, exhibited a pleiotropic suppression of the adenylate cyclase defect, with the crp locus being the site of the suppressor mutation. Cyclic adenosine 3',5'-monophosphate at an exogenous concentration of 1 mM severely inhibited the growth of strain KC20 in minimal media. Lower concentrations of the cyclic nucleotide elicited less pronounced effects. Studies on araBAD and lacZYA expression showed that cyclic adenosine 3',5'-monophosphate elicited an initial dose-dependent hyperinduction of these systems. Hyperinduction of araBAD, in L arabinose grown cultures of strain KC20, resulted in accumulation of inhibitory concentrations of methylglyoxal. Hyperinduction of lacZYA in lactose-grown cultures of strain KC20 did not result in any such methylglyoxal production. PMID- 6267011 TI - Characterization of a membrane-associated cytidine diphosphate-diacylglycerol dependent phosphatidylserine synthase in bacilli. AB - The synthesis of phosphatidylserine in two gram-positive aerobic bacteria has been partially characterized. We have located a cytidine 5'-diphospho diacylglycerol:L-serine O-phosphatidyltransferase (phosphatidylserine synthase) activity in the membrane fraction of Bacillus licheniformis and Bacillus subtilis. The activity was demonstrated to be membrane associated by differential centrifugation, sucrose gradient centrifugation, and detergent solubilization. The direct involvement of cytidine 5'-diphospho-diacylglycerol in the reaction was demonstrated by the conversion of the liponucleotide phosphatidyl moiety to phosphatidylserine. This activity is dependent on divalent metal ion (manganese being optimal) and is stimulated by nonionic detergent and its product phosphatidylserine. Based on studies with various combinations of products and substrates, the reaction appears to follow a sequential BiBi kinetic mechanism. PMID- 6267012 TI - Uptake and metabolism of sucrose by Streptococcus lactis. AB - Transport and metabolism of sucrose in Streptococcus lactis K1 have been examined. Starved cells of S. lactis K1 grown previously on sucrose accumulated [14C]sucrose by a phosphoenolpyruvate-dependent phosphotransferase system (PTS) (sucrose-PTS; Km, 22 microM; Vmax, 191 mumol transported min-1 g of dry weight of cells-1). The product of group translocation was sucrose 6-phosphate (6-O phosphoryl-D-glucopyranosyl-1-alpha-beta-2-D-fructofuranoside). A specific sucrose 6-phosphate hydrolase was identified which cleaved the disaccharide phosphate (Km, 0.10 mM) to glucose 6-phosphate and fructose. The enzyme did not cleave sucrose 6'-phosphate(D-glucopyranosyl-1-alpha-beta-2-D-fructofuranoside-6' phosphate). Extracts prepared from sucrose-grown cells also contained an ATP dependent mannofructokinase which catalyzed the conversion of fructose to fructose 6-phosphate (Km, 0.33 mM). The sucrose-PTS and sucrose 6-phosphate hydrolase activities were coordinately induced during growth on sucrose. Mannofructokinase appeared to be regulated independently of the sucrose-PTS and sucrose 6-phosphate hydrolase, since expression also occurred when S. lactis K1 was grown on non-PTS sugars. Expression of the mannofructokinase may be negatively regulated by a component (or a derivative) of the PTS. PMID- 6267013 TI - Cloning of genes involved in membrane lipid synthesis: effects of amplification of phosphatidylglycerophosphate synthase in Escherichia coli. AB - The structural gene (pgsA) for the CDP-diacylglycerol:sn-glycero-3-phosphate phosphatidyltransferase (EC 2.7.8.5, phosphatidylglycerophosphate synthase) from Escherichia coli has been cloned, using pSC101 as the vector. The resulting hybrid plasmids not only correct the lack of in vitro synthase activity in pgsA strains but also cause an amplification (6- to 40-fold over wild-type levels) in enzymatic activity in direct proportion to the copy number of the plasmids found in vivo. The cloned gene also corrects the abnormally low level of polyglycerophosphatides found in pgsA strains and actually increases the level of phosphatidylglycerol to above that normally found in E. coli. The degree of alteration in phospholipid composition brought about by these hybrid plasmids is not of the order expected if fluctuations in enzyme levels in vivo were an important regulatory mechanism in phospholipid metabolism. The isolated hybrid plasmids have been mapped by restriction endonuclease analysis. The presence and location of other genetic markers have also been established. The above data, along with analysis of deletion derivatives of these plasmids and subcloning of appropriate restriction fragments, have established the position of the pgsA locus on the hybrid plasmids. From this data, the position of the pgsA locus has been determined to le between flaI and uvrC on the E. coli genetic map. PMID- 6267014 TI - Origin of Haemophilus influenzae R factors. AB - The Haemophilus influenzae R plasmids specifying resistance against one, two, or three antibiotics which have emerged in different parts of the world were shown to have closely related but not identical plasmid cores. The gene for ampicillin resistance in the H. influenzae plasmid pKRE5367 is part of a transposon similar to Tn3, which was transposed from pKRE5367 onto RSF1010 in Escherichia coli. An indigenous H. influenzae plasmid (pW266) was isolated. Its properties correspond to those of the H. influenzae R plasmids, except for the presence of a drug resistance transposon. The in vitro-generated H. influenzae R plasmids carrying an ampicillin resistance transposon, a tetracycline resistance transposon, and a transposon for combined tetracycline-chloramphenicol resistance resembled the natural isolates. The findings support the hypothesis that the R plasmids of H. influenzae are of multiclonal evolutionary origin. PMID- 6267015 TI - A mutant defective in partitioning of composite plasmid Rms201. AB - Escherichia coli harboring mutant plasmids defective in maintenance stability (from the conjugative plasmid Rms201) showed a wide distribution of ampicillin resistance levels, as well as increased frequency of plasmid loss from the cell. The amounts of covalently closed circular deoxyribonucleic acid of mutant plasmid Rms268 and parental plasmid Rms201 per chromosome were 5.3 and 6.1%, respectively. The beta-lactamase activities of strains W3630(Rms268) and W3630(Rms201) were 0.56 and 0.44 U/mg of protein, respectively. Frequency of plasmid loss from W3630(Rms268) was about 0.8 to 1.2% per cell generation, 100 times more than that of the wild-type strain. Ampicillin resistance levels of the colonies harboring the mutant plasmid showed a wide distribution, from low (100 micrograms/ml) to high (1,600 micrograms/ml). A miniplasmid (pMS268) with a mass of 7 X 10(6) daltons and encoding ampicillin resistance was isolated from Rms268. Frequency of pMS268 loss from W3630(pMS268) was about 0.8 to 1.9% per cell generation. W3630(pMS268) also showed a wide range of distribution in the levels of ampicillin resistance. These results indicated that the copies of Rms268 in E. coli did not segregate evenly between daughter cells at cell division and that the gene involved was located on the miniplasmid. PMID- 6267016 TI - Structural studies of lambda transducing bacteriophage carrying bacterial deoxyribonucleic acid from the metBJLF region of the Escherichia coli chromosome. AB - The structures of several lambda dmet and related lambda darg transducing phage were studied by restriction fragment mapping and electron microscopic measurements of homoduplexes and heteroduplexes. A new transducing phage (lambda dmet141), in which metF is the only functional gene of the cluster, was isolated. In contrast, lambda dmet117, which expresses the entire metBJLF cluster, has only 3 kilobases more bacterial deoxyribonucleic acid (DNA) than lambda dmet141. An EcoRI restriction fragment of lambda dmet117, which carries the leftmost 6 kilobases of the bacterial DNA insert, was isolated and shown to contain a functional copy of metB. Small structural differences at the attachment sites of some of the phage were shown to result from different sites of lambda integration in the two parent insertion lysogens. PMID- 6267017 TI - Escherichia coli and Salmonella typhimurium supX genes specify deoxyribonucleic acid topoisomerase I. AB - Mutations of the Escherichia coli or Salmonella typhimurium supX genes eliminated deoxyribonucleic acid topoisomerase I. Suppression of a supX amber mutation partially restored the topoisomerase. Multicopy plasmids carrying supX+ caused overproduction of topoisomerase. Thus, these supX genes were identified as topA genes which specify deoxyribonucleic acid topoisomerase I. PMID- 6267018 TI - Use of transposons in cloning poorly selectable genes of Escherichia coli: cloning of uvrA and adjacent genes. AB - A transposon was introduced close to a poorly selectable gene. This gene could be cloned by using selection for the antibiotic resistance marker of the transposon. PMID- 6267019 TI - Isolation of somatic cell mutants defective in the biosynthesis of phosphatidylethanolamine. AB - An in situ autoradiographic assay for CDP-ethanolamine:1,2-sn-diacylglycerol ethanolamine phosphotransferase (EC 2.7.8.1) activity in Chinese hamster ovary cells was developed and used to screen approximately 10,000 individual mutagen treated colonies attached to filter paper (Esko, J. D., and Raetz, C. R. H. (1978) Proc. Natl. Acad. Sci. U. S. A. 75, 1190-1193). A variant (strain 40.11) was isolated in which the ethanolamine phosphotransferase specific activity in vitro was 6-10-fold less than in the parent, but the level of CDP-choline:1,2-sn diacylglycerol choline phosphotransferase (EC 2.7.8.2) activity was normal. In extracts, the mutant was also defective in the synthesis of ethanolamine plasmalogen. In vivo, the short term kinetics of labeling with [32P]phosphate or [14C]ethanolamine was correspondingly altered. However, the long tem growth rate and steady state phospholipid compositions of the mutant and parent were quite similar. These results show that the ethanolamine and choline phosphotransferases of Chinese hamster ovary cells are distinct as judged by genetic criteria, while the biosynthesis of phosphatidylethanolamine and its plasmalogen share common enzymatic component(s). PMID- 6267020 TI - Two forms of purified m7G-cap binding protein with different effects on capped mRNA translation in extracts of uninfected and poliovirus-infected HeLa cells. AB - Eukaryotic mRNA cap binding proteins were purified from ribosomal salt wash in the presence of protease inhibitors by sucrose gradient sedimentation and m7GDP Sepharose affinity chromatography. Rabbit reticulocyte and erythrocyte proteins with sedimentation constants of less than 6 S yielded a approximately 24,000 dalton cap binding protein. It stimulated capped mRNA translation in extracts of uninfected HeLa cells but did not restore capped mRNA function in extracts prepared from poliovirus-infected cells. Restoring and stimulatory activities both were associated with a larger, approximately 8-10 S complex that included the approximately 24,000-dalton polypeptide and several higher molecular mass components. The same two translational activities were also obtained in a slightly smaller approximately 5-7 S complex from uninfected HeLa cells but were absent from poliovirus-infected cell preparations. PMID- 6267021 TI - On the evolutionary relationship of the 4-alpha-helical heme proteins. The comparison of cytochrome b562 and cytochrome c'. AB - The atomic models of the cytochrome b562 and cytochrome c' monomers have been compared. When the respective heme groups are superimposed, the four alpha helices of each nearly coincide. Four aromatic side chains, including the heme ligands, and a methionine occur in spatially equivalent positions in contact with the heme groups. This structural evidence suggests that the two cytochrome families may have diverged from a common molecular ancestor. PMID- 6267022 TI - Target molecular weight of the gastric (H+ + K+)-ATPase functional and structural molecular size. AB - The state of assembly of the (H+ + K+)-ATPase in purified hog gastric mucosa membranes was studied by target size analysis applied to radiation-induced enzyme inactivation and polypeptide degradation data. Radiation inactivated the Mg2+ ATPase, K+-stimulated ATPase, and p-nitrophenyl phosphatase activities of the membrane preparation with a dose dependence characteristic of a target size of 270,000-daltons. Radiation also bleached the major 100,000-dalton sodium dodecyl sulfate-gel electrophoresis band of this preparation, indicating a radiation induced degradation. This apparent polypeptide degradation exhibited a dose dependency corresponding to a target size of 250,000 daltons in situ. It is suggested that the gastric ATPase is a trimeric assembly of the 100,000-dalton polypeptides. PMID- 6267023 TI - The regulation of lipomodulin, a phospholipase inhibitory protein, in rabbit neutrophils by phosphorylation. AB - Lipomodulin, purified to near homogeneity from rabbit peritoneal neutrophils, was phosphorylated by cyclic AMP-dependent protein kinase from bovine heart with concomitant loss of its ability to inhibit phospholipase A2 from porcine pancreas. Phosphorylation of lipomodulin was confirmed by the incorporation of 32P from [gamma-32P]ATP. To demonstrate that lipomodulin undergoes phosphorylation in vivo, rabbit peritoneal neutrophils were incubated with 32P and lipomoculin was isolated by immunoprecipitation with serum from a patient with systemic lupus erythematosus which has anti-lipomodulin antibody. Analysis of 32P-labeled immunoprecipitates by sodium dodecyl sulfate electrophoresis revealed a single peak of radioactivity that comigrated with [35S]methionine labeled lipomodulin. The administration of a chemoattractant, N-formyl-methionyl leucyl-phenylalanine to intact rabbit neutrophils, resulted in a marked increase in arachidonate release from the cells and an increase in 32P incorporation into lipomodulin. A close correlation was found between the extent of phosphorylation of lipomodulin and the rate of arachidonate release. Phosphorylation of lipomodulin in neutrophils gradually returned to the control level with corresponding cessation of arachidonate release. In contrast to the in vitro system, phosphorylation of lipomodulin and release of arachidonic acid from peptide-stimulated neutrophils required Ca2+ entry into the cells. These results suggest that the phosphorylation-dephosphorylation of lipomodulin, phospholipase inhibitory protein, is an important mechanism for chemotactic receptor-mediated regulation of arachidonic acid release in rabbit neutrophils. PMID- 6267024 TI - A free radical mechanism of prostaglandin synthase-dependent aminopyrine demethylation. AB - The mechanism of prostaglandin synthase-dependent N-dealkylation has been investigated using an enzyme preparation derived from ram seminal vesicles. Incubation of an N-alkyl substrate, aminopyrine, with enzyme and arachidonic acid, 15-hydroperoxyarachidonic acid, or tert-butyl hydroperoxide resulted in the formation of the transient aminopyrine free radical species. Formation of this radical species, which was detected by electron paramagnetic resonance spectroscopy and/or absorbance at 580 nm, was maximal approximately 30 s following initiation of the reaction and declined thereafter. Free radical formation corresponded closely with formaldehyde formation in this system, in terms of dependence upon substrate and cofactor concentration, as well as in terms of time course. Both aminopyrine free radical and formaldehyde formation were inhibited by indomethacin and flufenamic acid, inhibitors of prostaglandin synthase. The results suggest that the aminopyrine free radical is an intermediate in the prostaglandin synthase-dependent aminopyrine N-demethylase pathway. The aminopyrine free radical electron paramagnetic resonance spectrum revealed that this species is a one-electron oxidized cation radical of the parent compound. A reaction mechanism has been proposed in which aminopyrine undergoes two sequential one-electron oxidations to an iminium cation, which is then hydrolyzed to the demethylated amine and formaldehyde. Accordingly, the oxygen atom of the aldehyde product is derived from neither molecular nor hydroperoxide oxygen, but from water. PMID- 6267025 TI - Transitory effects of glucose starvation on the synthesis of dolichol-linked oligosaccharides in mammalian cells. AB - The distribution of lipid-linked oligosaccharide intermediates in cultured mammalian cells has been studied under conditions of glucose deprivation. It was found that at low to moderate cell densities within 20 min of glucose starvation, the major species of lipid-linked oligosaccharide shifted from mainly a single species containing three glucose, nine mannose, and two N-acetylglucosamine residues to a pattern dominated by two species containing either five mannose and two N-acetylglucosamine residues or two mannose and two N-acetylglucosamine residues. At high cell densities, this effect was not evident. Continued glucose starvation at low density resulted in a second shift in distribution in which the proportions of these two species decreased and that of the original major species (Glc3Man9GlcNAc2) increased. Addition of glucose or mannose, but not pyruvate, glutamine, galactose, inositol, or glycine, prevented the shift to the Man5GlcNAc2 and Man2GlcNAc2 species. The intermediates that accumulate during glucose starvation were identified by their elution position on gel filtration columns, sensitivity to digestion with alpha-mannosidase, resistance to digestion with endo-beta-N-acetylglucosaminidase H, and by the products of Smith degradation. These data suggest that a regulatory point in the lipid-linked oligosaccharide synthetic pathway exists at the reaction in which Man5GlcNAc2-P-P dolichol is converted to Man6GlcNAc2-P-P-dolichol. PMID- 6267026 TI - Affinity labeling of a human platelet membrane protein with 5'-p fluorosulfonylbenzoyl adenosine. Concomitant inhibition of ADP-induced platelet aggregation and fibrinogen receptor exposure. AB - Incubation of washed human blood platelets with 5'-p-fluorosulfonylbenzoyl [3H]adenosine (FSBA) covalently labels a single polypeptide of Mr = 100,000. Protection by ADP has suggested that an ADP receptor on the platelet surface membrane was modified. The modified cells, unlike native platelets, failed to aggregate in response to ADP (100 microM) and fibrinogen (1 mg/ml). The extent of binding of 125I-fibrinogen and aggregation was inhibited to a degree related to the incorporation of 5'-p-sulfonylbenzoyl adenosine (SBA) into platelets, indicating FSBA could inhibit the exposure of fibrinogen receptors by ADP necessary for aggregation. Incubation of SBA platelets with alpha-chymotrypsin cleaved the covalently labeled polypeptide and concomitantly reversed the inhibition of aggregation and fibrinogen binding. Platelets proteolytically digested by chymotrypsin prior to exposure to FSBA did not require ADP for aggregation and fibrinogen binding. Moreover, subsequent exposure to FSBA did not inhibit aggregation or fibrinogen binding. The affinity reagent FSBA can displace fibrinogen bound to platelets in the presence of ADP, as well as promote the rapid disaggregation of the platelets. The apparent initial pseudo-first order rate constant of dissociation of fibrinogen was linearly proportional to FSBA concentrations. These studies suggest that a single polypeptide can be altered either by ADP-induced conformational changes or proteolysis by chymotrypsin to reveal latent fibrinogen receptors and promote aggregation of platelets after fibrinogen binding. PMID- 6267027 TI - Amino acid-specific ADP-ribosylation. Identification of an arginine-dependent ADP ribosyltransferase in rat liver. AB - A partially purified protein preparation from rat liver catalyzed the ADP ribosylation of low molecular weight guanidino compounds and proteins. Agmatine and arginine, previously shown to be effective acceptors for the guanidine dependent erythrocyte ADP-ribosyltransferase, were used as acceptors by the rat liver enzyme; lysine, histidine, and serine were inactive. The product of the reaction between [adenine-U-14C]NAD and agmatine catalyzed by the rat liver enzyme co-chromatographed with [adenine-U-14C]ADP-ribose-agmatine which was synthesized by the erythrocyte transferase; in parallel assays, formation of this product was associated with stoichiometric release of [carbonyl-14C]nicotinamide from [carbonyl-14C]NAD. In the presence of histones or other proteins and [adenine-U-14C]NAD or [32P]NAD, the rat liver enzyme catalyzed the formation of a radioactive product which was precipitable by trichloroacetic acid. Digestion of the [adenine-U-14C]-labeled precipitate with snake venom phosphodiesterase released a labeled compound identified as 5'-AMP. These data are consistent with the conclusion that a mono-(ADP-ribosyltransferase) is present in rat liver which utilizes guanidino compounds such as arginine as ADP-ribose acceptors. The ADP ribose-glutamate bond has been shown to exist in rat liver. Since the catalytic sites of each transferase can accommodate and thus ADP-ribosylate only one specific amino acid, a family of site-specific transferases must be present. The availability of multiple site-specific transferases permits the cell to exert further control over ADP-ribosylation. PMID- 6267028 TI - Single crystal EPR of myoglobin nitroxide. Freezing-induced reversible changes in the molecular orientation of the ligand. AB - Single crystals of myoglobin nitroxide (MbNO) are examined by the electron paramagnetic resonance spectroscopy at ambient and cryogenic temperatures for both the 14NO and 15NO derivatives. The principal values and the eigenvectors of the g tensor and the hyperfine coupling tensor are determined: g xx = 2.050, g yy = 2.022, and g zz = 1.993; A xi xi = 15.6, A zeta zeta = 21.4, and A eta eta = 26.7 G for the nitrogen in 15NO at ambient temperature. The Fe--N--O bond angle is calculated to be 153 degrees. This result is in good agreement with the x-ray structural result on the six-liganded model compound with the bent Fe--N--O configuration. The principal values and the eigenvectors of the g tensor and the hyperfine coupling tensor are also determined at 77 K for Mb15NO; gxx = 2.076, gyy = 1.979, and gzz = 2.002; A xi xi = 21, A zeta zeta = 24, and A eta eta = 27 G. The Fe--N--O bond angle is calculated to be 109 degrees. The hyperfine splittings attributed to N epsilon atom of proximal histidine are observed in the direction of the gzz at both temperatures. The drastic shift of the EPR spectrum of MbNO single crystal is observed below the freezing point of this crystal. It clearly demonstrates that the conformation of the bonding NO is drastically altered upon freezing. The temperature dependence of the EPR spectra of MbNO below the freezing point cannot be explained only by appropriate combinations of the higher temperature type and the lower temperature type and suggests the contribution from an unpaired electron with the iron dz2 and dyz (or dxz) orbitals. The present EPR results demonstrated that the changes in the molecular orientations are induced by freezing of the biological molecules without disorder of the crystal lattice. PMID- 6267029 TI - Studies on the function of the two intrachain cAMP binding sites of protein kinase. PMID- 6267030 TI - Identification and sequence analysis of the 5' domain of the X and Y pseudo ovalbumin genes. AB - The expression of the X and Y pseudo-ovalbumin genes is stimulated by estrogen to a much lesser extent than the expression of the authentic ovalbumin gene in the chicken oviduct. Since it is possible that the primary structures of the 5' flanking regions of these genes are responsible for their differential hormonal responses, we have identified the 5' transcription domains of the X and Y pseudo ovalbumin genes and determined their nucleotide sequences. Similar to many other eukaryotic genes, the X, Y, and ovalbumin genes each contain an (A + T)-rich heptamer located about 30 nucleotides upstream from the cap site. This sequence is TATATAT for the X and ovalbumin genes, but GATATAT for the Y gene. The 5' flanking sequences of all three genes are about 70% homologous when allowances are made for deletions and insertions. There is no obvious feature of the 5' flanking sequences of the pseudo-ovalbumin genes which can be related to differential hormonal responsiveness. Nevertheless, these 5' flanking regions appear to have been conserved relative to the intervening sequences of the pseudogenes, and thus may be important to gene function. PMID- 6267031 TI - Inhibition of epidermal growth factor binding to mouse embryonal carcinoma cells by phorbol esters mediated by specific phorbol ester receptors. PMID- 6267032 TI - Characterization of the potentiometric behavior of soluble cytochrome oxidase by magnetic circular dichroism. Evidence in support of heme-heme interaction. AB - Magnetic circular dichroism spectroscopy has been used to characterize the oxidation-reduction behavior of cytochromes a and a3 during potentiometric experiments. The experiments were complicated by the presence of slow, time dependent changes during reduction, and it appears that reliable results can only be obtained during reoxidation or with enzyme that has been subjected to a cycle of reduction and oxidation. Under all experimental conditions the reduction levels of cytochrome a and a3 are comparable. This result cannot be reconciled with a model in which the two heme centers have defined and well resolved potentials. The most straightforward explanation of the data requires an oxidation-reduction coupling of the potentials of the two hemes, i.e. an allosteric or heme-heme interaction, which is about 2 K cal/mol in magnitude. There is a good correlation between magnetic circular dichroism and EPR measurements obtained on parallel samples. The kinetics of the slow, time dependent processes have been characterized by measurement of a variety of spectral properties and enzyme activity. All parameters measured change at comparable rates, implying a common rate-controlling event. A new copper EPR signal has been observed at high pH. This signal appears to rise from the "EPR undetectable" copper center. PMID- 6267033 TI - Primary structure of the major human pituitary pro-opiomelanocortin NH2-terminal glycopeptide. Evidence for an aldosterone-stimulating activity. AB - The isolation and complete purification of a human glycopeptide representing the major immunoreactive form of the pituitary NH2-terminal segment of pro opiomelanocortin is presented. The complete sequence of this peptide was determined following CNBr fragmentation and it is shown to be 76 amino acids long. It bears an O-glycosylation site at Thr 45 and an N-glycosidic linkage at Asn 65. Compared to the reported genomic DNA sequence (Chang, A. C. Y., Cochet, M., and Cohen, S. N. (1980) Proc. Natl. Acad. Sci. U. S. A. 77, 4890-4894), one variation exists, namely Arg 22 replacing Gly 22. Two disulfide bridges linking Cys 2 to 8 and Cys 20 to 24 have been determined. Based on the sequence and disulfide bridge localization, a large degree of homology exists between the NH2 terminal sequence of the human peptide and all calcitonins, especially porcine calcitonin. The human NH2-terminal peptide is shown to stimulate the release of aldosterone from isolated cells of a human adrenal tumor, in at least equipotency to adrenocorticotropic hormone and the porcine NH2-terminal analogue, which is 100 times more potent than angiotensin II. Finally, this reported sequence completes that of the human DNA which was lacking the first 19 amino acids due to the presence of a 2-kilobase intron. PMID- 6267034 TI - Permeability properties of chemically modified porin trimers from Escherichia coli B. AB - The pore-forming protein of the outer membrane of Escherichia coli, porin, was chemically modified with acetic anhydride, succinic anhydride, and glycinamide. Extensive modification of amino groups of the functional porin trimers caused reduced diffusion rates of the negatively charged solutes such as p-nitrophenyl phosphate and AMP, but did not reduce significantly the diffusion of positively charged molecules carbobenzoxy-glycyl-prolyl-arginine-p-nitranilide and tosyl glycyl-prolyl-arginine-p-nitranilide. Modification of carboxyl groups of trimers caused decreased diffusion rates of the positively charged solutes more significantly than the diffusion rates of negatively charged solutes. The results suggest that the ionic interactions play an important role for the diffusion of charged solutes through the porin pore. The diffusion of p-nitrophenyl alpha-D glucoside, an uncharged solute, ws not influenced significantly by modification of either amino or carboxyl groups. This observation suggests that modifications only occurred in areas outside of the narrowest portion of the pore or, alternatively, that amino and carboxyl groups are exclusively located at noncylindrical area of the pore. The structural integrity of the acetylated and the succinylated trimers seemed well preserved. On the other hand, modification of carboxyl groups decreased the thermal stability of trimers and extensive modifications caused the dissociation of trimers into monomers at 37 degrees C. PMID- 6267035 TI - Phosphorylation and activation of the cardiac isoenzyme of phosphorylase kinase by the cAMP-dependent protein kinase. AB - The cAMP-dependent protein kinase catalyzes the phosphorylation of the alpha- and beta-subunits of the cardiac isozyme of phosphorylase kinase. beta-Subunit phosphorylation achieves a maximum level of between 1 to 2 mol of phosphate/mol of phosphorylase kinase, a value less than the stoichiometric content of beta subunits in the enzyme. This, less than stoichiometric incorporation, is not a result of the presence of endogenous phosphate in equivalent sites in the remaining beta-subunit moieties. Pretreatment of phosphorylase kinase with phosphoprotein phosphatase, under conditions proven to dephosphorylate such sites, does not modify the observed extent of beta-subunit phosphorylation. alpha'-Subunit phosphorylation is initiated at a slower rate than beta but achieves a higher maximum level of incorporation. alpha'-Subunit phosphorylation, but not the extent of beta-subunit phosphorylation, is stimulated by MnCl2 and partially inhibited by NaF; neither is effected by ethylene glycol bis(beta aminoethyl ether)-N,N,N',N'-tetraacetic acid. The activation of cardiac phosphorylase kinase that occurs concomitantly with phosphorylation appears to be dependent upon phosphate incorporation into both the alpha- and beta-subunits. At low levels of activation a close correlation is observed between activation and either alpha-subunit phosphorylation, beta-subunit phosphorylation, or total phosphorylation. However, the cAMP-dependent catalyzed phosphorylation of alpha, at a time after which beta-subunit phosphorylation is already maximal, also results in activation of cardiac phosphorylase kinase. PMID- 6267036 TI - The effect of the method of isolation on the surface properties of isolated rat hepatocytes. PMID- 6267038 TI - Transcription and site-specific hypomethylation of the delta-crystallin genes in the embryonic chicken lens. AB - Chicken delta-crystallin has at least two similar genes containing multiple intervening sequences. Hybridization experiments utilizing DNA probes derived from intervening sequences contained within cloned delta-crystallin gene fragments indicated that both of these two delta-crystallin genes are transcribed in the embryonic lens. No evidence for transcription of these genes was found in nuclei prepared from decapitated chicken embryos. Comparison of restriction enzyme digests of genomic DNA prepared from lens and non-lens tissues showed that the delta-crystallin gene sequences are not grossly rearranged in the lens during development. Msp I and Hpa II digests revealed that there are at lest three -CCGG sites in the delta-crystallin genes that are hypomethylated in the embryonic lens DNA but are hypermethylated in sperm, red blood cell, or headless embryo DNAs. The delta-crystallin genes were not transcribed and these three sites were methylated in embryonic lens epithelial cells that were transformed with a temperature-sensitive Rous sarcoma virus. These results associate delta crystallin gene transcription and site-specific hypomethylation of the delta crystallin DNA. PMID- 6267037 TI - Purification and characterization of DNase VII, a 3' leads to 5'-directed exonuclease from human placenta. AB - An exonuclease, DNase VII, has been purified 6000-fold from human placenta. The enzyme has an apparent molecular weight of 43,000, requires Mg2+ for activity, and has a pH optimum of 7.8. The enzyme hydrolyzes single-stranded and nicked duplex DNA at the same rate proceeding in a 3' leads to 5' direction liberating 5'-mononucleotides. It does not measurably hydrolyze polyribonucleotides. PMID- 6267039 TI - Nucleotide sequence of the gene for ribosomal protein S20 and its flanking regions. AB - The sequence of almost 700 nucleotides encompassing the gene for ribosomal protein S20 of Escherichia coli has been determined using the chemical technique of Maxam and Gilbert (Maxam, A. M., and Gilbert, W. (1977) Proc. Natl. Acad. Sci. U. S. A. 74, 560-564). Comparison of this sequence with that of known bacterial promoters reveals two promoter-like sequences whose putative initiation sites for transcription lie 132 ("site 1") and 42 ("site 2") base pairs to the 5' side of the coding sequence. Partial digestion experiments demonstrate that RNA polymerase is capable of binding to and protecting both of these sites from DNase 1 digestion, consistent with their functioning as promoters. Interestingly, site 1 is more compact that any previously described bacterial promoter. A second feature of the sequence is the presence of UUG as the translational initiation codon. Finally, the nucleotide sequence supports the hypothesis (Jue, R. A., Woodbury, N. W., and Doolittle, R. F. (1980) J. Mol. Evol. 15, 129-148) that S20 is composed of three tandemly repeated domains. PMID- 6267040 TI - Interaction of calmodulin with myosin light chain kinase and cAMP-dependent protein kinase in bovine brain. AB - Myosin light chain kinase and a fraction of type II cAMP-dependent protein kinase have been partially purified from bovine brain by affinity chromatography on calmodulin-Sepharose. The myosin kinase was purified approximately 3700-fold and has an estimated molecular weight of 130,000 +/- 10,000 by sodium dodecyl sulfate gel electrophoresis. A fraction of soluble cAMP-dependent protein kinase also bound to calmodulin-Sepharose and was purified 2300-fold. A fraction of this cAMP dependent protein kinase after purification by glycerol gradient centrifugation was shown to contain the two subunits of calcineurin, a major calmodulin-binding protein in brain, and the two subunits of type II cAMP-dependent protein kinase in a ratio of 1:1:2:2. Its sedimentation coefficient was 8.1 S and 9.0 S when centrifuged in the absence or presence of calmodulin, suggesting the formation of a complex between calmodulin and protein kinase. Our results suggest the possibility that calcineurin may be involved in the interaction between the protein kinase and calmodulin. Furthermore, our studies imply that the regulatory subunit of the cAMP-dependent protein kinase, but not the catalytic subunit, is the site of interaction with calmodulin since the catalytic subunit of protein kinase was partially resolved from the complex by cAMP. PMID- 6267041 TI - The effects of subfractions of high density lipoprotein on cholesterol efflux from cultured fibroblasts. Regulation of low density lipoprotein receptor activity. PMID- 6267042 TI - Primary structure of the low molecular weight nucleic acid-binding proteins of murine leukemia viruses. AB - Murine leukemia viruses contain a low molecular weight basic protein, designated p10, which binds to single-stranded nucleic acids. The complete amino acid sequence of p10 from the Rauscher strain of virus has been determined. The partial amino acid sequences of p10s from Moloney, Friend, AKR, Gross, radiation leukemia, and BALB/2 viral strains have also been determined using microsequencing techniques. Rauscher p10 is composed of 56 amino acid residues; the other p10s are similar in size but differ from Rauscher by a few conservative amino acid substitutions. The structure of Rauscher p10 was compared to the structure of a functionally homologous protein from Rous avian sarcoma virus. The comparison revealed regions of amino acid sequence homologies which indicate a phylogenetic relationship between the murine and avian viral strains. The analyses revealed a periodic placement of three Cys residues and a Gly-His sequence. A structure involving these residues is found once in the murine protein and twice in the avian protein. A similar structure is seen in the single stranded nucleic acid binding protein of bacteriophage T4. However, in the latter case, the order of amino acid residues is inverted. PMID- 6267043 TI - The exon/intron structure of the 3'-region of the pro alpha 2(I) collagen gene. PMID- 6267044 TI - Characterization of serum-induced alterations in the cyclic AMP pathway in S49 lymphoma cells. PMID- 6267046 TI - Hormonally sensitive cyclic AMP phosphodiesterase in liver cells. An ecto-enzyme. AB - Ecto-cyclic AMP phosphodiesterase activity was determined from freshly isolated and cultured liver cells. The cells were capable of hydrolyzing cyclic AMP in the medium. The ecto-phosphodiesterase represents a low Km phosphodiesterase which was activated by physiological concentrations of insulin. The product, 5'-AMP, was recovered in the medium and not with the cells. The enzyme was inhibited with aminophylline and trypsin. The ecto-phosphodiesterase activity was proportional to cell number, and total phosphodiesterase activity increased 5- to 10-fold when the cells were ruptured. About one-third of the ecto-phosphodiesterase activity from freshly isolated liver was due to phosphodiesterase in the medium. No phosphodiesterase was in the medium of cultured liver cells. PMID- 6267045 TI - Hyaluronate-protein complex of rous sarcoma virus-transformed chick embryo fibroblasts. AB - Involvement of covalently linked protein or peptide in the structure or synthesis of hyaluronate has not previously been convincingly demonstrated. We have developed conditions for double-labeling with [3H]leucine and [14C]acetate, then isolating and characterizing the cell-associated and secreted hyaluronate-protein complexes of Rous sarcoma virus-transformed chick embryo fibroblasts. The preparations were purified by Bio-Gel A-15m gel filtration and CsCl density gradient ultracentrifugation under dissociative conditions, followed by acid agarose gel electrophoresis in the presence of 0.1% Nonidet P-40. The purified hyaluronate preparations did not change their 3H:14C ratios after further sodium dodecyl sulfate or alkali treatment. The cell-derived hyaluronate-protein was resistant to pronase but susceptible to proteinase K in the presence of sodium dodecyl sulfate. After chondroitinase ABC digestion, the cell-derived 3H-labeled protein was separated from the 14C-labeled hyaluronate disaccharides, then shown to give a broad band corresponding to Mr approximately 12,000 on sodium dodecyl sulfate-urea polyacrylamide gel electrophoresis and to be susceptible to both pronase and proteinase K. The corresponding 3H-labeled peptide was prepared in the same manner from the medium hyaluronate and the [3H]leucine shown to be present in material smaller in amount and size than that from the cell. We propose from these and other published data that the cell-associated hyaluronate protein may be bound to the cell surface and that the hyaluronate in the medium may be derived from it as a result of proteolytic scission. PMID- 6267047 TI - Diphtheria toxin. Site and configuration of ADP-ribosylation of diphthamide in elongation factor 2. AB - Diphtheria toxin inactivates protein synthesis elongation factor 2 by catalyzing the ADP-ribosylation of a novel derivative of histidine, diphthamide, in the protein (Van Ness, B. G., Howard, J. B., and Bodley, J. W. (1980) J. Biol. Chem. 255, 10710-10716). In this report, we describe experiments involving nuclear Overhauser enhancement NMR spectroscopy which were undertaken to elucidate the site of ADP-ribosylation of diphthamide and the configuration of the glycosidic bond formed by the toxin. The essential result of these experiments is that, in ribosyl-diphthamide obtained by enzymatic digestion of ADP-ribosyl-elongation factor-2, the H-5 imidazole proton is near the R-4 proton of ribose. This result and others are consistent with the interpretation that diphtheria toxin covalently attaches ADP-ribose to the imidazole N-1 of diphthamide via an alpha glycosidic linkage. PMID- 6267048 TI - Formation of a cytochrome c-like species from horse apoprotein and hemin catalyzed by yeast mitochondrial cytochrome c synthetase. AB - Cytochrome c synthetase in yeast mitochondria catalyzes the formation of a yeast cytochrome c-like species from the apoprotein and hemin (Basile, G., DiBello, C., and Taniuchi, H. (1980) J. Biol. Chem. 255, 7181-7191). To test the specificity of this enzyme, 125I-labeled horse apocytochrome c was incubated with the yeast mitochondrial fraction in the presence of hemin, NADPH, and an ethanol extract of the postmitochondrial fraction. A radioactive 125I-labeled cytochrome c-like species was formed in yields of up to 26%. This 125I-labeled species is indistinguishable from horse cytochrome c by ion exchange chromatography (under the conditions which allow separation of horse and yeast cytochrome c), resistance in its reduced form to digestion by trypsin, resistance against autoxidation, reduction by cytochrome b2, and generation of the apoprotein after treatment with silver sulfate and dithiothreitol. With unlabeled horse apoprotein and [59Fe]hemin, the yield of a [59Fe-labeled horse cytochrome c-like species was up to 7% with respect to the apoprotein incubated. The yield of the 59Fe-labeled species was not altered by the addition of unlabeled FeCl3. Conversely, synthesis of the 59Fe-labeled species was not detectable after incubation of yeast mitochondria with unlabeled horse apoprotein, unlabeled hemin, and 59FeCl3. The formation of both 125I- and 59Fe-labeled cytochrome c-like species was sensitive to heat. Thus, we conclude that cytochrome c synthetase catalyzes direct bonding of heme (or hemin) to the apoprotein. Since the amino acid sequences of horse and yeast cytochromes c differ considerably, cytochrome c synthetase may recognize only a limited region(s) of the apoprotein. PMID- 6267050 TI - Modulation of nuclear protein kinase activity and phosphorylation of histone H1 subspecies during the prereplicative phase of rat liver regeneration. AB - We have measured nuclear protein kinase activity during the prereplicative phase of rat liver regeneration. Total nuclear protein kinase activity increased significantly 15-18 h after partial hepatectomy, with the peak of activity occurring at 16 h. DEAE-Sephacel chromatography resolved nuclear protein kinase activity into two cAMP-independent (Ib and II) and two cAMP-dependent (Ia and III) protein kinases. Sixteen h after partial hepatectomy, there was a marked increase in the activities of the nuclear cAMP-dependent protein kinases and a decrease in the activity of nuclear cAMP-independent protein kinase II. Characterization of the two nuclear cAMP-dependent protein kinases revealed them to be identical with the cytosolic type I and II isozymes. Immunotitration of nuclear catalytic subunit and densitometric analysis of autoradiographs from 8 azido-[32P]cAMP-labeled nuclear RI revealed increases in both subunits 16 h afer partial hepatectomy. Concomitantly with the observed increase in nuclear protein kinase activity, we have observed an increase in the phosphorylation of histone H1 subspecies. Administration of the beta-adrenergic antagonist DL-propranolol, which has been shown to cause delays of equal duration in both the second phase of increased intracellular cAMP levels and the initiation of DNA synthesis (MacManus, J. P., Braceland, B. M., Youdale, T., and Whitfield, J. F. (1973) J. Cell. Physiol. 82, 157-164), results in an equivalent delay of increased nuclear protein kinase activity. Colchicine, which has previously been shown to prevent the onset of DNA synthesis (Walker, P. R., and Whitfield, J. F. (1978) Proc. Natl. Acad. Sci. U. S. A. 75, 1394-1398), also prevents the increased protein kinase activity normally observed 16 h after partial hepatectomy. We conclude that the onset of DNA synthesis in the regenerating rat liver is preceded by a cAMP-mediated translocation of type I and type II cAMP-dependent protein kinase to the nucleus and phosphorylative modification of histone H1 subspecies. The inhibitory effects of propranolol and colchicine suggest a common cAMP-mediated, colchicine-sensitive link between protein kinase translocation and the initiation of DNA synthesis. PMID- 6267049 TI - Evidence that a beta-adrenergic receptor-associated guanine nucleotide regulatory protein conveys guanosine 5'-O-(3-thiotriphosphate)- dependent adenylate cyclase activity. AB - The guanine nucleotide regulatory protein component (N) of the frog erythrocyte membrane adenylate cyclase system appears to form a stable complex with the beta adrenergic receptor (R) in the presence of agonist (H). This agonist-promoted ternary complex HRN can be solubilized with Lubrol. The guanine nucleotide regulatory protein associated with the solubilized complex can be adsorbed either to GTP-Sepharose directly or to wheat germ lectin-Sepharose via its interaction with the receptor which is a glycoprotein. Guanosine 5'-O-(3 thiotriphosphate)(GTP gamma S) can be used to elute the guanine nucleotide regulatory protein from either Sepharose derivative. The resulting N.GTP gamma S complex conveys nucleotide-dependent adenylate cyclase activity when combined with a Lubrol-solubilized extract of turkey erythrocyte membranes. The ability to observe GTP gamma S-dependent reconstitution of adenylate cyclase activity in the eluate from either resin required the formation of the HRN complex prior to solubilization. The N protein can be identified by its specific [32P]ADP ribosylation catalyzed by cholera toxin in the presence of [32P]NAD+. The existence of a stable HRN intermediate complex is supported by the observation that agonist pretreatment of frog erythrocyte membranes results in a 100% increase in the amount of 32P-labeled N protein eluted from the lectin-Sepharose in the presence of GTP gamma S compared to membranes pretreated with either antagonist or agonist plus GTP. Our results therefore provide evidence that the same guanine nucleotide-binding protein that associates with the beta-adrenergic receptor in the presence of agonist mediates adenylate cyclase activation. PMID- 6267051 TI - Biochemical characterization of pp60src-associated protein kinase from avian sarcoma virus Schmidt-Ruppin strain. PMID- 6267052 TI - Chromatin assembly. Relationship of chromatin structure to DNA sequence during simian virus 40 replication. AB - The accessibility of five specific DNA sequences to six different single site restriction endonucleases was evaluated in replicating and mature simian virus 40 chromosomes isolated by three different methods. Electron microscopic and gel electrophoretic analysis of the DNA digestion products demonstrated that DNA accessibility in chromatin was established within 400 base pairs of replication forks and remained essentially unchanged during production of mature chromosomes and their subsequent re-entry into the replication pool. Saturating amounts of each enzyme reproducibly cut a fraction of the chromosomes, ranging from 13 to 49%. This is consistent with a nearly random phasing of chromatin structure. Examples in which all chromosomes were either cleaved or intact were never observed. Although variation in the accessibility of DNA sites near the origin of replication could be interpreted as preferred phasing in about 25% of the chromosomes, the finding that two isoschizomers, Hpa II and Msp I, did not cut chromosomes to the same extent precludes an unambiguous interpretation of the extents of cleavage of individual restriction enzymes. Since the extent of DNA cleavage observed at each restriction site was essentially indistinguishable in replicating as compared to mature chromosomes, the accessibility of DNA sequences near the origin is not obviously related to replication. Furthermore, the accessibility of DNA sites on one arm of a single replication fork was the same as the homologous sites on the other arm, consistent with a nearly random phasing of chromatin structure on both arms. This suggests that chromatin assembly occurs independently on the 2 sibling molecules of a single replicating chromosome. PMID- 6267053 TI - ATP-citrate lyase. Structure of a tryptic peptide containing the phosphorylation site directed by glucagon and the cAMP-dependent protein kinase. AB - [32P]ATP-citrate lyase phosphorylated by the cAMP-dependent protein kinase was partially digested by trypsin. Two tryptic 32P-labeled phosphopeptides containing more than 90% of the 32P radioactivity present on the phosphorylated enzyme were purified and found to have overlapping amino acid sequences around the same phosphorylated site (Thr-Ala-Ser(32P)-Phe-Ser-Glu-Ser-Arg). Tryptic digestion of 32P-labeled ATP-citrate lyase purified from 32P-labeled hepatocytes exposed to glucagon yielded a major 32P-labeled peptide of identical amino acid composition with that indicated above. Thus, the site on ATP-citrate lyase phosphorylated by the cAMP-dependent protein kinase in vitro resides on the same octapeptide as the site of glucagon-stimulated phosphorylation in intact hepatocytes. PMID- 6267054 TI - Characterization of the asialoglycoprotein receptor in a continuous hepatoma line. AB - The asialoglycoprotein receptor has been identified on a continuous human hepatoma cell line, HepG2. This receptor requires Ca2+ for ligand binding and is specific for asialoglycoprotein. There are approximately 150,000 ligand molecules bound/cell at 4 degrees C. These receptors represent a homogeneous population of high affinity binding sites with Kd = 7 X 10(-9) M. From the rate of 125I-ASOR binding at 4 degrees C, kon was 0.95 X 10(6) M-1 min-1. Uptake of 125I-ASOR at 37 degrees C was approximately 0.02 pmol/min/10(6) cells. PMID- 6267056 TI - ATP-dependent activation of adenylate cyclase. AB - Incubation of rat liver plasma membranes with MgCl2, ATP, and an ATP-regenerating system at 4 degrees C provides a 4-7-fold persistent activation of adenylate cyclase. Enzyme activation is time-dependent and 48 h of incubation is usually required to achieve maximal stimulation of adenylate cyclase activity. The activation described is not affected by GTP, cAMP, or cGMP, and does not occur when ATP is replaced by a nonphosphorylating analogue, adenyl-5' imidodiphosphate. In addition to ATP, the activation requires Mg2+ and an ATP regenerating system. The activation described is not additive with that produced by fluoride and analysis of basal and fluoride activities following extended incubation for 48 h reveals identical activities which decay at the same rate. These results are consistent with our model (11) which invokes phosphorylation dephosphorylation mechanisms in regulating adenylate cyclase activity. PMID- 6267055 TI - Growth hormone stimulates drug-induced porphyrin formation in liver cells maintained in a serum-free medium. AB - Human growth hormone and a few other related polypeptide hormones enhanced porphyrin formation induced by 2-allyl-2-isopropylacetamide in chick embryo liver cells maintained in a serum-free medium. The stimulatory effect of human growth hormone on drug-induced porphyrin formation was significant at 10 ng/ml and increased in a dose-dependent manner. Human growth hormone did not stimulate porphyrin formation in otherwise untreated cultures. These findings thus demonstrate a potentiating effect of growth hormones on hepatic porphyrin formation. PMID- 6267058 TI - Re-examination of the reaction of diethyldithiocarbamate with the copper of superoxide dismutase. AB - The reaction of the copper of (Cu,Zn)-superoxide dismutase with diethyldithiocarbamate was studied at pH = 7.4 and the results obtained led to a reaction scheme basically different from the conclusion of a previous study (Misra, H. P. (1979) J. Biol. Chem. 254, 11623-11628). The analysis of optical and ESR spectra at 9 and 35 GHz, at different ligand/protein ratios and reaction times, showed that a ternary diethyldithiocarbamate. Cu(II).protein complex never formed in spectroscopically detectable amounts. The system is described in any condition as the mixture, in variable proportions, of only two components, that is the diethyldithiocarbamate-free (Cu(II) chelate and the copper-depleted protein. The formation of a catalytically active copper-diethyldithiocarbamate intermediate with distinct optical and ESR spectra was also ruled out by kinetic studies, which demonstrated that enzyme inactivation strictly parallels the binding of diethyldithiocarbamate as monitored by optical absorption and ESR. Separation of the copper complex from the protein was obtained for the first time, and the procedure was suitable for rapid preparation of reconstitutable copper-free superoxide dismutase. PMID- 6267057 TI - Effects of the myeloperoxidase system on fluorescent probes of granulocyte membrane potential. AB - Activation of normal or myeloperoxidase-deficient human granulocytes by phorbol myristate acetate resulted in an initial membrane depolarization as indicated by an increase in fluorescence of the lipophilic cation probe of membrane potential, 3,3'-dipropylthiodicarbocyanine. A subsequent apparent hyperpolarization (decrease in fluorescence) was observed in normal but not myeloperoxidase deficient cells. Addition of purified myeloperoxidase restored a normal pattern of fluorescence changes to the enzyme-deficient granulocytes. The secondary decrease in fluorescence in normal cells was markedly blunted by addition of azide, cyanide, or catalase. In a cell-free system, the fluorescence of 3,3' dipropylthiodicarbocyanine, but not that of 3,3'-dipentyloxadicarbocyanine, was rapidly eliminated by myeloperoxidase in the presence of hydrogen peroxide and a halide; this loss of fluorescence was inhibited by azide, cyanide, or catalase. These findings indicate that secretion of myeloperoxidase and hydrogen peroxide by activated granulocytes results in decreased fluorescence of 3,3' dipropylthiodicarbocyanine, probably by thioether oxidation. While the determination of initial rates of depolarization using this probe is unaffected by the myeloperoxidase system, measurement of extent of depolarization and any subsequent membrane potential changes requires the addition of inhibitors. In the absence of inhibitors, the secondary decrease in fluorescence can be used as an indicator of secretion of myeloperoxidase and hydrogen peroxide. PMID- 6267060 TI - Replication of polyoma DNA in nuclei isolated from azidocytidine-inhibited fibroblasts. PMID- 6267059 TI - The reaction of reduced xanthine oxidase with oxygen. Kinetics of peroxide and superoxide formation. AB - Product formation during the oxidation of xanthine oxidase has been examined directly by using cytochrome c peroxidase as a trapping agent for hydrogen peroxide and the reduction of cytochrome c as a measure of superoxide formation. When fully reduced enzyme is mixed with high concentrations of oxygen, 2 molecules of H2O2/flavin are produced rapidly, while 1 molecule of O2-/flavin is produced rapidly and another produced much more slowly. Time courses for superoxide formation and those for the absorbance changes due to enzyme oxidation were fitted successfully to the mechanism proposed earlier (Olson, J. S., Ballou, D. P., Palmer, G., and Massey, V. (1974) J. Biol. Chem. 249, 4363-4382). In this scheme, each oxidative step is initiated by the very rapid and reversible formation of an oxygen.FADH2 complex (the apparent KD = 2.2 X 10(-4) M at 20 degrees C, pH 8.3). In the cases of 6- and 4-electron-reduced enzyme, 2 electrons are transferred rapidly (ke = 60 s-1) to generate hydrogen peroxide and partially oxidized xanthine oxidase. In the case of the 2-electron-reduced enzyme, only 1 electron is transferred rapidly and superoxide is produced. The remaining electron remains in the iron-sulfur centers and is removed slowly by a second order process (ks = 1 X 10(4) M-1 s-1). When the pH is decreased from 9.9 to 6.2, both the apparent KD for oxygen binding and the rapid rate of electron transfer are decreased about 20-fold. This result is suggestive of uncompetitive inhibition and implies that proton binding to the enzyme-flavin active site affects primarily the rate of electron transfer, not the formation of the initial oxygen complex. PMID- 6267061 TI - The effect of proteolysis on the calmodulin activation of cyclic nucleotide phosphodiesterase. AB - A high Km cytoplasmic cyclic nucleotide phosphodiesterase (EC 3.4.1.17) has been obtained from bovine brain. The unproteolyzed enzyme contains (63 +/- 1) X 10(3) molecular weight polypeptide chains which exhibit little if any basal catalytic activity. Complexation with calmodulin stimulates the catalytic activity nearly 2 orders of magnitude, presumably, by causing a conformational change in the enzyme which either creates or exposes the catalytic sites. Removal of about 120 amino acids from the terminal portion(s) of each polypeptide chain either by an endogenous protease or by exogenous trypsin prevents calmodulin complexation and generates a basal catalytic activity equivalent to that of the unproteolyzed enzyme-calmodulin complex. In contrast to affinity chromatography using immobilized calmodulin, blue dextran-Sepharose chromatography can be used to select for enzyme containing only unproteolyzed polypeptide chains. PMID- 6267062 TI - Effects of viral transformation on synthesis and secretion of collagen and fibronectin-like molecules by embryonic chick chondrocytes in culture. AB - Monolayer cultures of chondrocytes isolated from 11-day-old chick embryo vertebral cartilage were transformed by Rous sarcoma virus, and the effects of transformation on synthesis and secretion of extracellular proteins by these cells were studied. Transformation resulted in decreased synthesis of type II collagen which did not appear to be due to underhydroxylation of collagenous protein but to a decrease in the total amount synthesized. Carboxymethyl cellulose chromatography and polyacrylamide disc gel electrophoresis failed to demonstrate any alpha 2 chains as a result of the transformation, suggesting that conversion of type II to type I collagen did not occur. In contrast to the decrease in collagen synthesis, synthesis of a molecule with biochemical characteristics similar to fibronectin increased markedly in virally transformed cultures. Although there were no significant differences in the amount of fibronectin-like molecules in the cell layers of normal and transformed chondrocytes, a marked increase of these molecules in the culture media of the transformed cells was demonstrated. These findings were confirmed by experiments with temperature-sensitive mutants of the virus. PMID- 6267063 TI - T4 phage-coded dihydrofolate reductase. Subunit composition and cloning of its structural gene. AB - The structures of phage-coded dihydrofolate reductases are of interest because of 1) possible relationship to plasmid-coded dihydrofolate reductases; 2) unusual regulation of enzyme synthesis; and 3) multiple roles and intermolecular interactions involving the protein. To prepare for primary structural studies, we have cloned the T4 frd gene, which codes for dihydrofolate reductase, and we have determined for redetermined some physical properties of the enzyme. The native enzyme has a molecular weight of about 44,500, as determined by sedimentation velocity and gel filtration, and a subunit molecular weight of about 23,000, as determined by aminopterin titration and denaturing gel electrophoresis. We conclude that the enzyme is a dimer, with each subunit containing one methotrexate-binding site. A 1.1-kilobase pair fragment from a HindIII restriction digest of cytosine-substituted T4 DNA was cloned into pBR322, and recombinants were identified by trimethoprim resistance. Cells carrying this recombinant plasmid produce both the host cell and phage-coded dihydrofolate reductases. PMID- 6267064 TI - Transient state in the phosphorylation of sodium- and potassium- transport adenosine triphosphatase by adenosine triphosphate. AB - The rate of phosphorylation of sodium and potassium ion-transport adenosine triphosphatase by 10 microM [gamma-32P]ATP was much slower with Ca2+ than with Mg2+ (0.13-10 mM) in the presence of 16 to 960 mM Na+ at 0 degrees C and pH 7.4. In the presence of a fixed concentration of Mg2+ or Ca2+, the rate became slower with increasing Na+ concentration. When the Na+ concentration was fixed, the rate became slower with decreasing divalent cation concentration. Sodium ions appear to antagonize the divalent cation in the phosphorylation to slow its rate. In the presence of 1 mM Ca2+ and 126 or 270 mM Na+, the rate was slow enough to permit the manual addition of a chasing solution at various times before the phosphorylation reached the steady state. Therefore, we studied the time dependent change of the sensitivity to ADP or to K+ of the phosphoenzyme by a chase with unlabeled ATP containing ADP or K+ during the time range from the transient to the steady state of the phosphorylation. The ADP sensitivity decreased and the K+ sensitivity increased with the progress of the phosphorylation. With 270 mM Na+, the phosphoenzyme found at 1 s, when its amount was 5.5% of the maximum level, was virtually completely sensitive to ADP. Under these conditions, it was concluded that the form of the phosphoenzyme initially produced from the enzyme.ATP complex has ADP sensitivity and that the phosphoenzyme acquires K+ sensitivity later. The initially produced ADP-sensitive phosphoenzyme partially lost its normal instability and sensitivity upon adding a chelating agent, probably because of dissociation of a divalent cation from the phosphoenzyme. PMID- 6267065 TI - Functional interrelationship between (Na+ + K+)-ATPase and lysolecithin acyltransferase in plasma membranes of mitogen-stimulated rabbit thymocytes. PMID- 6267066 TI - Iron-sulfur N-1 clusters studied in NADH-ubiquinone oxidoreductase and in soluble NADH dehydrogenase. AB - Two N-1 type iron-sulfur clusters in NADH-ubiquinone oxidoreductase (Complex I, EC 1.6.5.3) were potentiometrically resolved: one was titrated as a component with a midpoint oxidation-reduction potential of -335 mV at pH 8.0, and with an n value equal to one; the other as an extremely low midpoint potential component (Em 8.0 less than -500 mV). These two clusters are tentatively assigned to N-1b and N-1a, respectively. Cluster N-1b is completely reducible with NADH and has a spin concentration of about 0.8/FMN. Its EPR spectrum can be simulated as a single rhombic component with principal g values of 2.019, 1.937, and 1.922, which correspond to the Center 1 reported earlier by Orme-Johnson, N. R., Hansen, R. E., and Beinert, H. (1974) J. Biol. Chem. 249, 1922-1927. At extremely low oxidation-reduction potentials (less than -450 mV), additional EPR signals emerge with apparent g values of gz = 2.03, gy = 1.95, and gx = 1.91, which we assign to cluster N-1a. It is difficult, however, to simulate the detailed spectral line shape of this component as a single rhombic component, suggesting some degree of protein modification or interaction with a neighboring oxidation-reduction component. EPR spectra of soluble NADH dehydrogenase, containing 5-6 g atoms of non-heme iron and 5-6 mol of acid-labile sulfide/mol of FMN, were examined. Signals from at least two iron-sulfur species could be distinguished in the NADH reduced form: one of an N-1b type spectrum; the other of a spectrum with g values of 2.045, 1.95, and 1.87 (total of about 0.5 spin equivalents/FMN). This is the first example of an N-1 type signal detected in isolated soluble NADH dehydrogenase. PMID- 6267067 TI - Stimulation of ATP-dependent proteolysis requires ubiquitin with the COOH terminal sequence Arg-Gly-Gly. AB - It was previously shown that ubiquitin is very similar to the polypeptide cofactor of the ATP-dependent protein degradation system from rabbit reticulocytes (Wilkinson, K. D., Urban, M. K., and Haas, A. L. (1980) J. Biol. Chem. 255, 7529-7532). We have extended this work to show that the peptic peptide maps are identical for bovine ubiquitin and the polypeptide cofactor isolated from human erythrocytes. It was noted however that ubiquitin preparations were less active in stimulating proteolysis than preparations of the polypeptide cofactor. This decreased activity has been shown to be due to the presence of an inactive form of ubiquitin in some preparations. The two forms of ubiquitin are separable by high performance liquid chromatography. The active form of ubiquitin has the COOH-terminal sequence -Arg-Gly-Gly at residues number 74 to 76. The inactive form terminates in -Arg74 as previously reported in the sequence studies of ubiquitin. Limited tryptic digestion of active ubiquitin yields the inactive, later eluting form and the dipeptide glycylglycine. This preteolytic cleavage apparently occurs during purification from most tissues. We thus propose reserving the term ubiquitin for the intact 76-amino acid sequence and designating the 74-amino acid sequence as ubiquitin-t to indicate its derivation by a tryptic-like protease cleavage. This 76-residue sequence is consistent with the covalent structure of protein A-24, a conjugate where carboxyl group of the COOH-terminal glycylglycine of ubiquitin is linked by an amide bond to the epsilon-amino group of Lys-119 of histone H2A. Thus, the structural requirements of the protein and ubiquitin molecules are identical for formation of protein A 24 and for forming the covalent conjugates thought to be intermediates in ATP dependent protein degradation. PMID- 6267069 TI - Detergent solubilization of the formyl peptide chemotactic receptor. Strategy based on covalent affinity labeling. AB - The formyl peptide chemotactic receptor has been solubilized by digitonin treatment of purified human neutrophil membranes. Of several potential assay methods tested for their ability to separate receptor-bound from free ligand, only gel filtration through an acrylamide cross-linked agarose matrix yielded satisfactory results. Approximately 70% of the receptor initially present in the membrane was recovered in the digitonin extract. Binding of 125I-labeled N-formyl Nle-Leu-Phe-Nle-Tyr-Lys to the soluble receptor was rapid (t 1/2 at 22 degrees C less than 5 min), of high affinity (Kd = 2.2 nM) and saturable. The relative potencies of a small series of peptides as inhibitors of binding to the soluble receptor paralleled their potencies as inhibitors of the membrane-bound receptor. N-Formylation of the peptides was required for high affinity binding. Binding was maximal at pH 6.5 and was sulfhydryl-dependent; 20 microM p chloromercuriphenylsulfonic acid decreased binding by 50%. 125I-labeled N-formyl Nle-Leu-Phe-Nle-Tyr-Lys was specifically cross-linked to the soluble receptor with ethylene glycol bis(succinimidyl succinate) and an apparent molecular weight of 55,000 to 70,000 and determined for the soluble receptor by sodium dodecyl sulfate polyacrylamide gel electrophoresis. A strategy for obtaining an active, detergent-soluble receptor preparation based on covalent affinity labeling is presented. PMID- 6267068 TI - Purification and properties of the Escherichia coli protein factor required for lambda integrative recombination. AB - A purified preparation of the Escherichia coli integration host factor (IHF) displays two polypeptides of apparent molecular weight 11,000 and 9,500 when analyzed by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Under nondenaturing conditions, IHF appears to exist as a 1:1 complex of these two polypeptides. Integrative recombination takes place in vitro when purified IHF and purified Int, a product of a bacteriophage lambda gene, are the only proteins added to reaction mixtures. No recombination is detected in the absence of either protein. The characteristics of the recombination reaction carried out by these two purified proteins are described. Purified IHF binds to DNA; in the presence of Int, a ternary complex is formed at one of the specific recombination sites. IHF hs no detectable endonuclease or topoisomerase activity. Several possibilities for the role of IHF in recombination are considered. PMID- 6267070 TI - Methionyl-tRNA synthetase-induced conformational change of Escherichia coli tRNAfMet. AB - Ribonuclease T2, nuclease S1, and snake venom phosphodiesterase were used as a structural probe for investigation of the interaction between Escherichia coli tRNAfMet and methionyl-tRNA synthetase, and the cleavage sites were analyzed by a rapid sequencing gel electrophoresis of 5'-32P-labeled tRNA. Both endonucleases cleaved the D-loop of synthetase-bound tRNA much more extensively than that of the free tRNA. Positions of A14, G15, A22, and G23 in the D-loop and C35 in the anticodon of the synthetase-bound tRNA were more susceptible to RNase T2. The synthetase-bound tRNA was predominantly cleaved by nuclease S1 at position of G15, G19, G20, and G23 in the D-loop and G2 in the acceptor stem. In contrast, the synthetase-bound tRNA was more resistant to the 3'-exonuclease, snake venom phosphodiesterase, than was the free tRNA molecule. These results suggest conformational change of the tRNA by the synthetase binding which weakened tertiary interaction between the D-loop and T psi C-loop/extra-loop. Production of acid-soluble radioactivity was also examined in the limited digestion of 5' 32P-labeled tRNA or 3'-14C-labeled methionyl-tRNA. The synthetase enhanced the release of acid-soluble oligonucleotides from the 5'-end of the tRNA but suppressed that from the 3'-end of the molecule. These results are consistent with that obtained by gel electrophoresis. PMID- 6267071 TI - A homogeneous type II DNA topoisomerase from HeLa cell nuclei. AB - Using kinetoplast DNA networks as a substrate in a decatenation assay, we have purified to apparent homogeneity a type II DNA topoisomerase from HeLa cell nuclei. The most pure preparations contain a single polypeptide of 172,000 daltons as determined by sodium dodecyl sulfate-gel electrophoresis. The molecular weight of the native protein, based on sedimentation and gel filtration analyses, is estimated to be 309,000. These results suggest that the enzyme is a dimer of 172,0090-dalton subunits. The enzyme is a type II topoisomerase as demonstrated by its ability to change the linking number of DNA circles in steps of two and to decatenate or unknot covalently closed DNA circles. No gyrase activity is detectable. ATP is required for the relaxation, decatenation, and unknotting of DNA, and a DNA-dependent ATPase activity is present in the most pure fractions. ATP is hydrolyzed to ADP in this properties to T4 DNA topoisomerase (Liu, L. F., Liu, C. C., and Alberts, B. M. (1979) Nature 281, 456 461). PMID- 6267072 TI - Restriction and modification in Bacillus subtilis: two DNA methyltransferases with BsuRI specificity. I. Purification and physical properties. AB - Two S-adenosyl-L-methionine:DNA (cytosine 5)-methyltransferases, termed M.BsuRIa and M.BsuRIb, were purified 3,000- and 4,000-fold, respectively, from Bacillus subtilis strain OG3R (r+m+) by successive column chromatography. The molecular weights determined by gel filtration were 37,000 for M.BsuRIa and 40,000 for M.BsuRIb. The sedimentation coefficients s20,w were 3.55 for both enzymes as determined by glycerol gradient centrifugation, corresponding to molecular weights of 43,000. Analysis of the two methyltransferases by agarose gel electrophoresis under native conditions, followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis, showed correspondence of the M.BsuRIa activity with one protein band at a molecular weight of 41,000, whereas M.BsuRIb activity was associated with two protein bands with molecular weights of 42,000 and 39,000, respectively. PMID- 6267073 TI - Restriction and modification in Bacillus subtilis: two DNA methyltransferases with BsuRI specificity. II. Catalytic properties, substrate specificity, and mode of action. AB - The properties of two DNA methyltransferases, termed M. BsuRIa and M. BsuRIb, whose isolation was described in the preceding paper (Gunthert, U., Freund, M., and Trautner, T. A. (1981) J. Biol. Chem. 256, 9340-9345) were compared. Both enzymes recognize the same target sequence in double-stranded DNA, leading to methylation of the internal cytosine: 5'GGCC. The enzymes have identical reaction constants with their substrates, DNA (km = 2.7 nM for the 5' GGCC sequence), and S-adenosyl-L-methionine (km = 0.7 microM). Initial rates of methyl group transfer were proportional to enzyme concentration over a range of 50-fold, indicating absence of aggregation. The enzymes are different in their ionic strength requirements using Tris-HCl, pH 8.4. M. BsuRIa is most active at 100 mM, M. BsuRIb at 440 mM. As measured by incorporation kinetics and heat inactivation, M. BsuRIa is the more stable enzyme of the two. Equilibrium dialysis was used to study the mode of methyl group transfer to the DNA with either enzyme. The data indicate that initially S-adenosyl-L-methionine binds to methyltransferase. This complex attaches to either modified or nonmodified DNA. The methyl group will then be transferred to a nonmodified target sequence, leading to the dissociation of enzyme and S-adenosyl-L-homocysteine from the DNA. PMID- 6267074 TI - Further analysis of the polypeptide subunits of yeast cytochrome c oxidase. Isolation and characterization of subunits III, V, and VII. AB - By using a modified purification procedure in which we have substituted detergent exchange gel filtration for DEAE-cellulose or hydroxylapatite chromatography (Mason, T. L., Poyton, R. O., Wharton, D. C., and Schatz, G. (1973) J. Biol. Chem. 248, 1346-1354), we have isolated yeast cytochrome c oxidase preparations which are low in contaminating polypeptides and which have been successfully used for the large scale purification of subunits. Subunits have been purified from this preparation by a simple two-step procedure which involves: 1) the release of subunits IV and VI from an "insoluble" core composed of subunits I, II, III, V, and VII; and 2) gel filtration of the "core" subunits in the presence of sodium dodecyl sulfate. Molecular weights of the isolated subunits, obtained from sodium dodecyl sulfate gel retardation coefficients (KR) derived from Ferguson plots, were: I, 54,000; II, 31,000; III, 29,500; IV, 14,500; V, 12,500; VI, 9,500; VII, 4,500. In their purified state all subunits, except for subunit V, exhibited electrophoretic behavior similar to that exhibited by unpurified subunits in sodium dodecyl sulfate-dissociated holoenzyme preparations. As purified, subunit V exhibits a slightly smaller apparent molecular weight than its counterpart in the holoenzyme. Amino acid analysis of the isolated subunits revealed that subunit III, a mitochondrial translation product, contained 41.9% polar amino acids, whereas subunits V and VII, cytoplasmic translation products, each contained 47.7% polar amino acids. These results extend and support our previous finding that the mitochondrially translated subunits of yeast cytochrome c oxidase are more hydrophobic than the cytoplasmically translated subunits. PMID- 6267075 TI - Glomus tumours of the coccygeal body associated with coccydynia. A preliminary report. AB - Two cases of coccydynia are presented. Their definitive treatment was excision of the coccyx and the pericoccygeal tissues. The histology in both cases revealed a glomus tumour of the coccygeal body and the symptoms were completely relieved after operation. Glomus tumours of the coccygeal body may be the cause of some cases of coccydynia. PMID- 6267077 TI - The effect of polyoma virus, serum factors, and dibutyryl cyclic AMP on dihydrofolate reductase synthesis, and the entry of quiescent cells into S phase. AB - Three procedures were used to induced dihydrofolate reductase synthesis in quiescent cultures of methotrexate resistant mouse fibroblasts: 1) lytic infection with polyoma virus, 2) growth stimulation by replating cells at lower density in fresh cell culture medium, and 3) the addition of fresh medium to confluent cells. Following polyoma infection, an increase in the percentage of S phase cells began at approximately 20 hours; dihydrofolate reductase synthesis also increased following a lag of 20 hours or more, and continued to increase throughout the late phase of lytic infection, reaching values nearly fivefold greater than that originally present in the quiescent cells. When quiescent cells received fresh medium (with or without replating), the percentage of cells in S phage began to increase by 10 hours and was accompanied by an increase in dihydrofolate reductase synthesis which reached a maximum by approximately 25 hours. These observations show that the initial entry of cells into S phase following mitogenic stimulation is associated with an induction of dihydrofolate reductase synthesis. Dibutyryl cyclic AMP blocked the stimulation of dihydrofolate reductase synthesis and the increase in the percentage of S-phase cells that resulted from the addition of fresh medium to confluent cells. When dibutyryl cyclic AMP was added at various times following the addition of fresh medium, the block in the induction of dihydrofolate reductase synthesis was correlated with a corresponding block in the increase in S-phase cells. These results suggest that dibutyryl cyclic AMP blocks cells at a point in G1 prior to either the induction of dihydrofolate reductase synthesis of the beginning of S phase. The relationship between the control of dihydrofolate reductase synthesis and entry into S phase suggests some form of coordinate control over these two parameters. PMID- 6267076 TI - T- and B-cell determination in various lymphoid tissues of mice during N nitrosobutylurea (NBU) leukemogenesis. AB - T- and B-cell distribution in thymus, spleen, and lymph nodes has been investigated during chemical lymphomagenesis. N-nitrosobutylurea (0.04 g/100 ml) in drinking water was administered to 35-day-old male C57BL mice for a period of 60 days. As of week 11, 21 of 22 Nbu mice developed thymic lymphomas of lymphoblastic cell type which showed a general leukemic spread to spleen, lymph nodes, and several extralymphatic organs at week 16. Immunocytologic studies revealed the T-cell origin of these thymic type lymphomas. Alteration of the T cell system during latency period was represented by reduced thymic weight, cell numbers, as well as absolute and relative T-cell reduction. Absolute T-cell reduction was also observed in the spleen, although the reduction of splenic lymphoid cells was mainly caused by a decrease of B cells. In lymph node subnormal variations of theta-positive cells took place, whereas B-cell distribution was not altered. An impaired T- and B-cell function was suspected from preleukemic changes of lymphoid subpopulations. The results are compared with other murine lymphomas and discussed with regard to a functional hypothesis of lymphomagenesis. PMID- 6267078 TI - Localization and characterization of N-ethylmaleimide sensitive inhibitor(s) of thiol cathepsin activity from cultured nil and polyoma virus-transformed nil hamster cells. AB - Exposure of cultured Nil (a stable line of fibroblast cells from Syrian hamsters) or polyoma virus-transformed (PyNil) hamster fibroblasts to 0.5 mM N ethylmaleimide for 5 minutes resulted in striking increases in thiol cathepsin activity in unfractionated cell-free lysates. The paradoxical increase in activity of the normally N-ethylmaleimide-sensitive cathepsins apparently occurred as the result of the protective compartmentalization of the cathepsins in the lysosomes (20,000 X g sedimented fraction) and the unprotected localization of an inhibitor(s) in the soluble cytoplasm (175,000 X g supernatant fraction). Under continuous exposure of the cells to N-ethylmaleimide, a rapid increase in cathepsin activity (seen in the first 5 minutes) was followed by a steady decrease in activity (half inactivation time, 90 minutes). The relative difference in rates of N-ethylmaleimide inactivation of thiol cathepsins and thiol cathepsin inhibitors provides a means for estimating lysosomal cathepsin activity in whole cell extracts without the need for more time-consuming fractionation procedure. In reciprocal inhibition tests, it was found that, regardless of the source of cathepsins, the Nil and PyNil cathepsin inhibitor(s) inactivated the cathepsins to approximately the same extent. The inhibitors were heat stable (90-100 degrees C for 15 minutes) at pH 4, but were totally inactivated when boiled at pH 8.5. On a calibrated Sephadex G-100 column, the relative molecular weight (Mr) of the inhibitor(s) was 13,000 daltons. On the same column, the Mr of the cathepsins was 24,000 daltons. Compared with the cathepsin activity from Nil cells, there was about five times less cathepsin activity recoverable from the PyNil cells. PMID- 6267079 TI - Distinctive effects of hydrocortisone on the modulation of EGF binding and cell growth in HeLa cells grown in defined medium. AB - Hydrocortisone modulates the binding capacity of HeLa cells for 125I-labeled epidermal growth factor (EGF). A twofold increase in 125I-labeled EGF binding is observed within 24 hours after the addition of pharmacological concentration of hydrocortisone (5 X 10(-8) - 1 X 10(-6) M). This enhancement of binding is reversible, and occurs when the cells are cultured in either serum-supplemented or completely defined, serum-free, hormone-supplemented medium. Scatchard analysis of the binding data indicates that the number of 125I-EGF binding sites is increased, and that no appreciable change in the affinity of the EGF receptor for labeled EGF occurs. In the serum-free condition hydrocortisone stimulates the growth of HeLa cells, but we have observed no connection between this growth stimulation and the enhancement of EGF binding. The growth response to hydrocortisone is independent of EGF, and the concentration dependency of the growth response to EGF is unaltered by the addition of hydrocortisone to the medium. Hydrocortisone elicits the growth response at a concentration as low as 5 X 10(-9) M, while a concentration higher than 5 X 10(-6) M is required to affect the binding capacity for 125-EGF. These effects are specific for glucocorticoid steroids. Similar concentrations of progesterone, testosterone, or estradiol produce no measurable response. Although the elevation of EGF receptor levels in the serum-supplemented medium is similar to that observed in the serum-free cultures, hydrocortisone is growth-inhibitory under these conditions. This growth inhibition occurs at pharmacological concentrations of hydrocortisone with a concentration dependency that is similar to that of the EGF receptor modulation. PMID- 6267080 TI - Gonadotropin stimulation of pregnenolone metabolism in Chinese hamster ovary cells in culture. AB - To determine if Chinese Hamster Ovary (CHO) cells in culture are able to metabolize steroids, CHO cells were incubated in defined medium with [14C]pregnenolone. As shown, [14C]pregnenolone is metabolized to progesterone and other delta 53 beta steroids; this steroidogenic response is appreciably enhanced upon exposure of the cells to 50 nM gonadotropins (human chorionic gonadotropin and follicle-stimulation hormone). The primary metabolites that accumulate in the medium upon treatment with gonadotropins are 16 alpha-hydroxy-pregnenolone and 16 alpha-17 beta-dihydroxydehydroepiandrosterone. Exposure of the CHO cells to gonadotropins induces significant increases in the activities of 16 alpha hydroxylase, 17 alpha-hydroxylase, and 17-20 lyase. Similar results are obtained when the CHO cells are treated with 0.1 mM 8-bromocyclic AMP, indicating that the gonadotropin enhancement of steroid metabolism is a cyclic AMP-mediated process. CHO cells apparently lack the cholesterol desmolase complex since 14C-cholesterol is not utilized by these cells to produce other steroid metabolites. These results indicate that CHO cells offer an in vitro system for the study of certain aspects of gonadotropin stimulation of steroidogenesis. PMID- 6267081 TI - The activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase and the rate of sterol synthesis diminish in cultures with high cell density. AB - The specific activity of HMG-CoA reductase, the major rate-limiting enzyme in the sterol biosynthetic pathway, declined linearly with increasing cell density in four different lines of mammalian cell cultures. As expected, this caused the rates of sterol synthesis from [14C]acetate to decline in a parallel manner. The decrease in reductase activity in the dense cultures was also correlated with decreased incorporation of [14C]acetate into fatty acids and [3H]thymidine into DNA. In contrast, the activities of two enzymes, NADH dehydrogenase and 5' nucleotidase, which are not involved in lipid synthesis, were independent of changes in cell density. The simplest explanation for these data is tht HMG-CoA reductase and the synthesis of sterol and fatty acids are regulated in concordance with the rate of cell growth and proliferation. PMID- 6267083 TI - Multihormonal regulation of ornithine decarboxylase activity in highly differentiated porcine granulosa cells in vitro. AB - Purified luteinizing hormone, but not follicle-stimulating hormone, elicited time and dose-dependent stimulation of the cytosolic enzyme, ornithine decarboxylase, in highly differentiated, porcine granulosa cells maintained in vitro in chemically defined medium. Enzymatic induction was susceptible to inhibitors of protein and RNA synthesis, and was suppressed by selective direct and indirect inhibitors of ornithine decarboxylase. Physiologic concentrations of prostaglandin E2 and L-epinephrine also enhanced enzymatic activity in a dose dependent and saturable manner. Systematic comparison of the hormonal induction of ornithine decarboxylase in highly differentiated versus poorly differentiated granulosa cells revealed distinctive patterns of enzymic responsivity in relation to the degree of cytodifferentiation attained in vivo. This in vitro model is likely to permit further detailed examination of the molecular mechanisms subserving the hormonal control of ovarian ornithine decarboxylase activity in spontaneously differentiated granulosa cells maintained under chemically defined conditions in vitro. PMID- 6267082 TI - Cyclic AMP-dependent protein kinases from Balb 3T3 cells and other 3T3 derived lines. AB - Cyclic AMP-dependent protein kinase and 3H-cAMP-binding activities were determined in normal Balb 3T3 cells and compared with the same preparations from SV40, chemical, and spontaneous transformants of 3T3 cells. The cytosolic protein kinase activities and protein kinase activity ratios were similar in all cell lines, although when the normal 3T3 cytosol was prepared by homogenization it contained less 3H-cAMP binding activity than the transformed 3T3 cytosols. The Triton X-100 treated particulate fractions from the normal and transformed 3T3 cells contained similar protein kinase and binding activities. The isozymic profile of cAMP-dependent protein kinases was examined by DEAE-chromatography. The 3T3 cells contained only type II isozyme in either cytosolic or membrane fractions. All transformants of the 3T3 cells contained both type I and type II isozymes. Other cell cultures, including chicken embryo fibroblasts, rat kidney cells, and human or calf endothelial cells contained type I and type II isozymes. Binding of the photoaffinity analogue of cAMP, 8-N3 cAMP, to the regulatory subunits of protein kinases in sonicates obtained from Balb 3T3 and SV 3T3 cells followed by separation on SDS polyacrylamide electrophoresis showed that the amount of RII subunit was approximately equal in the two cell lines. RI in Balb 3T3 cells was detectable but in a much lower quantity than in SV 3T3 cells. The cyclic AMP dependent-protein kinases from Balb 3T3 cells appears to be different from SV 3T3 cells by three criteria: 3H-cAMP binding in homogenates, DEAE chromatographic separation of isozymes, and 8-N3 cAMP binding. PMID- 6267084 TI - Effect of aminonucleoside on transcription, methylation, and maturation of ribosomal RNA in SV40-transformed human lung fibroblasts. AB - The effects of puromycin aminonucleoside (AMS) have been studied in the nucleoli of SV40-transformed human lung fibroblasts with attention to the relationship between transcription, methylation, and maturation of ribosomal RNA (rRNA). Inhibition of the transcription of pre-rRNA became evident between 1 and 2 hr of exposure to AMS, and the degree of inhibition remained approximately constant throughout the remainder of the 18-hr period of study. Methylation of the ribose units of pre-rRNA was inhibited by AMS approximately as much as RNA transcription, but later, suggesting that the inhibition of methylation is a consequence of the lowered rate of RNA transcription. It was also noted that ribose methylation of nucleolar RNA occurs in the absence of concurrent RNA transcription, indicating that rRNA may be methylated post-transcriptionally. Exposure of the fibroblasts to fresh serum had the capacity to increase the rate of nucleolar RNA transcription if the fibroblasts were treated with AMS for periods of less than 2 hr but was ineffective thereafter, confirming that the inhibitory effect of AMS on pre-rRNA transcription is established in approximately 2 hr. On the other hand, processing of the primary transcript (45 S RNA) to the mature rRNA species (28 and 18 S) was inhibited more gradually, with a complete inhibition of rRNA maturation being noted after 18 hr of AMS treatment. These data are consistent with the view that the primary effect of AMS is on the rate of rRNA transcription, with a later effect on its maturation, while RNA methylation is reduced only because of the diminished availability of the RNA substrate. PMID- 6267085 TI - Sodium fluxes in human fibroblasts: kinetics of serum-dependent and serum independent pathways. AB - Sodium influx in serum-deprived human fibroblasts is by way of a pathway which shows saturation kinetics. A plot of initial Na influx versus [Na]0 ([Na]i approximately equal to 10 mM) gives a simple Michaelis-Menten type of curve with a K1/2 = 70.0 +/- 8.1 mM and a Vmax = 14.5 +/- 1.9 mumol/g prot/min. A similar plot of initial Na influx versus [Na]0 in the presence of 10% fetal bovine serum (FBS) gives a nonsaturating curvilinear response which appears to be biphasic. A plot of the serum-dependent Na influx versus [Na]0 (obtained by subtracting the curve in the absence of FBS from the curve in the presence of 10% FBS) shows that there is a linear relationship between serum-induced Na influx and external [Na]. At physiological Na concentrations, in the presence of FBS, the serum-induced Na influx is equal to the amiloride-sensitive Na flux, whereas in the absence of serum amiloride inhibits less than 10% of the Na influx. The effect of intracellular Na on Na flux was tested by preloading cells with Na in a digitoxin containing medium prior to measurement of Na flux. A plot of steady-state Na exchange flux versus [Na]0 ([Na]i approximately equal to [Na]0) in the absence of serum gives a curve that appears to saturate at approximately 100 mM Na (flux = 100 mumol/g prot/min) and then declines with increasing [Na] (flux = 40 mumol/g prot/min at 150 mM). In contrast to Na influx in control serum-deprived cells, Na flux in Na-loaded cells in dramatically inhibited by the presence of amiloride. Since the peak Na exchange flux of 100 mumol/g prot/min is greatly in excess of the Vmax for Na influx in control serum-deprived cells and the enhanced Na flux is amiloride-sensitive, elevating intracellular Na must somehow activate the amiloride-sensitive Na transport system, which is normally only minimally active in the absence of serum. PMID- 6267086 TI - The binding and processing of plasminogen by Balb/c 3T3 and SV3T3 cells. AB - The binding and processing of plasminogen by Balb/c 3T3 and SV3T3 cells was studied using 125I-labeled canine plasinogen. Throughout a 3-day period, 125I plasminogen in the incubation medium bound to the cells and was degraded, first to intermediate-sized macromolecules that were the same size as the large (74,600 dalton) and small (25,000-dalton) chains of active plasmin, and to smaller fragments including 3-iodo-L-tyrosine. Binding to SV3T3 cells was independent of the protease-dependent morphological change (PDMC) characteristic of these and many other transformed cells. The SV3T3, and to a somewhat lesser extent, the 3T3 cells, both accumulated and released into the incubation medium 3-iodo-L tyrosine, a terminal lysozymal digestion product. The results of a sublethal cell surface trypsinization assay suggest that the cell-associated plasminogen was primarily bound to the surfaces of the 3T3 and SV3T3 cells while the macromolecular degradation products including active plasmin were inside the cells. The rate of 125I plasminogen degradation exhibited by SV3T3 cells was approximately two time greater than that of 3T3 cells, which presumably reflects differences in endocytosis or lysosomal hydrolysis, or both. The rates were unaffected by addition of pancreatic or soybean trypsin inhibitor sufficient to inhibit PDMC. In the incubation medium, plasminogen was activated to plasmin by SV3T3, but not by 3T3 cells. However, 95-100% of plasmin covalently bound to a 47,000-dalton canine serum component, which could be dissociated from plasmin by hydroxylamine: 95-100% of the plasmin was inactive to reaction with DF32P. Thus the serum component is a plasmin inhibitor. The plasmin-containing complex in the medium had an apparent molecular weight of 212,000. Under denaturing conditions, the complex dissociated into two covalently modified plasmin-containing species of 153,000 and 127,000 daltons. In addition to forming a complex with a serum component, the plasmin is cleaved into two small fragments (approximately 10,000 and 12,000 daltons) by as-yet uncharacterized serum factors. PMID- 6267087 TI - Membrane particle arrays in SV40-transformed 3T3 cells. AB - The ultrastructural organization of the plasma membrane of untransformed and simian virus (SV)40-transformed 3T3 cells in culture was studied by an in situ freeze-fracturing technique. Both 3T3 and SV3T3 cells showed randomly distributed intramembrane particles as well as gap junctions. In addition, the plasma membrane (P-face) of confluent SV40-transformed 3T3 cells was found to display a unique membrane specialization which was not observed in normal 3T3 cells. This membrane specialization consisted of irregularly-shaped arrays of loosely dispersed large (11-12 nm) intramembrane particles, located in regions of close contact between adjacent SV3T3 cells. When a P- to E-fracture face transition occurred within the boundaries of a particle array, the intracellular space appeared uniformly reduced and arrays of pits coextensive with the P-face particles could be recognized on the E-face. Particle arrays appeared particularly prominent in SV3T3 cells grown in the presence of high serum concentrations (20% foetal calf serum or calf serum). Particle arrays resembling those found in SV3T3 cells were observed only in very rare instances in the plasma membrane of other virus-transformed cell lines. Several possible interpretations of the meaning of the particle arrays, including the hypothesis thay they represent an unusual or abortive form of intracellular junction, are discussed. The absence of similar membrane specializations in the plasma membrane of untransformed 3T3 cells points to a difference in membrane organization and cell contact ultrastructure between normal and SV40-transformed 3T3 cells. PMID- 6267088 TI - Inorganic phosphate accumulation and phosphatase activity in the nucleus of maize embryo root cells. AB - The nucleus of growing root cells Zea mays contains a high concentration of inorganic phosphate. In order to verify whether this high nuclear Pi concentration is correlated with the metabolic activity of the nucleus, the Pi has been visualized in root cells of maize embryos at the electron-microscope level during 2 different periods which are both characterized by a spectacular reactivation of the nuclear metabolism, i.e. the early germination and the period of recovery following a thermal treatment given to the seeds after 48 h of germination. In both situations the Pi concentration increased in the nucleus during its reactivation. To verify whether the high nuclear Pi concentration could be of endogenous origin, the phosphatase activities were measured in crude extracts of root tissues during nuclear reactivation. The specific activity was optimal at pH 4.5 and was shown to increase with cellular reactivation. The ultrastructural localization of acid phosphatase activity showed that Pi may be produced at 3 distinct sites: plasmalemma, vacuoles and most probably nucleus itself. High acid phosphatase activities were found in nuclei displaying a high metabolism. Taking these results and previous data into account, we suggest that a correlation may exist between the rate of nuclear transcription, the level of nuclear acid phosphatase activity and the nuclear Pi accumulation. PMID- 6267089 TI - Separation of cytochromes c by reversed-phase high-performance liquid chromatography. AB - Six kinds of cytochrome c of different origin, i.e., bovine, chicken, dog, horse, rabbit and tuna, were subjected to separation by reversed-phase high-performance liquid chromatography on three commercial packing materials; octadecyl-, octyl- and cyanoalkyl-silicas. The effects of reversed-phase material, mobile phase and temperature on the separation of cytochromes c were examined. The parameters of the mobile phase were the organic modifier, the pH, the salt concentration and additives. Under optimal conditions, five of the six cytochromes c were resolved in 10 min. The relative retention values cannot be explained in terms of the relative lipophilicities of the side-chains of the amino acid residues. PMID- 6267090 TI - Enzymatic detection of urinary acidic 3 alpha-hydroxysteroids on thin-layer chromatograms. PMID- 6267091 TI - Electron microscopy in the routine screening of newborns with congenital cytomegalovirus infection. AB - The pseudoreplica method of electron microscopy (EM) was evaluated as a rapid screening technique for the detection of cytomegaloviruria in 3056 neonates in a predominantly lower socioeconomic population. Virus isolation methods detected 49 (1.6%) CMV-positive individuals. When pools of three to five urines were tested, 26 (54%) of the culture-positive neonates were identified by EM; however, testing of individual urines increased EM detection to 33 (67%). Almost all of these urines, as well as urine or oral specimens obtained on follow-up visits, which had infectivity titers greater than or equal to 10(4)/ml were EM-positive, whereas only half of the specimens with titers less than 10(4)/ml were EM positive. All the symptomatic neonates were detected by EM, suggesting that electron microscopy would be most valuable as a diagnostic aid in this group of CMV-infected neonates. PMID- 6267092 TI - Transformation of canine kidney cells by SV40. PMID- 6267093 TI - ELISA for the detection and quantification of C-type viral glycoprotein (gp70) using antibodies that recognize the protein moieties of the glycoproteins. AB - The enzyme-linked immunosorbent assay (ELISA) technique was applied to the detection and quantification of simian sarcoma-associated virus (SiSV) glycoprotein gp70 in virus preparations and cells and compared to the RIA competition technique. By detecting 0.1 ng of retroviral glycoprotein, its sensitivity is comparable to that of the RIA technique. It was further shown that the antibodies used recognize the protein and not the sugar components of the glycoprotein. PMID- 6267094 TI - Rapid identification of viruses by a simple indirect immune electron microscopy technique using ferritin-labelled antibodies. PMID- 6267095 TI - Cloning of hepatitis A virus genome. AB - Hepatitis A virus (HAV) was highly purified from faeces. The genomic RNA was transcribed to cDNA and this DNA was then cloned into plasmid pBR 322 at the Pst I site, and clones were selected in presence of tetracycline. Most clones contained inserts which hybridized to HAV-specific RNA isolated from HAV-infected cell cultures derived from a human hepatocellular carcinoma. Two clones expressed low amounts of viral antigens. PMID- 6267097 TI - Topographical heterogeneity of basal and thyrotropin-stimulated adenosine 3'5' monophosphate in human nodular goiter. PMID- 6267096 TI - Multiple forms of human tumor calcitonin demonstrated by denaturing polyacrylamide gel electrophoresis and lectin affinity chromatography. PMID- 6267098 TI - Plasma calcitonin as a marker of disease activity in patients with small cell carcinoma of the lung. AB - To evaluate the usefulness of plasma calcitonin as an index of tumor burden and disease activity, we undertook a prospective study of serial calcitonin measurements in a group of patients with small cell carcinoma of the lung from diagnosis throughout a period of intensive therapy. Plasma calcitonin was significantly elevated in 84% of patients with extensive small cell carcinoma of the lung and was not elevated in patients with limited disease at the time of diagnosis. The elevated values fell significantly in response to chemotherapy and radiation therapy, and reflected regression of followable disease and improvement in clinical status. A significant correlation existed between plasma calcitonin and extent of disease. Relapse was generally associated with an increase in elevated plasma calcitonin levels, and calcitonin appeared to reflect tumor burden. The serial measurement of plasma calcitonin is useful in the management of the patient with small cell carcinoma of the lung. PMID- 6267099 TI - Fibroblast defect in pseudohypoparathyroidism, type I: reduced activity of receptor-cyclase coupling protein. AB - Erythrocytes of many patients with pseudohypoparathyroidism, type I (PHP-I), exhibit reduced activity of the N protein, a guanine nucleotide-binding regulatory component of hormone-sensitive adenylate cyclase. We compared N and adenylate cyclase activities and the accumulation of cAMP in fibroblasts propagated from skin biopsies of six normal subjects and seven PHP-I patients. N activities were reduced by approximately 40% in fibroblasts as well as erythrocytes of five PHP-I patients. N activities in fibroblasts from two PHP-I patients with normal erythrocyte N activities were within the normal range. These results are consistent with the hypothesis that N deficiency is generalized in tissues of most PHP-I patients and is the primary defect responsible for their resistance to metabolic effects of hormones that work by stimulating adenylate cyclase. Fibroblast N deficiency was not associated with decreases in hormone stimulated adenylate cyclase or cAMP accumulation in fibroblasts, probably because these activities involve many potentially regulable cellular components in addition to the N protein. PMID- 6267100 TI - Physiologic concentrations of normal human plasma lipoproteins inhibit the immortalization of peripheral B lymphocytes by the Epstein-Barr virus. AB - Epstein-Barr virus (EBV)-induced immortalization of adult human B lymphocytes is suppressed by physiologic concentrations of human plasma lipoproteins. Several inhibitory mechanisms appear to be operative. First, low density lipoproteins (LDL) directly reduce the ability of EBV to transform human B cells. Second, LDL as well as intermediate and very low density lipoproteins modulate early inductive events rendering the B cell refractory to transforming signals from EBV. Third, LDL also selectively inhibit an EBV-inducible step that occurs within 24 h after transformation. Finally, very low density lipoproteins can abrogate the ongoing, cellular proliferation of EBV-transformed, established B cell lines. The plasma lipoproteins may therefore prevent the emergence of EBV-transformed malignant B cell clones in vivo. Conceivably, on this basis, environmental and genetic influences on plasma lipoprotein concentrations may affect the global distribution of Burkitt's lymphoma, a lymphoid malignancy putatively caused by EBV. PMID- 6267101 TI - Oxidative decarboxylation of free and peptide-linked amino acids in phagocytizing guinea pig granulocytes. AB - The oxidative decarboxylation of amino acids by a system consisting of myeloperoxidase-hydrogen peroxide-chloride has been demonstrated previously by others and the process has been considered to be part of the microbicidal armamentarium of some phagocytic leukocytes. We were able to translate these earlier observations, made on model systems, to intact guinea pig granulocytes. We could demonstrate differences in the cellular handling of peptide-linked amino acids as particles, compared with free amino acids. Specific inhibitors were used to explore two routes of oxidative decarboxylation: (a) the myeloperoxidase catalyzed direct decarboxylation-deamination reaction, and (b) oxidation of alpha keto acids after transamination of amino acids. These inhibitors were cyanide, azide, and tapazole for the former pathway, and amino-oxyacetate for the latter. Amino-oxyacetate profoundly inhibited the decarboxylation of free 14C-amino acids (alanine and aspartate) in both resting and stimulated cells, but had only a minimal effect on 14CO2 production from ingested insoluble 14C-protein. On the other hand, the peroxidase inhibitors cyanide, azide, and tapazole dramatically inhibited the production of 14CO2 from ingested particulate 14C-protein, but had only small effects on the decarboxylation of free amino acid. Soluble, uniformly labeled 14C-protein was not significantly converted to 14CO2 even in the presence of phagocytizable polystyrene beads. These observation suggest that the amino acids taken up by phagocytosis (e.g., as denatured protein particles) are oxidatively decarboxylated and deaminated in the phagosomes by the myeloperoxidase-hydrogen peroxide-chloride system; soluble free amino acids that enter the cytoplasm by diffusion or transport are oxidatively decarboxylated after transamination by the normal cellular amino acid oxidative pathway. PMID- 6267102 TI - 125I-8-L-arginine vasopressin binding to human mononuclear phagocytes. AB - The binding of vasopressin to human circulating blood cells was examined. Direct binding studies with preparations of single cell types indicated that the mononuclear phagocyte system is almost entirely responsible for binding of the hormone. Binding of 125I-8-L-arginine vasopressin (AVP) (40 pM) in the presence of excess unlabeled hormone was saturable (2.8 +/- 0.4 fmol/2 x 10(6) cells per ml), was linear with cell number, was dependent upon the concentration of the radioligand used, and was reversible. Binding equilibrium was achieved in 30--40 min at 22 degrees C. Scatchard analysis of binding at this time showed an apparent dissociation constant of 25 +/- 0.21 pM, providing an estimate of 640 +/ 80 sites/cell. Pretreatment of the cells with cytochalasin B, an agent that can block phagocytosis, did not modify radioligand binding, which indicates that 125I AVP uptake by the cells is due to binding and not to endocytosis. Specificity of vasopressin-sensitive sites on mononuclear phagocytes was demonstrated with a series of vasopressin analogues with various degrees of antidiuretic potency, and with peptide hormones that bind to specific receptors on circulating blood cells but that lack antidiuretic activity. AVP (40 pM) elevated the intracellular level of cyclic AMP from 137 +/- 8.6 to 350 +/- 20.5 pmol/mg cell protein. The binding affinities of the various analogues were correlated with their ability to stimulate intracellular cyclic AMP synthesis (Lys8-vasopressin less than deamino(8-D-Arg)-vasopressin less than oxytocin). PMID- 6267103 TI - Nature of the immunoreactive neurophysins in ectopic vasopressin-producing oat cell carcinomas of the lung. Demonstration of a putative common precursor to vasopressin and neurophysin. AB - In an attempt to delineate the nature of the immunoreactive neurophysins in oat cell carcinomas of the lung with ectopic vasopressin production, tumor neurophysins were characterized by gel filtration and by electrophoresis. In all of the five tumor tissues, activities of both vasopressin and nicotine-stimulated neurophysin (NSN) determined by radioimmunoassay were demonstrated. A small amount of oxytocin as well as estrogen-stimulated neurophysin was detected in three of the tissues. When tissue extract was subjected to Sephadex G-50 gel filtration in 0.2 N acetic acid, the major portion of immunoreactive NSN emerged in the fractions corresponding to the molecular size of 10,000. The migration pattern of NSN in these fractions on electrophoresis was qualitatively the same as that of NSN extracted from human posterior pituitary glands. In addition to this major neurophysin, immunoreactive NSN with the molecular size of 20,000 was consistently demonstrated in three tumor extracts. This high molecular weight form of neurophysin represented 6.5--8.7% of total NSN immunoactivities in each tumor extract and its elution profile was not changed when analyzed under denaturating conditions in 6 M guanidine hydrochloride. On electrophoresis, it migrated near the gamma globulin region; however, the peak was broad suggesting that it consists of more than two different molecular populations. A substantial portion of the high molecular weight NSN appears to be a glycoprotein judging from its binding to concanavalin A. When the high molecular weight from of neurophysin was incubated with trypsin, essentially all of the activities were converted into NSN with the molecular size of 10,000. Moreover, an equimolar amount of vasopressin was liberated after the treatment, the elution pattern of which closely resembled that of synthetic arginine vasopressin. When a lower concentration of trypsin was used, some of the 20,000-dalton neurophysin exhibited activities of both NSN and vasopressin. Since the antivasopressin serum used in this study appeared to be directed toward the ring portion side of vasopressin, these results suggest that this 20,000-dalton neurophysin is, in all probability, a common precursor to vasopressin and neurophysin, and that vasopressin may be located in the middle of the precursor molecule. PMID- 6267104 TI - Glucocorticoid-induced alterations in the sodium potassium pump of the human erythrocyte. AB - To evaluate the effects of glucocorticoids on the Na-K pump in human subjects, were evaluated the intracellular sodium and potassium, 42K influx across and the [3H]ouabain binding to cell membranes of intact human erythrocytes from a group of subjects taking glucocorticoids and a group of normal subjects. Intracellular sodium concentration was lower (7.2 +/- 0.4 vs. 10.9 +/- 0.2 mmol/liter cell water) and intracellular potassium concentration higher (149.8 +/- 1.5 vs. 137.2 +/- 1.2 mmol/liter cell water) in erythrocytes from steroid-treated patients. In spite of a significantly decrease intracellular sodium which normally diminishes ouabain-sensitive 42K influx, the ouabain-sensitive K influx was unchanged in erythrocytes from the steroid-treated group. Maximum [3H]ouabain binding was markedly higher in the steroid-treated group (835 +/- 44 vs. 449 +/- 11 sites/cell). There was close linear correlation between [3H]ouabain binding and inhibition of K pump, suggesting the specificity of ouabain binding to Na-K pump sites on the cell membrane. Association kinetics for ouabain were similar in the two groups despite the marked difference in the amount of [3H]ouabain binding. External potassium concentration required for half-maximum ouabain-sensitive K influx was identical in the two groups. Thus, the additional Na-K pump sites in the steroid-treated group were qualitatively similar to those in normals. These results suggest that administration of glucocorticoids leads to an increase in the number of Na-K pump sites. The increase in the number of Na-K pump sites may explain the low levels of intracellular sodium and higher cell potassium observed in steroid-treated subjects. PMID- 6267105 TI - Hormonal stimulation of eucaryotic cell ADP-ribosylation. AB - The effect of thyrotropin (TSH) on the ADP-ribosylation of endogenous thyroid cell acceptor proteins was examined. Cells were "permeabilized" at 4 degrees C in hypotonic medium and then exposed to [(32)P]- or [(3)H-adenine]NAD(+). The net incorporation of labeled ADP-ribose was measured by trichloroacetic acid precipitation. TSH (100 mU/ml) enhanced ADP-ribosylation with a maximum effect after 30-60 min in the majority of experiments. TSH stimulation was observed even when the incubation contained 1,000-fold more exogenous NAD(+) than the amount of NAD(+) contributed by the permeabilized cells, indicating an effect on enzymatic activity rather than an alteration in NAD(+) pool size or specific activity. No incorporation of radioactivity from labeled NAD(+) was observed in cells not rendered permeable to NAD(+) by hypotonic shock. TSH did not increase the rate of disappearance of trichloroacetic-precipitable radioactivity and did not contain intrinsic NAD(+) glycohydrolase activity. Alkali and snake venom phosphodiesterase, but not ribonuclease or deoxyribonuclease digestion of trichloroacetic acid precipitable thyroid cell radioactivity, revealed primarily 5'-AMP, consistent with an effect of TSH on mono-ADP ribosylation. Nicotinamide and thymidine (50 mM) inhibited both basal and TSH-stimulated ADP-ribosylation of thyroid cell protein. Dibutyryl cyclic (c)AMP (0.1 mM) inhibited endogenous ADP ribosylation by approximately 35% but had no effect at lower concentrations. 0.5 mM isobutylmethylxanthine inhibited this reaction by approximately 60%. We suggest that TSH enhances thyroid cell ADP-ribosylation by a mechanism independent of cAMP as a second messenger, and that ADP-ribosylation plays a role in the expression of TSH. PMID- 6267106 TI - Influence of peritubular protein on solute absorption in the rabbit proximal tubule. A specific effect on NaCl transport. AB - The effect of removal of peritubular protein on the reabsorption of various solutes and water was examined in isolated rabbit proximal convoluted tubules (PCT) perfused in vitro. In 22 PCT perfused with ultrafiltrate (UF) and bathed in serum, volume absorption (Jv) was 1.44 nl/mm per min and potential difference (PD) was -3.6 mV. When these same PCT were bathed in a protein-free UF, Jv was reduced 38% without a change in PD. Simultaneous measurements of total CO2 net flux (JTCO2) and glucose efflux (JG) showed that less than 2% of the decrease in JV could be accounted for by a reduction in JTCO2 and JG, suggesting that removal of peritubular protein inhibited sodium chloride transport (JNaCl). Therefore, in eight additional PCT, JNaCl was measured, in addition to PD, Jv, JG, and JTCO2. In these PCT, the decrease in total solute transport induced by removal of bath protein was 201.7 +/- 37.5 posmol/mm per min. JG decreased slightly (9.1 +/- 3.9 posmol/mm per min); NaHCO3 transport did not change (9.2 +/- 6.6 posmol/mm per min); but JNaCl decreased markedly (160.6 +/- 35.7 posmol/mm per min). 80% of the decrease in Jv could be accounted for by a decrease in JNaCl. In 13 additional PCT perfused with simple NaCl solutions, a comparable decrease in Jv and JNaCl was observed when peritubular protein was removed without an increase in TCO2 backleak. In summary, removal of peritubular protein reduced Jv and JNacl, but did not significantly alter PD, JG, JTCO2, or TCO2 backleak. The failure to inhibit JG and JTCO2, known sodium-coupled transport processes, indicates that protein removal does not primarily affect the Na-K ATPase pump system. Furthermore, since PD and TCO2 backleak were not influenced, it is unlikely that protein removal increased the permeability of the paracellular pathway. We conclude that protein removal specifically inhibits active transcellular or passive paracellular NaCl transport. PMID- 6267107 TI - Inhibition of human polymorphonuclear leukocyte function by 2-cyclohexene-1-one. A role for glutathione in cell activation. AB - 2-cyclohexene-1-one and diethyl maleate specifically decrease reduced glutathione (GSH) levels in human polymorphonuclear leukocytes (PMN) by direct conjugation, and by interaction with the glutathione-s-transferase system. Using these two nontoxic reagents we have examined the effect of decreased GSH levels on five parameters of PMN activation: superoxide generation, release of the lysosomal enzymes lysozyme and beta-glucuronidase, and increases in the influx of Na+ and Ca2+. When PMN pretreated with 2-cyclohexene-1-one or diethyl maleate were incubated with formyl-methionyl-leucyl-phenylalanine (FMLP) or the proteolytic fragment of the fifth component membrane of complement, C5a, agents that interact with surface membrane receptors, increases in all five parameters were inhibited in a dose-dependent manner. For O-2 generation and lysosomal enzyme release the ID50 for 2-CHX-1 was 40--90 micrometers corresponding with a 30--50% decrease in intracellular GHS. In contrast stimulation of treated PMN by the divalent cation ionophore A23187 or 5-hydroxyeicosatetraenoic acid was much less sensitive to depressed GSH; the ID50 for 2-cyclohexene-1-one was 1 mM or greater, corresponding with an 80--90% decrease in GSH. The effect of lowered GSH was not the result of decreased binding of FMLP to surface receptors because [3H]-FMLP binding studies demonstrated a two- to three-fold increase in the number of available binding sites. These data indicate that normal GSH levels are necessary for the transduction of the activation signal from the exterior to the interior of the PMN, but once initiated the activation sequence proceeds normally despite markedly lowered intracellular GSH. PMID- 6267108 TI - Diagnostic accuracy of cytology and biopsy in primary bronchial carcinoma. AB - The accuracy of diagnosis in 656 patients with the four common histopathological types of primary lung cancer has been assessed by comparing the cell type diagnosis made on cytological and histological investigation with that determined by examination of the surgically resected or necroscopy specimen. The accuracy of diagnosis achieved by cytological examination of sputum and bronchial aspirate, and by bronchial biopsy histology was over 85%. The least accurate diagnostic procedure was percutaneous needle biopsy (62%). Squamous and small cell tumours were accurately diagnosed by all four investigations but errors were made in the diagnosis of large cell and adenocarcinomas. Nearly half the number of patients (43%) with large cell carcinoma were later reclassified as having squamous carcinoma and of the patients with adenocarcinoma 32% had been predicted to be squamous and 18% large cell carcinoma. We consider such quality control of pretreatment diagnosis mandatory in management of individual patients and before enrollment in clinical trials. PMID- 6267109 TI - The distal limb motor neurons in the thoracic ganglion of the spiny lobster. AB - The 16 motor neurons which innervate the muscles in the limb distal to the autotomy plane have been found in the third thoracic ganglion of the southern rock lobster, Jasus novaehollandiae. They were traced from the autotomy plane to the ganglion by stripping them from the small and large leg nerves to the edge of the ganglion where they were filled with cobalt dye. Cell bodies of 11 of these neurons lie in an anterior cluster of somata, and the remainder lie in a ventral rind of somata. The neurites from these somata expand into enlarged central segments, 400 micrometers long and 10-30 micrometers in diameter. These segments run parallel and in apposition to each other as they course through the neuropile a few cell layers beneath the dorsal surface of the ganglion. Near their origin some central segments send branches both medially between fibers of the interganglionic connectives, and anteroventrally into the connective. Distally the segments give rise to side branches which project around the anterior and posterolateral borders of the neuropile. The central segments constrict near the lateral edge of the neuropile, rise to its surface, and form axons. Eight axons, including those which innervate the flexor muscle of the carpus, enter an anterior motor tract which exists the side of the ganglion in a first root, the source of the small leg nerve. The remaining eight axons, which include those that innervate the extensor muscle of the carpus, enter a posterior motor tract which exists the side of the ganglion in a second root, the source of the large leg nerve. All the motor fibers which innervate the muscles of the limb, with the exception of the retractor of the coxa, run in these two tracts within the ganglion. Fibers which innervate the retractor of the coxa and the muscles of the thorax leave the ganglion in a third root at the posterodorsal border of the ganglion. The central segment, as the common structure of confluence of neuropilar branches, is the likely candidate for the integrating region of each neuron. PMID- 6267110 TI - Granular cell tumor. An analysis of 16 cases and review of the literature. AB - Sixteen patients with granular cell tumors were seen between 1964 and 1979. The medical data of these patients showed an average age incidence of 39 years and a greater frequency among Negroes (69%) and in female patients (62.5%). The most common sign (in 12 of 16 patients) was the presence of an asymptomatic mass. There was a total of 88 tumors in 16 patients; 74 arose in the skin, 6 in the oral cavity, 2 each in the breast and perineum, and 1 each in the larynx, parotid gland, eyelid, and appendix. Multiple tumors were noted in 4 patients (25%), all of whom were Negroes. The histogenesis of this tumor is still controversial but appears to favor the theory of multipotential undifferentiated mesenchymal cell origin. PMID- 6267111 TI - Computed tomography of the pulmonary hila: 2. abnormal anatomy. AB - Computed tomography can be used to evaluate abnormal pulmonary hila. A series of cases is presented that illustrate the appearance of dilated pulmonary arteries, absent pulmonary artery, hilar adenopathy, and hilar masses. PMID- 6267112 TI - Computed tomography of virally induced canine brain tumors: a preliminary report. AB - Seven neonatal dogs were inoculated intracerebrally with Avian Sarcoma Virus (ASV) and studied by computed tomography (CT) for intracranial tumors. The tumor yield was five anaplastic astrocytomas and two sarcomas, with an average latency of 57 days. Computed tomography accurately detected all tumors over 5 mm in diameter and predicted the size of the tumors within 3 mm. The intensity of contrast enhancement was directly related to the dose of Conray-60. The area of enhancement on the CT scan correlated precisely with tumor permeability as determined histologically with horseradish peroxidase (HRP). Edema seen in CT scans correlated well with edema present in histological sections. Peritumoral edema was impermeable to both Conray-60 and HRP. The ASV-induced canine brain tumor model appears well suited for future CT studies. PMID- 6267113 TI - The effects of db-cAMP and related compounds on the outgrowing epidermis in vitro. PMID- 6267114 TI - Skin testing for penicillin allergy. PMID- 6267115 TI - Skin testing to detect penicillin allergy. AB - Skin testing for penicillin allergy with penicillin G (Pen G), penicilloic acid (PA), and penicilloyl poly-L-lysine (PPL) was performed on 740 subjects, and the results were assessed from epidemiologic and immunologic perspectives. Approximately 95% of these patients had histories of apparent allergic reactions to beta-lactam antibiotics, and 63% were skin-test positive. The prevalence of positive skin tests was related to the time that had elapsed between clinical reactions and skin testing. Ninety-three percent were skin-test positive 7 to 12 mo after reactions, and 22% were positive 10 yr or more after reactions. Patients under 30 yr of age had a prevalence of positive skin tests 1.7-fold higher than older patients. Testing with PPL, PA, and Pen G detected 76.3%, 55.3%, and 57.1% of the positive patients, respectively. Omission of PPL, PA, or Pen G would have led to a failure to detect 25.6%, 7.2%, and 6.2% of the positive patients, respectively. Subjects with skin tests positive to penicillin often reacted to skin tests with other beta-lactam antibiotics; 73% (41 of 56) reacted to ampicillin and 51% (38 of 74) reacted to cephalothin. No serious allergic reactions were provoked by testing. None of the 83 skin test--negative patients treated with beta-lactam antibiotics immediately after testing experienced acute allergic reactions. Two patients developed mild urticaria beginning 3 and 5 days into therapy. One skin test--negative patient experienced urticaria 3 hr after receiving oral penicillin 6 mo after skin testing. This patient's skin-test status immediately before therapy was unknown. These results support the position that testing with PPL, PA, and Pen G is a rapid, safe, and effective method for identifying patients at risk, or not at risk, for allergic reactions to penicillin. PMID- 6267116 TI - The biologic activity of mast cell granules in rat skin: effects of adrenocorticosteroids on late-phase inflammatory responses induced by mast cell granules. PMID- 6267117 TI - Somatosplanchnic reflex discharges in rats. AB - Splanchnic efferent reflex discharges caused by electrical stimulation of limb afferent nerves or intercostal afferent nerves were studied in chloralose urethane anesthetized rats. Stimulation of the limb afferent nerve produced late supraspinal reflex discharges via group II and III afferent excitation. Stimulation of the intercostal afferent nerve produced early spinal reflex discharges via group II and III afferent excitation and also late spinal reflex discharges via group IV afferent excitation. Intercostal afferent nerve stimulation seemed to strongly depress the splanchnic late supraspinal reflex discharges. PMID- 6267118 TI - Release of [14C]quinacrine from peripheral and central nerves. AB - Incubations of intestinal mouse smooth muscle sheets including Auerbach's plexus and slices of the spinal cord in buffer containing low concentrations of labelled quinacrine ([14C]QC) result in a high affinity binding of QC to certain nerve fibres. Various means of depolarization, such as veratridine, high potassium and electrical field stimulation, were used to assess quantitatively the release of QC from nerves. Under optimal release conditions, all 3 types of depolarizations induced a clearcut increase in radioactivity of a continuously superfused buffer. When intestinal muscle sheets were incubated in high concentrations of QC (5 . 10(-6)--5 . 10(-5) M) the depolarization-induced release was blocked. Similarly, high concentrations of QC (10(-5) M) blocked release of [3H]noradrenaline from adrenergic nerves. Low QC concentrations did not affect the depolarization induced release of [3H]noradrenaline from adrenergic nerves but caused a moderately increased spontaneous overflow of noradrenaline. The present data, together with previous studies, permit the conclusion that QC in low concentrations can be used to label selectively a population of non-adrenergic nerve fibres. This binding is closely related to the transmitter storage and release mechanisms and can be used to study the activity of such nerves. PMID- 6267119 TI - Endorphin-parasympathetic interactions in spinal shock. AB - We have recently shown that the opiate antagonist naloxone can partially reverse the hypotension which accompanies spinal cord transection, through actions on opiate receptors in the central nervous system. In the present studies we demonstrate that either vagotomy or atropine prevents the ability of naloxone to reduce the hypotension caused by spinal transection in the rat and cat. Since the peripherally acting methyl-atropine blocks the cardiovascular effects of centrally administered naloxone in this model, these findings imply an interaction between endorphin systems and central parasympathetic centers in spinal shock. This interaction results in a depression of cardiovascular function which is mediated through cholinergic vagal efferent pathways. Furthermore, the fact that naloxone reduces the hypotension following spinal transection, along with the role of the parasympathetic system in this process, appears to question the classic conception that such hypotension results entirely from interruption of descending sympathetic pressor pathways. Finally, the beneficial cardiovascular effects of naloxone in spinal shock may have important therapeutic implications in the management of spinal cord injury. PMID- 6267120 TI - Neuronal electrical activity in the submucosal plexus of the cat small intestine. AB - Extracellular recording of action potential discharge from single units in the submucosal plexus of cat small intestine revealed both continuously active and electrically silent neurons. The continuously active neurons consisted of slow and fast burst-type units and single-spike units. The silent neurons were activated by input transmitted from adjacent ganglia by the interganglionic fiber tracts and discharged in response to mechanical deformation of the ganglia and to electrical stimulation of adjacent ganglia. Both excitatory and inhibitory interneuronal interactions were observed between ganglion cells with burst-type discharge patterns and the electrical activity of some of these cells was influenced by electrical stimulation of adjacent ganglia. The observations are consistent with the concept that the individual ganglia of the submucosal plexus are interconnected into a single integrative network. PMID- 6267121 TI - An unusual variation of a malignant fibrous histiocytoma: a case report. AB - This case study was written to acquaint the reader with the etiology, incidence, pathology, clinical course, and treatment of a variation of the malignant fibrous histiocytoma. In review of the literature, only three cases of malignant fibrous histiocytoma (myxoid variant) were found in the foot. The authors want to impress on the reader the necessity of the pathologic study of any lesion in the foot regardless of its gross appearance. PMID- 6267122 TI - The prolongation of life: a comparison of antioxidants and geroprotectors versus superoxide in human mitochondria. AB - Metabolically-active human mitochondria were impregnated with a site-specific, chemiluminescent probe and different mixtures of known or suspected antioxidants and/or geroprotectors. Superoxide flux from the endomitochondrial respiratory chain and from exomitochondrial sources were measured in regard to the degree of protection from different geroprotective mixtures. In human mitochondria, mixtures of choline, RNA, ACF 223, BHT, copper, alpha-tocopherol, ascorbic acid and mercaptans showed some indication of superoxide scavenger effect, especially when compared to hydroxy-group substances such as mannitol, glucose and ethanol. Both in rat and human mitochondria, strong synergetic effects were evidenced by formulations incorporating alpha-tocopherol, BHT, ACF 223 and mercaptoamino acids. PMID- 6267123 TI - [A case of cylindroma of the cervix (author's transl)]. AB - The authors, in this article, report on a case of the relatively rare condition of cylindroma of the cervix (adenoid cystic carcinoma). The typical features as seen under the optical and electron microscope are broadly as well as the different techniques available to treat this rare lesion, which is more fulminating in its evolution than the similar condition when it occurs in the skin or the breast. PMID- 6267124 TI - Pulmonary maturation in the hypophysectomised ovine fetus. Differential responses to adrenocorticotrophin and cortisol. AB - Pulmonary maturation in six ovine fetuses hypophysectomised by a cryosurgical method at 0.7-0.8 of pregnancy and delivered by hysterotomy at 152.2 +/- 2.9 (SD) days was compared with that in seven control fetuses delivered at 144.5 +/- 3.5 days. Both the wet and the dry weight of the lungs was less in the hypophysectomised fetuses but total DNA did not differ. Lung volumes at 40 cm of H2O and at 5 cm of H2O on deflation in hypophysectomised fetuses were less than one-third that of controls. Saturated phosphatidylcholine, as an estimate of surfactant, was lower in both lung tissue and lavage fluid. A further group of hypophysectomised fetuses was infused intravenously either with cortisol at 1 mg/h for 72 h (n = 6), or with ACTH1-24 at 5 microgram/h for 84 h (n = 6) before delivery at 155.0 +/- 2.1 days and 154.2 +/- 3.9 days respectively. None of the indices of pulmonary maturation in the cortisol-treated fetuses differed from those in untreated hypophysectomised fetuses whereas values for lung volumes at 40 and 5 cm of H2O in ACTH-treated fetuses were more than twice those of untreated hypophysectomised fetuses and did not differ significantly from controls. In addition, the amount of saturated phosphatidylcholine in lavage fluid was greater in ACTH-treated fetuses (0.13 +/- 0.10 mg/g) than in untreated hypophysectomised fetuses (0.04 +/- 0.48 mg/g). Lung volume at 40 cm of H2O in four fetuses that were thyroidectomised at the time of hypophysectomy responded to ACTH as in hypophysectomised fetuses with intact thyroids but other indices were unaffected. We conclude that hypophysectomy retards pulmonary maturation in fetal sheep. Since ACTH restores distensibility and increases alveolar surfactant in the absence of other pituitary hormones it is likely that ACTH has a major role in lung maturation. The lack of response to cortisol suggests that the effect of ACTH is not mediated only by circulating cortisol. PMID- 6267125 TI - The mechanisms which affect the periodic cycle of Pacific Wuchereria bancrofti microfilariae. AB - 1. Investigations were made of the effect of various procedures in raising or lowering the microfilaria count of Pacific type Wuchereria bancrofti in the peripheral blood. 2. Raising the body temperature in the early morning was followed by a moderate fall in the counts. Breathing increased oxygen, or reduced oxygen (hypoxia) or increased carbon dioxide, or the ingestion of sodium bicarbonate produced no consistent and significant change in the count. Ingestion of glucose (in one volunteer) was followed by a small rise in the count. Muscular exercise was followed by a fall in the count, which is interpreted as probably being a response to a lower concentration of oxygen in the venous blood returning to the lung. 3. It has not been possible to identify the physiological components on the circadian rhythm of the human body which entrain the cycle of these microfilariae. Attempts to obtain evidence incriminating the stimuli described above have been unsuccessful. PMID- 6267126 TI - Immunocytochemical localization of receptor human chorionic gonadotropin complexes in rat leydig cells. AB - Localization of receptor-bound human chorionic gonadotropin (hCG) in rat testis was studied by the peroxidase-antiperoxidase (PAP) complex method. The rats were injected with a single intravenous dose (1000 IU) of hCG. Three, 6, 12, and 24 hr after injection the testes were removed for localization of the hormone. The hormone localized to the periphery of the Leydig cells at all observation points. The intensity of the staining varied between the cells, suggesting that the number of receptors or the accessibility of the receptors to the circulating hormone varies from one cell to another. The staining surrounded the Leydig cells unevenly, but no progressive patching or capping was found. This observation suggests that hCG binds preferentially to the cell surface areas directed toward the capillaries. Compatible results were obtained with anti-hCG serum and with antisera against the hCG subunits. These results are consistent with previous observations that the luteinizing hormone (hCG) receptors accessible to the circulating hormone are located at the surface of the Leydig cells. PMID- 6267127 TI - Correlated biochemical and cytochemical studies of nicotinamide adenine dinucleotide phosphatase (NADPase) activity in ameloblasts using structural analogues of NADP. AB - The effects of altering the molecular structure of nicotinamide adenine dinucleotide phosphate (NADP) on enzymatic hydrolysis of the monoester phosphate group was examined at pH 5.0 in rat incisor ameloblasts using eight analogues of the oxidized form of the beta-isomer of NADP (beta-NADP+) modified in either the nicotinamide or adenine regions, or at the site for attachment of the monoester phosphate group to the molecule. Biochemical studies with whole homogenates of unfixed enamel organs revealed that the Michaelis-Menten constant (KM) and the maximum rate of dephosphorylation (Vmax) were different for these analogues relative to values estimated with beta-NADP+ as substrate. For example, the KM value was 3-fold higher and the Vmax value was lower by about 1/2 with the reduced form of the molecule as substrate. The KM value was about 2-fold higher but the Vmax value was about the same with an analogue lacking the nicotinamide group as substrate, while both the KM and the Vmax values were about 2-fold higher with an analogue containing an ethylene group covalently linked to adenine as substrate. In contrast, the KM value was markedly reduced (1/15) and the Vmax value was elevated (4-fold) using an analogue as substrate which contained the phosphate group attached at the 3'-position (3'-NADP+), rather than the 2' position as in beta-NADP+ and other analogues. Cytochemical studies with glutaraldehyde-fixed enamel organs revealed that reaction product from hydrolysis of beta-NADP+ and other analogues containing the phosphate group attached at the natural 2'-position was localized within the intermediate saccules of the ameloblast Golgi apparatus. Reaction product from hydrolysis of 3'-NADP+, however, was localized at a different site, that is, within granules and membranous connections of the GERL system in the cell. Hence, 3'-NADP+ was not hydrolyzed by NADPase but by another enzyme tentatively identified as Coenzyme A phosphatase. PMID- 6267129 TI - Induction of complement receptor expression cell lines derived from human undifferentiated lymphomas. I. Mode of action of theophylline and inhibition by certain purines. PMID- 6267128 TI - The oxidative metabolism of thioglycollate-elicited mouse peritoneal macrophages: the relationship between oxygen, superoxide and hydrogen peroxide and the effect of monolayer formation. AB - The oxygen and glucose metabolism of peritoneal macrophages harvested from untreated mice (resident cells) and mice given an i.p. injection of thioglycollate broth (thioglycollate cells) were examined. Thioglycollate cells consumed approximately 3 times as much O2 at rest and during phagocytosis as resident cells, but oxygen reduction products (superoxide and hydrogen peroxide) could be recovered in only minimal amounts despite triggering by phagocytosis or exposure to PMA. Indirect evidence for the formation of oxygen reduction products such as O2- by thioglycollate cells was obtained by observation of the major pathways for glucose oxidation and NBT dye reduction. When thioglycollate cells were allowed to adhere to a glass surface O2- and H2O2 were easily recovered in the extracellular medium with a 20-fold increase above cells in suspension exposed to PMA. This study suggests that thioglycollate-elicited macrophages have a vigorous oxidative metabolism but that recovery, and perhaps utilization, of O2 reduction products formed will depend on the conditions of incubation. These events may be significant both for the study of parameters of macrophage "activation" in vitro as well as the function of these cells in vivo. PMID- 6267130 TI - Induction of complement receptor expression in cell lines derived from human undifferentiated lymphomas. II. Characterization of the induced complement receptors and demonstration of the simultaneous induction of EBV receptor. AB - We have studied the specificity of complement receptors induced by theophylline in 2 cell lines derived from undifferentiated lymphomas, one of Burkitt's type, and compared it to that of complement receptors in other cell types. Both C3b and C3d receptors were induced. The induced C3b receptor differed from the C3b receptor of mature normal lymphocytes, polymorphonuclear leukocytes and the cells of a nodular lymphoma in 2 respects. Firstly, it bound C3b much less avidly (by a factor of several hundred-fold) and secondly, we were unable to demonstrate C4b binding. EBV receptors were induced at the same time as complement receptors, and permitted the conversion of a greater fraction of cells to EBNA positivity after experimental infection with EBV. The induction of receptors was not associated with a change in the fluidity of the plasma membranes and our data do not favor a different orientation of induced receptors within the membrane as compared to receptors of other cell types--a potential explanation for the different specificities. Our findings are consistent with the possibility that the complement receptors of lymphocyte precursors differ from these of mature lymphocytes. PMID- 6267131 TI - Regulation by PGE2 of the production of oxygen intermediates by LPS-activated macrophages. AB - The regulation by prostaglandin E2 (PGE2) of production of oxygen radicals by bacterial lipopolysaccharide-(LPS) activated macrophages was studied in vitro. A 48-hr incubation of murine thioglycollate-elicited macrophages with LPS (0.1 micrograms/ml) resulted in an enhanced ability of these cells to produce oxygen radicals when challenged with phorbol myristate acetate (PMA). Macrophages incubated for 48 hr without LPS did not produce measurable amounts of oxygen radicals when exposed to this triggering stimulus. Thus, PMA-triggered production of oxygen radicals was the result of macrophage activation by LPS. The PMA triggered production of oxygen radicals by the LPS-activated macrophages was inhibited when PGE2 (10(-5) to 10(-9) M) was present during the incubation with LPS. Inhibition by PGE2 occurred during the early stages of macrophage activation, since the addition of PGE2 24 hr after LPS no longer inhibited the production of oxygen radicals by the macrophages. This inhibitory effect of PGE2 on the LPS-induced activation of macrophages could be reproduced by cyclic adenosine-monophosphate (cAMP) agonists, such as isoproterenol and cholera toxin as well as by the cAMP analog dibutyryl-cAMP, suggesting a cAMP-mediated mechanism for the inhibitory effect of PGE2 on macrophage activation by LPS. Previous reports have implicated prostaglandins as mediators of destructive processes associated with chronic inflammation. Our findings suggest that PGE2 may, on the other hand, reduce tissue damage in a chronic inflammatory site by inhibiting the production of oxygen radicals by macrophages activated in the sera. PMID- 6267132 TI - How complement kills E. coli. I. Location of the lethal lesion. AB - We have studied the action of human complement (C) on E. coli membranes. We find, as have others, that C disrupts the outer membrane (OM), allowing the release of periplasmic proteins. In addition, we have found 1) that in the complete absence of lysozyme, C damages the inner membrane (IM), 2) IM damage is different from OM damage in that only small molecules traverse a damaged IM whereas macromolecules traverse damaged OM, 3) IM damage and OM damage occur with identical kinetics and dose response, suggesting that IM and OM damage are closely coupled events, and 4) upon the addition of purified C8 and C9 to the washed cellular intermediate, E. coli C 1-7, both IM and OM are damaged coordinately. These results, taken together, suggest that C damages E. coli membranes by acting at a site contiguous with both membranes. We speculate that C may simultaneously gain access to both membranes by acting at the junctions between IM and OM. PMID- 6267133 TI - Activation of human neutrophils with 1-O-hexadecyl/octadecyl-2-acetyl-sn-glycerol 3-phosphorylcholine (platelet activating factor). AB - 1-O-Hexadecyl/octadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine (AGEPC), the acetylated alkyl phosphoglyceride known as platelet-activating factor, stimulated human neutrophil (PMN) exocytosis, migration, superoxide production and aggregation over a concentration range of 10(-10) to 10(-5) M. AGEPC-induced PMN exocytosis of azurophilic (myeloperoxidase and beta-glucuronidase) and specific (lactoferrin and lysozyme) lysosomal granules was rapid (T 1/2 = 20 sec), dependent on the presence of cytochalasin B, but was not associated with release of cytoplasmic LDH. As seen with the complement-derived peptide stimulus, C5a, AGEPC-initiated PMN enzyme release was dependent on temperature and cellular glycolysis but not on the presence of extracellular Ca++. When analyzed by gradient analysis, PMN migration caused by AGEPC was primarily chemotactic in nature. An unusual feature for both enzyme secretion and migration was a decrease in response between 10(-6) M and 10(-5) M AGEPC. This decreased responsiveness could be explained by rapid PMN desensitization occurring at high AGEPC concentrations, limiting the overall cellular response. Rapid desensitization for exocytosis was demonstrated in PMN stimulated with AGEPC in the absence of cytochalasin B. When cytochalasin B was added subsequently and PMN challenged with AGEPC or C5a, stimulus-specific desensitization to AGEPC but not C5a-induced lysosomal enzyme release occurred. PMN desensitized to C5a responded normally to a subsequent AGEPC challenge. Stimulation of all the PMN functions examined was markedly attenuated with removal of the 2-acetyl group from AGEPC (lyso GEPC). These results suggest that AGEPC stimulates a wide variety of human PMN responses by a receptor-like mechanism, dependent on the short chain fatty acid ester in the 2-position of the alkyl phosphoglyceride. PMID- 6267135 TI - Separation of tumor-seeking small lymphocytes and tumor cells using Percoll velocity gradients. AB - Using the polyoma virus-induced ascitic SEYF-a tumor, we evaluated isopycnic and velocity sedimentation gradients of Percoll as methods for separating tumor seeking lymphocytes and tumor cells. It was established that the velocity sedimentation method is suitable for separation of small lymphocytes lodging within the SEYF-a tumor. This was confirmed by a serological analysis of the separated SEYF-a cell population. The results of this study strongly support our previously reported data demonstrating the in vivo coating of the tumor cells proper with potentially cytotoxic antibodies. PMID- 6267134 TI - Metastatic tumor cell variants with increased resistance to infection by Semliki Forest virus. AB - Semliki Forest virus (SFV) is an interesting virus for cell interaction studies because it binds directly to the cells' major histocompatibility antigens. We used this reagent to study the expression and functional properties of H-2 molecules on murine tumor lines that are closely related but differ greatly in metastatic capacity. Tumor cell variants with high metastatic capacity showed an increased resistance to virus infection, an effect that was selective for SFV. Although the high metastatic tumor lines did not express less H-2 antigens than the low metastatic ones, they bound much less of the SFV viral glycoproteins. PMID- 6267136 TI - Rapid solid-phase enzyme immunoassay for antibodies to viruses and other microbes: effects of polyethylene glycol. AB - A rapid and sensitive solid-phase enzyme immunoassay (EIA) was developed for determination of serum antibodies, including addition of 4% (w/v) polyethylene glycol (PEG) to the diluent buffers. This modification accelerated the antigen antibody reactions and made it possible to complete the assay within 2 h and to incubate at room temperature only. The enhancing effect of the polymer was particularly prominent in the second solid-phase immune reaction, the interaction between the antigen-bound antibody and the enzyme-labeled anti-immunoglobulin. The PEG-EIA procedure was successfully applied in the assay of antibodies to rubella, influenza A, herpes simplex and cytomegalo viruses, to Mycoplasma pneumoniae and Toxoplasma gondii. PMID- 6267137 TI - Three-step isolation of human blood monocytes using discontinuous density gradients of Percoll. AB - A three step method for the purification of normal human blood monocytes is described. The procedure consists of a combination of dextran sedimentation, Ficoll-Isopaque (F-I) centrifugation and isopycnic centrifugation on discontinuous gradients of Percoll. No selective loss of monocytes was observed after the first step, and after F-I centrifugation mononuclear cells (MNC) were obtained, of which 20 +/- 6% were monocytes. The MNC were further separated on hyper-osmotic and iso-osmotic discontinuous density gradients of Percoll. The best purification of monocytes occurred on hyper-osmotic density gradients and the density interface between 1.074 and 1.066 g/ml yielded 85 +/- 7% monocytes, 13 +/- 7% lymphocytes and 1 +/- 1% granulocytes. 77 +/- 16% of the monocytes obtained after F-I centrifugation, were recovered in this interface. The purified monocytes were viable and retained their capacity to mature into macrophages. The whole procedure takes about 5 h, is reproducible and can be applied to small and large volumes (500 ml) of blood. PMID- 6267138 TI - Staphylococcal protein A-enzyme immunoglobulin conjugates: versatile tools for enzyme immunoassays. AB - This report describes the use of peroxidase-labeled staphylococcal protein A to prepare conjugates suitable for direct enzyme immunoassays (EIAs). Such conjugates were used to develop direct EIA systems for the measurement of two antigens associated with human infections, human rotavirus and Haemophilus influenzae type b polysaccharide. Both systems were as sensitive or more sensitive than currently available EIAs for the measurement of standard antigens. In addition, both systems could be utilized to correctly identify the antigens in clinical specimens obtained from sick patients. Efficient enzyme conjugates prepared with enzyme-labeled staphylococcal protein A were simple to formulate providing that immunoglobulin of the appropriate animal species was available as the source of antibody. The use of such conjugates might increase the availability of practical EIA systems for the measurement of a wide range of medically important antigens. PMID- 6267139 TI - MHC gene control of growth of avian sarcoma virus-induced tumours in chickens: a study on the role of virus strains. AB - A comparison was made of growth patterns (progression/regression) of tumours induced by different strains of avian sarcoma virus in two partially congenic inbred lines of chickens homozygous for different MHC haplotypes. In each instance studied, the ability to regress tumours was shown to be a dominant trait controlled by MHC-linked genes. The results also demonstrate a difference in growth pattern between tumours induced by different strains of virus in an inbred line as well as different growth patterns of tumours induced by the same strain of virus in the two inbred lines. We conclude that the MNC-linked resistance gene is part of a polymorphic genetic region and, in addition, that there is immunogenic heterogeneity of the viral gene product expressed on tumour cells induced by closely related viral strains which is relevant to tumour regression. We suggest that the product of the src gene, p60src, is a plausible candidate for the immunogenic target of the MHC-linked rejection response. PMID- 6267140 TI - Complementing MHC- and non-MHC-linked genes and resistance to avian sarcoma virus induced tumours in inbred lines of chickens. AB - Schmidt-Ruppin Rous sarcoma virus, subgroup B (SR-RSV-B), was inoculated into the wingwebs of chickens from three partially congenic inbred lines, G-B1, G-B2 and G B3, homozygous for different MHC (B region) haplotypes (genotypes = B1/B1, B2/B2 and B3/B3 respectively). All birds developed tumours but only the G-B2 line resisted progressive tumour growth. Birds from lines G-B1 and G-B3 approached 100% susceptibility to progressive tumour growth, whereas most (G-B1 X G-B3) F1 hybrids were resistant to tumours induced by SR-RSV-B. The association of the resistance trait in F1 hybrids with genes of the B region was investigated by testing progeny of (G-B1 X G-B3) X B-B1 F1 and (G-B1 X G-B2) X G-B3 F1 backcross matings. Approximately 27% of the backcross population was resistant to SR-RSV-B induced tumours and these resistant offspring were predominantly of the B1/B3 phenotype. We interpret these results to mean that resistance to progressive tumour growth involves complementation between genes (allelic or at separate loci) linked to or within the B region and that resistance is effective only when the complementing B region genes act in concert with complementing genes which assort independently of the MHC. We suggest that complementing B region-linked genes are homologues of complementing murine H-2-linked Ir genes. The function of the B region in determining growth of sarcomas may therefore be analogous to that of Ir genes. PMID- 6267141 TI - Excision repair of UV-induced pyrimidine dimers in human skin in vivo. AB - The induction and loss of pyrimidine dimers in human skin in vivo was determined using UV endonuclease, alkaline sucrose sedimentations, and the fluorescent detection of nonradiolabeled DNA. The number of dimers induced following exposure of the skin to radiation emitted from a Burdick UV-800 sunlamp was quantitated by reacting the extracted DNA with Micrococcus luteus endonuclease specific for pyrimidine dimers. Exposure to 15 and 30 seconds of radiation emitted from this lamp produced the formation of 12.8 and 23.6 dimers per 10(8) daltons DNA, respectively. Approximately 50% of the dimers induced were lost 58 min after irradiation. Only a small percentage (less than 10) remained 24 hr postirradiation. These data partially characterize the process by which pyrimidine dimers are excised from human skin DNA in vivo. PMID- 6267142 TI - Mechanisms of immunosuppression in cytomegalovirus mononucleosis. II. Virus monocyte interactions. AB - Virus-monocyte interactions were evaluated in patients with mononucleosis due to cytomegalovirus (CMV). Group 1 patients studied about two weeks after the onset of symptoms had lymphocyte responses to concanavalin A (con A) that were maximally suppressed and unaffected by in vitro culture or reconstitution with monocytes. Lymphocytes from group 2 patients studied about three weeks after the onset of symptoms had less markedly suppressed responses, which were reversed by in vitro culture or by reconstitution with monocytes. Monocyte depletion resulted in a marked diminution of fresh lymphocyte responses of group 2 patients but not of group 1 patients. CMV was isolated from blood monocytes of four patients with mononucleosis; intact, infected monocytes were capable of suppressing responses of cultured autologous lymphocytes to con A. Monocytes from uninfected control donors were infected in vitro with CMV and evaluated for the induction of suppressor activity. CMV-infected monocytes were significantly more suppressive for autologous lymphocyte responses to con A than were uninfected monocytes. PMID- 6267144 TI - Selective uptake of [125I]iododeoxycytidine in cells infected with herpes simplex virus type 1. PMID- 6267143 TI - Susceptibility of monkeys to human hepatitis A virus. AB - A stump-tailed monkey, newly caught and without antibody to hepatitis B virus (HAV), was successfully infected with human HAV. The following alterations were observed in the monkey's functions: (1) elevation in activities of serum glutamic pyruvic transaminase, lactate dehydrogenase, and its type 5 isoenzyme (electrophoretically the fastest moving); (2) development of antibody to HAV; and (3) shedding of HAV antigen in feces. The virus isolated from the monkey, designated the Hangzhou A-1A strain of HAV, was serially transmitted to two other stump-tailed monkeys. Thus, the stump-tailed monkey (Macaca speciosa) is susceptible to infection with human HAV. PMID- 6267145 TI - [Methotrexate administration against chorionic tumor in small dose for prolonged time mainly or alleviating the side effect (author's transl)]. PMID- 6267146 TI - A study on multiple bile duct carcinoma. PMID- 6267148 TI - Multiple plasma steroid responses to graded ACTH infusions in patients with primary aldosteronism. AB - We measured the simultaneous responses of eight plasma steroids to the infusion of alpha 1-24 ACTH at incremental rates of 12.5 to 200 mlU/30 min in seven patients with primary aldosteronism (five with adenomas, two with adrenal hyperplasia) and in 10 normal controls studied on regular sodium intakes and while supine. Patients with primary aldosteronism from adenomas had relatively higher concentrations (p less than 0.05) of aldosterone, 18 OH-B, corticosterone, and DOC than the two with hyperplasia and, save corticosterone, above the range of the normal controls. We found inconsistent differences in plasma progesterone, 17-hydroxyprogesterone, deoxycortisol, and cortisol. These findings suggest that the intermediate steps in aldosterone biosynthesis are hypersensitive to physiologic amounts of ACTH in patients with aldosterone-producing adenomas. Plasma levels of steroids distal to progesterone, i.e., DOC, corticosterone, 18 OH-B, and aldosterone, are relatively higher after small amounts of ACTH in patients with adenomas than in normal subjects or those with adrenal hyperplasia. PMID- 6267149 TI - Lymphocyte cAMP concentrations. Elevated lymphocyte cyclic AMP due to release of adenosine during cell preparation. PMID- 6267150 TI - Hidradenoma papilliferum of the external auditory canal. PMID- 6267147 TI - [Evaluation of carcinoembryonic antigen level of serum and tumor tissue in breast cancer patients (author's transl)]. PMID- 6267151 TI - Primary malignant fibrous histiocytoma of bone: a case report. PMID- 6267152 TI - Effect of alpha-melanocyte-stimulating hormone and ovarian steroids on preputial gland function in the female rat. AB - Sexually experienced male rats were used to test the attractiveness of preputial gland odours of female rats. The male rats showed a clear preference for the preputial gland odours of hypophysectomized females given oestradiol benzoate (OB) for 3 or 8 days to those of control rats. Progesterone treatment had no effect on the attractiveness of the preputial gland odours of OB-treated hypophysectomized female rats. Administration of alpha-MSH for either 3 or 8 days, on the other hand, increased the attractiveness to male rats of preputial gland odours of OB-treated hypophysectomized females and the presence of progesterone produced no further change. When administered alone alpha-MSH had no effect on the attractiveness of the preputial gland odours. Other pituitary hormones, such as ACTH and prolactin, had no effect on the attractiveness of preputial gland odours of OB-treated hypophysectomized rats when administered for 3 days. An increase in preputial gland size was only seen when OB, progesterone and alpha-MSH were administered together. It would appear that no relationship exists between the size of the preputial glands and their ability to attract male rats. It is concluded that, while alpha-MSH and progesterone may be important in controlling growth of the preputial glands, an interaction between alpha-MSH and oestrogen is more important for regulating the production of sex attractants by the preputial glands. PMID- 6267153 TI - Protein-bound cyclic AMP and steroidogenesis in the adrenal gland of the rat. AB - Adrenocortical cyclic AMP (both total and protein-bound), and adrenal and plasma concentrations of corticosterone were measured in male rats killed at selected intervals throughout the day. The animals had previously been synchronized for 3 weeks in natural lighting. Adrenal and plasma levels of corticosterone showed similar circadian fluctuations and the onset of their ascending phases started at 13.00 h, maximum concentrations being reached at 21.00 h. On the other hand, a time-lag between the circadian variations of total cyclic AMP and protein-bound cyclic AMP could be seen in adrenocortical tissue. The onset of an increase in adrenocortical protein-bound cyclic AMP was apparent at 15.00 h and the peak occurred at 21.00 h, while total adrenocortical cyclic AMP did not begin to rise before 19.00 h and was maximal at 04.00 h. No direct link between total cyclic AMP and protein-bound cyclic AMP could be seen during the dark phase, suggesting a functional compartmentalization of cyclic AMP in the adrenal gland of the rat. While the ascending phase of the rhythm in steroidogenesis preceded the rise in total adrenocortical cyclic AMP by about 4 h an excellent synchrony between the respective patterns of corticosterone concentration and protein-bound cyclic AMP was noticed. PMID- 6267154 TI - Interaction of alpha-melanocyte-stimulating hormone, melatonin, cyclic AMP and cyclic GMP in the control of melanogenesis in hair follicle melanocytes in vitro. AB - In short-term (48 h) cultures of hair follicles alpha-melanocyte-stimulating hormone (alpha-MSH) and cyclic AMP stimulated melanogenesis through an increase in tyrosinase activity. In contrast cyclic GMP mimicked the effects of melatonin by inhibiting melanin production without causing a concomitant decrease in tyrosinase activity. Both cyclic GMP and melatonin blocked the stimulatory effects of cyclic AMP and alpha-MSH on melanin production but they left the increased levels of tyrosinase activity unaffected. Phosphodiesterase inhibitors (3-isobutyl-1--methylxanthine and papaverine) simultaneously stimulated tyrosinase activity and inhibited melanin production, presumably by allowing endogenous cyclic AMP and cyclic GMP to accumulate intracellularly. It is suggested that whereas MSH stimulates melanogenesis through a cyclic AMP dependent mechanism there must also be an inhibitory cyclic GMP-dependent mechanism, perhaps activated by melatonin, which operates at some post-tyrosinase step in the melanin biosynthetic pathway. PMID- 6267155 TI - Dynamics of the formation and release of corticotrophin releasing activity by the rat hypothalamus in vitro. PMID- 6267156 TI - Secretion of aldosterone in the monotreme mammal, Tachyglossus aculeatus. AB - The secretion of aldosterone and its regulation by ACTH and angiotensin II were investigated in conscious, unrestrained echidnas with chronically implanted jugular catheters. Aldosterone was measured by radioimmunoassay after extraction and isolation by silica gel thin-layer chromatography. The mean concentration of aldosterone in blood plasma of five male and three female echidnas was only 5.4 +/- 1.3 (S.E.M.) pg/ml. During stress (surgery and anaesthesia) the mean concentration increased to 17.6 +/- 3.8 pg/ml. Infusion of beta 1-24 ACTH at a rate of 5 units/kg per h increased the plasma concentration of aldosterone to 53.8 +/- 9.8 pg/ml. Infusion of angiotensin II at rates of 100 and 500 ng/kg per h also increased aldosterone concentration, to 24.1 +/- 8.6 and 35.1 +/- 10.9 pg/ml respectively. Production and metabolic clearance rates were measured by the constant-rate infusion of [3H]aldosterone and found to be 5.0 +/- 2.2 ng/kg per h and 14.3 +/- 1.3 ml/kg per min respectively in the unstimulated state. Production rate was increased approximately sevenfold by the infusion of ACTH at 5 units/kg per h and fourfold and sixfold by infusion of angiotensin II at 100 and 500 ng/kg per h respectively. Metabolic clearance decreased following the infusion of ACTH or angiotensin II. Direct measurement of secretion rate by the collection of adrenal venous blood from three anaesthetized, laparotomized echidnas gave values of 9.4, 15.6 and 8.8 mg/kg per h. It is concluded that the adrenal secretion of aldosterone in the echidna is extremely low compared with that in other mammals but the response to stress, ACTH and angiotensin II indicates the presence of typical mammalian control mechanisms for its secretion. PMID- 6267158 TI - [An enzymic method for the determination of cefotaxim in serum and urine (author's transl)]. PMID- 6267157 TI - Biological properties of an influenza A virus-specific killer T cell clone. Inhibition of virus replication in vivo and induction of delayed-type hypersensitivity reactions. AB - We tested two biological properties of a continuously growing mouse cytotoxic T cell line, L4, which is specific for influenza A virus and has been cloned and recloned many times. We previously reported that L4 cells are H-2 restricted and cross-reactive for all type A influenza viruses, whereas they do not recognize type B influenza viruses. They bear Thy-1 and Lyt-2 markers. In the present study, we show that L4 cytotoxic T cells protect mice against a lethal influenza infection on transfer to syngeneic recipients, and reduce virus titers in the lungs of mice challenged with a heterologous type A influenza virus. This provides further support for the active role of cytotoxic T cells in limiting virus replication in influenza infection. We could also demonstrate that the cloned cytotoxic T cells induce a delayed-type hypersensitivity skin reaction in the footpads of mice challenged with live or inactivated influenza virus. This reaction can be observed at 24 h, but has declined by 48 h. A clone of cells derived from L4 that has lost its cytotoxic potential and its ability to recognize infected cells did not induce a delayed-type hypersensitivity reaction in the presence of virus. Thus, cytotoxic T cells actively killing influenza virus-infected cells are able to induce a delayed-type hypersensitivity skin reaction to homologous and heterologous type A influenza viruses. PMID- 6267159 TI - Renal infection with hypercalcemia and increased prostaglandin excretion. PMID- 6267160 TI - Local anesthetics QX 572 and benzocaine act at separate sites on the batrachotoxin-activated sodium channel. AB - We have studied the effect of local anesthetics QX 572, which is permanently charged, and benzocaine, which is neutral, on batrachotoxin-activated sodium channels in mouse neuroblastoma N18 cells. The dose-response curves for each drug suggest that QX 752 and benzocaine each act on a single class of binding sites. The dissociation constants are 3.15 X 10(-5) M for QX 572 and 2.65 X 10(-4) M for benzocaine. Equilibrium and kinetic experiments indicate that both drugs are competitive inhibitors of batrachotoxin. When benzocaine and QX 572 are present with batrachotoxin, they are much more effective at inhibiting Na+ flux than would be predicted by a one-site model. Our results indicate that QX 572 and benzocaine bind to separate sites, each of which interacts competitively with batrachotoxin. PMID- 6267162 TI - Saxitoxin binding in nerves from walking legs of the lobster Homarus americanus. Two classes of receptors. AB - The binding of exchange-labeled saxitoxin (STX) to sodium channels has been investigated in the nonmyelinated fibers of the walking leg nerves of the lobster. The properties of the STX binding site differed systematically among the nerves from different walking legs. The equilibrium dissociation constant for STX binding (KSTX) to the front legs is approximately twice that for the binding to the rear legs; the average ratio of KSTX (front): KSTX (rear) from five separate experiments was 1.80 +/- 0.21 (mean +/- SE). The actual KSTX values ranged from 124.0 to 22.7 nM for the front leg nerves and from 8.6 to 12.7 nM for the rear leg nerves. KSTX values for the middle two walking leg nerves fell between those for the front and rear legs. The inhibitory dissociation constant for tetrodotoxin (KTTX), calculated from tetrodotoxin's inhibition of labeled STX binding, was 3.02 +/- 0.27 nM for the front legs and 2.20 +/- 0.33 nM for the rear legs. The ratio KSTX: KTTX was different in the front and rear leg nerves, being 5.5 and 4.2, respectively. The apparent P pKa of the STX receptor also differed between the two legs, being 4.6 +/- 0.3 for the front legs and 5.1 +/- 0.1 for the rear legs. These results demonstrate that one tissue type in one organism can contain different toxin binding sites. The difference in the receptors can be qualitatively accounted for by the location of an additional negative charge near the receptor site of the rear walking leg. PMID- 6267161 TI - Calcium-regulatory mechanisms. Functional classification using skinned fibers. AB - The primary purpose of this study was to determine whether various agents (adenosine 3-thiotriphosphate [ATP gamma S], trifluoperazine [TFP], troponin I, the catalytic subunit of the cyclic adenosine 3',5'-monophosphate dependent protein kinase [C-subunit], and calmodulin [CaM]) could be used to classify skinned fiber types, and then to determine whether the proposed mechanisms for Ca2+ regulation were consistent with the results. Agents (ATP gamma S, TFP, C subunit, CaM) expected to alter a light chain kinase-phosphatase system strongly affect the Ca2+-activated tension in skinned gizzard smooth muscle fibers, whereas these agents have no effect on skinned mammalian striated and scallop adductor fibers. Troponin I, which is known to bind strongly to troponin C and CaM, inhibits Ca2+ activation of skinned mammalian striated and gizzard fibers but not scallop adductor muscle. The results in different types of skinned fibers are consistent with proposed mechanisms for Ca2+ regulation. PMID- 6267163 TI - Properties of tetraethylammonium ion-resistant K+ channels in the photoreceptor membrane of the giant barnacle. AB - After the offset of illumination, barnacle photoreceptors undergo a large hyperpolarization that lasts seconds or minutes. We studied the mechanisms that generate this afterpotential by recording afterpotentials intracellularly from the medial photoreceptors of the giant barnacle Balanus nubilus. The afterpotential has two components with different time-courses: (a) an earlier component due to an increase in conductance to K+ that is not blocked by extracellular tetraethylammonium ion (TEA+) or 3-aminopyridine (3-AP) and (b) a later component that is sensitive to cardiac glycosides and that requires extracellular K+, suggesting that it is due to an electrogenic Na+ pump. The K+ conductance component increases in amplitude with increasing CA++ concentration and is inhibited by extracellular Co++; the Co++ inhibition can be overcome by increasing the Ca++ concentration. Thus, the K+ conductance component is Ca++ dependent. An afterpotential similar to that evoked by a brief flash of light is generated by depolarization with current in the dark and by eliciting Ca++ action potentials in the presence of TEA+ in the soma, axon, or terminal regions of the photoreceptor. The action potential undershoot is generated by an increase in conductance to K+ that is resistant to TEA+ and 3-AP and inhibited by Co++. The similarity in time-course and pharmacology of the hyperpolarization afterpotentials elicited by (a) a brief flash of light, (b) depolarization with current, and (c) an action potential indicates that Ca++-dependent K+ channels throughout the photoreceptor membrane are responsible for all three hyperpolarizing events. PMID- 6267164 TI - pH dependence of the acetylcholine receptor channel: a species variation. AB - The effects of pH changes on the miniature endplate current (mepc) and on endplate current fluctuations (acetylcholine [ACh] noise) were examined at the neuromuscular junction in vitro in two species of frogs. In Rana pipiens the relationship between the decay time constant of the mepc (tau') and pH had a symmetrical bell shape; the value of tau' being largest at pH 7 and decreasing at more acid or more alkaline pH. In acid pH the mepc amplitude (A) decreased relative to its value at pH 7, and in alkaline pH A increased. In Rana ridibunda a narrower and asymmetric bell-shaped dependence of tau' on pH, having a maximum of pH 5.5, was found. The mepc amplitude was again reduced in acid pH but had a peak at pH 5.5. Also, its value at pH 9 was larger than at pH 7. These results were obtained with a number of different buffers and were not found to be sensitive to the nature of the buffer chosen. By performing ACh-noise analysis we found that in Rana pipiens at acid pH (5.5-5.0), the single channel conductance (gamma) and the single channel open time (tau) were significantly reduced relative to their value at pH 7. However, in Rana ridibunda at acid pH (5.4) gamma was unchanged and tau was markedly increased relative to their values at pH 7. The results can be explained quantitatively by electrostatic interaction between two fixed and titratable ionic groups and a mobile charge in the receptor molecule. The model fits the data for groups having pKs approximately 4.8 and approximately 9.8 for Rana pipiens and approximately 4.6 and approximately 6.3 for Rana ridibunda. The groups can be tentatively identified as amino acid residues; glutamic or aspartic and lysine or tyrosine for Rana pipiens; glutamic or aspartic and histidine for Rana ridibunda. The difference in the fitted values of the other model parameters for these two species can be attributed to differences in the spatial configuration of the charged groups. PMID- 6267166 TI - Transforming proteins of avian retroviruses. PMID- 6267167 TI - Latency in vitro using irradiated herpes simplex virus. AB - Human embryonic fibroblasts infected with u.v.-irradiated herpes simplex virus type 2 (HSV-2, strain 186) and maintained at 40.5 degrees C did not yield detectable virus. Virus synthesis was induced by temperature shift-down to 36.5 degrees C. The induced virus grew very poorly and was inactivated very rapidly at 40.5 degrees C. Non-irradiated virus failed to establish latency at 40.5 degrees C in infected cells. Enhanced reactivation of HSV-2 was observed when latently infected cultures were superinfected with human cytomegalovirus (HCMV) or irradiated with a small dose of u.v. light at the time of temperature shift-down. HCMV did not enhance synthesis of HSV-2 during a normal growth cycle but did enhance synthesis of u.v.-irradiated HSV-2. These observations suggest that in this in vitro latency system, some HSV genomes damaged by u.v. irradiation were maintained in a non-replicating state without being destroyed or significantly repaired. PMID- 6267165 TI - Glycolytic and oxidative metabolism in relation to retinal function. AB - Measurements of lactate production and ATP concentration in superfused rat retinas were compared with extracellular photoreceptor potentials (Fast PIII). The effect of glucose concentration, oxygen tension, metabolic inhibition, and light were studied. Optimal conditions were achieved with 5-20 mM glucose and oxygen. The isolated retina had a high rate of lactate production and maintained the ATP content of a freshly excised retina, and Fast PIII potentials were similar to in vivo recordings. Small (less than 10%) decreases in aerobic and anaerobic lactate production were observed after illumination of dark-adapted retinas. There were no significant differences in ATP content in dark- and light adapted retinas. In glucose-free medium, lactate production ceased, and the amplitude of Fast PIII and the level of ATP declined, but the rates of decline were slower in oxygen than in nitrogen. ATP levels were reduced and the amplitude of Fast PIII decreased when respiration was inhibited, and these changes were dependent on glucose concentration. Neither glycolysis alone nor Krebs cycle activity alone maintained the superfused rat retina at an optimal level. Retinal lactate production and utilization of ATP were inhibited by ouabain. Mannose but not galactose or fructose produced lactate and maintained ATP content and Fast PIII. Iodoacetate blocked lactate production and Fast PIII and depleted the retina of ATP. Pyruvate, lactate, and glutamine maintained ATP content and Fast PIII reasonably well (greater than 50%) in the absence of glucose, even in the presence of iodoacetate. addition of glucose, mannose, or 2-deoxyglucose to medium containing pyruvate and iodoacetate abolished Fast PIII and depleted the retina of its ATP. It is suggested that the deleterious effects of these three sugars depend upon their cellular uptake and phosphorylation during the blockade of glycolysis by iodoacetate. PMID- 6267168 TI - Physical mapping of temperature-sensitive mutations of herpes simplex virus type 2 by marker rescue. AB - The physical mapping of six ts mutations of herpes simplex virus type 2 (HSV-2) is presented. The results were obtained from 14 separate intratypic marker rescue experiments and the analysis of 20 HSV-1/HSV-2 intertypic recombinants. The order of these mutations on the physical map of HSV-2 is unambiguous and correlates almost exactly with the previously published genetic map of Timbury & Calder (1976). One of the mutants studied (HSV-2 ts12) has apparently two distinct conditionally lethal ts mutations, one in the long and the other in the short region of the HSV genome. PMID- 6267170 TI - Expression of Forssman antigen of avian lymphoblastoid cell lines transformed by Marek's disease virus or avian leukosis virus. AB - The expression of Forssman-type heterophile antigen on Marek's disease (MD) virus (MDV)-transformed cell lines, MDCC-MSBI 1, -HP1, -RP1 and -BP1, and avian leukosis virus (ALV)-transformed cell lines, LSCC-1104B1 and -1104X5 was investigated by membrane immunofluorescence and complement-dependent antibody cytotoxicity tests. Forssman antigen was detected on a high percentage of the cells in two ALV-transformed cell lines and on a smaller percentage of splenic lymphocytes from normal chicken. Of the MDV-transformed cell lines tested only the RP1 and BP1 cell lines, derived from transplantable MD tumours, expressed Forssman antigen, while the MSB1 and HP1 cell lines, derived from MD lymphomas, did not. Forssman antigen appears to be unrelated to MD tumour-associated surface antigen (MATSA). PMID- 6267169 TI - Enhancement of transcription of the SV40 genome in mouse embryo cells by pretreatment with 5-iodo-2'-deoxyuridine. AB - Treatment of mouse embryo (ME) cells with 5-iodo-2'-deoxyuridine (IdUrd) before infection with SV40 virus, enhances T-antigen (T-Ag) production as detected by immunofluorescence and complement fixation. Cellular DNA and RNA synthesis are inhibited in both SV40 and mock-infected cells after IdUrd treatment. The analogue pretreatment significantly increases the amount of radiolabelled nuclear and cytoplasmic SV40-specific RNA and the RNA polymerase activity of the viral transcriptional complexes of the Sarkosyl supernatants, suggesting that the enhancement of SV40 T-Ag production in infected pretreated ME cells results from an increased synthesis of early virus RNA. PMID- 6267171 TI - Isolation and characterization of the major capsid protein of bovine papilloma virus type 1. AB - The major capsid protein of bovine papilloma virus type 1 (BPV-1) was isolated by gel filtration following disruption of purified virus particles with guanidine hydrochloride. The capsid protein, VP1, has a mol. wt. of about 53 500. Amino acid composition studies of VP1 showed that it is a highly acidic protein containing almost twice the average number of acidic residues than basic residues. Relatedness was observed between VP1 and the major capsid proteins of simian virus 40 (SV40) and polyoma virus. PMID- 6267172 TI - The polypeptide structure of canine coronavirus and its relationship to porcine transmissible gastroenteritis virus. AB - Canine coronavirus (CCV) isolate 1-71 was grown in secondary dog kidney cells and purified by rate zonal centrifugation. Polyacrylamide gel electrophoresis revealed four major structural polypeptides with apparent mol. wt. of 203800 (gp204), 49800 (p50), 31800 (gp32) and 21600 (gp22). Incorporation of 3H glucosamine into gp204, gp32 and gp22 indicated that these were glycopolypeptides. Comparison of the structural polypeptides of CCV and porcine transmissible gastroenteritis virus (TGEV) by co-electrophoresis demonstrated that TGEV polypeptides corresponded closely, but not identically, with gp204, p50 and gp32 of CCV and confirmed that gp22 was a major structural component only in the canine virus. The close similarities in structure of the two coronaviruses augments the relationship established by serology. PMID- 6267173 TI - Protection of mice by an apathogenic strain HSV-1 against lethal infection by a pathogenic strain of HSV-1. AB - DBA/2 and C57BL/6 mice were infected intraperitoneally with two different strains of herpes simplex virus type 1, HSV-1 ANG and HSV-1 WAL. Unlike HSV-1 WAL, HSV-1 ANG was apathogenic by this mode of infection. Furthermore, infection with HSV-1 ANG protected mice of both inbred strains against infections with lethal doses of pathogenic HSV-1 WAL. This protection was observed when the apathogenic virus was given with the pathogenic virus or 4 to 24 h before it. PMID- 6267174 TI - A glycoprotein specified by spleen focus-forming virus in three cell lines varies on molecular size and peptide composition, but retains both xenotropic and ecotropic MuLV antigenicity. AB - A glycoprotein with an approx. mol. wt. of 55000, encoded by spleen focus-forming virus (SFFV), was detected with an antiserum against xenotropic murine leukaemia virus (MuLV) in various cell lines infected with the Friend strain of SFFV, suggesting that the SFFV-specific RNA coding for gp55 is related to the xenotropic virus. The proteins from three cell lines differed from each other in molecular size and gave different peptide maps. The differences in the gp55 molecules were shown to depend on differences in the SFFV genome, but not on differences in glycosylation or processing of the precursor polypeptides of gp55 in the different cells. These results indicate virus strain specificity of SFFV in gp55 formation. PMID- 6267175 TI - Induction of Epstein-Barr virus early antigen, virus capsid antigen and virus DNA synthesis by mitomycin C. AB - The effect of mitomycin C was tested on Epstein-Barr virus (EBV) antigen and virus DNA synthesis in producer and non-producer cell lines. We found that producer, but not non-producer cell lines, are inducible for early antigen and virus capsid antigen synthesis. Although host DNA synthesis is effectively inhibited by over 99% in the presence of mitomycin C, virus DNA synthesis in the producer lines is unaffected and induced in parallel with the virus antigens. PMID- 6267176 TI - Poliovirus-specific polypeptides in infected HeLa cells analysed by isoelectric focusing and 2D-analysis. AB - Analysis of poliovirus-infected cells by isoelectric focusing in urea resolves at least 25 bands. Combination of isoelectric focusing and sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) in a two-dimensional analysis (2D analysis) revealed a much better resolution than each method separately. By 2D analysis most of the bands could be correlated with the known poliovirus-specific polypeptides generated in the infected cell. With this technique it was possible to determine the apparent isoelectric point (pI) of the identified poliovirus polypeptides. They are in the range from pH 5.6 for polypeptide 7d to pH 8.8 for polypeptide X, which is the most basic found so far. PMID- 6267177 TI - Two-dimensional gel analysis of HSV type 1-induced polypeptides and glycoprotein processing. AB - Two hundred and thirty virus-induced polypeptides have been detected in BHK cells infected with herpes simplex virus type 1 (HSV-1; strain 17) by means of two dimensional gel electrophoresis. The polypeptides have been characterized by both relative mobility following isoelectric focusing and apparent mol. wt. in SDS polyacrylamide gels. Some polypeptides, visualized as a single band on a one dimensional SDS-polyacrylamide gel, were resolved into several spots. Three were identified in Vmw43, the band thought to contain thymidine kinase activity. Not all the observed polypeptides are unique species: some appear to be related and have altered mobilities as a consequence of post-translational modification events. Pulse-chase experiments and treatment of infected cells with neuraminidase suggested that glycoproteins gB, gC and gD contain sialic acid and that synthesis of gB and gD occurs by at least 15 and 10 discrete steps respectively. PMID- 6267178 TI - Adenylic acid: deoxythymidine 5'-phosphotransferase: evidence for the existence of a novel herpes simplex virus-induced enzyme. AB - BHK (dPyK-) cells infected with herpes simplex virus type 1 (HSV-1) contain a virus-induced deoxythymidine (dThd)-phosphorylating enzyme. This enzyme uses AMP as phosphate donor and is called AMP :deoxythymidine 5'-phosphotransferase (or kinase). The enzyme was purified over 1300-fold and was found to be specific for an AMP substrate. It can thus be distinguished from virus-specific deoxypyrimidine kinase (dPyK). It is shown that the two substrates AMP and dThd participate in the reaction at a 1 : 1 molar ratio; the Km for AMP was 2 X 3 muM and for dThd it was 2 X 1 muM. The mol. wt. of the enzyme was estimated to be between 110 000 (by glycerol gradient centrifugation) and 90 000 (by gel filtration). For optimum activity, the phosphotransferase required an alkaline pH, and 37 degrees C; the activation energy of the reaction was 18 450 cal/mol. The appearance of the enzyme after infection parallels that of viral DNA synthesis-related functions. PMID- 6267179 TI - Comparative oligonucleotide analysis of exogenous and endogenous primate type C viruses. AB - RNAs of representative viruses of the exogenous simian sarcoma virus-gibbon ape lymphosarcoma virus (SiSV/GALV) and endogenous baboon virus (BaEV) classes of subhuman primate type C viruses were compared and related to HEL-12 virus, an isolate derived from human embryonic lung cells. The extent of sequence identity between different viral RNA preparations was determined by comparison of fingerprint patterns obtained after electrophoretic separation of RNase T1 resistant oligonucleotides. The studies presented indicate that HEL-12 viral RNA and simian sarcoma-simian associated virus [SiSV(SSAV)] RNA share 90 to 95% of the large oligonucleotides. From 5 to 10% of virus-specific oligonucleotides were detected in each of several virus preparations examined and their occurrence was independent of the cell line on which the virus ws propagated. HEL-12 virus and GALV-SF have 50% unique oligonucleotides in common. These are the same oligonucleotides that are shared between GALV-SF and SisV(SSAV) RNA. Two BaEV isolates, M7 and BILN, and RD114, and BaEV-related endogenous virus of cats, each easily displayed distinguishable oligonucleotides patterns. Large oligonucleotides characteristic for these three endogenous virus isolates were not detected in the fingerprints of HEL-12 virus, SiSV(SSAV) and GALV-SF. PMID- 6267181 TI - A sensitive method for the detection and isolation of recombinants of foot-and mouth disease virus. AB - Recombination between temperature-sensitive (ts) mutants of foot-and-mouth disease (FMD) virus was examined, using an infectious centre technique that was more sensitive (approx. 30-fold) than the conventional virus yield test. The test involved a brief incubation of the mixedly infected cells at the permissive temperature to allow recombination to occur followed by assay at the restrictive temperature to select for those cells in which recombination had occurred. With crosses involving widely separated mutations, as many as 28% of the infected cells produced presumptive recombinant plaques. Since each plaque was the result of an independent event, large numbers of different presumptive recombinants could be isolated for further study. Analysis of presumptive recombinant plaques from a variety of crosses showed that, in general, the virus produced had the properties expected of recombinants. An approximate correlation was found between genetic distance, as determined in the yield recombination test, and the percentage of recombinant infectious centres observed. The phenomenon was very sensitive to the balance between the input multiplicities of the two parent viruses and occurred very early in virus replication. The test has considerable potential for the study of genetic interactions in FMD virus, but it would be surprising if this potential was limited to picornaviruses. PMID- 6267180 TI - Alterations in peptide structure of vesicular stomatitis virus mutant and its central nervous system isolate. AB - Gradient SDS-polyacrylamide gel electrophoresis (PAGE) and proteolytic digestions were utilized to examine the virion proteins of two isolates of wild-type vesicular stomatitis virus (WT-VSV), WTATCC from the American Type Culture Collection and WTGL and Glasgow, as well as temperature-sensitive (ts) mutant ts G31 and a central nervous system (CNS) isolate of ts G31 designated ts G31BP. The WTATCC M protein differed in electrophoretic mobility and in its tryptic or chymotryptic peptide maps from the 125I-labelled M proteins in WTGL, ts G31 or ts G31BP. The M protein in the latter three viruses appeared identical using either tryptic or chymotryptic digestion procedures; however, limited digestion with V8 protease revealed a difference between the M protein of ts G31 and both WTGL and ts G31BP M proteins. The L, NS and G proteins all had identical tryptic and chymotryptic peptide maps in WTGL, ts G31 and ts G31BP virions. The N protein, however, was demonstrated to be distinctly different in the WTGL virion when compared with the ts G31 (or ts G31BP) virion by its tryptic peptide map. In addition, limited proteolytic digestion of the 125I-labelled N proteins revealed a different peptide structure in ts G31BP compared to N proteins of ts G31 or WTGL. The altered N protein in the CNS isolate, ts G31BP, is discussed in terms of its altered in vivo phenotype of labile viral RNA, and its potential role in the unique CNS disease associated with this virus. PMID- 6267182 TI - Interference induced in GL-V3 monkey kidney cells by rabies virus strains. AB - Resistance to superinfection with vesicular stomatitis virus (VSV) occurred in GL V3 monkey kidney cells infected with the CVS-11, Pitman Moore, LEP Flury, but not the ERA strain of rabies virus. Specific immunofluorescent staining of intracellular rabies antigen showed that the number and size of fluorescent foci increased after the onset of interference, and that this was paralleled by increasing yields of infectious virus. Although CVS-11 and ERA differed in their ability to induce interference, the virus yields from monolayers infected with either strain were similar. Interference apparently had no effect on the replication or dissemination of the inducing virus, and seems unrelated to the long incubation period or aberrant forms of infection in vivo. PMID- 6267183 TI - Poly(A) polymerase activity in human rotavirus. AB - A poly(A) polymerase enzymic activity was found in partially purified preparations of a human rotavirus. The activity was demonstrated using conditions similar to those utilized for the detection of the poly(A) polymerase previously described in reovirus (incubation at 43 degrees C in 70 mM-tris buffer pH 7.5 containing 12 mM-Mn2+). The enzymic activity was associated only with complete, double-shelled particles. Characterization of the poly(A)-containing product of the in vitro reaction by gel filtration on Sephadex G-100, followed by chromatography on DEAE-cellulose in the presence of 7 M-urea, showed that it is composed of oligonucleotides of a chain length similar to, or slightly larger than, those observed in reovirus. PMID- 6267184 TI - Protein synthesis in cells infected with bovine rotavirus. AB - Bovine rotavirus was found to multiply efficiently in LLC-MK2 cells, a continuous line of rhesus monkey kidney, with a growth cycle which was essentially completed within 9 h after infection. The presence of low concentrations of trypsin (10 microgram/ml) in the virus inoculum was essential for infectivity. Polyacrylamide gel electrophoresis of infected cell extracts demonstrated the synthesis of at least eight virus-specific polypeptides 6 h post-infection with mol. wt. ranging from 102 X 10(3) to 29 X 10(3). Six polypeptides (about p102K, p91K, p84K, p37K and p34K) were identified as structural components of the virion. Two other polypeptides (54K and p29K) were identified as non-structural components. The synthesis of non-structural polypeptides appeared to precede that of the structural proteins. Pulse-chase experiments showed only one minor post translation modification of the virus-specified proteins, namely an increase in the mobility of the 29K polypeptide. PMID- 6267185 TI - Absence of activated murine leukaemia virus in x-irradiated CBA/H-T6crc mice. AB - CBA/H-T6Crc mice, a substrain that does not normally express demonstrable levels of murine leukaemia virus (MuLV) and has a low natural incidence of leukaemia, were examined for evidence of virus activation at various times following X irradiation. Although X-irradiation caused a high incidence of leukaemia, no ecotropic, xenotropic or recombinant MuLV was detected by in vitro co-cultivation of bone marrow, spleen and thymus cells from pre-leukaemic and leukaemic animals with selectively permissive cell lines followed by indirect immunofluorescence for MuLV group-specific (gs) antigen. These results, therefore, are not consistent with the hypothesis that endogenous viruses are the universal aetiological agents of leukaemia. PMID- 6267186 TI - Characterization of candidate adenovirus 37 by SDS-polyacrylamide gel electrophoresis of virion polypeptides and DNA restriction site mapping. AB - A new human adenovirus has been isolated from patients with keratoconjunctivitis and/or genital infection since 1976. This adenovirus, designed candidate adenovirus 37 (Ad 37) is serologically distinct but related to Ad 10, 13, 19, and 30 (see the accompanying paper by de Jong et al). SDS-Polyacrylamide gel electrophoresis of Ad 37 virion polypeptides showed that this adenovirus is a member of subgroup D. DNA restriction endonuclease analysis of DNA from Ad 37 and related serotypes belonging to subgroup D showed that Ad 37 is a new genome type belonging to subgroup D but clearly distinct from the 20 serotypes classified into this subgroup. PMID- 6267187 TI - Antibody response to cytomegalovirus: a comparison between adult patients with neurological disease and uncomplicated infection. AB - Cytomegalovirus (CMV) infection in adults can cause neurological diseases such as the Guillain--Barre syndrome (GBS) and myelitis. The mechanism leading to the development of neurological damage is, however, still unknown. We have investigated the possibility that an abnormal humoral immune response, either weak or hyperactive, could be the cause. The antibody response of four patients with a primary CMV followed by neurological symptoms was compared to that of four age-matched controls with an uncomplicated infection. IgG and IgM antibodies to CMV early antigens (EA), late antigens (LA), and IgG antibodies to CMV immediate early antigens (IEA) were measured in consecutive serum samples. Comparison of titers indicated a longer time lapse between the onset of CMV infection and the development of symptoms in the group with neurological disease. We found no conclusive evidence of an abnormal humoral immune response to CMV in the patients with neurological disease compared to the patients with an uncomplicated infection. PMID- 6267188 TI - The risk of nosocomial hepatitis A and B virus infections from patients under care without isolation precaution. AB - The risk of nosocomial viral hepatitis cross-infection was investigated in a prospective study of 248 adult patients hospitalized in the Infectious Diseases Hospital of Athens for acute viral hepatitis. They were followed-up clinically, biochemically, and serologically for 100 to 250 days after admission to the Hospital. Commercially available radioimmunoassays were used for the detection of the surface antigen of HBV (HBsAg), its antibody (Anti-HBs), and antibody to the core of the HBV (Anti-HBc), and the IgG and IgM antibodies to the HAV. Clinical, biochemical, or serological indications of hospital cross-infection were not detected in any of the 21 susceptibles to HAV infection or among the 46 susceptibles to HBV infection during the follow-up period, although all of them had ample opportunity for cross-infection through close contact to acutely ill patients. These data provide further evidence that HBV and HAV are not easily transmitted from patients hospitalized for acute viral hepatitis to other susceptible patients sharing wards, and indicate that there is need for reconsideration of the present strategy of hospitalization and care of acutely ill viral hepatitis patients. PMID- 6267189 TI - Viral hepatitis in southeast Asian refugees. AB - Five hundred sixty-four Vietnam refugees were studied for past or present infection with hepatitis A and B virus (HAV and HBV) by sensitive serological assays for hepatitis B surface and e-antigen and antibodies to HBsAg, HBeAg, HBcAg, and HAV. Fifteen percent of the men and 6% of the women were HBsAg positive. Of these 66% were also positive for HBeAg. Serum transaminase values did not effectively differentiate between the infectious HBeAg carriers and the less infectious anti-HBe carriers. The HBsAg carrier rate did not increase by age after infancy, and among children, carriers clustered around HBsAg carrier mothers only. In contrast, the distribution of antibodies to the three HBV associated antigens suggested continuous exposure throughout childhood, and a 90% prevalence rate was found at the age of 20 years. Screening for HBeAg in this new population group is necessary if appropriate precautions are to be taken, and if medical management of these patients is to be optimal. The prevalence of antibody to hepatitis A increases with age to 90% at 15 years. Among anti-HAV-positive children and adults IgM- anti-HAV was found in 8% of the children and none of the adults, indicating that only a few children may be in an infectious stage at the time of study, and therefore no specific prophylactic precautions are necessary. PMID- 6267190 TI - Experimental studies of acute and recurrent herpes simplex virus infections in the murine heart and dorsal root ganglia. AB - The multiplication of HSV-1 and HSV-2 strains in the heart and the corresponding dorsal root ganglia (DRG) was examined in experimentally infected mice. Infectious HSV-1 was recovered from the heart between the second and fourth day after inoculation and 3 days later from the DRG. Both the heart and DRG yielded infectious HSV-2 from the fourth to the twenty-first day after inoculation. The HSV-2, but not the HSV-1, induced recrudescent disease in chronically infected mice up to 18 months after inoculation. These affected mice showed signs of disease similar to those observed during the acute phase of the primary infection. During the recrudescent disease, infectious HSV-2 was recovered both from the heart and DRG. The possibility of using this experimental model for investigating long-term human cardiopathies is discussed. PMID- 6267191 TI - Solid-phase radioimmunoassay of serum IgG, IgM, and IgA antibodies to cytomegalovirus. AB - A radioimmunoassay (RIA) using polystyrene beads as the solid phase for cytomegalovirus (CMV) antigen and iodinated immunosorbent purified anti-human IgG, IgM, and IgA as indicator antibodies was developed for the detection of immunoglobulin class-specific antibodies to CMV. An antigen prepared from extracellular virus was essential for reliable results, and a preparation ultracentrifuged and sonicated twice was better than a crude antigen. The optimal antigen gave low cpm values with a negative reference serum, resulting in cpm ratios of 10 or higher between early convalescent phase serum and negative reference serum. Of six patients with an increase in CMV CF titres, all six had an increase in RIA IgG titres, four had an increase in IgA titres, and all had IgM antibodies. The IgG titres were high, up to 1/64,000. In a group of 17 infants negative in CMV CF test, 14 had CMV IgG antibodies in RIA test, indicating mainly low levels of maternal antibodies. In six of seven patients with CMV isolations from urine specimens, an increase in IgG or IgA titres or the presence of IgM antibodies was found, and only one of these patients had an increase in CMV CF titre. The specificity of the developed CMV RIA test was further demonstrated by detecting no significant increase in RIA titres in serum specimens of patients with primary herpes simplex infection, chickenpox, herpes zoster, or infectious mononucleosis. PMID- 6267192 TI - Neurochemical effects of some ergot derivatives: a basis for their antiparkinson actions. AB - Bromocriptine and the two ergoline derivatives, CQ 32-084 and CM 29-712, exert dopamine-like effects in experimental models and have been shown to possess antiparkinsonian activity. Biochemical investigations indicate that they differ in their specificity towards the different dopamine receptor types and, in addition, interact with other neurotransmitter receptors. Bromocriptine appears to be a potent agonist at D2-receptors. Furthermore, it blocks adenylate cyclase coupled serotonin receptors and antagonizes central alpha-adrenergic receptors. The two ergoline derivatives are multiple agonists. CQ 32-084 stimulates both D1- and D2-, and CM 29-712 only D1-receptors. In addition, both compounds stimulate adenylate cyclase coupled serotonin receptors and antagonize central alpha adrenergic receptors. PMID- 6267193 TI - Kinetic and magnetic resonance studies of substrate binding to galactose oxidase copper(II). AB - Alcohol substrate binding to the copper-containing enzyme galactose oxidase (GOase) has been studied by kinetic competition against cyanide and fluoride, 13C nmr relaxation, and esr competition experiments. The 13C nmr spectra of the substrate beta-O-methyl-D-galactopyranoside (beta-O-me-gal) show no apparent paramagnetic relaxation rate enhancement that could be attributed to innersphere equatorial binding of this molecule at the Cu(II) center. Moreover, the kinetics observed when CN- or F- are used as inhibitors of GOase with beta-O-me-gal as the substrate suggest that these anions act as apparent non-competitive inhibitors; the binding of the substrates beta-O-me-gal and O2 is not hindered per se, but the catalytic activity of the enzyme substrate complex is greatly decreased. The esr competition data also confirm that, in the absence of O2, CN- and beta-O-me gal do not compete for the same GOase binding site. Previously reported esr and 19F nmr data show that CN- binds to the GOase Cu(II) at an equatorial coordination site, as does the F- detected in esr experiments. Thus, the results from the various competition experiments supports a model in which alcohol substrates bind outersphere to the GOase Cu(II), or, possibly, to an axial site. PMID- 6267194 TI - Is Na + ATPase a myelin-associated enzyme? AB - The Na + K ATPase activity associated with purified myelin has been investigated. On the basis of marker enzyme studies, the Na + K ATPase activity of myelin was higher than could be accounted for by microsomal contamination. Fractions prepared from white matter-enriched areas of rat brain showed a threefold enrichment in Na + K ATPase activity in myelin as compared with the white matter homogenate. The ATPase activity in myelin was stimulated fourfold by treatment with sodium deoxycholate, but the activity in the whole brain homogenate and the microsomal fraction was only doubled. This discontinuity temperature for Na + K ATPase activity was significantly higher for the myelin fraction (29 degrees C) than for the microsomal fraction (21 degrees C), but the energies of activation, both above and below the discontinuity temperature, were the same for both fractions, Myelin Na + K ATPase had a lower affinity for strophanthidin than the microsomal enzyme, but both fractions were inhibited to the same extent by 10-3 M strophanthidin. The evidence thus indicated that much of the ATPase activity of myelin is not the result of microsomal contamination. Although the possibility of axolemmal contamination cannot be ruled out conclusively, indirect evidence suggest that this is not a significant factor and that Na + K ATPase may be a myelin-associated enzyme. PMID- 6267195 TI - Benzodiazepine receptors on primary cultures of mouse astrocytes. AB - Benzodiazepines bind to glial membranes on a single type of site, with a high affinity (KD = 5 x 10(-9) M) on about 100 fmol of sites per mg protein. The number of binding sites is increased when the membranes are treated with Triton X 100. Antiepileptic drugs such as clonazepam and phenobarbital and hypnotic drugs such as Ro-11-3128 and Ro-11-6896 are able in pharmacological concentrations to displace [3H]flunitrazepam from its glial binding sites. PMID- 6267196 TI - Characterization of gamma-aminobutyric acid binding sites on crude synaptic membranes. AB - [3H]GABA binding to crude synaptic membranes of rat brain was studied in an attempt to identify GABA binding to its synaptic receptor in the presence of Na+. Membrane vesicles prepared from crude synaptic membrane fractions were useful as a tool to differentiate synaptic GABA receptors from GABA uptake sites. The crude synaptic membranes treated with Triton X-100 [membranes (TX)] involved two classes of GABA binding sites (KD = 38.7 and 78.0 nM) in the absence of Na+, but the high-affinity sites disappeared in the presence of Na+ and a single class of GABA binding sites (KD = 75.0 nM) was detected. The failure to detect an active uptake of [3H]GABA into the vesicles prepared from membranes (TX) suggests that the [3H]GABA binding in the presence of Na+ was related to synaptic GABA receptors. It is probable that Na+ could mask the presence of the high-affinity class of GABA receptor. PMID- 6267198 TI - Substantia nigra gamma-aminobutyric acid receptors in Huntington's disease. AB - The specific binding of [3H]gamma-aminobutyric acid (GABA) to nigral GABA receptors has been studied in postmortem brains from controls and patients with Huntington's disease (HD). A specific increase in the number of high-affinity binding sites for [3H]GABA was observed in HD patients, analogous to changes observed in rat substantia nigra [3H]GABA binding after striatal kainic acid (KA) lesion. The results provide further support for the striatal KA lesion in the rat as an animal model of HD. The implications of the results for the proposed therapeutic potential of GABA agonists in HD are discussed. PMID- 6267197 TI - Postnatal development of synaptic glycine receptors in normal and hyperglycinemic rats. AB - The postnatal development of glycine synaptic receptors has been studied. Strychnine binding to the synaptic membrane fraction is very low at birth, increases thereafter, and reaches adult values at the 15th day in the brain, and at the 30th day in the spinal cord. Throughout postnatal development, there are more glycine receptors in the spinal cord than in the brain. The development of receptors in the spinal cord displays a pattern similar to that reported previously for the glycine reuptake system in spinal cord slices and in the activity of spinal cord glycine synthase. In rats with experimental hyperglycinemia strychnine binding to spinal cord glycine receptors increases much more rapidly, reaching a level 1.5 times the control value by day 10. When the hyperglycinemia was induced after the 10th postnatal day, however, no effect on the glycine receptors was observed. This increased number of receptors could be explained by an effect of glycine on the synaptic stabilisation process. No changes in the KD for strychnine were observed either during postnatal development or in hyperglycinemic rats. The KD remained approximately 10 nM in the spinal cord and 50 nM in the brain. Results are discussed with respect to the ontogeny of glycinergic synapses and the pathogenesis of nonketotic hyperglycinemia. PMID- 6267199 TI - [3H]Propyl beta-carboline-3-carboxylate as a selective radioligand for the BZ1 benzodiazepine receptor subclass. AB - Ethyl beta-carboline-3-carboxylate (beta-CCE) is a mixed-type inhibitor of [3H]flunitrazepam ([3H]FNM) binding to benzodiazepine receptors in noncerebellar regions of rat brain. These findings may represent the presence of either receptor multiplicity or negative cooperativity among benzodiazepine receptors. [3H]Propyl beta-carboline-3-carboxylate ([3H]PrCC) has previously been shown to bind specifically to benzodiazepine receptors of rat cerebellum. In the present study we found no indication of the presence of true negative cooperativity among benzodiazepine receptors when [3H]PrCC was used as radioligand. However, we observed that [3H]PrCC labelled only 57% of [3H]FNM binding sites in rat hippocampus (Bmax values) and 71% in rat cerebral cortex, whereas the number of receptors labelled by both ligands was equal in the cerebellum. Hofstee analyses of the shallow inhibition curves seen in hippocampus and cerebral cortex when [3H]FNM binding was inhibited by beta-CCE indicate that beta-CCE and some other beta-carboline-3-carboxylate derivatives interact preferentially with a subclass of receptors, and that the percentage of this subclass is equivalent to the number of receptors labelled by [3H]PrCC. We conclude that [3H]PrCC at low concentration (0.3-0.4 X 10(-9) M) labels a subclass of benzodiazepine receptors, BZ1, while another class, BZ2 receptors, are not labelled by [3H]PrCC when filtration assays are used. By parallel determinations of the proportion between [3H]FNM and [3H]PrCC binding we calculated the percentage of BZ1 receptors in several regions of rat, guinea pig and calf brain and in mouse forebrain. The values ranged from approximately 50% in hippocampus to 90% in the guinea pig pons. PMID- 6267200 TI - Activation of (Na+, K+)-ATPase by nanomolar concentrations of GM1 ganglioside. AB - GM1 ganglioside binding to the crude mitochondrial fraction of rat brain and its effect on (Na+, K+)-ATPase were studied, the following results being obtained: (a) the binding process followed a biphasic kinetics with a break at 50 nM-GM1; GM1 at concentrations below the break was stably associated, while over the break it was loosely associated; (b) stably bound GM1 activated (Na+, K+)-ATPase up to a maximum of 43%; (c) the activation was dependent upon the amount of bound GM1 and was highest at the critical concentration of 20 pmol bound GM1 X mg protein 1; (d) loosely bound GM1 suppressed the activating effect on (Na+, K+)-ATPase elicited by firmly bound GM1; (e) GM1-activated (Na+, K+)-ATPase had the same pH optimum and apparent Km (for ATP) as normal (Na+, K+)-ATPase but a greater apparent Vmax; (f) under identical binding conditions (2 h, 37 degrees C, with 40 nM substance) all tested gangliosides (GM1, GD1a, GD1b, GT1b) activated (Na+, K+) ATPase (from 26-43%); NeuNAc, sodium dodecylsulphate, sulphatide and cerebroside had only a very slight effect. It is suggested that the ganglioside activation of (Na+-K+)-ATPase is a specific phenomenon not related to the amphiphilic and ionic properties of gangliosides, but due to modifications of the membrane lipid environment surrounding the enzyme. PMID- 6267201 TI - Characterization of the binding of the GABA agonist [3H]piperidine-4-sulphonic acid to bovine brain synaptic membranes. AB - The binding of radioactive piperidine-4-sulphonic acid ([3H]P4S) to thoroughly washed, frozen, and thawed membranes isolated from cow and rat brains has been studied. Quantitative computer analysis of the binding curves for four regions of bovine brain revealed the general presence of two binding sites. In these brain regions less satisfactory computer fits were obtained for receptor models showing one or three binding sites or negative cooperativity. With the use of Tris citrate buffer at 0 degree C the two affinity classes for P4S in bovine cortex membranes revealed the following binding parameters: KD = 17 +/- 7 nM (Bmax = 0.15 +/- 0.07 pmol/mg protein) and KD = 237 +/- 100 nM (Bmax = 0.80 +/- 0.20 pmol/mg protein). Heterogeneity was also observed for association and dissociation rates of [3H]P4S. The slow binding component (kon = 5.6 X 10(7) or 8.8 X 10(7) M-1 min-1, koff = 0.83 min-1, and KD = 14.7 or 9.4 nM, determined by two different methods in phosphate buffer containing postassium chloride) corresponds to the high-affinity component of the equilibrium binding curve (KD = 11 nM, Bmax = 0.12 pmol/mg protein in the same buffer system). The association and dissociation rates for the subpopulation of rapidly of dissociating sites, apparently corresponding to the low-affinity sites, were too rapid to be measured accurately. The binding of [3H]P4S appears to involve the same two populations of sites with Bmax values similar to those for [3H]GABA binding to the same tissue, although the kinetic parameters for the two ligands are somewhat different. Furthermore, comparative studies on the inhibition of [3H]P4S and [3H]GABA binding by various GABA analogues, strongly suggest that P4S binds to the GABA receptors. The different effects of P4S and GABA on benzodiazepine binding are discussed. PMID- 6267202 TI - Effects of sodium and bicarbonate ions on gamma-aminobutyric acid receptor binding in synaptic membranes of rat brain. AB - Crude synaptic membranes treated with Triton X-100 (TX) bound gamma-aminobutyric acid (GABA) to two classes of receptor site in Na+-free 10 mM-Tris-sulfate buffer (pH 7.4), but to only a single class of receptor site in 10 mM Tris-sulfate buffer (pH 7.4), containing 150 mM-NaCl. The high-affinity receptor site in TX membranes was specifically masked in the presence of Na+. However, TX membranes incubated in Krebs-Ringer bicarbonate solution (pH 7.4) bound GABA to two classes of receptor site despite the presence of Na+. It was found that addition of bicarbonate ions to the Na+-containing 10 mM-Tris-sulfate buffer (pH 7.4) could restore that high-affinity class of GABA receptors, rendering both classes detectable. This finding suggests that both Na+ and HCO-3 may have a regulatory function on GABA binding to the receptor. PMID- 6267203 TI - Sequestration of 125I-labeled beta nerve growth factor by embryonic sensory neurons. AB - Nerve growth factor (NGF) binds to two specific receptors on sensory nerve cells. These two receptors are characterized by different equilibrium dissociation constants. The higher affinity (type I) receptors have an equilibrium dissociation constant of 3.3 X 10(-11) M. The lower affinity (type II) receptors have an equilibrium dissociation constant of 1.7 X 10(-9) M. These two receptors are not a result of negative cooperativity, but apparently are different receptors. At 22 degrees C the rate of association is 1 X 10(7) M-1 S-1 and the rates of dissociation are 6.5 X 10(-4) S-1 (type I) and 3.2 X 10(-2) S-1 (type II). After binding, a time-dependent process occurs that makes that NGF inaccessible to the external milieu (sequestered). The sequestration process is energy-dependent, but apparently temperature-independent. The data suggest that only the type I receptors are involved in the sequestration process. This process is similar to that observed on sympathetic neurons and may be the first step in the internalization of NGF by responsive cells. PMID- 6267204 TI - Oligodendroglial glycerophospholipid synthesis: incorporation of radioactive precursors into ethanolamine glycerophospholipids by calf oligodendroglia prepared by a Percoll procedure and maintained in suspension culture. AB - Oligodendroglia prepared from minced calf cerebral white matter by trypsinization at pH 7.4, screening, and isosmotic Percoll (polyvinylpyrolidone-coated silica gel) density gradient centrifugation survived in culture on polylysine-coated glass, extending processes and maintaining phenotypic characteristics of oligodendroglia. In the present study, ethanolamine glycerophospholipid (EGP) metabolism of the freshly isolated cells was examined during short-term suspension culture by dual label time course and substrate concentration dependence experiments with [2-3H]glycerol and either [1,2-14C]ethanolamine or L [U-14C]serine. Rates of incorporation of 3H from the glycerol and of 14C from the ethanolamine into EGP were constant for 14 h. In medium containing 3 mM-[1,2 14C]ethanolamine and 4.8 mM-[2-3H]glycerol, rates of incorporation of 14C and 3H into diacyl glycerophosphoethanolamine (diacyl GPE) were similar. Under the same conditions, 3H specific activities of alkylacyl GPE and alkenylacyl GPE were much lower than 14C specific activities, likely as a result of the loss of tritium during synthesis of these forms of EGP via dihydroxyacetone phosphate. L-[U 14C]serine was incorporated into serine glycerophospholipid (SGP) by base exchange rather than de novo synthesis. 14C from L-[U-14C]serine also appeared in EGP after an initial lag period of several hours. Methylation of oligodendroglial EGP to choline glycerophospholipid (CGP) was not detected. PMID- 6267205 TI - Characterization of receptors for cholecystokinin and related peptides in mouse cerebral cortex. AB - The characteristics of cholecystokinin (CCK) binding to its receptors in a particulate membrane fraction of mouse cerebral cortex were studied by employing biologically active radioiodinated CCK prepared by conjugation with 125I-Bolton Hunter (125I-BH) reagent. At 24 degrees C binding was rapid, reversible, and linearly related to protein content. Binding was maximal at acidic pH (6.5) and reduced by the presence of monovalent cations. Under physiological conditions (pH 7.4, 118 mM-NaCL, 4.7 mM-KCl) Scatchard plots of CCK binding were linear with a KD value of 1.27 nM and binding capacity of 115 fmol/mg protein. Optimal binding required the presence of both Mg2+ and EGTA, and was inhibited by the addition of micromolar concentrations of Cu2+ (ID50 = 30 microM). The cortical receptor recognized all major forms of CCK, with an order of potency of: cholecystokinin octapeptide (CCK8) greater than CCK greater than cholecystokinin tetrapeptide (CCK4). Desulfated cholecystokinin octapeptide (dCCK8) had a 10-fold lower affinity than CCK8. Dibutyryl cyclic GMP, a potent competitive inhibitor of CCK binding to receptors in pancreas, was not a specific inhibitor of CCK binding to brain receptors. These present results support the concept that CCK may function as a regulatory peptide in brain, and that the cortical CCK receptor is different from the receptors mediating the peripheral action of CCK. PMID- 6267206 TI - Ethanol alters kinetic characteristics and function of striatal morphine receptors. AB - Morphine was shown to promote dopamine (DA) synthesis and release in mouse striatum, but mice rendered tolerant and dependent on ethanol were found to be less responsive to morphine's effects on striatal DA metabolism than control animals. Ethanol feeding also produced a change in the affinity of striatal "opiate" receptors for [3H]dihydromorphine, and these ethanol-induced receptor changes may be responsible for the altered biological effect of morphine. PMID- 6267207 TI - Morphology and distribution of cytoplasmic inclusions in adrenoleukodystrophy. AB - We report some additional observations on the pathognomonic cytoplasmic inclusions in a typical case of adrenoleukodystrophy (ALD). Study of the linear inclusions by means of tilt-stage electron microscopy indicated that they represent trilaminar sheet-like structures distinct from materials seen in various other storage disorders. This study emphasizes that the inclusions in the adrenal and testicular parenchymal cells morphologically differ from those in the brain macrophages. In the latter they occur as membrane-bound discrete structures while in the parenchymal cells they are always seen lying free in the cytoplasm and associated with cleft-like spaces. This morphologic variation of the inclusions is noteworthy and probably reflects a biochemical difference in the storage materials in these two most severely affected organs. In addition, this study demonstrates the presence of linear inclusions within macrophages in otherwise normal-appearing liver, spleen, thymus and also in the renal tubular cells. These findings suggest that the abnormal materials containing very long chain fatty acids enter the blood stream and become sequestered in the reticuloendothelial system and possibly are also excreted in the urine. Detection of these abnormal fatty acids in blood and urine may simplify diagnosis of ALD. PMID- 6267208 TI - Differential effects of TEA and cations on outward ionic currents of cat motoneurons. PMID- 6267209 TI - Discharge characteristics and stretch sensitivity of jaw muscle afferents in the monkey during controlled isometric bites. PMID- 6267210 TI - Mechanisms of pattern generation underlying swimming in Tritonia. I. Neuronal network formed by monosynaptic connections. PMID- 6267211 TI - Cross-Correlation Analysis of Interneuronal Connectivity in cat visual cortex. PMID- 6267212 TI - Organization of cat visual cortex as investigated by cross-correlation technique. PMID- 6267214 TI - Comparison of responses to moving and stationary stimuli in cat striate cortex. PMID- 6267213 TI - Receptive-field structure in cat striate cortex. PMID- 6267215 TI - Postural changes alter synaptic interactions between nonspiking interneurons and motor neurons of the locust. PMID- 6267216 TI - Changes in translation of synaptic excitation to dentate granule cell discharge accompanying long-term potentiation. I. Differences between normal and reinnervated dentate gyrus. PMID- 6267217 TI - Changes in translation of synaptic excitation to dentate granule cell discharge accompanying long-term potentiation. II. An evaluation of mechanisms utilizing dentate gyrus dually innervated by surviving ipsilateral and sprouted crossed temporodentate inputs. PMID- 6267218 TI - Active zone at Aplysia synapses: organization of presynaptic dense projections. PMID- 6267219 TI - Visual properties of neurons in a polysensory area in superior temporal sulcus of the macaque. PMID- 6267220 TI - Different efficacies of d- and l-gamma-amino-beta-hydroxybutyric acids in GABA receptor and transport test systems. PMID- 6267221 TI - [3H]Diazepam binding in mammalian central nervous system: a pharmacological characterization. AB - Two types of benzodiazepine binding sites for [3H]diazepam in mammalian central nervous tissue were identified using selective in vitro tissue culture and in situ kainic acid lesion techniques. These two binding sites were pharmacologically distinguished by differential displacement of the [3H]diazepam radioligand using the centrally active benzodiazepine, clonazepam, and the centrally inactive benzodiazepine, RO5-4864. Clonazepam-displaceable binding sites were found to be located principally on neuronal membranes, while RO5-4864 displaceable binding sites were found to be located on non-neuronal elements. These pharmacological distinctions can be used to characterize the predominant cell types which bind benzodiazepines in nervous tissue. It is suggested that one quantitative measure of different cell populations is the ratio of clonazepam- to RO5-4864-displaceable [3H]diazepam binding within a single neuronal tissue simple. PMID- 6267223 TI - On the role of Ca2+ in the transmitter choice made by cultured sympathetic neurons. PMID- 6267222 TI - On the role of cyclic nucleotides in the transmitter choice made by cultured sympathetic neurons. AB - Previous investigations have established that electrical activity or chronic depolarization influences the development of neonatal rat sympathetic neurons in dissociated cell culture. Depolarization reduces their ability to respond to a cholinergic inducing factor produced by non-neuronal cells, allowing normal adrenergic differentiation to proceed (Walicke, P., R. Campenot, and P. Patterson (1977) Proc. Natl. Acad. Sci. U. S. A. 74: 5767-5771). The present study examines whether the developmental effects of depolarization are mediated through cyclic nucleotides. Addition of dibutyryl cAMP, dibutyryl cGMP, adenosine, prostaglandin E1, and cholera toxin all raise neuronal cyclic nucleotide levels and qualitatively mimic the developmental effects of depolarization. However, the quantitative decrease in acetylcholine production caused by these cyclic nucleotide agents is much smaller than that caused by depolarization. Short (48 hr) exposures to the cyclic nucleotide derivatives do not alter transmitter synthesis, indicating that long term developmental changes are involved. Chronic depolarization with elevated K+ increases neuronal cAMP 2-fold but has little effect on cGMP. The increase in cAMP is maintained during several weeks of depolarization and is present as early as the 3rd day in vitro, preceding the significant alterations in adrenergic and cholinergic differentiation. Exposure to 2 mM theophylline also increases neuronal cAMP, but in contrast to the other agents, it enhances cholinergic differentiation. In combination with elevated K+, theophylline further increases neuronal cAMP but still favors cholinergic differentiation. Thus, although cAMP satisfies some criteria for being the second messenger in the developmental effects of depolarization, several findings are consistent with the nucleotide playing a central role: (i) Depolarization has much larger effects on transmitter choice than the cyclic nucleotide agents and (ii) theophylline can uncouple cyclic nucleotide levels from the developmental events. PMID- 6267224 TI - Enhancement by anesthetic and convulsant barbiturates of GABA binding to rat brain synaptosomal membranes. AB - All of the anesthetic (amylobarbitone, butobarbitone, pentobarbitone, phenobarbitone, and secobarbitone) and convulsant (5-ethyl-5(3'-methylbut-2-enyl) barbituric acid (3M2B) and 5-ethyl-5-(2'-cyclohexylidene-ethyl) barbituric acid (CHEB) barbiturates tested enhanced the binding of GABA to a carefully prepared P2 membrane fraction from rat brain in a dose-dependent manner. These findings are in agreement with the potentiation of the inhibitory effects of GABA in many neuronal systems by both classes of barbiturates. PMID- 6267225 TI - Characterization of benzodiazepine and gamma-aminobutyric recognition sites and their endogenous modulators. AB - The solubilization and partial purification from rat brain cortex homogenates of [3H]gamma-aminobutyric acid (GABA) and [3H]diazepam recognition sites and of their endogenous modulators (GABA-modulin and an endogenous compound which specifically bound [3H]diazepam) are reported. A high percentage of GABA binding sites (virtually free of benzodiazepine binding sites) was solubilized from homogenates of rat brain cortex incubated at 0 degree C with 1% Triton X-100 and a mixture of protease inhibitors. A large proportion of benzodiazepine binding sites was solubilized in the absence of apparent GABA binding capacity by incubating crude synaptic membrane preparations at 37 degree C with 0.05% Triton X-100. The characteristics of these two solubilized binding sites resemble those of the membrane-bound binding sites. However, unlike the membrane-bound sites, solubilized GABA and benzodiazepine binding sites are insensitive to GABA stimulation, while solubilized GABA binding sites are no longer protected by the benzodiazepines against heat inactivation. These results indicate that GABA and benzodiazepine recognition sites reside in two different molecules which, when bound to membranes, can interact reciprocally and modulate their binding affinity for specific ligands. PMID- 6267226 TI - Glial membrane potentials and their relationship to [K+]o in man and guinea pig. A comparative study of intracellularly marked normal, reactive, and neoplastic glia. PMID- 6267227 TI - Adenosine-stimulated astroglial swelling in cat cerebral cortex in vivo with total inhibition by a non-diuretic acylaryloxyacid derivative. AB - The intact cerebral cortices of cats were exposed in vivo under normothermic conditions and superfused with isotonic artificial cerebrospinal fluid containing added 0.125 mM adenosine. This resulted in chloridecation-rich cerebrocortical swelling which was shown by electron microscopy to be associated with an expanded astroglial compartment. The addition of DCPIB, a non-diuretic acylaryloxyacid analogue of ethacrynic acid and an inhibitor of coupled chloride-cation transport in cerebral cortex in vitro, totally blocked astroglial swelling and the concomitant increases in tissue ion contents. These studies support our previous experiments on the mechanism of formation of astroglial swelling. The pathological consequences of astroglial swelling and the clinical applications of these findings are discussed. PMID- 6267228 TI - Primitive neuroectodermal tumors of childhood. An approach to therapy. AB - Primitive neuroectodermal tumors are found in the cerebrum of children and young adults. The are clinically highly malignant and have rapid course from diagnosis to death. Their microscopic pathology reveals 90% to 95% nondifferentiation, frequent mitoses, and small dark cells with no observable cytoplasm. This paper discusses the treatment of three children with this tumor with a combination of surgery irradiation, and combination chemotherapy. The results of this approach are compared with previous reports in the literature. The average survival in this series is 24 months versus approximately 8 months reported in the literature. PMID- 6267229 TI - Fast attempts at the photodynamic treatment of human gliomas. AB - Photodynamic therapy is based on the capacity of certain substances to preferentially stain neoplastic tissues in respect to healthy tissues, and on the property of such substances to produce cytotoxic agents when excited by light of an appropriate wavelength. The authors demonstrate the first attempts to photoradiant therapy in the treatment of human gliomas utilizing a hematoporphyrin derivative injected i.v. as a sensitizing drug. A He Ne Laser (632,8 nm) was used in order to trigger the photodynamic process. Immediately after surgical removal of the glioma the residual tumoral bed was exposed to the action of the Laser in order to provoke necrosis of the remaining neoplastic cells. Necrosis even if partial of the residual tumor was effected. Better and more definite results may be obtained in the future utilizing a Laser connected with fiber optics consenting an in-depth light penetration. PMID- 6267230 TI - Multiple gliomas of the brain. Report of three cases. PMID- 6267231 TI - The effect of gastrointestinal hormones on the pertechnetate imaging of ectopic gastric mucosa in experimental Meckel's diverticulum. PMID- 6267232 TI - Radionuclide quantitation of left-to right cardiac shunts using deconvolution analysis: concise communication. AB - Quantitative radionuclide angiocardiography (QRAC) was performed with and without deconvolution analysis (DA) in 87 children with various heart disorders. QRAC shunt quantitation was possible without DA in 70% of the cases and with DA in 95%. Among 21 patients with prolonged bolus injections, quantitation of the shunt was possible in 52% of the cases without DA an in all cases with DA. Correlation between oximetry and QRAC with DA was better than between oximetry and QRAC without DA. It is concluded that QRAC with DA is a more reliable, noninvasive means for detection and quantitation of left-to-right cardiac shunts than QRAC without DA. PMID- 6267233 TI - Detection of ectopic gastric mucosa in Meckel's diverticulum and in other aberrations by scintigraphy: ii. indications and methods--a 10-year experience. AB - Ten years' experience with pertechnetate (Tc-99m) abdominal scintigraphy has shown that the method is specifically indicated for the diagnosis and location of ectopic gastric mucosa in a Meckel's diverticulum, in enteric or gastric duplications and cysts, and in Barrett's esophagus. Careful patient preparation is essential, and sequential gamma camera imaging for 1 hr in the anterior projection is advisable, with complementary lateral, upright, and postvoiding views. Nonspecific accumulations of the tracer within tumours, intestinal obstructions, arteriovenous malformations, and the urinary tract can be recognized with the help of the clinical history and can be investigated by other tests. This approach has raised the accuracy of the method above 90%. PMID- 6267234 TI - Pulmonary bleeding diagnosed as an incidental finding during a gated cardiac scan. PMID- 6267235 TI - Effect of lead ingestion on functions of vitamin D and its metabolites. AB - A study of the effect of ingestion of lead on the metabolism and function of vitamin D was carried out in rats fed diets varying in calcium and phosphorus content. The ingestion of 0.82% lead as lead acetate suppressed plasma levels of 1,25-dihydroxycholecalciferol in rats fed either a low phosphorus or a low calcium diet while it had no effect on this parameter in rats fet either a high calcium diet or a normal phosphorus diet. Most important, the ingestion of lead totally blocked the intestinal calcium transport response to cholecalciferol, 25 hydroxycholecalciferol and 1,25-dihydroxycholecalciferol. On the other hand, the ingestion of lead acetate had no influence on the mobilization of calcium from bone, the elevation of serum inorganic phosphorus and in the mineralization of rachitic bone in the same animals. Thus by the feeding of 0.82% lead on the intestinal responses to vitamin D and its metabolites was greatest in animals fed a low calcium or a low phosphorus diet, it was present with all diets tested. PMID- 6267236 TI - Starvation-induced changes of hepatic glucose metabolism in hypo- and hyperthyroid rats in vivo. AB - The role of thyroid hormones in the metabolic adaptation to starvation was investigated in vivo. Glucose production, measured by tracer technique, was enhanced in hyperthyroid (185%) and reduced in hypothyroid (39%) 48-hour starved rats (euthyroid control = 100%). Urinary nitrogen excretion was increased in hyperthyroidism (132%) and decreased in hypothyroidism (70%). Compared with euthyroid controls (=100%) significant alterations for the following regulatory parameters of hepatic gluconeogenesis were observed: 1) tissue cAMP (124%/91%) and protein kinase activation (132%/90%), with a corresponding crossover between pyruvate and P-enolpyruvate (-/+/+/-); 2) pyruvate carboxylase (165%/60%), P enolpyruvate carboxykinase (140%/82%) and fructose-1.6-bis-P-phosphatase activity (99%/61%), and 3) tissue content of the glucogenic amino acids: alanine (187%/66%) and glutamate (187%/88%), aspartate (179%/68%) and glutamate (137%/75%), as well as of oxaloacetate (254%/66%) and malate (164%/104%). The observed alterations in hepatic oligomycine-sensitive oxygen consumption in hyper (161%) and hypothyroidism (51%) were related to the measured concentration of the intermediates of the citric acid cycle, the energy state and the mitochondrial redox state. In summary, the different rates of hepatic glucose production in hyper- and hypothyroid starved rats observed in vivo can be ascribed to 1) cAMP content, 2) gluconeogenic key enzyme activities, 3) glucogenic precursor supply and 4) cofactor (ATP) availability. PMID- 6267238 TI - The development of an acth-induced renal glomerular lesion in Mus musculus. An ultrastructural study. AB - Male house mice (Mus musculus) were injected with 4 international units of ACTH daily for 1, 2, 3 and 4 weeks and with four units daily for four weeks followed by 8 units for 8 days. Light microscopy of kidneys showed a glomerular lesion characterised by the expansion of the mesangium, deposition of PAS positive material in the glomerular mesangium and extraglomerular mesangium hypertrophy of juxtaglomerular cells and a successive increase in oil red-O staining material in the glomerulus. Electron microscopy revealed the progressive accumulation in the mesangial matrix of three morphologically distinct forms of deposits: amorphous, globular and particulate. The accumulation of amorphous deposit apparently is partially responsible for the increased PAS positive staining of the mesangium. Globular (and possibly particulate) deposit probably corresponds to the oil red-O positive material. The evidence suggests that the deposits are extraglomerular in origin, but their chemical nature is unknown. PMID- 6267237 TI - Effects of selected polysaccharides on the bioavailability of pyridoxine in rats and chicks. AB - The effects of cellulose, pectin and bran on the bioavailability of pyridoxine (PN) were examined using rat and chick bioassay methods. Dose-response curves for growth, feed consumption, feed efficiency and either lever pyridoxal 5'-phosphate (PLP) or erythrocyte aspartate aminotransferase (Asp-AT) activity and PLP stimulation in vitro were compared among animals fed experimental diets varying in dietary fiber source and suboptimal levels. of PN. In rats, the observed stimulation of growth and feed efficiency by pectin, as compared to cellulose, at suboptimal PN levels was attributed to increased synthesis of vitamin B-6 intestinal microflora. Diets containing pectin markedly increased the fecal vitamin B-6 content. No difference in liver PLP was detected among rats fed various diets. In chicks, 5% dietary pectin resulted in increased feed consumption, but also diarrhea and depressed growth. Asp-AT activities at the lower level of dietary PN showed a significant (P greater than 0.05) but modest stimulating effect of pectin on the apparent bioavailability of PN. Bran resulted in a 17% bioavailability decrease of PN as indicated by growth and feed consumption data in the chick. However, no difference in Asp-AT activity or in vitro PLP stimulation was detected in comparison of responses from bran-fed chicks with the standard responses. These results suggest that the polysaccharides tested did not have important deleterious effects on the bioavailability of pyridoxine. PMID- 6267239 TI - Malignant histiocytic tumour presenting as a primary uterine neoplasms: a cytochemical and electron microscopy study. AB - A 41-year-old woman was admitted because of uterine bleeding. The diagnosis of malignant histiocytic tumor was suspected from microscopic examination of the material obtained with diagnostic curettage. Total hysterectomy was performed a week later and a complete pathological examination of the specimens was performed. Cytochemical and immunoperoxidase stains and electron microscopy confirmed that the neoplastic cells were derived from histiocytic elements, i.e. from the mononuclear phagocyte system. PMID- 6267240 TI - Trisomy 18 and neurogenic neoplasia. PMID- 6267241 TI - Porencephaly and cytomegalovirus in a surviving monozygotic twin. PMID- 6267242 TI - Partial characterization of ribonuclease (RNase) activity from the isolated and solubilized brush border of Hymenolepis diminuta. AB - The isolated brush border membrane of Hymenolepis diminuta contained ribonuclease (RNase) activity which was demonstrable using yeast RNA or synthetic homopolymers of adenylic, cytidylic, inosinic, or uridylic acids as substrates. Polyguanylic acid was not hydrolyzed by worm RNase. RNase activity was inhibited by EDTA and divalent cations as well as sulfhydryl blocking and reducing agents. Polyguanylic acid and DNA were also inhibitors of RNase activity; these compounds were not hydrolyzed, but inhibited the hydrolysis of other substrates, possibly by nonproductive substrate binding. Data suggested that RNase (endonuclease) was probably the major enzyme activity in the degradation of long chain polyribonucleotides at the work's surface, while phosphodiesterase (exonuclease) activity did not contribute significantly to the hydrolysis of these compounds. PMID- 6267243 TI - Trypsin inactivation by intact Hymenolepis diminuta (Cestoda): some characteristics of the inactivated enzyme. AB - In the presence of intact Hymenolepis diminuta, trypsin was inactivated; intact worms had no apparent effect on subtilisin, pepsin, or papain. Inactivation of trypsin was demonstrable using azoalbumin as a substrate, but the inactivated enzyme retained full catalytic activity against benzoyl-DL-arginine-p nitroanilide, p-tosyl-L-arginine methyl ester (low molecular weight synthetic trypsin substrates) and p-nitro-p-guanidinobenzoate (an active site titrant). Inactivation was not reversible under conditions of heating, freezing and thawing, or prolonged dialysis of the enzyme. Analyses of inactivated 3H-trypsin by cationic and SDS-polyacrylamide gel electrophoresis, and gel chromatography failed to indicate the presence of a high molecular weight trypsin inhibitor associated with the inactivated enzyme; no low molecular weight, dissociable inhibitor was demonstrable following thermal denaturation of the inactivated enzyme. Analyses of trypsin after incubation in the presence of pulse-labeled worms also failed to demonstrate the presence of any inhibitor of worm origin associated with the inactivated enzyme. The data suggest that inactivation is the result of a small structural or conformational change in the enzyme molecule, a change which partially (rather than totally) inactivates the enzyme towards protein substrates. PMID- 6267244 TI - Antibodies to herpes simplex virus in human gingival fluid. AB - Antibodies to herpes simplex virus were found by immunofluorescent techniques in the gingival fluid of 84.0% of the persons tested. A mixture of IgG and IgA antibodies was demonstrated in 52.3% of the specimens while in 47.7% only IgG antibodies were found. Neutralization of herpes simplex virus infection in Vero cells by the gingival fluid was also demonstrated. No correlation between recurrences of herpes infection and the type of antibodies produced could be established. PMID- 6267245 TI - Antiparasitic structure-activity relationships of congocidine derivatives. AB - Several congocidine analogs were synthesized and tested for in vivo activity against Trypanosoma congolense and in vitro activity against amastigotes of Leishmania tropica. The tripyrrole derivative, beta-([N-methyl-4-[N-methyl-4 (guanidinoacetamido)pyrrole-2-carboxamido]pyrrole -2-carboxamido]pyrrole-2 carboxamido)butyroamidine dihydrochloride, was less toxic and more active than congocidine. The guanidinoacetyl moiety appears to be a structural requirement for antiparasitic activity in the congocidine series. PMID- 6267246 TI - The inhibitory effect of propranolol pretreatment on its own metabolism in the rat. AB - Repetitive oral administration of propranolol to rats (100 mg/kg/day for 5 days) resulted in a marked inhibition of hepatic microsomal metabolism of propranolol when incubated at low initial substrate concentrations (less than 2 microM). Associated with the inhibition of propranolol metabolism was a significant reduction in metabolites derived from naphthalene ring oxidation and an increased formation of N-desisopropylpropranolol. In vivo studies after propranolol pretreatment resulted in: an increased hepatic concentration and an increased systemic availability of propranolol; a decreased hepatic and plasma concentration of polar metabolites; and an increased plasma concentration of metabolites derived from propranolol N-dealkylation. Propranolol was converted both in vitro and in vivo by a hepatic microsomal mixed-function oxidase to a reactive metabolite capable of covalently binding with microsomal macromolecules. We propose that selective covalent binding of the reactive intermediate to the molecular form of cytochrome P-450 that ring hydroxylates propranolol would account for the marked inhibition of propranolol metabolism in vitro and for the increased systemic availability of propranolol in vivo after pretreatment. PMID- 6267247 TI - Cholinergic and alpha adrenergic augmentation of histamine-induced contraction of canine airway smooth muscle. AB - The effect of i.v. methacholine (MC) and norepinephrine (NE) in causing synergistic contraction of airways with histamine was studied in 31 anesthetized dogs. Dose-response studies were performed for individual agonists and then with agonists administered together for the same animal. The additive airway contractile response to i.v. MC and histamine and i.v. NE and histamine was less than that obtained for the same doses of these agonists administered by i.v. injection together in the same syringe. Synergism was observed for 0.005 microgram/kg to 5.0 microgram/kg i.v. of MC and 0.0025 microgram/kg i.v. of histamine, as measured by change in dynamic compliance (P less than 0.1), airway resistance (P less than .001), isometric tracheal smooth muscle tension (P less than .01) and duration of the tracheal contractile response (P less than 0.005). Synergism was also observed for 0.002 microgram/kg to 2.0 microgram/kg of NE and 0.0025 microgram/kg to 2.5 microgram/kg of histamine i.v. for airway resistance and dynamic compliance (P less than .025), isometric tracheal contraction (P less than .05) and duration of tracheal contraction (P less than .01). No augmentation was observed for seven animals receiving NE and MC at any dose nor was the duration of tracheal contraction to these combined agonists greater than additive. The addition of histamine to cholinergic or alpha adrenergic stimulation results in synergistic contraction of airways and augmentation of the duration of contractile response. This effect is specific for histamine, since no augmentation is seen when MC and NE are administered together. PMID- 6267248 TI - Reductions in retinal gamma-aminobutyric acid (GABA) content and in [3H]flunitrazepam binding after postnatal monosodium glutamate injections in rats. AB - Specific binding of [3H]flunitrazepam is found in the mammalian retina and its characteristics are similar in important respects to those in the cerebral cortex. Numerous reports have shown that monosodium glutamate (MSG) given neonatally to rats results in neuronal cell death with sparing of photoreceptor and glial cells. Sprague-Dawley rats were given MSG (3.2 mg/g i.p.) from day 2 to day 12 after birth; controls received equimolar injections of NaCl. At 8 to 9 weeks of age, the rats were killed and [3H]flunitrazepam binding was examined in the retinas are various brain regions. Histologic evidence showed the virtual absence of ganglion cells and a marked reduction of neurons in the inner nuclear layer of retinas from MSG-treated rats; photoreceptor and Muller cells appeared normal. In the retinas from MSG-treated rats, gamma-aminobutyric acid levels were decreased by 73% and the Bmax of [3H]flunitrazepam binding was decreased by 77%; there was no change in Kd. In the cerebellum, cerebral cortex and hypothalamus of MSG-treated rats, [3H]flunitrazepam binding was unchanged. These results strengthen the association of gamma-aminobutyric acid mechanisms with benzodiazepine binding and suggest a predominant neuronal localization of the binding sites. PMID- 6267249 TI - Benzodiazepine receptors are coupled to a subpopulation of gamma-aminobutyric acid (GABA) receptors: evidence from a quantitative autoradiographic study. AB - The colocalization and interaction of gamma-aminobutyric acid (GABA) and benzodiazepine (BZ) receptors in the rat brain were characterized using standardized, quantitative, light microscopic autoradiographic methods. In serial sections, striking differences were observed in the distribution of high affinity GABA and BZ receptors in areas such as the cerebral cortex, globus pallidus, thalamus, hypothalamus and cerebellar cortex. However, in a semiquantitative visual examination of more than 200 brain regions, added exogenous GABA increased BZ binding in all regions. In a quantitative analysis of 19 regions, exogenous GABA uniformly stimulated [3H]flunitrazepam binding, the effect being proportional to the regional density of BZ receptors. No relationship was seen between the magnitude of the stimulation and the distribution of high affinity GABA receptors. In the mounted tissue sections, BZ binding appeared influenced by endogenous GABA since it was reduced by preincubation or by the addition of bicuculline. Taken together, these data suggest that most or all BZ receptors can be influenced by GABA and are coupled to a type of GABA receptor. However, the BZ linked GABA receptor could represent either a subpopulation of GABA binding sites or a distinct receptor not labeled under the conditions used in these and other experiments. PMID- 6267250 TI - Transformation of signals by interneurones in the barnacle's visual pathway. AB - 1. The photoreceptors of the median eye of the giant barnacle drive decrementally conducting neurones in the supraoesophageal ganglion termed ;inverting cells' (I cells) which in turn drive impulse-producing neurones termed ;amplifying cells' (A-cells). Using intracellular recording techniques we have studied the role of I cells in visual processing.2. Horseradish peroxidase injections show that I-cells are interneurones whose processes are confined to the regions of the photoreceptor terminals on both sides of the bilaterally symmetrical ganglion.3. In the dark, I-cell membrane potentials (-45 mV) are considerably less negative than those of other ganglion cells (-60 to -70 mV). At the onset of a maintained light, I-cells undergo a transient peak hyperpolarization which declines to a steady-state response. Both response components are graded with light intensity.4. The reversal potential of the peak of the I-cell light response depends on the external K(+) concentration more strongly than does the dark resting potential (3-30 mm-K(+)). This evidence indicates that the hyperpolarization results from an increase in the cell's permeability to K(+) ions.5. At the offset of light an I-cell undergoes a transient depolarization that overshoots the dark membrane potential. Dimming of a background light can also cause the I-cell membrane potential to overshoot its dark resting value. This overshoot is associated with a large depolarizing synaptic potential in A cells.6. An overshoot of the dark resting potential can also be elicited by the break of a hyperpolarizing pulse of current injected into an I-cell. The amplitude of this overshoot increases with pulse duration over a time course of seconds.7. In the presence of external tetraethylammonium ion (TEA) and tetrodotoxin, (TTX), the break of a hyperpolarizing pulse or the onset of a depolarizing pulse can evoke in an I-cell an action potential whose rate of rise and amplitude depend on the external Ca concentration. This action potential can be maintained by replacement of external Ca with Ba, or blocked by addition of 15 mm-Co to the saline. These observation's indicate that depolarizing potential changes in this cell activate a voltage-sensitive Ca conductance.8. When hyperpolarizing current pulses are injected into an I-cell, the voltage during the pulse sags back slowly towards the dark resting potential. Thus, during hyperpolarization with light or current an I-cell's membrane properties change over a time course of seconds.9. The onset of a depolarizing pulse or the offset of a hyperpolarizing pulse of current injected into an I-cell leads to a transient depolarization of a simultaneously impaled A-cell. Synaptic transmission occurs when the I-cell is depolarized to the vicinity of the dark resting potential. The amplitude of the response in an A-cell depends on the rate of change of the I-cell voltage. PMID- 6267251 TI - The characteristics of synaptic currents and responses to acetylcholine of rat submandibular ganglion cells. AB - 1. Synaptic currents and responses to acetylcholine (ACh) have been recorded at 20 degrees C from rat submandibular ganglion cells by a two micro-electrode volatage-clamp technique.2. The peak amplitude (a(p)) of excitatory synaptic currents (e.s.c.s) was linearly related to membrane potential (E(m)), with a reversal potential close to - 10 mV. E.s.c.s decayed with a bi-exponential time course, the fast phase comprising just over half the total amplitude. The time constant (tau(f)) of the fast phase was 5-9 msec, while that of the slow phase (tau(s)) was 27-45 msec. The relative amplitudes of the two components remained constant at different membrane potentials, showing that the reversal potential was the same for both.3. Both tau(f) and tau(s) increased as the cell was hyperpolarized, the ratio tau(-80)/tau(-40) being about 1.6 for both fast and slow components.4. Increasing the calcium concentration from 2.5 to 7.5 mm increased the amplitude of both components by about 40% and also prolonged the synaptic currents 30-50%, its effect being slightly greater on tau(s) than on tau(f).5. In contrast to e.s.c.s, spontaneous or potassium-evoked miniature synaptic currents (m.s.c.s) showed a simple exponential decay with a time constant (tau(m.s.c.)) very similar to tau(f). tau(m.s.c.) showed the same sensitivity to membrane potential and calcium concentration as tau(f).6. In the presence of neostigmine (10 mum) e.s.c.s were prolonged, tau(f) about 3.5-fold and tau(s) about 2.5-fold. The decay remained bi-exponential, with little change in the relative amplitude or voltage-dependence of the two components. M.s.c.s were prolonged to a lesser extent (1.5-2-fold) and the voltage dependence of tau(m.s.c.) was unaffected by neostigmine.7. Reduction of the quantal content of the e.s.c. by low calcium-high magnesium solution did not affect the time course. The relative amplitudes, and the time constants of the two components were unchanged even with a 90% reduction of a(p).8. Voltage-jump studies, in which the cell was abruptly hyperpolarized by 20-40 mV during a response to ionophoretically applied ACh, showed a relaxation pattern consisting of two distinct exponential components, whose relative amplitudes varied considerably in different cells. The two rate constants tau(f.rel) and tau(s.rel) were somewhat shorter than tau(f) and tau(s) for e.s.c.s, the difference being generally less than two-fold.9. Measurements of ACh noise also revealed two kinetic components, the time constants of which corresponded closely to tau(f) and tau(s) for e.s.c.s. On the assumption that the two components represent channels of equal conductance, the single channel conductance, gamma, was calculated to be 31+/-3 pS, similar to that of endplate channels.10. It is concluded that the two kinetic components of e.s.c.s and ACh responses probably represent two distinct classes of ACh-operated ionic channels, whose mean lifetime differs about fivefold. The two types of channel show the same ionic selectivity and their mean lifetime varies in the same way with the membrane potential. The absence of a slow component in m.s.c.s suggests that the two types of channel are spatially separate in the membrane. PMID- 6267252 TI - Properties of end-plate channels in rats immunized against acetylcholine receptors. AB - 1. Rats injected with purified acetylcholine receptors (AChR) extracted from electric organs of Torpedo marmorata showed clinical symptoms consistent with the development of experimental myasthenia gravis.2. Sera of rats with this disease contain high levels of anti-AChR antibodies. However, no simple correlation was found between antibody titre and miniature end-plate current (m.e.p.c.) amplitude.3. M.e.p.c.s. at the end-plates of rats injected with AChR (Anti-R), emulsified in complete Freund Adjuvant (CFA), were reduced to about one third the size of controls taken from rats injected only with CFA (Anti-CFA). Mean m.e.p.c. (Anti-R) = 0.73 +/- 0.06 nA; mean m.e.p.c. (Anti-CFA) = 2.43 +/- 0.12 nA (V(m) = 80 mV, T = 20 degrees C).4. The m.e.p.c. decay time constant, tau(m.e.p.c.), is similar at immunized and control rat end-plates. tau(m.e.p.c.) (Anti-R) = 1.32 +/ 0.06 msec; tau(m.e.p.c.) (Anti-CFA) = 1.31 +/- 0.06 msec (V(m) = -80 mV, T = 20 degrees C).5. The end-plate current decay time constant, tau(e.p.c.), is similar at immunized and control end-plates and in both cases depends exponentially on membrane potential. The change in membrane potential required to produce an e fold change in tau(e.p.c.) is 102.0 +/- 5.72 mV at immunized (Anti-R) end-plates and 92.3 +/- 6.14 mV at control (Anti-CFA) end-plates at T = 10 degrees C.6. Acetylcholine noise was examined at immunized and control rat end-plates at 10 degrees C. Analysis of noise indicates that the single channel conductance, gamma, and mean channel life-time, tau(noise), are essentially unchanged by immunization against AChR. gamma (Anti-R) = 13.15 +/- 0.53 pS; gamma (Anti-CFA) = 12.50 +/- 0.50 pS; tau(noise) (Anti-R) = 2.9 +/- 0.18 msec; tau(noise) (Anti-CFA) = 2.68 +/- 0.14 msec (V(m) = -80 mV, T = 10 degrees C).7. Mean quantal content and Ca(2+) dependence of the end-plate potential are unchanged at immunized end plates.8. It is concluded that at immunized end-plates the number of activated receptor-channel complexes is reduced without modification of single channel properties. In this respect the immunized rat end-plate is a good model for myasthenia gravis affected human end-plates. PMID- 6267253 TI - Is the quantum of transmitter release composed of subunits? A critical analysis in the mouse and frog. AB - 1. Miniature end-plate potentials (m.e.p.p.s) were recorded from mouse diaphragm and frog cutaneous pectoris muscles and miniature end-plate currents (m.e.p.c.s) were recorded from frog cutaneous pectoris to investigate the proposal that the m.e.p.p. is built up of one to thirty subunits. Evidence for this hypothesis is drawn mainly from the observations that there is a class of m.e.p.p.s smaller than the classical m.e.p.p.s, and that histograms of m.e.p.p. amplitudes display multiple peaks which often appear to be regularly spaced and which extend throughout the histograms; in terms of the subunit hypothesis each successive peak results from an increasing integral number of subunits per m.e.p.p. (Kriebel, Llados & Matteson, 1976; Wernig & Stirner, 1977).2. Histograms of m.e.p.p. amplitudes and m.e.p.c. areas confirmed the existence of two classes of m.e.p.p.s as reported by Kriebel & Gross (1974): a larger class (well described by a Gaussian curve) which consists of the classical m.e.p.p.s, and a smaller class with amplitudes considerable less than the classical m.e.p.p.s.3. Histograms of m.e.p.p. amplitudes and m.e.p.c. areas showed multiple peaks that extended throughout the histograms.4. Autocorrelations of the histograms, an unbiased method used to test for regularity in data, showed that the multiple peaks were not regularly spaced, as required by the subunit hypothesis.5. A series of computer simulations demonstrated that, for expected levels of base line noise in the recording system, multiple peaks that extend throughout histograms of m.e.p.p. amplitudes could arise from subunits only if the standard deviation of the subunit amplitude were less than 2-5% of the mean subunit amplitude and the standard deviation of the variability in post-synaptic sensitivity were less than 2% of the mean post-synaptic sensitivity. It seems unlikely that the variability in post-synaptic sensitivity and in proposed subunit amplitude would be as small as this.6. Taking more realistic estimates for the standard deviation of the subunit amplitude of 12% of the mean subunit amplitude and standard deviation of the variation in post-synaptic sensitivity of 4% of the mean sensitivity, it was found that at most three to four regularly spaced peaks would be apparent in m.e.p.p. amplitude histograms due to subunits.7. On the basis of these theoretical considerations it seems doubtful that the multiple peaks observed to extend throughout histograms of m.e.p.p. amplitudes could arise from subunits; therefore, the experimental data that have been used to support the subunit hypothesis are unlikely to have arisen from a subunit mechanism.8. We suggest that there are few, if any, data that directly support the subunit hypothesis. The multiple peaks observed to extend throughout m.e.p.p. amplitude histograms most likely arise from random variation in the data, although additional factors cannot be ruled out. PMID- 6267254 TI - Unitary current through sodium channel and anomalous rectifier channel estimated from transient current noise in the tunicate egg. AB - 1. The noise included in the Na current and the anomalous rectifier current was measured in intracellularly perfused eggs of Halocynthia roretzi Drashe under voltage clamp conditions. 2. The time-dependent component of the point-by-point ratio between the ensemble mean and the variance of successive current traces was the mirror image of the time-dependent component of the mean current itself. This can be explained by assuming an open or closed conductance state for each ionic channel, and permits estimation of unitary currents and channel number. 3. The unitary Na currents showed a potential dependence similar to that of the instantaneous currents. The unitary conductances (gamma) at zero membrane potential were 7.4 and 3.3 pmho in sea water with 400 and 100 mM-Na, respectively, and 400 mM-intracellular K. With 400 mM-Na intracellular perfusate and 400 mM-Na sea water, gamma was 15.7 pmho. In spite of the large differences in the unitary conductances, the single channel permeability for Na ions remained constant (1.15 x 10(-14) cm3 sec-1). The density of Na channels was 0.60/micrometer2. 4. The unitary currents calculated for the anomalous rectifier showed a potential dependence similar to that of the zero-time extrapolated estimates of the K inward currents. The anomalous rectifier unitary conductance was 5.5 and 6.9 pmho for sea water with 50 and 100 mM-K, respectively. The density of these channels was 0-035/micrometer2. PMID- 6267255 TI - Non-linear summation of end-plate potentials in the frog and mouse. AB - 1. End-plate potentials (e.p.p.s) and end-plate currents (e.p.c.s) were recorded intracellularly from muscle fibres of frog and mouse at various levels of curarization to determine the relation between the potential change and the underlying synaptic conductance change over a wide range of e.p.p. amplitudes. 2. In frog muscle fibres the e.p.p.-e.p.c. relation was linear for e.p.p. amplitudes up to about 10 mV, beyond which the rate of increase of e.p.p. amplitude became progressively smaller as the e.p.c. amplitude increased. The equation proposed by Martin (1955) to correct for this non-linearity consistently over-corrected the e.p.p. amplitudes. 3. When synaptic potentials and currents of long duration were produced by ionophoresis of ACh onto the end-plate, the voltage-current relation showed greater non-linearity than with nerve-evoked responses, and correction of the synaptic potential amplitudes resulted in a linear relation. 4. The relation between e.p.p. and e.p.c. amplitudes in mouse muscle showed a greater non linearity than in frog muscle and over-correction by the equation was correspondingly smaller. Theoretical voltage-current relations were calculated for various membrane models and compared with the relations observed experimentally. The results from mouse muscle agreed with those expected for a point synaptic contact on an infinite cable; those from from muscle were consistent with simple resistive-capacitative model with no cable extending from the synaptic region. 6. The applicability to the experimental results of several correction factors for non-linear summation is discussed. PMID- 6267256 TI - Comparison of enzyme activities among single muscle fibres within defined motor units. AB - 1. Muscle fibres from single motor units of rat extensor digitorum longus were depleted of their glycogen by electrical stimulation and identified by the periodic acid-Schiff stain after treatment in a medium that selectively enhanced glycogen content in the non-depleted fibres. 2. Malate dehydrogenase (MDH) and fructose-1,6-diphosphatase (FDPase) activities were studied quantitatively in single dissected fibres of individual motor units and in fibres selected randomly from the same muscle. 3. In contrast to the large variability of MDH and FDPase in muscle fibres taken randomly, the muscle fibres from the same motor units had similar enzyme activities. 4. The resistance to fatigue of the motor units correlated well with the capacity of aerobic oxidative metabolism, as judged by the activity of MDH in the muscle fibres. PMID- 6267257 TI - Transmission at a 'direct' electrical connexion mediated by an interneurone in the leech. AB - 1. Touch sensory neurones in the leech excite a rapidly conducting interneurone called the S-cell. Although the electrical synaptic connexion between the two cells is monosynaptic by physiological criteria, intracellular staining reveals that the touch cells and the S-cell do not make contact, but instead are linked by a pair of small interneurones. 2. The electrical coupling between touch cells and S-cells rectifies, in that depolarizing current but not hyperpolarizing current passes from the touch cell into the S-cell. The rectifying junction is between the touch cells and coupling interneurones, while the connexion between coupling interneurones and the S-cell passes current in both directions. 3. Selective destruction of the coupling interneurones by intracellular injection of a protease interrupts the disynaptic electrical connexion between touch and S cells. 4. The touch cell's geometry and membrane properties account for the failure of impulses that are generated in certain portions of the receptive field in the skin to propagate beyond the first branch-points of the touch cell axon within the ganglion. Conduction block at branch-points is used to examine physiologically the spatial distribution of contacts between the touch cell and the coupling interneurones. In addition, it is shown that under natural conditions branch-point failure presynaptically reduces the effectiveness of the electrical synaptic connexions. PMID- 6267258 TI - The effect of profound cooling on adrenergic neurotransmission in canine cutaneous veins. AB - 1. Experiments were performed to investigate how profound cooling affects adrenergic neurotransmission and vascular smooth muscle reactivity in isolated saphenous veins of the dog. 2. Cooling from 37 to 5 degrees C caused progressive depression of the contractile responses to high K+ solutions, illustrating the direct inhibitory effect of cooling on depolarization-induced contraction of the venous smooth muscle cells. 3. During prolonged cooling to 20, 15 and 10 degrees C, the contractile response to exogenous norepinephrine (10(-8)-10(-6) M) was augmented compared to that at 37 degrees C. At 5 degrees C responses up to 10(-7) M were also augmented, but those at higher concentrations were depressed. When veins contracted with 2 x 10(-6) M-norepinephrine were cooled to 20, 15, 10 and 5 degrees C, there was a further increase in tension; this increase slowly subsided to control values at 5 degrees C but was sustained at the other temperatures. 4. Cooling to 20 and 15 degrees C augmented the contraction caused by low but not high frequencies of electrical stimulation of the adrenergic nerve endings. Further cooling to 10 degrees C depressed, and at 5 degrees C abolished the response, demonstrating that profound cooling interrupted adrenergic neurotransmission. 5. In rings stimulated electrically at a low frequency (0.5 Hz), warming from 7 to 9 degrees C or from 9 to 11 degrees C, caused marked increases in tension. This may be explained by the combination of resumption of adrenergic neurotransmission and the increased responsiveness of the cutaneous venous smooth muscle cells to adrenaline. 6. The combination of enhanced affinity for noradrenaline combined with inhibition of neurotransmitter disposition probably permits the cutaneous veins to remain constricted during exposure to severe cold. PMID- 6267259 TI - The inotropic actions of adrenaline on frog ventricular muscle: relaxing versus potentiating effects. AB - 1. In frog ventricle, adrenaline increases the size of the action potential, potentiates twitch tension, and enhances relaxation. Because tension development is directly controlled by membrane potential in frog ventricle, experiments were designed to separate the effects of adrenaline on the action potential from its effects on the development of tension.2. Comparison of the tension-voltage relations in the presence and absence of adrenaline showed that during the initial portion of the voltage clamp step, adrenaline potentiated tension, but beyond 1 sec into the clamp pulse tension was depressed.3. The time and voltage dependence of the positive inotropic effect of adrenaline during voltage clamp pulses were compatible with the kinetics of the slow inward current, which is known to be augmented by adrenaline in frog and mammalian ventricle.4. Ni(2+), which has been shown to block the slow inward current in frog ventricle, also inhibited the positive inotropic effect of adrenaline.5. The relaxant effect of adrenaline was demonstrated to be present at least as early as 600 msec after the onset of membrane depolarization. However, generally 1 sec or more of membrane depolarization was required before the relaxant effect of adrenaline predominated over its positive inotropic effect.6. In catecholamine depleted strips, the augmentation of the action potential and twitch tension in the presence of adrenaline was found to occur at a sixty-fold lower concentration than the relaxant effect as judged by suppression of KCl-induced contractures.7. Pure beta receptor agonists reproduced completely the electromechanical effects of adrenaline on the frog ventricle. alpha-receptor agonists or antagonists had no effect on action potential or development of tension.8. Cyclic AMP and dibutyryl cyclic AMP were found to augment the frog ventricular action potential and potentiate twitch tension in reserpinized or beta-blocked frog ventricular strips. However, none of the relaxant effects of catecholamines could be reproduced by these agents alone.9. Theophylline produced changes in the action potential similar to those induced by adrenaline and mimicked both the positive inotropic and relaxant effects of the drug.10. The results suggest that the positive inotropic effects of adrenaline results mainly from changes induced in the action potential plateau. The changes are both time and voltage dependent, and if inhibited, leave the relaxant effect of adrenaline unopposed.11. The findings are consistent with a cyclic AMP-mediated mechanism of the positive inotropic effect of adrenaline. However, the role of cyclic AMP in mediating the relaxant effects of adrenaline is less clear. PMID- 6267260 TI - The influence of concanavalin A on glutamate-induced current fluctuations in locust muscle fibres. AB - 1. The influence of the plant lectin Concanavalin A (ConA) on the properties of membrane channels opened by 25-200 microM-L-glutamate in voltage-clamped locust muscle fibres has been studied. Power spectral density plots of membrane current fluctuations were used to estimate the mean lifetime and conductance of glutamate induced channels. 2. Exposure to ConA (10 micrograms/ml.) increased the amplitude of the mean current evoked by 200 microM-glutamate from 7.7 +/- 4.7 nA (mean +/- S.D.) to 81 +/- 57 nA (membrane potential -60 mV, temperature 16 degrees C). The mean conductance of glutamate-induced channels (65 +/- 16.8 pS at 16 degrees C) was negligibly affected by the lectin. 3. In normal saline the mean lifetime of glutamate-induced channels tau noise decreased on membrane hyperpolarization. After treatment with ConA (70 micrograms/ml.), tau noise become totally independent of membrane voltage when studied at potentials in the range -60 to 120 mV. The value of tau noise at the resting potential was little altered by the lectin. PMID- 6267261 TI - Slow calcium and potassium currents across frog muscle membrane: measurements with a vaseline-gap technique. AB - 1. A vaseline-gap voltage-clamp technique was used to record slow Ca2+ and K+ currents from frog skeletal muscle fibres loaded with the Ca2+ chelator EGTA. 2. K+ currents were increased when Mg2+ replaced external Ca2+, and they were abolished when internal K+ was replaced by tetraethylammonium (TEA+). Ca2+ currents could be studied in isolation in fibres loaded with (TEA)2EGTA. 3. Under maintained depolarization, Ca2+ currents slowly increase (half-time of 35 msec or more at 25 mV) and then decline to a steady value. Decline under repolarization is rapid (half-time of 6-7 msec) and complete. During an action potential, the Ca2+ influx through this system is probably less than the influx observed with tracers. 4. Ba2+, Sr2+, Ca2+, Mn2+ and Mg2+ can carry current across the membrane; Ni2+ and Co2+ cannot. Ca2+ currents are weakly blocked by external Mg2+. PMID- 6267262 TI - Calcium depletion in frog muscle tubules: the decline of calcium current under maintained depolarization. AB - 1. Ca2+ currents in frog skeletal muscle fibres were studied with a voltage-clamp technique. Under membrane depolarization maintained for several seconds, Ca2+ current was found to decline with time constants of 0.2-2 sec when [Ca2+]o = 10 mM. 2. Ca2+ currents are diminished by nifedipine, D-600, tetracaine and Ni2+. 3. When peak current is diminished by making the membrane potential positive, by block with drugs or by substituting the relatively less permeant Mn2+ for Ca2+ then the rate of decline is diminished also. When peak current is increased by recording at relatively negative membrane potentials or by substituting for Ca2+ the more permeant ions Ba2+ or Sr2+, then the rate of decline is increased in proportion. Evidently, the size of the current determines the rate of decline. 4. Decline of current is greatly slowed in isotonic Ca2+ saline or when the [Ca2+]o is buffered by the organic anion malate. These findings indicate that the decline of current arises from Ca2+ depletion in an extracellular compartment, most probably the transverse tubules. On this basis, an analysis of Ca2+ current decline and recovery leads to the following conclusions. 5. Ca2+ current flows almost entirely across the membranes of the transverse tubules. 6. After allowing for the tortuosity of the tubular network, the apparent diffusion coefficient for Ca2+ in the transverse tubules is about 2.6 X 10(-6) cm2/sec, three times less than the diffusion coefficient for K+ in the transverse tubules and about three times less than the diffusion coefficient for Ca2+ in free solution. 7. The transverse tubule lumen does not appear to have a large Ca2+-buffering capacity in the millimolar range. At [Ca2+]o = 10 mM, the tubule lumen binds less than 0.6 dissociable Ca2+ ions for every free ion. PMID- 6267263 TI - Channel gating at frog neuromuscular junctions formed by different cholinergic neurones. AB - 1. Drug-induced membrane current fluctuations were analysed at frog ectopic neuromuscular junctions formed de novo by somatic motoneurones and by preganglionic autonomic neurones of the vagus nerve, and at denervated end-plates reinnervated by the vagus nerve. 2. At ectopic motor end-plates, the mean open time of the ion channels activated by ACh is tau ACh = 1.8 +/- 0.1 msec (S.E.) at -70 to -90 mV and 15-18 degrees C. Carbachol- and suberyldicholine-induced channels have average open times tau Carb = 1.0 +/- 0.1 msec (-80 mV, 6-8 degrees C) and tau Sub = 3.3 +/- 0.1 msec (-80 mV, 16-18 degrees C). 3. The conductances gamma of single channels induced by ACh, carbachol and suberyldicholine are: gamma ACh = 21.0 +/- 1.1 pS (+/- S.E.), gamma Carb = 14.6 +/- 1.2 pS and gamma Sub = 22.1 +/- 1.2 pS. 4. The mean open times tau of the channels is prolonged as the membrane is hyperpolarized. Their voltage dependence is similar to that of normal end-plate channels. 5. The average open time of ACh-induced channels at ectopic vagus junctions is tau = 1.6 +/- 0.2 msec (S.E.) at -70 to -80 mV and 14 15 degrees C. At denervated motor end-plates reinnervated by vagal neurones, the mean channel open time is tau = 1.5 +/- 0.1 msec at -80 mV and 14-18 degrees C. 6. At all vagus junctions, the synaptic currents are blocked by alpha bungarotoxin. 7. Somatic motoneurons and vagal neurones induce junctional folds in the muscle membrane where they contact it to form an ectopic end-plate. Staining the ACh receptors of the motor end-plates with horseradish peroxidase alpha-bungarotoxin conjugate shows that the receptors are restricted to the junctional region of the muscle fibre membrane. PMID- 6267265 TI - Analysis of subthreshold pace-maker currents in chick embryonic heart cells. AB - 1. Small re-aggregates of cells dissociated from the ventricles of 7-day-old chick embryonic hearts beat spontaneously in low external potassium concentration (Ko = 1.3 mM) tissue culture medium. This activity was blocked by the addition of tetrodotoxin (TTX) or potassium ions to the external medium. 2. A two-micro electrode voltage-clamp technique was used to analyse the subthreshold currents responsible for the pace-maker depolarization. 3. Voltage-clamp steps 6-10 sec in duration revealed a time-dependent current having first order kinetics. Its membrane potential range of steady-state activation was -90 to -60 mV. 4. The current kinetics were qualitatively similar to those of Hodgkin & Huxley (1952b) with a peak time constant of approximately 1 sec at V = -75 mV. The kinetics were independent of Ko. 5. The time-dependent current was attributed to gated membrane channels. The fully activated current-voltage (I-V) relation of the channels was determined from the ratio of the amplitudes of the time-dependent currents during and after voltage-clamp steps following the procedure of Noble & Tsien (1968). 6. The fully activated I-V relation displayed inward rectification with negative slope conductance at potentials more than 15 mV positive to its reversal potential. Changes of Ko shifted the I-V curve along the voltage axis like a potassium electrode. 7. The time-independent (background) current was obtained by subtracting the gated channel current from the steady-state I-V curve. This current also rectified in the inward direction. 8. The inwardly rectifying I-V relations were theoretically described by a channel having a row of ion-selective sites along which ions move in a single file (Hodgkin & Keynes, 1955), and a membrane-bound particle which blocked the channel in a voltage-dependent manner. 9. The relationship of the voltage-clamp results to spontaneous activity is discussed and comparisons are made with measurements from whole embryonic heart and other cardiac tissues. PMID- 6267264 TI - Site(s) and ionic basis of alpha-autoinhibition and facilitation of "3H'noradrenaline secretion in guinea-pig vas deferens. AB - 1. Mechanisms controlling the secretion of [(3)H]noradrenaline from the noradrenergic nerves of guinea-pig isolated vas deferens, prelabelled by incubation with [(3)H]noradrenaline, were studied using (a) different modes of (extramural or transmural) electrical nerve stimulation (a total of 300 shocks of varying strength, and a duration of 2 msec) at 1-30 Hz, or (b) depolarizing concentrations of K(+) (60-110 mm).2. The fractional rise in efflux of (3)H labelled material (Deltat) was used to measure the secretion of [(3)H]noradrenaline.3. The dependence of [(3)H]noradrenaline secretion on the external Ca(2+) concentration (1-8 mm) was essentially hyperbolic. Double reciprocal plot analysis (1/Deltat vs. 1/Ca(2+)) of the data yields that blockade of alpha-autoinhibition (phentolamine 1 mum) does not increase the maximal secretory velocity, but does enhance the apparent affinity of the secretory mechanism for external Ca(2+). Exogenous noradrenaline has (qualitatively) opposite effects. The interaction between alpha-autoinhibition and external Ca(2+) thus shows a ;competitive' pattern, indicating that restriction of the utilization of external Ca(2+) is a major mechanism in alpha-autoinhibition of noradrenaline secretion, in this system.4. Phenoxybenzamine (10 mum) and phentolamine (1 mum) increased the secretion of [(3)H]noradrenaline evoked by depolarization with K(+) much less than that caused by electrical nerve stimulation (frequencies up to 10 Hz). Exogenous noradrenaline (1-5 mum) depressed the secretion evoked by both modes of stimulation. The results indicate that alpha-autoinhibition of [(3)H]noradrenaline secretion is mainly operative when the secretory stimulus requires conduction of nerve impulses between varicosities.5. The frequency dependence of [(3)H]noradrenaline secretion was hyperbolic, both in the presence and in the absence of alpha-autoinhibition; at each frequency the secretion (Deltat per shock) increased with the Ca(2+) concentration in the medium (0.6-8 mm). Double reciprocal plot analysis (1/Deltat vs. 1/frequency) of the data yields that the pattern of interaction between external Ca(2+) and facilitation depends on the presence or absence of alpha autoinhibition (phentolamine 1 mum); in the former case it is ;non-competitive', in the latter ;competitive'. Similar analysis of the effect of facilitation by increasing the length of stimulus trains (from 5 to 300 pulses) at a constant frequency (5 Hz), on the Ca(2+) dependence of Deltat (1/Deltat vs. 1/Ca(2+)) in the absence of alpha-autoinhibition also yields that facilitation promotes utilization of external Ca(2+). These results apparently imply that a rise in external Ca(2+), in the presence of alpha-autoinhibition, augments the secretory response to electrical nerve stimulation mainly by promoting recruitment of active units (varicosities?), without markedly altering their ;affinity' for facilitation. In the absence of autoinhibition (when all units are already recruited?), the results seem to imply that facilitation promotes depolarization secretion coupling in each, by more efficient utilization of external Ca(2+).6. The pattern of interaction between alpha-autoinhibition and facilitation depends on the Ca(2+)concentration in the medium. At or below the physiological level of Ca(2+) in extracellular fluid (1.2 mm) it is ;non-competitive', indicating that alpha-autoinhibition and facilitation act, at least in part, at separate targets under these conditions. At high (5.4 mm) external Ca(2+) the pattern becomes almost purely ;competitive', indicating that facilitation can, under suitable conditions, overcome all manifestations of alpha-autoinhibition.7. The secretion evoked by electrical nerve stimulation (Deltat per shock, at 1 or 10 Hz) increased with the strength of applied shocks, both when applied extra- or transmurally, in the presence or absence of alpha-autoinhibition. In the former case the rise in (Deltat per shock) vs. (current strength) was hyperbolic, in the latter it followed a biphasic pattern. Double reciprocal plot analysis (1/Deltat vs. 1/current) of the data yields a ;non-competitive' pattern of interaction between facilitation or alpha-autoinhibition, and exogenous current, when stimulation was extramural. When it was transmural the pattern is ;competitive'. The results seem to imply that hyperpolarization, or depolarization, of nerve terminals are major mechanisms whereby alpha-autoinhibition and facilitation, respectively, exert their effects on the secretory response to electrical nerve stimulation.8. Neither activation of Na(+), K(+)-ATPase, nor promotion of G(Cl) appear to be critically involved in alpha-autoinhibition. Experiments with known blockers of G(K) (tetraethylammonium, 4-aminopyridine and Rb(+)) did not give support to the notion that promotion of K(+) efflux is a mechanism whereby prejunctional alpha-adrenoceptors cause (hyperpolarization of nerve terminals and) autoinhibition of secretion. If alpha-autoinhibition does involve K(+) channels in the nerve terminal membrane, then these must be different from the (voltage-sensitive) K(+) channels blocked by the above mentioned inhibitors of K(+) efflux.9. The results are discussed in the context of a model that assumes that local control of noradrenaline secretion from noradrenergic nerves may be exerted both by control of invasion of terminals, and by control of depolarization-secretion coupling in each invaded varicosity. Under suitable conditions facilitation and alpha-autoinhibition may interact at both levels. It proposed that utilization of external Ca(2+) plays a pivotal role for both, and that restriction of invasion of nerve terminal varicosities is the main effect of alpha-autoinhibition, while promotion of depolarization-secretion coupling is the main effect of facilitation, at physiological concentrations of Ca(2+) in the medium. For the nerve the role of this dual control system is proposed to be to ensure ;rotational' activation of varicosities, and for the effector cell of noradrenergic junctions, to increase the signal/noise ratio. PMID- 6267266 TI - Developmental changes in subthreshold pace-maker currents in chick embryonic heart cells. AB - 1. Small re-aggregates of cells dissociated from the ventricles of 12-or 17-day old chick embryonic hearts have beating properties in low potassium tissue culture medium which differ from re-aggregates prepared from 7-day-old hearts; 12 day preparations either beat with a slower rate than comparable-size 7-day preparations or they are quiescent; 17-day preparations usually do not beat. 2. A two-micro-electrode voltage-clamp technique was used to analyse the membrane currents in these preparations in the -120 to -40 mV potential range. 3. A potassium ion membrane current was measured in 12-day and 17-day preparations which was qualitatively similar to the potassium ion current measured in 7-day preparations (Clay & Shrier, 1981). It differed in that its amplitude was diminished in the ratio 1:0.2:0.03 over the 7-, 12- and 17-day sequence. Furthermore, its maximum time constant was 2 sec at both 12 and 17 days, as compared to 1 sec at 7 days, and its membrane potential range of activation was 80 to -70 mV at 12 and 17 days, as compared to -90 to -60 mV at 7 days. 4. The background current also changed with development, becoming less inward over the 7 , 12- and 17-day sequence. The voltage dependence of this change suggested that it was caused by a developmental decrease of the background sodium current. 5. The change in the background component is primarily responsible for the loss of automaticity over the 7-, 12-, and 17-day sequence. PMID- 6267267 TI - Sidedness of the effects of sodium and potassium ions on the conformational state of the sodium-potassium pump. AB - 1. (Na,K)ATPase from kidney membranes has been reconstituted into proteoliposomes following solubilization in cholate, by the freeze-thaw sonication procedure described by Kasahara & Hinkle (1977). The method is rapid and convenient.2. Upon addition of ATP to the exterior medium the reconstituted vesicles sustain high rates of active (22)Na uptake and (86)Rb efflux with many properties similar to those of the Na/K pump in well characterized cells such as erythrocytes.3. Observations on both active and passive transport of (22) Na and (86)Rb indicate that the vesicle population is heterogeneous; about 40 per cent contain Na/K pumps and the remainder seem to be plain lipid vesicles.4. The major Na(+)- or K(+)-stabilized non-phosphorylated conformational forms of the (Na, K)ATPase, E(1). Na and E(2). (K) respectively, have been investigated in the proteoliposomes, with particular regard to sidedness of the actions of Na(+) and K(+).5. Tryptic digestion of the vesicles reveals the Na(+)- and K(+)-stabilized conformations E(1). Na and E(2). (K) as characterized originally for purified (Na, K)ATPase (Jorgensen, 1975). Controlled trypsinolysis of Tris(+)-loaded vesicles in a Na(+)-or K(+)-containing medium leads to typical biphasic (Na(+)) or simple exponential (K(+)) time courses respectively, for loss of ATP-dependent (22)Na uptake (assayed subsequent to the tryptic digestion in the presence of inophores valinomycin plus FCCP). Tryptic digestion of K(+)- or Rb(+)- or Tris(+) loaded vesicles suspended in a Na(+) medium results only in the biphasic (E(1). Na) pattern of loss of ATP-dependent (22)Na uptake.6. ATP-dependent (22)Na uptake and (86)Rb efflux are reduced by about the same extent following a short tryptic digestion in a Na(+)-containing medium.7. Vanadate ions inhibit ATP-dependent (22)Na uptake into the vesicles, at low concentrations (K(0.5) approximately 2 x 10(-7)m), following pre-incubation together with Mg(2+) and K(+) ions. K(+) ions in the medium are effective, K(+) ions within the vesicle are not. Na(+) ions in the medium prevent inhibition by vanadate+Mg(2+) but do not reverse inhibition in vesicles pre-incubated with vanadate, Mg(2+) and K(+) ions.8. The results show that the conformational forms E(1). Na and E(2). (K) are stabilized by Na(+) or K(+) ions respectively, bound to sites on the Na/K pump normally facing the cytoplasm. The significance of this finding is discussed in relation to the cation transport function of the pump. PMID- 6267268 TI - Some effects of n-pentane on the sodium and potassium currents of the squid giant axon. AB - 1. Sodium and potassium currents have been recorded in intracellularly perfused squid giant axons before, during and after exposure to solutions of n-pentane in artificial sea water. 2. The currents were fitted with equations similar to those proposed by Hodgkin & Huxley (1952) and the changes in the parameters of these equations in the presence of pentane were calculated. 3. In the range of membrane potential -40 to 40 mV, the time constants for activation (tau m) and inactivation (tau h) of the Na current, and for activation (tau n) of the K current were all reduced by the pentane. 4. The curve of the steady-state inactivation parameter (h infinity) for the Na current against membrane potential was shifted by the pentane in a hyperpolarizing direction (at h infinity = 0.5 this shift was approx. -15 mV in 275 microM-pentane) and the slope at all potentials was reduced. 5. The curve of the steady-state activation parameter (m infinity) for the Na current against membrane potential was also shifted by the pentane in a hyperpolarizing direction (in 153 microM-pentane, 10 mV at m infinity = 0.5). 6. The maximum Na and K conductances gNa and gK were lowered by the pentane, though not usually completely reversibly. 7. The changes in position and slope of the steady-state inactivation curve have been tentatively accounted for in terms of an increase in membrane thickness. PMID- 6267270 TI - No-suicide contract for nurses. PMID- 6267269 TI - The effect of (+)-tubocurarine on neuromuscular transmission during repetitive stimulation in the rat, mouse, and frog. AB - 1. The effect of tubocurarine on amplitudes of end-plate currents in response to trains of repetitive stimulation (50-150/sec) was investigated in voltage-clamped muscle fibres of the rat, mouse and frog. 2. In rat and mouse muscle, the presence of tubocurarine led to a more rapid decline (rundown) in the amplitudes of successive end-plate currents during trains of impulses. In frog, tubocurarine caused an increase in apparent facilitation of end-plate current amplitudes during the first few impulses of repetitive stimulation; this increase was followed by a more rapid rundown of end-plate current amplitude. 3. These effects of tubocurarine appear not to be an artifact resulting from inadequate control of membrane potential in voltage-clamped fibres. 4. The more rapid rundown during trains of end-plate currents in the presence of tubocurarine showed little variation with membrane potential indicating that voltage-sensitive channel blockade by tubocurarine was not a major factor contributing to the rundown. 5. The effect of tubocurarine on the apparent facilitation and rundown of end-plate current amplitudes was typically decreased by reducing the frequency of stimulation. 6. These results suggest that tubocurarine affects transmitter release at neuromuscular junctions during repetitive stimulation. PMID- 6267271 TI - Structure for the hospitalized adolescent. PMID- 6267272 TI - Fatherhood and disturbances of mental health: a review. PMID- 6267273 TI - Preparation of psychiatric inpatients for group therapy. AB - Nurses have been acquiring the skills necessary for involvement as cotherapists in group therapy with increasing frequency and have been taking a more active role in the inpatient psychiatric treatment. Preparation of patients for group therapy is supported by the literature for outpatients and equivocally supported for inpatients by this study. Nurses, with their frequent and prolonged contact with inpatients, are in the unique position of being able to form a close, consistent relationship that allows them to assess expectations, plan individualized preparation for the patient, and reinforce the importance of group therapy within the total treatment program. Continued research is needed to assess further the effectiveness of preparation for inpatients prior to group therapy and the nurses' role in preparation. PMID- 6267274 TI - They all felt wounded. PMID- 6267276 TI - [Brain teratology as a result of transplacental virus infection in ruminants]. AB - Various viruses relating to congenital brain teratology in ruminants are discussed. These include: bluetongue which may be responsible for porencephaly and hydranencephaly; Akabane disease, Rift Valley fever (mouse brain attenuated virus) and Wesselsbron disease (wild-type and mouse brain attenuated viruses) which can give rise to porencephaly, hydranencephaly, micrencephaly and cerebellar hypoplasia, and bovine viral diarrhoea-mucosal disease which results only in cerebellar hypoplasia. Certain foetal, maternal and virological factors that might have an effect on the pathogenesis of viral teratogenesis are briefly reviewed. Mention is also made of the different diagnostic procedures that can be used such as, gross and histopathological examination, virus isolation and serology. PMID- 6267277 TI - Inhibition of the renin-angiotensin system. A new approach to the therapy of hypertension. PMID- 6267275 TI - Constipation--a simple approach to treatment. AB - A simple method of treating patients with constipation is outlined and has been used successfully in 40 patients with severe primary constipation or constipation associated with diverticular disease. PMID- 6267278 TI - Photochemical inactivation of the angiotensin receptor of rabbit aorta by N alpha (2-nitro-5-azidobenzoyl)-[1-aspartic acid,5-isoleucine]angiotensin II. AB - The photoaffinity label N alpha-(2-nitro-5-azidobenzoyl)-[Asp1,Ile5]angiotensin II (nitroazidobenzoyl-angiotensin II) has a pD2 of 7.22 in the rabbit aortic strip assay compared to 8.44 for [Asp1,Ile5]angiotensin II and can be completely inhibited by [Sar1, Ala8]angiotensin II. Photolysis of a single dose of nitroazidobenzoyl-angiotensin II (0.1 microM) with aortic strips for 3 min with light of wavelengths of greater than 320 nm, followed by washing, resulted in loss of approximately 25% of the strip's response to a subsequent dose of nitroazidobenzoyl-angiotensin II. Photolysis of three consecutive doses of label resulted in loss of 62% of the strips response to a subsequent dose. Repetitive exposure to label in the dark and repetitive photolyses without label resulted in loss of no more than 20% of the strips ability to respond to angiotensin II. Photolysis with three consecutive doses of 0.1 microM nitroazidobenzoyl angiotensin II in the presence of 0.5 microM of the competitive inhibitor [Sar1,Ala8]angiotensin II decreased the observed inhibition from 62 to 22%. The long-lasting inhibition observed after photolysis with 0.1 microM nitroazidobenzoyl-angiotensin II therefore occurred via photolysis of some part of the nitroazidobenzoyl chromophore. This inhibition was mediated via the receptor that binds [Sar1,Ala8]angiotensin II and, therefore, angiotensin II. PMID- 6267279 TI - Potential thyroliberin affinity labels. 1. Chloroacetyl-substituted phenylalanylpyrrolidines. AB - Six analogues of thyroliberin (TRH) that have a chloroacetyl substituent at the amino terminus have been prepared as potential affinity labels for the TRH receptor. These compounds are N-(chloroacetyl)-L-alanyl-L-phenylalanylpyrrolidine (ClAc-Ala-Phe-Pyrr; 14), N-[m-(chloroacetyl)benzoyl]-L-phenylalanylpyrrolidine (m ClAcBz-Phe-Pyrr; 11a), N-[m-(chloroacetyl)benzoyl]-L-alanyl-L phenylalanylpyrrolidine (m-ClAcBz-Ala-Phe-Pyrr; 15a), N-[p-(chloroacetyl)benzoyl] L-phenylalanylpyrrolidine (p-ClAcBz-Phe-Pyrr; 11b), and N-[p (chloroacetyl)benzoyl]-L-alanyl-L-phenylalanylpyrrolidine (p-ClAcBz-Ala-Phe-Pyrr; 15b). Pyroglutamyl-L-phenylalanylpyrrolidine was also synthesized as a model agonist. Weak agonist activity was observed for 11a, 11b, and 15b. These three analogues do not contain the amide group of the pyroglutamyl moiety that was previously thought to be essential for intrinsic activity. No significant antagonist activity was observed for these compounds at the doses tested. PMID- 6267280 TI - Synthesis and antiviral activity of 5-[(cyanomethylene)oxy]-2'-deoxyuridine. AB - To study the influence of substitution of CN for C identical to CH in the anti herpes virus nucleoside 5-(propynyloxy)-2'-deoxyuridine (1), 5 [(cyanomethylene)oxy]-2'-deoxyuridine (2) was prepared. When the potassium salt of 5-hydroxy-2'-deoxyuridine was reacted with iodoacetonitrile in dry DMF, the bisalkylated product 3-(cyanomethyl)-5-[(cyanomethylene)oxy]-2'-deoxyuridine (3) was the major product with a lesser amount of 3-(cyanomethyl)-5-hydroxy-2' deoxyuridine (5) and only a trace amount of the desired product (2). In contrast, when 5-hydroxy-2'-deoxyuridine was alkylated in water in the presence of 1 equiv of KOH, compound 2 was the major product. In cultures of primary rabbit kidney (PRK) cells, compound 2 showed an anti-herpes virus activity that was comparable to that of 1 and ara-A. Compound 2 did not inhibit incorporation of [Me-3H]dThd or [1',2'-3H]dUrd into DNA of PRK cells; however, its anti-herpes virus activity was completely prevented upon the addition of either dThd or dUrd. PMID- 6267281 TI - Chemically reactive estrogens: synthesis and estrogen receptor interactions of hexestrol ether derivatives and 4-substituted deoxyhexestrol derivatives bearing alkylating functions. AB - A series of chemically reactive derivatives of the nonsteroidal estrogen hexestrol have been synthesized as potential affinity labels for the estrogen receptor or as cytotoxic agents with selective activity against receptor containing cells. These compounds are hexestrol ethers with halo ketone, halohydrin, or epoxide functions or 4-substituted deoxyhexestrols with halo ketone, benzyl halide, nitro, azide, sulfonyl fluoride, or sulfonyl azide groups. The alkylating activity of the electrophilic derivatives was measured using the colorimetric reagent nitrobenzylpyridine, the bromo derivatives being considerably more reactive than the chloro ones. Their reversible binding to the lamb uterine estrogen receptor was measured by competitive binding assays, and their irreversible reaction with receptor was measured by exchange assays that determine the rate and extent of receptor inactivation. In general, monoetherification of hexestrol or substitution of deoxyhexestrol produces compounds with relatively low affinity for the estrogen receptor (0.3-10% that of estradiol). Most of the electrophilic derivatives are rapid and effective inactivators of receptor (24-70% inactivation within 0.5-5 h at 25 degrees C). Of the photosensitive derivatives, 4-azidodeoxyhexestrol appears to be the most efficient receptor inactivator (49%). The high reactivity of these compounds toward the estrogen receptor and the lack of interference by their reaction with other cellular nucleophiles suggest that these compounds may be useful as affinity-labeling agents or as selective cytotoxic agents in intact systems. PMID- 6267282 TI - Synthesis and antitumor activity of simple vinyl and alpha-methylene-gamma butyrolactone sulfonate esters and silyl enol ethers. AB - A number of simple silyl enol ethers and vinyl trifluoromethanesulfonates, a relatively new class of organic compounds capable of undergoing alkylation by a nucleophilic addition-elimination process, were evaluated in the P388 lymphocytic leukemia system. No activity (ILS = 8-22%) was observed in the simple vinyl derivatives. Some activity (ILS = 20-42%) was observed for a series of siloxy and sulfonate (CH3SO2 and CF3SO3) functionalized alpha-methylene lactone systems. The enhanced activity of the functionalized systems over the parent methylene lactone is ascribed to a possible irreversible alkylation by cellular nucleophiles via a nucleophilic addition-elimination process. PMID- 6267283 TI - Pyrimidine acyclic nucleosides. 5-Substituted 1-[(2-aminoethoxy)methyl]uracils as candidate antivirals. AB - Several 5-substituted analogues of the acyclic aminonucleoside 1-[2 aminoethoxy)methyl]uracil (5) were prepared for evaluation as antivirals. The uracil and thymine analogues were prepared in two steps from N-[2 (chloromethoxy)ethyl]phthalimide (1). The 5-chloro, 5-bromo, and 5-iodo analogues were prepared by halogenation of 5. These acyclic aminonucleosides exhibited neither cell toxicity nor antiviral activity. This is compatible with their lack of substrate properties toward herpes simplex virus thymidine kinase. PMID- 6267285 TI - A K+-selective, three-state channel from fragmented sarcoplasmic reticulum of frog leg muscle. AB - Sarcoplasmic reticulum (SR) vesicles from frog leg muscle were fused with a planar phospholipid bilayer by a method described previously for rabbit SR. As a result of the fusion, K+-selective conduction channels are inserted into the bilayer. Unlike the two-state rabbit channel, the frog channel displays three states: a nonconducting ("closed") state and two conducting states "alpha" and "beta". In 0.1 M K+ the single-channel conductances are 50 and 150 pS for alpha and beta, respectively. The probabilities of appearance of the three states are voltage-dependent, and transitions between the closed and beta states proceed through the alpha state. Both open states follow a quantitatively identical selectivity sequence in channel conductance: K+ greater than NH4+ greater than Rb+ greater than Na+ greater than Li+ greater than Cs+. Both open states are blocked by Cs+ asymmetrically in a voltage-dependent manner. The zero-voltage dissociation constant for blocking is the same for both open states, but the voltage-dependences of the Cs+ block for the two states differ in a way suggesting that the Cs+ blocking site is located more deeply inside the membrane in the beta than in the alpha state. PMID- 6267284 TI - The use of gene fusions of study bacterial transport proteins. AB - The transport of solutes by bacteria has been studied for about thirty years. Early experiments on amino acid entry and galactoside accumulation provided concrete evidence that bacteria possessed specific transport systems and that these were subject to regulation. Since than a large number of transport systems have been discovered and studied extensively. Many of these use entirely different strategies for capturing or accumulating substrates. This diversity reflects variation in the availability of nutrients an ions in the different environments tolerated and inhabited by microorganisms. Examination of a few bacterial transport systems provides an opportunity to gain insight into a wide range of topics in the area of membrane transport. These include: the identification of carrier proteins and their arrangement in the membrane, the regulation of transport protein synthesis by environmental factors, and the localization of transport proteins to their extracytoplasmic destinations. It has been possible to construct a number of bacterial strains in which the gene (lacZ) which codes for the cytoplasmic enzyme beta-galactosidase is fused to genes which code for transport proteins. The following article is intended to illustrate how these gene fusions have been used to study the regulation and structure of transport proteins in Escherichia coli. PMID- 6267287 TI - Multicentric endobronchial granular cell myoblastoma. PMID- 6267286 TI - H+/ATP stoichiometry for the gastric (K+ + H+)-ATPase. AB - The initial rate of ATP-dependent proton uptake by hog gastric vesicles was measured at pH's between 6.1 and 6.9 by measuring the loss of protons from the external space with a glass electrode. The apparent rates of proton loss were corrected for scalar proton production due to ATP hydrolysis. For vesicles in 150 mM KCl and pH 6.1, corrected rates of proton uptake and ATP hydrolysis were 639 +/- 84 and 619 +/- 65 nmol/min x mg protein, respectively, giving an H+/ATP ratio of 1.03 +/- .07. Furthermore, at all pH's tested the ratio of the rate of proton uptake to the rate of ATP hydrolysis was not significantly different than 1.0. No proton uptake (less than 10 nmol/min x mg protein) was exhibited by vesicles in 159 mM NaCl at pH 6.1 despite ATP hydrolysis of 187 +/- 46 nmol/min x mg (nonproductive hydrolysis). Comparison of the rates of proton transport and ATP hydrolysis in various mixture of KCl and NaCl showed that the H+/ATP stoichiometries were not significantly different than 1.0 at all concentrations of K+ greater than 10 mM. This fact suggests that the nonproductive rate is vanishingly small at these concentrations, implying that the measured H+/ATP stoichiometry is equal to the enzymatic stoichiometry. This result shows that the isolated gastric (K+ + H+)-ATPase is thermodynamically capable of forming the observed proton gradient of the stomach. PMID- 6267288 TI - The ribosomal DNA of Calliphora erythrocephala; and analysis of hybrid plasmids containing ribosomal DNA. PMID- 6267289 TI - Tn903 induces inverted duplications in the chromosome of bacteriophage lambda. PMID- 6267290 TI - Analysis of double-helix motions with spin-labeled probes: binding geometry and the limit of torsional elasticity. PMID- 6267291 TI - Binding of a simian virus 40 T antigen-related protein to DNA. PMID- 6267292 TI - Preliminary x-ray diffraction studies of EcoRI restriction endonuclease-DNA complex. PMID- 6267293 TI - Studies on the biochemical basis of mutation VI. Selection and characterization of a new bacteriophage T4 mutator DNA polymerase. PMID- 6267295 TI - The DNA sequence recognised by the HinfIII restriction endonuclease. PMID- 6267294 TI - Genetic fusions that place the lactose genes under histidine operon control. PMID- 6267296 TI - Length variation in the non-transcribed spacer of Calliphora erythrocephala ribosomal DNA is due to a 350 base-pair repeat. PMID- 6267297 TI - Clustering of mutations inactivating a Chi recombinational hotspot. PMID- 6267298 TI - Characterization of initiator RNA from replicating simian virus 40 DNA synthesized in isolated nuclei. PMID- 6267299 TI - Structure analysis of three T7 late mRNA ribosome binding sites. PMID- 6267300 TI - Differential activities of putative subsarcolemmal and interfibrillar mitochondria from cardiac muscle. PMID- 6267301 TI - Temporal changes in adenylate cyclase activity in acutely ischemic dog heart: evidence of functional subunit damage. PMID- 6267302 TI - Tetrodotoxin sensitivity in the developing and adult chick heart. PMID- 6267304 TI - Mitochondria isolated from dispersed adult rat cardiac myocytes. PMID- 6267305 TI - Proton and free oxygen radical interaction with the calcium transport system of cardiac sarcoplasmic reticulum. PMID- 6267303 TI - Adriamycin Cardiotoxicity: possible pathogenic mechanisms. PMID- 6267306 TI - Mediation of polyamine-induced decrease of cyclic AMP content by cyclic AMP phosphodiesterase in chick heart cell cultures. PMID- 6267307 TI - Cardiac glycoside binding to the Na/K-ATPase in the intact myocardial cell: electrophysiological measurement of chemical kinetics. PMID- 6267308 TI - The evolution of a family of short interspersed repeats in primate DNA. AB - Human DNA contains 300 nucleotide interspersed repeated sequences which mostly belong to a single family of sequences called the Alu family. This work examines the evolution of this family of sequences in primates. Bonnet monkey (Macaque radiata) DNA contains a predominant family of 300 nucleotide repeats which has nearly the same restriction map as the human Alu family and which hybridizes to human Alu family repeats under Southern blotting conditions. Prosimian (Galago crassicaudatus pangeniesis) DNA also contains a prominent group of 300 nucleotide long repeated sequences which does not have the same restriction sites as the human Alu family but which does hybridize to the human Alu family under reduced stringency conditions. PMID- 6267309 TI - An improved method for estimating sequence divergence of DNA using restriction endonuclease mappings. AB - The method proposed by Kaplan and Langley for estimating the extent of sequence divergence between related DNA's using restriction endonuclease maps is modified so that the estimates are easier to compute. In the two-species case, these modifications lead via a maximum likelihood approach to an estimate which is closely related to one recently suggested by Nei and Li (1979) and Gotoh et al. (1979). Simulation studies show that the modified estimates are comparable to those of Kaplan and Langley, providing that there is sufficient homology in the DNA segments of the related species. The M-species case, M greater than or equal to 3, is also discussed. PMID- 6267310 TI - The effect of poly(C) on the formation of peptide bones from the 2'(3')-glycyl ester of a guanosine nucleotide. PMID- 6267311 TI - Evolution of cytochrome C investigated by the maximum parsimony method. AB - Rates of evolution for cytochrome c over the past one billion years were calculated from a maximum parsimony dendrogram which approximates the phylogeny of 87 lineages. Two periods of evolutionary acceleration and deceleration apparently occurred for the cytochrome c molecule. The tempo of evolutionary change indicated by this analysis was compared to the patterns of acceleration and deceleration in the ancestry of several other proteins. The synchrony of these tempos of molecular change supports the notion that rapid genetic evolution accompanied periods of major adaptive radiations. Rates of change at different time in several structural-functional areas of cytochrome c were also investigated in order to test the Darwinian hypothesis that during periods of rapid evolution, functional sites accumulate proportionately more substitutions than areas with no known functions. Rates of change in four proposed functional groupings of sites were therefore compared to rates in areas of unknown function for several different time periods. This analysis revealed a significant increase in the rate of evolution for sites associated with the regions of cytochrome c oxidase and reductase interaction during the period between the emergence of the eutherian ancestor to the emergence of the anthropoid ancestor. PMID- 6267313 TI - A simulation study on Nei and Li's model for estimating DNA divergence from restriction enzyme maps. AB - A simulation study has been conducted to check the accuracy of Nei and Li's (1979) formulas for the mean and variance of the proportion (S) of identical restriction sites between two DNA sequences and for estimating the mean and variance of the number (delta) of base substitutions per nucleotide site between two DNA sequences. The results show that these formulas are quite accurate as long as the probability of S becoming zero is negligibly. In addition to the simulation, approximate formulas have also been obtained for the probability for S to become zero at time t and for the contribution to S due to parallel mutation. PMID- 6267312 TI - The use of restriction endonucleases to measure mitochondrial DNA sequence relatedness in natural populations. III. Techniques and potential applications. AB - Restriction endonucleases and agarose gel electrophoresis have been used to demonstrate extensive nucleotide sequence diversity in mitochondrial DNA (mtDNA) within and between conspecific populations of rodents and other mammals. Cleavage of mtDNA samples with a relatively small number of endonucleases provides information concerning the phylogenetic relatedness of individual organisms which cannot now be readily obtained by any other type of molecular analysis. This information is qualitatively different from that available from the study of nuclear genes or gene products because the mitochondrial genome is inherited intact from the female parent and is not altered by recombination or meiotic segregation. The requirements for large tissue samples and laborious DNA purification procedures have imposed severe limitations on the kinds of population surveys in which this technique could be utilized. Here, we show that these difficulties can be overcome by using DNA-DNA hybridization to detect minute amounts of mtDNA in crude tissue fractions which can be more easily and rapidly prepared from very small amounts of tissue without the use of expensive and immobile laboratory equipment. The techniques are described in detail in an effort to make restriction analysis of mtDNA available to biologists who may be unfamiliar with current DNA technology. PMID- 6267314 TI - Spin label studies of erythrocytes with abnormal lipid composition: comparison of red cells in a hereditary hemolytic syndrome and lecithin: cholesterol acyltransferase deficiency. AB - Erythrocytes from patients with familial lecithin : cholesterol acyltransferase (LCAT) deficiency have been shown to exhibit an increase in membrane fluidity which is surprisingly small in view of the extensive alterations both in membrane lipid composition (namely, an elevation in cholesterol and phosphatidylcholine contents as well as a decrease in phosphatidylethanolamine) and in the functional properties of these cells. In the hope of deriving some information concerning the interrelationship between the structural and functional abnormalities, we have used the spin probe 5-doxyl stearic acid to investigate the temperature dependent fluidity properties of red cells from two patients with a hereditary hemolytic syndrome (HHS) whose red cells are also characterized by qualitatively similar alterations in phosphatidylcholine and phosphatidylethanolamine but, unlike those in LCAT deficiency, have relatively normal levels of membrane cholesterol. A small increase in membrane fluidity of HHS erythrocytes equivalent to that previously observed in LCAT deficiency was found, indicating that membrane cholesterol level does not exert an important modulatory influence on membrane fluidity in these cells. It is concluded that while the distinct patterns of structural and functional erythrocyte alterations in these two disorders cannot be explained on the basis of differences in bulk membrane fluidity, the marginally increased fluidity may underlie the abnormalities in osmotic fragility and membrane p-nitrophenylphosphatase activity which are shared in common by both types of modified red cells. PMID- 6267315 TI - Subcellular structures involved in internalization and degradation of epidermal growth factor. AB - Epidermal Growth Factor (EGF), a small polypeptide which acts as a mitogen for many cell types, has previously been shown to bind to a specific plasma membrane receptor on 3T3 cells. If 125I-EGF is bound to 3T3 cells for one hour at 4 degrees C, it remains predominantly associated with the plasma membrane containing fractions obtained by subjecting cell supernatants to equilibrium sedimentation on sucrose gradients. When binding is followed by a 10-minute incubation at 37 degrees C, over 50% of the 125I-EGF is associated with two internal membrane-containing peaks having higher densities than the plasma membrane. After one hour at 37 degrees C, over 80% of the 125I-EGF is degraded and removed from the cells. The most rapidly labeled internal peak corresponds in density to brain-coated vesicles (CVs). Antiserum prepared against coated vesicles from brain precipitates the 125I-EGF in this peak. In addition, CVs containing 125I-EGF can be co-purified from 3T3 cells exposed to 125I-EGF, using brain as a carrier. Several lines of evidence suggest that the other 125I-EGF labeled intracellular peak is 125I-EGF in lysosomes. These results provide kinetic and biochemical evidence for a unidirectional pathway for EGF catabolism by 3T3 cells. EGF first binds to the plasma membrane bound receptors, is then moved to the cytoplasm in CVs, and finally appears in lysosomes, where it is degraded and released from the cells. Ten-millimolar NH4Cl blocks lysosomal hydrolysis of EGF almost completely. Subsequently, EGF internalization is inhibited. This finding suggests that the pathway for EGF internalization and degradation is tightly coupled. PMID- 6267316 TI - Multiplication stimulating activity (MSA) from the BRL 3A rat liver cell line: relation to human somatomedins and insulin. AB - The properties of multiplication stimulating activity (MSA), an insulin-like growth factor (somatomedin) purified from culture medium conditioned by the BRL 3A rat liver cell line are summarized. The relationship of MSA to somatomedins purified from human and rat plasma are considered. MSA appears to be the predominant somatomedin in fetal rat serum, but a minor component of adult rat somatomedin. In vitro biological effects of MSA and insulin in adipocytes, fibroblasts and chondrocytes are examined to determine whether they are mediated by insulin receptors or insulin-like growth factor receptors. The possible relationship of a primary defect of insulin receptors observed in fibroblasts from a patient with the rare genetic disorder, leprechaunism, to intrauterine growth retardation is discussed. PMID- 6267317 TI - Transforming growth factors (TGFs): properties and possible mechanisms of action. AB - Transforming growth factors (TGFs) are growth-promoting polypeptides that cause phenotypic transformation and anchorage-independent growth of normal cells. They have been isolated from several human and animal carcinoma and sarcoma cells. One TGF is sarcoma growth factor (SGF) which is released by murine sarcoma virus transformed cells. The TGFs interact with epidermal growth factor (EGF) cell membrane receptors. TGFs are not detectable in culture fluids from cells which contain high numbers of free EGF cell membrane receptors. SGF acts as a tumor promoter in cell culture systems and its effect on the transformed phenotype is blocked by retinoids (vitamin A and synthetic analogs). The production of TGFs by transformed cells and the responses of normal cells to the addition of TGFs to the culture medium raise the possibility that cells "autostimulate" their own growth by releasing factors that rebind at the cell surface. The term "autocrine secretion" has been proposed for this type of situation where a cell secretes a hormone-like substance for which it has external cell membrane receptors. The autocrine concept may provide a partial explanation for some aspects of tumor cell progression. PMID- 6267318 TI - Hepatocellular carcinoma- etiologic considerations: a review of the literature. AB - There are an estimated 120 million hepatitis B virus carriers worldwide. More than 200,000 of these are in the United States. A higher incidence of active hepatitis B virus infection has been observed in patients with hepatocellular carcinoma than in controls, in all geographical regions. This paper reviews the world literature on the relationship of hepatitis B virus to the pathogenesis of hepatocellular carcinoma. PMID- 6267319 TI - Serum protein concentrations and respiratory tract abnormalities following short term exposure to amosite: a comparison between former asbestos workers and unexposed controls. AB - A group of 176 former asbestos workers and 76 unexposed controls of similar age were evaluated and compared for concentrations of serum immunoglobulins, alpha 1 antitrypsin, carcinoembryonic antigen (CEA), pulmonary function, radiographic appearance of the lungs, rales, cellular atypia and ferruginous bodies in sputum, and smoking habits. Test subjects were evaluated as a single group and also according to years of exposure to asbestos. Both test and control populations were independently subjects to parametric and nonparametric correlation analyses. Partial correlations were also determined for both groups after controlling for age, race, sex and smoking habits. Analysis of variance was used to compare test and control groups. Smoking, particularly heavy smoking, was an important variable influencing abnormalities of the respiratory tract and CEA in former asbestos workers but not in controls. Except for immunoglobulin A (IgA), serum proteins, CEA, and alpha 1-antitrypsin were not significantly different between test and control subjects. Analysis of variance revealed significant increases between test and control groups for cellular atypia, X-ray abnormalities, rales, and pulmonary restriction. Partial correlation analysis of the asbestos-exposed group revealed important correlations between ferruginous bodies in sputum, rales, and radiographic appearance of the lungs. PMID- 6267320 TI - How good are the numbers for cigarette tar at predicting deliveries of carbon monoxide, hydrogen cyanide, and acrolein? AB - Simple and multiple linear regression analyses were performed on the tar, nicotine, CO, HCN, and acrolein deliveries of 98 brands of commercially available Canadian cigarettes. Simple linear regressions of CO, HCN, and acrolein on tar and of acrolein on CO were not significant at the 5% level for plain cigarettes; all other regressions were very strongly significant (p less than 0.01). In addition there was strong statistical evidence that filter, vented filter, and plain cigarettes have different regression relations and different levels of precision associated with the regression parameters. With respect to CO, tar level could predict the corresponding CO value only within 3.9 mg (filter), 1.9 mg (vented filter), and 3.1 mg (plain). These results show that tar delivery alone is an inadequate predictor of gas-phase constituents such as CO. Information concerning these constituents is best conveyed by an analytically determined value for each component. PMID- 6267321 TI - Alterations in hepatic mixed-function oxidase activity of rainbow trout after acute treatment with polybrominated biphenyl isomers and FireMaster BP-6. AB - The effects of FireMaster BP-6 and several pure isomers on hepatic microsomal mixed-function oxidase (MFO) activity in rainbow trout have been investigated. After one parenteral injection of these agents at 150 mg/kg and sacrifice 5 d later, there was no elevation of hepatic cytochrome P-450. The noncoplanar isomers 2,4,5,2',4',5'-hexa and 2,3,4,5,2',4',5'-heptabromobiphenyl did not increase any MFO activity generally associated with an increase in cytochrome P 450 levels, including the dealkylations of ethoxycoumarin and benzphetamine. The coplanar isomer 3,4,5,3',4',5'-hexabromobiphenyl produced an increase in O deethylation of both ethoxycoumarin and ethoxyresorufin, suggesting enhancement of cytochrome P-448 associated activity, but produced no increase in benzphetamine N-dealkylation. The "mixed inducer" 2,4,5,3',4',5' hexabromobiphenyl, produced a small but insignificant elevation of cytochrome P 448 associated MFO activities and no increase in cytochrome P-450 associated activities. At both 150 and 500 mg/kg, the commercial mixture of polybrominated biphenyls FireMaster BP-6 produced marked elevations of both ethoxycoumarin and ethoxy-resorufin dealkylations but had no effect on demethylation of benzphetamine. When microsomes from rainbow trout treated with FireMaster BP-6 were examined electrophoretically, A coomassie Blue-staining band at 57,000 daltons was intensified, as seen after treatment of fish with the cytochrome P 448 inducer beta-naphthoflavone. It is concluded that coplanar polybrominated isomers produce an induction of hepatic cytochrome P-448 associated activity, while noncoplanar isomers are ineffective as inducers of cytochrome P-450 related MFO activities in rainbow trout. PMID- 6267322 TI - Influence of sulfur dioxide on metabolism and distribution of benzo[a]pyrene in isolated perfused rabbit lung. AB - An isolated perfused lung [IPL) preparation was used to investigate the effects of SO2 (1-2 ppm) on the metabolism of benzo[a]pyrene (BaP), a ubiquitous potent carcinogen that has been associated with the increased incidence of a human bronchiogenic carcinoma in occupational and urban populations. [14C]BaP, with and without crude air particulate (CAP), was administered intratracheally to the IPL in conjunction with SO2 or after pretreatment of the whole animal with SO2. Metabolites were isolated from serial blood samples up to 3 h after the administration of [14C]BaP to the IPL. Metabolites were also isolated from lung tissue, washout fluid, macrophage, and trachea and bronchi at the end of the perfusion at 180 min. Patterns of BaP metabolites were determined by thin-layer and high-performance liquid chromatography and scintillation counting. SO2 given in conjunction with BaP on the IPL or given to the whole animal followed by BaP on the IPL, in comparison with BaP only on the IPL, resulted in a twofold increase in the total rate of appearance of metabolites of BaP in the blood with changes in the metabolic pattern. SO2 given in conjunction with BaP and CAP on the IPL, in comparison with BaP plus SO2 on the IPL, resulted in a threefold decrease in the total rate of appearance of metabolites of BaP in the blood with changes in the metabolic pattern. PMID- 6267323 TI - Uptake of benzo[a]pyrene by gonadal tissue of flatfish (family Pleuronectidae) and its effects on subsequent egg development. AB - Accumulation of benzo[a]pyrene (BaP) by sexually mature flatfish gonad, its transfer to developing gametes, and its subsequent effects on developing embryos were studied. Thin-layer chromatography revealed both unmetabolized BaP and polar metabolites in the ovary, wolffian ducts, oocytes, and semen of English sole 24 h after ip injection with 200 microCi [3H]BaP. Concentrations of BaP and its metabolites were 3-11 times higher in oocytes and semen than in gonadal tissue. Fertilized eggs from flathead sole that had been fed 4.0 mg BaP 5 h before spawning demonstrated a significantly lower (p less than 0.001) hatching success (11.9%) than eggs from control fish (56.6%). Morphological abnormalities were found in only 1.6% of control embryos but in 5.6% of embryos from treated females. PMID- 6267324 TI - Electron microscopic studies on the incorporation of human spermatozoa into mouse fibroblasts following Sendai virus fusion. PMID- 6267325 TI - A minibead method to study cell surface receptors for various proteins coupled to latex particles. PMID- 6267326 TI - Malignancies associated with renal transplant: first case report of a nephroblastoma occurring in an adult host kidney. AB - The increased incidence of malignancies after renal transplantation has been well documented. We describe the first reported case of a nephroblastoma (Wilms tumor) occurring in the host kidney of an adult after renal transplantation. PMID- 6267327 TI - A case of prostatic malacoplakia. AB - Prostatic malacoplakia is an extremely rare disease. We report a case of malacoplakia of the prostate and review the 21 cases previously reported, including 4 in our country and 17 in other countries. PMID- 6267328 TI - Virus in Papilloma. PMID- 6267329 TI - Prevalence of poliovirus neutralizing antibodies in young adult women. PMID- 6267330 TI - Is there a need of "catch-up' polio vaccination in preadolescence? PMID- 6267331 TI - Diet and diabetes. PMID- 6267332 TI - Pinpointing the cause of mucus production. PMID- 6267333 TI - Femoral neuropathy and anticoagulant therapy. PMID- 6267334 TI - Experimental coxsackie B virus myocarditis in mice: 18 month histopathological and virological study. AB - In a series of experimental studies to test the hypothesis that idiopathic cardiomyopathy in man represents a sequela of virus myocarditis, coxsackie B 1, 3 or 5 virus was inoculated into ICR mice with two different amounts, that is, a small amount (0.1 ml of 10(5.5) TCID50/ml) and a large amount (0.1 ml of 10(7.5) TCID50/ml). Histopathological and immunofluorescent studies of the heart, analysis of the antibody titers in sera and evaluation of the virus concentration in various organs including the heart were carried out in an acute (up to the 21st day) and chronic phase (up to the 18th month) of the experiment. A small amount of coxsackie B 1 or 5 virus did not cause myocarditis, while a large amount of either virus rarely induced mild myocarditis. A small amount of coxsackie B 3 virus frequently caused mild myocarditis without obvious residual pathologic changes of the heart, while a large amount of the same virus always caused acute and severe myocarditis. In these animals, acute myocardial changes are almost in agreement with those in previous investigations except for capillary thrombi. The virus was isolated from the heart with higher titers than from other organs and identified in some cardiocytes by immunofluorescent study until the 14th day. Neutralizing antibody in sera appeared on the 7th day and remained for several months. Approximately two thirds of these mice left no significant myocardial lesions, whereas about one third of them which probably had extensive myocardial lesions in the acute phase developed significant myocardial fibrosis with calcification in the chronic phase. These lesions appeared to become larger after the 6th month. In and around the fibrotic lesions, atrophy, hypertrophy and/or disarray of myocardial fibers were observed. These hearts did not show hypertrophy or dilatation but their histologic findings resembled those seen in some cases of congestive cardiomyopathy except for severe calcification in the myocardium. PMID- 6267335 TI - [Potassium adaptation]. PMID- 6267336 TI - [Catecholamines and potassium metabolism]. PMID- 6267337 TI - [Malignant insulinoma with high ratio of proinsulin-like component inside the tumor--a case report]. PMID- 6267338 TI - [Clinicopathological studies in patients with hepatocellular carcinoma. V. Analysis of the numbers of parameters for prognosis forecasting (author's transl)]. PMID- 6267339 TI - [Clinicopathological studies in patients with hepatocellular carcinoma. VI. Illustration of clinical stages by factor score (author's transl)]. PMID- 6267340 TI - Symphalangism associated with synostosis of carpus and/or tarsus. PMID- 6267341 TI - Ca2+ removal effects on bullfrog gastric mucosa in the presence of drugs. AB - Bullfrog gastric mucosa can secrete acid in vitro for more than 24 hr. In Ca2+ deficient media, the acid secretion measured by pH stat method gradually decreased to cease about 200 min after the start of immersion in the media. When A23187 or quinidine, which are known to mobilize Ca2+ from the intracellular pools, was present on the submucosal side, a prolongation of the duration of acid secretion in the absence of Ca2+ was found. Dibutyl c-AMP also induced a similar prolongation. Histamine or theophylline not only prolonged the duration of acid secretion but also transiently increased the acid secretory rate over the control level. Based upon the known fact that there are different intracellular Ca2+ compartments, i.e, one related to the process of acid secretion and the other to the maintenance of junctional complexes, the present results of drug effects were discussed especially in regard to their Ca2+ mobilizing effects. Cessation of acid secretion in a K+- and Ca2+-deficient solution occurred much more quickly than that in a Ca2+-deficient or a K+-deficient medium. PMID- 6267342 TI - [Smooth muscle and cardiac glycosides (author's transl)]. AB - Actions of cardiac glycosides (C.G.) on smooth muscles are reviewed. 1. C.G. inhibit the Na-K ATPase of smooth muscle membrane, though the degree and mode of the inhibition vary among the types of smooth muscles. 2. The uptake of C.G. by smooth muscles has been reported to be influenced by K+, Na, ATP, and temperature. The difference between the uptake and its effect can be observed. 3. Intracellular K concentration decreased and intracellular Na concentration increased by the treatment with C.G. 4. They depolarized the membrane; the action being affected by extracellular ion concentration. An increase in spike discharges is observed. 5. C.G. potentiate or inhibit the concentrations of smooth muscles, depending on the types of smooth muscles and the causes of the contraction. C.G. can also cause transient contraction of smooth muscle. 6. C.G. influence the Ca content and Ca movements of smooth muscles. 7. C.G. cause the release of noradrenaline, acetylcholine, or prostaglandins. These substances can affect the contractile responses of smooth muscles. PMID- 6267344 TI - Lymphoproliferative responses to mouse mammary tumor virus in lymphocyte subsets of breast cancer patients. AB - Altered immunologic reactions were observed in breast cancer patients as compared to those in normal subjects. Lymphoproliferative responses to murine mammary tumor virus (MuMTV) were significantly enhanced in peripheral blood mononuclear cells from patients with metastatic disease. These reactivities occurred with mammary tumor virus purified from either mouse milk or infected feline kidney cells but not with Rauscher murine leukemia virus. For the assessment of the role of peripheral blood mononuclear leukocyte subpopulations in the responsiveness to MuMTV, the cell preparations were fractionated according to their ability to form spontaneous rosettes with sheep red blood cells (E-rosettes). The effectiveness of the separation was ascertained by means of cell surface markers, i.e., presence of surface immunoglobulins or a T-cell marker. Leu-1 antigen, and mitogen-induced blastogenesis. The responsiveness to the MuMTV antigen(s) was associated with the T-cell subset, identified as the E-rosetting. Leu-1-positive, and surface immunoglobulin-negative population. Although some subjects with the normal population gave positive reactions, the results reveal an apparent association between high levels of responsiveness to MuMTV within the T lymphocyte subset and breast cancer disease. PMID- 6267343 TI - Human breast carcinoma: fibrin deposits and desmoplasia. Inflammatory cell type and distribution. Microvasculature and infarction. AB - Study of 14 human infiltrating breast carcinomas revealed new features that shed light on the pathogenesis of tumor stroma formation and on host immunologic defense mechanisms. Fibrin deposits were observed in the stroma of all tumors, particularly at their growing edge. Fibrin may have contributed both to tumor angiogenesis and, with organization, to the formation of the fibrous stroma characteristic of these and other scirrhous carcinomas. We previously proposed similar mechanisms for several animal tumors. All breast carcinomas studied elicited some degree of lymphocytic response at the tumor periphery; lymphocytes penetrated the fibrous tumor stroma poorly, did not exit in significant numbers from central tumor vessels, and, even when greatly outnumbering tumor cells locally, appeared relatively ineffective at tumor cell killing. Microvascular endothelial cell damage was frequently observed and may have been responsible for zones of tumor infarction. Similar observations have been made in skin allografts and animal tumors where rejection was effected principally by microvascular damage and subsequent tissue infarction, not by lymphocyte contact with individual epithelial target cells. PMID- 6267345 TI - Increased sensitivity of murine leukemia virus-infected tumor cells to lymphocyte mediated cytotoxicity. AB - The cytotoxic sensitivity of murine leukemia virus (MuLV)-infected and noninfected fibrosarcoma cells in syngeneic inbred WKA/Hok rats was compared by in vitro cell-mediated 51Cr release cytotoxicity assay. A highly significant increase in cytotoxic sensitivity of target cells was observe in MuLV-infected tumor cells as compared with noninfected cells when spleen cells from syngeneic tumor-bearing hosts (TBH) were used as a source of effector lymphocytes. The cytotoxicity of spleen cells against MuLV-infected tumor cells was specifically directed to the tumor-associated antigen (TAA), but not to the virus-associated antigen. However, there was no quantitative difference in the amount of TAA on the cell membranes between virus-infected and noninfected tumor cells as measured by a quantitative absorption test of anti-TAA serum. The cytotoxic activity of spleen cells from TBH against MuLV-infected tumor cells was abrogated by the treatment of anti-T-serum plus complement and significantly decreased after trypsin treatment. Spleen cells from normal rats given injections of immune sera from TBH acquired the cytotoxic activity against MuLV-infected tumor cells. PMID- 6267346 TI - Carcinogen binding to various types of dietary fiber. AB - The percent of the carcinogen 1,2-dimethylhydrazine (DMH) bound to a variety of fibers, such as wheat bran, corn bran, citrus pulp, citrus pectin, and alfalfa, was examined at pH values ranging from 1 to 12. The percent of DMH bound to wheat bran increased from 4% at PH 1 to 55% at pH 2 to 77% at pH 12. A sharp rise in carcinogen binding to corn bran occurred between pH 5% of the DMH was bound and pH 8 where 51% of the DMH was bound. The percent of DMH bound to dehydrated citrus pulp also increased as the pH increased with 10% binding observed at pH 1 and with 57% binding observed at pH 12. Between pH 2 and pH 7, the percent of DMH bound to pectin decreased from 60 to 11%. As the pH became more basic, the percent of DMH bound to pectin increased to 42% at pH 12. The sharpest rise in the percent of DMH bound to alfalfa meal occurred between pH 10.5 and pH 12.0. Results from this experiment showed that the affinity to various types of dietary fibers for the colon carcinogen DMH was differentially affected by pH. These results suggested that the protective effect of certain types of dietary fiber against chemically induced colon cancer my in part be attributed to enhanced carcinogen binding by dietary fiber in the colon. PMID- 6267347 TI - [Myocardial carbohydrate metabolism in limited coronary blood flow]. AB - Dosaged restriction of coronary blood flow (by 30, 50, 70 and 90%) was reproduced for 30 minutes in dogs with a closed chest. In all degrees of coronary blood flow restriction the loss of glycogen, accumulation of lactic acid and cAMP (in reduction of blood flow by 50 and 70%) and activation of glycogenolysis, phosphorylase and phosphofructokinase were recorded in the zone of ischemia. The changes advanced with the deepening of ischemia. Similar, though less pronounced changes were found outside the ischemic zone. Marked metabolic shifts were disclosed in the right ventricle. The mechanisms of anaerobic oxidation activation in ischemia are discussed. PMID- 6267348 TI - Interrelationship between prostaglandins and renin release. PMID- 6267349 TI - Role of prostaglandins in renin secretion. PMID- 6267350 TI - Vasopressin-prostaglandin interactions in the regulation of epithelial cell permeability to water. PMID- 6267351 TI - Prostaglandins and water metabolism: a review with emphasis on in vivo studies. PMID- 6267352 TI - [Selective proximal vagotomy without gastric drainage in treating duodenal peptic ulcer]. PMID- 6267353 TI - [Specific local anesthesia: pharmacology, administration and clinical use (author's transl)]. AB - In order to achieve an optimal combination of principal and side effects of the various drugs used in local anesthesia, a thorough knowledge of pharmacology, anatomy and physiology is essential. The properties of the most commonly used short-acting (Lidocain) medium (Mepivacain) and long-acting (Bupivacain) local anesthetics are described, as well as the effect of the vasoconstrictors Adrenalin and Ornipressin, and of hyaluronidase. The advantages and drawbacks of the different application modalities are discussed. In clinical practice, the surgeon has to be aware of his particular local anesthetic needs at any given time and any stage of the operation, and should attempt to create ideal conditions by careful selection, combination and application of the different drugs. The choice is relatively easy in operations on the globe, the eye muscles and the lacrimal drainage system. In major lid operations, however, greater differentiation in the selection of drugs and methods of application is advisable. PMID- 6267354 TI - [Histopathology of nephroblastomas (author's transl)]. AB - Nephrectomy specimens from 42 patients with nephroblastoma were investigated. With the exception of one specimen (the patient had been treated preoperatively), all of the tumors were suitable for grading procedures. When the tumors were classified by the grading procedure of Lawler et al. (1975), the moderately tubulus-rich type++ was the most common (22 out of 41 patients). When the classification of Beckwith and Palmer (1978) was applied, the mixed type of nephroblastoma dominated correspondingly (19 out of 41 patients). Patients with an increased risk can be identified particularly well with the classification of Beckwith and Palmer. The following histologic features are indications of an unfavourable prognosis: focal or diffuse "anaplasia" of the tumor tissue, or a sarcomatous component in a stroma-rich nephroblastoma. The children with sarcomatous nephroblastoma (5 patients) were remarkably young (the oldest was 16 months of age), whereas the children with anaplastic nephroblastoma (3 patients) were much older (62, 67, and 72 months). In five children equivalents of the nephroblastomatosis complex (nodular renal blastema in all 5 patients, sclerosing metanephric hamartoma in 2 patients, and Wilms' tumorlet in one patient) were found in the non-infiltrated tissue of the same kidney. PMID- 6267355 TI - [Wilms' tumors: the actual standpoint (author's transl)]. AB - Treatment results in children with Wilms' tumors have remarkably improved during the past ten years. This is the most important aspect in modern Wilms' tumor research. Further, new etiologic factors have been identified. Modern diagnostic procedures (with special reference to an eventual preoperative treatment), aspects of "staging" and "grading", the changed prognosis and handling of bilateral tumors, the identification of infantile congeners of Wilms' tumors and the often realized optimal interdisciplinary cooperative treatment have allowed to design the former mostly fatal tumors as outstanding in clinical oncology. This paper summarizes the recent data available from the literature; several problems remain unresolved. Among open questions are a better preoperative diagnosis, standardization of treatment of stage-IV-patients, determination of the role of adriamycin in chemotherapy, and the comprehensive and thorough study of late effects. PMID- 6267356 TI - [Radiological diagnostics and radiotherapy in Wilms' tumor (author's transl)]. AB - The possibilities of diagnosing Wilms' tumor correctly have been greatly extended by the introduction of computerised tomography and ultrasonic examination. In view of the fact that Wilms' tumor is subjected to combined treatment involving chemotherapy, surgery and radiotherapy, it appears justified to reduce the dose to 20--30 Gy, depending upon the age of the child and the extension of the tumor. It is believed that preoperative radiotherapy will yield better surgical possibilities in large tumours. Radiotherapy can be omitted in infants in the stages I and II as well as in children in stage I. PMID- 6267357 TI - [Sonographic contributions to the diagnosis of Wilms' tumors (author's transl)]. PMID- 6267358 TI - [Bone metastases in Wilms' tumor in relation to histologic grading (author's transl)]. AB - 86 patients with Wilms' tumor were treated in Heidelberg between 1951 and 1980. Using the histopathologic grading according to Hardwick and Stowens the sarcomatous tumor type has an unfavorable prognosis. All the patients in stage III to V developed metastases. In contrast to other types of Wilms' tumor these sarcomatous tumors do metastasize to bones, not primarily to the lung. Boys up to 5 years are mostly affected by the tumor. These were "cold" lesions in bone scan using different radionuclides on skeletal osteolytic metastases, which is limiting the application of scans to detect bone metastases in Wilms' tumor. A more aggressive chemotherapy should be given to improve prognosis of the sarcomatous type of Wilms' tumor. PMID- 6267359 TI - [Aniridia and Wilms' tumor (Miller's syndrome)]. PMID- 6267360 TI - [Vitamin D 1980--a stocktaking (author's transl)]. AB - Vitamin D3 and its various metabolites have a central position in the regulation of the calcium- and phosphorus metabolism. Of special importance is 1,25 dihydroxyvitamin D3, which is almost exclusively synthesized in the kidney. Its production is dependent upon several hormonal stimuli and of course occurs normally only in intact renal tissue. The multifactorial regulation of its formation implies that a variety of diseases could cause disturbances in the metabolism of vitamin D. 1,25-dihydroxyvitamin D3 exerts its biological effects not only at the intestine, bone and kidney, but as well presumably in organs as the parathyroid glands, hypophysis, pancreas and skin. 24,25-dihydroxyvitamin D3- although its biological value is still in debate--represents possibly a second vitamin D-hormone of importance. Inspite of intensive research work the metabolic fate of vitamin D3 and its full biological significance is not yet entirely understood. PMID- 6267361 TI - Changes in tissue sensitivity to vasopressin in hereditary hypothalamic diabetes insipidus. AB - Specific binding of (125I) arg8-vasopressin to mononuclear phagocytes of the circulating blood was studied in 3 patients (one male, two females) with hereditary hypothalamic diabetes insipidus before, during and after therapy with 1-desamino-8-D-arginine vasopressin and compared with values of 15 normal donors (7 males, 8 females). Before therapy specific radioligand binding activity was considerably increased (0.3 +/- 0.08 fmoles/2.2 X 10(5) cells/ml) versus controls (0.23 +/- 0.04 fmoles/2.2 X 10(5) cells/ml). Increased binding was due to increase in receptor concentration per cell. In contrast, during treatment and after withdrawal of therapy the receptor binding activity was 0.1 +/- 0.05 fmoles/2.2 X 10(5) cells/ml. The dissociation constant (KD) for hormone binding before therapy (25 +/- 0.2 pM) was roughly identical with that of normal donors (24 +/- 0.8 pM), indicating insignificant changes in receptor affinity. During treatment and 48 h after withdrawal of therapy, however, the KD value was 11 +/- 0.45 pM, which amy be accounted for by an elevation in the binding affinity. We conclude that untreated patients with hereditary hypothalamic diabetes insipidus have increased tissue sensitivity to vasopressin, but have decreased binding capacity during and even two days after discontinuation of therapy, possibly as the result of 1-desamino-8-D arginine vasopressin-induced desensitization phenomena. PMID- 6267362 TI - [Myeloperoxidase activity in patients with complicated arteriosclerosis and in their relatives]. PMID- 6267363 TI - [Blood levels of pancreatic hormones, gastrin and cyclic adenosine monophosphate in peptic ulcer]. PMID- 6267364 TI - [The possible meanings of suffering]. PMID- 6267365 TI - [Meeting the sufferer: the caring relationship, occasion for a symbolic exchange]. PMID- 6267366 TI - [Pain sensation and suffering: physiological aspects]. PMID- 6267367 TI - [Not in agreement with M. Boyer's article: "Disquiet in nursing"]. PMID- 6267368 TI - [General nursing: hospital physician and concepts of the nursing profession]. PMID- 6267369 TI - [General nursing: observations on experiences from a soldier's viewpoint. Being a nurse in the Swiss Army]. PMID- 6267370 TI - [Psychiatric nursing: nursing also means empathy. Experiences in the nursing care of an epileptic patient]. PMID- 6267371 TI - Comparison of alkaline phosphatase and horseradish peroxidase conjugated antisera in the ELISA test for antibodies to reovirus 3, mouse hepatitis and Sendai viruses. PMID- 6267372 TI - Naturally occurring Yaba tumor in a baboon (Papio papio). PMID- 6267373 TI - Feline insular amyloid. Ultrastructural evidence for intracellular formation by nonendocrine cells. AB - The objective of this ultrastructural study in cats was to investigate the early relationship of pancreatic islet cells with amyloid deposits. We used pancreatic islets from six domestic cats with minimal and apparently early amyloid deposits. Although amyloid deposits were occasionally arranged perpendicularly to beta cells, and rarely within deep invaginations of these cells, there was no consistent or convincing relationship of extracellular fibrils to any of the major islet stricted to, nongranulated perivascular cells in islets from two of the cats. Small and relatively electron-dense amyloid inclusions contained compact arrays of parallel fibrils. Larger inclusions were more electron-lucent and had loosely and randomly arranged fibrils. Indirect evidence strongly suggested that the fibril-laden inclusions resulted from intracellular production rather than from phagocytosis. The definitive identity of these amyloid containing cells was not determined. However, these calls lacked secretory granules specific for known islet endocrine cell types and were topographically always located in close proximity to capillaries. The results of our study, therefore, do not directly support a morphologic association of amyloid fibril formation with typical islet endocrine cells. Our results do, however, draw attention to the possibility that nonendocrine cells play a key role in the pathogenesis of insular amyloidosis in the cat. PMID- 6267374 TI - Chromatographic analysis for delta1-tetrahydrocannabinol in blood and brain. PMID- 6267375 TI - Synovial sarcoma of abdominal wall: a case report and study of tumor fine structure. AB - A case of synovial sarcoma in the abdominal wall of a 50-year-old Iraqi woman is reported. The ultrastructure of the tumor has been studied. Eight other cases of synovial sarcoma in the abdominal wall reported in the English literature up to 1978 have been reviewed. Synovial sarcomas in the abdominal wall tend to occur with a much greater frequency in women, whereas such tumors occurring in the extremities or the neck are more common in men than woman. No ultrastructural studies of abdominal wall synovial sarcomas could be found in the English literature. The ultrastructural characters of this tumor are similar to those of such tumors arising in the usual sites and the neck. However, the present study has indicated that the light and dark cells reported by earlier workers are not limited solely to the epitheloid areas but are also present in the spindle cell zones. PMID- 6267377 TI - [The cardiac alpha-adrenoceptors]. PMID- 6267376 TI - Dimethyltriazenoimidazole carboxamide therapy of islet cell carcinoma of the pancreas. AB - Four patients with metastatic glucagonoma and one patient with metastatic diarrheogenic islet cell carcinoma of the pancreas were treated with dimethyltriazenoimidazole carboxamide (DTIC), 250 mg/M2 daily for five days repeated every four weeks. All patients responded clinically and chemically in one or more ways by a reduction in plasma glucagon levels, improved glucose tolerance, decreased measureable tumor, weight gain, and resolution of necrolytic migratory erythema and diarrhea. This experience and other cases from the literature call for the investigation of DTIC as the initial therapy in metastatic islet cell carcinoma of the pancreas and as being of possible benefit in other tumors of neuroendocrine origin. PMID- 6267378 TI - Refractory period fluid stimulation of right atria: a method for studying presynaptic receptors in cardiac autonomic transmission. AB - A method is described for measuring the atrial period or beat interval from the surface electrogram in isolated spontaneously contracting guinea pig right atria. Stimulation of parasympathetic and sympathetic nerve endings can be readily obtained by applying electrical field pulses across the atria during the atrial refractory period to prevent arrhythmia. In the presence of atropine, the atria respond to a single field pulse with a slight tachycardia that can be taken as a measure of the released transmitter norepinephrine. Because the effector response is mediated by a beta-adrenoreceptor, this preparation is particularly suited for the study of the pharmacology of presynaptic alpha-adrenoreceptors. The fall in period (tachycardia) to one-, two-, or four-field pulses delivered one per consecutive refractory period is linear, and the responses are reproducible for many hours. This biological system offers advantages in sensitivity and stability over methods employing radiolabeled norepinephrine in the study of presynaptic receptors in cardiac autonomic transmission. PMID- 6267379 TI - Interactions among carnosine, anserine, ophidine and copper in biochemical adaptation. PMID- 6267380 TI - A possible model for receptors in excitable membranes. PMID- 6267381 TI - Single file ion diffusion and the Schmoluchowski equation. PMID- 6267382 TI - [Improved pregnancy rates with ovulation stimulation using clomiphene and the effect of conjugated estrogens on the cervix]. AB - From a larger group of women treated which clomiphene 25 patients were selected who failed to conceive in spite of an indirect evidence of the ovulatory response and adequate luteal phase. Seventeen of them, who showed a distinct suppression of preovulatory reaction according to a modified cervical score, were treated with combined clomiphene and conjugated estrogens. The cervical score, the cycle pattern and the pregnancy rate were compared with the results of the previous treatment. The improvement of the cervical score was noted in 74.4% of patients, 6 women became pregnant, and the pregnancy rate related to the number of ovulatory cycles was 13.9%. Criteria for the treatment presented are discussed. PMID- 6267383 TI - Cholecystokinin cholecystography: use of synthetic cholecystokinin octapeptide by different routes of administration. PMID- 6267384 TI - The influence of metronidazole on ultrastructure of rat's liver. PMID- 6267385 TI - Spinal opiate administration for chronic pain: a major advance in therapy. PMID- 6267386 TI - Mayo Lung Project: evaluation of lung cancer screening through December 1979. PMID- 6267387 TI - Surface antigens of BK virus-induced tumor cells. AB - The presence and nature of surface antigens in BKV-induce tumor cells was studied by transplantation rejection experiments, immunofluorescent staining and by complement-mediated cytotoxicity assay. Immunization with an irradiated BKV induced hamster tumor cell line protective syngeneic hamsters not only against a challenge of the same tumor cells but also against a SV40-induced hamster tumor cell line. A control hamster cell line (HDC-22) was also able to protect the hamsters against the later challenge with a BKV-transformed hamster cell line. In addition to species-specific reactions, cross-reactions between BKV-transformed hamster and rat tumor cells were detected by immunofluorescent staining of surface antigens. This reactivity was not due to the Forssman antigen, because the rat cell lines studied were negative by the same method using Forssman antiserum. By the complement-mediated cytolytic antibody assay using [51]Cr labelled tumor cells as targets a "public" antigen was found again in BKV-, SV40- and non-virally transformed hamster and BKV-transformed rat cell lines. PMID- 6267388 TI - [Sturge-Weber-Dimitri syndrome associated with Klippel-Trenaunay syndrome]. AB - A 15 year old boy with congenital angiomatosis showing associated features of Sturge-Weber-Dimitri and Klippel-Trenaunay syndromes is presented by the authors. Some peculiar characteristics are commented in the article. PMID- 6267389 TI - [Scintigraphy and tomography in inflammations and non-malignant tumors in head and neck (author's transl)]. AB - Scintigraphy is a non-invasive technically simple tool for diagnostic in the head and neck. Using nuclides with a short life time the irradiation of the skeleton is less than 1 rd. Scintigraphy in addition to X-ray examination is useful in diagnosis and surveillance of different osteoplastic tumors (like osteoma, osteoplastoma, cementoma, meningioma) and in systemic diseases of the bones (fibrotic dysplasia, Morbus Paget). Concerning inflammatory diseases osteomyelitis is the main indication for scintigraphy, but it is as well usefull in the diagnosis of complications of inflammatory diseases of the sinuses, like mucocelia or non resorbed antibiotics which provoked an inflammatory reaction of the mucosa. There is no indication for scintigraphy regarding its low specificity in common acute or chronic sinusitis. PMID- 6267390 TI - [A modern radiological approach to the diagnosis of juvenile nasopharyngeal angiofibroma (author's transl)]. PMID- 6267391 TI - Seasonal variation in the apparent number of binding sites for 3H-opioid agonists and antagonists. PMID- 6267392 TI - Solubilization of membrane bound opiate receptor from rat brain. PMID- 6267393 TI - Effects of cholera toxin on vasoconstriction and cyclic AMP content of the isolated rabbit ear artery. PMID- 6267394 TI - Increase in nuclear cyclic GMP-dependent protein kinase following partial hepatectomy. PMID- 6267395 TI - Evidence for sedative effects of low doses of morphine in mice involving receptors insensitive to naloxone. PMID- 6267396 TI - Effect of the position of the phenolic group in morphinans on their affinity for opiate receptor binding. PMID- 6267397 TI - Significance of phosphodiesterase in the brain. PMID- 6267398 TI - The actions of naloxazone on the binding and analgesic properties of morphiceptin (NH2Tyr-Pro-Phe-Pro-CONH2), a selective mu-receptor ligand. PMID- 6267400 TI - Interaction of calcium and cyclic nucleotides in thyroliberin-stimulated prolactin release. PMID- 6267399 TI - Behavioral profile of gamma-MSH: relationship with ACTH and beta-endorphin action. PMID- 6267401 TI - Functional and anatomical segregation of hypothalamic opiate receptors involved in prolactin and growth hormone secretion in cynomolgus monkeys. PMID- 6267403 TI - Modification of radiosensitivity of mammalian cells by cyclic nucleotides. PMID- 6267402 TI - Naloxazone irreversibly inhibits the high affinity binding of [125I]D-ala2-D-leu5 enkephalin. PMID- 6267404 TI - Noxious stimulation of animals by brief intense laser induced heat: advantages to pharmacological testing of analgesics. PMID- 6267405 TI - Antagonism of benzodiazepine receptors by beta carbolines. PMID- 6267406 TI - [Proton irradiation of esophageal cancer]. PMID- 6267407 TI - [Ulcer therapy with the gastrin receptor antagonist proglumide. Results of the field study]. PMID- 6267408 TI - [Interdisciplinary total after-care of tumor patients with the aid of the hospital information system]. PMID- 6267409 TI - [Chemotherapy of bronchial cancer]. PMID- 6267410 TI - [Rotavirus in children with acute gastroenteritis]. PMID- 6267411 TI - [Properties of the interfering particles generated by Junin virus in Vero cells]. PMID- 6267412 TI - [Protection induced in guinea pigs by the variant XJ0 of Junin virus]. PMID- 6267413 TI - [Immunologic markers of attenuation in guinea pigs infected with strains or variants of Junin virus]. PMID- 6267414 TI - Histomorphometric study of bone remodeling in hypophosphatemic vitamin D resistant rickets. AB - Static and dynamic histomorphometric parameters were evaluated on undecalcified iliac crest bone biopsies obtained from eight children with untreated hypophosphatemic vitamin D resistant rickets (VDRR) in an attempt to evaluate whether a primary metabolic bone defect contributes to the skeletal disorder observed in that disease. When compared to normal age-matched controls the trabecular calcified bone volume was not decreased and there was no evidence of excessive osteoclastic resorption. Both trabecular and cortical bone envelopes had an excess of osteoid tissue and a decreased extent of the mineralization front. Dual tetracycline labeling revealed a decrease in the osteoblastic calcification rate and a marked prolongation of the mineralization lag time and of the formation period. In the intracortical Haversian system the birthrate of new Basic Multicellular remodeling Units (BMU) was markedly reduced, leading to a marked depression of the bone formation rate at the whole tissue level. The combination of the decreased birthrate of new BMU and the prolonged formation period appears to be characteristic of the disease. These results indicate that abnormal differentiation and function of the osteoblast contribute to the osteomalacic lesion present in VDRR. Defective mineralization and impaired osteoblastic function might be the consequence of the chronic hypophosphatemic state. However, the existence of a primary disorder of the bone cell line cannot be excluded as an explanation of the defective recruitment and function of the bone forming cells. PMID- 6267415 TI - Immunological techniques for studies on the biogenesis of mitochondrial membrane proteins. PMID- 6267416 TI - Three-dimensional reconstruction of membrane protein crystals. PMID- 6267417 TI - Preparing biological samples for stereomicroscopy by the quick-freeze, deep-etch, rotary-replication technique. PMID- 6267418 TI - Plasmid transformation in Bacillus subtilis: effects of insertion of Bacillus subtilis DNA into plasmid pC194. AB - We have constructed a hybrid plasmid pBC1, which consists of plasmid pC194 with an insert of B. subtilis DNA as its HindIII restriction site. This plasmid is stably maintained in B. subtilis. In contrast with pC194, monomeric ccc forms of pBC1 are active in transformation. Transformations with these monomeric molecules of pBC1 have a stringent requirement for recombination proficiency, as defined by recE in the recipient cell. The extent of dependence of the transforming activity of oligomeric pBC1 DNA on the recombination proficiency of the recipient cell decreases with increasing oligomer size. A model of DNA processing during plasmid transformation of B. subtilis is presented. PMID- 6267419 TI - Regulation of methyl beta-galactoside permease activity in pts and crr mutants of Salmonella typhimurium. AB - We have studied the regulation of the synthesis and activity of a major galactose transport system, that of methyl beta-galactoside (MglP), in mutants of Salmonella typhimurium. Two classes of mutation that result in a (partially) defective phosphoenolpyruvate: sugar phosphotransferase system (PTS) interfere with MglP synthesis. pts mutations, which eliminate the general proteins of the PTS Enzyme I and/or HPr and crr mutations, which result in a defective glucose specific factor IIIGlc of the PTS, lead to a low MglP activity, as measured by methyl beta-galactoside transport. In both ptsH,I, and crr mutants the amount of galactose binding protein, one of the components of MglP, is only 5%-20% of that in wild-type cells, as measured with a specific antibody. We conclude that synthesis of MGlP is inhibited in pts and crr mutants. Once the transport system is synthesized, its transport activity is not sensitive to PTS sugars (i.e., no inducer exclusion occurs). The defect in pts and crr mutants with respect to MGlP synthesis can be relieved in two ways: by externally added cyclic adenosine 3',5 monophosphate (cAMP) or by a mutation in the cAMP binding protein. The conclusion that MglP synthesis is dependent on cAMP is supported by the finding that its synthesis is also defective in mutants that lack adenylate cyclase. pts and crr mutations do not affect growth of S. typhimurium on galactose, however, since the synthesis and activity of the other major galactose transport system, the galactose permease (GalP), is not sensitive to these mutations. If the galactose permease is eliminated by mutation, growth of pts and crr mutants on low concentrations of galactose becomes very slow due to inhibited MglP synthesis. Residual growth observed at high galactose concentrations is the result of yet another transport system with low affinity for galactose. PMID- 6267420 TI - Physical and functional mapping of Tn2603, a transposon encoding ampicillin, streptomycin, sulfonamide, and mercury resistance. AB - A map of cleavage sites for restriction endonuclease EcoRI, BamHI, HindIII, and SalI on Tn2603, a transposon encoding resistance to ampicillin, streptomycin, sulfonamide, and mercury, was constructed by an analysis of restriction cleavage patterns of plasmid pMK1.::Tn2603 and its deletion derivative. By cloning the fragments generated from pMK1.::Tn2603 with these restriction endonucleases to a pACYC184 plasmid vehicle, the regions necessary for expression of resistance were located on the restriction cleavage map of Tn2603. Ampicillin, streptomycin, and sulfonamide-resistance genes were mapped in a cluster on the region between the center and the right and the mercury-resistance gene was located to the left of the map. The final functional map of Tn2603 was compared with those of Tn4 and Tn21 and the evolutional relationships between them were discussed. PMID- 6267421 TI - Regulation of the synthesis of adenylate cyclase in Escherichia coli by the cAMP - cAMP receptor protein complex. AB - The synthesis of the adenylate cyclase [ATP pyrophosphatelyase-(cyclizing), E.C. 4.6.1.1.] of Escherichia coli, appears to be regulated negatively by the cAMP receptor protein, CRP. This conclusion is based on a comparison of adenylate cyclase activities measured in vitro with the rates of cAMP synthesis by intact bacteria. The activity of adenylate cyclase, depending on conditions of growth, is also regulated by CRP; this effect, however, is indirect insofar as it is mediated by a protein or proteins under CRP control. PMID- 6267422 TI - Isolation and characterization of prototrophic relaxed mutants of Klebsiella pneumoniae. AB - A new selection procedure has been developed for isolating prototrophic relaxed mutants of Klebsiella pneumoniae. Two mutants were isolated. One of them showed a fully relaxed phenotype, while the other one behaved in a semi-relaxed way. The wild-type strain, as well as the rel mutants exerted similar patterns to their E. coli counterparts in RNA, protein, ppGpp and pppGpp accumulation during amino starvation, carbon source shift-down and nitrogen starvation. Both mutants became stringent after introducing an F'-factor carrying the relA+ allele from Escherichia coli. The relaxed phenotype could be recovered by curing the F' factor. Some of the pleiotropic consequences of rel mutations found in E. coli are present in the Klebsiella mutants also while some of them are absent. The mutants are defective in dinitrogen fixation after the exhaustion of limiting ammonium from the culture medium. However, their merodiploid derivatives, carrying the E. coli relA+ allele, showed the wild-type level of nitrogenase activity under the same conditions. PMID- 6267423 TI - Role of the recF gene of Escherichia coli K-12 in lambda recombination. AB - When Escherichia coli K12(lambda) lysogens are infected with heteroimmune lambda phage, which are unable to replicate, general recombination between phage and prophage depends on the bacterial recF gene. It has been shown that in E. coli K12 postconjugational recombination, the RecF pathway only works with full efficiency if exonuclease I is absent (Clark 1973). However, results presented in this paper indicate that under conditions in which lambda replication is blocked, the recombination pathway dependent on the recF gene is fully active in producing viral recombinants even, if the phage is Red+, in the presence of exonuclease I. In contrast, removal of lambda exonuclease and beta protein requires elimination of exonuclease I for an efficient RecF pathway. It is concluded that the Red system cooperates with the RecF pathway and that this cooperation involves overcoming the inhibitor effects of exonuclease I. In the absence of lambda exonuclease, beta protein stimulates recF-dependent recombination but does not suffice to prevent the negative effect of exonuclease I. In the presence of beta protein, full efficiency of the RecF pathway can be obtained either via cooperation with lambda exonuclease I or, if the viral exonuclease is defective, via inactivation of exonuclease I. Since activity of lambda exonuclease appears necessary to overcome the inhibitory effects of exonuclease I, it is proposed here that lambda exonuclease diverts material from the RecF pathway in a shunt reaction which allows completion of recF-initiated recombinational intermediates via a mechanism insensitive to exonuclease I. When lambda replication is allowed, the Rec system produces viral recombinants mainly via a recF-independent mechanism. However, a major contribution to the RecF pathway to lambda recombination is observed after removal of the Red system and exonuclease. PMID- 6267424 TI - In vivo transcription of Bacillus subtilis bacteriophage SPP1. AB - The temporal program of SPP1 transcription was examined by hybridizing RNA extracted from infected B. subtilis cells, pulse-labelled at various times after infection, to restriction fragments of SPP1 DNA. RNA made early after infection hybridises to contiguous fragments in the left part of the SPP1 molecule, whereas hybridization to fragments in the right part of the chromosome is found late in infection. Viral gene transcription proceeds from right to left on the H-strand throughout the lytic cycle. At late times transcription occurs also from left to right using the L-strand as template. These assignments follow from the established 5'--3' polarity of the complementary (H- and L-) strains of SPP1 DNA and the determination of strand specificity in SPP1 transcription. Early and late transcriptions are also defined physiologically: protein synthesis and phage DNA replication must precede late transcription. PMID- 6267425 TI - Introduction of active enzymes into intact Escherichia coli cells by means of liposomes. Phenotypic suppression of uvr A and pol A mutants. AB - Genetically deficient cells were supplied with the missing enzymes, purified from an independent source. The introduction of exogenous enzymes into the cells was effected by two independent methods: plasmolysis and liposome transformation. The latter procedure yielded a homogenous cell population which had been rescued from the defect even if the molecular weight of the enzyme amounted to 70 KD (Kilodaltons). PMID- 6267426 TI - Cloning, restriction endonuclease mapping and post-transcriptional regulation of rpsA, the structural gene for ribosomal protein S1. AB - Transducing lambda phages have been isolated that carry segments of the Escherichia coli chromosome in the aspC region, 20.5 min on the E. coli map. One of these phages, lambda aspC2, carries rpsA, the structural gene for the ribosomal protein S1. A three kilobase fragment from this phage, cloned into either the plasmid pACYC184 or the plasmid pBR322, was found to express S1. In cells carrying the rpsA gene on the high copy number plasmid pBR322 the rate of rpsA mRNA synthesis was increased 40-fold, whereas the rate of protein S1 synthesis was doubled, in comparison with these rates in an rpsA haploid. PMID- 6267427 TI - Transposon-like structures in the Bacteroides fragilis MLS plasmid plP 410. AB - Homoduplexes of plasmid plP 410 encoding MLS resistance in Bacteroides fragilis strain 92 revealed two "transposon-like" structures: a 17.4 kb loop flanked by 0.75 inverted repeats, and a 4.5 kb loop flanked by 0.2 kb inverted repeats. The large structure is deleted in a derivative plasmid harboured by a MLS susceptible strain. We have also showed that the long and short inverted repeats are structurally related. PMID- 6267428 TI - The isolation and characterization of escherichia coli dnaB::Tn10 insertion mutations. AB - Exploitation of the ability of the ban protein encoded by phage P1 to compensate for dnaB-defective host mutations, allowed the isolation of dnaB::Tn10 insertion mutations. The presence of P1bac prophage was required for survival of dnaB::Tn10 mutants, and such lysogens were cryosensitive. The insertions were shown to map in dnaB by transduction and this was confirmed by complementation analysis. The dnaB::Tn10 (P1bac) strains were non-permissive for lambda growth but did support the growth of lambda-dnaB+ specialized transducing phage. No antigenically active dnaB product could be detected by immunologic assays using either of two methods. In addition, it was shown that the observe cryosensitivity of P1bac suppression was a direct result of reversible inactivation of the ban protein at low temperature. PMID- 6267429 TI - Physical mapping of the genomes of lytic and temperate forms of phage theta. AB - Restriction maps of genomes of the lytic form and diverse temperate mutants of phage theta of Bacillus licheniformis were constructed. Most temperate mutants produced fragmentation patterns identical to that of the parent lytic form, theta c: in other mutants the only detectable change in the map was the deletion of a Bg/II restriction endonuclease site at 46.5% genome length. In the genomes of two other temperate mutants, theta 1 and theta 2, the central part of the genome was replaced by a piece of DNA of equal length, but with a different distribution of restriction sites; the maps of the two mutants failed to reveal any similarity in the location of restriction sites in the inserted DNA. It seems that any alteration comprising the locus around the coordinate 46.5% of the theta c genome, brings about a transition from the lytic to temperate phenotype, indicating the position of a regulatory gene responsible for positive control of phage replication. PMID- 6267430 TI - Analysis of mutations affecting Ty-mediated gene expression in Saccharomyces cerevisiae. AB - Yeast translocatable, Ty, elements can cause constitutive synthesis of the glucose-repressible alcohol dehydrogenase (ADHII) when inserted upstream from the 5' end of the structural gene, ADR2. These insertion mutations, ADR3c, are unstable and give rise to secondary ADHII- mutations. The majority of such mutants, adr3, can be attributed to excision of the insertion sequence, leaving behind a single copy of the delta-sequence which occurs as a direct repeat at the ends of the Ty elements. A few adr3 mutants appear to be generated by DNA rearrangements in the vicinity of the Ty insertion. The occurrence of recessive mutants, tye, which are unlinked to ADR2 indicates that the constitutive expression of ADR2 caused by the Ty insertions requires the function of trans acting genes. These results support the idea that regulation of Ty-linked ADR2 is actively mediated by the insertion sequence and is probably not due to a mere disruption of the wild-type controlling site. PMID- 6267431 TI - Analysis of the reduction in expression of tetracycline resistance determined by transposon Tn10 in the multicopy state. PMID- 6267433 TI - Isolation and physical characterization of streptomycete plasmids. AB - Covalently closed circular DNA was isolated from a strain of Streptomyces coelicolor ATCC 10147 and from a strain of Streptomyces coelicolor subspecies flavus ATCC 19894, using two different methods. The two plasmids were of uniform monomer size: 8.9 kb for pS 10147, the plasmid from S. coelicolor ATCC 10147, and around 125 kb for the plasmid from S. coelicolor ATCC 19894. A restriction enzyme map was constructed for pS 10147, using seven enzymes. Four of the enzymes, (BamHI, Bgl,II, PvuII, and XhoI) cut pS 10147 once while PstI made two cuts. The GC content of this plasmid was calculated to be 72%. The possible utilisation of pS 10147 as a cloning vector in Streptomyces is discussed. PMID- 6267432 TI - The requirement for both DNA polymerase and 5' to 3' exonuclease activities of DNA polymerase I during Tn5 transposition. AB - By assaying transposition of Tn5 from lambda b221 cI857 rex::Tn5 (Berg 1977) in polA-proficient and deficient cells, both the polymerase activity and 5' to 3' exonuclease activity of DNA polymerase I have been shown to be required for transposition. This requirement could not be observed in three other systems in which the transposon donor replicon had existed in the PolA-proficient and deficient cells before the transposition event to be assayed occurred. By analogy to Tn3, this may indicate that the repressor encoded by Tn5 has already been expressed and hence become rate-limiting in the overall transposition process, even PolA-deficient cells still possessing a residual activity. One PolA mutant was found among more than 50 transposition deficient (tnp) mutants isolated by the use of lambda b221 cI857 rex::Tn5. PMID- 6267434 TI - Induction and genetics of two alpha-galactosidase activities in Saccharomyces cerevisiae. AB - The induction of alpha-galactosidase of Saccharomyces cerevisiae was investigated. We have demonstrated the existence of inducible internal and external alpha-galactosidase activities and have studied the relationship between the two alpha-galactosidases by examining a mutant strain which lacks both the internal and external activities. The mutant possesses a mutation in a single locus (mel1-1) which does not affect the synthesis of the other galactose pathway enzymes or the ability of the yeast to grow on media containing only galactose as the carbon source. Genetic studies of the mutant indicate that mel 1-1 is recessive and allelic to the wild tye allele for melibiose fermentation Mel 1. PMID- 6267436 TI - Visna virus synthesized in absence of host-cell division and DNA synthesis. AB - Visna virus is similar to the avian and the murine oncornaviruses. Oncornavirus replication is dependent upon the provirus being integrated into the host cell's DNA but integration and subsequent oncornavirus synthesis is blocked when the host cells are prevented from synthesizing cellular DNA or dividing. The synthesis of visna virus is restricted in vivo and may be dependent upon the host cell's ability to synthesize cellular DNA or divide. Treatment of sheep choroid plexus (SCP) cells with ultraviolet light or with mitomycin C prior to infection irreversibly inhibited plexus (ScP) cells with ultraviolet light or with mitomycin C prior to infection irreversibly inhibited both cell division and cellular nucleic acid synthesis but did not inhibit visna virus synthesis. Similarly, the synthesis of visna virus in cultures of SCP cells which had been prevented from dividing by being deprived of serum and in cultures of SCP cells which were incapable of synthesizing host cell nucleic acids by being treated with miracil D or sodium hexachloroiridate was equivalent to the synthesis of visna virus in cultures of SCP cells which were allowed to both synthesize cellular nucleic acids and divide. The synthesis of visna virus in the presence of ethidium bromide further demonstrated that integration of the visna provirus into the host cell's DNA is not required for visna virus synthesis to occur. PMID- 6267435 TI - DNA replication intermediates synthesized by lysates of dnaB, dnaG and dnaB dnaG mutants in vitro. AB - Isogenic dnaB, dnaG, and dnaB dnaG mutants were constructed and used as extracts in the cellophane-disc in vitro DNA replication system. The increased proportion of 5S DNA characteristics of the dnab extract and the lack of Okazaki piece synthesis characteristic of the dnaG extract were both apparent in analysis of the dnaB dnaG mutant extract reaction. A hypothetical scheme to explain these results and those of others is presented. PMID- 6267437 TI - [ACTH measurement in the hypophysis after adrenalectomy and adrenal cortex hormone therapy by means of microphotometry and radioimmunoassay method (author's transl)]. AB - In experiments after adrenalectomy and adrenal cortex hormone therapy the quantity of ACTH was ascertained in the hypophysis of cats by methods of microphotometry and radioimmunoassay. The deviation of increased or decreased amounts was studied in acute as well as in chronic physiological conditions of the cats. The different methods to measure the quantities are equally identifying the physiological conditions. PMID- 6267438 TI - New drugs for enteric gram-negative bacillary meningitis in adults. PMID- 6267439 TI - Fulminant lung metastases from cancer of the breast. AB - Fulminant, rapidly fatal pulmonary metastatic disease occurred in two breast cancer patients. The radiologic appearance in both suggested infection. Immunosuppression may have contributed to this overwhelming illness. Attempts to obtain a tissue diagnosis are warranted in cancer patients if acute pulmonary infiltrates do not respond to appropriate antibiotics. PMID- 6267440 TI - Phase II evaluation of mitomycin C (MMC) in children with refractory solid tumors using the single high-intermittent-dose schedule. AB - Nine evaluable patients with refractory solid tumors received mitomycin C as a single intravenous injection at a dose of 20 mg/m2 at 6- to 8-week intervals. Toxicity was tolerable. One patient with Wilms' tumor had a transient decrease in liver size. Pharmacokinetic data on three patients have suggested that the disposition of mitomycin C were comparable to those obtained in adults. PMID- 6267442 TI - Enterovirus-associated illness--Florida, Arizona, Tennessee, 1981. PMID- 6267441 TI - [The BM test and lysosomal enzyme in the meconium in neonatal screening of cystic fibrosis]. PMID- 6267443 TI - Interaction of diazosulfanilic acid and the opiate receptor: inhibition of specific binding to synaptic membranes and labeling of a membrane lipid stereospecifically protected by opioids. PMID- 6267444 TI - Mathematical analysis of the kinetics of competitive inhibition in neurotransmitter receptor binding assays. PMID- 6267445 TI - Conformational analysis of nonsteroidal estrogens: The effect of conformer populations on the binding affinity of meso- and dl-hexestrol to the estrogen receptor. PMID- 6267447 TI - The effect of tienilic acid on Na+ and K+ transport in human red cells. PMID- 6267446 TI - Regulation of the rat pituitary gonadotropin-releasing hormone receptor. PMID- 6267448 TI - Alternative explanation for the apparent "two-step" binding kinetics of high affinity racemic antagonist radioligands. PMID- 6267449 TI - Immune complex binding induces lateral lipid re-ordering in rat macrophage plasma membrane. PMID- 6267450 TI - Spin-label studies of hapten combining sites in anti-p-azobenzoate antibodies. PMID- 6267451 TI - [Determination of the copper content of liver tissue from paraffin-imbedded samples by electron spin resonance spectroscopy]. AB - The Electron Spin Resonance spectrum of human liver specimens embedded in paraffin was investigated. An easily registrable mark could be seen in the g 2.05 range of the spectrum. A correlation was detected between the amplitude of this mark of the embedded specimens and the copper content of them measured by a flame ionic-absorptive technique. Authors assume that ESR-spectroscopy is a useful tool for the estimation of the copper content of a specimen, it does interfere with the following histological processing of it. Sources of errors are shortly discussed. PMID- 6267452 TI - [Electron spin resonance study of melanin in paraffin-imbedded ocular melanoma specimens]. AB - The Electron Spin Resonance (ESP) spectrum of ocular melanomas embedded in paraffin was studied. In the g approximately 2.003 range of the spectrum a mark of a free radical was detected. The correlation between the amplitude of the latter and the number of melanin granules in sections was studied. Considering the positive correlation revealed, authors believe, that ESR spectroscopy is a suitable tool for detecting melanin in paraffin embedded specimens. As an effect of oxidation or reduction melanin turns pale, however this phenomenon is not in tight connection with the decrease of the amplitude of the free-radical-mark. Very seldom different types of spectrum (peroxide, cupric ion) may appear, so it is reasonable to study large number of specimens. PMID- 6267453 TI - [Granulofilamentous intranuclear bodies detected by ultrastructural studies in lichen planus and psoriasis]. AB - Based on ultrastructural studies and findings reported in the literature occurrence, frequency, morphological and structural pattern of intranuclear inclusions in lichen ruber planus and psoriasis were analyzed and compared with other structures. It was concluded that granulofilamentar bodies in lichen and psoriasis are not specific structures. They develop as an effect of physiologic and pathologic (hyper) activating factors and may be reversible. Granulofilamentar structures seem to represent separate group of intranuclear bodies. To clear up their features further investigations are needed. PMID- 6267454 TI - The effect of cell irradiation on mutation in ultraviolet-irradiated and intact simian virus 40. AB - The induction of phenotypic wild-type revertants in the progeny of an unirradiated or UV-irradiated temperature-sensitive late mutant of simian virus 40 was studied after low multiplicity passages in normal or UV-irradiated confluent monkey kidney cells. The production of wild-type revertants in the progeny of undamaged tsBC245 was followed by infecting the cells at distinct times after irradiation of the cells. Mutation frequencies reached a maximum when infection was delayed for 3--4 days after irradiation of the host cells, and declined gradually thereafter. Virus grown in unirradiated cells did not show such an alteration in mutation frequency. The temporarily higher mutation frequency of virus in UV-pretreated cells is due to a transient mutator activity operating in these cells rather than to an increased number of replications performed in UV-irradiated cells. A similar time course was found for the reactivation of UV-damaged SV40. This might suggest that reactivation and mutagenesis are manifestations of the same process. The yield of mutants due to irradiation of the virus alone was enhanced when infection was delayed for some days after the cells reached confluency; UV pretreatment of the host cells did not enhance the level of mutation obtained by UV irradiation of the virus. PMID- 6267455 TI - Strand cleavage at psoralen adducts and pyrimidine dimers in DNA caused by interaction between semi-purified uvr+ gene products from Escherichia coli. AB - Partially purified extracts of Escherichia coli containing either uvrA+ or a mixture of uvrB+ and uvrC+ gene products were tested for an endonuclease activity on DNA treated with 8-methoxypsoralen plus 360-nm light. Neither of these fractions was active alone. The combined fractions, however, caused extensive strand cleavage of the psoralen-treated DNA. The endonuclease activity was dependent upon addition of ATP and Mg2+ to the reaction mixtures, and hence appeared similar to the UV-endonuclease activity previously shown to be reconstituted from the same fractions. It is concluded that the uvr+ gene products in these fractions interact to cause breakage of both psoralen-treated and UV-irradiated DNA. An examination of the dose-dependence relationship of the break formation in psoralen-treated DNA revealed that the enzyme acts upon psoralen mono-adducts. By varying the experimental conditions to increase the ratio of interstrand cross-links to mono-adducts it was found that the enzyme also acts upon cross-links, but with lower efficiency than for mono-adducts. Further studies of break formation in UV-irradiated DNA showed that elimination of pyrimidine dimers by treatment with photoreactivating enzyme in the light resulted in a loss of endonuclease-sensitive sites. This shows directly that pyrimidine dimers are the lesions recognized by the complemented uvr+ gene products in UV-irradiated DNA. For comparison, another endonuclease acting at pyrimidine dimers in DNA, the Micrococcus luteus UV-endonuclease, was also tested with psoralen-treated DNA, but no activity was observed. This and other data indicate that the repair endonuclease encoded by the uvr+ genes in E. coli is basically different from the other dimer-specific endonucleases previously characterized. PMID- 6267456 TI - Sensitive determination of pyrimidine dimers in DNA of UV-irradiated mammalian cells. Introduction of T4 endonuclease V into frozen and thawed cells. AB - Endonuclease V from E. coli infected with phage T4 was used to evaluate the frequency and the removal of pyrimidine dimers from DNA in cultured mammalian cells. Cellular membranes were made permeable to the enzyme by two cycles of rapid freezing and thawing. The number of endonuclease-sensitive sites in DNA was assayed by sedimentation in alkaline sucrose gradients upon which the cells were lysed directly. Comparison of the frequency of endonuclease-sensitive sites with the frequency of pyrimidine dimers determined by chromatographic analysis of hydrolysed DNA indicated that about 50% of the dimers in the permeabilized cells were substrates for T4 endonuclease V. This was confirmed by observation that when DNA treated with the enzyme in situ was purified, it contained the expected additional number of endonuclease-sensitive sites if again treated with the enzyme. The percentage of pyrimidine dimers recognized by T4 endonuclease V was enhanced to nearly 100% by exposing the permeabilized cells to 2 M NaCl before the enzyme was introduced. This method allowed the measurement of frequencies of endonuclease-sensitive sites after doses of UV irradiation at low as 0.5 J/m2. Loss of endonuclease sites from cellular DNA was observed during post-irradiation incubation of V79 Chinese hamster cells and several human cell strains. A comparison of the results obtained in human cells with or without the high-salt exposure before endonuclease treatment suggested that the dimers recognized under low-salt conditions may be removed slightly faster than those recognized only after high-salt exposure. PMID- 6267457 TI - Alteration of plasmid DNA-mediated transformation and mutation induced by covalent binding of benzo[alpha]pyrene-7,8-dihydrodiol-9,10-oxide in Escherichia coli. AB - Plasmid-mediated transformation and mutagenesis induced by (+/-)-trans benzo[alpha]pyrene-7,8-dihydrodiol-9,10-oxide (BP-DEI) in recipient Escherichia coli (E. coli) have been studied. Because plasmid DNA is used, the system is entirely free from direct toxic effects of BP-DEI on the recipient cells. Plasmid pK0482 DNA, which has two dominant genes, beta-lactamase (amp-r) and galactokinase (galK) was modified with BP-DEI prior to its transformation of E. coli N99, AB1157, AB2463(recA-) and AB1886(uvrA-). Transformants were selected by ampicillin resistance and mutations were analyzed simultaneously by the altered expression of the galK gene. (1) Approx. 3 molecules of BP-DEI per molecule of pK0482 DNA decreased the transformation efficiency to 37% in AB1157 and the mutation frequency in this strain was proportional to the amount of BP-DEI covalently bound to pK0482 DNA. (2) In Ab1886(uvrA-) a 37% transformation efficiency was produced by only 1 molecule of BP-DEI per molecule of pK0482 DNA, and the mutation frequency in this strain was higher than in AB1157. (3) In AB2463(recA-), the transformation efficiency was similar to that obtained with AB1157, but mutagenesis was clearly suppressed. (4) Polyacrylamide gel patterns of restriction digests of the pK0482 mutated at the galK gene were indistinguishable from those of the unmutated plasmid DNA. PMID- 6267458 TI - Use of nitrous acid-dependent decrease in mutagenicity as an indication of the presence of mutagenic primary aromatic amines. Non-specific reactions with phenols and benzo[alpha]pyrene. AB - Treatment of mutagenic primary aromatic amines with nitrous acid is known to decrease their mutagenicity. We examined some factors concerning the validity of using decreases in mutagenicity due to nitrous acid treatment as an indication of the presence of mutagenic primary aromatic amines in complex mixtures. We found that treatment of benzo[alpha]pyrene with nitrous acid for the extended periods of time previously employed leads to formation of three nitrobenzo[alpha]pyrene isomers. Some of the isomers are direct-acting mutagens for S. typhimurium with considerably greater mutagenicity than benzo[alpha]pyrene isomers. In attempts to minimize reaction of chemicals other than aromatic amines, we found that only very brief reaction periods are required for complete reaction of nitrous acid with representative aromatic amines, essentially eliminating their mutagenicity. During such brief reaction periods modification of benzo[alpha]pyrene is negligible, but phenols react readily. Chromatographic analysis indicated that reaction of nitrous acid with aromatic amines leads to the formation of families of products, thereby increasing the complexity of the mixtures in which the amines may occur. Thus, experiments examining the effects of nitrous acid on the mutagenic activity of complex mixtures must be carefully designed, and the results must be interpreted cautiously. PMID- 6267459 TI - Influence of mutations at the rep gene on survival of Escherichia coli following ultraviolet light irradiation or 8-methoxypsoralen photosensitization: evidence for a recA+ rep+-dependent pathway for repair of DNA crosslinks. AB - Bacteria mutant at the rep gene (specifying a DNA-unwinding enzyme) were slightly more sensitive than rep+ bacteria to far ultraviolet light (ca. 254 nm; (FUV) and to monofunctional psoralen photoproducts produced with near ultraviolet light (ca. 360 nm; NUV). The enhanced sensitivity was shown in uvrA excision-deficient bacteria but not in those carrying the recA mutation. It is concluded that the rep unwinding enzyme has a small promoting effect on post-replication recombination repair. Rep- bacteria were rather more sensitive to the DNA cross linking action f 8-methoxypsoralen (8-MOP) and NUV. This effect also was found in uvrA but not in recA bacteria. A cross-link repair pathway, dependent on both the recA+ and rep+ genes, therefore exists in addition to the pathway which depends upon the uvrAB endonuclease. Various lines of evidence suggest that the pathway operates at or after DNA replication. Exposure of rep+ bacteria to 8-MOP plus NUV did not induce any activity capable of repairing psoralen cross-links in infecting lambda phage. A possible model involving removal of the cross-link by glycosylase action at the replication fork is proposed. PMID- 6267460 TI - Absence of mutagenicity of phloxine and phloxine B in Escherichia coli and in Salmonella typhimurium. PMID- 6267461 TI - The induction of chromosome aberrations in Notobranchius rachowi (Pisces: Cyprinodontidae) after treatment with ethyl methanesuphonate or Benzo[a]pyrene. PMID- 6267463 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 37-1981. PMID- 6267462 TI - Hemoglobin H disease and mental retardation: a new syndrome or a remarkable coincidence? AB - Each of three families of northern European origin contains a mentally retarded son with hemoglobin H (Hb H) disease. One parent is a carrier of mild alpha thalassemia and the other is normal, suggesting that this form of Hb H disease results from the interaction between an inherited defect of alpha-chain production and one member of the pair in chromosome 16 and a new mutation on the other. Restriction-enzyme analysis indicated that the new mutation was not the same in the other three patients, and demonstrated at least two hitherto undescribed lesions involving the alpha-globin gene cluster. Unless the association between the Hb H disease and mental retardation is fortuitous, the new mutations may also be related to the development changes in these children. Since the mutations only came to light because there was concurrent inheritance of an additional alpha-thalassemia determinant, this type of mutation of chromosome 16 may have been overlooked in other mentally retarded patients. PMID- 6267464 TI - Reversible inhibition of testicular steroidogenesis and spermatogenesis by a potent gonadotropin-releasing hormone agonist in normal men: an approach toward the development of a male contraceptive. AB - We studied the antifertility effects of a potent gonadotropin-releasing hormone agonist, D-Trp6-Pro9-N-ethylamide-LHRH (LHRHA) in eight normal men, who received daily subcutaneous injections for six to 10 weeks. Plasma testosterone levels fell substantially in all eight. Plasma 17-hydroxyprogesterone and serum estradiol-17 beta levels decreased concordantly with plasma testosterone. Impotence developed in five men between the sixth and seventh weeks of treatment, with resolution in each case within two weeks of stopping treatment. Serum gonadotropin levels also fell during treatment, briefly rebounding above basal levels when therapy ended. Sperm density and motility fell t a nadir during the seventh to 18th week after therapy. In six subjects sperm levels fell to 6 X 10(6) sperm per milliliter or less, and in the other two they decreased 70 and 86 per cent below basal mean values. Sperm density returned to pretreatment levels in all men during the 10-to-14-week recovery period. These results are consistent with LHRHA-induced pituitary "desensitization" but do not exclude a direct inhibitory effect of LHRHA on testicular steroidogenesis and spermatogenesis. PMID- 6267465 TI - Development of a male contraceptive--a beginning. PMID- 6267466 TI - Sensitivity of gram-negative organisms to cefotaxime. PMID- 6267468 TI - Aflatoxins, hepatitis B virus, and hepatocellular carcinoma. PMID- 6267467 TI - Nuclear cardiology (first of two parts). PMID- 6267469 TI - Current status of preclinical research on disposition, pharmacokinetics, and metabolism of naltrexone. PMID- 6267470 TI - Treatment of osteoarthritis of the spine and herpetic neuralgia at the Pain Center, Mount Sinai Medical Center. AB - This presentation will briefly describe the operation of this Pain Center and discuss the two chronic pain problems most commonly seen in our geriatric population: osteoarthritis of the spine and herpetic neuralgia. Osteoarthritis of the spine is the most common radiologic finding in middle-aged and older people with low back pain. 32% of our patients have this diagnosis as the basis of their chronic pain. The typical patient is 72 years old and has a past pain history which includes several years of back pain treated by various physicians with anti inflammatory agents and analgesics to no avail. Past history of surgery and drug abuse is rare; however, depression is common. Therapy at the Pain Center is primarily the use of an exercise program and epidural and/or subarachnoid steroids. At the last visit, approximately 70% of the patients have had significant improvement. Herpetic neuralgia is found in 13% of all patients seen at the Mount Sinai Medical Center Pain Center. Our typical patient is 73 years old and has had PHN for 10 months unrelieved by various topical and oral medications. Although rarely is there a history of drug abuse or surgery, extreme depression is common. If the duration of the neuralgia is less than one year, 85% of patients get significant or complete relief from the use of sympathetic nerve blocks and/or the subcutaneous infiltration of steroids and local anesthetic. Once the PHN has been present for more than one year, only 55% of the patients are improved. PMID- 6267471 TI - White or brown? PMID- 6267472 TI - Regular patchy distribution of cytochrome oxidase staining in primary visual cortex of macaque monkey. PMID- 6267473 TI - Transposable elements and proviruses. PMID- 6267474 TI - Membrane manoeuvres in Marseille. PMID- 6267475 TI - Mycoplasmas induce collagenase in BALB/c 3T3 cells. PMID- 6267476 TI - Two distinct candidate transforming genes of lymphoid leukosis virus-induced neoplasms. PMID- 6267477 TI - Sequence specificity of methylation in higher plant DNA. PMID- 6267478 TI - Conditions required for the inhibitory feedback loop in noradrenergic transmission. PMID- 6267479 TI - Inhibition of SV40 replication in simian cells by specific pBR322 DNA sequences. PMID- 6267480 TI - Consistent molecular genetic variation in human gastrointestinal carcinomas. PMID- 6267481 TI - Ca channel inactivation by intracellular Ca injection into Helix neurones. PMID- 6267482 TI - Random diets. PMID- 6267484 TI - Swine vesicular disease viruses isolated from healthy pigs in non-epizootic period. II. Vesicular formation and virus multiplication in experimentally inoculated pigs. AB - An infection experiment was carried out on pigs with swine vesicular disease virus isolated from healthy pigs (SVDV-H). Inoculation was done by two routes, intradermal in the coronary band of the foot and oral. Observation was made on the formation of vesicles and their spread, the virus contents of serum, swab of the oral cavity, and feces, the vicissitude of neutralizing antibody titers, and the distribution of virus in the body. From its results the pathogenicity of virus was judged. In the pigs inoculated intradermally there was a difference in the extension of the area involved in vesicular formation between any two strains of virus. That is, vesicular formation was restricted to the site of inoculation, involved the site of inoculation and the sole of the hoof, or spread over the oral and nasal regions. In every pig, however, vesicles developed only for 2 approximately 5 days after inoculation. After that, repair progressed rapidly. Some strains caused viremia, which was mild. The virus was detected from the site of vesicular formation, but not from any organ. Neutralizing antibody began to be detected 3 days after inoculation. Its titer reached a plateau about 10 days later. In the pigs inoculated perorally, no vesicles were formed. The virus was only detected from the tonsils and the intestinal contents. These findings made it clear that SVDV-H was less pathogenic than swine vesicular disease virus isolated from diseased pigs. PMID- 6267483 TI - [Apatite as micro-calcification in mammary carcinoma]. PMID- 6267485 TI - Crystal formation of swine vesicular disease virus in porcine kidney cells (IB-RS 2 cells). AB - Crystal formation of swine vesicular disease virus (SVDV) in IB-RS-2 cells was studied by electron microscopy. Cells were harvested 0, 3, 3.5, 4, 4.5, 5, 6 and 7 hours after inoculation. Crystalline arrays of SVDV was first observed in the cytoplasm of a few cells 4.5 hours after inoculation. In the cytoplasm of many cells harvested at 5 hours, 1 to 3 crystalline arrays of SVDV were observed. After that, a small number of cells had crystalline arrays in the cytoplasm. The cells with crystalline arrays were rich in ribosome and polysome with dilated mitochondria and many tiny vesicles. An individual virus particle was ca. 18 nm in diameter, and the center-to-center space ca. 22 nm. Crystalline arrays varied in size depending on the plane of section. PMID- 6267486 TI - Alkylxanthines elevate hippocampal excitability. Evidence for a role of endogenous adenosine. AB - The effects of four xanthines (theophylline, 8-phenyltheophylline, isobutylmethylxanthine (IBMX), and 7-benzyl-IBMX) were studied in the hippocampal slice in vitro. These agents increased the excitability of this preparation with 8-phenyltheophylline being the most potent, 7-benzyl-IBMX the least potent, and theophylline and IBMX having intermediate potencies. A similar rank order was observed in terms of the potencies of these xanthines in antagonizing a) electrophysiological responses to adenosine, and b) adenosine-stimulated cyclic AMP formation. These results indicate that the excitatory actions of xanthines in the vivo hippocampus can be most easily explained on the basis of their ability to block adenosine's actions; the CNS excitatory actions of these drugs in vivo may depend upon a similar mechanism of action. PMID- 6267487 TI - [Familial occurrence of glomus tumors; clinical and genetic aspects]. PMID- 6267488 TI - [Differential diagnosis problems during the 1978 polio epidemic]. PMID- 6267489 TI - [Socio-medical problems in neurology (author's transl)]. PMID- 6267491 TI - Norepinephrine uptake in aging adrenergic nerve terminals. AB - Norepinephrine (NE) uptake has been studied in the adult (3-6 months) and aging (5 yr) chick iris, in which there is a discrete population of norepinephrine containing nerve terminals. although total accumulation of 3H-NE in the iris does not change with age, there is a decline in Na+-dependence, temperature sensitivity, ouabain-and inhibitor -sensitivity of uptake. The results indicate either a loss of active, carrier-mediated NE uptake during aging, or a change in the biochemical and pharmacological characteristics of this uptake. changes in the composition of the organ and in the sites of accumulation of NE are considered. PMID- 6267490 TI - Prolactin status in experimentally induced acute renal failure in the rat. AB - Serum prolactin levels were elevated in male Sprague-Dawley rats with acute renal failure induced by glycerol administration. Specific prolactin binding to kidney membrane preparations was reduced in glycerol and antirat glomerular basement membrane serum-treated rats, after morphological and biochemical acute renal failure was evident. Extensive tubular damage after glycerol administration may account for loss of renal binding, since prolactin receptors are mainly tubular in localization. However, the predominant glomerulopathy, with less severe tubular lesions, after antirat glomerular basement membrane serum suggests that reduced renal prolactin binding in these animals is unlikely to be due to tubular destruction alone. Thus, alterations in prolactin status occur with development of experimentally induced acute renal failure and suggest altered renal responsiveness to prolactin in uraemia. PMID- 6267492 TI - Senescent pathology of cerebellum: Purkinje neurons and their parallel fiber afferents. AB - Two groups of naive male Sprague-Dawley rats, 5-7 and 24-26 months of age, were anesthetized with continuous intraperitoneal infusion of 4% chloral hydrate. Stimulation of the cerebellar vermis molecular layer permitted measurements of 12 different electrophysiological properties of parallel fiber Purkinje cell circuitry: parallel fiber conduction velocity, refractory period, threshold, and current dependent volley amplitude; slow negative wave threshold and current dependent amplitude; Purkinje cell activation threshold, latency, and current dependent spike driving; and Purkinje cell inhibitory threshold, latency, and current dependent duration of inhibition. Old subjects demonstrated deficits on all parameters except Purkinje cell inhibitory threshold. The relevance of these findings to our previous research on senescent changes in cell number, lipofuscin deposition, and spontaneous firing of Purkinje cells is discussed. PMID- 6267493 TI - Effect of age on sensitivity to pain and brain opiate receptors. AB - Age-related differences in sensitivity to pain as induced by heat and electrical shock were seen among groups of rats; 2-3, 6-12, and 24 months of age. These are differences were at least partially obliterated by naloxone treatment, suggesting that changes may occur in the endogenous opioid system during aging. In contrast to higher pain thresholds in older animals, however, are decreased concentrations of opiate receptors in the frontal poles, striatum and hippocampus. Anterior cortex and amygdala exhibit a trend toward decreased concentration with increased age, but this is not significant. No age changes in binding affinity occur in any of the brain regions examined. Possible explanations for the apparent discrepancy between altered receptors and response include: higher endogenous opioid levels in aged rats, mediation of pain sensitivity by brain regions other than those examined, difficulties inherent in attempting to localize age changes at a single step in such a complex process, and possibly differential spinal pathways mediating the various types of pain. PMID- 6267494 TI - Protein synthesis by astrocytes in primary cultures. AB - Protein synthesis, measured as leucine incorporation into acid-precipitable proteins, was determined in astrocytes in primary cultures obtained from the cerebral hemispheres of newborn mice. As can be expected for eucaryotic, ribosomal protein synthesis, the incorporation was almost completely inhibited by cycloheximide (0.01 mM), but unaffected by chloramphenicol (0.03 mM). The rate of synthesis, measured during exposure to a high (0.8 mM) concentration of leucine was 5.4 nmol/hr/mg protein in mature (i.e., at least 4-week-old) cultures. This value is at least twice as high as the protein synthesis rates reported for the adult brain in vivo, suggesting that a very considerable part of the protein synthesis in the adult brain may take place in astrocytes. The molecular weight distribution of the synthesized proteins was determined by polyacrylamide gel electrophoresis, demonstrating synthesis of at least 50 different polypeptides, ranging in molecular weight between 190,000 and 27,000 daltons. The pattern of the synthesized proteins underwent considerable alteration with age in young cultures in which the total content of protein was still increasing, but it was remarkably stable after the age of two weeks. Exposure to dibutyryl cyclic AMP, which is known to alter morphology, content of glial fibrillary acidic protein (GFA), and activities of certain enzymes in the cultures in the cultured astrocytes, caused marked alterations in the pattern of the synthesized proteins. PMID- 6267495 TI - Effect of exogenous gangliosides on synaptosomal membrane ATPase activity. AB - Changes in the activity of (Na+, K+)-ATPase of synaptosomal membranes induced by exogenous gangliosides were studied. Depending on the ganglioside-protein ratio, the enzyme activity was finally reduced to 40% when the ratio was about 1. By analysis of the reaction kinetics the effect was characterized as a noncompetitive inhibition. Moreover the ganglioside effect was clearly dependent on the incubation temperature. Since exogenous gangliosides thereby caused a shifting in the optimum temperature of (Na+, K+)-ATPase, the effect is discussed in terms of changes of the membrane properties. In preincubation experiments it was revealed that the interaction of the glycolipids with synaptosomal membranes itself was temperature dependent and enhanced by ATP. It is suggested that ganglioside micelles might have been incorporated by the membranes in a way comparable to a fusion process. PMID- 6267496 TI - [Lymphocyte subpopulations in the cerebrospinal fluid and peripheral blood in lymphocytic meningitis]. AB - Lymphocyte subpopulations were evaluated in the cerebrospinal fluid and peripheral blood in 22 patients in the initial stage of aseptic meningitis and during convalescence. In the acute stage of the disease the proportion of lymphocytes T, including their active forms, was increased, during convalescence a further significant rise was observed in the subpopulation of lymphocytes T with a fall of the proportion of lymphocytes bearing the high "avid" Fc IgG receptor. In patients with acute meningitis and during convalescence a rise was observed in the proportion of lymphocytes T in the peripheral blood. In the acute stage of the disease the number of lymphocytes with a high binding ability of the Fc receptor was decreased. Changes in lymphocytes subpopulations in aseptic meningitis suggest mobilization of lymphocytes engaged in the cell-mediated immune response. PMID- 6267497 TI - [Case of recurrent encephalomyeloradiculomeningitis after coxsackievirus infection]. AB - The authors report a case of recurring encephalomyeloradiculomeningitis after Coxsackie B4 virus infection in a boy aged 14 years. The peculiar course of the disease is interpreted as an expression of the neuroallergic process caused by preceding viral infection. PMID- 6267498 TI - [Embryonal hemangioma and adenoma of the pituitary gland in a patient. Case report]. AB - The authors describe a 54-year-old woman treated surgically 28 years earlier for embryonal haemangioma of the cerebellum and admitted with signs of hypophyseal tumour. Radiological examinations confirmed this suspicion and the patient was treated surgically from the approach through the nose and sphenoidal bone. The previous disease and intraoperative observation suggested the possibility of embryonal angioma in the sella but histological examination demonstrated that the tumour was a chromophobe adenoma. PMID- 6267499 TI - Importance of norepinephrine alpha 2-receptor activation for morphine-induced rat growth hormone secretion. AB - The normal pulsatile secretion of rat growth hormone (rGH) requires intact function in monoaminergic neurons. The importance of norepinephrine (NE) for the secretion is well documented, while the roles of dopamine (DA) and 5 hydroxytryptamine (5-HT) are still a matter of controversy. Morphine, as well as endogenous opioid peptides, are known to stimulate the secretion of GH. Whether the opiate-induced GH release is dependent on monoamines was investigated in the present study. Administration of morphine (10 mg/kg) resulted within 30 min in elevations of plasma rGH exceeding 40 ng/ml. This effect was almost completely antagonized by reserpine (10 mg/kg), given 5 h before morphine and partially antagonized by reserpine (2 mg/kg) administered 25 h before morphine. Administration of tetrabenazine (75 mg/kg) protects monoamine granules from irreversible destruction and counteracted the morphine antagonistic effects of reserpine (2 mg/dg) on rGH secretion indicating that the latter effect is due to blockade of monoaminergic neurotransmission. Pretreatment with either haloperidol (1 mg/kg), p-chlorophenylalanine (PCPA) (300 mg/kg x III) or phenoxybenzamine (10 mg/kg) did not reduce the effect of morphine on rGH release whereas yohimbine (3 mg/kg) effectively prevented it. In reserpine-pretreated animals administration of clonidine (0.5 mg/kg) potentiated the GH releasing effect of morphine. These results indicate that morphine-induced GH release is dependent on activation of postsynaptic NE receptors of the alpha 2-subtype. PMID- 6267500 TI - Nemaline myopathy and a mitochondrial neuromuscular disorder in one family. AB - A family composed of parents and four children is reported. Two brothers presented from early infancy with hypotonia and non-progressive weakness. Muscle biopsy in both revealed numerous typical nemaline rods. The father, suffering from backache, had a slow MNCV of both common peroneal nerves. His muscle revealed variation in fiber size, splitting, type 1 atrophy and numerous pleomorphic mitochondria with crystalline inclusions. The mother's muscle showed type 2 atrophy, foci of myofibrillar degeneration, and lipofuscin bodies. In a 12 year-old daughter and a 5-year-old son the muscle revealed an excess of small, bizarre mitochondria and lipid droplets. The coexistence of nemaline myopathy and a mitochondrial neuromuscular disorder in one family has never been reported in the literature. It might be a coincidence of two rare muscle disorders in one family, or it might be the polymorphic expression of a single etiological factor causing a defect in protein synthesis. PMID- 6267501 TI - Congenital myopathy with cytoplasmic bodies. AB - Since early infancy, a 15-year-old girl had suffered from an apparently static neuromuscular disorder that chiefly afflicted her proximal muscles but did not spare her distal ones. Her CPK values had repeatedly been mildly elevated and her electromyogram had been considered "myopathic". There were no similar neuromuscular disorders in the family. Quadriceps muscle biopsy showed a type I myofiber predominance of 96%, this girl's muscle disease represented "congenital myopathy with cytoplasmic bodies" as cytoplasmic bodies were recently reported in other sporadic and hereditary neuromuscular disorders of unknown origin. PMID- 6267502 TI - The interaction between barbiturate anaesthetics and excitatory amino acid responses on cat spinal neurones. PMID- 6267503 TI - The participation of substantia nigra zona compacta and zona reticulata neurons in morphine suppression of caudate spontaneous neuronal activities in the rat. PMID- 6267504 TI - Central depressant effects of caerulein and cholecystokinin octapeptide (CCK-8) differ from those of diazepam and haloperidol. PMID- 6267505 TI - Circadian variations in the effects of cyclic nucleotides on the thermoregulatory behaviour of a teleost fish. PMID- 6267507 TI - Homocysteine-induced seizures in the mouse cerebral cortex after propranolol pretreatment. Lack of correlation between cyclic adenosine monophosphate levels and phosphorylase activation. PMID- 6267506 TI - Enhancement of ethanol-induced sedation and hypothermia by centrally administered neurotensin, beta-endorphin and bombesin. PMID- 6267509 TI - Influences of precerebellar systems triggering movement on single cells of the interpositus nucleus of the cat. PMID- 6267508 TI - The permeability of the transducer membrane of the crayfish stretch receptor to calcium and other divalent cations. PMID- 6267510 TI - Decrease in choline acetyltransferase activity in the red nucleus of the cat after cerebellar lesion. PMID- 6267511 TI - Comparison of beta-adrenoceptors in bovine intracerebral microvessels and cerebral grey matter by [3H]dihydroalprenolol binding. PMID- 6267512 TI - Regional segregation of neurons responding to quickly adapting, slowly adapting, deep and Pacinian receptors within thalamic ventroposterior lateral and ventroposterior inferior nuclei in the squirrel monkey (Saimiri sciureus). PMID- 6267513 TI - Arsenic neuropathy. PMID- 6267514 TI - Multisystem neuronal degeneration, hepatosplenomegaly, and adrenocortical deficiency associated with reduced tissue arachidonic acid. PMID- 6267515 TI - Canine viruses and multiple sclerosis. AB - Serum and cerebrospinal fluid from multiple sclerosis (MS) patients and control subjects were tested and compared for presence and titer of neutralizing antibody against the most common canine viruses. Canine viruses included canine distemper virus (CDV), canine adenovirus 1 (CAV-1), canine parainfluenza virus (CPIV), canine herpesvirus (CHV), canine coronavirus (CCV), and canine parvovirus (CPV). Neutralizing titers against measles virus (MV) and human adenovirus 8 (HA8) were also tested. Significantly elevated (p less than 0.05) antibody levels in sera from MS patients were found only against MV and CDV, but this depended upon the study population and the method of evaluation. The CDV-neutralizing component in serum could be absorbed on MV-infected cells. Results of this study failed to establish a link between canine viruses and MS. PMID- 6267516 TI - Measles antibody titers in multiple sclerosis patients and HLA-matched and unmatched siblings. AB - Antibody titers to measles, cytomegalovirus, and herpesviruses 1 and 2 were compared for siblings of multiple sclerosis (MS) patients sharing two, one, and no histocompatibility antigen haplotypes with the case. Significant differences were observed only for measles. Titers were significantly lower in siblings sharing no haplotypes with the case. Within case-sibling pairs, the presence of HLA-A-A3 and/or B7 affected measles antibody titers more than the presence of MS. These findings suggest that the immune response to measles in these sibships is influenced by the presence of HLA-A-A3 and/or B7 as well as another familial factor. PMID- 6267517 TI - [Our experience with carcinoma of the stomach. Analysis of 618 cases]. PMID- 6267518 TI - [Ultrastructural observations on astrocytoma]. AB - The E.M. findings of 5 brain astrocytomas are described in this paper. Ultrastructural features can point out the glial origin of these tumours, in opposition to Zulch's mesenchymal assumption. PMID- 6267519 TI - Enzyme histochemical changes in some optic projection areas of the goldfish after optic nerve lesions. AB - Enzyme histological changes have been studied in several optic projection areas after right optic nerve lesion in goldfish. An increase in acid phosphatase activity was found in the optic tectum, nucleus rotundus, nucleus geniculatus lateralis and area pretectalis between 2 and 15 days postoperatively. The enzymes glutamate dehydrogenase, lactate dehydrogenase, NADH tetrazolium reductase, cytochrome oxidase, succinate dehydrogenase and beta-hydroxybutyrate dehydrogenase showed a decrease in activity in all or some of these projection areas. No changes were found in acetylcholinesterase activity after optic nerve lesions. Three weeks postoperatively, all enzyme activities returned to the same level as on the normal side. The results are discussed in relation to possible neurotransmitters in goldfish optic terminals. PMID- 6267520 TI - GABA receptors distribution in rat substantia nigra. AB - The perikarya of the dopaminergic and non-dopaminergic neurons contained in the substantia nigra were selectively destroyed by a proper, local injection of 6 hydroxydopamine or kainic acid, respectively. Both lesions resulted in a marked decrease of the nigral GABA-binding sites. The effect of 6-hydroxydopamine was restricted to the high affinity receptors, while kainic acid specifically decreased the low affinity ones. PMID- 6267521 TI - Hypothalamic multiunit activity correlates of the adrenocortical response to stress. AB - The corticotropic response to stress was studied by means of multiple unit activity (MUA) recording from the adrenocorticotropic region of the hypothalamus, and plasma corticosterone (B) determination. MUA was permanently obtained and B was measured at 2, then 5 and 10 min intervals before and after neurogenic (electrical shocks) or systemic (ether inhalation) stress was applied. Experiments were made on steady unanesthetized, unrestrained thalamic pigeons. Post-stress alterations of MUA and B were closely in parallel, exhibiting a rapid and sustained increase in firing rate and shifting by 5-10 min, in corticosteronemia. Three successive and progressively decreasing peaks of MUA and B could be observed. Basal resting values were restored by approximately 90 min. Adrenocorticotropic responses to stress appear to be modulated through neural thalamic and/or rhombencephalic mechanisms. PMID- 6267522 TI - Long-term facilitation of excitatory synaptic transmission in single motor cortical neurones of the cat produced by repetitive pairing of synaptic potentials and action potentials following intracellular stimulation. AB - The effects of postsynaptic firing activity on excitatory postsynaptic potentials (EPSPs) were studied in the motor cortex of anaesthetized cats. Postsynaptic firing was induced by 1-5 nA cathodal current pulses via the recording intracellular microelectrode, while EPSPs were elicited by thalamic, callosal, pyramidal tract and somatosensory stimuli. In 102 cells, EPSP-spike stimulus pairs were applied with 0.2-1/sec frequency and 10-100 msec interstimulus intervals. In 42 neurones, reversible facilitation of paired EPSPs appeared lasting from 4 to 47 min. The synaptic facilitation in most cases was accompanied by membrane depolarization and an increase in input resistance. The effectiveness of current induced action potentials upon test EPSPs provided evidence for the postsynaptic localization of plastic changes occurring in conditioning experiments. PMID- 6267523 TI - Post-amphetamine depression of self-stimulation behavior in rats: prophylactic effects of lithium. AB - Rats reliably interrupted a photobeam for electrical brain stimulation when electrodes were situated in the substantia nigra. The reinforcing value of electrical brain stimulation diminished, markedly, when animals were exposed to long-term amphetamine treatment and then tested in the absence of the drug. Chronic lithium treatment administered in conjunction with amphetamine protected against the development of the post-amphetamine depression of self-stimulation responding. These findings were not related to drug-induced changes in locomotor activity. PMID- 6267524 TI - Regional specificity of benzodiazepine receptor down-regulation during chronic treatment of rats with flurazepam. AB - [3H]Flunitrazepam binding was studied in synaptosomal membranes from rat brain following 4 weeks of chronic treatment with 100-150 mg/kg/day flurazepam. At 12 h after the end of treatment, the brain was removed and dissected into 8 areas: cerebral cortex, hippocampus, cerebellum, corpus striatum, hypothalamus, midbrain thalamus, medulla-pons, and olfactory bulbs. Membranes from each area were extensively 'washed', and saturation binding studies performed. Chronic flurazepam treatment caused a reduction in the apparent number of binding sites (Bmax) that was confined to the cerebral cortex, hippocampus, and medulla-pons, with a possible smaller loss in the olfactory bulbs. The binding constant (KD) was unchanged in all areas studied. PMID- 6267525 TI - Proconvulsant effects in baboons of beta-carboline, a putative endogenous ligand for benzodiazepine receptors. AB - beta-Carboline-3-carboxylic acid ethyl ester (beta-CCE) was tested on two models of epilepsy in the baboon: kainic acid-induced limbic status epilepticus and photosensitive epilepsy. Beta-CCE, at very low doses ranging from 8 to 100 microgram/kg (i.v.), induced a reactivation of the limbic focus and photomyoclonic and generalized seizures in photosensitive and non-photosensitive baboons. The proconvulsant effect of beta-CCE may be associated with its binding to a particular subclass of benzodiazepine receptors. PMID- 6267526 TI - Reciprocal antagonism between ACTH1-24 and beta-endorphin in rats. AB - ACTH1-24 and beta-endorphin simultaneously injected at 5-10 microgram dose into the lateral ventricle, reciprocally suppress most of their respective behavioural effects (stretching-yawning syndrome, sexual excitement and hyperalgesia for ACTH1-24 and catalepsy and analgesia for beta-endorphin). The results obtained support the hypothesis that ACTH1-24 and beta-endorphin might interact antagonistically at CNS level. PMID- 6267527 TI - Drugs and taste aversion. AB - The literature on the effects of drugs on the acquisition and the magnitude of taste aversion is reviewed and discussed. Then, the results of a series of experiments on the effects of phenobarbital and related drugs on taste aversion are reported. A standard taste aversion model was used in all experiments; test drugs were injected prior to drinking in a one bottle situation on the first test day following the taste aversion treatment. Phenobarbital in doses ranging from 20 to 80 mg/kg significantly attenuated taste aversion induced by lithium chloride (LiCl) and x-radiation, the maximal effect occurred with the 60 mg/kg dose. The attenuating effect was found to be dependent upon the magnitude of the aversion to the sapid solution. Phenobarbital completely abolished aversion produced by 0.375 mEq LiCl while the attenuation effect decreased linearly with higher doses of LiCl. Results also indicate that phenobarbital's attenuating effect cannot be solely attributed to its dipsogenic characteristic or to its state dependent learning effect. Attenuation of LiCl aversion to a saccharin solution was also observed following single doses of amobarbital, 30 mg/kg, pentobarbital, 15 mg/kg, and chloropromazine, 0.75 mg/kg. Taste aversion was not affected by other doses of those drugs or by hexobarbital, barbital, and chlordiazepoxide. Phenobarbital's attenuating effect on taste aversion is discussed in relation to other known behavioral and neurophysiological effects of the drug. PMID- 6267528 TI - Small cell cancer of lung; rapid tumor necrosis leading to serious pulmonary infections after intensive chemotherapy. PMID- 6267529 TI - Hepatocellular carcinoma in young adults. PMID- 6267530 TI - Pivmecillinam in uncomplicated urinary tract infections in general practice. PMID- 6267531 TI - Rotavirus detection for the routine laboratory. PMID- 6267532 TI - Drugs & dosages: Claforan (cefotaxime sodium). PMID- 6267533 TI - Immunologic aspects of thyroid disease. AB - Graves' disease and Hashimoto's thyroiditis are autoimmune processes considered distinct diseases in light of current knowledge. In Graves' disease, antibodies directed against the thyrotropin receptor of the thyroid cell stimulate the gland to hyperfunction. The ophthalmopathy of Graves' disease may result from a different autoimmune reaction, directed against orbital tissue. In Hashimoto's thyroiditis, humoral and cellular immune processes are directed against elements of the thyroid cell and result in destruction and glandular hypofunction. PMID- 6267534 TI - Pseudoinflammatory metastatic breast carcinoma of the orbit and lids. AB - A 60-year-old woman presented five years after a radical mastectomy for breast carcinoma, with vague, non-specific complaints referable to the left eye, consisting of ptosis, extraocular motility problems, and irritation, all believed initially to be due to an inflammatory causation. The indurated quality of the involved tissues, coupled with the results of computed tomographic studies, led to the suspicion of the correct diagnosis, namely, metastatic scirrhous carcinoma of the ocular adnexa. Biopsy and electron microscopic studies confirmed this diagnosis. Clinical and pathologic pitfalls in failing to distinguish scirrhous carcinoma from an inflammatory lesion are discussed. PMID- 6267535 TI - The ultrastructure of the adenomatoid odontogenic tumor. AB - An adenomatoid odontogenic tumor (AOT) which occurred in the maxilla of an 8-year old boy was studied by the light and electron microscopy. The tumor was found to contain cells resembling preameloblasts, the stratum intermedium, and the stellate reticulum, suggesting its origin from the enamel organ, in agreement with previous reports. Characteristic ductlike structures are thought to be formed as a result of secretory activity of the tumor cells, rather than degeneration. Duct-lining cells ultrastructurally similar to preameloblasts were found to contain electron-dense granules. These granules are believed to play a role in secretion by tumor cells, a concept not previously considered. The results of previous ultrastructural studies of the AOT are reviewed and summarized. PMID- 6267536 TI - Use of sintered hydroxylapatite in middle ear surgery. PMID- 6267537 TI - [Diagnostic potentials of gamma scintigraphy in spinal injury in children]. PMID- 6267538 TI - Morphological alterations of the adrenal gland following administration of histamine-sensitizing-factor of Bordetella pertussis. PMID- 6267540 TI - [Granular cell myoblastoma in the major bronchi]. PMID- 6267539 TI - [Malignant tumors in newborn infants; oncogenesis, prognosis and therapy]. PMID- 6267541 TI - Serotonergic mediation of descending inhibition from midbrain periaqueductal gray, but not reticular formation, or spinal nociceptive transmission in the cat. AB - Electrical stimulation in the midbrain periaqueductal gray (PAG) and lateral midbrain reticular formation (LRF) strongly suppresses the responses of spinal dorsal horn neurons to noxious heating of the skin. The possible role of serotonin (5-hydroxytryptamine, 5-HT) was investigated by quantitatively comparing certain parameters of descending inhibition from PAG and LRF in normal cats [14,15] and cats whose central 5-HT levels had been reduced by pretreatment with p-chlorophenylalanine (PCPA, 300 or 500 mg/kg i.p., 72 h prior to acute experiment). Single lumbar dorsal horn neuronal responses to noxious radiant heating of glabrous footpad skin(50 degrees C, 10 sec, 1/3 min) were recorded in normal and PCPA-pretreated cats anesthetized with sodium pentobarbital and N2O. Inhibition of neuronal heat-evoked responses during midbrain stimulation (mean frequency 30 Hz, up to 800 microA current intensity) was expressed as percent of the unit's control response in the absence of midbrain stimulation. Inhibition by PAG stimulation of units from cats pretreated with 300 mg/kg PCPA (mean inhibition at 450 microA to 60% of control in 12 units) was not detectably different from that in control (non-pretreated) cats. However, inhibition by PAG stimulation was significantly weaker in units from cats pretreated with 500 mg/kg PCPA (mean to 83.4% of control in 9 units). In the latter group, mean current threshold for inhibition was higher, and slope of current-intensity plots lower, than in the control and 300 mg/kg PCPA pretreatment groups. In contrast, mean inhibition by LRF stimulation was enhanced in the 300 and 500 mg/kg PCPA treatment groups in a dose-related manner. In normal (non-pretreated) cats, systemic administration of the putative 5-HT antagonist methysergide (0.07--1 mg/kg) reduced or abolished inhibition by PAG stimulation in each of 8 units. Low doses of methysergide had little or no effect on inhibition produced by LRF stimulation in 6 units. The results suggest pharmacologically distinct mechanisms of inhibition produced by stimulation in PAG and LRF. PMID- 6267542 TI - Effect of transcutaneous electrotherapy on CSF beta-endorphin content in patients without pain problems. AB - To test the hypothesis of opiate-like peptide release after transcutaneous electrotherapy we measured beta-endorphin cerebrospinal fluid (CSF) content in 13 patients without pain problems. The results indicate a time dependent increase of CSF beta-endorphin in the group of patients studied. This fact suggests that the analgesic properties of the treatment may be ascribed to an involvement of the endogenous opiates system, independently from the basal clinical conditions of the patients. PMID- 6267543 TI - Separation of Isospora (Toxoplasma) gondii cysts and cystozoites from mouse brain tissue by continuous density-gradient centrifugation. AB - A simple, quick and reproducible method consisting of density-gradient centrifugation of homogenized infected mouse brain tissue on Percoll is described for the isolation and purification of cysts of Isospora (Toxoplasma) gondii. A 100% recovery of cysts, with 74.2% in a single fraction with a specific gravity of 1.056, was obtained by overlaying homogenates of infected mouse brains on a pre-formed Percoll gradient and centrifugation at low g forces. With this procedure recovery was independent of the age of the cysts. Titration of purified cystozoites showed there to be no loss of infectivity. PMID- 6267544 TI - Evasion of the oxidative microbicidal activity of human monocytes by trypomastigotes of Trypanosoma dionisii. AB - Trypomastigotes of Trypanosoma dionisii, a stercorarian trypanosome from bats, are effectively killed by neutrophils from human peripheral blood but are less sensitive to the cytotoxic action of human monocytes. The mechanism of killing appears to involve peroxidase and hydrogen peroxide. Trypomastigotes are as effective as epimastigotes in inducing the formation of hydrogen peroxide by effector cells. They are, however, less sensitive than epimastigotes to the cytotoxic effect of peroxidase and hydrogen peroxide. They are therefore susceptible to the high concentrations of peroxidase found in the phagosome of the neutrophil, but resist the lower levels encountered in monocytes. PMID- 6267545 TI - Isolation and partial characterization of the tegumental outer membrane of adult Schistosoma mansoni. AB - Incubation of adult Schistosoma mansoni at 37 degrees C in chemically defined media caused the shedding of variable amounts of the parasite's tegument. In phosphate-buffered saline, pH 7.4, 37% of 125I-labelled wheat germ agglutinin which was attached to the schistosome surface was released within 5 min. When the released material was collected by centrifugation at 55 000 g for 1 h, the pellet was seen to consist of components of the parasite tegument and contained 1% of the parasite protein and 6.2% of the 5'-AMPase activity. By monitoring the release of the gut enzyme, haemoglobinase, it was shown that predominantly tegumental material was released under these conditions. The material released from the parasite was separated by discontinuous sucrose gradient centrifugation into 4 major fractions and it was shown that a material banding at low density was highly enriched in vesicles of parasite outer membrane. Major polypeptides of apparent molecular weights 135 000, 110 000, 90 000, 65 000, 47 000 and 40 000 and glycoproteins of apparent molecular weights 135 000, 120 000, 65 000, 63 000 and 30-40 000 were identified in this fraction. Comparison of the distribution of 5'-AMPase activity and the contents of each fraction as revealed by ultrastructural examination showed that this enzyme is a good marker for the tegumental outer membrane. PMID- 6267546 TI - Angiotensin II metabolism by tissues from developing rats. AB - Asp1-125I-Tyr4-angiotensin II (125I-AII) was degraded during incubation with rat plasma or homogenates of liver or kidney. The electrophoretic profile of peptide fragments revealed that the disappearance of 125I-AII was first order and was accompanied by an accumulation of 125I-tyrosine in the incubation medium. The only other metabolites of angiotensin AII detectable by peptide mapping were the amino-terminus tetrapeptide and the carboxy-terminus hexapeptide. The appearance of these fragments was highly variable, suggesting that endopeptidases did not constitute the ultimate cleavage of angiotensin II hydrolysis. The half-life of 125-AII in plasma or liver homogenates did not change with age (approximately 8 to 12 and 6 to 9 min, respectively). In contrast, the rate of disappearance of 125I-AII in homogenates of rat kidney depended upon the age of the rat from which the tissue was obtained. The half-life of 125AII decreased three-fold (from approximately 8.3 to 2.8 min) between 2 wk after birth and adult (approximately 8 wk). This increase in the rate of metabolism of 125I-AII was accompanied by a concomitant two-fold, age-related increase in the rate of appearance of 125I tyrosine in the reaction mixture containing renal tissue. PMID- 6267547 TI - Biological actions mediated by membrane receptors. PMID- 6267548 TI - Adrenocortical tumor in a patient with congenital adrenal hyperplasia due to 21 hydroxylase deficiency. AB - An adrenal cortical tissue tumor developed in a patient with poorly controlled salt-losing congenital adrenal hyperplasia. A 16-year-old girl became progressively virilized from 13 to 16 years of age. Base line serum progesterone, 17-hydroxyprogesterone, and testosterone levels were high and there was a diurnal pattern of the hormones. Initially elevated urinary 17-ketosteroid and serum steroid levels were decreased by high dose dexamethasone therapy, and at laparotomy an adenoma was found in the cortex of the hyperplastic left adrenal gland. It is inferred that persistent adrenocorticotrophic hormone stimulation may result in neoplastic transformation of hyperplastic adrenal cortical tissue in patients with congenital adrenal hyperplasia. PMID- 6267549 TI - The search for the specific factor in scurvy. PMID- 6267550 TI - Organochlorine insecticides and general anesthetics: a comparison of their neural effects. PMID- 6267551 TI - [CT of hepatocellular carcinoma: analysis of contrast-enhanced CT using CT arteriography (author's transl)]. PMID- 6267552 TI - [Relationship between dietary fibers and constipation (author's transl)]. AB - Twenty-two women suffering from constipation were compared with an equal number of controls. Although both groups had similar mean daily total dietary fiber intake (12.4 and 12.7 g respectively) and mean daily cereal fiber intake (3.3 and 3.6 g respectively), the mean mouth-to-anus transit time for food was significantly longer (p less than 0.01) in constipated women (66.8 h) than in controls (48.5 h). PMID- 6267554 TI - [Cyclic AMP content in peripheral blood T and B lymphocytes in healthy subjects and patients with chronic lymphatic leukemia]. PMID- 6267553 TI - [Necrotizing enterocolitis and cytomegalovirus infection (author's transl)]. AB - During an 18-month period, 11 cases of necrotizing enterocolitis (NEC) were diagnosed in infants treated in Neonate Department. This represents 1% of total admissions. Six cases occurred during hospitalization. Clinically, the disease took three different forms: surgical form, medical form responding well to exclusive parenteral feeding and isolated haemorrhagic form, which deserves discussion. Seven of these infants had cytomegalovirus (CMV) infection. NEC accounted for 22% of clinical symptoms in CMV infection. These data suggest that the cytomegalovirus may act as aggravating factor in NEC. PMID- 6267555 TI - [The circadian rhythm of the absorptive function of the small intestine in man in pharmacokinetic and histochemical studies]. PMID- 6267556 TI - Neurotropic action of MSH/ACTH 4-10 on neuromuscular function in hypophysectomized rats. AB - These studies were designed to determine whether the previously demonstrated [24] enhancement of neuromuscular function by MSH/ACTH 4-10 is due to peptide action on the neurogenic and/or myogenic elements involved. The nerve muscle unit studied incorporated the sciatic nerve and its branches, and the extensors digitorum longus and brevis in the hypophysectomized rat, in situ. Parameters investigated included muscle action potentials (MAP) and muscle contractions (MC) during 30 min of stimulation (supramaximal, 10/sec; 0.05 msec duration). Resting membrane potentials and miniature endplate potential (mepp) characteristics were investigated in situ at neuromuscular junctions in the extensor digitorum brevis. Hypophysectomy results in markedly deleterious changes in neuromuscular function which can be partially alleviated by the administration of ACTH 4-10 (0.01 microgram/kg). This dosage increases MAP and MC amplitudes and reduces fatigue. Higher dosages (1.0 microgram/kg) have a depressing effect on these parameters. The facilitatory actions of ACTH 4-10 are abolished when the muscle is stimulated directly or stimulated through the peripheral stump of the cut nerve. ACTH 4-10 increases mepp frequency (a presynaptic event) but does not affect postsynaptic characteristics as measured by the resting membrane potential. These results indicate that MSH/ACTH 4-10 influences skeletal muscle function through a neurotropic action mediated by spinal motoneurons. Changes in the central excitatory state of higher motor centers are possibly involved. PMID- 6267557 TI - Effects of alpha-MSH and beta-endorphin on startle reflex in rat. AB - Twelve rats received peripheral injections (20 micrograms/rat) of alpha-MSH, beta endorphin or the vehicle solution and were subsequently tested for the motor and cardiac responses to repeated presentations of intense acoustic stimuli. Each subject received all treatments in a counterbalanced order with 3-day periods between each session. beta-Endorphin tended to decrease the amplitude of the habituated motor startle reflex, while alpha-MSH produced a slight increase in basal heart rate during the habituation session. Neither peptide had any effect on the cardiac response to intense acoustic stimulation. The effects of the two peptides were not directly antagonistic but they are consistent with the hypothesis that complex attentional processes were facilitated by MSH/ACTH fragments and inhibited by the endorphins. PMID- 6267558 TI - Cholecystokinin receptors in brain: effects of obesity, drug treatment, and lesions. AB - High affinity binding sites specific for cholecystokinin (CCK) and related peptides have been identified in brain. These receptors are regionally distributed, with the greatest density in the caudate nucleus and olfactory bulbs. The number of forebrain CCK receptors increases postnatally to a peak density at 12 days of age and then falls to adult concentrations by 26 days of age. Cerebral cortical (but not hypothalamic) CCK receptors were 15-18% higher (p less than 0.05) in obese rats and mice when compared with their lean littermates; however, CCK receptors were unchanged after 96 hours of fasting in normal rats. Chronic reserpine treatment (0.75 mg/kg/day X 7 days) caused a 48% increase (p less than 0.001) in the number of cerebral cortical CCK receptors, but had no effect on receptors in the caudate nucleus. Chronic d-amphetamine sulfate (5 mg/kg twice daily X 7 days) had no effect on CCK binding in cortex or caudate nucleus. Approximately 75% of the CCK receptors in the caudate nucleus are susceptible to destruction by kainic acid, indicating that they are predominantly localized to neuronal cell bodies; the remaining 25% were destroyed by severing caudal afferents to the caudate nucleus, indicating a possible presynaptic localization. PMID- 6267559 TI - Inhibition of opiate receptor binding by zinc ions: possible physiological importance in the hippocampus. AB - In the rat and guinea pig hippocampus, the staining pattern for enkephalin (by immunocytochemistry) and for zinc (by the Timm method) is congruent and confined to the mossy fiber system. The stereospecific binding of 3H-enkephalinamide (2-D Ala-5-L-methionine) to opiate receptors can be totally blocked by zinc ions, both in the hippocampus and in the cerebral cortex, the basal ganglia and the rest of the forebrain. Scatchard analysis of binding isotherms indicates that this inhibitory effect involves a decrease in receptor affinity, whereas the number of binding sites is unaffected. Thiol reductants can reactivate Zn2+-inhibited opiate receptors with a potency correlating to their redox potential (Eo). Thus, our data suggest that zinc ions represent modulators of opiate receptor binding in the hippocampus and that they work through a redox reaction with essential SH groups of opiate receptors. PMID- 6267560 TI - Localization and opiate receptor binding of enkephalin, CCK and ACTH/beta endorphin in the rat central nervous system. AB - We have examined the distributions of ACTH, CCK and enkephalin immunoreactive nerves in the rat central nervous system and compared the pattern obtained with that of opiate receptors. In addition, a radioreceptor assay has been employed for studying the possible functional interactions between these peptides and opiate receptors. Our results suggest that: (a) The distribution of enkephalin, CCK and ACTH/beta-endorphin immunoreactive nerve terminals is sufficiently similar to suggest functional interaction between these neuropeptides. (b) The CCK immunoreactive nerves display a distribution similar to that of enkephalin, but the main endogenous CCK forms do not bind to opiate receptors. However, opioid peptides and CCK may interact in many brain regions via binding to different, but functionally interacting receptors. (c) The ACTH immunoreactive nerves, which seem also to contain beta-endorphin, shows a partially overlapping distribution with the enkephalinergic systems. Further, ACTH and its fragments bind to opiate receptors. This suggests that ACTH could be an endogenous opioid ligand. PMID- 6267561 TI - Muscarinic cholinergic influences on ACTH and beta-endorphin release mechanisms in human subjects. PMID- 6267562 TI - Modification of the actions of ethanol by centrally active peptides. AB - Ethanol (2.0-5.0 g/kg, IP) caused a dose-related impairment of the aerial righting reflex of mice 60 min after injection. Ethanol (3.5 g/kg, IP) given simultaneously with neurotensin (30 micrograms, IC), bombesin (30 micrograms, IC) or beta-endorphin (20 micrograms, IC) caused a greater impairment of the reflex than ethanol alone. Simultaneous treatment with ethanol (4.0 g/kg, IP) and thyrotropin-releasing hormone (TRH, 3.0-30 micrograms, IC) caused less impairment of this measure than ethanol alone. None of the peptides altered the height of aerial righting when administered alone, or when administered with ethanol no peptide altered blood or brain ethanol content. Unexpectedly, TRH (20 and 40 mg/kg, IP) potentiated the action of ethanol by increasing punished licking in water-deprived rats, rather than antagonizing this acute action of ethanol. Like ethanol (1.0 and 2.0 g/kg, IP), beta-endorphin (100 micrograms, IC) suppressed ethanol-withdrawal tremor and audiogenic-seizure susceptibility in ethanol dependent rats. beta-Endorphin (1 microgram) and bombesin (10 and 30 micrograms, IC) reduced only audiogenic-seizure susceptibility. TRH (10-100 micrograms, IC, or 1-40 mg/kg, IV) and neurotensin (10-100 micrograms, IC) had no effect on these ethanol-withdrawal signs. These findings suggest that centrally active peptides may play a role in certain acute and chronic actions of ethanol. Because TRH, neurotensin, bombesin and beta-endorphin do not alter all actions of ethanol in the same way, an interaction of ethanol with many functionally independent neuronal circuits is suggested. PMID- 6267563 TI - [Effect of acute pancreatitis on enzymatic reactions of the pyloric glands]. PMID- 6267564 TI - [Effect of thyroid hormones on cell metabolism]. PMID- 6267565 TI - The lack of affinity of prostaglandins to dopaminergic and opiate receptors in the rat striatum. AB - The aim of this paper was to study whether prostaglandins (PGs) E1, E2 and F2 alpha affect the binding of specific ligands for dopaminergic or opiate receptors 3H-spiroperidol or 3H-naloxone in the rat striatum. The PGs, even in very high concentrations, did not change 3H-spiroperidol or 3H-naloxone binding to rat striatal membranes in vitro. This indicates that in the striatum of rats PGs do not interact directly with dopaminergic and opiate receptors. PMID- 6267566 TI - Effect of adenosine on electrical activity in guinea-pig atrium. AB - Adenosine abolished action potentials and slowed down depolarization in the sinus node cells, and depressed the slow component in the working fibers. Noradrenaline and dibutryl cAMP did not counteract the effects of adenosine in the working myocardium whereas in the pacemaker, dibutryl cAMP alone evoked low frequency spontaneous activity. PMID- 6267567 TI - [Protein phosphorylation as a mechanism of metabolic regulation]. PMID- 6267568 TI - Cytomegalovirus infection with carditis, hepatitis, and anemia. PMID- 6267570 TI - Penile lesions: a generalist's guide. AB - Penile lesions are a discomfiting affliction demanding skillful diagnosis and management by the primary care physician. This article discusses and illustrates 14 common types, delineating characteristics, course, and treatment. PMID- 6267569 TI - Recent advances in nuclear cardiology. 1. "Hot-spot" and "cold-spot" myocardial scintigraphy. AB - Nuclear cardiology is a comparatively new field of cardiovascular medicine in which technologic advances have provided relatively noninvasive means of evaluating cardiovascular abnormalities. The purpose of this two-part review is to emphasize some important recent advances and to place in perspective the advantages and disadvantages of those new techniques that are particularly useful clinically. PMID- 6267571 TI - Sarcoidosis and chronic sensory neuropathy. AB - A patient with long-standing sensory peripheral neuropathy is described who finally presented with acute pulmonary sarcoidosis after a period of 18 years. Purely sensory neuropathy presumably due to sarcoidosis of this duration has not been reported before. PMID- 6267572 TI - Adult bronchiolitis and parainfluenza type 2. PMID- 6267573 TI - Mucus-secreting 'signet-ring' cells in CSF revealing the site of primary cancer. AB - A case is reported of leptomeningeal carcinomatosis in which identification of mucus-secreting 'signet-ring' carcinoma cells in the CSF allowed diagnosis of an otherwise asymptomatic gastric cancer. When lumbar puncture is performed, careful cytological examination of the CSF should be carried out in any undiagnosed patient with neurological symptoms and signs. PMID- 6267574 TI - Herpes encephalitis and herpetic corneal disease. AB - A case of herpes encephalitis is reported in a patient who had cranial irradiation and high dose steroids for a cerebral neoplasm. Before radiotherapy the patient had had herpetic infections of the skin and eye. PMID- 6267575 TI - Comparison of inactivated and live infectious bursal disease virus vaccines in White Leghorn breeder flock. AB - Leghorn breeder chickens, which had received live infectious bursal disease (IBDV) virus vaccine at 12 weeks of age and had been injected subcutaneously at 20 weeks of age with an inactivated IBDV oil emulsion vaccine, produced very high antibody titers which persisted for at least 9 months and were more uniform than those obtained from breeders receiving only the live IBDV vaccine. Breeders vaccinated with the inactivated IBDV oil emulsion vaccine at 12 and 20 weeks of age had antibody titers higher than breeders which received only the live IBDV vaccine at 12 weeks of age; titers were lower than in the group which received both the live and inactivated oil emulsion IBDV vaccines. Maternal antibody levels in chickens derived from parent flocks vaccinated with the inactivated oil emulsion IBDV vaccine were higher and more uniform than in chickens derived from parent flocks vaccinated with the live IBDV vaccine. Maternal antibody persisted longer in chickens derived from parent flocks vaccinated at 20 weeks of age with the inactivated oil emulsion IBDV vaccine than in chickens vaccinated by the other procedures. The titers remained quite high up to 16 days of age. PMID- 6267576 TI - Hemagglutinin responses in Japanese quail treated with exogenous adrenocorticotrophin. AB - Injections of exogenous ACTH in chickens are known to cause immunosuppression provided that ACTH administration is properly timed with respect to immunization. In random-bred Japanese quail, injections of ACTH at various times both before and after immunization with erythrocyte antigens did not significantly alter antibody responses. This finding was consistent whether the ACTH was administered over a 4 hr or a 6 day period, and whether sheep or chukar erythrocytes were used as the antigen. PMID- 6267577 TI - Immune response and disease resistance in chickens. I. Selection for high and low titer to Salmonella pullorum antigen. AB - A selection experiment for high and low anti-Salmonella pullorum antibody titer was carried out over four generations within the B1B1 blood group genotype in chickens. The study was aimed primarily at identifying different response patterns controlled by immune response genes linked to the B system, the major histocompatibility complex of the chicken. Maximal divergence was obtained in the third generation of selection when agglutination titers of 1/320 and 1/80 in B1B1 high and low responders, respectively, were reached. Immune response of S. pullorum was deduced to be controlled by polygenes. The B1B1 population, selected for high immune response to S. pullorum antigen, consistently had greater total mortality as well as greater susceptibility to challenge with Marek's disease virus compared with B1B1 population selected for low response. This, however, is believed to be a consequence of random drift of genes for disease resistance in the relatively small populations and not a direct consequence of selection for high or low S. pullorum titer. PMID- 6267578 TI - B-haplotype influence on Marek's disease, Rous sarcoma, and lymphoid leukosis virus-induced tumors in chickens. AB - Experiments were conducted to establish whether B-haplotype genes that determine resistance to RSV-induced tumors would also influence resistance to Marek's disease and lymphoid leukosis. Matings of line 6(3) x 15(1) F3 or F4 breeders segregating for the Ea-B locus antigens that are markers for B2 and B5 haplotypes of the B major histocompatibility complex were made to produce B2B2, B2B5, and B5B5 chicks. The chicks were infected with a standard inoculum of one of the three tumor viruses in separate experiments. The B2 haplotype from 6(3) conveyed greater resistance to tumors induced by all three viruses than the B5 from 15(1) chickens. This finding suggests that some gene(s) in the B-haplotype may determine a general ability to resist tumor formation or cause tumor regression. PMID- 6267579 TI - Effect of subcutaneous pox vaccination of young chicks on immune responses and weight gains. AB - Two fowl pox and two pigeon pox vaccines were administered subcutaneously in the dorsum of the neck of specific-pathogen-free (SPAFAS) chicks at day of hatch in separate studies. Treatment levels used were 1:2, 1:10, or 1:50 dilution of the recommended wing web dose. Both pigeon pox vaccines and one fowl pox vaccine depressed body weight gains significantly by day 14. Mean body weight gains of female chicks were less affected by pigeon pox vaccines than by fowl pox vaccines. The mean hemagglutination-inhibition (HI) antibody titer to Newcastle disease virus (NDV) of chicks given one pigeon pox vaccine at the 1:2 dilution was significantly lower (P less than .01) than titers of sham-treated controls. The number of immunoglobulin-M (IgM) secreting cells in the spleen was significantly less (P less than .05) at day 14 in all pox vaccinated chicks when compared to sham-treated controls. PMID- 6267580 TI - Serological responses to Mycoplasma synoviae in chickens infected with virulent or avirulent strains of Marek's disease virus. AB - The pathogenicity and immunosuppressive capability of five strains of Marek's disease herpesvirus (MDHV) was examined. Three of the strains (ALA, MISS, NCS) were isolated from flocks experiencing vaccine breaks while the other two strains (GA, HN) represented prototype virulent and avirulent viruses. Pathogenicity of MDHV strains was evaluated on their ability to cause mortality, their ability to cause gross or microscopic lesions, and the median latent period to death (MLPD) for each strain. Antibody responses to Mycoplasma synoviae (MS) were tested by the serum plate agglutination and hemagglutination inhibition tests. Chicks infected with the virulent strains of MDHV had greater mortality, greater lesion incidence, and shorter MLPD that did chicks infected with the avirulent HN strain. Infection with virulent strains reduced the antibody response to MS and caused severe bursal lesions. Chicks infected with the avirulent HN strain exhibited a slight immunosuppression, but they had no evidence of bursal destruction. PMID- 6267581 TI - Acetylcholine-induced cation translocation across cell membranes and inactivation of the acetylcholine receptor: chemical kinetic measurements in the millisecond time region. AB - Acetylcholine-induced flux of inorganic ions across membranes and inactivation of the acetylcholine receptor were measured at pH 7.0, 1 degrees C, over a 5000-fold concentration range of acetylcholine. Receptor-containing electroplax membrane vesicles prepared from Electrophorus electricus and a quench-flow technique were used, allowing flux to be measured in the 2-msec to 1-min time region. Five different measurements were made: (i) rate of ion translocation with the active state of the receptor, (ii) rate of the slower ion translocation after equilibration of active and inactive receptor states, (iii) rate of inactivation, (iv) equilibrium between active and inactive forms of the receptor, and (v) reactivation of inactivated receptor. The kinetics of the steps in the receptor controlled ion flux follow single-exponential rate laws, and simple analytical expressions for their ligand concentration dependence can be used. Thus, the rate and equilibrium constants in a scheme that relates the ligand binding steps to ion translocation could be evaluated. It was found that the dependence of the receptor-controlled ion translocation over the concentration range investigated obeys the integrated rate equation based on the proposed mechanism. The flux rate before inactivation was approximately 10(7) ions sec-1 per receptor, which is comparable with that measured electrophysiologically in muscle cells. The half time of inactivation is approximately 100 msec when the receptor is saturated with acetylcholine. The specific reaction rate of the ion translocation (J) is 3 X 10(7) M-1 sec-1. The results support a minimum reaction mechanism previously proposed on the basis of experiments in which carbamylcholine was used. PMID- 6267582 TI - Complete nucleotide sequence of minicircle kinetoplast DNA from Trypanosoma equiperdum. AB - The kinetoplast DNA of Trypanosoma equiperdum is composed of about 3000 supercoiled minicircles of 1000 base pairs and about 50 supercoiled maxicircles of 23,000 base pairs topologically interlocked so as to form a compact network. Minicircles of T. equiperdum, which are homogeneous in base sequence, were purified by equilibrium CsCl centrifugation and used as starting material for DNA sequence analysis. One minicircle is composed of 1012 base pairs and has an adenine.thymine base pair content of 72.8%. The termination codons are uniformly distributed along the molecule and restrict the coding potentiality of the molecule to oligopeptides of about 20 amino acids. The molecule contains three dyad symmetries and a sequence of 12 nucleotides is repeated six times. We also noted the presence of a region of about 130 base pairs that is almost perfectly homologous with that of the minicircles from the closely related species T. brucei. PMID- 6267583 TI - Analysis of two divergent rat genomic clones homologous to the transforming gene of Harvey murine sarcoma virus. AB - Harvey murine sarcoma virus (Ha-MuSV) is a mouse-rat recombinant retrovirus that encodes a protein designated p21, required for virally induced transformation. Using a radiolabeled DNA fragment from the p21 coding region, we have detected homologous DNA sequences in the normal DNA of rats and of several other vertebrate species. Moreover, many tested cells from these species contain low levels of a p21 protein that is highly related to viral 21. Now we report two independent fragments from normal rat DNA containing sequences (sarc) homologous to the Ha-MuSV transforming region that were cloned in the bacteriophage vector Charon 4A. Sarc sequences in the one fragment are completely colinear with the viral sequences and share apparently all restriction endonuclease sites. Sarc sequences in the second fragment have several sets of intervening sequences and lack some restriction endonuclease sites found in the viral transforming region. Despite the presence of these intervening sequences in the second sarc fragment, we have been able to ligate this sarc fragment to the long terminal repeat sequence of HaMuSV and to induce cellular transformation and high levels of p21 expression upon transfection of this DNA to NIH 3T3 mouse cells. These results suggest that elevated levels of p21, normally expressed at low levels in a variety of cells, can induce cellular transformation. PMID- 6267584 TI - Hydrogen bonding, overlap geometry, and sequence specificity in anthracycline antitumor antibiotic.DNA complexes in solution. AB - We have deduced structural aspects of the intercalation complex of the anthracycline antitumor antibiotic daunomycin and its analogs with the synthetic DNA poly(dA-dT) by 1H and 31P NMR in high-salt solution. We demonstrate that the base pairs are intact at the antibiotic binding site and that the anthracycline phenolic hydroxyls form intramolecular hydrogen bonds with the quinone carbonyls and are shielded from solvent in the intercalation complex. The complexation shifts of the exchangeable phenolic and nonexchangeable aromatic protons demonstrate that rings B and C of the anthracycline chromophore overlap with adjacent base pairs, while anthracycline ring D passes right through the intercalation site in the complex. We observe two resolved 31P resonances attributable to the dA-dT and dT-dA phosphodiester linkages in the phosphorus spectra of the neighbor-exclusion daunomycin.poly(dA-dT) complex. This suggests that the anthracycline antitumor antibiotic exhibits a sequence specificity in its intercalation complex with alternating purine-pyrimidine synthetic DNAs in solution. These conclusions on hydrogen bonding and overlap geometry at the intercalation site and sequence specificity for the daunomycin.poly(dA-dT) complex in solution are in agreement with the structure of the daunomycin.dC-dG dT-dA-dC-dG hexanucleotide duplex crystalline complex at atomic resolution published recently [Quigley, G. J., Wang, A. H.-J., Ughetto, G., van der Marel, G., van Boom, J. H. & Rich, A. (1980) Proc. Natl. Acad. Sci. USA 77, 7204-7208]. PMID- 6267585 TI - Identification and quantification of the rat hepatocyte asialoglycoprotein receptor. AB - The asialoglycoprotein receptor from rat liver was purified by solubilization and affinity chromatography on asialoorosomucoid-Sepharose. The preparation yielded four distinct polypeptides of Mr 40,000-120,000. We prepared a monoclonal antibody that both immunoprecipitates solubilized receptor activity and blocks the binding of galactose-terminal glycoproteins to immobilized receptor. The monoclonal antibody and a rabbit antireceptor antiserum immunoprecipitated all four polypeptide species. Peptide analysis by two-dimensional chromatography of the individual 125I-labeled species showed nearly identical patterns, which also suggested that the four polypeptides have a similar primary structure. To identify and quantitate the asialoglycoprotein receptor on the hepatocyte cell surface, intact cells were iodinated with lactoperoxidase, and the solubilized membranes were treated with antireceptor antibody. The Mr 55,000 and Mr 65,000 species were the major species found. Our results suggest that the Mr of the surface receptor is at least 55,000 and that it comprises between 1-2% of the iodinated hepatocyte surface protein. PMID- 6267586 TI - Translational control in lysates of Drosophila melanogaster cells. AB - Cell-free protein-synthesizing systems made from Drosophila melanogaster cells were used to study the translational control induced in these cells by heat shock. Lysates of normally growing cells, termed 25 degrees C cells, translate both normal and heat shock mRNAs. Lysates of cells heat shocked at 36 degrees C for 1 hr, termed 36 degrees C cells, translate preferentially heat-shock mRNAs and a few 25 degrees C cell mRNAs. Thus, both lysates appear to reproduce the control displayed in vivo. Both lysates are optimally active at 28 degrees C, and all translations are done at that temperature, demonstrating that, once established, the discrimination system does not require heat-shock temperature for its activity. Addition of crude ribosome fractions from 25 degrees C cell lysates to lysates from heat-shocked cells "rescues" translation of 25 degrees C cell mRNA, which suggests that the discriminating elements are associated with ribosomes. Neither the heat-shock crude ribosome supplements nor the soluble fractions have any effect on either lysate. The experiments also show that RNA selection is determined by some feature of the RNA structure that is insensitive to protease digestion and phenol/chloroform extraction. The essential structural feature may not be unique to Drosophila mRNAs because the Drosophila lysate is capable of discriminating among mRNAs from other organisms. PMID- 6267587 TI - Forskolin: unique diterpene activator of adenylate cyclase in membranes and in intact cells. AB - The diterpene, forskolin [half-maximal effective concentration (EC50), 5-10 microM] activates adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] in rat cerebral cortical membranes in a rapid and reversible manner. Activation is not dependent on exogenous guanyl nucleotides and is not inhibited by guanosine 5'-O-(2-thiodiphosphate) when assayed with adenosine 5'-[beta, gamma imido]triphosphate as substrate. GTP and GDP potentiate responses to forskolin. The activations of adenylate cyclase by forskolin and guanosine 5'-[beta, gamma imido]triphosphate p[NH]ppG are not additive, whereas activations by forskolin and fluoride are additive or partially additive. The responses of adenylate cyclase to forskolin or fluoride are not inhibited by manganese ions, whereas the response to p[NH]ppG is completely blocked. Activation of adenylate cyclase by forskolin is considerably greater than the activation by fluoride in membranes from rat cerebellum, striatum, heart, and liver, while being about equal or less than the activation by fluoride in other tissues. Forskolin (EC50, 25 microM) causes a rapid and readily reversible 35-fold elevation of cyclic AMP in rat cerebral cortical slices that is not blocked by a variety of neurotransmitter antagonists. Low concentrations of forskolin (1 microM) augment the response of cyclic AMP-generating systems in brain slices to norepinephrine, isoproterenol, histamine, adenosine, prostaglandin E2, and vasoactive intestinal peptide. Forskolin would appear to activate adenylate cyclase through a unique mechanism involving both direct activation of the enzyme and facilitation or potentiation of the modulation of enzyme activity by receptors or the guanyl nucleotide binding subunit, or both. PMID- 6267588 TI - Molecular cloning and comparative analyses of the genomes of simian sarcoma virus and its associated helper virus. AB - Closed circular viral DNA of simian sarcoma virus (SSV) and simian sarcoma associated virus (SSAV) obtained from acutely infected dog cells was purified on preparative agarose gels, cleaved with EcoRI, and cloned in the phage lambda vector Charon 21A. The cloned 9-kilobase SSAV genome (B11) has the same restriction map as the bulk of the unintegrated linear SSAV DNA intermediate. Heteroduplex analysis between an SSV clone (lambda-C60) and an SSAV clone (lambda B11) showed two substitution loops and one deletion loop. By using detailed restriction enzyme mapping and electron microscopic analysis, we showed that one of the substitution loops corresponds to an inversion of one of the two long terminal repeat units and adjacent cellular sequences in C60. The other substitution loop mapped close to the 3' long terminal repeat. At least part of this region was shown to contain SSV-specific sequences not shared by SSAV. The 1.9-kilobase deletion mapped at 3.5-5.5 kilobases of the linear SSAV genome, corresponding to most, if not all, of the pol gene. PMID- 6267589 TI - On the mechanism of retrovirus-induced avian lymphoid leukosis: deletion and integration of the proviruses. AB - There is considerable evidence that infection by avian lymphoid leukosis viruses can led to tumor development in the target organ of the host. The mechanism by which virus-induced oncogenic transformation occurs, however, is not clearly understood. As a first step toward deciphering this process, we have characterized the proviruses of the lymphoid leukosis viruses in DNAs extracted from the leukotic and metastatic tumors by using restriction enzyme digestion and filter hybridization analysis with radioactive probes specific for the infecting genome. Our results indicate (i) that lymphoid leukosis tumors are clonal in origin; (ii) that there are multiple sites in the cellular genome of the target tissue where the virus DNA can integrate and that, in the majority of the tumors, at least one such site of each tumor is adjacent to a cellular sequence related to the oncogene of MC-29 virus; and (iii) that deletions and other structural alterations in the proviral DNA may facilitate tumorigenesis. PMID- 6267591 TI - Isolation of a molybdenum--iron cluster from nitrogenase. AB - A molybdenum-iron cluster (Mo-Fe cluster) containing 6 Fe atoms per Mo was isolated by methyl ethyl ketone extraction of component I of nitrogenase from Azotobacter vinelandii. The cluster has no EPR signal in the g = 4 region but has an intense signal at g = 2.05 and 2.01. After the cluster was transferred from methyl ethyl ketone to N-methylformamide, the signal in the g = 2 region disappeared and a signal similar to that found with Fe-Mo cofactor appeared. The Mo-Fe cluster is the EPR-active center that undergoes reversible oxidation reduction during catalytic turnover at the active site of the enzyme. In contrast to the Fe-Mo cofactor, which contains 8 Fe atoms per Mo, the Mo-Fe cluster failed to activate either inactive component I in extracts of A. vinelandii mutant strain UW45 or tungsten-containing component I from wild-type A. vinelandii. On the other hand, the Mo-Fe cluster showed as much acetylene-reduction activity with sodium borohydride as the reductant as did the Fe-Mo cofactor. Like nitrogenase-dependent and Fe-Mo cofactor-dependent acetylene reduction, the Mo-Fe cluster-dependent acetylene reduction is strongly inhibited by carbon monoxide. PMID- 6267590 TI - Resolution of cointegrates between transposons gamma delta and Tn3 defines the recombination site. AB - Transposition of the genetically related insertion elements gamma delta and Tn3 is thought to involve two steps. In the case of transposition from one replicon to another, the first step is fusion of the parent and target replicons with the element appearing in direct orientation at the two junctions. In a subsequent reaction, the cointegrate structure is resolved via a site-specific recombination event. I have constructed two plasmids, each carrying segments of gamma delta and Tn3, that contain the internal resolution site. The tnpR gene product encoded by either Tn3 or gamma delta mediates intramolecular recombination between these two sites. The product of this recombination is a hybrid region that contains gamma delta and Tn3 sequences fused at the point of crossover. DNA sequence analysis of such recombinants indicates that the recombination occurs within a 19-base-pair (bp) region of exact homology between gamma delta and Tn3. The site lies in the 160-bp center intercistronic region, 50 bp before the beginning of the tnpA gene. My results therefore suggest a model for the coupled regulation of the repressor (tnpR) and the transposase (tnpA) genes and site-specific recombination of transposition intermediates. The Tn3/gamma delta recombination system and bacteriophage lambda integration are compared. PMID- 6267592 TI - ATP-driven active transport in right-side-out bacterial membrane vesicles. AB - Membrane vesicles from Salmonella typhimurium induced for phosphoglycerate transport, were loaded with pyruvate kinase and ADP by lysing spheroplasts under appropriate conditions. Vesicles so prepared catalyze active transport of proline and serine in the presence of phosphoenolpyruvate; this activity is abolished by the protonophore carbonyl cyanide-m-chlorophenylhydrazone and by the H+-ATPase inhibitor N,N' dicyclohexylcarbodiimide but not by anoxia or cyanide. In contrast, D-lactate-driven active transport is abolished by the hydrazone and by anoxia or cyanide but not by the carbodiimide. Moreover, phosphoenolpyruvate does not drive transport effectively in vesicles that lack the phosphoglycerate transport system. The results are consistent with an overall mechanism in which phosphoenolpyruvate gains access to the interior of the vesicles by means of the phosphoglycerate transporter and is then acted on by pyruvate kinase to phosphorylate ADP. ATP formed inside of the vesicles is then hydrolyzed by the H+ ATPase, leading to the generation of a proton electrochemical gradient that drives H+/solute symport. By using pBR322 as vector and Escherichia coli as host, a fragment of S. typhimurium DNA coding for the phosphoglycerate transport system has been cloned. E. coli membrane vesicles containing the phosphoglycerate transport system also catalyze transport in the presence of phosphoenolpyruvate when they are loaded with pyruvate kinase and ADP. PMID- 6267593 TI - Poliovirus replication proteins: RNA sequence encoding P3-1b and the sites of proteolytic processing. AB - A partial amino-terminal amino acid sequence of each of the major proteins encoded by the replicase region (P3) of the poliovirus genome has been determined. A comparison of this sequence information with the amino acid sequence predicted from the RNA sequence that has been determined for the 3' region of the poliovirus genome has allowed us to locate precisely the proteolytic cleavage sites at which the initial polyprotein is processed to create the poliovirus products P3-1b (NCVP1b), P3-2 (NCVP2), P3-4b (NCVP4b), and P3-7c (NCVP7c). For each of these products, as well as for the small genome linked protein VPg, proteolytic cleavage occurs between a glutamine and a glycine residue to create the amino terminus of each protein. This result suggests that a single proteinase may be responsible for all of these cleavages. The sequence data also allow the precise positioning of the genome-linked protein VPg within the precursor P3-1b just proximal to the amino terminus of polypeptide P3-2. PMID- 6267594 TI - Eukaryotic DNA topoisomerases: two forms of type I DNA topoisomerases from HeLa cell nuclei. AB - Two type I DNA topoisomerases have been purified to homogeneity from the nuclei of HeLa cells. One topoisomerase has a peptide molecular weight of 100,000 and the other, a molecular weight of 67,000. Several lines of evidence indicate that these two topoisomerases are closely related, (a) Both exhibit similar enzymatic activities on DNA. (b) The chromatographic properties of the two topoisomerases during purification are similar. (c) Mild proteolysis of the purified molecular weight 100,000 topoisomerase in vitro generates a group of protein bands of molecular weight approximately 67,000, and these bands retain topoisomerase activity. (d) The peptides formed by partial proteolysis of the 67,000 topoisomerase in the presence of NaDodSO4 form a subset of those produced from the 100,000 enzyme. The 100,000 topoisomerase is the major type I enzyme in the cell. The 67,000 topoisomerase, which may be identical to the previously identified "nicking-closing" enzyme [Champoux, J. J. & Dulbecco, R. (1972) Proc. Natl. Acad. Sci. USA 69, 143-146], is probably formed by proteolysis of the 100,000 enzyme. PMID- 6267595 TI - Degradative inactivation of cyclic AMP-dependent protein kinase by a membranal proteinase is restricted to the free catalytic subunit in its native conformation. AB - A membranal proteinase from brush-border epithelial cells of the rat small intestine was shown to bring about a restricted and limited degradation of the free catalytic subunit (C) of cyclic AMP-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37) with concomitant inactivation of the kinase. This membranal proteinase exhibits a remarkable specificity. (i) It degrades C in its native conformation, but not after it has been heat-denatured. (ii) The degradation of C (Mr 40,000) does not proceed further, once a distinct clipped product (Mr 34,000) is formed. (iii) The undissociated ("stored") form of the enzyme (R2C2) is not attacked by the membranal proteinase, preserving both its potential catalytic activity and its molecular integrity. Only upon addition of cyclic AMP to release free C does the proteinase attack it. (iv) The membranal proteinase does not degrade the regulatory subunit (R), released by cyclic AMP from R2C2, although R is quite susceptible to degradation by other proteolytic enzymes. None of these features of the membranal proteinase could be reproduced with trypsin, chymotrypsin, clostripain, or papain. The specific, restricted, and limited action of this membranal enzyme raises the possibility that it may have a distinct physiological assignment associated with the bioregulation of cyclic AMP dependent protein kinase. PMID- 6267596 TI - Stable chromosomal integration of the entire nitrogen fixation gene cluster from Klebsiella pneumoniae in yeast. AB - A bacterial plasmid containing the entire nitrogen fixation (nif) gene cluster (consisting of at least 15 genes) from Klebsiella pneumoniae was used in conjunction with an Escherichia coli-yeast shuttle plasmid containing the yeast his4 gene cluster to cotransform a his4- recipient strain of Saccharomyces cerevisiae. Of 87 histidine-independent clones screened, 2 contained nif DNA. Restriction and hybridization analyses showed that two copies of the nif plasmid (46 kilobases each) are integrated in tandem in the recipient chromosome by recombination between homologous regions in the transforming plasmids. Chromosomal integration was also verified by tetrad analysis, showing that the nif DNA behaved in meiosis like a Mendelian element. During mitotic growth, one of the two copies of the nif region is frequently lost. The remaining copy of nif is stable, even after 40 generations in nonselective medium. PMID- 6267597 TI - Cloning a cDNA for the pro-alpha 2 chain of human type I collagen. AB - Poly(A)-RNA enriched for type I procollagen sequences was isolated from normal human fibroblasts and used as template to synthesize double-stranded cDNA with avian myeloblastosis virus (AMV) reverse transcriptase. After the ends had been blunted with nuclease S1 and dGMP tails had been added with terminal deoxynucleotidyltransferase, the double-stranded cDNA was annealed with pBR322 DNA that had previously been cleaved with EcoRI, blunted with AMV reverse transcriptase, and dCMP-tailed with terminal deoxynucleotidyltransferase. The chimeric molecule was used to transform Escherichia coli strain HB101. Ninety five recombinant clones were obtained and screened by dot hybridization analysis using 32P-labeled cDNA synthesized from the original poly(A)-RNA collagen enriched population. Three positive clones were isolated and further characterized by blot hybridization techniques and by EcoRII digestion. One clone with an insert of 2.2 kilobases was shown to contain sequences encoding for the pro-alpha 2 chain of human type I procollagen. DNA sequence analysis of a 172 nucleotide fragment demonstrated that the cloned cDNA extends from amino acid position 450 of the alpha 2 chain to the middle of the COOH-terminal propeptide. PMID- 6267598 TI - Mosaic nonequilibrium thermodynamics describes biological energy transduction. AB - A procedure, called "mosaic nonequilibrium thermodynamics," for describing ion movement and energy transduction in biological membranes is tested in a model system: bacteriorhodopsin liposomes. The important steps in the theoretical derivations are summarized; one of the experimental tests of the postulated fundamental flow-force relationships is shown. Furthermore, how the quantitative method, even if used only qualitatively, facilitates analysis and understanding of experimental results (in this case, the effect of medium composition on the development of pH gradient and membrane potential in the bacteriorhodopsin liposomes) is shown. The main advantage of this method lies in its quantitative description of the effect of variation of system parameters on the performance of, in this case, the reconstituted proton pump bacteriorhodopsin. As an example, the method is shown to explain quantitatively the dependence of the steady-state pH gradient on the light intensity. Even in more refined analyses of experiments, the quantitative theoretical description is in full accordance with the experimental results; this is illustrated by considering the effect of valinomycin on the dependence of the initial rate of proton uptake into bacteriorhodopsin liposomes on light intensity. It is concluded that mosaic nonequilibrium thermodynamics describes ion movement and energy transduction in the model system of bacteriorhodopsin liposomes and, therefore, may be applied to any other biological system performing such processes. PMID- 6267599 TI - Agonist-activated ionic channels in acetylcholine receptor reconstituted into planar lipid bilayers. AB - Planar lipid bilayers were formed with the mixed chain phospholipid 1-stearoyl-3 myristolglycero-2-phosphocholine. Acetylcholine receptor membrane fragments or the purified receptor protein was incorporated into these bilayers by fusing receptor-containing vesicles with the planar membranes a few degrees below the lipid phase transition temperature. Single-channel currents activated by nicotinic agonists in the reconstituted system resembled those observed in intact rat and frog muscle membrane as measured by the patch clamp technique. The observed channel characteristics did not depend on the degree of receptor purification. Thus, the receptor-enriched fragments and those depleted of nonreceptor peripheral peptides, the purified receptor monomer/dimer mixtures, and the isolated receptor monomer as defined by gel electrophoresis all shared similar electrochemical properties in the synthetic lipid bilayer. The agonist activated ionic channel seems, therefore, to be contained within the receptor monomer. PMID- 6267600 TI - Differential effects of transforming avian RNA tumor viruses on avian macrophages. AB - Functionally differentiated chicken macrophages were derived by in vitro differentiation of embryonic yolk sac cells and were characterized by several macrophage-specific cell markers. Uniform, infected, virus-producing cultures were obtained after exposure of these macrophages to avian myoblastosis virus (AMV), avian myelocytomatosis virus (MC29), myeloblastosis-associated virus (MAV 2), and Prague strain of Rous sarcoma virus (PR-B RSV). Both AMV and MC29 induced morphological transformation typical of the in vivo leukemias induced by these virus strains. Analysis of the expression of macrophage-specific markers in these two transformed cell types demonstrated that different markers of the mature macrophage were suppressed by each virus, even though the parental cell immediately preceding the transformation event was a mature macrophage in both cases. Cells infected with PR-B RSV and MAV-2 showed no observable difference from uninfected macrophages in terms of morphological characteristics, growth rate, or expression of the differentiated functions of macrophages. Ths system provides demonstrations of a cell type that produces infectious, transforming RSV but fails to respond by functional alterations induced by the transforming gene, src. PMID- 6267601 TI - DNA double-strand breaks induced in normal human cells during the repair of ultraviolet light damage. AB - DNA double-strand breaks (DSBs) are formed in normal human IMR-90 cells during repair incubation after 100 and 300 J.m-2 of ultraviolet light. By contrast, no DSBs are formed after exposure to ultraviolet light in human XPA cells (from a patient with xeroderma pigmentosum complementation group A), which are unable to excise pyrimidine dimers. The DSBs are not due to immediate cell death, because all the cells excluded trypan blue at the time of assay and because XPA cells, which are much more sensitive to ultraviolet light than are IMR-90 cells, did not form DSBs after exposure to ultraviolet light. The DSBs do not appear to be due to either DNA synthesis or cellular single-strand endonucleases. We suggest that repair-induced DSBs would be potent lesions that might lead to cytotoxicity, chromosome aberrations, deletion mutations, and perhaps cellular transformation. PMID- 6267602 TI - Ciliary membrane vesicles of paramecium contain the voltage-sensitive calcium channel. AB - Calcium influx into ciliary membrane vesicles from paramecia was measured by using arsenazo III as metallochromic indicator and as intravesicular calcium trap. Influx was rapid and reversible. In ciliary membrane vesicles from paramecium pawn mutants which lack the voltage-sensitive calcium channel, calcium influx was significantly less than in wild-type paramecia. These data demonstrate that the voltage-dependent calcium channel of paramecia is functional in a cell free system and available for biochemical studies. PMID- 6267603 TI - Estimation of genetic variation at the DNA level from restriction endonuclease data. AB - We consider the estimation of the genetic variation in a natural population when the data are obtained by the use of restriction endonucleases. Under the restriction endonuclease technique, a particular DNA segment is considered and cut wherever a recognition sequence appropriate to the endonuclease occurs. We consider data generated when a random sample of homologous DNA segments is treated in this way with one or a battery of restriction endonucleases. The numbers and sizes of the fragments that result indicate the locations and the frequencies of the recognition sequence (or, with a battery of restriction endonucleases, of each recognition sequence). These frequencies in the sample form the basis for an estimate of the amount of genetic variation in the population. PMID- 6267604 TI - Identification of the dnaQ gene product and location of the structural gene for RNase H of Escherichia coli by cloning of the genes. AB - By in vitro recombination we have constructed hybrid plasmids capable of complementing a conditional lethal mutator mutation, dnaQ49, in Escherichia coli K12. The dnaQ+ plasmids consist of a full-length pBR322 DNA and a 1.5-kilobase DNA fragment derived from the E. coli chromosome. Specific labeling of plasmid encoded proteins by the maxicell method revealed that the 1.5-kilobase insert codes for two proteins, one whose molecular weight is 25,000 [the 25-kilodalton (kDal) protein] and the other whose molecular weight is 21,000 (the 21-kDal protein). Because insertion of gamma delta sequence into the dnaQ gene of the plasmid resulted in disappearance of the 25-kDal protein, it was concluded that the 25-kDal protein is the dnaQ gene product. The 21-kDal protein was identified as RNase H on the basis of the following evidence. (i) Cells harboring the dnaQ+ plasmids, with or without the gamma delta insertion in the dnaQ gene, had a 5- to 7-fold higher level of RNase H activity than cells harboring pBR322. (ii) After induction of cells that are lysogenized with dnaQ+-transducing lambda phages, RNase H activity increased considerably. A similar high level of RNase H activity was observed with transducing phages whose dnaQ function was inactivated by insertion of a transposon, Tn3, into the gene, (iii) The plasmid-encoded RNase H, labeled with [35S]methionine, was purified in a manner essentially similar to that of the chromosome-encoded enzyme. These results suggest that the dnaQ gene and the structural gene for RNase H, termed gene rnh, are closely linked and located at 5 min on the linkage map. PMID- 6267605 TI - Production of antigen-specific suppressive T cell factor by radiation leukemia virus-transformed suppressor T cells. AB - Hen egg-white lysozyme (HEL)-specific suppressor T cells induced in C57BL/6 mice have been selected by sequential passage over plates coated with goat anti-mouse Ig and HEL. These suppressor T cells, 80% I-J+, were infected in vitro with radiation leukemia virus (RadLV/Nu1) and injected intravenously into sublethally irradiated syngeneic recipients. After 4-6 months, 6 out of 20 injected mice developed thymic lymphomas, which were maintained by transplantation into histocompatible hosts and subsequently established as permanent cell lines. Cells of these six thymomas were screened for the presence of Thy 1.2, Lyt 1, Lyt 2, I Jb, and Ig cell surface antigens by direct or indirect immunofluorescence. One tumor (thymoma L4) was found to express the expected phenotype of suppressor T cells (Thy 1.2+, Lyt 2+, I-J+). High-speed supernatants of extracts obtained from L4 cells were able to induce HEL-specific suppression in a T cell proliferative assay, demonstrating the presence of an antigen-specific suppressive T cell factor. PMID- 6267606 TI - Physical linkage of the constant region genes for immunoglobulins lambda I and lambda III. AB - During differentiation from a stem cell to an antibody-secreting cell, the immunoglobulin genes within a B cell undergo a rearrangement that juxtaposes a variable region gene to a constant region gene. To analyze the genetic organization of an immunoglobulin gene family in nonrearranged, germ-line DNA, we have constructed a recombinant DNA library from randomly cleaved mouse kidney DNA fragments. From this library, we have isolated three overlapping recombinant clones containing the constant region gene for lambda I light chains (C lambda I). These clones spanned 24.9 kilobases of mouse DNA and contained no variable region sequences. Hybridization of these clones with lambda II cDNA demonstrated the presence of an additional constant region gene and a joining region 3.2 kilobases 5' of C lambda I. This gene was tentatively identified as C lambda III by the absence of an Ava I endonuclease site, which is present within C lambda II. The C lambda III amino acid sequence has recently been reported [Azuma, T., Steiner, L. A. & Eisen, H. N. (1981) Proc. Natl. Acad. Sci. USA 78, 569-573] and is very closely related to the C lambda II amino acid sequence. PMID- 6267607 TI - Immunochemical delineation of an oncofetal antigen on normal and simian virus 40 transformed human fetal melanocytes. AB - Human melanoma cells of uveal origin shed 94,000- and 240,000-dalton glycoproteins in common with most melanoma cell lines of dermal origin. Normal human melanocytes derived from fetal uvea shed a 90,000-dalton glycoprotein that was found to be immunologically identical with the 94,000-dalton glycoprotein of melanoma cells. Expression of this 90,000-dalton molecule was confined to fetal cells of ectodermal origin. After simian virus 40 (SV40) transformation of human fetal melanocytes, there was an apparent increase in molecular size of this component to 94,000 daltons. In contrast, the 240,000-dalton glycoprotein was not synthesized or shed by uninfected or SV40-transformed fetal melanocytes. These data suggest that the 94,000-dalton glycoprotein is an oncofetal antigen of ectodermal origin. PMID- 6267608 TI - Leukotrienes promote plasma leakage and leukocyte adhesion in postcapillary venules: in vivo effects with relevance to the acute inflammatory response. AB - Leukotrienes B4, C4, and D4, members of a recently discovered family of substances biosynthesized from arachidonic acid, were found to have potent microvascular actions in the hamster cheek pouch. When applied topically to the vascular network, leukotrienes C4 and D4 caused an intense constriction of arterioles, being similar to angiotensin in potency in this respect. The vasoconstriction induced by leukotrienes C4 and D4 was short-lived, and it was consistently followed by a marked and dose-dependent extravasation of macromolecules from postcapillary venules. Histamine did not constrict arterioles, but it elicited leakage of plasma, although on a molar basis it was no more than 1/1000th as potent as the leukotrienes. When used in the same concentration range as leukotrienes C4 and D4, leukotriene B4 did not evoke vasoconstriction or promote plasma leakage. On the other hand, leukotriene B4 caused a conspicuous and reversible adhesion of leukocytes to the endothelium in postcapillary venules. Our findings that leukotrienes induce microcirculatory alterations in vivo, closely resembling the early events in the acute inflammatory response, imply that leukotrienes, formed in several blood-borne and tissue-bound cells, may mediate important microcirculatory adjustments to noxious stimuli. PMID- 6267609 TI - State of hepatitis B virus DNA in hepatocytes of patients with hepatitis B surface antigen-positive and -negative liver diseases. AB - Using the Southern blot technique and cloned hepatitis B virus (HBV) DNA as a probe, we studied the state of HBV DNA in the liver of 13 patients with hepatocellular carcinoma, 17 patients with chronic hepatitis, and 2 patients with acute hepatitis. The hybridization results were compared with the serological and immunohistological data. Integration of HBV DNA in cellular DNA of the liver from patients with hepatocellular carcinoma was demonstrated. In two patients from which tumorous and nontumorous liver tissue samples were available the integration patterns were different. In one patient with hepatitis B e antigen (HBeAg)-positive early hepatocellular carcinoma, free viral DNA was present in the liver. In some patients with HBeAg-negative chronic hepatitis, without tumor, integration of HBV DNA in cellular DNA was also demonstrated. This suggests that HBV is not the only factor involved in the development of a tumor. In patients with HBeAg-positive chronic hepatitis, free viral DNA was detected in the liver. In the two acute hepatitis patients analyzed, the restriction endonuclease patterns strongly suggested HBV DNA integration. Therefore, viral DNA integration seems to occur early in infection. Whatever the form of the disease, discrete bands were observed, suggesting the existence of limited and specific integration sites in host cellular DNA. The presence of integrated or free DNA sequences has implications for antiviral therapy. In addition, detection of HBV DNA in the liver is another sensitive viral marker that could be useful for diagnostic purposes. PMID- 6267610 TI - Benzodiazepines have high-affinity binding sites and induce melanogenesis in B16/C3 melanoma cells. AB - We found that two markers of differentiation, tyrosinase (monophenol, dihydroxyphenylalanine:oxygen oxidoreductase, EC 1.14.18.1) activity and melanin synthesis, are induced by diazepam in B16/C3 mouse melanoma cells. We also demonstrated high-affinity binding sites for [3H]diazepam in these cells by radioreceptor assay, and we visualized binding to the cell surface by fluorescence microscopy with a benzodiazepine analog conjugated to a fluorescein labeled protein. Our studies also showed that there are differences between the binding characteristics in intact cells and in membrane fractions prepared from these cells. Scatchard analysis of the binding data from membrane fractions gave a linear plot (Kd = 9.1 X 10(-8) M). With intact cells, a curvilinear Scatchard plot was obtained. This was resolved into two components defining binding sites with affinity constants of 1.7 X 10(-9) M and 4.6 X 10(-7) M. Thus, it appears that [3H]diazepam binding in intact cells is more complex than in isolated membranes. Several related benzodiazepines, including flunitrazepam, Ro-5-4864, nitrazepam, oxazepam, lorazepam, Ro-5-3072, chlordiazepoxide, and clonazepam also induced melanogenesis. When these compounds were tested for their ability to inhibit [3H]diazepam binding, flunitrazepam, diazepam, and Ro-5-4864 were found to be the most effective inhibitors. These three compounds were also the most potent in inducing melanogenesis. Our results suggest that the benzodiazepines modulate cell differentiation. The presence of high-affinity binding sites in this homogeneous, easily grown cell line may provide a useful model for studies on the mechanism of action of these compounds. PMID- 6267611 TI - Histidine modification with diethyl pyrocarbonate shows heterogeneity of benzodiazepine receptors. AB - The effect of diethyl pyrocarbonate modification of histidine on the specific binding of [3H]diazepam and its enhancement with muscimol and (+/-)-pentobarbital was investigated. Diethyl pyrocarbonate treatment produced a dose-related inhibition of specific [3H]diazepam binding to rat brain membranes with a maximal inhibition of approximately 40% at 1 mM. Scatchard analysis of the binding data showed that diethyl pyrocarbonate, while having no effect on the affinity (Kd), decreased the binding capacity (Bmax) of diazepam from a control value of 1543 +/ 116 fmol/mg of protein to 789 +/- 79 fmol/mg of protein (mean +/- SD; P less than 0.005; n = 4). Under conditions in which approximately 40% of the diazepam binding sites were modified by diethyl pyrocarbonate treatment, the ability of muscimol and pentobarbital to enhance diazepam binding was not altered. These results suggest that a histidine residue is critical for a part (approximately 40%) of the benzodiazepine binding sites and that there may exist a heterogeneity of benzodiazepine binding sites. Furthermore, these results indicate that perhaps only a portion of the benzodiazepine binding sites are functionally coupled to the gamma-aminobutyric acid receptor-ionophore complex. PMID- 6267612 TI - Rapid recovery of function after partial denervation of the rat pineal gland suggests a novel mechanism for neural plasticity. AB - The activity of serotonin N-acetyltransferase (NATase) in the rat pineal gland exhibits a large (approximately 100-fold) circadian variation, with peak activity occurring in the dark part of the light/dark cycle. Surgical removal of both superior cervical ganglia abolishes this rhythm in enzyme activity. Unilateral ganglionectomy caused a 75% decrease in NATase activity during the dark period immediately following the operation; however, by the subsequent dark period (32 hr after operation) the rhythm in NATase activity had returned to normal. Similar results were found after the internal carotid nerve was cut, and data are presented indicating that this is the postganglionic trunk by which sympathetic neurons reach the pineal gland. Denervation of one superior cervical ganglion (unilateral "decentralization") also produced a 75% decrease in NATase activity during the dark period immediately following the operation; however, after decentralization, enzyme activity did not return to normal in subsequent cycles. It is hypothesized that this recovery is due to loss of norepinephrine uptake sites in the degenerating sympathetic nerve terminals. As a result of decreased norepinephrine uptake, the effectiveness of the norepinephrine released by surviving neurons may be enhanced. This hypothesis is supported by experiments in which pharmacological blockade of norepinephrine uptake in unilaterally decentralized animals increased NATase activity to control levels. We propose that neural systems which use transmitter uptake as the mechanism of transmitter inactivation have a built-in "reserve stimulatory capacity." PMID- 6267613 TI - Cyclic GMP releases calcium from disc membranes of vertebrate photoreceptors. AB - Physiological concentrations of cyclic guanosine 3',6'-monophosphate (cGMP) inhibit 45Ca uptake and increase 45Ca release from vertebrate photoreceptor rod outer segment disc membranes. These effects are specific for cGMP. Several facts, including the independence of these effects from added triphosphates, suggest that cGMP diminishes the Ca-binding capacity of the disc membranes. Preliminary data show that the apparent affinity constant of the cGMP-dependent Ca-binding sites of the disc membranes is of the same (or even higher) order of magnitude as that of ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. As expected, the observed cGMP effects are not dependent on the light or dark conditions of the disc membranes. PMID- 6267614 TI - Characterization of specific receptors for calcitonin in porcine lung. AB - The binding of salmon calcitonin was investigated in subcellular fractions obtained from normal porcine lung. Only the membrane fraction (density, 1.14 g/cm3) showed specific binding for calcitonin. Specific binding of 125I-labeled salmon calcitonin was competitively inhibited by concentrations of unlabeled homologous hormone in the range 0.01-1 nM. Half-maximal inhibition of binding was observed with 0.12 nM salmon calcitonin. Scatchard analysis of the data suggested the presence of one class of binding sites with a mean affinity constant of 0.9 X 10(10) M-1 and a mean receptor number of 40 X 10(8)/mg of protein. The binding of salmon calcitonin was highly specific; half-maximal inhibition of binding was observed with 63.8 nM bovine calcitonin, the hormone corticotropin having no effect in this system. PMID- 6267615 TI - The biology of superoxide and of superoxide dismutases - in brief. PMID- 6267616 TI - Inherited biochemical defects in lymphocytes causing immunodeficiency disease. PMID- 6267617 TI - Pivmecillinam plus pivampicillin in urinary tract infections: a randomized, open comparison with co-trimoxazole in hospitalized patients. AB - The efficacy and tolerance of a fixed-dose combination of 200 mg pivmecillinam and 250 mg pivampicllin was compared with that of co-trimoxazole (800 mg sulphamethoxazole plus 160 mg trimethoprim) in 42 hospital in-patients with complicated urinary tract infections. Patients received a 10-day course of tablets of either agent twice daily. The infecting organisms, which were Enterobacteriaceae (79%) and enterococci (21%), were eradicated in 17(89%) of the 19 patients given co-trimoxazole and in all 23 subjects who received pivmecillinam/pivampicillin. Sixteen (89%) of the 18 symptomatic patients responded clinically to co-trimoxazole. Pivmecillinam/pivampicillin was effective in 19 (95%) of 20 patients with symptomatic infections. There was a fairly good correlation between the bacteriological and clinical responses. No serious side effects were recorded and all patients completed the prescribed course of treatment. PMID- 6267618 TI - Presynaptic regulation of the release of catecholamines. AB - During norepinephrine release elecited by the arrival of nerve impulses, the neurotransmitter interacts with specific receptors (alpha1-, beta1-, beta2 adrenoceptors) located in the membrane of the postsynaptic cell to trigger the response of the effector organ. Until a few years ago, it was thought that the role of noradrenergic nerve terminals in neurotransmission is concerned exclusively with the synthesis, storage, release, and inactivation of norepinephrine and there were no indications that receptors might also be present in the presynaptic membrane. During the last decade, evidence has accumulated in favour of the view that, in addition to the classical postsynaptic adrenoceptors that mediate the responses of the effector organ, there are also receptors located on the noradrenergic nerve terminals. These presynaptic recptors are involved in the modulation of the calcium-dependent, action-potential-evoked release of norepinephrine in the peripheral as well as in the central nervous system. Presynaptic inhibitory alpha-adrenoceptors are involved in the regulation of the release of norepinephrine through a negative feedback mechanism mediated by the neuron's own transmitter. Alpha-Adrenoceptor agonists inhibit the release of norepinephrine during nerve stimulation, while alpha-adrenoceptor blocking agents enhance the stimulation-evoked release of the neurotransmitter. These results have been obtained both i vitro and in vivo. There are pharmacological differences between the postsynaptic alpha-adrenoceptors that mediate the response of the effector organ and the presynaptic inhibitory alpha-adrenoceptors that modulate the release of norepinephrine during nerve stimulation. The subclassification of alpha-adrenoceptors into alpha1- and alpha2-types is bases on differences in relative affinities for a range of alpha-adrenoceptor agoinst and antagonist durgs. The term alpha1-adrenceptor is used for a receptor that is preferentially stimulated by phenylephrine and blocked by prazosin, whereas alpha2-adrenoceptor is reserved for those preferentially stimulated by guanabenz or clonidine and blocked by rauwolscine or yohimbine. The presynaptic inhibitory alpha-adrenoceptors in the peripheral and in the central nervous system have the pharmacological characteristics of the alpha2-adrenoceptors. Presynaptic inhibiotry autoreceptors appear to be involved in the modulation of the release of dopamine and of epinephrine in the central nervous system. A short negative feedback mechanism similar to that for norepinephrine appears to regulate the stimulation-evoked release of dopamine and epinephrine in central neurons. In addition to presynaptic autoreceptors through which the transmitter can modulate its own release, a real mosaic of receptors in present on noradrenergic nerve endings... PMID- 6267619 TI - The influence of fragments of the LPH chains on learning, memory and attention in animals and man. PMID- 6267620 TI - Biosynthesis and control of secretion of corticotropic, lipotropic and melanotropic peptides. PMID- 6267621 TI - Lack of postulated opiate-receptor antagonistic properties of compound 48/80. AB - The previously suggested opiate-receptor antagonistic properties of compound 48/80 were checked both in vivo and in vitro. In electrically stimulated guinea pig ileum and rat vas deferens preparations compound 48/80 did not reverse the inhibition of the twitches caused either by morphine or Met5-enkephalin. In mice hot-plate test compound 48/80 did not decrease the analgesic activity of morphine. In radioreceptor studies compound 48/80 shows rather low affinity to the 3H-naloxone receptor sites from striatal homogenates of the rat, as compared to non-labelled naloxone and on the other hand it produced moderate, as compared to d-butaclamol, displacement of 3H-spiroperidol from rat striatal homogenates. The variation of composition of various polymers making compound 48/80 is suggested for explanation of obtained results. PMID- 6267622 TI - The effect of metabolic inhibitors on the large plaque effect with Herpes simplex virus. PMID- 6267623 TI - The effect of ultraviolet light on the cyclic nucleotide system of human fibroblasts. PMID- 6267624 TI - Post-learning paradoxical sleep, reticular activation and noradrenergic activity. PMID- 6267625 TI - Feeding elicited by injection of the cholecystokinin antagonist dibutyryl cyclic GMP into the cerebral ventricles of sheep. PMID- 6267626 TI - Suppression of wet-dog shakes by tail and scruff-pinch. PMID- 6267627 TI - Sexually dimorphic acquisition of a conditioned taste aversion in rats: effects of gonadectomy, testosterone replacement and water deprivation. PMID- 6267628 TI - Refractory periods and anatomical linkage of the substrates for lateral hypothalamic and periaqueductal gray self-stimulation. PMID- 6267629 TI - Quantitative analysis of the lipid-mobilizing effects of corticotropin, beta 1-24 -corticotropin (tetracosactide) and isoprenaline in older rats and rabbits. AB - The lipid mobilizing effects of corticotropin (ACTH), beta 1-24-corticotropin tetracosactide (TCA) and isoprenaline (ISO) were studied in parallel experiments in older rabbits (six months, weight 3.5 kg) and rats (age 75-85 days, weight 275 g) in vitro. The results were analysed quantitatively. Compared with the effect in younger rats the lipid mobilizing action of ISO in older animals does not differ. The same applies to the very low ISO lipolytic potency in rabbits. The ACTH intrinsic activity and affinity decrease in aging rabbits, but not in aging rats. At the concentration 1 x 10(-9) mol/l of TCA 35% of its maximum effect is reached in rabbits and almost the maximum in rats. In comparison with the maximum response to ACTH the maximum of TCA is two times higher in rabbits whereas in rats it reaches only 80% of the ACTH maximum. The order of the intrinsic activities is in older rats and rabbits different: ISO much greater than ACTH greater than TCA (1.00:0.81:0.64) in rats and TCA greater than ACTH greater than ISO (1.00:0.53:0.31) in rabbits. The affinity relations TCA greater than ISO greater than ACTH are identical in both species with the ratios of ACTH:ISO:TCA = 1:50:1740 in rats and 1:34:915 in rabbits. TCA exerts the strongest lipolytic potency in rats which is 5.5 times greater than in rabbits. On the contrary the intrinsic activity of TCA in rabbits is the highest. In older rabbits the ACTH adipokinetic intrinsic activity and affinity decrease faster than those in ISO. The species differences especially in relation to ISO also remain preserved in older animals and this applies to the TCA lipolytic effects, which in turn do not seem to change with aging as much as the effects of ACTH. When evaluating the species differences or the sensitivity changes connected with aging in the action of lipolytic drugs, the intrinsic activity and affinity should be considered separately. PMID- 6267630 TI - Analysis of two chloramphenicol resistance plasmids from Staphylococcus aureus: insertional inactivation of Cm resistance, mapping of restriction sites, and construction of cloning vehicles. PMID- 6267631 TI - Analysis of chromosome mobilization using hybrids between plasmid RP4 and a fragment of bacteriophage lambda carrying IS1. PMID- 6267632 TI - Tn554: isolation and characterization of plasmid insertions. PMID- 6267633 TI - Physical characterization of plasmids from Streptomyces kasugaensis MB273. PMID- 6267634 TI - The use of restriction endonucleases to compare mitochondrial DNA sequences in Mus musculus: a detailed restriction map of mitochondrial DNA from mouse L cells. PMID- 6267635 TI - Transcription of kinetoplast DNA in Trypanosoma brucei bloodstream and culture forms. PMID- 6267636 TI - Inhibition of platelet aggregation by 6-keto-PGE1; lack of an effect on cyclic GMP levels. AB - The effects of 6-keto-PGE1 on aggregatory responses to arachidonic acid (AA), adenosine diphosphate (ADP) and collagen were studied in human platelet-rich plasma (PRP). In addition, experiments were carried out to determine if these effects correlate with changes in platelet cyclic AMP and cyclic GMP levels. 6 Keto-PGE1 incubated in PRP produced dose-related increases in platelet cyclic AMP levels whereas platelet cyclic GMP levels were unchanged. Control aggregations induced by AA and ADP did not alter cyclic AMP and cyclic GMP levels whereas control aggregations induced by collagen elevated cyclic GMP levels with cyclic AMP were unchanged. 6-Keto-PGE1 produced a dose-dependent inhibition of platelet aggregation induced by AA, ADP and collagen and this inhibition correlated with a dose-related increase in cyclic AMP levels. Since 6-keto-PGE1 does not consistently alter cyclic GMP levels in human PRP, the present data support previous studies suggesting that 6-keto-PGE1 produces inhibition of platelet aggregation through the stimulation of cyclic AMP accumulation. PMID- 6267637 TI - Studies of the renal vasoactive systems in hyporeninemic hypoaldosteronism. AB - Plasma renin activity, total renin, active renin, and aldosterone were measured as well as urinary prostaglandin E2 and kallikrein in a group of patients with hyperkalemia (6.1-7.7 mEq per liter) and hyporeninemic hypoaldosteronism. Plasma renin activity and aldosterone were low and the response was markedly blunted to upright posture, and furosemide. The rise in cortisol but not aldosterone was normal following ACTH stimulation. Active renin was depressed; however, total renin was normal. Urine PGE was variable including some low values, but the mean of the group was normal (p greater than 0.1). Urine kallikrein excretion was markedly diminished and undetectable in most cases. Fludrocortisone normalized potassium but minimally increased kallikrein in the patients. The possibility exists that kallikrein deficiency in these patients may underlie the inability to generate active renin. PMID- 6267638 TI - Transformation of arachidonic acid in leukocytes. Isolation and structural analysis of a novel dihydroxy derivative. PMID- 6267639 TI - Inhibition of serum oxytocinase activity by prostaglandins. AB - The effect of prostaglandins (PGs) and other compounds on human serum oxytocinase (EC 3.4.11.3) activity in vitro was studied by a sensitive assay using S-benzyl-L cysteine-p-nitroanilide as substrate. PGE1, PGE2 and PGF2 alpha significantly inhibited serum oxytocinase activity in a dose-related manner and in decreasing order of potency. cGMP, 8-bromo-cGMP, indomethacin, polyphloretin phosphate, hypertonic saline and urea were also active. cAMP, db-cAMP, 8-bromo-cAMP, db cGMP, 5'-AMP, 5'-ADP, 5'-ATP, 5'-GDP, 5'-GTP, aspirin, sodium salicylate, paracetamol, theophylline and IBMX did not inhibit the enzyme activity. The results suggest that the oxytocic action of prostaglandins may be due, at least in part, to an inhibition of oxytocinase activity. PMID- 6267640 TI - Effect of epinephrine on prostaglandin E2 and cyclic AMP levels in gingiva of patients with chronic periodontitis. AB - The levels of prostaglandin E2 (PGE2) and cyclic AMP (cAMP) in human gingival samples were determined by means of radioimmunoassay after incubation with epinephrine (10(-6)M) at different time intervals. The levels of PGE2 and cAMP reached a maximum in the control and hormone treated samples after 80 and 40 minutes, respectively. Epinephrine seemed to affect a lesser increase in PGE2 and a greater increase in cAMP values in gingival tissues when compared with control samples. When the data were analysed, there was statistically significant differences found between the control and hormone treated samples regarding both PGE2 and cAMP. PMID- 6267641 TI - Neutrophil function in Bartter's syndrome. AB - Bartter's syndrome is a state associated with hyperprostaglandinemia and high urinary excretion of prostaglandin derivatives. Because of numerous reports on prostaglandins acting as local modulators of the immune system, we have studied parameters of phagocytic function and of cellular and humoral immunity in four patients with this disease. An augmentation in chemotaxis was identified in Bartter's syndrome neutrophils. Despite some minor deviations in other parameters measured, no other gross derangement in immune function could be identified. PMID- 6267642 TI - Defective genetic control of sodium-pump density in manic depressive psychosis. PMID- 6267644 TI - Testing cyclic AMP mediation of memory: reversal of alpha-methyl-p-tyrosine induced amnesia. AB - Treatments that increased intracellular cyclic 3',5' adenosine monophosphate (cAMP) levels following catecholamine depletion caused by alpha-methyl-p-tyrosine (AMPT) provided a prophylactic effect against AMPT-induced amnesia. This effect gives evidence that cAMP mediated the formation of memory. In Experiment I, the phosphodiesterase inhibitor papaverine (50 mg/kg), immediately after a one-trial acquisition task, functionally increased cAMP levels and prevented amnesia 3 h after treatment with AMPT (200 mg/kg) for New Zealand A strain (NZ/A) mice tested in a step-through passive avoidance apparatus. Retention test latencies 72 h later were significantly higher for animals that received only saline and for animals that received AMPT and papaverine than for animals that received AMPT and saline (the amnesic group). In a similar task (Experiment II), mice that received an intracerebroventricular injection of either 5 or 10 microgram dibutyryl cAMP immediately after acquisition and 3 h after AMPT administration showed significantly higher retention test latencies than animals that received AMPT and saline. The AMP plus 10 microgram dibutyryl cAMP group showed facilitated performance even compared to the saline plus saline group. PMID- 6267643 TI - Naloxone effects on beta-endorphin, cortisol, prolactin, growth hormone, HVA and MHPG in plasma of normal volunteers. AB - 8 mg of naloxone were administered IV to 14 normal volunteers in a placebo controlled, double-blind experiment. Plasma levels of beta-endorphin, cortisol, prolactin, growth hormone, HVA and MHPG were determined before and 45 min after administration. Naloxone elicited significant increases in cortisol and MHPG but did not change plasma levels of the other compounds. In an additional experiment on two subjects, 20 mg of naloxone caused elevations of beta-endorphin as well as of cortisol. This parallel increase indicates that the linkage between the secretion of beta-endorphin and ACTH/cortisol may be dose-dependent. The increase in MHPG is in agreement with the hypothesized association of noradrenergic hyperactivity and opiate withdrawal. PMID- 6267645 TI - Pre-exposure effects of morphine, diazepam and delta 9-THC on the formation of conditioned taste aversions. AB - Prior to taste aversion conditioning with morphine, diazepam or delta 9 tetrahydrocannabinol (delta 9-THC), rats received pre-exposures to the vehicle or one of the three drugs. Morphine pre-exposures blocked the aversion normally induced by morphine, but not by delta 9-THC or diazepam. Diazepam pre-exposures attenuated both the morphine- and diazepam-induced taste aversions to a significantly greater degree than the taste aversion induced by delta 9-THC. As a result of delta 9-THC pre-exposures, the aversions induced by diazepam and delta 9-THC were attenuated as well as the morphine-induced aversion, which was the most greatly attenuated. These results demonstrate that pre-exposure effects are not necessarily bi-directional and, moreover, they are inconsistent with current hypotheses which attempt to account for the attenuating effect of drug pre exposures on taste-aversion conditioning. PMID- 6267646 TI - alpha-Melanocyte stimulating hormone stimulates sexual behaviour in the female rat. PMID- 6267647 TI - Citalopram: a new potent inhibitor of serotonin (5-HT) uptake with central 5-HT mimetic properties. AB - Citalopram (1--16 mg/kg), but not amitriptyline, clomipramine, imipramine or zimelidine, stimulated the hind limb flexor reflex in the spinal rat. This stimulatory effect was abolished by serotonin (5-HT) receptor blocking agents (cyproheptadine, metergoline) and prevented ty p-chlorophenylalanine, an inhibitor of 5-HT synthesis. Citalopram (20 mg/kg), similarly but more strongly than clomipramine (20 mg/kg), prevented both fenfluramine- and p chloroamphetamine-induced hyperthermia in rats kept at 28 degrees C. In contrast to amitriptyline and imipramine, citalopram did not reduce the number of quipazine-induced head twitches in rats (ID50 greater than 50 mg/kg). Also, unlike the above mentioned antidepressants, it did not antagonize, but rather potentiated the 5-HT-mediated rise in blood pressure in pithed rats. The results obtained indicate that, unlike the presently known inhibitors of 5-HT uptake, citalopram considerably potentiates serotonergic transmission, possibly by producing very strong inhibition of uptake without simultaneous blockade of the postsynaptic 5-HT receptors. PMID- 6267648 TI - Clinical effects and plasma levels of delta 9-tetrahydrocannabinol (delta 9-THC) in heavy and light users of cannabis. AB - delta 9-Tetrahydrocannabinol (delta 9-THC) was administered in a crossover design by smoking and IV injection to groups of heavy and light users of marihuana. Plasma concentrations of delta 9-THC were similar for the groups after IV injection of 5.0 mg delta 9-THC, but the AUC0-240 min showed a trend towards lower values for the heavy user group. To achieve a maximum desired "high", both groups smoked similar amounts (about 13 mg) of delta 9-THC. Heavy users tended to have higher plasma levels than light users. The systemic availability of smoked delta 9-THC was significantly higher for the heavy users (heavy users 23 +/- 16% vs 10 +/- 7% for light users). These results also indicate that heavy cannabis users smoke more efficiently than casual smokers. Both light and heavy users showed more clinical effect following IV administration than after smoking. The response of the heavy users, both with respect to effect on heart and "high", was quite comparable to that of light users. The present study does not suggest that tolerance readily develops in heavy users. PMID- 6267649 TI - Modulation of rat brain alpha-adrenoreceptor populations four weeks after stimulation of the nucleus locus coeruleus. AB - We previously showed that electrical stimulation of the nucleus locus coeruleus was followed 4 weeks later by a greatly improved performance in the acquisition of a food-reinforced operant task. To ascertain whether adrenergic receptors were involved in this long-term behavioral modification, we studied the characteristics of the alpha 1, alpha 2, and beta-adrenoreceptors of the cerebral cortex 4 weeks after stimulation of the locus coeruleus. This stimulation induced a slight (14%) but significant increase in the number of alpha 1-receptor [(3H) WB 4101 binding sites] as well a rise in the number of alpha 2-receptor [(3H) clonidine binding sites]. The latter rise mainly affected high-affinity alpha 2 receptor sites (36%) and the number of low-affinity sites remained unchanged. No significant alteration in the number of beta-receptors [(3H)-dihydroalprenolol binding sites] was observed. To confirm this biochemical result, the effect of very small doses of clonidine (1, 2.5, 5 and 10 micrograms/kg) was tested on locomotor activity in the open-field. In rats stimulated 4 weeks before injection, clonidine induced a biphasic effect, comprising firstly sedation which occurred 30 min after injection, and secondly, long-term hyperactivity which began 24 h injection. For the 5 micrograms/kg dose, this rebound of activity was detectable 8 days after injection. In implanted, control rats, only the sedative effect was observed. These findings are interpreted in relation to the current theories about alpha-adrenoreceptors. PMID- 6267650 TI - Ethanol-induced changes of dopaminergic function in three strains of mice characterized by a different population of opiate receptors. AB - The effects of ethanol have been studied in three strains of mice (DBA 2J, albino, and C57 BL/6J) having different populations of opiate receptors. Acute ethanol treatment induces a significant increase in striatal dopamine metabolism only in the mouse strains (C57 and albino) that are rich in enkephalinergic receptors upon nigrostriatal dopaminergic fibers. After chronic ethanol, the same strains develop tolerance to striatal dihydroxyphenylacetic acid increase, while the striatal dopaminergic recognition sites become supersensitive. DBA mice, which have lower numbers of enkephalinergic receptors and higher levels of enkephalins in the striatum, fail to show changes in central dopaminergic function after acute or chronic ethanol treatment. Our results indicate the importance of an interaction between ethanol and opiate receptors in determining the neurochemical and behavioral effects of ethanol. PMID- 6267651 TI - Relationship among estrogen-induced psychophysiological changes in hypogonadal women. AB - Estrogen treatment of 16 hypogonadal women showed lessening of gonadotrophins, vasomotor symptoms, psychometrically measured aggression, and average sleep latency, but more Rapid Eye Movement sleep in a 100-day cross-over, double-blind comparison with placebo treatment. Of eight insomniac subjects, four showed decreased, but four showed increased insomnia scores and sleep latencies. Clinical rank of psychological intactness correlated with sleep latency and with total sleep time during the estrogen condition. Although estrogen altered both physiological and psychological states, such effects were characterized by different time courses and different degrees of consistency among the subjects. PMID- 6267652 TI - [Spectrophotometric assay of 5-phosphoribosyl-1-pyrophosphate synthetase (PRPP) in erythrocyte lysate (author's transl)]. PMID- 6267653 TI - Loss of covalently linked lipid as the mechanism for radiation-induced release of membrane-bound polysaccharides and exonuclease from Micrococcus radiodurans. PMID- 6267654 TI - The control of the heavy metals health hazard in the reclamation of wastewater sludge as agricultural fertilizer. PMID- 6267655 TI - Control of ciliary activity in Paramecium: an analysis of chemosensory transduction in a eukaryotic unicellular organism. PMID- 6267656 TI - [ACTH, endorphins and related peptides (author's transl)]. PMID- 6267657 TI - [Enzymes of neutrophils in aged persons (author's transl)]. PMID- 6267658 TI - [Effect of lithium chloride on carbohydrate metabolism in mice]. PMID- 6267659 TI - [Ultrasonography in primary hepatic tumors: potentialities, limits and comparison with arteriography (author's transl)]. AB - The echotomographic patterns in 22 patients with hepatic neoplasms are reported and discussed. Ultrasonography has a high sensitivity in detecting the solid echopattern of the tumour and its origin from liver parenchyma; gray-scale B scan and a meticulous technique are very helpful for this purpose. Echotomography plays an important part in the diagnostic evaluation of this pathology, to better select the patients for more invasive techniques, after the screening procedures, as scintigraphy. PMID- 6267660 TI - [Comments on a case of left-sided gallbladder]. PMID- 6267661 TI - The central nervous influence of drugs on intraocular pressure. PMID- 6267662 TI - [Clinical case of cylindroma]. PMID- 6267663 TI - [Malignant fibrous histiocytoma of bones: an important differential diagnosis of malignant bone neoplasms]. PMID- 6267664 TI - [Efficiency of diamond instruments in the abrasion of human dental enamel and glass. Preliminary test with nationally- and foreign-made instruments]. PMID- 6267665 TI - [Mediastinal neurogenic tumors]. AB - An analysis is presented of clinical, radiological and evolutive aspects of 106 neurogenic mediastinal tumors operated in the Clinic for Tjhoracic surgery from Bucharest. The predominance is stressed of tumours originating in the nervous sheaths (62%), and the high incidence of tumours of the nervous cells (sympatomas, ganglio-neuroblastomas) in children. An analysis is made of the various surgical aspects. and the post-operative results, mostly favourable in over 90% of the subjects that underwent surgery. PMID- 6267666 TI - [Malignant gastric ulcer. Apparent cure with medical treatment. Presentation of a case]. PMID- 6267667 TI - [Bone metastasis and hepatoma: clinical and prognostic significance]. PMID- 6267668 TI - [Anatomoclinical sessions of the Instituto Nacional de Oncologia]. PMID- 6267669 TI - Prostate cancer. Radiotherapy. PMID- 6267670 TI - Cardiovascular actions of angiotensin in the fowl (Gallus domesticus). II. Angiotensin analog agonists and antagonists. AB - Like angiotensin II (AII) itself, [SAR1] AII induced a biphasic blood pressure response in the conscious chicken--an initial depressor response followed by a pressor response. Angiotensin III, however, induced only a depressor response in the dose range tested. The response to angiotensin I was similar to that to AII, and appeared to be due to its conversion to AII as it was inhibited by prior infusion of the angiotensin converting enzyme inhibitor SQ 20,881. Two angiotensin analog antagonists [SAR1ALA8] AII and [SAR1ILE8] AII inhibited both components of the response to AII, but the pressor response was inhibited at lower concentrations of antagonist than was the depressor response. These findings give further support to the suggestion that the pressor and depressor component of the response to AII in the conscious chicken are mediated via different AII receptors, and indicate the possibility of selective blockade of these two components. PMID- 6267671 TI - Alpha- and beta-adrenergically mediated responses in isolated lung strips of guinea pigs. AB - Thin strips of lung parenchyma from guinea pigs were mounted in an isolated tissue bath and placed under an initial tension of 1.2 gm. Drug-induced changes in resting tension were recorded isometrically upon the addition of representative alpha- and beta-adrenergic agonists. Lung strips relaxed following challenge with isoproterenol, 10(-9) to 10(-6)M (beta-adrenergic agonist), and contracted following challenge with phenylephrine, 10(-6) to 10(-4)M (alpha adrenergic agonist). The responses of lung strips to norepinephrine, 10(-8) to 10(-4)M (mixed alpha- or beta-agonist) were influenced by the presence of either an alpha- or beta-adrenergic antagonist: pretreatment with phentolamine, 10(-5)M (alpha-antagonist) resulted in relaxant responses to norepinephrine, whereas pretreatment with propranolol, 10(-5)M (beta-antagonist) resulted in contractile responses. Cocaine, an uptake-1 inhibitor, potentiated the contractile effect of norepinephrine but not the relaxant effect of isoproterenol or norepinephrine. These data support the existence of alpha- and beta-adrenergic receptors mediating contraction and relaxation, respectively, in guinea pig lungs. PMID- 6267672 TI - Effect of 1 alpha-hydroxyvitamin D3 on the glucose and calcium metabolism in genetic obese mice. AB - In summary, it is demonstrated, for the first time, that there is a marked reduction of bone mass in ob/ob mice and this was restored by the treatment with 1 alpha-OH-D3. The effect of the sterol was accompanied by the improvement of hyperglycemia, hyperinsulinemia, and fat tissue responsibility to hormones. Thus, it is of interest to study obesity in terms of calcium homeostasis. PMID- 6267673 TI - Marked lethality of rats in combined exposure to carbon monoxide and diethyldithiocarbamate. AB - Simultaneous exposure of rats to carbon monoxide (COHb 60%) and diethyldithiocarbamate (i.p. 0.5 g/kg), a superoxide dismutase inhibitor, for 2.5 h resulted in a death of sixteen out of twenty-three rats. No rats treated with saline and exposed to CO died (0/26). There were no fatalities among the group of rats injected with the diethyldithiocarbamate solution and exposed to ambient air (0/16). PMID- 6267674 TI - Effect of ouabain on exogenous substrate oxidation by isolated cardiac myocytes. AB - Ouabain (10(-4) M) stimulated glucose oxidation and inhibited octanoate oxidation by isolated cardiac myocytes. Omission of potassium or calcium from the buffer abolished the ouabain stimulation of glucose oxidation. The inhibition of octanoate oxidation by ouabain persisted in the calcium deficient media. PMID- 6267676 TI - Inert gas elimination from lungs with stratified inhomogeneity: theory. AB - The effects of diffusion limitation in alveolar space (stratified inhomogeneity) on steady state inert gas elimination by the lung from blood are studied in theory. The lung models used for the calculations are characterized by a diffusion barrier in the alveolar space, which is quantified by a diffusive conductance (diffusing capacity), D'. In both homogeneous and inhomogeneous lung models (with log-normal distribution of VA, Q and D') increasing stratified inhomogeneity (decreasing D') is shown to diminish inert gas elimination. The effect, which depends on the solubility of the gases, is similar to the effect of alveolar dead space ventilation. PMID- 6267675 TI - Cardiac contractile and metabolic effects mediated via the myocardial H2-receptor adenylate cyclase system. Characterization of two new specific H2-receptor agonists, impromidine and dimaprit, in the guinea pig and human myocardium. AB - The present study chartacterizes myocardial effects of two new histaminergic H2 receptor specific compounds, impromidine, and dimaprit, on cardiac contractile and metabolic parameters of the guinea pig heart and human papillary muscle in comparison to the well-known effects of catecholamines. Impromidine and dimaprit produced a dose-dependent stimulation of the right and left ventricular contractile force in the isolated perfused biventricular catheterized guinea pig heart with maximal stimulation rates equal to those of isoproterenol. Hemodynamic equieffective doses of isoproterenol (2.8X10(-9) mol/l), histamine (1.1X10(-5) mol/l), impromidine (4.6X10(-7) mol/l, and dimaprit (8.5X10(-6) mol/l) induced nearly identical increases in tissue concentrations of c-AMP. All compounds dose dependently enhanced the activity of the myocardial adenylate cyclase with very similar KA-values in a particulate sarcolemmal membrane preparation of both guinea pig ventricles and human papillary muscles. No effect of either compound was seen on cardiac phosphodiesterase activity. Selective administration of the beta1-blocking agent metoprolol and the H2-receptor antagonist cimetidine clearly discriminates two independent receptors linked to the sarcolemmal adenylate cyclase system in the guinea pig and human myocardium. This is further supported by results obtained from beta-receptor-binding studies in which an interference of impromidine and dimaprit with the stereospecific binding of (-)[3H] dihydroalprenolol to cardiac beta-receptors could be definitely excluded. The possible therapeutic role of both H2-agonists on the non-ischemic, surviving myocardium, which is transiently refractory to beta-adrenergic stimulation by catecholamines after myocardial infarction, will be discussed. PMID- 6267677 TI - The direct effect of temperature on airway smooth muscle. AB - We tested the hypothesis that temperature may directly influence the resting membrane potential (Em), (Na+ + K+)-ATPase activity, and the contractile response to histamine of bovine and guinea pig airway smooth muscle. To determine the resting membrane potential of airway smooth muscle, glass microelectrodes filled with 3M KCl were used. As a measure of (Na+ + K+)-ATPase activity, potassium induced relaxation was used employing the method of Webb and Bohr (1978). The resting membrane potential and ATPase activity of airway smooth muscle was assessed 60 minutes after incubation in a normal oxygenated physiological salt solution (pH = 7.38 +/- 0.02) at each of the following temperatures: 21 degrees, 29 degrees, 37 degrees and 40 degrees C. The effect of ouabain (10(-5) M) and histamine (10(-3) M) on resting membrane potential of airway smooth muscle cells was also determined at each of these temperatures. It was found that: (1) resting membrane potential of airway smooth muscle cells from both bovine and guinea pigs, was directly proportional to the temperature; (2) the administration of ouabain reduced the dependency of resting membrane potential on the temperature of the experimental medium; (3) at lower temperatures (21 degrees C and 29 degrees C), histamine-induced a statistically significant (P less than 0.01) depolarization, and the contractile response of airway smooth muscle was also significantly (P less than 0.01) potentiated; (4) a decrease in the temperature (29 degrees C) significantly (P less than 0.001) decreased (Na+ + K+)-ATPase activity of airway smooth muscle as measured by potassium-induced relaxation. It is concluded that a change in temperature has a direct influence on airway smooth muscle cells, affecting resting membrane potential, (Na+ + K+)-ATPase activity of airway smooth muscle cells, and the contractile response of these cells to histamine. PMID- 6267678 TI - [Human red blood cells as specific growth hormone receptors (author's transl]. PMID- 6267679 TI - [Renal kallikrein and blood pressure (author's transl)]. PMID- 6267680 TI - [Two cases of paraneoplastic syndrome (author's transl)]. PMID- 6267681 TI - The release of inflammatory mediators from neutrophils. AB - Human polymorphonuclear leukocytes exposed to phagocytic stimuli undergo a series of cellular reactions designed to eliminate foreign invaders such as bacteria, viruses, or fungi. The responses of human granulocytes to the stimuli of phagocytosis are initiated at the cell surface and proceed in the following sequence: a. ligand binding to surface receptors; b. membrane hyperpolarization; c. O2- generation by a surface oxidase and 1O2 metabolism; d. generation of thromboxanes and prostaglandins; e. lysosomal enzyme secretion. These events, known as 'stimulus-secretion coupling', result in the secretion of toxic substances which, though intended to end up in the phagocytic vacuole, may escape to the extracellular space where they initiate inflammation. PMID- 6267682 TI - [A mixed malignant tumour of duodenum]. PMID- 6267683 TI - [Pretherapeutic metastases diagnosis in bronchial cancer with special reference to nuclear medicine procedures]. AB - In a retrospective study of 280 patients with histologically verified bronchogenic carcinoma, pretherapeutic diagnosis using scanning procedures yielded 13.6% skeletal metastases, 8.6% liver metastases and 3.6% brain metastases. The total 23.9% of hematogenous metastases proved to be dependent on the histological type of tumor: it was highest in small cell anaplastic carcinomas (38.8%) and large cell carcinomas (32.5%), and lowest in epidermoid carcinomas (13.3%). If the localization of metastases was also taken into account, the highest rates of metastases in the skeleton (17.5% and 22.5%) the liver (15%) and the brain (7.5%) were always found with small cell anaplastic and large cell carcinomas. Besides the histopathological type of tumor, the frequency of metastases depended also on the local stage of bronchial cancer. While scanning of the skeleton and the liver for clinical staging of bronchogenic carcinoma should always be regarded as an essential part of primary diagnosis (alternatively ultrasonography and computed tomography of liver) the necessity for brain scan and/or computed tomography depends on the neurological findings and the histomorphological type of tumor. PMID- 6267684 TI - [Cytomegalovirus pneumonia in primarily healthy adults]. AB - The case is reported of an 18-year-old woman hospitalized with severe dyspnea and high temperature. Chest X-ray showed pneumonia with interstitial and air-space consolidation patterns. Serologic tests revealed a cytomegalovirus infection (CMV). The blood findings showed anemia of infectious origin. Liver biopsy was consistent with CMV-hepatitis. CMV-pneumonia in an otherwise healthy patient is extremely rare; a review of the literature revealed only four other cases. PMID- 6267686 TI - [Some basic concepts and new trends in excitable membrane research]. PMID- 6267685 TI - [Diethylstilbestrol-induced liver cancer?]. AB - The case is reported of a 77-year-old man who died from hepatocellular carcinoma without accompanying cirrhosis, after being treated with a total of 668 g diethyl stilbestrol over a 12-year period for suspected carcinoma of the prostate. Possible relationships between this treatment and the hepatic cancer are discussed in the light of the relevant literature. PMID- 6267687 TI - Patterns of ACTH cells in the pituitary in Cushing's disease. PMID- 6267688 TI - Pertussis in pregnancy. AB - During the period July 1979 to April 1980 four pregnant women in one general practice were found to be suffering from pertussis. The diagnosis was based on clinical and serological evidence. The paper gives a clinical and bacteriological account for their progress and that of their babies. The possibility of pertussis occurring in expectant mothers at the present time is stressed. PMID- 6267689 TI - Cholangio carcinoma treated by liver split and resection. AB - A case of cholangiocarcinoma at the liver hilum presenting with jaundice is described. Pre-operative transhepatic cholangiography, hepatic arteriography and splenoportography led to liver split, with successful resection of tumour and triple hepatico-jejunostomy. Despite tumour recurrence eight months of palliation were achieved. Current methods of treating the condition are discussed. PMID- 6267690 TI - Combined modality treatment for glioblastoma multiforme. PMID- 6267691 TI - Morphine in cow and human milk: could dietary morphine constitute a ligand for specific morphine (mu) receptors? AB - Morphine has been found in cow and human milk at concentrations of 200 to 500 nanograms per liter. Multistep purification yields a material that has immunological, biological, pharmacological, and chemical properties identical to those of morphine. Similar morphine-like material, which has been tentatively identified in some common plant sources, may be a ubiquitous dietary constituent and a possible source for the material in milk. Since morphine (mu) receptors have a low affinity for enkephalins, and since morphine-like materials have been described in brain and intestine, it is possible that morphine in food may be the source of this material and a normal ligand specific for mu receptors. PMID- 6267692 TI - Milk of dairy cows frequently contains a leukemogenic virus. AB - Milk or viable milk cells collected from 24 dairy cattle naturally infected with bovine leukemia virus were inoculated into lambs, which were subsequently examined for the development of infection. With this bioassay, infectious virus was demonstrated in the milk of 17 of the cows. Bovine leukemia virus is leukemogenic in at least two mammalian species, is widespread in commercial dairy herds, and can infect a wide range of hosts in vivo and cells, including human cells, in vitro. PMID- 6267693 TI - Emergence of posttetanic potentiation as a distinct phase in the differentiation of an identified synapse in Aplysia. AB - The developmental time course of posttetanic potentiation was studied at an identified chemical synapse. In stage 11 juveniles (3 weeks after metamorphosis), the synaptic connections made by cholinergic neuron L10 onto postsynaptic neurons L2 to L6 were present but showed no posttetanic potentiation. In stage 13 adults (12 weeks after metamorphosis), the same tetanus resulted in an increase of 300 percent in the synaptic potential. A similar pattern was observed at two other identified synapses in the abdominal ganglion. Thus, the initial steps in synapse formation do not include the expression of this plastic capability. Rather, at least 10 weeks is required between the onset of synaptic function and the final expression of mature synaptic properties. PMID- 6267694 TI - Polymorphism in the 5'-flanking region of the human insulin gene and its possible relation to type 2 diabetes. AB - The arrangement of the human insulin gene in DNA from 87 individuals was analyzed by the Southern blot hybridization technique with a cloned genomic human insulin probe. Insertions of 1.5 to 3.4 kilobase pairs in the 5'-flanking region of the gene were found in DNA from 38 individuals. These insertions occurred within 1.3 kilobase pairs of the transcription initiation site. In contrast, no insertions were observed in the region 3' to the coding sequence. The prevalence of these insertions in type 2 diabetes was significantly greater than in the other groups (P less than .001). The limitation of this striking length polymorphism to a potential promoter region suggests that these insertions may play a role in insulin gene expression. PMID- 6267696 TI - Sodium pump in skeletal muscle: central nervous system-induced suppression by alpha-adrenoreceptors. PMID- 6267695 TI - Growth inhibition by adenosine 3',5-monophosphate derivatives does not require 3',5' phosphodiester linkage. AB - Analogs of adenosine 3',5'-monophosphate (cyclic AMP) inhibit the growth of cultured cell lines. The effects of 8-bromo- and N6-butyryl-substituted analogs of cyclic and noncyclic AMP on six cell lines were examined and were equally inhibitory. Variant cell lines with altered cyclic AMP-dependent protein kinase were more resistant to both cyclic and noncyclic nucleotides. We conclude that growth inhibition by analogs of cyclic AMP (i) does not require a 3',5' phosphodiester bond and (ii) may be mediated by a pathway involving endogenous cyclic AMP. PMID- 6267697 TI - Endogenous opiates and fasting. PMID- 6267698 TI - Gonadotropin-releasing hormone receptor binding and pituitary responsiveness in estradiol-primed monkeys. PMID- 6267699 TI - Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin. PMID- 6267700 TI - [A great surgeon at the beginning of this century]. PMID- 6267701 TI - [Syphilis. An up-to-date physio-biological view of the main topics. III -- The problem of immunity (author's transl)]. AB - The problem of immunity in Syphilis is a very complex problem which is tightly bound to healing. But for lack of being able to grow T. pallidum and as we are without any absolute criterion of bacteriological sterilization, the only method we have to be able to consider this study is to have recourse to experimentation upon animals. Two theories had been proposed to give an explanation about this phenomenon occurring during a late treated syphilis: on one side, for Kolle, Evers and Neisser, immunity in syphilis would be due to a premunition given by the only persistence in the organism of T.p. having still kept all their virulence. On the other hand, as far as Chesney and Kemp are concerned it would be a true immunity, obtained before the application of any therapeutic treatment, but which is not due to persistence of T.p. in tissues. However, recent works have proved, and this has been confirmed by several searchers, that a penicillin therapy, even at a high dose, given six months after the infection outset, is no longer able of destroying all T.p. Immunity in syphilis would then be due to a modification of tissular receptivity kept by the persistence of T.p. vegetating in the organism in a commensal state. As far as the nature of this immunity is concerned, all the present research would lead to prove that this refractory state would not be due to tumoral properties, but more likely to tissular properties and probably to cell mediated phenomena. Similar research carried out in man has created an opportunity to demonstrate these facts similar to those observed in experimentations upon animals. They particularly prove that a persistent serology over a long period is not due to a "cicatrice serologique" (Serological marker) but to the keeping of T.p. in a quiescent state. However, it is a more or less relative immunity which is concerned, depending upon a very large number of factors that are far from being elucidated. PMID- 6267703 TI - [Recurrent respiratory disease and IgA deficiency in infants and children (author's transl)]. AB - Among nearly 1 300 infants and children studied for chronic or recurrent respiratory diseases 36 of them had plasma and/or salivary IgA deficiency. They were 1 to 13 years of age with 20 between 3 to 6 years; 11 had total, lack or traces of salivary IgA, 9 had very low or nul plasma IgA titer and 6 had both. The deficiency was transitory in 10. Associated abnormalities with potential liability for the disease: allergy, gastroesophageal reflux, alpha-1-antitrypsin deficiency and other immunologic deficiency were encountered in 26. The often multifactorial pattern of respiratory diseases in pediatrics is emphasized. The pathogenic role of IgA deficiency is discussed. Even though its responsibility is demonstrated, its real magnitude and extent requires further studies. PMID- 6267702 TI - [Tetanus. An appraisal of 503 cases (author's transl)]. AB - Five hundred and three patients with tetanus were hospitalized in the intensive care unit of "Hopital Bretonneau" between January 1st, 1960 and December 31, 1979. An analysis of all these 503 cases is undertaken herein. The results of a similar study by the authors concerning 254 cases of tetanus were published in this journal in 1971 [16]. Frequent reference is made to the earlier study in order to evaluate any differences in prognosis which have occurred since that time. PMID- 6267704 TI - [Tiapride and algesic syndrome (author's transl)]. AB - The efficiency of the tiapride (3 x 100 mg) has been studied by the authors on a group of 20 patients presenting an algesic syndrome. The interpretation of the results depends on a scale from 0 to 3 varying with the intensity of pain. The antalgic effect usually starts 30 minutes later and lasts 8 hours or more for an injection of 100 mg. It appears from this study that the antalgic effect is not improved by increased dosage so that no advantage is found to increase the doses over 300 mg per 24 hours. The general and neurologic tolerance is excellent. PMID- 6267705 TI - [Prognostic anatomical features in the colon-rectum carcinoma (author's transl)]. AB - We have reviewed 415 cases of colon-rectum carcinoma in order to establish the most important prognostic anatomical features. Furthermore, we have examined the associated adenomatous polyps, and the possible relationships between anatomical and histological aspects and Dukes stage of carcinoma. We have searched for some useful parameters to decide whether 5 centimeters between neoplasia and resection line is the correct surgical treatment. PMID- 6267706 TI - [Interest of echotomography in the investigation of liquid renal collections (author's transl)]. PMID- 6267707 TI - [Xanthogranulomatous pyelonephritis. Report of eleven cases (author's transl)]. PMID- 6267708 TI - [Cure of chronic hepatitis B after treatment with basic aluminum hydroxide. One case report (author's transl)]. AB - The authors describe a case of cure of chronic hepatitis B. This therapy chronic hepatitis B was corticotherapy dependent and the cure appeared during a treatment with basic aluminum hydroxide. This drug is an adjuvant of immunity. Clinical and biological disturbances disappeared. An improvement of the histological liver disturbances during hepatitis cure had been noticed. Three years later no recurrence was observed. After a short review of published literature, the authors discuss the mode of action of basic aluminum hydroxide. PMID- 6267709 TI - [Renal disorders in cirrhotic patients: functional renal failure and metabolic acidosis (author's transl)]. AB - A study of renal tubular acidification in two cirrhotic patients with functional renal failure and partly compensated metabolic acidosis. Unlike renal distal tubular acidosis, but alike what is seen in organic renal failure, renal acidification was nearly normal and could not account per se for the development of metabolic acidosis. The multiple cause of the association in the cirrhotic of hyperchloremia and hypobicarbonatemia are reviewed (respiratory alkalosis, metabolic acidosis due to renal failure, distal tubular acidosis) and the diagnostic procedures outlined. PMID- 6267710 TI - [Iatrogenic menopause: a case report (author's transl)]. AB - A 25-year-old woman developed hot flushes due to the artificial menopause induced by cytotoxic chemotherapy (MOPP) during five years for Hodgkin's disease. Plasma FSH levels were found to be greatly elevated while those af 17 beta-oestradiol were markedly diminished. Veralipride was prescribed as one tablet (100 mg) daily for 20 days. Hot flushes disappeared completely, and no recurrence was observed during the 4-month follow-up period after discontinuation of treatment. Tolerance was excellent. This result is in agreement with those of studies reported in the published literature, relating to the treatment of hot flushes and psychofunctional disorders associated with both the natural and artificial menopause. PMID- 6267711 TI - [Primary iliac arterio-venous fistula from spontaneous rupture of an atheromatous aneurysm (author's transl)]. AB - The case of a patients, with a spontaneous arterio-venous fistula between the right common iliac vessels secondary to an atherosclerotic aneurysm of the artery, is presented. The authors, with the aid of the literature, recall the characteristic physical findings, the clues of the diagnosis and the modalities of the surgical treatment of such lesions. They insist on the importance of an early diagnosis as far as aneurysms are concerned, which allows to treat the lesions before complications arise. PMID- 6267712 TI - [A cause, sub-estimated in France, of the deadly necrotic enteritis: the enterotoxin of welchia (author's transl)]. AB - The symptoms and the lesions observed in the serious enteritis, often very severe, whose agent is W. perfringens A (and sometimes W. agni C) is an enterotoxin known only since the works of Hauschild (1971) and Duncan (1972). This enterotoxin is very different from the other toxinic factors of this anaerobic. This new toxin has been studied by foreign people and very little in France. It was isolated, purified and structured: it is a simple protein of PM +/ 34000, erythematous, inducing severe diarrhea, whose study was realized by the technic of ligatured ileal ansa of the rabbit. Its biosynthesis is related to the sporulation. In the experiment animal, it lyzes the intestinal villosities and denudes the membranes, what makes possible for the other toxins of A type to necrose the intestine. Its diagnostic evaluation is essential for a specific therapy. PMID- 6267713 TI - [Peroxidase and human thyroid hormone synthesis disorders (author's transl)]. AB - Thyroid peroxidase in involved in several steps of the biosynthesis of thyroid hormone utilizing H2O2: peroxidation of iodide to iodine, iodination of thyroglobulin (Tg) and coupling reaction leading to T4 and T3 formation. The peroxidase enzyme appears to be an heme protein containing a protoporphyrin IX, with binding sites for both iodide and tyrosine. Although the peroxidase is present in numerous cellular structure, iodination activity occurs primarily if not only at all, at the apical cell border. Lack of peroxidase activity or abnormal peroxidase has been described in isolated cases of congenital goiter with organification defect and a positive perchlorate test. However no change in enzymatic activity has been found in patients with Pendred's syndrome as compared to normal tissue. The deficiency of hormone synthesis observed in various benign diffuse thyroid disorders in certainly not due to a lack of peroxidase activity. In treated hyperthyroid patients, a high cellular activity is observed, especially at the apical cell border. In euthyroid patients with diffuse sporadic goiter, an increase of peroxidase activity is also observed. However, the cytochemical localization of the enzyme in goitrous thyroid gland shows that the peroxidase activity is mostly visualized around numerous lipoid structures; being concentrated in this particular site, the enzyme might preferentially oxidize lipids and consequently be less available for hormone synthesis. In euthyroid hot nodule, the peroxidase activity is normal. In cold nodule, a discrepancy between iodide oxidation and protein iodination has been found, suggesting that iodide peroxidation and iodination of tyrosine residues of Tg are two relatively independent processes although thyroid peroxidase catalyses both reactions. In contrast with the benign pathological conditions, the peroxidase activity is lower than normal in thyroid cancerous tissue. PMID- 6267714 TI - [The use of manganese-copper-oligosol in the treatment of chronic pharyngitis (author's transl)]. AB - Considering the difficulties involved in treating chronic pharyngitis and the frequent failure of therapies, the authors tried Manganese-Copper-Oligosol. The study involves 148 ambulatory patients who were given the drug twice daily in the morning and at midday, for a period varying from 1 to 3 months. The following informations were noted; the symptoms; the aspect of the mucous membrane; associated diseases, if any; predisposing factors; hygienic and alimentary habits. Global results: 46,5% good and very good results; 32,5% quite good results; 21% no result. The authors considered as good and very good the cases in which they noted both an objective aspect of the mucous membrane and a subjective improvement, the results were considered when the improvement was only objective. No intolerance or side effects were noted. PMID- 6267715 TI - Case report 152. Synovial sarcoma of the knee. PMID- 6267716 TI - [Intermediate structures, provisions for the sector]. PMID- 6267717 TI - Addison's disease as the sole clinical manifestation of recurrent bronchogenic carcinoma. PMID- 6267718 TI - Detection of recurrent breast cancer. AB - Most clinicians attempt to identify and treat recurrent breast cancer at the earliest sign of relapse. In an effort to better define the usefulness of commonly used clinical and laboratory tools in evaluating patients after mastectomy, we retrospectively analyzed 120 cases and reviewed the literature. One hundred fifteen sites of metastatic disease were identified in 55 patients, with bone, lung, liver, and skin most common. History and physical examination disclosed 66% of these metastatic events. Of 36 patients with probable bone involvement, 15 were identified by bone scan while asymptomatic. Of 31 patients with evidence of pulmonary metastases, 12 were entirely asymptomatic when identified with a screening chest roentgenogram. In contrast, 36 of 45 hepatic, cutaneous, lymphatic, central nervous system, and ocular metastases were suggested by purely clinical findings. We conclude that basic clinical skills (ie, history-taking and physical examination) are two most important means by which we identify patients with recurrent breast cancer. While chest roentgenogram and bone scan may uncover metastases in asymptomatic patients, liver function tests and radionuclide scans of brain and liver have very low yield in patients clinically free of organ involvement. PMID- 6267719 TI - Trophoblastic pulmonary embolism. AB - Trophoblastic embolism is subclinical in normal pregnancy, pronounced in eclampsia, and massive in hydatidiform mole. Self-limited acute respiratory distress arises in 3% to 10% of molar pregnancies at the time of uterine evacuation. Infrequently death occurs; the principal findings are trophoblastic emboli in the pulmonary arterioles, edema of the lungs, and dilatation of the right side of the heart. Hyperthyroidism may develop, and fibrin may line the alveolar walls. Pathogenetic mechanisms include heart failure, hyperthyroidism, dilutional anemia, and pulmonary arteriolar blockage. Infusions of fluid and whole blood tend to cause pulmonary overload, which may precipitate right-sided heart failure. Preferred therapy consists of diuresis and ventilatory support, especially with oxygen under positive end-expiratory pressure. PMID- 6267720 TI - Sensorineural hearing loss in young children: a systematic approach to evaluation. PMID- 6267721 TI - [Radiotherapy of Wilms' tumor]. PMID- 6267722 TI - The effect of clomiphene and conjugated oestrogens on cervical mucus. AB - The analysis of 157 menstrual in 50 patients on ovulation-inducing regimens showed that in restoring ovulation clomiphene citrate inhibited cervical mucus production and caused hypersecretion of oestradiol. The inhibitory effect was inversely proportional to serum oestradiol levels, and the addition of conjugated oestrogens did not rectify the inhibitory effect, increase plasma oestradiol levels or increase cycle length. Doubling the clomiphene dosage made no significant difference to any of the parameters examined. The mechanism of this inhibitory effect is still obscure. PMID- 6267723 TI - [Systemic causes for malocclusion]. PMID- 6267724 TI - Hepatic transplantation. PMID- 6267726 TI - [Physiological and pathological principles of pain and some features of the interpretation of vertebral backaches]. PMID- 6267725 TI - Primary liver cancer and its relationship to chronic infection with the hepatitis B virus. PMID- 6267728 TI - Effects of 12-O-tetradecanoyl phorbol 13-acetate on platelet aggregation. PMID- 6267727 TI - Raised enzyme markers of chronic inflammation in asymptomatic farmers' lung. AB - Subclinical inflammatory activity may be one of the factors which influences the variable natural history of farmers' lung. Serum lysozyme (LYS) and angiotensin converting enzyme (ACE) have been measured in 52 farmers with a previous history of farmers' lung and in 51 healthy control farmers. The group with farmers' lung assessed during the winter, although having had no recent acute symptoms, had significantly higher levels of LYS and ACE compared to both healthy control farmers seen in winter and farmers' lung subjects seen in summer. There was a mild but significant negative correlation between LYS and farm size in the farmers' lung subjects assessed in winter. The results suggest that active inflammation may be present in subjects with farmers' lung in the absence of acute symptoms during the season when dust exposure occurs as the result of feeding cattle. PMID- 6267729 TI - Incidence of EDS'76 virus infection in fowl in 1980 in the Netherlands in comparison with the incidence in 1976-1978. AB - Serological examinations demonstrated that Egg Drop Syndrome 1976 (EDS'76) virus infection was of no significance in the Dutch poultry industry in 1980, in contrast to the situation in 1976-1978 when this infection was of widespread occurrence. The conclusion was reached that the sharp decrease in the incidence of EDS'76 virus infection was due to large scale vaccination in 1978 and 1979. The results of this study show that there is no further need for general EDS'76 vaccinations. However, continuous serological monitoring is necessary to detect flocks for which vaccination is indicated. PMID- 6267730 TI - [Diagnosis of lipid malabsorption]. PMID- 6267731 TI - [Brain atrophy as an artifact in ACTH administration]. AB - An 8-month-old infant was treated for infantile spasms with long acting corticotrophin 25 IU daily for 32 days. CT, done 2 weeks after the treatment was discontinued, suggested diffuse brain atrophy. Repeat CT one year later was only borderline abnormal. No shift in the skull circumference curve was noted. Comparison to the literature led to the conclusion that the reversible changes in CT were caused by ACTH. The nature of this phenomenon is discussed as well as the implications for CT-diagnosis. The question arises whether ACTH or corticosteroids might cause irreversible brain damage. PMID- 6267732 TI - Cytological and immunological examination of cerebrospinal fluid in 9 patients with Ramsay Hunt's syndrome. AB - The purpose of the present study was to carry out the immunological and cytological examination of cerebrospinal fluid in 9 patients with Ramsay Hunt's syndrome. The results obtained were as follows: Among the serum immunoglobulins, IgG in 1 and IgM in 5 of 9 cases increased. The Varicella Zoster antibody titer was significantly elevated in sera of all 9 cases and in CSF of all 7 examined cases. There ws positive fluorescence to Varicella Zoster virus in 2 (Cases 8 and 9) of 4 cases in which CSF smears were examined. The cells showing fluorescence were 10.5% in the former and 1.5% in the latter. Pleocytosis was found in all cases and CSF cell counts ranged from 52 to 2,000/3 mm3 in the early stage. In 3 cases immunoglobulin containing cells (IgG and IgM) were seen about 2-20% within 2 weeks of onset. IgG contents in all and IgG% in 8 of 9 cases, IgA concentration in 7 and IgA% in 7 of 9 cases were increased. These results support the view that the Varicella Zoster virus spreads to the meninges and CSF from ganglions in patients with Ramsay Hunt's syndromes. PMID- 6267733 TI - Biochemical changes in the rat cerebellum following cypermethrin administration. PMID- 6267734 TI - The role of cyanide liberation in the acute toxicity of aliphatic nitriles. PMID- 6267735 TI - Induction of benzo[a]pyrene metabolism by 2,3,7,8-tetrachlorodibenzo-p-dioxin in primary cultures of adult rat hepatocytes. PMID- 6267736 TI - Effects of 2,3,7,8-tetrachlorodibenzo-dioxin (TCDD) on early life stages of rainbow trout (Salmo gairdneri, Richardson). AB - Rainbow trout eggs, yolk sac fry and juveniles were exposed to 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) in different concentrations for 96 h. Exposure of eggs to the lowest concentration, used in this study, 0.1 ppt (10-13 glg), resulted in a significant growth retardation for 72 days. At higher concentrations significant numbers of the forthcoming fry developed generalized edemas and died. Histologically, degeneration and necrosis of liver parenchymal cells were observed. Remaining fry showed teratologic changes as foreshortened maxillas and opercular defects. Administration of TCDD to yolk sac fry had similar effects. Juvenile rainbow trout, exposed to 10 and 100 ppt TCCD for 96 h, showed growth retardation and developed slight edematous changes. At 100 ppt all fry had died within 27 days. Histologically, vacuolization of the liver parenchymal cells and intracellular inclusion bodies in liver, pancreas and stomach were observed. PMID- 6267738 TI - A neutral DNase in venom sac extract of the Oriental hornet Vespa orientalis: characterization, specificity and mode of action. PMID- 6267737 TI - Effect of citreoviridin, a toxin from Penicillium citreoviride NRRL 2579, on glycogen metabolism of rat brain. PMID- 6267739 TI - Biochemical characterization of a toxin from Indian cobra (Naja naja naja) venom. PMID- 6267740 TI - [Radiation therapy in bronchial carcinoma (author's transl)]. PMID- 6267741 TI - Enzymatic changes in rat thymus after intraperitoneal injections of adrenocorticotrophic hormone and corticosterone. AB - Intraperitoneal injection in adult male rats with adrenocorticotrophic hormone (ACTH) (0.6 mU daily for 3 days) brought about a marked decrease in the activities of four thymic enzymes studied: glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, isocitric dehydrogenase, malic dehydrogenase. A prominent rise in the levels of these enzymes occurred when ACTH was replaced by corticosterone (1 mg injected daily for 3 days). In adrenalectomized rats, the results were similar to those observed in intact animals. The significance of an increase in transaminase activities after corticosterone treatment, relating to an increase in citric cycle enzymes is discussed. On the other hand, it was suggested that ACTH exerts an extra adrenal effect on the thymus. PMID- 6267743 TI - Clinical and epidemiological features of adenovirus keratoconjunctivitis. AB - The pattern of adenovirus infection of the eye in the Bristol area has been considered over a period of 9 years. During this time three outbreaks of keratoconjunctivitis, caused in turn by serotypes 8, 10/19, and 4, were observed. When adenoviruses are subdivided into three groups, based on their haemagglutination properties, it is evident that those serotypes responsible for epidemic keratoconjunctivitis belong to Group II. Ocular infection by serotypes in Groups I and III usually results in a follicular conjunctivitis, with or without upper respiratory tract infection, and with markedly less corneal involvement. PMID- 6267742 TI - Medical correlates and diabetic retinopathy screening. AB - A systematic ophthalmological, medical, and biochemical screening of a rural population of diabetics in Western Australia is being carried out. A team of ophthalmologists, physicians, and paramedical personnel establish regional screening centres on a voluntary basis at weekends. Every attempt is made to locate and examine all known diabetics. All patients are given a thorough ophthalmic examination including standard multiple field colour fundus photography. Thorough physical examination includes assessment of cardiovascular and neurological status. Biochemical parameters include random blood sugar, urine analysis, serum creatinine, glycosylated haemoglobin, cholesterol, and high density lipoprotein. A detailed questionnaire and interview is carried out to assess the historical degree of control and the patient's knowledge of the control and management of diabetes. The sample now comprises an unselected population of 400 diabetics living in rural areas and allows comparison of areas which have scarce medical services with centres that are well supplied with medical practitioners. Incidence of retinopathy varies from 25 to 36 per cent of the diabetic population. Positive correlations of retinopathy have been found with duration, age, hypertension, level of control assessed biochemically at the time of examination, presence of ischaemic heart disease, peripheral neuropathy, and renal disease. Smoking also correlates positively. The data provide a baseline by which attempts to alter diabetic knowledge, management, and control may be measured in follow-up studies. PMID- 6267744 TI - Virulence of Entamoeba histolytica in rat and its comparison with the serological responses of the amoebic patients. AB - The virulence of 70 isolates of Entamoeba histolytica was studied in the Wistar strain of albino rat by intracaecal inoculation of amoebae. The results were evaluated by the Neal scoring system, histopathological grading of ulcers and virulence indices. It was found that isolates from acute amoebic cases could infect and produce ulcers in significantly more animals than could the isolates from asymptomatic cyst passers. The virulence indices of isolates from acute cases were also significantly higher as compared to those from asymptomatic cyst passers. However, there was no significant difference between virulence indices of isolates from acute cases and non-dysenteric amoebic colitis. This study also showed that Neal scores failed to correlate with the type of pathology produced by the amoebae in the caecum. It is felt that virulence indices which depend upon the histopathological lesions should also be taken into consideration. The serological response of the patients tended to correlate with the virulence indices of isolates but only minimally. The results thus contradict a common belief amongst clinicians that higher levels of anti-amoebic antibodies reflect severe disease, as compared to low levels of antiamoebic antibodies. PMID- 6267745 TI - Effects of splenectomy and Sendai virus infection on rejection of male skin isografts by pathogen-free C57BL/6 female mice. AB - Using C57BL/6 female mice raised under pathogen-free conditions, it was confirmed that splenectomy prior to grafting promotes brisk rejection of male skin isografts. These mice were than used to examine the influence infection with Sendai virus might have on this phenomenon. It was found that Sendai virus infection of skin graft donors renders the grafts prepared therefrom highly susceptible to the rejection process. Sendai virus infection of female recipients of male isografts had a trivial effect on the ability of these females to reject their test grafts. However, if Sendai-infected females had their spleens removed 7 days before grafting, they exhibited a markedly accelerated rejection process. These studies indicate that viral epizootics within a murine colony, especially if unsuspected, may confuse the accurate interpretation of experimental skin grafting data. PMID- 6267746 TI - Graft-versus-host reaction in the lung. PMID- 6267747 TI - Persistent, recurrent, and late cytomegalovirus infection. PMID- 6267748 TI - Cytomegalovirus vaccine in renal allograft recipients. PMID- 6267749 TI - Better allograft survival in erythrocyte type-O recipients correlates with resistance to cytomegalovirus infections. PMID- 6267750 TI - Bone marrow ablation and marrow transplantation in acute leukemia: influence of clinical pretransplant condition. PMID- 6267752 TI - Suppression of renal allograft rejection by low density thymocytes. PMID- 6267751 TI - Autologous bone marrow transplantation in neoplasia. PMID- 6267753 TI - The Epstein-Barr virus (EBV) in the pathogenesis of posttransplant lymphoma. PMID- 6267754 TI - Susceptibility to murine viral diabetes: host versus intrinsic pancreatic factors. PMID- 6267755 TI - Biliary reconstruction methods for liver transplantation. PMID- 6267757 TI - Crystals in a gastric schwannoma. AB - A gastric schwannoma containing large numbers of intracytoplasmic crystals is described. The latter are compared with intracytoplasmic crystals found in the cells of other tumors and their nonneoplastic cell counterparts. The extreme morphologic and histochemical heterogeneity of the different types of crystals is emphasized. PMID- 6267756 TI - Dual differentiation in small cell carcinoma (oat cell carcinoma) of the lung. AB - Two cases of small cell "undifferentiated" carcinoma (oat cell carcinoma) of the lung with dual neurosecretory and squamous differentiation are reported. One was treated with various regimens of chemotherapy and radiotherapy; the other was untreated at the time of biopsy. By electron microscopy, the same tumor cells showed membrane-bound, dense-core, neurosecretory-type granules and bundles of tonofibrils denoting squamous differentiation. This dual differentiation underlies the difficulty of ascribing an exclusively neural histogenesis to small cell carcinomas with neurosecretory-type granules. It is possible that entoderm associated neuroectodermal tumors develop features of autochthonous entodermal tumors as a result of microenvironmental influences. An alternative hypothesis would be that small cell tumors are derived from basal reserve bronchoepithelial cells with pluripotentialities. PMID- 6267758 TI - Eosinophilic bodies in the epidermis. PMID- 6267759 TI - Nasal blastoma. PMID- 6267760 TI - [Hypophysectomy in the combined treatment of prostate cancer]. PMID- 6267761 TI - The ultrastructure of dog epididymis. AB - The ultrastructure of the epididymal duct and ductuli efferentes in the dog has been studied by electron microscopy. The epididymidis can be separated into the classical divisions of caput, corpus and cauda epididymidis on the basis of general morphology and ultrastructure. The ductuli efferentes have a low epithelium with pronounced cilia at the apices of cells and appear to provide primarily a transport role for spermatozoa. In the epididymis proper the caput region is characterized by an extremely large Golgi apparatus with large numbers of lysosomes and nuclear inclusions. Secretory activity appears to be most common in the corpus region. Absorption and secretion are most active in the first two segments while in the cauda epididymidis the long-term storage of spermatozoa in the lumen is associated with many dense crystalline bodies formed in the epithelial cells within the Golgi apparatus and possibly deriving from absorbed macromolecular material from the lumen. The theory of whole sperm cell resorption by the epididymal duct is not supported by this study. PMID- 6267762 TI - [Immunization of cattle against Aujeszky's disease with inactivated adjuvant vaccine]. AB - The experiments with sheep and young cattle were carried out to test the immunizing efficacy of inactivated adjuvant vaccine against Aujeszky's disease. The vaccine application at doses of 1 ml and 2 ml to lambs at the age of eight to ten months caused the neutralizing antibody production with a significant rise of titres after revaccination. A survival of infection induced with a dose of 10(5.5) TKID50 of virulent virus was recorded in 62.5% of once vaccinated animals and in 87.5% of twice vaccinated animals. When applying different doses of vaccines (from 1 to 10 ml) to young cattle, the antibody reaction level was directly dependent on the inoculum quantity. The double inoculation of animals with vaccines of 2 ml and 5 ml caused the neutralizing antibody production at titres of 1:35, or 1:46. The animals, immunized with the live or inactivated IBR vaccine possessing high antibody titres against IBR-virus, reacted upon the vaccination with inactivated Aujeszky's vaccine anamnestically, by early production of antibodies in high titres. Metaphylactic vaccination (2 ml of vaccine) of cattle in herds with an acute course days, however earlier during five days from the revaccination when it was carried out in seven days following the first vaccination. PMID- 6267763 TI - [Comparison of 2 inactivated vaccines against Aujeszky's disease in pigs]. AB - Equal efficiency was proved by comparing two inactivated vaccines against Aujeszky's disease (AD) virus manufactured in Czechoslovakia. Fifteen porkers at the age of four weeks were included in the experiment, not possessing any specific antibodies to AD virus. Each vaccine was inoculated intramuscularly to five porkers (2 ml) in the interval of three weeks. The third group of five porkers was control. The samples of blood serum were subjected to the serum neutralizing test and radioimmunoassay (RIA) 21 and 35 days after vaccination. Three weeks after vaccination, antibody titers were demonstrated in nine from ten vaccinated porkers by RIA, in one pig by SNT. All 15 porkers were challenged with live virulent strain of the virus on the 35th day after the start of the experiment. The ten vaccinated porkers survived the infection after a short feverish disorder. Out of the five unvaccinated controls four pigs died; the patho-anatomic findings demonstrated necrotic tonsillitis and lobar bronchopneumonia. The finding in the fifth control porker was identical; the porker was killed 15 days after infection. PMID- 6267764 TI - The diagnosis of viral disease in equine practice. PMID- 6267765 TI - IBR virus excretion after vaccination. PMID- 6267766 TI - In vitro culture of feline infectious peritonitis virus. PMID- 6267767 TI - [Combined prevention of viral infections in cattle]. AB - On the basis of clinical observations and serological investigations a mixed type of virus infection of MD-VD parainfluenza-3 and adenovirus I was established. A complex prophylaxy against the virus infections proved in 2,800 heads of cattle was carried out, also on 1,400 heads of growing animals at the age between 6 and 18 months, as well as on 2,777 calves at the age of 6 months. The results of the immunoprophylactic actions showed the leading role of MD-VD in a virus infection. Owing to the steps taken the respiratory syndrome in the calves and in the cows was suspended. The falling away of calves was reduced from 15.4% to 3.2%, and the average daily growth was increased from 220 to 470 grams. PMID- 6267768 TI - [Serological studies of the dissemination of neutralizing antibodies against the mucosal disease-viral diarrhea virus in cattle]. AB - During a serological study of 56 samples from cows, taken from prosperous farms, were proved in 37.5% neutralizing antibodies against the MD-VD, whereas the study of 89 samples from cows, taken from failing farms, the neutralizing antibodies against the same virus were 50.3%. Out of the 145 serum samples from calves, originating from prosperous farms 30.5% proved positive for neutralizing antibodies against the MD virus. Out of the 151 samples from calves, originating from failing farms, 65.7% proved positive. The data show the high degree of dissemination of the virus of that disease both on prosperous and on failing farms. PMID- 6267769 TI - Intracytoplasmic granules of the inner medulla and papilla of the potassium depleted human kidney. AB - Morphological changes were studied in the kidney of a potassium depleted 21-year old Japanese male with Bartter's syndrome. Characteristic features were PAS positive intracytoplasmic granules in the inner medulla and the papilla. The intracytoplasmic granules were conspicuous towards the papillary tip and ultrastructurally composed of small vesicles, vacuoles, amorphous dense materials, lamellar contents and myelin like figures, and bounded by a single limiting membrane. The granules in this human kidney were, with regard to their distribution and ultrastructural findings, similar to those in the kidney of experimentally potassium depleted rats. The results indicate that the intracytoplasmic granules in the renal inner medulla and the papilla are the characteristic feature of the potassium depleted human kidney and a counterpart to those in the potassium depleted rat. PMID- 6267770 TI - Restriction endonuclease mapping of the DNA of Rous-associated virus O reveals extensive homology in structure and sequence with avian sarcoma virus DNA. PMID- 6267771 TI - Organization of the endogenous proviruses of chickens: implications for origin and expression. PMID- 6267772 TI - Integration of avian sarcoma virus DNA in chicken cells. PMID- 6267773 TI - Identification of a novel human papilloma virus in cutaneous warts of meathandlers. PMID- 6267774 TI - Endogenous proviruses of random-bred chickens and ring-necked pheasants: analysis with restriction endonucleases. PMID- 6267775 TI - Syncytium formation induced by baboon endogenous virus in several transformed human cell lines. PMID- 6267776 TI - The structure and protein kinase activity of proteins encoded by nonconditional mutants and back mutants in the sec gene of avian sarcoma virus. PMID- 6267777 TI - Generation and amplification of temperature-sensitive mutants during serial undiluted passages of vesicular stomatitis virus. PMID- 6267778 TI - Characterization of a 105,000 molecular weight gag-related phosphoprotein from cells transformed by the defective avian sarcoma virus PRCII. PMID- 6267780 TI - Mammary tumors from GR mice contain more than one population of mouse mammary tumor virus-infected cells. PMID- 6267779 TI - In vitro replication and assembly of vesicular stomatitis virus nucleocapsids. PMID- 6267781 TI - Ribosomal binding sites on poliovirus RNA. PMID- 6267782 TI - Cloning of the marmoset herpesvirus thymidine kinase gene and analyses of the boundaries of the coding region. PMID- 6267783 TI - Characterization of HEL-12 virus proteins. PMID- 6267784 TI - Early DNA-binding polypeptides of Epstein-Barr virus. PMID- 6267785 TI - Growth of phages lambda and phiX174 under Plban protein control in the absence of host dnaB function. PMID- 6267786 TI - Molecular heterogeneity and lesion site specificity of cutaneous bovine papillomaviruses. PMID- 6267787 TI - Construction of a double-jointed herpes simplex viral DNA molecule: inverted repeats are required for segment inversion, and direct repeats promote deletions. PMID- 6267788 TI - Secretion of a virus-regulated factor by clonal variants of reticuloendotheliosis virus-transformed hematopoietic cells. PMID- 6267789 TI - A physical map of the linear unintegrated DNA of Visna virus. PMID- 6267790 TI - Comparative sequence analysis of the 5'terminal noncoding regions of poliovirus vaccine strain Sabin 1, Sabin 2, and Sabin 3 genomes. PMID- 6267792 TI - Inhibition of herpes simplex virus transformed and nontransformed cells by acycloguanosine: mechanisms of uptake and toxicity. PMID- 6267791 TI - Monoclonal antibodies to lymphocytic choriomeningitis and pichinde viruses: generation, characterization, and cross-reactivity with other arenaviruses. PMID- 6267793 TI - Biochemical transformation of LM(TK-) cells by hybrid plasmids containing the coding region of the herpes simplex virus type 1 thymidine kinase gene. PMID- 6267794 TI - Origin of mink cytopathic focus-forming (MCF) viruses:comparison with ecotropic and xenotropic murine leukemia virus genomes. PMID- 6267795 TI - Role of protease in mouse hepatitis virus-induced cell fusion. Studies with a cold-sensitive mutant isolated from a persistent infection. PMID- 6267796 TI - Protein kinase activity associated with Epstein-Barr virus-determined nuclear antigen. PMID- 6267797 TI - Inhibition of adenovirus-transformed cell oncogenicity by adeno-associated virus. PMID- 6267798 TI - Reovirus enzymes that modify messenger RNA are inhibition by perturbation of the lambda proteins. PMID- 6267799 TI - Visna virus DNA: discovery of a novel gapped structure. PMID- 6267801 TI - Modification of membrane permeability induced by animal viruses early in infection. PMID- 6267800 TI - Interaction of psoralen derivatives with the RNA genome of Rous sarcoma virus. PMID- 6267802 TI - Rapid emergence of mink cell focus-forming (MCF) virus in various mice infected with NB-tropic friend virus. PMID- 6267803 TI - A paranuclear extract contains a unique set of viral transcripts late in SV40 infection. PMID- 6267804 TI - Characterization of transformation- and replication-specific sequences of reticuloendotheliosis virus. PMID- 6267805 TI - Characterization of an influenza A virus from seals. PMID- 6267806 TI - Two cellular proteins that immunoprecipitate with the transforming protein of Rous sarcoma virus. PMID- 6267807 TI - Myeloid and erythroid neoplastic responses to avian defective leukemia viruses in chickens and in quail. PMID- 6267808 TI - Physical map of the bacteriophage P22 genome. PMID- 6267809 TI - Immunoselection of simian virus 40 large T antigen messenger rnas from transformed cells. PMID- 6267810 TI - Cyclic GMP and visual cell degeneration in the inherited disorder of rd mice: a progress report. PMID- 6267811 TI - Studies on retinal capillary cells in tissue culture. PMID- 6267813 TI - Properties of a Na-K ATPase inhibitor in cultured lens epithelial cells. PMID- 6267812 TI - Differentiation of rat lens epithelial cells in tissue culture--IV. Some characteristics of the process, including possible in vitro models for pathogenic processes in cataractogenesis. PMID- 6267814 TI - [Lung cancer after a foreign body (polyvinyl chloride) remaining 2 years in the bronchus]. PMID- 6267815 TI - [New method of thymus transplantation]. AB - A surgical procedure for correction of T-system immunity deficiency in primary immunodeficient states and malignant neoplasms in children is described. To ensure a high physiological activity of the transplant, to prevent anti-recipient reaction and to maintain laminar blood flow in the transplant, thymus glands were obtained from fetuses and separated from breast bone. Blood channel reconstruction was performed before the gland transplant was washed and connected to the patient's blood flow. Thymus transplantation was carried out in 25 cases and neither acute rejection nor anti-recipient reaction were observed. Immune response indices returned to normal within 6-7 months. PMID- 6267816 TI - [Transfection method of searching for herpes virus genetic information in the tumor tissue of cervical cancer patients]. PMID- 6267817 TI - Screening blood donors for high titre antibody to herpes varicella-zoster. AB - As a method of increasing supplies of varicella-zoster immunoglobulin, semi automated screening of blood donors for high titre complement-fixing antibody was initiated. This was compared with the previously used method of donor selection based on a history of varicella or zoster in the past 6 months. About one-third of the "history" donors had titres of greater than or equal to 1 in 64 and generally these levels declined rapidly. In contrast, although only 1.1% of donors in random screening had antibody titres greater than or equal to 1 in 64, these levels usually remained high during repeated donation, enabling the production of pools entirely composed of high titre plasma packs. PMID- 6267818 TI - [Cytological characteristics of bronchogenic carcinoma]. PMID- 6267819 TI - [Features of immunogenesis in simians infected with attenuated strains of tick borne encephalitis and Langat virus]. AB - Certain parameters of humoral and cellular immunity induced by attenuated tick borne encephalitis (TBE) and Langat virus strains were studied in monkeys. The immunogenic activity of the strains inoculated subcutaneously and intracerebrally was manifested by two processes: synthesis of specific antibody and cellular immune response. The highest titers of humoral immunity in N, HI, and CF tests were observed to homologous viruses. The immune response to both homologous and heterologous viruses could be optimized by increasing the number of antigenic stimulations. The sequence of antibody synthesis of the macro- and microglobulin series was similar in monkeys infected with virulent and attenuated strains. Cellular immunity reactions were detected and changes in the quantity and functional activity of T- and B-lymphocytes were determined. Most marked immunological changes were observed with the virulent TBE virus strain as compared with naturally and experimentally attenuated Langat virus strains. PMID- 6267820 TI - [Enteroviruses in the water of surface reservoirs of the GDR and USSR]. AB - Virological examinations of water from rivers, channels, lakes, and water reservoirs were carried out in two countries, the GDR and the USSR, in 1973-1974. The occurrence of enteroviruses in all the water bodies was demonstrated. The infection rate of water with viral and bacterial flora and water pollution with organic suspension was found to be dependent upon sewage drainage. The canals (GDR) and rivers (USSR) into which sewage of large densely populated towns were discharged were found to be most highly infected (67% and 36% of virus-containing samples, respectively). The least infected were lakes and water reservoirs receiving no or small quantities of sewage. The difference between the values indicating virus infection and pollution with organic substances in water bodies receiving and not receiving sewage was statistically significant. PMID- 6267821 TI - [New antigens induced by herpes simplex virus in human tumors]. AB - Tissues of malignant tumors of the genitalia (cervix, uterus body, ovary) contain a specific antigen associated with herpes simplex virus type 2 (HSV-2) identical with the antigen of the infected cells. The virus-induced antigen was detected in tissues of cervical carcinoma in 35% of cases, in 15% of tumors of the corpus uteri and in 13% of ovary tumors. HSV-2 was isolated from pathologically altered cervical carcinoma cells in 2 out of 56 cases examined. These facts indicate the presence of HSV-2 genetic information in cells of some tumors. No virus-induced antigen was found in any of the 7 specimens of normal nontumorous tissue examined. PMID- 6267822 TI - [Development and utilization of an immunoenzyme technic to diagnose arenavirus infections]. AB - The possibility of using ELISA for the detection of arenavirus antigens in different organs of infected newborn white mice as well as in the culture fluids of arenavirus-infected cell cultures was demonstrated. The sensitivity of ELISA in antigen detection 100-200 times exceeds that of the CFT, and the time of antigen detection after inoculation of animals or cell cultures is much shorter. The use of ELISA block for the detection and titration of virus-specific antibody also demonstrated high sensitivity of this method as compared with the CFT. PMID- 6267823 TI - [New endogenous proviruses in the genome of brown Leghorn chickens]. AB - Genetic differences and differences in localization of endogenous proviruses in chicken genomes were found in studies on endogenous provirus sequences in DNA of white and brown Leghorn chickens. In brown Leghorn DNA, proviruses both similar with Raus-associated virus (endogenous virus of white Leghorns) and differing from it in the pattern of hydrolysis by EcoRI restricting endonuclease were found, the latter occurring more frequently. Different sets of variously localized proviruses were found in DNA of individual chickens; none of the proviruses was found in DNA of all brown Leghorns examined. No single provirus common for chickens of the two species was found. The genetic diversity of endogenous proviruses observed in brown Leghorns indicates the possibility of coexistence in the chicken DNA of message on several significantly different endogenous viruses. PMID- 6267825 TI - An American physician in rural West Africa. PMID- 6267824 TI - [Cytochemical study of granulocyte enzymes in germ-free animals with adenovirus infections]. AB - The activity of some dehydrogenases and hydrolases was studied by cytochemical methods in the peripheral blood neutrophils of germ-free guinea pigs infected with adenoviruses. The gnotobiotic animals were obtained by hysterotomy in an operation isolation room after which they were transferred into manipulation isolation room and infected with human adenovirus type 1. A depression of enzymes of alpha-glycerophosphate shunt and NADP-H2-diaphorase in neutrophils two days after infection and activation of lactate dehydrogenase and acid phosphatase at 4 days were demonstrated. The pattern of changes in the enzymatic status of intact and infected gnotobiotic animals allowed a diagnosis of adenovirus infection in most cases. PMID- 6267826 TI - [Hypophosphatemic rickets in 3 patients (Albright-Buttler-Bloomberg syndrome)]. PMID- 6267827 TI - [Spontaneous pneumothorax in primary bronchial neoplasm]. PMID- 6267828 TI - [Alveolar carcinoma]. PMID- 6267829 TI - [Report on the results achieved over the past 10 years in the neuro-orthopaedic out-patient department (author's transl)]. AB - A short abstract of the pathophysiology of pain and its conduction is followed by a discussion of the importance of neurological-orthopaedic cooperation for the diagnosis and the treatment of pain syndromes arising from the locomotor apparatus. The examination of the spine from the functional, i.e. segmental point of view is pointed out. The main reflex answer of the spine to irritation is the restriction of movement or hypermobility. Therefore, neuro-orthopaedic reflex treatment consists of so-called "test treatment" by means of manipulation to overcome the restriction of movement or by local curative anaesthesia, or by a combination of both methods. The results over the past decade of treatment in 1008 patients suffering from various pain syndromes are presented and differentiated. PMID- 6267830 TI - [Fungal infections -- always dangerous for immunosuppressed patients (author's transl)]. AB - Four renal transplant recipients, treated with the immunosuppressive combination of azathioprine-prednisolone, developed organ or systemic mycoses caused by Candida albicans and, in one case, additionally by Trichophyton rubrum. Ketoconazole, a new wide-spectrum antimycotic drug, was successfully used in the treatment of the fungal infections in these patients. The oral route of administration, good tolerance and excellent results are good recommendations for this drug. PMID- 6267831 TI - Problems associated with I-125 oxytocin binding to membrane receptors. PMID- 6267832 TI - Respiratory ubiquinone-9 from Hyphomicrobium spec. Strain ZV 580. AB - Ubiquinone-9, an ubiquinone with a side-chain containing 9 prenyl residues, was purified from Hyphomicrobium spec. strain ZV 580, and identified by thin-layer chromatography, UV spectroscopy, and mass spectrometry. The participation of the quinone in the reactions of the respiratory chain was established by observing its increasing reduction in a membrane fraction upon the addition of NADH, the exhaustion of oxygen, and in the presence of NADH plus cyanide. The degrees of reduction in these states matched those of the cytochromes b and c. PMID- 6267834 TI - Dihydroxyacetone kinase of methanol-assimilating yeasts. II. Partial purification and some properties of dihydroxyacetone kinase from Candida methylica. AB - Dihydroxyacetone kinase (DHAK) from the cell-free extract of methanol-grown Candida methylica was partially purified about 100-fold by a procedure employing streptomycin sulfate fractionation, ammonium sulfate fractionation, negative absorption on Cibacron blue F3G-A sephadex G 200 and DEAE-cellulose column chromatography. The enzyme was stable in 50 mM Tris-HCl buffer pH 7.5 containing 60% glycerol at -18 degrees C. The pH optimum for the activity of DHAK from C. methylica was 7.5. The purified enzyme phosphorylated dihydroxyacetone four times faster than D,L-glyceraldehyde. The apparent MICHAELIS-MENTEN constants for dihydroxyacetone and D,L-glyceraldehyde were 0.011 mM and 0.024 mM. Other C3 compounds including glycerol were not phosphorylated. ITP and UTP were used as phosphate donors with a reaction rate of 11% and 3.1%, respectively, in relation to ATP, whereas the reaction rates of DHAK from C. methylica with CTP or GTP were much lower than 1%. The reaction of DHAK depends upon the presence of divalent cations in the assay. The highest activity was found with Mg2+ ions. The reaction rates with Co2+ or Ca2+ ions were only 57.3% and 30.3%, respectively, in relation to the assay with magnesium ions. Manganese chloride in the assay led to a complete loss of activity. PMID- 6267833 TI - Inhibitor studies of phage T4 wild-type and mutant DNA polymerases. V. A. summary of kinetic and inhibitor data. AB - The DNA polymerases of phage T4 wild-type, the mutator mutant L98 and the antimutator mutant CB121 were purified about 100-fold free of foreign enzyme activities interfering with the polymerase assay. The enzymes were characterized as to thermostability, exonuclease activity and kinetic data with DNA template primer, deoxythymidine 5' -triphosphate, and a mixture of all four deoxynucleoside 5' -triphosphates. The effects of eight inhibitors of DNA synthesis on the three enzymes were determined (Schroeder and Jantschak 1978 and 1980, Jantschak and Schroeder 1980) and are compared here. The most selective inhibitor, pyridoxal 5' -phosphate, interacts with the active site of the polymerases while the two least discriminating drugs, distamycin A and actinomycin D, do not directly interact with the polymerases at all. The study was intended to test whether specific enzyme inhibitors elicit a differential response in temperature-sensitive structural variants of this enzyme and whether, in principle, structural variants of virus enzymes or the respective ts- mutants in vivo are suitable as a screening system for selective antiviral agents. PMID- 6267835 TI - Amino acid distribution of cereals in commercial mill products. AB - The amino acid contents of wheat and rice as well as their final products produced by commercial milling were determined quantitatively by the amino acid analyzer. Less quantities of lysine, glycine, arginine, alanine, and aspartic acid were found in the flour, whereas more levels of these amino acids were found in the wheat grain. Conversely, more proline, phenylalanine and glutamic acid were found in the flour, and less amounts of these amino acids were found in the wheat grain. The proportion of the other amino acids were slightly affected by milling. On the other hand, less amounts of aspartic acid, serine, glutamic acid, and proline were found in rice bran and germ, whereas more levels of these amino acids were found in brown and milled rice. Conversely, rice bran and germ contained more threonine and cystine than brown and milled rice. The proportions of the other amino acids were slightly affected by milling, however, high content of lysine in germ was notable. PMID- 6267836 TI - [The effect of prednisolone and ACTH on the in vitro metabolism of human placenta from early pregnancy (author's transl)]. AB - The effects of prednisolone and ACTH on in vitro oxygen consumption and aerobic and anaerobic glycolysis of human placentas of early pregnancy were studied. Oxygen consumption and anaerobic glycolysis were significantly reduced by prednisolone, while ACTH resulted in a significant increase in aerobic glycolysis during the 2 hr experimental period. PMID- 6267837 TI - [The activity of imidazole derivatives in the presence of human plasma (author's transl)]. AB - By Warburg technique using yeasts and staphylococci, any decrease in antimicrobial activity of the imidazole derivatives could be excluded in the presence of human plasma. Econazole nitrate, the classical topical imidazole derivative, and ketoconazole, an oral active antifungal, were tested. The compatibility between imidazole derivatives and human plasma is of practical importance for obtaining optimal therapeutic results in treating human mycoses. PMID- 6267838 TI - [Role of erythrocyte chalone in regulating erythropoiesis]. PMID- 6267839 TI - [Na+-K+-dependent ATPase]. PMID- 6267840 TI - [Results and prospects for experimental studies of the most important Vvedenskii phenomena: parabiosis of a nerve conductor and the minimum frequency for neuromuscular synapses]. PMID- 6267841 TI - [Molecular mechanisms of the effects of botulin in tetanus neurotoxins]. PMID- 6267843 TI - Short-term modulation of domestic pigeon (Columbia livia L.) behaviour induced by intraventricular administration of ACTH. AB - The behavioural responses induced in adult domestic pigeons by intraventricular injections of 0 to 6 IU of ACTH 1-39 are reported. The frequency of 10 different behaviour patterns was recorded for 90 min after administration of the peptide. The effect that was induced was complex, the frequency of some patterns increasing (yawning, headshaking, body shaking, wing-flapping), or some others decreasing (feeding, one-wing stretching, eye closing) or remaining unchanged (preening). The frequency of several patterns was maximal during the first 30 min following the injections but this was shown in some cases to be independent on the hormone administration. PMID- 6267844 TI - [Duration of efficiency of pertussis immunoglobulin in the passive protection tests in mice (author's transl)]. AB - The prophylactical effect of human anti-Pertussis immunoglobulin was shown in a passive protection test in mice over a time of 9 days, which is more than three times the half live time. In the agglutination test one could find a half life time of 64.7 hours; in the neutralisation test, which is the only valuable for the clinical effect, we could find an average value of half life time of 51.6 hours. We found a nearly parallel decrease in both titers. In the view of our results we discussed former clinical trials and the prospects for a future use of anti-Pertussis immunoglobulins in prophylaxis and therapy; in both fields only those preparations should be used, which are tested for clinical efficiency in a neutralisation test. PMID- 6267845 TI - [On the biological action of transition metal complexes. 1. The antiviral activity of palladium aminopyridin-complexes (author's transl)]. AB - Some aminopyridine complexes of palladium and PdCl2 showed an antiviral in vitro activity against enveloped DNA and RNA viruses such as vaccinia virus, pseudorabies virus, NDV and FPV. In contrast, naked RNA virus as mengovirus was not affected. The compounds were compatible for chicken embryo as well as FL cells in concentrations of 100-250 microM. The therapeutical index calculated from the maximally tolerated dose and the concentration causing a 50 per cent plaque reduction was determined with more than 45 for vaccinia virus, for example. PMID- 6267847 TI - [Ultrastructural organization of a bacteriophage isolated from Bordetella pertussis]. PMID- 6267846 TI - Multimodality treatment of malignant gliomas. Comparison of several adjuvant approaches. PMID- 6267848 TI - [Microacupuncture therapy of pain syndromes of the lumbosacral portion of the peripheral nervous system]. AB - Results of clinical and neurophysiological observations of 96 patients treated by the new method of microacupuncture are presented. This method is a modification of classical acupuncture, and consists of implantation of a specially designed micro-needle into the skin for a long time (one to three weeks). Possible mechanisms of the effects of this therapy method on the body are discussed. Recommendations on practical use of the microacupuncture method for treating vertebrogenic radicular syndromes are given. PMID- 6267849 TI - [Use of stimulation electroneuromyography (review)]. PMID- 6267850 TI - [Mono- and polyradicular syndromes in lumbar osteochondrosis]. AB - The authors studied the clinical picture of lumbar osteochondritis in 1,020 patients, 151 of whom were operated on. The monoradicular syndrome was diagnosed in 68%, the biradicular (involvement of two radicles) in 27%, and the polyradicular (involvement of three and more radicles) in 7% of the patients. In the authors' opinion, the development of the mono- or polyradicular syndromes in lumbar osteochondritis depends on the character of the disc hernia (lateral, paramedian, median) and on the degree of the reactive inflammatory changes in the radicles, the epidural tissue and the spinal meninges. Of an importance in this connection is the duration of the disease, especially, of the radicular manifestations. A particular attention should be also paid to the duration of the disease relapse. PMID- 6267851 TI - [Stimulation electromyography in evaluation of radicular disorders in lumbar osteochondrosis]. AB - Using stimulation electromyography the state of the afferent and efferent parts of the reflectory arch was estimated at the lumbosacral level in 93 patients with lingering exacerbations of the syndromes of lumbar osteochondritis. In cases of radicular disturbances a lowering (statistically significant) of the speed of the stimulus transmission along the proximal parts of the motor fibres in the affected radicles was noted. A deterioration of the H-reflex of the musculus soleus pointed to the involvement of the first sacral radicle. PMID- 6267852 TI - [Alcoholic polyneuropathy]. AB - A classification of alcoholic polyneuropathy is offered. This classification was developed by the author on the basis of neurological examinations of 354 alcoholics. Combinations of various disturbances of peripheral innervation (within the limits of a polyneuropathy) both between each other and with various cerebral disturbances are described. As a result, the following forms of the alcoholic polyneuropathy are distinguished: vegetative, sensor, mixed, pseudodiabetic, and motor ones, as well as Korsakov's syndrome. Both the cerebral and the peripheral disturbances are transient: on being developed in the period of the abstinence they gradually subside. PMID- 6267853 TI - Hybridization of restriction fragments derived from calf satellite I DNA. AB - Two DNA fragments, the 643 base pairs (bp) and 621 bp long, obtained by endoR.Pst nuclease digestion of the 1350 bp basic repetitive unit of the calf satellite I DNA and cloning, do not hybridize with each other. Both of them, however, hybridize with the 970 and 1550 bp fragments, the sequence of which has been found to be homologous with that of the satellite I DNA. PMID- 6267854 TI - Cushing's syndrome, due to ectopic ACTH-secretion, successfully treated with aminoglutethimide, radiotherapy and chemotherapy. PMID- 6267855 TI - A three year follow-up study of a patient with a malignant islet cell tumour treated with streptozotocin. PMID- 6267856 TI - Thyroid uptake of 201thallium and its control by TSH. AB - Patients injected with 201Thallium (201Tl) for myocardial scanning present good thyroid visualization. Determinations in mice injected with 201Tl indicated a high thyroid/serum concentration ratio (T/S). The 201Tl biological half-life (t 1/2) in serum (30 - 135 s) was much shorter than in thyroid (53 - 55 h) for human subjects and experimental animals. The 1 h 201Tl T/S ratio was comparable to that of 131I and 99mTc, indicating presence of a gradient for 201Tl also. Increase of endogenous TSH induced by propylthiouracil led to a significant rise in in T/S for 99mTc, 131I and 201Tl, whereas TSH inhibition by feeding l-thyroxine led to decrease in T/S for 99mTc and 201Tl. In vitro thyroid/medium concentration ratio (T/M) of 99mTc and 201Tl was decreased after 20' incubation with ouabain, an inhibitor of the Na+, K+, activated ATP-ase. However, perchlorate in vitro or in vivo failed to diminish the 201Tl T/M ratios or to affect the t 1/2 of 201Tl in human subjects, whereas T/M of 201Tl was depressed by KCl addition to the medium. PMID- 6267857 TI - Properties of human thyroidal and extrathyroidal TSH receptors. PMID- 6267858 TI - Plasma aldosterone response to acute stimulation in panhypopituitarism. AB - The influence of acute stimulation by ACTH, upright posture and angiotensin II on plasma aldosterone levels was assessed in human panhypopituitarism. While stimulation by ACTH in hypopituitary patients induced a plasma aldosterone increase similar to that observed in healthy controls, stimulation by upright posture or by infusion of angiotensin II resulted in a lower plasma aldosterone response than in controls in most of the patients. These results suggest that the presence of an anterior pituitary hormone, most likely ACTH, directly or indirectly exerts a permissive action on aldosterone secretion in man. PMID- 6267859 TI - Corticotrophin stimulation test: inverse correlation between basal serum cortisol and its response to corticotrophin. AB - Serum cortisol response to synthetic corticotrophin (B1-24-ACTH) was evaluated in 21 normal subjects. There was significant negative correlation (r = -0.633, P less than 0.001) between the basal serum cortisol and the increase in serum cortisol level in response to ACTH. Two subjects had an increase in serum cortisol of less than 194 nM/1 (7.0 microgram/100 ml) and two additional subjects had an increase of less than 278 nM/l (10.0 microgram/100 ml). All subjects had an absolute peak value greater than 583 nM/l (21.0 microgram/100 ml) at 30 or 60 min post-ACTH. Inverse correlation between basal serum cortisol and the increase in serum cortisol suggests that in patients who have high basal serum cortisol levels, endogenous ACTH may already have reduced the cortisol reserve of the adrenal gland. PMID- 6267860 TI - Effects of prolonged ACTH treatment on adrenal steroidogenesis and blood pressure in rats. PMID- 6267861 TI - Specific enzyme immunoassay for human chorionic gonadotrophin. AB - A sandwich-type enzyme immunoassay system specific for human chorionic gonadotrophin (hCG) was prepared with the antibody Fab'-beta-D-galactosidase complex and the antibody F(ab')2-immobilized silicone rubber solid phase by using a purified antibody to beta subunit of hCG (hCG beta). The assay system cross reacted less than 4% with human luteinizing hormone (hLH) and human follicular stimulating hormone (hFSH), and proved to be highly sensitive with hCG measurable at levels as low as 0.3 mIU per assay tube. Using 50 microliter of serum sample, 6-600 mIU/ml of hCG in serum could be determined specifically with the same degree of precision as in radioimmunoassay but without sample interference with the assay. The coefficients of variation within-run and between-run were 8.6 8.9%, and 4.9-10.7%, respectively. Values obtained with the enzyme immunoassay correlated well with those of radioimmunoassay (r = 0.98, slope = 0.94, y intercept = 10.2 mIU/ml for 75 serum samples). Results of the immunoassay of hCG levels in serial samples of serum from healthy women and patients with choriocarcinoma show that this method is useful in the clinical diagnosis of trophoblastic disease. PMID- 6267862 TI - [Paraneoplastic syndromes. Clinical and epidemiological contribution]. PMID- 6267864 TI - [A case of cerebellar syndrome in a subject with bronchial carcinoma]. PMID- 6267863 TI - [Nervous system lesions in subjects with malignant neoplasms]. PMID- 6267865 TI - [An unusual case of polyneuropathy in a patient with a malignant intracranial melanoma]. PMID- 6267866 TI - [Familial amyloidosis polyneuropathy. Description of a case]. PMID- 6267867 TI - [Hereditary neuropathy with a tendency to compression paralysis. Electrophysiological, morphometric and ultrastructural study of 2 familial cases]. PMID- 6267868 TI - [Further data on peripheral nerve complications of arteriovenous fistulas in uremic patients on hemodialysis]. PMID- 6267870 TI - In vitro release of steroids from the human fetal adrenal tissue. AB - Human fetal adrenal glands obtained at mid-gestation were incubated in vitro, and steroids in the incubation media and tissues were measured by radioimmunoassay. During two consecutive one-hour incubation periods, mean concentrations of 2.23+/ 0.45 and 2.77+/-0.60 ng/h/mg tissue (+/-SE) of combined pregnenolone and pregnenolone-sulfate were found in the media of the control group. When adrenocorticotropin (ACTH) was added in the second half of incubation, the total pregnenolone level rose from an average of 1.90+/-0.42 to 5.89+/-2.00 ng/h/mg tissue (p less than 0.05). The dehydroepiandrosterone (DHA) and DHA-sulfate levels in the control media remained almost unchanged, while the addition of ACTH caused a significant increase, from 6.26+/-1.48 to 15.49+/-4.08 ng/h/mg tissue (p less than 0.05). The tissue content of these steroids increased slightly but not significantly in the ACTH group. Lesser amounts of 16 alpha-hydroxy-DHA and 16 alpha-hydroxy-DHA-sulfate, progesterone and cortisol were also measured in both incubation media and tissue. Concentrations of these steroids did not change significantly upon the addition of ACTH in vitro. This in vitro study further supports the hypothesis that the fetal pituitary-adrenal axis has the potential to respond to stress-induced ACTH release and secretes steroids which are the precursors of sex steroids in pregnancy. PMID- 6267869 TI - Storage of lipofuscin in neurons in mucopolysaccharidosis. Report on a case of Sanfilippo's syndrome with histochemical and electron-microscopic findings. AB - A histochemical and ultrastructural study was made on the brain of a 23-year-old man with Sanfilippo's syndrome. In accordance with previous reports the cortical nerve cells contained a PAS-positive lipid storage substance. This showed intense autofluorescence in UV-light and was positive with various stains for lipofuscin. The storage material appeared ultrastructurally as inclusion bodies composed of short lamellated membranes, granular material, and vacuoles. In addition, concentrically and transversely lamellated membranous cytoplasmic bodies were observed in the nerve cells. It is concluded that the PAS-positive lipid storage material in the neurons was composed partly of lipofuscin in addition to other lipids presumably glycosphingolipids. PMID- 6267871 TI - Adrenal steroids, bone mineral content and endometrial pathology in postmenopausal women. AB - In 19 postmenopausal women, basal serum levels of cortisol, unconjugated dehydroepiandrosterone (DHA), dehydroepiandrosterone sulphate (DHAS), testosterone and unconjugated and total estrone were measured both before and during an ACTH test. A positive correlation was found both between basal levels of DHAS and the DHA response to ACTH, respectively, and trabecular bone mineral content of the distal forearm. A significant correlation was also observed between bone mineral content and precancerous/cancerous states of the uterine epithelium. PMID- 6267872 TI - Familiar non-chromaffinic paragangliomas (glomus tumors). Clinical and genetic aspects (abridged). AB - The presence of glomus tumors in a large family was investigated by clinical and angioscintigraphic screening methods. Of 295 members of this family 162 persons participated in the study. A total of 47 tumors of the head and neck region were found in 26 patients. The study revealed a preponderance for the male sex, a fairly equal distribution of the different locations in the head and neck and a marked tendency towards multiplicity. The inheritance is autosomal dominant, with a clear increase of the penetrance with age. PMID- 6267873 TI - Analysis of the results of our combined therapy for maxillary cancer. AB - The study was performed in 70 patients with maxillary cancer to evaluate how far the long-term survival rate of the maxillary cancer can be improved with maximum combination of radiation therapy using 6 mV Linac X-ray, intra-arterial chemotherapy using 5-fluorouracil, sufficiently extensive maxillectomy and primary reconstruction. In 52 cases of squamous cell carcinoma, the 3-year and 5 year actual survival rates were 85.2% and 71.1% respectively. In the total 70 cases including those of undifferentiated carcinoma and adenocarcinoma, the 3 year and 5-year actual survival rates were 75.2% and 64.1% respectively. Primary reconstruction, which consisted chiefly of covering the entire wound surface with the deltopectoral flap, enabled us to perform as much resection of the subcutaneous tissue of the facial skin, tissue around the mandible and cranial base as necessary, without consideration of the postoperative facial disfigurement and functional impairments. PMID- 6267874 TI - Inborn errors of purine catabolism. PMID- 6267875 TI - Myofibroblasts in fibrous tumors and fibrosis in various organs. AB - The morphology and population of myofibroblasts detected by electron microscopy in fibrous tumors and fibrosis in various organs have been examined. The myofibroblast was identified by characteristic features of the indented nucleus, bundles of abundant microfilaments with dense bodies, focal basal lamina and well developed rough endoplasmic reticulum. It has been observed that myofibroblasts in a variety of fibrous tumors and fibrosis appeared predominantly in fibromatosis and reparative process of deep fibrous tissues and organs particularly in the lesions involving the fascia and subcutaneous tissue. It was suggested that myofibroblasts would be modified fibroblasts to which fibroblasts in the fascia and deeply situated fibrous tissue transformed during proliferation and differentiation. PMID- 6267876 TI - Localized hepatic necrosis related to cytomegalovirus and Toxoplasma gondii. AB - An unusual hepatic lesion due to both cytomegalovirus and Toxoplasma gondii was described in a patient with angio-immunoblastic lymphadenopathy treated by predonin. The lesion was a single well-defined area measuring 1.5 x 1.0 x 0.5 cm of confluent severe hepatic necrosis with multiple cytomegalic inclusion cells and numerous tokoplasmas. The remaining liver had no liver cell necrosis, inflammatory cell infiltration, or evidence of either cytomegalovirus infection or toxoplasmosis. These findings suggested us the possibility of symbiosis and synergism of cytomegalovirus and toxoplasma gondii in the liver. Additionally, this was the first demonstration of cytomegalovirus in liver cells by electron microscopy. PMID- 6267877 TI - The release of neurohypophysial hormones as influenced by stimulation of alpha adrenergic transmission in long-term dehydrated male white rats. Information 1: hypothalamic and neurohypophysial vasopressor activity. AB - Rats dehydrated up to 12 days were given intraperitoneally methoxamine hydrochloride in a daily dose of 1.0 mg/100 g of the initial body weight. The single dose of methoxamine administered to normally hydrated animals was followed by a significant increase of the vasopressin content of the neurohypophysis and hypothalamus (both in NSO and NPV regions). Under conditions of severe dehydration a more marked depletion of hypothalamic and neurohypophysial vasopressin stores was noted in methoxamine-treated animals. PMID- 6267878 TI - The release of neurohypophysial hormones as influenced by stimulation of alpha adrenergic transmission in long-term dehydrated male white rats. Information 2: hypothalamic and neurohypophysial oxytocic activity. AB - Rats dehydrated up to 12 days were given intraperitoneally methoxamine hydrochloride in a daily dose of 1.0 mg/100 g of initial body weight. The only dose of methoxamine injected into normally hydrated animals did not influence significantly the oxytocic activity neither in the hypothalamus nor in the neural lobe. Following four days of dehydration a distinctly more marked depletion of the hypothalamic (both in the NSO and NPV region) and neurohypophysial oxytocin content was found in animals treated with methoxamine. For the neurohypophysis, a similar effect has been noted under severe dehydration (8th and 12th day) as well. PMID- 6267880 TI - Iohexol. A non-ionic contrast medium. Pharmacology and toxicology. PMID- 6267879 TI - The effect of certain electrolytes on neuromuscular transmission disturbances evoked by direct action of phospholine on synaptic structures. AB - In an isolated preparation of rat diaphragm stimulated indirectly (12 impulses per minute) after total inactivation of acetylcholinesterase phospholine reduced the amplitude of the response proportional to its concentration. The rise in the concentration of potassium, magnesium or calcium in the incubation fluid failed to alleviate the disturbances produced by phospholine. Phospholine increased significantly reduction of response amplitude caused by increased calcium and magnesium concentration and increased to a small extent response depression caused by raised potassium concentration. The obtained results, point out that phospholine exerts a direction on the neuromuscular junction which is connected with the postsynaptic action of this agent. PMID- 6267881 TI - Effect of angiographic contrast media on the liver. II. Biliary excretion of iohexol in the anuric rabbit. PMID- 6267882 TI - Effect of iohexol on human erythrocytes. I. Changes of red cell morphology in vitro. PMID- 6267883 TI - Effect of iohexol on human erythrocytes. II. Red cell aggregation in vitro. PMID- 6267884 TI - Effect of iohexol on red cell deformability in vitro. PMID- 6267886 TI - Tolerance and excretion of iohexol after intravenous injection in healthy volunteers. Preliminary report. PMID- 6267885 TI - Effect of iohexol, metrizamide and ioxaglate on the blood-brain barrier. AB - The effect upon the blood-brain barrier of the non-ionic contrast medium iohexol, compared with that of ioxaglate and metrizamide, was analysed. The contrast media were injected selectively into the internal carotid arteries of rabbits, and 197Hg Ac2 and Trypan blue were used as markers for evaluation of the injury. Less injury to the blood-brain barrier was caused by iohexol. PMID- 6267888 TI - Coronary angiography with iohexol and other contrast media in the dog. II. Left ventricular contractility and work. AB - At left coronary angiography in the dog the non-ionic media iohexol, 711 and metrizamide caused a similar reduction of the left ventricular pressure, stroke volume and work as Na/Ca/meglumine metrizoate but less than diatrizoate. After the initial reduction all media produced equal increase in the data, exceeding their preinjection levels. The calcium ameliorating the reduced cardiac function produced by metrizoate did not seem to impose an extra load on the left ventricle during the second phase. PMID- 6267887 TI - Coronary angiography with iohexol and other contrast media in the dog. I. Electrocardiographic alterations. AB - In the dog the effects on ECG at coronary angiography with the non-ionic contrast media iohexol and metrizamide and the ionic medium diatrizoate were compared. Iohexol and metrizamide produced less prolongation of the PQ time during left sided infusions and less prolongation of the QT time during right-sided infusions. Thus, as a cardiovascular contrast medium iohexol may cause fewer incidences of heart block and ventricular fibrillation than ionic contrast media. PMID- 6267889 TI - Coronary angiography with iohexol and other contrast media in the dog. III. Contractility of the left ventricle. AB - Compared with the ionic contrast medium diatrizoate the new non-ionic media iohexol and 711 produced significantly less reduction of contractile force, left ventricular pressure and the first derivative of left ventricular pressure during left coronary angiography in the dog. These two media may be expected to have similar effects on the function of the myocardium as metrizamide. PMID- 6267890 TI - Cardiovascular effects of iohexol in the rat and the isolated rabbit heart. AB - The haemodynamic and cardiac side effects of the new non-ionic contrast medium, iohexol, were investigated anaesthetized rats and isolated perfused rabbit hearts. Iohexol, caused a positive inotropic response in both models, elevated coronary flow and in high doses had an inhibitory influence on the cardiac conducting system. From a comparison with Amipaque and Urografin 76 it was concluded that with respect to cardiac side effects iohexol can be ranked between these media. PMID- 6267891 TI - Aortic and pulmonary arterial pressure after injection of contrast media into the right atrium of the rabbit. Comparison between metrizoate, ioxaglate and iohexol. AB - Effects in cardioangiography from injections into the right atrium of rabbits of two new contrast media of low osmolality, one non-ionic (iohexol) and one ionic dimeric (ioxaglate), were recorded and compared with a currently used ionic contrast medium (metrizoate) of high osmolality. Iohexol and ioxaglate produced significantly smaller increase in pulmonary arterial pressure than metrizoate. Also in aortic pressure iohexol and ioxaglate induced smaller changes (compared with the injection of the same volume of saline) than metrizoate. PMID- 6267892 TI - Effect of contrast media on femoral blood flow. Comparison between non-ionic and ionic monomeric and monoacidic dimeric contrast media in the dog. AB - Injections of non-ionic monomeric (metrizamide, C29 and iohexol) and monoacidic dimeric (ioxaglate) contrast media into the femoral artery of dogs caused significantly less increase in the rate of femoral blood flow than the more hypertonic ionic monomeric compound metrizoate at equivalent iodine concentrations. The effect of metrizoate was similar to that of equiosmolal solutions of sodium chloride. Sodium chloride in concentrations equiosmolal with the non-ionic monomers and monoacidic dimer caused less changes in blood flow than these contrast media, but the changes in blood were equal to those of isotonic sodium chloride. PMID- 6267893 TI - Proteinuria following nephroangiography. VII. Comparison between ionic monomeric, monoacidic dimeric and non-ionic contrast media in the dog. AB - The degrees of albuminuria induced by nephroangiography in dogs with the ionic monomeric contrast medium diatrizoate, the non-ionic iopamidol, iohexol and C29 and the monoacidic dimeric contrast medium ioxaglate were compared. Diatrizoate induced significantly higher albuminuria than the other contrast media. No significant differences in the degree of albuminuria following angiography were found between iopamidol, iohexol, C29 and ioxaglate. PMID- 6267894 TI - Proteinuria following nephroangiography. VIII. Comparison between diatrizoate and iohexol in the rat. AB - The degrees of albuminuria induced by nephroangiography in rats with the ionic contrast medium diatrizoate and the non-ionic contrast medium iohexol were compared. Iohexol induced significantly less albuminuria than diatrizoate following angiography. PMID- 6267895 TI - Acute intravenous toxicity of iohexol in the mouse and in the rat. AB - Iohexol has been shown to have a remarkably low intravenous toxicity in mice and rats. It has an even lower toxicity than metrizamide which previously has been shown to be better tolerated than the common ionic media. PMID- 6267896 TI - Tolerance to iohexol after intracisternal, intracerebral and intraarterial injection in the rat. PMID- 6267897 TI - Excitation and depression of non-anaesthetized rabbits following injection of contrast media into the subarachnoid space. PMID- 6267898 TI - Pharmacokinetics and biotransformation of iohexol in the rat and the dog. PMID- 6267899 TI - Iohexol. PMID- 6267900 TI - Excretion of urographic contrast media. I. Iohexol and other media during free urine flow in the rabbit. PMID- 6267901 TI - Excretion of urographic contrast media. II. Ioxhexol and sodium diatrizoate during ureteric stasis in the rabbit. PMID- 6267902 TI - Gamma camera emission tomography. Development and properties of a multi-sectional emission computed tomography system. PMID- 6267903 TI - Connections of the hypothalamus and preoptic area with nuclei of the amygdaloid body in the rat; HRP retrograde transport study. AB - Horseradish peroxidase (HRP) was injected into various nuclei of the amygdala in 50 rats. The retrograde axonal transport of HRP showed various connections arising from the hypothalamic nuclei and the basal forebrain. Neurons of the magnocellular preoptic nucleus send out amygdalopetal axons to all amygdaloid nuclei except the lateral nucleus. The amygdalopetal projections emerge from the large neurons situated dorsally in the most lateral preoptic area (probably substantia innominata) and terminate in the basal dorsal and the central amygdaloid nuclei. Neurons in the lateral division of the hypothalamus (the lateral hypothalamic area proper and the perifarnical region) send out axons which terminate in the medial and central nuclei and in the posterior part of the cortical amygdaloid nucleus. Axons emerging from the ventromedial hypothalamic nucleus end mainly in the medial nucleus and in the central amygdaloid nucleus. Amygdalopetal fibers arising from neurons of the ventral premammillary and dorsal hypothalamic nuclei reach the medial amygdaloid nucleus and perhaps a few of them end in the posterior part of the cortical amygdaloid nucleus. Neurons of the bed nucleus of the stria terminalis project to the medial, the posterior part of the cortical and probably to the basal dorsal amygdaloid nuclei. PMID- 6267904 TI - Subcortical connections of the prefrontal cortex in dogs: afferents to the proreal gyrus. AB - Afferent subcortical connections to the proreal gyrus of the prefrontal cortex (PFC) in the dog were investigated using the horseradish peroxidase retrograde transport method. The afferent projections derive mainly from dorsal-intermediate and caudal regions of the mediodorsal nucleus (MD), from $he ventral as well as from the lateral thalamic nuclei. In the ventral nuclei, the distribution of labeled cells showed a topography correlated with injections localized in the anteroposterior direction. Furthermore, single cells were labeled in midline and intralaminar thalamic nuclei as well as some extrathalamic structures. The data obtained in behavioral and anatomical experiments with dog and monkey are discussed. The distribution of afferent projection from MD and the functional division on particular subfields of PFC seems to be in accordance in both species. PMID- 6267905 TI - Malignant gliomas - glioblastoma multiforme and astrocytoma III-IV with extracranial metastases. Report of two cases. AB - The authors describe two rate cases of extraneural metastases of glioblastoma multiforme and of astrocytoma III-IV, but with different distribution routes. In the first case - astrocytoma III-IV - via the lymphatic system, with metastases in the cervical lymph nodes; in the second case-glioblastoma-via the blood system, with metastases in the sternum and vertebrae. Survival times were 18 months in the astrocytoma case (operation plus irradiation), and 6 months in the glioblastoma case (operation, irradiation, and chemotherapy). The discussion deals with the possible paths of the metastases, the connection between metastatic spread and survival time (in the longer surviving patient the metastases were discovered together with the recurrence), and problems in deciding the individual therapy. PMID- 6267906 TI - Angiotensin-converting enzyme inhibitors: pathogenic and therapeutic implications for arterial hypertension. PMID- 6267907 TI - The glomerulus: site of synthesis and target for hormones and chemical mediators. PMID- 6267908 TI - Endocrine disorders in chronic hemodialysis patients (with the exclusion of hyperparathyroidism). PMID- 6267909 TI - Control of renal blood flow in essential hypertension. PMID- 6267910 TI - The molecular genetics of thalassemia. PMID- 6267912 TI - A superoxide-activated chemotactic factor and its role in the inflammatory process. AB - Superoxide dismutase or derivatives thereof have been shown to be potent anti inflammatory agents in several models of induced inflammation. In all cases, the anti-inflammatory effects included a marked suppression of the accumulation of inflammatory cells at the site of the potential lesion, suggesting a role for the superoxide radical in the chemotaxis process. The exposure of normal plasma to a source of superoxide in vitro resulted in the formation of a powerful chemotactic factor for human neutrophils. The factor is activated by reacting specifically with superoxide, and was found to consist of a complex of serum albumin and an unidentified lipid. The complex may be resolved and reconstituted. Both components are required for expression of biologic activity. The major mechanism for the anti-inflammatory activity of superoxide dismutase appears to be the prevention of the formation of this plasma-derived superoxide-dependent chemotactic factor. PMID- 6267913 TI - Lipoxygenase products and the polymorphonuclear leucocyte. AB - Polymorphonuclear leucocytes (PMNs), when exposed to the calcium ionophore A23178, release into the supernatant a substance that causes the aggregation and chemokinesis of fresh PMN suspensions. Release of these activities is inhibited by preincubation with drugs known to inhibit lipoxygenase pathways of arachidonic acid metabolism but is unaffected by cyclooxygenase inhibitors. The substance responsible for these activities has been identified as leukotriene B and this compound has been shown to be a potent chemokinetic and aggregatory agent for PMNs over the range 10 pg to 5 ng ml-1. PMID- 6267911 TI - Cell-to-cell interactions in the secretion of enzymes of connective tissue breakdown, collagenase and proteoglycan-degrading neutral proteases. A review. AB - Cell and tissue culture techniques provide valuable tools for investigating cell to-cell interactions leading to the secretion of connective-tissue degrading enzymes, collagenase and proteoglycan-degrading neutral proteases, in inflammatory situations. These interactions, which might constitute a major regulatory mechanism, are reviewed here. Taken together, the available data strongly suggest that fibroblasts and related mesenchymal cells (such as chondrocytes, fibroblast-like or type B synovial lining cells, corneal stromal cells, etc.) could be the main suppliers of collagenase within tissues. These cells can secrete collagenase in response to factors produced by other cells, mainly macrophages and related cells (monocytes, synovial cells - presumably the macrophage like, type A synovial lining cells), possibly also epithelial cells. Lymphocytes are able to modulate factor production by macrophages so that, through the macrophage link the secretory behavior of the fibroblastic cells may be under the control of the immune defense system and serve as an effector of immune reactions leading to connective tissue destruction. PMID- 6267914 TI - Cyclic nucleotides, possible intracellular mediators of macrophage activation and secretory processes. AB - Macrophages from various sources can be stimulated by a variety of substances to secrete a range of inflammatory mediators and degradative enzymes. The mechanisms involved in the activation and secretory processes are unknown, However, recent evidence suggests that cyclic AMP may play a role in the regulation of neutral protease secretion. Thus, it has been shown that agents known to increase intracellular cyclic AMP levels (cyclic AMP analogues, phosphodiesterase inhibitors, prostaglandin E1 and E2, catecholamines, cholera toxin and, indirectly, glucocorticosteroids) inhibit the secretion of the neutral protease plasminogen activator. It is speculated that macrophage activation may also initiated by changes in the steady-state levels of cyclic nucleotides. A decrease in intracellular cyclic AMP and/or an increase in cyclic GMP levels would favour secretion. It is possible that these changes could be brought about by the action of various stimuli to modify the capacity of the macrophage to synthetize or degrade cyclic nucleotides. PMID- 6267915 TI - Cyclic AMP in macrophages from experimental granulomas and the effect of prostaglandin E2. AB - Leucocytes were isolated by pronase digestion from granuloma tissue at different stages in inflammation induced by carrageenin-soaked sponge implants in rats and cyclic AMP was measured in these cells. In a mixed cell suspension, containing granulocytes and macrophages, the cyclic AMP levels increased during the early stages of inflammation but decreased when the granuloma became established. However, after correction for the proportion of infiltrating macrophages, as the inflammation progressed only a fall in cyclic AMP content was observable. Exposure of granuloma-derived cells to PGE2 resulted in a rise in cyclic AMP content, which was more pronounced in cells isolated during a later rather than an earlier stage of granuloma development. The results provide support for the earlier proposal that the anti-inflammatory effect of E-type prostaglandins on granulomas is partially explicable on the basis of cyclic AMP changes in infiltrating macrophages. PMID- 6267916 TI - Variations in levels of cyclic AMP and GMP in the thymus, spleen and mesenteric lymph node of rats after the induction of adjuvant arthritis. AB - The development of adjuvant arthritis induced important modifications in intracellular levels of cyclic AMP and GMP in primary and secondary lymphoid organs: a continuous decrease in cyclic AMP and a biphasic increase in the level of cyclic GMP which correlate well with the onset of the acute phase and the systemization of the disease. PMID- 6267917 TI - Effects of vasoactive and inflammatory agents on cyclic AMP levels in W138 fibroblasts, endothelial and vascular smooth muscle cells in culture. AB - The vasoactive amines noradrenaline, histamine and 5-hydroxytryptamine and the beta-adrenergic agonist, isoproterenol, had no effect on porcine aortic endothelial or smooth muscle cell cyclic AMP, but these amines increased the level of cyclic AMP in W138 fibroblasts. PGE1, PGE2 and PGI2 were also without effect on endothelial or smooth muscle cells, while increasing WI38 cell cyclic AMP. PGF2 alpha and 6-oxo-PGF1 alpha had no effect on all three types of cell. Inhibition of endogenous prostaglandin production by the cells, using aspirin, did not affect the basal levels of cyclic AMP or the subsequent responses to added prostaglandins in all three cell types. PMID- 6267918 TI - [Dysfunction of beta-receptor in atopic disorders of the conjunctiva (author's transl)]. PMID- 6267919 TI - Differential effects of systemic and intracoronary calcium channel blocking agents on global and regional left ventricular function in conscious dogs. AB - We examined the differential effects of intravenous (IV) equimolar doses of diltiazem (D), verapamil (V), and nifedipine (N) upon left ventricular (LV) function in 12 healthy unsedated dogs. We also attempted to isolate direct myocardial effects of these agents from reflex and peripheral effects by using intracoronary (IC) equimolar drug administration in an additional six animals. Despite equivalent dose-related increases in heart rate and declines in arterial pressure intravenous V (0.04, 0.1, 0.17 mg/kg) and N (0.3 mg/kg) but not D (0.04, 0.1, 0.17 mg/kg) depressed LV function. Peak effects after high dose V included increased heart rate (HR) (68%) and reduced mean aortic pressure (MAP) (17%), dP/dt max (22%), and percent shortening of the LV minor diameter (% delta D) (33%) (all p less than or equal to 0.001). By contrast, equimolar D increased HR (68%) and decreased MAP (20%) but produced no change in dP/dt or % delta D while low dose N (0.03 mg/kg) depressed dP/dt and % delta D by 37% and 45%, respectively (both p less than or equal to 0.001) despite similar changes in HR and MAP. Pretreatment with propranolol (2 mg/kg) and matching HR and loading conditions to control failed to uncover myocardial depression after D. Equimolar IC D, V (4, 8, 16 micrograms/kg), or N (3 micrograms/kg) each produced dose related reductions in percent regional shortening which were greatest with N (58% at 3 micrograms/kg) and least with D (9% at 16 micrograms/kg). These data suggest that calcium channel blockers vary in their propensity to reduce LV function and that the myocardial depressant effects of these agents are partially offset by reflex and peripheral vascular actions. PMID- 6267920 TI - Effect of verapamil on conduction delay produced by myocardial ischemia and reperfusion. AB - Changes in conduction times induced by ischemia (delta CT) have been shown to be quantitatively related to genesis of spontaneous ischemic ventricular fibrillation (VF). We studied conduction delay encountered by premature impulses in epicardium and endocardium in both anterograde and retrograde directions during ischemia and reperfusion in eight control and in eight verapamil treated dogs. Acute myocardial ischemia was produced by single-stage ligation of left anterior descending artery below second diagonal initially, and 30 minutes later below first diagonal branch. In treated dogs, verapamil was given, 0.15 mg/kg intravenous bolus, immediately after first ligation and was followed by an infusion of 7.5 micrograms/kg/min. Thus post-treated segment and pretreated segment were obtained in the same animal. delta CT was compared between control and treated dogs in four myocardial zones: (1) normal, (2) ischemic including pre and post-treated segments, (3) reperfused, and (4) border of reperfusion or ischemia. Results showed that ischemia-induced conduction delay was significantly less in verapamil treated dogs throughout period of ischemia and reperfusion, both in epicardium and endocardium. In addition, in the border of ischemia retrograded conduction showed significantly less depression during ischemia and reperfusion. The protective effect of verapamil was impressive both in pretreated and post-treated segments of ischemic myocardium. We conclude that verapamil offers significant protective action with regard to ischemia-induced conduction delay. Since delta CT is quantitatively related to ischemic VF, verapamil can be antiventricular fibrillatory in myocardial ischemia. PMID- 6267921 TI - Myocardial membrane function and drug action in heart failure. PMID- 6267922 TI - Management of refractory congestive heart failure with prazosin. AB - The cardiocirculatory actions of prazosin (PZN) orally were evaluated by cardiac catheterization, forearm plethysmography, echocardiography, treadmill exercise, and symptoms in patients with advanced long-standing congestive heart failure (CHF). PZN orally (2 to 7 mg) reduced forearm venous tone and decreased forearm vascular resistance. Concomitantly mean systemic arterial pressure declined, left ventricular filling pressure (LVFP) decreased, and cardiac index (CI) was raised. These effects of a single dose of PZN on LV function were rapid in onset, maximal at 1 hour, and sustained for the entire 6 hours of observation. After 2 weeks of outpatient therapy with 2 to 7 mg PZN four times daily, echographic LV end diastolic dimension decreased and the duration of treadmill exercise increased. Symptoms (dyspnea, fatigue, angina) were diminished throughout the course of PZN therapy, and New York Heart Association functional class improved for III to II. Thus PZN possesses sustained nitroprusside-like balanced dilator actions on the systemic arterial and venous beds, which are effectively translated into beneficial hemodynamics of augmenting lowered cardiac output and relieving excessive LVFP. Delayed vasodilator tolerance, occurring in 30% of patients, is prevented by prior use of aldosterone antagonists and is easily treated. Subacute hemodynamic suppression of beneficial PZN vasodilator actions is transient and does not preclude successful sustained PZN therapy of severe chronic CHF. PMID- 6267923 TI - Quantitative radionuclide angiography in assessment of hemodynamic changes during upright exercise: observations in normal subjects, patient with coronary artery disease and patients with aortic regurgitation. AB - Quantitative radionuclide angiography (with the first pass technique and a computerized multicrystal camera) was used to evaluate hemodynamic changes in three subject groups during symptom-limited upright exercise. The 12 normal subjects had significant increases in heart rate, stroke volume, left ventricular ejection fraction and cardiac output during exercise; changes in end-diastolic and end-systolic volumes were not significant. In the 24 patients with coronary artery disease there were significant increases in heart rate and cardiac output during exercise, but insignificant changes in end-diastolic, end-systolic and stroke volumes and ejection fraction. The change in diastolic volume in these patients was determined by the extent of coronary artery disease, propranolol therapy, end point of exercise and presence of collateral vessels. Furthermore, patients with previous myocardial infarction had a lower ejection fraction and higher end-diastolic and end-systolic volumes during exercise than those without myocardial infarction. In the 12 patients with chronic aortic regurgitation of moderate to severe degree, there was a decrease in the end-diastolic volume during exercise. This response was distinctly different from that of the normal subjects or the patients with coronary artery disease. All three groups had a significant decrease in pulmonary transit time during exercise. It is concluded that changes in cardiac output in normal subjects during upright exercise are related to augmentation of stroke volume and tachycardia, whereas in patients with coronary artery disease they are related mainly to tachycardia. Left ventricular dilatation during exercise occurred in some normal subjects and in patients with coronary artery disease but was not a consistent finding. However, a decrease in left ventricular end-diastolic volume is common in patients with aortic regurgitation. Such a decrease may be explained by a reduction in the regurgitant volume per beat caused by shortening of the diastolic filling period or a decrease in systemic vascular resistance, or both. PMID- 6267924 TI - Normal left ventricular emptying in coronary artery disease at rest: analysis by radiographic and equilibrium radionuclide ventriculography. AB - The volume ejected early in systole has been proposed as an indicator of abnormal left ventricular function that is present at rest in patients with coronary artery disease with a normal ejection fraction and normal wall motion. The volume ejected in systole was examined by calculating the percent change in ventricular volume using both computer-assisted analysis of biplane radiographic ventriculograms at 60 frames/s and equilibrium gated radionuclide ventriculograms. Ventricular emptying was examined with radiographic ventriculography in 33 normal patients and 23 patients with coronary artery disease and normal ejection fraction. Eight normal subjects and six patients with coronary artery disease had both radiographic ventriculography and equilibrium gated radionuclide ventriculography. In all patients, there was excellent correlation between the radiographic and radionuclide ventricular emptying curves (r = 0.971). There were no difference in the ventricular emptying curves of normal subjects and patients with coronary artery disease whether volumes were measured by radiographic or equilibrium gated radionuclide ventriculography. It is concluded that the resting ventricular emptying curves are identical in normal subjects and patients with coronary artery disease who have a normal ejection fraction and normal wall motion. PMID- 6267925 TI - Measurement of normal left atrial function with gated radionuclide angiography. AB - A method is described for measuring relative left atrial volume changes with gated radionuclide angiography, using an approximate computer-generated functional image to locate the atrial region of interest. M mode echocardiographic measurements of left atrial and left ventricular distances from the chest wall allowed calculation of a correction factor for the differential attenuation of atrial and ventricular photons. Background-corrected left atrial time-activity curves obtained from normal subjects exhibited excellent temporal resolution and were used to identify and quantitate the reservoir and contractile phases of left atrial volume change. In 20 normal subjects, the mean (+/- standard deviation) value for left atrial fractional emptying was 0.39 +/- 0.07. Expressed as fractions of the left ventricular stroke volume, mean values of the specific phases of atrial volume change were (1) reservoir volume 0.25 +/- 0.09, (2) contractile volume 0.29 +/- 0.10, and (3) conduit volume 0.46 +/- 0.12. PMID- 6267926 TI - Verapamil in chronic stable angina: amelioration of pacing-induced abnormalities of left ventricular ejection fraction, regional wall motion, lactate metabolism and hemodynamics. PMID- 6267927 TI - The inhibitory effect of bran on iron absorption in man. AB - The effects of whole wheat bran and its components on the absorption of nonheme dietary iron were measured using a double isotope technique in human volunteers. When 12 g bran was added to a light meal, absorption decreased by 51 to 74%; this inhibitory effect of bran was shown for meals of both high and low iron availability. Inhibition was not explained by monoferric phytate, the major form of iron in bran, because labeled iron from monoferric phytate was absorbed at least as well as the common pool of nonheme dietary iron. Furthermore, removal of phytate from bran by endogenous phytase did not in itself alter the inhibitory effect of the bran on iron absorption. Studies in which dephytinized bran was separated into a soluble, phosphate-rich fraction and an insoluble, high-fiber fraction indicated that the soluble fraction was more inhibitory than the insoluble fraction. PMID- 6267928 TI - Water-soluble fiber. PMID- 6267929 TI - Diagnosis of acute hepatitis A by HAVAB-M, a direct radioimmunoassay for IgM anti HAV. AB - A three-step solid-phase radioimmunoassay, HAVAB-M, was developed for use in clinical labs as an aid to diagnosing hepatitis A. Polystyrene beads were coated with anti-human IgM (mu-chain specific) and were incubated successively with serum specimen, HAV, and anti-HAV 125I. HAVAB-M was used to assay sera from patients with hepatitis A and was found to have high sensitivity for the IgM antibody to HAV. The antibody was detectable within a few days of onset of symptoms of hepatitis, and it reached maximum concentrations within one to three weeks. The test was designed so that most patients' sera would become negative approximately three months after onset. HAVAB-M was shown to be specific for IgM antibody, with virtually no detection of IgG anti-HAV. The test showed no interference fro rheumatoid factor and no cross-reactivity with sera from patients with hepatitis B or other infectious diseases. PMID- 6267930 TI - Hepatoma in siblings with progressive familial cholestatic cirrhosis of childhood. AB - This report describes four siblings affected with familial intrahepatic cholestasis detected in early infancy. In the two male siblings, biliary cirrhosis and fatal hepatocellular carcinoma later developed, whereas the female siblings have had persistent hepatomegaly and recurrent episodes of cholestasis. Sequential biopsies show that this rare disorder of unknown etiology must be added to the many causes of giant cell transformation of the liver in infancy. Its oncogenic risk, particularly in males, has not been generally appreciated. PMID- 6267931 TI - Specific binding proteins for human chorionic gonadotrophin in a patient with trophoblastic disease. AB - Human chorionic gonadotrophin (hCG) is present in high concentration in patients with trophoblastic disease. The hCG concentration parallels tumor activity. The first known case of an endogenous binder for hCG in the serum of a patient with trophoblastic disease is reported. The patient's hCG concentration was not detectable when analyzed by a radioimmunoassay using a double antibody method; however, it was positive by a radioimmunoassay using polyethylene glycol precipitation. A high serum blank was also observed in this patient. This led the authors to suspect the presence of an endogenous binder for hCG. Scatchard analysis of the patient's serum revealed a high affinity binder with Ka = 1 x 10(10) M(-1), concentration of binding site = 2 x 10(-11) M. This investigation strongly suggested a specific binder(s) for hCG in the serum of this patient. PMID- 6267932 TI - Reactive fibrohistiocytic proliferation simulating fibrous histiocytoma. AB - A pelvic nodule was excised at the time of reexploration of the abdomen in a 32 year-old women who had previously had a malignant germ cell tumor with a mixed histologic pattern of the right ovary. The 3-cm firm lesion from the right vaginal apex was composed predominantly of spindle cells with a prominent storiform pattern. Some findings, such as the presence of foamy histiocytes and a focal foreign body reaction with polarizable material, were atypical for a lesion otherwise quite acceptable histologically as a fibrous histiocytoma. Ultrastructural findings also tended to support the reactive rather than neoplastic nature of this mass. There is a similarity to the silica reaction described by Weiss and co-workers (Cancer 42:2738-2743, 1978). PMID- 6267933 TI - Leukocyte response in childhood infectious mononucleosis. Caused by Epstein-Barr virus. AB - The usual leukocyte response in infectious mononucleosis (IM) has been established in adults but not in children. Previously, the diagnosis of IM often was difficult in childhood due to the lack of detectable heterophil antibody response in many patients. Using Epstein-Barr virus-specific serology, we have documented IM in 45 patients between 1 and 15 years of age. the mean and ranges for the total leukocytes, percent lymphocytes, and percent atypical lymphocytes are presented. These do not vary significantly with age and are similar to those reported for adolescents and adults with this illness. PMID- 6267934 TI - Viral infections in pediatric burn patients. AB - Bacterial and fungal infections are frequent complications of burns, but the frequency of viral infections has not been defined. In a retrospective survey of serum for viral antibodies in pediatric burn patients, 22% had fourfold increases in antibodies to cytomegalovirus (CMV); 8% had increases to herpes simplex virus and to Epstein-Barr virus; and 5% had increases to varicella-zoster virus. None of the patients had evidence of adenovirus or hepatitis B virus infection. On the basis of these observations, a prospective study of viral infections, using both serologic and viral culture techniques, was performed. This study showed that in 33% of the children CMV infection developed; in 25%, herpes simplex infection; and in 17%, adenovirus infection. In all of the most severely burned children CMV infections developed, and both primary and reactivation infections were observed. Unexplained fevers are common in pediatric burn patients, and this study shows that some of these may be due to CMV infection. PMID- 6267935 TI - Serum angiotensin-converting-enzyme in Crohn's disease. AB - The serum angiotensin-converting-enzyme levels in patients with Crohn's disease have been determined. There is no significant difference in the serum levels of angiotensin-converting-enzyme in patients with active Crohn's disease, inactive Crohn's disease or Crohn's disease with demonstrated granuloma and normal controls. Patients with active Crohn's disease who are no steroid treatment do have significantly lower levels. PMID- 6267936 TI - Granular cell myoblastoma of the esophagus. Report of two cases. AB - Granular cell myoblastoma (GCM) of the esophagus is a rare, usually benign tumor, most often discovered incidentally during upper endoscopy, surgery, or autopsy. Although some reports have questioned the safety of endoscopic biopsy of granular cell tumors of the esophagus, we feel that the procedure can be performed safely and accurately. For the unwary, histological examination may lead to a misdiagnosis of squamous cell carcinoma. Although some reports of malignant esophageal tumors can be found, in general, if the histologic appearance of the tumor is benign, malignant transformation or metastasis is unusual. Surgical resection for malignant and for large symptomatic benign tumors is the treatment of choice. In, however, individuals with histologically benign tumors. who are asymptomatic or who are not considered good surgical candidates, careful observation with endoscopic follow-up can be safely done. PMID- 6267937 TI - Granular cell tumor of the esophagus. Report of three cases. AB - Granular cell tumors, (formerly called myoblastomas) involving the esophagus were encountered in three patients. In all three the tumors were asymptomatic and in two they were multiple. The first published endoscopic photographs of such a tumor are presented. The successful total removal of this neoplasm using the endoscope is described. The pathologic, radiologic and therapeutic aspects of previously reported cases of granular cell tumor of the esophagus are reviewed and compared with the three reported herein. PMID- 6267938 TI - pH dependency of potassium efflux from sickled red cells. AB - Potassium efflux from deoxygenated, hemoglobin S-containing red cells is often used as an "objective" in vitro measure of aed cell sickling, particularly during tests with antisickling agents. Since varying pH is known to affect both the extent of sickling and passive K+-flux across the red cell membrane, in opposite directions, we measured the sickling-related K+-efflux in sickle cell anemia (SS) and sickle cell trait (AS) red cells as a function of extracellular and intracellular pH. The sickling-related K+-efflux was found to show the same direction of pH dependence as normal red cells, so that as the extracellular pH was reduced below 7.6, sickling and K+-efflux were increasingly dissociated. A similar dissociation was observed between sickling and K+-efflux when the intracellular pH was lowered by increasing red cell organic phosphate levels. The sickling-related K+-efflux from osmotically shrunken AS cells (whose sickling tendency resembles that of SS cells) was similar in magnitude and pH dependency to that of the SS cells. The findings suggest that measurement of K+-efflux may be an accurate estimate of the extent of intracellular polymerization in sickled red cells, provided that both the intracellular and extracellular pH levels are carefully controlled, and the experimental conditions produce no independent effects on K+ permeability. PMID- 6267939 TI - A case of lead intoxication: clinical and biochemical studies. AB - A 23-year-old Japanese male with severe lead intoxication accompanied by hemolytic anemia was studied. The patient had taken 12 g to lead in about a month. He had moderate hemolytic anemia (Hb 8.9 g/100 ml) with reticulocytosis ranging from 2.5 to 11.7%. Peripheral blood smear showed nucleated red cells (42/200 white blood cells) and marked basophilic stippling in the red cells. Activities of erythrocyte enzymes were either normal or increased except for pyrimidine 5'-nucleotidase (P5N) and delta-aminolevulinic acid dehydratase (ALA D) both of which were found to be decreased, being 48.8% and 4.1% of the normal controls respectively. Erythrocyte reduced glutathione (GSH) was high (145.6 mg/100 ml RBC). Erythrocyte pyrimidine nucleotides were accumulated up to 10.2% of total nucleotides. The level of lead in peripheral blood was 112 microgram per 100 ml blood. Ca2+-Na2-EDTA was given to the patient as treatment. The level of lead in the blood decreased gradually and hemolytic anemia improved. Basophilic stippling in the red cells disappeared. These results confirmed the findings of Valentine et al [1] that lead-induced deficiency of P5N resulted in basophilic stippling and hemolytic anemia just like hereditary hemolytic anemia due to P5N deficiency. PMID- 6267940 TI - Antibody responses to varicella-zoster virus and the role of antibody in host defense. AB - Antibody titers to varicella-zoster (VZ) virus in persons aged 1-85 years were measured. Through age 50, the percent of seropostitive individuals continued to rise. There was no fall in geometric mean titer with aging, and there may have been an increase in VZ antibody titer in older persons. Thus, a fall in VZ antibody with increasing age does not seem likely to account for the increased incidence of zoster in the elderly. Similarly, immunocompromised patients who are more likely to develop zoster than normals did not have lower VZ antibody titers than normal persons. Finally, immunocompromised persons with disseminated zoster had antibody titers that were somewhat higher that those of immunocompromised persons with localized zoster. It appears that humoral immunity has little or no influence on either the development or the course of herpes zoster. PMID- 6267941 TI - Immunoperoxidase localization of papillomavirus antigens in cervical dysplasia and vulvar condylomas. AB - Biopsies of 50 cases of cervical dysplasia (46 mild and 4 moderate) and 40 cases of vulvar condyloma acuminata (genital warts) were screened for the presence of papillomavirus antigens by means of a peroxidase-antiperoxidase method having immunospecificity against the genus-specific (common) antigen(s) of the papillomaviruses. With the use of this technique, on formalin-fixed, paraffin embedded tissue, papillomavirus antigens were detected in cells with cytologic and histologic features of wart virus infection (so-called koilocytotic atypia). Cells showing a positive reaction for papillomavirus antigens were identified in 24 of 50 (48%) cases of cervical dysplasia and in 20 of 40 (50%) cases of vulvar condyloma. The results of this study provide specific confirmation of the presence of papillomavirus antigens in cervical dysplasia and suggest that the papillomavirus may be an important factor in the etiology of this disease. PMID- 6267942 TI - Current status of therapeutic modalities for treatment of gynecologic malignancies with emphasis on chemotherapy. PMID- 6267943 TI - Dental microwear and diet: implications for determining the feeding behaviors of extinct primates, with a comment on the dietary pattern of Sivapithecus. PMID- 6267944 TI - Nuclear progestin receptor-like component in human cervical tissue. AB - To study progestin action in human glandular cervix, we extracted the nuclear pellet with 0.5 M KCl and immediately adsorbed a progestin-binding receptor-like component to hydroxylapatite. Binding of 2 nM [3H]R5020 at 4 degrees C for 18 h, in the presence or absence of 100-fold molar excess progesterone and other steroids, was used to measure the total extractable and adsorbed progestin binding component. With this assay, the amounts of progestin-binding component in the nuclear-rich fraction in specimens from women in the follicular and luteal phases of the ovarian cycle were 930 +/- 143 and 995 +/- 148 fmol/g wet wt (+/- SE), respectively; total cytoplasmic progestin receptor was 2,989 +/- 812 and 1,861 +/- 188 fmol/g wet wt (+/- SE) in the follicular and luteal phases, respectively. The progestin-binding component extracted from the nuclear pellet has a sedimentation velocity coefficient in the 3.5 S region when measured in high salt on 5-20% linear sucrose density gradients that contain 10% glycerol. The progestin binding measured by the hydroxylapatite-exchange assay with [3H]R5020 and radio-insert progesterone is high affinity (Kd 2.6 X 10(-10) M) and heat labile and appears specific for progestins and progesterone target tissues. PMID- 6267945 TI - Epithelial organization and hormone sensitivity of toad urinary bladder cells in culture. AB - Two continuous cell lines (TB-M and TB-6c) derived from epithelial cells of the toad urinary bladder form epithelia in culture that manifest hormone-sensitive transepithelial transport. Development of transepithelial electrical resistance (R) and transport rate (ISC) are dependent on time and density of cells seeded, but steady-state ISC and R are characteristic for each cell line and independent of seeding density. Some responses of intact toad bladder are preserved in culture, whereas others are altered or absent. Neither cell line responds to vasopressin. Analogues of cAMP increase sodium transport and urea permeability in both cell lines but do not affect water permeability. The intramembrane particle aggregates associated with the vasopressin- and cAMP-induced increase in water permeability of the intact bladder could not be detected in the cell lines. Aldosterone increases sodium transport in both cell lines, and the time course and concentration dependence of the response to aldosterone are similar to those of the intact bladder. The relative effect of a series of steroids on ISC reveals corticosterone to be a more potent mineralocorticoid in cultured cells than in the intact bladder. PMID- 6267946 TI - Hormonal regulation of calcium transport in thick ascending limb renal tubules. AB - Net calcium efflux (JCanet) was compared in isolated perfused cortical and medullary segments of the thick ascending limb of Henle of the rabbit kidney. In response to the addition of calcitonin to the bathing medium, cortical segments showed no change in JCanet, whereas in medullary segments JCanet increased significantly. Similar studies substituting 8-bromo-cyclic AMP (8-BrcAMP) in concentrations of 10(-4) M or lower in the bath showed no effect on JCanet in either segment. When the concentration of 8-BrcAMP in the bath was increased to 10(-3) M, JCanet rose significantly in both segments. These results indicate heterogeneity of response to calcitonin in the cortical and medullary segments of the thick ascending limb of Henle, but a similar response of calcium transport to cAMP. Because we have previously shown that parathyroid hormone stimulates net calcium efflux in the cortical but not in the medullary segments of the thick ascending limb of Henle, the present observations suggest that cAMP may be the mediator of the actions of both calcitonin and parathyroid hormone. PMID- 6267947 TI - Regulation of renal Na+-K+-ATPase in the rat by adrenal steroids. AB - The effects of single and multiple injections of aldosterone and dexamethasone on renal Na+-K+-ATPase, in vitro renal gluconeogenesis, and urinary electrolyte excretion were examined in adrenalectomized rats in a dose-dependent manner. Single maximal and supramaximal doses of aldosterone (defined by the effect of electrolyte excretion) had no effect on Na+-K+-ATPase or gluconeogenesis. By contrast, a single administration of dexamethasone (in a dose range that increased fasting blood sugar, stimulated renal gluconeogenesis, and had no mineralocorticoid effects) yielded clear-cut activation of Na+-K+-ATPase. Multiple submaximal doses of dexamethasone produced quantitatively similar stimulation of Na+-K+-ATPase and gluconeogenesis. Multiple supramaximal doses of aldosterone stimulated Na+-K+-ATPase and gluconeogenesis, but maximal and submaximal doses of the hormone were without effect. Aldosterone had no effect on hepatic Na+-K+-ATPase or gluconeogenesis. These results suggest that activation of renal Na+-K+-ATPase can be considered a putative glucocorticoid (not mineralocorticoid) effect. Renal Na+-K+-ATPase activation by chronic aldosterone treatment may be mediated by glucocorticoid receptor sites and, hence, may not represent a genuine mineralocorticoid effect. PMID- 6267948 TI - Isoproterenol-induced restoration of contraction in K+-depolarized hearts: relationship to cAMP. AB - The action of isoproterenol on inotropic state, cAMP concentration, and phosphorylase b-to-a conversion was studied under conditions that are known to alter membrane properties in guinea pig papillary muscles. In accord with the results of other investigators, contractile events induced by electrical stimulation were abolished by tetrodotoxin (10 microM) or 22 mM K+ and were subsequently restored by the addition of isoproterenol (10 nM-100 microM). However, in the presence of 22 mM K+, but not tetrodotoxin, the dose-response and temporal relationships between isoproterenol and elevations in cAMP concentration were shifted to the right, whereas those for phosphorylase activation were shifted to the left. Thus the low concentrations (less than 10 nM) of isoproterenol that restored tension development did not produce a measurable increase in cAMP. Contractile responses induced by 10 nM isoproterenol were blocked by (--)-propranolol but not by (+)-propranolol or phentolamine. Methoxamine did not restore contractile events in 22 mM K+-treated muscles or induce changes in cAMP content or phosphorylase activation. These results show that conditions can be obtained (e.g., partial depolarization of cardiac cell membranes) in which beta-adrenergic receptor activation leads to restoration of inotropic state in guinea pig myocardium without an obligatory increase in tissue cAMP content. The restoration of contractile events and enhancement of phosphorylase response under these conditions suggest that beta-adrenergic receptor activation may lead to Ca2+-channel activation directly or by increasing a small pool of cAMP and thereby altering localized protein phosphorylation in the cell membrane. PMID- 6267949 TI - Psychiatric aftercare: identified needs versus referral patterns. AB - Although psychiatric aftercare has received increased attention, little is known about patients' needs for community resources or about predischarge referral patterns. The authors interviewed hospital staff about needs and referrals for each of 747 patients about to be discharged. Nearly all patients had needs in the medical/therapeutic area and most received referrals. In three other nonmedical aftercare areas needs were identified for a much lower percentage of patients, and identified need was two to three times greater than referrals made. The authors discuss the implications of these findings for the provision of aftercare services. PMID- 6267950 TI - Occurrence of enteroviruses in community swimming pools. AB - Municipal swimming pools and wading pools were examined for the presence of human enteric viruses using a portable virus concentrator at the site to concentrate viruses from 100-gallon to 500-gallon samples. Ten of 14 samples contained viruses; three of these were positive for virus in the presence of residual free chlorine. Enteroviruses were isolated from two pools which exceeded the 0.4 ppm free residual chlorine standard. This study appears to be supportive of recent evidence that indicates a higher incidence of enterovirus infection among bathers. All seven wading pool samples contained virus. Coxsackieviruses B3 and B4, poliovirus 1, and echovirus 7 were isolated. Total coliform bacteria were not adequate indicators of the presence of virus, as six of the samples were positive for virus but negative for coliforms. Total plate counts appeared to provide a better indication of the sanitary quality of the pool water, but viruses could still be detected in samples that met currently recommended bacterial levels. It is possible that swimming and wading pools may serve as a means of transmission of enteroviral disease, especially in children, during summer months. PMID- 6267951 TI - Glandular inclusions in lymph nodes. The problem of extensive involvement and relationship to salpingitis. AB - Para-aortic and pelvic lymph nodes surgically removed from 50 female patients were examined for glandular inclusions. The findings were correlated with fallopian tube changes in patients whose lymph nodes were found to contain inclusions. Seven of the 50 patients had lymph node glandular inclusions; in six, the inclusions were located primarily in the cortical or capsular regions and were few in number. Of these six patients, four had acute or chronic salpingitis. The seventh patient had exuberant lymph node glandular inclusions initially interpreted as metastatic adenocarcinoma and salpingitis isthmica nodosa. This patient is discussed in detail. The association of lymph node glandular inclusions with salpingitis has been reported twice previously; one of these two patients had salpingitis isthmica nodosa. These findings suggest a definite relationship between tubal disease lymph node glandular inclusions. The rare exuberant form of glandular inclusions is benign and should not be confused with adenocarcinoma. It appears definitely associated with salpingitis isthmica nodosa. We suggest two different mechanisms for the pathogenesis of these inclusions. The first is "benign metastasis" from the proliferating tubal epithelium to the draining lymph nodes. The second is a proliferative stimulus responsible for salpingitis isthmica nodosa which also acts on preexisting glandular inclusions to produce the extensive nodal lesion. PMID- 6267952 TI - Malignant fibrous histiocytoma of the larynx. AB - Malignant fibrous histiocytoma is a rare neoplasm composed of fibroblasts and histiocytes. It assumes several histologic forms, which account for its various names and the difficulty in its diagnosis and classification. A case thought to be the sixth malignant fibrous histiocytoma involving the larynx is presented. The treatment of choice is wide excision with close follow-up examination. PMID- 6267953 TI - Determination of mixtures of benzo[a]pyrene, 2,6-dimethylnaphthalene and their metabolites by high-performance liquid chromatography with fluorescence detection. PMID- 6267955 TI - Quantitative determination of conjugated and esterified estrogens by gas chromatography/chemical ionization mass spectrometry. PMID- 6267954 TI - Analysis of endo-beta-N-acetylglucosaminidase activity by high-pressure liquid chromatography on a silica-based chemically bonded octadecyl column. PMID- 6267956 TI - Seminal plasma biochemistry II: seminal plasma and spermatozoal cytidine monophosphate-sialic acid synthetase and sialyltransferase activities. AB - The zona pellucida receptor for spermatozoa has not been identified and the mechanism by which spermatozoa traverse the zona pellucida has not been elucidated. It is proposed that the zona pellucida receptor is a glycoprotein and the receptor per se is galactosamine or N-acetyl galactosamine. The mechanism by which spermatozoa transverse the zona pellucida may be by its structural modification, by the transfer of spermatozoal sialic acid. In addition, male infertility resulting from oligozoospermia or polyzoospermia, may be due to lack of spermatozoal bound sialyltransferase. A total of 43 semen samples were examined for cytidine monophosphate-sialic acid synthetase and sialyltransferase activities. It was found that both these enzymes are present in seminal plasma and bound to the spermatozoa. The spermatozoal bound enzymes may be derived from the seminal plasma which may be a limiting factor in terms of infertility. PMID- 6267957 TI - Slow channel inhibitors, anesthetics, and cardiovascular function. PMID- 6267958 TI - Succinylcholine neuromuscular blockade in subjects heterozygous for abnormal plasma cholinesterase. AB - The relationship between plasma cholinesterase genotype and duration and type of succinylcholine neuromuscular blockade was studied in 43 anesthetized patients heterozygous for abnormal plasma cholinesterase using train-of-four nerve stimulation. Twenty-eight patients were heterozygous for the usual and the atypical gene (E1uE1a), eight were heterozygous for the usual and the silent gene (E1uE1s), three were heterozygous for the usual and the fluoride-resistant gene (E1uE1f), three were heterozygous for the fluoride-resistant and the atypical gene (E1fE1a), and one was heterozygous for the fluoride-resistant and the silent gene (E1fE1s). Mean time to 90 per cent recovery of twitch height in patients with genotypes E1uE1a, E1uE1s, and E1uE1f (14.6, 12.4, and 12.0 min, respectively) was significantly prolonged compared to patients with normal cholinesterase genotype (9.3 min). No significant difference was found between the three groups of patients with one abnormal gene (E1uE1a, E1uE1s, and E1uE1f). In 13 (46 per cent) of the 28 patients with genotype E1uE1a the twitch height did not return to control for more than 15 min after the administration of succinylcholine and in three patients (10.7 per cent) for more than 20 min after succinylcholine. The four patients with abnormal genes on both chromosomes (E1fE1a and E1fE1s) all showed significantly prolonged paralysis following the administration of succinylcholine (mean time to 90 per cent twitch recovery was 30 min). Patients heterozygous for the usual and one of the abnormal genes (E1uE1a, E1uE1s, and E1uE1f) had typically depolarizing blocks following the administration of succinylcholine, 1 mg/kg. Patients with abnormal genes on both chromosomes (E1fE1a and E1fE1s), however, all showed desensitization type of neuromuscular blockade (phase II block). PMID- 6267959 TI - Infection studies in kittens, using feline infectious peritonitis virus propagated in cell culture. AB - The propagation of feline infectious peritonitis virus (NW1-FIPV strain) in cell culture is described. Tissue culture-propagated virus was used to inoculate specific-pathogen-free kittens intraperitoneally, intratracheally, or orally. Intraperitoneal inoculation caused seroconversion and effusive peritonitis in 100% of the kittens. Intratracheal inoculation produced disease in 60% of the kittens, and oral inoculation in only 20%. Seroconversions without production of disease occurred in 10% of the kittens inoculated by either the intratracheal or the oral route. The remainder of the kittens inoculated by the intratracheal (30%) and oral (70%) routes did not develop serum antibodies or disease. PMID- 6267960 TI - An enteric coronavirus infection of cats and its relationship to feline infectious peritonitis. AB - An enteric coronavirus that is antigenically closely related to feline infectious peritonitis virus (FIPV) is ubiquitous in the cat population. This virus has been designated feline enteric coronavirus to differentiate it from FIPV. The virus is shed in the feces by many seropositive cats; in catteries it is a cause of inapparent to mildly severe enteritis in kittens 6 to 12 weeks of age. The virus may produce a more severe enteritis in young specific-pathogen-free kittens. Feline enteric coronavirus selectively infects the apical columnar epithelium of the intestinal villi, from the caudal part of the duodenum to the cecum. In severe infections, there are sloughing of the tips of the villi and villous atrophy. Many cats recovering from the disease remain carriers of the virus. Recovered cats, observed for 3 to 24 months, remained healthy and did not develop peritonitis, pleuritis, or granulomatous disease. The relationship of feline enteric coronavirus and FIPV was studied. Although the viruses were antigenically similar, they were distinctly different in their pathogenicities. The enteric coronavirus did not cause feline infectious peritonitis in coronavirus antibody negative cats inoculated orally or intraperitoneally nor in coronavirus antibody positive cats inoculated intraperitoneally or intratracheally. Serologic tests, using FIPV, canine coronavirus, and transmissible gastroenteritis virus of swine as substrate antigens in fluorescent antibody procedures may not accurately identify FIPV infection. These tests do not appear to distinguish between FIPV and this feline enteric coronavirus. PMID- 6267961 TI - Pathogenesis of feline infectious peritonitis: nature and development of viremia. PMID- 6267962 TI - In vitro properties of low- and high-passaged strains of transmissible gastroenteritis coronavirus of swine. PMID- 6267964 TI - Turkey respiratory tract adenoviruses: oncogenic potential in neonatal hamsters (Mesocricetus auratus). AB - The tumorigenic properties of 3 turkey adenoviruses (CUA, NC-K, and MST) isolated from turkeys with respiratory tract disease and injected into neonatal hamsters (Mesocricetus auratus) have been determined. One of 30 adenovirus isolates (CUA) induced tumors at the site of inoculation (subcutaneously or intracranially) in neonatal hamsters. The tumors were identified as fibrosarcomas and undifferentiated sarcomas. The tumors were found to be free of infective virus, but hamsters which had tumors produced antibody to the virus-specific tumor antigen detectable by the complement-fixation test. The antibody titers for the tumor antigen were from 1:8 to 1:16. Abnormalities were not observed in the major organs collected from hamsters inoculated with the virus. Inoculations of hamster embryo cells and of adult and baby hamster kidney cells with the 3 turkey adenoviruses at a high multiplicity of infection did not produce transformed cells in monolayers. Hamster cells were permissive for CUA virus, since cytopathic effect was observed in 3 to 5 days after inoculation. PMID- 6267963 TI - Fractionation of Marek's disease virus-induced lymphoma by velocity sedimentation and association of infectivity with cellular fractions with and without tumor antigen expression. AB - Cell suspensions of lymphomas induced by Marek's disease (MD) virus were fractionated by sedimentation at unit gravity on a continuous gradient of bovine fetal serum. Cells in various fractions were examined for MD tumor-associated surface antigen (MATSA) by indirect immunofluorescence, using specific antibody, and for viral infectivity by cocultivating fractionated cells with permissive monolayer cells of duck embryo fibroblasts. Most MATSA-bearing cells in the lymphomas sedimented at a sedimentation velocity of greater than 3.0 mm/hour, whereas smaller, slow-sedimentating cells were generally devoid of MATSA expression. Viral infectivity was associated with MATSA-bearing and MATSA-lacking fractions. Within the limits of the experimental procedures used, this observation provided evidence that presence of MD virus genome in lymphocytes doses not result in concurrent expression of detectable MATSA and that MATSA likely represents another stage of interaction between MD virus and certain lymphocytes. PMID- 6267965 TI - Turkey respiratory tract adenoviruses: purification and some biochemical properties. PMID- 6267966 TI - Turkey respiratory tract adenoviruses: in vitro infectivity of purified DNA. PMID- 6267967 TI - Distribution of antibodies to rotavirus in serum and lacteal secretions of naturally infected swine and their suckling pigs. AB - Rotavirus antibodies were demonstrated in lacteal secretions and sera of 20 parturient sows and in sera of their newborn by an enzyme-linked immunosorbent assay blocking technique, using bovine rotavirus cell culture antigen and monospecific antibody to bovine rotavirus. Antibodies to rotavirus occur in the 3 immunoglobulin (Ig) classes IgM, IgA, and IgG in lacteal secretions. High and long-persisting antibody activity was mainly associated with the IgA class. The IgM and IgG decreased to undetectable concentrations in most sows during the 14 day investigation period. Serum antibodies of newborn pigs nursing their dams also decreased rapidly during this time. The heterologous enzyme-linked immunosorbent assay blocking technique was a reliable and rapid procedure for the demonstration of rotavirus antibodies. PMID- 6267968 TI - Recrudescence of infectious bovine rhinotracheitis virus and associated neural changes in calves treated with dexamethasone. AB - Reactivation of infection bovine rhinotracheitis (IBR) virus in calves administered dexamethasone (DM) was studied in 2 experiments. At 2, 3, 5, 15, or 30 months after inoculation of the Los Angeles strain of IBR virus, IV injections of DM were given for 5 consecutive days to induce a recurrent infection (experiment 1). Three months after the 1st treatment, a 2nd recurrent infection was induced, using DM with the same doses as used in experiment 1. The virus was excreted from nasal secretions from the 4th to the 10th day after initial treatment with DM, and from the 6th to the 9th day after the 2nd treatment. On pathologic examination, trigeminal ganglionitis, consisting of many proliferated microglia and inflammatory cells, was observed in all DM-treated calves. Moreover, degeneration of the ganglion cells and neuronophagia were prominent features in the calves after the 2nd recurrent infection. These observations indicated that the trigeminal ganglion may be one of the latent sites of IBR virus in calves after intranasal infection and that calves can develop a recrudescent infection after DM treatment several times during their lifetime. PMID- 6267969 TI - Epizootic hemorrhagic disease virus in Montana: isolation and serologic survey. AB - Epizootic hemorrhagic disease virus (EHDV) was isolated in Vero cell culture from the spleen and whole blood of a white-tailed deer (Odocoileus virginianus). A 10% spleen suspension caused acute hemorrhagic disease (HD) when inoculated into an experimental white-tailed deer and resulted in the recovery of EHDV from the blood of the experimental animal at 5 days after inoculation. The virus was identified as EHDV serotype 2 through indirect fluorescent antibody tests, electron microscopy, and reciprocal cross-neutralization tests. Approximately 73% (36/49) of the mule deer, 5% (2/42) of the white-tailed deer, and 79% (249/314) of the cattle samples tested from areas where HD had been reported were EHDV seropositive. Although none of the white-tailed deer was bluetongue virus seropositive, 29% of the mule deer and 3% of the cattle tested from "active" HD areas possessed bluetongue virus precipitating antibody. PMID- 6267970 TI - Pathologic features of horses given avirulent equine arteritis virus intramuscularly. AB - Twenty horses that were seronegative for equine arteritis virus antibodies were inoculated IM with live equine arteritis virus vaccine. The inoculation did not cause clinical signs of disease. A mild, transient febrile reaction developed in 6 horses, 3 of which were in poor condition before inoculation. Six horses, 2 of which were in poor condition before inoculation, experienced mild lymphopenia. Necropsy revealed mild lesions in the lymph nodes of 6 horses (3 of which were in poor condition before inoculation). Maximum concentrations of virus were detected in the lymph nodes and were consistently present from postvaccination day 3 through 8. Lesser concentrations of virus were detected in the spleen of 5 horses, liver and kidney of 4, abdominal fluid of 3, pleural fluid of 2, and lungs and urine of 1, between postvaccination days 3 and 7. Virus was not detected in the brain, nasal tract, or serum of any of the horses. PMID- 6267971 TI - Chrysotile asbestos inhalation in rats: deposition pattern and reaction of alveolar epithelium and pulmonary macrophages. AB - The initial deposition and subsequent translocation of chrysotile asbestos were studied in the lungs of rats exposed for 1 h in inhalation chambers. Using scanning and transmission electron microscopy of tissue fixed by vascular perfusion, we determined that the majority of fibers that pass through the conducting airways deposits at the bifurcations of alveolar ducts. The farther an alveolar duct bifurcation was from its terminal bronchiole, the less asbestos were observed. The amount of asbestos present on the alveolar duct surfaces was significantly decreased 5 h after cessation of the 1-h exposure. Some fibers were taken up by Type I epithelial cells during the first hour of dusting, and this process continued through the 8-day period in which the animals were studied. As early as 24 h after exposure, there was an accumulation of macrophages at the sites of initial asbestos deposition. This may be a significant cellular response in the early pathogenesis of asbestosis. PMID- 6267972 TI - [Threshold for bicarbonate in epileptic children in treatment with anticonvulsant drugs (author's transl)]. AB - The study comprised 31 ambulatory epileptic children aged 1,5-14 years (mean: 7.37), receiving treatment with anticonvulsant drugs. Authors found that renal threshold for bicarbonate was inferior when compared to control group (mean = 21.3 mEq/l., SD = 1.75; mean = 25.34 mEq/l., SD = 1.29; p less than 0.0001), low calcemia (mean = 9.12 mg./dl., SD = 0.51; mean = 9.43, SD = 0.45; p less than 0.01) and elevated alkaline phosphatase (mean = 212.6 mU/ml., SD = 75.9; mean = 127.4, SD = 50.2; p less than 0.01). No significant difference in urinary excretion of cyclic AMP, phosphate or calcium was observed. Nineteen patients who had subnormal threshold (inferior to -2 SD in the control group) when compared with control group, had: low calcemia (p less than 0.01), high alkaline phosphatase (p less than 0.0001) and a similar urinary cyclic AMP, calciuria and phosphaturia. A negative correlation between renal threshold to bicarbonate and serum phosphate (r = -0.49, p less than 0.01) and a negative correlation between the urinary cyclic AMP and the duration of treatment (r = -0.42, p less than 0.05) was found. It is commented that although in deficiency rickets, proximal tubular acidosis is due to secondary hyperparathyroidism, in their patients despite they had biochemical characteristics of rickets, low calcemia and elevated alkaline phosphatase, the descent of renal threshold to bicarbonate is a nonparathoromone mediated phenomenon. PMID- 6267973 TI - [Kidney and osseous responsiveness to PTH in a case of pseudohypoparathyroidism (author's transl)]. AB - A case of pseudohypoparathyroidism is described, finding in addition to the typical clinical data described in the literature an all almost total atrophy of the minor lips and clitoris, a perforated hymen and a "paradoxical" increase of convulsions with anticomicial treatment. Study of response of urinary phosphates and AMPc to PTH, was negative (Drezner type I). Osseous response to PTH was negative (Frame type I pseudohypoparathyroidism). Pathogenic possibilities are discussed. PMID- 6267974 TI - [Wilms' tumor and acute post-traumatic intratumor hemorrhage]. PMID- 6267976 TI - Nonenzymic control of prothrombin activation. PMID- 6267975 TI - Myeloperoxidase deficiency: prevalence and clinical significance. AB - Leukocyte differential counting by flow cytochemistry has shown 28 subjects with partial or complete neutrophil myeloperoxidase (MPO) deficiency in a population of about 60 000 patients screened at a general hospital. Partial (13 patients) or complete (13 patients) MPO deficiency was confirmed by examination of cytochemical stains in 26, biochemical measurement of total enzymatic activity in eight, and flow cytometry in six patients. None had apparent hematologic disorders. Only four patients had infections; of these, two had major systemic infections (one, candidiasis; one, bacteremia). In assays of leukocyte function only minor defects in killing of Staphylococcus aureus by MPO-deficient cells were noted whereas killing of Candida albicans was much more impaired. Family studies in eight patients have shown various degrees of partial or complete MPO deficiency in first-degree relatives of six. The findings indicate that the incidence of MPO deficiency is much higher than previously suspected. Although MPO appears to be necessary for killing of Candida species by neutrophils, the importance of its role in normal antibacterial defense must be re-evaluated. PMID- 6267977 TI - A sensitive, coupled assay for plasminogen activator using a thiol ester substrate for plasmin. PMID- 6267978 TI - Preparation of radioactive antithrombin and studies of its reaction with thrombin. PMID- 6267979 TI - Diagnosis of tumors of the kidney: ultrastructural classification. AB - Diagnosis of tumors of the kidney depends principally on clinical evaluation and radiologic studies. The role of the pathologist is most important in the classification and characterization of the tumors. In addition, morphologic studies employing the use of electron microscopy may aid in the understanding of histogenesis and the recognition of tumor sub-types. Electron microscopic evaluation indicates specific cellular features characteristic of renal adenocarcinoma, nephroblastoma, and sarcomas. Ultrastructural examination can be particularly useful in distinguishing between sarcomas and sarcomatoid carcinomas and in identifying the origin of metastatic tumors. For these reasons, the use of electron microscopy for the evaluation of renal tumors is recommended in selected cases. PMID- 6267980 TI - Acquired lesions in transplanted kidneys. AB - A retrospective study of acquired renal lesions in 42 renal transplants in children revealed a variety of histologic lesions. Although acute and chronic rejection changes were the most frequent, a number of metabolic, infectious, vascular, and other lesions were encountered. Renal biopsy allows rapid diagnosis of these lesions, permitting rational planning for therapy. PMID- 6267981 TI - Polyneuropathy with monoclonal gammopathy: studies of 11 patients. AB - Among patients with chronic idiopathic nonfamilial polyneuropathy studied 3 to 21 years after onset, we identified 11 cases associated with monoclonal gammopathy (MCG) (5 with IgGk, 4 with IgMk, 2 with IgG lambda). The patients, aged 29 to 80 years, presented with sensorimotor polyneuropathy of insidious onset and slow, nonfluctuating progression, delayed motor and sensory nerve conduction, and increased cerebrospinal fluid (CSF) protein. None of the patients in the initial or follow-up study (mean, 9.2 years) had or developed signs of multiple myeloma, malignant plasma cell dyscrasia, macroglobulinemia syndrome, amyloidosis, neoplasia, or other associated illness. The CSF revealed abnormalities of protein electrophoresis or immunoelectrophoresis in 9 of the 11 patients. Three of 5 sural nerve biopsies studied by immunofluorescence demonstrated deposition in nerve fibers of the light chain characteristic of the abnormal circulating immunoglobulin. The findings suggest that these patients form a distinct subset of the dysimmune neuropathies. Although the immunoglobulin deposition and abnormal protein patterns in serum and CSF could be secondary to nerve damage, we propose that an immunopathological mechanism underlies the neuropathy. Immunosuppressants had minimal to marked beneficial effect in 4 of 5 patients, indicating that this polyneuropathy is potentially treatable. PMID- 6267982 TI - CSF changes during acute meningoencephalitis in mice caused by encephalomyocarditis virus. AB - Encephalomyelitis was induced in mice by intravenous inoculation with encephalomyocarditis virus. Examination of the cerebrospinal fluid revealed marked pleocytosis and increased amounts of protein, including immunoglobulins. These proteins entered the cerebrospinal fluid by transfer from serum during the period of central nervous system infection. PMID- 6267983 TI - Parainfectious acute obstructive hydrocephalus. PMID- 6267984 TI - Autologous lymphocyte proliferation in multiple sclerosis and the effect of intravenous ACTH. AB - The proliferative response of peripheral blood T cells to autologous non-T cells, a reaction called the autologous mixed lymphocyte reaction (MLR), was significantly increased in 17 patients with active multiple sclerosis (MS) compared to age- and sex-matched individuals with other neurological diseases (OND). Following a 10-day course of intravenous adrenocorticotropic hormone (ACTH) therapy the values were reduced to control levels. No differences were noted between MS patients and controls in their response to alloantigens. The increased autologous MLR in patients with active MS appeared to result from an increased stimulatory capacity of non-T cells rather than from an intrinsically greater T cell proliferative potential. ACTH appeared to induce a change in the populations of circulating non-T cells such that these cells had a decreased stimulatory capacity in both autologous and allogeneic MLR. The decrease in stimulatory capacity in autologous MLR was, however, significantly greater than the decrease in allogeneic stimulatory capacity, suggesting a functional decrease of specific non-T cell-enriched subpopulations. No significant changes in the numbers of myeloperoxidase-positive (MP+) cells were noted in the blood of MS patients before and after ACTH therapy. Since the autologous MLR results in generation of cells that regulate immune responsiveness, the changes noted provide additional evidence for abnormal immune regulation in MS. PMID- 6267985 TI - Progressive neurological disease associated with chronic cytomegalovirus infection. AB - Cytomegalovirus (CMV), the most common infectious cause of nervous system damage in the fetus and newborn infant, generally has been thought to exert its teratogenic effect during early pregnancy, and it has been assumed that clinical or postmortem abnormalities reflect static insults incurred earlier. Over the past two years we have identified two infants who presented with various clinical signs suggesting CMV infection. Serial CT head scans showed mild hydrocephalus progressing to extensive loss of brain substance and hydrocephalus in one and a normal scan going on to polycystic encephalomalacia in the other. Both infants had urine or leukocyte cultures that were repeatedly positive for CMV. These data suggest that CMV can cause progressive central nervous system damage after birth. The findings may account for some unexplained brain malformations and for a portion of the neurodegenerative disorders occurring in babies who appear normal at birth. PMID- 6267986 TI - Transmembrane transport of cobalamin in prokaryotic and eukaryotic cells. PMID- 6267987 TI - Proteins controlling the helical structure of DNA. PMID- 6267988 TI - Structure and mechanism of multifunctional restriction endonucleases. PMID- 6267989 TI - Glycoprotein hormones: structure and function. PMID- 6267990 TI - Proton-translocating cytochrome complexes. PMID- 6267991 TI - Molecular approaches to the study of fertilization. PMID- 6267992 TI - Biochemistry of diseases of immunodevelopment. PMID- 6267993 TI - DNA topoisomerases. PMID- 6267994 TI - [Frequency of the incorporation of the ampicillin-resistance transposon Tn 1 into the lactose operon found on the bacterial chromosome at the F' factor]. PMID- 6267995 TI - [Role of sterols in the interaction of polyene antibiotics with lipid membranes]. AB - The problem whether the membrane sterols are indirect acceptors of polyenic antibiotics or they play the role of substances providing conditions (at the expense of putting in order the membrane phospholipids) for formation of conductive complexes (ionic canals) from the antibiotic molecules is discussed. The comparative study on the ability of sterols of various structure (ergosterol, 7-dehydrocholesterol, cholesterol, 5 alpha-cholestan-3 beta-ol) to interact with the membrane phospholipids and to increase the sensitivity of such membranes to amphotericin B showed no correlation between the levels of these properties. The value of the changes in the cross elasticity module (E) of artificial bilayer lipid membranes from egg lecithin on introduction of the above sterols into their composition was used as the criterion for the interaction level. The absence of correlation between the above properties of the sterols indicated that the role of the sterols in interaction of polyenic antibiotics with the membranes could not be considered as the only effect of the sterols on putting in order the phospholipids, which confirmed the hypothesis on the acceptor function of the sterols with respect to polyenic antibiotics. The study of the effect of amphotericin B on the elastic properties of the cholesterol-containing bilayer membranes isolated from egg lecithin showed tha the values of the longitudinal and cross elasticity modules of the membranes did not change during introduction into the membranes of the ionic canals. PMID- 6267997 TI - Gynecomastia with ketoconazole. AB - Three of forty men developed bilateral gynecomastia upon ketoconazole treatment. Symptoms abated despite continued therapy. This appears to be a direct drug effect on breast tissue. PMID- 6267996 TI - [Comparative study of the antiviral activity of pancreatic and microbial RNAse]. AB - The efficacy of pancreatic RNase with microbial enzymes (RN-ases) of Act. rimosus and Bacillus intermedius) was studied comparatively in vitro in a transplantable cell culture of the swine embryokidney with respect to the aphthosa virus (AV) and the virus of the Aujeszky disease (VAD). The VAD proved to be most sensitive to RNases. RNase of Bac. intermedius showed the highest antiviral efficacy. The enzymes were active in vivo, when the albino mice and newborn rabbits were infected with the AV, the RNase of Bac. intermedius being also most active in this case. PMID- 6267998 TI - [Angiotensin-converting enzyme (ACE). Increased serum activities in patients with dermatological diseases (author's transl)]. AB - Serum activities of ACE were investigated in 40 patients with dermatological disease and in nine patients with sarcoidosis. The method of Cushman and Cheung, modified according to Lieberman, was used. Both sarcoidosis patients and patients with dermatological diseases showed marked elevations of ACE-activity. The increase in ACE-activity might result from inflammation and immunological events. PMID- 6267999 TI - [Effects of prostaglandins (PGE1) on the development of amebas i experimentally infected rats]. PMID- 6268000 TI - [Experimental amebiasis: effect of PGE1 on rats infested with Entamoeba histolytica]. AB - The authors have studied the effects of PGE1 on rats (Wistar strain) infected with Entamoeba histolytica, and inoculated with PGE1 either in massive dosage and killed after 3-5 and 7 days, or with daily minimum quantity of PGE1 and killed on days 7 and 15 after inoculation. The results show an inhibition effect of PGE1 on development and survival of amoebae in the coecum of rats inoculated with the two modalities described above. The fractionated dosage gives better results and less side effects. PMID- 6268001 TI - [Virological studies in respiratory diseases observed in Sassari between November 1978 and March 1979]. PMID- 6268002 TI - Differential distribution of cyclic-AMP receptors in human spermatozoa. AB - The binding properties of cyclic-AMP to intact and fractionated in heads and tails human spermatozoa have been studied. Whole spermatozoa bound 6.8 +/- 0.8 pmol of cyclic-AMP per 10(7) cells. Binding of cyclic-AMP was selectively located in the midpiece-tail region of the spermatozoa. Thus only 18% of the binding in the whole sperm could be accounted for by the binding on the sperm heads. This distribution is similar to that previously described for the protein kinase of bovine sperm. Blocking membrane sulfhydryl groups with pCMBS induced a drastic inhibition (65%) of the cyclic-AMP binding to the sperm heads, while only moderately reducing (30%) the binding in the sperm tails PMID- 6268003 TI - Histochemistry of some steroid-dehydrogenases in epithelia of human seminal vesicle, deferential ampulla, and prostate gland. AB - The cytochemical localization of 17 beta-SDH, 3 beta-SDH, and 3 alpha-SDH was made in human seminal vesicle, deferential ampulla and prostate. The enzymes showed a remarkable activity in the epithelial cells of all glands. The epithelia of prostate, seminal vesicle, and deferential ampulla were able to metabolize androgens through the reductive pathway, characteristic of target tissues. PMID- 6268004 TI - Hypotensive effect of labetalol on intraocular pressure in rabbits: in relation to its alpha- and beta-adrenergic blocking action on the cardiovascular system. AB - Rabbits anesthetized with urethane were used. Labetalol was found to be about 3.7 times less potent than phentolamine in blocking phenylephrine-induced vasopressor response, and about 7.6 times less potent than propranolol in blocking isoproterenol-induced vasodepressor response. Labetalol (0.3, 1.0 and 2.5 mg/kg, i.v.) decreased both intraocular pressure (IOP) and mean arterial blood pressure (BP) significantly, and also decreased IOP/BP ratio. Propranolol (1.0 and 2.5 mg/kg, i.v.) reduced both IOP and BP slightly without affecting the IOP/BP ratio. Phentolamine (1.0 mg/kg, i.v.) reduced both IOP and BP significantly, but it did not alter the IOP/BP ratio. When both propranolol (1.0 mg/kg, i.v.) and phentolamine (1.0 mg/kg, i.v.) were injected at the same time, IOP and BP were reduced with a decrease in IOP/BP ratio. These findings suggest that labetalol is effective in decreasing the IOP, although the mechanism of the drug action cannot be explained simply by alpha- and beta-adrenergic blockade. PMID- 6268005 TI - Oxytocin-induced Ca-free contraction of rat uterine smooth muscle: effects of divalent cations and drugs. AB - When rat myometrium that had been depleted of Ca by incubation with 3 mM EGTA for 50 min was challenged with 10(-2) unit/ml oxytocin, it showed sustained contraction in a medium with no added Ca (Ca-free contraction). It also showed Ca free contraction of similar magnitude in the presence of 1 mM EGTA. The effects on this contraction of divalent cations (Co2+, Ni2+ and Mn2+) singly and in combination with D-600 (3 X 10(-6) M) were investigated. Co2+ and Ni2+ potentiated Ca-free contraction concentration-dependently, and their effects were greater in the presence of D-600. In contrast, Mn2+ evoked a triphasic response; first transient potentiation, second relaxation, and third persistent increase in tension. D-600 did not block the first or second, but blocked the third, resulting in persistence of the second phase of relaxation. The relaxing action of papaverine on Ca-free contraction was not affected by D-600. Isoproterenol and dibutyryl cyclic AMP also relaxed the contraction. PMID- 6268006 TI - The influence of dopamine and dopaminergic agonists on the contractions of field stimulated rat vas deferens. AB - In isolated field stimulated rat vas deferens frequency-response curves were shifted to the right by noradrenaline, dopamine, apomorphine, bromocriptine and nomifensine. Piribedil was found to be inactive. Phentolamine antagonized the effect of each active drug. The inhibition due to dopamine and apomorphine was also counteracted by haloperidol and sulpiride, while that caused by bromocriptine and nomifensine only by sulpiride. On the basis of these results an interaction was suggested between the presynaptic alpha and dopaminergic receptors: in the rat vas deferens dopaminergic receptors might activate alpha 2 receptors. The agonists increased the slope of the frequency-response curves. The drugs had a reversible activity on the vas deferens, except for bromocriptine which could not be removed by repeated wash-outs from the organ. PMID- 6268007 TI - Calcium ions and the influence of chagasic sera on the effects of ouabain on isolated rat atria. AB - The effects of chagasic sera containing an antibody (EVI antibody) on "non toxic" and "toxic" actions of ouabain on isolated rat atria suspended in different media, were explored. Ouabain failed to evoke any significantly positive contractile effect on atria beating in EVI Positive Human Sera (EVI(+)S), and only produced "toxic" actions (arrhythmias, contracture enhanced frequency, reduced inotropism). On the contrary, atria beating in Krebs-Ringer-Bicarbonate (KRB) or in Normal Human Sera (NHS) reacted to added ouabain with a classical dose-dependent positive inotropic effect. The threshold concentration of ouabain required to elicit the onset of "toxic" effects was higher in KRB than in EVI(+)S. Decreasing the extracellular Ca2+ concentration or treating the auricles with verapamil, facilitated positive inotropic influence of ouabain and attenuated the "toxic" effects observed on atria beating in EVI(+)S. In addition, the combination of (--)-propranolol plus verapamil enhanced the facilitatory influence of verapamil induced on the positive inotropic effect of ouabain and reduced the "toxic" influences evoked on atria exposed to EVI(+)S. These findings support the notion that the overall "toxic" responses to ouabain on cardiac tissue immersed in an EVI(+)S containing solution may be related to a combined effect of the EVI antibody activating beta-adrenoceptors as well as to a rise in the tissue Ca2+ content. PMID- 6268009 TI - Effects of dopamine and its antagonist domperidone cannot be explained by an effect on alpha 1-adrenergic receptors. PMID- 6268008 TI - The influence of sodium gamma-hydroxybutyrate on GABA receptors and catecholamine effect potentiation. AB - The effects of microiontophoretically applied gamma-hydroxybutyric acid and gamma hydroxybutyrate (GHBA-Na) on the extracellularly registered spontaneous neuronal electrical activity of rabbit's sensorimotor and frontal cerebral cortex were studied. GHBA-Na depressed the firing of cortical neurons in a dose-dependent manner. This effect was blocked by bicuculline. It was concluded that GHBA-Na interacted with GABA receptors of the neuronal membrane. During traumatic epilepsy GHBA-Na caused excitation of cortical neurons and showed antagonistic relationships with GABA. It is supposed that during epilepsy GHBA-Na binds with GABA receptors, decreases competitively the effect of natural GABA and thus it might cause a disinhibition of neurons. GHBA-Na increased and prolongated the depression of the neurons of frontal cortex which was caused by microiontophoretical application of catecholamines: dopamine and norepinephrine. It is suggested that GHBA-Na prevents catecholamines inactivation. PMID- 6268010 TI - [Ultrastructure of adenoid-cystic carcinoma as a sign of malignity (comparison of ultramicroscopical investigations concerning adenoid-cystic carcinoma and adeno carcinoma of salivary glands) (author's transl)]. AB - The ultrastructure of Adenoid-cystic carcinoma of salivary glands analysed by 7 cases is compared with ultrastructure of Adenocarcinoma. Both carcinomas have corresponding secretory cells. The dysregulation of secret production is typical in Adenoid-cystic carcinoma and Adenocarcinoma and based on defective differentiation and missing innervation of carcinoma cells. The diversity of tumour-cells, increased by nesecretory cells, based on large cytogenetic prospection of acinary and ductulary epithelium of salivary glands. Based on the ultramicroscopical correspondence of secretory cell-types in both carcinomas the malignity of the Adenoid-cystic carcinoma is founded. PMID- 6268011 TI - Breast cancer and TRH -- response. AB - The study was made in an effort to determine the thyroid function of breast cancer patients. Plasma TBC levels, plasma TSH basal levels and the TSH levels after stimulating with TRH were evaluated in 37 postmenopausal cancer patients and 30 age matched controls. Neither TBC and TSH basal levels nor stimulated TSH levels were significantly different between the controls and the various stages of cancer patients. Thus, the study cannot confirm other reports suggesting a possible role of thyroid in the development of breast cancer. PMID- 6268012 TI - Fatal Epstein-Barr virus infection in a 63-year-old man. An autopsy report. AB - A 63-year-old man with acute, heterophil-negative Epstein-Barr (EBV) viral infection displayed neurologic impairment that progressed to coma and death. Fever, pharyngitis, and lymphadenopathy were notably absent. There was no lymphocytosis, and multiple peripheral smears revealed few atypical lymphocytes. Results of specific EBV serology were diagnostic of acute infection. At the time of autopsy, there was massive intravascular and perivascular infiltration of all organs by lymphocytes and atypical mononuclear cells. There was depletion of the paracortical T-lymphocyte areas of lymph nodes. The atypical mononuclear cells did not contain intracytoplasmic immunoglobulin, as shown by the immunoperoxidase technique, nor did they take up esterase stains, but their electron-microscopic features were characteristic of lymphoid cells. These morphologic findings suggest a T-cell defect, with unrestricted proliferation of B lymphocytes. The lack of characteristic clinical and hematologic features in this case underscores the value of specific EBV serology in the diagnosis of acute heterophil-negative EBV infection. PMID- 6268013 TI - [Effect of native crude fiber on the digestibility of nitrogen and amino acids in pigs]. AB - In experiments with fattening pigs peas and lupines were used, both pealed and unpealed, in order to investigate the influence of native crude fibres on the true digestibility of nitrogen and the amino acids in pigs. The results of the experiments allow the conclusion that native crude fibres, as long as they remain in the normal range between 3 and 7% in the ration does not cause a depression in the true digestibility of nitrogen and the amino acids in the feeding of fattening pigs. Only the increased content of native crude fibres in the ration has a negative effect on true digestibility. PMID- 6268014 TI - The presence of intranuclear lipid inclusions in hepatocytes of mice after chronic ingestion of polybrominated biphenyl. AB - Electron microscopic study of livers from mice fed 167 ppm polybrominated biphenyl (PBB) for 12 weeks showed hepatocytes with nuclei containing varied amounts of lipid inclusions. The inclusions appeared as spherical vacuoles free in the nuclear matrix. This is the first report of the induction of lipid inclusions within the nucleus by a halogenated hydrocarbon. PMID- 6268016 TI - 2,3-Dimercaptosuccinic acid in human arsenic poisoning. PMID- 6268017 TI - Detection of HBsAg in a clone derived from the PLC/PRF/5 human hepatoma cell line. AB - A total of 28 clones were established from the PLC/PRF/5 hepatoma cell line by a plating procedure. All clones were found to secrete HBsAg into the supernatant culture fluids. Of these, one clone (No. 23) free of detectable mycoplasma contamination and showing smooth epithelial morphology was selected for further study. Maximum accumulation of HBsAg occurred 9 days after sub-culture and intracellular antigen was detected by indirect immunofluorescence both in the cytoplasm and at the plasma membrane. Granules and perinuclear staining reactions were also observed in clone 23 cells and these findings are compared to the previously published properties of the parental PLC/PRF/5 cell line. PMID- 6268015 TI - Effect of the bispyridinium compounds HGG12, HGG42, and obidoxime on synaptic transmission and NAD(P)H-fluorescence in the superior cervical ganglion of the rat in vitro. AB - Postganglionic compound action potential (AP) and intracellular NAD(P)H fluorescence were recorded simultaneously in the perifused superior cervical ganglion of the rat (SCG) to study the effects of the bispyridinium oximes HGG12, HGG42 and obidoxime. HGG12 and HGG42 inhibit the compound action potential (AP) (ID50: 70 microM) and the reductive part of NAD(P)H changes (ID50: 75 microM) recorded upon stimulation of the SCG, while obidoxime has no ganglion blocking effects in concentrations up to 1 mM. The effects of inhibitors of cholinergic transmission were also studied in order to understand the mechanisms of action of the oximes. Hexamethonium (C6) and atropine, competitive inhibitors of receptors of nicotinic and muscarinic cholinergic transmission respectively, were found to block synaptic transmission (C6 ID50:150 microM, atropine ID50: 70 microM) and the reductive part of the NAD(P)H response (C6 ID50: 70 microM, atropine ID50: 50 microM) in a quantitatively similar way. Comparison of the ganglionic action of HGG12 and HGG42 with that of the inhibitory agents characterises them as inhibitors of receptors of nicotinic ganglionic transmission. Furthermore at concentrations of about 10 microM, HGG12 behaves like atropine and leads to an increase in AP and reductive fluorescence response. It is therefore probable that HGG12 has in addition an affinity for ganglionic muscarinic receptors which HGG42 does not have. PMID- 6268018 TI - Biochemical characterization of simian foamy virus type i. AB - Simian syncitium-forming ("foamy") virus type I (SFV1) was characterized biochemically. RNA was extracted from purified virus either with 0.1 per cent SDS or by the standard phenol-chloroform method. By both techniques a main component of 65-70S was found. Denaturation of the 65-70S RNA by heat resulted in a shift of the sedimentation coefficient mainly to a 30-35S component. Electrophoresis on a composite polyacrylamide gel demonstrated the existence of three minor RNA's: 8S, 5S and 4S respectively. PAGE-SDS analysis of disrupted purified virions enabled the separate migration of five viral proteins and the identification of two main proteins: a 30 kd polypeptide and a 70 kd polypeptide. PMID- 6268020 TI - Some biological and physico-chemical properties of egg drop syndrome (EDS) avian adenovirus strain B8/78. AB - The EDS adenovirus produced either in the allantoic cavity of embryonated duck eggs (A0 virus) or in chicken embryo liver cell cultures (TC0 virus) were comparatively studied by gradient ultracentrifugation in CsCl. The A0 viral particles banded at densities of 1.36 and 1.31 g/ml, whereas, the TC0 viral particle were found at densities of 1.33 and 1.31 g/ml, respectively. The heavy populations contained infectious and hemagglutinating particles if they were not pelleted and sonicated before gradient ultracentrifugation. Pelleting or sonicating the viral particles resulted in loss of hemagglutinating activity of the heavy populations. The light particles were hemagglutinating but not infectious regardless of the previous treatment. The pH- and heat-sensitivity of the B8/78 virus strain was similar to those described for CEL0 (FAV-1) adenovirus (5). The B8/78 virus strain replicated well in tissue cultures of chicken and goose origin causing the formation of intranuclear inclusion bodies in the infected cells. PMID- 6268019 TI - Inhibitory effects of foscarnet on herpesvirus multiplication in cell culture. AB - The effect of phosphonoformate (INN; foscarnet sodium) on Herpes Simplex Virus type 1 replication in cell-culture has been studied. At 55 microM, foscarnet reduced the yield by 50 per cent which correlated well with a 50 per cent reduction of plaque formation at 60 microM. Foscarnet had to be added before 8 hours post infection to inhibit virus production. The inhibition of herpesvirus plaque formation by the presence of foscarnet for 24 hours was not reversed by the removal of the drug. The inhibition of virus replication by foscarnet could, in contrast to the inhibition by acycloguanosine, not be reversed by addition of deoxynucleosides. PMID- 6268021 TI - Variables that may influence the alkaline sedimentation pattern of herpes simplex virus DNA. AB - Herpes simplex virus (HSV) DNA sediments homogeneously on a neutral sucrose gradient but heterogeneously on an alkaline sucrose gradient. Several factors that may influence the alkaline sedimentation pattern of HSV DNA were examined: e.g., the host cell, cell density at time of infection, multiplicity of infection, and the starting material for HSV DNA purification (whether HSV infected cells or cell-free virus). Based on alkaline sedimentation analysis, these factors appear to play little or no role in the amount of intact single stranded HSV DNA observed. PMID- 6268022 TI - Virion polypeptide heterogeneity among virulent and avirulent strains of eastern equine encephalitis (EEE) virus. AB - Comparative analysis of structural virion polypeptides of 24 selected EEE virus strains, representing North and South American types, was performed by one dimensional discontinuous sodium dodecyl sulfate (SDS)-polyacrylamide-gel electrophoresis (PAGE). The structural proteins of different EEE virus isolates, resolved by this method, exhibited mol.wts. values in the range of 57-60 X 10(3) for (E-1), 51-54 X 10(3) for (E-2) and 35-38 X 10(3) daltons for the core (NP) nucleocapsid. The exception was the South American human lethal virus, TRVL-89287 strain, which was shown to possess only a single envelope glycoprotein. The high molecular weight envelope (E-1) glycoprotein species was absent or co-migrated adjacent to the smaller envelope (E-2) glycoprotein. Results indicated similarities in the core (NP) proteins, however greater variability in the envelope (E-/ and/or E-2) glycoproteins. Based on these variations seven distinct profiles could be observed among the EEE virus strain studied. The classification based on the patterns of structural polypeptides obtained by SDS-PAGE of these strains does not correlate well with any other previously reported in vitro characteristics (antigenic subtypes, HTP elution profiles) nor with the in vivo virulence markers. PMID- 6268024 TI - The detection and behaviour of the herpesvirus of malignant catarrhal fever in bovine lymphocytes. PMID- 6268025 TI - The relationship among silica, silicosis, and lung carcinoma. PMID- 6268023 TI - Dissociation between cellular DNA- and histone synthesis following infection by cytomegalovirus in the presence of phosphonoacetic acid. PMID- 6268026 TI - [Ultrastructural characteristics of seminoma and embryonal cancer of the testis]. AB - Twenty-three germ cell tumors of the testis were investigated. Electron microscopic examinations of four seminomas and four embryonal carcinomas revealed cells of different degrees of differentiation. Tumor cells of seminoma acquired the ultrastructural features of the cells of developing seminal epithelium whereas in embryonal carcinoma there was a pronounced tendency of formation of mature tissues of teratoma. These data confirmed the cytogenetic resemblance of seminoma and embryonal carcinoma originating from the seminal epithelium which could undergo malignization at different stages of development. The latter predetermined diverse direction of differentiation in germ cell tumors of the testis. PMID- 6268027 TI - [Method of detecting alkaline phosphatase and 5-nucleotidase in histological bone sections]. AB - Modification of the methods of Gomory, Pearce, and Reis for the detection of alkaline phosphatase and 5-nucleotidase in the bone tissue is described. The authors used fixation of the bone tissue in acetone at a temperature of 0 to 4 degrees C for 6 to 12 hours, decalcification in Grip's fluid followed by cutting in a freezing microtome of incompletely decalcified bone material and its decalcification in sections. As a result, localization of the enzyme is detected by the distribution of black sediments of cobalt sulfide. PMID- 6268028 TI - [Cyto- and histological comparisons in chemodectomas of the neck]. AB - Cyto-histological correlations in cases of chemodectomas of the neck were made. The patients were divided into 3 groups; with benign (8), malignized (8) and malignant (14 tumors). Decreased vascular component, solidization, marked cellular and nuclear polymorphism taken together are signs of morphological malignizaiton of the tumor. In most patients, however, no relationship between morphological characteristics of chemodectomas and their clinical course was established. Clinico-morphological correlations indicate that cellular and tissue changes are not the only signs of malignancy of a tumor. PMID- 6268030 TI - Characterization of a microsomal fraction from rabbit parotid gland partial separation of alkaline phosphatase from Na+,K+-ATPase. PMID- 6268029 TI - [Primary malignant liver tumors in children]. AB - The review is based on the analysis of 17 national and 58 foreign publications dealing with the epidemiology, classification, age features, morphology, ultrastructure, histogenesis, complications and outcomes of primary malignant tumors of the liver in children. This analysis showed primary tumors of the liver in children to occupy the third place among neoplasia of the abdominal cavity and retroperitoneal space. There are no universally accepted terms for their designation and this prevents the development of a unique classification. Under 3 years, tumors develop predominantly from the embryonal tissue: hepatoblastomas of epithelial and mixed types frequently combined with congenital disorders and malformations of other organs. At more advanced age, hepatic carcinoma, a tumor of the adult type, is found. The review deals with the problems of histogenesis and classification of primary hepatic tumors in children. An opinion is given on the entodermo-mesodermal nature of embryonal hepatic tumors from the pluripotential blastema capable of malignization both into entodermal and mesodermal components. The prognosis of the disease is poor, 90% of children with hepatoblastoma and 80% with hepatocarcinoma die within one year after the diagnosis is established., PMID- 6268031 TI - Immunohistochemical localization and distribution of cyclic nucleotides in the rat mandibular condyle in response to an induced occlusal change. PMID- 6268033 TI - Alcohol addiction: are the endogenous opioids involved? PMID- 6268034 TI - The lumbar spinal canal in hypophosphataemic vitamin D-resistant rickets. AB - Lumbar spine radiographs of 17 adult patients with hypophosphataemic vitamin D resistant rickets have been examined and measured in their anteroposterior and transverse dimensions. Comparison of these measurements with those of a group of normal individuals showed the HPR patient group to have narrower spinal canals in both diameters. No differences were found between males and females in either group. The lumbar spinal canal stenosis in adult HPR patients may make them more susceptible to spinal cord compromise from space occupying lesions within the canal, causing back pain and lower limb weakness for which surgical intervention may be indicated. PMID- 6268032 TI - Coronavirus-associated antibodies in nasopharyngeal carcinoma and infectious mononucleosis. AB - Coronavirus-like particles are found within the cytoplasm of NPC tumor cells, within the cytoplasm of the tumor cells of the regional metastases, and within tumor cells grown on nude mice. For the immunologic identification of the coronaviruses, the cultures of human tracheal epithelium (MRC-C) were used and inoculated with a known coronavirus strain. Whereas blood sera from NPC patients (n = 73) contain significantly elevated antibody titers against corona viruses, unselected sera from patients without NPC showed a low antibody titer (n = 83). Only patients suffering from infectious mononucleosis (n = 40) showed a titer pattern similar to that of NPC patients. For demonstration of antigen-antibody reaction within the NPC tumor cell cytoplasm, sera with a high antibody content against coronaviruses deriving from other than NPC patients or anticoronavirus sera from rabbits were used. By indirect immunofluorescence, the NPC tumor cells showed a bright cytoplasmic fluorescence. No fluorescence was seen when tumor cells were exposed to human sera with known low or absent corona antibody titer or to normal rabbit sera. The results indicate that next to a DNA virus infection (EBV), an RNA virus infection (coronavirus) may play a role in NPC as well as in infectious mononucleosis. PMID- 6268035 TI - The isolation of a probable pestivirus from a goat. PMID- 6268036 TI - The distribution of naturally acquired antibodies against infectious bursal disease virus in Victoria. PMID- 6268037 TI - Vaccination of pigeons against pigeon herpes encephalomyelitis virus. PMID- 6268038 TI - The detrimental effect of vaccinating parentally immune broilers with a modified liver virus vaccine for infectious bursal disease. AB - The experiment involved 392,955 broilers from breeders vaccinated with a commercially available killed infectious bursal disease (KIBD) virus vaccine (Treatments 1 and 2) and 373,371 broilers from breeders not vaccinated with a KIBD virus vaccine (Treatment 2). The broilers from the KIBD-vaccinated breeders were divided into two treatment groups: Treatment 1 consisted of 209,457 broilers and Treatment 2 consisted of 183,498 broilers. Treatment 2 broilers were vaccinated at 10 days of age intraocularly with a commercially available modified liver infectious bursal disease virus (IBD-MLV) vaccine. Broilers in all three treatments were raised on commercially contracted farms serviced by the same company representative. Broiler performance was based on mortality, body weight, feed efficiency, condemnations, and how each farm ranked with respect to contract settlements. Compared with birds in Treatments 2 and 3 respectively, Treatment 1 broilers had 1.65% and 0.89% less mortality; 0.22 lbs. and 0.09 lbs. increased weight per bird; 0.03 and 0.03 increased feed efficiency; 0.09% and 0.32% fewer air sacculitis condemnations; and 0.57% and 0.83% fewer total condemnations. Treatment 1 broilers ranked in the top 37%; Treatment 2 ranked in the bottom 36%; and Treatment 3 ranked in the lower 57% of contract settlements for all broilers processed. The results clearly showed that Treatment 1 broilers outperformed Treatment 2 amd 3 birds and that the IBD-MLV vaccine had a detrimental effect on Treatment 2 broilers. PMID- 6268040 TI - Pathogenicity of two strains of Mycoplasma gallisepticum in broilers. AB - Strains F and R of Mycoplasma gallisepticum (MG) were compared in two laboratory trials for their relative pathogenicity in terms of inducing airsacculitis and antibody production to MG. Chickens exposed to the R strain had significantly higher incidence of air-sac lesions (P less than 0.05) and greater severity of airsacculitis than did chicks exposed to the F strain. In both trials, chickens vaccinated simultaneously with Newcastle disease-infectious bronchitis vaccine and exposed to MG had more severe lesions than did chickens exposed to mycoplasma alone. chickens exposed to the F strain had significantly lower geometric mean hemagglutination-inhibition antibody titers to MG than did chicks exposed to the R strain. Chickens vaccinated simultaneously with Newcastle disease-infectious bronchitis vaccine and exposed to R strain had significantly lower body weights than did chickens in the other group. PMID- 6268039 TI - A survey of non-specific cross-protective immunities induced by avian retroviruses. AB - Reticuloendotheliosis virus strain T (REV-T) induced immunity in chicks to challenge by representative subgroup members of the avian leukosis-sarcoma virus (ALSV) complex. Immunity levels were compared to determine the extent of antigenic relation between REV-T and the ALSV complex. Reciprocal studies using ALSV subgroup members and pheasant viruses as immunogens and REV-T as challenge were also performed. It was concluded that reciprocity of immunity is not equal between the viruses studied, nor is immunity directly related to the virus neutralizing-antibody levels induced by immunization with the viruses studied. In some cases, the levels of cross-protection demonstrated may be a sign of the induction of antibodies to common or similar tumor-specific surface antigens rather than complete antigenic identity between REV-T and the ALSV members used; in others, virus-neutralizing antibodies may be a sign of partial identity between some proteins of REV-T and ALSV subgroup members. PMID- 6268041 TI - Neutralizing antibodies to CELO and avian adenovirus-associated viruses in the albumen of chicken eggs. AB - Neutralizing antibodies to CELO virus and to avian adenovirus-associated virus (A AV) were detected in the albumen of eggs from four hens inoculated with these viruses. The antibody concentrations of serum, yolk, and albumen were determined before inoculation and at various times postinoculation (PI) by enzyme-linked immunosorbent assay (ELISA) and virus-neutralization (VN) tests. The antibody concentration in albumen was 0.3% to 1.0% of that detected in serum and yolk. Uninoculated hens showed no detectable antibody in serum, yolk, or albumen. It is suggested that the presence of antibody in the egg albumen may play a role in egg transmission of viruses. PMID- 6268042 TI - Effects of infectious bursal disease on Marek's disease vaccination: suppression of antiviral immune response. AB - Studies were made to determine whether infectious bursal disease virus (IBDV) infection would affect the response of chickens to turkey herpesvirus (HVT) vaccination in the development and level of HVT viremia and virus-neutralizing (VN) antibodies to HVT. The HVT viremia in the vaccinated chickens was not affected by IBDV, whether IBDV was inoculated simultaneously with HVT vaccination at one day of age or whether it was inoculated 3 weeks postvaccination with HVT. However, VN antibody response to HVT was significantly suppressed (P less than 0.001) when vaccinated chickens were exposed to IBDV either at the time of vaccination or at 3 weeks postvaccination. Such immunosuppression by IBDV of VN antibody response to HVT vaccination may result in a reduced antiviral immunity against Marek's disease virus. PMID- 6268043 TI - Susceptibility of ducks to the virus of infectious laryngotracheitis. PMID- 6268044 TI - Conditions for successful cultivation of tumor cells from chickens with avian lymphoid leukosis. AB - To determine a suitable source of tumor cells that would readily adapt to in vitro growth, attempts were made to culture lymphoid tumor cells in soft agar from several neoplastic organs from chickens with lymphoid leukosis. Of 10 tumors from 7 chickens, cells from only two--both from enlarged bursae--were grown successfully. The remaining 8 tumors failed to propagate. The two cell lines thus established have been propagated by serial passage for more than two years in continuous culture. The two cell lines grow as single, free-floating cells in suspension. Morphologically they are usually round, about 8-10 microns in diameter, and have the characteristics of lymphoblastoid cells. They propagate to a maximum concentration of about 1-2 X 10(6)/ml and release infective virus of subgroup A to titers as high as 10(7) TCID/ml. Their leukosis/sarcoma virus susceptibility phenotype is C/E. Lymphoid tumors developed on chorioallantoic membranes (CAM) of 10-day-old embryonated eggs of the BK line 7 days after inoculation, whereas no tumors developed on CAMs from the 15I line. PMID- 6268045 TI - Pathogenicity for chickens of a reovirus isolated from turkeys. AB - A viral agent that was isolated from livers of commercial turkey poults that died at approximately two weeks of age was characterized as a reovirus. Experimental infection of day-old chickens with this reovirus isolate resulted in the development of tenosynovitis, hepatitis, and myocarditis. In vitro neutralization of the turkey reovirus isolate by antiserum against chicken reovirus correlated with in vivo protection of maternally immune chickens from day-old oral challenge with the turkey reovirus isolate. PMID- 6268046 TI - Serological identification of avian adenoviruses isolated from cases of inclusion body hepatitis in Victoria, Australia. AB - Sixteen avian adenoviruses isolated from 12 cases of inclusion body hepatitis (IBH), 3 cases of respiratory disease, and a case of ruptured tendons were compared using antisera raised against 9 fowl adenovirus prototype strains. Eleven isolates from livers of birds with IBH were classified into 4 different serological groups: 1) YR36 (type 7)-related; 2) HVI (type 8)-related; 3) Variants--type 6-,7-, and S-related; and 4) Type 50--not closely related to any of the prototype antisera tested. These results indicate that, as in other countries, IBH in Victoria is associated with several serologically distinct adenoviruses. The other five adenovirus isolates were found to be related to CELO (type 1). PMID- 6268047 TI - Immune profile of infectious bursal disease. III. Effect of infectious bursal disease virus on the lymphocyte responses to phytomitogens and on mixed lymphocyte reaction of chickens. AB - A whole-blood-culture technique was used to sequentially evaluated peripheral blood lymphocyte responses to phytohemagglutinin (PHA) and concanavalin A (Con A) of normal chickens and chickens infected at 1 day or 3 weeks of age with infectious bursal disease virus (IBDV). This method had numerous advantages over the more conventional techniques. A comparative study was made on the percentage of inhibition of responses of peripheral blood lymphocytes to PHA and Con A of 1 day- and 3-week-old IBDV-infected chickens. In both groups, there was a minimum inhibition between 3 and 4 weeks postinfection (PI) and a maximum inhibition at 6 weeks PI. A one-way mixed lymphocyte reaction (MLR) was performed using mitomycin C-treated cells as stimulator cells obtained from chickens of genetically different strains. Lymphocytes from the experimental birds (control, 1-day infected, and 3-week-infected groups) were used as the responder cells. The results showed that MLR response of the IBDV-infected chickens was significantly reduced compared with those of the uninfected controls. The degree of lowered response was much more severe in chickens infected at 1 day of age than in those infected at 3 weeks of age. PMID- 6268048 TI - Comparison of a tissue-culture virus-neutralization test and the enzyme-linked immunosorbent assay for measurement of antibodies t infectious bronchitis. AB - Two serological tests, the virus-neutralization (VN) test in tissue culture using a tissue-cell-adapted virus and the enzyme-linked immunosorbent assay (ELISA), were compared to detect antibodies against Massachusetts 41 and Connecticut 46 strains of Infectious Bronchitis Virus (IBV). The VN test was conducted in wells of microplates by the usual procedure. The two strains of IBV were adapted after 20 serial passages to induce CPE in 24 hours in chickens embryos kidney cells (CEKC). The ELISA test was carried out using partially virus following ultracentrifugation of each stain of IBV as antigen. The ELISA test detected higher geometric mean antibody titers (GMT) against both strains of IBV than did the VN test. One hundred four serum samples taken at 1, 3, 5, 9, 22, 24, and 26 weeks of age from a flock of chickens vaccinated with the Mass strain three times and the Conn strain of IBV two times during the growing period showed higher antibody titer responses to the Conn 46 than to the Mass 41 strain. Maternal antibodies in chicks one week of age were readily detected by the ELISA test, whereas low or insignificant titers were found by the VN test. Sera of vaccinated chickens collected following challenge with Mass 41 or Conn 46 strain of IBV showed that the ELISA was more sensitive and showed higher titers than did the VN test. Although the VN test showed no rise in GMT in the same sera tested with the heterologous virus, the ELISA showed a slight increase or cross-reaction. The serum samples from the unchallenged control group showed no change in GMT with either test or IBV strain. PMID- 6268049 TI - Humoral immune response of the duck to duck hepatitis virus: virus-neutralizing vs. virus-precipitating antibodies. AB - Ducks were induced to develop high-level duck hepatitis virus (DHV)-neutralizing antibodies by inculation with a chicken-embryo-adapted DHV via subcutaneous, intramuscular, and intratracheal routes. Administration of the DHV orally in a gelatin capsule failed to stimulate immune response in the ducks. Contact controls of these ducks also remained negative for anti-DHV antibodies. These observations indicated that the DHV administered orally, in gelatin capsule, failed to infect the ducks. None of numerous duck anti-DHV immune sera, with virus-neutralizing activity in the range of 1.8 to 5.57 log10 median- embryo infective-dose (EID50) neutralization index, developed precipitin lines against a variety of DHV preparations tested in low- and high-ionic-strength agar. The results suggest that the agar-gel immunodiffusion test is unsuitable for serologic testing of duck sera for anti-DHV antibody activity. Virus-neutralizing activity was revealed in both immunoglobulin M (IgM) and IgG classes of sera of actively immunized ducks. Immunodiffusion tests of Sephadex G-200 fractions of 1 day-old duckling sera with monospecific rabbit anti-duck IgM (DIgM) serum failed to detect DIgM. These results demonstrated that the IgM is not being transferred from the dam to the newly hatched ducklings. Seven- and 14-day-old ducks had DIgM in their sera. However, this IgM had no DHV-neutralizing activity, indicating that it was newly developed by the ducklings, which had no active DHV immune response, not having been exposed to DHV. PMID- 6268050 TI - An outbreak of duck virus enteritis (duck plague) in a captive flock of mixed waterfowl. PMID- 6268051 TI - Improved performance of progeny of broiler parent chickens vaccinated with infectious bursal disease oil-emulsion vaccine. AB - Field trials were conducted on nine broiler chicken flocks, which were the progeny of parents vaccinated with inactivated infectious bursal disease (IBD) oil-emulsion vaccine (OEV). The average increase in overall weight gains was 7.97% of weight gains of similar birds from live-vaccinated parents. Food conversion ratios (FCR) were calculated for five of the trials. The average improvement in FCR over that of the control chickens was 2.89%. Every broiler flock contracted subclinical IBD, but there was no significant difference in overall mortality rates, except in one trial. In that trial, inclusion body hepatitis and Escherichia coli septicemia in the progeny of the parents that received only live vaccines caused increased mortality. Weekly monitoring of IBD antibodies in two of the trials showed that, in one trial, maternally derived antibody (MDA) persisted in the test chicks until at least 22 days of age and in the controls until at least day 15. In the other trial, MDA persisted until at least day 15 and day 8, respectively, in the test and control flocks. Field IBD challenge occurred at about day 30 and day 37 in the control and test chicks, respectively, in one trial and on day 17 and day 30 in the other. Overall weight gains and FCRs were not related to stocking densities. PMID- 6268052 TI - Difference between influences of homologous and heterologous maternal antibodies on response to serotype-2 and serotype-3 Marek's disease vaccines. AB - Marek's disease (MD) vaccines representing serotypes 2 (SB-1 strain of MD virus) and 3 (FC-126 strain of turkey herpesvirus) were administered to 1-day-old MD susceptible chicks that either were free of antibodies or carried maternally derived antibodies against SB-1, FC-126, or a serotype-1 MD virus, CU-2 strain. Homologous antibodies delayed the development of vaccine virus viremias and inhibited vaccinal immunity, as judged by protection against challenge with the virulent JM-10 strain of MD virus 7 days postvaccination. Heterologous antibodies had little effect on vaccine responses. Antibodies were shown to interfere with both cell-associated and cell-free vaccine virus. PMID- 6268053 TI - Crystallinity of tissue mineral as evaluated by electron spin resonance spectometry. AB - Crystallinity of bone mineral as well as mineral deposited in the course of pathological calcification was measured by the use of electron spin resonance (esr) spectometry in tissue samples previously irradiated with ionizing radiation. Defects caused by irradiation in the crystalline lattice of hydroxypatite crystals are paramagnetic in nature, stable and connected with the crystalline fraction of tissue mineral only. The crystallinity coefficient, defined as the ratio of these paramagnetic centers to the total ash content, changes in bone in the course of development, ageing and in pathology. The accuracy and sensitivity of esr method developed for estimation of crystallinity of tissue mineral are discussed. Examples are given for application of the esr method for the research of normal and pathologically changed mineralizing tissues. The sensitivity of the esr method permitted the measurements of crystallinity of single isolated osteons in different stages of calcification, as well as the evaluation of crystallinity of mineral deposits in subcellular fractions, e.g., calcium-loaded mitochondria. The developed technique might be applied in clinical research for diagnosis and monitoring of therapy in selected bone diseases. PMID- 6268054 TI - cAMP and regulation of carbohydrate metabolism. PMID- 6268055 TI - Regulatory controls in relation to over-production of fungal cellulases. PMID- 6268056 TI - Possible role of prostaglandins in the regulation of coronary blood flow. AB - Prostaglandins may represent one group of local chemical factors that control coronary perfusion and adapt it to the metabolic demands of the heart. Present study summarizes the current knowledge in this field with particular reference to prostacyclin (PGI2). The major biosynthetic pathways and their modification by drugs are briefly outlined. The sources and fates of cardiac prostaglandins are described and possible mechanisms of action discussed in both physiological and pathophysiological (myocardial ischemia) situations. Attention is focussed on the interplay between catecholamines, adenosine and PGI2. A model is presented, based on the hypothesis that adenosine from myocardial metabolism and PGI2 from vascular sites are acting in concert to antagonize sympathetic metabolic and vasoconstrictory influences and to maintain an adequate blood supply to the heart. PMID- 6268058 TI - [Serological studies for the presence of hemagglutination-inhibiting antibodies against the "egg-drop syndrome 76" virus in South Wuerttemberg]. PMID- 6268059 TI - [Pharmacokinetics and toxicology of lithium]. AB - The pharmacokinetics of lithium is reviewed in regard to the pattern of lithium concentration in plasma, red blood cells, saliva and urine and to a four compartmental model of lithium distribution. An overview of lithium toxicology is given summarizing the gastrointestinal, cardiovascular, endocrine, hematological, dermatologic, teratogenic and neurological side effects of lithium. The results of two controlled studies are described in detail. The investigation of thyroid function in 88 patients under lithium treatment revealed abnormally high values of TSH and/or of TSH response to TRH in 50% of the subjects. By use of daily protocols of eating and drinking over a period of 14 days, a distinctly higher caloric intake (from solid food, not fluids) was found in 10 patients who gained weight during lithium therapy as compared to 10 lithium-treated patients without weight gain. PMID- 6268057 TI - Response of cyt a,a3 in the situ canine heart to transient ischemic episodes. AB - Experiments were performed to examine the response of cyt a,a3 to transient ischemic and hypoxic episodes in the empty, fibrillating canine heart in situ. Using a dual wavelength, differential spectrophotometer, reaction spectra show an absorption peak at approximately 605 nm consistent with that obtained from purified cyt a,a3. The characteristics of the averaged reaction spectrum in the interval 590 nm to 610 nm indicate that hemoglobin/myoglobin contribute no more than 23% to the signal measured at 605 nm. A regimen of one 30 sec global ischemia (GI) repeated once every 3 minutes over a 90 min period showed no appreciable signal deterioration. Therefore, five such interventions were subsequently used as the test perturbation. Studies of the effects of ischemic episodes of 30 and 60 min show that the response of cyt a,a3 to this test intervention was smaller (90 +/- 6% and 89 +/- 7%) than that observed prior to the ischemic episode. Changes in coronary perfusion pressure (+/- 10 Torr) produced an immediate oxidation/reduction of cyt a,a3. In the working heart, just prior to fibrillation, 6 sec to interrupted ventilation resulted in a continuous reduction of cyt a,a3. The data from these studies show: 1) The redox state of cyt a,a3 may be continuously monitored in the canine heart in situ. 2) Following ischemias of 30 and 60 min duration, respiratory chain function may be impaired; and 3) The well-perfused epicardium is extremely sensitive to small changes in oxygen delivery. PMID- 6268060 TI - Effects of endotoxin on the myocardial (Na+ + K+)-ATPase enzyme system: involvement of lipids in endotoxin-induced changes in enzyme activities. PMID- 6268061 TI - Jejunal cAMP-activated sodium secretion via deconjugated bile salts and fatty acids. PMID- 6268062 TI - A cAMP-binding protein from Dictyostelium discoideum regulates mammalian protein kinase. PMID- 6268063 TI - Effect of a methyl-transferase inhibitor, 5'-deoxy'5'-S-isobutyl-thioadenosine (SIBA) on cAMP level and progesterone induced meiosis reinitiation in Xenopus laevis oocytes. PMID- 6268065 TI - Evidence for the involvement of a rapidly turning over protease in the degradation of cytochrome oxidase in Neurospora crassa. PMID- 6268064 TI - Synthesis of hypomethylated Epstein-Barr viral DNA is stimulated by dimethylsulfoxide treatment of lymphoblastoid cells. PMID- 6268066 TI - Influence of bile acids on the soluble phosphatidic acid phosphates in rat liver. PMID- 6268067 TI - Direct binding studies do not support the existence of true alpha-adreno receptors in rat white fat cells. PMID- 6268068 TI - Herpes specific and alpha DNA polymerase in nuclear envelope of BHK infected cells. PMID- 6268069 TI - Stimulation of photophosphorylation by low concentrations of uncoupling amines. PMID- 6268070 TI - Glucose-dependent metabolic interconversion of fructose-1, 6-bisphosphatase in yeast. PMID- 6268071 TI - Inhibition of calmodulin-activated cyclic nucleotide phosphodiesterase by Triton X-100. PMID- 6268072 TI - Glucagon stimulation of fructose 1,6-bisphosphatase phosphorylation in rat hepatocytes. PMID- 6268073 TI - Preferential uncoupling by manganese of alpha adrenergic receptor mediated inhibition of adenylate cyclase in human platelets. PMID- 6268074 TI - Cobra venom cardiotoxins as probes of altered membrane structure in dystrophic skeletal muscle. PMID- 6268075 TI - A helix-destabilizing protein substrate devoid of heterocyclic bases. PMID- 6268076 TI - In vitro effect of prostaglandins on corticosterone and aldosterone production by frog interrenal gland. PMID- 6268077 TI - The 2'5' oligoadenylate synthetase has a multifunctional 2'5' nucleotidyl transferase activity. PMID- 6268078 TI - Control of fatty acid synthetase mRNA levels in rat liver by insulin, glucagon, and dibutyl cyclic AMP. PMID- 6268079 TI - Different sedimentation properties of agonist- and antagonist-labelled platelet alpha 2 adrenergic receptors. PMID- 6268080 TI - A cationic electron spin resonance probe used to analyze cation interactions with lipopolysaccharide. PMID- 6268081 TI - Effect of adrenocorticotrophic hormone on the activity of sterol ester hydrolase from rat brain. PMID- 6268082 TI - Comparison of lipophilic proteins in murine and avian oncornaviruses. PMID- 6268083 TI - An irreversible tissue inhibitor of collagenase in human amniotic fluid: characterization and separation from fibronectin. PMID- 6268084 TI - Changes in phospholipid metabolism of SV3T3 transformed fibroblasts restricted by plating and cultivation at low serum concentration and subsequently re-stimulated by serum. PMID- 6268085 TI - Reduced chemotactic peptide binding in juvenile periodontitis: a model for neutrophil function. PMID- 6268086 TI - Inhibition of human fibroblasts sphingomyelinase by cholesterol and 7 dehydrocholesterol. PMID- 6268087 TI - The fate of SV40 DNA in infected cells after treatment with benzo(a)pyrene diol epoxide. PMID- 6268088 TI - Extraction of mitochondrial protein-lipid complexes into organic solvents: inhibition of cytochrome oxidase electron transport by dicyclohexylcarbodiimide and triphenyltin chloride. PMID- 6268089 TI - Calmodulin and cyclic nucleotide phosphodiesterase activities in erythrocytes from normal and schizophrenic subjects. PMID- 6268090 TI - An extremely acidic copper-containing protein from chromaffin granules. PMID- 6268091 TI - The disparity between effects of vanadate (V) and vanadyl (IV) ions on (Na+-K+) ATPase and K+-phosphatase in skeletal muscle. PMID- 6268093 TI - Effects of d- and l-propranolol on the responsiveness of human fibroblasts to choleragen and prostaglandin E1. PMID- 6268094 TI - Effects of phenobarbital, 3-methylcholanthrene and beta-naphthoflavone pretreatment on mouse liver microsomal enzymes and on metabolite patterns of benzo[a]pyrene. PMID- 6268092 TI - Xenobiotic metabolism by alveolar type II cells isolated from rabbit lung. PMID- 6268095 TI - Properties of 8,9-dichloro-2,3,4,5-tetrahydro-1H-2-benzazepine, an inhibitor of norepinephrine N-methyltransferase. PMID- 6268096 TI - Influence of clonidine-like hypotensive drugs on adrenergic platelet reactions. PMID- 6268097 TI - Interaction of imipramine with the ionic channel of the acetylcholine receptor of motor endplate and electric organ. PMID- 6268098 TI - Properties and functions of calmodulin. PMID- 6268099 TI - Studies on the mechanism of toxicity of reduced lantadene A in rats. PMID- 6268100 TI - No evidence for reverse trans-synaptic regulation of neuronal uptake by beta adrenoceptors in kitten atria. PMID- 6268101 TI - Inotropic responses of the frog ventricle to dibutyryl cyclic AMP and 8-bromo cyclic GMP and related changes in endogenous cyclic nucleotide levels. PMID- 6268102 TI - In vivo spin-trapping of radicals formed during halothane metabolism. PMID- 6268103 TI - Interaction of depressant, convulsant, and anticonvulsant barbiturates with the [3H]diazepam binding site of the benzodiazepine-GABA-receptor-ionophore complex. PMID- 6268104 TI - Spectroscopic studies of rat mast cells, mouse mastocytoma cells, and compound 48/80--III. Evidence for a protein binding site for compound 48/80. PMID- 6268106 TI - Two distinct alpha1-adrenergic receptor sites in rat liver: differential binding of (--)-[3H]dihydroergocryptine. Effects of guanine nucleotides and proteolysis; implications for a two-site model of alpha-receptor regulation. PMID- 6268105 TI - A reaction of acetaldehyde with enkephalins and related peptides. PMID- 6268107 TI - Na+, K+-ATPase activity and noradrenaline turnover in brown adipose tissue of rats exhibiting diet-induced thermogenesis. PMID- 6268109 TI - An ubiquitous protein which regulates calcium-dependent cellular functions and calcium movements. PMID- 6268108 TI - Generation of semiquinone radical from carbazilquinone by NADPH-cytochrome P-450 reductase. PMID- 6268110 TI - The effect of intracerebroventricularly administered dibutyryl adenosine 3',5' cyclic monophosphate on cerebrospinal fluid and serum dopamine-beta-hydroxylase in rabbits. PMID- 6268111 TI - Inhibition of testosterone synthesis by ethanol and acetaldehyde. PMID- 6268113 TI - Multiple opiate receptors in peripheral tissue preparations. PMID- 6268112 TI - Dopamine receptor alterations with aging in mouse and rat corpus striatum. PMID- 6268114 TI - Effect of a prostaglandin antagonist, N-0164, on cAMP generation and hydrolysis in the rat uterus. PMID- 6268115 TI - Fluoride-induced superoxide production in rabbit polymorphonuclear leukocytes. PMID- 6268116 TI - Characterization and quantitation of alpha-adrenergic receptor subtypes in rat hypothalamus. PMID- 6268117 TI - Mechanism of inhibition of sodium- and potassium-dependent adenosine triphosphatase by the isoquinoline derivative BIIA: a specific interaction with sodium activation. PMID- 6268118 TI - Strontium ions induce production of thromboxane B2 and secretion of 5 hydroxytryptamine in washed human platelets. PMID- 6268119 TI - Concerning the determination of xanthine oxidase in biological material via its ability to produce superoxide. PMID- 6268120 TI - Benzoxazolone-5-sulphonanilides, 1-(benzoxazolone-5'-sulphonyl)-benzotriazoles and 4-hydroxy-3,2'-diaminobenzenesulphonanilides with antiviral activity. AB - benzoxazolone-5-(2'-nitro)-sulphonanilides were synthesized by acylation of o nitroanilines with benzoxazolone-5-sulphochloride or 3-methylbenzoxazolone-5 sulphochloride. The nitro group in these compounds was subjected to reduction and the resulting amino derivatives were cyclysed to yield the corresponding 1 (benzoxazolone-5'-sulphonyl)-benzotriazoles. Decyclization of the oxazolone cycle of benzoxazolone-5-(2'-amino)-sulphonanilides resulted in 4-hydroxy-3,2' diaminobenzenesulphonanilides. In vitro testing of the antiviral activity of the compounds obtained during successive synthetic steps revealed that some of them exhibited marked antiviral effect against toga, orthomixo, oncorna and herpes viruses. PMID- 6268121 TI - [The effect of pentoxifylline on the Ca2+-induced potassium efflux and on the ATPase-activity of erythrocytes (author's transl)]. AB - The efflux of K+ from aged human erythrocytes is regulated by Ca2+: 5--100 mumol/l Ca2+ stimulate and 1--5 mmol/l Ca2+ inhibit K+-efflux. In fresh erythrocytes Ca2+ is virtually without effect on transport of K+. 3,7-Dimethyl-1 (5-oxohexyl)-xanthine (pentoxifylline) (5.5 mmol/l) decreases the K+-efflux from fresh erythrocytes by 10%. Similar effect of pentoxifylline is observed on the Ca2+-induced K+-efflux from aged erythrocytes. The ATPase-activity of a human erythrocyte membrane is stimulated in in vitro experiments by 1--100 mumol/l Ca2+. Increased concentration of Ca2+ (1--5 mmol/l), inhibits ATPase-activity. Pentoxifylline (0.5 mmol/l) modulates the effect of Ca2+ (conc. 1 mmol/l) on ATPase. It can be suggested that the rheological effect of pentoxifylline (possibly chelated with Ca2+) is caused by the decrease of Ca2+-caused K+-efflux and by the regulation of ATPase-activity of erythrocyte membrane. PMID- 6268122 TI - Cefotaxime: binding affinity to penicillin-binding proteins and morphological changes of Escherichia coli and Pseudomonas aeruginosa. AB - The mechanism of action of a new cephalosporin 7-[2-(2-amino-4-thiazolyl)-2 methoximino]-acetamido cephalosporanate (cefotaxime), was studied with respect to its binding affinities to penicillin-binding proteins (PBPs), and morphological changes of bacteria treated by cefotaxime in vitro. Cefotaxime showed especially high affinity (compared with that pf penicillin G) for Escherichia coli PBP-1A, 1Bs, -3 and -4'and low affinities for PBP-2, -4, -5 and -6. Similar results were obtained with Pseudomonas aeruginosa, in which this compound showed high affinities for PBP-3, -1A, -1B and -2. These results are compatible with morphological observations that at concentrations near its minimum inhibitory concentration or more, this antibiotic induced the formation of filamentous cells of Escherichia coli and Pseudomonas aeruginosa. At higher concentrations or after prolonged incubation, it induced lysis of the cells. PMID- 6268123 TI - Pre- and postsynaptic alpha-adrenergic effects of the antihypertensive drug budralazine. AB - Cardiac presynaptic and vascular postsynaptic alpha-adrenergic effects of 1-[2 (1,3-dimethyl-2-butenylidene)hydrazino]phthalazine (budralazine) were studied in comparison with those of hydralazine. Budralazine was about 3 times less potent than hydralazine in producing tachycardia in spontaneously hypertensive and normotensive rats when compared at equihypotensive doses. In normotensive pithed rats, budralazine at 3 mg/kg i.v. affected neither the tachycardiac response to cardioaccelerator nerve stimulation nor the inhibition of clonidine of the stimulation-induced tachycardia. As the dose was increased to 6 and 12 mg/kg i.v., however, budralazine not only inhibited transiently the sympathetic tachycardia but also enhanced the clonidine bradycardia, although this drug was almost without effect on resting heart rate. These effects of budralazine on the heart rate response in the stimulated rats were partially but significantly antagonized by pretreatment with phentolamine. Hydralazine (3 mg/kg i.v.) differed from budralazine in that its transient inhibition of the stimulation induced tachycardia was not modified by phentolamine and it produced an acceleration of the recovery of clonidine bradycardia as well as an increase in resting heart rate. Budralazine (3--12 mg/kg i.v.), like hydralazine (0.3 and 3 mg/kg i.v.), antagonized pressor responses to noradrenaline and phenylephrine but did not affect the tachycardia produced by both agonists in normotensive pithed rats. Based on these results, a possible mechanism of hypotensive and weak tachycardiac actions of budralazine is discussed in relation to that of hydralazine. PMID- 6268124 TI - [Medical management of colostomies in children]. AB - The author presents his experience in 17 colostomized patients, 15 from high anorectal malformation and 2 from Hirschsprung's disease. He mentions the methods followed to prevent incrustations of the skin, stenosis and prolapse of the colic mouths. the same as the perforation, eventration and evisceration in this type of operations; he stresses the psychological management of the parents and warns pediatricians and pediatric surgeons to keep in mind that the child is a socio psycho-biological unit. Finally, he reports with this type of management. PMID- 6268125 TI - Phosphoglucomutase, adenylate kinase and acid phosphatase polymorphism in some Jewish populations of Israel. AB - The phosphoglucomutase (PGM1) adenylate kinase (AK1) and acid phosphatase (ACP1) phenotypes were studied in Israeli Jews. In total 934 individuals were investigated for AK1 and of these, 926 for PGM1 and 768 for ACP1 isozymes. From the studied individuals, six groups deriving from Eastern, Central and Southern Europe, the Middle East, North Africa and Yemen were formed. The comparison of the phenotype distribution in these groups by the chi-square test failed to indicate any statistically significant differences with respect to PGM1 phenotypes. With respect to AK1 phenotypes, there were statistically significant differences between the Central European group on the one hand and the Yemenite and South European groups on the other (p less than 0.05), and with respect to ACP1--between the Middle Eastern and the Yemenite groups (p less than 0.01). In the studied groups, the frequency of the PGM11 gene varied from 0.6822 (North African group) to 0.7431 (Central European group), of the AK11 gene--from 0.9099 (Central European group) to 0.9698 (Yemenite group) and of the ACPb1 gene--from 0.6710 (Middle Eastern group) to 0.8194 (Yemenite group). The greatest genetic distances were found between the Yemenite group on the one hand and the Middle Eastern, Central European and East European subgroups on the other. PMID- 6268126 TI - Purification of HN glycoprotein of Sendai virus. PMID- 6268127 TI - Age dependent variations in choline and ethanolamine phosphorylating activities of rodents. AB - The substrate concentration-velocity relationship as influenced by age of animal was determined. At all stages of growth of rat and mouse ethanolamine kinase activity responded with a hyperbolic pattern to substrate concentration. Choline kinase on the other hand, underwent "enzyme differentiation". In rat liver up to 4 days of age of animal, in mouse liver up to 7 days and in mouse kidney up to 15 days, choline kinase activity responded with a hyperbolic pattern; but from then onwards the response to substrate concentration was sigmoid. The results obtained pointed to the regulatory nature of choline kinase and a possible distinction between the proteins catalyzing the phosphorylation of the two bases. PMID- 6268128 TI - Effects of dietary fatty acids, prostaglandins and related compounds on the role of platelets in thrombosis. PMID- 6268129 TI - [A study of eosinophilic globular inclusion body in a pyramidal cell of hippocampus (author's transl)]. PMID- 6268130 TI - Pulmonary embolism during surgery for a Wilms' tumour (nephroblastoma). Case report. AB - During resection of a Wilms' tumour in a 10-year-old girl, sudden bradycardia, hypotension and cyanosis developed, leading to cardiac arrest. It was thought that part of the tumour had caused a pulmonary embolus. After prompt resuscitation, cardiopulmonary bypass surgery was started within 20 min. At operation the left pulmonary artery was blocked by a tumour embolus which was removed with a Fogarty catheter. The patient is still alive and well 27 months after her operation. We believe her to be the longest surviving patient of this type. PMID- 6268132 TI - Clinical assessment of neuromuscular transmission. PMID- 6268131 TI - Effect of a new angiotensin converting enzyme inhibitor MK 421 and its lysine analogue on the components of the renin system in healthy subjects. AB - 1 MK 421 and its lysine analogue are two new inhibitors of angiotensin converting enzyme. Ten mg of both compounds were each given p.o. to 12 normotensive volunteers to determine their effect on the various components of the renin angiotensin aldosterone system. 2 Plasma converting enzyme activity decreased to very low levels within 3 to 4 h to recover only slowly over the next 72 h. Plasma angiotensin II and aldosterone also fell but returned to baseline within 24 h, whereas plasma renin activity rose reflecting the low angiotensin II levels. 3 There was a close correlation between both angiotensin II and aldosterone levels and the logarithm of plasma converting enzyme activity demonstrating that angiotensin II and aldosterone fell only when converting enzyme activity was reduced to very low levels. 4 Mean hourly urinary sodium excretion increased markedly 6 to 10 h post-drug, while blood pressure decreased slightly. Both drugs were well tolerated. 5 Thus 10 mg of MK 421 or its lysine analogue given orally are effective and long acting angiotensin converting enzyme inhibitors. PMID- 6268134 TI - Hydralazine-induced peripheral neuropathy seen in a Japanese slow acetylator patient. PMID- 6268133 TI - The early and late effects of digoxin treatment on the sodium transport, sodium content and Na+K+- ATPase or erythrocytes. AB - 1 Erythrocyte sodium content, sodium transport (ouabain sensitive sodium flux Eos, and ouabain sensitive efflux rate constant ERCos) sodium, potassium activated ouabain sensitive adenosine triphosphatase (Na+K+ATPase) and plasma digoxin were measured in patients during acute digitalisation and in patients who were on long-term digoxin treatment. 2 In the six patients who were studied during digitalisation, the ERCos and Na+K+ATPase activity decreased and erythrocyte sodium content increased during days 2-4 treatment, but there was no change in Eos. 3 In 39 patients on long term digoxin therapy (2-119 months) the erythrocyte sodium content was normal, but the erythrocyte Na+K+ATPase activity was higher than the control group. When the results from these 39 patients were divided according to the duration of treatment it was found that the erythrocyte sodium content was higher in patients treated for 2-4 months than in patients treated for longer periods and the erythrocyte Na+K+ATPase activity increased with duration of treatment. In eight patients (duration of treatment greater than 29 months) in whom ERCos and Eos were measured, ERCos and Eos were higher than the control group. 4 The results suggest that the effects of digoxin on erythrocytes which occur during acute digoxin treatment do not persist in the long term. 5 The possible explanation for the higher ERCos, Eos and Na+K+ATPase activity in patients treated with digoxin for more than 2 months is discussed. PMID- 6268135 TI - Lymphocytes infiltrating human breast cancers lack K-cell activity and show low levels of NK-cell activity. AB - Lymphocytes infiltrating human primary mammary carcinomas lack ADCC and show low levels of natural cytotoxicity. The peripheral blood lymphocytes, however, show a variable but prominent level of cytotoxicity. Lymphocyte preparations from breast tumours, when mixed with autologous blood lymphocytes, significantly suppress their prominent killer- (K- and NK-) cell activities. PMID- 6268136 TI - Effects of cyclic-nucleotide derivatives on the growth of human colonic carcinoma xenografts and on cell production in the rat colonic crypt epithelium. AB - Previous studies have shown that various amine hormones are able to influence the growth rate of human colorectal carcinomas propagated as xenografts in immune deprived mice, and it is now well known that the effects of many amine and other hormones are mediated by cyclic nucleotides, acting as second messengers within cells. In the present study the influence of various derivatives of cyclic adenosine monophosphate and cyclic guanosine monophosphate on the growth of two different lines of colorectal cancer growing in immune-deprived mice, and on the cell production rate in the colonic crypt epithelium of the rat, was assessed. Growth of each tumour line, as well as crypt-cell production, was suppressed by treatment wit N6O2' dibutyryl and N6 monobutyryl derivatives of cyclic adenosine monophosphate. Dibutyryl cyclic guanosine monophosphate, on the other hand, was found to promote the growth of Tumour HXK4 and to promote crypt cell production, but to have no significant effect on Tumour HXM2. PMID- 6268137 TI - Soft-tissue necrosis induced by extravasated cancer chemotherapeutic agents: a study of active intervention. PMID- 6268138 TI - Changes in energy metabolism, structure and function in alveolar macrophages under anaerobic conditions. AB - To determine whether the change in energy metabolism of guinea-pig alveolar macrophages (AM) would alter their function to resemble peritoneal macrophages (PM), AM were exposed to strict anaerobic environments for 96 h. Exposure of cultivated AM to hypoxic conditions resulted in a decreased activity of cytochrome oxidase, a key enzyme in oxidative phosphorylation, whereas pyruvate kinase activity, a key enzyme in glycolysis, increased to levels observed in PM. Under hypoxic conditions the total mitochondrial structure available for respiratory activity also decreased in the glycolytic energy-dependent AM. Accompanying the shift in energy metabolism, adaptive changes in the functional responses of lectin-receptor activity occurred in the AM exposed to hypoxic conditions. Culture of AM in an anaerobic environment led to a loss in their ability to mobilize their lectin receptors in response to cytochalasin B, whereas AM maintained in an aerobic environment could mobilize their receptors in response to either cytochalasin B and D. Alterations in O2 tension affect AM metabolism, morphology and function and indicate that the AM is able to change its energy metabolism according to environmental circumstances. PMID- 6268139 TI - Familial bleeding tendency with partial platelet thromboxane synthetase deficiency: reorientation of cyclic endoperoxide metabolism. AB - Three family members from three successive generations presented with a moderate bleeding tendency and a functional platelet defect. They had absent aggregation with arachidonic acid (0.6--3 microM), reversible aggregation with ADP (4 microgram) and cyclic endoperoxide analogues, single wave aggregation only with adrenaline (5.4 microgram) and a prolonged template bleeding time (> min). Malondialdehyde formation was reduced after N-ethylmaleimide stimulation (2--6 nmol/10(9) platelets; control values 8--12 nmol) and serum thromboxane B2 values were reduced (33--101 ng/ml; control values 200--700 ng/ml). When the platelets were incubated with [3H]arachidonic acid the final metabolite of the lipoxygenase pathway (HETE) was produced in normal amounts but the production of thromboxane B2 and HHT was decreased whereas prostaglandin F2a, and E2 and probably D2 were increased. Evidence for enhanced production of prostaglandin D2 was also provided by the rise in the patient's platelet cyclic AMP levels following stimulation with arachidonic acid. The patient's washed platelets stimulated the production of 6-keto PGF 1a by aspirin-pretreated cultured bovine endothelial cells. The plasma levels of 6-keto PGF1a (439--703 pg/ml; normal 181 +/- 46 pg/ml) were raised. The decreased production of thromboxane B2, HHT and malondialdehyde and increased formation of prostaglandin F2a, E2, D2 and of 6-keto PGF1a are compatible with a partial platelet thromboxane synthetase deficiency and reorientation of cyclic endoperoxide metabolism. The markedly prolonged bleeding time would result not only from reduced formation of thromboxane A2 but also from increased production of the aggregation inhibiting prostaglandins PGI2 and PGD2. PMID- 6268140 TI - Penicillanic acid sulfone: an unexpected isotope effect in the interaction of 6 alpha- and 6 beta-monodeuterio and of 6,6-dideuterio derivatives with RTEM beta lactamase from Escherichia coli. AB - Penicillanic acid sulfone (1) is both a substrate and an inactivator of the RTEM beta-lactamase. About 7000 hydrolytic events occur before enzyme inactivation. The 6,6-dideuterio sulfone shows a 3-fold acceleration of both the hydrolysis reaction and the enzyme inactivation. The kinetic and spectroscopic results are nicely accommodated by a scheme in which a transiently stable intermediate is formed in an isotopically sensitive step. The deuterated material partitions less readily toward this transiently stable intermediate by virtue of a primary isotope effect, and more enzyme is then available for the hydrolysis and inactivation pathways. Use of the stereospecifically monodeuterated sulfones shows that the 6 beta hydrogen is preferentially abstracted in the formation of the transiently stable intermediate and allows a detailed picture of the interaction of the sulfone and the beta-lactamase to be drawn. The crystal structures of both the labeled and unlabeled compounds are reported. PMID- 6268141 TI - Penicillanic acid sulfone: interaction with RTEM beta-lactamase from Escherichia coli at different pH values. AB - The interaction of the sulfone of penicillanic acid with the TEM-2 beta-lactamase from Escherichia coli has been investigated as a function of pH between pH 7.0 and 9.6. The first-formed acyl-enzyme suffers one of three fates: deacylation, tautomerization to a bound enamine that transiently inhibited the enzyme, and a process (possibly transimination) that leads to enzyme inactivation. The observed changes in ultraviolet absorbance are consistent with the initially observed product of deacylation being the enamine tautomer (4) of the imine from malonsemialdehyde and penicillamine sulfinate. The same enamine can be generated nonenzymically from the sulfone at high pH. The transiently inhibited enzyme appears to be the same enamine attached to the enzyme by an ester linkage. The rather complex kinetic behavior can be deconvuluted by exploiting the effect of pH on the partitioning of the acyl-enzyme between deacylation and the transiently inhibited form of the enzyme. The pathways followed by penicillanic acid sulfone provide a model for the behavior of a number of other reagents that inactivate the beta-lactamase. PMID- 6268142 TI - Inhibition of the BamHI cleavage and unwinding of pBR322 deoxyribonucleic acid by the antitumor drug cis-dichlorodiammineplatinum(II). PMID- 6268143 TI - Preparation of milligram amounts of 21 deoxyribonucleic acid restriction fragments. AB - Twenty-one DNA restriction fragments ranging in size from 12 to 880 base pairs (bp) were purified to homogeneity in milligram amounts. The developments which facilitated this work were (a) procedures for the rapid preparation of gram quantities of pure recombinant plasmid DNAs, (b) selective poly(ethylene glycol) (PEG) precipitation of DNAs according to broad classes of lengths, and (c) large scale high-pressure liquid chromatography on RPC-5 for the purification of fragments to homogeneity. The 95- and 301-bp sequences from the lactose control region of Escherichia coli were cloned into the single EcoRI site of pVH51 in up to four copies per plasmid. These tandem inserts are separated by EcoRI sites and have a head to tail orientation in all cases. A total of 50 and 90 mg of th 95- and 301-bp fragments, respectively, were prepared from 300-L fermentations of E. coli cells transformed with these plasmids. A rapid and improved method, which can easily be scaled up, for the purification of plasmids and DNA restriction fragments was developed. Also, the linear pVH51 vector DNA was digested with HaeIII to yield fragments ranging in size from 12 to 880 bp. The five smaller fragments (from 12 to 180 bp) were purified quantitatively by a selective PEG precipitation enrichment step followed by RPC-5 column fractionation. The larger fragments (245-880 bp) were prepared in milligram amounts. Ten subfragments from the 301-bp lac fragment were prepared by HpaII, HinfI, or HaeIII/AluI digestions followed by separation of the reaction products on RPC-5. PMID- 6268145 TI - A 300-MHz proton nuclear magnetic resonance investigation of deoxyribonucleic acid restriction fragments: dynamic properties. PMID- 6268144 TI - A 300- and 600-MHz proton nuclear magnetic resonance investigation of a 12 base pair deoxyribonucleic acid restriction fragment: relaxation behavior of the low field resonances in water. PMID- 6268146 TI - Amino acid sequence of p15 from avian myeloblastosis virus complex. AB - The complete amino acid sequence of the p15 gag protein from avian myeloblastosis virus (AMV) complex has been determined by sequential Edman degradation of the intact molecule and of peptide fragments generated by limited tryptic cleavage, cleavage with staphylococcal protease, and cyanogen bromide cleavage. AMV p15 is a single-chain protein containing 124 amino acids. The charged amino acids tend to be clustered in the primary structure. p15 contains a single cysteine at position 113 which may be essential for the p15 associated proteolytic activity. However, p15 shows no appreciable sequence homology with papain or other classical thiol proteases. PMID- 6268147 TI - Ribosomal ribonucleic acid repeat unit of Acanthamoeba castellanii: cloning and restriction endonuclease map. AB - The repeat unit coding for the precursor to 18S, 5.8S, and 26S ribosomal ribonucleic acids (rRNAs) has been cloned from the free-living soil amoeba Acanthamoeba castellanii. The cloned deoxyribonucleic acid (DNA) was mapped with 11 restriction endonucleases and by R-loop mapping. The entire repeat unit is 12 kbp (kilobase pairs) in length and contains sites for EcoRI, SmaI, BglII, SstI, Bam-HI, PstI, KpnI, HindIII, and XbaI but not for XhoI or SalI. All of the repeat units in the nuclear DNA appear to be identical, and no introns were detected. However, the regions which code for the two RNAs which comprise the 26S RNA are separated by a gap of approximately 200 base pairs. Unlike some other lower eukaryotes, the 5S RNA gene is not linked to this repeat unit. A fragment of the repeat unit which contains the initiation sequence of the putative precursor has been subcloned into pBR322 for use in vitro transcription studies. PMID- 6268148 TI - Phenylalanyl-tRNA synthetase of baker's yeast. Modulation of adenosine triphosphate-pyrophosphate exchange by transfer ribonucleic acid. AB - Native and modified phenylalanine transfer ribonucleic acid (tRNAPhe) can modulate phenylalanine-dependent adenosine triphosphate--inorganic [32P]pyrophosphate (ATP--[32P]PPi) exchange activity via inhibition of adenylate synthesis. Inhibition is visualized if concentrations of L-phenylalanine, ATP, and pyrophosphate are subsaturating. In the proposed mechanism, tRNAPhe is a noncompetitive inhibitor at conditions where only one of the two active sites per molecule of enzyme is occupied by L-phenylalanine, ATP, and pyrophosphate. At saturating concentrations of these reactants, both active sites are occupied and, according to the model, inhibition is eliminated. Occupation by these reactants is assumed to follow homotropic negative cooperativity. The type of effects depends on modification of tRNAPhe. Native tRNAPhe, tRNA2'-dAPhe, and tRNAoxi redPhe are inhibitors, tRNAPhepCpC has no effect, and tRNAoxPhe is an activator. Kinetics of activation by tRNAoxPhe are slow, following the time course of Schiff base formation and subsequent reduction by added cyanoborohydride. Besides showing that a putative enzyme amino group is nonessential for substrate binding and adenylate synthesis, this result may suggest that an enzyme amino group could interact with the 3'-terminal adenyl group of cognate tRNA. In the case of asymmetrical occupation of the enzyme active sites by all of the small reactants ATP, L-phenylalanine, and pyrophosphate, the interaction with the amino group might trigger the observed noncompetitive inhibition of the pyrophosphate exchange by tRNAPhe. PMID- 6268149 TI - Isolation and identification of 23,25-dihydroxyvitamin D3, an in vivo metabolite of vitamin D3. AB - Vitamin D supplemented rats produce a metabolite of 25-hydroxy[3 alpha-3H]vitamin D3 that is easily separated from known metabolites by using high-performance liquid chromatography. The production of this metabolite in vivo as well as 1,25 dihydroxyvitamin D3, 24(R),25-dihydroxyvitamin D3, and 25-hydroxyvitamin D3 26,23 lactone is largely if not totally eliminated by nephrectomy. Kidney homogenates from vitamin D supplemented chickens incubated with 25-hydroxyvitamin D3 produce significant quantities of the new, unknown metabolite. This metabolite was isolated in pure form from such incubation mixtures by using both straight-phase and reversed-phase high-performance liquid chromatography. This metabolite has been positively identified as 23,25-dihydroxyvitamin D3 by ultraviolet absorption spectrophotometry, mass spectrometry, and derivatization. This structure was confirmed by chemical synthesis of both C-23 stereoisomers. Although the natural product exactly comigrates with one of the synthetic isomers, the exact stereochemistry of the natural product remains unknown. It is possible that this new metabolite is an intermediate in the biosynthesis of 25-hydroxyvitamin D3 26,23-lactone. PMID- 6268150 TI - Acetaldehyde--enkephalins: structure proof and some conformational deductions from one- and two-dimensional proton nuclear magnetic resonance spectra. AB - The structure of the adduct formed by reaction of acetaldehyde and Met5 enkephalin has been determined by analysis of 400-MHz proton spectra: two dimensional J spectroscopy was used to resolve and measure virtually all the overlapping resonances, and decoupling difference spectroscopy was used to assign the resonances. Suitable manipulation of the two-dimensional data allowed analysis of alpha-CH resonances which were completely buried under a water signal and of amide NH resonances which overlapped in both dimensions. The adduct was shown to be a mixture of two diastereoisomers, each containing a 2 methylimidazolidin-4-one ring formed by condensation of an acetaldehyde molecule with the N-terminal amino group and Gly2 amide nitrogen. Analysis of the NMR data suggests that the folded conformation characteristic of native enkephalins in dimethyl-d6 sulfoxide is not important in these derivatives. PMID- 6268151 TI - Role of matrix protein in assembling the membrane of vesicular stomatitis virus: reconstitution of matrix protein with negatively charged phospholipid vesicles. AB - The matrix (M) protein of vesicular stomatitis virus (VSV) was reconstituted into phospholipid vesicles by detergent dialysis. Reconstitution of the positively charged M protein occurred only in the presence of negatively charged phospholipids such as phosphatidylserine, phosphatidic acid, or phosphatidylinositol. Preformed vesicles containing negatively charged phospholipids also bound free M protein. Derivatization of the positively charged lysines in M protein with acetic anhydride or succinic anhydride prevented M protein reconstitution but did not affect the biological property of M protein to inhibit in vitro VSV transcription. An additional indication of the electrostatic nature of the M protein binding to the vesicles was that M protein could not be reconstituted in the presence of 0.5 M NaCl. Nonelectrostatic forces also appear to be involved in the association of the M protein with vesicles, since previously reconstituted M protein remained associated with the vesicles upon subsequent exposure to 0.5 M NaCl. PMID- 6268152 TI - Epidermal growth factor: relationship between receptor down regulation in cultured NRK cells and epidermal growth factor enhancement of phosphorylation of a 170000 molecular weight membrane protein in vitro. AB - Incubation of confluent nondividing NRK cells in serum-free media with unlabeled epidermal growth factor (EGF) leads to a reduction in the specific binding capacity for 125I-labeled EGF. This modulation of the binding capacity for 125I labeled EGF by unlabeled EGF, termed receptor down regulation, was dependent on EGF concentration and time. Membranes from untreated NRK cells have a phosphorylating system which catalyzed in vitro the phosphorylation of numerous membrane components; this phosphorylating system was stimulated by EGF. Although EGF enhanced the phosphorylation of many membrane proteins, one major component with Mr 170K and a minor band of Mr 150K were primarily affected. A comparison of the membrane phosphoproteins of untreated and down-regulated cells by in vitro phosphorylation and NaDodSO4 gel electrophoresis revealed that down regulation of EGF receptors results in a specific decrease in 32P phosphorylation of the 170K- and 150K-dalton components to subsequent stimulation with EGF in vitro. We further characterized the modulation of phosphorylation of the 170K protein by down regulation with EGF and found it to be dependent on EGF concentration and time. These studies demonstrated a correlation between the loss of 125I-labeled EGF binding activity by the cells and the loss of the vitro EGF-dependent 32P phosphorylation of the 170K-dalton membrane protein. In addition, the results suggest that the major 170K Mr phosphoprotein band is a component of the receptor for EGF which is a substrate of the phosphorylation reaction. PMID- 6268153 TI - Conformations of oxidized cytochrome c oxidase. AB - Oxidized cytochrome c oxidase is shown to exist in three conformations in addition to the transient "g5" conformation previously reported [Shaw, R. W., Hansen, R. E., & Beinert, H. (1978) J. Biol. Chem. 253, 6637-6640]. The "resting" and "g12" conformations are distinguished by an NO-induced cytochrome a3 electron paramagnetic resonance (EPR) signal and an EPR signal at g' = 12, respectively. The "oxygenated" conformatin exhibits an unusual EPR signal in the presence of fluoride and is identical with the "oxygenated" state first discovered by Okunuki et al. [Okunuki, K., Hagihora, B., Sekuzu, I., & Horio, T. (1958) Proc. Int. Symp. Enzyme Chem., Tokyo, Kyoto, 264]. It is proposed that when the reduced enzyme is reoxidized by dioxygen, the oxidized enzyme first relaxes from the "g5" into the "oxygenated" conformation after which a percentage of the molecules slowly relax into the "g12" conformation. The "resting" conformation is not formed when the enzyme is reoxidized. On the basis of the EPR observations, it is proposed that these various conformations of the oxidized enzyme differ in the structure of the cytochrome a3--Cua3 site. Structures for the cytochrome a3--Cua3 site are proposed for each conformation, and a mechanism by which these conformations undergo interconversion among themselves is described. PMID- 6268154 TI - Proton nuclear magnetic resonance study of an active pentapeptide fragment of ubiquitin. AB - The aqueous solution conformation of Tyr-Asn-Ile-Gln-Lys (UB5) corresponding to positions 59-63 of the polypeptide, ubiquitin, has been investigated by proton NMR. Like the parent protein, UB5 induces nonspecifically both T and B lymphocyte differentiation. The various NH and CH resonances of this pentapeptide have been assigned, and its solution conformation has been probed through a study of chemical shift variations with pH, temperature dependence of amide hydrogen chemical shifts, vicinal NH--C alpha H and C alpha H--C beta H2 coupling constant data, and amide hydrogen-exchange rates. The latter were measured in H2O by using a combination of transfer of solvent saturation and saturation recovery NMR experiments. The data are compatible with the assumption of a highly motile dynamic equilibrium among different conformations for this peptide. The various secondary amide hydrogens remain essentially exposed to the solvent. The temperature-dependence study of the amide hydrogen chemical shifts also did not reveal any strong internal hydrogen bonds. A rotamer population analysis of tyrosine and asparagine side chains suggests that two of the rotomers are predominantly populated for each of these residues. From these results, a picture emerges of the dynamic conformation of UB5 in aqueous solution. PMID- 6268155 TI - Virus-induced fusion of human erythrocyte ghosts. I. Effects of macromolecules on the final stages of the fusion reaction. AB - Human erythrocyte ghosts prepared by hypotonic hemolysis can be fused by Sendai virus, provided that certain macromolecules (bovine serum albumin, dextran and others) are sequestered in the ghosts. Since fusion of the ghosts is dependent on intactness of the F(fusion)-glycoprotein of the virion, and since the other requirements for this reaction are also similar to those for the Sendai virus induced fusion of intact erythrocytes, this system can be used as a model for the Sendai virus-induced cell fusion reaction. Sequestered macromolecules seem to be required for rounding of locally fused ghosts. Under low osmotic swelling conditions, such as use of ghosts sealed without macromolecules or using bovine serum albumin-loaded ghosts sealed in the presence of external macromolecules, no apparently complete cell fusion (large spherical polyghost formation) could be observed. Even under these conditions, however, occurrence of local cell fusion could be demonstrated either by transfer of fluorescent-labeled albumin from one ghost to an other, or by observation of polyghost formation after osmotic swelling in the cold. Thus, final stages of the fusion reaction can be divided into local cell-cell fusion which could not be observed by phase-contrast microscopy, and rounding (i.e. formation of spherical polyghosts). For the observation of fusion of ghosts, the last step seems to be important. PMID- 6268157 TI - Glycoprotein characteristics of the sodium channel saxitoxin-binding component from mammalian sarcolemma. AB - The saxitoxin-binding component of the excitable membrane sodium channel exhibits glycoprotein characteristics as evidenced by its specific interaction with various agarose-immobilized lectins. The detergent-solubilized saxitoxin-binding component interacts quantitatively with immobilized wheat germ agglutinin and concanavalin A and fractionally with immobilized Lens culinaris hemagglutinin and Ricinus communis agglutinin. These lectins preferentially bind N acetylglucosamine and sialic acid (wheat germ agglutinin), mannose (concanavalin A and Lens cunilaris) and galactose (Ricinus communis). Removal of terminal sialic acid residues by neuraminidase markedly decreases binding to immobilized wheat germ agglutinin but uncovers sites capable of interacting with lectins specific for galactose and N-acetylgalactosamine. beta-N-acetylglucosaminidase, an exoglycosidase, has no effect on the binding of the channel protein to wheat germ agglutinin. Similarly, phospholipase C has no effect on binding of the solubilized toxin binding component to this lectin. Neither wheat germ agglutinin nor concanavalin A free in solution alters the number of toxin binding sites or their affinity for toxin. The sodium channel saxitoxin-binding component to wheat germ agglutinin. Similarly, phospholipase C has no effect on binding of the solubilized toxin binding component to this lectin. Neither wheat germ agglutinin nor concanavalin A free in solution alters the number of toxin binding sites or their affinity for toxin. The sodium channel saxitoxin-binding component to wheat germ agglutinin. Similarly, phospholipase C has no effect on binding of the solubilized toxin binding component to this lectin. Neither wheat germ agglutinin nor concanavalin A free in solution alters the number of toxin binding sites or their affinity for toxin. The sodium channel saxitoxin-binding component appears to be a glycoprotein containing terminal sialic acid residues and internal mannose, galactose, N-acetylglucosamine, and N-acetylgalactosamine residues. The toxin binding site is spatially separated from the binding sites for the lectins studied. The effect of these sugar moieties must be considered when evaluating the biophysical parameters of the sodium channel. PMID- 6268156 TI - Interfacial preference of anesthetic action upon the phase transition of phospholipid bilayers and partition equilibrium of inhalation anesthetics between membrane and deuterium oxide. AB - The half-height linewidth (v 1/2) of the 1H-NMR spectra of dipalmitoylphosphatidylcholine vesicles changes abruptly at the phase transition temperature. In the absence of inhalation anesthetics, proton signals from the choline head group (hydrophilic interface) and acyl-chain tails (lipid core) change at the same temperature of 39.6 degrees C. The present study compared the effect of four inhalation anesthetics, i.e., methoxyflurane, chloroform, halothane and enflurane, upon the ligand-induced phase transition of phosphatidylcholine vesicle membranes at 37 degrees C. The anesthetics showed differential action upon the phase transition of the phospholipid vesicle membranes between the lipid core and the hydrophilic interface. The concentrations of anesthetics which induced the phase transition of the lipid core were about 2-fold greater than those required for the phase transition of the interfacial choline head groups. From the area under the proton signals of inhalation anesthetics in the NMR spectra, the maximum solubilities of methoxyflurane, chloroform and halothane in 2H2O at 37 degrees C were determined to be 0.671 . 10(-4), 2.637 . 10(-4) and 1.398 . 10(-4) (expressed as mole fractions), or 3.35, 13.17 and 6.98 mmol/1000 g 2H2O, respectively. The solubilities of the anesthetic vapor in 2H2O expressed as mole fractions according to Henry's law ere 9.586 . 10(-4), 6.432 . 10(-4) and 2.311 10(-4)/atm (1.013 . 10(5) Pa) partial pressure, respectively. The presence of phospholipid vesicles in 2H2O increased the solubility of the inhalation anesthetics. From difference between solubility in 2H2O and a dipalmitoylphosphatidylcholine vesicle suspension, the partition coefficients of methoxyflurane, chloroform and halothane between the phospholipid vesicle membranes and 2H2O were estimated. These values, calculated from the mole fractions, were 3364, 1660 and 3850, respectively at 37 degrees C. PMID- 6268158 TI - Hepatic receptor for asialo-glycoproteins. Ultrastructural demonstration of ligand-induced microaggregation of receptors. AB - Endocytosis of asialo-glycoproteins in hepatocytes is mediated by a lectin-like receptor with specificity for D-galactose. Early events of receptor-ligand interactions have been studied by ultrastructural analysis. Hepatocytes were isolated from the rat liver by collagenase perfusion and incubated with a galactosylated electron dense marker (gold-Gal-BSA, glactosylated bovine serum albumin adsorbed onto colloidal gold particles). Initial binding of gold-Gal-BSA particles occurs to receptors diffusely distributed at hepatic microvilli of the former space of Dise. No lectin activity was found in membrane areas that had formed in situ the region of hepatic cell contact or bile canaliculi. Microaggregation of receptor-ligand complexes is seen as an early consequence of particle binding. Microaggregates contain 2-5 particles and are located outside coated pits. After prolonged incubation larger clusters are formed, these are found associated with coated membrane areas. It is concluded that at least three steps precede the uptake of galactosylated proteins by hepatocytes. These are: (i) binding of ligand at diffusely distributed binding sites; (ii) local microaggregation of receptor-ligand complexes; (iii) formation of larger clusters and association with coated pits. PMID- 6268159 TI - Microinjection of arginase into enzyme-deficient cells with the isolated glycoproteins of Sendai virus as fusogen. AB - A method of introducing enzymes into the cytoplasm of fibroblasts in culture is described. Erythrocytes obtained from normal and arginase-deficient individuals were loaded with arginase in vitro and fused to arginase-deficient mouse and human fibroblasts. Erythrocyte ghost-fibroblast fusion was quantified by a 14C radioactive assay for arginase in solubilized fibroblasts. Fusion was successfully induced by Sendai virus and also by the isolated glycoproteins of Sendai virus. After fusion the arginase activity associated with the Fibroblasts was 700--1500 U of arginase/mg of cell protein; this enzyme activity was 5- to 10 times higher than that normally found in the fibroblasts. The enrichment in arginase activity indicated that between four and ten ghosts had fused per fibroblast. The use of isolated viral proteins to mediate the transfer of enzymes into cells in vivo might alleviate clinical complications inherent in the use of whole virions. The enzyme replacement technique described in this report for a hyperargininemic model cell system should be applicable to the group of inborn errors of metabolism characterized by deficiency of an enzyme normally localized in the cytoplasmic compartment of cells. PMID- 6268160 TI - Isolation and initial characterization of a lymphocyte cap structure. AB - A method for isolating the cap structure induced by polycationized ferritin on the surface of mouse T-lymphoma cells is described. The procedure, based on the 'density perturbation' approach designed by Wallach and co-workers (Wallach, D.F.H., Kranz, B., Ferber, E. and Fischer, H. (1972) FEBS Lett. 21, 29-33), involves a simple, one-step density gradient centrifugation using metrizamide as the gradient material. The isolated polycationized ferritin cap fraction is approx. 20-fold enriched in plasma membrane relative to the whole cell homogenate and is apparently free of all uncapped membrane. Our initial analysis of the protein composition of the isolated cap structure indicates that there are approx. 30 membrane-bound polypeptides specifically associated with the polycationized ferritin cap fraction. Interestingly, there are at least four phosphorylated membrane-bound polypeptides (mol.wt. approximately 130 000, 100 000, 30 000 and 20 000) which are preferrentially accumulated in the cap fraction. These findings provide further evidence for the selective redistribution of certain surface membrane proteins during lymphocyte capping. PMID- 6268161 TI - Dynamic states of phospholipids in Escherichia coli B membrane. Electron spin resonance studies with biosynthetically generated phospholipid spin labels. AB - Mobility of phospholipid hydrocarbons in the Escherichia coli B membrane fractions was studied by labeling phosphatidylethanolamine or phosphatidylglycerol in situ by biosynthetic incorporation of the spin label. For this purpose, CDP-diacylglycerol spin label was synthesized from phosphatidic acid spin label and cytidine 5'-phosphoromorpholidate and purified by thin-layer chromatography. DCP-diacylglycerol spin label was then incorporated into phospholipids biosynthetically. ESR spectra of these E. coli B membrane fractions showed that phosphatidylglycerol tended to interact with membrane proteins through the mediation of Mg2+, whereas phosphatidylethanolamine had less of this tendency and was more involved in the formation of the bulk of the bilayer continuum of the membrane. These conclusions were also supported by labeling membranes with exogenous spin-labeled phospholipids, although there was some indication that exogenous phospholipids were incorporated into sites different from the sites of incorporation of phospholipids newly synthesized in situ. PMID- 6268162 TI - Active accumulation and exchange transport of chloride in astroglial cells in culture. AB - Chloride transport in primary cultures of astroglial cells from rat brain shows saturation kinetics, is inhibited by SITS (4-acetamido-4'-isothiocyanostilbene 2,2'-disulfonic acid), and exchanges with HCO-3. These properties are similar to those of the anion exchange system in erythrocytes. Estimated of intracellular C1 concentration([C1-]i) in the primary cultures give values in the range of 31 to 43 mM, which are 3- to 5-times greater than predicted from equilibration with an average measured membrane potential of -70 mV, suggesting that these cells also actively accumulate Cl-. PMID- 6268163 TI - Initiation of fusion and disassembly of Sendai virus membranes into liposomes. AB - Sendai virus penetration into liposomes consists of two steps which are fusion of the viral and liposomal membranes and viral disassembly. Penetration can occur in less than one minute. The virus first causes a liposome to envelop it and then fuses with the leading edge of the developing vacuole. Viral disassembly does not follow immediately but requires release of virus-receptor binding and probably also requires changes in the association between viral proteins. PMID- 6268164 TI - Modification of the tetrodotoxin receptor in Electrophorus electricus by phospholipase A2. AB - The effects of phospholipase A2 treatment on the tetrodotoxin receptors in Electrophorus electricus was studied. (1) The binding of [3H]tetrodotoxin to electroplaque membranes was substantially reduced by treatment of the membranes with low concentrations of phospholipase A2 from a number of sources, including bee venom, Vipera russelli and Crotalus adamanteus and by beta-bungarotoxin. (2) Phospholipase A2 from bee venom and from C. adamanteus both caused extensive hydrolysis of electroplaque membrane phospholipids although the substrate specificity differed. Analysis of the phospholipid classes hydrolyzed revealed a striking correlation between loss of toxin binding and hydrolysis of phosphatidylethanolamine but not of phosphatidylserine. (3) The loss of toxin binding could be partially reversed by treatment of the membranes with bovine serum albumin, conditions which are known to remove hydrolysis products from the membrane. (4) Equilibrium binding studies on the effects of phospholipase A2 treatment of [3H]tetrodotoxin binding showed that the reduction reflected loss of binding sites and not a change in affinity. (5) These results are interpreted in terms of multiple equilibrium states of the tetrodotoxin-receptors with conformations determined by the phospholipid environment. PMID- 6268165 TI - The effect of micrococcal nuclease and DNAase I on bulk and 5 S RNA synthesis in isolated HeLa cell nuclei. PMID- 6268166 TI - Involvement of basic amino acids in the activity of a nucleic acid helix destabilizing protein. AB - Under conditions of low ionic strength, ribonuclease A, which binds more tightly to single- than to double-stranded DNA, lowers the melting temperature of DNA helices (Jensen and von Hippel (1976) J. Biol. Chem. 251, 7198-7214). The effects of chemical modification of lysine and arginine residues on the helix destabilizing properties of this protein have been examined. Removal of the positive charge on the lysine epsilon-amino group, either by maleylation or acetylation, destroys the ability of RNAase A to lower the Tm of poly[d(A-T)]. However, reductive alkylation of these residues, which has not effect on charge, yields derivatives which lower the Tm by only about one-half that seen with unmodified controls. Phenylglyoxalation of arginines can largely remove the Tm depressing activity of RNAase A. RNAase S, which is produced by cleavage of RNAase A between amino acids 20 and 21, possesses DNA helix-destabilizing activity comparable to that of the parent protein, whereas S-protein (residues 21 124) increases poly[d(A-T)] Tm and S-peptide (1-20) has no effect on Tm. These results suggest that specific location of several basic amino acids situated on the surface of RNAase A is largely responsible for this protein's DNA melting activity. PMID- 6268167 TI - An electron spin resonance investigation and molecular orbital calculation of the anion radical intermediate in the enzymatic cis-trans isomerization of furylfuramide, a nitrofuran derivative of ethylene. AB - The enzymatic cis-trans isomerization of nitrofuran derivatives has been proposed to occur via the formation of a radical anion intermediate. ESR investigations, in conjunction with intermediate neglect of differential overlap (INDO) molecular orbital calculations, support this concept by demonstrating the enzymatic generation of cis and trans radical anions of 3-(5-nitro-2-furyl)-2-(2-furyl) acrylamide. The INDO calculations further indicate that the rotational barrier between the cis and trans anion radicals of this compound is only 5--10 kcal/mol, whereas a 70 kcal/mol barrier exists for the parent geometric isomers. Hyperfine splitting constants for the cis-trans conformers have been assigned on the basis of INDO calculations. Surprisingly, only the nitrogen hyperfine splitting of the nitro group is distinguishably different in the two conformers, a result which is not inconsistent with the INDO calculations. PMID- 6268168 TI - The autophosphorylation reaction in the mechanism of activation of pig brain cyclic AMP-dependent protein kinase. AB - Autophosphorylation of cyclic AMP-dependent protein kinase (ATP: protein phosphotransferase, EC 2.7.1.37) was shown to occur via an intramolecular mechanism: the regulatory subunit undergoes phosphorylation only within the holoenzyme. The phospho form of the catalytic subunit has the capacity to phosphorylate the regulatory subunit. The phosphotransferase reaction and the reaction of autophosphorylation were found to proceed with the involvement of the same active site. The activation constant of phospho- and dephosphoprotein kinase under the influence of cyclic AMP and the dissociation constant of the cyclic AMP complex with phospho- and dephospho forms of the holoenzyme were estimated. Autophosphorylation was demonstrated to lead to almost complete dissociation of the holoenzyme under the influence of cyclic AMP. Circular dichroism spectra of the phosphorylated and non-phosphorylated forms of protein kinase were studied. The relative content of the secondary structure elements in proteins was estimated and conformational changes were detected in the enzyme upon its interaction with cycli AMP. The anti-conformation of the cyclic nucleotide fixed in the complex with the phospho form of the regulatory subunit is suggested. PMID- 6268169 TI - 1H-NMR studies on the binding subsites of bovine pancreatic ribonuclease A. AB - The titration curves of the C-2 histidine protons of an RNAase derivative (a covalent derivative obtained by reaction of bovine pancreatic RNAase A (EC 3.1.27.5) with 6-chloropurine 9-beta-D-ribofuranosyl 5'-monophosphate) were studied by means of 1H-NMR spectroscopy at 270 MHz. The interaction of natural (5'AMP, 5'GMP, 5'IMP) and halogenated purine mononucleotides (cl6RMP, br8AMP) with RNAase A was also monitored by using the same technique. The slight change observed in the pK values of the active centre histidine residues of the RNAase derivative, with respect to those in the native enzyme, can be considered as evidence that the phosphate of the label does not interact directly either with His-12 or 119 in the p1 site, but the p2 site as proposed previously (Pares, X., Llorens, R., Arus, C. and Cuchillo, C.M. (1980) Eur. J. Biochem. 105, 571--579). Lys-7 and/or Arg-10 are proposed as part of the p2 phosphate-binding subsite. The pK values of His-12 and 119 and the shift of an aromatic resonance of the native enzyme found on interaction with some purine nucleotides, can be interpreted by postulating that the interaction of 5'AMP, 5'GMP and 5'IMP takes place not only in the so-called purine-binding site B2R2p1 but also in the primary pyrimidine binding site B1R1 and p0 of RNAase A. PMID- 6268170 TI - Evidence for an essential arginine residue at the active site of Escherichia coli acetate kinase. AB - Escherichia coli acetate kinase (ATP: acetate phosphotransferase, EC 2.7.2.1.) was inactivated in the presence of either 2,3-butanedione in borate buffer or phenylglyoxal in triethanolamine buffer. When incubated with 9.4 mM phenylglyoxal or 5.1 mM butanedione, the enzyme lost its activity with an apparent rate constant of inactivation of 0.079 min-1, respectively. The loss of enzymatic activity was concomitant with the loss of an arginine residue per active site. Phosphorylated substrates of acetate kinase, ATP, ADP and acetylphosphate as well as AMP markedly decreased the rate of inactivation by both phenylglyoxal and butanedione. Acetate neither provided any protection nor affected the protection rendered by the adenine nucleotides. However, it interfered with the protection afforded by acetylphosphate. These data suggest that an arginine residue is located at the active site of acetate kinase and is essential for its catalytic activity, probably as a binding site for the negatively charged phosphate group of the substrates. PMID- 6268171 TI - Tonin, an esteroprotease from rat submaxillary glands. AB - Tonin is an enzyme found in the rat submaxillary glands which liberates angiotensin II from angiotensinogen, the Skeggs tetradecapeptide renin substrate, and angiotensin I. Tonin hydrolyzes benzoyl-arginine ethyl ester, benzoyl arginine methyl ester, tosyl-arginine methyl ester, benzoyl-arginine p nitroanilide and other small synthetic substrates at an optimum ph of 9.0. Tonin shows, however, a great specificity with respect to angiotensin I. Tonin is inhibited by diisopropyl fluorophosphate and phenylmethylsulfonyl fluoride at high concentrations (greater than 10(-2) M) and by soybean trypsin inhibitor and aprotinin. Tonin is thus an esteroprotease of the class of the serine protease with trypsin- and chymotrypsin-like activity. Tonin belongs to the same family of enzyme as glandular kallikrein and the gamma subunit of the nerve growth factor. PMID- 6268172 TI - Regulation of neuron-specific enolase in NG108-15 hybrid cells and C6BU-1 glioma cells. AB - Distribution of three isoenzymes of brain enolase (2-phospho-D-glycerate hydro lyase, EC 4.2.1.11) (alpha alpha, alpha gamma and gamma gamma forms) in clonal cell lines of neuroblastoma (NS20Y and N18TG-2), glioma (C6BU-1), and hybrid cells NG108-15, NCB20, Nbr10A, Nbr20A, N4G-B-a and N4G-C-a) was examined with a sensitive enzyme immunoassay system, that uses a rabbit antibody to rat brain enolase alpha alpha or gamma gamma. All cell lines tested were found to possess the enolase which contains gamma subunit (a neuron-specific protein), although the alpha alpha enolase (non-neuronal enolase) was the dominant from in these cells. A clonal rat glioma (C6BU-1) cell contained about 40, 1 and 0.07 microgram/mg protein of alpha alpha, alpha gamma and gamma gamma enolases, respectively, at the confluent stage. Inclusion of 1 mM dibutyryl cyclic AMP or 10 micrometers prostaglandin E1 plus 1 mM theophylline in the culture medium of a hybrid cell (NG108-15, mouse neuroblastoma x rat glioma) resulted in a more than 2-fold increase in the concentrations of alpha gamma and gamma gamma in the cell within a few days, with little change in the alpha alpha enolase concentration. A similar increase in the concentration of gamma subunit by the nucleotide (but not by prostaglandin E1 plus theophylline) was also observed in the glioma cell (C6BU 1) line. The results suggest that the gamma subunit or the neuron-specific protein can be regulated in NG108-15 and C6BU-1 cells in a cyclic AMP-dependent fashion. PMID- 6268173 TI - Adenosine kinase from human liver. AB - Adenosine kinase (ATP: adenosine 5'-phosphotransferase, EC 2.7.1.20) has been purified to homogeneity from human liver. The yield was 55% of the initial activity with a final specific activity of 6.3 mumol/min per mg protein. The molecular weight was estimated as about 40 000 by Sephadex G-100 gel filtration and polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS). The enzyme catalyzed the phosphorylation of adenosine, deoxyadenosine, arabinoadenosine, inosine and ribavirin. The activity of deoxyadenosine phosphorylation was 18% of that of adenosine. The pH optimum profile was biphasic; a sharp pH optimum at pH 5.5 and a broad optimum at pH 7.5--8.5. The Km value for adenosine was 0.15 micrometer, and the activity was strongly inhibited at higher concentrations than 0.5 micrometer. ATP, dATP, GTP and dGTP were proved to be effective phosphate donors. Co2+ was more effective than Mg2+, and Ca2+, Mn2+, Fe2+ and Ni2+ showed about 50% of the activity for Mg2+. Some difference in structure between the adenosine kinase from human liver and that from rabbit or rat tissue, was observed by amino acid analysis and peptide mapping analysis. PMID- 6268174 TI - Partial purification and characterization of a gelatin-specific protease from the culture media of human pulmonary alveolar macrophages. AB - A gelatin-specific protease from the culture media of human pulmonary alveolar macrophages has been partial purified by gel filtration and characterized. The macrophages were obtained by bronchopulmonary lavage from the lungs of disease free smoking volunteers. The gelatin-specific protease initially requires trypsin activation. After chromatographing the culture media on a Sephadex G-200 column, trypsin is no longer required for activation. The gelatin-specific protease reported here shares many properties of previously reported gelatinases. It is inhibited by EDTA, cysteine, dithiothreitol and serum. It is unaffected by other protease inhibitors: phenylmethylsulfonyl fluoride, tosyllysine chloromethyl ketone and p-chloromercuribenzoate. Of all substrates tested activity was observed only with gelatin. It was inactive toward collagen, elastin and methemoglobin. This enzyme may have a role in the digestion of collagen which has been cleaved by a mammalian collagenase. PMID- 6268175 TI - Purification of a Ca2+-activated protease from rat erythrocytes and its possible effect on pyruvate kinase in vivo. AB - A Ca2+-activated protease with [32P]phosphopyruvate kinase as substrate was purified to about 50% from rat erythrocytes. The purification involved chromatography on Sepharose/Sephadex gels, DEAE-cellulose and (NH4)2SO4 precipitation. The protease required 3.3 mM Ca2+ for full activity. When pyruvate kinase (ATP: pyruvate 2-O-phosphotransferase, EC 2.7.1.40) was purified from erythrocytes incubated with [32P]phosphate it contained 0.5 mol [32P]phosphate/mol enzyme subunit. When 3.3 mM Ca2+ were added at hemolysis this incorporation decreased. The possible importance of this Ca2+-activated protease for the regulation of pyruvate kinase in erythrocytes is discussed. PMID- 6268176 TI - Mechanism of activation of glucocerebrosidase by co-beta-glucosidase (glucosidase activator protein). AB - The nature of the stimulatory action of the protein 'coglucosidase' on glucocerebrosidase was investigated with the use of highly purified cofactor from bovine spleen, radioactive glucosyl ceramide and methylumbelliferyl-beta glucoside. A complex between glucosidase and either substrate could not be detected under equilibrium and non-equilibrium binding conditions. Complex formation between stimulating protein and the enzyme could be shown by the binding of the enzyme to an affinity column containing coglucosidase. This binding could be blocked by adding phosphatidylserine to the enzyme. The lipid also stimulated the enzyme. Additional evidence for binding of the enzyme to the two kinds of stimulators was the finding that they protected the enzyme against inactivation by N-ethylmaleimide and chloromercuriphenylsulfonate. A role for lipids in the stimulatory action of coglucosidase was shown by extracting lipids from the enzyme; this resulted in a loss of basal enzyme activity and of sensitivity to activation by the protein. Adding back to the lipids or phosphatidylserine increased the sensitivity of the delipidated enzyme to coglucosidase. Using the crude, unextracted enzyme we could show that low concentrations of phosphatidylserine augmented the effectiveness of coglucosidase but high concentrations of the lipid blocked the effect of the protein. It is proposed that lipids, particularly acidic ones, act on solubilized glucocerebrosidase to produce an enzyme conformation which allows binding and stimulation by coglucosidase. At higher lipid concentrations, the acidic lipids bind, in competition with coglucosidase, to the latter's binding site on the enzyme. PMID- 6268177 TI - High density lipoprotein utilization by dispersed rat luteal cells. AB - Utilization of lipoproteins by cells prepared by collagenase dispersion of ovaries of immature gonadotropin-primed rats was studied. Human and rat HDL increased basal progestin secretion and incorporation of [14C]oleate into cellular sterol esters 2-fold during a 2 h incubation, with maximal stimulation occurring at a lipoprotein sterol concentration of 125 micrograms/ml. This concentration of HDL cholesterol also increased progestin production by cells stimulated with dibutyryl cyclic AMP. Human LDL or cholesterol-rich lipid dispersions had little effect upon either progestin secretion or sterol esterification at similar sterol concentrations. However, addition of delipidated human HDL apolipoproteins to the cholesterol-rich lipid dispersions markedly enhanced progestin production. Incubation of the dispersed cells in the presence of 25 micro M ML-236B, which blocked cellular de novo sterol synthesis by over 90%, had no effect upon progestin secretion. Specific uptake of human 125I labeled HDL by the dispersed cells was observed. Analysis fo 125I-labeled HDL uptake as a function of lipoprotein concentration indicated that the uptake process was saturated at HDL levels of 200-400 micrograms protein/ml. The amount of HDL specifically associated with the cells at saturating levels after 1 h of incubation was sufficient to account for the increased progestin synthesis and sterol ester storage observed during this time. During the incubations cell specific degradation of the 125I-labeled HDL apolipoprotein appeared to be minimal. We conclude that lipoprotein-carried cholesterol is an important substrate for rat luteal cells and that these cells possess a specific mechanism for the uptake of HDL. PMID- 6268178 TI - Conformational changes of the subunits C1q, C1r and C1s of human complement component C1 demonstrated by 125I labeling. AB - C1s and C1r proenzymes and enzymes (C1s, C1r) and C1q were labeled with 125I. The distribution of the 125I label between H- and L-chain of C1s was only slightly dependent on the state of activation of C1s, and approx. 90% of the label was found in the H-chain. In the C1r proenzyme molecules 50% of the label was incorporated into the H-chain. The C1r H-chain label was reduced to 10% on activation of C1r to C1r, while the L-chain label increased to 90% of the total label. The presence of either C1s, C1q or C1qs during labeling reduced the C1r H chain level, although C1r remained in the proenzyme form. The presence of C1s or C1rs enhanced the 125I uptake of C1q in Ca2+ or EDTA medium. This was unexpected because one would have anticipated a diminution of the C1q label due to the apposition of C1r and C1s, similarly as it occurs during C1rs complex and C1s dimer formation for the H-chain label of C1s. The results show that C1r and C1q alter their conformation during activation and C1 complex formation. PMID- 6268179 TI - Purification and characterisation of the cyclic AMP-dependent protein kinase, the C- and the R-protein from bovine liver. AB - A cyclic AMP-dependent protein kinase, its regulatory (R) and catalytic (C) protein were isolated from bovine liver, The cyclic AMP-dependent protein kinase showed two protein bands on SDS-polyacrylamide gel electrophoresis with molecular weights of 54 000 and 40 000. They correspond to the data for the separately isolated R-and C-protein. The molecular weight of the holoenzyme ranged from 172 000-179 000, depending on the estimation method. The molecular weight of the R protein ranged from 97 000-98 000. This, and the results of the SDS polyacrylamide gel electrophoresis, demonstrates a dimeric structure. The frictional ratios (f/fo) of 1.67-1.7 for the holoenzyme and 1.9 for the R-protein correspond to highly asymmetric shapes. Assuming a prolate form, the axial ratios are 13-14 and 17, respectively. The C-protein is globular (f/fo 1.1-1.26, axial ratio 3-5). The secondary structure with 35% alpha-helix, 19% beta-sheet and 49% aperiodic form of the holoenzyme is similar to the R-protein with 35, 19 and 46%, respectively. The C-protein contains 29% alpha-helix, 21% beta-sheet and 50% aperiodic form. The dimeric R-protein binds 4 mol cyclic AMP and can be phosphorylated in the presence of the C-protein. An absorption coefficient, A280nm 1.0%, of 5.4 was calculated for the R-protein and of 13.6 for C-protein. The data for C-protein, e.g., molecular weight, heterogeneity in isoelectrofocusing, phosphate content, etc., are in good agreement with those found by Sudgen, P.H. and Corbin, J.D. (1976) biochem. J. 159, 423-437. PMID- 6268180 TI - EPR spectral changes of nitrosyl hemes and their relation to the hemoglobin T-R transition. AB - EPR spectra of nitrosyl hemes were used to study the quaternary structure of hemoglobin. Human adult hemoglobin has been titrated with nitric oxide at pH 7.0 and 25 degrees C. After the equilibration of NO among the alpha and beta subunits the samples were frozen for EPR measurements. The spectra were fitted by linear combinations of three standard signals: the first arising from NO-beta-hemes and the other two arising for NO-alpha-hemes of molecules in the high- and low affinity conformations. The fractional amounts of alpha subunits exhibiting the high-affinity spectrum fitted the two-state model (Edelstein, S.J. (1974) Biochemistry 13, 4998-5002) with the allosteric constant L = 7.10(6) and relative affinities cNO alpha and cNO beta approx. 0.01. Hemoglobin has been marked with nitric oxide one chain using low-saturation amounts of nitric oxide. The EPR spectra was studied as a function of oxygen saturation. Linear combinations of the three standard signals above fitted these spectra. The fractions of molecules exhibiting the high-affinity spectrum fitted the two-state model with L = 7 . 10(6), c)2 = 0.0033 and cNO alpha = 0.08, instead of cNO alpha = 0.01. Thus, the two-state model is not adequate to describe the conformational transition of these hybrids. The results present evidence of the non-equivalence between oxygen and nitric oxide as ligands. PMID- 6268181 TI - The three-iron cluster in a ferredoxin from Desulphovibrio gigas. A low temperature magnetic circular dichroism study. AB - Ferredoxin II from Desulphovibrio gigas is a tetrameric protein containing a novel iron-sulphur cluster consisting of three iron atoms. The low-temperature magnetic circular dichroism (MCD) spectra of the oxidized and dithionite-reduced forms of ferredoxin II have been measured over the wavelength range approx. 300 800 nm. Both oxidation levels of the cluster are shown to be paramagnetic, although only the oxidized form gives an EPR signal. MCD magnetization curves have been constructed over the temperature range approx. 1.5-150 K and at fields between 0 and 5.1 Tesla. The curve for the oxidized protein can be fitted to a ground state of spin S = 1/2 with an isotropic g factor of 2.01. There is evidence for the thermal population of a low-lying electronic state above 50 K. The reduced protein gives a distinctive set of magnetization curves that are tentatively assigned to a ground state of S = 2, with a predominantly axial zero field distortion that leaves the doublet Ms = +/-2 lowest in energy. The zero field components have a maximum energy spread of approx. 15 cm-1. which places an upper limit of 4 cm-1 on the axial zero-field parameter D. The MCD spectra of the oxidized and reduced forms of the cluster are quite distinctive from one another. The spectra of the oxidized state are also different from those of oxidized high potential iron protein from Chromatium and should provide a useful criterion for distinguishing between four- and three-iron clusters in their highest oxidation levels. PMID- 6268182 TI - Effect of highly purified porcine gut glucagon-like immunoreactivity (glicentin) on glucose release from isolated rat hepatocytes. AB - We studied the effect of the highly purified gut peptide glicentin on the glucose production and cyclic AMP accumulation of isolated rat hepatocytes. Glicentin at 2.10(-7) mol/l had the same effect on glucose production as maximally effective concentrations of glucagon, but did not stimulate cyclic AMP to the same extent; furthermore, glicentin apparently had only 1/100 of the potency of glucagon on glucose production. During incubation with hepatocytes glicentin was degraded to low molecular weight fragments one of which were chromatographically very similar to fragments of glucagon. It is suggested that glicentin exerts its glucagon-like effects on hepatocytes only after degradation to glucagon-like fragments. The results also demonstrate that the coupling between cyclic AMP accumulation and glucose production depends on the nature of the stimulatory peptide. PMID- 6268183 TI - Activation of phosphodiesterase in frog rod outer segment by an intermediate of rhodopsin photolysis I. AB - Guanosine 3',5'-cyclic monophosphate phosphodiesterase (EC 3.1.4.1) in frog rod outer segment prepared by a sucrose stepwise density gradient method was activated by light in the presence of GTP. Rhodopsin in rod outer segment was solubilized with sucrose laurylmonoester and then purified by concanavalin A Sepharose column. Addition of photo-bleached preparation of the purified rhodopsin to the crude rod outer segment, which had been prepared by 43% (w/w) sucrose floatation, caused the activation of phosphodiesterase in the dark, while each component of the photo-product eluted from the column (all-trans retinal and opsin) did not. Regenerated rhodopsin prepared from 11-cis retinal and purified opsin activated phosphodiesterase when it was bleached. From these facts it is suggested that an intermediate or a process of photolysis of rhodopsin causes activation of phosphodiesterase. PMID- 6268184 TI - Activation of phosphodiesterase in frog rod outer segment by an intermediate of rhodopsin photolysis. II. AB - Frog (Rana catesbeiana) rod outer segment membrane contains cyclic GMP phosphodiesterase (EC 3.1.4.1). Irradiation of dark-adapted rod outer segment membrane increased the enzyme activity by 5-20-fold in the presence of GTP. The phosphodiesterase in rod outer segment membrane is also activated by mixing a photo-product of 11-cis (regenerated), 9-cis or 7-cis rhodopsin which is stable at 0 degrees C. However, neither opsin in the membrane nor all-trans retinal activates the enzyme. The phosphodiesterase in rod outer segment membrane is also activated by irradiation at -4 degrees C. Thus, we conclude that the phosphodiesterase in activated by a common photolysis intermediate of these rhodopsin isomers, perhaps before metarhodopsin II decays. PMID- 6268186 TI - Histone phosphorylation in phorbol ester stimulated and beta-adrenergically stimulated mouse epidermis in vivo and characterization of an epidermal protein phosphorylation system. AB - Under certain physiological conditions a change in the phosphorylation of histones in mouse epidermis in vivo was observed. Thus a single local application of the tumor-promoting mitogen 12-O-tetradecanoylphorbol-13-acetate caused a long lasting increase of histone H1 phosphorylation which paralleled stimulated cell proliferation. Injection of the antimitotic beta-adrenergic agonist isoproterenol led to a temporary decrease in the rate of phosphorylation of H1, H2A and H2B immediately after cyclic AMP accumulation. A complete protein phosphorylation system could be demonstrated in mouse epidermis homogenates. The following enzyme activities were partially purified and characterized: a cyclic AMP-dependent histone kinase; a 'casein kinase' and an 'unspecific' protein kinase; a histone specific protein phosphatase; and two 'unspecific' phosphoprotein phosphatases. In addition, a stimulatory effect of cyclic GMP on histone phosphorylation was observed. The enzymes were found to be predominantly localized in the 105000 X g supernatant, but a small proportion of protein kinase and phosphatase activity could be regularly demonstrated in cell nuclei. PMID- 6268185 TI - Interaction of guanine nucleotides with adenylate cyclase in normal and spontaneously transformed RL-RP-C cloned rat hepatocytes. AB - Spontaneous transformation of RL-PR-C hepatocytes leads to alterations in the adenylate cyclase complex which include a lower than normal basal level of activity, a loss of sensitivity to exogenous GTP, and a decreased sensitivity to isoproterenol. Both normal and transformed membranes possess substantial GTPase activity. Treatment of transformed hepatocyte membranes with either isoproterenol plus GMP or with cholera toxin, under conditions that displace tightly bound GDP, restored the GTP effect on adenylate cyclase, and eliminated the lag in the activation by guanyl-5'-yl-imidodiphosphate. Such pretreatment also enhanced guanine nucleotide effects on the adenylate cyclase of normal hepatocytes. These results are explainable on the basis that transformation increases adenylate cyclase-associated GTPase activity, and increases occupancy of nucleotide regulatory sites by inactive or inhibitory guanine nucleotides, e.g., GDP. Seemingly, both catecholamines and cholera toxin promote an exchange reaction at the regulatory sites, resulting in clearance of these sites of inhibitory nucleotides. PMID- 6268187 TI - Regulation by a beta-adrenergic receptor of a Ca2+-independent adenosine 3',5' (cyclic)monophosphate phosphodiesterase in C6 glioma cells. AB - The hormonal control of cyclic nucleotide phosphodiesterase (EC 3.1.4.17) activity has been studied by using as a model the isoproterenol stimulation of cyclic AMP phosphodiesterase activity in C6 glioma cells. A 2-fold increase in cyclic AMP phosphodiesterase specific activity was observed in homogenates of isoproterenol-treated cells relative to control. This increase reached a maximum 3 h after addition of isoproterenol, was selective for cyclic AMP hydrolysis, was reproduced by incubation with 8-Br cycl AMP but not with 8-Br cyclic GMP and was limited to the soluble enzyme activity. The presence of 0.1 mM EGTA did not alter the magnitude of the increase in phosphodiesterase activity. Moreover, the calmodulin content in the cell extracts was not changed after isoproterenol. DEAE Sephacel chromatography of the 100000 X g supernatant resolved two peaks of phosphodiesterase activity. The first peak hydrolyzed both cyclic nucleotides and was activated by Ca2+ an purified calmodulin. The second peak was specific for cyclic AMP but it was Ca2+- and calmodulin-insensitive. Isoproterenol selectively increased the specific activity of the second peak. Kinetic analysis of the cyclic AMP hydrolysis by the induced enzyme revealed a non-linear Hofstee plot with apparent Km values of 2-5 microM. Cyclic GMP was not hydrolyzed by this enzyme in the absence or presence of calmodulin and failed to affect the kinetics of the hydrolysis of cyclic AMP. Gel filtration chromatography of the induced DEAE-Sephacel peak resolved a single peak of enzyme activity with an apparent molecular weight of 54000. PMID- 6268188 TI - Gluconeogenesis in rabbit liver. IV. The effects of glucagon, epinephrine, alpha- and beta-adrenergic agents on gluconeogenesis and pyruvate kinase in hepatocytes given dihydroxyacetone or fructose. AB - 1. Epinephrine, isoproterenol and phenylephrine each increases significantly gluconeogenesis (from dihydroxy-acetone or D-fructose) and glycogenolysis when added to hepatocytes from 48-h fasted rabbits. Such stimulation of both processes by epinephrine, isoproterenol or phenylephrine is negated by the beta-adrenergic antagonist propranolol but remains significant in the presence of the alpha adrenergic antagonist phentolamine. Conversely, previous data suggest that catecholamine-induced stimulation of glucose formation from L-lactate is both alpha- and beta-adrenergic-sensitive. 2. Glucagon, epinephrine, isoproterenol, phenylephrine and dibutyryl cyclic AMP each inhibits significantly pyruvate kinase activity in rabbit hepatocytes. Inhibition of pyruvate kinase activity by epinephrine, isoproterenol or phenylephrine is negated by propranolol but insensitive to phentolamine. 3. These observations suggest that enhancement by epinephrine of glucose formation from either dihydroxyacetone or D-fructose is solely beta-adrenergic-regulated, just as is its inhibition of pyruvate kinase activity. Stimulation of gluconeogenesis by glucagon, epinephrine, isoproterenol, phenylephrine or dibutyryl cyclic AMP may be at least in part directly related to their ability to inhibit pyruvate kinase. PMID- 6268189 TI - Adenosine 3',5'-monophosphate receptor proteins in HeLa cells. AB - The adenosine 3',5'-monophosphate receptor proteins of HeLa cells have been characterized. Using the Millipore filter assay, in the presence of 5'AMP and a phosphodiesterase inhibitor, specific [3H]cyclic AMP binding was detected in cytosol and in a nuclear-free particulate fraction, but not in nuclei. Both preparations exhibited biphasic Scatchard plots. 8-Azido[32P]cyclic AMP was used as a photoaffinity probe to covalently link ligand with receptor proteins. Proteins were then separated on denaturing gels and analyzed by autoradiography. The cytosol exhibited four specific binding proteins, with molecular weights of 46 000, 50 000, 52 000 and approx. 120 000. The 50 000/52 000 doublet could not be interconverted by phosphorylation-dephosphorylation reactions. On DEAE cellulose, the 50 000-dalton protein eluted with peak II cyclic AMP-dependent protein kinase. The other proteins eluted with Peak I and with a binding peak not associated with kinase activity. Only the 50 000 protein was precipitated by type II protein kinase antibody from bovine heart. In the particulate fraction, the 120 000 protein was not detectable, but 8-azido[32P]cyclic AMP treatment revealed the other three proteins, with a relative increase in the 50 000-dalton protein. The results suggest that HeLa cells have four binding proteins which can associate with catalytic subunit and that the Peak I enzyme is heterogeneous, consisting of several distinct regulatory subunits. PMID- 6268190 TI - Characterization of the desensitized state of Leydig tumor cells. AB - A perifusion system has been used to study the in vitro desensitization of isolated Leydig tumor cells. It was observed that the cells become refractory, as measured by decreased rates of steroidogenesis, during continuous perifusions with saturating concentrations of either human choriogonadotropin (CG), cholera toxin, or 8-bromo-cyclic AMP. Furthermore, an initial perifusion of the cells with either human CG, cholera toxin, or 8-bromo-cyclic AMP causes subsequent desensitization towards all three stimuli. Thus, each of these stimuli is equally effective in inducing a state of desensitization in these cells that is manifested by a steroidogenic lesion(s) distal to cyclic AMP formation. It was found that the post-cyclic AMP lesion(s) in the desensitized state occurs prior to the formation of pregnenolone. However, the decreased rates of steroidogenesis do not seem to arise from a depletion of intracellular cholesterol. PMID- 6268191 TI - Effect of methionine deprivation on S-adenosylmethionine decarboxylase of tumour cells. AB - Transference of Walker carcinoma and TLX5 lymphoma from normal L-methionine containing medium to medium containing limiting amounts of L-methionine, or L homocysteine only, caused a 2-fold increase of S-adenosylmethionine decarboxylase activity. Kinetic analysis showed an increase in the V value of the enzyme from 22 to 53 pmol/min per mg protein in media containing only 0.1 mM L-homocysteine, without any alteration in the Km value (0.1 mM). The increase in enzyme activity does not result from (a) a reduction of the intracellular level of S adenosylmethionine, since cycloleucine, an inhibitor of methionine adenosyltransferase, had no effect on enzyme activity; (b) an increase in intracellular adenosine 3',5' monophosphate (cyclic AMP), since high extracellular concentrations of N6-monobutyryl cyclic AMP had no effect on enzyme activity; (c) an alteration of polyamine levels, since addition of micromolar concentrations of exogenous putrescine, spermidine and spermine did not prevent the induction of S-adenosylmethionine decarboxylase activity in methionine-free media containing 0.1 mM L-homocysteine. The increased enzyme activity appears to be mainly due to enhanced stabilization, since the half-life was increased from 2.45 to 5.0 h in media containing only 0.1 mM L-homocysteine. Induction of enzyme activity is specific to the removal of L-methionine, since no increase occurred in the absence of L-serine or L-glycine, or both, or by reduction of the serum concentrations in the medium. PMID- 6268192 TI - Binding of cyclic AMP and cyclic GMP to renal cortical homogenates. Relationship with phosphorylation. AB - This study examined the binding of both cyclic AMP and cyclic GMP to receptor proteins in particulate and soluble subfractions of renal cortical homogenates from the golden hamster. The binding of both nucleotides was compared to subsequent effects of both nucleotides on the phosphorylation of histone from identical fractions. Cyclic AMP binding and cyclic AMP-dependent protein kinase activity predominated in the cytosol, with some binding and enzyme activity also detected in particulate fractions. Cyclic GMP and cyclic GMP-dependent protein kinase activity could only be demonstrated in cytosolic fractions and represented only 20-30% of cyclic AMP-dependent activity in this fraction. Binding of both nucleotides was highly specific, however, cyclic AMP showed some interaction with cyclic GMP binding. Evidence suggesting that each nucleotide interacts with a specific protein kinase was as follows: both the binding activity of the cyclic nucleotides and their combined protein kinase activity show additivity; cyclic AMP and cyclic GMP binding activity could be separated on sucrose gradients; cyclic AMP and cyclic GMP protein kinase activity could be separated with Sephadex G-100 chromatography, after preincubation of homogenate supernatants with either cyclic AMP or cyclic GMP. The results demonstrate the presence of both cyclic AMP- and cyclic GMP-dependent protein kinase in renal cortex. PMID- 6268193 TI - Aminopyrine uptake by guinea pig gastric mucosal cells. Mediation by cyclic AMP and interactions among secretagogues. AB - The role of cyclic nucleotides in regulating acid secretion by dispersed mucosal cells from guinea-pig stomach was examined by measuring first the ability of histamine and carbachol to stimulate [dimethylamine-14C]aminopyrine uptake and cyclic nucleotide metabolism and secondly, the effect of exogenous cyclic nucleotides on basal and stimulated [14C]aminopyrine uptake. The [14C]aminopyrine was found in an acidic, osmotically sensitive compartment, probably associated with the initial steps in acid secretion by these cells. Although histamine increased [14C]aminopyrine uptake and cyclic AMP synthesis as expected, histamine was approx. 10-fold more potent in inducing [14C]aminopyrine uptake. This dissociation of [14C]aminopyrine uptake and cyclic AMP metabolism process was further manifested by the observation that prostaglandin E1 failed to increase [14C]aminopyrine uptake, although it did cause a rise in cellular cyclic AMP. Furthermore, prostaglandin E1 did not alter the [14C]-aminopyrine uptake caused by histamine. Carbachol was found to increase the [14C]aminopyrine uptake and also to potentiate the ability of histamine to increase [14C]aminopyrine uptake. Carbachol, however, affected neither the histamine-induced increase in cyclic AMP nor the binding of [3H]histamine to the cells. Cimetidine, a histamine H2 receptor antagonist, blocked the [14C]aminopyrine uptake induced either by histamine alone or by the potentiating combination of histamine plus carbachol. These results suggest that cyclic AMP is mediating the action of histamine on [14C]aminopyrine uptake but changes in cyclic AMP per se are not necessarily the cause for the potentiated increase in [14C]aminopyrine uptake. Furthermore, the potentiated response observed with histamine plus carbachol on [14C]aminopyrine uptake occurs at a biochemical step distal to and not obviously related to cyclic AMP generation. PMID- 6268194 TI - A Zn2+ binding constituent of fababeans. AB - Binding of Zn2+ by an aqueous extract of fababeans was estimated spectrophotometrically. Treatment of the extract with phytase removed virtually all of the phytate and about 82% of the Zn2+ binding. Gel permeation chromatography of the extract showed that the Zn2+ binding factor eluted at the same volume as phytate. The major Zn2+ binding constituent of the bean extract appears to be phytate. PMID- 6268195 TI - [Separation of fractions of phosphoprotein phosphatase and its protein inhibitors by isoelectrofocusing]. AB - Individual molecular forms of phosphoprotein phosphatase from albino rat cardiac muscle were separated by isoelectrofocusing, resulting in a few fractions differing in pI (5.1, 5.4, 5.9-6.1 (double peak) and 7.1, respectively). Isoelectrofocusing of a purified enzyme preparation also allowed to isolate and characterize two protein inhibitors of the enzyme. The first one with pH 6.5-6.7 is similar to the thermostable phosphoprotein phosphatase inhibitor known from literature. This protein inhibits the enzyme activity by 90%; its effect is not decreased after 5-min heating at 95 degrees. The other inhibitor protein with pH 5.6-5.8 is thermolabile. When the enzyme activity was decreased 2.5-fold prior to thermal treatment, the latter protein lost this ability after heating at 95 degrees and inhibited the enzyme only by 9%. It is assumed that inhibitory proteins beside low molecular weight effectors can be involved in the mechanisms of the post-synthetical operative modification of phosphoprotein phosphatase function. PMID- 6268196 TI - [Properties of phosphodiesterase from Vipera lebetina venom immobilized on Agarose]. AB - Preparations of phosphodiesterase from Vipera lebetina venom immobilized on agarose were obtained. The kinetic properties for the hydrolyses of various substrates of soluble and immobilized phosphodiesterase, e. g. effects of pH, temperature, substrate concentrations, etc., were compared. The values of Km, V and activation energy for the substrate hydrolyses were determined. PMID- 6268197 TI - [Specific effect of endonucleases from Brevibacterium ammoniagenes on DNA]. AB - The previously described deoxyribonucleases from Brevibacterium ammoniagenes have been characterized. It was shown that they are endonucleases with molecular weights of 60 000 (I), 10 000 (II) and 20 000 (III). The rate of endonuclease I effect on native DNA exceeded that on the denatured DNA 2-fold. The mechanism of its action is of a single hit type. The enzyme hydrolyzes two chains of DNA simultaneously in two symmetrical sites and splits the bond 5'-P to form fragments with terminal 5'-OH and 3'-P. Endonuclease I was characterized as deoxyribonucleate-3'-oligonucleotide hydrolase (EC 3.1.4.6). PMID- 6268198 TI - [Role of hydrophobic interactions and functional groups in the inhibitor binding to various sites of mitochondrial succinate-cytochrome c reductase]. AB - It was shown that the efficiency of succinate-cytochrome c reductase inhibitors, i. e. neutral polar substances, negatively charged phenols and 2-hydroxy-3-alkyl 1.4-naphthoquinones, is increased with an increase in their hydrophobicity. Plotting-lg C50 versus lg P for all the three groups of inhibitors, the role of functional groups of the inhibitors in their binding to the corresponding sites of the respiratory chain was determined. The efficiency of inhibition by neutral polar substances does not depend on the chemical nature of the inhibitors and is described by the equation-lg C50 = 0.864 lg P + 0.222 (r = 0.99). The negatively charged group of dissociated phenols determines the specificity of the inhibitor binding to the terminal site of the succinate dehydrogenase complex and is involved in the inhibitor binding to the enzyme. The carbonyl group of 2-hydroxy 3-alkyl-1.4-naphthoquinones selectively increases the affinity and efficiency of binding of these inhibitors to the b-c1 site of the respiratory chain. PMID- 6268199 TI - [Dependence of the anticodon stem conformation of tRNA Trp on the anticodon loop structure]. AB - After conversion of the exposed cytosine bases of the anticodon loop into uridines with bisulfite the pattern of hydrolysis of the tRNATrp anticodon stem under the action of cobra venom endonuclease is altered. A removal of the 3'-CCA end has no influence on the hydrolytic pattern of the anticodon stem in tRNATrp. Thus, the nucleotide sequence of the anticodon loop influences the conformation of the neighbouring stem. PMID- 6268200 TI - [Na,K-ATPase from duck salt glands]. AB - The protein and lipid composition of Na,K-ATPase from duck salt glands were characterized. A kinetic analysis of hydrolysis of two substrates, one of which (ATP) provides and the other (ITP) does not provide for cation active transport was carried out. In both cases two Km values were obtained and were found equal to 10 and 330 microM for ATP and 35 and 710 microM for ITP, respectively. This suggests the existence of substrate sites with high and low affinities. The Hill coefficient for the ATP hydrolysis was equal to 1.4-1.6; the ITP hydrolysis was non-cooperative. It was assumed that positive cooperative interactions between Na,K-ATPase protomers are necessary for active translocation of Na+ and K+. PMID- 6268201 TI - [DNA-methylase from Arthrobacter luteus screens DNA from the action of site specific endonuclease Alu I]. AB - DNA-methylase was isolated from a cell extract of A. luteus and partially purified by chromatography on phosphocellulose. The purified enzyme methylates DNA of phage lambda and plasmids pBr322, thus making them resistant to a subsequent action of endonuclease Alu I. It has been shown that cytosine is the object of methylation within DNA. This modification does not screen DNA from the action of site-specific endonucleases Sal I, Bam HI, EcoR I, EcoR II, Xho I and Xho II. It has been experimentally demonstrated that the isolated methylase is site-specific and identifies in the DNA the nucleotide sequence 5'-AGCT-3', by methylating cytosine in the DNA. PMID- 6268202 TI - [3-oxosteroid-delta'-dehydrogenase adsorption from Mycobacterium rubrum on silica gel modified with phospholipids as a model of enzyme interaction with biomembranes]. PMID- 6268203 TI - Metabolism of glucose by Sertoli cells in culture. PMID- 6268204 TI - GnRH-receptor interaction. V. Down-regulation of pituitary receptors for GnRH in ovariectomized ewes by infusion of homologous hormone. PMID- 6268205 TI - Control of Sertoli cell response to FSH: regulation by homologous hormone exposure. PMID- 6268206 TI - Evidence against an obligatory role for catecholamine release or prostacyclin synthesis in the effects of relaxin on the rat uterus. PMID- 6268207 TI - Mineralogical alterations in osteoporotic bone tissue structure. PMID- 6268208 TI - Comparative histocompatibility testing of seven calcium phosphate ceramics. AB - Five hydroxyapatite and two tricalcium phosphate ceramics were implanted in rat femora for one to six months. They were compared with each other in regard to biocompatibility and bone induction. After one month bone had grown directly on to the surface of all implants. After six months the on-growth of bone had increased with the exception of two dense HA materials. In these materials some bio-degradation had occurred with subsequent formation of a wide macrophage interlayer. Bio-degradation and biocompatibility of calcium phosphate ceramics seem to depend not only on density but also on other factors. Induction of bone could not be observed in soft tissue environment. PMID- 6268209 TI - Hydroxyapatite reinforced polyethylene--a mechanically compatible implant material for bone replacement. PMID- 6268210 TI - Modified protein kinase activity and isozyme distribution in adenocarcinoma of the human colon. AB - Protein kinase activity and histone kinase isozyme distribution have been determined in soluble extracts of adenocarcinoma of the human colon and compared to adjacent normal mucosa. The results show an enhancement in endogenous protein kinase activity and the presence of an additional isozyme (PKI) for histone kinase activity in the tumour tissue. PKI activity exhibited a peculiar behaviour in comparison to the isozyme. PKII present in both carcinoma and normal mucosa after dialysis of the soluble extracts. It is suggested that alteration of intracellular regulatory processes involved in PKI activity might be related to the maintenance of the proliferate state in human colon carcinoma. PMID- 6268211 TI - Changes in the protonation state of bacterio-opsin during reconstitution of bacteriorhodopsin. AB - Protonation changes of the protein occur during the reconstitution of bacteriorhodopsin from bacterio-opsin and all-trans retinal in the purple membrane of Halobacterium halobium. The protonation changes are conveniently determined from measures of the pH changes after photoisomerisation of 9-cis retinal in apomembrane preparations, which induces the reconstitution. In addition, to the omega-amino group of the lysine which is involved in the condensation of retinal and bacterio-opsin, the dissociation equilibria of at least two other amino acid residues are changed during the reconstitution. The results are consistent with a proposed model of chromophore structure in which an interaction of the Schiff's base occurs with two protonable amino acid residues. PMID- 6268212 TI - Size and frequency of gaps in newly synthesized DNA of xeroderma pigmentosum human cells irradiated with ultraviolet light. AB - Native newly synthesized DNA from human cells (xeroderma pigmentosum type) irradiated with ultraviolet light releases short pieces of DNA (L-DNA) when incubated with the single-strand specific S1 nuclease. This is not observed in the case of unirradiated cells. Previous experiments had shown that the L-DNA resulted from the action of S1 nuclease upon gaps, i.e., single-stranded DNA discontinuities in larger pieces of double-stranded DNA. We verified that the duplex L-DNA, that arises from the inter-gap regions upon S1 nuclease treatment, has a size which approximates the distance between two pyrimidine dimers on the same strand; this has been observed at different fluences of ultraviolet-light and indicates that the gap is related to or opposite the dimer. A method was devised to measure the size of the gaps. A Poisson distribution analysis of the percentage of the L-DNA produced as a function of S1 nuclease concentration made this possible. 65% of the gaps corresponded to stretches of 1,250 nucleotides and 35% to stretches of 150 nucleotides. These parameters have been considered in the proposition of a model for DNA synthesis on a template containing pyrimidine dimers. PMID- 6268213 TI - Interpreting power spectra from nonstationary membrane current fluctuations. AB - It is often desirable to characterize membrane current fluctuations from ionic channels under conditions in which the mean current and the variance of the fluctuations change with time. A simple theory is developed that relates the power spectrum to the channel characteristics under such nonstationary conditions, assuming that the mean current time-course has been removed from the fluctuation records. Strategies for removing the mean time-course are discussed, the spectra are calculated from simulated channel fluctuations for comparison with the theory. PMID- 6268214 TI - Intracellular pH and ionic channels in the Loligo vulgaris giant axon. AB - Squid giant axons were used to investigate the reversible effects of intracellular pH(pHi) on the kinetic properties of ionic channels. The pharmacologically separated K+ and Na+ currents were measured under: (a) internal perfusion, (b) enzymatic Pronase treatment, and (c) continuous estimate of periaxonal ion accumulation. Variation of internal pH from 4.8 to 11 resulted in: (a) a decrease of steady-state sodium inactivation at positive potentials similar to the effect of the proteolytic enzyme Pronase, (b) a shift of the h infinity (E) curve toward depolarizing voltages, and (c) a decrease of the time constant of inactivation for potentials below -20 mV (an increase above). A plot of the steady-state sodium conductance at E = +40 mV as a function of pHi suggests that two groups with pKa 10.4 and 5.6 affect respectively the inactivation gate and the rate constants for the transition from the inactivated to the second open state (h2) (Chandler and Meves, 1970b). The voltage shifts of the kinetic parameters predicted by the Gouy-Chapman-Stern theory are well satisfied at high pHi and less at low. Once corrected for voltage shifts, the forward rate constants for channel opening were found to be slowed with the acidity of the internal or external solution. PMID- 6268215 TI - Hemoglobin-carbon monoxide binding rate. Low temperature magneto-optical detection of spin-tunneling. AB - The spin-tunneling model of Hb--CO binding is used to calculate the binding rate at low temperature and high magnetic fields. The rate is calculated in second order perturbation theory assuming that spin-orbit coupling mediates the Hb iron electronic state change. The reaction which occurs at the crossing of the S = 2 and S = 0 energy vs. configuration coordinate curves is nonadiabatic, having a small electronic transition matrix element. Since detection of CO binding by polarized light in the Soret band makes it possible to observe hemes at specific orientation to the field direction, the rate is calculated for arbitrary heme orientation. Comparison with measurements at low temperature in zero field is made for spin quantization along the molecular crystal field direction. PMID- 6268216 TI - Gating currents in th intact crayfish giant axon. AB - Both single-sweep and signal-averaged asymmetry current are measured from intact crayfish axons after ionic currents are blocked with tetrodotoxin and 4 aminopyridine. The ON asymmetry charge saturates at about 0 mV and no ON charge movement is detectable at voltages negative to -140 mV. The areas of ON and OFF asymmetry charge are equal for short depolarizations but the ratio QOFF/QON decreases for longer depolarizing pulses. Sodium and asymmetry current magnitudes can be changed in parallel by lowering the hold potential or by imposing conditioning prepulses. Our results are consistent with the concept that asymmetry current in generated by movement of trapped charge in association with Na channel gating. PMID- 6268219 TI - Light-induced changes of cyclic GMP content in frog retinal rod outer segments measured with rapid freezing and microdissection. AB - Cyclic GMP concentration was measured in the rod outer segments (ROS) of the isolated frog retinas. Retinas were quickly frozen in 0.5 s after the short light flash producing 90%-saturated late receptor potential (2,000 rhodopsins bleached per rod). ROS were obtained by microdissection, the cGMP levels were determined by radioimmunoassay method. No detectable changes in cGMP concentration was found in this stimulus condition. Dark-adapted ROS contained 46.3 +/- 2 pmol/mg. 3-s bright illumination (ca. 10(7) rhodopsins bleached per rod per second) led to approximately 30% drop in cGMP content. It is supposed that the main part of cGMP with the ROS is in the bound state and therefore fast light-induced changes in its minor free fraction may escape the detection. PMID- 6268218 TI - Novel kinetics in the sodium conductance system predicted by the aggregation model of channel gating. AB - Special voltage-clamp pulse protocols are given that make differential predictions for the kinetics of models based on a simple sequential, simple cyclic, and an aggregation scheme. Detailed kinetic time-courses for the discriminating pulse protocols are numerically derived from the differential equation system that describes the aggregation model. PMID- 6268217 TI - Sodium channel inactivation in the crayfish giant axon. Must channels open before inactivating? AB - Experiments on sodium channel inactivation kinetics were performed on voltage clamped crayfish giant axons. The primary goal was to investigate whether channels must open before inactivating. Voltage-clamp artifacts were minimized by the use of low-sodium solutions and full series resistance compensation, and the spatial uniformity of the currents was checked with a closely spaced pair of electrodes used to measure local current densities. For membrane potentials between -40 and +40 mV, sodium currents decay to zero with a single exponential time-course. The time constant for decay is a steep function of membrane potential. The time-course of inactivation measured with the double-pulse method is very similar to the decay of current at the same potential. Steady-state inactivation curves measured with different test pulses are identical. The time course of double pulse inactivation shows a lag that roughly correlates with the opening of sodium channels, but detailed comparisons with the time course of the prepulse current suggest that it is not strictly necessary for channels to open before inactivating. Measurements of the potential dependence of the integral of sodium conductance area also inconsistent with the simplest cases of models in which channels must open before inactivating. PMID- 6268221 TI - The coupling ATPase complex: an evolutionary view. AB - Phospholipid micelles and vesicles, present in the primordial soup, formed both primitive (surface) catalyst and primitive replicative life forms. With the adoption of a common energy source, ATP, integrated biochemical systems within these vesicles became possible - cells. Fermentation within these primitive cells was favoured by the evolution, first of ion channels allowing protons to leak out, and then of an active ATP-driven pump. In the prokaryotic/mitochondria/chloroplast line, the proton channel was such as to be blocked by dicyclohexylcarbodiimide and the adenosine 5' triphosphate phosphohydrolase (ATPase) by 4-chloro 7-nitrobenzofurazan (Nbf-C1). The ATPase was initially simple (4 subunits) but later, possibly concomitant with its evolution to an ATP synthetase, became more complex (8 subunits). One of the steps in evolution probably involved gene duplication and divergence of 2 subunits (alpha and beta) from the largest of the ATPase subunits. From this stage, the general form of the ATPase was fixed, although sensitivity to, for example, oligomycin involved later, after divergence of the mitochondrial and chloroplast lines. A regulatory protein, the ATPase inhibitor, is found associated with a wide spectrum of coupling ATPases. PMID- 6268220 TI - A new method for membrane reconstitution: fusion of protein-containing vesicles with planar bilayer membranes below lipid phase transition temperature. AB - A new method of membrane reconstitution was developed by fusion of channel protein containing vesicles with planar bilayer membranes. The fusion process only occurred below and near the phase transition temperature of the lipid used. We obtained the following results: 1. Our system is solvent-free and vesicles do not come into contact with the air/water interface. This obviates a possible denaturation of hydrophobic proteins. 2. Channel forming proteins and protein complexes, respectively, are active in a frozen lipid matrix. 3. We detected an unknown channel in cilia fragments. 4. Purified acetylcholine receptors form fluctuating channels in a membrane consisting of a pure synthetic lecithin (two component system). PMID- 6268222 TI - [Prolonged changes in hormonal homeostasis after brief circulatory arrest in the small intestine]. AB - It has been established that temporary cessation of blood circulation in the rat small intestine induces alterations in the levels of thyroid and glucocorticoid hormones. These alterations are of the wavy character and can be traced up to 2 weeks after the operation that correlates with duration of previously found functional biochemical, and morphological changes. PMID- 6268223 TI - [Effect of lithium preparations on the toxic effects of adrenaline]. AB - Experiments on rats have shown that intravenous injection of adrenaline in a dose of 0.3-0.4 mg/kg causes cardiac arrhythmia. In this case the primary arrhythmia developing immediately after adrenaline injection is followed by the recovery of sinusal rhythm which was replaced by the secondary arrhythmia. Apart from arrhythmias, there developed pulmonary edema. The animals died 2--3 minutes after adrenaline injections. Lithium chloride and lithium hydroxybutyrate removed the secondary arrhythmia and pulmonary edema. Lithium hydroxybutyrate has proved to be more effective. PMID- 6268224 TI - [Effect of armin on synaptic transmission in frog neuromuscular preparations]. AB - The action of armin, an organophosphorus inhibitor of cholinesterases, on synaptic transmission parameters was studied by means of intracellular registration of end plate potentials and currents (EPP and EPC) in the frog. On 10-minute exposure the increase in the temporary parameters became manifest provided the drug was administered at a concentration of 10(-6) g/ml and over. EPC reversal potential and cholinoreceptor sensitivity to armin did not change substantially. At a concentration of 10-(-8) g/ml armin exerted a potentiating effect on the frequency of miniature EPP and quantum composition of EPP, while that effect was not related to armin anticholinesterase activity. The presynaptic acetylcholine release was suppressed by high concentration of armin (10(-5) g/ml). Under the conditions cited there was a decrease in the depot of the available transmitter quanta in nerve terminals. PMID- 6268225 TI - [Ability of vaccinia viruses to induce expression of p30 retroviruses in continuous mouse cell lines]. PMID- 6268226 TI - [Effect of acetylcholine on the Na, K-ATPase activity of homogenates of rat spleen and lymphosarcoma]. PMID- 6268227 TI - [Metabolism of erythrocyte chalone in vitro]. AB - It has been shown that erythrocytic chalone was bound to the surface of mouse myelokaryocytes after one minute, penetrated them after 30 minutes, disintegrated and excreted in the form of low-molecular mass compounds after 4 hours of incubation. The cells treated with erythrocytic chalone or trypsin are not capable to respond to the repeated action of chalone over 2 hours, which seems likely to be related to the lack of receptor resynthesis during the period under consideration. PMID- 6268228 TI - [Ultracytochemical study of oxidoreductases in the parietal cells of the gastric mucosa in gastric cancer]. AB - Ultracytochemistry was used to study and compare cytochromooxidase, succinate dehydrogenase and NADH-dehydrogenase activity in gastric mucosa parietal cells in health and in gastric carcinoma associated with decreased acidity of gastric juice. The study demonstrated the reduced activity of the enzymes listed in the mucosal parietal cells in gastric carcinoma. This finding is interpreted as a consequence of disturbed energy supply of hydrochloric acid secretion in gastric carcinoma. PMID- 6268229 TI - [Morphofunctional changes in the thyroid glands of rats following lithium chloride administration]. AB - The effect of lithium chloride on the morphological characteristics and function of the thyroid gland of male white rats was studied by histological, histochemical, radioimmunological and radiometric methods. Significant changes in the thyroid parenchyma proper and in the population of parafollicular or C cells were recorded in response to the increased dosage of the substance injected. The lowering of J-accumulative and hormone-binding functions indicates the inhibitory action of lithium chloride both on the phase of hormonogenesis in thyrocytes and on the phase of secretion of thyroid hormones into the blood. Reduction of TTH level in the animals blood plasma suggests that lithium chloride produces the adenohypophysis-mediated action on the thyroid gland. PMID- 6268230 TI - Acquired von Willebrand's disease in association with Wilm's tumor: regression following treatment. AB - A 9-yr-old female presented with a Wilm's tumor and a coagulopathy consistent with von Willebrand's disease. Factor VIII procoagulant activity (VIII C), factor VIII related antigen (VIIIR:Ag), and von Willebrand factor activity (VIII:vWf) were decreased. There was no evidence for a circulating inhibitor of the factor VIII molecular complex. von Willebrand's antigen II (vW AgII), which is deficient in hereditary von Willebrand's disease, was decreased below detectable levels in this patient. The coagulation studies, VIIIR:Ag, and vW AgII levels returned to normal following therapy of the Wilm's tumor. Wilm's tumor must be included as one of the malignancies associated with acquired von Willebrand's disease. Immunofluorescent studies of the tumor specimen showed normal endothelial staining of VIIIR:Ag by semiquantitative techniques and a lack of specific tumor adsorption of VIIIR:Ag The presence of normal amounts of tissue VIIIR:Ag has not previously been demonstrated in acquired von Willebrand's disease. Since we failed to demonstrate an inhibitor in the plasma in this patient, the etiology of the acquired von Willebrand's disease in this patient appears to differ from other cases of acquired von Willebrand's disease. The finding that vW AgII is decreased in this patient, similar to that reported in hereditary von Willebrand's disease, supports the close association of vW AgII to VIIIR:Ag, even though they are immunologically and biochemically distinct. PMID- 6268232 TI - [Histochemical localization of Na+, K+-ATPase in rat submandibular gland. The effects of mineralocorticoid and sodium ion (author's transl)]. PMID- 6268231 TI - Chemotactic deactivation of human neutrophils: protective influence of phenylbutazone. AB - The antiinflammatory drug, phenylbutazone (PBZ), has been studied in terms of its influence on chemotactic deactivation of human neutrophils. When PBZ was present during the time of preincubation of cells with N-formyl-methionyl-phenylalanine (F-Met-Phe), loss of subsequent spontaneous mobility and chemotactic responsivity to F-Met-Phe did not occur. The action of PBZ to protect neutrophils from peptide mediated chemotactic deactivation was found to involve in part its inhibitory influence on hexose monophosphate shunt activity and in part its antagonistic effect on interaction of peptide receptors with N-formyl peptide. Phenylbutazone interfered with binding of N-formyl-methionyl-leucyl-[3H]phenylalanine but not [125I]C5a to the neutrophil, displaced labeled tripeptide bound in the absence of PBZ, increased the dissociation constant (KD) for labeled tripeptide, and limited down regulation of peptide receptor function. These results provide an example of drug-mediated modulation of the interaction of neutrophils with N-formyl peptide and strongly support the possibility that PBZ interacts directly and specifically with the human neutrophil peptide receptor as a competitive antagonist. They also provide an additional example of a compound outside of th N-formyl peptide series that interacts with the peptide receptor. PMID- 6268233 TI - Variation in the THC content in illicitly imported Cannabis products. AB - The tetrahydrocannabinol (THC) content of 304 seizures of illicit Cannabis products was determined using gas chromatography. This procedure results in the conversion of THC acid to THC itself and thus gives the total THC content of the material, which reflects its potency as experienced by the smokers. The study was carried out over three years, thus enabling comparisons to be made between THC levels from a given country of origin over this time span in addition to any variations between the countries. In the early part of the study, herbal cannabis from South East Asia was consistently the best quality and that from the Caribbean the poorest quality. In the third year of the study, the material from South East Asia was in general no richer in THC than material from other areas of the world. Cannabis resins normally had higher THC contents than most herbal material, but the highest levels were found in "hash oil" from the Middle East and the Indian subcontinent. PMID- 6268234 TI - Effect of gender on development and diurnal rhythm of prostaglandin receptors in rat aorta. AB - 1 The prostaglandin endoperoxide H2 analogue, U-46619 (15-hydroxy-11, 9 epoxymethanoprosta-5Z, 13E-enoic acid), was used to determine the effect of gender on the isotonic contractile response of the superfused rat aorta preparation over a 24 h period and at 10 and 16 weeks of age. 2 The maximal responses of the male aortae were 20 +/- 3% and 36 +/- 4% (P less than 0.001) greater than the female at 10 and 16 weeks, respectively. Similarly, sensitivity of the male aorta to the PGH2 analogue increased with age. 3 The male but not the female exhibited a diurnal rhythm in which both the maximum contractile response and sensitivity were significantly decreased at night. 4 We conclude that these gender differences may be related to the secretion of androgen, since reported peak serum testosterone over a 44 h period and testosterone changes with maturation are coincident with the maximum response of male aortae to the PGH2 analogue. PMID- 6268235 TI - Characterization of the kappa-subtype of the opiate receptor in the guinea-pig brain. AB - 1. In homogenates of guinea-pig brain, the characteristics of the binding of [3H] ethylketazocine, an agonist for the putative kappa-receptor, were determined by estimation of the affinity and capacity of binding, by competitive inhibition for the binding site by unlabelled ligands and by selective protection of the binding site from alkylation by phenoxybenzamine. 2. At 25 degrees C the maximum number of binding sites for [3H]-ethylketazocine was about 14 pmol/g fresh brain, of which about 50% were high affinity sites. 3. In competition experiments, the high affinity binding of [3H]-ethylketazocine to the kappa-binding site was readily displaced by several kappa-agonists but not by the selective mu-ligand, D-Ala2, MePhe4, Gly-ol5-enkephalin or the selective delta ligand, D-Ala2, D-Leu5 enkephalin. In contrast, the kappa-agonists tested so far exhibit a high degree of cross-reactivity with the mu-binding site but somewhat less with the sigma binding site. Similar specificities were observed in protection experiments. 4. The approximate proportions of the three subtypes of opiate receptor in the guinea-pig brain are 25% mu-binding sites, 45% delta-binding sites and 30% kappa binding sites. 5. The endogenous opioids, Met-enkephalin, Leu-enkephalin and porcine beta-endorphin have only a low affinity for the kappa-binding site. PMID- 6268236 TI - Pharmacological characterization of the excitatory innervation to the guinea-pig urinary bladder in vitro: evidence for both cholinergic and non-adrenergic-non cholinergic neurotransmission. AB - 1 Field stimulation of strips of guinea-pig isolated urinary bladder with 5 s trains at 0.1 to 15 Hz resulted in frequency-dependent, reproducible contractions. 2 At concentrations of 1 and 4 x 10(-7) M and 1 x 10(-6) M, atropine produced a variable, partial inhibition of contractions at all frequencies but was most effective at frequencies of 3 Hz or more. 3 Tetrodotoxin (TTX), 5 x 10(-7) M, inhibited contractions at all frequencies by 80 to 90%. 4 Physostigmine, 2 x 10(-6) M, significantly enhanced the contractile response to frequencies of less than 10 Hz but did not enhance responses resistant to inhibition by atropine. Hexamethonium, 1 x 10(-4) M, slightly enhanced the contractile response to frequencies of 4 Hz or greater. 5 (+/-)-Propranolol (5 x 10(-6)M), guanethidine (1 x 10(-6)M), phentolamine (5 x 10(-6)M) and clonidine (3 x 10(-8)M) each enhanced the contractile response to field stimulation. 6 Contractile responses obtained in the presence of atropine (4 x 10(-7) M) and guanethidine (1 x 10(-6) M) increased with time and were inhibited 60 to 80% by TTX (5 x 10(-7)M. 7 It is concluded that the cholinergic nervous system contributes, in part, to electrically-induced excitatory contractions of the isolated urinary bladder of the guinea-pig. Concomitant sympathetic stimulation appears to serve an inhibitory role. In addition, a major portion of the contractile response appears to be due to a non-cholinergic non-adrenergic, as yet unidentified, substance. PMID- 6268237 TI - Additive and non-additive effects of mixtures of short-acting intravenous anaesthetic agents and their significance for theories of anaesthesia. AB - 1 The potency of a series of short-acting anaesthetics was established by measuring the duration of the loss of righting reflex following a single bolus injection into the tail vein of male Wistar rats. The agents were, in order of potency, etomidate, alphaxalone, methohexitone, alphadalone acetate and propanidid.2 The potency of binary mixtures of these agents was also assessed to see whether the anaesthetic effects of different agents were additive as classical theories of anaesthesia suggest. Mixtures of alphaxalone and alphadalone acetate, alphaxalone and propanidid and methohexitone and propanidid all showed simple additive effects. Mixtures of alphaxalone and etomidate and of alphaxalone and methohexitone showed a greater potency than would be expected if their effects were simply additive. Mixtures of etomidate and methohexitone were not examined.3 Mixtures of alphaxalone and either methohexitone or pentobarbitone produced a greater depression of synaptic transmission in in vitro preparations of guinea-pig olfactory cortex than would have been expected from the sum of the activities of the individual anaesthetics. Other combinations of anaesthetics did not show similar effects although the interaction between alphaxalone and etomidate was not examined.4 Neither alphaxalone nor pentobarbitone affected the membrane: buffer partition coefficient of the other for a model membrane system.5 These results are interpreted as evidence against the classical unitary hypotheses of anaesthetic action based on correlations of anaesthetic potency with lipid solubility and as supporting the view that different anaesthetics act on different structures in the neuronal membranes to produce anaesthesia. PMID- 6268238 TI - A pilot study of the mechanism of action of desipramine. AB - To test the hypothesis the desipramine alters alpha adrenoceptor function in depressed patients, the effects of clonidine upon growth hormone sedation and blood pressure have been measured in depressed patients before and after treatment with desipramine. After three weeks of treatment the hypotensive and sedative effects of clonidine were inhibited in all patients even though plasma desipramine concentrations at this time varied from 42 to 560 micrograms/l. Growth hormone responses to clonidine were enhanced in five of the six patients but this effect was not statistically significant. These findings are consistent with the hypothesis that in these patients desipramine altered alpha adrenoceptor function: other explanation are discussed. PMID- 6268239 TI - Blood platelets and psychiatry. PMID- 6268240 TI - Extracorporeal glucose monitor. PMID- 6268241 TI - How does acupuncture work? PMID- 6268242 TI - Toxic effect of sampling swabs and transportation test tubes on the formation of intracytoplasmic inclusions of Chlamydia trachomatis in McCoy cell cultures. AB - The ability of Chlamydia trachomatis, immunotype E, to produce intracytoplasmic inclusions in cycloheximide-treated McCoy cells after being exposed to different types of sampling swabs in experimentally infected transport medium was studied. A larger number of inclusions was obtained with cotton-tipped aluminium and rayon tipped plastic swabs than with calcium-alginate-tipped aluminium and cotton tipped wooden swabs (P less than 0.0001). Transport medium stored in glass tubes caused a cytopathic effect when inoculated on to McCoy cell cultures; no such effect occurred with plastic tubes. When cotton-tipped aluminium instead of calcium-alginate-tipped aluminium swabs were used to collect 50 make urethral specimens significantly more were chlamydia-positive (P less than 0.025). This was also true when cotton-tipped aluminium swabs were used instead of alginate tipped swabs in a study of 123 cervical specimens (P less than 0.01). When the calcium-alginate-tipped aluminium and cotton-tipped wooden swabs were shaken in the transport medium after sampling from the male urethra and the cervix, instead of being left in the medium during transport to the laboratory, more specimens were chlamydia-positive and a greater number of chlamydial inclusions were found per culture-positive sample; these results were, however, not statistically significant (P greater than 0.05). PMID- 6268243 TI - Local tissue oxygen tension-cytochrome a,a3 redox relationships in rat cerebral cortex in vivo. AB - Simultaneous measurements were made from rat cerebral cortex, in situ, of focal changes in both tissue oxygen tension (ptO2) and the reduction/oxidation ratio of cytochrome c oxidase (cytochrome a,a3) in order to study relationships between oxygen supply and consumption in small regions of tissue. Local ptO2 was measured with polarographic microelectrodes and the redox state of cytochrome a,a3 with a dual wavelength reflectance spectrophotometer. Increased ptO2, produced by respiration of gas mixtures with elevated O2 and/or CO2 content, was accompanied by increased oxidation of cytochrome a,a3. This confirms that cytochrome oxidase is not fully oxidized in focal brain tissue regions in vivo, as it is in mitochondria isolated in vitro. Decreased ptO2 was accompanied by cytochrome a,a3 reduction. The oxidative changes of cytochrome a,a3 with increases in ptO2 were smaller than the reductive changes associated with decreases in ptO2. Curves relating cytochrome a,a3 redox state to ptO2 were qualitatively alike, regardless of the initial ptO2 value from which they were generated. Thus, the reduction level of cytochrome a,a3 varied with ptO2 on a continuum. This consistent relationship demonstrates that changes in mitochondrial redox state provide an index of relative changes in tissue oxygenation in intact neocortex. The results suggest also that local rates of cerebral oxidative metabolism may not always be constant with changes in local ptO2. PMID- 6268244 TI - Oxidative metabolic responses with recurrent seizures in rat cerebral cortex: role of systemic factors. AB - Simultaneous focal measurements of cerebral oxygen tension and cytochrome a,a3 redox levels were made in rat cortex in order to obtain a direct and continuous assessment of oxidative metabolic changes during serial seizures. Initial seizures evoked by pentylenetetrazol were accompanied by transient increases in tissue pO2 and cytochrome a,a3 oxidation, confirming that oxygen provision is adequate to meet metabolic demand. After some point, subsequent seizures were accompanied by failure of pO2 to increase and failure of cytochrome a,a3 to oxidize, or by decreases in tissue pO2 and shifts in the redox level of cytochrome a,a3 toward reduction, signalling cortical oxygen insufficiency. Whereas early seizures were accompanied by increments in both cerebral blood volume and arterial blood pressure, one or both of these variables failed to increment during later seizures. This was particularly evident following the onset of spontaneously recurring seizures with short intervals between bursts of ECoG activity. These investigations emphasize the importance of systemic factors in determining the cerebral metabolic response to seizures and support the suggestion that neuronal damage in status epilepticus may be the result of derangements of oxidative metabolism. PMID- 6268245 TI - Properties of [3H](3-Me-His2)TRH binding to apparent TRH receptors in the sheep central nervous system. AB - [3H](3-methyl-His2)thyrotropin releasing hormone ([3H]MeTRH) binds to sites in the sheep central nervous system (CNS) whose properties closely resemble both those of CNS binding sites for [3H]TRH and those of pituitary binding sites for [3H]MeTRH. Detailed studies for binding of [3H]MeTRH in the sheep nucleus accumbens and retina have yielded equilibrium dissociation constants of about 4 nM and densities of binding sites of about 3 and 2 pmol/g wet weight, respectively. The binding affinity of [3H]MeTRH was 8- to 10-fold higher than that of [3H]TRH, resulting in much lower non-specific binding with the new ligand. The association reaction had a rate constant of about 2-3 x 10(7) M-1 min 1, while the biphasic dissociation reaction had rate constants of 8-9 x 10(-2) min-1 for the fast phase and 1-2 x 10(-2) min-1 for the slow phase. The regional distribution of binding in the sheep CNS was similar to that observed previously with [3H]TRH. Highest binding outside the pituitary was in the nucleus accumbens area and retina, with another peak in the amygdala-temporal cortex area. Binding was widely distributed, so that no CNS region appeared totally devoid of binding. Nineteen TRH analogs, ranging in potency over 6 orders of magnitude, showed nearly identical abilities to complete for binding of [3H]MeTRH in the CNS areas and in the sheep anterior pituitary gland in side-by-side experiments. These findings argue strongly for identification of [3H]MeTRH binding sites in the CNS as TRH receptors. PMID- 6268246 TI - Alterations in neurotransmitter receptor binding in the spinal cord after transection. PMID- 6268247 TI - Multiple opiate receptors: phylogenetic differences. AB - Both the levels and types of binding sites for opiates and enkephalins appear to be different between species. The most dramatic differences are seen between rats, which have significant levels of both high and low affinity sites, and goldfish, which have only low affinity sites. Binding to both high and low affinity sites is easily displaced by low concentrations of morphine and D-Ala2-D Leu5-enkephalin, suggesting that both represent relevant receptor sites. PMID- 6268248 TI - Changes in size and shape of synaptic connections after visual training: an ultrastructural approach of synaptic plasticity. PMID- 6268249 TI - Subtypes of beta-adrenergic receptors in rat cerebral microvessels. AB - The 125I-labeled iodohydroxybenzylpindolol (IHYP) binding to beta-receptors on brain micro-vessels is inhibited by isoproterenol, epinephrine and norepinephrine, with Ki values of 2 X 10(-7) M, 2.5 X 10(-6) M and 1.2 X 10(-5) M, respectively. A modified Scatchard analysis of the inhibitory effects of practolol, metroprolol and zinterol on IHYP binding has shown that the proportion of beta 2-receptors in our preparation is about 80% of the total beta-adrenergic receptor population. Our data indicate that the beta-adrenergic receptors located on cerebral microvessels are of both beta 1 and beta 2 types, with a predominance of the beta 2 type. PMID- 6268250 TI - Opiate effects on rabbit vagus nerve: electrophysiology and radioligand binding. AB - Intracellular recordings were made from rabbit nodose ganglion cells in vitro. Morphine (up to 100 micro M), normorphine (up to 10 micro M) and D-Ala2, Leu5 enkephalin (DADLE) (up to 5 micro M) each had no detectable effect on the electrical properties of the cell membrane, except for local anesthetic-like actions at the highest concentrations which were not reversed by naloxone. Extracellular recordings were made from the infranodose vagus nerve in vitro using a sucrose gap method. No effects of morphine, normorphine or DADLE were detected on the resting potential, compound action potential or compound action potential enhanced by barium or tetraethylammonium. Moderate levels of stereospecific binding of tritiated dihydromorphine and DADLE were detected in both the nodose ganglion and vagus nerve. It is surmised that the radioligand binding sites on the nodose ganglion and vagus nerve are not functionally linked to detectable electrophysiological effects. PMID- 6268251 TI - Regional changes in brain norepinephrine content in relation to mouse-killing behavior by rats. AB - Three separate series of experiments were conducted as follows: isolation housing, bilateral olfactory bulbectomy, and delta 9-tetrahydrocannabinol (THC) administration. All three experimental manipulations produced an increase in the incidence of mouse-killing behavior. In order to elucidate the possible neural mechanisms mediating the killing response, norepinephrine (NE) content was measured in 6 discrete areas of the brain (the cortex, striatum, amygdala, midbrain, hypothalamus, and pons plus medulla oblongata). Following isolation housing, no significant difference in NE levels of any of the brain areas was demonstrated between the aggregated and isolated rats, nor between the killer and nonkiller rats. The rats with olfactory bulbectomy exhibited high NE content in the hypothalamus as compared with the intact or sham-operated rats, but there was no significant difference between the killer and nonkiller rats. After injections of THC, NE content in both the hypothalamus and pons plus medulla oblongata was decreased independent of the manifestation of killing response. The evidence indicates no regional change in brain NE levels specific to the killing response and suggests that brain NE may not participate in the mediation of mouse-killing behavior. PMID- 6268252 TI - In vitro and in vivo depolarization coupled efflux of ascorbic acid in rat brain preparations. AB - The depolarization-coupled efflux of endogenous ascorbate is demonstrated using rat synaptosome preparations and a rat cortical cup method. Ascorbate and catecholamines (monitored as a methodological control) were quantitated by high pressure liquid chromatography with electrochemical detection. In vitro potassium ion induces ascorbate efflux in a concentration-dependent, although calcium ion dependent, manner. Veratridine also induces ascorbate efflux and its effect can be blocked by tetrodotoxin. In vivo, ascorbate efflux was likewise stimulated by increased potassium ion and by veratridine. In addition, electrical stimulation of medial lemniscus was accompanied by an increased efflux of ascorbate from somatosensory cortex. These results are intriguing in light of the recent evidence for the interaction of ascorbate with several neurotransmitter systems. PMID- 6268254 TI - Phencyclidine-induced alterations of rat electrophysiology. AB - Phencyclidine (PCP) at high doses causes both excitation and depression in the rat. The visual evoked potential (VEP) was measured in rats following PCP administration in doses ranging from 1 mg/kg to 56 mg/kg. Consistent lengthening of VEP latencies suggests that PCP has an unusual inhibitory effect on visual function in the presence of the excitatory signs of bilaterally synchronous cortical spiking. The epileptogenic properties of PCP are quite evident in rats. PMID- 6268253 TI - Effect of sympathetic input on ontogeny of beta-adrenergic receptors in rat pineal gland. AB - The ontogeny of beta-adrenergic receptors was investigated in the pineal glands of rats 1-64 days of age. The density of beta-receptors increased about 3-fold between 1 and 16 days of age and decreased slightly by 64 days, correlating temporally with the development of the sensitivity of adenylate cyclase to norepinephrine in pineal gland. Preventing adrenergic innervation of the pineal gland by neonatal ganglionectomy or decentralization failed to prevent the development of beta-adrenergic receptors in pineal gland. Bilateral adrenal demedullation alone or in combination with ganglionectomy also failed to prevent the normal developmental increase of beta-receptors in the gland. These results, showing that the ontogeny of pineal beta-receptors correlated temporally with that of the responsiveness of adenylate cyclase to adrenergic neurohormones, support the hypothesis that the responsiveness of tissues ot beta-agonists is dependent on the development of the beta-receptor. In addition, these experiments show that the beta-adrenergic receptor can develop even in the absence of sympathetic innervation or circulating catecholamines produced by the adrenal medullae. PMID- 6268255 TI - Central injection of a sigma opioid receptor agonist alters body temperature of cats. AB - The prototype sigma opioid receptor agonist N-allyl-normetazocine (SKF 10,047) was injected into the third cerebral ventricle of conscious, unrestrained cats, and their temperature was monitored automatically from the retroperitoneal space. In a cold environment (0 degrees C) a small, but not dose-related, hypothermia occurred after doses of 100-500 micrograms. This response was not antagonized by naloxone given intraventricularly either 15 min before or 1 hr after the opioid. A smaller hypothermia resulted after 250 micrograms SKF 10,047 when the environmental temperature was 22 degrees C, whereas hyperthermia developed in a hot environment (34 degrees C). Thus SKF 10,047 appears to allow body temperature to drift, upward in the heat and downward in the cold, a pattern indicative of thermoregulatory depression. These results are similar to those obtained in the first 2-3 hr after pentazocine administration, and they support a previous classification of the initial temperature response to centrally injected pentazocine as due to stimulation of sigma opioid receptors. PMID- 6268256 TI - [Formation of superoxide anion in phagocytosis of bacteria by polymorphonuclear leukocytes (author's transl)]. PMID- 6268257 TI - [In vivo effects of conjugated estrogens on the insulin receptor and on glucose binding in isolated adipocytes of male rats]. AB - Studies have been carried out with labeled substrates on isolated adipocytes of male rats injected with sulpho-conjugated estrogens. Three days treatment did not affect insulin receptor concentration or affinity in the cells. Conversely glucose uptake is reduced in the absence of insulin, or by reduced responsiveness in the presence of it. After ten days treatment, insulin binding impaired on account of reduced receptor concentration, whereas glucose uptake was normal in the absence of insulin, increased at low and decreased at high insulin concentration, on account of both decreased responsiveness and increased sensibility to insulin. Thus it is suggested that estrogens acts on glucose uptake prior to act on the insulin receptor in the adipocytes. PMID- 6268258 TI - [Modification, by lithium, of catalepsy induced by central cholinergic stimulants and morphine-like drugs]. AB - After unique injection LiCl enhances, in albino rat, catalepsy induced by arecoline and oxotremorine perhaps by adenylcyclase inhibition and/or decrease of acetylcholine synthesis. After repetitive injection of LiCl during 5 days, this phenomenon is not observable, probably owing to increase of acetylcholine synthesis. After unique injection of LiCl enhances catalepsy induced by dextromoramide, probably on account of cholinergic properties of this drug. In contrast catalepsy induced by morphine or pethidine is suppressed. This constatation would depend on opposite influence upon cerebral neuromediators : lithium diminishing cerebral serotonin and striatal acetylcholine levels and morphine increasing them. After repetitive injections these phenomenons are not observable. PMID- 6268260 TI - Uptake of collagenolytic enzymes by bone cells during isolation from embryonic rat calvaria. PMID- 6268259 TI - Lattice parameters and cation distribution of solid solutions of calcium and lead hydroxyapatite. AB - Solid solutions of calcium hydroxyapatite (CaOHA) and lead hydroxyapatite (PbOHA) of the formula Ca10-x Pbx (PO4)6 (OH)2 were prepared by coprecipitation followed by heating at 800 degrees C in a steam of CO2-free water vapor of 1 atm. The samples were apatitic in the range 0 less than x less than 6 and contained lead phosphates as a second phase at higher Pb/Ca ratios. Lattice parameters and cation distribution of the apatitic samples were determined by X-ray diffraction. The lattice parameters varied linearly with x in the range considered, whereas all Pb2+ were located in the six-fold position for cations. There was a miscibility gap in the apatite series of solid solutions in the range 1 less than x less than 4, whereas apatites in the range 6 less than x less than 10 were not stable under the conditions of preparation. It is concluded that apatites in the range 4 less than x less than 6 represent a minimum in the free energy of solid solutions between CaOHA and PbOHA. PMID- 6268262 TI - Cytochrome c reduction by cysteine plus copper: a pseudosubstrate system for cytochrome c oxidase. AB - Cysteine alone reduces horse heart cytochrome c very slowly (k approximately or equal too 1.0 M-1s-1) with a rate constant virtually identical in high and low ionic strength buffers. Copper catalyzes this reaction increasing the rate by a factor of 10(5) in 50 mM phosphate and by a factor of 10(6) in 10mM Tris buffers. When ferricytochrome c and cysteine are mixed in an oxygen electrode a "burst" of oxygen uptake is seen, the decline in which parallels the reduction of cytochrome c. When cytochrome oxidase is added to such a mixture two routes of electron transfer to oxygen exist: enzymatic and ferricytochrome c dependent nonenzymatic. Both processes are sensitive to cyanide, but azide inhibits only the authentic cytochrome c oxidase catalyzed process and BCS the ferricytochrome c stimulated reaction. PMID- 6268261 TI - Growth failure in vitamin D-deficient rat pups. AB - Vitamin D-deficient rat pups were produced by feeding normal impregnated rats a diet deficient in vitamin D after mating. The rat pups appeared normal at birth but stopped growing at 1 week of age. Despite this growth failure, these pups were normocalcemic. Analyses of calvaria from a similar group of dams given vitamin D3 showed that these dams mobilized skeletal calcium to meet the calcium requirements of their growing pups. PMID- 6268263 TI - Subclinical infectious bursal disease in commercial broiler flocks in Saskatchewan. AB - Five commercial broiler flocks, not vaccinated for infectious bursal disease virus, derived from infectious bursal disease virus-vaccinated breeder flocks were surveyed for evidence of bursal damage and infectious bursal disease virus infection. They were compared with two groups of birds raised in isolation. Serum samples from one day old chicks contained maternal anti-infectious bursal disease virus antibodies which declined to undetectable levels by four weeks of age. Serum antibody levels remained undetectable in both control groups and one commercial flock, whereas four of the five commercial flocks had actively produced anti-infectious bursal disease virus antibodies by slaughter age. The weight of bursae from infectious bursal disease virus-positive flocks declined as compared to controls after four weeks of age. The decline in weight correlated with the appearance of histopathological lesions. Infectious bursal disease virus antigen was demonstrated in selected infected bursae and infectious bursal disease bursae and infectious bursal disease virus was isolated from some of these damaged bursae. Clinical infectious bursal disease was not observed in any of the commercial flocks. The importance of subclinical bursal damage and immunosuppression is discussed. PMID- 6268264 TI - Comparative virulence of different bovine rotavirus isolates. AB - Intestinal loops, ligated in colostrum-deprived calves were used to compare the virulence of four isolates of bovine rotavirus. Histopathological studies were carried out on infected and control loops and measurements of villous length, crypt depth, villus:crypt ratio and crypt mitotic index were recorded. Pathological changes associated with the rotaviruses included villous atrophy, flattening of absorptive epithelium and reduced villus:crypt ratios. The changes were confined to infected intestinal loops in which the presence of virus was demonstrated by specific immunofluorescence. Consistent differences in the measured histopathological changes suggested differences in virulence among the rotavirus isolates tested. The least virulent rotavirus isolate had a polypeptide electrophoretic pattern that differed from the other three more virulent isolates. PMID- 6268265 TI - An enzyme-linked immunosorbent assay (ELISA) for infectious bursal disease virus. AB - The application of the indirect enzyme-linked immunosorbent assay (ELISA) for detection of infectious bursal disease virus antibodies in chicken serum was investigated. The test procedure involved the coating of concentrated infectious bursal disease virus antigen onto polystyrene tubes, followed by the addition of chicken anti-infectious bursal disease virus serum and horseradish peroxidase labeled rabbit anti-chicken globulin. As an indicator substrate, 5-aminosalicylic acid, with the oxidant H2O2 was added. The reaction was stopped by 3M NaOH and the colour intensity of the reaction mixtures read in a spectrophotometer at 449 nm. The ELISA test was found to be a precise, sensitive and reproducible means of measuring infectious bursal disease virus antibodies in chicken and turkey sera. PMID- 6268266 TI - Induced latency in pseudorabies vaccinated pigs. AB - A latent pseudorabies virus infection was established in pigs despite vaccination with a modified-live pseudorabies virus vaccine. Although the vaccinated pigs developed high concentrations of antibody, virus was recovered from the tonsils and lungs of pigs treated with dexamethasone three months after inoculation with virulent virus. These results may explain why vaccination programs have failed to eliminate the persistence and spread of virulent pseudorabies virus in infected herds. PMID- 6268267 TI - Primary adenoid cystic carcinoma of the esophagus. AB - Primary adenoid cystic carcinoma or cylindroma of the esophagus is rare, only 22 cases having been reported previously. The histogenesis of this tumour is disputed, but it is believed to arise from the submucosal glands. A 75-year-old man with a cylindroma of the esophagus underwent radical excision of the tumour and has been clinically disease-free and asymptomatic since his operation in February 1979. Despite the poor results of surgery in the small number of patients reported in the literature, this unusual type of adenocarcinoma of the esophagus should be treated like epidermoid carcinoma--by radical excision. PMID- 6268268 TI - Survival following breast cancer surgery in the elderly. AB - A retrospective analysis was performed on a series of 780 patients with breast cancer who underwent surgery, with emphasis on survival in the 138 patients over 70 years of age (elderly group). Absolute survival rates were determined using life table methods. Relative survival figures were derived from absolute figures by adjusting for expected longevity in each group. Patients over 70 years of age had overall 5 and 10 year absolute survival rates of 54% and 41%, respectively, which did not differ significantly from survival rates of younger patients. Relative five-year survival rates for the elderly were actually higher than those of younger patients, being 90% for those with local disease and 65% for those with regional disease. Survival in the elderly was comparable to that of younger patients, irrespective of race, type of surgery, histology or tumor size. These findings support the conclusion that there is little justification for avoiding conventional operative treatment in elderly patients with breast cancer solely on the basis of advanced age. PMID- 6268269 TI - Thoracic and elective brain irradiation with concomitant or delayed multiagent chemotherapy in the treatment of localized small cell carcinoma of the lung: a randomized prospective study by the Southeastern Cancer Study Group. AB - A prospective randomized study was carried out to compare the effectiveness of concomitant or delayed multiagent chemotherapy combined with irradiation to the primary tumor and regional lymph nodes and to the brain in a group of 70 patients with histologically proven small cell undifferentiated carcinoma of the lung. Complete and partial response in both groups was comparable, and the overall survival was comparable. However, relapse-free survival was significantly higher in patients receiving concomitant chemotherapy and irradiation in comparison with the radiotherapy alone group. Disease-free survival was higher in the concomitant chemotherapy-radiotherapy patients, although survival was not significantly modified, probably because of suboptimal chemotherapy. The initial intrathoracic failure rate was 40.7% inthe concomitant chemotherapy-irradiation group, compared with 53.8% in the radiotherapy-alone patients. None of the patients receiving delayed chemotherapy following the radiotherapy recurrence showed significant tumor response to the drugs. The incidence of distant metastasis was slightly lower in the chemotherapy groups. Brain metastases were noted in 7% of the patients in both groups. Increased intrathoracic recurrences were noted in patients with lower doses of irradiation. Nine of 13 patients treated with inadequate portals developed intrathoracic recurrences in comparison to 13 of 40 treated with adequate irradiation fields. The study emphasizes the need for intensive chemotherapy and adequate radiation therapy to improve survival of patients with small cell undifferentiated carcinoma of the lung. Additional trials are necessary to assess the role of each modality in the management of these patients. PMID- 6268270 TI - A study of immunoreactive calcitonin (CT), adrenocorticotropic hormone (ACTH) and carcinoembryonic antigen (CEA) in lung cancer and other malignancies. AB - Levels of immunoreactive ACTH and calcitonin (CT), as well as CEA, were determined serially in 144 patients with lung cancer and in 62 patients with metastatic carcinoma to the lungs. Patients with neoplasms not involving the lungs, with nonmalignant blood dyscrasias, and with chronic obstructive pulmonary disease were studied, as were normal control subjects. In 55-91% of lung cancer patients, elevated values of CT were detected; the frequency of elevation varied with cell type and stage. The highest values (mean 1346 +/- 2534 pg/ml) were found in patients with extensive small cell lung carcinoma (SCLC) and were significantly greater than the values for patients with SCLC confined to one hemithorax (196 +/- 287.7 pg/ml, P less than 0.005). ACTH levels were elevated less frequently (24-46%) and were highest (192 +/- 200.9 pg/ml) in patients with extensive small cell carcinoma, although Cushing's syndrome was observed only once. Agreement between all three tumor markers was seen in 25-50% of lung cancer patients; the percentage depended on cell type. Calcitonin levels paralleled changes in the clinical status and tumor burden in 89% of SCLC patients, while ACTH levels reflected the clinical course in 67%. In six patients with small cell carcinoma in remission, rising levels of CT, ACTH, and CEA preceded clinical evidence of relapse, in oe patient, by as long as five months. Among 129 patients with conditions other than primary lung cancer, CT levels were highest (232 +/- 328 pg/ml) in those with cancer metastatic to the lungs and/or pleura; there was no; association between CT levels and the presence of bone metastases. PMID- 6268271 TI - Wilms' tumor of the uterus: the first report of the literature. AB - The first case of primary Wilms' tumor of the uterus is described. It occurred in a 14-year-old girl. Microscopically, embryonal tubules, glomeruli, and blastema were identified within a myxomatous stroma. No teratomatous elements were found. The tumor arose in the uterus, permeated the endocervical canal, filled the vagina, and infiltrated the Douglas cul-de-sac and the left broad ligament through the posterior vaginal fornix. Comments are made on the histogenesis and histologic pattern of the tumor. PMID- 6268272 TI - Undifferentiated small cell carcinoma of the pancreas: a report of five cases. AB - Of 485 pancreatic malignancies diagnosed at Hines Veterans Administration Hospital from 1951 to 1979, five cases were undifferentiated carcinoma proved on postmortem examination. The tumors are histologically akin to the more frequently encountered oat cell carcinoma of the lung. Their clinical manifestation and rapid, fatal course closely resemble that of the ductal adenocarcinoma of the pancreas. A possible nonislet cell derivation of the neoplasm is postulated. PMID- 6268273 TI - Menopausal estrogen use and risk of breast cancer. AB - To assess the relationship of menopausal estrogens to breast cancer risk, the authors conducted a case-control study among 881 cases and 863 controls identified through the Breast Cancer Detection Demonstration Project (BCDDP). Use of estrogens was associated with a relative risk (RR) of 1.24 (95% C.I. 1.0-1.5), with higher risks observed among users of high-dose preparations. Hormone effects predominated among women who received them following bilateral oophorectomy (RR = 1.54), obliterating the protective effect normally associated with the operation. In this group, risk increased with years of estrogen use, reaching risks of 2-3 for users of ten or more years. High risks were also observed among oophorectomized women who used hormones in the presence of other risk factors, including nulliparity, family history of breast cancer, and benign breast disease. These results suggest a possible, although complex, relationship between estrogen use and risk of breast cancer. PMID- 6268274 TI - Cells of origin of pancreatic cancer: experimental animal tumors related to human pancreas. AB - Human pancreatic adenocarcinoma is traditionally believed to be ductal in origin, primarily due to the presence of complexes of tubules interpreted as being derived from ductular proliferation. Although observations in various animal models of pancreatic tumors suggested that acinar cells wee undergoing dedifferentiation to form tubular complexes, this process was difficult to reconcile with an acinar arrangement of the pancreas. Using three-dimensional reconstructions and retrograde injections, it was concluded that the normal pancreas actually has a tubular arrangement. The tubules branch, curve, and anastomose. By losing zymogen granules and decreasing in height, acinar units become recognized as ductule-like structures. Therefore, the presence of tubular complexes should not be taken to indicate that carcinogenesis has taken place or to eliminate acinar cells as possible cells of origin of adenocarcinoma, which by present criteria would be classified as ductal. PMID- 6268275 TI - Bilateral cystic nephroblastomas and botryoid sarcoma involving vagina and urinary bladder in a child with microcephaly, arhinencephaly, and bilateral cataracts. AB - The case of a 1-year-old infant with bilateral cystic nephroblastomas, a botryoid sarcoma involving the vagina and urinary bladder, microcephaly, arhinencephaly and bilateral cataracts is reported. The unusual association of these lesions suggests a syndrome due to genetic abnormalities. PMID- 6268276 TI - Ectopic adrenocorticotrophic (ACTH) syndrome and small cell carcinoma of the lung assessment of clinical implications in patients on combination chemotherapy. AB - Small cell carcinoma of the lung is the tumor most commonly associated with ectopic ACTH production and hypercortisolism. The relationship between this paraneoplastic endocrine syndrome and the clinical course of the tumor is examined in this review of patients with the ectopic ACTH syndrome and small cell carcinoma seen at The Johns Hopkins Oncology Center between 1973 and 1979. Five of 157 (3.2%) patients with small cell carcinoma were clinically diagnosed as having the ectopic ACTH syndrome. The onset of this endocrine syndrome appeared to coincide with a more aggressive phase of the course of small cell carcinoma. Further analysis of these cases suggests that the development of the ectopic ACTH syndrome may reflect changes in cell populations within the tumor and/or alterations in tumor behavior with time and perhaps with the effects of drug therapy. PMID- 6268277 TI - Adriamycin and methyl-CCNU combination therapy in hepatocellular carcinoma: clinical and pharmacokinetic aspects. AB - Twenty-one patients with unresectable hepatocellular carcinoma (hepatoma) were treated with adriamycin (15-45 mg/m2 q21 D) and methyl-CCNU (75-150 mg/m2 q 63 D) with dosage adjusted for hepatic dysfunction. Objective response frequency was 14% with all responses occurring in patients with normal pretreatment bilirubin levels. Median survival of all patients was 87 days. Initial bilirubin levels greater than 2 mg/dl predicted for decreased survival (median 30 days vs. 115 days, P less than 0.05). Only moderate hematologic toxicity was observed. Plasma profiles of Adriamycin and adriamycinol were determined during 11 courses of Adriamycin administration in seven of these patients. Despite moderately elevated transaminase levels (all cases) and bilirubin levels (three cases), plasma Adriamycin profiles in hepatoma patients were not elevated (terminal half-life of 30 hours) and were indistinguishable from that of non-hepatoma patients with normal liver functions. However, delayed appearance of peak levels and prolongation of terminal half-lives were routinely observed for adriamycinol, a major metabolite of Adriamycin. This resulted ina significant increase in the CXT (concentration X time) ratio of adriamycinol/Adriamycin in hepatoma patients compared with nonhepatoma patients (2.36 +/- 2.12 vs 0.76 +/- 0.31, (P less than 0.05). We conclude that the combination of relatively mild toxicity and normal Adriamycin disposition indicates unusual tolerance to Adriamycin therapy for patients with hepatoma and cirrhosis. As a result, severe dosage adjustments of Adriamycin may not be indicated for all such patients having only moderate hepatic dysfunction. PMID- 6268278 TI - The indications for and limitations of bone scintigraphy in osteogenic sarcoma: a review of 55 patients. AB - The value of radioisotope bone scanning at the time of presentation and serially during follow-up has been evaluated in 55 patients with biopsy-proven osteogenic sarcoma. Many of the patients studied were treated with adjuvant chemotherapy. Bone metastases were detected at presentation in only one patient and in a second patient, proximal extension of the primary tumor not evident on radiographs was demonstrated by the radioisotope technique. During fellow-up, 20 patients experienced bone metastases and each had an abnormal bone scan. Eleven of these patients were asymptomatic for bone metastases at the time the scan became abnormal. Seven patients experienced bone metastases as their first site of tumor recurrence. The detection rate for soft tissue metastases was low, but the scan indicated stump recurrence in three patients. Although the yield is small, bone scanning is justified at presentation be cause the results may profoundly after the management. During follow-up, routine bone cans are indicated in all patients, whether they have symptoms or not. PMID- 6268279 TI - Preliminary studies of the uridine kinase activity of human colorectal adenocarcinomas. AB - Relatively low uridine-cytidine kinase activities in 22 surgical specimens of human colorectal adenocarcinomas have been demonstrated, in comparison with those of other neoplasms studied. The kinase activities averaged 1.1 nmoles/min/mg of protein; however, four of the specimens exhibited significantly higher levels of enzyme activity than the average, a deviation that could not be correlated with any properties of the tumors. Of the 22 neoplasms, 86% were moderately differentiated; and 14% were poorly differentiated. Staging disclosed 9% Dukes' A neoplasms, 41% Dukes' B, and 50% Dukes' C. The moderately differentiated group included four mucinous tumors; the poorly differentiated only one; none was of the signet-ring cell type. The kinetic characteristics of the uridine kinase activity of one colonic adenocarcinoma were studied in detail; the apparent Michaelis constants for uridine and adenosine 5'-triphosphate were 0.37 x 10(-3) M and 1.07 x 10(-3) M, respectively, and the enzyme required Mg2+ for maximal activity (at 30-42 C). PMID- 6268280 TI - Proliferating trichilemmal cyst: a simulant of squamous cell carcinoma. AB - Comparison of 50 proliferating trichilemmal cysts with 50 "ordinary" trichilemmal cysts indicated that both types almost invariably occurred on the scalps of women, were diagnosed clinically as cysts, followed a benign course, and featured trichilemmal keratinization. A spectrum was observed from trichilemmal cyst with minimal hyperplasia, to full-blown proliferating trichilemmal cyst. Occasionally, patients had ordinary trichilemmal cysts on their scalps associated with a proliferating trichilemmal cyst. In addition to trichilemmal keratinization, which is characteristic of the follicular isthmus, proliferating trichilemmal cysts showed a wider range of differentiation, including features of the follicular infundibulum, the lower nonkeratinizing portion of the follicular outer root sheath, and sebaceous cells. Intense inflammatory infiltrate and cellular atypia, sometimes of significant proportions, were also seen in proliferating trichilemmal cysts. It is concluded that trauma and inflammation may induce a trichilemmal cyst to proliferate and show a broader spectrum of pilosebaceous differentiation and cellular atypia of pseudocarcinomatous proportions, while maintaining its benign biologic behavior. PMID- 6268281 TI - Carcinoembryonic antigen levels as an indicator of the primary site in metastatic disease of unknown origin. AB - In 542 patients with metastatic disease arising from a known primary site, elevated CEA levels (greater than 10 ng/ml) were most often associated with metastatic disease originating from entodermally derived organs, breast, and mucinous ovarian primaries. This observation held true, in general, in a small series of 32 patients with metastatic disease arising from a primary site that had been unknown, but that was identified. Thus, although a CEA level below 10 ng/ml is of no use in pointing to a particular primary site, a value above 10 ng/ml suggests the site is more likely to be in an entodermally derived organ, breast or ovary containing a mucinous carcinoma. If liver metastases are present, there is an increased probability that the primary site will be found in the large bowel or pancreas. PMID- 6268282 TI - Racial survival patterns for lung cancer in Hawaii. AB - From 1960 through 1974, the Hawaii Tumor Registry identified 1895 cases of lung cancer with either small cell or non-small cell carcinoma among the five main racial groups in the islands. There were 650 Caucasians, 549 Japanese, 362 Hawaiian, 173 Filipino and 161 Chinese patients. Analysis revealed that Caucasians with non-small cell carcinoma had a significantly poorer five-year survival rate than Chinese, Filipino, or Japanese patients after simultaneous adjustment for differences in sex, age at diagnosis, stage, and socioeconomic status. Men, older patients, patients with regional or distant disease, and patients in a middle or low socioeconomic status also did worse than the others. When the 170 patients with small cell carcinoma were compared with 1725 patients with non-small cell carcinoma, patients with small cell carcinoma had significantly poorer survival rates after five years. PMID- 6268283 TI - Radiotherapy in the management of locally advanced lung cancer of all cell types: final report of randomized trial. AB - Between 1975 and 1978, 343 evaluable male patients with a diagnosis of locally advanced lung cancer of all cell types were entered in Protocol 15. The patients had unresectable or inoperable tumor limited to one hemithorax and no evidence of distant metastases. The cell-type distribution was as follows: squamous cell carcinoma (Sq CC) 137 (40%); positive cytology 66 (19%); large cell carcinoma 57 (17%); small cell carcinoma (SCC) 46 (13%) and adenocarcinoma 37 (11%). An intermediate course of irradiation (ICI) of 5000 rads in 25 fractions, 200 rads each, in 5 weeks was compared with a short course of irradiation (SCI) of 4200 rads in 15 fractions, 280 rads each, in 3 weeks (equal Nominal Standard Dose). The effectiveness of low dose irradiation to control subclinical brain metastases was studied and was reported separately. The median survival for all 343 patients was 38 weeks. There was no significant difference in survival, response and control rate between the 191 ICI and the 152 SCI patients. The following factors had a significant individual influence on survival: initial performance status, ambulatory vs. nonambulatory, P = 0.006; histology, Sq CC vs. other cell types (OCT), P = 0.0007; prior surgery, less than 6 weeks vs. greater than 6 weeks, p = 0.04; tumor size, diameter less than 6 cm vs. greater than 6 cm, P = 0.05 and weight loss less than 5% vs. greater than 5% in the previous 6 months, P = 0.01. The overall response rate (CR or PR) was 38%. The median duration of response was shorter for the ICI group when compared with the SCI group, 18.4 vs. 34.4 weeks, P = 0.02. The presence of partial or complete response enhanced the median survival 50 vs. 31 weeks. Cell type, Sq CC vs. OCT was an important factor for the duration of response, 49 vs. 21 weeks, P = 0.0006. The complication rate was similar for the 191 ICI patients when compared with the 152 SCI patients. There were however, two patients with radiation myelopathy among the SCI patients and none among the ICI patients. PMID- 6268284 TI - Medullary carcinoma of breast: an immunohistochemical study of its lymphoid stroma. AB - Immunoperoxidase staining for IgA, IgG, IgM, and secretory component (SC) was performed on ten cases each of medullary carcinoma and infiltrating duct carcinoma of breast. Plasma cell-rich stroma of medullary carcinoma was found to contain predominantly IgA plasma cells. Tumor cells also contained IgA and SC. In contrast, the few plasma cells of infiltrating duct carcinoma were found to be predominantly IgG type, and the tumor cells contained none or very small amounts of IgA and SC. Because the presence of IgA plasma cells and IgA and SC in lining epithelial cells are characteristic features of organs of the secretory Ig system, these findings in medullary carcinoma may suggest a good degree of functional differentiation of these tumor cells and correlate well with the well known favorable prognosis associated with this tumor. PMID- 6268285 TI - Gastric cytomegalovirus infection in bone marrow transplant patients: an indication of generalized disease. AB - Cytomegalovirus infection in immunosuppressed patients is well known. It usually appears as an interstitial pneumonitis that may progress to a disseminated viral infection. The authors report on two patients who, after bone marrow transplantation, had signs and symptoms of gastric ulceration as the initial manifestation of cytomegalovirus infection. Both died with disseminated cytomegalovirus infection. Though gastric presentation is unusual for cytomegalovirus infection, epigastric pain and gastrointestinal hemorrhage in a bone marrow transplant patient may herald a potentially lethal viral infection. PMID- 6268286 TI - Cancer of the vulva: a review. AB - Localized carcinoma of the vulva in situ can be treated by wide local excision and continued close observation. Skinning vulvectomy, with or without subsequent skin grafting, is now well accepted as a treatment of Multifocal preinvasive disease. Microinvasive carcinoma of the vulva, on the other hand, is not treated with vulvectomy alone since the regional lymph nodes must be accurately assessed. The currently accepted treatment of invasive carcinoma of the vulva is radical vulvectomy and bilateral groin lymph node dissection. No longer is pelvic lymph node dissection to be considered a routine part of this therapy but is included only under specific circumstances. On rare occasion a more radical procedure such as anterior or posterior pelvic exenteration is considered appropriate therapy when the geographic location of the tumor requires this approach. The treatment of recurrent disease is influenced by its extent and location and must be tailored for the individual patient. Palliative vulvectomy is still used as a treatment of the far advanced disease in an attempt to improve personal and social hygiene, as well as to control serious infection and to prevent localized hemorrhage. The role of x-ray therapy in the treatment of carcinoma of the vulva is discussed. PMID- 6268287 TI - Trophoblastic tumors--prognostic factors. PMID- 6268288 TI - The potential for radiation sensitizers and radiation protectors combined with radiation therapy in gynecologic cancer. AB - Radiation sensitizers are agents which can increase the lethal properties of ionizing radiation when administered in conjunction with radiation therapy. They increase radiosensitivity without being innately toxic and give rise to significant increase in the radiation sensitivity of neoplasm over normal tissues. Much laboratory work, mostly in vitro, has shown that many chemical compounds can act as radiation sensitizers. The practicality depends upon the exploitation of the differences between normal and malignant cells when radiation sensitizers are used. Many tumors contain hypoxic cells which are relatively resistant to the lethal effects of ionizing radiation. In human tumors, these hypoxic cells present a potential barrier to successful treatment. The application of chemical radiosensitizers active against hypoxic cells offers great potential for improvement in cancer management using radiation therapy. Data is presented to illustrate the usefulness of these agents in gynecologic cancer. PMID- 6268289 TI - Chromosomes and cell surface markers of marmoset lymphocytes and Epstein-Barr virus-transformed marmoset cell lines. AB - The G-banded karyotypes of both normal lymphocytes and Epstein-Barr virus (EBV) transformed lymphocytes of cotton-topped marmosets (Saguinus oedipus) were examined. The marmoset lymphocytes and EBV-transformed lymphoblastoid cells had normal diploid chromosomes (2n = 46) with no specific cytogenic change associated with transformation in vitro. EBV-transformed marmoset lymphocytes expressed the cell surface markers of B lymphocytes and EB viral antigens. PMID- 6268290 TI - Variant translocation in Burkitt's lymphoma: 8;22 translocation in a French patient with an Epstein-Barr virus-associated tumor. AB - A variant translocation t(8;22)(q23;q11) has been found in tumor cells from a 19 year-old white man with an Epstein-Barr virus-associated Burkitt's lymphoma (BL). The tumor, which appeared 2 years after the patient had infectious mononucleosis, bore histopathological features characteristic of BL, although only the lymph nodes in the cervical region were involved. This case and some other recent cytogenetic observations of nonendemic BL emphasize the importance of chromosome #8 rearrangement in this B-cell-type lymphoma. PMID- 6268291 TI - Stability of C-banded and C-bandless microchromosomes in clonal sublines of the RVP3 mouse tumor grown serially in vivo. AB - Karylogic studies were performed on three monocellular clones derived from mouse RVP3 cells, which had been originally transformed with the Prague strain of Rous sarcoma virus. All clones that had originally contained a stable number of microchromosomes, continues to retain them after prolonged passage in vivo. Centromeric heterochromatin was absent in 32% of the microchromosomes as revealed by C-banding technique. The stability of microchromosomes either positive or negative for centromeric heterochromatin is discussed in relation to double minute chromatin bodies found in early passages of RVP3 tumor cells. PMID- 6268292 TI - Epidemiologic association between virus-negative feline leukemia and the horizontally transmitted feline leukemia virus. AB - About two-thirds of the natural cases of feline leukemia-lymphoma are assumed to be caused by the feline leukemia virus (FeLV) because they occur in cats, which harbor this agent, and FeLV will induce the disease under laboratory conditions. Epidemiological evidence is presented which associates cases of naturally occurring 'virus negative' feline leukemia with exposure to FeLV. PMID- 6268293 TI - Carcinogenic effect of nitrosopyrrolidine, nitrosopiperidine and nitrosohexamethyleneimine in Fischer rats. AB - Three homologous cyclic nitrosamines, nitrosopyrrolidine, nitrosopiperidine and nitrosohexamethyleneimine, were administered to groups of 20 female F344 rats in drinking water, as 0.9 mM solutions. Treatment with the latter 2 compounds lasted 28 weeks, at which time several animals had died with esophageal tumors. All of the animals in these 2 groups were dead by the 36th week of the experiment. Most of the animals given nitrosohexamethyleneimine also had angiosarcomas of the liver, and a few hepatocellular carcinomas were seen. Treatment with nitrosopyrrolidine lasted 50 weeks and the first animal in the group died at the 63rd week with an hepatocellular carcinoma. By the 110th week, almost all of these animals had died with the same type of tumor, and the 2 survivors were then killed. Many of the hepatocellular carcinomas had metastasized. There were no tumors of the liver in the rats treated with nitrosopiperidine. PMID- 6268294 TI - Prognostic factors in small cell carcinoma of the lung: a cancer and leukemia group B study. AB - Prognostic factors were studied in 224 patients with small cell carcinoma of the lung entered in a Cancer and Leukemia Group B protocol. Extent of disease was the major predictor of complete remission (CR) frequency and survival greater than 2 years, with CR rates being 40% for patients with limited disease (LD) and 10% for those with extensive disease. Patients who were classified as having extensive disease on the basis of isotope scan evidence of a single bone metastasis had survival characteristics and response rates similar to those of patient with LD. A multivariate analysis of various factors, which may influence overall survival, reveals a good-risk population to be defined as having LD and an initial performance status less than or equal to 2, with or without a single metastatic focus on bone scan. Furthermore, this risk definition fairly successfully predicted which patients had the greatest chance of achieving a CR (45%). Age less than 70 years was shown to be a significantly adverse factor on survival in these multivariate analyses after adjusting for risk. When long-term survivors (less than 24 months) were investigated by multivariate analyses, the new risk system was found to be the only significant pretreatment factor. Interestingly, sex was the next marginally influential factor on long-term survival. Future stratification by these risk categories should lead to more homogeneous subgroups for comparison of different therapeutic approaches and should provide some indication as to how much better the newer treatment program is within each risk group. PMID- 6268295 TI - Risk of brain metastasis from small cell carcinoma of the lung related to length of survival and prophylactic irradiation. AB - The problem of brain metastasis from small cell carcinoma (SCC) of the lung has been appreciated for many years, but the magnitude of the problem has been underestimated. Recent studies have shown that the risk of brain metastasis increase as survival is prolonged. Although prophylactic cranial irradiation (PCI) has reduced the frequency of brain metastases, the effect on risk estimates of differences in the periods of observation was not evaluated. From 1974 through 1979, 131 patients with SCC of the lung who had no evidence of brain metastasis by radionuclide or computerized tomographic scan were treated in the Division of Therapeutic Radiology at the Medical College of Wisconsin Affiliated Hospitals. PCI was started in 1977; 57 patients received it and 74 did not. To correct for the differing periods of observation for the two groups, an actuarial calculation of the probability of brain metastasis was used. The calculated rate of clinical failure in the brain for patients who did not receive PCI was 28% at 12 months and 58% at 24 months. The calculated failure rate of the brain for patients who received PCI was 11% at 12 and 24 months. The difference in the probability of brain metastasis between the patients who did or did not receive PCI is highly significant (P less than 0.01). The true benefit of PCI becomes apparent only when the risk of intracranial metastasis is evaluated by methods that correct for incomplete followup. PCI eliminates the progressive increase in the risk of brain metastasis that accompanies increased survival and is important to maximize the probability for cure of patients with SCC. PMID- 6268296 TI - Initial clinical studies of vindesine. AB - Vindesine, a newer vinca alkaloid derivative, underwent a phase I clinical evaluation in 68 humans with advanced, refractory malignancies. Patients received single total doses ranging from 2 to 12.5 mg, repeated every 1-2 weeks. Dose limiting myelosuppressive, gastrointestinal, and neurologic toxic effects were observed at higher doses. They consisted predominantly of neutropenia, constipation leading, on occasion, to paralytic ileus, and peripheral neuropathy. Total doses of 7.5-10 mg (equivalent to 4-5 mg/m2), repeated every 2 weeks, well tolerated. There were two partial remissions in patients with acute leukemia and prior vincristine therapy, two minor responses in patients with renal cell carcinoma, one minor response in a patient with squamous cell carcinoma of the esophagus, and one minor response in a patient with squamous cell carcinoma of the lung. Vindesine is well-tolerated by man, although it shares some of the toxic manifestations of vinblastine and vincristine. Its efficacy in some patients who were no longer responsive to vincristine therapy suggests a lack of clinical cross-resistance between these compounds. PMID- 6268297 TI - Phase II trial of cisplatin in small cell carcinoma of the lung. AB - Eighteen patients with histologically documented small cell carcinoma of the lung who had failed initial combination chemotherapy regimens were treated with single agent cisplatin in a dose of 100 mg/m2 every 3 weeks, with mannitol and fluid diuresis. Tumor regression was limited to one partial response (response rate, 6%; 95% confidence limits. 1%-27%). Significant toxic effects were gastrointestinal (severe nausea and vomiting in 12 of 14 patients) and hematologic (severe leukopenia in one patient and severe thrombocytopenia in three). The antitumor efficacy of high-dose cisplatin in heavily pretreated patients with small cell carcinoma of the lung appears to be marginal. PMID- 6268298 TI - Cefotaxime and cefazolin in the treatment of complicated urinary tract infections: a comparative study. AB - The efficacy of two dosages of cefotaxime (500 mg versus 1,000 mg) administered intramuscularly every eight hours was compared in two groups of patients with complicated urinary tract infections. No significant difference was found between the two groups. In a randomized study, a group of patients treated with 500 mg cefotaxime intramuscularly every eight hours was compared with a group of patients treated with 1,000 mg cefazolin intramuscularly every eight hours. All patients had complicated urinary tract infections and were comparable in age and underlying urologic disorders. Both drugs were well tolerated. Cure of the urinary tract infection, defined as a negative culture five to nine days after treatment, was obtained in 71% of the cefotaxime group and 60% of the cefazolin group. There was no statistical difference between these results. This study demonstrated that cefotaxime is safe and useful in the treatment of urinary tract infections. PMID- 6268299 TI - Fine structural criteria for identifying rat corticotrophs. AB - The fine structural characteristics of normal rat corticotrophs stained with anti porcine ACTH1-39 serum were studied. At the ultrastructure level immunoreactive corticotrophs appear to comprise four distinct cell types: (1) large stellate cells (Siperstein cells) containing granules (170-250 nm in diameter) arranged in a peripheral row and usually embracing an acidophil; (2) elongate spindle-shaped cells (Moriarty cells) in which the secretory granules (170-250 nm in diameter) are distributed in a row or in small clusters in the peripheral cytoplasm: (3) oval or polygonal cells filled only with small secretory granules (130-170 nm in diameter), resembling the "acidophil of small granules type" (Yoshimura et al. 1974); and (4) polygonal or stellate cells filled with secretory granules of varying diameters (180-300 nm in diameter) and occasionally embracing an acidophil. The first type is the most common, but the others are infrequent. It is concluded that the criteria of Siperstein and Miller (1970) do not necessarily include all categories of rat corticotrophs. PMID- 6268300 TI - Immunocytochemistry of luteinizing hormone-releasing hormone, vasopressin, and corticotropin following deafferentation of the basal hypothalamus of the male rat brain. AB - Luteinizing hormones-releasing hormone (LHRH), vasopressin, and corticotropin systems were examined by immunocytochemical methods in male rats 2 to 20 days after deafferentation of the basal hypothalamus. Axonal degeneration of the vasopressin system (whose perikarya lie rostral to the island) and the corticotropin system (whose perikarya lie within the island) was examined and compared with the response of the LHRH system. Vasopressin immunoreactive staining was absent in the internal zone of the median eminence 10 and 20 days after deafferentation. Disruption of the efferent projections of the opiocortin system caused the loss of almost all fiber staining outside the island by the 5th postoperative day. LHRH staining in the median eminence was modestly reduced in 5 days, considerably reduced in 10 days and negligible 20 days after deafferentation. At 10 and/or 20 days after deafferentation densely stained fibers of all three systems were observed on both sides of the cut. Invasive vasopressinergic fibers reached the lateral median eminence by the 20th postoperative day. This study reports on the response of three neuropeptide systems after complete deafferentation and demonstrates that regeneration can occur across the knife cut. PMID- 6268301 TI - Cytology of the renal appendages of Nautilus (Cephalopoda, Tetrabranchiata). AB - The renal appendages of tetrabranchiate cephalopods, Nautilus pompilius (L.) and Nautilus macromphalus (G.B. Sow.), were studied using light- and electron microscopical methods. The appendages, homologous to the renal appendages of dibranchiate cephalopods, possess in both species a folded transporting epithelium characterized by a secreting brush border and a high content of mitochondria and lysosome-like dense bodies as well as a basal labyrinth, and are separated from the blood lacunae by a multilayered lamina basalis. In the extracellular crypt-like infoldings of the epithelium, numerous concentric stratified concrements are found. The results strengthen the hypothesis that these concrements represent mineral-storage structures only found in calcium shell-supporting species within the class Cephalopoda. PMID- 6268302 TI - Reversible changes in nuclear and cell surface topography in cells exposed to collagenase and EDTA. AB - Rabbit auricular chondrocytes, SIRC cells, human fibroblasts, and HeLa cells were cultivated in vitro and the fine structural effects of various detachment procedures studied. Treatment with collagenase, trypsin, and trypsin-EDTA caused scalloping of the nuclear envelope, accumulation of phagolysosomes, and an increase in the number of cell surface extensions. Collagenase-EDTA evoked a marked deformation of the nuclei with formation of numerous deep indentations and a redistribution of heterochromatin. Similarly, the cell surface became extensively folded and the vacuolation of the cytoplasm was further increased. These changes were reversible and within 24 h the cells had regained a normal structure. In all cases, chondrocytes and SIRC cells were most prominently affected, whereas fibroblasts and HeLa cells were only slightly changed. Treatment of chondrocytes with colchicine or cytochalasin B did not produce any effects of the type mentioned above. Neither did treatment with the drugs before and during detachment with collagenase-EDTA prevent the structural modification of the cells. It therefore seems unlikely that microtubules and microfilaments are essential for this process. The structural changes occurring during detachment of cells could represent an adoptive mechanism for disposal of excessive membrane in connection with transition from a flattened to a rounded shape. PMID- 6268303 TI - A generalized technique for deletion of specific genes in large genomes: alpha gene 22 of herpes simplex virus 1 is not essential for growth. AB - We describe a general method for inactivation and deletion of genes at specific sites in large DNA genomes. In the first step of the procedure, the herpes simplex virus thymidine kinase is inserted into the genome at a specific site. In the second step, the thymidine kinase gene is desired sequences flanking the insertion site are deleted. Both steps involve recombination of the genomes with cloned chimeric fragments and utilize the available selection for or against thymidine kinase to select the desired genomes. We have applied the procedure to inactivate and to delete portions of an alpha gene of herpes simplex virus 1 specifying protein 22. The recombinant virus carrying the thymidine kinase inserted into the gene 22 and viruses exhibiting 0.1 kb and 0.7 kb deletions in the gene 22 specify new alpha polypeptides with molecular weights approximately 30% of the wild-type gene 22 product and grown normally in Vero cell cultures. PMID- 6268304 TI - Retroviruses as mutagens: insertion and excision of a nontransforming provirus alter expression of a resident transforming provirus. AB - Integration of retroviral DNA appears to occur randomly in host genomes, suggesting that retroviruses can act as insertion mutagens. We have confirmed this prediction by showing that the nontransforming retrovirus, Moloney murine leukemia virus (M-MuLV), can insert its provirus within the selectable target provided by a single provirus in a clonal rat cell line (B31) transformed by Rous sarcoma virus (RSV). Analysis of over 60 morphological revertants of M-MuLV superinfected B31 cells revealed two lines with inserts of M-MuLV proviruses within the RSV provirus but outside the transforming gene of RSV (src), at sites 0.6 and 4.0 kb from the 5' end. The inserts did not inactivate initiation of RSV RNA synthesis but did affect elongation or processing, or both, generating species with the 5' end of RSV RNA linked to sequences that presumably derive from the inserted M-MuLV DNA. In one mutant line, most of the insert was excised at low frequency, apparently by homologous recombination between repeated sequences at the ends of M-MuLV DNA. After excision, RSV src mRNA was present in normal amounts, and the cells resumed a transformed appearance. In at least four independent lines, large portions of the left end of the RSV provirus (from 1 to 6 kb) and variable amounts of leftward flanking cellular DNA (from 0.5 to 10-15 kb or more) were deleted, without nearby insertions of M-MuLV NA. The deletions removed the putative promoter for synthesis of RSV RNA; in the two cases examined, no RSV RNA was detected. These deletions may represent a second mutational effect of the superinfection by M-MuLV. PMID- 6268305 TI - DNA sequence of a mutation in the leader region of the yeast iso-1-cytochrome c mRNA. AB - We have constructed a plasmid that selectively integrates adjacent to the CYC1 locus, which determines iso-1-cytochrome c in the yeast Saccharomyces cerevisiae. Different CYC1 alleles can be conveniently recovered by digestion of total DNA from transformed strains with BgI II, a restriction endonuclease that does not cut the vector or the CYC1 gene, followed by transformation of Escherichia coli, selecting the ampicillin resistance gene carried on the original vector. This procedure was used to clone the cyc1-362 gene, which contains an alteration in front of the AUG initiation codon. The cyc1-362 mutational causes a deficiency of the iso-1-cytochrome c protein but still allows transcription of the iso-1 cytochrome c mRNA. DNA sequence analysis showed that the cyc1-362 mutation consisted of two single-base-pair substitutions, producing an A leads to G change 18 nucleotides and a G leads to A change 30 nucleotides in front of the AUG initiation codon in the mRNA. The A leads to G change at position -18 resulted in the creation of an AUG triplet, which is proximal to the normal initiation site and out of phase with the normal reading frame. The deficiency of iso-1 cytochrome c is most simply explained by assuming that translation initiates at the more proximal abnormal AUG site but not at the normal AUG site. PMID- 6268306 TI - The null cell compartment of the mouse spleen. PMID- 6268307 TI - Adoptive transfer of delayed-type hypersensitivity to Sendai virus. II. Different modes of antigen presentation determine K,D-region of I-region restriction of T cells mediating delayed-type hypersensitivity to Sendai virus. PMID- 6268308 TI - Cytotoxic cells induced in vitro by Epstein-Barr Virus antigens. PMID- 6268309 TI - 12-O- tetradecanoylphorbol- 13 acetate (TPA) treatment elevates the natural killer (NK) sensitivity of certain human lymphoid lines. PMID- 6268310 TI - [Dynamics of Epstein-Barr virus antibodies in Hodgkin's disease]. PMID- 6268311 TI - DNA modification in rat lungs following intratracheal or subcutaneous administration of 4-nitroquinoline-1-oxide, benzo[a]pyrene or 2-aminoanthracene. AB - Benzo[a]pyrene (BP)-, 2-aminoanthracene (2AA)- and 4-nitroquinoline-1-oxide (4NQO)-mediated DNA modification were investigated in rat lungs by using alkaline sucrose gradient sedimentation. The exposure-route, the physicochemical nature of the administered compound and the number of treatments were all important in determining the extent of DNA modification. 4NQO produced qualitatively similar modification whether instilled intratracheally (i.t.) as a suspension or injected subcutaneously (s.c.) in a soluble form. BP and 2AA produced no DNA alteration when injected s.c; they did, however, modify DNA sedimentation when instilled as a suspension, but not until 24 h after treatment. Furthermore, BP caused no DNA modification at any sampling time when instilled in a lipid solvent. In contrast to the DNA modification observed at 24 h after a single i.t. treatment with a BP suspension, no such alteration was detected 12 or 24 h after the last of 5 similar daily treatments. These results are discussed with respect to mechanisms of differential transport, clearance and metabolism of administered carcinogens. PMID- 6268312 TI - Release of mutagenic metabolites of benzo[a]pyrene from the perfused rat liver after inhibition of glucuronidation and sulfation by salicylamide. AB - The role of glucuronide and sulfate conjugation in presystemic inactivation of benzo[a]pyrene (BP) metabolites was investigated with rat livers perfused with BP (12 mumol). Comparisons were made between metabolite profiles and mutagenicity of medium from perfusions with and without salicylamide, a selective inhibitor of glucuronide and sulfate conjugation. After 4 h perfusion in the presence of salicylamide, certain BP metabolites (diols, quinones, phenols, and metabolites more polar than BP-9,10-diol) were significantly increased at the expense of quinones and phenols in the glucuronide fraction. Mutagenicity of medium (detected by the Ames test, using tester strains TA98 and TA100) was low in perfusion without salicylamide. Mutagenicity detected with tester strain TA98 was significantly increased in perfusions with salicylamide. Involvement of glucuronidation in BP inactivation was also observed at the subcellular level; when cofactors of glucuronidation were added to liver homogenates along with the NADPH regenerating system in the Ames test, BP mutagenicity was markedly decreased. Both the activation of BP to mutagenic metabolites and the inactivation of BP metabolites by glucuronidation was much more pronounced with liver homogenates from 3-methylcholanthrene-treated rats than with those from phenobarbital-treated animals or untreated controls. The results suggest an important role for glucuronidation and sulfation in the inactivation and elimination of polycyclic aromatic hydrocarbons. PMID- 6268313 TI - Polyhalogenated biphenyls and phenobarbital: evaluation as inducers of drug metabolizing enzymes in the sheepshead, Archosargus probatocephalus. AB - Several doses of Aroclor 1254 (polychlorinated biphenyl (PCB) mixture), Firemaster FF1 (polybrominated biphenyl (PBB) mixture), 2,2',4,4',5,5' hexabromobiphenyl (HBB), 3,3',4,4',5,5'-hexachlorobiphenyl (HCB) and phenobarbital (PB) were administered to the marine fish sheepshead (Archosargus probatocephalus). The PCB and PBB mixtures caused induction of hepatic microsomal benzo[a]pyrene hydroxylase (AHH), 7-ethoxycoumarin O-deethylase (7-EC) and 7 ethoxyresorufin O-deethylase (ERF) activities, but not benzphetamine N demethylase (BND), epoxide hydrolase (EH) or glutathione S-transferase (GSH-T) activities. This induction pattern is typical of that caused by polycyclic aromatic hydrocarbons (PAH) in fish and mammals or by tetrachlorodibenzo-p-dioxin (TCDD) in mammals. The extent of induction of AHH-activity and cytochrome P-450 content was higher when experiments were carried out in summer (water temperature 25 +/- 4 degrees C) than in winter (water temperature 11 +/- 3 degrees C). Firemaster FF1 (15 mg/kg) induced fish for at least 56 days in both summer and winter at which time the liver concentrations of PBB were in the ppm range. PCB concentrations in the ppm range have been found in fish from polluted lakes and seas, thus we may expect that environmental exposure to PCB is sufficient to induce hepatic mixed function oxidase (MFO) activities. The PCB isomer 3,3'4,4'5,5'-HCB, which induces the same spectrum of hepatic drug-metabolizing activities as TCDD and PAH in rats, had a broadly similar effect in the sheepshead. Another purified isomer, 2,2',4,4',5,5'-HBB, which induces the same enzymes as PB in rats, had no effect on drug-metabolizing activities in sheepshead. PB was also without effect on sheepshead hepatic drug-metabolizing enzymes, although a typical narcotic effect was produced in PB-treated sheepshead. Our studies provide further evidence that drug-metabolizing activities in fish liver are readily induced by chemicals like TCDD or PAH, but we fail to demonstrate induction after treatment of sheepshead with inducers of the PB type. PMID- 6268314 TI - Effect of escin on adrenocorticotropin and corticosterone levels in rat plasma. PMID- 6268315 TI - Toxicological approaches to streptothricin antibiotics. IV. Toxicity of streptothricin antibiotics to the blood. PMID- 6268316 TI - Correlation between transformation potential and inducible enzyme levels of hamster embryo cells. AB - When benzo(a)pyrene was used to evaluate the transformability of 129 hamster embryo cell preparations from pooled or individual embryos, approximately 50% of the cultures were transformable. A transformable and a non-transformable cell culture were further tested with other carcinogens (3-methylcholanthrene [MCA], benzyl chloride, ethyl-p-toluenesulfonate, 2-naphthylamine, and aflatoxin B1). The transformable culture responded to all of the carcinogens while the non transformable culture always gave negative results. Aryl hydrocarbon hydroxylase (AHH) and epoxide hydrase (EH) levels were compared in the two cell cultures using beta-naphthoflavone (BNF), benz(a)anthracene (BA), sodium phenobarbital (PB) or MCA as microsomal enzyme-inducing agents. It was found that AHH levels and the degree of induction following treatment of the cells with BNF or BA were consistently higher in the transformable than in the non-transformable cells following treatment with either BNF, BA, PB or MCA. Inducible AHH and EH levels might, therefore, be useful as predictors of the transformation potential of hamster embryo cell cultures. PMID- 6268317 TI - The effect of solvents upon the yield of revertants in the Salmonella/activation mutagenicity assay. AB - The effects of dimethylsulphoxide and acetone have been investigated in the Salmonella/activation mutagenicity assay using 2-aminoanthracene and benzo(a)pyrene as test compounds. Varying mutagenic responses were found with the solvents mutagenic responses were found with the solvents after treatment of the bacteria with 2-aminoanthracene. This was observed in two laboratories. Differences were not as evident after treatment with benzo(a)pyrene. In addition, different amounts of dimethylsulphoxide were used to dissolve amounts of dimethylsulphoxide were used to dissolve 2-aminoanthracene and varying mutagenic responses were obtained. These observations suggest that the choice and amount of solvent for individual test compounds may be critical in terms of determining a mutagenic response. PMID- 6268318 TI - Comparison of the tumor-initiating activity of 7,12-dimethylbenz[a]anthracene and benzo[a]pyrene in female SENCAR and CS-1 mice. PMID- 6268319 TI - Alpha-1-antitrypsin in intracellular inclusions of diethylnitrosamine induced hepatomas of C57BLxC3H F1 mice. AB - Six large hepatic nodules obtained 46 to 74 weeks after a single dose of diethylnitrosamine (0.625 or 1.25 micrograms/gm) in infant C57BLxC3H F1 male mice were studied to elucidate the nature of intracytoplasmic inclusions in the hepatic cells of these nodules. By light microscopy, the nodules constituted a spectrum of lesions ranging from some which were well differentiated adenomas to others which were frank carcinomas. Round or oval eosinophilic intracytoplasmic inclusions were consistently seen in the well differentiated adenomatous lesions. Some of these inclusions were PAS positive and resisted diastase digestion while others were either negative or only weakly PAS positive. By electron microscopy, they were most commonly crystalline, contained a reticulated electron dense material and were located in the distended rough endoplasmic reticulum. On immunofluorescence the inclusions showed marked specific reactivity with antisera against human alpha-1-antitrypsin. The presence of alpha-1-antitrypsin in these inclusions was further supported by the resistance of these inclusions to digestion by trypsin or papain but not by the pepsin or pronase. PMID- 6268320 TI - Potentiating effect of benzo[a]pyrene and caffeine on Friend viral leukemogenesis. AB - The effect of exposing mice to both a chemical carcinogen and leukemia virus with and without an inhibitor of DNA repair were compared. The data indicated that benzo[a]pyrene (BP) could exert a potentiating effect of Friend viral leukemogenesis in mice, which was dependent on the relative times of administration of the chemical and virus. The addition of caffeine as an inhibitor of DNA repair further enhanced the potentiating effect of BP on the leukemia, but in the absence of BP, caffeine showed no carcinogenic effect either when given alone or in conjunction with Friend leukemia virus. PMID- 6268322 TI - The involvement of DNA topoisomerases in DNA repair and mutagenesis. PMID- 6268321 TI - Effect of dietary wheat bran and dehydrated citrus fiber on 3,2'-dimethyl-4 aminobiphenyl-induced intestinal carcinogenesis in F344 rats. AB - The effect of dietary wheat bran and dehydrated citrus fiber on 3,2'-dimethyl-4 aminobiphenyl (DMAB)-induced colon and small intestinal carcinogenesis was studied in male F344 rats. Weanling rats were fed semipurified diets containing 5% alphacel, 5% alphacel + 15% wheat bran or 5% alphacel + 15% citrus fiber. At 7 weeks of age, all animals, except vehicle-treated controls, received weekly s.c. injections of 50 mg DMAB/kg body weight for 20 weeks. The DMAB- or vehicle treated groups were autopsied 20 weeks after the last injection of DMAB. The animals fed the wheat bran diet and treated with DMAB had a lower incidence (number of animals with tumors) and multiplicity (number of tumors/tumor-bearing animal) of colon and small intestinal tumors than did those fed the control diet and treated with DMAB. Animals fed the diet containing citrus fiber developed fewer small intestinal tumors (incidence and multiplicity) than did the rats fed the control diet; the number of adenocarcinomas was reduced in rats fed the citrus fiber diet. This study thus indicates that diets containing wheat bran and citrus fiber reduce the risk for DMAB-induced intestinal cancer and that the protection against colon cancer depends on the type of fiber. PMID- 6268323 TI - Comparison of the metabolism of benzo[a]pyrene and its activation to biologically active metabolites by low-passage hamster and rat embryo cells. PMID- 6268324 TI - Mesotheliomas in rats following inoculation with acid-leached chrysotile asbestos and other mineral fibres. AB - The carcinogenicity of untreated UICC chrysotile A, of acid (oxalic and hydrochloric)-leached UICC chrysotile A, of crocidolite and of JM 104 glass fibres has been studied by intrapleural injection into rats. This experiment, carried out on 304 animals, demonstrated that when more than 80% of the Mg had been leached from chrysotile fibres by either hydrochloric or oxalic acid, the proportion of pleural mesotheliomas was either nil or dramatically lower than that obtained with untreated chrysotile. The carcinogenic effect of crocidolite was higher than that of 43.7% oxalic acid-leached chrysotile. The proportion of mesotheliomas observed in animals injected with JM 104 glass fibres was similar to that in animals injected with fibres from which 63.8% had been leached with oxalic acid. These results indicate that with regard to the induction of pleural carcinogenicity by chrysotile fibres, not only size characteristics but also parameters such as chemical composition and physiochemical properties must intervene. PMID- 6268325 TI - Carcinogenicity of the environmental pollutants cyclopenteno-[cd]pyrene and cyclopentano[cd]pyrene in mouse skin. AB - Cyclopenteno[cd]pyrene (CPEP) is a widespread environmental pollutant. This hydrocarbon and its 3,4-dihydro derivative, cyclopentano[cd]pyrene (CPAP), were tested on skin in a two-stage initiation-promotion experiment in CD-1 mice and by repeated application in Swiss mice. The biological effect of CPEP and CPAP was compared to that of benzo[a]-pyrene (BP). Nine-week-old female CD-1 mice in groups of 30 were treated every other day over a 20-day period at mini-dose levels of 0.18, 0.06 and 0.02 mumol of CPEP or CPAP in acetone. One group was treated with BP at the low mini-dose level. Initiation was followed by twice weekly application of tetradecanoyl phorbol acetate for 40 weeks. In the second experiments, nine-week-old female Swiss mice in groups of 30 were treated at dose levels of 1.8, 0.6 and 0.2 mumol CPEP or CPAP in acetone twice weekly for 30 weeks. One group was treated with BP at the low dose. CPAP was virtually inactive in both studies. In the initiation-promotion experiment CPEP was inactive at the low dose level, whereas BP exhibited significant tumorigenicity. At the medium and high doses CPEP showed weak, but statistically insignificant, tumorigenic activity. Repeated application of CPEP at the high, medium and low doses resulted in tumor incidences of 23, 37 and 57%, respectively. This reverse dose-response may be due to the relatively high cytotoxicity of CPEP, BP, which was compared to CPEP at the low dose, elicited tumors in 100% of the mice. Most of the CPEP induced neoplasms were malignant and some metastasized to lungs and lymph nodes. The inactivity of CPAP suggests the carcinogenicity of CPEP is probably due to formation of the ultimate metabolite CPEP 3,4-oxide. In view of the abundance of CPEP in environmental and occupational pollutants, its moderately potent carcinogenicity may represent a potential health hazard. PMID- 6268326 TI - Carcinogen-mediated induction of SV40 DNA synthesis in SV40 transformed Chinese hamster embryo cells. AB - Exposure of SV40-transformed Chinese hamster embryo cells (line CO50) to a series of physical and chemical carcinogens (including activation-dependent and activation-independent varieties) resulted in the induction of viral DNA synthesis. The carcinogen mediated amplification of SV40 DNA was demonstrated by a highly sensitive in situ hybridization procedure for the detection of cells synthesizing SV40 DNA. Treatment of CO50 cells with an inhibitor of polycyclic hydrocarbon metabolism (7,8-benzoflavone) prior to the application of benzo[a]pyrene or 7,12-dimethylbenz[a]anthracene prevented the induction of SV40 DNA synthesis, indicating that the induction depends upon the metabolic activation of these compounds. Non-carcinogenic hydrocarbons were inactive under this assay. Two different protocols for determining the inducing potential of a compound are presented. The properties of this test and its possible use as a short-term assay for potential carcinogens is discussed. The possibility that the induction of SV40 DNA synthesis is a reflection of a general gene amplification phenomenon mediated by carcinogens is discussed. PMID- 6268327 TI - Sensitivity of normal and transformed rat liver epithelial cells to benzo[a]pyrene toxicity. AB - A strain of rat liver epithelial cells (LP), a clone of LP (C3) and a series of transformed lines derived from these cell strains, were examined for their sensitivity to the toxic effects of benzo[a]pyrene (BP). Both LP and C3 were sensitive to BP and within the series of transformed cell lines, sensitivity to BP was positively related to the extent of differentiation of the tumours each line formed in vivo. All the cell types were able to take up BP and there appeared to be a relationship between the sensitivity of a given cell type to BP, and the amount of BP it metabolised. The binding of BP to the DNA was low in all the cell types examined. PMID- 6268328 TI - The uptake and release of benzo[a]pyrene and benzo[e]pyrene in vitro by Syrian hamster embryo cells as a function of serum concentration. AB - A quantitative study on the in vitro uptake of benzo[a]pyrene (B[a]P) and benzo[e]pyrene (B[e]P) by Syrian hamster embryo cells and the induction of sister chromatid exchange (SCE) has been carried out. The amounts of B[a]P and B[e]P taken up by the cells decreases as does the induction of SCEs by B[a]P when the concentration of serum in the culture medium increases. It appears that serum prevents (B[a]P or B[e]P uptake. We have observed no significant differences between the two hydrocarbons regarding uptake by cells; chromatographic results show however that B[a]P is metabolized by these cells, while B[e]P is not. Our results suggest that serum inhibits B[a]P and B[e]P uptake and hence decreases the number of SCEs. PMID- 6268329 TI - Induction of morphological transformation of hamster embryo cells in vitro by diphenylnitrosamine. PMID- 6268330 TI - Dehydroepiandrosterone and 16 alpha-bromo-epiandrosterone: inhibitors of Epstein Barr virus-induced transformation of human lymphocytes. AB - Dehydroepiandrosterone (DHEA), a major adrenal secretory product in men and women, is a potent inhibitor of mammalian glucose-6-phosphate dehydrogenase (G6PDH). Long-term treatment with this steroid has previously been found to suppress spontaneous breast cancer development in C3H mice. DHEA is now shown to inhibit Epstein-Barr virus (EBV)-induced morphologic transformation and stimulation of DNA synthesis in human lymphocytes. 16 alpha-Br-epiandrosterone, a DHEA analog that is about 60 times as potent as DHEA as an inhibitor of G6PDH, is much more effective as an inhibitor of EBV-induced transformation. PMID- 6268331 TI - Adrenergic responses of gracilis arteries removed during hemorrhagic hypotension and shock. AB - Previous studies suggest that the gracilis vasculature responds to hypovolemic hypotension by constriction followed by vasodilation [Circ Shock 4:327, 1977; Circ Shock 6:43, 1979]. The objectives of the present study were to determine if the effective vascular smooth muscle population and/or adrenergic innervation density varies as the dog moves from compensatory into decompensatory shock. Gracilis arteries with adventitia intact were resected during four different stages of shock and compared to nonshocked vessels. All vessels were placed in a tissue chamber filled with warm (37 degrees C) Krebs-Henseleit solution and bubbled with 95% O2 and 5% CO2. Norepinephrine (NE) dose-response and periarterial electrical stimulation (ES) frequency-response studies were conducted. The maximum response to NE was not altered from control during either compensatory or decompensatory shock, but the maximum response to ES fell during compensatory and early decompensatory hypovolemic hypotension. The sensitivity of the innervated alpha receptors, as measured by the ES necessary to obtain a 50% maximal response (ES50), also fell below control during early decompensatory hypotension but returned to control values during early and late normovolemic shock, even though the sensitivity of the alpha receptors to NE (ED50) increased. These data support the suggestion that the skeletal muscle vascular decompensation occurring as a consequence of hemorrhage may be caused by a neuromuscular transmission failure. PMID- 6268332 TI - Hormone receptors of the baboon cardiovascular system. Biochemical characterization of myocardial cytoplasmic androgen receptors. AB - Using the synthetic androgen R1881 (17 beta-hydroxy-17alpha-methyl-estra-4, 9, 11 trien-3-one) as probe, we identified cytoplasmic androgen receptors in baboon myocardium. The relative binding affinity of selected steroids for the androgen receptor was R1881, 100%; 5alpha-dihydrotestosterone, 32.6%; testosterone, 29.6%, progesterone, 7.2%; R5020, 1.0%; and estradiol-17beta, 5.8%. The androgen receptor migrated on low ionic strength linear sucrose density gradients as a macromolecule with a sedimentation coefficient of 8.5S. Saturation analysis performed at 2 degrees C (available sites) showed that the androgen receptor content of baboon myocardial cytoplasmic extracts was 5.9 +/- 1.4 fmol/mg protein and that the dissociation constant for R1881 was 1.16 +/- 0.30 nM. These cytoplasmic androgen receptors are indicated to be physiologically functional by previous autoradiographic studies (McGill et al., 1980; McGill and Sheridan, 1981) that showed localization of radioisotope in nuclei of myocardial fibers following injection of baboons with 5 alpha-dihydrotestosterone. PMID- 6268333 TI - The effect of acetylcholine, ischemia, and anoxia on rat heart purine cyclic nucleotides and contractility. PMID- 6268334 TI - George E. Brown memorial lecture. Local modulation of adrenergic neurotransmission. AB - The cardiovascular reflexes, by regulating the traffic in the sympathetic nerves, govern the amount of norepinephrine released from the nerve endings. However, the final adjustments in the amount of neurotransmitter available to activate the beta 1 receptors in the heart and the alpha receptors in the blood vessels take place at the sympathetic neuroeffector junction. Thus, a decrease in pH, hyperosmolarity, moderate increases in the concentration of K+ ion, adenosine and adenine nucleotides depress the release of norepinephrine at any given level of sympathetic nerve activity. These metabolic changes, which occur in active tissues, and in particular in adenosine, have been proposed as mediators of the accompanying local hyperemia. In addition, they apparently facilitate this local dilatation by disconnecting the blood vessels in the active tissues from sympathetic control. Acetylcholine, histamine and 5-hydroxytryptamine are present in and around certain blood vessels and can activate specific receptors on the prejunctional fibers and cause vasodilatation by reducing the output of neutrotransmitter. Some of the norepinephrine released into the synaptic cleft may depress its continued release by activating prejunctional alpha receptors. In contrast, angiotensin II, by a local action on the nerve endings, can augment the release of transmitter. Decreases in local temperature reduce transmitter release but augment the affinity of the postjunctional alpha receptors for norepinephrine. The role of these local events at the neuroeffector junction, their physiologic significance and potential clinical importance are discussed in this review. PMID- 6268335 TI - Chemical radiation sensitizers and protectors: recent developments. PMID- 6268336 TI - B lymphocytopenia in infectious mononucleosis. AB - Changes in lymphocyte surface markers during Epstein-Barr virus (EBV) associated infectious mononucleosis (IM) were re-examined because (1) these changes may provide information about host immune restraints to the initiation of a malignant process and (2) problems in the identification of B lymphocytes were often not appreciated in previous observations. An acute and transient reduction of IgM- and IgD-bearing B lymphocytes in the peripheral blood of these patients was demonstrated. The numbers of cells bearing Fc receptors and T lymphocytes were less consistently altered. It is hypothesized that the reduction of IgM- and IgD bearing cells is caused by interference with the production of these cells or alternately their elimination by the virus or activated T lymphocytes. PMID- 6268337 TI - The effects of an ECF-A and formyl methionyl chemotactic peptides on oxidative metabolism of human eosinophils and neutrophils. AB - An ECF-A tetrapeptide (Val-Gly-Ser-Glu) and the synthetic bacterial analogue, formyl Met-Leu-Phe (agents previously recognized to be chemotactic and to enhance complement receptors on human eosinophils and neutrophils), were tested for their capacity to evoke a spontaneous burst of light emission (chemiluminescence), and to affect oxygen-consuming reactions induced by contact with serum-treated zymosan (STZ). Superoxide anion (O-2) production by neutrophils induced by STZ was significantly enhanced in both a time- and concentration-dependent fashion by F-Met-Leu-Phe, and to a lesser extent, by F-Met-Met-Phe. The dipeptide F-Met-Phe and unformylated Met-Leu-Phe were inactive. In addition, significant enhancement of eosinophil O-2 generation, by the valyl- ECF-A tetrapeptide was demonstrable and, in addition, this peptide appeared to have an inhibitory effect on neutrophil superoxide anion generation. Eosinophils and neutrophils both produced a burst of chemiluminescence when treated with F-Met-Leu-Phe. With both cell types the magnitude of the responses was similar although with eosinophils peak activity occurred within 60 sec as compared to 2-6 min for neutrophils. No chemiluminescent response was achieved with the valyl- ECF-A tetrapeptide using either cell type. These experiments (1) suggest that ECF-A and formyl methionyl peptides amplify reactions associated with the respiratory burst of eosinophils and neutrophils respectively, and (2) support the view that the generally greater metabolic activity of eosinophils may be related to the special role that this cell may play in the killing of helminthic parasites. PMID- 6268338 TI - Enhanced cAMP production by activated human Fc-IgG receptor positive T-cell subpopulations. PMID- 6268340 TI - Human B-lymphocyte subpopulations. I. Differentiation of density-separated B lymphocytes. PMID- 6268339 TI - Metabolic abnormalities of human adenosine deaminase deficiency reproduced in the mouse by 2'-deoxycoformycin, and adenosine deaminase inhibitor. PMID- 6268341 TI - Characterization of physically different human T-cell subsets with monoclonal antibodies and biochemical markers. PMID- 6268342 TI - Antiviral immunity in chronic glomerulonephritis. AB - Antiviral activity was evaluated in sera from 65 patients with chronic glomerulonephritis (GN), 58 patients with SLE and 59 healthy controls. Antibodies to influenza A2 and B, and parainfluenza I-II-III viruses occurred much more frequently in GN than in healthy controls. Geometric mean antibody titers to measles, influenza A2 and B, and parainfluenza I-II-III were found to be elevated. The frequency of antiviral antibodies and their level in GN patients were similar to those in SLE patients. Detection of increased antiviral activity in sera of patients with chronic GN extends the range of diseases where persistent latent viral infection may be relevant. PMID- 6268343 TI - The diagnosis of renal osteodystrophy: a comparison of Technetium-99m pyrophosphate bone scintigraphy with other techniques. AB - In order to determine the place of Technetium-99m-pyrophosphate bone scintigraphy in the assessment of renal osteodystrophy, 17 patients with chronic renal failure requiring hemodialysis underwent bone scans and these were compared to results of biochemical, radiological and histologic studies. Bone histology was abnormal in all patients with most having evidence of osteomalacia and hyperparathyroid bone disease. Using semi-quantitative scan scores and regional bone-standard ratios, isotope uptake was increased in 16 patients, while 15 had elevated alkaline phosphatase levels and 7 had X-ray changes. An osteoid-osteoclast index combining histological osteomalacia and hyperparathyroid disease was derived and was found to correlate more closely with alkaline phosphatase and parathyroid hormone levels than with scan parameters. It was concluded that bone scans did not provide therapeutically useful information that could not be obtained from biochemical and radiological studies. It appeared that only bone histology could differentiate osteomalacia and hyperparathyroid bone disease. PMID- 6268344 TI - New knowledge on the origin, function and fate of osteoclasts. AB - The most recent findings on the origin, life-span and fate of the osteoclast can be summarized as follows. Osteoclasts originate from progenitor, mononuclear, lymphoid cells which reach the bone surface through the bloodstream. Osteoclasts resorb bone by secreting lysosomal enzymes and procollagenase in the osteoclast bone interspace. The organic components of the matrix (first interfibrillary substance, then collagen fibrils) are digested in the extracellular space. Dislodged crystals and residual organic constituents are then phagocytosed and collected in cytoplasmic vacuoles where they are completely solubilized. The ruffled border and the adjacent "clear" zone constitute the resorbing apparatus, whose development is roughly proportional to osteoclast activity. Osteoclast nuclei are continuously incorporated and shed, so that individual cells are continuously renewed. This makes the life-span of the osteoclast extremely difficult to determine. The life of each individual osteoclast might theoretically continue as long as the stimulus to resorption persists and sufficient bone matrix is available. Primary abnormalities of the osteoclasts can induce pathologic skeletal changes, as in the case of osteopetrosis and Paget's disease of bone. Conversely, skeletal abnormalities may damage osteoclasts, as in the case of lead intoxication. When this happens, osteoclasts are essentially characterized by an underdeveloped ruffled border, pyknotic nuclei, detachment from the bone matrix and, finally, shrinkage and fragmentation. It is not yet known whether these changes only occur in pathologic conditions, or whether they are the alterations which lead senescent osteoclasts to death even in normal bone. PMID- 6268345 TI - Detection of a pedunculated right atrial tumor by radionuclide imaging. PMID- 6268346 TI - Football head and neck injuries--an update. AB - In the last 5 years there has been a dramatic decrease in the deaths directly related to football participation. The incidence of serious spinal cord injuries, however, appears to be increasing. The number of quadriplegic athletes varies from an estimated 1 per 7,000 to 1 per 58,000 participants per year in different areas of the country. The majority of catastrophic head and neck injuries occurs while tackling or blocking, and defensive players are much more liable to sustain these injuries than offensive players. In addition to permanent and irreversible spinal cord damage, football players may suffer spinal concussions as well as spinal contusions. The latter may be manifested by severe burning paresthesias and dysesthesias in the extremities as the only symptoms. Furthermore, fracture dislocations with ligamentous tears may be present in this syndrome, with no complaint of cervical pain. Adequate preconditioning and strengthening of the head and neck musculature prior to football participation are essential for the prevention of catastrophic head and neck injury. Furthermore, proper blocking and tackling techniques must be taught, and such punishing maneuvers as spearing, goring, and butt-blocking and tackling must be eliminated. Arbitrarily, most physicians discourage further football participation if an athlete has suffered three cerebral concussions. Strong consideration must be given, however, not only to the number and severity of the concussion, but also to any CAT scan evidence of cerebral edema, contusion, or hemorrhage. With this incredibly sensitive diagnostic tool, one concussion, which is associated with radiographic evidence of structural brain damage, may be enough to strongly discourage or forbid further football participation. PMID- 6268347 TI - Hormonal responses to long-term converting enzyme inhibition in hypertensive patients. AB - Captopril was given alone and in combination with diuretics to 49 patients with hypertension for 1 to 12 mol Within 2 mo blood pressure reduction correlated with pretreatment plasma renin activity and response to the infusion of angiotensin II antagonist, but these effects were not present at 4 mo. Plasma and urinary aldosterone were suppressed but serum converting enzyme activity, plasma bradykinin, kallikren, and prostaglandins (E and F) were in the normal range effect of captopril. Despite sustained reduction of blood pressure, plasma catecholamines were not elevated and urinary catecholamines were suppressed in patients on captopril alone. It is concluded that another mechanism, such as enhancement of renal or local kinin-prostaglandin system, as well as suppression of the renin-angiotensin-aldosterone system may be involved in the long-term efficacy of captopril. Sympathetic activity may also be depressed and contribute to the hypotensive effect. PMID- 6268348 TI - Colorado physicians and THC. PMID- 6268349 TI - [Metabolic impairment of the hepatocyte in pregnancy: prevention and therapy with a membrane-stabilizing drug]. PMID- 6268350 TI - Neuropathy associated with chronic low level exposure to n-hexane. AB - Concentrations of n-hexane greater than the threshold limit value (TLV) of 500 ppm are known to produce peripheral neuropathy. This report describes the case of a worker who developed peripheral neuropathy, with a histologic pattern characteristic of n-hexane toxicity, after chronic on-the-job exposure to n hexane at concentrations less than 450 ppm. We suggest that the current TLV for n hexane be reevaluated. PMID- 6268352 TI - Behavioral pharmacology of tetrahydrocannabinol convulsions in rabbits. PMID- 6268351 TI - Detection and quantitation of cannabinoids in biological fluids: specificity and kinetics after smoking. AB - A procedure for the quantitation and detection of cannabinoids in biological fluids (plasma and urine) is described. This method is based on isotopic derivatization and double labeling. delta 9-Tetrahydrocannabinol and two of its metabolites (11-hydroxy-delta 9-THC and 8-beta-hydroxy-delta 9-THC) can be detected and measured in plasma or urine. The use of TLC enables specific separation of cannabinoids. The sensitivity of detection (4 ng/mL) is compatible with cannabinoid kinetics. The procedure can be applied to routine measurements and pharmacokinetic studies. PMID- 6268353 TI - Herpesvirus hominus (herpes simplex virus). PMID- 6268354 TI - Decreased serum angiotensin converting enzyme in adult respiratory distress syndrome associated with sepsis: a preliminary report. AB - Serum angiotensin converting enzyme (ACE) levels were obtained in 24 control patients who were critically ill, in 11 patients with cardiogenic pulmonary edema, in 8 patients with status postcardiopulmonary bypass, and in 12 patients with adult respiratory distress syndrome (ARDS). Mean values in cardiogenic pulmonary edema (24.3 +/- 3.9 SD) in cardiopulmonary bypass (19.5 +/- 3.1) and in patients with ARDS and no sepsis (n = 7, 19.0 +/- 5.5) were not significantly different from controls (20.7 +/- 2.8). In contrast, patients with ARDS and sepsis had markedly decreased serum ACE levels which fell outside of control range (n = 5, 8.6 +/- 2.3). The authors speculate that decreased ACE levels in the combination of sepsis and ARDS are due to the presence of circulating inhibitors of ACE. The finding of decreased serum ACE can be of potential clinical usefulness by raising the possibility of sepsis as the etiology of ARDS before results of blood cultures are available. PMID- 6268356 TI - Breast cancer screening. PMID- 6268355 TI - CT in the evaluation of pediatric abdominal abnormalities. AB - Space does not permit a discussion of the use of CT in the pelvis and chest, but obviously conditions such as lymphoma may involve these areas as well as the abdomen while pelvic masses may commonly present as abdominal abnormalities. In this review the author has tried to summarize the experiences of other and to combine this with his 4-year experience using an integrated imaging approach to arrive at some preliminary conclusions as to how CT may best be used in the care of children with abdominal abnormalities. As technology improves and experience widens, present thought and indications will undoubtedly be altered and probably be expanded. Even at this early stage it seems obvious to the author that CT should have great impact on traditional ways of studying abdominal pathology and that if properly used, it will result in better patients care at less cost in time and money to society and less trauma to the afflicted child. PMID- 6268357 TI - Degenerative disorders of the cerebellum studied by computerized tomography. AB - A review of our cases as well as of the clinical and radiological literature indicates that, in instances of cerebellar degeneration, certain CT patterns are constant. The most reliable are: 1. Prominence of cerebellar sulci. These are usually not seen normally, except for some of the primary fissures; in atrophy the sulci are easily distinguished. 2. Enlargement of the superior cerebellar cistern and vermian cistern. 3. Enlargement of the cerebellopontine cistern. This cistern, which is also referred to as the cerebellopontine angle cistern and as the lateral recess of the cerebellopontine cisterns, is particularly prominent when the middle cerebellar peduncle is significantly involved. 4. Enlargement of the pre-pontine cistern, which occurs primarily with involvement of the pons. 5. The fourth ventricle may be enlarged, particularly in conditions where the midline cerebellar nuclei are affected. However, the enlargement of the fourth alone does not have to be associated with a pathological process. As previously established with pneumoencephalographic studies, the size of the fourth ventricle can be variable (14). Likewise, enlargement of the cisterna magna is not usually associated with any pathological condition of the cerebellum (15). PMID- 6268358 TI - Ultrasonographic findings of normal and pathologic placenta and umbilical cord. PMID- 6268360 TI - Radiologic evaluation of renal cystic disease in children. PMID- 6268359 TI - Nuclear medicine: a new tool in the diagnosis of cardiac disease. PMID- 6268361 TI - Phosphorylation-dephosphorylation cycles and the regulation of fuel selection in mammals. PMID- 6268362 TI - Aldolase and fructose bisphosphatase: key enzymes in the control of gluconeogenesis and glycolysis. PMID- 6268363 TI - Formation and utilization of PEP in microbial carbohydrate transport. PMID- 6268364 TI - The cycling of oxygen through intermediates in the cytochrome oxidase-oxygen reaction. PMID- 6268365 TI - Energy cycles in health and disease. PMID- 6268367 TI - Structure and hormonal regulation of the ovalbumin gene cluster. PMID- 6268366 TI - Phosphorylation and dephosphorylation of glycogen phosphorylase: a prototype for reversible covalent enzyme modification. PMID- 6268368 TI - Catabolite repression in yeast: mediation by cAMP. PMID- 6268369 TI - Facial swelling in a middle-aged man. PMID- 6268370 TI - Serum angiotensin-converting enzyme levels in patients with pigeon-breeder's disease. AB - The serum concentration of angiotensin-converting enzyme is frequently elevated in individuals with active sarcoidosis. The enzyme is presumably actively synthesized by the epithelioid and giant cells of the granuloma. Hypersensitivity pneumonitis, resulting from the inhalation of antigens from pigeons by susceptible individuals, is associated with the development of a granulomatous interstitial and alveolar infiltrate in the pulmonary parenchyma. Because the clinical and pathologic presentation may mimic that of sarcoidosis, we compared the serum levels of angiotensin-converting enzyme in these two diseases. The concentration of angiotensin-converting enzyme is not elevated in individuals with active hypersensitivity pneumonitis, in contrast to its frequent elevation in sarcoidosis. We suggest that the granulomatous response in hypersensitivity pneumonitis may differ at a biochemical level from that of sarcoidosis, since the synthesis of angiotensin-converting enzyme does not appear to be increased. PMID- 6268371 TI - Distribution of spacer length classes and the intervening sequence among different nucleolus organizers in Drosophila hydei. AB - Drosophila hydei rRNA genes from different chromosomes and from different stocks have been studied by restriction enzyme analysis. In DNA from wild-type females, about half of the X chromosomal rRNA genes are interrupted by an intervening sequence within the 28S coding region. In contrast to D. melanogaster, the intervening sequences belong to a single size class of 6.0 kb. Although there are two nucleolus organizers on the Y chromosome, genes containing the intervening sequence seem to be restricted to the X chromosome. -- As shown in four cloned rDNA fragments, the nontranscribed spacers differ in length by having varying numbers of a 242 base pair sequence located in tandem in the right section of the spacer. In genomic rDNA, the spacers also differ in length by a regular 0.25 kb interval. Spacers with between 5 and 15 subrepeats occur frequently within the X and Y chromosomal nucleolus organizers in different D. hydei stocks; shorter and longer spacers are also present but are relatively rare. -- Although each genotype is characterized by different frequencies of some spacer classes, the prominent spacer length heterogeneity pattern is similar among the different nucleolus organizers and, therefore, seems to be conserved during evolution. PMID- 6268372 TI - Restriction enzyme analysis of the germ line limited DNA of Ascaris suum. AB - The germ line limited DNA of Ascaris suum was isolated from sperm and testis as a satellite DNA component in Hoechst 33 258 -- CsCl gradients. Employing restriction enzyme analysis, we show that the germ line limited DNA is composed entirely of two families of tandemly repeated sequences, one repeat unit is 125 bp, and the other 131 bp long. The total appr. 5 x 10(5) copies of the two families are physically separated from each other (segmental arrangement). Several repeat unit variants within both families could be detected. The copies of sequence variants are arranged in tandem (subsegmental arrangement). Reassociation and hybridization experiments revealed similar sequences of the two repeat units. The archaeotypic core sequence of both repeat units is probably a tetranucleotide which shows a 'theme and variation' pattern. During chromatin diminution in the presoma cells the satellite DNA is eliminated from the chromosomes. However, a limited number of tandemly repeated copies of both kinds of repeat units could be detected in the soma genome using radioactive probes of both repeat units in Southern blots of muscle and intestine of adult animals. The tandem arrangement and the hierarchical pattern of restriction sites throughout different subfamilies supports the model of successive segmental amplification events during the evolution of the germ line limited DNA. Since the germ line limited satellite DNA is exclusively located at the ends of the chromosomes, a fold back structure for the telomeric DNA sequences is proposed which might have generated this DNA. PMID- 6268373 TI - Restriction enzyme analysis of a highly diverged satellite DNA from Drosophila nasutoides. AB - The satellite II DNA of Drosophila nasutoides is a highly diverged repetitive DNA, showing about 17% base changes between repeat units (Cordeiro-Stone and Lee, 1976). This DNA is cleaved by four different restriction enzymes to produce multimeric fragmentation patterns, indicating that their restriction sites are regularly arranged. Moreover, all four enzymes produce identical fragment lengths, the size of a monomer being 96 base pairs. Such multimeric patterns are expected for a diverged repetitive DNA, since many restriction sequences could have undergone changes during sequence divergence. Further restriction analyses of this DNA by double digestions and cloning reveal that there are three different sequences in satellite II DNA with respect to the presence and the arrangement of various restriction sites (Fig. 7). As an example, one sequence contains many EcoRI sites and fewer HinfI sites (20% of EcoRI sites), which are arranged regularly. These observations suggest that satellite II DNA of D. nasutoides might have evolved through different modes of sequence divergence. PMID- 6268374 TI - Fine structure and cytochemistry of the mammalian pars intermedia. AB - Various cytophysiological aspects of the pars intermedia of the pituitary are discussed. Cells containing melanocyte-stimulating hormone (MSH) have been studied under normal and experimental conditions. They react to variations in ionic equilibrium, but without any clear correlation with natraemia and osmotic blood pressure. The MSH-cell stimulation in hypernatraemic mice, which is not inhibited by bromocriptine, seems more specific than the stimulation in hyponatraemic mice, which is blocked by bromocriptine. The existence of a corticotropic cell system has been clearly demonstrated in the mouse (where it is particularly obvious), in the rat and in the cat but its significance is not clear. Although very poorly vascularized, the pars intermedia is rapidly invaded by tracer protein (horseradish peroxidase) injected either intravenously or intracerebroventricularly. The hypophysial cleft rapidly stores the tracer which can be resorbed by macrophagic epithelial cells lying free in the colloid contained in the cleft. Horseradish peroxidase lingers in the pars intermedia but is rapidly eliminated from the other hypophysial lobes after intraventricular (third ventricle) injection. Diffuse innervation of the pars intermedia applies to both glandular (MSH and ACTH) and non-glandular (epithelial and stellate) cells. While aminergic innervation of the pars intermedia is obvious, cholinergic innervation has not been demonstrated ultrastructurally or histochemically. Peptidergic fibres only occasionally penetrate marginal areas of the pars intermedia and seldom establish synaptic contacts with glandular cells. A specific relationship might exist between the pars intermedia and oxytocin fibres in view of the marginal distribution of the latter in the neural lobe. Numerous stellate cells of the pars intermedia react intensely with antiserum to gliofibrillar acid protein, indicating their astrocyte nature, which reinforces the idea of an analogy between the folliculo-stellate system of the hypophysis and the glial cells. PMID- 6268375 TI - Structure and chemistry of the peptide hormones of the intermediate lobe. AB - The peptide hormones of the intermediate lobe are derived from a common precursor protein and are therefore biogenetically and structurally related. They represent a group of linear, flexible peptides which elicit a variety of physiological response. Structure-activity studies have shown that different segments of adjacent amino acid residues have a specific function (e.g. address, message, potentiation) in the interaction of each of these hormones with its receptor(s). This kind of organization of hormonal information is called sychnologic; it is the basic for the pleiotropic action of the opiomelanocortin peptides, i.e. the ability of related peptides to interact with different types of receptors in different target cells. Labelled peptide hormones with radioactive, fluorescent, or photolabile groups at defined sites are a prerequisite for studying hormone receptor interaction. Multi-labelled derivatives of alpha-MSH are suitable for degradation and intracellular incorporation studies. Photoaffinity labelling of melanophore receptors with azidophenyl-containing analogues of alpha-MSH produces an irreversible stimulation of pigment cells. Covalent conjugates between peptide hormone receptors. These conjugates exhibit remarkable properties such as superpotency, strongly enhanced receptor affinity and prolonged action. PMID- 6268376 TI - Nature and control of peptide release from the pars intermedia. AB - Pro-opiocortin, the precursor of ACTH, LPH and gamma-MSH, is biosynthesized in both the cells of the pars intermedia and the corticotrophs of the pars distalis. In the pars distalis its processing does not vary significantly from species to species whereas in the pars intermedia large differences occur. The release of ACTH, beta-LPH and pro-gamma-MSH from the corticotrophs is under common positive control by hypothalamic corticotropin-releasing factor (CRF) and the nature of the peptides remains unchanged when they are secreted. The release of all five pars intermedia peptides that we have measured in vitro appears to be under tonic dopaminergic inhibition. The secreted peptides have also been identified chromatographically. The lack of unequivocal physiological function in the periphery, the diversity of the pars intermedia peptides and this common control mechanism tend to preclude a simple endocrine role for the pars intermedia. The neural effects of MSH and endorphin are well documented and specific neuronal uptake therefore cannot by dismissed. The absence of pars intermedia in the adult human pituitary suggests that such a site of synthesis of these peptides plays a minor role in learning and behaviour in a species (such as Homo sapiens) that has a highly evolved intelligence and may, instead, need to synthesize the peptides only in the brain. PMID- 6268377 TI - The pars intermedia and the fetal pituitary-adrenal axis. AB - The increased production of cortisol by the fetal adrenal gland at term acts as the trigger for parturition in some species. The fetal pituitary controls fetal adrenal function. However, ACTH is only one of a family of closely related peptides which derive from a common precursor and we have shown that although ACTH is the dominant form in the adult pituitary, the expression of the "family trees' is altered in the fetus. In the sheep, it is large-molecular-weight precursors and, in the primate, the smaller peptides such as alpha-MSH, CLIP, beta-MSH and beta-endorphin that predominate in fetal life and which may be responsible for fetal adrenal function. It is still unclear what causes the developmental change in the ACTH "family tree'. Since it may result from a change in pituitary function - from the peptides of the pars intermedia, in the fetus, to those of pars anterior, in the adult - we have studied these two lobes separately in pituitaries taken from adult and fetal sheep and monkeys. Our preliminary results suggest that the change may occur in the neurointermediate lobe in the primate, but that in the sheep the developmental changes occur in the anterior lobe. PMID- 6268378 TI - Functions of alpha-melanotropin and other opiomelanocortin peptides in labour, intrauterine growth and brain development. AB - In a number of animals and in humans, factors from the fetal hypothalamus function in intrauterine growth, in labour and in brain development. Peptides of the opiomelanocortin family are produced by the pituitary, brain and placenta and are probably involved in these developmental processes. In the rat, alpha-MSH stimulates fetal growth, protein synthesis, wound healing and liver regeneration and it reduces periosteal bone resorption. In chick embryos, alpha-MSH restores the corticosteroid-induced growth retardation. Thus alpha-MSH seems to possess general trophic properties. The fetal brain in humans is involved in timing the moment of birth. This process is probably mediated by peptides of the opiomelanocortin family as suggested from observations in anencephaly and other congenital brain anomalies and from the influence of corticosteroids or ACTH on labour. The high percentage of premature deliveries in heroin addicts is worth examining endocrinologically, in this respect. The exact nature of the peptides and mechanisms involved in labour is not yet known. Some peptides of the opiomelanocortin family induce an acceleration of brain development. Neonatal treatment of rats with alpha-MSH alters their later behaviour while ACTH fragments accelerate the onset of eye-opening. Opiates and methadone inhibit brain development, and neonatal administration of beta-endorphin or naloxone causes permanent insensibility to temperature stimuli. The interrelated nature of the fetal pituitary, brain and placenta does not, at present, allow us to pin down which of these structures is primarily involved in the regulation of intrauterine growth, labour and brain development. PMID- 6268379 TI - Pars intermedia peptides: studies in adult humans. AB - A combination of radioimmunoassays and chromatography under acid-dissociating conditions has been used to obtain profiles of ACTH and LPH-related peptides in human plasma and cerebrospinal fluid. The spectra of peptides observed in these two fluids differ markedly. ACTH, beta-LPH, gamma-LPH and beta-endorphin are observed in the plasma of normal subjects and patients with increased pituitary ACTH secretion, whereas cerebrospinal fluid contains ACTH, beta-LPH, gamma-LPH and beta-endorphin, a 31 000-molecular-weight putative precursor having ACTH, LPH and gamma-MSH immunoreactivities, as well as pro-gamma-MSH(1-77) and smaller immunoreactive gamma-MSH fragments, alpha-MSH was not observed in blood or cerebrospinal fluid but this pars intermedia peptide and corticotropin-like intermediate lobe peptide (CLIP) were both found in tumour tissues obtained from patients with the ectopic ACTH syndrome. In vitro studies of human pituitary tumour tissues confirmed concomitant secretion of ACTH, beta-LPH, gamma-LPH, beta endorphin and pro-gamma-MSH, which could be stimulated by a preparation of crude stalk median eminence and synthetic arginine vasopressin, from the rat, and could be suppressed by hydrocortisone. Clinical studies in which electroacupuncture was used to alleviate the symptoms of heroin withdrawal or recurrent pain revealed that concentrations of met-enkephalin and beta-endorphin, respectively, may rise in cerebrospinal fluid in association with relief of symptoms. PMID- 6268380 TI - Biological actions of melanocyte-stimulating hormone. AB - Melanocyte-stimulating hormone (alpha-melanotropin, MSH) may function in a number of diverse physiological roles. MSH stimulates (1) rapid translocation of melanosomes (melanin granules) in dermal melanophores to effect rapid colour change and (2) melanogenesis in normal and abnormal (melanoma) epidermal melanocytes. Both actions involve (1) initial binding of the peptide on the melanocyte membrane, (2) transduction of signal to adenylate cyclase, and (3) increased cytosolic levels of cyclic AMP. Efforts to prepare radioiodinated MSH and analogues for radioreceptor studies using melanoma membranes and intact cells reveal that conventional iodination procedures inactivate the hormone because of oxidative and iodination effects on specific structural components of the peptide. These effects can be circumvented by the use of synthetically tailored MSH analogues. Transduction of signal from receptor to adenylate cyclase requires calcium, but prostaglandin or beta-adrenoceptor stimulation of melanophores does not. The nucleotide and metal ion requirements for mouse melanoma adenylate cyclase activity have been characterized. There is both a transcriptional and translational requirement for MSH stimulation of tyrosinase activity and melanin production in melanoma cells. Melanosome translocation within melanophores is enhanced in the absence of extracellular calcium. A model for the MSH control of melanosome movements suggests a bifunctional, but compartmentalized, role for calcium in the action of MSH. PMID- 6268381 TI - Gamma-melanotropin and brain function. AB - In view of the close structural similarity between the pro-opiocortin fragment, gamma-MSH, and ACTH/MSH-type peptides, the behavioural profile of gamma-MSH was explored. Attention was first focused on behavioural procedures in which ACTH/MSH related neuropeptides have been found effective. It was found that gamma-MSH and ACTH-like neuropeptides had opposite effects on avoidance behaviour. In this respect the activity of gamma-MSH resembles that of opiate antagonists rather than that of beta-endorphin. Accordingly, ACTH(1-24) induced excessive grooming which is blocked by opiate antagonists and is attenuated by gamma-MSH. In addition, gamma-MSH injected into the periaqueductal grey matter of the brainstem of opiate-naive rats elicited symptoms reminiscent of those seen after opiate withdrawal. Gamma-MSH attenuated several effects of intracerebroventricularly administered beta-endorphin (e.g. antinociception, hypothermia, alpha-MSH release) and decreased the acquisition of heroin self-administration. Although gamma-MSH at rather high doses displaced naloxone from its specific binding sites in brain homogenates, it did not interfere with beta-endorphin-induced effects on in vitro muscle preparations (guinea-pig ileum; rat rectum). Interestingly, gamma MSH induced relaxation of the rat rectum in vitro. It is postulated that gamma MSH may attenuate beta-endorphin-induced effects by acting via gamma-MSH receptor sites (functional antagonism), although a pharmacological antagonism cannot be excluded as yet. PMID- 6268382 TI - Comparison of rat anterior and intermediate pituitary in tissue culture: corticotropin (ACTH) and beta-endorphin. AB - The forms of immunoreactive beta-endorphin-sized material in extracts of anterior and intermediate-posterior pituitary from the rat examined by the ion exchange chromatography method of Zakarian & Smyth. The anterior pituitary primarily contained material that co-migrated with synthetic camel beta-endorphin(1-31), whereas the intermediate-posterior pituitary contained relatively little such material. The majority of immunoactive beta-endorphin-sized peptides in the intermediate pituitary eluted at lower concentrations of NaCl than did camel beta endorphin. Conditions were developed for the stable, long-term tissue culture of dissociated intermediate-posterior pituitary cells. Extracts of cells maintained in tissue culture for 18 h or nine days had the same content of immunoreactive beta-endorphin, 16k fragment, ACTH(18-39) (or CLIP) and ACTH(17-24). Throughout the nine days in culture, characteristic cells that could be immunostained with antibodies to various regions of pro-ACTH/endorphin were present; during the time in culture, non-reactive background cells multiplied rapidly. The major proteolytic processing of pro-ACTH/endorphin remained characteristic of intermediate pituitary tissue throughout the nine days in tissue culture, and did not become similar to the simpler pattern of proteolytic processing found in the anterior pituitary. PMID- 6268383 TI - Processing, turnover and release of corticotropins, endorphins and melanotropin in the toad pituitary intermediate lobe. AB - The significance of glycosylation of the ACTH/alpha-MSH-endorphin precursor in the biosynthesis, processing and secretion of its peptide products was examined in the toad neurointermediate (intermediate - posterior) lobe, with the aid of a specific inhibitor of glycosylation, tunicamycin. Tunicamycin did not affect the synthesis of the precursor but prevented its glycosylation. In the presence of tunicamycin the precursor underwent rapid intracellular degradation. Precursor molecules that escaped complete degradation were processed to an ACTH molecule with approximately 19 000 molecular weight and to other atypical peptides, which were released. In vitro studies showed that trypsinization of the non glycosylated precursor resulted in its random proteolysis while large forms of ACTH were cleaved from the glycosylated precursor. The results indicate that glycosylation of the ACTH/alpha-MSH-endorphin precursor may confer specific conformational properties upon the molecule, thus regulating its limited proteolysis. Turnover and release studies revealed two different pools of ACTH, beta-LPH and alpha-MSH-related peptides in the toad intermediate lobe. One pool contained ACTH, beta-LPH, alpha-MSH and beta-endorphin, which were rapidly synthesized and released, or degraded within 6 h of synthesis if their release was inhibited. The other pool was stored and was stable for at least 10 h, if prevented from being released. Peptides in this stored pool primarily included ACTH, alpha-MSH and beta-LPH; beta-endorphin was a minor component of this pool. The release from both pools of peptides was inhibited by dopamine, while the stored pool was selectively inhibited from release by L-isoprenaline (L isoproterenol). PMID- 6268384 TI - Beta-endorphin-related peptides in the pituitary gland: isolation, identification and distribution. AB - A new procedure is described for isolation of four forms of beta-endorphin from bovine pituitary. The four peptides are: the C-fragment of lipotropin (bovine lipotropin residues 63-93, or beta-endorphin, the alpha, N-acetyl derivative of the C-fragment, the C'-fragment (bovine lipotropin residues 63-89) and the alpha, N-acetyl derivative of the C'-fragment. Of these peptides, beta-endorphin alone possesses potent analgesic activity. The procedure has been applied in studying the distribution of beta-endorphin-related peptides in two regions of the pituitary. The results show that in the anterior pituitary of the pig and the rat, beta-endorphin is produced with a high degree of specificity in its opiate active form. In contrast, in the pars intermedia of both species at least six peptides related to beta-endorphin are elaborated and beta-endorphin represents only a minor component. The principal peptides in the pars intermedia have been identified as acetylated derivatives of lipotropin C'-fragment: in the pig the predominant peptide is alpha,N-acetyl C'-fragment and in the rat the major peptide appears to be an epsilon-acetylated derivative of alpha,N-acetyl C' fragment. Thus, beta-endorphin is activated in the anterior pituitary and inactivated in the pars intermediate. The results demonstrate selective and specific processing of the 31K ACTH-endorphin prohormone in the different regions of the pituitary. In the anterior pituitary two biologically active peptides, ACTH and beta-endorphin, are generated together; in the pars intermedia alpha melanotropin (alpha-MSH) is accompanied by forms of beta-endorphin that have been inactivated by acetylation and proteolysis. PMID- 6268385 TI - Intracytoplasmic immunofluorescence in multiple myeloma. AB - A new intracytoplasmic immunofluorescence staining procedure has been investigated to detect and quantify myeloma cells by means of flow cytometry. Freshly harvested bone marrow aspirations from 12 patients with multiple myeloma were treated with collagenase and Triton X-100, and incubated with different specimens of fluoro-isothiocyanate-marked antihuman immunoglobulins. DNA-staining was then done with propidium iodide. Biparametric evaluation in a cytofluorograph 6300A/FC 200 showed a characteristic cluster distribution of normal and pathological immunoglobulin-producing cells. This intracytoplasmic fluorochromic staining procedure may be significant for the specific identification of nonsecretive immunocytomas, which cannot be detected by serodiagnostic methods. PMID- 6268386 TI - SV40-infected muntjac cells: cell cycle kinetics, cell ploidy and T antigen concentration. AB - Muntjac cells in which the SV40 virus neither readily causes transformation nor replicates were used to study the effect of SV40 infection on cell ploidy and the influence of ploidy on the concentration of T antigen, which is required for the initiation of viral DNA synthesis. Both the DNA content, as measured by the flow microfluorometry of propidium iodide-DNA fluorescence, and the average number of chromosomes per cell indicated that infection with SV40 did not alter the ploidy of the host cell. SV40 infection had no effect on the ploidy distribution of muntjac cells. After immunofluorescence staining with anti-T serum and fluorescein-labeled anti-gamma G, infected and uninfected cultures were compared. In uninfected cells incubated with a 1:20 dilution of anti-T serum no fluorescence could be observed by fluorescence microscopy, but when examined by flow microfluorometry, fluorescence was detected after staining with as little as 1000-fold diluted antiserum. Determination of the amount of T antigen and DNA content in the same cell by simultaneous measurement of fluorescein isothiocyanate-conjugate and propidium iodide fluorescence, indicated that the cellular concentration of T antigen did not vary with the ploidy of the genome or the number of nuclei per cell. These results suggest that gene dosage is not a factor which determines the permissive environment for SV40 replication. PMID- 6268387 TI - High fiber diet benefits for diabetics. PMID- 6268388 TI - Diagnosis and treatment of five parasites. Enterobius vermicularis, Giardia lamblia, Trichuris trichiura, Ascaris lumbricoides, Entamoeba histolytica. AB - General descriptions and monographs of the five parasites most likely to be seen in U. S. patients are presented. The appended monographs are designed to be a starting reference for answering drug information questions regarding these parasites. The drugs covered in the monographs are listed in the order of suggested use. PMID- 6268389 TI - [Is surgical treatment of small cell bronchial carcinoma still indicated?]. AB - Based on own results, general negation of operation in small cell carcinoma of the lung does not appear warranted. Surgical treatment is indicated when a non metastasizing tumour is present. Small cell bronchial carcinoma operated in tumour stage I has a clearly better prognosis than a carcinoma of the same stage treated by chemo- or radiotherapy. A certain response of these carcinomas to cytostatic or radiotherapy has not been established. Should tumour metastases be demonstrable, i.e. lymph node metastases in the mediastinum or distant metastases, as is the case in the majority of these rapidly metastasizing carcinomas, chemo- or radiotherapy has been shown to be superior to operative treatment. PMID- 6268390 TI - [Manifestation of an acquired cytomegalovirus infection as encephalitis in childhood]. PMID- 6268391 TI - [Subacute cerebellar degeneration]. PMID- 6268392 TI - Interaction of thyroid hormones and cortisol on binding proteins of cytosol and nuclear extract of human leukocytes. AB - Competitive properties of thyroid hormone analogues and cortisol for the binding of triiodothyronine and thyroxine, expressed as apparent inhibition constants (Ki), have been measured in nuclear extract and cytosol proteins of human leukocytes by means of electrophoresis in polyacrylamide gradient gel and charcoal-dextran assay. In the cytosol not only thyroid hormones but also cortisol competed for the binding of triiodothyronine and thyroxine as tested by charcoal-dextran assay. By means of electrophoresis two protein fractions binding thyroid hormones were found: protein fraction designed A (m. w. 100,000) and protein fraction B (m. w. 83,000). In protein fraction A the inhibition constant Ki for thyroid hormones are lower than in protein fraction B. In the protein fraction B not only thyroid hormones but also cortisol competed for the binding of triiodothyronine and thyroxine. In the nuclear extract the thyroid hormones were bound in one protein fraction C (m. w. 58,000) only. In this protein fraction only thyroid hormones, but not cortisol, are competitors for the binding of triiodothyronine and thyroxine and in the following descending order: triiodothyronine, thyroxine, tetraiodothyroacetic acid, thyroxamine and D thyroxine. The competition of cortisol for the binding of thyroid hormones in cytosol protein fraction B in connection with some serum TBG changes in patients after prednisone administration is discussed. PMID- 6268393 TI - Reversal of diabetes by isogeneic transplantation of cultured pancreatic islets. AB - Pancreatic islets were isolated by collagenase digestion from female Wistar rats and cultured at 20 mmol/l glucose. The enhancement of Mg++ concentration from 0.8 mmol/l up to 5.3 mmol/l had a protecting effect on the glucose-induced insulin release in the subsequent short-time incubation and prevented the age-depending decrease of B-cell function. About 1,000 cultured islets injected into portal vein normalized the plasma glucose of streptozotocin-diabetic rats. The plasma glucose patterns during the glucose load were nearly identical to healthy controls. These findings suggest that the cultured islets maintain the ability to secrete insulin in response to glucose in vitro as well as in vitro and that such islets can reverse an experimentally induced diabetes. PMID- 6268394 TI - Parathyroid hormone, cAMP, electrolytes and uric acid after high dose CaCl2 in patients with idiopathic stone formation. AB - High dose levels of calcium chloride significantly decrease serum level of parathyroid hormone (PTH) in both patients with history of idiopathic stone formation and healthy controls. Suppressibility of parathyroid glands is obtained by injection of 10 ml 10% calcium chloride without any restriction in calcium diet. Serum levels of calcium measured 14 mg/dl 10 min. after high dose calcium chloride injection and distinctly affect cAMP in urine in patients when compared to healthy controls. The elimination of electrolytes and uric acid is elevated 40 min. after calcium application in both patients and controls and returns to normal values 120 min. later. No stone formation has been observed in an eighteen mouth follow up of all subjects studied. PMID- 6268395 TI - Effect of dibutyryl cyclic adenosine 3'5'-monophosphate on the adrenal cortex mitotic activity in hypophysectomized rats. PMID- 6268396 TI - Insulin receptor: structure and function. PMID- 6268397 TI - Lipoprotein utilization and cholesterol synthesis by the human fetal adrenal gland. AB - A model proposed for regulation of steroidogenesis, lipoprotein utilization and cholesterol metabolism in HFA tissue is presented in Fig 17. We envision that the role of ACTH and cAMP in steroidogenesis and cholesterol metabolism is as follows. ACTH binds to specific receptors on the surface of the cells of the HFA gland and as a consequence, adenylate cyclase is activated, leading to increased formation of cAMP. cAMP causes activation of protein kinase that leads, presumably, to phosphorylation of specific proteins. This leads to the initiation of reactions that give rise to increased activity of key enzymes and levels of proteins involved in adrenal cholesterol metabolism. Presumably, the action of ACTH causes an increase in the activity of cholesterol side chain cleavage, the rate-limiting step in the conversion of cholesterol to steroid hormones. We suggest that once the mitochondrial cholesterol side-chain cleavage system is fully activated by ACTH, the supply of cholesterol to the mitochondria becomes rate-limiting for steroidogenesis. To meet this demand for cholesterol, a further action of ACTH results in an increase in the number of LDL receptors. LDL binds to specific receptors on the cell surface that are localized in coated pits. LDL is internalized by a process of adsorptive endocytosis and the internalized vesicles fuse with lysosomes and the protein component of LDL is hydrolyzed by lysosomal proteolytic enzymes to amino acids. The cholesteryl esters of LDL also are hydrolyzed to give rise to fatty acids and cholesterol. The liberated cholesterol is available for utilization in the biosynthesis of steroid hormones and other cellular processes. In addition, ACTH stimulates the activity of HMG CoA reductase and, thus, the rate of de novo cholesterol biosynthesis. In this way sufficient cholesterol is obtained to provide for precursor cholesterol to maintain the high rate of steroid synthesis by the HFA. HDL is not utilized as a source of cholesterol by the HFA. Because of the rapid rate of utilization of LDL by the HFA, fetal plasma levels of LDL are low and the activity of the HFA is a primary determinant of these levels. Thus, in the case of anencephaly, in which the activity of the adrenal is very low, plasma levels of LDL are 2--3 times higher than in normal fetuses, whereas plasma HDL levels are similar. In addition, in the normal neonate plasma LDL levels rise rapidly after birth, and this event is coincident with the involution of the fetal zone of the adrenal. The fetal liver is likely to be the major source ultimately of the LDL cholesterol utilized by the HFA. Consequently, factors that regulate cholesterol and lipoprotein synthesis in the fetal liver may, in turn, affect the steroidogenic activity of the HFA through regulation of the supply of cholesterol precursor. Thus, if trophic factors for the HFA other than ACTH exist, an important site of their action might be the fetal liver, rather than a direct action to influence the rate of synthesis of steroids by the fetal adrenal. PMID- 6268398 TI - Melatonin.l A mammalian pineal hormone. PMID- 6268399 TI - The glucagonoma syndrome: clinical features, diagnosis, and treatment. PMID- 6268400 TI - Factors which affect superoxide anion release from rat alveolar macrophages. AB - In order to investigate some of the characteristics of superoxide anion release from alveolar macrophages, the effects of substances known to influence superoxide release from polymorphonuclear leukocytes (PMN) were studied in rat alveolar macrophages. There is a relatively small, but constant, amount of superoxide released from alveolar macrophages at rest. The amount released increases 5- to 6-fold and becomes maximal in about 20-30 min following exposure to unopsonized zymosan particles. The rate of superoxide release is maximal only 2 min after exposure of the cells to particles, i.e., long before particle uptake is complete. In addition to particles, release of superoxide anion can be stimulated by phorbol-12-myristate-13-acetate (PMA). Lectins and chemotactic factors, which stimulate release in PMN, have little or no effect in alveolar macrophages. Superoxide release during exposure to zymosan appears to be dependent upon extracellular Ca++. Also, the release mechanism can be affected by the addition of cyclic AMP or various protein modifiers to the medium. Since many of these findings differ from those reported by others for PMN, the control of superoxide anion release from alveolar macrophages and PMN is probably different. PMID- 6268401 TI - The cotton rat as an experimental model of human parainfluenza virus type 3 disease. AB - Intranasal or aerosol inoculation of cotton rats (Sigmodon hispidus) with human parainfluenza virus type 3 (P3) produces pulmonary changes which closely resemble human disease due to this agent. Active viral replication resulted in peak titers by day 2 of infection. Viral antigen was localized by immunofluorescence in bronchial epithelial cells alone (aerosol inoculation) or epithelial and alveolar cells (intranasal instillation). Cytopathic effects in epithelial cells was noted as early as day 2, and marked cellular proliferation occurred by day 7. Intranasal instillation of virus resulted in development of patchy interstitial pneumonitis. Mononuclear cell infiltration in the peribronchial and perivascular areas peaked on days 6 and 7. A brisk systemic antibody response was measured both by complement fixation and virus neutralization techniques. These data establish the value of the cotton rat as an experimental model for the study of bronchiolitis and pneumonia due to P3. Since previous work has demonstrated that respiratory syncytial virus and Mycoplasma pneumoniae also will replicate and cause pulmonary disease in cotton rats, comparative studies in a single animal species are facilitated. PMID- 6268402 TI - Cytotoxic and mutagenic properties of shale oil byproducts. I. Activation of retort process waters with near ultraviolet light. AB - Cultured Chinese hamster ovary (CHO) cells were exposed to dilutions of shale oil retort process waters obtained from three different retorting processes located in the Green River oil shale formations in the western part of the United States. Although the intensity of the response was dictated by thd process water used, all induced a cytotoxic (reduction in colony-forming ability) and mutagenic (induced at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus) response in cells pretreated with dilutions of the waters and subsequent exposure to near ultraviolet light (NUV). Combinations of process water plus NUV yielded mutation frequencies as great as 50% that witnessed for the mutation frequency induced by the potent carcinogen far ultraviolet light. NUV alone was nontoxic and nonmutagenic at the doses of radiation used. Exposure of CHO cells in the dark to nontoxic dilutions of the process waters resulted in small but significant increases in 6-thioguanine resistant mutants. (1-2 time background rates). The biological consequences resulting from the disposal of retort process waters into the delicate environment present in this oil shale region could be further complicated by this photoactivating process. PMID- 6268403 TI - Decomposition of organolead compounds in aqueous systems. PMID- 6268404 TI - Studies on the mechanism of pyrophosphate-mediated uptake of iron from transferrin by isolated rat-liver mitochondria. AB - 1. Respiring rat liver mitochondria accumulate iron released from transferrin by pyrophosphate. The amount of iron accumulated is 1--1.5 nmol mg protein-1 h-1, or approximately 60% of the amount of iron mobilized from transferrin. 2. The uptake declines if respiration is inhibited, substrate is deleted, or the experiments are run under anaerobic conditions. Substrate depletion and respiratory inhibitors are less inhibitory under anaerobic conditions. 3. More than 80% of the amount of iron accumulated by aerobic, actively respiring mitochondria can be chelated by bathophenanthroline sulphonate, and with deuteroporphyrin included, up to 30% of the amount of iron accumulated is recovered as deuteroheme. Iron accumulated by respiration-inhibited mitochondria under aerobic conditions is not available for heme synthesis. 4. With time the uptake of iron increases eightfold relative to the uptake of pyrophosphate. 5. The results are compatible with a model in which ferric iron is mobilized from transferrin by pyrophosphate, ferric iron pyrophosphate is bound to the mitochondria, iron is reduced, dissociates from pyrophosphate and is taken up by the mitochondria. Ferrous iron thus formed is available for heme synthesis. PMID- 6268405 TI - Nuclease-sensitive regions on the extrachromosomal r-chromatin from Tetrahymena pyriformis. AB - The extrachromosomal DNA coding for the ribosomal precursor in Tetrahymena contains a transcribed region with a size of 6 x 10(3) base pairs plus non transcribed central and distal spacers. In the present study the chromatin structure of the transcribed region and the terminal spacer have been compared. Micrococcal nuclease and DNase I were used to investigate the nucleosomal and the higher order structures. The specific DNA fragments were visualized by gel electrophoresis, Southern blotting onto nitrocellulose sheets and hybridization with specific 32P-labelled RNA probes. Investigations of the cleavage patterns demonstrate the presence of a defined nucleosomal structure in the non transcribed region, while there is no indication of a nucleosomal pattern in the transcribed region. Specific regions on the r-chromatin are hypersensitive to DNase I. The first cleavage occurs in the non-transcribed central spacer region, while the second cleavage takes place in a region near the 3' end. The hypersensitivity of the central part of r-chromatin is also found by autodigestion in isolated nucleoli. PMID- 6268406 TI - Binding of spermine to tRNATyr stabilizes the conformation of the anticodon loop and creates strong binding sites for divalent cations. AB - Electron spin resonance (ESR) spectra of yeast tRNATyr. spin-labelled in the isopentenyladenosine residue adjacent to the anticodon, were measured as a function of temperature at various spermine/tRNA ratios. The critical temperature, at which a change in the activation energy for spin-label motion takes place, changes abruptly by almost 10 degrees C upon the addition of the fifth spermine molecule/tRNATyr molecule, indicating a marked stabilization of the anticodon region. Scatchard plots for Mn2+ binding to tRNATyr in the presence of spermine do not follow theoretically predicted curves for electrostatic type of interaction, assuming that four negative charges on tRNA are neutralized by each spermine molecule. It was estimated that two to three new binding sites for divalent cations are created upon the binding of spermine to tRNATyr. PMID- 6268407 TI - Modification of the spectral properties of cytochrome b in mutants of Saccharomyces cerevisiae resistant to 3-(3,4-dichlorophenyl)-1,1-dimethylurea. Mapping at two distinct genetic loci of the split mitochondrial gene of cytochrome b. AB - The effects of five inhibitors of the cytochrome bc1 complex: 3-(3,4 dichlorophenyl)-1,1-dimethylurea (diuron), 2-n-heptyl-4-hydroxyquinoline-N-oxide (HpHOQnO), antimycin A, funiculosin and mucidin were measured in submitochondrial particles of strains of the yeast Saccharomyces cerevisiae belonging to two classes of diuron-resistant mutants Diu 1 and Diu 2 which are modified in different exons of the split mitochondrial gene of cytochrome b. 1. The oxidation of NADH and of cytochrome b-561 exhibits a similar resistance to diuron and HpHOQnO in Diu 1 and Diu 2 mutants. 2. No extra reduction of cytochrome b-561 and cytochrome b-565 is observed in the presence of diuron and HpHOQnO. 3. Both Diu 1 and Diu 2 mutants exhibit the red shift of cytochrome b-561 induced by concentrations of HpHOQno 2 -- 3-times higher than those required in the parental strains. 4. The spectral and respiratory effects of antimycin A, funiculosin and mucidin and generally similar in the diuron-resistant mutants and in their parental strains. However a cross-resistance between diuron and antimycin A is indicated in one Diu 2 mutant. 5. From the combined genetic and biochemical data it is concluded that the interaction of diuron and HpHOQnO with cytochrome b is mediated by at least two specific amino acids located apart in the central region of the apocytochrome b peptide coded by mitochondrial DNA. These two amino acids control tightly the extra reduction of cytochromes b-565 and b-561 as well as the flow of electrons through the bc1 complex. However the binding of HpHOQnO required for the expression of the red shift of cytochrome b-561 is only slightly affected by the diu-1 and diu-2 mutations. PMID- 6268408 TI - ATP prevents both hydroperoxide-induced hydrolysis of pyridine nucleotides and release of calcium in rat liver mitochondria. AB - The mechanism of the hydroperoxide-induced release of calcium from rat liver mitochondria was investigated. In calcium-loaded mitochondria both the hydroperoxide-induced hydrolysis of pyridine nucleotides and the release of calcium is inhibited by intramitochondrial ATP. In submitochondrial particles, in the absence of ATP a hydrolytic product of NAD+, probably ADP-ribose, binds covalently to a protein of the inner mitochondrial membrane. It is proposed that a compound deriving from NAD(P)+ is an important factor in the calcium release mechanism in rat liver mitochondria. PMID- 6268409 TI - Inhibitory effect of prostaglandins on the stimulation by glucagon and adrenaline of formation of cyclic AMP in rat hepatocytes. AB - Several prostaglandins were found to inhibit hormone-induced cyclic AMP accumulation in suspensions of intact rat hepatocytes. Prostaglandin E1 in concentrations of 0.05--25 micrometers inhibited the cyclic AMP response to glucagon. Maximal inhibition was about 50%. The effect was rapid, being evident within 30 s. Prostaglandins E2, F1 alpha, F2 alpha, A1 and A2 also inhibited the glucagon effect on cyclic AMP in hepatocytes. In cells made highly responsive to adrenaline, by pretreatment of the animals with the carcinogen 2 acetylaminofluorene, and inhibitory effect of prostaglandin E1 was seen also on adrenaline-induced cyclic AMP accumulation. The mechanism of the inhibitory effect of prostaglandins on hormone-stimulated cyclic AMP accumulation was not clarified. Prostaglandin E1 did not inhibit glucagon binding to intact hepatocytes, and so far we have not been able to demonstrate any effect of the prostaglandins on the adenylate cyclase or phosphodiesterase in broken cell preparations. It is concluded that while several previous studies have shown that stimulatory effects of prostaglandins on cyclic AMP are only marginal or lacking in parenchymal liver cells the present data indicate that several prostaglandins exert strong inhibitory interference with hormone-induced cyclic AMP accumulation. PMID- 6268410 TI - Purification and properties of the restriction endonuclease BglII from Bacillus globigii. AB - The restriction endonuclease BglII from Bacillus globigii has been purified to homogeneity. The enzyme is a dimer of two subunits of Mr = 27000. The reaction mechanism does not involve the accumulation of a DNA intermediate nicked in one strand and the enzyme is not affected by superhelical twists in the substrate DNA, indicating that DNA binding does not involve either winding or unwinding of the double helix. Antibodies were prepared against BglII. These antibodies did not cross react with any other restriction endonucleases tested, including other enzymes from B. globigii or from closely related strains. It is thus unlikely that type II restriction enzymes represent a closely related group of proteins. PMID- 6268411 TI - Citrate-dependent iron transport system in Escherichia coli K-12. AB - Induction of the citrate-dependent iron transport system of Escherichia coli K-12 required 0.1 mM citrate and 0.1 micrometer iron in the growth medium. Five--ten times more iron than citrate was taken up into the cells which suggests that citrate was largely excluded from the transport. Fluorocitrate and phosphocitrate induced the citrate-dependent iron transport system although they supported iron uptake only very poorly. An outer membrane protein (FecA), belonging to the transport system, was induced in fecB mutants which were devoid of citrate dependent iron transport. The intracellular citrate and iron concentrations were 10--100-times higher than the external concentrations required for induction of the transport system. It is concluded that only exogenous ferric citrate induced the transport system, and that citrate did not have to enter the cytoplasm. The Tn10 transposon, conferring tetracycline resistance, was inserted near the fec gene region which controls the expression of the citrate-dependent iron transport system. The determination of the cotransduction frequencies of Tn10 with the fecA and fecB markers suggested the gene order fecA fecB Tn10. PMID- 6268412 TI - Production of Curie quantities of high purity I-123 with 15 MeV protons. AB - Using the technology described for electrodeposition of elemental tellurium, it is possible to bombard a target with 2 kW of proton beam power without significant loss of radio iodine. If Te-123 enriched to 96% is used as target material, the I-123 yield would be about 1 Curie with a 0.23% I-124 impurity for a 2-h bomardment with 130 muA of 15 MeV protons. The same I-124 impurity level can be maintained with a lower enrichment of Te-123 by reducing the proton energy to 11.5 meV, but with a consequent reduction in I-123 yield. PMID- 6268413 TI - Accumulation of 99mTc-pyrophosphate in a muscle hernia of the thigh. PMID- 6268414 TI - Effects of guar on plasma viscosity and related parameters in diabetic children. AB - Ten diabetic children supplemented their normal diets with 0.45 g/kg/day guar gum for 4 weeks. They experienced a decrease in (1) plasma fibrinogen, (2) insulin requirement, (3) serum osmolality and (4) plasma viscosity; and an increase in serum albumin and total serum protein concentrations. The decrease in plasma viscosity, which was statistically significant, depended on the increase of albumin and the decrease of fibrinogen and may have some significance to the development of diabetic microangiopathy. The sequence of events eventually leading to a decrease of plasma viscosity is possibly mediated by gip and glucagon, consecutively. PMID- 6268415 TI - Effect of diethyldithiocarbamate on the metabolic elimination of hexobarbital, phenazone, tolbutamide and four halogenated hydrocarbons. AB - The present study describes the inhibitory effects of diethyldithiocarbamate (dithiocarb) on the metabolic elimination of hexobarbital, phenazone, tolbutamide and four halogenated hydrocarbons. The plasma half-life for the beta-slopes of hexobarbital (25 mg/kg, i.v.) and phenazone (50 mg/kg, i.v.) were increased 2.5 and 3.5 fold respectively, when dithiocarb (100 mg/kg, i.p.) was administered simultaneously. The plasma half-life of tolbutamide was 2.27 h, when administered alone to rats; and 4.04 h, when administered with dithiocarb. Metabolic elimination of halothane, trichloroethylene, dichloroethane, and carbon tetrachloride, from the atmosphere of a closed exposure system was studied in rats. Treatment with dithiocarb (100 mg/kg, i.p.) immediately before exposure, prolonged the elimination half-life of: halothane (103 parts/10(6)) by a factor of 7.6, of trichloroethylene (25 parts/10(6)) by a factor of 5.3; dichloroethane (69 parts/10(6)) by 4.6; and carbon tetrachloride (38 parts/10(6)) by 2.4, respectively. The inhibitory actions of dithiocarb on the metabolism of the tested drugs and chemicals are explained as the consequences of a depressed microsomal mono-oxygenase activity due to a decrease in the cytochrome P 450 content. PMID- 6268416 TI - Presynaptic effects of bekanamycin at the frog neuromuscular junction. Reversibility by calcium and aminopyridines. AB - The effects of bekanamycin (5-320 microM) on evoked and spontaneous transmitter release were examined in frog neuromuscular junctions in vitro by using conventional electrophysiological techniques. Bekanamycin in a concentration dependent fashion reduced reversibly the quantal content of the end-plate potentials while it had no observable effect on the configuration of the extracellularly recorded presynaptic action potential. The reduction in evoked transmitter release produced by bekanamycin could be antagonized either by increasing the external calcium concentration or by drugs like the aminopyridines which are to greatly enhance transmitter release from motor nerve terminals. Regarding the possible mode of action of bekanamycin on transmitter release our results are consistent with the hypothesis that there is competition between calcium and bekanamycin in the excitation-secretion coupling process and that the site of competition has a higher affinity for bekanamycin than for calcium. Bekanamycin also reduced in a dose-dependent manner the acceleration of miniature end-plate potentials induced by increasing the extracellular K+ concentration while it had no effect on spontaneous miniature end-plate potential frequency in resting junctions. Besides its inhibitory pre-junctional effects bekanamycin in concentrations higher than 40 microM decreased dose-dependently the amplitude of miniature end-plate potentials. However, presynaptic effect predominated and seemed to be quantitatively more important for the neuromuscular block than was a possible postsynaptic action of the antibiotic. It is concluded that bekanamycin exerts potent inhibitory effects on transmitter release probably by interfering with the influx of calcium that occurs during depolarization of motor nerve terminals. PMID- 6268417 TI - Correlation between pharmacological and opiate receptor binding activities of tetrapeptide acylhydrazide analogs of enkephalin. AB - The pharmacological and opiate receptor binding activities of four synthetic tetrapeptide acylhydrazide analogs of enkephalin (EK compound) were compared with those of reference compounds. EK-159 administered subcutaneously was less analgesic, while EK-209, EK-259 and EK-272 were more potent than morphine in the hot plate, Haffner's and phenylquinone writhing tests in mice. EK-272 being the most active was comparable to what was found with FK-33824. IC50 values of EK compounds in a sodium-free medium in the opiate receptor binding assay were lower than the values seen with morphine. The binding activities of EK compounds in 100 mM NaCl medium showed a clearer correlation with their analgesic activities than was seen in the absence of sodium ion. The binding affinity of EK-272 was the highest and the sodium response ratio (IC50 + NaCl/IC50-NaCl) was slightly lower than that of pentazocine. The analgesic action in rodents, respiratory inhibition in rabbits, inhibition of intestinal movement in mice, and hyperthermic action in rats, were all qualitatively, but not quantitatively similar to the effects seen with morphine. The analgesic action of EK compounds was relatively resistant to the antagonizing effect of naloxone and the EK compounds modified the analgesic action of morphine. These properties were inversely correlated with the sodium response ratios. PMID- 6268418 TI - Receptor binding and antinociceptive properties of phencyclidine opiate-like derivatives. AB - The relative potencies of a new series of phencyclidine (PCP) analogs for the displacement of [3H] morphine binding from rat brain homogenates are well correlated with the relative antinociceptive potencies in the test of writhing induced by acetic acid (0.6%). One group of compounds exerts a completely naloxone-reversible analgesic effect, while the effects of a second group are partially reversed by naxolone. These findings and the structural differences between the two groups suggest that their analgesic is mediated through different opiate receptors. PMID- 6268419 TI - Effect of chronic morphine treatment on beta-endorphin biosynthesis by the rat neurointermediate lobe. AB - The effect of chronic morphine treatment on the in vitro biosynthesis of beta endorphin by rat pars intermedia was investigated. Tolerance and physical dependence were induced in 200 g rats by the subcutaneous implantation of 75 mg morphine pellets for either 3 days or 15 days. Immediately following sacrifice of the animals the neurointermediate lobes were removed and incubated with [3H] phenylalanine. The protein extracts of the lobes were analyzed for the incorporation of the labelled amino acid into total protein, pro opiomelanocortin, beta-lipotropin (beta-LPH) and beta-endorphin. the biosynthesized products were purified by immunoprecipitation with an antiserum to beta-endorphin. The identity and purity of beta-endorphin were verified by polyacrylamide disc gel electrophoresis with sodium dodecyl sulfate, and microsequencing. The identity of pro-opiomelanocortin (POMC) was verified by peptide mapping of its tryptic digestion products. The results showed that morphine treatment induced a decrease in the incorporation of the radioactive amino acid into total protein, pro-opiomelanocortin, beta-LPH and beta-endorphin. The decrease was more pronounced for the incorporation into beta-LPH and beta endorphin than into pro-opiomelanocortin and total proteins, suggesting an effect of morphine treatment on the processing of the pro-opiomelanocortin to its final maturation products. PMID- 6268420 TI - Sympathetic nerve terminal destruction has no effect on specific [3H]ouabain binding to intact mouse and rat skeletal muscle. AB - Following pretreatment with 6-OH-dopamine, the sympathetic nerve endings of the iris and skeletal muscle of mice and rats were not longer detectable by cytochemistry for noradrenaline. In the same animals, the specific binding of [3H] ouabain to intact soleus muscles was not significantly different from that measured in controls, Neither ouabain-suppressible 42K uptake nor Na-K contents were affected by chemical sympathectomy. PMID- 6268421 TI - Effect of chronic lithium treatment on isolation-induced behavioral and biochemical effects in mice. AB - The following effects were induced in mice by a prolonged of isolation (6-7 weeks from weaning): (1) reduction in motor activity; (2) reduction in the effect of oxotremorine on rectal temperature; (3) increase in the response to salbutamol, a beta-adrenergic stimulant. Chronic lithium treatment (2 mg/ml in the drinking water during the last 3-4 weeks of isolation) prevented these phenomena. The number and affinity of beta-adrenergic receptors in the whole mouse brain (excluding the cerebellum) was unmodified by either isolation or by lithium. It is suggested that lithium blocks isolation-induced hypersensitivity, especially of the beta-adrenergic system; this mechanism may be involved in the therapeutic action of lithium. PMID- 6268422 TI - Acetylmethadol metabolites influence opiate receptors and adenylate cyclase in amygdala. AB - The activity of acetylmethadol and two major metabolites of this drug, noracetylmethadol and dinoracetyl-methadol were studied in monkey brain amygdaloid tissue. This tissue contains opiate receptors which may be assessed by direct binding studies; also these receptors are coupled to and capable of modulating a dopamine-stimulated adenylate cyclase system. Etrophine and D-ALa2 Met-enkephalin exhibited similar potencies when assessed for inhibition of dopamine-stimulated adenylate cyclase or competition for [3H] D-Ala2-Met enkephalin binding sites. While acetylmethadol displaced [3H] D-Ala2-Met enkephalin binding sites with a Ki of 7.4 X 10(-7) M, it had no detectable activity in the opiate receptor coupled adenylate cyclase system. Noracetylmethadol and dinoracetylmethodol, however, were capable of both binding (Ki values, 5.6 and 1140 nM respectively) as well as inhibiting the dopamine stimulated adenylate cyclase system (IC50 values, 1.2 and 800 nM respectively). Thus, it appears that metabolism of acetylmethadol to its mono-demethylated form results in a compound more active in both assay systems. The further demethylation of noracetylmethadol results in a second, but less potent, active metabolite. This process of biological activation can be assumed to account for the slow onset and long duration of action of acetylmethadol. PMID- 6268423 TI - Binding of beta-carboline-3-carboxylic acid ethyl ester to mouse brain benzodiazepine receptors in vivo. AB - beta-Carboline-3-carboxylic acid ethyl ester (beta-CEE) displaced [3H] flunitrazepam from the mouse brain benzodiazepine receptor in vivo with an i.v. ED50 of 2.1 mg/kg, an i.p. ED50 and 53.4 mg/kg, and an i.g. ED50 of 450 mg/kg. At 2.1 mg/kg i.v. beta-CEE displaced 37 +/- 9% of the label from hippocampal membranes and 76 +/- 7% from cerebellar membranes. The results suggest that the in vitro binding specificity of beta-CEE is also expressed in vivo and that the drug may act in vivo by binding to the benzodiazepine receptor. PMID- 6268424 TI - Lipid-induced modulation of opiate receptors in mouse brain membranes. AB - The binding of [3H] D-Ala-enkephalinamide (DAEA) to crude mitochondrial fractions (P2M) from mouse forebrain was determined after modulation of membrane lipid microviscosity. Lipid fluidization of P2M membranes, following treatment with egg lecithin, resulted in a 50% loss of specific binding of DAEA. Increasing the P2M lipid microviscosity, by incorporation of cholesteryl hemisuccinate (CHS), increased the accessibility of the opiate receptors up to a peak level of 170% which decreased sharply upon further increase in lipid microviscosity. The processes resulting from lipid rigidification may have important implications for aging and for drug addiction. PMID- 6268425 TI - Allosteric modulation by leucine-enkephalin of [3H]naloxone binding in rat brain. AB - The interaction of morphine and leucine-enkephalin with the binding site labeled by [3H]naloxone in the presence of sodium was compared. The effect of fixed concentrations of morphine and leucine enkephalin on the saturation binding of [3H]naloxone demonstrated that whereas morphine was a competitive inhibitor, leucine enkephalin caused a dose-dependent masking of binding sites. From these data we conclude that the enkephalin receptor is allosterically coupled to the morphine receptor. PMID- 6268426 TI - Centrally mediated pressor response to metiamide as a result of GABA-receptor antagonism. AB - The mechanism of the pressor response to metiamide was examined in anesthetized cats. Intravenous administration of metiamide had no effect on blood pressure. Infusion into the lateral ventricle (10 mg/kg/min for 10 min), caused a marked pressor response which was due to an increase in sympathetic outflow since pretreatment of cats with guanethidine completely prevented it. In a rat brain synaptosome preparation, both metiamide and cimetidine displaced [3H] CABA. These data strongly suggest that metiamide increases blood pressure in the cat through a central mechanism involving GABA-receptor antagonism. PMID- 6268428 TI - Quinolinic acid: a potent endogenous excitant at amino acid receptors in CNS. PMID- 6268427 TI - Alpha 1-adrenoceptor activation stimulates ureogenesis in rat hepatocytes. AB - Epinephrine produced a dose-dependent stimulation of ureogenesis. Epinephrine action was unaffected by the beta-adrenergic antagonist propranolol but was blocked by the alpha-adrenergic antagonists prazosin and yohimbine. Prazosin was approximately 3 orders of magnitude more potent than yohimbine, indicating that the adrenoceptor involved in this action is of the alpha 1-subtype. PMID- 6268429 TI - [3H] Ethyl beta-carboline-3-carboxylate binding to the benzodiazepine receptor is not affected by GABA. PMID- 6268430 TI - Quantitative autoradiography of neurotransmitter receptors using tritium sensitive film. PMID- 6268431 TI - The regulation of glycoprotein synthesis by cAMP in Dictyostelium. PMID- 6268432 TI - Human cell transformation by simian virus 40. Biologic features of cloned lines. PMID- 6268433 TI - Hybridization of a mouse T-cell lymphocyte line (HB1) with a polyoma virus transformed mouse fibroblast line. PMID- 6268434 TI - Schistosoma mansoni: Astiban-induced damage to tegument and the male reproductive system. PMID- 6268435 TI - Electron microscopy of polyps of the colon. I. Comparative study of the epithelial cells of adenomatous and adenopapillary polyps. AB - By comparing the electron-microscopic pictures of adenomatous and adenopapillary polyps, the ultrastructural characteristics of premalignant epithelial dysplasia were studied. In highly differentiated adenomatous polyps, the ratio and the electron-microscopic appearance of absorptive and goblet cells did not differ from the epithelial cells of the normal mucosa of the colon. In the dysplastic regions of adenopapillary polyps, the intensive proliferation in several layers of undifferentiated epithelial cells, and the maturation disorder of absorptive and goblet cells, were observed. Severe changes occurred on the cell membrane as well as atypical vacuoles and dense bodies in the apical regions of the cell membrane. Several inclusion bodies of Leuchtenberger were observed, these being considered an important characteristic of malignant transformation. PMID- 6268436 TI - Polyphosphoinositide metabolism in erythrocytes from spontaneously hypertensive rats. AB - Incorporation of 32P into di- and triphosphoinositides of erythrocytes from 1 month-old spontaneously hypertensive rats was lower, and diphosphoinositide content higher, than in controls. During development of hypertension these initial differences decreased and were even reversed. PMID- 6268437 TI - Quercetin enhances water transport in toad bladder. AB - A highly significant enhancement of the hydrosmotic actions both of vasopressin and of exogenous cAMP was seen in the presence of quercetin. The hypothesis is advanced that quercetin affects the intracellular coupling between Ca++ in cAMP. PMID- 6268438 TI - Na-pump sites in the oviduct of Salamandra salamandra (L.) (Amphibia, Urodela). AB - Using 3H-ouabain autoradiography, Na+-K+-ATPase has been localized on the basolateral membranes of ciliated and nonciliated cells in the oviduct (pars recta, p. convoluta I, II, III) of the European fire salamander, Salamandra salamandra. The mucous and seromucous gland cells of the p. convoluta I, II, III, however, do not show any significant labelling. An asymmetrical distribution of ouabain binding sites is a main feature of transporting epithelia. PMID- 6268439 TI - [Effect of certain neuromediators on segmental mechanisms of vasomotor regulation]. AB - Effect of m-cholinergic and alpha-adrenomimetic compounds on the systems of activation and reduction of spinal vasomotor neurones was studied in experiments on spinal curarized cats. It was shown that stimulation of m-cholino- and alpha adrenoreceptors of the segmental structures produces an inhibition of the neurogenic vascular tone. However, cholino- and adrenomimetic drugs influence the different systems participating in the circulatory neurogenic regulation. PMID- 6268440 TI - [Effect of nonachlazine on the calcium mechanism of regulating coronary artery tone]. PMID- 6268441 TI - [Effect of methanedienone (methandrostenolone) on energy processes and carbohydrate metabolism in rat liver cells]. AB - It was found that methandienone administered through a gastric tube in daily doses of 1 mg/kg of body weight for 20 days induces significant changes in carbohydrate metabolism and in energy processes of the rat liver cell. Methandienone itself enhances glycogenolysis and anaerobic glycolysis, reduces cell respiration and does not affect the intensity and effectiveness of oxidative phosphorylation evaluated with succinate as a substrate. It is suggested that reduction of the cell respiration with concurrent enhancement of anaerobic glycolysis by methandienone seems to be the result of cell metabolism transposition on the oxygen-more-independent pathway. PMID- 6268442 TI - [Research on substances with antiviral activity. XVIII. Bis-amidinohydrazones of N-heterocyclic aromatic dialdehydes]. AB - Some bis-amidinohydrazones of N-heterocyclic aromatic dialdehydes were synthesised and tested in vitro against the MP mutant of the herpes simplex virus type 1 [HSV - I (MP)]. Of the compounds tested, only those with and indole substrate showed some measure of biological activity. PMID- 6268443 TI - Electroencephalographic effects of two short chain ACTH analogues. AB - The effects of two short chain ACTH analogues, tetracosactide 1-24, eptadecapeptide 1-17, on EEG, behaviour and temperature of the rabbit are studied. The behaviour and temperature effects of two compounds are quite similar. The EEG synchronizing action is more evident when tetracosactide 1-24 is administered. This fact suggests that the aminoacids 18-24 might be important in affecting electric cerebral activity. PMID- 6268444 TI - A monoclonal antibody inhibiting rat liver 5'-nucleotidase. PMID- 6268445 TI - Photo-affinity inactivation of gonadotropin releasing hormone receptors. PMID- 6268446 TI - Labelling of the hydrophobic domain of the Na+,K+-ATPase. PMID- 6268447 TI - Study of 'difficult peptides' from Paracoccus cytochrome c-550 and a dolphin cytochrome c. Fast atom bombardment: a new method for molecular weight and sequence determination of peptides. PMID- 6268448 TI - Study on the met-tRNA-binding activity in Krebs-2 cells infected with encephalomyocarditis virus. PMID- 6268449 TI - Effect of the chemotactic peptide on the subsequent superoxide releasing response in human polymorphonuclear leukocytes. PMID- 6268450 TI - (D-Ala2, N-Val5), (D-Ala2, Met5) enkephalins and enkephalinamides. Correlation between biological activity and NMR features. PMID- 6268452 TI - Stimulation of rat fat cell phosphodiesterase by adenosine. PMID- 6268451 TI - Cholera toxin can recouple hormone receptors that are uncoupled from adenylate cyclase. PMID- 6268454 TI - Nucleodisome - a new repeat unit of chromatin revealed in nuclei of pigeon erythrocytes by DNase I digestion. PMID- 6268455 TI - Photoaffinity labelling of MSH receptors reveals a dual role of calcium in melanophore stimulation. PMID- 6268453 TI - Comparative effect of S-adenosyl-homocysteine (SAH) and Sinefungin on tRNA-base methylation in whole cells and in vitro. PMID- 6268456 TI - Characterization of the lipopolysaccharide from the polymyxin-resistant pmrA mutants of Salmonella typhimurium. PMID- 6268457 TI - Purification and properties of the diheme cytochrome (cytochrome c-552) from Pseudomonas perfectomarinus. PMID- 6268459 TI - Compact structure of ribosomal protein S4 in solution as revealed by small-angle x-ray scattering. PMID- 6268458 TI - On the rate limiting step of yeast tRNAPhe aminoacylation. PMID- 6268460 TI - An important role of prostacyclin in porcine thyroid cells in culture. Stimulation and refractoriness of cyclic AMP synthesis and iodine metabolism. PMID- 6268461 TI - Acetylcholine receptor kinetics at slow fiber neuromuscular junctions. AB - Acetylcholine receptors in slow fiber neuromuscular junctions of garter snake (sp. Thamnophis) produced synaptic responses that were more complicated than those observed from twitch fibers. Although the slow fiber miniature end plate currents decayed monoexponentially with time, both the current fluctuations spectrum and the voltage jump end plate current required two temporal components for good theoretical fits. This behavior was accurately accounted for by a generalized version of the three-state kinetic model by del Castillo and Katz. Application of the model allowed not only the rate of channel closing to be estimated, but also the rate of channel opening (from the closed state with acetylcholine bound) and the apparent rate of acetylcholine unbinding from the receptor. The results suggest that at the peak of the miniature end plate current local receptor saturation occurs. PMID- 6268462 TI - Slow cholinergic and peptidergic transmission in sympathetic ganglia. AB - Experiments of voltage-clamped bullfrog sympathetic neurons suggest that the "slow depolarization" produced by orthodromic stimulation, by muscarinic agonists, or by the peptide luteinizing hormone-releasing hormone (LHRH), results from the suppression of a time- and voltage-dependent outward K+ current, the "M current" (IM). This current is activated between -60 and -10mV, with a half maximal activation voltage of -35 mV, a minimum time constant (TM) of 150 ms at 35 mV, and a voltage sensitivity corresponding to a single gating particle with a minimum valency of 4.IM does not show time-dependent inactivation within its activation range and provides the sole potential-sensitive component of the steady outward membrane conductances between -60 and -25 mV. Muscarinic agonists and LHRH selectively depress IM via different receptors, without altering their voltage sensitivity. Although not dependent on external Ca2+ ion, IM is also selectively depressed by Ba2+ ions, so accounting for the cholinomimetic action of Ba2+. It is suggested that IM acts as a braking control on spike discharges and that removal of this control during slow cholinergic and peptidergic transmission provides a unique synaptic tuning mechanism. PMID- 6268463 TI - Transmitter-induced calcium current. AB - Iontophoretic application of serotonin on some neurons of Aplysia causes a slow, voltage-dependent inward current. Experimental evidence indicates that the current is carried by calcium ions: the response to serotonin is unaffected by changes in chloride or potassium concentration, slowly attenuated by sodium-free solutions, reduced in some (although not all) preparations by a low-calcium solution, and blocked by calcium channel blockers. The transmitter-induced calcium current has a voltage sensitivity similar to that of calcium currents in other systems. Intracellular application of cyclic AMP also elicits a voltage dependent inward current. Although cyclic AMP mimics serotonin, pharmacological agents do not have the actions expected if cyclic AMP were mediating the response to serotonin, Phosphodiesterase inhibitors block the responses to both serotonin and cyclic AMP; 5,5'-dithiobis(2-nitrobenzoic acid), and adenylate cyclase inhibitor, and imidazole, a phosphodiesterase activator, do not reduce the serotonin response. Because calcium has many important roles in neuronal activity, including synaptic transmission, the current evoked by serotonin and by cyclic AMP, whether acting independently or as part of the same mechanism, would have important functional consequences. PMID- 6268464 TI - Voltage clamp analysis of inhibitory synaptic action in crayfish stretch receptor neurons. AB - Abdominal stretch receptor neurons of Procambarus clarkii were voltage clamped with two microelectrodes, and the synaptic currents set up by stimulating the inhibitory axons, or by rapid bath application of gamma-aminobutyric acid (GABA), were recorded. The inhibitory postsynaptic current (IPSC) decay was exponential, the time constant of decay being increased by membrane depolarization. The IPSC decay was prolonged by diphenylhydantoin, whereas the IPSC amplitude was depressed by picrotoxin. It is suggested that these effects may reflect slowing of the channel closing and opening rates, respectively. Step clamps applied in the presence of GABA yield currents that show inactivation in the 100 ms time range. This inactivation was shown to reflect chloride movement across the membrane. Step clamp data were used to construct dose-response curves. Diphenylhydantoin shifts the dose-response curve to the left with little change in the maximum response. Picrotoxin shifts the curve to the right with a small reduction in the maximum response. These effects are consistent with the postulated effects on channel opening and closing rates, if GABA normally opens a large portion of the channels. Suitable combinations of picrotoxin and diphenylhydantoin acting together leave the dose-response curve unmodified, as predicted. PMID- 6268465 TI - A comparison of NADPH and cumene hydroperoxide-stimulated lipid peroxidation in mouse hepatic microsomes. PMID- 6268467 TI - Phosphoinositides in the developing inner ear with references to brain, kidney and liver of the mouse. PMID- 6268466 TI - Loss of haem and haemoproteins during the generation of superoxide anion and hydrogen peroxide: a pathway not involving production of carbon monoxide. PMID- 6268468 TI - Molecular geometry of cytochrome c and its peroxidase: a model for biological electron transfer. PMID- 6268469 TI - Enzymic mechanisms of phosphoryl transfer. PMID- 6268470 TI - Prostaglandin E2 increases adenosine 3',5'-monophosphate concentration and binding-site occupancy, and stimulates serotonin-N-acetyltransferase activity in rat pineal glands in vitro. AB - The effects of prostaglandins (PGs) on rat pineal metabolism were examined in vitro. PGE2 (0.01-1 microM) increased the activity of serotonin-N acetyltransferase (SNAT), the stimulation curve exhibiting a maximum at 0.1 microM. PGE1 increased SNAT activity only at the highest dose (1 microM) whereas PGF2 alpha, 15-keto-PGF2 alpha or PGI2 did not affect the enzymic activity. The stimulation of SNAT activity brought about by PGE2 in pineals from ganglionectomized rats was greater than in sham-operated controls at all the doses studied, suggesting that the observed effect is predominantly post synaptic. Only PGE2 significantly increased pineal cAMP accumulation in vitro at doses between 0.01 and 1 microM, and depressed the unoccupied cAMP-binding sites in pineal 900 g supernatants. The total number of cAMP-binding sites remained unaltered after incubation of PGE2. The present observations together with the previously reported NE-induced release of PGs in incubated pineal glands, the occurrence of pineal PG-binding sites and the indomethacin blockade of the nocturnal rise of pineal SNAT and melatonin content, support a role for PGs in the control of melatonin synthesis. PMID- 6268471 TI - In vitro heteroregulation of LH receptors by prolactin and FSH in rat granulosa cells. AB - The purpose of the present study was to further characterize the regulation of LH/hCG receptors by FSH in granulosa cells and test the hypothesis that the LH/hCG receptor levels are heteroregulated by PRL. Granulosa cells from immature hypophysectomized, DES-treated rats were cultured for 2-4 days in defined medium containing androstenedione (10(-7) M) and/or FSH and PRL, after which [125I]iodo hCG binding to the granulosa cells was measured. When granulosa cells were cultured for 2 days (days 0-2) with increasing concentrations of FSH (0.1-100 ng/ml), there was a dose related increase in [125I]iode-hCG binding from a control value of 1.05 +/- 0.2 fmoles/10(6) cells to a maximum of 20 +/- 1.8 fmoles/10(6) cells. The miminum, half-maximum (ED50) and maximum doses of FSH were 0.3, 0.5 and 3 ng/ml, respectively. At concentrations of FSH greater than 3 ng/ml there was a progressive decrease in [125I]-iodo-hCG binding to a low value of 6.1 +/- 1 fmoles/10(6) cells at 100 ng/ml of FSH. No changes in [125I]iodo-hCG binding were observed in response to PRL (1 microgram/ml) during the day 0-2 incubation. When granulosa cells were stimulated for 2 days with 20 ng/ml of FSH, washed, and then recultured for another 2 days (days 2-4) with FSH, the LH/hCG receptor content remained high (F leads to F = 17.4 +/- 2.8 fmoles/10(6) cells). In contrast, when FSH-primed cells were recultured for 2 days without FSH, the [125I]iodo-hCG binding decreased sharply to near control levels (F leads to C = 2.5 +/- 0.2 fmoles/10(6) cells). This marked loss of LH/hCG receptors was largely prevented when FSH primed cells were recultured with PRL (F leads to P = 10.3 +/- 1.5 fmoles/10(6) cells). This stimulatory effect of PRL on [125I]iodo-hCG binding was dose-dependent: minimum, ED50, and maximum doses of PRL were 0.2, 0.5 and 1 microgram/ml, respectively. Scatchard-plot analysis revealed that although the dissociation constant (Kd) of the LH/hCG receptors stimulated by FSH and PRL were of similar high affinity (approximately 8 x 10(-11) M), the maximum binding (Bmax) values in the PRL-treated cells were less. Addition of 10(-7) estradiol together with the PRL did not cause a further increase in Bmax values above that observed with PRL alone. PMID- 6268473 TI - Single-dose tolerance to morphine-induced analgesic and hypoactive effects in infant rats. AB - A single injection of morphine or isotonic saline was administered to rats at either 1, 5, 9, ro 13 days of age. At 26-29 days of age, animals were tested for pain responsivity and activity following either morphine (5 mg/kg) or saline. Animals which received morphine at 1 day of age displayed tolerance at 26 days of age, whereas animals which received morphine at either 5, 9, or 13 days of age failed to display tolerance. This age-dependent change in susceptibility to single-dose morphine tolerance may involve alterations in opiate receptor ontogeny. PMID- 6268472 TI - Modulation of FSH-controlled steroidogenesis in rat granulosa cells: direct in vitro effects of LHRH and ICI-118630. AB - Direct inhibitory effects of LHRH and an LHRH agonist (ICI-118630) on FSH controlled steroidogenic processes in ovarian granulosa cells were characterized in vitro. Over a 2-day culture period in the presence of testosterone (10(-7) M), FSH (3-3 000 ng/ml) caused dose-dependent increases in the aromatase activity of granulosa cells isolated from oestrogen-pretreated immature rats. Progestogen biosynthesis was stimulated in a similar manner. The presence of LHRH (10(-9) - 10(-7) M) in the culture medium inhibited these responses by right-shifting the dose-response curves. Thus the net effect was one of reduced sensitivity to FSH. ICI-118630 was approximately 10 times more effective than LHRH as an inhibitor of aromatase induction and progestogen biosynthesis in response to FSH. Over a 1-h incubation at concentrations up to 10(-7) M, neither decapeptide had a consistent inhibitory effect on FSH-stimulated granulosa cell cAMP formation either in the presence or absence of 1-methyl-3-isobutyl-xanthine (MIX); but during the 2-day culture, ICI-118630 and occasionally LHRH significantly inhibited aromatase induction by cholera toxin and 2 different cAMP analogues. Over the same range of concentrations, each peptide progressively inhibited the stimulatory effect of MIX on FSH-induced aromatase activity and progestogen biosynthesis. Thus LHRH/ICI 118630 can directly modulate FSH-controlled granulosa cell steroidogenesis in vitro via effects on one or more biochemical loci distal to the FSH-receptor coupled adenylate cyclase system. These experiments have implications for the role of a putative LHRH-like ovarian substance(s) in the local co-ordination of follicular development and function. PMID- 6268474 TI - Treatment of infantile spasms with sodium dipropylacetic acid. AB - Eighteen infants with infantile spasms were given sodium dipropylacetate at a dosage of 20mg/kg/day. They were clinically examined before treatment, and again after one to three years of therapy. The short-term clinical response was excellent in four patients, good in eight, poor in four and there was no change in two. At follow-up, two patients were clinically normal, but 10 had severe and six had moderate mental retardation. Seven patients still had residual seizures. Since these results do not differ significantly from those obtained with hormonal treatment, the authors suggest using sodium dipropylacetate (which has less frequent and less severe side-effects than adreno-corticotropic hormone) as the only initial drug, and to use hormonal treatment only in unresponsive patients. PMID- 6268476 TI - Further characterization of a thermosensitive transformation variant of mouse fibroblasts. AB - Temperature-sensitive (ts) variants that express phenotype at low (33 degrees) but not at high (38.5 degrees) temperature were isolated from a mouse fibroblast strain C3H2K cells. Among these variants, cloned ts-12B cells showed at 38.5 degrees a density-dependent inhibition of growth typical of normal fibroblasts cultured in vitro. However, at low temperature they lost this capacity and grew to a higher saturation density. The ts variant was also temperature-sensitive as regards serum requirement: it required a higher concentration of serum for growth at 38.5 degrees than at 33 degrees. However, the cells behaved at both temperatures like the parent strain, possessing anchorage-dependence for growth and fibronectin, whereas they were like transformed cells with respect to release of high fibrinolytic activity. No type-C virus core protein p30 was detected at either temperature. Thus, various parameters of transformation in vitro were independently regulated in these variant cells. PMID- 6268475 TI - Improved diabetic control and hypocholesterolaemic effect induced by long-term dietary supplementation with guar gum in type 2 (insulin-independent) diabetes. AB - The effects of dietary supplementation with granulated guar gum (21 g/day in three divided doses at the main meals), were compared with placebo response during three months in a double-blind, cross-over trial in 11 Type 2 (insulin independent) diabetes. The nine patients who complete the study (two dropped out because of side-effects) showed a significant reduction in both basal and post prandial hyperglycaemia as well as of urinary excretion of glucose during guar gum supplementation. No change in mean bodyweight was observed during the study. Mean fasting and post-prandial plasma insulin levels were similar during both study periods, but the two subjects who received no oral hypoglycaemic agents had lower insulin levels during the guar gum period. Mean serum total- and LDL cholesterol concentrations were significantly lower during the guar gum period, whereas the HDL-cholesterol level remained unchanged. Long-term administration of guar gum induced a sustained improvement in diabetic control in Type 2 diabetes. PMID- 6268478 TI - Immunological reaction between sera from neutron-irradiated W/FU rats and mouse mammary tumor virus. AB - Sera from W/Fu rats from the presence of anti mouse mammary tumor virus (MMTV) antibodies were examined by the use of an immunofluorescence (IF) test and an immune adherence hemagglutination (IAHA) test. Sera from W/Fu rats subjected to neutron irradiation or neutron irradiation followed by grafting of pituitary tumor (MtT) as a source of prolactin gave a positive IF reaction with mouse mammary tumor cells (MMT) producing type-A and type-B virus particles. Nine out of 20 (45.0%) sera from rats given irradiation alone, 17 out of 25 (68.0%) sera from rats subjected to irradiation followed by grafting of MtT and 8 out of 10 (80%) sera from rats given only grafting of MtT gave a positive reaction with the cells, whereas 5 out of 19 (26.3%) sera from normal rats showed a positive reaction with the cells. The specificity of the reaction was confirmed by the distribution pattern of specific fluorescence in MMT cells and by absorption experiments with suitable materials. The results of the IAHA test also showed that some sera from W/Fu rats reacted specifically with purified MMTV, although the incidence of appearance of antibodies in rat sera as detected by IAhA test was low as compared with that detected by IF tests. The IAHA titers of positive rat sera ranged from 1:8 to 1:128. Furthermore, the above results suggest that MtT grafting into W/Fu rats, whether or not they are subjected to neutron irradiation, results in an increase in the frequency of rats carrying antibodies against MMTV. PMID- 6268477 TI - Increased sensitivity of fibroblasts of skin from patients with adenomatosis coli and Peutz-Jegher's syndrome to transformation by murine sarcoma virus. AB - Skin fibroblasts from family members of cases of adenomatosis coli (AC) and Peutz Jegher's syndrome (PJ) were examined for susceptibility to morphological transformation by Moloney murine sarcoma virus (MSV) of rate 78AI cells, which was found in the present study to contain both dualtropic and ecotropic murine leukemia virus (MLV). The fibroblasts from individuals with manifest AC (22 subjects) and manifest PJ (5 subjects) were up to 5 times more susceptible to transformation by rat 78AI-MSV(MLV) than those from normal individuals (7 subjects). Nonmanifest members of AC families (8 subjects) showed various sensitivities: the fibroblasts from 3 family members had a sensitivity as low as that of normal cells, and those of 5 individuals exhibited increased sensitivity similar to that of manifest cases of AC. The AC and PJ cells that were sensitive to 78AI-MSV(MLV) were also susceptible to transformation by other pseudo-types of Moloney MSV, although they were not transformed by infection of standard Moloney MSV. None of the fibroblasts were transformed by xenotropic MLV alone. The tumor promoter 12-O-tetradecanoyl phorbol-13-acetate enhanced transformation by 78AI MSV(MLV) in both AC and normal cells. PMID- 6268479 TI - Production of HBs-antigen by two new human hepatoma cell lines and its enhancement by dexamethasone. PMID- 6268480 TI - [Results of ultrasonographic examinations in diagnosis of carcinoma of the breast (author's transl)]. PMID- 6268481 TI - [In vivo restriction of Escherichia coli-transforming DNA by endonuclease R.M.EcoRI]. AB - Transformation of Escherichia coli K-12 for various chromosomal markers was accomplished by using AB1157 recBC+ strain as a recipient. The yield of transformants was reduced 10-fold, as compared with that obtained in JC7623 recBC sbcB recipient. Elimination of transformation has been obtained for arg, pro, his markers in AB1157 (pSA14) harbouring the R.M.EcoRI coding plasmid. Production of restriction endonuclease in this strain did not affect the efficiency of transformation for thr, leu markers. The presence of pSA25 which is isogenic to pSA14 but devoid of R.M.EcoRI genes has been irrelevant to transformation for leu, arg, pro, his, thr markers. Correlation between the restriction of transformed markers in vivo and in vitro is discussed. PMID- 6268482 TI - [Combination of nephroblastoma and aniridia in a child with congenital deletion of chromosome 11]. PMID- 6268483 TI - [Dynamics of the processes of soil self-purification of pollution from the effluents from animal-breeding farm complexes]. PMID- 6268484 TI - Survey of clinical behavior of patients with borderline epithelial tumors of the ovary. PMID- 6268486 TI - Systemic absorption of conjugated estrogenic cream by the irradiated vagina. PMID- 6268485 TI - Neuroendocrine carcinoma of the cervix: implications for staging and therapy. PMID- 6268487 TI - [Hormone receptors and breast cancer]. PMID- 6268488 TI - Ultrastructural study of chronic myeloid leukemia in blast crisis using myeloperoxidase and acid phosphatase reactions. PMID- 6268489 TI - Abnormal granulation and crystal-like structures in the erythroid cells in a case of multiple myeloma. PMID- 6268490 TI - [Fetal lung maturity]. PMID- 6268491 TI - [Pathophysiology of diarrhea and therapeutic consequences]. PMID- 6268492 TI - [Paget's disease of bone]. PMID- 6268493 TI - Chemoarchitectonics of metencephalon of Testudo elegant. AB - Histoenzymological study of acid phosphatase (GP-AI), 5-nucleotidase (AMP-A), adenosine triphosphatase (ATP-A) and beta-galactosidase (GLAC-A) of the metencephalon of turtle shows a pattern of distribution of enzymes similar to amphibians and mammalian metencephalon which provides indication of homology of the nuclei and tracts such as nucleus raphe, nuclei cerebelli fasciculus longitudinalis medialis, commissura ansulata and internal arcuate fibers. The nerve fibers, tracts and commissures demonstrate strong activity of GLAC-A as demonstrated in frog and bat by the author in previous studies. PMID- 6268494 TI - Effects of fertilizers on eggs of Taenia saginata Goeze, 1782 under field conditions. PMID- 6268495 TI - [Electrophysiologic effects of calcium channel blocking agents on the sinus node function in anesthetized dogs (author's transl)]. AB - The electrophysiologic effects of calcium channel blocking agents, diltiazem, verapamil and nifedipine, on the sinus node function were examined in 43 anesthetized closed-chest dogs in comparison with the effects of propranolol. The parameters of sinus node function, i.e. sinus cycle length (SCL), sinus node recovery time determined by overdrive suppression (SRT), both of which are thought to reflect sinus node automaticity, and sinoatrial conduction time estimated by Strauss method (SACT), were evaluated. Intravenously administered diltiazem (0.2 mg/kg), verapamil (0.1 mg/kg) and propranolol (0.1 approximately 0.2 mg/kg) increased SCL and SRT significantly although the increase of these parameters induced by nifedipine (0.03 mg/kg) was not statistically significant. The calcium channel blocking agents did not significantly affect SACT in contrast with propranolol which showed a prolonging effect. Thus calcium channel blocking agents suppressed sinus node automaticity yet had little effect on sinoatrial conduction. PMID- 6268496 TI - Technique tips: footings. PMID- 6268497 TI - [Transrenal ureteric embolisation. Experimental and clinical results (author's transl)]. AB - Transrenal ureteric embolisation with the tissue adhesive butyl 2-cyano-acrylate mixed with lipiodol and tantalum powder produces rapid and effective occlusion of the ureter. This can be combined with the use of a Gianturco spiral. In an experimental series of eight dogs observed for 54 days, the adhesive disappeared partly in three animals and totally in a further three. Fibrotic ureteric stenosis was observed in three animals. Clinical results were rather better because of the presence of external urinary drainage. Twenty-one ureters in eighteen patients were occluded either unilaterally or bilaterally, and sometimes combined with percutaneous contralateral renal embolisation. After one to four months, the ureter was still occluded in three out of six cases; after five to 17 months, three out of five cases were no longer totally occluded, but in two cases they were still blocked. The procedure is new and suitable for the treatment of otherwise untreatable conditions, such as extensive urinary fistulae, bladder tenesmus and haematuria due to extensive tumours of the minor pelvis. PMID- 6268498 TI - [Problems in the treatment and after care of chronic dermatoses. A clinical study on hametum ointment]. AB - Two groups of patients with endogenous eczema (n = 36) and toxic degenerative eczema (n = 80) were treated with Hametum Salbe and a control preparation. The present results indicate that Hametum Salbe is superior in effectiveness in treatment of atopic dermatitis compared to the control preparation. There was no difference in therapeutical effectiveness in the treatment of primary irritant contact dermatitis. For treatment and interval therapy as well as for long-term treatment of chronic dermatoses Hametum Salbe is a valuable dermatological preparation which can be used without any risk in long-term therapy. PMID- 6268499 TI - [Actovegin therapy of plexus-brachialis paresis following x-ray treatment]. PMID- 6268500 TI - [Cholesterol- and weight reduction with a formula diet containing protein and legumes]. AB - For weight reduction nine healthy subjects received a formula diet rich in protein and dietary fibers. The weight loss was 335 g/day. Cholesterol concentrations dropped about 30% in the course of 14 days. With a daily dose of 75 g protein-mixture the nitrogen-balance was slightly positive. Due to the high fiber content of the formula diet the stool weight was 78 +/- 45 g/day. No changes in blood chemistry and mineral content of urine were observed. PMID- 6268501 TI - [Effect of balneotherapy on the long-term development of degenerative diseases of the lumbar spine with spinal root irritation]. PMID- 6268502 TI - [The role of latent collagenase activation in pathological processes]. PMID- 6268503 TI - Effect of graded doses of PGE2 on pancreatic exocrine secretion of bicarbonate, chymotrypsin and cyclic nucleotides during i.v. infusion of secretin in man. AB - We have previously reported that PGE2 inhibits pancreatic enzyme secretion during Secretin-Caerulein infusion, but differing results have also been reported. In this study 10 tests were performed in 5 healthy volunteers as follows: each subject received secretin (GIH) 2 CU/Kg-h by continuous infusion for 2 hours and, several days later, Secretin at the same dose plus PGE2 (Upjohn) in step-wise doses (0.04-0.08-0.12 gamma/Kg min) increasing every thirty min form 30' to 120' min. Duodenal juice was collected in 10 min samples. The volume of each sample was recorded and bicarbonate, chymotrypsin, cAMP and cGMP contents were determined. Statistical evaluation was performed by Student's "t" test for paired data and the regression test. PGE2 significantly decreased chymotrypsin concentration under Secretin. Both cyclic AMP and GMP Secretin-induced secretions were significantly increased by the highest dose of PGE2. No correlation was found in the behaviour of bicarbonate, chymotrypsin and cyclic nucleotides, but it must be noted that our data concern duodenal contents and not pure pancreatic secretion. PMID- 6268504 TI - The intestinal enzymatic biotransformation system: potential role in protection from colon cancer. PMID- 6268505 TI - Effect of testosterone on the hypothalamic-pituitary-testicular axis of the old male rat. AB - Old rats show lower serum testosterone, a lower increase in serum LH either after orchidectomy or after LHRH stimulation, and a lower number of hCG binding sites in testis, compared to younger controls. Treatment with testosterone for 5 to 6 weeks was followed by an increment in the androgen serum levels of about 70% in adult, and of 170% in old animals, a reduction to about one half testicular weight in both groups, and an inhibition of similar magnitudes in the LH increase that followed castration or LHRH stimulation. Testosterone treatment reduced the binding sites for hCG in testis of young rats but did not correct the already low values observed in the old animals. It is suggested that similarities and differences occur in the hypothalamic-pituitary-testicular axis of young and old animals and that differences could be due to changes in set points regulation of the system and/or some intrinsic modification of the hormone producing mechanisms. PMID- 6268506 TI - Chronic and acute stress interrelationship: corticosterone response. PMID- 6268507 TI - Proteolytic activation of Ca2+-dependent cyclic nucleotide phosphodiesterase from Escherichia coli. AB - Ca2+ -dependent cyclic nucleotide phosphodiesterase from Escherichia coli was activated by limited proteolysis. The proteolytically activated enzyme lost the sensitivity to Ca2+ but its kinetic properties were not altered. PMID- 6268508 TI - Structure and biosynthesis of peptides related to corticotrophin and lipotrophin. PMID- 6268509 TI - Lipo-corticotropic hormones and Cushing's disease. PMID- 6268510 TI - [Cellular localization of peptides derived from pro-opiocortin in the normal human adenohypophysis and in tumors of Cushing's disease]. AB - As early as 1932, basophil cells have been considered to be involved in the corticotropic and melanotropic functions due to their proliferation during Cushing's disease. Later on, opposite opinions were held and other cells suggested to be implied in the tumor process: chromophobe, acidophil or even follicular cells. Moreover, new categories of basophil cells have been evidenced through sophisticated staining methods, in animal and human pituitaries. At the same time, the prevalent dogma 'one hormone-one cell' raised the problem of the search for both a corticotroph and a melanotroph in the human pituitary, which is devoid of an intermediate lobe. Since 1960, immunocytochemistry became a reliable method and simultaneously new peptides have been found. However, these peptides share common sequences of amino acids, thus raising questions as to the specificity of the antisera. Most authors mention the reaction to the basophil cells previously considered as melanotrophs and called beta or R [here beta(R)]. These large rounded cells, showing red granules after Alcian blue-PAS staining, are mostly located in the median area of the anterior lobe, in the cystiform zone and in cell cords invading the neural lobe. In the fetal pituitary, reactivity is observed either in some differentiated beta(R) cells or, earlier, in chromophobe cells. The question is now raised whether one cell may contain several peptides and, in this case, whether the different peptides are carried by the same granule. Technical procedures using numerous antisera on serial sections have shown associations at the level of a given cell (and of a given granule under the electron microscope). However, dissociations are also to be noticed, as far as ACTH and beta-MSH (adult) and more particularly alpha-MSH (adult and fetus) are concerned. PMID- 6268512 TI - [Lipocorticotropic peptides in Cushing's disease: in vitro studies]. AB - The immunologic patterns of 3 human pituitary adenomas of Cushing's disease have been studied after gel exclusion chromatography (Sephadex G-50). The immunologic characteristics were examined with three radioimmunoassays specific for human corticotropin (ACTH), lipotropin (LPH) and beta-endorphin (beta-End). In cell tumor extracts, chromatographic peaks corresponding to beta-LPH, gamma-LPH, beta End and ACTH were identified. The ACTH/beta-LP-beta-End ratio was 1 in the 3 cases. Additionally, in the 3 cases, a chromatographic peak, partially cross reacting in the beta-End assay, was eluted after beta-End, thus suggesting the presence of a fragment of the molecule. In 1 case, a peak of large molecular weight material with N- and C-terminal beta-LPH and ACTH immunoreactivity was observed, which corresponded to the precursor material. The release and the effects of various stimuli were studied on dispersed tumor cells in primary culture. The tumor cells had a biphasic basal secretion rate with a rapid increase of ACTH/beta-LPH-beta-End in the culture medium during the first 2 h. Then the release, studied during 2 days, was slower. Chromatographic studies showed that the beta-LPH/beta-End ratio was 0.8 in the cells and 0.3 in the medium, due essentially to the release of beta-End and beta-End-like materials. The cells released ACTH and beta-LPH-beta-End in equimolar ratio after stimulation with arginine vasopressin (AVP). The maximum effect was obtained with 10(-6) M AVP (D50 = 1 10(-9) M). Dibutyryl cyclic AMP (2. 10(-3) M) induced maximal release of ACTH/beta-LPH-beta-End. This stimulation was suppressed by a 48-hour preincubation with dexamethasone (10(-8)-10(-6) M). There was no effect of TRH and LH-RH on cell release. Dopamine (10(-6) M) specifically blocked the release of ACTH/beta-LPH-beta-End in 1 case. These data showed (a) heterogeneity of chromatographic profiles from case to case; (b) the presence of material in the tumor, cell extracts and culture medium corresponding to fragment(s) of beta End; (c) culture studies demonstrated that tumor cells remain responsive to AVP stimulation and dexamethasone suppression, and (d) the dopamine inhibition of ACTH and beta-End release needs further investigation. PMID- 6268513 TI - In vitro secretion of ACTH, beta-endorphin and beta-lipotropin in Cushing's disease and Nelson's syndrome. AB - Tissue from histologically confirmed ACTH cell adenomas in Cushing's disease (CD) and Nelson's syndrome (NS) was gained by transsphenoidal surgery. Combined enzymatic and mechanic agitation of tumor tissue yielded a cell suspension. Aliquots of the cell suspension were transferred to superfusion chambers immediately after isolation and investigated for ACTH and beta-endorphin production. Feedback action of cortisol (CO) and dexamethasone on basal hormone production and on lysine vasopressin (LVP) induced ACTH secretion were studied. Adenomatous tissue and anterior lobe tissue from the same patient in CD could be investigated simultaneously in 4 cases. The paraadenomatous tissue showed depression of basal and LVP-induced ACTH secretion. In all adenomatous tissues investigated there was missing or reduced suppression of basal ACTH secretion by physiological levels of CO. CO not only failed to suppress LVP-induced ACTH secretion but also seemed to enhance LVP stimulation in some experiments. This study confirms former results, that a missing or inversed feedback action or glucocorticoids in adenoma cells is a mechanism involved in the pathological ACTH secretion in CD and NS. Bioassayable and immunoreactive ACTH from media of superfusion and short-term static incubation were compared with beta-endorphin and beta-LPH in an assay detecting these two peptides with equimolar sensitivity. Secretory patterns were basically parallel but great differences showed in quantities of hormones secreted. In addition, Sephadex G-50 gel chromatography was performed to separate beta-endorphin from beta-LPH and to calculate the ratios. These profiles show great variations between different adenomas. PMID- 6268511 TI - [Hypothalamic control of ACTH secretion]. AB - The hypothalamic regulation of ACTH secretion has been reviewed. Recent biochemical investigations on corticotropin-releasing factor (CRF) suggest that CRF is present in the hypothalamus under two or more different molecular weight forms, their structure being not elucidated yet. Vasopressin has a CRF-like activity. However, contradictory results have been reported on the role of AVP as a physiological CRF. The synthesis of CRF appears to occur in a large hypothalamic area outside the median eminence. CRF-carrying fibers are thought to pass through the lateral retrochiasmatic area and project on the hypophysial portal vessels at the junction between the pituitary stalk and the median eminence. Conflicting data have been published on the influence of monoamines on ACTH secretion. In the dog, ACTH release is inhibited by the alpha-adrenergic receptors, this effect being not as clearly demonstrated in other species. The stimulation of nicotinic and muscarinic receptors followed by increased ACTH secretion. Glucocorticoids appear to lower ACTH secretion through an action at both the hypothalamic and pituitary levels. PMID- 6268514 TI - ACTH, LPH, and beta-endorphin secretion from perfused isolated human pituitary tumour cells in vitro. PMID- 6268515 TI - [Ectopic secretion of ACTH and of related peptides (LPHs, beta-endorphin, "16K"). Evidence for a common precursor]. AB - Studies in the experimental mouse pituitary tumor cell line AtT-20/D-16-v have recently shown that ACTH, the lipotropins (beta- and gamma-LPH), beta-endorphin (beta-End) and the 16-K fragment are synthesized through a common precursor molecule which is a 31,000 glycopeptide (pro-ACTH/endorphin). We have investigated whether such a biosynthetic model might exist in man. Radioimmunoassays have been developed against human ACTH, N-terminal LPH, beta End or C-terminal beta-LPH, C-terminal gamma-LPH, and the 16-K fragment or N terminal pro-ACTH/endorphin. These radioimmunoassays were used to examine various human samples before and after gel fractionation in ordinary or denaturing buffers. Medium DMS-79, in which human small cell carcinoma cells derived from a lung cancer were cultured, was shown to contain molecules identical to gamma-LPH, beta-LPH, beta-End and ACTH. In addition, it also contained a high molecular weight material with LPH, beta-End, and ACTH immunoreactivity. These three immunoreactivities could not be dissociated under denaturing conditions (6 M guanidine-HCl), and were all absorbed on an ACTH-purified anti-(1-24)-ACTH affinity column. Medium DMS-79 also contained high molecular weight calcitonin immunoreactivity that was not absorbed on the (1-24)-ACTH affinity column and therefore was not part of the pro-ACTH/endorphin molecule. Extracts from two pheochromocytomas responsible for the ectopic ACTH syndrome were found to contain, in addition to ACTH, large amounts of gamma-LPH and beta-End. High levels of beta-LPH and beta-End were also present in the plasma from a patient with the ectopic ACTH syndrome due to pancreatic carcinoma. Plasma immunoreactive 16-K fragment was increased in another patient with this syndrome. These results indicate that a biosynthetic model similar to that described in the AtT-20/D-16-v mouse tumor cell line also exists in man. Tumors responsible for the ectopic ACTH syndrome provide a unique source to study this model in man. PMID- 6268516 TI - Circadian and ultradian variations of ACTH and cortisol secretion. PMID- 6268517 TI - Late onset adrenal hyperplasia (21-hydroxylase deficiency): 17-OH progesterone response to ACTH stimulation and HLA typing. A family study. PMID- 6268518 TI - Electronic, steric, and hydrophobic factors influencing the action of enkephalin like peptides on opiate receptors. AB - The requirements of opiate receptors for electronic, steric, and hydrophobic properties of the amino acids in Pos. 4 and 5 of enkephalin-like peptides were studied. A series of [D-Ala2]-enkephalins containing carboranylalanine, adamantylalanine, t-butylglycine and p-nitrophenylalanine were synthesized and their pharmacological activities in the guinea pig ileum and their naloxone displacement in rat brain homogenates determined. An electronegative (-E) aromatic character of the amino acid in Pos. 4 strongly enhanced potency, overruling steric effects. The enhancement was not caused by exceptional enzyme resistance. Amino acid in Pos. 5 contributed to potency mainly through its effect on overall hydrophobicity. The two C-terminal amino acids seem to function as potentiator and address elements in the enkephalins. PMID- 6268519 TI - Glucagon: structure-function relationships investigated by sequence deletions. AB - A series of glucagon analogues, des-(1-4)-glucagon, des-(5-9)-glucagon, des-(10 15)-glucagon, des-(16-21)-glucagon, des-(22-26)-glucagon and des-(27-29) glucagon, were prepared by condensation of synthetic fragments and characterized biologically and immunologically. Fully synthetic glucagon was also characterized. The potencies with regard to glucagon receptor binding in purified rat liver plasma membranes were, in decreasing order: synthetic glucagon 108%, des-(1-4)-glucagon 5.7%, des-(27-29)-glucagon 0.92%, des-(5-9)-glucagon 0.47%, des-(10-15)-glucagon 0.0028%, des-(16-21)-glucagon 0.0017% and des-(22-26) glucagon 0.00060% relative to that of natural porcine glucagon. Des-(27-29) glucagon was the only analogue that activated the adenylate cyclase in rat liver plasma membranes or stimulated the lipolysis in isolated free fat cells from rat epididymal fat pad. The potencies were 0.16% and 0.20% of that of glucagon, respectively. Des-(1-4)-glucagon was a glucagon antagonist in the adenylate cyclase assay. The immunoreactivities of the glucagon analogues were determined with two commonly used anti-glucagon sera, K 5563 and K 4023, directed towards the C-terminus and some segment in the sequence 2-23, respectively. In the K 5563 assay, des-(27-29)-glucagon and des-(22-26)-glucagon had potencies of 0.0009% and less than 0.09% of that of glucagon, respectively. The remaining analogues had potencies varying from 45% to 141% of that of glucagon. In the K 4023 assay, the analogues showed a non-linear dilution effect. The combined results indicate a partition within the glucagon molecule with regard to receptor binding and adenylate cyclase activation. The region 10-26 appears to be the most important for receptor binding, whereas 1-4 is essential for adenylate cyclase activation. The C-terminal segment 27-29 is important for the maintenance of full receptor binding but non-essential for adenylate cyclase activation. PMID- 6268520 TI - Hormonal properties of avidin-biotinylinsulin and avidin-biotinylcorticotropin complexes. AB - In connection with the development of affinity columns (based on the avidin biotin interaction) for retrieval of peptide and protein hormone receptors, the hormonal properties of a number of avidin-biotinylinsulin and avidin bioinylcorticotropin complexes were examined. Of particular interest was an evaluation of streptavidin as a ligand for the attachment of biotinylated hormones to solid supports and its possible advantage over SpHPP-avidin (S = succinoylated; pHPP = 3-(p-hydroxyphenyl)propionyl). As concerns binding kinetics using rat liver plasma membranes, streptavidin was found superior to avidin since it does not display apparently nonsaturable binding. Scatchard analyses of the binding of 125I-streptavidin, 125I-S-streptavidin and 125I-SpHPP-avidin to rat liver plasma membranes gave KD value of 6.7, 13.2, and 10.6 nM respectively. The binding was saturable and the unlabeled proteins competed with their labeled counterparts for the membrane binding sites. Biotinylinsulin, attached to either streptavidin or SpHPP-avidin was able to compete for 125I-insulin-binding sites on rat liver plasma membranes though somewhat larger concentrations of the complexes than of insulin were required to achieve comparable inhibition. The ID50 values for insulin and the biotinylinsulin complexes were 5 and 80 nM respectively. Biotinylcorticotropin was found to be a more effective activator of particulate rat adrenal adenylate cyclase when complexed with unmodified avidin than with streptavidin, S-streptavidin or SpHPP-avidin. PMID- 6268521 TI - The binding of nucleotides and metal ions to elongation factor Tu from Bacillus stearothermophilus as studied by equilibrium dialysis. AB - EF-Tu from B. stearothermophilus binds divalent metal ions even in the absence of guanine nucleotides. The association constants necessary for characterizing the multiple equilibria between EF-Tu, GDP and the divalent ions magnesium and manganese were determined by equilibrium dialysis. The constants are 4.6 X 10(4) M-1 and 5.4 X 10(5) M-1 for the binding of Mg2 and 1.0 X 10(5) M-1 and 1.1 X 10(6) M-1 for the binding of Mn2 to EF-Tu and EF-Tu . GDP, respectively. In the absence of divalent ions EF-Tu binds GMP, GDP and GTP with association constants of 3 x 10(3) M-1, 1.7 x 10(7) M-1 and 1.3 x 10(6) M-1, respectively. The binding of GDP in the presence of metal ions is an order of magnitude stronger than in the absence of metal ions. PMID- 6268522 TI - Comparison of Ehrlich ascites tumour and mouse liver cells by analytical subcellular fractionation combined with a sensitive computational method for data analysis. AB - A simple method of analytical subcellular fractionation, combined with a sensitive computational method for data analysis and presentation, has been used to reinvestigate the distribution and relative amounts of several enzymes in the cytoplasmic and plasma membranes of two different cell types: one is a neoplastic, transformed cell type (Ehrlich ascites tumour cells), the other an untransformed, highly differentiated cell type (liver hepatocytes plus Kupffer and endothelial cells). In general the distribution of the enzymes in particular membranes is similar in the two cell types, however the relative amounts differ. Ehrlich ascites tumour cells have a higher specific activity of galactosyltransferase and ouabain-sensitive (Na,K)ATPase, while liver cells have higher glucose-6-phosphatase, 5'-nucleotidase and succinate dehydrogenase activity. These differences appear to be correlated with morphological and, in some cases, functional differences between the two cell types. PMID- 6268523 TI - Establishing a countywide community support system for mental health care. PMID- 6268524 TI - Myofibroblasts in human pathology. PMID- 6268525 TI - Mullerian adenosarcoma of the uterine cervix. AB - We present a tumor of the uterine cervix that was composed of histologically benign glandular epithelium and a malignant stromal component, justifying the term mullerian adenosarcoma. Ultrastructurally the stromal cells resemble the endometrial stromal cells, the tumor cells of an endolymphatic stromal myosis of the uterine cervix, and the stromal cells of a stromomyoma of the uterus. In addition there is evidence strongly suggesting a differentiation toward smooth muscle. The patient exhibited no evidence of disease one year after surgery. PMID- 6268526 TI - Post-transplantation pancreatitis associated with cytomegalovirus (report of a case). AB - Cytomegalovirus inclusions were identified at autopsy in the pancreas and skin of a patient with acute pancreatitis and herpes zoster who had had a renal transplant. No inclusions were found in any of the other organs examined. Etiologic implications are discussed. PMID- 6268527 TI - Effect of certain metabolites & proteins- on production of superoxide radical by Nishikimi's reaction. PMID- 6268528 TI - [Experiences with the ELISA at the serodiagnosis of infections with viruses of the herpes-group (author's transl)]. AB - A commercially available and standardized enzymeimmunoassay was applied at 737 patients in order to diagnose immunologically a recent or reactivated infection with Herpes simplex, Herpes zoster V. and/or Cytomegalovirus. During this course of investigation rises or falls of the titer of virus specific IgG between the range of 1 : 320, 1 : 1280 and greater than or equal to 1 : 5120 turned out to mark mainly recent infections with one of the three herpes viruses. Statistical evaluations of the tests performed proved the elevated sensitivity of the IgG ELISA as compared with the complement binding reaction. The range of specificity of the two tests was similar. A significant titer of IgM (greater than or equal to 1 : 40) as a marker of a recent infection with one of the three herpes viruses could only be demonstrated at 13-19% of the cases of recent herpes viral infection. Controls of the sera with a significant virus specific IgM-titer in the ELISA by sucrose gradient centrifugation or with a reference-ELISA confirmed their virus specific mu-specificity in almost all of the cases (96%). PMID- 6268529 TI - Adenosine deaminase activity and superoxide formation during phagocytosis and membrane perturbation of macrophages. AB - During phagocytosis and membrane perturbation, mouse macrophages generate superoxide in direct proportion to their intracellular adenosine deaminase activity. It is proposed that since adenosine deaminase controls the amount of substrate available to xanthine oxidase, and the latter produces superoxide during turnover of its substrates, the purine salvage pathway is an important contributor to the superoxide requirement of macrophages. It is further proposed that this may be the basis for the mechanism of the association of adenosine deaminase deficiency with immunodeficiency. PMID- 6268530 TI - Transient cyclic AMP accumulation during antibody-dependent cytotoxicity mediated by monocytes and neutrophils. PMID- 6268531 TI - Hapten-induced changes in pig anti-dansyl antibodies revealed by EPR spectra of spin-labelled antibodies. AB - Pig anti-Dns antibodies were labelled by 2, 2, 6, 6- tetramethyl-N1 oxylpiperidine-4-amino (N-dichlorotriazine) (label SL I) or by 4-amino-2,2,6,6 tetramethyl-piperidine-N1-oxyl (label SL II). SL I presumably reacted with Fab parts, whereas SL II was attached to the carbohydrate moiety of the Fc part of the antibody molecule. The new method of intramolecular mobility estimation based on viscosity-dependent correlation times of the N-O group of spin-labelled proteins was used, making it possible to separate the correlation times of the spin-label relative to the protein carrier (tauR) and of the labelled protein itself (tauM). The altered shape of the EPR spectrum observed upon binding of epsilon-Dns-lysine indicates that the relative fluctuations of the liganded antibody domains within the Fab part are reduced. The character of temperature dependence of the correlation times of the labelled antibody changed upon hapten binding as well, suggesting an altered interaction between antibody subunits. Evidence of hapten-induced changes of both tauR and tauM was obtained at 1 degrees C and 5 degree C using the label SL II bound to the Fc part. The character of the changes can be interpreted in terms of mobilization of the domains and of altered interaction between labelled carbohydrate and the protein moiety. At 5 degree C the addition of 3% of D2O to the antibody labelled by SL II brought about a substantial effect qualitatively similar to that induced by the hapten. PMID- 6268532 TI - Comparative effect of amphotericin B on Rhizoctonia sp., Paecilomyces lilacinus & Fusarium solani in vitro & in experimental keratitis. PMID- 6268533 TI - Acid phosphatase & 5'-nucleotidase activity in the brain of experimentally induced hyperphenylketonuric squirrels Funambulus palmarum. PMID- 6268534 TI - Effect of ACTH, heparin & salicylate on blood coagulation. PMID- 6268535 TI - Pathology of experimental nephrosis-nephritis in chicks induced by infectious bronchitis virus. PMID- 6268536 TI - Effect of dielectric discharge on drug treated mammalian cells. PMID- 6268537 TI - Enzymatic evaluation of bovine follicular fluid as influenced by size & presence of corpus luteum. PMID- 6268538 TI - Prevalence of poliovirus antibodies in healthy children of Ahmedabad. PMID- 6268540 TI - [Important metabolic parameters in the peripartum period as affected by peridural anesthesia]. AB - In a clinical study we compared two groups of healthy patients at term: - 10 patients received no analgesics or very small doses of pethidine (control group) during the course of labour, - 17 patients were given CO2-bupivacaine via epidural catheter because they asked for it and because their obstetricians prescribed it (CEDA-group). After giving the same infusion solution of 120 ml/h 5% half-isotonic fructose to all the parturients, the following biochemical parameters were measured at the beginning and at the end of the first stage of labour, at delivery, and two hours later: Blood gases and acid-base status, blood sugar, lactate, betahydroxybutyric acid, ACTH, cortisol, hematocrit, electrolytes, and serum osmolality. The above mentioned parameters, except electrolytes and serum osmolality, were also determined in umbilical-cord blood immediately after delivery. In the labour ward, infants were observed and their capillary blood gases, acid-bases status, and blood sugar were measured 30, 60, and 120 minutes after birth. Lactate, betahydroxybutyric acid, ACTH, and cortisol levels rose significantly until delivery in both of the groups; significant differences between the two groups could be seen in blood gases, blood sugar, and ACTH levels. In the umbilical cord there were only significant differences in blood sugar. In summary it can be concluded that although labour pain can be controlled by epidural analgesia, the stress of labour is only influenced by different analgesic methods to a certain degree. PMID- 6268539 TI - Deleterious effects of endotoxin on cultured endothelial cells: an in vitro model of vascular injury. AB - The effects of endotoxin-triggered granulocytes on the viability of endothelial cells in vitro was investigated. Endotoxin or its lipid A component caused granulocytes to adhere to and significantly damage cultured endothelial cells. Fresh serum is not necessary but does amplify both adherence and endothelial injury. Much of the endothelial injury was inhibited by free-radical scavengers or by blocking granulocyte adhesion to endothelial cells and appears to result from free radical production by the stimulated granulocyte. Studies in this model suggest a pathogenic role for the endotoxin-triggered granulocyte in the Shwartzman reaction and perhaps related clinical disorders. PMID- 6268541 TI - Dynamic bone scanning in fractures. AB - In 20 cases routine static bone scans were no value in the detection of delayed fracture healing. Using the 7.5-15 min net uptake of technetium labelled phosphate, disturbed fracture healing was detected in a series, of 37 cases. Normally healing fractures had an increase of 3 per cent per month and delayed unions less than half that amount. Non-unions had no net uptake. PMID- 6268542 TI - Basis of the specificity of rodent trypanosomes for their natural hosts. AB - The strong natural insusceptibility of mice to infection with the rat-specific Trypanosoma lewisi was investigated in a variety of mouse strains. Parasite elimination by all strains was similar involving a lag phase of about 7 h of constant parasitemia followed by rapid clearance (half-times of 55 and 130 min in different strains). In vitro cultures were utilized to determine whether mouse cells and serum were inherently deficient in supporting T. lewisi or, alternatively, toxic for the parasite; neither was found to be the case. In attempts to prolong T. lewisi survival and growth, mice were treated with various preparations, including T. lewisi sonicates, rabbit antiserum against mouse macrophages, silica dust, normal rat and rabbit sera and crude immunoglobulin fractions, and combinations of silica dust and serum or immunoglobulin fractions. The most striking effects were obtained with combinations of silica dust and serum, resulting in extensive T. lewisi growth and death of a portion of the infected mice. These results, together with microscopic observations, suggested that the principal mechanism responsible for murine resistance to heterologous trypanosomes is a type of antibody-dependent, cell-mediated immunity involving granulocytes and (probably) platelets. PMID- 6268543 TI - Diarrhea in lambs: experimental infections with enterotoxigenic Escherichia coli, rotavirus, and Cryptosporidium sp. AB - Thirteen gnotobiotic lambs, aged from a few hours to 8 days, were inoculated orally with single infections of enterotoxigenic Escherichia coli (ETEC) (four animals), lamb rotavirus (five animals), and Cryptosporidium (four animals). Six gnotobiotic and two specific-pathogen-free lambs were co-inoculated with either rotavirus and ETEC (four animals), rotavirus and Cryptosporidium (two animals), or ETEC and Cryptosporidium (two animals). Lambs 4 days of age and older became only subclinically infected with either rotavirus, ETEC (08:K87:K99 ST+), or both enteropathogens given simultaneously. Six-day-old lambs inoculated with Cryptosporidium became extremely depressed, anorectic, and had intermittent diarrhea. There was no difference in the clinical manifestations, level of disaccharidase activity in the small intestine, or extent of histological damage between lambs inoculated with Cryptosporidium alone or together with either of the other two agents. The results indicate that under the conditions of these experiments, lambs become clinically resistant to infection with ETEC, rotavirus, or both agents together, by 4 days after birth, whereas lambs 2 days old or younger were clinically susceptible to infection by these agents. In contrast, they remained clinically susceptible to infection with Cryptosporidium up to at least 6 days of age. Cryptosporidium infections were not aggravated by coinfection with either ETEC or rotavirus. PMID- 6268545 TI - Differentiation of members of the human herpesviridae family by radioimmunoassay. AB - Many individuals who are seronegative for one member of the human Herpesviridae family are strongly seropositive for other members. Using sera from such individuals, the radioimmunoassay technique demonstrated absence of antigen antibody cross-reactions between varicella-zoster virus (VZV) and herpes simplex virus (HSV) at levels of less than one part in 1,000. Sera containing antibody to both HSV and VZV were absorbed with antigens of one agent without significantly altering the amount of remaining antibody to the other antigen. This further suggests that HSV and VZV do not share a common antigen. The same radioimmunoassay technique and serum absorption method that revealed no serological cross-reactions between HSV and VZV revealed the expected cross reaction between HSV type 1 (HSV-1) and HSV-2. Reciprocally absorbed anti-HSV-1 and anti-HSV 2 sera were able to differentiate the two HSV types reliably. No cross-reactions were seen between cytomegalovirus, VZV, and HSV or between Epstein-Barr virus, VZV, and HSV. We postulate that heterotypic antibody responses sometimes observed for VZV after primary infections by HSV may not be due to shared antigens, but to activation of latent VZV infections, release of new VZV antigens, and consequent stimulation of new antibody production to VZV. PMID- 6268544 TI - Effect of fractions of Ethiopian And Norwegian colostrum on rotavirus and Escherichia coli heat-labile enterotoxin. AB - Samples of colostrum from both Ethiopian and Norwegian women contained antirotavirus activities of immunoglobulin and non-immunoglobulin nature. No significant differences in rotavirus immunoglobulin A or in rotavirus-inhibiting activity were found between samples from the two countries. The non immunoglobulin inhibitory activity was trypsin sensitive and heat stable (100 degrees C for 10 min). Escherichia coli heat-labile enterotoxin antibodies were measured in the colostrum samples by enzyme-linked immunosorbent assay. No E. coli enterotoxin-specific immunoglobulin A was detected, possibly due to the high background caused by the nonspecific adsorption of immunoglobulin A to the enzyme linked immunosorbent assay plates in the absence of toxin. A total of 5 of 15 Ethiopian colostrum samples and 0 of 11 Norwegian colostrum samples neutralized the effect of E. coli heat-labile enterotoxin on YI adrenal cells. Both the Ethiopian and the Norwegian colostrum samples contained a non-immunoglobulin enterotoxin-inhibitory activity when the toxin was measured by enzyme-linked immunosorbent assay. This inhibitory activity was not trypsin sensitive, and extraction by chloroform-methanol indicated that the inhibitor was of a lipid nature. PMID- 6268546 TI - Inactivation of varicella zoster virus in vitro: effect of leukocytes and specific antibody. AB - Inactivation of varicella zoster virus in vitro by nonadherent, mononuclear peripheral blood leukocytes and antibody is described. When leukocytes and specific antibody were incubated with this virus, marked inactivation of the virus occurred. In contrast, leukocytes alone or with serum devoid of varicella zoster antibody caused only a small degree of inactivation of varicella zoster virus. The leukocytes involved appeared not to be monocyte-macrophages or T or B lymphocytes, and only minute amounts of specific antibody were required. We had found previously that leukocytes from unsensitized (varicella susceptible) as well as sensitized (varicella immune) donors could cause this reaction. We therefore propose that the reaction may be a form of antibody-dependent cellular cytotoxicity, as has been described for 51Cr release by lymphoid (K) cells for other herpesviruses. PMID- 6268547 TI - Susceptibility of mice to rotavirus infection: effects of age and administration of corticosteroids. AB - We examined susceptibility to the murine rotavirus, epizootic diarrhea of infant mice virus (EDIM), in normal suckling and weaned mice and in suckling mice treated with glucocorticoids. Normal mice 1 to 40 days old were inoculated by gastrin intubation with high doses of EDIM and subsequently evaluated for rotavirus infection by solid-phase radioimmunoassay, by electron microscopy of intestinal tissue sections or by both. Radioimmunoassay and electron microscopy showed a concordance of 89.5% in the detection of rotavirus infection. After a period of low susceptibility to EDIM infection during the first 3 days after birth (23%), susceptibility was high for the next 11 days (95%), but decreased abruptly as mice approached weaning (41% on days 15 through 17). Mice 34 days or older did not develop EDIM infection after inoculation, but rotavirus antigen was detected in 12% of uninoculated mothers nursing inoculated litters. Administration of cortisone acetate to 8-day-old mice induced partial intestinal maturation prematurely. At 3 to 6 days after cortisone acetate treatment, susceptibility to EDIM infection decreased to 60% compared with 94% in age matched controls. Our data suggest (i) that susceptibility of mice to EDIM infection is age dependent, decreasing in concert with intestinal maturation, and (ii) that glucocorticoids, which induce premature partial intestinal maturation, modulate susceptibility of mice to EDIM. PMID- 6268548 TI - Immuno-electron microscopic study on the antigenicity of tubular structures associated with human rotavirus. AB - Tubular structures associated with human rotavirus were antigenically related to the single-capsid layered particles having only an inner capsid of the virus because they were agglutinated by heterologous bovine rotavirus antiserum. PMID- 6268549 TI - Extracellular enzymes of Legionella pneumophila. AB - All strains of Legionella pneumophila tested produced detectable levels of extracellular protease, phosphatase, lipase, deoxyribonuclease, ribonuclease, and beta-lactamase activity. Weak starch hydrolysis was also demonstrated for all strains. Elastase, collagenase, phospholipase C, hyaluronidase, chondroitinase, neuraminidase, or coagulase were not detected in any of these laboratory maintained strains. PMID- 6268550 TI - Inhibition of the mitotic response in regenerating mouse liver during viral hepatitis. AB - Viral hepatitis caused by infection with murine hepatitis virus strain A59 has been shown to affect the mitotic response after partial hepatectomy in mice. Normal mice showed a delayed response, whereas nude mice did not show any response, even 5 days after partial hepatectomy. PMID- 6268551 TI - Quality control studies of 99mTc-labeled radiopharmaceuticals by high-performance liquid chromatography. PMID- 6268552 TI - Inter-individual differences in oxidative benzo(a)pyrene metabolism by normal and tumorous surgical lung specimens from 105 lung cancer patients. PMID- 6268553 TI - Antibodies to Epstein-Barr virus-specific antigens in patients with hairy-cell leukemia. AB - Antibody titers to Epstein-Barr virus (EBV)-specific antigens of 19 patients with hairy-cell leukemia (HCL) were markedly elevated. All patients showed high titers of IgG anti-viral capsid antigen (VCA) reactivity equal to or greater than 320 (reciprocal titer). The anti-VCA reciprocal geometric mean titer (GTM) was 1106 in contrast to a GMT of 80 for healthy controls (p less than 0.001). No IgM anti VCA antibody was detected, but three patients had IgA anti-VCA antibodies. Fourteen patients had elevated anti-early antigen (EA) titers (GMT = 177) which were indicative of active infections with EBV. Seven of the 14 patients demonstrated the diffuse component antibody of the early antigen (EA) complex at a GMT of 98. Anti-Epstein-Barr virus nuclear antigen (EBNA) was detected in sera of 16 patients (GMT = 64, controls GMT = 79). It is noteworthy that three patients with anti-VCA titers lacked anti-EBNA titers. These anti-body responses suggest that immunodeficiency secondary to HCL allowed reactivation of the virus. PMID- 6268554 TI - Generation in vitro of EBV-induced specific cytotoxic T cells in autologous serum avoids complications due to self-preferred foetal calf serum-specific T-cell cytotoxicity. AB - A previous report has established that in cultures of human mononuclear leukocytes, foetal calf serum (FCS) is capable of generating high levels of T cells preferentially cytotoxic for the autologous lymphoblastoid cell line (LCL). The present study compared the capacity of Epstein-Barr virus (EBV) to generate cytotoxic T cells in cultures of mononuclear cells grown in FCS in this system. Five EBV-seropositive and three seronegative donors were used and cultures were harvested at 14 days. With cultures from seropositive donors, whether grown in FCS or in autologous serum, EBV infection generated T cells cytotoxic for the autologous LCL; the response in uninfected control cultures was markedly lower. With seronegative donor cultures grown in FCS, there was virtually no difference in the capacity of T cells generated in infected or uninfected cultures to lyse the autologous LCL. Moreover, cells from seronegative donors cultured in human serum gave no detectable lysis of autologous LCL in either infected or uninfected cultures, clearly showing the absence of a response to EBV. This evidence shows that it is possible to distinguish the generation of specific cytotoxic T cells by FCS from generation by EBV, and with certain donors the apparently EBV-induced response may actually include a significant component induced by FCS in the medium. The cytotoxicity patterns of EBV-induced and FCS-induced T cells for autologous and allogeneic LCL targets showed a degree of parallelism, stressing the need for caution in interpretation of data obtained from cultures using FCS. PMID- 6268555 TI - Isolation of two novel envelope recombinant leukemogenic viruses from Moloney leukemia virus stocks. AB - Two dual recombinant murine leukemia viruses were isolated from Moloney leukemia virus passed in France for 17 years. These new isolates share most of the biological properties of previously described HIX virus isolated from a line of Moloney virus maintained in the United States. However, they differ from the HIX virus and from other recombinant viruses by the absence of a xenotropic oligopeptide thought to have been characteristic of all xenotropic and recombinant virus envelope glycoprotein. PMID- 6268556 TI - Experimentally induced synovial sarcoma. AB - Synovial sarcoma has been induced in the knee joints of rats by intra-articular injection of 9-10-dimethyl-1-2-benzanthracene. Tumours developed from three to six months after the last injection. The neoplasms obtained were classified as synovial sarcoma (50%), fibrosarcoma (25%), giant cell sarcoma (15%), malignant fibrous histiocytoma (10%). The synovial membrane in the treated knee joints presented a chronic synovitis associated with fibrosis and proliferation of the lining cells. The primitive tumour spread locally infiltrating muscle and the adjacent bones. Metastases occurred most frequently to the lungs (70%) and liver (20%); lymph nodes were involved in 10%. PMID- 6268557 TI - The role of T3 and its receptor in efficient metabolisers receiving very-low calorie diets. AB - Obese patients taking a 1.34 MJ/day formula diet showed a steady decline in the rate of weight loss after several weeks and this was associated with a fall in RMR, serum T3 levels and the number of T3 receptors on peripheral lymphocytes. The addition of T3 (60 micrograms/day) to the dietary regime produced a significantly greater weight loss by the 12th week. Analysis of individual thyroid hormone levels revealed those patients taking the T3 tablets who achieved the greatest weight loss had the lowest serum T3 levels but the greatest suppression of serum T4 values. The serum T3 levels in the T3 treated subjects were negatively correlated with the lymphocyte rece 12th week. Analysis of individual thyroid hormone levels revealed those patients taking the T3 tablets who achieved the greatest weight loss had the lowest serum T3 levels but the greatest suppression of serum T4 values. The serum T3 levels in the T3 treated subjects were negatively correlated with the lymphocyte rece 12th week. Analysis of individual thyroid hormone levels revealed those patients taking the T3 tablets who achieved the greatest weight loss had the lowest serum T3 levels but the greatest suppression of serum T4 values. The serum T3 levels in the T3 treated subjects were negatively correlated with the lymphocyte receptor capacity. It is postulated that the fall in the number of T3 receptors is the primary event leading to the observed serum hormone level changes in the T3 treated patients. PMID- 6268558 TI - Entamoeba histolytica: localization and characterization of ca2+-dependent nucleotidases. PMID- 6268559 TI - CDC guidelines on infection control. PMID- 6268560 TI - Categories for infection control: a new approach from the Centers for Disease Control. PMID- 6268562 TI - Exploratory laparotomy in the detection of abdominal metastases of primary lung cancer. AB - From January 1974 to December 1976 122 exploratory laparotomies were performed in patients with primary lung cancer. With this method detection of asymptomatic abdominal metastases was achieved in 23.8% of the cases. The more frequent sites of metastases were the abdominal lymph nodes and the liver. The most common histological findings were oat-cell carcinoma (50%) and adenocarcinoma (35.7%). The detection of asymptomatic abdominal metastases using this procedure permitted the modification of the clinical staging (adopted by the UICC) in 9.8% of the cases, with emphasis on clinical stage I and II. This diagnostic procedure is harmless: no patient died during the period of the study. The authors recommended inclusion of exploratory laparotomy as an adequate routine means both for the detection of abdominal metastases and for the surgical and clinical staging of primary lung cancer, with emphasis on female patients and clinical stages I and II. PMID- 6268561 TI - Surgical treatment of cancer of the colon. AB - The authors give a brief review of the course of surgical treatment for colon cancer in the last two decades, as reported in the medical literature. Between 1960 and 1980 they examined 619 patients. Of these, 599 underwent surgery: 436 (72.8%) had radical surgery and 163 (27.2%) received palliative operations. The morbidity was 12.1% and the mortality 2.7%. Sixty per cent of the patients in Dukes' class "A" and "B" were alive after five years, against 28% of those in class "C" and non in class "D". The results obtained during the 1970 to 1980 period are not significantly better than those obtained from 1960 to 1969. On the basis of this experience, the authors describe their present approach for the treatment of tumors of the colon and explain in detail the preoperative preparation of the patients, the extension of the excisions and of the lymphectomies, according to the site of the cancer and its local or distant invasion, the use of temporary derivative colostomies and the application of additional medical therapies. Guidelines for reaching an early diagnosis of colon carcinoma are given, in order to improve the postoperative survival rate. PMID- 6268563 TI - Leiomyoma of Meckel's diverticulum associated with adenocarcinoma of the descending colon. AB - A case of leiomyoma of Meckel's diverticulum associated with a carcinoma of the descending colon, presenting with intestinal obstruction, is described. Only two cases of smooth muscle tumors of the small intestine associated with carcinoma of the large bowel have been described so far, and ours is probably the first case of its kind to be reported. The importance of angiography and a through intraoperative exploration is stressed. PMID- 6268564 TI - Induction of ocular herpes simplex virus shedding by iontophoresis of epinephrine into rabbit cornea. AB - Ocular herpes simplex virus type 1 (HSV-1) shedding from the latently infected rabbit was induced by iontophoresis of 0.01% epinephrine into the eye. The iontophoresis of epinephrine was at 0.8 mAmp for 8 min once a day for 3 consecutive days. Shedding was determined by the presence of HSV-1 in the tear film obtained with eye swabs. Unilateral epinephrine iontophoresis performed 60 days after inoculation of the virus resulted in ipsilateral HSV-1 shedding in all cases (7/7). Bilateral epinephrine iontophoresis performed on selected days during 170 to 365 days after inoculation resulted in HSV-1 shedding in 75% of the eyes (21/28) and 100% of the rabbits (14/14). All shedding was initiated within 3 days after the third treatment with epinephrine iontophoresis. The shedding frequency induced by epinephrine iontophoresis was significantly higher (pb less than 0.05) than that induced by the other methods employed. HSV-1 was detected in one or both cocultivated explants of trigeminal and superior cervical ganglia for every eye in all experimental groups, indicating that all eyes had the potential to shed. In conclusion, epinephrine iontophoresis induced ocular HSV-1 shedding reliably and with a high frequency in the latently infected rabbits. Furthermore, we suggest that this easily reproducible model of viral shedding offers a system for studying the factors involved in recurrent HSV-1 ocular infections. PMID- 6268565 TI - Evaluation of the parameters of the ELISA procedure for feline type C retroviral antigens: assay of FeLV antigens in chronically infected or nonproducer transformed cells. AB - The successful application of an improved enzyme-linked immunosorbent assay (ELISA) to the specific detection and quantitation of feline leukemia virus (FeLV) is presented. The methods described can detect FeLV antigens at the picogram/milliliter level using a fluorometric assay for peroxidase-linked antibody. The use of a fluorogenic substrate resulted in at least a 9-fold increase in sensitivity of the peroxidase assay. FeLV antigens could be specifically detected in chronically infected cells as well as in feline sarcoma virus-transformed nonproducer mink cells which only partially express viral proteins. PMID- 6268566 TI - Lack of association between BK virus and ependymomas, malignant tumors of pancreatic islets, osteosarcomas and other human tumors. AB - BK virus (BKV) DNA sequences were not detected in 142 human tumors analyzed by DNA-DNA reassociation kinetics and blot hybridization. The investigation was focused mainly on those rare types of human tumors (ependymomas, choroid plexus papillomas, tumors of pancreatic islets and osteosarcomas) that are induced with highest frequency by BKV in experimental animals. In addition, other tumors of the urinary apparatus and of the central nervous system were analyzed. BKV tumor (T) antigen was not detected in neoplastic tissues, and BKV T antibodies were not found in sera and cerebrospinal fluids from patients with neoplasms. Sequences homologous to BKV DNA were found in normal tissue from a kidney carrying a carcinoma. The neoplastic tissue from the same organ, however, had no sequences homologous to BKV DNA. Such DNA does not belong to BKV but probably to another papovavirus related to BKV. PMID- 6268567 TI - Structural proteins and glycoproteins of infectious bronchitis virus particles labeled during growth in chick embryo cells. AB - Seven Australian infectious bronchitis viruses incorporated radioactive amino acid label during growth in two types of cell culture. From purified virions, four major polypeptides of molecular weights 91,000 (GP91), 51,000 (VP51), 25,000 (GP25) and 23,000 (VP23) were separated by PAGE. Two minor polypeptides of molecular weights 210,000 (GP210) and 185,000 (GP185) were also identified. 3H glucosamine was incorporated during growth of virus into GP210, GP185, GP91 and GP25. Bromelain digestion of virions removed GP210, GP185 and GP91, leaving VP51, GP25 and VP23 in a large subviral particle. All seven viruses, which were of six serological subtypes, formed apparently identical polypeptide profiles. PMID- 6268568 TI - Synthesis of thymidine kinase (TK) in Epstein-Barr virus-superinfected Raji TK negative cells. AB - Epstein-Barr virus (EBV) from P3HR-1 cells, but not from B95-8 cells, can induce the synthesis of thymidine kinase (TK) in TK-negative Raji cells. The synthesis of TK was slightly reduced, but not inhibited, when cells were cultivated in the presence of cytosine arabinoside (ara-C). On the other hand, the synthesis of TK in ordinary Raji cells was enhanced in the presence of the drug. Thymidine-beta-D arabinofuranoside (ara-T) was capable of reducing the conversion rate of thymidine to TdR nucleotides by extracts prepared from superinfected Raji TK cells, but had no influence on TK activity in cell extracts from ordinary Raji cells and EBV-negative Ramos cells. This suggested a broader substrate specificity of the virally induced enzyme. PMID- 6268569 TI - Persistent infection of human lymphoid cells with poliovirus and development of temperature-sensitive mutants. AB - Exposure of several spontaneously transformed human lymphoid cell lines to attenuated and virulent types 1 and 2 poliovirus strains led to an initial sharp increase in virus titer followed by a persistent infection. Virus was present as late as 80 passages after infection. The morphology, cell count and viability of virus- and mock-infected cells were similar. Approximately 1% of the cells scored as infectious centers, and the cultures could be cured by specific antiserum. Virus produced during persistent infections initiated with a virus that readily forms plaques at 40 degrees, Mahoney virus, showed an increase in temperature sensitivity and a decrease in plaque size. PMID- 6268570 TI - Determination of adenosine kinase activity by high-pressure liquid chromatography. AB - High-pressure liquid chromatography (reverse-phase mode) was used to assay adenosine kinase in cell and tissue extracts. The method is optimized for a rapid and selective analysis using 6-methylthiopurine riboside as substrate, isocratic elution and detection at 300 nm. A complete separation of substrate and product is achieved in about 3 min with no interference by other UV-absorbing compounds; the limit of detection is 20 pmoles. PMID- 6268571 TI - [Leukocytoclastic vasculitis due to drug allergy presenting as generalized pustular exanthema]. AB - A 68-year-old man who was treated for febrile angina with gentamicin, doxycycline, phenoxymethylpenicillin K, and minocycline developed a generalized pustular exanthema favoring the predilected areas (hands, feet). Apart from a subepidermal pustule, the most noteworthy histological finding was a pronounced leukocytoclastic vasculitis. After disappearance of the skin lesions an intradermal test using cilligen (penicilloyl-polylysin) was conducted. The test gave a strongly positive early reaction, and 48 h after this an acute pustular outbreak developed analogous to the original manifestation. Doxycycline tested late, produced no exacerbation even though it was positive in the intradermal test. This pustular allergical drug rash can be classified as a vasculitis leucocytoclastica allergica which, as we know, appears in various clinical forms. It does not form a new disease entity. Terms used so far, such as "pustular necrotizing angiitis", "generalized pustular drug rash", "acute generalized pustular bacterid", "pustulosis acuta generalisata", only partially correspond to the actual pathoetiology. PMID- 6268572 TI - Electret--a new tool for measuring concentrations of radon and thoron in air. PMID- 6268573 TI - The diagnosis of hereditary fructose intolerance. AB - Hereditary fructose intolerance (HFI) is a potentially life-threatening disorder and can be suspected from a detailed nutritional history. The usefulness of 2 diagnostic procedures, fructose tolerance test (FTT) and aldolase assay on biopsied liver, was studied. A standardized intravenous FTT with 200 mg/kg b.w. was done on 11 children with HFI, 17 age-matched contrast children, 6 adults with HFI and 6 adult controls. Blood glucose, phosphorus, urate, magnesium and fructose were followed for 2 hours. By the FTT, each HFI individual was reliably distinguished from controls and contrasts and even from those with acute liver disease other than HFI. Both children with non-HFI hepatopathy examined by both procedures had a normal FTT in spite of reduced liver fructaldolase activity. HFI children responded to the FTT by earlier and more pronounced hypoglycemia than adults, and one girl converted to an adult type response between the ages 12 and 181/2 years. Responses of two HFI sibling pairs and of one set of monozygotic twins were typical for age, but resemblance was no greater than within the unrelated HFI probands. The intravenous FTT is judged a reliable diagnostic tool, simple and harmless if done in hospital. Essential fructosuria is readily diagnosed by the FTT, but fructose-1,6-diphosphatase deficiency and HFI are not differentiated with certainty. Liver biopsies were obtained from 35 children with HFI, 14 contrast persons and 10 controls (of which 9 organ donors) and examined enzymatically. Deficiency of fructaldolase was observed in all HFI children but also in some contrast children suffering from acute liver disease other than HFI. In these, HFI could only be excluded when the reduced activity of reference enzymes such as fructose-1,6-diphosphatase and glucose-6-phosphatase and liver histology were included in the evaluation. In one deceased HFI infant, fructaldolase was deficient in both, liver and kidney cortex. Extent of antibody activation and of heat inactivation of residual fructaldolase varied between unrelated HFI patients but not within families. These results did not contribute to diagnosis but further documented genetic heterogeneity of HFI. For diagnosis of HFI we recommend 1. immediate elimination of fructose from the diet, 2. the intravenous FTT after several weeks of fructose withdrawal, and 3., should diagnosis still be uncertain, laparoscopic liver biopsy for assay of fructaldose and of reference enzymes and for histology. PMID- 6268574 TI - Cystic partially differentiated nephroblastoma. AB - The clinical and pathologic findings of a case of cystic partially differentiated nephroblastoma in a 5-month-old boy is reported. We believe that it probably represents the differentiated counterpart of nephroblastoma. After nephrectomy, the child was given a short course single cytotoxic therapy with vincristine for 6 months. PMID- 6268575 TI - Radiation therapy in the treatment of malignant fibrous histiocytoma. PMID- 6268577 TI - Keeping students successful: an interdisciplinary approach. PMID- 6268576 TI - Dosimetry of 131I-labeled anti-ferritin in hepatoma: a model for radioimmunoglobulin dosimetry. PMID- 6268579 TI - On promoting creativity. PMID- 6268578 TI - Educational cooperation among nursing, medicine and pharmacy: a success story. PMID- 6268580 TI - Clinical components in graduate programs in nursing. PMID- 6268581 TI - Concurrent validity of ACT-PEP and NLN achievement tests: a pilot study. PMID- 6268582 TI - Liaison nurse: what is the role? PMID- 6268583 TI - Educational problems in a woman's profession. PMID- 6268584 TI - Effect of bovine viral diarrhea virus on conception in cattle. AB - Sixty adult dairy cows were used to study the effect of bovine viral diarrhea (BVD) virus on conception when inoculated with the virus within 2 hours after breeding. Fifteen cows were assigned at random to each of 4 groups. Group I (control) cows were given 3 ml of diluent in the uterus; group II (seropositive) cows were given 3 ml of BVD virus in the uterus; group III (seronegative) cows were given 3 ml of BVD virus in the uterus; and group IV (seronegative) cows were given 3 ml of BVD virus orally and 3 ml intranasally. At 35 days after breeding, the cows were slaughtered, their reproductive tracts were recovered, and pregnancy rates were recorded. The pregnancy rates for groups I, II, III, and IV were 67%, 60%, 27%, and 67%, respectively. The group III pregnancy rate was significantly lower (P less than 0.05) than that for the control group. However, the similarity of rates for groups I, II, and IV indicates that BVD virus does not inhibit conception when cattle are infected by natural routes or when virus is infused into the uterus of seropositive cows at the time of breeding. These results indicate that BVD virus is not a major cause of repeat breedings in cattle. PMID- 6268585 TI - Canine Silica Urolithiasis. AB - Silica "jack-stone" uroliths developed in the urinary bladder and urethra of 83 dogs living in the United States. Naturally occurring silica jack stones have not been encountered prior to 1976. German Shepherd Dogs comprised more than 1/3 of affected animals; the remainder encompassed 26 other breeds. In this series, 81 were males and 2 were females. The mean age of the dogs was 5.8 years, with a range of 1.5 to 12 years. Several observations prompt the hypothesis that development of silica uroliths may be related to diet. Although most silica uroliths had a characteristic jack-stone appearance, not all silica uroliths had a jack-stone configuration and not all jack stones were composed of silica. Some calculi were comprised of a combination of silica and struvite. Silica uroliths were radiodense, compared with adjacent tissue, but were not associated with identifiable crystals in urine. The urine pH of affected dogs varied from acid to alkaline. Silica urolithiasis recurred in 5 dogs following surgery. Urinary tract infections, when they occurred, appeared to be a sequela of silica urolithiasis. Pending further studies, management of silica uroliths should include their removal from the urinary tract and eradication of associated urinary tract infections. Prophylactic measures should include attempts to augment urine volume and change of diet. PMID- 6268586 TI - Effect of functional adrenocortical tumors on plasma cortisol and corticotropin concentrations in dogs. AB - Plasma endogenous adrenocorticotropic hormone (ACTH) concentrations as well as basal and post-ACTH-stimulation plasma cortisol concentrations were measured in 6 dogs ultimately shown to have hyperfunctioning adrenocortical tumors. The basal and post-ACTH-stimulation plasma cortisol concentrations were found to fluctuate in 4 dogs in which repeat studies were done. Three dogs had at least 1 normal and 1 abnormally high plasma cortisol concentration after exogenous ACTH administration. A 4th dog had 1 normal and 1 abnormally high resting cortisol concentration. One dog tested twice 3 days apart had similar test results each time and a 6th dog was tested once. All of the dots had at least 1 plasma endogenous ACTH concentration greater than 2 standard deviations below the normal mean. All endogenous ACTH concentrations were less than those previously reported for dogs with pituitary-dependent hyperadrenocorticism. The results indicated that the diagnosis of adrenocortical tumor cannot reliably be made on the basis of the plasma cortisol response to exogenous ACTH; however, the use of plasma endogenous ACTH determination can be an important diagnostic aid. PMID- 6268587 TI - Electron microscopic studies on localization of phosphatases in the laying hen parathyroid. AB - Localization of phosphatases in the parathyroid of laying hens was examined by electron microscopy. Activities of both alkaline phosphatase and adenosine triphosphatase were intensive on the apposed plasma membranes between contiguous chief cells, but weak or almost lacking on those facing the interstitial connective tissue, and this finding differed from previous data in mammals. This difference seemed to be associated with the fact that in the parenchymal cells of the hens there was found a narrow, delicate filament-rich zone in the peripheral cytoplasm along the basal lamina. Activities of both thiamine pyrophosphatase and inosine diphosphatase were seen in most of the Golgi cisternae having serpentine tubular profiles, and this indicated that the latter cisterna belong to the Golgi apparatus. Acid phosphatase activities were mainly demonstrated in lysosomal dense bodies, including autophagic vacuoles, as well as in most of the lipofuscin granules, and only occasionally encountered in the Golgi apparatus, including the thick membranous cisternae, in contrast with findings in mammals. The reason for this weak activity in this organelle was discussed in relation to calcium metabolism, secretory products, and lysosomes in the laying hen. PMID- 6268588 TI - The X-ray structural investigation of 6-(n,n-1,6-hexyleneformamidine) penicillanic acid (mecillinam). AB - A new type of 6-formamidinepenicillanic acid in which the omega-nitrogen atom is involved in the azaheptane ring (mecillinam) having a strong selective activity against Gram-negative bacteria strains has been investigated by the X-ray single crystal diffraction methods using crystals in the solvated state. The conformation of penam part as well as of the amidine group is discussed. Two independent molecules of mecillinam found in the asymmetric unit of the crystal cell differ from each other in their detailed conformations. The problem of the stability of the compound has been discussed also. PMID- 6268589 TI - Separation and biologic activities of individual components of S15-1, a streptothricin class antibiotic. AB - A method is described for isolation of gram quantities of the components of the streptothricin complex S15-1 utilizing CM Sephadex column chromatography eluted with 10% acetic acid as an eluant followed by gradient elution with 10% acetic acid containing 0.02 N approximately 0.03 N HCI. Streptothricins F and E, as well as an unidentified component C1, have been isolated and their comparative biological activities determined. Streptothricins F and E were comparable in taeniacidal activity in mice infected with Hymenolepis nana ia feeding either one at 0.05% in the diet removed 92 approximately 100% of the adult tapeworms. The unidentified component C1 was inactive at the levels tested. In contrast, component C1 was the most active in antimicrobial activity against Bacillus subtilis and in inhibiting the urease activity of proteus mirabilis. In the former test, the ratios of activity were; 1:7:30 for F:E:C1 and in the latter; 1:2:4 for F:E:C1. PMID- 6268590 TI - Selective antiviral activity of the antibiotic 2'-amino-2'-deoxyribofuranosyl adenine. AB - The effect of new anti-mycoplasmal antibiotic, 2'-amino-2-deoxy-9-beta-D ribofuranosyl adenine (2-AA) on virus multiplication was investigated. The 2-AA inhibited only the multiplication of measles virus among the viruses tested; i.e., herpes simplex virus, BK virus, vesicular stomatitis virus, measles virus and Echo virus. At a concentration of 5 micrograms/ml of 2-AA, the inhibition of measles virus replication was complete, i.e., no infectious virus nor viral antigen detected. In contrast, 9-beta-D-arabinofuranosyl adenine (50 micrograms/ml) was active to herpes simplex virus and BK virus, and was inactive to measles virus, vesicular stomatitis virus and Echo virus. Results described herein may suggest that 2-AA affects the late function (perhaps the translation step) of the replication of measles virus. PMID- 6268591 TI - Characterization of chromosomal and membrane associated plasmid in Bacillus brevis ATCC 9999. AB - A covalently closed circular (ccc) DNA, with a weight of 44.7 x 10(6) daltons, has been isolated from Bacillus brevis ATCC 999 (a gramicidin S producer) and from the gramicidin S-negative mutant EB16. The ccc DNA in the case of the parent strain, is mainly (99%) attached to the chromosome and membrane fraction. A restriction enzyme map of the plasmid DNA was constructed for the enzymes SalI, SmaI and BamHI, which cleaved the plasmid DNA into two, two and six fragments respectively. Further digestion with the endonucleases EcoRI and HindIII cleaved the plasmid into 17 and 22 fragments. PMID- 6268592 TI - Ro 13-9904: affinity for penicillin binding proteins and effect on cell wall synthesis. PMID- 6268593 TI - Effect of combination of cefsulodin and mecillinam. AB - The effect of cefsulodin in combination with mecillinam was examined against a wide range of bacterial species. The antibacterial spectrum was widened by the combination of cefsulodin and mecillinam in the ratio of 5:1 and 10:1. In overall observations, in the in vitro test, a synergistic effect against clinical isolates was found on Klebsiella pneumoniae, Citrobacter freundii, Enterobacter cloacae, Serratia marcescens, proteus mirabilis and Proteus vulgaris, and an additive effect was found on Staphylococcus aureus, Escherichia coli, Proteus morganii, Proteus rettgeri, Proteus inconstans and Pseudomonas aeruginosa. In in vivo tests, a synergistic effect was observed on S. marcescens TN 66 and K. pneumoniae DT infections and an additive effect was observed on S. aureus 308 A 1, E. coli O-111 and T-7, C. freundii TN 518, E. cloacae TN 603, P. vulgaris GN 4712, P. morganii Tn 373 and P. aeruginosa U 31 infections. PMID- 6268594 TI - Synergistic effect of cephalexin with mecillinam. AB - In vitro and in vivo synergistic effects of cephalexin and mecillinam against Escherichia coli, Klebsiella pneumoniae, Enterobacter sp., Serratia marcescens and Proteus sp. were demonstrated and their action mechanism were also discussed. The growth curve after the exposure of cephalexin and mecillinam at the concentrations at which these antibiotics had no effects when given alone showed a decreased of the turbidity and the presence of a bactericidal effect. In experimental infection in mice, the combination of both drugs showed a synergistic effect and excellent therapeutic effect. The blood concentration ratio of cephalexin to mecillinam was coincident with the concentration ratio of these antibiotics at which the synergistic effect was observed in vitro. Phase contrast and scanning electron somewhat elongated bacteria and formation of spindle cells with swelling in the central part. A leakage of the cellular contents from part of the swelled cell wall was observed by transmission electron microscope. Cephalexin showed an affinity for penicillin binding proteins (PBPs) 1a and 3 in Escherichia coli and mecillinam showed an affinity for PBP-2. When these antibiotics were used concurrently, they exerted an additive effect to increase the affinity for PBPs. The lytic activity was increased much more after the combination of two antibiotics than after a single exposure. PMID- 6268595 TI - Ribosomal proteins S9 and L6 participate in the binding of [3H]dibekacin to E. coli ribosomes. AB - The degrees of binding of [3H]dibekacin to LiCl-treated cores of E. coli ribosomes were reduced by increasing LiCl concentrations. The 1.15 M LiCl core lost 70 approximately 80% of the original binding capacity. The antibiotic attachment to the 1.15 M LiCl core was restored by reconstitution with the split proteins (SP), which were obtained by the treatment of 70S ribosomes with LiCl at concentrations of 0.8 approximately 1.15 M. The basic proteins, split off during the transition from 0.4 M LiCl core to 0.8 approximately 1.15 M LiCl core, seemed to be involved in the drug binding. SP0.4 approximately 1.15, which was obtained by the treatment of the 0.4 M LiCl core with 1.15 M LiCl, was fractionated by CM Sephadex C-25 column chromatography, and each fraction was assayed for protein composition and the capability of restoring the ability of the 1.15 M LiCl core to bind the drug. Of ribosomal proteins eliminated with 1.15 M LiCl, the addition of either S9 or L6 alone to the 1.15 M LiCl core was observed to restore approximately 50% of the binding as compared to the 70S ribosome alone, and both proteins restored about 70% of the binding. The results suggested that ribosomal proteins S9 and L6 were involved in the attachment of [3H]dibekacin to the ribosome. The antibiotic binding to the 70S ribosome and 1.15 M LiCl core reconstituted with S9 and L6 was considerably inhibited by unlabelled dibekacin or kanamycin, and partially inhibited by gentamicin or neomycin, but was not significantly affected by streptomycin or viomycin. PMID- 6268596 TI - The effect of erythrosine on the surface-associated bacteria of the rat stomach and caecum. PMID- 6268597 TI - Plasmid-mediated partial cross-resistance between ampicillin, mecillinam and cefamandole in Salmonella johannesburg and Salmonella typhimurium. PMID- 6268598 TI - Synergistic activity of cefoperazone in combination with beta-lactamase inhibitors. PMID- 6268599 TI - Comparative activity of mecillinam and ampicillin singly and in combination in the urinary bladder model and experimental mouse model. PMID- 6268600 TI - Inhibitory effect of adenosine 3',5'-phosphate on cell division of Escherichia coli K-12 mutant derivatives. AB - Cell division of Escherichia coli K-12 strain PA3092 was inhibited by the addition of adenosine 3',5'-phosphate (cAMP), and the cellular morphology was changed from rods into filaments. Nucleoids in the filaments were regularly distributed and septum formation was perfectly inhibited. This inhibition of cell division by cAMP was reversed by the addition of guanosine 3',5'-monophosphate. To examine whether the inhibitory effect of cAMP on cell division in E. coli PA3092 was specific, its effect in several parental strains was investigated. Induction of cell filamentation by cAMP was observed in E. coli PA309 and P678, but not in E. coli W505, W1, Y10, or the wild-type strain. This result suggests that filamentation by cAMP in E. coli PA3092, PA309, and P678 was due to the mutagenesis by which E. coli P678 was derived from E. coli W595. PMID- 6268601 TI - Translocatable resistance to mercuric and phenylmercuric ions in soil bacteria. AB - Of a sample of 42 gram-negative Hg-resistant bacteria, three (a Pseudomonas fluorescens, a Klebsiella sp. and a Citrobacter sp.) contained translocatable elements conferring resistance to Hg2+ (all three) and to Hg2+ and phenylmercuric acetate (P. fluorescens). The discovery of transposable phenylmercuric acetate resistance extends the range of known resistance "transposons" from heavy metals and antibiotics to organometallic compounds. PMID- 6268602 TI - The tsx protein of Escherichia coli can act as a pore for amino acids. AB - The tsx protein is known to be a specific diffusion pathway for nucleosides. The ability of this protein to facilitate the transport of molecules other than nucleosides was examined in strains lacking detectable amounts of porin (ompB mutants). The tsx protein was shown to promote serine, glycine, and phenylalanine transport and to have no effect on either glucose or arginine transport. PMID- 6268603 TI - Biosynthesis of bacterial glycogen: activator specificity of the adenosine diphosphate glucose pyrophosphorylases from the genus Rhodospirillum. AB - The adenosine diphosphate (ADP) glucose pyrophosphorylases from Rhodospirillum fulvum, Rhodospirillum molischianum, and Rhodospirillum tenue were partially purified, and their kinetic properties were studied. The enzyme from the three organisms was found to be activated by pyruvate and thus was similar to the Rhodospirillum rubrum enzyme that had been previously studied (C. E. Furlong, and J. Preiss, J. Biol. Chem. 244:2539-2548, 1979). The enzymes from R. fulvum, R. molischianum, and R. tenue were also activated by oxamate, an analog of pyruvate. Other alpha-keto acids, alpha-ketobutyrate and hydroxypyruvate, activated to a smaller extent. The presence of pyruvate increased the apparent affinity for adenosine 5'-triphosphate and MgCl2 for all three enzymes. The R. molischianum enzyme has very little sensitivity to inhibition by adenosine 5'-monophosphate, ADP, or inorganic phosphate. However, R. tenue ADPglucose pyrophosphorylase is very sensitive to inhibition by adenosine 5'-monophosphate, and the R. fulvum enzyme is inhibited by ADP. Increasing pyruvate concentration reversed the inhibition caused by adenosine 5'-monophosphate or ADP. Since ADPglucose is the glycosyl donor for synthesis of glycogen, it is possible that in vivo glycogen synthesis is regulated by the concentration of pyruvate and, in the case of R. fulvum and R. tenue, by the ratio of pyruvate concentration to inhibitor concentration. PMID- 6268605 TI - Mitochondrial biogenesis during fungal spore germination: respiration and cytochrome c oxidase in Neurospora crassa. AB - The germination of conidiospores of wild-type Neurospora crassa was found to be dependent upon the function of the cytochrome-mediated electron transport pathway. The cyanide-insensitive alternate oxidase did not contribute significantly to the respiration of these germinating spores. The dormant spores contained all of the cytochrome components and a catalytically active cytochrome c oxidase required for the activity of the standard respiratory pathway, and these preserved components were responsible for the accelerating rates of oxygen uptake which began immediately upon suspension of the spores in an incubation medium. Mitochondria of the dormant spores contained all of the subunit peptides of the functional cytochrome c oxidase; nevertheless, de novo synthesis of these subunits began at low rates in the first stages of germination. Reactivation of the respiratory system of germinating N. crassa spores seems not to be dependent initially upon the function of either the mitochondrial or cytoplasmic protein synthesizing systems. The respiratory activity of spores of three mutant cytochrome c oxidase-deficient strains of N. crassa also was found to depend upon the function of the cytochrome electron transport pathway; the dormant and germinating spores of these strains contained a catalytically active cytochrome c oxidase. Cytochrome c oxidase may be present in the dormant and germinating spores of these strains as the result of a developmental-phase-specific synthesis of and requirement for the enzyme. PMID- 6268604 TI - Complementation of replication-deficient deletion derivatives of plasmid mini-F. AB - Deleted mini-F plasmids with defects in replication were constructed and tested to see whether they could be rescued through complementation by a helper plasmid. This allowed us to identify two genetic loci determining trans-acting functions required for stable maintenance of plasmid mini-F, one encoded by the PstI fragment from 45.7 to 47.3 F-coordinates (F) and the other most probably located in the region from 43.1 to 43.8 F. The smallest mini-F plasmid that could be established through complementation consists of the PstI fragment 44.0 to 45.7 F, encoding origin II and the incB locus. PMID- 6268606 TI - Genetic characterization of aggregation-defective developmental mutants of Myxococcus xanthus. AB - The transposon Tn5 was used to map temperature-sensitive mutants of Myxococcus xanthus defective in aggregation (C. E. Morrison and D. R. Zusman, J. Bacteriol. 140:1036-1042, 1979). Seven of the eight mutants showing a similar terminal phenotype (rough) were found to be tightly linked. These mapped in a group of loci which we have designated aggR1, aggR2, aggR3, and aggR4. Temperature sensitive mutants having a different terminal phenotype were not liked to aggR. A search through a group of nonconditional rough mutants indicated that a much lower proportion of these (1 of 35) mapped in aggR. Thus, aggR is probably only one of many sites which can lead to the rough phenotype when mutated. Localized mutagenesis was used to isolate nine additional aggR mutants. All mapped within aggR1, aggR2, or aggR3, and none was found outside this region. Thus, we have characterized a cluster of developmental genes which are needed for aggregation in M. xanthus. The localization of a Tn5 insert adjacent to this region makes possible further manipulation of these genes. PMID- 6268607 TI - Cloning of the genes for penicillinase, penP and penI, of Bacillus licheniformis in some vector plasmids and their expression in Escherichia coli, Bacillus subtilis, and Bacillus licheniformis. AB - By using plasmid pMB9, penicillinase genes (penP and penI) from both the wild type and constitutive strains of Bacillus licheniformis 9945A were cloned in EScherichia coli. When a low-copy-number plasmid was used, both wild-type and constitutive penicillinase genes could be transferred into Bacillus subtilis. However, when a high-copy-number plasmid was used, only the genes of the wild type could be transferred. These recombinant plasmids in B. subtilis could all be transferred by the protoplast transformation procedure into B. licheniformis. Transformants of E. coli were resistant to ampicillin (20 micrograms/ml) in spite of the low penicillinase activities (7 U/mg of cells). However, transformants of B. subtilis and B. licheniformis were sensitive to ampicillin (20 micrograms/ml) even in high penicillinase activities (more than 10,000 U/mg of cells). The secretion of penicillinase was rarely observed in E. coli. In contrast, penicillinases secreted from transformants of B. subtilis and B. licheniformis were around 30 and 60% of the total activities, respectively. We took advantage of the plasmids to permit the construction of hetero- and mero-polyploid structures in host cells, and we discuss a regulatory mechanism of penicillinase synthesis in B. licheniformis. PMID- 6268608 TI - Nucleotide sequence of the structural gene for tryptophanase of Escherichia coli K-12. AB - The tryptophanase structural gene, tnaA, of Escherichia coli K-12 was cloned and sequenced. The size, amino acid composition, and sequence of the protein predicted from the nucleotide sequence agree with protein structure data previously acquired by others for the tryptophanase of E. coli B. Physiological data indicated that the region controlling expression of tnaA was present in the cloned segment. Sequence data suggested that a second structural gene of unknown function was located distal to tnaA and may be in the same operon. The pattern of codon usage in tnaA was intermediate between codon usage in four of the ribosomal protein structural genes and the structural genes for three of the tryptophan biosynthetic proteins. PMID- 6268609 TI - Interconversion of components of the bacterial proton motive force by electrogenic potassium transport. AB - The influence of K+ ions on the components of the transmembrane proton motive force (delta mu H+) in intact bacteria was investigated. In K+-depleted cells of the glycolytic bacterium STreptococcus faecalis the addition of K+ ions caused a depolarization of the membrane by about 60 mV. However, since the depolarization was compensated for by an increase in the transmembrane pH gradient (delta pH), the total proton motive force remained almost constant at about 120 mV. Half maximal changes in the potential were observed at K+ concentrations at which the cells accumulated K+ ions extensively. In EDTA-treated, K+-depleted cells of Escherichia coli K-12, the addition of K+ ions to the medium caused similar, although smaller changes in the components of delta mu H+. Experiments with various E. coli K-12 K+ transport mutants showed that for the observed potential changes the cells required either a functional TrkA or Kdp K+ transport system. These data are interpreted to mean that the inward movement of K+ ions via each of these bacterial transport systems is electrogenic. Consequently, it leads to a depolarization of the membrane, which in its turn allows the cell to pump more protons into the medium. PMID- 6268610 TI - Spontaneous mutators of salmonella typhimurium LT2 generated by insertion of transposable elements. AB - Spontaneous mutators of Salmonella typhimurium LT2 were generated by inserting the transposable element Tn5 or Tn10 into the bacterial chromosome. Two mutators mapped at the position of the mutH and mutL loci of S. typhimurium, and two other mutators mapped at positions corresponding to the mutS and uvrD loci of Escherichia coli. A fifth mutator, mutB, did not map at a position corresponding to any of the known mutators of S. typhimurium or E. coli. The mutH,L,S and uvrD alleles increased the frequency of both spontaneous base substitution and frameshift mutations, whereas the mutB allele increased the frequency only of spontaneous base substitution mutations. The increased frequency of base substitution mutations was recA+ independent in the mutH, mutL, and uvrD strains and partially recA+ independent in the mutS strain. The uvrD mutation decreased the resistance of the cells to killing by ultraviolet irradiation. The mutH,L,S and uvrD strains showed an increased sensitivity to mutagenesis by the alkylating agents methyl methane sulfonate and ethyl methane sulfonate, but not to mutagenesis by 4-nitroquinoline-1-oxide. PMID- 6268611 TI - Tetracycline resistance transposon Tn1721: recA-dependent gene amplification and expression of tetracycline resistance. AB - The 7.1-megadalton transposon Tn1721 codes for inducible tetracycline resistance (Tcr). The transposable element consists of a "minor transposon" (3.6 megadaltons) encoding functions required for transposition and a "tet region" (3.5 megadaltons) encoding resistance. Multiple tandem repeats of the tet region can be generated by recA-dependent gene amplification. This feature of Tn1721 has been used to analyze the relationship between gene dosage and Tcr. Derivatives of plasmid R388:Tn1721 containing from one to nine copies of the tet region were isolated and separately transformed into recA host cells, where they are stably maintained. The results of the study of Tcr in these strains were as follows: (i) the uninduced, "basal" level of Tcr was linearly related to gene dosage between 4 and 36 copies of tet per chromosome equivalent; (ii) the underlying mechanism could not be attributed to reduced accumulation of the drug; and (iii) induction with tetracycline elicited a four- to fivefold reduction in drug accumulation, independent of the gene dosage. PMID- 6268612 TI - Escherichia coli gal operon proteins made after prophage lambda induction. AB - Expression of the EScherichia coli gal operon under the control of the prophage lambda promoter pL leads to gross discoordinacy of gal expression. Expression of the most promoter-distal cistron galK is much greater than expression of the promoter-proximal cistron galE. We had previously shown that transcription of the gal operon is coordinate after prophage induction. A survey of protein synthesized after prophage induction indicated that lack of expression of galE is due to a failure of translation of the galE sequence in the pL-gal transcript. This failure of translation of the galE sequence may be due to extensive dyad symmetry present in the vicinity of the gal promoter region of the pL-gal transcript. This symmetry could result in a ribonucleic acid stem-loop structure, blocking the attachment of ribosomes at the Shine-Dalgarno sequence of galE. To test this model, strains bearing the IS1 or IS2 insertion, deletion, or new promoter mutation within the symmetrical region were constructed. The restoration of some galE expression after such disruptions of the symmetrical region indicated that the ribonucleic acid stem-loop structure did play a role in the discoordinate expression of gal from pL. However, failure to obtain galE expression coordinated with high levels of galK expression suggested that other components were involved, perhaps other symmetries between galE and the pL transcript. PMID- 6268613 TI - Analysis of mini-F plasmid replication by transposition mutagenesis. AB - Derivatives of a mini-F plasmid in which Tn3 is inserted in F deoxyribonucleic acid were obtained, and the sites of insertion for 40 of the derivatives were mapped. Tn3 was found to insert at many sites within mini-F, but most insertions were within the 43.0- to 43.7-kilobase (kb), 44.2- to 44.7-kb, and 45.9- to 46.3 kb segments. Hence, these segments are unnecessary for mini-F replication. Most of the Tn3 derivatives were similar to their parent miniplasmid with respect to copy number, stability, and incompatibility. Insertions at 45.15 kb and near 46.0 kb caused a moderate disruption of copy number control, and insertion at 47.6 kb resulted in unstable maintenance. Deletion derivatives lacking deoxyribonucleic acid between 40.3 and 44.76 kb and between 45.92 and 49.4 kb were obtained. This observation suggests either that mini-F contains a third origin, in addition to those already reported to be at 42.6 and 44.4 kb, or that the reported position of the secondary origin, 44.4 kb, is incorrect and that this origin is between 44.76 and 45.92 kb. PMID- 6268614 TI - Tn10 insertions in the pfkB region of Escherichia coli. AB - The locus pfkB is known to determine expression of a minor phosphofructokinase (Pfk-2). Pfk-2 and pfkB seem to be dispensable, since Tn10 insertions in pfkB, as well as deletions from Tn10 nearby, are obtainable. Strains deleted for both pfkA and pgkB are unable to grow at all on sugars whose primary route of metabolism is via fructose 6-phosphate, confirming earlier reports implicating the low Pfk-2 activity, rather than the pentose-phosphate pathway, as needed for the slow growth on sugars of pfkA pfkB+ strains. The pfkB locus probably contains the structural gene for Pfk-2, since a mutation closely linked to pfkB1, which affects growth on glycerol, is found to alter the enzyme. Partial phenotypic suppression of the pfkA mutant phenotype results from Tn10 insertion very close to the pps gene, ca. 0.5 min from pgkB. The insertion does not clearly affect either Pfk-2 or phosphoenolpyruvate synthetase, and the mechanism of suppression is unclear. PMID- 6268615 TI - Selection and characterization of ColE1 plasmid mutants that exhibit altered stability and replication. AB - This report describes a method for isolating mutants of plasmid ColE1 that exhibit unstable maintenance and altered replication characteristics. It also describes the initial characterization of four mutants isolated by that method. A chimeric plasmid, pHSG124, containing a ColE1 derivative and a temperature sensitive replication derivative of pSC101 was mutagenized in vitro, using hydroxylamine. By adjusting the growth conditions of transformants containing the mutagenized chimeric deoxyribonucleic acid, it was possible to rapidly screen colonies and identify those that had a high probability of carrying ColE1 mutants that exhibit unstable maintenance. Of those mutants, some exhibited altered copy number or accumulated catenated structures. Evidence is presented which suggests that the mutations in three of the mutants are probably located in the HaeII A fragment of ColE1. PMID- 6268616 TI - Phosphorylation of calf thymus H1 histone by muscle glycogen phosphorylase kinase. AB - Muscle glycogen phosphorylase kinase [EC 2.7.1.38] has the ability to phosphorylate five fractions of calf thymus histone. H1 histone is the most preferable substrate, and maximally about 1.3 mol of phosphate is incorporated into every mole of this histone. This reaction absolutely depends on CA2+, and the molecular activity is about one third of that of cyclic AMP-dependent protein kinase (protein kinase A). The affinity of phosphorylase kinase for H1 histone is higher than that of protein kinase A. Calmodulin stimulates this histone phosphorylation. Analysis of the N-bromosuccinimide-bisected fragments of fully phosphorylated H1 histone has revealed that the enzyme phosphorylates mostly seryl residues in both amino- and carboxyl-terminal portions, although phosphorylation of the carboxyl-terminal portion is twice as much as that of the amino-terminal portion. Fingerprint analysis indicates that the phosphorylation sites in H1 histone for this enzyme are different from the sites phosphorylated by protein kinase A. This catalytic activity also differs from that of a newly found multifunctional protein kinase which may be activated by the simultaneous presence of Ca2+ and phospholipid. PMID- 6268617 TI - Occurrence of ribitol-containing lipoteichoic acid in Staphylococcus aureus H and its glycosylation. AB - A ribitol-containing lipoteichoic acid was obtained from the 20,000 x g supernatant fraction of Staphylococcus aureus H by extraction with Triton X-100 followed by fractionation on Sepharose 6B and DEAE-cellulose columns. The purified lipoteichoic acid was composed of phosphate, glycerol, glucose, glucosamine, ribitol, and fatty acids in a molar ratio of 1 : 0.9 : 0.06 : 0.03 : 0.09 : 0.07. Based on the structural analysis of fragments from alkali and HF hydrolysis, the lipoteichoic acid appears to consist of three moieties, namely a ribitol phosphate oligomer, poly(glycerol phosphate) which has about 30 glycerol phosphate units, and beta-glucosyl-beta-glucosyl(1 leads to 1)diacylglycerol. N Acetylglucosamine was linked to the ribitol residues. The lipoteichoic acid serves as an acceptor of glycosyl moieties from UDP-glucose and UDP-N acetylglucosamine in the enzyme reaction catalyzed by the membrane preparation. The rate of enzymatic glycosylation was increased by prior treatment of the lipoteichoic acid with N-acetyl-beta-D-glucosaminidase. The glycosylation seems to occur at the ribitol residues of the lipoteichoic acid. PMID- 6268618 TI - Melting from both ends of an A-band in a myofibril. Observation with a phase contrast microscope. AB - Observation with a phase-contrast microscope clearly shows that melting of an A band, i.e., a bundle of thick (myosin) filaments, in a rabbit skeletal myofibril occurs from both ends in the pressure of high concentrations of KCl and PPi. Thick filaments partially melted from both ends can be obtained in a myofibril. PMID- 6268619 TI - The structure of cytochrome c3 from Desulfovibrio vulgaris Miyazaki at 2.5 A resolution. AB - The structure of tetraheme cytochrome c3 isolated from Desulfovibrio vulgaris Miyazaki has been determined at 2.5 A resolution by an X-ray diffraction method. Protein phases were computed by the multiple isomorphous replacement method using the native and four heavy atom derivatives, anomalous scattering measurements of the latter being considered. The mean figure of merit was 0.77. Four heme groups are exposed on the surface of the molecule. There are some short helical segments in the polypeptide chain, and hair-pin turns are often observed at glycine and alanine residues. PMID- 6268620 TI - The nucleotide sequence of 5S ribosomal RNA from Schizosaccharomyces pombe. AB - The nucleotide sequence of 5S rRNA from the fission yeast, S. pombe, has been established by post labeling procedures combined with cataloging RNase T1- and A oligonucleotides derived from unlabeled 5S rRNA. The sequence consists of 119 nucleotides without a modified base and shows more dissimilarities (at 38 positions) from that of S. cerevisiae than from that of humans (at 33 positions). PMID- 6268621 TI - Modulation of Leydig cell androgen biosynthesis and cytochrome P-450 levels during estrogen treatment and human chorionic gonadotropin-induced desensitization. PMID- 6268622 TI - Evidence for distinct subcellular sites of opiate receptors. Demonstration of opiate receptors in smooth microsomal fractions isolated from rat brain. PMID- 6268623 TI - Binding of adenosine 3':5'-monophosphate to plasma membranes of Dictyostelium discoideum amoebae. AB - A plasma membrane preparation from Dictyostelium discoideum amoebae which contains the high affinity cAMP receptor is described. Ligand specificity and the kinetics of cAMP association and dissociation using isolated plasma membranes were similar to those of intact cells. The changes in cAMP binding activity which occur as cells proceed through their aggregation program were also reflected in the membrane preparations. However, neither the low affinity cAMP binding site nor the oscillatory cAMP binding behavior observed on intact cells was detected with the membrane preparations. PMID- 6268624 TI - Pulsed EPR studies of peroxide-activated cytochrome c peroxidase and of the mercaptoethanol derivative of Neurospora tyrosinase. AB - We have measured the linear electric field effect for peroxide-activated yeast cytochrome c peroxidase and for the mercaptoethanol derivative of Neurospora tyrosinase. Although both of these materials have EPR spectra resembling those of free radicals, the linear electric field effect measurements demonstrate that there is a metal ion associated with the paramagnetic centers. In addition, we have also observed superhyperfine interactions with 14N nuclei. PMID- 6268625 TI - Reaction of oxygen with cytochrome c oxidase from Paracoccus denitrificans. AB - The reaction of reduced cytochrome c oxidase (EC 1.9.3.1) from Paracoccus denitrificans (American Type Culture Collection 13543) with dioxygen has been followed by laser flash photolysis of the CO derivative. In detergent-stabilized solutions the reaction showed at least two distinct kinetic components, the faster of which was oxygen concentration dependent and had a rate of approximately 60 X 10(6) M-1 s-1. The slower reaction was independent of oxygen concentration and had a rate of 9 X 10(2) s-1. These rates are about 1.5 times greater than comparable rates for ox heart oxidase reported by C. Greenwood and Q. H. Gibson (J. Biol. Chem. (1967) 242, 1782-1787). The kinetic components have markedly different optical spectra which agree precisely in form with those for ox heart enzyme (Greenwood, C., and Gibson, Q. H. (1967) J. Biol. Chem. 242, 1782 1787) but are shifted by 2 nm toward the red. In phospholipid vesicles, the spectral contribution of the faster component was augmented. The dissociation constant for CO at 20 degrees C is 1.6 microM, 6 times greater than for the ox heart enzyme. The bacterial enzyme binds one CO per 2 heme a. The enzyme has an absorption band at 830 nm in the oxidized form similar to that of the ox heart enzyme. PMID- 6268626 TI - Horseradish peroxidase. Complex formation with anions and hydrocyanic acid. AB - Equilibrium binding experiments have been performed with perchlorate, chloride, and acetate in the presence of horseradish peroxidase. The binding of perchlorate and acetate appears to be like that of nitrate, at a site other than the sixth coordination position of the heme iron. Competitive experiments using both nitrate and cyanide demonstrate that two different binding sites are present on the enzyme. Chloride appears to bind at the sixth coordination position as do both fluoride and cyanide. Temperature jump experiments indicate that it is likely the nitrate anion and not undissociated nitric acid which is the binding species. Competitive stopped flow experiments indicate that the bound nitrate slows both the association rate and dissociation rate of cyanide, indicating that nitrate binds close to the sixth coordination position. PMID- 6268627 TI - Does simian virus 40 T antigen unwind DNA? AB - Recently developed techniques allow rapid and accurate determination of protein induced DNA unwinding. We have used such techniques to determine whether SV40 T antigen unwinds DNA. Assays were performed with purified wild type T antigen, D2 protein and the SV80 T protein over a wide range of protein concentrations. Additionally, several DNA templates were used, including SV40 DNA, pBR322 DNA, and two plasmid DNAs containing one and three copies of the SV40 origin of replication. None of the purified proteins showed unwinding activity either in the presence or absence of ATP and Mg2+. As a positive control, we found that unwinding of pBR322 DNA by Escherichia coli RNA polymerase occurred under identical assay conditions. Protein-DNA interactions that involve unwinding of the helix are sensitive to the superhelical density of the DNA. Using a filter binding assay, we found that the efficiency of the binding of T antigen to the viral origin of replication does not depend upon the topological state of the DNA. This result further supports our conclusion that SV40 T antigen is not an unwinding protein. PMID- 6268628 TI - The genes for fifteen ribosomal proteins of Saccharomyces cerevisiae. AB - We have isolated recombinant lambda phage carrying the genes for 14 of the ribosomal proteins of the yeast Saccharomyces cerevisiae. Analysis of these and of the plasmid carrying the gene tcm1, which codes for the ribosomal protein responsible for resistance to trichodermin, demonstrates that in general the genes for ribosomal proteins are unlinked. One exceptional recombinant carries the genes for two ribosomal proteins within a 2-kilobase region. DNA fragments bearing individual ribosomal protein genes were used to probe restriction digests of the yeast genome to determine whether any of the genes were duplicated. Only 3 of 12 of the genes are present unequivocally as a single copy. Similar fragments were used to probe blots of mRNA separated on denaturing agarose gels to determine the size of the mRNA for each protein. In each case, the mRNA is near the minimum size necessary to code for its protein. In certain temperature sensitive mutants which fail to synthesize functional mRNA for ribosomal protein, Rosbash et al. (Rosbash, M., Harris, P. K. W., Woolford, J., and Teem, J. L. (1981) Cell, 24, 679-686) have demonstrated the accumulation of a larger RNA molecule, homologous to a ribosomal protein gene, that appears to be a transcript which retains an intervening sequence. We find that for 8 of the 11 ribosomal protein genes examined, a larger molecule accumulates in such a mutant strain, suggesting that in general transcripts of ribosomal protein genes may have introns. PMID- 6268629 TI - Low density lipoprotein receptor deficiency in cultured hepatocytes of the WHHL rabbit. Further evidence of two pathways for catabolism of exogenous proteins. AB - We have studied hepatocytes cultured from Watanabe-heritable hyperlipidemic (WHHL) rabbits, animals that display striking elevation of plasma low density lipoprotein (LDL), spontaneous atherosclerosis, and an absence of LDL receptor activity in cultured fibroblasts. Degradation of LDL by WHHL hepatocytes differed from degradation by normal hepatocytes in several ways: 1) degradation by normal hepatocytes as a function of LDL concentration was curvilinear with a saturable component, while degradation by WHHL hepatocytes was a linear function of concentration; 2) degradation of 125I-labeled LDL by mutant cells was not decreased by excess unlabeled LDL, while degradation by normal cells was; 3) degradation of LDL by normal cells was inhibited by colchicine and chloroquine while degradation by the mutant cells was not; 4) both cell types catabolized LDL at nearly equal rates, but activity of 3-hydroxy-3-methylglutaryl-CoA reductase was suppressed only in the normal cells. These differences are analogous to those previously reported in describing the qualitatively different pathways for receptor-dependent and receptor-independent catabolism of lactosylated and native human LDL in rat hepatocytes. Thus, hepatocytes from WHHL rabbits lack LDL receptor activity. The peripheral and hepatic LDL receptors most likely are products of the same gene or depend for their activity on a single gene product. PMID- 6268630 TI - Activation of adenylate cyclase by the diterpene forskolin does not require the guanine nucleotide regulatory protein. AB - Forskolin, a novel diterpene activator of adenylate cyclase in membranes and intact cells, activates the enzyme in membranes from mutant cyc-S49 murine lymphoma cells and the soluble enzyme from rat testes. Each of these enzymes consists only of the catalytic subunit and does not have a functional guanine nucleotide-binding protein. In both cases forskolin converts the manganese dependent enzymes to a form which does not require manganese for activity. Forskolin can also stimulate a detergent-solubilized preparation of adenylate cyclase from rat cerebral cortex. Activation of adenylate cyclase by forskolin is therefore not dependent on a perturbation of membrane structure nor does it require a functional guanine nucleotide-binding subunit. PMID- 6268631 TI - Interaction of receptor for intrinsic factor-cobalamin complex with synthetic and brush-border lipids. AB - The intestinal receptor for intrinsic factor-cobalamin complex integrates preferentially with cationic liposomes in such a way that its ligand binding sites are exposed to proteases and to antibody to the receptor. After integration the receptor could be solubilized from the liposomes by detergents and chaotropic salts. Kinetically, the brush-border and the liposome-bound receptor behaved similarly, and Triton X-100 had no effect either on Ka or Vmax, suggesting the absence of any effects of a lipid domain on ligand binding activity. However, acidic phospholipids caused inhibition when added to the receptor-ligand assay system in the absence of liposomes. PMID- 6268632 TI - Physical characterization of the transferrin receptor in human placentae. AB - The physical properties and binding characteristics of the solubilized transferrin receptor isolated from the placental brush-border membrane of a human trophoblast cell were investigated. The receptor protein was isolated from solubilized 125I-labeled membranes by immunoprecipitation with anti-human transferrin in the presence of saturating amounts of human transferrin. Gel filtration on acrylamide agarose (AcA-22) at 23 degrees C in the absence of transferrin indicates the transferrin receptor has a Stokes radius of 4.6 nm. In the presence of transferrin, the Stokes radius of the receptor shifts to 6.3 nm. Sucrose density centrifugation studies indicate that it has a sedimentation coefficient of 9.8 S in the absence of transferrin and 11.2 S in the presence of transferrin. The molecular weight for the transferrin free receptor is calculated to be 213,000. Upon incubation with transferrin, it increases to 364,000. This is consistent with the idea that the active form of the solubilized receptor is a dimer and the dimer is in turn capable of binding two transferrin molecules. PMID- 6268633 TI - Calmodulin activates the isolated catalytic unit of brain adenylate cyclase. AB - The catalytic and guanine nucleotide regulatory (G/F) units of solubilized bovine brain adenylate cyclase were separated by gel filtration as described by Strittmatter, S., and Neer, E. J. ((1980) Proc. Natl. Acad. Sci. U. S. A. 77, 6344-6348). The isolated catalytic unit is activated 4 +/- 1-fold (n = 11) by pure bovine brain calmodulin and is stabilized by calmodulin against thermal inactivation. The separated G/F unit can be freed of endogenous calmodulin by gel filtration in buffer containing 1 mM EDTA and no divalent cations. The calmodulin free G/F unit still activates the catalytic unit. Re-addition of calmodulin does not affect the rate or extent of activation of the G/F unit by guanosine 5' (beta, gamma-imino)triphosphate. The activation by calmodulin and the G/F unit together is additive, not synergistic. These studies show that calmodulin interacts with the adenylate cyclase catalytic unit but does not seem to affect the function of the G/F unit. PMID- 6268634 TI - Characterization of photoaffinity labeling of benzodiazepine binding sites. AB - The specific photoaffinity labeling of membrane-bound and detergent-solubilized benzodiazepine binding sites has been investigated using UV irradiated [3H] flunitrazepam as a photochemical probe. The time course and the regional and pharmacological specificity of the photolabeling reaction has been determined for "brain-specific" benzodiazepine binding sites; "peripheral-type" binding sites treated in an identical manner were not specifically labeled. Comparison of the number of sites labeled and blocked by [3H]flunitrazepam photolabeling of detergent-solubilized preparations indicated that about one site was blocked and unavailable for reversible binding for each site photolabeled. In contrast, when membrane-bound sites were photolabeled, about four sites were inactivated for each site photolabeled. Examination of photolabeled binding sites from various brain regions including cortex, striatum, and hippocampus using sodium dodecyl sulfate-polyacrylamide gel electrophoresis gave only a single labeled band of apparent Mr = 48,000. PMID- 6268636 TI - Purification and characterization of rat liver alpha-N-acetylglucosaminyl phosphodiesterase. AB - In an earlier report we described the identification of an alpha-N acetylglucosaminyl phosphodiesterase that is capable of cleaving the outer phosphodiester-linked alpha-N-acetylglucosamine residues present on the high mannose oligosaccharides of newly synthesized lysosomal enzymes (Varki, A., and Kornfeld, S. (1980) J. Biol. Chem. 255, 8398-8401). We have now purified this enzyme 1800-fold with a 24% yield from rat liver, using subcellular fractionation, differential extraction with Triton X-10, DEAE-cellulose chromatography, heparin-Sepharose chromatography, concanavalin A-Sepharose affinity chromatography, and gel filtration on Sephacryl S-300. The purified preparation is free of lysosomal alpha-N-acetylglucosaminidase. The enzyme exhibited a single form on both the ion exchange and gel filtration steps. It has a broad pH optimum between 6.0-8.0 and is unaffected by divalent cations or reducing agents. The enzyme cleaves alpha-N-acetylglucosamine residues from five different locations on the high mannose oligosaccharide. In the case of molecules with one phosphodiester, the rate of cleavage is not affected by the size of the underlying oligosaccharide or the presence or absence of an asparagine-linked peptide. Molecules with two phosphodiesters are cleaved in a nonrandom manner. The enzyme has no activity toward p-nitrophenyl-alpha-N-acetylglucosamine but is capable of cleaving phosphodiester-linked N-acetylglucosamine in molecules such as UDP-N-acetylglucosamine, indicating that it can only hydrolyze N acetylglucosamine residues that are alpha-linked to a phosphate group. PMID- 6268635 TI - The kinetics of neutrophil activation. The response to chemotactic peptides depends upon whether ligand-receptor interaction is rate-limiting. PMID- 6268638 TI - Tumoral calcinosis. Report of a case with successful medical management. PMID- 6268637 TI - A novel, highly modified, bacteriophage DNA in which thymine is partly replaced by a phosphoglucuronate moiety covalently bound to 5-(4',5' dihydroxypentyl)uracil. AB - Bacteriophage SP-15, which infects Bacillus subtilis, contains a highly modified DNA in which 62% of its thymine residues are replaced by 5-(4',5' dihydroxypentyl)uracil to which is attached a phosphoglucuronate via a phosphodiester linkage to one of the hydroxyl groups of the pentyl side chain. Glucose is also bound to this residue probably by glycosidic linkage to the other hydroxyl group of the pentyl side chain. In 0.3 M KOH at 37 degrees C, glucuronic acid 1-phosphate is slowly released from this DNA. After enzymatic or acid induced dephosphorylation, this sugar was identified by chromatography in two thin layer chromatography systems, conversion to glucuronolactone under conditions known to lactonize glucuronic acid, and reaction in four colorimetric assays for hexuronic acids. Phage SP-15 DNA is the first DNA found to have a uronic acid moiety or a phosphate which is not part of the phosphodiester backbone. The glucuronic acid phosphate might be derived from uridine pyrophosphoglucuronic acid, whose glucuronic acid moiety is normally destined for synthesis of teichuronic acid in the host cell wall. PMID- 6268639 TI - Electron-microscopic morphology of virus replication in cells of the murine Borstel-leukemia X 429. AB - Intraperitoneal injections of cell-free filtrates of Borstel-leukemia X 429 (immature-cell myeloid leukemia induced by 200 rad whole-body X-irradiation) were given to 330 1-week-old NMRI mice of both sexes. Leukemia developed in 21% after injection of cell-free filtrates from leukemic spleens and in 20% after injection of cell-free filtrates from leukemic lymph nodes. The mean time lapse from injection to the appearance of the leukemia was 12.8 months. The virus replication in the newly formed leukemic cells, was studied by electron microscopy. Special attention was given to the relation between A-particles and mature type-C viruses. The leukemia cells contain intracytoplasmic and intracisternal A-particles consisting of two concentric spherical shells with an external diameter of 70 nm. A-particles present mainly as closed "virus fields" in the vicinity of the cell nucleus, frequently in the Golgi area. The intracisternal A-particles appear inside the lumen of expanded vesicles of the cytoplasma. Typ-C viruses develop on the cytoplasmic membrane and/or on the outer cell membrane by condensation of crescent-shaped electron-dense zones. All layers of the later mature virus are recognisable in these early morphological stages. After the virus has been detached from the cell it collapses, and the outer membrane appears wrinkled. No spatial correlation between the storage sites of the A-particles and the sites of formation of mature type-C viruses are demonstrable. PMID- 6268640 TI - Malignant fibrous histiocytoma of the renal capsule. AB - We report about an extremely rare case of malignant fibrous histiocytoma (MFH) of the renal capsule. The tumor is composed of fibroblast-like cells arranged in a storiform pattern and histiocyte-like cells with multinucleated giant cells, both showing no iron reaction. Characteristic of the histiocytic quality of the tumor are numerous PAS-positive intracytoplasmic droplets which can be identified as erythrophagosomes only under the electron microscope. Emphasis is put on the preoperative differential diagnosis of the tumor from renal cell carcinoma as well as on its histogenesis and prognosis. PMID- 6268641 TI - Inhibitory effect of a revertant cell on in vivo growth of its parental transformed cell line. AB - A revertant cell line, KSR-4111, cloned from a sarcoma virus transformed non virus producing murine 3T3 cell line, K-BALB-23, was found to inhibit in vivo growth in newborn syngeneic mice of the transformed cells when grafted to the same locus, but not when grafted separately from the grafted tumor cells. No inhibition of outgrowth of the transformed K-BALB-23 cells was obtained with another revertant, KSR-12121, also cloned from the transformed K-BALB-23 cell, nor with the normal 3T3 cell. Furthermore, grafting of two syngeneic mammary tumors was unaffected by the presence of the protective revertant cells. The protective revertant KSR-4111 was furthermore characterized by inducing cytoxic non-theta-antigen-bearing spleen lymphocytes in grafted syngeneic recipients. PMID- 6268642 TI - Studies on the surface properties of hybrid cells. III. A membrane glycoprotein found on the surface of a wide range of malignant cells. AB - We report here the presence of a glycoprotein of apparent molecular mass 90000 daltons on the surface of membranes of malignant cells, which is absent or very much reduced on the surface of non-malignant cells. This glycoprotein is rich in sialic acid and appears to be sensitive to the concentration of cAMP under certain conditions. Analysis of the labelled sugars present in the glycoproteins of cells metabolically labelled with [14C]glucosamine suggests that all the enzymes necessary for the conversion of the tracer precursor into the sugars normally found to be labelled are present in both the malignant and the non malignant cells. PMID- 6268643 TI - Cell surface marker proteins during mouse spermatogenesis: two-dimensional electrophoretic analysis. AB - Purified plasma membranes isolated from separated highly homogenous populations of mouse pachytene spermatocytes, round spermatids (step I-8), and residual bodies have been compared using 2-dimensional polyacrylamide gel electrophoresis. Two polypeptides apparently specific to pachytene spermatocytes have been identified. Component Pa has a molecular weight of 90 k daltons (K) and pI of 5.6. Component Pb has a molecular weight of 56.5 K and a pI of 6.0. Four polypeptides detected only in plasma membranes of round spermatids have been identified as follows: RSa, 90-95 K and pI 5.9; RSb, also 90-95 K and pI 5.9; RSc, approximately 88 K and pI 5.5; RSd, 58 K and pI 6.0-6.3. No polypeptides unique to residual body membranes were identified. Short-term culture experiments have established that separated adult mouse spermatogenic cells survive short term culture in vitro. These cells actively synthesize numerous cellular proteins as determined by the incorporation of [3H]leucine. Investigations concerning the effect of the cell separation procedure on mouse spermatogenic cell membranes indicate that only 7 of 110-120 total plasma membrane constituents are degraded enzymically during cell purification. Only one of these constituents may correspond to the presumptive cell differentiation markers described for pachytene spermatocytes and round spermatids. These results indicate, therefore, that plasma membranes obtained immediately after cell separation are suitable for the detailed biochemical analysis of the most integral surface proteins during spermatogenesis in the mouse. PMID- 6268644 TI - Organotypic cultures of the avian salt gland: biosynthesis of membrane proteins. AB - The salt glands of control and salt-stressed ducklings were dissociated with collagenase to produce cell aggregates or 'minilobules' which were cultured. The fine-structural organization of freshly isolated and cultured (up to 72 h) aggregates were examined and showed surprisingly intact fine-structural organization with minimal changes from untreated glands. Incorporation of [3H]leucine into total protein, membrane protein and immunoprecipitable Na,K ATPase was determined in cultures at various time points, by pulse or pulse-chase experiments. Incorporation of label was linear for 4 h in protein, but higher in cultures of salt-stressed glands than in controls. Na,K ATPase was synthesized throughout the time of the experiment, the rate being highest during the first 4 h, reaching a plateau by 24 h. Up to 10% of the total label was present in Na,K ATPase. These results are discussed with reference to the use of minilobule culture to analyse further synthesis and assembly during biogenesis and control of these processes. PMID- 6268645 TI - Detection and differentiation of cytomegalovirus antibodies by radioimmunoassay. AB - A sensitive radioimmunological method was adapted for the assay of anticytomegalovirus IgG and IgM antibodies. Binding of immunoglobulins G with cytomegalovirus (CMV) antigens was greatly reduced when an antigen prepared by sonication of the infected cells in glycine buffer was used in place of the antigen obtained by freezing and thawing of the cells. The application of labelled serum against the Fc fragment of IgG made it possible to identify selectively the antibodies bound with the virus antigen by antigenic determinants. PMID- 6268646 TI - Selection of somatic cell hybrids between BK virus transformed BHK-21 and human embryonic kidney cells to study viral gene expression. AB - Somatic cell hybrids were constructed between the human papovavirus, BKV, transformed BHK-21 cells and human embryonic kidney cells, the permissive host for BKV using the polyethylene glycol-DMSO cell fusion method. Hybrids were selected to preserve the phenotype of transformation as anchorage independence to allow examination of the synthesis of BKV early gene products, the T proteins. Several hybrid clones which survived the selection procedure demonstrated an enhanced production of the small t or approximately 22 K protein while the viral large T or approximatley 94 K protein was not detectable. It was also determined in this study that BHK-21 cells which are thymidine kinase deficient (TK-) can be stably transformed by BKV and appear to remain enzyme deficient after transformation. PMID- 6268648 TI - An electrophoretic method for the detection of replicating, supercoiled simian virus 40 DNA. PMID- 6268647 TI - Efficient production of mammalian RNA tumor viruses in serum-free culture medium allows rapid RNA subunit purification. AB - A wide variety of infected mammalian cell cultures were observed to produce high levels of RNA tumor virus particles in the absence of serum for at least 12 h. Virus production was measured by yields of 50-70 S virus RNAs isolated directly from serum-free culture media by chromatography on oligo(dT)-cellulose. Yields of RNAs from viruses produced in serum-free medium were comparable to yields obtained from purified viruses produced in serum-containing medium. Subunits of viral RNAs were thermally dissociated and separated by a new sedimentation system using sucrose gradients with resolving power (in the relevant size range) equivalent to that obtained with electrophoresis in polyacrylamide gels. RNA subunits isolated directly from serum-free medium appeared to be intact as judged by poly(A) content and resedimentation. The overall approach developed here represents dramatic savings in time and effort over previous ways of producing purified RNA subunits from tumor viruses. PMID- 6268649 TI - The development and evaluation of a solid-phase radioimmunoassay (RIA) procedure for the determination of susceptibility to varicella. AB - The development of a sensitive solid-phase radioimmunoassay (RIA) procedure for the detection of specific antibodies against varicella-zoster (VZV) is described. The test proved to be about 200 times more sensitive than complement fixation (CF) and far more efficient at detecting low levels of antibody in the sera of individuals with past history of varicella. It is suggested that this RIA-VZV test would be suitable for distinguishing between individuals who are either immune or susceptible to varicella, which could be useful in a variety of clinical situations but particularly in current and future evaluations of varicella vaccines. PMID- 6268650 TI - The use of markers in immune electron microscopy. AB - Immune electron microscopy (IEM) cannot be used successfully for structures that do not have recognisable morphology. However, at least some of these structures or components are related antigenically to recognisable antigens or viruses. We have therefore mixed unknown antigens with known markers and looked for the presence of mixed aggregates. The present study examined a low molecular weight subunit of rotavirus and a micellar form of hepatitis B surface antigen. In both cases mixed immune aggregates were found showing that the unknown components had antigens in common with the established virus or antigen. PMID- 6268651 TI - The preparation of orthopoxvirus DNA. PMID- 6268652 TI - Comparison of immunosorbent electron microscopy, enzyme immunoassay and counterimmunoelectrophoresis for detection of human rotavirus in stools. AB - The detection of human rotaviruses by routine electron microscopy examination of stool specimens has been compared with the sensitivity of detection obtainable by three different immunoassays. These assays are: 1) immunosorbent electron microscopy (ISEM), which consists of the serological trapping of viruses on electron microscopy grids coated with protein A and specific viral antiserum; 2) an enzyme-linked immunosorbent assay (ELISA), in which the primary antibody is rabbit anti-rotavirus immunoglobulin, the secondary antibody is chicken anti rotavirus immunoglobulin extracted from egg yolk of immunized hens, and the indicator antibody is alkaline phosphatase-conjugated rabbit anti-chicken immunoglobulin; 3) counterimmunoelectrophoresis (CIE). A total of 63 stool specimens from infants with gastroenteritis were examined. Of these, 23 and 24 specimens were found to contain rotavirus by electron microscopy and CIE, respectively. When scored by ELISA and ISEM, 37 and 39 were found to be positive, respectively. Confirmatory inhibition assays were necessary to eliminate some false positive reactions in ELISA. Detection of human rotaviruses in stools by ISEM is as sensitive as by ELISA, but in weakly positive specimens, ISEM offers the additional advantage of a direct visual demonstration of the presence of the aetiological agent. PMID- 6268653 TI - Direct immunofluorescence staining for detection of herpes simplex and varicella zoster virus antigens in vesicular lesions and certain tissue specimens. AB - Direct immunofluorescence (IF) staining was compared with virus isolation for detection of herpes simplex viruses (HSV) and varicella-zoster virus (VZV) directly in clinical materials. These included 199 vesicular lesion specimens and 280 tissue specimens. Correspondence between IF and isolation results was 88% in testing for HSV in lesion specimens and 98% in testing for HSV in various tissue (mostly brain) specimens. Overall, IF was positive for 82% of the specimens in which HSV was demonstrated, and virus was isolated from 89% of the HSV-positive specimens. IF was markedly more sensitive than isolation for demonstrating VZV in lesion and tissue specimens, detecting all of the specimens positive for VZV, whereas isolation detected only 23%. IF detected VZV antigen in a number of lesion specimens taken late after onset, past the time when they would be expected to yield infectious virus. Specificity of positive IF reactions for HSV or VZV in the absence of virus isolation was supported by the facts that (i) staining was obtained with only a single, presumably homologous, immune conjugate, (ii) clinical symptoms were compatible with infection with the virus for which positive IF findings were obtained, and (iii) positive electron microscopy findings for herpesviruses or positive serological results for VZV were also obtained in some instances. Factors to be considered in achieving specificity of IF staining for these human herpesviruses are discussed. PMID- 6268654 TI - Enzyme-linked immunosorbent assay for immunoglobulin G antibody to encephalomyocarditis virus. AB - An enzyme-linked immunosorbent assay for immunoglobulin G antibody to encephalomyocarditis virus was developed. This assay was comparable to antibody assay by neutralization. Its adaptability should be useful for laboratory and epidemiological studies of infections due to encephalomyocarditis virus. PMID- 6268655 TI - Visual reading of enzyme immunofluorescence assays for human cytomegalovirus antibodies. AB - Enzyme immunofluorescence assays for cytomegalovirus antibodies could be read satisfactorily using a light box with ultraviolet illumination. Higher antibody titers were obtained with a fluorogenic substrate than with a color-producing substrate. PMID- 6268657 TI - Hydrolytic enzymes of anaerobic bacteria isolated from human infections. AB - Thirty-three strains of anaerobic bacteria isolated from human clinical specimens were examined for the presence of heparinase, hyaluronidase, chondroitin sulfatase, gelatinase, collagenase, fibrinolysin, lecithinase, and lipase activities. Pronounced heparinase activity was limited to species of the genus Bacteroides. A number of species of the genera Bacteroides and Clostridium produced hyaluronidase and chondroitin sulfatase. Gelatinase, collagenase, and fibrinolysin activities were encountered in isolates of the genera Bacteroides, Clostridium, and Peptostreptococcus. All strains capable of degrading collagen also hydrolyzed other protein substrates. Lipolytic activity was minimal among these anaerobic bacteria. No specific hydrolytic activity was consistently associated with the isolates. PMID- 6268656 TI - Acute diarrhea and rotavirus infection in newborn babies and children in Yogyakarta, Indonesia, from June 1978 to June 1979. AB - A longitudinal study of acute diarrhea in children in Yogyakarta, Indonesia (June 1978 to June 1979), showed little variation throughout most months of the year in numbers of children admitted to hospital and in numbers infected with rotaviruses. Both decreased during November and December coincidentally with seasonal change from dry to wet conditions. Rotavirus particles were identified by electron microscopy in fecal specimens from 126 of 334 (38%) infants and children with acute diarrhea. Nosocomial rotavirus infections occurred in 11% of control children admitted to hospital for other reasons. Socioeconomic level and preexisting nutritional status did not influence the incidence of rotavirus excretion. Rotavirus infections were most common in children aged 6 to 24 months. There was a low incidence of infection in infants less than 6 months old. Rotavirus infection was seldom observed in newborn babies delivered in an urban hospital nursery, in a rural health center, or at home. One of 72 newborn babies with diarrhea excreted rotavirus. One of 53 healthy newborn babies excreted rotavirus. It is concluded that, in Indonesia, rotavirus infection is a major cause of childhood diarrhea throughout the year, but is an uncommon cause of diarrhea in newborn babies. PMID- 6268658 TI - Improved detection of viruses by electron microscopy after direct ultracentrifuge preparation of specimens. AB - We have adapted the Beckman Airfuge air turbine ultracentrifuge and the new EM-90 particle-counting rotor to improve detection by electron microscopy of viruses in clinical specimens. Samples were clarified by centrifugation, pelleted in the EM 90 rotor directly to Formvar-coated copper grids, and strained with 1.5% sodium phosphotungstate. Virus counts and endpoint titrations of serial dilutions of partially purified preparations of poliovirus, SA11 rotavirus, herpes simplex virus, and vaccinia virus showed an increase of ca. 1.5 log10 to 3.0 log10 over the virus titers of unconcentrated preparations of the same material. An increased yield of 14% more positive specimens for rotavirus was obtained after preparation of clinical samples by direct ultracentrifugation versus a method without virus concentration (82 versus 72). A prospective study showed that detection of adenoviruses, herpesviruses, and enteroviruses increased when specimens were prepared by direct ultracentrifugation. Direct ultracentrifugation with the EM-90 rotor in the Airfuge ultracentrifuge is a rapid concentration method which enhances the rate and yield of virus detection from clinical specimens by electron microscopy and is easily adaptable to a diagnostic virology laboratory. PMID- 6268659 TI - Immunization of inbred guinea pigs with varicella-zoster virus grown in a syngeneic transformed embryo cell line. AB - Varicella-zoster virus was serially propagated in a chemically transformed and cloned line of embryo cells (designated "104 C1") derived from the inbred strain 2 guinea pig. When strain 2 guinea pigs were immunized with varicella-zoster virus subcultivated in the syngeneic cell line, they produced high-titer virus specific antiserum which lacked antibody against cellular determinants. This immunization procedure offers both practical and theoretical advantages over prior methods which involved inoculation of outbred laboratory animals with varicella-zoster virus grown in allogeneic or xenogeneic cell cultures. PMID- 6268660 TI - Sickle gene. Its origin and diffusion from West Africa. AB - Linked DNA polymorphisms can be used to study the evolution of structural gene mutations. Both the beta S-(beta 6Glu leads to Val) and beta C-(beta 6Glu leads to Lys) genes are common in West Africa. We have analyzed their linkage to a polymorphic Hpa 1 site appearing 3' to the beta-globin gene locus in selected populations from Wes Africa. A large reservoir of beta A-genes linked to 13 kilobase Hpa 1 fragments with a frequency of 17-18% has been identified. In addition, the beta S- and beta C-genes in Togo are found to be tightly linked to the 13-kilobase Hpa 1 fragment, whereas 72% of the beta S-genes in the Ivory Coast reside on the 7.6-kilobase Hpa 1 fragment. These studies are consistent with the selection and expansion of two different chromosomes bearing beta S genes in at least two physically close, but ethnically separate regions of West Africa, with subsequent diffusion to North, Equatorial, and East Africa. PMID- 6268661 TI - Monocyte chemotactic peptide receptor. Functional characteristics and ligand induced regulation. AB - Monocytes, macrophages, and neutrophils will demonstrate several important cellular functions in response to synthetic formylated oligopeptides. N-formyl norleucyl-leucyl-phenylalanyl-norleucyl-tyrosyl-lysine (fNLPNTL) was a potent chemoattractant for human blood monocytes; a 1.0-nM concentration induced a maximal chemotactic response. Binding of 125I-labeled fNLPNTL to the monocyte formyl peptide receptor was rapid, specific, and saturable at 4, 24, or 37 degrees C. At 4 degrees C, monocytes from several different donors demonstrated between 10,000 and 18,000 receptors/cell with a dissociation constant (Kd) of 1.7 2.7 nM. The association of the 125I peptide with the cells was irreversible at the elevated temperatures and exceeded the amount of surface receptor by approximately four-fold, suggesting receptor-mediated peptide endocytosis. Processing of rhodamine-labeled fNLPNTL by monocytes was observed directly by video intensification microscopy. At 37 degrees C, diffuse membrane fluorescence was seen initially, followed by rapid aggregation and internalization of the peptide. Monocytes incubated with fNLPNTL displayed a temperature dependent loss of surface binding capacity (receptor down-regulation). This decrease was due to a decrease in surface receptor number rather than to a decrease in receptor affinity. A dose-response curve for peptide-induced receptor down-regulation correlated with a dose-response curve for 125I-labeled fNLPNTL uptake, suggesting that each uptake event led to the loss of one surface receptor. Surface receptor replenishment following down-regulation was rapid and not dependent on new protein synthesis, but was inversely related to both the time and peptide concentration used to induce down-regulation. An exact correlation between receptor down-regulation and functional deactivation of the chemotactic response could not be demonstrated. PMID- 6268662 TI - Role of hydrogen peroxide in neutrophil-mediated destruction of cultured endothelial cells. AB - Human neutrophils stimulated with phorbol myristate acetate were able to destroy suspensions or monolayers of cultured human endothelial cells. Neutrophil mediated cytotoxicity was related to phorbol myristate acetate concentration, time of incubation and neutrophil number. Cytolysis was prevented by the addition of catalase, while superoxide dismutase had no effect on cytotoxicity. The addition of the heme-enzyme inhibitors, azide or cyanide, markedly stimulated neutrophil-mediated damage while exogenous myeloperoxidase failed to stimulate cytolysis. Neutrophils isolated from patients with chronic granulomatous disease did not destroy the endothelial cell targets while myeloperoxidase-deficient neutrophils successfully mediated cytotoxicity. Endothelial cell damage mediated by the myeloperoxidase deficient cells was also inhibited by catalase but not superoxide dismutase. The addition of purified myeloperoxidase to the deficient cells did not stimulate cytotoxicity. Glucose-glucose oxidase, an enzyme system capable of generating hydrogen peroxide, could replace the neutrophil as the cytotoxic mediator. The addition of myeloperoxidase at low concentrations of glucose oxidase did not increase cytolysis, but at the higher concentrations of glucose oxidase it stimulated cytotoxicity. The destruction of endothelial cells by the glucose oxidase-myeloperoxidase system was inhibited by the addition of hypochlorous acid scavengers. In contrast, neutrophil-mediated cytolysis was not effectively inhibited by the hypochlorous acid scavengers. Based on these observations, we propose that human neutrophils can destroy cultured human endothelial cells by generating cytotoxic quantities of hydrogen peroxide. PMID- 6268664 TI - Congenital mesoblastic nephroma with cystic component. PMID- 6268665 TI - Further observations on the sonographic spectrum of gestational trophoblastic disease. AB - Sonograms of 27 patients with gestational trophoblastic disease were evaluated and categorized to newer concepts regarding the pathology and pathogenesis of this disorder. The patients were assigned to the following subgroups: 1) classical or complete mole; 2) partial or incomplete mole; 3) coexistent mole and fetus; 4) hydropic degeneration of the placenta; 5) locally invasive mole; and 6) metastatic trophoblastic disease, including choriocarcinoma. The utility of this categorization and of ultrasound in the diagnosis and subsequent management of these patients is presented. PMID- 6268663 TI - Effects of beta-lipotropin and beta-lipotropin-derived peptides on aldosterone production in the rat adrenal gland. AB - To investigate the role of non-ACTH pituitary peptides on steroidogenesis, we studied the effects of synthetic beta-lipotropin, beta-melanotropin, and beta endorphin on aldosterone and corticosterone stimulation using rat adrenal collagenase-dispersed capsular and decapsular cells. beta-lipotropin induced a significant aldosterone stimulation in a dose-dependent fashion (10 nM-1 muM). beta-endorphin, which is the carboxyterminal fragment of beta-lipotropin, did not stimulate aldosterone production at the doses used (3 nM-6 muM). beta melanotropin, which is the middle fragment of beta-lipotropin, showed comparable effects on aldosterone stimulation. beta-lipotropin and beta-melanotropin did not affect corticosterone production in decapsular cells. Although ACTH(1-24) caused a significant increase in cyclic AMP production in capsular cells in a dose dependent fashion (1 nM-1 muM), beta-lipotropin and beta-melanotropin did not induce an increase in cyclic AMP production at the doses used (1 nM-1 muM). The beta-melanotropin analogue (glycine[Gly](10)-beta-melanotropin) inhibited aldosterone production induced by beta-lipotropin or beta-melanotropin, but did not inhibit aldosterone production induced by ACTH(1-24) or angiotensin II. Corticotropin-inhibiting peptide (ACTH(7-38)) inhibited not only ACTH(1-24) action but also beta-lipotropin or beta-melanotropin action; however it did not affect angiotensin II-induced aldosterone production. (saralasin [Sar](1); alanine [Ala](8))-Angiotensin II inhibited the actions of beta-lipotropin and beta-melanotropin as well as angiotensin II. These results indicate that (a) beta lipotropin and beta-melanotropin cause a significant stimulation of aldosterone production in capsular cells, (b) beta-lipotropin and beta-melanotropin have a preferential effect on zona glomerulosa cells, (c) beta-melanotropin contains the active peptide core necessary for aldosterone stimulation, (d) the effects of these peptides on aldosterone production may be independent of cyclic AMP, and (e) the receptors for beta-lipotropin or beta-melanotropin may be different from those for ACTH or angiotensin II. PMID- 6268666 TI - Germ cell tumours of childhood: a review of 137 cases. AB - One hundred and thirty-seven germ cell tumours occurring in 134 children included in the Manchester University Children's Tumour Registry over a 25-year period have been studied. The incidence and sites of these tumours as seen in a comprehensive population-based registry are presented and the relation between the primary site and histological type is assessed. There were 48 deaths in this series of which 34 were directly due to the tumour. The cause of death in the other 14 cases is given. The behaviour of the germ cell tumours was closely related to the presence of yolk sac elements. PMID- 6268668 TI - Tyrosine crystals in salivary gland tumours. AB - Tyrosine crystals were seen in 24 of 113 salivary gland pleomorphic adenomas from Malawi and one of six carcinomas arising in a pleomorphic adenoma; they were present in tumours from all common anatomical sites. They were not found in 71 other salivary tumours of varying histological type. Similar crystals were found in one out of 56 pleomorphic adenomas from patients operated on at St Thomas's Hospital. No excess tyrosine was demonstrated in a tumour containing many crystals. Their great frequency in black patients is confirmed but an adequate explanation for this phenomenon has not been found. PMID- 6268667 TI - A new serotype of calicivirus associated with an outbreak of gastroenteritis in a residential home for the elderly. AB - An outbreak of gastroenteritis involving residents and members of staff in a nursing home for the elderly is described. The agent associated with this episode was a calicivirus which is serologically distinct from two strains causing gastroenteritis in children. We believe that this is the first report of calicivirus infection in adults. PMID- 6268669 TI - Fatal dissemination of cytomegalovirus after bone marrow transplantation. AB - The clinical course and necropsy findings are described of an 11-year-old child found to have active cytomegalovirus infection at the time of bone marrow transplantation for acute lymphoblastic leukaemia. Attention is drawn to the presence of primitive mononuclear cells of uncertain origin in the regenerating bone marrow. PMID- 6268670 TI - Comparison of the effect of trisodium phosphonoformate on the mean plaque size of pseudorabies virus, infectious bovine rhinotracheitis virus and pigeon herpesvirus. PMID- 6268671 TI - Drug- and heavy metal--induced hyperpigmentation. AB - Several categories of chemical and pharmacologic agents can cause alterations in cutaneous pigmentation, although the mechanisms differ and in several instances may be unknown. Fixed drug eruptions appear to have alteration of the basement membrane zone with incontinence of epidermal pigment as the mechanism of hyperpigmentation. Heavy metals produce increased pigmentation in part from deposition of metal particles and in part from an increase in epidermal melanin production. The antimalarials may bind to melanin. The phenothiazines and minocycline produce pigmentation from deposition of the drug. The mechanism, site, and nature of the pigment occurring with antineoplastic agents is not well understood, but the location is most likely predominantly epidermal. Clofazimine (Lamprene) alteration in pigmentation appears to result from deposition of the drug in subcutaneous fat. PMID- 6268672 TI - Physiological control of mammary growth, lactogenesis, and lactation. PMID- 6268674 TI - Utilization of hydroxyapatite adsorbable salivary proteins as growth substrates for plaque-forming oral streptococci. AB - Following treatment with hydroxyapatite, clarified mixed saliva from one donor source lost much of its growth-supportive activity for S. mutans VA-29R (type c). Growth of the organism in a basal medium containing proteins desorbed from HA with 0.067 M potassium phosphate buffer, pH 8.0, was accompanied by the disappearance of some of the proteins, including those with isoelectric points of 4.90, 5.72, and 6.00. These proteins are among those known to be specifically attacked by S. mutans. These findings suggest that some of the proteins selectively adsorbed from saliva with HA may serve as specific growth substrates for the plaque-forming oral streptococci. PMID- 6268673 TI - Twenty-five years of progress in understanding major infectious diseases of dairy cattle. PMID- 6268675 TI - Extirpation of a nidus of infection with tetanus bacilli by chemosurgery. PMID- 6268676 TI - Axillary Paget's disease. PMID- 6268678 TI - Profile of a young achiever: Dr. Eve Elizabeth Slater. PMID- 6268677 TI - [Magnetic relaxation of the nonwater fractions of protons in normal and tumorous tissues]. PMID- 6268679 TI - Sex role stereotypes and medical specialty choice. PMID- 6268680 TI - Series on endocrine-metabolic emergencies: IV. Thyroid storm. PMID- 6268682 TI - The missing zinc. PMID- 6268681 TI - Radioiodine treatment during pregnancy: chromosomal aberrations and cretinism associated with maternal iodine-131 treatment. PMID- 6268683 TI - Spin label reduction kinetics, a procedure to study the effect of drugs on membrane permeability: the effects of monosodium urate, dimethyl sulfoxide and amphotericin B. AB - A method is presented to study the effect of drugs on membrane permeability. It is based on the reduction of a spin label trapped in the internal aqueous compartment(s) of membranes by ascorbate ions added to the bulk aqueous phase. The decay of the electron spin resonance signal of the spin label as a function of time gives an indication of the effect of added agents on the permeability of membranes. To demonstrate the technique, the effect on model membranes of egg phosphatidylcholine of the gout-implicated compound monosodium urate, the aprotic solvent dimethyl sulfoxide and the polyene antibiotic amphotericin B were examined. Monosodium urate did not affect the permeability, casting doubt on a proposed mechanism whereby the agent disrupts the membranes via hydrogen bonding. Dimethyl sulfoxide promoted a gradual increase in rate of solute passage across cholesterol-containing model membranes. Amphotericin B had a pronounced effect on the permeability of cholesterol-containing membranes, causing nearly total loss of paramagnetism immediately after addition. Some aspects of the mechanism of action of the drugs are discussed as well as the advantages and disadvantages of the method. The experiments also allow the evaluation of the effect of surface charge and cholesterol on the dimensions of model membranes. PMID- 6268684 TI - Organization of the sacral parasympathetic reflex pathways to the urinary bladder and large intestine. AB - Electrophysiological and horseradish peroxidase (HRP) techniques have provided new insights into the organization of the sacral parasympathetic reflex pathways to the large intestine and urinary bladder. The innervation of the two organs arises from separate groups of sacral preganglionic cells: (1) a dorsal band of cells in laminae V and VI providing an input to the intestine; and (2) a lateral band of cells in lamina VII providing an input to the bladder. These two groups of cells were separated by an interband region containing tract cells and interneurons. Neurons in the interband region received a visceral afferent input and exhibited firing correlated with the activity of intestine and urinary bladder. It seems reasonable therefore to consider the interband region as a third component of the sacral parasympathetic nucleus. Anterograde transport of HRP revealed that visceral afferents from the intestine and bladder projected into the parasympathetic nucleus. Most of the projections were collaterals from afferent axons in Lissauer's tract that passed in lamina I laterally and medially around the dorsal horn. These afferent collaterals were located in close proximity to preganglionic perikarya and dendrites in laminae I, V and VI. The proximity of visceral afferents and efferents in the sacral cord probably reflects the existence of polysynaptic rather than monosynaptic connections since electrophysiological studies revealed that both the defecation and micturition reflexes occurred with very long central delays (45-70 msec). The reflex pathways mediating defecation and micturition in cats with an intact neuraxis were markedly different. Defecation was dependent upon a spinal reflex with unmyelinated (C-fiber) peripheral afferent and efferent limbs. On the other hand, micturition was mediated by a spinobulbospinal pathway with myelinated peripheral afferent (A-fiber) and efferent axons (B-fiber). Transection of the spinal cord at T12-L2 blocked the micturition reflex but only transiently depressed the defecation reflex. In chronic spinal cats the micturition reflex recovered 1-2 weeks after spinalization; however, in these animals bladder-to-bladder micturition reflexes were elicited by C-fiber rather than A-fiber afferents. The C-fiber afferent-evoked reflex was weak or undetectable in animals with an intact neuraxis. Transection of the spinal cord also changed the micturition reflex in neonatal kittens (age 5-28 days). In neonates with an intact neuraxis bladder-to bladder reflexes occurred via a long latency spinobulbospinal pathway (325-430 msec). The long latency is attributable to the slow conduction velocity in immature unmyelinated peripheral and central axons. In chronic spinal kittens (3 7 days after spinalization) the long latency reflex was abolished and a shorter latency (90-150 msec) bladder reflex was unmasked. The emergence of this spinal pathway may reflect axonal sprouting and the formation of new reflex connections within the sacral parasympathetic nucleus. PMID- 6268685 TI - The somato-adrenal medullary reflexes in rats. AB - In chloralose-urethane-anesthetized rats, the effects of somatic stimulation on the adrenal sympathetic efferent nerve activity as well as the adrenal catecholamine secretion were examined. Single shock of the thoracic thirteenth spinal afferent nerve evoked reflex discharges in the adrenal sympathetic efferent nerve. The spinal and supraspinal reflex components evoked by the myelinated and unmyelinated afferent stimulation were identified. The adrenal nerve activity was usually increased reflexly by pinching of the lower chest or upper abdominal skin area in the central nervous system (CNS)-intact animals. Secretion of adrenal epinephrine was noted to be increased reflexly by pinching the lower chest or upper abdominal skin in the central nervous system intact animals. PMID- 6268686 TI - The organization of lumbar preganglionic neurons. AB - The organization of pre- and postganglionic neurons supplying blood vessels of the skin (vasoconstrictor neurons) and of the skeletal muscle (vasoconstrictor neurons), sweat glands (sudomotor neurons) and erector pilimuscles (pilomotor neurons) of the cat's hind limb and tail is discussed. Each sympathetic subsystem has its own, though as yet unknown, central organization which is reflected in the reaction patterns typically seen. The conduction velocities of the pre- and postganglionic axons of each subsystem have their unique distributions. Postganglionic vasoconstrictor neurons supplying skeletal muscle and skin are influenced via cholinergic muscarinic and non-cholinergic synaptic mechanisms from thin, probably unmyelinated, preganglionic axons; postganglionic sudomotor and pilomotor neurons most likely do not receive this synaptic input. A high proportion of preganglionic neurons projecting with their axons onto postganglionic neurons which supply skin and skeletal muscle are silent and do not exhibit reflex activity. Some of these neurons synapse with postganglionic pilomotor, vasodilatator and sudomotor neurons; part of them may also synapse with vasoconstrictor neurons. However, the high proportion of preganglionic neurons without reflex and resting activity which cannot be classified on the basis of functional properties presents a considerable problem in the analysis of the central organization of the sympathetic nervous system. It is concluded that the 4 types of pre- and postganglionic neurons mentioned constitute 4 largely separate channels which transmit information from the spinal cord to the respective target organs. PMID- 6268687 TI - Tonic catecholaminergic inhibition of the spinal somato-sympathetic reflexes originating in the ventrolateral medulla oblongata. AB - In chloralose-anesthetized cats activity of the spinal and supraspinal components of the somato-sympathetic reflex were evoked in the white ramus at T3 by stimulation of the corresponding intercostal nerve. A blockade of all spinal pathways by means of a reversible cold blockade of the spinal cord at C2-C3 produced the following effects: (1) mean arterial blood pressure fell to 30-50 mm Hg and the tonic background activity in the white ramus was markedly reduced; (2) the amplitude of the spinal reflex was significantly increased and the supraspinal reflex was completely abolished; (3) localized cold block of the dorsolateral funiculus produced the same effect as cold block of the whole spinal cord; (4) neither baroreceptor denervation nor midcollicular decerebration altered these effects; and (5) the alpha-adrenoceptor agonist clonidine reduced the increased amplitude of the spinal reflex during cold blockade; this effect was reversed by the alpha-adrenoceptor antagonist yohimbine. Bilateral cold blockade of areas on the ventrolateral surface of the brain stem between the rootlets of the hypoglossal nerve and the trapezoid body caused the same effect on background and reflex activity in the white ramus as did spinal cord blockade. A mapping of the catecholaminergic (CA) neurons in the lower brain stem of the cat by means of the fluorescence method showed CA neurons in the ventrolateral medulla at two levels: (1) one group of neurons in the caudal medulla, which lies ventral and dorsal to the lateral reticular nucleus (corresponding to area A1 in the rat); and (2) a second group found more cranially and located ventrally to the facial nucleus (corresponding to area A5 in the rat). CA nerve terminals in the spinal cord mainly innervate the intermediolateral cell column. From these findings it is concluded that in the anesthetized cat the spinal component of the somato-sympathetic reflex is modulated by a descending tonic inhibition. This inhibition is independent of baroreceptor input. The pathways descend in the dorsolateral funiculus of the spinal cord, and it is suggested that they originate either in the cranial part of area A1 and/or area A5. PMID- 6268688 TI - Interaction between the responses to stimulation of peripheral chemoreceptors and baroreceptors: the importance of chemoreceptor activation of the defence areas. AB - It has been shown recently that in the cat anesthetized with althesin, stimulation of carotid chemoreceptors evokes the autonomic components of the alerting stage of the defence reaction including cholinergic vasodilatation in skeletal muscle. The discrepancy between this result and those of previous experiments on animals anethetized with chloralose or barbiturates may be reconciled when it is realized that these more conventional anesthetics prevent normal transmission through the defence areas. The obvious conclusion, that activation of the defence area is an integral part of the response to peripheral chemoreceptor stimulation indicates that the question of interaction between baro and chemoreceptor responses should be reconsidered, particularly as it is known that the baroreceptor reflex is suppressed when the defence areas are activated by central stimulation. The present paper describes experiments performed on Althesin-anesthetized cats in which carotid baroreceptors were stimulated by inflating a blind sac and carotid chemoreceptors were stimulated by injections of inorganic phosphate solution or saline equilibrated with CO2. The results showed that the baroreceptor reflex may be fully suppressed when the autonomic components of the alerting response were evoked by chemoreceptor stimulation. In some cases however, when the activation of the defence areas was mild, at least as judged by the magnitude of the cholinergic vasodilatation evoked by the chemoreceptor stimulus alone, there appeared to be algebraic summation of the baro- and chemoreceptor response. It is concluded that the extent to which a given chemoreceptor stimulus suppresses the baroreceptor reflex is dependent on its potency as a stimulus to the defence areas. It is suggested that the chemoreceptor input may be more important than hitherto suspected in setting the level of arterial blood pressure. PMID- 6268689 TI - Central adrenoceptors modify hypothalamic thermoregulatory patterns of autonomic activity in conscious rabbits. AB - In conscious rabbits with indwelling intracisternal (i.c.) catheters i.c. injection of noradrenaline (range 20 - 2000 ng) elicited dose-related cutaneous vasoconstriction of the ear skin vessels and reduction in renal sympathetic vasoconstrictor activity (integrated mass discharge). In addition there was shivering and a rise in the animals "core" temperature, so that the injections of noradrenaline mimicked the normal thermoregulatory pattern of cooling. In 5 other rabbits with implanted hypothalamic thermodes we studied the responses of the ear temperature, renal sympathetic nerve activity and respiration rate to hypothalamic heating and cooling. The animals were studied: (i) under control conditions; (ii) after i.c. administration of noradrenaline: (iii) 24 h after 6 hydroxydopamine (6-OHDA) when there is marked depletion of CNS noradrenergic transmitter stores. After the drugs the temperature-response curves were displaced from control in approximately parallel fashion with little change in gain. Noradrenaline elicited shifts that were directionally opposite to those produced by 6-OHDA, suggesting that the changes in thermoregulatory properties were specific effects of the transmitter. Previous studies also suggest that the site of modulation of the thermoregulatory response is at bulbospinal levels, at least as far as the renal sympathetic response was concerned. PMID- 6268690 TI - Solubilized TSH-receptor: its usefulness for the radioligand receptor assay for TSH and TSH-displacing antibody. AB - The usefulness of solubilized TSH-receptor for measuring TSH and TSH-displacing antibodies (TDA) in a radioligand receptor assay (RRA) was investigated. Crude thyroid membranes were solubilized with Triton X-100. A soluble protein fraction was isolated by DEAE-Sephadex A-50 ion-exchange chromatography. The binding of 125I-TSH to the solubilized fraction was studied. It was maximal after 45 min at 37 C, whereas at 4 C a similar binding was observed after at least 17 h. The binding was inhibited by Ca2+ and Mg2+ with concentrations higher than 1 mM and by NaCl in the concentration range 17-150 mM. No inhibition of binding was found with normal serum up to 100 microliter. In contrast, 1.5 microliter of a Graves' disease serum showed significant inhibition. Using the system to measure TSH in serum, as low as 10 microunits TSH could be estimated. Compared to an RRA using thyroid membrane fractions, the sensitivity for TSH in serum as well as for TDA is increased at least tenfold in our system. PMID- 6268691 TI - Binding of solubilized human TSH-receptor protein by peripheral blood lymphocytes of patients with Graves' disease. AB - Peripheral blood lymphocytes (PBL) from patients with hyperthyroidism due to Graves' disease (GD) were investigated for the ability to bind radioiodinated TSH receptor protein as hypothetical autoantigen (ABL). Thyrotropin-displacing antibody (TDA)-positive patients, who relapsed and were investigated shortly after starting antithyroid drug therapy, as well as TDA-positive patients with a first diagnosis of GD, who were investigated before starting therapy, showed significantly increased numbers of ABLs (0.2 +/- 0.17%, p less than 0.01 and 0.15 +/- 0.08%, p less than 0.001, respectively) when compared to controls (0.018 +/- 0.016%). In contrast, TDA - negative patients had no significant increase of ABLs (0.08 +/- 0.09%). Preincubation of PBLs with excess unlabelled antigen and nylon wool filtration of PBLs, reduced the number of ABLs markedly. Blocking of the binding sites on the lymphocytes with anti-Ig serum and blocking of the antigen itself by TSH depleted PBLs almost totally from ABLs. The present data indicate that: i) there are lymphocytes of B-cell characteristics capable of binding TSH receptor; ii) there is a correlation between appearance of ABLs in hyperthyroid GD patients and the detection of TDA in patients' sera; iii) in Hashimoto, toxic nodular goiter and in some normals, a small amount of TSH receptor binding ABLs are detectable. PMID- 6268692 TI - Thyroid hormone binding to plasma membrane preparations: studies in different thyroid states and tissues. AB - Two orders of high-affinity saturable binding sites for L-T4 and L-T3 were evidenced in purified plasma membrane preparations from rat liver (apparent equilibrium dissociation constant KD for T4 congruent to 0.6 and 23 nM, for T3 congruent to 9 and 237 nM) and kidney (KD for T4 congruent to 4 and 127 nM; for T3 congruent to 15 and 270 nM). Differences of statistical significance were only found for the higher affinity T4 binding site. In contrast, no saturable T4 or T3 binding could be detected in spleen plasma membranes. Testis plasma membranes exhibited 2 sets of T4 binding sites but with a lower affinity than in liver and kidney (KD congruent to 28 and 286 nM), and only one set of T3 binding sites (KD congruent to 266 nM). A good correlation was found between the plasmalemma T4 and T3 binding properties of a tissue and its ability to respond to and/or metabolize thyroid hormones. T4 and T3 binding was also examined in liver plasma membranes of rats under various thyroid status; no difference could be detected in either KD or total capacity for both sets of T4 and T3 binding sites when comparing normal with hyper- or hypothyroid rats. The distribution of plasmalemma high affinity specific T4 and T3 binding sites in different tissues suggests that these sites are involved in hormone action, or in the transport of these hormones within the cell. PMID- 6268693 TI - Lack of effect of dexamethasone on the in vivo parathyroid hormone mediated generation of adenosine 3',5'-cyclic monophosphate in rat kidneys. PMID- 6268694 TI - Gonadal and adrenal secretion of dehydroepiandrosterone sulfate in prepubertal and pubertal subjects. AB - The Authors have evaluated the relationship between the secretion of dehydroepiandrosterone sulfate (DHA-S) by the adrenal glands and by the gonads in a group of prepubertal and pubertal subjects ("short normal"), both males and females. In the male subjects of a hCG test and an ACTH test were performed; in the female subjects only the latter test was carried out. The behavior of DHA-S under basal conditions was also assessed in both sexes and related to bone age and chronological age in the prepubertal period and during the early stages of puberty. Plasma levels of DHA-S in both sexes increase progressively with chronological age and bone age. A negative correlation was found between DHA-S and bone delay (expressed in percent relative to chronological age) in prepubertal subjects, both males and females. A significant increase in DHA-S after hCG stimulation was found both in prepubertal and pubertal boys. After ACTH stimulation DHA-S increased significantly in prepubertal and pubertal males and females; throughout the test no difference was found between prepubertal and pubertal subjects nor between male and female subjects. Our data confirm that DHA S is produced both by the adrenals and by the testes. PMID- 6268697 TI - Congenital central ray deficiency in the hand- a survey of 59 cases and subclassification. AB - Eighty-nine hands were studied in 59 patients with central ray deficiency. A subclassification into two subgroups was established based on the clinical and radiological findings-subgroup I: typical type and subgroup II: (atypical type) with type a, syndactylous type, and type b, polydactylous type. In subgroup I, the sequential severity of deficiency ranged from a partial defect of phalanges of the middle finger to a monodigit hand. The central digital elements were fused to adjacent digital rays in subgroup II-type a. Supernumerary bony elements were seen in subgroup II-type b. The close relationship between central ray deficiency, syndactyly, and polydactyly was discussed from the standpoint of development of the hand. The classification of central ray deficiency into the longitudinal deficiency category of the International Classification of Congenital Limb Malformations was recommended. PMID- 6268698 TI - Radial nerve palsy at the elbow following venipuncture-case report. AB - A 29-year-old man sustained a radial nerve lesion when a blood bank technician attempted to cannulate the cephalic vein. Severe pain in the hand and fingers led to removal of the 16-gauge needle. A complete motor and sensory deficit occurred below the elbow. Electrical testing confirmed the neurologic lesion. Complete recovery took 3 months. PMID- 6268696 TI - [Virilising luteoma during pregnancy. A case report and a review of the literature (author's transl)]. AB - Luteoma in pregnancy is a rare tumour (about 100 published cases) and it is rarely associated with signs of virilisation (28 published cases). A visiting luteoma in pregnancy in primigravid woman of 27 years of age is reported and compared with other cases in the literature. A study of the androgen secretions before and after pregnancy and especially the levels of androgens in the peripheral blood, the ovarian vein and in the tumour ware carried out so that metabolic pathways of the production of the androgens could be worked out. The particular circumstances of the unexpected appearance of this luteoma during an H.C.G. stimulation test (Human Chorionic Gonadotrophin) gives an opportunity to define the role of this hormone in its occurrence. Finally, a review of the literature makes it possible to draw up a history of the usual behaviour of these virilising luteomas in pregnancy: they usually show up in the second trimester of pregnancy, and the overriding role is played by testosterone with virilisation of female fetuses. PMID- 6268699 TI - Nocardia infection of the hand-case report. PMID- 6268700 TI - Earlier diagnosis of gastric infiltrating carcinoma (scirrhous cancer). AB - We approached the early diagnosis of gastric infiltrating carcinoma, scirrhous cancer, by a retrospective study of 19 patients, together with a prospective study of a single patient, by reexamination and follow-up of gastric roentgenographs and endoscopic films. This study suggests that an early feature of this type of gastric cancer might be IIc- or III + IIc-like depression in the body of the stomach, probably in the fundic region of the stomach. A shallow depression or a slight stiffness of the gastric wall may be one of the earliest roentgenographic or endoscopic findings helpful in early detection of this disease. PMID- 6268695 TI - Behavioral effects of ACTH and MSH peptides. PMID- 6268701 TI - Association of squamous carcinoma of the esophagus with a synchronous primary hepatocellular carcinoma. AB - We have seen a patient with a squamous carcinoma of the esophagus along with hepatocellular carcinoma. Though the simultaneous occurrence of these tumors is rare, we propose that their development may be more than a chance occurrence. Since many chemical carcinogens which promote esophageal cancers in experimental animals also promote hepatic malignancies, it is possible that dietary nitrosamines in man, causally implicated in esophageal carcinoma, may also sometimes induce hepatic carcinoma in the same patient. PMID- 6268702 TI - Variation in spermatozoal levels of phosphoglycerate kinase-2 in mice. AB - Litter size differences exist between inbred strains of mice with high and low spermatozoal phosphoglycerate kinase-2 activity, but an examination of these two variables in recombinant inbred lines between the two strains suggest that the variables are not related. An examination of spermatozoal cAMP concentrations in these recombinant inbred lines demonstrated no correlation with litter size. Furthermore, spermatozoal cAMP concentrations were demonstrated to be under multigenic control. PMID- 6268703 TI - Inheritance of delta 9-tetrahydrocannabinol seizure susceptibility in rabbits. AB - Delta 9-Tetrahydrocannabinol (THC), the major psychoactive ingredient of marijuana, causes nonfatal convulsions in rabbits of a closed colony of New Zealand White rabbits (Uaz: NZW). The convulsive phenotype appears to be associated with homozygous expression of a single autosomal recessive gene with full penetrance. We propose the symbol thc for the gene responsible for this condition. We also propose that this closed colony of New Zealand White rabbits at the University of Arizona, in which the thc gene is segragating, be designated Uaz:NZW-thc. PMID- 6268704 TI - Requirements for the establishment of high-titered human monoclonal antibodies against tetanus toxoid using the Epstein-Barr virus technique. PMID- 6268705 TI - Adherent spleen cells from mice acutely infected with cytomegalovirus suppress the primary antibody response in vitro. AB - In the present study, we have demonstrated that the hemolytic plaque response of spleen cells from mice acutely infected with murine cytomegalovirus (MCMV) is suppressed in vitro. Mishell-Dutton cultures established with spleen cells from C57BL/6 mice infected 4 days earlier with 4.2 X 10(3) plaque-forming units of MCMV were found to produce significantly fewer direct plaques upon stimulation with sheep red blood cells than corresponding control cultures. Suppression could not be attributed to a generalized lytic destruction of spleen cells, nor was it produced by addition of virus directly to uninfected spleen cell cultures. However, in cultures containing various mixtures of cells from control and infected mice, the direct plaque response was markedly below the predicted response, suggesting that the uninfected cells were actively suppressed by cells from infected mice. Suppression was dependent on the presence of intact spleen cells, since it was not found in the presence of lysed cells. The capacity of spleen cells from infected mice to mediate suppression was demonstrated in the plastic-adherent subpopulation. Treatment of these cells with anti-thymocyte serum (ATS) and complement did not abolish the capacity to suppress the immune response. Thus, adherent ATS-resistant cells from the spleens of mice acutely infected with MCMV, rather than virus alone, have the capacity to actively suppress the hemolytic plaque response in vitro. PMID- 6268706 TI - A monoclonal antibody inhibiting human neutrophil chemotaxis and degranulation. AB - The hybridoma technique of Kohler and Milstein was used to raise a monoclonal antibody against human neutrophils it has been found to inhibit neutrophil chemotaxis and degranulation. The antibody has been termed NCD 1. Incubation of 12 micrograms of NCD 1 with neutrophils (2 X 10(6)), followed by incubation with cytochalasin B and stimulation with either C5a, fMet-Leu-Phe, or soluble aggregated immunoglobulin, resulted in the inhibition of lysosomal enzyme release. The inhibition was not cytochalasin B dependent, since lysosomal enzyme release induced by opsonized zymosan or opsonized sheep erythrocytes was also inhibited, even in the absence of cytochalasin B. NCD 1 had no affect on enzyme release induced by the calcium ionophore A23138 or by phorbol myristate acetate. The antibody also inhibited neutrophil chemotaxis to zymosan-activated plasma and fMet-Leu-Phe. By contrast, superoxide production stimulated by phorbol myristate acetate, opsonized zymosan, or fMet-Leu-Phe was not affected by NCD 1. Similarly, uptake of 51Cr-labeled opsonized sheep erythrocytes into neutrophils was resistant to the effects of the antibody. NCD 1 Fab fragments did not inhibit lysosomal enzyme release or chemotaxis, althugh binding to the neutrophil surface was demonstrated by immunofluorescence. NCD 1 F(ab')2 fragments behaved analogously to the whole antibody. Binding of both fMet-Leu-[3H]Phe or 125I soluble aggregated immunoglobulin to the cells was not inhibited by the antibody, which implied that NCD 1 was inhibiting some post-ligand binding event. PMID- 6268707 TI - Functions of human monocyte and lymphocyte subsets obtained by countercurrent centrifugal elutriation: differing functional capacities of human monocyte subsets. AB - Two monocyte subsets from the peripheral blood of healthy humans were isolated by countercurrent centrifugal elutriation (CCE), and their functional heterogeneity was assessed. Cell volume of the smaller monocyte population was (332 +/- 32 mu 3), compared with the larger monocytes (380 +/- 30 mu 3). Superoxide release by large monocytes exposed to opsonized zymosan was 1.5-fold more active than those of small monocytes. Furthermore, the production of colony-stimulating factor (CSF) and myeloperoxidase activity by the larger monocytes was 2-fold and 1.4 fold greater than that of small monocytes, respectively. Thus, CCE provides a useful means to isolate 2 subsets of monocytes with similar functional properties but quantitatively different activities. This suggests that the 2 subsets may be closely related in their developmental spectrum. PMID- 6268708 TI - Effects of prostaglandin D2 and theophylline on rat serosal mast cells: discordance between increased cellular levels of cyclic AMP and activation of cyclic AMP-dependent protein kinase. AB - Previous studies have shown that perturbation of the mast cell IgE-Fc receptor activates adenylate cyclase so as to raise cellular levels of cyclic AMP and to activate cyclic AMP-dependent protein kinase. Theophylline, an inhibitor of cytoplasmic cyclic nucleotide phosphodiesterase, raises cellular cyclic AMP levels, activates Type I and Type II cytoplasmic cyclic AMP-dependent protein kinase isoenzymes, and inhibits immunologic mediator release in a dose-dependent fashion. Since the EC50 values for each of these effects are similar (8 to 9.5 mM), it seems likely that a relationship exists between the activation of cyclic AMP-dependent protein kinase and the inhibition of mediator release. Such inhibition could be due to either to the uncovering of an inhibitory protein by phosphorylation or to the depletion of cyclic AMP-dependent protein kinase holoenzyme, which is essential for productive IgE-Fc receptor-induced activation secretion coupling. PGD2, which also raises mast cell cyclic AMP levels in a dose dependent fashion and interacts synergistically with theophylline in this regard, fails to suppress mediator release alone or to add to the inhibitory effect of theophylline. The finding that PGD2 also fails to activate cyclic AMP-dependent protein kinase suggests that the adenylate cyclase stimulated by this agonist is not linked to the mast cell activation-secretion response. PMID- 6268709 TI - Assessment of antibody mediated cytolysis of adult cardiocytes isolated by centrifugation in a continuous gradient of Percoll in patients with acute myocarditis. AB - Principal objections to conventional cytotoxicity assays in cardiac disease with myocytes as target cells are the use of fetal or neonatal myocardium, the cell membrane of which does not express all antigenic determinants, and the use of trypsin as enzyme for isolation of the cells, since this alters the myolemmal membrane considerably. An improved and rapid procedure for the isolation of intact adult cardiocytes with collaggenase was developed. by means of a performed continuous self-generating silica sol and gradient centrifugation average enrichment of 81% vital myocytes was achieved by a single isopycnic procedure. The yield was improved to 94 +/- 3% vital cells by identical second centrifugation. Cardiocytes isolated by this method were used as target cells in an assay measuring the cytolytic activity of antibodies in the presence of complement: sera of patients suffering from acute viral myocarditis (Coxsackie B- and influenza-virus) with complement fixing antisacrolemmal antibodies (ASA) of the IgG- and IgM-type showed significant cardiocytolysis. ASA are postulated to play a role in the pathogenesis of acute Coxsackie B- and influenza-virus myocarditis. PMID- 6268710 TI - Heterologous tumor growth patterns induced in related MHC-defined chicken lines by separate isolates of an avian sarcoma virus strain. AB - Different patterns of tumour growth resulted from inoculation of separate isolates of the Subgroup C Bratislava 77 strain (B77) of Avian Sarcoma Virus (ASV) into three closely-related inbred lines of chickens. The major genetic difference between these chicken lines is that each is homozygous for a different MHC haplotype. Since for one of the viral isolates, resistance to progressive tumour growth has been shown to be controlled by MHC-linked genes, the data presented here suggest that MHC-controlled tumour rejection operates on viral or cellular determinants different from those which define classical viral group of subgroup specificity. PMID- 6268711 TI - Separation of newborn rat epidermal cells on discontinuous isokinetic gradients of PERCOLL. AB - A one-step procedure has been developed for the separation of epidermal cells using PERCOLL (a new colloidal silica medium of low viscosity, osmolarity, and toxicity) for density gradient centrifugation. Newborn rat epidermal cells were dispersed with trypsin-EDTA and separated into 4 fractions in discontinuous isokinetic gradients. The cell fractions were characterized by their appearance in photomicrographs and their distribution by number and size. Preferential incorporation of 3H-thymidine and 14C-glycine, by basal and granular cells respectively, confirmed the identification of cell types. The basal cells, which were collected in the densest fraction (1.090), were the most homogeneous population with a mean diameter between 7-8 mum and showed 98% viability. The granular cells predominated in the least dense fraction (1.023). The intermediate fractions contained spinous cells admixed with the other cell types. PMID- 6268712 TI - The effects of alpha and beta adrenergic agonists and cyclic adenosine 3':5' monophosphate on epidermal metabolism. AB - Continuously regenerating stratified squamous epithelia form an interesting model for examining mechanisms controlling the balance between rates of cell formation and cell maturation and death. In vitro assays of rates of glycolysis and amino acid incorporation of epidermal sheets free from dermal contamination were used to examine rates of metabolism in both normal and hyperplastic epidermis after treatment with various adrenergic agonists and cAMP. Epinephrine and isoproterenol over the concentration range of 1 x 10(-9) to 1 x 10(-5) M depressed the rates of glycolysis and amino acid incorporation in normal epidermis. Dibutyryl cyclic AMP produced a 73 to 78% depression in metabolic activity and its action was enhanced by the addition of theophylline. The alpha adrenergic agonist norepinephrine produced similar reductions. When epidermal samples were treated with hexadecane to induce a mild hyperplasia, depressant effects of isoproterenol and epinephrine were lost, but dibutyryl cyclic AMP and norepinephrine still reduced metabolic activity. The results suggest that adrenergic agents and their putative second messenger cAMP cause reductions in epidermal metabolic activity, an effect similar to their effects on cell proliferation, and that increased rates of proliferation are associated with loss of beta adrenergic responsiveness of the epidermis. PMID- 6268713 TI - A prospective study of rotavirus infection in infants and young children. AB - Diarrhea in neonates, followed as a cohort, and their families was studied prospectively. The families were followed for an average of 16.3 months. Stool and serum specimens were obtained at least every three months. Stool specimens were examined for viruses by electron microscopy and cultured for enteropathogens, and serum specimens were tested for antibodies to rotavirus and Norwalk virus. During the study, 237 episodes of gastroenteritis were observed in 104 infants and their 62 siblings. Rotavirus, detected 82 times in 72 children, was by far the most common enteropathogen. It was associated with gastrointestinal symptoms in 72% (with diarrhea in 65%). Rotavirus diarrhea occurred mostly in winter months and was significantly more frequently associated with respiratory symptoms than were diarrheas with other etiologies. Rotavirus infection was uncommon in the first six months of life, but by two years of age, 62% of the infants had had at least one infection. Neither breast feeding nor the presence of antibody to rotavirus in cord blood appeared to be protective. PMID- 6268714 TI - A mouse model of dilated-type cardiomyopathy due to coxsackievirus B3. AB - Myocardial scarring was induced in 111 mice (group 3) inoculated at 14 days of age with coxsackievirus B3 and forced to swim for 30 min daily during the initial nine days of infection. The animals were observed until age 15 months. Control animals included mice infected but not forced to swim (group 2), neither infected nor forced to swim (group 1), and not infected but forced to swim (group 4). The cumulative mortality was 45% among mice in group 3 but was significantly lower in the control animals. At 15 months, mice in group 3 showed heavy deposits of calcium in the injured myocardium, atrial hypertrophy with thrombi, and myocardial fiber disintegration with replacement by fibrous scar. Mononuclear infiltration was no longer present. Pathologic changes were concentrated in the left ventricle, interventricular septum, and atrioventricular junction. Titers of type-specific neutralizing antibodies had declined to one-fifth the level present at one month. These findings represent a model of dilated-type cardiomyopathy. PMID- 6268715 TI - Efficacy of ampicillin plus a beta-lactamase inhibitor (CP-45,899) in experimental endocarditis due to Staphylococcus aureus. AB - The efficacy of combined therapy with ampicillin and a beta-lactamase inhibitor, CP-45,899, for experimental endocarditis due to Staphylococcus aureus was evaluated. Three strains of beta-lactamase-producing S. aureus were used, and intramuscular doses of antibiotics were selected to produce serum levels in rabbits similar to those expected in humans. Sera from animals treated with ampicillin plus CP-45,899, but not from those treated with nafcillin plus gentamicin, had bactericidal activity against two nafcillin-resistant strains of S. aureus at 1 hr. The combination of ampicillin plus CP-45,899 was as effective as nafcillin in treatment of endocarditis due to one nafcillin-sensitive strain and was superior to nafcillin against two nafcillin-resistant strains (P less than 0.001). In a short-term treatment experiment using the nafcillin-sensitive strain, ampicillin plus CP-45,899 sterilized vegetations as rapidly as nafcillin plus gentamicin. Thus, ampicillin plus a beta-lactamase inhibitor may be effective treatment for bacteremic infections due to S. aureus, even when the strain is nafcillin-resistant. PMID- 6268716 TI - Fibroblast stimulation in schistosomiasis. I. Stimulation in vitro of fibroblasts by soluble products of egg granulomas. AB - To gain further understanding of the pathogenesis of hepatic fibrosis in schistosomiasis, the interaction between egg granulomas and fibroblasts was investigated in an in vitro model. Egg granulomas isolated from livers of mice infected with Schistosoma mansoni or Schistosoma japonicum and cultured in vitro released a nondialyzable substance which stimulated proliferation in resting dermal fibroblasts. The release of the fibroblast-stimulating substance remained relatively constant during the first 48 hr of incubation with granulomas, during which time granulomas remained metabolically active in vitro. A dialyzable molecule(s) in granulomas supernatants interfered with fibroblast uptake of [3H]thymidine in vitro but did not inhibit cellular division. Granulomas supernatants also stimulated fibroblast secretion of prostaglandin E2 and caused an elevation in intracellular levels of cyclic adenosine monophosphate. PMID- 6268717 TI - [The elimination of nonspecific reaction in ELISA --for the application of routine serological test on varicella zoster, measles and rubella virus (author's transl)]. PMID- 6268718 TI - [beta 1, beta 2-effects of ritodrine in pregnant animal experiments (author's transl)]. AB - beta 2-Stimulant are at present the most effective tocolytic agents. The purpose of this paper is to outline the beta 1-, beta 2-effects of ritodrine in animal experiments. 1) In the pregnant rat uterus at term, ritodrine and terbutaline showed the potent effect. The c-GMP level in the bath medium was significantly decreased by the administration of ritodrine, while the c-AMP levels was significantly increased. 2) When the changes in the maternal serum c-AMP and c GMP levels after the administration of ritodrine were examined, these results coincided with those obtained experiments in vitro. But decreased in c-AMP and c GMP levels by administering beta-blocker. The c-AMP and c-GMP levels of placenta, liver, uterus and fetus showed similar patterns, especially c-AMP in the uterine and fetal tissues increased when ritodrine was administered. 3) The administration of ritodrine and terbutaline at the last trimester of pregnancy led to the increased, showing dose-response relationship, in the heart rate of mother and fetus in rabbits. 4) The effect of ritodrine on fetal and neonatal serum glucose concentrations was examined in rats. Sustained hypoglycemia was observed in fetus and neonate delivered within 18 hours of the termination of administration (ritodrine, 10-20 mg, sc). PMID- 6268719 TI - [Biological characterization including sensitivity to mitomycin C of cultured human ovarian cancers (author's transl)]. AB - The present study first dealt with characterization of two cell lines, Kuramochi and CKS, established from human ovarian cancer. Secondary, the quantitative analyses of sensitivity of the cell lines to Mitomycin C was reported. The two cell lines showed typically epithelial features in vitro. Kuramochi cells, derived from undifferentiated carcinoma, had microvilli on the cell surface, cell continuity with the relative developed junctional complex, but no secretary granules and vesicles. The chromosomal analysis revealed the hyperdiploid modal number of 50. The population doubling time was about 26 hours. CKS cells, derived from serous cystadenocarcinoma, had secretary vesicles, microvilli, but no developed junctional complex. The chromosomal analysis reveals the hypodiploid modal number of 37. The population doubling time was about 34 hours. Biochemical markers of alpha-fetoprotein, human chorionic gonadotropin and carcinoembryonic antigen were not detected in both cell lines. 90% lethal dose of 2-hr-treatment with Mitomycin C was 0.42 microgram/ml in Kuramochi cell line and 1.13 microgram/ml in CKS cell line. These values were higher than the one of the control cell line, KATO-III, derived from signet-ring cell carcinoma of stomach. Ovarian cancers were suggested resistant to Mitomycin C. PMID- 6268720 TI - [An angiographic study of congenital hand anomalies (author's transl)]. AB - Accurate knowledge of the arterial variations of the anomalous hand is of considerable practical importance not only in the process of reconstructive surgery in hand anomalies but also in the consideration of the classification and the developmental stage of these defects. Between 1970 and 1980, we have performed an angiography on 102 anomalous hands of 97 patients at the Department of Orthopaedic Surgery, Nagoya University Branch Hospital. They consist of 28 cases of polydactyly, 25 of syndactyly, 14 of cleft hand, 13 of radial ray deficiency, 6 of ulnar ray deficiency, 6 of congenital constriction band syndrome, 5 of brachysyndactyly, 3 of macrodactyly and 1 each of monodactyly and aberrant muscle of the forearm. High origin of the radial artery was encountered in 11 out of 95 hands (11.6 per cent). In 5 out of 11 hands, an incomplete volar arch was found. The median artery entered into the formation of the superficial volar arch in about 20 per cent of cases. It occurred most frequently in radial ray deficiency (Table 1). An unusual division and course of the artery in the forearm occurred in 5 hands. The developmental disorders of the radial artery were encountered in 19 of the 102 hands (18.6 per cent). Especially, they were observed frequently in radial ray deficiency, and represented an occurrence in 84.6 per cent of these deficits (Table 2). The superficial volar arch was absent in about 25 per cent of cases. This arterial pattern was seen frequently in cleft hand and syndactyly (Table 3). In 30 of the 39 cases of syndactylism, the common digital artery bifurcated into the proper digital artery much further distally than normal. The digital arterial patterns of the duplicated thumb could be divided into 4 types (Fig. 3). The arterial patterns of cleft hand were quite different from those with radial ray deficiency, but were rather similar to those of syndactyly. The arterial patterns of ulnar ray deficiency tended to fall into two groups: those with the developmental disorders of the radial artery and those without them. PMID- 6268721 TI - [Clinical-pharmacological effects of angiotensin II upon intra-arterial infusion cancer chemotherapy (author's transl)]. PMID- 6268722 TI - Unsuspected malignant tumors. PMID- 6268723 TI - Regulation of rat liver microsomal cholesterol 7 alpha-hydroxylase: reversible inactivation by ATP + Mg2+ and a cytosolic activator. AB - Modulation of cholesterol 7 alpha-hydroxylase catalytic activity by adenine nucleotides was studied in rat liver microsomal preparations. Inactivation of cholesterol 7 alpha-hydroxylase showed specific requirements of ATP and ADP. AMP and cyclic AMP were stimulatory and cyclic AMP had no effect in the ATP inactivation. The inactivation reactions by ATP were dependent on Mg2+ ions, a cytosolic factor, and time. Ca2+ ions were less effective whereas Mn2+ ions were highly inhibitory to hydroxylase activity. The inactivation could be reversed in a time-dependent reaction requiring a cytosolic activator that was precipitable by ammonium sulphate of saturation up to 65%. The current data suggest that cholesterol 7 alpha-hydroxylase can exist in two catalytic forms that are reversible. PMID- 6268724 TI - Lipid composition of Balb/c3T3, SV3T3, and Concanavalin A-selected revertant cells grown in media containing lipid-depleted serum. AB - The effects of growth in media supplemented with lipid-depleted fetal calf serum (LDS-media) on morphology, saturation density, and lipid composition were studied in Balb/c3T3, SV3T3, and Concanavalin A selected SV3T3 revertant cells (SV3T3 Rev cells). Cells grown in media containing complete fetal calf serum (FCS-medium) or reconstituted FCS (RS-medium) were used as controls. Growth in LDS-media reduced saturation densities of both SV3T3 and SV3T3 Rev cells while it affected only slightly the saturation density of normal parental cells. Similar inhibitory effects on growth were also induced by exposure of RS-medium. Growth in LDS medium did not change the typical morphology of the three cell lines. 3T3, SV3T3, and SV3T3 Rev cells grown in LDS-medium showed an accumulation of triacylglycerols and free fatty acids together with a reduction of free cholesterol. All these changes were also present, however, in cells grown in these changes were also present, however, in cells grown in RS-Medium. Growth in LDS-medium induced an increase of 16:1 and 18:1, a decrease of 20:4, and an accumulation of 20:3 (n-9) in phosphatidylethanolamine, phosphatidylcholine, and phosphatidylinositol + phosphatidylserine of 3T3 cells. By contrast, only a slight accumulation of 20:3 (n-9) accompanied by a moderate increase of monoenoic acids was found in the phospholipids of SV3T3 cells grown in LDS-medium. SV3T3 Rev cells grown in LDS-medium showed changes in phospholipid fatty acids composition similar to those found in SV3T3 cells grown under the same conditions. PMID- 6268725 TI - A new solvent system for the separation of neutral glycosphingolipids. AB - A solvent system and a column for high performance liquid chromatography for the separation of glycosphingolipids without derivatization is described. A column pakced with porous silica gel (latrobeads) and eluted with a mixture of isopropanol-hexane-water with increasing water content and decreasing hexane content was used. Glycosphingolipids with mono- to dodeca- or tetrakaidecasaccharides were separated within 60 min and the separation pattern was highly reproducible. The method was applied for preparative separation of highly complex glycolipids with blood group activity. PMID- 6268726 TI - Cellular retinoid-binding proteins in reginerating rat liver: demonstration of a novel cellular retinoid-binding protein. AB - Changes in the levels of liver cellular aetinol- and retinoic acid-binding proteins were studied after partial (about 70%) hepatectomy for 14 days in the rat. It was found that a novel binding protein designated F-type appears transiently in liver cytosol 3 days after the operation. The appearance of this protein coincides with the peak level of the alpha 1-fetoproteain. In contrast, cellular retinoic acid-binding protein was detected only the first day after hepatectomy, whereas no significant change was observed in the level of the cellular retinol-binding protein during the entire observation period. [3H]Retinol or [3H]retinoic acid complexed with serum retinol-binding protein injected intravenously into vitamin A-deficient rats 1 day after the hepatectomy was recovered 5 min or 20 min later bound specifically to cellular retinol- or retinoic acid-binding protein, respectively. The results presented here strongly suggest that each of the three cellular retinoid-binding proteins plays a distinct role in cell proliferation and differentiation. PMID- 6268727 TI - Mechanism of the age-related decrease of epinephrine-stimulated lipolysis in isolated rat adipocytes: beta-adrenergic receptor binding, adenylate cyclase activity, and cyclic AMP accumulation. AB - beta-adrenergic binding ([3H]dihydroalprenolol), adenylate cyclase activity, and cAMP accumulation were measured in adipocytes to investigate whether the mechanism of decreased hormone-sensitive lipolytic response with age was mediated through membrane-associated events. The dose of epinephrine required for half maximal stimulation of glycerol release (ED50) was significantly lower in 2-month old rats (0.8 +/- 0.2 microM)than in matur (6- and 12-month-old) rats (5.2 +/- 1.5 and 6.2 +/- 1.5 microM, respectively). In 24-month-old rats the ED50 (0.7 +/- 0.2 microM) was less than in mature rats. maximum rates of hormone-stimulated glycerol release (per 10(6) cells) was highest in the two mature groups and decreased by 50% in the old rats (P less than 0.01). Lipolytic changes were independent of cell size. beta-adreanergic raeceptor number (50-90 thousand sites/call) and affinity (KD 4-5 nM) were the same in each age group. ED50 and maximum level of hormone-stimulated adenylatae cyclase activity did not change with age. The ED50 of cAMP accumulation of young rats was 3 +/- 5 microM compared with 24 +/- 4 and 25 +/- 5 microM in 6- and 12-month-old rats, respectively. In old rats, the ED50 of cAMP accumulation was 2 +/- 1 microM (P less than 0.001 compared with mature rats). Maximally stimulated cAMP levels were the same in old and mature animals. Phosphodiesterase activity in the presence and absence of 10( 5) M isoproterenol did not change with age. The results suggest that age-related decrease of epinephrine-sensitive lipolysis in old rats may be due to alterations of the lipolytic pathway distal to the receptor-adenylate cyclase complex and the generation of cyclic AMP. PMID- 6268729 TI - Rotavirus infection in Thai people: a preliminary study. PMID- 6268728 TI - Chemical analysis of glycosaminoglycans inhibiting DNA synthesis. AB - Sulfated glycosaminoglycans having inhibitory activity in cellular and subcellular systems were found in some tumor tissues from humans. These glycosaminoglycans inhibited more efficiently DNA synthesis of virus transformed cells (SV40-WIRL-3 cells) than their parent normal cells (WIRL-3 cells). Sulfated glycosaminoglycans found in normal human and non-tumor tissues did not have as high an inhibitory activity on DNA synthesis by cells used in this investigation as those from some human tumor tissues. The former did not inhibit as effectively DNA synthesis by virus transformed cells, as DNA synthesis by their normal parent cells. The monosaccharide composition of these sulfated glycosaminoglycans showed N-acetyl glucosamine (Glu-NAc) as a main monosaccharide, and xylose (Xyl), glucose (Glu), galactose (Gal), hyaluronic acid (Hu-A) as minor monosaccharides. N-acetyl galactosamine was not detected. PMID- 6268730 TI - Mitochondrial number, cytochrome oxidase and succinic dehydrogenase activity in Xenopus laevis oocytes. AB - An estimate has been made of the numbers of mitochondria in the mitochondrial cloud (Balbiani body) of Xenopus laevis oocytes ranging in size from 50 to 250 micrometers. The mitochondrial number is expressed in terms of a 'standard' organelle measuring 2 micrometers in length and 0.2 micrometer in diameter and is derived by measurements on electron micrographs of sections through the cloud. It is found that the amount of mitochondrial material rises very rapidly as the oocyte grows in size. At the time the cloud disperses, in oocytes of about 300 micrometers in diameter, it is estimated that there are the equivalent of over 500 000 mitochondria in each cell. The rate of increase is very similar to the rate of accumulation of mitochondrial DNA during the same period of growth. Using a polarographic technique the specific activity of cytochrome oxidase and succinic dehydrogenase was determined in mitochondrial fractions isolated from oocytes over a size range of 80-1200 micrometers in diameter. Although the specific activity of succinic dehydrogenase remains constant that of cytochrome oxidase falls sharply during the period when the mitochondria are replicating rapidly, i.e. up to about 300 micrometer diameter. In larger oocytes the specific activity of enzymes appears to remain constant but increasing contamination of the isolated mitochondrial fraction does not allow conclusions to be drawn from the enzyme loading of the mitochondria once they have dispersed from the cloud. The results are discussed in relation to the possibility that mitochondrial replication preceeds, or at least outpaces, mitochondrial differentiation during the course of oogenesis. PMID- 6268731 TI - A cell surface antigen of the mouse related to xenotropic MuLv defined by naturally occurring antibody and monoclonal antibody. Relation to Gix G(rada1), G(aksl2) systems of MuLV-related antigens. AB - A new cell surface antigen of the mouse related to xenotropic murine leukemia virus (MuLV) is described. The antigen, designated G(erld), is defined by cytotoxic tests with the B6-x-ray-induced ERLD and naturally occurring antibody. G(erld) is distinct from all previously defined cell surface antigens. Monoclonal antibody with the same specificity has been developed. Inbred mouse strains are classified as G(erld)+ or G(erld)- according to the presence of absence of the antigen on lymphoid cells. G(erld)+ strains differ with regard to quantitative expression of G(erld) on normal thymocytes. The emergence of G(erld)+ tumors in G(erld)- strains indicates the presence of genes coding for the antigen even in strains not normally expressing the antigen. G(erld) has the characteristic of a differentiation antigen in normal mice. In G(erld)+ strains, high levels of the antigen are found on thymocytes with lower levels being detected on cells of spleen, lymph nodes and bone marrow. No G(erld) was detected in brain or kidney or on erythrocytes. The segregation ratios for G(erld) expression on thymocytes in backcross and F2 mice of crosses between G(erld)+ (B6, 129, and B6-Gix+) and G(erld)- (BALB/c) strains suggest that G(erld) expression is controlled by a single locus in B6, by two unlinked loci in 129, and by three unlinked loci in B6 Gix+ mice. Induction of the antigen by MuLV infection of permissive cells in vitro indicates that G(erld) is closely related to xenotropic and dualtropic MuLV; all xenotropic and dualtropic MuLV tested induced the antigen, whereas the majority of ecotropic and the two amphotropic MuLV failed to do so. As dualtropic MuLV are thought to be recombinants between ecotropic and xenotropic MuLV sequences, G(erld) coding by dualtropic MuLV may signify the contribution of the xenotropic part in the recombinational event. Serological and biochemical characterization indicates that G(erld) is related to the gp 70 component of the MuLV envelope. The relation of G(erld) to the previously defined gp 70-related cell surface antigens (Gix, G(rada), and G(aksl2) is discussed, particularly with regard to their characteristics as differentiation antigens, the genetic origin of dualtropic MuLV, and the leukemogenicity of MuLV. PMID- 6268732 TI - Characteristics of Epstein-Barr virus activation of human B lymphocytes. AB - Epstein-Barr virus (EBV) will infect at least every third cell if exposed in vitro to an extensively purified B cell population from human peripheral blood. About 10% of such infected cells will be driven into immunoglobulin synthesis and secretion, as judged by the indirect protein A plaque assay. The appearance of EB nuclear antigen, de novo DNA synthesis, and immunoglobulin secretion are linked phenomena accompanying infection as judged by viral dilution experiments, which yield kinetics of a one-hit order. Induction of immunoglobulin secretion in B cells by EBV requires de novo synthesis of DNA, and consequently, nontransforming EBV (P3HR1) will not induce immunoglobulin secretion and will also specifically block such induction from subsequently added EBV. The termination of immunoglobulin induction by EBV in short-term cultures appears to be T cell dependent. PMID- 6268734 TI - A simultaneous radioimmunoassay for aldosterone and its precursors: human plasma levels following the inhibition of converting enzyme, before and after blockade of prostaglandin biosynthesis. AB - Plasma aldosterone, 18-hydroxycorticosterone, corticosterone, 18 hydroxydeoxycorticosterone, and deoxycorticosterone were determined in 15 healthy male volunteers (34 +/- 2 years) following the inhibition of converting enzyme with captopril (SQ 14.225), either with or without indomethacin pretreatment. These studies were performed with the aid of a radioimmunological method for the simultaneous determination of the steroids from 1.0 ml of plasma. The procedure involves one extraction and one chromatographic step. Highly sensitive and specific rabbit antisera were raised for all steroids. Precision and accuracy are shown to be equivalent to those of single steroid radioimmunoassays. Without indomethacin pretreatment a constant and significant fall in aldosterone and 18 hydroxycorticosterone plasma levels was obtained after captopril. 18 Hydroxydeoxycorticosterone and corticosterone did not change after inhibition of converting enzyme. Under indomethacin pretreatment all basal steroid levels were significantly reduced. After captopril, aldosterone did not change and 18 hydroxycorticosterone showed a smaller decrease than without indomethacin. 18 Hydroxydeoxycorticosterone and corticosterone increased significantly 1 1/2 hour after captopril. We conclude that indomethacin significantly reduces basal mineralocorticoid production of adrenal zona glomerulosa and fasciculata. Furthermore, the effect of captopril on aldosterone and 18-hydroxycorticosterone is abolished or diminished by inhibition of prostaglandin biosynthesis, but indomethacin does not prevent an augmented secretion of 18 hydroxydeoxycorticosterone and corticosterone. PMID- 6268735 TI - Effects of deuterium oxide on the rate and dissociation constants for saxitoxin and tetrodotoxin action. Voltage-clamp studies on frog myelinated nerve. AB - The actions of tetrodotoxin (TTX) and saxitoxin (STX) in normal water and in deuterium oxide (D2O) have been studied in frog myelinated nerve. Substitution of D2O for H2O in normal Ringer's solution has no effect on the potency of TTX in blocking action potentials but increases the potency of STX by approximately 50%. Under voltage clamp, the steady-state inhibition of sodium currents by 1 nM STX is doubled in D2O as a result of a halving of the rate of dissociation of STX from the sodium channel; the rate of block by STX is not measurably changed by D2O. Neither steady-state inhibition nor the on- or off-rate constants of TTX are changed by D2O substitution. The isotopic effects on STX binding are observed less than 10 min after the toxin has been added to D2O, thus eliminating the possibility that slow-exchange (t 1/2 greater than 10 h) hydrogen-binding sites on STX are involved. The results are consistent with a hypothesis that attributes receptor-toxin stabilization to isotopic changes of hydrogen bonding; this interpretation suggests that hydrogen bonds contribute more to the binding of STX than to that of TTX at the sodium channel. PMID- 6268733 TI - Friend murine leukemia virus-induced leukemia is associated with the formation of mink cell focus-inducing viruses and is blocked in mice expressing endogenous mink cell focus-inducing xenotropic viral envelope genes. AB - In these studies, we have shown data that are consistent with the hypothesis that mink cell focus-inducing viruses (MCF) play an important role in the generation of an erythroproliferative disease developing after injection of certain strains of newborn mice with ecotropic Friend murine leukemia virus (F-MuLV). Resistance to this disease is correlated with the endogenous expression of an MCF/xenotropic virus-gp70-related protein that may interfere with the replication or spread of MCF viruses. These ideas are supported by the following observations: (a) after infection with F-MuLV, only 6/13 strains of mice-developed disease, and studies with crosses between susceptible and resistant strains indicated that resistance was dominant. Although F-MuLV was shown to replicate equally well in all strains tested, viruses coding for MCF-specific viral envelope proteins could be detected only in the spleens of mice from strains that were resistant to F-MuLV-induced disease and not in the spleens of mice from strains that were resistant to F-MuLV induced disease; (b) a Friend MCF (Fr-MCF) virus isolated from the spleen of an F MuLV-infected mouse from a susceptible strain induced the same erythroproliferative disease when injected as an appropriate pseudotype into mice from susceptible but not resistant strains of mice; and (c) resistant but not susceptible strains of mice endogenously express MCF/xenotropic virus-related envelope glycoproteins that may be responsible for resistance by blocking receptors for MCF viruses. These results not only indicate that Fr-MCF virus is a crucial intermediate in the induction of disease by F-MuLV, but also suggest that a novel gene, either an MCF/xenotropic virus-related envelope gene or a gene controlling its expression, is responsible for resistance to erythroleukemia induced by F-MuLV. PMID- 6268736 TI - Epstein-Barr virus (EBV)-lymphoid cell interactions. I. Quantification of EBV particles required for the membrane immunofluorescence assay and the comparative expression of EBV receptors on different human B, T and null cell lines. AB - We report data on the number of Epstein-Barr virus (EBV) particles required to detect virus binding to target cells (Raji or BJA-B) by means of membrane immunofluorescence (MIF). After determining the optimum conditions for the MIF assay the following aspects of EBV-lymphoid cell interactions were examined: (i) binding of two different strains of EBV to various types of human lymphoid cell lines, (ii) expression of receptors for both EBV and complement on these lines and (iii) induction of EBV-induced nuclear antigen (EBNA) in the different target cells used. The results showed that a minimum of about 2.7 x 10(3) enveloped virus particles/cell were required for an optimum visualization of EBV binding to the target cells tested, and that a lymphoid cell may bear receptors for one prototype strain of EBV but not for the other. A number of cell lines, particularly those of T and null type which express EBV receptors, did not synthesize EBNA, thus indicating that these lines were resistant to EBV infection. Several of these lines, although expressing cell surface EBV receptors, lacked complement receptors. PMID- 6268737 TI - Induction of hepatitis B surface antigen in human hepatoma-derived cell lines. AB - Cultures of two human hepatoma cell lines were examined for expression of hepatitis B virus surface antigen (HBsAg). The PLC/PRF/5 cells secreted HBsAg continuously into the culture medium, whereas Mahlavu cells did not secrete the antigen. However, cytoplasmic antigen was detected in a low percentage (less than 5%) of the Mahlavu cells. The expression of HBsAg also was assayed in cultures treated wtih dexamethasone (DXM), 5-iodo-2'-deoxyuridine (IdUrd), or both. The results demonstrated that: (i) DXM stimulated secretion of HBsAg by PLC/PRF/5 cells but not by Mahlavu cells; (ii) the percentage of Mahlavu cells expressing cytoplasmic HBsAg was not increased in any cultures if the medium was replaced at 24 t0 48 h intervals but was increased approx. fivefold within 4 days in cultures treated with DXM or IdUrd/DXM if the medium was not changed. However, no increase was noted in the intensity of the immunoperoxidase stain of PLC/PRF/5 cells that expressed cytoplasmic antigen in any DXM cultures; (iii) HBsAg expression was stimulated to a lesser extent in IdUrd/DXM cultures than in DXM cultures and was not enhanced in IdUrd cultures. Thus, DXM enhanced secretion of HBsAg by PLC/PRF/5 cells within 24 h and, after a delay, enhanced expression of cytoplasmic antigen by Mahlavu cells. However, antigen secretion by Mahlavu cells evidently was blocked. PMID- 6268738 TI - Latency of herpesvirus of turkey and Marek's disease virus genomes in a chicken T lymphoblastoid cell line. AB - The properties of latent herpesvirus of turkey (HVT) and Marek's disease virus (MDV) genomes have been studied in virus-non-producer MDCC-BO1(T) cells, a T lymphoblastoid cell line derived from spleen cells of an HVT-vaccinated chicken. The numbers of the two virus genomes in BO1(T) cells remained stable at 1.6 to 1.8 HVT genome equivalents/cell and 3.4 to 3.8 MDV genome equivalents/cell throughout a number of passages and were not decreased by the presence of phosphonoacetic acid in the culture. When the culture temperature of the MDV producer MDCC-MSB1 cell line was shifted from 41 to 37 degrees C, the cells cultured at 37 degrees C contained about five times as many virus genomes as those cultured at 41 degrees C. In contrast, the numbers of the two virus genomes in BO1(T) cells were not increased by culture at 37 degrees C. RNA extracted from BO1(T) whole cells and from the polyribosomal fraction hybridized to both MDV and HVT DNAs, indicating the expression of both latent virus genomes. Digestion of cell nuclei with micrococcal nuclease revealed that both latent HVT and MDV genomes possess a nucleosomal structure. Closed circular MDV DNA was demonstrated in BO1(T) by isopycnic centrifugation of DNA in ethidium-bromide-CsCl gradients. PMID- 6268739 TI - Evidence for early membrane antigens in cytomegalovirus-infected cells. AB - Human cytomegalovirus (HCMV) induces membrane antigens (MA) which are detectable by immunofluorescent techniques as early as 24 h after infection. These antigens appear on the surface of infected cells in non-permissive human epithelioid and animal cells in addition to permissive human cells. The synthesis of the MA occurs in the presence of a DNA synthesis inhibitor, whereas RNA and protein synthesis inhibitors prevent its formation completely. These results demonstrate that the MA is a newly synthesized protein coded by an early function of the viral genome. PMID- 6268740 TI - Neoplastic transformation of mouse fibroblasts by murine sarcoma virus: a multi step process. AB - Infection of cultures of three different normal rodent cell lines with murine sarcoma virus (MSV) resulted in very rapid loss of contact inhibition of growth and morphological transformation. In the case of two of these lines, anchorage dependence of growth was also rapidly lost but with the 3rd, C3H10T1/2 C1.8, an established line of mouse embryo fibroblasts, there was a delay of many cell generations before the cells became anchorage independent. This was despite 100% successful infection, as assessed by focus assays of the infected cells. The acquisition of anchorage independence was correlated with a substantial increase in tumorigenicity. A number of MSV-infected clones, isolated at random from C3H10T1/2 C1.8 cultures immediately after infection with MSV, also showed a progressive increase in anchorage independence and tumorigenicity, indicating that the progressive transformation of the uncloned cells could not be entirely due to selection of rare anchorage-independent, tumorigenic clones. It was concluded that neoplastic transformation of C3H10T1/2 C1.8 cells by MSV is a multi-step process. PMID- 6268741 TI - Ribonucleoprotein of avian infectious bronchitis virus. AB - The ribonucleoprotein (RNP) of avian infectious bronchitis virus (IBV) was examined by electron microscopy after shadowing with carbon/platinum. Linear RNP strands up to 6.7 microns in length, from three IVB strains, were sensitive to both pancreatic RNase and to proteases. These strands were obtained from spontaneously disrupted complete particles but not from disrupted incomplete particles that lacked RNP. They were also released from Nonidet P40-disrupted particles and could be isolated on sucrose density gradients at a density of 1.27 g/ml. In some cases, helical RNP complexes associated with virus particles were observed that were similar to RNPs of human coronavirus strain 229E and mouse hepatitis virus strain 3. PMID- 6268742 TI - Antibody response to spike protein vaccines prepared from Semliki Forest virus. AB - Subunit vaccines, containing the spike glycoproteins of Semliki Forest virus (SFV) in three different forms, have been prepared: detergent-solubilized monomers, detergent- and lipid-free octamers, and virosomes in which the spike proteins are reconstituted into phospholipid vesicles. Previous studies have shown that the octamers and the virosomes are very efficient in protecting mice against the encephalitis caused by virulent SFV (Morein, et al., 1978). In this study we have characterized the specific antibody responses in mice vaccinated with the three SFV vaccines and correlated them with the protection against SFV encephalitis. The multimeric forms induced high humoral antibody titres; two doses of only 1 microgram protein gave rise to specific antibody titres of 0.6 mg/ml. The monomeric form was much less immunogenic. PMID- 6268743 TI - Structural polypeptides of coronavirus IBV. AB - Avian infectious bronchitis virus (IBV) was grown and radiolabelled with 35S methionine, 3H-leucine and 3H-glucosamine in de-embryonated chicken eggs. Approximately 12 different polypeptides were clearly detected by SDS polyacrylamide gel electrophoresis of virus preparations. Growth of IBV in chorioallantoic membrane cells labelled with 35S-methionine indicated that most of these polypeptides, and additional ones, some of which were glycosylated, were host components. Five polypeptides appeared to be virus-coded, with apparent mol. wt. of 94 x 10(3), 84 x 10(3), 54 x 10(3), 30 x 10(3) and 28 x 10(3). Four of these, p94, p84, p30 and p28, were glycosylated. The virion spikes appeared to be composed of p94 and p84, while p30 and p28 were partially embedded in the virion membrane. By analogy with other reports, p54 is the nucleocapsid polypeptide. PMID- 6268744 TI - Action of detergents and pre- and postsynaptic localization of 3H-naloxone binding in synaptosomal membranes. A structural approach. AB - 3H-naloxone specific binding was carried out on synaptosomal membranes isolated from basal ganglia of the cat brain. A high- and a low-affinity site with Kd1 = 3.7 nM and Kd2 = 35 nM having B max 1 = 79 pmole/g protein and B max 2 = 224 pmole/g protein were found. The Hill number for the high- and low-affinity sites were, respectively, 1.01 and 0.86. Digitonin and Triton X-100 had an inhibitory effect on the binding at concentrations between 10(-5) and 10(-1)% (w/v). Deoxycholate and Nonidet P-40 also inhibited the binding of 3H-naloxone, but at 10(-4)% produced a 50% enhancement. After the binding to membranes, the 3H naloxone receptor complex is stable to the action of Triton X-100 and dissociates slowly. In membranes bound with 10 nM 3H-naloxone and then submitted to 0.1-0.2% Triton X-100, in which only the presynaptic membrane disintegrates, the specific radioactivity is decreased. With a more drastic treatment that disintegrates the postsynaptic membrane, the 3H-naloxone binding to synaptosomal membranes is almost completely abolished. These results suggest that opiate receptors may be localized both pre- and postsynaptically in central synapses. PMID- 6268745 TI - A study of the electron transfer properties of the heme undecapeptide from cytochrome c by 1H nmr spectroscopy. AB - Nuclear magnetic resonance (nmr) spectroscopy has been used to investigate the heme undecapeptide from cytochrome c. Assignments of resonances to specific residues have been made based on spin decoupling, redox titration, and the pH and temperature dependence of resonance lines. An outline structure is presented based on the assignments, secondary shift data, and the x-ray crystal structure of cytochrome c. An equation is derived to relate the width of an nmr line during a redox titration to the percentage of each oxidation state. Using this equation the self-exchange rate constant for electron transfer for the heme peptide is 1.3 x 10(7) M-1 sec-1 at 330 degrees K. Discussion of the self-exchange rate constants of cytochrome c, cytochrome c3, and cytochrome c551 is related to this constant for the heme undecapeptide. PMID- 6268746 TI - Kinetic data for redox reactions of cytochrome c with Fe(CN)5X complexes and the question of association prior to electron transfer. AB - Use of rigorous equilibration kinetics to evaluate rate constants for the Fe(CN)6 4- reduction of horse-heart cytochrome c in the oxidized form, cyt c (III), has shown that limiting kinetics do not apply with concentrations of Fe(CN)6 4- (the reactant in excess) in the range 2-10 x 10(-4) M, I = 0.10 M (NaCl). The reaction conforms to a first-order rate law in each reactant, and at 25 degrees C, pH 7.2 (Tris), it is concluded that K for association prior to electron transfer is less than 200 M-1. From previous studies at 25 degrees C, ph 7.0 (10(-1) M phosphate), I = 0.242 M (NaCl), a value K = 2.4 x 10(3) M-1 has been reported. Had such a value applied, some or all of the redox inactive complexes Mo(CN)8 4-, Co(CN)6 3 , Cr(CN)6 3-, Zr(C2O4)4 4- present in amounts 5-20 x 10(-4) M would have been expected to associate at the same site and partially block the redox process. No effect on rats was observed. With the reductants Fe(CN)5(4-NH2-py)3- and Fe(CN)5(imid)3-, reactions proceeded to greater than 90% completion and rate laws were again first order in each reactant. Rate constants (M-1 sec-1) at 25 degrees C, pH 7.2 (Tris), I = 0.10 M (NaCl), are Fe(CN)6 4- (3.5 x 10(4)), Fe(CN)5(4 NH2py)3- (6.7 x 10(5), and Fe(CN)5(imid)3- (4.2 x 10(5). Related reactions in which cyt c(II) is oxidized are also first order in each reactant, Fe(CN)6 3- (9.1 x 10(6)), Fe(CN)5(NCS)3- (1.3 x 10(6)), Fe(CN)5(4-NH2py)2- (3.8 x 10(6) at pH 9.4), and Fe(CN)5(NH3)2- (2.75 x 10(6) at ph 8). Redox inactive Co(CN)6 3- (1.0 x 10(-3) M) has no effect on the reaction of Fe(CN)6 3- which suggests that a recent interpretation for the Fe(CN)6 3- oxidation of cyt c(II), I = 0.07 M, may also require reappraisal. PMID- 6268747 TI - Cyclic AMP in female mouse brain is altered by the adrenocorticotropic hormone(4 9) analogue organon 2766. AB - Cyclic AMP content was determined in 12 brain regions of young adult female mice at 30 min and at 24 h following an intraperitoneal injection of the tri substituted adrenocorticotropic hormone(4-9) [ACTH(4-9)] analogue Organon 2766 [ORG 2766]. Animals were killed by focused 3.5 kW microwave radiation applied for 350 ms. Unlike previously reported responses in male mice, at 30 min post injection there were no detectable differences in cyclic AMP content between the placebo and ORG 2766-treated animals. By contrast, 24 h after injection, the content of cyclic AMP was changed significantly in 8 of the 12 brain regions examined: medulla-pons, septal area, thalamus, hypothalamus, hippocampus, olfactory bulb, and parietal and occipital cortices. In most of the regions examined, differences consisted of 50% or greater reductions of tissue cyclic AMP content. The changes were unrelated to the estrus cycle of these animals. PMID- 6268748 TI - Properties of detergent-dispersed adenylate cyclase from cerebral cortex. Presence of an inhibitor protein. AB - Adenylate cyclase was solubilized from washed particulate fraction of rabbit cerebral cortex with the nonionic detergent Lubrol 12A9 and subjected to either gel filtration on Ultrogel AcA 34 or chromatography on DEAE Bio-Gel A. By both procedures the enzyme was resolved into two components, one insensitive to guanyl 5'-yl imidodiphosphate [Gpp(NH)p] and NaF but stimulated by Ca2+ and calmodulin, and another that was sensitive to Gpp(NH)p and NaF but relatively insensitive to Ca2+ and calmodulin. The data support the possibility that two independent forms of adenylate cyclase exist in cerebral cortex, one regulated by guanine nucleotide regulatory protein and another by Ca2+-calmodulin. Fractions containing the guanylnucleotide-sensitive activity were found to contain a factor that inhibited basal and Ca2+-stimulated adenylate cyclase in the Ca2+-sensitive fraction. The inhibitor was inactivated by heating at 60 degrees C and by incubation with trypsin. Inhibition was not time-dependent, and it was not due to destruction of cAMP by phosphodiesterase or of ATP by ATPase. Inhibitory action was not reversed by calmodulin and therefore it does not appear to be a calmodulin binding protein. Sucrose density gradient sedimentation indicated a sedimentation coefficient of 4S for the inhibitor; by this technique it co sedimented with the adenylate cyclase sensitive to Gpp(NH)p and NaF. PMID- 6268749 TI - Stimulus-secretion coupling in isolated adrenal chromaffin cells: calcium channel activation and possible role of cytoskeletal elements. AB - The catecholamine secretory function of a preparation of isolated bovine adrenal chromaffin cells has been further characterized under conditions designed to elucidate the mechanism of calcium channel activation and the possible role of cytoskeletal elements in stimulus-secretion coupling. Three related sets of data were obtained: (1) Differences in kinetics, Ca dependence, strength, and additivity of the secretory response to acetylcholine (ACh) versus excess K; (2) the effects on secretion of the Ca channel-blocking agents, Ni, Mg, and verapamil; and (3) the Ca dependence of vinblastine action on ACh- and K-evoked secretion. The results suggest that a major portion of the Ca influx required for catecholamine release enters the cell via voltage-dependent Ca channels with some additional Ca influx via the ACh receptor channel. Comparison of the present secretion data with corresponding known electrophysiological properties of isolated chromaffin cells provides added evidence for a role of chromaffin cell action potentials in regulation of Ca influx and the secretory response. Elevated Ca concentrations enhanced K-evoked secretion to levels comparable to that of Ach but did not induce a vinblastine block of K-evoked release. This provides further evidence against a role of microtubules in the common exocytosis event per se. However, a role of cytoskeletal elements in directing the movement of secretory granules, or an action of vinblastine at cholinergic receptors, remain distinct possibilities. PMID- 6268750 TI - The development of pre- and postsynaptic components of the noradrenergic system in the rat cerebellum. AB - Evidence based on the ability to accumulate [3H]noradrenaline by a mechanism sensitive to desmethylimipramine suggests that there is a period of hyperinnervation of the cerebellum by noradrenergic fibres around the beginning of the second postnatal week. Different developmental profiles for specific noradrenaline uptake and noradrenaline content indicate that invasion of the tissue by noradrenergic fibres precedes their full acquisition of transmitter. Developmental increases in the density of beta-receptors and adenyl cyclase responsiveness to isoproterenol lags behind those of the presynaptic components and does not begin until the hyperinnervation is declining around day 12. PMID- 6268751 TI - Long-term treatment of rats with morphine reduces the activity of messenger ribonucleic acid coding for the beta-endorphin/ACTH precursor in the intermediate pituitary. AB - Chronic administration of morphine to rats for a period of 4 weeks resulted in a 50-60% decrease in the tissue concentrations of beta-endorphin and in the in vitro release from the neurointermediate pituitary. Incorporation of [3H]phenylalanine into isolated intermediate/posterior pituitaries in vitro revealed a reduction in the amount of label incorporated into the beta endorphin/ACTH precursor to a similar extent (about 45%), but essentially no effect on the conversion of the precursor into beta-lipotropin and beta endorphin. Extraction of mRNA from intermediate/posterior pituitaries followed by cell-free translation in a reticulocyte system showed no significant decrease in the total level of translatable mRNA. In contrast, the content of translatable mRNA coding for the beta-endorphin/ACTH precursor was significantly reduced by 50 60%. Thus, long-term treatment with morphine appears to depress beta-endorphin formation in the rat intermediate pituitary at the pretranslational level by markedly decreasing the activity of mRNA coding for the beta-endorphin/ACTH precursor without any alteration in the processing of this precursor. PMID- 6268752 TI - The activity of 2',3'-cyclic nucleotide 3'-phosphodiesterase in rat tissues. AB - The activity of the myelin-associated enzyme 2',3'-cyclic nucleotide 3' phosphodiesterase (CNP) was measured in 14 rat tissues and in subcellular fractions of rat liver by a sensitive fluorometric method, using cyclic NADP as substrate. CNP activity in brain (339 mumol/h/mg protein) was fourfold that of the sciatic nerve. The activities in tissues outside the nervous system ranged from a low of 0.42 mumol/h/mg protein in the unwashed red blood cell to a high of 9.96 in the spleen. The activity was highest in tissues containing cells with membranes capable of undergoing transformation and elaboration (spleen and thymus) and low in those in which the cell membranes are morphologically stable (muscle and red cell). The enzyme was found in all major liver subfractions, with the highest activities in the microsomal and nuclear fractions. Despite the large difference in the maximal velocities of CNP in brain and liver, the affinity of the liver enzyme for the substrate (km) was similar to that of brain enzyme. Brain CNP was stable over a 48-h postmortem period. PMID- 6268754 TI - Benzodiazepine antagonist Ro 15-1788: binding characteristics and interaction with drug-induced changes in dopamine turnover and cerebellar cGMP levels. AB - The recently discovered benzodiazepine antagonist Ro 15-1788 was characterized in binding studies, and its potency and selectivity were determined in vivo by interaction with drug-induced changes in dopamine turnover and cerebellar cGMP level. Ro 15-1788 reduced [3H]flunitrazepam binding in the brain in vivo with a potency similar to that of diazepam and effectively inhibited [3H]diazepam binding in vitro (IC50 = 2.3 +/- 0.6 nmol/liter). [3H]Ro 15-1788 bound to tissue fractions of rat cerebral cortex with an apparent dissociation (KD) of 1.0 +/- 0.1 nmol/liter. The in vitro potency of various benzodiazepines in displacing [3H]Ro 15-1788 from its binding site was of the same rank order as found previously in [3H]diazepam binding. Autoradiograms of [3H]Ro 15-1788 binding in sections of rat cerebellum showed the same distribution of radioactivity as with [3H]flunitrazepam. The attenuating effect of diazepam on the chlorpromazine- or stress-induced elevation of homovanillic acid in rat brain was antagonized by Ro 15-1788. Among a series of compounds which either decreased or increased the rat cerebellar cGMP level, only the effect of benzodiazepine receptor ligands (diazepam, zopiclone, CL 218 872) was antagonized by Ro 15-1788. Thus, Ro 15-1788 is a selective benzodiazepine antagonist acting at the level of the benzodiazepine receptor in the central nervous system. Peripheral benzodiazepine binding sites in kidney and schistosomes were not affected by Ro 15-1788. PMID- 6268753 TI - Investigations on myelination in vitro: regulation of 2,3'-cyclic nucleotide 3' phosphohydrolase by thyroid hormone in cultures of dissociated brain cells from embryonic mice. AB - The direct influence of L-3,3',5-triiodothyronine (T3) on the development of 2',3'-cyclic nucleotide 3'-phosphohydrolase (EC 3.1.4.37, CNPase) is demonstrated by using an in vitro culture system of dissociated embryonic mouse brain cells. Serum from a thyroidectomized calf, which contained low levels of T3 (31 ng/100 ml), and thyroxine, T4 (less than 1 micrograms/ml), was used in the culture medium in place of normal calf serum (T3, 103 ng/100 ml; T4, 5.7 micrograms/ml) to render the culture responsive to exogenously added T3. The lower levels of enzyme activity observed in the presence of such a deficient medium could be restored to normal values by T3 supplementation. Half-maximal effect was obtained with 2.5 X 10(-9) M-T3. Three days of hormone treatment resulted in the maximal stimulation of CNPase. T4 was less effective in inducing CNPase activity and the inactive analog of the hormone, reverse T3 (3,3',5'-T3) was ineffective. The morphological appearance of the cells was characterized by deformed (smaller size and less in number) reaggregates in the cultures, lacking hormone. PMID- 6268755 TI - Involvement of brain monoamines in the delta-9-tetrahydrocannabinol-induced reduction of hippocampal choline uptake. AB - The role of monoamines in the transsynaptic reduction of neuronal activity produced by delta 9-tetrahydrocannabinol (delta 9-THC) in the septal-hippocampal cholinergic pathway has been investigated. Serotonergic afferents were chemically lesioned by unilateral infusion of 5,7-dihydroxytryptamine. Noradrenergic and dopaminergic inputs were selectively deleted by unilateral infusion of 6 hydroxydopamine into appropriate anatomic sites. Although removal of serotonergic and noradrenergic input did not alter hippocampal choline uptake relative to the contralateral control side, dopaminergic input reduction produced a significant elevation. After administration of delta 9-THC (20 mg/kg), reduction of choline uptake into lesioned hippocampi was not significantly different from that for the controls. These results indicate that monoaminergic afferents do not play a major role in the effect of delta 9-THC on cholinergic activity in the rat hippocampus. PMID- 6268756 TI - Hereditary motor and sensory neuropathy of neuronal type with onset in early childhood. AB - Eleven cases of a severe neuropathy with onset in early childhood are described. The condition commences with distal weakness and wasting of the lower limbs and subsequently involves the hands, causing severe paralysis of the hands and feet towards the end of the second decade. Sensory changes are common but are usually only mild. The peripheral nerves are not enlarged. Claw hand, scoliosis and other orthopaedic deformities are seen in the later stages. CSF protein is not elevated and there is only mild slowing of motor conduction velocities. The pathological changes in sural nerve biopsies are those of axonal degeneration affecting myelinated and unmyelinated fibres. Family studies suggested autosomal recessive inheritance in two kindreds and dominant inheritance in another. Five cases were sporadic. The condition is clinically more severe and of earlier onset than hereditary motor and sensory neuropathy (HMSN) type II and differs electrophysiologically and pathologically from Dejerine-Sottas disease. PMID- 6268757 TI - Central nervous system vasculitis in cytomegalovirus infection. AB - A 51-year-old man received cyclophosphamide, vincristine, procarbazine and prednisone in the treatment of a small-cell undifferentiated lymphoma. Two years later, he developed a rapidly progressive neurological syndrome characterized by a decline in alertness, deafness, blindness and paraplegia. Examination of his eyes revealed severe hemorrhagic chorioretinitis. Leg weakness was thought to be due to transverse myelopathy at a thoracic level. He had a grand mal convulsion and died from terminal bronchopneumonia. Autopsy examination of the eyes revealed sweeping destruction of the retina due to inclusion body chorioretinitis. The brain and spinal cord showed multiple small infarcts accounting for the deafness and paraplegia. The lesions were due to occlusive arteritis in gray and white matter. Veins were also involved. Tissue surrounding the foci of necrosis contained cells with intranuclear an intracytoplasmic inclusion bodies. Some of the Cowdry type A inclusion bodies were large, measuring 30 micrometer in diameter and were located in enlarged cells. Electron microscopy of retina and brain tissue disclosed virus particles compatible with cytomegalovirus. The subject of cerebral and ocular angiitis due to herpes virus infections is reviewed. PMID- 6268758 TI - Calcium flux of erythrocytes in Duchenne muscular dystrophy. AB - The calcium flux of erythrocytes from patients with Duchenne muscular dystrophy (DMD) was measured. Passive influx was determined using erythrocytes incubated with lanthanum chloride as a specific inhibitor to calcium transport. There was no significant difference in calcium influx into cytosol and into membrane fractions between DMD and control age-matched boys. Influx of calcium was also determined using ATP-depleted erythrocytes incubated without the inhibitor. Again there was no significant difference between DMD and control values. Efflux of calcium was measured using erythrocytes loaded with calcium ionophore A23187. Calcium efflux speed was related to intracellular calcium concentration and the efflux reached a plateau at about 1 mM. There was no significant difference in calcium efflux rate as a function of intracellular calcium concentration between DMD and control. PMID- 6268759 TI - Quantitative measurement of [3H]ouabain binding to human skeletal muscle cryostat sections. AB - The etiopathogenesis of myotonic muscular dystrophy is thought to involve a basic defect in muscle membrane. Biochemical investigations of human muscle membrane have been hampered by difficulty in obtaining large quantities of muscle at biopsy for the preparation of sarcolemma. We have determined [3H]ouabain binding to normal and myotonic dystrophy human skeletal muscle by using cryostat sections. The binding increased with increase in number of tissue sections (protein) and in concentrations of [3H]ouabain, ATP and Na+. The binding of [3H]ouabain in myotonic dystrophy patients was 2-3 fold higher than in normal and disease controls. Kinetic analysis revealed that the increased binding of ouabain to myotonic tissue sections was independent of low-affinity sites directed by ATP and Na+. These findings provide further evidence for the involvement of membrane abnormalities in myotonic muscular dystrophy. PMID- 6268760 TI - Neuropeptides in Alzheimer's disease, depression and schizophrenia. A post mortem analysis of vasoactive intestinal peptide and cholecystokinin in cerebral cortex. AB - Vasoactive intestinal peptide (VIP) and cholecystokinin (CCK) have been measured, by radioimmunoassay, in cerebral cortex obtained at autopsy from patients without neurological or psychiatric disease and from patients with Alzheimer's disease, depression and schizophrenia. Sephadex gel filtration indicated that over 90% of the CCK immunoreactivity was associated with the octapeptide in extracted material from the different clinical groups investigated. There were no significant differences from the normal in the overall concentrations of either VIP or CCK in any of the psychiatric groups examined, although differences in Alzheimer's disease were apparent when cases were grouped according to postmortem delay. PMID- 6268761 TI - Growth characteristics of human glioma-derived and fetal neural cells in culture. AB - Growth characteristics of human fetal neural cells (CH) and human glioblastoma multiforme-derived cells (12-18) in culture were compared. Cells were grown to confluent densities of 38,000 to 42,500 cells/cm2 for CH and 85,800 to 87,100 for 12-18. Population doubling times were 40.0 +/- 5.1 hr and 66.5 +/- 9.8 hr for CH and 12-18 cells, respectively. The mean DNA content per cell of the glioma derived cells was twice that of the fetal brain cells at sparse, log, and confluent cell densities. High concentrations (40%) of serum in growth medium increased DNA contents in confluent CH, but not 12-18, cells. The amount of protein per cell also was consistently higher in glioma cells than CH cells, but, as cell densities increased, protein contents decreased for both: 1200 to 700 pg/cell in glioma cells, and 840 to 560 pg/cell in CH cells. In each cell line, initial rates of [3H]ThdR incorporation into TCA precipitable material decreased as cell density increased, but confluent glioma-derived cells incorporated 10 times more [3H]ThdR than confluent fetal cells. Almost all CH cells had a normal diploid chromosome number of 46. A histogram showing the relative frequencies of chromosome numbers of glioma-derived cells had peaks of 52, 79, and 105 chromosomes per metaphase, indicating a haploid number of 26 for most cells. Lengths of cell cycle phases, determined using autoradiographic techniques, indicate that glioma-derived cells had a longer generation time and S period than fetal neural cells. These data demonstrate several biological differences between glioblastoma-derived cells and non-neoplastic fetal neural cells, indicating that this system is of potential value for comparative studies on growth control and contact inhibition. PMID- 6268762 TI - Re: decreased salivary gland accumulation of pertechnetate in neonatal hypothyroidism. PMID- 6268763 TI - Tc-99m sulfur colloid scintigraphy of multiple liver-cell adenomas. PMID- 6268764 TI - Method of addition of cellulose to experimental diets and its effect on rat growth and protein utilization. AB - The growth response of rats to experimental diets limiting in protein was used to evaluate two modes of addition of fiber. The first mode (trial A) used the more conventional approach of substituting cellulose for starch. The second mode (trial B) proceeded by total diet dilution, by which cellulose was added to a cellulose-free stock diet. Rats fed both types of diets compensated for the energy dilution and their digestible energy intake did not change markedly. However, both protein intake and growth increased with rising dietary cellulose levels in trial A and the protein efficiency ratio (PER) decreased. These did not change in trial B, except at the highest cellulose level, where growth and PER tended to decrease. Not only did the total diet digestibility and gross energy digestibility diminish upon the addition of cellulose to the diet, but the apparent protein digestibility also decreased in response to increasing dietary cellulose. We concluded that, in the design of experiments using high-fiber diets, careful consideration should be given to the effect which the method of dietary fiber addition has on the effective concentration of nutrients in the non fiber portion of the diet and to the effect which variations in the parameter might have on nutrient utilization or biological responses to them. Our results indicate that, under conditions where protein is in limiting amounts in the low fiber diets, total diet dilution is the more appropriate mode of dietary fiber addition. This conclusion may apply to other nutrients as well, but that remains to be proved. PMID- 6268765 TI - Tissue distribution, uptake, and requirement for alpha-tocopherol of rainbow trout (Salmo gairdneri) fed diets with a minimal content of unsaturated fatty acids. AB - The metabolism of and requirements for alpha-tocopherol in rainbow trout fed diets containing 1% linolenic acid as sole source of unsaturated fat and graded levels of tocopherol (0.06-10 mg/100 g) were examined. Fish grew 5-fold over a 16 week period. In liver, tocopherol was concentrated in mitochondria with little in cytosol. Orally administered [3H]-tocopherol was rapidly taken up by plasma and liver but uptake into erythrocytes and white muscle was much slower; in most tissues radioactivity reached a plateau after about 3 days but in red muscle radioactivity increased over a 10-day period. Activities of enzymes that prevent free radical initiated tissue damage did not change in tocopherol deficiency. Tocopherol-deficient trout had no gross or subcellular pathologies even though liver and muscle were severely depleted of the vitamin. Ascorbic acid-stimulated lipid peroxidation in liver organelles indicated a tocopherol requirement of 2-3 mg/100 g diet; the molar ratios of polyunsaturated fatty acids to tocopherol in livers of trout fed diets lacking or supplemented with tocopherol (100 mg/100 g) were 980 and 170, respectively. PMID- 6268766 TI - Fibrous zeolites and endemic mesothelioma in Cappadocia, Turkey. PMID- 6268768 TI - Nasopharyngeal viral isolates in children with Haemophilus influenzae type B meningitis. PMID- 6268767 TI - Diverse profiles of immunoreactivity in toluene diisocyanate (TDI) asthma. AB - Possible immunoreactivity to chemically well-characterized mono- and diisocyanate protein conjugates was reevaluated in 15 workers with TDI asthma and 17 normal (nonexposed) volunteers. Lymphocytes of nine sensitive workers were incubated with TDI human serum albumin (HSA) conjugates. Leucocyte inhibitory factor (LIF) was produced. Leucocyte inhibitory factor was also induced by hexamethylene diisocyanate (HDI) protein conjugates in four of these workers who had no prior history of exposure to HDI. Disappearance of TDI- and HDI-induced LIF was noted in several sensitive workers who were removed from further TDI exposure. Three LIF-positive workers also demonstrated positive intracutaneous reactivity to TDI HSA. One workers had a markedly positive RAST (25.5% binding) to a monofunctional (p-tolyl isocyanate) protein reagent. These studies suggest that isocyanates have the potential for eliciting heterogeneous immune responses in certain subpopulations of exposed workers. Continued contact with isocyanates may be necessary for maintenance of specific immunity. Possible cross reactivity between TDI and HDI may be determined by new antigenic sites created by isocyanate protein interactions. PMID- 6268769 TI - Clear cell sarcoma of the kidney in children: a distinct entity. AB - Four cases of clear cell sarcoma of the kidney in children are reported. The specificity of the tumor is examined. The pathologic features, the clinical presentation, and the occurrence of bone metastasis are reasons to distinguish clear cell sarcoma from the Wilms' tumor group. The poor prognosis may be improved in the future by radical resection associated with polyvalent chemotherapy. PMID- 6268770 TI - Identification and determination of 11-oxo-delta8-tetrahydrocannabinol as an intermediate metabolite of delta8-tetrahydrocannabinol in the mouse brain and liver. AB - 11-Oxo-delta 8-tetrahydrocannabinol (11-oxo-delta THC) was found in the mouse brain and liver extracts as a new in vivo metabolite of delta8-THC. The metabolite was detected by thin-layer chromatography using two aldehyde reagents together with a phenol reagent and identified as a heptafluorobutyrate by ECD-gas chromatography. This identification was further supported by gas chromatography mass spectrometry. Content of the metabolite in the mouse liver was 0.09 or 0.19 microgram/g at 15 min after the i.v. injection of delta8-THC or 11-hydroxy-delta8 THC (11-OH-delta8-THC) at a dose of 10 mg/kg. On the contrary, 11-oxo-delta 8-THC was not precisely quantified (less than 0.01 microgram/g) in the brain after injection of delta 8-THC, although its content after the injection of 11-OH-delta 8 THC was 0.03 microgram/g. PMID- 6268771 TI - Quisqualate action on the crayfish neuromuscular junction. AB - Actions of quisqualic acid on the crayfish neuromuscular junction were examined and compared with those of glutamate. The glutamate and quisqualate currents were induced in the voltage-clamped muscle. When their peak amplitudes were plotted against the current intensity of iontophoretically applied drugs, the hyperbola resulted. The amplitude of the maximum response to quisqualate was similar to that to glutamate. When the amount of quisqualate which was simultaneously applied with glutamate was changed, the amplitudes of the maximum response of glutamate plus quisqualate did not vary much at the top of the dose-response curves. Bath application of quisqualate in concentrations above 10(-6) M produced a large depolarization of the muscle fiber, but this response was maintained after it reached a maximum, unlike glutamate. On the other hand, the amplitude of excitatory junctional potential (EJPs) was gradually decreased. A quantum analysis of the extracellular EJP demonstrated that this decrease in EJP amplitude produced by quisqualic acid was due to the postsynaptic event. This decrease in EJP amplitude could not be prevent by exposure of the muscle fiber to concanavalin A, which completely blocked development of desensitization of the glutamate receptor. Based on these results, it is doubtful that the decrease in EJP amplitude produced by quisqualic acid is due to desensitization of the neuroreceptor. PMID- 6268772 TI - Localization of sodium pump sites in cat pancreas. AB - 1. Cat pancreases were exposed to [3H]ouabain either by perfusion, or by incubation of slices, with Krebs--Henseleit bicarbonate solution containing [3H]ouabain, and [3H]ouabain binding sites were localized by light microscopical autoradiography. 2. Acinar cells were found to possess only a few [3H]ouabain binding sites located on the basolateral plasma membranes. 3. The epithelial cells lining the intercalated and interlobular ducts were heavily labelled. The [3H]ouabain binding sites were located on the basolateral membranes. 4. Since secretion of pancreatic juice can be abolished by ouabain, it is concluded that the duct cells, especially those of the numerous small (intercalated) and intermediate-sized (interlobular) ducts are responsible for pancreatic secretion of electrolytes and water. 5. The localization of the (Na+ + K+)-activated ATPase to the basolateral membranes of the cells excludes a direct role of the transport enzyme in the secretion of Na+. However, a model is proposed where the Na+ + K+) activated ATPase plays a crucial, though indirect role in pancreatic secretion of electrolytes and water. PMID- 6268773 TI - Evidence for the presence of potassium channels in the paranodal region of acutely demyelinated mammalian single nerve fibres. AB - 1. A study has been made of the ionic currents in voltage-clamped single rabbit nodes of Ranvier at 22-26 degrees C both under normal conditions, and after the nerve fibres had been acutely demyelinated by a variety of treatments designed to lossen the myelin from the axonal membrane. 2. The myelin-loosening treatments included application of various combinations of: lysolecithin (to dissolve the myelin); collagenase (to loosen the connective tissue in the nodal region); high potassium Locke solution, hypertonic and hypotonic solutions (to induce axonal volume changes). 3. At a critical stage in such treatment (usually after 15-45 min) a large outward current suddenly appeared. 4. There was no substantial change in the size of the measured inward sodium current when measured at this critical stage. 5. The outward current was blocked by internal TEA and caesium ions, had a reversal potential that became more positive when the external potassium concentration was increased, was kinetically similar to the known potassium current in frog fibres, and was therefore assumed to be a potassium current. 6. The phase of large outward current, whenever it appeared, was always accompanied by the appearance of a slow transient capacitative component in the leakage current, which indicated a marked increase in the effective nodal capacity (of 10- to 60-fold). We suggest that the slow transient capacity current reflected charging of newly exposed axonal membrane, probably in the paranodal region, which was uncovered by the various acute demyelination treatments. This internodal membrane seems to contain mostly potassium channels and few, if any, sodium channels. 7. Newly dissected fibres occasionally showed large potassium currents before treatment, particularly if they were deliberately stretched during dissection; a marked slow capacity transient current was consistently present in these fibres. 8. The effects of acute paranodal demyelination on the sodium and potassium currents, and on the transient capacity currents, can be simulated by a model in which the node is coupled to a cable-like paranode which contains Hodgkin--Huxley type potassium channels and which has a much higher leakage resistance. 9. The functional significance of the presence of potassium channels in rhe internodal region (at least in the paranode) of mammalian fibres is discussed. PMID- 6268774 TI - [Vasopressin isoreceptors in the liver and kidney: relationship between hormone binding and biological response]. AB - Two type of vasopressin receptors can be distinguished on the basis of their relation to adenylate cyclase. V1 renal receptors are coupled to adenylate cyclase; V2 receptors, present, for example, in liver and blood vessels, are not coupled to adenylate cyclase. V1 and V2 receptors also differ with respect to their abilities to discriminate between several structural analogues of vasopressin. V1 and V2 receptors, present in several cellular and homologous acellular preparations (isolated hepatocytes and live membranes, renal cells in culture and renal membranes), have been characterized using tritiated vasopressin. Dissociation constants for vasopressin binding to intact cells are comparable to dissociation constants for binding to acellular preparations. In all systems studied, a marked amplification of the hormonal signal can be demonstrated. PMID- 6268775 TI - [Role of ADH-induced intramembrane particle aggregates (author's transl)]. AB - In certain epithelial tissues, water permeability is markedly increased by antidiuretic hormone. This so-called hydrosmotic effect has been shown to be mediated by 3'-5' cyclic adenosine monophosphate, which, in turn, alters the permeability o the luminal membrane of receptor cells. This review deals wity ultrastructural alterations occurring in the membrane, as observed with freeze fracture electron microscopy. Basically, these alterations consist of organized particle aggregates which appear in the apical membrane. In all experimental conditions, similar aggregates can be observed in the membrane of cytoplasmic vesicles. ADH stimulation triggers the fusion of these vesicles with the apical membrane resulting in the concomitant transfer of particle aggregates. It has been shown, in a wide range of experimental conditions, that both number and total area of the aggregates are directly proportional to the water permeability of the tissue. It is generally assumed that particle aggregates contain transmembrane channels that are selectively to water. PMID- 6268776 TI - The mode of action of vasopressin: membrane microstructure and biological transport. AB - Vasopressin affects a variety of cell systems. This review is focused on permeability changes induced by vasopressin in tight epithelia such as the collecting duct of the mammalian kidney and the skin and the bladder of anurans. These vasopressin effects are discussed with reference to current concepts and models of the microstructure of the plasma membrane. The transport of three major chemical species--Na, urea and water--is analyzed. In each instance, the hormone appears to activate selective membrane pathways situated at the rat-limiting barrier of the epithelium, i.e., the apical membrane. Available data suggest that two intra-cellular messengers -- cAMP and calcium -- plan a key role in the coupling between stimulus (receptor occupancy) and biological effect (permeability change). The enhancement of Na transport (natriferic effect) depends on the opening and/or the insertion of Na channels, the biophysical and biochemical characteristics of which have been investigated by fluctuation analysis and by means of several chemical blockers of Na transport, particularly the amiloride molecule and its congeners. Likewise, the finding of inhibitors and activators of urea transport, which do not cause any appreciable change in Na or water permeability, led to the notion of selective urea channels or pores. Finally, the enhancement of water transport (hydrosmotic effect) possibly results from the insertion in the apical membrane of water channels already present in vesicular cytoplasmic structures. The restructuring of the apical membrane underlying the transition from a low to a higher state of water permeability is very likely related to the appearance of intramembrane particle aggregates detectable with the freeze-fracture technique in epithelia exposed to vasopressin. The putative water channels (or pores) appear to be so narrow that trans-apical water movement is constrained to single-file diffusion. Recent data also suggest that, in addition to cAMP, microtubules and microfilaments, the calmodulin-Ca complex is a major element in the hydrosmotic effect of vasopressin. PMID- 6268778 TI - Values and nursing ethics: a bibliography. PMID- 6268777 TI - Scapegoating: manifestation and intervention. PMID- 6268779 TI - Phenomenon of early engagement in family therapy. PMID- 6268780 TI - Family therapy for the multiple incest family. PMID- 6268781 TI - Brain opiates and corticotrophin-related peptides. The Goulstonian Lecture 1980. PMID- 6268782 TI - Acute viral hepatitis. PMID- 6268783 TI - Is oestrogen therapy effective in the treatment of menopausal depression? AB - Fifty-five depressed menopausal patients took part in a randomized double-blind cross-over trial using ;Harmogen' (piperazine oestrone sulphate) and placebo. The Beck depression inventory, hot flush counts, and patients' subjective assessment of well-being were used to assess clinical status. Hormonal, biochemical and coagulation profiles were carried out. Hot flushes improved significantly on oestrogen compared with placebo. Depression scores and well-being showed significant and equal improvement on oestrogen and placebo. Significant improvement in flushes in patients on placebo was observed in the first half of the trial but did not occur in the second half, in patients who had previously taken oestrogen. No significant changes occurred in biochemistry. Coagulation tests showed acceleration of the prothrombin time in patients taking ;Harmogen' compared with those on placebo. Piperazine oestrone sulphate is a relatively weak but safe oestrogen preparation, effective in treatment of vasomotor symptoms but no more effective than placebo in the treatment of depression. PMID- 6268785 TI - Plasma cortisol levels in pigs susceptible and resistant to malignant hyperthermia. AB - Plasma cortisol levels were measured in Landrace pigs susceptible to malignant hyperthermia (MH), Landrace pigs resistant to MH and in Largewhite pigs, during growth halothane anaesthesia and after injections of Synachten. From 3 to 6 months of age mean cortisol levels in susceptible Landrace were 193,2 +/- 49,7 nmol/l, in resistant Landrace 220,8 +/- 24,8 nmol/l and in Largewhite 278,8 +/- 13,8 nmol/l. These values were not significantly different. After injection of 1 mg Synachten intravenously, plasma cortisol levels did not increase significantly in susceptible pigs. In resistant landrace pigs and Largewhite pigs the plasma levels after injection were significantly greater than pre-injection levels (P less than 0,05) and significantly different from susceptible Landrace levels. During halothane anaesthesia, cortisol levels rose more in resistant pigs than in susceptible pigs, but differences were no significant. These results suggest that susceptible pigs have a decreased ability to secrete cortisol during stress. PMID- 6268784 TI - The after-care of abortion patients. PMID- 6268786 TI - Opiate receptor interaction of compounds derived from or structurally related to fentanyl. AB - The opiate receptor affinity of compounds derived from or structurally related to fentanyl (1) was determined by in vitro receptor binding assays. The relatively high affinity of fentanyl (3 times morphine) was hardly influenced by the introduction of a 2-CH3, 2-OCH3, or a 2-Cl substituent into the anilino phenyl and was moderately reduced by 2-C2H5, 2-OC2H5, and 2,6-(CH3)2 substitution in this ring. Removal of the n-propionyl g in vitro receptor binding assays. The relatively high affinity of fentanyl (3 times morphine) was hardly influenced by the introduction of a 2-CH3, 2-OCH3, or a 2-Cl substituent into the anilino phenyl and was moderately reduced by 2-C2H5, 2-OC2H5, and 2,6-(CH3)2 substitution in this ring. Removal of the n-propionyl g in vitro receptor binding assays. The relatively high affinity of fentanyl (3 times morphine) was hardly influenced by the introduction of a 2-CH3, 2-OCH3, or a 2-Cl substituent into the anilino phenyl and was moderately reduced by 2-C2H5, 2-OC2H5, and 2,6-(CH3)2 substitution in this ring. Removal of the n-propionyl group of the 2-OCH3 derivative, fixation of the anilino phenyl in fentanyl to the propionyl group or the piperidine ring, and replacement of the amide N by C all caused a sharp decline of receptor affinity. Examination of molecular models seemed to indicate that optimal opiate receptor interaction of fentanyl and its derivatives requires a virtually perpendicular position of the anilino phenyl with respect to the amide function. PMID- 6268787 TI - Allylprodine analogues as receptor probes. Evidence that phenolic and nonphenolic ligands interact with different subsites on identical opioid receptors. AB - The m-hydroxy analogues of allylprodine and related structures have been synthesized and tested for narcotic agonist and antagonist activity on the electrically stimulated guinea pig ileum and by the hot-plate procedure in mice. It has been found that m-hydroxyallylprodine (alpha-2) is neither an agonist nor antagonist. Other phenolic congeners similarly have little or no activity. The fact that these results are in dramatic contrast with the structure-activity profile of morphine and closely related opiates has led to the proposal that the interaction of morphine and allylprodine (alpha-1) with the mu opioid receptor differs. This difference is postulated to arise from the recognition of the aromatic groups of morphine and alpha-1 by different aromatic-binding subsites of the receptor. These subsites are suggested to be identical with those which recognize the aromatic rings of the Tyr1 and Phe4 of the enkephalins and endorphins. A receptor model consistent with these results is proposed. PMID- 6268788 TI - Epimeric cis-decahydroquinoline-5-carboxylic acids: effects on gamma-aminobutyric acid uptake and receptor binding in vitro. AB - The syntheses for two cis-decahydroquinoline-5-carboxylic acid epimers (1 and 2) which contain the =N(C)3CO2H (gamma-aminobutyric acid; GABA) moiety are described. Both intra-and intermolecular [4 + 2] cycloaddition reactions were employed for the construction of key intermediates. 1H NMR studies provided evidence for the preferred solution conformations of the two diastereomers. Pharmacological studies revealed that these isomers have little affinity for GABA receptors in vitro relative to GABA agonists. However, expected but weak stereoselective activity was observed when these analogues were assessed for their ability to inhibit high-affinity [3H]GABA uptake into rat brain synaptosomes. These data are discussed in light of structure-activity studies of other neurotransmitter analogues, and a preliminary hypothesis based upon conformational analysis is presented to explain the results. PMID- 6268789 TI - Synthesis of analogues of acetylmethadol and methadol as potential narcotic antagonists. AB - The N-allyl and N-(cyclopropylmethyl) analogues of (-)-alpha-acetylmethadol and ( )-alpha-methadol have been synthesized and evaluated for opiate agonist and opiate antagonist activity. Both acetylmethadol analogues possessed weak analgesic activity in vivo tests for narcotic analgesia; the N-allyl analogue partially antagonized morphine-induced tail-flick analgesia. All four compounds possessed only opiate agonist-like activity as determined by in vitro studies measuring inhibition of [3H]naloxone binding to opiate receptors. PMID- 6268790 TI - ATP-dependent calcium transport by a Golgi-enriched membrane fraction from mouse mammary gland. AB - Crude particulate preparations from the mammary glands of lactating mice were shown to transport calcium against a concentration gradient in the presence of ATP and mitochondrial inhibitors. Density gradient centrifugation with both sucrose and Percoll gradients indicated the presence of ATP-dependent transport in more than one membrane fraction. A Golgi-enriched membrane fraction possessed the highest specific activity of calcium transport. Digitonin, which increases the permeability of plasma membranes to calcium, did not affect this process. The Golgi fraction contained a 100,000 Dalton protein whose phosphorylation by gamma [32P]-ATP was enhanced by a micromolar concentrations of free calcium. The phosphorylation was acid-stable and hydroxylamine-sensitive. These properties suggest that Golgi membranes in an activity secreting mammary epithelium possess a calcium transport system which resembles the calcium ATPase present in the sarcoplasmic reticulum of skeletal muscle. PMID- 6268791 TI - Evidence for activation of an active electrogenic proton pump in Ehrlich ascites tumor cells during glycolysis. AB - The addition of glucose to a suspension of Ehrlich ascites tumor cells results in rapid acidification of the extracellular medium due to lactic acid production. The nature of the H+ efflux mechanism has been studied by measuring the time course of the acidification, the rate of proton efflux, the direction and relative magnitude of the H+ concentration gradient, and the voltage across the membrane. Using the pH-sensitive dye acridine orange, we have established that after addition of 10 mM glucose an outward-directed H+ concentration gradient develops. As the rate of glycolysis slows, the continued extrusion of H+ reverses the direction of the H+ concentration gradient. Changes in absorbance of the voltage-sensitive dye diethyloxadicarbocyanine iodide (DOCC), and changes in the distribution of the lipid permeant cation tetraphenyl phosphonium, showed a dramatic and persistent hyperpolarization of the membrane voltage after glucose addition. The hyperpolarization was prevented by the protonophore tetrachlorosalicylanalide (TCS) and by valinomycin, but not by the neutral exchange ionophore nigericin. Inhibitors of lactate efflux were found to reduce the rate of acidification after glucose addition but they had no effect on the magnitude of the resulting hyperpolarization. On the basis of these and other data we suggest that an active electrogenic pump mechanism for H+ efflux may be activated by glucose and that this mechanism operates independently of the lactate carrier system. PMID- 6268793 TI - Time dependence of the effect of p-chloromercuribenzoate on erythrocyte water permeability: a pulsed nuclear magnetic resonance study. AB - Pulsed nuclear magnetic resonance spectroscopy is employed to determine the time dependence of the change in erythrocyte water permeability following exposure to p-chloromercuribenzoate (PCMB) or p-chloromercuribenzene sulfonic acid (PCMBS). pH variation was used to examine the environment of the sulfhydryl groups reactive to these drugs. PCMB reacted with at least two sulfhydryl groups which affect water permeability. This was shown by the double exponential character of the change in erythrocyte diffusional permeability with time after PCMB addition. However, only one inhibition rate process could be distinguished following PCMBS exposure, suggesting that one site bound by PCMB is not accessible to PCMBS. This site is postulated to be located in a hydrophobic region of the membrane, whereas the site reached by both drugs is located in the normal anion permeation channel. The effect of pH on the degree of inhibition due to each component and the inhibition rates is explained in terms of its effect on solubility of the reagents in the membrane and variation of the dissociated-to-undissociated ratio of PCMB. PMID- 6268792 TI - Regulation of passive potassium transport of normal and transformed 3T3 mouse cell cultures by external calcium concentration and temperature. AB - Regulation of passive potassium ion transport by the external calcium concentration and temperature was studied on cell cultures of 3T3 mouse cells and their DNA-virus transformed derivatives. Upon lowering of external calcium concentration, passive potassium efflux generally exhibits a sharp increase at about 0.1 mM. The fraction of calcium-regulated potassium efflux is largely independent of temperature in the cases of the transformed cells, but shows a sharp increase for 3T3 cells upon increasing temperature above 32 degrees C. In the same range of temperature, the 3T3 cells exhibit the phenomenon of high temperature inactivation of the residual potassium efflux at 1 mM external calcium. At comparable cellular growth densities, the transformed cell lines do not show high-temperature inactivation of "residual" potassium efflux. These results are consistent with the notion of a decisive role of the internal K+ concentration in the cell-density dependent regulation of cell proliferation. In particular, the growth-inhibiting effect of lowering the external Ca2+ concentrations is considered as largely due to a rise of passive K+ efflux and a subsequent decrease of internal K+ concentration. The experimental data on the Ca2+ dependence of passive K+ flux are quantitatively described by a theoretical model based on the constant field relations including negative surface charges on the external face of the membrane, which cooperatively bind Ca2+ ions and may concomitantly undergo a lateral redistribution. The present evidence is consistent with acidic phospholipids as representing these negative surface charges. PMID- 6268794 TI - Thallium interaction with the gastric (K, H)-ATPase. AB - The gastric (K, H)-ATPase has been shown to catalyze an electroneutral H+ for K+ exchange. Tl+ is able to substitute for K+ as an activating cation in the hydrolytic reaction with an apparent dissociation constant of 90 microM as compared to about 870 microM for K+. The ability of Tl+ to participate in transport is shown by the development of pH gradients in the presence of Tl+ following addition of ATP to gastric vesicles and by the ATP-dependent efflux of Tl+ from gastric vesicles. Inhibition of hydrolysis is observed at pH 7.4 with external Tl+ concentrations above 3.0 mM. This inhibition of hydrolysis is correlated with inhibition of pH-gradient formation. The inhibition of transport activity is partially relieved by a decrease in medium pH. This inhibitory effect is attributed to Tl+ binding at an external, low affinity cation site. In contrast to rubidium chloride, at high Tl+ concentrations, following the initial Tl+ efflux, there is reuptake of the cation. This rapid uptake is attributed to lipid-dependent Tl+ entry pathways. The vesicles exhibit a high permeability to thallium nitrate demonstrating a half-time (t1/2) for uptake of about 1.0 min in contrast to 46 min for rubidium chloride. In both gastric vesicles or liposomes, external Tl+ concentrations in excess of 1 to 4 mM are able to dissipate intravesicular proton gradients. Thus, although Tl+ is able to activate the gastric ATPase by mimicking K+, the permeability of this cation in lipid bilayers tends to uncouple H+ transport at concentrations high enough to generate detectable proton gradients. PMID- 6268795 TI - Malignant fibrous histiocytoma arising in bone. PMID- 6268796 TI - Restriction and modification enzymes detect no allosteric changes in DNA with bound lac repressor or RNA polymerase. PMID- 6268797 TI - Cyclic adenosine monophosphate modulation of contractility via slow Ca2+ channels in chick heart. PMID- 6268799 TI - Inhibition of the slow response action potential during the aftercontraction in mammalian heart muscle. PMID- 6268798 TI - Effects of quinidine, procainamide and disopyramide on automaticity and cyclic AMP content of guinea-pig atria. PMID- 6268800 TI - Condensation of activated diguanylates on a poly(C) template. AB - We have studied the metal-ion catalysis of a number of reactions of the isomers of ImpGpG on a poly(C) template. In the absence of a catalytic metal ion, oligomers at least up to (pG)20 are obtained from the ImpGpG isomers in a 1 methylimidazole buffer. The Pb2+ ion improves the yield of longer oligomers and changes substantially the distribution of linkage isomers. The Pb2+ ion greatly improves the yield of longer oligomers obtained from G and ImpGpG on a poly(C) template. The self-condensation of ImpGpG in a 2, 6-lutidine buffer is much less efficient than in a 1-methylimidazole buffer. The Zn2+ greatly increases the yield of products from the [3'-5']-linked dimer, but fails to catalyze the formation of long oligomers from the [2'-5']-linked dimer. The bonds formed in the Zn2+-catalyzed self-condensation of ImpG3pG on poly(C) are mainly [3'-5'] linked. PMID- 6268801 TI - Beet yellow stunt virus in the phloem of Sonchus oleraceus L. PMID- 6268802 TI - Characterization of AKR murine leukemia virus sequences in AKR mouse substrains and structure of integrated recombinant genomes in tumor tissues. AB - A specific cDNA probe of AKR murine leukemia virus (AKR-MLV) was prepared to detect AKR-MLV sequences in normal and tumor tissues in a variety of AKR mouse substrains. AKR strains contained up to six endogenous AKR-MLV genomes. All substrains tested had one AKR-MLV locus in common, and closely related substrains had several proviruses integrated in an identical site. Virus-induced tumors in the AKR/FuRdA and AKR/JS strains showed a reintegration pattern of AKR-MLV sequences unique for the individual animal, suggesting a monoclonal origin for the outgrown tumors. An analysis of tumor DNAs from the AKR/FuRdA and AKR/JS substrains with restriction enzymes cleaving within the proviral genome revealed a new EcoRI restriction site and BamHI restriction site not present in normal tissues. The positions of these sites corresponded both with cleavage sites of EcoRI and BamHI in integrated Moloney recombinants and with the structure of isolated AKR mink cell focus-forming viruses. All tumors analyzed to data contain nearly identical integrated recombinant genomes, suggesting a causal relationship between the formation of recombinants and the leukemogenic process. PMID- 6268803 TI - Evidence that there exist four classes of RNA tumor viruses which encode proteins with associated tyrosine protein kinase activities. AB - The transforming protein of Rous sarcoma virus, p60src, the Abelson virus protein, p120, and the Y73 virus protein, p90, all have associated tyrosine protein kinase activities in vitro. Possible structural homology between these functionally related proteins was investigated by two-dimensional analysis of both methionine-containing and phosphate-containing tryptic peptides derived from biosynthetically labeled proteins. Marked differences were found between the maps of both [35S]methionine-labeled and 32P-labeled tryptic peptides. This suggests that the transforming gene of Rous sarcoma virus and the putative transforming genes of Abelson virus and Y73 virus are different. In addition, each of these genes has been shown previously to be unrelated to the putative transforming gene of Fujinami sarcoma virus, another virus which encodes a protein with associated tyrosine protein kinase activity. Therefore, it appears that there exist at least four distinct classes of functionally related RNA tumor viruses. Analysis of phosphorylated tryptic peptides did, however, reveal homology between one of the two phosphotyrosine-containing tryptic peptides of p90 of Y73 virus and the single phosphotyrosine-containing tryptic peptide of p60src of Rous sarcoma virus. Comigration of these two peptides in several different buffers and the identical mobility of their phosphorylated cleavage products after secondary digestion with protease V8 of Staphylococcus aureus indicated that p60src and p90 contain an identical site of tyrosine phosphorylation in vivo. The results are discussed with respect to the evolution of RNA tumor viruses which encode proteins with associated tyrosine protein kinase activities and the limitations of analysis of detecting homology between genes by both molecular hybridization and peptide mapping. PMID- 6268804 TI - Mapping of alterations in noninfectious proviruses of spleen necrosis virus. AB - Ten recombinant lambda phage containing proviruses of spleen necrosis virus (SNV) were previously obtained. Six of the proviruses are infectious and four are not infectious in infectious DNA assays. In this paper, we show that these noninfectious proviruses are not infectious because of alterations in the viral DNA. We constructed recombinants between infectious and noninfectious proviruses and tested these recombinants in an infectious DNA assay. In addition, we carried out cotransfection of a noninfectious provirus with a restriction endonuclease generated fragment of viral DNA. The alterations in the viral DNA resulting in lack of infectivity were mapped to regions of viral DNA of 1 to 2 kilobase pairs. These results and other biochemical data indicate that alterations in retrovirus proviruses occur at a high frequency. PMID- 6268805 TI - Fine-structure mapping of herpes simplex virus type 1 temperature-sensitive mutations within the short repeat region of the genome. AB - Cloned herpes simplex virus type 1 (HSV-1) DNA fragments were used to fine structure map the temperature-sensitive (ts) lesions from four mutants, ts T, D, c75, and K, by marker rescue. These mutants all overproduced immediate-early viral polypeptides at the nonpermissive temperature. Although one of these viruses, ts K, gave a more restricted infected-cell polypeptide profile under these conditions than the other three, no complementation was detected between pairwise crosses of these mutants in the yield test. Recombination, however, was obtained between all mutant pairs except ts T and D. In physical mapping experiments, ts+ virus was recovered from cells coinfected with DNA of ts T, D, or c75 and BamHI fragment k from wild-type strain 17 HSV-1 DNA cloned in pAT153, whereas ts K was rescued by cloned HSV-1 BamHI-y. Both of these cloned DNA fragments contained sequences from the short repeat region of the HSV-1 genome. The ts mutations were more precisely mapped by marker rescue, using restriction enzyme fragments within BamHI-k and -y from cloned DNA. The smallest fragment able to rescue a mutant was 320 base pairs long. The order of the four mutations derived from these studies was consistent with the assignment by genetic recombination. All four lesions mapped within the coding sequences of the immediate-early polypeptide Vmw IE 175 (ICP4) which lie outside the "a" sequence. The results showed that mutations in different regions of the gene encoding Vmw IE 175 could produce similar phenotype effects at the nonpermissive temperature. PMID- 6268806 TI - Molecular cloning of B- and N-tropic endogenous BALB/c murine leukemia virus circular DNA intermediates: isolation and characterization of infectious recombinant clones. AB - The unintegrated closed circular DNA intermediates from B- and N-tropic endogenous BALB/c murine leukemia virus (MuLV) were isolated from acutely infected mouse fibroblasts and cleaved at their unique HindIII sites. The linearized B- and N-tropic MuLV DNAs were then inserted in lambda vector Charon 21A and cloned. Seventeen B-tropic and ten N-tropic recombinants were analyzed. The viral insert of these 27 MuLV recombinants could be grouped into 3 classes. The first class included permuted full-length molecules of 8.8 kilobase pairs (kbp) having two long terminal repeats (LTR) (0.55 kbp) mixed with 8.25-kbp molecules. The second class included 8.25-kbp molecules which harbored only one LTR copy. The third class of inserts was made of molecules with deletions of various lengths (0.1 to 3 kbp). These deletions were localized by restriction enzyme analysis. Significantly more deletions were observed in N-tropic than in B tropic recombinants, although these two genomes isolated from acutely infected cells seemed to differ only by the absence of a 70-base-pair (bp) sequence in the N-tropic LTR. The biological activity of each of the recombinants of the first and second classes was assayed by transfection on NIH/3T3 cells. Two recombinants, one B-tropic (lambda B-16) and one N-tropic (lambdaN-20) were found to be infectious. Both were able to give rise to replication-competent MuLV which could form large XC plaques and had kept the tropism of its progenitor. Like its progenitor in vivo DNA, lambdaN-20-cloned DNA lacked a 70-bp sequence in its unique LTR. The emerging N-tropic MuLV after transfection with lambdaN-20 was used to acutely infect NIH/3T3 cells. The viral DNA intermediates isolated were now found to have two LTR copies. They had also acquired a 70-bp sequence in each LTR. The acquisition or loss of this 70-bp sequence did not seem to affect the replication, the XC plaque formation, or the tropism of the virus. PMID- 6268808 TI - Integrated polyoma genomes in inducible permissive transformed cells. AB - Using the approach described by Botchan, Topp, and Sambrook (Cell 9:269-287, 1976), we analyzed the organization of the integrated viral sequences in five clonal isolates from the same permissive, inducible cell line (Cyp line) transformed by the tsP155 mutant of polyoma virus. In all five clones, viral sequences were found that could be assigned to a common integration site, as they were joined to the cellular DNA in the same fashion in every instance. However, the sequences comprised between these points differed markedly from clone to clone, as if cell propagation had been accompanied by amplification or recombination or both within the viral insertion. When the clones were compared, no correlation could be found between the abundance, or the organization, of the integrated viral sequences and the amount, or the nature, of the free viral DNA molecules produced during induction. Altogether, our findings suggest that specific events, occurring during either the excision or the subsequent replication of the integrated viral sequences, are responsible for the predominant production of nondefective viral DNA molecules by permissive transformed cells, such as Cyp cells. PMID- 6268807 TI - Epstein-Barr virus membrane antigens: characterization, distribution, and strain differences. AB - The Epstein-Barr virus (EBV)-associated membrane antigen polypeptides (350,000, 220,000, 140,000, and 85,000 daltons) are recognized by a rabbit anti-EBV serum and are present on the plasma membranes of producer cell lines, as we demonstrated previously. In this report, we show that these polypeptides are present on intact virus particles. Subcellular fractionation revealed that these antigens are distributed throughout the cell, except for the 85,000-dalton protein, which was poorly represented in the nuclear fraction. In addition, an EBV-associated protein of 160,000 daltons, which comigrates with a major component of the viral capsid, was detected in the cytoplasmic and nuclear fractions. The immunoprecipitation patterns of 13 different EBV isolates were similar, with two exceptions. First, the 350,000- and 220,000-dalton polypeptides from marmoset cell lines had slightly larger molecular sizes than the corresponding polypeptides from human cell lines. Second, B95-8 virus and B95-8 derived human and marmoset cell lines contained little of the 220,000-dalton protein; however, 883L, the human parent line of B95-8, has a normal amount of the 220,000-dalton protein. Thus, the B95-8 strain of EBV appears to be a structurally defective variant. We have not observed any variation in protein patterns associated with different EBV disease states. The 350,000-, 220,000-, and 85,000-dalton polypeptides were shown to be glycoproteins by incorporation of [3H]mannose and [3H]glucosamine and to contain N-asparagine-linked glycosyl groups by their sensitivity to tunicamycin. To simplify future work, the following nomenclature for these EBV-associated polypeptides is suggested: 350,000 (gp350), 220,000 (gp220), 160,000 (p160), 140,000 (p140), and 85,000 (gp85). PMID- 6268809 TI - Inducible permissive cells transformed by a temperature-sensitive polyoma virus: superinfection does not allow excision of the resident viral genome. AB - After exposure of mouse embryo cells to the early temperature-sensitive mutant tsP155 of polyoma virus (Py), a transformed cell line (Cyp line) that can be readily induced to synthesize Py by transfer to 33 degrees C was isolated at 39 degrees C (7). Virus production and synthesis of free viral DNA occurring after temperature shiftdown or superinfection with wild-type Py or both were studied in several clonal isolates of the Cyp cell line. Measurements of virus yields indicated that, although some could be induced more effectively than others, all cell clones behaved as highly permissive when subjected to superinfection. We analyzed the origin of free viral DNA accumulating in the superinfected cultures, taking advantage of (i) the unique physical properties of the low-molecular weight DNA which, in the case of one of the Cyp clones, accumulates during temperature shiftdown, and (ii) the differences between resident and superinfecting viral genomes in their susceptibilities towards restriction endonucleases. At 33 degrees C, both viral genomes were found to accumulate in all clones studied whereas in the case of the clones with lower inducibility, the replication of the resident genome appeared to be enhanced by superinfection. At 39 degrees C, however, accumulation of the superinfecting genome was not accompanied by that of the resident genome, unless it had already been initiated before superinfection. These findings demonstrate that, when routinely cultivated at 39 degrees C, Cyp cells contain few viral DNA molecules readily available for autonomous replication and that, upon transfer to 33 degrees C, therefore, excision must first take place before the resident genome can accumulate as free viral DNA. Our findings also suggest that, unlike the P155 gene product provided by the resident viral genome upon induction, the allelic gene product supplied by the superinfecting genome may be less effective in triggering excision than in promoting replication. PMID- 6268810 TI - Purification and translation of murine mammary tumor virus mRNA's. AB - We have studied the functions of the intracellular RNAs of mouse mammary tumor virus (MMTV) by purification and translation in vitro. Two major size classes of MMTV RNA, 35S and 24S RNA, were isolated from MMTV-infected rat (XC) cells and cultured mammary tumor cells by preparative hybridization of whole cell or polyadenylated RNA to cloned MMTV DNA covalently bound to chemically activated paper disks (diazobenzyloxymethyl paper). Genomic-length (35S) RNA was prepared free of 24S RNA by rate zonal sedimentation in sucrose gradients. Experiments using [3H]uridine-labeled cellular RNA indicated that the preparative annealing method was highly specific and capable of effecting a 300-fold enrichment for viral RNA; the recovered RNA appeared to be intact under denaturing conditions and directed synthesis of full-length gag and env polypeptides in vitro. The products of in vitro translation were identified by gel mobility, immunoprecipitation tests with antisera against gag and env products, and partial digestion with Staphylococcus V8 protease. The 35S RNA species directed synthesis of several gag-related polypeptides, including three previously reported in extracts of infected cells; 24S RNA directed synthesis of two polypeptides closely related to env proteins from infected cells. Therefore, 35S RNA includes mRNA's for gag and gag-pol, whereas 24S RNA is the mRNA for env. These results help establish the position of env on the physical map of the MMTV genome and bear upon the coding potential of the genome. PMID- 6268811 TI - Both strands of polyoma DNA are replicated discontinuously with ribonucleotide primers in vivo. AB - Nascent polyoma DNA molecules were isolated after pulse-labeling of infected murine 3T6 cells with [3H]thymidine. The extent of digestion of these DNA molecules by spleen exonuclease was increased by exposure to alkali or RNase, suggesting that ribonucleotides were present at or near the 5' terminal of the newly synthesized pieces of DNA. Intermediates shorter than 300 nucleotides were hybridized to the separated strands of restriction enzyme fragments of the polyoma genome: 2.5 to 3-fold more radioactivity was found in the strand whose synthesis is necessarily discontinuous (the lagging strand) than in the strand whose synthesis is potentially continuous (the leading strand) than in the strand whose synthesis is potentially continuous (the leading strand). Separation of the strands of [5'-32P]DNA molecules showed that the excess [3H]thymidine in lagging strand molecules was not simply the result of an increased number of molecules. Therefore, assuming equivalent efficiencies of labeling, lagging-strand pieces must be slightly longer than those with leading-strand polarity. The presence of ribonucleotides on the 5' termini of molecules with both leading- and lagging strand polarity was demonstrated by (i) release of 32P-ribonucleoside diphosphates upon alkaline hydrolysis of [5'-32P]DNA separated according to replication polarity and (ii) the change in the degree of self-annealing of nascent molecules upon preferential degradation of DNA molecules possessing initiator RNA moieties by spleen exonuclease. We conclude that replication of polyoma DNA in vivo occurs discontinuously on both sides of the growing fork, using RNA as the major priming mechanism. PMID- 6268812 TI - Recombinants between temperature-sensitive mutants of rauscher murine leukemia virus and BALB:virus-2: genetic mapping of the Rauscher murine leukemia virus genome. AB - Recombinant viruses were generated in tissue culture between Rauscher murine leukemia virus (MuLV) temperature-sensitive (ts) mutants restricted at different steps in virus replication and a mouse endogenous xenotropic virus, BALB:virus-2. Mutants used included ts 28, a late mutant which releases noninfectious viruses at 39 degrees C, and ts 29, a double mutant with a ts lesion in its reverse transcriptase and a late block affecting virus budding. Immunological typing of the translational products of clonal recombinant viruses made it possible to establish their partial genetic maps and localize regions of the viral genome affected by different ts lesions. Recombinants involving Rauscher MuLV ts 28 invariably contained BALB-virus-2 p15, p12, and p30 proteins, localizing the late defect in replication by this mutant to the 5' moiety of the viral gag gene. All ts 29-derived recombinants contained the entire BALB:virus-2 gag and pol genes. Substitution of the pol gene is in agreement with the reported thermolability of Rauscher MuLV ts 29 reverse transcriptase (Tronick et al., J. Virol. 16:1476 1482, 1975). Substitution of the gag gene suggests that internal structural proteins are actively involved in the virus budding processing. Rauscher MuLV recombinants were used to establish the genetic map of the Rauscher MuLV genome by T1 oligonucleotide fingerprinting analysis. Detection of Rauscher MuLV T1 oligonucleotides in representative recombinant viruses, whose protein phenotypes were established by immunological techniques, permitted their assignment to specific regions of the viral genome. The genetic map of Rauscher MuLV generated in these studies should be useful for identifying and characterizing the viral gene(s) involved in leukemogenesis. PMID- 6268813 TI - 5'-terminal nucleotide noncoding sequences of retroviruses: relatedness of two old world primate type C viruses and avian spleen necrosis virus. AB - Computer-assisted comparison of the 5'-terminal regions of mammalian type C viruses serves as a useful model of evolutionary divergence of noncoding nucleic acid sequences. It has led to the concept that regions of conserved nucleic acid sequences, the slowly divergent sequences, contain signals of translational, transcriptional, or integrative significance. Interspersed among the conserved regions are rapidly divergent sequences in which base changes, insertions, and deletions are especially prevalent. In the present study, CPC-1, a type C virus isolated from Colobus polykomos, was shown to be related to another Old World type C monkey virus, endogenous stump-tailed monkey virus, MAC-1, by analysis of their 5'-terminal nucleotide sequences. The 5'-terminal regions of CPC-1 and MAC 1 showed a 76% nucleotide correspondence and were of similar lengths, 132 and 127 nucleotides, respectively. Previous strong-stop analyses of other type C viruses have defined two subgroups: (i) Rauscher murine leukemia virus and gibbon ape leukemia virus and (ii) baboon endogenous virus and endogenous cat virus RD114. Based on the present sequence analysis of their 5'-terminal sequences, CPC-1 and MAC-1 formed a third subgroup. Computer-assisted comparison of the 5'-terminal sequences of CPC-1 and MAC-1 to the previously reported sequence of avian spleen necrosis virus (SNV) (Shimotohno et al., Nature [London] 285:550-554, 1980) showed SNV to be a member of that subgroup of mammalian type C viruses. Consistent with the inclusion of SNV in this subgroup of mammalian type C viruses, SNV was distantly related to other mammalian type C viruses. Interestingly, the SNV 5'-terminal sequences showed no significant evolutionary relationship by these criteria to the avian leukemia and sarcoma viruses. CPC-1, MAC-1, and SNV contained conserved regulatory signals in similar positions in their 5'-terminal RNA sequences analogous to those observed in other mammalian type C retroviruses. These sequences included the canonical AAUAAA sequence, a palindrome, a putative ribosome binding site, and an integration site. Some of these highly conserved subsequences were common to 3'- and 5'-terminal noncoding sequences of nonviral eucaryotic mRNA's (Efstratiadis et al., Cell 21:653-668, 1980). Thus, analysis and comparison of 5'-terminal nucleotide sequences have been useful in defining common functional signals and in extending the matrix of relationships among retroviruses. PMID- 6268814 TI - Cessation of reentry of simian virus 40 DNA into replication and its simultaneous appearance in nucleoprotein complexes of the maturation pathway. AB - Newly synthesized SV40 DNA is used as a template for further DNA synthesis (reenters replication) or as a substrate in the assembly of virions (maturation pathway). The time courses of reentry into replication and progression along the maturation pathway were both determined on identical samples. DNA, synthesized during a 20-min pulse, reentered replication over a period of several hours and then was removed from the pool of molecules available for replication. The cessation of reentry coincided with the maturation of this DNA from the chromatin form to previrion and virion forms. More reentry and less maturation was observed at 24 h postinfection than at 42 h postinfection. The data are consistent with the hypothesis that the factor(s) responsible for cessation of reentry is also responsible for initiation of the maturation pathway. PMID- 6268815 TI - Immunoelectron microscopic study on interactions of noninfectious sendai virus and murine cells. AB - The early interactions of LLC-MK2 cell-grown noninfectious Sendai virus and a murine cell line, P815 mastocytoma ascitic cells, were studied by electron microscopy, using the ferritin-conjugated antibody technique with anti-virus glycoprotein serum. For comparison, the interactions of egg-grown infectious Sendai virus with the same cells were also examined. When noninfectious virus was adsorbed to the cells in the cold, the cell membranes become partially invaginated at the site of contact of adsorbed virions, but ferritin-conjugated antibodies did not penetrate into the areas of envelope-cell membrane association. This pattern of virus attachment was similar to that of infectious virus attachment. Upon subsequent incubation at 37 degrees C, most of the adsorbed noninfectious virions were taken into cytoplasmic vesicles and then degraded, although a few virions remained attached to the cell membrane. No evidence of fusion of envelopes of noninfectious virions was obtained. On the other hand, envelopes of infectious virions fused with the cell membrane, and the transferred viral antigens diffused on the cell surfaces and then decreased in number. PMID- 6268816 TI - Chromosomal localization of three endogenous retrovirus loci associated with virus production in White Leghorn chickens. AB - Proposed mechanisms for the generation of endogenous retrovirus loci have been examined by determining the chromosomal distribution of these loci by means of in situ hybridization. Unlike the clustering on chromosome 1 of five endogenous retrovirus loci associated with the gs- chf- phenotype A. Tereba and S. M. Astrin, submitted for publication), three loci associated with endogenous retrovirus production (V+ phenotype) were located on three separate chromosomes. ev2, which codes for the prototype endogenous RAV-0 genome in line 7(2) chickens, was localized near the middle of the long arm of chromosome 2, ev7, coding for a noninfectious, inducible genome present in line 15B chickens, was located near the end of the long arm of the Z chromosome. A third V+ locus, designated ev14, was detected near the middle of chromosome 3. This arrangement of V+ loci is consistent with an integration mechanism employing randomly distributed integration sites in the chicken genome. In addition, these data provide evidence suggesting that the gs- chf- -associated loci may have been generated by a different mechanism. PMID- 6268817 TI - Role of the vesicular stomatitis virus matrix protein in maintaining the viral nucleocapsid in the condensed form found in native virions. AB - Vesicular stomatitis virus was extracted with 60 mM octylglucoside in the absence of salts and in the presence of 0.5 M NaCl. The resulting extracted virus particles were examined by electron microscopy, and the proteins present were identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Extraction in the absence of salts yielded subviral structures which we cell "skeletons" as originally suggested by Cartwright et al. (J. Gen. Virol. 7:19-32, 1970). The skeletons contained the viral N, M, and L proteins, but they lacked the glycoprotein (G) entirely. Morphologically, the skeletons resembled intact vesicular stomatitis virus but they were slightly longer and smaller in diameter. Like native vesicular stomatitis virus, skeletons were found to have lateral striations spaced 5.0 to 6.0 nm apart along the length of the structure. In contrast to extraction in the absence of NaCl, extraction of vesicular stomatitis virus with 60 mM octylglucoside in the presence of 0.5 M NaCl yielded highly extended viral nucleocapsids in which N was the predominant protein; no M or G proteins could be detected. These results support the view that the M protein is involved in maintaining the nucleocapsid in the compact form found in native virions. PMID- 6268818 TI - Polyoma virus infection of retinoic acid-induced differentiated teratocarcinoma cells. AB - The mouse teratocarcinoma stem cell line, F9, becomes permissive for productive polyoma infection upon treatment with retinoic acid. Through the use of M13 polyoma recombinant single-stranded DNA probes, spliced and unspliced early viral RNA were detected after polyoma infection of retinoic acid-treated and untreated F9 cultures. PMID- 6268819 TI - Isolation of monoclonal antibodies against avian oncornaviral protein p19. AB - For the production of monoclonal antibodies against pp60src and the gag precursor protein Pr76gag, the spleens of mice bearing tumors that had been induced by avian sarcoma virus Schmidt-Ruppin D-transformed cells were used. One hybridoma culture produced antibodies that were directed against the p19 portion of the gag precursor. However, no antibodies directed against pp60src could be detected in any of the hybridoma supernatants. The anti-p19-producing hybridoma culture was cloned twice in soft agar, and a stable clone was used for the production of high titer ascites fluid in mice. The monoclonal antibodies belonged to the immunoglobulin G subclass 2b. The antibodies precipitated Pr76gag and the processed virion-associated p19, as well as the 75,000-molecular-weight gag fusion protein from avian erythroblastosis virus-transformed bone marrow cells. Also, viral ribonucleoprotein complexes were specifically precipitable, indicating that they contain p19 molecules. PMID- 6268820 TI - Regulation of expression of cloned bacteriophage T4 late gene 23. AB - The parameters governing the activity of the cloned T4 gene 23, which codes for the major T4 head protein, were analyzed. Suppressor-negative bacteria carrying wild-type T4 gene 23 cloned into plasmid pCR1 or pBR322 were infected with T4 gene 23 amber phage also carrying mutations in the following genes: (i) denA and denB (to prevent breakdown of plasmid DNA after infection) and (ii) denA, denB, and, in addition, 56 (to generate newly replicated DNA containing dCMP) and alc/unf (because mutations in this last gene allow late genes to be expressed in cytosine-containing T4 DNA). Bacteria infected with these phage were labeled with (14)C-amino acids at various times after infection, and the labeled proteins were separated by one-dimensional gel electrophoresis so that the synthesis of plasmid coded gp23 could be compared with the synthesis of other, chromosome-coded T4 late proteins. We analyzed the effects of additional mutations that inactivate DNA replication proteins (genes 32 and 43), an RNA polymerase-binding protein (gene 55), type II topoisomerase (gene 52), and an exonuclease function involved in recombination (gene 46) on the synthesis of plasmid-coded gp23 in relation to chromosome-coded T4 late proteins. In the denA:denB:56:alc/unf genetic background, the phage chromosome-borne late genes followed the same regulatory rules (with respect to DNA replication and gp55 action) as in the denA:denB genetic background. The plasmid-carried gene 23 was also under gp55 control, but was less sensitive than the chromosomal late genes to perturbations of DNA replication. Synthesis of plasmid-coded gp23 was greatly inhibited when both the type II T4 topoisomerase and the host's DNA gyrase are inactivated. Synthesis of gp23 was also substantially affected by a mutation in gene 46, but less strongly than in the denA:denB genetic background. These observations are interpreted as follows. The plasmid-borne T4 gene 23 is primarily expressed from a late promoter. Expression of gene 23 from this late promoter responds to an activation event which involves some structural alteration of DNA. In these respects, the requirements for expressing the plasmid-borne gene 23 and chromosomal late genes are very similar (although in the denA:denB:56:alc/unf genetic background, there are significant quantitative differences). For the plasmid-borne gene 23, activation involves the T4 gp46, a protein which is required for DNA recombination. However, for the reasons presented in the accompanying paper (Jacobs et al., J. Virol. 39:31-45, 1981), we conclude that the activation of gene 23 does not require a complete breakage-reunion event which transposes that gene to a later promoter on the phage chromosome. Ways in which gp46 may actually be involved in late promoter activation on the plasmid are discussed. PMID- 6268821 TI - Removal of the genome-linked protein of foot-and-mouth disease virus by rabbit reticulocyte lysate. AB - Rabbit reticulocyte lysate cleaves the genome-linked protein VPg from foot-and mouth disease virus (FMDV) RNA. This activity could be reliably monitored since removal of the protein resulted in a change in migration in polyacrylamide gels of the small specific 5' and fragment of the RNA (S fragment). The unlinking activity cleaved the bond between the tyrosine residue of VPg and the RNA to leave a 5' phosphate on the RNA. The 5' sequence of the RNA from which VPg had been removed by rabbit reticulocyte lysate was the same as that of FMDV mRNA isolated from infected cells. VPg released from the RNA was rapidly degraded by the rabbit reticulocyte lysate to material which eluted with the inclusion volume of a Sepharose 6B column and partitioned to the aqueous phase during phenol extraction. The unlinking activity was inhibited by heating the lysate to 56 degrees C, by sodium dodecyl sulfate (SDS), EDTA, and Zn2+ ions but was unaffected by reducing agents, a translation inhibitor, and a number of protease and RNase inhibitors. PMID- 6268822 TI - Amplification of a short nucleotide sequence in the repeat units of defective herpes simplex virus type 1 Angelotti DNA. AB - It has been shown earlier that the reiterated regions TRS and IRS bracketing the Us segment of herpes simplex virus type 1 Angelotti DNA are heterogeneous in size by stepwise insertion of one to six copies of a 550-base-pair nucleotide sequence. Considerably higher amplification of this sequence was observed in defective viral DNA: up to 14 copies were detected to be inserted in the repeat units of a major class of defective herpes simplex virus type 1 Angelotti DNA, dDNA1, which originated from noncontiguous sites located in UL and the inverted repeats of the S component of the parental genome. Physical maps were established for the cleavage sites of KpnI, PstI, XhoI, and BamHI restriction endonucleases on the repeats of dDNA1. The map position of the insertion sequence was determined. It was demonstrated that the amplified inserts were not distributed at random among or within the repeats. A given total population of dDNA1 molecules consisted of different homopolymers, each of which contained a constant number of inserts in all of its repeats. Assuming that a rolling-circle mechanism is involved in the generation of full-length defective herpes simplex virus type 1 Angelotti DNA from single repeat units, these data suggest that the 550-base pair sequence is amplified in the repeats before the replication process. PMID- 6268823 TI - Structural changes in BHK cell plasma membrane caused by the binding of vesicular stomatitis virus. AB - Spin label electron spin resonance techniques using a nitroxide derivative of stearic acid were used to detect changes in plasma membrane structure caused by the binding of vesicular stomatitis virus (VSV) to cell plasma membranes of intact BHK-21 cells. The results indicate that binding of VSV to cell surface receptors causes an increase in the observed rigidity of the plasma membrane lipid bilayer. This change in membrane structure, which appears to be caused by the cross-linking of receptors in the plane of the plasma membrane, could be prevented by treating the cells with colchicine before addition of virus and could be reversed by treating the cells with colchicine after addition of virus. Cells treated with a monovalent, water-soluble derivative of VSV G-protein (Gs) did not show an increase in plasma membrane bilayer rigidity. However, addition of anti-VSV G-protein immunoglobulin G to cells pretreated with G8 caused an increase in plasma membrane bilayer rigidity. This increased rigidity could also be reversed by the addition of colchicine. Fluorescence microscopy was used to determine the distribution of fluorescein-labeled VSV particles on the cell surface after addition of virus. Approximately 30 min after addition of virus, discrete areas on the cell surface showed fluorescent staining, which coalesced to apical regions of the cell after approximately 40 min. PMID- 6268824 TI - Identification of promoter-proximal oligonucleotides and a unique dinucleotide, pppGpC, from in vitro transcription products of vesicular stomatitis virus. AB - The oligonucleotides synthesized by purified vesicular stomatitis virus in vitro in the absence of one or more ribonucleoside triphosphate precursors have been studied. The oligonucleotides contained the 5'-terminal sequences of the leader RNA and one or more mRNA's. The promoter-proximal oligonucleotides lacked 5' terminal cap structure and contained triphosphate A. These results suggest that the RNA polymerase is located at multiple promoter sites on the genome RNA from where it initiates transcription. The capping reaction appears to occur subsequently during RNA chain elongation. We have also demonstrated that a unique dinucleotide, pppGpC, of presently unknown function is synthesized in vitro in large amounts during RNA synthesis or in the presence of GTP and CTP only. PMID- 6268825 TI - Alterations to controls of cellular DNA synthesis by adenovirus infection. AB - Human adenovirus type 5 and temperature-sensitive mutants ts36, ts37, and ts125 induced cellular DNA synthesis in quiescent rodent cells at both permissive and nonpermissive temperatures. Cellular DNA synthesis induced by adenovirus type 5 or by serum required protein synthesis for both initiation and continuation, whereas viral DNA synthesis was not dependent upon continued protein synthesis once it was initiated. Both cellular and viral DNA replication was induced in adenovirus type 5-infected cells in the presence of dibutyryl cyclic AMP at concentrations which inhibited induction by serum which suggested that some of the controls of DNA synthesis in serum-treated and virus-infected cells are different. After adenovirus infection of quiescent cells, there was a decrease in the number of cells with G1 DNA content and an increase in cells with G2 diploid and greater DNA contents. Thus, adenovirus type 5 induces a complete round of cellular DNA replication, but in some cells, it induces a second round without completion of a normal mitosis. These results suggest that adenovirus type 5 is able to alter cell growth cycle controls in a way which may be related to its ability to transform cells. PMID- 6268826 TI - Poliovirus morphogenesis. I. Identification of 80S dissociable particles and evidence for the artifactual production of procapsids. AB - The current model of poliovirus morphogenesis postulates a fundamental role for procapsid, 80S shells that, upon interaction with viral RNA and subsequent proteolytic cleavage, give rise to complete virus particles. Although 80S sedimenting particles can, indeed, be isolated from cytoplasmic extracts of infected cells, their physical properties differ from those reported for procapsids. Far from being stable structures, they can be dissociated by pH 8.5 and 0.1% sodium dodecyl sulfate into slower-sedimenting subunits. The reasons for this discrepancy were investigated, and two main modalities leading to the appearance of procapsids in vitro were identified. The first involves a temperature-mediated conversion of dissociable 80S particles into stable 80S procapsids, and the second involves the self-assembly of endogenous 14S subunits, also primed by an increase in the temperature of cytoplasmic extracts. PMID- 6268827 TI - Phosphorylation of ribosomal proteins in hamster fibroblasts infected with pseudorabies virus or herpes simplex virus. AB - In BHK cells infected with pseudorabies virus, there was a substantial increase in the phosphorylation of ribosomal protein S6. This increase occurred between 2 and 4 h after infection and persisted at least until 9 h. We estimated that in mock-infected cells S6 contained, on an average, one phosphate group per protein chain, whereas in infected cells this rose to between four and five phosphate groups per protein chain. A second ribosomal protein, either S16 or S18, was also phosphorylated after infection. No increase in cyclic AMP was found at the time of phosphorylation. We also found an increased phosphorylation of S6 in herpes simplex virus-infected BHK cells. PMID- 6268829 TI - Enhanced mutability associated with a temperature-sensitive mutant of vesicular stomatitis virus. AB - Temperature-sensitive (ts) mutant tsD1 of vesicular stomatitis virus, New Jersey serotype, is the sole representative of complementation group D. Clones derived from this mutant exhibited three different phenotypes with respect to electrophoretic mobility of the G and N polypeptides of the virion in sodium dodecyl sulfate-polyacrylamide gel. Analysis of non-ts pseudorevertants showed that none of the three phenotypes was associated with the temperature sensitivity of mutant tsD1. Additional phenotypes, some also involving the NS polypeptide, appeared during sequential cloning, indicating that mutations were generated at high frequency during replication of tsD1. Furthermore, mutations altering the electrophoretic mobility of the G, N, NS, and M polypeptides were induced in heterologous viruses multiplying in the same cells as tsD1. These heterologous viruses included another complementing ts mutant of vesicular stomatitis virus New Jersey and ts mutants of vesicular stomatitis virus Indiana and Chandipura virus. Complete or incomplete virions of tsD1 appeared to be equally efficient inducers of mutations in heterologous viruses. Analysis of the progeny of a mixed infection of two complementing ts mutants of vesicular stomatitis virus New Jersey with electrophoretically distinguishable G, N, NS, and M proteins yielded no recombinants and excluded recombination as a factor in the generation of the electrophoretic mobility variants. In vitro translation of total cytoplasmic RNA from BHK cells indicated that post-translational processing was not responsible for the aberrant electrophoretic mobility of the N, NS, and M protein mutants. Aberrant glycosylation could account for three of four G protein mutants, however. Some clones of tsD1 had an N polypeptide which migrated faster in sodium dodecyl sulfate-polyacrylamide gel than did the wild type, suggesting that the polypeptide might be shorter by about 10 amino acids. Determination of the nucleotide sequence to about 200 residues from each terminus of the N gene of one of these clones, a revertant, and the wild-type parent revealed no changes compatible with synthesis of a shorter polypeptide by premature termination or late initiation of translation. The sequence data indicated, however, that the N protein mutant and its revertant differed from the parental wild type in two of the 399 nucleotides determined. These sequencing results and the phenomenon of enhanced mutability associated with mutant tsD1 reveal that rapid and extensive evolution of the viral genome can occur during the course of normal cytolytic infection of cultured cells. PMID- 6268828 TI - Mammary tumor virus proviral DNA in normal murine tissue and non-virally induced mammary tumors. AB - The Southern DNA filter transfer technique was used to study the involvement of the endogenous mouse mammary tumor virus (MMTV) in the development of mammary tumors of nonviral etiology. The presence of extra MMTV proviruses in the genomes of these non-virally induced mammary tumors would indicate an integration of the provirus of an activated endogenous MMTV. Acquisition of MMTV proviruses did not seem to be an absolute requirement for the development of hormone or carcinogenically induced mammary tumors in strain BALB/c nor for hormone-induced mammary tumors in mouse strains 020, C57BL, and C3Hf. In some hormone-induced mammary tumors we did observe extra MMTV proviruses in submolar quantities, indicating that reintegration may occasionally occur and that only a part of the tumor cells acquired new MMTV DNA information. Hormone-dependent and -independent primary mammary tumors of the mouse strain GR, which are controlled by the Mtv-2 mammary tumor induction gene, all acquired extra MMTV proviruses. Most of these extra MMTV proviral-DNA-containing fragments appeared present in submolar quantities, suggesting that only part of the tumor cells acquired extra MMTV proviral information. These findings indicate that the initially transformed mammary gland cells of non-virally induced mammary tumors do not necessarily acquire extra MMTV proviral DNA information, in contrast to the MMTV-induced mammary tumors, in which all tumor cells contain extra MMTV DNA information. PMID- 6268830 TI - XbaI, PstI, and BglII restriction enzyme maps of the two orientations of the varicella-zoster virus genome. AB - Cleavage of varicella-zoster virus DNA with the restriction endonucleases PstI, XbaI, and BglII resulted in 18, 22, and 20 fragments, respectively. Based on the molecular weights and molarities of these fragments, a molecular weight of 84 x 10(6) could be calculated for the varicella-zoster virus genome. In both the XbaI and the BglII patterns, four 0.5 M fragments were identified. The arrangement of the fragments was determined by molecular hybridization techniques, and the terminal fragments were identified by lambda exonuclease digestion. The 0.5 M fragments, of which two were located at the same terminus of the genome, contained repeated sequences: one terminally and one inverted internally. These results were in agreement with the existence of two equimolar subpopulations of the varicella-zoster virus genome, differing in the relative orientation of a short region of unique sequences. This region was bounded by the repeated sequences. From the molecular weights of the submolar fragments, a maximal molecular weight of 5 x 10(6) for the repeated region and a minimal molecular weight of 3.5 x 10(6) for the short unique sequence could be calculated. PMID- 6268831 TI - Synthesis of subgenomic mRNA's of mouse hepatitis virus is initiated independently: evidence from UV transcription mapping. AB - The target sizes of the templates for the synthesis of the genome-sized RNA and the six subgenomic RNAs found in cells infected with mouse hepatitis virus strain A59 were determined by UV transcription mapping. Infected Sac(-) cells were irradiated at 6 h postinfection, the time when virus-specific RNA synthesis starts to increase exponentially. The effect of increasing UV doses on the synthesis of the individual RNAs was determined by quantitation of these RNAs after separation by agarose gel electrophoresis. The UV target sizes calculated for the templates were almost identical to the physical sizes of the RNAs. The results of these experiments seem to exclude the possibility that the subgenomic RNAs are processed or spliced from a common precursor. The data are consistent with independent initiation of transcription on a genome-sized, negative-stranded template or on smaller templates. PMID- 6268832 TI - Cloning and expression of bacteriophage SP02 DNAZ polymerase gene L in Bacillus subtilis, using the Staphylococcus aureus plasmid pC194. AB - HindIII restriction endonuclease fragments of DNA from temperate Bacillus subtilis bacteriophage SP02 were cloned in B. subtilis by using the plasmid pC194. Three hybrid plasmids which permit growth of the mutant SP02 susL244 in suppressor-negative bacteria were isolated. SP02 gene L is thought to code for a DNA polymerase essential for autonomous replication of SP02 DNA. Extracts of bacteria carrying one of these hybrid plasmids, pC194-96, had 10- to 30-fold increased DNA polymerase activity. The plasmid-induced DNA polymerase activity differed from that of the known B. subtilis DNA polymerases in several respects. The results of the experiments support the idea that phage SP02 codes for a new DNA polymerase. PMID- 6268833 TI - Loss of functional large T-antigen and free viral genomes from cells transformed in vitro by polyoma virus after passage in vivo as tumor cells. AB - We have analyzed the state, arrangement, and expression of polyoma viral DNA sequences in a number of in vitro-transformed Fischer rat cells before and after growth in vivo as tumour cells. When the in vitro lines used to induce the tumors contained only a single insert of viral sequences and did not produce either a full-size 100,000-dalton (100K) large T-antigen or free viral genomes, no differences in the above-mentioned properties were observed. By contrast, in vitro cell lines containing multiple inserts of viral sequences, a functional 100K large T-antigen, and free viral genome induced tumor cells which displayed a reduced number of inserts of viral sequences and which did not produce either a functional 100K large T-antigen or free viral genomes. All of the in vitro lines and their tumor cell derivatives expressed the polyoma virus 55K middle and 22K small T-antigen species. Possible mechanisms for the selection in vivo against cells containing a functional 100K large T-antigen and consequently free viral genomes are discussed. PMID- 6268834 TI - Identification of a protein kinase activity in purified foot- and-mouth disease virus. AB - Purified preparations of foot-and-mouth disease virus types A, O, and C contain a protein kinase activity which can transfer the gamma phosphate of [32P]ATP to virion structural proteins VP2 and VP3 and exogenous acceptor proteins. Utilizing protamine sulfate as an acceptor, the kinase activity can be demonstrated in disrupted virus but not in intact virus. The enzyme is heat labile with optimal activity at pH 7 or greater. Serine residues of protamine sulfate were identified as the amino acid phosphorylated by the protein kinase. Treatment of purified virus with trypsin, which cleaves VP3, did not affect the protein kinase activity. The results indicate that the protein kinase activity found in FMDV is present in an internally located protein of viral or host origin. PMID- 6268836 TI - Identification of a packaged cellular mRNA in virions of rous sarcoma virus. AB - A novel messenger activity has been identified by in vitro translation of the 70S virion RNAs of a variety of avian leukosis and avian sarcoma viruses. When the 70S virion RNA complex was heat dissociated and the polyadenylated RNA was fractionated on neutral sucrose gradients, a polypeptide of 34,000 daltons (34K) was observed in the translation products of 18S polyadenylic acid-containing virion RNA. Aside from the p60(src)-related subgenomic messenger activities, this was the only prominent messenger activity that sedimented at <20S. It was determined that the 34K protein was not virally coded because (i) messenger activity for the 34K protein was not generated by mild alkaline hydrolysis of 35S genomic RNA, (ii) the 34K proteins synthesized in response to different virion RNAs had identical tryptic peptide maps, and (iii) the tryptic peptide map of the 34K protein coded for by virion RNA was identical to that of a major in vitro translation product of 34,000 daltons made from 18S uninfected chick cell polyadenylated RNA. The 18S RNA was shown to be contained within virion particles, rather than part of a cellular structure copurifying with virus preparations, by demonstrating the presence of 34K messenger activity in virion cores made from detergent-disrupted virus. This cellular mRNA, however, was not observed in the virion RNAs of Rous-associated virus types 0 and 2 avian leukosis viruses and therefore is not packaged by all avian retroviruses. Since no other cellular message has been detected by this assay, it seems likely that the 34K mRNA found in 70S virion RNA is the result of selective packaging of an abundant host cell mRNA by certain avian retroviruses. PMID- 6268835 TI - Glycoproteins of murine leukemia viruses. III. Glycosylation of env precursor glycoproteins. AB - We have compared the glycopeptides obtained after extensive pronase digestion of the env precursors (PrENV proteins) of ecotropic, xenotropic, and dual-tropic murine leukemia viruses. Two glycopeptide size classes, having molecular weights of approximately 2,200 and 1,500, were shown to be associated with the PrENV proteins of all murine leukemia viruses studied. Glycopeptides associated with the env precursors were totally susceptible to endo-beta-N-acetyglucosaminidase H. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of partial endo-beta-N-acetylglucosaminidase H digestion products of the env precursor of dual-tropic mink cell focus-forming virus (MCF 247) revealed the presence of seven bands, suggesting that six glycosylation sites were present on the precursor molecule. The MCF 247 PrENV protein had been previously shown to be accessible to lactoperoxidase-catalyzed radioiodination on the surface of infected cells. The cell surface PrENV molecules had the same electrophoretic mobility as pulse-labeled PrENV protein, and after endo-beta-N acetylglucosaminidase H treatment a similar shift in electrophoretic mobility was observed for the cell surface PrENV protein and the pulse-labeled precursors, a finding which indicated that the PrENV protein located on the cell surface also possessed only mannose-rich oligosaccharides. These results indicated that the env precursor glycoproteins of dual-tropic viruses had the unusual property of migrating to the cell surface without undergoing the normal oligosaccharide processing and proteolytic cleavage events that had been observed for ecotropic and xenotropic murine leukemia virus glycoproteins. PMID- 6268837 TI - Replication of simian virus 40 DNA in normal human fibroblasts and in fibroblasts from xeroderma pigmentosum. AB - Simian virus 40 infection of semipermissive human diploid fibroblasts (HF), at early passage in cell culture, was compared with that of permissive established monkey cell lines. Viral DNA can be readily detected at 24 to 48 h postinfection at 37 degrees C with a high multiplicity of infection, approaching 10% of that of monkey cells (TC7). The length of time necessary for replication of an average molecule of viral DNA was found to be indistinguishable in HF and TC7 cells. Strand elongation plus termination were assessed by following the accumulation of DNA I at 40 degrees C from replicative intermediates of tsA30 prelabeled at 33 degrees C, obviating isotope pool problems. Combined initiation and elongation of wild-type viral DNA was measured by density shift experiments involving a 5 bromodeoxyuridine chase of prelabeled [3H]thymidine-labeled viral DNA. Determination of accumulation of viral T and V antigens supports the conclusion that the most likely basis for the reduced virus yield in HF cells results from the inefficiency of an early stage in virus infection, before or during uncoating. Similar results were obtained in fibroblasts derived from patients with xeroderma pigmentosum, suggesting that enzymes of UV repair are not required in unirradiated simian virus 40 DNA synthesis. PMID- 6268838 TI - Molecular biology of rotaviruses. I. Characterization of basic growth parameters and pattern of macromolecular synthesis. AB - The United Kingdom tissue-adapted bovine rotavirus growing in African green monkey kidney (BSC-1) cells was selected as a model system with which to study the detailed molecular virology of rotavirus replication. Study of the kinetics of infectious virus production revealed a fairly rapid replication cycle, with maximum yield of virus after 10 to 12 h at 37 degrees C. Progeny genome synthesis was first detected during the virus latent period at 2 to 3 h postinfection. Study of the kinetics of viral polypeptide synthesis showed that virus rapidly inhibited cellular polypeptide synthesis such that by 4 h postinfection, only virus-induced polypeptides, 15 of which were detected, were being synthesized. No qualitative changes in the pattern of viral polypeptide synthesis were observed during infection, although, based on kinetic synthesis, three quantitative classes of polypeptides were defined. Pulse-chase analysis revealed three post translational changes in viral proteins, two of which were shown to be due to glycosylation. Tunicamycin inhibition studies were used to identify the putative non-glycosylated precursors of the two glycoproteins. Comparison of the infected cell polypeptides with those present in purified virions revealed that mot of the virus-induced proteins were incorporated into virions, with only VP9 being a truly nonstructural protein. Some localization of the various polypeptides within the purified virion was achieved by producing viral cores. PMID- 6268839 TI - Herpesvirus saimiri DNA in tumor cells--deleted sequences and sequence rearrangements. AB - Herpesvirus saimiri DNA in continuous lymphoblastoid cell lines obtained from viral induced tumors in marmosets has been analyzed by gel electrophoresis of restricted DNA. Southern transfer to nitrocellulose filters, and hybridization to 32P-labeled viral DNA or DNA fragments. The viral DNA fragments EcoRI-G, -H, -D, and -I, KpnI-A, and BamHI-D and -E were not detected in Southern transfers of DNA from the nonproducing 1670 cell line. For each restriction endonuclease, a new fragment appeared, consistent with a 13.0-megadalton deletion of viral DNA sequences. This deletion encompassed 35 to 48 +/- 0.6 megadaltons from the left end of the unique DNA region. A sequence arrangement map is presented for the major population of H. saimiri DNA sequences in the 1670 cell line. Although H. saimiri DNA in the nonproducing 70N2 cell line can be distinguished from viral DNA in the 1670 cell line by several criteria, the same sequences were found to be deleted in the major population of viral DNA molecules. Unlike 1670 and 70N2 cells, restricted DNA from the virus-producing cell lines 77/5 and 1926 contained all of the DNA fragments present in the parental virion DNA. DNA from 1670, 70N2, and 77/5 cells contained additional viral DNA fragments that did not comigrate with any virion DNA fragments. Most of these unexplained fragments were confined to or highly enriched in partially purified circular or linear DNA fractions. DNA from tumor cells taken directly from a tumor-bearing animal contained viral DNA indistinguishable from the parental virion DNA by the assay conditions used. These results indicate that viral DNA sequence rearrangements can occur upon cultivation of tumor cells in vitro and that excision of DNA sequences from the viral genome may play a role in establishing the nonproducing state of some tumor cell lines. PMID- 6268840 TI - Nucleotide sequences of the mRNA's encoding the vesicular stomatitis virus G and M proteins determined from cDNA clones containing the complete coding regions. AB - The complete nucleotide sequences of the vesicular stomatitis virus mRNA's encoding the glycoprotein (G) and the matrix protein (M) have been determined from cDNA clones that contain the complete coding sequences from each mRNA. The G protein mRNA is 1,665 nucleotides long, excluding polyadenylic acid, and encodes a protein of 511 amino acids including a signal peptide of 16 amino acids. G protein contains two large hydrophobic domains, one in the signal peptide and the other in the transmembrane segment near the COOH terminus. Two sites of glycosylation are predicted at amino acid residues 178 and 335. The close correspondence of the positions of these sites with the reported timing of the addition of the two oligosaccharides during synthesis of G suggests that glycosylation occurs as soon as the appropriate asparagine residues traverse the membrane of the rough endoplasmic reticulum. The mRNA encoding the vesicular stomatitis virus M protein is 831 nucleotides long, excluding polyadenylic acid, and encodes a protein of 229 amino acids. The predicted M protein sequence does not contain any long hydrophobic or nonpolar domains that might promote membrane association. The protein is rich in basic amino acids and contains a highly basic amino terminal domain. Details of construction of the nearly full-length cDNA clones are presented. PMID- 6268841 TI - Nucleotide sequences of the mRNA's encoding the vesicular stomatitis virus N and NS proteins. AB - The complete nucleotide sequences of the vesicular stomatitis virus (VSV) mRNA's encoding the N and NS proteins have been determined from the sequences of cDNA clones. The mRNA encoding the N protein is 1,326 nucleotides long, excluding polyadenylic acid. It contains an open reading frame for translation which extends from the 5'-proximal AUG codon to encode a protein of 422 amino acids. The N and mRNA is known to contain a major ribosome binding site at the 5' proximal AUG codon and two other minor ribosome binding sites. These secondary sites have been located unambiguously at the second and third AUG codons in the N mRNA sequence. Translational initiation at these sites, if it in fact occurs, would result in synthesis of two small proteins in a second reading frame. The VSV and mrna encoding the NS protein is 815 nucleotides long, excluding polyadenylic acid, and encodes a protein of 222 amino acids. The predicted molecular weight of the NS protein (25,110) is approximately one-half of that predicted from the mobility of NS protein on sodium dodecyl sulfate polyacrylamide gels. Deficiency of sodium dodecyl sulfate binding to a large negatively charged domain in the NS protein could explain this anomalous electrophoretic mobility. PMID- 6268842 TI - Partial purification and properties of an exonuclease inhibitor induced by bacteriophage Mu-1. AB - From an induced lysogen of bacteriophage Mu-1, we partially purified a substance of high molecular weight that blocks the action of several exonucleases on double stranded DNA. The presence of the inhibitor in cell-free extracts is dependent on induction of a Mu prophage. The Mu-related inhibitor acts by binding to double stranded DNA rather than by interacting with the DNase. The inhibitor protects linear duplex DNA of Mu, P22, and phi X174am3 from exonucleolytic degradation by recBC DNase and lambda exonuclease. Single-stranded DNA, however, is not protected by the inhibitor from degradation by either recBC DNase or exonuclease I. The inhibitor preparation contains a protein that binds to linear duplex DNA, but not to circular duplex DNA; ends are required for binding to occur. Single stranded DNA is not a substrate for the binding protein. These and other results suggest that the binding protein and the inhibitor are the same activity. PMID- 6268844 TI - Clonal analysis of the integration and expression of endogenous avian retroviral DNA acquired by exogenous viral infection. AB - Rous-associated virus-0 is one of several endogenous avian retroviruses that are transmitted vertically and that can be isolated from different inbred lines of chickens. These viruses, referred to here as induced-leukosis viruses bearing a subgroup E glycoprotein (ILV-E), are all closely related. Clonal populations of fibroblasts from line 15B and line 100 inbred chickens have been examined for the presence and expression of exogenously acquired ILV-E sequences. Restriction enzyme analysis of uniform populations of line 15B fibroblasts, prepared by cloning cells either before or after infection with ILV-E, indicates that viral sequences were inserted at multiple sites within the cell genome. Analysis of 49 clonal populations of line 100 fibroblasts containing between one and five copies of exogenous ILV-E sequences demonstrated that each clone was characterized by a unique set of viral DNA insertions within the cell genome. The expression of the exogenous ILV-E sequences within these fibroblast clones was examined by using reverse transcriptase activity as a measure of virus production. Some clones produced an amount of virus equivalent to that produced by an equal number of the uncloned ILV-E-infected parental fibroblasts. Other clones produced 5- to 10-fold less virus. Still other clones produced no detectable virus at all. Among nine clones derived from cells containing a single copy of the ILV-E provirus, the level of virus production differed more than 100-fold. DNA from these clones was analyzed with several different restriction endonucleases to characterize the location and arrangement of the ILV-E sequences. All nine clones consisted of cells that appeared to contain a complete provirus inserted (i) in a different site within the cellular DNA and (ii) in an orientation that was colinear with the viral genomic RNA. It was observed that several cleavage sites potentially affected by methylation were equally available for cleavage in all clones regardless of the level of viral production. PMID- 6268843 TI - Herpes simplex virus type 1 HindIII fragment L encodes spliced and complementary mRNA species. AB - We have used DNA bound to cellulose to isolate and translate in vitro herpes simplex virus type 1 (HSV-1) mRNA's encoded by HindIII fragment L (mapping between 0.592 and 0.647), and 8.450-base-pair (8.45-kb) portion of the long unique region of the viral genome. Readily detectable, late mRNA's 2.7 and 1.9 kb in size encoding 69,000- and 58,000-dalton polypeptides, respectively, were isolated. A very minor late mRNA family composed of two colinear forms, one 2.6 kb and one 2.8 kb, was isolated and found to encode only an 85,000-dalton polypeptide. A major early mRNA, 1.8 kb in size encoding a 64,000-dalton polypeptide, was also isolated. High-resolution mapping of these mRNA's by using S1 nuclease and exonuclease VII digestion of hybrids between them and 5' and 3' end-labeled DNA fragments from the region indicated that the major early mRNA contained no detectable splices, and about half of its 3' end was complementary to the 3' region of the very minor 2.6- to 2.8-kb mRNA's encoded on the opposite strand. These mRNA's also contained no detectable splices. The major late 2.7-kb mRNA was found to be a family made up of members with no detectable splices and members with variable-length (100 to 300 bases) segments spliced out very near (ca. 50 to 100 bases) the 5' end. PMID- 6268845 TI - Wild mouse ecotropic murine leukemia virus infection of inbred mice: dual-tropic virus expression precedes the onset of paralysis and lymphoma. AB - NFS/N mice inoculated at birth with an ecotropic murine leukemia virus (Cas-Br MuLV) obtained from wild mice developed hind limb paralysis beginning at 7 weeks of age and nonthymic lymphomas beginning at more than 20 weeks of age. Studies of 1- to 7-week-old Cas-Br-M MuLV-infected mice showed the following: (i) a marked increase in nonecotropic MuLV-related antigens on spleen cells but not thymocytes beginning at 2 weeks; (ii) the appearance of dual-tropic mink cell focus-forming (MCF) MuLV-related gp70 in spleen but not thymus or brain cells at 4 weeks; and (iii) the isolation of infectious MCF MuLV from spleen cells of 7-week-old mice. A role for MCF MuLV in Cas-Br-M MuLV-induced nonthymic lymphomas is indicated by these studies, and a role for recombinant MuLV in neurological disease is considered. PMID- 6268846 TI - Simian virus 40 maturation: chromatin modifications increase the accessibility of viral DNA to nuclease and RNA polymerase. AB - The accessibility of extracellular and nuclear simian virus 40 (SV40-M and SV40 I, respectively) virion chromatin DNAs to micrococcal nuclease, DNase I, BglI, EcoRI, and RNA polymerase was examined. Our results support the following conclusions: (i) the intranucleosomal DNA of SV40-I chromatin, similar to the precursor 75S chromatin complex, is resistant to enzymatic activity; and (ii) SV40-M virion chromatin is modified in a manner which increases the accessibility of viral DNA to enzymes, and the distinction between nucleosomal DNA and linker DNA is absent. Micrococcal nuclease digestion of SV40-I virion chromatin gave a typical nucleosomal DNA ladder pattern with a repeat unit of 205 base pairs of DNA. SV40-I chromatin was sensitive to cleavage with endonuclease BglI, but not with EcoRI. When SV40-I virion chromatin was used as a template, the rate of incorporation of ribonucleoside triphosphates into RNA was 5% of that obtained with naked form SV40 form I DNA. Micrococcal nuclease digestion of SV40-M virion chromatin resulted in submonomeric DNA fragments of approximately 55 base pairs, but no larger repeating unit of DNA was observed. SV40-M virion chromatin was sensitive to cleavage with either BglI or EcoRI and was approximately 20% more susceptible to digestion with DNase I than was SV40-I virion chromatin. The transcriptional efficiency of the extracellular virion chromatin was almost equivalent to that of naked SV40 form I DNA and was 16-fold higher than the rate observed with nuclear virion chromatin. The increased transcriptional activity was dependent upon the presence of nonhistone viral protein VP1 or VP2 or both. PMID- 6268847 TI - Molecular cloning of the avian myelocytomatosis virus genome and recovery of infectious virus by transfection of chicken cells. AB - The avian retrovirus myelocytomatosis virus 19 (MCV) possesses an interesting diversity of oncogenic potentials, but the virus has proven difficult to study because of its inability to replicate without the assistance of a helper virus. We have therefore isolated and amplified the genome of MCV by molecular cloning in a procaryotic vector. The topography of the cloned DNA was explored by the use of restriction endonucleases and radioactive complementary DNAs representing specific domains in avian retrovirus genomes. The cloned DNA appeared to be an authentic representation of the MCV genome: the size and genetic topography of the DNA were comparable to those of MCV, and transfection of the cloned DNA into chicken cells (in company with the DNA of a suitable helper virus) gave rise to virus with the genome and transforming potentials of MCV. The availability of cloned MCV DNA should facilitate a variety of genetic and biochemical manipulations directed at elucidating the mechanism of oncogenesis by MCV. PMID- 6268848 TI - Expression of murine leukemia viruses in the highly lymphomatous BXH-2 recombinant inbred mouse strain. AB - Among 12 recombinant inbred strains of mice derived from crossing two strains, C57BL/6J and C3H/HeJ, which have a low incidence of neoplastic disease, one strain (BXH-2) has been found to have a high incidence of lymphoma, of non-T-cell origin, at an early age. The BXH-2 strain carries the Fv-1b allele and spontaneously expresses a B-tropic murine leukemia virus beginning at as early as 10 days of gestation and continuing throughout their life. No significant differences in ecotropic virus titers were observed at any age tested (16 to 17 days of gestation through 7 months), whereas xenotropic virus was first detected in lymphoid tissues of 2-month-old mice and virus titers increased with age. Dual tropic virus(es), which induced cytopathic changes on mink lung cells, was isolated from BXH-2 lymphomatous tissues. Unlike AKR mink lung focus-forming virus (N-tropic recombinant), BXH-2 dual tropic virus is B tropic and induces cytopathic changes in mouse fibroblast cultures as well. The BXH-2 mouse provides a model system for studying the role of replication-competent viruses in spontaneously occurring leukemias of non-T-cell lineage and neurological disease. PMID- 6268850 TI - Rous sarcoma virus glycoproteins contain hybrid-type oligosaccharides. AB - Examination of [3H]mannose-labeled glycopeptides from Prague C Rous sarcoma virus gp85 with gel filtration and sequential glycosidase digestions demonstrated the presence of hybrid-type asparaginyl-oligosaccharides. The major hybrid species had an oligomannosyl core (Man5GlcNAc2-ASN) characteristic of neutral structures, plus "branch" sugars (NeuNAc-Gal-GlcNAc-) characteristic of complex, acidic structures. PMID- 6268849 TI - Transcription of vesicular stomatitis virus activated by pardaxin, a fish toxin that permeabilizes the virion membrane. AB - The toxic protein, Pardaxin, of the Red Sea flatfish Pardachirus marmoratus readily induced transcription of vesicular stomatitis virus by making the virion membrane permeable to nucleoside triphosphates in the absence of nonionic detergents. Virion transcription was activated over a wide range of Pardaxin concentrations, but at optimal concentrations, the rate of transcription exceeded that induced by Triton X-100. The inhibitory effect of M protein was manifested for both Pardaxin-induced and Triton-induced transcription at high concentrations of vesicular stomatitis virions; however, unlike the Triton-induced reaction, the inhibitory effect of M protein was not reversed by polyglutamic acid added to the Pardaxin-induced transcription reaction. We propose that activation of virion transcription by Pardaxin resembles more closely intracellular transcription initiated by virion penetration than does detergent-activated transcription of vesicular stomatitis virus. PMID- 6268851 TI - Epstein-Barr virus polypeptides: identification of early proteins and their synthesis and glycosylation. AB - We have identified at least six early polypeptides induced by Epstein-Barr virus in cells or under conditions which are nonpermissive for Epstein-Barr virus DNA replication ranging in molecular weight from 140,000 to 26,000. PMID- 6268852 TI - Structure of replicating herpes simplex virus DNA. AB - We have investigated the molecular anatomy of the herpes simplex virus replicative intermediates by cleavage with the restriction endonuclease BglII. We find that in populations of multiply infected cells, pulse-labeled replicating herpes simplex virus DNA contains at least two and probably all four sequence isomers. Also, it contains no detectable termini. In pulse-chase experiments, we show that endless replicative intermediates are the precursors to virion DNA and that maturation is a relatively slow process. The results are discussed in terms of their significance to possible models of herpes simplex virus DNA replication. PMID- 6268853 TI - Vestibular vertigo. A form of polyneuritis? AB - Vestibular vertigo traditionally has been considered to be of viral origin and some forms (acute vestibular neuronitis, acute labyrinthitis, acute vertigo) may be manifestations of a viral cranial polyneuritis. To test this hypothesis, otoneurologic signs and serum complement-fixation titers to herpes simplex and herpes zoster were determined in 16 patients with acute vertigo during their attack and several weeks later. One hundred unselected patients seen for nonotoneurologic problems served as control subjects. In addition to vestibular nerve abnormality, all patients with vertigo had some form of cranial nerve abnormality that cleared within four weeks of onset. These transient acute cranial nerve findings in patients with vestibular vertigo support the concept of inflammatory polyneuritis, and preliminary studies indicate that an anti inflammatory agent such as prednisone may be the preferred treatment. PMID- 6268855 TI - Silica and pulmonary lesions. PMID- 6268854 TI - In utero Epstein-Barr virus (infectious mononucleosis) infection. AB - A male infant infected in utero with Epstein-Barr virus (EBV) demonstrated a syndrome of multiple congenital anomalies (micrognathia, cryptorchidism, central cataracts), hypotonia, thrombocytopenia, persistent monocytosis, proteinuria, and multiple areas of metaphysitis at birth. Lymphocytes were Epstein-Barr nuclear antigen (EBNA) positive (18%) and persisted in culture for three months. He had antibody to early antigen (anti-EA), IgM-viral capsid (anti-VCA), and EBNA (anti EBNA) detectable at 22 days of age. All attempts to isolate infectious agents or to serologically identify other infectious causes for his syndrome were negative. PMID- 6268856 TI - The uncertain consequences of formaldehyde toxicity. PMID- 6268857 TI - Infectious mononucleosis and acute leukemia. PMID- 6268858 TI - Marijuana. Its health hazards and therapeutic potentials. Council on Scientific Affairs. PMID- 6268859 TI - [Effects of halothane anesthesia, epidural anesthesia and surgery on plasma beta endorphin levels in man (author's transl)]. PMID- 6268860 TI - [Effects of intrathecal injection of beta-endorphin on endocrine function in man (author's transl)]. PMID- 6268861 TI - [A case of acute promyelocytic leukemia successfully treated with allogeneic bone marrow transplantation (author's transl)]. PMID- 6268862 TI - [Electron microscopic studies of the red pulp of the spleen in various kinds of hemolytic anemia with special reference to the mechanism of hemolysis (author's transl)]. PMID- 6268864 TI - [Multidisciplinary treatment for undifferentiated small cell carcinoma of the lung (author's transl)]. PMID- 6268863 TI - [Extra-osseous accumulation of 99mTc-MDP in 2 cases of soft-tissue sarcoma (author's transl)]. PMID- 6268865 TI - [Usefulness of computed tomography in diagnosis of hepatocellular carcinoma with special reference to visualization of its capsule (author's transl)]. PMID- 6268866 TI - Burkitt's lymphoma cell line bearing surface IgA and negative for nuclear antigen of Epstein-Barr virus (EBNA). AB - A new continuous cell line, TL-1, was established in tissue culture from Burkitt's lymphoma arising at the ileocecal region. It has been maintained for the past two years. The cells were small and round, and grew in a suspension culture. Population doubling time was approximately 36 hours, The cells revealed the chromosomal abnormality i.e. translocation between 8 and 14 chromosomes, which was reported on some Burkitt's lymphomas. This line was negative for nuclear antigen of EB virus (EBNA) and bore surface IgA and not any receptors. Inoculums of 10(7) cells produced tumors in the athymic nude mice. The histological appearance of the tumor was consistent with the Burkitt's lymphoma. Ultrastructural findings showed nuclear blebs and clefts. As far as we know, this was the first cell line of Burkitt's lymphoma with t(8q-; 14q+) in Japan and perhaps the first lymphoma cell line with surface IgA. PMID- 6268867 TI - [Homologous transplantation of di-isopropanol nitrosamine induced pancreatic ductal adenocarcinoma in Syrian golden hamster (author's transl)]. PMID- 6268868 TI - [The recent status of vibration hazards among workers at the state forests in Hokkaido (author's transl)]. AB - In order to make clear the recent status of vibration hazards among workers belonging to the national forestry bureau in northern Hokkaido, a special health examination was carried out on 417 chain saw operators and 443 bush cutter operators. The results obtained are as follows: 1. Seven point seven percent of chain saw operators and 5.6% of bush cutter operators were diagnosed as suffering from vibration hazards. Distribution of the cases in chain saw operators was 50% in grade I, 31.2% in grade II and 18.8% in grade III, while in bush cutter operators it was 20% in grade I, 60.0% in grade II and 20.0% in grade III. 2. Six new patients were found in this special health examination. 3. Twenty-two of 76 authorized patients, who had been treated with periodical therapy and prohibited from the operation of vibratory tools until this special health examination, were diagnosed as having recovered their health because of the existance of no symptoms concerning vibration hazards. 4. Pains on pressure of the muscles were complained of at the upper arm, forearm, chest and at the back in 12.4% of chain saw and bush cutter operators. Deformities of the elbow, hand and finger joints were recognized in 12.6% of the workers, and ulnar nerve paralysis was recognized in 1.0% of them. 5. Occupational hearing loss and lumbago were diagnosed in 20.2% and 14.7% of the chain saw and bush cutter workers, respectively. PMID- 6268869 TI - [Studies of the propriety of the items adopted for the special health examination of vibration hazards at present (author's transl)]. AB - Skin temperature, vibratory sense, nail press test and pain sense are customarily used as the items in the special health examination for finding vibration hazards at present. These items are measured under the condition of room temperature at 20 to 23 degrees c and after 10-minute immersion in cold water at 5 degrees C or 10 degrees C. In this report, the propriety of these items was investigated on the basis of measurements in 274 healthy chain saw operators and 294 healthy bush cutter operators. The 10-minute immersion test in cold water at 10 degrees C was adopted in this experiment. The results obtained are as follows: Skin temperatures of the chain saw and bush cutter operators did not show any significant difference by age under the condition at the room temperature, but the recovery in the subjects in the twenties was faster than in the other. Skin temperatures at the 10th minute after the 10-minute immersion test in cold water at 10 degrees C showed very wide deviations among the subjects. Vibratory senses of the aged subjects markedly lowered in comparison with those of the younger subjects. Recovery of vibratory sense after the immersion in cold water showed a tendency which is faster than that of the skin temperature. Correlation between the skin temperature and the vibratory sense at the 10th minute after the immersion was statistically significant. Most of the subjects showed the recovery time within 2 sec with the nail press test under the condition of the room temperature and at the 10th minute after the immersion. Above 95% of subjects complained pain sense with one gram weight at the measurement under the all conditions except immediately after the 10-minute immersion test. From the above results, it should be considered that the value of these measurement may be dominated by the age of the subjects and that the immersion test in cold water to the tests of vibratory sense and pain sense may not have important role in the diagnosis of vibration hazards. PMID- 6268870 TI - [Studies on the toxicity of toluene (author's transl)]. AB - Toluene has been used widely as organic industrial solvent separately or together with other solvents. Many workers contact toluene resulting in acute and chronic poisonings. Problems studied include its acute and chronic epidemiology, toxicity on animals and human beings, dose-response relationships, fate in the living body (absorption, distribution, metabolism and excretion), maximum allowable concentration and biological monitoring limit value of this chemical. In this paper many recent reports of toxicity and metabolism of toluene are reviewed. PMID- 6268871 TI - [Adsorption and desorption of organic solvent vapours using silica gel (author's transl)]. AB - For a simple analysis of organic solvent vapours in working environmental air, we investigated the following method. First, join the adsorption tube (2 ml of 60- 80 mesh silica gel packed in a 5 mm phi x 18 cm glass tube) to hand vacuum pump and suck 200 ml of the sample air. After adsorption, join this adsorption tube to the sampling bottle under reduced pressure. Second, open the cock of the sampling bottle and heat only the adsorption tube in an oven for 3 min. In the operation mentioned above, organic solvent vapours desorbed from the silica gel transfer smoothly into the sampling bottle. After desorption, take 1 ml of air from the sampling bottle and determine the sample quantities with the gas chromatograph. Sample solvents used were as follows: n-hexane, cyclohexane, benzene, toluene, m xylene, styrene, 1.1.1-trichloroethane, dichloromethane, tetrachloroethylene, ethylacetate, acetone, methyl-ethylketone, methylisobutylketone, methanol, ethanol, n-propanol, and n-butanol. We obtained the following results. (1) 60--80 mesh silica gel is appropriate for this method. (2) Heating temperature to get 100% recovery varies with the type of organic solvent. m-Xylene and styrene require 250 degrees C, methylisobutylketone and n-butanol 200 degrees C, and the others 150 degrees C. (3) If the adsorption tube is preserved in a freezer at -20 degrees C, no decrease is observed for up to 7 days. At room temperatures, however, 1.1.1-trichloroethane, dichloromethane, tetrachloroethylene, n-hexane, and cyclohexane decreased by the amount 4-10% in the tube for each 24-hour period. These sample should be preserved at lower temperatures soon after absorbing on the silica gel. This method is simple and accurate, so valid for analysis of organic solvent vapours in the working environmental air. PMID- 6268872 TI - [On vibration hazards of chipping-hammer operators in an iron foundry. Part 1. Results of the first investigation (author's transl)]. PMID- 6268873 TI - [The effect of aging on the peripheral functions in farmers and chain saw operators. Part 2. Age-related changes in skin temperature and hyperemia time after pressing the nail (author's transl)]. AB - Vibration hazards which arise after exposure to mechanical vibration comprise various types of disorders, the most common of which are peripheral circulatory disturbances. It is now well recognized that aging effects all organ systems of the human body. The present study was therefore performed to assess the effects of aging on finger skin temperature and on hyperemia time after pressing the nail, both of which reflect peripheral circulatory functions. The subjects were 88 farmers and 86 chain saw operators ranging in age from 30 to 69 years, and 27 healthy persons aged 21 to 37 years as controls. Data were evaluated before and after cold water immersion tests in which the hand was immersed in 10 degrees C water for 10 minutes. The results obtained were as follows: 1) Before the test, skin temperature was negatively correlated with age, and hyperemia time was positively correlated with age in both farmers and chain saw operators but not in the case of the control subjects. 2)The skin temperature became lower, and hyperemia time grew longer with advancing age in both farmers and chain saw operators before and after the immersion tests. In comparison of the average skin temperature and hyperemia time between farmers and chain saw operators classified by age, the average skin temperature in chain saw operators was significantly lower than that in farmers, and the average hyperemia time in chain saw operators was significantly longer than that in farmers of every age group after the immersion test. The results suggest that we should take age-related changes into consideration to some degree when we evaluate the finger skin temperature and hyperemia time in diagnosing peripheral circulatory disturbances. PMID- 6268874 TI - [Vibration disorders in a factory producing concrete pipes and piles (author's transl)]. AB - The investigations were carried out to estimate the actual conditions of exposure and health of workers using impact wrenches and vibrating long iron trowels (Fig. 1) in a factory producing concrete pipes and piles, and the following results were obtained: 1) Vibration acceleration levels of the impact wrenches and the trowels were in excess of the guideline of up to 30 minutes per day proposed by ISO (1979) (Figs. 3 and 4). 2) Daily amounts of time during which workers were exposed to vibration by using tools were roughly calculated to be about 60 minutes per worker. 3) As the results of the special health examinations for 35 workers, 5 cases (14.3%) were diagnosed as vibration disease, 8 cases (22.9%) were suspected of this disease, and white fingers were found in 14.3% of the workers. It was suggested that the protection from vibration and the prevention of vibration disorders are necessary for all factories such that concrete pipes or piles are manufactured by similar processes. PMID- 6268875 TI - [Effects of immersion of hand in cold water (10 degrees C for 10 min) on the finger skin temperature of chain saw operators under different room temperatures (author's transl)]. PMID- 6268876 TI - [Clinical evaluation of scintigraphies with 99mTc-phytate and 67Ga-citrate as a screening test for hepatocellular carcinoma (author's transl)]. PMID- 6268877 TI - [Three cases of adenoid cystic carcinoma of the trachea (author's transl)]. PMID- 6268878 TI - Oncofetal antigen-I: distribution in human tumors. AB - Oncofetal antigen-I (OFA-I) is a human tumor-associated fetal antigen that cross reacts with fetal brain. The biological distribution of this antigen was studied in a variety of histologic types of human tumors and normal tissues. A total of 170 human tumors and 89 normal tissues obtained from biopsied and autopsied specimens were tested by immune adherence absorption assay. The antigen was most prevalent in malignant melanomas (82%); next in order of incidence were lung carcinomas (71%), sarcomas (61%), brain tumors (58%), and breast carcinomas (53%). However, OFA-I was found in only 15% of gastrointestinal tumors. The four hepatoma specimens tested were negative for OFA-I. OFA-I was also present in metastases and normal-appearing tissues of patients with OFA-I positive tumors but was not found in normal tissues from noncancer patients. These studies demonstrated that OFA-1 is widely distributed among human tumors. It appears to be more prevalent in tumors of ectodermal and mesodermal origin. PMID- 6268879 TI - Small cell carcinoma presenting as an extrapulmonary neoplasm: sites of origin and response to chemotherapy. AB - Eight (4%) of 203 consecutive prospectively staged and treated patients with small cell carcinoma (SCC) had no evidence of pulmonary or mediastinal tumor on chest roentgenogram or at fiberoptic bronchoscopy at the time of diagnosis. There were two distinct clinical presentations in these SCC patients with exclusively extrapulmonary tumors. Four had discrete localized extrapulmonary neoplasms, presumably originating in these sites. In the other 4 cases with either regional or widely metastatic disease, no obvious primary tumor could be documented in the lungs or elsewhere. One complete and two partial responses to chemotherapy (duration 6 to greater than 11 mo) occurred in 6 evaluable patients. Two remaining patients were inevaluable for response because they received adjuvant chemotherapy after irradiation or excision of the primary tumor and are free of disease at 15 and 28 months. Results document two clinicopathologic entities of extrapulmonary SCC, more firmly establish that it can be responsive to chemotherapy, and encourage systemic therapy as part of initial treatment planning. PMID- 6268880 TI - Feline uveal melanomas induced with feline sarcoma virus: potential model of the human counterpart. AB - Uveal melanomas were produced by injecting Gardner strain feline fibrosarcoma virus intraocularly into 10- to 15-day-old noninbred kittens. Tumors developed in about 90% of the cats' eyes receiving virus. Progressing tumors (62 eyes of 36 cats) began as small hyperpigmented lesions at the site of injection and grew to fill the anterior chamber by 3-5 months after infection. About 30% of cats with these tumors developed secondary tumors and died. Nonprogressive tumors characterized by flat, pigmented plaques on the iris at the site of injection developed in 25 eyes of 18 cats. These lesions did not enlarge except in proportion to the growth of the eye. Tumors were composed of pigmented spindle cells, pigmented epithelioid cells, and nonpigmented spindle cells. The cells could be grown for 5-8 passages in vitro. One culture assumed a transformed morphology and grew in noninbred athymic nu/nu mice. The lesions resembled human spindle cell melanomas. PMID- 6268881 TI - Goat lymphosarcoma from bovine leukemia virus. AB - A goat given inoculations of sheep lymphocytes from cultures that produced bovine leukemia virus (BLV) died 8 years later with lymphosarcoma. The tumors were located in various lymph nodes, the mesentery, omentum, body wall, and retrobulbar tissues. The BLV had been cultured from lymphocytes during the first year after the goat's infection, and persisting BLV antibodies could be demonstrated when the animal was 7.5 years old. BLV provirus was identified by molecular hybridization in the DNA of the goat tumors at the above five locations. The tumors were similar to those found in lymphosarcoma of the adult bovine type (BLV associated). Normal goat liver, normal calf thymus, and calf type lymphosarcoma (not BLV associated) served as negative controls. Our serologic, histologic, and molecular hybridization studies are evidence that the lymphosarcoma was induced BLV. PMID- 6268882 TI - A morphologic classification and incidence of spontaneous ovarian neoplasms in three strains of mice. AB - Ovarian tumors were reviewed and classified in 5,404 control inbred BALB/c, C57BL/6, and C3H mice. In descending order of frequency, the most common types in the C3H mice were the tubular mesothelioma (adenoma), thecoma, luteoma, granulosa cell tumor, and cystadenoma. In descending order the most common types in the BALB/c mice were the luteoma, tubular mesothelioma, granulosa cell tumor, thecoma, and cystadenoma. The tubular mesothelioma was the only ovarian tumor of significance in the C57BL/6 mice. Most of the ovarian tumors were rare before 1 year of age, but they increased with age after 1 year. PMID- 6268883 TI - Conjugated estrogens and breast cancer risk in women. AB - The relationship between conjugated estrogen(s) (CE) and breast cancer was investigated by the examination of the records of 345 women with newly diagnosed breast cancer and 611 healthy controls belonging to a prepaid health plan. Use of CE was associated with a 40% elevation in risk [relative risk (RR) = 1.4; 95% confidence interval-1.0-2.0]. The RR was 1.3 for menopausal women with intact ovaries and 1.5 for those with ovaries removed. There was statistically significant evidence of a dose-response relationship with the three measures of dose evaluated. RR's rose to about twofold for women with 10 or more CE prescriptions noted in their charts, for those with 5 years or more between their first and last prescription, and for those with a usual daily dose of 1.25 mg or more. The RR associated with having ever used CE and with long-term use was highest among those women with a family history of breast cancer. These data support the hypothesis that long-term use of CE is associated with increased breast cancer risk. PMID- 6268884 TI - Induction of endogenous mammary tumor virus expression during hormonal induction of mammary adenoacanthomas and carcinomas of BALB/c female mice. AB - Treatment of BALB/c female mice with pituitary isografts, under conditions that established mammary hyperplasia in an anovulatory condition, enhanced mammary tumor development with prior onset of dysplastic foci in lobular parenchyma. Tumor onset began at 8 months (mean onset time, 18 mo); the 25-month incidence was 100%. Adenoacanthomatous tumors appeared first. Adenocarcinomas appeared only after more than 14 months of continuous hormone stimulation. Dysplastic and neoplastic changes occurred while blood levels of the three major mammotropic hormones were physiologic. Murine mammary tumor virus (MuMTV) p28 was detected in all tumors tested, independent of time of tumor appearance or tumor type, although keratinizing cells in adenoacanthomatous tumors did not contribute to MuMTV antigen expression. MuMTV gp52 was detected in only a small fraction of cells in a few tumors. MuMTV RNA contents were above normal in all tumors tested. Neither MuMTV structural antigens nor RNA was induced in normal glands by the same hormone treatment that ultimately resulted in dysplasia and tumor formation and elevated levels of these viral markers in neoplasms. The MuMTV RNA in all hormone-induced tumors was readily distinguishable in base sequence from standard MuMTV RNA but indistinguishable from MuMTV RNA recovered from lactating mammary glands of BALB/c females carrying only endogenous MuMTV proviruses, suggesting that endogenous MuMTV RNA sequences were induced in hormone-induced neoplasms. RNA indistinguishable from MuMTV sequences present in hormone-induced primary tumors was also detected in multiple genomic equivalents in two independently derived hormone-induced premalignant alveolar hyperplasias. MuMTV p28 was detected, but gp52 was not. The same hormone stimulus that generated 100% tumors in normal gland greatly accelerated tumor development in premalignant hyperplasias but did not amplify MuMTV RNA or antigens in either hyperplasias or the tumors derived from them. B-type virions were not detected in these tissues, in either hypophyseal implant-stimulated or virgin hosts. Cell-free virions were not detected in culture. These data suggest that the replication of MuMTV induced in hormone-induced neoplasms is defective. Details of its expression suggest that if involved in events leading to tumors, its involvement is insufficient cause for those tumors. PMID- 6268885 TI - Determinants of susceptibility and resistance to feline leukemia virus infection. I. Role of macrophages. AB - The role of autochthonous peritoneal feline macrophages (M theta) in the age related resistance of cats to feline leukemia virus (FeLV) was investigated by a study of the functional properties and FeLV susceptibility of M theta from kittens and adult cats and the effect of hydrocortisone (HC) and silica on M theta-FeLV interactions. Although the phagocytic functions of isolated M theta from kittens and adults were equivalent, the mean FeLV susceptibility of M theta from kittens was five times that of M theta from adult cats, thus establishing a direct correlation between the age-related susceptibility of cats and M theta from cats to FeLV. M theta of viremic cats were found to be infected with FeLV in vivo; virus titers were slightly higher than those obtained after in vitro infection of M theta, M theta from cats that had experienced regressive FeLV infection were not significantly more resistant to FeLV infection in vitro than were M theta from naive adult specific-pathogen-free cats. HC, which has been shown to enhance the in vivo FeLV susceptibility of cats, also enhanced the permissiveness of M theta from cats to FeLV in vitro (600-fold for M theta from adult cats and 200-fold for M theta) from kittens. M theta permissiveness to FeLV was highly sensitive to HC and occurred in M theta infected in vivo or in vitro. In parallel with the effect of HC on the natural resistance of cats to FeLV, administration of silica before virus inoculation also markedly enhanced the FeLV susceptibility of adult cats. Silica was toxic for isolated M theta but not for lymphocytes in vitro, and silica produced monocytopenia and neutrophilia, delayed skin allograft rejection, and augmented feline oncovirus-associated cell membrane antigen antibody responses in vivo. These experiments indicate that M theta were linked to the natural resistance of cats to FeLV and that the temporary elimination of M theta functions (e.g., by silica) and/or the conversion of the M theta-FeLV relationship from a nonpermissive to a permissive state (e.g., by corticosteroids) resulted in failure of early virus containment, in persistent virus amplification in hemolymphatic tissues, and in subsequent FeLV-related proliferative or antiproliferative disease. PMID- 6268886 TI - Determinants of susceptibility and resistance to feline leukemia virus infection. II. Susceptibility of feline lymphocytes to productive feline leukemia virus infection. AB - The interplay between feline leukemia virus (FeLV) and feline lymphocytes (lc) infected in vitro or in vivo was investigated. Surface marker analysis and viral infectivity (VI) assays of lc populations were used to determine susceptibility of lc subsets to FeLV. The principal FeLV-replicating cell in the mesenteric lymph node of persistently infected, preleukemic cats was a nonadherent, complement receptor (CR)-bearing lc (B-cell). The lymph nodes of preleukemic cats also had increased numbers of uninfected T-cells [cells forming rosettes with guinea pig erythrocytes (GPE)] and cells with receptors for the Fc portion of 7S IgG (Fc gamma R cells) as compared with lymph nodes of age-matched specific pathogen-free (SPF) cats. The induction of productive infection of feline peripheral blood mononuclear leukocytes (PBL) in vitro depended on a 48-hour in vitro preincubation period before virus exposure. The equivalent susceptibility of whole and adherent cell-depleted PBL to productive infection and the failure of hydrocortisone to enhance viral infection were compatible with identification of the FeLV-replicating cell as an lc. Furthermore, lc from susceptible SPF kittens replicated 50 times as much FeLV as did lc from resistant adult SPF cats. The Ic productively infected with FeLV after in vitro exposure were more precisely identified with the use of Ficoll-Isopaque density gradient separations of rosetted and nonrosetted lc. Whole PBL, GPE rosette-positive PBL (T-cells), and CR-positive PBL (B-cells) were permissive to FeLV infection, and maximal VI was evident at 14 days after exposure. The substantial (1,325-fold) increment in VI found in the Fc gamma R-depleted PBL suggested a role for Fc gamma R cells in the containment of FeLV infection. Unstimulated mononuclear leukocytes from blood, spleen, lymph node, thymus, and marrow were susceptible to productive FeLV infection after in vitro exposure. The degree of spontaneous DNA synthesis in marrow, thymus, and spleen but not lymph node or PBL was inversely related to permissiveness to viral replication. Mitogen activation of lc was associated with decreased viral replication when either T-cell mitogens (concanavalin A, phytohemagglutinin, or pokeweed mitogen) or a B-cell mitogen (dextran sulfate) was used. Virus production by spleen cells and PBL was enhanced twofold to tenfold by prior lc stimulation by the B-cell mitogen, lipopolysaccharide, or protein A-bearing Staphylococcus aureus, a mitogen for feline T-cells with Fc gamma R. Both productively infected (preincubated) and nonproductively infected (freshly isolated) PBL transferred infectious FeLV to autochthonous peritoneal macrophages (M theta); most of the virus in PBL-peritoneal M theta cocultures was produced by adherent cells, irrespective of whether the adherent or nonadherent cell population was inoculated originally. PMID- 6268887 TI - Isolation of feline leukemia virus from a leopard cat cell line and search for retrovirus in wild felidae. AB - A strain of feline leukemia virus (FeLV), subgroup A, was isolated in early subpassage of a testicular fibroblast culture obtained from a captive Asian leopard cat. Neither FeLV nor RD-114 virus was recovered from cultured tissues of 15 other animals, representing eight species of wild Felidae. PMID- 6268888 TI - [Basic lipolysis stages and regulation pathways. Characteristics detectable in hypertension]. PMID- 6268889 TI - Rapid diagnosis of BK papovavirus infection. PMID- 6268890 TI - Prevalence of BK papovavirus antibody in patients with antinuclear antibodies. PMID- 6268891 TI - An electron microscopic study of cytomegalic inclusion body disease in the swine. PMID- 6268892 TI - [Nonuniform growth of the extremities in children]. PMID- 6268893 TI - [Vascular changes in developmental defects of the upper extremities in children, based on angiographic data]. PMID- 6268894 TI - [Indicators of the kinin system in various abdominal diseases]. PMID- 6268895 TI - [Potentials of functional scintigraphy in testicular diseases]. PMID- 6268896 TI - [Neurogenic tumors of the mediastinum]. PMID- 6268897 TI - [Renin-angiotensin-aldosterone system in diabetes mellitus]. PMID- 6268898 TI - Detection of cannabinoids in blood using EMIT. AB - A procedure for the detection of cannabinoids in blood (1 mL) using enzyme multiplied immunoassay technique (EMIT) is described. The sensitivity of the method, determined using 11-nor-delta 8-THC-9-carboxylic acid is better than 20 ng/mL. Estimates of precision and a study of storage effects show the method is applicable to blood samples normally encountered in toxicology casework. The method should be useful in screening and selecting blood samples for more specific confirmational procedures. PMID- 6268899 TI - Shock-induced changes in the sodium-potassium adenosine triphosphatase enzyme system in dog hearts. PMID- 6268900 TI - Can phosphorylation of histone H1 be responsible for chromatin condensation in mitosis? PMID- 6268901 TI - Fabry cardiomyopathy in the female confirmed by endomyocardial biopsy. AB - A 58-year-old woman with cardiac enlargement and heart failure was a member of a family with Fabry disease. In this patient, endomyocardial biopsy permitted microscopic examination of the myocardium which revealed cellular abnormalities characteristic of Fabry cardiomyopathy. It is suggested that unfavorable lyonization of the mutant-bearing X chromosome accounted for the expression of this disorder in specific organs of a female patient. PMID- 6268902 TI - Effects of thyroid hormones on cardiac hypertrophy and beta-adrenergic receptors during aging. AB - Administration of thyroxine daily at a dosage of 6.4 mu g/g body weight stimulates cardiac hypertrophy in both 9--13-month-old (mature, n = 34) and 22- 24-month-old (senescent, n = 45) Wistar rats. The increase due to thyroxine as well as the time course of the effect do not change with age, although ventricular wet weight to tibial length ratios are higher in senescent animals at 0, 3, and 7 days of treatment (senescent controls = 0.331; senescent hypertrophied = 0.395; mature controls = 0.295; mature hypertrophied = 0.336). Hypertrophy is maximal after 3 days. beta-Adrenergic receptor levels as measured by stereospecific binding of dihydroalprenolol in mature rats are increased about two-fold after 7 days of thyroxine treatment (mature controls = 35 +/- 3 fmol/mg protein, mature treated = 65 +/- 6 fmol/mg protein). Although both stimulated and control values do not differ significantly between mature and senescent groups (senescent controls = 45 +/- 4 fmol/mg protein, senescent treated = 56 +/- 9 fmol/mg protein), the effect of thyroxine on senescent hearts is not statistically significant. In addition, 3-day levels do not increase over 0-day controls at either age. No significant differences in either beta-adrenergic receptor concentrations or affinities between age groups are observed at 0, 3, and 7 days of treatment. However, senescent membrane preparations contain 33% more sialic acid (a rough plasma membrane marker) per unit of protein than mature preparations. Thus, the beta-adrenergic receptor density per unit of sialic acid may be reduced very slightly in the senescent hearts. PMID- 6268903 TI - [Angiotensin-converting enzyme in sarcoidosis: diagnostic and prognostic value (author's transl)]. AB - Between April 1976 and February 1980, serum levels of angiotensin-converting enzyme were determined in 61 cases of sarcoidosis at different stages of evolution. Cases were divided in three groups on the basis of social determinations done every 3-6 months. In the group with 46 active cases the increase in mean value of the enzyme is statistically significant compared to the control group; 30 of these (65.2%) had values higher than + 2DS. In the second group with 24 cases of non-progressive or inactive sarcoidosis the mean value was slightly higher than the normal mean value, without being statistically significant; 21 patients (87.5%) showed normal values: in the third group with 19 patients who had been treated with corticosteroids, mean value was equal to normal values; after 12 months treatment values were normal in 17 cases (89.5%). In the control group of 80 patients with a variety of pulmonary diseases other than sarcoidosis (pulmonary tuberculosis, pneumonia, pulmonary thromboembolism and primary lung cancer) only 9 cases presented values higher than the normal + 2SD (11.2% false positive). Serial determination of angiotensin-converting enzyme is a useful diagnostic parameter in sarcoidosis; especially in evaluating progression of the disease as well as the efficacy of corticosteroid treatment. PMID- 6268904 TI - Prostaglandins: gastrointestinal effects and peptic ulcer disease. PMID- 6268905 TI - Prostaglandins, vasopressin, and renal water reabsorption. PMID- 6268906 TI - [Melanotic progonoma with androgenic manifestations]. AB - The Melanotic Progonoma is not every common. It is frequent under a year of age however it has been in patients over 23 years old. It has several names. This tumor does not give metastasis, it is identified benign. It is located in several places like the anterior mediastinum, oropharynx, epididymis, particularly in the oral cavity. It is frequent in black people, less in the whites and exceptional in the indians. The kind of tumor has occasionally hormonal evident like acid vanil mandelico and androgens hypersecretion, with constant microscopic morphology. It cames from the neutral crest cells, then we think that the better name will be Neurocrestom Melanotic Infantile. PMID- 6268907 TI - [Acromelanosis and Wilms' tumor]. AB - Wilms tumour and Acromelanosis is a rare association. The authors describe two white cases, and they believe is an accidental a association. However, it's possible that Acromelanosis was a paraneoplastic sign if the future carry most similar cases. PMID- 6268909 TI - [Tick-borne encephalitis - a short review]. PMID- 6268908 TI - [Giant granulo-cellular Abrikosov's tumor]. AB - A case of Abrikossoff's granular-cell tumor is reported because of its unusually large dimensions (12.5 X 10.5 X 8.0 cm.), weight (700 g.) and supra-umbilical localization. Ample surgical excision of the tumor and reconstruction of the abdominal wall with silastic and skin graft were performed. Comments are made about the clinical, histopathological and histogenetic aspects of the neoplasia. PMID- 6268910 TI - Red cell ouabain binding sites, Na+K+-ATPase, and intracellular Na+ as individual characteristics. PMID- 6268912 TI - Peptide hormone degradation by a rat mast cell chymase-heparin complex. PMID- 6268911 TI - Effect of diltiazem, a calcium antagonist, on renin secretion from rat kidney slices. PMID- 6268913 TI - Determination of delta psi, delta pH and the proton electrochemical gradient in isolated cholinergic synaptic vesicles. PMID- 6268914 TI - Extracellular magnesium is not required for beta adrenergic drug-receptor interactions in intact human lymphocytes. PMID- 6268915 TI - Polycyclic aromatic hydrocarbon oxidation during prostaglandin biosynthesis. PMID- 6268916 TI - Behavioral comparisons of the stereoisomers of tetrahydrocannabinols. PMID- 6268917 TI - Evidence for opiate receptor binding in rat small intestine. PMID- 6268918 TI - Factor from rat small intestine potently affects opiate receptor binding. PMID- 6268919 TI - Solubilization of angiotensin II receptors in bovine adrenal cortex. PMID- 6268920 TI - Pre- and postsynaptic adrenergic activation by norepinephrine reuptake inhibitors in the field-stimulated rat vas deferens. PMID- 6268921 TI - Potentials evoked in the intermediolateral column by hypothalamic stimulation - suppression by delta 9-tetrahydrocannabinol. PMID- 6268922 TI - The role of calcium in the induction of ornithine decarboxylase in rat HTC cells. PMID- 6268924 TI - Calcium channel blocking agents. PMID- 6268923 TI - Effect of diabetes and insulin replacement on the lipid properties of hepatic smooth endoplasmic reticulum. AB - This study is a characterization of the lipid properties of the smooth and rough endoplasmic reticulum (SER, RER) of liver from streptozotocin-induced diabetic rats. A significant decrease in membrane microviscosity was observed in the SER but not the RER of diabetic rats when compared to that of normal controls. This decrease in SER membrane microviscosity correlated with a decrease in cholesterol/phospholipid ratio of these membranes that could be accounted for solely by a change in the membrane cholesterol content. Changes in phospholipid fatty acyl chain composition were also observed in the SER membranes but these changes were small when compared to the large change in cholesterol content observed. Insulin treatment for only one day did not significantly alter the microviscosity of the SER but after 2, 4 and 6 days of treatment both membrane microviscosity and membrane cholesterol content were restored to values similar to those for normal animals. No significant changes in the RER lipid composition were observed. It is well known that increases in glucose-6-Pase (G-6-Pase) activity of liver ER membranes are associated with diabetic onset. An increase in the specific activity of G-6-Pase was observed in both SER and RER membrane preparations, although the observed increase in the SER membrane is higher. The changes in the G-6-Pase activity of the SER membranes were correlated with the alterations in the microviscosity and lipid composition of these membranes. It is postulated that lipid properties of the SER membranes may contribute to the regulation of G-6-Pase activity in that membrane. PMID- 6268925 TI - [Several yellow fever cases in an endemic area in Ivory Coast: serological and epidemiological evidence (author's transl)]. AB - 1 - More than hundred febrile haemorrhagic jaundice cases with an unexpectedly high number of death happened in the north-west of the Ivory Coast between October 1977 and December 1977. It was the end of the rainy season and in this area, yellow fever is a dreadful eventuality. 2 - Epidemiological and serological survey was immediately carried out. Presence of numerous yellow fever potential vectors was well known and has been noticed in September 1977; there were some left in December 1977. Therefore no virus was isolated either in September or further. 3 - Haemagglutination-inhibition, complement-fixation and neutralization tests were performed with six flavivirus antigens, i.e. yellow fever, Wesselsbron, West Nile, Ntaya, Uganda S and Zika. 2 or 3 sera from 29 patients and 49 school children who have recent jaundice history, sometimes with haemorrhagic symptoms, were available. Single sera from 52 young rural workers and 402 inhabitants of surrounding villages were examined too. 4 - By the way of clinical, epidemiological, serological evidence, authors concluded 21 cases were certainly yellow fever. Evidence of 2 other cases was demonstrated by specific micropathological features. Furthermore, by serological results, 20 were probably yellow fever, 15 were inconclusive and 476 certainly not. 5 - Authors discussed some specific difficulties of yellow fever retrospective diagnosis in flavivirus endemic area. PMID- 6268926 TI - [Hemolytic anemia and consumption coagulopathy as a paraneoplastic syndrome in adenocarcinoma]. PMID- 6268927 TI - [Tissue selectivity and virulence indicators of 3 strains of Junin virus]. PMID- 6268928 TI - Internal potassium balance and the control of the plasma potassium concentration. AB - The plasma potassium concentration is determined both by external potassium balance and by the distribution of potassium between extracellular and intracellular fluid compartments, i.e., "internal potassium balance." Whenever external potassium balance is altered, the resultant change in the plasma potassium concentration is strongly influenced by concomitant alterations in internal potassium balance. Several factors alter internal potassium balance independently of changes in external balance. Acid-base disturbances produce shifts of potassium into or out of cells, but attempts to quantify these effects are not likely to be clinically useful. Hypertonicity produces a shift of potassium out of cells. Several hormones (insulin, aldosterone, catecholamines, glucagon, and growth hormone) may have roles in internal potassium balance. Digitalis and succinylcholine, by producing efflux of potassium from cells, may cause hyperkalemia. Potassium is released from skeletal muscle during exercise, causing an increase in the plasma potassium concentration. The periodic paralyses are associated with well-defined transient alterations in internal potassium balance. PMID- 6268930 TI - Glycerolipid acyltransferases from rat liver: 1-acylglycerophosphate acyltransferase, 1-acylglycerophosphorylcholine acyltransferase, and diacylglycerol acyltransferase. PMID- 6268929 TI - Hypoglycemia stimulates ACTH secretion through a direct effect on the basal hypothalamus. AB - The primary site of action of insulin hypoglycemia to induce ACTH secretion was investigated in rats with medial basal hypothalamic ablation (MBHA), medial basal hypothalamic deafferentation (MBHD), and chlorpromazine-morphine-pentobarbital (C M-P) treatment. Plasma corticosterone (B) concentration was used as an index of ACTH secretion. Hypoglycemia failed to provoke ACTH secretion in MBHA and C-M-P treated animals, while it stimulated ACTH secretion in MBHD animals to the same extent as in controls. The rise in plasma B induced by synthetic lysine vasopressin injection was not significantly different between MBHA and control animals, indicating pituitary ACTH reserve was not affected by the operation. Our data indicate that hypoglycemia stimulates ACTH secretion through a primary effect in the medial basal hypothalamus and not in the extrahypothalamic CNS or adenohyphophysis. PMID- 6268931 TI - 1,2-diacylglycerol: CDPcholine cholinephosphotransferase. PMID- 6268932 TI - Phosphatidylglycerophosphate synthase from Escherichia coli. PMID- 6268933 TI - Phosphatidylserine synthase from Escherichia coli. PMID- 6268934 TI - CTP: phosphocholine cytidylyltransferase from rat liver. PMID- 6268935 TI - Phospholipase C from Clostridium perfringens. PMID- 6268936 TI - Cosmid cloning and transposon mutagenesis in Salmonella typhimurium using phage lambda vehicles. AB - We have constructed a strain of Salmonella typhimurium which contains the malB region from Escherichia coli and carries the bacteriophage lambda receptor protein in its outer membrane. Phage lambda adsorbs to this strain but cannot grow, thus providing a very useful system for transposon mutagenesis of S. typhimurium using lambda vehicles carrying transposons. This system can also be used for cosmid cloning. PMID- 6268937 TI - The sequence of IS4. AB - IS-elements are devoid of easily recognizable transacting functions and exert their visible effects in the position cis only (recent reviews Calos and Miller 1980; Starlinger 1980). It has been a matter of debate, whether these elements encode functions for their own transposition. In the case of the E. coli IS elements this could not easily be determined by genetic methods, because most of these elements are present in several copies (Saedler and Heiss 1973; Deonier et al. 1979). In the case of the IS-elements flanking transposons, evidence has recently been brought forward that these carry the transposition specificity (Rothstein et al. 1980; Kleckner 1980; Grindley 1981). IS4 is present in one copy only in several E. coli K12 strains and should, therefore, be suitable for genetic and physiological studies (Chadwell et al. 1979). It has been cloned from several sites on the E. coli chromosome in pBR322 (Klaer and Starlinger 1980). Here we report the DNA sequence of IS4 which contains an open reading frame for 442 amino acids, and of the junctions of this element with surrounding DNA at three different sites in the E. coli chromosome. PMID- 6268938 TI - The structure of R1drd19: a revised physical map of the plasmid. AB - We have analyzed derivatives of the plasmid R1drd19 carrying the transposon Tn10 by electron microscopy following denaturation and renaturation of the molecules, and by digestion with various restriction enzymes, gel electrophoresis and Southern blotting. We show: 1) that the published restriction map of R1drd19 is inconsistent with our results. We present a modified map which is consistent with our data. 2) that R1drd19 carries a single resident copy of the element IS10 which is normally associated with Tn10 as an inverted repeat, and 3) that R1drd19 carries three copies of the insertion element IS1 in the resistance determinant region. PMID- 6268939 TI - Mapping of IS1 elements flanking the argF gene region on the Escherichia coli K 12 chromosome. AB - Two directly-repeated IS1 elements have been mapped on the Escherichia coli K-12 chromosome at positions 23.2 kb and 34.5 kb counterclockwise of the IS3 element alpha3beta3 by using F-prime plasmids (including the F lac- proAB+ plasmid F128) that carry different portions of the bacterial chromosome in the purE to proA region. Mapping was accomplished in part by construction of EcoRI, BamHI, and BglII restriction enzyme cleavage maps. Electron microscope heteroduplex and hybridization studies indicate that the chromosomal region flanked by these IS1 elements is completely homologous to the IS1-argF-IS1 region (Tn2901) on the P1argF5 transducing phage (York and Stodolsky, 1981), which suggests that the argF gene region in the usual E. coli K-12 strains has a transposon-like structure. PMID- 6268941 TI - Isolation of DNA fragments containing replicating growing forks from both E. coli and B. subtilis. AB - By the use of a restriction enzyme digestion of gently lysed E. coli or B. subtilis cells, it is possible to isolate a minute fraction of the total DNA that has an unusually high sedimentation coefficient. Upon inspection of this DNA in the electron microscope, branched DNA fragments are observed. Single branched DNA fragments were analyzed by restriction enzyme and partial denaturation mapping techniques. The fragments appear to have the properties of growing forks excised from in vivo replicating intermediates. In B. subtilis, the minute fraction of DNA was also investigated by transformation assays and found to be greatly enriched for a marker near the origin and slightly enriched for a terminus marker. PMID- 6268940 TI - Characterization of P1argF derivatives from Escherichia coli K12 transduction. I. IS1 elements flank the argF gene segment. AB - Specialized transducing derivatives of the temperate bacteriophage P1 (P1std) are selected by transduction into recipients with deletions in the corresponding genes (Stodolsky 1973). When Escherichia coli K12 strains are used as donors in such transduction experiments, P1argF derivatives can be selected. The argF gene is unique to these strains (Glansdorff et al. 1967). Under these experimental conditions P1argF are formed with frequencies 10,000 times greater than other P1std. The majority of the P1argF derivatives that have been analyzed are indistinguishable by cleavage analyses. One such derivative, P1argF5 has been characterized in detail. Heteroduplex analysis against P1, P7, and P1CmO identified an 11 kb insertion of DNA precisely at the naturally occurring IS1 locus of P1. Cleavage analysis with EcoRI, BamHI and PstI confirmed this finding. To further define the argF insertion, a P1Cm13argF derivative was constructed having the IS1 sequences of Cm13 and argF in opposite orientation. Intrastrand annealing of P1Cm13argF5 DNA established that the argF segment is flanked by directly repeated IS1 sequences. The IS1-argF-IS1 segment is designated Tn2901. The assignment of the map position of the argF gene within the 11 kb insert of P1argF5 is discussed. The evolutionary significance of this finding and a model for P1argF formation is also presented. PMID- 6268942 TI - Molecular cloning in streptococci: physical mapping of the vehicle plasmid pSM10 and demonstration of intergroup DNA transfer. AB - The streptococcal resistance plasmid pSM10 (8.3 kb), a deletion derivative of pSM10419 (22.9 kb) determining constitutive erythromycin and lincomycin resistance, was physically mapped with the restriction endonucleases AvaI, AvaII, EcoRI, HpaI, KpnI, PvuII (one site each), HindIII, HaeII (three sites each), HincII (four sites), and HhaI (five sites). Using the cryptic plasmid pVA318 as cloning vehicle, the largest HindIII fragment of pSM10 (3.3 kb) was shown to contain the erythromycin/lincomycin resistance gene(s) of the plasmid. The AvaII site of pSM10 proved to be suitable as a site for cloning AvaII-generated chromosomal DNA fragments from a group C streptococcal strain in the Challis strain of Streptococcus sanguis (group) H). A detailed physical map of the chimeric plasmid pSM10221 (12.8 kb), a fusion product of pSM10 and the staphylococcal chloramphenicol resistance plasmid pC221 (4.5 kb), is also presented. The plasmid chimera has properties making it potentially useful in development of a doubly selective streptococcal cloning vehicle by searching for insertional inactivation. PMID- 6268943 TI - Induction of transformed phenotypes in sheep fibroblasts by culture fluids from cells persistently infected with bovine leukemia virus. AB - FLK cells are fetal lamb kidney cells persistently infected with bovine leukemia virus (BLV). 3178 cells, originating from calf-form bovine lymphosarcoma, also showed persistent production of BLV and alteration of cell morphology, after treatment with 5'-iodo-2'-deoxyuridine. In the present paper, the first in vitro transformation of sheep fibroblasts by inoculation with BLV materials from these two cell lines is described. In a few passages after inoculation with these viral materials, morphological alteration occurred. The morphologically altered cells were grown as stable cultures and showed such transformed phenotypes as growth in soft agar medium, increased uptake of 2-deoxy-D-glucose and tumorigenicity in athymic nude mice. This result, together with our previous observation of simultaneous induction of BLV expression and morphological alteration of 3178 cells, suggests the presence of some transforming capacity in these BLV materials similar to that in, for example, murine or avian acute leukemia viruses. The possible acquisition of such capacity during the prolonged passage is discussed. PMID- 6268944 TI - Inhibitory effect of 1-beta-D-arabinofuranosylthymine on synthesis of Epstein Barr virus. AB - The effect of 1-beta-D-arabinofuranosylthymine (ara-T) on cell growth and synthesis of Epstein-Barr virus (EBV) in human lymphoblastoid cell lines was determined. The growth of P3HR-1 cells was not inhibited by 1 microgram of the drug per ml; however, infectious virus production was strongly inhibited and was accompanied by decreased expression of early antigen (EA) and viral capsid antigen (VCA). The ability of 12-O-tetradecanoylphorbol-13-acetate or n-butyric acid to induce synthesis of VCA, but not EA, in P3HR-1 cells was inhibited by ara T. Similarly, VCA synthesis but not EA synthesis was inhibited by ara-T in Jijoye cells superinfected with the P3HR-1 strain of EBV. The results suggest that ara-T has a specific inhibitory action against EBV replication. PMID- 6268945 TI - Structural proteins of poliovirus type 2 isolates. AB - Seventeen strains of type 2 poliovirus isolated from vaccines and vaccine contacts in Japan were analyzed for viral structural proteins by sodium dodecyl sulfate polyacrylamide gel electrophoresis. An alteration in electrophoretic mobility of VP1 was observed in most of the strains from paralytic patients and healthy vaccinees. The alteration in VP1 was observed at a high frequency among many strains, but no significant relation between the mobility change of VP1 and antigenic marker or rct/40 marker was observed. No alteration in mobility of other structural proteins was observed among the strains examined except for one with altered VP3. The results suggested that VP1 of Sabin type 2 strain was easily changeable during replication in human intestines. PMID- 6268946 TI - Electrochemical modification of vesicular stomatitis virus glycoprotein by host cell transformation. AB - Electrochemical properties of the glycoprotein of vesicular stomatitis virus (VSV) grown in Rous sarcoma virus (RSV)-transformed cells was compared with that of its counterpart grown in nontransformed cells. In DEAE-Sephadex column chromatography, the glycoproteins of VSV derived from transformed cells appeared more heterogeneous and had a tendency to elute with higher concentrations of NaCl than those from nontransformed cells. In isoelectric focussing, the glycoproteins of VSVs derived from transformed and nontransformed cells appeared as multiple components differing in the isoelectric point, and the glycoproteins from virus from transformed cells had isoelectric points that were more acidic than their counterparts from nontransformed cells. These results show that the glycoprotein of VSV consists of populations of molecules differing in charge and their isoelectric points were shifted to the acidic side by host cell transformation. PMID- 6268947 TI - Glycoprotein of hepatitis B surface antigen (HBsAg) produced by PLC/PRF/5 hepatoma cells. PMID- 6268948 TI - Restriction endonuclease analysis of the genomes of virulent and avirulent Marek's disease viruses. AB - The DNAs from virulent strain BC-1 and avirulent strains C2(A) of Marek's disease virus (MDV) were compared by electrophoresis on 0.5% agarose gels of the products obtained with the restriction endonucleases Bam H1, Sal 1, and Sma 1. The patterns of the fragments of the DNAs from these two strains were very similar, but showed some significant differences in the number and mobility of the DNA bands. The DNA fragments obtained with the restriction endonucleases, and especially Sma 1, were mostly present in equal molar ratios, but a few of those obtained with Bam H1 and Sal 1 were present in submolar amounts. In addition, several fragments obtained with Bam H1 and Sal 1 were present in greater than molar quantities, suggesting the presence of reiterated sequences in MDV DNA. The terminal fragments of MDV DNA were identified by their sensitivity to lambda 5' exonuclease. The terminal fragments obtained with Bam H1 A and Sal 1B showed heterogeneous electrophoretic mobility and contained sequences with high content of guanosine and cytosine, suggesting the presence of reiterated sequences at the end of the MDV DNA molecule. PMID- 6268950 TI - A proposed mechanism of action of the inotropic agent digitalis. PMID- 6268949 TI - [Ultrastructural characteristics of the rotavirus detected in swine with gastroenteritis]. PMID- 6268951 TI - Smooth muscle phenotypic modulation: role in atherogenesis. AB - Observations in vivo and in vitro demonstrate: 1) smooth muscle cells are capable of more than one function and can alter their phenotype/state accordingly (modulation); 2) in the majority of cases before a smooth muscle can divide it must modulate from a contractile to a synthetic phenotype; 3) modulation is reversible; 4) however, if synthetic state smooth muscle which has been stimulated to divide achieves approximately nine cell doublings before being inhibited by confluence it appears unable to return to the contractile state; 5) smooth muscle cells in the synthetic state respond almost immediately to serum mitogens and have an altered ability to metabolize low density lipoprotein compared with those in the contractile state 6) diffuse intimal thickenings and intimal cushions at branch points form from the media apparently as a result of adaptation of the vessel wall to growth and development and are sites of predilection for the formation of atherosclerotic plaques. The "smooth muscle metabolic reactivity" hypothesis of atherogenesis suggests that due to the large number of smooth muscle cell doublings which occur in the formation of diffuse intimal thickenings and intimal cushions at branch points a number of these cells are permanently in the synthetic state. This confers upon these cells a selective proliferative advantage and an altered ability to metabolize lipoproteins - both essential ingredients in atherogenesis. PMID- 6268953 TI - Antimicrobial therapy in whooping cough. AB - We compared the ability of erythromycin and co-trimoxazole in clearing Bordetella pertussis from the nasopharynx of 22 children admitted to hospital with whooping cough. Both agents appeared effective. Nevertheless, 10 of the 22 patients gave positive cultures four or more days after antimicrobial administration was begun. PMID- 6268952 TI - Cardiac nuclear medicine, part I: the methods. AB - With the rapid improvement in instrumentation and radiopharmaceuticals, cardiovascular nuclear medicine has undergone dramatic growth. Radiotracer techniques for the estimation of myocardial blood flow, metabolism and cardiac hemodynamics have been accepted into routine clinical practice. These techniques are also providing sensitive tools to help us elucidate cardiac physiology and pathophysiology. Three commonly used examinations are: technetium-99m pyrophosphate imaging for the detection of irreversibly damaged myocardium; thallium-201 imaging for the evaluation of myocardial perfusion and integrity; and cardiac wall motion studies with technetium-99m labeled red blood cells for the assessment of ventricular contraction. This is the first part of a three-part series on cardiac nuclear medicine. Part II will focus on diagnosis of coronary artery disease, and part III will focus on myocardial infarction and other cardiac diseases. PMID- 6268954 TI - Ketoconazole (Nizoral). A new antifungal agent. PMID- 6268955 TI - Protectivity of herpes simplex virus antigens: studies in mice on the adjuvant effect of PICLC and on the dependence of protection on T cell competence. AB - The efficacy of a herpes simplex virus type 1 (HSV-1) envelope antigen (EAG) preparation against HSV infection was studied in T cell competent and T cell deficient mice. Immuno-competent mice were successfully protected against herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2) infection when immunized 2 weeks prior to this infection with a heat-inactivated whole virus preparation or a HSV 1 envelope antigen (HSV-1 EAG) preparation. Since HSV-1 EAG was considerably less effective than the whole virus preparation, a poly.riboinosinic poly.ribocytidylic acid complex with poly-L-lysine and carboxymethylcellulose (PICLC) was used as adjuvant. Immunization with HSV-1 EAG plus PICLC resulted in a pronounced increase of this protection rate as compared with that obtained after immunization solely with HSV-1 EAG. PICLC alone, however, offered no protection when given 2 weeks before challenge. In T cell deficient nu/nu mice no protection was achieved with HSV-1 EAG while their T cell competent, heterozygous littermates were protected. From these results it may be concluded that T cell competence is a prerequisite for establishing a protective immunity against HSV infection after immunization with HSV-1 EAG. PMID- 6268956 TI - A modified absorption-reduction method to detect virus-specific hemagglutination inhibiting and neutralizing IgM antibodies. AB - IgG antibodies are preferentially absorbed by protein A-coupled sepharose beads while most of the IgM and IgA antibodies remain in solution. Even relatively low amounts of virus-specific IgM antibodies can then be detected unequivocally by a decrease of the antibody titer following the treatment with reducing agents. Ethandithiol proved superior to 2-mercaptoethanol in combination with neutralization assays. PMID- 6268957 TI - Use of the enzyme-linked immunosorbent assay (ELISA) for the estimation of serum antibodies in an influenza virus vaccine study. AB - The value of the enzyme-linked immunosorbent assay (ELISA) for determining the serum antibody responses of volunteers following immunisation with various inactivated influenza virus vaccines was assessed, and the incidence of seroconversions, as measured by both haemagglutination-inhibition (HI) and ELISA response of the volunteers determined. ELISA was found to be more sensitive than the HI test in detecting serum antibodies, but was also less specific under the conditions used. With regard to efficacy, the whole virus vaccine proved to be more effective in inducing serum antibody in an unprimed population than either tween-ether split or subunit adsorbed vaccines, but the reverse situation held when the population was primed with respect to the antigen concerned. PMID- 6268959 TI - [Reproductive characteristics of the tick-borne encephalitis and Powassan viruses in Dermacentor silvarum imago explants removed from the nymphal cuticle]. PMID- 6268960 TI - [Nomenclature for strains of poliovirus]. PMID- 6268958 TI - The influence of different modes of immunization on the experimental genital herpes simplex virus infection of mice. AB - Previous investigations, which simulated the usual sequence of the human Herpes simplex virus (HSV) infections, had shown that the oral infection of mice with HSV-1 caused only weak protection from genital infection with HSV-2, although the course of infection was attenuated and lethality diminished. This heterologous, heterotopic model was compared with a homologous, heterotopic and a heterologous, homotopic model. The results did not differ very much, although the homologous immunization protected best from lethal outcome, the homotopic immunization best from local infection. Three different preparations of a killed vaccine from purified HSV-1 virion had little effect on the course of the local infection, although protection from lethal outcome was as good as with live virus. In contrast, a crude UV-inactivated vaccine protected nearly completely from local infection. Latent infection in the lumbosacral ganglia was significantly inhibited by immunization with live virus, but only slightly prevented by killed vaccine. The prevalence of latent infection correlated with the extent of vaginal infection. The results show that neither the viral type nor the inoculation site used for immunization with live virus are very critical. Moreover, they allow the conclusion that generalized type-dependent immune factors seem to be engaged in protection against lethal disease; these may be circulating humoral antibodies. On the other hand, locally induced immune factors (probably cellular) are apparently of prime importance for the protection from acute local and latent ganglionic infection. PMID- 6268962 TI - Insulin release: reconciliation of the receptor and metabolic hypotheses. Nutrient receptors in islet cells. AB - Nutrients which stimulate insulin secretion are currently thought to initiate the series of cellular events eventually leading to insulin release either by interacting with a stereospecific receptor system (the regulatory site hypothesis) or by acting as a fuel (the substrate site hypothesis) in the pancreatic B-cell. The latter hypothesis is supported by a number of observations indicating that the capacity of nutrients to stimulate insulin release is indeed highly dependent on their capacity to increase catabolic fluxes in isolated pancreatic islets. However, these observations do not rule out the existence of nutrient receptors in islet cells. For instance, a nonmetabolized analog of L leucine stimulates insulin release by causing allosteric activation of glutamate dehydrogenase, which should be considered, therefore, as a receptor for certain amino acids. Likewise, the increase in glycolytic flux, which is associated with the process of glucose-stimulated insulin release, is attributable not solely to a mass action phenomenon but also to the activation of phosphofructokinase by fructose 2.6-bisphosphate. The biosynthesis of this activator may involve a glucose receptor system. The fact that certain nutrient secretagogues (e.g. D glucose and L-leucine) act in the B-cell both as substrates and enzyme activators permits reconciliation of the substrate site and regulatory site hypotheses for insulin release. PMID- 6268963 TI - Interaction of vasoactive intestinal peptide with a cell line (HeLa) derived from human carcinoma of the cervix: binding to specific sites and stimulation of adenylate cyclase. AB - The binding of vasoactive intestinal peptide (VIP) and its effect on cyclic AMP production were assessed in HeLa cells. The binding of [125I]VIP is a moderately rapid process, reversible, saturable, specific and dependent on temperature. Virtually no inactivation of the peptide is observed after 2 h of exposure to the cells. At 15 degrees C, the binding data obtained at steady state are compatible with the existence of two classes of binding sites: a first class with a Kd of 2.4 nM and low binding capacity (1.5 X 10(5) sites/cell) and a second class with a Kd of 100 nM and a high binding capacity (4.9 X 10(6) sites/cell). Secretin is eight times less potent than VIP in competing with 125I VIP but glucagon, insulin and somatostatin are inactive. VIP-induced stimulation of cyclic AMP production depends on time and temperature and is potentiated by a phosphodiesterase inhibitor. A concentration of VIP as low as 10(-10) M is able to stimulate adenylate cyclase. Half-maximal stimulation is observed at 10(-9) M and maximal stimulation (4 times above basal levels) at 10(-8) M VIP. Secretin is an agonist of VIP but exhibits a 1000 times lower potency with respect to adenylate cyclase activation. Glucagon, insulin and somatostatin do not show any effect. The presence of high-affinity binding sites and high sensitivity and specificity of adenylate cyclase for VIP in HeLa cells provide a good model to study the role of this peptide on cell proliferation and differentiation. PMID- 6268964 TI - [Col E1 DNA transcription in Escherichia coli RNA-polymerase system in vitro]. AB - The ColEI plasmid DNA transcription in E. coli RNA-polymerase system in vitro was studied. Three RNA types: of 110-140 residues long, 1700 residues long and of the length similar to that of DNA-template were synthesized in the reaction, containing 10 mM MgCl2, 50 mM KCl and 15% glycerol. The transcription was shown to be asymmetric, the DNA H-chain being transcribed. The ColEI DNA region transcribed in vitro was located by the blotting techniques. This region comprised most of the ColEI genome except the colicin EI gene. The addition of mitomycin C to the reaction mixture caused only a little stimulation of colicin EI gene transcription. Four fragments of HaeIII digest of ColEI DNA were shown to have affinity to RNA-polymerase in the absence of NTPs and two fragments to have it in the presence of 3 NTPs (in the RNA initiation conditions). These two fragments seem to contain two strong promoters. One of them is in the HaeIIIA fragment, where the colicin EI gene origin is situated, and another one is the HaeIIIB fragment (in the immunity region). PMID- 6268965 TI - [Structural organization of rat ceruloplasmin gene]. AB - Distribution of ceruloplasmin-coding sequences among fragments of rat nuclear DNA obtained after complete cleavage with seven restriction endonucleases was studied using highly specific complementary DNA probes. Three different procedures were used for the synthesis of cDNAs, whose relative advantages and disadvantages are discussed in this work. The number of restriction fragments carrying ceruloplasmin gene sequences varied from two to five depending on the enzyme used. The total molecular weight of these fragments was several times higher than the minimal length of ceruloplasmin structural gene deduced from the molecular size of mRNA. The restriction endonuclease cleavage of the partial double stranded transcript of ceruloplasmin mRNA coding for about 60% of its length from the 3'-end has shown that distribution of restriction endonuclease cleavage sites on the dsDNA differs in the position of cleavage sites on the ceruloplasmin gene in cellular DNA. Hybridization of cDNA with total cellular DNA allows to determine 1.3-1.4 copies of ceruloplasmin gene in the rat haploid genome. Proceeding from the data obtained it may be stated that the rat ceruloplasmin gene is constructed of several structural gene segments cut by introns. PMID- 6268966 TI - [Restriction mapping of T4 bacteriophage late gene region which contains the origins of DNA replication]. AB - DNAs of lambda T4 recombinants 596-27 (genes 50-5), 596-30 (genes 50-8), 596-29 (genes 50-12), 591-16 (genes 6-8), 591-1 (genes 9-12), 596-13 (genes 13-16), 596 17 (genes 18-20) and 596-11 (genes 25-29) were mapped with the use of EcoRI, HindIII, SmaI, SalI and BamHI restriction enzymes. T4 dcDNA was digested with HindIII restriction endonuclease and resulting fragments were cloned into HindIII lambda vector 761. The recombinants 761-7, 761-17, 761-19, 761-24, 761-44, 761 50, 761-55 contained the region of genes 25-48 and 761-42, 761-26 and 761-16 contained a single HindIII-fragment with genes 6-12 in both orientations. Data obtained with the DNA of the latter recombinants allowed to show the correctness of the map established earlier which did not contain a full set of overlapping sequences. As a result of the experiments reported, the position of EcoRI and HindIII recognition sites in the region of genes 50-20 and 25-48 was determined and in the region of genes 25-48 BglII and XhoI restriction sites were mapped. The location of a single BamHI restriction site in the region of gene 8 was also established. PMID- 6268967 TI - [New method for measuring the distances between the nitroxide spin label and paramagnetic metal ions in macromolecules]. AB - A new method of estimation of the distance RLM between the nitroxide spin label (NSL) and the paramagnetic metal ions (PMI), such as Co2+, Ni2+, Cu2+, Mn2+, VO2+, Cr3+, Fe3+ is suggested. The influence of the longitudinal relaxation time T1 of the PMI on the line shape of the NSL at 77 degrees K has been studied. It was found that the efficiency of the dipole-dipole interaction between NSL and PMI depends strongly on the T1 value of the PMI. Measurements of the RLM for 4 spin-labelled proteins (haemoglobin, nitrogenase, cytochrome P450 and Ca2+ dependent ATPase) by three various methods have proved the correctness of the new method and also its simplicity. PMID- 6268968 TI - [Structural organization of human simian virus 40 chromosomes. I. Heterogeneity and composition of nuclear DNA-protein complexes at different stages of lytic infection]. AB - Extraction of the purified nuclei of SV40 infected cells reveals a heterogeneous set of viral DNA-protein complexes. Earlier, the authors have shown the possibility of nuclear particles extraction being indistinguishable from mature SV40 virions. In the present work, structural intermediates of virus maturation from free minichromosomes through replicative complexes to immature virion particles have been analyzed. The fractionation of viral complexes by non denaturing agarose gel electrophoresis has been employed. The protein composition of the complexes as determined by two-dimensional gel electrophoresis indicates that five histone fractions including H1 are present during minichromosome maturation to the chromosome of the mature virion. PMID- 6268961 TI - Mechanism of action of choleragen and E. coli heat-labile enterotoxin: activation of adenylate cyclase by ADP-ribosylation. PMID- 6268969 TI - [Construction of promoter-probe plasmid vector]. AB - A new plasmid vector, designated pBRS188 has been constructed for cloning of promoter-containing DNA fragments. This plasmid is a derivative of the E. coli drug-resistance plasmid pBR322 in which a small region (13 base pairs long) within the Tc promoter is eliminated. As a result of the alteration pBRS188 has lost the ability to confer Tc resistance to the host strain. Cloning of foreign DNA fragments, carrying promoters for E. coli RNA polymerase, into the unique EcoRI site of pBRS188 allows to isolate the recombinant TcR transformants. Our construction required the use of new techniques, involving partial hydrolysis of DNA fragments by E. coli DNA polymerase I in the presence of one deoxyribonucleosidetriphosphate and by nuclease S1. An important feature of this method is the ability to regenerate restriction endonuclease recognition sites at junctions of DNA fragments. PMID- 6268970 TI - Viral infections of the fetus and the neonate. PMID- 6268972 TI - Nitrite converts 2-amino-alpha-carboline, an indirect mutagen, into 2-hydroxy alpha-carboline, a non-mutagen, and 2-hydroxy-3-nitroso-alpha-carboline, a direct mutagen. AB - 2-Amino-alpha-carboline [26148-68-5] which was isolated from a pyrolysate of soybean globulin and which was mutagenic to Salmonella typhimurium in the presence of a rat-liver microsomal fraction (S9 mix), was converted into non mutagenic 2-hydroxy-alpha-carboline by treatment with nitrite in acidic conditions. However, on prolonged treatment with nitrite and acid, 2-hydroxy alpha-carboline was further converted into a new mutagen which did not require S9 mix for exhibition of the mutagenicity. This direct-acting mutagen was found to be 2-hydroxy-3-nitroso-alpha-carboline by mass and proton magnetic resonance spectroscopies. PMID- 6268971 TI - Effect of glutathione and uridine 5'-diphosphoglucuronic acid on mutagenesis by benzo[a]pyrene and aflatoxin B1 in the Salmonella/microsome assay. AB - In the Salmonella/microsome plate or liquid assay, the addition of glutathione (GSH) and uridine 5'-diphosphoglucuronic acid (UDPGA), both cofactors for GSH-S transferases or UDPGA-transferases, altered the rat-liver microsome-mediated mutagenesis of benzo[a]pyrene (BP) and aflatoxin B1 (AFB). With either BP or AFB, an increased, unchanged or decreased number of revertant colonies of S. typhimurium was observed, depending on the substrate concentration, the source of rat-liver 9000 X g supernatant (S9), the time of incubation and the type of mutagenicity test (liquid or plate assay). Several factors responsible for quantitative changes in the pattern of BP and AFB metabolites under various assay conditions in vitro, which alter the overall mutagenic activity of the parent compound, are discussed. PMID- 6268973 TI - Further experiences with ketoconazole in the treatment of onychomycosis. PMID- 6268974 TI - Treatment of pityrosporum folliculitis with ketoconazole (R 41400). PMID- 6268975 TI - Pathology and probabilities: a new approach to interpreting and reporting biopsies. AB - Pathologists typically analyze biopsy specimens and report their opinions in a qualitative fashion. Clinical information, often fragmentary in character, is implicitly linked with the histologic findings, and interpretations are couched in ambiguous language: "consistent with," "highly suggestive of," "may represent," or "cannot exclude." Only pathognomonic or normal findings are reported in an unequivocal fashion. In this paper we compare the analysis of biopsy material by a conventional method and by a numerical, probabilistic technique. We suggest that applying a probabilistic technique can considerably improve the precision of tissue diagnosis and can greatly facilitate the communication of pathologists with clinicians and with each other. Probabilistic analysis is also likely to be of substantial value in improving the interpretation and reporting of x-ray and nuclear-medicine studies. PMID- 6268976 TI - Does mitotane reduce endogenous ACTH secretion? PMID- 6268977 TI - Glucocorticoid-suppressible hyperaldosteronism: a clue to the missing hormone? PMID- 6268978 TI - Beta-receptors in orthostatic hypotension. PMID- 6268979 TI - Anomalous postural aldosterone response in glucocorticoid-suppressible hyperaldosteronism. PMID- 6268981 TI - Silicone-induced splenomegaly: treatment of pancytopenia by splenectomy in a patient on hemodialysis. PMID- 6268980 TI - Integration of hepatitis B virus DNA into the genome of liver cells in chronic liver disease and hepatocellular carcinoma. Studies in percutaneous liver biopsies and post-mortem tissue specimens. AB - We used recombinant-DNA technology and gel electrophoresis to find hepatitis B virus DNA (HBV-DNA) in liver and tumor tissue from patients with hepatocellular carcinoma and chronic liver disease, and to study the integration of HBV-DNA into the genome of these tissues' cells. In 12 patients with hepatocellular carcinoma who had hepatitis B surface antigen (HBsAg) in their serum, integrated HBV-DNA was identified in the tumors; it was also found in tumors from three of eight patients who were seronegative for HBsAg but positive for antibody to HBsAg. In some cases, integrated HBV-DNA was also present in nontumorous liver tissue that had the same hybridization pattern or one different from that of the tumor. In five carriers of HBsAg who had evidence of the carrier state and chronic liver disease for less than two years, HBV-DNA was present but not integrated in liver tissue. In the two patients who had carried HBsAg for more than eight years, HBV DNA was integrated into the host genome. These data suggest that integration of HBV-DNA into hepatocytes occurs during the course of persistent HBV infection and precedes development of gross neoplasm. PMID- 6268982 TI - Hepatic sodium-potassium pump in obesity. PMID- 6268983 TI - A human onc gene homologous to the transforming gene (v-sis) of simian sarcoma virus. PMID- 6268984 TI - SV40 T antigen binds specifically to a cellular 53 K protein in vitro. PMID- 6268985 TI - Modulation of platelet shape and membrane receptor binding by Ca2+-calmodulin complex. PMID- 6268987 TI - Increased phosphotyrosine content and inhibition of proliferation in EGF-treated A431 cells. PMID- 6268986 TI - Genetic modification of potassium channels in Drosophila Shaker mutants. PMID- 6268988 TI - Expression of Tn9-derived chloramphenicol resistance in Bacillus subtilis. PMID- 6268989 TI - Gene families, hopeful monsters and the selfish genetics of dna. PMID- 6268990 TI - Dilute (d) coat colour mutation of DBA/2J mice is associated with the site of integration of an ecotropic MuLV genome. AB - The single endogenous DBA/2J ectropic provirus segregated concordantly with the dilute (d) coat colour mutation on chromosome 9 in 53/53 DBA/2J-derived recombinant inbred mouse strains and all seven inbred and mutant strains tested that carry the d allele. Analysis of DNA from a spontaneous DBA/2J d revertant (d+2J) showed that these mice lack ecotropic-specific MuLV DNA sequences and suggested that the dilute mutation resulted from integration of an ecotropic provirus into the mouse genome. PMID- 6268991 TI - Production of infectious Epstein--Barr virus in mouse lymphocytes. PMID- 6268992 TI - Glucocorticoids and benzo(a)pyrene had opposing effects on EGF receptor binding. PMID- 6268993 TI - [Epstein-Barr virus infection in the development of human tumors]. AB - The Epstein-Barr Virus (EBV) is the only infectious agent for which a close association with human malignant tumors has been clearly demonstrated. These tumors are one type of nasopharyngeal carcinoma which is frequent in parts of East Asia and the Burkitt lymphoma which predominantly occurs in parts of Africa and New Guinea. Nonetheless, the EBV is the causative agent of infectious mononucleosis (IM), a benign, self-limiting lymphoproliferative disease of adolescents. The major difference between the countries in which the EBV-induced tumors occur and those in which IM occurs is the late primary EBV infection in the latter, whereas primary infection with EBV occurs in the first year of life in the former. All theories of viral carcinogenesis have to explain the long latency period between primary infection and tumor growth and how an ubiquitous virus may be oncogenic. Thus, invariably, one has to assume a role of cofactors, which may be of cytogenetic nature or may be represented by additional infections or by chemical agents. Since most modern theories of carcinogenesis consider a multi-step development of tumors, the theory that infection with an ubiquitous virus at the right time of life represents one step to carcinogenesis seems to be tenable. PMID- 6268994 TI - Stimulation of prostaglandin E2-synthesis by noradrenaline in primary cell cultures from rabbit splenic pulpa is mediated by atypical alpha-adrenoceptors. AB - In primary cell cultures originating from rabbit splenic pulpa the effects of various adrenoceptor agonists on prostaglandin (PG)-synthesis were studied. The cells - microscopically identified as fibroblasts - released PGs into the medium: especially PGE2 besides small amounts of PGF2alpha and PGD2. Noradrenaline increased dose-dependently the amount of PGs released into the medium. Besides noradrenaline, only the catecholamines adrenaline and alpha-methylnoradrenaline strongly activated PG-synthesis. Other alpha-adrenoceptor agonists like the phenylethylamine and imidazoline derivatives were only weak agonists or completely ineffective. All adrenoceptor agonists without intrinsic activity in these cells antagonized the noradrenaline effect on PG-synthesis, the imidazolines being more potent antagonists than the phenylethylamines. The beta adrenoceptor agonist isoprenaline stimulated PG-synthesis at high concentration only. The effects of both noradrenaline and isoprenaline were inhibited by low concentrations of phentolamine phenoxybenzamine, but not by propranolol. The preferential alpha2-adrenoceptor antagonists yohimbine and rauwolscine were about 50 times more potent in blocking the noradrenaline effect on PG-synthesis than the more alpha1-specific antagonist corynanthine. However, prazosin, another alpha1-adrenoceptor antagonist, was about equipotent with yohimbine. It is concluded that noradrenaline elicits PG-synthesis in rabbit splenic fibroblasts via alpha-adrenoceptor stimulation. The alpha-adrenoceptor involved has properties which are different from those reported so far for alpha1- or alpha2 adrenoceptors. PMID- 6268995 TI - The effects of several muscarinic antagonists on pre- and postsynaptic receptors in the isolated rabbit heart. AB - In order to reveal possible differences between pre- and postsynaptic muscarine receptors, seven antagonists were tested for their affinities on these receptor sites in the rabbit isolated perfused heart. Methacholine was used as an agonist to inhibit the noradrenaline overflow evoked by electrical stimulation (3 Hz, 3 min) of the sympathetic nerves (presynaptic parameter) and to decrease the systolic tension development of the right atrium (postsynaptic parameter). The affinity of an antagonist was expressed as pA2. A decreasing order of potency was obtained with ipratropium, scopolamine, atropine, trihexyphenidyl, amitriptyline, and gallamine, both for pre- and postsynaptic responses. The antagonists acted competitively and their effects were reversible. Furthermore, for none of the drugs did the pA2 (pre) differ from the pA2 (post). With QNB (3-quinuclidinyl benzilate) a pA2 (post) of 11.65 was obtained. However, the affinity to presynaptic receptors could not be determined as a pA2 value due to the very prolonged exposure time required for the equilibrium with QNB and for that with methacholine in the presence of QNB. It is concluded that the antagonists employed do not reveal differences between pre- and postsynaptic muscarine receptors of the rabbit heart, in spite of their greatly varying chemical structure and their individual affinities ranging over 5 orders of magnitude. The findings confirm the view of a homogeneous muscarine receptor population characterized by functional parameters. PMID- 6268996 TI - alpha 1- and alpha 2-adrenoceptors in rat cerebral cortex: effect of frontal lobotomy. AB - Surgical noradrenergic denervation of the cortex via frontal lobotomy was used to destroy the noradrenergic nerve endings and thus give some insight into the distribution of alpha-adrenoceptors. Frontal lobotomy caused a reduction in noradrenaline content in rat cerebral cortex (2.1 +/- 0.4 ng/mg protein for lesioned side, 6.0 +/- 0.3 mg/mg protein for non-lesioned side), indicating an effective noradrenergic denervation. The differences in 3H-clonidine and 3H prazosin binding observed following surgery were a significant decrease in the number of alpha 2-adrenoreceptors (115.0 +/- 4.5 to 91.7 +/- 3.2 fmol/mg protein, n = 7, P less than 0.001) and a smaller but significant increase in the number of alpha 1-adrenoceptors (119.7 +/- 2.5 to 131.6 +/- 5.4 fmol/mg protein, n = 7, P less than 0.05) in the lesioned cortex. Results of this study indicate that alpha 2-adrenoceptors located on presynaptic noradrenergic terminals represent only a small proportion of the total alpha 2-adrenoceptors in rat cerebral cortex. PMID- 6268998 TI - Vasopressin stimulates release of beta-lipotropin and beta-endorphin in conscious rats as measured by radioimmunoassay of unextracted plasma. AB - Using a newly developed radioimmunoassay to determine the beta-endorphin-like immunoreactivity (beta-EI) in unextracted plasma, the effect of vasopressin injections on plasma beta-EI was investigated in conscious rats. Arginine vasopressin caused a dose-dependent increase of plasma beta-EI from 34.5 to 7.8 fmol ml--1 (n = 6) in vehicle-treated animals to 205.0 +/- 36.1 fmol ml--1 (n = 7) after injection of the highest vasopressin dose employed (486 ng/100 g b.w.). In view of the appreciable cross-reactivity of beta-lipotropin (beta-LPH) in the radioimmunoassay used, plasma was extracted and subjected to gel chromatography on a Sephadex G-50 column. On average, about 70% of the beta-EI co-eluted with human beta-LPH and about 30% with human beta-endorphin in plasma extracts obtained from both control and vasopressin-treated rats. No peripheral conversion of human beta-LPH occurred under the experimental conditions, since after i.v. bolus injection of human beta-LPH 97% of the beta-EI comigrated with human beta LPH during gel filtration. A similar blood pressure increase to that induced by the vasopressin injections, when elicited by noradrenaline or angiotensin II i.v., was not followed by an elevation of plasma beta-EI. These data indicate that vasopressin stimulates beta-lipotropin and beta-endorphin release into the systemic circulation in vivo. PMID- 6268997 TI - Regulation of alpha 1-adrenoceptors in the cerebral cortex of the rat by thyroid hormones. AB - The influence of thyroid hormones on the concentration and properties of alpha 1 adrenoceptors in a crude membrane fraction obtained from the rat cerebral cortex was investigated using the [3H]-WB 4101 binding assay. Animals were made hypothyroid by feeding 6-propyl-2-thiouracil for 8 weeks. Hyperthyroidism was induced by triiodothyronine injections (50 microgram/100 g body weight) for 9 days. 1. The binding of [3H]-WB 4101 was saturable and of high affinity in controls as well as in hyper- and hypothyroid animals. The maximal number of binding sites (Bmax), which amounted to 95 fmol/mg protein in control animals, was increased by 27% in cortical membranes from hyperthyroid rats and reduced by 23% in the hypothyroid group. 2. The reduction in [3H]-WB 4101 binding due to 6 propyl-2-thiouracil feeding was reversible by triiodothyronine treatment. 3. Dissociation constants (KD) calculated from saturation experiments (0.25 nM) or kinetic data (0.21 nM) remained unchanged in altered thyroid states. 4. Inhibition of [3H]-WB 4101 binding by adrenergic agonists and antagonists revealed no differences between euthyroid and hypothyroid animals. The higher affinity of prazosin to the binding sites compared with yohimbine indicated that [3H]-WB 4101 predominantly labeled alpha 1-adrenoceptors. It is concluded that thyroid hormones regulate the number of alpha 1-adrenoceptors in membranes of the rat cerebral cortex, leaving their affinities unchanged. PMID- 6268999 TI - The site of action of muscle relaxant purine nucleosides. AB - The effects of a series of purine nucleosides, including the novel marine natural product 1-methylisoguanosine, have been examined on muscle relaxation in conscious animals and on spinal reflexes and neuromuscular transmission in mice anaesthetized with sodium pentobarbitone. 1-Methylisoguanosine (5--15 mumol kg- 1) and 2-chloroadenosine (1--5 mumol kg--1), both of which cause muscle relaxation in conscious animals, depressed both mono- and polysynaptic spinal reflexes but did not affect neuromuscular transmission. At much higher doses (300 mumol kg--1) both compounds did depress neuromuscular transmission. Adenosine and 1-methyladenosine did not produce muscle relaxation in conscious animals and only slightly depressed polysynaptic reflexes at the highest doses tested (300 mumol kg--1). Theophylline 50 mumol kg--1 enhanced polysynaptic reflexes and antagonized the depression of these reflexes by 1-methylisoguanosine. Neither adenosine nor 1-methylisoguanosine affected the development of tension by isolated diaphragm muscles in vitro. It is concluded that the muscle relaxant purine nucleosides 2-chloroadenosine and 1-methylisoguanosine produce their effects primarily by depressing activity in the central nervous system. Transmission at the neuromuscular junction is not affected at doses in the range of those producing muscle relaxation. PMID- 6269000 TI - In vitro studies on 6-fluoronoradrenaline at several peripheral sympathetic neuroeffector junctions. AB - A comparison of the effects of noradrenaline and 6-fluoronoradrenaline has been made at several peripheral sympathetic neuroeffector junctions. In the rat vas deferens preparation in the presence of 1 microM cocaine, 6-fluoronoradrenaline was found to be about 9 times more potent than noradrenaline as an agonist at presynaptic inhibitory alpha 2- adrenoceptors. In the rabbit aorta, 6 fluoronoradrenaline had approximately one tenth of the potency of noradrenaline in stimulating the postsynaptic alpha 1-adrenoceptors. Furthermore 6 fluoronoradrenaline, in contrast to previous reports, appears to be a substrate for the neuronal uptake process since exposure to cocaine potentiated the inhibition of the twitch response of the vas deferens by 6-fluoronoradrenaline. In addition, 6-fluoronoradrenaline increased the spontaneous outflow of radioactivity from rabbit pulmonary artery strips prelabelled with 3H noradrenaline and this increase was blocked by cocaine (30 microM). These results demonstrate that 6-fluoronoradrenaline is a preferential alpha 2-adrenoceptor agonist which is a substrate for the neuronal uptake process in peripheral sympathetically innervated smooth muscle preparations. PMID- 6269001 TI - Quercetin inhibits tyrosine phosphorylation by the cyclic nucleotide-independent, transforming protein kinase, pp60src. AB - The bioflavonoid quercetin is a potent inhibitor of a cyclic nucleotide independent, tumor virus-coded protein kinase which phosphorylates tyrosine residues and acts as a cellular transforming protein. Half-maximal inhibition of the protein kinase occurred at 3-4 microM quercetin whereas rutin was much less effective. The finding, that quercetin inhibits a cyclic nucleotide-independent protein kinase activity, may provide clues to the diverse pharmacological effects of the bioflavonoids. PMID- 6269002 TI - 3H-(-)-Bupranolol, a new beta-adrenoceptor radioligand: characterization of its binding to kitten heart beta-adrenoceptors. PMID- 6269003 TI - Smooth muscle of rabbit aorta contains alpha 1-but not alpha 2-adrenoceptors. AB - We have investigated the residual contractile response to noradrenaline remaining after phenoxybenzamine (3 x 10(-7) mol/l) in rabbit aorta, since it has been reported that phenoxybenzamine at low doses completely and irreversibly blocks alpha 1-but not alpha 2-adrenoceptors. The contraction elicited by noradrenaline slowly recovered with time after it had been almost abolished by phenoxybenzamine. This residual response was blocked by the alpha 1-selective antagonist prazosin (3 x 10(-8) mol/l) but not by the alpha 2-selective antagonist rauwolscine (3 x 10(-7) mol/l). The results confirm that the smooth muscle of rabbit aorta contains alpha 2-but not alpha 2-adrenoceptors. PMID- 6269005 TI - [Posttraumatic panophthalmia caused by clostridium perfringens]. PMID- 6269006 TI - Sister chromatid exchange analysis in a 61 year-old female using various medications. PMID- 6269004 TI - The effects of muscimol and picrotoxin injections into the cat substantia nigra. AB - The behaviour of cats after unilateral injections of muscimol, picrotoxin and bicuculline into the posterior and lateral parts of the substantia nigra was observed. The antagonism between muscimol and picrotoxin was limited to some effects of the drugs: (1) muscimol-induced sniffing, licking and enhanced locomotor activity was attenuated by picrotoxin in contrast to the muscimol induced contralateral turning which was even enhanced by picrotoxin; (2) picrotoxin-induced balance disorders as well as characteristic motor disturbances in the hind legs remained unaffected following an additional treatment with muscimol. Furthermore, subcutaneously given apomorphine did not affect the picrotoxin-induced balance and hind leg disorders, although the apomorphine induced stereotyped behaviour itself was enhanced and suppressed by intranigral administration of muscimol and picrotoxin respectively. The conclusion is reached that there are at least two distinct populations of GABA receptors within the substantia nigra: one group controlling or being controlled by dopaminergic neurons and one group operating fully independently of the former neurons. The similarities to experiments on rats are stressed. The mechanism underlying the muscimol-resistant picrotoxin-induced effects (balance disorders and motor disturbance of the hind legs) is discussed. PMID- 6269007 TI - [Habituation of direct cortical responses in the cat]. AB - Acute experiments on cats under barbiturate anesthesia were made to study a gradual decrease of direct cortical responses in different cortical areas. It is found that during repetitive stimulation of the surface of association cortical areas the direct responses undergo all the changes characteristic of habituation. In the primary projection cortical areas the direct responses were stable and no habituation was observed. Reasons for differences in the changes of direct responses in different cortical areas are discussed. In a series of experiments an isolated cortical slab was prepared in primary cortical area. Direct responses habituated under such conditions in a way similar to the habituation in the association cortical areas. It is suggested that primary projecting areas receive strong ascending activating influences from subcortical structures which act as a response sensitizer. PMID- 6269008 TI - [Neuronal analysis of the projection of the caudal trigeminal nucleus to the nucleus of the facial nerve in cats]. AB - Peculiarities of the trigeminal nucleus caudalis neurons which are projected to the facial nucleus were studied by microelectrode recording in cats. It is shown that the mentioned neurons are localized predominantly in ventral parts of the trigeminal nucleus caudalis and adjacent lateral reticular formation. Mono- and polysynaptic activation of efferent trigeminal neurons to pyramidal impulsation is described. Repetitive discharges of these neurons to stimulation of their axons, direct stimulation of the trigeminal nucleus caudalis as well as to that of the pyramidal tract and facial nerve are recorded. The significance of the obtained data in the light for the understanding of the synaptic mechanisms of regulation of facial motoneurons activity is discussed. PMID- 6269009 TI - [Retuning of segmental responses to peripheral stimulation during fictive locomotion in cats]. AB - Segmental reflex responses of the lumbosacral spinal cord to peripheral afferent stimulation were investigated in immobilized decorticated cats before and during fictitious locomotion. Appearance of fictitious locomotion was accompanied by an increase of the N1 component of the dorsal cord potential and of the dorsal root potential. Modulation of these responses depending on the phase of fictitious locomotion was observed against a background of their tonic increase. The N1 component and dorsal root potential had larger amplitudes when they appear at the end of the "extensor" phase and at the beginning of the "flexor" phase and smaller amplitudes when they were evoked at the end of the "flexor" phase and at the beginning of the "extensor" phase. Poly- and monosynaptic reflex responses of motoneurons revealed the same phase dependence during fictitious locomotion. Mechanisms and physiological significance of the revealed retuning of segmental reflex responses are discussed on the basis of the obtained data. PMID- 6269010 TI - [Application of a triple barrier model to describe the energy profile of a calcium channel in the neuronal membranes of mollusks]. AB - On the basis of measurements of the current-voltage characteristic shifts in the neuronal membrane of Helix pomatia the density and binding constants are calculated for charged groups of its outer surface. The obtained values are: sigma = 0.23 e-/nm2, KCa = 70 M-1, K Sr = 40 M-1, KBa = 20 M-1. These data are used for determination of near-membrane concentration of the carrier ions in the extracellular solution and true location of the current-voltage characteristics of calcium channels relative to the potential axis. The energy profile of calcium channel is calculated using a three-barrier model. The values of dissociation constants for calcium and barium ions with an outer binding site are equal to 10 and 91 mmol/l, respectively. The pK titration value for this site is 5.8. A conclusion is made that the value of inward ion current is determined mainly by the interaction energy between the carrier ion and the outer binding site which contains, probably, only one carboxylic group. The suppression of this current occurs under such a value of intracellular calcium concentration, when the occupation number of the inner binding site is considerably less than unity, and may be associated with an indirect influence of these ions through the system of cyclic nucleotides. PMID- 6269011 TI - [ACTH and corticosteroid treatment for neurological diseases (author's transl)]. PMID- 6269012 TI - Effect of lithium and sodium ions on opiate- and dopamine-receptor binding. AB - The effects of lithium and sodium were studied in the corpus striatum and cerebral cortex of rats. Lithium was inhibitory at low concentrations but at 20 mM it increased the binding of [G-3H]naloxone (specific activity 15.6 Ci/mmol). Sodium stimulated the high-affinity binding of this compound. Membranes obtained from the rats treated with lithium showed lower specific binding of both [3H]naloxone and [3H]DHM. Binding of [3H]d-alanine Leu-enkephalin was not changed in the brains of lithium-treated rats, but that of [3H]-spiroperidol was lowered. Cerebral cortex and striatum of lithium-treated rats had a decreased apparent dissociation constant and a lower receptor concentration of naloxone binding sites. PMID- 6269013 TI - Endogenous inhibitors of Na+-independent [3H]GABA binding to crude synaptic membranes. AB - The characteristics of the Na+-independent high-affinity binding of [3H]GABA to various types of crude synaptic membranes (CSM) prepared from rat brain cortex were studied. In freshly prepared CSM the content of GABA was so high that the high-affinity [3H]GABA binding could not be determined. In contrast when the frozen-thawed CSM were incubated at 37 degrees for 30 min with or without Triton X-100 or phospholipase C and then washed repeatedly, there was a virtual disappearance of GABA from the supernatant extracts and the binding constants of [3H]GABA to CSM could be determined. Two apparent populations of [3H]GABA binding sites, one with a low- and the other with a high-affinity constant, were detected. The ratio of the number of high- to low-affinity binding sites varies with the method used to prepare the membranes. The lowest value of this ratio was observed with membranes incubated at 37 degrees for 30 min. However, when frozen thawed CSM were treated with 0.05% Triton X-100 repeatedly, the ratio of the number of high- to low-affinity binding sites increased progressively. This increase in ratio is due to a selective increase in the number of the high affinity sites without significant changes in the number of the low-affinity sites. The extent of the increase in the number of sites that bind [3H]GABA with high affinity after repeated Triton X-100 treatments was paralleled by a decrease of an endogenous protein which inhibits GABA binding. The reapplication of this endogenous material to membranes repeatedly treated with Triton X-100 reduces the number of high-affinity binding sites for [3H]GABA to values similar to those measured in membranes that were not treated with Triton X-100. The inhibitory preparation extracted from CSM incubated with Triton X-100 was shown to be free of GABA or phospholipids. The gel filtration chromatography reveals the presence of two molecular forms of the inhibitor; of these, the high-molecular-weight material fails to bind GABA, whereas the low-molecular-weight material appears to bind GABA. The high-molecular-weight endogenous inhibitor has been termed GABA modulin. PMID- 6269014 TI - Intracytoplasmic rod-like inclusions in caudate nucleus. AB - A number of intraneuronal inclusion bodies have been described as incidental findings, but the intracytoplasmic rod-like inclusions in the caudate nucleus are not widely known. They are called 'alcoholic hyaline-like bodies', because they were first reported in two patients with chronic alcoholism and the inclusions were likened to Mallory bodies of alcoholic liver. However, we have found that their prevalence was not significantly different in alcoholics with or without liver damage, in individuals with miscellaneous neurological disorders and in a control group of patients without neurological or hepatic disease. It was therefore concluded that these inclusions represent a non-specific finding. PMID- 6269015 TI - Non-specific, non-selective and mild increase in the latency of pentylenetetrazol seizures produced by large doses of the putative endogenous ligands of the benzodiazepine receptor. PMID- 6269016 TI - Pineal Tumors: clinical diagnosis, with special emphasis on the significance of pineal calcification. AB - The clinical presentations, findings of neuroradiological examinations, laboratory findings, pathological diagnoses, methods of treatment, and results of follow-up of 43 cases of pineal tumor collected at the Nagoya University Hospital from 1958 to 1979 are reviewed. The definitions of calcification of the pineal body and of pineal tumor are given. There is a significant difference in the incidence of calcification of the pineal body between pineal teratomas and pineal germinomas. Although there is a 100% rate of calcification of the pineal body in cases of pineal germinoma, the rate is very low in cases of pineal teratoma; calcification appears in only a small percentage of the cases of teratoma mixed with germinoma or embryonal carcinoma, or both. In male patients with suprasellar germinoma, there is a high frequency of an associated pineal calcification. No pineal calcification is seen in cases of basal ganglia germinoma. The computed tomographic (CT) findings of pineal teratoma and germinoma are characteristic. CT scanning is superior for early diagnosis of suprasellar and basal ganglia germinomas. PMID- 6269017 TI - Development of pseudotumor cerebri after the removal of an adrenocorticotropic hormone-secreting pituitary adenoma: case report. AB - A patient with Cushing's disease developed intracranial hypertension 1 month after the removal of an adrenocorticotropic hormone-secreting pituitary adenoma. A computed tomographic scan demonstrated normal ventricles and no intracranial mass, establishing the diagnosis of pseudotumor cerebri. The elevated intracranial pressure was apparently consequent to an abrupt reduction in circulating corticosteroids. The development of pseudotumor cerebri after the correction of endogenous hypercortisolism has not been reported previously. This potential complication of the surgical treatment of Cushing's disease can be managed with prompt recognition and appropriate treatment of the syndrome. PMID- 6269018 TI - Feeding and defensive conditioned reflexes to electrical stimulation of different formations of the limbic system. PMID- 6269019 TI - Changes in input resistance of a cortical neuron and in threshold of stimulation of its electrically excitable membrane by a depolarizing current during habituation. PMID- 6269020 TI - Ionic mechanisms of analog-code conversion in nerve-fiber membrane. PMID- 6269021 TI - A polarization-electrotonic hypothesis of formation of simple forms of temporary connection. PMID- 6269022 TI - [Effects of calcium antagonists (verapamil and nifedipine) on blood levels of calcium and cyclic AMP in humans]. PMID- 6269023 TI - [Diverticular disease of the colon]. PMID- 6269024 TI - [Autoimmunity and polyendocrinopathic syndromes]. PMID- 6269025 TI - [Adrenal cortex response to prolonged stimulation, in eumenorrheal patients with hypertrichosis, as a function or prolactin levels]. PMID- 6269026 TI - A "receptor" for protons in small neurons of trigeminal ganglia: possible role in nociception. AB - Neurons of the rat's trigeminal ganglion were enzymatically isolated and investigated under the conditions of intracellular perfusion and voltage clamp. Recently discovered proton-activated sodium conductance was found in about half of the neurons. The majority of these proton-sensitive neurons (74%) were less than 26 micrometer in diameter, whereas most of the proton-insensitive cells (75%) were larger than 26 micrometer in diameter. The possibility is discussed that the small proton-sensitive neurons may participate in nociception. PMID- 6269027 TI - Indoleamine-accumulating cells and dopaminergic cells are distributed similarly in carp retina. AB - Carp (Cyprinus carpio) retinas were processed for simultaneous visualization of dopaminergic (DA) and indoleamine-accumulating (ID) cells in flat-mounts under fluorescence microscope. A mixture of 5 micrograms noradrenaline (NA) and 5 micrograms 5,6-dihydroxytryptamine (5,6-DHT) was injected intravitreally into the eyes 2 h before enucleation. The spatial distribution and density were compared between NA-loaded DA-cells (greenish fluorescence) and 5,6-DHT-loaded ID-cells (yellowish). The two classes of cells were found to distribute similarly in a mixed fashion. Their densities were higher in the peripheral region than in the rest and extremely high at the retinal margin. Where the densities were higher, the size of cell bodies tended to be smaller. DA-cells were generally larger than ID-cells. Those cells, located in the intermediate and peripheral regions, appeared to be arranged in radial rows originating at the optic disc. PMID- 6269028 TI - Medullary raphe lesions do not reduce descending inhibition of dorsal horn neurones of the cat. AB - In anaesthetized cats spinal cold block was used to examine the effects of medullary raphe lesions on the responses of dorsal horn neurones to impulses in unmyelinated primary afferents. Lesions failed to affect these responses, casting doubt on the importance of this region and its serotonergic spinal projections to the control of nociceptive transmission at the spinal level. PMID- 6269029 TI - Comparison of [3H]clonidine and [3H]guanfacine binding to alpha 2 adrenoceptors in membranes from rat cerebral cortex. AB - [3H]Clonidine and a new phenylacylguanidine antihypertensive drug, [3H]guanfacine, bind with a high affinity to alpha 2 adrenoceptors in membranes from rat cerebral cortex. Dissociation curves for [3H]clonidine binding indicated the presence of high and low affinity binding sites, whereas with [3H]guanfacine, two components could be distinguished only with difficulty; the major part of the binding being to a high affinity component. Saturation experiments revealed that both ligands bind with similar high affinity but that [3H]guanfacine labels twice the number of sites labeled by [3H]clonidine. PMID- 6269030 TI - Lamina-specific alteration of C-fibre evoked activity by morphine in the dorsal horn of the rat spinal cord. AB - The effect of systemic morphine (5 mg/kg) on the C-fibre evoked activity in the dorsal horn of decerebrate spinalized rats has been investigated. Activity in units recorded from lamina 5 was inhibited in a naloxone-reversible fashion by morphine. However, morphine produced variable changes in the C-evoked activity of units recorded within the substantia gelatinosa, some units showing excitation, some inhibition and some an alteration in the timing and pattern of the C-evoked activity. PMID- 6269031 TI - Peptides isolated from the venom of Conus geographus block neuromuscular transmission. AB - The effects of a mixture of two peptides (GI and GII), purified from the venom of the marine gastropod, Conus geographus, were studied on neuromuscular transmission in the isolated mouse phrenic nerve--diaphragm and frog sciatic nerve--sartorius muscles. The GI--GII mixture rapidly blocked nerve-evoked contractions of the mouse diaphragm at bath concentrations greater than or equal to 0.2 microM but had no effect on contractions elicited by direct muscle stimulation. Paralytic concentrations of GI--GII had no significant effect on the compound nerve action potential of the bullfrog sciatic nerve. Similar concentrations of GI--GII produced a rapid reduction of endplate potential (epp) and miniature endplate potential amplitudes, apparently by a postsynaptic effect because the decrease in epp amplitude produced by subparalytic doses was not accompanied by significant alteration in the epp quantal content. The GI--GII mixture also inhibited [125I]alpha-bungarotoxin binding to endplate regions of the mouse diaphragm in a dose-dependent manner and was at least 10 times more potent than d-tubocurarine. We conclude that the blockage of vertebrate neuromuscular transmission by GI--GII is in part due to antagonism of acetylcholine binding to its receptor at motor endplates. PMID- 6269032 TI - Receptor autoradiography with tritium-sensitive film: potential for computerized densitometry. AB - Benzodiazepine receptors mounted tissue sections of brain were localized by autoradiography using a tritium-sensitive sheet film (3H-Ultrofilm, LKB). The use of the film had many advantages compared to a previous technique utilizing emulsion-coated coverslips. A major advantage is the adaptability of the film to microdensitometric techniques for measurement of receptors. The densitometry can be carried out by computerized, color-coded image analysis. PMID- 6269034 TI - Neurological disease in folic acid deficiency. PMID- 6269033 TI - Effect of vitamin E on prostanoid biosynthesis. PMID- 6269035 TI - Sarcomas and related neoplasms of the uterine corpus--a brief review of their natural history, prognostic factors, and management. PMID- 6269036 TI - Assessment of pituitary function. PMID- 6269037 TI - The renin-angiotensin system in pregnancy. PMID- 6269038 TI - Oral contraceptives and postmolar trophoblastic disease. AB - One hundred patients, managed for molar pregnancy at the New England Trophoblastic Disease Center, were selected at random to determine if the contraceptive method following molar evacuation influenced the incidence of postmolar trophoblastic disease. Following molar evacuation, 58 (58%) patients used oral contraceptives and 42 (42%) patients used barrier methods (foam, condom, and/or diaphragm). Postmolar trophoblastic disease developed in 11 (18.9%) patients using oral contraceptives and in 6 (14.3%) patients using barrier methods (P greater than .10). The mean human chorionic gonadotropin (hCG) regression time after molar evacuation was 7.0 weeks in patients using oral contraceptives and 7.2 weeks in patients using barrier methods. The 2 groups of patients were comparable in age, gravidity, molar histology, pretreatment hCG titers, and exposure to prophylactic chemotherapy. Oral contraceptives do not appear to increase the risk of postmolar trophoblastic tumors and therefore may be safely prescribed after molar evacuation during the entire interval of gonadotropin monitoring. PMID- 6269039 TI - [Role of a mixed herpes-viral and tubercular allergy in the pathogenesis of ophthalmic herpes]. PMID- 6269040 TI - [Dynamics of the specific antibody titers in eye diseases of influenzal and enteroviral etiology]. PMID- 6269041 TI - [Plasma aldosterone--normal values in children, effect of stress and ACTH, nutrition effect and daily rhythm in newborn infants]. PMID- 6269042 TI - Infant pneumonitis associated with cytomegalovirus, Chlamydia, Pneumocystis, and Ureaplasma: a prospective study. AB - In a prospective study of 104 infants between 1 and 3 months of age hospitalized with pneumonitis, 65 (63%) had evidence of infection with one or more potential respiratory pathogens. Single infections were noted in 48 (74%) whereas mixed infections occurred in 17 (26%) of 65 infected infants. The four most common infections were Chlamydia trachomatis (15/59, 25%), Ureaplasma urealyticum (8/38, 21%), cytomegalovirus (21/104, 20%), and Pneumocystis carinii (19/104, 18%). In sharp contrast, the incidence of these infections in control infants was 0% (0/25), 4% (2/49), 3% (3/97), and 0% (0/64), respectively. The clinical, radiologic, and laboratory characteristics of the pneumonitis syndrome associated with Chlamydia, cytomegalovirus, and Pneumocystis were indistinguishable from each other. Patients with mixed infections had a more severe pneumonitis as measured by the occurrence of apnea and the need of oxygen therapy an mechanical ventilation. The patients enrolled in this study are being followed-up to determine the longitudinal course of these infections. PMID- 6269043 TI - The role of prostaglandins in the alpha- and beta-adrenoceptor mediated renin release response to graded renal nerve stimulation. AB - The role of prostaglandins in the renin release response to renal nerve stimulation (RNS) at different intensities was examined in the anaesthetized dog. The animals were divided into two groups receiving either low or high level RNS, defined by the frequencies of stimulation producing reduction in renal blood flow by 5% or less and 50%. Indomethacin or diclofenac sodium (5 mg/kg i.v.), prostaglandin synthesis inhibitors, did not affect the renin release response to low level RNS but decreased the renin release response to high level RNS by 31 +/ 8% (P less than 0.01). Addition of metoprolol, (0.5 mg/kg i.v.) beta-1 adrenoceptor antagonist, to indomethacin or diclofenac sodium resulted in a greater reduction (68 +/- 6% P less than 0.01) of the renin release response to high level RNS compared to that produced by either drug alone. Metoprolol, alone, reduced the renin release response to high level RNS by 37 +/- 14% (P less than 0.05). Phenoxybenzamine (0.6 microgram . kg-1 . min-1), alpha-adrenoceptor antagonist, into the renal artery practically abolished the renal vasoconstrictor response to high level RNS and reduced the renin release response by 50 +/- 7% (P less than 0.01). Addition of metoprolol to phenoxybenzamine practically abolished the renal vasoconstrictor response and the renin release response to high level RNS; 94 +/- 4% (P less than 0.01). Addition of phenoxybenzamine to indomethacin or diclofenac sodium practically abolished the renal vasoconstrictor response to high level RNS but did not produce any greater reduction of the renin release response than that produced by either drug alone. These findings suggest that low level RNS results in renin release which is not dependent on prostaglandins. High level RNS results in renin release which is partly mediated by beta-1 adrenoceptors and partly related to alpha-adrenoceptors mediated renal vasoconstriction. Prostaglandins are not involved in the renin release deriving from alpha-adrenoceptor mediated renal vasoconstriction. PMID- 6269044 TI - The effect of reduced calcium on quantal unit current and release at the crayfish neuromuscular junction. AB - Excitatory postsynaptic currents (EPSCs) were recorded extracellularly from large muscle fibers by means of 'patch clamp' electrodes. Compared to usual extracellular recordings, better signal/noise ratio and temporal stability were achieved. In the range of extracellular calcium concentrations [Ca]0 between 2.7 and 13.5 mmol/l (normal), the average amplitude of the EPSC increased more than proportional to [Ca]0. The unit quantum current, C1, and the average release rate, m, were determined from EPSCs and also from spontaneous sEPSCs, using both Poisson and binomial statistics. The main effect of [Ca]0 was on m: at different synaptic sites m depended on the second to fourth power of [Ca]0. In terms of binomial parameters, the release probability p is the [Ca]0-dependent one. In addition, reduction of [Ca]0 from 13.5 to 2.7 mmol/l decreased the unit quantum C1 consistently to 60%; simultaneously the rise and decay of EPSCs and sEPSCs were shortened by 10-20%. [Ca]0 thus has strong presynaptic effects on the release probability, but in addition smaller ones on the postsynaptic channel characteristics. PMID- 6269045 TI - [Gas formation in the hepatomas treated by hepatic arterial embolisation --a report of three cases (author's transl)]. PMID- 6269046 TI - [Is there a preventive method useful for cerebral metastases of anaplastic bronchial cancers?]. PMID- 6269047 TI - [Serum SV40 T-antibodies in cerebral tumors of various types. Negative study in 84 subjects]. PMID- 6269048 TI - Structure of nucleosome core particles containing uH2A (A24). AB - We have purified uH2A (A24) and reconstituted it, in place of H2A, into high molecular weight nucleohistone containing the core histones and DNA. uH2A containing core particles were then prepared by nuclease digestion and studies on these particles were carried out. We show that two uH2A molecules can be accommodated within a core particle. We also show that the presence of two uH2A molecules in a core particle does not alter significantly either the pattern or the rate of DNase I digestion as compared to both reconstituted and native core particles. Finally, we show that HMG proteins 14 and 17 can bind to uH2A containing core particles. We conclude that uH2A has little influence on structure at the level of individual nucleosomes. PMID- 6269049 TI - Terminal uridylyl transferase of Vigna unguiculata: purification and characterization of an enzyme catalyzing the addition of a single UMP residue to the 3'-end of an RNA primer. AB - An enzyme which catalyzes the addition of a single UMP residue from UTP to the 3' end of an RNA primer and which is referred to as terminal uridylyl transferase (TUT) has been extensively purified from the membrane fraction of vigna unguiculata leaves. The purification procedure involved (i) solubilization by cation depletion (ii) DEAE-Sepharose CL-6B column chromatography (iii) affinity chromatography of poly(U)-Sepharose 4B and (iv) glycerol gradient centrifugation. The molecular weight of the native enzyme was approximately 50,000 as determined by velocity sedimentation. Under conditions that were optimal for UMP incorporation (5 mM Mg2+, low salt, 30 degrees C) TUT displayed a marked specificity for UTP as substrate, was unable to incorporate deoxyribonucleoside triphosphates and required a single-stranded oligo- or polyribonucleotide as primer. When oligoA20, tRNAasp of E. coli or alfalfa mosaic virus RNA 4 were used as primers at various substrate to primer ratio's, the vast majority of the product appeared to consist of primer molecules elongated with a single UMP residue as shown by polyacrylamide gelelectrophoresis and nearest neighbour analysis. We believe TUT to be a novel enzyme which has not been reported before and which may be a feasible tool in RNA sequencing as it enables the specific 3' terminal labeling of RNA molecules. PMID- 6269050 TI - Quantitation of DNase I sensitivity in Xenopus chromatin containing active and inactive globin, albumin and vitellogenin genes. AB - The disappearance of defined restriction fragments of the beta 1-globin, an albumin and the A1 vitellogenin gene was quantitated after DNase I digestion and expressed by a sensitivity factor defined by a mathematical model. Analysis of naked DNA showed that the gene fragments have similar but not identical sensitivity factors. DNase I digestion of chromatin revealed for the same gene fragments sensitivity factors differing over a much wilder range. This is correlated to the activity of the genes analyzed: the beta 1-globin gene fragment is more sensitive to DNase I in chromatin of erythrocytes compared to hepatocytes whereas the albumin gene fragment is more sensitive to DNase I in chromatin of hepatocytes. The A1 vitellogenin gene has the same DNase I sensitivity in both cell types. Comparing the DNase I sensitivity of the three genes in their inactive state we suggest that different chromatin conformations may exist for inactive genes. PMID- 6269051 TI - Estrogen induces tissue specific changes in the chromatin conformation of the vitellogenin genes in Xenopus. AB - Nuclei from male Xenopus liver were digested extensively with DNase I and the residual amount of the four vitellogenin genes measured by hybridization with a moderate excess of vitellogenin cDNA. The saturation value was about twofold lower in chromatin isolated from liver cells of estrogen treated than from untreated males or from erythrocytes. Analyzing the disappearance of several defined restriction fragments specific for the A1 and A2 vitellogenin genes, after limited digestion with DNase I, suggested that the entire A1 and A2 vitellogenin genes are about twofold more sensitive to DNase I in chromatin of hepatocytes isolated from estrogen treated than from untreated males. Using the same assay no change in the DNase I sensitivity of the two vitellogenin genes in erythrocyte chromatin was observed. Analysis of the beta 1-globin and an albumin gene demonstrated that the DNase I sensitivity of these genes in both cell types is not altered by estrogen. All these data indicate that estrogen stimulation results in an increased DNase I sensitivity specific for the vitellogenin genes in hepatocytes. PMID- 6269052 TI - Restriction enzyme digestion of hemimethylated DNA. AB - Hemimethylated duplex DNA of the bacteriophage phi X 174 was synthesized using primed repair synthesis is in vitro with E. coli DNA polymerase I followed by ligation to produce the covalently closed circular duplex (RFI). Single-stranded phi X DNA was used as a template, a synthetic oligonucleotide as primer and 5 methyldeoxycytidine-5'-triphosphate (5mdCTP) was used in place of dCTP. The hemimethylated product was used as substrate for cleavage by various restriction enzymes. Out of the 17 enzymes tested, only 5 (BstN I, Taq I, Hinc II, Hinf I and Hpa I) cleaved the hemimethylated DNA. Two enzymes (Msp I and Hae III) were able to produce nicks on the unmethylated strand of the cleavage site. Msp I, which is known to cleave at CCGG when the internal cytosine residue is methylated, does not cleave when both cytosines are methylated. Another enzyme, Apy I, cleaves at the sequence CCTAGG when the internal cytosine is methylated, but is inactive on hemimethylated DNA in which both cytosines are methylated. Hemimethylated molecules should be useful for studying DNA methylation both in vivo and in vitro. PMID- 6269053 TI - Characterization of the beta-lactamase promoter of pBR322. AB - The beta-lactamase promoter of pBR322, derived from Tn3, has been characterized using several techniques. The transcription initiation site is located 35 base pairs from the translation initiation codon of beta-lactamase. The mRNA produced in vitro has a 5' pppGpA terminus. RNA polymerase bound at this start site protects a region from about -50 to +20 from DNase I cleavage using the footprinting technique. RNA polymerase binds rapidly to the beta-lactamase promoter. The half-time of association is less than one-half minute. The half time of dissociation is approximately 6 hr. A study of the binding of RNA polymerase at different temperatures showed a large change between 11 degrees and 15 degrees C. Comparison of these parameters with those reported for other promoters is discussed. PMID- 6269054 TI - Sequence arrangement of the rRNA genes of the dipteran Sarcophaga bullata. AB - Velocity sedimentation studies of RNA of Sarcophaga bullata show that the major rRNA species have sedimentation values of 26S and 18S. Analysis of the rRNA under denaturing conditions indicates that there is a hidden break centrally located in the 26S rRNA species. Saturation hybridization studies using total genomic DNA and rRNA show that 0.08% of the nuclear DNA is occupied by rRNA coding sequences and that the average repetition frequency of these coding sequences is approximately 144. The arrangement of the rRNA genes and their spacer sequences on long strands of purified rDNA was determined by the examination of the structure of rRNa:DNA hybrids in the electron microscope. Long DNA strands contain several gene sets (18S + 26S) with one repeat unit containing the following sequences in order given: (a) An 18S gene of length 2.12 kb, (b) an internal transcribed spacer of length 2.01 kb, which contains a short sequence that may code for a 5.8S rRNA, (c) A 26S gene of length 4.06 kb which, in 20% of the cases, contains an intron with an average length of 5.62 kb, and (d) an external spacer of average length of 9.23 kb. PMID- 6269055 TI - Penicillinase from Bacillus licheniformis: nucleotide sequence of the gene and implications for the biosynthesis of a secretory protein in a Gram-positive bacterium. AB - The gene for the penicillinase from B. licheniformis has been cloned in a functional stat on a 1.5 kb DNA fragment and its nucleotide sequence has been determined. A sequence of 307 amino acid residues is infered for the penicillinase precursor. Of these 34 amino acids precede the sequence of the secreted form of the enzyme. This peptide extension shows the features of a signal for secretion and also provides the hydrophobic anchor for the membrane bound form of the enzyme. PMID- 6269056 TI - Clustering of RNA polymerase B molecules in the 5' moiety of the adult beta globin gene of hen erythrocytes. AB - Nuclei were prepared from mature and immature hen erythrocytes and incubated for RNA synthesis in the absence or in the presence of Sarkosyl. The in vitro labelled synthesized RNA was hybridized to specific 5' and 3' fragments of the chicken adult beta-globin gene to investigate the possible presence of RNA polymerase molecules bound to this gene in the form of transcriptional complexes. Surprisingly, such RNA polymerase B molecules were found located preferentially in the 5' end moiety of the beta-globin genes of mature erythrocytes, although they are apparently evenly distributed along the beta-globin genes of immature polychromatic erythrocytes. The significance of these observations with respect to (1) preferential DNaseI sensitivity of "genes which have been transcribed" and (2) control of transcription in eukaryotic cells is discussed. PMID- 6269058 TI - The nucleotide sequence of rat alpha-tubulin: 3'-end characteristics, and evolutionary conservation. AB - The structure and sequence of rat alpha-tubulin cDNA clone is being described. The 3'-end of the coding region contains the codon for a C-terminal tyrosine, which was previously considered to be post-translationally added to the completed polypeptide chain. A close homology in the coding sequence is observed when a tubulin from rat and chick are compared, while the 3-non-translated region had diverged considerably. PMID- 6269057 TI - High sequence specificity of micrococcal nuclease. AB - The substrate specificity of micrococcal nuclease (EC 3.1.4.7.) has been studied. The enzyme recognises features of nucleotide composition, nucleotide sequence and tertiary structure of DNA. Kinetic analysis indicates that the rate of cleavage is 30 times greater at the 5' side of A or T than at G or C. Digestion of end labelled linear DNA molecules of known sequence revealed that only a limited number of sites are cut, generating a highly specific pattern of fragments. The frequency of cleavage at each site has been determined and it may reflect the poor base overlap in the 5' T-A 3' stack as well as the length of contiguous A and T residues. The same sequence preferences are found when DNA is assembled into nucleosomes. Deoxyribonuclease 1 (EC 3.1.4.5.) recognises many of the same sequence features. Micrococcal nuclease also mimics nuclease S1 selectively cleaving an inverted repeat in supercoiled pBR322. The value of micrococcal nuclease as a "non-specific" enzymatic probe for studying nucleosome phasing is questioned. PMID- 6269059 TI - DNA methyltransferases affecting the sequence 5'CCGG. AB - B. subtilis phage SPbeta and Moraxella sp. code for DNA methyltransferases which methylate both cytosines of the sequence 5'CCGG. Experiments using a B. subtilis strain whose DNA is sensitive to HpaII and resistant to MspI degradation, indicated that methylation of the outer C of this sequence provides protection against the restriction enzyme MspI. PMID- 6269060 TI - Cloning of multiple copies of immunoglobulin variable kappa genes in cosmid vectors. AB - The possibility of cloning large segments of DNA in cosmid vectors offers distinct advantages, in particular for the study of multigene families. Large size fragments of mouse embryo DNA were successfully cloned in the cosmid pHC 79. Twelve recombinants hybridizing specifically to an immunoglobulin kappa chain variable region probe were identified. In 9 of these recombinants, the size of the insert ranges from 30 to 43 kilobases. Factors affecting the cloning efficiency of a complex mammalian genome in cosmids were studied. The stability of these recombinant cosmids and the preparation of recombinant cosmid DNA are also discussed. PMID- 6269061 TI - Synthesis of oligodeoxyribonucleotides on silica gel support. AB - A rapid solid phase method of oligonucleotide synthesis based on monomeric protected nucleosides has been developed. PMID- 6269062 TI - The complete nucleotide sequence of an infectious clone of cauliflower mosaic virus by M13mp7 shotgun sequencing. AB - We have determined the complete primary structure (8031 base pairs) of an infectious clone of cauliflower mosaic virus strain CM1841. The sequence was obtained using the strategy of cloning shotgun restriction fragments in the sequencing vector M13mp7. Comparison of the CM1841 sequence with that published for another caMV strain (Strasbourg) reveals 4.4% changes, mostly nucleotide substitutions with a few small insertions and deletions. The six open reading frames in the sequence of the Strasbourg isolate are also present in CM1841. PMID- 6269063 TI - The nucleotide sequence of the cloned rpoD gene for the RNA polymerase sigma subunit from E coli K12. AB - We have determined the nucleotide sequence of the rpoD gene which codes for the sigma subunit of RNA polymerase from E. coli K12. The gene, which we formerly cloned as a HindIII restriction fragment in the transducing phage, charon 25, was recloned into several plasmids. We have determined a 2600 base pair DNA sequence which includes the entire structural gene for sigma. The resulting amino acid sequence agrees with previous information obtained about sigma including the amino acid composition, partial sequence data for the N-terminus, the highly acidic nature of the polypeptide, and the cleavage pattern at cysteines. The molecular weight of 70,263 daltons calculated for the 613 amino acid polypeptides is significantly lower than had been determined previously by SDS polyacrylamide gel analysis. PMID- 6269064 TI - Complete sequence of an IS element present in pSC101. AB - Recently a new insertion element (IS102)b ha been described in plasmid pSC101. We have determined its complete sequence: it consists of 1057 bp; 338 bp at one end are identical to those already determined for the kanamycin resistance transposon Tn903. It is not flanked by any direct repeat. Its coding capabilities are discussed, and compared to those of IS903. PMID- 6269065 TI - Sequence of a yeast DNA fragment containing a chromosomal replicator and a tRNA Glu 3 gene. AB - The sequence of a 1.9 kb Bam x Hind III fragment from yeast has been determined. This fragment is part of a yeast 6.7 kb Hind III segment cloned into pBR322 (pY20). The fragment carries a single gene for a glutamate tRNA which has no intron. According to genetic analyses [1] this fragment also contains a yeast chromosomal replicator. We have analyzed the sequence for potential open reading frames and for several structural features which are thought to be involved in the initiation of DNA replication. Hybridization studies have revealed that portions of this sequence are repeated within the yeast genome. PMID- 6269066 TI - Structural comparison of two yeast tRNA Glu 3 genes. AB - DNA sequences in a 1.7 kb Pst fragment from yeast have been determined. This fragment is part of a yeast 7.4 kb Hind III segment cloned ino pBR322 (pY 5). The fragment carries a single gene for a glutamate tRNA. The coding portion of this gene is identical in sequence to that of the tRNA Glu 3 gene from pY 20 [1]. The flanking regions differ in their sequences, but possible secondary structures within the 5'-flanking regions bear similar features. Sequence homologies between pY 5 and pY 20 were detected far outside the tRNA genes. More surprisingly, extended sequence homologies were seen between the flanking regions of the pY 20 tRNA Glu 3 gene and a tRNA Ser gene [2,3]. We have also checked the known tRNA genes for structural similarities. Hybridization studies indicate that portions of the Pst fragment are repeated within the yeast genome. PMID- 6269067 TI - Rapid and efficient cosmid cloning. AB - We present a procedure for cosmid cloning that allows rapid and efficient cloning of individual DNA fragments of between 32kb and 45kb. By appropriate treatment of the cloning vector, pJb8, we make left-hand and right-hand vector ends that are incapable of self-ligation but which accept dephosporylated insert DNA fragments. The inserted fragments are generated by partial digestion with MboI or Sau3A and are dephosphorylated to prevent ligation and insertion of non-contiguous fragments. The method eliminates the need to size the insert DNA fragments and prevents formation of clones containing short or multiple inserts. 1 microgram of target Drosophila DNA gives about 5 x 10(5) clones, with an average insert size of 38kb. We also describe a rapid and efficient method for preparing plasmid and cosmid DNA. PMID- 6269068 TI - Molecular cloning of the complete Epstein-Barr virus genome as a set of overlapping restriction endonuclease fragments. AB - A complete collection of fragments of Epstein-Barr virus DNA, obtained by cleavage with restriction endonuclease Eco RI, has been cloned. Fourteen different internal fragments of the virus genome, derived from linear virion DNA of the B95-8 strain, and sequences corresponding to the terminal regions of virion DNA, derived from intracellular circular EBV DNA isolated from 895-8 cells, were cloned. Sizes of fragments were determined by agarose gel electrophoresis and their sum leads to an estimated molecular weight of 110 x 10(6) for virion DNA. Large Eco RI DNA fragments of special interest were also cloned in cosmids using another source of EBV DNA, that is, to circular viral DNA derived from Raji cells. In order to provide a set of overlapping sequences, all the 29 internal Bam HI fragments of B95-8 virion DNA were cloned in pBR322. The map location within the viral genome of each cloned DNA fragment was identified by hybridizing to blots of virion DNA cleaved with several different restriction endonucleases. PMID- 6269069 TI - Shotgun DNA sequencing using cloned DNase I-generated fragments. AB - A method for DNA sequencing has been developed that utilises libraries of cloned randomly-fragmented DNA. The DNA to be sequenced is first subjected to limit attach by a non-specific endonuclease (DNase I in the presence of Mn++), fractionated by size and cloned in a single-stranded phage vector. Clones are then picked at random and used to provide a template for sequencing by the dideoxynucleotide chain termination method. This technique was used to sequence completely a 4257 bp EcoRI fragment of bovine mitochondrial DNA. The cloned fragments were evenly distributed with respect to the EcoRI fragment, and completion of the entire sequence required the construction of only a single library. In general, once a clone library has been prepared, the speed of this approach (greater than 1000 nucleotides of randomly selected sequence per day) is limited mainly by the rate at which the data can be processed. Because the clones are selected randomly, however, the average amount of new sequence information per clone is substantially diminished as the sequence near completion. PMID- 6269070 TI - Circular dichroism spectra of twelve short DNA restriction fragments of known sequence: a comparison of measured and calculated spectra. AB - The CD spectra of twelve DNA restriction fragments ranging in size from 12 to 360 base pairs are reported. Since the sequences of these fragments are known, it is possible to calculate their CD spectra from a set of nearest neighbor contributions derived from a combination of synthetic polydeoxyribonucleotides. While the calculations lead to good agreement in the negative band at approximately 245 nm, they generally reproduce the positive band at approximately 270 nm only poorly. The experimentally observed positive band consists of two peaks centered around 270 and 285 nm. The comparison of calculated and measured spectra reveals that end effects lead to increased disagreement for fragments smaller than approximately 40 base pairs. The disagreement between calculated and measured spectra can be partially attributed to the fraction of next nearest neighbors in the DNAs, which are also in the spectral components. Thus, the sequence specific CD contributions in the long wavelength region of the spectra extend at least to next nearest neighbor nucleotides and may extend beyond. PMID- 6269071 TI - A gel electrophoresis method for quantifying the binding of proteins to specific DNA regions: application to components of the Escherichia coli lactose operon regulatory system. AB - The use of gel electrophoresis for quantitative studies of DNA-protein interactions is described. This rapid and simple technique involves separation of free DNA from DNA-protein complexes based on differences in their electrophoretic mobilities in polyacrylamide gels. Under favorable conditions both unbound DNA and DNA associated with protein can be quantified. This gel method is applied to the study of the E. coli lactose operon regulatory system. At ionic strengths in the physiological range, the catabolite activator protein (CAP) is shown to form a long-lived complex with the wild type lac promotor, but not with a CAP insensitive mutant. Formation of a stable "open" or "melted-in" complex of RNA polymerase with the wild type promoter requires the participation of CAP and cyclic AMP. Further, it is demonstrated that even when pre-formed in the presence of CAP-cAMP, the polymerase-promoter open complex becomes unstable if CAP is then selectively removed. PMID- 6269072 TI - Vertebrate histone genes: nucleotide sequence of a chicken H2A gene and regulatory flanking sequences. AB - The DNA sequence of a chicken genomal fragment containing a histone H2A gene has been determined. It contains extensive 5' and 3' flanking regions and encodes a protein identical in sequence to the histone H2A protein isolated from chicken erythrocytes. In the 5' flanking region, a possible "TATA box" and three possible "cap sites" can be recognised upstream from the initiation codon. To the 5' side of the "TATA box" is found an unusual sequence of 21 A's interrupted by a central G residue. It occupies the same relative position as the P. miliaris H2A gene specific 5' dyad symmetry sequence and the "CCAAT box" seen in other eukaryotic polymerase II genes but is clearly different from both. A significant feature of the 3' non-coding region is the presence of a 23 base-pair sequence that is nearly identical to a conserved region found in sea urchin histone genes. The coding region is extremely GC rich, with strong selection for these bases in the third position of codons. Not a single coding triplet ends in U. No intervening sequences were found in this gene. PMID- 6269073 TI - Rapid turnover of the histone-ubiquitin conjugate, protein A24. AB - The specific activity of protein A24 was found to exceed that of the core histones by 2-3 fold following a brief labeling period. Accordingly, the A24 protein was found to be unstable, with a decay half-life of 90 minutes. When decay of the ubiquitin moiety was measured, it was found to turn over more extensively than the H2A moiety. PMID- 6269074 TI - Reaction kinetics of some important site-specific endonucleases. AB - Reaction kinetics of the site-specific endonucleases BamHI, BgIII, C1aI, EcoRI, HpaII, PstI, SaII, SmaI, and XorII were investigated employing some frequently used substrates. Six of these enzymes could be analyzed under steady-state conditions. Kinetic data were obtained from progress curves applying an integrated Michaelis-Menten equation. KM ranged from 4 x 10(-9) M to 4 x 10(-11) M. Activities also spanned two orders of magnitude. In the case of C1aI the analysis of the pre-steady-state kinetics ("burst reaction") allowed the assessment of several rate constants. The rate-limiting step is the very slow dissociation of the enzyme-product complex (0.22 min(-1)). This complex is formed from the enzyme-bound nicked intermediate at a rate of 1.7 min(-1). The introduction of the first cut is again faster by a factor of about 6. SmaI and XorII resembled C1aI in their kinetics. The burst reaction can be used for the easy and unambiguous determination of molar concentrations of site-specific endonucleases in any preparation, which is free of non-specific DNases. PMID- 6269075 TI - Organization of ribosomal RNA gene repeats of the mouse. AB - The organization of the ribosomal RNA (rRNA) genes of the mouse was determined by Southern blot hybridization using cloned rDNA fragments as probes, which could encompass the entire spacer region between two rRNA gene regions. The rRNA genes are organized into tandem repeats of nearly uniform length of about 44 kb. The heterogeneity detected in the nontranscribed spacer appears to be caused by its sequence rather than its length difference. At least three kinds of repetitive sequences are present in the non-transcribed spacer region; two of them are located 13 kb upstream from the 5'-end of 18S RNA gene and the other located 1 to 4 kb downstream from the 3'-end of 28S RNA gene. PMID- 6269076 TI - Satellite DNA relationships in man and the primates. AB - We have investigated the genomes of a series of primates to identify the presence of sequences related to human satellite DNAs I, II and III by restriction enzyme digestion and hybridisation with probes of these satellite DNAs. Where we have found such related sequences we have examined the extent to which they have diverged by measuring the stability of the hybrids. DNA satellite III is the oldest sequence being common to species which have diverged some 24 million years ago. In contrast DNA satellites I and II are of much more recent origin. Our results permit us to draw conclusions about the way these sequences have evolved, and how the evolution of repeated DNA sequences may be related to the evolution of the primate lineage. PMID- 6269077 TI - The structure of the gene for the large subunit of ribulose 1,5-bisphosphate carboxylase from spinach chloroplast DNA. AB - A cloned fragment of spinach chloroplast DNA carrying the gene for the large subunit of ribulose bisphosphate (RuBP) carboxylase has been analysed by electron microscopy of R-loops, by hybridization to Northern blots of chloroplast RNA, by S1 nuclease mapping and by DNA sequencing. The transcribed region of the gene is 1690 +/- 3 nucleotides long and co-linear with its mRNA. It comprises a 178-179 bp 5' untranslated sequence, a 1425 bp coding region and an 85-88 bp 3' untranslated region. The deduced sequence of the 475 amino acids of the spinach large subunit protein shows 10% divergence from that of the maize large subunit protein (1). The nucleotide sequence divergence between spinach and maize over the same coding region is 16% but in the transcribed flanking regions it is 35%. Features of the spinach chloroplast gene which resemble those of bacterial genes include a 5-base Shine-Dalgarno sequence complementary to a sequence near the 3' end of chloroplast and bacterial 16S rRNA, a promoter region partially homologous to a consensus sequence of bacterial promoters, and a transcription termination region capable of forming a typical stem and loop structure. PMID- 6269078 TI - Isolation and characterization of genomic clones covering the chicken vitellogenin gene. AB - A series of overlapping recombinant clones, which cover the vitellogenin gene, has been isolated from a phage-lambda linked chicken gene library. The DNA of the overlapping clones spans 28 kb of contiguous DNA sequences in the chicken genome. Electron microscopic analysis of hybrids between vitellogenin mRNA and the genomic clones indicates that the chicken vitellogenin gene has a length of approximately 22 kb, about 3.8 times the size of the mRNA. The mRNA sequence is interrupted by at least 33 intervening sequences (introns). Comparison with the vitellogenin gene A2 from Xenopus laevis (Wahli et al., 1980, Cell 20: 107-117) indicates conservation of the number and length of the exons during evolution. Heteroduplex analysis reveals a short stretch of sequence homology between the genes from chicken and frog. PMID- 6269079 TI - Induction of premature termination of transcription of the mouse beta-globin gene by 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB). AB - Hybridization of pulse-labeled RNA from DRB-treated Friend cells to mouse beta globin cDNA revealed that the appearance of beta-globin mRNA in the cytoplasm was inhibited by greater than 87%. To examine the effect of DRB (125 microM) on HnRNA synthesis, nuclear RNA was electrophoresed in methyl mercuric hydroxide gels, transferred to nitrocellulose, and hybridized with beta-globin specific probes. Full-length nuclear transcripts, while present in untreated cells, were not detected in DRB-treated cells. Using restriction enzymes, the cloned beta-globin gene was divided into fragments proceeding from the 5' gene region to the 3' gene region. RNA labeled in vitro by transcription in nuclei isolated from DRB-treated cells hybridized only to the promoter proximal DNA fragment. Transcripts hybridizing to fragments from both the 5' and 3' regions of the gene were produced in nuclei from untreated cells. Together these results indicate that DRB causes premature termination of transcription within the beta-globin gene. PMID- 6269081 TI - A promoter of pBR322 activated by cAMP receptor protein. AB - We have demonstrated in vitro the existence on the plasmid pBR322 of a promoter signal that is strictly dependent on cAMP and its receptor protein CRP. Transcription initiates with pppG at nucleotide 2270 and proceeds counterclockwise on the standard pBR322 map. DNase protection studies show that CRP selectively binds to the -35 region of the promoter. This region exhibits strong structural homologies to the binding sites of other CRP-dependent promoters. PMID- 6269080 TI - Construction and characterization of recombinant plasmid DNAs containing sequences of the origin of bacteriophage phi X174 DNA replication. AB - The synthetic DNA fragment (formula, see text) (corresponding to nucleotides 4299 4314 of the phi X DNA sequence) was cloned into either the AmpR gene or the KmR gene of plasmid pACYC 177. The DNA sequence of the KmR gene around the insertion site was determined by nucleotide sequence analysis of the pACYC 177 FnudII restriction DNA fragment N6 (345 b.p.). Of five selected plasmid DNAs, which contained inserted DNA sequences in the antibiotic resistance genes, the nucleotide sequences at and around these insertions were determined. Two recombinant plasmids (pFH 704 and pFH 614) contain the hexadecamer sequence in tandem (tail-to-tail and tail-to-head). In the recombinant plasmids pFH 812, pFH 903 and pFH 807 the DNA sequence homology with the phi X origin region was 14 (No. 4300-4313), 16 (No. 4299-4314) and 20 nucleotides (No. 4299-4318), respectively. None of the supercoiled recombinant plasmid DNAs is nicked upon incubation with phi X gene A protein. Moreover, the recombinant plasmid RFI DNAs cannot act as substitutes for phi X RFI DNA in the in vitro (+) strand synthesizing system. It has been shown earlier that single-stranded DNA, which contains the decamer sequence CAACTTGATA is efficiently nicked by the phi X gene A protein. The present results indicate that for nicking of double-stranded supercoiled DNA nucleotide sequence homology with the phi X origin region of more than 20 nucleotides is required. These results suggest a model for initiation of phi X RF DNA replication, which involves the presence of the recognition sequence CAACTTGATA of the phi X gene A protein as well as a second specific nucleotide sequence which is required for the binding of the phi X gene A protein. This binding causes local unwinding of the DNA double helix and exposure of the recognition sequence in a single-stranded form, which then can be nicked by phi X gene A protein. PMID- 6269083 TI - Mobile dispersed genetic element MDG1 of Drosophila melanogaster: nucleotide sequence of long terminal repeats. AB - Long terminal repeats (LTRs) of two members of mdg1 family were sequenced. In the both cases, they are represented by perfect direct repeats 442 and 444 bp in length. Sixteen nucleotides in the LTRs of two different mdg1 elements are different. Each LTR contains slightly mismatched 16-nucleotide inverted repeats located at the ends of the LTR. Six base pairs closest to the termini of LTR form perfect inverted repeats. On the gene-distal sides of LTRs, short 4-nucleotide direct repeats are located, probably representing the duplication of a target DNA sequence arising from insertion of mdg. They are different in the two cases analyzed. Just as the other analyzed eukaryotic transposable elements, mdg1 starts with TGT and ends with ACA. Within the both strands of LTR, the sequences similar to Hogness box (a putative signal for RNA initiation, or a selector) and AATAAA blocks (putative polyadenylation signals) are present. The LTR of mdg1 contains many short direct and inverted repetitive sequences. These include a 10 nucleotide sequence forming a perfect direct repeat with the first ten nucleotides of the LTR. A region of LTR about 70 bp long is represented by simple repetitive sequences (TAT). PMID- 6269082 TI - The DNA sequence of the promoter-attenuator of the ilvGEDA operon of Salmonella typhimurium. AB - The isolation of a lambda gt . ilvGEDA . S.t. hybrid transducing phage has permitted the characterization of the promoter-attenuator region of the ilvGEDA operon of Salmonella typhimurium. In vitro transcription and Southern hybridization indicate that the promoter-attenuator resides on a 400 nucleotide Rsa I restriction fragment. DNA sequence analysis shows only seven base pair differences exist between the DNA sequence of the ilvGEDA promoter-attenuator of S. typhimurium and that previously published for Escherichia coli K12. PMID- 6269084 TI - Transient cleavage kinetics of the Eco RI restriction endonuclease measured in a pulsed quench-flow apparatus: enzyme concentration-dependent activity change. AB - We report measurements of the cleavage rate of pBR 322 plasmid DNA by the restriction endonuclease Eco RI as a function of enzyme and DNA concentration. The reaction, which at high excess of enzyme over DNA occurs between 0.2 and 5 seconds, was studied by the means of a microprocessor controlled pulsed quench flow apparatus. Enzyme concentrations were between 1 and 100 nM with DNA concentrations being 3 to 6 nM (specific Eco RI sites). The catalytic constants for cleavage of the first and second phosphodiester bonds as measured at high enzyme concentration both have the same value of 0.35 sec-1 and 21 degrees C. At enzyme concentrations comparable to or less than DNA concentration, the rate of the first cleavage is proportional to enzyme concentration, while the second step is independent of concentration. At approx. 10 nM Eco RI endonuclease concentration, a rate increase shows up in both the first and the second cleavage. We suggest that this increase is due to the tetramerization reported by Modrich & Zabel1, which occurs in this concentration range. PMID- 6269085 TI - DNA organisation in the chicken lysozyme gene region. AB - DNA sequences surrounding the lysozyme gene of the chicken have been cloned in several recombinants which define a region of 40 Kb. We have detected no other gene with a sequence related to that of the lysozyme gene, nor any gene expressed in the oviduct in these recombinants. This situation contrasts with that of the ovalbumin gene, in the vicinity of which lie two other genes of related structure expressed in the oviduct under hormonal control. The lysozyme gene region, however contains a complex array of repeated sequences, which have been resolved into at least five classes. An inverted repeat overlaps the lysozyme gene itself. PMID- 6269086 TI - DNA gyrase: affinity chromatography on novobiocin-Sepharose and catalytic properties. AB - Novobiocin-Sepharose was prepared by coupling of novobiocin to Epoxy-activated Sepharose 6B and used as an affinity adsorbent. Four novobiocin-binding proteins were isolated from crude extracts of Escherichia coli with molecular weights of 105, 92, 85 and 40 kdal. The two larger proteins were identified as the A subunit (gyrA protein) and the B subunit (gyrB protein) of DNA gyrase topoisomerase II). By this method the two gyrase components can be easily separated and purified in high yield. Although both proteins are involved in the ATP-dependent supercoiling of relaxed plasmid DNA, only the gyrB protein is required for catalyzing the cleavage of ATP. The gyrB protein ATPase activity is competitively inhibited by novobiocin and related coumarin antibiotics. ATP hydrolysis is unaffected by the addition of either gyrA protein or DNA but stimulated in the presence of both. PMID- 6269087 TI - The integrated forms of the S1 and S2 DNA elements of maize male sterile mitochondrial DNA are flanked by a large repeated sequence. AB - The mitochondrial DNA of maize was cloned using the cosmid, Homer I. Recombinants carrying sequences homologous to the S1 and S2 DNA elements of male sterile maize have been analysed. Restriction endonuclease maps for Sac II, Sma I and Bam HI have been constructed. The S1 and S2 sequences are single copy sequences occurring at unique sites; each is flanked by a 26 kb repeated sequence. The repeated sequence has been shown not to contain the mitochondrial ribosomal RNA genes. PMID- 6269088 TI - Cloning and mapping of the chloroplast DNA sequences for two messenger RNAs from mustard (Sinapis alba L.). AB - Restriction fragments of chloroplast (cp)DNA from mustard leaves were cloned in E. coli using pBR 322 as the vehicle. Cloned fragments containing the structural sequences for two polypeptides of 56,000 and 35,000 daltons were selected by a mRNA hybridization-translation procedure. The cloned mustard genes are structurally related to chloroplast genes from maize. They hybridize to the maize mRNAs for the large subunit of ribulosebisphosphate carboxylase and for the 34,500 dalton precursor to a membrane protein. The coding sequence on mustard cpDNA for the 56,000 dalton polypeptide is colinear with a 1,500 base pair transcript, and the sequence for the 35,000 dalton polypeptide is colinear with a 1,220 base pair transcript. PMID- 6269089 TI - Specific and reversible inhibition of the blunt end joining activity of the T4 DNA ligase. AB - Specific, complete and reversible inhibition of the joining of blunt ended DNA duplexes catalyzed by the T4 DNA ligase can be obtained by using ATP, the enzyme cofactor, at concentrations of 5 mM and higher. On cohesive DNA ends, 5 mM ATP, which completely inhibits blunt end ligation, brings about only a limited (8%) reduction in the level of joining obtainable under optimal ATP concentration (0,5 mM or lower). A similar but less drastic uncoupling of the two kinds of joining can be achieved at lower ATP concentration (2,5 mM) using 1 mM Mg++. The joining of DNA blunt ends can also be inhibited almost completely by 10 mM spermidine, without noticeable effect on the joining of cohesive termini. PMID- 6269090 TI - Two types of triplicated alpha-globin loci in humans. AB - DNA from healthy Malaysian newborns was studied on gene maps after digestion with different restriction endonucleases. Of 65 newborns, two were found to be carriers of two different variants of triplicated alpha-globin loci. In variant no. 1, found in an Malay, the three alpha-globin genes are in an elongated DNA fragment on digestion with Eco RI and Bam HI. The third alpha-globin gene was found in a additional 3.7-kb fragment on digestion with Hpa I, Bgl II and Hind III. In variant no. 2, a new type of triplicated alpha-globin loci, found in a Chinese, the three alpha-globin genes reside in an elongated DNA fragment longer than that of variant no. 1 on digestion with Eco RI and Bam HI. The third alpha globin gene was found in an additional 4.2-kb fragment on digestion with Hpa I and Hind III. Digestion of this variant DNA with Bg1 II produced an abnormal 16.7 kb fragment in addition to the normal 7.0-kb Bgl-II fragment. The locations of the restriction sites in the two types of triplicated alpha-globin loci are compatible with a mechanism of unequal crossing over following two different modes of misalignment. PMID- 6269091 TI - Human growth hormone DNA sequence and mRNA structure: possible alternative splicing. AB - We have determined the complete sequence of the human growth hormone (hGH) gene and the position of the mature 5' end of the hGH mRNA within the sequence. Comparison of this sequence with that of a cloned hGH cDNA shows that the gene is interrupted by four intervening sequences. S1 mapping shows that one of these intervening sequences has two different 3' splice sites. These alternate splicing pathways generate hGH peptides of different sizes which are found in normal pituitaries. Comparison of sequences near the 5' end of the hGH mRNA with a similar region of the alpha subunit of the human glycoprotein hormones reveals an unexpected region of homology between these otherwise unrelated peptide hormones. PMID- 6269092 TI - Isolation and characterization of the complete chicken beta-globin gene region: frequent deletion of the adult beta-globin genes in lambda. AB - A library of bacteriophage lambda clones containing chicken chromosomal DNA was screened, using the adult beta-globin cDNA plasmid pHb 1001 as a probe. Sixteen overlapping clones were isolated containing 35 kilobase pairs (kbp) of chicken DNA. Characterization of these clones revealed four beta-like globin genes, some genomically repeated sequences, but no pseudo-genes. The four beta-like genes have an average intergenic distance of less than half of that found for the mammalian beta-like globin gene clusters so far characterized. The overall features of the map were confirmed by genomic Southern analysis. Frequent deletions were shown to occur between the various beta-like globin genes during phage propagation. The presumptive hatching gene in particular was always associated with abnormal lambda clones although we were able to find one such clone that did contain a normal copy of the hatching gene itself. Probably such deletions explain the failure to recover this gene in previous attempts. PMID- 6269093 TI - Replication of SV40 chromatin in extracts from eggs of Xenopus laevis. AB - Simian virus 40 (SV40) nucleoprotein complexes were prepared from lytically infected cells and used as primer-templates for DNA replication in protein extracts from Xenopus eggs. We found that nucleoprotein containing replicating SV40 DNA served as primer-template while nucleoprotein with nonreplicating SV40 DNA was ineffective. In vitro DNA synthesis begins with short DNA fragments ("Okazaki fragments") which are, in later steps, joined to give unit length SV40 DNA strands, suggesting that in vivo initiated rounds of replication are completed in vitro in the Xenopus system. This conclusion is supported by a restriction enzyme analysis showing that in vitro DNA synthesis occurs in fragments distal to the SV40 origin of replication. Our studies indicate that SV40 DNA replication in Xenopus extracts can be used an an experimental system to study the biochemistry of replicative DNA chain elongation in vitro. PMID- 6269094 TI - Effects of obstruction on single-kidney function: clinical and experimental results with 131I-hippurate and 99mTc-DMSA. AB - In 35 patients, renography with 131I-o-hippurate (OIH) and static renal imaging with 99mTc-dimercaptosuccinic acid (DMSA) were used to measure differential renal function (DRF). The results were compared. Depth correction was applied in both methods. In non-obstructed kidneys (19 patients), both methods revealed nearly identical kidney function (r = 0.98). For completely obstructed kidneys (16 patients), OIH gave a significantly better DRF (14 ml/min) than DMSA. This small difference was of no clinical value. Because DMSA is reported to give unreliable results in unilateral obstructed kidneys, the right ureter was ligated in 8 dogs for 10 days and DRF was measured before and after opening an ureteral fistula. The difference in DRF was about 1% and could be accounted for by the amount of urinary radioactivity collected from the pelvic system after the ligature had been opened. Although DMSA appears to give reliable values in determining DRF, even in obstructed kidneys, OIH is preferred since total clearance values and postrenal urinary dynamics can be determined simultaneously. PMID- 6269095 TI - [Results of treatment of small-cell bronchial cancer with chemotherapy combined with radioisotope teletherapy]. PMID- 6269096 TI - [Results of treatment of undifferentiated lung cancer with vincristine combined with cyclophosphamide]. PMID- 6269097 TI - [Early results of chemotherapy combined with Co-60 radiotherapy of undifferentiated lung cancer]. PMID- 6269098 TI - [Case of hormonally inactive giant pancreatic insulinoma]. PMID- 6269099 TI - [Radiological aspects of periradicular cysts and meningeal diverticula in the lumbosacral segment (author's transl)]. PMID- 6269100 TI - Nutrition, brain function and behavior. AB - Current food intake has been shown to directly affect neurotransmission, with resultant modification of behavior. The role of vitamin co-factors in brain function is discussed, with emphasis on changes in mood and neurological function with deficiency. The use of megadoses of vitamins for the treatment of psychiatric diseases has little scientific support at this time. Current research also does not substantiate the Feingold thesis of improvement in childhood hyperkinesis when an additive-free diet is consumed. The effects of medications used to moderate mood are related to changes in nutrient intake that in turn alters weight status. In addition, the effect of certain nutrients modifying the dose response to mood altering drugs has been discussed. Finally evidence for mood state directly affecting the capacity of the body to utilize nutrients is presented. PMID- 6269101 TI - [Biochemical analysis of a supernatant of a leukemic cell culture]. PMID- 6269102 TI - [Osteogenesis imperfecta. Review of therapeutic methods]. PMID- 6269103 TI - Pathogenesis of thymic lymphomas in C57BL mice. PMID- 6269104 TI - Paget's disease of the vulva with underlying apocrine adenocarcinoma and local lymph node invasion. AB - A case of Paget's disease of the vulva with an underlying apocrine adenocarcinoma and local lymph node invasion is reported in a female aged 70. Subjective symptoms of pruritus, burning and pain were associated with typical, but unspecific clinical findings of an erythematous, indistinctly limited, weeping lesion of palm-size with small superficial erosions. Near the right labium majus a solid measuring 2.5 X 1.5 cm in diameter was palpable. The diagnosis was established by microscopic examination of biopsy material, showing intraepidermally the typical Paget's disease with a subjacent, highly differentiated apocrine adenocarcinoma of the sweat glands combined with inguinal lymph node invasion. Other epidermal malignancies were excluded by histochemical reactions. For therapy, telecobalt irradiation combined with high energy electron was applied. PMID- 6269105 TI - The influence of psychotropic drugs on the phosphodiesterase activity in the rat brain meninges. AB - Phosphodiesterase (PDE) is present in brain meninges. Its activity is higher in the pia than in the dura mater. Phenothiazine neuroleptics: fluphenazine, trifluoroperazine, thioproperazine, chloropromazine and thioridazine at concentration 10(-5)--10(-4) M in vitro inhibit the PDE activity in the pia and dura mater. Most potent in this respect were fluphenazine and trifluoroperazine. Much less pronounced inhibition of PDE activity in brain meninges was found after in vitro administration of tricyclic antidepressant: nortriptyline, chlorimipramine, protriptyline, desipramine and imipramine in concentrations 10( 4)--10(-3) M. Administered in vivo in a dose of 0.1 mg or 5 mg/kg ip fluphenazine inhibited the hydrolysis of 32P-cAMP injected into subarachnoid space. The results indicate that PDE present in the rat brain meninges may control the cAMP level in the cerebrospinal fluid. Treatment with phenothiazine neuroleptics which inhibit the PDE activity in meninges may significantly depress the hydrolysis of cAMP in the cerebrospinal fluid. PMID- 6269106 TI - Prostatic crystalloids: association with adenocarcinoma. AB - With review of 393 consecutive cases of previously documented prostatic adenocarcinoma, the coexistence of intraglandular crystalloids was confirmed. The various morphologic appearances of these structures are described. Unequivocal crystalloids were identified in 10% of cases. They were most often located in the acini of malignant glands but occasionally were observed in benign glands adjacent to carcinoma. Of available clinical and demographic parameters analyzed, several unexplained statistical relationships were observed, but none of the variables could be used to characterize the patients with crystalloids. This paper suggests that these structures may be useful in the diagnosis of prostatic adenocarcinoma when only inadequate or equivocal biopsy material is available. PMID- 6269107 TI - Penicillanic acid derivatives in the canine prostate. AB - Distribution of ampicillin, amoxicillin, bacampicillin, mecillinam, pivmecillinam, carbenicillin, indanyl sodium was studied in the canine prostate, prostatic interstitial fluid, and prostatic secretion. All seven antibiotics were found in higher concentrations in the prostatic interstitial fluid than in the prostatic secretion. As expected for weak acids, drug concentrations in these fluids were always lower than the simultaneous serum concentrations. Tissue penetration was enhanced for the penicillin ester, pivmecillinam, as shown by its prostatic secretion/serum and tissue/serum ratios, which were higher than those of the other antibiotics, including the esters, bacampicillin, and carbenicillin indanyl sodium. This results may be due to pivmecillinam's long hydrolysis half life. The concentrations for these penicillanic acid derivatives in prostatic interstitial fluid were above the minimal inhibitory concentrations for most of the commonly encountered gram-negative bacteria encountered in prostatitis. Therefore, these antibiotics should be effective in the treatment of bacterial prostatitis caused by susceptible organisms. Carbenicillin and carbenicillin indanyl sodium had the highest prostatic interstitial fluid/serum ratios of the compounds tested, and theoretically, therefore, they should be the most effective in the treatment of prostatitis. However, clinical trials should be carried out to confirm this. PMID- 6269109 TI - Acute viral hepatitis. PMID- 6269108 TI - Obstructive sodium-losing nephropathy--a case report and review. AB - The third case in the literature of sodium-losing renal disease due to obstruction is presented. The experimental evidence and limited clinical experience is reviewed which suggests that the sodium loss is due to an inappropriate response in the adaptive processes that are initiated by the loss of functioning nephrons. The immediate treatment is by replacement of sodium but in the long term the condition may be reversed by very cautious reduction in sodium intake. Definitive treatment may be indicated where obstruction is the cause and consequently this should be sought in all cases of salt-losing renal disease. PMID- 6269110 TI - Evidence that adenovirus type 2 can infect human placenta in vitro. PMID- 6269111 TI - [Trypsin immobilization in silica gel]. AB - Trypsin immobilization in an inorganic polymer, i.e. silica gel, was investigated. Properties of the immobilized enzyme were examined. It was found that the enzyme retained its activity, depending on the gel genesis and dehydration of the carrier. The effect of stabilizing supplements on the enzyme activity was studied. The enzyme immobilization was accompanied by an increase in its thermostability. PMID- 6269112 TI - Ventromedial hypothalamic lesions reduce the number of NA+, K+-ATPase enzyme units in skeletal muscle of weanling rats. PMID- 6269113 TI - Elevated arterial pressure, vascular wall "waterlogging," and impaired cardiac growth in rats chronically receiving digoxin. PMID- 6269114 TI - beta Receptor mediated transfer in potassium loaded nephrectomized dogs. PMID- 6269115 TI - Rat hepatocyte-mediated mutagenesis of human cells by carcinogenic polycyclic aromatic hydrocarbons but not organochlorine pesticides. PMID- 6269116 TI - Effect of murine cytomegalovirus on implantation stage mouse embryos. PMID- 6269117 TI - Characterization of sarcoma-positive, leukemia-negative (S+L-) human cells induced by the feline leukemia virus pseudotype of Moloney sarcoma virus. PMID- 6269118 TI - Chronomorphology of mammalian tissues. PMID- 6269119 TI - Influence of bacterial endotoxins on neutrophilic leukocytes: lack of a correlation between in vivo and in vitro responses. PMID- 6269120 TI - Actions of endotoxins on excitation-secretion coupling at the neural membrane. PMID- 6269121 TI - Brain benzodiazepine receptor changes in the isolated aggressive mouse. PMID- 6269122 TI - Periodate oxidimetric determination of nadolol. PMID- 6269123 TI - Alteration by vanadate of contractility in vascular and intestinal smooth muscle preparations. AB - Intestinal muscle was more sensitive than vascular muscle to vanadate. Vanadate caused a biphasic response in intestinal muscle; inhibition of spontaneous contractile activity was followed by a return of phasic contractions and a sustained increase in baseline tension. Then inhibitory response appeared to be due to vanadate-induced release of an inhibitory transmitter from intramural nerve endings. The excitatory response appeared to be due to the action of vanadate at an intracellular site, possibly by inhibition of a Ca-ATPase that controls intracellular Ca2+ levels. Vanadate did not alter intracellular Na+ and K+ levels in isolated longitudinal muscle. Thus, inhibition of intestinal muscle NaK-ATPase cannot account for the alterations in contractility. PMID- 6269124 TI - Breakdown and fate of ACTH and MSH. PMID- 6269125 TI - Neuropeptides and brain cAMP and phosphoproteins. PMID- 6269126 TI - Host cell reactivation and UV-enhanced reactivation in synchronized mammalian cells. PMID- 6269127 TI - Solute asymmetric energy of transfer (channel partition) model and the cause of cancer. AB - A model for all solute transport is outlined in which flux rates and intracellular accumulation depend on partition barriers to the solute at the inner and outer channel openings of the intramembrane particles. Carcinogens would bind at and enlarge the outer channel opening, allowing increased influx of Na and Ca and thus triggering cellular replication. PMID- 6269128 TI - Physical characterization of a plasmid (pTT1) isolated from Thermus thermophilus. PMID- 6269129 TI - The use of transposons to introduce well-defined deletions in plasmids: possibilities for in vivo cloning. PMID- 6269130 TI - The insertion sequence IS21 of R68.45 and the molecular basis for mobilization of the bacterial chromosome. PMID- 6269131 TI - Origin and mode of replication of plasmids pE194 and pUB110. PMID- 6269132 TI - Specific pattern of instability of Escherichia coli HisG gene cloned in Bacillus subtilis via the Staphylococcus aureus plasmid pCS194. PMID- 6269133 TI - Lacrimal gland adenoid cystic carcinoma: intracranial and extracranial en bloc resection. AB - Adenoid cystic carcinoma of the lacrimal gland is a rare tumor, although it is the malignancy most frequently arising in the gland. Treatment has been unsuccessful generally, with a 15-year survival of less than 20 percent. Our experience with this tumor in a 61-year-old woman has led to a proposal for therapeutic management based on awareness of the lesion's natural history, an understanding of regional anatomy, and familiarity with therapies reported in the literature. The feasibility of adequate tumor ablation is determined from preoperative evaluation, including CT scan, initial exploratory craniotomy, and frozen-section examination of the cranial nerves transversing the orbit. Once resectability is confirmed, "curative" intracranial and extracranial en bloc resection is performed, including the tumor, the lacrimal gland, and all contiguous structures. The defect is immediately resurfaced with and "ice cream cone" forehead flap in anticipation of adjuvant radiotherapy. An orbital prosthesis is fitted as soon as the radiation reaction subsides, and a postablative CT scan is obtained as the baseline for follow-up. It remains to be seen whether this application of the technology of CT scanning and the techniques of craniofacial surgery will improve the prognosis for adenoid cystic carcinoma arising in the lacrimal gland. PMID- 6269134 TI - Dermal cylindroma: surgical approach. PMID- 6269135 TI - The use of gamma-linolenic acid and linoleic acid to differentiate between temporal lobe epilepsy and schizophrenia. AB - Three long-stay, hospitalised schizophrenics who had failed to respond adequately to conventional drug therapy were treated with gamma-linolenic acid and linoleic acid in the form of evening primrose oil. They became substantially worse and electroencephalographic features of temporal lobe epilepsy became apparent. In all three the clinical state dramatically improved when carbamazepine, the conventional therapy for temporal lobe epilepsy was introduced. It can be extremely difficult to distinguish on clinical grounds between schizophrenia and temporal lobe epilepsy, and electroencephalographic studies do not always reveal an abnormality in the temporal lobe syndrome, unless additional procedure such as sphenoidal electroencephalography is undertaken. A trial of therapy with gamma linolenic acid may prove of considerable value in distinguishing between these two states, so allowing specific therapy to be introduced. PMID- 6269136 TI - Indomethacin causes a simultaneous decrease of both prolactin binding and fluidity of mouse liver membranes. AB - Indomethacin suppressed the numbers of prolactin receptors detectable in the liver membranes of both male and female C3H mice. This occurred in a dose dependent fashion with 7.5 mug/gm body weight injected every 4 hours exerting a maximal effect within 20 hours. While injection of 50 mug prolactin every 4 hr increased the number of prolactin receptors in control animals it could not in the indomethacin-treated animals. Membrane fluidity was estimated by fluorescence polarization techniques using the lipid probe 1, 6-diphenylhexatriene. Indomethacin caused a decrease in membrane fluidity, whereas, exogenous prolactin increased the fluidity of the recipients' liver membranes but again could not overcome these suppressive effects of indomethacin. The data suggest that prolactin induces its own membrane-associated receptor by means of the prostaglandin cascade, perhaps by altering the fluidity of the supporting lipid bilayer. PMID- 6269137 TI - Influence of cardiac rhythm disturbances and antiarrhythmic drugs on the efflux of PGE, PGF2 alpha, cyclic AMP, and cyclic GMP in canine coronary sinus blood. AB - In anaesthetized open-chest dogs, cardiac arrhythmias (CA) were induced by cumulative intravenous doses of aconitine or ouabain. Aconitine in a dose which did not induce CA had no influence on the PGE and PGF2 alpha effluxes into coronary sinus blood (CSB), whereas the PGE efflux into CSB increased after a subtoxic dose of ouabain. However, both PGE and PGF2 alpha effluxes were increased, when CA had developed. During aconitine induced CA, the PGE efflux was 6.5-fold and that of PGF2 alpha had increased by 80%. During ouabain induced CA, the effluxes of both PGs were about 3-fold. Propranolol and lidocaine decreased the PGF2 alpha efflux into CSB by about 50% and the PGE efflux was doubled after lidocaine and decreased after propranolol by about a third. The increased PGE efflux into CSB during CA was normalized after propranolol and quinidine if the CA was abolished or the cardiac rhythm improved. Lidocaine did not modify the increase in PGE efflux, despite the abolishment of CA. The increase in PGF2 alpha efflux was not influenced by antiarrhythmic drugs. The cyclic AMP and cyclic GMP in CSB remained unchanged during ouabain induced arrhythmias or after propranolol. The increased efflux of PGE into CSB during aconitine and ouabain induced CA and its abolishment by propranolol support the hypothesis that PGE participates in the modulation of increased sympathetic tone during CA. PMID- 6269138 TI - [Effect of cold and emotional stresses on plasma cyclic nucleotides of normal adults (author's transl)]. PMID- 6269139 TI - [The F-wave in healthy subjects - origin, derivation, standardization]. AB - The determination of the maximum F-wave conduction speed by means of the photographic superposition technique is a method that can be carried out in a technically simple manner and can give an insight into the peripheral motor neuron up to the anterior horn cell. The values can be determined in a more exact manner than the respective motor conduction speeds. Similar to the motor conduction speed, influencing factors are to be taken into consideration such as the temperature and the age of patients under ten years. The normal values for the N. ulnaris, radialis, fibularis and tibialis are submitted. PMID- 6269140 TI - [Balance of a therapeutic dwelling community -self-aid or care? (author's transl]. AB - A therapeutic dwelling community (TDC) which has been in existence for more than 3 years, is described in respect to its history of origin and development outside existing psychiatric institutions or facilities. After having been confronted with the unsatisfactory follow-up care of a group of relatively young, in most cases only medium-term hospitalized schizophrenic patients, the initiators of TDC developed a concept which was destined to strike a balance between care and activation of self-aid within the TDC in order to promote the mental stability and autonomy of the former patients. A description is given of the tension arising from the concept, between the claims on the part of the residents for care to be given to them on the one hand, and the expectations on the part of the guiding personnel with regard to the self-aid potential of the inhabitants, the description being given for different levels. The structure, dynamics and results of group activities within the TDC are also described. In this connection, an attempt is made to show up the individual and group-referred limits of self regulation of the inhabitants and of the therapeutic interventions; overstepping these limits endangers individual management of the TDC. An attempt is made to derive conclusions on the basis of the collected experience, which may be of importance for similar projects in respect of structure, financial jurisdiction, admission criteria etc. PMID- 6269141 TI - Effect of carbamazepine on CSF opioid activity; relationship to antidepressant response. AB - Carbamazepine, a drug useful in the treatment of trigeminal neuralgia and temporal lobe epilepsy, has recently been found to have positive psychotropic effects in patients with manic and depressive illness. The possible effect of carbamazepine on opioid activity in cerebrospinal fluid (CSF) were assessed in patients with affective disorders using a radioreceptor assay that detects total opioid binding activity. No effect of carbamazepine was noted on CSF total opioid activity, although conclusions about its possible effects on discrete opiate systems must await other methodologies. Initial medication-free levels of opioid activity were positively correlated with the degree of antidepressant response to carbamazepine. PMID- 6269142 TI - Relationship between urinary free cortisol and CSF opioid binding activity in depressed patients and normal volunteers. AB - We investigated the relationship between hypothalamic-pituitary-adrenal (HPA) activity, as measured by 24-hour mean urinary free cortisol (MUFC), and cerebrospinal fluid (CSF) opioid activity in patients with major affective disorder and normal volunteers. Among depressed patients, but not normal volunteers, mean 24-hour urinary cortisol values were significantly correlated with CSF opioid activity measured by radioreceptor assay, but were not significantly correlated with beta-endorphin immunoreactivity measured by radioimmunoassay. MUFC, as expected, was significantly higher in depressed patients than in normal volunteers. Mean values of CSF opioid activity and beta endorphin immunoreactivity did not differ significantly in the two groups. The positive opioid-MUFC correlation found in the depressed group appeared to depend on patients who were cortisol hypersecretors. These data, using relatively crude measures of cortisol and opioid activity, are suggestive of a relationship between these two systems, particularly under "activated" conditions such as those observed in depression. PMID- 6269143 TI - Functional reassembly of membrane proteins in planar lipid bilayers. PMID- 6269144 TI - Rheumatoid arthritis and pseudo-rheumatoid arthritis in calcium pyrophosphate dihydrate crystal deposition disease. AB - Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease can lead to many clinical syndromes. One syndrome simulates rheumatoid arthritis and is thus called "pseudo-rheumatoid arthritis." Since some patients have true rheumatoid arthritis with CPPD crystal deposition disease, the clinician may have difficulty differentiating those patients from others who have the pseudo-rheumatoid syndrome. Such a diagnostic problem can be solved radiographically. Eleven patients with CPPD crystal deposition disease were studied; five had true rheumatoid arthritis and six had pseudo-rheumatoid arthritis. Because osseous erosions were not apparent in the arthropathy of uncomplicated CPPD crystal deposition disease, the detection of skeletal erosive changes indicated a true rheumatoid arthritis process. PMID- 6269145 TI - Evaluation of the inferior vena cava by sonography and venography in children with renal and hepatic tumors. AB - Ultrasonography was used to examine 81 children with intra-abdominal or retroperitoneal malignancies for tumor extension into the inferior vena cava (IVC). In seven of the 18 patients with Wilms tumors and three of the seven patients with hepatic tumors, the IVC ws sonographically abnormal. Venography was also performed in five patients with Wilms tumors. However, percutaneous transfemoral venacavography did not always allow differentiation between extrinsic compression and intracaval tumor. It is suggested that venacavography, when necessary, should be performed via the brachial vein route and that the catheter be advanced into the right atrium. If an injection in this chamber does not result in enough reflux into the retrohepatic IVC for adequate evaluation, the catheter should be advanced into the IVC and a second injection made. However, ultrasonography is the preferred modality for evaluation of the IVC in children because it is the most accurate method and is noninvasive. Real-time ultrasonography makes it possible to distinguish between tumor extension into the lumen of the IVC and extrinsic compression of the vessel. PMID- 6269146 TI - Endogenous opioids and cyclic AMP. PMID- 6269147 TI - Role of chromatin structure, histone acetylation, and the primary sequence of DNA in the expression of SV40 and polyoma in normal or teratocarcinoma cells. PMID- 6269149 TI - Multiprotein interactions in strand cleavage of DNA damaged by UV and chemicals. PMID- 6269148 TI - Recent developments in the enzymology of excision repair of DNA. PMID- 6269150 TI - Induction and enhanced reactivation of mammalian viruses by light. PMID- 6269151 TI - Enzyme studies of phi X174 DNA replication. PMID- 6269152 TI - [Transfer of ACTH stimuli to adrenocortical mitochondria (author's transl)]. PMID- 6269153 TI - [Simple method of radioisotopic diagnostics of the osseo-arthricular system (author's transl)]. PMID- 6269154 TI - Risk assessment studies of E. coli host-vector systems. AB - These studies have demonstrated the poor survival of E. coli K-12 in the human and mouse gut and the absence of detectable transfer of pBR322 to endogenous intestinal flora. Even in the presence of mobilizing plasmids, no mobilization of pBR322 was detected, and transfer of the transferable plasmids was greatly reduced in the gut. Colonization of the mouse intestine by E. coli was shown to be affected by spontaneous chromosomal mutations to Sm or Rif resistance; these derivatives were weak competitors for colonization in the presence of the original E. coli K-12 organism. Moreover, E. coli K-12 appeared to be at a selective disadvantage in the human and mouse gut since even antibiotic selection failed to increase its survival. A background of data has been accumulated on the frequency of lambda, and M13 phages, and amber-suppressible bacteria in natural human and animal populations. These data should be useful to present and future risk-assessment evaluations. The frequency of antibiotic resistant coliforms in fecal samples from different human and animal populations was found to high. In the present study, antibiotic resistance was very common in both hospitalized and non-hospitalized populations. The percentage of resistant coliforms within individual specimens, however, was higher in patient population. PMID- 6269155 TI - The effect of cholecystokinin octapeptide on pituitary-adrenal hormone secretion. AB - The purpose of this investigation was to determine the influence of cholecystokinin octapeptide (CCK-OP) on pituitary-adrenal hormone secretion. CCK OP at a dose of 5 microgram/kg (i.p.) elevated plasma corticosterone from 27 to 43 microgram/100 ml in one experiment and from 12 to 50 microgram/100 ml in a second experiment. Lower doses of CCK-OP (0.5 microgram/kg) elevated corticosterone from 12 microgram/100 ml to 20 microgram/100 ml. CCK-OP (1, 10, and 100 ng/ml) had no effect on ACTH-induced corticosterone released by isolated adrenal cells in vitro when tested in the presence of 50 pg of ACTH1-24. 100 and 500 ng of CCK-OP resulted in an increased pituitary ACTH release equal to 123% (n.s.) and a 206% (P less than 0.05) of control, respectively. In comparison, a 3/5 hypothalamic stalk median eminence equivalent increased ACTH release to 313% of control (P less than 0.05). The exact mechanism of this CCK effect on pituitary ACTH release is unknown. Although it is likely that the direct effects on the pituitary in vitro represent a pharmacologic and not a physiologic effect of this peptide, in vivo doses are between doses used for pancreatic effects and satiety effects suggesting that there may be a physiologic stimulating action of this peptide on the hypothalamic-pituitary-adrenal axis but at a level above the adrenal and pituitary. PMID- 6269157 TI - [Contribution of embolization to the treatment of nasopharyngeal fibromas]. PMID- 6269156 TI - The mechanisms of hormone and drug actions on fatty acid release from adipose tissue. PMID- 6269158 TI - [Endopharyngeal approach to mixed tumors of the parotid]. PMID- 6269159 TI - [Mucosecreting papillary adenocarcinoma of the salivary gland]. PMID- 6269160 TI - [Comparative randomized study on the clinico-bacteriological effectiveness of mecillinam versus cotrimexazole in shigellosis]. PMID- 6269161 TI - [Inhibition of the cholestatic enzyme 5'-nucleotidase by high levels of bilirubin]. PMID- 6269162 TI - [Hepatocarcinoma caused by Thorotrast]. PMID- 6269163 TI - [Prolonged angina versus acute non-transmural myocardial infarction. Use of cardiac gammagraphy with technetium pyrophosphate]. PMID- 6269164 TI - Biosynthesis and mechanism of action of nerve growth factor. PMID- 6269166 TI - Polypeptide hormones: intracellular receptors and internalization. PMID- 6269167 TI - Nephrogenous cyclic AMP. PMID- 6269165 TI - Insulin receptors, receptor antibodies, and the mechanism of insulin action. PMID- 6269168 TI - [Peliosis hepatis, oral contraceptives and hepatic carcinoma: a case treated surgically (author's transl)]. PMID- 6269169 TI - Paralytic poliomyelitis: Old dogmas and new perspectives. AB - No poliovirus vaccines can be expected to eliminate the paralytic poliomyelitis that is caused by nonpolio enteroviruses or the cases that have been and continue to be diagnosed erroneously as paralytic poliomyelitis. Polioviruses have been recovered from the feces of patients with paralytic disease that is definitely not poliomyelitis, and very rare cases of so-called "vaccine-associated" paralytic disease cannot be regarded as having been caused by the vaccine virus when it is present in the feces and even more so when no virus is recovered. Surveys for residual poliomyelitis paralysis in tropical countries indicate an average annual incidence that is as high or higher than in the United States in the prevaccine era. Oral poliovirus vaccine has eliminated paralytic poliomyelitis caused by polioviruses in many temperate-climate countries in which a large proportion of children remain unvaccinated or incompletely vaccinated. Oral poliovirus vaccine can also eliminate paralytic poliomyelitis from tropical countries but a different strategy is needed for using the vaccine. PMID- 6269170 TI - Treatment of paracoccidioidomycosis with ketoconazole. PMID- 6269171 TI - [Changes of certain enzymes and glutathione status in rat liver regeneration (author's transl)]. PMID- 6269172 TI - [Monitoring cancers of the uterine cervix after treatment]. PMID- 6269173 TI - [Mohr's syndrome : type II orofaciodigital syndrome (author's transl)]. AB - Mohr's syndrome consists of an association of three types of malformation : oral, facial, and digital. It is very similar, therefore, to the syndrome of Papillon Leage and Psaume. Apart from this, precise, constant characteristics can be recognized which identify it as a separate entity. Firstly, the genetic mode of transmission differs. Secondly, clinical signs are dominated by the frequency and severity of the distal lesions, such that bilateral syndactyly of the big toe is a key element in the differential diagnosis. PMID- 6269174 TI - [Asymmetric craniofacial stenosis with syndactyly : Saethre-Chotzen syndrome? (author's transl)]. PMID- 6269175 TI - Purification of human lung angiotensin-converting enzyme. AB - Angiotensin-converting enzyme (ACE) was purified about 7000 times from human lung tissue obtained at thoracotomy. After solubilization with Triton X-100 and sonication, ion exchange DEAE cellulose chromatography and Sepharose 4B gel filtration were performed. After gel filtration a 5-6 fold increase in purity was achieved by neuraminidase treatment of the protein and recycling over DEAE cellulose. Purity was established in SDS electrophoresis and on electrofocusing 125I-labelled purified protein and these procedures indicated a molecular weight of about 150,000 and pI value of 4.5, respectively. The purified protein split Angiotensin I and this action was inhibited by Captopril (Squibb 14,225), specific inhibitor of ACE (kininase II). The Km value for the synthetic substrate hippuryl-histidyl-leucine was 3.7 X 10(-4) mol/l. The IC50 of Captopril when inhibiting human lung ACE action on the same substrate, was 4.5 X 10(-9) mol/l. PMID- 6269177 TI - [Posttraumatic soft tissue sarcoma: a case study of a malignant fibrous histiocytoma of the elbow joint which appeared six and a half years after a severe injury]. AB - A 25-year-old patient was treated for a malignant fibrous histiocytoma of the elbow which appeared 6 3/4 years after a severe injury at this site. The reasons for assumption of a causal relationship between the trauma and tumor development are discussed. PMID- 6269176 TI - [Transfer of information from T and B lymphocytes during immune response: role of extracellular DNA]. AB - Human lymphocytes obtained from donors exhibiting different allotypes were separated into B and T subpopulations and cultured in presence or in absence of UV-inactivated Herpes simplex virus. Isolated B or T cells did not produce antiherpetic activity. The B lymphocytes, cultured in presence of the supernatant collected from virus exposed T cells or in the presence of DNA extracted from this supernatant, synthesized an antiherpetic antibody carrying allotypic markers of the T cell donor. PMID- 6269178 TI - [Central nervous system metastases in small cell lung cancer]. AB - Forty of 156 patients (26%) with small cell lung cancer developed central nervous system metastases (CNS metastases) in the course of the disease. CNS metastases were found in 8 patients at the time of the initial diagnosis and 32 patients had subsequent CNS involvement. CNS metastases were usually concurrent with disease progression at other sites and became more frequent as survival increased. With a median survival of 6 months in 1973 19% of patients developed CNS metastases as compared to 35% in 1978, when median survival had increased to 9.5 months. The value of prophylactic cranial irradiation is discussed. PMID- 6269179 TI - [Long-term tumor-free surviving patients with anaplastic small cell bronchial cancer]. AB - Report on 12 patients with small cell lung cancer who achieved disease-free survival for over 24 months after initial therapy. All the cases were classified as limited disease. Median age was 62 years and median performance status 0. Only 2 patients had weight loss of more than 5% in the six months prior to the diagnosis. Four patients were treated by local therapy alone (surgery in 3, radiotherapy in 1). Eight patients received systemic treatment (chemotherapy in 4, chemotherapy plus radiotherapy in 4). Median duration of cytostatic treatment was 17 months, with 3 of 8 patients receiving chemotherapy for less than 6 months. Three patients relapsed 27, 34 and 54 months after initial treatment. Median survival is 52 + months. It is concluded that long term disease-free survival can be achieved in patients with limited disease small cell lung cancer, even where initial treatment is relatively short. PMID- 6269180 TI - Lithium increases serotonin release and decreases serotonin receptors in the hippocampus. AB - The effects of long-term lithium administration on pre- and postsynaptic processes involved in serotonergic neurotransmission were measured in rat hippocampus and cerebral cortex. Long-term lithium administration increased both basal and potassium chloride-stimulated release of endogenous serotonin from the hippocampus but not from the cortex. Serotonergic receptor binding was reduced in the hippocampus but not in the cortex. These results suggest a mechanism by which lithium may stabilize serotonin neurotransmission. PMID- 6269181 TI - Growth arrest and morphological change of human breast cancer cells by dibutyryl cyclic AMP and L-arginine. AB - The growth in vitro of human breast cancer cells, line MCF-7, was inhibited by a daily supplement of L-arginine (1 milligram per milliliter). Arginine acted synergistically with dibutyryl adenosine 3',5'-monophosphate (cyclic AMP) (10(-6) molar) to enhance the growth inhibitory effect: the cell replication ceased completely within 2 days after treatment. The growth arrest accompanied a change in cell morphology and was preceded by increases in the cellular concentration of cyclic AMP, adenylate cyclase, and type II cyclic AMP-dependent protein kinase activities as well as a decrease of estrogen binding activity. The results suggest that growth of human breast cancer cells is subject to cyclic AMP mediated regulation and that arginine may play a specific role in this process. PMID- 6269182 TI - Hindbrain GABA receptors influence parasympathetic outflow to the stomach. AB - Blockade of gamma-aminobutyric acid receptor function by direct microinjection of bicuculline into the nucleus ambiguous in cats produced a marked increase in gastric motility which was mediated by the vagus nerve. This effect was reversed by muscimol. These data indicate that the nucleus ambiguous may be an important brain site influencing gastric function and that the neurotransmitter controlling parasympathetic overflow from this nucleus to the stomach is gamma-aminobutyric acid. PMID- 6269183 TI - [The nosology of depressions (author's transl)]. AB - The author presents the classical nosology of depressive states, with its five main categories (depression belonging to the manic-depressive psychosis, involutional organic-symptomatic, psychogenic, depressive personality disorder). He comments on the two recent modifications: distinction between the unipolar and bipolar forms, suppression of the category of involutional depression. He presents finally the two modern nosological systems, ICD 9, a relatively traditional nosology, and DSM III whose fundamental principles and categories are discussed. PMID- 6269184 TI - [Biochemical aspects of depression (author's transl)]. AB - Alterations of brain monoamines in animals produced by antidepressant administration suggest that depression may involve these monoamine systems. In an attempt to examine these possibilities, investigations of central noradrenergic and serotoninergic metabolism in depressed patients were performed but at times these have failed to produce convincing results. The exact mechanism of action of antidepressants remains also unknown. Nevertheless recent findings show that chronic treatment induces changes in the sensitivity of the beta-noradrenergic and serotoninergic receptors closely correlated in time with clinical improvement and common to all types of antidepressant drugs. Tricyclic anti-depressants also act directly as antagonists on alpha-adrenergic, cholinergic and H1, and H2 histaminergic receptors and it has been assumed that these pharmacological properties account for the side-effects of these drugs. Recently, high affinity binding sites for 3H-imipramine were demonstrated, the significance of which is still unresolved. PMID- 6269185 TI - [Sleep and depression (author's transl)]. AB - This critical review of the literature concerns the electrophysiological studies of sleep applied to depressed patients. While the (phenomenological) studies confirm the actual sleep disturbances in most patients and at certain stages of the depressive episodes, the (parallelistic) studies failed to evidence any strict correlation between quantified sleep data and nosographical classifications of depressions. The reductionistic) studies, searching into sleep measurements indices of specific biochemical disturbances also lead to contradictory and questionable conclusions. The explanation of this negative assessment is not to be found in methodological deficiencies but must be searched at the level of the theoretical approach of the problem. PMID- 6269186 TI - [Psycho-endocrinology in affective disorders (author's transl)]. AB - The possible actions of hormones on the central nervous system are yet poorly known. The relationships between hormonal disturbances and affective disorders are very difficult to interpret. Now, the more usual hypothesis on the pathogeny of these affective disorders is a dysfunction of catecholaminergic neuromediation. In this view, different hormonal anomalies can be involved: participation of hypothalamo-pituitary-adreno-cortical axis, hypothalamo pituitary-thyroid axis, hypothalamo-pituitary-gonadic axis and intervention of growth-hormone axis. These different explanations are supported by some experimental and clinical data but none is really predominant. In this paper, the modifications of growth-hormone responses in some affective disorders are shown as very interesting and permitting some precisions in etiologic diagnosis of some affective disorders. PMID- 6269187 TI - [Genetic analysis of affective disorders (author's transl)]. PMID- 6269188 TI - [Psychopathology of depression (author's transl)]. AB - Depression can be observed in individuals with any type of personality structure especially in situations in which change is involved. The mourning model is not sufficient to account for the type of difficulties, the particular mood and the lowered self-esteem so characteristic of depressive syndromes. The study of the psychological development of children helps us to sort out those situations which are of depressive type. However, not a single past incident during childhood can be clearly singled out as a causal factor of adult depression. Depressed adults as well as neurotics, psychotics, psychopaths or alcoholics have in common the fact that they have experienced early separation more often than control subjects. The attempts to isolate a particular aspect of the premorbid personality of depressed individuals are not at all conclusive. The notion of the typus-melancholicus (Tellenbach) has, however, the value of emphasizing the limiting character of these personalities: the need for a restricted perimeter of activity, limitations as concerns daily goals and painful sensitivity to change. The psychological reconstruction of depression can be done only after the event. PMID- 6269189 TI - [Epidemiology of depression (author's transl)]. AB - The authors use a number of recent studies to illustrate what can be achieved by exemplary work on depression. One of the studies is concerned with incidence in one community and others with comparisons of clinical and psycho-social aspects of depression in different cultures. They underscore the importance of making the distinction between conspicuous and hidden morbidity when measuring morbidity rates. In clinical practice, psychiatrists see only a narrow range of the depressive spectrum, which is made up of many different clinical entities varying in symptomatology and severity. Attempts to compare the prevalence of these conditions are often frustrated by problems of definition and classification of the clearly morbid states, in addition to the difficulties inherent in differentiation between these states and the normally accepted range of mood variations. These points are probably largely responsible for wide differences in the prevalence rates published by different authors and for different countries. The latter part of the discussion emphasizes the scientific importance of transcultural comparisons of depressive symptoms and points out the need to assess the influence of socio-cultural changes upon the frequency and types of depressive states. Throughout all this discussion, the necessity of standardized instruments of clinical assessment is underlined. PMID- 6269190 TI - [Biological treatments of depression (author's transl)]. AB - The different biological treatments of depression are first reviewed from an analytical point of view. The drugs are divided in three groups: the classical tricyclic antidepressants, the MAO inhibitors and the recent antidepressants. Some drugs with potential antidepressant properties are also studied. The other biological treatments of depression include electroconvulsive therapy and sleep deprivation. In a second step, the characteristics of these different treatments are detailed. Finally, the strategy of a drug treatment is considered with regard to the choice of the best drug and the best dosage for a given depressed patient. PMID- 6269191 TI - [The new problems in psychiatry (author's transl)]. AB - Modern psychiatry, born of a movement created by Pinel in France and Tuke in England, has set aside the rejection of mental patients, and centred the study of mental diseases in France on the predominance of periodic psychoses, and therefore curability. Another movement, however, arising from the discovery of biological psychiatry has focused psychiatry on schizophrenia and incurability. This is a serious and damaging error. Furthermore, the discovery of toxic causes by Moreau de Tours, and more recently, of experimental catatonia, has enabled psychopharmacology to widen etiological and therapeutic fields. Even so, psychiatry is menaced by a return to the past, perhaps to the point of rejection of mental patients, and this has been accentuated by psychoanalysis, which rejects (psychotics) in favour of neurotics, and by the concept of blocking in incurability. This regression is beginning to affect legislation, with the threat of a return to the arbitrary, and to the social decline of patients, following the recent law on the legally incapacitated. PMID- 6269192 TI - [Effects of tiapride infusion on plasma levels of beta-endorphin, prolactin and dopamine in patients with pain from cancer (author's transl)]. AB - Tiapride, a substituted benzamide, exerts an antalgic effect in man. To examine the possibility that tiapride analgesia might be related to a mechanism involving a release of endogenous opioids, the acute effects of an intravenous injection of the drug on plasma radioimmunoassayable beta-endorphin were studied in patients with pain from cancer (placebo-tiapride double-blind randomized trial). Seeing that substituted benzamides affect prolactin secretion, the plasmatic levels of prolactin and dopamine, a known factor inhibiting prolactin release, were studied as well. The tiapride infusion produced a slight but significant increase in plasma beta-endorphin level, an early and significant increase in plasma prolactin, and a sudden and highly significant decrease in plasma dopamine. These results are compatible with the hypothesis that tiapride influences the neuroendocrine system. PMID- 6269193 TI - [The effect of bromocriptine on the course of dementia (author's transl)]. AB - The effect of bromocriptine on the course of dementia in the aged is reported by the authors. This study is based on a protocol taken from genetic psychology and concerns 25 patients. A posology of 5 mg was generally used except in 4 patients who received 10 mg. The clinical results show improvement in the motor, operative and memory functions as well as in affect and behavior. The electroencephalographic results show in 2/3 to 3/4 of the cases, the reappearance of alpha rhythm, an improvement in the arousal reaction and the disappearance of the slow delta rhythms. The comparison between the clinical and the electroencephalographic results shows a remarkable electro-clinical concordance. PMID- 6269194 TI - [Agitation in the elderly (author's transl)]. AB - Agitation in the elderly is a common behaviour disorder. The clinical picture is quite variable: aggressive reactions, anxious agitation, agitation associated with confusion: sometimes, the agitation occurs in episodes, especially during the night. These types of agitation have two basic causes: confusion and dementia. In some cases, they are the clinical expression of an angry, hostile or excited state. In agitation associated with confusion, one must eliminate an intoxication, a neurological disorder, an infection, and notably a past head injury which may have gone undetected. Therapeutic measures are discussed. PMID- 6269195 TI - [Psychological and psychiatric emergencies in child and adolescent. Specificity and diversity of the possible situations and responses (author's transl)]. AB - Two situations, which may of course interfere, are described in the field of psychological and psychiatric emergencies in child and adolescent: 1) therapeutic emergencies, true emergencies, linked to acute mental suffering or even distress in the child which it is important to relieve quickly. They are not always the object of an acute request for medical care, and when such a request is made, it is rarely based on what the child feels, but much more on noisy or troublesome behaviour or somatic manifestations of the latter, this last possibility producing a masked psychiatric emergency very characteristic of this age; 2) environmental emergencies represent a second form of emergency, defined by a situation which appears when the child's family or tutors suddenly decide that they can no longer face such a behaviour or such symptoms in the child. Intolerance then appears, or even rejection of the child from his home. The authors were led to determine this double dimension, concentrating their attention on the first few years of life, childhood from 4 to 5 years to 11 or 12 years and adolescence. Insisting on the dual necessity, even in emergency cases, of sufficient reflexion and necessary concentration of interest on problems as they are presented by the family, the authors describe the various stages of an emergency: entering into contact, evaluation of the situation, choice of the emergency procedure: gaining time or admission to hospital in a specialized unit. They end by taking into consideration the fact that one is never sufficiently attentive to the child himself and to his own way of dealing with the situation. PMID- 6269196 TI - [The sleep disorders in children (author's transl)]. PMID- 6269197 TI - [Tiapride and verbal or motor stereotypies (author's transl)]. AB - Various repeated and involuntary stereotypies may affect some patients. Limb muscles and/or language may be involved in these phenomenons. Tiapride, per os, at a dosage of 300 to 600 mg/day leads in most of cases to a total disappearance or a perceptible improvement of these pathological manifestations. There were neither side effects in the patients reported herein, nor iatrogenic parkinsonism. In this paper the mechanism of action of this drug, in relation to its other therapeutic effects, is discussed. PMID- 6269198 TI - [The physician between the delinquent and the judge (author's transl)]. AB - The authors examine three situations in which the physician intervenes between the delinquent and his judge. 1) The Drug Addicts: it is important to distinguish in behavioural disturbances the difference between delinquency and addiction. According to the Law of the 31st of December 1970, the physician becomes an auxiliary to the judicial process. In fact, the opportunity of such an encounter between the physician and the addict can be beneficial to both of them. 2) The juvenile delinquent: The assumed responsibility of the juvenile delinquent falls, on one hand, on the care of his personality, and on the other hand, on his way of life. 3) Article 64 of the Penal Code: this determines the responsibility or the irresponsibility of the delinquent depending upon eventual mental disease. The doctor's position is delicate, in certain cases, it is important to avoid excessive medicalization of a social problem, in others it is necessary to advise the appointment of an expert. PMID- 6269199 TI - [Megalocytic anemia of alcoholics and folic acid (author's transl)]. AB - Megalocytic anemia of alcoholics is due to the deficiency of folic acid: the proof is the serum hypofolemia. The mechanism is complex and due to : a dietary deficiency; a malabsorption; an insufficiency of conversion of polyglutamate to monoglutamate; a liver deficiency; a specific effect of alcohol on the folate absorption. Alcohol has a toxic effect on the marrow and inhibits the folic acid. PMID- 6269200 TI - [Hypersensitivity pneumonitis in children. A study of 5 cases (author's transl)]. AB - Five cases of hypersensitivity pneumonitis in children are reported. Four had the pattern of bird breeder's disease and one of aspergillus lung hypersensitivity. All were clearly defined by clinical, radiological, functional and immunologic features. The possible difficulties in diagnosis are emphasized. The disease might be frequently overlooked and its frequency underestimated in children. The diagnostic value of precipitating antibodies is discussed. Although some immunologic studies suggest immune complex mechanisms, recent experimental and clinical data are in favor of a role for cell-mediated immunity. In addition whether or not immunological damage is to occur and result into disease depends not merely upon the characteristics of the antigen exposure. Genetic and/or acquired individual differences in immune reactivity can play a definite role as well. The risk of secondary pulmonary fibrosis and chronic respiratory failure in untreated patients is emphasized. Immunologic and functional tests for identification of the provoking antigen and ceasing of contamination exposure are urgent : they are also useful for monitoring steroid therapy. PMID- 6269201 TI - [Intra-articular injection of radioactive yttrium 90 in the hemophilic arthropathies. About nine cases (author's transl)]. AB - The authors report 9 cases of intra-articular injection of radioactive yttrium 90. They specify the very place of this therapeutics in the hemophilic arthropathies treatment. Y 90 seems to give better results than osmic acid but cannot be used before the full growth. Thereby the authors point out the respective directions of their use. PMID- 6269203 TI - [Vascular epilepsy: clinical, electroencephalographic, and computerized tomographic aspects (author's transl)]. AB - The authors report 31 cases of "vascular epilepsy" among 280 cerebral strokes confirmed by cranial computerized tomography. A high incidence of ischemia (28 cases : 90%) is noted. Epileptic seizures are initial (14 cases) or sequellar (17 cases) manifestations of cerebral stroke. Partial seizures are the most frequent (58%), particularly "Jacksonian" motor fits, which, when initial, often lead to status epilepticus. Frequency and bad prognosis of initial status epilepticus are pointed out. PMID- 6269202 TI - [Gamma-phlebography of the upper limbs (author's transl)]. PMID- 6269204 TI - [The neuro-ophthalmological complications in SLE (author's transl)]. AB - In a 44 years old woman, a flare up of polyarthritis becoming positive for sero reaction at the time of hospitalization, is referred to an earlier unknown SLE. The bilateral optic neuritis which began 15 years earlier, while she was pregnant, simultaneously with a bilateral carpal tunnel syndrome is retrospectively related to the SLE. Such an optic neuritis is rare, its clinical features are specified among the neuro-ophthalmological complications in SLE. Very often optic neuritis is associated with myelopathy. Hypercytosis with moderate elevation of albumin C.S.F., a high level of cyclic GMP, and a low concentration of IgG in C.S.F., are found in central neurological complications in SLE. Other biological alterations are described but both their signification and their interest, as well for diagnostic as for therapeutic supervision, are unknown. Neuropathological findings show either vasculitis or demyelinizing lesions. This case shows the therapeutic problems of such medical situations. PMID- 6269205 TI - [Computed tomography in the giant intracranial aneurysms (author's transl)]. PMID- 6269206 TI - [Alpha-1-antitrypsin and cystic fibrosis (author's transl)]. AB - A methodical study of the alpha-1-antitrypsin serum level and the Pi type in 69 CF children, 156 CF heterozygote parents and 200 blood donors from Paris, has been made. Although the PiZ allele frequency was found to be higher in the CF population, especially in fathers, than in the reference population, the difference is not statistically relevant. Therefore there does not seem to be a relation between cystic fibrosis and the Pi alleles system. PMID- 6269207 TI - [Operative risk in cholelithiasis. 5 433 surgical interventions (author's transl)]. AB - Mortality and morbidity of surgical treatment of gallstones are analysed through a series of 5 433 operations : 3 885 for chronic cholecystitis; 844 for choledocholithiasis, 564 for acute cholecystitis, 96 for odditis, 31 for internal fistula, 13 for gallstone ileus. The overall mortality rate is 1,53%, the morbidity rate 8,32 % but significant differences are found related to sex, age, stage of disease and operating procedure: for example cholecystectomy for chronic cholecystitis in patients beyond 60 years has a mortality rate of 0,2%; in choledocholithiasis, after 70 years the mortality rate is 9,8% . Analysis of deaths and complications shows that mortality and morbidity can be reduced by a better selection of cases and various preventive measures. PMID- 6269208 TI - [Massive edema of the ovary. A clinicopathologic study of one case and review of the literature (author's transl)]. AB - The first observation of a massive ovarian edema with frozen-section examination of a biopsy specimen and ovarian preservation is related. A 27-year-old woman had a 12 cm right ovarian mass on twisted pedicle. After the ovary was untwisted and biopsied and while waiting for the frozen section study, the ovary returned to normal size and aspect. Ovarian preservation was decided. The elements of histopathologic diagnosis, in particular for a frozen-section examination of ovarian biopsy, are listed and discussed. Diagnostic difficulties must be solved by : clinical and peroperative macroscopic findings, a large biopsy specimen, allowing several frozen-section studies, in order to detect ovarian follicles scattered by the edema, which alone allows the affirmation of the diagnosis. PMID- 6269209 TI - [Sympathetic reflex dystrophy with hypofixation of technetium 99 m pyrophosphates on bone scintigraphy (author's transl)]. AB - A patient with sympathetic reflex dystrophy following injury to the right foot presented fairly typical clinical and radiological signs, though the hot phase was particularly short. Bone scan with technetium 99 m pyrophosphates demonstrated hypofixation, which, though extremely rare, has been previously reported in the published literature. The fact that isotopic bone hypofixation can occur during sympathetic reflex dystrophy should be recognised, as far from constituting an argument against the early diagnosis of this affection, it should enable the organic nature of the disorder to be confirmed, and assist the physician in making an early diagnosis. PMID- 6269210 TI - [Diffuse hemangioma of the liver. An unsuccessful cobalt therapy (author's transl)]. AB - With reference to the observation of a diffuse hemangioma of the liver in an adult patient, the authors note the various means of diagnosing the disease and list existing therapeutic possibilities. In the typical case, a laparoscopy points out the tumour but is not sufficiently precise to detect a possible extension. The angiography shows pathognomonic images. Isotopic methods are not specific. Treatment is poorly codified and may take the form of a ligature of the artery, embolization or irradiation. The latter, the most widespread type of treatment may cause more or less severe complications. PMID- 6269211 TI - [Prolymphocytic leukemia of T-cell type. Clinical, cytological, cytochemical and immunological studies (author's transl)]. AB - Prolymphocytic leukaemia (PL) is a rare variant of lympho-proliferative disorder, defined by Galton [21], which differs clearly from CLL by clinical, haematological and immunological features. Nevertheless like CLL, PL appears to represent predominantly a B cells monoclonal proliferation and cases of T-PL are rare. We report about another case of PL which was found to have T-lymphocyte characteristics and some clinical and immunological particularities. PMID- 6269212 TI - [Creutzfeld-Jakob disease: recent advances; biology of unconventional viruses (author's transl)]. PMID- 6269213 TI - [Ambulatory treatment of chronic alcoholics by tiapride (author's transl)]. AB - Tiapride is the only medication which may have a favorable effect simultaneously on the general behaviour, the tremor, and the digestive symptoms, of alcoholics. This study was carried out in 22 alcoholic patients. Each received, either one intramuscular injection of 100 mg or 200 to 300 mg orally, per day. In eleven cases results were very satisfactory and in nine improvement was very noticeable. The treatment failed in two cases. Anxiety, which was present in 20 cases, disappeared in 18. Tremor was observed in 8 patients and disappeared in all. Tolerance was excellent in all cases. No sedative side effects were observed. This is particularly important for these patients who were continuing their professional activities. PMID- 6269214 TI - [A case of permanent neurological sequelae by lithium intoxication during a thyrotoxicosis (author's transl)]. PMID- 6269215 TI - Joint scanning in rheumatoid arthritis: a literature review. PMID- 6269216 TI - Role of cholecystokinetic agents in 99mTc-IDA cholescintigraphy. AB - Cholecystokinin (CCK) and its C-terminal octapeptide analog, Sincalide, have been utilized in two separate roles for the evaluation of gallbladder disease. These are: (1) prior to cholescintigraphy to evacuate the gallbladder and optimized subsequent filling with radiotracers, and (2) to study contractile function of visualizing gallbladders on cholecystography and cholescintigraphy. As a preparation for 99mTc-IDA studies, it clearly facilitates earlier gallbladder filling in patients with chronic cholecystitis, thereby ruling out complete cystic duct obstruction. The problem lies in the fact that the use of CCK as a premedication markedly decreases the sensitivity of the study to detect chronic cholecystitis, since the findings become indistinguishable from patients with normal gallbladders. For this reason, the authors prefer to obtain delayed images, since chronic cholecystitis is frequently associated with gallbladder filling beyond the first hour. The role of CCK in detecting abnormal gallbladder function in the normally visualizing gallbladder also is controversial. Other studies as well as the author's experience suggests that as much as one-forth of positive cases may be associated with normal gallbladders at surgery and often even on microscopic examination. However, most importantly, the great majority of these patients are relieved of their symptoms following surgery. It appears reasonable that CCK or Sincalide cholecystography or cholescintigraphy may be detecting functional abnormalities before anatomic changes occur and can, therefore, serve as a useful examination in selecting symptomatic patients who may benefit from cholecystectomy. PMID- 6269217 TI - Mesothelioma--the role for radiation therapy. PMID- 6269218 TI - Assessment of bone marrow and body iron stores: old techniques and new technologies. PMID- 6269219 TI - Hormonal control of preterm and term parturition. PMID- 6269220 TI - Biology and biochemistry of myometrial contractility and cervical maturation. PMID- 6269221 TI - DNA reassociation and base composition. PMID- 6269222 TI - Cytochrome patterns in classification and identification including their relevance to the oxidase test. PMID- 6269223 TI - Plasmids. PMID- 6269224 TI - Immunological detection of food-poisoning toxins. PMID- 6269225 TI - On the use of general network functions in the evaluation of noise spectra obtained from epithelia. PMID- 6269226 TI - Ion activity measurements in single renal tubules. PMID- 6269227 TI - Sodium entry step in transporting epithelia: results of ligand-binding studies. PMID- 6269228 TI - Electrical properties of amphibian urinary bladder epithelia. IV. The current voltage relationship of the sodium channels in the apical cell membrane. PMID- 6269229 TI - Current-voltage properties of the active sodium transport pathway across rabbit colon. PMID- 6269230 TI - Impedance analysis in epithelia. PMID- 6269231 TI - Neurologic complications of infectious mononucleosis after steroid therapy. PMID- 6269232 TI - [Clinical aspects of epidemic rotavirus gastroenteritis in adults]. PMID- 6269233 TI - [Possibilities of scintigraphy and laparoscopy in the diagnosis of stomach cancer metastases to the liver]. PMID- 6269234 TI - Ranitidine in uncomplicated duodenal ulceration. A double-blind endoscopically controlled trial. AB - Fifty patients with endoscopically proven uncomplicated duodenal ulcers were given either ranitidine 150 mg twice daily or placebo for 4 weeks in a randomized double-blind study. After 4 weeks 76% of patients on ranitidine showed healing. Fifteen (60%) were completely healed, 5 (20%) were partly healed, and 5 had active unchanged ulcers. Of the patients on placebo 6 (27%) were completely healed, 6 (27%) were partly healed, 10 had active unchanged ulcers and 3 had absconded. Grouping partly healed with active ulcers, a Z value of 2,23 was obtained in the Mantel-Haenszel test (P = 0.013 in favour of ranitidine over placebo). Of 10 patients who were partly healed or had active ulcers after being given ranitidine in the first stage of the study, 7 healed on one further course in an open study and 3 still had active ulcers after two further courses. Of 16 patients who were partly healed or had active ulcers after 4 weeks on the placebo, 3 healed on one course of ranitidine, 6 healed on two courses, 6 still had active ulcers after two courses, and 1 absconded. No side-effects were noted. Ranitidine is a safe and effective drug for the treatment of active duodenal ulceration. PMID- 6269235 TI - [Hypertension, grand mal epilepsy, intestinal dyskinesia, sensitive motor neuropathy and hyponatremia resulting from acute vincristine overdosage (author's transl)]. PMID- 6269236 TI - Evidence that Benzo(a) pyrene-resistant, aryl hydrocarbon hydroxylase-deficient variants of mouse hepatoma line, Hepa-1, are mutational in origin. AB - Treatment of Hepa-1 with N-methyl-N'-nitro-N-nitrosoguanidine, ethyl methanesulfonate, UV light, or ICR-191G, increased the frequency of benzo(a)pyrene-resistant (BPr) clones. The relative efficacies of the mutagens at increasing the frequency of BPr clones correlated with their efficacies a inducing 6-thioguanine-resistant clones. Evidence was obtained that the mutagens induced the BPr variants rather than selecting for BPr cells that preexisted in the treated cultures. All variants tested had reduced AHH activities and phenotypes that were stable over time in culture. Certain "leaky" variants with residual AHH activities and low cloning efficiencies in BP were further selected in BP and subclones isolated. Half the subclones were indistinguishable from their parents, while the majority of the remainder retained at least half of their parents' AHH activity. The marked stability of the phenotype of the variants, and their induction by mutagens, suggests that they are bona fide mutants. PMID- 6269237 TI - Expression of SV40 T antigen in finite life-span hybrids of normal and SV40 transformed fibroblasts. AB - The fusion of normal human fibroblasts with SV40-transformed human fibroblasts resulted in hybrid clones, 85% of which exhibited a finite in vitro life-span. Foci of rapidly dividing cells appeared in 15% of the hybrid clones. The cells within these foci repopulated the culture and could then be subcultured through more than 100 population doublings. One or two foci of dividing cells occurred per culture of 10(5) or more cells. The change to an indefinite life-span was, therefore, a rare event. All hybrid clones, including those that exhibited a finite in vitro life-span, expressed viral T antigen. Thus, even though viral DNA was present and being expressed in all hybrid clones, the senescent phenotype was dominant in these hybrids. PMID- 6269239 TI - Analysis of mammographically obvious carcinomas of the breast with benign results upon initial biopsy. AB - Although benign lesions of the breast may, on occasion, be indistinguishable from carcinoma on mammography, the presence of a typical malignant tumor justifies a strong roentgenographic impression which shoud be nearly 100 per cent accurate. During the past three years, 435 carcinomas of the breast were evaluated by xeromammography prior to surgial excision, 370 of which presented as palpable lesions. In six patients, the initial biopsy of a palpable area yielded benign results, despite a roentgenographic report indicating the presence of a carcinoma. Repeat mammography after biopsy documented the persistence of the suspicious area, all of which were carcinoma upon re-excision. Roentgenographic reappraisal is imperative in circumstances in which the biopsy results do not corroborate the roentgenographic findings. Preoperative needle localization is a useful adjunctive measure to ensure that a palpable area corresponds to a mass visible on the mammogram. PMID- 6269238 TI - Cyclosporin A and steroid therapy in sixty-six cadaver kidney recipients. AB - From nine to 18 months ago, 66 patients were given 67 randomly matched cadaveric kidneys with cyclosporin A and steroid therapy. Nine of the recipients were undergoing retransplantation. The over-all kidney survival rate to date has been 77.6 per cent, and 78.8 per cent of the recipients are dialysis-free. The patient mortality in this learning phase was 13.3 per cent. Nephrotoxicity, hepatotoxicity and other side-effects of cyclosporin A could usually be dealt with by dosage adjustments, making feasible the chronic use of this agent. One B cell immunoblastic sarcoma was encountered which was monoclonal. It was not responsible for death. Another patient had a perforation of the intestine from a lympho-proliferative reaction in which the B cells were polyclonal. After jejunal resection a year ago, there were no further complications. This lesion was not classified as a lymphoma. Both lympho-proliferative lesions were associated with a rise in antibody to viral capsid antigen of Epstein-Barr virus. Results of this study have verified the effectiveness and relative safety of cyclosporin A with steroids for immunosuppression in human recipients of cadaveric kidneys. PMID- 6269240 TI - Pharmacokinetics of a new water-soluble nitrosourea derivative (ACNU) in human gliomas. AB - The pharmacokinetics of a newly developed water-soluble nitrosourea derivative (ACNU) following a single intravenous injection was investigated in 11 patients with gliomas. A major portion of ACNU was excreted within 2 hours. The distribution rate was very fast, and the elimination rate tended to be slow. More than 50% of ACNU moves into the tissue compartment. ACNU tended to move into glioma tissue well. The ACNU level in glioma tissue was above 1.0 microgram/gm 30 to 60 minutes ater injections. ACNU was detected at a higher concentration in malignant gliomas than in benign gliomas. These results suggest that ACNU is taken up by tumor tissue relatively rapidly and eliminated slowly, which leads to effective manifestation of its antitumor activity. PMID- 6269241 TI - Biochemical subgrouping of benign breast disease to define premalignant potential. AB - To determine which subgroups of benign breast disease are likely to progress to malignant degeneration, a biochemical analysis of 3'5' cyclic adenosine monophosphate (cAMP) was run on several samples of breast tissue. cAMP is elevated in a progressive fashion from normal breast tissue to fibrosis, cystic mastitis, ductular hyperplasias, and finally to carcinoma. Correlation of cAMP levels in breast lesions with histopathologic grading of increasing epithelial proliferation confirmed the concept that there are subgroups within those lesions that have greater malignant potential. Benign breast lesions with significantly higher cAMP levels, although still lower than those of cancer, must be considered at higher risk for eventual malignant change. PMID- 6269242 TI - Operative and chemotherapeutic management of malignant glucagon-producing tumors. AB - Glucagon-producing tumors of the pancreas are among the rarest forms of islet cell tumors. Two patients are described in whom the characteristic dermatitis, glucose intolerance, weight loss, and anemia of the glucagonoma syndrome were due to a metastasizing islet cell carcinoma. In both, removal of the primary tumor with a distal pancreatectomy brought marked relief of all clinical symptoms for 1 and 2-year periods. Because streptozocin, the usual chemotherapeutic agent for these tumors, is quite toxic and frequently unsuccessful dimethyltriazenoimidazole carboximide (DTIC) was used for recurrence after operation. The first patient began taking DTIC when his rash reappeared and his immunoreactive glucagon (IRG) level rose to 6,000 pg/ml (normal, less than 200 pg/ml). Within 3 months, his rash was gone, and IRG level was 75 pg/ml. The second patient developed a neoplastic gastrocolic fistula and was extremely emaciated. With DTIC, the fistula healed, and he gained weight and returned to work. His IRG level has decreased from 2,975 to 200 pg/ml. No side-effects were noted during chemotherapy. Temporary palliation of malignant glucagon-producing neoplasms can be achieved by cytoreductive surgery. When the life-threatening symptoms of this syndrome recur, DTIC chemotherapy seems indicated because of its safety and effectiveness. PMID- 6269243 TI - [Apoplexy and the family doctor (author's transl)]. PMID- 6269244 TI - [Use of cerebral angioscintigraphy in cerebrovascular pathology]. PMID- 6269245 TI - What is the best treatment for early operable small cell carcinoma of the bronchus? PMID- 6269246 TI - Simultaneous occurrence of pulmonary interstitial fibrosis and alveolar cell carcinoma in one family. AB - The coexistence of interstitial pulmonary fibrosis and alveolar cell carcinoma is well known. The familial occurrence of a combination of these two entities, however, is very rare. We present a family of which five members had diffuse interstitial pulmonary fibrosis. Three of them had in addition alveolar cell carcinoma. In a sixth family member, evidence of alveolar cell carcinoma was present without proven interstitial fibrosis. An autosomal dominant trait is suggested as the mode of inheritance of both interstitial fibrosis and alveolar cell carcinoma in this family. PMID- 6269248 TI - Hemophilic bleeding evaluated by blood pool scanning. AB - The technique of blood pool scanning was used to examine 15 hemophilic subjects. Employing an in vivo method for erythrocyte labeling with Technetium-99 m, a dynamic perfusion sequence is obtained using a scintillation camera positioned over the area to be examined. This demonstrates the vascularity of the tissue. Subsequently, equilibrium blood pool images of the area are obtained and analyzed with a densitometer to assess relative regional blood volume. In patients who were not bleeding but had chronic arthropathy, vascularity was not increased, and the blood volume of comparable joints was similar. By contrast, marked increases in vascularity and image density were observed in studies of acutely bleeding joints. Chronic hemarthroses were associated with persistent, but less marked increases in joint perfusion. Transient increases in joint vascularity were demonstrated after insertion of knee prostheses. In a patient with a thigh hematoma, the dimensions of the hemorrhage were clearly delineated. Since only a tracer dose of nuclide is infused intravenously, there are no allergic reactions or other side effects of the procedure. Blood pool scanning is a safe, non invasive technique that augments clinical and radiographic evaluations, and provides a new dimension in the assessment of the hemophilic patient. PMID- 6269247 TI - Arterial plasma histamine levels at rest, and during and after exercise in patients with asthma: effects of terbutaline aerosol. AB - Eight asthmatic patients and two normal subjects performed two identical exercise tests 140 minutes apart (first test preceded by inhalation of saline and the second by terbutaline sulphate). A ninth asthmatic patient exercised twice after placebo 40 minutes apart. Arterial plasma levels of histamine and cyclic AMP, expiratory flow rates and volumes were measured at rest and during and after exercise. After the first test the mean +/- SEM fall in PEFR was 45.2 +/- 2.6%. In five asthmatics there was an increase in plasma histamine (mean +/- SEM 14.8 +/- 3.3 pmol ml-1) coinciding with exercise-induced asthma (EIA). Histamine levels returned to pre-exercise values within 30 minutes. After terbutaline these five patients had histamine levels greater than those observed before, during, or after the first test. This effect may have been the result of changes in pulmonary microcirculation. After the second test the levels decreased indicating no further release of histamine in response to exercise. No EIA occurred in these patients after terbutaline. The other patients and the two normal subjects had little or no change in histamine throughout the study. The one patient in whom exercise was repeated after placebo demonstrated less histamine release and less EIA after the second test. PMID- 6269249 TI - Superoxide, xanthine oxidase and platelet reactions: further studies on mechanisms by which oxidants influence platelets. AB - In the course of studying the effects on platelets of the oxidant species superoxide (O2.-), O2.- was generated by the interaction of xanthine oxidase plus xanthine. Surprisingly, gel-filtered platelets, when exposed to xanthine oxidase in the absence of xanthine substrate, were found to generate superoxide (O2.-), as determined by the reduction of added cytochrome c and by the inhibition of this reduction in the presence of superoxide dismutase. In addition to generating O2.-, the xanthine oxidase-treated platelets display both aggregation and evidence of the release reaction. This xanthine oxidase induced aggregation is not inhibited by the addition of either superoxide dismutase or cytochrome c, suggesting that it is due to either a further metabolite of O2.0, or that O2.- itself exerts no important direct effect on platelet function under these experimental conditions. The ability of C2.- to modulate platelet reactions in vivo or in vitro remains in doubt, and xanthine oxidase is an unsuitable source of O2.- in platelet studies because of its own effects on platelets. PMID- 6269250 TI - [Aujeszky's disease: serological responsiveness after vaccination of 6-10-week old piglets with maternal antibody (author's transl)]. AB - Trials were made to study the extent to which 6-10-week-old piglets with and without virus-neutralizing (VN) antibodies are capable of a serological response to vaccination. The piglets were inoculated with three different vaccines: two live vaccines (Aescovac Aujeszky and MK25 vaccine) and an inactivated vaccine (Geskyvac). The titre of virus-neutralizing antibody in the blood was determined for each vaccine in approximately 200 piglets at the time of inoculation as well as within four and twelve weeks after inoculation. The maternal antibodies present at the time of inoculation were found to have an inhibitory action on the serological response following inoculation. Of those piglets in which a maternal VN titre was observed using the above technique, only 9 per cent showed an increase in titre after inoculation. This proportion was 74 per cent in the serologically negative piglets. Marked variations in serological response to the different vaccines were observed. the most positive response was that induced by Aescovac. There was an obvious relationship between the VN titre following inoculation and immunity against intracerebral challenge with 2,000 TCID50 of Aujeszky disease virus. Animals showing titres of 1:4 or over were immune to this challenge. PMID- 6269251 TI - [Aujeszky's disease: maternal immunity of piglets born of sows inoculated with various vaccines (author's transl)]. AB - Studies on the maternal state of immunity were done in 4-10 week-old piglets born of vaccinated sows free from Aujeszky's disease. The sows were inoculated with three different vaccines: two live vaccines (Aescovac Aujeszky) and the MK25 vaccine) and an inactivated vaccine (Geskyvac). The maternal state of immunity of the piglets was assessed from the titre of the virus-neutralizing (VN) antibodies in the blood. To do so, samples were taken from 300-400 4-10-week-old piglets per vaccine inoculated in the sow. At the same time, the VN titre of the blood of the sow was determined. The VN titres were highest in those sows which were vaccinated with Geskyvac. There was an obvious correlation between the VN titre of the sow and the maternal VN titres of the piglets. As a result, the maternal state of immunity in the sows vaccinated with Geskyvac also was highest. The value of the maternal VN titres in the assessment of maternal immunity was tested by exposing 28-37-day-old piglets showing various maternal VN titres to intracerebral challenge with 2000 TCID50 of Aujeszky disease virus (Van Doorn strain). Piglets showing VN titres higher than 1:8 were usually found to be immune against this challenge. PMID- 6269252 TI - Preparation and analysis of a lung microsomal fraction from control and 3 methylcholanthrene treated rats. AB - In order to facilitate the homogenization of lung tissue it was previously incubated with collagenase during 30 minutes. Morphological observations were performed in order to ascertain the cell integrity. The enzymatically digested tissue was homogenized in a 0.25 M sucrose solution containing 1 mM EDTA, 3 mM imidazole (pH.7.3) and supplemented with 1 mM imipramine in order to stabilize the mitochondria, which otherwise might contaminate the microsomal fraction. The homogenate was then centrifuged and subdivided into four fractions which were analyzed for their content in protein and for the activities of so-called marker enzymes. The cytochrome P450 level was measured in both control and 3 methylcholanthrene preparations. The activities and the kinetic parameters of lung benzpyrene hydroxylase and aldrin epoxidase were measured using the lung microsomal fractions from control and previously 3-methylcholanthrene treated rats; 3-methylcholanthrene pretreatment modified the catalytiac properties of both enzymes. PMID- 6269253 TI - The effect of first-dose doxorubicin on the cyclic nucleotide levels of the human myocardium. PMID- 6269255 TI - Interaction between benzo[a]pyrene and mouse skin in organ culture. AB - An in vitro method for studying the interaction between tritiated benzo[a]pyrene ([3H]BP) and intact mouse skin was investigated. [3H]BP was applied to the epidermal surface of the skin floating on medium, and radioactivity in the medium was measured periodically. After 48-h incubation, about 45% of the radioactivity was in the medium; of this amount, about 80% accumulated during the first 24 h. Incubation temperature, metabolic inhibitors, and the amount of BP applied caused pronounced effects on accumulation; slight to moderate effects were noted for the type and volume of medium and vehicle used. Results of the temperature and inhibitor experiments indicated that accumulation of radioactivity depended on cell viability. About 80% of the radioactivity in the medium was water soluble, showing that biotransformation of BP by skin cells occurred. We are using the skin organ culture method to help understand the interaction of mammalian skin with hydrocarbon mixtures. A study of these interactions may lead to metabolic, cytotoxic, and macromolecular-binding profiles that characterize a carcinogenic mixture of hydrocarbons. PMID- 6269254 TI - The isolated perfused lung--a critical evaluation. AB - Recent refinement and application of the technique of perfusing isolated intact lung preparations from suitable experimental animal has enhanced our knowledge of the non-respiratory functions of the lung. The technique consists of perfusion with whole blood or constituted media via pulmonary artery or artificially ventilated lungs. Such preparations have been known to be especially useful for studies of uptake, metabolism and disposition of exogenous and endogenous substances. Recent advances in unilateral, split-lung perfusion in which left and right lungs are unilaterally perfused simultaneously have enabled investigators to maintain paired controls during perfusion. Such techniques are useful in the study of the interactions of endogenous and exogenous chemicals in the lung tissue. Differences between subcellular or lung slice preparations and intact lung perfusion are to be expected on the basis of distorting natural vascular and extra-vascular barriers in the case of in vitro preparations. Areas in which perfused lungs have not been extensively used include uptake and disposition of gases, solvents and vapors, effects of toxic chemicals on respiratory and non respiratory functions of the lung and alteration of pulmonary mechanisms and hemodynamics in the presence of interacting chemical or physical stimuli. With suitable modifications, application of isolated perfused lung preparations for these investigations should be technically feasible in the future. PMID- 6269256 TI - [Immunity indices in children in herpetic stomatitis foci]. PMID- 6269257 TI - Allotransplantation of insulinoma into the testis of diabetic rats. PMID- 6269258 TI - [Effect of modifying the action of dipin and fotrin in a human lymphocyte culture]. PMID- 6269259 TI - Pyridoxine supplementation during isoniazid therapy. AB - Vitamin B6 (pyridoxine) supplementation during isoniazid (INH) therapy is necessary in some patients to prevent the development of peripheral neuropathy. In vivo pyridoxine is converted into coenzymes which play an essential role in the metabolism of protein, carbohydrates, fatty acids, and several other substances, including brain amines, INH apparently competitively inhibits the action of pyridoxine in these metabolic functions. The reported frequency of INH induced neuropathy in various studies is reviewed and population groups at relatively high risk of developing this complication are identified. The routine use of pyridoxine supplementation to prevent peripheral neuropathy in high risk populations is recommended. PMID- 6269260 TI - The role of whole body scan and skeletal radiography in the preoperative staging of breast cancer. AB - 442 patients with breast cancer were studied by means of radiologic and scintigraphic examination of the skeleton to detect the presence of bone metastases. All the patients have been clinically followed-up for a mean period of 22 months. The overall prevalence of bone metastases at staging was 4.5%. Bone scan showed a higher sensitivity in detecting bone metastases (90% vs 45%) and a lower positive predictive value (60% vs 75%) with respect to X-ray examination. In the presence series no asymptomatic case with bone metastases was found in limited stages (T1-T2 N0-N1). The authors suggest that the bone scan be routinely included in the staging of advanced breast cancer cases and that the use of this procedure be restricted to the symptomatic patients in the more limited stages. PMID- 6269261 TI - [Enzyme immobilization via silochromes, modified by transition metal salts]. AB - The immobilization of pectoawamorine G 10X, pronase E and P, protease from Bac. mesentericus and rat liver microsomal fraction was performed by sylochromes modified by Ti, Zr and Hf salts. The pectinesterase, caseinolytic, esterase and hydroxylating activity of the immobilized preparations, their stability during storage, thermostability and pH optimum are determined. Of greatest interest for practical application are preparations of pectoawamorine. G 10X and pronase E and P immobilized by HfOCl2. PMID- 6269262 TI - [Effect of periodate oxidation on properties of antibodies]. AB - The subject of the present research is the investigation of the influence of sodium periodate on the properties of immunoglobulin G molecules. It is shown that 100 and 300 M of periodate cause a slight enhancement of the sedimentation coefficient which is a result of the higher protein density. However high concentrations (2000 M) of periodate decrease sedimentation coefficient considerably and disturb the protein structure homogeneity. Studies of the immunologic activity in the periodate-treated antibodies by the reaction of passive hemagglutination showed that in low concentrations it did not decrease significantly the activity but with an increase in the concentration up to 2000 M the activity lowered. The conjugation of antibodies with the enzyme markers was fulfilled due to periodate oxidation. The conjugates obtained were successfully used for improving sensitivity of the precipitation line in immunologic tests. PMID- 6269263 TI - [Pivmecillinam (Selexid) in acute cystitis. A comparative study of 3- and 7-day treatments]. PMID- 6269264 TI - [Synovial sarcoma]. PMID- 6269265 TI - [Histochemical investigations on human bladder cancer (author's transl)]. AB - The histochemical enzyme activity of alkaline phosphatase, nonspecific esterase, 5-nucleotidase, beta-glucuronidase, glucose-6-phosphatase, succinate dehydrogenase, and glucose-6-phosphate dehydrogenase in human bladder cancer was investigated. Tumors of 84 patients, classified into grades I-III according to the WHO classification, were compared with 12 normal and 16 inflamed bladder epithelia. As a rule, loss of alkaline phosphatase activity and a decrease of nonspecific esterase activity was found in most of these tumors. The activity of beta-glucuronidase was decreased and compared with normal tissue, also the activity of 5-nucleotidase. The succinate dehydrogenase activity in tumor tissue was frequently increased, whereas glucose-6-phosphate dehydrogenase did not show any significant reaction. PMID- 6269266 TI - [Value of nuclear medicine and ultrasonography in the management of renal trauma (author's transl)]. AB - Intravenous urography remains the most decisive investigative method in the management of blunt renal trauma. Even minor urographical changes would merit scintiscan and ultrasound examination in order to visualize or rule out parenchymal lesions, intra- or extrarenal hematomas and urine extravasation as well as assess respirational excursions of the kidney. Follow-up studies may be performed without hesitation. Major lesions (primarily a urinoma) and alarming clinical findings necessitate further diagnostic procedures (angiography, possibly after computer tomography). In case of a surgical intervention, angiography cannot be replaced by any other diagnostic method to date. There are no comparative studies of patients with similar injuries managed alternatively with immediate operation or a conservative approach. However, based on our diagnostic possibilities and therapeutical results, we are in favor of a more expectant management of major renal trauma. PMID- 6269267 TI - Triamterene stone: advantage of crystallographic analysis. AB - Microscopic crystallographic analysis of renal calculi provides clinically useful information concerning the pathogenesis of stone disease and is, therefore, superior to conventional chemical analysis of stones. The advantages of crystallography, performed at a centralized, experienced stone-analysis center, are highlighted by the recent discovery of triamterene deposits in kidney stones. Deposits of other medications and their metabolites have also been uncovered. Two case reports are presented, the clinical implications of these and related findings are discussed. PMID- 6269268 TI - Treatment of imipramine overdose in children. AB - Enuresis is a common problem often treated effectively with imipramine hydrochloride. The usefulness of this therapy carries with it, however, the risk of accidental overdose by younger siblings of these enuretic patients. Traditional support measures are effective in the treatment of the mild to moderate overdose, while separate symptomatic treatment of seizures and cardiac arrhythmias is possible as outlined herein. Physostigmine offers a single alternate treatment which is effective in the full panorama of life-threatening manifestations of an imipramine overdose. PMID- 6269269 TI - Naloxone and weight reduction: an exercise in introspection. PMID- 6269270 TI - The Jeremiah Metzger Lecture. Myths, mandarins and molecules: the cautionary tale of cholera. PMID- 6269271 TI - Pathology of experimental vitamin D deficiency in chickens and effects of treatment with vitamin D metabolites. AB - Structural changes in bone, parathyroid, and ultimobranchial body were examined in three groups of chicks fed a vitamin D-deficient diet; one group was treated with vitamin D3 and another with 1,25(OH)2D3. Diets were fed from day of hatching until 5 weeks old, when deficient chicks were near death due to hypocalcemic tetany, loss of fat and muscle, and marked bone deformities. In deficient chicks, parathyroid mass increased linearly to 7.5 times normal at 5 weeks. Parathyroid cells were irregular and vacuolated, with few granules. 1,25(OH)2D3 had normal parathyroids until the fifth week, when parathyroid mass increased greatly. There were few differences in length of growth cartilage, but marked changes in length of metaphyses. Deficient chicks had metaphyses nearly five times longer than vitamin D3-treated chicks. Metaphyses in chicks given 1,25(OH)2D3 were twice as long as those of vitamin D-treated chicks at 5 weeks. Both osteoblasts and osteoclasts were more numerous in deficient chicks. These studies suggest that vitamin D3 is more effective than 1,25(OH)2D3 in preventing parathyroid and bone lesions of vitamin D deficiency. PMID- 6269272 TI - Studies of the lung in diabetes mellitus. I. Ultrastructural studies of the lungs in alloxan-induced diabetic rats. PMID- 6269273 TI - Malignant fibrous histiocytoma of bone. Light microscopic and electron microscopic examination of four cases. AB - Malignant fibrous histiocytoma (MFH) of bone is a well-defined tumor by light microscopy but no agreement has been achieved concerning its histogenesis. We present the light and electron microscopic findings of four cases of MFH of bone. In case 1 multiple bone tumors were observed and in case 4 the tumor developed after irradiation. It was our aim to document the cytological variability and to arrange the findings in a histogenetic concept of primary intraosseous MFH. We observed some undifferentiated cells but mainly histiocyte- and fibroblast-like cells including intermediate forms, and several types of giant cells. We should emphasize the fact that there were also some large cells with a light microscopic resemblance to rhabdomyoblasts and with electron microscopic characteristics of myoblastic differentiation. From the ultrastructural point of view, therefore, MFHs seem to derive from a primitive mesenchymal stem cell rather than from the ordinary histiocyte. It is suggested that osteosarcoma and MFH of bone may have a common progenitor cell but it is important to make a clear clinico-pathological distinction between the tumors because of differing biological behavior. PMID- 6269274 TI - Splenic involvement in tuberous sclerosis. Report of three cases. AB - Three cases of tuberous sclerosis in neonates were found to have focal, frequently perivascular, collections of large cells with abundant eosinophilic cytoplasm. These cells resembled those found in brain lesions of tuberous sclerosis but did not stain for acidic protein. Ultrastructurally, they were characterized by many membrane bound cytoplasmic bodies, 90 to 270 nm in diameter, with amorphous contents. Filaments were not demonstrated. Their appearance is considered most consistent with histiocytic origin. Large cells with a histiocytic appearance and a superficial resemblance to those seen in the brain in tuberous sclerosis, but a different ultrastructure and reaction to GFAP staining, may be found in the spleen of neonates with this disease. PMID- 6269275 TI - Cystosarcoma phyllodes of the mammary gland--Muller's tumor. For the 180th birthday of Johannes Muller. AB - For the last 150 years, cystosarcoma phyllodes of the mammary gland has had 62 different synonyms. At the present time, the most logical name for it seems to be tumor phyllodes. The result of the histological analysis of every single tumor should contain information about the degree of its maturity. The classical description of cystosarcoma phyllodes given by Johannes Muller (1838) is still considered the basis for understanding the clinical and histogenetical aspects of this neoplasm. PMID- 6269276 TI - [Experimentally induced herpesvirus SA 8-pneumonia (bronchopneumonia) in Kenya baboons (papio cynocephalus) (author's transl)]. AB - Captive baboons of three age groups were experimentally infected with Herpesvirus SA 8-strain 0430. Intravenous inoculation of the virus induced minor, transient, interstitial pneumonia of a nonspecific type in newborn baboons. Intratracheal inoculation, in contrast, invariably produced multifocal or diffuse necrotizing inclusion body bronchopneumonia within two days in newborn, two months and one year old baboons. Differences in the outcome of the experimental intratracheal infections were noticed, depending on the animals age. All the newborns either died from the extensive pulmonary damage or had to be sacrificed because of serious illness. Older animals, in contrast, survived the initial impact with only minor clinical symptoms and repair of the necrotic and inflammatory lesions. The healing stages were characterized by interstitial fibrosis and transient tumorlike bronchial and bronchiolar epithelial proliferations, which lasted for approximately two months. Intranuclear inclusion bodies in ganglionic cells, ganglioneuritis and neuritis in different parts of the pulmonary plexus in intratracheally infected animals suggested the viral invasion of the pulmonary autonomous nervous system. PMID- 6269277 TI - [Reducing body myopathy--ultrastructure and classification (author's transl)]. AB - Reducing body myopathy is a very rare progressive muscular disease. Apart from a non-specific circumscribed muscle fiber degeneration it displays muscle fiber inclusions which have reducing properties as a typical morphological feature. The nosological classification of the disease is not settled. A case in a 15 years old girl is reported. She suffered from a progressive muscular weakness and atrophy and in a muscle biopsy regressive changes were obvious. Furthermore, multiple eosinophilic muscle fiber inclusions were also observed, which exhibited reducing properties. They consist of electron dense granules with a diameter of 12--16 nm. Since a sister of the patient has suffered for many years from a clinically and morphologically similar muscle disease, reducing body myopathy apparently belongs to the group of congenital myopathies with structural abnormalities. Muscle fiber inclusions with reducing properties also occur in another myopathy, in which they structural and histochemical differ widely from those found in reducing body myopathy. The reducing body myopathy is better named after its typical morphological property, the granular inclusions. It is proposed to name it "granular body myopathy". PMID- 6269278 TI - Malignant fibrous histiocytoma. An electron microscopic study of 17 cases. AB - The ultrastructural findings in 17 cases of malignant fibrous histiocytoma (MFH) are described. The tumors consisted of fibroblast-like cells and histiocyte-like cells in different proportions in different cases. Intermediate, undifferentiated, xanthomatous and multinucleated giant cells were also identified. In 12 of 17 cases myofibroblasts were evident. Acid phosphatase activity was detected cytochemically in the Golgi zone, endoplasmic reticulum and lysosomes (GERL) mainly within histiocyte-like cells, in three cases. These observations indicate that the GERL of the tumor cells are engaged in th formation of lysosomes. The polymorphic cellular composition, including undifferentiated cells, lends support to the concept that the MFH originates from a primitive multipotent undifferentiated mesenchymal cell. PMID- 6269279 TI - Effects of reserpine treatment on beta-adrenergic/adenylate cyclase modulate secretion and resynthesis by the rat submandibular gland. AB - Chronic reserpine (adrenergic blocking) treatment causes a marked accumulation of secretory protein in the rat submandibular gland (SMG) but discharge of this material is delayed in response to isoproterenol stimulation. The purposes of this study were to investigate the effects of chronic reserpine treatment on 1) the number of beta-adrenergic receptor. 2) the sensitivity of cell-surface associated adenylate cyclase to various concentrations of isoproterenol, and 3) to correlate these data to morphologic studies of the secretion and resynthesis phases of the isoproterenol-induced secretory cycle in the rat SMG. Animals were injected with reserpine (0.5 microgram/g b.w.) for 6 days. Plasma membrane fractions were prepared. The adenylate cyclase response to a series of isoproterenol concentrations, and the number of beta-adrenergic receptors ([3H] alprenolol binding) were determined. Other animals were given a single dose of isoproterenol (0.8 mg/100 g b.w.) and the SMG was examined by light and electron microscopy at various times (30 min to 24 h) after treatment. Chronic reserpine treatment leads to a 2.5-fold increase in SMG beta-adrenergic binding sites and a 50-fold increase in adenylate cyclase sensitivity to IPR stimulation when compared to controls. However, secretion and resynthesis of secretory product in response to IPR stimulation was greatly delayed in reserpinized rats. PMID- 6269280 TI - Synthesis of virus-specific proteins in simian sarcoma virus-transformed primate cells. PMID- 6269282 TI - Analysis of the nonviral antigens immunoprecipitable by SV40 T antibody from SV40 transformed human/mouse hybrid cell lines. PMID- 6269281 TI - Clonal isolate of the simian sarcoma virus codes for a Gag-related 65,000-dalton protein. PMID- 6269283 TI - Isolation and characterization of a new mouse mammary tumor virus from BALB/c mice. PMID- 6269284 TI - Analyses of the genomes of bluetongue viruses recovered in the United States. I. Oligonucleotide fingerprint studies that indicate the existence of naturally occurring reassortant BTV isolates. PMID- 6269285 TI - Human cytomegalovirus DNA: restriction enzyme cleavage maps and map locations for immediate-early, early, and late RNAs. PMID- 6269286 TI - New Anabaena and Nostoc cyanophages from sewage settling ponds. PMID- 6269287 TI - Selective inhibition of cellular protein synthesis by amphotericin B in EMC virus infected cells. PMID- 6269288 TI - Infection of escherichia coli K-12 by bacteriophage phi X-174. PMID- 6269289 TI - Four Rous sarcoma virus mutants which affect transformed cell morphology exhibit altered src gene products. PMID- 6269290 TI - Immunoprecipitation of Marek's disease virus-specific polypeptides with chicken antibodies purified by affinity chromatography. PMID- 6269291 TI - Nucleic acid homology between avian and mammalian type C viruses: relatedness of reticuloendotheliosis virus cdna to cloned proviral DNA of the endogenous Colobus virus CPC-1. PMID- 6269292 TI - Mechanism of inhibition of Epstein-Barr virus replication by phosphonoformic acid. PMID- 6269293 TI - Analysis of endogenous avian retrovirus DNA and RNA: viral and cellular determinants of retrovirus gene expression. PMID- 6269294 TI - Bovine rotavirus-cell interactions: effect of virus infection on cellular integrity and macromolecular synthesis. PMID- 6269295 TI - [Occurrence of lipoid pneumonia in patients with bronchiolar-alveolar carcinoma]. PMID- 6269296 TI - [Alteration in activities of NAD-glycohydrolase, acid and alkaline phosphatases in blood cells tuberculosis]. AB - Activities of NAD-glyconydrolase from erythrocytes, alkaline and acid phosphatases from neutrophiles and acid phosphatase from lymphocytes were studied in patients with pulmonary tuberculosis as well as in experimental animals. Distinct alterations in the activity of the enzymes studied were observed in blood cells of guinea pigs inoculated with tuberculosis. In patients with active pulmonary tuberculosis activities of acid and alkaline phosphatases were altered in leukocytes and the activity of NAD-glycohydrolase--in erythrocytes. Inactive forms of tuberculosis were accompanied by a slight alterations in the alkaline phosphatase activity, activities of acid phosphatase and NAD-glycohydrolase were unaltered. PMID- 6269297 TI - [Content of cyclic nucleotides in blood plasma of patients with bronchial asthma]. AB - The ratio of cAMP and cGMP in blood plasma of patients with bronchial asthma was altered depending on the severity of the disease. There was noted a decrease in cAMP content and an increase--in cGMP. Distinct alterations in the cAMP content were not observed in infectious and atopic forms of the asthma. Content of cGMP was higher in blood plasma of patients with infectious form of the asthma as compared with the atopic one. Dynamics of improvement in the patients with the severe type of bronchial asthma was accompanied by the increased in the ratio cAMP/cGMP due to an increase in the cAMP content, while the content of cGMP remained elevated. PMID- 6269298 TI - [Susceptibility of rat thymocyte subpopulations to thymosine affecting their protein synthesis and dexamethasone receptors]. AB - Protein synthesis and reception for 1,2-3H-(N)-dexamethasone were studied in A, B, C, D subpopulations of rat thymocytes after treatment with thymosine, cyclic adenosine-3,' 5'-monophosphate (cAMP) and caffeine. Thymosine inhibited the 1,2 3H-(N)-dexamethasone reception in rat thymocyte subpopulations A, B and C by 30 40%, stimulated the protein synthesis in A and B fractions by 30% as well as inhibited the synthesis in D fraction by 14%. Caffeine, administered together with thymosine, inhibited the protein synthesis by 80% in C and D thymocyte subpopulations and - by 47% in B subpopulations. After simultaneous treatment with exogenous cAMP, thymosine and caffeine the protein synthesis was inhibited by 14% in all the thymocyte subpopulations. The data obtained suggest that thymosine and caffeine affect the various lymphocyte T subpopulations, dissimilar in their differentiation. PMID- 6269299 TI - [Basic ultrastructural cell types of human cancerous breast tumors]. AB - Five main types are distinguished among differentiated (1st Group) and undifferentiated (2nd Group) cells of breast tumor. First Group includes types I, II and III of cells, while the 2nd Group-types IV and V. Type I has organ specific features and a cytoplasm rich in organelles. Type II is characterized by organ-specific features and a cytoplasm. with a small amount of organelles. Type III is represented by myoepithelial cells. The cancer cells of the 2nd Group do not contain organ-specific features but they can be rich (type IV) or poor (type V) in organelles. All live types of cells can have the features of epithelial tissue and can be "light" or "dark". Such typing of cancer cells facilitates the differential diagnosis of breast carcinoma. PMID- 6269300 TI - [Determination of leukocyte sensitization to tumor and embryonic tissue antigens in cancer of the large intestine]. AB - Aqueous-saline extracts of autologous rectal tumor tissue inhibited leukocyte migration in 7 out of 10 patients with rectal tumors in autoplasm-containing medium, and in 5 out of 11 patients-in control serum. Antigens of allogenic rectal tumors inhibited leukocyte migration (LMI) in 4 out of 5 patients (stage II), in 15 out of 21 patients (stage III), and in 5 out of 10 patients (stage IV) in control serum medium, and in non of control patients. Leukocyte sensitization to mucosal antigen was established only in 8% of patients (stage II-IV), in control serum medium. LMI in medium containing autoplasm and control serum was observed in 24 out of 36 patients. Extracts obtained from human embryonal liver inhibited leukocyte migration in 14 out of 27 patients (stage II-IV), including 3 cases in which leukocytes did not respond to tumor-associated antigen. LMI by carcinoembryonic antigen was registered in a total of 31 out of 36 cases (86%). In 5 cases out of 7, unresponsive leukocytes of patients with rectal tumors did respond to tumor-associated antigen by inhibiting leukocyte migration, after re incubation at low temperature, in a medium free from autologous blood plasma. PMID- 6269301 TI - [Determination of after care periods for cancer patients]. AB - Following an analysis of case histories of in-patients treated for tumors of the stomach and cervix uteri at the clinics of the Center in 1979, an assessment of the work put in by the personnel at different stages of their treatment and on the basis of interviews with the clinics' chiefs it was found that the establishment of an optimal period of postoperative treatment of tumor in patients is impracticable. Due to a high degree of tumor specialization and a wide range of tumor sites, the establishment of specialized clinics or hospitals may face additional difficulty in selecting admissions and running wards with variable turnover of in-patients and highly-specialized personnel. PMID- 6269302 TI - [Indices of the strength of collective pertussis immunity]. PMID- 6269303 TI - [Treatment effectiveness in peripheral nervous system diseases at an intercollective farm preventorium]. PMID- 6269304 TI - Juvenile nasopharyngeal angiofibromas. PMID- 6269305 TI - [Therapy with corticosteroids]. PMID- 6269306 TI - [Experiences with low-dose insulin therapy in diabetic precoma/coma in basic hospital care]. PMID- 6269307 TI - [Problems of curative prostatic cancer therapy]. PMID- 6269308 TI - [Clinical value of N-acetyl-beta-D-glucosaminidase and alpha-galactosidase in liver diseases]. AB - N-acetyl-beta-D-glucosaminidase is a lysosomal glycosidase, which participates in the catabolism of the mucopolysaccharides and of the glycoproteins. For the determination of this enzyme the production of the substrate and a modified methodology are described. Measurements of the activity were performed by 4 nitrophenyl-alpha-D-galactopyranoside and 4-nitrophenyl-N-acetyl-beta-D glucosaminide as substrates. Examinations of this enzyme were performed in patients with acute virus hepatitis, chronic hepatitis, liver cirrhosis and healthy test persons. In acute hepatitis and liver cirrhosis and significant increase of enzyme is provable, but not in protracted hepatitis. PMID- 6269309 TI - The microscopical structure and quantitative changes of pituitary cell populations in frogs (Rana esculenta L.) irradiated by ultraviolet light. AB - The percentage of cell populations of hypophysis pars distalis, their ultrastructure, degranulation phenomena and volume of cell nuclei easured by karyometry was examined in frogs, Rana esculenta L. irradiated by UV light. The observed changes, reflecting alterations of the secretory activity were most prominent in B2 cells producing gonadotropic hormones and in B3 cells probably responsible for the secretion of ACTH. A concomitant increase of the number of chromophobic cells was observed. The obtained results are discussed in relation to data from the existing literature. PMID- 6269310 TI - [The effect of active substances on nerve fiber regeneration in nerve tissue cultures]. AB - Explants of the ganglion trigeminale from chick embryos and hippocampi from embryonal rats were incubated in maximowchambers with semisynthetic media. The different parts of nervous tissue were influenced experimentally by addition of biological extracts and by substances with known composition. The regeneration of nerve fibers was investigated by the index of growth. The growth index was calculated from the ratio of nerve fibre index of the test cultures to that of the influenced cultures. Under these conditions biological extracts enhanced the growth of nerve fibres. In the same way the growth of nerve fibres was statistically significantly stimulated by substances with known composition of aminoacids, orotic acid, sodium orotate and cyclic monophosphates. A stimulating effect of cyclic guanosinmonophosphate seems to exist only in CNS explants and only in young fetal rats and consists in an increased migration and proliferation of cells as well as in the formation of fibres from neuroblasts. The investigations gave strong evidence for the in vitro testing to be very useful in studies of nerve fibre regeneration. However the choice of suitable reference systems, suitable quantitative parameters, optimal concentration and periods of application of effective substances and the age of the animals are of fundamental importance for the evaluation of the results. Experiments regarding the stimulation of the differentiation of neurons and the growth of nerve fibres are of practical clinical and therapeutical interest. PMID- 6269311 TI - [Evidence of the recycling of vesicle membranes by means of morphometric measurement of the vesicle density (author's transl)]. AB - Quantitative-electron microscopic investigations have been performed on large morphologically mixed synapses in the oculomotor nucleus of the trout with the aim to get some hints at recycling processes of vesicle membranes. For this reason vesicle density of the presynaptic area and number of vesicle attachment sites of the presynaptic membrane of the active zones within these mixed contacts have been estimated in two different experimental groups. Furthermore, vesicle density near the unmyelinated axolemma of the axon terminal has been measured in both groups. The results obtained support the view that a recycling of vesicle membranes occurs in morphologically mixed synapses, probably also over the axolemma of the so-called extended extracellular spaces, which are interrupting the contact area between the two neuronal elements. The question of a recycling of gap-junction-vesicles has not been answered. PMID- 6269312 TI - [Ultrastructural modifications in the hypophyseal-adrenocortical system in rabbits during experimentally induced parodontosis (author's transl)]. AB - During parodontosis induced experimentally by irritation of dental pulp with carbolic acid in rabbits, the participation in the pathological process of adenohypophyseal ACTH-producing cells and of adrenocortical fasciculata cells was studied. Ultrastructural alterations suggesting stimulation of ACTH and glycocorticoid synthesis were observed. The data obtained prove that via afferent pathways to the central nervous system, irritation of the dental pulp induces morphofunctional alterations in the hypothalamo-adenohypophyseal neurosecretory system, by means of functional perturbation of the cerebral cortex leads to hypothalamus (CRF) leads to adenohypophysis (ACTH) leads to adrenal cortex (glucocorticoids)axis. PMID- 6269313 TI - Protein kinases in HeLa cells and in human cervix carcinoma. AB - Extracts of HeLa cell fractions were analyzed by DEAE- and phospho-cellulose chromatography for their range of cyclic AMP-dependent and -independent protein kinase activities phosphorylating histone and/or phosvitin; extractions were by phosphate buffered saline (soluble protein kinases) and the non-ionic detergent NP-40 (membrane-bound protein kinases). The soluble fraction contained (i) cyclic AMP-dependent histone kinases type I and II as evidenced by their behaviour on DEAE-cellulose and inhibition by specific heat- and acid-stable protein kinase inhibitor (PKI) in a dose-related manner; both types I and II as well as their purified catalytic subunit also phosphorylated protamine and - with very low efficiency - casein but not phosvitin; (ii) a histone kinase (H), insensitive to cyclic AMP and PKI, also accepting protamine as substrate but not either casein or phosvitin; (iii) a phosvitin kinase (P), insensitive to cyclic AMP and PKI, which also phosphorylates casein but not histone or protamine. These four enzyme species were also found in NP-40 extracts of 27000 x g residues which, however, contained further histone and phosvitin kinase activities as yet unspecified. NP 40 extracts of the microsomal fraction possessed, besides unspecified histone and phosvitin kinase activity, only the phosvitin kinase P and appeared to be devoid of histone kinases I, II, and H. The occurrence and ratios of the protein kinases classified suggest an ordered distribution over the diverse subcellular fractions of HeLa cells. The overall pattern of soluble and membrane-bound histone and phosvitin kinases in extracts of cervix carcinoma tissue, the in vivo correlate of HeLa cells, closely resembled that of similar extracts of HeLa cells. HeLa cells hence appear, despite their long in vitro history, to express protein kinase activities similar to those of their in vivo ancestors, recommending them as a subject for the study of (certain) human protein kinase systems. PMID- 6269314 TI - Interaction of phloretin with the human red cell membrane and membrane lipids: evidence from infrared, Raman and ESR spectroscopy. AB - The transport inhibitor phloretin was bound to human red cell membrane and the concomitant structural changes were observed by spectroscopic methods. By the spin labeling method a decrease in fluidity of the membrane was found at 1 and 10 microM concentrations of the reagent. This result was obtained with the 2-(3 Carboxypropyl)-4,4-dimethyl-2-tridecyl-3-oxazolidinyloxyl, and the 2-4(14 Carboxytetradecyl)-2-ethyl-4,4-dimethyl-3-oxazolidinyloxyl lipid spin labels. Infrared spectroscopy of modified membranes revealed an intensity increase of the POO- band at about 1250 cm-1. Moreover, a shift of the peak at 1050 cm-1 to 1100 cm-1 was observed in the presence of phloretin. Raman spectroscopy of the membranes did not contradict the results found with infrared and ESR spectroscopy: In the phloretin modified membrane we observed a lack of the band at 1085 cm-1, which leads to suggest that the POO- and/or C-C regions are less fluid. Changes of the extracted red cell membrane lipids were less characteristic, and the results differed from those found in red cell membrane. PMID- 6269315 TI - [Multineuronal analysis of the systems function of cortical cells]. PMID- 6269316 TI - [Development of highly sensitive methods of detecting antibodies to structural proteins of bovine leukemia virus]. PMID- 6269317 TI - [Changes in the functional state of immunocompetent cells and the central nervous system in the early stages of immune response development]. PMID- 6269318 TI - [Topical diagnosis in hypoglycemia. Possibilities and value]. PMID- 6269319 TI - [Receptor-ligand reaction in the central nervous system (principal problems and prospects for development)]. PMID- 6269320 TI - [Effect of diazepam on cyclic changes in the excitability and status of Na, K ATPase in an epileptic focus]. PMID- 6269321 TI - [Soviet corticotropin in the treatment of neurodermatitis and eczema]. PMID- 6269322 TI - [Mollusk neuron habituation following extra- and intracellular administration of an ACTH fragment]. AB - By means of intracellular recording of the mollusc neuronal activity a study was made of the influence of ACTH4-7--a fragment of the stress hormone,--on elaboration of habituation to tactile stimuli. ACTH was administered immediately after the elaboration of the series I of habituation (25 to 30 stimuli) by means of either perfusion or extra- or intracellular microionophoresis. This was followed by the II-V habituation series (with 15 min intervals between them). Perfusion and extracellular (not intracellular) ACTH4-7 administration produced an acceleration of habituation in the series II, increase of action potentials (AP) thresholds in the response to the first tactile stimulus of series II and cessation of further increase of the AP thresholds in the course of elaboration. Without ACTH, these phenomena were observed beginning with habituation series IV. The ACTH action while influencing the memory is apparently directed to the external side of the excitable neuronal membrane; ACTH seems to accelerate the consolidation process. Any of the methods of ACTH administration produced also an enhancement of EPSPs and an increase in the number of APs in the responses to stimuli, without lowering the thresholds of APs generation. This testifies toi enhanced chemosensitivity of the membrane and may underlie the influence of ACTH on the level of wakefulness. PMID- 6269323 TI - [Age and sex differences in the elaboration and maintenance of conditioned taste aversion in rats]. PMID- 6269324 TI - [Syndactylism of the hand. Pathogenetic and therapeutic aspects (author's transl)]. AB - The latest concepts of the genetics of isolated syndactyly are described in relation to a case in which the malformation could be traced back to four generations. The different principles of classification of syndactyly and the therapeutic possibilities are discussed, calling special attention to early operation in infants. PMID- 6269325 TI - [Glucosteroid activity in hyperthermia: an investigation of thermotherapy in rheumatology]. PMID- 6269327 TI - [Structural variability of malignant fibrous histiocytomas of soft tissue. Light microscopical and histochemical observations on three atypical cases with a long lasting follow-up period (author's transl)]. PMID- 6269326 TI - [Profilographic studies with 99mTc-pertechnetate in joint diseases in children]. AB - The inflammatory activity of joints can be stated after intravenous administration of 99mTc-pertechnetate by demonstration of an enrichment of isotope. In 85 out of 111 patients (77%) a good accordance between profilogram and clinical finding could be seen. "False positive" results could be found in juvenile rheumatoid arthritis, ulcerative colitis, reactive arthritis and juvenile gout. In some cases of juvenile rheumatoid arthritis the clinical finding is later obvious than the demonstration by nuclear medicine. "False negative" results mainly can be seen at the wrists of patients with juvenile rheumatoid arthritis and tendosynovitis as well as in already existing radiological changes of the bones. Differential diagnostical evidences of profilography cannot be expected with the investigation technique used here. It, however, may contribute to assure the diagnosis in non-inflammatory joint diseases ("psychogenic rheumatism", lymphatic oedema). PMID- 6269328 TI - [Developmental and current status of clinical liver transplantation]. AB - Liver transplantation is gradually beginning to move from the experimental to the clinical stage. Of the approx. 340 human "transplantation" which have been carried out worldwide, approx. 250 were performed by the transplantation teams in Denver and Cambridge. They were performed orthotopically. The detailed analysis of the indications by Calne ( n = 81) and Starzl (n = 153) is supplemented by analysis of the course of a total of 223 cases. Individual cases, such as a child with a liver transplant which is functioning for 9 1/2 years, show that liver transplantation is possible. Statistically, however, liver transplantation still involves a big question mark. Nevertheless, the Denver team has announced a 1 year survival quota of almost 50%. In the statistics on the causes of death, technical complications are clearly on the decline. The biliodigestive anastomosis constituted a "locus minoris resistentae", recently, however, the complication rate has been lowered considerably by the use of a Roux-Y-loop bypass and an intermediate gallbladder conduit. Infectious complications - bacterial, fungal and viral - caused or at least promoted by immunosuppression are a main problem. The special immunologic situation of the liver in transplantation has as yet not been clarified either experimentally or clinically. Unequivocal evidence of graft rejection is often difficult, because infectious and drug-induced liver intoxications can produce similar symptoms. PMID- 6269329 TI - [Epidemiology of nosocomial clostridial myonecrosis (gas gangrene) (author's transl)]. AB - The occurence of Clostridium perfringens in the environment of different hospital wards and on the skin and in the faeces of in-hospital patients was examined. The author holds the view that most cases of manifest gas gangrene are caused by autogenous infection and not coming from outside. PMID- 6269330 TI - [Hygienic problems at the winning of peloids (peats and sludges of lakes) for balneological therapy (author's transl)]. AB - In Austria there exist no regulations for the quality of peats and sludges of lakes for the external usage in balneotherapy. The results of our examinations showed that peats on the whole (Fig. 1) have much better bacteriological results than sludges of shallow, eutrophic lakes (Fig. 2). Typical intestinal germs appeared only in one of the five examined peats during a rain period down to 0.6 m beneath the surface. Three of the peats showed satisfying local and bacteriological conditions, one of the peats had a critical hygienic topography and high bacterial counts were found. The outcome of the bacteriological examinations of the three sludge-samples of two lakes showed quite a worse result. High levels of intestinal bacteria, E. coli, Enterococci, C. perfringens, were detectable. The averages of the bacterial counts of the peats and the sludges of lakes over the whole drilling length shows Fig. 3. The results of our examinations demonstrate that in most cases peats far away from human settlements may be used under appropriate conditions. To the contrary sludges of shallow, eutrophic lakes are not usable for balneological therapy because of the massive contamination with intestinal germs. There obviously is a danger for the patients to catch an illness when being treated with such sludges. Criteria for the bacteriological status of peloids are set up for discussion and the minimal quality demanded is that 1 g of peloid has to be free of intestinal bacteria. PMID- 6269331 TI - Partial analysis of the polypeptide composition of a porcine lymphoma C-type particle (PLCP). PMID- 6269332 TI - Differences in reaction behaviour of structural polypeptides of bovine viral diarrhoea virus (BVDV) with antisera against BVDV and hog cholera virus (HCV). PMID- 6269333 TI - A note on assessment of post-challenge viraemia as an index of protective immunity in pigs against foot-and-mouth disease. PMID- 6269334 TI - [Effect of mutations imparting resistance to antibiotics having different mechanisms of action on the virulence of Shigella flexneri]. AB - The study of the interaction between mutants of Sh. flexneri 2a and epithelial HeLa cells has revealed that in all cases the loss of virulence in the studied groups of mutants, resistant to antibiotics with different mechanisms of action (polymyxin M, mecillinam and neamin) was linked with the loss of the ability of bacteria to penetrate into epithelial cells. These changes are probably the result of disturbances in the structure of external membrane in polymyxin resistant mutants, in the regulation of the penetration factor synthesis in mecillinam-resistant mutants, and in the translation process in neamin-resistant mutants. PMID- 6269335 TI - The effect of adrenocorticotropic hormone (ACTH) on embryonic chicken gonads. AB - Chicken embryos were exposed to a single dose of adrenocorticotropic hormone (ACTH) on the 15th day of the incubation period. Five days later, the female embryos showed a significant increase in ovarian weight, ovarian thickness and oocyte count. In contrast, the male embryos showed a significant decreased in testicle weight, seminiferous cord diameter and gonocyte number. The opposite response of testes and ovaries is discussed. PMID- 6269336 TI - Restriction of PM2 supercoiled DNA by Hap II endonuclease. AB - Restriction of the covalently closed circular DNA from phage PM2 (CCC PM2 DNA) by Hap II endonuclease was studied under varying enzyme concentration. At low Hap II concentration, accumulation of the intermediate product, OC DNA, was observed at the early stages of the reaction. The resulting final mixture of restriction products consists of OC and L DNA, and their relative content depends on the concentration of the enzyme used. The affinity of the enzyme for the intact recognition site of the substrate in different conformational forms does not seem to be affected. Basically identical results were obtained with the two different CCC DNA used: PM2 and SV40 DNA. PMID- 6269337 TI - On the role of cyclic AMP-independent protein kinases in the modification of yeast ribosomal proteins in vivo. AB - Two proteins of yeast 40S ribosome subunit and four proteins of the 60S ribosome subunit were labelled in vivo with [32P]orthophosphate. Five of these proteins were phosphorylated by protein kinase 3, an enzyme which is cyclic AMP independent and uses ATP and GTP as phosphoryl donors. Two proteins, belonging to the 60S ribosome subunit were phosphorylated by another, highly specific, cyclic AMP-independent protein kinase 1 B. Both in vivo and in vitro the most extensively phosphorylated protein species were acidic proteins, L44, L45 (according to the nomenclature of Kruiswijk & Planta, Molec. Biol. Rep., 1, 409 415, 1974) possibly corresponding to bacterial L7 and L12 proteins. The 40S ribosomal protein, S9, analogous to mammalian S6 protein, was phosphorylated in vivo but was not phosphorylated in vitro by either of the cyclic AMP-independent protein kinases. The obtained results clearly indicate that cyclic AMP independent yeast protein kinases might be involved in the modification in vivo of some ribosomal proteins, in particular of the strongly acidic proteins of 60S ribosome subunit. PMID- 6269338 TI - Metabolism of 7,12-dimethylbenz[a]anthracene by isolated and cultured cells from rat adrenals. PMID- 6269339 TI - Repriming of the delayed potassium channel in frog skeletal muscle. PMID- 6269340 TI - Cytodiagnosis of gastric carcinoma, linitis plastica type (diffuse, infiltrating, poorly differentiated adenocarcinoma). AB - Two hundred seventy cases, with a total of 359 gastric samples, were reviewed. Fifteen cases of linitis plastica (diffuse, infiltrating, poorly differentiated adenocarcinoma) and 25 cases of other types of gastric cancer were identified. Four false-negative cases in the limits plastica group and nine false positives in the other group were studied. The sensitivity of cytologic evaluation in limits plastica was 73.3% and in other groups was 98%. Predictive value of positive results in linitis plastica was 100% but in the other group was 72.7%. The reasons for these findings are discussed. PMID- 6269341 TI - Ten years of respiratory cytopathology at Duke University Medical Center. II. The cytopathologic diagnosis of lung cancer during the years 1970 to 1974, with a comparison between cytopathology and histopathology in the typing of lung cancer. AB - In 1975 Duke University Medical Center, a retrospective and prospective survey of respiratory cytopathologic specimens was undertaken for the ten-year period 1970 to 1979. The purpose of this study was to document the role of cytopathology in the diagnosis of lung cancer at this institution. This paper presents the results of the cytopathologic and histopathologic typing of cases of lung cancer seen at Duke University Medical Center from 1970 to 1974. During this period, 9,892 cytologic specimens from the lower respiratory tract were processed. Cytopathologic diagnoses of cancer with tissue confirmation were made on 483 specimens from 232 patients. Because original cytologic diagnoses, but not histopathologic diagnoses, had been made in conformity with a modified WHO classification of lung neoplasms, all histopathologic material was reviewed and reclassified when necessary. This was carried out by one of the authors (E.H.B.) as a blind review without benefit of knowledge of either preexisting cytopathologic or histopathologic diagnoses. Twenty-six patients were excluded from the current study because of lack of satisfactory histologic material. In 94 patients classified by histopathology as having squamous cell carcinoma, 76.4% of the positive cytologic specimens were also called squamous cell carcinoma; 18.6% were interpreted as large cell undifferentiated carcinoma. In 39 patients classified by tissue as having large cell undifferentiated carcinoma, the cytology agreed in 42.4% of the positive specimens. For the 29 patients thought histologically to have small cell undifferentiated carcinoma, the same diagnosis was rendered in 95.5% of the cytologically positive specimens from these patients. For the adenocarcinoma group of 43 patients, a cytopathologic diagnosis of adenocarcinoma was made in 67.8% of the positive specimens. PMID- 6269342 TI - Scanning electron microscopy of alcohol-fixed cytopathology specimens. AB - Cells in specimens fixed in alcohol and stained by the Papanicolaou method for routine cytodiagnosis were subsequently studied by scanning electron microscopy (SEM) to determine if they manifested topologic features described in specimens prepared for optimal SEM observation. In normal bronchial washings, ciliated columnar cells were obvious, and microridges were detected in several squamous cells. Microvilli, although sometimes coarse and blunted, were present in cells of adenocarcinoma, squamous carcinoma and malignant mesothelioma in fluid specimens. Benign histiocytes in bronchial washings, neuroblastoma cells in a smear of bone marrow aspirate and lymphocytic lymphoma cells in spinal fluid had ruffled surfaces. Should topologic features prove to be diagnostically significant, SEM may be of value in further studying equivocal specimens even though they were previously prepared for routine light microscopic observation. PMID- 6269343 TI - Characterization of triton-solubilized TSH receptors from human thyroid plasma membranes. AB - The TSH receptor from human thyroid plasma membranes has been solubilized in 10 mM Tris/HCl, 50 mM NaCl, pH 7.4 containing 0.5% triton X-100. Binding of [125I]TSH to the soluble receptor showed rapid and reversible kinetics and reached a maximum within 30 min at 37 degrees C, by 1 h at 25 degrees C and by 24 h 4 degrees C. Optimal pH was 7.4. The soluble receptor retained specificity with cross-reactivity only to crude hCG (0.03%). Scatchard plots were curvilinear indicating the presence of at least two binding sites. The high affinity site showed an affinity content of 1.1 X 10(9) M-1 with binding capacity of 1.3 X 10( 10) M/mg protein. TSH-binding inhibitor immunoglobulins from patients with Graves' disease inhibited [125I]TSH binding to the soluble receptor in a dose dependent manner. NaCl inhibited the TSh binding and this was ascribed to the decrease in the receptor capacity. Trypsin, neuraminidase and phospholipase C treatment of the solubilized receptor had no effect on TSH binding. The apparent molecular weight of the receptor, determined by gel filtration of Sepharose 6B, was approximately 300 000. PMID- 6269344 TI - Changes in the cyclic nucleotides (cCMP, cAMP, and cGMP) of rat thyroid induced by prolonged administration of LATS and TSH. PMID- 6269345 TI - Effect of thiol blocking agents on the binding of T3 and T4 in rat liver nuclear extract. AB - Liver nuclei bind thyroid hormones (T3 and T4) with different binding affinities. In out studies it was estimated that the apparent association constant (Ka) in the liver nuclei for T3 was 8.8 X 10(10) l mol-1 and for T4 was 4.1 X 10(9) l mol 1. We have found that the binding sites for T4 are also saturated by an excess of unlabelled T4 and that saturation was dependent on the purification step of liver binding proteins. In liver nuclear extracts with 0.4 mol l-1 KCl the specific binding of T3 and T4 was blocked with a typical -SH blocking agent N ethylmaleinimide (NEM) and by new types of -SH blocking agents such as p bromphenylisothiocyanate (p-BPI) and 2,3 dicyano-1,4-dithio-9,10 antrachinone (Delan). NEM and p-BPI increased the non-specific binding of T4 and completely abolished specific binding. All these agents blocked the specific binding of T3. These results demonstrate that T3 and T4 binding sites in the liver nuclei may not be altogether identical and that the different effects of -SH blocking agents on the binding of T3 and T4 is probably associated with the structural configuration of these drugs. PMID- 6269346 TI - Purification and some properties of polynucleotide kinase from rat liver nuclei. AB - Polynucleotide kinase was purified from crude extracts of rat liver nuclei by affinity chromatography on DNA agarose. At optimal pH (5.5) and at saturating concentrations of ATP and DNA, the purified enzyme was found to express maximal activity in the presence of 0.10-0.15 M NaCl; higher salt concentrations inhibited the activity. At the optimal pH and NaCl concentration, the apparent KM for 5'-OH-DNA at 100 microM ATP was 46.2 microM and the apparent KM for ATP at 1 mM 5'-OH-DNA was 15.8 microM. Polynucleotide kinase was protected against heat inactivation by ATP as well as by 5'-OH-DNA at low and moderately high NaCl concentrations, which suggests that under these conditions the enzyme reacts according to a random reaction mechanism. Studies on the heat inactivation of the enzyme in the presence of 5'-OH- or 5'-P-DNA revealed the protection occurs only if 5'-OH-DNA is present, at NaCl concentrations permitting the enzyme to bind DNA. PMID- 6269347 TI - Receptor amplifying effect of serotonin and serotonin analogues in a protozoan (Tetrahymena) model system. AB - A 72-hour treatment of Tetrahymena with serotonin analogues at a concentration of 10(-9) mmole/l resulted in a decrease of the reproduction rate, whereas serotonin itself was ineffective. On the second exposure to antagonists, cellular division was enhanced but its rate remained around or below the control value, while the second exposure to serotonin produced a more marked effect than the first one did, which finding implies a receptor amplification. The most pronounced receptor amplification was caused by the first exposure to serotonin. This observation indicates that the receptor is rather selective as regards the amplification effect. PMID- 6269348 TI - Dose dependence of the thyrotropin (TSH) receptor damaging effect of gonadotropin in the newborn rats. AB - A single gonadotropin treatment of newborn rats influenced the thyrotropin (TSH) provoked thyroxine (T4) production of 2 months old animals. On pretreatment with 10, 20, 50, 100 and 200 I.U. of gonadotropin, the T4 blood level of animals given 10 and 200 I.U. differed scarcely from the controls treated only by TSH, while intermediary doses had a damaging effect as the T4 values were well below the control values measured in animals treated by TSH in adulthood. PMID- 6269349 TI - The role of membrane processes in controlling skeletal muscle function. AB - The role of membrane processes in the activation of skeletal muscle fibers has been investigated in details recently. It seems very probable that the intramembrane charge movement is the potential sensitive step of the excitation contraction coupling. Considerable efforts were made to monitor the subsequent steps (SR function, Ca release) using optical methods. Experimental data were presented about the relations existing between charge movement process, Ca release and contraction threshold. PMID- 6269351 TI - In vitro inhibition of cyclic 3' 5',-AMP-phosphodiesterase by a group of structural analogues of glaucine. AB - Both glaucine and six of its structural analogues applied in increasing concentrations produced a concentration-dependent inhibiton of cyclic 3' 5'-AMP phosphodiesterase in homogenates from different organs of guinea-pigs and rats. At one and the same concentration of the compound tested the percentage of inhibition varied within wide ranges depending on the compound used, as well as on the organ and on the Km of phosphodiesterase. The changes in the chemical structure of glaucine and the changes in the inhibitory effects on phosphodiesterase activity of tissue homogenates were compared. Some of the compounds applied in appropriate concentrations showed a twice higher inhibitory activity than glaucine. This finding is of particular importance having the mind the much lower toxicity of these compounds compared with glaucine. Essential differences in the dynamics of the concentration-dependent phosphodiesterase inhibition between the compounds were established. The observed peculiarities of the inhibitory effects of the compounds tested favour the concept of the multiple nature of phosphodiesterase. The data from the pharmacological investigation on glaucine and its semisynthetic analogues led us to believe that the effect of 2 compound on phosphodiesterase activity of homogenates from intestinal smooth muscles does not justify any definitive conclusions about the character of its effect on the smooth-muscle activity. PMID- 6269350 TI - Effect of cholecystokinin octapeptide sulphate ester on brain monoamines in the rat. AB - The effect of different doses of intracerebro-ventricularly administered cholecystokinin octapeptide sulphate ester (CCK-8-SE) was studied on dopamine (DA), norepinephrine (NE) and serotonin (5-HT) contents in the hypothalamus, mesencephalon, amygdala, septum and striatum, 10, 20 and 60 min following administration. The DA and NE content increased and the 5-HT content decreased in the hypothalamus and mesencephalon. A biphasic action was observed in the amygdala of DA, NE and 5-HT depending upon the time and doses used. Similar action was seen on DA and NE in the septum. In the striatum, the DA and 5-HT content decreased while the NE level first increased and then decreased. The data indicate that the CCK-8-SE is able to modify the activity of DA, NE and 5-HT in different brain regions in a time and dose-dependent manner, with a local specific action. PMID- 6269352 TI - Influence of newly-synthetized xanthine derivatives on phosphodiesterase with high Km in homogenates of different organs and on lipolysis in vivo. AB - Six newly-synthetized 7-N-basically substituted xanthine derivatives were studied for inhibitory action on phosphodiesterase with high Km in homogenates from brain, lung and epididymal fatty tissue. Theophylline is used for comparative purposes. The effect of part of the compounds on lipolysis in vivo is also studied. Some of the newly-synthetized compounds are found to manifest a marked ability to inhibit the enzyme studied in brain and lung homogenates, and compound with code V has equal action to that of theophylline. The newly-synthetized compounds are poor inhibitors of the enzyme in epididymal fatty tissue, unlike theophylline which demonstrates the same inhibitory capacity as in the other homogenates. These data correlate with the results obtained when studying lipolysis. Theophylline in a dose of 50 mg/kg i. p. increases twice the serum content of the free fatty acids, while the newly-synthetized compounds have no effect on it, even when applied in high doses. PMID- 6269353 TI - Formation of ectopic neuromuscular junctions in adult rats. AB - The formation of ectopic neuromuscular junctions between a transplanted foreign nerve (the superficial fibular nerve) and the denervated soleus muscle was examined in adult rats. Formation of new junctions was induced by denervating the soleus muscle by cutting the tibial nerve. Junctional transmission began 3 days after denervation when denervation was done 3 weeks after transplantation of the foreign nerve, and progressively later when denervation was done 8, 16 and 24 weeks after transplantation. The rate at which the transmission, once started, acquired mature characteristics was approximately the same in each case. Initially, spontaneous m.e.p.p.s were infrequent, long lasting with a skewed amplitude distribution. The e.p.p.s evoked by stimulation of the foreign nerve were then commonly below threshold for eliciting action potentials and were occasionally no larger than the size of the spontaneous m.e.p.p.s. M.e.p.p. characteristics became normal in the 2nd week after transmission had started. Fully effective evoked transmission with every innervated fibre responding with overshooting action potential occurred 1-3 months after onset of transmission. PMID- 6269354 TI - Beta-adrenergic control of peripheral vascular resistance during increased sympatho-adrenal activity. PMID- 6269355 TI - Role of GABA-ergic receptors for the synthesis of GABA in different compartments of the rat cerebellum. PMID- 6269356 TI - Circadian patterns of growth hormone, prolactin and corticotrophin secretion in hypothalamic and extra-hypothalamic lesions localized by stereotactic neuro radiology in humans. AB - The integrity of mediobasal hypothalamus for the maintenance of normal circadian rhythms has been clearly established in the animal. Using precise stereotactic neuroradiologic localisations of various brain tumors, the authors demonstrate that in human, cortical lesions induce no significant modifications of the circadian variation of GH, prolactin or ACTH. In contrast subcortical lesions displacing the 3rd ventricle result in an inhibiton of the nocturnal rise in GH and prolactin, whereas the circadian rhythm of ACTH remains normal. PMID- 6269357 TI - [Research of correlations between psychological, somatic, and endocrine data in 56 cases of female anorexia nervosa (author's transl)]. PMID- 6269358 TI - Distribution of the extrahepatic uptake in liver diseases as recorded by scintigraphy. AB - Liver scintigraphy performed with 99Tcm-S and Sn colloid ought to be named RES scintigraphy as the distribution of the colloid is mainly determined by the phagocytic capacity of the RES but also by the regional blood flow and the features of the colloid. Both diffuse hepatocellular disease and malignant disease may have decreased activity in the liver and increased extrahepatic activity: spleen, bone marrow and lungs. In liver cirrhosis at least 3 types of distribution of activity can be recognized: (a) equal increase in spleen, bone marrow and lungs, (b) mainly increase in spleen, and (c) mainly increase in bone marrow and lungs. Therefore a ratio between the total extrahepatic and the hepatic activity ought to be calculated rather than a spleen/liver ratio. PMID- 6269359 TI - Cholangiographic findings in ulcerative colitis. AB - Endoscopic retrograde cholangiography (ERC) was performed in 28 patients with hepatobiliary disease associated with ulcerative colitis. The films were reviewed and correlated with diagnoses at liver biopsy. Thirteen patients with extrahepatic as well as intrahepatic bile duct abnormalities had characteristic cholangiographic findings compatible with sclerosing cholangitis, together with cholangiocarcinoma in one patient. Six patients had intrahepatic bile duct involvement only, and the cholangiographic abnormalities differed from those of sclerosing cholangitis. In 5 of these patients cirrhosis of the liver was found at biopsy or clinically. The result indicates that in patients with hepatobiliary disease suggested in association with ulcerative colitis, ERC gives valuable information. PMID- 6269360 TI - Sputum cytology of a metastatic postradiation sarcoma (malignant fibrous histiocytoma). AB - A female patient who died of apparent postradiation sarcoma in the inguinal region after irradiating a metastatic squamous cell carcinoma of the same site was reported. For approximately 20 months, the patient had received a total of 6,600 and 9,600 Roentgen to the right para-aortic and inguinal areas, respectively. About 10 years later, she developed a sarcoma, namely a malignant fibrous histiocytoma. Sputum cytology demonstrated numerous giant cells with bizarre nuclei; subsequent chest films also presented apparent metastatic tumor shadows. The cellular characteristics and also rather low incidence of detection of nonepithelial malignant tumor by sputum cytology were briefly discussed, and ways of enhancing cytodiagnostic accuracy were proposed. PMID- 6269361 TI - Complete in vitro replication of SV40 DNA and chromatin in saponin-treated permeable cells. AB - A permeable cell system has been developed by treatment with saponin for studying in vitro replication of DNA and chromatin. DNA replication of simian virus 40 nucleoprotein complexes (SV40 chromatin) in saponin-treated permeable cells was found to be more efficient than that in digitonin-treated permeable cells. Autoradiography of the agarose-gel revealed that [alpha-32P]dCTP was incorporated into SV40 DNA I, II and replicating intermediates. The time course of the incorporation indicated complete replication of SV40 DNA and chromatin with a full number of nucleosomes. The saponin-treated permeable cell system will serve as a useful system for studying in vitro replication of DNA and chromatin in eukaryotic cells. PMID- 6269363 TI - Mapping of evoked responses from different areas of hypothalamus on stimulation of spermatic nerve in monkeys. AB - Stainless steel pedestal was implanted on the skull of 12 adult anesthetized rhesus monkeys, according to the predetermined stereotaxic coordinates of hypothalamus. For recording, conscious monkey was made to sit on its chair in a shielded cage to minimize interfering artifacts. Spermatic nerves were stimulated with concentric needle electrodes inserted into undissected portion of the spermatic cord and evoked responses were recorded from a number of hypothalamic areas. Responses with initial negative and positive phases appeared in the anteromedial and posterior hypothalamic regions respectively. The middle medial portions of hypothalamus showed non-conductive local activity, while the lateral regions at the same anteroposterior co-ordinates gave responses, which showed a positive negative response more on a pattern of primary sensory motor cortex. The results indicate smaller latency zones in medial part and longer latency in anterior and posterior parts, and suggest that hypothalamic excitation occurs via periventricular fiber system. PMID- 6269362 TI - Serodiagnosis of type A hepatitis by detection of immunoglobulin M-type antibody to hepatitis A virus. AB - Serum specimens from 12 patients with type A hepatitis were analyzed for immunoglobulin M-type antibody to hepatitis A virus (IgM anti-HA). A recently developed solid-phase radioimmunoassay kit for IgM anti-HA (HAVAB-M, Abbott Laboratories) and a competitive binding radioimmunoassay kit (HAVAB, Abbott Laboratories) with or without 2-mercaptoethanol treatment, as modified by Yano et al. (Acta Hepatol. Jpn. 21, 704-712, 1980) were used to obtain an M-index. All specimens obtained within 60 days of the onset of illness and specimens from 2 of 4 patients later than 60 days after the onset were positive with the HAVAB-M test. This test gave negative results to sera which were positive for anti-HA by a standard HAVAB test in the following: 3 patients with type B hepatitis; 5 with non-A, non-B hepatitis; 11 healthy adults; and 10 sera strongly positive for rheumatoid factor. The M-index for type A hepatitis in sera within 30 days of the onset (mean value of the M-index, m, = 1.52; standard deviation, SD, = 0.25) was significantly higher than that for non-A hepatitis (m = 1.05; SD = 0.15) and for healthy adults (m = 1.02; SD = 0.10). The simplicity and usefulness of the HAVAB M test in diagnosis of acute type A hepatitis over those measuring the M-index by HAVAB tests were shown by direct comparison of the results. PMID- 6269364 TI - The effects of brainstem transection on respiratory activity in the rabbit. AB - Mid-sagittal incisions and transverse hemisections of the medulla were performed in rabbits anaesthetized with halothane and artificially ventilated at eupnoeic level. A midsagittal incision extending from the obex to (at least) 4 mm rostral elicited asynchronous (independent) firing in both phrenic nerves. A subsequent transverse hemisection interrupted the activity of the ipsilateral phrenic nerve. An electrical stimulation of the vagal input temporarily restored this activity. A midsagittal incision, which had not completely separate both halves of the medulla, did not affect the synchrony of firing of both phrenic nerves; in these cases also the transverse hemisection did not arrest the phrenic nerve activity. It is concluded that synchronous activity of the inspiratory output depends upon intact connnections crossing in the lower medulla and that proper generation of respiratory pattern depends upon a critical level of excitation created by neurones at rostral pontine and suprapontine levels of the CNS, neighboring structures (presumably including the medial reticular formation) and/or vagal input. A concept of a "critical mass" of active neurones is introduced. PMID- 6269365 TI - Respiratory activity generated by a split brainstem preparation of the rabbit. AB - Mid-sagittal incisions of the brainstem were performed in anaesthetized, vagotomised, paralysed and artificially ventilated rabbits. The activity of both phrenic nerves, blood pressure and end-tidal CO2 percent were continuously monitored. The results fell into two groups: in one of them a relatively small separation of both halves of the medulla extending from the obex to at least 4 mm rostrally elicited asynchronous firing in both phrenic nerves ("split respiratory centre"). In the other group, in which the incisions were placed either more caudally or more rostrally, or when small strands of the nervous tissue were left to provide connections between both sides of the brainstem, this. phenomenon did not appear. It is concluded that there are two symmetrical respiratory networks in both halves of. the brainstem and that their synchronous firing depends upon intact connections extending from the obex to the caudal end of nucleus of VII nerve. PMID- 6269366 TI - Cerebellar interaction with the acoustic reflex. AB - The involvement of the cerebellar vermis in the acoustic reflex was analyzed in 12 cats, decerebrated or in pentobarbital anesthesia. Anatomical data suggested the existence of a connection of lobules VIII with the ventral cochlear nucleus. Single cell recording and evoked potential techniques demonstrated the existence of the acoustic projection to lobulus VIII. Electrical stimulation of this area changed the tension of the middle ear muscle and caused evoked potential responses in the caudal part of the ventral cochlear nucleus. Electrical stimulation of the motor nucleus of the facial nerve evoked a slow wave in the recording taken from the surrounding of the cochlear round window. A hypothesis is proposed which postulates the involvement of the acoustic reflex in space localization of acoustic stimuli and the action of cerebellar vermis in order to assure the stability and plasticity of the acoustic reflex arc. PMID- 6269367 TI - Cerebral space-occupying cysts following radiation and chemotherapy of malignant gliomas. AB - Eight cases of cerebral cyst formation among 50 patients (= 16%) with malignant supratentorial gliomas treated by surgery, megavoltage radiation, and multiple agent chemotherapy are reported. Five of them developed signs of intracranial hypertension or progressive neurological deficit, while in three patients cerebral cysts were detected by CT without clinical deterioration. At operation or autopsy, or both, the large fluid-filled, smooth-walled cysts were lined by glio-mesenchymal scar tissue with no or little tumour recurrence in five, while three patients showed large recurrent tumour masses associated with necrosis and cyst formation. Clinical signs or CT evidence, or both, of cerebral cysts developed 4 to 12 months (average 10 months) after the first craniotomy, and 3 to 9 months after termination of radiotherapy, usually after the second to fourth course of polychemotherapy. The cystic cavities which are attributed to increased necrosis and other effects of radiation and cytostatic treatment, may mimic tumour progression or recurrence, and cerebral abscess, but are usually recognized by CT. Surgical treatment produced transient clinical improvement in 5 patients, but usually did not prevent the fatal outcome of the disease, which in these paticrosis and other effects of radiation and cytostatic treatment, may mimic tumour progression or recurrence, and cerebral abscess, but are usually recognized by CT. Surgical treatment produced transient clinical improvement in 5 patients, but usually did not prevent the fatal outcome of the disease, which in these paticrosis and other effects of radiation and cytostatic treatment, may mimic tumour progression or recurrence, and cerebral abscess, but are usually recognized by CT. Surgical treatment produced transient clinical improvement in 5 patients, but usually did not prevent the fatal outcome of the disease, which in these patients occurred 3 weeks to 6 months after surgical treatment of cyst formation, their life span ranging from 9 to 22 months. The pathogenesis and clinical problems related to cerebral cysts arising following multimodality treatment of malignant brain tumours are discussed. PMID- 6269368 TI - Stereotactic biopsy of intracranial space occupying lesions. AB - The results of stereotactic biopsies of intracranial expanding lesions with narrow instruments both prior to and during the CT era are evaluated in 345 patients. Eighty-four cystic lesions were needled and roughly classified. Small, cystic, or solid tumours in anatomically well-defined areas such as the sellar, the third ventricle, and the pineal regions were as easily punctured and classified without as with CT scanning. When larger tumours in different compartments were punctured the biopsy verification rate increased from 55% towards 91% if an enhanced CT investigation was included. A stereotactic biopsy is a fairly safe procedure, yielding in this series a mortality less than 1% and a morbidity of 2.3%. PMID- 6269369 TI - Anaerobic change of bloody CSF in subarachnoid haemorrhage. Its relation to cerebral vasospasm. AB - In our in vitro study of subarachnoid haemorrhage, the anaerobic incubation of CSF-blood mixture led to marked fall in the pH value thereof, which suggested to us that intracranial focal acidosis may play some role in the pathogenesis of cerebral vasospasm or disturbance of consciousness after the haemorrhage. To test this hypothesis, we treated 16 clinical cases of such disorders with carotid injection of 7% sodium bicarbonate solution. The treatment resulted in considerable improvement of the disturbance of consciousness by dilating the cerebral peripheral arteries; this we could observe angiographically 15 minutes after carotid injection. We found no morphological changes, however, in the spastic vessel itself up to 30 minutes after the injection. Given the result both of this study and of our previous experiments, we offer the hypothesis that the synthesizing process of thromboxane A2 and intracranial focal acidosis might play an important role in the pathogenesis of cerebral vasospasm. PMID- 6269370 TI - The transformation of cell growth and transmogrification of DNA synthesis by simian virus 40. PMID- 6269371 TI - Structural diversity among retroviral gene products: a molecular approach to the study of biological function through structural variability. PMID- 6269372 TI - Immune deficiency predisposing to Epstein-Barr virus-induced lymphoproliferative diseases: the X-linked lymphoproliferative syndrome as a model. PMID- 6269373 TI - Mobile receptor and collision coupling mechanisms for the activation of adenylate cyclase by glucagon. PMID- 6269374 TI - Theoretical simulation of a model describing hormone receptor--adenylate cyclase coupling. AB - We have shown that current knowledge of the coupling between receptor and cyclase, as expressed in terms of the proposed model, can account for the nonlinear coupling between cyclase activation by hormone and receptor-occupancy, and for the effects of GTP on hormone-binding. Such demonstrations require mathematical analysis and numerical simulation. The results can be used as theoretical support for intuitive interpretations of observed behavior and can predict consequences of variations in the concentration of the elements of the system (R, G, E). PMID- 6269375 TI - Isolation and characterization of the beta-adrenergic receptor of frog erythrocytes and development of potential affinity ligands. PMID- 6269376 TI - Autoantibodies and monoclonal antibodies to beta-adrenergic receptors: their use in receptor purification and characterization. PMID- 6269377 TI - Molecular pharmacology of adenylate cyclase-coupled alpha- and beta-adrenergic receptors. PMID- 6269378 TI - Receptor-mediated stimulation and inhibition of adenylate cyclases: the fat cell as a model system. PMID- 6269379 TI - Adenosine receptors and the regulation of adenylate cyclase. PMID- 6269380 TI - Escherichia coli adenylate cyclase as a sensor of sugar transport function. AB - Adenylate cyclase of E. coli is a membrane-bound enzyme the function of which is to synthesize a cofactor for processes that are important in metabolic transitions. The depletion from the environment of a supply of a preferred carbon source dictates the requirement for initiating the synthesis of a new metabolic system; this synthesis will require cAMP. After the adaptation period, the requirement for a high level of synthesis diminishes, resulting in a diminished requirement for cAMP. A mechanism for regulating the activity of adenylate cyclase accomplishes the variation in the required cellular cAMP concentrations. In the absence of a transportable carbon source, adenylate cyclase activity is activated by cellular regulators; when carbon sources are transported, the cellular activators are dissipated, resulting in inhibition of adenylate cyclase activity. This scheme is summarized in Fig. 6. Sugar transport systems fall into two categories: one in which the energy for the process comes from PEP (the PTS) and one in which the energy comes from the proton electrochemical gradient. Adenylate cyclase communicates with both of these systems by interacting with intermediates on the pathway to energy generation for driving these two transport processes. Adenylate cyclase couples indirectly to a large array of sugar specific transport systems by interacting with intermediates common to all the processes. The net result of this regulatory mechanism is that, without physically communicating with the extracellular environment by spanning the membrane, adenylate cyclase effectively senses the presence of external sugars that interact with cells that have become competent to transport them. PMID- 6269381 TI - Purification and properties of the regulatory component (G/F) of adenylate cyclase. PMID- 6269382 TI - Genetic analysis of cyclic nucleotide phosphodiesterases in Drosophila melanogaster. PMID- 6269383 TI - Phosphatidylinositol hydrolysis and calcium signaling. AB - The salivary glands of the blowfly possess two separate 5-HT receptors. One receptor system is linked to adenylate cyclase to produce cyclic AMP, which regulates cation transport across the epithelium. The other receptor acts through calcium, which stimulates anion transport. Activation of this second receptor is associated with the specific hydrolysis of phosphatidylinositol (PI) to give a PI response that appears to be a characteristic feature of receptors that act through calcium. Studies on this insect gland have established a close correlation between PI hydrolysis and changes in calcium gating. The idea that these two receptor-mediated events might be intimately related was strengthened by the observation that the ability of 5-HT to gate calcium could be varied by adjusting the level of PI in the membrane. PMID- 6269384 TI - The structure of adenylate cyclase systems. PMID- 6269385 TI - Cyclic GMP-dependent protein kinase in intestinal brushborders. PMID- 6269386 TI - Cyclic AMP derivatives as tools for mapping cyclic AMP binding sites of cyclic AMP-dependent protein kinases I and II. PMID- 6269387 TI - The role of calmodulin, troponin, and cyclic AMP in the regulation of glycogen metabolism in mammalian skeletal muscle. PMID- 6269388 TI - Reconstitution of the primary action of a hormone receptor using solubilized components. PMID- 6269389 TI - Calcium and cyclic AMP-dependent regulation of myofibrillar calmodulin-dependent myosin light chain kinases from cardiac and skeletal muscles. PMID- 6269390 TI - Functional compartmentation of cyclic AMP and protein kinase in heart. PMID- 6269391 TI - Growth regulation of S49 lymphoma cells: analysis of cAMP responsiveness and polyamine metabolism. PMID- 6269392 TI - Calmodulin and cyclic AMP-dependent protein kinases mediate calcium-induced stimulation of DNA synthesis by rat liver cells. PMID- 6269393 TI - Involvement of cAMP in the cytoplasmic control of meiotic cell division in Xenopus laevis oocytes. AB - 1) There is a large body of evidence for an inhibitory role for cAMP in progesterone induced meiosis in amphibian oocytes consistent with its known inhibitory activity in mammalian oocytes (5,26). It implies that the action of steroid hormones in this particular tissue is mediated by modifications of cAMP levels within the cell. 2) Bacterial toxins have proved to be useful reagents in the investigation of the regulatory role of cyclic nucleotides in the resumption of cell division in amphibian oocytes. 3) The possible involvement of cGMP in these processes needs to be further investigated. PMID- 6269394 TI - Pseudohypoparathyroidism: an inherited disorder of adenylate cyclase. PMID- 6269395 TI - Phosphorylating proteins as effectors in malignant cell transformation. PMID- 6269396 TI - In vitro transformation with Rous sarcoma virus and the pp60src-associated protein kinase. AB - Fifteen transformation defective sensitive mutants of Rous sarcoma virus have been investigated to see if the expression of the pp60src-associated protein kinase activity correlated with other parameters of transformation such as altered growth control, morphological changes, increased hexose transport, and increased plasminogen activator protease synthesis. The expression of a protein kinase activity paralleled or preceded the onset of other parameters of transformation with but one exception: altered control of cell growth. The stability of the pp60src molecule in mutant-infected cells at the nonpermissive temperature was investigated with the finding that mutant pp60src did not show an increased turnover at the nonpermissive temperature as compared to wild type virus pp60src. Furthermore, it could be shown that pre-existing pp60src in mutant infected cells maintained at the non-permissive temperature became activated after temperature shift to the permissive temperature. Temperature shift performed under conditions of inhibition of new protein synthesis with cycloheximide, puromycin, or emetine was followed by greatly increased protein kinase activity, and a parallel phosphorylation of pp60src itself in tyrosine residues. Morphological features of transformation could be demonstrated likewise under conditions of inhibition of protein synthesis. PMID- 6269397 TI - Thyroid control: an example of a complex cell regulation network. PMID- 6269398 TI - Hormonal regulation of amino acid transport in isolated rat hepatocytes: properties of a high affinity transport component induced by glucagon and cyclic AMP. AB - In isolated rat hepatocytes, glucagon and cyclic AMP induce in vitro the emergence of a high affinity component of amino acid transport similar to that induced by fasting or partial hepatectomy, situations characterized by high plasma glucagon levels (10,11). This high affinity component has the properties of a pure A system, is operative for both AIB entry and AIB exodus, is dependent on de novo protein synthesis and has a rapid rate of degradation. The high affinity of this transport system, as well as its strong specificity for amino acids sharing the A mediation, represent a mechanism whereby the liver can adjust to increased needs for amino acids for gluconeogenesis, or for macromolecular synthesis. It appears from our studies that glucagon can rapidly stimulate amino acid transport through the synthesis of high affinity carriers which, in addition, are characterized by a rapid rate of degradation. This rapid turnover may be essential for enabling the hepatocyte to adjust its amino acid transport activity to varying environmental conditions. PMID- 6269399 TI - Interdependent effects of thyroid hormones and cAMP on lipolysis and lipogenesis in the fat cell. PMID- 6269400 TI - Mediators of the effects of ACTH on adrenal cells. PMID- 6269401 TI - ACTH-stimulated changes in the immunocytochemical localization of cyclic nucleotides, protein kinases, and calmodulin. PMID- 6269402 TI - Hormonal control of Leydig cell function. PMID- 6269403 TI - Opioid-dependent dual regulation of adenylate cyclase in a cell-free system. PMID- 6269404 TI - Regulation by neurohormones of cyclic AMP concentration in cells derived from the nervous system. PMID- 6269405 TI - Cyclic AMP modulation of a specific ion channel in an identified nerve cell: possible role for protein phosphorylation. AB - Multidisciplinary studies of the role of cAMP in synaptic transmission have been made possible by the favorable properties of the molluscan nervous system, and there is now evidence from several laboratories implicating cAMP in physiological responses in various Aplysia nerve and muscle cells (9,10,15,18,21). The results we have obtained satisfy all the criteria (8) necessary to establish that cAMP mediates the response to a neurotransmitter: a) the response is mimicked by intra or extracellular application of cAMP derivatives, and by activation of adenylate cyclase within R15; b) a phosphodiesterase inhibitor enhances the response to low concentrations of serotonin; c) serotonin causes cAMP to accumulate within R15, and stimulates adenylate cyclase activity in membranes prepared from R15 cell bodies; and d) the serotonin receptors mediating adenylate cyclase stimulation and R15 hyperpolarization are pharmacologically very similar. This is the first time all these criteria have been satisfied in a neuronal system, and thus we conclude that the serotonin-induced increase in potassium conductance in neuron R15 is mediated by cAMP. PMID- 6269406 TI - Regulation of the beta-adrenergic receptor by methylation of membrane phospholipids. AB - Stimulation of the beta-adrenergic receptor increases the enzymatic methylation of membrane phospholipids. Increased synthesis of phosphatidyl-N monomethylethanolamine by methyltransferase I increases fluidity and enhances the ability of the beta-adrenergic receptor to couple with adenylate cyclase. The number of beta-adrenergic receptors can be regulated by the rate of synthesis and of degradation of phosphatidylcholine formed by transmethylation. PMID- 6269408 TI - Physicochemical properties of field and cell culture-attenuated strains of swine transmissible gastroenteritis (TGE) coronavirus. PMID- 6269407 TI - Agonist-specific desensitization: molecular locus and possible mechanism. PMID- 6269409 TI - Studies on the egg-drop syndrome. PMID- 6269410 TI - A live attenuated virus vaccine against sheep pox. PMID- 6269411 TI - Studies on porcine adrenocortical function. I. Circadian variations in, and effect of ACTH treatment on, the peripheral plasma cortisol level. PMID- 6269412 TI - Primary oat cell carcinoma of the larynx. AB - Oat cell carcinoma of the larynx is a rare and highly malignant tumor. Five cases are reported and the world literature is reviewed. Three of the five patients had distant metastases when they were first seen with hoarseness. The radiographic and histologic findings and treatment regimen for one patient are described, as well as correct recommendations for therapy of these tumors. PMID- 6269413 TI - Influence of heart rate and atrial transport on left ventricular volume and function: relation to hemodynamic changes produced by supraventricular arrhythmia. AB - The response of the left ventricle to pacing-induced changes in heart rate and the atrioventricular (A-V) relation was examined with equilibrium gated radionuclide ventriculography in 20 patients who had normal ventricular function after surgery for recurrent supraventricular tachycardia. In 10 patients count derived left ventricular ejection fraction, end-diastolic volume and stroke volume were measured during sinus rhythm and during atrial pacing at 120, 140 and 160 beats/min. In the other 10 patients similar determinations were made during sequential A-V and simultaneous ventricular and atrial (V/A) pacing, both at rates of 100 and 160 beats/min. Left ventricular ejection fraction did not change significantly with atrial pacing (from 0.65 +/- 0.02 [mean +/- standard error of the mean] at a baseline sinus rate of 91 +/- 3 beats/min to 0.62 +/- 0.03 at 160 beats/min) despite a progressive decrease in end-diastolic volume. The percent reduction in end-diastolic volume (% delta EDV) and stroke volume (+ delta SV) from the baseline values was linear and related to change in heart rate (delta HR) as % delta EDV = -0.60 delta HR + 5.19 (r = 0.71; p less than 0.01) and % delta SV = -0.62 delta HR + 5.03 (r = 0.76; p less than 0.001). Left ventricular ejection fraction with baseline sequential A-V pacing at 100 beats/min was 0.67 +/- 0.03 and not significantly altered by either sequential A-V or simultaneous V/A pacing at 160 beats/min. At 100 beats/min, loss of atrial transport with simultaneous V/A pacing resulted in a small reduction in end-diastolic volume from a baseline value of -9.0 +/- 1.9 percent (p less than 0.01) and a nonsignificant reduction in stroke volume of -3.7 +/- 1.6 percent. During simultaneous V/A pacing at 160 beats/min, the reduction in end-diastolic and stroke volumes from the baseline value was -26.6 +/- 3.8 percent and -28.8 +/- 4.3 percent, respectively (both p less than 0.01), but was significantly smaller (-16.1 +/- 3.6 percent and -19.2 +/- 4.1 percent, respectively [p less than 0.05]) when atrial transport was maintained during sequential A-V pacing at the same heart rate. During simultaneous V/A pacing at 160 beats/min, two thirds of the reduction in end-diastolic and stroke volumes from the baseline value was due to the increment in heart rate as assessed from sequential A-V pacing and the other third was due to loss of atrial transport. The data indicate that the hemodynamic consequences of supraventricular tachyarrhythmias in patients with normal ventricular function are due primarily to decreases in ventricular volume as heart rate is increased and atrial contribution is lost rather than to any changes in left ventricular ejection fraction. PMID- 6269414 TI - Dynamic coronary tone in precipitation, exacerbation and relief of angina pectoris. AB - Until recently, understanding of the pathogenesis of angina pectoris was based primarily on the concept of a fixed stenosis of one or more coronary arteries: Myocardial ischemia and angina occurred when myocardial oxygen consumption (MVO2) outstripped the capacity of the diseased coronary artery to delivery oxygen. Therapeutic strategies focused on interventions designed to reduce MVO2. The concept of dynamic obstruction, first applied to coronary spasm induced at rest and more recently to spasm induced by exercise, adds an additional important pathophysiologic mechanism responsible for causing angina pectoris. This study deals with the possibility that the concept of "spasm," as commonly understood, is too narrowly defined. It develops the hypothesis that subcritical increases in large vessel coronary tone occur, either in a "normal" coronary artery or in one with an existing lesion, that augment the degree of large vessel coronary resistance but not enough to exceed the vasodilator reserve of the coronary arterioles. Hence, although total coronary resistance, and thereby coronary flow, is unaltered at rest, the impingement on arteriolar vasodilator reserve would diminish the capacity to augment flow in response to increases in MVO2. Such coronary constriction would not precipitate angina at rest but would increase anginal threshold. Conversely, dilatation of a stenotic coronary artery could decrease the degree of obstruction and increase anginal threshold. This concept of dynamic coronary obstruction in the presence of "normal" or diseased coronary arteries implies a direct role for coronary vasodilators in some patients with angina pectoris, even when frank coronary spasm is absent. Also implicit in this hypothesis is the concept that dynamic and fixed components to obstruction may contribute variably to the degree of obstruction in different patients. Some patients with largely fixed obstruction would benefit mainly from attempts to lower MVO2 with nitrates and beta blocking agents. Dynamic coronary obstruction may constitute the major mechanism responsible for angina in other patients. In these persons nitrates or calcium channel blocking agents might provide the most efficacious form of therapy. Both fixed and dynamic obstruction may play an important role in symptom production in yet other patients. In such persons attempts to decrease MVO2 and the magnitude of coronary obstruction might provide the most successful form of therapy. PMID- 6269415 TI - Functional organization of the oculomotor nucleus in the baboon. AB - The functional organization of the oculomotor nucleus was investigated using horseradish peroxidase (HRP) histochemistry. In a series of baboons, injections of HRP were made into the skeletal muscles supplied by the oculomotor nerve (medial rectus, superior rectus, inferior rectus, inferior oblique, and the levator palpebrae superioris). After a 48-hour survival time the animals were sacrificed via perfusion-fixation and the brains treated according to the tetramethylbenzidine (TMB)-HRP method of Mesulam (1978). The inferior oblique, inferior rectus, medial rectus, and levator palpebrae superioris muscle are supplied by cells located primarily in the homolateral oculomotor nucleus. Some fibers to the levator palpebrae superioris arise from cells in both caudal central nuclei. The superior rectus muscle receives fibers from cells in the contralateral oculomotor nucleus. The results were compiled using a Lucite-plate reconstruction method that permits visualization of the three-dimensional configuration of the neuronal populations within the oculomotor nucleus. Oculomotor neurons are organized in a vertical column that may be anatomically divided into rostral, middle, and caudal thirds. A section through any of these levels may be further subdivided into dorsal, intermediate, and ventral zones. Each of the oculomotor skeletal muscles was found to have cells at almost all levels of the nucleus and in certain zones at each level. These functional cell groups intermingle with one another in the baboon and do not remain segregated into distinct subnuclei or subdivisions. Much overlap was evident between cells innervating the homolateral inferior rectus, homolateral inferior oblique, and the contralateral superior rectus muscles. There was also overlap between those cells supplying the homolateral levator palpebrae superioris and the homolateral medial rectus muscles. PMID- 6269416 TI - Acute effects of increased meat protein on urinary electrolytes and cyclic adenosine monophosphate and serum parathyroid hormone. AB - The effect of a high meat protein diet on urinary electrolytes, cyclic AMP, and serum immunoassayable parathyroid hormone was studied in six subjects fed a high meat protein diet (1.5 to 2.9 g/kg) for 7 days. The diet produced minor decreases in serum calcium and phosphorus but increased endogenous creatinine clearance by about 20% (p less than 0.02) and urinary calcium by about 80% (p less than 0.01) without changing urinary sodium. Urinary calcium correlated (p less than 0.01) with urinary sulfate (r = 0.60), ammonia (r = 0.72), and nitrogen (r = 0.60). Urinary cyclic AMP increased (p less than 0.01) 14% while serum parathyroid hormone (measured by C-terminal assays) decreased (p less than 0.05) by more than 30%. It was concluded 1) that this diet acutely altered renal handling of calcium at a site different from that of sodium, 2) that the excretion of acidic products of protein metabolism contributed to these changes, and 3) that parathyroid hormone secretion was not changed acutely. PMID- 6269417 TI - Long-term feeding of unavailable carbohydrate gelling agents. Influence of dietary concentration and microbiological degradation on adaptive responses in the rat. AB - Guaran, tragacanth, gum arabic, carrageenan, gum karaya, and methylcellulose were used in a long-term feeding study to evaluate their effects upon adaptive responses of nutritionally controlled parameters in rats by feeding a fiber-free diet containing increasing additions of polysaccharides. In general, supplements reduced weight increases due to lower energy intakes. Only in the case of microbiologically inert polysaccharides the dilution of the the energy density was partially compensated by an increased food intake. Neither of the polysaccharides fed, however, decreased energy utilization. All polysaccharides similarily increased small intestinal length up to about 30% without grossly altering mucosal protein and DNA per unit of length. Concerning their effects on the colon and the cecum, polysaccharides behaved differentially according to their accessibility to microbiological degradation. Inert polysaccharides exerted a more pronounced effect on the colon whereas the others mainly increased cecum weight. Degree and locus of the observed changes are determined mainly by the dietary concentration of the polysaccharides and their accessibility to bacterial degradation within the intestinal tract. PMID- 6269418 TI - Effect of fiber from fruits and vegetables on metabolic responses of human subjects: fiber intakes, fecal excretions, and apparent digestibilities. AB - Intakes and excretions of fiber were determined for 12 men consuming controlled diets containing fruits and vegetables (high fiber diet) or fruit and vegetable juices (low fiber diet) for periods of 26 days. The fiber in the low fiber diet appeared to be mostly hemicellulose, with an apparent digestibility of 95%. Apparent digestibilities of hemicellulose, cellulose, and lignin in the high fiber diet were 88, 42, and 18%, respectively. Small amounts of uronic acids were detected in the feces, but there is no certainty that they were derived from pectin. Linear regressions indicate that fiber intakes, rather than fiber disappearance, influenced the fecal volume. PMID- 6269419 TI - Aspiration biopsy cytology of the salivary gland. AB - Aspiration biopsy by fine needle from the major salivary glands has been an under utilized technic in the United States. To evaluate this form of biopsy, 69 patients with salivary gland enlargement were examined by this technic; 47 had confirmative histology. Characteristic ABC patterns were seen in the benign mixed tumor, the papillary cystadenoma lymphomatosum, the mucoepidermoid carcinoma, and malignancy metastatic to the salivary gland. These findings are described. The method proved complication-free and accurate and is recommended for all tumors of the salivary gland. PMID- 6269421 TI - Evaluation of methods for detection and quantitation of fetal cells and their effect on RhIgG usage. AB - A 1980 College of American Pathologists Immunohematology Survey included two erythrocyte suspensions, one with and one without fetal cells, designed to evaluate methods for detecting and quantitating fetomaternal hemorrhage in Rh immune globulin candidates. Data from a supplementary questionnaire regarding Rh immune globulin administration during 1979 were compared by methods used. The most commonly used screening test was the microscopic Du. With this test, 12.2% of nearly 2,000 laboratories obtained a false negative result on an unknown which contained approximately 0.6% Rh positive erythrocytes. On this 100% adult cell suspension two-thirds of laboratories using acid elution technics reported the presence of fetal cells. Laboratories using Fetaldex to screen for and quantitate fetomaternal hemorrhage had the highest rate of false positives on this unknown and reported higher rates of multiple vial Rh immune globulin administration when compared to institutions using other acid elution procedures. The second unknown in this survey contained approximately 0.4% fetal cells. About one third of laboratories, using each of four acid elution technics, reported values less than one half to more than twice this amount. The number of false positive and false negative results and the wide scatter of quantitation amounts reported for these two unknowns suggest that better methods are needed for screening and quantitating fetomaternal hemorrhage. PMID- 6269420 TI - Comparison of complement fixation and fluorescent immunoassay (FIAX) for measuring antibodies to cytomegalovirus and herpes simplex virus. AB - An automated fluorescent immunoassay system (FIAX) was compared with complement fixation (CF) for measuring antibodies to cytomegalovirus (CMV) and herpes simplex virus (HSV) in clinical specimens. Compared with CF the specificity of FIAX (ability to detect a negative titer) was 95% for CMV and 92% for HSV. The sensitivity of FIAX (ability to detect a positive titer) was 98% for CMV and 95% for HSV. When paired samples were tested for significant titer rises, the concordance of the two assays for CMV was 96% and for HSV 80%. The FIAX assay was found to be reproducible when sera were tested within the same laboratory and in two different laboratories. The assay is fast, simple to perform, and not affected by anticomplementary activity. It is seen as a useful alternative to CF testing in a clinical virology laboratory. PMID- 6269423 TI - Delta-9-tetrahydrocannabinol as an antiemetic. AB - The use of delta-9-tetrahydrocannabinol (THC) as an antiemetic in patients undergoing cancer chemotherapy is reviewed. The pharmacokinetics of THC is discussed, and the agent's effects on the central nervous, cardiovascular, respiratory, gastrointestinal, immune, endocrine, and reproductive systems are presented. The toxicology, potential hazards, and adverse reactions of THC are reviewed. Also reviewed are studies of THC's use as an antiemetic. THC appears to be an effective antiemetic in cancer patients undergoing chemotherapy. The maximal antinauseant effects often correlate with the attainment of a "high". THC has been found consistently more effective than placebo and at least as effective as prochlorperazine. In phenothiazine-resistant patients, THC's effectiveness has exceeded that of the phenothiazines. Efficacy may depend on the chemotherapeutic agent causing emesis. Elderly patients do not tolerate the THC "high" well. Concurrent administration of phenothiazines with THC may block the "high" without reducing THC's antiemetic effectiveness. Because of variations in individual tolerance, absorption, and the form of chemotherapy, flexibility is necessary in establishing the correct dose of THC. PMID- 6269422 TI - Familial hypogammaglobulinemia with variable serum immunoglobulins. Concordance with lymphocyte ecto-5'-nucleotidase deficiency. AB - Four male subjects from two generations of a black family were found to have variable expression of hypogammaglobulinemia (IgG, IgM, and IgA deficiency in two, IgA deficiency in one, and IgM and IgA deficiency in another) and also to be moderately deficient in the lymphocyte plasma membrane enzyme, 5'-nucleotidase. The inheritance pattern of the immune abnormality is compatible with X linkage. The affected patients had normal numbers of complement receptor-bearing lymphocytes, variably depressed proportions of IgM- and IgD-bearing lymphocytes, and impaired ability to synthesize antibody after specific antigenic stimulation. In this family, the 5'-nucleotidase deficiency and the pattern of inheritance suggest that the different types of hypogammaglobulinemia may represent a variable expression of a common underlying genetic abnormality. PMID- 6269424 TI - In vitro effect of penicillins and aminoglycosides on commonly used tests for glycosuria. AB - The effect of penicillins (ampicillin, carbenicillin, penicillin G, and penicilloic acid) and aminoglycosides (amikacin, gentamicin, streptomycin, and tobramycin) on the accuracy of Clinitest, Diastix, and TesTape determinations of glycosuria was studied. Solutions of each of the drugs were prepared in urine in a range of clinically obtainable drug concentrations. In addition, urine solutions were prepared that contained the same drug concentrations and sufficient glucose to give final concentrations of 0.5, 1, and 2%. All solutions were tested in triplicate using the five-drop Clinitest method, Diastix, and TesTape. Falsely elevated and falsely decreased Clinitest readings were obtained with the penicillins. These readings were influenced by the concentration of the penicillins and of glucose. The aminoglycosides had no effect of Clinitest determinations. Neither drug class interfered with Diastix or TesTape readings. The Clinitest-penicillin interaction is unpredictable. If Clinitest is used as a quantitative test for glycosuria in patients receiving penicillins, the results should be rechecked using a qualitative method such as the glucose oxidase tests, Diastix or TesTape. All three tests can be used to test for glycosuria in patients receiving aminoglycosides. PMID- 6269425 TI - Fever in renal transplant recipients: causes, prognostic significance and changing patterns at the University of Minnesota Hospital. AB - During a three year period in which 433 renal transplants were performed, 194 episodes of fever were documented in allograft recipients hospitalized at the University of Minnesota. Viral infections were responsible for over half of the febrile episodes, and 98 (51 percent) of the fevers were associated with cytomegalovirus (CMV), either occurring alone or in conjunction with allograft rejection or another systemic infection. Bacterial infections, fungal infections and rejection were other important causes of fever, accounting for 14 percent, 5 percent and 13 percent of the febrile episodes, respectively. Most fevers occurred in the first four months after transplantation; although about two thirds of these fevers were due to CMV, only 17 percent of fevers that occurred more than one year after the renal transplant were due to CMV. Bacterial and fungal infections and malignancy were important causes of these fevers. Of the febrile illnesses associated with transplant nephrectomy or death, a majority occurred in patients with CMV disease. Secondary bacterial and/or fungal infections were observed in a large majority of patients with lethal CMV disease. During the third year of this study there was a significant decrease in the proportion of febrile episodes due to CMV. PMID- 6269426 TI - Use of cefotaxime, a beta-lactamase stable cephalosporin, in the therapy of serious infections, including those due to multiresistant organisms. AB - Cefotaxime is a cephalosporin active against most gram-positive and gram-negative organisms, including streptococci, Staphylococcus aureus, Enterobacteriaceae, Proteus, and many Pseudomonas and Bacteroides fragilis--all but the latter two are inhibited at concentrations below 0.5 micrograms/ml. We evaluated cefotaxime as the sole therapy for 32 infections in 31 patients. Infection sites included 18 bacteremias; pulmonary, urinary tract, deep tissue infections; and meningitis. Clinical cures were achieved in 88 percent and bacteriologic cures in 86 percent of the patients--including those with infections due to organisms resistant to cephalosporins, chloramphenicol, carbenicillin and aminoglycosides; and in two patients with meningitis due to multiresistant Klebsiella pneumoniae. Serum and cerebrospinal levels were readily maintained above the inhibitory levels of susceptible organisms. Adverse reactions were minimal. Cefotaxime was a safe, effective antibiotic in the treatment of infections due to susceptible organisms, including those resistant to other agents. PMID- 6269427 TI - Neurologic manifestations of systemic vasculitis. A retrospective and prospective study of the clinicopathologic features and responses to therapy in 25 patients. AB - A combined retrospective and prospective study of a patient population with either or both biopsy and angiographic evidence of systemic necrotizing vasculitis was undertaken in order to delineate the neurologic manifestations of this syndrome. The type, extent and natural history of the lesions in the peripheral and central nervous system were evaluated, together with the response fo the nervous system disease to corticosteroids or cytotoxic agents or both. In 60 percent of the patients, there was involvement of the peripheral nervous system. Four patterns of neuropathy were seen: mononeuritis multiplex, extensive mononeuritis, cutaneous neuropathy and polyneuropathy. The central nervous system was involved in 40 percent of the patients, manifested predominantly by diffuse and focal disturbances of cerebral, cerebellar and brain stem function. This study demonstrates the complexity and heterogeneity of the neurologic complications of the systemic necrotizing vasculitides. With treatment of the vasculitic process and prevention of further insult, both the peripheral and central nervous system make significant, and at times, dramatic, recovery. PMID- 6269428 TI - Idiopathic familial chondrocalcinosis due to apatite crystal deposition. AB - Idiopathic familial chondrocalcinosis was found in five members of a family. The clinical features of the disease were morning stiffness, pain and limitation of motion of the dorsolumbar spine in four of the five members, associated with arthritis of the small joints of the hands in three, shoulder periarthritis in two and costal cartilage pain in one. Radiologically, four of the five patients had multiple intervertebral disk calcifications, mainly located at the nucleus pulposus area. Three of them also had periarticular calcific deposits, associated with costal cartilage calcifications and degenerative changes in the small joints of the hands in two. None of these cases showed cartilage calcification in the knees, public symphysis or triangular ligament of carpus. In the propositus, optical microscopy of a specimen of the second proximal interphalangeal joint obtained by open biopsy showed the presence of multiple calcified areas in the intercellular matrix and chondroid metaplasia with calcification of the matrix in the synovial membrane and capsule. X-ray diffraction studies, energy dispersive analysis, and infrared spectrophotometry of a costal cartilage sample obtained by open biopsy demonstrated the presence of carbonate calcium hydroxyapatite. In this study, no relation was found between HLA antigens, loci A, B and C, and this syndrome due to calcium hydroxyapatite crystal deposition. PMID- 6269429 TI - Past and current roles for cephalosporin antibiotics in treatment of meningitis. Emphasis on use in gram-negative bacillary meningitis. AB - The therapy of gram-negative bacillary meningitis is less than adequate to date; the agents recommended do not achieve bactericidal levels in purulent cerebrospinal fluid. Because optimal antibiotic therapy of meningitis occurs when the cerebrospinal fluid level of an antibiotic is above the concentration needed to kill the offending pathogen, another group of agents needs to be considered. The newer cephalosporins or cehalosporin-type antibiotics (cefotaxime, moxalactam), by virtue of their marked activity against gram-negative bacilli and their ability to achieve significant CSF levels, merit serious consideration as therapy for gram-negative bacillary meningitis. Investigators in Europe and the United States have developed preliminary data demonstrating the efficacy of these agents in a growing number of cases. In the group presented herein, of the 35 cases in which gram-negative bacillary meningitis was treated with the newer cephalosporins, there were only four failures. PMID- 6269430 TI - Sex differences in lung and adrenal neurosympathetic development in rabbits. AB - To assess the possible mechanism for the increased incidence and severity of the respiratory distress syndrome (RDS) in male versus female infants, we studied neurosympathetic development in the lung and adrenal glands in male and female fetal and newborn rabbits. Tissue levels of catecholamines, norepinephrine (NE), epinephrine (E), and dopamine (DA) were measured using a sensitive radioenzymatic assay. Beta adrenergic receptor development in the lung was studied using the tritiated radioligand dihydroalprenolol. Neurosympathetic innervation of the lung was assessed by measuring tissue NE levels, which increased gradually from 27-day fetuses to 8-day-old newborns. Sex differences were not significant. Lung beta receptor number was significantly elevated in females as compared with males at each gestational age and throughout the neonatal period (p less than 0.005). Adrenal gland content of E, NE, and DA increased exponentially with advancing developmental age (each p less than 0.005). Adrenal E was significantly (p less than 0.01 elevated in female as compared with male fetuses, as was the proportion of E. Adrenal NE and DA were similar in male and female fetuses. Sex differences were not significant in the newborn animals. The significant relative delay in adrenal medullary and lung beta-receptor matration may relate to the male susceptibility to neonatal morbidity and neonatal RDS. PMID- 6269431 TI - Dissociation of chorioadenoma destruens from hydatidiform mole by urinary steroid analysis. AB - Dissociation between hydatidiform mole (HM) and chorioadenoma destruens (CA) was attempted by gas chromatographic analysis of urinary steroids. In the chromatogram, fraction 2 (F2) including four pregnane steroids (17 hydroxypregnanolone, pregnanolone, pregnanediol, and pregnanetriol) reflected the biologic activity of molar human chorionic gonadotropin (hCG), and the ratio of F2 to fraction 1 (F1) (17-ketosteroids) was found useful in monitoring secondary growth of trophoblastic tumor: Urinary log F2/F1 after curettage declined quickly and unidirectionally in HM, but the same parameter exhibited a temporal rise in CA at 11 to 20 days after curettage because of the molar hCG from residual tumor tissue. The resolution between HM and CA at that stage (11 to 20 curettage days) was of the order of diagnostic use and superior to that with immunoreacive hCG. The data obtained are discussed in the light of pathophysiology of CA. PMID- 6269432 TI - Role of neutrophils in dilation during parturition. PMID- 6269433 TI - Separate turnover of cytochrome c and myoglobin in the red types of skeletal muscle. AB - The purpose of this investigation was to determine whether cytochrome c and myoglobin have similar turnover rates in the three types of skeletal muscles. Exercise (endurance training) was used as an inducing stimulus to increase their concentrations. The half-lives (t 1/2) were subsequently estimated from the time course of return to base-line levels after cessation of exercise. When exercise was stopped, cytochrome c concentration returned rapidly to control levels; the lengths of t 1/2 were approximately 8 days in fast-twitch red, 5 days in slow twitch red, and 9 days in mixed muscles. These findings confirm previous results of cytochrome c turnover. The concentration of myoglobin decreased at a slower rate than that observed for cytochrome c during detraining in fast-red slow-red, and plantaris muscles, and did not return to sedentary control levels throughout the 50-day detraining period. Myoglobin concentration in fast-twitch white muscle did not increase with the training. These results provide evidence that the degradation rate of myoglobin differs from that of cytochrome c in the red types of skeletal muscle. These elevated myoglobin levels may, in part, provide one explanation for the slow rate of decline in aerobic power that has been observed when individuals stop exercising. PMID- 6269434 TI - Transport properties of toad kidney epithelia in culture. AB - The characteristics of a continuous line of toad kidney epithelial cells (A6) are described. These cells form a monolayer epithelium of high transepithelial electrical resistance (about 5,000 omega . cm2). The cells generate a transepithelial potential difference (apical surface negative) of about 9 mV. The short-circuit current is equivalent to net sodium flux. Net sodium flux is stimulated by aldosterone and by analogues of cAMP. The stimulation is readily reversible. Neither urea permeability nor osmotic water flow is altered by analogues of cAMP. Amiloride eliminates 90% of the short-circuit current. Thus A6 cells form an epithelium with several differentiated properties including hormonal regulation of transport. PMID- 6269435 TI - FSH and testosterone effects in seminiferous tubules of immature hypophysectomized rats. AB - The effects of follicle-stimulating hormone (FSH) and testosterone on the development of the cytosolic germ cell adenylate cyclase and germ cell morphology in rats hypophysectomized at 29 days of age were studied. Following hypophysectomy, the adenylate cyclase content fell to marginal levels and germ cell development ceased at the late pachytene stage. Testosterone treatment led to a moderate increase in the cytosolic enzyme content and to progression of spermatid cell development to stages 8-12. FSH treatment with doses of 80-100 micrograms/day restored enzyme content to levels seen in control rats, as well as progression of germ cell development up to stages 15-16, i.e., to the same stages present in age-matched control (sham-operated) rats. The results indicate that in immature rats FSH is essential for spermatid cell maturation as is evidenced by its ability to stimulate the formation of cytosolic germ cell adenylate cyclase to quantitatively normal levels, as well as to stimulate the development of spermatid cells. PMID- 6269436 TI - Functional segmentation of the mammalian nephron. AB - Although each of the major experimental techniques applied to the study of renal physiology has provided its fair share of new information, the technique of in vitro microperfusion of nephron segments is notable for two major contributions. First, it has supplied a more direct and controlled means of studying epithelial transport processes, some of which already have helped us to understand certain aspects of kidney function and others of which have yet to find their application in unraveling the mysteries of the kidney. Second, in the process of delineating these transport characteristics, it has served to emphasize the epithelial specialization present in the kidney, providing functional counterparts to the already recognized anatomic heterogeneity present in the kidney. In this second role microperfusion has spawned the application of biochemical analysis of the hormonal responses of various nephron segments and contributed to the impetus for work in culturing the various cell types present in each nephron segment. This review outlines the functional characteristics of the 11 major segments of the nephron, incorporating what has been learned from some of the biochemical work on hormone response and correlating the latter with transport events. PMID- 6269437 TI - Spectrophotometric monitoring of O2 delivery to the exposed rat kidney. AB - Optical spectrophotometry was used to measure changes in the oxidation-reduction state of cytochrome c oxidase in the in situ rat kidney. Alterations in the redox state of cytochrome c oxidase were monitored during variations in the amount of oxygen being delivered to the animal. Spectral analyses were performed on whole kidney, cortical tubule suspensions, and blood (the latter flowing freely through surgically implanted femoral arteriovenous shunts). Reaction spectra identified the location of the absorption maxima for reduced cytochrome c oxidase to be at approx. 605 nm. Additional spectral analysis indicated that hemoglobin oxygenation-deoxygenation changes had minimal artifactual interference on the cytochrome redox signals. The present results indicate that mitochondrial cytochrome c oxidase is not maximally oxidized in the in situ kidney of anesthetized rats at arterial oxygen in the in situ kidney of anesthetized rats at arterial oxygen tensions within the normal physiological range. The redox state of the enzyme in vivo is altered by changes in the level of inspired oxygen over a wide range. The current data are consistent with the existence of nonuniform regions of aerobic respiration occurring in the in situ kidney. PMID- 6269438 TI - Short-term effect of aldosterone on Na-K-ATPase in single nephron segments. AB - One of the theories proposed to explain the action of mineralocorticoids on target tissues attributes their effect on cation transport to stimulation of the "sodium pump." To test this hypothesis we evaluated the short-term effect of aldosterone on Na-K-ATPase in discrete nephron segments microdissected from kidneys of adrenalectomized animals. Na-K-ATPase activity measured in proximal and distal nephron segments from adrenalectomized as well as intact mice remained unchanged 1 or 3 h after a single injection of D-aldosterone (10 micrograms/100 g body wt i.p.). Similarly, no effect of aldosterone could be demonstrated in experiments in vitro, in which tubules from adrenalectomized mice and rabbits were incubated (90 min, 37 degrees C) in the presence of physiologic or pharmacologic concentrations of the hormone (3.10(-10) to 3.10(-6) M). These studies did not show an effect of aldosterone on isolated tubule Na-K-ATPase within the time interval in which this hormone alters tubular cation transport and therefore do not support the "pump theory" of mineralocorticoid action. PMID- 6269439 TI - Antisecretory effects of berberine in rat ileum. AB - The in vitro antisecretory effects of the alkaloid berberine (1.0 mM) on intestinal ion secretion and mucosal adenylate cyclase and Na-K-ATPase activities were studied in the rat ileum. Mucosal berberine did not alter the individual basal net ion fluxes and basal adenylate cyclase activity but decreased short circuit current (Isc) and increased the net absorption of chloride plus bicarbonate. In the cholera toxin-treated tissue, mucosal berberine stimulated absorption of Na and Cl and inhibited the increased adenylate cyclase activity but did not change the specific Na-K-ATPase activity, whereas serosal berberine stimulated Na secretion and decreased Isc. Mucosal berberine also decreased Isc, increased Cl permeability, and reversed the ion secretion induced by dibutyryl cyclic AMP, the heat-stable enterotoxin of Escherichia coli, and methylprednisolone administration. The antisecretory effects of mucosal berberine may be explained by stimulation of a Na-Cl-coupled absorptive transport process. The mechanism of action of serosal berberine remains to be elucidated. However, it is clear that mucosal berberine affects intestinal ion transport by mechanisms different from stimulation of the Na pump and probably at a step distal to the production or degradation of cyclic AMP or cyclic GMP. PMID- 6269440 TI - Brain receptor binding and central actions of angiotensin analogs in rats. AB - The possible physiological importance of brain receptors for angiotensin was investigated. Structure-activity relationships were established for 12 fragments and analogs of angiotensin II (ANG II). 1) Affinities of the peptides were determined in an in vitro assay of rat brain angiotensin receptors. 2) Blood pressure (BP) and water intake following intracerebroventricular administration of the peptides to conscious rats were monitored. In vitro, ANG II and [des Asp1]ANG II displayed the highest affinities. [Trp1]ANG II and [Trp8]ANG II had one-eighth and one-ninth the affinity of ANG II, respectively. Multiple substitutions in positions 1, 4, and 8 produced a 1,000-fold fall in binding affinity. Excellent correlation was found between the in vitro binding affinities and the in vivo central activities of the peptides on BP (r = 0.975) and on water intake (r = 0.900). The results suggest that the biochemically characterized brain angiotensin receptors may be physiologically relevant to BP and body fluid homeostasis. The brain angiotensin receptors mediating BP and thirst have very similar structural requirements. PMID- 6269441 TI - Role of sympathetic system in morphine-induced mydriasis in rat. AB - The effects of three doses (5, 30, and 60 mg/kg) of morphine on pupillary diameter (PD) were studied in rats that were either normal, neurotransmitter antagonist pretreated, guanethidine pretreated, cervical sympathectomized, or adrenalectomized. Morphine produced a dose-dependent increase in PD and exophthalmos. In addition, the PD concurrently underwent fluctuations. alpha Adrenergic antagonists blocked both mydriasis and exophthalmos, whereas a beta adrenergic antagonist had no significant effect. This suggested a role for the sympathetic nervous system. However, cervical sympathectomy or guanethidine pretreatment only partially blocked the increase in PD or exophthalmos. Adrenalectomy also partially blocked the mydriasis and exophthalmos. Adrenalectomy combined with guanethidine pretreatment completely blocked morphine induced mydriasis but no exophthalmos. Thus, the results suggest that both direct sympathetic innervation and hormonal action from the adrenals are involved in morphine-induced mydriasis in the rat. PMID- 6269442 TI - Pituitary beta-endorphin, naloxone, and feeding in several experimental obesities. AB - The role of beta-endorphin in the development of several obesity syndromes was examined. Adult female hooded rats received ventromedial hypothalamic lesions, dorsolateral tegmental lesions, parasagittal hypothalamic knife cuts, intraventricular 5,7-dihydroxytryptamine, ovariectomy, control surgery, or were deprived to 75% of normal body weight. Dose-dependent suppression of food intake by the opiate antagonist naloxone (0.5, 1.8, 6.8, or 25.0 mg/kg, ip) was measured during once-daily 4-h food access periods. No difference was found among the groups at any dose. Pituitary beta-endorphinlike immunoreactivity (BELI) was substantially decreased in knife-cut rats, but was unaltered by other treatments. Obesity had no effect on BELI. In another experiment, rats made obese by prolonged maintenance on palatable foods had elevated pituitary BELI levels. Feeding mechanisms involving opioid peptides do not appear to be of etiological significance in the syndromes examined. PMID- 6269443 TI - Effects of adrenergic blockade on glucose kinetics in septic and burned guinea pigs. AB - We have used the primed-constant infusion of [6-3H]glucose to study the effects of phentolamine, an alpha-adrenergic blocker, and propranolol, a beta-adrenergic blocker, on glucose production and clearance in gastrostomy-fed control, septic (repeated sub-Q Escherichia coli injections), and burned (25-30% BSA) guinea pigs. Hypermetabolism and elevated glucoregulatory hormones were evident in both traumatized models, whereas their glucose kinetic response was different. Basal glucose production and clearance were elevated in the burned group and were depressed in the septic group when compared to control values. Propranolol caused a further increase in glucose production and clearance in the burned group, whereas it depressed glucose production and clearance to an even greater extent in the septic group. Phentolamine also produced an increase in glucose production and clearance in the burned group. In the septic group, phentolamine had no significant effect on glucose production, but clearance was significantly elevated. Thus, although alpha- or beta-adrenergic blockade normalized metabolic rate in both groups with respect to control animals, glucose kinetics remained different despite similar changes in counterregulatory hormones. PMID- 6269444 TI - Stress reactions involving the pars interarticularis in young athletes. AB - A stress reaction involving the pars interarticularis of the lumbar spine was confirmed in seven young athletes with a positive technetium pyrophosphate bone scan. No pars defects were detectable on their lumbosacral roentgenograms, which included oblique views. The return to normal levels of radioactive uptake on repeat bone scans correlated closely with their clinical course. If the bony reaction is recognized early, it may heal at a subroentgenographic level and prevent the development of lumbar spondylolysis. These early lesions usually show unilateral increased uptake at one lumbar level on the bone scan and, initially, the athlete localizes the pain to the corresponding unilateral lumbar paraspinous area. The "one-legged hyperextension test" is positive on the ipsilateral side and aggravates the pain. Treatment consists of avoiding the aggravating activities and resting. The average time for return to pain-free competition was 7.3 months. These developing defects may be the source of considerable prolonged disability in the young athlete, particularly if undiagnosed and untreated. PMID- 6269445 TI - The myxoid tumors of somatic soft tissues. AB - Tumors and tumorous conditions of superficial and deep soft tissues may owe their naked-eye appearance and much of their bulk to the accumulation of mucopolysaccharide material or, on rare occasions, to edema. The so-called myxoid tumors may be chondroblastic, fibroblastic, lipoblastic, myoblastic, or neurogenic. Benign and malignant tumors may be encountered. Naked-eye and microscopic appearances are described. Pseudotumors such as bursae, ganglia, cutaneous mucinoses, fasciitis, and myxoid cysts may enter the differential diagnosis. The value of accurate documentation is stressed. Histochemistry can make a limited contribution to diagnosis. The entities described have been examined with regard to alcian blue staining with and without pretreatment with hyaluronidase. Alcian blue staining in the presence of increasing concentrations of magnesium chloride has been investigated and found to be of value in the identification of tumors of chondroblastic origin. PMID- 6269446 TI - Lectin and toxin-like activities of Entamoeba histolytica: comparison of properties. AB - A comparison was made between properties of a recently discovered Entamoeba histolytica lectin which has a carbohydrate specificity for N-acetylglucosamine oligosaccharides and the previously found toxin-like principle of the ameba. A separation between these two activities was achieved upon subcellular fractionation by high speed centrifugation of freeze-thawed disrupted E. histolytica trophozoites (strain HM-1). Practically all of this lectin activity, as determined by hemagglutination of glutaraldehyde-fixed human erythrocytes, was found associated with the sedimented membrane fraction. This fraction did not affect monolayers of tissue-cultured mammalian cells. On the other hand, the soluble supernatant solution caused extensive damage to the tissue-cultured cells (change in morphology and detachment of cells). Both the lectin and toxin activities were heat-labile and their activities were preserved by the presence of reducing agents and proteolytic enzyme inhibitors. In contrast to the toxin, the isolated lectin was inactive at pH 7.2 and active only at pH 5.7-6.0. Both the lectin and toxin were inhibited by a number of macromolecular compounds such as chitin, peptidoglycan, bovine serum and an IgA fraction isolated from human colostrum. Only the lectin activity, however, was inhibited by low molecular weight chitin oligosaccharides (GlcNAc)n=2-6 or by lysozyme-digested peptidoglycan subunits. Moreover, fetuin and a ganglioside mixture extracted from ox brain were found to inhibit only the toxin-like activity. The IgG fraction of sera from patients with invasive amebiasis neutralized both lectin and toxin-like activities, while IgG from normal sera failed to neutralize either activity. Although our results indicate that in E. histolytica, lectin and toxin are two separate activities, both of them share a considerable number of properties which does not exclude the possibility that they may be related. PMID- 6269447 TI - Total pancreatectomy for ductal adenocarcinoma of the pancreas. Mayo Clinic experience. AB - This review reveals that, once again, surgical therapy of ductal adenocarcinoma of the pancreas has been thwarted, probably by the inherent biologic aggressiveness of this particular malignancy. The operative mortality rate (greater than 10 percent) coupled with the 5 year survival rate of 2.3 percent is eloquent testimony to this. Multicentric disease occurred in one third of the patients, whereas extrapancreatic spread was found in half of the resected specimens. At 1 year, the only statistically favorable determinants were multicentricity and female sex. The main bonus of total pancreatectomy appears to be the elimination of pancreatojejunal anastomosis with its lethal complications. PMID- 6269448 TI - Artificial pancreas as an aid during insulinoma resection. AB - Blood glucose control by an artificial pancreas facilitated the intraoperative management of two patients with insulin-secreting pancreatic islet cell tumors (one had a large adenoma, the other diffuse islet-cell hyperplasia). The artificial pancreas is a glucose-controlled insulin and dextrose infusion system uniquely suited for the control of blood glucose concentrations during surgery. The artificial pancreas produced a stable glycemic baseline before surgery, prevented hypoglycemia during palpation of the pancreas and manipulation of the tumor, and indirectly amplified small decreases in the blood sugar level with large increases in the rate of dextrose infusion. The advantages and limitations of continuous glucose monitoring during surgery and the use of this instrument in locating occult insulin-secreting tumors are reviewed. PMID- 6269449 TI - [Hormonal receptors and their importance in obstetrics and gynecology]. PMID- 6269450 TI - Treatment of life-threatening arrhythmias. PMID- 6269452 TI - Intracranial hemorrhage following administration of sodium bicarbonate in rabbits. AB - Studies on the correlation between hyperosmolality and brain damage, especially intracranial hemorrhage, were carried out on young and newborn rabbits following infusion with 7% sodium bicarbonate. 1) All the young rabbits injected with 7% sodium bicarbonate died of hyperosmolality at over 380 mOsm/L (the mean was 462 mOsm/L) after drip infusion at the rate of 20-60 ml/kg/hr. Young rabbits under a 10% hypoxic environment died even at the 350 mOsm/L level (the mean was 392 mOsm/L) during infusion of 7% sodium bicarbonate. Half of the case of newborn rabbits injected with 7% sodium bicarbonate at 10 ml/kg, intraperitoneally, had intracranial hemorrhage at 335 mOsm/L. When the hyperosmolality reached 392 mOsm/L (50 ml/kg), intracranial hemorrhage was observed in all cases. 2) The main cause of death in young and newborn rabbits was subdural hemorrhage in the subtentorial region. Intraventricular hemorrhage was observed in about 40% of the cases of young and newborn rabbits. 3) The blood pH was elevated by the drip infusion, but when the hyperosmolality reached about 400 mOsm/L, the blood pH began to fall. At the same osmolality, pCO2 showed a marked elevation. It is likely that the decrease of the blood pH was caused by the elevation of pCO2 and the outflow of H+ from intracellular compartments resulting from the hyperosmolality. These results apparently indicate that fatal intracranial hemorrhage was induced by hyperosmolality and was enhanced by the combination of hypoxia and immaturity. PMID- 6269451 TI - Medical pathology conference: hypoglycemia and recurrent upper gastrointestinal bleeding in a 58-year-old white man. PMID- 6269453 TI - Surgical treatment of tumors in the newborn. AB - With the exception of hemangiomas, neoplasms occur in newborn infants once per 15,000 births. These tumors are mostly derived from embryonic mesenchymal or neural crest tissues and consists of teratomas, neuroblastomas, and tumors of the kidneys and soft tissues. Many of these neoplasms are very malignant in older children, while the same tumor type in the newborn is generally well circumscribed and has a benign biological behavior. Therefore, the surgical treatment should be conservative. The operative is conducted with attention to the minute details that support the metabolic needs of the infant. The management of specific tumors encountered in the neonate are described. PMID- 6269454 TI - Radiation therapy in the neonate. AB - Radiation therapy (RT) is frequently used in the management of children with cancer, but neonatal neoplasms are rare. Newborns represent 1.5% of the children with malignant diseases in the Tumor Registry at the Children's Hospital of Philadelphia over the last 30 years. Thus, occasionally the pediatrics radiation therapist must consider treating the very young infant. The specific radiation effects on growth and development must be weighed in reaching a therapeutic decision. All children are vulnerable to the late effects of radiation therapy, but the neonates may be more susceptible because of the immaturity of important organs such as the brain, lung, liver, kidney, and bone. In general, radiation therapy, should be avoided during the first several weeks of life because of the potential increased sensitivity of the liver and kidneys during that period. If radiation therapy is used at all during infancy, the benefits must be weighed against the possibility of significant late effects. Increasing knowledge of pediatric neoplasms has shown that some tumors (such as mesoblastic nephroma) require no treatment except for surgical excision; and other tumors, such as Stage IV-S neuroblastoma, may require very little treatment. In those tumors that require radiation therapy, the use of chemotherapy may allow reduction of the radiation dose. Furthermore, alterations of time-dose-fractionation schemes and careful attention to tumor volume with the use of special techniques, such as "shrinking fields," may decrease the late adverse effects of treatment. PMID- 6269455 TI - Cerebrospinal fluid GABA and cyclic nucleotides in alcoholics with and without seizures. AB - Cerebrospinal fluid levels of gamma-aminobutyric acid (GABA) and cyclic nucleotides were measured in alcoholic and control patients. Alcoholics without seizures had higher GABA levels than either alcoholics with seizures or controls. Levels of cyclic AMP and cyclic GMP in cerebrospinal fluid of controls and alcoholics with and without seizures were not significantly different. PMID- 6269456 TI - Rapid large-scale purification of pig heart nucleoside diphosphate kinase by affinity chromatography on Cibacron Blue 3G-A Sepharose. PMID- 6269457 TI - A new method for separating cyclic AMP from 5'-AMP with application to the assay for cyclic AMP phosphodiesterase. PMID- 6269458 TI - Purification, stabilization, and characterization of rat hepatic triglyceride lipase. PMID- 6269459 TI - Simultaneous extraction and assay of cyclic nucleotides, prostaglandins, and DNA from cat alveolar bone. PMID- 6269460 TI - An assay specific for the active form of liver phosphorylase kinase. PMID- 6269461 TI - A continuous spectrophotometric assay for Clostridium histolyticum collagenase. PMID- 6269462 TI - Fractionation of simian virus 40 DNA fragments by RPC-5 column chromatography. PMID- 6269463 TI - Purification of some tricarboxylic acid cycle enzymes from beef heart using affinity elution chromatography. PMID- 6269464 TI - A rapid boiling method for the preparation of bacterial plasmids. PMID- 6269465 TI - Interaction of tritiated beta-endorphin with rat brain membranes. PMID- 6269466 TI - Quantitative studies of ion-exchange and affinity elution chromatography of enzymes. PMID- 6269467 TI - Laboratory evaluation of selected disinfectants as virucidal agents against porcine parvovirus, pseudorabies virus, and transmissible gastroenteritis virus. AB - Of a variety of disinfectants evaluated, only sodium hypochlorite and sodium hydroxide inactivated porcine parvovirus (PPV) after a 5-minute incubation period. After the same incubation time, pseudorabies and transmissible gastroenteritis viruses were inactivated by all of the disinfectants tested. When the incubation time was increased to 20 minutes, 2% glutaraldehyde and a double strength concentration of a commercial formaldehyde preparation also inactivated PPV. Formaldehyde vapor and ultraviolet radiations inactivated PPV also, but relatively long exposure times were required. PMID- 6269468 TI - In utero transmission of bovine leukemia virus. AB - In an initial study, 18 calves born to cows persistently infected with bovine leukemia virus (BLV) were tested for infective virus and antibodies at birth, and no infected or seropositive animals were found. Four of these calves were maintained in quarters where infected animals were housed, and 3 of the 4 subsequently became infected. These were probably contact infections acquired during, or at some time after, birth. The remaining 14 calves were kept in isolation pens in a building housing no infected cattle. None of this group was found to be BLV infected during 1 year of observation. In further studies, 15 pregnant cows inoculated with BLV became infected. One abortion, considered to be unrelated to the BLV inoculation, occurred 38 days later. The remaining 14 cows gave birth to 1 dead and 14 live calves. The dead calf and its live twin were seropositive for BLV at birth, indicating that they had been infected in utero. The remaining 13 calves were negative for BLV antibodies at birth and remained so during 1 year of observation. PMID- 6269469 TI - Bluetongue in cattle: a serologic survey of slaughter cattle in the United States. AB - Serologic tests for bluetongue virus (BTV) were done on 19,758 blood serum samples systematically collected at brucellosis laboratories throughout the United States from Nov 28, 1977 to Feb 20, 1978. Prevalence of BTV antibody varied from 0 to 79% of the samples collected in various states, with a national prevalence of 18.2%. The prevalence was generally low in the northern states and high in the southwestern states. The highest prevalence rates were found in Puerto Rico and the Virgin Islands. PMID- 6269470 TI - Antibody response of calves after intranasal inoculation with parainfluenza-3 virus and resistance of inoculated calves to experimental homologous viral infection. AB - The immunologic response of colostrum-deprived calves to parainfluenza-3 (PI-3) virus given by intranasal inoculation was studied. Inoculation of calves with 3.2 x 10(6) median cell culture infective doses (CCID50) of either virulent (SF-4) virus or a modified strain of PI-3 virus, or with 2.0 x 10(8) CCID50 of SF-4 virus, stimulated development of both serum antibody and nasal secretion (NS) antibody. However, NA antibody decreased in all calves between the 16th and 42nd postinoculation days and was present only at low or moderately low concentrations on the 126th day, when the immunity of the calves was challenged. Generally, calves that were inoculated with 3.2 x 10(6) CCID50 of SF-4 virus developed slightly higher concentrations of serum and NS antibodies than did calves inoculated with modified virus. Calves that were inoculated with 2.0 x 10(8) or 3.2 x 10(6) CCID 50 of SF-4 virus developed comparable concentrations of serum antibody, but large doses of SF-4 virus were less effective than smaller doses of the same virus in stimulating the development of NS antibody. Reinoculation of 3 calves with modified PI-3 virus resulted in a demonstrable increase in serum antibody in 2 calves and an increase and subsequent decrease in NS antibody in all calves. Challenge exposure of inoculated calves to aerosols of SF-4 virus failed to cause clinical signs of disease, and the challenge virus was not isolated from the nasal passages. PMID- 6269471 TI - The causes of cancer. PMID- 6269472 TI - Angiotensin converting enzyme concentrations in rabbits with talc-induced pulmonary granulomas. AB - Pulmonary foreign body granulomas were induced in rabbits by intravenous injection of a talc suspension, and serum angiotensin converting enzyme (ACE) concentrations were monitored for 50 days. One of 3 treated rabbits responded with a slight elevation of serum ACE in the third week after the first injection and for the remainder of the experimental period. Two treated rabbits and 2 control rabbits maintained serum ACE concentrations close to the starting values throughout the observation period of 50 days. We concluded that pulmonary talc granulomas and probably other foreign body granulomas do not elicit a major elevation of serum ACE in rabbits. PMID- 6269473 TI - Insidious cutaneous lesions of the head and neck. PMID- 6269474 TI - [Thanatophoric dwarfism. Apropos of 2 cases, one of them with cytomegalic inclusion disease and hepatic hamartoma]. PMID- 6269475 TI - Progressive disseminated histoplasmosis; favorable response to ketoconazole. AB - Four patients with disseminated histoplasmosis, two of whom had late relapses after previous therapy with amphotericin B, were treated with ketoconazole 200 to 400 mg daily for 1 year. All patients improved markedly during therapy, with resolution of symptoms decreasing liver and spleen size, and weight gain; resolution of oral ulcers occurred in the two patients in whom they were present. Decrease in serum alkaline phosphatase levels correlated well with clinical improvement. One patient who was much improved while receiving ketoconazole continued to harbor Histoplasma capsulatum in an abdominal aortic aneurysm, which became symptomatic 4 months after cessation of the drug. He underwent aneurysmectomy, and H. capsulatum isolated from the resected aneurysm was susceptible in vitro to ketoconazole. No significant adverse reactions to the drug were noted despite prolonged therapy. Our results indicate that ketoconazole may have a role in the therapy of disseminated histoplasmosis in adults. PMID- 6269476 TI - [Double-blind comparative trial of trimethoprim-polymyxin B and trimethoprim sulphacetamide-polymyxin B ear drops in the treatment of otorrhoea (author's transl)]. AB - The purpose of his double-blind, randomized trial was to compare ear drops containing either trimethoprim and polymyxin B (TP) or trimethoprim, sulphacetamide and polymyxin B (TSP) from the points of view of effectiveness and safety. The 68 patients treated had otitis externa or recurrent otitis media with perforated ear-drum, or mastoid cavity with post-tympanoplasty infection. Satisfactory results were obtained in 60.6% of the cases with TP and in 88.6% with TSP. When evaluated by the Chi-square method with Yates' correction, the difference was statistically significant. There was no evidence of ototoxicity, fungal infection or local hypersensitivity with either preparation. The trial demonstrated that both ear drops were active and that TSP was much more effective than TP in the treatment of otorrhea. PMID- 6269477 TI - Sinusoidal harmonic acceleration test in clinical practice. AB - The author's experience during the first year of use of the Sinusoidal Harmonic Acceleration test in clinical practice is presented. The advantages of this test both in the diagnostic and monitoring areas are illustrated with patient evaluation summaries. Further, use of this test on a daily basis in the office practice of neurotology will define its role in the evolution and follow-up of neurotologic problems. PMID- 6269478 TI - Concentration of serum thyroid hormone binding proteins after 131I treatment of hyperthyroidism. AB - Serum concentrations of the thyroid hormone binding proteins, thyroxine binding globulin, prealbumin, and albumin were determined in 30 thyrotoxic patients before and after 131I treatment. Each patient was placed into one of three groups according to response to treatment. The serum concentration of all three proteins rose significantly in 10 patients who became euthyroid, and a greater increase was seen in 10 patients who developed hypothyroidism. There was no significant change in thyroid hormone binding protein concentrations in 10 subjects who remained hyperthyroid. Changes in the concentration of thyroid hormone binding proteins should be borne in mind when total thyroid hormone concentrations are used to monitor the progress of patients receiving treatment for hyperthyroidism. PMID- 6269479 TI - Acute non-bacterial infections of the respiratory tract in Singapore children: an analysis of three years' laboratory findings. AB - A retrospective study of the laboratory results on respiratory specimens received from children under 12 years of age between January 1977 and December 1979 was carried out. These children were either hospital patients, usually with lower respiratory infections, or outpatients on the Influenza Surveillance Programme. The overall virus isolation rate was 26.8%, and the isolation rate among hospital patients, 38.5%. Epidemics or outbreaks were associated with infections due to the influenza viruses, respiratory syncytial virus (RSV), the parainfluenza viruses and the enteroviruses. RSV, parainfluenza virus types 1 and 3, and the adenoviruses caused infection mainly in young children under 3 years of age, while the influenza viruses and Mycoplasma pneumoniae caused infection more frequently in older, school-aged children. There was a strong clinical association of bronchiolitis with RSV and the rhinoviruses, of laryngitis or laryngotracheobronchitis with parainfluenza virus types 1 and 2, of pneumonia with Mycoplasma pneumoniae, and of upper respiratory infection or "flu" with the influenza viruses. The significance of some of these findings is discussed. PMID- 6269480 TI - In vitro antimicrobial activity of ceftizoxime against glucose-nonfermentative gram-negative rods. AB - Ceftizoxime, a new cephalosporin, was active against Pseudomonas cepacia, Flavobacterium meningosepticum, Alcaligenes faecalis, and Acinetobacter calcoaceticus and was more potent against Pseudomonas aeruginosa and Pseudomonas putida than was carbenicillin. PMID- 6269481 TI - In vitro comparison of N-formimidoyl thienamycin, piperacillin, cefotaxime, and cefoperazone. AB - The antibacterial activity of N-formimidoyl thienamycin was compared with those of cefotaxime, cefoperazone, and piperacillin against 536 clinical aerobic isolates. PMID- 6269482 TI - Antiherpesviral and anticellular effects of 1-beta-D-arabinofuranosyl-E-5-(2 halogenovinyl) uracils. AB - 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl) uracil (BV-ara-U) and 1-beta-D arabinofuranosyl-E-5-(2-chlorovinyl)uracil (CV-ara-U) were tested for their anti herpesviral activity in virus rating method, a plaque reduction method, and a virus yield reduction method, using human embryonic lung fibroblast (HEL-F) cells, At a concentration as low as 0.1 microgram/ml, both drugs exerted a marked inhibitory effect on the development of cytopathogenic effect induced by herpes simplex virus type 1 (HSV-1) infection and on the multiplication and plaque formation of HSV-1. Neither BV-ara-U nor CV-ara-U was significantly active against HSV type 2 (HSV-2). They scarcely inhibited growth of HEL-F cells, mouse L, and murine leukemia cells. Compared with 1-beta-D-arabinofuranosylthymine and 5-iodo-deoxyuridine, BV-ara-U and CV-ara-U were more than 10 times as active against HSV-1 and much less active against HSV-2. BV-ara-U was as active as E-5 (2-bromovinyl)-2'-deoxyuridine against HSV-1 and less inhibitory to growth of HEL F cells. Cellular deoxyribonucleic acid synthesis was not significantly influenced by the new derivatives of arabinosyluracil, even at a concentration as high as 300 microgram/ml. The derivatives showed extremely marked inhibition of deoxyribonucleic acid synthesis in HSV-1-infected cells, whereas their inhibitory effect on deoxyribonucleic acid synthesis in HSV-2-infected cells was much lower than that in HSV-1-infected cells. These findings indicate that BV-ara-U and CV ara-U are selectively inhibitory to HSV-1 multiplication. PMID- 6269483 TI - Sensitive bioassay for ketoconazole in serum and cerebrospinal fluid. AB - Ketoconazole is a broad-spectrum antifungal agent which appears promising for treatment of a variety of systemic mycoses. Pharmacokinetic studies are limited due to a lack of readily available methods for quantitation of ketoconazole in serum or cerebrospinal fluid. We developed a rapid, simple bioassay for measurement of ketoconazole alone or in the presence of therapeutic levels of amphotericin B, using an agar diffusion assay incorporating Candida pseudotropicalis. Pairs of 8-mm wells cut in the seeded assay medium were filled with four duplicate ketoconazole standards and duplicate patient specimens. Zones of inhibition were visible after 7 to 8 h of incubation, but were most easily measured after overnight growth. The assay allowed determinations of serum ketoconazole levels as low as 0.3 microgram/ml with a 4.4% coefficient of variation. Thirty-five serum samples from patients receiving the drug were assayed by this method, and the results were compared with the Coccidioides immitis endospore assay. The correlation coefficient between the assays was 0.90. This assay allows any microbiology laboratory to easily and safely determine ketoconazole levels in serum or cerebrospinal fluid. PMID- 6269484 TI - Bactericidal activity of cefoperazone with CP-45,899 against large inocula of beta-lactamase-producing Haemophilus influenzae. AB - Bactericidal activity of cefoperazone, alone and in combination with the beta lactamase inhibitor CP-45,899, was tested against inocula of 10(7) colony-forming units of beta-lactamase-producing isolates of Haemophilus influenzae type b per ml. Of 19 strains tested, 10 required greater than or equal to 64 microgram of cefoperazone per ml for killing, whereas no strains were killed by less than 64 microgram of CP-45,899 per ml. Synergy occurred with the combination of 4 microgram of each agent per ml against 9 of the 10 cefoperazone-resistant strains. PMID- 6269485 TI - Heterogeneity of action of mechanisms among antimycotic imidazoles. AB - The three imidazole antimycotics clotrimazole, miconazole, and ketoconazole all inhibit the demethylation of lanosterol to ergosterol, resulting in inhibition of growth of Saccharomyces cerevisiae; this is a fungistatic action. At higher concentrations clotrimazole and miconazole are fungicidal, whereas ketoconazole is not. The fungicidal action reflects direct membrane damage by the imidazoles. Evidence for this is that ketoconazole is markedly less active than the other imidazoles in its ability to allow methylene blue entry into cells and to disrupt liposome model membranes. The possible clinical significance of these findings is discussed. PMID- 6269486 TI - New plasmid-mediated aminoglycoside adenylyltransferase of broad substrate range that adenylylates amikacin. AB - The same aminoglycoside 2"-adenylyltransferase was isolated from four gram negative species which were among a random group of gentamicin-resistant isolates from the same hospital. The enzyme was partially purified from a crude extract which also contained a second modifying enzyme identified as APH(3')-I. The substrate range of the new aminoglycoside 2"-adenylyltransferase included the newer aminoglycosides sisomicin and amikacin, but showed much-reduced activity against gentamicins C2 and Cla. The pH optimum was 7.8 to 8.0 for every substrate, and the molecular weight of the enzyme molecule was estimated at approximately 29,000. Genetic experiments clearly established that both enzymes were expressed by a conjugative plasmid. PMID- 6269487 TI - In vivo activity of ceftriaxone (Ro 13-9904), a new broad-spectrum semisynthetic cephalosporin. AB - Ceftriaxone (Ro 13-9904) was compared with other newer beta-lactam antibiotics for activity in experimental infections of mice with Enterobacteriaceae, Haemophilus influenzae, Pseudomonas aeruginosa, and gram-positive bacteria. Overall, ceftriaxone was equal or superior to cefotaxime and cefoperazone against systemic infections. All three drugs were highly potent against most organisms but were considerably less active against P. aeruginosa. However, ceftriaxone tended to be more active than the other two agents against 8 of the 10 P. aeruginosa strains tested. Ceftriaxone, cefmenoxime (SCE 1365), and moxalactam were all highly active against systemic infections with 16 strains of Enterobacteriaceae, whereas ceftriaxone was more active against infections with two strains of streptococci. When the drugs were administered at various time intervals before infection, ceftriaxone was superior to cefotaxime, cefmenoxime, and moxalactam. This suggested that ceftriaxone might be eliminated from mice more slowly than the other drugs. In the case of cefotaxime, this was directly confirmed by microbiological assays of plasma samples. In a murine meningitis model induced by Klebsiella pneumoniae or Streptococcus pneumoniae, ceftriaxone was more active than ampicillin or cefotaxime. Ceftriaxone was more active than ampicillin, cefotaxime, piperacillin, cefamandole, or carbenicillin in a pneumococcal, pneumonia model in mice. These studies indicate that ceftriaxone is a potent, broad-spectrum cephalosporin with unusual pharmacokinetic properties. PMID- 6269488 TI - Beta-lactamase stability and antibacterial activity of cefmenoxime (SCE-1365), a novel cephalosporin. AB - Cefmenoxime, a new cephalosporin antibiotic, has been shown to be stable to a Staphylococcus aureus penicillinase and R plasmid-mediated type I and type IV penicillinases. It was also resistant to hydrolysis by most cephalosporinases, but was susceptible to hydrolysis by a Proteus vulgaris beta-lactamase. Cefmenoxime was active against cephaloridine-resistant species, except Pseudomonas aeruginosa, which was moderately resistant to cefmenoxime. Cefmenoxime was an inducer of P. vulgaris beta-lactamase biosynthesis, but 1 microgram or more of the drug per ml, which inhibits most of the clinical isolates of P. vulgaris, was required for the production of detectable amounts of the enzyme. Cefmenoxime was a strong competitive inhibitor of beta-lactamases of Enterobacter cloacae, Citrobacter freundii, P. aeruginosa, and Serratia marcescens, but it did not inhibit penicillinases in spite of its resistance to hydrolysis. PMID- 6269489 TI - Immunological properties of beta-lactamases that hydrolyze cefuroxime and cefotaxime. AB - Antiserum against purified beta-lactamase from Proteus vulgaris GN7919 cross reacted with beta-lactamases produced by strains of Pseudomonas cepacia in a neutralization test. Anti-P. cepacia beta-lactamase serum, however, did not show any cross-reactions with P. vulgaris beta-lactamases. Each of these enzymes can hydrolyze cefuroxime and cefotaxime. PMID- 6269490 TI - Efficacy of acyclovir against mouse cytomegalovirus in vivo. AB - Acyclovir reduced mortality and organ virus titers in mice inoculated intraperitoneally with 10 50% lethal doses of mouse cytomegalovirus. This susceptibility to acyclovir of a herpesvirus which lacks thymidine kinase is surprising. Alternative phosphorylating enzymes may account for this susceptibility. PMID- 6269492 TI - The environment of the sulfhydryl group in human plasma albumin as determined by spin labeling. PMID- 6269491 TI - Serum substitute in epithelial cell culture media: nonfat dry milk filtrate. AB - A number of milk types and milk fractions were investigated as possible substitutes for serum in cell culture media. A filtrate of reconstituted nonfat dry milk showed promise. Culture fluids containing 5% of the nonfat dry milk filtrate were used to propagate primary and continuous cell cultures, and the cell growth from these cultures was compared with that of cells grown in a serum containing medium. The nonfat dry milk filtrate-supplemented medium supported the growth of all epithelial cells tested, but two fibroblast-type cultures failed to replicate. Cells grown in the medium containing the milk filtrate grew slowly for 2 to 3 days and then propagated to confluency in 6 to 8 days. Viable cell counts of 9 days were comparable to those of serum-grown cells that had been propagated for 7 days. Cells grown in the milk filtrate could be split 1 to 4 when subcultures were prepared. Cell growth could be stimulated by refeeding on days 2 to 3 or by the addition of 30 microM 2-mercaptoethanol to the growth medium. Virus susceptibility and titer comparisons with poliovirus 1, coxsackievirus B2, echovirus 7, and herpes simplex virus indicated that approximately the same data were obtained when either the nonfat dry milk filtrate-treated or the serum treated cells were studied. The nonfat dry milk filtrate is inexpensive, is easily prepared, and is a substitute for serum in epithelial cell culture media. PMID- 6269493 TI - Biosynthesis of bacterial glycogen: purification and characterization of ADPglucose pyrophosphorylase with modified regulatory properties from Escherichia coli B mutant CL1136-504. PMID- 6269494 TI - Cytochrome c reduction by semiquinone radicals can be indirectly inhibited by superoxide dismutase. PMID- 6269495 TI - The respiratory system of Pseudomonas putida: participation of cytochromes in electron transport. PMID- 6269496 TI - Partial purification and properties of diacylglycerol kinase from rat liver cytosol. PMID- 6269497 TI - Cholera-toxin-dependent ADP-ribosylation of the adenylate cyclase regulatory protein in turkey erythrocyte membranes. PMID- 6269498 TI - A comparison of solution properties of cholesterol and 25-hydroxycholesterol. PMID- 6269499 TI - An unusual transformation of a common wart in a child. PMID- 6269500 TI - Progressive nodular histiocytoma. AB - Progressive nodular histiocytoma is a clinically distinct variant in the general group of normolipemic histiocytic proliferations. Its cardinal feature is the presence of two different lesions--a superficial yellow-brown papule and a deep nodule. We describe herein a 29-year-old man with such lesions. Histologically, a variety of fibrous and cellular patterns were seen, mimicking the wide spectrum of findings in ordinary dermatofibromas. On ultrastructural examination, the most striking feature of the preponderant cell was lipid phagocytosis. PMID- 6269501 TI - Cutaneous syndromes of non-X histiocytosis. A review of the macrophage-histiocyte diseases of the skin. AB - The bone marrow and blood monocytes are precursor cells to the macrophage histiocyte, the Langerhans cell, the indeterminate cell, the interdigitating cell, and the dendritic cell in the thymus, lymph node, and skin. While there are many histologic and functional similarities in these cell types, some differences do occur. A notable difference is the minimal phagocytosis by the Langerhans cell and the histiocytosis X cell. Non-X histiocytosis is represented by a series of cutaneous disease patterns characterized by localized, nonaggressive, histioxanthomatous skin and mucous membrane lesions, with a tendency to self heal, Eruptive histiocytoma, juvenile xanthogranuloma, reticulohistiocytoma cutis, papular xanthoma, necrobiotic xanthogranuloma with paraproteinemia, and xanthoma disseminatum are cutaneous patterns of non-X histiocytosis that suggest the possibility of at least two patterns of peripheral macrophage differentiation and pathologic change. PMID- 6269502 TI - Concentrations of SP1 and beta-hCG in serum and cerebrospinal fluid and concentrations of hCG in urine in patients with trophoblastic tumour. AB - Using immunological techniques urinary hCG, pregnancy-specific beta 1 glycoprotein (SP1) and beta-subunit of hCG (beta-hCG) levels were measured in the serum and cerebrospinal fluid of patients with trophoblastic tumours. After removal of hydatidiform moles, urinary hCG, beta-hCG and SP1 levels were similar, but SP1 levels tended to exceed serum beta-hCG levels. SP1 usually disappeared first. In patients with metastatic choriocarcinoma, SP1 levels appeared to be lower than beta-hCG values in serum and cerebrospinal fluid, but urinary hCG, beta-hCG and SP1 concentrations all decreased during chemotherapy. Measurements of SP1 levels may well be useful in the monitoring of patients being treated for trophoblastic tumours. PMID- 6269503 TI - Cyclic nucleotides and cellular kinetics in normal and abnormal human trophoblastic tissue. AB - The ability to synthesize DNA and the cell cycle of normal trophoblastic cells and the trophoblastic cells of hydatidiform moles and invasive moles were studied by the autoradiographic technique. Compared with normal trophoblast, hydatidiform moles or invasive moles had a higher ability to synthesize DNA. cAMP tended to inhibit DNA synthesis in normal and molar tissue, whereas cGMP tended to promote it. The cell cycle time for each type of trophoblastic tissue was roughly 15 h; however, as compared to normal trophoblast, the hydatidiform or invasive moles had a longer S phase and a shorter G1 phase. PMID- 6269504 TI - [Congenital mesoblastic nephroma. Study of five cases and review of literature (author's transl)]. PMID- 6269505 TI - Effects of ouabain on spermatozoan function: a review. AB - The cardiac glycoside, ouabain, exerts its influence on spermatozoa by binding to and inhibiting Mg2+-activated Na+, K+-dependent ATPase that is located in the midpiece-tail membranes. Ouabain decreased intracellular potassium, increased intracellular sodium, and produced a biphasic and time-dependent effect on motility--stimulation at low concentrations and inhibition at high concentrations. The motility depression consisted of decreases in numbers of motile cells, percent progressive motility, beat frequency, and amplitude. Species differences and maturational age of the sperm cells were reflected in the degree of the ouabain effect and also the distribution of the ouabain-sensitive enzyme. The presence of this enzyme in spermatozoan membranes contributes significantly to regulation of sperm cell function through modulation of cationic fluxes which in "conventional" cell types influence their excitability. PMID- 6269506 TI - [Focus of amebiasis in a psychiatric hospital in the east of France]. AB - At the occasion of the discovery of an amoebiasis focus in a psychiatric hospital (36,2 % of the patients were Entamoeba histolytica carriers), the authors insist on the importance of systematical and continued coprological controls. They observe that the two means of fight used together, the environment and the mass treatment, have strongly limited the propagation of parasitosis. By this way they note efficiency of the association of the medicinal polyvalent and contact amoebicides. PMID- 6269507 TI - Manifestation of latent alpha-excitatory response in the canine tracheal smooth muscle preparation--relation to basal tone. AB - Alpha-adrenergic contractile response of the tracheal smooth muscle preparation isolated from young adult dogs was investigated. When the basal tone of the preparation was elevated by spasmogens, methacholine, K+, etc., in the presence of 1 microM propranolol, norepinephrine and phenylephrine caused contraction of the preparation. Isoproterenol did not. The contraction was specifically antagonized by phentolamine. The height of contraction caused by alpha-stimulants depended on the height of basal tone. The relationship of them was essentially the same whether methacholine on K+ was used as spasmogen, and if the Ca ion concentration in Krebs' solution was reduced to 0.1 mM. It was concluded that the tracheal smooth muscle of young adult dogs which is usually insensitive to alpha stimulants responds to them when the basal tone is elevated by spasmogens, and it was suggested that an elevated intracellular free-Ca ion level contributed to this phenomenon. PMID- 6269508 TI - The effect of neuromuscular blocking agents on the acetylcholine receptors of different skeletal muscles. AB - The comparative sensitivity of acetylcholine receptors of different skeletal muscles--m. masseter, m. gastrocnemius, m. triceps brachii, mm. obliquus et transversus abdominis, mm. intercostales, m. phrenicus to neuromuscular blocking agents was investigated. Experiments were performed on cats anesthetized with urethane (600 mg/kg, i.v.) and chloralose (70 mg/kg, i.v.). Muscle action potentials evoked by electrical stimulation of motor nerves were recorded. Derivatives of alpha-truxillic acid--anatruxonium and cyclobutonium, steroidal neuromuscular blocking agents--pancuronium and pipecurium, decamethonium and succinylcholine and their N-adamantyl analogues--decadonium and diadonium respectively, as well as tubocurarine chloride were tested. It was shown that the succession of relaxation of different skeletal muscles induced by the neuromuscular blocking agents of different chemical structure is variable. PMID- 6269509 TI - The effects of imidazole on neuromuscular transmission and on synaptosomal calcium uptake in the rat. AB - The action of imidazole on neuromuscular transmission has been studied on the rat phrenic nerve-diaphragm preparation, and on the uptake of 45Ca on pinched-off presynaptic nerve terminals (synaptosomes) from rat brain. Imidazole (0.5--5 mM) reversibly increased the quantum content of evoked end-plate potentials and the mean amplitude of miniature end-plate potentials in preparations in which transmission was partially blocked with high Mg2+ and/or low Ca2+ concentrations. In solutions with a low Ca2+ concentration imidazole caused a smaller effect on the mean quantal content of evoked end-plate potentials. Imidazole also reversibly increased the amplitude of end-plate potentials in which transmission was blocked with tubocurarine. Imidazole decreased the frequency of miniature end plate potentials in unstimulated preparations. Imidazole was devoid of effect on the compound action potential of the frog-sciatic nerve. Synaptosomes have been used to test the action of imidazole on 45Ca uptake. The substance (0.5--4 mM) enhanced the potassium stimulated uptake of 45Ca but had little or no effect on unstimulated synaptosomes. It is concluded that the excitatory effect of imidazole on the evoked release of the transmitter can be interpreted in terms of the increased calcium influx which it produced. The depressing effect on the frequency of miniature end-plate potentials is discussed in relation to the mechanisms that regulate the level of intracellular calcium. PMID- 6269510 TI - Treatment of small cell lung cancer - 1981. PMID- 6269511 TI - [Febrile mononucleosis after cardiac surgery. A clinical study of 15 cases of cytomegalovirus infection]. PMID- 6269512 TI - Relationship of internal cyclic AMP levels, rates of protein synthesis and mucor dimorphism. AB - Changes in the intracellular pools of cyclic AMP and specific rates of protein synthesis have been described as correlates of the yeast-to-hypha conversion in Mucor racemosis. A further examination of the relationship between these physiological parameters and the cellular morphogenesis was conducted in the present study. The levels of intracellular cyclic AMP consistently varied as a function of the cell morphology rather than the CO2 tension, oxygen tension or growth rate. The specific rate of protein synthesis failed to change during a N2 to-air-induced yeast-to-hypha transition. Previously reported changes in this parameter during CO2-to-air- and CO2-to-N2-induced yeast-to-hypha shifts may be a consequence of growth rate changes rather than development per se. PMID- 6269513 TI - Homoserine and threonine pools of borrelidin resistant Saccharomyces cerevisiae mutants with an altered aspartokinase. PMID- 6269514 TI - Hereditary of the three enzyme systems EsD, Gt and GLO in the Polish population. The family studies and mother/child combinations. AB - Hereditary of the three enzyme systems EsD, Gt and GLO was studied in families and mother/child combinations. EsD types were determined in 88 families with 197 children and 1813 mother/child combinations. Gt types were studied in 78 families with 174 children and 114 mothers with one child. GLO types were determined in 82 families with 180 children and 298 mother/child pairs. The segregation in the different family combinations is in accordance with the simple formal model of two alleles at the autosomal loci. PMID- 6269515 TI - Paget's disease of the penis and adjacent skin: its association with fatal sweat gland carcinoma. PMID- 6269516 TI - 'Rhabdoid' Wilms' tumor: an ultrastructural study. AB - We studied a 5-week-old infant who had a "rhabdoid" Wilms' tumor. Ultrastructural studies disclosed aggregates of cytoplasmic filaments that seemed to correspond with the eosinophilic cytoplasmic bodies seen by light microscopy, but did not uncover evidence of rhabdomyoblastic differentiation. The histogenesis of this subtype was not established, but origin from the metanephric blastema could not be ruled out. PMID- 6269517 TI - Relationship between lead concentration in blood and the activities of erythrocyte pyrimidine 5'-nucleotidase and delta-aminolevulinate dehydratase in the mice exposed to lead. AB - The relationship between the activities of both pyrimidine 5'-nucleotidase (Py5N) and delta-aminolevulinate dehydratase (ALA-D) in erythrocytes and the concentration of lead in blood was investigated in the mice which were given ad libitum a drinking water containing lead of 10 to 500 ppm, for 30 days. From these results, it was demonstrated that the erythrocyte Py5N activity is inhibited by lead and its activity level is negatively correlated with the concentration of lead in blood (r = -0.78). In addition, it was suggested that the erythrocyte Py5N activity is a better indicator in the exposure to relatively high lead concentration while the ALA-D is a more sensitive indicator for evaluating the lead exposure of low and moderate levels. PMID- 6269518 TI - [Effect of hydrocortisone on alpha-glycerophosphate dehydrogenase activity in KOX 1 and mouse glioblastoma EPNT-5 cells]. AB - A comparative cytochemical investigation for alpha-glycerophosphate dehydrogenase (alpha-GPhD) activity in transplanted cellular line of mouse glioblastoma (EPNT 5) and KOX-1 was performed under normal conditions and under hydrocortisone effect. In glioblastoma EPNT-5 cells a high alpha-GPhD activity was revealed. The enzymatic activity was found to correspond to the dynamics of cell multiplication. Under the effect of hydrocortisone, alpha-GPhD activity demonstrated a two-fold increase, while alpha-GPhD activity in KOX-1 cells was very low, and hydrocortisone did not induce its increase. The data obtained supported the view on the glial nature of the transplanted cpHT-5 line and demonstrated that the glial elements preserved their specific peculiarities at a prolonged cultivation. PMID- 6269519 TI - [Contribution of computerized tomography to the diagnosis and postoperative study of sellar tumors]. AB - The computerized tomography (C.T.) of 18 patients with sellar tumours were analysed. The C.T. made before surgery in 6 cases was positive in 3 and the type of tumour suggested by C.T. was confirmed in 3. Twelve patients had a C.T. investigation after surgery and the examination suggest recurrent tumour in 5. Two of these were re-operated. One patients with cholesteatoma had the recurrent tumour verified by surgery and the other, with a pituitary adenoma during re operation was noted only cicatricial tissue at sellar region. PMID- 6269520 TI - [Neurobrucellosis: report of 3 cases]. AB - Three cases of probable neurobrucellosis are reported. The diagnosis was made on the basis of immunological tests. Two patients with a clinical picture of meningomyelitis showed a definitive clinical improvement under tetracycline and streptomycin therapy. The immunological reactions found in the record case were even more positive in the spinal fluid than in the blood. In the case 3 with a clinical presentation of cerebral hemorrhage the histopathological studies demonstrated non specific chronic leptomeningitis and local hemorrhages in the caudate nucleus bilaterally. The diagnose and treatment of neurobrucellosis are discussed, stressing the importance of an early therapy. PMID- 6269521 TI - Regional difference in susceptibility to damage of vestibulo-semicircular canals in experimental labyrinthine lesion. AB - In the study on regional difference in susceptibility to damage of vestibulo semicircular canals upon causing labyrinthine lesion by four different procedures, namely, by intracranial approach, through the middle ear, through the facial nerve and by means of experimental endolymphatic hydrops, the following results were obtained. 1. The crista of posterior semicircular canal among the semicircular canals and the macula of the saccule within the vestibule were most susceptible to impairment. In other words, the most susceptible region was the so called pars inferior. In regard to the impairment of the cupulas, the posterior semicircular canal was the most susceptible region. 2. Recovery from markedly reduced caloric nystagmus within a short period so as to see provocation of caloric nystagmus may result from the reconstruction of the cupulas and the normalization of vacuole-like findings of the sensory epithelium. PMID- 6269522 TI - Diagnosis of olfactory disturbance. AB - The methods of examination for dysosmia were reported. One thousand four hundred cases of dysosmia were treated in the last 5 years by the following examinations: 1) Olfactory acuity (detected and recognized) threshold test using T & T olfactometer. 2) Blast injection method using an applicator permeated with Alinamin solution. 3) Intravenous olfaction test using Alinamin solution. 4) Endoscopic observation of olfactory mucosa using an endoscope. The parts of lesions were diagnosed and various treatments were selected based on the results of these examinations. Nose drops of adrenocortical hormone were mainly used, while medications of peripheral vasodilator or medications for reducing of the mucosa were used in some cases. Many cases were effectively improved by the nose drops of adrenocortical hormone in Japanese patients. More than 70% of total cases were improved by these treatments. PMID- 6269523 TI - Adeno-viral kerato conjunctivitis. AB - In summer, 1976 an epidemic of Kerato Conjunctivitis commenced in Melbourne, Australia. A total of 422 patients was studied in the adeno-viral clinic at the Royal Victorian Eye and Ear Hospital, Melbourne, from 1976 to 1979. Most patients were referred from the Casualty Department of the hospital, but others came from private practice. A total of 72 cases were adeno-viral with positive cultures. Types 8 and 19 predominated, but sporadic cases of types 1, 3, 4 and 7 were also isolated. Herpes Simplex type 1 was positive in 13 patients. The hospital staff were involved in spread of adeno-virus type 8. Six patients contracted Kerato Conjunctivitis following removal of corneal foreign bodies from the casualty ward, and several patients contracted epidemic Kerato-Conjunctivitis after beta irradiation post-pterygium surgery. These latter two methods of infection have not been reported before. Treatment and prevention is discussed. PMID- 6269525 TI - Effect of electroconvulsive shock on beta-endorphin immunoreactivity of rat brain, pituitary gland, and plasma. PMID- 6269524 TI - Repeated intracerebroventricular injections of ACTH1-24 in rats with hippocampal lesions. PMID- 6269526 TI - Extinction of a conditioned taste aversion in young, mid-aged, and aged C57/BL6 mice. PMID- 6269527 TI - Assessment of vasoactive metabolites released from the isolated guinea pig during heart hypoxia and beta-adrenergic stimulation. AB - Two isolated guinea pig hearts (H1, H2) were perfused in series in order to bioassay in the recipient heart (H2) the release of vasoactive metabolites. Due to an effective reoxygenation system transit time between H1 and H2 as only 20 sec. Hypoxic perfusion (30% O2) of H1 caused relaxation of the coronary vessels of H2, and this effect could be completely abolished by adenosine deaminase. Similar results were obtained when H1 was stimulated by isoproterenol while H2 was protected by propranolol. From our findings it is concluded that adenosine is the primary vasodilating substance released by the heart into the coronary circulation. PMID- 6269528 TI - The interaction of calcium and cAMP and the relationship to ventricular vulnerability. PMID- 6269530 TI - Role of carbohydrates in the diet of industrialised countries. PMID- 6269529 TI - Problems of mineral supply in industrialized countries. AB - The main nutritional problems, related to mineral supply, can be seen in two respects: (1) Minerals with sufficiently known parameters, so that RDA have been generally established. Basic knowledge is advanced, open questions are connected with insufficient (Fe, I, Zn, Cu), or excessive (Na) intake, or with imbalances. (2) Metals, occurring in food and needed in metabolism in trace amounts. exact RDA have not been established due to lack in basic knowledge. Open questions are conncected with analytics, bioavailability, requirements, mode of action, effects of deficiency and excess in relation to homeostasis and disease, and in some cases with essentiality. Nutritional problems exist in (a) differences in trace element contents between mother's milk and infant milk formula; (b) the reduction of trace element contents in modern diet due to changing food habits and food processing and refining; (c) increasing information about protective or harmful influences of trace elements upon chronic degenerative diseases: (d) toxicology, including cancerogenicity of trace metals, and (e) relations to pharmaceuticals like contraceptives or to fiber. PMID- 6269531 TI - Refined foods. PMID- 6269532 TI - Procollagen type III N-terminal endopeptidase in fibroblast culture. AB - A peptidase activity capable of excising in a single fragment the N-terminal extension of the precursor of collagen type III (p-N-collagen type III) was observed in calf tendon fibroblast culture medium. A new procedure was developed for detecting this peptidase (p-N-collagen type III peptidase). It is based on the use of 14C-labelled p-N-collagen type III obtained by carboxymethylation of the half-cystine residues with iodo-[14C]acetamide. The released labelled N terminal extension is soluble in 27% (v/v) ethanol, whereas the uncleaved substrate and the collagen are precipitated under these conditions. The endopeptidase nature of p-N-collagen type III peptidase is supported by the similarity in molecular weight of the product of cleavage of p-N-collagen III by the enzyme to those obtained by cleavage with bacterial collagenase. An apparent Km of 0.3 X 10(-6)M was established. The pH optimum of p-N-collagen type III peptidase is similar to that of p-N-collagen type I peptidase, i.e. about 7.5. Both peptidases are inhibited by dithiothreitol and by Cu2+ and Zn2+, but not by other bivalent ions. p-N-collagen type III peptidase does not cleave p-N-collagen I or p-N-gelatin I. Partial purification of p-N-collagen type III peptidase from fibroblast culture medium was performed by sieve chromatography on Ultrogel AcA 34 to yield two peaks of activity, of mol.wts. 170000 and 100000. Part of the activity was retained on affinity chromatography on concanavalin A--Sepharose. Studied as a function of the age of the culture, p-N-collagen type III peptidase activity produced by tendon fibroblasts parallels that of p-N-collagen type I peptidase and collagen synthesis. PMID- 6269533 TI - Light-mediated activation of stromal sedoheptulose bisphosphatase. AB - When isolated wheat (Triticum aestivum) chloroplasts were illuminated, the activity of sedoheptulose bisphosphatase increased severalfold. The rate of activation was limited by the size of the carbon pool, and experiments with a partially purified enzyme preparation showed that the degree of reductive activation of the enzyme is governed by the concentration of its substrate. PMID- 6269534 TI - Methylation of nuclear DNA in Physarum polycephalum. AB - The restriction endonucleases HpaII and HhaI, whose action is inhibited by the presence of methylated base analogues at the recognition sequences in the DNA substrate, were used to investigate the distribution of 5-methylcytosine in nuclear DNA from Physarum polycephalum. Physarum DNA is digested into two fractions by these enzymes: a low-molecular-weight (M--) compartment comprising 80% of the DNA, and a high-molecular-weight (M+) compartment containing 20% of the DNA. The DNA fraction showing resistance to digestion by restriction endonuclease HpaII is cleaved by its isoschizomer MspI, indicating that methylated endonuclease-HpaII-specific sites are present in M + DNA. Additional properties of sequences in the M+ compartment were investigated. PMID- 6269535 TI - The role of membrane-bound 5'-nucleotidase in the transport and utilization of nicotinic acid ribonucleotide. PMID- 6269536 TI - The effects of epinephrine on guinea pig placental glycogen metabolism and on cellular cyclic AMP. PMID- 6269537 TI - Isolation of sarcolemma from newborn rabbit cardiac muscle. PMID- 6269538 TI - Human mitochondrial electron transport chain: assay of succinate: cytochrome c reductase in leukocytes, platelets and cultured fibroblasts. PMID- 6269539 TI - RNA polymerase and protein kinase activities of aortic nuclei during early atherogenesis. PMID- 6269540 TI - Fructose 1,6-bisphosphatase in rat liver cytosol: activation after glucagon treatment in vivo and inhibition by fructose 2,6-bisphosphate in vitro. PMID- 6269541 TI - Serotonin (5-hydroxytryptamine): a possible regulator of glycogenolysis in perfused muscle segments of Ascaris suum. PMID- 6269542 TI - beta-Endorphin: replacement of glutamic acid in position 8 by glutamine increases analgesic potency and opiate receptor-binding activity. PMID- 6269543 TI - Structure of lipoprotein (a) studied by spin-labeling. PMID- 6269544 TI - The single-strands of yeast autonomously replicating DNA segments are not recognized as origins of replication by Escherichia coli DNA replication proteins. PMID- 6269545 TI - Detection by electron spin resonance of an exchange-coupled Cob(II)alamin...free radical pair species generated by anaerobic photolysis of polycrystalline adenosylcobalamin. PMID- 6269547 TI - Difference in putrescine transport in undifferentiated versus differentiated mouse NB-15 neuroblastoma cells. PMID- 6269546 TI - Glycosylation of cell surface receptors: tunicamycin treatment decreases insulin and growth hormone binding to different levels in cultured lymphocytes. PMID- 6269548 TI - In vitro transcription of cloned yeast ribosomal DNA by yeast RNA polymerase A. PMID- 6269549 TI - On a possible mechanism of action of ascorbic acid: formation of ionic bonds with biological molecules. PMID- 6269550 TI - Inhibitory action of guanosine 3', 5'-monophosphate on thrombin-induced phosphatidylinositol turnover and protein phosphorylation in human platelets. PMID- 6269551 TI - Structural polypeptide composition of a murine myeloma (MOPC-315) type C retrovirus. PMID- 6269552 TI - Chronic exposure to a 60-Hz electric field: effects on synaptic transmission and peripheral nerve function in the rat. AB - Several reports have suggested that the nervous system can be affected by exposure to electric fields and that these effects may have detrimental health consequences for the exposed organism. The purpose of this study was to investigate the effects of chronic (30-day) exposure of rats to a 60Hz, 100-kV/m electric field on synaptic transmission and peripheral-nerve function. One hundred forty-four rats, housed in individual polycarbonate cages were exposed to uniform, vertical, 60-Hz electric fields in a system free of corona discharge and ozone formation and in which the animals did not receive spark discharges or other shocks during exposure. Following 30 days of exposure to the electric field, superior cervical sympathetic ganglia, vagus and sciatic nerves were removed from rats anesthetized with urethan, placed in a temperature-controlled chamber, and superfused with a modified mammalian Ringer's solution equilibrated with 95% O2 and 5% CO2. Several measures and tests were used to characterize synaptic transmission and peripheral-nerve function. These included amplitude, area, and configuration of the postsynaptic or whole-nerve compound-action potential; conduction velocity; accommodation; refractory period; strength duration curves; conditioning-test (C-T) response, frequency response; post tetanic response; and high-frequency-induced fatigue. The results of a series of neurophysiologic tests and measurements indicate that only synaptic transmission is significantly and consistently affected by chronic (30-day) exposure to a 60 Hz, 100-kV/m electric field. Specifically, and increase in synaptic excitability was detected in replicated measurements of the C-T response ratio. In addition, there are trends in other data that can be interpreted to suggest a generalized increase in neuronal excitability in exposed animals. PMID- 6269553 TI - Biological effects of oscillating electric fields: role of voltage-sensitive ion channels. AB - An alternating component of potential across the membrane of an excitable cell may change the membrane conductance by interacting with the voltage-sensing charged groups of the protein macromolecules that form voltage-sensitive ion channels. Because the probability than a voltage sensor is in a given state is a highly nonlinear function of the applied electric field, the average occupancy of a particular state will change in an oscillating electric field of sufficient magnitude. This "rectification" at the level of the voltage sensors could results in conformational changes (gating) that would modify channel conductance. A simplified two-state model is examined where the relaxation time of the voltage sensor is assumed to be considerably faster than the fastest changes of ionic conductance. Significant changes in the occupancy of voltage sensor states in response to an applied oscillating electric field are predicted by the model. PMID- 6269554 TI - [The renin-angiotensin system and its inhibition (author's transl)]. AB - The recent development of several inhibitors of the renin-angiotensin system has perfected our knowledge of the part played by this system in the control of physiological and pathological arterial pressure. Peptides inhibiting angiotensin II, such as Sar1, Ala8 angiotensin II, block the peripheral effects of angiotensin on vascular renal and adrenal receptors. Inhibition of the conversion enzyme, notably with captopril, prevents the formation of angiotensin II from angiotensin I and also results in accumulation of a vasodilator and natriuretic peptide: bradykinin. Finally, it is now possible to inhibit more specifically the reaction of renin with its substrate, angiotensinogen, by using pepstatin or its derivatives, or peptide analogues of the substrate. The use of these inhibitors, especially captopril (so far the most studied), has made it clear that renin plays a part in experimental and human essential hypertension and participates in the control of arterial blood pressure in subjects with normal sodium intake. PMID- 6269555 TI - [Pharmacological effects of captopril]. PMID- 6269556 TI - [Preventive effect of captopril on the development of genetic hypertension in SHR rats (author's transl)]. AB - Captopril, an inhibitor of the angiotensin-converting enzyme, is very effective in preventing the development of genetic hypertension in SHR rats. This effect results from early, overall lowering of local vascular resistances and, consequently, suppression of the age-related increase in total peripheral resistance. Contrary to that of dihydralazine and atenolol, it persists for up to 12 weeks after the drug is discontinued. Captopril may act by inhibiting the angiotensin-converting enzyme present in the vascular wall, with subsequent temporary arrest of the vascular lesions associated with progressive genetic hypertension. PMID- 6269557 TI - [Treatment of severe arterial hypertension with captopril (SQ 14.225) (author's transl)]. AB - Captopril, an inhibitor of the angiotensin-converting enzyme, was administered for 9 to 13 months to 11 patients with severe arterial hypertension and/or hypertension resistant to conventional treatments. The drug had to be discontinued in 2 patients on account of skin rash or peripheral neuropathy. In the remaining 9 patients, return of blood pressure to normal levels was obtained with combined captopril and diuretic treatment, except in one case where captopril alone proved sufficient. The anti-hypertensive effect developed over several weeks. No rebound phenomenon was observed after temporary arrest of captopril. Positive correlation was noted between the fall in blood pressure induced by the first dose of captopril and the patients' initial plasma renin activity. Captopril appears to be of considerable interest for the treatment of severe hypertension, even when it is associated with renal insufficiency. PMID- 6269559 TI - [Pathology of the neural crest (author's transl)]. PMID- 6269558 TI - [Clinical, haemodynamic and biochemical effects of angiotensin-converting enzyme inhibition in chronic refractory cardiac failure (author's transl)]. AB - Twenty patients with chronic congestive heart failure resistant to conventional treatment with digitalis, diuretics and vasodilators received captopril, an oral inhibitor of the angiotensin-converting enzyme, in daily doses of 200 mg and were followed up for 2 months or more. At 2 months, there was a significant reduction in functional symptoms (NYHA classification), bodyweight and left ventricular filling pressure, with an equally significant rise in cardiac output and sodium urinary excretion. There was no fall in systemic blood pressure, nor tachycardia. These effects were sustained in 8 patients followed up for 6 months. They seem to indicate that captopril is both effective and well tolerated in chronic congestive heart failure. PMID- 6269560 TI - Interactions between D-ala-met-enkephalin, A10 dopaminergic neurones, and spontaneous behaviour in the rat. AB - We have investigated the interaction between opioid peptides and dopaminergic A10 (DA-A10) neurones in the ventral tegmental area (VTA). The behavioural consequences of VTA infusion of d-Ala-Met-enkephalinamide (DALA) were analyzed. DALA elicited a dose-dependent increase in locomotor activity measured in photocell cages and the circular corridor. Observations in the open field and in a hole box revealed that DALA-induced behavioural stimulation was characterized by enhancement of locomotion, rearing, and number of hole visits, while grooming time and duration of hole visits were decreased. DALA-induced stimulation was reserved by naloxone, and was completely blocked by 6-OHDA destruction of DA-A10 terminals. d-Amphetamine-induced behavioural activation was potentiated by simultaneous VTA infusion of DALA which indicates that the behavioural response to DALA is dependent on DA-A10 neuronal activity. It is postulated that stimulation of opiate receptors exerts a presynaptic inhibition of an inhibitory input to DA-A10 neurones (eg. GABA or dendritic DA), thus releasing dopaminergic activity. In contrast to the acute effect, the d-amphetamine response was strongly attenuated 4 h, 1 and 6 days after VTA infusion of DALA, and returned to normal only at 14 days. This long-lasting modification may reflect decreased activity of opioid neurones, releasing the inhibition of DA-A10 neurones. Our findings suggest that endogenous opioid peptides may exert a modulatory influence on the dopaminergic mesocorticolimbic system. PMID- 6269561 TI - [Transport of H+ in mitochondria induced by the uptake of sulfite, sulfate and thiosulfate]. AB - The addition of sulphite to rat-liver mitochondria (RLM) causes an uptake of H+ that is unaffected by NEM and butylmalonate. The uptake of H+ induced by sulphate or thiosulphate is abolished by NEM and butylmalonate in freshly isolated RLM, whereas it is inhibited only by butylmalonate in sulphite-pretreated mitochondria. The data suggest that sulphite is cotransported with H+, whereas the movement of H+ associated to the uptake of sulphate or thiosulphate by RLM is mediated by either phosphate or sulphite. PMID- 6269562 TI - [Effect of insulin on cell membrane isolated from rat liver. II]. PMID- 6269563 TI - [Behavior of basal values and circadian rhythm of ACTH, cortisol, PRL and GH in a high-protein diet]. AB - Basal values and circadian rhythm of cortisol, ACTH, GH and PRL were studied in 8 normal subjects during a normal balanced caloric diet and during a high protein diet ( + 12% proteins ). GH, ACTH and cortisol levels were considerably higher following the protein rich diet probably on account of the metabolic processes directly related to the higher protein load. PMID- 6269564 TI - [Action of the unsaponifiable components of the most common edible oils on the growth of the alga Euglena gracilis. Preliminary studies]. AB - Within the sphere of the researches the biological effects of the most common edible oils (peanuts, sunflower, maize, soya and rectified olive) it has been studied the interaction between the development of the Euglena gracilis unicellular seaweed and the presence of the unsaponifiables examined in their cultures. As a biologically active substance it has been used 3,4-benzopyrene. Spectrophotometric analysis have evidenced that all the unsaponifiables, especially those of the soya seeds, caused a growth decrease of the seaweed culture. A similar effect is found in the cultures treated with aromatic hydrocarbon. PMID- 6269565 TI - [Effects of 3,4-benzopyrene on the growth and development of the sunflower (Airelle variety) in experimental culture. I) Germination of the seed and growth in height]. PMID- 6269566 TI - [Effects of 3,4-benzopyrene on the growth and development of the sunflower (Airelle variety) in experimental culture. II) Seed production]. AB - Plants of sunflower cultivated in soil enriched in 3,4 benzopyrene produces seeds which are smaller than those obtained from untreated plants. The same effect has been observed if the leaves are sprinkled with BP. The smallest seeds are produced from plants submitted to soil and leaves treatment. PMID- 6269567 TI - [Beta adrenergic receptors in the coronary vessels]. PMID- 6269568 TI - [Enhanced plasma cyclic GMP responses to methacholine in patients with Adie's syndrome (author's transl)]. PMID- 6269570 TI - Effect of the age-related immune depression induced by MTV on the in vivo growth of a mammary carcinoma. PMID- 6269571 TI - Malignant fibrous histiocytoma arising in a smallpox vaccination scar. PMID- 6269572 TI - A method to measure the water-holding properties of dietary fibre using suction pressure. AB - 1. Water-holding capacity (WHC) of dietary fibre is usually considered as the amount of water held but the manner in which water is held by the fibre matrix may be more relevant in understanding the role of fibre in nutrition. 2. A method used to determine WHC under physiological conditions has been adapted to determine how strongly water is held by fibre. Solutions of compounds, such as polyethylene glycol, of known osmotic potential are used to generate a suction pressure across a dialysis membrane containing a fibre sample. The WHC at each suction pressure can then be determined. 3. The method can be applied to water soluble and water-insoluble sources of fibre. Fibre sources studied included potato fibre concentrate, bran and gum arabic. 4. Results are comparable to other similar systems of WHC measurement for gels and suggest that vegetable fibre has water-holding properties more akin to a true gel than bran. Bran has very poor water-holding properties. 5. Differences in WHC between fibre sources are more apparent if WHC is considered as fibre concentration (g fibre/g water). 6. Differences in the water-holding properties could be important in determining fibre activity in the gut. PMID- 6269569 TI - A rapid method for the isolation of metastasizing tumour cells from internal organs with the help of isopycnic density-gradient centrifugation in Percoll. AB - Metastasizing tumour cells from a DBA/2 mouse T-cell lymphoma could be separated from the invaded tissue by isopycnic centrifugation in continuous Percoll density gradients. The metastasizing tumour cells from spleen, liver and lung, derived from a cloned lymphoma-cell line, showed a buoyant density in Percoll of 1.060 +/ 0.010. They could be separated from the host tissue, which had a higher buoyant density in the case of the spleen cells or a lower density in the case of the dead liver or lung tissue. The separated tumour cells as removed from the gradients were viable, and could be analysed by in vitro and in vivo assays. The separation procedure did not affect the expression by the tumour cells of TATAs and H-2 antigens. Furthermore, the method seemed to be applicable to the separation of human tumour cells from mononuclear cells prepared from blood samples of tumour patients by Ficoll centrifugation. PMID- 6269573 TI - High-fibre and low-fat diets in diabetes mellitus. AB - 1. Eight insulin-dependent and eight insulin-independent diabetic patients and twenty-eight non-diabetic essential hypertensive patients were given a high fibre, high-unrefined carbohydrate and low-fat diet for 3 months duration. 2. The effects of this dietary regimen on the patients' fasting blood glucose, hypoglycaemic therapy and weight was observed. 3. Fasting lipid profiles were obtained before and after 3 months on the dietary regimen, and total serum lipids and lipoprotein fractions were analysed. 4. The insulin-dependent and insulin independent diabetic patients showed a reduction in hypoglycaemic therapy, with no significant change in fasting blood glucose. The insulin-independent and non diabetic groups both showed significant weight loss. 5. The three groups of patients showed a significant reduction in cardiovascular risk factors with either an elevation of high-density lipoprotein (HDL)-cholesterol or a fall in low-density lipoprotein (LDL)-cholesterol and a reduction in the total cholesterol: HDL-cholesterol value. PMID- 6269574 TI - The effect of type and level of protein, fibre and starch on nitrogen excretion patterns in rats. AB - 1. Three series of nitrogen balance experiments were performed with growing rats to test the effect of type and level of protein, fibre and starch on N excretion patterns. The design involved eighteen treatments in a 3 X 3 X 2 factorial experiment with five rats per dietary treatment. The eighteen treatments resulted from a combination of three protein treatments, three fibre treatments and two starch treatments. Protein treatments consisted of one level (15 g N/kg DM) of casein fortified with methionine, a protein of high digestibility, and two levels (15 and 20 g N/kg DM) of autoclaved brown beans (Phaseolus vulgaris), a protein source of low digestibility. The fibre treatments were two levels of cellulose powder and one level of barley hulls. The two starch treatments were autoclaved potato starch and autoclaved and raw potato starch (1:1, w/w). 2. The inclusion of raw potato starch reduced true protein digestibility markedly when the protein source was casein, but the corresponding biological values were increased significantly with this treatment. This strongly indicated a movement of urea from the blood to the intestines. This assumption was also supported by significantly lower blood urea concentrations in animals given raw starch. The influence of raw starch on true protein digestibility was, however, significantly less when cellulose and barley hulls were included. This is probably due to reduced transit time from fibre inclusion. The nature of the gut contents also supported this hypothesis. 3. The inclusion of raw potato starch when brown beans were the source of protein had much less effect on true protein digestibility and biological value than when casein was the protein source. This was probably due to the low digestibility of DM and protein in this food leaving sufficient energy and protein for maximum microbial growth. The inclusion of fibre also had little effect on N excretion patterns with the brown-bean diets. 4. An increase in the level of brown bean inclusion reduced true protein digestibility only on the diets containing raw starch whereas the biological value was consistently reduced regardless of starch treatment. The lower biological values were associated with significantly higher blood urea concentrations. Increasing the level of brown bean inclusion also resulted in higher fresh weights of caecum, colon and contents. 5. The present work proves that, through dietary manipulation, it is possible to affect nitrogen excretion patterns in rats. PMID- 6269575 TI - The effect of dietary fibre sources on aflatoxicosis in the weanling male rat. AB - 1. Two experiments with male weanling rats were conducted in which they received individually and restrictedly either a basal semi-purified diet containing starch as the principal carbohydrate or the same diet to which mixed aflatoxins were added in quantities providing from 0.13 to 0.4 mg aflatoxin B1/kg diet. Various natural ingredients, or semi-purified sources of dietary fibre were substituted for a portion of the starch in the basal diet containing aflatoxin. The diets were fed for 13-14 weeks after which the rats were given ad lib. a commercial rodent diet until they were killed at 109 weeks of age. 2. Two further experiments were conducted in which twenty-four rats in each experiment received the basal diet plus aflatoxin, or diets in which a portion of the starch was replaced by gum arabic or by wheat offal. After 13 or more weeks the absorption, retention and excretion of 14C-labelled aflatoxin B1 was measured in each rat. 3. The addition of gum arabic or wheat bran to the diet decreased the effects of the toxin in the first two experiments, but as measured by several characteristics, only wheat bran provided an effect which persisted during the period when neither it nor the toxin was given. The effects included an apparent reduction in tumour incidence. The change in the content of starch in the basal diet, occurring as a consequence of adding the test ingredients is also considered to be an associated cause of the effects observed. 4. In comparison to starch, wheat offal increased the total 14C in the faeces and the proportion of the total found during the first 48 h after dosing. Rats receiving starch excreted more 14C in their urine and retained more 14C in their livers. The differences between gum arabic and starch were not significant as measured by 14C excretion and retention. Liver size as a proportion of carcass weight was less in rats receiving wheat offal or gum arabic, and rats receiving wheat offal had a lower incidence of fat-loaded hepatocytes. 5. The interaction of dietary toxins, or drugs, with the ingredient composition of diet may affect animal response even when the diets are adequate and similar in nutrient composition. This may be of significance both in drug safety studies and in animal production. PMID- 6269576 TI - Regeneration of ribonuclease A from the reduced protein. Isolation and identification of intermediates, and equilibrium treatment. AB - Reduced RNase A was reoxidized, and the incorrectly formed disulfide bonds were reshuffled to the native ones by oxidized and reduced glutathiones, as described in the first paper of this series. The intermediates in the regeneration of the disulfide bonds were trapped without any chemical modification and were fractionated on a carboxymethylcellulose column at pH 3.5 with a salt gradient. The elution curves of the partially regenerated RNase A from the carboxymethylcellulose column were obtained by measurement of the absorption at 275 nm and by determination of the SH content (of cysteine residues) and consisted of 11 fractions, G8, G7, G6, G5, G4, G3, G2, G1, G0, N, and F. Some of the fractions were isolated, and their measured molecular weights were consistent with those of monomeric RNase A. Fraction F had a molecular weight between that of the monomer and dimer, so that this fraction could not be identified. The regeneration pathway could be represented in terms of two simple reactions, RNase A(-SH) + GSSG in equilibrium or formed from RNase A(-SSG) + GSH and RNase A(-SH SSG) in equilibrium RNase A(greater than S2) + GSH, which produced 24 monomeric intermediates (not counting the fully reduced and the native species), which differed from each other in their amino acid composition. These 24 intermediates, plus the fully reduced protein, were assigned to fractions G8--G0 (as indicated in the last column of Table I), with the aid of data from amino acid analysis, SH content, and the elution position on the carboxymethylcellulose column chromatogram. Since the regeneration reaction rapidly reached a preequilibrium among the intermediates and the fully reduced RNase A prior to the rate-limiting steps, i.e., the relative concentrations of the intermediates and fully reduced RNase A became constant with reaction time, the populations of some of the intermediates in preequilibrium were estimated by curve fitting of the elution pattern from the carboxymethylcellulose column chromatogram. The equilibrium constants among the intermediates were calculated from their populations at preequilibrium. These equilibrium constants were "extrapolated" to other intermediates whose populations could not be estimated by curve fitting, and the relative populations of all of the possible intermediates at preequilibrium were thereby represented as a function of the concentrations of reduced and oxidized glutathiones. The regeneration process was also restarted from several of the isolated intermediates, and the resulting distribution of intermediates was consistent with that from which the equilibrium constants were determined, supporting the representation of the regeneration pathways in terms of two simple reactions. Thus, the equilibrium treatment of the regeneration pathways was useful to characterize the preequilibrium state, i.e., to identify the intermediates prior to the rate-limiting steps in the pathways and to estimate their stabilities at preequilibrium at various concentrations of reduced and oxidized glutathiones. PMID- 6269577 TI - Preparation of a fluorescent-labeled derivative of calmodulin which retains its affinity for calmodulin binding proteins. AB - Calmodulin was derivatized with 5-[[[(iodoacetyl)amino]ethyl]amino]-1 naphthalenesulfonic acid to fluorescently label the protein. This derivative (AEDANS.CaM) stimulated the Ca2+-sensitive cyclic nucleotide phosphodiesterase and formed Ca2+-dependent complexes with troponin I and the phosphodiesterase. Association between AEDANS.CaM and these proteins was directly monitored by changes in fluorescence anisotropy. The dissociation constants for the AEDANS.CaM -troponin I and AEDANS.CaM--phosphodiesterase complexes were 60 nM and 4 nM, respectively. This fluorescent derivative of calmodulin appears suitable for direct monitoring of the complexes between calmodulin and calmodulin binding proteins. Rotational diffusion of AEDANS.CaM was also measured with fluorescence anisotropy. These measurements indicated that the shape of calmodulin in solution is best approximated by a prolate ellipsoid. PMID- 6269578 TI - A putative tRNATrp gene cloned from Dictyostelium discoideum: its nucleotide sequence and association with repetitive deoxyribonucleic acid. AB - Using a total tRNA population labeled with 32P, we have cloned a number of tRNA genes from Dictyostelium discoideum. A partial sequence of a cloned 1250-base pair DNA insert, pDT-513, revealed the occurrence of a putative tRNATrp gene. In addition to the cloverleaf secondary structure, the tRNATrp gene contained all of the invariant and semiinvariant residues found in most tRNA sequences and has a 13-base-pair intron which is located one base removed from the 3' residue of the anticodon. The genomic distribution of the tRNA gene and its flanking sequences was examined via Southern annealing experiments. The structural gene is represented on at least six EcoRI fragments in the D. discoideum genome. Sequences flanking the 5' terminus of the cloned gene are repeated many times in the genome while the sequence flanking the 3' terminus of the pDT-513 DNA insert structural tRNA gene is present only once in the genome. PMID- 6269580 TI - Fluorescent and photoactivatable fluorescent derivatives of tetrodotoxin to probe the sodium channel of excitable membranes. AB - Fluorescent and photoactivatable fluorescent derivatives of tetrodotoxin (TTX) have been synthesized. N-Methylanthraniloylglycine hydrazide, anthraniloyl hydrazide, and 2-azidoanthraniloylglycine hydrazide were coupled to the carbonyl at C6 of oxidized tetrodotoxin to form stable fluorescent hydrazones. The C6 ketone can be reductively aminated with either ammonium or methylammonium acetate to form 6-amino- or 6-(methylamino)tetrodotoxin, which can then be acylated by a variety of fluorescent reagents. The biological activity, competitive binding with [3H]tetrodotoxin for the receptor on rat axonal membranes, and equilibrium binding isotherms obtained by fluorescence enhancement or anisotropy indicate that the derivatives are only about 2-5 times less active then tetrodotoxin itself. The 2-azidoanthraniloylglycine hydrazone of oxidized tetrodotoxin, when activated by light, generates a reactive nitrene which is capable of covalent insertion into the toxin receptor. The product of the photolysis is a highly fluorescent tetrodotoxin derivative which is irreversibly linked to the receptor site. The excitation and emission spectra of the fluorescent tetrodotoxin derivatives vary with solvent polarity, and this sensitivity has been used to determine the immediate environmental characteristics of the toxin binding site of the sodium channel. It is concluded that the toxin binding site is highly polar. Emission and excitation spectra reveal that radiationless energy is transferred from tryptophan residues of the receptor to the anthraniloyl group of the TTX derivatives. PMID- 6269579 TI - Characterization of purified Epstein--Barr virus induced deoxyribonucleic acid polymerase: nucleotide turnover, processiveness, and phosphonoacetic acid sensitivity. AB - The Epstein--Barr (EB) virus induced DNA polymerase has been further purified and characterized with respect to nucleotide turnover activity, processiveness of synthesis, and interaction with phosphonoacetic acid (PAA). The polymerase as purified through denatured DNA--cellulose chromatography was inseparable from a labile nuclease activity associated with an equally labile DNA-dependent nucleotide turnover function. The EB virus induced DNA polymerase even in the absence of detectable nuclease or nucleotide turnover activity was less processive in its synthesis than were lymphocyte alpha polymerase or procaryotic polymerases, and this processiveness decreased with increasing purity of the enzyme. PAA was shown to inhibit nucleotide incorporation by the EB virus induced DNA polymerase in the presence of nuclease-activated native DNA template in the manner of a pyrophosphate analogue. Under conditions in which the concentration of 3'-hydroxyl termini in the template was more limited, PAA was not inhibitory. PAA likewise failed to significantly decrease the processiveness and the nucleotide turnover function of the polymerase. PMID- 6269581 TI - Preparation and application of a photoreactive thrombin analogue: binding to human platelets. AB - alpha-Thrombin has previously been shown to bind to specific, saturable glycoproteins on the platelet surface. Modification of the thrombin active site with tosyllysyl chloromethyl ketone (TosLysCH2Cl) does not alter thrombin's binding characteristics. Interaction of alpha-thrombin with high-affinity binding sites (KD = 10(-9) M) initiates the platelet response which involves proteolytic hydrolysis of this glycoprotein. Although TosLysCH2Cl--thrombin binds to and competes for the same sites as alpha-thrombin, it cannot induce platelet stimulation because it is enzymatically inactive. In this study, we describe the preparation and application of photoreactive tritium-labeled thrombin analogues. The alpha-thrombin derivative retains its platelet-stimulating and enzymatic activities and, upon photoactivation, covalently binds to specific platelet membrane components. When freshly washed human platelets are exposed to less than saturation doses (less than or equal to 2 nM) of the thrombin derivatives in the dark and photoactivated, a single labeled complex is detected. The same experiment with greater than saturating doses (greater than or equal to 20 nM) of the thrombin derivative yields a similar complex as well as two additional ones. Molecular weight estimates of these thrombin-bound complexes were obtained by gel filtration and NaDodSO4--polyacrylamide gel electrophoresis. The low dose (high affinity) complex with TosLysCH2Cl--thrombin has an approximate molecular weight of 200 000, while that with active alpha-thrombin is smaller, approximately 120 000, due to enzymatic cleavage. The additional complexes detected with the high thrombin dose had estimated molecular weights of 400 000 and 46 000, respectively, and appeared to be the same for TosLysCH2Cl--thrombin and for the alpha-thrombin coupled platelets. These isolated complexes appear to correspond to the two previously detected populations of thrombin binding sites on the platelet. PMID- 6269583 TI - Papovavirus chromatin associated cellular endonuclease which introduces one double-strand cut in superhelical deoxyribonucleic acid. AB - Nuclear extracts from SV40-infected CV-1 monkey kidney cells and from polyoma infected 3T3 mouse cells contain an endonucleolytic activity which cleaves circular viral DNA within the chromatin to full-length linear rods [Waldeck, W., Fohring, B., Chowdhury, K., Gruss, P., & Sauer, G, (1978) Proc. Natl. Acad. Sci. U.S.A. 75, 5964-5968; Scott, W. A., & Wigmore, D. J. (1978) Cell (Cambridge, Mass.) 15, 1511-1518]. Sedimentation of the nuclear extracts through sucrose density gradients revealed a preferential binding of the endonuclease to the viral chromatin. Deproteinized exogenous covalently closed superhelical DNA substrates such as SV40 and polyoma as well as Col E1 and PM2 DNAs were linearized by the endonuclease by introduction of one double-strand break per molecule. The reaction products, FOIII unit length rods, were shown to be devoid of single-strand nicks by electrophoresis in denaturing agarose gels. The double strand break was randomly located within the various substrates since redigestion of the FOIII with single-cut restriction endonucleases failed to generate discrete pairs of reaction products. Neither linear double-stranded nor nicked circular FOII DNA structures were accepted as substrates. The endonucleolytic activity does not require the presence of ATP but is sensitive to EDTA. The enzyme activity is of cellular origin since nuclear extracts from uninfected CV-1 cells converted exogenous superhelical DNA to FOIII structures with the same properties as those described above. The biological properties of the endonuclease are discussed in the light of its possible function in permitting genetic exchange between different circular genomes. Further, it may play an essential role late during the replication of papovavirus DNA when the catenated daughter molecules are liberated from each other by an as yet unidentified mechanism. PMID- 6269582 TI - Primary sequence of two regions of mouse pro-adrenocorticotropin/endorphin. AB - The amino acid sequences of two previously uncharacterized regions of the mouse anterior pituitary common precursor to adrenocorticotropin (ACTH) and beta endorphin (pro-ACTH/endorphin) were determined. Portions of the NH2-terminal region of pro-ACTH/endorphin (called the 16K fragment) and the region between ACTH and beta-endorphin (called gamma-lipotropin) were sequenced by Edman degradations of biosynthetically labeled immunoprecipitated proteins and by Edman degradations of purified 16K fragment and beta-lipotropin. With a combination of these two approaches, 29 of the first 34 residues at the NH2-terminal end of the mouse 16K fragment were determined. The NH2-terminal region of the mouse 16K fragment was found to be nearly identical with the homologous porcine and bovine molecules. The complete amino acid sequence of the NH2-terminal region of gamma lipotropin was determined. In contrast to the highly conserved nature of the 16K fragment, mouse gamma-lipotropin was found to differ substantially from the gamma lipotropins of other species. Although the NH2-terminal and beta-melanotropin like regions of the mouse gamma-lipotropin are similar to the corresponding regions of other gamma-lipotropins, the intervening region of mouse gamma lipotropin is substantially shorter than it is in other gamma-lipotropins. In addition, mouse gamma-lipotropin lacks the pair of basic amino acids that normally mark the proteolytic cleavage site used to produce beta-melanotropin from gamma-lipotropin. PMID- 6269584 TI - Anion-dependent sodium ion conductance of platelet plasma membranes. AB - External stimulate Na+ efflux from platelet plasma membrane vesicles. Efflux is apparently electrogenic since K+ diffusion potentials induced with valinomycin (interior positive) accelerate and potentials of the opposite polarity (interior negative) inhibit. In the presence of stimulatory anions, voltage-dependent Na+ efflux is much faster than Na+-Na+ exchange in the absence of an induced membrane potential. Anions stimulate voltage-dependent efflux in the following order: SCN- greater than I- greater than NO3- greater than Br- approximately acetate approximately Cl- greater than F- approximately SO42- greater than HPO42-, gluconate, and isethionate. Thiocyanate, the most stimulatory anion, increases Na+ efflux 20-fold in the presence of a membrane potential (interior positive). Stimulation of efflux by Cl- is a saturable phenomenon with a K0.5 of 41 mM and a maximal 2-3-fold stimulation over the basal level of efflux. Neither basal nor valinomycin-stimulated efflux was influenced by the presence of the platelet aggregating agents thrombin, epinephrine, or ADP in the presence of fibrinogen. PMID- 6269585 TI - Endogenous effector of the benzodiazepine binding site: purification and characterization. AB - A protein has been isolated from the small intestine and bile duct which inhibits the binding of [3H]diazepam to specific benzodiazepine binding sites on synaptosomal membranes. When ion-exchange chromatography and gel filtration chromatography are used, this protein has been purified to apparent homogeneity. "Nepenthin" has been chosen as a name for this protein, which has an approximate molecular weight of 16 000, as determined by both sodium dodecyl sulfate polyacrylamide gel electrophoresis and gel filtration chromatography. Purified nepenthin is a competitive inhibitor of [3H]diazepam binding with a Ki = 4.6 X 10(-8) M. It does not inhibit the binding of specific ligands to the enkephalin, beta-adrenergic, gamma-aminobutyrate, or dopamine binding sites in the CNS. Neither gamma-aminobutyric acid nor glycine alters the inhibition of [3H]diazepam binding by this protein. Nepenthin can be extensively treated with proteases (trypsin, chymotrypsin, and Pronase), and inhibition of diazepam binding remains stable, indicating that a lower molecular weight fragment retains activity. Antibodies raised against this purified effector have been used in in situ double antibody labeling studies with rat brain slices. These studies indicate that cells containing an immunologically similar material are present in the deep cortical region of the forebrain. PMID- 6269586 TI - Fluorescence studies of the beta-adrenergic receptor topology. AB - The nature of the propranolol binding site of the beta-adrenergic receptor has been examined by utilizing the intrinsic fluorescence of propranolol as a probe. Additionally, the spatial relationship between the propranolol binding site and membrane tryptophan has been examined by utilizing I-quenching of intrinsic tryptophan fluorescence, chemical modification of membrane tryptophan, and singlet-singlet energy transfer between membrane-bound propranolol and tryptophan. Propranolol, at concentrations consistent with specific beta-receptor binding, protected approximately 42% of the membrane tryptophan fluorescence from I-quenching. Further, in the presence of propranolol, the apparent quenching constant (kq) was altered from 3.6 to 21.8 M-1. Reaction of the membrane fragments with 2-hydroxy-5-nitrobenzyl bromide (Koshland's reagent I) in the presence and absence of propranolol indicated that low concentrations of propranolol protected approximately 45% of the membrane tryptophan from the reagent. The singlet-singlet energy transfer from tryptophan to propranolol was determined by sensitized emission. The distance between these two species was found to be less than 20 A. These results have been interpreted to indicate that propranolol, when bound to the beta-adrenergic receptor, is situated such that its naphthyl moiety is inserted into a tryptophan-rich hydrophobic pocket of the receptor. PMID- 6269587 TI - Small unilamellar vesicles containing glycophorin A. Chemical characterization and proton nuclear magnetic resonance studies. AB - Glycophorin A, a major glycoprotein of the red blood cell, is reconstituted in small lipid vesicles (250-300 A in diameter) by using cholate detergent solubilization followed by rapid removal of cholate on a molecular sieve column. The extent of glycophorin incorporation is found to be critically dependent on the amount of cholate used, with higher amounts yielding vesicles with higher percentages of glycophorin. Vesicles with as much as 1 molecule of protein per 20 molecules of lipid can be prepared. Data on the vesicles obtained by using hydrolytic enzymes such as neuraminidase and trypsin, combined with amino acid analysis, suggest that glycophorin is incorporated in a transbilayer fashion with a high fraction of the molecules oriented with the carbohydrate-containing amino terminus to the vesicle exterior. Interaction of the protein with the hydrophobic portion of the bilayer is apparent in proton nuclear magnetic resonance spectra, and lipid line-width increases have been used to characterize the strength and stoichiometry of interaction. Glycophorin is found to affect directly as many as 40 lipid molecules per molecule of protein; however, the magnitude of the effects is not large. PMID- 6269588 TI - Phototransformation and dark reversion of phytochrome in deuterium oxide. AB - The photostationary equilibrium between the Pr and Pfr forms of phytochrome shows a strong solvent deuterium isotope effect. Phytochrome transformation from the Pr to the Pfr form exhibits a small deuterium isotope effect, in Tris-D2O upon irradiation with red light, only after a photocycling of the phytochrome. In contrast, both the photoreversion and dark reversion of Pfr show an enhanced rate in D2O. In addition to the shift in the photostationary equilibrium in D2O, another pronounced effect of D2O on phytochrome is reflected in a significant enhancement of the fluorescence quantum yield of phytochrome (Pr). This result is interpreted in terms of the primary reaction involving an intramolecular proton transfer and its consequence in the phototransformation of phytochrome. It is further proposed that a tyrosyl residue acts as a general acid catalyst in the Pr to Pfr phototransformation, which is slower in D2O than in H2O. The D2O solvent isotope effect on the photoreversion and dark reversion of Pfr is explained on the basis of acid catalysis, probably a specific acid catalysis by deuteronium ion. PMID- 6269589 TI - Time-resolved fluorescence and anisotropy decay of the tryptophan in adrenocorticotropin-(1-24). AB - The direct time-resolved fluorescence anisotropy of the single tryptophan residue in the polypeptide hormone adrenocorticotropin-(1-24) (ACTH) and the fluorescence decay kinetics of this residue (Trp-9) are reported. Two rotational correlation times are observed. One, occurring on the subnanosecond time scale, reflects the rotation of the indole ring, and the other, which extends into the nanosecond range, is dominated by the complex motions of the polypeptide chain. The fluorescence lifetimes of the single tryptophan in glucagon (Trp-25) and the 23 26 glucagon peptide were also measured. In all cases the fluorescence kinetics were satisfied by a double-exponential decay law. The fluorescence lifetimes of several tryptophan and indole derivatives and two tryptophan dipeptides were examined in order to interpret the kinetics. In close agreement with the findings of Szabo and Rayner [Szabo, A. G., & Rayner, D. M. (1980) J. Am. Chem. Soc. 102, 554-563], the tryptophan zwitterion exhibits emission wavelength dependent double exponential decay kinetics. At 320 nm tau 1 = 3.2 ns and tau 2 = 0.8 ns, with alpha 1 = 0.7 and alpha 2 = 0.3. Above 380 nm only the 3.2-ns component is observed. By contrast the neutral derivative N-acetyltryptophanamide has a single exponential decay of 3.0 ns. The multiexponential decay kinetics of the polypeptides are discussed in terms of flexibility of the polypeptide chain and neighboring side-chain interactions. PMID- 6269590 TI - Interspersion of mouse satellite deoxyribonucleic acid sequences. AB - DNA sequences with homology to the major (A + T)-rich mouse satellite component were localized in CsCl gradients by hybridization with a labeled satellite cRNA probe. Although, as expected, most of the hybridization was to DNA in the satellite-rich shoulder, substantial radioactive cRNA hybridized with DNA from denser regions of the gradient. Further examination revealed that hybridization to main-band DNA was not due to physical trapping of satellite DNA in the gradient, and melting experiments argue that the associated radioactivity was due to true RNA/DNA hybridization. Nearest-neighbor analysis of hybridized [alpha 32P]CTP-labeled l-strand cRNA indicates that hybridization to main-band DNA is by the satellite cRNA and not a contaminant. Together, these data argue that mouse satellite-like sequences are interspersed within the main-band fraction of DNA. For the support of this contention, total mouse DNA, purified main-band DNA, and purified satellite DNA were digested with EcoRI, sedimented in a sucrose gradient, and hybridized with labeled satellite cRNA. Mouse satellite DNA is not cleaved with EcoRI, so that purified EcoRI-digested satellite DNA sediments as a high molecular weight component. When total mouse DNA is digested with EcoRI, the majority of satellite-like sequences remain as high molecular weight DNA; however, significant amounts of satellite-like sequences sediment with the bulk of the lower molecular weight digested DNA, lending further credence to the argument that satellite-like sequences are interspersed with main-band DNA. PMID- 6269591 TI - Phase equilibria in binary mixtures of phosphatidylcholine and cholesterol. AB - The paramagnetic resonance spectra of two spin-labels, 2,2,6,6 tetramethylpiperadinyl-1-oxy and a head-group spin-labeled phosphatidylethanolamine (L-alpha-dipalmitoylphosphatidyl-N-ethanolamine), have been used to study solid-liquid and liquid-liquid phase separations in binary mixtures of dimyristoylphosphatidylcholine and cholesterol. A quantitative analysis of these resonance spectra supports the view that at temperatures below theta m, the chain-melting temperature of the phospholipid, and at cholesterol mole fractions Xc less than 0.2, these mixtures consist of two phases, a solid phase of essentially pure dimyristoylphosphatidylcholine and a fluid phase having a mole fraction of cholesterol equal to 0.2. The spin-label data also provide evidence for fluid-fluid immiscibility in the bilayer membrane at temperatures above the chain melting transition temperature of dimyristoylphosphatidylcholine. PMID- 6269592 TI - Thioredoxin/fructose-1,6-bisphosphatase affinity in the enzyme activation by the ferredoxin-thioredoxin system. AB - In this work we analyze the affinity relationship between photosynthetic fructose 1,6-bisphosphatase and ferredoxin and thioredoxin from spinach leaves, two components of the proposed light-activation system of this enzyme, using affinity techniques on ferredoxin- and thioredoxin-Sepharose columns. Oxidized and reduced ferredoxin did not show enzyme affinity, whereas thioredoxin, both the oxidized and the dithiothreitol-reduced form, exhibited a strong bisphosphatase affinity at pH 7.5; this thioredoxin/enzyme affinity appears diminished at pH 8.2. When the affinity experiments were performed in the presence of 5 mM Mg2+, only 30% and 12% of the bisphosphatase remained bound to the thioredoxin-Sepharose at pH 7.5 and 8.0, respectively; these percentages were reduced to 6% when the Mg2+ concentration increased to 10 mM. These results suggest that a rise of stromal pH and Mg2+ concentration can account for a loosening of the thioredoxin/bisphosphatase linkage, which could be of physiological significance in the dark-light transition. Studies on the nature of the chemical groups responsible for the affinity have shown that the thioredoxin/bisphosphatase linkage is concerned with the existence of hydrophobic clusters. We have found no difference in the behaviour of the chloroplastic thioredoxins f and m, and the cytoplasmic ones cf and cm. These results support the existence of an in vivo thioredoxin/fructose-1,6-bisphosphatase interaction, in accordance with the light activation mechanism by the ferredoxin-thioredoxin system. PMID- 6269593 TI - Formation of silver plastocyanin in Scenedesmus. AB - Silver ions up to 5 microM do not affect growth of the green microalga Scenedesmus acutus. They induce formation of protein species precipitable by an antibody specific against plastocyanin. The metal is incorporated into a part of the induced protein in competition with copper. Bismuth, lead and molybdenum had no effect. The amount of both silver- and copper-containing plastocyanins so formed apparently regulates concurrently inhibition of soluble plastidic cytochrome c-553. The silver-copper competition for the build-up of blue plastocyanin can be shown with intact cells, not with isolated algal plastocyanin. PMID- 6269594 TI - Energy status, growth and nitrogenase activity in continuous cultures of Rhizobium sp. strain CB756 supplied with NH+4 and various rates of aeration. PMID- 6269595 TI - The reaction between cytochrome c1 and cytochrome c. AB - The kinetics of electron transfer between the isolated enzymes of cytochrome c1 and cytochrome c have been investigated using the stopped-flow technique. The reaction between ferrocytochrome c1 and ferricytochrome c is fast; the second order rate constant (k1) is 3.0 . 10(7) M-1 . s-1 at low ionic strength (I = 223 mM, 10 degrees C). The value of this rate constant decreases to 1.8 . 10(5) M-1 . s-1 upon increasing the ionic strength to 1.13 M. The ionic strength dependence of the electron transfer between cytochrome c1 and cytochrome c implies the involvement of electrostatic interactions in the reaction between both cytochromes. In addition to a general influence of ionic strength, specific anion effects are found for phosphate, chloride and morpholinosulphonate. These anions appear to inhibit the reaction between cytochrome c1 and cytochrome c by binding of these anions to the cytochrome c molecule. Such a phenomenon is not observed for cacodylate. At an ionic strength of 1.02 M, the second-order rate constants for the reaction between ferrocytochrome c1 and ferricytochrome c and the reverse reaction are k1 = 2.4 . 10(5) M-1 . s-1 and k-1 = 3.3 . 10(5) M-1 . s-1, respectively (450 mM potassium phosphate, pH 7.0, 1% Tween 20, 10 degrees C). The 'equilibrium' constant calculated from the rate constants (0.73) is equal to the constant determined from equilibrium studies. Moreover, it is shown that at this ionic strength, the concentrations of intermediary complexes are very low and that the value of the equilibrium constant is independent of ionic strength. These data can be fitted into the following simple reaction scheme: cytochrome c2+1 + cytochrome c3+ in equilibrium or formed from cytochrome c3+1 + cytochrome c2+. PMID- 6269597 TI - Electron transfer between horse heart and Candida krusei cytochromes c in the free and bound states. AB - Electron transfer between horse heart and Candida krusei cytochromes c in the free and phosvitin-bound states was examined by difference spectrum and stopped flow methods. The difference spectra in the wavelength range of 540-560 nm demonstrated that electrons are exchangeable between the cytochromes c of the two species. The equilibrium constants of the electron transfer reaction for the free and phosvitin-bound forms, estimated from these difference spectra, were close to unity at 20 degrees C in 20 mM Tris-HCl buffer (pH 7.4). The electron transfer rate for free cytochrome c was (2-3).10(4) M-1.s-1 under the same conditions. The transfer rate for the bound form increased with increase in the binding ratio at ratios below half the maximum, and was almost constant at higher ratios up to the maximum. The maximum electron exchange rate was about 2.10(6) M-1.s-1, which is 60-70 times that for the free form at a given concentration of cytochrome c. The activation energy of the reaction for the bound cytochrome c was equal to that for the free form, being about 10 kcal/mol. The dependence of the exchange rate on temperature, cytochrome c concentration and solvent viscosity suggests that enhancement of the electron transfer rate between cytochromes c on binding to phosvitin is due to increase in the collision frequency between cytochromes c concentrated on the phosvitin molecule. PMID- 6269596 TI - Studies on beef heart ubiquinol-cytochrome c reductase. Quantification and distribution of the core proteins as determined by radioimmunoassay. AB - Core proteins I (Mr 50 000) and II (Mr 47 000) were isolated from beef heart ubiquinol-cytochrome c reductase, and radioimmunoassays were developed for both. Immunoreplica experiments show that antisera against each protein react with a single peptide in both isolated Complex III and in mitochondria. Thus, core proteins are not aggregated forms of smaller peptides as suggested for the yeast protein (Jeffrey, A., Power, S. and Palmer, G., Biochem. Biophys. Res. Commun. (1979) 86, 271-277). Core proteins were quantitated in Complex III and in mitochondria using radioimmunoassay. Approx. 2 mol core protein II per mol core protein I were found. A molar ratio of 1 : 2 : 2 : 1 is suggested for core protein I : core protein II : cytochrome b : cytochrome c1. Radioimmunoassay shows that the antibodies react as extensively with Complex III-bound core protein as with the isolated core proteins. In spite of this, the antibodies do not inhibit electron transport in submitochondrial particles or isolated Complex III, and they have no oligomycin- or uncoupler-like effects on submitochondrial particles oxidizing NADH. The combined results from radioimmunoassay and immunoreplica experiments strongly suggest, however, that core proteins are specifically associated with Complex III in the mitochondria, implying a specific role there. PMID- 6269598 TI - Electrocatalytic four-electron reduction of oxygen at the cytochrome c3-adsorbed electrode. AB - The electrocatalytic activity of cytochrome c3 for the reduction of molecular oxygen was characterized from the studies of the adsorption of cytochrome c3 and the co-adsorption of cytochrome cs with cytochrome c on the mercury electrode by the a.c. polarographic technique. The adsorption of cytochrome c3 on the mercury electrode is irreversible and is diffusion-controlled. The maximum amount of cytochrome c3 absorbed was 0.92 . 10(-11) mol . cm-2 at -0.90 V. The amount of cytochrome c3 in the mixed adsorbed layer with cytochrome c was determined from the differential capacitance measurement. It was shown that the fractional coverage of cytochrome c3 can be estimated from its bulk concentration and the diffusion coefficient (1.05 . 10(-6) cm2 . s-1). Cytochrome c3 catalyzes the electrochemical reduction of molecular oxygen from the two-electron pathways via hydrogen peroxide to the four-electron pathway at the mercury electrode in neutral phosphate buffer solution. The catalytic activity varies with the bulk concentration of cytochrome c3. The highest catalytic activity for the oxygen reduction (no hydrogen peroxide formation) is attained when one-half of the mercury electrode surface is covered by cytochrome c3. The addition of cytochrome c or bovine serum albumin to the cytochrome c3 solution inhibits the catalytic activity of cytochrome c3. The reversible polarographic behavior of cytochrome c3 through the mixed adsorbed layer of cytochrome c3 and cytochrome c was also investigated. PMID- 6269599 TI - Multiple sites of inhibition of mitochondrial electron transport by local anesthetics. AB - Local anesthetics and alcohols were found to inhibit mitochondrial electron transport at several points along the chain. THe anesthetics employed were the tertiary amines procaine, tetracaine, dibucaine, and chlorpromazine, and the alcohols were n-butamol, n-pentanol, n-hexanol, and benzyl alcohol. Uncoupled sonic submitochondrial particles from beef heart and rat liver were studied. We report the following: (1) All of the anesthetics were found to inhibit each of the segments of the electron transport chain assayed; these included cytochrome c oxidase, durohydroquinone oxidase, succinate oxidase, NADH oxidase, succinate dehydrogenase, succinate-cytochrome c oxidoreductase, and NADH-cytochrome c oxidoreductase. (2) NADH oxidase and NADH-cytochrome c oxidoreductase required the lowest concentration of anesthetic for inhibition, and cytochrome c oxidase required the highest concentrations. (3) We conclude that there are several points along the chain at which inhibition occurs, the most sensitive being in the region of Complex I (NADH dehydrogenase). (4) Beef heart submitochondrial particles are less sensitive to inhibition than are rat liver particles. (5) Low concentrations of several of the anesthetics gave enhancement of electron transport activity, whereas higher concentrations of the same agents caused inhibition. (6) The concentrations of anesthetics (alcohol and tertiary amine) which gave 50% inhibition of NADH oxidase were lower than the reported concentrations required for blockage of frog sciatic nerve. PMID- 6269600 TI - Copper and manganese electron spin resonance studies of cytochrome c oxidase from Paracoccus denitrificans. AB - The two-subunit cytochrome c oxidase from Paracoccus denitrificans contains two heme a groups and two copper atoms. However, when the enzyme is isolated from cells grown on a commonly employed medium, its electron paramagnetic resonance (EPR) spectrum reveals not only a Cu(II) powder pattern, but also a hyperfine pattern from tightly bound Mn(II). The pure Mn(II) spectrum is observed at -40 degrees C; the pure Cu(II) spectrum can be seen with cytochrome c oxidase from P. denitrificans cells that had been grown in a Mn(II)-depleted medium. This Cu(II) spectrum is very similar to that of cytochrome c oxidase from yeast or bovine heart. Manganese is apparently not an essential component of P. denitrificans cytochrome c oxidase since it is present in substoichometric amounts relative to copper or heme a and since the manganese-free enzyme retains essentially full activity in oxidizing ferrocytochrome c. However, the manganese is not removed by EDTA and its EPR spectrum responds to the oxidation state of the oxidase. In contrast, manganese added to the yeast oxidase or to the manganese-free P. denitrificans enzyme can be removed by EDTA and does not respond to the oxidation state of the enzyme. This suggests that the manganese normally associated with P. denitrificans cytochrome c oxidase is incorporated into one or more internal sites during the biogenesis of the enzyme. PMID- 6269601 TI - On the site of action of the inhibition of the mitochondrial respiratory chain by lipoxygenase. AB - Treatment of beef-heart submitochondrial particles with reticulocyte lipoxygenases gives rise to a strong irreversible inhibition of the NADH and succinate oxidase activities. This is not accompanied by any loss of the Fe-S clusters of the respiratory chain as determined by EPR spectroscopy. The inhibitory blockage is located between both the NADH and succinate dehydrogenases and Q-10. The inhibitory action of treatment with lipoxygenase also takes place in the absence of Q-10. The Fe-S clusters of the mitochondrial outer membrane are destroyed by lipoxygenase treatment, without any effect on the rotenone insensitive NADH: cytochrome c oxidoreductase activity. It is concluded that these clusters are not involved in this enzyme. PMID- 6269602 TI - On the mechanism of photosynthetic electron transfer in Rhodopseudomonas capsulata and Rhodopseudomonas sphaeroides. PMID- 6269603 TI - Electrogenic proton ejection coupled to electron transport through the energy conserving site 2 and K+/H+ exchange in yeast mitochondria. AB - The proton ejection coupled to electron flow from succinate and/or endogenous substrate(s) to cytochrome c using the impermeable electron acceptor ferricyanide is studied in tightly coupled mitochondria isolated from two strains of the yeast Saccharomyces cerevisiae. (1) The observed H+ ejection/2e- ratio approaches an average value of 3 when K+ (in the presence of valinomycin) is used as charge compensating cation. (2) In the presence of the proton-conducting agent carbonyl cyanide m-chlorophenylhydrazone, an H+ ejection/2e- ratio of 2 is observed. (3) The low stoichiometry of 3H+ ejected (instead of 4) per 2e- and the high rate of H+ back-decay (0.1615 ln delta (ngatom)H+/s and a half-time of 4.6 s for 10 mg protein) into the mitochondrial matrix are related to the presence of an electroneutral K+/H+ antiporter which is demonstrated by passive swelling experiments in isotonic potassium acetate medium. PMID- 6269604 TI - Chemiluminescence in the reaction of cytochrome c with hydrogen peroxide. PMID- 6269605 TI - The effect of pH and ionic strength on the pre-steady-state reaction of cytochrome c and cytochrome aa3. AB - (1) In the pH range between 5.0 and 8.0, the rate constants for the reaction of ferrocytochrome c with both the high- and low-affinity sites on the cytochrome aa3 increased by a factor of approx. 2 per pH unit. (2) The pre-steady-state reaction between ferrocytochrome c and cytochrome aa3 did nt cause a change in the pH of an unbuffered medium. Furthermore, it was found that this reaction and the steady-state reaction are equally fast in H2O and 2H2O. From these results it was concluded that no protons are directly involved in a rate-determining reaction step. (3) Arrhenius plots show that the reaction between ferrocytochrome c and cytochrome aa3 requires a higher enthalpy of activation at temperatures below 20 degrees C (15--16 kcal/mol) as compared to that at higher temperature (9 kcal/mol). We found no effect of ionic strength on the activation enthalpy of the pre-steady-state reaction, nor on that of the steady-state reaction. This suggests that ionic strength does not change the character of these reactions, but merely affects the electrostatic interaction between both cytochromes. PMID- 6269606 TI - Time-resolved resonance Raman spectroscopy of cytochrome c reduced by pulse radiolysis. AB - The first investigation of the dynamics of a redox transition of an electron transfer enzyme by time-resolved resonance Raman spectroscopy in combination with pulse-radiolytic reduction is described by an application to cytochrome c. A long lived transient state is observed upon reduction of the alkaline form of cytochrome c as a distinct frequency shift of one resonance Raman band. From the frequency in the stable oxidized state, 1567 cm(-1), this particular resonance Raman band shifts within less than 1 microsecond to 1533 cm(-1) in the transient reduced state, which has a lifetime longer than 20 ms but shorter than a few seconds. Finally, in the stable reduced state, this band is located at 1547 cm( 1). According to a previous normal coordinate analysis, this resonance Raman band can be assigned predominantly to a stretching mode of the outermost C-C bonds in the four pyrrole rings of porphyrin. This vibrational mode is influenced by the protein most directly through the covalent thioether linkages of two cysteines to porphyrin. We interpret the long lifetime of the transient state as due to the slow return of Met-80 as sixth ligand to the heme iron upon reduction of the alkaline form of cytochrome c. PMID- 6269607 TI - Regulation of phospholipid-ATPase complex interaction by the adenine nucleotide carrier. AB - (1) The effect of phospholipids on a preparation containing the ATPase complex and the adenine nucleotide carrier is studied in the presence of ligands known to affect the conformation of these components of the mitochondrial inner membrane. (2) When ATPase activity is abolished by phospholipid depletion, the reactivation induced by phosphatidylcholine is prevented by the simultaneous addition of ATP. ADP partially reproduces the ATP effect. AMP, GTP, UTP, and Pi are ineffective. (3) The influence of ATP is associated with reduced phospholipid binding to the membrane fragments and is reversible. The ATP effect on reconstitution is not manifest when phosphatidylcholine is added together with negatively charged phospholipids. (4) Carboxyatractyloside does not modify the phospholipid-ATPase complex interaction but bongkrekic acid is as effective as ATP. In the presence of ADP, the influence of bongkrekic acid is considerably increased. (5) It is concluded that the binding of ATP to the adenine nucleotide carrier enables the complex to select between the charged and uncharged phospholipids. As a result of the carrier conformational change, the ATPase complex is induced to prefer a negatively charged phospholipid environment. PMID- 6269608 TI - The triphasic reduction of cytochrome b in the succinate-cytochrome c reductase. AB - In the succinate-cytochrome c reductase, the reduction of cytochrome b has been found to be triphasic: an initial rapid partial reduction was followed first by a rapid oxidation and then finally by a slow reduction. The initial reduction of cytochrome b was faster than that of cytochrome c1 and the final slow reduction of cytochrome b began when cytochrome c1 reduction was approaching completion. In presence of the inhibitors antimycin A or HQNO the reduction of cytochrome b became monophasic. Hysteresis or a kinetic cooperative effect of a factor controlling cytochrome b oxidation has been suggested as a possible explanation for the triphasic reduction of cytochrome b. PMID- 6269609 TI - Saturation transfer ESR studies of molecular motion in phosphatidylglycerol bilayers in the gel phase: effects of pretransitions and pH titration. AB - The molecular motions of a phosphatidylglycerol spin label have been studied in dimyristoyl and dipalmitoyl phosphatidylglycerol bilayers below their ordered fluid phase transition, both in the charged state at pH 8.0 and in the protonated state at pH 1.5. The saturation transfer ESR spectra, which are sensitive to motions in the correlation time range 10(-7)--10(-3) s, show clear distinctions in the molecular motion both between the charged and the protonated states and between the states above and below the pretransition in the charged bilayers. At low temperatures, below the pH 8.0 pretransition, the saturation transfer ESR spectra indicate rather similar motion at pH 8.0 and 1.5, with the rates being approx. 2-times faster at pH 8.0. The effective rotational correlation times are approx. 0.5--1.10(-4) and approx. 1--2.10(-4) s, deduced from the outer lineheight ratios which are sensitive only to motion of the long molecular axis, and approx. 0.2--1.10(-4) and 0.2--0.5.10(-4) s, deduced from the central lineheight ratio which is sensitive also to rotation around the long molecular axis, where the first and second values refer to dimyristoyl and dipalmitoyl phosphatidylglycerol, respectively. As the temperature is increased the outer lineheight ratios at both pH values remain constant until the main transition, indicating little or no increase in motion of the long axis. In contrast, the central lineheight ratio at pH 8.0 shows a sharp decrease before the main transition, corresponding to cooperative onset of rapid rotation around the long molecular axis, at or immediately below the pretransition. The effective correlation time of this long axis rotation is approx. 10(-7) s, two orders of magnitude faster than that below the pretransition. The bilayers at pH 1.5, for which no pretransition is detected, show only a slow, non-cooperative decrease in the central lineheight ratio with increasing temperature, rapid long axis rotation in dimyristoyl phosphatidylglycerol occurring only at the main transition. The onset of long axis rotation at pH 8.0 is also detected in the conventional spectra of a steroid spin label, which begins to rotate around its long molecular axis with a correlation time of approx. 10(-9) s whilst the bilayers are still in the gel phase. These observations further strengthen the homology between phosphatidylglycerols in the charged state and the corresponding phosphatidylcholines, and provide the dynamic counterpart of the pH-induced structural change previously observed in phosphatidylglycerol bilayers in the gel phase (Watts, A., Harlos, K., Maschke, W. and Marsh, D. (1978) Biochim. Biophys. Acta 510, 63--74). PMID- 6269610 TI - Electrostatic control by lipids upon the membrane-bound (Na+ + K+)-ATPase. AB - In this paper, the membrane-bound (Na+ + K+)-ATPase from bovine brain is shown to be controlled by electrostatic alterations of the charged lipids surrounding the enzyme. The properties under investigation are the enzymatic activity, activation energy and the response of the enzymatic system to temperature. Arrhenius plots of the ATPase activity are biphasic with a break at temperature Ti. The temperature Ti, the activation energies at temperatures above and below Ti, and the enzymatic activity at any constant temperature have been shown to depend upon the concentrations of alkali and alkaline-earth metal ions in the solution. These electrolyte dependencies are ascribed to changes of electrostatic conditions at the lipids surrounding the ATPase. If the higher electrostatic screening ability of divalent ions is taken into account, the results in the presence of mono- and divalent ions become virtually the same. As a result of this work, it is concluded that electrostatic alterations are transmitted to the ATPase from the lipids of the membrane in which the enzyme is embedded. Inhibition and activation of the enzyme by mono-and divalent metal ions may thus be explained without any auxiliary hypothesis, particularly without postulating specific binding sites for the different ionic species at the protein. In addition, the specific lipid requirement of the ATPase may be understood better in the light of this interpretation. PMID- 6269611 TI - Tetrodotoxin receptors in membrane fragments: purification from Electrophorus electricus electroplax and binding properties. AB - A tetrodotoxin receptor-rich preparation of membrane fragments from the electric organ of Electrophorus electricus is described. The specific binding of neurotoxins and freeze-fracture electron microscopy are used as tools to identify and to characterize membrane fractions. Freeze-fracture electron micrographs of the electric organ demonstrate a high density of membrane particles in the extrasynaptic regions. Density gradient fractions show a broad distribution of [3H]tetrodotoxin, [3H]saxitoxin and 125I-labelled bungarotoxin binding in the range of 1.04--1.15 g/ml sucrose densities, with specific neurotoxin binding up to approx. 5 pmol/mg protein. Carrier-free column electrophoresis of density gradient fractions yields a subfraction with tetrodotoxin and alpha-neurotoxin binding up to 30 pmol/mg protein. The major part of the membrane fragments forms vesicles, which are separated by lectin chromatography into an outside-out and inside-out population. The latter represents at least 50% of the material of a density gradient fraction. For the association of tetrodotoxin, a bimolecular kinetic constant kf greater than or equal to 3.10(5) M-1.s-1 is determined. The dissociation constant is k'b = 2.5.10(-2)s-1. These data are in agreement with a thermodynamic dissociation constant of Kd = 20 nM as determined earlier for E. electricus membrane fragments by equilibrium methods (Grunhagen, H.H., Rack, M., Stampfli, R., Fasold, H. and Reiter, P. (1981) Arch. Biochem. Biophys. 206, in the press). However, these association kinetics of tetrodotoxin binding in vitro are significantly different from kinetics determined electrophysiologically in Rana (Wagner, H.H. and Ulbricht, W. (1975) Pflugers Arch. 359, 297--315) or Xenopus (Schwarz, J.R., Ulbricht, W. and Wagner, H.H. (1973) J. Physiol. 233, 167 -194). PMID- 6269612 TI - Unmasking of membrane enzyme activities and the problem of subcellular localization of adenylate cyclase in pig lymph node lymphocytes. AB - A large-scale purification of plasma membranes from pig lymph node lymphocytes is described. Centrifugation on a discontinuous sucrose density gradient was performed in a zonal rotor. Adenylate cyclase activity of untreated fractions displayed a profile different from that of plasma membrane enzymatic markers and was maximal at higher density. However, when latent adenylate cyclase was unmasked by Lubrol PX treatment, its maximum was shifted to lower density and was no longer significantly different from that of plasma membrane markers. These results are discussed in terms of cell surface topography. PMID- 6269613 TI - Location and orientation relative to the micelle surface for glucagon in mixed micelles with dodecylphosphocholine: EPR and NMR studies. AB - The spin labels, 5-doxylstearate, 12-doxylstearate, 16-doxylstearate and 1-oxyl 2,2,6,6-tetramethyl-4-dodecylphosphopiperidine, have been incorporated into dodecylphosphocholine micelles and mixed dodecylphosphocholine glucagon micelles. The EPR spectral parameters for the different spin labels and the 1H- and 13C-NMR relaxation rates for nuclei of the detergent molecules indicated that inclusion of up to one spin label molecule per micelle had little influence on the spatial organization of the micelles. Furthermore, the location and environment of the spin labels in the dodecylphosphocholine micelles were not noticeably affected by the addition of glucagon and the 1H-NMR spectra observed for glucagon in mixed spin label/deuterated dodecylphosphocholine/glucagon micelles showed that the different spin labels had essentially no effect on the conformation of glucagon. Approximate spatial locations within the micelle for the nitroxide moieties of the different spin labels were determined from the NMR relaxation rates observed for different nuclei of dodecylphosphocholine. On this basis, the line broadening of individually assigned glucagon 1H-NMR lines by the different spin labels was used to determine the approximate orientation of the polypeptide chain with respect to the micelle surface. Overall, the data indicate that the glucagon backbone runs roughly parallel to the micelle surface, with the depth of immersion adjusted so that polar and apolar side chains can be oriented towards the surface or interior of the micelle, respectively. PMID- 6269614 TI - The purification of plasma membranes from WI-38 fibroblasts: effects of ageing on their composition. AB - A three-step method for the purification of plasma membranes from WI-38 fibroblasts was developed thus allowing the recovery of 36--44% of the plasma membrane. Except in the case of galactosyltransferase, the activity of the contaminating enzymes was very low. Morphological observations confirm the presence of a homogeneous population of vesicles. Preparations obtained from young and old cell cultures were compared for their enzymatic and protein contents. With ageing the activity of 5-nucleotidase significantly increases whereas that of alkaline phosphodiesterase I decreases. Out of the 26 components detected after sodium dodecyl sulphate polyacrylamide gel electrophoresis, four decreased but only one increased. Cellular ageing seems to fulfil a specific and localized effect on the plasma membrane. PMID- 6269615 TI - Substituting manganese for magnesium alters certain reaction properties of the (Na+ + K+)-ATPase. AB - MnCl2 was partially effective as a substitute for MgCl2 in activating the K+- dependent phosphatase reaction catalyzed by a purified (Na+ + K+)-ATPase enzyme preparation from canine kidney medulla, the maximal velocity attainable being one fourth that with MgCl2. Estimates of the concentration of free Mn2+ available when the reaction was half-maximally stimulated lie in the range of the single high-affinity divalent cation site previously identified (Grisham, C.M. and Mildvan, A.S. (1974) J. Biol. Chem. 249, 3187--3197). MnCl2 competed with MgCl2 as activator of the phosphatase reaction, again consistent with action through a single site. However, with MnCl2 appreciable ouabain-inhibitable phosphatase activity occurred in the absence of added KCl, and the apparent affinities for K+ as activator of the reaction and for Na+ as inhibitor were both decreased. For the (Na+ + K+)-ATPase reaction substituting MnCl2 for MgCl2 was also partially effective, but no stimulation in the absence of added KCl, in either the absence or presence of NaCl, was detectable. Moreover, the apparent affinity for K+ was increased by the substitution, although that for Na+ was decreased as in the phosphatase reaction. Substituting MnCl2 also altered the sensitivity to inhibitors. For both reactions the inhibition by ouabain and by vanadate was increased, as was binding of [48V] -vanadate to the enzyme; furthermore, binding in the presence of MnCl2 was, unlike that with MgCl2, insensitive to KCl and NaCl. Inhibition of the phosphatase reaction by ATP was decreased with 1 mM but not 10 mM KCl. Finally, inhibition of the (Na+ + K+)-ATPase reaction by Triton X 100 was increased, but that by dimethylsulfoxide decreased after such substitution. These findings are considered in terms of Mn2+ at the divalent cation site being a better selector than Mg2+ of the E2 conformational states of the enzyme, states also selected by K+ and by dimethylsulfoxide and reactive with ouabain and vanadate; the E1 conformational states, by contrast, are those selected by Na+ and ATP, and also by Triton X-100. PMID- 6269616 TI - Slow sodium channel inactivation and the modulated receptor hypothesis: application to phenobarbital. PMID- 6269617 TI - Dog kidney (Na+,K+)-ATPase is more sensitive to inhibition by vanadate than human red cell (Na+,K+)-ATPase. AB - (Na+,K+)-ATPase (EC 3.6.1.3) from kidney is more sensitive to inhibition by vanadate than red cell (Na+,K+)-ATPase. The difference appears to be in the apparent affinities of the two enzymes for K+ and Na+ at sites where K+ promotes and Na+ opposes vanadate binding. As a result of Na+-K+ competition at these sites, reversal of vanadate inhibition was accomplished at lower Na+ concentrations in red cell than in kidney (NA+,K+)-ATPase. It is possible that vanadate could selectively regulate Na+ transport in the kidney. PMID- 6269618 TI - Use of transfection to analyze genetic information and malignant transformation. PMID- 6269619 TI - Binding of netropsin to DNA in complexes with polypeptides containing repetitive lysine sequences. AB - The interaction of the antibiotic netropsin with calf thymus DNA, T4 DNA and poly(dA-dT) . poly(dA-dT) in complexes with sequential polypeptides containing repetitive lysine sequences and histone H1 was investigated using circular dichroism spectroscopy and equilibrium dialysis. Both soluble DNA-polypeptide complexes and insoluble complexes showed binding of netropsin. The possibility of displacement of polypeptides from DNA binding sites by competition with netropsin molecules was eliminated by experiments using 14C-labelled polypeptides. From the analysis of CD titration behavior as well as from the results of equilibrium dialysis studies it follows that netropsin does not compete with polypeptides for DNA binding sites, which suggests that these two ligands occupy different sites. Various explanations for minor differences in the CD behavior of the bound netropsin in the saturation region are also discussed. PMID- 6269620 TI - Differential effect of N-carboxymethylisatoylation on the DNA polymerase activity, the 5' leads to 3'-exonuclease activity and the 3' leads to 5' exonuclease activity of DNA polymerase I of Escherichia coli. AB - Treatment with native DNA polymerase I of Escherichia coli with the acylating agent N-carboxymethylisatoic acid anhydride (NCMIA) results under specific conditions in a rapid loss of polymerase activity, an increase in 5' leads to 3' exonuclease activity and in unchanged 3' leads to 5'-exonuclease activity. When a nucleoside triphosphate and Mg2+ was present the polymerase activity was completely protected against the effect of NCMIA. Treatment with higher concentration of the acylating agent under these conditions led to a loss of 3' leads to 5'-exonuclease activity without any appreciable loss of polymerase activity. Treatment with NCMIA of the two catalytically active fragments of the enzyme led to very similar results. In this case both the polymerase activity and the 3' leads to 5'-exonuclease activity deteriorated more rapidly on treatment with the acylating reagent. The increase in 5' leads to 3'-exonuclease activity as a result of modification of the native enzyme appeared to be due to a change in the optimum conditions with regard to concentration of the assay buffer used. These changes are very similar to those seen when the polymerase is cleaved by limited proteolysis. From the results obtained it is concluded that NCMIA reacts primarily with a site at or near the triphosphate-Mg2+ complex binding site, leading to an almost complete loss of polymerase activity. The acylating reagent reacts also with another group on the native enzyme resulting in a modification of the 5' leads to 3'-exonuclease activity, and at high concentrations with a group leading to a slow loss of 3' leads to 5'-exonuclease activity. PMID- 6269621 TI - A basic isozyme of yeast glyceraldehyde-3-phosphate dehydrogenase with nucleic acid helix-destabilizing activity. AB - A nucleic acid helix-destabilizing protein has been purified from Saccharomyces cerevisiae using affinity chromatographic techniques. Crude protein extracts at low ionic strength (approx. 0.05 M) were applied sequentially to tandem columns of native DNA-cellulose, aminophenyl-phosphoryl-UMP-agarose, poly(I . C)-agarose, poly(U)-cellulose and denatured DNA-cellulose. The 2 M NaCl eluant of the poly(U) cellulose column was dialyzed to low ionic strength and recycled through native DNA-cellulose, poly(I . C)-agarose and poly(U)-cellulose. Purified helix destabilizing protein eluted from the poly(U)-cellulose between 0.1 and 0.5 M NaCl. On the basis of enzymatic activity, immunological cross-reactivity, mobility on SDS gels, amino acid analysis and preliminary peptide mapping experiments, this material was identified as an isozymic fraction of glyceraldehyde-3-phosphate dehydrogenase. The major crystallizable isozyme of this enzyme from yeast is, however, considerably more acidic than the helix destabilizing protein, and displays significantly lower helix-destabilizing activity. Stoichiometric levels of the isolated protein at low (approx. 0.01) ionic strength depress the Tm of poly(A-U) and poly [d(A-T)] by as much as 28 and 22 degrees C, respectively. Longer double helices, poly(A . U) and Clostridium perfringens DNA are also denatured by the helix-destabilizing protein, but at relatively slow rates. The binding of this protein to [3H]-poly(U) on nitrocellulose filters in [Na+]-dependent, with a 50% reduction at 0.09 M NaCl. Based on its effect on the circular dichroism spectrum of poly(A), the protein was shown to distort the conformation of the polynucleotide chain. An analogous protein from mammalian cells, P8, was also shown to depress poly(A-U) Tm. PMID- 6269622 TI - Phosphorylation of high mobility group protein HMG 14 by a cyclic GMP-dependent protein kinase from avian liver nucleoli. AB - A cyclic GMP-dependent protein kinase was previously found in the 0.3 M NaCl extract of avian liver nucleoli [1]. The kinase phosphorylates preferentially a protein of a molecular weight of approximately 11,000 present in calf thymus histone mixture (type IIA, Sigma) and in isolated liver nucleoli. Further studies with purified protein substrates have now indicated that the chromatin-associated protein, which is preferentially phosphorylated by the cyclic GMP-dependent kinase, is high mobility group protein HMG 14. Histone H1 was also a relatively good phosphate acceptor but in this case the phosphorylation was not cyclic GMP dependent and therefore due to a different protein kinase present in the partially purified nucleolar extract. Acid hydrolysis of the phosphorylated HMG 14 and subsequent analysis by chromatography and high-voltage electrophoresis indicated that the phosphorylated amino acid residue in HMG 14 is phosphoserine. PMID- 6269623 TI - Purification of the sequence-specific endonuclease SinI from Salmonella infantis. PMID- 6269624 TI - Differential reactivities at restriction enzyme sites. AB - A method has been developed to measure the rates of digestion by restriction enzymes at individual sites. This involves a simple arithmetical treatment of the integrated areas from a densitometer scan of an ethidium bromide stained gel. We have used this method to study the digestion by HpaI, HincII and SalI of pBR322 and phi X174 DNA, and the effect of various DNA binding ligands. One of the two HpaI sites in phi X174 DNA is much more sensitive to inhibition by ligands such as netropsin, which display a preference for AT base pairs, than is the other site. Inspection of the sequences flanking the restriction sites shows that the former contains a much higher proportion of AT base-pairs than dose the latter. The opposite phenomenon is observed with the two HincII sites in pBR322. This illustrates the importance of neighbouring sequences in the interaction between restriction enzymes and their cleavage sites in DNA. PMID- 6269625 TI - Type I DNA topoisomerases from mammalian cell nuclei interlock strains and promote renaturation of denatured closed circular PM2 DNA. AB - Type I DNA topoisomerases from mouse ascites cell nuclei and from rat liver cell nuclei act on denatured viral closed circular PM2 DNA to produce molecules with a highly contracted structure as well as fully duplex non-supercoiled covalently closed circular molecules. Highly contracted DNA molecules contain a novel type of topological linkage in which a strand in one region of the double-stranded molecule passes between the strands in another region of the circular molecule one or more times. Since it is also found that the action of the topoisomerase promotes renaturation of complementary strands in denatured closed circular DNA, it is suggested that formation of contracted DNA structures proceeds through renatured, duplex intermediates with highly negative superhelix densities that contain small single-stranded regions. PMID- 6269626 TI - Restriction endonuclease analysis of mitochondrial DNA from virus-transformed, tumor and control cells of human, hamster and avian origin. Sequence conservation and intraspecific variation. AB - This study compares over 70 recognition sites for restriction endonucleases on mtDNAs from various control versus malignant cells, derived from Syrian hamster, chick embryo, viper and human cells, exhibiting a wide spectrum of cellular transformation and tumor histories. Agents for transformation in vitro and in vivo include Rous sarcoma viruses, simian virus 40, polyoma virus and adenovirus. The results show a striking intraspecific sequence homogeneity of different mtDNAs regardless of tissue origin and oncogenic history. mtDNA from human biopsy specimens of tumor versus pathologically normal areas yielded indistinguishable restriction cleavage patterns reflecting either the "wild-type' form (with seven restriction endonucleases) or, in one individual, a variant pattern detected with HpaI. The precise position of the HpaI variant site was determined on the physical map of human mtDNA. Additional cleavage sites in the previously reported restriction map of Syrian hamster mtDNA are also presented. It is concluded that (1) mtDNA sequence in higher animal cells are highly conserved in malignant transformation; (2) no evidence for integration of viral sequences in mtDNA is apparent; (3) variant patterns in mtDNA are likely to be intraspecific polymorphisms that pre-exist neoplastic transformation. The possibility is discussed that altered regulatory interaction with the mitochondrial genome, rather than evident changes in mtDNA primary structure, determine anomalous mitochondrial functions in malignant transformation. PMID- 6269628 TI - Preparation and specificity of antibodies directed toward the ribose methylated nucleotide, 2'-O-methylguanosine 5'-monophosphate. AB - Antibodies have been produced that recognize the ribosome methylated nucleotide, 2'-O-methylguanosine 5'-monophosphate, pGm. Specificity was tested in a radioimmunoassay. Other ribose methylated nucleotides, deoxyguanosine, and guanosine 5'-monophosphate exhibited negligible cross-reactivity. Elements of antibody recognition, in descending order of importance, were the parent base, the methylated ribose moiety, and the phosphate group. PMID- 6269627 TI - Heterogeneity of neutral ribonuclease II and ribonuclease II-inhibitor complex from mouse skeletal muscle. AB - Using either DEAE-cellulose chromatography or pH 4--6 isoelectric focusing, we have separated mouse skeletal muscle neutral RNAase II-inhibitor complex into two fractions (designated alph and beta). para-Hydroxymercuriphenyl-sulfonate-induced dissociation/inactivation of the inhibitor yields free RNAase II enzyme fractions with differing pH profiles, CM-cellulose chromatographic behavior and reactivity with the RNAase II inhibitor of human placenta. However, the free RNAase fractions react equally with purified inhibitor from skeletal muscle and are not separable by pH 8--9.5 isoelectric focusing. These data suggest that mouse skeletal muscle has two heterogeneous forms of RNAase II. Additionally, heterologous RNAase II inhibitors may be used as investigational tools when probing neutral RNAase II heterogeneity. PMID- 6269629 TI - The region of transcriptional initiation in Lytechinus variegatus rRNA genes. AB - A sea urchin ribosomal DNA 1.9 kilobase BamHI fragment adjacent to the 5' end of the 18 S gene has been mapped with the restriction enzymes, XhoI, EcoRi, SmaI and HinfI. A 270 basepair fragment which most likely contains the 5' end of the presumed primary transcript of rRNA was identified by hybridization of [32P]DNA fragments to total nuclear RNA separated on methylmercury hydroxide gels and bound to diazobenzyloxymethyl paper. Under these denaturing conditions the size of Lytechinus variegatus precursor rRNA was determined to be 7.2 kilobases (33 S). PMID- 6269630 TI - Pisum sativum endonuclease. Studies on substrate specificity and possible use as a biochemical tool. AB - An endonuclease purified from germinating pea (Pisum sativum) seeds has been shown to catalyze the hydrolysis of heat-denatured single-stranded DNA. Since P. sativum endonuclease shows appreciable activity in the presence of DNA destabilizing agents and, unlike many similar endonucleases, significant activity at neutral pH, it is a potentially valuable tool for studies of the secondary structure of nucleic acids. The residual hydrolysis of duplex DNA is directed towards partially denatured, A,T-rich areas in native DNA. The rate of hydrolysis of deoxypolynucleotides was in the order poly(dT) greater than denatured DNA greater than poly(dA) greater than poly(dA-dT) = native DNA. Neither poly(dC), poly(dG) nor poly(dC).poly(dG) were attacked by the enzyme. Supercoiled, covalently closed circular phage PM2 form I DNA is converted to singly hit nicked circular form II and doubly hit linear from III duplexes. Prolonged treatment with enzyme does not further cleave the linear form III DNA. Addition of increasing concentrations of NaCl in the incubation mixture suppresses the conversion of form I to form II, but not the conversion of form II to form III, which is enhanced with the increasing ionic strength. The enzymatically relaxed circular form, I degree, obtained by unwinding of supercoiled DNA with a DNA relaxing protein, is resistant to the action of the enzyme. Molecules with intermediate superhelix densities do not serve as substrates. The sites of cleavage of P. sativum endonuclease in PM2 DNA occur within regions that are readily denaturable in a topologically constrained superhelical molecule. PMID- 6269631 TI - Terminal strand-switching of E. coli RNA polymerase transcribing a truncated DNA fragment. AB - When transcribing a restriction fragment containing the promoters and the first part of the rrnE operon of Escherichia coli, RNA polymerase holoenzyme starts exclusively on the promoters. Besides run-off transcripts, molecules longer than template-size are formed by terminal strand switch. PMID- 6269632 TI - Characterization of the cloned Escherichia coli dihydrofolate reductase. AB - Dihydrofolate reductase (5,6,7,8-tetrahydrofolate: NADP+ oxidoreductase, EC 1.5.1.3) was purified from Escherichia coli strains that carried derivatives of the multicopy recombinant plasmid, pJFM8. The results of enzyme kinetic and two dimensional gel electrophoresis experiments showed that the cloned enzyme is indistinguishable from the chromosomal enzyme. Therefore it can be concluded that these strains are ideal for use as a source of enzyme for further studies on the biochemistry and regulation of this important enzyme. The plasmid derivatives were constructed by recloning experiments that utilized several restriction endonucleases. From the analysis both of these plasmids and the purified dihydrofolate reductase enzymes it was possible to deduce the location and orientation of the dihydrofolate reductase structural gene on the parent plasmid, pJFM8. PMID- 6269633 TI - An aberrant adenylate kinase isoenzyme from the serum of patients with Duchenne muscular dystrophy. AB - The sera from patients with human Duchenne (X-linked) progressive muscular dystrophy contain elevated adenylate kinase (ATP: AMP phosphotransferase, EC 2.7.4.3) activities, in addition to their characteristically high creatine kinase (ATP; creatine N-phosphotransferase, EC 2.7.3.2) activities. By agarose gel electrophoresis of human Duchenne dystrophic serum, the presence of an apparently normal human serum adenylate kinase together with a variant species of adenylate kinase was detected. The latter enzyme species appeared, in its mobility, to be similar to that of the normal human liver-type adenylate kinase. The presence of this aberrant liver-type adenylate kinase could also be demonstrated by characteristic (for the liver type) inhibition patterns with P1,P5-di-(adenosine 5')pentaphosphate, 5,5'-dithiobis(2-nitrobenzoate) and phosphoenolpyruvate. On the other hand, by inhibition titrations with an anti-muscle-type adenylate kinase, hemolysates from the erythrocytes of several Duchenne and Becker's dystrophics were found to contain approx. 96% muscle-type adenylate kinase and their serum approx. 97% muscle-type adenylate kinase. These same patients contained approx. 89% M-M type creatine kinase in their serum (by inhibition against anti-human muscle-type creatine kinase) indicative of the presence also of M-B plus B-B type active isoenzymes. All of these data can best be explained by the presence of a variant or mutant adenylate kinase isoenzyme in the dystrophic serum. This isoenzyme appears to resemble the liver type in its inhibition patterns with P1,P5-di(adenosine-5')pentaphosphate, 5,5'-dithiobis(2 nitrobenzoate) and phosphoenolpyruvate, and in its heat stability (compare also the agarose gel electrophoresis pattern); but structurally, it is a muscle type, or derived from a muscle type, as shown immunologically by inhibition reactions with anti-muscle-type adenylate kinase. Whether this is a fetal-type isoenzyme of adenylate kinase will require further investigation. PMID- 6269634 TI - Characterization of activatable form of prolyl hydroxylase in L929 fibroblasts. AB - Prolyl hydroxylase (prolyl-glycyl-peptide, 2-oxoglutarate : oxygen oxidoreductase, EC 1.14.11.2) activity in a sonicated preparation of early log phase L929 cells could be increased 3-4-times by preincubation of the sonicate with all cofactors of proline hydroxylation, such as ascorbate, Fe2+ and alpha ketoglutarate. An "activatable" form of the enzyme is produced in these cells due to a deficiency of one of the cofactors in these cultures. The activatable form is found to be different from the active enzyme with respect to its stability to heat and dithiothreitol denaturation. The activatable form has different ionic properties and could be separated from the active enzyme by DEAE-Sephadex chromatography. The available evidence suggests that the activatable form is a tight complex produced by the enzyme with underhydroxylated collagen, the latter being produced by a cofactor deficiency in the cells. Activation of this complex follows the hydroxylation of the substrate and its subsequent release from the bound enzyme. PMID- 6269635 TI - Reverse and forward reactions of carbamyl phosphokinase from Streptococcus faecalis R. Participation of nucleotides and reaction mechanisms. AB - The participation of Mg complex of nucleoside diphosphates and nucleoside triphosphates in the reverse and forward reactions catalyzed by purified carbamyl phosphokinase (ATP : carbamate phosphotransferase, EC 2.7.2.2) of Streptococcus faecalis R, ATCC-8043 were studied. The results of initial velocity studies of approx. 1 mM free Mg2+ concentration have indicated that in the reverse reaction MgdADP was as effective a substrate as MgADP. The phosphoryl group transfer from carbamyl phosphate to MgGDP, MgCDP and MgUDP was also observed at relatively higher concentrations of the enzyme and respective magnesium nucleoside diphosphate. In the forward direction MgdATP was found to be as efficient a phosphate donor as MgATP. On the other hand, Mg complexes of GTP, CTP and UTP were ineffective even at higher concentrations of the enzyme and respective magnesium nucleoside triphosphate. Product inhibition studies carried out at non inhibitory level of approx. 1 mM free Mg2+ concentration have revealed that the enzyme has two distinct sites, one for nucleoside diphosphate or nucleoside triphosphate and the other for carbamyl phosphate or carbamate, and its reaction with the substrates is of the random type. Further tests of numerical values for kinetic constants have indicated that they are partially consistent with the Haldane relationship which is characteristic of rapid equilibrium and random mechanism. PMID- 6269636 TI - Inhibition properties of Sepharose-bound trypsin and a protease on the surface of Ehrlich ascites tumour cells. AB - Ehrlich ascites cells have been shown to possess a protease with beta naphthylamidase activity located on the surface of these cells. This enzyme is protected from the inhibitory action of protein inhibitors of trypsin (EC 3.4.21.4) in free solution, but is inhibited by high concentrations of active site-directed inhibitors of trypsin. We believe the protection against inhibition is provided by the location of this protease on the cell surface. We employed a model system of trypsin coupled to Sepharose to demonstrate the protective action of an inert surface, resulting in a marked reduction in inhibition of trypsin Sepharose, compared to trypsin in free solution, when exposed to both high and low molecular weight inhibitors. This cell protease has been shown to play a role in activation of the zymogen of collagenase exported by tumour cells. This role may have important implications for tumour cell invasion of the intercellular matrix. PMID- 6269638 TI - A novel enzyme, tagatose kinase, from Mycobacterium butyricum. AB - A novel enzyme catalyzing the phosphorylation of D-tagatose to D-tagatose 6 phosphate with ATP has been identified in extracts of dulcitol-grown Mycobacterium butyricum. The enzyme was purified 100-fold with 29% recovery. It required Mg2+, Mn2+ or Fe2+ and showed maximum activity at pH 7.5. The molecular weight as determined by Sephadex G-100 filtration amounted to 63 000. The apparent Michaelis constants for D-tagatose and ATP were 0.8 and 1.0 mM, respectively. The enzyme preparations were not very sensitive to SH group inhibitors and heavy metals but rapidly lost activity on heating above 50 degrees C. PMID- 6269637 TI - Kinetic properties of a nucleoside phosphotransferase of chick embryo. AB - 1. A nonspecific nucleoside phosphotransferase (nucleotide : 3'-deoxynucleotide 5'-phosphotransferase, EC 2.7.1.77), purified from chick embryos, catalyzes the transfer of phosphate ester from a nucleotide donor to a nucleoside acceptor. 2. The enzyme exhibits sigmoidal kinetics with respect to nucleoside monophosphate donors, but with respect to nucleoside di- or triphosphate donors and nucleoside acceptors hyperbolic kinetics were obtained. 3. The nucleoside phosphotransferase of chick embryo is unstable to heat and is protected from inactivation by a large number of nucleosides. 4. Nucleoside di- and triphosphates lower both the concentration of nucleoside monophosphates required for half-maximal velocity and the kinetic order of reaction measured with these phosphate donors. On the contrary, nucleoside di- or triphosphate do not modify the kinetic parameters evaluated for nucleoside acceptors. 5. We suggest that the nucleoside phosphotransferase contains both substrate and regulatory sites. It seems that the free apoenzyme is converted, by means of cooperative interactions between regulatory sites, into an enzyme-nucleotide complex, which is particularly stable at 37 degrees C. PMID- 6269640 TI - Saturable high affinity binding, uptake and degradation of rat plasma lipoproteins by isolated parenchymal and non-parenchymal cells from rat liver. PMID- 6269639 TI - Evidence for a regulatory role of CTP : choline phosphate cytidylyltransferase in the synthesis of phosphatidylcholine in fetal lung following premature birth. AB - The sequence of reactions which function to incorporate choline into phosphatidylcholine was investigated in lung from fetuses following premature delivery. The rate of [methyl-14C]choline incorporation by rat lung slices into phosphatidylcholine increases following premature delivery at both 20 and 21 days gestation. The increase in choline incorporation is primarily due to an increased specific activity of phosphorylcholine resulting from a decreased pool size of phosphorylcholine. The decrease in the concentration of phosphorylcholine following premature delivery is apparently caused by an increased activity of cytidylyltransferase which leads to an increase in the conversion of phosphorylcholine to phosphatidylcholine. The total activity of choline kinase, cytidylyltransferase, cholinephosphotransferase and phosphatidate phosphohydrolase did not change significantly. However, the cytidylyltransferase activity in the microsome fraction increased following premature delivery at 20 and 21 days gestation. The amount of cytidylyltransferase in the H form in the cytosol fraction increased following premature delivery at 21 days gestation but not at 20 days gestation. The results are interpreted to indicate that the active form of cytidylyltransferase in lung cells is the membrane-bound enzyme and this form increases following birth resulting in an increased synthesis of phosphatidylcholine. PMID- 6269642 TI - Pulmonary phosphatidic acid phosphohydrolase. Developmental patterns in rat lung. PMID- 6269641 TI - Activation of CTP : phosphocholine cytidylyltransferase in rat lung by fatty acids. AB - CTP : phosphocholine cytidylyltransferase activity exists in both the microsome and cytosol fractions of adult lung, 36 and 59%, respectively. Although these enzyme activities are stimulated in vitro by added lipid activators (i.e. phosphatidylglycerol), there are significant levels of activity in the absence of added lipid. We have removed endogenous lipid material from microsome and cytosol preparations of rat lung by rapid extraction with isopropyl ether. The extraction procedure did not cause any loss of cytidylyltransferase activity in the cytosol. After the extraction the enzyme was almost completely dependent upon added lipid activator. Isopropyl ether extraction of microsome preparations produced a loss of 40% of the cytidylyltransferase activity, when measured in the presence of added phosphatidylglycerol. Lipid material extracted into isopropyl ether restored the cytidylyltransferase activity in cytosol. The predominant species of enzyme activator in the isopropyl ether extracts was fatty acid. A variety of naturally occurring unsaturated fatty acids stimulated the cytidylyltransferase to the same extent as phosphatidylglycerol. Saturated fatty acids were inactive. PMID- 6269643 TI - Pulmonary phosphatidic acid phosphohydrolase. Developmental patterns in rabbit lung. AB - 1. The developmental patterns of the phosphatidic acid phosphohydrolase activities in developing rabbit lung were determined using both aqueously dispersed phosphatidic acid (PAaq) and membrane-bound phosphatidic acid (PAmb) as the substrates. 2. The specific activities and the total activities of the PAmb dependent phosphohydrolase activities in the microsomes and to a lesser extent in the homogenates increased between 26 and 30 days gestation (term 31), but decreased in the adult. The PAaq-dependent activities demonstrated a smaller increase during late gestation and a decrease in the adult. 3. There was little change in either the Paaq- or the Pamb-dependent activities in the cytosol between 25 and 30 days gestation. The total activities per g lung were increased in the adult. 4. Fractionation of adult cytosol on Bio-Gel A5m revealed PAaq dependent activities in the void volume (Vo) (50% total), a peak with an apparent molecular mass (Mr) = 150 kdaltons (25% total) and a peak with Mr = 110 kdaltons (25% total). The PAaq-dependent peak with Mr = 150 kdaltons was not detected in the fetal cytosols. 5. Gel filtration revealed PAmb-dependent activity in the Vo (15% total), a major peak with an apparent Mr = 390 kdaltons (44% total) and minor peaks with Mr = 240 kdaltons (16% total) and Mr = 110 kdaltons (24% total). Little change was observed during development. 6. Thermal denaturation studies on he PAmb-dependent activities in the cytosols produced biphasic curves with a rapidly inactivated component and a relatively heat-stable component. The thermal denaturation profiles for the PAmb-dependent activities remained relatively unaltered throughout fetal development. The thermal denaturation profiles of the PAaq-dependent activities in the fetal cytosols were also biphasic. In contrast, the inactivation profiles of the PAaq-dependent activities in adult cytosol were monophasic. PMID- 6269644 TI - Studies of diacylglycerol cholinephosphotransferase and diacylglycerol ethanolaminephosphotransferase activities in Tetrahymena microsomes. AB - Microsomes isolated from Tetrahymena pyriformis synthesized phosphatidylcholine and phosphatidylethanolamine by CDPcholine: 1,2-diacylglycerol cholinephosphotransferase (EC 2.7.8.2) and CDPethanolamine: 1,2-diacylglycerol ethanolaminephosphotransferase (EC 2.7.8.1), utilizing ethanol-dispersed dioleoglycerol. Cholinephosphotransferase and ethanolaminephosphotransferase activities have similar dependences on MgCl2 and MnCl2, but the latter was more effective than the former for both enzyme activities. The V values for 1,2 dioleoylglycerol obtained at optimal conditions were 1.8 nmol/min per mg microsomal protein for cholinephosphotransferase and 0.6 nmol/min per mg microsomal protein for ethanolaminephosphotransferase. Both enzymes could not utilize 1,3-dioleoylglycerol or 1-oleoylglycerol as substrates. Cholinephosphotransferase had an apparent Km for CDPcholine of 11.7 microM with 1,2-dioleoylglycerol and was inhibited by CDPethanolamine competitively. On the other hand, ethanolaminephosphotransferase has an apparent Km for CDPethanolamine of 8 microM and CDPcholine was a noncompetitive inhibitor of ethanolaminephosphotransferase activity. Furthermore, despite the marked alteration of phospholipid composition occurring during the temperature acclimation of Tetrahymena cells, both enzyme activities showed similar dependences on growth and incubation temperatures. This may imply that the final step of de novo synthesis of two major phospholipids does not participate in the thermally induced modification of the profile of phospholipid polar head group in membranes. PMID- 6269645 TI - Does the neurotropic action of adrenocorticotrophic hormone involve a lipolytic step? AB - The stimulatory effect of adrenocorticotrophic hormone (ACTH)-related synthetic peptides on the hydrolysis of emulsified trioleoylglycerol by a rat brain lipase was studied. The ACTH effect was related to the net positive charge associated with the basic amino acid residues at position 15-18 in the ACTH sequence, as well as to the presence of the NH2-terminal amino acid residues at position 1-2. The ACTH effect on lipolysis was markedly reduced when lipids were partially removed from the enzyme preparation by extraction with chloroform/acetone. Full restoration of the stimulatory effect was obtained upon addition of phosphatidylcholine (2 mg/ml) to the lipolytic medium. Striking similarities between the structure-activity pattern for the stimulatory effect of ACTH on brain lipase and that described for the receptor-mediated actions of ACTH on adrenal and fat cells suggest that the ACTH effect might involve recognition of a binding site associated with the brain enzyme. Complete log concentration response curves obtained with four ACTH analogs may also be regarded as simulating hormone-receptor interaction. These findings are discussed in relation to the possibility that ACTH may have a neurohormonal role via lipase-catalyzed changes in the lipid matrix of membranes. PMID- 6269647 TI - Functional and conformational properties of mouse hemoglobins. AB - Hemoglobins from four strains of mice (C3H/SW, DBA/2J, C57BL6/Kh and A.TH) examined showed pH-dependent heme-heme interactions. The oxygen affinity and cooperativity are reduced at acidic pH. The oxygen equilibrium parameters increase as a function of increasing pH and at physiological pH values they are similar to the corresponding values of human hemoglobin A. The nitrosyl derivatives of these mouse hemoglobins undergo a quaternary structural transition to the T state in going from pH 7.0 to 6.0. These functional and conformational properties are indicative of destabilised oxy structures of mouse hemoglobins at acidic pH. This study also confirms that the cysteine residue at beta 13(A10) position has no influence on the oxygen equilibrium properties or conformation of the molecule. PMID- 6269646 TI - Modulation of phosphatidylcholine synthesis in vitro. Inhibition of diacylglycerol cholinephosphotransferase and lysophosphatidylcholine acyltransferase by centrophenoxine and neophenoxine. AB - 1,2-Diacyl-sn-glycerol : CDPcholine cholinephosphotransferase (EC 2.7.8.2) and acyl-CoA : 1-acyl-sn-glycero-3-phosphocholine acyltransferase (EC 2.3.1.23) activities of rat liver microsomes can be inhibited by centrophenoxine (N,N dimethylaminoethyl p-chlorophenoxyacetate). This inhibition is brought about by the intact centrophenoxine molecule rather than by the products of hydrolysis. A nonhydrolyzable ether analog of centrophenoxine was synthesized (neophenoxine; N,N-dimethylaminoethyl p-chlorophenoxyethyl ether) and proved most effective in inhibiting the two routes of phosphatidylcholine biosynthesis. While 50% inhibition of the cholinephosphotransferase was attained at 5 mM neophenoxine, 50% inhibition of the acyltransferase required 0.6 mM neophenoxine levels only. Inhibition of the cholinephosphotransferase (Ki approximately 1.5 mM) and the acyltransferase (Ki approximately 1 mM) by neophenoxine was shown to be noncompetitive. Other membrane-bound enzymes, such as glucose-6-phosphatase, monoacylglycerol lipase, alkaline phosphatase or phospholipase A2 were not affected by the inhibitors. Because of this specificity, and because of the high affinity of the microsomal membrane for such agents, centrophenoxine and neophenoxine should prove useful for controlling phosphatidylcholine synthesis and for modulating the phosphatidylcholine deacylation-reacylation cycle. PMID- 6269649 TI - Immunological and chemical characterization of rat liver cytochrome c oxidase. AB - Rat liver cytochrome c oxidase (ferrocytochrome c: oxygen oxidoreductase; EC 1.9.3.1) was separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis into 12 different polypeptide chains. Specific antisera against the holoenzyme and against purified subunits IV and VIII were used to characterize the enzyme complex. The antiserum against subunit IV precipitates from sodium dodecyl sulfate-dissociated mitochondria only subunit IV and from Triton X-100-dissolved mitochondria all 12 polypeptide chains, indicating their integral location within the enzyme complex. Different antisera against the holoenzyme only precipitate subunits IV, V and VIb from sodium dodecyl sulfate dissociated mitochondria, suggesting the location of these subunits on the surface layer of the complex. Subunit VIII is thought to be located within the complex, since a specific antiserum does not precipitate the complex. The amino acid composition of all 12 protein subunits is different, thus excluding their origin from proteolytic degradation. The proteolytic degradation of subunit IV into IV during isolation of the enzyme was corroborated by the very similar amino acid composition of both proteins. PMID- 6269648 TI - Characterization of a macromolecular aggregate of ovine pituitary corticotropin beta-lipotropin common precursor. AB - A macromolecular aggregate of corticotropin-beta-lipotropin common precursor had been observed in ovine pituitary preparations as an excluded fraction of Sephadex G-200 gel filtration. This fraction could not penetrate a 10% gel during sodium dodecyl sulfate-polyacrylamide gel electrophoresis, when 2-mercaptoethanol or other disulfide-cleaving agents were not present in the buffer used to solubilize the protein preparation prior to the electrophoresis. On a 4.6% gel (acrylamide:bisacrylamide, 20:1), the material migrated as a diffuse band to a position between those of beta-galactosidase (Mr 130 000) and myosin (Mr 200 000). Both observations were consistent with an apparent Mr greatly in excess of that of the corticotropin-beta-lipotropin common precursor reported by many investigators. Neither 5% SDS nor 1% Triton X-100 could dissociate the macromolecular aggregate, but 2-mercaptoethanol and urea, either alone or in combination, were able to dissociate it to two main protein components, one of which was identified as corticotropin-beta-lipotropin with an apparent Mr of 34 000. The fact that urea alone could dissociate this macromolecular aggregate led us to believe that it might be a non-covalent aggregate and that 2 mercaptoethanol probably did not achieve the dissociation through the cleavage of an interchain disulfide bond but by bringing about conformational changes as a result of reduction of intrachain disulfide bonds so that aggregation became unfavorable. Moreover, the dissociation by urea or by 2-mercaptoethanol was found to be irreversible. The origin of the macromolecular aggregate of corticotropin beta-lipotropin common precursor remains obscure. PMID- 6269650 TI - The effect of nutritional status and of glucocorticoid treatment on the protein kinase isozyme pattern of liver parenchymal cells. AB - In this study, we have employed native polyacrylamide gels to resolve protein kinase isozymes in cytosol samples from rat liver parenchymal cells. Five distinct bands of protein kinase activity were detected. Four of these were found to be cyclic AMP-dependent. Cytosols of isolated hepatocytes from fed and fasted rats were compared using the gel system. The resulting protein kinase activity profile revealed no marked differences in isozyme pattern or kinase activity between the two nutritional states. Isolated hepatocytes from fed rats were placed in primary culture and after 24 and 48 h cytosol samples were prepared and assayed for protein kinase activity using the gel system. The isozyme pattern remained intact for cells maintained in either Waymouth's or Swim's-77 medium for at least 48 h after inoculation into culture, and the isozyme pattern was not altered by glucocorticoid treatment. PMID- 6269652 TI - The actions of various cytochalasins on mouse adrenal tumor cells in relation to trophic stimulation of steroidogenesis. PMID- 6269651 TI - Increased beta-adrenergic receptor complement in androgen-induced mouse kidney hypertrophy. AB - Treatment of female mice with testosterone propionate led to a pronounced, but gradual increase in kidney beta-adrenergic receptor complement. The specific binding of [125I]iodohydroxybenzylpindolol rose 2-3-fold above the control levels after 8-12 days of the treatment. No significant changes were detected prior to the fourth day of androgen administration. No gross changes in either the binding strength or cooperativity of the binding were apparent in membrane preparations from treated animals. Averages of the high-affinity binding constant estimates were 1.3 +/- 0.3 nmol in controls, vs. 1.6 +/- 0.5 nmol in treated animals (15 groups each) in competition with pindolol, with the Hill slope factors of 0.98 +/ 0.08 for controls, and 0.91 +/- 0.07 for the treated animal membrane preparations. Scatchard estimates of the binding constants in self-competed [125I]iodohydroxybenzylpindolol binding were about 160 pmol in both control and treated animals. Competition experiments using isoproterenol also indicated similar dissociation constants (151 +/- 16 nmol) for control and treated groups. Na+/K+-activated ATPase (EC 3.6.1.3) was also found to be increased at the 12th day of the androgen treatment (to 74% above control levels). PMID- 6269653 TI - The effect of metabolites, papaverine, and probenecid on cyclic AMP efflux from isolated rat Islets of Langerhans. PMID- 6269654 TI - [Inhibition of chloride permeability and sodium transport in frog skin by mercusal and ethacrynic acid]. AB - Potential difference across the frog skin is increased 1-2 min after addition of 0.063-1.0 mg/ml ethacrynic acid or 0.2-1.0 mg/ml mercusal to outside Ringer solution. Within this time the short-circuit current remains unchanged or increased. Potential difference and short-circuit current are diminished after the addition of ethacrynic acid or mercusal to inside solution. This effect is similar to that of ouabain. These findings suggest that ethacrynic acid and mercusal inhibit chloride channel in the apical cell membrane, and inhibit sodium transport in the basolateral membrane. PMID- 6269655 TI - [Mechanism for incorporating iron into living tissue]. PMID- 6269656 TI - [Aggregation of rhodopsin molecules during damaging exposure of photoreceptor membranes to light]. AB - Injuring light induced structural changes in rod outer segment (ROS) membranes are studied using "ST EST spectroscopy" for spin labelled rhodopsin, ESR of lipid spin label and SDS gel-electrophoresis. Free SH-group content of rhodopsin and lipid peroxidation level were simultaneously determined as well. A decrease of rotational mobility of rhodopsin in ROS induced by prolonged illumination is shown to result from irreversible protein aggregation caused by disulfide bond formation between "hydrophobic" SH-groups of rhodopsin. Some decrease of lipid microviscosity and degree of order are found, in contrast to considerable rise in microviscosity due to Fe2+-ascorbate induced lipid peroxidation of ROS membranes. Lipid oxidation is found to accelerate protein aggregation which in its turn influences the state of lipid bilayer. PMID- 6269658 TI - 3',5' Cyclic nucleotide phosphodiesterase from human platelets: effect of heat upon the multiple forms and their interconversion. AB - A 33,000 g supernatant from human platelets showed a biphasic heat inactivation curve at 45, 50 and 55 degrees C of the cAMP and cGMP phosphodiesterase. This could suggest the presence of two differently heat sensitive phosphodiesterases. However, a preparation heated for 30 min at 55 degrees C, where only the apparently thermostable form of the enzyme remained, still displayed the same characteristics as the starting material, i.e. two apparent Km values for cAMP, a cAMP specific activity lower at low protein concentration (less than 50 micrograms/ml) than at high protein concentration(greater than 100 micrograms/ml), and three peaks of activity upon linear sucrose density gradient. Moreover, a biphasic inactivation curve was again observed after a second heat treatment. These results demonstrated that the heat effect is not a simple protein denaturation of one of two independent species. A study at different temperatures of the profile of the cAMP phosphodiesterase upon sucrose gradient demonstrated that the dissociated form was predominant at high temperature whereas lower temperature favored the associated form. During heat treatment, the dissociated form is at first denatured and this leads to a shift in the equilibrium between the associated and dissociated forms of the phosphodiesterase in favor of the dissociated form. From the overall results, one can draw a model for phosphodiesterase regulation by dissociation-reassociation. PMID- 6269657 TI - [Channel-forming protein from a Na, K-ATPase preparation from porcine renal medulla]. AB - Protein inducing formation of the monovalent cation selective channels on bilayer lipid membrane (BLM) was isolated by ethanol extraction from the great subunits of Na+, K+ ATPase or pork kidney microsomes. Conductance of the single channels in the presence of 2 microgram/ml of protein, 0.016 A KC1 and 0.08 M NaCl is equal to 40 p. The membrane potential of a ten-fold potassium ion gradient is close to a theoretical one. Ouabain (5 X 10(-5) M-1 X 10(4) M) inhibits the formation of the channels. KCl (0.03-0.08 M) eliminates the ouabain effect. PMID- 6269660 TI - [Phenylalanyl-tRNA synthetase from E. coli MRE-600. Effect of chemical modification of lysine residues on the enzyme interaction with substrates]. AB - The effect of modification of Phe-RSase from E. coli MRE-600 by pyridoxal-5' phosphate and 2', 3'-dialdehyde derivative of ATP and L-phenylalanynyl-5' adenylate obtained by periodate oxidation on the enzyme interaction with substrates was investigated. It was shown that modification of Phe-RSase by pyridoxal-5'-phosphate and 2', 3'-dialdehyde derivative of ATP leads to a decrease of the aminoacylation rate without changing the rate of the ATP-[32P] pyrophosphate exchange reaction. The substrate analogs L-phenylalanynol and L phenyl-alanynyladenylate increase the degree of Phe-RSase inactivation in the aminoacylation reaction. tRNAphe strongly protects the enzyme against inactivation. ATP, both in the absence (in case of modification with pyridoxal-5' phosphate) and in- the presence of Mg2+ and phenylalanine (in case of modification with o-ATP) exhibits a pronounced protective effect. L-Phe does not protect the enzyme against the inactivation by pyridoxal-5'-phosphate or o-ATP. The dissociation constant of the Phe-RSase[14C]-Phe-tRNAphe complex increases 2.5 -- 5-fold after the enzyme modification by pyridoxal-5'-phosphate, while the Km value for tRNAphe decreases approximately two times in the aminoacylation reaction. There are no changes in the Km values for amino acid and ATP and the Hill coefficients for all substrates tested. Modification of Phe-RSase by pyridoxal-5'-phosphate leads to a decrease of stability of the aminoacyladenylate -- enzyme complex. Oxidized L-phenylalanynyladenylate does not produce enzyme inactivation either by aminoacylation or in the isotropic ATP-PP iota exchange reaction. It is assumed that Phe-RSase from E. coli MRE-600 contains some lysine residues essential for binding and aminoacylation of tRNA, which do not occur in the ATP-binding subsite and aminoacyladenylate formation center. PMID- 6269659 TI - [Comparison of physico-chemical properties of two forms of dopamine-beta hydroxylase from chromaffin granules]. AB - The purification procedures of both soluble and membrane-bound forms of dopamine beta-hydroxylase have been developed. The membrane-bound form was solubilized by a detergent. Both preparations have been obtained in electrophoretically homogeneous form. The yield of soluble and membrane-bound enzyme forms by a described procedure was 22 mg and 15 mg, correspondingly, from 100 g of chromaffin granules paste. A comparative analysis of the main physico-chemical properties of the two enzyme forms has shown their identity. The effects of pH, ionic strength, oxidants and reducers on the EPR spectra of the two forms of dopamine-beta-hydroxylase have been investigated. A comparison of the EPR spectra of the two forms of the enzyme suggests that the copper environment of soluble and membrane-bound dopamine-beta-hydroxylases is practically identical. PMID- 6269661 TI - Cyclic 3',5'-adenosine monophosphate in umbilical cord blood of the newborn infant: relation to fetal stress and plasma catecholamines. AB - Cyclic 3',5'-adenosine monophosphate (cyclic AMP) was analyzed in the venous blood of the mothers and in the umbilical vein and artery of the infant at birth. In general, higher cyclic AMP levels were found in the umbilical vein than in the artery which were similar to the maternal values. Asphyxia and vacuum extraction were associated with significantly higher cyclic AMP levels, while the concentration was lower after elective cesarean sections than after uncomplicated vertex deliveries. The cyclic AMP concentrations were inversely correlated to pH and directly related to the catecholamine concentrations. The origin and possible significance of cyclic AMP in umbilical cord plasma is discussed. PMID- 6269662 TI - Amygdaloid kindling and cerebrospinal cyclic nucleotides. AB - The kindling model of experimental epilepsy is characterized by a persistent seizure pattern and long-lasting seizure susceptibility without associated tissue damage. In order to examine the relationship between CSF cyclic nucleotides and epilepsy. CSF cAMP and cGMP were measured before and after kindling, or after electrically induced seizures. Cyclic AMP and cGMP levels in cisternal CSF decreased significantly 1 week after the amygdaloid kindling. This finding suggests decreased levels of brain cAMP and cGMP in this type of epileptogenesis. A slight increase in CSF cyclic nucleotides concentrations was found after triggering both partial and generalized seizures. There was, however, no difference in increase of cAMP and cGMP levels between partial seizure and generalized convulsion, indicating that differences in intensity ictal or postictal events cannot be reflected in the CSF cyclic nucleotide concentrations. PMID- 6269663 TI - Ovarian gonadotropin receptors during experimental ovarian cyst formation in the rat. PMID- 6269664 TI - Development of the porcine fetal adrenal in late gestation. PMID- 6269665 TI - On mechanisms of head-to-head association in bovine spermatozoa. PMID- 6269666 TI - Slower step of the polycyclic aromatic hydrocarbons metabolism: kinetic data from microspectrofluorometric techniques. AB - A microspectrofluorometer has been used for kinetic studies of the decrease of benzo(a)pyrene and benzo(k)fluoranthene fluorescence. This decrease is observed for single living cells: L cells and human peripheral blood monocytes, after their incubation which culture medium containing these compounds and washing the petri dish with fresh medium. The entire fluorescence spectra is recorded at given time intervals in order to watch at some eventual spectral modification. The fluorescence decrease is monoexponential and its parameters are computed with a program based on the least squares fit method. Such determination shows no difference between the calculated rate constants of metabolisation for B(a)P and B(k)F and, as long as we consider L cells with a similar morphological shape, only statistical fluctuations of the rate constants of metabolism are observed. As compared, monocytes show faster kinetics of the decrease of the B(a)P intracellular fluorescence due to B(a)P metabolism, and also a more reached dispersion of the values of the rate constant than the one observed for L cells indicating some heterogeneity in the monocyte population of each donor. PMID- 6269668 TI - Effects of pressure and temperature on the reactions of horseradish peroxidase with hydrogen cyanide and hydrogen peroxide. AB - Reactions of ferric horseradish peroxidase with hydrogen cyanide and hydrogen peroxide were studied as a function of pressure. Activation volumes are small and differ in sign (delta V = 1.7 +/- 0.5 ml/mol for peroxidase + HCN and -1.5 +/- 0.5 ml/mol for peroxidase + H2O2). The temperature dependence of cyanide binding to horseradish peroxidase was also determined. A comparison is made of relevant parameters for cyanide binding and compound I formation. PMID- 6269667 TI - The sting. Melittin forms channels in lipid bilayers. AB - Melittin, a toxin of bee venom, is a cationic polypeptide composed of 26 amino acids. The six residues of the C-terminal end are polar and 19 of the 20 residues of the N-terminal end are hydrophobic. Exposure of the lecithin bilayer to melittin results in the formation of channels that are more permeable to anions that to cations. Unilateral addition of melittin produces a voltage-dependent increase in membrane conductance when the side where the polypeptide is present in made positive but not when it is made negative. At a fixed voltage, the conductance increases with the fourth power of the melittin concentration in the aqueous phase. At a fixed peptide concentration, the conductance increases approximately e-fold per 6-mV increase in the electrical potential difference across the membrane. These results suggest that four melittin monomers are needed to form a channel and, furthermore, that a minimum of four equivalent electronic charges need to be displaced by the electrical field to explain the voltage dependence of the conductance. PMID- 6269669 TI - Analysis of the potentiometric titration of reduced horse heart cytochrome c. PMID- 6269670 TI - Analysis of the ionization constants and heats of ionization of reduced and oxidized horse heart cytochrome c. PMID- 6269671 TI - The mass spectra of the trimethylsilyl derivatives of cis- and trans- hexahydrocannabinol and their hydroxy and acid analogues. AB - The mechanisms leading to the major ions in the mass spectra of the trimethylsilyl derivatives of cis- and trans-hexahydrocannabinol, five monohydroxy analogues, eight dihydroxy analogues, and two carboxylic acid derivatives were investigated with the aid of deuterium labelling and high resolution mass measurements. PMID- 6269672 TI - Membrane phosphorylation: a crucial role in the action of insulin, EGF, and pp60src? PMID- 6269673 TI - Stimulation of Escherichia coli adenylate cyclase by lactose in strains carrying mutations in lactose permease. AB - When a wild-type strain of Escherichia coli contains lactose permease, the accumulation of cyclic AMP (cAMP) by intact cells is inhibited by lactose. This inhibitory effect of lactose is observed in a strain with a mutant cAMP phosphodiesterase and therefore involves a regulation of adenylate cyclase activity. Some E. coli strains carrying mutations in lactose permease show an effect opposite to that of the wild-type strain; the accumulation of cAMP by intact cells is stimulated by lactose, but only when the mutant permease is present. Insertion of lactose permease into the membrane of cells can produce a change in the specific activity of adenylate cyclase; induction of the wild-type transporter is correlated with a decrease in the specific activity, while implantation of a mutant form of lactose permease can lead to an increase in the specific activity. From these data, it is suggested that the state of the lactose transporter in the cell membrane influences the activity of adenylate cyclase. PMID- 6269674 TI - Ventilatory and circulatory effects of doxapram, mediated by carotid body chemoreceptors. PMID- 6269675 TI - Stimulant effect of almitrine (S 2620) on the rabbit carotid chemoreceptor afferent activity. PMID- 6269676 TI - [Injectors of inert and radioactive gas boluses (author's transl)]. PMID- 6269677 TI - Varicella-zoster virus in the human corneal endothelium: a case report. PMID- 6269678 TI - Inactivation of herpes simplex virus by a pregnene derivative (TX 3047). AB - 1. Two strains of independently purified Herpes simplex virus type 1 were irreversibly inactivated after incubation with the pregnene derivative methyl-p toluene sulphonate of diethylamino-3-beta-ethoxy-20-hydroxy-pregn-5-ene (TX 3047) in vitro. 2. RNA and DNA synthesis (both cellular and viral) were studied in the presence of TX 3047. Viral and cellular DNA synthesis but not viral RNA synthesis was reduced. 3. Formation of infectious particles was not affected by TX 3047 if the parental virus was absorbed to the cell before it was incubated with TX 3047. This suggests that TX 3047 acts at the level of the membrane. PMID- 6269679 TI - Captopril and the maintenance of blood pressure after sinoaortic denervation in the rabbit. AB - 1. At a dose of 1 mg/kg intravenously, captopril lowered blood pressure in conscious rabbits, that had undergone denervation of sinoaortic baroreceptors, but had no effect on heart rate. In sham-operated controls, this dose caused only an increase in heart rate. 2. In the same experiments, captopril caused a substantial inhibition of plasma angiotensin converting enzyme (CE) activity of rapid onset and gradual decline over 2 to 3 h. The time course of recovery of blood pressure and plasma CE activity were similar. 3. Saralasin, by intravenous infusion, lowered blood pressure in sinoaortic rabbits but to a smaller extent than captopril. 4. The fall in blood pressure observed after captopril is not dependent on the integrity of baroreceptor afferents. PMID- 6269680 TI - Sedative activity of cannabis in relation to its delta'-trans tetrahydrocannabinol and cannabidiol content. AB - 1. The oral sedative potencies of cannabis herb, crude ethanolic and petroleum ether fractions, were assayed against delta'-trans-tetrahydrocannabinol (THC) administered orally to mice, by measuring spontaneous motor activity over 30 min periods, at selected times, up to 6 h. 2. The THC contents of the extracts were determined chemically by gas-liquid chromatography analysis and the B/C ratio (biological activity divided by chemical activity) calculated for each. The B/C values for cannabis herb, which contained THC but no CBD, was 4.47 and for ethanolic and petroleum-ether extracts, 5.26 and 4.39, respectively. 3. The sedative potency expressed as SDA50, the dose required to give 50% effect over 6 h, was 1.06 (0.98 to 1.15) mg/kg for THC; 4.72 (4.22 to 5.27) mg/kg for cannabidiol and 1.26 (1.22 to 1.80) mg/kg for chlorpromazine. 4. An infusion of cannabis herb made with boiling water was shown to have sedative activity of very low potency. 5. When the cannabinoids were completely extracted from a sample of herb with petroleum-ether the aqueous and ethanolic extracts of the marc had some sedative activity; but the 70% ethanolic fraction had none. 6. The sedative activity of THC, cannabis herb and a water soluble fraction is blocked by aspirin, a cyclo-oxygenase inhibitor, and restored by prostaglandin E2 (PGE2). 7. The sedative effect of chlorpromazine is not blocked by aspirin. PMID- 6269682 TI - Binding of [3H]-prazosin and [3H]-dihydroergocryptine to rat cardiac alpha adrenoceptors. AB - 1 [3H]-prazosin binds specifically to a single class of alpha-adrenoceptors in rat cardiac membranes (KD25 degrees C = 0.2 nM). 2 That these receptors are of the alpha 1-type was indicated by competition studies, i.e. alpha 1-antagonists such as prazosin and (2-(2,6-dimethoxyphenoxyethyl) aminomethyl-1, 4-benzodioxane (WB 4101) were more potent than the alpha 2-antagonists, yohimbine and piperoxan in inhibiting [3H]-prazosin binding. 3 A comparative study of [3H]-prazosin binding and [3H]-dihydroergocryptine binding to cardiac membranes showed that both [3H]-prazosin and [3H]-dihydroergocryptine (at low concentrations) bind to alpha 2-adrenoceptors, while [3H]-dihydroergocryptine (at higher concentrations) also binds to another class of sites. PMID- 6269681 TI - Tolerance of guinea-pig airway muscle preparations to relaxant agonists induced by chronic exposure to isoprenaline in vivo. AB - 1 The histamine sensitivities of complete tracheal spiral preparations from guinea-pigs were similar to those of paired half tracheal tissues. 2 Airway muscle preparations from animals chronically treated with isoprenaline showed a significant increase in resting tone and a significant decreased responsiveness to histamine. 3 The paired half tracheal preparations exhibited no significant difference when either their isoprenaline or theophylline sensitivities were compared. 4 Paired half tracheal muscle preparations from chronically treated animals (0.4 mumol, 4.0 mumol, and 40.0 mumol isoprenaline, 3 times daily for 21 days, s.c.) showed a significantly reduced sensitivity to isoprenaline when compared to appropriate controls. 5 Theophylline concentration-effect curves for the paired half tracheal preparations from chronically treated guinea-pigs (4.0 mumol and 40.0 mumol isoprenaline) were significantly reduced compared with appropriate controls. 5 Indomethacin treatment reversed the isoprenaline desensitization induced by chronic treatment (0.4 mumol isoprenaline) but was ineffective in animals that received the higher doses of isoprenaline in vivo. PMID- 6269683 TI - Comparison of the effects of methoxamine with those of noradrenaline and phenylephrine on single cerebral cortical neurones. AB - 1 The technique of microelectrophoresis was used to compare the actions of methoxamine, noradrenaline and phenylephrine on single neurones in the somatosensory cerebral cortex of the rat.2 Methoxamine evoked only excitatory responses on cortical neurones. The methoxamine-sensitive cells were also excited by phenylephrine; cells excited by methoxamine could either be excited or depressed by noradrenaline.3 Methoxamine appeared to be less potent than either noradrenaline or phenylephrine in evoking excitatory responses.4 Responses to methoxamine had a slower time course than responses to either noradrenaline or phenylephrine, both the latencies to onset and the recovery times being longer for responses to methoxamine than for responses to noradrenaline or phenylephrine.5 When the absolute mobilities of methoxamine, noradrenaline and phenylephrine were compared using an in vitro method, no significant differences were found between the mobilities of the three ionic species, suggesting that the three drugs have similar transport numbers. Thus the differences in potency between methoxamine and the other two drugs, and the difference between the time courses of responses to methoxamine and the other two drugs, are presumably of biological origin.6 The alpha-adrenoceptor antagonist, phenoxybenzamine, antagonized equally excitatory responses to methoxamine and noradrenaline, and responses to methoxamine and phenylephrine, without affecting responses to acetylcholine.7 When responses to methoxamine and noradrenaline and responses to methoxamine and acetylcholine were summated on the same cells, the net responses were smaller than those expected on the basis of additive effects; the deviation from additivity was greater in the case of the summation of responses to methoxamine and noradrenaline than in the case of summation of responses to methoxamine and acetylcholine. This observation is consistent with the hypothesis that the interaction between methoxamine and noradrenaline follows the model of competitive dualism, whereas the interaction between methoxamine and acetylcholine follows the model of functional synergism.8 The results suggest that methoxamine may act as a partial agonist at excitatory alpha-adrenoceptors on cerebral cortical neurones. PMID- 6269684 TI - A control study of dietary factors in renal stone formation. AB - Fifty-one first admission renal stone patients and an equal number of controls were interviewed and a dietary history of the average weekly intake was collected from each participant. A comparison of the dietary intake per kilogram body weight in each group was made using standard statistical procedures. None of the nutrient intakes showed a significant difference, but dietary fibre intake and the percentage of energy provided by carbohydrate were consistently higher in the control group, whereas the percentage of energy provided by fat was consistently higher in the renal stone group. PMID- 6269686 TI - Gastric mucus secretion in ranitidine-treated patients. PMID- 6269685 TI - Cimetidine-induced erythema annulare centrifugum: no cross-sensitivity with ranitidine. PMID- 6269687 TI - Outbreak of rotavirus gastroenteritis among premature infants. PMID- 6269689 TI - Denervation supersensitivity for benzodiazepine receptors in the rat substantia nigra. AB - The injection of kainic acid into the substantia nigra causes, 3 weeks after treatment, a 40% decrease in the total number of binding sites for [3H]diazepam with an increase in the dissociation constant. This decrease was restored to approximately normal by the subsequent injection of kainic acid into the striatum, homolateral to the lesioned substantia nigra. The injection of kainic acid into the striatum of intact animals failed to modify the number of [3H]diazepam binding sites but increased the KD. The results indicate that benzodiazepine binding sites in the substantia nigra are partly located on kainic acid sensitive elements (probably interneurons) and, partly, on kainic acid resistant ones. These binding sites become supersensitive after degeneration of striato-nigral pathways. The possible role of GABAergic denervation of the substantia nigra in the development of benzodiazepine binding sites supersensitivity is discussed. PMID- 6269690 TI - Increased choline kinase activity in the rat superior cervical ganglion after axonal injury. AB - The activity of choline kinase (CK) was examined in the rat superior cervical ganglion (SCG) during development and following postganglionic axotomy. The highest specific enzyme activity (nmol phosphorylcholine/mg protein/h) 52 +/- 8, is observed 5 d before birth, then it rapidly decreases by about 50%, reaching at the day of birth levels observed in the ganglion throughout life. During development the total enzyme activity per ganglion is increased steadily until it reaches a 5-fold increase which parallels the increase in protein content. Following axotomy the enzyme activity per ganglion is rapidly increased by about 2-fold between 1 and 5 d postoperative and then gradually decreases reaching control levels at 30 d. The transient increase in enzyme activity parallels the increase in protein content of the axotomized ganglia. The peak increase in enzyme activity coincides with the peak chromatolytic response of the axotomized ganglion. We conclude that choline kinase activity is transiently increased within neurons after axonal injury, and that this event represents an effort of the nerve cell body to enhance its phosphatidylcholine biosynthesis essential for new membrane synthesis during the regeneration of the cut axon. PMID- 6269688 TI - Chlorpropamide alcohol flush and circulating met-enkephalin: a positive link. AB - Chlorpropamide-alcohol flushing may be due to sensitivity to endogenous opiates. To investigate this possibility the plasma met-enkephalin and beta-endorphin responses to sherry with and without chlorpropamide were studied in six patients with non-insulin dependent diabetes and in six normal subjects. After chlorpropamide all patients showed a rise in met-enkephalin concentrations from a basal level of 50 +/- 7.2 ng/l to a peak of 75 +/- 8.1 ng/l (p less than 0.001). In contrast, before chlorpropamide treatment was started met-enkephalin values did not change after alcohol. No significant changes in beta-endorphin values were observed. In six normal subjects pretreated with chlorpropamide the met enkephalin concentration also rose from a basal level of 72 +/- 15 ng/l to a peak of 103 +/- 9.4 ng/l (p less than 0.002). Again, the met-enkephalin rise was not observed after placebo. Neither beta-endorphin concentrations nor facial temperature changed significantly. These data suggest that endogenous opiates may be implicated in CPAF. Furthermore, this is the first study in which a significant change in circulating met-enkephalin values has occurred. PMID- 6269691 TI - A comparison of the actions of pentobarbitone and etomidate on [3H]GABA binding to crude synaptosomal rat brain membranes. PMID- 6269692 TI - Effects of centrally administered endogenous opioid peptides on drinking behavior, increased plasma vasopressin concentration and pressor response to hypertonic sodium chloride. AB - Intracerebroventricular (i.v.t.) administration of beta-endorphin or leucine5 enkephalin inhibited drinking behavior, the pressor response and increased plasma vasopressin concentration stimulated by an acute elevation in CSF sodium chloride concentration (10 microliter, 1 M NaCl i.v.t.). These effects of endogenous opioid peptides were prevented by naloxone, indicating opiate receptors were required for the biologic response. Drinking behavior associated with regulatory stimuli operant during dehydration was also inhibited by opioid peptides. beta Endorphin (i.v.t.) delayed the onset and/or reduced the volume of water consumed in response to hypertonic sodium chloride (relative cellular dehydration), polyethylene glycol (hypovolemia) and food-associated drinking behavior. Inhibition of drinking did not appear related to sensory-motor dysfunction as another motivated behavior, eating (onset, amount consumed) was unaffected by beta-endorphin. It is concluded from these results that centrally administered endogenous opioid peptides inhibit sodium chloride-stimulated cerebral mechanisms affecting blood pressure and hydration. PMID- 6269693 TI - Clonidine releases immunoreactive beta-endorphin from rat para distalis. AB - Clonidine (10(-6), 10(-7) M) evokes the release of beta endorphin-like immunoreactivity (beta-END-LI) from cell cultures of anterior (pars distalis) but not neurointermediate (pars nervosa plus pars intermedia) lobe of the rat pituitary. This drug-induced secretion is blocked by alpha-adrenergic (phenoxybenzamine, yohimbine; 10(-5) M) but not beta-adrenergic (propranolol, 10( 5) M) antagonism. Gel filtration (Sephadex G-50) reveals that beta-END-LI released from anterior lobe cells consists of 2 major forms of immunoreactivity which coelute with beta-lipotropin or beta-endorphin standards. Conversely, beta END-LI released spontaneously from neurointermediate lobe cells almost entirely corresponds to beta-endorphin. The data show that alpha-adrenergic stimulation by clonidine releases beta-END-LI selectively from cells of anterior but not neurointermediate lobe in vitro and suggests that the clonidine-induced release of pituitary beta-END-LI we have observed in vivo occurs in part by direct action on the corticotrophs of the pars distalis. PMID- 6269694 TI - Opiate receptor heterogeneity in human brain regions. PMID- 6269695 TI - High affinity GABA receptors-autoradiographic localization. AB - The distribution of the high affinity gamma-aminobutyric acid (GABA) receptor labeled by [3H]muscimol, has been studied in the rat brain by light microscopic autoradiography. Receptors in slide-mounted tissue sections were labeled in vitro with [3H]muscimol. Most of the gray matter areas presented grain densities significantly higher than background or white matter areas. Wide variations in receptor densities were found between different brain areas and nuclei. Areas with very high grain densities are the granule cell layer of the cerebellum, external plexiform layer of the olfactory bulb and nuclei of the thalamus, such as the ventral nucleus, lateral nucleus and dorsal geniculate body. The molecular layer of the hippocampus and the external (I-IV) layers of the cortex are also rich in GABA receptors. The basal ganglia have moderate concentrations of receptors, while the pons, medulla and brainstem have only low concentrations of autoradiographic grains. These distributions are discussed in correlation with the known distribution of GABAergic terminals and the presence of inhibitory GABAergic mechanisms. PMID- 6269696 TI - Human brain protein phosphorylation in vitro: cyclic AMP stimulation of electrophoretically-separated substrates. AB - In vitro phosphorylation of electrophoretically-separated brain proteins was studied in human frontal cortex obtained 3-16 h post-mortem from 13 patients ages 3 days-82 years with extensive, mild or no neuropathological involvement. In 12 of the 13 cases, cyclic AMP increased incorporation of phosphate into acid precipitable protein. Analysis of the autoradiographic profiles of separate proteins indicated that phosphorylation of the doublet of molecular weight 86 80,000 was stimulated by cyclic AMP in certain samples. This doublet corresponded to the cyclic AMP stimulated doublet from rat frontal cortex we have termed band D-1,2 (proteins Ia and Ib of Ueda and Greengard). Of special interest was the fact that, while co-migration was observed in the other phosphoprotein bands studied, band D-1,2 of humans consistently migrated slightly less than rat protein band D-1,2. This difference was not a function of post-mortem time, subcellular fraction or buffer used in the reaction phosphorylation assay. The use of post-mortem tissue was not a contributing factor as the retardation in band D-1,2 migration was still observed when post-mortem rat brain was used for comparison. In two human post-mortem samples, there was no measureable band D-1,2 phosphorylation even in the presence of cyclic AMP. This was the case in both homogenate and crude synaptosome/mitochondrial preparations. Band F-1 (mol. wt. = 47,000) was not observed in any of the human samples studied. This is consistent with prior studies in rat which show that band F-1 phosphorylation is not detected in post-mortem brain, Band F-2 (mol. wt. 41,000) recently identified as pyruvate dehydrogenase, was lightly phosphorylated under the reaction conditions used in this study. PMID- 6269697 TI - Rapid effect of enucleation on neurotransmitter receptor binding in chick optic tecta. PMID- 6269698 TI - Long term culture of bovine oligodendroglia isolated with a Percoll gradient. AB - Oligodendroglia were isolated from calf central nervous system (CNS) white matter by trypsinization in phosphate buffered saline and separation by centrifugation through Percoll. Using antisera to phenotypic markers and double labelling experiments we were able to identify essentially all cells in the cultures. The cells obtained were: (1) viable; (2) had intact plasma membranes and well preserved organelles, ribosomes and mitochondria; and (3) were greater than or equal to 95% oligodendroglia 16-20 h after isolation as determined by ability to bind antigalactocerebroside antibodies (anti-GalC). Oligodendroglia could be cultured for several weeks to months. Oligodendroglia established and maintained processes which bound anti-GalC. Myelin basic protein could be demonstrated in the cytoplasm of 40-60% of oligodendroglia cell bodies but not in the processes. PMID- 6269699 TI - Choline acetyltransferase activity in chick retina cultures: effect of membrane depolarizing agents. AB - The activity of choline acetyltransferase (CAT) was investigated in primary cultures of retina from 8-day-old chick embryos. After the second day in culture, the total and specific activities of the enzyme decreased by more than 50%. Cultivation of the cells in 56 mM K+ or 59 microgram/ml of veratrine retarded the loss of CAT activity up to days 3-5 in vitro. If the addition of 56 mM K+ or 59 microgram/ml of veratrine was delayed until the third day of culture, these agents had no effect on the remaining CAT activity. These results suggest that the survival in culture of a part of the cholinergic retinal neurons requires membrane depolarization. PMID- 6269700 TI - Increased [3H]glutamate receptor binding in aged rats. AB - Na-independent [3H]glutamate binding to rat hippocampal membranes increases progressively as a function of age. The increased binding represents an increased number of binding sites without changes in their apparent affinity for glutamate. However, [3H]glutamate binding, measured with a saturating concentration of calcium does not change at various ages. This does not reflect a change in the apparent affinity of calcium ions to stimulate [3H]glutamate binding, but a decrease in their maximal stimulatory effect. These results are discussed in relationship to age-related changes in certain physiological and behavioral functions. PMID- 6269701 TI - Effect of valproic acid on [3H]diazepam and [3H]dihydropicrotoxinin binding sites at the benzodiazepine-GABA receptor-ionophore complex. PMID- 6269702 TI - (-)-[3H]Dihydroalprenolol binding in subcellular fractions of rat cortex following noradrenergic denervation. AB - Two weeks after noradrenergic denervation, beta-adrenergic receptor binding increased in 2 of 3 crude fractions of rat cortical homogenates, while the relative distribution of binding was unchanged on continuous sucrose density gradients of the crude synaptosomal fraction. When rat glioma cells were fractionated by the same methods, a band of membranes with beta-adrenergic receptor binding sedimented at the same sucrose density as synaptosomes. Thus membrane receptors remained associated with synaptosomes even in the absence of noradrenergic nerve terminals suggesting that a portion of these receptors are either glial or associated with non-noradrenergic nerve terminals. PMID- 6269703 TI - Inhibition by lithium of dopamine receptors in rat prolactin release. AB - We investigated the effect of lithium on prolactin (PRL) secretion in both urethane-anesthetized rats and right atrial catheter-bearing conscious rats. Basal plasma PRL levels were not significantly altered for 4 h after lithium administration. However, lithium treatment apparently potentiated PRL release by haloperidol in both conscious and urethane-anesthetized rats. In addition, the inhibition by apomorphine of PRL secretion was significantly antagonized by lithium in conscious rats. Lithium had no effect on the enhancement of PRL secretion by either 5-hydroxytryptophan or beta-endorphin in conscious rats. These observations indicate that lithium affects PRL secretion when dopaminergic neural activity is altered. Therefore, it is possible to postulate that the decrease of dopamine receptor sensitivity by lithium may be related to the therapeutic action of the drug on affective disorders. PMID- 6269704 TI - Glial-released proteins: III. Influence on neuronal morphological differentiation. AB - In vitro model systems in neurobiology are available to detect and help characterize various intercellular development signals. The presence of such active substances in conditioned medium (CM) from rat C6 glioma cells (2BD clone) was examined using the pheochromocytoma-derived clonal cell lines PC12 and PCG2. Conditioned medium from C6 monolayers induces neurite outgrowth in PC12 cells and extensive alteration in PCG2 cell morphology by 24 h. This ability of CM was found (1) to remain after dialysis and lyophilization, (2) to be modulated by steroid treatment of C6 monolayers (PC12 cells only) and (3) to be distinct from the influence of NGF. Combinations of CM, nerve growth factor (NGF) and dibutyryl cyclic AMP when given together in pairs to PC12 or PCG2 cells revealed facilitation of neurite formation and cell morphology, respectively. These results suggest possible synergistic interaction between the three factors in the neuroglial regulation of neuronal morphological differentiation. PMID- 6269705 TI - The effects of intrathecal sympathomimetic agents on neural activity in the lumbar sympathetic chain of rats. AB - Intrathecal injections of norepinephrine (0.30 mumol) and clonidine (0.035 mumol) produced decreases in neural activity recorded from the lumbar sympathetic chain and caused changes in rat thermoregulation consistent with a reduction in efferent sympathetic activity. These results support the conclusion that bulbospinal noradrenergic pathways inhibit sympathetic outflow. The data also indicate that the spinal cord is a potential site of action for clonidine. PMID- 6269706 TI - Stress and beta-adrenergic receptor binding in the rat's brain. AB - The effect of acute and chronic electric shocks on beta-adrenergic receptor binding in the rat's brain was investigated. Beta-adrenergic receptor subsensitivity in the cortex was induced by chronic shocks, but not by acute shocks. This reduction appears to be due to a decreased number of receptors. It seems that stress, by increasing intrasynaptic norepinephrine levels resulting from an accelerated turnover rate, causes beta-adrenergic receptor subsensitivity. PMID- 6269707 TI - Phase changes induced by ketamine in the vertical vestibulo-ocular reflex in the rabbit. AB - The effect of ketamine has been tested on the phase of the vertical vestibulo ocular reflex of rabbits sinusoidally oscillated at various frequencies. A significant phase lag, predominantly affecting the macular component of the reflex, was observed. This action resembles that induced by Nembutal in the same preparation. A specific action of ketamine on synaptic transmission is suggested. Erroneous phase relationship between natural stimuli responses can be obtained in experiments employing ketamine. PMID- 6269708 TI - Alterations in rat central nervous system endorphins following transauricular electroacupuncture. AB - Auricular electro-stimulation (electroacupuncture) was found to produce naloxone reversible analgesia in the rat. These behavioral effects were accompanied by significant increases in cerebrospinal fluid (CSF) levels of endorphins with concomitant decreases in the basomedial hypothalamus and medial thalamus of beta endorphin-like immunoreactivity as well as endorphin-like radioreceptor activity. In addition, the radioreceptor assay also revealed a decrease in endorphin-like radioreceptor activity in the periaqueductal gray (PAG) matter. These results are interpreted to imply that electroacupuncture in the rat produces at least part of its analgesic action by activating central nervous system endorphinergic circuitry which results in a release and depletion of endorphins in certain brain loci and a concomitant elevation in the CSF. Hypophyseal endorphins do not appear to be involved in mediating acupuncture-induced analgesia in the rat since plasma levels of endorphins were not altered by this manipulation. PMID- 6269710 TI - GABA- and glycine-induced Cl- channels in cultured mouse spinal neurons require the same energy to close. AB - Fluctuation analysis has been used to study the influence of temperature on the conductance and mean open time of Cl- permeable ion channels induced by gamma aminobutyric acid (GABA) and glycine in the membrane of tissue cultured mouse spinal neurons. The conductance of GABA- and glycine-activated channels increased slightly at higher temperatures (Q10 approximately 1.3). The mean open times of these channels decreased at higher temperatures (Q10 approximately 3). Arrhenius plots for the open times of GABA- and glycine-induced channels were parallel and showed no obvious transition behavior over the temperature range 16-40 degrees C. PMID- 6269709 TI - Modulation of brain polyphosphoinositide metabolism by ACTH and beta-endorphin: structure-activity studies. AB - This study describes effects of ACTH1-24 and beta-endorphin on brain polyphosphoinositide metabolism in vitro. The interconversion of these polyanionic phospholipids was studied by incubation of a lysed synaptosomal fraction with [gamma-32P]ATP. Of the membrane phospholipids only PA, DPI and TPI became labeled. The reference peptide ACTH1-24 stimulated the formation of TPI and inhibited the production of PA. For effects on TPI formation both the sequences ACTH5-7 and ACTH10-16 were needed. Effects on PA formation required the sequences ACTH7-10 and ACTH10-16. The basic amino acids in ACTH10-16 seemed to be of crucial importance for the peptide effects. A stimulatory effect on DPI was visible when ACTH was shortened from the N-terminus, and the essential information was in ACTH7-10. beta-endorphin inhibited PA formation and this effect was abolished by C-terminal shortening to gamma-endorphin. Other fragments of the C-terminus of beta-LPH, including the enkephalins, were ineffective. It is concluded that the structure-activity relationship on TPI/PA formation correlates with a similar relationship obtained on excessive grooming behavior in vivo. A possible correlation between the effects on polyPI metabolism and opiate-like effects, and effects on extinction of active avoidance behavior in vivo is discussed. PMID- 6269711 TI - Wilms' tumor. PMID- 6269712 TI - Soft tissue sarcomas: classification and natural history. PMID- 6269713 TI - Case report: implantation of breast cancer in a transplanted nipple: a plea for preoperative screening. AB - A 45-year-old, white woman, following mastectomy for a large inflammatory carcinoma of the left breast with multiple involved nodes, had her nipple body banked in her left groin. She subsequently developed locally recurrent breast carcinoma in the areola of the transplanted nipple with metastases to the groin nodes, for which she received a radical groin dissection. Clinical and pathologic criteria for screening the nipples to be preserved are reviewed, and a plea is made for employing similarly stringent screens to eliminate future cases such as this. PMID- 6269714 TI - Brain stem glioma in childhood: acute hemiplegic onset. AB - Two children, age seven and 16 years, are described with the abrupt onset of a pure motor hemiplegia as the initial manifestation of a brain stem neoplasm. Subsequent rapid neurological deterioration localized the lesion to the brain stem and glioblastoma multiforme was diagnosed by surgical biopsy. It is suggested that brain stem gliomas with this unusual presentation are likely to be highly malignant and prone to rapid bulbar deterioration. PMID- 6269716 TI - Clostridium perfringens type C enteritis in a Quebec swine herd. PMID- 6269718 TI - An epizootic of swine influenza in Quebec. PMID- 6269717 TI - Alimentary tract manifestations of bovine adenovirus infections. AB - Two calves and a feedlot steer with systemic bovine adenovirus infection had hemorrhagic and necrotizing lesions confined to the digestive tract. In one calf there was severe, multifocal, necrotizing, hemorrhagic rumenitis, omasitis, abomasitis, enteritis and colitis. Small intestinal lesions were predominantly in Peyer's patches. Multifocal necrotizing abomasitis was the principal change in the other calf. Large amphophilic intranuclear inclusions typical of bovine adenovirus were common in swollen vascular endothelial cells. Bovine adenovirus was isolated from the former calf. The steer had diffuse hemorrhagic enterocolitis and large numbers of BAV inclusions in vascular endothelial cells of the intestinal lamina propria. Serum-neutralization tests to bovine adenovirus type 3 on acute and convalescent samples from six clinically affected in-contact animals revealed fourfold elevations in two. PMID- 6269715 TI - [Calf coronavirus neonatal diarrhea. A literature review (author's transl)]. AB - Calf coronavirus neonatal diarrhea. A literature reviewThe importance of the calf coronavirus in the etiology of neonatal diarrhea of calves has been reported many times from various countries. A literature review concerning this virus is presented in this paper. A detailed description of the pathogenesis, clinical signs and lesions of the disease, as well as the morphological, physicochemical, biological and antigenic characteristics of the virus are presented. The immunity of the calf against this virus and the principal diagnosis technics are also discussed. PMID- 6269719 TI - Hepatitis B virus profile of hepatocellular carcinoma in the Philippines. AB - The hepatitis B virus (HBV) profile was investigated in 104 age-grouped hepatocellular carcinoma (HCC) patients and 84 controls from the Philippines. The HCC-control percent positivities of the HBV parameters are: HBsAg: 70-18; anti HBs: 25-37; anti-HBs: 25-37; anti-HBc: 94-35; HBeAg: 5-2; anti-HBe: 60-30; HBV exposure rate: 97-57; current infection: 80-31. Male HCC anti-HBs positivity is significantly lower than in controls. Female HCC patients' anti-HBs are also lower than controls, but this difference is not statistically significant. Simultaneous presence of HBsAg and anti-HBs was found only in male HCC patients. The mean anti-HBc titer of anti-HBs-positive HCC is higher than that of controls. That of HCC patients negative for both HBsAg and anti-HBs is also higher than the corresponding controls. Anti-HBe positivities of infected and noninfected but previously exposed HCC patients are not significantly different, in contrast to noninfected previously exposed controls whose anti-HBe is lower than those with current infection. The exposure rate prevalence of current infection, and the antibody responses to HBV of HCC patients suggested a close relationship between the two conditions in the Philippines. PMID- 6269720 TI - Multiple biologic markers in the monitoring of treatment for patients with small cell carcinoma of the lung: the use of serial levels of plasma CEA and serum carbohydrates. AB - The monitoring utility of serial patterns of a single marker (carcinoembryonic antigen) level and multiple marker (three carbohydrates-fucose, mannose and galactose) levels in patients with small cell carcinoma of the lung was investigated using a quantitative approach. A serial multiple regression (SMR) model was formulated to assess the disease response following the first to the tenth course of therapy and resulted in the multiple correlations ranging from 0.183 (NS)-0.706 (P less than 0.005) for CEA, and 0.502 (P less than 0.250)-0.760 (P less than 0.025) for three carbohydrates, respectively. The appraisal of these markers utilizing the SMR model points out that: (1) the serial levels of CEA greater than 5.0 ng/ml are significantly correlated with the disease course whereas the serial levels less than 5.0 ng/ml reflect the trend of variation in the disease course, but with less accuracy; and (2) the levels of three carbohydrates, any one elevated before and during therapy, are significantly correlated with the disease course. PMID- 6269721 TI - Hypercalcemia complicating small-cell carcinoma. AB - Hypercalcemia is a common paraneoplastic syndrome complicating some varieties of lung cancer. It has rarely been reported with small-cell carcinoma of the lung. Seven cases of hypercalcemia complicating small-cell carcinoma of the lung are described; clinical features indicate that significant bone or bone marrow involvement is present in all cases. Parathormone assays were found to be generally in the normal range, though inappropriate for the levels of hypercalcemia. PMID- 6269722 TI - Biliary cystadenocarcinoma with peritoneal carcinomatosis. AB - An autopsy report of a patient with a hugh biliary cystadenocarcinoma arising in the right lobe of the liver is presented. The tumor had been though to be benign, but peritoneal carcinomatosis developed 18 months after the operation. Autopsy revealed marked peritoneal dissemination of mucinous adenocarcinoma, apparently a result of peritoneal seeding of hepatic cystadenocarcinoma, which was presumed to be triggered by cyst aspiration performed during the operation. Experience indicates that surgical procedures on cystic liver disease should be carried out carefully, considering the possible existence of malignancy. PMID- 6269723 TI - Final report on the United States Phase I Clinical Trial of the hypoxic cell radiosensitizer, misonidazole (Ro-07-0582; NSC #261037). AB - The hypoxic cell sensitizer misonidazole began phase I evaluation in the United States in July 1977. One hundred two patients received 104 individual courses of drug. Drug was administered from once to five times per week over time spans from one to six weeks. The individual doses ranged 1-5 g/m2, and 411 mean 4-6 hour serum levels were determined. The mean 4-6 hour serum level ranged from 30 micrograms/ml at 1 g/m2 to 183 micrograms/ml at 5 g/m2. The major toxicity noted was neurologic; 49% of evaluable courses showed peripheral neuropathy, and 9% of evaluable courses showed central nervous system effects and/or ototoxicity. In addition, 48 of 102 patients exhibited some degree of nausea and vomiting. The concomitant administration of dexamethasone and phenytoin sodium appeared to lower the incidence of neuropathy. Observations of efficacy were made comparatively in five patients who had multiple lesions treated with and without misonidazole. All five showed increased response in the lesions treated with misonidazole. It is concluded that misonidazole is a reasonably safe and potentially effective hypoxic cell sensitizer whose dose-limiting toxicity is neurologic. PMID- 6269725 TI - Human breast cancer: heterogeneity of estrogen binding sites. AB - A patient who had two primary tumors in the same breast is described. Both tumors were infiltrating duct carcinomas, but they differed as far as histologic malignancy and estrogen-receptor-positivity are concerned. One tumor was estrogen receptor-positive the other was estrogen-receptor-negative. The case illustrates the multicentric origin of breast cancer as well as its cellular heterogeneity. Problems of treatment are discussed. PMID- 6269724 TI - Induction of uterine cancer with inactivated herpes simplex virus, types 1 and 2. AB - A series of studies were performed to evaluate the oncogenic potential of inactivated herpes simplex viruses types 1 (HSV-1) and 2 (HSV-2) in the mouse cervix. HSV-1 or HSV-2 prepared in HEp-2 cell cultures and inactivated by exposure to formalin or ultraviolet light was applied to the mouse cervix for periods ranging from 20 to 90 weeks. Control mice were exposed for the same period to control fluids. Vaginal cytologic preparations from all animals were examined weekly to detect epithelial abnormalities. Animals were sacrificed and histopathological studies were carried out when cellular changes seen on vaginal smears resembled those indicative of premalignant or malignant changes as previously established in a similar model system using coal tar hydrocarbons. Other animals were exposed for periods up to 90 weeks, or until there was cellular evidence of invasive cancer. Cytologic and histologic materials were coded and evaluated without knowledge of whether they were from virus-exposed or control animals. Premalignant and malignant cervical lesions similar to those that occur in women were encountered in 78 to 90% of the virus-exposed animals. All controls were normal. Invasive cancer was detected in 24 to 60% of the animals and dysplasia was found in 18 to 66%. The yield of invasive cancer was twice as great after exposure to ultraviolet-inactivated HSV-2 as compared with formalin-inactivated virus. Various histologic grades of carcinoma of the cervix and endometrium were found. No primary lesions were found in the vagina or ovaries. PMID- 6269726 TI - Signet ring carcinoma of the female breast: a clinicopathologic analysis of 24 cases. AB - Signet ring carcinomas of the breast have been separated recently as an aggressive subtype of breast cancer, distinct from mucinous (colloid) carcinomas. Twenty-four cases of signet ring breast cancer (2% of total breast cancers at the authors' institution) were analyzed. The authors' study indicates that histogenetically such lesions are derived from lobular, not ductal, cells since mucin patterns and ultrastructural features are shared. In addition, in each of our 24 cases, infiltrating lobular carcinoma was identified; in 11 of these (46%) lobular carcinoma in-situ (LCIS) was also noted. Signet ring carcinomas show an unusual metastatic pattern with a propensity to involve serosal surfaces and mimicking gastrointestinal disease or retroperitoneal fibrosis. These tumors are associated with a poor prognosis, with 60% of our 24 patients dead of disease at 7 years. The distinctive clinical and pathologic features of signet ring carcinoma warrant separation of this group of tumors from other forms of breast cancer. PMID- 6269727 TI - Granulosa theca cell tumors in premenarchal girls: a clinical and pathologic study of ten cases. AB - Granulosa theca cell tumor (GTCT) in the premenarche accounted for 7% of all ovarian tumors treated at the Children's Hospital Medical Center from 1928 through 1979. The average age of the ten girls at the time of diagnosis was 5 years (range 11 months-121/2 years) with precocious "pseudopuberty" and an abdominal mass being the most common presentation. GTCTs were solitary (five right, five left) with an average diameter of 12.1 cm. Histologic examination showed a predominantly diffuse or solid pattern with prominent luteinization; Call-Exner bodies and folded ("coffee-bean") nuclei were inconspicuous. Ultrastructural examination of one GTCT confirmed the presence of both granulosa and theca components with the latter showing extensive luteinization; estradiol, testosterone and prolactin were demonstrated in the same tumor using immunologic techniques. The average follow-up time was 21 years with nine of the ten patients being followed for more than ten years. Salpingo-oophorectomy resulted in cures despite the occurrence of tumor spillage in two patients. The prognosis for GTCTs in the premenarche appears more favorable than for those occurring in adulthood, but further study is needed to completely define their full biologic potential; the significance of subsequent breast cancer in two long-term survivors merits further investigation as well. PMID- 6269728 TI - Cushing's syndrome secondary to a neuroendocrine tumor: relapse after bilateral adrenalectomy. AB - Bilateral adrenalectomy results in the removal of the site of glucocorticosteroid production thereby eliminating the signs and symptoms of Cushing's syndrome. A case is reported of a middle-aged man with Cushing's syndrome due to an ACTH producing tumor. The patient initially responded to adrenalectomy but had a fatal relapse. Autopsy showed that the right adrenal bed containing remnants of adrenal tissue. An islet cell carcinoma of the pancreas was thought to be the primary tumor. PMID- 6269729 TI - Hepatoma presenting as a retro-orbital metastasis. AB - Patients with hepatomas who present primarily with symptoms of metastatic disease are rare. A case is described of a patient whose initial manifestation of disease was related to a retro-orbital mass. The literature concerning orbital metastases is reviewed. PMID- 6269730 TI - Axillary-subclavian vein occlusion in patients with lung neoplasms. AB - Twelve patients with pulmonary neoplasms treated at the Fox Chase Cancer Center were found to have a syndrome of axillary-subclavian vein occlusion. Ten patients had non-small-cell lung carcinoma, one had small cell carcinoma, and one had mesothelioma. In eight patients, this vascular syndrome developed as a consequence of progressive or metastatic recurrent disease, while in four patients it presaged the appearance of the initial malignant disease. Axillary subclavian vein occlusion should be easily differentiated from the superior vena cava syndrome. Treatment with anticoagulation therapy in addition to specific antitumor therapy may relieve symptoms and signs without altering the occlusion itself. PMID- 6269731 TI - Quantitation of viral antigens released into plasma and culture fluids by murine mammary tumor cells. AB - Radioimmunoassay capable of measuring mouse mammary tumor virus (MMTV) 52,000 M.W. envelope glycoprotein (gp52) and 27,000 M.W. protein (p27) have been used to quantitatively compare plasma concentrations of these viral antigens in mice bearing spontaneous mammary tumors. Although gp52 was detected in the plasma of all tumor-bearing mice tested, p27 was detected in only a portion of tumor bearing animals. In p27-positive animals, gp52 was detected in higher concentrations than p27. These findings demonstrate that gp52 has preferential utility as a plasma marker for the presence of mammary tumors in MMTV-infected hybrid (BALB/c x DBA/8 F1), Paris RIII, and C3H/HeJ mice. In addition, cultures of MMTV-producing cells [GR-MMTV and MMTV(C3H)Fel I] were used as models to study the release of viral antigens in the absence of serum antibody or additional host factors. Comparisons of extracellular soluble and particulate antigen concentrations demonstrated that gp52 and p27 were present in substantially higher concentrations as soluble than virion-associated antigens. The mean ratio of non-virion-associated gp52 to virion-associated gp52 was 12.5:1 for GR-MMTV cells and 37.3:1 for MMTV(C3H)Fel I cells. The marked stability of MMTV in culture fluids suggested that virion breakdown was not responsible for the accumulation of soluble viral antigens in culture. The information obtained suggests that abundant virus-free antigens may be of greater use than virion associated antigens as a source of viral antigen to evaluate mammary tumor status. PMID- 6269732 TI - Collagen cell attachment protein from rat hepatoma cells. AB - This paper describes the isolation and partial characterization of a collagen cell attachment protein from the spent culture medium of rat hepatoma cells. When compared with serum fibronectin, this attachment protein differed in several biochemical parameters. The hepatoma attachment protein was partially purified by adsorbing and eluting from an inorganic gel, magnesium oxide. Cell adhesive activity may routinely recovered at levels of 10 to 30%, and a 2000-fold purification was attained. The hepatoma attachment protein was shown to be sensitive to trypsin and chymotrypsin, to be heat inactivated at 61 degrees, to have a molecular weight of 58,000, to have an isoelectric point of 4.1, to show an electrophoretic mobility on cellulose acetate of approximately one-half that of fibronectin, and not to cross-react with antifibronectin antisera. PMID- 6269733 TI - Early events during liver carcinogenesis involving two carcinogen:protein complexes. PMID- 6269734 TI - Differential sensitivity of normal and chemically transformed epithelial cells to cholera toxin. AB - We have been studying the regulation of growth by cyclic adenosine 3':5' monophosphate (cyclic AMP) and other factors in untransformed (K16) and chemically transformed (W8) rat liver epithelial cells. Initially, we found that 8-bromocyclic adenosine 3':5'-monophosphate was a more potent inhibitor of cell replication in K16 than in W8 cells. In addition, the phosphodiesterase inhibitor 1-methyl-3-isobutylxanthine (MIX) caused marked growth inhibition in K16 but not in W8 cells. Through the use of cholera toxin (CT) with or without MIX, we elevated intracellular cyclic AMP levels in a quantifiable fashion. With CT alone or combined with MIX, we observed a dose-dependent morphological change in W8 cells, which consisted of extensive "process" formation. K16 morphology was not altered at any concentration of CT +/- MIX tested. K16 cell growth was only marginally inhibited by CT alone, but markedly inhibited by CT plus MIX. W8 cell growth was moderately inhibited by CT alone or combined with MIX. Analysis of cyclic AMP levels revealed that, at all concentrations of CT +/- MIX and at all time periods tested, W8 cells produced significantly more cyclic AMP than K16 cells. It appears that morphological changes and growth inhibition are not necessarily linked and that MIX may inhibit K16 cell replication by means other than its ability to increase intracellular cyclic AMP levels. PMID- 6269735 TI - Binding of benzo(a)pyrene derivatives to specific proteins in nuclei of intact hamster embryo cells. AB - In hamster embryo cells incubated for 24 hr with 4 microM [3H]benzo(a)pyrene, a major portion of the nonextractable radioactivity in nuclear preparations copurifies with the protein fraction. When these proteins are analyzed by sodium dodecyl sulfate:polyacrylamide gel electrophoresis, significant variations in the labeling intensities of the various proteins are seen. Control experiments demonstrate that the labeling is due to covalent binding to protein. Histones H3 an H2A are heavily labeled while the other histones of the nucleosome core, H2B and H4, are devoid of radioactivity. Large amounts of label are associated with proteins with mobilities similar to the very lysine-rich histones H1. However, the results of differential extraction experiments suggest that the labeled proteins do not belong to either the H1 or the high-mobility-group class of chromosomal proteins. During 6 hr of inhibition of protein synthesis by cycloheximide, the metabolism of [3H]benzo(a)pyrene, as monitored by high pressure liquid chromatography, remained normal. Patterns of labelling of nuclear proteins after 3 or 6 hr were identical in the presence and absence of cycloheximide. This finding strongly suggests that binding of benzo(a)pyrene derivatives to nuclear proteins occurs in situ. PMID- 6269736 TI - Enzyme deviation patterns in primary rat hepatomas induced by sequential administration of two chemically different carcinogens. AB - Enzyme deviation patterns were examined in primary rat hepatomas induced by short term sequential administration of two chemical carcinogens from among 2 fluorenylacetamide (FAA), diethylnitrosamine (DENA), and 3'-methyl-4 dimethylaminoazobenzene (3'-Me-DAB) or by FAA or 3'-Me-DAB followed by phenobarbital as a promoter. The purpose was to discern how the patterns are influenced by different administration schedules of carcinogens and which of the two carcinogens in the sequence affects the pattern more. Biochemical differentiation of hyperplastic hepatic nodules and hepatomas was determined by simultaneous assays of activities and isozyme composition of glucose-adenosine triphosphate phosphotransferase, pyruvate kinase, glucose-6-phosphatase, fructose 1,6-bisphosphatase, and gamma-glutamyltransferase with consideration of histological classification of nodules and tumors. Poorly differentiated hepatomas were predominantly induced by 3'-Me-DAB followed by FAA or DENA except for hepatomas induced by 3'-Me-DAB followed by phenobarbital, which were mainly well and moderately differentiated; well and moderately differentiated hepatomas were predominantly induced by FAA followed by 3'-Me-DAB or phenobarbital. The degree of enzyme deviation of the hepatomas induced by DENA as the first carcinogen was intermediate between those of hepatomas induced by FAA or 3'-Me DAB, although the degree tended to increase with increased dose or term of DENA. These results indicate that deviations of some enzymes, such as pyruvate kinase and fructose-1,6-bisphosphatase, as well as histological differentiation of the primary hepatomas are more strongly influenced by the first carcinogen than by the second under our administration schedules and that the degree of enzyme deviation shown by hepatomas produced by a particular carcinogen treatment regimen principally related to the potential of that regimen to induce the more anaplastic tumors. PMID- 6269737 TI - Thyroid hormone receptors in human breast cancer. AB - Optimum conditions were established for preparation of nuclei from human breast cancer biopsies. Incubation of nuclei with various concentrations of L-3,3',5 [125I]triiodothyronine showed the presence of three binding systems: a high affinity binding system (type I) (KD approximately 0.5 micro M); an intermediate affinity saturable system (type II) (Kd approximately 0.5 micro M)p and a nonsaturable nonspecific system. Salt at high concentrations (0.4 M-KCl) extracted only type I triiodothyronine-binding protein, thus simplifying its study and quantification. Type I binding protein was shown to have the affinity for triiodothyronine and the hormonal specificity usually ascribed to thyroid hormone receptors. Its sedimentation coefficient was 3.6S at 0.4 M KCl. Extractable triiodothyronine receptors was measured in 58 individual biopsies of primary and metastatic breast cancer. It was present in all tumors, but its concentration was highly variable (average, 0.20 pmol/mg DNA; range 0.044 to 0.702). Triiodothyronine receptor concentration was not correlated with age or endocrine status of the patient or with extension or histological grading of the tumor. Moreover, there was no correlation with estradiol and progesterone receptor concentration. PMID- 6269738 TI - Blood group A-like glycolipid and a novel Forssman antigen in the hepatocarcinoma of a blood group O individual. PMID- 6269739 TI - [Changes in blood viscosity concomitant with prazosin therapy in patients with essential arterial hypertension]. PMID- 6269740 TI - Radionuclide evaluation of renal artery dilatation. AB - Radionuclide studies were sued in three patients to evaluate renal perfusion and function within 24 hours following transluminal dilatation. In one patient, technetium-99 m pertechnetate showed good renal perfusion one and 12 hours after a post-dilatation arteriogram had shown a renal artery intimal defect. Improved clearance of iodine-131 ortho-iodohippurate from the blood demonstrated an increase in renal function 18 hours following dilatation of a stenosis at a renal allograft anastomosis in the second patient, while technetium-99 m-labeled DTPA showed an improved total glomerular filtration rate 24-hours after dilatation of a saphenous vein bypass graft in the third patient. It was concluded that renal radionuclide studies are of benefit in evaluating patients in the immediate post dilatation period. PMID- 6269741 TI - Three different human tumor cell lines contain different oncogenes. AB - We have obtained foci of transformed mouse cells after transfection of human DNA from colon and bladder carcinoma cell lines and a promyelocytic leukemia cell line. These foci can be shown to contain a large number of human DNA sequences by use of highly repetitive human DNA sequence probes. Cell DNA from primary foci can be used in a subsequent cycle of transfection resulting in secondary foci that contain relatively little human DNA. Secondary foci appear to contain only the human sequences proximal to those responsible for the transformed phenotype. A set of characteristic DNA restriction fragments is found in common among secondary foci derived from each tumor cell line DNA. Comparison of the common DNA fragments found in secondary foci derived from three different human tumor cell lines indicates that these three cell lines contain three different transforming genes. PMID- 6269742 TI - The specific interaction of the Rous sarcoma virus transforming protein, pp60src, with two cellular proteins. PMID- 6269743 TI - SV40 gene expression is modulated by the cooperative binding of T antigen to DNA. AB - We analyzed the DNA binding properties of wild-type simian virus 40 large T antigen and found that the protein binds cooperatively to three tandem sites at a regulatory region of SV40 DNA. One consequence of this T antigen:DNA interaction is the specific repression of SV40 early RNA synthesis in vitro. We mapped a region of 85 base pairs that is necessary and sufficient to initiate early SV40 transcription in vitro. This promoter region lies directly adjacent to the third T antigen binding site but does not include that "TATA" sequence. To determine how T antigen interacts with its binding sites to repress RNA synthesis, we analyzed transcription directed by a variety of wild-type, mutant and hybrid template DNAs. Our findings suggest that the cooperative binding of T antigen to its sites is directly responsible for inhibiting the initiation, rather than blocking elongation, of early RNA synthesis. A model is presented to explain the role of T antigen binding in the regulation of viral transcription and DNA replication during SV40 lytic infection. PMID- 6269744 TI - Analysis of transcriptional regulatory signals of the HSV thymidine kinase gene: identification of an upstream control region. AB - We have identified a transcriptional control region of the herpes simplex virus tk gene. This finding results from in vivo transcription assays of specific deletion mutants constructed in vitro. A region located between 40 and 100 nucleotides upstream from the putative transcription start site of the tk gene can promote transcription by RNA polymerase form II in the complete absence of the mRNA-coding component of the gene. When the region is deleted enzymatically from a 5' direction, accurate transcriptional expression is reduced by a factor of 50. The small remaining level of accurate transcription is eliminated by deletion of sequences from 32 to 16 nucleotides upstream from the the structural gene. It appears that the sequences between 16 and 32 nucleotides upstream from the 5' terminus of the tk gene are required to specify the exact start site of transcription. Control of both the efficiency of transcription and rough specification of the position of initiation, however, depends on sequences 40- 100 nucleotides upstream from the tk structural gene. PMID- 6269745 TI - Ribosomal insertion-like elements in Drosophila melanogaster are interspersed with mobile sequences. AB - Sequences homologous to the type 1 ribosomal DNA insertion occur in the chromocenter and in one location on the fourth chromosome of Drosophila melanogaster. Ribosomal insertion-like elements frequently occur in the form of tandem repeats and are often interspersed with nonhomologous DNA. Sequences that interrupt of flank insertion-like elements are members of diverged repeated DNA families. Members of five of these interspersed sequence families are located at multiple euchromatic sites as well as in the chromocenter. The euchromatic sites differ greatly in the gt-1 and gt-X11 stocks of D. melanogaster, suggesting that these sequence families are mobile in the genome. No long inverted repeats were detected in any of these interspersed sequences. One sequence, called 101F, interrupts a ribosomal insertion-like element; the nucleotide sequences across the boundaries between 101F and ribosomal insertion have been determined. A stretch of 13 base pairs that is present once in the ribosomal insertion is repeated at the ends of the 101F sequence, suggesting a target site duplication. Within the 101F element, no extended direct or inverted repeat sequence exists. The interspersed repeated sequences studied are transcribed into rare, heterogeneous, poly(A)-lacking nuclear RNA molecules. In one case, we showed that both strands of a flanking sequence are transcribed, but to a different extent. With respect to structural features and the nature of their transcripts, the sequences described here are distinct from other known transposable elements in Drosophila. PMID- 6269746 TI - An extensive deletion causing overproduction of yeast iso-2-cytochrome c. AB - CYC7-H3 is a cis-dominant regulatory mutation that causes a 20-fold overproduction of yeast iso-2-cytochrome c. The CYC7-H3 mutation is an approximately 5 kb deletion with one breakpoint located in the 5' noncoding region of the CYC7 gene, approximately 200 base from the ATG initiation codon. The deletion apparently fuses a new regulatory region to the structural portion of the CYC7 locus. The CYC7-H3 deletion encompasses the RAD23 locus, which controls UV sensitivity and the ANP1 locus, which controls osmotic sensitivity. The gene cluster CYC7-RAD23-ANP1 displays striking similarity to the gene cluster CYC1-OSM1-RAD7, which controls, respectively, iso-1-cytochrome c, osmotic sensitivity and UV sensitivity. We suggest that these gene clusters are related by an ancient transpositional event. PMID- 6269747 TI - Avian reticuloendotheliosis virus: identification of the hematopoietic target cell for transformation. AB - Non-virus-producing hematopoietic cells transformed in vitro by reticuloendotheliosis virus (REV-T) induce lethal "reticuloendotheliosis" when inoculated into histocompatible chickens. This is the first direct demonstration that an in vivo target cell of an avian acute leukemia virus can be transformed in vitro. The tumorigenic, REV-T-transformed non-virus-producing cells fail to express helper-virus-coded proteins. REV-T transformed tumorigenic cells therefore do not require helper-virus functions. Cells transformed in vivo or in vitro by REV-T have lymphoblastoid morphology and express low levels of terminal deoxynucleotidyl-transferase activity and bursal-cell determinants. One clone synthesized Ig mu. The preferred target cells for REV-T transformation are therefore immature lymphoid cells that express B-cell determinants. We propose that the unique transforming sequence of REV-T be designated rel (lymphoid). PMID- 6269748 TI - A steady state model for analyzing the cellular binding, internalization and degradation of polypeptide ligands. PMID- 6269749 TI - A position-effect control for gene transposition: state of expression of yeast mating-type genes affects their ability to switch. AB - Mating-type switches of the yeast Saccharomyces cerevisiae occur by unidirectional transposition of copies of unexpressed mating-type genetic information, residing at HML and HMR loci, into the expressed MAT locus. The HML and HMR loci remain unchanged. In contrast, in appropriate strains where the silent loci are also allowed to express, for example in mar mutants, efficient switches of HML and HMR are shown to occur at rates equivalent to those observed for MAT. Thus the position-effect control on the direction of transposition is affected by the state of expression of the locus under study the expressed loci switch regardless of their location. PMID- 6269750 TI - Cloning and characterization of the integrated viral DNA from three lines of SV40 transformed mouse cells. AB - Recombinant DNA techniques have been used to isolate the integrated viral DNA, together with flanking cellular sequences, from three independently isolated lines of SV40-transformed BALB/c 3T3 cells. We have determined the structures of these cloned segments and their relationships to one another by restriction enzyme mapping, electron microscopic heteroduplex analysis and transfer hybridization experiments. Our data indicate that the structure of the integrated viral DNA is consistent with the idea that integration involves a tandemly repeated intermediate, that extensive amplification and rearrangement of viral and adjacent cellular sequences occurs after integration and that the majority of viral DNA insertions do not contain an intact early transcription unit. The altered templates presumably encode the truncated and super T antigens found in these cells. Either they are interrupted in the middle of the early region, in which case they generally retain the region in which tsA mutations map, or they contain tandem duplications of the tsA region. Further structural analysis will allow the prediction of the precise structures of these unusual T antigens, and the availability of the corresponding templates opens the way to an analysis of the functions of these proteins. PMID- 6269751 TI - Fine structure of the origin-proximal DNAase I-hypersensitive region in wild-type and EC mutant polyoma. AB - The chromatin of wild-type polyoma virus displays a unique DNAase I highly sensitive region in situ in the infected nuclei, extending for about 260 nucleotides from the origin of replication to the beginning of the late region. We show that this highly sensitive region is not homogeneous. It displays a well defined pattern of differential sensitivity along its 260 nucleotides, including one protected subregion and two hypersensitive sites, which concern a unique residue or very few nucleotides. All these features were mapped to a precision of +/- 5 bp relative to the DNA nucleotide sequence. In parallel, we studied a PyEC mutant, whose sequence is grossly rear-ranged in this very region. This allows the PyEC to overcome the block in the expression of the early genes in the mouse embryonal carcinoma PCC4 cell line. We show that this mutant, however, displays an identical highly sensitive region with the same fine structure. The mapping of this structure on the mutant nucleotides sequence coincides with that of the wild type relative to any arbitrary point on the late side of the rearrangement; however, 60% of the mutant molecules display this unique local chromatin structure, instead of 20% for the wild-type ones. Finally, the sequence determinism of this singularity is discussed, as well as its possible role in the control of the early transcription and the establishment of the PyEC phenotype.. PMID- 6269752 TI - Arrest of segregation leads to accumulation of highly intertwined catenated dimers: dissection of the final stages of SV40 DNA replication. AB - When SV40-infected cells are placed into hypertonic medium, newly synthesized DNA accumulates as form C catenated dimers. These molecules consist of two supercoiled monomer circles of SV40 DNA interlocked by one or more topological inter-twinings and are seen as transiently labeled inter-mediates during normal replication. Form C catenated dimers represent pure segregation intermediates, replicative DNA structures in which DNA synthesis is complete but which still require topological separation of the two daughter circles. Hypertonic shock seems to block selectively a type II topoisomerase activity involved in disentangling the two circles. This is reflected in the fact that form C catenated dimers that accumulate during the block are highly intertwined with catenation linkage numbers up to C(L) = 20. While initiation of replication is also inhibited by hypertonic treatment, ongoing SV40 DNA synthesis is not affected, and replication is free to proceed from the earliest cairns structure through to form C catenated dimers. The block to segregation is rapidly and completely released by shifting the cells back to normal medium. A much slower recovery of DNA segregation takes place on prolonged incubation in hypertonic medium, perhaps because of some cellular homeostatic mechanism. The results of this work lead to a detailed view of the final stages of SV40 DNA replication. PMID- 6269753 TI - Cloning of DNA sequences from the white locus of D. melanogaster by a novel and general method. AB - We describe the isolation of a cloned DNA segment carrying unique sequences from the white locus of Drosophila melanogaster. Sequences within the cloned segment are shown to hybridize in situ to the white locus region on the polytene chromosomes of both wild-type strains and strains carrying chromosomal rearrangements whose breakpoints bracket the white locus. We further show that two small deficiency mutations, deleting white locus genetic elements but not those of complementation groups contiguous to white, delete the genomic sequences corresponding to a portion of the cloned segment. The strategy we have employed to isolate this cloned segment exploits the existence of an allele at the white locus containing a copy of a previously cloned transposable, reiterated DNA sequence element. We describe a simple, rapid method for retrieving cloned segments carrying a copy of the transposable element together with contiguous sequences corresponding to this allele. The strategy described is potentially general and we discuss its application to the cloning of the DNA sequences of other genes in Drosophila, including those identified only by genetic analysis and for which no RNA product is known. PMID- 6269754 TI - A copy of the copia transposable element is very tightly linked to the Wa allele at the white locus of D. melanogaster. AB - Results are described demonstrating that several X chromosomes of Drosophila melanogaster carrying the Wa (white-apricot) mutant allele also carry homology to the copia transposable element in distal 3C of the polytene chromosome map as assessed by situ hybridization. The locus of the Wa mutation, white, resides in distal 3C. We further show, using fine scale genetic mapping techniques, that the copia homology in distal 3C in Wa-bearing chromosomes is very tightly linked to the Wa mutation. Both the Wa mutation and the copia homology associated with it map to the central portion of the white locus. PMID- 6269755 TI - Transposon-mediated site-specific recombination: a defined in vitro system. AB - Transposition of the insertion element gamma delta is thought to involve formation of intermediates in which the element is present at each junction between donor and target replicons. In vivo these cointegrate structures are rapidly converted to the end products of transposition by site-specific recombination at a defined sequence, res, that is present in each directly repeated gamma delta element. Resolvase, an element encoded protein of molecular weight 21,000 is required for cointegrate resolution. I have demonstrated site specific recombination in vitro using purified resolvase and a cointegrate analog substrate. The required components of the system described here are resolvase, negatively supercoiled substrate DNA, buffer and Mg2+. Neither host-encoded products nor high energy cofactors appear to be required for resolution in vitro. Catenated, resolved molecules are the major products of the reaction. Elimination of Mg2+ from the reaction yields different product molecules. The in vitro system described here provides an opportunity for detailed study of the resolution reaction. PMID- 6269756 TI - Transposon-mediated site-specific recombination in vitro: DNA cleavage and protein-DNA linkage at the recombination site. AB - Resolvase, the product of the tnpR gene of the transposable element gamma delta, mediates a site-specific recombination between two copies of the element directly repeated on the same replicon. The resolution site, res, at which resolvase acts lies in the intercistronic region between the tnpA and tnpR genes. We have studied this site-specific recombination in vitro. In the absence of Mg2+, a resolvase-res complex is formed, which contains DNA molecules that have been cleaved at res. Our data suggest that in this complex resolvase is covalently attached to the 5' ends of the cleaved DNA, leaving free 3' hydroxyl groups. DNA cleavage is stimulated by the interaction of two res sites on the same substrate molecule and appears to be an intermediate step in normal res site recombination. We show that the DNA is cut within a region previously identified as containing the crossover point at the palindromic sequence 5'- (see formula in text) to generate 3' extensions of two bases. PMID- 6269757 TI - Promoter for a developmentally regulated gene in Bacillus subtilis. AB - We have determined the nucleotide sequence of the promoter for aB. subtilis gene (the 0.4 kb gene) whose transcription is under developmental control. Transcription of the 0.4 kb gene is turned on at the onset of sporulation; this RNA synthesis depends on the products of the B. subtilis regulatory genes (the spoO loci) that control the initiation of development. Recognition of the 0.4 kb gene promoter in vitro is dictated by novel species of B. subtilis RNA polymerase sigma factor known as sigma 37 and sigma 29 but not by the principal B. subtilis sigma factor sigma 55. Using S1 nuclease mapping, runoff transcription and dinucleotide priming, we have identified dual startpoints (separated by about 10 bp) for sigma37-directed transcription of the 0.4 kb gene These start-points correspond closely to the 5' termini of 0.4 kb RNA synthesized in vivo during the course of sporulation. Two forms of sigma37 containing RNA polymerase were distinguished that preferentially utilize either the upstream or the downstream startpoint in vitro. We investigated the requirements for sigma37-directed transcription by constructing in vitro deletion mutations that extend from the upstream direction into the 0.4 kb promoter region. One such deletion, which terminates 40 and 51 bp upstream from the transcription startpoints (thereby removing a highly AT-rich 26 bp sequence), completely eliminates transcription from the downstream startpoint but only partially inhibits transcription from the upstream startpoint. A second deletion that terminates at the upstream startpoint completely prevents transcription from both initiation sites. The implications of 0.4 kb gene promoter structure for developmentally regulated transcription of B, subtilis are discussed. PMID- 6269758 TI - The mitochondrial genome is large and variable in a family of plants (cucurbitaceae). AB - The genome sizes of mitochondrial DNA from darkgrown (etiolated) shoots of several higher plants were determined by reassociation kinetics and restriction analysis. Kinetic complexities obtained from reassociation kinetics measured spectrophotometrically indicate a mitochondrial genome size of 1600 Md for muskmelon, 1000 Md for cucumber, 560 Md for zucchini squash and 220 Md for watermelon (four species in the cucurbit family), as well as 240 Md for pea and 320 Md for corn. The kinetic curves also reveal the presence (except in corn) of sequences of a few magadaltons of complexity, reiterated about 10-50 times and representing 5%- 10% of the DNA in each mitochondrial genome. Molecular weight summation of fragments resulting from digestion with restriction endonucleases Sal I and Kpn I give genome size estimates similar to those obtained from reassociation kinetics, except for muskmelon and cucumber, for which the large number of fragments of similar size limits our estimate to at least 500 Md. The number of mitochondrial genomes per diploid cell is estimated to be about 110 to 140 for muskmelon, zucchini and watermelon. We consider the possible evolutionary mechanisms by which the mitochondrial genome has grown within the cucurbit family and the possible reasons for the existance of a seven to eight-fold range in mitochondrial genome size among such closely related species. PMID- 6269759 TI - Superoxide anion and hydrogen peroxide production by chemically elicited peritoneal macrophages--induction by multiple nonphagocytic stimuli. PMID- 6269760 TI - Demonstration of actin filaments in sponge cells. PMID- 6269761 TI - Translational diffusion in the plasma membrane of single cells as studied by fluorescence microphotolysis. PMID- 6269762 TI - [Changes of the sinusoid hepatic blood flow after food ingestion: decline in patients with stenosis of the splanchnic vessels (author's transl)]. PMID- 6269763 TI - [Some problems concerning the evaluation of modern contra-ulcerous drugs. Comparison of four medicaments suppressing gastric acidity (author's transl)]. PMID- 6269764 TI - [Androblastoma in pregnancy]. PMID- 6269766 TI - [Possibilities and limitations of sialographic examination in childhood: clinical contribution]. PMID- 6269765 TI - The role of lipid peroxidation in CCl4-induced damage to liver microsomal enzymes: comparative studies in vitro using microsomes and isolated liver cells. AB - The question as to whether CCl4 decreases the activities of glucose-6-phosphatase and cytochrome P-450 in liver endoplasmic reticulum mainly through its action in stimulating lipid peroxidation has been investigated using Promethazine to block lipid peroxidation. The investigation, moreover, has compared the effects of CCl4, with and without Promethazine, on isolated rat hepatocytes with corresponding effects on rat liver microsomal suspensions. Our data give no support for the view that products of lipid peroxidation are the main cause of the decrease in cytochrome P-450 observed in CCl4-intoxication. However, our present results are consistent with lipid peroxidation being a major contributory factor to the decrease in glucose-6-phosphatase activity observed in CCl4-induced liver injury. PMID- 6269768 TI - [Measles in Abidjan. Apropos of 500 cases]. PMID- 6269767 TI - [Granular cell myoblastoma of the vulva (case report)]. PMID- 6269769 TI - A case for preplanned thoracic and prophylactic whole brain radiation therapy in limited small-cell lung cancer. AB - Thirty patients with previously untreated limited small-cell lung cancer were treated in a prospectively randomized trial comparing chemotherapy versus chemotherapy plus prophylactic whole brain radiation therapy. Without preplanned thoracic radiation therapy in addition to the chemotherapy, 78% of patients failed in the lung (52% in the lung solely) as the first site of treatment failure. In those patients not receiving prophylactic whole brain irradiation, 73% failed in the CNS at the time of first and second failure versus 13% of the group randomized to prophylactic whole brain radiation therapy (and those two before the radiation was given). A strong case can be made for the use of both preplanned thoracic and prophylactic whole brain radiation therapy in conjunction with combination chemotherapy, at least until much more effective chemotherapy is found. PMID- 6269770 TI - An evaluation of low-dose cisplatin as part of combined modality therapy of limited small cell lung cancer. AB - Sixty-two patients with previously untreated limited stage small cell lung cancer were treated in a prospectively randomized trial comparing thoracic irradiation plus combination chemotherapy with VP-16-213, vincristine (Oncovin), cyclophosphamide, and Adriamycin (VOCA) or those same four drugs plus low-dose (40 mg/m2) cisplatin (VOCAP). The addition of the cisplatin in eight courses of planned chemotherapy did not significantly improve either time to tumor progression of survival or alter sites of disease progression. It did, however, worsen the degree and frequency of nausea, vomiting, and myelosuppression. We did not identify any benefit from the usage of low-dose cisplatin as employed in this study. PMID- 6269771 TI - Zinostatin and doxorubicin. A combination phase I study. AB - Because of encouraging single-agent activity for both zinostatin and doxorubicin in hepatocellular cancer, a phase I tolerance study with these drugs in combination was undertaken. The dose of zinostatin given daily for 5 consecutive days and repeated every 6 weeks was fixed at 2250 units/M2. The starting dose of doxorubicin was 45 mg/m2 on days 1 and 22 of every 6-week cycle, but this was escalated or deescalated by increments of 33% as tolerated. The occurrence of unpredictable severe and prolonged cumulative myelosuppressive toxicity in most patients resulted in considerable management difficulties. In addition, three patients developed congestive heart failure at cumulative doxorubicin doses ranging from 195 to 270 mg/m2 and two patients developed possible drug-related nephrotoxicity. Until reasons for the pharmacogenetic variability observed with zinostatin are defined, combination studies employing this drug are not recommended. PMID- 6269772 TI - Comparisons of the effects of chemical carcinogens in mixed cultures of rat hepatocytes and human fibroblasts. AB - Unscheduled DNA synthesis (UDS) was measured simultaneously in rat hepatocytes and human fibroblasts when combined cultures of the 2 cell types were exposed to procarcinogens. Human fibroblasts were preincubated with 5-bromo-2'-deoxyuridine (BRdU) to substitute for thymidine in the DNA. Hepatocyte DNA was separated from the heavier BRdU-substituted fibroblast DNA by isopycnic centrifugations in neutral cesium chloride and the specific activities of the DNA's were determined. In the presence of hepatocytes, benzo - [a]pyrene (BP) induced more UDS in the fibroblasts than in the hepatocytes. BP induced no UDS in the fibroblasts in the absence of hepatocytes. Diethylnitrosamine (DEN) and 2-acetylaminofluorene (AAF) stimulated a significant amount of UDS only in the hepatocytes. Thus, the co cultures of hepatocytes and fibroblasts responded with UDS to these chemical carcinogens in a manner that parallels the tissue specificity of the carcinogenicity of these chemicals in vivo. That is, the known hepatocarcinogens DEN and AAF, only stimulated significant UDS in the hepatocytes, whereas the non hepatocarcinogen, BP, though activated in these cultures mainly by the hepatocytes, stimulated more UDS in the fibroblasts than in the hepatocytes. The amount of [3H]BP bound to DNA was investigated in the co-cultures and in cultures of fibroblasts alone. When co-cultures were exposed to [3H]BP the fibroblast DNA had approximately 3 times more BP bound to it (per microgram DNA) than did the hepatocyte DNA. The amount of [3H]BP bound to the DNA of cultures of fibroblasts alone was 29% of the amount bound to the DNA of the fibroblasts from the co cultures. Thus, although the hepatocytes were mainly responsible for the activation of BP, more [3H]BP was bound to the fibroblast DNA. It is suggested that the intercellular distribution of carcinogenic metabolites may be a significant determinant of the carcinogenic effect. PMID- 6269773 TI - Biliary excretion, systemic availability and reactivity of metabolites following intraportal infusion of [3H]benzo[a]pyrene in the rat. AB - Following the intraportal infusion of [3H]benzo[a]pyrene (BP) at two dose levels (5 and 0.125 mumol/kg) in the rat, metabolites were excreted via the bile and were released into the hepatic venous blood. At each dose level, a significant portion (approx. 15-18%) of biliary metabolites was directly extractable with ethyl acetate and a total of approx. 24-32% became extractable after incubation of bile with beta-glucuronidase. More than 65% and 70% of the 3H in blood and liver, respectively, was directly extractable with ethyl acetate. The h.p.l.c. profile of extracted metabolites was found to differ at the two dose levels studied. The binding of reactive metabolites to hepatic protein and DNa was measured at four dose levels of [3H]BP. The possible availability of hepatic derived metabolites to extra-hepatic sites is discussed. PMID- 6269774 TI - Metabolism of chemical carcinogens by cultured human and rat bladder epithelial cells. AB - The metabolism of benzo[a]pyrene, aflatoxin B1, N-nitrosodimethylamine, N nitrosoethylmethylamine, and N-nitrosopyrrolidine has been studied in cultures of normal human and rat urinary bladder epithelial cells. The cultures were incubated with radioactively labeled carcinogens for 24 h, and the metabolism was assayed by binding of reactive metabolites to DNa and by the release of metabolites into the medium. Only slight variation in binding level of benzo[a]pyrene to DNa among the three human bladder cell lines was seen, the level of binding being higher than to rat DNA. The major benzo[a]pyrene-DNA adduct (80%) in human bladder cells eluted prior to the adducts formed by reaction of 7,8-dihydroxy-9,10-epoxy - 7,8,9,10-tetrahydrobenz[a]pyrene with guanine by high pressure liquid chromatography, but has yet to be identified. The benzo[a]pyrene-DNA adducts were quickly removed and only about 10% of the radioactivity remained associated with human bladder DNA 72 h post-treatment with benzo[a]pyrene. The 7,8- and 9,10-diols of benzo[a]pyrene were the major organo soluble metabolites formed by both rat and human bladder cells. The primary benzo[a]pyrene metabolites were conjugated to a minor extent only. The highest level of modification of DNA was seen in the case of N-nitrosodimethylamine. N Nitrosopyrrolidine was oxidized in both the alpha-and beta-position by all three cell lines, the oxidation at the alpha-position being predominant. No binding to DNA was detectable with N-nitrosoethylmethylamine, although this compound was metabolized as measured by the formation of CO2 and aldehydes. These results add the urinary bladder to the list of human organs which have been shown to metabolize chemical carcinogens into electropositive metabolites. However, qualitative differences exist between the data from bladder cells and those from other human organs. PMID- 6269775 TI - Enhanced reactivation of ultraviolet-damaged herpes virus in ultraviolet pretreated skin fibroblasts of cancer prone donors. AB - An enhanced reactivation of ultraviolet-damaged (u.v. at 254 nm) unclear replicating double-stranded DNA viruses occurs when corresponding host cells are treated with radiation or carcinogens prior to infection. This phenomenon seems to be due to an induced DNA repair activity the nature of which is yet unknown. The u.v.-induced enhanced reactivation (ER) of u.v.-damaged herpes simplex virus (u.v. - HSV) was compared in dividing skin fibroblasts of 30 donors either normal or afflicted by genetic disorders, some of which confer a high risk for sunlight induced skin cancers. Cultures were exposed to a single dose of 1.0-25 J.m-2 from 0-60 h before infection with u.v.-HSV (at about 10-3 survival) and the rate of viral production was determined. ER was maximal for a 36 h time interval in all lines. The u.v. dose eliciting maximal ER was 15 J.m-2 in fibroblasts from normal donors, xeroderma pigmentosum (XP) heterozygotes, Mibelli's porokeratosis, diffused naevomatosis, Down's syndrome, xerodermoids, XP variants and epidermodysplasia verruciformis. However, in the latter 3 cases, ER was almost 10 times more pronounced than in the normal cases. The u.v. dose eliciting maximal ER was 0.1, 0.3 and 2 J.m-2 in excision deficient XP fibroblasts from groups A, D and C, respectively, 2.5 J.m-2 in 11961 fibroblasts and 5 J.m-2 in fibroblast lines from cockayne s syndrome. PMID- 6269776 TI - Early cellular responses in vitro to endotoxin administration. AB - The sequence of early events which follow the administration of E coli lipopolysaccharide (LPS) to cultured mouse neuroblastoma (C-1300) cells was investigated. Emphasis was placed on cellular energy metabolism in order to establish whether or not an energy failure occurred and whether it was a primary or a secondary effect. Exposure of cultured neuroblastoma cells to LPS produced rapid changes in the regulatory parameters of energy metabolism, an oxidation of intramitochondrial pyridine nucleotides, and a decline in cellular [ATP]/[ADP] [Pi], which were followed by alterations in mitochondrial morphology. In spite of the changes in individual parameters at early stages of exposure to LPS, the cellular energy producing systems remained tightly controlled and the rate of ATP synthesis was maintained at a constant and undiminished level. This allowed the cells to preserve their ionic gradients as manifested by high intracellular [K+] and unaltered transmembrane electrical and pH gradients. These early changes in mitochondrial metabolism were not accompanied by detectable leakage of mitochondrial matrix enzymes into the cytosol, which indicated that mitochondrial membrane remained intact. After longer exposure to LPS, the rate of ATP synthesis declined, the mitochondrial membrane became permeable to high molecular weight substances (matrix enzymes), and intracellular [K+] began to decrease (K+ leakage). It was concluded that responses of mitochondrial metabolism are one of the early events in endotoxemia. PMID- 6269777 TI - Effect of EHDP on calcium accumulation and technetium-99m pyrophosphate uptake in experimental myocardial infarction. PMID- 6269779 TI - Liquid-chromatographic assay of angiotensin-converting enzyme in serum. AB - This assay of angiotensin-converting enzyme is based on release of hippuric acid from a synthetic tripeptide, hippuryl-L-histidyl-L-leucine. Hippuric acid is separated and quantitated on a reversed-phase column under conditions similar to those used for assay of theophylline and acetaminophen. The method is rapid and free from interferences. PMID- 6269778 TI - Measurement of amniotic fluid surfactant. AB - Measurement of the production of surfactant is the most direct means of prenatally assessing fetal pulmonary maturity. We review assays which have evolved for measuring surfactant, classifying them into two general categories: biochemical quantitation and biophysical measurements. Biochemical quantitation assays include the amniotic fluid lecithin/sphingomyelin ratio and quantitation of lecithin and other surfactant phospholipids. Biophysical measurements include measurement of surface-tension-lowering ability of extracts of amniotic fluid lipid and evaluation of surface-tension-related properties such as foam stability and microviscosity. Assays of surfactant are subject to certain pre-analysis sources of variation over which the analyst has no control, such as variability in total in vivo amniotic fluid volume, incomplete in vivo mixing of surfactant with amniotic fluid, and presence of contaminating blood or meconium. We also examine other factors such as centrifugation speed and time, and storage of the amniotic specimen before analysis. These factors can dramatically affect analyses, and must be carefully controlled by the analyst. In general, both biochemical and biophysical approaches to surfactant analysis are useful diagnostically. When properly performed, both approaches give results that correlate well, both with each other and with clinical outcome. Because "mature" and "immature" values overlap, none of the assays can completely eliminate false predictions, whether of fetal maturity or fetal immaturity. PMID- 6269780 TI - Normal acid-phosphatase and angiotensin converting enzyme activities in serum of a patient with Gaucher's disease. PMID- 6269781 TI - Revised values of the paH of monosodium 1,4-piperazinediethanesulfonate ("Pipes') in water and other buffers in isotonic saline at various temperatures. PMID- 6269782 TI - A highly sensitive fluorimetric assay for pyridoxal phosphate phosphatase. AB - A highly sensitive fluorimetric assay for pyridoxal phosphate phosphatase is described. The assay involves separation of the substrate and product by ion exchange chromatography followed by treatment of pyridoxal with potassium cyanide under slightly alkaline conditions to form 4-pyridoxolactone, a highly fluorescent compound. Certain kinetic properties of the enzyme activities in human neutrophils are described. PMID- 6269783 TI - Kinetic alteration of the K+ -sensitive p-nitrophenylphosphatase in red cell membrane from beta-thalassemic patients. PMID- 6269784 TI - Distribution of virus antibody activity among human IgG subclasses. AB - Human IgG subclass antibody activity against viruses was studied by separating the IgG3 fractions from sera exhibiting high titres for rubella, polio types I, II and III, and herpes I viruses. The sera were fractionated on DEAE Affi-Gel Blue and protein A-Sepharose CL-4B columns using specific subclass antisera for identification. All IgG3 fractions exhibited a molecular weight of 164,000 daltons, a pI mean of 8.21 and S20,W1% = 6.2 as determined by polyacrylamide gel electrophoresis, isoelectric focusing and analytical centrifugation. Quantitative determination of the individual subclass concentrations by nephelometry showed them to be within the biological norm. The concentration and distribution of IgG in the sera and that of the IgGl, -2 and -4 and IgG3 fractions were used as a basis for studying antiviral activity. The IgG3 fractions showed a greater ratio of IgG concentration to antibody titre than the IgGl, -2 and -4 fractions as determined in neutralization and haemagglutination inhibition tests. The IgG3 fraction from anti-rubella serum bound 96.6% 125I-labelled rubella virus (HP 77/DE5). The IgG 3-125I-rubella immune complex was separated over a protein A Sepharose CL-4B column and confirmed with subclass-specific antisera in radial immunodiffusion plates. Individual Gm allotype analyses showed markers distributed as follows: G3m(5,-6,10,11,13,-16,21,-24) for all the serum donors indicating similar genotypic expression of IgG3s. PMID- 6269785 TI - Effects of 1,24 dihydroxyvitamin D3 and calcitonin on fracture healing in adult rats. AB - Calcitonin and 1.25(OH)2D3 have opposite effects on the serum concentrations of Ca and P, as well as on bone resorption, and can be observed in the process of healing of standardized fracture in adult rats. The rats given 1.25(OH)2D3 had a stronger fracture callus and slightly less pronounced postfracture osteopenia. Calcitonin did not significantly influence the fracture healing but had a pronounced effect in preventing the osteopenia. The effects of 1.25(OH)2D3 are believed to be indirect, i.e., through the changes in the serum Ca X P product, whereas the osteopenia preventing action of calcitonin may come from direct effect on bone. PMID- 6269786 TI - Effects of caffeine withdrawal on isoproterenol-stimulated cyclic adenosine monophosphate. AB - The effect of short-term caffeine withdrawal on lymphocyte beta-adrenoceptor sensitivity was studied in seven men who had been drinking coffee daily for at least 3 mo before the study. The ratio of cyclic adenosine monophosphate production after in vitro incubation with isoproterenol and a blank was used to assess receptor sensitivity. There was a reduction in sensitivity to isoproterenol but not to prostaglandin E1 3 days after caffeine withdrawal. The mechanism of this effect is not clear, but may represent a biochemical correlate of caffeine-withdrawal syndrome. PMID- 6269787 TI - Long-term anticonvulsant therapy and intestinal calcium absorption. AB - Twelve patients on anticonvulsant therapy were studied to determine whether or not the drugs induced alterations in gastrointestinal absorption of calcium, response to parathyroid hormone (PTH), or serum 25-hydroxy vitamin D (25-OHD) concentrations. Fractional calcium absorption (FCaA) was determined by giving 45Ca intravenously and orally. The short-term response to PTH was assessed by giving 200 U of parathyroid extract (PTE) intravenously over 15 min and measuring hourly urine cyclic adenosine monophosphate (cAMP) and tubular reabsorption of phosphate (TRP). Calcemic response to PTH was followed by giving intramuscular injections of PTE, 200 U every 6 hr. FCaA was 30.8 +/- 3.7% lower than the normal of 42.2 +/- 2.5% (P less than 0.025), and baseline 25-OHD levels were 30.5 +/- 3.4 ng/ml (normal 15 to 50 ng/ml). Anticonvulsant drugs did not alter renal response to PTE. There was a rise in urinary cAMP from 3.7 +/- 0.23 to 6.1 +/- 0.47 mumol/gm creatinine (P less than 0.005) with a fall in TRP from 87.8 +/- 1.2% to 78.8 +/- 1.6% (P less than 0.005). Serum calcium rose from 9.4 +/- 0.1 to 11.1 +/- 0.3 mg/dl (P less than 0.005). We conclude that FCaA is low in patients receiving anticonvulsant drugs, even when serum 25-OHD levels and the response of bone and kidney to PTH remain normal. PMID- 6269788 TI - Ranitidine kinetics and dynamics. I. Oral dose studies. AB - Ranitidine, an H2-receptor antagonist, has been shown to reduce pentagastrin stimulated gastric secretion. We examined the relationship between inhibition of gastric secretion and ranitidine serum concentration. Twelve normal male subjects received 20, 40, or 80 mg of ranitidine orally 90 min before starting a 3-hr continuous infusion of pentagastrin, 2 micrograms/kg/hr. Ranitidine, 20, 40, and 80 mg, reduced hydrogen ion output by 29%, 50%, and 70% and secretion volume by 21%, 37%, and 47%. Pepsin activity was reduced by 8%, 50%, and 49% by the same doses. Peak serum concentration was correlated positively with percent reduction in hydrogen ion output (r = 0.81, P less than 0.001) and volume (r = 0.71, P less than 0.01) over a 2-hr period. A 50% inhibition of hydrogen ion output was associated with a peak ranitidine serum concentration of 165 micrograms/l and subjects reached peak serum concentration 60 to 120 min after oral dosing. An appropriate therapeutic effect should be achieved with 8 hourly doses of 80 mg ranitidine. No clinically significant subjective or toxic biochemical effect of ranitidine was seen after single doses. White blood cell count was reduced in 11 of 12 subjects 7 days after ranitidine, an observation which calls for further investigation. PMID- 6269790 TI - Prostacyclin: homeostatic regulator or biological curiosity? PMID- 6269789 TI - Ranitidine kinetics and dynamics. II. Intravenous dose studies and comparison with cimetidine. AB - Intravenous ranitidine has been shown to reduce pentagastrin-stimulated gastric secretion. Eight normal men received, in randomized order, 60 mg ranitidine or 300 mg cimetidine intravenously over 2 min. Both ranitidine and cimetidine induced decreases in volume hydrogen ion content and pepsin activity of stimulated gastric juice. Ranitidine half-life (t1/2) was 2.1 +/- 0.1 hr and cimetidine (t1/2) was 1.5 +/- 0.1 hr. Ranitidine volume of distribution was 1.6 +/- 0.1 l/kg and that of cimetidine was 1.12 +/- 0.12 l/kg. The clearance of ranitidine was 0.54 +/- 0.04 l/kg hr-1 and that of cimetidine was 0.5 +/- 0.05 l/kg hr-1. It is suggested that the intravenous loading dose of ranitidine necessary to attain a serum concentration of 200 micrograms/l (which would achieve a 50% inhibition of gastric acid) is 0.3 mg/kg, followed by an infusion rate of 0.11 mg/kg hr-1. PMID- 6269791 TI - Plasma levels of vitamin D metabolites in diphosphonate-treated rats. AB - 1. Protein-binding assays have been used to measure plasma 1,25-dihydroxy-vitamin D [1,25-(OH)2D] as well as 25-hydroxy-vitamin D [25-(OH)D] in rats given 10 mg of phosphorus (P) day(-1) kg(-1) as ethane-1-hydroxy-1,1-diphosphonate (EHDP). 2. In control animals given a normal laboratory chow plasma 25-(OH)D and 1,25-(OH)2D were about 40 nmol/l and 300 pmol/l respectively. 3. EHDP produced a decrease of plasma 1,25-(OH)2D to below 50 pmol/l in 2 days. 4. Both in control and in EHDP treated rats plasma 1,25-(OH)2D increased when dietary calcium (Ca) was restricted to 0.1%, or dietary P to 0.2%, indicating that the well-known stimulatory effect of Ca or P deprivation was at least partially effective in EHDP-treated rats. 5. In response to an increase of the oral supply of vitamin D3 to 65 nmol/day the plasma level of 25-(OH)D rose in both control and EHDP groups. Plasma 1,25-(OH)2D was not increased above the normal value in control rats. In EHDP-treated rats, however, plasma 1,25-(OH)2D rose to a level equal to that in controls, suggesting that the effect of EHDP on plasma 1,25-(OH)2D can be overcome at high precursor concentration. PMID- 6269792 TI - Calcium efflux and steroid output from superfused rat adrenal cells: effects of potassium, adrenocorticotropic hormone, 5-hydroxytryptamine, adenosine 3':5' cyclic monophosphate and angiotensins II and III. PMID- 6269793 TI - [Clinical experience with a new antihypertensive drug (captopril SQ 14.225), an oral inhibitor of converting enzyme]. PMID- 6269794 TI - [Crohn's disease: review of the acquisitions and problems of etiopathogenesis, histogenesis and therapy]. PMID- 6269795 TI - Nutritional needs of the aged. PMID- 6269796 TI - A study in calves of an immunologic relationship between herpes simplex virus and Bovid herpesvirus 2. PMID- 6269797 TI - Release of some staphylococcal enzymes and toxins under the influence of size of inoculum and time of incubation. PMID- 6269798 TI - A micro-enzyme-linked immunosorbent assay (ELISA) test for detection of feline leukemia virus in cats. PMID- 6269799 TI - Mice inoculated with Marek's disease tumor cells: increased number of lymphomas. PMID- 6269800 TI - In vitro blastogenic responses of peripheral lymphocytes from marmosets to phytohemagglutinin and to autologous lymphocytes transformed by Epstein-Barr virus. PMID- 6269801 TI - In vitro and in vivo immune responses in neonatally thymectomized Holstein Friesian calves exposed to bovine viral diarrhea virus. PMID- 6269802 TI - Renal cortical necrosis. Experimental induction by hormones. PMID- 6269803 TI - Priming of influenza viral RNA transcription by capped heterologous RNAs. PMID- 6269804 TI - Splicing and the regulation of viral gene expression. PMID- 6269805 TI - Regulation of viral transcription and DNA replication by the SV40 large T antigen. PMID- 6269806 TI - Warts--a clinical's view. AB - We do have more modalities for treating warts than ever before, but the very plurality of approaches bespeaks the fact that no single method is adequate. We await the development of a safe and effective wart vaccine with keen anticipation. PMID- 6269807 TI - Ultrastructural changes in gamma-irradiated Aspergillus flavus spores. AB - Ultrastructural changes in gamma-irradiated Aspergillus flavus were investigated. Electron microscopic studies revealed lipid-like inclusions, aggregated in the spore lumen near the cell membrane in the radiation-induced mutants. Their absence in the parent strain may indicate their direct significance in aflatoxin production. PMID- 6269809 TI - Comparison of proliferation and cytopathogenicity of swine vesicular virus and coxsackievirus B5. AB - Sequential appearance of both swine vesicular disease virus and Coxsackievirus B5 antigens in a pig kidney cell line was studied by immunofluorescence and electron microscopy. The replication cycle of each virus was approximately 3-4 h. Viral antigens were demonstrable in the cytoplasm 2 h after inoculation. A compact mass of fluorescence was seen when cells showed cytopathogenic effect at 5.5 h. After 3 h, a few viral particles, seen by electron microscopy, were in the cytoplasm. Morphological changes of cells occurred at the same time. Cytoplasmic crystalline arrays of virus were first detected at 7 h. PMID- 6269808 TI - Ultrastructural changes induced by steroids and gonadotropins in cultured rat Sertoli cells. AB - Testicular cells readily grew in cultures of seminiferous tubule fragments derived from adult rat testes. They formed confluent monolayers and continued to grow through four passages. The majority of cells had ultrastructural features characteristic of Sertoli cells. They exhibited large nuclei lacking heterochromatin, having nuclear membrane clefts, prominent nucleoli, significant amounts of agranular endoplasmic reticulum, large and numerous mitochondria, and lipid droplets. Cultured Sertoli cells responded to follicle-stimulating hormone (FSH), androgens, and dbcAMP by undergoing distinct morphological and ultrastructural changes. FSH induced parallel arrays of granular endoplasmic reticulum. Testosterone and dbcAMP resulted in the swelling of mitochondria, the formation of parallel cristae that stretched across the lumen, and the appearance of lipid droplets. Sertoli cells, cultured in a medium containing testosterone and FSH since their initiation, developed extensive agranular endoplasmic reticulum, strikingly large lipid droplets, and mitochondria that were characterized by either a dark matrix and vesicular cristae, or a light matrix and parallel cristae. These results indicate that Sertoli cells respond in vitro to hormones that are active in vivo, and support the suggestion that the Sertoli cell is a site of steroid synthesis in the mammalian testis. PMID- 6269810 TI - Glucose dissimilation in Entamoeba histolytica. AB - The endproducts of glucose dissimilation in Entamoeba histolytica were found to be carbon dioxide, acetate and ethanol. This organism possesses the same Embden Meyerhof intermediates as found in most investigated organisms. In its glucose-to pyruvate pathway several unusual features were demonstrated. The pyruvate-to acetate and pyruvate-to-ethanol pathways are also unique as compared with that of other organisms. The distinctive properties of the metabolic enzymes provide the basis for the development of new chemotherapeutic agents against this parasitic protozoa. PMID- 6269811 TI - [Glomus tumor of the bone]. PMID- 6269812 TI - Influence of angiotensin converting enzyme inhibition with captopril on blood pressure and adrenergic function in normal and sodium restricted rats. AB - Observations with both captopril and teprotide suggest interplay of the renin angiotensin and sympathetic nervous systems during sodium depletion. We therefore examined adrenergic responses in normal or sodium restricted (8 days low sodium chow; trichlormethiazide 3 mg/kg, p.o., days 5-7) normotensive rats orally pretreated with placebo and captopril (3 or 10 mg/kg; twice on day 7, once on day 8) and pithed 2 hrs after the last dose. Consistent hypotension in conscious intact animals was observed only in sodium-depleted groups receiving captopril. Pressor responses to low frequency (2.5 Hz--5 sec) sympathetic stimulation and phenylephrine were reduced in normal sodium, pithed normotensive Sprague-Dawley rats receiving 10, but not 3 mg/kg captopril and low sodium animals receiving both doses. Suppression of phenylephrine by captopril was accentuated in sodium depleted groups. Pressor responses to angiotensin II were less in all salt depleted animals receiving either placebo or captopril. Captopril failed to reduce tachycardia to either sympathetic nerve stimulation or isoproterenol. These effects of captopril suggest that angiotensin plays a role in maintenance of vascular, but not cardiac adrenergic function. This role is manifested at a post-junctional site and becomes critical in the sodium deficient state. PMID- 6269813 TI - Granular cell myoblastoma of the sigmoid colon. AB - A granular cell myoblastoma of the upper sigmoid colon is reported in a 53-year old male. The tumor was detected during investigation of abdominal pain and was removed by colonoscopic polypectomy. Colonoscopy provides a new method of treatment for these unusual colonic lesions and avoids the need for surgery. To our knowledge the tumor has not been reported previously in the sigmoid colon. PMID- 6269814 TI - [Cloning and restriction analysis of the DNA BamHI-EcoRI fragment containing genes of the hsd-region in Escherichia coli]. PMID- 6269815 TI - [Cloning of a portion of the genome of the Moloney mouse sarcoma virus containing the oncogen]. PMID- 6269816 TI - [Hypothetical phosphile-thiol molecular mechanism of Na+/K+- and Ca2+ pump functioning in biomembranes]. PMID- 6269817 TI - [Small nucleosome as a possible structural element of chromatin detectable by Ca, Mg-endonouclease]. PMID- 6269819 TI - [Analysis of the acetylcholine noise in mammalian sympathetic ganglion neurons]. PMID- 6269820 TI - [Synthesis of double-stranded RNA in the isolated microsomes of hen cells infected with Rous sarcoma virus]. PMID- 6269818 TI - [Possible mechanism of the potentiating action of glucocorticoids in relation to catecholamines in the heart]. PMID- 6269821 TI - [Kinetics of the incoming sodium current in perfused neurons governed by the transmembrane gradient of osmotic pressure]. PMID- 6269822 TI - [Picosecond spectroscopy of porphyrin-Ni(II) complexes. Excited electron states and the photodissociation of axial ligands]. PMID- 6269823 TI - Ketoconazole--an antifungal drug for oral use. PMID- 6269824 TI - Potential value of cefoperazone in bacterial meningitis: experimental studies. AB - To assess the potential value of cefoperazone in treating bacterial meningitis, its pharmacokinetics in the cerebrospinal fluid of rabbits were studied. Cefoperazone penetrated poorly into the cerebrospinal fluid of rabbits with uninflamed meninges, but in the presence of meningitis concentrations increased 2 to 3-fold. These concentrations were above the minimum inhibitory concentrations for the majority of Enterobacteriaceae, indicating the potential value of cefoperazone in treating bacterial meningitis. The half-lives of cefoperazone and moxalactam in cerebrospinal fluid, measured by a bioassay, were marked prolonged by meningeal inflammation. In contrast, the half-life of cefotaxime in cerebrospinal fluid was short. Consequently both cefoperazone and moxalactam provided significantly better antibacterial effect in cerebrospinal fluid than did cefotaxime. PMID- 6269825 TI - [Denervation and re-innervation processes, electrological diagnosis and therapy]. PMID- 6269826 TI - Changes in prostaglandin binding capacity to single oviductal smooth muscle cells after ovulation in the rabbit. PMID- 6269827 TI - Triiodothyronine nuclear receptor in chick embryo: nature and properties of hepatic receptor. PMID- 6269828 TI - Effects of catecholestrogens on luteinizing hormone levels in long tem ovariectomized adult rats. AB - The long term ovariectomized adult rat was used to test the effects of exogenous estradiol, 4-hydroxyestradiol, and 2-hydroxyestradiol on LH secretion. To this end, different doses of estradiol 3-benzoate, 4-hydroxyestradiol 3,4-dibenzoate, and 2-hydroxyestradiol 2,3-dibenzoate were injected daily at 0800 h, and the LH serum levels were measured on 4 experimental days. At a dose of 1 micrograms/day, estradiol benzoate lowered LH secretion, beginning 48 h after the first injection (morning of day 2), and induced a characteristic LH surge 10 h later. 4 Hydroxyestradiol dibenzoate at the same dose produced less suppression of LH on the morning of day 3, but caused a comparable and highly significant surge on the same evening. Higher doses (3 and 10 micrograms/day) resulted in the same pattern seen with estradiol benzoate. 2-Hydroxyestradiol dibenzoate at comparable doses had no effect. Only extremely high doses (129 micrograms/day) caused slight suppression of tonic LH secretion 72 h after the first injection, and inconsistent LH elevations occurred on the same evening. It is concluded that in this model, catecholestrogens act as estrogens with respect to LH suppression and release, with 4-hydroxyestradiol being a potent estrogen and 2-hydroxyestradiol a weak estrogen. PMID- 6269829 TI - Doubly radioiodinated luteinizing hormone: preparation and characterization. AB - Bovine [131I]Iodo-alpha LH-[125I]iodo-beta LH (**LH) has been prepared and shown to be physically and biologically equivalent to unmodified hormone. The beta subunit was modified with 125I, purified by adsorption to Concanavalin A Sepharose and elution with methylmannoside, added to alpha-subunit, and allowed to reassociate to intact hormone. Iodination with 131I was then carried out in the reassociation mixture and **LH was isolated by gel filtration. Both gel electrophoresis and rechromatography on Sephadex G-100 showed that both radiolabels comigrated with unmodified hormone. Sodium dodecyl sulfate gel electrophoresis showed that 131I was found in the alpha-subunit and 125I in the beta-subunit; this result is in agreement with studies by others which show that the tyrosines of the beta-subunit are nonreactive in intact hormone. In receptor binding assays, both radiolabels were specifically displaced in a similar fashion by LH. Scatchard analysis showed high affinity binding (Ka approximately equal to 1.5 X 10(10) M-1) for both labels. Comparison of receptor-binding activity with steroidogenic activity showed that iodinated hormone molecules not only bound to receptor but also stimulated testosterone production. The demonstration that full biological activity is retained with iodination in both subunits shows that such doubly labeled LH can be used to monitor the disposition of both subunits simultaneously during interaction of the hormone with target cells. PMID- 6269830 TI - Differential steroidogenic enzyme activities in different populations of rat Leydig cells. PMID- 6269831 TI - Evidence for acute inhibitory effects in vivo of 1 alpha-hydroxycholecalciferol on parathyroid hormone secretion in rats. AB - In an attempt to elucidate the influence of 1 alpha-hydroxycholecalciferol (1 alpha OHD3) on parathyroid hormone (PTH) secretion, sequential measurements were made of 1) serum calcium and urinary excretion of cAMP in conscious perfused rats, and 2) serum calcium in nephrectomized rats; also, the effects of a single iv injection of 1 alpha OHD3 on these parameters were examined. In conscious perfused rats, 6.25 micrograms/kg (15 nmol/kg) 1 alpha OHD3 reduced the urinary excretion of cAMP (approximately 40% of the initial value; P less than 0.05), which reached a level compatible with that of parathyroidectomized rats at 4 h; this fall was sustained for 24 h. Serum concentrations of calcium (total and ionized) did not change at 6 h, and increased at 24 h. In parathyroidectomized rats which were continuously infused with bovine PTH (0.75 U/h), the vitamin D preparation had no significant effect on the urinary excretion of cAMP. Nephrectomy, followed by an injection of the vehicle (0.05 ml 99.5% ethanol), induced a transient hypercalcemia (13.12 +/- 0.39 mg/dl at 6 h). This hypercalcemic response was prevented by prior parathyroidectomy. Injections of 1.25 and 6.25 micrograms/kg 1 alpha OHD3 caused a significant suppression of the hypercalcemia (P less than 0.05 and P less than 0.1, respectively) in the presence of parathyroid glands, whereas a dose-related hypercalcemic effect was observed in their absence. These results suggest that in rats, 1 alpha OHD3, either directly or most probably after conversion into 1 alpha, 25 dihydroxycholecalciferol, 1) acutely inhibits PTH secretion without causing a significant rise in serum calcium, and 2) suppresses PTH secretion in secondary hyperparathyroidism induced by nephrectomy. PMID- 6269832 TI - Naloxone has a direct effect on the adrenal cortex. PMID- 6269833 TI - Enkephalin and blood-brain barrier: studies of binding and degradation in isolated brain microvessels. PMID- 6269834 TI - Studies on the bioactivity of radioiodinated highly purified bovine thyrotropin: analytical polyacrylamide gel electrophoresis. AB - Highly purified bovine TSH (stored in solution at -70 C) was radioiodinated by the stoichiometric chloroamine-T method. The iodinated material ws subjected to analytical polyacrylamide disc gel electrophoresis. TSH was eluted from gel slices (1 mm width) and was analyzed for radioactivity and bioactivity. The latter was determined using the cultured thyroid cell cAMP response assay. Radioactivity in the TSH preparation migrated separately from bioactivity, but concordant with the protein bands observed in gels run in parallel. Further studies performed on bovine TSH purified in our laboratory, as well as on a different TSH preparation of exceptionally high potency (both stored as lyophilized powder) revealed a different pattern, with TSH bioactivity and radioactivity eluting concurrently. Iodination of TSH did not alter its electrophoretic migration on disc gel electrophoresis. In all preparations polymorphism of TSH bioactivity was observed, with at least four separate protein bands containing TSH bioactivity being present in our preparation. The relationship between the degree of iodination and retention of TSH bioactivity was examined. Incorporation of 125I into TSH was greatly different at two different concentrations of chloramine-T. Despite this, however, the progressive loss of TSH bioactivity was similar at both concentrations, indicating that incorporation of iodine into the TSH molecule is not itself responsible for the decrease in bioactivity. These studies indicate variability among different TSH preparations in terms of their retention of bioactivity. Significant loss of TSH bioactivity appears to occur during storage in solution. The damage to the biological activity of TSH during the iodination procedure is more likely related to the oxidation process than to the incorporation of iodine. PMID- 6269835 TI - Influence of cell density on desensitization of the thyroid cell cyclic adenosine 3',5'-monophosphate response to thyrotropin stimulation. PMID- 6269836 TI - Hormone-induced homologous and heterologous desensitization in the rat adipocyte. AB - We examined the process of desensitization in the isolated rat adipocyte. When adipocytes were exposed to isoproterenol (10(-7) or 10(-5) M) or ACTH (250 mU/ml) for 2 h, there was a marked decline of as much as 77% in response upon restimulation by hormone, as measured by glycerol release or cAMP levels. This desensitization was both heterologous as well as homologous. Thus, for example, exposure of adipocytes to isoproterenol desensitized them to further stimulation by both isoproterenol and ACTH. The process was time dependent, since augmentation rather than desensitization was seen if cells were initially exposed to hormone for 30 min rather than 2 h. No desensitization was seen when the cells were restimulated with the nonhormonal lipolytic agent dibutyryl cAP. Similarly, no desensitization was seen when cells were first exposed to dibutyryl cAMP and then restimulated with hormone. We draw the following conclusions. First, desensitization in the adipocyte is a time- and dose-dependent process that is specific for adenylate cyclase-activating hormones. Secondly, the process is heterologous as well as homologous. Initial exposure of the adipocyte to one adenylate cyclase-activating hormone reduces its adenylate cyclase or lipolytic response upon reexposure to either the same or a different adenylate cyclase activating hormone. Finally, the reduction in the end result of hormone activation, lipolysis, is due in part to a decrease in inducible levels of cAMP. PMID- 6269838 TI - An assessment of Leydig cell function after bilateral or unilateral efferent duct ligation: further evidence for local control of Leydig cell function. AB - Leydig cell function was examined in adult male rats at 2 and 4 weeks after bilateral or unilateral efferent duct ligation. Bilateral efferent duct ligation resulted in significantly elevated serum LH levels, an increased size of Leydig cells and an enhanced testosterone response to gonadotropin stimulation in vitro despite a marked loss of LH-hCG receptors. After unilateral ligation of the vasa efferentia, the parameters of Leydig cell function in the ligated testes showed identical changes to those seen after bilateral ligation, whereas such changes were minor or absent in the unligated contralateral testes of the same animals. These results demonstrate that the modifications of Leydig cell function after efferent duct ligation are mainly due to local changes within the testes providing further evidence for an intratesticular control of Leydig cell function. PMID- 6269837 TI - Mineralocorticoid receptors in rat anterior pituitary: toward a redefinition of "mineralocorticoid hormone". AB - There is increasing evidence that a pituitary factor(s) in addition to ACTH can influence aldosterone secretion. By analogy with glucocorticoids and ACTH, such a factor(s) may be under mineralocorticoid negative feedback control, presumably via specific mineralocorticoid receptors. We here report studies in which mineralocorticoid receptors in the anterior pituitary are described and clearly distinguished from glucocorticoid receptors. Pituitary mineralocorticoid receptors closely resemble those previously reported in rat kidney and salivary gland in terms of their affinity for aldosterone, the hierarchy of affinities they display for other steroids, and their sedimentation values on sucrose density gradients. PMID- 6269839 TI - Effects of chronic intermittent immobilization stress on rat testicular androgenic function. AB - In rats, chronic intermittent immobilization stress induced a drastic fall in the plasma concentration and testicular content of testosterone (T) without detectable changes in plasma LH values. In vitro basal T production by interstitial cell-enriched preparations from stressed rats and the responses to hCG, dibutyryl cAMP, or choleratoxin were suppressed, while cAMP production was not modified. The increase in plasma T concentrations in control animals was identical after the in vivo injection of 5, 10, or 50 IU hCG, while stressed rats failed to respond to 5 IU, but showed a response similar to that of control animals with 10 and 50 IU. These results suggest that chronic intermittent immobilization stress decreases Leydig cell sensitivity to gonadotropins. PMID- 6269840 TI - Dissociation of serum triiodothyronine concentration and hepatic nuclear triiodothyronine-binding capacity in streptozotocin-induced diabetic rats. AB - To determine the relationship between the concentrations of serum T3 and hepatic nuclear T3 receptor in a reversible nonthyroidal disease, we studied these parameters in rats with streptozotocin-induced diabetes mellitus, control rats, and rats that were weight-matched to the diabetic rats by food restriction. Results were similar either 1 or 9 weeks after the induction of diabetes. A significant decrease from control in mean serum T4, T3 and free T3 index was noted in the diabetic rats. However, mean serum TSH was not altered significantly. The hepatic nuclear T3-binding capacity in the diabetic rats was similar to that in the control at both time intervals, whereas the nuclear T3 binding capacity of fasted rats was decreased. The dissociation of serum T3 and hepatic nuclear receptor concentrations in diabetic rats suggests that receptor concentration is not modified by thyroid hormones in this nonthyroidal disease. PMID- 6269841 TI - Photoaffinity labeling of luteinizing hormone releasing hormone receptor of rat pituitary membrane preparations. AB - Specific LHRH receptor proteins of plasma membrane preparation from pituitary glands of the rat were identified using an 125I-labeled photoreactive LHRH derivative, [D-Lys6-N epsilon-azidobenzoyl]LHRH. This analog retained high binding affinity (apparent Kd value of 0.1 nM) to a single class of receptors. Sodium dodecyl sulfate polyacrylamide gel electrophoresis indicated the specific photolabeling of two proteins, a major band with an apparent molecular weight of 60,000 daltons and a minor band of 48,000 daltons. The latter is probably a degradation product of the receptor. PMID- 6269842 TI - Ca2+ transport by intact synaptosomes: the voltage-dependent Ca2+ channel and a re-evaluation of the role of sodium/calcium exchange. AB - The verapamil-sensitive Ca2+ channel in the synaptosomal plasma membrane is investigated. Verapamil is without effect on Ca2+ uptake or steady-state content in synaptosomes with a polarized plasma membrane, but completely inhibits the additional Ca2+ uptake following plasma-membrane depolarization by high [K+], by veratridine plus ouabain or by high concentrations of the permeant cation tetraphenylphosphonium. Verapamil-insensitive Ca2+ influx and steady-state content are identical in polarized and depolarized synaptosomes, even though the Na+ electrochemical potential is greatly decreased in the latter, indicating that Na+/Ca2+ exchange is not a significant mechanism for Ca2+ efflux under these conditions. A transient Na+-dependent Ca2+ efflux can only be observed on addition of Na+ to Na+-depleted depolarized synaptosomes. While 0.2 mM verapamil decreases the ate of 86Rb+ efflux and 22Na+ entry during depolarization induced by veratridine plus ouabain, the final steady-state Na+ accumulation is not inhibited. Ca2+ efflux from synaptosomes following mitochondrial depolarization does not occur by a verapamil-sensitive pathway. PMID- 6269844 TI - Nucleosidediphosphate kinase associates with rings but not with assembled microtubules. AB - Microtubules reassembled in vitro from chick brain contain significant nucleosidediphosphate (NDP) kinase activity (EC 2.7.4.6) although the specific activity decreases with successive cycles of reassembly. However, while the recovery of microtubule protein, as a function of initial protein concentration, exhibits a critical concentration below which there is no polymerisation, the recovery of NDP kinase activity is, at low initial protein concentrations, directly proportional to the initial protein content indicating that microtubule protein and the kinase activity are independently recovered. This was confirmed by pelleting the reassembled microtubules through a sucrose cushion: the specific activity of the pelleted microtubules was reduced by approximately 90%. By contrast, when cold-dissociated microtubule protein, which is predominantly in the form of rings, is fractionated on a Biogel A 15 m column the microtubule protein and NDP kinase activity coeluted in the void volume and the specific activity remained constant throughout the ring fraction. Similarly, when microtubules were dissociated in the presence of NDP kinase the enzyme bound to the generated rings. These results suggest that NDP kinase binds preferentially to the rings compared with the microtubules, and a model is proposed to account for the presence of this enzyme in pellets of microtubule protein. PMID- 6269843 TI - The effects of Mg2+ on the Ca2+-binding properties and Ca2+-induced tyrosine fluorescence changes of calmodulin isolated from rabbit skeletal muscle. AB - Calmodulin from phosphorylase kinase (the delta subunit) was obtained as a homogeneous protein in a spectroscopically pure form, and its interaction with Ca2+ and Mg2+ was studied. 1. Determination of the binding of Ca2+ to calmodulin in a buffer of low ionic strength (0.001 M) show that it contained six binding sites for this divalent cation. 2. Employment of a buffer of high ionic strength (0.18 M) allowed two Ca2+/Mg2+-binding sites (KdCa2+ = 4.0 microM), which showed Ca2+ - Mg2+ competition (KdMg2+ = 0.75 mM), to be distinguished from two Ca2+ specific binding sites (KdCa2+ = 40 microM). The remaining two Ca2+-binding sites are not observed under these conditions and are probably Mg2+-specific binding sites. Thus, the binding sites on calmodulin are remarkably similar to those of the homologous Ca2+-binding protein, troponin C [Potter and Gergely (1975) J. Biol. Chem. 250, 4628, 4633]. 3. The conformational states of calmodulin are defined by Ca2+, Mg2+ and salt concentrations, which can be differentiated by their Ca2+ affinity and their relative tyrosine fluorescence intensity. In a buffer of high ionic strength, Mg2+ induces a conformation which enhances the apparent affinity for Ca2+. Addition of Ca2+ leads to an enhancement of the tyrosine fluorescence intensity, which remains enhanced even upon removal of Ca2+ by chelation with EGTA. Only additional chelation of Mg2+ with EDTA reduces the tyrosine fluorescence intensity. 4. Comparison of the Ca2+-binding parameters of phosphorylase kinase, which were previously determined under identical experimental conditions [Kilimann and Heilmeyer (1977) Eur. J. Biochem. 73, 191 197], with those reported here on calmodulin isolated from this enzyme, allows the conclusion that Ca2+ binding to the holoenzyme occurs by binding to the delta subunit exclusively. 5. Ca2+ binding and Ca2+ activation of phosphorylase kinase are compared and discussed in relation to the Ca2+ and Mg2+-induced conformation changes of calmodulin. PMID- 6269845 TI - A cytochrome f/b6 complex of five polypeptides with plastoquinol-plastocyanin oxidoreductase activity from spinach chloroplasts. AB - The isolation of a cytochrome f/b6 complex from spinach chloroplasts, with high yield and purity is reported. The complex consists of five polypeptides with a molecular mass of 34, 33, 23.5, 20 and 17.5 kDa, and contains one cytochrome f, two cytochromes b6 and the Rieske Fe-S center with two non-heme irons. It does not contain plastocyanin and is almost completely devoid of chlorophyll and carotenoids, but lipid and detergent are present. It is lacking cytochrome b-559, although three of the five polypeptides seem to carry heme groups. The preparation has plastoquinol-plastocyanin oxidoreductase activity with plastoquinol-1 and plastoquinol-9, which is sensitive to 2,5 dibromomethylisopropyl-p-benzoquinone, to 2-iodo-6-isopropyl-3-methyl-2',4',4' trinitrodiphenyl ether, to 5-n-undecyl-6-hydroxy-4,7-dioxobenzothiazole, and to bathophenanthroline. Characteristics of this activity with respect to substrate concentrations, pH, detergent effect and other parameters are described. PMID- 6269846 TI - Purification and characterization of a specific histone H1 protein kinase from mouse plasmacytoma. AB - A protein kinase with high specificity for histone H1 was purified from a plasmacytoma microsomal fraction by a high-salt wash, ammonium sulfate precipitation, chromatography on DEAE-cellulose, hydroxyapatite and Sephadex G 200 columns, and the main properties of this kinase were studied. A sulfhydryl compound, such as 2-mercaptoethanol or dithiothreitol, was necessary for full activity. The optimum pH was 7.4-7.8. After purification, the histone H1 kinase was not stimulated by cAMP or cGMP. It was not inhibited by the heat-stable cAMP dependent protein kinase inhibitor from beef heart. It utilized preferentially GTP over ATP as phosphate donor. Km values for ATP and GTP were 58 microM and 1.4 microM respectively; the Km for histone H1 was 14 microgram ml-1. The molecular weight was approximately 90 000 by gel-exclusion chromatography. Analysis of the purified H1-specific protein kinase by polyacrylamide gel electrophoresis in dodecylsulfate showed two bands having molecular weights of approximately 64 000 and 54 000. Many characteristics of this kinase were similar to those of the chromatin-bound protein kinase reported by other workers in rapidly proliferating cells. PMID- 6269847 TI - Localization of the phosphoester bond hydrolyzed by the major apurinic/apyrmidinic endodeoxyribonuclease from rat-liver chromatin. AB - The major apurinic/apyrimidinic (AP) endodeoxyribonuclease from rat liver chromatin, an enzyme specific for AP sites in DNA, cleaves the phosphodiester bridge which is the immediate neighbour of the AP site on its 5' side leaving 3' hydroxyl and 5'-phosphate ends. In contrast with Escherichia coli endonuclease VI, this chromatin enzyme is inactive on reduced AP sites. PMID- 6269849 TI - Mossbauer spectroscopic studies of the nature of centre X of photosystem I reaction centres from the cyanobacterium Chlorogloea fritschii. AB - Reduced photosystem I samples, which give the electron paramagnetic resonance (EPR) signals associated with A, A and B, and A, B and X centres, have been studied using Mossbauer spectroscopy. The Mossbauer spectra obtained from each type of sample is different, which indicates that iron is associated with all three centres. The spectra are similar to those obtained from ferredoxins with 4Fe-4S centres and were fitted with oxidized and reduced components, the relative proportions depending on the degree of reduction of the sample as monitored by EPR. The sample which gave only the A EPR signal showed about 26% of the reduced component, the sample which gave A and B EPR signals showed about 48% of the reduced component, while the sample which gave A, B and X EPR signals showed about 65% of the reduced component. The measurements are consistent with X being a 4Fe-S4 centre. PMID- 6269848 TI - Receptor-mediated gonadotropin action in ovary. Possible regulatory role of cell surface sialic acid in gonadotropin interaction to purified bovine corpus luteum plasma membranes. PMID- 6269850 TI - Latent phosphorylase phosphatases from rat liver: relationship with the heat stable inhibitory protein. AB - A high-speed supernatant from rat liver contains at least two latent phosphorylase phosphatases the activities of which are revealed by treatment with ethanol, urea, mercaptoethanol or trypsin. This fraction also contains at least one protein which, after heating, inhibits to various degrees the activated form(s) of the two phosphatases. The two latent enzymes can be separated by cellulase-phosphate chromatography and can be differentiated by their preferential activation by ethanol or trypsin and by their different sensitivity to the inhibitory protein after ethanol activation. Activation of the latent phosphorylase phosphatases by ethanol, urea or mercaptoethanol is not accompanied by the destruction of the precursor of the inhibitory protein whereas activation by trypsin is. However, trypsin treatment of fractions previously activated by ethanol decreases their activity and also increases their sensitivity to the inhibitory protein in a way which is unrelated to the destruction of this inhibitor. Furthermore, some protein fractions, almost free of the precursor of the inhibitory protein can be readily activated by trypsin. In is concluded that the activation of the latent phosphorylase phosphorylase phosphatases is unrelated to the destruction of the inhibitory protein. PMID- 6269851 TI - Amino-acid sequence of the cytochrome c from the yeast Hansenula anomala. Identification of three methylated positions. AB - The cytochrome c of the yeast Hansenula anomala has been purified and sequenced. A combination of automatic and manual sequencing methods was used on the whole protein and on fragments obtained by cyanogen bromide cleavage and proteolytic fragmentation. The cytochrome presents an amino-terminal extension of six residues and the C-terminal one-residue deletion typical of plant and fungal cytochrome c. Lysines 72 and 73 are trimethylated, lysine 55 partly monomethylated and partly dimethylated. Positions 73 and 55 have never been found methylated before. PMID- 6269852 TI - Self-stabilization of the energy charge in a reconstituted enzyme system containing phosphofructokinase. AB - The self-stabilization of the energy charge and of ATP was investigated in an open reconstituted enzyme system containing phosphofructokinase, pyruvate kinase, adenylate kinase, and glucose-6-phosphate isomerase. The experiments were performed in a stirred flow-through reactor containing gel-entrapped enzymes. The dynamics of the system were analyzed theoretically by a model based on the kinetic properties of the individual enzymes. The energy charge was identified as one of the essential variables of the system. According to the theoretical prediction, homoeostasis of the energy charge was observed experimentally when either the maximal activity of phosphofructokinase, the energy charge of the influx solution of the flow rate through the reaction chamber was varied. It is shown that the efficiency of stabilization of the energy charge is related to the occurrence of alternative stationary states. PMID- 6269853 TI - Distribution of cyclic-GMP-dependent protein kinase in various rat tissues and cell lines determined by a sensitive and specific radioimmunoassay. AB - Cyclic-GMP-dependent protein kinase purified from bovine lung was radioiodinated by the Bolton-Hunter procedure yielding a specific radioactivity of 2200 Ci/mmol of enzyme, Using a specific precipitating rabbit antiserum to the cyclic-GMP dependent protein kinase, a sensitive radioimmunoassay was developed which can detect 200 pg (1.33 fmol) of cyclic GMP-dependent protein kinase. Immunoreactivity like that of cyclic-GMP-dependent protein kinase was detectable in extracts of all rat tissues tested, in extracts of cultured rat brain and heart cells, and in extracts of rat glioma (C6) and neuroblastoma x glioma hybrid cells. In extracts of several tissues and cell lines the presence of cyclic-GMP dependent protein kinase was also demonstrated by a photoaffinity-labeling procedure using 8-azidoinosine 3',5'-[32P]monophosphate. The results suggest that cyclic-GMP-dependent protein kinase is ubiquitously distributed although its level varies significantly from tissue to tissue and cell type to type. The results also support the hypothesis that cyclic-GMP-dependent protein kinase is involved in mediating some of the intracellular effects of those hormones, neurotransmitters and drugs which regulate the intracellular level of cyclic GMP. PMID- 6269855 TI - DNA topoisomerase I from mitochondria of Xenopus laevis oocytes. AB - Activity of DNA topoisomerase I has been characterized in extracts of mitochondria purified from Xenopus laevis oocytes. Several lines of evidence have been obtained for the intramitochondrial localization of the enzyme. The mitochondria-associated of DNA topoisomerase I represents 1% of the activity recovered from a total ovary population of oocytes. The enzymes has been purified by DEAE-cellulose, phosphocellulose and double-stranded DNA cellulose chromatography and its properties compared to those of its nuclear-cytosolic counterpart purified by the same purification steps. Both enzymes appear to possess very similar if not identical physico-chemical and catalytic properties. Neither enzyme shows DNA gyrase activity and they are both equally sensitive towards trypanocide drugs such as ethidium bromide and berenil. The mitochondrial enzyme is able to remove positive superhelical turns and possibly acts as a swivelase during replication of mitochondrial DNA. These results confirm the pioneering work of Fairfield et al. (1979, J Biol. Chem. 254, 9354) on the presence of a DNA topoisomerase I in mitochondria. However our results support the conclusion that in Xenopus laevis oocytes the mitochondrial and nuclear cytosolic DNA topoisomerase I are in all likelihood one and the same enzyme. PMID- 6269854 TI - Comparison of the NH2-Terminal sequences of chick Type I preprocollagen chains synthesized in an nRNA-dependent reticulocyte lysate. AB - RNA was extracted from 17-day-old chick embryo calvaria and translated by an mRNA dependent reticulocyte lysate. Procedures were developed for purifying intact pro alpha 1(I) and pro alpha 2 translation products from the lysate. These products were identified by comparing tryptic peptide elution patterns of the translation products with those obtained from secreted pro alpha chains. Partial sequence data from the amino terminus of each translation product demonstrated that each chain begins with a sequence that is different from that of the corresponding pro alpha chain, and that the two sequences are not the same. Also, the bacterial collagenase-resistant peptide from the amino terminus of prepro alpha 1(I) had an apparent molecular weight which was 10 000 greater than the peptide from pro alpha 1(I). PMID- 6269856 TI - Early events following the binding of epidermal growth factor to surface receptors on ovarian granulosa cells. AB - Receptors for epidermal growth factor (EGF) have been localized on the surface of ovarian granulosa cells using a colloidal gold avidin complex in conjunction with biotinylated EGF. On cells incubated at low temperature the receptors are predominantly monodisperse and have a random distribution. When cells are warmed to 37 degrees C the receptors aggregate into clusters. PMID- 6269858 TI - Skeletal scintigraphy in pachydermoperiostosis. PMID- 6269857 TI - Axenic Paramecium caudatum. III. Biochemical and physiological changes with culture age. AB - As Paramecium caudatum passes through the lag, log and stationary phases of the culture cycle, cellular protein content, polar (PL) and neutral (NL) lipid contents, marker enzyme activities, rate of digestive vacuole formation and cellular viability undergo characteristic changes. Maximal protein content (60 ng/cell) and enzyme activities ranging from 7 nmoles for catalase to 0.2 pmoles/cell/min for alkaline phosphatase were observed between days 2 and 4. This active metabolism paralleled the fine structure of 1 to 3 day-old cells which contained extensive foci of rough endoplasmic reticulum (RER) partially bordered by Golgi stacks and the rapid depletion of those lipid fields accumulated during day 1. Decrease in protein content and enzyme activities in late log phase indicated a slowing of cellular synthesis. The lipids in the medium were largely depleted and accounted for the low lipid uptake of 14 ng/cell on day 5 as compared with 615 ng/cell on day 1. Yet a vast amount of protein lysate was still available in the culture medium. During stationary phase, catalase activity remained constant, but activities of alkaline and acid phosphatases and 5'nucleotidase declined gradually to low levels, while those of Ca2+-ATPase and malate dehydrogenase declined precipitously. Only 25% of the maximal activities of the latter two enzymes remained by the end of stationary phase. A ten-fold increase in the cellular PL and NL content was already observed 24 h postinoculation. This accumulation was used for subsequent growth and cell divisions; PL declined exponentially and NL less steeply between days 1 and 6. PL remained level (5 ng/cell) throughout stationary phase while NL declined further to 1 ng/cell by day 11. The rate of digestive vacuole formation was constant (6.3 +/- 0.5 DV/5 min pulse) during the entire log phase, then declined from 4.4 on day 6 to 0.22 on day 11. When early to mid-stationary-phase cells were subcultured, some lag in growth was seen; a definite lag was observed when inoculating with late-stationary-phase cells. When early-death-phase cells were given fresh nutrients, many died; the surviving ones became fully rejuvenated after 48 h. The biochemical and physiological data from this study are correlated with the morphological study of the companion paper. PMID- 6269859 TI - Adrenomyeloneuropathy: demonstration of inclusions at the level of the peripheral nerve. AB - A patients is reported with a progressive neurological disease which started at the age of 19 years and included spasmodic paraplegia, urinary disorders, impotence and neuropathic signs. The neurological syndrome was associated with adrenal failure. The disease led to death within 5 years. In this characteristic picture of adrenomyeloneuropathy, biopsy of peripheral nerve disclosed lamellar inclusions in the Schwann cell cytoplasm. Such structures, which have already been observed in the sural nerve of some adrenoleukodystrophy cases reported previously, are described for the first time in a case of adrenomyeloneuropathy. PMID- 6269860 TI - Incidence of normocalcemic hyperparathyroidism in idiopathic hypercalciuria: evaluation by dietary calcium deprivation test. AB - Calcium metabolism was studied in 37 patients with "idiopathic hypercalciuria" on a home diet and after 10 days of low calcium dietary intake (less than 400 mg/24h). After low calcium intake, urinary calcium excretion returned to within normal limits in 70% of the cases. In the group of patients which failed to respond to calcium restriction, TmPO4/GFR values were reduced and, furthermore, in 20% of them plasma iPTH and urinary cAMP levels were increased. These data seem to indicate that: the incidence of absorptive hypercalciuria is higher than hypercalciuria of renal origin; normocalcemic hyperparathyroidism due to primary calcium leak is present only in a limited number of cases, consequently, hypercalciuria secondary to renal phosphate leak is a rather frequent occurrence. PMID- 6269861 TI - Genetic and antigenic requirements for induction of T helper cells for anti Sendai virus-specific antibody production. AB - T helper cells for the promotion of Sendai virus-specific antibody production were generated in vitro. They could be stimulated by infectious, UV light inactivated or fusion-negative Sendai virus, which had to be presented by adherent cells. Induction of T helper cells was virus-specific and required H-2 IA region compatibility between T cells and antigen-presenting cells. Delivery of help to B lymphocytes was neither virus-specific nor H-2-restricted. PMID- 6269862 TI - Effects of lectins on cAMP production and steroidogenesis in cultured adrenal tumor cells. PMID- 6269863 TI - Involvement of cAMP and cAMP-dependent protein kinase in the initiation of DNA synthesis by rat liver cells. PMID- 6269864 TI - The isolation of nuclei from tissue-cultured plant cells. PMID- 6269865 TI - Pellucid marginal corneal degeneration: a clinicopathologic study of two cases. PMID- 6269866 TI - Metabolism of benzo(a)pyrene in bovine lens epithelium. PMID- 6269867 TI - Change of nuclear protein phosphatase activity in the liver of old rats. PMID- 6269868 TI - Important factors in induction of long-term potentiation in thin hippocampal sections. PMID- 6269869 TI - Nervous system prophyrins in low-level peroral lead exposure. PMID- 6269870 TI - Effect of seizures kindled by subconvulsant doses of pentylenetetrazol on dopamine receptor binding and dopamine-sensitive adenylate cyclase in the rat. PMID- 6269871 TI - Effect of aminophylline on seizure thresholds and brain regional cyclic nucleotides in the rat. PMID- 6269872 TI - A distinct difference between slow and fast muscle in acetylcholinesterase recovery after reinnervation in the rat. PMID- 6269873 TI - Action of histamine and vasoactive intestinal peptide (VIP) on cyclic AMP in gastric glands isolated from human fetal stomach. AB - Histamine and VIP produce an elevation of cAMP production in gastric glands isolated from the human fetal stomach at 15 weeks gestation. These effects were attributed to the activation of 2 distinct receptor-cAMP systems, one being sensitive to histamine in parietal cells, and the other being sensitive to VIP in muco-peptic cell populations. The results suggest that histamine and VIP may play a role in inducing gastric secretion during fetal life in man. PMID- 6269874 TI - Effect of isoprenaline on dopamine receptors in the rabbit isolated renal artery. PMID- 6269875 TI - Angiotensin-converting enzyme and other enzymes in livers of mice with experimental schistosomiasis. PMID- 6269877 TI - Identity of the particulate form of calmodulin with soluble calmodulin. PMID- 6269876 TI - [Effect of opiate peptides on interneuronal transmission in the spinal cord]. AB - It has been shown that leucin- and methionine-enkephalins (200 microgram into the lateral brain ventricle), as well as synthetic opiate peptides FK 33-824 (2 mg/kg) and tetrapeptide (25 mg/kg) disturb the excitation transmission in the cat ventrolateral columns. The effects of opiate receptors was more pronounced in animals with the intact central nervous system as compared with spinal animals. Naloxone (1 mg/kg) eliminated the effect of opiate peptides. PMID- 6269878 TI - Selectivity of the Escherichia coli outer membrane porins ompC and ompF. PMID- 6269879 TI - Oxygen species in paraquat toxicity: the crypto-OH radical. PMID- 6269880 TI - The epinephrine-induced activation of the cardiac slow Ca2+ channel is mediated by the cAMP-dependent phosphorylation of calciductin, a 23 000 Mr sarcolemmal protein. PMID- 6269881 TI - The kinetics of the interaction between cyclic AMP and the regulatory moiety of protein kinase II. Evidence for interaction between the binding sites for cyclic AMP. PMID- 6269882 TI - The kinetics of association of cyclic AMP to the two types of binding sites associated with protein kinase II from bovine myocardium. PMID- 6269884 TI - Preparation of adrenocortical cell suspension highly responsive to ACTH or dibutyryl-cyclic AMP. Effects of albumin, Ca2+ or stress. PMID- 6269883 TI - Hexamethylphosphoric triamide as a solubilizing agent. Purification and reactivation of diglyceride kinase. PMID- 6269885 TI - Stimulation of enzyme activities by fragments of calmodulin. PMID- 6269887 TI - N-terminal sequence homology among retinoid-binding proteins from bovine retina. PMID- 6269886 TI - Leukotriene B4--a stereospecific stimulator for release of lysosomal enzymes from neutrophils. PMID- 6269888 TI - Inhibition of in vitro translation by antibodies directed against N6 methyladenosine. PMID- 6269889 TI - Disulfide bonds protect the encapsidated chromosomes of Simian virus 40. PMID- 6269890 TI - Subcellular distribution of cyclic AMP-dependent protein kinase activity and of cyclic AMP-binding proteins in human platelets. Modification by Ca2+-dependent proteolysis. PMID- 6269891 TI - Cloning of a defective polyoma DNA molecule with rearrangements in the region coding for middle and large T antigens. PMID- 6269892 TI - Conditions affecting DNA cleavage by TthI at a TthI endonuclease-dam methylase overlapping sequence. PMID- 6269894 TI - Phosphorylation of human and rat blood plasma proteins in vitro with cyclic 3',5' AMP-stimulated protein kinase and [32P]ATP. PMID- 6269893 TI - Inactivation of liver phosphofructokinase by phosphofructokinase phosphatase or by low pH is inhibited by fructose 2,6-bisphosphate. PMID- 6269895 TI - The recognition and redox properties of a component, possibly a quinone, which determines electron transfer rate in ubiquinone-cytochrome c oxidoreductase of mitochondria. PMID- 6269896 TI - Inhibitors of nuclear ADP-ribosyl transferase retard DNA repair after N-methyl-N nitroso-urea. Further evidence for the involvement of (ADP-ribose)n in DNA repair. PMID- 6269897 TI - The induction of ovarian LH-receptors by FSH is mediated by cyclic AMP. PMID- 6269898 TI - Two molecular forms of the isolated brain enzyme 2',3'-cyclic nucleotide 3' phosphodiesterase. PMID- 6269899 TI - Inversely related oscillations in the contents of cyclic GMP and the total adenine nucleotides in steady-state perfused rat hearts. PMID- 6269901 TI - Magnesium dependence of sarcoplasmic reticulum calcium transport. AB - The activity of the calcium transport systems in the sarcoplasmic reticulum membranes operating in the forward and reverse modes depends on the presence of magnesium ions. When the system operates as an NTP-driven calcium pump, magnesium enters the reaction chain chelated with NTP. Magnesium is a component of the NDP sensitive phosphoprotein species involved in the NDP-NTP exchange reaction. When the system operates in the reverse mode as a calcium efflux-driven NDP synthetase, magnesium together with inorganic phosphate rapidly forms the initial phosphorylated intermediate. The stability of the magnesium-phosphoprotein complex is considerably enhanced by an existing calcium gradient. Magnesium as well as calcium affects the partitioning of the energy in the reaction sequence. PMID- 6269900 TI - Glucocorticoids elevate the level of enkephalin-like peptides in neuroblastoma x glioma hybrid cells. PMID- 6269902 TI - Magnesium effects on activation of skinned fibers from striated muscle. AB - The intracellular Ca movements that control contraction and relaxation of striated muscle are regulated by the membrane potential and influenced by Mg2+. In skinned fibers, the internal composition can be manipulated directly by Ca movements estimated from isometric force transients, net changes in sarcoplasmic reticulum (SR) Ca, and 45Ca flux between fiber and bath. Stimulated Ca release, unlike unstimulated 45Ca efflux at low external [Ca2+], is highly [Mg2+] sensitive at 20 C. Force and tracer measurements indicate three major sites of Mg2+-Ca2+ interaction in situ: Mg2+ can stimulate the SR active Ca transport system, inhibit a Ca2+-dependent Ca efflux pathway of SR, and shift the force [Ca2+] relation, presumably by reducing Ca2+ binding to myofilament regulatory sites. These mechanisms constrain the resting Ca flux and are adaptive during relaxation. However, analysis of CI-stimulated 45Ca release and reaccumulation suggests that the depolarization process may inhibit Mg2+-dependent Ca influx, the membrane potential controlling both efflux and influx; recent studies on voltage-clamped cut fibers support this hypothesis. The Ca2+ and Mg2+ dependence of caffeine-stimulated 45Ca efflux suggests that Mg2+ inhibition of the Ca2+ dependent efflux pathway is small during rapid Ca2+ efflux. Therefore, both Mg2+ mechanisms, which minimize net release, may be reversed during normal activation. PMID- 6269903 TI - Anabolic steroids are fool's gold. AB - Since increases in muscle strength are proportional to increases in the cross sectional diameter of the muscles being trained, the body must convert greater than normal amounts of amino acids available to it to increase size in athletes in training. When androgens became available in the 1930's they were used primarily to restore positive nitrogen balance in victims of starvation. Anabolic steroids, which were developed to avoid unwanted effects of androgens, were first given to weight lifters, but football players and weight throwers were soon using them. From 1965 to 1977, 25 clinical studies were published dealing with the administration of an anabolic-androgenic steroid to adult human males for evaluating changes in strength and, in 10 of these studies, in maximum oxygen consumption. In 12 of these studies, improvements were claimed from the use of these steroids; in the other 13 no improvements were observed. Other studies have shown that in healthy adult males these steroids reduce testosterone and gonadotrophin output, which reduces spermatogenesis. Alterations of normal liver function have been found in up to 80% of persons treated with C17-alkylated testosterone derivatives. Peliosis hepatitis, with liver failure and death, and fatal liver cancer have also been reported in adults so treated. Reliable methods for detecting anabolic steroids in the urine are now used in certain international competitions. Testing, announced bans, and disqualifications have not been effective in controlling the use of the drugs. The best hope for doing so lies in continuing education of athletes and their supervisors. PMID- 6269904 TI - Ly 11.2: a cell surface antigen that may identify murine lymphocytes susceptible to transformation by oncogenic agents. PMID- 6269905 TI - Gestational outcome following hysteroscopic lysis of adhesions. AB - Thirty-eight infertile women conceived 43 times following treatment for intrauterine adhesions (IUA). Adhesions were classified as being minimal in 7 women, moderate in 20 others, and extensive in 11. All women underwent hysteroscopy with division of all adhesions utilizing miniature scissors and high dose estrogen treatment for 2 months. In addition 35 of the 38 women had either an intrauterine contraceptive device or a Foley catheter placed to prevent readherence of the walls, and 31 women had the uterine cavity investigated again prior to attempting a pregnancy. Prior to treatment for IUA only 16.7% of all pregnancies in those women with no other cause for pregnancy loss resulted in the delivery of a living infant. However, following treatment 87.2% of these pregnancies resulted in the delivery of a viable infant (P less than 0.001). No instances of placenta accreta occurred, and manual removal of the placenta was not required. Division of adhesions under hysteroscopic control together with the adjunctive measures utilized is superior to all other methods of therapy for IUA and should replace them. PMID- 6269906 TI - [Effect of ether anesthesia on Na+, K+ ATPase activity in different brain structures]. PMID- 6269907 TI - [Routes and mechanisms of the transmembrane entrance of calcium ions participating in the activation of contraction into smooth muscle cells]. PMID- 6269908 TI - [Transmission of information concerning image brightness by neurons of the lateral geniculate body in the cat]. AB - The response of the LGB neurons to moving stimuli consisting of 8 bars with stepwise increasing luminousness (by 0.47 lg units) revealed threshold intensities varying from neuron to neuron by 1.5--2.0 lg units. Frequency of the on- and off-central neurons activity depended on stimuli luminousness. Both on- and off-neurons increased their firing rate on increase of the stimuli luminousness. The probable mechanism of information transmission of the luminousness change (with constant contrast) and its place in the hypothesis of the point-to-point image description at the subcortical level of the visual system, are discussed. PMID- 6269909 TI - [Relation between midbrain auditory center neuronal responses and sound on-off time ratio in the frog]. AB - The EPs and unit activity of the frog midbrain auditory region were tested during 1,2,5 and 10/sec presentations of the tone bursts. The maximal amplitude of the EPs and the exaltation of unit activity occurred when the burst duration was in the range 10--30 msec. The elongation of the tone bursts led to the increase of the latency and the decrease of the maximal firing rate. The synaptic mechanisms of this suppression are discussed. PMID- 6269910 TI - [Role of ACTH and corticosteroids in the aggressive-defensive behavior of rats]. AB - Judging by the thresholds of the squeak, rising and fight reactions, the fight reaction frequency and threat standing reaction to shock--induced aggression in rats, the ACTH enhanced the fear response and fight behaviour both in normal and adrenalectomized rats. Removal of the adrenal glands facilitated the shock- induced aggression whereas hydrocortisone and DOCA caused the opposite effect. The ACTH seems to produce a direct extraadrenal effect on the brain structures thus inducing the formation of irritable aggression. PMID- 6269913 TI - [Kinetics of sodium currents in the membrane of Ranvier's nodes during de- and repolarization]. PMID- 6269912 TI - [Effect of neutral amino acids on neurons and synaptic transmission in the isolated rat spinal cord]. AB - GABA, glycine and beta-alanine depolarized motoneurons and primary afferents of the isolated spinal cord of rats of 10-14-day age. The blockade of synaptic transmission in the spinal cord by abundant Mg++ ions turns the depolarization into hyperpolarizing responses. Depolarization of the primary afferents evoked by glycine is antagonized by strychnine, picrotoxin reduces the GABA effects, and both convulsants diminish the beta-alanine effects. Neural amino acids reduce both ventral and dorsal root potentials. Strychnine and picrotoxin increase the amplitude and duration of ventral root potentials. Picrotoxin decreases the amplitude of dorsal root potentials. PMID- 6269911 TI - [Sensitivity of neurons in different regions of the brain to met-enkephalin, beta endorphin, and thyroliberin in the rat]. AB - The oligopeptides were microiontophoretically applied to neurons of the sensory cortex, hippocampus, thalamus and septum. Metenkephalin and beta-endorphin increased activity of some neurons while decreasing it in other cells. Nalorphine antagonized the inhibition effect of metenkephalin in all the brain areas under study. Inhibition of the peptide activating action occurred in hippocampal and septal neurons. A correlation between effects of metenkephalin and beta-endorphin on the same neurons was revealed in the cortex and thalamus. Thyroliberin mostly activated neurons in all the areas. Independence of neuronal effects of TRH and opioid peptides was obvious. PMID- 6269914 TI - [Possible model representations of the neurophysiologic mechanisms of analysis of the direction and rate of movement of a visual object]. PMID- 6269915 TI - [Symposia of the Japan Endocrine Society. Abstract]. PMID- 6269916 TI - [The direct effect of prostaglandin f2 alpha on corpus luteum in vitro (author's transl)]. PMID- 6269917 TI - [Studies on immunoreactive ACTH from human term placenta. (I) Detection of a high molecular weight-immunoreactive ACTH in term placenta (author's transl)]. AB - Extracts of human term placenta were fractionated by Sephadex G-75 gel filtration and assayed for immunoreactive ACTH. Both high and low molecular weight protein fractions were detected to be immunologically reactive toward anti-human ACTH (1- 39 alpha) antibody. For the extraction of low molecular weight ACTH from human term placenta (pl. -ACTH), a glacial acetic acid-acetone mixture was employed, while a pH 3.0-HCl solution was used for high molecular weight immunoreactive ACTH. The high molecular weight immunoreactive ACTH fraction (F-I), co-eluted with horse hemoglobin from a Sephadex G-75.column in 0.1M acetic acid, was essentially devoid of low molecular weight materials as revealed by polyacrylamide gel disc electrophoresis at pHs 9.5 and 4.3. Tryptic digestion of F-1 at pH 8.1 and 37 degrees C for 4 hr with E/S of 1/100, followed by fractionation with a Sephadex G-75, resulted in the formation of lower molecular weight fragments. One fragment was eluted at the same position as that of porcine ACTH with a recovery of 86% of immunoreactivity of F-I. Another fragment which was eluted last exhibited positive beta-endorphin receptor binding activity. These results suggest the presence of a common precursor protein to ACTH and beta endorphin in human term placenta. PMID- 6269918 TI - [Plasma 11-deoxycortisol response to single dose metyrapone in prostatic cancer patients (author's transl)]. AB - A radioimmunoassay procedure for plasma 11-deoxycortisol (S) was developed using an antiserum prepared by immunizing rabbits with S-21-hemisuccinate bovine serum albumin and S-3-oxime-bovine serum albumin. Thereafter plasma S, cortisol (F) and adrenocorticotropic hormone (ACTH) responses to metyrapone were investigated in 13 normal adult males and 39 patients with prostatic cancer. The results were as follows: 1) The antiserum against S-3-oxime-bovine serum albumin had less cross reactivity (less than 10%) with other steroids than that against S-21 hemisuccinate bovine serum albumin and obtained a good standard curve. The intra assay variance and interassay variance of this method using the former antiserum (N = 10) were 12.4% asd 14.9% respectively, and the blank value was 3.7 +/- 1.6 pg. 2) Basal levels of S. F and ACTH in plasma from 13 normal adult males, ranged 21 approximately 80 years, old, were 98.4 +/- 15.7 ng/dl (mean value +/- S.E.), 12.7 +/- 0.78 micrograms/dl and 30.6 +/- 3.02 pg/ml respectively. Those level increased to 7060 +/- 598 ng/dl, 24.3 +/- 1.69 micrograms/dl and 24.3 +/- 1.6 pg/ml at 9 a.m. following oral administration of metyrapone (30 mg/kg b.w.) at midnight. 3) Both basal levels and responses of plasma S and F to metyrapone increased remarkably, while those of ACTH were within the normal range in prostatic cancer patients during the estrogen therapy. It was considered that protein-bound S and F increased following elevation of corticosteroid binding globulin but returned to the normal range about 2 weeks after discontinuation of the therapy. 4) In case treated wih estrogens, plasma, S, F and AC normal range in prostatic cancer patients during the estrogen therapy. It was considered that protein-bound S and F increased following elevation of corticosteroid binding globulin but returned to the normal range about 2 weeks after discontinuation of the therapy. 4) In case treated wih estrogens, plasma, S, F and AC normal range in prostatic cancer patients during the estrogen therapy. It was considered that protein-bound S and F increased following elevation of corticosteroid binding globulin but returned to the normal range about 2 weeks after discontinuation of the therapy. 4) In case treated wih estrogens, plasma, S, F and ACTH responses to metyrapone were unchanged compared to normal adult males 2 approximately 4 weeks after discontinuation of the therapy, and this data suggested that estrogens had no inhibitory effect on the pituitary-adrenal axis. However, in cases treated with progestational agents over a long-term period, plasma S and ACTH responses to metyrapone decreased slightly but returned to the normal range 2 approximately 4 weeks after discontinuation of the therapy. This suggested that the inhibitory effect of these agents on the pituitary-adrenal axis was mild and reversible. PMID- 6269919 TI - Necrolytic migratory erythema associated with an islet cell tumour of the pancreas. AB - A man of 59 is described with a characteristic skin eruption, necrolytic migratory erythema, associated with a malignant islet cell pancreatic tumour. There was no definite evidence that this was a glucagonoma although previous reports have suggested that the pancreatic tumour usually associated with necrolytic migratory erythema is always a glucagonoma. The relevant literature is reviewed. PMID- 6269920 TI - Hormone-stimulated metabolism of inositol lipids and its relationship to hepatic receptor function. PMID- 6269921 TI - Cyclic AMP- and Ca2+-dependent protein kinases and their concerted effects on Ca2+ fluxes. PMID- 6269922 TI - Cyclic AMP in cervical mucus. AB - Cyclic adenosine monophosphate normally stimulates motility of spermatozoa. Its concentration in cervical mucus was studied by an isotopic competitive method in 15 normal women aged between 20 and 50 years. Values were very high, particularly in the periovulatory period, with a mean (+/-SD) value of 167.90 +/- 154.96 nmol/l. These are very high when compared with values in other biological fluids (blood serum and urine). PMID- 6269923 TI - Molecular mechanisms involved in alpha-adrenergic responses. PMID- 6269924 TI - Some characteristics of GnRH receptors in rat-pituitary membranes: differences between an agonist and and antagonist. AB - The interaction of gonadotropin-releasing hormone (GnRH) agonists and antagonists with pituitary membranes was studied by using 125I-labeled agonist, [D-Ser(t Bu)6, des-Gly10-ethylamide]-GnRH, and antagonist [D-pGlu1, D-Phe2, Trp3,6]-GnRH. Their binding was affected differently by cations, and by pretreatment of membranes with proteolytic enzymes and sulfhydryl-blocking reagents. Monovalent cations at millimolar concentrations (10-100 mM) and divalent cations at lower concentrations (0.5-5 mM) reduced more significantly the binding of the agonist than that of the antagonist. Pretreatment of the membranes with trypsin and chymotrypsin abolished the specific binding of both agonist and antagonist, in a dose-response manner, with the former being less affected. Pretreatment of the membranes with sulfhydryl-blocking reagents did not alter the binding of the antagonist but enhanced the binding of the agonist. This enhancement in the specific binding was found to be due to an increase in the apparent affinity of the agonist. These results may suggest that GnRH agonists and antagonists bind differently to the same receptor. PMID- 6269925 TI - Steroid-induced proteins in human endometrium. AB - The synthesis of soluble proteins in human endometria at various phases of menstrual cycle was evaluated by polyacrylamide gel electrophoresis of [35S]methionine-labeled proteins. Densitometric analysis of the gels revealed alterations in the rate of synthesis of single protein bands throughout the cycle. Administration of conjugated estrogens (Premarin) to women undergoing hysterectomy, or exposure, in vitro, of the endometrial tissue to 17 beta estradiol produced an increased incorporation of [35S]methionine into a specific protein which migrated on SDS-polyacrylamide gels at a molecular weight of about 55 000. Induction of this protein was observed only in those endometria showing a secretory histological appearance. The protein was resolved into at least 2 different spots in two-dimensional gel electrophoresis. An increase in the rate of synthesis of another endometrial protein with an apparent molecular weight of 51 000 was observed in tissues exposed in vitro to medroxyprogesterone acetate. These steroid-induced proteins may be a useful marker for studying hormone action in both normal and neoplastic endometria. PMID- 6269926 TI - Characterization of a bone-specific alkaline phosphatase in chick limb mesenchymal cell cultures. PMID- 6269927 TI - The development of hormonal responses of cultured embryonic chick limb mesenchymal cells. PMID- 6269928 TI - Cytoplasmic inclusions specific to the sea urchin germ line. PMID- 6269929 TI - Quantitation of the accumulation of histone messenger RNA during oogenesis in Xenopus laevis. PMID- 6269930 TI - Isolation of cloned genes differentially expressed at early and late stages of Drosophila embryonic development. PMID- 6269931 TI - The cuticle of Caenorhabditis elegans. II. Stage-specific changes in ultrastructure and protein composition during postembryonic development. PMID- 6269932 TI - Fertilization of sea urchin eggs is accompanied by 40 S ribosomal subunit phosphorylation. PMID- 6269933 TI - The genesis and transmission of epidermal potentials in an amphibian embryo. PMID- 6269934 TI - Interactions between dissociated rat sympathetic neurons and skeletal muscle cells developing in cell culture. I. Cholinergic transmission. PMID- 6269935 TI - Timolol treatment in the irritable bowel syndrome. AB - The overall effect of the beta-blocker timolol maleate was not significantly different from placebo in patients with the irritable bowel syndrome on a high fibre diet. However, all 3 symptom-free patients were on timolol maleate. If beta blockers have a major role to play in the treatment of the irritable bowel syndrome it must be through a central rather than a peripheral effect. PMID- 6269937 TI - [Sensitivity, to cefotaxime (HR 756), of multiresistant bacteria and/or beta lactamase producers]. PMID- 6269939 TI - Lactate dehydrogenase isozyme patterns of normal human fibroblasts and their in vitro-transformed counterparts obtained by treatment with CO-60 gamma-rays, SV40 or 4-nitroquinoline 1-oxide. AB - Lactate dehydrogenase (LDH) isoenzyme patterns of normal human fibroblasts and their in vitro-transformed counterparts were studied. Normal human fibroblasts were derived from embryonic or adult skin or embryonic lung tissues. These cells were transformed into neoplastic cells having unlimited growth potential and abnormal karyotypes by treatment with CO-60 gamma-rays, SV40 or 4-nitroquinoline 1-oxide. No significant difference in LDH isoenzyme patterns was observed in growing or confluent cultures, in the process of in vitro aging of normal human fibroblasts, or in embryonic or adult skin fibroblasts, but there was a considerable difference in isozyme patterns between lung and skin fibroblasts cultured from embryos. All of the transformed fibroblast cell lines derived from lung or skin showed a distinctly increased ratio of B to A subunit (greater than 0.5), whereas normal human fibroblasts did not (less than 0.5). There was no significant difference in total activity of LDH in the various cells used for the present experiments. These findings suggest that the changes of LDH isozyme patterns may be useful as a marker of neoplastic transformation in cultures of normal human fibroblasts. PMID- 6269938 TI - Geographical pathology of gastric carcinoma: a comparative study on histological types between high and low mortality areas in Japan. AB - A histological comparison of 1,687 cases of gastric carcinoma in Niigata, a high mortality prefecture for this cancer, and 954 cases in Kagoshima, a low mortality area, was carried out in order to investigate whether or not this difference in mortality reflects any change of histological type of gastric carcinoma. In both series, in both males and females , the proportion of adenocarcinoma increased with increase of the patients' age, while that of diffuse carcinoma decreased. When data from the two prefectures were compared, there was no significant difference in age group distribution of each histological type. It appears that the same histological types of gastric carcinoma occur throughout Japan. PMID- 6269940 TI - Cyclic nucleotide response to acid-secreting stimuli in guinea pig gastric mucosa in vitro. AB - To investigate the mechanism of intracellular transmission of three representative stimuli for gastric acid secretion, the dose-response relations of cyclic nucleotides accompanied by acid secretion stimulated by histamine, pentagastrin and bethanechol were comparatively studied using an in vitro preparation of guinea pig gastric mucosa surviving with a constant potential difference and acid secretion sensitive to amytal. The following results were obtained. (1) Both histamine- and pentagastrin-stimulated acid secretion accompanied a significant increase in cyclic AMP contents in the gastric mucosa and in the serosal solution without any increase in cyclic GMP. However, the ratio of the increase in acid secretion to that in cAMP content was significantly greater with pentagastrin than with histamine, indicating that pentagastrin exerts its acid-secreting stimulus with less increase in cyclic AMP. (2) Stimulation with bethanechol resulted in a significant increase in the mucosal cyclic GMP content without any change in cyclic AMP. From these findings, it has been concluded that the above three stimuli were transmitted differently in the target cells, presenting evidence against the common final mediator theory of histamine for gastric acid secretion. PMID- 6269936 TI - A partial view of the mechanism of insulin action. PMID- 6269941 TI - Killer cell (K-cell) population in chronic liver disease. AB - Peripheral blood killer cell (K-cell) population of patients with chronic hepatitis was investigated by means of a plaque-assay method using sheep red blood cells. The mean K-cell population of 14 control subjects was 5.1 +/- 2.0% (mean +/- SD), and that of 28 patients with chronic hepatitis was 4.4 +/- 3.1%. These 28 patients were divided into three groups: CPH, CAH 2A and CAH 2B. The mean K-cell population of each group was decreased in order of the severity of the disease. Especially, that of patients with CAH 2B was a statistically significant decrease (p less than 0.01) from control subjects. In the course most patients with CAH, K-cell population did not change for three months after admission. K-cell population was observed to decrease in the patients with active stage of liver cirrhosis, but not in patients with the terminal stage of liver cirrhosis, even in hepatoma patients. It is suggested that the K-cell population may play an important role of pathogenesis of chronic hepatitis. PMID- 6269942 TI - Age specific prevalence of anti HA in Japan--from multi-institutional analysis. AB - In order to estimate age specific prevalence of Anti HA in Japan, 1757 serum samples from healthy subjects or patients with nonhepatic disease taken in 6 different districts of Japan were tested for Anti HA using HAVAB Kit. Very low prevalence, less than 10%, was observed in young adults or children. These facts indicate the young Japanese are quite susceptible to HAV infection and the effective preventive measures are urgently needed. Over all prevalence of Anti HA was 56.2%. Comparing the age specific prevalence of Anti HA in Japan with those in other countries, the situation in Japan was in intermediate between highly endemic South-East region and developed European countries. PMID- 6269943 TI - Chronic inflammatory bowel disease: absence of adenovirus DNA as established by molecular hybridization.